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Biomedical subjects

R D White

Publications and source records attributed to R D White.

At least 181 records · Page 10Linked to original sources
PubMed1986

Effect of CO2, calcium, digoxin, and potassium on cardiac and skeletal muscle metabolism in malignant hyperthermia susceptible swine.

The effects on whole body or cardiac metabolism of carbon dioxide, calcium, potassium, or digoxin were studied in 16 normal swine and 31 swine susceptible to malignant hyperthermia (MHS). Malignant hyperthermia (MH) was defined as an increase in metabolism that occurred in MHS but not in normal pigs. Whole body response: despite a sustained PaCO2 greater than 130 mmHg, MH did not develop in four intact MHS swine during thiopental-N2O anesthesia and controlled ventilation. Drugs given during total cardiopulmonary bypass: MH did not develop in five MHS pigs with blood ionized calcium to 15 mEq/l, in four MHS pigs with digoxin levels to 60 ng/ml, or in four normal pigs with potassium to 10 mEq/l. In six MHS pigs, oxygen consumption increased from 6.5 to 11.6 ml O2 X min-1 X kg-1 when potassium exceeded 6 mEq/l; lactate did not increase. Cardiac response (during extracorporeal right heart bypass): eight pigs (four normal, four MHS) with blood ionized calcium to 5 mEq/l and eight pigs (four normal, four MHS) with digoxin levels above 7.5 ng/ml had increased myocardial oxygen consumption. Cardiac potassium efflux or lactate production did not occur in normal or MHS pigs. Increased arterial potassium (7.4-8.5 mEq/l) did not alter myocardial oxygen consumption or lactate production in four MHS or four normal pigs. MH responses were initiated only by potassium and only in regard to whole body metabolism. Cardiac metabolism increased as a result of specific drugs (calcium, digoxin), unrelated to MH phenomena. Porcine inbreeding resulting in MH susceptibility of skeletal muscle does not imply abnormality in other tissues.

Animals↗
PubMed1986

Foreign body airway obstruction: considerations in 1985.

Management of foreign body airway obstruction continues to be a major controversy in emergency medical care. Much of the disagreement is without doubt based on lack of a uniformly accepted model of acute airway obstruction representative of the clinical event. A variety of models have been used to assess different aspects of airway obstruction by foreign bodies. These models have analyzed, among other variables, kinetic energy and inertial and aerodynamic forces in attempts to focus on specific aspects of this controversy. Human volunteers, anesthetized and paralyzed patients, and cadavers have also been used. In several recent studies it was concluded that subdiaphragmatic pressure is the treatment of choice, while in at least one additional study firm back blows applied with the patient's head hanging downward were recommended as the treatment most likely to relieve airway obstruction. It seems likely that these apparently conflicting views can be reconciled and that a consensus recommendation for treatment of this emergency can be effected.

Airway Obstruction↗
PubMed1985

Equilibrium denaturation of pituitary- and recombinant-derived bovine growth hormone.

Holladay and co-workers [Holladay, L. A., Hammonds, R. G., & Puett, D. (1974) Biochemistry 13, 1653-1661] reported the presence of an equilibrium intermediate in the guanidine hydrochloride (GdnHCl) induced denaturation of pituitary-derived bovine growth hormone (p-bGH). Since then, numerous reports have appeared demonstrating the inherent heterogeneity in p-bGH. In this report we show that a standard preparation of p-bGH can be separated into two components of almost equal abundance differing in molecular weight by approximately 1000. Each of these two components could give rise to different denaturation transitions which would be interpreted as evidence for equilibrium intermediates. We report here the equilibrium denaturation of bGH produced by Escherichia coli through recombinant DNA technology. The recombinant-derived bGH (r-bGH) is more homogeneous than that derived from pituitary sources and is greater than 95% a single polypeptide entity. Nevertheless, the GdnHCl-induced denaturation profiles of both recombinant bGH and pituitary bGH are very similar. The presence of equilibrium intermediates is verified by the asymmetry of the denaturation transition as measured by size-exclusion high-performance liquid chromatography and by noncoincidence of the denaturation transitions as observed by ultraviolet absorbance, fluorescence intensity, and circular dichroism. These findings conclusively show that the secondary structure of bovine growth hormone is more stable than the tertiary structure and is consistent with a framework model of protein folding.

