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Biomedical subjects

D B Sachar

Publications and source records attributed to D B Sachar.

At least 91 records · Page 5Linked to original sources
PubMed1985

Extraintestinal cancers in inflammatory bowel disease.

The case histories of 1961 patients with inflammatory bowel disease (IBD), 1227 with Crohn's disease (CD) and 734 with ulcerative colitis (UC), have been studied for the incidence of extraintestinal malignant neoplasms. There were 54 extraintestinal cancers in 51 patients: 28 patients with CD and 23 with UC; 25 men and 26 women. There were 9 breast, 7 skin, 15 reticuloendothelial, 11 genitourinary, 3 lung, 3 perianal, 2 pancreatic islet cell, and several miscellaneous cancers. The number of patient-years from the onset of disease to the last date of follow-up was calculated for men and women with each form of IBD. The observed number (O) of neoplasms was recorded. The expected number (E) of neoplasms was derived from the Department of Health, Education, and Welfare (DHEW) incidence figures for the same neoplasms that occurred in a standard age- and sex-matched population. The O/E ratio was then calculated for each type of cancer as well as for the entire series. There were no statistically significant increases in overall O/E ratios of extraintestinal cancers for either CD (0.76) or UC (1.32). On the other hand, several specific types of cancer did appear to occur with a frequency that was significantly greater than expected. These cancers were classified into two groups. The first group included reticuloendothelial neoplasms. There was an excess of leukemias in UC (P less than 0.005) and an excess of lymphomas in both UC and CD (P less than 0.005). The second group included three squamous cell cancers of the perianal region, an incidence 30 times greater than expected, and two squamous cell cancers of the vagina, also in excess of the expected number. Lymphoma, leukemia, and squamous cell cancers have been reported to occur in excess in immunosuppressed or irradiated patients. It may therefore be speculated that the apparently increased incidence of these neoplasms in the patients with ileitis and colitis might be related to immunologic deficiencies associated with IBD, to the long-term administration of steroids or other immunosuppressive medications that were given to most of the patients or, possibly, to increased exposure to ionizing radiation. The apparently increased incidence of perianal and vaginal cancers of the squamous variety might be a consequence of the combined effects of chronic inflammatory disease involving these areas and primary immune suppression.

Adult↗
PubMed1985

The superior mesenteric artery syndrome. The disease that isn't, or is it?

Intestinal obstruction of the duodenum by entrapment between the aorta and the superior mesenteric artery (SMA) is an uncommon cause of megaduodenum. Despite many case reports, acceptance of the SMA syndrome as a clinical entity has been controversial on account of its confusion with other causes of megaduodenum. We therefore report a case of SMA syndrome which sharply exemplifies its clinical and anatomic features. The clinical findings are proximal duodenal obstruction with an abrupt cutoff and active peristalsis. The anatomic features of this entity are a narrow angle between the aorta and the SMA, together with high fixation of the duodenum by the ligament of Treitz and/or an anomalous SMA crossing directly over the aorta at its intersection with the duodenum. The SMA syndrome may occur as an acute self-limited event due to a reversible precipitating factor, or as a chronic recurring disorder. The acute form subsides with correction of the specific initiating factor; the chronic form responds favorably to simple surgical mobilization of the duodenum.

Adolescent↗
PubMed1985

Outcome of toxic dilatation in ulcerative and Crohn's colitis.

