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Biomedical subjects

R C Wilson

Publications and source records attributed to R C Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Variations in admission to hospital for head injury and assault to the head. Part 2: Ethnic group.

This study retrospectively investigated variations in the use of secondary healthcare for head injury, particularly assault. A total of 25,300 emergency head-related admissions were examined over a two-year period, of which 3756 were assaults. There were seasonal differences according to ethnic group: far more injuries, particularly assault, occurred amongst the black and minority ethnic groups during the summer months and holidays. Black males had two to three times the rate of admission for assault than any other group. Among whites, females stayed longer in hospital after a head injury. White women stayed significantly longer than South Asian women following a head injury and South Asian men stayed significantly longer than white men after an assault. There are substantial seasonal variations and differences in the length of hospital stay after a head injury, particularly assault, depending on ethnic group. These differences require clarification and more detailed studies of head injuries ought to record the patient's ethnic background.

Black or African American↗
PubMed1999

Glucocorticoid resistance caused by reduced expression of the glucocorticoid receptor in cells from human vascular lesions.

Mechanisms that control the balance between cell proliferation and death are important in the development of vascular lesions. Rat primary smooth muscle cells were 80% inhibited by low microgram doses of hydrocortisone (HC) and 50% inhibited by nanogram concentrations of transforming growth factor-beta1 (TGF-beta1), although some lines acquired resistance in late passage. However, comparable doses of HC, or TGF-beta1, failed to inhibit most human lesion-derived cell (LDC) lines. In sensitive LDC, HC (10 microg/mL) inhibited proliferation by up to 50%, with obvious apoptosis in some lines, and TGF-beta1 inhibited proliferation by more than 90%. Collagen production, as measured by [3H]proline incorporation or RIA for type III pro-collagen, was either unaffected or increased in the LDCs by HC. These divergent responses between LDC lines were partially explained by the absence of the glucocorticoid receptor (GR) and heat shock protein 90 mRNA in 10 of 12 LDC lines, but the presence of the mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II. Western blot analysis confirmed the absence of the GR protein in cells lacking GR mRNA. Immunohistochemistry of human carotid lesions showed high levels of GR in the tunica media, but large areas lacking GR in the fibrous lesion. Considering the absence of the GR in most lines, the effects of HC may be elicited through the mineralocorticoid receptor. Functional resistance to the antiproliferative and antifibrotic effects of HC may contribute to excessive wound repair in atherosclerosis and restenosis.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Intrauterine growth retardation associated with maternal uniparental disomy for chromosome 6 unmasked by congenital adrenal hyperplasia.

We report the first case of maternal uniparental disomy for chromosome 6 (UPD6mat) ascertained through congenital adrenal hyperplasia (CAH), which arose because of reduction to homozygosity of an autosomal recessive mutation. This case suggests that UPD6mat is associated with intrauterine growth retardation (IUGR). A case of paternal UPD (involving only the short arm of chromosome 6) ascertained as CAH has previously been reported, but was not stated to have IUGR. Our patient was born with IUGR followed by extraordinarily good catch-up growth. She had a history of a marked lag in motor development. She presented at 2.65 y of age with pubarche of 3 mo duration, clitoral enlargement, and an advanced bone age. Simple virilizing CAH was diagnosed by elevations of plasma 17-hydroxyprogesterone and testosterone. Mutation analysis showed that the CAH was due to homozygosity for the 1172N exon 4 mutation. When parental DNA was examined, the mother was found to be heterozygous for the uncommon exon 4 mutation, while the father had no detectable mutations. DNA microsatellite analysis was subsequently performed on the patient and parents using polymorphic markers spanning the entire chromosome 6. Seven markers were informative for inheritance of a single maternal allele and absence of paternal alleles in the proband. Analysis of microsatellite markers from other chromosomes confirmed biparental inheritance at these loci. This combination of findings is diagnostic of UPD6mat. The only other reported case of UPD6mat was discovered serendipitously when genotyped for renal transplantation; this patient had a history of IUGR. Since both cases of UPD6mat had IUGR, the phenotype appears to include IUGR as well as the potential to unmask an autosomal recessive trait.

Adrenal Hyperplasia, Congenital↗
PubMed1999

Congenital adrenal hyperplasia (21-hydroxylase deficiency) without demonstrable genetic mutations.

