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Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 19 recordsLinked to original sources
PubMed1997

Lobar or segmental consolidation on chest radiographs of patients with HIV infection.

PURPOSE: To correlate chest radiographic abnormalities with diagnoses in HIV infected patients presenting with acute respiratory symptoms and lobar or segmental consolidation. MATERIALS AND METHODS: Retrospective review of chest radiographs of 53 HIV infected patients with lobar or segmental consolidation, and their microbiological and cytological diagnoses. RESULTS: A specific diagnosis was made in 35 patients of which 12 had Pneumocystis carinii pneumonia (including four co-infections) and 23 had bacterial pneumonias (10 of these were due to Streptococcus pneumoniae and four to Mycobacterium tuberculosis). Microbiological and cytological tests were negative in 18 patients. Non-specific radiographic features included bronchial wall thickening (79%), reticulonodular or reticular change (55%), effusions (38%) and lymphadenopathy (25%); effusions favoured a bacterial aetiology. Ten of the 12 cases with P. carinii pneumonia had upper lobe consolidation (three of these had received inhaled pentamadine). Of 13 other cases of upper lobe consolidation, eight were due to pyogenic infection and only one to M. tuberculosis alone. CONCLUSION: A wide variety of causative agents may produce lobar or segmental consolidation in HIV infected individuals, and the most common cause is bacterial infection. Where there is upper lobe consolidation P. carinii pneumonia should be considered in the differential diagnosis.

AIDS-Related Opportunistic Infections↗
PubMed1997

Raised serum nitrate and nitrite levels in patients with multiple sclerosis.

Nitric oxide and its highly reactive derivative peroxynitrite have been implicated as non-specific inflammatory mediators of neuronal and oligodendrocyte damage and death in multiple sclerosis. In a cross-sectional study we found levels of the nitric oxide metabolites nitrate and nitrite to be raised in the serum of patients with demyelinating disease (65.6 microM (SD 32.9)), acquired immune deficiency syndrome (57.9 microM (SD 34.9)) and inflammatory neurological disease (57.5 microM (SD 31.3)), compared with normal control subjects (32.8 microM (SD 12.2)) and patients with non-inflammatory neurological disease (41.1 microM (SD 12.3), p < 0.001). Nitric oxide metabolites were raised in all clinical subtypes of multiple sclerosis, as well as in clinically isolated syndromes compatible with demyelination, and were not related to progressive disease or disability. This study provides further evidence for a role of nitric oxide in the immunopathogenesis of inflammatory diseases of the central nervous system, including multiple sclerosis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Two phenylglycine derivatives antagonize responses to L-AP4 in ON bipolar cells of the amphibian retina.

Light responses of retinal ON bipolar cells are mediated by metabotropic glutamate receptors selectively activated by L-2-amino-4-phosphonobutyric acid (L-AP4). Antagonists to L-AP4 receptors in ON bipolar cells have not previously been identified. This study examines the electrophysiological effects of (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), (RS)-4-4-chloro-3,5-dihydroxyphenylglycine (CDHPG) and (RS)-3,4,5-trihydroxyphenylglycine (THPG), at L-AP4 receptors in ON bipolar cells of the amphibian retina. Unlike its actions in spinal cord, in retinal ON bipolar cells MAP4 is a weak agonist which exhibits no detectable antagonism to L-AP4. On the other hand, CDHPG exhibits a mixture of agonist and antagonist properties. Addition of Co2+ and oxygenation of CDHPG turns the solution brown and enhances antagonist effects, suggesting that the antagonism reflects actions of a breakdown product of CDHPG. Although THPG did not prove to be this breakdown product, it also has electrophysiological effects consistent with an L-AP4 receptor antagonist. The results suggest that THPG and breakdown products of CDHPG may be antagonists to L-AP4 receptors in retinal ON bipolar cells, although the possibility that these compounds antagonize effects of L-AP4 by acting at some site in the transduction pathway of L-AP4 receptors cannot yet be excluded.

Aminobutyrates↗
PubMed1997

Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection.

