685
Hyperosmolar glucose solution or prostaglandin-F2&agr; for ectopic pregnancy SIR,-Dr Lang and colleagues (July 14, p 78) report conservative ectopic pregnancy with local injection of hyperosmolar or prostaglandin- F2. They raise certain points that solution glucose treatment of
and clarification. methotrexate or prostaglandins "... even if state that al Lang administered locally, have systemic effects, some of which can be severe". With respect to the local administration of methotrexate in the treatment of tubal ectopic pregnancy, on what data did Lang et al base this statement? In published reports of the intra-amniotic injection of methotrexate’-3 and our own study of 18 patients treated with laparoscopic local injection of methotrexate (unpublished), there seem to be no adverse side-effects. Lang and colleagues also state "a urinary hCG level of 500 IU/1 or under ... [was] required for an attempt at primary conservative management". However, within tablei (clinical data for 15 patients treated with prostaglandin), and table 11 (clinical data for 16 patients treated with glucose), there are 4 and 3 patients, respectively, with urinary hCG levels above this value.
warrant comment et
It is noteworthy that the serum &bgr;-sub-unit hCGs in both arms of the study, with the exception of 3 patients, were all below 1000 mIU/ml. Fernandez et al4 showed that an initial p-hCG concentration of less than 1000 mIU/ml was associated with a high probability of spontaneous resolution of the pregnancy. In fact, if one removes the results of those patients who did not fit the inclusion criteria (ie, a urinary hCG of 500 IU/ml or less), then all the serum hCG values are below 1000 mIU/ml. My final comment concerns the implication that hyperosmolar glucose is not cytotoxic, whereas methotrexate is. Hyperosmolar glucose will in fact have been non-discriminatory in its actions on the cells and possibly affect the cells of the tubal mucosa as well as the trophoblast. Lang and colleagues’ points about their concern over the possible residual ovarian levels of local methotrexate are well taken, but I feel one should be cautious lest the indiscriminate use of what seems to be a "benign" solution, such as hyperosmolar glucose, produces tubal damage. Carson House, 121 Railway Road, Subiaco, WA 6008, Australia
Lancet 1987; i: 381. 2. Leeton J, Davison G. Nonsurgical management of unruptured tubal pregnancy with intra-amniotic methotrexate preliminary report of two cases Fertil Steril 1988; 50: 167-69. 3 Kojima E, Abe Y, Morita M, Ito M, Hirakawa S, Momose K. The treatment of unruptured tubal pregnancy with intratubal methotrexate injection under laparoscopic control. Obstet Gynecol 1990; 75: 723. 4 Fernandez H, Rainborn JD, Papiernik E, Bellet D, Frydman R. Spontaneous resolution of ectopic pregnancy. Obstet Gynecol 1982; 60: 13-14.
*** This letter has been shown to Dr Lang and his colleagues, whose reply follows.-ED. L. SIR,-Our patients had a urinary hCG level of 5000 IU/1 or less, and not, as wrongly stated in the text and as correctly shown in our earlier Lancet publication,l of 500 IU/1 or less. We have so far successfully treated 38 patients with tubal pregnancies and serum hCG concentrations of 2500 mIU/ml or less with instillation of a 50% glucose solution. We do not know how much our patients may benefit from local instillation of a 50% glucose solution. Expectant management with a serum hCG level of 2500 mIU/ml or less has proved to be associated with a failure rate of 7-18% .2-4
Thompson correctly
notes
have been reported after local
that
no
treatment
systemic complications with methotrexate (in
prostaglandins, to which we referred in our statement "even if administered locally"). But methotrexate is a cytotoxic agent and systemic effects via the tubal vessels cannot be ruled out, even after local application. In addition, systemic side-effects such
contrast to
Department of Obstetrics and Gynaecology, University of Graz, A-8036 Graz, Austria
PETER F. LANG W. HÖNIGL