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is the most common inherited defect of adrenal steroid biosynthesis. At least 36 mutations in the CYP21 gene, which is mapped to chromosome 6p21.3, have been described. We performed genetic analysis of the CYP21 gene in a patient with classic 21-OHD CAH and her family. The entire exonic coding regions and intronic regions, as well as the -1 kb 5' upstream promoter region, were thoroughly sequenced and analyzed. Despite extensive sequencing, no mutation was found in this 3.7 kb area. The 11beta-hydroxylase defect, closely mimicking the clinical and biochemical phenotype of classic 21-OHD, was excluded by directly sequencing 2.6 kb covering the entire coding of the CYP11B1 gene. Herein we describe a phenotypically and hormonally affected patient with classic simple virilizing 21-OHD CAH who lacks a mutation in the entire CYP21 gene and coding region of the CYP11B1 gene.

Adrenal Hyperplasia, Congenital↗
PubMed1999

Resistance to several steroids in two sisters.

A 14-yr-old native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of apparent mineralocorticoid excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens, but no resistance to vitamin D or thyroid hormones. She lacked Cushingoid features despite significantly high cortisol levels. Menstruation was regular, and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly due to a coactivator defect.

Adolescent↗
PubMed1999

Prevalence of mild apparent mineralocorticoid excess in Mennonites.

UNLABELLED: We have studied an unusual patient with mild low-renin hypertension due to a homozygous mutation in the HSD11B2 gene (PNAS 95:10200-10205, 1998). The patient came from an inbred Mennonite family, and though the mutation identified her as an AME patient, she had a normal birth weight and did not demonstrate the typical features of AME, such as hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. Biochemically, typical patients with AME have abnormal cortisol metabolites and an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. In this patient with mild AME, the conversion of cortisol to cortisone was 58% compared to 0 to 6% in typical AME patients, while the normal conversion is 90 to 95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous mutation in codon 227 (P227L). We studied this Mennonite population for the prevalence of the P227L mutation. Our hypothesis was that this mild form of AME would be prevalent in the somewhat inbred Mennonite population to which the patient belongs. Our proposed study was 1) to determine if there are other cases of this mild form of AME, and 2) to establish the heterozygote frequency of the mutation in the Mennonites. RESULTS: We did not detect any additional cases of mild AME. We detected 15 carriers of the P227L mutation out of 445 Mennonites, resulting in a heterozygote frequency of 0.03. CONCLUSION: Since this is an inbred population, the chance of two heterozygotes marrying would be 0.001, which is 1 in 1000 people. This population is known to have large families and therefore the possibility of having an affected child is high. The population consists of 2000 members and we have discovered one affected patient. Thus, there might be one other patient in this population.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Prenatal diagnosis and treatment of 11beta-hydroxylase deficiency congenital adrenal hyperplasia resulting in normal female genitalia.

Congenital adrenal hyperplasia (CAH) consists of autosomal recessive disorders of cortisol biosynthesis, which in the majority of cases result from 21-hydroxylase deficiency. Another enzymatic defect causing CAH is 11beta-hydroxylase deficiency. In both forms, the resulting excessive androgen secretion causes genital virilization of the female fetus. For over 10 yr female fetuses affected with 21-hydroxylase deficiency have been safely and successfully prenatally treated with dexamethasone. We report here the first successful prenatal treatment with dexamethasone of an affected female with 11beta-hydroxylase deficiency CAH. The family had two girls affected with 1beta-hydroxylase deficiency born with severe ambiguous genitalia who were both homozygous for the T318M mutation in the CYP11B1 gene, which codes for the 11beta-hydroxylase enzyme. In the third pregnancy in this family, the female fetus was treated in utero by administering dexamethasone to the mother, starting at 5 weeks gestation. The treatment was successful, as the newborn was not virilized and had normal female external genitalia. A second family with two affected sons was also studied in preparation for a future pregnancy. We report a novel 1-bp deletion in codon 394 (R394delta1) in the CYP11B1 gene in this family.

Adrenal Hyperplasia, Congenital↗
PubMed1999

The use of low-dose trazodone in the treatment of painful diabetic neuropathy.

Thirty-one adult diabetic patients with painful distal symmetrical polyneuropathy were treated with low doses of oral trazodone (50 or 100 mg/day). After 2 weeks of therapy, 19 patients (61.3%) experienced symptomatic relief, and 7 (22.6%) experienced complete relief. Although 8 patients (25.8%) discontinued the drug because of side effects, these were relatively minor (dizziness, headache, insomnia). Low-dose trazodone is recommended as an effective treatment option for painful diabetic neuropathy.