Animals↗
PubMed1985

Diagnostic and prognostic significance of minimally elevated creatine kinase-MB in suspected acute myocardial infarction.

CK-MB changes were studied using agarose gel electrophoresis in 244 patients admitted to a coronary care unit for suspected acute myocardial infarction (AMI). A range of minimally elevated CK-MB levels, from 1 to 24 IU/liter, was identified as representing uncertain AMI events. Positive AMI events were defined by elevations of 25 IU/liter or more documented in patients with new Q waves or abnormalities in all enzyme and isoenzyme levels. Negative AMI events were defined by elevation of 0 IU/liter, observed in all control subjects. The 1-year cardiac mortality rates in the "positive"-AMI (n = 91) and "uncertain"-AMI (n = 22) groups were identical (22%), and significantly higher than that in the "negative"-AMI group (n = 93) (6%) (p less than 0.05). However, when a larger uncertain-AMI group of 115 patients was compiled by 2 collaborating centers, the 1-year cardiac mortality rate in the 39 patients with chest pain alone was 0%, vs 33% in the 76 patients with accompanying severe medical problems such as cardiac or respiratory failure. Whether minimal CK-MB elevations represent AMI of limited extent is not clear. These elevations occur most often in association with severe medical problems, and in patients without such problems, they may not indicate a poor prognosis.

Adult↗
PubMed1985

Evaluation of a QRS scoring system for estimating myocardial infarct size. V. Specificity and method of application of the complete system.

The specificity of a previously developed 57-criteria/32-point QRS scoring system for estimating myocardial infarct (MI) size is evaluated in an extensive control population and the method of application of this system for determining a QRS score from a standard 12-lead electrocardiogram is described. Points are accumulated from Q- and R-wave durations, R- and S-wave amplitudes, R/Q- or R/S-amplitude ratios and the presence of R-wave notching, with each point representing approximately 3% of the left ventricle. The subjects were selected because of the minimal likelihood of their having had myocardial infarcts or other sources of QRS modification. There were 500 consecutively selected normal Caucasian subjects, aged 20 to 69 years, with 50 women and 50 men in each of the 5 decades. Specificity for the 57 individual criteria ranged from 89 to 100%. Fifty-one criteria met the required standard of at least 95% specificity; of the 6 that failed, 3 were successfully modified to achieve this standard and 3 were eliminated. In the resultant 54-criteria/32-point complete system, the total population, as well as both women and men, required more than 3 points to attain at least 95% specificity. Subjects in each of the 5 decades met the specificity standard either at or below the level of more than 3 points. The point score at which 95% or greater specificity was attained for the 10 age/sex subsets varied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Varicocele: temporal considerations.

The pathophysiology of the abnormal spermatogenesis seen in the presence of the varicocele has not been elucidated in spite of extensive study. Furthermore, no satisfactory explanation exists for the bilateral abnormal spermatogenesis seen in a process which is felt to be unilateral in the majority of cases. The present study was designed to determine if a surgically produced unilateral varicocele would lead to ipsilateral testicular changes prior to the onset of contralateral testicular alterations. Utilizing the rat model and microsurgical techniques, the effects of the varicocele on ipsilateral and contralateral spermatogenesis was studied at intervals over 49 days. Mean seminiferous tubular diameter measurements and flow cytometric analysis of testicular tissue were utilized to assess spermatogenesis. A statistically significant decrease in mean seminiferous tubular diameter was seen between day 1 and day 49 in the left testicle. The right testicle tended to demonstrate similar changes but these were not significant by the method of analysis used. Flow cytometric analysis of testis DNA content also revealed a statistically significant difference in the percentage of haploid, diploid and tetraploid cells in the left testis on day 1 as compared to day 49. The right testis again tended to demonstrate similar but not significant changes. Though primarily a unilateral process, bilateral spermatic vein abnormalities were also visualized in some animals. This observation may contribute to the bilateral effect observed. These studies demonstrate that a surgically created left varicocele will result in bilateral testicular alterations. Within the time frame of the study, the ipsilateral alterations progressed to a greater degree.

Animals↗
PubMed1985

The effects in volunteers of BW12C, a compound designed to left-shift the blood-oxygen saturation curve.

