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Biomedical subjects

R E Anderson

Publications and source records attributed to R E Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1995

Stavudine in patients with AIDS and AIDS-related complex: AIDS clinical trials group 089.

In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safety were assessed in 41 patients treated with dosages of 0.5-12.0 mg/kg/day. Among evaluable patients, 10% increases in CD4 lymphocyte counts were sustained in 24 (60%) of 40 during treatment; an NAUC response (normalized area under the CD4 cell count-versus-time curve > 1.0) was observed in 31 (91%) of 34 at 10 weeks and in 20 (80%) of 25 at 24 weeks; 15 (83%) of 18 had decreases in p24 antigenemia; and 24 (60%) of 40 gained > or = 2.5 kg body weight. Median CD4 lymphocyte levels remained above baseline for 6 months in patients receiving > 0.5 mg/kg/day. Median serum p24 antigen levels remained below baseline for > or = 1 year in patients with p24 antigen responses. The principal toxicity was peripheral neuropathy, which generally resolved after drug discontinuation but limited the dosage to < or = 2.0 mg/kg/day. Additional trials assessing the effect of stavudine on overall morbidity and mortality are ongoing.

AIDS-Related Complex↗
PubMed1995

Dose-related activity of stavudine in patients infected with human immunodeficiency virus.

In a multicenter, randomized, open-label, dose-ranging study to determine the relative effects of three dose levels of stavudine on CD4 lymphocyte count, weight gain, and hematologic variables in patients infected with human immunodeficiency virus (HIV), 152 patients with CD4 lymphocyte counts < or = 600/mm3 received stavudine at 0.1 mg/kg/day (n = 51), 0.5 mg/kg/day (n = 53), or 2.0 mg/kg/day (n = 48). The study was designed to evaluate the activity of stavudine after 10 weeks of therapy and permitted extended dosing and follow-up for long-term safety. A significant dose effect on increases in CD4 lymphocyte counts and declines in HIV titer in peripheral blood mononuclear cells was observed. Stavudine was well-tolerated; the only dose-related, dose-limiting adverse event was peripheral neuropathy, which usually was reversible. In this trial, the most favorable therapeutic index was seen at 0.5 mg/kg/day.

Adult↗
PubMed1995

Effect of point-of-use, activated carbon filters on the bacteriological quality of rural groundwater supplies.

The water quality of 24 rural, domestic groundwater supplies treated with point-of-use, powdered activated carbon (PAC) filters was monitored to determine how such treatment might impact the bacteriological quality of private, residential drinking water supplies. Heterotrophic-plate-count (HPC) and total coliform analyses were performed on raw, PAC-treated, and overnight or stagnant (first-draw) PAC-treated water samples. Densities of HPC bacteria were elevated by 0.86 and 0.20 orders of magnitude for spring and well water systems, respectively, in PAC-treated effluents following overnight stagnation compared with levels in untreated treated effluents. Densities of HPC bacteria in PAC-treated effluents were significantly reduced (P < 0.01) below influent levels, however, after the point-of-use device was flushed for 2 min. While PAC significantly reduced the number of coliforms in product waters (P < 0.01), these indicator organisms were still detected in some effluents. Seasonal variations were evident in microbial counts from spring but not well water systems. It appears that aside from periods following stagnant-water use, such as overnight, PAC treatment does not compromise the bacteriological quality of drinking water obtained from underground sources.

Carbon↗
PubMed1995

Effects of intermittent reperfusion on brain pHi, rCBF, and NADH during rabbit focal cerebral ischemia.

BACKGROUND AND PURPOSE: The use of intermittent reperfusion versus straight occlusion during neurovascular procedures is controversial. This experiment studied the effects of intermittent reperfusion and single occlusion on intracellular brain pH (pHi), regional cerebral or cortical blood flow, and nicotinamide adenine dinucleotide (NADH) fluorescence during temporary focal ischemia. METHODS: Twenty fasted rabbits under 1.0% halothane anesthesia were divided into four groups: (1) nonischemic controls, (2) 60 minutes of uninterrupted focal ischemia, (3) 2 x 30-minute periods of focal ischemia separated by a 5-minute reperfusion, and (4) 4 x 15-minute periods of focal ischemia separated by three 5-minute reperfusion periods. Focal ischemia was produced by occlusion of both the middle cerebral and ipsilateral anterior cerebral arteries. After the final occlusion, there was a 3-hour reperfusion period in all groups. Regional cerebral and cortical blood flow, brain pHi, and NADH fluorescence were measured with in vivo panoramic fluorescence imaging. RESULTS: During occlusion, regional cerebral and cortical blood flows and NADH fluorescence values were not different among the groups. Brain pHi was significantly lower in the 4 x 15-minute group compared with the 1 x 60-minute group (6.57 +/- 0.02 versus 6.73 +/- 0.06; P < .03) but not significant when compared with the 2 x 30-minute group. During the short reperfusion periods, all parameters returned to normal except for NADH fluorescence levels, which remained elevated. During the postischemic final reperfusion period, there was a mild brain alkalosis of approximately 7.1 in all groups. There were no significant differences in NADH fluorescence among groups during the final reperfusion. Regional cerebral and cortical blood flow returned to near normal values in all groups. CONCLUSIONS: This study demonstrates that intermittent reperfusion during temporary focal ischemia has different effects on the intracytoplasmic and the intramitochondrial compartments: worsening of brain cytoplasmic pHi but no significant differences in the oxidation/reduction level of mitochondrial NADH.

