Neuroprotective properties of valproate

Neuropsychiatric disturbances are extremely common in Alzheimer’s disease (AD), and represent integral features of the illness, as well as appropriate targets for therapy. We are interested in designing trials aimed at preventing or delaying the emergence of psychopathology in AD. For symptomatic treatment of agitation, mood stabilizers, particularly sodium valproate, have proved to be beneficial in some patients. Since these effects take several weeks to emerge, we considered that they might be dependent on potentially neuroprotective actions of valproate, such as inhibition of apoptosis and slowing of neurofibrillary tangle formation. In this article we present the rationale for testing the neuroprotective potential of valproate experimentally in mouse models of tauopathy and in a clinical trial of patients with AD who lack psychopathology at baseline. Together, these studies will provide important tests of the hypothesis that valproate, either through inhibition of tau phosphorylation or some other mechanism, is a useful therapeutic agent to modify disease progression in AD.     

Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

A self-reported survey of Alzheimer's centers in Southwestern Pennsylvania

Directors of nursing at 23 nursing homes with Alzheimer's units in Southwestern Pennsylvania completed a self‐reported survey of 12 questions. Responses from the self‐administered questionnaires (100% response rate) revealed a wide variation in the staff categories assessing the oral health status of newly admitted residents with AD. The respondents described oral examinations that were incomplete when compared to the oral indicators listed in the Minimum Data Set. All nursing homes reported that oral hygiene was provided each day. The number of residents in a facility had a significant effect on the frequency of oral hygiene provided. Only 52% of the facilities reported yearly oral examinations for this population. According to the respondents, dental treatment was typically performed on‐site. The oral health care costs were paid by Medicare, Medicaid, the residents/family members, or by other undescribed resources. Insufficient time, staff, and training, as well as uncooperative behavior, were identified as barriers to optimum oral health care for residents with AD. Additional staff, specialized training, and increased government reimbursement were suggested to improve the oral health care for this group of older adults. For future studies, review of medical records and on‐site evaluation of the oral health care at these facilities should be required to verify the reported practices.     

Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

Abstract   We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15–2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.     

A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R−) solid organ transplant recipients

Abstract:  Long-term prophylaxis against cytomegalovirus (CMV) started immediately after transplantation in (D+/R−) poses a higher risk of late-onset CMV disease. Delayed CMV prophylaxis could allow a transitory exposure of the immune system to CMV, which would let the immune system mount an adequate CMV-specific cytotoxic response in (D+/R−) patients and confer protection against CMV disease. We included all (D+/R−) solid organ transplant recipients (SOT) performed at our institution (January 3/October 6) who received CMV prophylaxis (mainly with oral valganciclovir) during 100 d. In the first period (until December 4), prophylaxis was initiated immediately after transplantation (conventional prophylaxis: CP). Since January 5, it was initiated after 14 d (delayed prophylaxis: DP). Incidence and severity of CMV disease was compared between both groups. A total of 44 SOT recipients were included (CP: 26 and DP: 18). CMV disease was diagnosed in eight patients (18%), seven of 26 (27%) in the CP group, and one of 18 (5.5%) in the DP group (p = 0.07). CMV colitis was reported in five of 26 patients in the CP group (19%), whereas there were no cases of visceral CMV disease in the DP group (p = 0.048). A 14-d delay in the beginning of long-term prophylaxis against CMV in (D+/R−) is safe and could prevent the onset of late-CMV disease.     

100例性病患者心理健康状况调查分析

目的：探讨性病患者的心理健康状况,为临床治疗和护理提供依据。方法：采用症状自评量表（SCL-90）对100例性病患者的心理健康状况进行测验。结果：100例性病患者SCL-90检测的阳性率为51%,阳性样本因子分居前的是敌对、强迫症状、抑郁、人际敏感。结论：性病患者广泛存在的心理问题,在药用治疗的同时应注意心理方面的治疗和疏导。     

An unusual cause of adult onset cerebellar ataxia with hypogonadism

We report an unusual case of sporadic adult onset cerebellar ataxia with hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and dysarthria along with complaints of non-development of secondary sexual characteristics and erectile dysfunction. There were complaints of intermittent diarrhea. Clinical examination revealed a pan-cerebellar syndrome with features of hypoandrogenism. No eye movement abnormalities were evident. There were signs of malabsorption. Investigations confirmed the presence of auto-antibodies found in celiac disease, and a duodenal biopsy confirmed the same. Hypoandrogenism was postulated to be due to hypergonadotropic hypogonadism which has been mentioned in a few patients of celiac disease. However, the pattern seen in our patient was of a hypogonadotropic hypogonadism. This is probably secondary to an autoimmune hypophysitis seen in some patients in the absence of other clinical manifestations. Autoantibody testing should be a diagnostic necessity in any adult with a sporadic cerebellar ataxia.     

Castleman disease: surgical cure in pediatric patients

Castleman disease is a rare disorder characterized by lymphoid hyperplasia which rarely manifests in children. We present 2 cases which highlight both histologic variants of this disease, and provide suggestions regarding workup and treatment with the goal of making practitioners aware of Castleman disease in the differential diagnosis of a child presenting with vague symptoms.