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Biomedical subjects

J T Wilson

Publications and source records attributed to J T Wilson.

At least 73 records · Page 4Linked to original sources

The detection of Hind III restriction-fragment length polymorphisms using a deoxyribonucleic acid probe for the beta subunit of follicle-stimulating hormone.

Molecular diagnosis of disorders of follicle-stimulating hormone (FSH) production may become possible now that the gene for FSH beta has been characterized. Restriction-fragment length polymorphism (RFLP) analysis provides a means of organized search for molecular variants of FSH. The purpose of this study was to screen controls for the presence of RFLPs using the deoxyribonucleic acid (DNA) probe pFSH beta -1.4. Genomic DNA was digested with 12 different restriction endonucleases; Southern blots were constructed and hybridized to pFSH beta -1.4. No polymorphisms were identified with 11 enzymes. Three of 24 (12.6%) Hind III digests demonstrated a polymorphic fragment of either 5.2, 4.7, or 4.3 kb. These are the first RFLPs identified for the FSH beta gene with pFSH beta -1.4. RFLPs for FSH beta constitute the first step in the molecular analysis of disorders of FSH production.

Blotting, Southern↗

Flurbiprofen in post-partum women: plasma and breast milk disposition.

The plasma and milk disposition of flurbiprofen (FB) was assessed in healthy women during the early post-partum period after multiple doses of FB. The results confirmed that a pragmatic study design is an attainable requirement for definitive statements about the excretion of FB in transitional milk. Nine doses of FB (50 mg per dose) were administered during three days. Paired milk and plasma samples were obtained during this period of dosing as well as after the last dose. The plasma data were used to derive an equation, which was then used to simulate cumulative plasma profiles for multiple doses given at unequal time intervals. The observed data corresponded to the simulated cumulative profiles of FB in plasma. The plasma elimination half-life of FB during early lactation was slightly prolonged (mean 4.8 hrs) as compared to reported values for normal adult men. The peak plasma concentrations of FB were comparable to those reported for healthy volunteers. In 10 of 12 women (3-5 days post-partum) the FB concentration in breast milk was less than 0.050 micrograms/ml. In two women the milk concentrations of FB were 0.06, 0.07 and 0.07 micrograms/ml as found in only three samples. We conclude that, on the basis of dose found in milk, FB is safe for women breast feeding their infants in the early post-partum period.

Adult↗

Profile of clinical pharmacologists in the United States.

The need for clinical pharmacology in research and education, drug development, and health care delivery is well known. However, a current profile of those working in the field is not available. The ACCP authorized a survey of clinical pharmacologists to provide such a profile. Members of the ACCP or ASCPT were solicited by mail with a self-assessment questionnaire. A response rate of 37% was obtained. Demographic findings agree well with a previous study2 limited to those with the M.D. Our results reveal that most clinical pharmacologists are between 30-59 years of age, have an MD, PhD or PharmD degree; most of those with MDs list their primary specialty as internal medicine, pediatrics, psychiatry, or anesthesiology. They affiliate with the respective departments (including pharmacology) in academia or hold positions in industry or government, but few are in clinical therapeutics per se. About 20% of those with only a MD or PharmD degree cite employment in health care delivery. However, a higher percentage of these respondents work in research and education rather than in drug development or health care delivery. For those with only a PhD, more work in drug development and research and education than in health care delivery. The highest proportion of respondents with any doctoral degree work in the Northeast. The average income is a function of rank, doctoral degree, specialty, department appointment, and type and location of employer. The profile of a typical clinical pharmacologist is presented. An analysis of clinical pharmacology manpower from several perspectives reveals a marked deficit, but the field itself is professionally and economically attractive. Lack of a well defined career track in academia and a poorly defined clinical role for MD clinical pharmacologists are proposed as reasons limiting entry of trainees. These and other results of the survey support an increased emphasis on training programs. Clinical pharmacologist involvement in health care delivery and drug development must be increased if the safe and effective use of new drugs is to be realized. Nine assessments and initiatives are formulated to accomplish this goal within the next decade.

