- Email: [email protected]
Varicoceles in young soccer players
THE LANCET
prolonged prophylaxis with enoxaparin was shown to offer protection. However, after 4–5 weeks’ prophylaxis, a meaningful number of patients are still presenting with proximal DVT. Although our conclusion remains that prolonged prophylaxis is necessary in hip replacement patients, the optimum duration of this prophylaxis and the clinical relevance of DVTs observed at day 35 post-surgery are still unresolved issues. Overall, the frequency of day 35 post-surgery venographically detected DVTs did not differ between patients who received general anaesthesia (n=16/101) and those who received regional anaesthesia (n=7/72; p=0·243). Reviewing our data, we found that 35/85 patients in the enoxaparin group and 37/88 patients in the placebo group received regional anaesthesia. In patients with general anaesthesia, the rate of DVT was 4/50 (8%) in the enoxaparin group versus 12/51 (23·53%) in the placebo group. In patients with regional anaesthesia, the corresponding rates were 2/35 (5·71%) and 5/37 (13·51%). However, the fact that patients were not randomised according to the type of anaesthesia and the small number of cases observed in subgroups mean that these results should be interpreted very cautiously. *A Planes, N Vochelle, J Y Darman
duration of post-discharge follow-up was 7·9 weeks (range 4–12). Our review showed a low frequency of clinically overt venous thromboembolism at follow-up after major orthopaedic venography. We share ten Cate and Prins’ opinion that large, clinical end-point trials with strict criteria for outcome detection are needed before setting guidelines for the optimum duration of post-operative pharmacological prophylaxis. Venous thrombi leading to hospital readmission are likely to be present but symptomless at the time of discharge and to become symptomatic afterwards. Unfortunately, because of the poor sensitivity of the available non-invasive diagnostic methods for screening symptomless DVT, 4 venography is the only accurate diagnostic method in this clinical setting. Future research should be directed to improving the accuracy of noninvasive diagnostic methods to replace venography in the screening of symptomless postoperative DVT. *Giancarlo Agnelli, Alfonso Iorio, Serena Ricotta, Pasquale Parise, Giuseppe G Nenci Istituto di Medicina Interna e Vascolare, Università di Perugia, 06122 Perugia, Italy
1
Clinique Radio-chirurgicale du Mail, 17028 La Rochette, France
1
2 3
US National Institutes of Health. Consensus Conference on the prevention of venous thrombosis and pulmonary embolism. JAMA 1986; 256: 744–49. ten Cate JW Prins MH. Major orthopaedic surgery and post-discharge DVT. Lancet 1996; 348: 209–10. Bergqvist D, Benoni G, Bjôrgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696–700.
SIR—Planes and colleagues1 and ten Cate and Prins (July 27, p 209)2 draw further attention to the unresolved and controversial issues of the occurrence of post-discharge venous thromboembolism in patients undergoing orthopaedic surgery and of the optimum duration of pharmacological prophylaxis. In patients discharged with a negative venogram a high frequency of venographyconfirmed DVT was recorded 3 weeks after discharge.1 Enoxaparin continued after discharge was effective in reducing the rate of DVT. At 3-month follow-up the rate of clinically overt thromboembolic events was 0·58%. We do not know whether thrombi detected by venography 35 days after surgery, but not causing symptoms, are clinically important. In fact, follow-up studies, including one from our group,3 showed a low rate of clinically overt thromboembolic events in patients discharged with negative venography. We carried out a literature review of the frequency of post-discharge clinically overt venous thromboembolism after orthopaedic surgery. We examined the studies published from January, 1974, to December, 1995, on the prophylaxis of venous thromboembolism after major orthopaedic surgery fulfilling the following criteria: (1) pharmacological prophylaxis restricted to the hospital stay; (2) bilateral venography before discharge; and (3) postdischarge follow-up of the patients for at least 4 weeks. Of 31 identified studies, 13 fulfilled the overview criteria. The total number of patients evaluated was 4120. An adequate venogram was obtained before discharge in 3469 patients (84%). In the 2361 patients with negative venography (68%), 30 episodes of symptomatic venous thromboembolism after hospital discharge were reported, with a resulting cumulative frequency of 1·27% (95% CI 0·82–1·72). Six of these 30 cases of DVT showed pulmonary embolism, which was fatal in one. The average
1180
2 3
4
Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348: 224–28. ten Cate JW, Prins MH. Major orthopaedic surgery and postdischarge DVT. Lancet 1996; 348: 209–10. Agnelli G, Ranucci V, Veschi F, Rinonapoli E, Lupattelli L, Nenci CG. Clinical outcome of hip surgery patients with negative lower limb venography at discharge. Thromb Haemost 1995; 74: 1042–44. Agnelli G, Radicchia S, Nenci CG. The diagnosis of deep vein thrombosis in asymptomatic high risk patients. Haemostasis 1995; 25: 40–48.