1 Lang P, Weiss PAM, Mayer HO. Local application of hyperosmolar glucose solution in tubal pregnancy. Lancet 1989; ii: 922-23 2. Garcia AJ, Aubert JM, Jama J, Josimovich JB. Expectant management of presumed ectopic pregnancies. Fertil Steril 1987; 48: 395-400. 3. Fernandez H, Rainkorn JD, Papiemik E, Bellet D, Frydman R. Spontaneous resolution of ectopic pregnancy. Obstet Gynecol 1988; 71: 171-74. 4. Sauer MV, Anderson RE, Vermesh M, et al. Spontaneously resorbing ectopic pregnancy: preservation of human chorionic gonadotropin bioactivity despite declining steroid hormone levels. Am J Obstet Gynecol 1989; 161: 1673-76. 5. Ory SJ, Villaneuva AL, Sand PK, Tamura RK. Conservative treatment of ectopic pregnancy with methotrexate. Am J Obstet Gynecol 1986, 154: 1299-306 6. Feichtinger W, Kemeter P. Conservative treatment of ectopic pregnancy by transvaginal aspiration under sonographic control and methotrexate injection. Lancet 1987; i: 381. 7. Kojima E, Abe Y, Morita M, Sto M, Hirakawa S, Momose K. The treatment of unruptured tubal pregnancy with intratubal methotrexate infection under laparoscopic control. Obstet Gynecol 1990; 75: 723-25. 8. Pansky M, Bukovsky J, Golan A, et al. Local methotrexate injection: a nonsurgical treatment of ectopic pregnancy. Am J Obstet Gynecol 1989; 161: 313-16.
resulting from &agr;1-adrenoceptor blockade
Faecal incontinence
SiR,—The use of adrenoceptor-blocking drugs for treatment of benign prostatic hyperplasia is increasing as alternatives to surgery are sought. Transuretheral surgery has potential side-effects, including possible long-term cardiovascular effects.! Relaxation of smooth muscle within the prostatic urethra by al-adrenoceptor blockers such as prazosin can reduce bladder outlet obstruction, as shown urodynamically and symptomatically.2 On the basis of
G. R. THOMPSON
1. Feichtinger W, Kemeter P. Conservative treatment of ectopic pregnancy by transvaginal aspiration under sonographic control and methotrexate injection.
Dr
increase in serum concentrations of liver enzymes5 have not been looked for in previous investigations. Hyperosmolar glucose is intended to induce local necrobiosis. We believe damage to the tubal wall is unlikely and those of our patients who underwent second-look laparoscopy after 3-6 months showed no lasting tubal damage. Nevertheless, the ability of the tube to regenerate is shown by reports of intrauterine pregnancy after bipolar coagulation of the tubes for sterilisation. as an
a
urine flow of 114
mllmin
and cystoscopy
a
diagnosed as having bladder outflow obstruction due to benign hyperplasia. He was prescribed prazosin 2 mg twice daily. This brought relief of his urinary symptoms, but 2 weeks after starting prazosin he noticed faecal incontinence, initially during exercise. 4 months after starting on prazosin he had a Milligan-Morgan haemorrhoidectomy, which exacerbated the 52-year-old
man
was
faecal incontinence such that he became incontinent to both intestinal gas and solid stool. On examination there was voluntary contraction of the anal sphincter but a diminished resting anal tone. This persisted for 3 weeks but ceased almost immediately on discontinuation of prazosin. The anal sphincter mechanism comprises an internal smooth muscle element and an external striated component. The presence of a and p adrenoceptors in the smooth muscle has been known for some time but their role in the maintenance of faecal continence has been controversial. The presence and significance of sympathetic excitatory adrenergic innervation has recently been recognised. Normal internal sphincter tone is thought to be partly maintained by noradrenaline, an important neurotransmitter in sympathetic nerves supplying the internal anal sphincter;4 the external sphincter has no such component. It is the striated muscle which can be damaged during haemorrhoidectomy, so that minor faecal incontinence results.55 We propose that the faecal incontinence with prazosin was due to relaxation of the smooth muscle element of the sphincter by al-adrenoceptor blockade. This was exacerbated by haemorrhoidectomy. The return of normal continence following haemorrhoidectomy was then prohibited by the loss of internal sphincter tone. Incontinence persisted until discontinuation of prazosin, which supports the suggestion that the sympathetic nervous system has a role in the maintenance of anal tone, in a way similar to that in the bladder neck. Urologists need to be aware of
686
this potential side-effect before starting o-adrenoreceptor blockade in patients with anal sphincter mechanisms compromised for other reasons.
