Angiotensin II receptor blockade in Syrian hamster (T0-2) cardiomyopathy does not affect microscopic cardiac material properties: implications for mechanisms of tissue remodeling

This study delineates the role of angiotensin II type I (AT1) receptor in the remodeling of Syrian cardiomyopathic hamsters. Twelve cardiomyopathic (T0-2) hamsters received L-158,809 treatment and libitum in their drinking water (27 micrograms/ml) and 9 cardiomyopathic and 9 normal FL-B hamsters received tap water from 1 to 4 months of age. Although pharmacologically effective with regard to complete suppression of the blood pressure response to angiotensin II infusion, L-158,809 did not diminish the progression or severity of cardiomyopathy. Heart weight/100 g body weight and left ventricular wall thickness adjusted for body weight of both L-158,809 and cardiomyopathic control hamsters did not differ and exceeded those of F1-B controls (p < 0.05). Myocardial material properties (e.g., stiffness and density) of cardiomyopathic hamsters treated with L-158,809 were not affected. Thus, the progression of fibrosis, calcification, and necrosis in T0-2 cardiomyopathic hamsters was not sensitive to AT1 receptor blockade.     

Role of hepatic resection in surgery for bilateral intrahepatic stones

The effect of phenylephrine-induced reflex parasympathetic stimulation on QT interval and its dispersion was studied in 16 healthy subjects with a history of paroxysmal supraventricular tachycardia, both during sinus rhythm and during atrial pacing. Results demonstrate that rapid reflex parasympathetic stimulation does not influence QT interval duration or QT dispersion, and also emphasize the inappropriateness of Bazett's formula, the need for comparison of QT intervals during identical heart rates, and the importance of analyzing all 12 leads of a standard electrocardiogram when assessing the effects of various interventions on the QT interval.     

Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained

The objectives of this study were to evaluate the protective effects of amifostine against paclitaxel-induced toxicity to normal and malignant human tissues. Haematopoietic progenitor colony assays were used to establish the number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT and alkaline elution assays evaluated the in vitro growth inhibitory and DNA damaging effects, respectively, of paclitaxel with or without amifostine against normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. This combination was also evaluated in vivo using severe combined immune deficient (scid) mouse models of early (non-palpable tumours) and advanced (palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were inoculated subcutaneously while paclitaxel and amifostine were administered intraperitoneally. A brief exposure (15 min) to amifostine not only protected human haematopoietic progenitor colonies from paclitaxel toxicity, but stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand breaks were actually enhanced by pretreatment with amifostine in the NSCLC model. Importantly, amifostine did not interfere with paclitaxel antitumour activity even with prolonged exposure (24.5 h) of the lung cancer cells to high concentrations (1.2 mM) in vitro or following five repetitive high doses (200 mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under certain circumstances, amifostine resulted in sensitisation of tumour cells to paclitaxel. Our results confirm previous reports of the ability of amifostine to protect normal tissues from the toxic effects of chemotherapy drugs and now extend these observations to paclitaxel.     

Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL

PURPOSE: We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia. PATIENTS AND METHODS: Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either < or = 10,000/microL or < or = 20,000/microL. RESULTS: There was no significant difference in the total number of bleeding episodes per patient with a median of four in the < or = 10,000/microL arm and two in the < or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the < or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the < or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the < or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications. CONCLUSION: Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.     

Accelerated lung function decline in swine confinement workers

We conducted a longitudinal study to determine the annual rate decline in pulmonary function measurements in male swine confinement workers. For comparison, a grain farming group and a nonfarming rural-dwelling control group were also chosen for the longitudinal study. Two hundred seventeen swine confinement workers, 218 grain farmers, and 179 nonfarming control subjects had valid pulmonary function measurements at the baseline observation conducted in 1990 to 1991 and at the second observation conducted in 1994 to 1995. The swine confinement workers were younger (mean age=38.3+/-11.7 [SD] years) than the nonfarming control subjects (42.6+/-10.4 years) and the grain farmers (44.5+/-11.9 years). When stratified by age, nonfarming control subjects had the lowest mean annual rate decline in FEV1 and FVC in all age categories. The swine confinement workers had the largest annual rate decline in FEV1 and FVC, and this was most obvious in the middle age categories. After controlling for age, height, smoking, and baseline pulmonary function, swine confinement workers had excess annual decline of 26.1 mL in FEV1 (p=0.0005), 33.5 mL in FVC (p=0.0002), and 42.0 mL/s in forced expiratory flow between 25% and 75% of FVC (FEF[25-75%]) (p=0.02) over nonfarming control subjects. Grain farmers had excess annual decline of 16.4 mL in FEV1 (p=0.03), 26.7 mL in FVC (p=0.002), and 11.2 mL/s in FEF(25-75%) (p=0.38) over control subjects. These findings suggest that workers engaged in the swine industry and grain farmers appear prone to accelerated yearly losses in lung function and may therefore be at risk for the future development of chronic airflow limitation.     

A recombinant adenovirus that directs secretion of biologically active kappa-bungarotoxin from mammalian cells

The purpose of this investigation was to develop a method that could be used to estimate how damaging sodium ethoxide is to different antigens with respect to immunolabeling when epoxy sections are deplasticized. If we obtain weak labeling for an antigen on deplasticized epoxy sections, this might be caused by the damaging effect of the ethoxide solution. It is therefore interesting to develop a method to check if this really is the reason. Fibrin clots and tissues of human kidney and thyroid were embedded in LR White resin. Some thin sections from these specimen blocks were exposed to sodium ethoxide in the same way as epoxy sections are when being deplasticized. Other sections from the same blocks were not exposed to sodium ethoxide. Both categories of sections were immunogold-labeled with anti-fibrinogen, anti-thyroglobulin, anti-IgA, anti-IgG, or anti-IgM. The intensity of immunolabeling of sections treated with ethoxide was compared with the immunolabeling of corresponding sections that were not treated with ethoxide. No significant differences were found in immunolabeling for fibrinogen, IgA, IgG, and IgM. For thyroglobulin, the intensity was approximately 30% less in tissues that were exposed to sodium ethoxide. The practical significance of this method is that we easily can examine the degree to which a given antigen is affected by sodium ethoxide, which is the agent used for deplasticizing epoxy sections.