Low-voltage direct current as a fungicidal agent for treating onychomycosis

Onychomycosis, most commonly caused by two species of dermatophyte fungi--Trichophyton rubrum and Trichophyton mentagrophytes--is primarily treated with regimens of topical and systemic antifungal medications. This study was undertaken to evaluate in vitro the efficacy of low-voltage direct current as an antifungal agent for treating onychomycosis. Agar plate cultures of T rubrum and T mentagrophytes were subjected to low-voltage direct current electrostimulation, and antifungal effects were observed as zones in the agar around the electrodes lacking fungal growth. Zones devoid of fungal growth were observed for T rubrum and T mentagrophytes around anodes and cathodes in a dose-dependent manner in the current range of 500 microA to 3 mA. Low-voltage direct current electrostimulation has great clinical potential for the treatment of onychomycosis and perhaps other superficial maladies of fungal etiology.     

Measuring underuse of necessary care among elderly Medicare beneficiaries using inpatient and outpatient claims

CONTEXT: Continuing changes in the health care delivery system make it essential to monitor underuse of needed care, even for relatively well-insured populations. Traditional approaches to measuring underuse have relied on patient surveys and chart reviews, which are expensive, or simple single-condition claims-based indicators, which are not clinically convincing. OBJECTIVE: To develop a comprehensive, low-cost system for measuring underuse of necessary care among elderly patients using inpatient and outpatient Medicare claims. DESIGN: A 7-member, multispecialty expert physician panel was assembled and used a modified Delphi method to develop clinically detailed underuse indicators likely to be associated with avoidable poor outcomes for 15 common acute and chronic medical and surgical conditions. An automated system was developed to calculate the indicators using administrative data. SETTING AND SUBJECTS: A total of 345,253 randomly selected elderly US Medicare beneficiaries in 1994-1996. MAIN OUTCOME MEASURES: Proportion of beneficiaries receiving care, stratified by indicators of necessary care (n = 40, including 3 for preventive care), and avoidable outcomes (n = 6). RESULTS: For 16 of 40 necessary care indicators (including preventive care indicators), beneficiaries received the indicated care less than two thirds of the time. Of all indicators, African Americans scored significantly worse than whites on 16 and better on 2; residents of poverty areas scored significantly lower than nonresidents on 17 and higher on 1; residents of federally defined Health Professional Shortage Areas scored significantly lower than nonresidents on 16 and higher on none (P<.05 for all). CONCLUSIONS: This claims-based method detected substantial underuse problems likely to result in negative outcomes in elderly populations. Significantly more underuse problems were detected in populations known to receive less-than-average medical care. The method can serve as a reliable, valid tool for monitoring trends in underuse of needed care for older patients and for comparing care across health care plans and geographic areas based on claims data. JAMA. 2000;284:2325-2333.     

Association of COMT Val158Met genotype with executive functioning following traumatic brain injury

Catechol-O-methyltransferase (COMT) is thought to functionally modulate dopamine neurons, thus likely influencing frontal-executive functioning. High enzyme activity (COMT Val) and low enzyme activity (COMT Met) are functional polymorphisms resulting from a G to A transition in exon 4 (codon 158) of the human COMT gene. Decreased cortical dopamine should result in poorer executive functioning. Therefore, the authors hypothesized that individuals with traumatic brain injury (TBI) and the low enzyme activity polymorphism would perform better on tests of executive functioning than individuals with the high enzyme activity polymorphism. One hundred thirteen individuals referred to the Defense and Veterans Brain Injury Center underwent a comprehensive TBI evaluation and were genotyped for the COMT polymorphism. Comparison of mean differences among the COMT genotype groups for several measures of aspects of executive functioning was conducted using analysis of variance (ANOVA) with adjustment for multiple comparisons. Homozygotes for the higher activity allele made more perseverative responses on the Wisconsin Card Sorting Test, while homozygotes for the lower activity allele had the least number of perseverative responses. While it cannot be determined whether TBI influenced the association of COMT Val158Met to executive functioning, these data extend the known relationship of genotype to executive performance seen in healthy comparison subjects and individuals with schizophrenia to individuals with TBI.     

