Biomedical subjects
Publications and source records attributed to Z Cohen.
Hernias are common in patients with osteogenesis imperfecta, but to our knowledge there have been no reports of diaphragmatic hernias in such patients. We describe a patient with osteogenesis imperfecta in whom a diaphragmatic hernia contained a strangulated segment of the splenic flexure of the colon. Resection of the necrotic tissue and transverse colostomy resulted in an uneventful recovery.
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The usefulness of isolated intestinal pouches of an intestinal allograft for monitoring mucosal histology during rejection episodes was studied in a canine model. Total small intestinal autotransplantation was performed in four dogs, and allotransplantation in 18 dogs. Isolated pouches from the proximal and distal ends of the allografts were brought to the skin as stomas. Serial biopsies were obtained from these pouches. Nine allotransplants were treated with a suboptimal dose of cyclosporine. Nine allografted dogs were not immunosuppressed. Biopsies from all animals were normal the first two days postoperatively, and remained so in the autotransplants. Mononuclear cell infiltration in the lamina propria and submucosa was seen up to five days before death from rejection of the allograft in dogs on cyclosporine. At autopsy, all dogs had histologic findings in the transplanted bowel similar to those of simultaneously obtained pouch biopsies. The results show that histologic changes in isolated pouches from intestinal allotransplants reflect changes in the incontinuity segment of the graft and, therefore, such pouches can be used for histologic monitoring of the graft.
The management of malignant colonic polyps removed colonoscopically has been a controversial subject. A continuing series is reported of 36 patients with 37 malignant polyps removed by colonoscopic polypectomy (CP) between 1976 and 1982. Fourteen polyps contained carcinoma in situ (CIS); 13 were treated by CP alone; one was treated by CP and colectomy. Nineteen polyps contained invasive carcinoma; 13 were treated by CP alone; six were treated by CP and colectomy. Four patients had sessile polyps resected piecemeal, in which accurate staging was impossible. Two were treated with CP alone, and two had CP plus colectomy. All patients were followed with yearly colonoscopy and/or barium enema. Follow-up has been six to 84 months (mean 36 months). Twenty-seven patients whose polyps were treated by CP alone have had no evidence of recurrent tumor at the polypectomy site. Of the nine patients undergoing colectomy, six had residual tumor at the polypectomy resection site. No patients had involved lymph nodes. Our current approach to this problem is based on the degree of invasion and the status of the resection margins. Polyps containing CIS can safely be treated with CP alone. Polyps with invasive carcinoma and clear resection margins should be treated with CP and either colectomy or frequent repeat colonoscopy. This decision is a clinical one and must involve input from both the clinician and the pathologist. Those polyps whose resection margins are involved or where piecemeal excision precludes accurate pathologic assessment should undergo colectomy.
Absorption of cyclosporine and uptake of radiolabelled glucose by the transplanted small intestine in the dog was investigated to develop physiologic markers of rejection. Cyclosporine in olive oil was given orally, and glucose-14C was instilled into an isolated pouch constructed from the transplanted jejunum. Biopsies were simultaneously obtained from an isolated pouch made from the transplanted ileum. The absorption data were correlated with the histologic findings. Absorption of cyclosporine was of the same magnitude in autotransplanted dogs as it was in allotransplanted dogs with a normal graft. Absorption of cyclosporine in allotransplanted dogs with histologic signs of rejection was significantly reduced. Peak uptake of glucose-14C was noted 5 to 10 minutes after instillation of the isotope in autotransplanted and allotransplanted dogs with a normal graft. Allotransplanted dogs undergoing rejection had a delayed appearance of peak uptake and significantly reduced absolute uptake. In conclusion, absorption of cyclosporine and uptake of radiolabelled glucose can be utilized as functional monitors of intestinal allograft rejection.
In order to define the alteration of the function of the adrenergic system in hypertension, we studied directly the receptor-cyclase coupling protein (N protein), which is one of the components of the enzyme adenylate cyclase. N protein was determined in erythrocyte membranes of patients with essential hypertension and normal subjects, with a complementation assay in vitro. Fifteen normal subjects and 18 patients with essential hypertension (eight untreated and ten treated with beta-adrenoreceptor blocking drugs alone or in combination with other antihypertensive drugs), and two patients with pseudohypoparathyroidism type Ia (known to have deficient N protein activity), were studied. Erythrocyte N protein activities in the various groups expressed as percentages of the means +/- SD of normals were: normal subjects 100 + 13.7, untreated hypertensive 108.9 +/- 20.4, treated hypertensive 104.3 +/- 11.3 and pseudohypoparathyroidism type Ia 43%. The difference between N protein activity in the hypertensive patients and normals was not statistically significant. We suggest that the molecular basis for the altered sympathetic responsiveness in essential hypertension may reside in other components of the cyclic AMP protein kinase effector system.
