Biomedical subjects
A Forbes
Publications and source records attributed to A Forbes.
Prospective study of factors predicting outcome of transdermal nicotine treatment in smoking cessation.
OBJECTIVE: To assess the factors associated with cessation of smoking with transdermal nicotine and brief behavioural counselling. DESIGN: Interviews, treatment, and follow up for 26 weeks. SUBJECTS: 1481 subjects recruited by mass media publicity who smoked > or = 15 cigarettes a day and were motivated to stop smoking. INTERVENTIONS: Twelve weeks' treatment with transdermal nicotine and brief behavioural counselling at monthly visits. MAIN OUTCOME MEASURE: Sustained smoking cessation for the 28 days before the visit at week 26 verified by expired carbon monoxide concentrations. The logistic regression analysis included all subjects. RESULTS: Most subjects were dependent on nicotine, and the mean (SD) number of cigarettes smoked a day was 32 (12). Overall, 316/1481 subjects (21.3%) stopped smoking. Factors associated with stopping were being male (adjusted odds ratio 2.0; 95% confidence interval 1.5 to 2.7), age > or = 40 years (1.5; 1.1 to 2.0), living with a spouse or partner (1.5; 1.1 to 2.1), motivation ("want to quit" 1.7; 1.2 to 2.3), and concern about weight gain (1.7; 1.3 to 2.2). Negative associations were smoking marijuana (0.4; 0.2 to 0.8) and the presence of other smokers in the household (0.8; 0.6 to 0.9). Almost all subjects who smoked three or more cigarettes in the first four weeks of treatment resumed smoking in the long term (525/547, 96%). CONCLUSIONS: Age, sex, marital status (living with a spouse or partner), motivation, concern about weight gain, recent marijuana smoking, and other smokers in the household were baseline factors associated with differences in outcome of smoking cessation attempts. Smoking three or more cigarettes in the first few weeks after stopping strongly predicted long term relapse.
A placebo-controlled study of three clonidine doses for smoking cessation.
BACKGROUND AND OBJECTIVE: Clonidine in doses of 150 to 450 micrograms per day has been reported to reduce symptoms of craving associated with tobacco withdrawal and, in some cases, to improve long-term abstinence rates of smoking cessation programs. However, subjects frequently experienced symptoms of dry mouth and drowsiness. This study investigated the lower end of the effective dose range of clonidine for smoking cessation to identify the lowest useful dose and thus minimize the adverse effects of the drug. METHODS: A randomized, double-blind, four-way crossover design compared the effects of clonidine doses or placebo within individual subjects for 4 consecutive weeks. Smokers who were highly nicotine dependent were randomly assigned to different sequences of placebo and 300, 200, and 100 micrograms clonidine per day. Subjects were treated for 4 days of each treatment week and began smoking cessation from the end of day 2. Smokers recorded withdrawal symptoms on multiple visual analog scales during days 3 and 4 before resuming normal smoking until the next period of smoking cessation. RESULTS: A statistically significant dose-response effect was found for craving scores (dose-response gradient, -3.8/100 micrograms; 95% confidence interval [CI], -6.2 to -1.5; p = 0.002) but not for pooled tobacco withdrawal scores. The dose of 300 micrograms per day reduced mean craving scores significantly (-16%; 95% CI, -31% to -1%). Dosing with 200 micrograms approached statistical significance (-14%; 95% CI -30% to 1%) but dosing with 100 micrograms did not (-6%; 95% CI, -22% to 9%). Troublesome adverse experiences were reported by more than 67% of subjects during 200 and 300 micrograms dosing. CONCLUSIONS: This study showed a statistically significant dose-response effect of clonidine on tobacco withdrawal craving and a reduction in mean craving scores of 16% during 300 micrograms dosing. However, its clinical usefulness is doubtful because of frequently reported adverse experiences.
Calcipotriol inhibits rectal epithelial cell proliferation in ulcerative proctocolitis.
