Intrathecal vincristine: a fatal chemotherapeutic error with devastating central nervous system effects

Summary The devastating neuropathological changes wrought by the intrathecal administration of vincristine are reported, with a detailed account of the widespread lesions in the brain and spinal cord, found in post-mortem light- and electron-microscope studies.     

Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.     

A double blind trial of sex drive reducing medication in pedophiles

A sample of 100 men accused of sexual assault on a child and referred to a forensic clinic were approached for assessment and treatment in a double blind study of MPA (Provera). A total of 48 men completed assessment and 18 agreed to participate in the drug trial. Only 11 completed a 3-month course of MPA or placebo therapy. Those refusing treatment were less intelligent and less impaired on the Luria-Nebraska Neuropsychological Test Battery but were more impaired on the Halstead-Reitan Neuropsychological Test Battery. Dropouts differed only in reporting more frequent sexual fantasies of children. Of a possible 27 side effects for MPA, only two were statistically significant. MPA led to more depression and excess salivation than did the placebo, although the frequency of fatigue was noteworthy. MPA appeared as a useful sex drive reducing medication with few side effects but compliance in taking the drug was seen as a major obstacle in its use with pedophiles.     

The impact of a policy of collaborative management on mortality and morbidity from infective endocarditis

The present study represents a comprehensive retrospective review of endocarditis in a large district general hospital since the inception of a formalized policy involving collaborative management a decade ago. The principle was to involve a recognised team of cardiologists, specialists in infectious disease and microbiologists in the treatment of the disease from the moment of its diagnosis. The pattern of infection has not altered in terms of prevalent organisms and valves infected since the change in management policy. There has, however, been a significant decline in the mortality, from 34 to 24% for all patients with endocarditis. Amongst those referred for collaborative management, the mortality has fallen to 6%. The single greatest improvement is a reduction in the number of patients dying of heart failure, the number of patients developing systemic emboli or requiring prosthetic valve replacement remaining unchanged. The results indicate that early referral to, and treatment by, a multidisciplinary team can significantly reduce the mortality from bacterial endocarditis.     

Effect of a gonadotropin releasing hormone analog on cerebral hemodynamics in premenopausal women.

BACKGROUND: Impaired reactivity of cerebral blood vessels is associated with increased risk of stroke. Female sex hormones have vasoactive effects in a number of vascular beds but their effects upon the cerebral circulation are not well understood. Ultrasound techniques allow us to examine the ability of intracranial vessels to dilate in response to a pharmacological stimulus (the carbonic anhydrase inhibitor acetazolamide). We studied intracranial hemodynamics in a group of premenopausal women before and after induction of a temporary hypoestrogenic state. METHODS: We examined middle cerebral artery mean flow velocity, common and internal carotid artery pulsatility index and cerebrovascular reactivity to acetazolamide (CVR) in a group of women undergoing treatment for menstrual disorders. Volunteers underwent ultrasound examination during the follicular phase of the menstrual cycle and after completing treatment with gonadotropin releasing hormone (GnRH, goserelin 3.6 mg) administered subcutaneously every 28 days for 12 weeks. The study was conducted in a prospective, single-blind fashion and analyzed using parametric comparisons of means to examine change in intracranial hemodynamic parameters between pre- and postmenopausal states. RESULTS: Twelve premenopausal women aged 37.2+/-7 years and without overt vascular disease completed the protocol. GnRH reduced serum estrogen concentration (215.6+/-122 pg/ml vs. 82.4+/-12 pg/ml, p=0.0047) but this was not associated with a change in CVR (145+/-19% and 146+/-14% for follicular and post-GnRH studies, respectively (p=0.6). No significant changes in blood pressure, internal carotid or middle cerebral artery pulsatility or mean flow velocity were observed between time points. CONCLUSION: Neither resting cerebral hemodynamics nor reactivity of cerebral resistance vessels to a potent vasodilatory stimulus changed when the circulating concentration of estradiol was artificially decreased using a GnRH agonist. Induction of a hypoestrogenic state does not appear to influence cerebral vasodilatory capacity in the short term.     

Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. cohort.

BACKGROUND: 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Long-duration statin use was associated with substantially reduced risk of advanced prostate cancer in a recent large prospective study. METHODS: We examined the association between use of cholesterol-lowering drugs and prostate cancer incidence by disease stage and grade among 55,454 men in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate RRs. RESULTS: During follow-up from 1997 to 2003, we identified 3,413 cases of incident prostate cancer, including 317 cases of advanced prostate cancer. After adjustment for age, history of prostate-specific antigen testing, and other potential prostate cancer risk factors, current use of cholesterol-lowering drugs for 5 or more years was not associated with overall prostate cancer incidence (multivariate adjusted rate ratio, 1.06; 95% confidence interval, 0.93-1.20), but was associated with a marginally statistically significant reduction in risk of advanced prostate cancer (rate ratio, 0.60; 95% confidence interval, 0.36-1.00). CONCLUSION: These results provide some support for the hypothesis that long-term statin use is associated with reduced risk of advanced prostate cancer.     

The association of lichen planus of the penis with squamous cell carcinoma in situ and with verrucous squamous carcinoma

Two cases of squamous cell carcinoma (SCC) of the penis, one verrucous type and one in situ, arising in association with an inflammatory dermatosis most consistent with lichen planus, are described. Although SCC has previously been reported to have arisen from lichen planus of the oral mucosa, these are the first reported cases of the coexistence of these processes on the penis.