1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
1026
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
1047
1048
1049
1050
1051
1052
1053
1054
1055
1056
1057
1058
1059
1060
1061
1062
1063
1064
1065
1066
1067
1068
1069
1070
1071
1072
1073
1074
1075
1076
1077
1078
1079
1080
1081
1082
1083
1084
1085
1086
1087
1088
1089
1090
1091
1092
1093
1094
1095
1096
1097
1098
1099
1100
1101
1102
1103
1104
1105
1106
1107
1108
1109
1110
1111
1112
1113
1114
1115
1116
1117
1118
1119
1120
1121
1122
1123
1124
1125
1126
1127
1128
1129
1130
1131
1132
1133
1134
1135
1136
1137
1138
1139
1140
1141
1142
1143
1144
1145
1146
1147
1148
1149
1150
1151
1152
1153
1154
1155
1156
1157
1158
1159
1160
1161
1162
1163
1164
1165
1166
1167
1168
1169
1170
1171
1172
1173
1174
1175
1176
1177
1178
1179
1180
1181
1182
1183
1184
1185
1186
1187
1188
1189
1190
1191
1192
1193
1194
1195
1196
1197
1198
1199
1200
1201
1202
1203
1204
1205
1206
1207
1208
1209
1210
1211
1212
1213
1214
1215
1216
1217
1218
1219
1220
1221
1222
1223
1224
1225
1226
1227
1228
1229
1230
1231
1232
1233
1234
1235
1236
1237
1238
1239
1240
1241
1242
1243
1244
1245
1246
1247
1248
1249
1250
1251
1252
1253
1254
1255
1256
1257
1258
1259
1260
1261
1262
1263
1264
1265
1266
1267
1268
1269
1270
1271
1272
1273
1274
1275
1276
1277
1278
1279
1280
1281
1282
1283
1284
1285
1286
1287
1288
1289
1290
1291
1292
1293
1294
1295
1296
1297
1298
1299
1300
1301
1302
1303
1304
1305
1306
1307
1308
1309
1310
1311
1312
1313
1314
1315
1316
1317
1318
1319
1320
1321
1322
1323
1324
1325
1326
1327
1328
1329
1330
1331
1332
1333
1334
1335
1336
1337
1338
1339
1340
1341
1342
1343
1344
1345
1346
1347
1348
1349
1350
1351
1352
1353
1354
1355
1356
1357
1358
1359
1360
1361
1362
1363
1364
1365
1366
1367
1368
1369
1370
1371
1372
1373
1374
1375
1376
1377
1378
1379
1380
1381
1382
1383
1384
1385
1386
1387
1388
1389
1390
1391
1392
1393
1394
1395
1396
1397
1398
1399
1400
1401
1402
1403
1404
1405
1406
1407
1408
1409
1410
1411
1412
1413
1414
1415
1416
1417
1418
1419
1420
1421
1422
1423
1424
1425
1426
1427
1428
1429
1430
1431
1432
1433
1434
1435
1436
1437
1438
1439
1440
1441
1442
1443
1444
1445
1446
1447
1448
1449
1450
1451
1452
1453
1454
1455
1456
1457
1458
1459
1460
1461
1462
1463
1464
1465
1466
1467
1468
1469
1470
1471
1472
1473
1474
1475
1476
1477
1478
1479
1480
1481
1482
1483
1484
1485
1486
1487
1488
1489
1490
1491
1492
1493
1494
1495
1496
1497
1498
1499
1500
1501
1502
1503
1504
1505
1506
1507
1508
1509
1510
1511
1512
1513
1514
1515
1516
1517
1518
1519
1520
1521
1522
1523
1524
1525
1526
1527
1528
1529
1530
1531
1532
1533
1534
1535
1536
1537
1538
1539
1540
1541
1542
1543
1544
1545
1546
1547
1548
1549
1550
1551
1552
1553
1554
1555
1556
1557
1558
1559
1560
1561
1562
1563
1564
1565
1566
1567
1568
1569
1570
1571
1572
1573
1574
1575
1576
1577
1578
1579
1580
1581
1582
1583
1584
1585
1586
1587
1588
1589
1590
1591
1592
1593
1594
1595
1596
1597
1598
1599
1600
1601
1602
1603
1604
1605
1606
1607
1608
1609
1610
1611
1612
1613
1614
1615
1616
1617
1618
1619
1620
1621
1622
1623
1624
1625
1626
1627
1628
1629
1630
1631
1632
1633
1634
1635
1636
1637
1638
1639
1640
1641
1642
1643
1644
1645
1646
1647
1648
1649
1650
1651
1652
1653
1654
1655
1656
1657
1658
1659
1660
1661
1662
1663
1664
1665
1666
1667
1668
1669
1670
1671
1672
1673
1674
1675
1676
1677
1678
1679
1680
1681
1682
1683
1684
1685
1686
1687
1688
1689
1690
1691
1692
1693
1694
1695
1696
1697
1698
1699
1700
1701
1702
1703
1704
1705
1706
1707
1708
1709
1710
1711
1712
1713
1714
1715
1716
1717
1718
1719
1720
1721
1722
1723
1724
1725
1726
1727
1728
1729
1730
1731
1732
1733
1734
1735
1736
1737
1738
1739
1740
1741
1742
1743
1744
1745
1746
1747
1748
1749
1750
1751
1752
1753
1754
1755
1756
1757
1758
1759
1760
1761
1762
1763
1764
1765
1766
1767
1768
1769
1770
1771
1772
1773
1774
1775
1776
1777
1778
1779
1780
1781
1782
1783
1784
1785
1786
1787
1788
1789
1790
1791
1792
1793
1794
1795
1796
1797
1798
1799
1800
1801
1802
1803
1804
1805
1806
1807
1808
1809
1810
1811
1812
1813
1814
1815
1816
1817
1818
1819
1820
1821
1822
1823
1824
1825
1826
1827
1828
1829
1830
1831
1832
1833
1834
1835
1836
1837
1838
1839
1840
1841
1842
1843
1844
1845
1846
1847
1848
1849
1850
1851
1852
1853
1854
1855
1856
1857
1858
1859
1860
1861
1862
1863
1864
1865
1866
1867
1868
1869
1870
1871
1872
1873
1874
1875
1876
1877
1878
1879
1880
1881
1882
1883
1884
1885
1886
1887
1888
1889
1890
1891
1892
1893
1894
1895
1896
1897
1898
1899
1900
1901
1902
1903
1904
1905
1906
1907
1908
1909
1910
1911
1912
1913
1914
1915
1916
1917
1918
1919
1920
1921
1922
1923
1924
1925
1926
1927
1928
1929
1930
1931
1932
1933
1934
1935
1936
1937
1938
1939
1940
1941
1942
1943
1944
1945
1946
1947
1948
1949
1950
1951
1952
1953
1954
1955
1956
1957
1958
1959
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
2031
2032
2033
2034
2035
2036
2037
2038
2039
2040
2041
2042
2043
2044
2045
2046
2047
2048
2049
2050
2051
2052
2053
2054
2055
2056
2057
2058
2059
2060
2061
2062
2063
2064
2065
2066
2067
2068
2069
2070
2071
2072
2073
2074
2075
2076
2077
2078
2079
2080
2081
2082
2083
2084
2085
2086
2087
2088
2089
2090
2091
2092
2093
2094
2095
2096
2097
2098
2099
2100
2101
2102
2103
2104
2105
2106
2107
2108
2109
2110
2111
2112
2113
2114
2115
2116
2117
2118
2119
2120
2121
2122
2123
2124
2125
2126
2127
2128
2129
2130
2131
2132
2133
2134
2135
2136
2137
2138
2139
2140
2141
2142
2143
2144
2145
2146
2147
2148
2149
2150
2151
2152
2153
2154
2155
2156
2157
2158
2159
2160
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
2176
2177
2178
2179
2180
2181
2182
2183
2184
2185
2186
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
2198
2199
2200
2201
2202
2203
2204
2205
2206
2207
2208
2209
2210
2211
2212
2213
2214
2215
2216
2217
2218
2219
2220
2221
2222
2223
2224
2225
2226
2227
2228
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
2261
2262
2263
2264
2265
2266
2267
2268
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
2280
2281
2282
2283
2284
2285
2286
2287
2288
2289
2290
2291
2292
2293
2294
2295
2296
2297
2298
2299
2300
2301
2302
2303
2304
2305
2306
2307
2308
2309
2310
2311
2312
2313
2314
2315
2316
2317
2318
2319
2320
2321
2322
2323
2324
2325
2326
2327
2328
2329
2330
2331
2332
2333
2334
2335
2336
2337
2338
2339
2340
2341
2342
2343
2344
2345
2346
2347
2348
2349
2350
2351
2352
2353
2354
2355
2356
2357
2358
2359
2360
2361
2362
2363
2364
2365
2366
2367
2368
2369
2370
2371
2372
2373
2374
2375
2376
2377
2378
2379
2380
2381
2382
2383
2384
2385
2386
2387
2388
2389
2390
2391
2392
2393
2394
2395
2396
2397
2398
2399
2400
2401
2402
2403
2404
2405
2406
2407
2408
2409
2410
2411
2412
2413
2414
2415
2416
2417
2418
2419
2420
2421
2422
2423
2424
2425
2426
2427
2428
2429
2430
2431
2432
2433
2434
2435
2436
2437
2438
2439
2440
2441
2442
2443
2444
2445
2446
2447
2448
2449
2450
2451
2452
2453
2454
2455
2456
2457
2458
2459
2460
2461
2462
2463
2464
2465
2466
2467
2468
2469
2470
2471
2472
2473
2474
2475
2476
2477
2478
2479
2480
2481
2482
2483
2484
2485
2486
2487
2488
2489
2490
2491
2492
2493
2494
2495
2496
2497
2498
2499
2500
2501
2502
2503
2504
2505
2506
2507
2508
2509
2510
2511
2512
2513
2514
2515
2516
2517
2518
2519
2520
2521
2522
2523
2524
2525
2526
2527
2528
2529
2530
2531
2532
2533
2534
2535
2536
2537
2538
2539
2540
2541
2542
2543
2544
2545
2546
2547
2548
2549
2550
2551
2552
2553
2554
2555
2556
2557
2558
2559
2560
2561
2562
2563
2564
2565
2566
2567
2568
2569
2570
2571
2572
2573
2574
2575
2576
2577
2578
2579
2580
2581
2582
2583
2584
2585
2586
2587
2588
2589
2590
2591
2592
2593
2594
2595
2596
2597
2598
2599
2600
2601
2602
2603
2604
2605
2606
2607
2608
2609
2610
2611
2612
2613
2614
2615
2616
2617
2618
2619
2620
2621
2622
2623
2624
2625
2626
2627
2628
2629
2630
2631
2632
2633
2634
2635
2636
2637
2638
2639
2640
2641
2642
2643
2644
2645
2646
2647
2648
2649
2650
2651
2652
2653
2654
2655
2656
2657
2658
2659
2660
2661
2662
2663
2664
2665
2666
2667
2668
2669
2670
2671
2672
2673
2674
2675
2676
2677
2678
2679
2680
2681
2682
2683
2684
2685
2686
2687
2688
2689
2690
2691
2692
2693
2694
2695
2696
2697
2698
2699
2700
2701
2702
2703
2704
2705
2706
2707
2708
2709
2710
2711
2712
2713
2714
2715
2716
2717
2718
2719
2720
2721
2722
2723
2724
2725
2726
2727
2728
2729
2730
2731
2732
2733
2734
2735
2736
2737
2738
2739
2740
2741
2742
2743
2744
2745
2746
2747
2748
2749
2750
2751
2752
2753
2754
2755
2756
2757
2758
2759
2760
2761
2762
2763
2764
2765
2766
2767
2768
2769
2770
2771
2772
2773
2774
2775
2776
2777
2778
2779
2780
2781
2782
2783
2784
2785
2786
2787
2788
2789
2790
2791
2792
2793
2794
2795
2796
2797
2798
2799
2800
2801
2802
2803
2804
2805
2806
2807
2808
2809
2810
2811
2812
2813
2814
2815
2816
2817
2818
2819
2820
2821
2822
2823
2824
2825
2826
2827
2828
2829
2830
2831
2832
2833
2834
2835
2836
2837
2838
2839
2840
2841
2842
2843
2844
2845
2846
2847
2848
2849
2850
2851
2852
2853
2854
2855
2856
2857
2858
2859
2860
2861
2862
2863
2864
2865
2866
2867
2868
2869
2870
2871
2872
2873
2874
2875
2876
2877
2878
2879
2880
2881
2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2911
2912
2913
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
2944
2945
2946
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
2977
2978
2979
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
3010
3011
3012
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3043
3044
3045
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
3076
3077
3078
3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
3109
3110
3111
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
3142
3143
3144
3145
3146
3147
3148
3149
3150
3151
3152
3153
3154
3155
3156
3157
3158
3159
3160
3161
3162
3163
3164
3165
3166
3167
3168
3169
3170
3171
3172
3173
3174
3175
3176
3177
3178
3179
3180
3181
3182
3183
3184
3185
3186
3187
3188
3189
3190
3191
3192
3193
3194
3195
3196
3197
3198
3199
3200
3201
3202
3203
3204
3205
3206
3207
3208
3209
3210
3211
3212
3213
3214
3215
3216
3217
3218
3219
3220
3221
3222
3223
3224
3225
3226
3227
3228
3229
3230
3231
3232
3233
3234
3235
3236
3237
3238
3239
3240
3241
3242
3243
3244
3245
3246
3247
3248
3249
3250
3251
3252
3253
3254
3255
3256
3257
3258
3259
3260
3261
3262
3263
3264
3265
3266
3267
3268
3269
3270
3271
3272
3273
3274
3275
3276
3277
3278
3279
3280
3281
3282
3283
3284
3285
3286
3287
3288
3289
3290
3291
3292
3293
3294
3295
3296
3297
3298
3299
3300
3301
3302
3303
3304
3305
3306
3307
3308
3309
3310
3311
3312
3313
3314
3315
3316
3317
3318
3319
3320
3321
3322
3323
3324
3325
3326
3327
3328
3329
3330
3331
3332
3333
3334
3335
3336
3337
3338
3339
3340
3341
3342
3343
3344
3345
3346
3347
3348
3349
3350
3351
3352
3353
3354
3355
3356
3357
3358
3359
3360
3361
3362
3363
3364
3365
3366
3367
3368
3369
3370
3371
3372
3373
3374
3375
3376
3377
3378
3379
3380
3381
3382
3383
3384
3385
3386
3387
3388
3389
3390
3391
3392
3393
3394
3395
3396
3397
3398
3399
3400
3401
3402
3403
3404
3405
3406
3407
3408
3409
3410
3411
3412
3413
3414
3415
3416
3417
3418
3419
3420
3421
3422
3423
3424
3425
3426
3427
3428
3429
3430
3431
3432
3433
3434
3435
3436
3437
3438
3439
3440
3441
3442
3443
3444
3445
3446
3447
3448
3449
3450
3451
3452
3453
3454
3455
3456
3457
3458
3459
3460
3461
3462
3463
3464
3465
3466
3467
3468
3469
3470
3471
3472
3473
3474
3475
3476
3477
3478
3479
3480
3481
3482
3483
3484
3485
3486
3487
3488
3489
3490
3491
3492
3493
3494
3495
3496
3497
3498
3499
3500
3501
3502
3503
3504
3505
3506
3507
3508
3509
3510
3511
3512
3513
3514
3515
3516
3517
3518
3519
3520
3521
3522
3523
3524
3525
3526
3527
3528
3529
3530
3531
3532
3533
3534
3535
3536
3537
3538
3539
3540
3541
3542
3543
3544
3545
3546
3547
3548
3549
3550
3551
3552
3553
3554
3555
3556
3557
3558
3559
3560
3561
3562
3563
3564
3565
3566
3567
3568
3569
3570
3571
3572
3573
3574
3575
3576
3577
3578
3579
3580
3581
3582
3583
3584
3585
3586
3587
3588
3589
3590
3591
3592
3593
3594
3595
3596
3597
3598
3599
3600
3601
3602
3603
3604
3605
3606
3607
3608
3609
3610
3611
3612
3613
3614
3615
3616
3617
3618
3619
3620
3621
3622
3623
3624
3625
3626
3627
3628
3629
3630
3631
3632
3633
3634
3635
3636
3637
3638
3639
3640
3641
3642
3643
3644
3645
3646
3647
3648
3649
3650
3651
3652
3653
3654
3655
3656
3657
3658
3659
3660
3661
3662
3663
3664
3665
3666
3667
3668
3669
3670
3671
3672
3673
3674
3675
3676
3677
3678
3679
3680
3681
3682
3683
3684
3685
3686
3687
3688
3689
3690
3691
3692
3693
3694
3695
3696
3697
3698
3699
3700
3701
3702
3703
3704
3705
3706
3707
3708
3709
3710
3711
3712
3713
3714
3715
3716
3717
3718
3719
3720
3721
3722
3723
3724
3725
3726
3727
3728
3729
3730
3731
3732
3733
3734
3735
3736
3737
3738
3739
3740
3741
3742
3743
3744
3745
3746
3747
3748
3749
3750
3751
3752
3753
3754
3755
3756
3757
3758
3759
3760
3761
3762
3763
3764
3765
3766
3767
3768
3769
|
The Project Gutenberg EBook of A Statistical Inquiry Into the Nature and
Treatment of Epilepsy, by Alexander Hughes Bennett
This eBook is for the use of anyone anywhere at no cost and with
almost no restrictions whatsoever. You may copy it, give it away or
re-use it under the terms of the Project Gutenberg License included
with this eBook or online at www.gutenberg.org
Title: A Statistical Inquiry Into the Nature and Treatment of Epilepsy
Author: Alexander Hughes Bennett
Release Date: June 20, 2011 [EBook #36474]
Language: English
Character set encoding: ASCII
*** START OF THIS PROJECT GUTENBERG EBOOK STATISTICAL INQUIRY--EPILEPSY ***
Produced by Bryan Ness, Leonard Johnson and the Online
Distributed Proofreading Team at https://www.pgdp.net (This
book was produced from scanned images of public domain
material from the Google Print project.)
A STATISTICAL INQUIRY
INTO
THE NATURE AND TREATMENT
OF
EPILEPSY
BY
A. HUGHES BENNETT, M.D.,
PHYSICIAN TO THE HOSPITAL FOR EPILEPSY AND PARALYSIS, AND
ASSISTANT PHYSICIAN TO THE WESTMINSTER HOSPITAL.