Varicoceles in young soccer players SIR—Varicocele is common in adolescence, though reports of its prevalence are conflicting.1,2 The aetiology is still largely unknown. Varicocele usually causes no symptoms, and is usually detected on routine physical examination of healthy children. We looked for varicocele in 198 healthy boys aged 10–14 years who were schoolchildren or young elite soccer players. 30 were sedentary, 19 trained 1–3 hours/week, 58 trained 4–6 hours/week, 18 trained 7–9 hours/week, and 73 trained for more than 10 hours/week. Height, weight, and pubertal stage according to Tanner were evaluated. Physical examination for varicocele was done by one investigator (AS) by palpating the spermatic cords with the boy standing up before and during a Valsalva manoeuvre; testicular size was measured with an orchidometer. The overall prevalence of varicocele (all left-sided) was 17·7% (35/198): 21/198 grade I (10·6%), 11/198 grade II (5·5%), and 3/198 grade III (1·5%). Prevalence of varicocele by degree of sports training is shown in the table. No difference was observed for age, height, weight, and pubertal stage. In the group who exercised more than 10 hours/week (the only group for which statistical analysis is reliable) the patients with varicocele showed a significant difference in testicular volume (right: 7·42 [SD 2·9] vs left: 6·72 [2·70] mL, p=0·01), while patients without varicocele did not (right: 8·97 [4·70] vs 8·81 [4·64] mL). We are unaware of any similar reports. Sports training might cause varicocele by some mechanical effects of exercise. Because varicocele can cause subfertility3 and prognosis for fertility will deteriorate if the varicocele persists,4 our findings suggest that a careful examination be
Vol 348 • October 26, 1996
THE LANCET
Sports training (hours/wk)
Number
Age (years mean [SD])
Height (cm mean [SD])
Weight (kg, mean [SD])
Pubertal stage
Varicocele all n (%)
Grade I n (%)
Grade II n (%)
Grade III n (%)
0 1–3 4–6 7–9 肁10
30 19 58 18 73
12·2 (1·0) 12·3 (1·2) 12·4 (1·0) 12·3 (1·0) 12·5 (0·9)
155 (7) 157 (5) 157 (6) 156 (8) 159 (8)
47 (9) 45 (5) 46 (4) 46 (3) 45 (5)
1–5 1–5 1–5 1–5 1–5
0 (0) 2 (10·5) 8 (13·8) 4 (22·2) 21 (28·8)
0 (0) 1 (5·2) 5 (8·6) 2 (11·1) 13 (17·8)
0 (0) 1 (5·3) 3 (5·1) 2 (11·1) 6 (8·2)
0 (0) 0 (0) 0 (0) 0 (0) 3 (4·1)*
*The 3 subjects with grade III underwent varicocele correction.
Table: Prevalence of varicocele in the 198 healthy adolescents
done of all adolescent athletes to detect and correct early,2 this important risk factor for future fertility. We thank the pupils of C Angelini Junior High School at Pavia and young soccer players of Milan AC, AC Pro Sesto, AC Monza, and AC Pavia; and G Levizzanmi (Milan AC), B Costantino (AC Pro Sesto), and L Besana (AC Monza) for their collaboration.
