Valve-related complications with the Hancock I porcine bioprosthesis. A twelve- to fourteen-year follow-up study

Valve-related morbidity and mortality after heart valve replacement with the Hancock I porcine bioprosthesis has been retrospectively analyzed. From June 1974 through December 1976, 253 Hancock I bioprostheses (150 mitral and 103 aortic) were inserted in 220 selected patients who survived the operation and had follow-up until June 1989 (mean follow-up 13.5 years, with an accumulative follow-up of 2956.4 patient-years). One hundred seventeen patients had mitral valve replacement, 70 had aortic valve replacement, and 33 had combined mitral and aortic valve replacement. There were 27 thromboembolic events. The probability of being free from thromboembolism at 14 years was 81.0% +/- 7.4% for the mitral valve replacement group, 85.4% +/- 6.7% for the aortic group, and 67.1% +/- 18.4% for the mitral-aortic group. Fifteen episodes of prosthetic valve endocarditis occurred. There were 10 instances of nonstructural dysfunction (paravalvular leaks) in seven mitral valves (4.6%) and in three aortic valves (2.9%). One hundred twenty-two bioprostheses in 106 patients resulted in structural deterioration. The probability of freedom from structural deterioration at 14 years was 37.2% +/- 3.9% for the mitral group, 43.9% +/- 7.1% for the aortic group, and 30.1% +/- 8.9% for the mitral-aortic group. The logistic regression analysis between age at the time of operation and bioprosthetic life (structural deterioration-free period) demonstrates a linear regression curve (r = 0.53). There were 56 late deaths (27 patients died at reoperation). The actuarial survival rate (including hospital mortality) at 14 years was 57.2% +/- 5.4% for the entire series, with no statistically significant difference between groups. The probability of remaining free from valve-related morbidity and mortality at 14 years was 16.7% +/- 4.8% for the mitral group, 20.8% +/- 6.2% for the aortic group, and 14.0% +/- 7.0% for the mitral-aortic group. The long-term results of this series show that the clinical performance of the Hancock I porcine valve appears satisfactory during the first 6 years. The behavior of this bioprosthesis at 14 years' follow-up changes drastically, because only a minor group of patients is free from valve-related complications, justifying the restriction of its use for selected patients.     

Steroid conversion and prostaglandin production by chorionic and decidual cells in relation to term and preterm labour

The production of progesterone from pregnenolone, of cortisol from cortisone and of prostaglandin E (PGE) under basal and arachidonic acid-stimulated conditions was measured in cells dispersed from chorion and decidua. The cells were obtained after delivery from four groups of women: following spontaneous labour at term (38-42 weeks gestation), at elective caesarean section at term before the onset of labour, after induced labour at term, and after uncomplicated preterm (27-36 weeks) labour. Chorionic cells had a high progesterone output with relatively low cortisol and PGE production, whereas decidual cells had a high cortisol and PGE production rate. Free arachidonic acid stimulated PGE production in both decidual and chorionic cells. There were no significant differences in either steroid or PGE production among the four groups studied. These data suggest that steroid dehydrogenase activity in choriodecidual cells is not related to the mode of onset of labour and that the increased prostaglandin production in intrauterine tissues associated with parturition is due to enhanced availability of arachidonic acid.     

Actin-free Gc globulin: a rapidly assessed biomarker of organ dysfunction in acute liver failure and cirrhosis.

Reductions in serum levels of Gc globulin, a hepatically synthesized component of the extracellular actin scavenger system responsible for complexing circulating actin and attenuating intravascular microthrombus formation, are associated with poor outcome in acute liver failure. Clinically applicable assays of the important actin-free fraction (Af-Gc) have not been available until now. We measured actin-free Gc globulin levels with a novel, rapid assay in 61 cases of acute liver failure (ALF) and in 91 patients with cirrhosis (40 of whom were clinically unstable with extrahepatic organ dysfunction), and studied associations with liver dysfunction, extrahepatic organ dysfunction, indices of disseminated coagulation, and outcome. Reductions in Af-Gc levels mirrored hepatic dysfunction and organ dysfunction in both groups, and discriminated patients with poor prognosis from those with good prognosis in the ALF cohort. Levels were lowest in patients with ALF (10% of control values), but levels were also markedly reduced in both unstable (28%) and stable (44%) patients with cirrhosis. Associations with markers of disseminated intravascular coagulation were seen in both groups, most notably in the cirrhosis cohort, supporting a pathophysiological role for reduced Af-Gc in the evolution of organ dysfunction. In acetaminophen-induced ALF, Af-Gc identified patients with poor prognosis as well as did the Acute Physiology and Chronic Health Evaluation (APACHE II) score (area under the receiver operating characteristic curve, 0.7), and in cirrhosis, Af-Gc was an independent predictor of mortality by multifactorial analysis. In conclusion, the importance of Af-Gc reductions in the development of multiple organ dysfunction in ALF and cirrhosis is highlighted, probably resulting from reduced hepatic production and peripheral exhaustion of this arm of the extracellular actin scavenger system.     