LONDON
H. K. LEWIS, 136, GOWER STREET, W.C.
1884.
These three papers have already appeared in the Medical Journals, at
different dates, during the past few years. They are now republished
together, so as to form a connected inquiry. Since the production of the
first and second of them, increased experience has greatly augmented the
clinical material which might have been utilised in their investigation:
but, as the essential facts have only thus been confirmed, and the
general conclusions arrived at have remained the same, it has been
thought best, with the exception of certain verbal alterations, to
preserve the text of the articles as they originally appeared.
A. H. B.
38, QUEEN ANNE STREET, W.
_May, 1884_
CONTENTS.
I.--AN INQUIRY INTO THE ETIOLOGY AND SYMPTOMATOLOGY OF EPILEPSY.
II.--AN INQUIRY INTO THE ACTION OF THE BROMIDES ON EPILEPTIC ATTACKS.
III.--AN INQUIRY INTO THE EFFECTS OF THE PROLONGED ADMINISTRATION OF
THE BROMIDES IN EPILEPSY.
I.
AN ENQUIRY
INTO THE
ETIOLOGY AND SYMPTOMATOLOGY
OF EPILEPSY.[A]
The science of medicine is to be advanced by the careful collection of
well-recorded facts, rather than by general statements or unsupported
assertions. No inquiry thus conducted with scientific precision can fail
to be without value, and to add a mite to that store of positive
knowledge from which must emanate all hopes of progress for the healing
art. Our acquaintance with the nature of epilepsy is as yet in its
infancy, and although much valuable practical information has been put
on record regarding this disease, it is believed that the following
contribution may not be useless in either confirming or questioning
previous conclusions.
The clinical aspects of epilepsy are especially difficult to investigate
with exactitude. The physician, as a rule, is not himself a witness to
the chief phenomena characteristic of the disease. He is therefore
compelled, in most cases, to trust to the statements of the patient and
his friends for their description, and even when the cross-examination
is conducted with the greatest care, there are many points impossible to
ascertain with certainty. In the following cases of epilepsy, which have
been under my own care, those only are included in which loss of
consciousness formed the chief feature of the attack; and in the
succeeding particulars, attention will be specially directed to etiology
and symptomatology.
ETIOLOGY.
This may conveniently be discussed under (1) Predisposing causes, and
(2) Exciting causes.
1.--PREDISPOSING CAUSES.
_Sex and Sexual Conditions._--In one hundred unselected cases of
epilepsy there were--
Males, 47 per cent.
Females, 53 per cent.
showing that practically the sexes were affected in equal proportions.
Of the females there were--
Unmarried, 58.5 per cent.
Married, 41.5 per cent.
The greater number amongst the unmarried females is probably due to the
list including children, and also to the fact that epilepsy is not an
attraction to a man who purposes matrimony. Of the married females--
The attacks were uninfluenced by marriage in 68.1 per cent.
The attacks were diminished after marriage in 27.2 per cent.
The attacks were increased after marriage in 4.5 per cent.
Thus, in the majority of cases, marriage seems to have no influence on
the epileptic attacks of women, although in 27.2 per cent. the fits
appear to have been diminished after that ceremony.
Of the married females there were--
Children in 82.3 per cent.
No children in 17.6 per cent.
_Age._--In one hundred cases the age at which the first attack of
epilepsy took place will be seen from the following tables:--
Males. Females. Total.
From 1 to 10 years 9 14 23
From 10 to 20 years 11 23 34
From 20 to 30 years 14 9 23
From 30 to 40 years 10 6 16
From 40 to 50 years 1 0 1
From 50 to 60 years 2 1 3
It will thus be seen that, in males, the most prevalent period for the
first invasion of epilepsy is from the tenth to the thirtieth year; in
females, from the first to the twentieth year. In both sexes the disease
rarely commences after forty. The following table shows the ages of the
patients under observation:--
Males. Females. Total.
From 1 to 10 years 4 1 5
From 0 to 20 years 10 20 30
From 20 to 30 years 17 15 32
From 30 to 40 years 11 9 20
From 40 to 50 years 2 6 8
From 50 to 60 years 3 2 5
This indicates that cases of epilepsy comparatively rarely come under
observation after the age of forty. A large series of cases would
however be required to determine any definite conclusions as to the
mortality and longevity of the patients.
_Occupation and Profession._--These do not appear to have any special
relation to the production of epilepsy.
_Hereditary Tendency._--In each of the cases under observation a very
careful inquiry was made into the family history. This was confined to
the parents, grand parents, uncles, aunts, brothers, sisters, and
children of the patient. The following are the results:--
No family history of epilepsy, insanity, nervous or other hereditary
disorders in 59 per cent.
One or more members of family affected with one or more of the above
disorders in 41 per cent.
Of these last, in which there was a tainted hereditary history, one or
more members of the family suffered from--
Epilepsy in 63.4 per cent.
Insanity in 12.1 per cent.
Phthisis in 12.1 per cent.
Asthma in 2.4 per cent.
Apoplexy in 2.4 per cent.
Hysteria in 2.4 per cent.
Hemiplegia in 2.4 per cent.
Spinal complaint in 2.4 per cent.
Concerning the above table, it is to be remarked that frequently the
patient had several relatives suffering from different diseases; for
example, one with epilepsy, a second with insanity, and so on. In such a
case these have been classified under epilepsy, and, if this did not
exist, under insanity, or other afflictions in the above order.
Of those cases in which epilepsy was present in the family of the
patient, it existed in the following members:--
Father in 11.5 per cent.
Mother in 7.6 per cent.
Father, mother, and brother in 3.8 per cent.
Mother and child in 3.8 per cent.
Grandmother, mother, and two sisters in 3.8 per cent.
Mother and sister in 3.8 per cent.
Grandfather in 7.6 per cent.
Grandmother in 3.8 per cent.
Brother in 11.5 per cent.
Sister in 11.5 per cent.
Two brothers in 3.8 per cent.
Sister and child in 7.6 per cent.
Brother and uncle in 3.8 per cent.
Two uncles in 3.8 per cent.
Uncle in 3.8 per cent.
Aunt in 3.8 per cent.
Child in 3.8 per cent.
From these figures it will be seen that in no less than 41 per cent. of
the total number of cases there was a distinct family history of
hereditary disease. Of these no less than 87.5 per cent. were affections
of the nervous system, and 12.1 per cent. of phthisis. Of the former
63.4 per cent. had relatives afflicted with epilepsy, and 12.1 per cent.
with insanity. Epilepsy, according to these figures is eminently a
hereditary disease, and it is possible even to a greater extent than is
here represented; for the family history is often very difficult to
arrive at, in the class of persons on whom most of these observations
were made, who, either from ignorance or from prejudice, display a great
want of knowledge concerning the health of their ancestors.
_General health prior to the first attack._--As far as could be
ascertained this was--
Unimpaired in 90 per cent.
Delicate in 10 per cent.
By the term delicate is understood any chronic derangement of health.
The figures serve to indicate that, in the large majority of cases
epilepsy has no necessary connection with the impaired general health of
the patient.
_Special illnesses prior to the first attack._--There were--
No antecedent diseases in 78 per cent.
Antecedent diseases in 32 per cent.
Of these persons who, prior to the first attack of epilepsy, had
suffered from illnesses, the details are as follows:--
Convulsions at dentition in 43.7 per cent.
Rheumatic fever in 12.5 per cent.
Chorea in 6.2 per cent.
Mental derangement in 6.2 per cent.
Constant headache in 6.2 per cent.
Suppurating glands in 3.1 per cent.
Brain fever (?) in 3.1 per cent.
Small-pox in 3.1 per cent.
Typhus fever in 3.1 per cent.
Spinal curvature in 3.1 per cent.
Somnambulism in 3.1 per cent.
Scarlatina in 3.1 per cent.
The only special feature of this table is the fact that, of the cases of
epilepsy under observation, convulsions at dentition were positively
ascertained in 15 per cent. of the total number of cases, and in 43.7
per cent. of those having suffered from former illnesses. Here also the
percentage is probably in reality greater, as it is obvious that many of
the patients were ignorant as to whether or not these symptoms existed.
There is no evidence that any of the other illnesses had any relation to
the epilepsy.
_Temperance and Intemperance._--On this head nothing definite could be
ascertained. The patients either do not tell the truth, or have very
elastic notions as to moderation in the use of alcoholic stimuli.
2.--EXCITING CAUSES.
To ascertain the exciting causes of epileptic seizures with exactitude
is usually a matter of very great difficulty. It is simple enough when
the results directly follow the cause; but this is not commonly the
case. If, for example, a man, after a blow on the head (having been
previously in good health) becomes suddenly seized with epileptic
attacks within a few hours or days of the accident, we may fairly assume
that the injury has originated or developed his illness. But should the
seizure not supervene for some months or years afterwards, the external
wound having in the meantime completely recovered, there remains on this
question a considerable element of doubt. In the same way a patient
often attributes the attacks to a fright which may have occurred weeks
or months before they began; yet great care should be taken in accepting
such a statement: on the other hand, it should not be utterly ignored.
Again, if a person develops epilepsy after severe and prolonged domestic
trouble or affliction, how are we accurately to determine the relation
between the two? These difficulties render an exact method of
ascertaining the exciting causes almost impossible, and this can only be
approximated by a careful consideration of the entire history and
circumstances of the case. Taking these into consideration, the
following statements have been drawn up, in which only those conditions
are recorded, where from a review of the whole case a reasonable
relation was found to exist between cause and effect.
In a hundred unselected cases of epilepsy there were--
No apparent exciting cause in 43 per cent.
Possible exciting cause in 57 per cent.
Of the cases where a possible exciting cause was present, the following
is an analysis:--
Blow or injury to head in 28.1 per cent.
Uterine disorder in 22.8 per cent.
Domestic trouble in 15.7 per cent.
Disease of the nervous system in 8.7 per cent.
Fright in 5.2 per cent.
Depression in 5.2 per cent.
Pregnancy in 5.2 per cent.
Mental strain in 3.5 per cent.
Sunstroke in 3.5 per cent.
Emotion in 1.7 per cent.
Thus, in no fewer than 16 per cent. of the total number of cases, and
28.1 of those in which a possible exciting cause was present, did
epileptic seizures follow injuries to the head. Of the cases recorded
under uterine disorders, it must be stated that these conditions were as
much the accompaniments as the cause of epilepsy, the relations between
the two being as follows:--
Attacks occurring at menstrual periods in 61.5 per cent.
Attacks associated with irregular menstruation in 30.7 per cent.
Attacks associated with uterine disease in 7.6 per cent.
An attempt was made in twenty-two cases to ascertain whether, in women,
the age at which the epileptic attacks began had any relation to the
period at which the catamenia commenced, with the following results:--
Average age at which attacks began 14.6 years
Average age at which catamenia began 14.6 years
This shows singularly enough exactly the same figures, and serves to
point out, that in women, the earliest manifestation of puberty is a
decided exciting cause for epileptic attacks. It must however be stated
that, in the female epileptics, the attacks commenced before the age of
puberty in 16.9 per cent. of their numbers. Of the 8.7 per cent. of
cases included under the term "diseases of the nervous system," the
epilepsy was associated with hemiplegia in all.
SYMPTOMATOLOGY.
In a hundred unselected cases of epilepsy there were--
Epilepsia gravior in 62 per cent.
Epilepsia mitior in 10 per cent.
Epilepsia gravior and mitior in 28 per cent.
1.--EPILEPSIA GRAVIOR.
_Premonitory Symptoms._--In the cases in which epilepsia gravior was
present there were--
No premonitory symptoms in 34.4 per cent.
Premonitory symptoms in 65.5 per cent.
Of those cases in which there were symptoms premonitory to the attack,
there were--
General premonitory symptoms in 47.4 per cent.
Special Aurae in 72.8 per cent.
By _general premonitory_ symptoms are understood those morbid conditions
lasting for some hours or days before each attack, and of the cases
under consideration in which these were present, the following is an
analysis:--
Prolonged vertigo in 46.4 per cent.
Headache in 21.4 per cent.
Nervousness in 14.2 per cent.
Drowsiness in 3.5 per cent.
Faintness in 3.5 per cent.
Depression of spirits in 3.5 per cent.
Cramps in 3.5 per cent.
Numbness of extremities in 3.5 per cent.
Of the cases in which a _special aura_ preceded the attack, the details
are as follows (the special symptom in each case being sudden):--
Loss of sight in 2.3 per cent.
Loss of speech in 13.9 per cent.
Loss of hearing in 2.3 per cent.
General tremor in 16.2 per cent.
Tremor of one foot in 2.3 per cent.
Sensation in epigastrium in 6.9 per cent.
Sensation in abdomen in 4.6 per cent.
Sensation in throat in 6.9 per cent.
Sensation in left side in 2.3 per cent.
Sensation in both hands in 2.3 per cent.
Sensation in one hand in 2.3 per cent.
Violent pain in head in 2.3 per cent.
Pain in one foot in 2.3 per cent.
Sparkling sensation in eyes in 6.9 per cent.
Pumping sensation in head in 4.6 per cent.
Noises in ears in 4.6 per cent.
Diplopia in 2.3 per cent.
Contraction of one leg in 2.3 per cent.
Rotation of head in 2.3 per cent.
Distortion of face in 2.3 per cent.
Twitching of thumb in 2.3 per cent.
Spasm of eye-balls in 2.3 per cent.
Disagreeable smell in 2.3 per cent.
From these figures we find that in 34.4 per cent. of the cases of
epilepsia gravior there are no special symptoms announcing the seizure,
which takes place without warning of any kind; and it is especially in
such cases that patients in falling, seriously injure themselves. In
65.5 per cent. there are premonitory symptoms of some kind, which
indicate often many hours before the approach of an attack. Of these
last 47.4 per cent. are of a general character, and in no less than 72.8
per cent. is there a distinct special aura, which in 25.4 per cent.
alone precede the attack, the remainder being associated with the
general premonitory symptoms.
_Symptoms of the Attack._--In the cases of epilepsia gravior there were
complete loss of consciousness with convulsions, lasting from five to
ten minutes, and occurring at intervals, leaving no question as to the
true nature of the disease, and all doubtful examples have been excluded
from this collection. Attempts were made to form an analysis of the
different symptoms constituting the paroxysm, but with indifferent
success, and these are not here reproduced, because they are not
sufficiently accurate for scientific purposes. The patient himself can
give no account of what takes place. The friends around do not look upon
the phenomena of the attack with the critical and philosophic eye of the
physician; hence any information from them as to the part convulsed, the
colour of the skin, the duration of the seizure, and so on, is extremely
vague and untrustworthy. The number of cases personally observed
actually during attacks is too limited to warrant any generalizations.
There is, however, one important point which can be accurately
demonstrated--namely, whether or not the tongue is bitten, and in the
cases under observation
The tongue was bitten in 68.8 per cent.
The tongue was not bitten in 31.2 per cent.
_Frequency of Attacks._--Only a general average of the number of attacks
can be made; and in the present series the following gives an idea of
the frequency of seizures in different individuals.
Average of one or more attacks per day in 8.8 per cent.
Average of one or more attacks per week in 31.1 per cent.
Average of one or more attacks per month in 32.2 per cent.
Average of one or more attacks per year in 15.5 per cent.
At longer or more irregular intervals in 12.2 per cent.
This roughly indicates that, in the majority of cases, attacks of
epilepsia gravior occur one or more times weekly or monthly. Under the
last series, of attacks taking place at longer and more irregular
intervals than a year, are included those cases where a few only have
occurred during the lifetime of the patients.
_Regularity of Attacks._--Many epileptics are attacked at regular
intervals, sometimes on the same day or even hour; while others are
afflicted at any time, day or night. The following indicate the
proportion:--
Attacks occur at regular intervals in 21.1 per cent.
Attacks occur at irregular intervals in 78.8 per cent.
_Time of Attack._--The following particulars alone could be definitely
ascertained:--
Attacks only during sleep in 8.8 per cent.
Attacks only during day while awake in 8.8 per cent.
Attacks only during early morning in 15.5 per cent.
Attacks at no particular time in 55.4 per cent.
The chief feature of this observation is that in 15.5 per cent. of cases
of E. Gravior the attacks always took place immediately after the
patients had wakened in the morning, and this is probably due to the
sudden alteration of the cerebral circulation from the sleeping to the
wakeful state.
_Symptoms immediately after the Attack._--The moment the attack is over
sometimes the patient is in his usual condition, and feels no ill
effects from the paroxysm. More commonly, however, he suffers from
various symptoms, the chief of which, and their relative frequency, is
as follows:--
Return to usual condition in 12.2 per cent.
Drowsy in 66.6 per cent.
Confused in 14.4 per cent.
Stupid in 13.3 per cent.
Irritable in 14.4 per cent.
Excitable in 3.3 per cent.
Vertigo in 13.3 per cent.
Headache in 41.1 per cent.
The above conditions may last from an hour to several days.
_Present condition, or state between the Attacks._--It is impossible to
enter minutely into the actual physical and mental health of all the
epileptic cases under notice, but the following statement gives a
sketch of some of the more important conditions associated with the
disease, and the frequency with which they occur. In the
inter-paroxysmal state the condition of the patients were--
Healthy in every respect in 17.7 per cent.
With some abnormal peculiarity in 82.2 per cent.
General health good in 75.5 per cent.
General health impaired in 24.4 per cent.
Robust in 66.6 per cent.
Not robust in 33.3 per cent.
Intelligence intact in 74.4 per cent.
Intelligence impaired in 25.5 per cent.
Loss of memory in 58.8 per cent.
No loss of memory in 41.1 per cent.
Stupid in 16.6 per cent.
Dull in 31.1 per cent.
Irritable in 25.4 per cent.
Frequent headaches in 41.1 per cent.
Frequent vertigo in 22.2 per cent.
Nervous in 21.1 per cent.
Special diseases in 21.1 per cent.
Of the 21.1 per cent. under the heading of special diseases, there
were--
Hemiplegia in 6.6 per cent.
Paralysis of seventh nerve in 1.1 per cent.
Impediment of speech in 1.1 per cent.
Cicatrix over sciatic nerve in 1.1 per cent.
Idiot in 1.1 per cent.
Anaemia in 5.5 per cent.
Phthisis in 2.2 per cent.
Confirmed dyspepsia in 1.1 per cent.
