Prevalence, distribution and clinical correlates of myocardial fibrosis in systemic lupus erythematosus: a cardiac magnetic resonance study.

OBJECTIVES: To assess the prevalence, distribution and clinical correlates of myocardial fibrosis, as detected by cardiac magnetic resonance (CMR), in systemic lupus erythematosus (SLE). METHODS: Forty-one subjects (average age 39 ± 12 years and 80% female) with SLE underwent CMR imaging at 1.5T, using late gadolinium enhancement (LGE) to quantify the area of myocardial fibrosis in the left ventricle (LV). Subjects also underwent transthoracic echocardiography (TTE) and exercise testing. RESULTS: LGE was detected in 15/41 subjects, 11 with localized LGE (<15% LV mass) and four with extensive LGE (>15% LV mass). The commonest site of LGE was the interventricular septum, with all but one case demonstrating an intramural or inflammatory pattern. The mean age of the >15% LGE group (55 ± 15 years) was significantly higher than the <15% or absent LGE subgroups. Based on both CMR and TTE measurements, subjects with LGE > 15% demonstrated a reduced E/A ratio of 0.9 ± 0.4 relative to the <15% and absent LGE subgroups. LV end-systolic volume (ESVi), end-diastolic volume (EDVi) and maximum exercise capacity were also reduced in the >15% LGE group. CONCLUSIONS: Mid-wall myocardial fibrosis occurs frequently in SLE and is strongly associated with advancing subject age, but not with SLE duration or severity. Extensive LGE may be associated with diastolic dysfunction and impaired exercise capacity, although this may be an epiphenomenon of age. Cardiac magnetic resonance with quantitative assessment of LGE may provide a basis for cardiac risk stratification in SLE.

Inflammatory trigeminal nerve and tract lesions associated with inferior alveolar nerve anaesthesia.

Inferior alveolar nerve blocks are commonly performed for dental anaesthesia. The procedure is generally safe with a low rate of complications. We report a patient with a reproducible, delayed-onset sensory deficit associated with contrast-enhancing lesions in the trigeminal nerve, pons and medulla following inferior alveolar nerve local anaesthesia. We propose that this previously undescribed condition is a form of Type IV hypersensitivity reaction.

A case of HIV-1 slow seroconversion: diagnostic implications.

We report the case of a 30-year-old woman who failed to achieve diagnostic Western blot criteria for HIV-1 infection until 21 months after her initial presentation. This case highlights the importance of suspecting delayed HIV seroconversion in cases with persistently indeterminant Western blots.

Screening and treating pulmonary arterial hypertension in a tertiary hospital-based multidisciplinary clinic: the first 200 patients.

BACKGROUND: Pulmonary arterial hypertension (PAH) is an increasingly recognised serious illness with insidious onset, delayed diagnosis, complex diagnostic algorithms and poor prognosis, but with recently available effective treatments. AIMS: To efficiently diagnose and to offer treatment for PAH, we established a multidisciplinary service in 2005, where patients attend a clinic staffed by specialists in cardiology, respiratory medicine, rheumatology and immunology in a tertiary referral hospital setting. METHODS: We studied the first 200 patients referred. Serology, echocardiography, lung function tests, high-resolution computed tomography, World Health Organisation Class determination and 6-min walk tests and/or right heart catheterisation were performed, as clinically indicated. RESULTS: Of the 200 patients seen, 66 had confirmed pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg) diagnosed on echocardiography ± right heart catheterisation. Of these patients, 58 had catheter-proven PAH (mean pulmonary artery pressure > 25 mmHg with mean wedge pressure < 15 mmHg). Underlying diagnoses for the confirmed PAH patients were idiopathic (32), scleroderma-associated (14), other connective tissue disease (4) and associated with congenital heart disease (8). Patients with confirmed PAH were commenced on PAH-specific therapy--initially bosentan in the majority but sildenafil, and iloprost were occasionally used initially for patient-specific reasons. Median time from when the patient first called the clinic to prescription of therapy was 16 days (interquartile range; 0-31 days). All surviving patients with PAH have attended for regular 6-monthly follow-up visits with a 100% retention rate up to 4 years. CONCLUSION: A multidisciplinary clinic can provide efficient diagnosis and rapid triage to PAH-specific therapy, if appropriate. Retention rates remain high, at follow up.