OBJECTIVE: To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals. DESIGN: Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals. SETTING: Two specialists HIV/AIDS outpatient facilities in London. PARTICIPANTS: Eighty-four HIV-1 seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls. MAIN OUTCOME MEASURES: Single voxel, gradient-localized proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks. RESULTS: There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01). CONCLUSION: Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

Brain↗
PubMed1997

Comparison of magnetic resonance imaging with neuropathological findings in the diagnosis of HIV and CMV associated CNS disease in AIDS.

OBJECTIVES: To compare the results of clinical assessment and MRI with neuropathological findings in the diagnosis of HIV and cytomegalovirus (CMV) associated CNS disease. METHODS: A retrospective study of 35 patients infected with HIV who were examined at necropsy between four and 70 (median 20) days after neurological assessment and MRI. RESULTS: Of the 35 patients, 19 had diffuse white matter hyperintensity on T2 weighted MRI, six of whom also had focal lesions. Nine other patients had focal white matter lesions and seven had changes in cortical atrophy only. Necropsy in the 19 with diffuse white matter hyperintensity showed HIV leukoencephalopathy (HIVLEP) with encephalitis in 10, CMV encephalitis in three, both HIVLEP/HIV encephalitis and CMV encephalitis in one, lymphoma in three, and non-specific inflammation in two. Necropsy in the 16 other patients without diffuse white matter hyperintensity showed CMV encephalitis in six, HIV encephalitis (without HIVLEP) in two, CMV encephalitis and HIVLEP/HIV encephalitis in one, non-HIV associated abnormalities in five, herpes simplex encephalitis in one, and lymphoma in one. CMV DNA was detected in CSF of five of seven patients with CMV encephalitis and in two of two with CMV associated polyradiculopathy but without CMV encephalitis. Diffuse white matter hyperintensity on MRI had a sensitivity of 100%, a specificity of 66.6%, and a positive predictive value of 58% for diagnosis of HIVLEP. CONCLUSION: Diffuse white matter hyperintensity on MRI can be due to either HIV or CMV associated pathology or non-specific abnormalities.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Diagnostic utility of bone marrow sampling in HIV positive patients.

OBJECTIVE: To evaluate the diagnostic utility of bone marrow (BM) sampling in HIV positive patients. DESIGN: Retrospective cohort analysis. SETTING: Specialist HIV/AIDS service in London. SUBJECTS: 215 consecutive HIV infected patients undergoing 246 BM samplings for investigation of pyrexia without localising signs, haematological abnormalities, or staging/investigation of lymphoma. MAIN OUTCOME MEASURE: Diagnostic yield from (and impact on management of) BM sampling. RESULTS: Of 122 BM samples taken to investigate pyrexia, 33 (27%) revealed the cause on microscopy: unexpected lymphoma in seven (6%), mycobacteriosis in 25 (20%), and toxoplasmosis in one (1%). Marrow infiltration was confirmed in 11 of 38 BM samples taken for staging/investigation of lymphoma/leukaemia. In afebrile patients, of 22 with pancytopenia, BM samples showed HIV associated changes in 17 and specific diagnoses in five (mycobacterial infection in three, haemophagocytic syndrome in one, and megaloblastic change due to vitamin B-12 deficiency in one); of 21 with isolated thrombocytopenia, 20 (95%) BM samples showed immune thrombocytopenic purpura to be the cause and the remaining patient had BM changes of aplasia; of 29 with isolated anaemia, 28 had BM changes of HIV associated dysplasia/erythroid dysplasia and one had unsuspected iron deficiency; all 10 with isolated leucopenia/neutropenia had BM changes ascribed to HIV infection exacerbated by concurrent sepsis or medication; of four BM samples taken for other reasons, one showed mycobacterial infection. CONCLUSIONS: BM sampling has diagnostic utility in HIV infected patients with pyrexia without localising signs, pancytopenia, and staging/investigation of lymphoma; this test has little value in the investigation of afebrile patients with isolated thrombocytopenia, anaemia, or leucopenia as HIV is usually the underlying cause.

AIDS-Related Opportunistic Infections↗
PubMed1997

Reducing extracellular Cl- suppresses dihydropyridine-sensitive Ca2+ currents and synaptic transmission in amphibian photoreceptors.