Erectile function, incontinence, and other quality of life outcomes following proton therapy for prostate cancer in men 60 years old and younger

BACKGROUND:

This study sought to evaluate patient‐reported health‐related quality of life following proton therapy for prostate cancer in men ≤60 years old.

METHODS:

Between August 2006 and January 2010, 262 hormone‐naive men ≤60 years old were treated with definitive proton therapy for prostate cancer. Before treatment and every 6 months after treatment, patients filled out the Expanded Prostate Index Composite (EPIC) and the International Index of Erectile Function (IIEF) questionnaires. Potency was defined as successful sexual intercourse in the prior month or an EPIC sexual summary (SS) score ≥60.

RESULTS:

Median follow‐up was 24 months; 90% of men completed follow‐up EPIC forms within the last year. For EPIC urinary, bowel, and hormone subscales, the average decline from baseline to 2 years was ≤5 points, except for bowel function (5.2 points). SS scores declined 12.6 points after 2 years. Potency rates declined by 11% from baseline at 2 years, but 94% of men were potent with a baseline IIEF > 21, body mass index < 30, and no history of diabetes. At 2 years after treatment, only 1.8% of men required a pad for urge incontinence. On multivariate analysis, factors associated with a significant decline in SS score were mean penile bulb dose ≥40 cobalt Gy equivalents (P = .012) and radiation dose ≥80 cobalt Gy equivalents (P = .017); only diabetes was significantly associated with impotence (P = .015).

CONCLUSIONS:

Young men undergoing proton therapy for treatment of prostate cancer have excellent outcomes with respect to erectile dysfunction, urinary incontinence, and other health‐related quality of life parameters during the first 2 years after treatment. Longer follow‐up is needed to confirm these findings. Cancer 2012. © 2012 American Cancer Society.     

Distal myasthenia gravis: case report

We report the case of a 30-year-old woman with a 7-year history of distal lower limbs weakness that evolved to upper limbs weakness. On neurological examination, she presented normal cranial nerves, bilateral quadriceps and feet interosseous atrophy, normal muscular tonus, muscular weakness more severe in dorsal feet interosseous and anterior tibial, and decreased deep tendon reflexes. Repetitive nerve stimulation of the ulnar and fibular nerves showed a decrement greater than 10% of the compound muscle action potential. Antibody against acetylcholine receptor titer was positive. Computed tomography scan of the thorax was normal. Thyroid function tests showed evidence of hyperthyroidism. Distal muscular weakness is a rare onset presentation of myasthenia gravis. However, myasthenia gravis must be considered in the differential diagnosis of distal limb weakness.     

Driving performance during word generation--testing the function of human brain lateralization using fTCD in an ecologically relevant context

It has been hypothesized that cerebral lateralization of function enhances cognitive performance. Evidence was found in birds and fish. However, recent research in humans did not support this hypothesis. We aimed to replicate and extend these findings for single- and dual-task performance in an ecologically relevant task. We combined a word generation task which is assumed to be primarily processed in the left hemisphere with a driving task which is assumed to be primarily processed in the right hemisphere. For each task the individual strength and direction of hemispheric lateralization was assessed by using functional transcranial Doppler sonography (fTCD). For each subject (36 right-handed, 35 nonright-handed) performance was measured in the two single-tasks and in the dual-task condition. On average, subjects showed a left hemisphere bias for the word generation task, a right hemisphere bias for the driving task and dual-task interference. Within subjects, lateralization of language and driving were statistically independent.In accordance with earlier studies, the results show no indication of a positive effect of strength of lateralization on performance in single-tasks or dual-task efficiency. We also found no advantage of a typical compared to an atypical or a contralateral compared to an ipsilateral lateralization pattern. In right-handers, but not in nonright-handers, we even found a negative relationship between strength of lateralization and dual-task efficiency for atypically lateralized subjects. This further supports the suggestion that lateralization does not enhance cognitive performance in humans.     