From these details it is evident that epilepsy is not of necessity
associated with impairment of the physical or mental health. On the
contrary, we find that in 17.7 per cent. of the patients there was
apparently no flaw of any kind in their constitutions, which were
absolutely normal, with the exception of the periodic seizures. In no
less than 75.5 per cent. was the general health good, and in 66.6 per
cent. the patients were robust and vigorous. At the same time the
health was markedly impaired in 24.4 per cent., and the sufferers were
of delicate or weak habit in 33.3 per cent. The main fact, however, to
be observed is that, in the majority of cases of epilepsy, the general
health and vigour of the patient is not deteriorated. In the same way,
the intellectual capacities are not of necessity affected. In 74.4 per
cent. the intelligence is recorded as not seriously impaired; and in
41.1 per cent. the memory as good. On the other hand, the mental
faculties were markedly deficient in 25.5 per cent.; the patients were
dull and slow in 31.1 per cent.; and in more than half, or 58.8 per
cent., was there evidence of loss of memory. Another frequent symptom is
repeated and constant headache, which, in the present series of cases,
existed in 41.1 per cent.
2.--EPILEPSIA MITIOR.
This occurred altogether in 38 per cent. of the total number of cases.
In these it occurred--
By itself in 26.3 per cent.
Associated with E. Gravior in 73.6 per cent.
In all, the usual characteristics of the _petit mal_ presented
themselves; there being temporary loss of consciousness, sometimes with
slight spasms, but without true convulsion, biting of the tongue, &c.
_Frequency of Attacks._--The rough average frequency of attacks, as
estimated in the cases under consideration, was as follows:--
20 to 30 attacks per day in 3.7 per cent.
10 to 20 attacks per day in 7.4 per cent.
5 to 10 attacks per day in 14.8 per cent.
1 to 5 attacks per day in 40.7 per cent.
1 or more attacks per week in 22.2 per cent.
1 or more attacks per month in 7.4 per cent.
At rarer intervals in 3.7 per cent.
Thus when epilepsia mitior exists, in the majority of cases the attacks
are of daily occurrence.
_Loss of consciousness_, as ascertained in a series of cases, was
Complete in 48.3 per cent.
Partial in 51.6 per cent.
_Premonitory Symptoms._--These are not, as a rule, so well marked in
epilepsia mitior as in E. Gravior; but frequently the aura is quite as
distinctly appreciated. In the 28 per cent. of cases in which E. Mitior
is associated with E. Gravior, the aura was apparently the same in both.
Of the 10 per cent. cases of E. Mitior occurring by itself, the
following is the record:--
No aura in 20 per cent.
Sensation in epigastrium in 20 per cent.
Loss of speech in 10 per cent.
Violent pain in head in 10 per cent.
Tingling of extremities in 10 per cent.
Choking sensation in 10 per cent.
Hallucination in 10 per cent.
Vertigo in 10 per cent.
The number of cases in E. Mitior is too limited to warrant further
generalization.
FOOTNOTES:
[A] Reprinted from the "British Medical Journal" of March 15 & 22, 1879.
II.
AN INQUIRY
INTO THE
ACTION OF THE BROMIDES ON
EPILEPTIC ATTACKS.[B]
Bromide of potassium is generally recognised as the most effective
anti-epileptic remedy we at present possess. There exists, however,
great difference of opinion as to its method of administration and to
the amount of benefit which we may expect from its use. Some physicians
who employ the drug after one method come to totally different
conclusions as to its efficacy from those who use another. Many believe
the remedy to be only useful in certain forms of the disease, and to be
very uncertain and imperfect in its action. Others, again, maintain that
it is positively injurious to the general health of the patient. These
and other unsettled points the following inquiry attempts to make clear.
Epilepsy, like all other chronic diseases, presents great difficulties
in scientifically estimating the exact value of any particular remedy;
and unless the investigation of the subject is approached with the
strictest impartiality, and observations made with rigid accuracy, we
are liable to fall into the most misleading fallacies. I believe that
these are to be avoided, and facts arrived at, however laborious it may
be to the experimenter and wearisome to the student, only by the careful
observation and elaborate record of an extensive series of cases. If, in
epilepsy, the disease, from its prolonged duration, its doubtful
causation and pathology, its serious complications and the many other
mysterious circumstances connected with it, offers almost unsurmountable
difficulties to any definite and uniform method of treatment and the
systematic estimation of the same, its symptoms furnish us with
tolerably accurate data upon which to base our observations. The
attacks, although only symptoms, may be practically considered as
representing the disease, as in the large majority of cases, in
proportion as these are frequent and severe, so much the more serious is
the affection. The influence of the bromides on these paroxysms is taken
in the following inquiry to represent the action of these drugs on the
epileptic state.
Before proceeding to detail the facts arrived at, it is necessary
briefly to state the method of procedure adopted in treatment. Each case
in succession, and without selection, which was pronounced to be
epilepsy (all doubtful cases being eliminated), was considered as a
subject suitable for experiment. The general circumstances of the
individual were studied; his diet, hygienic surroundings, habits, and so
on, if faulty, were, when practicable, improved. The bromides were then
ordered, and taken without intermission for periods which will
subsequently be detailed. The minimum quantity for an adult, to begin
with, was thirty grains three times a day, the first dose half an hour
before rising in the morning, the second in the middle of the day on an
empty stomach, and the third at bedtime. This was continued for a
fortnight, and if with success, was persevered with, according to
circumstances, for a period varying from two to six months. If, on the
other hand, the attacks were not materially diminished in frequency, the
dose was immediately increased by ten grains at a time till the
paroxysms were arrested. In this way as much as from sixty to eighty
grains have been administered three times daily, and, with one or two
isolated exceptions to be afterwards pointed out, I have met with no
case of epilepsy which altogether resisted the influence of these large
doses; and, moreover, I have never seen any really serious symptoms of
poisoning or injury to the general health ensue in consequence.
Sometimes these quantities of the drugs have been taken for many months
with advantage; but as a rule it is preferable, when possible, after a
few weeks gradually to diminish the dose and endeavour to secure that
amount which, while it does not injuriously affect the general condition
of the patient, serves to keep the epileptic attacks in subjection. The
form of prescription to begin with in an adult has been as follows:--
R. Pot. bromid., gr. xv.
Ammon. bromid., gr. xv.
Sp. ammon. aromat., m. xx.
Infus. quassia, ad [Symbol: Apothecaries' ounce]j
M. Ft. haust. ter die, sumendus.
According to the age of the patient so must the dose be regulated; at
the same time, children bear the drug very well. The average quantity to
begin with for a child of ten or twelve years has been twenty grains
thrice daily.
In this manner I have personally treated about two hundred cases, and in
all of these most careful records have been kept, not only of their past
history, present condition, etc., but of their progress during
observation. All these, however, are not available for the present
inquiry. It is necessary in order to judge of the true effect of a drug
in epilepsy that the patient should be under its influence continuously
for a certain period of time. Now, a large number of patients,
especially amongst the working classes, cannot or will not be induced to
persevere in the prolonged treatment necessary in so chronic a disease.
They either weary of the monotony of drinking physic, especially if, as
is often the case, they are relieved for the time, or other
circumstances prevent their carrying out the regimen to its full extent.
The minimum time I have fixed as a test for judging the influence of the
bromides on epileptic seizures is six months, and the maximum in my own
experience extends to four years.[C] All other cases have been
eliminated. I have arranged this experience in the form of tables for
reference, in which will be seen at a glance--_1st_, the average number
of attacks per month in each case prior to treatment; _2nd_, the average
number of attacks per month after treatment; and _3rd_, in the event of
these being fewer than one seizure per month, the total number during
the last six months of treatment.
TABLE I.--_Sixty Cases of Epilepsy, showing Results of Treatment by the
Bromides during a Period of from 6 Months to 1 Year._
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1 900 60 --
2 600 5 --
3 600 90 --
4 450 12 --
5 300 2 --
6 240 90 --
7 180 60 --
8 150 5 --
9 150 8 --
10 150 7 --
11 120 3 --
12 120 120 --
13 90 3 --
14 90 9 --
15 70 20 --
16 60 4 --
17 60 6 --
18 60 90 --
19 30 7 --
20 30 1 --
21 30 2 --
22 30 10 --
23 16 8 --
24 16 2 --
25 12 4 --
26 12 12 --
27 12 3 --
28 8 0 0
29 8 2 --
30 8 1 --
31 8 1 --
32 8 -- 4
33 8 1 --
34 8 4 --
35 6 0 0
36 5 -- 5
37 5 0 0
38 4 2 --
39 4 1 --
40 4 1 --
41 4 1 --
42 4 -- 2
43 4 -- 3
44 2 -- 3
45 2 -- 2
46 2 -- 1
47 2 -- 1
48 2 -- 4
49 2 -- 1
50 2 -- 2
51 1 0 0
52 1 -- 2
53 1 0 0
54 1 1 --
55 1 0 0
56 1 0 0
57 1 -- 1
58 1 -- 1
59 1 -- 1
60 1 150 --
TABLE II.--_Thirty-two Cases of Epilepsy, showing Results of Treatment
by the Bromides during a period of from 1 to 2 Years._
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1 900 60 --
2 600 120 --
3 300 30 --
4 180 60 --
5 150 -- 2
6 150 1 --
7 90 9 --
8 90 15 --
9 60 2 --
10 6 -- 4
11 30 -- 1
12 30 4 --
13 30 2 --
14 30 3 --
15 16 -- 8
16 12 3 --
17 8 0 0
18 8 -- 3
19 8 -- 4
20 8 -- 1
21 8 -- 10
22 6 -- 1
23 4 -- 4
24 4 -- 4
25 4 2 --
26 2 -- 1
27 2 -- 2
28 2 -- 2
29 1 0 0
30 1 0 0
31 1 -- 3
32 1 -- 3
TABLE III.--_Seventeen Cases of Epilepsy, showing Results of Treatment
by the Bromides during a Period of from Two to Three Years._
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1 600 60 --
2 300 15 --
3 60 -- 8
4 30 -- 4
5 30 -- 8
6 30 -- 2
7 16 2 --
8 12 -- 8
9 8 -- 2
10 8 -- 1
11 8 -- 3
12 4 -- 1
13 4 1 --
14 4 6 --
15 1 0 0
16 1 0 0
17 1 -- 3
TABLE IV.--_Eight Cases of Epilepsy, showing the Results of Treatment by
the Bromides during a period of from Three to Four Years._
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1 300 3 --
2 60 1 --
3 60 4 --
4 30 1 --
5 16 -- 10
6 12 -- 3
7 8 0 0
8 1 0 0
These four tables consist of all the characteristic cases of epilepsy
which came under notice, without selection of any kind, all being
included, no matter what their form or severity, their age, complication
with organic disease, etc. In analyzing this miscellaneous series, the
chief fact to be noticed, whether the period of treatment has been
limited to six months or extended to four years, is the remarkable
effect of treatment upon the number of the epileptic seizures. Of the
total 117 cases, in 14, or about 12.1 per cent., the attacks were
entirely arrested during the whole period of treatment. In 97, or about
83.3 per cent., the monthly number of seizures was diminished. In 3, or
about 2.3 per cent., there was no change either for better or worse; and
in 3, or about 2.3 per cent., the attacks were more frequent after
treatment.
With regard to the fourteen cases which were free from attacks during
treatment, it cannot, of course, be maintained that all of these were
cured in the strict sense of the term. It is probable that if any of
them discontinued the medicine the seizures would return. Still, the
results are such as to encourage a hope that if the bromides are
persevered with, and the attacks arrested for a sufficiently long
period, a permanent result might be anticipated. Even should no such
ultimate object be realized, it is obvious that an agent which can,
during its administration, completely cut short the distressing
epileptic paroxysms, without injuriously affecting the mental or bodily
health, is of immense importance. Take, for example, cases 7 and 8 of
Table IV., where, prior to treatment, in the one case eight fits a
month, and in the other one, were completely arrested during a period of
nearly four years. The experience of physicians agrees in considering
that the danger of epilepsy, both to mind and body, is in great part
directly proportionate to the severity of its symptoms. If these latter
can be completely arrested, even should we be compelled to continue the
treatment, if this is without injury to the patient, it is as close an
approach to cure as we can ever expect to arrive at by therapeutic
means. The permanent nature of the improvement, and the possibility of
subsequent discontinuance of the bromides without return of the disease,
is a question I shall not enter into, as my own personal experience is
not yet sufficiently extended to be able to form a practical opinion. A
satisfactory solution of this problem could only be made after a
life-long private practice, or by the accumulated experience of many
observers. With hospital patients such is almost impossible, as they are
lost sight of, especially if they recover.
Of the total 117 cases which compose the tables, we find that in no less
than 97 were the attacks beneficially influenced by the bromides. In the
different cases this improvement varies in degree, but in most of them
it is very considerable--for example, Nos. 2, 5, 8, 11, 20, in Table I;
Nos. 5, 6, 11, 15, in Table II; Nos. 3, 4, 5, 6, in Table III; and all
the cases in Table IV. In these and others the attacks, if not actually
arrested, were so enormously curtailed, both in number and severity, in
comparison to what existed before treatment, as to constitute a most
important change in the condition of the patient. In those cases in
which improvement was not so well marked, in many it was most decided,
and in frequent instances caused life, which had become a burden to the
patient and his friends, to be bearable.
Of the total number of cases, in 3 the administration of the bromides
had no effect whatever in diminishing the attacks, and in 3 others the
number of seizures was greater after treatment than before. Whether in
these last this circumstance was the result of the drug, or due to some
co-incident augmentation of the disease itself, I cannot decide, but am
inclined to believe in the latter as the explanation.
After a consideration of these facts it is difficult to understand why
most physicians look upon epilepsy as an _opprobrium medicinae_, and of
all diseases as one of the least amenable to treatment, and the despair
of the therapeutist. For example, Nothnagel, one of the most recent and
representative authorities on the subject, in speaking of the treatment
of epilepsy, says, "Many remedies and methods of treatment have isolated
successes to show, but nothing is to be depended on; nothing can, on a
careful discrimination of cases, afford a sure prospect of recovery, or
even improvement." Such a statement indicates either an imperfect method
of treatment, or that in Germany epilepsy is more intractable than in
this country, as a "careful discrimination" of the above cases affords a
"sure prospect of improvement" and a reasonable one of recovery. That a
critical spirit and healthy scepticism should exist regarding the vague
and imperfect accounts of the efficacy of various drugs in disease is, I
believe, necessary to arrive at the truth; at the same time, we must not
refuse to credit evidence sufficiently based on observation and
experiment. The above collection of cases are facts, carefully and
laboriously recorded, and not originally intended for the purpose which
they at present fulfil. Having been brought up in the belief that
epilepsy was one of the most intractable of diseases, no one is more
surprised than myself at the readiness with which it responds to
treatment. So far, then, from this affection being the despair of the
profession, I believe that of all chronic nervous diseases it is the one
most amenable to treatment by drugs, resulting, if not in complete cure,
in great amelioration of the symptoms which practically constitute the
disease.
An important consideration next arises. Assuming that practically the
treatment in all cases is alike, are there any special circumstances
which explain why some patients should have no attacks while under the
influence of the drugs, while others are only relieved; why some--though
the number is very small--should receive no benefit, and others have a
larger number of attacks after treatment? On a careful examination of
all the clinical facts of each case, no explanation can be found, the
same form of attack, the same complications and circumstances, occupying
each group. For example, one of those who had no attacks during
treatment was a woman who had been afflicted with epilepsy for eighteen
years, of a severe form, with general convulsions, biting tongue, etc.
Another was a very delicate, nervous woman, who suffered, in addition to
the seizures, from pulmonary and laryngeal phthisis, who came of a
family impregnated with epilepsy, and whose intellect was greatly
impaired. By far the largest class are those benefited by treatment, and
these comprehend every species of case, chronic and recent, complicated,
inherited, in the old and young, and so on; yet the most careful
analysis fails to discover why some should be more amenable to treatment
than others, or give any indication which might be useful in prognosis.
Neither does a study of the few cases which the bromides did not affect,
or those which increased in severity under their influence, throw any
light upon the subject, as some of these latter gave no indications
beforehand of their unfortunate termination, and in none of them was
there any serious complication or special departure from good mental or
bodily health.
Another point must be noted, although there is no statistical method of
demonstrating the fact, namely, that in those cases in which the attacks
were not completely arrested, but only diminished in number, those
seizures which remained were frequently greatly modified in character
while the patient was under the influence of the bromides. These were
less severe, and characterized by the patients as "slight," while
formerly they were "strong." This by itself often proves of great
service, as, instead of a severe convulsive fit, in which the patient
severely injures himself, bites his tongue, etc., he has what he calls a
"sensation," in other words, an abortive attack.
Having considered the general effects of the bromides on a series of
unselected cases, we now proceed to investigate whether any particular
form of the disease, or any special circumstances connected with the
patient or his surroundings, have any influence in modifying the results
of treatment. The following table shows epilepsy divided into its two
chief forms, namely, E. Gravior and E. Mitior. By the former is
understood the ordinary severe attack, with loss of consciousness and
convulsions; the latter is the slighter and very temporary seizure, of
loss of consciousness, but without convulsions.
TABLE V.--_Showing Results of Treatment by the Bromides in_--1.
_Epilepsia Gravior_; _and_ 2. _Epilepsia Mitior._
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1. _Epilepsia Gravior_.
1 600 5 --
2 450 12 --
3 249 90 --
4 180 60 --
5 120 3 --
6 60 1 --
7 60 6 --
8 30 -- 8
9 30 4 --
10 30 12 --
11 23 1 --
12 16 2 --
13 12 -- 4
14 12 3 --
15 12 10 --
16 8 0 0
17 8 -- 4
18 8 1 --
19 8 4 --
20 8 2 --
21 6 -- 1
22 5 -- 5
23 5 0 0
24 4 -- 2
25 4 1 --
26 4 2 --
27 2 -- 1
28 2 -- 1
29 2 -- 1
30 2 -- 1
31 2 -- 2
32 2 -- 2
33 1 0 0
34 1 0 0
35 1 0 0
36 1 0 0
37 1 0 0
38 1 0 0
39 1 -- 1
40 1 -- 1
41 1 -- 1
42 1 -- 1
43 1 -- 2
44 1 -- 4
45 1 -- 2
46 1 1 --
47 1 150 --
2. _Epilepsia Mitior_.
