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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 145 records · Page 8Linked to original sources
PubMed1999

Population distribution and effects on drug metabolism of a genetic variant in the 5' promoter region of CYP3A4.

BACKGROUND: There are large interindividual differences in CYP3A4 expression and in the metabolism of drug substrates for this enzyme. We and others have identified a polymorphism in the 5' promotor region of the CYP3A4 gene; however, its functional significance is not currently known. This study was conducted to determine whether this polymorphism plays a clinically important role in determining CYP3A4 phenotype. METHODS: An adenine (A) to guanine (G) transition was identified in the 5' promotor region of the CYP3A4 gene at position -292 (from the start codon), in a sequence motif known as the nifedipine-specific element. The frequency of this polymorphism was assessed in 802 healthy volunteers from five broadly defined racial groups. The population distribution of the G allele in these groups was as follows: white Americans (3.6%; n = 273), black Americans (54.6%, n = 186), Hispanic Americans (9.3%; n = 188), Japanese Americans (0.0%; n = 77), and Chinese Americans (0.0%; n = 78). In a subsequent study, 90 additional black Americans were genotyped, and a subset of the homozygous subjects (AA, n = 8; GG, n = 23) were given the CYP3A4 probe substrates erythromycin and nifedipine to allow genotype-phenotype comparisons to be made. RESULTS: There was no difference in the rate of CYP3A4-dependent demethylation of erythromycin (erythromycin breath test) or the pharmacokinetics of nifedipine or its CYP3A4-dependent metabolite dehydronifedipine between the two genotype groups (AA or GG). CONCLUSIONS: This promotor region polymorphism does not appear to play a major role in determining constitutive CYP3A4 expression.

Area Under Curve↗
PubMed1999

Gamma-aminobutyric acid (GABA) A and B receptors mediate the stimulatory effects of GABA on the human sperm acrosome reaction: interaction with progesterone.

OBJECTIVE: To evaluate which gamma-aminobutyric acid (GABA) receptor mediates the stimulatory effects of this neurotransmitter on the human sperm acrosome reaction, and to examine the interaction of progesterone, a physiologic inducer of the acrosome reaction, with the GABA(A) receptor. DESIGN: Prospective study. SETTING: A university clinic of andrology. PATIENT(S): Men with normal sperm analysis parameters. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The acrosome reaction of motile spermatozoa. RESULT(S): The acrosome reaction was stimulated by GABA in a dose-dependent manner. This effect was inhibited completely by bicuculline, a GABA(A) receptor antagonist, and only partially by saclofen, a GABA(B) receptor antagonist. Accordingly, muscimol, a GABA(A) receptor agonist, stimulated the acrosome reaction to the same extent as GABA, whereas baclofen, a GABA(B) receptor agonist, was less effective. Preincubation with progesterone followed by the addition of GABA resulted in a significant increase in the percentage of acrosome-reacted spermatozoa compared with progesterone alone. However, this increase was less than a simple addition of effects, suggesting that GABA and progesterone act through the same receptor and/or use the same mechanism of action. To test this hypothesis, the ability of progesterone to induce acrosome reaction was tested in the presence of bicuculline, which suppressed the stimulatory effects of progesterone. Given that the GABA(A) receptor is linked to the chloride channel, we tested whether picrotoxin, a blocker of this channel, could modulate the effects of progesterone or GABA. Picrotoxin completely suppressed the acrosome reaction induced by progesterone and only partially suppressed that caused by GABA. CONCLUSION(S): gamma-Aminobutyric acid stimulated the acrosome reaction in human spermatozoa, acting mainly through the GABA(A) receptor and to a lesser extent through the GABA(B) receptor. Progesterone interacted with the GABA(A) receptor to induce the acrosome reaction, and the functional integrity of the chloride channel was vital for this effect.

Acrosome↗
PubMed1999

Cellular responses to radiation and risk of breast cancer.

