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Biomedical subjects

B Fowler

Publications and source records attributed to B Fowler.

At least 19 recordsLinked to original sources
PubMed2001

In vivo bone formation by human bone marrow stromal cells: effect of carrier particle size and shape.

Successful closure of bone defects in patients remains an active area of basic and clinical research. A novel and promising approach is the transplantation of human bone marrow stromal cells (BMSCs), which have been shown to possess a significant osteogenic potential. The extent and quality of bone formation by transplanted human BMSCs strongly depends on the carrier matrix with which cells are transplanted; to date, hydroxyapatite/tricalcium phosphate (HA/TCP) supports far more osteogenesis than any other matrix tested. In order to further improve the technique of BMSC transplantation, we studied whether commercially available HA/TCP particles, clinically approved as an osteoconductive material and commercially available as particles measuring 0.5-1.0 mm diameter, is an optimum matrix for promoting bone development by BMSCs. HA/TCP and HA particles of varying size were sieved into a variety of size ranges, from <0.044 mm to 1.0-2.0 mm. Transplants were formed by mixing 40 mg aliquots of particles with cultured passaged human BMSCs. They were placed in subcutaneous pockets in immunocompromised Bg-Nu-XID mice and harvested 4 or 10 weeks later. The transplants were examined histologically; the presence of bone within each transplant was evaluated using histomorphometry or blindly scored on a semiquantitative scale. Transplant morphology and the amount of new bone varied in a consistent fashion based on particle size and shape. Transplants incorporating HA/TCP particles of 0.1-0.25 mm size demonstrated the greatest bone formation at both 4 and 10 weeks; larger or smaller particles were associated with less extensive bone formation, while a size of 0.044 mm represented a threshold below which no bone formation could be observed. Flat-sided HA particles measuring 0.1-0.25 mm formed no bone. The differences in bone formation were not attributable to the differences in cell attachment among the groups. Instead, the size and spatial and structural organization of the particles within BMSC transplants appear to determine the extent of bone formation. These findings provide necessary information for the successful clinical application of BMSC transplantation techniques.

Animals↗
PubMed2001

Disturbed ratio of erythrocyte and plasma S-adenosylmethionine/S-adenosylhomocysteine in peripheral arterial occlusive disease.

Altered homocysteine metabolism associated with peripheral arterial occlusive disease (PAOD) may lead to impairment of vital methylation reactions through accumulation of S-adenosylhomocysteine (AdoHcy) as well as through alteration of the ratio S-adenosylmethionine (AdoMet)/AdoHcy. We determined AdoMet, AdoHcy, their ratio, and homocysteine in plasma as well as AdoMet, AdoHcy, and their ratio in erythrocytes of 61 patients with PAOD (age 49-93) and 50 healthy controls (age 41-87). Geometric mean values of plasma homocysteine, AdoMet, and AdoHcy were significantly increased in patients compared with controls (15.5 vs. 10.4 micromol/l**; 107 vs. 52.3* nmol/l; 55. 0 vs. 23.1** nmol/l, respectively; *P<0.01, **P<0.001), while the ratio of AdoMet/AdoHcy was decreased in patients (1.92 vs. 2.52*). In erythrocytes patients exhibited increased levels of AdoHcy compared with controls (309 vs. 205 nmol/l**) whereas AdoMet (3351 vs. 3732 nmol/l*) and the ratio of AdoMet/AdoHcy (11.8 vs. 19.1**) were decreased. The odds ratio (OR) for developing PAOD with decreased AdoMet/AdoHcy ratio after adjustment for kidney function was significant for erythrocyte levels < or =14.2 (OR, 7.1 (6.9-7.2, 95% CI). In addition, hematocrit levels were found to be significantly decreased in patients versus controls (0.35 vs. 0.42 l/l**) and were significantly correlated with the ratio of AdoMet/AdoHcy in erythrocytes of the patients. Since the ratio of AdoMet/AdoHcy is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients.

Adult↗
PubMed2001

The folate cycle and disease in humans.