1 900 60 --
2 600 60 --
3 300 3 --
4 150 1 --
5 150 7 --
6 120 120 --
7 90 9 --
8 90 3 --
9 60 15 --
10 60 90 --
11 13 -- 2
12 16 -- 4
13 16 -- 8
14 8 -- 3
15 8 -- 3
16 4 -- 1
17 4 6 --
18 1 -- 4
Of 47 cases of E. Major, we find that in 8 there were no attacks during
the whole period of treatment, in 1 there was no improvement, in 1 the
attacks were augmented after treatment, and in 37 there was marked and
varying diminution of the seizures. Of 18 cases of E. Mitior there was
no case where the attacks were wholly suspended, in 1 there was no
improvement, in 2 the attacks were increased, and in 15 they were
diminished in number by treatment. This is scarcely a fair comparison
between the two forms, as the numbers are so unequal; but cases of
uncomplicated E. Mitior are not common, being generally associated with
the graver form, which combined cases are not inserted in this table. It
is generally asserted in books that the non-convulsive form is much more
intractable than the other, but the above table proves the contrary, as,
for example, in Nos. 3, 4, 11, 12. It is true that the results do not
appear so complete or striking in E. Mitior as in E. Gravior, but then
it must be remembered that the number of cases is more limited, and the
number of attacks originally much greater. In short, the table shows
that if treatment does not completely avert the attacks of E. Mitior, it
greatly diminishes their frequency.
TABLE VI.--_Showing Effects of Treatment by the Bromides in Epilepsy. 1.
Diurnal Form; 2. Nocturnal Form_.
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1. _Diurnal Form_.
1 300 3 --
2 90 9 --
3 60 6 --
4 30 -- 8
5 24 1 --
6 16 -- 8
7 12 -- 4
8 8 -- 3
9 8 -- 4
10 4 1 --
11 2 -- 1
12 1 0 0
13 1 0 0
14 1 0 0
15 1 -- 1
2. _Nocturnal Form_.
1 60 1 --
2 16 -- 4
3 8 2 --
4 2 -- 1
5 4 -- 2
6 1 -- --
7 1 150 --
Another variety of epilepsy is that which is characterized by the time
at which the attacks occur. In the large majority of cases these take
place both while the patient is awake and when he is asleep. I have,
unfortunately, no observations to offer as to the effects of treatment
on the diurnal or nocturnal attacks in patients suffering from both. The
preceding table shows the result of treatment in 15 cases in which the
attacks occurred only while the patient was awake, and in 7 cases where
they took place only while he was asleep.
Of 15 cases of the purely diurnal form, we find that in 3 there was a
total cessation of attacks during treatment, and in all the others there
was diminution in their number. Of the 7 nocturnal cases, in none were
the seizures entirely arrested, in 1 the attacks increased in number
after treatment, and the remainder were relieved to a greater or less
extent. Here, again, our numbers are small, and therefore difficult to
found any definite principle upon; still there is enough to show that,
contrary to the opinion expressed by most authorities, the nocturnal
form of epilepsy appears to be as amenable to relief as the diurnal
variety.
The next point for consideration is the question whether the fact of the
epilepsy being hereditary or not makes any difference in the results of
treatment by the bromides. In the following table all the cases with a
perfectly sound family history are placed in the first part, and the
second includes those in which either epilepsy or insanity could be
proved to exist in any near relation.
Thus in 39 cases with a perfectly sound family history, in 3 the attacks
were totally arrested during treatment, in 2 there was no improvement,
in 2 there was increase of seizures after treatment, and in the
remainder there was diminution of the fits. In 18 cases, where at least
one near relation suffered from either epilepsy or insanity, in 3 the
attacks were arrested, in 1 they were increased, and in the remainder
diminished. In short, from a review of the details of the table, it does
not appear that the fact of the disease being inherited, or of its
existing in other members of the family, makes any difference to the
benefit we may expect to derive from treatment.
TABLE VII.--_Showing Effects of Treatment by the Bromides in Epilepsy._
1. _Non-Hereditary Cases_, 2. _Hereditary Cases_.
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1. _Non-Hereditary Cases._
1 600 5 --
2 600 60 --
3 450 12 --
4 240 90 --
5 300 3 --
6 150 7 --
7 120 3 --
8 120 120 --
9 150 1 --
10 70 20 --
11 60 6 --
12 60 90 --
13 60 1 --
14 30 12 --
15 90 3 --
16 30 -- 2
17 16 -- 4
18 16 2 --
19 8 0 0
20 8 2 --
21 8 -- 3
22 8 4 --
23 6 -- 1
24 5 0 0
25 5 -- 5
26 4 2 --
27 4 1 --
28 2 -- 2
29 2 -- 1
30 2 1 --
31 2 -- 2
32 1 0 0
33 1 -- 2
34 1 -- 4
35 1 1 --
36 1 -- 1
37 1 -- 1
38 1 -- 1
39 1 150 --
2. _Hereditary Cases._
1 900 60 --
2 180 60 --
3 90 9 --
4 24 1 --
5 16 -- 8
6 12 -- 4
7 12 3 --
8 8 1 --
9 8 -- 3
10 8 -- 4
11 4 -- 2
12 4 6 --
13 2 -- 1
14 2 -- 1
15 1 0 0
16 1 0 0
17 1 0 0
18 4 -- 1
The next table attempts to show whether or not the age of the patient
when he came under observation has any effect in modifying the action of
the bromides, or whether it assists us prognosing the probable result.
A survey of this table shows in general terms that the age of the
patient is neither an assistance nor impediment to the successful action
of the bromides in the treatment of epilepsy. Whatever the age may be,
whether in a young child or in an old person, the average of beneficial
effects appears to be the same. At first sight it would seem as if
treatment would be more successful in the young; but it is not so, as
the two cases in the table over fifty years of age received as much
average benefit as any of the others.
TABLE VIII.--_Showing Effects of Treatment by the Bromides in Epilepsy
at Different Ages_. 1. _Under 15 Years_; 2. _Between 15 and 30 Years_;
3. _Between 30 and 50 Years_; 4. _Over 50 Years_.
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1. _Under 15 Years._
1 900 60 --
2 600 5 --
3 600 60 --
4 450 12 --
5 240 90 --
6 180 60 --
7 150 7 --
8 30 4 --
9 8 0 0
10 8 -- 3
11 4 6 --
12 4 2 --
13 2 -- 1
14 1 150 --
2. _Between 15 and 30 Years._
1 300 3 --
2 150 7 --
3 120 3 --
4 120 120 --
5 90 3 --
6 60 1 --
7 60 6 --
8 60 90 --
9 16 -- 4
10 16 -- 8
11 16 2 --
12 12 -- 4
13 8 1 4
14 8 2 --
15 8 4 --
16 70 20 --
17 5 0 0
18 4 -- 2
19 4 1 --
20 4 1 --
21 2 -- 2
22 2 -- 1
23 2 -- 1
24 2 -- 2
25 1 0 0
26 1 0 0
27 1 0 0
28 1 -- 1
29 1 -- 2
30 1 -- 4
31 1 1 --
3. _Between 30 and 50 Years._
1 30 -- 2
2 30 -- 12
3 12 3 --
4 8 1 --
5 8 -- 3
6 5 -- 5
7 2 -- 2
8 1 0 0
9 1 -- 1
10 1 -- 1
4. _Over 50 Years._
1 30 -- 8
2 24 1 --
Does the fact of the disease being recent or chronic affect the
prognosis of treatment? This will be seen by the following table, in
which the length of time that the disease has existed is divided into
four periods, namely--1, those cases in which the attacks first began
less than a year before treatment was commenced; 2, those in which they
had begun from one to five years before; 3, those in which they began
from five to ten years before; and, 4, those in which the disease had
existed for over ten years.
TABLE IX.--_Showing Effects of Treatment by the Bromides in Epilepsy in
Recent and Chronic Cases. 1. Under 1 Year; 2. From 1 to 5 Years; 3. From
5 to 10 Years; 4. Over 10 Years._
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1. _Under 1 Year._
1 600 60 --
2 60 6 --
3 8 -- 3
4 5 0 0
5 4 -- 2
6 4 2 --
7 2 -- 1
8 2 -- 1
9 2 -- 2
2. _From 1 to 5 Years._
1 600 5 --
2 240 90 --
3 180 60 --
4 90 3 --
5 30 -- 2
6 30 -- 8
7 30 12 --
8 16 -- 8
9 12 3 --
10 8 0 0
11 150 7 --
12 8 2 --
13 6 1 --
14 4 -- 1
15 2 -- 1
16 2 -- 2
17 1 0 0
18 1 0 0
19 1 -- 1
20 1 1 --
21 1 150 --
3. _From 5 to 10 Years._
1 450 12 --
2 300 3 --
3 900 60 --
4 90 9 --
5 60 1 --
6 30 4 --
7 16 2 --
8 8 -- 4
9 8 -- 3
10 8 1 --
11 4 1 --
12 3 1 --
13 1 -- 1
14 1 -- 1
15 1 -- 2
4. _Over 10 Years._
1 150 1 --
2 120 3 --
3 120 120 --
4 70 20 --
5 60 90 --
6 16 -- 4
7 12 -- 4
8 8 4 --
9 5 -- 5
10 1 0 0
11 1 0 0
12 1 -- 4
In this table we observe very singular results in the treatment of this
remarkable disease. In most ailments, the longer they have existed and
the more chronic they are, the more difficult and imperfect is the
prospect of recovery. This does not appear to hold good in the case of
epilepsy. For when we analyze the above table we find that the results,
on an average, are as satisfactory in those cases in which the disease
has existed over ten years as in those which began less than one year
before the patient came under observation. For example, we find in
section 4 of Table IX. 12 cases in which epilepsy had existed for over
ten years prior to treatment; of these, in 2 the attacks were completely
arrested, in 1 there was no improvement, in 1 the attacks were
increased, and in the remainder the seizures were as beneficially
modified as in the other sections. Thus it would seem that we are not to
be deterred from treating cases of epilepsy, however chronic they may
be, as the results appear to be as good in modifying the attacks in old,
as in recent cases.
TABLE X.--_Showing Effects of Treatment by the Bromides in Epilepsy--1.
In Healthy Persons; 2. In Diseased Persons._
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1. _Healthy Persons._
1 900 60 --
2 600 60 --
3 150 7 --
4 150 1 --
5 120 3 --
6 90 9 --
7 70 20 --
8 60 1 --
9 60 5 --
10 60 90 --
11 30 -- 2
12 30 -- 8
13 30 12 --
14 16 0 0
15 16 2 --
16 16 -- 4
17 12 3 --
18 8 2 --
19 8 0 0
20 8 -- 3
21 8 -- 4
22 8 4 --
23 4 2 --
24 4 1 --
25 4 2 --
26 2 -- 1
27 2 -- 2
28 2 -- 1
29 2 -- 1
30 2 -- 2
31 2 -- 1
32 1 0 0
33 1 -- 2
34 1 1 --
35 1 0 0
36 1 0 0
37 1 -- 1
38 1 -- 1
39 1 -- 1
40 1 1 4
41 1 150 --
2. _Diseased Persons._
1 450 12 --
2 300 3 --
3 240 90 --
4 180 60 --
5 90 3 --
6 60 6 --
7 24 1 --
8 12 -- 4
9 8 -- 3
10 8 1 --
11 6 -- 1
12 5 -- 5
13 4 -- 1
14 4 6 --
15 1 0 0
Another important question arises: Does the general health of the
patient in any way influence the effects of treatment? In the preceding
table those cases are collected in section 1 whose general health was to
all appearances robust and free from disease. In section 2. are those in
which organic disease could be demonstrated, or in which the condition
of the patient was evidently unfavourable.
Here, again, a consideration of the table demonstrates that the
condition of the general health has no influence on the successful
progress of treatment, as those cases under the head of diseased persons
made apparently as satisfactory progress as those in a perfectly robust
condition regarding their epileptic symptoms.
As a specimen, the following table shows the result in those cases
complicated with a permanent lesion of a motor part of the brain,
namely, hemiplegia, and of an intellectual portion, in the shape of
idiocy:--
TABLE XI.--_Showing effects of Treatment by the Bromides in Epilepsy
complicated with--1. Hemiplegia; 2. Idiocy_.
Average Average Number
No. number number attacks
of attacks attacks during
Case. per month per month last 6
_before_ _after_ months of
treatment. treatment. treatment.
1. _Hemiplegia._
1 450 12 --
2 240 90 --
3 30 4 --
4 24 1 --
5 8 -- 3
6 8 1 --
7 4 6 --
2. _Idiocy._
1 180 60 --
2 120 120 --
3 60 6 --
4 30 4 --
5 4 6 --
Here it may be observed that of 7 cases complicated with hemiplegia, in
1 the attacks were increased after treatment, but all the others were
relieved in average proportion. Of the 5 cases in idiots, in 1 there was
no improvement, in 1 the attacks were subsequently augmented, and in the
others there was improvement. The numbers are far too limited to found
any reliable dictum upon; at the same time, it must be admitted that
while epilepsy complicated with these grave lesions is perfectly
amenable to treatment, this table serves to show that the proportion of
non-success is comparatively large.
It has been stated before that no attempt would be made in this paper to
prove that epilepsy was curable by therapeutic means. Its aim has been
to show the effects of the bromides on the attacks or symptoms of that
disease. It is common to hear it remarked, as if this were of no
importance, "You only arrest the fits, but you do not know, and cannot
cure, the original lesion. You do not go to the fountain-head of the
disease, but simply relieve its results." In reply, I would ask, Of what
disease do we know the ultimate nature any better than that of epilepsy?
and if we did, how would that assist us in treating it? What drug in our
pharmacopoeia cures any single disease, or do other than, by attacking
and relieving symptoms, leave nature to remove the morbid lesion? Even
quinine, to which therapeutists triumphantly point, only arrests certain
paroxysms until time removes the poison from the blood, as it does in
most malarious affections. So far from being a small matter, I believe
there are few, if any, drugs at our disposal which can be demonstrated
to have a more beneficial action in the treatment of disease than that
of the bromides, in epilepsy. Besides, I decline to admit the statement
that complete recovery does not follow their administration. Various
authors have reported cases, and that these are rare is due to reasons
stated before, and chiefly on account of the long period of treatment
necessary to ensure success.
This inquiry may be summed up in the following general conclusions:--
1. In 12.1 per cent. of epileptics the attacks were completely arrested
during the whole period of treatment by the bromides.
2. In 83.3 per cent. the attacks were greatly diminished both in number
and severity.
3. In 2.3 per cent. the treatment had no apparent effect.
4. In 2.3 per cent. the number of attacks was augmented during the
period of treatment.
5. The form of the disease, whether it was inherited or not, whether
complicated or not, recent or chronic, in the young or in the old, in
healthy or diseased persons, appeared in no way to influence treatment,
the success being nearly in the _same ratio_ under all these
conditions.
FOOTNOTES:
[B] Reprinted from the "Edinburgh Medical Journal" for February and
March, 1881.
[C] For an extended experience, see the next paper.
III.
AN INQUIRY
INTO THE
EFFECTS OF THE PROLONGED
ADMINISTRATION OF THE BROMIDES
IN EPILEPSY.[D]
The present inquiry is the result of an experience of 300 cases of
epilepsy treated by myself with the bromides of potassium and ammonium.
In all of these the clinical facts, as well as the progress of the
malady, were carefully studied and recorded. The effects of the
administration of these remedies on epileptic seizures I have already
investigated and demonstrated in a somewhat elaborate series of
observations.[E] Further experience has confirmed the correctness of the
general propositions then arrived at, so that they need not again be
elaborated in detail.
At present it is proposed to direct attention to the effects of the
prolonged administration of large doses of the bromides, and to attempt
to ascertain if, while arresting or diminishing the frequency and
severity of the paroxysmal symptoms, they beneficially influence the
disease itself, or in any way injuriously modify the constitution of the
patient. On this subject much difference of opinion and misconception
prevail. It is well known that the injudicious use of the drugs leads to
certain physiological phenomena which are comprised under the term
"bromism." It is also generally believed that the physical and mental
depression resulting from their prolonged toxic effects constitutes a
condition worse than the malady for which they are exhibited. One of the
objects of this article is to question the accuracy of this assertion,
a true apprehension of which is the more important when we reflect how
universal is this method of treatment, and the deterrent effect it
exercises upon epileptic attacks. The task, like other therapeutic
inquiries--especially those connected with chronic disease--is a
difficult one, there being innumerable pitfalls of error between us and
a sound scientific conclusion. These, however, may, I believe, in great
measure be surmounted by the accumulation of facts laboriously and
accurately recorded, by the intelligent study of their details, and the
impartial and logical deductions which may be drawn from the data
supplied. The value of a therapeutic inquiry depends, not upon the
opinions and undigested experience of individuals, or by the narration
of isolated cases, but upon the indisputable proofs resulting from the
unbiassed analysis of a large series of accurately observed and
unselected examples. The solution of the problem, if complex in all
clinical affections, is especially so in epilepsy. Although the symptoms
of this disease have been recognised from the earliest ages, our
knowledge of its essential nature is as yet shrouded in mystery. The
etiology and pathology are practically undetermined. The phenomena are
not only due to a varied series of morbid conditions, but may assume a
multitude of forms and degrees of severity, which may be, on the one
hand, of the briefest duration, or, on the other, of a life-long
permanence. The symptoms may comprise not only a diversity of physical
ailments, but intellectual disturbances of the most terrible import. The
malady may attack not only many whose systems are predisposed to
disease, but those of the most robust constitution and with a healthy,
family history. The consequences of the disorder may be comparatively
innocuous, but in other circumstances may be attended with the most
disastrous effects on mind and body and even on life itself. In a
disease presenting such an intricate and uncertain course, it is
obviously a task of the utmost difficulty to scientifically estimate the
exact value of any therapeutic measures which may be adopted for its
relief. The effects on one symptom, and that the most prominent, can,
however, be accurately determined--namely, the paroxysmal seizures,
which are definite and computable; and this has already been
accomplished with tolerable precision.[F] On the influence of the
bromides on the disease itself, or on the epileptic state, we have less
accurate information. In attempting to throw some light on this subject,
two preliminary considerations must be recognised--1st, the
physiological actions of the drug on the healthy subject; and 2nd, the
inter-paroxysmal symptoms of the epileptic constitution.
1. Medicinal doses of the bromides produce in healthy persons a general
diminution of nervous energy. They act as a sedative, and thus dispose
to repose and sleep. If they are excessive in quantity and long
continued, especially in those susceptible to their action, a series of
toxic effects are produced. Various organs and functions of the body are
influenced, and the results of the poison may be briefly summed up as
follows:--The intellectual faculties are blunted, the memory is
impaired, the ideas confused, the patient is dull, stupid, and
apathetic, and has a constant tendency to somnolence. The speech is
impeded and slow, and the tongue is tremulous. The special senses are
weakened. The body, as a whole, is infirm, the limbs feeble, and the
gait staggering and incoordinated. The reflex excitability is lowered
and the sensibility diminished. The sexual powers are impaired or
abolished. These symptoms may be present in a variety of degrees, and in
advanced cases even imbecility or paralysis may ensue. The mucous
membranes become dry and insensitive, especially those of the fauces.
