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Biomedical subjects

R Eng

Publications and source records attributed to R Eng.

At least 19 recordsLinked to original sources

Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group.

BACKGROUND: Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. METHODS: We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months. RESULTS: Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001). CONCLUSIONS: Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

AIDS-Related Opportunistic Infections↗

Mechanisms of cyclic nucleotide-induced relaxation in canine tracheal smooth muscle.

The effects of exogeneous cyclopiazonic acid (CPA, 10 microM), a selective inhibitor of the sarcoplasmic reticulum (SR) Ca2+ adenosinetriphosphatase, on cyclic nucleotide-induced relaxations of canine airway smooth muscle were examined. Strips of tracheal muscle were precontracted with carbachol (50% median effective concentration, 0.1 microM) or with 60 mM KCl. The beta-agonist isoproterenol (ISO, 10 microM) relaxed the tissue by approximately 50%. The relaxation was reduced in the presence of CPA when L-type Ca2+ channels were available but not when these were blocked by 0.1 microM nifedipine. Forskolin (1.0 microM), an adenylate cyclase activator, was less effective at inhibiting the contraction than ISO, and addition of CPA did not block its inhibitory effect as effectively as when ISO was used. Radioimmunoassay indicated that both these agents raised adenosine 3',5'-cyclic monophosphate (cAMP) levels to the same degree. Very little relaxation of the precontracted smooth muscle was elicited by 3 mM 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP), and addition of CPA had no effect. Sodium nitroprusside (100 microM) and 8-bromo-guanosine 3',5'-cyclic monophosphate (10 mM) inhibited contraction to a greater degree than any agent that raised cAMP. These inhibitions were greatly reduced in the presence of CPA when L-type Ca2+ channels were available. We conclude that pumping of Ca2+ into SR plays a major role guanosine 3',5'-cyclic monophosphate-produced but not cAMP-induced relaxation; L-type Ca2+ channels must be available for the relaxant role of Ca2+ pumping into the SR to be expressed; and ISO-induced relaxation may not involve primarily elevation of the cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

The differential effect of cigarette smoke on the growth of bacteria found in humans.

The effect of cigarette smoke on growth of those species of bacteria that are considered common potential human pathogens was examined in vitro. Smoke from both mentholated and nonmentholated cigarettes inhibited the growth of Gram-positive cocci to a greater degree than that of Gram-negative rods. Staphylococcus aureus, Streptococcus pneumoniae, and a variety of other streptococci were inhibited at a smoke solution dilution of 1:8. Enteric bacteria such as Klebsiella, Enterobacter, and Pseudomonas were not affected by a 1:1 dilution of the solution. As with the Gram-positive cocci, the Neisseria species and Branhamella were also inhibited at a dilution of 1:8. Culture results of the mouth of 15 smokers and 15 nonsmokers showed that the smokers have a propensity to develop heavy Gram-negative bacterial colonization.

Bacteria↗

Liposuction in cervical rejuvenation.

Superficial musculoaponeurotic system (SMAS) has represented a confusing anatomical structure because descriptions of it in classical treatises of anatomy are contradictory. Also, utilization of this system in facial rejuvenation also does not coincide with the true anatomical facts regarding the superficial musculo-aponeurosis. A macroscopic and histological study of the region was carried out in order to determine the areas of fat deposits and the distribution of the true cervical superficial aponeurosis, partly in accordance with the statements by Jost and leaving aside the concept proposed by Mitz and Peyronie. Cervical liposuction was combined with the techniques for cervicofacial rhytidectomy.

Adipose Tissue↗

Cloning and tissue-specific expression of mouse macrophage colony-stimulating factor mRNA.

Macrophage colony-stimulating factor (CSF-1) stimulates the production of macrophages from bone marrow progenitor cells. We have identified a cDNA clone for murine CSF-1 by antibody screening of a mouse L-cell cDNA library in the expression vector lambda gt11. A screen of about 150,000 recombinant plaques yielded 6 clones that reacted well with an antibody raised against denatured and reduced mouse L-cell CSF-1. These clones were further screened with synthetic oligonucleotides based on the amino-terminal amino acid sequence of CSF-1. One clone, which hybridized to the oligonucleotides, was sequenced and found to contain a single open reading frame. This encompassed 68 amino acids of the mature protein, including the entire amino-terminal sequence we previously reported. This is preceded by what appears to be a 31 amino acid signal peptide. Blot analysis showed that this cDNA hybridizes to a major mRNA species of about 4.5 kilobases (kb) as well as several smaller, less abundant mRNA species (3.8, 2.3, and 1.4 kb) present in mouse L cells. A similar pattern of hybridization was observed with mRNA from a human pancreatic carcinoma cell line that produces CSF-1. Striking differences in the qualitative and quantitative expression of mRNA species for CSF-1 were observed in various mouse tissues. Liver expressed primarily a 1.4-kb species, heart and lung expressed primarily a 4.5-kb species, brain expressed high levels of both the 4.5-kb and 1.4-kb species, and intestine lacked detectable CSF-1 transcripts. Southern blot analysis suggests that the CSF-1 gene is present as a single copy in the mouse haploid genome and that it is not rearranged or amplified in L cells.

Amino Acid Sequence↗

Receptor-selective localization in pancreas.

We examined the distribution of three tritiated ligands and two radioiodinated ligands for their ability to localize in the pancreas of rat and rabbit. The ligands examined are selective for the alpha- and beta-adrenoceptors and the muscarinic acetylcholine receptor. Of the ligands examined, the results indicate that only (R) 3H-3-quinuclidinyl benzilate (QNB) localized in the pancreas by the receptor-mediated mechanism. The % dose/g tissue, the pancreas-to-blood and pancreas-to-liver ratios are such that a 18F-labeled derivative of QNB should provide images of the pancreas.

