Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation

Cytomegalovirus (CMV) infection is associated with an increased incidence of other opportunistic infections in organ transplant recipients. Whether this is related to immunomodulating effects of CMV or independent of CMV but associated with a host risk factor common to both infections is unclear. The purpose of this study was to determine whether the reduction in CMV infections seen with prophylactic ganciclovir treatment after heart transplantation is associated with a reduced incidence of other opportunistic infections. Of 149 patients prospectively enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of ganciclovir to prevent CMV disease, 74 patients enrolled at this center (33 control and 41 ganciclovir-treated) were retrospectively identified. All received prophylactic OKT-3 and standard 3 drug maintenance immunosuppressive therapy. Actuarial survival and rejection rates and incidence of opportunistic infections (bacterial, fungal, and protozoal) for the 2 treatment groups were determined and compared using Cox-Mantel analysis. CMV disease occurred 2.5 times more frequently in the control group. There were no significant differences in survival or rejection rates nor in bacterial or protozoal infection incidence between the 2 groups. Bacterial infections occurred in 54% of control and 39% of ganciclovir-treated patients (P = 0.18). There were significantly fewer fungal infections in the ganciclovir-treated group (7% vs. 27%, P = 0.0071). CMV and fungal infections were both significantly reduced in patients who received ganciclovir prophylaxis. This suggests that active CMV disease may be causally associated with the development of opportunistic fungal infections.     

Autoradiographic assessment of blood flow heterogeneity in the hamster heart

OBJECTIVE: Provide regional flow measurement in the hearts of small mammals using a new, higher-resolution technique based on the deposition of a molecular marker. METHODS: We determined the instantaneous extraction and retention of the "molecular microsphere" radiolabeled desmethylimipramine in retrogradely perfused hamster hearts. In a separate series of experiments, autoradiography was used to measure regional myocardial deposition densities in hamster hearts of about 0.5 g with spatial area resolution of 16 x 16 microns. RESULTS: Radiolabeled desmethylimipramine is almost 100% extracted during a single transcapillary passage and is retained in the tissue for many minutes. Autoradiographic images demonstrated a spatial flow heterogeneity with standard deviations of 31 +/- 4% of the mean flow (N = 5) in 16 x 16 x 20-micronm3 voxels. This is equivalent to the projections made using fractal relationships from cruder observations obtained with microspheres in the hearts of baboons, sheep, and rabbits. CONCLUSIONS: Autoradiography using a molecular deposition marker provides quantitative information on myocardial flow heterogeneities with resolution at the size of cardiac myocytes. Because the regions resolved are smaller than the volume of regions supplied by single arterioles, the results must slightly exaggerate the true heterogeneity of regional flows.     

Role of metabolism in ethyl carbamate-induced suppression of antibody response to sheep erythrocytes in female Balb/C mice

A possible role of metabolism by cytochrome P450 (P450) in ethyl carbamate-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes (SRBCs), was investigated in female Balb/C mice. When mice were treated with ethyl carbamate intraperitoneally for 14 consecutive days at 25, 50, 100, 200 and 400 mg/kg, the antibody response was significantly suppressed from 200 mg/kg. These doses also caused a decrease in thymus weight. An acute dosing of ethyl carbamate at 1 g/kg also caused not only a significant suppression of the antibody response, but also a decrease in thymus weight. The antibody response was most likely to be the IgM antibody response, which was demonstrated in a haemagglutination study. When mice were pretreated with phenobarbital (80 mg/kg) for 3 days to induce P450 enzymes, followed by administration of ethyl carbamate intraperitoneally for 7 consecutive days, the antibody response was more suppressed than in saline-pretreated controls. Moreover, a study using aminoacetonitrile, a P450 inhibitor, showed that the antibody response suppressed by ethyl carbamate was completely recovered by the inhibitor. The present results suggest that metabolism of ethyl carbamate by P450 may be the critical pathway to produce metabolites capable of suppressing the antibody response.     

Synthesis, binding affinity, and cross-linking of monodentate photoactive phenothiazines to calmodulin

Various photoactive phenothiazines were synthesized that possessed a 2-azido, 3-azido, 2-benzoyl, or 1,3,4-trifluoro-2-azido functionality in combination with various modifications of the N-alkyl side chain. These phenothiazines were evaluated for their ability to inhibit the calmodulin-mediated activation of phosphodiesterase (PDE). All were active in inhibiting the action of calmodulin (CaM), but those possessing either a 3-azido and a 4-(4-methyl-1-piperazinyl)butyl side chain or a 2-benzoyl group and 3-(dimethylamino)propyl side chain proved to be most active (I50 = 14 +/- 3 microM and 7 +/- 1 microM, respectively) when compared to the known inhibitor, chlorpromazine (CPZ, I50 = 30 microM). Calmodulin was photolabeled with ca. 35% efficiency in a light- and calcium-dependent fashion using a radiolabeled analog, 3-azido-10-(4-(4-[14C]methyl-1-piperazinyl)butyl)phenothiazine, of one of these compounds. Competition studies using this radiolabeled analog and CPZ were consistent with binding to one or both of the hydrophobic binding pockets of CaM.     

MR angiography of the peripheral vasculature

MR angiography (MRA) for the evaluation of peripheral arterial occlusive disease is a rapidly evolving technique. Recent prospective clinical trials have indicated that MRA may play an important role in the evaluation of patients with peripheral arterial disease. This article discusses the pertinent technical aspects and limitations of peripheral MRA as well as some of the clinical data available.     

A neglected lesbian health concern: cervical neoplasia

OBJECTIVE: The role of a deficiency of vitamin B1 in the development of alcoholic complaints is confined to the case of the Wernicke-Korsakov syndrome. Findings concerning a deficiency of thiamine in alcoholics in comparison with normal persons are contradictory and there are no differentiated tests in the case of delirium tremens. In this study the vitamin B1 absorption in patients with delirium tremens was of interest in connection with the presence or absence of hallucinations and autonomic symptoms. METHOD: Male patients (N = 70) with delirium tremens were compared with a group of 13 controls. The controls and patients were hospitalized in order to ensure abstinence from alcohol. The examination of the delirium patients was carried out with their consent after termination of the delirium tremens and again on discontinuance of drug therapy. In the case of 33 delirium patients the absorption of thiamine was tested again 4 weeks after the first examination. RESULTS: The absorption of vitamin B1 was in general only minimally lower in the case of the delirium patients in comparison with the nonalcoholics. The results showed, however, a considerably greater range of scattering of vitamin B1 absorption in the delirium patients. The absorption conditions showed marked improvement in the 4 weeks after delirium. The extent of absorption of vitamin B1 showed no influence on the duration of delirium. The patients with visual hallucinations, however, showed lower thiamine absorption than patients without such symptoms, whereas no dependence of autonomic symptoms on vitamin B1 absorption was seen. CONCLUSIONS: The disturbed absorption conditions in the delirium patients were obvious at the time of the examination as demonstrated by the wide range of absorption values. Improvement or near normal conditions were registered 4 weeks after the delirium. The absorption conditions had possibly already improved during the few days of alcohol abstinence in the course of the delirium treatment. The reduced vitamin B1 absorption of patients suffering from visual hallucination corresponds to observations of alcoholic hallucinosis.