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R F Miller

Publications and source records attributed to R F Miller.

At least 235 records · Page 13Linked to original sources
PubMed1991

Characterization of retinal and hippocampal L-AP4 receptors using conformationally constrained AP4 analogues.

In the past, the absence of useful 2-amino-4-phosphonobutanoic acid (AP4) analogues has hampered the pharmacological study and comparison of different systems which are sensitive to L-AP4. Several conformationally constrained AP4 analogues have now been synthesized: (E)- and (Z)-1-amino-3-phosphonocyclopentanecarboxylic acid [(E)- and (Z)-cyclopentyl AP4], and (E)- and (Z)-1-amino-3-phosphonocyclohexanecarboxylic acid [(E)- and (Z)-cyclohexyl AP4], and the recently synthesized cyclopropyl analogues (E)- and (Z)-2-amino-2,3-methano-4-phosphonobutanoic acid [(E)- and (Z)-cyclopropyl AP4]. Therefore, we have examined and report here the pharmacology of two retinal and two hippocampal L-AP4 sensitive systems using these analogues. In addition, the pharmacology of two kainic acid/alpha-amino-3-hydroxy-5-methylisoxazole-4- propionic acid (KAIN/AMPA) pathways and one N-methyl-D-aspartate (NMDA) hippocampal pathway was examined. We found that the rank order potency of the L-AP4 sensitive systems were similar though not identical. The KAIN/AMPA and NMDA systems had a quite different rank order of potencies than the L-AP4 systems. These data suggest that the L-AP4 receptors in these different systems are structurally similar to each other and differ from both KAIN/AMPA and NMDA receptors.

Aminobutyrates↗
PubMed1991

DNA amplification on induced sputum samples for diagnosis of Pneumocystis carinii pneumonia.

DNA amplification and silver staining were used to identify Pneumocystis carinii in bronchoscopic lavage and induced sputum samples during 51 episodes of respiratory illness in 47 subjects with HIV infection. In 20 episodes, in which the clinical diagnosis was pneumocystis pneumonia (PCP), silver stain was positive in 14 lavage samples (70%) and 7 sputum samples (35%), whereas DNA amplification was positive in 19 lavage samples (95%) and 18 sputum samples (90%). DNA amplification was positive in only 1 of 31 patients without PCP (PCP developed in this patient within 10 weeks). DNA amplification on induced sputum offers a powerful technique for diagnosis of PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Rods and cones activate different excitatory amino acid receptors on the mudpuppy retinal horizontal cell.

We have studied rod and cone neurotransmission onto horizontal cells (HCs) of the mudpuppy retina by: (1) dual whole-cell recordings from synaptically connected pairs in a superfused retinal slice preparation, and (2) intracellular recordings from HCs in a superfused retina-eyecup preparation. In the presence of relatively weak concentrations of broad spectrum excitatory amino acid antagonists, HC recordings show that cone-mediated responses were significantly more attenuated than those mediated by rods. These observations suggest that the HC postsynaptic receptors for rods and cones are pharmacologically different. One advantage of having distinct rod- and cone-activated receptors on second-order neurons may be to preserve different rod and cone functions under varying levels of light stimulation and provide separate means of regulating rod and cone neurotransmission onto the second-order cells.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Emergency laparotomy in patients with AIDS.

The presentation, operative management and final diagnosis were reviewed in 28 patients with AIDS (27 men and one woman) who underwent emergency laparotomy. On clinical and radiological examination, six patients showed features of toxic megacolon, five patients had small bowel obstruction, six patients had localized peritonitis and three had perforated viscus with generalized peritonitis. The most common disease processes were acute colitis in seven patients (associated with cytomegalovirus (CMV) infection in six), intra-abdominal lymphoma in five patients, acute appendicitis in five patients (associated with CMV infection in two), and atypical mycobacterial (MAI) infection in four patients. Two perioperative deaths occurred; one in a patient with acute pancreatitis and a second with generalized peritonitis. Later deaths were due to progression of AIDS, and patient survival at 1 month, 3 months and 6 months was 89 per cent, 64 per cent and 48 per cent, respectively. Lower operative mortality than in previously reported series may be due to earlier intervention in CMV toxic megacolon. Surgery, however, conferred less benefit in patients with acute abdominal pain from MAI infection or lymphoma. With careful patient selection, emergency laparotomy may achieve worthwhile palliation in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The APE nebuliser--a new delivery system for the alveolar targeting of particulate technetium 99m diethylene triamine penta-acetic acid.

