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Biomedical subjects

R C Wilson

Publications and source records attributed to R C Wilson.

At least 19 recordsLinked to original sources

Effect of maternal facial oxygen on neonatal behavioural scores during elective Caesarean section with spinal anaesthesia.

BACKGROUND AND OBJECTIVE: For many, the administration of additional oxygen to the women receiving regional anaesthesia for Caesarean section is traditional, but for others it is controversial because of doubts about its efficacy. The aim of our study was to determine if beneficial effects of maternal oxygen therapy on the fetus could be revealed using a neonatal behavioural scoring system. METHODS: Sixty women with a normal singleton pregnancy beyond 36 weeks gestation, undergoing elective Caesarean section under spinal anaesthesia were randomized into two groups: Group 1 received air and oxygen mixture through a Hudson style face mask (FiO2 of 0.21-0.25). Group 2 received FiO2 of 0.40-0.60 through an identical Hudson style face mask. Neurologic Adaptive Capacity Score on all the infants within 5 min of birth and between 10 and 24 h after the Caesarean delivery was performed. Apgar score, umbilical venous blood oxygen tension and umbilical artery standardized base excess were recorded. RESULTS: Initial Neurologic Adaptive Capacity Scores at birth in Groups 1 and 2 were 32.6 (SD 4.6) and 31.3 (SD 4.3), respectively. Latter scores were 36.0 (SD 3.0) and 36.5 (SD 1.9), respectively. Neither were statistically significant. There were no significant differences between the groups for any of the recorded variables. CONCLUSIONS: Administering maternal oxygen using a standard commercial Hudson style face mask does not appear to significantly improve oxygen delivery to, nor does it influence acidosis or behavioural effects in, the normal neonate at elective Caesarean delivery with spinal anaesthesia.

Adult↗

Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section.

BACKGROUND: Comparative studies of ephedrine and phenylephrine in prevention of hypotension after spinal anaesthesia for Caesarean section have lacked a consensus on dose equivalence. The aim of this study was to determine the minimum vasopressor dose for each of these drugs to calculate the dose ratio for clinical equivalence in the prevention of hypotension. METHODS: Patients with a normal singleton pregnancy beyond 36 weeks gestation undergoing elective Caesarean section under spinal anaesthesia were randomized into two groups. The first patient in Group A received 50 mg of ephedrine in saline 0.9% w/v, 500 ml, at 999 ml h(-1), the maximum rate possible on the pump and the first patient in Group B received 500 microg of phenylephrine in saline 0.9% w/v, 500 ml, at the same rate. The initial dose for dilution was an arbitrary choice. The dose of vasopressor in the saline bag for every subsequent patient was established by the efficacy of the dose in preventing hypotension in the previous patient according to the technique of up-down sequential allocation. Minimum vasopressor dose for each drug was determined according to the Dixon-Massey formula. RESULTS: The minimum vasopressor dose in saline 500 ml was 532.9 microg (95% CI 506.0-559.8) for phenylephrine and 43.3 mg (95% CI 39.2-47.3) for ephedrine. The concentration needed for equivalence at an infusion rate of 999 ml h(-1) was 1.07 microg ml(-1) for phenylephrine and 86.66 microg ml(-1) for ephedrine. Mean (sd) dose used for phenylephrine was 496.45 (78.3) microg and for ephedrine 39.64 (6.33) mg. CONCLUSION: This study demonstrates a potency ratio of 81.2 (95% CI 73.0-89.7) for equivalence between phenylephrine and ephedrine in prevention of hypotension after spinal anaesthesia for Caesarean section.

Adolescent↗

Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake from seawater.

