Cyclic GMP-independent relaxation and hyperpolarization with acetylcholine in guinea-pig coronary artery.

1. The effects of acetylcholine (ACh) on membrane potential, relaxation and cyclic GMP levels were compared to the NO donor L-nitrosocysteine (Cys-NO) in segments of guinea-pig coronary artery. 2. ACh and Cys-NO produced concentration-dependent relaxations of muscles contracted with the H1 receptor agonist, 2-(2-aminoethyl)pyridine (AEP, 0.35 mM). The relaxation to ACh was unchanged in the presence of NG-monomethyl-L-arginine (L-NMMA; 350 microM) or indomethacin (3 microM). 3. Oxyhaemoglobin (HbO; 20 microM) alone or in combination with L-NMMA increased the EC50 for ACh-induced relaxation whereas relaxation with Cys-NO was almost completely abolished with HbO. 4. Scorpion venom (SV; 8.7 micrograms ml-1) increased the EC50 for relaxation with ACh but not Cys-NO. Combined L-NMMA, HbO and SV produced nearly complete abolition of ACh-induced relaxations. 5. Basal cyclic GMP levels (i.e., 20 pmol mg-1 protein) were significantly increased following addition of either ACh (190 pmol mg-1 protein) or Cys-NO (240 pmol mg-1 protein). L-NMMA significantly reduced the rise of cyclic GMP with ACh but not Cys-NO. In contrast, SV did not significantly reduce the rise in cyclic GMP produced with ACh. In the combined presence of L-NMMA and HbO neither ACh nor Cys-NO produced a significant increase in cyclic GMP levels. 6. ACh gave rise to significantly greater membrane hyperpolarization than Cys-NO both in the presence and absence of AEP. Combined L-NMMA and HbO did not reduce the amplitude of hyperpolarization with ACh.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cancer home care in Montana

Availability of health care services in sparsely populated areas may be limited by fewer health care organizations and geographic separation. The purposes of this study were to identify unmet needs of individuals and families managing cancer in rural areas and examine cancer-related home care in rural areas. Issues of staffing, caseloads and service area for home health agencies (HHAs) and hospices were examined. HHAs registered with the Montana Association of Home Health Care Agencies and licensed hospices in Montana were mailed questionnaires with 92% of the HHAs and 90% of the hospices returning the questionnaires. Health providers identified a variety of unmet needs including personal care and respite. Agencies were small with approximately four full-time equivalent registered nurses for HHAs and one full-time equivalent registered nurse for hospices. Similarly, caseloads were also small with an average of 50 clients per month for HHAs and 11 clients per month for hospices. HHAs and hospices had large service areas with two of the HHAs each serving seven counties. Implications of these findings for research and practice are discussed.     

Right heart catheterization in acute lung injury: an observational study.

Right heart catheterization (RHC) is commonly used in the diagnosis and management of acute lung injury (ALI). However, controversy exists regarding RHC. We examined RHC use during the first 3 d of ALI in an observational study of 135 patients defined by American-European Consensus Conference criteria. Study parameters examined for association with RHC included the Acute Physiology and Chronic Health Evaluation (APACHE) III score, lung injury score (LIS), and 20 additional epidemiologic, clinical, and laboratory parameters. RHC was performed in 70 patients (52%) within the first 3 d of ALI. RHC was positively associated (p < 0.05) with a diagnosis of sepsis, APACHE III score, blood urea nitrogen (BUN), creatinine, net fluid balance, and positive end-expiratory pressure. RHC was negatively associated (p < 0.05) with mean arterial pressure (Pa) and PaO2/FIO2. Logistic regression identified four predictors for RHC placement: sepsis, PaO2/FIO2, BUN, and Pa. Initial right atrial and pulmonary artery occlusion pressure measurements demonstrated a moderately strong correlation (r = 0.72). Use of RHC was associated with a change in one or more therapeutic interventions (intravascular fluids, vasopressors, diuretics) in 78% of patients. In summary, patients receiving RHC during the first 3 d of ALI were more severely ill than those who did not receive RHC, and RHC was associated with a change in therapy in most patients.     

