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Biomedical subjects

C R West

Publications and source records attributed to C R West.

At least 19 recordsLinked to original sources
PubMed2006

Cardiorenal effects of celecoxib as compared with the nonsteroidal anti-inflammatory drugs diclofenac and ibuprofen.

The cardiorenal safety database from the Celecoxib Long-term Arthritis Safety Study (CLASS) was analyzed to examine whether supratherapeutic doses of celecoxib are associated with decreased renal function and blood pressure (BP) effects compared with standard doses of diclofenac and ibuprofen in osteoarthritis (OA) and rheumatoid arthritis (RA) patients.In total, 8059 patients were enrolled; 7968 received at least one dose of study drug (RA: N = 2183; OA: N = 5785). Patients received celecoxib, 400 mg twice a day (b.i.d.). (N = 3987); ibuprofen, 800 mg three times a day. (N = 1985); or diclofenac, 75 mg b.i.d. (N = 1996). Effects measured included: investigator-reported hypertension, edema or congestive heart failure, clinically important BP elevations, incidence of patients starting new antihypertensive medication, and increases in serum creatinine or reductions in creatinine clearance. Celecoxib was associated with a similar incidence of hypertension or edema to diclofenac but significantly lower than ibuprofen. The celecoxib group had significantly fewer initiations of antihypertensives versus ibuprofen. Systolic BP increases of >20 mmHg and above 140 mmHg occurred significantly less often with celecoxib compared with ibuprofen or diclofenac. Changes in serum creatinine or estimated creatinine clearance occurred in a similar percentage of patients taking celecoxib or ibuprofen; modest differences were evident against diclofenac. In patients with mild prerenal azotemia, significantly fewer patients taking celecoxib exhibited clinically important reductions in renal function (3.7%), compared with diclofenac (7.3%; P < 0.05) and ibuprofen (7.3%; P < 0.05). A supratherapeutic dose of celecoxib was associated with an improved cardiorenal safety profile compared with standard doses of either ibuprofen or diclofenac.

Acid-Base Equilibrium↗
PubMed2005

Feasibility and safety of early transfer of premature infants from incubators to cots: a pilot study.

OBJECTIVES: To document whether medically stable infants can be transferred safely from incubators to unheated, open cots at 1500 g. METHODS: Four cohorts were recruited in a stepwise observational trial of transfer from incubators to unheated, open cots. We aimed to transfer the first 15 infants into cots on reaching a weight of 1800 g, the second at 1700 g, the third at 1600 g and the fourth at 1500 g. Nursery temperatures were set at 25 degrees C. The primary outcome measure was failure of transfer defined as the inability to maintain body temperatures in a cot despite additional coverings, with two consecutive axillary temperatures below 36.6 degrees C 1 h apart. Secondary aims were to determine temperature stability, growth, medical complications and time to discharge for these infants. Weight and corrected gestation at discharge were recorded. RESULTS: A total of 61 infants were recruited and transferred into cots. Cohorts were similar in gestation and sex. Infants recruited to the 1500 g cohort had higher birthweights than the other cohorts. There was no difference in the rate of infants failing transfer into cots between cohorts. Rate of weight gain before and after transfer and the number of high and low temperatures per infant after transfer was not different between cohorts. There were no differences between cohorts for discharge weight or corrected gestation. CONCLUSIONS: The results of this pilot study indicate the potential to transfer very low birthweight infants to an open unheated cot at a bodyweight of 1500 g. This study provides information for the design of future randomized controlled trials that are required to confirm the findings of this study before routine adoption of this intervention into clinical practice.

Body Temperature Regulation↗
PubMed2004

Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27.

Heat shock protein 27 (hsp-27) is a regulator of oestrogen receptor (ER) expression and a modulator of intracellular homeostasis. In this laboratory, Shaaban et al demonstrated the importance of ER-alpha, together with Ki67, in enhancing the progression of benign breast lesions of defined morphological types. To better understand the mechanisms by which ER-alpha promotes breast neoplasia, this study was performed to test the hypothesis that the roles of ER-alpha and hsp-27 may be defined by their quantitative expression in proliferative breast lesions of varying histological risk. The expression of hsp-27 was identified using a specific monoclonal antibody and analysed to assess the proportion of positive epithelial cells using digitised morphometric image analysis. The expression of ER-alpha was analysed by immunohistochemistry and Western blotting in a variety of benign (HUMA121) and malignant mammary cell lines, including ER-alpha(+) (MCF7, ZR-75, T47D) and ER-alpha(-) (MDA-MB 231) breast cancer cell lines. The data confirm that, during progression from normal through proliferative breast lesions to in situ cancer, there was a significant increase in both the proportion and the optical density of the epithelial cells expressing hsp-27. The mean levels of expression ranged from 7.4% of the total number of epithelial cells in normal lobules to 25.17% of epithelial cells in hyperplasias of usual type (HUT) to 61.1% of epithelial cells in ductal carcinoma in situ (P<0.001). The study has confirmed the expression of hsp-27 to be closely associated with ER-alpha(+) expression, and that its regulated expression occurs early along the mammary oncogenic pathway, supporting the initial hypothesis. It is our proposal that the differential expression of hsp-27 modulates the phenotypic behaviour of morphologically benign epithelial cells and hence may be an important determinant in initiating, or promoting, a population of human mammary cancers.

