PubMed Health⌕ Search

Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 19 recordsLinked to original sources
PubMed1998

Central pontine myelinolysis in AIDS.

Central pontine myelinolysis (CPM) is an uncommon complication in sick patients with severe underlying disorders such as chronic alcoholism, malignancy, malnutrition and hyponatraemia. We report two patients with advanced HIV infection who developed CPM. In one case the diagnosis was not suspected in life, in the other the diagnosis was made just before death, on the basis of magnetic resonance (MR) imaging appearances. At post mortem there was a close correlation between the MR abnormalities and the anatomic changes in the pons.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients with central nervous system complications of HIV-1 infection: a correlation with blood-brain-barrier dysfunction.

As nitric oxide (.NO) is hypothesised to play a role in the immunopathogenesis of neurological complications associated with inflammation, we compared levels of cerebrospinal fluid (CSF) and serum .NO metabolites in 24 patients with HIV-1 infection, to those in 58 non-HIV infected patients with neurological disorders. Levels of .NO metabolites were correlated with blood-brain-barrier dysfunction. CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. The .NO metabolites, nitrate and nitrite, were raised in the CSF and serum of patients with AIDS and central nervous system complications, when compared to non-HIV infected patients with inflammatory and non-inflammatory neurological disorders (median nitrate and nitrite: CSF=18.3 microM vs. 11.1 microM vs. 7.0 microM, P<0.001, and serum=53.8 microM vs. 50.3 microM vs. 41.4 microM, P=0.04, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient. This study supports the evidence that .NO is a potential mediator of blood-brain-barrier breakdown in inflammatory diseases of the central nervous system.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Mycobacterium kansasii and human immunodeficiency virus co-infection in London.

OBJECTIVES: although Mycobacterium kansasii infection has long been endemic in the U.K., the disease burden and characteristics of infection in the HIV-seropositive population has not been well documented. This study addresses these issues in an inner city population that comprises a quarter of all cases of acquired immunodeficiency syndrome (AIDS) reported in the U.K. METHODS: retrospective review of case notes from two inner London specialist HIV Units. RESULTS: twenty-nine cases of M. kansasii infection were identified, with case notes available for review in 26. Ten had pulmonary disease and nine had disseminated infection: a further seven patients appeared simply to be colonized (two respiratory and five gastrointestinal): M. kansasii was isolated from stool in over a third (nine of 26) of cases. Disseminated M. kansasii infection occurred in 0.44% of AIDS cases seen in our two units and all isolates were resistant to isoniazid ion vitro. A clinical response achieved in 11 of the 13 patients with M. kansasii-related disease who received anti-mycobacterial therapy. All four patients who relapsed following initial clinical response to therapy had received sub-optimal treatment. CONCLUSIONS: the incidence of disseminated M. kansasii infection in HIV-infected individuals in the U.K. is similar to that seen in those from high prevalence regions of the U.S.A., and anti-mycobacterial therapy leads to a clinical response in the majority of patients with HIV and M. kansasii co-infection. The frequent isolation of M. kansasii from the stool suggests that the gastrointestinal tract may be a significant source of disseminated infection.

Adult↗
PubMed1998

Plasmablastic lymphoma: a new subcategory of human immunodeficiency virus-related non-Hodgkin's lymphoma.

A patient with human immunodeficiency virus-related non-Hodgkin's lymphoma arising in the oral cavity is reported. The tumour had an unusual immunohistochemical profile that was negative for leucocyte common antigen and the B-cell antigen CD20 but positive for the plasma cell-reactive antibody VS38c. The features of this type of tumour, which has recently been categorized, are presented and discussed.

Adult↗
PubMed1998

Diagnostic utility of fine needle aspiration (FNA) cytology in HIV-infected patients with lymphadenopathy.

Sixty-five FNA cytology procedures were performed on lymph nodes in 52 HIV+ patients. Cervical lymph nodes were the commonest site of FNA cytology investigation (54%). The diagnoses were persistent generalized lymphadenopathy (38%), infection (17%), and malignancy (11%). Diagnosis could not be rendered in 25% of FNA cytology due to inadequate sampling. Of those with infection, mycobacterial disease was the commonest cause (91%), the diagnosis of which was enhanced by concurrent microbiological examination. Non-Hodgkin's lymphoma was the commonest malignancy. Sixteen lymph node FNA cytologies had subsequent tissue biopsy. There were two false-positive and four false-negative FNA cytologies. FNA cytology in HIV+ patients is most useful in the diagnosis of infection, obviating the need for tissue biopsy and allowing prompt initiation of treatment.

