Biomedical subjects
R Cooper
Publications and source records attributed to R Cooper.
Pleomorphic lipoma--a case report.
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Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro.
Parvovirus B19 infection leads to transient aplastic crises in individuals with chronic hemolytic anemias or immunodeficiency states. An additional unexplained sequela of B19 infection is thrombocytopenia. Because B19 is known to have a remarkable tropism for human erythropoietic elements, and is not known to replicate in nonerythroid cells, the etiology of this thrombocytopenia is uncertain. We sought to define the pathobiology of B19-associated thrombocytopenia by examining the role of B19 on in vitro megakaryocytopoiesis. B19 infection of normal human bone marrow cells significantly suppressed megakaryocyte (MK) colony formation compared with mock-infected cells. No such inhibition was observed with a nonpathogenic human parvovirus, the adeno-associated virus 2 (AAV). The B19-MK cell interaction was also studied at the molecular level. Whereas low-density bone marrow cells containing erythroid precursor cells supported B19 DNA replication, no viral DNA replication was observed in B19-infected MK-enriched fractions as determined by the presence of viral DNA replicative intermediates on Southern blots. However, analysis of total cytoplasmic RNA isolated from B19-infected MK fractions showed a low-level expression of the B19 genome as detected by quantitative RNA dot blots as well as by Northern analysis. Furthermore, a frame-shift mutation in a recombinant AAV-B19 hybrid genome segment that encodes the viral nonstructural (NS1) protein significantly reduced the observed inhibition of MK colony formation. These studies indicate tissue-tropism of B19 beyond the erythroid progenitor cell, and lend support to the hypothesis that B19 genome expression may be toxic to cell populations that are nonpermissive for viral DNA replication.
Characterization of peptidyl-nucleoside antifungal antibiotics from fermentation broth.
Characterization of sinefungin related antifungal antibiotics from fermentation broth was accomplished by coupling photodiode array (PDA) detection to high performance liquid chromatography (HPLC). From the combined HPLC-PDA evaluation of broth filtrate, we detected five sinefungin related components. Fast atom bombardment (FAB) mass spectroscopic evaluations, mass-analysed ion kinetic energy spectra (MIKES) and collision activated (CA) MIKES of these components confirmed their respective identities. Our findings from the combination of HPLC photodiode array acquisition and FAB-mass spectrometry suggest we have detected the presence of a previously unreported sinefungin analogue.
Single papillary muscle and ostium primum defect.
Parachute mitral valve (single papillary muscle) is commonly associated with complete atrioventricular (AV) canal. We report a case of ostium primum defect associated with single papillary muscle.
Changes of slow and steady brain potentials during complex tasks.
Recordings of slow potentials and changes of steady level of the EEG in man during manual and mental tasks show that an increase in mental load (as determined by the difficulty of the task) is accompanied by an increase in negativity at midline electrodes. It is suggested that this negativity is due to cortical excitation that facilitates performance.
Carbendazim-induced alterations of reproductive development and function in the rat and hamster.
