Is resistin a link between highly active antiretroviral therapy and fat redistribution in HIV-infected children?

OBJECTIVES: To assess the features of fat redistribution, detected by clinical and ultrasound (US) methods, and the presence of metabolic disorders in HIV-infected children undergoing antiretroviral therapy. To evaluate if serum levels of resistin, a hormone produced only by visceral adipose tissue, are a marker of fat redistribution in these patients. DESIGN AND METHODS: Forty-five consecutive symptomatic HIV-infected children were considered for inclusion in the study. Patients were enrolled if treated for at least 6 months with antiretroviral therapy with or without protease inhibitor (PI) and if compliant to the study protocol. Patients were evaluated for: anthropometric measures, fat redistribution by clinical and US methods, serum lipids, parameters of insulin resistance by homeostasis model assessment for insulin resistance, serum resistin levels by an enzyme-linked immunosorbent assay. RESULTS: Eighteen children fulfilled the inclusion criteria and were enrolled in the study. Twelve (66%) children had clinical and/or US evidence of fat redistribution; 9 (75%) of them were on PI therapy; only 3 of 6 children without fat redistribution were on PI therapy (p<0.05). Serum lipids and insulin resistance parameters did not differ between children with or without fat redistribution. There was a highly significant linear correlation between visceral fat detected by US and circulating resistin levels (r=0.87; p<0.0001). CONCLUSIONS: Fat redistribution occurred in most HIV-infected children undergoing PI therapy. Because serum resistin levels reflect the amount of visceral fat, they could be considered a sensitive marker of fat redistribution in HIV-infected children.

Impact of prebiotics on human health.

It is becoming clear that intestinal microflora plays an important role in the development of local and systemic immune response. Nutritional ingredients have been added to infant formula in an attempt to make its composition similar to that of human milk. The effects of these modifications have been observed in the composition of intestinal microflora. Prebiotics are non-digestible foods able to selectively stimulate the growth/activity of a limited number of colonic bacteria. A mixture of galacto-oligosaccharides and fructo-oligosaccharides (GOS/FOS) induces an increase in Bifidobacteria, similar to that of breast-fed infants. What is less clear is whether the modifications of intestinal microflora obtained by functional foods are associated with clinically measurable effects. Preliminary indirect data suggest that increasing the load of Bifidobacteria and Lactobacilli may protect from infections and allergies and this effect may persists beyond infancy. The emerging concept is that early nutritional intervention may be effective in modifying the intestinal microflora composition in a phase in which microbiological imprinting may drive immunological imprinting thereby producing clinical effects. Further investigations and well designed randomised clinical trials are needed to demonstrate the potential beneficial effects and to exclude the potential side effects.

Prolonged response to cyclosporin-A in hypoplastic refractory anemia and correlation with in vitro studies.

BACKGROUND AND OBJECTIVE: Lymphocyte abnormalities in myelodysplastic syndromes (MDS) have been widely described, but the role of the immune system in the pathogenesis of these clonal disorders remains controversial. An active role of lymphocytes in suppressing normal hematopoiesis may be implicated in MDS with hypoplastic marrow. We have studied in vitro and in vivo activity of cyclosporin-A (CSA) on hematopoiesis in patients affected by hypoplastic MDS without blast excess. DESIGN AND METHODS: Nine consecutive patients with hypoplastic refractory anemia (RA), followed up in our out-patient unit, were treated with CSA at daily doses of 1-3 mg/kg for at least three months. Low dose steroids or danazol were transiently added in 7/9 patients. Differences between pre- and post-treatment parameters were studied by the Student's t-test. In vitro effect of CSA on circulating hematopoietic progenitors was studied by the methylcellulose colony assay. RESULTS: Before treatment, fewer circulating hematopoietic progenitors were found in all patients as compared to normal subjects. The number of CD34+ cells was about halved, while circulating erythroid and myeloid colony-forming cells (CFC) were reduced to one-fifth. After a mean period of 22 months of CSA treatment (median: 14.5 months), hemoglobin was significantly and persistently increased in two patients, platelets in one, platelets and hemoglobin in two. Two patients showed transient responses, one patient did not tolerate the treatment and one patient is close to a significant response. At in vitro CSA concentrations similar to those achieved in vivo after oral administration the drug significantly increased cell colony growth in hypoplastic RA. This test correctly predicted a positive clinical response to CSA in 3/5 cases and treatment failure in 4/4 cases. INTERPRETATION AND CONCLUSIONS: About one half of hypoplastic RA patients benefited from CSA treatment. A larger study could verify whether in vitro culture of hematopoietic progenitors in the presence of CSA can predict the clinical response and whether this treatment could prolong patients' survival.

Dermochondral corneal dystrophy (of François).

Dermochondral corneal dystrophy (of François) has been reported rarely in the literature. It consists of a triad of findings characterised by the development of skin nodules, acquired deformities of the extremities, and a corneal dystrophy. The corneal dystrophy is central and superficial with whitish subepithelial opacities. We present two brothers who display previously unreported ocular findings. Specifically, they developed confluent opacification of their central corneas with anterior stromal involvement, and peculiar anterior cortical cataracts. These findings should be added to the spectrum of findings seen in this rare disorder.

Effect of deliberate blood transfusions in cadaveric kidney allografts at a single center.

The effectiveness of deliberate pre-transplant blood transfusions was compared in randomly transfused and nontransfused patients who acted as controls at a single transplant center. The patients in the pre-transplant transfusion group who had never been transfused had better graft survival than all other groups. Next, were those patients who had previous random transfusions and were then placed in the deliberately transfused group. Those who had received random blood transfusions but were not in the protocol and those patients who never had transfusions did the poorest. Those patients never transfused previously who received the scheduled transfusions had far lower levels of antibodies than those who had had previous transfusions and those with previous transfusions who were then entered into the prospective transfusion protocol. The patients who had B cold cytotoxic antibodies had the highest graft survival rates. Timing was important, with the group receiving the last transfusions 3 to 6 weeks before transplantation doing significantly better than any other group. Histocompatibility locus-A and B antigen distribution among the groups did not bias the data.

Posttransplant serum analysis in human kidney allografts.

Monitoring of 25 first cadaver transplant recipients was carried out weekly after transplantation. A total of 441 sera were tested from these patients against B and T lymphocytes at 4 degrees C and 37 degrees C for development of cytotoxic antibodies. Thirteen of the 25 patients (52%) developed B-cold antibodies as their first antibodies and all had functioning kidneys. Five of the patients developed B-warm antibodies initially, and all 5 rejected their transplants within 24 days. Of the seven patients who did not develop antibodies, 3 rejected their kidneys within 72 days. We conclude that it is important to distinguish between two types of antibodies to B lymphocytes--those reactive in the cold and those reactive in the warm--since they have opposite effects. Of the 17 successful grafts, 13 first developed B-cold cytotoxins.