Uptake and depuration experiments for the edible periwinkle Littorina littorea have been performed using 131I-labelled seawater. Throughout the experimental phase the winkles were fed on unlabelled Chondrus crispus. 131I concentrations in winkles during uptake followed linear first-order kinetics with an uptake half-time of 11 days, whereas for depuration a triphasic sequence with biological half-lives of 4, 23 and 56 days was determined. In general, iodine turnover in winkles via labelled seawater appears to be slower than observed for other molluscs (2-3 days). Most of the activity prior to and after depuration is found to be in the shell, with indications that shell and soft parts accumulate and depurate 131I at a similar rate. The operculum displays the highest specific activity of all fractions with a concentration factor of 750 l kg(-1). Concentration factors for whole winkle, shell, soft parts and digestive gland are in the order of 40-60 l kg(-1), higher than the IAEA recommended CF value for iodine in molluscs of 10 l kg(-1). The 131I CF in winkles is closer to that of the conservative radionuclides 99Tc and 137Cs than the CF of the particle reactive radionuclides (239,240)Pu and 241Am.

Animals↗

Update on the prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

11beta-Hydroxylase deficiency is a common form of congenital adrenal hyperplasia causing virilization of the female fetus and hypertension. DNA analysis of the gene (CYP11B1) encoding 11beta-hydroxylase has been reported previously to be effective in the prenatal diagnosis of one affected female fetus. In that case, prenatal treatment with dexamethasone resulted in normal female genitalia. We now report five new pregnancies that underwent prenatal diagnosis for 11beta-hydroxylase deficiency. In the first family, the proband is homozygous for a T318M mutation and all fetuses from four subsequent pregnancies are carriers. In a second family, the mother is homozygous for a A331V mutation and was started on dexamethasone, but identification of a homozygous normal fetus led to the discontinuation of treatment. In another family, the fetus was a male homozygous for R384Q and treatment was discontinued. Lastly, a novel G444D mutation in exon 8 was identified and proven to reduce 11beta-hydroxylase activity.

Adolescent↗

The natural history and genotype-phenotype nonconcordance of HLA identical siblings with the same mutations of the 21-hydroxylase gene.

The correlation of genotype to phenotype in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency has been investigated thoroughly since the mapping of the CYP21 gene to the short arm of chromosome 6. In most instances, it is possible to accurately predict the phenotype based on genoytpe; however, in a small number of patients, individuals with identical mutations demonstrate variable phenotypes. We report two HLA-identical brothers who represent a striking case of genotype-phenotype nonconcordance in CAH. Molecular genetic analysis showed both patients had mutations in intron 2 and exon 10 of CYP21. Both brothers underwent salt-deprivation tests at similar ages over three separate hospital admissions. Patient 1 was diagnosed with simple virilizing CAH and was able to maintain sodium balance during salt deprivation tests. Patient 2, 3 years younger, was diagnosed with salt-wasting CAH and was unable to maintain sodium balance but progressively increased his aldosterone secretion with age.

Adolescent↗

Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake from labelled seaweed (Chondrus crispus).

Uptake and depuration experiments of (131)I from labelled seaweed (Chondrus crispus) by the edible periwinkle Littorina littorea have been performed. Radioiodine concentrations in winkles during uptake followed first-order kinetics with an uptake half-time of 1 day, and a calculated equilibrium concentration (C(infinity)) of 21 000 Bq kg(-1) resulting in a transfer factor of 0.07 with respect to the labelled seaweed used as food. For depuration, a biphasic sequence with biological half-lives of 1 and 24 days was determined. The results suggest that in general, iodine turnover in periwinkles is slower than observed for other molluscs (monophasic biological half-lives in the order of 2-3 days). Both environmental media, food and seawater, can be significant sources of radioiodine for the winkle.

Animals↗

Influence of material deprivation on hospital admissions for gynaecologic infections.