*Andrea Scaramuzza, Rodolfo Tavana, Antonietta Marchi Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Pavia; *Division of Pediatrics, Azienda Istituti Ospitalieri, I-26100 Cremona; and Medical Staff of Milan AC, Milan, Italy
1
2 3 4
Belloli G, D’Agostino S, Pesce C, Fantuz E. Adolescent varicocele and other testicular anomalies: an epidemiologic study. Med Surg Ped 1993; 15: 159–62. Kass EJ, Reitelman C. Adolescent varicocele. Urol Clin North Am 1995; 22: 151–59. Goldstein M. Adolescent varicocele. J Urol 1995; 153: 484–85. Hienz HA, Voggenthaler J, Weissbach L. Histological findings in testes with varicocele during childhood and their therapeutic consequences. Eur J Pediatr 1980; 133:139–46.
Resurgence of Vibrio cholerae O139 Bengal with altered antibiogram in Calcutta, India SIR—1992 saw the emergence in southern India of a novel serogroup currently classified as Vibrio cholerae O139 Bengal. On the basis of this microorganism’s ability to spread rapidly through cholera endemic areas in India and in neighbouring countries and on the propensity of the new serogroup to replace the O1 El Tor biotype, V cholerae O139 was described as the new pandemic strain of cholera.1 Surprisingly, however, in the subsequent years the El Tor biotype reappeared in most parts of the Indian subcontinent, replaced O139, and again became the dominant serogroup causing cholera (table).2 The reappearance of El Tor and the decline in O139 in the Indian subcontinent led investigators to believe that the emergence of O139 serogroup had been a one-time event. Continuing surveillance on V cholerae in Calcutta now reveals the resurgence of O139 since August, 1996. As of Sept 20, 1996, the monthly isolation rate of V cholerae O139 (59·7%) has exceeded that of O1 serogroup (30·6%) for the first time since November, 1993, in Calcutta (table). Of the 20 recent strains of V cholerae O139 examined, all were resistant to ampicillin and furazolidone; 95%, 85%, and 25% were resistant to neomycin, streptomycin, and tetracycline, respectively; and 10% of the strains were resistant to Year
1993 1994 1995 1996
Month(s)
Jan–June July–Dec Jan–June July–Dec Jan–June July–Dec Jan–June July Aug Sept
No (%) of V cholerae isolated O1
O139
Non-O1, non-O139
0 23 (9·9) 126 (69·2) 169 (77·5) 137 (84·9) 168 (71·2) 114 (72·6) 37 (72·5) 37 (62·7) 19 (30·6)
246 (94·9) 197 (84·9) 35 (19·2) 32 (14·7) 10 (6·1) 52 (22·0) 2 (1·3) 1 (1·9) 16 (27·1) 37 (59·7)
13 (5·1) 12 (5·2) 21 (11·6) 17 (7·8) 16 (9·8) 16 (6·8) 41 (26·1) 13 (25·6) 6 (10·2) 6 (9·7)
Table: Isolation of various serogroups of V cholerae from patients admitted because of acute secretory diarrhoea to Infectious Diseases Hospital, Calcutta
Vol 348 • October 26, 1996
gentamicin and nalidixic acid. All strains tested were susceptible to chloramphenicol, ciprofloxacin, cotrimoxazole, and norfloxacin. All strains were also sensitive to the vibriostatic agent pteridine. Therefore, unlike the O139 strains which emerged in November, 1992, in Calcutta,3 the current O139 isolates are sensitive to cotrimoxazole and pteridine, and the antibiogram of the current O139 differs from that of O139 isolated in 1992–93. We tested recent strains of V cholerae O139 by polymerase chain amplification to determine the presence of ctxA (encoding the enzymatic subunit of cholera toxin), zot (zonula occludens toxin), ace (accessory cholera toxin), and tcpA (major structural subunit of toxin coregulated pili). All the O139 strains examined were positive for the 301 bp ctxA, 243 bp zot, and 284 bp ace amplicons and also for the 471 bp tcpA amplicon, indicating that the genes comprising the virulence cassette and the gene encoding for the surface organelles required for intestinal colonisation were intact. The resurgence of O139 seems not to be limited to Calcutta since we have recently received O139 strains from Madras. The current resurgence could be a prelude to what happened in 1992 and efforts must again be initiated to monitor and control the spread of O139 at a global level. Rupak Mitra, Arnab Basu, D Dutta, *G Balakrish Nair, Yoshifumi Takeda *National Institute of Cholera and Enteric Diseases, Beliaghata, Calcutta-700 010, India; and Research Institute, International Medical Center of Japan, Tokyo
1 2
3
Nair GB, Ramamurthy T, Bhattacharya SK, et al. Spread of Vibrio cholerae O139 Bengal in India. J Infect Dis 1994; 169: 1029–34. Mukhopadhyay AK, Garg S, Mitra R, et al. Temporal shifts in traits of Vibrio cholerae strains isolated from hospitalized patients in Calcutta: a 3-year (1993 to 1995) analysis. J Clin Microbiol 1996; 34: 2537–43. Ramamurthy T, Garg S, Sharma R, et al. Emergence of novel strain of Vibrio cholerae with epidemic potential in southern and eastern India. Lancet 1993; 341: 703–04.