Department of Urology and General St Bartholomew’s Hospital, London EC1 4BE, UK
Surgery,
S. A. V. HOLMES T. J. CHRISTMAS J. J. WOOD R. S. KIRBY
NP, Wennberg JE, Malenka DJ, et al. Mortality and reoperation after transuretheral resection of the prostate for benign prostatic hyperplasia. N Engl J Med 1989; 320: 1120-24. 2. Chapple CR, Christmas TJ, Milory EJG. A twelve week placebo controlled study of prazosin in the treatment of prostatic obstruction. Urol Int 1990; 45: 47-55. 3. Parks AG, Fishlock DJ, Cameron JDH, et al. Preliminary investigation of the pharmacology of the human internal anal sphincter. Gut 1969; 10: 647-77. 4. Speakman CTM, Hoyle CHV, Kamm MA, et al. Adrenergic control in the internal anal sphincter is abnormal in patients with idiopathic faecal incontinence. Br J Surg 1. Roos
1990; 77: 669. 5. Thomson WHF. The nature of haemorrhoids.
Br J Surg 1975; 62: 542-52.
Spongiform encephalopathy in an Israeli born to immigrants from Libya SIR,-The means of transmission of kuru, Creutzfeldt-Jakob disease (CJD), and Gerstmann-Straussler syndrome (GSS) remains controversial. While kuru in the Pacific has been eliminated,z a high frequency of CJD persists among Jewish immigrants from Libya. 3,4 We describe a patient with this syndrome who was born in Israel to parents of Libyan origin. A 37-year-old man was admitted to our department because of bilateral intention tremor which had developed over the preceding month and prevented him from working. On examination, there was no evidence of cognitive impairment. There was ocular dysmetria and ataxic speech, frequent myoclonic jerks in the upper limbs, action myoclonus, and ataxia of the limbs. Muscle tone was somewhat rigid with contralateral activation. Tendon reflexes were brisk and the gait was ataxic and wide-based. Cerebellar ataxia increased and eventually the patient, while still completely conscious, was confined to bed, unable to speak or swallow. The myoclonic jerks became so intense that the patient injured himself on the bed rails. Clonazepam (6 mg daily) suppressed these abnormal movements. Rigidity and dystonic postures of the limbs developed, and 8 weeks after admission he lapsed into coma. Repeated electroencephalograms were normal for 6 weeks. Then typical semi-periodic 1/s discharges of sharp and slow waves appeared and persisted. Routine blood tests, an HIV test, and ferroxidase were normal, as was cerebrospinal fluid. Computed tomography and magnetic resonance imaging were normal initially, although 4 weeks later the tomogram showed mild cerebral atrophy. The patient died 14 weeks after admission. Necropsy showed spongiform changes and widespread gliosis in the brain. The patient’s parents emigrated from Libya to Israel about 3 years before his birth. They were non-consanguineous, and no other family member is known to have CJD. It is noteworthy that neither the patient nor other members of the family ever consumed brain. The patient also reported that he never ate eyeballs. The high frequency of CJD among Jewish immigrants to Israel from Libya has been noted,3,4 but its cause is unclear. It has been speculated that the disease is transmitted to humans by consumption of sheep brain infected with scrapie.3,M! There are no data on the frequency of scrapie in Libya or on the prevalence of CJD among non-Jews in Libya. The circumstances of the present case mean that a new hypothesis for the pathogenesis of the disease among Libyan Jews is required. Although our patient had no family member known to be affected, the high frequency of positive family history for the disease, particularly among parents or siblings, in other cases of Libyan origin has been noted.4 Thus, the possibility of genetic transmission is suggested. Even though genetic transmission occurs in 6-15% of CJD patients,9,10 it is commonly thought to characterise GSS. Our patient, and others of Libyan origin in Israel, had a cerebellar presentation at the onset