Adult↗
PubMed1998

A genetic defect resulting in mild low-renin hypertension.

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) cause AME. Typical patients with AME have defective 11beta-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the HSD11B2 gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0-6% in typical patients with AME whereas the normal conversion is 90-95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C-->T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation. In vitro expression studies showed an increase in the Km (300 nM) over normal (54 nM). Because approximately 40% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the HSD11B2 gene.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Variations in hospitalization rates for asthma among black and minority ethnic communities.

In response to the introduction of ethnic monitoring within the U.K. hospital inpatient data set, this study investigates the variations in secondary healthcare utilization by Black and minority ethnic communities whose cause of admission is related to asthma. The study examines all residents of the West Midlands: over 5 million people, of whom 8.5% are from Black and minority ethnic groups. A retrospective study of 15,921 asthma-related hospital admissions, from 1 April 1995 to 31 March 1996, was carried out. Age-standardized admission rates were higher in all Black and minority ethnic groups studied than in the White group. There were elevated rates in Black children aged 5-14 years, and particular differences were observed for Indian and Bangladeshi men and women aged 65 years or over. Emergency admissions to hospital for asthma were strongly associated with patients' socioeconomic background but this was largely observed for Black and minority ethnic groups that also generally experience high levels of deprivation. The findings support previous studies which suggest that hospital utilization rates for asthma among people from Black and minority ethnic groups are high compared with the White group, despite little evidence in measured prevalence. This study suggests that ethnic background is more important in asthma admissions than deprivation, which raises serious concerns on the appropriateness and quality of asthma care for these patient groups within our society. Future studies need to examine pathways to care, that is the health-seeking behaviour of Black and minority ethnic groups, the type of treatment received at the primary care level and referral patterns to secondary care.

Adolescent↗
PubMed1998

Anaesthesia for caesarean section in a patient with Charcot-Marie-Tooth disease.

We describe the management of a 25-year-old primigravida with severe respiratory insufficiency secondary to CHarcot-Marie-Tooth disease type I scheduled for Caesarean section. Incremental subarachnoid anaesthesia via a microcatheter was utilised. Mother and baby made an uneventful recovery and were discharged home on the tenth postoperative day.

Adult↗
PubMed1998

Epidural pain relief in labour: potencies of levobupivacaine and racemic bupivacaine.

We have compared the minimum local analgesic concentrations (MLAC) of levobupivacaine relative to racemic bupivacaine in a prospective, randomized, double-blind, sequential allocation study. Women in labour were given a 20-ml bolus of epidural levobupivacaine or bupivacaine diluted to a concentration determined by up-down sequential allocation. The initial concentration was 0.07% w/v for both drugs. Efficacy was defined using a visual analogue pain score (VAPS) at 10 mm or less within 30 min. The MLAC of levobupivacaine was 0.083% w/v (95% CI 0.065-0.101) and the MLAC of bupivacaine 0.081% w/v (95% CI 0.055-0.108). In molar terms, the MLAC of levobupivacaine was 2.87 mmol litre-1 (95% CI 2.25-3.49) and the MLAC of bupivacaine 2.49 mmol litre-1 (95% CI 1.69-3.32). With regard to the commercial preparations, the potency ratio levobupivacaine: bupivacaine was 0.98 (95% CI 0.67-1.41), and this is unlikely to be of clinical relevance. In molar terms, the ratio was 0.87 (95% CI 0.60-1.25). With regard to toxicity, the evidence should be evaluated in the light of a possible 13% potency difference in molar concentration in favour of racemic bupivacaine.

Adult↗
PubMed1998

An epidemiological study of acute carbon monoxide poisoning in the West Midlands.

