Biomedical subjects
R F Miller
Publications and source records attributed to R F Miller.
HIV encephalopathy presenting as hypomania.
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HIV-associated dilated cardiomyopathy.
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Arterial desaturation in HIV positive patients undergoing sputum induction.
Arterial oxygen saturation (SaO2) was monitored continuously during and immediately after sputum induction in 41 HIV positive patients with respiratory symptoms and in 20 symptomless medical and nursing staff, who acted as control subjects. Arterial oxygen desaturation (defined as SaO2 less than or equal to 92%) occurred during sputum induction and persisted for up to 20 minutes after the end of the procedure in 11 of the 20 patients with Pneumocystis carinii pneumonia and in nine of the 21 patients with other respiratory diagnoses. None of the control subjects showed oxygen desaturation. Neither the severity of chest radiographic abnormalities, the alveolar-arterial oxygen gradient (both measured before sputum induction), nor baseline SaO2 prospectively identified the patients who developed oxygen desaturation. Two patients, one with pneumocystis pneumonia, developed dyspnoea and had a fall in arterial oxygen saturation to 84% within 10 minutes of starting sputum induction. The procedure was abandoned in both patients and in two further patients, who developed severe nausea and reaching but no oxygen desaturation. Sputum induction in HIV positive patients with respiratory symptoms may induce a fall in SaO2 that persists after this procedure. This may be important if other procedures are performed soon after sputum induction.
Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease.
Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)
Detection of Pneumocystis carinii with DNA amplification.
Oligonucleotide primers and probes were used in the polymerase chain reaction to amplify Pneumocystis carinii specific DNA sequences from alveolar lavage samples from 47 diagnostic bronchoscopies. No P carinii DNA was found in lavage from 10 immunocompetent patients; only low levels were found in 3 of 13 samples from immunosuppressed individuals without P carinii pneumonia (PCP), and the highest levels, readily demonstrated by simple ethidium bromide staining, were found in all of 16 samples from immunosuppressed patients with PCP confirmed by means of standard silver staining and in 4 from patients with clinical PCP but negative silver staining. DNA amplification provides a highly sensitive and specific technique for the identification of P carinii that should be valuable in epidemiological studies on this parasitic infection and in diagnosis.
Modeling the repetitive firing of retinal ganglion cells.
A kinetic model for the repetitive firing of retinal ganglion cells was synthesized from voltage-clamp data and evaluated by comparison with whole cell recordings from ganglion cells in the intact tiger salamander retina. Five distinct channels were included in the model and were sufficient to describe the physiologically observed frequency/current relationship in response to various levels of cell depolarization.
Difficulties with sputum induction for diagnosis of Pneumocystis carinii pneumonia.
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Ganciclovir for lumbosacral polyradiculopathy in AIDS.
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Nuclear medicine and AIDS.
Over the last decade the acquired immunodeficiency syndrome (AIDS) has become one of the leading causes of morbidity and mortality both in Europe and the United States. The disease is due to infection by the human immunodeficiency virus (HIV), which results in progressive loss of cellular immunity; consequently, patients are susceptible to both typical infections with high-grade pathogens and also low-grade opportunistic organisms. In addition, different cancers such as Kaposi's sarcoma and non-Hodgkin's lymphoma occur with increased frequency. Nuclear medicine has a central role to play in the diagnosis of these malignant and infectious conditions. This article reviews the role of radionuclide studies in the diagnosis of HIV-related disease.
Glucocorticoid therapy for severe Pneumocystis carinii pneumonia.
The majority of patients with AIDS and Pneumocystis carinii pneumonia respond to treatment with either high-dose cotrimoxazole or IV pentamidine. Glucocorticoids have been given as 'adjuvant' therapy in those patients who fail to respond to cotrimoxazole or pentamidine. This article discusses the role of glucocorticoids therapy in the treatment of severe Pneumocystis carinii pneumonia and reviews the evidence for their efficacy.
Amplification of mitochondrial ribosomal RNA sequences from Pneumocystis carinii DNA of rat and human origin.
