Biomedical subjects

J R Foster

Publications and source records attributed to J R Foster.

At least 91 records · Page 5Linked to original sources

PubMed1984

Reproducibility and treatment of exercise-induced ventricular tachycardia.

Fourteen patients with exercise-induced ventricular tachycardia (VT) underwent serial treadmill testing, and those with reproducible arrhythmia were treated with a beta-adrenergic blocking agent. In 11 patients (79%), VT of similar rate, morphologic characteristics and duration was reproduced on 2 consecutive treadmill tests performed 1 to 14 days apart. Beta blockade prevented recurrent VT during acute testing in 10 of 11 patients and during chronic therapy in 9. Eight patients had a consistent relation between a critical sinus rate and the onset of VT. In these patients, successful therapy correlated with preventing achievement of the critical sinus rate during maximal exercise. Thus, serial exercise testing is an appropriate means of assessing efficacy of therapy in patients with exercise-induced VT, provided that reproducibility is established on 2 control tests before beginning treatment. Therapy with beta-blocking agents is effective, especially when guided by the presence of a critical sinus rate-VT relation.

Adult↗

PubMed1984

The Clara cell and pulmonary surfactant: a study using selective chemical ablation.

Administration of 3-hydroxymethylfuran-N-ethylcarbamate (HFC) to female hamsters via the jugular vein under pentobarbitone anaesthetic at 20 mg per kg body weight produced pronounced necrosis of the Clara cells without apparent morphological effect on other cell types as judged by transmission electron microscope examination. The surfactant material recoverable by minimal lavage followed by purification by sucrose gradient ultracentrifugation increased, reaching a maximum around 48 h after treatment. At this time static pressure/volume measurements on isolated lungs indicated an increase in airway surface compliance. Lavageable surfactant phospholipid composition was examined by 31P nuclear magnetic resonance (n.m.r.). The distribution of phospholipids between the various classes was unchanged by HFC treatment. No change in the total lung surfactant pool size was seen. These results are discussed in relation to the possible roles of the Clara cell in influencing airway surfactant levels.

Animals↗

PubMed1984

Bioavailability of digoxin capsules and tablets: effect of coadministered fluid volume.

The effect of different coadministered fluid (water) volumes on the consistency of digoxin absorption was studied in 16 male volunteers. Each volunteer received four single-dose treatments (two 0.25-mg digoxin tablets with 30- and 240-mL of water and two 0.2-mg digoxin capsules with 30- and 240-mL of water). Digoxin present in serum and urine samples collected for 48 h after dosing was quantified by RIA. Treatments were compared by evaluating the following model-independent pharmacokinetic parameters: maximum serum concentration (Cmax); time of maximum serum concentration (tmax); area under the serum concentration-time curve for 0-12 h (AUC0-12); cumulative urinary excretion for 0-48 h (CUE48). No significant differences were found between dosage form (tablets versus capsules) and coadministered water volume (30 mL versus 240 mL) for any of the parameters. For both fluid volumes the AUC0-12 and Cmax were significantly larger (p less than 0.01) and the tmax significantly shorter (p less than 0.01) for the capsules than for the tablets. The volume of coadministered water had no effect on the amount of digoxin absorbed from either dosage form.

Adult↗

PubMed1984

Induced mucosal penetration and transfer to portal blood of luminal horseradish peroxidase after exposure of mucosa of guinea pig small intestine to ethanol and lysolecithin.

The effect of luminal 150 mmol saline, 0.05-0.2% (w/v) lysolecithin, and 5-20% (v/v) ethanol was studied on the mucosal morphology of the proximal small intestine in conscious guinea pigs as well as on the mucosal penetration and transfer to portal venous blood of luminal horseradish peroxidase (HRP). No ultrastructural evidence of mucosal damage was identified in any of the lysolecithin-perfused animals compared with saline controls. Ten and 20% ethanol (v/v) resulted in the appearance of fluid-filled spaces between enterocytes and in cytoplasmic lipid deposits and an increased number of autophagic vesicles within the cells themselves. Tight junctions remained intact. These changes after luminal 5% ethanol (v/v) were much less conspicuous. In the presence of saline, luminal HRP was largely confined to the brush border. Both lysolecithin and ethanol (5% v/v) rapidly induced mucosal penetration of HRP which was seen in cytoplasmic vesicles within enterocytes, between enterocytes, and in the lamina propria. Peak portal venous blood levels of HRP studied in multiple samples over 3 hr were one log unit greater than saline controls. Absorption of HRP was proportional to the luminal concentration of lysolecithin in the range tested. These studies show that mucosal penetration and absorption of functional exogenous macromolecules may be induced, in the absence of morphological evidence of mucosal damage, by luminal constituents which may perturb the structure of enterocyte membranes.