Adrenergic beta-Antagonists↗

Use of 3-quinuclidinyl 4-iodobenzilate as a receptor binding radiotracer.

3-Quinuclidinyl 4-iodobenzilate was shown to bind to the muscarinic acetylcholine receptor (mAChR) by testing the saturability and the stereoselectivity in the corpus striatum, cerebellum, and the heart. But the ratio of radioactivity in tissues containing different concentrations of mAChR was less than the ratio of mAChR concentrations determined by in vitro saturation assay. As a result, the sensitivity to change in receptor concentration by external imaging will be reduced for this receptor binding radiotracer.

Animals↗

External imaging of cerebral muscarinic acetylcholine receptors.

A radioiodinated ligand that binds to muscarinic acetylcholine receptors was shown to distribute in the brain by a receptor-mediated process. With single-photon-emission imaging techniques, radioactivity was detected in the cerebrum but not in the cerebellum, whereas with a flow-limited radiotracer, radioactivity was detected in cerebrum and cerebellum. Single-photon-emission computed tomography showed good definition of the caudate putamen and cortex in man.

Animals↗

In vivo competition studies with analogues of 3-quinuclidinyl benzilate.

Among ligands that bind to the alpha- and beta-adrenoceptors and to the muscarinic acetylcholine receptor (m-AChR), those that bind to the latter have the best properties for external detection of receptor sites by gamma-camera imaging. To develop the optimal radiotracer, nonradioactive analogues of 3-quinuclidinyl benzilate (I) were tested in in vivo displacement studies with (-)-[3H]I to determine their ability to compete with (-)-[3H]I for the muscarinic acetylcholine receptor. There is a linear correlation between the ability to compete with (-)-[3H]I for the m-AChR and the affinity constant of the analogue as determined by in vitro assay, suggesting that the test is a valid indicator of in vivo distribution. One radioiodinated analogue, 3-quinuclidinyl p- iodobenzilate , bound to m-AChR in the heart and brain of rats.

Animals↗

Drug-resistance encountered in the retreatment of Mycobacterium tuberculosis infections.

Patients who had prior anti-tuberculosis medications for pulmonary tuberculosis and who return to the hospital with culture-positive tuberculosis have been considered to be at risk of harboring resistant bacilli (secondary resistance or acquired resistance). The present recommendation for therapy of these patients is to resume earlier anti-tuberculosis medications and to add two new agents until the drug susceptibilities of the bacilli are known. This study reviewed 112 cases of readmissions for active tuberculosis and evaluated the risk of acquired drug resistance in this group. Patients with 6 months or less of prior therapy rarely harbored resistant organisms. Patients with 6-12 months of prior therapy had an 88% possibility of harboring resistant bacilli, but only a 30% risk of harboring multiple-drug resistant bacilli. Patients with 12 months or more of prior therapy had a 66% risk of harboring multiple-drug resistant, difficult-to-treat bacilli. This data would indicate that only those patients who have had prior therapy for 7 months or more require aggressive initial readmission therapy with 4 or more anti-tuberculosis agents. Hopefully this finding will not only help clinicians to identify readmission tuberculosis patients who are at increased risk of harboring resistant organisms but will also help them to be more selective in prescribing aggressive, potentially toxic, multiple-drug regimens.

Aminosalicylic Acid↗

Preoperative latent place learning preserves salt appetite following damage to the central gustatory system.

Rats given the experience of tasting saline before receiving lesions in the region of the thalamic taste relay are protected from the usual lesion-induced deficits in salt appetite. In this study, the location of the saline during postoperative testing was varied from the location during preoperative training for some rats, and it was kept the same for others. A clear protective effect was evident when the preoperative and postoperative location was the same but not when it was different. This protective effect may be due to place learning, because it is known that rats can remember tasting saline in a particular place and then return there when in a state of sodium need.

Animals↗

Pathogenicity of Eikenella corrodens in humans.

Eikenella corrodens is resident flora of the normal adult human oral cavity. Four cases of verified infection and previous case reports of infections caused by this organism were reviewed and analyzed. Rarely has this bacillus been found as the sole isolate to initiate infection in the host with normal immune status. In the immunocompromised host, this organism was observed as the sole isolate in cases of persistent empyemas and/or overwhelming pneumonias with bacteremias. The potential of the organism singly to perpetuate an established infection appears real. In the immunocompromised patients such potentials are accentuated and can result in fulminant pulmonary infections and death. The finding of E corrodens in an infection site of a compromised patient should indicate specific therapy.

Aged↗

Polydipsia and abolition of angiotensin-induced drinking after transections of subfornical organ efferent projections in the rat.

Rats with transections of subfornical organ (SFO) efferent projections failed to drink to intravenous angiotensin-II (AII) but responded to intracellular dehydration and water deprivation and suppressed drinking when food deprived. However, the transected rats were polydipsic and polyuric. Thus SFO efferent projections mediate AII-induced drinking and may be involved in the regulation of body fluid balance.

Angiotensin II↗

Vagal mediation of hypothalamic obesity but not of supermarket dietary obesity.

In two independent experiments, complete subdiaphragmatic vagotomy did not prevent the development of the obesity that results from the addition of highly palatable foods to the diet of rats. The vagotomized animals exhibited only a 1-day delay in the onset of overeating, and this only when first exposed to the tasty diet. In independent tests of the functional completeness of the vagotomies, the vagotomized animals failed to overeat or gain excessive weight on a standard laboratory diet following bilaterally parasagittal hypothalamic knife cuts. Thus, hypothalamic knife-cut obesity requires the integrity of the vagus for its full expression, whereas dietary obesity does not.

Animals↗