This study was conducted to examine the relationship between age, material deprivation, and hospital admissions for selected gynaecologic infections in an English health region. Data from hospital episode statistics relating to hospital admissions for pelvic inflammatory disease (PID), infections of the uterus, and infections of the cervix, vagina, and vulva were obtained. Townsend deprivation scores (based on 1991 census data) were allocated by linking postcodes of cases to enumeration districts (EDs) and then assigning the EDs to appropriate quintiles of material deprivation. Both single variable and multivariable (Poisson regression) analyses were performed. For women with PID, the risk of hospitalisation increased with increasing deprivation (P<0.0001), and women in the most deprived quintile were at increased risk (relative risk [RR] 1.31; 95% confidence interval [95%CI] 1.24-1.39) for hospitalisation. Multivariable analysis identified an elevated risk of hospital admission in women aged 25-44 years for PID (RR 2.03; 95%CI 0.84-4.87) and infections of the cervix, vagina, and vulva (RR 1.47; 95%CI 1.16-1.87), and the incidence of both conditions increased significantly with age. In summary, the results obtained suggest that women from the most deprived areas are at greatest risk of hospitalisation for gynaecologic infections, particularly PID. Preventive measures together with earlier diagnostic, treatment, and referral procedures are required to reduce morbidity.

Adolescent↗

Which patients spend more than 4 hours in the Accident and Emergency department?

OBJECTIVES: The NHS Plan has a target that no patient should spend longer than 4 hours in Accident and Emergency (A & E) by the end of 2004. The aim of this study is to describe the attendance characteristics of patients spending less than and more than 4 hours total time in A & E. METHODS: Data were collected from 10 A & E departments in the West Midlands NHS region for the period 1 April 2001 to 31 March 2002. Patients were split into three groups; those spending less than 4 hours, between 4 and 8 hours and over 8 hours in A & E. The groups were compared in terms of their attendance characteristics, these being demography, temporal patterns, arrival mode and disposal. The data were also entered into a multinomial logistic regression using SPSS. RESULTS: Overall, 83.0 per cent (range 76.7 - 94.0 per cent) of patients spent less than 4 hours in A & E ; 3.6% per cent (range 0.3-8.6 per cent) spent longer than 8 hours in A & E. The risk factors for spending over 4 hours in A & E were requiring admission, arriving by ambulance, arriving during the night, increasing age and higher levels of deprivation. Being admitted had the greatest effect on time spent in A & E, with a patient being 2.64 times more likely to spend 4-8 hours and 4.84 times more likely to spend over 8 hours in the department. CONCLUSIONS: This study points to admission and service provision at night as factors leading to long periods in A & E. However, these results can only act as a guide as the problems are different in different Trusts and each should analyse their problem before taking action.

Adolescent↗

Regional blockade for delivery in women with scoliosis or previous spinal surgery.

We conducted a prospective observational study between 1992 and 2001 identifying obstetric patients with untreated or surgically corrected scoliosis or lumbar-sacral fusion surgery. The regional techniques for labour and delivery that were offered were epidural analgesia, combined spinal epidural anaesthesia (CSE), single shot spinal or continuous spinal anaesthesia (CSA) depending on the degree of scoliosis, previous surgery, cardio-respiratory compromise and planned mode of delivery. Forty women were included in the study, one woman with two separate deliveries, giving 41 cases for analysis. Twenty-four women presented in labour: 11 required no regional technique, seven received effective epidural analgesia and six received CSA. Seventeen women presented for elective caesarean delivery: two received a CSE technique, two received single shot spinal and 13 had CSA. From a total of 19 CSA techniques attempted sixteen catheters were successfully inserted and produced good analgesia or anaesthesia for vaginal or operative delivery in 12 women (63%). There was one case of post dural puncture headache following a CSA for labour and delivery. We discuss the choices available for regional anaesthetic techniques in scoliotic women and the relative merits of each.

Journal Article↗

A novel semiquantitative polymerase chain reaction/enzyme digestion-based method for detection of large scale deletions/conversions of the CYP21 gene and mutation screening in Turkish families with 21-hydroxylase deficiency.

