Search

Highly active antiretroviral therapy (HAART)-induced lipoatrophy is characterized by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and recombinant methionyl human leptin (metreleptin) administration has beneficial effects in human immunodeficiency virus (HIV)-infected lipoatrophic patients. This proof-of-concept study aimed at evaluating whether the combination of metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected patients on HAART. Nine HIV-positive men with at least 6 months of HAART exposure, clinical evidence of lipoatrophy, and low leptin concentrations (≤4 ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo, metreleptin reduced fasting serum insulin concentration, increased adiponectin concentration, reduced the homeostasis model assessment index of insulin resistance, and attenuated postprandial glycemia in response to a mixed meal (all P ≤ .02), but did not affect trunk and peripheral fat mass. HIV control was not affected, and no major adverse effects were observed. Metreleptin administration in HIV-positive, leptin-deficient patients with lipoatrophy treated with pioglitazone improves postprandial glycemia and insulin sensitivity. Results from this pilot study should be confirmed in larger clinical trials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Leptin is an adipocyte secreted hormone and an important regulator of neuroendocrine, metabolic, and immune function. Both r-metHuLeptin and IGF1 administration result in reduced central adipose tissue in subjects with highly active antiretroviral therapy-induced metabolic syndrome (HAART-MS) but whether the effects of leptin are mediated through increasing IGF levels remains unknown., Methods: To assess whether r-metHuLeptin improves the HAART-MS by regulating circulating IGF and IGFBPs, we first conducted a cross-sectional study of 118 men and women with HIV infection and >6 months of exposure to antiretroviral medications to examine any association between circulating IGF1 and leptin levels. We also performed a randomized, double-blinded, placebo-controlled, crossover trial of recombinant human leptin (r-metHuLeptin) administration to seven HIV positive men with lipoatrophy and leptin deficiency (leptin <3 ng/ml) related to antiretroviral medication use., Results: In the observational study, leptin levels were inversely associated with circulating IGF1 levels after adjusting for age and gender (r=0.27 P=0.002), but this inverse association became non-significant after adjustment for % body fat and exercise. In the interventional leptin study, leptin levels increased significantly during r-metHuLeptin treatment (from 1.34+/-0.20 ng/ml at baseline to 17+/-5.05 ng/ml after 8 weeks P=0.046) and metabolic parameters improved including reduced fasting insulin levels and reduced homeostasis model assessment-insulin resistance (HOMA-IR). Despite the increase in circulating leptin levels, there was no change in IGF1, IGF2, free IGF1, or IGF-binding proteins during the 2-month treatment period., Conclusion: The effects of r-metHuLeptin in patients with HAART-MS are not mediated through increasing IGF or IGFBP levels.

To our knowledge, an association between human immunodeficiency virus infection and pseudo-Cushing's syndrome has not previously been described. We describe four HIV-infected patients with pseudo-Cushing's syndrome, characterized by striking dorsocervical and submandibular fat accumulation and central obesity. In each case, cortisol levels were either normal or suppressed adequately with administration of dexamethasone, excluding the diagnosis of true Cushing's syndrome. Immune function and weight improved significantly preceding the development of pseudo-Cushing's syndrome. Three of the four patients were taking a common protease inhibitor at the onset of symptoms, and the fourth reported the exacerbation of his symptoms with the addition of a protease inhibitor. The observed characteristic pattern of fat deposition may be attributable to a specific effect of new antiretroviral therapies or may relate to recovery independent of medication usage. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. Further research into the mechanisms of this novel phenomenon is needed.

We describe five cases of parasitic sinusitis and otitis in patients infected with human immunodeficiency virus (HIV) and review 14 reported cases. The pathogens identified in our group of patients included agents such as Microsporidium, Cryptosporidium, and Acanthamoeba species. The clinical features common to these patients included a long history of HIV seropositivity associated with advanced immunosuppression and multiple opportunistic infections as well as long-standing local symptoms refractory to multiple courses of antibacterial agents. Symptoms often included fever and chills in addition to local tenderness and discharge. Invasive diagnostic procedures were necessary to obtain the final diagnosis and to initiate appropriate therapy. Although most patients responded at least partially to specific therapy, relapses and recurrences were frequent in patients who did not receive long-term suppressive therapy. The general outcome for HIV-infected patients with parasitic sinusitis and otitis was poor; however, deaths were generally associated with other complications of the underlying HIV infection.