We report the validation of a new delivery system--aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 microns and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV1 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of 99mTc DTPA, which was collected in a 35 1 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of 99mTc-DTPA. In view of the excellent intrapulmonary deposition of 99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Age-dependent changes in visual acuity and retinal morphology in pigeons.

The visual acuities of 17 pigeons that ranged in age from 2 to 17 years were tested with high-contrast, square-wave gratings. A systematic decline in visual acuity was observed that was well described by a logarithmic function. Pupillary diameter also declined with age, which decreased retinal illumination, but increased depth of focus. A small amount of presbyopia also was observed. Both the decrease in retinal illumination and the presbyopia accounted for only a trivial proportion of the acuity loss. No relationship between corneal or lenticular density and age was observed. Ophthalmoscopic examination of the optic media revealed no abnormalities associated with age. Microscopic examination of the area dorsalis of the retina (the high-density region specialized for frontal vision) revealed age-related losses of up to 33% of photoreceptors and 23% of cells in the ganglion-cell layer. A study of the photoreceptor layer within area dorsalis indicated that single-cone densities were unaffected by aging whereas the double-cone densities, which are the predominant photoreceptor type in the area dorsalis, were reduced in number by about one third. Calculation of the Nyquist limit both for photoreceptors and ganglion cells suggested that the decreased retinal density together with the decreased retinal illumination and presbyopia could not account for all of the observed acuity loss.

Aging↗
PubMed1991

Sputum induction for the diagnosis of pulmonary disease in HIV positive patients.

We prospectively compared sputum induction with bronchoalveolar lavage (BAL) in HIV positive patients presenting with acute respiratory episodes and also assessed the effects of using an experienced respiratory physiotherapist on the diagnostic yield from induced sputum. One hundred and fifty-one consecutive patients underwent sputum induction, in 96 the procedure was supervised by nursing and medical staff with no specific expertise (group I); in 55 patients a physiotherapist supervised sputum induction (group 2). Nine patients refused BAL having undergone sputum induction. Of the remaining 142 patients sputum induction failed (no sample expectorated) in 28 patients (25 from group 1 and three from group 2), the sample was inadequate (the material expectorated was not from the lower respiratory tract) in 29, and was adequate in 85 patients. Pneumocystis carinii was diagnosed in 82 patients (51 from group 1 and 31 from group 2). The sensitivity of induced sputum for the diagnosis of P. carinii was 13% and of BAL was 77%. In the subgroup of patients with an adequate induced sputum sample, the sensitivity of induced sputum was 28% and of BAL was 73%. Of the remaining 60 patients, 27 had other diagnoses made by induced sputum and BAL (eight patients), BAL only (15 patients) and induced sputum only (four patients). Eleven patients had bronchitis and responded to oral antibiotics. In 22 patients induced sputum and BAL were negative; alternative diagnoses were established by lung biopsy or by culture of blood, urine or CSF. During sputum induction, 15 patients had nausea and vomiting, eight became dyspnoeic, three had intractable cough and one developed acute bronchoconstriction; 17 patients found the procedure unpleasant. Compared with BAL, induced sputum has a lower diagnostic yield for P. carinii and other pathogens. Use of experienced, dedicated personnel increases the number of successful attempts at sputum induction but does not increase the diagnostic yield. Fibreoptic bronchoscopy and bronchoalveolar lavage remain necessary for patients with negative results from induced sputum and those whose disease course is at variance with the diagnosis made by sputum induction.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Characterization of serine's inhibitory action on neurons in the mudpuppy retina.

