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Biomedical subjects

Z Cohen

Publications and source records attributed to Z Cohen.

At least 163 records · Page 9Linked to original sources

Surgical management of fulminant pseudomembranous colitis.

The presentation of pseudomembranous colitis ranges from mild self-limiting diarrhea to fulminant colitis with overwhelming sepsis. The management of the severe forms of this disease, including the role of surgical intervention, is poorly defined. To evaluate the management and outcome in severe cases, the authors reviewed the records of six patients (four women, two men) seen at The Toronto Hospital between 1985 and 1989 with pseudomembranous colitis manifesting as fulminant colitis. The patients ranged in age from 19 to 69 years (mean 52 years). All presented with nonbloody diarrhea, had peritoneal signs and were severely dehydrated, and all had received antibiotics between 4 days and 6 weeks before the onset of symptoms. The mean preoperative leukocyte count was 40.9 x 10(9)/L. Radiologically, the colon appeared to be dilated in three patients. Two patients were operated on immediately. The other four were treated medically, but three of them required surgery within 24 hours of presentation. Four (67%) of the six patients died. All four had been treated surgically. The mean age of the survivors was 28 years compared with 64 years for those who died. Pseudomembranous colitis can present as severe acute colitis and can carry a high mortality, especially in the aged. Surgical treatment may be required in those who fail to respond to medical management or have peritoneal signs.

Adult↗

Comparison of functional activity in host and graft mesenteric lymphoid tissue of rats receiving syngeneic heterotopic small bowel allografts with portal or systemic drainage.

With the accompanying paper these studies provide further evidence that functionally important lymphoid cell trafficking takes place in mesenteric tissue under the apparent control of factor(s) filtered by hepatic tissue. The role that these regulatory mechanisms have to play on survival of vascular allografts with venous drainage into either the portal or systemic circulation remains to be elucidated.

Animals↗

Altered cell trafficking in mesenteric lymphoid tissue following syngeneic heterotopic small bowel transplantation in rodents.

These data indicate that in rat heterotopic syngeneic SBT, the venous drainage system of the graft has profound effects on cell recovery in the gut-associated lymphoid tissue of both graft and host. Depending on the functional status of the same lymphoid tissue (Gorezynski, personal communication, 1992) one could thus anticipate significant perturbation of host-antigraft (and GVH) reactivity in allogeneic situations according to the venous drainage used. The mechanism(s) responsible for these effects have not been investigated. However, one testable hypothesis is that (a) factor(s) from the gut can control lymphoid recirculation within the mesenteric lymphoid tissue, and that this (these) factor(s) are absorbed under normal circumstances by hepatic tissue.

Animals↗

Pelvic pouch emptying scan: an evaluation of scintigraphic assessment of the neorectum.

Although scintigraphic pelvic pouch emptying scans have been used to evaluate neorectal function in patients who have undergone colectomy, mucosal proctectomy, and ileoanal pouch anastomosis, previous reports have not documented the reliability of this test in measuring pouch volume and emptying. Thus, this study was undertaken to determine: (1) the reliability of this test in patients with stable functional results and, (2) whether the emptying fraction correlates with the volume of the pouch. Ten patients who had stable functional results had 99m Tc-sulphur colloid pouch emptying scans performed on two occasions, one week apart. The average volume of artificial stool that was instilled was 338 +/- 104 cc. The mean difference in the volume instilled between the initial and repeat scans was 78 +/- 26 cc and the mean absolute difference in the percentage evacuated was 12 +/- 9 percent. These inter-test differences were not statistically significant (p greater than 0.05). There was no correlation between the volume of artificial stool instilled into the pelvic pouch and the fraction spontaneously emptied (r = -0.1). Our results suggest that the 99m Tc-sulphur colloid pelvic pouch emptying scan is reliable in patients with stable functional results. Pouch emptying fraction is independent of pouch volume.

Adult↗

Results of the pelvic-pouch procedure in patients with Crohn's disease.

The pelvic-pouch procedure has become a standard operation for selected patients with ulcerative colitis, but is contraindicated in patients with Crohn's disease at our institution. However, the distinction between ulcerative colitis and Crohn's colitis can sometimes be difficult, if not impossible. Between January 1982, and March 1989, 272 patients with ulcerative colitis underwent pelvic-pouch procedures at our institution. Nine (3.5 percent) of these patients eventually were found to have Crohn's disease. The records of these patients were examined to assess their clinical outcome and complication rate. There were five females and four males with a mean age of 28.8 years. In five patients (Group I) the diagnosis of Crohn's disease was made postoperatively on histologic examination of the rectum. The ileostomy was closed in all patients. Two developed complications necessitating excision of the pouch. Three patients are well. In the other four cases (Group II) the mean time to diagnosis was 2.5 years after the pouch procedure. Three patients developed pouch-vaginal fistula, and one multiple anal fissures and stenosis. Two required excision of the pouch whereas two have a functioning pouch but with a persistent pouch-vaginal fistula (n = 1) or anal fissures (n = 1). Overall, four patients have had their pouches removed, and five patients have functioning pouches: three with no complications and two with persistent perianal disease. Thus, we would conclude that the pelvic-pouch procedure should not knowingly be performed in patients with Crohn's disease because of the high associated complication rate.