A review of 1,236 patients admitted to The Mount Sinai Hospital with inflammatory bowel disease between 1960 and 1979 yielded 75 cases (6%) with toxic dilatation of the colon. There were 61 cases among 613 patients (10%) with ulcerative colitis (UC), and 14 of 623 (2.3%) with Crohn's disease (CD). Fifty-nine of the 75 patients (79%) underwent surgery during their hospitalization with toxic dilatation. Twelve of the 75 patients (16%) died. Both UC and CD groups had similar mean ages at onset of colitis (32 years and 31 years, respectively) and at development of toxic dilatation (37 years); similar durations of overall disease (4.8 and 5.9 years) and of toxic dilatation prior to surgery (11 days and 13 days); and similar anatomic distributions of disease. Both UC and CD also had similar mortality rates (16% and 14%). Mean duration of presenting attack up to onset of toxic megacolon was longer in CD than in UC (62 days versus 31 days) and in unoperated versus operated cases (64 days versus 37 days), but was not significantly different between survivors and mortalities (43 days versus 39 days). Mortality rates were also unaffected by total duration of inflammatory bowel disease, first attack versus relapse (14% versus 18%), or medical versus surgical therapy (13% versus 17%). Factors which affected mortality included age (30% for patients over 40 years old, versus 5% for those younger than 40), sex (21% in women versus 13% in men), and especially the occurrence of colonic perforation (44% for cases with perforation versus only 2% in those without). Of the 12 patients who died, 11 had suffered colonic perforation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Chlorpropamide-induced cholestatic jaundice and pseudomembranous colitis.

A previously healthy 59-year-old man received chlorpropamide 250 mg/day for adult-onset diabetes. Within 1 month of starting the drug, he developed cholestatic jaundice and pseudomembranous colitis. The colitis worsened during subsequent treatment with multiple antibiotics and sulfasalazine. Oral vancomycin produced a prompt and total remission. One similar case of chlorpropamide toxicity manifested by jaundice and colitis has been previously reported. It is possible that the sulfonamide moiety of the chlorpropamide was implicated in the development of the colitis.

Chlorpropamide↗
PubMed1985

Free perforation in Crohn's disease: I. A survey of 99 cases.

A review of more than 181 reported cases of free perforation in Crohn's disease yielded 84 cases that fulfilled rigorous criteria for classification as spontaneous free perforation with generalized peritonitis. An additional 15 cases from The Mount Sinai Hospital, derived from a population of 1010 patients with Crohn's disease, bring the total number to 99. Separately tabulated are 116 other cases either occurring in bypassed segments, developing after surgery, presenting with ruptured abscesses, or not definitively documented. Most reported perforations in the literature occurred in the distal small bowel. Among the Crohn's disease patients in our hospital, however, the incidence of colonic and small bowel perforation were 1.6 and 0.7%, respectively, with the highest frequency actually occurring in diseased segments of jejunum (2/50 = 4%). Free perforation was the presenting manifestation of the disease in 25 of the 84 reported cases. In our 15 patients, although perforation was never the presenting manifestation, it tended to occur early in the course of the disease (mean 3.5 years from onset of symptoms). Ninety-six of the 99 cases were operated on. The three patients treated without surgery all died. Mortality was most frequent following simple suture in the earliest reported case (39%), but considerably less frequent after resection and anastomosis (3.7%). All 18 patients treated by resection and diversion survived. Immediate surgery with resection and/or diversion therefore appears to be appropriate treatment for free perforation in Crohn's disease.

Adolescent↗
PubMed1985

Pyogenic liver abscess in Crohn's disease.

We describe six cases of pyogenic liver abscess occurring among 1227 Crohn's disease patients admitted to The Mount Sinai Hospital from 1960 through 1982, and review the features of the seven similar cases that have been previously reported. Mechanisms of formation of liver abscess in these 13 patients included direct extension of intraabdominal abscess (three cases), propagation via the portal vein (eight cases), biliary complications (one case), or metastatic cancer (one case). Five of the 13 patients died. All five deaths occurred among the eight patients with multiple abscesses; all five patients with solitary abscess survived. The mean age of the patients who died was 56 years, versus 37 years for the survivors. Three of the four patients treated with antibiotics only died; only two of the nine patients who underwent some form of drainage succumbed. Mortality was usually attributable to failure in making the diagnosis, especially as liver function test abnormalities were often subtle. Furthermore, the generally nonspecific clinical signs and symptoms were often obscured by underlying bowel disease. If a high index of suspicion is maintained, CT scanning and ultrasonography should reveal the lesion at an early stage, so that the necessary drainage procedure can be carried out, with or without concomitant resection of affected bowel and drainage of intraabdominal abscess.

