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Biomedical subjects

A C White

Publications and source records attributed to A C White.

At least 73 records · Page 4Linked to original sources
PubMed1995

Intestinal function and injury in acquired immunodeficiency syndrome-related cryptosporidiosis.

BACKGROUND/AIMS: The pathogenesis of the diarrhea in acquired immunodeficiency syndrome (AIDS)-related cryptosporidiosis is not known. The hypothesis of this study was that the intestinal dysfunction and injury are related to the number of organisms infecting the intestinal mucosa. The aim of this study was to study the influence of intensity of infection on intestinal function and injury in AIDS-related cryptosporidiosis. METHODS: In 16 patients with AIDS with intestinal Cryptosporidium infection, the intensity of infection was quantified by counting the total number of fecal oocysts excreted in 24 hours and by determining the percent of duodenal epithelium covered by organisms. Intestinal function was assessed by vitamin B12 absorption and serum D-xylose test. Intestinal injury was assessed by morphology of duodenal mucosa, differential urinary excretion of lactulose and mannitol, and fecal alpha 1-antitrypsin clearance. Measurements were repeated after treatment with paromomycin. RESULTS: Vitamin B12 and D-xylose absorption negatively correlated with intensity of infection. Villus atrophy occurred only in patients with oocyst excretion of > 10(8) oocyst/24 hours. Lactulose/mannitol urinary excretion ratio showed a positive correlation with intensity of infection. Intestinal function and injury improved in patients whose oocyst counts were reduced by treatment with paromomycin. CONCLUSIONS: Cryptosporidium infection in patients with AIDS causes malabsorption and intestinal injury in proportion to the number of organisms infecting the intestine.

AIDS-Related Opportunistic Infections↗
PubMed1995

Adjuvant activity of QS-21 for experimental E. coli 018 polysaccharide vaccines.

Three types of experimental vaccines containing O-side-chain polysaccharide from the enterotoxigenic strain Escherichia coli 018 were evaluated. The immunogenicity of free O-polysaccharide (PS), a polysaccharide-diphtheria toxoid conjugate (PS-conj), and detoxified lipopolysaccharide (dLPS) was tested in female ICR mice, either alone or in combination with QS-21, a purified saponin adjuvant derived from the bark of the tree Quillaja saponaria Molina. Both the number of individual mice responding and the titres of O-polysaccharide specific antibodies in pools of sera were increased by the addition of QS-21. The immune response to both O-specific polysaccharide and carrier was primarily IgM and IgG1. The addition of QS-21 not only increased the level of IgG1, but also had a significant adjuvant effect on antigen-specific IgG2a, IgG2b and IgG3.

Adjuvants, Immunologic↗
PubMed1995

Lack of correlation between diarrhea and weight loss in HIV-positive outpatients in Houston, Texas.

To determine the prevalence of diarrhea and weight loss among human immunodeficiency virus (HIV)-positive patients, we reviewed the records of all patients attending the Harris County HIV Clinic during a 4-month time period. Diarrhea was considered persistent if it had been present for > 14 days or on two or more consecutive clinic visits. Weight loss was defined as moderate (5-10% reduction in weight) or severe (> 10% reduction) when the present weight was compared with the weight found at the initial clinic visit. Records were reviewed for 1,370 patients, of whom 12.2% complained of diarrhea (7.7% acute and 4.5% persistent). Diarrhea was more common among patients with a history of male-to-male sexual contact than in patients with other HIV risk factors (p < 0.003 for acute and p < 0.006 for persistent). The mean CD4 cell count was not significantly different in patients with or without persistent diarrhea (176 versus 212) or acute diarrhea (215 versus 212). Weight loss was reported in 25.2% of subjects (12.8% moderate and 12.4% severe). It did not correlate with CD4 count. Persistent diarrhea also was not associated with weight loss. Acute and persistent diarrhea were common among ambulatory HIV-positive patients, particularly in homosexual men. We did not identify a correlation among diarrhea, weight loss, and CD4 count. Thus, factors other than chronic diarrhea and immunosuppression appear to be responsible for weight loss in HIV-infected patients.

Acute Disease↗
PubMed1995

Effect of nitric oxide and cell redox status on the regulation of endothelial cell xanthine dehydrogenase.