Seroepidemiological study of hepatitis E virus in different population groups

In order to determine the seroprevalence of hepatitis E virus, 1,993 sera (453 from healthy pregnant women, 491 from Moroccan subjects, 492 from blood donors, 321 from children, and 236 from intravenous drug users) were studied. IgG was measured by enzyme immunoassay (EIA), and positive results were confirmed by Western blot. The EIA detected antibodies in 3.96 % of the subjects (5.6 % of the Moroccans and drug users and 1.8 % of the children). Fifty-four percent of these results were confirmed by Western blot, 11.4 % were found to be negative, and 34.2 % indeterminate. The overall prevalence after confirmation by Western blot decreased to 2.15 %. When studying the Western blot pattern of the positive samples, 95 % showed antibodies to SG-3, 65 % to 8–5, and only 9.3 % to CKS fusion protein. In the indeterminate Western blots, the results for these proteins were 96.3 %, 62.9 %, and 37 %, respectively. When the epidemiological data were analysed, no statistically significant differences between women and men or between different age groups were found.     

Human papillomavirus detection: verification with cervical cytology.

OBJECTIVE: Thirteen specific types of human papillomavirus (HPV), classified as high-risk for the development of cervical cancer, have been reported in 99.7% of all cervical cancers. For this reason, and because of the reported lack of sensitivity of the Papanicolaou (Pap) smear for detecting HPV, some experts believe that the use of papillomavirus DNA testing may replace cytology for routine gynecological screening. Our goal was to validate a commercial assay, the Digene Hybrid Capture-2 for the detection of human papillomavirus by comparing the results to cytological detection of cervical abnormalities. DESIGN: Cytology results of concurrent liquid-based Papanicolaou smears were compared to the Hybrid Capture-2 results. Correlation was assessed and discordant cytology results were reviewed. SETTING: Louisiana State University Health Sciences Center at Shreveport, Department of Pathology, HPV Diagnostic Laboratory. PATIENTS: All liquid cytology specimens submitted for HPV testing between November 1, 2000 and April 1, 2001. RESULTS: Of the 291 cases tested by Hybrid Capture-2, 12% and 28% were positive with the low-risk and high-risk probes, respectively, and 265 had concurrent cytology results. Fourteen specimens testing positive only with the low-risk probe were not included in this comparison. Thus, the results for 251 of the 291 (86%) specimens tested for human papillomavirus DNA were compared to the original cytology report. Overall concordance between Hybrid Capture-2 and the original smear cytology result was 78%. Slide review reduced the number of discordant specimens from 22% to 12%. CONCLUSION: Based upon these data, we find the HPV assay to be useful as a routine screen for Human papillomavirus.     

Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite

The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function.     

Potentiation of FMD vaccines with polycationic-nucleic acid complexes

Summary The effect of various polycations on the immune response potentiated with poly I:C was studied. It was found that low molecular weight polycations had no potentiating effect. Polylysine was ineffective whereas protamine was superior to lysozyme, poly-arginine, poly-histidine, DEAE-Dextran and histone.A foot-and-mouth disease trivalent vaccine composed of strains A₂₄ Cruzeiro, O₁ Caseros and C₂ Resende elicited no immune response in swine when adjuvanted with aluminium hydroxide but was effective when emulsified in oil. In general, the immune response was potentiated ten-fold when the emulsion contained poly I:C. The antibody production was in most cases further potentiated by a factor of ten when the nucleic acid double-strand was complexed with 1:10 (w/w) DEAE-Dextran. Protamine was as effective, or perhaps even more, than DEAE-Dextran to this effect.Guinea pigs vaccinated with a water-in-oil emulsion type monovalent C₃ vaccine showed an increase in antibody production when the vaccine contained poly I:C or poly I:C complexed with 1:10 (w/w) protamine.With 4 Figures     

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.     

Broad band spectral EEG parameters correlated with different IQ measurements

The relationship of IQ (measured by WAIS and all its subscales) and EEG broad band spectral parameters were studied in 40 right-handed, male volunteers ranging in age from 20 to 25 years old. EEGs were recorded in 20 derivations during rest with eyes opened. The results obtained reveal positive and negative correlations with abundant frontal participation in all bands. Mean frequency data show a frequency shift in a very narrow range suggesting that more relations in narrow band could be achieved. These results highlight the need of psychological tests that measure more homogeneous abilities and finer measurement technique to reveal clearly explainable correlations and demonstrate that EEG recordings do reflect intellectual abilities.