Biomedical subjects
A Forbes
Publications and source records attributed to A Forbes.
Jejunal water and electrolyte transport in human cryptosporidiosis.
Cryptosporidiosis may have severe clinical consequences in both immunocompromised and immunocompetent individuals. However, pathophysiological mechanisms that are responsible for diarrhea are poorly understood. We performed jejunal perfusion studies in patients with human immunodeficiency virus-related cryptosporidial diarrhea to measure water and electrolyte transport in vivo. Five patients with human immunodeficiency virus-related cryptosporidiosis and nine healthy volunteers were studied using a triple-lumen steady-state jejunal perfusion technique. Stool volume measurement and distal duodenal biopsy showed that the patients had diarrhea (600-1500 ml/24 hr) and morphological abnormalities of small intestinal mucosa. Net water, sodium, and chloride movement in the jejunum was not significantly different from healthy controls. In these patients with watery diarrhea and morphological mucosal abnormalities, we found no evidence that cryptosporidial diarrhea was due to a secretory state in the proximal small intestine. We conclude that diarrhea may be due to secretion of electrolytes and water efflux more distally or to other abnormalities of gastrointestinal function.
Pneumatosis coli: a proposed pathogenesis based on study of 25 cases and review of the literature.
Pneumatosis coli is a rare condition characterised by multiple gas-filled cysts within the bowel wall. We present 25 cases treated over the past 30 years. The patients' mean age was 59 years: 15 were female. Presenting symptoms included diarrhoea (n = 17), mucus discharge (n = 17), rectal bleeding (n = 15) and constipation (n = 12). Pneumatosis usually affected the left colon (96%), and diagnosis was by sigmoidoscopy and biopsy in 18 cases (72%). Pneumatosis coli was associated with psychiatric disorders (36%), chronic lung disease (20%) and colitis (12%). A redundant sigmoid colon was observed in 80% of cases on contrast radiology. Five patients had mucosal pseudolipomatosis on histological examination. Histological and immunohistochemical review indicated that the cysts were lined by cells of macrophage/monocyte phenotype and that many similar mononuclear cells were present in the adjacent submucosa and overlying mucosa. Treatment with antidiarrhoeals and anti-inflammatory drugs in 14 patients resulted in improvement in 9 cases (64%). Oxygen therapy (n = 9) always alleviated symptoms. There was a high recurrence rate (50-78%), but with further courses of therapy lasting remission was achieved in five patients. Two patients underwent colectomy. The associations of pneumatosis coli with psychiatric disorders and mucosal pseudolipomatosis are new and of possible pathogenetic significance. A novel pathogenetic mechanism is suggested to explain the association of pneumatosis coli and chronic respiratory disorders. A model of pneumatosis coli linking some of the apparently disparate pathogenetic theories is proposed.
Mismatch repair function and neoplasia in ulcerative colitis.
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Joint symptoms after restorative proctocolectomy in ulcerative colitis and familial polyposis coli.
We have determined the incidence and nature of joint symptoms in patients who had a restorative proctocolectomy and ileal reservoir for ulcerative colitis (UC) and familial adenomatous polyposis (FAP); we also have recorded the effect of drug treatment and surgery on these symptoms. One hundred seventy-three patients with UC and 25 patients with FAP who had undergone a restorative proctocolectomy answered a questionnaire about joint symptoms. These were present in 96 (55%) patients with UC and five (20%) with FAP. In the 69 patients with UC with joint symptoms before proctocolectomy, 31 (45%) reported improvement after colectomy. However, in 27 (28%) patients with UC and joint symptoms, and four of five patients with FAP with joint symptoms, these started after restorative proctocolectomy. A family history of joint symptoms did not predispose to the development of arthropathy in the patients with UC but may have in patients with FAP. Before colectomy, in most patients with colitis, azathioprine or sulfasalazine did not improve joint symptoms, but steroids were effective in 18 of 64 patients who had received them. Of 101 patients (43%) with joint symptoms in either disease, 43 had symptoms sever enough to interfere with daily activities. We conclude that joint symptoms are a major cause of morbidity in patients with UC. After restorative proctocolectomy they may develop de novo in patients with either UC or FAP.
Frequency and significance of proximal extension of distal ulcerative colitis.
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Absence of skin sensitivity to oxides of aluminium, silicon, titanium or zirconium in patients with Crohn's disease.
BACKGROUND: Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn's disease. Zirconium compounds can be ingested in toothpaste. AIM: To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn's disease. SUBJECTS: Eight patients with Crohn's disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls. METHOD: Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later. RESULT: A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject. CONCLUSION: No support was found for the hypothesis that Crohn's disease is due to a specific sensitivity to ingested metallic or silicon compounds.