We have previously reported that endothelial cell (EC) xanthine dehydrogenase/xanthine oxidase (XD/XO) activity correlates inversely with the O2 tension to which the cells are exposed. Whether this effect is related to the production of reactive O2 species is unclear. We exposed bovine pulmonary artery EC to various conditions that altered the redox status of the cells: 1) hypoxia (3% O2) and normoxia (20% O2); 2) menadione (MEN), known to generate O2 radicals; 3) catalase (CAT) and reduced glutathione (GSH), which detoxify H2O2; and 4) various NO-generating systems. Changes in intracellular XO and XO + XD activities were correlated with rates of extracellular H2O2 release from the same cells. Conditions that decreased extracellular H2O2 release (hypoxia, CAT, and GSH) produced significant and parallel increases in intracellular XO and XO + XD activities in a time-dependent fashion. MEN treatment increased extracellular release of H2O2 and subsequently reduced intracellular XO and XO + XD activities. NO-generating agents did not change extracellular release of H2O2 but significantly reduced XO and XO + XD activities. The latter effect was prevented by reduced hemoglobin. Scavengers of hydroxyl radicals reversed the inhibition of XO and XO + XD activities produced by MEN but not that produced by NO. While NO significantly inhibited XD/XO activity from rat epididymal fat pad, it did not affect XD/XO mRNA expression in these cells. We conclude that intracellular XD/XO activity is sensitive to changes in oxidant-generating and protective systems. Inhibition of XD/XO activity by NO may be mediated through direct binding of NO to the enzyme iron-sulfur moiety or to its sulfhydryl groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Decreased dihydropyridine receptor number in hypertensive rat vascular muscle cells.

To further investigate the altered function of Ca2+ channels in vascular muscle cells in hypertension, a novel fluorescently labeled dihydropyridine was used with ultrahigh-sensitivity photometry to study dihydropyridine binding sites on the surface membrane of living vascular muscle cells from stroke-prone spontaneously hypertensive rats and their normotensive controls. Fluorescent nitrobenzoxadiazol-6-dihydropyridine in concentrations of 1 to 100 nmol/L bound specifically to vascular muscle cells' Ca2+ channels, and was displaced by the unlabeled dihydropyridine analogue or nisoldipine (10 mumol/L). Stroke-prone spontaneously hypertensive rat vascular muscle cells showed significantly decreased binding of nitrobenzoxadiazol-6-dihydropyridine compared with normotensive National Institutes of Health rats. Decreased binding of dihydropyridine by vascular muscle cells from stroke-prone spontaneously hypertensive rats (cells that in other studies show increased Ca2+ channel function) indicates a change in channel regulation that is possibly due to a deficiency in the inactivation mechanism, consistent with our earlier electrophysiological studies reporting deficiencies in Ca(2+)-dependent inactivation in genetic hypertension. These data demonstrate decreased numbers of localized sites of dihydropyridine binding on the sarcolemma of living vascular muscle cells, and support the hypothesis that Ca2+ channel alterations may significantly contribute to the molecular etiology of genetic hypertension.

4-Chloro-7-nitrobenzofurazan↗
PubMed1995

Nitric oxide increases cellular glutathione levels in rat lung fibroblasts.

Nitric oxide (NO) has been demonstrated to play a protective role in cell injury. In this study, we have explored the effect of NO and two NO donors (sodium nitroprusside [SNP] and isosorbide dinitrate [ISDN]) on cellular glutathione (GSH) levels in a rat lung fibroblast cell line (RFL6 cells). SNP and ISDN significantly increased cellular GSH in RFL6 cells (5 x 10(-4) M SNP: 21.9 +/- 3.6 nmol/10(6) cells and 5 x 10(-3) M ISDN: 27.6 +/- 1.7 nmol/10(6) cells versus control: 13.2 +/- 0.4 nmol/10(6) cells; P < 0.05). The stimulatory effect of SNP and ISDN on GSH was first seen at 6 h and peaked at 12 to 24 h. A similar increase in GSH was observed in RFL6 cells exposed to 400 ppm NO for 7.5 h (NO: 20.5 +/- 3.4 nmol/10(6) cells versus control: 11.9 +/- 2.4; P < 0.05). SNP and ISDN also increased cellular GSH in bovine pulmonary artery smooth muscle cells (BPSMC) and bovine pulmonary artery endothelial cells (BPAEC). Buthionine sulfoximine (BSO) (0.01 mM), an inhibitor of the GSH synthetic enzyme gamma-glutamyl cysteine synthetase, blocked the increase in GSH in RFL6 cells seen with both SNP and ISDN. In BPAEC, exposure to NO donors for 24 h stimulated glutamate uptake (SNP: 441 +/- 19 pmol/10 min/10(6) cells and ISDN: 677 +/- 48 pmol/10 min/10(6) min/10(6) cells versus control: 222 +/- 9 pmol/10 min/10(6); P < 0.05). This effect paralleled the increase in GSH. In RFL6 cells, only SNP increased glutamate uptake after 24 h of incubation. In summary, NO and NO donors increase cellular GSH in RFL6 cells, BPAEC, and BPSMC. The mechanism of this effect is unclear but may involve upregulation of the normal GSH synthetic pathways. This observation may explain in part the protective effect of NO seen in some cell culture systems and may contribute to a protective effect against oxidant injury in vivo.

