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Biomedical subjects

M Armstrong

Publications and source records attributed to M Armstrong.

At least 19 recordsLinked to original sources
PubMed1992

Mutant debrisoquine hydroxylation genes in Parkinson's disease.

The frequency of fifteen genotypes of CYP2D6 (debrisoquine 4-hydroxylase) in 53 patients with Parkinson's disease was determined by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses and compared with the findings in 72 healthy controls. The commonest mutant allele, CYP2D6B, was twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.70 (95% confidence interval 1.14-6.41; p = 0.0063) for subjects homozygous or heterozygous for this allele.

Aged↗
PubMed1992

Sinusitis in HIV-infected patients: a clinical and radiographic review.

PURPOSE: To describe the clinical, radiographic, and laboratory features of sinus disease in human immunodeficiency virus (HIV)-infected individuals. PATIENTS: Seventy-two patients with a history of sinusitis identified from 1,461 consecutive admissions (667 patients) to the HIV ward at The Johns Hopkins Hospital. METHODS: Retrospective chart review. SETTING: The Johns Hopkins Hospital. RESULTS: Sinusitis was identified in 72 HIV-infected patients, predominantly individuals with a CD4 cell count of less than 200/mm3. A history of respiratory infections such as bacterial pneumonia, bronchitis, and otitis media was common. Although nasal congestion and postnasal drainage were found in the majority of patients, symptoms of sinusitis were often nonspecific and the diagnosis was incidental in 28 patients (33%). Magnetic resonance imaging or computed tomography was significantly more sensitive than plain radiography (p less than 0.001) in defining the extent of the disease, particularly with posterior sinus involvement, which occurred in the majority of the patients. The number of radiologically abnormal sinuses correlated inversely with the CD4 count. Although the majority of patients responded at least partially to antibiotic therapy, only 15% had complete resolution of clinical symptoms. Fifty-eight percent of patients had clinical and/or radiographic evidence of recurrent/persistent sinus infection, and chronicity correlated with a CD4 count less than 200/mm3 (p less than 0.001). CONCLUSIONS: Sinusitis in HIV-infected patients is common, severe, and difficult to treat. Patients with CD4 counts less than 200/mm3 are prone to disease involving multiple sinuses that responds incompletely to antibiotic therapy, often resulting in chronic sinusitis. Unlike the immunocompetent host, the majority of the HIV-infected patients with advanced immunodeficiency develop posterior sinus disease.

Adult↗
PubMed1992

The pharmacogenetics of chemical carcinogenesis.

The human body is endowed with a large number of xenobiotic chemical metabolizing enzymes, a significant proportion of which are polymorphic and thus render one individual at greater or lesser risk than another of chemically-induced disease. All examples of genetic polymorphism of chemical metabolizing enzymes have been reviewed in relation to their potential to activate and detoxicate procarcinogens and promutagens. Many examples are cited whereby phenotype can act as a carcinogenic risk factor. With the availability of a large amount of DNA sequence data for chemical metabolizing enzymes there has emerged a number of polymerase chain reaction (PCR) strategies aimed at discerning one metabolic phenotype or another. This is seen as a very positive and democratic scientific development, widening the franchise for studies of disease risk. Nevertheless, it is argued that, at these early stages with many laboratory-based scientists scarcely familiar with epidemiological study design, a cautious approach should obtain when interpreting single studies.

Animals↗
PubMed1991

AIDS in Africa.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Genetic and metabolic criteria for the assignment of debrisoquine 4-hydroxylation (cytochrome P4502D6) phenotypes.

A randomly selected population of 73 volunteers, together with 22 previously established poor metabolisers of debrisoquine, were phenotyped for their ability to 4-hydroxylate debrisoquine and were also analysed for a number of mutations in the CYP2D6 gene. Genotyping was performed using both restriction fragment length polymorphism with the restriction enzyme Xba I, together with two separate polymerase chain reaction assays. Together, these assays detected 98% of mutant alleles in the poor metaboliser group which corresponded to positive identification of 95% of this group. The most common mutant allele detected as the 29B which comprised 75% of total alleles in the poor metaboliser group, whereas the 29A had a frequency of 0.11. Two other allelic variants, which were detectable by restriction fragment length polymorphism analysis occurred at frequencies of 0.07 and 0.05. In the volunteer group, 2.7% of subjects were genotypically poor metabolisers, 35.6% heterozygous extensive metabolisers and 61.7% homozygous extensive metabolisers, on the basis of the genotyping assays used. A good correlation between debrisoquine metabolic ratio and genotype was obtained particularly for subjects genotyped as homozygous extensive metabolisers.

Alleles↗
PubMed1990

AIDS dementia complex: brain high-energy phosphate metabolite deficits.

