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Biomedical subjects

E Gordon

Publications and source records attributed to E Gordon.

At least 181 records · Page 10Linked to original sources

Increased alcohol dehydrogenase independent ethanol oxidation at high ethanol concentrations in isolated rat hepatocytes: the effect of chronic ethanol feeding.

Rates of ethanol oxidation in isolated rat hepatocytes increased with increasing ethanol concentrations even at near-saturation of the alcohol dehydrogenase (ADH) pathway. After inhibition of ADH by pyrazole, approximately 30% of ethanol-oxidizing activity remained and this activity of the non-ADH pathway was also dependent upon ethanol concentration. The apparent Km of th non-ADH pathway for ethanol was 13 mM, which is comparable to the value for the microsomal ethanol oxidizing system. Inhibition of catalase by azide affected the activity of the non-ADH pathway by less than 10%. After chronic ethanol feeding, the rates of ethanol oxidation in isolated hepatocytes and liver slices increased significantly compared to those in pair-fed controls. This adaptive increase of ethanol oxidation was more striking at a high ethanol level (30 mM) than at a low one (10 mM). Significant differences between the two groups remained even after inhibition of ADH and catalase. The results suggest that the microsomal ethanol oxidizing system may account for the major part of the non-ADH pathway.

Alcohol Oxidoreductases↗

Familial hypercholesterolaemia--a common genetic disorder in the Afrikaans population.

Serum cholesterol levels have been studied in three groups of young White South Africans. The mean levels were highest among the Jewish (195,7 mg/dl or 5,10 mmol/l), lowest among the Afrikaans (174,9 mg/dl of 4,55 mmol/l), and intermediate in the English-speaking Gentile population (180,0 mg/dl or 4,67 mmol/l). Levels were significantly higher in females than in males in the Jewish and English-speaking Gentile populations, but not significantly higher in Afrikaans females compared with males. Studies carried out on the families of individuals found to have serum cholesterol levels above 300 mg/dl (7,8 mmol/l) emphasized that, in addition to the serum cholesterol studies, detailed family studies are essential if an accurate diagnosis of familial hypercholesterolaemia (FH) is to be made. From such studies in the Afrikaans population and also from the known number of homozygotes for FH in one area of South Africa, all of whom came from Afrikaans families, it has been estimated that the frequency of the FH gene is unusually high in this population. It is postulated that the latter finding could help to explain the high incidence of and mortality rate from ischaemic heart disease in young White South Africans.

Adolescent↗

The effect of chronic ethanol consumption on pathways of ethanol metabolism.

The contribution of the known hepatic pathways for the disposal of ethanol was studied utilizing two different experimental designs. In vitro studies were carried out in hepatocytes isolated from rats fed Purina chow. Rates of ethanol oxidation in these preparations increased with increasing levels of ethanol (10-50 mM). After inhibition of alcohol dehydrogenase (ADH) by pyrazole (2 mM) and the catalase by azide (1 mM) approximately 25% of the ethanol oxidizing activity remained. The residual activity was also dependent upon ethanol concentration and the apparent Km was 13 mM. Hepatocytes from ethanol-fed rats exhibited rates of ethanol oxidation which were also dependent upon the concentration of ethanol. The rates were higher in the hepatocytes from the ethanol-fed rats than in the controls. The addition of inhibitors of ADH and catalase lowered the rates, but abolished neither the differences nor the concentration dependency. In the in vivo studies, ethanol elimination rates were measured in alcohol-fed and control baboons by using a constant ethanol infusion to maintain blood ethanol at three different levels: 5, 10 or 50 mM. Ethanol elimination rate was accelerated with increasing concentration, particularly in alcohol-fed baboons. These observations indicate that a pathway other than the low Km alcohol dehydrogenase participates in alcohol oxidation and is responsible in part for the adaptive increase in ethanol metabolism associated with chronic ethanol consumption.

Alcoholism↗

Cardiovascular effects of sodium nitroprusside in cerebral aneurysm surgery.

Cardiovascular effects of sodium nitroprusside (SNP) were studied in 17 patients undergoing cerebral aneurysm surgery under controlled hypotension. In 10 patients oxygen uptake was also calculated. Mean arterial blood pressure was decreased from 91 to 58 mmHg by SNP due to reductions in both total peripheral resistance (29%) and cardiac output (15%). Mean right atrial and pulmonary capillary wedge pressures were reduced during hypotension. Total oxygen uptake remained constant throughout the procedure. There was no significant change in arterial oxygen tension in the hypotensive period, but after discontinuation of SNP infusion it was significantly increased. The haemodynamic effects of SNP in patients with a recent subarachnoid haemorrhage and its effect on blood oxygenation are discussed. It is concluded that the fall in cardiac output is related to a reduction of central blood volume and might be more pronounced in these patients than in normal subjects.

