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Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 145 records · Page 8Linked to original sources
PubMed1996

Community-based respiratory viral infections in HIV positive patients with lower respiratory tract disease: a prospective bronchoscopic study.

OBJECTIVES: To evaluate the contribution of community-based respiratory virus infections to lower respiratory tract disease in HIV-1 infected individuals. DESIGN: Prospective clinical cohort study. SETTING: Specialist in-patient unit for HIV and AIDS, University College London Hospitals, London. SUBJECTS: 44 consecutive HIV-1 antibody positive patients who underwent 47 diagnostic bronchoscopies for evaluation of the symptoms and signs of lower respiratory tract disease. TIME: Winter months of 1994/95. MAIN OUTCOME MEASURES: Detection, in bronchoscopic alveolar lavage fluid, of infection with influenza A and B, respiratory syncytial virus (RSV), parainfluenza 1, 2 and 3 (by immunofluorescence and cell culture) and adenovirus and enteroviruses (by cell culture). RESULTS: No evidence of influenza, RSV, parainfluenza, adenovirus, or enterovirus infection was detected. CONCLUSIONS: Despite a marked increase in RSV and influenza B infection in the general population over the winter of 1994-95, respiratory virus infections were not detected in this cohort of HIV infected patients. As the organisms causing lower respiratory tract disease were related to immunosuppression, this study questions the value of routine identification of community-based respiratory viruses in this patient group.

AIDS-Related Opportunistic Infections↗
PubMed1996

Prevention and management of tuberculosis in HIV positive patients living in countries with a low prevalence of Mycobacterium tuberculosis.

We have re-examined the evidence on which current British Thoracic Society recommendations for primary and secondary prophylaxis and therapy of tuberculosis are based. We suggest that in a country such as the UK with a low prevalence of tuberculosis, primary prophylaxis should be offered primarily to tuberculin positive or anergic patients from high-incidence groups, including immigrants from high-prevalence countries, intravenous drug users and those with previous tuberculosis, that secondary prophylaxis be withheld from all but very high-risk patients and that four drug regimens which include ethambutol should be used for patients originating from, or who have lived in areas of the world with more than 2% primary isoniazid resistance.

Antitubercular Agents↗
PubMed1996

Computer simulations of voltage clamping retinal ganglion cells through whole-cell electrodes in the soma.

1. Computer simulations of voltage-clamp experiments in retinal ganglion cells were implemented to better understand the insights that can be obtained with this physiological approach. 2. Simulation studies of voltage clamping were based on the contemporary approach of using whole-cell recordings with low resistance electrodes attached to the soma. Realistic ganglion cell morphologies were provided by cell staining experiments in the mudpuppy retina; selected cells included small-, medium-, and large-field neurons whose morphologies were entered into a computer through a neuron tracing program. 3. Values for the specific membrane resistance (Rm) varied from 5,000 to 100,000 omega/cm2 to conform to the range of Rm values obtained with intracellular sharp electrodes and whole-cell recordings. 4. Synaptic input currents were simulated by injecting current with and without an underlying conductance change into different regions of the dendritic tree. The time-variant waveform of the current included a combined transient and sustained component similar to the waveform of ON-bipolar activation. 5. Simulations were base on 1) intact structures, which included the soma and the entire dendritic tree, and 2) a more limited cell geometry that included representation of the soma, but only part of the dendritic tree, to represent the restricted morphology that might be rendered after cutting the retina into 150-microns cross sections for retinal slice experiments. 6. The results of this study indicate that voltage clamping from the soma, with optimal, low resistance electrodes and series resistance compensation, provides an error-free voltage clamp for slow signals that are generated within a small electrotonic distance from the soma (approximately 0.1 lambda). 7. The ideal voltage-clamp conditions are optimized when synaptic conductances are small and nonlinear membrane elements are minimally activated: small-field neurons best approximate these conditions, but clamping errors are evident in these cells when more distal branches are activated. The degree of error in voltage clamping was much greater when medium-and large-field neurons were evaluated. 8. It was not possible to clamp action potentials (nonpropagating) even when they were generated near the soma in any of the three model cells examined. 9. Experimental paradigms were developed to demonstrate that inadequate voltage clamping can lead to errors in the interpretation of experimental data when relevant variables are not taken into consideration. Suggestions are made for determining and optimizing favorable clamp conditions.

Action Potentials↗
PubMed1996

Pseudomonas aeruginosa bronchopulmonary infection in patients with advanced human immunodeficiency virus disease.

