Brian M. Murray

BACKGROUND: Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection. METHODS: A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant. RESULTS: Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study. CONCLUSION: Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.

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 evidence-based 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: Five general themes emerged as key findings: (1) lack of awareness of K/DOQI guidelines; (2) Desire for more CKD practice guidance; (3) persistence of traditional, less accurate, diagnostic procedure; (4) variability in the treatment of complications; and (5) uncertainty of timing for referral to a nephrologist. CONCLUSION: Facing a growing CKD incidence, PCPs can have an impact on preventing its progression and associated complications with increased familiarity of new guidelines.

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 II. The pressor response to angiotensin II was significantly lower in conscious cirrhotic animals than in controls. On the other hand, cirrhotic animals had normal pressor responses to norepinephrine, indicating that a generalized defect in vascular reactivity does not cause the decreased pressor response to angiotensin II. Enhanced baroreceptor activity was not the cause of the decreased pressor response to angiotensin II, since baroreflex control of heart rate after angiotensin II was similar in cirrhotics 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 II, was significantly lower than in controls (kd: cirrhosis 1.11 +/- 0.09 nM, control 0.94 +/- 0.13 nM; P less than 0.02), whereas receptor number was significantly increased (cirrhosis 315 +/- 42 fmol/mg protein, control 277 +/- 43 fmol/mg protein, P less than 0.01). However, total binding of AII by vascular receptors from cirrhotics was no different than in controls, since the decrease in affinity negated the increase in receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)

BVRI and H-alpha imaging and long-slit optical spectroscopic data are presented for four morphologically normal and relatively isolated Sa galaxies, NGC3626, NGC3900, NGC4772 and NGC5854. VLA HI synthesis imaging is presented for the first 3 objects. In all 4 galaxies, evidence of kinematic decoupling of ionized gas components is found; the degree and circumstances of the distinct kinematics vary from complete counterrotation of all of the gas from all of the stars (NGC3626) to nuclear gas disks decoupled from the stars (NGC5854) to anomalous velocity central gas components (NGC3900 and NGC4772). In the 3 objects mapped in HI, the neutral gas extends far beyond the optical radius, R_HI/R_25 > 2. In general, the HI surface density is very low and the outer HI is patchy and asymmetric or found in a distinct ring, exterior to the optical edge. While the overall HI velocity fields are dominated by circular motions, strong warps are suggested in the outer regions. Optical imaging is also presented for NGC 4138 previously reported by Jore et al. (1996) to show counterrotating stellar components. The multiwavelength evidence is interpreted in terms of the kinematic "memory" of past minor mergers in objects that otherwise exhibit no morphological signs of interaction.