Spending money to save money.
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Chlamydia Infections↗
Biomedical subjects
M Shahmanesh
Publications and source records attributed to M Shahmanesh.
Progressive intrathoracic lymphadenopathy: EBV associated non-Hodgkin's lymphoma.
A 30 year old man presented with late stage HIV disease and intrathoracic lymphadenopathy. Histology of a mediastinal biopsy suggested infective follicular hyperplasia or a peripheral T cell lymphoma. Subsequently, Epstein-Barr virus (EBV) infection was demonstrated in lymphocytes in the biopsy. Later, hepatosplenomegaly and peripheral lymphadenopathy developed. Histology of a cervical lymph node biopsy showed EBV associated diffuse large B cell (non-Hodgkin's) lymphoma.
AIDS-Related Opportunistic Infections↗
Lactic acidosis and abnormal liver function in advanced HIV disease.
A 48 year old man receiving HAART presented with late stage HIV disease, non-specific symptoms, a normal sized liver, ascites, and lactic acidosis. Following a failed liver biopsy worsening acidosis developed, requiring ICU support. Progressive liver failure occurred. Endoscopy showed oesophageal varices and a transjugular liver biopsy showed non-cirrhotic cholestasis; findings that were ascribed to HAART.
Acidosis, Lactic↗
Ethnicity and STIs: more than black and white.
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Black or African American↗
Why common things are common: the tale of non-gonococcal urethritis.
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Animals↗
Protease inhibitor related type III hyperlipoproteinaemia is common and not associated with apolipoprotein-E E2/E2 phenotype.
OBJECTIVE: To determine the prevalence of type III hyperlipoproteinaemia in a cohort of HIV infected patients taking protease inhibitors and its correlation with the apolipoprotein-E2 isoform. DESIGN: Cross sectional study of 57 consecutive HIV infected subjects taking protease inhibitor therapy for a median of 12.5 (1-29) months, seen in an outpatient HIV clinic. Controls were 17 patients on non-nucleoside reverse transcriptor inhibitor therapy (NNRTI) for 9 (1-19) months and 50 antiviral naive patients. METHODS: Fasting cholesterol, triglyceride, HDL cholesterol, lipoprotein (a), and glucose were measured. Lipoprotein electrophoresis was performed on patients with a cholesterol >6.5 mmol/l and a triglyceride concentration of >4.5 mmol/l. Apolipoprotein-E phenotype was determined in serum. RESULTS: Dyslipidaemia was found in 43 (75%) PI treated patients-37 with triglyceride >2.3 mmol/l, 30 with cholesterol >6.5 mmol/l, and nine with HDL cholesterol <0.9 mmol/l. 38% had a lipoprotein (a) >300 mg/l. 11 patients (19.3%) had a type III hyperlipoproteinaemia pattern. Only one was homozygous for the E2 phenotype and none had clinical diabetes. An additional patient had a serum lipid profile compatible with type III hyperlipoproteinaemia and an E3/E2 phenotype in whom electrophoresis was not carried out before treatment. Six (35%) of the NNRTI and 16 (32%) of the antiviral naive patients had dyslipidaemia. 18 (31.6%) of the PI and none of the control patients had a cholesterol and/or triglyceride >8 mmol/l. CONCLUSION: Type III hyperlipoproteinaemia is common in this group of patients and need not be associated with the apolipoprotein-E2/E2 isoform. HIV protease inhibitors may interfere with lipoprotein receptor related protein.
Adult↗
Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.