Experiments were performed in the superfused retina-eyecup of mudpuppies using intracellular electrophysiological techniques to evaluate the effects of serine on amacrine and ganglion cells. Serine was found to have a dose-dependent inhibitory effect mediated by the opening of chloride channels. Serine appears to act on a glycine receptor based on the observations that: (1) serine's effect is blocked by strychnine but not by bicuculline or picrotoxin, (2) in the presence of saturating glycine concentrations serine had no effect on membrane voltage or conductance, and (3) cells inhibited by serine were always sensitive to glycine, but not always sensitive to GABA. High pressure liquid chromatography measurements disclose that there is a high concentration of extracellular serine in the retina. The data indicate that serine could act as an inhibitory neurotransmitter.

Animals↗
PubMed1991

Continuous positive airway pressure ventilation for respiratory failure associated with Pneumocystis carinii pneumonia.

The value of continuous positive airway pressure (CPAP) ventilation via a tight fitting face mask was assessed in eight HIV-1 antibody-positive patients with Pneumocystis carinii pneumonia who were in hypoxaemic respiratory failure. All patients were conscious, able to protect their airway and not hypercapnic. Treatment was effective in seven patients. Prior to CPAP, mean (range) arterial oxygen tension was 6.7 (4.7-10.5) kPa in seven patients breathing oxygen via a face mask (FiO2 = 0.6), 6.1 kPa in one patient breathing room air and rose to 9.9 (6.8-12.8) kPa with CPAP (FiO2 = 0.6 and PEEP = 1.3 kPa in six patients and 2.6 kPa in one patient); the mean increase in PaO2 was 3.1 kPa (P less than 0.02). These seven patients experienced a rapid reduction in dyspnoea and their respiratory rate fell from a mean of 40 breaths min-1 to 32 breaths min-1 (P less than 0.001). One patient deteriorated rapidly on CPAP and died: no other complications were seen with this technique. CPAP was continued for a mean of 4.5 days and the seven responders all survived the episode of P. carinii pneumonia. We conclude that mask CPAP provides an effective means of improving oxygenation in severely hypoxaemic patients with P. carinii pneumonia.

Adult↗
PubMed1991

Expression of HIV-1 in the cerebrospinal fluid detected by the polymerase chain reaction and its correlation with central nervous system disease.

The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag, pol, and env) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1-positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects.

Adult↗
PubMed1991

Combined 67Ga citrate and 99Tcm-human immunoglobulin imaging in human immunodeficiency virus-positive patients with fever of undetermined origin.

Patients infected with the human immunodeficiency virus (HIV) suffer from serious and life-threatening infections. These patients often present with pyrexia but without localizing signs. Despite its high sensitivity in identifying focal infection 67Ga citrate scintigraphy lacks specificity; lymphoma and solid tumours may also be imaged. This presents particular problems in HIV-positive patients with pyrexia where the differential diagnosis is often between infection and lymphoma. In an attempt to improve the specificity of radionuclide imaging in these patients a combination of 67Ga citrate and the new agent 99Tcm-labelled human immunoglobulin (99Tcm-HIG) was used in 25 patients who were sequentially imaged with the two agents. Fourteen patients had 29 sites of microbiologically confirmed infection; 67Ga citrate identified 27 sites and 99Tcm-HIG identified 16 sites. Seven of the nine sites visualized with 99Tcm-HIG, but positive with 67Ga citrate, were intrathoracic. Abnormal concentration of 67Ga citrate, not due to infection, occurred at eight sites; five lymphoma, one gout, one recent fracture and one patient with prominent bone marrow islands. 99Tcm-HIG showed increased concentration of tracer in only one of the patients with lymphoma. A combination of 67Ga citrate and 99Tcm-HIG imaging in HIV-positive patients with pyrexia of unknown origin enables a differentiation between infection and lymphoma to be made more readily. The poor sensitivity of 99Tcm-HIG in the chest will limit its sole use in this patient group.

Adult↗
PubMed1991

Sclerosing cholangitis rapidly following anti-HIV-1 seroconversion.

A 22 year old man developed sclerosing cholangitis within two months of documented HIV-1 seroconversion. Sclerosing cholangitis should be included in the differential diagnosis of causes of abdominal pain and raised alkaline phosphatase enzyme levels in HIV-1 antibody positive patients without established CDC stage IV disease.

AIDS Serodiagnosis↗