A reduction in extracellular chloride suppresses light-evoked currents of second-order retinal neurons (bipolar and horizontal cells) by reducing release of glutamate from photoreceptors. The underlying mechanisms responsible for this action of reduced extracellular Cl- were studied with a combination of electrophysiological recordings from single neurons in a retinal slice preparation and image analyses of intracellular Ca2+ (Fura-2) and pH [2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester] in dissociated photoreceptors. The results show that reducing extracellular Cl- suppresses a dihydropyridine (DHP)-sensitive Ca2+ current (I(Ca)) in photoreceptors. It is proposed that suppression of I(Ca) results in suppression of photoreceptor neurotransmission. The suppressive effect of low Cl- on I(Ca) is not due to antagonism by the substituting anion nor is it mediated by changes in extracellular or intracellular pH. We conclude that normal extracellular levels of Cl- are important for maintenance of the voltage-gated Ca2+ channels that support neurotransmission from photoreceptors. Several ideas are presented about the mechanisms by which Cl- supports photoreceptor neurotransmission and the possibility that modulations of Cl- might play a physiological role in the regulation of Ca2+ channels in photoreceptors and, hence, photoreceptor function.

Ambystoma↗
PubMed1996

The mechanism by which NBQX enhances NMDA currents in retinal ganglion cells.

When the quinoxaline NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline), a KA/AMPA antagonist, is bath applied to the tiger salamander retina, a paradoxical action is evident in the light-evoked synaptic responses of ganglion cells: NBQX enhances excitatory synaptic currents at light onset observed under whole-cell voltage-clamp conditions in a perfused retinal slice preparation. This observation was surprising because synaptic inputs into ganglion cells that are mediated by KA/AMPA receptors are entirely blocked by NBQX. Thus, the NBQX-enhanced current is entirely mediated by NMDA receptors. The purpose of this study was to determine the mechanism(s) by which blocking KA/AMPA receptors appears to enhance NMDA currents. Using hyperosmotic sucrose stimulation to activate neurotransmitter release from the inner retina, we observed that NBQX augmented the sucrose-evoked response, suggesting that at least a component of this enhancement may reside in the inner retina. NBQX does not enhance NMDA currents activated by bath applied NMDA, demonstrating that the NBQX-induced enhancement does not result from modulation of NMDA receptors. Voltage-clamp studies, carried out at the appropriate holding potential, indicate that NBQX enhances glutamatergic transmission and reduces inhibitory inputs onto ganglion cells. In the presence of strychnine and picrotoxin, the NBQX-induced enhancement of NMDA currents is eliminated, suggesting that NBQX facilitates the expression of NMDA currents by a selective and partial reduction of inhibitory mechanisms. Additional studies suggest that part of the NMDA enhancement by NBQX is evident at the postsynaptic level, but a presynaptic component probably also participates, perhaps at the level of bipolar cell terminals. One way to account for this observation is to assume that a subpopulation of inhibitory amacrine cells requires KA/AMPA receptors exclusively for their synaptic activation: previous studies of sustained amacrine cells support this interpretation. Thus the NBQX-induced enhancement phenomenon may reflect a network-selective distribution of NMDA and KA/AMPA receptors among third-order neurons.

Animals↗
PubMed1996

Cerebral magnetic resonance relaxometry in HIV infection.

A prospective, cross-sectional study was designed to determine the magnetic resonance relaxation times of cerebral white matter in human immunodeficiency virus (HIV) infected individuals. T1 and T2 were estimated at 1.5 T using four-point methods. Seventy-five HIV-1 seropositive subjects, 48 seronegative blood donors, and 17 seronegative homosexual men were studied. Associations between relaxometry and clinical classification, neurological status, immunological status, and qualitative MRI were investigated. Statistically significant differences in white matter T1 relaxation time were found comparing low-risk control and AIDS groups (p < .005), seropositive subjects with neurological signs and those without (p < .005), and subjects with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x 10(6)/1) CD4 cell counts (p < .05). These findings add to the body of information that reveals no HIV-related change in the brain before the onset of symptomatic immunosuppression and go someway to validating the previous visually rated, qualitative findings. Statistically significant difference in white matter T2 relaxation time were also found comparing the two control groups (p < .005) highlighting the need for appropriate controls.

