Search PubMed⌕ Search

Biomedical subjects

R D White

Publications and source records attributed to R D White.

At least 199 records · Page 11Linked to original sources

Misonidazole as a chemosensitizer in the treatment of the Dunning prostate cancer model.

Utilizing a Dunning prostate tumor model, we investigated the ability of misonidazole, a compound with known radiosensitizing properties, to act as a chemosensitizer when administered in combination with the alkylating agent cyclophosphamide. This combination caused a decrease in tumor growth rate when compared to the growth of the tumor in animals receiving cyclophosphamide alone. However, only at toxic levels was this decrease statistically significant (p less than 0.01).

Animals↗

High-energy versus low-energy defibrillation: experience in patients (excluding those in the intensive care unit) at Mayo Clinic-affiliated hospitals.

/he purpose of this study was to determine whether electric shocks of low (200 to 240 J), intermediate (300 to 320 J), or high (400 to 440 J) delivered energy were most successful in defibrillating hospitalized patients (excluding those in intensive care units) in whom resuscitation was attempted by a code emergency team. From January 1980 through December 1982, 101 cases of ventricular fibrillation in 100 patients were treated by Mayo Clinic code emergency teams. Many of the patients in this trial had secondary or agonal ventricular Defibrillation. Most patients (64%) were defibrillated by one to eight shocks. For the first shock, intermediate and high energy seemed to be more effective than low energy. Patient weight, time of delivery of shock 1 after onset of the code emergency, blood pH, acute and chronic medical diagnoses, and pharmacotherapy before the onset of ventricular fibrillation were not clearly related to the response to shock 1. Nine of 16 patients who did not initially respond to shocks of low or intermediate energy were defibrillated when higher energy was subsequently used. Only 14 patients ultimately survived and were dismissed from the hospital. These results suggest that in this patient population, high levels of delivered energy are preferable to low energy for the first shocks administered; we recommend that 400 J of delivered energy be used initially. The 360-J maximal energy dose available in most currently manufactured defibrillators should be sufficiently close to this recommendation to justify use of that dose with the initial shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Controversies in out-of-hospital emergency airway control: esophageal obstruction or endotracheal intubation?

Maintaining an unobstructed airway and providing adequate oxygenation and CO2 elimination, by artificial means if necessary, are among the highest priorities in all life-threatening circumstances. How this goal can best be met in the prehospital setting has become a controversial issue. The esophageal obturator airway (EOA) frequently is used in the prehospital setting, but its use and effectiveness recently have been criticized. A critical review of available literature reveals two areas of concern: 1) many clinical studies do not address prehospital airway management, and 2) the EOA has only one advantage over mask techniques for artificial ventilation, ie, it reduces the likelihood of aspiration of gastric contents. This advantage was the only one postulated by initial investigators. Many perceived EOA problems are due to poor mask fit and can be rectified. Although endotracheal intubation is the accepted standard for airway management in the apneic patient, its limitations in the prehospital setting are many. These utilization problems and complications remain undefined and must be addressed.

Emergencies↗

Antifibrillatory drugs: the case for lidocaine and procainamide.

Ventricular fibrillation (VF), in most instances, is sustained by multiple wavefronts. The most important prerequisites for development and maintenance of VF are inhomogeneity in activation and recovery and shortening of refractoriness. If drugs are to be effective in removing VF or facilitating its electrical removal, this should occur by alteration of these electrophysiologic mechanisms. Assessment of the antifibrillatory properties of many drugs has been compromised by at least two factors: 1) the questionable appropriateness of the model, and 2) the failure to distinguish between prevention of VF and removal, or facilitation of electrical removal, of VF. Most instances of VF encountered clinically are secondary to acute ischemia; therefore, the most applicable model is acute myocardial ischemia with spontaneous VF. In this setting little is known about the effectiveness of lidocaine (L) or procainamide (PA). While there is more information regarding the role of L in prevention of VF, and of both L and PA in elevating ventricular fibrillation threshold, there is a lack of data on the roles of either drug in removal of existing VF. Thus we are left to speculate on the actions of L and PA that may account for their usefulness in the treatment of VF. These actions are the basis for a projection of the role of L and PA in the treatment of VF. There is evidence in animal models of acute myocardial ischemia to support the use of at least lidocaine in VF.

Electrophysiology↗

Substituted benzaldehydes designed to increase the oxygen affinity of human haemoglobin and inhibit the sickling of sickle erythrocytes.

Substituted benzaldehydes have been designed to bind preferentially to the oxy conformation of human haemoglobin at a site between the amino terminal residues of the alpha-subunits. Such compounds should stabilize the oxygenated form of haemoglobin and thereby increase its oxygen affinity. The compounds produce the expected effect, left-shifting the oxygen saturation curve of dilute haemoglobin solutions and of whole blood, although the binding pattern to haemoglobin is more complex than envisaged by the design hypothesis. The predicted best compound is also a potent inhibitor, at low oxygen pressure, of the sickling of erythrocytes from patients homozygous for sickle cell disease, and may prove to be a clinically useful anti-sickling agent.