Mutations in the ataxia telangiectasia gene (ATM) result in an abnormal p53-mediated cellular response to DNA damage produced by ionising radiation. This deficiency is believed to contribute to the radiosensitivity and high cancer risk seen in ataxia telangiectasia (AT) patients and AT heterozygotes. Epidemiological studies have demonstrated that relatives of AT patients are particularly predisposed to breast cancer. This observation, together with the finding that a relatively high proportion of breast cancer patients display an abnormal severe reaction of normal tissues following radiotherapy, has led to the suggestion that AT heterozygosity plays a role in radiosensitivity and breast cancer development. The cloning of the ATM gene has allowed this possibility to be examined at the molecular level. The studies reported to date remain inconclusive, with the number of AT heterozygotes being found in radiosensitive breast cancer patients being less than would be expected based on the family studies. The potential role of several other recently identified genes which are involved in the cellular DNA damage response to ionising radiation and which could also play a role in radiosensitivity and breast cancer development are reviewed.

Ataxia Telangiectasia↗
PubMed1999

Radiation, DNA damage and cancer.

The characterization of the rare, radiation-sensitive and cancer-prone syndromes, ataxia telangiectasia and Nijmegen breakage syndrome, has demonstrated that genetic predisposition increases the risk of developing cancer after exposure to ionizing radiation (IR). Molecular analyses of these disorders provide valuable insights into the normal function of these two gene products in the cellular response to IR-induced DNA damage. Their contribution to a cellular radiosensitive phenotype and their role in sporadic cancers can now be fully assessed. For example, the gene ataxia telangiectasia mutated (ATM) has recently been shown to be a tumour suppressor gene in T-cell prolymphocytic leukaemia, and there is increasing evidence that individuals with one mutated ATM or Nijmegen breakage syndrome (NBS1) allele have an increased predisposition to cancer.

Ataxia Telangiectasia↗
PubMed1999

Chemical treatment of machined titanium surfaces. An in vitro study.

Microbial plaque accumulation on titanium dental implant surfaces can result in an inflammatory condition of the surrounding tissues. Cleaning of such a contaminated surface, in vivo, by means of a solution of amino-alcohol, following surgical exposure, has been proposed. However, the tissue healing following treatment resulted in formation of a fibrous capsule at the tissue-implant interface, i.e. improper implant re-integration. The present experiment was designed to investigate the possible influence of an amino-alcohol solution on machined titanium surface properties. Titanium samples with topography and chemical composition similar to the clinically used Brånemark implant surfaces were used in this experimental in-vitro study to investigate the adsorption of amino-alcohol to such surfaces, and the possibilities to chemically remove the adsorbed alcohols in order to recover a pristine titanium surface. The amino-alcohol solution was supplied to the sample surfaces and four different methods were subsequently used in order to remove the adsorbed alcohol molecules. It was shown that rinsing in water, saline solution, and 5% H2O2 did not remove the amino-alcohol from the surface. However, exposure to ozone produced by using a commercial mercury lamp in ambient air resulted in complete removal of the adsorbed amino-alcohol. The results show that the amino-alcohol used forms a stable and dense film at the implant surface in vitro. Presence of such a film most likely prevents re-integration to occur at the implant-tissue interface in vivo.

Adsorption↗
PubMed1999

Inbreeding depression and partial selfing: evolutionary implications of mixed-mating in a coastal endemic, silene douglasii var. oraria (Caryophyllaceae)

Recent studies have found moderate to high levels of selfing in plants despite high inbreeding depression. Because both factors influence the evolution and persistence of rare plants, we conducted glasshouse and field studies of pollination and inbreeding in Silene douglasii var. oraria, a perennial tetraploid endemic to coastal prairies. We detected: (i) variation in reproduction or inbreeding depression among life stages, years and maternal families; (ii) partial selfing yet higher relative fitness in outcrossed than selfed progeny; (iii) differing values of selfing and inbreeding depression using population means vs. matched maternal families. Fruit and seed production varied significantly with pollination treatment and year in flowers manipulated in situ during three seasons of growth. Hand-pollinations providing pollen in excess of ovule production in 1996 yielded more seeds than marked, open-pollinated flowers, implying pollen limitation of seed production. However, among-year differences in reproductive success after open-pollination (i.e. values equivalent to autogamy, selfing or outcrossing) suggest that pollination levels also vary temporally. In pollinations matched by maternal family, selfing yielded significantly fewer seeds than outcrossing. Fitness differences between inbred and outbred progeny were significant (P < 0.05) for seed production, percentage germination, and biomass or fecundity, but not for survival. Maternal family data gave selfing rates intermediate between obligate outcrossers and predominant selfers (S = 0.34-0.51), but population-wide means gave unusually high values (S = 1.1-1.6). Cumulative inbreeding depression was 76% for maternal families, and 70-85% using population means; in all cases, inbreeding depression values were high in early and late life stages, and lowest for survival. Thus far, reproductive assurance offers the most cogent explanation for the coexistence of moderate selfing and high inbreeding depression in this strongly protandrous Silene once thought to be highly outcrossing. This possibility merits further study in other rare plants with mixed-mating systems, where inbreeding depression and pollinator scarcity may both compromise population persistence and raise the threshold below which selfing is favoured by evolution.