Tobacco smoking and alcohol consumption as risk factors for glioma: a case-control study in Melbourne, Australia.
OBJECTIVE: To investigate possible associations between tobacco smoking and alcohol consumption and the risk of adult glioma. DESIGN: This was a population based, case-control study. Relative risks (RR) were estimated using logistic regression analysis. SETTING: Melbourne, Australia. PARTICIPANTS: These comprised 416 case subjects (166 women, 250 men), 66% of those eligible; and 422 control subjects (170 women, 252 men), 43.5% of those potentially eligible. RESULTS: There was no increase in risk of glioma with having ever smoked tobacco (RR 1.29, 95% CI 0.95, 1.75) for all subjects, adjusted for age, a reference date, and gender. There was a slight increase in risk for men (RR 1.64, 95% CI 1.1, 2.45), but not for women (RR 0.99, 95% CI 0.62, 1.62). For men, there was no increase in risk with increasing pack-years of cigarette smoking, but the risk was significantly increased in subjects who had smoked for less than 10 years. There was no increase in risk associated with having ever drunk alcohol for all subjects (RR 0.96, 95% CI 0.67, 1.37), women (RR 0.69, 95% CI 0.4, 1.15) or men (RR 1.40, 95% CI 0.81, 2.43). CONCLUSIONS: This study does not support an association between either tobacco smoking or alcohol consumption and glioma. The pattern of risk associated with tobacco smoking in men appears inconsistent with a causal role, and may be due to chance, response bias, or uncontrolled confounding.
Risk factors for cerebral hemorrhage in the era of well-controlled hypertension. Melbourne Risk Factor Study (MERFS) Group.
BACKGROUND AND PURPOSE: Given that hypertension is now relatively well controlled and use of antiplatelet agents has increased, our primary aims were to investigate the risk of intracerebral hemorrhage (ICH) associated with hypertension and use of antiplatelet agents. METHODS: In this city-wide case-control study, 370 consecutive cases of primary ICH, verified by CT or autopsy, were identified from one of 13 Melbourne hospitals. Ten subjects (or their next of kin) could not be located and 29 refused to participate, resulting in 331 eventual cases. Patients were aged between 18 and 80 years and had no prior stroke. Population-based control subjects were individually age- (+/- 5 years), sex-, and geographically matched to subject cases. A questionnaire administered to participants (or next of kin) elicited information about prior exposure to various potential risk factors. RESULTS: Hypertension approximately doubled the risk of ICH (odds ratio, 2.55; 95% confidence interval, 1.72 to 3.79). The use of aspirinlike drugs, in doses used for secondary prevention of ischemic stroke or cardiac disease, was not associated with an increased risk of ICH (odds ratio, 0.66; 95% confidence interval, 0.20 to 2.21). Factors associated with a reduced risk of ICH were a history of cardiovascular disease, arthritis, or high cholesterol level; being moderately overweight or using hormone replacement therapy; and drinking coffee. CONCLUSIONS: Hypertension was the most important risk factor for ICH but not as high as previously reported, nor was it higher than that reported for ischemic stroke. There was no evidence for any association between the use of aspirinlike drugs and ICH.
Wheelchair use: a physical sign in gastroenterological practice.
Diagnosis of functional abdominal pain requires exclusion of organic causes, and many patients undergo considerable investigation. A positive physical sign supporting a functional diagnosis could therefore be of benefit. Wheelchair use specifically for abdominal symptoms was suspected to represent such a sign. Review of 300 consecutive new referrals to a gastroenterology clinic revealed 10 wheelchair users. In four women the chair was used because of the abdominal condition. The final diagnosis (with follow-up to at least 12 months) was functional abdominal pain in each of these cases. All four had had surgery without symptom relief, and all had used their chairs intermittently (mainly for social occasions and hospital visits) for at least 12 months. They believed that normal walking was rendered impossible by abdominal pain whereas the other six wheelchair users gave a clear account of lower limb pain or weakness. Secondary gain with reinforcement of the 'sick role' was felt to be the probable explanation for wheelchair use in the former group. Wheelchair attendance at the gastroenterology clinic, in the absence of lower limb symptoms, is a rare observation but one that may usefully be added to criteria for diagnosis of a functional disorder.
Finally--international endorsement of a non-condom HIV prevention alternative.
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Leiomyosarcoma of the pulmonary vein.
