Vitamin D3 derivatives inhibit the differentiation of Friend erythroleukemia cells

A number of vitamin D3 metabolites inhibit benzodiazepine- and dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells. The inhibition is dose dependent and occurs at nM concentrations. The order of potency of these compounds is 1,25-dihydroxycholecalciferol greater than 1,25,26-trihydroxycholecalciferol greater than 1,24R,25-trihydroxycholecalciferol greater than 1 alpha-hydroxycholecalciferol greater than 24R,25-dihydroxycholecalciferol greater than 25S,26-dihydroxycholecalciferol. The inhibition is maximal when the vitamin D3 analogs are added together with the inducer, and becomes progressively decreased with delayed addition. These results suggest that the vitamin D3 metabolites may play a regulatory role in erythropoiesis.     

Effectiveness of montelukast in the treatment of cough variant asthma.

BACKGROUND: Antileukotriene agents have been shown to be beneficial in chronic asthma. Although patients with cough variant asthma have cough with minimal wheezing and dyspnea, airway hyperresponsiveness from chronic inflammation is believed to be the underlying mechanism. OBJECTIVE: To evaluate the effectiveness of montelukast, a leukotriene receptor antagonist, in the treatment of cough variant asthma. METHODS: Fourteen patients with cough variant asthma participated in a randomized, double-blind, placebo-controlled trial with a 7- to 10-day baseline period and a 4-week treatment period with montelukast, 10 mg, or placebo daily. Inclusion criteria were (1) chronic cough with a duration of at least 4 weeks with minimal or no wheezing or dyspnea and (2) forced expiratory volume in 1 second of 50% to 85% of predicted and reversibility of 12% with use of an inhaled beta-agonist or forced expiratory volume in 1 second greater than 85% and positive methacholine challenge results. Patients fulfilled the minimum criteria for cough frequency and symptom scores for randomization. RESULTS: Eight patients received montelukast and 6 received placebo. The primary efficacy variable, mean percentage change from baseline in cough frequency, was significantly improved by the second week, and by the fourth week the mean percentage change from baseline was 75.7% for the treatment group and 20.7% for the placebo group. CONCLUSIONS: The leukotriene receptor antagonist montelukast seems to be effective in the treatment of cough variant asthma. Larger studies are recommended to confirm this effect.     

Alpha-smooth muscle actin in pathological human disc nucleus pulposus cells in vivo and in vitro

That a contractile actin isoform has been found in cells of other cartilage tissues in healing and disease states prompted this investigation of the presence of alpha-smooth muscle actin (alpha-SMA) in pathological human intervertebral disc tissue. The presence of this isoform has been reported in human intervertebral disc specimens obtained at autopsy from subjects for whom there were no reported symptoms. An objective of this study was to evaluate the cell density and percentage of alpha-SMA-containing cells in pathological nucleus pulposus tissue obtained from lumbar disc surgery from 17 patients. Additionally, explants of nucleus pulposus material were cultured to determine how alpha-SMA expression changed with time in vitro. Seventy-six 5-mm diameter explants (approximately 2 mm thick) pooled from six lumbar surgeries were cultured for 1, 2, 4, or 6 weeks. Microtomed sections of paraffin-embedded specimens were stained with hematoxylin and eosin or a monoclonal antibody to alpha-SMA. Histologically, cells were categorized as to alpha-SMA phenotype (positive or negative), and the areal cell density was determined. The evaluation of the cultured nucleus pulposus explants also included documentation of the percentage of cells that were round or elongated and the percentage of the cells that were part of a group (group: >/= 2 cells). Every nucleus pulposus section exhibited the presence of alpha-SMA-containing cells, which accounted for approximately 24 percent of the cells in vivo. In vivo, the cell density was significantly higher in older individuals (p = 0.02). The average time for cell outgrowth from the explants was 8.6 days. Approximately 10-15 percent of the cells in the explants stained positive for alpha-SMA. The time in culture had no significant effect on any of the outcome measures except the percentage of alpha-SMA-containing cells that were round (p = 0.008), with values decreasing through 4 weeks and then slightly rising at 6 weeks. The role of alpha-SMA in intervertebral disc pathology warrants further investigation.     

Reversal of dexfenfluramine-induced anorexia and c-Fos/c-Jun expression by lesion in the lateral parabrachial nucleus

The external subdivision of the lateral parabrachial nucleus (LPBE) shows strong Fos-like immunoreactivity (FLI) following anorectic doses of the indirect serotonin agonist dexfenfluramine (DFEN). In an effort to determine the contribution of the LPBE to DFEN-induced anorexia, bilateral ibotenate lesions were made in the LPBE, and the effects of the lesion on DFEN-induced anorexia and FLI as well as c-June-like immunoreactivity (JLI) were examined. It was found that LPBE lesion significantly attenuated DFEN anorexia: in a 1-h food intake test following 24-h food deprivation, DFEN (2 mg/kg) suppressed food intake by 60% in intact rats but only 34% in rats with LPBE lesions. In addition to this behavioral change, LPBE lesion completely abolished DFEN-induced FLI and JLI in the lateral subdivision of the central nucleus of the amygdala (CeL) and laterodorsal subdivision of the bed nucleus of stria terminalis (BSTLD), both of which showed strong FLI and JLI in intact rats. DFEN-induced FLI and JLI in other brain regions were not affected by LPBE lesion, including the ventromedial and lateral hypothalamus, caudate-putamen, and the nucleus of the solitary tract (NST). The parallel loss of DFEN-induced anorexia and FLI/JLI following LPBE lesion raises the novel possibility that LPBE-CeL/BSTLD pathway may be involved in DFEN anorexia.     

Geriatric care on a ward without nurses

The Multiphasic Environmental Assessment Procedure (MEAP; Moos and Lemke, 1984) was used to assess three long-stay settings within a geriatric hospital, one of which is a non-nursing unit committed to the philosophy of residents viewing the setting as their own home. Findings suggest positive outcomes for residents on the nonnursing unit, and support the view that types of care fostering independence and personal responsibility of elderly residents in their setting may be associated with increased mental functioning and activity. The lack of trained nursing staff had no detrimental effect on any measure of resident life, and some specific caring practices on the unit may be interpreted as having a positive outcome for residents.     

Incidence of AIDS dementia in a two-year follow-up of AIDS and ARC patients on an initial phase II AZT placebo-controlled study: San Diego cohort.

In a prospective study to determine the incidence of clinical dementia in patients with AIDS and ARC, 29 men and 3 women, 19 with ARC and 13 with AIDS, were examined neurologically and neuropsychologically every 6 months for 2 years during a placebo-controlled zidovudine (AZT) licensing trial. Most received two MRI brain scans. Although no patient was clinically demented at baseline, 9 (28%) developed dementia during the 2 years. Progression to dementia was associated with neuropsychological deterioration and with worsening on MRI during a preceding 6-month period, but not with baseline treatment group assignment. The results suggest that patients at CDC Stage IV who do not receive antiretroviral treatment earlier in their illness may develop clinical dementia at an annual rate of about 14%.     

Three cases of infection withFusarium species in neutropenic patients

Three cases are reported of disseminated infection due toFusarium species in severely neutropenic patients. The clinical findings in all patients included fever, painful disseminated nodular skin lesions and severe myalgia. The outcome was fatal despite early administration of amphotericin B. The portal of entry of the organism was probably the nasal sinus in two cases.