Adult↗

Effects of dental medicaments on examination glove permeability.

Dental care providers wear gloves for all clinical procedures. This study was designed to assess the intactness of examination gloves after exposure to commonly used agents. Finger portions from latex and vinyl examination gloves were sealed to syringe barrels and exposed to alcohol, eugenol, a surface disinfectant, cavity varnish, or commercial mouth wash. Tritiated water was introduced into the finger-tip portion, which was suspended in a vacuum flask containing distilled water. Aliquots of water were withdrawn from the flask at intervals of 5 minutes to 8 hours and analyzed for transfer of radioactivity through the glove tip. Treatment with agents such as eugenol and cavity varnish resulted in significant leakage after 5 to 15 minutes. Although some agents apparently quickly damaged the gloves, leaks developed in untreated gloves with time. Results suggest that visibly intact gloves may have developed microleaks and that changing gloves during long clinical procedures may be indicated.

Dental Cavity Lining↗

Synthetic pyrethroid resistance in field samples in the cattle tick (Boophilus microplus).

First evidence of resistance to synthetic pyrethroids in the cattle tick in Australia, other than the pre-existing cross-resistance in DDT-resistant ticks, has emerged. Three new strains have been investigated and characterised. The first, detected in central Queensland, showed increased ability to detoxify pyrethroids resulting in a marginal loss of efficacy of all pyrethroid tickicides tested, except flumethrin. Subsequently two more strains have been detected, with serious implications for chemical tick control. The first, from southern Queensland, has a high level of specific resistance to flumethrin. The second, from central Queensland, has a broad spectrum resistance encompassing all pyrethroids currently in use. The toxicology and biochemistry of these new resistant strains have been investigated and alternative tickicides evaluated. The significance of these latest developments is discussed.

Animals↗

Renal handling of beta 2-microglobulin in patients with cystic fibrosis.

We evaluated the renal handling of beta 2-microglobulin (beta 2-M) and creatinine in healthy outpatients (n = 6), normal children hospitalized for infections treated with antibiotics (not including an aminoglycoside) (n = 4); outpatients with cystic fibrosis (CF; n = 12), and hospitalized patients with CF (n = 6) who received a 10- to 14-day course of antibiotic treatment that included an aminoglycoside. The serum beta 2-M concentrations in the normal outpatients (2020.1 +/- 276.6 micrograms/L) were significantly lower (p less than 0.05) than those observed for outpatients (2833.3 +/- 202.6 micrograms/L) or patients with CF (2861.8 +/- 340.5 micrograms/L. There were no significant differences found for creatinine clearance or fractional excretion of beta 2-M when subjects without CF were compared with those with the disease. Furthermore, no significant differences were observed in hospitalized patients with CF when creatinine clearance and fractional excretion of beta 2-M were compared between the initiation and conclusion of aminoglycoside treatment. Glomerular filtration and proximal tubular reabsorption of beta 2-M were not altered in patients with CF. These findings do not support a global defect in proximal renal tubular reabsorption as the underlying cause for altered aminoglycoside clearance in patients with CF.

Acute Kidney Injury↗

Atenolol and celiprolol for stable angina pectoris.

Once-daily atenolol and celiprolol were compared in a placebo-controlled crossover study of 16 patients with stable angina pectoris. Atenolol and celiprolol equally and significantly reduced frequency of angina and electrocardiographic evidence of cardiac ischemia. Celiprolol, however, produced less suppression of the double product at 1 mm of ST-segment depression than atenolol, suggesting that actions other than reduction of heart rate may contribute to its antianginal efficacy.

Adrenergic beta-Antagonists↗

Dosage regimen of cimetidine reviewed. Possible drug accumulation after multiple oral doses.

The doses of cimetidine recommended differ in children, especially those with cystic fibrosis. These dosage regimens were derived from single-dose pharmacokinetic studies of the drug. Some authors showed, however, that after administration of repeated oral doses of cimetidine in healthy adults and children with cystic fibrosis, the elimination half-life of the drug was markedly prolonged. In view of the ability of cimetidine to inhibit metabolism of other drugs, it is suggested that the parent compound and/or it is metabolite(s) may inhibit its own metabolism during a prolonged course of treatment. Enterohepatic recirculation of the drug and/or its metabolite(s) may also contribute to prolongation of its elimination. One should therefore be cautious in using single-dose pharmacokinetic parameters to calculate repeated dose regimens and expected plasma steady-state concentrations.