AIDS Dementia Complex↗
PubMed1996

The spectrum of MRI findings in CNS cryptococcosis in AIDS.

We retrospectively reviewed the cranial MRI appearances of 25 patients with AIDS and microbiologically proven central nervous system (CNS) cryptococcosis. Four patients had a normal scan. Ten patients had dilated perivascular Virchow-Robin spaces that were hyperintense on T2-weighted images. Nine of these patients developed progressive cryptococcomas, eight in the basal ganglia and one in the cerebral white matter. The cryptococcomas displayed high signal on T2-weighted and intermediate to low signal on T1-weighted images. None enhanced after dimeglumine gadopentetate. No abnormal dural or leptomeningeal enhancement was detected in any patient. One patient developed an acquired arachnoid cyst during treatment of CNS cryptococcosis which was thought to represent a focal collection of organisms and mucoid material within the subarachnoid space. In addition either cerebral atrophy and/or background white matter hyperintensity on T2-weighted images was present in 19/25 patients. In two patients the neuropathological findings at autopsy correlated well with the imaging abnormalities. In conclusion, this spectrum of MRI appearances in CNS cryptococcosis reflects the pathological mechanism of invasion by the fungus, but a normal scan or one with features of CNS HIV infection such as atrophy or white matter hyperintensity does not exclude the diagnosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Sub-cortical white-grey matter contrast on MRI as a quantitative marker of diffuse HIV-related parenchymal abnormality.

White matter change occurs in human immunodeficiency virus (HIV) encephalopathy, which may be difficult to assess subjectively especially in the early stages of disease. This study applies a quantitative approach to the assessment of this finding. Sixty-three HIV seropositive subjects, 47 seronegative blood donors and 17 seronegative homosexual men underwent axial T2 weighted MRI of the brain at 1.5T. Quantitative analysis was performed by obtaining the pixel contrast between parieto-occipital white matter and head of caudate grey matter (Cwg). Highest values of Cwg were found in a subgroup of subjects with AIDS who had diffuse/patchy white matter abnormalities and atrophy on qualitative image assessment. Statistically significant differences were found in Cwg between subjects with high (> or = 200 x 10(6)/I) and low (< 200 x 10(6)/I) CD4 lymphocyte counts (P < 0.05) and between subjects with and without HIV-1 associated cognitive/motor complex (P < 0.05). This technique provides an objective measure of diffuse HIV-related parenchymal abnormality seen on T2 weighted MRI.

AIDS Dementia Complex↗
PubMed1996

Detection of polyomaviral DNA in clinical samples from immunocompromised patients: correlation with clinical disease.

Clinical samples from immunocompromised patients were screened for polyomaviral sequences by nested polymerase chain reaction (PCR) to evaluate the association of these viral infections with progressive multifocal leukoencephalopathy (PML). JC virus (JCV) DNA was detected in 19 of 23 CSF samples and all four brain samples from patients with PML. Neither BK virus (BKV) nor simian virus 40 (SV40) DNA were detected in these samples. No evidence was found to support the hypothesis that polyomaviral DNA is present in the central nervous system of immunosuppressed patients without PML (CSF n = 67, brain n = 19). JCV DNA was not detected in any peripheral blood sample included in this study. JCV DNA was detected in urine from three of eight patients with PML, but was also amplified from three of 29 urine samples from patients without PML, JCV, and not SV40 or BKV, was associated with PML in this study.

BK Virus↗
PubMed1996

Effects on pulmonary function of two regimens of chemotherapy for AIDS related Kaposi's sarcoma.

We retrospectively analysed serial pulmonary function tests in 14 HIV infected patients receiving either bleomycin and vincristine or liposomal doxorubicin therapy (Doxil) for AIDS related Kaposi's sarcoma. There was a significant reduction in the carbon monoxide transfer coefficient in bleomycin treated patients compared with patients treated with Doxil. No other significant changes in pulmonary function, including the carbon monoxide diffusing capacity, were observed. These preliminary findings suggest that HIV infected patients with Kaposi's sarcoma, who are receiving bleomycin, may be at risk of accelerated pulmonary dysfunction. A larger prospective study should be performed to enable further investigation.

AIDS-Related Opportunistic Infections↗