Animals↗
PubMed1995

Membrane-associated inositol hexakisphosphate binding in bovine retina.

We investigated the InsP6 binding proteins in bovine retinal membranes and rod outer segments (ROS) by radioligand binding assay and western blotting. The relative affinity of InsP6 for the binding protein was determined by competitive binding of [3H]-InsP6 with increasing concentrations of the unlabeled InsP6 or other isomers. InsP6 specifically binds to both bovine retinal membranes and ROS; maximum binding was achieved after one-hour incubation at 4 degrees C and was unchanged up to 2 h. Tris-HCl or acetate buffer was equally suitable for the binding assay over a broad range of pH, although specific binding was slightly increased at acidic pH. The order of potencies of displacement was InsP6 > Ins(1,3,4,5,6)P5 > Ins(1,3,4,6)P4 = Ins(1,3,4,5)P4, whereas Ins(1,4,5)P3, Ins(1,4)P2, Ins(4,5)P2, and Ins(1)P were not effective displacers. Scatchard analyses of the binding data were consistent with an equilibrium dissociation constant (Kd) of 2.5 +/- 0.2 microM and maximal binding capacity (Bmax) of 123.7 +/- 25.0 pmol/mg at pH 7.4. Western blotting was used to detect whether AP-2 (an InsP6 binding protein) is present in the retina. Immunoreactivity to AP-2 alpha and beta subunits was found in retinal membranes and ROS. Thus, bovine retinal membranes and ROS contain membrane-associated InsP6 binding protein(s) which is distinct from proteins that bind InsP5, InsP4, or InsP3.

Animals↗
PubMed1995

Light adaptation of bovine retinas in situ stimulates phosphatidylinositol synthesis in rod outer segments in vitro.

Light-stimulated phosphoinositide turnover has been reported in both vertebrate retina and isolated rod outer segments (ROS). In the current investigation, we examined the incorporation of [3H]-inositol in vitro in bovine ROS isolated from dark adapted (DROS) or bleached (BROS) retinas. Incorporation of [3H]-inositol into phosphoinositides in BROS was 3-5 fold higher than in DROS. The majority (approximately 90%) of [3H]-inositol was found in phosphatidylinositol (PI), whereas phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) accounted for 7-8% of the label. The enhanced labelling of PI was only observed when bovine retinas were light-adapted prior to ROS preparation, suggesting the requirement for an intact photoreceptor for the observed effect. Our data strongly suggest that bleaching of bovine retina in situ stimulates PI synthesis in isolated ROS in vitro.

Adaptation, Ocular↗
PubMed1995

Effect of intermittent reperfusion and nitric oxide synthase inhibition on infarct volume during reversible focal cerebral ischemia.

The authors examined the effects of both intermittent reperfusion and nitric oxide synthase (NOS) inhibition, caused by NG-nitro-L-arginine methyl ester (L-NAME) during episodes of focal cerebral ischemia induced to simulate the neurosurgical setting. Seventy-eight Wistar rats underwent single (60 minutes of ischemia) or repetitive (four 15-minute periods of ischemia separated by 5 minutes of reperfusion) episodes of middle cerebral artery occlusion while under anesthesia (1.0% halothane). Twenty-four hours after the procedure, the animals were given neurological examinations and then sacrificed for histological preparation and examination. The intermittent reperfusion groups tended to have smaller mean cortical infarctions. There was also a trend showing a decrease in infarction size in groups given L-NAME. The combination of intermittent reperfusion and preischemic administration of L-NAME (10 mg/kg) resulted in a 65% reduction in infarction size (p < 0.05) when compared to that caused by 60 minutes of single occlusion without L-NAME. The use of NOS inhibition combined with intermittent reperfusion may be a technique to provide intraoperative cerebral protection during neurovascular procedures that require temporary vascular occlusion.

Analysis of Variance↗
PubMed1994

Basic fibroblast growth factor increases cortical blood flow in vivo.