Administration, Oral↗

Replication of rat virus in neonatal calvaria in culture.

Rat Virus, a parvovirus of rodents that produces a variety of developmental disturbances of the head and face in neonatal animals, was examined for its ability to replicate in neonatal calvariae in vitro. The bones were isolated and infected with RV within 1 d of birth and cultured for up to 7 d. Virus from the bones and supernatant was titered, and the cellular location of replication determined using in situ hybridization. The virus readily replicated in the isolated bony tissues, reaching titers of nearly 10(7) plaque-forming units/ml. Using viral and complementary strand-specific probes, replication sites were located in the sutures and calvarial bones, as well as in cartilages thought to be part of the neurocranium. Results suggest that the virus localizes and replicates in cells necessary for the normal growth and development of the skull.

Animals↗

Discordance in deoxyribonucleic acid analysis of fetus and trophoblast.

Molecular analysis of deoxyribonucleic acid extracted from trophoblast has become an important component of modern prenatal diagnosis. Discrepancies between trophoblast and fetal tissue in both chromosomal and metabolic analysis have been reported. We studied 50 paired fetal and trophoblast deoxyribonucleic acid specimens with a highly polymorphic probe for repetitive "minisatellite" regions of deoxyribonucleic acid that may be areas of high recombination. Four pairs showed persistent variations in bands consistent with differences in fetal and trophoblast deoxyribonucleic acid. Discordance in trophoblast deoxyribonucleic acid as a reflection of fetal genotype may be secondary to mitotic recombination or sister chromatid exchange in the trophoblast, and the possibility of discordance must be considered in interpreting the results of prenatal diagnostic testing on trophoblast specimens.

DNA↗

Microbial ecology of the terrestrial subsurface.

We have presented a current view of the microbial ecology of the terrestrial subsurface by considering primarily the ecology of shallow aquifer sediments. The properties of the aquifer sediments and groundwater determine their ability to support microbial life and control the abundance and activities of microorganisms. Pore size, nutrient limitations, availability of electron acceptors, and large surface area for attachment all may have major effects on microbial abundance and activities in aquifer material. Microorganisms are the predominant forms of life in the subsurface. They will be found wherever enough space, nutrients, and water are available for them to live. Environmental factors such as pH, temperature, hydrostatic pressure, and dissolved salts also may influence subsurface microbial populations, but these factors do not exhibit great extremes in shallow water table aquifers, and thus only in very deep formations might they limit diversity or preclude the existence of microorganisms. Although the presence and activity of microorganisms in most subsurface environments are predictable, only recently have subsurface microbial populations in shallow subsurface zones been characterized. Aseptic sampling methods have been employed and microbiological and biochemical methods have been adapted to determine the types, abundance, and metabolic activities of microorganisms in subsurface material. Bacteria dominate, but eukaryotic microorganisms also are present. Vertical profile studies of a shallow aquifer in Oklahoma showed that active microbial biomass declined with depth to the unsaturated zone, but was variable in saturated sediments. Such a distribution of active biomass may be common in shallow aquifers. Studies on the lateral distribution of microorganisms in shallow and deep aquifers suggest that microorganisms are transported or migrate over fairly long distances in aquifer sediments. Surficial aquifers may be colonized by vertical or lateral transport and migration of surface microorganisms from recharge areas, but microorganisms could also have colonized when sediments were originally deposited. The biological and physical mechanisms controlling the migration of microorganisms in aquifers are not well understood. The function of shallow aquifers was considered with regard to nutritional ecology. Most pristine aquifers are oligotrophic. Heterotrophic life in these unique ecosystems is supported by secondary organic compounds that filter down from the soil above. The quantity and quality of organic nutrients depend on the age of water and rate of recharge of the aquifer.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

Visual event perception in alcoholics.

