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Biomedical subjects

R C Wilson

Publications and source records attributed to R C Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1997

A sociodemographic analysis of inpatient oral surgery: 1989-1994.

This retrospective study was designed to assess the socioeconomic status of patients who underwent inpatient oral operations from 1989 to 1994 in the area covered by the West Midlands Regional Health Authority and to compare the distribution with those people treated by other specialties. A total of 4,926,438 hospital inpatient finished consultant episodes within 56 specialties that were recorded on the Hospital Episode Statistics database, of which 61,360 (1.25%) were dental (coded as oral surgery, restorative dentistry, orthodontics, and paediatric dentistry). The main outcome measure was the socioeconomic status of patients as assessed by the Townsend score (a measure of material deprivation that covers car ownership, home ownership, overcrowding, and unemployment). There was a highly significant correlation between the use of all inpatient services and social deprivation (R2 = 0.98, P < 0.001). This observation was consistent across all specialties except oral surgery, in which the correlation was reversed (R2 = 0.69, P < 0.001), indicating that patients who avail themselves of inpatient oral surgery are from a higher socioeconomic group. The application of a deprivation index to hospital episode data will enable purchasers and providers to measure more accurately the impact of their services on groups within the community.

Automobiles↗
PubMed1997

Missouri's statewide outcomes study: lessons and surprises from the public sector.

Demand is increasing for statewide outcomes initiatives and greater focus on studies of treatment effects for publicly funded patients. Such initiatives pose enormous challenges in management--to involve key stakeholders, to protect confidentiality, and to comply with methodological standards. The state of Missouri is taking a leadership role in this direction.

Humans↗
PubMed1996

Point mutations abolish 11 beta-hydroxysteroid dehydrogenase type II activity in three families with the congenital syndrome of apparent mineralocorticoid excess.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts cortisol into mineralocorticoid receptor inactive cortisone, thus preventing occupation of the non-selective mineralocorticoid receptor by glucocorticoids in the kidney. Mutations generating inactive enzymes have been described in the HSD11B2 gene in the congenital syndrome of apparent mineralocorticoid excess (AME), although proof of mutant protein synthesis was not provided. In the present study we have examined the metabolism of cortisol in mammalian cells transfected with plasmids expressing the wild type and mutant enzymes from three additional families of patients with mutations in the HSD11B2 gene. These studies revealed that the mutants were enzymatically inactive in intact mammalian cells expressing significant levels of both full length and truncated proteins. This is the first study to definitively show that point mutations in the HSD11B2 gene abolish 11 beta HSD2 enzymatic activity in the syndrome of AME.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Detection of a sub-set of polysomal mRNAs associated with modulation of hypusine formation at the G1-S boundary. Proposal of a role for eIF-5A in onset of DNA replication.

S phase entry, i.e. start of DNA replication, is a crucial step in proliferation. Inhibition of S phase entry correlates with inhibition of hypusine formation, an event affecting only the eukaryotic initiation factor 5A (eIF-5A). Its hypusine-containing sequence was postulated to authorize polysomal utilization of specific transcripts for proteins necessary to enable DNA replication. Using mimosine to reversibly suppress the hypusine-forming deoxyhypusyl hydroxylase (E.C. 1.14.99.29) in cells while differentially displaying their polysomal versus non-polysomal mRNA populations, we report the detection and classification of several mRNA species that indeed disappear from and reappear at polysomes in concert with inhibition and disinhibition, respectively, of hypusine formation. Based on initial sequence data, two translationally controlled enzymes, both critical for proliferation, are identified as candicate products of such mRNAs, methionine adenosyltransferase (E.C. 2.5.1.6) and cytochrome-c oxidase (EC 1.9.3.1) subunit I. The existence of such putative hypusine-dependent messenger nucleic acids (hymns) provides the basis for a proposal on their molecular function in onset of multiplication.

Base Sequence↗
PubMed1995

Pharmacokinetics of ciprofloxacin in ponies.

