PubMed Health⌕ Search

Biomedical subjects

B J Ransil

Publications and source records attributed to B J Ransil.

At least 55 records · Page 3Linked to original sources

Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy.

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post-BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.

Adult↗

Spectrophotometric analysis of follicular fluid related to oocyte fertilization, embryo cleavage, and follicular fluid protein and hormone content.

Spectrophotometric absorbance patterns of follicular fluids (FF) obtained from in vitro fertilization patients were analyzed and compared with oocyte fertilization and embryo cleavage rates. Each absorbance pattern was resolved into three components: delta OD360, delta OD415, and delta OD455. A positive correlation was found between fertilization outcome and delta OD455. The absorbances were not related to embryo cleavage rates. We confirmed the presence of bilirubin and beta-carotene in FF: these pigments absorb at 455 nm and are most likely serum-derived. To explain the association between delta OD455 and fertilization, we hypothesized that the FF delta OD455 is a marker of the degree of vascularization of the follicle that could be assessed by FF protein and hormone concentrations. However, no correlation was found between the delta OD455 and these FF parameters, suggesting an alternative explanation for this association.

Body Fluids↗

The effects of cocaine on intracellular Ca2+ handling and myofilament Ca2+ responsiveness of ferret ventricular myocardium.

1. When ferret right ventricular papillary muscles were stimulated with threshold punctate pulses (0.33 Hz; 30 degrees C), cocaine, 10(-5) M, increased peak tension development from 815 +/- 120 to 1125 +/- 180 mg (P less than 0.05) and increased the rate of relaxation from peak tension (time to 80% decline from peak tension decreased from 155 +/- 11 to 144 +/- 11 ms; P less than 0.05). These changes in the twitch were associated with comparable changes in the amplitude and time course of the calcium transient measured with aequorin (amplitude increased from 62 +/- 4 to 90 +/- 7% (P less than 0.05) of maximal values; time to 80% decline from peak amplitude decreased from 84 +/- 8 to 64 +/- 3 ms; P less than 0.05). These effects were markedly attenuated in the presence of the beta-adrenoceptor-blocking agent, propranolol, 6 x 10(-7) M, or by maximization of catecholamine release from the adrenergic nerve endings with field pulses of suprathreshold strength, indicating that catecholamine release from the adrenergic nerve endings is responsible for the positive inotropic and lusitropic responses to low and moderate doses of cocaine (i.e., less than or equal to 10(-5) M). 2. High doses of cocaine (i.e., greater than 10(-5) M) produced negative inotropic and lusitropic effects that were associated with a decreased amplitude and prolonged duration of the calcium transient. 3. In aequorin-loaded intact fibres, cocaine 10(-5) M did not affect the force-calcium relationship unless catecholamines were present. Cocaine, 10(-5) M, significantly shifted the force-calcium relationship of saponin-skinned muscles (pCa50 = 6.14 +/- 0.05 versus 5.92 +/- 0.07; P less than 0.05), indicating reduced responsiveness of the myofilaments to calcium. F. (maximal Ca2+-activated force) was reduced to 58% of control in the presence of 10- M cocaine, while the slope of the calcium-force curve remained unchanged. These data indicate that cocaine may also decrease myofilament calcium sensitivity and maximal calciumactivated force, via mechanisms independent of catecholamines, when cellular diffusion barriers are eliminated.

Actin Cytoskeleton↗

Differential effects of cardiac hypertrophy and failure on right versus left ventricular calcium activation.

