The threshold for hypoxia effects on perceptual-motor performance.
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Biomedical subjects
Publications and source records attributed to B Fowler.
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Two experiments were conducted to examine the effects of 35% nitrous oxide (N2O) on rehearsal strategy while learning a list of words in a free-recall paradigm. In experiment 1, the subjects learned the list while rehearsing the words aloud. Learning was slowed and an analysis of the recorded rehearsal protocols revealed a decrease in the overall rate of rehearsal. In addition, there was a decrease in both the number of words rehearsed together and the proportion of words rehearsed from earlier serial positions in the list. In experiment 2, the subjects were required to follow a different rehearsal protocol which was identical for both N2O and the air-breathing control. They had no difficulty following this protocol, but learning was still slowed. These results demonstrate that rehearsal strategies may be modified by narcosis but can be manipulated experimentally. This is consistent with the hypothesis that strategic variables play an important role in the slowed processing model of inert gas narcosis.
This study reports the clinical and pharmacokinetic results following an injection of latamoxef (moxalactam disodium) in patients undergoing cholecystectomy for symptomatic cholelithiasis. Two groups were involved in the study. Group A consisted of 22 patients who received 1 g of intramuscular latamoxef at the time of premedication prior to surgery, and group B consisted of 12 patients each of whom received an intravenous dose of 0.5 g of latamoxef at the time of anaesthetic induction. Latamoxef levels were then measured in peripheral blood, gall bladder bile, common bile duct (CBD) bile and gall bladder wall. Despite a significant difference in the sampling times, inhibitory levels were obtained in the majority of samples in both groups, singularly high levels being assayed in CBD bile. We conclude that an intravenous dosage of latamoxef (0.5 g) given with anaesthetic induction is as effective as 1 g intramuscular dosage given with the pre-medication.
The effects of ethyl alcohol (1 ml/kg body weight), dextroamphetamine (15 mg), and nitrous oxide (20%) on reaction time were investigated in 6 subjects with a 2-, 3-, and 4-choice serial reaction time task. Each drug was assessed separately and in combination with nitrous oxide. The error rate was held constant. Neither ethanol and nitrous oxide nor amphetamine and nitrous oxide influenced the slope of the Hick-Hyman function, but the former combination increased the intercept while the latter decreased it. The drugs, either alone or in combination, shifted the frequency distributions of the reaction times as a whole, rather than modifying either their shapes or the pattern of the response latencies around an error. These results indicate that the drugs have a common pattern of effects on reaction time and that alcohol exacerbates narcosis while amphetamine ameliorates it. This is interpreted as support for the view that narcosis causes a nonspecific slowing of information processing by decreasing arousal.
A study was conducted to examine the vestibular ocular reflex (VOR) during narcosis. The slow phase velocity of the nystagmus was measured in six subjects by means of electronystagmography during the inhalation of 25% nitrous oxide. It was found that nitrous oxide increased the velocity of the slow phase component of the VOR by approximately 50%. This result indicates that the gain of the VOR is effectively increased during nitrous oxide induced narcosis. It appears that the vestibular end organs and/or the central pathways controlling nystagmus are affected by nitrous oxide and this may be a reason for the disruption in balance associated with inert gas narcosis.
Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency. It is unknown whether heterozygosity for homocystinuria predisposes to premature vascular disease. We explored the frequency of excessive homocysteine accumulation after standardized methionine loading in 75 patients presenting with clinical signs of ischemic disease before the age of 50:25 with occlusive peripheral arterial disease, 25 with occlusive cerebrovascular disease, and 25 with myocardial infarction. In seven patients in each of the first two groups but in none of the patients in the third group, heterozygosity for homocystinuria was established on the basis of pathological homocysteinemia after methionine loading and cystathionine synthase deficiency in skin fibroblast cultures. Because the frequency of heterozygosity for homocystinuria in the normal population is 1 in 70 at the most, we conclude that this condition predisposes to the development of premature occlusive arterial disease, causing intermittent claudication, renovascular hypertension, and ischemic cerebrovascular disease.
Previous data on tentative identification of the carrier state for homocystinuria due to cystathionine synthase deficiency using methionine loading or measurement of cystathionine synthase activity in tissue extracts are conflicting. We studied the results of standardized oral methionine loading in 20 obligate heterozygotes and compared them with those of determination of cystathionine synthase activity in cultured fibroblasts. Special attention was devoted to our recently reported observation on the small but striking differences in methionine metabolism between healthy pre- and postmenopausal women and men. Fasting and after load peak levels of methionine in serum did not discriminate the carriers from the control subjects. The mean fasting level of total homocysteine was only significantly higher in the group of premenopausal heterozygotes than in the corresponding control group. Nevertheless, the individual values overlapped with the normal range in 4 of 12 premenopausal heterozygotes. After loading peak levels of total homocysteine in 18 out of the 20 obligate heterozygotes exceeded the upper limit of the ranges in the three control groups. Thus, this parameter discriminated 90% of the obligate carriers. Measurement of cystathionine synthase activity in cultured fibroblasts from a skin biopsy identified the obligate heterozygotes to a similar degree (85%). No significant correlation between the measurements of cystathionine synthase activity and the after load peak levels of total homocysteine in the individual heterozygotes was established. Combination of both methionine loading and determination of cystathionine synthase activity in cultured fibroblasts identified all of these carriers.