The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two-compartment open model with first-order elimination from the central compartment. Mean plasma half-life, based on the terminal phase, was 157.89 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 +/- 3.99 mL/min/kg. Volume of distribution at steady-state was 3.45 +/- 0.72 L/kg. From the pharmacokinetic data and reported minimum inhibitory concentrations for equine gram-negative pathogens, the appropriate dosage of ciprofloxacin was determined to be 5.32 mg per kg body weight at 12 h intervals. Bioavailability of oral ciprofloxacin in ponies was 6.8 +/- 5.33%. Owing to the poor bioavailability, a dosage regimen could not be proposed for oral ciprofloxacin administration in horses. Ciprofloxacin concentrations were determined in tissues and body fluids at 1, 2 and 4 h after intravenous administration. At all times, tissue concentrations exceeded plasma concentrations of ciprofloxacin. Highest concentrations were achieved in kidneys and urine. Potentially therapeutic concentrations were obtained in cerebrospinal and joint fluid, but low concentrations were achieved in aqueous humour.

Administration, Oral↗
PubMed1995

Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess.

Four deleterious mutations are described in the gene for HSD11B2, which encodes the type 2 isoenzyme of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD2). In seven families with one or more members affected by apparent mineralocorticoid excess, this disorder is shown to be the result of a deficiency in 11 beta HSD2. Surprisingly, the patients are all homozygous for their mutation. This results from consanguinity in two families and possibly from endogamy or a founder effect in four of the other five families. The absence of compound heterozygotes remains to be investigated.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

The R337C mutation generates a high Km 11 beta-hydroxysteroid dehydrogenase type II enzyme in a family with apparent mineralocorticoid excess.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) inactivates glucocorticoids in the kidney and thus permits aldosterone to occupy the non-selective mineralocorticoid receptor in epithelial tissues. We have recently described a C to T transition in the HSD11B2 gene which results in an arginine to cysteine mutation (R337C) in the 11 beta HSD2 enzyme in a consanguineous family with three siblings suffering from Apparent Mineralocorticoid Excess (AME). In the present study we have examined the metabolism of cortisol in mammalian cells transfected with plasmids expressing the wild type and mutant enzymes. In whole cells the Km of the normal enzyme was 110nM, while the enzyme containing the R337C mutation displayed a Km of 1010nM. Further experiments revealed that the mutant was totally inactive in cell free preparations, suggesting that it has additional properties which may compromise its activity in whole cells.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Rapid deoxyribonucleic acid analysis by allele-specific polymerase chain reaction for detection of mutations in the steroid 21-hydroxylase gene.

Rapid DNA analysis based on allele-specific polymerase chain reaction (PCR) using mutation site-specific primers was developed to detect mutations in the CYP21 gene known to cause steroid 21-hydroxylase deficiency. In contrast to the previous method, in which PCR of genomic DNA was followed by dot blot analysis with radioactive probes and multiple rounds of stripping and reprobing for each of the 8 most common mutation sites, the results using this new method were immediately visualized after the PCR run by ethidium bromide-stained agarose gel electrophoresis. Using allele-specific PCR, mutation(s) were identified on 148 affected chromosomes out of 160 tested. Although mutation(s) were identified on only one chromosome of 11 of these patients, their parents showed a consistent pattern on DNA analysis. The only exception was that in one family, in which the parents each had a detectable mutation, a mutation was detected on only one allele of the patient. Most likely there is a mutation in the patient's other allele that could have arisen de novo or was inherited from the parent and was not evident in the transmitting parent's phenotype. When compared with the dot blot procedure, allele-specific PCR is more rapid, less labor-intensive, and avoids the use of radioactivity.

Alleles↗
PubMed1995

Prenatal treatment and diagnosis of congenital adrenal hyperplasia owing to steroid 21-hydroxylase deficiency.

