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Biomedical subjects

B Fowler

Publications and source records attributed to B Fowler.

At least 91 records · Page 5Linked to original sources
PubMed1994

Acute hypoxia fails to influence two aspects of short-term memory: implications for the source of cognitive deficits.

There has been considerable interest in the possibility that short-term memory (STM) plays a role in the cognitive deficits produced by hypoxia. Claims have been made that two aspects of STM are impaired, the storage of information and the speed of retrieval of information, but a close examination of the evidence reveals that the whole issue remains an open question. Each aspect was investigated in a separate experiment using well trained subjects who breathed low oxygen mixtures adjusted to control arterial oxyhemoglobin saturation between 64%-66%. Exp. 1 assessed storage capacity with the dichotic listening paradigm. Hypoxia degraded the accuracy of recall, but this was probably an impairment of auditory perception and there was no evidence that storage was impaired. Exp. 2 assessed retrieval speed with Sternberg's memory scanning paradigm. As expected, hypoxia increased reaction time, but this could be accounted for by the slowing of an early stage of perceptual processing. No evidence was found to indicate that stages involving either retrieval from STM or binary decision were slowed. We conclude that STM storage and retrieval are not directly affected by hypoxia, and propose that either direct or indirect slowing of the central executive of working memory may account for the cognitive deficits produced by this stressor.

Acute Disease↗
PubMed1993

Congenital absence of insulin cells in a neonate with diabetes mellitus and mutase-deficient methylmalonic acidaemia.

We report on a female neonate with diabetes mellitus and methylmalonic acidaemia, who died at age 16 days. Using immunocytochemistry, electron microscopy and in situ hybridisation, we were unable to demonstrate any insulin cells in the pancreatic islets. Methylmalonic acidaemia was caused by a methylmalonyl coenzyme A mutase apoenzyme defect. The metabolic crisis of the methylmalonic acidaemia aggravated the diabetes and may explain the failure of insulin therapy. Our results suggest that the infant suffered from a congenital absence of beta cells associated with a genetically transmitted mutase apoenzyme defect.

Autopsy↗
PubMed1993

Inhibition of human and murine cytosolic epoxide hydrolase by group-selective reagents.

1. Human and murine cytosolic epoxide hydrolase were inhibited by thiol-, imidazole- and carboxyl-selective reagents. They were not inhibited by amino-, guanido- or activated serine-selective reagents. 2. Murine, but not human, cytosolic epoxide hydrolase was inhibited by N-bromosuccinimide, a tryptophan selective reagent. 3. Based on sequence data from peptides isolated from CNBr digests, human and murine CEH share areas of sequence homology. Of the five unique human CEH CNBr peptides sequenced, three shared common sequences with one of the unique murine CEH CNBr peptides. The human and murine CEH peptides with common sequences had between 64 and 78% sequence identity. 4. A cysteine important for the activity of murine CEH appears not to be in the active site as judged by N-phenylmaleimide inhibition in the presence and absence of either (2S,3S)-2,3-epoxy-3-(4-nitrophenyl)glycidol, a competitive inhibitor, or trans-stilbene oxide, a substrate.

Amino Acid Sequence↗
PubMed1993

The slowing of visual processing by hypoxia.

An additive factors method (AFM) experiment was undertaken to determine whether the preprocessing and identification stages of information processing are implicated in the slowing of reaction time (RT) by hypoxia. The subjects (n = 14) responded at two levels of light intensity to pairs of lines that differed in length while breathing a low oxygen mixture that produced arterial oxyhaemoglobin saturations ranging between 64%-66%. The results showed a relatively large interaction between light intensity and hypoxia that was interpreted as evidence for slowing of the preprocessing stage. Differences in line length were plotted in terms of Crossman's confusion function and relatively small interactions with both hypoxia and light intensity were found, reflecting increases in slope. The light intensity x confusion level interaction was interpreted as evidence that AFM assumptions may not have been met completely in this experiment. This leads to the possibility that hypoxia slowed the identification stage indirectly rather than directly, although the latter hypothesis cannot be ruled out entirely at present. It is argued that visual slowing probably plays an important role in the disruption of perceptual-motor tasks by hypoxia.

Humans↗
PubMed1993

Dissociation of the effects of alcohol and amphetamine on inert gas narcosis using reaction time and P300 latency.

Alcohol exacerbates and amphetamine ameliorates the slowing of reaction time (RT) produced by inert gas narcosis. The event-related brain potential P300 was used to determine whether these drug effects involve stimulus- or response-related processes, since P300 largely reflects the time to evaluate a stimulus while RT reflects this time plus the time to select and execute a response. Subjects breathed nitrous oxide (N2O) alone and in combination with ethyl alcohol or dextroamphetamine while responding to visually presented names that differed in probability (the oddball paradigm). N2O slowed P300, but this measure was comparatively insensitive to the exacerbation and amelioration that were indexed by RT. Relative to N2O alone, an RT-P300 difference was found for amphetamine + N2O but not for alcohol + N2O. We conclude that exacerbation involves both stimulus- and response-related processes but amelioration involves only the latter. This pattern of results can be explained by a model in which the drugs modulate slowing via the two energetical dimensions of arousal and activation, which influence stimulus- and response-related processes, respectively.

