Avascular necrosis in HIV patients: a case-control study.

This study investigates the association of avascular necrosis (AVN) in human immunodeficiency virus (HIV)-positive individuals with possible risk factors, including antiretroviral therapy. Clinic records of all AVN cases diagnosed up to July 2009 in HIV-positive patients attending North Middlesex Hospital, London, UK were retrospectively reviewed. For each case, one control was randomly selected, matched for gender, age, nadir CD4 count and date of HIV diagnosis. Of 15 symptomatic AVN cases identified, eight were in women. Univariate analysis demonstrated significant associations between AVN and a history of systemic steroid use (p = 0.004) and cumulative exposure to protease inhibitor (p = 0.03). Physicians should be aware of the risk of AVN with steroid use, the importance of early diagnosis and avoidance of other risk factors in order to prevent further joint involvement if possible.

Discontinuation of non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy due to nucleoside analogue reverse transcriptase inhibitor-related metabolic toxicity.

We aimed to evaluate the reasons for, and timing of, treatment changes in a cohort of treatment-naïve patients initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing highly active antiretroviral therapy (HAART). All 268 patients initiating these regimens between January 1998 and September 2003 were included. Median follow up was 103 weeks. The median baseline CD4 count was 150 cells/microL. Seven patients (3%) died and 155 patients (58%) experienced a change in their HAART regimen. The reasons drugs were discontinued included toxicity in 106 patients (40%), virological failure in 21 (8%), other reasons in 23 (9%) and unknown reasons in five (2%). Fifty-one patients (19%) stopped NRTIs due to peripheral neuropathy, hyperlactataemia, lipoatrophy, lipodystrophy or myelosuppression, and these events were more likely in patients with baseline CD4 count below the median (P = 0.039). The findings in this cohort show that discontinuation of HAART was commonly due to toxicity, especially metabolic or mitochondrial toxicity in those with lower baseline CD4 count.

An association of disseminated Mycoplasma fermentans in HIV-1 positive patients with non-Hodgkin's lymphoma.

We examined the relationship between the haematogenous dissemination of Mycoplasma fermentans and non-Hodgkin's lymphoma (NHL) in 265 HIV-1 positive patients. A polymerase chain reaction (PCR) assay was used to detect M. fermentans in peripheral blood mononuclear cells (PBMCs) from 50 patients enrolled consecutively from an HIV outpatient clinic in 1991 (cohort 1), 56 patients with lower respiratory tract infection who underwent bronchoscopy in 1992 (cohort 2), and 159 patients who were enrolled into a natural history cohort study in 1994 (cohort 3). The incidence of NHL among the patients was determined in 1998. The PBMCs of 29 patients (10.9%) were positive for M. fermentans (8 in cohort 1, 13 in cohort 2 and 8 in cohort 3) and 11 patients (4.2%) developed NHL which was confirmed histologically (3 in cohort 1, 4 in cohort 2 and 4 in cohort 3). We found a statistically significant association between the presence of M. fermentans and the development of NHL in the combined cohort (risk ratio [RR]=6.78 [95% confidence interval (CI) 2.21--20.84], P=0.003 Fisher's exact test [FET]). This association remained significant even after adjustment in a multivariate analysis for CD4 cell count and HIV disease status at the time of M. fermentans testing (RR=7.97 [95% CI=2.16--29.47], P=0.002).

Disseminated Mycoplasma fermentans in AIDS patients: several case reports.

We describe the clinical course of 2 HIV-positive patients in whom Mycoplasma fermentans was disseminated and persistent. We identified individuals in whom M. fermentans had been detected in a peripheral blood mononuclear cell (PBMC) or bronchoalveolar lavage (BAL) specimen. Of this group a number had archival specimens of interest: liver and/or bone marrow, taken to investigate a systemic illness, and a few had M. fermentans positive tissues. Two patients, NC and DP, had recurrent episodes of lower respiratory tract infection and fever and both had been investigated by bronchoscopy on 4 occasions. M. fermentans was detected in specimens taken 18 and 27 months apart for NC and DP respectively, and in between, and repeatedly in respiratory tract tissues of DP. Granuloma were identified in the liver of NC that was M. fermentans positive but no further evidence of opportunistic infection was found during his illness. Both patients had M. fermentans positive bone marrow specimens. Assessment of the patients' records suggested that in one patient M. fermentans may have contributed to the respiratory disease and in the other to the systemic disease.

Detection of Mycoplasma fermentans in healthy students and patients with congenital immunodeficiency.