Since 1986, prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) have been carried out in 239 pregnancies. In 145, diagnoses were made by amniocentesis, whereas 77 were diagnosed using chorionic villus sampling. A newly developed, rapid allele-specific polymerase chain reaction was used for DNA analysis in some cases. Of 239 pregnancies evaluated, 37 babies were affected with classical 21-OHD. Of these, 21 were females, 13 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 10 weeks gestation (9 affected female fetuses) was effective in reducing virilization. Seven fetuses had affected female siblings (Prader stages 1-5); 3 of these were born with entirely normal female genitalia, whereas the other 4 were significantly less virilized (Prader stages 1-2) than their siblings. The remaining 2 newborns had male siblings; 1 was born with normal genitalia, and the other was Prader stage 1. No significant or enduring side-effects were noted in either the mothers or the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight, length, or head circumference from untreated unaffected newborns. Based on our experience, proper prenatal diagnosis and treatment of 21-OHD is effective in significantly reducing or eliminating virilization in the affected female. This spares the newborn female the consequences of genital ambiguity, i.e. genital surgery, sex misassignment, and gender confusion.

Adrenal Hyperplasia, Congenital↗
PubMed1995

Steroid 21-hydroxylase deficiency: genotype may not predict phenotype.

Steroid 21-hydroxylase deficiency is the most frequent cause of congenital adrenal hyperplasia. We have determined the 21-hydroxylase genotype in 197 patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency and assessed phenotypic characteristics based on 1) genital status with respect to virilization in females, 2) ACTH stimulation tests to evaluate the secretion of androgens and 17-hydroxyprogesterone, and 3) salt deprivation tests to precisely describe the phenotype with respect to aldosterone deficiency and salt wasting. After dividing our patients into 26 21-hydroxylase gene mutation-identical groups, we found that, in general, the patient's phenotype matched the severity of the genotype. However, in 13 of these groups, the genotype did not always predict the phenotype, even within families. This study, has demonstrated that the 10 most common mutations observed in the 21-hydroxylase gene result in phenotypes that are not always concordant with the genotype.

Adrenal Hyperplasia, Congenital↗
PubMed1995

Ceftiofur distribution in serum and milk from clinically normal cows and cows with experimental Escherichia coli-induced mastitis.

Eight Holstein cows, 4 inoculated intracisternally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean +/- SEM peak log10 bacterial concentration in milk of 5.03 +/- 0.69 colony-forming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 +/- 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 +/- 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 +/- 27.5 hours) than noninfected cows (1.3 +/- 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 microgram/ml, and was 0.20 microgram/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 +/- 0.3 microgram/ml and 0.7 +/- 0.1 microgram/ml for infected and noninfected cows, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Caffeine clearance in the horse.

The pharmacokinetic properties of intravenously administered caffeine were studied in 10 horses using a commercially available automated enzyme immunoassay. The harmonic mean for the distribution half-life was 5.2 min (range 1.4-18.7). The harmonic mean for the elimination half-life was 10.18 h (range 6.82-20.92). The harmonic mean of the volume of distribution was 0.32 L/kg (range 0.22-0.53). There was no correlation between the dose of caffeine/kg body weight and the elimination half-life (Spearman's coefficient of rank correlation = 0.19).

Animals↗
PubMed1994

A new proline-rich early nodulin from Medicago truncatula is highly expressed in nodule meristematic cells.

We cloned and characterized MtPRP4, a new member of the repetitive proline-rich protein gene family in Medicago truncatula. The sequence of MtPRP4 predicts a 62-kD protein consisting of a 22-amino acid N-terminal signal peptide and a 527-amino acid repetitive proline-rich domain composed of three repetitive pentapeptide motifs arranged into two decapeptide repeats: PPVEKPPVHK and PPVEKPPVYK. MtPRP4 is the largest PRP described to date and contains repeated motifs that have not previously been found together in a single polypeptide. RNA gel blot experiments detected MtPRP4 transcripts in symbiotic root nodules, but not in roots, hypocotyls, or leaves. Accumulation of MtPRP4 transcript was an early response to Rhizobium inoculation and did not depend on nodule infection. In situ hybridization experiments demonstrated that MtPRP4 was expressed early in the development of the nodule meristem and that expression was highest in the meristematic cells of mature indeterminate nodules. These data support the proposition that an important early response of legume host roots to Rhizobium involves remodeling the host extracellular matrix and that proline-rich wall proteins play an important role in this architectural modification.

Amino Acid Sequence↗