Tumour necrosis factor (TNF) inhibitor therapy in Susac's syndrome.

Susac's syndrome is the clinical triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss (Susac 1994) [1]. It occurs predominantly in young females and is believed to be an immune-mediated endotheliopathy of small vessels of the brain, retina and cochlea (Neumayer et al. 2009) [2]. Early, aggressive, and sustained immunosuppressive therapy has been recommended for Susac's syndrome and anecdotal evidence has suggested a therapeutic role for monoclonal antibodies (Rennebohm et al. 2008, Lee and Amezcua 2009) [3,4]. We report a case of Susac's syndrome in which the patient improved immediately after tumour necrosis factor (TNF) inhibition with the monoclonal antibody, infliximab.

Loss of correlation between HIV viral load and CD4+ T-cell counts in HIV/HTLV-1 co-infection in treatment naive Mozambican patients.

Seven hundred and four HIV-1/2-positive, antiretroviral therapy (ART) naïve patients were screened for HTLV-1 infection. Antibodies to HTLV-1 were found in 32/704 (4.5%) of the patients. Each co-infected individual was matched with two HIV mono-infected patients according to World Health Organization clinical stage, age +/-5 years and gender. Key clinical and laboratory characteristics were compared between the two groups. Mono-infected and co-infected patients displayed similar clinical characteristics. However, co-infected patients had higher absolute CD4+ T-cell counts (P = 0.001), higher percentage CD4+ T-cell counts (P < 0.001) and higher CD4/CD8 ratios (P < 0.001). Although HIV plasma RNA viral loads were inversely correlated with CD4+ T-cell-counts in mono-infected patients (P < 0.0001), a correlation was not found in co-infected individuals (P = 0.11). Patients with untreated HIV and HTLV-1 co-infection show a dissociation between immunological and HIV virological markers. Current recommendations for initiating ART and chemoprophylaxis against opportunistic infections in resource-poor settings rely on more readily available CD4+ T-cell counts without viral load parameters. These guidelines are not appropriate for co-infected individuals in whom high CD4+ T-cell counts persist despite high HIV viral load states. Thus, for co-infected patients, even in resource-poor settings, HIV viral loads are likely to contribute information crucial for the appropriate timing of ART introduction.

The uptake of HIV post-exposure prophylaxis within a sexual assault setting in Sydney, Australia.

Our aim was to compare the assault characteristics of victims presenting to a sexual assault service who were prescribed HIV post-exposure prophylaxis (HIV PEP) with those not prescribed HIV PEP. A retrospective review was carried out of the medical records of victims who were seen over a 12-month period in 1999/2000.HIV PEP may have been potentially appropriate for 117 victims, of whom nine (7.7%) were prescribed PEP (eight women, one man). There was a trend for prescription of PEP to depend on the type of assault, with those suffering anal penetration most likely to be prescribed PEP, followed by those with vaginal, and then oral penetration (P = 0.08). Those who gave a history of oral or vaginal mucosal contact with ejaculate were more likely to receive PEP compared with those in whom ejaculation occurred at a non-mucosal site (P = 0.03). Most prescribed PEP regimens involved three antiretroviral drugs. In this study, HIV PEP, when prescribed, was in accord with existing guidelines. Future studies should aim to better document HIV seroconversions in victims of sexual assault and HIV seroprevalence in assailants.

Clinical features and predictors of survival of AIDS-related non-Hodgkin's lymphoma in a population-based case series in Sydney, Australia.

