In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.     

Adenosine receptor-induced cyclic AMP generation and inhibition of 5-hydroxytryptamine release in human platelets.

1. We have assessed the effects of adenosine receptor agonists and antagonists on collagen-induced 5-hydroxytryptamine (5-HT) release and cyclic AMP generation in human platelets. 2. 5'-N-ethylcarboxamidoadenosine (NECA) and CGS 21680 elicited accumulations of cyclic AMP with mean EC50 values of 2678 and 980 nM, respectively. The maximal response to CGS 21680 was approximately half that of the response to 10 microM NECA. 3. NECA and CGS 21680 inhibited collagen-induced 5-hydroxytryptamine release with mean EC50 values of 960 and 210 nM, respectively. The maximal response to CGS 21680 was approximately 25% of the response to 10 microM NECA. 4. The A1/A2a-selective adenosine receptor antagonist PD 115,199 was more potent as an inhibitor of NECA-elicited responses than the A1-selective antagonist DPCPX with calculated Ki values of 22-32 nM and > 10 microM, respectively. 5. In the presence of a cyclic AMP phosphodiesterase inhibitor, the effects of CGS 21680 on cyclic AMP accumulation and 5-HT release were enhanced to levels similar to those elicited by 10 microM NECA. In the absence of phosphodiesterase inhibition, CGS 21680 did not antagonise the effects of NECA. Furthermore, endogenous adenosine did not contribute to the effects of CGS 21680 when phosphodiesterase was inhibited. 6. We conclude that an A2a adenosine receptor appears to be involved in the NECA-elicited increases in cyclic AMP levels and inhibition of 5-HT release in human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Outcome Following Bariatric Surgery in Super versus Morbidly Obese Patients: Does Weight Matter?

Background: Numerous investigators have attempted to identify prognostic indicators for successful outcome following bariatric surgery. The purpose of this study was to determine whether degree of obesity affects outcome in super obese [>225% ideal body weight (IBW)] versus morbidly obese patients (160-225% IBW) undergoing gastric restrictive/bypass procedures. Methods: Since 1984, 157 patients underwent either gastric bypass or vertical banded gastroplasty. Super obese (78) and morbidly obese (79) patients were followed prospectively, documenting outcome and complications. Results: Super obese patients reached maximum weight loss 3 years following bariatric surgery, exhibiting a decrease in body mass index (BMI) from 61 to 39 kg/m² and an average loss of 42% excess body weight (EBW). Morbidly obese patients had a decrease in BMI from 44 to 31 kg/m² and carried 39% EBW at 1 year. After their respective nadirs, each group began to regain the lost weight with the super obese exhibiting a current BMI of 45 kg/m² (61% EBW) versus 34 kg/m² (52% EBW) in the morbidly obese at 72 months cumulative follow-up. Currently, loss of 50% or more of EBW occurred in 53% of super obese patients versus 72% of morbidly obese (P < 0.01). Twenty-six percent of super obese patients returned to within 50% of ideal body weight (IBW) while 71% of morbidly obese were able to reach this goal (P < 0.01). Co-morbidities and complications related to surgery were similar in each group. Conclusions: Super obese patients have a greater absolute weight loss after bariatric surgery than do morbidly obese patients. Using commonly utilized measures of success based on weight, morbidly obese patients tend to have better outcomes following bariatric surgery.     

Prodromal frontal/executive dysfunction predicts incident dementia in Parkinson's disease.

To identify the cognitive characteristics predictive of incident dementia in Parkinson's disease (PD), we examined the baseline neuropsychological profiles of 18 initially non-demented patients with PD who met diagnostic criteria for dementia (PDD) at one-year follow-up. PDD participants' baseline neuropsychological test scores were compared to the baseline performance of 18 patients with PD who did not meet criteria for dementia at one-year follow-up (PDND) and 18 normal controls (NC). The three groups were matched on baseline demographic and disease variables. Relative to the PDND group, the incident PDD participants demonstrated significantly poorer performance on digits backward (Wechsler Memory Scale-Revised), word list learning and recognition (California Verbal Learning Test), and perseverative errors on the Wisconsin Card Sorting Test. Each of these baseline neuropsychological variables exhibited adequate diagnostic classification accuracy in predicting PDD and PDND group membership at follow-up. These results suggest that subtle frontal/executive dysfunction is evident during the immediate PDD prodrome and may be of prognostic value in identifying PD patients at risk for dementia. Accordingly, neuropsychological evaluation may facilitate early identification of PDD and thereby inform appropriate dispositional planning.     

XIVth World Congress of Pharmacology San Francisco,CA, July 7–12, 2002 New Cardiovascular Drugs

The XIVth World Congress of Pharmacology took place July 7–12, 2002 in Moscone Convention Center, San Francisco, CA. Over 4,000 scientists, exhibitors and guests attended the Congress. It consisted of 40 symposia, 11 workshops, 18 plenary lectures and ca. 1,400 posters. The Congress was sponsored by the American Society for Pharmacology and Experimental Therapeutics, Inspire Pharmaceuticals and GlaxoSmithKline. The major financial donors were: Eli Lilly and Company, Servier, Johnson & Johnson, Merck, Novartis, Roche, Schering‐Plough, Wyeth and Yamanouchi Foundation. This report covers only presentations and posters on drugs that were attended or viewed by the author.     

Myocardial metabolic imaging by means of fluorine-18 deoxyglucose/technetium-99m sestamibi dual-isotope single-photon emission tomography

The detection of preserved glucose uptake in hypoperfused dysfunctional myocardium by fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) represents the method of choice in myocardial viability diagnostics. As the technique is not available for the majority of patients due to cost and the limited capacity of the PET centres, it was the aim of the present work to develop and test FDG single-photon emission tomography (SPET) with the means of conventional nuclear medicine. The perfusion marker sestamibi (MIBI) was used together with the metabolic tracer FDG in dual-isotope acquisition. A conventional SPET camera was equipped with a 511-keV collimator and designed to operate with simultaneous four-channel acquisition. In this way, the scatter of 18F into the technetium-99m energy window could be taken into account by a novel method of scatter correction. Thirty patients with regional wall motion abnormalities at rest were investigated. The results of visual wall motion analysis by contrast cine-ventriculography in nine segments/heart were compared with the results of quantitative scintigraphy. The scintigraphic patterns of MIBI and FDG tracer accumulation were defined as normal, matched defects and perfusion-metabolism mismatches. Spatial resolution of the system was satisfactory, with a full width at half maximum (FWHM) of 15.2 mm for ¹⁸F and 14.0 mm for ^99mTe, as measured by planar imaging in air at 5 cm distance from the collimator. Image quality allowed interpretation in all 30 patients. 88% of segments without relevant wall motion abnormalities presented normal scintigraphic results. Seventy-five akinetic segments showed mismatches in 27%, matched defects in 44% and normal perfusion in 29%. We conclude that FDG-MIBI dual-isotope SPET is technically feasible with the means of conventional nuclear medicine. Thus, the method is potentially available for widespread application in patient care and may represent an alternative to the ²⁰¹T1 reinjection technique.     

Application of attachment theory to the study of sexual abuse.

Research on sexual abuse frequently fails to address the influence of the family as a risk factor for the onset of all kinds of sexual abuse and as a mediator of its long-term effects. Attachment theory provides a useful conceptual framework for understanding the familial antecedents and long-term consequences of sexual abuse. Themes associated with insecure parent-child attachment (rejection, role reversal/parentification, and fear/unresolved trauma) are frequently found in the dynamics of families characterized by sexual abuse, and specific categories of sequelae are related to probable attachment experiences. Implications for intervention and research on sexual abuse are suggested.