315
clinical
We advise caution in treatment with because of the possibility of severe neurological
improvement.8
gangliosides toxicity.
N. Y. received a fellowship from the Japan Society for the promotion of Science for Japanese Junior Scientists. Supported in part by grants-in-aid from the Ministry of Education, Science, and Culture of Japan and the Ministry of Health and Welfare of Japan. We thank Dr Toru Nakao and Dr Yoshio Hirabayashi (Department of Biochemistry, Faculty of Pharmaceutical Science, University of Shizuoka) for valuable advice. Department of Neurology, Brain Research Institute,
Niigata Univeristy, Niigata, 951 Japan
NOBUHIRO YUKI SHUZO SATO TADASHI MIYATAKE
Department of Internal Medicine, Yamagata University
KAZUHIKO SUGIYAMA TADASHI KATAGIRI HIDEO SASAKI
Third
Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for GuillainBarré syndrome. Ann Neurol 1990; 27 (suppl): 21-24. 2. Latov N, Hays AP, Donofrio PD, et al. Monoclonal IgM with a unique specificity to gangliosides GM1 and GD1b and to lacto-N-tetraose associated with human motor neuron disease. Neurology 1988; 38: 763-68. 3. Pestronk A, Comblath DR, Ilyas AA, et al. A treatable multifocal neuropathy with 1.
antibodies to GM1ganglioside. Ann Neurol 1988; 24: 73-78.
Shy ME, Heimann-Patterson T, Parry GJ, Tahmoush AJ, Evans VA, Schick PK. Lower motor neuron disease in a patient with autoantibodies against Gal(&bgr;1-3) GalNAc in gangliosides GM1 and GD1b: improvement following immunotherapy. Neurology 1990; 40: 842-44. 5. Nobile-Orazio E, Carpo M, Legname G, Meucci N, Sonnino S, Scarlato G. Anti-GM1 IgM antibodies in motor neuron disease and neuropathy. Neurology 1990; 40: 4.
1747-50. 6. Ilyas AA, Li S-C, Chou DKH,
et al. Gangliosides GM2, IV4GalNAcGM1b, and IV4GalNAcGD1a as antigens for monoclonal immunoglobulin M in neuropathy
associated with gammopathy. J Biol Chem 1988; 263: 4369-73. N, Sato S, Takashi I, Miyatake T, Yoshino H. Axonal degeneration in the Guillain-Barre syndrome an anti-GM1 ganglioside antibodies. Muscle Nerve (in
7. Yuki
8.
press). Bradley WG. Critical review of gangliosides and thyrotropin-releasing hormone in peripheral neuromuscular diseases. Muscle Nerve 1990; 13: 833-42.
Pouch-vaginal fistulae after ileoanal anastomoses
SIR,-Mr Markham and colleagues (May 25, p 1295) report successful repair of pouch-vaginal fistula by Martius’ method. Fistula after ileoanal anastomosis is a serious complication and often leads to the need for pouch excision. Fistulae may form from the pouch or ileoanal anastomosis to the anterior abdominal wall, urinary tract, vulva, or vagina. There have been sporadic reports of such fistulae, and of their repair.1-4 These reports included only eight patients. Six others have been recorded,s-7 but because of this limited experience, there is no definitive treatment for pouchvaginal fistulae. Some treatment options such as re-establishment of diverting ileostomy, simple closure, sliding flap advancement techniques, curettage, and fistulotomy have been proposed. Sepsis is thought frequently to cause fistula by spontaneous drainage of pelvic sepsis or abscess anteriorly through the rectovaginal septum. A reduction in the rate of pelvic sepsis might reduce the frequency of pouch-related fistula formation. Galandiuk et al8 have shown a decrease in pelvic sepsis rate with increased experience of the technique; they also noted that the decrease in pelvic sepsis might be attributable to the use of a shorter rectal cuff. However, we had two out of five cases of pouch-vaginal fistula in a minimum cuff group (ie, muscle cuff 2 cm above the dentate line) and none in forty-one in the medium cuff group (5-7 cm above the dentate line).9 We believe that it is better to preserve an adequate muscle cuff not only with respect to functional outcome but also for structural reinforcement of the vagina. We also found very low anal resting and squeeze pressure in patients with pouch-vaginal fistula. One of our patients underwent gracilis muscle repair, but this failed. She finally had a permanent ileostomy. The other had fistulectomy and repair was successful. However, she had no high-pressure zone in her anal canal. Repeated surgical treatment of fistula may result in fibrosis and incontinence, especially in patients with ulcerative colitis. The average time of pouch excision following ileoanal anastomosis after various salvage procedures was more than 47 months after