Rapid online quantification of left ventricular volume from real-time three-dimensional echocardiographic data.

AIMS: Determination of left ventricular (LV) volumes and ejection fraction (EF) from two-dimensional echocardiographic (2DE) images is subjective, time-consuming, and relatively inaccurate because of foreshortened views and the use of geometric assumptions. Our aims were (1) to validate a new method for rapid, online measurement of LV volumes from real-time three-dimensional echocardiographic (RT3DE) data using cardiac magnetic resonance (CMR) as the reference and (2) to compare its accuracy and reproducibility with standard 2DE measurements. METHODS AND RESULTS: CMR, 2DE, and RT3DE datasets were obtained in 50 patients. End-systolic and end-diastolic volumes (ESV and EDV) were calculated from the 2DE images using biplane method of disks. ES and ED RT3DE datasets were analysed using prototype software designed to automatically detect the endocardial surface using a deformable shell model and calculate ESV and EDV from voxel counts. 2DE and RT3DE-derived volumes were compared with CMR (linear regression, Bland-Altman analysis). In most patients, analysis of RT3DE data required <2 min per patient. RT3DE measurements correlated highly with CMR (r: 0.96, 0.97, and 0.93 for EDV, ESV, and EF, respectively) with small biases (-14 mL, -6.5 mL, -1%) and narrow limits of agreement (SD: 17 mL, 16 mL, 6.4%). 2DE measurements correlated less well with CMR (r: 0.89, 0.92, 0.86) with greater biases (-23 mL, -15 mL, 1%) and wider limits of agreement (SD: 29 mL, 24 mL, 9.5%). RT3DE resulted in lower intra-observer (EDV: 7.9 vs. 23%; ESV: 7.6 vs. 26%) and inter-observer variability (EDV: 11 vs. 26%; ESV: 13 vs. 31%). CONCLUSION: Semi-automated detection of the LV endocardial surface from RT3DE data is suitable for clinical use because it allows rapid, accurate, and reproducible measurements of LV volumes, superior to conventional 2DE methods.     

MK-801 Administration During Ethanol Withdrawal in Neonatal Rat Pups Attenuates Ethanol-Induced Behavioral Deficits

Alcohol exposure during development can produce central nervous system dysfunction, resulting in a wide range of behavioral alterations. The various mechanisms by which alcohol causes these behavioral changes, however, remain unknown. One mechanism that has been suggested is NMDA receptor-mediated excitotoxic cell death produced by ethanol withdrawal. The present study examined whether MK-801, an antagonist of the NMDA receptor that has been shown to protect against NMDA receptor-mediated excitotoxicity, could block alcohol's adverse effects on behavior. Sprague-Dawley rat pups were exposed to alcohol (6.0 g/kg) in a binge-like manner on postnatal day 6 using an artificial rearing procedure. Subjects then received an injection of MK-801 (0.1 mg/kg) or vehicle during withdrawal, 21 hr after ethanol exposure. At postnatal day 40, all subjects were tested on a serial spatial discrimination reversal task. Ethanolexposed subjects were impaired in both discrimination and reversal learning, and committed a significantly greater number of perseverative-type errors, compared with controls. MK-801 administration during ethanol withdrawal significantly attenuated ethanol-induced deficits in reversal learning and increases in perseverative-type errors, whereas MK-801 exposure by itself had no significant effect on performance. Thus, exposure to MK-801 during ethanol withdrawal partially protected against alcohol-related disruptions in spatial reversal learning. These results support the suggestion that NMDA receptor-mediated excitotoxicity may be one mechanism by which alcohol induces behavioral teratogenicity.     

Low-dose aspirin in patients with diabete melitus: risks and benefits regarding macro and microvascular complications

Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.