Journal Article↗
PubMed1999

Effect of a standard exercise protocol on shoulder pain in long-term wheelchair users.

PURPOSE: To analyze the effectiveness of a 6-month exercise protocol on shoulder pain experienced by wheelchair users during functional activities. SUBJECTS: Forty-two wheelchair users, 35 males and seven females: average age of 35 years and an average duration of wheelchair use of 14 years. METHODS: Subjects were randomly assigned to treatment (n=21) and control (n=21) groups. The treatment group received instruction in five shoulder exercises which they performed daily for 6 months. The exercise protocol included two exercises for stretching anterior shoulder musculature and three exercises for strengthening posterior shoulder musculature. OUTCOME MEASURES: All subjects completed a self-report questionnaire and the Wheelchair Users Shoulder Pain Index (WUSPI) initially and at bimonthly intervals during the 6-month intervention. RESULTS: Seventy-five per cent of the subjects reported a history of shoulder pain since beginning wheelchair use. The average initial performance-corrected (PC-WUSPI) score of the 42 subjects was 17.7 (+/-21.3) with a range of 0-103.2 points. Over 83% of the subjects (35 of 42) completed the 6-month study. Subjects in the treatment group decreased their PC-WUSPI score by an average of 39.9%, compared to decreases of only 2.5% in the control group. CONCLUSIONS: These findings supported the effectiveness of this exercise protocol in decreasing the intensity of shoulder pain which interferes with functional activity in wheelchair users.

Adult↗
PubMed1999

A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort.

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation, typically starting in early adulthood. IBD is subdivided into two subtypes, on the basis of clinical and histologic features: Crohn disease and ulcerative colitis (UC). Previous genomewide searches identified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16. To expand our understanding of the genetic risk profile, we performed a 9-cM genomewide search for susceptibility loci in 268 families containing 353 affected sibling pairs. Previous linkages on chromosomes 12 and 16 were replicated, and the chromosome 4 linkage was extended in this sample. New suggestive evidence for autosomal linkages was observed on chromosomes 1, 6, 10, and 22, with LOD scores of 2.08, 2.07, 2.30, and 1.52, respectively. A maximum LOD score of 1.76 was observed on the X chromosome, for UC, which is consistent with the clinical association of IBD with Ullrich-Turner syndrome. The linkage finding on chromosome 6p is of interest, given the possible contribution of human leukocyte antigen and tumor necrosis-factor genes in IBD. This genomewide linkage scan, done with a large family cohort, has confirmed three previous IBD linkages and has provided evidence for five additional regions that may harbor IBD predisposition genes.

Cohort Studies↗
PubMed1999

Clonidine and cardiac surgery: haemodynamic and metabolic effects, myocardial ischaemia and recovery.

Clonidine may have beneficial effects in patients undergoing major surgery. We enrolled 156 patients having elective CABG surgery in a double-blind, randomized trial. Patients were randomized to receive either two doses of placebo (Group PP) or clonidine 5 micrograms/kg (Group CC). Perioperative measurements included haemodynamics, anaesthetic and analgesic drug usage, creatinine clearance, cortisol excretion, recovery times and quality of life (SF-36) after surgery. Overall, there was no significant difference with time to tracheal extubation (median [10-90 centile]): CC 7.1 (3.4-18) h vs PP 8.0 (4.3-17) h, P = 0.70; but there was a higher proportion of patients extubated within four hours: CC 20% vs. PP 8%, P = 0.038. Clonidine resulted in a number of significant (P < 0.05) haemodynamic changes, particularly pre-CPB: less tachycardia and hypertension, more bradycardia and hypotension. Clonidine was associated with a significant (P < 0.05) reduction in anaesthetic drug usage, higher creatinine clearance, lower cortisol excretion and improvement in some aspects of quality of life. This study lends support to consideration of clonidine therapy in patients undergoing CABG surgery.