Adult↗
PubMed1984

Course of enterovesical fistulas in Crohn's disease.

Enterovesical fistulas occurred in 38 of 683 patients (5.6 percent) with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1977. There were 22 ileovesical fistulas, 8 colovesical fistulas, and 8 fistulas of combined ileal and colonic origin. These cases fell into three different pathophysiologic categories: 16 patients presented with sepsis after a mean duration of 7 years of Crohn's disease, 19 presented without sepsis after a mean of 10 years of disease, and 3 elderly cancer patients presented with an average 25 years disease duration. Sepsis was usually due to deep pelvic or lower quadrant abscess with spontaneous rupture into the bladder. Nonseptic fistulization was a later, more gradual process, reflecting slow penetration into the bladder from a site of chronic cicatrizing bowel disease. Cancer was a very late complication, arising in each patient from an excluded loop. Although medical treatment was successful in delaying surgery in 6 patients and obviated surgery altogether in 2 patients, 36 of 38 patients (95 percent) eventually required operation. Postoperative mortality in this series was limited to two patients (5 percent) with preoperative intraabdominal abscess and sepsis. Five other deaths, unrelated to urinary complications, were caused by intestinal cancer in three patients and by intestinal complications of recurrent Crohn's disease in two patients. The urologic course of patients with enterovesical fistula was completely benign. All operated patients were cured of their enterovesical fistulas, and no urologic sequelae developed. Subsequent reoperations that were required in 45 percent of these patients were all for recurrent bowel disease and not for fistula or other urologic problems.

Adolescent↗
PubMed1984

Loss of suppressor T-cells in active inflammatory bowel disease.

The proportions and absolute numbers of helper and suppressor T-cells in 40 patients with inflammatory bowel disease and 22 control subjects were determined, using the monoclonal antibodies OKT 4 and OKT 8. There were no significant differences in helper or suppressor cell proportions among 15 steroid treated patients with active inflammatory bowel disease, 10 patients with inactive inflammatory bowel disease, 10 patients with other gastrointestinal diseases, or 12 normal control subjects. In contrast, 15 patients with active inflammatory bowel disease not treated with corticosteroids manifested increased proportions of helper cells and decreased proportions of suppressor cells (p less than 0.001), compared with all other patient groups and to normal controls. When absolute numbers of helper and suppressor subsets were measured, these alterations in proportions of helper and suppressor cells were primarily attributable to decreased counts of suppressor T-cells both in patients with active Crohn's disease and in those with ulcerative colitis (p less than 0.01). In four patients undergoing serial study, the helper/suppressor ratios appeared to rise and fall respectively with clinical exacerbations and remissions of disease. These data provide additional evidence for the involvement of cellular immune systems in these disease processes.

Adolescent↗
PubMed1984

Placebo-controlled clinical trials in gastroenterology. A position paper of the American College of Gastroenterology.

Treatment programs for digestive diseases should be evaluated by randomized clinical trials. Under most circumstances, the best design for such trials requires placebo controls. For example, clinical trials should include groups of placebo-treated patients when there is no commonly accepted standard patients when there is no commonly accepted standard therapy for the disease under study, when standard therapy is of doubtful efficacy, or when standard therapy is unacceptably toxic. Moreover, illnesses--including peptic ulcer and IBD--may have sufficiently high response rates to placebo therapy as to favor placebo-controlled study designs. Placebo treatment is also free of substantial risk, at least compared to active drug treatment, when the disease process is very mild or when the study period is very short. Acceptable alternatives to placebo control include direct comparisons of new agents to standard therapy and addition of either new agents or placebo to a continuing baseline of standard therapy. Similarly, both placebo and active-treatment groups can sometimes be permitted access to standard therapy on a p.r.n. basis, with utilization thereof serving as one of the criteria of therapeutic response. Placebo-controlled trials are therefore generally feasible and desirable methods for testing the safety and efficacy of various proposed treatments for gastrointestinal diseases. High ethical standards in clinical medicine depend on high scientific standards in clinical research.