Adolescent↗

Subtotal colectomy for ulcerative colitis: complications related to the rectal remnant.

Complications related to the retained rectal remnant were reviewed in 136 patients undergoing subtotal colectomy for acute ulcerative colitis. Fifty-five patients (Group 1) had a closed rectal stump brought up into the subcutaneous tissue, and 30 (Group 2) had an open mucous fistula. These were compared with an intrapelvic Hartmann's pouch performed in 51 patients (Group 3). All patients eventually had a pelvic pouch procedure. Age, duration and activity of disease, and preoperative steroid use were similar in all groups. There was no mortality. The rectal stump in 19 Group 1 patients (35 percent) spontaneously opened, and seven (13 percent) developed local left lower quadrant wound infections. Two Group 1 patients (4 percent) developed pelvic septic complications, as compared with two Group 2 patients (7 percent) and six Group 3 patients (12 percent). Subsequent pelvic dissection was difficult in 20 percent of Group 3 patients, vs. 4 percent and 0 percent of Group 1 and Group 2 patients, respectively (P less than 0.05). Persistent rectal disease activity was present in 41 percent of Group 3, vs. 27 percent of Groups 1 and 2. Our study suggests that exteriorization of the closed rectal stump following subtotal colectomy is associated with fewer pelvic septic complications and minimal local morbidity, facilitates subsequent pelvic dissection, and is not associated with increased disease activity in the retained rectum.

Abscess↗

Quality of life of patients with ulcerative colitis preoperatively and postoperatively.

Two instruments, the time trade-off technique and direct questioning of objectives, were used to assign the worth (utility) of the perceived quality of life of patients who had ulcerative colitis requiring surgery. Utilities ranged from 0 to 1 with 0 signifying death and 1 signifying full health. Two groups of patients were studied. Group 1 consisted of 20 patients (14 male and 6 female; mean age, 34.0 +/- 10.3 years) who were studied preoperatively and 1 year postoperatively. The mean preoperative utility was 0.58 +/- 0.34 using the time trade-off technique and 0.38 +/- 0.27 using the direct questioning of objectives. Mean utilities were significantly higher postoperatively, 0.98 +/- 0.07 using the time trade-off technique and 0.88 +/- 0.19 using the direct questioning of objectives (P less than 0.05). Group 2 included 93 patients who had had surgery at least 1 year previously. Twenty-eight had conventional ileostomies, 28 had Kock pouches, and 37 had ileal reservoirs. Mean utilities for these three subgroups ranged from 0.87 +/- 0.18 to 0.97 +/- 0.6. No significant differences were detected among the three subgroups. This study suggests that quality of life is improved after surgery for ulcerative colitis and is high irrespective of the surgical procedure.

Adult↗

Osteopenia, hematopoiesis, and bone remodelling in iliac crest and femoral biopsies: a prospective study of 102 cases of femoral neck fractures.

Cancellous microanatomy, bone remodelling, and hematopoietic tissue were studied in iliac crest and femoral neck biopsies taken intraoperatively in 102 consecutive patients with displaced intracapsular fractures. About half of the femoral biopsies had osteopenia, and most showed replacement of hematopoietic tissue by fat cells, with absence of osteoblasts and osteoclasts. In contrast, most of the iliac crest biopsies showed relatively less decrease in cancellous bone, while hematopoietic tissue and bone remodelling cells were present in approximately 75%. These results indicate that the iliac crest biopsy does not necessarily reflect cancellous microanatomy, hematopoietic tissue, and bone remodelling at other skeletal sites in any given patient.

Aged↗

Effect of colectomy on bile composition, cholesterol crystal formation, and gallstones in patients with ulcerative colitis.