Pseudomonas aeruginosa is increasingly reported as a respiratory pathogen in patients with advanced human immunodeficiency virus (HIV) disease. We retrospectively reviewed the chest radiographic appearances of 29 HIV-infected adults with bronchopulmonary infection in whom Pseudomonas aeruginosa was the sole respiratory pathogen isolated. The commonest radiographic abnormality was a diffuse reticular (11 patients) or reticulonodular (9 patients) infiltrate in the pulmonary interstitium. Alveolar opacification was seen in seven patients. Cavitation was rare (2 patients), as was ground-glass opacification (2 patients). Five patients had pleural effusions. No patient had mediastinal or hilar lymphadenopathy. Normal chest radiographs were seen in eight patients. Although the radiographic appearances of Pseudomonas bronchopulmonary infection in HIV-infected patients are non-specific, an interstitial infiltrate is a common finding. Pseudomonas aeruginosa should be considered along with the commoner pathogen Pneumocystis carinii in the differential diagnosis of an interstitial infiltrate in this group of patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

CT appearances of intrathoracic Kaposi's sarcoma in patients with AIDS.

Although there have been many studies of the plain radiographic appearances of intrathoracic Kaposi's sarcoma in patients with the acquired immunodeficiency syndrome, the computed tomography (CT) findings are less well established. We performed a retrospective review of the thoracic CT findings of 15 patients with tracheobronchial Kaposi's sarcoma diagnosed at bronchoscopy in whom concurrent respiratory infection had been excluded. The commonest CT finding was the presence of ill-defined nodules, seen in all patients. In eight patients more than 20 nodules were seen. Small areas of ground-glass attenuation surrounded one or more nodules in 11 patients. Bilateral perihilar infiltrates were seen in 14 patients, extending into the pulmonary parenchyma along bronchovascular bundles. Interlobular septal thickening was seen in 13 patients and fissural nodularity in 15 patients. To our knowledge this latter finding has not been described before. Discrete areas of ground-glass attenuation were seen in six patients. Small bilateral pleural effusions occurred in six patients; four patients had a pericardial effusion. Shotty mediastinal lymphadenopathy occurred in six patients, and mediastinal nodes greater than 1 cm were present in four patients. None of the patients had CT evidence of chest wall or bone involvement. Although none of these findings are specific, the combination of poorly defined nodules, fissural nodularity and a bronchovascular distribution of perihilar opacities on CT is highly suggestive of pulmonary Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Blood-Brain Barrier Integrity in HIV Infection:Evaluation by Contrast-Enhanced Magnetic Resonance Imaging.

This study assesses the integrity of the blood-brain barrier (BBB) in human immunodeficiency virus (HIV) seropositive individuals to magnetic resonance imaging (MRI) contrast agent Gd-DTPA. Twelve HIV seropositive patients and six control subjects had T2-weighted and serial pre- and post-contrast TI-weighted MRI. Ten of the twelve seropositive patients demonstrated white matter hyperintensity with or without atrophy on T2-weighted MRI and 8/10 who underwent neurological examination demonstrated neurological abnormalities. No statistically significant differences of trends in white matter pixel values were observed between pre- and post-contrast scans in any of the patients or controls. Serial T1-weighted MRI does not demonstrate any change in the integrity of the BBB to Gd-DTPA in HIV seropositive patients, regardless of the presence or absence of white matter hyperintensity with or without atrophy on T2-weighted MRI or clinical signs of HIV-I associated with cognitive/motor complex.

Blood-Brain Barrier↗
PubMed1996

Gallium-67 imaging of pericardial lymphoma in AIDS.

A 33-yr-old homosexual man with acquired immune deficiency syndrome (AIDS) and Mycobacterium avium intracellulare (MAI) infection presented with fever, sweats, lethargy and dyspnea. A chest radiograph showed cardiomegaly and an echocardiograph revealed a large pericardial effusion. After pericardial aspiration, which confirmed T cell non-Hodgkin's lymphoma, he remained dyspneic. Gallium-67 imaging was performed to determine whether the patient's residual dyspnea was related to pulmonary MAI infection or lymphomatous infiltration of the heart. Planar 67Ga scintigraphy revealed intense tracer uptake in two areas within the mediastinum and surrounding the entire heart shadow but no evidence of pulmonary MAI infection. SPECT 67Ga scintigraphy precisely localized the two mediastinal abnormalities and demonstrated the tracer uptake around the heart to be pericardial rather than myocardial. Gallium-67 scintigraphy suggested that pericardial lymphoma was the likely basis of the patient's dyspnea.

AIDS-Related Opportunistic Infections↗
PubMed1995

NBQX, an improved non-NMDA antagonist studied in retinal ganglion cells.

The quinoxaline derivative, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline (NBQX), significantly reduced the currents evoked by exogenous application of quisqualate (QQ), kainate (KA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) when applied to ganglion cells, using whole-cell recording in a slice preparation of the tiger salamander retina. A comparison between NBQX and CNQX indicates that NBQX is more effective in blocking AMPA receptors. Also, at up to 10 microM, NBQX has no effect on NMDA-induced currents. Thus at this concentration, NBQX shows no affinity for the glycine binding site of NMDA receptors. For this reason, NBQX is preferred over CNQX for a more effective and selective antagonism toward non-NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Morphology of ganglion cells in the neotenous tiger salamander retina.