of disease, which is also typical of GSS. Although CJD and GSS are considered to be separate diseases, the distinction in individual cases may be difficult. For example, a family combining clinical and pathological features of CJD and GSS has been described,9 and "CJD virus" has been isolated from GSS patients." The prion protein gene is located on the short arm of human chromosome 20, and seems to be abnormal in both diseases.12,13 Presently, we are involved in a genetic study of Libyan Jewish patients to try and verify whether a mutation of the gene coding PrPZ7-30 is responsible for the high frequency of the disease among these
patient. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
PUIU NISIPEANU BARUCH EL AD AMOS D. KORCZYN
1. Beck E, Daniel PM. Neuropathology of transmissible spongiform encephalopathies. In: Prusiner SB, McKinley MP, eds. Pnons: novel infectious pathogens causing scrapie and Creutzfeldt-Jakob disease. San Diego: Academic Press, 1987:331-83 2. Klitzman RL, Alpers MP, Gajdusek DC. The natural incubation period of Kuru and the episodes of transmission in three clusters of patients. Neuroepidemiology 1985; 3: 3-20. 3. Kahana E, Alter M, Braham J, Safer D. Creutzfeldt-Jakob disease: focus among Libyan Jews in Israel Science 1974; 183: 90-91 4. Neugut RH, Neugut AI, Kahane E, Stem Z, Alter M. Creutzfeldt-Jakob disease: familial clustering among Libyan born Israelis. Neurology 1979; 29: 225-31. 5. Herzberg L, Herzberg B, Gibbs CJ, et al Creutzfeldt-Jakob disease, hypothesis for high incidence in Libyan Jews in Israel. Science 1974; 186: 848 6. Alter M, Frank Y, Doyne H, Webster DH. Creutzfeldt-Jakob disease after eating ovine brains? N Engl JMed 1975; 292: 927. 7. Davinpour Z, Alter M, Sobel E, Ascher DM, Gajdusek DC. A case control study of Creutzfeldt-Jakob disease. Dietary risk factors. Am J Epidemiol 1985; 122: 443-51. 8. Baron H, Cathala F, Brown P, Chatelain J, Gajdusek DC. Familial Creutzfeldt-Jakob disease in France: epidemiological implications. Eur J Epidemiol 1986; 2: 252-64 9. Masters CL, Harris EO, Gajdusek DC, et al. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 1979; 5: 177-88. 10. Masters CL, Gajdusek DC, Gibbs CJ. Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Straussler syndrome. Brain 1981; 104: 559-88. 11. Westaway D, Carlson GA, Prusiner SB. Unravelling prion diseases through molecular genetics. Trends Neurol Sci 1989; 12: 221-27. 12. Collinge J, Harding AE, Owen F, et al. Diagnosis of Gerstmann-Straussler syndrome in familiar dementia with prion protein gene analysis. Lancet 1989; ii: 15-17 13. Hsiao K, Baler HF, Crow TJ, et al. Linkage of a prion protein missense vanant to Gerstmann-Straussler syndrome. Nature 1989; 338: 342-45.
Polymerase chain reaction decontamination: the wipe test SIR,-False-positives are a major difficulty of the polymerase chain (PCR).1-3 In our experience, even the most rigorous precautions can be inadequate when contaminating DNA persists in the environment. We propose that a wipe test, like that used to monitor radioactive contamination, is useful for decontaminating the PCR laboratory. Our laboratory uses PCR for the detection of herpes simplex virus and human herpesvirus 6 (HHV-6). In the past few months false-positive controls have begun to plague our HHV-6 results. Despite a clean-up effort that involved moving the PCR area to a separate room; replacing reagents; wearing gowns, mob caps, bootees, masks,’ and gloves; and decontaminating all equipment, we still had a false-positive rate ranging from 10-100%. The source of contamination could not be attributed to specific reagents. Also, the contaminating DNA reacted only with some primer pairs, suggesting that the source was probably PCR products rather than
reaction
HHV-6 genomes.
