Background: There are no optimal practice guidelines for heart failure (HF) management in patients considered for cardiac transplantation (TXPL) . Limited data exist regarding the use of Nesiritide (NES) in this population. We reviewed our use of NES in inotrope-dependent pts being considered for cardiac TXPL that presented with high pulmonary capilary wedge pressure (PCWP) and pulmonary hypertension.

Background. The aim of this study was to define the potential for long-term survival with severe left ventricular dysfunction after coronary bypass and to quantify any improvement in overall functional status.Methods. Left ventricular dysfunction was confirmed preoperatively and the long-term survival and functional outcome after bypass was determined by follow-up studies obtained during the span of a decade.Results. From 1/1990 to 12/1999, 86 patients with severe left ventricular dysfunction (mean ejection fraction, 0.18 +/- 0.03; range, 0.10 to 0.20) underwent coronary artery bypass grafting. There were 10 perioperative deaths (11% mortality). The mean survival was 55 months (standard deviation +/- 34 months; range, 2 to 141 months) with an actual 5-year survival rate of 59% (actuarial 5-year 65%, 10-year 33%). Echocardiography obtained between 1 and 6 months, 6 months and 1 year, 1 and 2 years, 2 and 4 years, 4 and 6 years, and 6 and 11 years showed the ejection fraction improved to 0.29 +/- 0.08 (p < 0.001), 0.31 +/- 0.14 (p < 0.002), 0.35 +/- 0.08 (p < 0.001), 0.27 +/- 0.10 (p = 0.002), 0.36 +/- 0.14 (p = 0.004), and 0.30 +/- 0.11 (p = 0.004), respectively. At 1 to 6 months, 6 months to 1 year, and 1 to 2 years, the diastolic left ventricular dimension was unchanged, but the systolic left ventricular dimension decreased significantly from 5.02 +/- 0.77 cm to 4.26 +/- 0.91 cm (P = 0.046), 3.98 +/- 1.43 cm (P = 0.08), and 4.10 +/- 1.14 cm (p = 0.07). The preoperative New York Heart Association classification for all patients improved from 2.8 +/- 0.8 to 1.6 +/- 0.7 (p < 0.001) after a mean of 53 months (standard deviation +/- 34 months).Conclusions. Patients with severe left ventricular dysfunction can derive long-term benefit from coronary bypass through improved left ventricular contractility as documented by a significantly decreased systolic left ventricular dimension and increased ejection fraction. Successful bypass is associated with a 59% actual 5-year survival rate and significantly improved New York Heart Association functional class. (C) 2002 by The Society of Thoracic Surgeons.

Background:Basiliximab, a chimeric monoclonal antibody which blocks the α-chain of the IL-2 receptor complex, reduces acute rejection episodes in renal transplant recipients. Daclizumab (a similar monoclonal product)has been shown to reduce the incidence of acute rejection in lung transplant patients. We recently added basiliximab to our immunosuppressive regimen and hypothesized that a similar reduction in acute rejection would be noted.

Temporary, reversible inhibition of platelets during cardiopulmonary bypass is an attractive strategy to protect platelets and normalize postoperative bleeding times. Iloprost, an analogue of prostacyclin, and the disintegrins reversibly inhibit platelets by different mechanisms. We tested the hypothesis that reduced doses of iloprost and either echistatin, a natural disintegrin, or RO43-5054, a peptidomimetic, in combination provide better platelet protection than any drug alone during simulated extracorporeal circulation. Thirty-five recirculation studies using fresh, heparinized human blood in an extracorporeal perfusion circuit that contained a 0.45-m2 spiral coil membrane oxygenator were performed. Iloprost, but neither echistatin nor RO43-5054, increased platelet cyclic adenosine monophosphate. Combinations of iloprost and either fibrinogen receptor antagonist at reduced doses submaximally increased platelet cyclic adenosine monophosphate. Platelet adhesion and release of beta-thromboglobulin antigen was completely inhibited by combinations of the two classes of drugs, but only partially inhibited by each drug alone. Combinations of drugs also completely inhibited platelet aggregation to adenosine diphosphate; these platelets retained full sensitivity to adenosine diphosphate after 90 minutes of recirculation when drugs were removed by gel filtration. We conclude that combinations of iloprost and a fibrinogen receptor antagonist at doses that are unlikely to produce clinical side effects completely inhibit platelet activation and preserve platelet function during in vitro extracorporeal circulation.