Hormone sensitive adenylate cyclase consists of at least three components; hormone receptor, a catalytic unit, and the N-protein, which couples the receptor to the catalytic unit. Human erythrocytes have very low adenylate cyclase activity, but do have N-protein activity. We have investigated the fate of the catalytic unit and the N protein during maturation of human reticulocytes. We compared red blood cell membranes derived from nine patients with reticulocytosis averaging 12% to erythrocyte membranes from eight normal subjects. The catalytic unit was assayed by stimulation of adenylate cyclase with forskolin, and the N-protein activity by an in vitro complementation assay. Forskolin stimulated adenylate cyclase activity was ten times higher in membranes derived from patients with reticulocytosis as compared with those of normal subjects. N-protein activity was only slightly (12%) and insignificantly (P = 0.08) higher in the reticulocytosis patients membranes. We conclude that during maturation of the human erythrocyte there is a differential loss of the catalytic unit of adenylate cyclase.
Arteriovenous shunts were constructed in 12 dogs for simplified venous access. A modified end-in-end technique was used. In this technique, the donor vessel is telescoped into the recipient vessel and kept in place with two sutures, not exposed to the blood stream. Mean skin-to-skin time was 17 minutes. Ten shunts were patent one week after construction. Nine were open after one month. We have concluded that this anastomotic technique is suitable for the construction of arteriovenous shunts in dogs and that it facilitates venous access.
Most procedures for diverting urine sacrifice continence, but Kock's modification of the ileal conduit promises the ideal of appliance-free urine storage with voluntary control of emptying. The authors report on two men who underwent this procedure. One was a paraplegic who had total urinary incontinence after a sphincterotomy. The other had a carcinoma of the rectosigmoid obstructing the right ureter. He had congenital bladder exstrophy and had undergone ureteric implantation into the sigmoid colon at 3 years of age. In both patients, the reservoir was created from an isolated 60-cm segment of the middle portion of small bowel. Two nipple valves were created - one to prevent reflux and one to provide continence of urine. Follow-up was 27 and 17 months respectively. One patient had his outlet valve revised because of sliding and incontinence. He is now completely continent of urine and he intubates his reservoir three to four times daily. Postoperatively, the second patient had a leak at the ureteroileal anastomosis, but this healed spontaneously. The continent urinary diversion is a major intestinal operation and should not be performed in conjunction with exenteration. It should be confined to a few centres where greater experience can be accumulated.
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A report is given on 26 patients (18 men and 8 women) undergoing low anterior resection for carcinoma of the rectum, using both the TA 55 and EEA staplers. The average age was 65 years (range, 45 to 92 years). The preoperative level of the lesion from the anal verge averaged 9.8 cm (range, 4 to 17 cm). All had well-differentiated or moderately well-differentiated lesions. All lesions were removed using the following technique. The TA 55 stapler was placed across the lower rectum at the distal resection margin. The EEA stapler was introduced into the rectum with the anvil removed. The shaft was then passed through the rectum stump either through or immediately adjacent to the staple line. The anvil was refitted and the anastomosis completed between the more proximal colon and the rectal stump. A defunctioning colostomy was employed in only one patient. There has been no mortality. Follow-up has been 2 to 16 months, and there has been no early recurrence. The postoperative level of the anastomosis averaged 5.5 cm (range, 2 to 11 cm). Stapler-related complications occurred in three patients. One of these patients developed a postoperative anastomotic leak, which necessitated a defunctioning colostomy. Two anastomotic strictures occurred following either an anastomotic leak or postoperative radiation therapy. Early incontinence to gas, night-time anal soilage, and urgency occurred in eight patients (30 per cent). These symptoms improved or disappeared within three months following operation. The authors' preliminary experience has shown the double stapling technique to have definite advantages. It obviates the use of lower purse-string suture and permits a lower and easier anastomosis. It avoids the problem of disparity of sizes of the two ends of the bowel. The rectum is not opened and fecal spillage is minimized. To date, results have been good without excessive complications.
The effect of the new immunosuppressant cyclosporine on survival after total small intestinal allotransplantation (TSIA) was studied in a canine model. Successful TSIA was performed in 34 dogs. Eleven dogs were treated with cyclosporine, 25 mg/kg/day i.m., starting the day before the operation and continuing for four weeks. Thereafter the same dose was given orally. Thirteen dogs were given oral cyclosporine only, 25 mg/kg/day from the day after transplantation. Ten dogs served as controls. The dogs treated with intramuscular and oral cyclosporine survived a mean of 103.8 +/- 39.4 days (mean +/- S.E.M.). The longest survivor died after 432 days. Survival in this group was significantly longer than that of the control dogs, which survived 12.5 +/- 4.6 days. The orally treated dogs survived 30.4 +/- 7.6 days. All control dogs, and seven of the orally treated dogs, but only two of the intramuscularly treated dogs, died of acute rejection. It is concluded that cyclosporine is effective in prolonging survival after TSIA in the dog and reduces the incidence of acute rejection.