Wipe tests were done to find the sources of contamination. We tested 70 laboratory sites by wiping each suspect surface with a fresh swab (’Dacroswab’ Type 1, Spectrum Laboratories, Los Angeles) moistened in deionised water. Each swab was rinsed in 0’ 1 ml water, and 5 )1 of the resulting solution was amplified with primer sets derived from HHV-6. Representative results are shown in the upper part of the figure: 4 of 5 negative controls and 6 of 8 wipe test sites had varying levels of positivity. While some of these data may reflect the problematic false-positive rate obtained with this primer set, certain sites (eg, freezer door handle, freezer shelf, room door
Hyperosmolar glucose solution or prostaglandin-F2&agr; for ectopic pregnancy SIR,-Dr Lang and colleagues (July 14, p 78) report conservative ectopic pregnancy with local injection of hyperosmolar or prostaglandin- F2. They raise certain points that solution glucose treatment of
and clarification. methotrexate or prostaglandins "... even if state that al Lang administered locally, have systemic effects, some of which can be severe". With respect to the local administration of methotrexate in the treatment of tubal ectopic pregnancy, on what data did Lang et al base this statement? In published reports of the intra-amniotic injection of methotrexate’-3 and our own study of 18 patients treated with laparoscopic local injection of methotrexate (unpublished), there seem to be no adverse side-effects. Lang and colleagues also state "a urinary hCG level of 500 IU/1 or under ... [was] required for an attempt at primary conservative management". However, within tablei (clinical data for 15 patients treated with prostaglandin), and table 11 (clinical data for 16 patients treated with glucose), there are 4 and 3 patients, respectively, with urinary hCG levels above this value.
warrant comment et
It is noteworthy that the serum &bgr;-sub-unit hCGs in both arms of the study, with the exception of 3 patients, were all below 1000 mIU/ml. Fernandez et al4 showed that an initial p-hCG concentration of less than 1000 mIU/ml was associated with a high probability of spontaneous resolution of the pregnancy. In fact, if one removes the results of those patients who did not fit the inclusion criteria (ie, a urinary hCG of 500 IU/ml or less), then all the serum hCG values are below 1000 mIU/ml. My final comment concerns the implication that hyperosmolar glucose is not cytotoxic, whereas methotrexate is. Hyperosmolar glucose will in fact have been non-discriminatory in its actions on the cells and possibly affect the cells of the tubal mucosa as well as the trophoblast. Lang and colleagues’ points about their concern over the possible residual ovarian levels of local methotrexate are well taken, but I feel one should be cautious lest the indiscriminate use of what seems to be a "benign" solution, such as hyperosmolar glucose, produces tubal damage. Carson House, 121 Railway Road, Subiaco, WA 6008, Australia
Lancet 1987; i: 381. 2. Leeton J, Davison G. Nonsurgical management of unruptured tubal pregnancy with intra-amniotic methotrexate preliminary report of two cases Fertil Steril 1988; 50: 167-69. 3 Kojima E, Abe Y, Morita M, Ito M, Hirakawa S, Momose K. The treatment of unruptured tubal pregnancy with intratubal methotrexate injection under laparoscopic control. Obstet Gynecol 1990; 75: 723. 4 Fernandez H, Rainborn JD, Papiernik E, Bellet D, Frydman R. Spontaneous resolution of ectopic pregnancy. Obstet Gynecol 1982; 60: 13-14.
*** This letter has been shown to Dr Lang and his colleagues, whose reply follows.-ED. L. SIR,-Our patients had a urinary hCG level of 5000 IU/1 or less, and not, as wrongly stated in the text and as correctly shown in our earlier Lancet publication,l of 500 IU/1 or less. We have so far successfully treated 38 patients with tubal pregnancies and serum hCG concentrations of 2500 mIU/ml or less with instillation of a 50% glucose solution. We do not know how much our patients may benefit from local instillation of a 50% glucose solution. Expectant management with a serum hCG level of 2500 mIU/ml or less has proved to be associated with a failure rate of 7-18% .2-4
Thompson correctly
notes
have been reported after local
that
no
treatment
systemic complications with methotrexate (in
prostaglandins, to which we referred in our statement "even if administered locally"). But methotrexate is a cytotoxic agent and systemic effects via the tubal vessels cannot be ruled out, even after local application. In addition, systemic side-effects such
contrast to
Department of Obstetrics and Gynaecology, University of Graz, A-8036 Graz, Austria