OBJECTIVES: To analyse clinical features and predictors of survival for AIDS-related non-Hodgkin's lymphoma (NHL) in the era of highly active antiretroviral therapy (HAART), compared to earlier in the HIV epidemic. METHODS: All AIDS-NHL cases diagnosed at three inner Sydney hospitals caring for people with AIDS during 1985-2001 were identified through medical record searches. Demographic, clinical, immunological and histopathological information was recorded. Year of NHL diagnosis was grouped into three periods, corresponding to whether monotherapy (1985-1991), dual therapy (1992-1995) or HAART (1996-2001) was the main treatment for HIV infection. Statistical comparisons were made between the pre-HAART and post-HAART eras. RESULTS: Three hundred cases of AIDS-NHL were identified. Divergent trends were identified for systemic and primary central nervous system (CNS) NHL. For systemic NHL, the CD4 count at NHL diagnosis increased markedly to 208 cells/microL in the post-HAART era (P=0.014) and there was a trend towards presentation as the first AIDS-defining illness (69%, P=0.053), and as earlier stage NHL disease (42%, P=0.048). Median survival time increased from 4.2 months in 1985-1991 to 19 months in the post-HAART era (P<0.001). In a multivariate model, predictors of poor survival from systemic NHL included: NHL diagnosis after another AIDS-defining illness (P<0.001), stage 4 NHL (P<0.001), presentation at extra lymphatic sites (P=0.001), and nonreceipt of chemotherapy (P=0.002). After adjusting for the factors, those diagnosed in the era of HAART had a significant 56% reduction in rate of death (P<0.001). In contrast, for CNS NHL, clinical features were little changed and survival did not improve in the era of HAART. CONCLUSIONS: Systemic NHL is presenting earlier in the course of HIV disease, and at a less advanced NHL stage. There has been a marked improvement in survival in the era of HAART even after adjustment for other prognostic variables. In contrast, primary CNS NHL remains a disease which presents late in the course of HIV infection and is associated with a very poor prognosis.

Calculating energy requirements for men with HIV/AIDS in the era of highly active antiretroviral therapy.

OBJECTIVES: 1. To determine if resting energy expenditure (REE) adjusted for body composition is elevated in HIV-positive males when compared with healthy controls in the era of highly active antiretroviral therapy. 2. To examine the accuracy of prediction equations for estimating REE in people with HIV. 3. To determine if REE adjusting for body composition is significantly different between those HIV-positive subjects reporting lipodystrophy (LD) or weight loss (>or=5%) and those who are weight stable when compared to controls. DESIGN: Cross-sectional study. SETTING: Tertiary referral hospital HIV unit and an outpatient clinic specializing in HIV care. SUBJECTS: HIV-positive males (n=70) and healthy male controls (n=16). METHODS: REE was measured using indirect calorimetry. Body composition was assessed using bioelectrical impedance analysis. RESULTS: 1. REE when adjusted for fat-free mass and fat mass using the general linear model (analysis of covariance) was greater in HIV-positive subjects than controls (7258+/-810 kJ, n=70 vs 6615+/-695 kJ, n=16, P<0.05). 2. The Harris and Benedict, Schofield, Cunningham and the two equations previously published by Melchior and colleagues in HIV-positive subjects all gave an estimate of REE significantly different from the measured REE in the HIV-positive subjects, therefore a new prediction equation was developed. The inability of the published equations to predict REE in the different HIV-positive subgroups reflected the heterogeneity in body composition. 3. REE adjusted for fat-free and fat mass was significantly greater in the both the HIV patients who were weight stable and those with lipodystrophy compared with the healthy controls. CONCLUSION: REE is significantly higher in HIV-positive males when compared with healthy controls. Body composition abnormalities common in HIV render the use of standard prediction equations for estimating REE invalid. When measuring REE in HIV-positive males adjustment steps should include fat-free and fat mass.

A comparison of megestrol acetate, nandrolone decanoate and dietary counselling for HIV associated weight loss.

This randomized, prospective study compared three treatments, nandrolone decanoate (ND), megestrol acetate (MA) or dietary counselling, for managing human immunodeficiency syndrome (HIV) associated weight loss. It was centred on a Tertiary referral hospital, Sydney, Australia. Fifteen patients were randomized to receive ND (100 mg/fortnight), or MA (400 mg/day) or dietary counselling for 12 weeks. Those patients randomized to dietary counselling were further randomized to receive nandrolone or megestrol after completing the dietary counselling arm. Weight, fat free mass (FFM), percentage body fat mass (FM), dietary intake and appetite were assessed before commencing and at the completion of each treatment arm. Weight increased significantly in all treatment arms (dietary counselling 1.13 kg +/- 0.36, nandrolone 4.01 kg +/- 1.68, megestrol 10.20 kg +/- 4.51, p < 0.05 paired t-test). FFM increased significantly in patients receiving ND (3.54 +/- 1.98 kg, p=0.001) and those receiving MA (2.76 +/- 0.55 kg, p=0.002), whereas the change in those receiving dietary counselling alone was not significant. Percentage body fat mass increased significantly only in those receiving MA (7.77 +/- 4.85%, p=0.049). The change in weight and percentage body fat mass was significantly greater in those receiving MA than the other two treatment arms. The increase in FFM was significantly greater in both the nandrolone and megestrol arms than the dietary counselling arm. It was concluded that ND and MA both resulted in an increase in FFM greater than dietary counselling alone. Megestrol produced a significantly greater increase in weight, percentage fat mass, intake and appetite than did the other two treatment arms, suggesting it may be the preferred agent, particularly in a palliative care setting in which weight, appetite and intake increase are desirable without regard to the composition of the body. The long-term use of these agents in people with HIV should be reviewed in the context of improved survival on highly active antiretroviral therapy regimens.