Patients with glucocorticoid excess develop central obesity, yet in simple obesity, circulating glucocorticoid levels are normal. We have suggested that the increased activity and expression of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) generating active cortisol from cortisone within adipose tissue may be crucial in the pathogenesis of obesity. In this study primary cultures of human hepatocytes and adipose stromal cells (ASC) were used as in vitro models to investigate the tissue-specific regulation of 11betaHSD1 expression and activity. Treatment with tumor necrosis factor-alpha (TNFalpha) caused a dose-dependent increase in 11betaHSD1 activity in primary cultures of both sc [1743.1 +/- 1015.4% (TNFalpha, 10 ng/ml); P < 0.05 vs. control (100%)] and omental [375.8 +/- 57.0% (TNFalpha, 10 ng/ml); P < 0.01 vs. control (100%)] ASC, but had no effect on activity in human hepatocytes [90.2 +/- 2.8% (TNFalpha, 10 ng/ml); P = NS vs. control (100%)]. Insulin-like growth factor I (IGF-I) caused a dose-dependent inhibition of 11betaHSD1 activity in sc [49.7 +/- 15.0% (IGF-I, 100 ng/ml]; P < 0.05 vs. control (100%)] and omental [71.6 +/- 7.5 (IGF-I, 100 ng/ml); P < 0.01 vs. control (100%)] stromal cells, but not in human hepatocytes [101.8 +/- 15.7% (IGF-I, 100 ng/ml); P = NS vs. control (100%)]. Leptin treatment did not alter 11betaHSD1 activity in human hepatocytes, but increased activity in omental ASC [135.8 +/- 14.1% (leptin, 100 ng/ml); P = 0.08 vs. control (100%)]. Treatment with interleukin-1beta induced 11betaHSD1 activity and expression in sc and omental ASC in a time- and dose-dependent manner. 15-Deoxy-12,14-PGJ2, the putative endogenous ligand of the orphan nuclear receptor peroxisome proliferator-gamma, significantly increased 11betaHSD1 activity in omental cells [179.7 +/- 29.6% (1 microM); P < 0.05 vs. control (100%)] and sc [185.3 +/- 12.6% (1 microM); P < 0.01 vs. control (100%)] ASC, and it is possible that expression of this ligand may ensure continued cortisol generation to permit adipocyte differentiation. Protease inhibitors used in the treatment of human immunodeficiency virus infection are known to cause a lipodystrophic syndrome and central obesity, but saquinavir, indinavir, and neflinavir caused a dose-dependent inhibition of 11betaHSD1 activity in primary cultures of human omental ASC. 11betaHSD1 expression is increased in human adipose tissue by TNFalpha, interleukin-1beta, leptin, and orphan nuclear receptor peroxisome proliferator-gamma agonists, but is inhibited by IGF-I. This autocrine and/or paracrine regulation is tissue specific and explains recent clinical data and animal studies evaluating cortisol metabolism in obesity. Tissue-specific 11betaHSD1 regulation offers the potential for selective enzyme inhibition within adipose tissue as a novel therapy for visceral obesity.
11-beta-Hydroxysteroid Dehydrogenases↗
Geomapping of chlamydia and gonorrhoea in Birmingham.
OBJECTIVE: To investigate if the core population hypothesis is applicable to patients with genital chlamydia infections. DESIGN: Retrospective cross sectional study. SETTING: Two genitourinary medicine (GUM) clinics in the city of Birmingham and eight adjacent clinics. SUBJECTS: All patients with chlamydia (n = 665) or gonorrhoea (n = 584) attending between 1 October 1995 and 30 September 1996 with a postcode within the Birmingham health district. Controls were 727 patients seen in the same period with no infection. METHODS: Postcodes were used to calculate population prevalence rates per 100,000 aged 15-65 in the 39 wards of the city and to estimate the socioeconomic status using the Super Profile (SP). Ethnic specific rates were also calculated. Data were obtained on gonorrhoea and chlamydia isolation from all the major laboratories of the city over the same time period. RESULTS: GUM clinic attenders accounted for 67.6% and 82.5% of all chlamydia and gonorrhoea isolates reported by the laboratories and that were available for our epidemiological analysis. Both infections were more common in men and in black ethnic groups. However, patients with gonorrhoea only infection were more likely to be of black ethnicity than those with chlamydia only infection (p = 0.0001) and to have different SP distribution (p = 0.0001). On logistic regression age < 20 years, male sex, black ethnicity, and living in neighbourhoods with SP J ("have nots") were predictive of both infections compared with controls. Overall chlamydia and gonorrhoea prevalence rates were 129 and 98.4 per 10(5) respectively. Corresponding rates for whites was 64.7 and 37.2 and for black ethnic groups 1105 and 1183 per 10(5) of each ethnic group. Eight adjacent wards accounted for 41% of the chlamydia and 66.5% of the gonorrhoea. CONCLUSION: In a large urban setting patients attending GUM clinics with chlamydia belong to core population groups with similar, but not identical, sociodemographic characteristics to patients with gonorrhoea infection.
Adolescent↗
Inferior vena cava filters for HIV infected patients with pulmonary embolism and contraindications to anticoagulation.