Basic FGF has recently been shown to produce systemic and cerebral vasodilation. To test the hypothesis that bFGF increases regional cortical blood flow (rCBF), rCBF and brain pHi were measured while bFGF or vehicle was superperfused onto the cortex of rabbits. The results of this study demonstrate that topical application of bFGF causes an increase in rCBF.

Animals↗
PubMed1994

Intracellular and extracellular spaces and the direct quantification of molar intracellular concentrations of phosphorus metabolites in the isolated rat heart using 31P NMR spectroscopy and phosphonate markers.

To quantify metabolite and cation concentrations using NMR spectroscopy, the volumes of intracellular and extracellular spaces must be known. We describe a simple 31P NMR spectroscopic method that employs dimethyl methylphosphonate (DMMP) as a marker of total water space and phenylphosphonate (PPA) as a marker of extracellular space to determine intracellular and extracellular space volumes in the isolated, perfused rat heart. In vivo and in vitro radiolabel studies were used to verify this method. The difference between the total and extracellular water spaces, determined as milliliters/heart, gave the intracellular volume and allowed direct calculation of myocardial creatine phosphate, ATP, and inorganic phosphate concentrations, which were 13.4 mM, 10.1 mM, and 3.4 mM, respectively, for the glucose-perfused rat heart. The extracellular volume decreased by 84% in hearts subjected to 28 min total, global ischemia and increased by 15% during reperfusion. The method described allows the determination of intracellular energy metabolite concentrations in perfused rat heart directly from a single, fully relaxed 31P NMR spectrum.

Animals↗
PubMed1994

Plasma lipid changes in PRCD-affected and normal miniature poodles given oral supplements of linseed oil. Indications for the involvement of n-3 fatty acids in inherited retinal degenerations.

It has previously been shown that miniature poodles with progressive rod-cone degeneration (PRCD) have lower plasma levels of docosahexaenoic acid (22:6n-3) than normal poodles and it has been suggested that affected animals have a defect in the metabolism of 22:6n-3. To test this hypothesis in vivo, PRCD-affected and normal miniature poodles were given daily oral supplements of linseed oil (enriched in 18:3n-3). Blood was drawn from food-deprived animals at predetermined times before, during and after supplementation, and plasma lipid fatty acids were analysed. There were no differences in the levels of 18:3n-3, 20:5n-3, and 22:5n-3 between affected and normal dogs. Therefore, there appears to be no abnormality in the elongation and desaturation system that takes 18:3n-3 to 22:5n-3. Surprisingly, the plasma level of 22:6n-3 was reduced in both groups following supplementation, but to a significantly greater extent in affected dogs. This resulted in a significantly higher 22:5n-3/22:6n-3 ratio in affected animals. These results support the earlier suggestion of an abnormality in 22:6n-3 metabolism in PRCD-affected miniature poodles. To determine the effect of n-3 supplementation on polyunsaturated fatty acid metabolism in dogs (not as a function of disease), results from both groups of dogs were pooled and compared at times before and near the end of supplementation. Dietary 18:3n-3 led to predictable increases in 18:3n-3, 20:5n-3, and 22:5n-3, but to a decrease in 22:6n-3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Free radicals and ocular disease.

Ames, Shigenaga, and Hagen recently published a thorough review of the relationship between oxidants, antioxidants, and degenerative diseases of ageing. They point out that only 9% of Americans daily consume the two fruits and three vegetables recommended by the National Cancer Institute and the National Research Council/National Academy of Science. In addition to antioxidants, these foodstuffs contain many essential micronutrients. To date, specific recommendations for antioxidant supplementation have not been made by any governmental agency or professional association. A number of clinical, basic, and epidemiological studies have implicated free radical induced lipid peroxidation in various ocular disorders. It would seem prudent that those persons at greatest risk for these disorders take some precautions, which could include sunglasses that filter ultraviolet light; hats that shield the eyes from direct sunlight; and the ingestion of fruits, vegetables, and antioxidants.

Aged↗
PubMed1994

A population-based autopsy study of sudden, unexpected deaths from natural causes among persons 5 to 39 years old during a 12-year period.

All unexpected deaths in New Mexico from 1977 to 1988 were reviewed. By statute each such death must be reported to the Office of the Medical Examiner (OMI) and according to institutional policy autopsied even when death is presumed to be from natural causes. From this group the 650 index cases that form the basis of this report were obtained. The crude rate of sudden, unexpected death among New Mexico residents 5 to 39 years old during the study period was 6.6/100,000 persons at risk. As documented by autopsy, the underlying cause of death in a majority of these cases (53.4%) was related to cardiovascular disease and alcoholism. Male persons in general are at increased risk for sudden, unexpected death, and American Indian and black male persons are at greater risk than their Anglo and Hispanic counterparts. American Indians account for a disproportionate share of the unexpected deaths resulting from alcoholism, and black male persons are at particular risk for unexpected death resulting from cardiovascular diseases. This report emphasizes the importance of life style and diet in the well-being of persons 5 to 39 years old.