PETER F. LANG W. HÖNIGL
1 Lang P, Weiss PAM, Mayer HO. Local application of hyperosmolar glucose solution in tubal pregnancy. Lancet 1989; ii: 922-23 2. Garcia AJ, Aubert JM, Jama J, Josimovich JB. Expectant management of presumed ectopic pregnancies. Fertil Steril 1987; 48: 395-400. 3. Fernandez H, Rainkorn JD, Papiemik E, Bellet D, Frydman R. Spontaneous resolution of ectopic pregnancy. Obstet Gynecol 1988; 71: 171-74. 4. Sauer MV, Anderson RE, Vermesh M, et al. Spontaneously resorbing ectopic pregnancy: preservation of human chorionic gonadotropin bioactivity despite declining steroid hormone levels. Am J Obstet Gynecol 1989; 161: 1673-76. 5. Ory SJ, Villaneuva AL, Sand PK, Tamura RK. Conservative treatment of ectopic pregnancy with methotrexate. Am J Obstet Gynecol 1986, 154: 1299-306 6. Feichtinger W, Kemeter P. Conservative treatment of ectopic pregnancy by transvaginal aspiration under sonographic control and methotrexate injection. Lancet 1987; i: 381. 7. Kojima E, Abe Y, Morita M, Sto M, Hirakawa S, Momose K. The treatment of unruptured tubal pregnancy with intratubal methotrexate infection under laparoscopic control. Obstet Gynecol 1990; 75: 723-25. 8. Pansky M, Bukovsky J, Golan A, et al. Local methotrexate injection: a nonsurgical treatment of ectopic pregnancy. Am J Obstet Gynecol 1989; 161: 313-16.
resulting from &agr;1-adrenoceptor blockade
Faecal incontinence
SiR,—The use of adrenoceptor-blocking drugs for treatment of benign prostatic hyperplasia is increasing as alternatives to surgery are sought. Transuretheral surgery has potential side-effects, including possible long-term cardiovascular effects.! Relaxation of smooth muscle within the prostatic urethra by al-adrenoceptor blockers such as prazosin can reduce bladder outlet obstruction, as shown urodynamically and symptomatically.2 On the basis of
G. R. THOMPSON
1. Feichtinger W, Kemeter P. Conservative treatment of ectopic pregnancy by transvaginal aspiration under sonographic control and methotrexate injection.
Dr
increase in serum concentrations of liver enzymes5 have not been looked for in previous investigations. Hyperosmolar glucose is intended to induce local necrobiosis. We believe damage to the tubal wall is unlikely and those of our patients who underwent second-look laparoscopy after 3-6 months showed no lasting tubal damage. Nevertheless, the ability of the tube to regenerate is shown by reports of intrauterine pregnancy after bipolar coagulation of the tubes for sterilisation. as an
a
urine flow of 114
mllmin
and cystoscopy
a
diagnosed as having bladder outflow obstruction due to benign hyperplasia. He was prescribed prazosin 2 mg twice daily. This brought relief of his urinary symptoms, but 2 weeks after starting prazosin he noticed faecal incontinence, initially during exercise. 4 months after starting on prazosin he had a Milligan-Morgan haemorrhoidectomy, which exacerbated the 52-year-old
man
was
faecal incontinence such that he became incontinent to both intestinal gas and solid stool. On examination there was voluntary contraction of the anal sphincter but a diminished resting anal tone. This persisted for 3 weeks but ceased almost immediately on discontinuation of prazosin. The anal sphincter mechanism comprises an internal smooth muscle element and an external striated component. The presence of a and p adrenoceptors in the smooth muscle has been known for some time but their role in the maintenance of faecal continence has been controversial. The presence and significance of sympathetic excitatory adrenergic innervation has recently been recognised. Normal internal sphincter tone is thought to be partly maintained by noradrenaline, an important neurotransmitter in sympathetic nerves supplying the internal anal sphincter;4 the external sphincter has no such component. It is the striated muscle which can be damaged during haemorrhoidectomy, so that minor faecal incontinence results.55 We propose that the faecal incontinence with prazosin was due to relaxation of the smooth muscle element of the sphincter by al-adrenoceptor blockade. This was exacerbated by haemorrhoidectomy. The return of normal continence following haemorrhoidectomy was then prohibited by the loss of internal sphincter tone. Incontinence persisted until discontinuation of prazosin, which supports the suggestion that the sympathetic nervous system has a role in the maintenance of anal tone, in a way similar to that in the bladder neck. Urologists need to be aware of
686
this potential side-effect before starting o-adrenoreceptor blockade in patients with anal sphincter mechanisms compromised for other reasons.