A series of microcomputer-based procedures were devised to investigate the ability of alcoholics to detect and locate rapid visual changes, and to assess deficits of visual processing in this patient population. Forty alcoholics were tested 7-13 days after cessation of drinking (mean period of abstinence = 9.5 days), and 24 were retested 2-3 weeks later (mean abstinence = 27.8 days). In comparison to a matched control group the alcoholics were impaired on initial testing at locating visual events. Alcoholics also had significantly slower movement times in a visual-choice reaction time task, and were slower on visual search. At retest the alcoholics were impaired on one of the event perception tasks. Alcoholics were not impaired initially on a measure of visual memory span but were impaired at retest, possibly due to a learning deficit. It is concluded that alcoholics show a persisting deficit in the ability to notice and locate rapid visual changes, together with a transitory impairment on timed tasks requiring visually guided movement.

Adult↗

Angina pectoris during exercise--relationship to coronary anatomy and myocardial function.

We studied 34 patients with proven coronary heart disease to determine whether the presence or absence of angina pectoris during exercise testing was associated with greater disease, ST segment depression or fall in left ventricular ejection fraction. Angina pectoris was the limiting symptom in 19 and fatigue/breathlessness in 15 patients. Exercise time [421(31) vs. 455(64) s], ST depression [1.4(0.3) vs. 1.1(0.3)mm], fall in left ventricular ejection fraction [13(2) vs. 12(2)] and coronary score and fall in left ventricular ejection fraction [15(2) vs. 8(3), P less than 0.02]. The degree of ST segment depression correlated with the coronary score (r = 0.6) and fall in left ventricular ejection fraction (r = 0.5). ST segment depression but not angina pectoris during exercise predicted the extent of disease and its functional consequences.

Angina Pectoris↗

Importance of ancillary properties of beta blockers in angina: a study of celiprolol and atenolol.

Celiprolol (400 mg) and atenolol (100 mg) were given once a day to 16 patients with stable angina pectoris in a double blind placebo controlled crossover study. Celiprolol produced less suppression of heart rate both at rest and during exercise than atenolol. Both drugs were equally effective in reducing the frequency of angina and in delaying the onset of ischaemia during exercise. Radionuclide ventriculography showed that atenolol but not celiprolol lowered cardiac output at rest and during exercise. Thus the ancillary properties of celiprolol, including partial beta 2 agonist activity and direct vasodilating activity, have detectable effects on cardiac function that may be beneficial in patients with angina.

Adrenergic beta-Antagonists↗

Early and late magnetic resonance imaging and neuropsychological outcome after head injury.

Twenty five adults with closed head injury who had early magnetic resonance imaging (MRI) and computed tomography (CT) were followed up 5 to 18 months after injury. Patients were given a repeat MRI and performed a series of neuropsychological tests. They were classified by the deepest abnormality detectable on scanning. Classifications derived from early and late MRI scanning were significantly correlated. However, measures of neuropsychological outcome showed a strong correlation only with late MRI, and little or no relationship with either early MRI or early CT. Deeper abnormalities detected by late MRI were associated with poorer neuropsychological test performance; late ventricular enlargement was particularly associated with poor outcome. It is concluded that the lesions visualised by MRI are important for neuropsychological outcome, and that functionally significant abnormalities may only be fully apparent on late scanning.

Adolescent↗

Celiprolol and atenolol in angina--effects on left ventricular function.

Celiprolol, 400 mg once daily, and atenolol, 100 mg once daily, were compared in a double-blind placebo-controlled crossover study of 16 patients with stable angina. Both drugs reduced angina frequency and delayed the onset of ischaemia during exercise, although only celiprolol prolonged exercise time. Celiprolol produced less suppression of heart rate than atenolol during exercise, and atenolol, but not celiprolol, lowered resting and exercise cardiac output. Thus, the ancillary properties of celiprolol, including partial beta 2-adrenoceptor agonist activity and direct vasodilating activity, have detectable effects on cardiac function that may be beneficial in patients with angina.

Adrenergic beta-Antagonists↗