Adrenergic alpha-Agonists↗
PubMed1999

Role of opticare eye drop delivery system in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the prevalence of keratoconjunctivitis sicca in 340 patients with rheumatoid arthritis undergoing outpatient followup, and to assess their ability to use artificial tears, and the role of an aid to dispensing drops, the Opticare. METHODS: Initial questionnaire given to 340 patients based on preliminary criteria for classification of Sjögren's syndrome. Thirty symptomatic patients were invited to undergo objective and subjective assessment of the ability to instill artificial tears with and without the Opticare. RESULTS: One hundred twenty-seven (37%) patients had had symptoms lasting at least 3 months at some time, and 85 (25%) were currently symptomatic. Many patients found difficulty using artificial tears due to problems aiming and squeezing the bottles as a result of impaired upper limb function. The Opticare statistically significantly improved the ability to squeeze out drops and get them in the eye. CONCLUSION: The Opticare device allows patients with functional impairment of the upper limb to instill artificial tears, resulting in less wastage of tears and increased independence and compliance.

Adult↗
PubMed1999

Verbal fluency in children: developmental issues and differential validity in distinguishing children with attention-deficit hyperactivity disorder and two subtypes of dyslexia.

Previous research studies have shown that in adults, verbal fluency is impaired after lesion to the frontal lobes and left temporal lobe. More recently, there have been a few studies reported which indicated that in children, like adults, left hemisphere and frontal lesions result in pronounced effects on verbal fluency. The present study examined developmental differences in verbal fluency within a sample of 130 normal children, aged 6 to 12 years. Additionally, the same verbal fluency test was administered to two subgroups of children with developmental dyslexia and a group of children with attention-deficit/hyperactivity disorder (ADHD). Analysis of variance (ANOVA) revealed significant between-group differences by age in the normal children. Further, ANOVA demonstrated that the verbal fluency measure was clinically useful in differentiating the Language Disorder/Dysphonetic Dyslexic subgroup from the Visual-Spatial/Dyseidetic Dyslexic subgroup and the ADHD group, with the latter two groups performing within the average range.

Journal Article↗
PubMed1998

Comparison of potency of inhaled beclomethasone and budesonide in New Zealand: retrospective study of computerised general practice records.

OBJECTIVE: To determine whether inhaled budesonide and beclomethasone are equipotent in the treatment of asthma in primary care. DESIGN: Retrospective study of computerised clinical records from 28 general practices in New Zealand. SUBJECTS: 5930 patients who received 16 725 prescriptions for inhaled budesonide or beclomethasone from 1 July 1994 to 30 June 1995. SETTING: General practices on the database of the Royal New Zealand College of General Practitioners Research Unit. Linked information from secondary care was available for a subset of the practices. MAIN OUTCOME MEASURE: Mean prescribed daily inhaled corticosteroid dose. RESULTS: The daily prescribed dose was higher for patients receiving inhaled budesonide (mean 979 microg) than beclomethasone (mean 635 microg), a difference of 344 microg (95% confidence interval 313 to 376 microg). This difference was consistent in all age bands and with different types of inhalation device. Evidence of systematic prescribing of higher doses of budesonide to patients with more severe asthma was not found. CONCLUSIONS: In primary care in New Zealand evidence suggests that budesonide is less potent than beclomethasone. Consideration of validated, established, and other possible markers of asthma severity did not support confounding by severity as a reason for the higher prescribed doses of budesonide. Pending further epidemiological evaluation, international asthma guidelines may need to be modified on the equivalence of inhaled corticosteroid doses. Furthermore, the comparative potency of newly developed inhaled steroids in clinical trials will need to be confirmed in appropriately designed epidemiological studies based in general practice.

Administration, Inhalation↗
PubMed1998

Urinary excretion of 5-(hydroxymethyl) uracil in healthy volunteers: effect of active and passive tobacco smoke.