Clinical Trials as Topic↗
PubMed1983

Surgical treatment, skin test reactivity, and lymphocytes in inflammatory bowel disease.

Sixty-three patients with inflammatory bowel disease were studied before and after bowel resection. Peripheral lymphocytes, T- and B-cell counts, and skin test reactivity to five recall antigens were determined before operation and 6 to 18 months postoperatively. Twenty-eight patients (44 percent) were unable to react to any skin test initially. Anergic patients had significantly lower lymphocyte and T- and B-cell counts. There was no difference in age, severity or duration of disease, or amount of weight loss between anergic patients and those who responded. Also, there was no difference between patients with ulcerative colitis and those with Crohn's disease. After surgery, 25 previously anergic patients became able to react to skin tests. They also showed a significant increase in T and B cells which did not occur in the previously reactive group. However, the overall peripheral lymphocyte and T- and B-cell counts remained well below those of the normal control subjects. Patients with inflammatory bowel disease that requires surgical treatment have significant immunologic abnormalities. Removal of the diseased bowel, weight gain, and cessation of steroid medication improves skin test reactivity but does not correct the depressed peripheral lymphocyte and especially T-cell counts.

Adult↗
PubMed1983

Prostanoid synthesis by cultured intestinal epithelial and mononuclear cells in inflammatory bowel disease.

Intestinal epithelial and mononuclear cells were isolated from normal colonic mucosa and from intestinal mucosa of inflammatory bowel disease patients. Prostanoid synthesis by primary cultures of intestinal mononuclear cells were four to six fold higher than its synthesis by primary cultures of epithelial cells. Prostaglandin E2, prostacyclin and thromboxane A2 synthesis by cultured mononuclear cells isolated from inflamed ileal mucosa of four Crohn's disease patients: 5.6 +/- 1.2; 3.2 +/- 1.9 and 2.4 +/- 1.4 (mean +/- SE) ng/1 X 10(6) cells were significantly higher than their respective synthesis by cultured mononuclear cells isolated from uninflamed ileal mucosa isolated from the same patients: 0.8 +/- 0.1; 0.3 +/- 0.1 and 0.2 +/- 0.03 ng/1 X 10(6) cells or from normal colonic mucosa: 1.5 +/- 0.3; 0.3 +/- 0.1 and 0.5 +/- 0.1 (N = 12) ng/1 X 10(6) cells. Prostanoid synthesis by primary cultures of intestinal mononuclear cells isolated from colonic mucosa of five ulcerative colitis patients was enhanced but not significantly different from its synthesis by cells isolated from normal subjects. These results suggest that the enhanced intestinal prostanoid synthesis in active Crohn's disease is derived from stimulated local mononuclear cells and may have an important role in the pathogenesis of the disease.

Cells, Cultured↗
PubMed1983

Corticotropin versus hydrocortisone in the intravenous treatment of ulcerative colitis. A prospective, randomized, double-blind clinical trial.

Sixty-six patients hospitalized for ulcerative colitis were treated in a prospective, double-blind, clinical trial. They received either 120 U/day of intravenous corticotropin or 300 mg/day of intravenous hydrocortisone. Patients were randomized within strata defined by whether they had received oral corticosteroids continuously for at least 30 days before the study (group A, 35 patients), or whether they had received no such prior treatment (group B, 31 patients). Twenty-eight of the 66 patients (42%) achieved remission. In group B, the proportion of patients entering remission was greater with corticotropin than with hydrocortisone (63% vs. 27%, 0.025 less than p less than 0.05). The opposite trend was observed within group A, for whom hydrocortisone appeared more effective (53% vs. 25%, 0.05 less than p less than 0.10). Impaired adrenal responsiveness, as measured by serum cortisol and dehydroepiandosterone-sulfate levels, did not explain the different responses to therapy within the two study groups. Twenty of 28 patients whose acute therapy was successful were still in remission 1 yr after study. These data suggest that, at the doses used, intravenous corticotropin therapy of severe ulcerative colitis is the more effective choice for those patients not previously treated with corticosteroids, while intravenous hydrocortisone seems preferable for patients already receiving steroid treatment.