Adult↗
PubMed1998

Sequence polymorphisms in the Pneumocystis carinii cytochrome b gene and their association with atovaquone prophylaxis failure.

Atovaquone (Mepron, 566c80) is an effective agent against Pneumocystis carinii, which probably acts by binding to cytochrome b and inhibiting electron transport. To assess the possibility that atovaquone resistance might be developing, the genes for the cytochrome b from P. carinii sp. f. carinii and P. carinii sp. f. hominis were partially sequenced. Eight of 10 patient isolates had cytochrome b genes with the same amino acid sequence. The P. carinii cytochrome b genes from 2 of 4 patients who had atovaquone prophylaxis failure contained mutations resulting in amino acid changes in one of the ubiquinone (coenzyme Q) binding sites (Qo). These mutations are homologous to mutations in other microorganisms that confer resistance to similar inhibitors. Variations in the sequence of the P. carinii cytochrome b gene suggest but do not prove the development of drug resistance.

Amino Acid Sequence↗
PubMed1998

Detection of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus DNA in CSF from persons infected with HIV who had neurological disease.

OBJECTIVES: To determine the frequency and clinical relevance of Epstein-Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV) DNA detection in the CSF from patients infected with HIV. METHODS: Cerebrospinal fluid was obtained prospectively from 115 consecutive patients infected with HIV undergoing diagnostic lumbar puncture for investigation of neurological disease. Amplification of DNA was performed using a nested polymerase chain reaction (PCR) for detection of EBV internal repeat and KSHV minor capsid sequences. RESULTS: EBV DNA was detected in the CSF supernatant of 18 patients. This included all patients with primary CNS lymphoma (seven patients) or a combination of systemic and CNS lymphoma (two patients). By contrast EBV DNA was not detected in the CSF supernatant of any patient with systemic, but not CNS, lymphoma (10 patients). EBV DNA was also detected in the supernatant of nine further patients without a diagnosis of lymphoma at the time of lumbar puncture, two of whom subsequently developed CNS lymphoma. No EBV DNA was detected in CSF supernatant from the remaining 87 samples (two of these patients subsequently developed lymphoma). KSHV DNA was detected in the CSF of two patients, one had systemic (but not CNS) lymphoma and the other did not have lymphoma. CONCLUSION: A diagnosis of CNS lymphoma is strongly associated with the presence of EBV DNA in CSF. In the absence of clinical and radiological features of CNS lymphoma, the presence of detectable CSF EBV DNA may predict subsequent tumour development. KSHV DNA is rarely detected in CSF in this patient group and shows no correlation with lymphoma or other neurological disease.

AIDS Dementia Complex↗
PubMed1998

Association of Kaposi's sarcoma associated herpesvirus (KSHV) DNA in bronchoalveolar lavage fluid of HIV infected individuals with bronchoscopically diagnosed tracheobronchial Kaposi's sarcoma.

OBJECTIVES: To determine the frequency of detection of Kaposi's sarcoma associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, DNA in bronchoalveolar lavage (BAL) fluid from HIV infected individuals with and without KS and to compare this with the detection rate in peripheral blood. Also to identify whether KSHV was associated with specific cell types in lavage fluid. METHODS: Nested PCR was used to detect KSHV DNA in BAL fluid from 41 consecutive individuals with Kaposi's sarcoma (KS) and in 41 controls with similar CD4 lymphocyte counts. Semiquantification of viral DNA was by end point titration. A positive cell sorting selection procedure was used to isolate specific BAL fluid cell types. RESULTS: KSHV DNA was detected in BAL fluid from 24 of 29 (83%) individuals with a bronchoscopic diagnosis of tracheobronchial KS. None was detected in 12 individuals with only cutaneous KS, or in 41 matched controls without KS. In five, KSHV DNA was detected in the cell depleted and cellular fractions of BAL fluid and in 1/5 in the CD14 (macrophage) fractions. None was detected in the CD19 (B lymphocyte) or CD4/CD8 (T lymphocyte) fractions. CONCLUSIONS: There was a clear association between the diagnosis of tracheobronchial KS and detection of KSHV DNA in BAL fluid. The cell type supporting KSHV in the respiratory tract is not CD 19 positive and has yet to be conclusively identified.

Bronchial Neoplasms↗
PubMed1998

Presentation, pathology, and outcome of HIV associated renal disease in a specialist centre for HIV/AIDS.