OBJECTIVE: We report a case of leiomyosarcoma (LMS) of the pulmonary vein and comment on the natural history and determinants for survival for this rare condition. EXPERIMENTAL DESIGN: Our retrospective review is only the fourth such case reported in the world's literature. SETTING: A teaching hospital with an active surgical residency program. PATIENT OR PARTICIPANT: A 61-year-old female who presented with a central pulmonary mass. INTERVENTIONS: Complete resection without pneumonectomy of cardiopulmonary bypass. Pathology showed low grade LMS. MEASURES: Determinants for survival include complete surgical resection and a low mitotic activity of the tumor. RESULTS: The patient remains no evidence of disease three years following initial treatment. CONCLUSIONS: One reported case of LMS of the pulmonary vein had favorable determinants for survival; complete surgical resection and low mitotic activity of the tumor. These factors may have contributed to the successful outcome. The natural history of LMS of the pulmonary vein appears similar to the more widely studied LMS of the inferior vena cava.
Smoking and inflammatory bowel disease.
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Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers.
OBJECTIVE: To assess the efficacy and safety of a repeat course of treatment with transdermal nicotine for cessation of smoking in a brief intervention setting. STUDY DESIGN: Randomised, double blind, placebo controlled trial with follow up for 26 weeks. SUBJECTS: 629 smokers who had unsuccessfully attempted to stop smoking by using active transdermal nicotine and brief behavioural counselling. Smokers were motivated to quit smoking for a second time and smoked > or = 15 cigarettes a day. INTERVENTIONS: Twelve weeks' treatment with active transdermal nicotine patches or placebo and brief counselling at monthly visits. MAIN OUTCOME MEASURE: Sustained smoking cessation for the 28 days before the visit at week 12 verified by expired carbon monoxide concentrations. RESULTS: At 12 weeks 21/315 (6.7%) subjects allocated to active treatment had stopped smoking compared with 6/314 (1.9%) allocated to placebo (absolute difference 4.7%; 95% confidence interval 1.6% to 7.9%; P = 0.003). At 26 weeks the rates were 20/315 (6.4%) and 8/314 (2.6%) (3.8%; 0.6% to 7.0%; P = 0.021). Difficulty in sleeping was reported by 43/179 (24.0%) on active treatment and 19/143 (13.3%) on placebo (P = 0.015). Severe reactions at the site of application were rare (6/322; 1.9%). CONCLUSIONS: Repeated treatment with transdermal nicotine together with brief counselling can improve the low success rates of smoking cessation in recently relapsed, moderate to heavy smokers. Questions remain about whether more intensive interventions or higher doses of nicotine could be more effective. The likelihood of severe reactions at the site of application with repeated treatment is low.
CD44v6 and CD44v3 expression in ulcerative colitis and Crohn's disease.
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Hand-genital transmission of genital warts? An analysis of prevalence data.
The role of hand-genital transmission in the aetiology of genital warts is unclear. However this route is suggested by a number of observations including the relatively high proportion of genital warts in children which contain HPV types 1-4 (15% for children and 2% for adults). We compared two transmission models; one which assumes that hand-genital transmission occurs and one that it does not, and determined the conditions in which each model can reflect the available prevalence data. Hand-genital transmission provides a simple explanation of the observed differences in the proportions of genital warts containing HPV types 1-4 and 6/11 in children and adults. If hand-genital transmission does not occur, the observed difference could only be explained by an eightfold greater probability of transmission to children of types 1-4 than types 6/11, or by an eightfold greater duration of infection with types 1-4. Our findings provide support for the view that genital warts may be transmitted by hand-genital contact.
5-aminosalicylates in inflammatory bowel disease--the more the merrier?
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Review article: the risks of malignancy from either immunosuppression or diagnostic radiation in inflammatory bowel disease.
Inflammatory bowel disease is associated with an increased risk of gastrointestinal malignancy. There has been concern that either diagnostic medical radiation and long-term drug therapy--particularly immunosuppression--might contribute to this increased cancer risk. For the major drug groups (5-aminosalicylates, steroids and immunosuppressants) data are scant but broadly reassuring. Only azathioprine (including 6-mercaptopurine) has been investigated at all carefully. Short- to medium-term therapy probably poses a very slightly increased risk of malignancy which is easily accepted given the current limitation of this agent to second-line use. Continuous therapy for more than two years is much less well documented, and caution should be maintained. A hypothetical model based on data from occupational radiation exposure has been constructed; this permits reasonable confidence that the medical use of ionising radiation contributes a negligibly increased risk of malignancy overall, and is particularly unlikely to add significantly to the incidence of gastrointestinal malignancy.