Department of Urology and General St Bartholomew’s Hospital, London EC1 4BE, UK
Surgery,
S. A. V. HOLMES T. J. CHRISTMAS J. J. WOOD R. S. KIRBY
NP, Wennberg JE, Malenka DJ, et al. Mortality and reoperation after transuretheral resection of the prostate for benign prostatic hyperplasia. N Engl J Med 1989; 320: 1120-24. 2. Chapple CR, Christmas TJ, Milory EJG. A twelve week placebo controlled study of prazosin in the treatment of prostatic obstruction. Urol Int 1990; 45: 47-55. 3. Parks AG, Fishlock DJ, Cameron JDH, et al. Preliminary investigation of the pharmacology of the human internal anal sphincter. Gut 1969; 10: 647-77. 4. Speakman CTM, Hoyle CHV, Kamm MA, et al. Adrenergic control in the internal anal sphincter is abnormal in patients with idiopathic faecal incontinence. Br J Surg 1. Roos
1990; 77: 669. 5. Thomson WHF. The nature of haemorrhoids.
Br J Surg 1975; 62: 542-52.
Spongiform encephalopathy in an Israeli born to immigrants from Libya SIR,-The means of transmission of kuru, Creutzfeldt-Jakob disease (CJD), and Gerstmann-Straussler syndrome (GSS) remains controversial. While kuru in the Pacific has been eliminated,z a high frequency of CJD persists among Jewish immigrants from Libya. 3,4 We describe a patient with this syndrome who was born in Israel to parents of Libyan origin. A 37-year-old man was admitted to our department because of bilateral intention tremor which had developed over the preceding month and prevented him from working. On examination, there was no evidence of cognitive impairment. There was ocular dysmetria and ataxic speech, frequent myoclonic jerks in the upper limbs, action myoclonus, and ataxia of the limbs. Muscle tone was somewhat rigid with contralateral activation. Tendon reflexes were brisk and the gait was ataxic and wide-based. Cerebellar ataxia increased and eventually the patient, while still completely conscious, was confined to bed, unable to speak or swallow. The myoclonic jerks became so intense that the patient injured himself on the bed rails. Clonazepam (6 mg daily) suppressed these abnormal movements. Rigidity and dystonic postures of the limbs developed, and 8 weeks after admission he lapsed into coma. Repeated electroencephalograms were normal for 6 weeks. Then typical semi-periodic 1/s discharges of sharp and slow waves appeared and persisted. Routine blood tests, an HIV test, and ferroxidase were normal, as was cerebrospinal fluid. Computed tomography and magnetic resonance imaging were normal initially, although 4 weeks later the tomogram showed mild cerebral atrophy. The patient died 14 weeks after admission. Necropsy showed spongiform changes and widespread gliosis in the brain. The patient’s parents emigrated from Libya to Israel about 3 years before his birth. They were non-consanguineous, and no other family member is known to have CJD. It is noteworthy that neither the patient nor other members of the family ever consumed brain. The patient also reported that he never ate eyeballs. The high frequency of CJD among Jewish immigrants to Israel from Libya has been noted,3,4 but its cause is unclear. It has been speculated that the disease is transmitted to humans by consumption of sheep brain infected with scrapie.3,M! There are no data on the frequency of scrapie in Libya or on the prevalence of CJD among non-Jews in Libya. The circumstances of the present case mean that a new hypothesis for the pathogenesis of the disease among Libyan Jews is required. Although our patient had no family member known to be affected, the high frequency of positive family history for the disease, particularly among parents or siblings, in other cases of Libyan origin has been noted.4 Thus, the possibility of genetic transmission is suggested. Even though genetic transmission occurs in 6-15% of CJD patients,9,10 it is commonly thought to characterise GSS. Our patient, and others of Libyan origin in Israel, had a cerebellar presentation at the onset