We are developing a data base that will allow us to select endpoints that would be useful in the detection of reproductive toxicity in a multigenerational test. In this effort, carbendazim (MBC), a known reproductive toxicant, was administered to male and female rats from weaning, through puberty, gestation, and lactation. A similar study was conducted with hamsters. In rats, MBC was administered at 0, 50, 100, 200, or 400 mg/kg/day. Hamsters were dosed at 0 or 400 mg/kg/day. In the parent (P0) generation, landmarks of puberty were measured. In females, estrous cyclicity, litter size, the number of implants, organ weights, and histology were assessed. Our assessment of the male rat included organ weights, testicular and epididymal sperm counts, a quantitative measure of sperm motility, sperm morphology, testicular histology, and endocrine measures. The growth, viability, and reproductive function of the offspring (F1) were observed during a 4-month period of continuous breeding. In the P0 of both species. MBC did not alter pubertal development, growth, or viability. The reproductive potential of the rats treated with MBC at 200 and 400 mg/kg/day was reduced due to effects on sperm production and fetal viability. In the male rat, MBC treatment markedly altered sperm morphology, testicular and epididymal weights, and sperm numbers and testicular histology. Fertility, sperm motility, and hormonal levels were altered, primarily in the males with very low sperm counts. The ability to conceive did not appear to involve a female factor. In P0 female rats, MBC administration caused postimplantation losses in the high-dosage groups and a few malformed rat pups were found in the litters from the 100 and 200 treatment groups. MBC was less toxic to the hamster than the rat. The only reproductive effects induced by MBC treatment were on sperm measures. Fertility of the P0 generation and fetal and neonatal (F1) viability were not decreased by MBC administration. In the male rat, testis weight, sperm numbers in the cauda epididymis and testis and sperm morphology were sensitive to the effects of MBC. In females, counting implantation scars at necropsy was useful, as this information allowed us to confirm pregnancy and identify postimplantation losses induced by MBC administration.
Survival determinants in black patients with angiographically defined coronary artery disease.
Long-term survival of blacks with angiographically defined coronary artery disease was examined in a series of 1233 consecutive patients who underwent cardiac catheterization at a large urban municipal hospital. Vital status information was available at a mean of 86 weeks for the cohort as a whole, and 94 deaths were recorded. As noted in other angiographic series that included blacks, a high proportion of patients in this study had unobstructed coronary arteries (41%), and there was a preponderance of women (56%). Hypertension was present in 82% of the cases, whereas 68% of the sample had left ventricular hypertrophy as revealed by echocardiogram. The cumulative proportion of patients who were surviving at 5 years was 90 +/- 1 (+/- SEM), 79 +/- 4, and 70 +/- 4 for patients with no obstructive lesions, one-vessel disease, and multivessel disease, respectively. The survival rate at 3 years for patients who had undergone bypass surgery (N = 152) was only 82% (+/- 5%). Noninvasive univariate predictors of mortality included male sex, history of myocardial infarction, Q waves on electrocardiogram, exercise duration on treadmill stress testing, and left ventricular hypertrophy. Angiographic predictors included left ventricular end-diastolic pressure, the number of diseased coronary vessels, ejection fraction, and mean pulmonary artery pressure. Regression analysis showed an independent association for all the angiographic variables noted previously as well as for echocardiographically determined left ventricular hypertrophy. Survival rates for blacks with coronary artery disease in this series were considerably lower than those currently reported for whites, particularly for patients who underwent coronary bypass grafting.(ABSTRACT TRUNCATED AT 250 WORDS)
Correlation of electroencephalogram, respiration and movement in the Rett syndrome.
Day time video records of 14 girls with the Rett syndrome (RS) (6-17, mean 7 years) were analysed to correlate episodic abnormalities in respiration, movement and electroencephalograms (EEG). Records were compared with those of 12 healthy girls (6-18, median 14 years) who hyperventilated voluntarily. Three RS girls (6-7 years) had minimal respiratory dysrhythmia and showed no correlation between EEG respiration and movement. The other 11 RS girls (6-17 years) had severe awake respiratory dysrhythmia; 10 showing hyperventilation (with hypocapnia) which alternated with active expiratory apnoeic pauses and one with the latter only. All had periods of awake regular breathing with normal respiratory gases. In these girls EEG showed non-epileptic generalised slow activity some of which was paroxysmal. In the six youngest (6-10 years) of these 11 RS girls, non-epileptic paroxysms of EEG slow activity at 1 1/2-4 Hz occurred and were associated with periods of normal breathing and normal pCO2 levels whether girls were alert, drowsy or asleep, but were uncommon during episodes of hyperventilation (and hypocapnia). In four of these girls the EEG paroxysms occupied less than or equal to 1-3% of the time during periods of respiratory dysrhythmia (81 minutes) and 8-100% of the time during alert periods with normal breathing (29 minutes), p less than or equal to 0.001 for this difference. Short bursts of EEG slowing occasionally followed prolonged apnoeic pauses. In two cases brief partial complex seizures occurred. In five of these girls stereotypic movements exacerbated during episodes of respiratory dysrhythmia and reduced during normal breathing.(ABSTRACT TRUNCATED AT 250 WORDS)
The nature of pre-operative anxiety.