Animals↗
PubMed1995

Suicide by self-strangulation whilst under observation.

Two cases are reported of individuals who committed suicide after they had been identified as being acutely at risk of killing themselves. Self-strangulation by a ligature fashioned from the subjects' clothes was the mechanism of suicide in both cases. One death occurred in a police station and the other on an acute psychiatric ward. These cases highlight the need for those formulating policies concerning the supervision of the suicidal individual to pay attention to the minutiae of detail. In particular, a case is made for those at risk of suicide to be prevented from sleeping with their head covered by blankets.

Adult↗
PubMed1994

Evaluation of [O-methyl-3H]WAY-100635 as an in vivo radioligand for 5-HT1A receptors in rat brain.

N-(2-(4-(2-Methoxyphenyl)-1-piperazinyl)ethyl)-N-(2- pyridyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) is a new, potent and selective 5-HT1A receptor antagonist. We have evaluated radiolabelled WAY-100635 as a prospective radioligand for positron emission tomography (PET) by studying biodistribution in rat ex vivo. After intravenous injection, [O-methyl-3H]WAY-100635 cleared rapidly from plasma but was retained in brain. Specific binding was quantified from kinetic studies, using a reference-tissue compartment model, fitting for binding potential (k3/k4). The regional variation in binding potential correlated with the known distribution of 5-HT1A receptors. Saturation studies gave Bmax values in vivo that were consistent with those reported in vitro. At 60 min after injection, the ratio of radioactivity in 5-HT1A receptor-rich regions (e.g. septum, entorhinal cortex and hippocampus) to that in cerebellum reached approximately 16. Pre-dosing the rats with WAY-100635 (2 mg/kg) reduced this ratio to one, whereas similar pre-dosing with citalopram (5-HT uptake site inhibitor), prazosin (alpha 1A-adrenoceptor antagonist) or idazoxan (alpha 2-adrenoceptor antagonist) caused little or no reduction. Substantial (77%) blockade of [3H]WAY-100635 binding was achieved with the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the partial agonists, ipsapirone and buspirone. Thus, the properties of WAY-100635 are such that, when labelled with carbon-11, it could provide a radioligand suitable for clinical and pharmacological investigations of central 5-HT1A receptors in man using PET.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Imported malaria in the 1990s. A report of 59 cases from Houston, Tex.

OBJECTIVE: To determine the frequency, the clinical features, and the response to therapy of imported malaria that was diagnosed in the 1990s in a major North American city. METHOD: A retrospective case series from Houston, Tex, of 59 cases of imported malaria presenting between January 1990 and April 1993. RESULTS: Malaria was diagnosed in 59 patients, consisting of 12 cases among patients who had acquired the infection while they were living in endemic areas prior to immigration to the United States, 32 cases among US residents who were originally from endemic areas, and 15 cases among patients originally from North America or Europe. Only 12 patients had received malarial prophylaxis: eight with chloroquine, one with chloroquine and chloroguanide (proguanil), two with chloroquine and primaquine, and one with mefloquine taken intermittently. Eight presented with Plasmodium falciparum infection after receiving chloroquine, and one, after receiving chloroquine and chloroguanide. Two presented with malaria caused by Plasmodium vivax despite receiving chloroquine and primaquine as prophylaxis. In 25 cases, malaria was not considered as an initial diagnosis. Five patients presented with severe disease (three with severe hemolysis, two each with cerebral malaria and renal failure, and one with adult respiratory distress syndrome). Four of the five had initially received a misdiagnosis. Two patients died despite treatment with intravenous quinidine and exchange transfusions. Two patients with P vivax infection had multiple relapses despite courses of chloroquine and primaquine. Six patients were pregnant (including one with a fatal case), one congenital infection was identified. Six patients had not traveled outside of the United States in over 1 year. CONCLUSION: Imported malaria occurs frequently and usually results from the failure to use appropriate prophylaxis. Delayed diagnosis and misdiagnosis are common. Severe disease and fatal cases continue to be seen despite aggressive treatment. Drug resistance has continued to spread and now occurs with P vivax as well as P falciparum.