of disease, which is also typical of GSS. Although CJD and GSS are considered to be separate diseases, the distinction in individual cases may be difficult. For example, a family combining clinical and pathological features of CJD and GSS has been described,9 and "CJD virus" has been isolated from GSS patients." The prion protein gene is located on the short arm of human chromosome 20, and seems to be abnormal in both diseases.12,13 Presently, we are involved in a genetic study of Libyan Jewish patients to try and verify whether a mutation of the gene coding PrPZ7-30 is responsible for the high frequency of the disease among these
patient. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
PUIU NISIPEANU BARUCH EL AD AMOS D. KORCZYN
1. Beck E, Daniel PM. Neuropathology of transmissible spongiform encephalopathies. In: Prusiner SB, McKinley MP, eds. Pnons: novel infectious pathogens causing scrapie and Creutzfeldt-Jakob disease. San Diego: Academic Press, 1987:331-83 2. Klitzman RL, Alpers MP, Gajdusek DC. The natural incubation period of Kuru and the episodes of transmission in three clusters of patients. Neuroepidemiology 1985; 3: 3-20. 3. Kahana E, Alter M, Braham J, Safer D. Creutzfeldt-Jakob disease: focus among Libyan Jews in Israel Science 1974; 183: 90-91 4. Neugut RH, Neugut AI, Kahane E, Stem Z, Alter M. Creutzfeldt-Jakob disease: familial clustering among Libyan born Israelis. Neurology 1979; 29: 225-31. 5. Herzberg L, Herzberg B, Gibbs CJ, et al Creutzfeldt-Jakob disease, hypothesis for high incidence in Libyan Jews in Israel. Science 1974; 186: 848 6. Alter M, Frank Y, Doyne H, Webster DH. Creutzfeldt-Jakob disease after eating ovine brains? N Engl JMed 1975; 292: 927. 7. Davinpour Z, Alter M, Sobel E, Ascher DM, Gajdusek DC. A case control study of Creutzfeldt-Jakob disease. Dietary risk factors. Am J Epidemiol 1985; 122: 443-51. 8. Baron H, Cathala F, Brown P, Chatelain J, Gajdusek DC. Familial Creutzfeldt-Jakob disease in France: epidemiological implications. Eur J Epidemiol 1986; 2: 252-64 9. Masters CL, Harris EO, Gajdusek DC, et al. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 1979; 5: 177-88. 10. Masters CL, Gajdusek DC, Gibbs CJ. Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Straussler syndrome. Brain 1981; 104: 559-88. 11. Westaway D, Carlson GA, Prusiner SB. Unravelling prion diseases through molecular genetics. Trends Neurol Sci 1989; 12: 221-27. 12. Collinge J, Harding AE, Owen F, et al. Diagnosis of Gerstmann-Straussler syndrome in familiar dementia with prion protein gene analysis. Lancet 1989; ii: 15-17 13. Hsiao K, Baler HF, Crow TJ, et al. Linkage of a prion protein missense vanant to Gerstmann-Straussler syndrome. Nature 1989; 338: 342-45.
Polymerase chain reaction decontamination: the wipe test SIR,-False-positives are a major difficulty of the polymerase chain (PCR).1-3 In our experience, even the most rigorous precautions can be inadequate when contaminating DNA persists in the environment. We propose that a wipe test, like that used to monitor radioactive contamination, is useful for decontaminating the PCR laboratory. Our laboratory uses PCR for the detection of herpes simplex virus and human herpesvirus 6 (HHV-6). In the past few months false-positive controls have begun to plague our HHV-6 results. Despite a clean-up effort that involved moving the PCR area to a separate room; replacing reagents; wearing gowns, mob caps, bootees, masks,’ and gloves; and decontaminating all equipment, we still had a false-positive rate ranging from 10-100%. The source of contamination could not be attributed to specific reagents. Also, the contaminating DNA reacted only with some primer pairs, suggesting that the source was probably PCR products rather than
reaction
HHV-6 genomes.
Wipe tests were done to find the sources of contamination. We tested 70 laboratory sites by wiping each suspect surface with a fresh swab (’Dacroswab’ Type 1, Spectrum Laboratories, Los Angeles) moistened in deionised water. Each swab was rinsed in 0’ 1 ml water, and 5 )1 of the resulting solution was amplified with primer sets derived from HHV-6. Representative results are shown in the upper part of the figure: 4 of 5 negative controls and 6 of 8 wipe test sites had varying levels of positivity. While some of these data may reflect the problematic false-positive rate obtained with this primer set, certain sites (eg, freezer door handle, freezer shelf, room door
