Publications

OBJECTIVE

To determine the relationship of HIV infection, demographic, and cardiovascular disease (CVD) risk factors with mortality in the recent highly active antiretroviral therapy era.

METHODS

Vital status was ascertained from 2004 to 2007 in 922 HIV infected and 280 controls in the Study of Fat Redistribution and Metabolic Change in HIV infection; 469 HIV infected were included in analysis comparing HIV with similar age controls. Multivariable exponential survival regression (adjusting for demographic and CVD factors) estimated hazard ratios (HRs) for death.

RESULTS

After 5 years of follow-up, the overall adjusted mortality HR was 3.4 [95% confidence interval (CI): 1.35-8.5]; HR was 6.3 among HIV infected with CD4 < 200 (95% CI: 2.2-18.2), 4.3 with CD4 200-350 (95% CI: 1.14-16.0), and 2.3 with CD4 > 350 (95% CI: 0.78-6.9). Among HIV infected, current smoking (HR = 2.73 vs. never smokers, 95% CI: 1.64-4.5) and older age (HR = 1.61 per decade, 95% CI: 1.27-2.1) were independent risk factors for death; higher baseline CD4 count was associated with lower risk (HR = 0.65 per CD4 doubling, 95% CI: 0.58-0.73).

CONCLUSIONS

HIV infection was associated with a 3-fold mortality risk compared with controls after adjustment for demographic and CVD risk factors. In addition to low baseline CD4 count, older age and current smoking were strong and independent predictors of mortality in a US cohort of HIV-infected participants in clinical care.

Constitutive activity of the extracellular calcium-sensing receptor (CaSR) has been studied in kindreds with the human disorder autosomal dominant hypocalcemia (ADH) and in an animal model called the Nuf mouse. These families generally showed reduced parathyroid hormone (PTH) secretion and excessive renal calcium (Ca(2+)) excretion. Soft tissues calcifications in the kidney and basal ganglia are frequent (10-50% of ADH cases), and there is a single report of skeletal abnormalities in a family resulting in short stature and premature osteoarthritis. In the latter, a causative mechanism could not be determined. The phenotype of the Nuf mouse is one of ectopic calcifications and cataracts in addition to biochemical abnormalities (low serum Ca(2+) and high serum phosphate concentrations). To better understand the role of CaSRs in the control of osteoblastic function, we generated a transgenic mouse model with constitutively active CaSRs in mature osteoblasts. An analysis of the skeletal phenotype of that mouse indicates that strong signaling by CaSRs in this cell lineage induces alterations in the bone homeostasis reflected in mild osteopenia in male and female mice during growth and in adulthood. These studies indicate that this approach can be readily adapted to assess CaSR actions in other cell systems.

With improved survival afforded by highly active antiretroviral therapy (HAART), CKD has emerged as one of the primary comorbid conditions affecting HIV-infected individuals. Although CKD in HIV-infected individuals is classically thought of as a consequence of advanced HIV infection such as in the case of HIV-associated nephropathy, several factors likely contribute to the development CKD in HIV infection. These factors include genetic predisposition, age-related decline in kidney function, HAART-related metabolic changes, exposure to multiple nephrotoxic medications, and concurrent conditions such as hepatitis C or illicit drug use. Similar to the general population, proteinuria and impaired kidney function are associated with faster progression to acquired immune deficiency syndrome and death. Given the prevalence and impact of kidney disease on the course of HIV infection and its management, current guidelines recommend screening all HIV-infected individuals for kidney disease. This review focuses on the current guidelines for kidney disease screening and discusses traditional as well as promising strategies for detecting CKD in this vulnerable population.

OBJECTIVE

To assess the effect of mycophenolate mofetil compared with intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus nephritis.

METHODS

Patients with active lupus nephritis (renal biopsy class III, IV, or V) were recruited for the study (n = 370) and treated with mycophenolate mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5-1.0 gm/m(2)/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were determined using measures of whole body disease activity, including the British Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic variables.

RESULTS

Both treatments were effective on whole body disease activity in the systems examined, as indicated by changes in the classic BILAG index. With either treatment, remission was induced, notably in the mucocutaneous, musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares were rare, as measured by the SELENA-SLEDAI. Levels of complement C3, C4, and CH50 and titers of anti-double-stranded DNA antibodies were normalized after treatment with either mycophenolate mofetil or intravenous cyclophosphamide.

CONCLUSION

In addition to the efficacy of both treatments on the renal system, this analysis showed that remission could also be induced in other systems. There was no clear difference in efficacy between mycophenolate mofetil and intravenous cyclophosphamide in ameliorating either the renal or nonrenal manifestations. Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide for the treatment of renal and nonrenal disease manifestations in patients with biopsy-proven lupus nephritis.

A new era in the treatment of systemic lupus erythematosus (SLE) may be dawning. Twelve years after the first approval of biologic therapy for patients with rheumatoid arthritis, the positive results of two large trials of a novel biologic therapy for SLE have raised hopes that a new approach to treatment may be at hand. This encouraging news follows several disappointments in trials of other biologic therapies and provides a timely moment to reflect on where we stand, what we have learned, and what may lie ahead.

Normal anatomic variation in the amount of fat within the petrous temporal bone of dogs can result in a magnetic resonance (MR) imaging pseudolesion. Focal hyperintense areas in the region of the hippocampus on T1-weighted, T1-weighted, and fluid-attenuated inversion recovery imaging sequences were noted in a dog being imaged for seizure activity. Further investigation of this region, aided by the use of cadaveric specimens, led to the identification of normal anatomic variability in the amount of fat in the substantia spongiosa of the petrous temporal bone. The presence of normal adipose tissue was confirmed histopathologically. Fat suppression MR imaging sequences can be used to differentiate whether hyperintensity ventral to the hippocampus is a result of a pathologic process, or fat in the substantia spongiosa of the petrous temporal bone.

A 10-month-old dog was presented with clinical signs of fever, lethargy, inappetence, and cardiac arrhythmias. Computed tomography scan and cerebrospinal fluid analysis supported the diagnosis of steroid-responsive meningitis-arteritis. Echocardiography, electrocardiogram, and elevated serum troponin I supported a diagnosis of myocarditis. The arrhythmias resolved during treatment of the primary neurological disease, and they were considered as secondary to the meningitis.