This is attended with various functional disorders, such as nausea,
flatulence, gastric catarrh, diarrhoea, &c. The skin is pale, and the
extremities are cold. The action of the heart is slow and weak. The
respiration is shallow, hurried, and imperfect. The integument is
frequently covered with an acne-like eruption. To these symptoms may be
added a general cachexia. All these abnormal conditions, as a rule,
disappear when the consumption of the poison is arrested.
2. Although some persons, suffering from epileptic seizures, are, in the
intervals, of sound mind and body, in many the inter-paroxysmal state is
characterized by certain symptoms peculiar to this condition, and
independent of any form of treatment. These vary from the slightest
departures from health to the most serious mental and physical disease.
The general health is frequently unsatisfactory; the functions of the
body being impaired in vigour, the digestion is weak, and the
circulation feeble. The entire nervous system is in an unstable
condition, the patient being at one time irritable and excitable, and at
another depressed and despondent. There is a very common condition of
so-called "nervousness" which is accompanied by headache, pains,
tremors, and a variety of other subjective phenomena. The mental powers
are enfeebled, the memory defective, and these intellectual alterations
may exist in any degree, even to permanent and intractable forms of
insanity. The physical conditions may also be changed, the nutrition of
the tissues is often imperfect, the skin is pale, the muscles flabby,
and the motor powers generally enfeebled, all of which may also present
different degrees of severity, so as to culminate in actual paralysis.
Admitting, then, that the prolonged and excessive administration of the
bromides causes a series of abnormal symptoms in the healthy individual,
affecting mainly the general nutrition, the mental faculties, and the
sensory and motor functions, and also that the epileptic state is itself
frequently accompanied by impairment of innervation of a somewhat
analogous nature, it follows that when the drug is given for the relief
of the disease, care must be taken not to confound the two series of
phenomena with one another. With this precaution in view, granting that
the therapeutic agent beneficially controls and suppresses the
convulsive seizures, we proceed to discuss whether in so doing it in any
way injuriously influences the constitution of the patient. To answer
this question has been found by no means easy. Comparatively few
physicians have opportunities of observing cases of epilepsy in
sufficient numbers to form substantial conclusions on the subject. Even
in favoured circumstances it is difficult, especially in hospital
practice, to ensure the regular attendance of the patient or to keep him
sufficiently long under observation. The study and the recording of the
facts, moreover, demand an expenditure of much time and labour. These,
added to the sources of fallacy already enumerated, render the inquiry
a complicated one; but it is believed that an approximation to the truth
may be arrived at by the following method of investigation.
A large number of cases of epilepsy form the basis of the statistics,
the great majority of whom are adults. No selection of any kind is made,
and all are admitted irrespective of the cause, nature, or severity of
the disease. The particulars of each having been noted, treatment by the
bromides was instituted, the minimum dose being one drachm and a half
daily,[G] which, if necessary, was further increased in quantity. The
progress of the patient was observed at frequent and regular intervals,
and if the attendance was irregular the case was excluded from the
present inquiry. The result of this proceeding is an aggregate of 141
cases, all of whom have been constantly under the influence of the drug
for periods varying from one to six years. These are arranged in groups
according to the length of time they were under treatment. The immense
mass of details thus collected, added to the varied circumstances
connected with individual cases, render it impossible, in constructing a
summary of the whole, to do more than select certain prominent features
of interest for examination and demonstration. These in tabular form are
as follows:--
TABLES SHOWING THE EFFECTS OF THE CONTINUOUS ADMINISTRATION OF THE
BROMIDES IN THE EPILEPTIC STATE, IN 141 CASES, THE CONDITION BEING
ASCERTAINED AT THE END OF EACH PERIOD.
I. _For one year (51 cases)._
Physical and mental powers unaffected 39, or 76.4 per cent.
Physical and mental powers impaired 6, or 11.7 per cent.
Physical powers alone impaired 3, or 5.9 per cent.
Mental powers alone impaired 2, or 3.9 per cent.
General symptoms of neurasthenia 13, or 25.4 per cent.
Bromide eruption 8, or 15.6 per cent.
II. _For two years (34 cases)._
Physical and mental powers unaffected 28, or 82.3 per cent.
Physical and mental powers impaired 2, or 5.8 per cent.
Physical powers alone impaired 1, or 2.9 per cent.
Mental powers alone impaired 2, or 5.8 per cent.
General symptoms of neurasthenia 5, or 14.7 per cent.
Bromide eruption 6, or 17.6 per cent.
III. _For three years (30 cases)._
Physical and mental powers unaffected 28, or 93.3 per cent.
Physical and mental powers impaired 1, or 3.3 per cent.
Physical powers alone impaired 1, or 3.3 per cent.
Mental powers alone impaired 0, or 0.0 per cent.
General symptoms of neurasthenia 3, or 10.0 per cent.
Bromide eruption 3, or 10.0 per cent.
IV. _For four years (16 cases)._
Physical and mental powers unaffected 12, or 75.0 per cent.
Physical and mental powers impaired 0, or 0.0 per cent.
Physical powers alone impaired 2, or 12.5 per cent.
Mental powers alone impaired 2, or 12.5 per cent.
General symptoms of neurasthenia 0, or 0.0 per cent.
Bromide eruption 2, or 12.5 per cent.
V. _For five years (6 cases)._
Physical and mental powers unaffected 6, or 100.0 per cent.
Physical and mental powers impaired 0, or 0.0 per cent.
Physical powers alone impaired 0, or 0.0 per cent.
Mental powers alone impaired 0, or 0.0 per cent.
General symptoms of neurasthenia 3, or 50.0 per cent.
Bromide eruption 0, or 0.0 per cent.
VI. _For six years (4 cases)._
Physical and mental powers unaffected 4, or 100.0 per cent.
Physical and mental powers impaired 0, or 0.0 per cent.
Physical powers alone impaired 0, or 0.0 per cent.
Mental powers alone impaired 0, or 0.0 per cent.
General symptoms of neurasthenia 2, or 50.0 per cent.
Bromide eruption 0, or 0.0 per cent.
In the construction of the details of the above tables, care has been
taken as far as possible to distinguish between the effects of the
remedy and the symptoms associated with the disease, although this has
not been always easy to accomplish. It has, however, been approximately
arrived at by a careful study of the patient's health before treatment,
as compared with his subsequent state, and those symptoms only were
considered toxic which were superadded to pre-existing abnormal
conditions. A general analysis of the facts thus collected shows that in
the majority of cases the physical and mental powers do not appear to be
injuriously affected by the prolonged use of the bromides. It is not
asserted that all the individuals placed under this section were
necessarily sound in mind and body. In many instances the functions of
these were impaired, but there was no evidence to indicate that this was
the result of the medicine taken; on the contrary, there was every
reason to believe that the symptoms thus displayed were a part of the
original disease, and had existed prior to treatment.
In a very small percentage of cases were both physical and mental powers
unfavourably modified as a direct consequence of the use of the
bromides, and even in these there is no absolute certainty that the
drugs were entirely responsible for the symptoms, seeing that these
might be attributed to the epileptic condition as well as to the toxic
effects of the remedy. They are considered under this category, as the
abnormal phenomena appeared to be augmented after treatment and improved
on its temporary cessation. They mainly consisted, on the one hand, of
loss of memory, dulness of apprehension, apathy, somnolence, depression
of spirits, and mental debility; and on the other, of bodily languor,
muscular fatigue, and general physical weakness. In no case did any of
these symptoms attain an excessive or prominent position. The same
conditions apply when the physical or mental powers were impaired
independently of one another.
Under the heading of general phenomena of neurasthenia is included a
series of indefinite subjective neurotic symptoms, without intellectual
or bodily deficiencies, in which the patient complained of headache,
neuralgic pains, tremors, of being easily startled and frightened, with
that general instability of the nervous system to which the term
neurasthenia has been given. This condition is extremely common in the
epileptic, and is frequently relieved by treatment. At other times it
remains persistent in spite of all medicaments, and the numbers in the
tables indicate those cases conspicuous by their continuance under the
use of the bromides. Those attacked by the follicular rash are seen at
first to be about 16 per cent., but gradually diminishing in number as
the treatment becomes chronic, and finally disappearing altogether.
In addition to the points referred to in the tables, other questions
have been investigated, although on a smaller scale. For example, in
persons who have been under the influence of the bromides for many
years, the skin and tendon reflex action remain intact, and I have never
seen a case in which the knee-jerk or plantar phenomena were absent. In
only one case was the general sensibility of the skin perceptibly
diminished. With regard to the effects on the sexual powers, I have not
sufficient data upon which to found positive rules. This statement,
however, may be made, that the prolonged use of even large doses of this
drug does not of necessity abolish or even sensibly impair this
function, although, no doubt, it usually does so. On examining the
respiration and pulse, I have never been able to detect any
characteristic abnormality.
I might record many cases in detail to prove the seemingly innocuous
nature of even large and long-continued doses of the bromides in
epilepsy. I shall, however, as an illustration, limit myself to a few
notes on the four cases which compose Table VI., all of whom were
continuously under the influence of the drugs for a period of not less
than six years.
CASE 1.--Louisa C----, aged twenty-nine, has suffered from epileptic
attacks for fourteen years. Prior to treatment she had three or four
every week, of a severe character, consisting of loss of consciousness,
general convulsions, biting of the tongue, &c. She has always been a
delicate person, with a tendency to great nervousness, but otherwise
intelligent, and in fair general health. She has taken one and a half
drachms of bromide of potassium daily regularly for the last six years,
and states that if she attempts to discontinue the medicine all her
symptoms are aggravated. At present the patient is a robust,
healthy-looking woman, of fair intelligence and good spirits. Her
memory is deficient. Her physical powers are vigorous, and she earns her
living as a bookbinder. She has an attack about once a month, and with
the exception of this and occasional headaches and nervousness, she
professes and seems to be in excellent general health. Sensibility, the
knee-jerk, and plantar phenomena are normal. The fauces are insensitive,
and their reflex is abolished. Pulse 60, normal. The circulation,
respiration, and other functions are healthy. No traces of bromism.
CASE 2.--Charles P----, aged thirty-five, has suffered from epileptic
attacks of a severe convulsive character for eighteen years, having had
one about once a month. Prior to treatment, although his memory was
defective, his intelligence and general health were good. For the last
six years he has regularly taken the bromides of potassium and ammonium
(one drachm and a half) daily. At present he still continues to have an
attack about once a month. His mental and physical conditions are the
same as before. He appears perfectly intelligent. His strength is
robust, so that he does his ordinary work as a pianoforte maker. Pulse
74, of good strength. All the reflexes are normal, except that of the
fauces, which is abolished. Sensibility of the skin to touch slightly
diminished. The sexual functions are normal. No symptoms of bromism.
CASE 3.--Matilda W----, aged thirty-one, has suffered from epilepsia
gravior and mitior for twenty-two years, having of the former about one
seizure in three months, and of the latter ten or twelve a day. She has
always been a delicate woman, suffering from headaches, general
irritability, and nervousness. She is, however, perfectly intelligent.
For six years past she has taken regularly the bromides of potassium and
ammonium, one drachm of each daily. She has not had an attack of
epilepsy major for a year, and of epilepsy mitior has now only about one
a week. Although anaemic, her general health is good, and she is able to
do a full day's work as a washer-woman. Intellectually she is quite
sound, but has a treacherous memory, and is very nervous. Sensibility,
reflex acts, &c., are as in the other cases.
CASE 4.--Lucy D----, aged twenty-two, has suffered from epilepsy major
for eight years. Formerly had about one attack a week. Has always been a
delicate girl, but her general health and mental condition have been
normal. For the last six years she has regularly taken one drachm and a
half of the bromides daily (potassium and ammonium in equal parts). She
has had only three attacks during the past year. Her general health is
excellent. She is robust and active, and takes her full share in
domestic work. She is well educated, intelligent, with good memory and
spirits, and has no tendency to depression or somnolence. The
sensibility, reflex acts, and other functions are as in the other cases.
In these four cases it has been ascertained that the patients were
constantly under the influence of large doses of the bromides for a
period of not less than six years, and practically without intermission.
During this period not only were the frequency and severity of the
convulsive attacks beneficially modified, but there was no evidence to
show that the physical or mental condition had been in any way impaired.
It is further to be observed that these as well as many others of those
constituting the later tables, are examples of unusually long-standing
and severe forms of epilepsy, as evidenced by the fact of their chronic
and intractable nature even under treatment. Notwithstanding the
incompleteness of their recovery, these individuals have voluntarily,
and often at great inconvenience and expense, persevered in the use of
the remedy, which is a fair indication they derived some substantial
benefit from it. The examples before us, one and all, declared they have
found by experience that when they have attempted, even for brief
periods, to discontinue the medicine their symptoms have all become
aggravated. As a result the attacks increase in severity and number, the
headaches return, the nervousness augments, and they are unable to
perform either mental or bodily exertion. These sufferings, it is
maintained, are greatly modified by the bromides, as under their
influence epileptics may perform their daily work, when without them
they are comparatively useless. It would be easy to multiply individual
cases supporting the same general principles. One more instance only
need be particularized--namely, that of a man aged thirty, who has
suffered from epilepsy from infancy, and who for the last five years
has taken _four and a half drachms_ of the bromides daily--_i.e._,
during that time he has consumed upwards of _eighty pounds_ of the drug.
Although a delicate person and intellectually weak, his friends state
that during those years he has been more healthy and robust in mind and
body than at any other period of his life. And these statements were
confirmed by other testimony.
While attempting to estimate the therapeutic value of the bromides from
a statistical aspect, one likely source of fallacy must not be
overlooked. Most patients, and especially those attending hospitals, are
difficult to keep under observation for long periods, more particularly
if the progress of the case is unsatisfactory. In this way we may lose
sight of those who do not benefit by treatment or who are injured by it.
Although it is difficult to estimate these with accuracy, a certain
rebatement must always be made on this count in computing results. At
the same time we have in the present inquiry positive evidence, in a
considerable number of cases, of the innocuous and beneficial nature of
the drug, against the negative possibility only of its disadvantages. Of
the 141 cases under notice, I only know of three who have died, and all
of then of phthisis pulmonalis. The relations existing between the
mortality and cause of death on the one hand, and the disease and
treatment on the other, the paucity of the data do not permit us to
determine.
A further study of the tables would also seem to show that while the
beneficial action of the bromides remains permanent, the deleterious
effects diminish the longer the drug has been taken. This is doubtless
due, as in the case of most poisons, to the system becoming habituated
to its use. It has often been observed that the most marked effects of
bromism have appeared at the beginning of treatment, and that the
eruption, the physical and mental depression, &c., subsequently
disappeared, although the medicine was persevered in. Those who have
been under its influence for some years rarely present any symptoms
directly attributable to the toxic effects of the bromides; and if
abnormal conditions do exist, these are the sequelae of the malady, and
not the results of treatment, as shown by the fact that when the last is
suspended, the original sufferings are augmented.
It may be suggested that a prolonged use of the bromides becomes, as in
the case of opium, a habit. There is, however, a marked distinction
between the two. Opium-smoking is a vice not only deleterious in itself,
but one indulged in merely to satisfy a morbid craving. The bromides, on
the other hand, are less hurtful in their effects, and are taken to
avert the symptoms of a distressing and terrible malady. Assuming, then,
that their consumption becomes a necessity, if it can be shown that the
results are not serious, while the evils they avert are important, the
habit acquired may be looked upon as a justifiable one.
A general review of all these circumstances seems to render it probable
that the epileptic constitution is more tolerant of the toxic effects of
the bromides than the healthy system. The most severe effects of bromism
occur in those who are not the victims of this malady, in whom, as seen
by the foregoing facts, they are not common. Theoretically this may be
plausibly explained by the reasonable assumption that, as in epilepsy
the entire nervous apparatus is in a state of reflex hyper-excitability,
the sedative and poisonous effects of the bromides do not produce the
depressing or toxic actions they would do in a more stable organization.
Whatever the reason may be, the fact is that the symptoms of bromism are
not so severe in the epileptic as they are in otherwise healthy
subjects.
Finally, the important question arises, Does a prolonged use of the
bromides tend towards the eradication of the disease itself and the
ultimate cure of the epileptic state? On this point I have no personal
statistical evidence to offer, nor am I aware of the existence of any
sufficiently scientific series of data to settle the question. Without
there being actual demonstration of the fact, there is every reason to
believe that such a supposition is possible. Clinical observation has
determined that the larger the number of convulsive seizures the greater
is the tendency to the production of others, and the more readily are
they caused. Such is the abnormal reflex hyper-excitability of the
nervous system of the epileptic that the irritative effects of one
attack seem directly to pre-dispose to the occurrence of a second; so
that the larger the number of explosions of nerve instability which
actually take place, the more there are likely to follow. Could such
seizures be kept in check, this cause of the production of convulsions
at least would be diminished, the liability for them to break out as a
result of trifling external stimuli would be lessened, and the
long-continued absence of this source of irritation might by the repose
and favourable circumstances thus obtained, encourage a healthy
transformation of tissue. Now, it has already been pointed out that in
12.1 per cent. of epileptics the attacks were completely arrested during
the entire time the drugs were being administered, and that in a much
larger percentage they were greatly modified in number and severity. It
has been further shown that the remedies themselves, even when in use
for long periods, are in themselves practically innocuous, while at the
same time they continue to maintain their beneficial effects on the
attacks. It therefore follows that a sufficiently prolonged treatment
might in a certain number of cases be succeeded by permanent curative
results. The chief impediment to arriving at trustworthy conclusions on
this subject has been the length of time necessary to judge of lasting
benefits, and the difficulty of keeping patients sufficiently long under
observation. Another has been the objection raised to the method of
treatment on the grounds of a visionary suspicion that the toxic effects
of the drug were of a dangerous nature, and their results more
distressing than the diseases for which they were given. So far as my
experience has extended, I believe this fear has not been warranted by
facts.
FOOTNOTES:
[D] Reprinted from the "Lancet" of May 17th and 24th, 1884.
[E] See Article II.
[F] Vide preceding paper.
[G] The usual prescription contained the bromides of potassium and
ammonium, fifteen grains of each for a dose.