Long-term tacrine treatment in Alzheimer’s disease SIR—Solomon and colleagues (July 27, p 275)1 conclude that long-term tacrine could produce a continued symptomatic benefit for patients with Alzheimer’s disease remaining in treatment for almost 2 years. Their figure shows that after an initial improvement on the cognitive portion of the Alzheimer’s disease assessment scale (ADAS-Cog) of 2·6 points in tacrine-treated patients (5–9 months of therapy), a sustained decline that parallels the control group was seen for 11–15 and 17–21 months of treatment. We disagree that the initial delay of disease progression demonstrates a sustained efficacy beyond 5–9 months. In fact, the possible benefits of tacrine therapy on ADAS-Cog disappeared despite its continuous administration for several months. The study has also serious methodological drawbacks (small sample, non-randomised, non-blind drug administration and evaluation, possibly biased selection of controls) that could invalidate their findings. To support their results, they refer to published studies1–3 that unfortunately share some of these methodological problems. The results of Solomon and colleagues’ pilot study could be the basis for a hypothesis justifying the necessity of clinical
1181
prolonged prophylaxis with enoxaparin was shown to offer protection. However, after 4–5 weeks’ prophylaxis, a meaningful number of patients are still presenting with proximal DVT. Although our conclusion remains that prolonged prophylaxis is necessary in hip replacement patients, the optimum duration of this prophylaxis and the clinical relevance of DVTs observed at day 35 post-surgery are still unresolved issues. Overall, the frequency of day 35 post-surgery venographically detected DVTs did not differ between patients who received general anaesthesia (n=16/101) and those who received regional anaesthesia (n=7/72; p=0·243). Reviewing our data, we found that 35/85 patients in the enoxaparin group and 37/88 patients in the placebo group received regional anaesthesia. In patients with general anaesthesia, the rate of DVT was 4/50 (8%) in the enoxaparin group versus 12/51 (23·53%) in the placebo group. In patients with regional anaesthesia, the corresponding rates were 2/35 (5·71%) and 5/37 (13·51%). However, the fact that patients were not randomised according to the type of anaesthesia and the small number of cases observed in subgroups mean that these results should be interpreted very cautiously. *A Planes, N Vochelle, J Y Darman
duration of post-discharge follow-up was 7·9 weeks (range 4–12). Our review showed a low frequency of clinically overt venous thromboembolism at follow-up after major orthopaedic venography. We share ten Cate and Prins’ opinion that large, clinical end-point trials with strict criteria for outcome detection are needed before setting guidelines for the optimum duration of post-operative pharmacological prophylaxis. Venous thrombi leading to hospital readmission are likely to be present but symptomless at the time of discharge and to become symptomatic afterwards. Unfortunately, because of the poor sensitivity of the available non-invasive diagnostic methods for screening symptomless DVT, 4 venography is the only accurate diagnostic method in this clinical setting. Future research should be directed to improving the accuracy of noninvasive diagnostic methods to replace venography in the screening of symptomless postoperative DVT. *Giancarlo Agnelli, Alfonso Iorio, Serena Ricotta, Pasquale Parise, Giuseppe G Nenci Istituto di Medicina Interna e Vascolare, Università di Perugia, 06122 Perugia, Italy
1
Clinique Radio-chirurgicale du Mail, 17028 La Rochette, France
1
2 3
US National Institutes of Health. Consensus Conference on the prevention of venous thrombosis and pulmonary embolism. JAMA 1986; 256: 744–49. ten Cate JW Prins MH. Major orthopaedic surgery and post-discharge DVT. Lancet 1996; 348: 209–10. Bergqvist D, Benoni G, Bjôrgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696–700.