2,3-Diphosphoglycerate↗

Mutagenic responses of tansy ragwort (Senecio jacobaea) plant, pyrrolizidine alkaloids and metabolites in goat milk with the Salmonella/mammalian-microsome mutagenicity test.

Tansy ragwort (Senecio jacobaea ) was evaluated for animal and human health hazard using the Salmonella/mammalian-microsome mutagenicity test. An acetone extract of tansy ragwort (TR) produced a negative mutagenic response for bacterial tester strains TA1535 and TA100 and a toxic response in tester strains TA1537 and TA98. Assay of this extract in the presence of mammalian liver microsomes (S-9) resulted in positive mutagenic responses in tester strains TA1535, TA1537, TA98 and TA100. Species differences were evaluated by use of liver microsome preparations from induced rat and uninduced sheep, beef, hamster, trout and rat. Only a slight species difference was demonstrated. A mixture of pyrrolizidine alkaloids (PA), extracted from TR flowers, produced a negative response in tester strains TA1535, TA1537, TA98 and TA100. A negative response was also demonstrated when the TR flower PA mixture was assayed with the Salmonella tester strains and induced rat liver microsomes ( IRLM ). A mixture of PA extracted from Senecio longilobus also produced a negative response. The major PA present in TR, jacobine , produced a negative response without and with IRLM exposure in tester strains TA1535, TA1537, TA98 and TA100. Another similar PA, monocrotaline, found in various Crotalaria species also gave a negative response. Milk from TR-fed goats was evaluated for mutagenic response. Milk from goats not receiving TR and from goats receiving TR at a level of 1% of their body weight/day via rumen cannula produced a negative response without liver microsomes present. Milk from TR-fed goats, however, yielded both negative and marginally positive responses for different combinations of tester strains and liver microsome preparations.

Animals↗

Effects of dietary copper and molybdenum on tansy ragwort (Senecio jacobaea) toxicity in sheep.

Dried tansy ragwort (Senecio jacobaea), which contains pyrrolizidine alkaloids (PA), was fed to sheep to determine whether PA consumption influenced liver Cu concentrations. Nine Polypay wether lambs were allotted to 3 groups according to the diets: control diet + 50 micrograms of Cu/g of feed (control + Cu); tansy ragwort (TR) diet + 50 micrograms of Cu/g of feed (TR + Cu); and TR diet + 50 micrograms of Cu/g of feed and 10 micrograms of Mo/g of feed (TR + Cu + Mo). Liver Cu concentrations were sharply increased (13-fold) after 8 weeks of feeding the diets, and then decreased slightly. There were no significant differences in concentrations of liver Cu among treatment groups. All lambs in the group fed TR + Cu + Mo died by the end of 23 weeks, with the usual signs of PA poisoning, including liver necrosis, hepatic megalocytosis, and biliary hyperplasia. The TR intake was about 2.7 to 3.0 kg/kg of their initial body weight. All lambs in the group fed the control + Cu diet survived. The results indicated that sheep fed TR do not preferentially accumulate liver Cu. There was an indication that dietary Mo increased susceptibility to TR intoxication.

Animal Feed↗

Deuterium isotope effect on the metabolism and toxicity of 1,2-dibromoethane.

The metabolism, hepatotoxicity, and hepatic DNA damage of 1,2-dibromoethane (EDB) and tetradeutero-1,2-dibromoethane (d4EDB) were compared in male Swiss-Webster mice. In vitro studies that measured bromide ion released from the substrate to monitor the rate of metabolism showed that the hepatic microsomal metabolism of EDB was significantly reduced by deuterium substitution, while metabolism by the hepatic glutathione S-transferases was unaffected. Three hours after ip administration of EDB or d4EDB (50 mg/kg), there was 42% less bromide in the plasmaa of d4EDB-treated mice than in the plasm of EDB-treated mice. This difference demonstrates a significant deuterium isotope effect on the metabolism of EDB in vivo. Although the metabolism of d4EDB was less than that of EDB 3 hr after exposure, the DNA damage caused by both analogs was not significantly different at this time point. At later time points (8, 24, and 72 hr), d4EDB caused significantly greater DNA damage than EDB. Since the decreased metabolism of d4EDB was apparently due to a reduced rate of microsomal oxidation, these data support the hypothesis that conjugation with GSH is responsible for the genotoxic effects of EDB.

Alanine Transaminase↗

The effect of intestinal esterase inhibition on the in vivo absorption and toxicity of Di-n-butyl phthalate.