operation.8 What was the functional outcome after Markham and colleagues’ procedure? Doctors who use ileoanal anastomosis are interested in the fate of patients with pouch-vaginal fistula. MASATO KUSUNOKI
Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663, Japan Second
SHINSUKE FUJITA YASUTSUGU SHOJI YOUICHIROU SAKANOUE JOJI UTSUNOMIYA
1. Cohen
Z, McLeod RS, Stem H, et al. The pelvic pouch and ileoanal anastomosis procedure; surgical technique and initial results. Am J Surg 1985; 150: 601-07. 2. Fonkalsrud EW. Update on clinical experience with different surgical techniques of the endorectal pull-through operation for colitis and polyposis. Surg Gynecol Obstet 1987; 165: 309-16. 3. Schoetz DJ Jr, Coller JA, Veidenheimer MC. Can the pouch be saved? Dis Col Rect 1988; 31: 671-75. 4. Keighley MRB, Yoshioka K, Kmiot W. Prospective randomized trial to compare the stapled double lumen pouch for restorative proctocolectomy. Br J Surg 1988; 75: 1008-11. 5. Everett WG. Experience of restorative proctocolectomy with ileal reservoir. Br J Surg 1989; 76: 77-81. 6. Vasilevsky CA, Rothenberger DA, Goldberg SM. The S ileal pouch-anal anastomosis. World J Surg 1987; 11: 742-50. 7. Williams NS, Narzouk DEMM, Hallan RI, et al. Function after ileal pouch and stapled pouch-anal anastomosis for ulcerative colitis. Br J Surg 1989; 76: 1168-71. 8. Galandiuk S, Scott NA, Dozois RR, et al. Ileal pouch-anal anastomosis: reoperation for pouch-related complications Ann Surg 1990; 212: 446-54. 9. Shoji Y, Kusunoki M, Fujita S, et al. Functional role of the preserved rectal cuff in ileoanal anastomosis. Surgery (in press).
The
case
against thiomersal
StR,—Thiomersal is a weak antibacterial agent that is rapidly broken down to products, including ethylmercury residues, which are neurotoxic. Its role as a preservative in vaccines has been questioned,1 and the pharmaceutical industry itself considers its use as "historical". Cell-mediated immunity (CMI) has been reported and we have been looking at the frequency of CMI to thiomersal (and phenol) by intradermal testing with concentrations similar to those used in ophthalmic and topical preparations. With their informed consent we investigated 116 patients with chronic blepharitis (mean age 48) and 8 healthy people without blepharitis (mean age 34). 28 patients (24%) had a history of atopy, which compares with the 30% prevalence rate for a normal population. No patient or healthy volunteer wore contact lenses. Thiomersal was given by intradermal injection in the left forearm as 0-1 ml isotonic saline containing 0-005% thiomersal (5 ug), the concentration used in eyedrops. This was kept in a darkened bottle at 4°C, and was changed weekly. Phenol was given by intradermal injection in the right forearm as 0 1 ml isotonic saline preserved with 0-5% phenol. Injection sites were examined at 15 min for any wheal-and-flare reaction and at 48 hours for swelling and induration. Systemic side-effects were investigated by observation and direct questioning of the patients. With thiomersal no patient showed an early wheal-and-flare response. 7 (6%) of patients but none of the 8 healthy volunteers responded with a CMI response. CMI was noted in 3 of 28 atopic patients and in 4 of the 88 non-atopics (not significant). Induration reactions averaged 7-3 mm (SD 3-7). No systemic side-effects or late sequelae were identified. With the phenol/saline there were no early responses or late indurations; and no side-effects were reported. This group of patients with chronic blepharitis had also been tested for CMI to staphylococcal antigens and 40% were found to express CMI to Staphylococcus aureus protein A,2 Of the 7 patients with CMI to thiomersal, 3 also expressed CMI to S aureus antigens, which is the expected frequency in blepharitis. This suggests that these patients were not generally hyperimmune. Others have investigated CMI by patch-testing; Hansson and Moller3reported the highest rate (18% in those of average age 20, reducing to 7% at a mean 45). Is this CMI response to thiomersal important enough to preclude use of this preservative in vaccines, contact lens solutions, and eye and nose drops? Delayed hypersensitivity to thiomersal was described in 1981 in people who used contact lens care solutions preserved with thiomersal.4 Patients experienced conjunctival hyperaemia, punctate epithelial keratopathy, and increasing intolerance to lens wear. CMI was confirmed by patch testing. Discontinuation of the
clinical
We advise caution in treatment with because of the possibility of severe neurological
improvement.8
gangliosides toxicity.