SIR—Planes and colleagues1 and ten Cate and Prins (July 27, p 209)2 draw further attention to the unresolved and controversial issues of the occurrence of post-discharge venous thromboembolism in patients undergoing orthopaedic surgery and of the optimum duration of pharmacological prophylaxis. In patients discharged with a negative venogram a high frequency of venographyconfirmed DVT was recorded 3 weeks after discharge.1 Enoxaparin continued after discharge was effective in reducing the rate of DVT. At 3-month follow-up the rate of clinically overt thromboembolic events was 0·58%. We do not know whether thrombi detected by venography 35 days after surgery, but not causing symptoms, are clinically important. In fact, follow-up studies, including one from our group,3 showed a low rate of clinically overt thromboembolic events in patients discharged with negative venography. We carried out a literature review of the frequency of post-discharge clinically overt venous thromboembolism after orthopaedic surgery. We examined the studies published from January, 1974, to December, 1995, on the prophylaxis of venous thromboembolism after major orthopaedic surgery fulfilling the following criteria: (1) pharmacological prophylaxis restricted to the hospital stay; (2) bilateral venography before discharge; and (3) postdischarge follow-up of the patients for at least 4 weeks. Of 31 identified studies, 13 fulfilled the overview criteria. The total number of patients evaluated was 4120. An adequate venogram was obtained before discharge in 3469 patients (84%). In the 2361 patients with negative venography (68%), 30 episodes of symptomatic venous thromboembolism after hospital discharge were reported, with a resulting cumulative frequency of 1·27% (95% CI 0·82–1·72). Six of these 30 cases of DVT showed pulmonary embolism, which was fatal in one. The average
1180
2 3
4
Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348: 224–28. ten Cate JW, Prins MH. Major orthopaedic surgery and postdischarge DVT. Lancet 1996; 348: 209–10. Agnelli G, Ranucci V, Veschi F, Rinonapoli E, Lupattelli L, Nenci CG. Clinical outcome of hip surgery patients with negative lower limb venography at discharge. Thromb Haemost 1995; 74: 1042–44. Agnelli G, Radicchia S, Nenci CG. The diagnosis of deep vein thrombosis in asymptomatic high risk patients. Haemostasis 1995; 25: 40–48.
Varicoceles in young soccer players SIR—Varicocele is common in adolescence, though reports of its prevalence are conflicting.1,2 The aetiology is still largely unknown. Varicocele usually causes no symptoms, and is usually detected on routine physical examination of healthy children. We looked for varicocele in 198 healthy boys aged 10–14 years who were schoolchildren or young elite soccer players. 30 were sedentary, 19 trained 1–3 hours/week, 58 trained 4–6 hours/week, 18 trained 7–9 hours/week, and 73 trained for more than 10 hours/week. Height, weight, and pubertal stage according to Tanner were evaluated. Physical examination for varicocele was done by one investigator (AS) by palpating the spermatic cords with the boy standing up before and during a Valsalva manoeuvre; testicular size was measured with an orchidometer. The overall prevalence of varicocele (all left-sided) was 17·7% (35/198): 21/198 grade I (10·6%), 11/198 grade II (5·5%), and 3/198 grade III (1·5%). Prevalence of varicocele by degree of sports training is shown in the table. No difference was observed for age, height, weight, and pubertal stage. In the group who exercised more than 10 hours/week (the only group for which statistical analysis is reliable) the patients with varicocele showed a significant difference in testicular volume (right: 7·42 [SD 2·9] vs left: 6·72 [2·70] mL, p=0·01), while patients without varicocele did not (right: 8·97 [4·70] vs 8·81 [4·64] mL). We are unaware of any similar reports. Sports training might cause varicocele by some mechanical effects of exercise. Because varicocele can cause subfertility3 and prognosis for fertility will deteriorate if the varicocele persists,4 our findings suggest that a careful examination be