Biomarkers, Tumor↗
PubMed2004

S100A4 regulates cell motility and invasion in an in vitro model for breast cancer metastasis.

Elevated levels of the calcium-binding protein S100A4 are associated with poor patient survival in breast cancer patients and induce metastasis in rodent models. To investigate the effects of S100A4 on different components of the metastatic process, epithelial cells lines have been isolated from nonmalignant tumours in neu transgenic mice and from malignant tumours in neu/S100A4 double transgenic mice. Additional cell lines expressing both Neu and S100A4 have also been derived by transfection of rat S100A4 cDNA into tumour cell lines cloned from neu single transgenic mice. Using these cells in transfilter migration assays, it has been shown that increases in either motility or invasive properties correlate with each other and with the level of S100A4 protein. Injection of three of the cell lines separately into the mammary fat pads of nude mice showed that elevated levels of S100A4 correlated with the degree of metastasis to the lungs. In contrast, changes in cell proliferation and cell-substrate adhesion did not correlate with S100A4 levels. Neither motility nor invasiveness correlated with proteolytic degradation of gelatin as measured by zymography. Thus, the results suggest that the main effect of increases in S100A4 levels in metastasis is to generate increased cell motility and invasion and that this latter change is not dependent upon an increased ability to degrade the intercellular matrix.

Animals↗
PubMed2004

Maternal water intoxication as a cause of neonatal seizures.

A term infant was admitted at 6 h of age with seizures related to hyponatraemia. During the last hours of labour the infant's mother had drunk 3 L of water. After delivery the serum sodium was 121 mmol/L in the mother and 126 mmol/L in the infant. Both resolved spontaneously. We discuss this case and the impact of maternal fluid intake during labour on the fetus and neonate. Women should be advised that excessive oral fluid intake during labour could adversely affect both mother and infant.

Female↗
PubMed2003

Socioeconomic variation in colon cancer tumour factors associated with poorer prognosis.

Analysis of population-based registry data (n=7393) showed that more deprived colon cancer patients had lower risk of the mucin-producing adenocarcinoma subtype, proximal subsite (to the descending colon), and no greater risk of high-grade tumours. Tumour factors therefore appear unlikely to account for socioeconomic gradients in survival.

Adenocarcinoma, Mucinous↗
PubMed2003

Lung function and respiratory health in adolescents of very low birth weight.

AIMS: To determine if very low birth weight (VLBW; birth weight <1500 g) is associated with reduced lung function and respiratory health in adolescence and, if it is, whether this impairment is associated with prematurity or intrauterine growth restriction. METHODS: A geographically defined cohort of 128 VLBW infants and an age, sex, and school matched comparison group born in 1980/81 were studied. The cohort and comparison group were assessed at 15 years of age. The birth weight ratio of the index cases (observed birth weight/expected birth weight for the gestation) was determined to assess the degree of growth restriction. Respiratory support received during the neonatal period was obtained from hospital records. Smoking habits and respiratory morbidity were obtained through questionnaires. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and forced expiratory flow when 25-75% of FVC is expired (FEF(25-75%)) were measured using a portable spirometer. The values are expressed as percentage predicted for height, age, and gender using standard reference values. Adjustments were made for smoking habits of mother and children. RESULTS: The differences in means between index and comparison groups for FEF(25-75%) (-12.42%; p < 0.001) and FEV1/FVC (-3.53%; p < 0.001) ratio were statistically significant. The differences in FVC and FEV1 were not significant. No correlation was found between the birth weight ratio and lung function among the index cohort. Chronic cough, wheezing, and asthma were more common among the index cohort than in the comparison group. Within the index group, there was no difference in lung function between those who received and those who did not receive respiratory support. CONCLUSION: Adolescents who were VLBW compared with matched controls showed medium and small airways obstruction. This was associated with prematurity rather than intrauterine growth restriction or having received respiratory support during the neonatal period. The index VLBW cohort compared with their controls were also more prone to chronic cough, wheezing, and asthma.

Adolescent↗
PubMed2003

General Certificate of Secondary Education performance in very low birthweight infants.

