Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group

PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques. MATERIALS AND METHODS: A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant). CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.     

Determination of Hounsfield value for CT-based design of custom femoral stems

Ct and advanced computer-aided design techniques offer the means for designing customised femoral stems. Our aim was to determine the Hounsfield (HU) value of the bone at the corticocancellous interface, as part of the criteria for the design algorithm. We obtained transverse CT images from eight human cadaver femora. The proximal femoral canal was rasped until contact with dense cortical bone was achieved. The femora were cut into several sections corresponding to the slice positions of the CT images. After obtaining a computerised image of the anatomical sections using a scanner, the inner cortical contour was outlined and transferred to the corresponding CT image. The pixels beneath this contour represent the CT density of the bone remaining after surgical rasping. Contours were generated automatically at nine HU levels from 300 to 1100 and the mean distance between the transferred contour and each of the HU-generated contours was computed. The contour generated along the 600-HU pixels was closest to the inner cortical contour of the rasped femur and therefore 600 HU seem to be the CT density of the corticocancellous interface in the proximal part of cadaver femora. Generally, femoral bone with a CT density beyond 600 HU is not removable by conventional reamers. Thus, we recommend the 600 HU threshold as one of several criteria for the design of custom femoral implants from CT data.     

Incidence of breast cancer in a Norwegian cohort of women with potential workplace exposure to 50 Hz magnetic fields.

BACKGROUND: The risk of breast cancer was investigated in a large dynamic population-based cohort of all 1.1 million economically active women in Norway with potential exposure to 50 Hz magnetic fields at the censuses of 1960, 1970, and 1980. METHODS: The follow-up period for the cohort was 1961-1992. For each woman, date of birth and census information on occupation and socioeconomic status were ascertained. These data were linked to the breast cancer morbidity information in the Cancer Registry of Norway. Exposure to magnetic fields was assessed a priori using two different approaches. In the first approach, hours per week in a potential magnetic field above background level (0.1 microT) were classified by an expert panel. In the second approach, measured magnetic fields from a separate study of men at work were allocated to the women's census job titles. In both approaches, exposure was cumulated over the years of employment (work hours and microT-years, respectively). RESULTS: The Poisson regression analysis showed a risk ratio (RR) of 1.14 (95% confidence interval (CI) = 1.10-1.19) in the highest exposure category compared to the lowest when using the first approach, and the corresponding RR was 1.08 (95% CI = 1.01-1.16) when using the second approach. For women younger than 50 years, RR was 1.20 (95% CI = 1.11-1.29) and 1.12 (95% CI = 0.98-1.28), respectively. CONCLUSIONS: The results give some support to the hypothesis that exposure to 50 Hz magnetic fields may increase the risk of breast cancer. However, since no direct information on exposure was available, no firm conclusions can be drawn.     

Effects of doxazosin and atenolol on circulating endothelin-1 and von Willebrand factor in hypertensive middle-aged men.

Elevated levels of endothelin-1 (ET-1) and von Willebrand factor (vWF), both markers indicative of endothelial function, are associated with hypertension. In a randomized open study we investigated the effect of antihypertensive treatment with the alpha-blocker doxazosin (n = 23) or the beta-blocker atenolol (n = 22) for 22 weeks on circulating levels of ET-1 and vWF in middle-aged men with essential hypertension. Blood pressure reduction was satisfactorily achieved with both drugs, although the decrease in the atenolol group was larger than that in the doxazosin group. A reduction in the levels of vWF occurred in both groups, being more pronounced in the alpha-blocker group compared with the decrease on beta blockers, p = 0.004 and p = 0.056, respectively. In the alpha-blocker group, there was a significant correlation (r = 0.50, p = 0.022) between the reduction in diastolic blood pressure and the decline in vWF. A highly significant decrease in plasma ET-1 was obtained during beta blockade (p = 0.007), whereas no significant change occurred within the alpha-blocker group. There was, however, no correlation between the decrease in blood pressure and the reduction in ET-1. The different favorable effects of alpha and beta blockers on endothelial function expressed as vWF and ET-1, could indicate that the effects are probably related not only to the blood pressure per se, but also to the different pharmacologic mechanisms of the drugs.     

Acyclovir treatment of relapsing-remitting multiple sclerosis

Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on intent-to-treat data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0–2), medium (3–5) and high (6–8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.     

Potentials of local health surveys: a state-of-the-art summary.

This paper provides a state-of-the-art summary of the potentials and limitations of local surveys for assessing health problems in local areas. The information they provide may be helpful for a variety of purposes such as measuring the need for services, planning programs to address these needs, and evaluating their impact. Particular advantages of surveys are that they: provide information on the needs of people who have not sought care; permit special studies of particular target groups; provide data on variables which are only available from "asking" people; enable information to be collected on a range of correlates and indicators of health care behavior; provide an opportunity for examining relationships among variables; and permit well-timed community estimates of the impact of experimental programs. Limitations include the validity and reliability of survey data, and the costs and other problems of survey implementation.     

Fibromuscular dysplasia of the internal carotid arteries

Seven patients with fibromuscular dysplasia of the internal carotid arteries have been operated upon at Walter Reed Army Medical Center. One lesion was treated by graduated dilatation with Bake's dilators combined with resection, end-to-end anastomosis, and vein patching of a tortuous segment. All other lesions were treated by graduated dilatation with an arterial dilator-shunt. All of these patients are asymptomatic presently. One patient has been operated upon recently because of symptoms related to the previously unoperated side as well as mild symptoms related to the previous operation. Two other patients with arteriographic evidence of fibromuscular dysplasia are being followed clinically. One is asymptomatic and one has minimal symptoms. Both are being treated with acetylsalicylic acid in hopes of preventing microembolization from these lesions. Important technical considerations in treating this condition are meticulous dissection of the internal carotid artery as near to the base of the skull as possible, confining the arteriotomy to the region of the carotid bulb, and straightening the carotid artery while passing the dilator under direct vision. A technique for routine shunting in these patients now is available.     

Characterization of and drug influence on a calmodulinsensitive phosphodiesterase purified from bovine brain

A calmodulin-sensitive phosphodiesterase was purified from bovine brain. The purification procedure involved ammonium sulphate fractionation, two chromatographic steps on DEAE-cellulose, gel-filtration on Sephadex G-200, and finally one DEAE-cellulose run, and gave a 2300-fold purification. The purified phosphodiesterase had a Vmax for cyclic AMP of 126 mumol/mg protein X min. and was activated 8-fold by addition of calmodulin and calcium. According to SDS-electrophoresis the purified enzyme contained one major peptide of 59,000 daltons, but the preparation was not homogeneous. The enzyme was characterized kinetically and with regard to the effect of cations, pH temperature, and nucleotides. Furthermore, the influence in vitro on enzyme activity of several classes of drugs, e.g. antidepressants, neuroleptics, antiallergics, platelet inhibitors, and some "reference phosphodiesterase inhibitors" was investigated.