_June, 1884._
CATALOGUE OF WORKS
PUBLISHED BY
H. K. LEWIS
136 GOWER STREET, LONDON, W.C.
============
G. GRANVILLE BANTOCK, M.D., F.R.C.S. EDIN.
_Surgeon to the Samaritan Free Hospital for Women and Children._
I.
ON THE USE AND ABUSE OF PESSARIES. With Illustrations, Second Edition,
8vo. [_In the press._
II.
A PLEA FOR EARLY OVARIOTOMY. Demy 8vo, 2s.
============
FANCOURT BARNES, M.D., M.R.C.P.
_Physician to the Chelsea Hospital for Women; Obstetric Physician to the
Great Northern Hospital, &c._
A GERMAN-ENGLISH DICTIONARY OF WORDS AND TERMS USED IN MEDICINE AND ITS
COGNATE SCIENCES. Square 12mo, Roxburgh binding, 9s.
============
ROBERTS BARTHOLOW, M.A., M.D., LL.D.
_Professor of Materia Medica and Therapeutics, in the Jefferson Medical
College of Philadelphia, etc., etc._
I.
A TREATISE ON THE PRACTICE OF MEDICINE, FOR THE USE OF STUDENTS AND
PRACTITIONERS. With Illustrations, Fifth Edition, large 8vo, 21s. [_Just
published._
II.
A PRACTICAL TREATISE ON MATERIA MEDICA AND THERAPEUTICS. Fifth Edition,
Revised and Enlarged, 8vo, 18s. [_Just published._
============
GEO. M. BEARD, A.M., M.D. _Fellow of the New York Academy of Medicine;
Member of the American Academy of Medicine, &c._
AND
A. D. ROCKWELL, A.M., M.D.
_Fellow of the New York Academy of Medicine; Member of the American
Academy of Medicine, &c._
A PRACTICAL TREATISE ON THE MEDICAL AND SURGICAL USES OF ELECTRICITY.
Including Localized and General Faradization; Localized and Central
Galvanization; Franklinization; Electrolysis and Galvano-Cautery. Fourth
Edition. With nearly 200 Illustrations, roy. 8vo, 28s. [_Just
published._
============
A. HUGHES BENNETT, M.D.
_Member of the Royal College of Physicians of London; Physician to the
Hospital for Epilepsy and Paralysis, Regent's Park, and Assistant
Physician to the Westminster Hospital_.
I.
A PRACTICAL TREATISE ON ELECTRO-DIAGNOSIS IN DISEASES OF THE
NERVOUS-SYSTEM. With Illustrations, 8vo, 8s. 6d.
II.
ILLUSTRATIONS OF THE SUPERFICIAL NERVES AND MUSCLES, WITH THEIR MOTOR
POINTS, A knowledge of which is essential in the Art of
Electro-Diagnosis. (Extracted from the above). 8vo, paper cover 1s. 6d.,
cloth 2s.
III.
ON EPILEPSY AND ITS TREATMENT. [_In the press._
============
DR. THEODOR BILLROTH.
_Professor of Surgery in Vienna._
GENERAL SURGICAL PATHOLOGY AND THERAPEUTICS. In Fifty-one Lectures. A
Text-book for Students and Physicians. With additions by Dr. ALEXANDER
VON WINIWARTER, Professor of Surgery in Luttich. Translated from the
Fourth German edition with the special permission of the Author, and
revised from the Tenth edition, by C. E. HACKLEY, A.M., M.D. Copiously
illustrated, 8vo, 18s.
============
G. H. BRANDT, M.D.
I.
ROYAT (LES BAINS) IN AUVERGNE, ITS MINERAL WATERS AND CLIMATE. With
Frontispiece and Map. Second edition, crown 8vo, 2s. 6d.
II.
HAMMAM R'IRHA, ALGIERS. A Winter Health Resort and Mineral Water Cure
Combined. With Frontispiece and Map, crown 8vo, 2s. 6d.
============
GURDON BUCK, M.D.
CONTRIBUTIONS TO REPARATIVE SURGERY; SHOWING its Application to the
Treatment of Deformities, produced by Destructive Disease or Injury;
Congenital Defects from Arrest or Excess of Development; and Cicatricial
Contractions from Burns. Illustrated by numerous Engravings, large 8vo,
9s.
============
ALFRED H. CARTER, M.D. LOND.
_Member of the Royal College of Physicians; Physician to the Queen's
Hospital, Birmingham, &c_.
ELEMENTS OF PRACTICAL MEDICINE. Third Edition, crown 8vo. [_In the
press._
============
P. CAZEAUX.
_Adjunct Professor in the Faculty of Medicine of Paris, &c._
A THEORETICAL AND PRACTICAL TREATISE ON MIDWIFERY INCLUDING THE DISEASES
OF PREGNANCY AND PARTURITION. Revised and Annotated by S. TARNIER.
Translated from the Seventh French Edition by W. R. BULLOCK, M.D. Royal
8vo, Over 1100 pages, 175 Illustrations, 30s.
============
JOHN COCKLE, M.A., M.D.
_Physician to the Royal Free Hospital._
ON INTRA-THORACIC CANCER. 8vo, 4s. 6d.
============
W. H. CORFIELD, M.A., M.D. OXON.
_Professor of Hygiene and Public Health in University College, London._
DWELLING HOUSES: Their Sanitary Construction and Arrangements. Second
Edition, with Illustrations. [_In preparation._
============
J. THOMPSON DICKSON, M.A., M.B. CANTAB.
_Late Lecturer on Mental Diseases at Guy's Hospital._
THE SCIENCE AND PRACTICE OF MEDICINE IN RELATION TO MIND, the Pathology
of the Nerve Centres, and the Jurisprudence of Insanity, being a course
of Lectures delivered at Guy's Hospital. Illustrated by
Chromo-lithographic Drawings and Physiological Portraits. 8vo, 14s.
============
HORACE DOBELL, M.D.
_Consulting Physician to the Royal Hospital for Diseases of the Chest,
&c._
I.
ON DIET AND REGIMEN IN SICKNESS AND HEALTH, and on the Interdependence
and Prevention of Diseases and the Diminution of their Fatality. Seventh
edition, 8vo, 10s. 6d.
II.
AFFECTIONS OF THE HEART AND IN ITS NEIGHBOURHOOD. Cases, Aphorisms, and
Commentaries. Illustrated by the heliotype process, 8vo, 6s. 6d.
============
JOHN EAGLE.
_Member of the Pharmaceutical Society._
A NOTE-BOOK OF SOLUBILITIES. Arranged chiefly for the use of Prescribers
and Dispensers. 12mo, 2s. 6d.
============
JOHN ERIC ERICHSEN.
_Holme Professor of Clinical Surgery in University College; Senior
Surgeon to University College Hospital, &c._
MODERN SURGERY; Its Progress and Tendencies. Being the Introductory
Address delivered at University College at the opening of the Session
1893-74. Demy 8vo, 1s.
============
DR. FERBER.
MODEL DIAGRAM OF THE ORGANS IN THE THORAX AND UPPER PART OF THE ABDOMEN.
With Letter-press Description. In 4to, coloured, 5s.
============
AUSTIN FLINT, JR., M.D.
_Professor of Physiology and Physiological Anatomy in the Bellevue
Medical College, New York; attending Physician to the Bellevue Hospital,
&c._
I.
A TEXT-BOOK OF HUMAN PHYSIOLOGY; DESIGNED for the Use of Practitioners
and Students of Medicine. New edition, Illustrated by plates, and 313
wood engravings, large 8vo, 28s.
II.
THE PHYSIOLOGY OF THE SPECIAL SENSES AND GENERATION; Designed to
Represent the Existing State of Physiological Science, as applied to the
Functions of the Human Body. Being Vol. V of the Physiology of Man. Roy.
8vo, 18s.
============
J. MILNER FOTHERGILL, M.D.
_Member of the Royal College of Physicians of London; Physician to the
City of London Hospital for Diseases of the Chest, Victoria Park, &c._
I.
THE HEART AND ITS DISEASES, WITH THEIR TREATMENT; INCLUDING THE GOUTY
HEART. Second Edition, entirely re-written, copiously illustrated with
woodcuts and lithographic plates. 8vo. 16s.
II.
INDIGESTION, BILIOUSNESS, AND GOUT IN ITS PROTEAN ASPECTS.
PART I.--INDIGESTION AND BILIOUSNESS. Post 8vo, 7s. 6d.
PART II.--GOUT IN ITS PROTEAN ASPECTS. Post 8vo, 7s. 6d.
III.
HEART STARVATION. (Reprinted from the Edinburgh Medical Journal), 8vo,
1s.
============
ERNEST FRANCIS, F.C.S.
_Demonstrator of Practical Chemistry, Charing Cross Hospital._
PRACTICAL EXAMPLES IN QUANTITATIVE ANALYSIS, forming a Concise Guide to
the Analysis of Water, &c. Illustrated, fcap. 8vo, 2s. 6d.
============
HENEAGE GIBBES, M.D.
_Lecturer on Physiology and Histology in the Medical School of
Westminster Hospital; late Curator of the Anatomical Museum at King's
College._
PRACTICAL HISTOLOGY AND PATHOLOGY. Second Edit. revised and enlarged.
Crown 8vo, 5s.
============
C. A. GORDON, M.D., C.B.
_Deputy Inspector General of Hospitals, Army Medical Department_.
REMARKS ON ARMY SURGEONS AND THEIR WORKS. Demy 8vo, 5s.
============
W. R. GOWERS, M.D., F.R.C.P. M.R.C.S.
_Physician to University College Hospital, &c._
DIAGRAMS FOR THE RECORD OF PHYSICAL SIGNS. In books of 12 sets of
figures, 1s. Ditto, unbound, 1s.
============
SAMUEL D. GROSS, M.D., LL.D., D.C.L., OXON.
_Professor of Surgery in the Jefferson Medical College of Philadelphia._
A PRACTICAL TREATISE ON THE DISEASES, INJURIES, AND MALFORMATIONS OF THE
URINARY BLADDER, THE PROSTATE GLAND; AND THE URETHRA. Third Edition,
revised and edited by S. W. GROSS, A.M., M.D., Surgeon to the
Philadelphia Hospital. Illustrated by 170 engravings, 8vo, 18s.
============
SAMUEL W. GROSS, A.M., M.D.
_Surgeon to, and Lecturer on Clinical Surgery in, the Jefferson Medical
College Hospital, and the Philadelphia Hospital, &c._
A PRACTICAL TREATISE ON TUMOURS OF THE MAMMARY GLAND: embracing their
Histology, Pathology, Diagnosis, and Treatment. With Illustrations, 8vo,
10s. 6d.
============
WILLIAM A. HAMMOND, M.D.
_Professor Of Mental and Nervous Diseases in the Medical Department of
the University of the City of New York, &c._
I.
A TREATISE ON THE DISEASES OF THE NERVOUS SYSTEM. Seventh edition, with
112 Illustrations, large 8vo, 25s.
II.
A TREATISE ON INSANITY. Large 8vo, 25s.
[_Just published._
III.
SPIRITUALISM AND ALLIED CAUSES AND CONDITIONS OF NERVOUS DERANGEMENT.
With Illustrations, post 8vo, 8s. 6d.
============
ALEXANDER HARVEY, M.A., M.D.
_Emeritus Professor of Materia Medica in the University of Aberdeen;
Consulting Physician to the Aberdeen Royal Infirmary, &c._
FIRST LINES OF THERAPEUTICS; as based on the Modes and the Processes of
Healing, as occurring Spontaneously in Disease; and on the Modes and the
Processes of Dying, as resulting Naturally from Disease. In a series of
Lectures. Post 8vo, 5s.
============
ALEXANDER HARVEY, M.D.
_Emeritus Professor of Materia Medica in the University of Aberdeen,
&c._
AND
ALEXANDER DYCE DAVIDSON, M.D.
_Professor of Materia Medica in the University of Aberdeen._
SYLLABUS OF MATERIA MEDICA FOR THE USE OF TEACHERS AND STUDENTS. Based
on a selection or definition of subjects in teaching and examining; and
also on an estimate of the relative values of articles and preparations
in the British Pharmacopoeia with doses affixed. Seventh Edition,
32mo.
[_In preparation._
============
GRAILY HEWITT, M.D.
_Professor of Midwifery and Diseases of Women in University College,
Obstetrical Physician to University College Hospital, &c._
OUTLINES OF PICTORIAL DIAGNOSIS OF DISEASES OF WOMEN. Fol. 6s.
============
BERKELEY HILL, M.B. LOND., F.R.C.S.
_Professor of Clinical Surgery in University College; Surgeon to
University College Hospital and to the Lock Hospital._
THE ESSENTIALS OF BANDAGING. For Managing Fractures and Dislocations;
for administering Ether and Chloroform; and for using other Surgical
Apparatus. Fifth Edition, revised and much enlarged, with Illustrations,
fcap. 8vo, 5s.
============
BERKELEY HILL, M.B. LOND., F.R.C.S.
_Professor of Clinical Surgery in University College; Surgeon to
University College Hospital and to the Lock Hospital._
AND
ARTHUR COOPER, L.R.C.P., M.R.C.S.
_Late House Surgeon to the Lock Hospital, &c._
I.
SYPHILIS AND LOCAL CONTAGIOUS DISORDERS. Second Edition, entirely
re-written, royal 8vo, 18s.
II.
THE STUDENT'S MANUAL OF VENEREAL DISEASES. Being a Concise Description
of those Affections and of their Treatment. Third Edition, post 8vo, 2s.
6d.
============
HINTS TO CANDIDATES FOR COMMISSIONS IN THE PUBLIC MEDICAL SERVICES, WITH
EXAMINATION QUESTIONS, VOCABULARY OF HINDUSTANI MEDICAL TERMS, ETC. 8vo,
2s.
============
SIR W. JENNER, Bart., M.D.
_Physician in Ordinary to H. M. the Queen, and to H. R. H. the Prince of
Wales._
THE PRACTICAL MEDICINE OF TO-DAY: Two Addresses delivered before the
British Medical Association, and the Epidemiological Society, (1869).
Small 8vo, 1s. 6d.
============
C. M. JESSOP, M.R.C.P.
_Associate of King's College, London: Brigade Surgeon H.M.'s British
Forces._
ASIATIC CHOLERA, being a Report on an Outbreak of Epidemic Cholera in
1876 at a Camp near Murree in India. With map, demy 8vo, 2s. 6d.
============
GEORGE LINDSAY JOHNSON, M.A., M.B., B.C. CANTAB. _Clinical Assistant,
late House Surgeon and Chloroformist, Royal Westminster Ophthalmic
Hospital; Medical and Surgical Registrar, etc._
A NEW METHOD OF TREATING CHRONIC GLAUCOMA, based on Recent Researches
into its Pathology. With Illustrations and coloured frontispiece, demy
8vo, 3s. 6d.
============
NORMAN W. KINGSLEY, M.D.S., D.D.S.
_President of the Board of Censors of the State of New York; Member of
the American Academy of Dental Science, &c._
A TREATISE ON ORAL DEFORMITIES AS A BRANCH OF MECHANICAL SURGERY. With
over 350 Illustrations, 8vo, 16s.
============
E. A. KIRBY, M.D., M.R.C.S. ENG.
_Late Physician to the City Dispensary._
I.
A PHARMACOPOEIA OF SELECTED REMEDIES, WITH THERAPEUTIC ANNOTATIONS,
Notes on Alimentation in Disease, Air, Massage, Electricity and other
Supplementary Remedial Agents, and a Clinical Index; arranged as a
Handbook for Prescribers. Sixth Edition, enlarged and revised, demy 4to,
7s.
II.
ON THE VALUE OF PHOSPHORUS AS A REMEDY FOR LOSS OF NERVE POWER. Fifth
Edition, 8vo, 2s. 6d.
============
J. WICKHAM LEGG, F.R.C.P.
_Assistant Physician to Saint Bartholomew's Hospital and Lecturer on
Pathological Anatomy in the Medical School_.
I.
ON THE BILE, JAUNDICE, AND BILIOUS DISEASES. With Illustrations in
chroma-lithography, 719 pages, roy. 8vo, 25s.
II.
A GUIDE TO THE EXAMINATION OF THE URINE; intended chiefly for Clinical
Clerks and Students. Fifth Edition, revised and enlarged, with
additional Illustrations, fcap. 8vo, 2s. 6d.
III.
A TREATISE ON HAEMOPHILIA, SOMETIMES CALLED THE HEREDITARY HAEMORRHAGIC
DIATHESIS. Fcap. 4to, 7s. 6d.
============
DR. GEORGE LEWIN.
_Professor at the Fr. With. University, and Surgeon-in-Chief of the
Syphilitic Wards and Skin Disease Wards of the Charite Hospital,
Berlin._
THE TREATMENT OF SYPHILIS WITH SUBCUTANEOUS SUBLIMATE INJECTIONS.
Translated by DR. CARL PROEGLE, and DR. E. H. GALE, _late Surgeon
United States Army_. Small 8vo, 7s.
============
LEWIS'S PRACTICAL SERIES.
Under this title Mr. Lewis purposes publishing a complete Series of
Monographs, embracing the various branches of Medicine and Surgery.
The volumes, written by well-known Hospital Physicians and Surgeons
recognized as authorities in the subjects of which they treat, are in
active preparation. The works are intended to be of a THOROUGHLY
PRACTICAL nature, calculated to meet the requirements of the general
practitioner, and to present the most recent information in a compact
and readable form; the volumes will be handsomely got up, and issued at
low prices, varying with the size of the works.
Several volumes are nearly ready, and further particulars will be
shortly announced.
============
LEWIS'S POCKET MEDICAL VOCABULARY.
[_In the Press._
============
J. S. LOMBARD, M.D.
_Formerly Assistant Professor of Physiology in Harvard College_.
I.
EXPERIMENTAL RESEARCHES ON THE REGIONAL TEMPERATURE OF THE HEAD, under
Conditions of Rest, Intellectual Activity and Emotion. With
Illustrations, 8vo, 8s.
II.
ON THE NORMAL TEMPERATURE OF THE HEAD. 8vo, 5s.
============
WILLIAM THOMPSON LUSK, A.M., M.D.
_Professor of Obstetrics and Diseases of Women in the Bellevue Hospital
Medical College, &c._
THE SCIENCE AND ART OF MIDWIFERY, Second Edition, with numerous
Illustrations, 8vo, 18s.
============
JOHN MACPHERSON, M.D.