Inhibition of intestinal mucosal esterases by S,S,S-tributylphosphorotrithioate (DEF) did not alter the gastro-intestinal absorption of di-n-butyl phthalate (DBP) in the rat. After intragastric administration of [14C]DBP to control and esterase-inhibited animals, the disappearance of 14C from the small intestine and the levels of 14C in the blood were not significantly different in the two groups over the first 4 hr. Peak blood levels of 14C occurred 2 hr after dosing in both groups of rats. The circulating [14C]butyl phthalate in the diester form accounted for less than 5% of the total 14C at 2 hr, regardless of intestinal esterase activity. The remaining 14C was associated with mono-n-butyl phthalate or more polar metabolites. These data suggest an important role for pancreatic esterases, which may be protected from DEF-mediated inhibition by storage in zymogen granules, in the metabolism and absorption of DBP.

Animals↗

Delay in the onset of parturition in the rat following prenatal administration of developmental toxicants.

The duration of gestation was determined in Sprague-Dawley albino rats exposed during days 6-18 of pregnancy to diethylstilbestrol (DES) or 3,4,3',4'-tetrachlorobiphenyl (4CB). Each compound produced a delay in the onset of parturition compared to corn-oil-treated controls. The incidence of perinatal mortality was significantly elevated in animals born after 22 days of gestation in both control and treated litters.

Animals↗

An evaluation of acetone extracts from six plants in the Ames mutagenicity test.

Acetone extracts from six plants were evaluated for mutagenic activity with the Salmonella/mammalian-microsome mutagenicity test (Ames) utilizing tester strains TA98 and TA100 and in the presence and absence of induced rat liver microsomes. Extracts from alfalfa (Medicago sativa), lettuce (Lactuca sativa) and thread-leaf groundsel (Senecio longilobus) produced only negative responses. Comfrey (Symphytum officinale) and tansy ragwort (Senecio jacobaea) extracts produced toxic responses that were abolished in the presence of the microsomal bioactivation system. Bracken (Pteridium aquilinum) and tansy ragwort extracts produced positive responses following bioactivation with the liver microsomal system. The results suggest that the Ames mutagenicity test may be of some value in initial evaluations for potential toxic effects of plants consumed by animals and man.

Acetone↗

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

This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.

Aged↗

Thrombocytopenia secondary to trimethoprim-sulfamethoxazole.

Two patients had severe thrombocytopenia while taking trimethoprim-sulfamethoxazole. The mechanism is uncertain, but probably is related to drug interference with folate metabolism. Recovery can usually be expected upon withdrawal of the medication and institution of folic acid therapy.

Acute Disease↗

Waiting to live.

Explore the source record for details and available documents.

Adult↗

Indicators of developmental toxicity following prenatal administration of hormonally active compounds in the rat. I. Gestational length.

Prenatal administration of 3,4,3',4'-tetrachlorobiphenyl, zeranol, or diethylstilbestrol was observed to delay parturition in the rat and result in a concomitant increase in perinatal mortality. Even among control animals, those litters in which birth occurred after the beginning of day 22 of pregnancy contained significantly fewer survivors one day after birth. Increases in the length of gestation were correlated with increased weight of newborn control pups independent of litter size. The relationship between weight and litter size was anomalous, however, in treated animals. Gestational length is a sensitive indicator of a developmental effect even in the absence of overt teratogenicity.

Animals↗

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

The ability of an independently developed QRS point score to estimate the size of infarcts predominantly within the anterior third of the left ventricular was evaluated by quantitative pathologic-electrocardiographic correlation. The study was limited to 21 patients with a single infarct documented by postmortem examination, for whom an appropriately timed standard 12 lead electrocardiogram was available that did not exhibit signs of left or right ventricular hypertrophy, left or right bundle branch block or anterior or posterior fascicular block. At necropsy the heart was cut into five to seven slices. The location and size of the infarct was quantitated by computer-assisted planimetry of the slices. The electrocardiogram of 19 (90 percent) of the patients exhibited either a Q wave or an R wave of no more than 20 ms in lead V2. The infarct in the two patients without this electrocardiographic finding was small, occupying 2 and 3 percent of the left ventricle, respectively. The percent infarction of the left ventricle correlated with the QRS point score (r=0.80). Thus in patients without complicating factors in the electrocardiogram and with a single infarct, the electrocardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarct size.

Adult↗

Errors in measurement and reporting of serum markers in patients with germ cell tumors.

Elevation of the serum value of either human chorionic gonadotropin or alpha-fetoprotein in patients with germ cell testicular tumors is often accepted as evidence for persistent malignancy in the absence of histologic confirmation. These laboratory values are not subject to review and confirmation, unlike histologic diagnosis. We report 3 cases in which serum marker values were incorrectly reported to be elevated by commercial laboratories over a thirteen-month period and suggest a method for handling serum samples to avoid errors in diagnosis.

Adult↗