The effect of acute and chronic administration of cyclosporine on systemic and renal hemodynamics was studied in conscious rats. Infusion of cyclosporine in a dose of 20 mg/kg (Cy 20) resulted in a significant fall in renal blood flow (RBF) (3.4 vs. 6.5 ml/min/g, P less than 0.05) and a rise in renal vascular resistance (RVR) (36.9 vs. 20.6 mm Hg/ml/min/g, P less than 0.05). Infusion of cyclosporine at a dose of 10 mg/kg (Cy 10) did not result in a significant change in RBF or RVR. Both doses of cyclosporine resulted in stimulation of plasma renin activity (PRA) from control values of 5.6 +/- 0.8 ng/ml/hr to 11.6 +/- 2.0 with 10 mg/kg and 26.7 +/- 5.6 with 20 mg/kg. Urinary 6-keto-PGF1 alpha excretion increased from control values of 14.0 +/- 2.0 ng/6 hr to 22.7 +/- 2.2 with 10 mg/kg and 25.0 +/- 2.0 with 20 mg/kg. Similar effects on RBF, RVR, PRA, and 6-keto-PGF1 alpha excretion were seen after chronic administration of cyclosporine (20 mg/kg i.p. for 7 days). Pretreatment of animals with captopril did not prevent the fall in RBF after cyclosporine, suggesting that the vasoconstriction was not mediated by angiotensin II. Animals treated with meclofenamate demonstrated reduction in RBF with 10 mg/kg cyclosporine (4.3 vs. 7.0 ml/min/g, P less than 0.05), suggesting that prostaglandins protect against the vasoconstrictor effect of cyclosporine. Administration of phenoxybenzamine after cyclosporine improved RBF (5.0 vs. 3.4 ml/min/g) and restored RVR to normal. Similarly, renal denervation dramatically reduced the fall in RBF after cyclosporine (innervated right kidney 3.6 vs. denervated left kidney 6.0 ml/min/g, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

BVRI and Hα imaging and long-slit optical spectroscopic data are presented for four morphologically normal and relatively isolated Sa galaxies, NGC 3626, NGC 3900, NGC 4772 and NGC 5854. VLA H I synthesis imaging is presented for the first three objects. In all four galaxies, evidence of kinematic decoupling of ionized gas components is found in the long-slit spectroscopic data; the degree and circumstances of the

Background: There is a steady increase in the prevalence of chronic kidney disease (CKD) in the United States. Primary care physicians (PCPs) can engage in strategies that are proven to be effective in reducing the progression rate of kidney disease. The National Kidney Foundation has released evidencebased guidelines called the Kidney Disease Outcome Quality Improvement Initiative (K/DOQI) that detail these strategies. No information exists regarding adoption of these guidelines in primary care.Methods: A qualitative study in a practice-based research network (PBRN) was undertaken to explore common PCP practices and knowledge regarding CKD. A typical case sampling strategy was followed. Semi-structured interviews and exit surveys were conducted with 10 PCPs from randomly selected PBRN practices. Three reviewers conducted content analysis using the immersion-crystallization approach.Results

We extend previous work showing that violation of the null energy condition implies instability in a broad class of models, including gauge theories with scalar and fermionic matter as well as any perfect fluid. Simple examples are given to illustrate these results. The role of causality in our results is discussed. Finally, we extend the fluid results to more general systems in thermal equilibrium. When applied to the dark energy, our results imply that w is unlikely to be less than -1.Comment: 11 pages, 5 figures, Revte

Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.

Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

Background: With the prevalence of chronic kidney disease (CKD) in the United States rising from 10% to 13%, implementation of the evidence-based Kidney Disease Outcomes Quality Initiative guidelines, which were developed for the delay of progression of CKD, is of increasing importance in primary care offices. Previous studies have shown limited knowledge and uptake of Kidney Disease Outcomes Quality Initiative guidelines by primary care physicians. CKD and its complications are still largely under-diagnosed and under-treated. A multifaceted quality improvement study was undertaken to test if these guidelines could be implemented to improve CKD care in underserved practices.Methods: Using a combination of practice enhancement assistants, computer decision-making support, and academic detailing, we sought to increase physician awareness and care of CKD in 2 inner-city practices. Using these 3 modalities, a rapid-cycle quality improvement process was implemented.Results: One hundred eighty-one patients met the inclusion criteria of having a glomerular filtration rate <60. This represented a 100% sample of patients with CKD at baseline. Recognition of CKD improved significantly from 30 (21%) to 114 (79%) (P < .001). Diagnosis of anemia also increased significantly from 26 (33%) to 53 (67%) (P < .001). Angiotensin-converting enzyme inhibitor and aspirin use did not change significantly (P ‫؍‬ .31 and P ‫؍‬ .233, respectively). Changes in medications that did show significance were metformin use, which decreased 50% from 12 to 6 patients (P < .001), and nonsteroidal anti-inflammatory drug use, which decreased 41% from 23 to 14 patients (P < .001). Mean glomerular riltration rate increased significantly from 45.75 to 47.34 (P < .001).Discussion: Recognition and treatment of CKD and its complications can be markedly improved in primary care offices using a combination of practice enhancement assistants, computer decision-making support, and academic detailing. A significant rise in glomerular riltration rate, although small, was a surprising and encouraging result. Larger studies in a more geographically spread region are needed to confirm these preliminary results.

SUMMARY. We used a model of cirrhosis in the rat, produced by inhalation of carbon tetrachloride for 6 weeks, to investigate the mechanism of resistance to the pressor effects of angiotensin H The pressor response to angiotensin II was significantly lower in conscious cirrhotic animals than in controls. On the other hand, drrhotic animals had normal pressor responses to norepinephrine, indicating that a generalized defect in vascular reactivity does not cause the decreased pressor response to angiotensin D. Enhanced baroreceptor activity was not the cause of the decreased pressor response to angiotensin II, since baroreflex control of heart rate after angiotensin D was similar in drrhotics and controls. Pretreatment with either the converting enzyme inhibitor captopril to reduce circulating angiotensin II or the prostaglandin synthesis inhibitor meclofenamate failed to normalize the response to angiotensin II. Thus, neither prior occupancy of receptors with endogenous angiotensin II nor the production of vasodilatory prostaglandins was responsible for the decreased angiotensin II response. Studies of angiotensin II binding by mesenteric artery smooth muscle particles showed that, in cirrhotic animals, receptor affinity for angiotensin n, was significantly lower than in controls (kj: cirrhosis 1.11 ± 0.09 nM, control 0.94 ± 0.13 nM; P < 0.02), whereas receptor number was significantly increased (cirrhosis 315 ± 42 fmol/mg protein, control 277 ± 43 fmol/mg protein, P < 0.01). However, total binding of All by vascular receptors from drrhotics was no different than in controls, since the decrease in affinity negated the increase in receptor number. Similar receptor abnormalities have been found in potassium deficiency, although plasma and muscle potassium were normal in cirrhotic animals. We conclude that the decreased pressor response to angiotensin II in cirrhosis is the result of a post-receptor defect in angiotensin action. (Circ Res 57: 424-431, 1985) STUDIES in experimental models of cirrhosis in both the dog (Shasha et al., 1976;Levy, 1977) and rat (linas et al., 1981) have shown that cirrhosis is characterized by both an increase in cardiac output and a decrease in systemic vascular resistance. The mechanism of systemic vasodilation in cirrhosis remains unclear, but its presence in the face of activation of the rerun angiotensin system suggests that there is decreased responsiveness of vascular smooth muscle to the pressor action of endogenous angiotensin II (All). Resistance to the pressor effect of exogenous All has also been observed in patients with cirrhosis (Laragh et al., 1963), and a similar defect has been seen in the bile duct-ligated dog (Finberg et al., 1981). Several mechanisms have been proposed to explain a decreased pressor response to AH including: (1) a generalized decrease in vascular reactivity, (2) alteration of baroreceptor activity, (3) prior occupancy of receptors by endogenous All, (4) enhanced production of vasodilator substances, such as prostaglandins, and (5) alteration in th...