OBJECTIVES: To determine the prevalence of M. fermentans at different anatomical sites in healthy subjects and in patients with congenital immunodeficiency, and to determine whether haematogenous invasion occurs among the latter. METHODS: A polymerase chain reaction (PCR) assay was used to detect M.fermentans in throat swabs and urine specimens from healthy students, and from patients with congenital immunodeficiency. Peripheral blood mononuclear cells (PBMCs) from the latter group were also tested. RESULTS: Sixty-two students provided throat swabs, of which 11 (18%) were M. Jermentans-positive; 46 provided urine specimens, of which eight (17%) were positive. Of the 45 students who provided both throat and urine specimens, 12 (27%) had M. fermentans-positive samples; four in the throat and urine, four in the throat only and four in the urine only. Nineteen of the 20 patients with congenital immunodeficiency provided throat swabs, of which one (5%) was M. fermentans-positive; 19 also provided urine specimens, of which three (16%) were positive. All of the immunodeficient patients provided a PBMC sample, but none was positive. CONCLUSION: M. fermentans occurred frequently at mucosal sites in a healthy population and in subjects with congenital immunodeficiency. However, such a deficiency did not lead to overt haematogenous invasion.

Mycoplasma species in rapid and slow HIV progressors.

We determined the relationship between the presence of Mycoplasma fermentans and Mycoplasma penetrans and the rate of progression of HIV-associated disease in a nested case-control study based on a cohort of 159 HIV-infected patients with different rates of disease progression. Study participants were divided into 3 progression groups: non-progressors who had been HIV-1 seropositive for at least 9 years and had remained asymptomatic with a CD4 cell count of > 500/mm3; slow progressors who had been HIV-1 seropositive for at least 9 years and whose CD4 cell count had fallen below 500 cells, and who had developed symptomatic disease or AIDS; and rapid progressors who had developed AIDS within 5 years of HIV infection. Peripheral blood mononuclear cells (PBMCs) were collected at enrollment and examined by mycoplasma polymerase chain reaction (PCR) assays. Three (7%) of 46 non-progressors, 3 (3%) of 86 slow progressors, and 2 (7%) of 27 rapid progressors were M. fermentans positive. The PBMCs from 91 subjects were tested for M. penetrans DNA and none was positive. The small proportion of M. fermentans-positive patients indicates that the mycoplasma cannot be important in the development of AIDS in the large majority of patients. Furthermore, no association was found between its presence and more rapid HIV disease progression.

Detection of Mycoplasma fermentans in broncho-alveolar lavage fluid specimens from AIDS patients with lower respiratory tract infection.

OBJECTIVE: To investigate the role of Mycoplasma fermentans in lower respiratory tract disease of HIV-positive patients. METHODS: A polymerase chain reaction (PCR) assay was used to detect M. fermentans in broncho-alveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) collected from 78 hospitalized HIV-positive patients with lower respiratory tract disease (the index group). BAL specimens were also assessed from two control groups; 25 HIV-positive patients without respiratory symptoms and 46 patients with a respiratory illness who did not have risk factors for HIV. RESULTS: Seventy-one (91%) of the 78 patients who comprised the index group had AIDS. Sixty-one patients provided BAL and PBMC specimens; 16 provided a BAL specimen and one only a PBMC specimen; 15 (25%) of the 61 patients had M. fermentans positive BAL fluid, of whom 10 (67%) also had a positive PBMC specimen. In contrast, of the 46 patients who had a negative BAL fluid, only three (6.4%) had a positive PBMC sample (P < 0.00001 Fisher's exact test). Overall, 21 (27%) of 77 patients had M. fermentans positive BAL fluid. Of these positive patients, 16 also had another microorganism in the BAL fluid and for five patients M. fermentans was detected alone. Compared with patients in the index group, none of the 46 BAL fluid specimens from patients at low risk of HIV infection was M. fermentans positive (P < 0.001, chi2 15.13). Two (8%) of the 25 HIV-positive patients without respiratory symptoms had a M. fermentans positive BAL fluid, positivity that was also statistically different from the index group (P = 0.045, chi2 4.01). CONCLUSIONS: M. fermentans frequently invades the lower respiratory tract of AIDS patients as an opportunist and may cause disease in some.

1H MR spectroscopy of the brain in HIV-1-seropositive subjects: evidence for diffuse metabolic abnormalities.

PURPOSE: To analyze brain metabolite changes in HIV-1-seropositive subjects in order to define whether the neuronal impairment is a localized or more diffuse process. MATERIALS AND METHODS: 15 patients and 18 volunteers underwent multivoxel proton magnetic resonance (MR) spectroscopy at 1.5T. Nine patients were classified as being neuropsychiatrically unimpaired and six as having HIV-1-associated dementia on the basis of a full neuropsychological examination. Spectra were analysed from multiple voxels located in the fronto-parietal cortex and white matter at the level of centrum semiovale. RESULTS: A significant reduction in mean peak area ratios of NAA/Cr (p<0.005 in the grey matter, p<0.01 in the white matter) and an elevation in mean Cho/Cr (p<0.005 in both grey matter and white matter) were observed in patients with HIV-1-associated dementia when compared to healthy volunteers. No significant metabolite abnormalities were detected in the neuropsychiatrically unimpaired group, although there was a similar trend in the metabolite ratios. The changes in metabolite ratios were of the same order of magnitude in the cortical grey matter and subcortical white matter as in the deeper white matter in all patients. There were also no significant regional variations in mean metabolite ratios between right and left hemispheres or anterior and posterior voxels at the level of the brain studied. There were no abnormalities in Glx/Cr in any spectra analysed from either patient group. CONCLUSION: The absence of significant regional variation in metabolite ratios at the level of the centrum semiovale provides some evidence that abnormalities of cerebral metabolites in HIV-infected patients may be part of a diffuse process.

