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Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 37 records · Page 2Linked to original sources

Diagnostic utility of bone marrow sampling in HIV-infected patients since the advent of highly active antiretroviral therapy.

We investigated the diagnostic value of bone marrow (BM) sampling in investigation of HIV-infected patients presenting to a major London HIV treatment centre between 1999 and 2004. One hundred and fourteen consecutive patients underwent 130 BM samplings. The majority of BM aspirates were normal or showed non-diagnostic changes; microscopy revealed lymphoma in one and mycobacterial infection in two. Subsequent culture identified mycobacterial infection in nine samples. BM trephine had a diagnostic yield of 26% in patients with fever and cytopaenia (including mycobacteriosis in 14%, lymphoma in 6%, Castleman disease in 3% and "drug effect" in 3%), a yield of 20% in patients with fever, but no cytopaenia (mycobacteriosis in each case), and a yield of 19% in patients with cytopaenia in the absence of fever (lymphoma in 5% and "drug effect" in 14%). In investigation/staging of lymphoma, the diagnostic yield was 36%. The overall yield from BM sampling was 30% in patients receiving highly active antiretroviral therapy (HAART) and 23% in those not receiving HAART. In this study, BM sampling was of most diagnostic value in HIV-infected patients where fever and cytopaenia coexisted in the absence of localizing signs of infection, and in the staging/investigation of lymphoma. BM sampling had less diagnostic value in the investigation of fever without cytopaenia or cytopaenia without fever.

AIDS-Related Opportunistic Infections↗

Pneumonia complicating Shigella sonnei dysentery in an HIV-infected adult male.

An HIV-1-infected adult presented with a short history of dyspnoea, productive cough and myalgia with fever. Shortly after presentation, he developed the abrupt onset of high-volume watery diarrhoea: stool culture grew Shigella sonnei. At the same time, he became hypoxaemic, and thoracic imaging showed bilateral lower lobe consolidation/collapse. Culture of sputum and blood was negative. The patient recovered with fluid resuscitation and ciprofloxacin monotherapy. This is the first reported case of pneumonia complicating S. sonnei dysentery in an HIV-infected adult.

Adult↗

Imaging features of multicentric Castleman's disease in HIV infection.

AIM: To describe the computed tomography (CT) features of human immunodeficiency virus (HIV)-associated Castleman's disease. MATERIALS AND METHODS: Nine HIV-positive patients with biopsy-proven Castleman's disease were studied. Clinical and demographic data, CD4 count, histological diagnosis and human herpes type 8 (HHV8) serology or immunostaining results were recorded. CT images were reviewed independently by two radiologists. RESULTS: CT findings included splenomegaly (n=7) and peripheral lymph node enlargement (axillary n=8, inguinal n=4). All nodes displayed mild to avid enhancement after intravenous administration of contrast material. Hepatomegaly was evident in seven patients. Other features included abdominal (n=6) and mediastinal (n=5) lymph node enlargement and pulmonary abnormalities (n=4). Patterns of parenchymal abnormality included bronchovascular nodularity (n=2) consolidation (n=1) and pleural effusion (n=2). On histological examination eight patients (spleen n=3, lymph node n=9, lung n=1, bone marrow n=1) had the plasma cell variant and one had mixed hyaline-vascular/plasma cell variant. The majority had either positive immunostaining for HHV8 or positive serology (n=8). CONCLUSION: Common imaging features of multicentric Castleman's disease in HIV infection are hepatosplenomegaly and peripheral lymph node enlargement. Although these imaging features may suggest the diagnosis in the appropriate clinical context, they lack specificity and so biopsy is needed for diagnosis. In distinction from multicentric Castleman's disease in other populations the plasma cell variant is most commonly encountered, splenomegaly is a universal feature and there is a strong association with Kaposi's sarcoma.

Adult↗

Immune reconstitution inflammatory syndrome in HIV-infected patients with mycobacterial infections starting highly active anti-retroviral therapy.

AIM: To describe the radiological appearances of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected patients with mycobacterial infections starting highly active anti-retroviral therapy (HAART). MATERIALS AND METHODS: Five consecutive HIV infected patients with IRIS due to mycobacterial infection were studied. Intercurrent infection and poor drug compliance were excluded as causes of presentation. The chest radiological appearances at the time of starting HAART and at the time of diagnosis of IRIS were compared. RESULTS: In these five patients there was clinical and radiological deterioration, occurring between 10 days and 7 months after starting HAART, leading to unmasking of previously undiagnosed mycobacterial infection or to worsening of mycobacterial disease. All five patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions in peripheral blood HIV "viral load". Chest radiographic abnormalities due to IRIS included marked mediastinal lymphadenopathy in three patients-severe enough to produce tracheal compression in two patients (one of whom had stridor)-and was associated with new pulmonary infiltrates in two patients. The other two patients had new infiltrates, which in one patient was associated with a pleural effusion. CONCLUSION: These cases illustrate the diverse chest radiographic appearances of IRIS occurring after HAART in patients with mycobacterial and HIV co-infection. Marked mediastinal lymphadenopathy occurred in three of these five patients (with associated tracheal narrowing in two patients); four patients developed pulmonary infiltrates and one had an effusion. The cases further highlight that the onset of IRIS may be delayed for several months after HAART is started.

