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Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 181 records · Page 10Linked to original sources
PubMed1995

The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance.

Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney. Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid. At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung.

Animals↗
PubMed1995

Radionuclide brain imaging in acquired immunodeficiency syndrome (AIDS).

Infection with the human immunodeficiency virus-type 1 (HIV-1) may produce a variety of central nervous system (CNS) symptoms and signs. CNS involvement in patients with the acquired immunodeficiency syndrome (AIDS) includes AIDS dementia complex or HIV-1 associated cognitive/motor complex (widely known as HIV encephalopathy), progressive multifocal leucoencephalopathy (PML), opportunistic infections such as Toxoplasma gondii, TB, Cryptococcus and infiltration by non-Hodgkin's B cell lymphoma. High resolution structural imaging investigations, either X-ray Computed Tomography (CT scan) or Magnetic Resonance Imaging (MRI) have contributed to the understanding and definition of cerebral damage caused by HIV encephalopathy. Atrophy and mainly high signal scattered white matter abnormalities are commonly seen with MRI. PML produces focal white matter high signal abnormalities due to multiple foci of demyelination. However, using structural imaging techniques there are no reliable parameters to distinguish focal lesions due to opportunistic infection (Toxoplasma gondii abscess) from neoplasm (lymphoma infiltration). In this manuscript we review the use of radionuclide brain imaging techniques in the investigation of HIV infected patients. Brain perfusion single photon emission tomography (SPET), neuroreceptor and positron emission tomography (PET) studies are reviewed. Greater emphasis is put on the potential of some radiopharmaceuticals, considered to be brain tumor markers, to distinguish intracerebral lymphoma infiltration from Toxoplasma infection. SPET with 201Tl using quantification (tumour to nontumour radioactivity ratios) appears a very promising technique to identify intracerebral lymphoma.

AIDS Dementia Complex↗
PubMed1994

NBQX suppresses inhibitory glycine currents in retinal ganglion cells.

The quinoxaline NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline) is a potent non-NMDA receptor antagonist, which appears to be relatively free of antagonistic action at the glycine binding site of the NMDA receptor. However, we report here that at 50 microM, NBQX significantly attenuated the inhibitory currents induced by the exogenous application of 100 microM glycine as observed using whole-cell recordings from ganglion cells in a slice preparation of the tiger salamander retina. In contrast, NBQX had no effect on GABA-mediated inhibition. This observation suggests that care should be taken when attributing the action of NBQX solely to its antagonism of non-NMDA glutamate receptors, particularly when higher concentrations are used.

Ambystoma↗
PubMed1994

Choreoathetosis/ballismus associated with pentamidine-induced hypoglycemia in a patient with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the association between acute choreoathetosis/ballismus and hypoglycemia related to pentamidine therapy in a patient with the acquired immunodeficiency syndrome. DESIGN: A single case report. MEASURES: Clinical observation, laboratory analysis of blood and cerebrospinal fluid, and magnetic resonance imaging of brain. RESULTS: No association was found apart from hypoglycemia. The abnormal movements and hypoglycemia did not recur following cessation of pentamidine. CONCLUSIONS: Hypoglycemia related to pentamidine therapy can cause neurologic disorders in patients with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Phaeochromocytoma presenting as acute hyperamylasaemia and multiple organ failure.

Phaeochromocytoma may present in many different ways. We report an unusual presentation of phaeochromocytoma in a man with hyperamylasaemia and multiple organ failure thought to be due to acute relapsing pancreatitis. Abdominal ultrasound and computerised tomography (CT) examinations revealed a mass at the tail of the pancreas. Fine needle biopsy of the mass precipitated headache, intense vasoconstriction and labile blood pressure. He proceeded to laparotomy, at which an 8 x 9 cm mass was found to be replacing the left adrenal gland. Histological examination revealed a phaeochromocytoma. This case illustrates that hyperamylasaemia and multiple organ failure may be unusual presentations of phaeochromocytoma and may be unusual presentations of phaeochromocytoma and phaeochromocytoma should be considered in the differential diagnosis of a peripancreatic mass found by ultrasound or CT.

Acute Disease↗
PubMed1994

An epidemiologic study of carpal tunnel syndrome and hand-arm vibration syndrome in relation to vibration exposure.

No Minnesota workers' compensation claims have been filed for permanent partial disability benefits with a diagnosis of hand-arm vibration syndrome (HAVS). A cross-sectional study was undertaken to evaluate 519 compensation claimants following carpal tunnel surgery. Workers with significant vibration exposure and symptoms compatible with HAVS were identified within the group. The results show that some workers are not diagnosed as having HAVS even though they meet the diagnostic criteria. This suggests that HAVS should be considered in the differential diagnosis when a worker presents with neural and/or vascular symptoms of the hands and fingers.

Adolescent↗
PubMed1994

Actions of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in retinal ON bipolar cells indicate that it is an agonist at L-AP4 receptors.