AIM: To compare children of very low birth weight with matched controls for their performance in the General Certificate of Secondary Education (GCSE). METHODS: GCSE examination results of 167 children of birth weight < or =1500 g attending mainstream schools and without clinical disability and 167 individually matched classroom controls were analysed. RESULTS: In 143 instances, both children of a matched pair were entered for examination in one or more GCSE subjects. The total points score obtained was greater in the comparison group than in the index cases (difference between means 4.45: 95% CI 0.95 to 7.94; p = 0.01). The mean point score per examination subject was also significantly greater in the comparison group than in the index cases (mean of differences 0.43: 95% CI 0.12 to 0.73; p < 0.01). CONCLUSIONS: As the children were closely matched for school and several social variables, factors acting during fetal or early postnatal development of very low birthweight infants probably compromise performance in the GCSE examination to a greater extent than school or childhood social environmental factors.

Achievement↗
PubMed2002

Histopathologic types of benign breast lesions and the risk of breast cancer: case-control study.

The hypothetical multistep model of carcinogenesis indicates that breast cancer develops via a series of intermediate hyperplastic lesions through in situ to invasive carcinoma. To identify the risk inherent within the different morphologic lesions, we have analyzed the data from 674 benign biopsy specimens comprising 120 cases who subsequently developed breast cancer and 382 controls (matched for age and date of biopsy) spanning a period up to 20 years of follow-up (mean 66.95 months). In this series we have confirmed an increased risk associated with certain types of benign breast lesions. Atypical lobular hyperplasia was the most significant risk factor for breast cancer with more unfavorable outcome in patients <50 years of age (p = 0.003) and a relative risk (RR) of 4.55 (confidence interval [CI] 1.77-11.69). Hyperplasia of usual type showed an RR of 1.53 (CL 1.10-2.13) with a statistically worse probability of survival (cancer-free time) for patients >50 years. For atypical ductal hyperplasia the RR was 2.03 (CI 0.80-1.39). Blunt duct adenosis was significantly more common in cases progressing to breast cancer compared with controls, showing an RR of 2.08 (CI 1.12-2.85). We describe in detail the criteria of morphologic changes observed in blunt duct adenosis and define, for the first time, the level of risk associated with each of its six subtypes. Improved knowledge of breast carcinogenesis will provide insight for defining high-risk groups thus resulting in improved screening and management regimens.

Age Factors↗
PubMed2001

Dermatoglyphic patterns, very low birth weight, and blood pressure in adolescence.

AIMS: To test the null hypotheses that finger and palm prints have no relation with fetal growth or adolescent blood pressure. METHODS: All 128 singleton, unimpaired, very low birth weight (VLBW; < or =1500 g) infants born to mothers resident in the county of Merseyside in 1980 and 1981 were studied retrospectively. The comparison group consisted of 128 age, sex, and school matched children. Main outcome measures were blood pressure at age 15 years, birth weight ratio, fingerprint patterns, and palmar AtD angles. RESULTS: The VLBW index population had a significantly higher systolic blood pressure than the comparison group (mean difference 3.2 mm Hg). The difference in diastolic blood pressure between the VLBW index and the matched comparison group was not significant. No significant differences were found in the palmar AtD angles or in the fingerprint proportions of arches, loops, and whorls and no correlation was found between fingerprint patterns and blood pressure. Among the VLBW index population, both height and right palmar AtD angle were independently and significantly correlated with and explained 12.1% of the variance in the systolic blood pressure. Birth weight ratio, as a measure of fetal growth restriction, had no significant correlation with systolic blood pressure. CONCLUSIONS: The higher systolic blood pressure of adolescents who were of very low birth weight compared with the matched comparison group is not associated with fingerprint patterns or birth weight ratio as markers for fetal growth restriction.

Adolescent↗
PubMed2000

A biomechanical study of the human vertebral artery with implications for fatal arterial injury.

We studied the biomechanical behaviour of ring and strip specimens from along the length of 18 vertebral arteries taken from 16 subjects aged 28-90 years, in order to consider some of the factors which may play a role in vertebral artery rupture. The method was chosen to allow a comparison between circumferential distension (ring samples) and longitudinal extension, (strip samples). The samples were extended between the jaws of a tensile testing apparatus until the specimen broke and a number of biomechanical parameters were derived. These were the percentage extension to break, the tensile strength, Young's modulus and the peak load. There were a number of important findings. The vertebral artery was shown to be susceptible to longitudinal stretching with a number of strip samples breaking when extended by as little as 16-20%. The tensile strength and load at peak of the strip specimens were correspondingly lower than for the ring samples. Marked intersubject variations were shown for all these parameters and prominent changes in behaviour occurred along the vertebral artery. This study indicates that the artery may be susceptible to head and neck movements which cause the vessel to stretch, and intersubject variations in behaviour may be one important explanation for the marked differences in outcome which appear to exist in subjects who suffer broadly similar head and neck insults.

Adult↗
PubMed2000

Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer.