Vol 348 • October 26, 1996
THE LANCET
Sports training (hours/wk)
Number
Age (years mean [SD])
Height (cm mean [SD])
Weight (kg, mean [SD])
Pubertal stage
Varicocele all n (%)
Grade I n (%)
Grade II n (%)
Grade III n (%)
0 1–3 4–6 7–9 肁10
30 19 58 18 73
12·2 (1·0) 12·3 (1·2) 12·4 (1·0) 12·3 (1·0) 12·5 (0·9)
155 (7) 157 (5) 157 (6) 156 (8) 159 (8)
47 (9) 45 (5) 46 (4) 46 (3) 45 (5)
1–5 1–5 1–5 1–5 1–5
0 (0) 2 (10·5) 8 (13·8) 4 (22·2) 21 (28·8)
0 (0) 1 (5·2) 5 (8·6) 2 (11·1) 13 (17·8)
0 (0) 1 (5·3) 3 (5·1) 2 (11·1) 6 (8·2)
0 (0) 0 (0) 0 (0) 0 (0) 3 (4·1)*
*The 3 subjects with grade III underwent varicocele correction.
Table: Prevalence of varicocele in the 198 healthy adolescents
done of all adolescent athletes to detect and correct early,2 this important risk factor for future fertility. We thank the pupils of C Angelini Junior High School at Pavia and young soccer players of Milan AC, AC Pro Sesto, AC Monza, and AC Pavia; and G Levizzanmi (Milan AC), B Costantino (AC Pro Sesto), and L Besana (AC Monza) for their collaboration.
*Andrea Scaramuzza, Rodolfo Tavana, Antonietta Marchi Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Pavia; *Division of Pediatrics, Azienda Istituti Ospitalieri, I-26100 Cremona; and Medical Staff of Milan AC, Milan, Italy
1
2 3 4
Belloli G, D’Agostino S, Pesce C, Fantuz E. Adolescent varicocele and other testicular anomalies: an epidemiologic study. Med Surg Ped 1993; 15: 159–62. Kass EJ, Reitelman C. Adolescent varicocele. Urol Clin North Am 1995; 22: 151–59. Goldstein M. Adolescent varicocele. J Urol 1995; 153: 484–85. Hienz HA, Voggenthaler J, Weissbach L. Histological findings in testes with varicocele during childhood and their therapeutic consequences. Eur J Pediatr 1980; 133:139–46.
Resurgence of Vibrio cholerae O139 Bengal with altered antibiogram in Calcutta, India SIR—1992 saw the emergence in southern India of a novel serogroup currently classified as Vibrio cholerae O139 Bengal. On the basis of this microorganism’s ability to spread rapidly through cholera endemic areas in India and in neighbouring countries and on the propensity of the new serogroup to replace the O1 El Tor biotype, V cholerae O139 was described as the new pandemic strain of cholera.1 Surprisingly, however, in the subsequent years the El Tor biotype reappeared in most parts of the Indian subcontinent, replaced O139, and again became the dominant serogroup causing cholera (table).2 The reappearance of El Tor and the decline in O139 in the Indian subcontinent led investigators to believe that the emergence of O139 serogroup had been a one-time event. Continuing surveillance on V cholerae in Calcutta now reveals the resurgence of O139 since August, 1996. As of Sept 20, 1996, the monthly isolation rate of V cholerae O139 (59·7%) has exceeded that of O1 serogroup (30·6%) for the first time since November, 1993, in Calcutta (table). Of the 20 recent strains of V cholerae O139 examined, all were resistant to ampicillin and furazolidone; 95%, 85%, and 25% were resistant to neomycin, streptomycin, and tetracycline, respectively; and 10% of the strains were resistant to Year
1993 1994 1995 1996
Month(s)
Jan–June July–Dec Jan–June July–Dec Jan–June July–Dec Jan–June July Aug Sept
No (%) of V cholerae isolated O1
O139
Non-O1, non-O139
