Sporadic duodenal adenoma is associated with colorectal neoplasia.

OBJECTIVE: The objective of this study was to assess the association between colorectal neoplasia and sporadic duodenal adenoma. METHODS: A retrospective case control study was conducted using the databases of two major teaching hospitals in Western Australia. The frequency of colorectal neoplasia in patients with sporadic duodenal adenomas was compared with that in a control group of patients presenting for endoscopies. The frequency of colorectal cancer in duodenal adenoma patients was also compared with the population incidence. RESULTS: Of 56 sporadic duodenal adenoma patients, 34 (61%) had been colonoscoped. When comparing the findings between patients with sporadic duodenal adenoma and an endoscoped control group, all colorectal neoplasias were significantly more common in the duodenal adenoma group (56% v 33%; odds ratio (OR) 2.4 (95% confidence intervals (CI) 1.1-5.4)). Although finding either advanced colorectal adenoma or cancer was also more common in duodenal adenoma patients (38% v 19%; OR 2.3 (95% CI 1.0-5.2)), as was finding colorectal cancer alone (21% v 8%; OR 3.0 (95% CI 1.0-9.1)), the results were not statistically significant. However, the incidence of colorectal cancer was much greater in duodenal adenoma patients than in the population (p<0.001). CONCLUSIONS: Sporadic duodenal adenoma has a clinically important association with colorectal neoplasia. Thus patients with duodenal adenomas should undergo colonoscopy to detect colorectal neoplasia.

Human chorionic gonadotropin exhibits potent inhibition of preterm delivery in a small animal model.

OBJECTIVE: The purpose of this study was to test the capability of human chorionic gonadotropin to inhibit prostaglandin-induced preterm delivery in a murine model. STUDY DESIGN: A preterm delivery model was developed by using intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) to induce preterm labor in C3H/HeN inbred mice. Mice were then pretreated with human chorionic gonadotropin 4 hours before administration of prostaglandin F(2)(alpha), and time to delivery of the first pup was recorded. After initial promising results, mice were then given increasing intraperitoneal doses of human chorionic gonadotropin (100 IU, 250 IU, or 1000 IU or sodium chloride solution vehicle) 4 hours after administration of prostaglandin F(2)(alpha). The specificity of the human chorionic gonadotropin effect was assessed by treating mice with whole human chorionic gonadotropin, an equal mass dose of the beta-subunit or the alpha-subunit of human chorionic gonadotropin, or an equal mass dose of luteinizing hormone 4 hours after administration of prostaglandin F(2)(alpha). Delivery times between groups were compared by using the Mann-Whitney U test and the log-rank test. Survival estimates were computed by using the Kaplan-Meier method. RESULTS: Pilot studies in 52 mice confirmed that a single intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) on day 16 (80% gestation) consistently induced preterm delivery compared with the effect of sodium chloride solution on control mice (prostaglandin F(2)(alpha), 19.3 +/- 2.9 hours; sodium chloride solution, 53.5 +/- 13.6 hours; P <.0001). Mice pretreated with human chorionic gonadotropin (1000 IU) demonstrated significant delays in delivery times compared with the prostaglandin-only group (prostaglandin F(2)(alpha) only, 21.9 +/- 2. 0 hours; human chorionic gonadotropin pretreatment plus prostaglandin F(2)(alpha), 48.5 +/- 20 hours; P <.0001; n = 17). Mice treated with human chorionic gonadotropin (100 IU, 250 IU, 1000 IU) 4 hours after administration of prostaglandin F(2)(alpha) demonstrated significant dose-dependent inhibition of preterm delivery compared with the prostaglandin-only group (P <.00005; n = 34). Mice treated with the alpha-subunit or the beta-subunit of human chorionic gonadotropin after prostaglandin administration did not demonstrate delays in delivery times (P =.46; n = 27). Administration of luteinizing hormone delayed delivery compared with the effect of prostaglandin F(2)(alpha) on control animals (P <.05; n = 17); however, the effect was less pronounced than that seen with a mass equivalent of human chorionic gonadotropin. CONCLUSIONS: Human chorionic gonadotropin exhibits potent inhibition of prostaglandin-induced preterm delivery in mice. The effect is dose-dependent, and whole human chorionic gonadotropin is required to elicit inhibition. Further studies are needed to determine the safety and efficacy of human chorionic gonadotropin as a potential therapy for preterm labor inhibition in human pregnancy.