OBJECTIVES: To describe the epidemiology of carbon monoxide (CO) poisoning in a defined population, identifying those at greatest risk from acute poisoning resulting in admission to hospital or death. METHODS: A retrospective study with routinely collected information, set in the former West Midlands Regional Health Authority; population of 5.2 million. The data comprised 939 deaths and 701 hospital admissions due to CO poisoning between January 1988 to December 1994. The main outcome measures were age and sex standardised incidence rates (SIRs) for non-intentional, suicidal, and undetermined poisonings for health authorities and the linear relation with socioeconomic deprivation. RESULTS: Overall rate of non-intentional poisonings over the 7 year period was 7.6/100,000, an annual rate of 1.1/100,000. The 7 year rates were highest in people > or = 85; men 24.0/100,000 and women 19.7/100,000. For suicides the 7 year rate was 19.6/100,000, an annual rate of 2.8/100,000. The 7 year rates were highest for men of 35-39, 64.1/100,000, and for women aged 45-49, 15.3/100,000. None of the causes of poisoning were related to deprivation. Non-intentional poisonings showed a strong seasonal variation with the highest rates being recorded in the months October to March. Increased rates of poisoning were found in the rural districts of the West Midlands. There seems to have been a decline in suicides coinciding with the introduction of three way catalytic converters on cars. CONCLUSIONS: Elderly people and the very young are at the greatest risk from non-intentional CO poisoning and rates are highest in the winter months. Although deaths from non-intentional CO poisoning are declining nationally, in the West Midlands they have remained stable and hospital admissions are increasing. It is not solely an urban phenomenon with rates for non-intentional CO poisoning and suicides higher in the rural districts. Health authorities need to consider all populations in any prevention programme. Further work is needed to establish the extent of the burden of chronic CO poisoning and the impact of catalytic converters on suicides.

Adolescent↗
PubMed1998

Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) is a genetic disorder causing pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, and hyporeninemic hypoaldosteronism due to a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 enzyme activity (11 beta HSD2). The 11 beta HSD2 enzyme is responsible for the conversion of cortisol to the inactive metabolite cortisone and therefore protects the mineralocorticoid receptors from cortisol intoxication. Several homozygous mutations are associated with this potentially fatal disease. We have examined the phenotype, biochemical features, and genotype of 14 patients with AME. All of the patients had characteristic signs of a severe 11 beta HSD2 defect. Birth weights were significantly lower than those of their unaffected sibs. The patients were short, underweight, and hypertensive for age. Variable damage of one or more organs (kidneys, retina, heart, and central nervous system) was found in all of the patients except one. The follow-up studies of end-organ damage after 2-13 yr of treatment in six patients demonstrated significant improvement in all patients. The urinary metabolites of cortisol demonstrated an abnormal ratio with predominance of cortisol metabolites, i.e. tetrahydrocortisol plus 5 alpha-tetrahydrocortisol/tetrahydrocortisone was 6.7-33, whereas the normal ratio is 1.0. Infusion of [11-3H]cortisol resulted in little release of tritiated water, indicating the failure of the conversion of cortisol to cortisone. Thirteen mutations in the HSD11B2 gene have been previously published, and we report three new genetic mutations in two patients, one of whom was previously unreported. All of the patients had homozygous defects except one, who was a compound heterozygote. Our first case had one of the most severe mutations, resulting in the truncation of the enzyme 11 beta HSD2, and died at the age of 16 yr while receiving treatment. Three patients with identical homozygous mutations from different families had varying degrees of severity of clinical and biochemical features. Due to the small number of patients with identical mutations, it is difficult to correlate genotype with phenotype. In some cases, early and vigilant treatment of AME patients may prevent or improve the morbidity and mortality of end-organ damage such as renal or cardiovascular damage and retinopathy. The outcome of treatment in more patients may establish the efficacy of treatment.

Adolescent↗
PubMed1998

Effects of Yucca shidigera extract and soluble protein on performance of cows and concentrations of urea nitrogen in plasma and milk.

Twelve multiparous Holstein cows averaging 122 d postpartum were used in a replicated Latin square design with 21-d periods. Cows were fed diets containing either low or high soluble protein supplemented with 0 or 9 g/d of Yucca shidigera extract per cow. Dry matter intake and yields of milk, fat, 3.5% fat-corrected milk, and total solids were not affected by treatment. High soluble protein increased percentages of fat and total solids in milk but decreased percentages of crude protein and true protein in milk. Yucca shidigera extract did not affect percentages or yields of milk components, ruminal NH3 N, or urea N in milk or plasma. High soluble protein tended to increase both ruminal pH and concentrations of ruminal NH3 N. Yucca shidigera extract did not affect ruminal pH or NH3 N. High soluble protein increased concentrations of urea N in plasma and milk when both were measured by enzymatic assay, but differences in milk urea N measured by mid infrared reflectance spectroscopy were not significant. Neither Yucca shidigera extract nor increased ruminally undegradable protein was beneficial in this trial when fed to cows milking 30 to 35 kg/d. Concentrations of urea N in milk as measured by mid infrared reflectance spectroscopy were higher than those measured by enzymatic assay, but measurements by mid infrared reflectance spectroscopy were not as sensitive to treatment differences as were measurements by enzymatic assay.

