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Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 217 records · Page 12Linked to original sources

Typing by DNA probe of mycobacterial species isolated from patients with AIDS.

Restriction fragment length polymorphism (RFLP) types of Mycobacterium avium intracellulare and Mycobacterium kansasii isolated from patients with AIDS were examined. We demonstrate that one RFLP type is much more common than others which confirms previous findings. Carriage of individual RFLP types is constant over long periods of time. In addition, we document a disseminated infection in a patient with M. avium intracellulare of three RFLP types.

AIDS-Related Opportunistic Infections↗

Fusobacterium nucleatum bacteraemia with multiple liver abscesses in an HIV-I antibody positive man with IgG2 deficiency.

Liver abscess formation due to Fusobacterium nucleatum is rare. We describe an HIV-I antibody positive man, with normal surrogate markers of cell-mediated immunity, who presented with F. nucleatum bacteraemia and liver abscess formation. He was found to have IgG2 subclass deficiency. This case illustrates the clinical importance of altered B-cell function in patients who are at an early stage of HIV disease.

Adult↗

Hepatobiliary scintigraphy in the diagnosis of AIDS-related sclerosing cholangitis.

Twenty human immunodeficiency virus (HIV)-positive patients were studied who presented with right upper quadrant abdominal pain, with or without abnormal biochemical liver function tests, in whom AIDS-related sclerosing cholangitis (ASC) was suspected. The results obtained from hepatobiliary scintigraphy using 99Tcm-IODIDA were compared with data from endoscopic retrograde cholangiopancreatography (ERCP), ultrasound and histological data from liver biopsy or post mortem. 99Tcm-IODIDA was abnormal in 14 patients. Liver biopsy, ERCP or post mortem confirmed ASC in 11 patients of whom 10 had an abnormal 99Tcm-IODIDA study. Ultrasound was performed in eight of the patients with confirmed ASC but was abnormal in only five of these. One patient with mild ASC on ERCP and Kaposi's sarcoma had a normal 99Tcm-IODIDA. In HIV-positive patients with right upper quadrant pain, imaging with 99Tcm-IODIDA provides a non-invasive screening test which may help to determine those patients who should be referred for ERCP.

Acquired Immunodeficiency Syndrome↗

Occult alveolar haemorrhage in bronchopulmonary Kaposi's sarcoma.

Evidence of occult alveolar haemorrhage was sought by Perls's staining of bronchoalveolar lavage fluid to detect haemosiderin laden macrophages in 63 human immunodeficiency virus positive (HIV-1) men who underwent bronchoscopy. Twenty three patients had bronchopulmonary Kaposi's sarcoma; occult alveolar haemorrhage was present in 16 of these (including two in whom no tracheobronchial lesions were evident at bronchoscopy, but in whom the diagnosis was confirmed at necropsy). Forty patients had other diagnoses including Pneumocystis carinii pneumonia and bacterial pneumonia; 18 had occult haemorrhage. Occult alveolar haemorrhage seems to be a non-specific finding in HIV-1 positive men undergoing bronchoscopy.

Adult↗

Bronchopulmonary Kaposi's sarcoma in patients with AIDS.

BACKGROUND: Kaposi's sarcoma in HIV antibody positive patients may affect the lungs. This study describes the presentation, chest radiographic appearances, and pulmonary function test abnormalities in patients with AIDS who had tracheobronchial Kaposi's sarcoma. METHODS AND RESULTS: Twenty nine (8%) of 361 consecutive HIV antibody positive patients undergoing bronchoscopy for respiratory symptoms had tracheobronchial Kaposi's sarcoma. Eight patients had intercurrent infections and one had previously received chemotherapy for cutaneous Kaposi's sarcoma; these patients were excluded. Seven of the remaining 20 patients had localised Kaposi's sarcoma (lesions confined to the trachea or the subsegments of one lobe) and 13 had widespread Kaposi's sarcoma (affecting the trachea and one lobe or the subsegments of more than one lobe); 19 patients also had cutaneous and palatal Kaposi's sarcoma. Seven patients, four with widespread disease, had a normal radiograph. All patients had reduced transfer factor (TLCO) and transfer coefficient (KCO) but only those with widespread disease had reductions in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). Follow up pulmonary function testing in seven patients (median three months later) showed further reductions in TLCO. All four patients who received no treatment had progressive radiographic abnormalities; bronchoscopy in two patients showed progressive tracheobronchial disease, and two patients had further reductions in FEV1 and FVC. In three patients treated with chemotherapy palliation of symptoms was achieved but two had further reductions in FEV1 and FVC and the radiograph deteriorated. Bronchoscopy showed regression of disease in only one patient. CONCLUSION: Pulmonary Kaposi's sarcoma produces abnormalities of TLCO even in patients with localised disease; airflow obstruction may occur in patients with widespread disease. Bronchoscopic reassessment of the extent of disease may not accurately reflect response to chemotherapy.