Comparative costs of metal versus plastic biliary stent strategies for malignant obstructive jaundice by decision analysis.

BACKGROUND: For palliation of patients with malignant obstructive jaundice, expansile metal stents provide longer patency than plastic stents but are more expensive. The optimal cost-effective strategy has not been established. Our aim was to compare the relative costs of 3 strategies: (1) plastic stent, with exchange on occlusion; (2) metal stent initially, with coaxial plastic stent insertion in the event of occlusion; or (3) plastic stent initially, with metal stent exchange in the event of occlusion. METHODS: A decision analysis model was created using DATA 2.6 software to assess the relative costs of the three strategies. Values for variables including the probabilities of reintervention and patient survival were obtained from published data. Costs were based on Medicare reimbursements of hospital charges, and the model was evaluated from the perspective of a third-party payer. One-way and two-way sensitivity analysis of the variables was performed over a wide range. RESULTS: The outcome is highly sensitive to the ratio of metal stent cost relative to endoscopic retrograde cholangiopancreatography cost (cost ratio M:ERCP) and to the length of survival of the patient. The most economical strategies were (2), (3) and (1) for M:ERCP cost ratios of <0.5, 0.5 to 0.7, and >0.7, respectively. CONCLUSIONS: The choice of stent should be guided by the relative local costs of ERCP and metal stents and by the prognosis of the patient. At current metal stent costs and Medicare reimbursement rates, initial placement of a plastic stent, followed by metal stent placement at first occlusion in longer survivors, is an economical option. If metal stent cost is less than half of ERCP cost, then initial insertion of a metal stent would be most economical. Use of plastic stents is preferable for patients surviving less than 4 months, whereas metal stents are more economical for patients with longer survival.

The effect of interleukin-10 and transforming growth factor beta-1 on HLA-DR expression in colonic epithelial cells.

The aim of this study was to assess whether interleukin-10 (IL-10) and/or transforming growth factor beta-1 (TGFbeta1) downregulate HLA-DR expression using the HT29 cell line as a model of colonic epithelial cells. HLA-DR expression was induced in HT29 cells with gamma-interferon. The effects of IL-10 alone, TGFbeta1 alone, and IL-10 and TGFbeta1 in combination were studied. HLA-DR expression was assessed using flow cytometric analysis. Gamma-interferon induced HLA-DR expression in a dose-dependent fashion. In the absence of gamma-interferon, neither IL-10 nor TGFbeta1 induced HLA-DR expression. In isolation, neither IL-10 nor TGFbeta1 downregulated HLA-DR expression. When IL-10 and TGFbeta1 were added in combination, small (6-30%) statistically significant reductions in HLA-DR expression were seen. The biological significance is unclear.

Review article: treatment of Clostridium difficile infection.

AIM: A systematic review of controlled trials of therapy of Clostridium difficile intestinal infection using methodology described by the Cochrane Collaboration. METHODS: Trials were identified by searching computer databases over the years 1978-1996. Trials were included if they were (a) prospective randomized, controlled trials and (b) included patients with symptomatic disease. The primary end-point was clinical resolution of diarrhoea. Secondary end-points were clinical relapse and stool clearance of C. difficile and C. difficile toxin. RESULTS: Nine trials (469 patients) satisfying the inclusion criteria were identified. Two trials were placebo controlled. Six trials compared vancomycin to other antibiotics (fusidic acid, bacitracin, teicoplanin and metronidazole). For clinical resolution response rates ranged from 21 (placebo) to 100% (vancomycin). On pooling the trials, no antibiotic showed clear therapeutic superiority. Rates of clinical relapse ranged from 5 to 42%. Only one trial showed significant advantage of one antibiotic over another for prevention of relapse (teicoplanin vs. fusidic acid). CONCLUSION: The published data are limited, and further studies are required.

Cytokines and mechanisms of action of glucocorticoids and aminosalicylates in the treatment of ulcerative colitis and Crohn's disease.

