The practical assessment and management of bladder outflow obstruction

The initial management of bladder outflow obstruction typically related to benign prostatic hyperplasia (BPH) falls to a large extent within the remit of general practice. Referral onwards to secondary care typically arises following the failure to respond to conservative measures or when complications have supervened; the most significant of which is urinary retention. In the hospital setting, anaesthesia, constipation and immobility are the common precipitants. What follows is a practical guide to the management of these situations and provides an overview of the conservative, medical, minimally invasive and surgical treatments available.     

Electrophysiologic effects of d-sotalol in humans

Sotalol is a beta-adrenergic blocking agent that prolongs the duration of the cardiac action potential in humans, without affecting the upstroke velocity of depolarization. The dextrorotatory isomer, d-sotalol, retains these class III effects, but has little beta-blocking activity in vitro. d-Sotalol has not been studied extensively in humans. The electrocardiographic (ECG) and electrophysiologic effects of d- and d,l-sotalol were therefore assessed in a prospective randomized study of 20 patients. Each patient received either d-sotalol (1, 1.5 or 2 mg/kg body weight) or d,l-sotalol (1 mg/kg) by intravenous infusion. The QT and QTc intervals were prolonged and refractoriness increased in the atrium, atrioventricular (AV) node, His-Purkinje system and right ventricle after both d- and d,l-sotalol. After d-sotalol, the increases in both QT and QTc intervals and in atrial and ventricular effective refractory periods were dose dependent. Highly significant linear correlation was demonstrated between the plasma sotalol level and the change in QT (r = 0.86, p = 0.001) and QTc intervals (r = 0.79, p = 0.002), and between the plasma sotalol level and the effective refractory period of the right atrium (r = 0.75, p = 0.005) and ventricle (r = 0.70, p = 0.025). This study confirms that d-sotalol has effects consistent with class III properties. It demonstrates these effects in humans, and suggests that d-sotalol may prove to be a useful antiarrhythmic agent.     

Patients' experience of epilepsy and health care

OBJECTIVE: The aim of this study was to assess the severity of epilepsy and its effect on patients lives, and to describe patients' use of and attitudes to health care. METHOD: A questionnaire was sent to 595 people with epilepsy identified from 14 general practices in north-west Bristol. All patients aged 16 years and over receiving anti-epileptic medication for their epilepsy were included in the study. Areas investigated included severity of epilepsy and its effect on quality of life, anti-epileptic medication and its perceived effect, health care utilization and preferences for health care. RESULTS: Seizure frequency was strongly associated with adverse effects of epilepsy. Attacks of epilepsy were experienced at least monthly by 20.4% (95% confidence intervals (Cl) 17.0-23.7%) of patients, 29.4% (25.4-33.4%) took more than one anti-epileptic drug, 56.1% (50.1-62.2%) reported drug side effects, 74.1% (70.3-77.8%) would prefer to receive all or most of their epilepsy care in a general practice setting, and 69.8% (63.5- 76.2%) would like contact with a primary care-based epilepsy specialist nurse. During the previous year 42.4% (35.9-48.8%) of patients had not seen a doctor about their epilepsy. Of patients who had attended the general practice only 13.4% (9.6-17.2%) had regular arrangements to see their GP about epilepsy. Patients receiving both primary and secondary care had the greatest needs and wants for improved care. CONCLUSIONS: Structured care, including regular appointments, co-ordination of primary and secondary care, and increased monitoring and discussion, may improve the quality of life of people with epilepsy, but requires evaluation.      

Duplications of the alimentary tract. Clinical characteristics, preferred treatment, and associated malformations.