Dietary intake, serum lipids, insulin resistance and body composition in the era of highly active antiretroviral therapy 'Diet FRS Study'.

OBJECTIVES: To investigate (i) differences in dietary fat and energy intake between those reporting and those not reporting fat redistribution syndrome (FRS), and (ii) the relationship between dietary fat, total energy intake, serum biochemistry and the clinical characteristics of the syndrome. DESIGN: A cross-sectional study. SETTING: Outpatient service of a tertiary referral hospital, Sydney, Australia. PATIENTS AND METHODS: Dietary intake, serum lipids and insulin resistance and body composition (fat-free mass, fat mass, waist-to-hip ratio; WHR) were determined in 100 HIV-positive patients whose FRS status was classified on the basis of self-report of body composition changes, verified by clinical examination. RESULTS: There was no significant difference in total or saturated dietary fat intake when grouped by FRS status. There was no significant correlation between dietary saturated or total fat intake and the serum or body composition parameters measured. Total energy intake was higher in those patients reporting FRS (14575 versus 12283 kJ, P = 0.037) after adjustment for age, smoking and exercise status. CONCLUSION: There appears to be no relationship between either dietary saturated or total fat intake and the serum or body composition parameters characteristic of FRS; however, the total energy intake was significantly higher in those with FRS. The nature of the relationship between total energy intake and FRS (cause or effect) warrants further investigation.

B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS.

OBJECTIVES: To identify risk factors for non-Hodgkin's lymphoma (NHL) in people with HIV infection. DESIGN AND SETTING: Case-control study in Sydney, Australia. PARTICIPANTS AND METHODS: Two hundred and nineteen patients with AIDS-related NHL were compared with 219 HIV-infected controls without NHL, matched for CD4 positive cell count and date of specimen collection. Data on demographic, infectious, treatment-related and immunological factors were abstracted by medical record review. The association between demographic factors, sexually transmissible diseases, HIV-related opportunistic infections, anti-viral therapy, duration of immune deficiency and indices of immune stimulation and risk of NHL were derived for these groups. RESULTS: In a multivariate model, there were two independent groups of predictors of NHL risk. The first was duration of immunodeficiency, as measured by longer time since seroconversion (P for trend 0.008), and lower CD4 positive cell count 1 year prior to the time of NHL diagnosis (P for trend 0.009). The second predictor was B-cell stimulation, as indicated by higher serum globulin (a surrogate marker for serum immunoglobulin, P for trend 0.044) and HIV p24 antigenaemia [odds ratio (OR) for p24 positivity, 1.82; 95% confidence interval (CI), 1.15-2.88]. Indices of B-cell stimulation preceded the diagnosis of NHL by several years. Factors not related to NHL risk included clinical indices of Epstein-Barr virus infection and receipt of individual nucleoside analogue antiretroviral agents. Combination therapy with these agents was associated with a non-significant reduction in NHL risk (OR, 0.68; 95% CI, 0.39-1.18). CONCLUSIONS: Markers of long-standing immune deficiency and B-cell stimulation were associated with an increased risk of developing NHL. Unless the strongest risk factor for NHL, immune deficiency, can be reversed, NHL is likely to become proportionately more important as a cause of morbidity and mortality in people with HIV infection.

Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort.