21-Hydroxylase deficiency is a recessively inherited disorder resulting from mutations in the CYP21 gene. The CYP21 gene is located along with the CYP21P pseudogene in the human leukocyte antigen major histocompatibility complex region on chromosome 6. Molecular diagnosis is difficult due to the 98% similarity of CYP21 and CYP21P genes and the fact that almost all frequently reported mutations reside on the pseudogene. Allele-specific PCR for the 8 most frequently reported point mutations was performed in 31 Turkish families with at least a single 21-hydroxylase-deficient individual. The allele frequencies of the point mutations were as follows: P30L, 0%; IVS2 (AS,A/C-G,-13), 22.5%; G110delta8nt, 3.2%; I172N, 11.4%; exon 6 cluster (I236N, V237E, M239K), 3.2%; V281L, 0%; Q318X, 8%; and R356W, 9.6%. Large deletions and gene conversions were detected by Southern blot analysis, and the allele frequencies were 9.6% and 22.5%, respectively. Sequence analysis of the gene, performed on patients with only 1 mutated allele, revealed 2 missense mutations (R339H and P435S). A novel semiquantitative PCR/enzyme digestion-based method for the detection of large scale deletions/conversions of the gene was developed for routine diagnostic purposes, and its accuracy was shown by comparison with the results of Southern blot analysis.

Adrenal Hyperplasia, Congenital↗

Apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) is a potentially fatal genetic disorder causing severe juvenile hypertension, pre- and postnatal growth failure, hypokalemia and low to undetectable levels of renin and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 (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. In 1998, a mild form of this disease was reported, which might represent an important cause of low-renin hypertension. Early and vigilant treatment might prevent or improve the morbidity and mortality of end-organ damage.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

Levobupivacaine for epidural analgesia in labor: the sparing effect of epidural fentanyl.

Evidence suggests that levobupivacaine has similar pharmacodynamic properties to racemic bupivacaine. We sought to investigate whether this similarity extends to opioid sparing when levobupivacaine is used for epidural analgesia in laboring women by quantifying the effect of fentanyl on the minimum local analgesic concentration (MLAC) of levobupivacaine. One-hundred-six women requesting epidural analgesia for labor pain were recruited in this randomized, double-blinded, up-down sequential allocation study. Each received 20 mL of one of three test solutions: levobupivacaine control, levobupivacaine and fentanyl 2 microg/mL, or levobupivacaine and fentanyl 3 microg/mL. The initial levobupivacaine concentration was 0.07% wt/vol in each group, with subsequent concentrations of levobupivacaine being determined by the response of the previous patient (testing interval 0.01% wt/vol). Efficacy was accepted if the visual analog score decreased to 10 mm or less on a 100-mm scale within 30 min. The MLAC of levobupivacaine in the control group was 0.091% wt/vol (95% CI, 0.052-0.130). Fentanyl at concentrations of 2 microg/mL and 3 microg/mL significantly reduced the MLAC of levobupivacaine to 0.047% wt/vol (95% CI, 0.023-0.072) and 0.050% wt/vol (95% CI, 0.035-0.065), respectively (P < 0.001). A dose-dependent effect was not demonstrated. We conclude that fentanyl significantly reduces levobupivacaine requirements for epidural analgesia in labor.

Adult↗

Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.

Congenital adrenal hyperplasia (CAH) refers to a family of monogenic inherited disorders of adrenal steroidogenesis most often caused by enzyme 21-hydroxylase deficiency (21-OHD). In the classic forms of CAH (simple virilizing and salt wasting), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Prenatal treatment of CAH with dexamethasone has been successfully used for over a decade. This article serves as an update on 532 pregnancies prenatally diagnosed using amniocentesis or chorionic villus sampling between 1978 and 2001 at New York Presbyterian Hospital-Weill Medical College of Cornell University. Of the 532 pregnancies, 281 were prenatally treated for CAH due to the risk of 21-hydroxylase deficiency. Follow-up telephone interviews with mothers, genetic counselors, endocrinologists, pediatricians, and obstetricians were performed in all cases. Of the pregnancies evaluated, 116 babies were affected with classic 21-OHD. Of these, 61 were female, 49 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 9 wk gestation (in proper doses) was effective in reducing virilization. There were no statistical differences in the symptoms during pregnancy between mothers treated with dexamethasone and those not treated with dexamethasone, except for weight gain, edema, and striae, which were greater in the treated group. No significant or enduring side-effects were noted in the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight from untreated, unaffected newborns. Based on our experience, prenatal diagnosis and proper prenatal treatment of 21-OHD are effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity, genital surgery, and possible sex misassignment.