0 23 (9·9) 126 (69·2) 169 (77·5) 137 (84·9) 168 (71·2) 114 (72·6) 37 (72·5) 37 (62·7) 19 (30·6)
246 (94·9) 197 (84·9) 35 (19·2) 32 (14·7) 10 (6·1) 52 (22·0) 2 (1·3) 1 (1·9) 16 (27·1) 37 (59·7)
13 (5·1) 12 (5·2) 21 (11·6) 17 (7·8) 16 (9·8) 16 (6·8) 41 (26·1) 13 (25·6) 6 (10·2) 6 (9·7)
Table: Isolation of various serogroups of V cholerae from patients admitted because of acute secretory diarrhoea to Infectious Diseases Hospital, Calcutta
Vol 348 • October 26, 1996
gentamicin and nalidixic acid. All strains tested were susceptible to chloramphenicol, ciprofloxacin, cotrimoxazole, and norfloxacin. All strains were also sensitive to the vibriostatic agent pteridine. Therefore, unlike the O139 strains which emerged in November, 1992, in Calcutta,3 the current O139 isolates are sensitive to cotrimoxazole and pteridine, and the antibiogram of the current O139 differs from that of O139 isolated in 1992–93. We tested recent strains of V cholerae O139 by polymerase chain amplification to determine the presence of ctxA (encoding the enzymatic subunit of cholera toxin), zot (zonula occludens toxin), ace (accessory cholera toxin), and tcpA (major structural subunit of toxin coregulated pili). All the O139 strains examined were positive for the 301 bp ctxA, 243 bp zot, and 284 bp ace amplicons and also for the 471 bp tcpA amplicon, indicating that the genes comprising the virulence cassette and the gene encoding for the surface organelles required for intestinal colonisation were intact. The resurgence of O139 seems not to be limited to Calcutta since we have recently received O139 strains from Madras. The current resurgence could be a prelude to what happened in 1992 and efforts must again be initiated to monitor and control the spread of O139 at a global level. Rupak Mitra, Arnab Basu, D Dutta, *G Balakrish Nair, Yoshifumi Takeda *National Institute of Cholera and Enteric Diseases, Beliaghata, Calcutta-700 010, India; and Research Institute, International Medical Center of Japan, Tokyo
1 2
3
Nair GB, Ramamurthy T, Bhattacharya SK, et al. Spread of Vibrio cholerae O139 Bengal in India. J Infect Dis 1994; 169: 1029–34. Mukhopadhyay AK, Garg S, Mitra R, et al. Temporal shifts in traits of Vibrio cholerae strains isolated from hospitalized patients in Calcutta: a 3-year (1993 to 1995) analysis. J Clin Microbiol 1996; 34: 2537–43. Ramamurthy T, Garg S, Sharma R, et al. Emergence of novel strain of Vibrio cholerae with epidemic potential in southern and eastern India. Lancet 1993; 341: 703–04.
Long-term tacrine treatment in Alzheimer’s disease SIR—Solomon and colleagues (July 27, p 275)1 conclude that long-term tacrine could produce a continued symptomatic benefit for patients with Alzheimer’s disease remaining in treatment for almost 2 years. Their figure shows that after an initial improvement on the cognitive portion of the Alzheimer’s disease assessment scale (ADAS-Cog) of 2·6 points in tacrine-treated patients (5–9 months of therapy), a sustained decline that parallels the control group was seen for 11–15 and 17–21 months of treatment. We disagree that the initial delay of disease progression demonstrates a sustained efficacy beyond 5–9 months. In fact, the possible benefits of tacrine therapy on ADAS-Cog disappeared despite its continuous administration for several months. The study has also serious methodological drawbacks (small sample, non-randomised, non-blind drug administration and evaluation, possibly biased selection of controls) that could invalidate their findings. To support their results, they refer to published studies1–3 that unfortunately share some of these methodological problems. The results of Solomon and colleagues’ pilot study could be the basis for a hypothesis justifying the necessity of clinical
1181