Adult↗

Sodium nitroprusside as a hypotensive agent in intracranial aneurysm surgery.

Sodium nitroprusside (SNP) was used to induce hypotension during intracranial aneurysm surgery in 67 patients. The effects of SNP infusion (0.1 mg/ml) on blood pressure were rapid and it was easy to adjust blood pressure to desired levels in most patients. When SNP was stopped, the blood pressure returned instantly to the initial level. In eight patients an increase to about 25% or more above prehypotensive level was seen, counteracted in two patients by administration of small doses of halothane. There was a mean increase of 36% in heart rate. Total doses of SNP were 0.05--120 mg (mean: 10.8), corresponding to 0.08--6.8 micrograms/kg/min (mean: 1.9). No metabolic acidosis indicating cyanide intoxication was observed. Tachyphylaxis was seen in three patients, and SNP had to be discontinued in one. It is concluded that SNP gives a rapid and effective hypotension but tachyphylaxis and subsequent danger of cyanide intoxication exist. Therefore, in some cases SNP has to be replaced by or combined with some other hypotensive agent to achieve the desired effect. As there is a risk of impairment of cerebral autoregulation after the use of SNP, it is important to avoid sudden and prolonged blood pressure fluctuations, and to continue with controlled hyperventilation in the postoperative period to reduce the risk of brain oedema and high intracranial pressure.

Adolescent↗

Patient attitudes about two forms of printed oral contraceptive information.

The desired form and style of written drug information for patients were assessed in a national survey of oral contraceptive (OC) users. These women were queried about two forms of OC information: a short insert included with dispensed drugs and a longer brochure delivered by the physician upon patient request. Longer and more detailed information, especially concerning drug dangers and directions for use, was strongly preferred. Younger and more educated women were more likely to report receiving the OC brochure and to desire more comprehensive information. Most respondents found information in both the insert and the brochure clear and useful, and felt it was important to include written information with other prescription drugs. The longer brochure was preferred over the shorter insert as a model of drug information to be included with additional drugs.

Adolescent↗

A survey of the effects of oral contraceptive patient information.

A nationwide survey of 1,720 current and 949 former oral contraceptive (OC) users gathered information about receipt, readership, knowledge, opinions, and reported behavioral changes induced by two forms of patient-oriented OC information. A substantial majority of women said they received and read the patient insert dispensed with the drug. However, only about one third of pill users said that they received the longer informational brochure supplied by physicians on patient request. Directions for use and side effects were the most often recalled information. Physician-patient contact patterns were reported as generally unaffected by written patient information. Respondents preferred the longer informational brochure to the insert. Survey results have implications for recently proposed changes in required OC patient information and for the development of patient information on additional prescription drugs.

Adolescent↗

Platelet and plasma amine oxidase inhibition and urinary amine excretion changes during phenelzine treatment.

The treatment of depressed patients with the monoamine oxidase (MAO)-inhibiting antidepressant, phenelzine, was found to be accompanied by an 82 per cent reduction in platelet MAO activity and a 91 per cent reduction in plasma amine oxidase activity. Maximum reductions in enzyme activity occurred after 7 to 14 days of treatment; recovery of enzyme activity posttreatment required an average of 14 days for the platelet MAO and greater than 6 weeks for the plasma enzyme. Marked elevations in urinary tryptamine excretion occurred in conjunction with MAO inhibition during phenelzine treatment, but the magnitidue of urinary tryptamine change in individual patients was not closely correlated with the magnitude of enzyme activity reduction. Changes in platelet serotonin content serotonin content and in urinary catecholamine metabolites also occurred in response to phenelzine treatment.

Blood Platelets↗

Myocardial lipids and nucleotides of rats fed olive oil or rapeseed oil.

After 1 week, the level of myocardial fatty acids was 4 times greater in young rats fed high erucic rapeseed oil than in those fed oliver oil. The proportion of erucic acid was 5.6% in the mitochondrial fraction, 15.1% in the microsomal fraction, and 34.8% in the floating fat fraction. This incorporation of erucic acid into triglycerides of the floating fat was evidence of esterification. The changes in the mitochondrial lipids did not alter the content of adenine nucleotides of the myocardium nor its apparent capacity to oxidize substrates.