BACKGROUND AND METHODS: The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type 1 (HIV-1) with a deletion in the region in which the nef gene and the long terminal repeat overlap. Two recipients have died since 1994, at 77 and 83 years of age, of causes unrelated to HIV infection; one other recipient, who had systemic lupus erythematosus, died in 1987 at 22 years of age of causes possibly related to HIV. We present longitudinal immunologic and virologic data on the six surviving members and one deceased member of this cohort through September 30, 1998. RESULTS: The five surviving recipients remain asymptomatic 14 to 18 years after HIV-1 infection without any antiretroviral therapy; however, the donor commenced therapy in February 1999. In three recipients plasma concentrations of HIV-1 RNA are undetectable (<200 copies per milliliter), and in two of these three the CD4 lymphocyte counts have declined by 9 and 30 cells per cubic millimeter per year (P=0.3 and P=0.5, respectively). The donor and two other recipients have median plasma concentrations of HIV-1 RNA of 645 to 2850 copies per milliliter; the concentration has increased in the donor (P<0.001). The CD4 lymphocyte counts in these three cohort members have declined by 16 to 73 cells per cubic millimeter per year (P<0.001). In the recipient who died after 12 years of infection, the median plasma concentration of HIV-1 RNA was 1400 copies per milliliter, with a decline in CD4 lymphocyte counts of 17 cells per cubic millimeter per year (P=0.2). CONCLUSIONS: After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV-1 RNA. The CD4 lymphocyte counts appear to be stable in the three subjects in whom plasma HIV-1 RNA remains undetectable.

Atopy, anergic status, and cytokine expression in HIV-infected subjects.

BACKGROUND: In HIV infection T-cell dysfunction resulting in anergy and hypersensitivity reactions precedes T-cell depletion. A shift in the cytokine profile from a type 1 to a type 2 response has been postulated. OBJECTIVE: We sought to examine the cytokine expression patterns in HIV infection and the relationship to allergy, stage of HIV disease, and other laboratory parameters. METHODS: A cross-sectional analysis of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p35, IL-13, and IFN-gamma mRNA expression in PBMCs by noncompetitive dot-blot PCR was performed on blood obtained from 18 HIV-infected subjects. Delayed-type hypersensitivity multitests to detect anergy, skin prick testing and in vitro assay for specific IgE antibodies, assay for total IgE, and enumeration of eosinophils, CD4(+), and CD8(+) T cells were also performed on all subjects. RESULTS: We found evidence of a decline in type 1 cytokines (IL-2, IL-12p35, and IFN-gamma) associated with AIDS, CD4(+) T cells less than 200/microL, anergy, and atopy, although this only reached statistical significance in anergy. There was no associated significant alteration in type 2 cytokines. CONCLUSIONS: This is the first report of an association between low constitutive in vivo expression of IL-12 mRNA and anergy, which supports earlier data from in vitro stimulation studies. The presence of atopy was associated with a more global reduction in cytokine expression. Because the decline in type 1 cytokines was not accompanied by a similar decline in type 2 cytokines, this does suggest a shift in the type 1/type 2 balance.

Outpatient continuous intravenous interleukin-2 or subcutaneous, polyethylene glycol-modified interleukin-2 in human immunodeficiency virus-infected patients: a randomized, controlled, multicenter study. Australian IL-2 Study Group.

The safety and activity of outpatient-based continuous intravenous interleukin-2 (CIV IL-2) or a slow-release, polyethylene glycol (PEG)-modified IL-2 were studied in human immunodeficiency virus (HIV)-infected persons with CD4 cell counts between 200 and 500/mm3. One hundred fifteen patients were randomized to antiretroviral therapy plus cyclical CIV IL-2 (n = 27), subcutaneous PEG IL-2 (n = 58), or no IL-2 (n = 30). Toxicity withdrawal rates were low (4% for CIV IL-2 and 7% for PEG IL-2). There were median CD4 cell count increases of 359 and 44 cells/mm3 and a decline of 46 cells/mm3 in the 3 groups, respectively, over 1 year (P < .0001 for each intergroup comparison). CD4 cell count increases were greatest in those with lower HIV RNA load. Delayed-type hypersensitivity scores increased and HLA-DR expression on CD8 cells decreased significantly with IL-2 therapy. HIV RNA levels were unaffected. IL-2 therapy may expand the existing immune repertoire but not immediately reconstitute lost immune function.

Relapsing polychondritis presenting with recurrent venous thrombosis in association with anticardiolipin antibody.

We describe a case of relapsing polychondritis with recurrent venous thrombosis associated with detectable anticardiolipin antibody. This association has not been previously reported, although venous and arterial thrombosis has been recognized in association with relapsing polychondritis.