Bile composition and the presence of cholesterol crystals in bile were studied in bile samples obtained at the time of surgery in patients with ulcerative colitis. Some patients were sampled before colectomy and others at a second operation months to years after a colectomy. Patients in the precolectomy group were found to have bile composition similar to control patients without gallstones, and few had crystals in their bile. In the postcolectomy group, cholesterol concentrations were very high, all biles were supersaturated, and almost all patients had cholesterol crystals in their bile. These findings are similar to those found in persons with cholesterol gallstones. Twenty patients have been followed for at least 3 years after colectomy and to date three have formed cholesterol gallstones.

Adult↗

The comparative effects of cyclosporin A and 16,16 dimethyl prostaglandin E2 on the allogeneic induction of monocyte/macrophage procoagulant activity and the cytokines macrophage procoagulant inducing factor and interleukin-2.

It has recently been reported that combination immunotherapy utilizing cyclosporin A (CsA) and prostaglandin E (PGE) reduced the frequency of acute renal allograft rejection; however, the mechanism for the benefit of this combination therapy is uncertain. Since our previous studies have suggested that macrophage procoagulant activity (PCA) is an important mediator of allograft rejection, in this study we have examined the effects of CsA and 16,16 dimethyl prostaglandin E2 (dmPGE2) alone and in combination on the induction of macrophage PCA and on the lymphokines macrophage procoagulant-inducing factor (MPIF) and interleukin-2 (IL-2) in vitro. Alloantigen-induced MPIF activity could be detected within 8 hr, reaching maximal levels by 12 hr and could still be detected at 24 hr. Allogeneic induction of PCA in splenic mononuclear cells was detectable by 24 hr, reaching maximal levels at 72 hr and was still detectable after 120 hr. CsA at concentrations from 100 ng/ml to 1000 ng/ml completely inhibited production of MPIF and IL-2, but had minimal effects on the ability of MPIF to induce isolated macrophage to express PCA. In contrast, dmPGE2 (10(-12)-10(-6) M) inhibited both the induction of MPIF and the ability of MPIF directly to induce macrophages to express PCA, with lesser effects on the induction of IL-2. The effects of minimal inhibitory concentrations of CsA and dmPGE2 in combination resulted in synergistic inhibition of PCA induction. These data demonstrate the disparate actions of CsA and dmPGE2 on inhibition of PCA, MPIF and IL-2, and provide a possible mechanism for the beneficial effects of combination CsA and dmPGE2 in patients receiving organ allografts.

16,16-Dimethylprostaglandin E2↗

Pulmonary plasma-cell granuloma.

A large pulmonary plasma-cell granuloma (PCG) mimicking a mediastinal germinal-cell tumor in a 9-year-old boy is presented. The nonspecificity of the tumoral calcifications and of the radiographic and CT findings in pulmonary PCG is demonstrated.

Calcinosis↗

Crohn's disease and pregnancy.

Seventy-eight pregnancies in 50 patients were reviewed to evaluate the effects of Crohn's disease on the outcome of pregnancy and the influence of the pregnancy on the course of Crohn's disease. Overall, 21 pregnancies (27 percent) had abnormal outcomes including spontaneous abortions (9), infants small for gestational age (6), premature infants (5), and infants who developed respiratory distress (1). Eight (50 percent) patients with active disease compared with 13 (21 percent) patients with inactive disease at conception had abnormal outcomes (P less than 0.05). During pregnancy 15 (55 percent) with active disease and 6 (12 percent) with inactive disease had an abnormal outcome (P less than 0.001). Neither medical nor surgical treatment, independent of disease activity, appeared to affect the outcome adversely. Eighteen of 73 (25 percent) patients with quiescent or mild disease relapsed, and seven of 16 patients with some disease activity improved (44 percent). Of 34 patients on medication, nine relapsed (27 percent), and of 39 patients not on medication, nine relapsed (24 percent) (P = N.S.). These results suggest that the outcome of pregnancy is not adversely affected by Crohn's disease. However, patients with active disease at conception and/or during the pregnancy have poorer outcomes independent of the use of medication or requirement of surgery. Neither pregnancy nor medications taken affect the course of the disease.

Adult↗

The release profile of a controlled release preparation of 5-aminosalicylic acid (Rowasa I) in humans.

5-Aminosalicylic acid and its metabolite, N-ac-5-ASA, were measured in the plasma, urine, and ileostomy effluent of 24 ileostomates who ingested 750 mg Rowasa I following an overnight fast. Twelve subjects previously had a small-bowel resection or had part of their small bowel out of circuit (mean 95 cm) (Group I) while 12 had an intact small bowel (Group II). The mean peak plasma concentration of N-ac-5-ASA was 1.11 micrograms/ml in Group 1 subjects compared with 2.80 micrograms/ml in Group II subjects (P = N.S.). On average, 53.0 percent of the ingested Rowasa I was detected in the 24-hr ileostomy effluent of Group I subjects compared with 45.3 percent in the Group II subjects (P = N.S.). The mean recovery of 5-ASA and N-ac-5-ASA in urine was 8.5 percent in Group I and 35.6 percent in Group II subjects (P less than 0.001). These studies demonstrate that 5-ASA is released and present in the small bowel following oral ingestion of Rowasa I in patients who have or have not had small bowel resections.