Adenine Nucleotides↗

The antagonist effect of naloxone hydrochloride after neuroleptanaesthesia during neurosurgery.

The effects of naloxone were studied in 82 patients undergoing intracranial surgery under general anaesthesia with fentanyl or phenoperidine. After the operation was finished the patients' alertness, sensitivity to pain, blood pressure, pulse rate, respiratory rate, tidal and minute volume were recorded parallel with arterial blood gas analyses prior to and immediately after the administration of varying amounts of naloxone i.v. in a single dose. These parameters were also repeatedly controlled for several hours in the postoperative period. The results show that a single i.v. naloxone dose of 1 mug/kg b.w. is effective in the rapid and definite reversal of the respiratory depression caused by the analgesics. This dose was neither correlated to the total amount of analgesics given, nor to the time period which elapsed between the last dose of the analgesic drug and the administration of naloxone. No side effects or complications were encountered when the indicated doses of naloxone were given. It is concluded that, even in a small single dose, naloxone effectively antagonises the respiratory depression caused by fentanyl and phenoperidine without totally eliminating the immediate postoperative analgesic effects of these agents.

Adolescent↗

Post-traumatic and postoperative treatment of severe brain injuries with controlled hyperventilation.

Controlled hyperventilation has shown to be an effective method of treatment in patients with pronounced brain edema and high ICP caused by accidental or surgical damage. This treatment has to be started as early as possible after the injury to avoid secondary changes and spreading cerebral edema leading to the impact of the brain-stem and thus irreversible brain damage. If conducted consequently, controlled hyperventilation will diminish mortality rate and increase the rate of valuable recoveries in all sorts of brain injuries.

Brain Edema↗

Studies on immunity with three species of avian trypanosomes.

The ability of three species of avian trypanosome, Trypanosoma corvi, T. bouffardi and T. everetti, to protect against heterologous and homologous challenge has been studied in susceptible birds. None protects against challenge with either or both of the other two species and mixed infections can be obtained experimentally. With T. bouffardi, both apparently sterile and premune states exist after initial infection and the host is immune to challenge with homologous strains; heterologous strains sometimes break this immunity and produce shorter, lower parasitaemias. T. everetti remains in the circulating blood for long periods at low levels and challenge doses with the homologous strain result in a slightly elevated parasitaemia for a few days. T. corvi produces a degree of immunity after the initial infection which usually results in a reduced second parasitaemic peak of shorter duration when birds are challenged with a homologous strain.

Animals↗

Photoaffinity labeling of the ribosomal A site with S-(p-azidophenacyl)valyl-tRNA.

S-(p-Azidophenacyl)valyl-tRNA, an analog of valyl-tRNA which has a photoaffinity label attached to its 4-thiouridine residue, was bound to the ribosomal A site at 10 mM Mg2+. Binding was stimulated 25-fold by the presence of elongation factor EFTu. Photoactivation of the p-azidophenacyl group by irradiation resulted in covalent linking of 6% of the noncovalently bound tRNA to the ribosomes. Covalent linking was dependent on the simultaneous presence of ribosomes, poly(U2,G),EFTu.GTP, required irradiation, and did not occur when S-(phenacyl)valyl-tRNA, a nonphotolyzable analog, replaced S-(p-azidophenacyl)valyl-tRNA. The attached tRNA was distributed approximately equally between both the 30S and 50S subunits. At the 30S subunit, 30% of the tRNA was bound to protein while 70% was linked to 16S RNA. At the 50S subunit, however, negligible binding to the 23S RNA was observed. More than 90% of the tRNA was attached to low molecular weight material according to sodium dodecyl sulfate-sucrose gradient analysis, and more than 87% of this fraction consisted of tRNA-protein complexes as assayed by phenol solubility and electrophoretic mobility before and after protease treatment. These results, in conjunction with our previous report (I. Schwartz and J Ofengand (1974), Proc. Natl. Acad. Sci. U.S.A. 71, 3951) which showed that covalent linking of this same tRNA derivative at the ribosomal P site resulted in attachment solely to the 16S RNA, demonstrate that 16S, but not 23S or 5S rRNA, is an important component of the tRNA binding site in the region of the 4-thiouridine residue and furthermore show that ribosomal A and P sites are topologically distinct.

Affinity Labels↗