We studied calcium responsiveness of skinned muscle preparations from the right and left ventricles of rats with cardiac hypertrophy and cardiac hypertrophy plus failure. To test the hypothesis that differences in contractile function are due to changes in myofilament calcium responsiveness, we compared preparations from spontaneously hypertensive rats with cardiac failure, spontaneously hypertensive rats without cardiac failure, and age-matched normotensive Wistar-Kyoto control rats 18-24 months of age. Rats with failure had pleural/pericardial effusions, left atrial thrombi, and right and left ventricular hypertrophy. Muscles were skinned by saponin (250 micrograms/ml) and activated with a series of calcium buffers. Data were plotted as pCa (-log[Ca2+]) versus isometric force and then fit to a modified Hill equation. Values for 50% maximal activation (calcium sensitivity), maximal calcium-activated force, and the slope of the calcium-force relation were compared. Our data indicate that with the development of hypertrophy, calcium sensitivity of left ventricular muscles remains unaffected, but maximal calcium-activated force is increased. In contrast, maximal calcium-activated force declines toward control levels with the development of left ventricular failure, despite the continued presence of significant hypertrophy. In the normotensive rats, the left ventricle is more sensitive to calcium than the right ventricle (pCa50 = 6.0 +/- 0.05 versus 5.7 +/- 0.09; p less than 0.05); however, both the calcium sensitivity and maximal calcium-activated force of the right ventricle increase with the development of compensatory hypertrophy secondary to left ventricular failure. These changes that occur in rats with cardiac hypertrophy and failure may represent important physiological adaptive mechanisms.

Actin Cytoskeleton↗

Effects of MCI-154 on Ca2+ activation of skinned human myocardium.

We investigated the effects of MCI-154, a new inotropic agent, on tension development in saponin-skinned human trabeculae carneae. The skinned fibers were activated by buffer solutions containing varying concentrations of Ca2+ (10(-8)-10(-4) M). In the sigmoidal tension vs. pCa (-log[Ca2+]M) relationship, the Ca2+ concentration required for half-maximal activation was shifted leftward in the presence of MCI-154. Furthermore, maximal Ca2+-activated tension development was increased in a concentration-dependent manner by MCI-154. Our results suggest that the inotropic effect of MCI-154 may be due, in part, to an increased sensitivity of the myofilaments to Ca2+ and enhancement of maximal Ca2+-activated tension development.

Calcium↗

Onset of action between bupivacaine 0.5% and bupivacaine 0.5% plus fentanyl 75 mcg.

This study tested the hypothesis that the addition of fentanyl 75 mcg to bupivacaine 0.5% at the onset of epidural anesthesia for cesarean section reduces the onset time for T4 sensory blockade. The study was conducted in a randomized, double-blind fashion. The same observer performed sensory testing using pain to pinprick. Fourteen ASA I patients scheduled for elective cesarean section had epidural catheters placed. Group 1 (n = 7) received bupivacaine 0.5%, and group 2 (n = 7) received bupivacaine 0.5% plus fentanyl 75 mcg. Patients 5'0'' to 5'4'' in height received 15 ml, and patients 5'5'' to 5'9'' received 20 ml of bupivacaine. There were no adverse effects on the neonate or clinically important changes in maternal hemodynamics. The maternal age, height, weight, and bupivacaine dose did not differ between groups (p greater than 0.05). For group 1, the mean times for sensory loss at T7, T6, T5, and T4 were 13.1 +/- 3.8 minutes, 15.0 +/- 4.0 minutes, 16.9 +/- 4.3 minutes, and 19.3 +/- 4.9 minutes, respectively; for group 2, the mean times were 8.1 +/- 0.9 minutes, 9.9 +/- 1.1 minutes, 11.3 +/- 1.5 minutes, and 12.7 +/- 2.0 minutes, respectively. Two-factor analysis of variance between groups 1 and 2 showed a significant difference (p less than 0.0001), representing a 35% reduction of mean onset time. The coefficient of variation of the mean onset times for group 1 subjects was 26.6% +/- 1.7% and for group 2 subjects 12.7% +/- 2.2% (p less than 0.001), representing a 50% reduction in between-subject variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phosphatidylinositol-specific phospholipase C, a possible virulence factor of Staphylococcus aureus.