In a study of 247 patients who had general anaesthesia for dental procedures, the incidence of individual anxieties was noted using a questionnaire completed by the patient. The most common anxieties related to the period before transfer to the operating theatre, intra-operative awareness and postoperative pain. These anxieties were present in over half the patients questioned. The follow-up questionnaire was completed by 207 patients in order to indicate which anxieties they would expect to have if they needed anaesthesia in the future. All anxieties were less frequent than found before operation.
Haemobilia--diagnosis by 99Tcm labelled red blood cell scintigraphy.
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Slowdown in the decline of stroke mortality in the United States, 1978-1986.
The gradual decline in stroke mortality rates observed in the United States since 1900 accelerated markedly around 1973 for whites and around 1968 for blacks. During the next decade stroke mortality rates decreased by almost 50% so that the United States now experiences one of the lowest stroke mortality rates in the world. Beginning in 1979, however the annual rate of decline in stroke mortality began to slow considerably. Comparing the period 1979-1986 with the previous decade, a 57% slowing in the absolute rate of decline (as estimated by the slope of the linear portion of the mortality curve) was observed for white men; the corresponding slowdowns in the rate of decline were 58% for white women, 44% for black men, and 62% for black women. If the decline during the 1980s had continued at the rate observed for the period 1968/73-1978, there would have been 131,000 fewer stroke deaths during the period 1979-1986, 28,000 fewer in 1986 alone. This slowdown in the rate of decline in stroke mortality is occurring while mortality rates for both coronary heart disease and all causes are leveling off. The reasons for this change in the mortality trend remain unknown, and corresponding trends in the treatment and control of hypertension do not provide an entirely satisfactory explanation.
Saramycetin, a thiazolyl peptide from a Streptomyces sp.: chemical characterization and molecular weight determination.
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Labetalol in the control of cardiovascular responses to electroconvulsive therapy in high-risk depressed medical patients.
Labetalol, a drug with alpha- and beta-adrenergic receptor blocking effects, was used to attenuate hypertension and tachycardia associated with electroconvulsive therapy (ECT) in a series of 11 elderly patients with refractory depression and cardiovascular disease in a placebo-controlled, double-blind crossover study design. As compared with placebo, labetalol was found to blunt mean arterial pressure (MAP) increase by up to 8.26% (p less than .001), heart rate increased by up to 26.07% (p less than .001), frequency of atrial arrhythmias by up to 100% (p less than .01), and premature ventricular contractions by 41.97%. No untoward side effects were observed, and no effect on treatment outcome was noted. Labetalol appears to be an effective and safe agent to use in decreasing hypertension, tachycardia, and possibly arrhythmias in high-risk medical patients with cardiovascular disease undergoing ECT.
Trends in hospitalization rates for heart failure in the United States, 1973-1986. Evidence for increasing population prevalence.
Discharge data from a representative sample of short-stay US hospitals were examined to obtain information regarding trends in the prevalence of congestive heart failure from 1973 through 1986. During this 14-year period, the number of discharges more than doubled and the age-adjusted rates increased from 53% to 88% among the four major sex-race groups. On average, nonwhite men experienced annual hospitalization rates 33% higher than white men, while for women the corresponding nonwhite rates were 50% higher. Hospitalization rates during this period remained constant for persons younger than 55 years but rose sharply in the elderly. Concurrently, a slight decline in case fatality rates for an individual hospitalization was seen. The two factors accounting for the growing prevalence of congestive heart failure seem to be the increasing average age of the population and the longer survival of persons with chronic heart disease. The role of improved medical therapy during the period of this study remains uncertain. Increasing demands to provide care for the congestive heart failure syndrome are likely to continue in the coming years, and medical facilities should develop new intervention strategies to treat or prevent the underlying conditions leading to heart failure as well as decrease the need for hospitalization in this common disorder.