The urinary excretion of 5-(hydroxymethyl)uracil (5-HMUra), one of the major oxidative modifications of thymine, was investigated in 134 healthy volunteers living in North Italy. Overnight urine was collected, and a questionnaire was completed on smoking habits and exposure to environmental tobacco smoke (ETS). 5-HMUra was analyzed by GC/MS, following urine purification by HPLC. 5-HMUra excretion showed an approximately normal distribution, ranging from 0.08 to 0.84 (mean 0.44) nmoles/kg/8 hr and from 3.2 to 18.7 (mean 8.5) nmoles/mmoles creatinine. 5-HMUra excretion was significantly higher in women than in men and in smokers than in non-smokers when results were expressed as the ratio to creatinine. Slightly higher levels of 5-HMUra excretion, expressed as nmoles/mmoles creatinine, were also found in subjects highly exposed to ETS, monitored either as the number of hours of exposure or as the number of smokers in the workplace and at home. Our results show that the urinary excretion of 5-HMUra is higher than that of other oxidized nucleobases, including 8-oxo-7,8-dihydroguanine, and can be slightly modified by environmental factors such as tobacco smoke. These findings suggest that measurement of urinary excretion of 5-HMUra could be useful as a biomarker of oxidative DNA damage and repair, though further research is needed to support these data.

Adult↗
PubMed1998

What is the role of mechanical bowel preparation in patients undergoing colorectal surgery?

BACKGROUND: Most surgeons use mechanical bowel preparation before performing operations on the colon and rectum. The aim of this study is to determine if there is any published literature that supports this practice. METHODS: We undertook a review of the literature on the benefits of mechanical bowel preparation in patients undergoing surgery on the colon and rectum. A meta-analysis was conducted on all available clinical trials addressing this issue. RESULTS: A meta-analysis of three clinical trials revealed a significantly greater incidence of wound infection in patients who received a mechanical bowel preparation (10.8 vs. 7.4 percent; P < 0.002; 95 percent confidence interval of the difference, -1.6-8.4 percent). Patients who received mechanical bowel preparation had an incidence of anastomotic leakage that was twice that of control patients; however, this difference was not significant (8.1 vs. 4 percent; P < 0. 1 14; 95 percent confidence interval of the difference, -0.4-8.4 percent). CONCLUSION: There is limited evidence in the literature to support the use of mechanical bowel preparation in patients undergoing colorectal surgery. Hence, there is a need for clinical trials comparing the more traditional, aggressive forms of bowel preparation (e.g., polyethylene glycol solutions, sodium phosphate) with either no preparation or simpler techniques, such as a single phosphate enema.

Colon↗
PubMed1998

Cardiorespiratory responses to underwater treadmill walking in healthy females.

This study compared the cardiorespiratory responses of eight healthy women (mean age 30.25 years) to submaximal exercise on land (LTm) and water treadmills (WTm) in chest-deep water (Aquaciser). In addition, the effects of two different water temperatures were examined (28 and 36 degrees C). Each exercise test consisted of three consecutive 5-min bouts at 3.5, 4.5 and 5.5 km x h(-1). Oxygen consumption (VO2) and heart rate (HR), measured using open-circuit spirometry and telemetry, respectively, increased linearly with increasing speed both in water and on land. At 3.5 km x h(-1) VO2 was similar across procedures [chi = 0.6 (0.05) l x min(-1)]. At 4.5 and 5.5 km x h(-1) VO2 was significantly higher in water than on land, but there was no temperature effect (WTm: 0.9 and 1.4, respectively; LTm: 0.8 and 0.9 l x min(-1), respectively). HR was significantly higher in WTm at 36 degrees C compared to WTm at 28 degrees C at all speeds, and compared to LTm at 4.5 and 5.5 km x h(-1) (P < or = 0.003). The HR-VO2 relationship showed that at a VO2 of 0.9 l x min(-1) x HR was higher in water at 36 degrees C (115 beats x min[-1]) than either on land (100 beats min[-1]) or in water at 28 degrees C (99 beats x min[-1]). The Borg scale of perceived exertion showed that walking in water at 4.5 and 5.5 km x h(-1) was significantly harder than on land (WTm: 11.4 and 14, respectively; LTm: 9.9 and 11, respectively; P < or = 0.001). These cardiorespiratory changes occurred despite a slower cadence in water (the mean difference at all speeds was 27 steps/min). Thus, walking in chest-deep water yields higher energy costs than walking at similar speeds on land. This data has implications for therapists working in hydrotherapy pools.

Adult↗