Adult↗
PubMed1994

Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial.

To test the effects of paromomycin, 10 patients with AIDS and cryptosporidiosis were randomized to paromomycin or placebo in a double-blind trial. After 14 days, patients were switched to the other treatment for 14 additional days. Measures included the number and character of each stool and weekly 24-h stool specimens for weight and oocyst excretion. During the paromomycin treatment phase, oocyst excretion decreased from 314 x 10(6) to 109 x 10(6)24 h (P < .02). Oocyst excretion increased for the 4 patients initially on placebo compared to a median decrease of 128 x 10(6)/24 h for the 6 initially treated with drug (P < .02). Stool frequency also decreased more in those treated with drug (3.6 fewer vs. 1.25 fewer/24 h, P < .05). Trends favored drug over placebo for stool weight, stool character, and Karnofsky score. Paromomycin treatment resulted in improvement in both clinical and parasitologic parameters in cryptosporidiosis in AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1994

Neurocysticercosis in Houston, Texas. A report of 112 cases.

Neurocysticercosis (NCC) is a common disease among Hispanic immigrants to the American Southwest. The experience in this series suggests a higher incidence of disease than has been reported by public health personnel. Symptoms at presentation correlate with the anatomic site of disease. Parenchymal disease and inactive calcifications present primarily with seizures; ventricular disease with headaches and symptoms of acute hydrocephalus; and cisternal disease with basilar meningitis, hydrocephalus, or seizures from coexisting parenchymal disease. Current treatment regimens are suboptimal, although symptoms may resolve in the absence of therapy. Patients may not respond to a single course of praziquantel therapy. Procedures to divert cerebrospinal fluid are often needed and frequently require revision. We found an association between corticosteroid treatment and the need for repeat therapy with praziquantel, but controlled studies are needed to clarify the role of antiparasitic agents in all forms of neurocysticercosis.

Adolescent↗
PubMed1993

Duodenal morphology and intensity of infection in AIDS-related intestinal cryptosporidiosis.

BACKGROUND: The pathogenesis of intestinal cryptosporidiosis is not known. Previous studies have shown that the intensity of infection varies between patients. The hypothesis of this study is that intestinal injury is related to the intensity of infection. METHODS: The histological abnormalities associated with Cryptosporidium infection were evaluated in duodenal biopsy specimens from 18 patients with acquired immunodeficiency syndrome-associated cryptosporidiosis. The intensity of Cryptosporidium infection was assessed histologically in all patients as the percentage of mucosa covered by organisms and by quantitation of oocyst excretion in the stools of 14 patients. RESULTS: Duodenal biopsy specimens from 13 patients (72%) showed normal villous architecture. In these patients, the inflammatory component of the lamina propria was either normal or moderately increased. This increase consisted mostly of lymphocytes and plasma cells. Five of 18 patients (28%) had flattening of the mucosa associated with a prominent neutrophilic infiltrate. The intensity of infection in patients with villous flattening as measured from biopsy specimens and stool was significantly higher than in those without flattening (92% vs. 12% mucosa occupied with organisms; 738 x 10(3) vs. 199 x 10(3) oocyst/mL stool) (P < 0.004 in both cases). CONCLUSIONS: Most patients with intestinal Cryptosporidium infection had normal duodenal villous architecture. Severe duodenal morphological abnormalities, including flattening of the villi, were associated with high-intensity infections.

AIDS-Related Opportunistic Infections↗
PubMed1993

Loa loa infection as a cause of migratory angioedema: report of three cases from the Texas Medical Center.

Loa loa is a filarial parasite that is endemic in West and Central Africa. Expatriates infected with L. loa commonly develop characteristic migratory angioedema called Calabar swellings. We describe three patients who presented with classical Calabar swellings for whom the diagnosis of loiasis was delayed. Unusual features that were present included a leukocytoclastic vasculitis seen on skin biopsy (case 1), a relatively short exposure to an area of endemicity (cases 1 and 3), and a normal eosinophil count on initial evaluation (cases 2 and 3). We discuss the characteristic clinical manifestations of, pathological findings of, and therapy for loiasis. With the increased frequency of international travel, L. loa infection must be considered in the differential diagnosis for patients with migratory angioedema, urticarial vasculitis, or eosinophilia.

Adult↗