Ammonia↗
PubMed1998

Steam pasteurization of commercially slaughtered beef carcasses: evaluation of bacterial populations at five anatomical locations.

A steam pasteurization process (patent pending) has been shown to effectively reduce pathogenic bacterial populations on beef tissue and to significantly reduce naturally occurring bacterial populations on commercially slaughtered beef carcasses. The objective of this study was to determine the effectiveness of the steam pasteurization treatment for reducing bacterial populations at several anatomical locations on commerically slaughtered carcasses. Before and after pasteurization treatment (82.2 degrees C, 6.5-s exposure time), a sterile sponge was used to sample 300 cm2 at one of five locations (inside round, loin, midline, brisket, or neck). Eighty carcasses (40 before treatment and 40 after treatment) were sampled per anatomical location over 2 processing days. Before treatment, aerobic plate counts (APCs) were found to be highest (P < or = 0.01) at the midline (4.5 log10 CFU/100 cm2), intermediate at the inside round, brisket, and neck (ca. 3.8 log10 CFU/100 cm2), and lowest at the loin (3.4 log10 CFU/100 cm2). After treatment, APCs at all locations were reduced significantly (P < or = 0.01). The inside round, loin, and brisket had the lowest (P < or = 0.01) APCs (ca. 2.6 log10 CFU/100 cm2), whereas the midline and neck had APCs of 3.1 and 3.3 log10 CFU/100 cm2, respectively. The lower reduction in APCs at the neck area indicated that the treatment may not be as effective there, possibly because of the design of the pasteurization equipment. Generic Escherichia coli populations were low at all locations before treatment, with populations on 32% of all carcasses sampled being less than the detection limit of the study (5.0 CFU/100 cm2). After treatment, E. coli populations were significantly lower (P < or = 0.01) than populations before treatment and 85% of all carcasses sampled had E. coli populations below the detection limit. The maximum E. coli population detected after treatment was 25 CFU/100 cm2. For enteric bacterial populations, no differences were observed in the effectiveness of the treatment among the five carcass locations.

Abattoirs↗
PubMed1997

Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) in Croatia.

We report on the prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase in 20 at-risk pregnancies (16 salt-wasting and 4 simple virilizing families). We have diagnosed 3 affected fetuses (2 males and 1 female), 3 healthy homozygotes (2 males and 1 female), and 14 healthy heterozygotes (7 females and 7 males). These data were collected over 4 years. In 16 fetuses, the diagnosis was made with measurements of 17-hydroxyprogesterone (17-OHP) and delta-4-androstenedione (delta) in amniotic fluid (AF), human leukocyte antigen (HLA) typing of amniotic cells, as well as karyotypes between the 16th and 18th weeks of gestation. In 4 fetuses, DNA analysis of amniotic cells was also performed. In 3 pregnancies in which affected fetuses were suspected (on the basis of HLA typing and measurements of 17-OHP and delta concentrations in AF), the fetuses were electively aborted between the 17th to 19th weeks of gestation by parental decision. In all aborted fetuses, diagnosis was confirmed with HLA typing, autopsy findings of hyperplastic adrenal glands, and ambiguous genitalia in female fetuses. Postnatal diagnosis was confirmed in healthy fetuses with HLA typing and serum measurements of 17-OHP concentrations, and in 4 of them with DNA analysis. In 3 of the 4 families, DNA analyses revealed the following mutations: in Family 1, the index case mutation was Intron 2, Exon 3/Exon 6, and the fetus was Normal/Exon 6; in Family 2, the index case mutation was Ex1 Int2 Ex3/ Int2, and the fetus was Ex1 Int2 Ex3/Normal; and in Family 3, the index case mutation was Ex8(356)/Ex8(356), and the fetus was Ex8(356)/ Normal. We also report one case of prenatal diagnosis and treatment. Dexamethasone 0.5 mg BID (20 micrograms/kg/d) was given starting at 6th week of gestation. Prenatal diagnosis suggested, but did not prove, that the female fetus was a heterozygote as the fetus lacked the paternal mutation Ex8(318). No mutation was found in the mother. The fetus, the mother, and the affected sib shared a haplotype, further suggesting heterozygosity. The unaffected status was confirmed postnatally.

17-alpha-Hydroxyprogesterone↗