The morphology of retinal ganglion cells in the neotenous tiger salamander (Ambystoma tigrinum) was analyzed with the aid of morphometric techniques to determine the diversity of cell types and to evaluate the widely held notion that this form of Ambystoma has a simple retina, with little variance among its cell morphologies. Single-cell staining was achieved through retrograde labeling with horseradish peroxidase injected around the optic nerve sheath followed by a period of several days before tissue processing; 83 well-labelled cells with axons were studied in detail with light microscopy and a computer-aided reconstruction system. Five different morphological cell classes were devised based on broad morphometric criteria such as the dendritic area of influence; the number, length, and complexity of dendritic branches; and the amount of overlap between neighboring dendrites. These classes included small simple, small complex, medium simple, medium complex, and large cells. In addition, a class of cells with numerous varicosities among the dendrites was separately analyzed. These swellings did not stain for catecholamines. Based on optical determinations of the dendritic sublamination pattern within the inner plexiform layer, presumed On-Off cells are present in all subclasses, whereas On cells predominate in the smaller cell groups. Presumed Off cells are well represented in the large field units, although the small total number of cells in this latter class leads to uncertainty regarding the significance of this observation. The diversity of ganglion cell morphology revealed in the present study argues against the assumption that the neotenous tiger salamander has a simple retina, with a relatively invariant set of ganglion cells. On the contrary, it appears that this aquatic form shows morphological diversity in the retinal ganglion cell population rivaling that reported for other vertebrates, including mammals. A functional role for the different cell classes is briefly considered.

Animals↗
PubMed1995

Quinoxalines block the mechanism of directional selectivity in ganglion cells of the rabbit retina.

Direction selectivity is a receptive field property displayed by neurons throughout the visual system. Previous experiments have concentrated on the role of lateral connections that use gamma-aminobutyric acid and acetylcholine. We have examined the role of excitatory amino acid receptors on direction-selective ganglion cell function in the rabbit retina. Application of the quinoxalines, a group of kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonists, selectively blocked the directional-selectivity mechanism, leaving cells responsive to both directions of movement. In contrast, direction selectivity was unaffected by N-methyl-D-aspartate receptor antagonists or L-2-amino-4-phosphonobutyric acid. Large reductions in acetylcholine release by starburst amacrine cells appear to parallel losses of direction selectivity observed in the quinoxalines. These results shed additional insights into the mechanism of direction selectivity.

Aminobutyrates↗
PubMed1995

Calcium waves in dissociated retinal glial (Müller) cells are evoked by release of calcium from intracellular stores.

Calcium imaging techniques were used to study intracellular free calcium ion regulation in isolated Müller cells in response to changes in extracellular potassium concentration and to caffeine and ryanodine. Müller cells were dissociated from the adult tiger salamander (Ambystoma tigrinum) retina and studied using the calcium indicator Fura-2 and video imaging microscopy techniques. Our results demonstrate that elevation of extracellular potassium in the presence of extracellular calcium evokes an increase in intracellular calcium ([Ca2+]i) throughout the length of the Müller cell. In contrast, in the absence of extracellular calcium, elevation of extracellular potassium can trigger a long latency, wave-like increase in [Ca2+]i that begins in the apical region of the Müller cell and moves toward the endfoot. A similar calcium wave can be evoked in Müller cells when they are exposed to caffeine or ryanodine, agents that cause release of calcium from intracellular stores in many cell types. These data suggest that [Ca2+]i may be altered in Müller cells through an extracellular pathway as well as through a ryanodine-sensitive intracellular release mechanism. The functional consequences of these changes in [Ca2+]i remain to be elucidated.

Animals↗
PubMed1995

Actions of phenylglycine derivatives at L-AP4 receptors in retinal ON bipolar cells.