Animals↗

PubMed1984

Myxedema coma during long-term amiodarone therapy.

Amiodarone is a potent new antiarrhythmic drug that has multiple effects on thyroid function, including inhibition of extrathyroidal triiodothyronine production and rarely, iodine-induced hypothyroidism. This report describes a man with recurrent ventricular tachycardia in whom hypothyroidism developed during amiodarone therapy and who died of probable myxedema coma. Parenteral and oral thyroxine therapy promptly reduced serum thyroid-stimulating hormone concentrations without increasing the patient's very low serum triiodothyronine concentration. This response to thyroxine suggests that thyroxine itself may have biologic activity and participate directly in regulation of thyrotropin secretion. Because amiodarone-induced hypothyroidism may be life-threatening, thyroid function should be monitored before and during amiodarone therapy, and the drug discontinued or appropriate therapy instituted if hypothyroidism develops.

Aged↗

PubMed1984

Bacterial infection of the common bile duct in chronic fascioliasis in the rat.

Bile taken from rats infected with the liver fluke, Fasciola hepatica contained spiral bacteria whereas bile from uninfected rats was free from spiral bacteria. The bacterium and its relationship to the bile duct epithelium and the liver fluke was studied with a combination of light microscopy, scanning and transmission electron microscopy. Its morphological characteristics suggest that the bacterium belongs to the genus Spirillum. In contrast to many other co-infections of bacteria and helminths, the present one seems to be a fairly passive relationship so that neither the helminth nor the rat suffers from the presence of bacteria. The presence of the bacteria is thought to be due to changes in the biliary environment, produced as a result of the fluke infection; these changes subsequently allow a multiplication of bacteria normally present in the uninfected animal.

Animals↗

PubMed1984

Comparative studies on di-(2-ethylhexyl) phthalate-induced hepatic peroxisome proliferation in the rat and hamster.

Young male Sprague-Dawley rats and Syrian hamsters were treated with 25-1000 mg/kg/day di-(2-ethylhexyl) phthalate (DEHP) orally for 14 days. Liver enlargement was observed in both species, the magnitude being greater in the rat than in the hamster. In the rat there was a marked dose-dependent induction of the peroxisomal marker cyanide-insensitive palmitoyl-CoA oxidation and also of carnitine acetyltransferase. Little effect was observed on the mitochondrial markers carnitine palmitoyltransferase and succinate dehydrogenase. Whereas in the rat, increased peroxisomal enzyme activities were observed after treatment with 100 and 250 mg/kg/day DEHP, much less effect was observed in the hamster even after 1000 mg/kg/day DEHP. Parallel morphological investigations demonstrated a greater increase in hepatic peroxisome numbers in the rat than in the hamster. 14C-labeled DEHP was found to be more rapidly hydrolyzed by rat than hamster hepatic and small intestinal mucosal cell preparations and differences were also observed in the absorption and excretion of oral doses of [14C]DEHP. Studies with mono-(2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, and a hypolipidemic drug clofibrate also resulted in a greater increase in hepatic peroxisomal enzymes in the rat compared to the hamster. The results demonstrate that while DEHP, MEHP, and clofibrate induced hepatic peroxisome proliferation in both species, there was a marked species difference in response. Comparative long-term studies in these species may thus help to clarify the role of peroxisome proliferation in the hepatocarcinogenicity of DEHP.

Animals↗

PubMed1984

Thymic involution in rats given diets containing dioctyltin dichloride.