N. Y. received a fellowship from the Japan Society for the promotion of Science for Japanese Junior Scientists. Supported in part by grants-in-aid from the Ministry of Education, Science, and Culture of Japan and the Ministry of Health and Welfare of Japan. We thank Dr Toru Nakao and Dr Yoshio Hirabayashi (Department of Biochemistry, Faculty of Pharmaceutical Science, University of Shizuoka) for valuable advice. Department of Neurology, Brain Research Institute,
Niigata Univeristy, Niigata, 951 Japan
NOBUHIRO YUKI SHUZO SATO TADASHI MIYATAKE
Department of Internal Medicine, Yamagata University
KAZUHIKO SUGIYAMA TADASHI KATAGIRI HIDEO SASAKI
Third
Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for GuillainBarré syndrome. Ann Neurol 1990; 27 (suppl): 21-24. 2. Latov N, Hays AP, Donofrio PD, et al. Monoclonal IgM with a unique specificity to gangliosides GM1 and GD1b and to lacto-N-tetraose associated with human motor neuron disease. Neurology 1988; 38: 763-68. 3. Pestronk A, Comblath DR, Ilyas AA, et al. A treatable multifocal neuropathy with 1.
antibodies to GM1ganglioside. Ann Neurol 1988; 24: 73-78.
Shy ME, Heimann-Patterson T, Parry GJ, Tahmoush AJ, Evans VA, Schick PK. Lower motor neuron disease in a patient with autoantibodies against Gal(&bgr;1-3) GalNAc in gangliosides GM1 and GD1b: improvement following immunotherapy. Neurology 1990; 40: 842-44. 5. Nobile-Orazio E, Carpo M, Legname G, Meucci N, Sonnino S, Scarlato G. Anti-GM1 IgM antibodies in motor neuron disease and neuropathy. Neurology 1990; 40: 4.
1747-50. 6. Ilyas AA, Li S-C, Chou DKH,
et al. Gangliosides GM2, IV4GalNAcGM1b, and IV4GalNAcGD1a as antigens for monoclonal immunoglobulin M in neuropathy
associated with gammopathy. J Biol Chem 1988; 263: 4369-73. N, Sato S, Takashi I, Miyatake T, Yoshino H. Axonal degeneration in the Guillain-Barre syndrome an anti-GM1 ganglioside antibodies. Muscle Nerve (in
7. Yuki
8.
press). Bradley WG. Critical review of gangliosides and thyrotropin-releasing hormone in peripheral neuromuscular diseases. Muscle Nerve 1990; 13: 833-42.
Pouch-vaginal fistulae after ileoanal anastomoses
SIR,-Mr Markham and colleagues (May 25, p 1295) report successful repair of pouch-vaginal fistula by Martius’ method. Fistula after ileoanal anastomosis is a serious complication and often leads to the need for pouch excision. Fistulae may form from the pouch or ileoanal anastomosis to the anterior abdominal wall, urinary tract, vulva, or vagina. There have been sporadic reports of such fistulae, and of their repair.1-4 These reports included only eight patients. Six others have been recorded,s-7 but because of this limited experience, there is no definitive treatment for pouchvaginal fistulae. Some treatment options such as re-establishment of diverting ileostomy, simple closure, sliding flap advancement techniques, curettage, and fistulotomy have been proposed. Sepsis is thought frequently to cause fistula by spontaneous drainage of pelvic sepsis or abscess anteriorly through the rectovaginal septum. A reduction in the rate of pelvic sepsis might reduce the frequency of pouch-related fistula formation. Galandiuk et al8 have shown a decrease in pelvic sepsis rate with increased experience of the technique; they also noted that the decrease in pelvic sepsis might be attributable to the use of a shorter rectal cuff. However, we had two out of five cases of pouch-vaginal fistula in a minimum cuff group (ie, muscle cuff 2 cm above the dentate line) and none in forty-one in the medium cuff group (5-7 cm above the dentate line).9 We believe that it is better to preserve an adequate muscle cuff not only with respect to functional outcome but also for structural reinforcement of the vagina. We also found very low anal resting and squeeze pressure in patients with pouch-vaginal fistula. One of our patients underwent gracilis muscle repair, but this failed. She finally had a permanent ileostomy. The other had fistulectomy and repair was successful. However, she had no high-pressure zone in her anal canal. Repeated surgical treatment of fistula may result in fibrosis and incontinence, especially in patients with ulcerative colitis. The average time of pouch excision following ileoanal anastomosis after various salvage procedures was more than 47 months after