Management of the perineal wound following rectal excision was assessed in 57 patients at the Toronto General Hospital; 40 had ulcerative colitis, 4 had Crohn's disease, 10 had carcinoma of the rectum, 2 had carcinoma of the anus and 1 had anal incontinence. The preferred technique was careful anatomical dissection with meticulous hemostasis, and primary skin closure with a laterally placed closed Hemovac suction system. Alternatively, wounds were packed and allowed to heal secondarily. Overall, the perineal wound healed primarily in 41 patients (72%). Primary closure was possible in 50 patients (88%); in 41 (82%) the wound healed without complication but in 9 (18%) the wound had to be opened because of hematoma and abscess (8 patients) or bleeding (1 patient). In 41 (91%) of the 44 patients with inflammatory bowel disease the perineal wound was closed primarily; 34 wounds (83%) healed without complication. In seven patients the perineal wound was packed at surgery because of bleeding (four), fecal spillage (two) or sepsis (one). Healing time averaged 6 months. These results indicate that primary closure is the optimal management of perineal wounds. Primary healing is achieved in a high proportion of patients and postoperative morbidity is decreased. Results are excellent in patients with inflammatory bowel disease as well as in those with carcinoma.
Perforation of a Meckel's diverticulum by a sharp object often presents with subtle nonspecific abdominal findings. A 53-year-old man had features resembling acute appendicitis and right ureteral obstruction. At laparotomy a wooden toothpick was found perforating a Meckel's diverticulum. The diagnosis of complicated Meckel's diverticulum should be considered when there is typical right lower quadrant pain or the patient is known to have ingested a sharp foreign body. The mortality resulting from perforation is low. The authors discuss other complications of Meckel's diverticulum.
In conclusion, it is the intention of our Familial Polyposis Registry to ensure that members of an affected family are aware of the reasons for ongoing surveillance and of the potential for developing extracolonic manifestations or malignancies. A second and equally important aim is to make available to the medical community-at-large reliable and progressive resource data, not only to stimulate discussion about the total management of familial polyposis, but to encourage cooperation in our common goal of cancer prevention.
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A continent reservoir ileostomy was constructed in 85 patients, 9 of whom were adolescents. Indications for the procedure included organic problems related to the ileostomy as well as psychologic and sexual difficulties related to an external appliance. Fifty-eight patients had conversion from a conventional ileostomy. Twenty-five patients underwent total proctocolectomy and Kock ileostomy. An intussuscepted "nipple valve" was used in all cases. Follow-up ranged from 4 to 10 months. There were no operative deaths. Eighty-two patients are completely continent with regard to both flatus and stool. Only two patients wear an external appliance. No one has requested a return to a conventional ileostomy. No reservoirs have been removed. Ten of the initial 17 patients (59%) required at least one additional surgical procedure for early or late complications, the most frequent of which were intestinal obstruction, sliding or prolapse of the nipple valve and fistula. Technical modifications have reduced this morbidity; they included using SGIA staples across the nipple valve and a fascial sling around the outlet. These modifications have been used in 28 additional patients and in 5 from the original series. Ten of these 33 patients (30%) have required intra-abdominal operation for revision, 5 because of sliding of the nipple valve. Further modifications using a Marlex mesh sling have been made in 40 additional patients and in 7 patients from the original series. Six of these 47 patients (11%) have undergone or will undergo intra-abdominal operation for revision. Only one case of nipple valve sliding has occurred in this group. Marlex mesh has now been replaced by Prolene mesh. The benefits of the continent ileostomy are substantial. The author's results have continued to improve with experience and with the technical modifications outlined.
The continent Koch ileostomy constitutes a major improvement in the quality of life for patients requiring an ileostomy. Complete continence is achieved in most patients, although the mechanisms underlying this control of fecal flow are poorly understood. Pressure studies on the pouch, the nipple valve and the outlet were preformed and results showed the presence of a high pressure zone in the nipple valve relative to the pouch. The high pressure zone maintained, even when the intra-abdominal pressure was raised or during contractions of the pouch, and most likely, contributes to continence. The pressure in the nipple valve and outlet was further intermittently increased by spontaneously occurring phasic and tonic contractions. Distention of the pouch with air caused a tonic contraction that was first recorded from the pouch and that traveled aborally along the intestinal layers of the intususcepted nipple valve and the outlet. By frequent emptying of the pouch, such contractions are avoided, and the risk of desusception of the nipple valve may be reduced.