A phase III study of recombinant human interferon gamma to prevent opportunistic infections in advanced HIV disease.

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.

In vivo experimental assessment of polytetrafluoroethylene trileaflet heart valve prosthesis.

This report summarizes the results of a series of experimental implantations of polytetrafluoroethylene valves in sheep. Twelve prostheses were implanted in the tricuspid position in weanling (3- to 4-month-old, 26 +/- 3 kg) sheep. The valve sizes were 23 mm (eight animals) and 25 mm (four animals). There were two early deaths, and the 10 survivors were killed in a stepwise manner to get a mineralization profile of the valve. There was one episode of acute thrombosis but no evidence of pulmonary thromboemboli in any animal. In all cases the leaflets were thin and unretracted, but in half of them one cusp or more were stiffened. One valve displayed a fixed outward eversion of the free margin of two leaflets. Macroscopic calcification was detected in seven specimens and always involved the commissural areas. Radiologic studies confirmed this calcium topography and revealed only one case of severe and diffuse mineralization. In most cases the cusps showed a grossly visible pannus that was thinner and less extensive than usually seen in bioprostheses. Examination with light microscopy disclosed a complete lack of infiltrating cells within the cuspal material (made of compact polytetrafluoroethylene). However, those parts of the prostheses made of expanded polytetrafluoroethylene (the material covering the valve frame and the sutures) did show infiltration by host cells and calcium. Mineralized lesions were of extrinsic type, involving fibrin and fibroelastic host tissue accumulated in the inflow aspect of the commissures. Examination with transmission electron microscopy disclosed electron-dense masses surrounded by an electron-lucent granular homogeneous material in areas of mineralization. The time-course evolution of the tissue calcium content shows a moderate mineralization rate (0.46 +/- 0.31 mg/gm of dry-weight material per week of follow-up) and a marginally significant positive correlation between calcium content and follow-up. Our results suggest that the polytetrafluoroethylene valves have a moderate overall calcification rate and that calcium deposits appear to be always related to the commissural region and to the presence of expanded polytetrafluoroethylene.

Comparative study of primary tissue failure between porcine (Hancock and Carpentier-Edwards) and bovine pericardial (Ionescu-Shiley) bioprostheses in the aortic position at five- to nine-year follow-up.

Retrospective follow-up data on 458 consecutive patients who received a Hancock, Carpentier-Edwards (C-E) or Ionescu-Shiley (I-S) bioprosthesis in the aortic valve position between April 1978 and December 1981 are reviewed. A total of 461 valves (184 Hancock, 131 C-E and 146 I-S) were available for study of the incidence of primary tissue valve failure after 5 to 9 years of follow-up. Cumulative follow-up was 1,016 patient-years for patients with Hancock valve, 688 for the C-E and 767 for the I-S group. Of the 397 prostheses at risk (154 Hancock, 120 C-E and 123 I-S), 36 instances of primary tissue valve failure occurred (12 Hancock, 7 C-E and 17 I-S). On an actuarial basis, the calculated probability of freedom from primary tissue valve failure was 88 +/- 4% for the Hancock group, 87 +/- 6% for the C-E and 51 +/- 17% for the I-S at 9 years. The linear incidence of tissue valve failure was 1.2 failing valves per 100 patient-years for the Hancock group, 1 for the C-E and 2.2 for the I-S. In a cohort of patients older than 40 years of age at the time of valve replacement, the rate of freedom from primary failure was 98 +/- 1%, 87 +/- 9% and 44 +/- 22% for the Hancock, C-E and I-S groups, respectively, at 9 years. Comparison of actuarial curves disclosed a meaningful difference between the pericardial valve and the Hancock and C-E porcine bioprostheses at 9-year follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of primary tissue valve failure in porcine bioprosthetic heart valves.

This report provides retrospective follow-up data on 324 consecutive patients who received a Hancock-I porcine valve in the aortic or the mitral position, or in both positions, between June, 1974, and December, 1976. This analysis included 319 valves (193 mitral, 126 aortic) available for study of the incidence of primary tissue valve failure after 10 to 12.5 years of follow-up. Of the 319 prostheses at risk, 114 instances of primary tissue valve failure occurred. Seventy-three of the failed valves were in the mitral position, and 41 were in the aortic position. The calculated actuarial probability of freedom from primary tissue valve failure was 52 +/- 5% for the mitral and 58 +/- 6% for the aortic prostheses at 12.5 years of follow-up. For patients older than 40 years at the time of operation, the rate of freedom from primary failure was 68 +/- 8% and 55 +/- 6% for aortic and mitral prostheses, respectively, at 12.5 years. Comparison of both actuarial curves disclosed no meaningful difference. However, a tendency toward greater failure rate was observed in the mitral prosthesis group.

Long-term performance of porcine heart valve bioprostheses.

To assess the results after long-term implantation of porcine bioprosthetic heart valves, 320 patients with 381 valves were retrospectively reviewed. This group included all patients receiving one such xenograft in the mitral or aortic position (or both) in our institution between June 1974 and December 1976. The patients had a follow-up of 9-11.5 years. Actuarial patient survival rats (hospital mortality excluded) were 85%-90% at 6 years and 68%-79% at 11.5 years. Thromboembolic episodes did not show any significant clustering over the first weeks or months, in fact, they appeared at a constant rate. Actuarial rates of freedom from thromboembolism were greater than 90% for aortic patients at 11.5 years and greater than 80% for mitral and mitroaortic patients at 11.5 years. The linearized rate of anticoagulant-related haemorrhage for the whole group of patients was 0.4 events/100 patient years with a related mortality of 0.2 events/100 patient years. Prosthetic valve endocarditis and paravalvular leak appeared at linearized rates of 0.6 (0.1 of related mortality) and 0.4 (0.1 of related mortality) events/100 patient years. Primary tissue valve failure constituted the most prevalent complication (82 cases) in the long term but did not significantly worsen patient survival. Actuarial rates of freedom from primary tissue failure were 91% +/- 2% at 6, and 40% +/- 14% at 11.5 years for mitral valves, and 95% +/- 4% at 6 and 64% +/- 6% at 11.5 years for aortic valves.(ABSTRACT TRUNCATED AT 250 WORDS)