Inbred rats fed diets containing 150 ppm dioctyltin dichloride (DOTC) demonstrated a progressive reduction in thymic weight. This was accompanied by a decrease in both the number of circulating lymphocytes and their ability to respond to mitogenic stimulation. Morphologically the thymuses from treated animals showed a loss of cortical thymocytes and a marked vacuolation of the reticular epithelial cells (REC). After return to normal diet for 4 weeks vacuolated REC were still present and PHA-induced lymphocyte blastogenesis remained low. Adrenalectomy failed to alter the atrophic action of DOTC on the thymus and although administration of hydrocortisone alone produced thymic atrophy, no damage to the REC was observed. The results show that thymic atrophy resulting from DOTC administration differs from that induced by steroids and lends support for the hypothesis that DOTC acts selectively on the thymus in such a way that the humoral function of the organ may be affected.

Adrenalectomy↗

PubMed1984

Elective cardioversion in the presence of conduction disturbances.

Elective cardioversion of supraventricular arrhythmias has been demonstrated to be an effective procedure which can be performed with minimal risk. The risks of cardioversion are increased in the presence of digoxin intoxication, failure of synchronization, conversion in the presence of high energies, long standing atrial fibrillation, atrial fibrillation with slow ventricular rates, and dysrhythmias in association with ischemic heart disease or cardiomyopathy. However, the risk of cardioversion of supraventricular arrhythmias in the presence of conduction disturbances, although thought to be increased, has never been carefully studied. This study was designed to examine the effects of conduction disturbances (CD) on the success and risk of elective cardioversion of supraventricular arrhythmias (atrial fibrillation and atrial flutter) and to define the role of temporary pacemakers prior to cardioversion in these patients.

Adolescent↗

PubMed1984

Comparative studies of the hepatic effects of di- and mono-n-octyl phthalates, di-(2-ethylhexyl) phthalate and clofibrate in the rat.

The oral administration of di-n-octyl phthalate (DNOP), mono-n-octyl phthalate (MNOP), di-(2-ethylhexyl) phthalate (DEHP) and clofibrate to young male Sprague-Dawley rats for 14 days resulted in liver enlargement. Morphological examination of liver sections from DEHP and clofibrate treated rats, but not from either DNOP or MNOP treated animals, revealed increased numbers of peroxisomes (microbodies). Both DEHP and clofibrate treatment markedly stimulated the activities of certain peroxisomal marker enzymes whereas DNOP and MNOP produced only marginal effects. Similarly both DEHP and clofibrate, but not DNOP or MNOP, increased microsomal cytochrome P-450 content and markedly stimulated microsomal lauric acid hydroxylation activity. The results thus demonstrate that whilst the branched chain phthalate ester DEHP induced peroxisomal proliferation, the straight chain analogue DNOP and its metabolite MNOP were essentially inactive. In addition, DEHP treatment appeared to induce similar form(s) of cytochrome P-450 in rat liver to those previously described after clofibrate administration.

Animals↗

PubMed1984

Testicular toxicity produced by ethylene glycol monomethyl and monoethyl ethers in the rat.

Ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE) were administered orally to young male rats at doses varying from 50 to 500 mg/kg/day and 250 to 1000 mg/kg/day for EGME and EGEE, respectively, for 11 days. At sequential times animals were killed and testicular histology examined. The initial and major site of damage following EGME treatment was restricted to the primary spermatocytes undergoing postzygotene meiotic maturation and division. EGEE produced damage of an identical nature, but a larger dose was required to elicit equivalent severity (500 mg EGEE/kg being approximately equivalent to 100 mg EGME/kg). Additionally, within the spermatocyte population, differential sensitivity was observed depending on the precise stage of meiotic maturation: dividing (stage XIV) and early pachytene (stages I-II) greater than late pachytene (stages VIII-XIII) greater than mid-pachytene (stages III-VII). Equivalent doses of methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) gave injury similar to the corresponding glycol ether. When animals were pretreated with inhibitors of alcohol metabolism followed by a testicular toxic dose of EGME (500 mg/kg), an inhibitor of alcohol dehydrogenase (pyrazole) offered complete protection. Pretreatment with the aldehyde dehydrogenase inhibitors disulfiram or pargyline did not ameliorate the testicular toxicity of EGME. In mixed cultures of Sertoli-germ cells, MAA and not EGME produced effects on spermatocytes analogous to that seen in vivo, at concentrations approximately equivalent to steady-state plasma levels after a single oral dose of EGME (500 mg/kg). It would seem likely that a metabolite (MAA or possibly methoxyacetaldehyde) and not EGME is responsible for the production of testicular damage.