Severity of coronary artery disease among blacks with acute myocardial infarction.
A growing body of evidence suggests that survival after acute myocardial infarction (AMI) is considerably worse among blacks than whites. The severity of coronary artery disease (CAD), as measured by the number of diseased vessels and the degree of left ventricular dysfunction, is the major determinant of survival after AMI. To determine whether or not the severity of CAD could explain the poor prognosis in a cohort of blacks followed at this institution, cardiac catheterization was performed in a consecutive series of 51 patients less than 70 years of age. All patients were studied within 2 weeks after AMI. The mean age of the patients was 56 +/- 8 (mean +/- standard deviation) and 71% were men. A greater than or equal to 50 narrowing in 0, 1, 2 or 3 coronary arteries was noted in 5, 24, 40 and 31%, respectively. Left main stenosis was present in 3 patients (6%) and the mean left ventricular ejection fraction was 55%. In a subgroup of 20 patients echocardiographic estimates of left ventricular mass/height yielded a mean of 196 g/m, and left ventricular hypertrophy on echocardiogram was present in 74%. These data indicate that among blacks with AMI in this series CAD was only modestly more severe than expected and suggest that other factors most likely explain the high mortality in blacks after hospital discharge.
Microtubule depolymerization inhibits the regulation of alpha 1-acid glycoprotein mRNA by hepatocyte stimulating factor.
Hepatocyte stimulating factor (HSF, a polypeptide cytokine) is a major regulatory hormone responsible for hepatic acute-phase reactant (APR) induction following acute systemic injury. The mechanisms by which HSF regulates APR synthesis in the liver are unknown. Microtubules are involved in a number of polypeptide hormone-mediated events which can be modified, either positively or negatively, by microtubule depolymerizing agents. In this study we have used colchicine (a microtubule depolymerizing drug) to assess whether or not HSF-mediated changes in rat hepatic alpha 1-acid glycoprotein (AGP) or albumin mRNA levels require an intact microtubule cytoskeletal system. Cultured rat hepatocytes were pretreated for 30 min with either colchicine (10(-6) M), or the inactive isomer lumicolchicine (10(-6) M), or fresh medium. Following pretreatment, purified murine macrophage HSF (10 units/ml) was added and the cells were incubated for an additional 12 h. Colchicine, but not lumicolchicine, significantly inhibited the HSF-dependent regulation of mRNA for the positive APR, AGP, but had no effect on the mRNA levels of albumin, a negative APR. Furthermore, removal of colchicine from previously inhibited cultures allowed HSF to restimulate AGP mRNA expression. These data suggest that microtubules may play a regulatory role in controlling the expression of the genes for positive acute-phase proteins and may explain the temporal differences found in vivo between positive and negative APR expression.
Pulmonary function in preterm infants following treatment with intravenous indomethacin.
Pulmonary function tests, including measurements of arterial blood gas levels, total pulmonary compliance, and arterial-alveolar oxygen ratios, were performed in 38 ventilator-dependent preterm infants with respiratory distress syndrome who weighed less than 1500 g at birth. Twenty-seven had a physiologically significant patent ductus arteriosus (PDA). Twelve were assigned at random to receive three doses of intravenous indomethacin, 0.2 mg/kg per dose, on the fourth day of life. This treatment resulted in ductal closure in seven infants by the seventh day of life. Another concurrently observed group of 15 infants with PDA received no indomethacin. A third group of 11 infants lacked evidence of a PDA. Pulmonary function in the infants who received indomethacin did not differ significantly from that in the other two groups.