Elevated NMDA receptors in parkinsonian striatum.

Dopamine-glutamate interactions contribute to normal striatal function and have been implicated in neurotoxicity at nigrostriatal dopamine (DA) terminals. The present study examined the striata of idiopathic Parkinson's disease (PD) patients and age-matched controls for regional differences in the DA transporter and binding to N-methyl-D-aspartate (NMDA) receptors. [3H]Mazindol labeling of the DA transporter was reduced by 70-80% in the caudate and putamen of PD patients, with reductions being more extensive dorsally than ventrally. In contrast, L-[3H]glutamate binding to NDMA-sensitive receptors was 20-40% higher in PD cases than in controls. These findings raise the possibility that modifications occur within corticostriatal glutamate synapses of PD patients, possibly as a consequence of reduced nigrostriatal DA activity.     

Nosocomial viral infections in a pediatric service: example of rotaviral gastroenteritis and respiratory syncytial viral bronchiolitis]

Nosocomial infections are a preoccupation in a pediatric hospital mainly during the winter with bronchiolitis and gastroenteritis epidemics. We have examined the risk factors of nosocomial infections. MATERIAL AND METHODS: A prospective study was conducted between November, 1999 and March, 2000 in the infants units of the Le Havre hospital. We systematically listed the admissions and contacted the family after their discharge by phone. A geographic information system was implemented to display the epidemiological data; this software is able to illustrate the sectors at risk. RESULTS: During the study, 687 infants were hospitalized of whom 458 for bronchiolitis and community-acquired gastroenteritis. Mean age was 5.4 months old. No nosocomial bronchiolitis occurred. Prevalence of nosocomial gastroenteritis was 10% (68 cases including nine after discharge). Infants with nosocomial infection were younger than those with community-acquired infection (6.6 months vs. 11.2 months, P < 0.01). The mean length of stay was longer in nosocomial infection (7.7 vs. 4.1 days, P < 0.05). Among the infants with bronchiolitis, 16% have developed nosocomial intestinal infections (RR = 2.65, IC: 1.59-4.4; P < 0.01). The geographic analysis pointed the area with nosocomial risk (bedroom without water, nearness of nurse office and games room). CONCLUSION: Geographic information system is a part of the quality control system and may have some interaction effect on final decision making. Incidence of nosocomial infections showed the need for a prevention strategy in a pediatric hospital.     

Blood pressure and retinopathy in type I diabetes

The relationship between blood pressure and diabetic retinopathy was evaluated in 249 young subjects with type I diabetes. Although hypertension is known to be associated with an increased risk for retinopathy, the effects of high-normal blood pressure are unknown. Retinopathy (158 of 249 subjects, 63%) is considerably more common in a young diabetic population than is hypertension (7 of 249 subjects, 2%). Thus, if blood pressure is important in the etiology or progression of diabetic retinopathy, levels below the hypertensive range (less than 141/90 mmHg) must be considered. The combined effect of hypertension and high-normal blood pressure (greater than 90th percentile but less than 141/90 mmHg) was studied. Elevation in diastolic blood pressure, alone, and in combination with elevated systolic blood pressure, correlated significantly (P less than 0.03) with retinopathy. The presence of high-normal blood pressure resulted in a prospectively higher occurrence of retinopathy and of progression of preexisting retinopathy. Glycohemoglobin (HbA1) and duration of diabetes also correlated with retinopathy. Both good glycemic control and maintenance of diastolic blood pressure below the 90th percentile for age may be important in relation to diabetic retinopathy.     

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Purpose  

An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.     

Population-based randomized controlled trial of a stage-targeted physical activity intervention

Background: Intervention trials with self-selected participants have shown that mailed stage-targeted print materials can increase participation in physical activity in the short term. We examined the effects of a mailed stage-targeted print intervention designed to promote physical activity, in a random sample of adults living in a regional city.Method: Participants (n = 462, 40–60 years of age) were randomly allocated to an intervention in - 227) or control group (n - 235). Measures included validated 2-week physical activity recall and stage of motivational readiness for physical activity. The intervention consisted of a single mailing of a letter and full-color stage-targeted booklets (specific to precontemplation, contemplation, preparation, and action/maintenance) 1 week postbaseline. Follow-up interviews were conducted at 2 and 6 months postbaseline.Results: After 2 months, participants in the intervention group were significantly More likely to meet the current American College of Sports Medicine/Centers for Disease Control and Prevention recommendation for sufficient physical activity than those in the control group (adjusted odds ratio [OR] - 2.40; 95% confidence interval [CI] = 1.44–3.99). After 6 months, intervention participants who reported receiving and reading the intervention materials were significantly more likely to be meeting the sufficient physical activity criterion compared with the control group (adjusted OR = 2.03; 95% Cl = 1.16–3.56).Conclusions: The stage-targeted print intervention was effective in promoting short-term increases in physical activity and was most effective for participants who recognized and used the materials. This low-cost, generalizable intervention has demonstrated potential as a practical population-based physical activity promotion strategy. Further research is required before widespread dissemination would be justified, as additional strategies may be required to ensure sustained change. This project was supported by a National Heart Foundation of Australia Research Project Grant. David Crawford was supported by a Nutrition Research fellowship from the National Heart Foundation.     

Inactivation of human synovial fluid phospholipase A2 by the marine natural product, manoalide

The marine natural product, manoalide (MLD), was investigated to determine if this drug inhibited purified human synovial fluid phospholipase A2 (HSF-PLA2). Utilizing classical Michaelis-Menten kinetics, apparent Km and Vmax values for HSF-PLA2 of 1.34 mM and 0.47 mumol [3H]palmitic acid released/min/mg protein were obtained using dipalmitoylphosphatidylcholine (DPPC) as the substrate, and 38.0 microM and 18.8 mumol [3H]arachidonic acid released/min/mg protein with Escherichia coli as a natural substrate. These kinetic parameters were utilized subsequently to evaluate the inhibitory effects of manoalide on HSF-PLA2. Inhibition of HSF-PLA2 by MLD was concentration and time dependent with IC50 values of 0.2 and 0.02 microM for DPPC and E. coli respectively. Dialysis studies and examination of DPPC or E. coli hydrolysis versus enzyme concentration indicate that MLD is an irreversible inhibitor of HSF-PLA2. Substrate specificity was also examined in the absence and presence of MLD using dipalmitoylphosphatidylethanolamine (DPPE) as a substrate. MLD inhibited the hydrolysis of DPPE (greater than 90% inhibition at 2 microM), and preliminary results indicate that DPPC was more readily hydrolyzed than DPPE under the substrate conditions of the assay. While the cellular source of secreted HSF-PLA2 is unknown, these studies indicate that MLD can inactivate secreted phospholipase A2 isolated from patients with inflammatory joint disease.