AIDS-Related Opportunistic Infections↗

Expression and complexity of the PRT1 multigene family of Pneumocystis carinii.

Pneumocystis carinii has a multigene family, PRT1, that encodes proteins with homology to KEX2-like proteases. PRT1 genes cluster with MSG genes near the telomeres and, like MSG, PRT1 proteins seem to be surface-expressed. The clustering of PRT1 and MSG genes suggested that expression of the two multigene families might be coordinated. Studying gene expression in P. carinii has been hampered by the lack of a culture system, and by lack of clonality in P. carinii populations in naturally infected rats, the host of this fungus. Heterogeneity can be reduced, however, by low-dose intratracheal inoculation, which can produce P. carinii populations dominated by organisms derived from a single progenitor. To study PRT1 expression, nude rats were inoculated with approximately 10 P. carinii each. The clonality of the P. carinii populations from inoculated rats was assessed by analysis of the UCS locus, a site in the genome that is known to be very heterogeneous in naturally infected rats, but nearly homogeneous in rats infected by low-dose intratracheal inoculation. Each of the populations had the same MSG gene at the UCS locus in at least 80 % of the organisms. To investigate PRT1 gene expression, RNA was amplified using primers that amplify numerous PRT1 genes. Seventy-four cloned cDNAs were sequenced, including at least 12 clones from each population of P. carinii. Many differently expressed PRT1 sequences were identified in each population, and a total of 45 different sequences were detected. However, the same PRT1 sequence was present in 15 of 74 plasmids and was found in 3 of the 5 P. carinii populations, suggesting that some PRT1 genes may be either more commonly expressed or expressed at a higher level. These data show that many members of the PRT1 gene family can be expressed in populations of P. carinii derived from few progenitors and suggest that the regulation of this family is different from that governing expression of the MSG gene family.

Animals↗

Unusual muscle disease in HIV infected patients.

Two patients presented with proximal muscle weakness, a normal or minor elevation of creatine phosphokinase (CPK) and normal findings on electromyography. Muscle biopsy in one patient revealed CD8+ polymyositis, and in the other showed ddI induced myopathy. These cases illustrate the importance of muscle biopsy in identifying the underlying pathology in HIV infected patients with muscle weakness and little or no abnormality in laboratory investigations.

Anti-HIV Agents↗

Fever in the recently returned HIV infected traveller.

A 41 year old HIV infected man with an extensive travel history developed intermittent fever and weight loss shortly after returning from abroad. Extensive and prolonged investigation identified the cause.

AIDS-Related Opportunistic Infections↗

Diagnosis of Chlamydia trachomatis in North Thames region 2003.

A multi-centre re-audit of tests used for chlamydia diagnosis in GU medicine clinic attendees from February 2003 to March 2003 in the North Thames region showed improvements since our previous audit in 1999, with a significant increase in the proportion of clinics using nucleic acid amplification tests and non-invasive testing.

Ambulatory Care Facilities↗

Treatment of Chlamydia trachomatis in North Thames region 2003.

Following on from the survey of techniques used for testing chlamydia, a multi-centre re-audit of the treatment of C. trachomatis in genitourinary clinic attendees in the North Thames region from February to March 2003 was performed. This showed an improvement since our previous audit with a significant increase in the number of centres following national guidelines in antibiotic prescribing and offering test of cure in clinically indicated cases.

Ambulatory Care Facilities↗

Human immunodeficiency virus type 1-related pulmonary Mycobacterium xenopi infection: a need to treat?

We report treatment decisions and outcomes for 20 patients who were infected with human immunodeficiency virus type 1 (HIV-1) and were receiving highly active antiretroviral therapy (HAART) who had respiratory symptoms and from whom Mycobacterium xenopi was isolated. All patients also had coexisting pulmonary pathologic conditions. The median blood T cell CD4 count was 37 cells/microL (range, 2-480 cells/microL). Fifteen of 20 patients received no antimycobacterial therapy and remain healthy after a median of approximately 4 years of follow-up, and 2 patients required treatment specifically for M. xenopi infection, both showing clinical improvement. We conclude that pulmonary M. xenopi isolation in HIV-1 patients receiving HAART does not usually require specific treatment.

AIDS-Related Opportunistic Infections↗

Lymphocytic interstitial pneumonitis in HIV infected adults.

OBJECTIVES: To describe current knowledge on the aetiology, pathology, presentation, diagnosis, and treatment of lymphocytic interstitial pneumonitis in HIV infected adults. METHODS: A Medline search was performed using the key words "HIV," "pneumonitis," and "lymphocytes." A further search was performed with the MESH heading "interstitial lung disorders." Related articles were also searched using Pubmed. RESULTS: Lymphocytic interstitial pneumonitis is a common complication in HIV infected children. In adults it is uncommon and is described most commonly among black African and Afro-Caribbean patients. The aetiology and pathogenesis of lymphocytic interstitial pneumonitis in HIV infection is not clear. The clinical and radiological presentations may be indistinguishable from Pneumocystis carinii infection and a lung biopsy is necessary to establish the diagnosis. Recent evidence suggests that lymphocytic interstitial pneumonitis in HIV infected patients may respond to combination antiretroviral therapy with dramatic improvements in clinical and radiological abnormalities. CONCLUSION: Lymphocytic interstitial pneumonitis in HIV infected patients is a treatable condition. This condition should be considered in HIV infected patients presenting with respiratory symptoms as they may gain considerable benefit from antiretroviral therapy.