Divergent effects of putative anxiolytics on stress-induced fos expression in the mesoprefrontal system of the rat

Previously, we reported that R(+)HA-966, a weak partial agonist for the glycine/NMDA receptor, and guanfacine, a noradrenergic alpha2 agonist, have anxiolytic-like actions on the biochemical activation of the mesoprefrontal dopamine neurons and fear-induced behaviors. Here, we examined these two putative anxiolytic agents, both with primary actions independent of GABAergic systems, for their ability to alter stress-induced Fos-like immunoreactivity in the mesoprefrontal cortex and in tyrosine hydroxylase-stained, presumed dopaminergic, neurons in the ventral tegmental area. The benzodiazepine agonist, lorazepam, and partial agonist, bretazenil, were also tested in this footshock paradigm [10 x 0.5 sec, 0.8 mA paired with a 5-sec tone]. In saline-treated rats, footshock resulted in an increase in Fos-li in the prelimbic and infralimbic cortices and tyrosine hydroxylase-labeled cells in the ventral tegmental area. Treatment with lorazepam or bretazenil prevented the stress-induced activation in Fos-li nuclei in all regions of the medial prefrontal cortex and in dopaminergic neurons in the ventral tegmental area. In contrast, the actions of the novel anxiolytic-like agents on stress-induced Fos-li were different than those observed with benzodiazepine agonists. Both putative anxiolytics, R(+)HA-966 and guanfacine, did not reduce, but significantly enhanced the stress-induced Fos-li in the prelimbic region of the medial prefrontal cortex. Additionally, treatment with R(+)HA-966 completely blocked, while guanfacine attenuated, the stress-induced increase in the number of Fos-li, TH-li cells in the ventral tegmental area. These results indicate that the putative anxiolytics, R(+)HA-966 and guanfacine, have actions on the stress-sensitive mesoprefrontal system which appear distinct from those of traditional anxiolytics.     

Neurological manifestations in chronic mountain sickness: the burning feet-burning hands syndrome

OBJECTIVE: To characterise the clinical features and nerve biopsy findings in patients with chronic mountain sickness (CMS) living in the Peruvian Andes, with particular attention to the occurrence of the "burning feet-burning hands" syndrome. METHODS: Symptoms and signs were documented clinically in 10 patients with CMS and compared with those in five healthy subjects all living at 4338 metres altitude. Sural nerve biopsies were obtained from three patients with CMS.The nerve fibre population and endoneurial microvessels were analyzed morphometrically. RESULTS: All patients with CMS experienced burning and tingling paraesthesiae in the distal parts of their limbs. Similar but milder symptoms confined to the feet occurred in four of five controls. Three patients with CMS had a mild sensory neuropathy on examination, controls were clinically normal. Nerve biopsies showed a mild demyelinating neuropathy in all three with a reduction in the unmyelinated axon population in one. The endoneurial blood vessels showed a reduced thickness in the basal laminal zone compared with control values but were otherwise normal. CONCLUSIONS: Apart from well recognised symptoms and signs of CMS, the study has shown that such patients may also exhibit a mild sensory neuropathy. Its relation to the burning feet-burning hands syndrome, which was not confined to the patients but was also found in controls at altitude, is uncertain. The time course and pattern of the centrifugal resolution of the burning paraesthesiae complex on low altitude sojourn of high altitude natives raises the possibility that a mechanism involving altered axonal transport may be involved. The reduced thickness of the basal laminal zone of microvessels implies that adaptive structural changes to hypobaric hypoxia may also occur in peripheral nerve and are similar to those reported in other tissues of high altitude natives.