The ability of recombinant platelet factor 4 and protamine to neutralize heparin after cardiopulmonary bypass was compared in anesthestized baboons. Clotting titration curves of heparinized baboon blood demonstrate an anticoagulant effect of protamine that is not seen with recombinant platelet factor 4. Neither drug caused meaningful changes in central pressures or cardiac output within 30 minutes after injection. After 30 minutes of cardiopulmonary bypass, recombinant platelet factor 4 normalized thrombin times and activated partial thromboplastin times within 5 minutes of injection, but protamine did not. Neither drug altered bleeding times. Recombinant platelet factor 4 caused a species-specific leukopenia in baboons and significantly increased activated complement protein 3 (C3a) more than protamine, However, the increase in plasma C3a was small and neither drug caused a significant increase in plasma neutrophil elastase-cu, proteinase inhibitor complex, We conclude that recombinant platelet factor 4 is effective and safe in baboons, does not have an anticoagulant effect with excess concentration, and reverses in vivo heparin more rapidly than protamine. The data support progression to a clinical trial.

Certain forms of extracorporeal circulation exemplified by cardiopulmonary bypass require continuous high-dose anticoagulation to prevent thromboembolic complications. We hypothesized that monocytes may be stimulated to express tissue factor (TF) during prolonged simulated extracorporeal circulation. TF was identified both by flow cytometry by using three TF-specific monoclonal antibodies and functional assay of procoagulant activity (PCA). TF significantly increased between 2 and 6 hours of simulated extracorporeal circulation by both analyses. Relative fluorescence on monocytes increased from a control value of 100 to 313 +/- 79 on cells from the simulated extracorporeal circuit (p < 0.05). PCA increased from 21 +/- 8 to 775 +/- 326 pg TF/10(6) monocytes (p < 0.05) and was blocked 99.6% by preincubation of cells with a mixture of monoclonal antibodies to TF. By 6 hours, the number of leukocytes in the circuit was decreased by 43%. The cells were recovered from the oxygenator membrane by washing with EDTA. Compared with initial values, by 6 hours, both TF antigen at 378 +/- 90 (p < 0.05) and PCA at 1,357 +/- 280 pg TF/10(6) monocytes (p < 0.01) were highest in the recovered cells. Cells incubated for 6 hours and not subjected to simulated extracorporeal circulation did not increase TF. Examination of monocytes for the adhesive receptor CD11b/18 (Mac-1) paralleled TF expression, providing an additional putative receptor for the coagulant proteins, factor X and fibrinogen or fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

The leukocyte integrin Mac-1 (alpha m beta 2, CD11b/18 CR3, MO1), in addition to binding iC3b, has been shown to be the receptor for the coagulation proteins fibrinogen, factor X, and high molecular weight kininogen. Mac-1 is known to be upregulated by agonists that stimulate neutrophils or monocytes. Previous studies from this laboratory have documented neutrophil activation during cardiopulmonary bypass. We therefore used an experimental model for cardiopulmonary bypass, a simulated extracorporeal circulation, to study the surface expression of Mac-1 on peripheral blood leukocytes by immunofluorescence flow cytometry. The number of Mac-1 receptors in polymorphonuclear leukocytes had increased 2.2 times and 2.9 times baseline by 2 hours at 37 degrees C and 28 degrees C, respectively (p < 0.001). Neutrophil elastase-alpha 1-proteinase inhibitor complexes (a measure of neutrophil degranulation) increased more than sixfold from 41 micrograms/L to 256 micrograms/L after 2 hours at 28 degrees C. The number of Mac-1 receptors expressed on polymorphonuclear leukocytes correlated with polymorphonuclear leukocyte elastase complexes (r = 0.93). Mac-1--bearing lymphocytes did not display any change in receptor number in the simulated extracorporeal circulation. By 2 hours, monocytes at 37 degrees C showed only insignificant increase; at 28 degrees C they displayed a 1.6 times increase (p < 0.05). By maintaining a temperature-matched standing control samples, we could prove that, unlike the Mac-1 in polymorphonuclear leukocytes, this increase in monocyte Mac-1 is not from bypass but is rather an effect of temperature. These data suggest that a receptor for procoagulant proteins on circulating polymorphonuclear leukocytes (Mac-1) is upregulated during simulated extracorporeal circulation.