Adult↗

Central pontine myelinolysis complicating treatment of multicentric Castleman's disease and Kaposi's sarcoma in a patient with AIDS.

An HIV positive black African woman presented with widespread lymphadenopathy and pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed both Kaposi's sarcoma and multicentric Castleman's disease. Despite antiretroviral therapy and chemotherapy the patient deteriorated, developing confusion and dysphasia. A cranial magnetic resonance scan showed central pontine myelinolysis. Despite supportive therapy the patient died.

AIDS-Related Complex↗

Polymyositis masquerading as mitochondrial toxicity.

A 66 year old HIV infected male heavy smoker presented with arthralgia, myalgia, and weight loss which was originally ascribed to nucleoside induced mitochondrial toxicity. Despite withdrawal of antiretroviral therapy a proximal myopathy developed. Further investigation excluded malignancy. Polymyositis was diagnosed on muscle biopsy. The patient recovered completely with oral prednisolone. This case highlights the importance of muscle biopsy in HIV infected patients whose myopathy persists despite withdrawal of antiretroviral therapy and the need for thorough investigation of non-specific symptoms in HIV infected patients who are receiving antiretroviral therapy.

Aged↗

Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study.

BACKGROUND: The opportunistic fungus Pneumocystis jiroveci is a common cause of respiratory infection in immunocompromised patients. By contrast, pneumocystis pneumonia (PCP) occurs only rarely in immunocompetent individuals. Asymptomatic colonisation with P jiroveci has recently been described in patients who are either minimally immunosuppressed or who have underlying lung disorders such as bronchiectasis. We sought to determine the prevalence of asymptomatic colonisation by P jiroveci in a cohort of adult patients undergoing diagnostic bronchoscopy. METHODS: A prospective observational cohort study was performed in patients who required bronchoscopy and bronchoalveolar lavage (BAL) as part of their routine clinical assessment. All the samples underwent standard microbiological analysis and a Grocott methenamine silver stain was performed where clinically indicated to detect the presence of P jiroveci. Polymerase chain reaction for detection of P jiroveci specific DNA was also performed. RESULTS: Ninety three consecutive BAL fluid samples were analysed, 17 (18%) of which contained P jiroveci DNA. Of the potential predictors examined, only glucocorticoid use was significantly associated with detectable P jiroveci DNA. Eighteen patients were receiving oral glucocorticoids (equivalent to >20 mg/day prednisolone) at the time of bronchoscopy, of whom eight (44%) had detectable P jiroveci DNA. In contrast, P jiroveci was detected in only nine of 75 patients (12%) who were not receiving glucocorticoids (difference between proportions 32%, 95% CI 8 to 57; p=0.004, two tailed Fisher's exact test). CONCLUSIONS: P jiroveci colonisation, as determined by detection of P jiroveci DNA in BAL fluid, is common in HIV negative patients with primary respiratory disorders undergoing bronchoscopy and BAL. The higher prevalence in patients receiving corticosteroids suggests that oral glucocorticoid therapy is an independent risk factor for colonisation. In contrast, underlying lung cancer or COPD did not appear to be risk factors.

Adult↗

Management of HIV and hepatitis B or C co-infection in 15 HIV treatment centres. Disparity between protocols and practice.

Our aim was to ascertain current guidelines and clinical practices prevalent in HIV treatment centres in the North Thames Region of England on the care of patients co-infected with HIV and hepatitis B or C. A self-completed postal survey of clinic guidelines and retrospective case-note reviews was performed. Fifteen of the 27 units completed the survey and generally had clinic guidelines consistent with current national guidelines. Stated policy was usually to screen HIV patients for hepatitis B virus (HBV) and hepatitis C virus (HCV) and to offer specific therapy for the hepatitis as well as the HIV. Many units were unable to contribute cases to the case-note review, probably through lack of case-identification, and therefore 11 units contributed 27 case-note reviews on HIV/HBV and five units contributed 11 case-note reviews on HIV/HCV. Fifty-six percent (25/45) of patients of HBV patients were HBeAg+ve and 88% (22/25) of these had received specific hepatitis B therapy although for 59% (13/22) this was with lamivudine as part of a highly active antiretroviral therapy regimen. None of the HIV/HCV patients had received or been referred for HCV-specific therapy. Testing for hepatitis A immunity in HBV or HCV patients with a view to vaccination was done in only 50% although 96% of HIV/HCV patients had been screened for HBV. There are significant differences between the clinics' intended and actual management of HIV and chronic viral hepatitis co-infection.

Ambulatory Care Facilities↗