Medical therapy of ulcerative colitis and Crohn's disease involves the control of active inflammation to obtain clinical remission and then maintaining that remission. Corticosteroids and 5-aminosalicylic acid are the mainstay of such management. Both have a wide range of properties and are able to inhibit many effector mechanisms which are potentially involved in mucosal inflammation. In in vitro assays, both are able to inhibit the release of a wide variety of pro-inflammatory and immunoregulatory cytokines. In vivo, such effects would limit tissue damage, prevent further amplification of the immune response and restore epithelial function.

Exposure to grain dust and changes in lung function.

Respiratory symptoms and lung function were assessed in 41 seasonal grain handlers and related to duration of employment and level of exposure to grain dust. Ten public works department employees, not exposed to grain dust, were examined during the same period. Respiratory symptoms, forced expired volume in one second (FEV1), and bronchial responsiveness (dose of methacholine provoking a 20% fall in FEV1-PD20) were assessed before starting work and at weekly intervals during a period of employment lasting up to four weeks. Two atopic grainhandlers with pronounced bronchial hyperresponsiveness (PD20 less than 1 mumol) and a history of asthma withdrew from the study within two weeks because they developed severe asthma. Respiratory symptoms were more frequent and more often attributed to work in the grainhandlers than in the non-exposed subjects. In the grainhandlers the FEV1 decreased by a mean (95% confidence intervals) of 321 ml (198-444) (p less than 0.05) and the mean (95% confidence interval) PD20 decreased from 20.6 mumol (10.3-41.2) to 6.0 mumol (2.8-12.5) (p less than 0.05) after one week of work. Over the next three weeks the mean FEV1 returned towards the prestudy values. The mean PD20, however, remained significantly lower than the initial value. The mean FEV1 and PD20 did not change significantly in the non-exposed subjects. The frequency of symptoms and decreases in FEV1 were greater in grainhandlers when working in jobs where total exposure to dust was greater than 20 mg/m3 than when working in jobs where it was less than 10 mg/m3. The results indicate that occupational exposure to grain dust results in respiratory symptoms and changes in lung function, including increased airway responsiveness, within the first week of exposure to grain dust at work. These changes appear to be determined by the degree of dust exposure and suggest a direct effect of grain dust on the lung in these subjects.

An autoradiographic technique for en-face preparations of aortic endothelium.

A method for the en-face preparation of aortic endothelium was developed from various different published accounts of the technique. This was adapted for autoradiography. Eighteen mice had tritiated thymidine (1 microCi/g body weight) injected and were killed 1 day later. Perfusion fixed aortae were cut into segments and placed face down on gelatin-coated slides. The arterial media and adventitia were removed and the en-face preparations coated with autoradiographic stripping film. After an exposure of 12 weeks the autoradiographs were developed and stained with Harris' haematoxylin. Labelled endothelial cells were clearly distinguishable and there was no distortion of the cells compared with other en-face and whole mount preparations. The technique described is simple, reliable and produces consistent results.

Endometrial cyst of the pancreas.

A 36-yr-old woman with a history of epigastric pain and a recent episode of acute pancreatitis was found at surgery to have a cyst in the tail of the pancreas that was lined by ectopic endometrial tissue. This is, to our knowledge, the first recorded case of endometriosis of the pancreas. The clinicopathologic features of this patient and the possible pathogenesis of her most unusual pancreatic lesion are discussed.

Rectal biopsy in early Lymphogranuloma venereum proctitis.

Two cases of early Lymphogranuloma venereum (LGV) proctitis are presented, with discussion of the histopathologic findings of the rectal biopsy specimens. Emphasis is placed on the need to recognize this condition in the early stage of inflammation, before the development of stricture, so that complete cure can be effected.

Fat embolism syndrome in delirium tremens.

Delirium tremens in a common feature in the alcoholic population. The Fat Embolism Syndrome (FES) is characterized by fever, encephalopathy, respiratory failure and skin petechiae. Fat embolism has been associated with alcoholics but the diagnosis was apparent only at autopsy. We present an alcoholic male who developed delirium tremens unresponsive to therapy, followed by features of the FES. Asterixis and Korsakoff's psychosis are newly described features of this syndrome. Corticosteroids were a definitive therapy in this case.