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Biomedical subjects

B Fowler

Publications and source records attributed to B Fowler.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1990

P300 latency indexes nitrogen narcosis.

This experiment investigated the effects of nitrogen narcosis on reaction time (RT) and P300 latency and amplitude. Ten subjects breathed either air or a non-narcotic 20% oxygen-80% helium (heliox) mixture in a hyperbaric chamber at 6.5, 8.3 and 10 atmospheres absolute (ATA). The subjects responded under controlled accuracy conditions to visually presented male or female names in an oddball paradigm. Single-trial analysis revealed a strong relationship between RT and P300 latency, both of which were slowed in a dose-related manner by hyperbaric air but not by heliox. A clear-cut dose-response relationship could not be established for P300 amplitude. These results indicate that P300 latency indexes nitrogen narcosis and are interpreted as support for the slowed processing model of inert gas narcosis.

Adult↗
PubMed1989

Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade.

Tissue factor (TF) is the high-affinity receptor for plasma factors VII and VIIa. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. Outside the vasculature, TF expression is highly dependent upon cell type. TF can also be induced by inflammatory mediators to appear on monocytes and vascular endothelial cells as a component of cellular immune responses. As an initial step toward elucidating the regulatory regions involved in control of TF gene expression, we have established the organization of the 12.4 kbp human TF gene and its complete DNA sequence. There are six exons separated by five introns. Within intron 5, we have mapped the single nucleotide difference which leads to the previously described MspI polymorphism; the same intron also contains an apparently polymorphic PstI site. The TF gene also contains three full-length Alu repeats and one partial Alu repeat. A single major transcription start site was identified 26 bp downstream from a TATA consensus promoter element. The putative promoter and first exon are located within a 1.2 kbp region of very high G + C content which fits the criteria of an HTF island. A cluster of predicted binding sites for a number of known transcription factors was found to coincide with this putative promoter region. These factors included AP-1 and AP-2 which can mediate the effects of phorbol esters, agonists known to induce TF expression in monocytes and vascular endothelial cells.

Amino Acid Sequence↗
PubMed1989

Chorionic villus sampling: diagnostic uses and limitations of enzyme assays.

Control ranges for enzymes in uncultured chorionic villi were established, based on: (1) 21 of 22 enzymes (mainly lysosomal) in villi had similar properties to the enzyme in cultured fibroblasts; (2) isoenzyme patterns in villi were similar to those in fibroblasts for five lysosomal enzymes but different for aryl sulphatases; (3) control ranges were determined for 12 enzymes in abortion villi and for 21 enzymes in biopsy villi, values tending to be higher in the latter for those enzymes studied in both types of sample; (4) storage of samples under various conditions revealed no major changes in activity of seven lysosomal enzymes. A number of potential pitfalls in the use of chorionic villus samples for diagnosis of metabolic disorders by enzyme assay are described: (1) the presence of aryl sulphatase C in chorionic villi, an isoenzyme which may interfere in assays of aryl sulphatase A; (2) the presence of maternal enzyme in chorionic villus material illustrated by the detection of the A isoenzyme of B-hexosaminidase in chorionic villus from a pregnancy affected with Sandhoff's disease; (3) the finding of falsely normal levels of alpha-iduronidase in chorionic villus samples from a pregnancy affected with Hurler's disease, probably due to contamination with maternal tissue which has relatively high levels of this enzyme compared with fetal chorionic material: (4) the inadequacy of indirect assays of incorporation of radiolabel into macromolecules using chorionic villi, for example [14C]propionate incorporation for prenatal diagnosis of methylmalonic aciduria. Provided that such pitfalls are recognized and great care is taken in selection of villus samples and interpretation of results, chorionic villus sampling allows reliable prenatal diagnosis of a large number of disorders using enzyme assays.

Chorionic Villi Sampling↗
PubMed1989

The effects of hyperbaric air in combination with ethyl alcohol and dextroamphetamine on serial choice-reaction time.

The effects of ethyl alcohol (1.5 ml/kg body weight) and dextroamphetamine (15 mg) on nitrogen narcosis were investigated in two experiments using a 2-, 3- and 4-choice serial reaction time (RT) task with accuracy held constant. Narcosis was induced with air at 6.4 atmospheres absolute (ATA) and a heliox mixture was used as a control. Heliox at 6.4 ATA did not affect RT. Alcohol alone and air at 6.4 ATA increased the intercept of the Hick-Hyman function whereas amphetamine alone decreased it. The increased intercept with air at 6.4 ATA was exacerbated additively by alcohol and ameliorated antagonistically by amphetamine. The slope of the Hick-Hyman function was unaffected. Frequency distributions were shifted as a whole and their shapes were unaltered. It is concluded that these data are consistent with the slowed processing model which proposes that the effects of narcosis on performance are due to a decrease in arousal in conjunction with secondary changes in task strategy.

Adult↗
PubMed1989

Narcosis has additive rather than interactive effects on discrimination reaction time.

A central feature of the impairment in performance produced by inert gas narcosis, which poses a threat to divers breathing compressed air, is a slowing of reaction time (RT). To investigate the locus of this slowing, the effects of 35% nitrous oxide on Crossman's confusion function were determined using line-length and weight discrimination tasks, with accuracy held constant. For both tasks narcosis slowed RT by increasing the intercept rather than the slope of Crossman's function. These results are interpreted in terms of additive factors method logic as being consistent with the predictions of the slowed processing model that has been proposed to account for the effects of narcosis on human performance.

Confusion↗
PubMed1989

Nitrogen narcosis and ethyl alcohol increase the gain of the vestibular ocular reflex.

The effects of air, helium-oxygen (6.4 ATA), and ethyl alcohol (40% by volume at a dose of 1.5 ml/kg body weight) were examined on the gain, number of beats, and phase lag of the vestibular ocular reflex (VOR) by means of electronystagmography (n = 7). It was found that hyperbaric air and alcohol, both alone and in combination, produced approximately the same increase in the velocity of the slow phase component of the nystagmus, thereby elevating the gain of the system to unity. Hyperbaric helium-oxygen did not influence the gain. These findings suggest that nitrogen nacrosis differentially impairs the system controlling the VOR. It is proposed that this impairment may help to explain the disorientation sometimes associated with nitrogen narcosis.

Adult↗
PubMed1988

First trimester prenatal diagnosis of Sandhoff's disease.

Chorionic villus sampling was performed on two patients with a previous family history of Sandhoff's disease. Total beta-hexosaminidase (Hex) activity in case 1 was within the normal range (case 1: 6365 mumol/h/g protein; control range: 3227-24 495 mumol/h/g protein). The beta-hexosaminidase isoenzyme pattern was found to be normal. These results were confirmed on cultured amniotic fluid cells. In case 2, the total Hex activity was 672 mumol/h/g protein, i.e., 7 per cent of the control mean (10,085 mumol/h/g protein), and chromatography demonstrated that more than 50 per cent of this activity was due to the abnormal isoenzyme beta-hexosaminidase S (Hex S). The fetus was predicted to be affected by Sandhoff's disease and this was confirmed on fetal tissues after termination of pregnancy. This study demonstrates that a fetus affected by Sandhoff's disease can be reliably diagnosed during the first trimester of pregnancy.

Adult↗