Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has demonstrated significant antiparkinsonian actions in several animal models and in a recent pilot study in England in which four of five patients received bilateral putaminal delivery. In the present study the authors report on a 6-month unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson disease (PD). METHODS: Patients with PD in a functionally defined on and off state were evaluated 1 week before and 1 and 4 weeks after intraputaminal catheter implantation in the side contralateral to the most affected side. Each patient was placed on a dose-escalation regimen of GDNF: 3, 10, and 30 microg/day at successive 8-week intervals, followed by a 1-month wash-out period. The Unified Parkinson's Disease Rating Scale (UPDRS) total scores in the on and off states significantly improved 34 and 33%, respectively, at 24 weeks compared with baseline scores (95% confidence interval [CI] 18-47% for off scores and 16-51% for on scores). In addition, UPDRS motor scores in both the on and off states significantly improved by 30% at 24 weeks compared with baseline scores (95% CI 15-48% for off scores and 5-61% for on scores). Improvements occurred bilaterally, as measured by balance and gait and increased speed of hand movements. All significant improvements of motor function continued through the wash-out period. The only observed side effects were transient Lhermitte symptoms in two patients. CONCLUSIONS: Analysis of the data in this open-label study demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF infusion. Unilateral administration of the protein resulted in significant, sustained bilateral effects.     

A model for closure of arterial vessels with special regard to the coronary arteries

Summary To explain the closure of an arterial vessel we derived a model of the vascular bed. We checked this model by calculating the pressure losses. Excellent agreement was found with experimental evidence. From fluid mechanical considerations it can be shown that a stenosis in an arterial main branch does not change the blood flow in that branch appreciably. However, in the presence of aggregates of blood particles, a stenosis will produce an inhomogeneous distribution of aggregates. The concentration of aggregates in the core régime of the stenosis and in the dead-water region downstream of the stenosis could reach values high enough to make blood clotting likely. From these results the prevention of the formation of large aggregates of particles in the clinical setting seems to be very important.

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Ein Modell zur Darstellung des arteriellen Gefäßverschlusses unter besonderer Berücksichtigung der Koronararterien

Zusammenfassung Zur Erklärung eines Arterienverschlusses wird zunächst ein Gefäßmodell entwickelt. Dieses Modell wird überprüft, indem der Druckabfall berechnet und mit Messungen verglichen wird. Die Berechnung des strömungsmechanischen Einflusses einer Stenose in einem Arterienhauptzweig ergibt, daß erst sehr beträchtliche Verengungen den Durchfluß merklich mindern. Falls jedoch durch Zusammenballung oder Aggregatbildung größere Teilchen im Blut auftreten, verursachen Entmischungseffekte in der Stenose eine inhomogene Verteilung der größeren Teilchen. Die Teilchenkonzentration im Kern der Stenosenströmung und im Totwassergebiet stromab von der Stenose kann dabei so groß werden, daß ein Verschluß vorstellbar ist Es scheint daher besonders wichtig zu sein, die Bildung großer Teilchenaggregate zu verhindern.

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With 8 figures and 1 table     

Decreasing overuse of therapies in the treatment of bronchiolitis by incorporating evidence at the point of care

OBJECTIVE: To describe the effect of evidence-based point-of-care algorithms and rules, based on guideline recommendations, on the overuse of therapies for bronchiolitis.Study design Pre-postintervention for infants <1 year of age admitted with a first-time episode of bronchiolitis. Data collected for guideline-eligible patients discharged between January 15, 2002, and March 27, 2002, were compared with data collected for guideline-eligible patients discharged from the hospital with a diagnosis of bronchiolitis during the same time period in the first 5 years after the original guideline implementation (1997 to 2001). The primary outcome of interest was use of bronchodilator therapy. Secondary outcomes included use of guideline order sets, resource utilization, length of stay, and readmission. RESULTS: A total of 256 patients from 2002 were compared with 1272 historic patients. In 2002, the odds of receiving any bronchodilator, more than 1, more than 2, and more than 4 bronchodilators were all significantly less than predicted by the 1997 to 2001 year-to-year trend. The odds of receiving a nasopharyngeal wash for respiratory syncytial virus and a chest radiography (OR=0.680, CL=0.476, 0.973) were also significantly lower than what was predicted from use trends of previous years. CONCLUSIONS: Evidence-based point-of-care instruments can have a significant effect on unwarranted treatment variation.     

Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model

BACKGROUND: ISATX247 is a novel calcineurin inhibitor that has shown more potency than cyclosporine in vitro. This is the first study to compare the survival times of renal allografts in nonhuman primates treated with either ISATX247 or cyclosporine. METHODS: Adult, male cynomolgus monkeys were divided into blood-group compatible and mixed-lymphocyte, stimulation-mismatched, donor-recipient pairs. Heterotopic renal transplantation and bilateral native nephrectomies were performed. The monkeys were placed into either an ISATX247 or cyclosporine treatment group. Both groups were dosed twice daily to maintain a 12-hour drug-trough level of 150 ng/mL. Whole-blood concentrations of ISATX247 and cyclosporine, complete blood counts, and serum chemistry profiles were performed three times a week. Euthanasia was performed if the serum creatinine concentration became 7 or more mg/dL or a serious complication developed. RESULTS: The group receiving ISATX247 (n=8) survived significantly (P=0.0036) longer than the group receiving cyclosporine (n=7). The mean trough blood concentration of ISATX247 was 120 +/- 32 ng/mL and cyclosporine was 189 +/- 130 ng/mL. The average area under the curve 0-12 for ISATX247 was 6045 +/- 1679 ng/mL/hr and for cyclosporine was 4919 +/- 823 ng/mL/hr. The average calcineurin inhibition at trough blood concentrations was 80 +/- 11% for ISATX247 and 48 +/- 12% for cyclosporine. CONCLUSIONS: Allografts in monkeys treated with ISATX247 survived significantly longer than those treated with cyclosporine. On the basis of survival times and degree of calcineurin inhibition, ISATX247 is a more potent immunosuppressive agent than cyclosporine in this nonhuman primate model of renal-allograft transplantation.     

Regional anesthesia techniques for the lower extremity

This article focuses on regional anesthesia for orthopedic procedures of the lower extremity.     

Stability and predictors of health-related quality of life of inner-city girls

Predictors of health-related quality of life (HR-QOL) among inner-city girls and its effect on health care use were evaluated. Adolescent girls aged 14 to 18 years (n = 127) completed a demographic and risk-behavior interview, the Kaufman Brief Intellectual Test, and the Medical Outcomes Study Short Form-36. Medical charts were reviewed for health care use. Two assessments were completed 6 months apart. Participants reported stable and poor HR-QOL compared with norms for similar aged females. HR-QOL was associated with some concurrent risk taking. Lower self-perceptions of mental health were associated with inconsistent condom use, smoking, and alcohol use; lower self-perceptions of physical health were associated with pregnancy and smoking. Predictive associations were not found. There was a trend for poorer physical health to be associated with more clinic visits. This study highlights the need for research aimed at both improving self-perceptions of health and decreasing high-risk behavior among inner-city girls.     

A controlled longitudinal study of the social functioning of children with juvenile rheumatoid arthritis

OBJECTIVE: To complete an assessment of social functioning of children with juvenile rheumatoid arthritis (JRA) and nonchronically ill controls who had been evaluated 2 years earlier (Noll et al., 2000) and to examine the impact of disease severity or disease activity over time on the social functioning of children with JRA. METHODS: Peer-, teacher-, and self-reports of social functioning were obtained from 57 children with JRA and 63 controls. Social reputation and social acceptance were examined cross-sectionally and longitudinally. RESULTS: Cross-sectional analyses indicated no significant differences between children with JRA and controls on measures of social functioning. For children with more severe disease, like ratings declined over the 2-year period relative to children with mild disease. Children with active disease were chosen fewer times over the 2-year period as a best friend than children in remission. CONCLUSIONS: Because children with severe or active JRA may be at risk for difficulties with social acceptance over time, they are appropriate targets for interventions that ameliorate or prevent these difficulties.