OBJECTIVES: To describe the presentation, pathology, and outcome of biopsy proved renal disease in HIV infected patients at a central London HIV unit from 1992 to 1996. METHODS: Retrospective review of a computerised database and case notes to identify patients with renal disease confirmed by antemortem percutaneous renal biopsy or necropsy. RESULTS: 17 patients were identified, 13 had biopsy and four necropsy confirmed renal disease. Abnormalities included HIV associated nephropathy (HIVAN) in seven (41%) patients, membranous glomerulonephritis (GN) in four (23%), haemolytic uraemic syndrome (HUS) in two (12%), and interstitial nephritis, rhabdomyolysis, IgA nephropathy, and membranoproliferative GN in one patient each. Although renal disease was the first presentation of HIV disease in six (35%) patients the majority had advanced HIV disease (median CD4 count 40 x 10(6)/l). The commonest presentation was acute renal failure (ARF) in 10 (59%) patients, chronic renal failure (CRF) in five (29%), and proteinuria alone in two (12%). Although the majority of patients died during the study period (9/13) only three deaths were attributable to their renal disease. Survival ranged in those with HIVAN from 0 to 31 (median 10) months and, in those with membraneous GN from 1 to 46 (median 29) months. CONCLUSIONS: HIVAN was the commonest renal disease found in this group of patients; however, a variety of other pathologies were seen with variable outcomes. All cases of HIVAN were in patients of African or Afro-Caribbean origin and for the majority this was their first presentation of HIV disease. Nephrologists need to be aware of the possibility of HIV infection in patients presenting with renal disease.

AIDS-Associated Nephropathy↗
PubMed1998

Magnetic resonance imaging, thallium-201 SPET scanning, and laboratory analyses for discrimination of cerebral lymphoma and toxoplasmosis in AIDS.

OBJECTIVES: To compare the results of magnetic resonance imaging (MRI) and thallium-201 (201Tl) SPET scanning with laboratory analyses including CSF DNA detection, brain biopsy, and necropsy in the discrimination of cerebral lymphoma and toxoplasmosis in patients with AIDS. METHODS: A retrospective study of 32 patients infected with HIV who had focal CNS lesions on MRI as a result of either lymphoma or toxoplasmosis. RESULTS: 18 patients had lymphoma, 12 had toxoplasmosis, and two had both. Toxoplasma IgG antibodies were detected in only seven patients--four with toxoplasmosis, two with lymphoma, and one with both diagnoses. Epstein-Barr virus DNA was detected in CSF of all six patients with lymphoma and none of two with toxoplasmosis. MRI showed multiple lesions in 23 patients, appearances did not discriminate between lymphoma and toxoplasmosis; nine patients had single lesions, of these eight had lymphoma (p = 0.044, two tailed Fisher's exact test) 201Tl SPET showed accumulation in 17 with lymphoma and six with toxoplasmosis (p = 0.034, two tailed Fisher's exact test). Of nine patients with single lesions on MRI and 201Tl SPET with focal accumulation eight had lymphoma. 201Tl SPET uptake ratios of > or = 2.9 were only seen with lymphoma. CONCLUSION: Knowledge of patients' toxoplasma serostatus does not aid discrimination between lymphoma and toxoplasmosis. Single lesions on MRI with focal accumulation of 201Tl strongly suggest lymphoma. Multiple lesions on MRI with 201Tl SPET uptake ratios > or = 2.9 also suggest lymphoma; uptake ratios less than 2.1 do not aid discrimination. Detection of Epstein-Barr virus DNA in CSF is highly sensitive and specific for cerebral lymphoma.

AIDS-Related Opportunistic Infections↗
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

The measurement of R2, R2* and R2' in HIV-infected patients using the prime sequence as a measure of brain iron deposition.

Brain iron deposition was assessed at 1.5 T in the caudate nucleus, globus pallidus and frontal and parieto-occipital white matter in 28 human immunodeficiency virus (HIV)-infected patients and 15 control subjects with a new Partially Refocussed Interleaved Multi-Echo sequence by measuring 1/T2, 1/T2* and 1/T2' (i.e., R2, R2* and R2'). There were significant differences in the R2 and R2* of the caudate nucleus (p < 0.0001 and p < 0.05) and the R2, R2* and R2' of the globus pallidus (p < 0.01, p < 0.005 and p < 0.05) in HIV-infected patients compared to control subjects. There was a trend for higher values of R2, R2* and R2' in the globus pallidus and caudate nucleus in HIV-infected patients with later stage HIV disease. These results suggest that there is greater iron deposition in the basal ganglia of HIV-infected patients compared with control subjects, with a predilection for the globus pallidus. The relationship between iron deposition in the brain and various parameters of severity of HIV infection remains uncertain.

AIDS Dementia Complex↗