The prevalence of hyperhomocysteinemia in renal disease patients, its treatment by folate administration, and its aggravation by the 677 C-->T mutation of methylene-tetrahydrofolate (methylene-THF) reductase has established the folate cycle as an important factor in the pathogenesis and management of renal disease. Proper function of the folate cycle depends on normal function of involved enzymes adequate of the vitamin and its correct disposition within the body. Vital processes in folate disposition include conversion of dietary folylpolyglutamates to monoglutamates, intestinal absorption, receptor and carrier-mediated transport across cell membranes, and cellular export. Folate coenzymes are responsible for the one-carbon unit transfer in intermediary metabolism and are required for several reactions in key metabolic processes, for example of purine, pyrimidine and methionine synthesis, and glycine and serine metabolism. Methionine synthase and its recently discovered reducing protein as well as methylene tetrahydrofolate reductase are key folate enzymes in homocysteine metabolism. Deficiencies of these enzymes are important causes of severe disease in the rare remethylation defects causing homocystinuria. Knowledge of their catalytic and molecular properties is important in understanding possible causes of moderate hyperhomocysteinemia, as for example, the well-known 677 C-->T transition of methylene tetrahydrofolate reductase.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2000

Homocystinuria in the Arab population of Israel: identification of two novel mutations using DGGE analysis.

This study describes, for the first time, a thorough genetic investigation in Israeli Arab homocystinuric patients. By using a DGGE methodology and sequencing we were able to identify the disease causing mutation in all. Of the mutations that were detected, two are novel: a 785C>G transversion in exon 7 (T262R) and a 5-bp deletion in the 5' of IVS17 including the T in the +2 position that is crucial for correct splicing (g18327-18331del5). In spite of the highly consanguineous nature of this population several different mutations were found. This may suggest that the mutations arose only recently in the population. The results of our study would enable early prenatal diagnosis, genetic counseling and screening for the mutations in population at risk. Hum Mutat 16:372, 2000.

Child↗
PubMed2000

Exercise for intermittent claudication.

BACKGROUND: Exercise is an inexpensive, low risk option compared with other more invasive therapies for leg pain on walking (intermittent claudication). OBJECTIVES: The objective of this review was to determine the effects of exercise for leg pain. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, Embase, reference lists of relevant articles, and contacted principal investigators of trials. SELECTION CRITERIA: Randomised trials of exercise regimens in patients with leg pain on walking (intermittent claudication). DATA COLLECTION AND ANALYSIS: At least two reviewers extracted and assessed data trial quality independently. The reviewers contacted investigators to obtain information or data needed for the review that could not be found in published reports. MAIN RESULTS: Fifteen trials were identified that met the inclusion criteria, but five were subsequently excluded because of poor quality. The remaining ten trials involved a total of almost 250 male and female patients with stable leg pain. The follow-up ranged from 12 weeks to 15 months. There was also some variation in the exercise regimens used, although all recommended at least two weekly sessions of, mostly, supervised exercise. All trials used a treadmill walking test as one of the outcome measures. The overall quality of the included trials was generally good, though the trials were all small (20-49 patients). Exercise therapy significantly improved maximal walking time (minutes) (weighted mean difference 6.51, 95% confidence interval 4.36 to 8.66, fixed effect model [FE]), with an overall improvement in walking ability of approximately 150% (range 74% to 230%). Exercise produced significant improvements in walking time compared with both angioplasty at six months (weighted mean difference 3.30, 95% confidence interval 2.21 to 4.39, FE) and antiplatelet therapy (weighted mean difference 1.06, 95% confidence interval 0.15 to 1.97, FE), and did not differ significantly from surgical treatment. In one small trial, exercise was less effective than pentoxifylline (weighted mean difference -0.45, 95% confidence interval -0.66 to -0.24, FE). REVIEWER'S CONCLUSIONS: Exercise is of significant benefit to patients with leg pain.

Exercise Therapy↗
PubMed2000

The determination of toxaphene in environmental samples by negative ion electron capture high resolution mass spectrometry.

A method is described for the analysis of toxaphene in environmental samples by high resolution gas chromatography high resolution mass spectrometry in selected ion electron capture negative ion mode. Toxaphene is detected by monitoring [M-Cl]- fragments ions of chlorobornanes (Cl6-Cl10) and chlorobornenes (Cl6-Cl7) using formal ion ratio criteria. The method shows high sensitivity and excellent specificity for the detection of chlorobornanes with negligible interference from of a wide range of common environmental organochlorines including chlordanes, PCBs and PCB-oxygen adducts. The analytical scheme is applicable to sediment and biological tissue samples and typically provide sample detection limits of less than 0.2 ng/g technical toxaphene for a 10 g sample.