_Inspector-General of Hospitals H.M. Bengal Army (Retired). Author of
"Cholera in its Home," &c._
ANNALS OF CHOLERA FROM THE EARLIEST PERIODS TO THE YEAR 1827. With a
map. Demy 8vo, 7s. 6d.
============
DR. V. MAGNAN.
_Physician to St. Anne Asylum, Paris; Laureate of the Institute._
ON ALCOHOLISM, the Various Forms of Alcoholic Delirium and their
Treatment. Translated by W. S. GREENFIELD, M.D., M.R.C.P. 8vo, 7s. 6d.
============
A. COWLEY MALLEY, B.A., M.B., B.CE., T.C.D.
MICRO-PHOTOGRAPHY; including a description of the Wet Collodion and
Gelatino-Bromide Processes, together with the best methods of Mounting
and Preparing Microscopic Objects for Micro-Photography. With
Illustrations and photograph, crown 8vo, 5s.
============
PATRICK MANSON, M.D., C.M.
_Amoy, China._
THE FILARIA SANGUINIS HOMINIS; AND CERTAIN NEW FORMS OF PARASITIC
DISEASE IN INDIA, CHINA, AND WARM COUNTRIES. Illustrated with Plates and
Charts. 8vo, 10s. 6d.
============
PROFESSOR MARTIN.
MARTIN'S ATLAS OF OBSTETRICS AND GYNAECOLOGY. Edited by A. MARTIN, Docent
in the University of Berlin. Translated and edited with additions by
FANCOURT BARNES, M.D., M.R.C.P., Physician to the Chelsea Hospital for
Women; Obstetric Physician to the Great Northern Hospital; and to the
Royal Maternity Charity of London, &c. Medium 4to, Morocco half bound,
31s. 6d. net.
============
WILLIAM MARTINDALE, F.C.S.
_Late Examiner of the Pharmaceutical Society, and late Teacher of
Pharmacy and Demonstrator of Materia Medica at University College._
AND
W. WYNN WESTCOTT, M.B. LOND.
_Deputy Coroner for Central Middlesex._
THE EXTRA PHARMACOPOEIA of Unofficial Drugs and Chemical and
Pharmaceutical Preparations, with References to their Use abstracted
from the Medical Journals and a Therapeutic Index of Diseases and
Symptoms. Third Edition, revised with numerous additions, limp roan,
med. 24mo, 7s., and an edition in fcap. 8vo, with room for marginal
notes, cloth, 7s. [_Now ready._
============
J. F. MEIGS, M.D.
_Consulting Physician in the Children's Hospital, Philadelphia._
AND
W. PEPPER, M.D.
_Lecturer on Clinical Medicine in the University of Pennsylvania._
A PRACTICAL TREATISE ON THE DISEASES OF CHILDREN. Seventh Edition,
revised and enlarged, roy. 8vo, 28s.
============
DR. MORITZ MEYER.
_Royal Counsellor of Health, &c._
ELECTRICITY IN ITS RELATION TO PRACTICAL MEDICINE. Translated from the
Third German Edition, with notes and additions by WILLIAM A. HAMMOND,
M.D. With Illustrations, large 8vo, 18s.
============
Wm. JULIUS MICKLE, M.D., M.R.C.P. LOND.
_Member of the Medico-Psychological Association of Great Britain and
Ireland; member of the Clinical Society, London; Medical Superintendent,
Grove Hall Asylum, London._
GENERAL PARALYSIS OF THE INSANE. 8vo, 10s.
============
KENNETH W. MILLICAN, B.A. CANTAB., M.R.C.S.
THE EVOLUTION OF MORBID GERMS: A Contribution to Transcendental
Pathology. Cr. 8vo, 3s. 6d.
============
E. A. MORSHEAD, M.R.C.S., L.R.C.P.
_Assistant to the Professor of Medicine in University College, London._
TABLES OF THE PHYSIOLOGICAL ACTION OF DRUGS. Fcap, 8vo, 1s.
============
A. STANFORD MORTON, M.B., F.R.C.E. ED.
_Senior Assistant Surgeon, Royal South London Ophthalmic Hospital._
REFRACTION OF THE EYE: Its Diagnosis, and the Correction of its Errors,
with Chapter on Keratoscopy. Second edit., with Illustrations, small
8vo, 2s. 6d.
============
WILLIAM MURRELL, M.D., M.R.C.P., M.R.C.S.
_Lecturer on Materia Medica and Therapeutics at Westminster Hospital;
Senior Assistant Physician, Royal Hospital for Diseases of the Chest._
I.
WHAT TO DO IN CASES OF POISONING. Fourth Edition, revised and enlarged,
royal 32mo.
[_In the press._
II.
NITRO-GLYCERINE AS A REMEDY FOR ANGINA PECTORIS. Crown 8vo, 3s. 6d.
============
WILLIAM NEWMAN, M.D. LOND., F.R.C.S.
_Surgeon to the Stamford Infirmary._
SURGICAL CASES: Mainly from the Wards of the Stamford, Rutland, and
General Infirmary, 8vo, paper boards, 4s. 6d.
============
DR. FELIX von NIEMEYER.
_Late Professor of Pathology and Therapeutics; Director of the Medical
Clinic of the University of Tuebingen._
A TEXT-BOOK OF PRACTICAL MEDICINE, WITH PARTICULAR REFERENCE TO
PHYSIOLOGY AND PATHOLOGICAL ANATOMY. Translated from the Eighth German
Edition, by special permission of the Author, by GEORGE H. HUMPHREY,
M.D., and CHARLES E. HACKLEY, M.D., Revised Edition, 2 vols., large 8vo,
36s.
============
C. F. OLDHAM, M.R.C.S., L.R.C.P.
_Surgeon H.M. Indian Forces; late in Medical charge of the Dalhousie
Sanitarium._
WHAT IS MALARIA? and why is it most intense in hot climates? An
explanation of the Nature and Cause of the so-called Marsh Poison, with
the Principles to be observed for the Preservation of Health in Tropical
Climates and Malarious Districts. Demy 8vo, 7s. 6d.
============
G. OLIVER, M.D., M.R.C.P.
I.
THE HARROGATE WATERS: Data Chemical and Therapeutical, with notes an the
Climate of Harrogate. Addressed to the Medical Profession. Crown 8vo,
with Map of the Wells, 3s. 6d.
II.
ON BEDSIDE URINE TESTING: including Quantitative Albumen and Sugar.
Second edition, revised and enlarged, fcap, 8vo, 2s. 6d.
============
JOHN S. PARRY, M.D.
_Obstetrician to the Philadelphia Hospital, Vice-President of the
Obstetrical and Pathological Societies of Philadelphia, &c._
EXTRA-UTERINE PREGNANCY; Its Causes, Species, Pathological Anatomy.
Clinical History, Diagnosis, Prognosis and Treatment. 8vo, 8s.
============
E. RANDOLPH PEASLEE, M.D., LL.D.
_Late Professor of Gynoecology in the Medical Department of Dartmouth
College; President of the New York Academy of Medicine, &c., &c._
OVARIAN TUMOURS: Their Pathology, Diagnosis, and Treatment, especially
by Ovariotomy. Illustrations, roy. 8vo, 16s.
============
G. V. POORE, M.D., F.R.C.P.
_Professor of Medical Jurisprudence, University College; Assistant
Physician to, and Physician in charge of the Throat Department of
University College Hospital._
LECTURES ON THE PHYSICAL EXAMINATION OF THE MOUTH AND THROAT. With an
Appendix of Cases. 8vo, 3s. 6d.
============
R. DOUGLAS POWELL, M.D., F.R.C.P. LOND.
_Physician to the Middlesex Hospital, and Physician to the Hospital for
Consumption and Diseases of the Chest at Brompton._
DISEASES OF THE LUNGS AND PLEURAE. Third Edition, rewritten and enlarged.
With Illustrations, 8vo.
[_In preparation._
============
AMBROSE L. RANNEY, A.M., M.D.
_Adjunct Professor of Anatomy in the University of New York, etc._
THE APPLIED ANATOMY OF THE NERVOUS SYSTEM, being a study of this portion
of the Human Body from a standpoint of its general interest and
practical utility, designed for use as a Text-book and a Work of
Reference. With 179 Illustrations, 8vo, 20s.
============
RALPH RICHARDSON, M.A., M.D.
_Fellow of the College of Physicians, Edinburgh._
ON THE NATURE OF LIFE: An Introductory Chapter to Pathology. Second
Edition, revised and enlarged. Fcap. 4to, 10s. 6d.
============
W. RICHARDSON, M.A., M.D., M.R.C.P.
REMARKS ON DIABETES, ESPECIALLY IN REFERENCE TO TREATMENT. Demy 8vo, 4s.
6d.
============
SYDNEY RINGER, M.D.
_Professor of the Principles and Practice of Medicine in University
College; Physician to and Professor of Clinical Medicine in, University
College Hospital._
I.
A HANDBOOK OF THERAPEUTICS. Tenth Edition, 8vo, 15s.
II.
ON THE TEMPERATURE OF THE BODY AS A MEANS OF DIAGNOSIS AND PROGNOSIS IN
PHTHISIS. Second Edition, small 8vo, 2s. 6d.
============
FREDERICK T. ROBERTS, M.D., B.SC., F.R.C.P.
_Examiner in Medicine at the Royal College of Surgeon; Professor of
Therapeutics in University College; Physician to University College
Hospital; Physician to Brompton Consumption Hospital, &c._
I.
A HANDBOOK OF THE THEORY AND PRACTICE OF MEDICINE. Fifth Edition, with
Illustrations, in one volume, large 8vo, 21s.
II.
NOTES ON MATERIA MEDICA AND PHARMACY. Fcap. 8vo. [_Nearly ready._
============
D. B. St. JOHN ROOSA, M.A., M.D.
_Professor of Diseases of the Eye and Ear in the University of the City
of New York; Surgeon to the Manhattan Eye and Ear Hospital; Consulting
Surgeon to the Brooklyn Eye and Ear Hospital, &c., &c._
A PRACTICAL TREATISE ON THE DISEASES OF THE EAR, including the Anatomy
of the Organ. Fourth Edition, Illustrated by wood engravings and
chromo-lithographs, large 8vo, 22s.
============
J. BURDON SANDERSON, M.D., LL.D., F.R.S.
_Jodrell Professor of Physiology in University College, London._
UNIVERSITY COLLEGE COURSE OF PRACTICAL EXERCISES IN PHYSIOLOGY. With the
co-operation of F. J. M. PAGE, B.Sc., F.C.S.; W. NORTH, B.A., F.C.S.,
and AUG. WALLER, M.D. Demy 8vo, 3s. 6d.
============
ALDER SMITH, M.B. LOND., F.R.C.S.
_Resident Medical Officer, Christ's Hospital, London._
RINGWORM: Its Diagnosis and Treatment. Second Edition, rewritten and
enlarged. With Illustrations, fcap, 8vo, 4s. 6d.
============
J. LEWIS SMITH, M.D.
_Physician in the New York Infants' Hospital; Clinical Lecturer on
Diseases of Children in Bellevue Hospital Medical College._
A TREATISE ON THE DISEASES OF INFANCY AND CHILDHOOD. Fifth Edition, with
Illustrations, large 8vo, 21s.
============
FRANCIS W. SMITH, M.B., B.S.
THE LEAMINGTON WATERS; CHEMICALLY, THERAPEUTICALLY AND CLINICALLY
CONSIDERED; with observations on the climate of Leamington. With
Illustrations, crown 8vo, 2s. 6d.
============
JAMES STARTIN, M.B., M.R.C.S.
_Surgeon and Joint Lecturer to St. Johns Hospital for Diseases of the
Skin._
LECTURES ON THE PARASITIC DISEASES OF THE SKIN. VEGETOID AND ANIMAL.
With Illustrations, Crown 8vo, 3s. 6d.
============
LEWIS A. STIMSON, B.A., M.D.
_Surgeon to the Presbyterian Hospital; Professor of Pathological Anatomy
in the Medical Faculty of the University of the City of New York._
A MANUAL OF OPERATIVE SURGERY. With three hundred and thirty-two
Illustrations. Post 8vo, 10s. 6d.
============
HUGH OWEN THOMAS, M.R.C.S.
I.
DISEASES OF THE HIP, KNEE, AND ANKLE JOINTS, with their Deformities,
treated by a new and efficient method. With an Introduction by RUSHTON
PARKER, F.R.C.S, Lecturer on Surgery at the School of Medicine,
Liverpool. Third Edition, 8vo, 25s.
II.
CONTRIBUTIONS TO MEDICINE AND SURGERY:--
PART 1.--Intestinal Obstruction; with an Appendix on the Action
of Remedies. 10s.
PART 2.--The Principles of the Treatment of Joint Disease,
Inflammation, Anchylosis, Reduction of Joint Deformity, Bone
Setting. 5s.
PART 5.--On Fractures of the Lower Jaw. 1s.
PART 8.--The Inhibition of Nerves by Drugs. Proof that
Inhibitory Nerve-Fibres do not exist. 1s.
(Parts 3, 4, 6, 7, 9, 10, are expected shortly).
============
J. ASHBURTON THOMPSON, _M.R.C.S._
_Late Surgeon at King's Cross to the Great Northern Railway Company_.
FREE PHOSPHORUS IN MEDICINE WITH SPECIAL REFERENCE TO ITS USE IN
NEURALGIA. A contribution to Materia Medica and Therapeutics. An account
of the History, Pharmaceutical Preparations, Dose, Internal
Administration, and Therapeutic uses of Phosphorus; with a Complete
Bibliography of this subject, referring to nearly 200 works upon it.
Demy 8vo, 7s. 6d.
============
J. C. THOROWGOOD, M.D.
_Assistant Physician to the City of London Hospital for Diseases of the
Chest._
THE CLIMATIC TREATMENT OF CONSUMPTION AND CHRONIC LUNG DISEASES. Third
Edition, post 8vo, 3s. 6d.
============
EDWARD T. TIBBITS, M.D. LOND.
_Physician to the Bradford Infirmary; and to the Bradford Fever
Hospital._
MEDICAL FASHIONS IN THE NINETEENTH CENTURY, including a Sketch of
Bacterio-Mania and the Battle of the Bacilli. Crown 8vo, 2s. 6d.
============
LAURENCE TURNBULL, M.D., PH.G.
_Aural Surgeon to Jefferson Medical College Hospital, &c., &c._
ARTIFICIAL ANAESTHESIA: A Manual of Anaesthetic Agents, and their
Employment in the Treatment of Disease. Second Edition, with
Illustrations, crown 8vo, 6s.
============
W. H. VAN BUREN, M.D., LL.D.
_Professor of Surgery in the Bellevue Hospital Medical College._
DISEASES OF THE RECTUM: And the Surgery of the Lower Bowel. Second
Edition, with Illustrations, 8vo, 14s.
============
RUDOLPH VIRCHOW, M.D.
_Professor in the University, and Member of the Academy of Sciences of
Berlin, &c., &c._
INFECTION--DISEASES IN THE ARMY, Chiefly Wound Fever, Typhoid,
Dysentery, and Diphtheria. Translated from the German by JOHN JAMES,
M.B., F.R.C.S. Fcap. 8vo, 1s. 6d.
============
ALFRED VOGEL, M.D.
_Professor of Clinical Medicine in the University of Dorpat, Russia._
A PRACTICAL TREATISE ON THE DISEASES OF CHILDREN. Translated and Edited
by H. RAPHAEL, M.D. From the Fourth German Edition, illustrated by six
lithographic plates, part coloured, large 8vo, 18s.
============
A. DUNBAR WALKER, M.D., C.M.
THE PARENT'S MEDICAL NOTE BOOK. Oblong post 8vo, cloth, 1s.
============
W. SPENCER WATSON, F.R.C.S. ENG., B.M. LOND.
_Surgeon to the Great Northern Hospital; Surgeon to the Royal South
London Ophthalmic Hospital._
I.
DISEASES OF THE NOSE AND ITS ACCESSORY CAVITIES. Profusely Illustrated.
Demy 8vo, 18s.
II.
EYEBALL-TENSION: Its Effects on the Sight and its Treatment. With
woodcuts, p. 8vo, 2s. 6d.
III.
ON ABSCESS AND TUMOURS OF THE ORBIT. Post 8vo, 2s. 6d.
============
A. DE WATTEVILLE, M.A., M.D., B.SC., M.R.C.S.
_Physician in Charge of the Electro-therapeutical Department at St.
Mary's Hospital._
A PRACTICAL INTRODUCTION TO MEDICAL ELECTRICITY. Second Edition,
re-written and enlarged, copiously Illustrated, 8vo, 9s. [_Just
published._
============
FRANCIS H. WELCH, F.R.C.S.
_Surgeon Major, A.M.D._
ENTERIC FEVER: as Illustrated by Army Data at Home and Abroad, its
Prevalence and Modifications, AEtiology, Pathology and Treatment. 8vo,
5s. 6d.
[_Just published._
============
DR. F. WINCKEL.
_Formerly Professor and Director of the Gynecological Clinic at the
University of Rostock._
THE PATHOLOGY AND TREATMENT OF CHILD-BED: A Treatise for Physicians and
Students. Translated from the Second German edition, with many
additional notes by the Author, by J. R. CHADWICK, M.D. 8vo, 14s.
============
EDWARD WOAKES, M.D. LOND.
_Senior Aural Surgeon and Lecturer on Aural Surgery at the London
Hospital; Senior Surgeon to the Hospital for Diseases of the Throat._
ON DEAFNESS, GIDDINESS AND NOISES IN THE HEAD.
VOL. I.--CATARRH, AND DISEASES OF THE NOSE CAUSING DEAFNESS. With
Illustrations, cr. 8vo, 6s. 6d. [_Just published._
VOL. II.--ON DEAFNESS, GIDDINESS AND NOISES IN THE HEAD. Third Edition,
with Illustrations, cr. 8vo. [_In preparation._
============
E. T. WILSON, B.M. OXON., F.R.C.P. LOND.
_Physician to the Cheltenham General Hospital and Dispensary._
DISINFECTANTS AND HOW TO USE THEM. In Packets of one doz. price 1s.
============
Clinical Charts For Temperature Observations, etc.
Arranged by W. RINDEN, M.R.C.S. Price 7s. per 100, or 1s. per
dozen.
Each Chart is arranged for four weeks, and is ruled at the back
for making notes of cases; they are convenient in size, and are
suitable both for hospital and private practice.
============
PERIODICAL WORKS PUBLISHED BY H. K. LEWIS.