Pyridoxine metabolism is summarised and speculation on possible defects leading to disease is made. Inherited deficiencies of PLP enzymes, which are known to respond in vivo to pharmacologic doses of pyridoxine are listed. The mechanism of pyridoxine responsiveness in homocystinuria due to cystathionine beta-synthase deficiency is discussed. There is a correlation in most (but not all) cases between the presence of residual CS activity, which is often stimulated by pyridoxal phosphate much more than control enzyme, in cultured fibroblasts and pyridoxine responsiveness in vivo. Exceptional patients have been found and are discussed in the light of more detailed studies on their cell lines. Clearly defined abnormalities of pyridoxal phosphate binding to mutant enzyme have been demonstrated and evidence of reduced intracellular stability of mutant CS and possible modulation by pyridoxal phosphate is presented. Preliminary findings suggest that the tissue level of pyridoxal phosphate achieved following pyridoxine treatment could be one other factor in determining pyridoxine responsiveness.
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The effects of inert gas narcosis on behavior before unconsciousness are reviewed with particular attention to four issues. The first is whether the qualitative behavioral effects of all inert gases are identical. Evidence is limited but does not contradict an affirmative answer. This is consistent with the unitary hypothesis of narcosis at the physicochemical level. The second issue concerns the relative merits of four approaches to narcosis; (a) the descriptive model, (b) the hierarchical organization hypothesis, (c) the operant paradigm, and (d) the slowed processing model. It is concluded that the latter two are showing some promise. In particular, operant techniques allow more sophisticated measures of narcosis in animals than behavioral end points, such as loss of the righting reflex. The slowed processing model claims that the majority of performance deficits in humans are caused by a single fundamental deficit, slowing of information processing due to decreased arousal. This slowing is usually accompanied by alterations in task strategy. These alterations, in combination with cumulative slowing in working memory, are said to account for the various manifestations of narcosis on complex tasks. The third issue concerns adaptation to narcosis. There is some evidence that adaptation can occur but it is unclear whether the cause is learning specific to narcosis or development of a physiological tolerance. However, adaptation has not always been found and the variables controlling its presence or absence have yet to be identified. The fourth issue concerns the modifying effects of various factors, such as carbon dioxide and anxiety, on narcosis. Methodological and conceptual problems hinder interpretation of the evidence in this area but, contrary to some current views, there appears to be no conclusive evidence that any factor other than ethanol potentiates narcosis. Some implications of these conclusions for diving operations are discussed.
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After pre-operative administration of 1 g, latamoxef disodium (moxalactam) levels were measured in peripheral venous blood, skeletal muscle and subcutaneous fat sampled from 29 patients during either arterial reconstruction or amputation undertaken for arterial occlusive disease. Tissue samples were taken from both proximal and distal levels in the amputated limbs. Levels of latamoxef disodium were above the minimum inhibitory concentration required for most commonly encountered Gram-positive and Gram-negative organisms. No patients developed toxicity or superficial wound infection but there was one vascular graft infection by Candida albicans. It has been shown that latamoxef disodium penetrates rapidly into the subcutaneous fat and skeletal muscle of relatively ischaemic limbs, achieving levels inhibitory to many common pathogens.
Studies were undertaken to determine the effect of host zinc deficiency upon the distribution of Cd, Zn and Cu between and within male rat kidney cytosol and unfractionated cell pellet. In the first experiment male rates were fed stock diets supplemented with 100 micrograms Cd/mL in the drinking water for 30 days. Then Cd-treated rats and controls were segregated into groups, which received semipurified diets adequate or deficient in zinc for 14 days. After this regimen there were comparable concentrations of total Cd and metallothionein bound Cd in cytosol and the supernatant of sonicated, unfractionated pellet on a microgram Cd/g protein basis. Although less than 5% of cytosolic Cd is not bound to metallothionein (MT), 3-5 times as much non-MT Cd is present in the particulate fraction. The zinc-deficient (Zn-) dietary regime increases the non-MT Cd in the pellet. Quantitations were done of the Cu and Zn distribution in high molecular weight, superoxide dismutase, and metallothionein regions of the profiles of metals from Sephadex G-75 chromatography. In animals exposed to Cd and fed a zinc-normal (Zn+) diet, supernatant and pellet metal contents only change in the MT fraction. Similarly, zinc deficiency affects primarily the complement of metals bound to metallothionein: zinc is markedly decreased and Cu is lowered to a smaller extent. Cadmium is unchanged. Control kidney, unexposed to Cd, normally contains a substantial amount of Zn,CuMT. Two-week zinc deficiency greatly reduces MT-Zn and -Cu content without altering the metal content of other cellular pools.(ABSTRACT TRUNCATED AT 250 WORDS)
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The ability of human skin-fibroblasts in monolayer culture to carry out transsulphuration and remethylation of homocysteine has been tested. The conversion of homocyst(e)ine ot cyst(e)ine and methionine was studied in control and mutant cells by incubation for 16 h with L-[35S] homocystine. Labelled cysteic acid and methionine sulphone were found in hydrolysates of oxidized cell proteins. The quantities found were dependent on the time of incubation and were used as a measure of cyst(e)ine and methionine formation, respectively. In control cells, labelled cyst(e)ine and labelled methionine were found. In cystathionine beta-synthase-deficient cell lines, labelled cyst(e)ine formation was reduced, while labelled methionine formed was similar to that of controls, indicating the role of transsulphuration in the formation of cyst(e)ine observed in control cells. In a 5,10-methylenetetrahydrofolate reductase-deficient cell line, labelled methionine formation was reduced, indicating the role of N-5-methyltetrahydrofolate-requiring methylation of homocysteine in the formation of methionine observed in control cells.