Action Potentials↗
PubMed1993

Relationship between the event-related brain potential P300 and inert gas narcosis.

It is known that inert gas narcosis slows both reaction time (RT) and the event-related brain potential P300 in a correlated and dose-dependent manner. On the assumption that P300 reflects the time to evaluate a stimulus and RT reflects this time plus the time to select and execute a response, these results have been taken to indicate that the locus of the slowing produced by narcosis is early and influences stimulus evaluation processes. If this is the case, RT and P300 should be slowed identically when cognitive workload is manipulated. To test this prediction, subjects breathed 35% nitrous oxide and responded to differences in the intensity of either visual (Exp. 1, n = 8) or auditory (Exp. 2, n = 10) two-choice oddball stimuli with accuracy controlled at a high level. In both experiments narcosis slowed RT and P300 additively by increasing the intercept rather than the slope of the workload function, but these two measures diverged in one important respect; RT was slowed more than P300, as indicated by an RT-P300 difference analysis. It is concluded that, contrary to previous assumptions, narcosis produces two sources of slowing; one stimulus-related and indexed by P300 and the other response-related and indexed by the RT-P300 difference. Possible mechanisms underlying these sources are discussed.

Adult↗
PubMed1992

Biochemical diagnosis and outcome of 2 years treatment in a patient with combined methylmalonic aciduria and homocystinuria.

We describe a patient with methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism of the Cbl-C type mutant (McKusick 277400). Our case was diagnosed within the first 2 months of life by amino acid analysis (ion-exchange chromatography) and by biochemical studies in cultured fibroblasts ([14C]propionate incorporation, methionine and serine formation). We discuss the clinical course and the biochemical evolution after 2 years of hydroxycobalamin treatment that led to an improvement in general clinical condition and neurological performance.

Amino Acids↗
PubMed1992

On controlling inert gas narcosis.

Ten subjects breathed experimental mixtures of 20% and 35% nitrous oxide (N2O) balanced with oxygen and then aligned a pointer with a target using vision, kinesthesis, or combinations of these senses. In a prior session the subjects had been trained on the task with feedback while breathing N2O. The results showed that N2O did not influence variable error (VE), constant error, (CE), or absolute CE, but perceptual conditions influenced VE and absolute CE. These results suggest that the demonstration by Legge (1965) of changes in the variability and accuracy of matching on this task under N2O are indicative of changes in response bias and/or attention rather than perceptual sensitivity. It is argued that narcosis slows rather than distorts information processing. Slowing is accompanied by strategic changes that may be maladaptive. This suggests that, contrary to conventional wisdom, the safety and efficiency of divers exposed to narcosis could be improved with training.

Adult↗
PubMed1992

The effects of hypoxia on auditory reaction time and P300 latency.

A predominant feature of hypoxia is that it slows information processing. Evidence is accumulating that early visual mechanisms are an important locus of this slowing. Audition is believed to be insensitive to hypoxia, implying relatively less slowing with auditory stimuli. Subjects breathed air or a low oxygen mixture (65% arterial oxyhemoglobin saturation) while RT (reaction time) and the EEG were collected to oddball binaural tone pips at 500 Hz, 1000 Hz, and 4000 Hz. Hypoxia slowed RT and the event-related brain potential P300 in a correlated manner and by an identical amount that was generally independent of frequency. On the assumption that P300 indexes the time to evaluate a stimulus and RT indexes this time plus the time to select and execute a response, stimulus evaluation is implicated as a major locus of slowing in this experiment. The amount of slowing was comparable to that found previously with RT and P300 to visual stimuli. It may be that audition is more sensitive to hypoxia than is currently believed, at least where the speed of processing is concerned.

Adult↗
PubMed1992

The effects of hypoxia on components of the human event-related potential and relationship to reaction time.

This experiment investigated the relationship between the increase in reaction time (RT) caused by hypoxia and the P300, N200, P200 and N100 components of the event-related brain potential. Eight subjects breathed air or a low oxygen mixture (65% arterial oxyhemoglobin saturation) and RT was collected to visually presented stimuli at two levels of stimulus intensity while ERPs were recorded. An hypoxia x stimulus intensity interaction was found for RT, P300 latency and N200 latency. P200 latency and N100 latency were unaffected by hypoxia. These results were interpreted in terms of Additive Factors Method logic to indicate that the preprocessing stage of stimulus evaluation is slowed by hypoxia and that both P300 and N200 index this slowing.

Adult↗
PubMed1991

Renal heme metabolism in hereditary tyrosinemia: use of succinylacetone in rat renal tubules.

