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.     

Degradation of extracellular matrix proteins (fibronectin, vitronectin and laminin) by serine-proteinases isolated from Lonomia achelous caterpillar hemolymph.

Lonomia achelous is a caterpillar distributed in southern Venezuela and in northern Brazil that causes an acute hemorrhagic syndrome in people who have contact with its bristles. The effect of the crude hemolymph and its chromatographic fractions (FDII, Lonomin V and Lonomin V-2) on extracellular matrix proteins was studied. The chromatographic fractions show activities similar to plasmin and urokinase. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both lonomins appear as a protein band of 25 kDa under reduced conditions. By exclusion chromatography, the molecular weights of Lonomin V and Lonomin V-2 were 26.5 and 24.5 kDa, respectively. Fibronectin, laminin and vitronectin were degraded by all venom components. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under reduced conditions, shows that lonomins degrade fibronectin in four main fragments of 116, 60, 50 and 30 kDa. Molecular exclusion chromatography in native conditions shows that the molecular masses of these fragments are > or = 300, 62 and 27 kDa. The proteolytic effect of lonomins was abolished by benzamidine/HCl, iodoacetic acid and aprotinin. The extracellular matrix protein degradation together with the fibrino(geno)lytic activity of hemolymph and its fractions could explain, in part, the hemorrhagic syndrome, and the wound dehiscence in persons who have had contact with the L. achelous caterpillar.     

Incontinentia pigmenti: MR demonstration of brain changes.

PURPOSETo describe the MR findings in eight girls and women with incontinentia pigmenti, from two families. Four had skin lesions and neurologic disease, and four had only skin lesions.METHODSEight patients had physical examination, family history, electroencephalogram and MR examination of the brain. MR was repeated in the two cases with more severe changes several years after the first study.RESULTSMR revealed brain changes only in the four patients who had neurologic disease associated with the cutaneous lesions of incontinentia pigmenti. Abnormalities were located in the cerebral hemisphere contralateral to the most affected side of the body. In two cases, the MR changes were subjacent to the scalp areas where the most severe cutaneous lesions were located in the neonatal period. Hypoplasia of the corpus callosum, probably secondary to atrophy of one or both cerebral hemispheres, and abnormal signal and atrophy of the lateral regions of one of the cerebellar hemispheres also were found in all four cases. Although the changes were seen in both the T1- and T2-weighted images, they were most evident in the latter. The four patients in the fourth stage who had only cutaneous lesions without neurologic problems did not reveal any MR abnormalities.CONCLUSIONSThis study demonstrates MR signal changes and focal atrophy of the cerebrum, cerebellum, and corpus callosum in patients with incontinentia pigmenti and neurologic disorders. The MR images appear normal in patients with incontinentia pigmenti who have no neurologic abnormalities.     

Cognitive profiles of individual patients with Parkinson's disease and dementia: comparison with dementia with lewy bodies and Alzheimer's disease.

We describe the pattern of cognitive profiles within a community-based sample of patients with Parkinson's disease (PD) and dementia (PDD) using cluster analyses, and compare the results with data from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Fifty patients with PDD and 39 with AD from Stavanger, Norway, and 62 patients with DLB from San Diego, CA, USA were diagnosed by either standardized clinical procedures or criteria (all PDD and all AD cases) or necropsy (all DLB cases). Four subgroups were identified: two subgroups with a subcortical cognitive profile (one with mild and one with moderate dementia severity), one subgroup with global impairment and severe dementia, and one subgroup with a cortical cognitive profile and moderate dementia. Of the patients with PDD and with DLB, 56% and 55%, respectively, had a subcortical cognitive profile, compared with only 33% of the AD patients. Conversely, 30% of the patients with PDD and 26% of those with DLB had a cortical cognitive profile, compared with 67% of the patients with AD. These findings suggest that in some patients with PDD, frontosubcortical changes are the main contributing factor to dementia, whereas in other patients, cortical and hippocampal changes are more important.     

Motor neuron disease and optic neuropathy after acute exposure to a methanol-containing solvent mixture.

A 34-years-old floor-layer developed optic neuropathy and motor neuron disease after being accidentally exposed to a solvent mixture containing methanol and other substances. Optic neuropathy is a complication of methanol poisoning, but the onset of a motor neuron disorder resembling amyotrophic lateral sclerosis after the exposure to these substances has not been previously described. The temporal onset of the clinical symptoms, biological plausibility, young age of the patient and absence of neurological disorders in the family history raises suspicion of a possible causative relationship.     

Molecular Interaction of Droperidol with Human Ether-a-go-go-related Gene Channels: Prolongation of Action Potential Duration without Inducing Early Afterdepolarization

Background: The cardiac safety of droperidol given at antiemetic doses is a matter of debate. Although droperidol potently inhibits human ether-a-go-go-related gene (HERG) channels, the molecular mode of this interaction is unknown. The role of amino acid residues typically mediating high-affinity block of HERG channels is unclear. It is furthermore unresolved whether droperidol at antiemetic concentrations induces action potential prolongation and arrhythmogenic early afterdepolarizations in cardiac myocytes.

Methods: Molecular mechanisms of HERG current inhibition by droperidol were established using two-electrode voltage clamp recordings of Xenopus laevis oocytes expressing wild-type and mutant channels. The mutants T623A, S624A, V625A, Y652A, and F656A were generated by site-directed mutagenesis. The effect of droperidol on action potentials was investigated in cardiac myocytes isolated from guinea pig hearts using the patch clamp technique.

Results: Droperidol inhibited currents through HERG wild-type channels with a concentration of half-maximal inhibition of 0.6-0.9 [mu]m. Droperidol shifted the channel activation and the steady state inactivation toward negative potentials while channel deactivation was not affected. Current inhibition increased with membrane potential and with increasing duration of current activation. Inhibition of HERG channels was similarly reduced by all mutations. Droperidol at concentrations between 5 and 100 nm prolonged whereas concentrations greater than 300 nm shortened action potentials. Early afterdepolarizations were not observed.     

Radiculopathy following intrathecal baclofen pump implantation]

INTRODUCTION: Intrathecally delivered baclofen has been used as a treatment for severe spasticity since 1984. After a successful intrathecal baclofen trial, a programmable drug delivery system was implanted. Few early complications such as infection or hematoma are observed after this surgery. OBJECTIVE: To describe an unusual and unknown complication of intrathecal baclofen therapy. METHOD: We report 2 cases of complications of intrathecal baclofen therapy, radiculalgy, that appeared early after pump implantation. The clinical symptoms and computed tomography (CT) results are described. RESULTS: The first patient described pain, which evoked left S1 radiculopathic features. The second had left L5 radiculopathic involvement. The mean pain level was estimated on a 10-point visual analog scale as 7.5 (range 4-9). Lumbar CT scan showed a conflict between the symptomatic root and the catheter and eliminated other causes of the symptoms. Treatment with analgesic drugs was successful in 1 patient. The other presented with proximal disconnection of the catheter, which led to surgical replacement of the catheter. The pain disappeared after this surgery. CONCLUSION: Intrathecal baclofen therapy with a subcutaneously implanted progammable pump can be complicated by radiculalgy secondary to a conflict between the catheter and symptomatic root. The diagnosis is made by CT lumbar scan. If medical treatment is not sufficient, surgery could be proposed to replace the catheter.     

Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.