Vitamin D3 reduces human rectal crypt cell production rate (CCPR) and may thereby protect against colorectal cancer. Cell turnover is increased in ulcerative proctocolitis, which might therefore respond to vitamin D3 metabolites. This study investigated the effect of calcipotriol, a synthetic vitamin D3 analogue that avoids hypercalcaemia, on human rectal CCPR in ulcerative proctocolitis. Paired rectal biopsy specimens from seven patients with severe disease were established in organ culture with or without calcipotriol (1 x 10(-6) M). After 15 hours, vincristine (0.6 microgram/ml) was added to induce metaphase arrest, and CCPR was determined by linear regression analysis of accumulated metaphases. Compared with values in 17 controls with incidental anal conditions, median rectal CCPR was 28% higher in ulcerative proctocolitis: 5.90 (5.00-9.50) v 4.80 (2.85-7.07) cells/crypt/hour (p < 0.01). Calcipotriol reduced CCPR by 62% in patients with ulcerative proctocolitis, from 5.90 (5.00-9.50) to 2.21 (0.81-3.22) cells/crypt/hour (median with range) p < 0.01. Thus calcipotriol can dampen the hyperproliferative state in ulcerative proctocolitis and could have a therapeutic role in the control of this inflammatory condition.
Association between Meckel's diverticulum and Crohn's disease: a retrospective review.
The operation notes and pathology records of 294 consecutive patients who had right hemicolectomy for Crohn's disease were reviewed. A Meckel's diverticulum was found in 17 (5.8%) of these patients, 2-3 times the expected rate in the general population. At least 50% of diverticula in the normal population contain heterotopic mucosa, but none was found in those diverticula that were examined from this group. The increased prevalence of Meckel's diverticulum in patients with Crohn's disease confirms previous anecdotal reports, but the cause for the increased frequency remains unexplained. The significance of this finding is discussed.
Human papillomavirus infection and its relationship to recent and distant sexual partners.
OBJECTIVE: To determine the relation between the detection of genital human papillomavirus (HPV) DNA and the number of new sexual partners in the last year, 1-5 years, and 5-10 years. METHODS: In a cross-sectional study, 298 women collected tampon specimens and completed self-answer questionnaires on the known risk factors for HPV infection, including the number of sexual partners during the last 1, 5, and 10 years. The tampons were analyzed for the presence of HPV DNA by polymerase chain reaction using L1 consensus primers. RESULTS: Ninety-two (30.9%) tampons were positive for HPV DNA. In univariate analysis, the presence of HPV DNA was associated with a younger age, single marital status, a previously abnormal or currently abnormal Papanicolaou smear, and one or more new sexual partners in the last year, 1-5 years, and 5-10 years. The presence of HPV DNA was not associated with education level, past pregnancy, current or past oral contraceptive use, or the age at first intercourse. In multivariate analysis, only the number of sexual partners during the last year and 1-5 years, and a previously abnormal Papanicolaou smear were associated with HPV. CONCLUSION: The presence of HPV DNA is best predicted by the number of new sexual partners in the last 5 years. Transiently detectable HPV DNA is one possible explanation for this observation.
Acid secretion from a Meckel's diverticulum: the unsuspected mimic of Crohn's disease?
The commonest causes of ulceration in the terminal ileum are Crohn's disease, infection, and neoplasia. Meckel's diverticulum is said to be found more commonly in patients with Crohn's disease than in the general population. We describe a patient who developed extensive terminal ileal ulceration caused by acid secretion from gastric mucosa within a Meckel's diverticulum, a condition that has not been recognized before. Our patient demonstrated a number of clinical features that would be consistent with Crohn's disease, and we wonder whether the rare condition of "Meckel's ileitis" is occasionally misdiagnosed as Crohn's disease in other patients.
Risk factors for development of flucloxacillin associated jaundice.
OBJECTIVES: To identify risk factors predisposing to the development of flucloxacillin associated jaundice. DESIGN: Case-control study. Medical records of cases and controls were reviewed and information recorded on standard data collection forms. SETTING: Alfred Hospital recruiting subjects from Melbourne, Sydney, and Brisbane. SUBJECTS: Cases were defined as patients who had developed jaundice within eight weeks of stopping flucloxacillin, biochemical test results suggesting cholestasis, normal calibre bile ducts, and not been taking recognised hepatotoxic drugs. 51 of the 53 patients referred were included in the study. Four controls for each case were randomly selected from the patient register of the prescribing doctor. These were defined as patients who had been prescribed flucloxacillin without developing jaundice. MAIN OUTCOME MEASURES: Demographic characteristics, medical history, indication for flucloxacillin, dose, route and duration of treatment, other drugs, smoking, and previous drug allergies or use of flucloxacillin. RESULTS: Increasing age and a prolonged duration of flucloxacillin treatment were found to be risk factors for the development of jaundice. Patients aged over 55 years had an odds ratio of 18.61 (95% confidence interval 5.16-67.17) compared with patients under 30. The odds ratio for patients prescribed flucloxacillin for over 14 days was 7.13 (2.90 to 17.58) compared with patients treated for 14 days or less. Dose and route of administration were not related to the risk of jaundice. CONCLUSIONS: Older patients and those receiving flucloxacillin for longer than two weeks are at a substantially greater risk of jaundice. Careful consideration of the risk-benefit ratio is required when flucloxacillin is used in these settings.