Acquired Immunodeficiency Syndrome↗

Site of action potential initiation in amphibian retinal ganglion cells.

1. We applied morphological, pharmacological, electrophysiological, and computer simulation techniques to analyze the origin of impulse initiation in amphibian retinal ganglion cells. 2. Morphological studies of retinal ganglion cells in the mudpuppy (Necturus maculosus) and larval tiger salamander (Ambystoma tigrinum) were carried out with the use of either retrograde or intracellular labeling with horseradish peroxidase. These studies identified a characteristic thinning of the axon that begins after the initial segment of axon emerges from the ganglion cell soma or primary dendrite. Morphometric analysis of the thin segment revealed an average length of 74 microns with a standard deviation of 22 microns. For 20 conventionally placed ganglion cells, the length of the thin segment could not be correlated with soma size, initial segment diameter, or distance from the optic disk. There was also little or no correlation for seven displaced ganglion cells. The diameter of the thin segment was below reliable estimation by light microscopy. 3. We studied the possible significance of the thin axonal segment for ganglion cell impulse generation through a combination of electrophysiological recordings (intracellular and whole-cell recordings) together with computer modeling experiments. 4. Electrophysiological experiments are consistent with the idea that the thin segment and cell soma are less excitable than the initial segment region, which appears to be the principal site of initiation of the nerve impulse. The initial segment is that portion of the axon that is bounded by the soma (or proximal dendrite) at its origin and the thin segment at its distal end. 5. Computer simulations of impulse activation were carried out with the use of two different anatomic constraints: one class of simulations did not take into account the thin segment and assumed uniform cylinder conditions, whereas the other class of simulations included a model of the thin axonal segment. These comparative simulations indicate that the thin segment must contain a relatively high density of voltage-gated Na+ channels and support impulse traffic to account for physiological observations on orthodromic and antidromic impulse propagation. In addition, to match the physiological recordings, it is necessary for both the initial segment and the soma compartments to contain moderately high levels of Na+ channels. 6. Our physiological and simulation studies are consistent with the idea that the nerve impulse is normally initiated in the initial segment of axon and then spreads to activate a somatic impulse in the retrograde direction and the axonal impulse in the anterograde direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Physiological and morphological correlations of horizontal cells in the mudpuppy retina.

1. Horizontal cells (HCs) of the mudpuppy (Necturus maculosus) retina were physiologically characterized with the use of intracellular recordings in a superfused, dark-adapted, retina-eyecup preparation. 2. Physiological analysis included an evaluation of rod versus cone input and a determination of the receptive field size with the use of a displaced slit of light. 3. The morphology of HCs was established through intracellular staining with horseradish peroxidase (HRP) and Lucifer yellow mixed in a single electrode. 4. Three types of horizontal cells were identified, each associated with a distinct morphology. Physiological subtypes included luminosity (L) and chromaticity (C) cells. Morphological diversities included single axon-bearing, multiple axon-bearing and, nonaxon-bearing cells. All C-type HCs lacked axons. 5. Approximately 90% of HCs encountered in this study were L-type cells, which received sign-conserving inputs from both rods and cones. These cell types contained one or more long axons that often stretched greater than 500 microns. This group was morphologically diverse, particularly with respect to variations in the number of axons, but we were unable to correlate this diversity with any unique set of physiological properties. 6. Several C-type HCs were identified (n = 8). These cells depolarized to a low-intensity, short-wavelength (SW) stimulus, whereas they hyperpolarized to high-intensity, long-wavelength stimuli. Morphologically, these cells were axonless (n = 4), with relatively small dendritic fields. 7. A third group of HCs were classified as "short wavelength preferring" HCs (n = 7). These cells responded better to a SW stimulus at all intensity levels. They were thus dissimilar to the common L-type HCs, which showed an apparent rod to cone transition as the stimulus intensity increased, suggestive of a shift from rod to cone preference. Morphologically, these cells were axonless (n = 2), but had broader dendritic fields than the C-type HCs. 8. Our observations indicate that the horizontal cell population of the mudpuppy retina is considerably more complex than previously supposed. The existence of both axon-bearing and axonless HCs, which could be correlated with L- and C-type physiology, implies that HCs may support more than one function in outer retina processing.