OBJECTIVES: To describe the mode of presentation, interventions, and outcome of HIV infected patients with pulmonary embolism and a contraindication to anticoagulation, who were treated with a bird's nest filter. METHODS: Retrospective review of case records and imaging department database at UCL Hospitals, London, UK. RESULTS: Three patients had pulmonary embolism and contraindications to anticoagulation. Contraindications were concomitant intracerebral pathology in two patients (one also had bleeding from gastric Kaposi's sarcoma and the other was cognitively impaired with HIV associated dementia complex) and alcohol induced liver disease/binge drinking in the third patient. Anticoagulation was avoided by introducing a bird's nest filter into the inferior vena cava via the common femoral vein. During follow up (7, 8, and 21 months) no complications or recurrent pulmonary emboli occurred. CONCLUSION: The bird's nest inferior vena cava filter has a role in preventing further pulmonary emboli in HIV infected patients with contraindications to anticoagulation.
Adult↗
Dopaminergic therapy in acute encephalitis lethargica.
We describe a patient with an acute illness, with clinical features characteristic of encephalitis lethargica, who responded repeatedly to trials of an apomorphine infusion and subsequently to oral levodopa therapy. This observation implies a direct acute neurotropic effect of the encephalitis on nigral dopaminergic cells. Dopaminergic medication may therefore be helpful in the acute stage of encephalitis lethargica as well as in the delayed post-encephalitic parkinsonian phase of the syndrome.
Acute Disease↗
Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease.
OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p < 0.003). The median SI to the recall antigen PPD was similar in the urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could be because low sensitivity of CT culture failed to diagnose some cases of C trachomatis. However, it may also signify earlier exposure of the patients to chlamydial antigens (for example, C pneumoniae), cross reacting antigens such as heat shock proteins from other microbial species, or a "bystander" activation of chlamydia specific memory T cells trafficking through mucosal lymphoid tissue during urethritis. These results suggest evidence of T cell mediated response to C trachomatis cannot be used as a diagnostic tool.
Adult↗
Serum cysteine levels in HIV infection.
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Adult↗
Isolation and characterisation of T lymphocytes from the urethra of patients with acute urethritis.
OBJECTIVES: To investigate local cellular immune responses in patients with acute urethritis. METHODS: We have established T cell lines from the urethral exudate and examined their phenotype by flow cytometry. As controls, T cell lines were cultured from first pass urine specimens of asymptomatic healthy individuals. RESULTS: Using interleukin 2 (IL-2) alone a T cell line was obtained on only one occasion. Following culture with IL-2, and subsequent expansion by a single stimulation with irradiated allogenic peripheral blood mononuclear cells (PBMC), phytohaemagglutinin (PHA), and IL-2, it was possible to establish T cell lines from 6/6 acute urethritis patients. T cell lines were also obtained from 4/12 controls subjects, but required repetitive rounds of stimulation with mitogen and allogeneic PBMC to produce sufficient cell numbers for analysis. Three of the patient T cell lines were dominated by T cells expressing the gamma delta receptor. CONCLUSION: The gamma delta T cell subset has been associated with immune responses at mucosal surfaces and has the ability to recognise certain bacterial antigens. The gamma delta T cell response may represent an important aspect of the immune response to organisms associated with acute urethritis.
Adult↗
Regression of HIV encephalopathy and basal ganglia signal intensity abnormality at MR imaging in patients with AIDS after the initiation of protease inhibitor therapy.
PURPOSE: To determine whether protease inhibitors cause regression of periventricular white matter signal intensity abnormalities in patients with human immunodeficiency virus (HIV) encephalopathy and whether the changes on magnetic resonance (MR) images correlate with cognitive improvement. MATERIALS AND METHODS: MR images were retrospectively and prospectively analyzed in 16 adult patients with HIV encephalopathy. White matter and basal ganglia signal intensity abnormalities on initial long repetition time (TR) images were compared with those on subsequent long TR images in patients who received and in patients who did not receive protease inhibitors. Clinical correlation was obtained. RESULTS: Of the nine patients receiving protease inhibitors, four showed nearly complete regression, four showed interval stability, and one showed slight progression. Thus, eight patients (89%) demonstrated either stability or improvement in white matter disease, which correlated with cognitive improvement. Of the seven patients not receiving protease inhibitors, six (86%) showed marked progression with a decline in cognitive function and one had no interval change. The difference between the two groups was statistically significant. Of the two patients receiving protease inhibitors who initially had basal ganglia signal intensity abnormalities, one demonstrated resolution and one nearly complete resolution subsequently. CONCLUSION: Although the patient population is small, protease inhibitors may cause regression of periventricular white matter and basal ganglia signal intensity abnormalities in HIV encephalopathy and may have a role in treatment.