Duplications of the alimentary tract are unusual congenital anomalies that frequently present a diagnostic as well as therapeutic challenge to the surgeon. Because these lesions occur so infrequently, they are often not suspected until encountered intraoperatively. Due to the complicated anatomy and common blood supply shared between the duplication and associated native bowel, appropriate management requires a familiarity with the anatomy and clinical characteristics of this entity. To better define the range of patient characteristics, clinical presentation, and preferred therapy, 20 enteric duplications were reviewed in 17 patients treated at the Children's Hospital Medical Center from 1956 to 1986. Ages of patients ranged from 1 day to 11 years; 60% were less than 2 years of age at initial presentation. Seven duplications in six patients involved alimentary tract structures of foregut derivation (esophagus, stomach, and Parts I and II of duodenum), with a predominance of girls (4 of 6). Most of these patients (67%) presented with moderate to severe acute respiratory distress and a mass present on chest radiograph. In 67% of the patients, the correct diagnosis was established before operation. None required emergency operative intervention. By contrast, 13 duplications in 11 patients were of midgut or hindgut derivation (Parts III and IV of the duodenum, jejunum, ileum, and colon). In this group of patients, 62% of the duplications involved the cecum, 23% involved the ileum, and 16%, the jejunum. Seventy-eight per cent of the patients were boys. The most common symptoms were nausea and vomiting, and the most common sign was a palpable abdominal mass. Emergency operative intervention was required of eight of 11 patients with duplications involving the small bowel and colon. Three patients presented with an intussusception, four with signs and symptoms consistent with acute appendicitis, one with a small bowel obstruction, and two with gastrointestinal hemorrhage due to the presence of ectopic gastric mucosa within the duplication. It was found that two important points must be considered in regard to the management of enteric duplications: (1) the common blood supply shared between the duplication and native bowel must be carefully protected to avoid undue sacrifice of normal bowel, and (2) the presence of heterotopic gastric mucosa in 35% of patients negates internal drainage.(ABSTRACT TRUNCATED AT 400 WORDS)     

Early detection of colorectal cancer by quantitative fluorescence image analysis of exfoliated cells

Early-stage colorectal cancer is potentially curable. In the present study, we applied quantitative fluorescence image analysis (QFIA) cytology to the detection of experimental colorectal cancer in a rodent model. QFIA cytology combines visual cytologic examination with quantitation of DNA content in single exfoliated cells. Cancer was induced by treating 110 rats with subcutaneous 1,2-dimethylhydrazine. Sequential colon washes were obtained weekly from each animal for 20 weeks. Control animals were treated identically except for the administration of carcinogen. Cells that were cytologically abnormal or had increased DNA content were found starting in the second week. By the eighth week, roughly 50 percent of animals had positive results, and this level remained approximately constant for the duration of the study. Tissue pathologic results were normal during weeks 1 to 7. Dysplasias became common during weeks 8 to 15 whereas most cancers appeared during weeks 16 to 21. These results indicate that QFIA cytology is a highly sensitive method for detecting even preneoplastic changes resulting from carcinogen administration and may prove useful in detecting human colorectal cancer.     

Analysis of F1F0-ATPase from Helicobacter pylori.

The adaptive mechanisms that permit Helicobacter species to survive within the gastric mucosa are not well understood. The proton-translocating F1F0-ATPase is an important enzyme for regulating intracellular pH or synthesizing ATP in many other enteric bacteria; therefore, we used degenerate primers derived from conserved bacterial F1F0-ATPase sequences to PCR amplify and clone the gene (atpD) encoding the H. pylori F1F0-ATPase beta subunit. The deduced amino acid sequences of the F1F0-ATPase beta subunits from H. pylori and Wolinella succinogenes were 85% identical (91% similar). To characterize a potential functional role of F1F0-ATPase in H. pylori, H. pylori or Escherichia coli cells were incubated for 60 min in buffered solutions at pH 7, 6, 5, or 4, with or without 100 microM N,N'-dicyclohexylcarbodiimide (DCCD), a specific inhibitor of F1F0-ATPase. At pH 5 and 4, there was no significant decrease in survival of H. pylori in the presence of DCCD compared to its absence, whereas incubation with DCCD at pH 7 and 6 significantly decreased H. pylori survival. E. coli survival was unaffected by DCCD at any pH value tested. We next disrupted the cloned beta-subunit sequence in E. coli by insertion of a kanamycin resistance cassette and sought to construct an isogenic F1F0-ATPase H. pylori mutant by natural transformation and allelic exchange. In multiple transformations of H. pylori cells grown at pH 6 or 7, no kanamycin-resistant F1F0 mutants were isolated, despite consistently successful mutagenesis of other H. pylori genes by using a similar approach and PCR experiments providing evidence for integration of the kanamycin resistance cassette into atpD. The sensitivity of H. pylori to DCCD at pH 7 and 6, and failure to recover F1F0 H. pylori mutants under similar conditions, suggests that the function of this enzyme is required for survival of H. pylori at these pHs.