Phenylglycine derivatives can act as agonists or antagonists at different metabotropic glutamate receptor (mGluR) subtypes, including subtypes sensitive to L-2-amino-4-phosphonobutyric acid (L-AP4). We examined the pharmacology of four phenylglycines at L-AP4 receptors in ON bipolar cells of the amphibian retina in situ. As previously shown for S-4-carboxy-3-hydroxyphenylglycine (S-4C3H-PG) (Thoreson W. B. and Miller R. F., J. Gen. Physiol. 103, 1019-1034, 1994), whole cell recordings indicate that S-3-carboxy-4-hydroxyphenylglycine (S-3C4H-PG) and S-4-carboxyphenylglycine (S-4C-PG) are L-AP4 receptor agonists in retina. Concentration-response curves for these compounds were obtained using the b-wave of the electroretinogram (ERG) as an assay for ON bipolar cell activity. The rank-order potency and IC50 values obtained were: S-4C-PG (204 microM) > S-4C3H-PG (399 microM) > or = S-3C4H-PG (558 microM). At 1 mM, RS-alpha-methyl-4-carboxyphenylglycine (RS-M4C-PG) suppressed the b-wave by less than 20%. This weak effect is attributed to agonist actions of RS-M4C-PG. The agonist actions of phenylglycines in retina are different from their effects at L-AP4 receptors in spinal cord or the expressed L-AP4-sensitive receptor subtype, mGluR4 (Kemp et al., Eur. J. Pharmac. Molec. Pharmac., 266, 187-192, 1994; Thomsen et al., Eur. J. Pharmac. Molec. Pharmac., 267, 77-84, 1994; Hayashi et al., J. Neurosci., 14, 3370-3377, 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobutyrates↗
PubMed1995

Hyperosmotic activation of transmitter release from presynaptic terminals onto retinal ganglion cells.

A method for evoking neurotransmitter release without light stimulation has been developed and applied to a retinal slice preparation of the tiger salamander (Ambystoma Tigrum). This method utilizes a micropipette containing hyperosmotic levels of sucrose in Ringer, positioned within the inner plexiform layer (IPL) under visual control. Intermittent pressure (between 0.1 and 2 bars) applied to the pipette evoked release of neurotransmitters which were evaluated with whole-cell recording (WCR) technique applied to cells in the ganglion cell layer. Pharmacological studies were used to characterize the properties of the hyperosmotic sucrose-evoked response (HSER) and in some cases, we compared the HSER with synaptic currents evoked by light stimulation. The HSER typically consisted of both inhibitory and excitatory components with a reversal potential in between that for chloride (approximately -60 mV) and non-specific cation channels (approximately 0 mV). Relatively pure inhibition or excitation could be revealed through pharmacological techniques by blocking the inhibition with picrotoxin/strychnine or by blocking the glutamatergic neurotransmission with D-AP7 (D-2-amino-7-phosphonoheptanoate) and NBQX (2,3-dihydroxy-6-nitro-sulfamoyl -benzo (F) quinoxaline). A comparison of light-evoked responses (LER) and the HSER suggested that they activate the same pool of releasable neurotransmitter.

2-Amino-5-phosphonovalerate↗
PubMed1995

Patterns of Ga-67 citrate accumulation in human immunodeficiency virus positive patients with and without Mycobacterium avium intracellulare infection.

Infection with Mycobacterium avium intracellulaire (MAI) is an increasingly important problem in patients infected with Human Immunodeficiency Virus (HIV). The objective of this study was to identify whether specific patterns of accumulation of Ga-67 citrate occur in HIV antibody positive patients with disseminated MAI infection. A retrospective review of Ga-67 scinigraphy was performed in 18 HIV antibody positive patients with MAI and 20 HIV antibody positive patients without MAI (who acted as a control group). A wide range of abnormalities was seen in both groups of patients and no single abnormality was diagnostic of MAI. However MAI was likely (sensitivity 89%, specificity 70%) in the presence of two or more of the following; accumulation of Ga-67 in lymph nodes, paranasal sinuses or colon or reduced uptake in the bone marrow. No specific abnormality on Ga-67 scintigraphy in HIV antibody positive patients enables a diagnosis of MAI to be made. Subtle and non specific abnormalities of Ga-67 may be the only scintigraphic evidence of active Mycobacterium avium intracellulare infection.

AIDS-Related Opportunistic Infections↗
PubMed1995

Cryptococcal pneumonia in patients with the acquired immunodeficiency syndrome.

Infection with Cryptococcus neoformans occurs with increased frequency in patients with the human immunodeficiency virus (HIV). Despite the lungs being the portal of entry for the fungus the commonest presentation is with meningitis: Cryptococcal broncho pulmonary infection occurs less commonly. The chest radiographs of fourteen HIV positive patients with cryptococcal pneumonia were reviewed. The commonest radiographic abnormalities were interstitial infiltrates, (nine patients) and focal or widespread alveolar consolidation (seven patients). Ground glass shadowing, not previously described in cryptococcal pneumonia, occurred in six radiographs, miliary nodules in one, lymphadenopathy in four, and small pleural effusions in three. Two patients had a normal chest radiograph. In contrast to previous reports, we found alveolar consolidation and ground glass shadowing to be common and nodules and cavitation to be rare. Cryptococcal pneumonia should be considered in the differential diagnosis of Pneumocystis carinii pneumonia, bacterial pneumonia and miliary tuberculosis in HIV positive patients.

AIDS-Related Opportunistic Infections↗