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Biomedical subjects

J Agosti

Publications and source records attributed to J Agosti.

At least 19 recordsLinked to original sources

The safety and efficacy of GM-CSF as an adjuvant in hepatitis B vaccination of chronic hemodialysis patients who have failed primary vaccination.

BACKGROUND: End-stage renal disease and the need for chronic hemodialysis is an indication for hepatitis B vaccination, but up to half of dialysis patients fail to respond to a 40 microg/dose i.m. three-dose primary series of recombinant hepatitis B vaccine. Only another 10-20% respond to additional boosting doses of vaccine. PATIENTS AND METHODS: Since GM-CSF has been shown to be an effective adjuvant for hepatitis B vaccine in healthy subjects and multiple animal vaccine models, we conducted a randomized, double-blind trial of GM-CSF with recombinant hepatitis B vaccine in chronic hemodialysis patients. Patients with negative hepatitis B surface antibody and antigen who had received at least three doses of recombinant hepatitis B vaccine without response (antibody titre < 10 mIU/ml) were randomized to placebo, 40 microg, or 80 microg of GM-CSF given with 40 microg recombinant hepatitis B vaccine i.m. at the same site. Clinical and laboratory studies for safety assessment were done on days 1 and 3, and hepatitis B surface antibody titres were measured at baseline and days 21 and 180 after the study injections. RESULTS: No significant local or systemic toxicity was noted from the co-injections. The rates of response and geometric mean titre (GMT) were equivalent among all three study groups: placebo 6/10 developed antibodies, GMT 22.1 mIU/ml; 40 microg GM-CSF 3/10 developed antibodies, GMT 5.4 mIU; and 80 microg GM-CSF 3/8 developed antibodies, GMT 9.7 mIU/ml. Six months after vaccination, antibody titres were available for 11 of the 12 day 21 positive responders; only 4 of these 11 patients remained antibody positive at 6 months. CONCLUSION: GM-CSF given in a single 40 microg and 80 microg i.m. dose was not an effective adjuvant with hepatitis B vaccine in chronic hemodialysis patients who had previously failed to respond to hepatitis B immunization.

Adjuvants, Immunologic↗

A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates.

OBJECTIVE: We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs. STUDY DESIGN: VLBWNs (n = 264), weighing 501 to 1000 g, </=72 hours of age were randomly assigned to receive rhu GM-CSF (8 microg/kg/d), administered intravenously (n = 134) over 2 hours daily x 7 days and every other day for 21 days, or placebo (n = 130). The safety, incidence of nosocomial infections, days of absolute neutrophil count >/=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups. RESULTS: No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS). CONCLUSION: In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.

Cross Infection↗

Phase I/II trial of the type I soluble recombinant human interleukin-1 receptor in HIV-1-infected patients.

Interleukin-1 (IL-1) produced in peripheral blood mononuclear cell (PBMC) cultures or added exogenously has been shown to upregulate HIV expression in vitro. Inhibition of IL-1 in HIV-infected individuals may inhibit HIV activation and slow disease progression. Recombinant human IL-1 receptor (rHu-IL-1R), the soluble extracellular portion of the human type I IL-1 receptor, inhibits HIV expression in acutely infected primary PBMCs and in the chronically infected promonocytic cell line, U1. We, therefore, conducted a phase I/II trial of the soluble rHu-IL-1R in HIV-1-infected individuals with CD4 T cell counts <300/microl to evaluate its safety and activity. Twelve evaluable patients were enrolled at three rHu-IL-1R dose levels:125 (n=3), 500 (n=3), and 1250 (n=6) microg/m2 per dose by subcutaneous (s.c.) injection three times a week for 8 weeks, followed by a 4 week observation period. rHu-IL-1R was safe and well tolerated. There were no deaths, no treatment-related grade 3/4 events, and no premature study discontinuations because of adverse events. The maximum tolerated dose was not reached. Seven patients reported improvements in one or more symptoms, including weight gain (3), improved energy level (4), decreased diarrhea (1), decreased night sweats (1), improvement in psoriatic arthritis (1), and improvement in a nonspecific chronic diffuse skin rash (1). Of 3 evaluable patients with Kaposi's sarcoma, 1 remained stable and 2 showed minimal progression. No consistent trends in absolute CD4 counts or percentages, quantitative HIV cultures, or serum p24 antigen, beta2-microglobulin, or triglyceride levels were observed. rHu-IL-1R is safe and well tolerated at the doses tested but induced no consistent changes in objective markers of HIV disease. Symptomatic improvements will require confirmation in randomized, placebo-controlled trials.