Background: The acquired immunodeficiency syndrome (AIDS) is frequently complicated by malnutrition that may require parenteral nutritional support. In a non-AIDS population with long-term indwelling central venous catheters, low-dose warfarin therapy has been shown to prevent venous thrombosis. The purpose of this study was to determine the incidence of symptomatic central venous thrombosis in AIDS patients receiving home parenteral nutrition. The incidence of thrombosis on low-dose warfarin was compared with no prophylactic therapy., Methods: A retrospective review of 47 malnourished AIDS patients started on home parental nutrition was performed. None of the patients had a prior history of venous thrombosis. During this period, 9 of 47 patients were treated with low-dose warfarin therapy. The incidence of clinical and radiologic venous thrombosis was compared in these two groups., Results: Forty-seven patients were treated with parenteral nutrition for 296 patients-months. The rate of central venous thrombosis in patients receiving warfarin (0.016 thromboses per patient-month) was no different from those patients on no prophylactic therapy (0.009 thromboses per patient-month). The most common abnormality in coagulation observed in the entire group during follow-up was thrombocytopenia occurring in 66% of patients. Sixty percent of patients received medications that could interfere with platelet function., Conclusions: We conclude that routine thrombosis prophylaxis with low-dose warfarin may not be justified in malnourished AIDS patients receiving home parenteral nutrition. Prospective clinical trials are needed to determine the risks and benefits of prophylactic warfarin therapy in this group of patients.

Background: Albumin has a role in the complicated process of platelet aggregation. Although it is known that quantitative changes in plasma albumin alter platelet aggregation, less is known about the interaction between qualitative changes in plasma albumin and platelets. One common qualitative change in plasma albumin is nonenzymatic glycosylation, which occurs during states of prolonged hyperglycemia., Methods: Albumin was selectively removed from normal plasma by means of an affinity column. Glycosylated albumin was added to this albumin-poor plasma, and it was used to study platelet aggregation induced by low concentrations of arachidonic acid. Platelet aggregation was determined by light transmittance., Results: As the concentration of glucose in which albumin was incubated was increased, there was progressive augmentation of platelet aggregation. At a plasma glucose of 150 mg/dL, average light transmittance was 9.4%, and at 200 mg/dL, it was 24.6%. These values were significantly different at a p value < .01. At glucose levels of 300 mg/dL and 400 mg/dL, mean light transmittance was 40.6% and 74.4%, respectively, and these values were significantly different with p values of < .01., Conclusions: Platelet aggregation in response to a relatively low concentration of arachidonic acid is enhanced in the presence of albumin that has been incubated in a medium containing levels of glucose that are higher than would be seen in normal patients but are consistent with those seen in diabetics with less than optimal control. This augmentation of platelet aggregation is statistically significant.

We report the association of subcutaneous emphysema with the use of a suprapubic bladder catheter. Review of the literature has revealed no prior reports of this complication. We have reviewed the literature on causes of tissue emphysema.

The majority of patients with cancer become anemic during the course of their disease. This anemia appears to be due largely to a blunted erythropoietin (Epo) response and an impaired ability of the bone marrow to respond to endogenous Epo. Both are exacerbated by chemotherapy and radiation therapy. Recombinant human erythropoietin (rhEpo) ameliorates the anemia associated with malignancy. However, we do not yet know whether rhEpo will decrease the need for homologous blood transfusions and improve the quality of life of cancer patients. While rhEpo will greatly alter the treatment of anemia in the 1990s, its precise role in the treatment of oncology patients is still being elucidated.