operation.8 What was the functional outcome after Markham and colleagues’ procedure? Doctors who use ileoanal anastomosis are interested in the fate of patients with pouch-vaginal fistula. MASATO KUSUNOKI
Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663, Japan Second
SHINSUKE FUJITA YASUTSUGU SHOJI YOUICHIROU SAKANOUE JOJI UTSUNOMIYA
1. Cohen
Z, McLeod RS, Stem H, et al. The pelvic pouch and ileoanal anastomosis procedure; surgical technique and initial results. Am J Surg 1985; 150: 601-07. 2. Fonkalsrud EW. Update on clinical experience with different surgical techniques of the endorectal pull-through operation for colitis and polyposis. Surg Gynecol Obstet 1987; 165: 309-16. 3. Schoetz DJ Jr, Coller JA, Veidenheimer MC. Can the pouch be saved? Dis Col Rect 1988; 31: 671-75. 4. Keighley MRB, Yoshioka K, Kmiot W. Prospective randomized trial to compare the stapled double lumen pouch for restorative proctocolectomy. Br J Surg 1988; 75: 1008-11. 5. Everett WG. Experience of restorative proctocolectomy with ileal reservoir. Br J Surg 1989; 76: 77-81. 6. Vasilevsky CA, Rothenberger DA, Goldberg SM. The S ileal pouch-anal anastomosis. World J Surg 1987; 11: 742-50. 7. Williams NS, Narzouk DEMM, Hallan RI, et al. Function after ileal pouch and stapled pouch-anal anastomosis for ulcerative colitis. Br J Surg 1989; 76: 1168-71. 8. Galandiuk S, Scott NA, Dozois RR, et al. Ileal pouch-anal anastomosis: reoperation for pouch-related complications Ann Surg 1990; 212: 446-54. 9. Shoji Y, Kusunoki M, Fujita S, et al. Functional role of the preserved rectal cuff in ileoanal anastomosis. Surgery (in press).
The
case
against thiomersal
StR,—Thiomersal is a weak antibacterial agent that is rapidly broken down to products, including ethylmercury residues, which are neurotoxic. Its role as a preservative in vaccines has been questioned,1 and the pharmaceutical industry itself considers its use as "historical". Cell-mediated immunity (CMI) has been reported and we have been looking at the frequency of CMI to thiomersal (and phenol) by intradermal testing with concentrations similar to those used in ophthalmic and topical preparations. With their informed consent we investigated 116 patients with chronic blepharitis (mean age 48) and 8 healthy people without blepharitis (mean age 34). 28 patients (24%) had a history of atopy, which compares with the 30% prevalence rate for a normal population. No patient or healthy volunteer wore contact lenses. Thiomersal was given by intradermal injection in the left forearm as 0-1 ml isotonic saline containing 0-005% thiomersal (5 ug), the concentration used in eyedrops. This was kept in a darkened bottle at 4°C, and was changed weekly. Phenol was given by intradermal injection in the right forearm as 0 1 ml isotonic saline preserved with 0-5% phenol. Injection sites were examined at 15 min for any wheal-and-flare reaction and at 48 hours for swelling and induration. Systemic side-effects were investigated by observation and direct questioning of the patients. With thiomersal no patient showed an early wheal-and-flare response. 7 (6%) of patients but none of the 8 healthy volunteers responded with a CMI response. CMI was noted in 3 of 28 atopic patients and in 4 of the 88 non-atopics (not significant). Induration reactions averaged 7-3 mm (SD 3-7). No systemic side-effects or late sequelae were identified. With the phenol/saline there were no early responses or late indurations; and no side-effects were reported. This group of patients with chronic blepharitis had also been tested for CMI to staphylococcal antigens and 40% were found to express CMI to Staphylococcus aureus protein A,2 Of the 7 patients with CMI to thiomersal, 3 also expressed CMI to S aureus antigens, which is the expected frequency in blepharitis. This suggests that these patients were not generally hyperimmune. Others have investigated CMI by patch-testing; Hansson and Moller3reported the highest rate (18% in those of average age 20, reducing to 7% at a mean 45). Is this CMI response to thiomersal important enough to preclude use of this preservative in vaccines, contact lens solutions, and eye and nose drops? Delayed hypersensitivity to thiomersal was described in 1981 in people who used contact lens care solutions preserved with thiomersal.4 Patients experienced conjunctival hyperaemia, punctate epithelial keratopathy, and increasing intolerance to lens wear. CMI was confirmed by patch testing. Discontinuation of the