Pneumocystis carinii specific DNA sequences have been cloned from the experimental rat model. The sequence of the gene coding for the large subunit of mitochondrial ribosomal RNA has been used to construct P. carinii specific oligonucleotide primers for the polymerase chain reaction. These oligonucleotides produced amplification of specific sequences from both P. carinii infected rat and human lung samplings, but none from a range of other organisms including potential pulmonary pathogens. Comparison of the sequence of amplified products from the infected rats and humans demonstrated limited but consistent differences between P. carinii from these two hosts and allowed for the construction of a human specific internal oligonucleotide. The application of the specific oligonucleotides for DNA amplification and subsequent Southern hybridisation affords extremely sensitive and specific detection of P. carinii in human samples, which may be applicable to both epidemiological research and clinical studies.
Cavitary lung disease caused by Mycobacterium avium-intracellulare in AIDS patients.
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Treatment of cytomegalovirus retinitis with zidovudine and ganciclovir in patients with AIDS: outcome and toxicity.
Sixteen patients with the Acquired Immunodeficiency Syndrome (AIDS) and cytomegalovirus retinitis were treated with ganciclovir alone (9 patients) or ganciclovir and zidovudine (6 patients). The duration of effective treatment, that is the number of weeks during which there was no deterioration in visual symptoms or retinal appearance, was comparable in both groups. However, six of the seven patients receiving concurrent therapy had to cease treatment temporarily because of bone marrow toxicity compared with one of the nine patients treated with ganciclovir alone. It is concluded that continuous concurrent therapy with oral zidovudine and intravenous ganciclovir is not possible unless unlimited supportive therapy including blood transfusion, is available.
AIDS and the lung. 5--Tests giving an aetiological diagnosis in pulmonary disease in patients infected with the human immunodeficiency virus.
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Granulomatous Pneumocystis carinii pneumonia in a patient with the acquired immunodeficiency syndrome.
A patient with an unusual granulomatous response to infection with Pneumocystis carinii is described. The diagnosis was made by open lung biopsy after two negative bronchoalveolar lavages.
Aids and the lung. 6-- Management of respiratory failure in patients with the acquired immune deficiency syndrome and Pneumocystis carinii pneumonia.
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N-methyl-D-aspartate receptors of ganglion cells in rabbit retina.
1. Intracellular and extracellular recordings were obtained from ganglion cells in the rabbit retina. The effect of N-methyl-DL-aspartate (NMDLA) and N-methyl-D-aspartate (NMDA) antagonists were studied with the use of a perfusion method for drug application. 2. NMDLA excited all ganglion cell types and caused a characteristic burst firing pattern, which is not typical of physiological responses in the retina. When synaptic transmission was blocked with cobalt, NMDLA still excited ganglion cells, indicating a direct action. 3. A comparison of DL-2-amino-5-phosphonopentanoate (DL-AP-5) and DL-2-amino-7-phosphonoheptanoate (DL-AP-7) revealed that DL-AP-7 was a more specific NMDA antagonist. DL-AP-5 partially blocked the b-wave of the electroretinogram (ERG), an action typical of L-2-amino-4-phosphonobutyrate (L-APB), which specifically blocks on channels in the retina. 4. DL-AP-7 reversibly blocked the action of NMDLA on all ganglion cell types, but the effects of kainate (KA) and carbachol were unchanged. AP-7 was stereospecific and pharmacologically specific, with action typical of a competitive NMDA antagonist in the rabbit retina. 5. DL-AP-7 did not block light responses driven by center or surround stimulation for ON or OFF ganglion cells. Directional selectively was unchanged by DL-AP-7. However, most ganglion cells showed a reduction, typically 20-30%, in the number of action potentials produced by light stimulation. 6. In contrast to a previous report, we found no evidence that DL-AP-7 specifically inhibited sustained ON ganglion cells. The inhibition of sustained ON responses by DL-AP-5, previously attributed to NMDA antagonism, is probably because of the weak APB activity of L-AP-5. 7. We conclude that NMDA receptors do not mediate the major light-driven input to ganglion cells in the rabbit retina. By exclusion, transmission from bipolar cells to ganglion cells appears to be carried mostly by KA or quisqualate (QQ) receptors. However, because NMDA antagonists reduced the number of action potentials produced by light stimulation, it is likely that NMDA receptors carry a portion of the signal transmission to ganglion cells. The presence of NMDA receptors on third-order neurons is consistent with the release of glutamate from presynaptic neurons such as bipolar cells.