Acetates↗

PubMed1983

Vagal syncope during recurrent pulmonary embolism.

The mechanism for syncope during pulmonary embolism is not well understood. We describe two patients with transient sinus bradycardia and atrioventricular (AV) block during syncope from recurrent pulmonary embolism. Consciousness was regained each time the rhythm returned to normal. We believe that the syncope and bradyarrhythmia was caused by a parasympathetic reflex, since simultaneous slowing of the sinus rate with concomitant AV block is a common manifestation of increased vagal tone. Such a reflex is consistent with known cardiac reflexes, may occur frequently, and may be one of the mechanisms for syncope in patients with pulmonary embolism.

Bradycardia↗

PubMed1983

The morphological development of di-N-pentyl phthalate induced testicular atrophy in the rat.

Prepubertal rats treated orally with di-n-pentyl phthalate at 2.2 g/kg body weight were killed at 1, 3, 6 and 24 hr following a single dose, and after 2, 3 and 4 days of repeated daily dosing. At 3 hr Sertoli cells in a proportion of the seminiferous tubules showed vacuolation of the perinuclear smooth endoplasmic reticulum with an associated inward displacement of germinal cells. By 6 hr the vacuolation had extended to the apical cytoplasm and was evident in most tubules. Early degenerative changes were also apparent in spermatocytes and spermatids and were accompanied by an acute interstitial inflammatory infiltrate. By 24 hr, germinal cell degeneration was extensive with desquamation and general disorganisation of cell layers within the epithelium, but the interstitial inflammatory infiltrate had declined. Mitochondrial succinic dehydrogenase activity in Sertoli cells was reduced at 3 and 6 hr and absent by 24 hr. In germinal cells it was unaffected at 3 and 6 hr but absent by 24 hr. Two, three and four days of daily phthalate treatment resulted in a gradual depletion of germinal cells from all tubules, leaving a Sertoli cell matrix containing a few necrotic spermatocytes and occasional normal spermatogonia. The significance of the early Sertoli cell changes is discussed.

Animals↗

PubMed1983

Safety of multiple bolus loading of intravenous disopyramide.

Although a single intravenous bolus of disopyramide is an effective antiarrhythmic, side effects occur in some patients. We tested the safety of multiple bolus loading for intravenous disopyramide in 10 patients with frequent premature ventricular beats. Concurrent with a 1.0 mg/kg/hr infusion, a bolus of 0.5 mg/kg of disopyramide was given over 5 minutes. Up to three additional boluses were given 5 minutes after the first bolus unless a 50% reduction in premature ventricular beats or side effects occurred. The infusion was continued for 3 hours and was then decreased to 0.4 mg/kg/hr for 15 hours. All patients had a 50% reduction in premature ventricular beats and attained therapeutic blood levels. Three patients with a history of controlled congestive heart failure developed either hypotension or pulmonary edema. Hypotension and pulmonary edema following intravenous disopyramide is more related to the pharmacology of the drug than to the loading scheme employed.

Adult↗

PubMed1983

Peroxisome proliferation in primary cultures of rat hepatocytes.

Primary cultures of rat hepatocytes were exposed to a range of chemicals known to cause peroxisome proliferation in vivo. Peroxisomal palmitoyl-CoA oxidation and carnitine acetyltransferase (CAT) activity were increased within 12 to 24 hr of adding 0.5 mM clofibrate to the culture medium, reaching about 20 times control levels after 72 hr. Stimulation of CAT activity was dose related over a concentration range of 0.05 to 2 mM clofibrate and 0.02 to 0.2 mM mono-2-ethylhexylphthalate (MEHP). Higher concentrations of MEHP were cytotoxic. The stimulation of CAT activity and palmitoyl-CoA oxidation produced by clofibrate and MEHP was inhibited by cycloheximide. In further studies with clofibrate and a range of other known peroxisome proliferators (nafenopin, tiadenol, BR-931, Wy-14,643, and acetylsalicylic acid), induction of CAT and palmitoyl-CoA oxidation was observed with no increase in activity of another peroxisomal enzyme, D-amino acid oxidase. This differential effect on peroxisomal enzyme activity is typical of that seen in vivo. Furthermore, the relative potencies of the different peroxisome proliferators in vitro agreed well with what is known from studies in vivo. Mitochondrial and microsomal marker enzymes showed little change in activity. Electron microscopy of treated cultures revealed increased numbers of peroxisomes, some of which lacked the characteristic nucleoid. The results indicate that primary cultures of rat hepatocytes provide a rapid, sensitive means of identifying chemicals that cause peroxisome proliferation and a potentially valuable system for studies aimed at clarifying the toxicological significance of this phenomenon.