Animals↗
PubMed2000

The exhaustive additivity displayed by nitrous oxide has implications for cognitive-energetical theory.

The cognitive-energetical approach, which relies on the discrete stage model of additive factors logic, asserts that basal energetical mechanisms such as arousal act via particular information processing stages. The anaesthetic gas nitrous oxide (N(2)O) produces additivity at four of the five perceptual and central stages, but its effect on the remaining stage, feature extraction, is unknown. We investigated this stage using 12 subjects who performed a visual oddball experiment in which two levels of stimulus quality, three levels of breathing mixture (air, 25% and N(2)O, 35%) and three levels of stimulus probability were combined factorially. Reaction time (RT) and P300 were collected simultaneously. The RT results showed additivity between N(2)O, stimulus quality and probability. P300 latency also showed additivity between N(2)O and stimulus quality. Since the discrete stage model cannot easily account for the exhaustive additivity displayed by N(2)O on perceptual and central stages, we performed a continuous cascade model simulation to determine whether it is better able to account for this phenomenon. We found that exhaustive additivity could be reproduced by adding a time delay to the activation rate of the first stage, which we interpreted as evidence that N(2)O causes slowing prior to stage processing. To account for these results, we propose a two-tiered energetical model in which a lower GABAergic reticular system (influenced by N(2)O) modulates the activity of upper 'arousal-like' multidimensional ascending thalamocortical systems. The applicability of this model to drugs such as the barbiturates, the benzodiazepines and ethanol, as well as the aging process, is discussed.

Adult↗
PubMed2000

Is dual-task performance necessarily impaired in space?

Recent single-subject experiments in space have reported impaired dual-task performance that could result from either a direct effect of microgravity on the central nervous system or from the multistressor environment. We sought to distinguish between these hypotheses using 6 astronauts in the 16-day NASA Neurolab mission, testing them at intervals with a dual task consisting of primary pursuit tracking without vision of the hand and secondary reaction time (RT). The participants were highly trained, instructed to maintain a fixed attention strategy, and restrained in the apparatus. The results showed that absolute and variable tracking error, as well as correct RT and the standard deviation of RT, were unimpaired. However, RT errors became more variable, an effect attributed to a decrease in strategic control. We conclude that the impairments observed in previous dual-task space experiments can be attributed to stressors rather than to microgravity and that performance deficits are probably not a necessary concomitant of space flight if attention is paid to task design and astronaut training.

Adult↗
PubMed2000

A review of cognitive and perceptual-motor performance in space.

Although a consensus developed early in the space program that complex operations could be performed successfully in space, it appears that humans are slower there than on Earth. Recent experiments aimed at determining the cause of this slowing suggest that central cognitive operations are unaffected but that perceptual-motor performance is degraded under certain circumstances. Two hypotheses have been proposed to account for this degradation-the direct effects of microgravity on the central nervous system and the non-specific effects of multiple stressors. Present evidence can be interpreted as supporting either hypothesis and further experiments are required to settle the question. This issue has practical implications since the countermeasures needed to ameliorate or prevent performance deficits will differ according to which hypothesis is correct. Understanding and ameliorating performance deficits will help ensure safe operations aboard the International Space Station and during a mission to Mars.

Cognition Disorders↗
PubMed2000

Summary of research issues in monitoring of mental and perceptual-motor performance and stress in space.

This article describes the papers presented in the workshop that cover the monitoring of stress and perceptual-motor performance. Monitoring is necessary for early detection and intervention of individual and group stress, especially on long-term missions. Test batteries will need to be developed that provide diagnostic information about the cause of deficits so that countermeasures can be applied.

Humans↗
PubMed2000

Hearing thresholds under acute hypoxia and relationship to slowing in the auditory modality.