Acquired Immunodeficiency Syndrome↗

Comparison of neutrophil and monocyte function by microbicidal cell-kill assay in patients with cancer receiving granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or no cytokine after cytotoxic chemotherapy: a phase II trial.

Functional effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were prospectively measured by harvesting blood samples from 51 oncology patients (21 who were receiving no cytokines, 14 receiving rhGM-CSF, and 16 who were receiving rhG-CSF) just before cytotoxic chemotherapy (baseline) immediately before the last cytokine dose (pre), 2 hours after the last cytokine dose (post), and 48 hours after the pre period (follow-up). Neutrophils and monocytes were separated and functional effects were measured by comparing cell-kill percentages, as determined by a microbial cell-kill assay against Staphylococcus aureus and Candida albicans. Optimal cell concentrations (2 x 10(6) monocytes/ml; 4 x 10(6) neutrophils/ml) and effector-to-cell ratios (1:50) were initially determined with blood samples harvested from 23 healthy volunteers. Results in oncology patients indicated that rhGM-CSF improved monocyte-killing activity against S. aureus at follow-up, compared with controls (p = 0.0094) and compared with monocytes from rhG-CSF-treated patients at the post period (p = 0.014). Cell-killing percentage of the rhGM-CSF-treated patients was also enhanced against C. albicans during the post period, compared with controls (p = 0.011) and rhG-CSF-treated patients (p = 0.067). Neutrophil activity was not altered by either cytokine. In conclusion, monocyte-induced microbial killing was enhanced in oncology patients receiving rhGM-CSF after cytotoxic chemotherapy, compared with patients receiving rhG-CSF or no cytokines. No differences in neutrophil activity were observed between patients receiving either cytokine.

Candida albicans↗

[Anomalous origin of the left coronary artery from the pulmonary artery in adults. Long-term follow up].

Anomalous origin of the left coronary artery from the pulmonary artery is a serious pathology, that untreated supposes a high mortality. Usually it becomes symptomatic in early infancy, but some cases reach adult life with no symptoms. We report four cases diagnosed in teenagers and adults, three of them with the oldest ages known in worldwide literature and one of them the oldest reported until now. We have completed a long follow-up in the various surgical techniques, where we did not observe any differences in their prognosis, and we recommend an anti-arrhythmia treatment joined with surgical treatment in adult patients with this pathology.

Adolescent↗

[Multiple aneurysms of the left auricula, ascending aorta and sinuses of Valsalva with interventricular communication, fibromuscular subaortic stenosis and a single coronary artery].

We report the case of a male newborn infant with aneurysm of atrial appendage, ascending aorta and sinus of Valsalva associated to ventricular septal defect, fibromuscular subaortic stenosis and single coronary artery. The diagnosis was carried out by means of two-dimensional echocardiography and angiocardiography. This complex cardiac malformation has not been reported before.

Abnormalities, Multiple↗

Tumor necrosis factors alpha and beta differ in their capacities to generate interleukin 1 release from human endothelial cells.

The capacity of the tumor necrosis factors, TNF-alpha and TNF-beta, products of activated macrophages and lymphocytes, respectively, to stimulate interleukin 1 (IL-1) release from endothelial cells derived from human umbilical veins was examined in vitro. Recombinant TNF-alpha caused IL-1 release by 4 hr with maximal levels of 17 U/ml by 24 hr; half-maximal stimulation occurred at approximately 80 pM. In contrast, recombinant TNF-beta was a relatively poor stimulus for IL-1 release. Even at concentrations as high as 600 pM, only 3 U of IL-1/ml were recovered; maximal IL-1 release (10 to 12 U/ml) required up to 5 nM TNF-beta. Natural, glycosated human TNF-beta was comparable in activity to recombinant TNF-beta. TNF-beta did not directly inhibit the IL-1 comitogenesis assay, nor was there evidence that TNF-beta induced the release of an IL-1 inhibitor, in that supernatants generated in the presence of TNF-beta did not inhibit thymocyte proliferation to a recombinant IL-1 standard. Binding of the recombinant TNF to endothelial monolayers was assessed by using [125I]TNF-alpha in competition studies with cold TNF-alpha and TNF-beta. Binding of TNF-alpha was half-maximal at 80 pM with an average of 664 receptors/cell and Kd = 0.043 nM. Although TNF-beta was capable of fully competing for [125I]TNF-alpha binding, half-maximal binding occurred at 800 pM TNF-beta. These data suggest that the TNF receptors on human endothelial cells may reflect the structural differences between these two homologous cytokines.