CD44 is associated with proliferation in normal and neoplastic human colorectal epithelial cells.
Flash-frozen biopsies obtained from surgical specimens of three adenomatous polyps and 22 colorectal adenocarcinomas (19 primary and three metastatic) were tested by immunohistochemistry for CD44 expression using F10-44-2 monoclonal antibody. CD44 positivity was correlated with proliferative status defined by Ki-67 monoclonal antibody reactivity. In normal colonic mucosa, CD44 was expressed in the proliferative zone of crypts. In tumours, CD44 expression was associated with proliferative areas irrespective of tumour stage or differentiation. Non-proliferating areas of the carcinomatous epithelium did not express CD44 although non-proliferating stromal lymphoid tissue did. There was no apparent association with tumour progression. F10-44-2-defined CD44 is consistently expressed during proliferation by normal colorectal epithelial cells and by both benign and malignant colorectal tumour cells.
Radiological and pathological features of AIDS-related polypoid cholangitis.
A review of the radiographs obtained at ERCP from 31 patients with AIDS-related sclerosing cholangitis (ARSC) demonstrated intraluminal polypoidal defects within the common bile duct and larger intrahepatic ducts in eight cases (26%). The radiological features from this subgroup are described and correlated with the microbiological and histological findings from biopsy specimens including two patients who underwent post-mortem examination. At microscopy the polypoid lesions were demonstrated to consist of granulation tissue. The presence of these polyps did not adversely affect the prognosis nor were they associated with any particular infective agent. We propose recognizing the existence of this entity by the term AIDS-related polypoid cholangitis (ARPC).
Controlled trial of antithrombin III supplementation in fulminant hepatic failure.
Patients with fulminant hepatic failure have severe circulatory disturbances which may be due to fibrin and cellular plugs in micro-vessels which are a consequence of intravascular coagulation and which can lead to multiorgan failure. Since antithrombin III supplementation has been shown to be beneficial in animal models of septic shock with disseminated intravascular coagulation, a controlled study was performed to investigate the effect of antithrombin III supplementation in fulminant hepatic failure. Twenty-five patients in grade III or IV coma were selected on the basis of evidence of sepsis, intravascular coagulation and a high risk of developing multiorgan failure. Thirteen patients received 3000 units of antithrombin III (Kybernin P; Behringwerke), followed by a further 1000 units every 6 h. Antithrombin III activity increased from 0.26 +/- 0.04 SE U/ml to 0.82 +/- 0.07 U/ml at 3 h post infusion (normal range 0.80-1.20 U/ml) and remained greater than 0.80 U/ml throughout the study without any apparent increase in the frequency of bleeding. However, survival was not improved and markers of intravascular coagulation remained similar between the two groups. Thus, although the antithrombin III deficiency in fulminant hepatic failure can be corrected by supplementation with antithrombin III concentrate, its use in the prevention of intravascular coagulation and to avoid microvessel plugging needs to be studied at an earlier stage in the disease.
Natural history of AIDS related sclerosing cholangitis: a study of 20 cases.
A case control study of AIDS related sclerosing cholangitis indicates that it has no overall influence on prognosis, but is responsible for a striking reversal of the usual inverse correlation of age and survival in HIV infection. Pain, the principal symptom, was controlled in surviving patients with analgesics alone. Twenty consecutive patients with AIDS related sclerosing cholangitis, defined from at least two characteristic lesions at endoscopic retrograde cholangiopancreatography, were followed for a minimum of 10 months or until death. Median age was 33.5 years (range 27-50). All had abdominal pain; 11 had diarrhoea. Alkaline phosphatase was > 2X normal in 13, but the bilirubin was raised in only three. The median CD4 was 0.024 x 10(9)/l (0.005-0.341). Thirteen had cryptosporidiosis, six had active cytomegalovirus, five had no gastrointestinal pathogen. Three patients are alive without AIDS related sclerosing cholangitis symptoms at 10, 11, and 21 months. Seventeen have died at median 7 (1-23) months. Cytomegalovirus therapy had no apparent influence. The initial CD4 was < 0.11 in all those dying within six months, but correlation of CD4 with prognosis was otherwise poor. Controls, matched for age, CD4, and opportunistic infections had virtually identical overall outcome (median survival 7.5 months) and the expected worse prognosis with increasing age. Increasing age, however, appeared protective in AIDS related sclerosing cholangitis (r = +0.6; p < 0.05): this is not explained by disproportionate degrees of immunosuppression, nor by opportunistic infections.