Adolescent↗
PubMed1994

Cheating by students: findings, reflections, and remedies.

Cheating among students is surprisingly frequent and may be increasing. The 1991 study reported herein was prompted by an episode of cheating involving three second-year medical students at the University of New Mexico School of Medicine (UNM SOM) and was undertaken (1) to elicit the opinions of faculty members and students at that institution about whether selected descriptions of students' behaviors were unethical; (2) to document possible discrepancies between the opinions of the two groups concerning these behaviors; (3) to define the prevalence of unethical behavior among current students as estimated by faculty and students; and (4) to determine how best to approach future instances of unethical behavior. Questionnaires were distributed to all faculty and students. The first two parts, sent to both groups, concerned reactions to a series of described physician and student behaviors. For each described behavior, respondents were asked whether or not it was unethical and, for the described student behaviors, whether they had personal knowledge of such behavior by local medical students. The third portion of the questionnaire concerned faculty perceptions regarding students' behaviors over time. With the exception of the class involved in the cheating incident, faculty and students were surprisingly similar in their opinions regarding the ethical nature of the described behaviors. According to both faculty and students, there was a significant incidence ( > or = to 10% of the respondents) of unethical behavior at the school of medicine, most commonly in relation to cheating on examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude↗
PubMed1994

Immunolocalization of PKC zeta in rat photoreceptor inner segments.

We have utilized several peptide specific antisera directed against the C-terminals (Wetsel et al, 1992) of several protein kinase C (PKC) isozymes (alpha, beta 1, beta 11, gamma, delta, epsilon, zeta) to delineate the cellular localization of these PKC isozymes in rat retina. Antisera against PKC beta 1, beta 11, gamma, delta and epsilon were non-reactive in frozen rat retina sections, whereas, anti PKC alpha was strongly reactive with the outer plexiform, inner plexiform and nerve fiber cell layers. The most specific localization of immunoreactivity was observed with PKC zeta, which reacted strongly and exclusively with photoreceptor inner segments, but not outer segments. Immunoblot analysis of whole rat retina homogenate showed that anti-PKC alpha recognized an antigen of approximately 80kD and anti-PKC zeta recognized a approximately 72kD protein. Immunolocalization of PKC zeta to photoreceptor inner segments and possible functional significance are discussed.

Amino Acid Sequence↗
PubMed1994

Docosapentaenoic acid is converted to docosahexaenoic acid in the retinas of normal and prcd-affected miniature poodle dogs.

PURPOSE: Docosahexaenoic acid (DHA, 22:6n-3) is the major fatty acid of photoreceptor membranes that is necessary for optimal retinal function. Miniature poodle dogs with progressive rod-cone degeneration have lower plasma levels of DHA than normal dogs and higher 22:5n-3/22:6n-3 ratios. The purpose of this study was to test the hypothesis that the metabolic defect in dogs affected with progressive rod-cone degeneration was a reduced capacity for ocular synthesis of DHA from its precursor 22:5n-3. METHODS: The in vivo retinal conversion of [14C]22:5n-3 to [14C]22:6n-3 was investigated by injecting normal dogs and dogs affected with progressive rod-cone degeneration intravitreally with [14C]22:5n-3. After 72 hours, rod outer segments, remaining retina, and retinal pigment epithelium/choroid were analyzed for metabolic products. RESULTS: Using high-performance liquid chromatography, six radioactive peaks were detected in both normal and affected dogs: [14C]20:5n-3, [14C]22:6n-3, [14C]22:5n-3, [14C]24:6n-3, [14C]24:5n-3, and [14C]18:0. The majority of the label in each tissue was in 22:6n-3 and there was no difference in the dpm% of [14C]22:6n-3 in normal and affected animals in any of the three tissues. Voss et al (J Biol Chem 1991;266:19995-20000) proposed a new pathway for the synthesis of DHA that involves elongation of 22:5n-3 to 24:5n-3, desaturation to 24:6n-3, and beta-oxidation to 22:6n-3. Identification of the products [14C]24:5n-3 and [14C]24:6n-3 verified that these putative intermediates are present in the dog retina. CONCLUSIONS: The finding of large amounts of label in DHA shows that the normal and progressive rod-cone-degenerated retina and retinal pigment epithelium are capable of DHA synthesis from 22:5n-3. The presence of radioactivity in 24:5n-3 and 24:6n-3 suggests that the synthesis of DHA in the retina is similar to that described in the liver.

Animals↗