Phosphatidylinositol-specific phospholipase C (PIPLC), an enzyme that can specifically release phosphatidylinositol-linked proteins from host cells, is one of the extracellular enzymes produced by Staphylococcus aureus. To investigate whether PIPLC might be a virulence factor, we assessed PIPLC production by S. aureus strains that had been isolated from healthy carriers and from infected patients with or without toxic shock syndrome. Although none of five vaginal isolates from healthy women was a PIPLC producer, only 10 of 32 selected pathogenic strains that caused significant infections or toxic shock syndrome elaborated PIPLC enzyme activity. Seven of 24 toxic-shock-associated strains, compared with 3 of 8 non-toxic-shock-associated strains, were positive for PIPLC. The majority of strains that produced PIPLC were negative for toxic shock syndrome toxin 1 (P less than 0.05); this association between PIPLC production and strains negative for toxic shock syndrome toxin 1 was even stronger among strains isolated only from patients with toxic shock syndrome (P less than 0.01). Among all 32 pathogenic isolates, PIPLC-producing S. aureus strains were isolated from four of four patients developing adult respiratory distress syndrome and four of five patients with disseminated intravascular coagulation, suggesting a significant association between PIPLC production and adult respiratory distress syndrome and/or disseminated intravascular coagulation (P less than 0.002). On the basis of these results, we propose that PIPLC is a virulence factor of S. aureus and is implicated in the development of adult respiratory distress syndrome and disseminated intravascular coagulation.

Carrier State↗

Interaction of uridine 5'-diphosphoglucuronic acid with microsomal UDP-glucuronosyltransferase in primate liver: the facilitating role of uridine 5'-diphospho-N-acetylglucosamine.

Cytosolic uridine 5'-diphosphoglucuronic acid is the essential cosubstrate for all hepatic microsomal UDP-glucuronosyltransferase-mediated reactions. Uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc) has been implicated as an activator of UDP-glucuronosyltransferases in vivo, acting either as an allosteric effector or by enhancing access of uridine 5'-diphosphoglucuronic acid to the enzyme. To delineate the interaction of uridine 5'-diphosphoglucuronic acid with microsomal UDP-glucuronosyltransferase and the facilitating role of UDP-GlcNAc, we analyzed bilirubin UDP-glucuronosyltransferase kinetics in microsomes prepared from monkey liver (Macaca fascicularis). Initial rates of bilirubin glucuronide formation were determined by radiochemical assay over a range of uridine 5'-diphosphoglucuronic acid concentrations (0-60 mM), in native microsomes with or without UDP-GlcNAc, or in detergent (digitonin)-pretreated membranes with UDP-GlcNAc. For native microsomes in the absence of UDP-GlcNAc, fitting the data to each of two mathematical models yielded behavior consistent with a single-site model (Km 2.8 mM). In contrast, in the presence of a physiologic concentration (1 mM) of UDP-GlcNAc, analysis of the data excluded the single-site model and was indicative of a non-interactive, two-site (or process) model, characterized by a high-affinity site (Km 0.14 mM) in addition to the low-affinity site. Following detergent-treatment of microsomal membranes, the data were again most consistent with a single low-affinity site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hemorrhage, infection, toxemia, and cardiac disease, 1954-85: causes for their declining role in maternal mortality.

Hemorrhage, infection, toxemia, and cardiac disease are no longer the leading causes of maternal death. We studied factors causing their decline in incidence using data collected by the Committee on Maternal Welfare of the Massachusetts Medical Society between 1954 and 1985. The dramatic decline in incidence of these conditions in the Commonwealth during the study period appears to have been due to both legislative actions and improvements in medical practice. The legislative actions included licensing of maternity services, blood banks, and legalization of abortion. Cardiac-related mortality has declined due to a reduction in the prevalence of rheumatic heart disease. Changes in clinical practice that stand out were the aggressive control of the hypertensive component of toxemia leading to a reduced incidence of intracranial hemorrhage, the prompt recourse to blood transfusion for hemorrhage, and the use of broad spectrum antibiotics.

Female↗

Need for better severity indexes of acute myocardial infarction under diagnosis-related groups.