Animals↗

PubMed1983

Testicular toxicity of ethylene glycol monomethyl and monoethyl ethers in the rat.

Ethylene glycol monomethyl (EGM) and monoethyl (EGE) ethers were administered po to rats at dosages varying from 50 to 500 mg/kg body weight/day for EGM and 250 to 1000 mg/kg body weight/day EGE for 11 days. First evidence of testicular damage following EGM treatment was observed 24 hr after a single dose of 100 mg/kg body weight when the lesion appeared localized in the primary spermatocyte. At 16 hr after a single dose of 500 mg/kg, mitochondrial damage was one of the first subcellular changes to be demonstrated. Treatment of animals with EGE resulted in a similar lesion; however, to obtain damage of equivalent severity, a larger dosage for a longer period was required. In limited studies with 2-methoxy- and 2-ethoxyacetic acids (putative metabolites of EGM and EGE, respectively), using equimolar doses to their parent compounds (500 mg EGM or EGE/kg for 4 or 11 days, respectively) gave damage of equivalent severity to the corresponding glycol ether. After dosing animals with 500 mg EGM/kg body weight for 4 days, the testes recovered weight, and the majority of tubules recovered their spermatogenic potential within one full maturation cycle. The recovery study also indicated a possible effect on the spermatogonia in a small number of tubules although no morphological abnormalities to this cell type could be observed. No effect levels over the 11-day treatment period were 50 and 250 mg/kg body weight/day for EGM and EGE, respectively.

Animals↗

PubMed1983

Peroxisomal effects of phthalate esters in primary cultures of rat hepatocytes.

Primary rat hepatocyte cultures were used to compare the effects of some alkylphthalate esters on peroxisomal enzyme activities and morphology. Linear diesters from methyl to n-octyl and their constituent monoesters and alcohols were compared with the branched chain 2-ethylhexyl derivatives. Carnitine acetyltransferase activity was increased 9.5-fold by mono-2-ethylhexylphthalate (MEHP) and 5.5- and 7-fold by mono-n-pentyl- and mono-n-octylphthalate (MNOP), the 2 most potent of the linear monoesters. Activity of the specific peroxisomal marker, cyanide-insensitive palmitoyl-CoA oxidation decreased with time in control cultures. Whereas MEHP produced a time related increase over the initial level of palmitoyl-CoA oxidation, MNOP treatment only maintained the initial level of activity. The peroxisome proliferation-associated 80 000 mol. wt polypeptide was induced by MEHP but not MNOP. Similarly, MEHP produced increased numbers of peroxisomes, many without a nucleoid, whereas MNOP and mono-n-pentylphthalate had no such effect. 2-Ethylhexanol was less potent as an inducer of carnitine acetyltransferase than MEHP and the linear alcohols had no effect on this enzyme. Studies with diesters indicated that induction of carnitine acetyltransferase required hydrolysis of the diester. It is concluded that the straight-chain phthalates studied have little effect on hepatic peroxisomes compared with the 2-ethylhexyl ester and that hepatocyte cultures provide a rapid means of comparing the peroxisomal effects of different phthalates.

Animals↗

PubMed1983

Exercise-induced distal atrioventricular block.

Three patients with 1:1 atrioventricular (AV) conduction at rest developed fixed 2:1 or 3:1 AV block during treadmill exercise testing. Electrophysiologic study documented block distal to the AV node in all three patients, and suggested that the exercise-induced block occurred because of increased atrial rate and abnormal refractoriness of the His-Purkinje conduction system. The findings in these three patients suggest that high grade AV block appearing during exercise reflects conduction disease of the His-Purkinje system rather than of the AV node, even in the absence of bundle branch block. Patients with this diagnosis should be considered for permanent cardiac pacing.

Aged↗