THE NEW SYDENHAM SOCIETY'S PUBLICATIONS. Annual Subscription, One
Guinea.
(Report of the Society, with Complete List of Works and other
information, gratis on application.)
ARCHIVES OF PEDIATRICS. A Monthly Journal, devoted to the Diseases of
Infants and Children. Annual Subscription, 12s. 6d., post free.
THE NEW YORK MEDICAL JOURNAL. A Weekly Review of Medicine. Annual
Subscription, One Guinea, post free.
THE THERAPEUTIC GAZETTE.--A Monthly Journal, devoted to the Science of
Pharmacology, and to the introduction of New Therapeutic Agents. Annual
Subscription, 5s., post free.
THE GLASGOW MEDICAL JOURNAL. Published Monthly. Annual Subscription,
20s., post free. Single numbers, 2s. each.
LIVERPOOL MEDICO-CHIRURGICAL JOURNAL, including the Proceedings of the
Liverpool Medical Institution. Published twice yearly, 3s. 6d. each.
THE MIDLAND MEDICAL MISCELLANY AND PROVINCIAL MEDICAL JOURNAL. Annual
Subscription, 7s. 6d., post free.
TRANSACTIONS OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Volumes I to
VI., now ready, 8vo, 10s. 6d. each.
============
*** MR. LEWIS has transactions with the leading publishing firms in
America for the sale of his publications in that country. Arrangements
are made in the interests of Authors either for sending a number of
copies of their works to the United States, or having them reprinted
there, as may be most advantageous.
Mr. Lewis's publications can be procured of any bookseller in any part
of the world.
============
London: Printed by H. K. Lewis, 196 Gower Street, W.C.
Transcriber's Notes
[***] is used to replace an asterism.
============ 12 equal signs replace horizontal rules in text.
The words 'rewritten' and 're-written' are used interchangeably.
Page 15
(In the inter-paroxysmal state). Changed 'interparoxysmal' to
'inter-paroxysmal'.
Page 22
( 11 8 -- 3). Changed duplicate case
'12' to case '11'.
Page 27
(were diminished in number). Changed 'dimished' to 'diminished'.
Page 34
(4. In 2.3 per cent. the number). Changed duplicate label from '3.' to
'4.'.
Page 45
(and treatment on the other,). Changed 'treatmeat' to 'treatment'.
(symptoms directly attributable). Changed 'attribuable' to
'attributable'.
Page 47
(long-continued absence). Changed 'continned' to 'continued'.
Advertisements
Page 10
(GERMS: A contribution). Changed 'Contribu-bution' to 'Contribution'.
End of the Project Gutenberg EBook of A Statistical Inquiry Into the Nature
and Treatment of Epilepsy, by Alexander Hughes Bennett
*** END OF THIS PROJECT GUTENBERG EBOOK STATISTICAL INQUIRY--EPILEPSY ***
***** This file should be named 36474.txt or 36474.zip *****
This and all associated files of various formats will be found in:
https://www.gutenberg.org/3/6/4/7/36474/
Produced by Bryan Ness, Leonard Johnson and the Online
Distributed Proofreading Team at https://www.pgdp.net (This
book was produced from scanned images of public domain
material from the Google Print project.)
Updated editions will replace the previous one--the old editions
will be renamed.
Creating the works from public domain print editions means that no
one owns a United States copyright in these works, so the Foundation
(and you!) can copy and distribute it in the United States without
permission and without paying copyright royalties. Special rules,
set forth in the General Terms of Use part of this license, apply to
copying and distributing Project Gutenberg-tm electronic works to
protect the PROJECT GUTENBERG-tm concept and trademark. Project
Gutenberg is a registered trademark, and may not be used if you
charge for the eBooks, unless you receive specific permission. If you
do not charge anything for copies of this eBook, complying with the
rules is very easy. You may use this eBook for nearly any purpose
such as creation of derivative works, reports, performances and
research. They may be modified and printed and given away--you may do
practically ANYTHING with public domain eBooks. Redistribution is
subject to the trademark license, especially commercial
redistribution.
*** START: FULL LICENSE ***
THE FULL PROJECT GUTENBERG LICENSE
PLEASE READ THIS BEFORE YOU DISTRIBUTE OR USE THIS WORK
To protect the Project Gutenberg-tm mission of promoting the free
distribution of electronic works, by using or distributing this work
(or any other work associated in any way with the phrase "Project
Gutenberg"), you agree to comply with all the terms of the Full Project
Gutenberg-tm License (available with this file or online at
https://gutenberg.org/license).
Section 1. General Terms of Use and Redistributing Project Gutenberg-tm
electronic works
1.A. By reading or using any part of this Project Gutenberg-tm
electronic work, you indicate that you have read, understand, agree to
and accept all the terms of this license and intellectual property
(trademark/copyright) agreement. If you do not agree to abide by all
the terms of this agreement, you must cease using and return or destroy
all copies of Project Gutenberg-tm electronic works in your possession.
If you paid a fee for obtaining a copy of or access to a Project
Gutenberg-tm electronic work and you do not agree to be bound by the
terms of this agreement, you may obtain a refund from the person or
entity to whom you paid the fee as set forth in paragraph 1.E.8.
1.B. "Project Gutenberg" is a registered trademark. It may only be
used on or associated in any way with an electronic work by people who
agree to be bound by the terms of this agreement. There are a few
things that you can do with most Project Gutenberg-tm electronic works
even without complying with the full terms of this agreement. See
paragraph 1.C below. There are a lot of things you can do with Project
Gutenberg-tm electronic works if you follow the terms of this agreement
and help preserve free future access to Project Gutenberg-tm electronic
works. See paragraph 1.E below.
1.C. The Project Gutenberg Literary Archive Foundation ("the Foundation"
or PGLAF), owns a compilation copyright in the collection of Project
Gutenberg-tm electronic works. Nearly all the individual works in the
collection are in the public domain in the United States. If an
individual work is in the public domain in the United States and you are
located in the United States, we do not claim a right to prevent you from
copying, distributing, performing, displaying or creating derivative
works based on the work as long as all references to Project Gutenberg
are removed. Of course, we hope that you will support the Project
Gutenberg-tm mission of promoting free access to electronic works by
freely sharing Project Gutenberg-tm works in compliance with the terms of
this agreement for keeping the Project Gutenberg-tm name associated with
the work. You can easily comply with the terms of this agreement by
keeping this work in the same format with its attached full Project
Gutenberg-tm License when you share it without charge with others.
1.D. The copyright laws of the place where you are located also govern
what you can do with this work. Copyright laws in most countries are in
a constant state of change. If you are outside the United States, check
the laws of your country in addition to the terms of this agreement
before downloading, copying, displaying, performing, distributing or
creating derivative works based on this work or any other Project
Gutenberg-tm work. The Foundation makes no representations concerning
the copyright status of any work in any country outside the United
States.
1.E. Unless you have removed all references to Project Gutenberg:
1.E.1. The following sentence, with active links to, or other immediate
access to, the full Project Gutenberg-tm License must appear prominently
whenever any copy of a Project Gutenberg-tm work (any work on which the
phrase "Project Gutenberg" appears, or with which the phrase "Project
Gutenberg" is associated) is accessed, displayed, performed, viewed,
copied or distributed:
This eBook is for the use of anyone anywhere at no cost and with
almost no restrictions whatsoever. You may copy it, give it away or
re-use it under the terms of the Project Gutenberg License included
with this eBook or online at www.gutenberg.org
1.E.2. If an individual Project Gutenberg-tm electronic work is derived
from the public domain (does not contain a notice indicating that it is
posted with permission of the copyright holder), the work can be copied
and distributed to anyone in the United States without paying any fees
or charges. If you are redistributing or providing access to a work
with the phrase "Project Gutenberg" associated with or appearing on the
work, you must comply either with the requirements of paragraphs 1.E.1
through 1.E.7 or obtain permission for the use of the work and the
Project Gutenberg-tm trademark as set forth in paragraphs 1.E.8 or
1.E.9.
1.E.3. If an individual Project Gutenberg-tm electronic work is posted
with the permission of the copyright holder, your use and distribution
must comply with both paragraphs 1.E.1 through 1.E.7 and any additional
terms imposed by the copyright holder. Additional terms will be linked
to the Project Gutenberg-tm License for all works posted with the
permission of the copyright holder found at the beginning of this work.
1.E.4. Do not unlink or detach or remove the full Project Gutenberg-tm
License terms from this work, or any files containing a part of this
work or any other work associated with Project Gutenberg-tm.
1.E.5. Do not copy, display, perform, distribute or redistribute this
electronic work, or any part of this electronic work, without
prominently displaying the sentence set forth in paragraph 1.E.1 with
active links or immediate access to the full terms of the Project
Gutenberg-tm License.
1.E.6. You may convert to and distribute this work in any binary,
compressed, marked up, nonproprietary or proprietary form, including any
word processing or hypertext form. However, if you provide access to or
distribute copies of a Project Gutenberg-tm work in a format other than
"Plain Vanilla ASCII" or other format used in the official version
posted on the official Project Gutenberg-tm web site (www.gutenberg.org),
you must, at no additional cost, fee or expense to the user, provide a
copy, a means of exporting a copy, or a means of obtaining a copy upon
request, of the work in its original "Plain Vanilla ASCII" or other
form. Any alternate format must include the full Project Gutenberg-tm
License as specified in paragraph 1.E.1.
1.E.7. Do not charge a fee for access to, viewing, displaying,
performing, copying or distributing any Project Gutenberg-tm works
unless you comply with paragraph 1.E.8 or 1.E.9.
1.E.8. You may charge a reasonable fee for copies of or providing
access to or distributing Project Gutenberg-tm electronic works provided
that
- You pay a royalty fee of 20% of the gross profits you derive from
the use of Project Gutenberg-tm works calculated using the method
you already use to calculate your applicable taxes. The fee is
owed to the owner of the Project Gutenberg-tm trademark, but he
has agreed to donate royalties under this paragraph to the
Project Gutenberg Literary Archive Foundation. Royalty payments
must be paid within 60 days following each date on which you
prepare (or are legally required to prepare) your periodic tax
returns. Royalty payments should be clearly marked as such and
sent to the Project Gutenberg Literary Archive Foundation at the
address specified in Section 4, "Information about donations to
the Project Gutenberg Literary Archive Foundation."
- You provide a full refund of any money paid by a user who notifies
you in writing (or by e-mail) within 30 days of receipt that s/he
does not agree to the terms of the full Project Gutenberg-tm
License. You must require such a user to return or
destroy all copies of the works possessed in a physical medium
and discontinue all use of and all access to other copies of
Project Gutenberg-tm works.
- You provide, in accordance with paragraph 1.F.3, a full refund of any
money paid for a work or a replacement copy, if a defect in the
electronic work is discovered and reported to you within 90 days
of receipt of the work.
- You comply with all other terms of this agreement for free
distribution of Project Gutenberg-tm works.
1.E.9. If you wish to charge a fee or distribute a Project Gutenberg-tm
electronic work or group of works on different terms than are set
forth in this agreement, you must obtain permission in writing from
both the Project Gutenberg Literary Archive Foundation and Michael
Hart, the owner of the Project Gutenberg-tm trademark. Contact the
Foundation as set forth in Section 3 below.
1.F.
1.F.1. Project Gutenberg volunteers and employees expend considerable
effort to identify, do copyright research on, transcribe and proofread
public domain works in creating the Project Gutenberg-tm
collection. Despite these efforts, Project Gutenberg-tm electronic
works, and the medium on which they may be stored, may contain
"Defects," such as, but not limited to, incomplete, inaccurate or
corrupt data, transcription errors, a copyright or other intellectual
property infringement, a defective or damaged disk or other medium, a
computer virus, or computer codes that damage or cannot be read by
your equipment.
1.F.2. LIMITED WARRANTY, DISCLAIMER OF DAMAGES - Except for the "Right
of Replacement or Refund" described in paragraph 1.F.3, the Project
Gutenberg Literary Archive Foundation, the owner of the Project
Gutenberg-tm trademark, and any other party distributing a Project
Gutenberg-tm electronic work under this agreement, disclaim all
liability to you for damages, costs and expenses, including legal
fees. YOU AGREE THAT YOU HAVE NO REMEDIES FOR NEGLIGENCE, STRICT
LIABILITY, BREACH OF WARRANTY OR BREACH OF CONTRACT EXCEPT THOSE
PROVIDED IN PARAGRAPH 1.F.3. YOU AGREE THAT THE FOUNDATION, THE
TRADEMARK OWNER, AND ANY DISTRIBUTOR UNDER THIS AGREEMENT WILL NOT BE
LIABLE TO YOU FOR ACTUAL, DIRECT, INDIRECT, CONSEQUENTIAL, PUNITIVE OR
INCIDENTAL DAMAGES EVEN IF YOU GIVE NOTICE OF THE POSSIBILITY OF SUCH
DAMAGE.
1.F.3. LIMITED RIGHT OF REPLACEMENT OR REFUND - If you discover a
defect in this electronic work within 90 days of receiving it, you can
receive a refund of the money (if any) you paid for it by sending a
written explanation to the person you received the work from. If you
received the work on a physical medium, you must return the medium with
your written explanation. The person or entity that provided you with
the defective work may elect to provide a replacement copy in lieu of a
refund. If you received the work electronically, the person or entity
providing it to you may choose to give you a second opportunity to
receive the work electronically in lieu of a refund. If the second copy
is also defective, you may demand a refund in writing without further
opportunities to fix the problem.
1.F.4. Except for the limited right of replacement or refund set forth
in paragraph 1.F.3, this work is provided to you 'AS-IS' WITH NO OTHER
WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO
WARRANTIES OF MERCHANTIBILITY OR FITNESS FOR ANY PURPOSE.
1.F.5. Some states do not allow disclaimers of certain implied
warranties or the exclusion or limitation of certain types of damages.
If any disclaimer or limitation set forth in this agreement violates the
law of the state applicable to this agreement, the agreement shall be
interpreted to make the maximum disclaimer or limitation permitted by
the applicable state law. The invalidity or unenforceability of any
provision of this agreement shall not void the remaining provisions.
1.F.6. INDEMNITY - You agree to indemnify and hold the Foundation, the
trademark owner, any agent or employee of the Foundation, anyone
providing copies of Project Gutenberg-tm electronic works in accordance
with this agreement, and any volunteers associated with the production,
promotion and distribution of Project Gutenberg-tm electronic works,
harmless from all liability, costs and expenses, including legal fees,
that arise directly or indirectly from any of the following which you do
or cause to occur: (a) distribution of this or any Project Gutenberg-tm
work, (b) alteration, modification, or additions or deletions to any
Project Gutenberg-tm work, and (c) any Defect you cause.
Section 2. Information about the Mission of Project Gutenberg-tm
Project Gutenberg-tm is synonymous with the free distribution of
electronic works in formats readable by the widest variety of computers
including obsolete, old, middle-aged and new computers. It exists
because of the efforts of hundreds of volunteers and donations from
people in all walks of life.
Volunteers and financial support to provide volunteers with the
assistance they need are critical to reaching Project Gutenberg-tm's
goals and ensuring that the Project Gutenberg-tm collection will
remain freely available for generations to come. In 2001, the Project
Gutenberg Literary Archive Foundation was created to provide a secure
and permanent future for Project Gutenberg-tm and future generations.
To learn more about the Project Gutenberg Literary Archive Foundation
and how your efforts and donations can help, see Sections 3 and 4
and the Foundation web page at https://www.pglaf.org.
Section 3. Information about the Project Gutenberg Literary Archive
Foundation
The Project Gutenberg Literary Archive Foundation is a non profit
501(c)(3) educational corporation organized under the laws of the
state of Mississippi and granted tax exempt status by the Internal
Revenue Service. The Foundation's EIN or federal tax identification
number is 64-6221541. Its 501(c)(3) letter is posted at
https://pglaf.org/fundraising. Contributions to the Project Gutenberg
Literary Archive Foundation are tax deductible to the full extent
permitted by U.S. federal laws and your state's laws.
The Foundation's principal office is located at 4557 Melan Dr. S.
Fairbanks, AK, 99712., but its volunteers and employees are scattered
throughout numerous locations. Its business office is located at
809 North 1500 West, Salt Lake City, UT 84116, (801) 596-1887, email
business@pglaf.org. Email contact links and up to date contact
information can be found at the Foundation's web site and official
page at https://pglaf.org
For additional contact information:
Dr. Gregory B. Newby
Chief Executive and Director
gbnewby@pglaf.org
Section 4. Information about Donations to the Project Gutenberg
Literary Archive Foundation
Project Gutenberg-tm depends upon and cannot survive without wide
spread public support and donations to carry out its mission of
increasing the number of public domain and licensed works that can be
freely distributed in machine readable form accessible by the widest
array of equipment including outdated equipment. Many small donations
($1 to $5,000) are particularly important to maintaining tax exempt
status with the IRS.
The Foundation is committed to complying with the laws regulating
charities and charitable donations in all 50 states of the United
States. Compliance requirements are not uniform and it takes a
considerable effort, much paperwork and many fees to meet and keep up
with these requirements. We do not solicit donations in locations
where we have not received written confirmation of compliance. To
SEND DONATIONS or determine the status of compliance for any
particular state visit https://pglaf.org
While we cannot and do not solicit contributions from states where we
have not met the solicitation requirements, we know of no prohibition
against accepting unsolicited donations from donors in such states who
approach us with offers to donate.
International donations are gratefully accepted, but we cannot make
any statements concerning tax treatment of donations received from
outside the United States. U.S. laws alone swamp our small staff.
Please check the Project Gutenberg Web pages for current donation
methods and addresses. Donations are accepted in a number of other
ways including including checks, online payments and credit card
donations. To donate, please visit: https://pglaf.org/donate
Section 5. General Information About Project Gutenberg-tm electronic
works.
Professor Michael S. Hart was the originator of the Project Gutenberg-tm
concept of a library of electronic works that could be freely shared
with anyone. For thirty years, he produced and distributed Project
Gutenberg-tm eBooks with only a loose network of volunteer support.
Project Gutenberg-tm eBooks are often created from several printed
editions, all of which are confirmed as Public Domain in the U.S.
unless a copyright notice is included. Thus, we do not necessarily
keep eBooks in compliance with any particular paper edition.
Most people start at our Web site which has the main PG search facility:
https://www.gutenberg.org
This Web site includes information about Project Gutenberg-tm,
including how to make donations to the Project Gutenberg Literary
Archive Foundation, how to help produce our new eBooks, and how to
subscribe to our email newsletter to hear about new eBooks.
|