General practitioners' immediate management of men presenting with urethral symptoms.

OBJECTIVES: To describe the immediate reported management, by general practitioners (GPs), of men presenting with symptoms of urethral discharge, or dysuria only. SUBJECTS: All 692 GPs in practice in Brent, Harrow, Ealing, Hammersmith, and Hounslow (UK). METHOD: Data were collected using a GP completed questionnaire concerning the management of the last male patient seen, aged less than 40 years, complaining of urethral discharge, and the last male patient under 40 years complaining of dysuria only. RESULTS: The response rate among GPs was 52%. Fifty three per cent of men with urethral symptoms, 86% of men with a urethral discharge and 24% with dysuria only, were identified by GPs and referred without investigation or treatment to a genitourinary medicine clinic. Of men with dysuria only, 93% of investigations by GPs were reported to include a mid-stream urine (MSU) specimen for bacteriology, and 19% a urethral swab for chlamydia. Seventy eight per cent of GPs reported using treatments with a broad spectrum antibiotic, 53% with trimethoprim, whilst 14% of GPs reported using a tetracycline in common use to treat non-gonococcal urethritis. Urine specimens were reported to be "culture positive" in 41% of men who had an MSU specimen tested, and 15% of men who had a urethral swab tested were reported to be chlamydia positive. CONCLUSION: The GPs included in this study were not a full sample, or representative of all the GPs, and the data are retrospective. Nevertheless, we found a large difference in GPs reported management for men with urethral symptoms according to whether or not urethral discharge was a reported complaint. Reported management is likely to be, at least, indicative of actual management. Therefore, the results suggest that assessment by GPs of men presenting with dysuria should be explored and more appropriate management strategies defined.

Mycoplasma fermentans and HIV-associated nephropathy.

We describe a patient in whom HIV-associated nephropathy developed in association with the detection of Mycoplasma fermentans. This mycoplasma was found in renal tissue by means of a polymerase chain reaction when nephropathy was first evident, and subsequently in urine, blood and the throat. The evidence presented strengthens the causal association of this micro-organism with HIV-induced nephropathy.

Proton MR spectroscopy of the brain in AIDS dementia complex.

Proton MR spectroscopy of the brain has been undertaken in 8 healthy volunteers and in 11 patients with human immunodeficiency virus infection and varying stages of AIDS dementia complex (ADC). Spectral appearances in patients with no ADC or early ADC were not significantly different from normal volunteers. Spectra from patients with moderate to severe ADC exhibited significant reductions in levels of N-acetyl aspartate (NAA) relative to creatine (Cr) and also showed elevations in choline containing compounds (relative to Cr). Because NAA is though to be a metabolic marker for normally functioning neurons, these findings suggest the presence of neuronal injury or loss in moderate to severe ADC. The significance of these findings is discussed.

Disseminated pneumocystis carinii infection in AIDS.

Eight patients with AIDS and Pneumocystis carinii infection were studied. Protean manifestations were a feature not untypical of disseminated pneumocystosis. Aerosolised pentamidine as prophylaxis against P carinii pneumonia was ineffective at suppressing dissemination. The knowledge that extrapulmonary infection can occur has implications for the detection and treatment of, and prophylaxis against, P carinii infection. The survival of patients with disseminated pneumocystosis is particularly poor, and may be due to a lack of clinical awareness and consequent delay in diagnosis.

Changes in urate metabolism after castration of patients suffering from carcinoma of the prostate.

13 patients with carcinoma of the prostate were investigated on a low purine diet before and after surgical castration, performed to slow progression of their disease. A control group of herniorrhaphy patients was similarly studied. The 2 groups were very similar pre-operatively except for urea which was higher pre-operatively in patients than controls (p0.004). Testosterone levels fell significantly in patients soon after surgery (W0.002). There was a significant fall in serum uric acid in the early post-operative phase in both patients (W0.004) and controls (W0.01) but the fall only remained significant one month after surgery in castrated patients (W0.007). Urinary uric acid levels in patients fell significantly soon after surgery (W0.04). This is a small study but results suggest that endogenous male hormones are at least partially responsible for serum uric acid levels since castration, with reduction in circulating testosterone, resulted in a fall in these levels.