Parenteral nutrition in adult intensive care.
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Differences in the acute and chronic antihypertensive effects of lisinopril and enalapril assessed by ambulatory blood pressure monitoring.
Although lisinopril and enalapril are equipotent angiotensin converting enzyme (ACE) inhibitors lisinopril has been reported to produce greater inhibition of plasma ACE 24 hours after single doses. This study compared the antihypertensive effects of once daily 10mg doses of the drugs using a randomised, double-blind, two period cross-over design with ambulatory blood pressure monitoring. Lisinopril lowered mean 24 hour systolic blood pressure significantly more than enalapril after 4 weeks of treatment (14/7 +/- 2/1mmHg & 9/6 +/- 2/1mmHg, respectively, adjusted SBP difference 4.8mmHg, P < 0.01). This difference was confined to the second 12 hours of the daily dosage interval (adjusted SBP difference 13-24 hours after dosing 9.9mmHg, P < 0.001). The diastolic pressure showed a similar trend but this was not statistically significant. The side effects of each agent were minor. We conclude that chronic, once daily therapy with 10mg of lisinopril reduces systolic blood pressure more effectively than an equal dose of enalapril due to its greater effect in the latter half of the 24 hour dosage interval.
Hormonal treatment of hepatocellular carcinoma.
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Clonidine in the treatment of alcohol withdrawal in the intensive care unit.
We present two cases of patients with a past history of alcohol abuse admitted to the Intensive Care Unit (ICU) for treatment of respiratory problems, after multiple trauma and after sub-total colectomy, respectively. In both patients, features of alcohol withdrawal were prominent after sedation had been discontinued. Both were treated successfully with an infusion of clonidine.
Lipomatosis of the ileocaecal valve simulating Crohn's disease.
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Diagnosis of Pneumocystis carinii pneumonia in HIV antibody positive patients by simple outpatient assessments.
BACKGROUND: As increasing numbers of patients with immunosuppression induced by the human immunodeficiency virus (HIV) present with respiratory symptoms it is important to differentiate Pneumocystis carinii pneumonia from other chest diseases rapidly and start treatment early. The management of pneumocystis pneumonia could be improved if clinicians could diagnose this condition confidently on the basis of simple clinical assessments. METHODS: Three hundred and eighteen patients with evidence of immunosuppression due to HIV infection and suspected pneumocystis pneumonia were investigated. A clinical history was taken and arterial blood gas analysis, chest radiography, oximetry during exercise, and sputum induction or bronchoscopy (or both) were performed. RESULTS: Pneumocystis pneumonia was confirmed microscopically from induced sputum or bronchoalveolar lavage fluid in 154 patients; 118 had other chest disease. The remaining 46 patients had no definitive diagnosis. The best single independent predictors of a diagnosis of pneumocystis pneumonia were exercise induced oxygen desaturation and obvious interstitial infiltrates on the chest radiograph (odds ratios of 4.88 and 5.44 respectively). The symptom triad of exertional dyspnoea, cough, and fevers; the absence of pneumocystis pneumonia prophylaxis; and resting arterial hypoxaemia were less predictive (odds ratio 2.07, 3.72, and 0.69). An algorithm was developed that gave a positive predictive value for confirmed pneumocystis pneumonia of 95% and also identified those patients with a very small chance of having pneumocystis pneumonia (negative predictive value 85%). CONCLUSIONS: The diagnosis of an initial episode of pneumocystis pneumonia can be confidently made in a large proportion of immunosuppressed patients with respiratory symptoms on the basis of clinical symptoms, the absence of prophylaxis, chest radiographic appearances, and oxygen desaturation during exercise as shown by oximetry. Using these simple features clinicians can rapidly assign patients to the appropriate type of management at presentation.