Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects.

To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat-derived factor retinol-binding protein-4 (RBP-4) in HIV-infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Fourteen HIV-positive, HAART-naïve subjects were compared with 10 HIV-negative healthy controls and reassessed after a 1-year treatment with HAART. Plasma visfatin and RBP-4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X-ray absorptiometry (DXA). Homeostasis model assessment (HOMA-IR) was assessed using insulin and glucose levels. Visfatin and RBP-4 levels in HIV-positive subjects were comparable with those of HIV-negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6.9-fold and 7.1-fold increase of visfatin and RBP-4 levels (+54.0 +/- 9.7 ng mL(-1), P < 0.0001 and +95.3 +/- 31.7 ng mL(-1), P < 0.01), respectively. Leptin (-2.7 +/- 1.6 ng mL(-1), P = 0.054) was unchanged and adiponectin (-2.8 +/- 0.7 microg mL(-1), P < 0.01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP-4 (r = 0.78, P = 0.001), fat-free mass (FFM, r = 0.75, P < 0.05) and change of HOMA-IR (r = 0.64, P < 0.05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Treatment with HAART induced a pronounced increase of plasma visfatin and RBP-4 as well as a decrease of adiponectin in HIV-infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.

Anaplastic squamous cell carcinoma (SCC) in a patient with chronic cutaneous graft-versus-host disease (GVHD).

We describe an allogeneic bone marrow (BM) recipient who developed aggressive, metastasizing squamous cell cancer (SCC) of the skin, and discuss possible risk factors in the development of this secondary solid tumor. The patient had been treated with cyclosporine (CsA), methyl-prednisolone and thalidomide for 3 years because of extensive de novo chronic cutaneous GVHD occurring 1 year after BMT. Ten years after BMT a locally invasive and metastasizing SCC occurred on the patient's neck, and diagnosis was confirmed by H&E histopathology and cytokeratin-immunohistochemistry. Analysis of genomic DNA did not reveal p53 mutations nor were HPV sequences detectable. Risk factors included conditioning for BMT with total body irradiation (TBI) and cyclophosphamide (Cy), immunosuppressive treatment for GVHD, and extensive exposure to UV radiation before and after BMT. Despite surgery and adjuvant chemotherapy with 5-fluorouracil (5-FU) the patient died 1 year after the diagnosis of SCC.

Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease.

Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing compound 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in the treatment of several T-cell-mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. We present 21 patients (10 men and 11 women) with hematological malignancies with a median age of 36 years (range, 25 to 55 years) who had received marrow grafts from sibling (n = 12) or unrelated (n = 9) donors. Six patients had acute graft-versus-host disease (GVHD) grade II to III not responding to cyclosporine A (CSA) and prednisolone when referred to extracorporeal photochemotherapy (ECP). In 15 patients, 2 to 24 months after bone marrow transplantation (BMT), extensive chronic GVHD with involvement of skin (n = 15), liver (n = 10), oral mucosa (n = 11), ocular glands (n = 6), and thrombocytopenia (n = 3) developed and was unresponsive to conventional therapy, including steroids. All patients were treated with ECP on 2 consecutive days every 2 weeks for the first 3 months and thereafter every 4 weeks until resolution of GVHD. ECP was tolerated excellently without any significant side effects. After a median of 14 cycles of ECP, acute GVHD resolved completely in 4 of 6 patients (67%) and partially in another 2 patients. Cutaneous chronic GVHD completely resolved in 12 of 15 (80%) patients. Contractures of knees and elbows due to scleroderma resolved partially. Oral mucosal ulcerations resolved in all patients. Seven of 10 patients (70%) with liver involvement had complete responses after ECP. After discontinuation of ECP, no severe infections were observed. Our findings suggest that ECP is a safe and effective adjunct therapy for both acute and extensive chronic GVHD with skin and visceral involvement and resistance to conventional therapy.

[Management of HIV infected patients: applicability of guidelines. Results of an nationwide Austrian survey]. / Management HIV-infizierter Patienten: Anwendbarkeit von Richtlinien. Ergebnisse einer österreichweiten Umfrage.

BACKGROUND: Antiretroviral treatment and prophylaxis in HIV-infected patients follows guidelines. Aim of the study was to evaluate to what extent guidelines are useful. We used a cohort of patients (I) and a nationwide audit (II). SUBJECTS AND METHODS: Over a 48-month period demographic data, immunologic function and stage of HIV-infection of 433 patients were recorded (I). Questionnaires about the practicability of antiretroviral therapy according to recently published guidelines were mailed to experienced hospital departments and private offices (II). RESULTS: I. In 307 of 433 (70.9%) patients antiretroviral therapy and in 107 of these 433 (24.7%) patients primary prophylaxis against PC-infection could be initiated according to the guidelines. In 21 of 433 patients (4.8%) Ganciclovir prophylaxis was applicated using Port-a-Cath systems in a homecare setting. II. In Austria 118 questionnaires were mailed in June 1996, 43 (36.4%) were returned and 38 could be evaluated. 1450 patients were treated by physicians, who answered the questionnaires, 78.1% of these worked in hospitals and 78.9% were specialists. 75% of the physicians had experience with HIV-infected patients exceeding 5 years. CD4+ lymphocyte count was routinely done in 73.7% of the physicians, viral load only in 42.1%. These examinations were predominantly performed in hospitals (in 64.3% and 81.2%, respectively). Only 13/36 of the physicians prescribed the recommended combination therapy consisting of 2 nucleosides and 1 protease-inhibitor. 5/6 hospitals and 4/8 private offices in Vienna and 6/12 hospitals outside of Vienna used proteaseinhibitors. CONCLUSIONS: Antiretroviral treatment according to the guidelines published recently, is only possible in centres for the treatment of HIV-infected patients at the moment.

Complete remission of lichen-planus-like graft-versus-host disease (GVHD) with extracorporeal photochemotherapy (ECP).

A 45-year-old female patient with CML underwent allogeneic BMT and developed two episodes of acute GVHD. The first episode of acute cutaneous GVHD grade II (day +17) responded well to systemic CsA and steroids. During the second episode (around day +60) the patient developed erythroderma (grade III), and subsequently signs of lichen-planus-like GVHD. The patient did not respond to increased dosages of prednisolone and CsA. On day +89 extracorporeal photochemotherapy (ECP) was initiated. After four cycles, a significant improvement of erythroderma and lichen-planus-like lesions was documented, and after 12 cycles, a lasting complete remission was achieved. To our knowledge this is the first report of successful treatment of early-onset, lichen-planus-like GVHD after allogeneic BMT with ECP.