Metabotropic glutamate receptors (mGluRs) include receptors sensitive to L-2-amino-4-phosphonobutyrate (L-AP4) and 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). To determine whether 1S,3R-ACPD is an agonist at retinal L-AP4 receptors, whole cell voltage clamp recordings were obtained from mudpuppy ON bipolar cells in a superfused retinal slice and L-AP4 and 1S,3R-ACPD were bath applied. Both compounds evoked similar outward currents which reversed near 0 mV and were accompanied by an increased input resistance. Responses to both agonists washed out in parallel suggesting they act through the same second messenger pathway(s). Inhibitors of cGMP-PDE activity suppressed responses to both L-AP4 and 1SR,3RS-ACPD, suggesting that both compounds activate cGMP-PDE. Responses to 1S,3R-ACPD were occluded by prior activation of L-AP4 receptors, but not blocked by the non-AP4, mGluR antagonists, L-aminophosphonopropionic acid (L-AP3) or 4-carboxy-3-hydroxyphenylglycine (4C3H-PG). These results indicate that 1S,3R-ACPD is an agonist at L-AP4 receptors. 1S,3S-ACPD and 4C3H-PG evoked outward currents similar to L-AP4 suggesting they may also be L-AP4 receptor agonists. Using the b-wave of the ERG as an assay for ON bipolar cell responses, concentration/response curves were obtained for ACPD enantiomers. The rank-order potency of ACPD enantiomers at L-AP4 receptors in ON bipolar cells is similar to their rank-order potency at non-AP4, mGluRs in brain which suggests that the receptors possess similar binding sites and may be members of a common receptor family.

Aminobutyrates↗
PubMed1994

Genetic diversity in human-derived Pneumocystis carinii isolates from four geographical locations shown by analysis of mitochondrial rRNA gene sequences.

The opportunistic fungal pathogen Pneumocystis carinii is a frequent cause of pneumonia in immunocompromised hosts. In this study, we have compared the DNA sequences of a portion of the mitochondrial large-subunit rRNA gene of P. carinii (an informative locus showing up to 27% differences among isolates of P. carinii from human-, rat-, mouse-, ferret-, rabbit-, and horse-infected lungs) obtained from human-derived isolates from widely disparate geographical areas, including Britain, the United States, Brazil, and Zimbabwe. A single-base polymorphism which varied among samples was identified. Apart from this nucleotide, the DNA sequences of all samples were identical. The sequences of the British samples were shown to be stable over a period of 4 years. These data suggest that there is relatively low genetic diversity among isolates of human-derived P. carinii from different global regions.

Base Sequence↗
PubMed1994

Granulomatous Pneumocystis carinii pneumonia: DNA amplification studies on bronchoscopic alveolar lavage samples.

Three HIV positive subjects presented with symptoms and radiographic changes suggestive of Pneumocystis carinii pneumonia. Methenamine silver staining of bronchoscopic alveolar lavage (BAL) fluid was negative (from one sample in one patient and two samples in the other two patients). Open lung biopsy was performed because of uncertain clinical progress and diagnosis; all three patients were found to have multiple pulmonary granulomata encasing numerous P carinii organisms. DNA amplification, using P carinii specific oligonucleotides, was performed on stored bronchoscopic BAL samples. P carinii specific amplification product was detected by ethidium bromide staining after electrophoretic separation on agarose gel in one case, and by the more sensitive technique of oligohybridisation in all three cases. In granulomatous P carinii pneumonia organisms are rarely identified in bronchoscopic alveolar lavage samples using histochemical staining, but are detectable by DNA amplification, although not at levels which can be readily distinguished from low, subclinical infection.

Adult↗
PubMed1994

Feigned HIV infection/AIDS: malingering and Munchausen's syndrome.

Feigned HIV infection or acquired immunodeficiency syndrome (AIDS), in which people mimic infection with or disease due to HIV, accounted for 1.7% of admissions to our specialist HIV unit in Central London over a 5 year period. Of 12 patients with feigned HIV/AIDS, 11 were HIV antibody-negative, and one refused testing. Presenting histories were sometimes grandiose, unusually tragic, or unlikely in relation to the patients' healthy appearance, and often included admissions to other specialist HIV units. Substance abuse was suspected in over half of the patients described, a higher frequency than that observed in our HIV-infected patient population. The possibility of feigned HIV/AIDS should be remembered in persons with self-reported HIV infection. Recognition of this condition is important to avoid costly and potentially dangerous investigation and therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Community acquired lobar pneumonia in patients with HIV infection and AIDS.

BACKGROUND: Community acquired bacterial pneumonia is increasingly encountered in HIV infected individuals and some patients have a radiographic lobar pneumonia. METHODS: A retrospective review of clinical features, microbiological diagnosis, and outcome of community acquired lobar pneumonia was carried out in HIV positive patients admitted to a specialist unit from 1987 to 1993. RESULTS: Forty nine episodes occurred in 45 patients, all of whom were men. CD4 counts ranged widely. A bacteriological diagnosis was made in 25 episodes (51%), seven patients had more than one infective cause. The commonest pathogens were Streptococcus pneumoniae (11 episodes), Staphylococcus aureus (six), Pneumocystis carinii (three), Haemophilus influenzae (three), and Pseudomonas aeruginosa (two). Four patients died. Other complications included intrapulmonary cavitation or abscess formation (11 episodes), empyema (three), and pleural effusion (10 episodes). CONCLUSIONS: Many different infections cause community acquired lobar pneumonia in HIV positive men. Some patients have co-infections and there is a high complication rate.

Acquired Immunodeficiency Syndrome↗