To test whether compromised high-energy phosphate metabolism is implicated in the neurologic impairment of acquired immunodeficiency syndrome dementia complex (ADC), brain phosphate metabolite concentrations and ratios were measured noninvasively in 12 patients with mild to moderate ADC and 29 healthy volunteers by use of localized phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) magnetic resonance (MR) imaging. In patients, brain phosphocreatine (PCr) and nucleoside triphosphate (NTP) concentrations in sections through the centrum semiovale that were seen with NMR spectroscopy were reduced significantly from normal values of 4.92 mmol/kg wet weight +/- .13 (standard error of the mean) and 2.79 mmol/kg +/- .11, respectively, to 3.33 mmol/kg +/- .26 and 1.99 mmol/kg +/- .13 (P less than .0001). The ratios of metabolites detectable with P-31 NMR spectroscopy did not differ significantly from those of control subjects. The magnitude of the PCr and NTP deficits in ADC was not explicable by focal abnormalities or cerebral atrophy quantified in images of the same regions. These results are consistent with the hypothesis of a generalized virus-associated toxic process affecting brain cell function in ADC. Noninvasive measurement of metabolite concentrations with NMR spectroscopy provides new functional information that may help quantify disease progression and response to therapy.

AIDS Dementia Complex↗
PubMed1990

Effect of pentoxifylline on the flow of polymorphonuclear leukocytes through a model capillary.

Pentoxifylline is a methylxanthine derivative used to increase blood flow in peripheral atherosclerosis. Pentoxifylline is known to increase whole blood filtration rate, and recent evidence suggests that pentoxifylline increases the filtration rate of polymorphonuclear leukocytes (PMNs). The purpose of this study was to directly observe and quantitate the effect of pentoxifylline on the flow of individual PMNs into a model capillary. Short-term incubation of human PMNs with 10 mM pentoxifylline inhibited cell activation, as judged by a significant reduction in the number of neutrophils forming pseudopods. Furthermore, incubation of PMNs from 6 healthy men with 0.1, 1.0 and 10 mM pentoxifylline significantly decreased the time required for individual cells to be aspirated into a 4 microns pipet under constant pressure by 16 +/- 5%, 21 +/- 7%, and 41 +/- 8%, respectively (mean +/- SEM, p less than or equal to 0.05), compared with control. These experiments are the first direct demonstration of increased deformability in neutrophils treated with pentoxifylline. The results are consistent with the hypothesis that the beneficial effect of pentoxifylline on microvascular perfusion is partly due to an inhibition of PMN stiffness and activation.

Adult↗
PubMed1989

Rapid deformation of "passive" polymorphonuclear leukocytes: the effects of pentoxifylline.

Entry times for spherical (no pseudopods) polymorphonuclear leukocytes (PMNs) into a 4 microns micropipet have been measured as a function of pipet suction pressure (2,500-20,000 dyn/cm2) and concentration of the drug pentoxifylline (PTX, 0.1-10.0 mM). For control cells (0 mM PTX), entry rates (reciprocal entry times) increased almost linearly with increasing suction pressure, indicating a Newtonian-like behavior. With incubation in PTX solutions, entry rate vs. suction pressure became increasingly non-linear, suggesting a shear-thinning effect for the dissipative structure. At a given suction pressure the rate of entry showed a dose-dependent increase with increasing PTX concentration, the effect being most pronounced at high suction pressures (20,000 dyn/cm2). Also, with increasing PTX concentration two other effects were observed: i) there was a decreased incidence of cells that displayed pseudopodia, and ii) there was an increased incidence of cells forming hernias and an increased streaming of cell cytoplasm during aspiration. The first observation points to a down-regulation of the cell's functional ability to "activate" in response to surface/chemical stimuli, and the second indicates that both the cortical and cytoskeletal networks are weakened either by disruption and/or reduction in density of the protein polymers. These observations are in line with other recently published experiments which suggest that the rheological effects of pentoxifylline on PMNs may be associated with the state of actin.

Actins↗
PubMed1988

Psychophysiological reactivity to mental arithmetic stress in black and white normotensive men.

Racial differences in physiological responses to a behavioral stressor were examined. Thirty-four Black and 42 White male normotensives 34 to 55 years old (mean age = 43.01 years) performed a mental arithmetic task while blood pressure, heart rate, and skin conductance were recorded. Compared to Whites, Blacks had significantly higher baseline diastolic blood pressure (77.93 mm Hg vs. 73.11 mm Hg) and lower skin conductance levels (11.08 microS vs. 12.25 microS). These effects persisted during performance of the mental arithmetic task. However, when baseline differences were covaried, there were no significant physiological effects associated with the task. Analysis of changes in response levels from baseline revealed a nonsignificant trend for Whites to show greater increases in systolic blood pressure than Blacks. There were no significant race or family history effects. Further, task performance did not influence the outcome. Failure to demonstrate greater cardiovascular reactivity in Blacks and all men with a positive family history of hypertension is discussed with regard to possible "survivor effects" and methodologic limitations.

Adult↗