Cells, Cultured↗

Differential diagnosis of intrapericardial mass identified as venous ectasia.

The case of an infant with an intrapericardial mass identified as venous ectasia of the left cardinal vein is presented. Because of the few cases reported in the literature of this anomaly, we believe it is of interest to update its description as an intrapericardial venous cystic dilatation, congenital in origin, and unrelated to the pericardium or the heart. Our purpose is to describe this case as a hematic cyst arising from the ectasia dilatation of the left cardinal vein as an isolated entity originating in the fetal period.

Journal Article↗

Hemorrhagic colitis with Escherichia coli O157:H7 preceding adult hemolytic uremic syndrome.

Escherichia coli serotype O157:H7 is a rarely identified organism that has recently been associated with hemorrhagic colitis in all age groups and with the hemolytic uremic syndrome (HUS) in children. We now report the development of HUS in two young women following enteric infection with E coli O157:H7. Both patients were hospitalized because of the severity of their colitis. They later developed major hemolysis requiring transfusion and significant renal failure requiring, in one case, hemodialysis. One patient underwent laparotomy, where sterile ascites, marked right colonic edema, and intraserosal hemorrhage were noted. Both women survived and are currently improving. Fecal E coli serotype O157:H7 was sought only after routine cultures were negative and features of HUS were recognized. The search for the E coli was facilitated by the continued availability of stool cultures obtained early in the course of the illness. The source of infection was not ascertained, but ingestion of untreated water was a feature of both cases. The HUS is a potential complication of the hemorrhagic colitis associated with E coli serotype O157:H7 and may develop in adults as well as children following enteric infection with this organism.

Adult↗

Rheumatoid arthritis with severe aortic insufficiency and prolapse of the mitral valve.

The valvular lesions caused by rheumatoid arthritis have been known for a long time. The valves may be affected by unspecific inflammatory changes or, specifically, by rheumatoid granulomas identical with subcutaneous nodules that lead to the malfunctioning of the aortic or the mitral valve. We present a patient affected by a classical seropositive rheumatoid arthritis accompanied by a severe aortic insufficiency and a prolapse of the mitral valve with rheumatoid involvement of the histologic granulomatous type, in whom both valves were replaced in two phases. The hemodynamic results were good for a period of time. Replacement of the valve by a prosthesis is the ideal treatment. There is no experience with treatment such a medication with immunosuppressive drugs.

Aortic Valve Insufficiency↗

Pulmonary artery sling: case report and surgical management.

Surgical correction of pulmonary artery sling with vascular ring in a 2 1/2-year-old boy is described. Despite the high mortality rate of this entity, the post-operative course was uneventful and since hospital discharge, the boy has remained asymptomatic.

Journal Article↗

Dysfunction of the Björk-Shiley prosthesis. Report of 32 cases.

We present 32 cases of dysfunction of the Björk-Shiley valvular prosthesis, representing 3.01% of the 1,063 BS prostheses implanted at this clinic. The complications observed were thrombosis of the prosthesis, suture dehiscence with or without endocarditis and disc-suture interference. In selected, favourable cases, we prefer thrombectomy with generous washing of the prosthesis and rotation of the disc, without removal of the disc from the prosthesis. Furthermore, when the dehiscence does not exceed 1/3 of the circumference of the ring, we have achieved very good results with single sutures supported on Teflon patches. Subsequent failures of this procedure were not of a technique nature, but rather due to the poor condition of the patients. In situations of clinical emergency, the diagnosis of valvular dysfunction may suffice as indication of surgery, further diagnostic measures being postponed in view of the data of the physical exploration.

Adolescent↗