Administration, Oral↗

Characterization of immune responses in different lymphoid compartments during small intestinal allograft rejection.

In the present study, we examined the sequential changes of procoagulant activity (PCA) in different host and graft tissue compartments in order to assess its role as an immunologic effector and monitor of the rejection process. An early increase in PCA in the graft mesenteric nodes marks the onset of the host-graft immune interaction prior to any PCA or histologic changes in the other tissue compartments. This was followed by increases in PCA in the peripheral blood and graft intraepithelial compartments coinciding with maximal clinical and histologic signs of rejection. Cyclosporin A fully suppressed alloantigen-induced activation of PCA in the intraepithelial compartment and peripheral blood mononuclear cells, but only partially suppressed PCA in graft mesenteric nodes of the allogeneic transplants. The sequence of PCA changes accurately reflected the clinical and histologic changes during allograft rejection. Thus, PCA measured in peripheral blood mononuclear cells appears to be a sensitive and accurate marker of allograft rejection.

Animals↗

The effects of cyclosporine and cyclosporine metabolites in experimental small intestinal transplantation.

Cyclosporine metabolites (CM) were compared with cyclosporine for their in vitro and in vivo immunosuppressive, nephrotoxic, and hepatotoxic effects using (A) in vitro mixed lymphocyte induction of monocyte/macrophage procoagulant activity (PCA), an accurate marker of allograft rejection; (B) in vitro toxic effects on renal cells in culture; and (C) a unidirectional rejection model of rat small intestinal transplantation (SIT). CM were composed of OL1, OL17, OL18, and two additional peaks C and H, (peak C: mass = 1235, 15.3% of total CM, peak H: mass = 1205, 6.3% of total CM). In vitro, CM fully suppressed the one-way mixed lymphocyte culture-induced PCA from 52.5 +/- 8.2 mU/10(6) PBM to the basal level 22.3 +/- 6.6 mU/10(6) PBM (P less than 0.01), which was comparable to CsA (21.3 +/- 5.5 mU/10(6) PBM). Lewis rats that had received Lewis-Brown Norway F1 hybrid intestinal allografts when treated with CM, demonstrated near-normal histology with minimal signs of rejection as compared with the fulminant clinical and histological rejection observed in the control (untreated and Cremaphor/NaCl treated) animals. PCA was markedly elevated in the control animals, 278 +/- 172 (untreated) and 160 +/- 98 mU/10(6) PBM (Cremaphor/normal saline treated), whereas CsA-treated allogeneic transplants expressed only basal levels of PCA (14.0 +/- 4 mU/10(6) PBM) (P less than 0.01), associated with normal histology. CM-treated animals expressed PCA levels of 27.0 +/- 10 mU/10(6) PBM, which was significantly different from both control and CsA-treated animals (P less than 0.01). In contrast to CsA-treated animals, CM-treated allogeneic transplants demonstrated no apparent renal or hepatic toxicity, as measured by blood urea nitrogen (25.3 +/- 9.5 vs. 10.0 +/- 5.3 mg/dl), alkaline phosphatase (160.7 +/- 29.3 vs. 100.3 +/- 19.5 U/L), and aspartate transaminase (96.7 +/- 23.7 vs. 61.7 +/- 11.7 U/L) (P less than 0.01). Similarly, in contrast to CsA, CM had minimal or no toxicity in renal epithelial and mesangial cells in culture, as measured by minimal or no inhibition of DNA, RNA, and protein synthesis. These results suggest that CM have potent immunosuppressive properties with no apparent nephrotoxicity and hepatotoxicity in vitro and in vivo.

Animals↗

Delta6 desaturase inhibition : a novel mode of action of norflurazone.

The herbicide Norflurazone was shown to be an inhibitor of fatty acid of the Delta6 desaturation system. Treating cultures of the microalgae Spirulina platensis or Monodus subterraneus with this herbicide brought about a reduction in the level of gamma-linolenic acid and in an increase in the level of linoleic acid. In Monodus, the increase in linoleic acid made it more available for omega3 desaturation, resulting in an increase in the proportion of eicosapentaenoic acid. The proportion of arachidonic acid did not decrease albeit the drastic decrease in its precursor gamma-linolenic acid.

Journal Article↗