Adrenal Hyperplasia, Congenital↗

Training in obstetric general anaesthesia: a vanishing art?

General anaesthesia in obstetric practice has largely been replaced by the use of regional techniques. We have studied this phenomenon and the subsequent impact on training in this technique both retrospectively and with a prospective audit. There has been a decline in the use of general anaesthesia for Caesarean section such that trainee anaesthetists are getting less practical exposure to this important procedure. Audit revealed a deficit with consultant involvement in training and heightened awareness has resulted in improved supervision. Possible implications for future consultant working practices are discussed.

Anesthesia, General↗

The ROOT MERISTEMLESS1/CADMIUM SENSITIVE2 gene defines a glutathione-dependent pathway involved in initiation and maintenance of cell division during postembryonic root development.

Activation of cell division in the root apical meristem after germination is essential for postembryonic root development. Arabidopsis plants homozygous for a mutation in the ROOT MERISTEMLESS1 (RML1) gene are unable to establish an active postembryonic meristem in the root apex. This mutation abolishes cell division in the root but not in the shoot. We report the molecular cloning of the RML1 gene, which encodes the first enzyme of glutathione (GSH) biosynthesis, gamma-glutamylcysteine synthetase, and which is allelic to CADMIUM SENSITIVE2. The phenotype of the rml1 mutant, which was also evident in the roots of wild-type Arabidopsis and tobacco treated with an inhibitor of GSH biosynthesis, could be relieved by applying GSH to rml1 seedlings. By using a synchronized tobacco cell suspension culture, we showed that the G(1)-to-S phase transition requires an adequate level of GSH. These observations suggest the existence of a GSH-dependent developmental pathway essential for initiation and maintenance of cell division during postembryonic root development.

Alleles↗

Steroid disorders in children: congenital adrenal hyperplasia and apparent mineralocorticoid excess.

Our research team and laboratories have concentrated on two inherited endocrine disorders, congenital adrenal hyperplasia (CAH) and apparent mineralocorticoid excess, in thier investigations of the pathophysiology of adrenal steroid hormone disorders in children. CAH refers to a family of inherited disorders in which defects occur in one of the enzymatic steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex. The majority of cases is due to 21-hydroxylase deficiency (21-OHD). Owing to the blocked enzymatic step, cortisol precursors accumulate in excess and are converted to potent androgens, which are secreted and cause in utero virilization of the affected female fetus genitalia in the classical form of CAH. A mild form of the 21-OHD, termed nonclassical 21-OHD, is the most common autosomal recessive disorder in humans, and occurs in 1/27 Ashkenazic Jews. Mutations in the CYP21 gene have been identified that cause both classical and nonclassical CAH. Apparent mineralocorticoid excess is a potentially fatal genetic disorder causing severe juvenile hypertension, pre- and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11beta-hydroxysteroid dehydrogenase type 2. In 1998, we reported a mild form of this disease, which may represent an important cause of low-renin hypertension.

Adrenal Hyperplasia, Congenital↗

Variations in admissions to hospital for head injury and assault to the head. Part 1: Age and gender.

The study retrospectively investigated variations in the use of secondary healthcare for head injury, particularly assault. A total of 25,300 emergency head-related admission were examined over a two-year period, of which 3756 were for assault. More males were admitted during summer and holiday periods, while there were fewer female patients with head injuries and the incidence varied less. The largest number of admissions was among men aged 15-44 and most assaults occurred at weekends. Females were more likely than males to die from all head injuries (OR=1.31) and violent head injuries (OR=2.38). Women (15+) stayed longer in hospital than males. Injuries among males are primarily associated with social occasions. Females experience head injuries all the year round suggesting that these injuries are the result of domestic violence. There are important demographic differences in numbers of patients and duration of hospital care required to treat these avoidable injuries.

Adolescent↗