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.     

Diagnostic accuracy and variability of autorefraction by the Tracey Visual Function Analyzer and the Shin-Nippon NVision-K 5001 in relation to subjective refraction

Purpose:  To determine the accuracy of distance autorefractions obtained by two 'open field' devices, the Tracey Visual Function Analyzer and the Shin-Nippon NVision-K 5001, by comparison with subjective refraction.
Methods:  Both eyes of 50 healthy phakic participants underwent subjective refraction. Autorefractions were then performed on undilated pupils using the Tracey and a modified Shin-Nippon autorefractor and these were repeated within 50 days. Agreement with subjective refraction was calculated for sphere, mean spherical equivalent (MSE) and cylindrical vectors J ₀ and J ₄₅. Intratest and intertest variability were also evaluated.
Results:  The mean age of the participants was 37.4 years. Subjective refraction MSE ranged from −6.25 D to +3.62 D, mean −0.49 D ± 1.79 D. Bias between subjective refraction and Tracey was −0.001 D, +0.045 D, +0.017 D, and −0.015 D for sphere, MSE, J ₀ and J ₄₅ respectively; these were not significant. Bias between subjective refraction and Shin-Nippon was +0.004 D, +0.033 D, +0.106 D, and −0.021 D; only the J ₀ vector was significantly different ( p  < 0.0001) although this difference was small. Intratest variability for Tracey was low, measured at 0.189 D for sphere and 0.178 for MSE, and for the Shin-Nippon 0.099 D and 0.086 D respectively. Tracey intertest variability revealed small, statistically significant bias for sphere and MSE (+0.071 D and +0.070 D, p  = 0.011, 0.013). Shin-Nippon reproducibility showed no significant bias.
Conclusions:  Autorefraction measurements captured by both the Tracey and Shin-Nippon devices agree well with subjective refraction. The Shin-Nippon shows lower intratest variability.     

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.     

Species-dependent differences in the properties of particulate cyclic nucleotide phosphodiesterase from rat and rabbit ventricular myocardium

The ability of cyclic nucleotide phosphodiesterases (PDEs) to hydrolyse cyclic (c)AMP in rat and rabbit ventricular myocardium has been compared. The PDE activity of rabbit, but not rat, cardiac homogenate and supernatant fraction was potentiated by Ca2+/calmodulin and attenuated by cGMP. Both rabbit and rat ventricular myocardium were shown to have a membrane bound PDE. However, rabbit membrane-bound PDE was inhibited by cGMP and low concentrations of milrinone (IC50 2.7 microM). In contrast, rat membrane-bound PDE was not inhibited by either cGMP or low concentrations of milrinone (IC50 19 microM), but it was potently inhibited by rolipram (IC50 2.2 microM). Thus, in rabbit the particulate PDE is milrinone sensitive (PDE III) whilst in rat it is the rolipram sensitive (PDE IV) isoenzyme. There are clearly species differences in the intracellular localization and relative activities of PDE isoenzymes in cardiac tissue. This may explain the species differences already found in the activity of selective PDE isoenzyme inhibitors as inotropic agents.     

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.