Succinylacetone (SA), a metabolic end-product found in urine from individuals with hereditary tyrosinemia and associated renal Fanconi syndrome and a known inhibitor of hepatic 5-aminolevulinic acid dehydratase (ALAD), has been used to study heme metabolism in isolated rat renal tubules. Heme biosynthetic porphyrin precursors are increased selectively in the presence of 4 mmol/1 SA. Total porphyrin content of the tubules are increased approximately 2-fold, while both ferrochelatase and heme oxygenase activities remain unaffected by SA. Nonetheless, total heme content is reduced, as was incorporation of radioactive label from amino[14C]levulinic acid. Cytochrome P-450 content remained unaffected. Impairment of iron uptake and/or transport within the cell or enhancement of heme catabolism via a non-heme oxygenase-dependent pathway could explain the observations.

Amino Acid Metabolism, Inborn Errors↗
PubMed1991

Hyperhomocysteinemia: an independent risk factor for vascular disease.

BACKGROUND: Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine beta-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine beta-synthase deficiency. METHODS: We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine beta-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0 mumol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The peak serum homocysteine levels in these normal subjects were then compared with those in 123 patients whose vascular disease had been diagnosed before they were 55 years of age. RESULTS: Hyperhomocysteinemia was detected in 16 of 38 patients with cerebrovascular disease (42 percent), 7 of 25 with peripheral vascular disease (28 percent), and 18 of 60 with coronary vascular disease (30 percent), but in none of the 27 normal subjects. After adjustment for the effects of conventional risk factors, the lower 95 percent confidence limit for the odds ratio for vascular disease among the patients with hyperhomocysteinemia, as compared with the normal subjects, was 3.2. The geometric-mean peak serum homocysteine level was 1.33 times higher in the patients with vascular disease than in the normal subjects (P = 0.002). The presence of cystathionine beta-synthase deficiency was confirmed in 18 of 23 patients with vascular disease who had hyperhomocysteinemia. CONCLUSIONS: Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency.

Cerebrovascular Disorders↗
PubMed1991

Determination of very-long-chain fatty acids in plasma by a simplified gas chromatographic-mass spectrometric procedure.

The concentration of very-long-chain fatty acids (VLCFA) (straight chain, more than 22 carbon atoms) in plasma or in cultured fibroblasts is one of the most important diagnostic criteria for the diagnosis of the peroxisomal disorders. A sensitive method for VLCFA assay in plasma, using small sample volume and a simplified procedure, is described. After adequate extraction and derivatization, methyl esters of VLCFA are separated, identificated and quantified by gas chromatography-mass spectrometry (GC-MS). The method is sensitive, reproducible, accurate and relatively simple. GC-MS equipment used for routine organic acid analysis can be used.

Fatty Acids↗
PubMed1991

The coordination of bimanual aiming movements: evidence for progressive desynchronization.

It is known that when simultaneous bimanual aiming movements are made to targets with different IDs (Index of Difficulty), Fitts' Law is violated. There is massive slowing of the easy target hand, but a debate has arisen over the degree of synchronization between the hands and whether this effect represents a coordinative structure or interference due to neural cross-talk. This issue was investigated in an experiment with 12 subjects who moved styli forward in the sagittal plane to pairs of targets that differed in difficulty (0.77/3.73 ID and 0.77/5.17 ID). Reaction time, movement time, and kinematic measures of resultant velocity and acceleration were analysed. The results showed clear-cut timing differences between the hands that depended on both the ID difference between target pairs and elapsed time of the movement. The violation of Fitts' Law was confined to the easy target hand. Pronounced individual differences in both timing differences and left-right asymmetry were also noted. Neither the coordinative structure nor the neural cross-talk models can fully account for these data, and it is possible that the initial constraints on movement are moderated by visually driven corrective movements.

Adolescent↗
PubMed1991

No sensory neuropathy during pyridoxine treatment in homocystinuria.

Seventeen patients with cystathionine synthase deficiency homocystinuria were examined clinically and neurophysiologically for evidence of sensory neuropathy. All had received high dose pyridoxine (vitamin B-6) for many years. Absence of neurological disturbance in all cases suggests long term treatment with pyridoxine in the dosages used in homocystinuric patients is not harmful.

Adolescent↗
PubMed1991

A health education program for inner city high school youths: promoting positive health behaviors through intervention.

This descriptive study examined the influence of a 7-week Health Education Program (HEP) on the reported health behaviors of inner city high school youths. A convenience sample of 83 youths between the ages of 14 and 17 years was selected from a moderate size, metropolitan, midwestern high school. A 32-item Health Behaviors Survey (HBS), developed by the researcher, was administered to the youths before and after the completion of the HEP. Participants were classified by their health behaviors into high-, moderate-, or low-risk categories. In addition, the subjects completed a health diary that was discussed before the weekly presentations. Findings of the study revealed a positive shift in several reported health behaviors from high-risk to low-risk following completion of the HEP. The professional nurse is in an excellent position to develop nursing interventions and creative innovations including preventive measures to positively influence the health behaviors of young people.

Adolescent↗