BACKGROUND: Acute hypoxia slows reaction time to visual stimuli and it has been proposed that this slowing can be accounted for by a decrease in perceived brightness. Auditory slowing could be accounted for in an analogous manner if hypoxia decreases perceived loudness, as reflected by an increase in pure-tone thresholds. However, evidence concerning the effects of hypoxia on auditory thresholds is contradictory and we performed an experiment to clarify this issue. Pilot work suggested that thresholds were raised due to noise from our breathing apparatus used to deliver the low O2 mixtures and we eliminated this artifact by measuring thresholds while the subjects held their breath. METHODS: The six subjects breathed either air as a control through an oro-nasal mask or low O2 mixtures to maintain arterial blood oxygen saturation at 74% while thresholds between 500-4000 Hz were measured with an audiometer during breathholding. RESULTS: Hypoxia produced a statistically significant but practically insignificant decrease in thresholds of 1 dB across all frequencies tested. CONCLUSIONS: Our results are consistent with the view that audition is relatively insensitive to hypoxia and that the slowing observed with auditory stimuli cannot be accounted for by an increase in auditory thresholds. Some alternative hypotheses which could account for this slowing are proposed.

Adult↗
PubMed1999

Nigral endothelial dysfunction, homocysteine, and Parkinson's disease.

We found increased levels of atherosclerosis-inducing homocysteine in parkinsonian patients with long-term application of levodopa compared with previously untreated parkinsonian patients and controls. We conclude that antiparkinsonian treatment with levodopa promotes occurrence of vascular disease in Parkinson's disease.

Aged↗
PubMed1999

Pap smear screening among urban Southwestern American Indian women.

BACKGROUND: American Indian women have among the highest incidence and mortality rates of cervix cancer in the United States. The incidence of cancer of the cervix among American Indians is 19.5/100,000 versus 7.8/100,000 in U.S. whites, and comparison by geographic region/tribe indicates that the rate is four to six times higher in some tribes. Papanicolaou cytological testing (Pap smear) permits the detection of cervical lesions before they become cancerous, effectively reducing the incidence of cervical cancer by 75-90%. The American Cancer Society recommends a Pap smear every year beginning at age 18 years or when sexually active, and more frequent screening in high-risk populations. METHODS: A random household cross-sectional survey was conducted in Phoenix, Arizona, to assess cervical cancer screening rates among 519 adult urban American Indian women. Logistic regression was used to identify predictors of Pap smear use. RESULTS: Three-quarters (76.1%) of urban women American Indian surveyed received a Pap smear within the past 3 years, but only 49.5% received a Pap smear within the last year. Women over age 50 years were significantly less likely to have received a recent Pap smear in comparison to younger women. CONCLUSIONS: The results of this study indicate that limited access to health care and lack of knowledge about the procedure were important barriers to Pap smear use. Improving cervix cancer screening participation rates is an important step in reducing the disease burden in this high-risk population.

Adult↗
PubMed1999

Cancer prevention among urban southwestern American Indian women: comparison to selected Year 2000 national health objectives.

PURPOSE: The health issues which have historically faced American Indians are related to infectious disease, but today many chronic diseases play a large role in the health status of this special population. For example, existing data indicate that American Indians have the poorest cancer survival of any group in the U.S. (34% vs. 50% for U.S. Whites). Regular participation in cancer screening and lifestyle factors such as smoking, diet, and alcohol have been found to significantly contribute to cancer risk. However, available information about these behaviors is sparse and suffers from limitations. The purpose of this study was to assess the prevalence of cancer risk behaviors and provider recommendation for cancer screening among urban American Indian women. METHODS: A random household cross-sectional survey was administered to 519 adult American Indian women in Phoenix, Arizona. Smoking and weight status, alcohol consumption, physical activity, and provider referral were assessed by self-report. RESULTS: The results indicate that weight (69.6% were overweight) and excessive alcohol consumption (12.1 reported chronic drinking) were significant health issues in this population. The prevalence of provider referral for smoking cessation (14.9% among ever smokers) and breast as well as cervical cancer screening (30.1% and 55.5%, respectively) were below the 75% level set forth in the Year 2000 Goals. CONCLUSIONS: The results of this study suggest that increased cancer prevention and control efforts are needed in this special population to address the link between diet, weight, and long-term disease prevention.

Adult↗
PubMed1999

Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age.