Adrenocorticotropic Hormone↗
PubMed1983

Risk factors for postoperative recurrence of Crohn's disease.

To identify potential risk factors that influence postoperative recurrence rates of Crohn's disease, the postoperative recurrence-free survival of 93 patients who underwent their first resections at The Mount Sinai Hospital between 1964 and 1973 has been examined. Features analyzed individually and jointly were age, sex, anatomic location, operative procedure, and preoperative disease duration. In patients with Crohn's colitis, recurrence rates appeared somewhat lower among 11 patients with ileostomy than among 5 patients with anastomosis. In the entire series, recurrence rates were lowest in patients with longest preoperative durations (p = 0.02). This same tendency was especially marked among the 68 patients without ileostomies (p = 0.005). Likewise, among the 38 patients with ileitis, the relative risk of recurrence was significantly lower for those with disease duration exceeding 10 yr (p = 0.01). Relative risk of recurrence in the entire series for patients with 2-yr duration was 1.5 compared with those who had 10-yr duration. This inverse association between preoperative disease duration and postoperative recurrence rate may reflect persisting differences between inherently more aggressive versus more indolent forms of Crohn's disease.

Adult↗
PubMed1982

Intraabdominal abscess in Crohn's (ileo) colitis.

Operations for intraabdominal abscess were performed in 46 (20 percent) of 230 patients with Crohn's colitis and ileocolitis treated at the Mount Sinai Hospital during the decade 1964 to 1974. Internal and external fistulas, intestinal obstruction, and abdominal mass occurred significantly more often in patients with intraabdominal abscess, while only overt bleeding was significantly less common. Abscesses were equally divided between 23 patients who had undergone previous surgery and 23 cases of spontaneous onset. IN ileocolitis, the most frequent site of origin was the terminal ileum with right lower quadrant abscess, as opposed to a sigmoid origin in colitis with presentation in the left lower quadrant. There was no mortality among 24 patients treated with simple drainage, usually for superficial abscess, but enterocutaneous fistulas persisted in 5 of these patients (21 percent). Four of 11 patients (35 percent) died after undergoing bypass or ileostomy diversion. Among the 31 patients surviving either of these procedures, 18 (60 percent) required subsequent resection of the diseased bowel. By contrast, among 11 patients treated with primary en bloc resection plus drainage, there was only 1 death (9 percent) and no abscess recurrence or chronic enterocutaneous fistula formation during a follow-up period of 1 to 4 years. The high mortality rate after bypass may be explained by the more serious nature of the disease and the preexisting deep intraabdominal abscess and postoperative sepsis. Simple extraperitoneal drainage is a safe procedure associated with an extremely low mortality; however, when feasible, resection of the diseased bowel seems to be the treatment of choice for abscess in patients with Crohn's colitis and ileocolitis.

Abdomen↗
PubMed1982

Granulomas do not affect postoperative recurrence rates in Crohn's disease.

Previous studies have reached disparate conclusions on the issue of whether or not granulomas confer any protection against recurrence of Crohn's disease after operation. In an attempt to resolve this controversy, we have examined postoperative recurrence rates in 102 patients with Crohn's disease. There were no differences in cumulative postoperative recurrence-free survival between the 53 patients with granulomas present in the resected specimens and the 49 patients without granulomas. It was concluded that the presence of granulomas in resected specimens of Crohn's disease exerts no independent influence on the rate of postoperative recurrence.

Crohn Disease↗