AIDS Dementia Complex↗
The clinical load of HIV and AIDS for genitourinary physicians.
We aimed to investigate the extent of genitourinary medicine (GUM) involvement in the clinical management of HIV. A questionnaire survey was conducted on GUM consultants in the UK and the Irish Republic. Clinics were divided into teaching hospitals (THs) undertaking both undergraduate and postgraduate training in GUM, non-teaching training (NTT) centres undertaking specialist training only and non-teaching (NT) centres. Information was obtained on 241 of the 250 consultants on the Royal College of Physician's GUM Committee's records from 117 GUM clinics (including all THs and NTT centres). Four (1 TH and 2 NTT centres) GUM clinics did not see HIV-positive patients, 62 saw 10-99 patients, 18 reported 100-999 and 4 with over 1000 patients attending in 1996. Thirty-five per cent of the 55 THs and NTT centres had over 100 HIV patients. Consultants were involved in the outpatient care of HIV patients in 99.5% and GUM trainees in 85.5% clinics. Overall 47 clinics have their own inpatient HIV beds and 176 consultants (73%) had full (100) or significant (76) input to inpatient HIV management. Only 29% of THs and 12.5% of NTT centres had none or minor input into HIV care. HIV inpatient on-call commitment by the GUM trainees was reported by 64% of training centres. GUM services provide a major input into outpatient and inpatient care of HIV-infected patients in the UK.
Acquired Immunodeficiency Syndrome↗
Thermosensory threshold: a sensitive test of HIV associated peripheral neuropathy?
The purpose of the study was to assess the prevalence of thermosensory abnormalities in patients infected with HIV infection. Using a Thermo Sensory Analyser, we assessed thermosensory threshold for warm sensation (WS) and cold sensation (CS) of the forearm and foot in 40 controls and 75 HIV positive patients, including five patients with clinically evident peripheral neuropathy, three with AIDS-related dementia and 20 with AIDS. We found that thermosensory threshold is a reproducible test. The 95th centile for normal WS of the forearm was 1.4 degrees C above and CS 0.9 degrees C below the baseline temperature of 32 degrees C, and for WS of the foot was 5.3 degrees C and CS 4.4 degrees C respectively. The median WS of the foot for controls was 1.4 (IQR 0.7-2.8) degrees C, for asymptomatic HIV positive patients was 1.9 (1.1-4.2) degrees C, for patients with AIDS was 3.5 (1.6-5.7) degrees C and for those with peripheral neuropathy was 5.4 (1.7-14.9) degrees C (P< 0.05 compared to controls). A higher threshold was also evident for CS in patients with advanced HIV disease. These findings suggest that thermosensory testing is a sensitive tool in detecting early, small nerve fibre disease before the onset of clinically evident peripheral neuropathy.
AIDS Dementia Complex↗
Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients.
An alternative pathway of Trp metabolism involves the conversion of Trp to kynurenine by indoleamine-2,3-dioxygenase, which leads to synthesis of the neurotoxin, quinolinic acid. This study explores the relationship of indoleamine-2,3-dioxygenase activity with stages of HIV infection. Sera from 206 HIV-positive and 72 seronegative subjects were analyzed for Trp and kynurenine. The kynurenine-to-Trp (KT) ratio was calculated. The mean KT ratio of seronegative controls was 36.6 +/- 10.9, and the median ratio was 34.9. The upper limit of the seronegative KT ratio, defined as mean + 2 SD, was 58.4. Patients with HIV infection showed a reciprocal relationship between the KT ratio, the CD4 count, and the stage of the disease. The median KT ratios for asymptomatic and AIDS patients were 50.5 and 117.0, respectively. This study shows that the serum Trp concentration is markedly decreased and that the kynurenine concentration is increased with immune stimulation in HIV infection. This may lead to changes in quinolinic acid and explain some of the pathogenesis of AIDS dementia.
AIDS Dementia Complex↗