BW12C, a potent left-shifting anti-sickling compound in vitro, was administered to normal healthy male Caucasian volunteers. Doses of 2-20 mg kg-1 given by intravenous infusion over 1 h caused a dose-dependent left-shift of the blood-oxygen saturation curve and at the highest dose some 16% of the haemoglobin existed in a high affinity form. Peak left-shift was observed at the end of infusion and decayed thereafter with a mean half-life of approximately 3 h. There were no adverse systemic effects, either clinical, biochemical or haematological, but there was some local irritation at the intravenous infusion site if the infusion was too concentrated. Pharmacokinetic measurements indicated uptake into erythrocytes, low levels in plasma and a volume of distribution not appreciably greater than the blood volume. A pilot radiolabel study indicated extensive metabolism with elimination into the urine.

Adult↗
PubMed1985

Relationship between thiol depletion and chemosensitization in a transplantable murine bladder tumor.

The effect of pretreating the C3H/He mouse MBT-2 tumor with diethyl maleate (DEM), buthionine-S R-sulfoximine (BSO), or misonidazole (MISO) before administration of cyclophosphamide (CTX) was studied with the use of tumor volume-doubling time delay as an endpoint. The kinetics of glutathione (GSH) depletion and regeneration in the tumor and in the host liver were determined after treatment with the thiol-depleting agents. CTX was administered at appropriate time points. MISO was the most effective chemosensitizer at a time point at which tumor GSH content was 80-85% of the control value. Both BSO and DEM were chemosensitizers in relation to the degree they had reduced tumor GSH levels. This chemosensitization was significant at 50% GSH reduction. By combining MISO and BSO at doses lower than previously used for each agent alone, highly effective sensitization of subsequent CTX was obtained.

Animals↗
PubMed1985

Surgical management of Stage B or C prostatic carcinoma: radical surgery vs radiotherapy.

Radical prostatectomy provides an excellent degree of disease control for the longest period of time in patients with localized prostatic cancer. Although advocates of radiation therapy point to nearly identical survival curves for patients treated with either interstitial or external techniques, an analysis of disease-free survival suggests that radical prostatectomy yields the best long-term "cure." Crude fifteen-year survival rates of 50 per cent may be achieved with radical prostatectomy, compared with 20 per cent to 25 per cent associated with radiation therapy. Additional experience with long-term survival data is necessary before a final conclusion can be drawn from comparison of the two treatment modalities.

Brachytherapy↗
PubMed1984

Evaluation of a QRS scoring system for estimating myocardial infarct size. IV. Correlation with quantitative anatomic findings for posterolateral infarcts.

This study correlated the location and size of posterolateral myocardial infarcts (MIs) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral MIs and no confounding factors of ventricular hypertrophy or bundle branch block in their ECG. Left ventricular anatomic MI size ranged from 1 to 46%. No patient had a greater than or equal to 0.04-second Q wave in any electrocardiographic lead and only 55% had a 0.03-second Q wave. A 29-point, simplified QRS scoring system consisting of 37 weighted criteria was applied to the ECG. Points were scored by the ECG in 85% of the patients (range 1 to 8 points). MI was indicated by a wide variety of QRS criteria; 19 of the 37 criteria from 8 different electrocardiographic leads were met. The correlation coefficient between MI size measured anatomically and that estimated by the QRS score was 0.72. Each point represented approximately 4% MI of the left ventricular wall.

Adult↗
PubMed1984

The bioactivation of 1,2-dibromoethane in rat hepatocytes: deuterium isotope effect.

The metabolism and genotoxicity of 1,2-dibromoethane (EDB) and its deuterium substituted analog ( d4EDB ) were studied in isolated rat hepatocytes. There was a marked isotope effect on the metabolism of EDB by hepatocytes. This was due to decreased microsomal oxidation of d4EDB . Cytosolic metabolism of EDB, as measured by bromide ion release, was unaffected by deuterium substitution. The genotoxicity of the two analogs was assessed by assaying for the presence of EDB induced single-strand breaks in DNA. As measured by the alkaline elution technique, both compounds caused DNA single-strand breaks when incubated at a concentration of 0.1 mM with hepatocytes. No difference in the degree of DNA damage could be demonstrated between hepatocytes incubated with EDB or d4EDB . These data suggest that the GSH transferase mediated metabolism of EDB is responsible for the genotoxic effects of EDB observed in hepatocytes.