Nowadays new sophisticated techniques of molecular biology based on the principles of hybridization between nucleic acids, allow a correct diagnosis of genital HPV infection. In the present paper, beside traditional diagnostic methods, we used In Situ Hybridization (ISH) and Polymerase Chain Reaction (PCR) to detect the presence of HPV types 6, 11, 16, 18, 31 and 33. We tested ten patients affected by cervical lesions of high histological atypias associated with HPV, who underwent surgical conization. Types 6 and 11, at low risk of evolution, are less frequent than 31 and 33, at medium grade of evolution, and than 16 and 18 which are at high risk of evolution.

The effect of exogenous dehydroepiandrosterone-sulfate (DHAS) on luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and thyroid-stimulating hormone (TSH) pituitary secretion was studied in 8 normal women during the early follicular phase. The plasma levels of these hormones were evaluated after gonadotropin-releasing hormone (GnRH)/thyrotropin-releasing hormone (TRH) stimulation performed after placebo or after 30 mg DHAS i.v. administration. The half-life of DHAS was also calculated on two subjects; two main components of decay were detected with half-times of 0.73-1.08 and 23.1-28.8 h. The results show an adequate response of all hormones to GnRH or TRH tests which was not significantly modified, in the case of LH, FSH and PRL, when performed in the presence of high levels of DHAS. However, the TSH response to TRH was significantly less suppressed (p less than 0.05) (39%) after DHAS administration than during repeated TRH stimulation without DHAS (51%). The data support the hypothesis that DHAS does not affect LH, FSH and PRL secretion, while TSH seemed to be partially influenced.

The behavior of tumor-associated trypsin inhibitor (TATI) as a marker for gynecological cancer was studied in a control population and in patients with different benign and malignant diseases. When a cut-off level of 21.4 micrograms/l was used the specificity was 100% in patients with benign diseases. The sensitivity in patients with malignant tumors was low for cervical and corpus cancer, 13% and 14%, respectively, whereas it was 33% in all the ovarian malignant tumors, reaching 60% in the mucinous type. There was a clear correlation between TATI level and stage.

The present study aims to evaluate the contraceptive efficacy of the new combination ethinylestradiol (30 micrograms)/desogestrel (150 micrograms) and, moreover, to demonstrate its low side effects compared to the symptoms present in the pretreatment cycles. In particular the authors took into consideration the changes in serum lipids, and hepatic and coagulation function parameters induced by pill, in 40 healthy women. An interesting result is that the estrogen induced increase of cholesterol-HDL is not antagonized by the desogestrel that has a slight affinity to androgenic receptors and SHBG. This is obviously of great importance in the prevention of atheromatous lesions.

SUMMARYΔ5 and Δ4 steroid levels were studied in the plasma and cyst fluid of women with gross cystic breast disease (GCBD). In luteal phase a significant increase in plasma levels (mean + SEM) of DHA (11.2 ± 2.4 ng/ml), DHAS (1.45 ± 0.6 fig/ ml) and Cortisol 277 ± 15.7 ng/ml) was found; in follicular phase the mean levels were 4.09 ± 0.47 ng/ml for DHA, 0.65 ± 0.08 μg/ml for DHAS and 190 ± 46.3 μg/ml for Cortisol. The DHA/DHAS and cortisol/androstenedione ratios were significantly higher in the plasma and lower in the cyst fluid of GCBD patients, than in the plasma of controls; the androstenedione/DHA ratio was higher in the cyst fluid than in the plasma of controls. The hormonal situation of the GCBD patients thus differed from that of the controls both in the plasma and cyst fluid, particularly as regards the Δ5 steroids.

synopsis Electro-convulsive treatment (ECT) was therapeutically ineffective in 27 (20 %) of 136 depressed patients. Failure to respond occurred in long-lasting depressions and in patients with a history of long-lasting depressions. In these cases the depression lasted at least 6 months. The hypothesis is proposed that ECT is effective only when given within 6 months of the spontaneous end of the depression. Clinical and nosological implications are discussed.