Clinical, demographic and administrative data, including length of stay and institutional charges, were examined for 219 patients hospitalized for acute myocardial infarction (AMI). Neither length of stay nor charges differed among AMI patients with or without cardiovascular complications as defined by Medicare's diagnosis-related group (DRG) categories (DRG 121 and 122, respectively) for patients who are discharged alive. Myocardial enzyme peak levels are the best predictors of hospital resource consumption for patients with AMI when considered alone or in combination with other factors. The "cardiovascular complications" designated by discharge diagnoses did not reflect resource consumption in our patient population. Sixteen percent of the patients studied underwent cardiac catheterization during hospitalization. These patients stayed in the hospital longer and incurred 70% higher charges; nevertheless, they were grouped with the remaining AMI patients in the current DRG formulation. Clinical evaluations such as cardiovascular complications are subject to interpretation, and are therefore less credible than enzyme measurements for recognizing the severity of a patient's AMI. Reimbursement based on objective measurements may avoid payment inequities.

Aged↗

Maternal mortality in Massachusetts. Trends and prevention.

To identify ways in which the safety of childbirth might be increased, we investigated the causes of death among the 886 women who died during pregnancy or within 90 days post partum ("maternal deaths") in Massachusetts from 1954 through 1985. The maternal mortality rate declined from 50 per 100,000 live births in the early 1950s to the current rate of 10 per 100,000 live births. Between one third and one half of the maternal deaths were considered to have been preventable. The leading causes of maternal death from 1954 through 1957 were infection, cardiac disease, pregnancy-induced hypertension, and hemorrhage. In contrast, from 1982 through 1985 the leading causes of death were trauma (suicide, homicide, and motor vehicle accidents) and pulmonary embolus. We observed a rapid increase in the frequency of death among women who received little or no antenatal care. From 1980 through 1984 the maternal mortality rate for white women was 9.6 per 100,000 live births, whereas for nonwhites it was 35 per 100,000 live births (relative risk, 2.9; 95 percent confidence limits, 2.5 and 3.2). Fifty percent of the nonwhite women who died during pregnancy or within 90 days post partum received little or no antenatal care, in contrast to only 15 percent of the white women. These data show that the leading causes of maternal death have changed markedly in Massachusetts during the past 30 years. Although the overall maternal mortality rate has declined sharply, further improvement may occur with better antenatal care and specific efforts to prevent trauma and pulmonary embolus.

Cesarean Section↗

Effects of positional changes on inferior vena caval size and dynamics and correlations with right-sided cardiac pressure.

Effects of supine and lateral positions on the size and shape of the inferior vena cava (IVC) were studied in 30 normal persons and in 53 patients with cardiac disease undergoing right-sided cardiac catheterization. In normal subjects, mean values for both IVC diameter and area decreased significantly (p less than 0.01) from the right lateral (22 +/- 3 mm and 3.9 +/- 0.6 cm2, respectively) to the supine position (15 +/- 5 mm; 1.8 +/- 0.9 cm2) to the left lateral position (7 +/- 3 mm; 0.8 +/- 0.4 cm2). IVC shape was round in the right lateral, oval in the supine, and slit-like in left lateral position. In the 53 patients, significant differences in IVC diameter and area were also detected in all 3 positions. However, when separated into 2 groups according to right atrial pressure, patients with normal pressure (8 mm Hg or less) had diameter and area values equivalent to those of normal subjects, whereas patients with elevated right atrial pressure (more than 8 mm Hg) had supine and left lateral IVC diameters and areas that were larger than normal, and approximately equivalent: diameters--23 +/- 3 mm (right), 18 +/- 5 mm (supine) and 17 +/- 7 mm (left); areas--4.1 +/- 0.8 cm2 (right), 3.3 +/- 1.2 cm2 (supine) and 3.1 +/- 1.3 cm2 (left). IVC diameters and areas in all 3 positions correlated with mean right atrial pressure, measured subsequently in the supine position, but the left lateral position provided the strongest correlations (r = 0.85, IVC diameter vs right atrial pressure; r = 0.89, IVC area vs right atrial pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Associations of handedness with hair color and learning disabilities.