Animals↗
PubMed1984

Studies of lesions induced in the testis and epididymis of F-344 rats by inhaled methyl chloride.

Experiments were carried out in rats to characterize the development of the testicular and epididymal lesions and any associated effects on reproductive hormones. Adult F-344 rats were exposed to 3500 ppm methyl chloride (MeCl) 6 hr/day for 5 days, not exposed for 3 days, and exposed again for 4 days. The first consistent testicular lesion was a delay in spermiation which appeared on Day 9. Subsequently, germinal epithelial vacuolation and cellular exfoliation became widespread as exposure continued. All animals killed after 19 days also displayed bilateral epididymal granulomas in regions 5 or 6 of the cauda epididymis. The nature and distribution of inflammatory cells indicated that the primary neutrophilic response may be against the tubular epithelium and not extravasated sperm. After 5 days of exposure, circulating testosterone was below 6 ng/ml (control: 120 +/- 31 ng/ml). Both MeCl exposed and control animals responded similarly to challenge with hCG and LHRH ethylamide, suggesting that Leydig cell and gonadotrope function was unaffected. It is proposed that MeCl acts centrally to lower circulating testosterone. Nonprotein sulfhydryls were depleted in liver, testis, and epididymis after MeCl exposure, but not in whole blood. This finding indicates that sulfhydryl depletion is not due to direct alkylation, but is enzymatically mediated. Sulfhydryl depletion did not correlate with lesion development. It was concluded that the initial testicular effects of MeCl are directed at either the late stage spermatids or the Sertoli cells with a resultant delay in spermiation.

Animals↗
PubMed1984

The effect of buthionine sulfoximine, an inhibitor of glutathione synthesis, on hepatic drug metabolism in the male mouse.

Buthionine sulfoximine significantly reduced the hepatic non-protein sulfhydryl (NPSH) content of male B6C3F1 mice within 2 h after intraperitoneal (i.p.) injection. This treatment did not affect the activity of several hepatic microsomal and cytosolic enzymes responsible for xenobiotic metabolism. Pretreatment of mice with buthionine sulfoximine (2 mmol/kg) increased the hepatotoxicity of chloroform, but did not affect the hepatotoxicity of carbon tetrachloride. These findings suggest that buthionine sulfoximine can be a useful agent for studying the role of glutathione (GSH) in hepatic biotransformation of xenobiotics.

Animals↗
PubMed1984

Hemodynamic effects of calcium chloride injection following cardiopulmonary bypass: response to bolus injection and continuous infusion.

To determine the hemodynamic effects of intravenous injection of calcium chloride, 26 patients were studied immediately after termination of extracorporeal circulation. Eighteen patients (Group A) had injection of a single bolus of CaCl2; in the other 8 patients (Group B), the bolus injection was followed by infusion of CaCl2 at a rate of 1.5 mg/kg/min for 10 minutes. Myocardial contractile element velocity (Vpm), aortic blood flow, electrocardiograms, and left ventricular, systemic arterial, pulmonary arterial, and left atrial pressures were recorded continuously. The baseline ionized calcium level after bypass was 3.6 +/- 0.6 mg/100 ml (normal range, 3.9 to 4.5 mg/100 ml); this increased to 5.4 +/- 0.5 mg/100 ml 1 minute after CaCl2 injection. The ionized calcium level was 4.7 +/- 0.6 mg/100 ml 6 minutes after CaCl2 injection in Group A, and was 5.9 +/- 0.2 mg/100 ml and 6.4 +/- 0.2 mg/100 ml at 6 and 10 minutes, respectively, in Group B. There was significant early hemodynamic improvement after CaCl2 injection, including increases in Vpm (p less than 0.001), cardiac index (p less than 0.001), mean blood pressure (p less than 0.01), and stroke volume index (p less than 0.001). A similar pattern of hemodynamic response was observed in both groups. Approximately 1 minute after CaCl2 injection, cardiac index returned to control level, Vpm and mean blood pressure remained elevated, and heart rate declined (p less than 0.01). Systemic vascular resistance gradually increased and was significantly elevated (p less than 0.05) in Group B at 3 minutes and in Group A at 6 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