Animals↗

Pharmacological properties of N-methyl-D-aspartate receptors on ganglion cells of an amphibian retina.

1. The pharmacological characteristics of the N-methyl-D-aspartate (NMDA) receptors on amphibian retinal ganglion cells were studied to determine their similarities or differences from NMDA receptors found in mammalian central nervous system (CNS) cells. Cells were tested with a variety of NMDA antagonists acting at sites on the NMDA receptor/ion channel complex. 2. Whole-cell voltage-clamp recordings were obtained from ganglion cells of the larval tiger salamander with a retinal slice preparation. All cells responded with inward currents (Vhold = -70 mV) when exposed to bath applications of NMDA, kainate (KA), and glutamate (GLU). NMDA currents reversed near 0 mV and showed a negative slope conductance region in the presence of external Mg2+. 3. NMDA-evoked inward currents could be blocked by application of 300 microM D-2-amino-7-phosphonoheptanoate (DAP7), 100 microM Zn2+, 25 microM 7-chloro-kynurenate (7-cl-KYN), 1 microM MK-801, and 5 mM Mg2+. These results indicate that like mammalian NMDA receptors the amphibian NMDA receptor possesses binding sites for NMDA, glycine, zinc, dissociative anesthetics, and Mg2+. 4. NMDA responses were evoked in the presence of 1 mM extracellular Mg2+ in 100% of cells tested when held at -70 mV. Furthermore, there was a resting conductance at -70 mV and membrane current noise that could be attenuated by the application of NMDA-specific antagonists suggesting a tonic activation of NMDA receptors for cells at the resting potential.

2-Amino-5-phosphonovalerate↗

Effect of sulfidopeptide leukotriene receptor antagonists on endotoxin-induced pulmonary dysfunction in awake sheep.

We studied the effects of two structurally unrelated sulfidopeptide leukotriene receptor antagonists on endotoxin-induced pulmonary dysfunction in chronically instrumented unanesthetized sheep. The agents employed were L-660,711 (MK-571) (Merck-Frosst, Canada) and SK&F 104,353 (Smith Kline and French, King of Prussia, PA). The efficacy and specificity of the agents were verified in sheep by administering boluses of exogenous leukotrienes (LTB4, LTC4, LTD4, and LTE4) in doses as great as 100 micrograms while monitoring lung mechanics and vascular pressures. The antagonists blocked the changes in lung mechanics and pulmonary hemodynamics induced by the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) while having no effect on the animals' responses to LTB4. The endotoxin studies were performed by administering endotoxin alone (Escherichia coli endotoxin 0.75 microgram/kg) or endotoxin after pretreatment with one of the sulfidopeptide leukotriene receptor antagonists. In control studies, each animal received a continuous infusion of one of the receptor antagonists for a duration identical to that of the endotoxin studies. Neither L-660,711 nor SK&F 104,353 significantly altered the endotoxin-induced changes in pulmonary hemodynamics, lung mechanics, lung fluid and solute exchange, oxygenation, or leukopenia. Peak lung lymph thromboxane B2 levels were significantly lower in sheep pretreated with L-660,711. When the antagonists were given alone, no effects were seen. We conclude that (1) sulfidopeptide leukotrienes do not measurably contribute to endotoxin-induced pulmonary dysfunction in chronically instrumented sheep; (2) sulfidopeptide leukotrienes may contribute to thromboxane release after endotoxin.

Animals↗