BACKGROUND: Elevated fasting levels of total homocysteine are now accepted as an independent risk factor for the development of arteriosclerotic vascular diseases. A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), caused by the C677T point mutation, leads to increased thermolability of the enzyme, with reduced enzyme activity. We studied the frequency of this mutation in different groups of the Swiss adult population. PATIENTS AND METHODS: DNA from 361 subjects was screened for the thermolabile MTHFR variant with PCR. Included were healthy subjects without vascular disease (n = 118), older healthy subjects (n = 106), patients with coronary artery disease (CAD, n = 75), and patients with peripheral arterial occlusive disease (PAOD, n = 63). RESULTS: In the different groups studied, homozygosity for the mutation ranged from 4.8 to 16.2%, with a frequency of 16.2% in the healthy cohort. The allele frequencies of the thermolabile allele were 38.5 and 27.3 in young and old controls, and 37.3 and 33.3 in CAD and PAOD patients. In the healthy younger subjects the mutant allele was 1.4 times more frequent compared to the older subjects (P = 0.01). No difference in either MTHFR genotype distribution (P = 0.33) or allele frequencies (P = 0.48) between patients and controls was found. Except for the PAOD group with elevated tHcy levels for the +/+ carriers compared to the other genotypes, no statistically significant difference was found comparing homocysteine levels with genotype. CONCLUSION: This study shows no link between the mutation and the occurrence of vascular disease but we found evidence pointing to a correlation between the mutation and longevity in our population.

Adult↗
PubMed1999

Arsenic: health effects, mechanisms of actions, and research issues.

A meeting on the health effects of arsenic (As), its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Although arsenite [As(III)] can inhibit more than 200 enzymes, events underlying the induction of the noncarcinogenic effects of As are not understood. With respect to carcinogenicity, As can affect DNA repair, methylation of DNA, and increase radical formation and activation of the protooncogene c-myc, but none of these potential pathways have widespread acceptance as the principal etiologic event. In addition, there are no accepted models for the study of As-induced carcinogenesis. At the final meeting session we considered research needs. Among the most important areas cited were a) As metabolism and its interaction with cellular constituents; b) possible bioaccumulation of As; c) interactions with other metals; d) effects of As on genetic material; e) development of animal models and cell systems to study effects of As; and f) a better characterization of human exposures as related to health risks. Some of the barriers to the advancement of As research included an apparent lack of interest in the United States on As research; lack of relevant animal models; difficulty with adoption of uniform methodologies; lack of accepted biomarkers; and the need for a central storage repository for stored specimens.

Arsenic↗
PubMed1999

The influence of sizing on the dynamic function of the free-hand implanted porcine aortic homograft: an in vitro study.

BACKGROUND AND AIMS OF THE STUDY: The influence of sizing on the function of a porcine aortic valve after its implantation using the free-hand technique in the subcoronary position was investigated. METHODS: Dynamic function and leaflet configuration of the valve (n = 16) were first analyzed in its natural aortic root in a left heart simulator at 120/80 mmHg pressure and 4 l/min cardiac output. The valve was then implanted in the recipient porcine aortic root and re-studied. Three groups were investigated: group I (n = 4) comprised of 1-2 mm smaller donor aortic valve than the recipient; group II (n = 8) 3-4 mm smaller; and group III (n = 4) 5-7 mm smaller. Orifice area (OA), systolic and diastolic configurations of the leaflets, pattern and timing of leaflet opening and closure, commissural movement, pressure gradient and valvular regurgitation were analyzed. RESULTS: In the intact donor aortic root, average expansion of the aorta at the commissures, for a pressure change from 0 to 80 mmHg, was about 42%. This was reduced significantly in all assemblies. Group I showed a 34% reduction in OA, and excessive leaflet bending; there was no aortic insufficiency (AI) or pressure gradient across the valve. In group III there was a lesser reduction in OA and reduced leaflet bending, but two of four valves had AI. In group II, the reduction in OA was only 13%, there was less leaflet bending, and no AI. CONCLUSIONS: The donor valve 3-4 mm smaller than the recipient seems an optimal match. The current practice of using the same size donor as recipient may be responsible for excessive leaflet bending and may be implicated in early deterioration of the homograft.

Animals↗