Forms containing the Edinburgh handedness inventory and questions about learning disabilities, hair color, self-described handedness, age, gender, parental handedness and twinning were received from 1117 randomly selected professionals. Laterality scores (LS, range -100 to +100) were calculated for each respondent based on the handedness inventory and were correlated with the above variables. Among blonds, the frequency of non right-handedness (NRH, LS less than or equal to 70) was 44% compared to 24% of non-blonds (chi 2 = 23.5, P less than 0.0001). Learning disabilities (LD) were present in 9% of NRH (LS less than or equal to 70) as against 3% of those with LS greater than 70 (chi 2 = 22.1, P less than 0.0001). Associations between LS and self-described handedness, parental handedness, gender, and age are also presented. Possible explanations for the association of hair color and handedness are discussed in light of recent data on altered visual system pathways in albinos. Problems in the measurement of handedness are discussed.

Adult↗

The normal parturient's admission temperature.

The relationship between oral temperature taken at the time of admission and the duration of elapsed labor was evaluated. Onset of labor data revealed a diurnal distribution with an apogee at midnight to 2 AM and a nadir at 11 AM to noon. Temperature data ranged from 94.3 degrees to 99.7 degrees F (34.6 degrees to 37.6 degrees C). The mean temperature of 97.8 degrees +/- 0.8 degrees F (36.6 degrees +/- 0.44 degrees C) is significantly lower (p less than 0.001) than the clinical reference temperature of 98.6 degrees F (37.0 degrees C). A likely explanation is the coincidental admission time (early to late morning) and the nadir of the diurnal variation in temperature. Linear regression fitted to the data (after deletion of six hypothermic outliers) yielded the relationship: temperature = 97.8 degrees F + 0.0115 X duration of elapsed labor (temperature = 36.6 degrees C + 0.0064 X duration of elapsed labor) for which the correlation coefficient is not statistically significant.

Body Temperature↗

Failure of hypnotic suggestion to alter immune response to delayed-type hypersensitivity antigens.

The ability to alter delayed-type hypersensitivity via hypnotic suggestion was tested in 12 highly hypnotizable, untrained subjects and 30 nonhypnotized controls. Subjects were skin-tested bilaterally with a standardized panel of delayed hypersensitivity antigens and instructed either to enhance or suppress the skin test response unilaterally. Compared with results in controls, the skin test response reflected no effect of hypnotic suggestion with regard to either the area of induration or the degree of inflammation assessed histologically.

Adult↗

Hepatic disposition and biliary excretion of bilirubin and bilirubin glucuronides in intact rats. Differential processing of pigments derived from intra- and extrahepatic sources.

Mechanisms for transport of bilirubin and its conjugates in hepatocytes have not been defined. We investigated the hepatic processing of bilirubin glucuronides and their precursors, and characterized the disposition of bile pigments arising from intraversus extrahepatic sources. Tracer doses of purified radiolabeled biliverdin, bilirubin, bilirubin monoglucuronide (BMG) or diglucuronide (BDG) were administered intravenously to intact normal or jaundiced homozygous Gunn rats. Rapid sequential analysis of radiolabeled BMG and BDG in bile revealed comparable excretion patterns following biliverdin and bilirubin injection, with BDG as the major pigment. Biliary excretion of radiolabeled conjugates from injected BMG was more rapid, with BMG predominating. Excretion of injected BDG in normal rats and BMG or BDG in Gunn rats was virtually identical to that of unaltered BMG in normal rats. Model independent analysis by deconvolution provided objective comparison of the disposition of radiolabeled pigments from the different sources. These findings indicate that bilirubin glucuronides formed in the liver from endogenous (hepatic) and exogenous (extrahepatic) sources of bilirubin follow a similar excretory pathway. BMG formed endogenously is converted preferentially to BDG, whereas circulating BMG is excreted predominantly unchanged. Exogenous conjugated bilirubins are excreted more rapidly than those generated intrahepatically, by a transcellular pathway that is largely independent of the conjugation system.

Animals↗

Ultrasonography for fetal weight estimation: the Birnholz equation.

In the population of 563 normal live births, subject to the selection criteria of this study, the mean ultrasonographically-estimated fetal weight calculated using the Birnholz equation accurately predicts the mean true birth weight with less than 1 percent error. However, on a pairwise basis, the error was found to be systematic (rather than random) with a large standard error of the estimate (+/- 300 g). The equation consistently underestimated the mean birth weight between 1500-3750 g and consistently overestimated it thereafter.

Birth Weight↗