Our aim was to compare the occurrence and prognostic significance over 14-20 years of immunocytochemically detected S100A4 and other tumour variables in primary tumours from 349 patients with operable breast cancer. For a cut-off of 1% staining of the malignant cells, the antibody to S100A4 stains positively 56% of the carcinomas. There was a significant association of staining for S100A4 with tumours fixed to the chest wall, staining for c-erbB-2, c-erbB-3, pS2, cathepsin D and, inversely, at borderline levels with staining for estrogen receptor. Using Wilcoxon statistics in univariate analyses, staining for S100A4, nodal status, tumour class, histological grade and staining for c-erbB-2, p53 were associated negatively and staining for estrogen receptor, progesterone receptor were associated positively with patient survival times. The survival times of patients with S100A4-negative carcinomas with or without one of the other tumour variables showed no significant differences, whilst those of patients with S100A4-positive carcinomas showed significant differences in a negative or a positive way. Multivariate regression analysis for 137 patients showed that staining for S100A4 is most highly correlated with patient deaths, but involved lymph nodes, fixed tumours, high histological grade and staining for progesterone receptor were also significant independent prognostic variables. Our results suggest that in this set of patients, the tumour variable most tightly correlated with patient death is S100A4.

Adult↗
PubMed2000

Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer.

The calcium-binding protein S100A4 is capable of inducing metastasis in rodent models for breast cancer. We now show that rabbit antibodies to recombinant rat S100A4 recognize specifically human S100A4 using Western blotting techniques and use them to assess the prognostic significance of S100A4 in primary tumors from a group of 349 patients treated between 1976 and 1982 for stage I and stage II breast cancer. The antibody stains normal breast tissue heterogeneously, but stains positively 41% of the carcinomas, leaving the remaining 59% as negatively stained. In addition to the carcinoma cells, some host stromal cells and lymphocytes are also stained, but these have been discounted in subsequent analyses. There is an association of staining of carcinomas for S100A4 with some tumor variables considered to be associated with poor prognosis for patients: tumor present in axillary lymph nodes (borderline P = 0.058), staining for c-erbB-3 (P = 0.002), cathepsin D (P = 0.024), and c-erbB-2 (P = 0.048). The association of staining for S100A4 with patient survival has been evaluated using life tables and analyzed using generalized Wilcoxon statistics. Eighty percent of the S100A4-negative patients but only 11% of the S100A4-positive patients are alive after 19 years of follow-up, and this association is highly significant (P < 0.0001); the former have a median survival of >228 months and the latter 47 months. The other tumor variables that show significant association with survival time are nodal status (P < 0.0001), tumor size (P = 0.0035), histological grade (P = 0.013), staining for c-erbB-2 (P = 0.0015), estrogen receptor (P = 0.028), and p53 (P = 0.032). Analysis of the association of patients with carcinomas staining for S100A4 and their survival in subgroups defined by these other tumor variables shows that in each subgroup, staining for S100A4 is associated with poorer survival. Patients whose tumors stain for S100A4 and possess involved lymph nodes (P < 0.0001), which are fixed to the chest wall (P = 0.015) or which stain for c-erbB-2 (P = 0.050), show a significant reduction in survival times over those with only S100A4-staining tumors. Patients with involved lymph nodes, or staining for c-erbB-2 in the S100A4-negative group fail to show any significant reduction in survival times. Multivariate regression analysis for 137 patients shows that staining for S100A4 is most highly correlated with patient deaths (P < 0.0001), but involved lymph nodes (P = 0.001), fixed tumors (P = 0.0002), and high histological grade (P = 0.022) are also significant independent prognostic variables. These results suggest that in this group of patients, the metastasis-inducing protein S100A4 is most tightly correlated with patient demise.

Adult↗
PubMed1999

Survival and patterns of recurrence in 200 oral cancer patients treated by radical surgery and neck dissection.

The outcome of 200 patients with squamous cell carcinoma of the oral/oropharyngeal mucosa managed by primary radical surgery and simultaneous neck dissection and followed for 2.2-8.5 years is reported and related to the pathological features. Ninety-nine patients (50%) had cervical lymph node metastases including 16 (8%) with bilateral metastases. Actuarial (life tables) survival analysis showed the overall 2-year survival probability was 72%, falling to 64% at 5 years. The 5-year survival probability was 81% for patients without metastasis, 64% for patients with intranodal metastases and 21% for patients with metastases showing extracapsular spread. A total of 60 patients (30%) died of/with their cancer: 36 (18%) of local recurrence; 4 (2%) of a metachronous primary tumour; 14 (7%) of regional disease, and 6 (3%) with systemic metastases. A further 15 patients (8%) had relapsed but were clinically disease-free after additional surgery. In all, 7% of the series developed metachronous primary tumours. In addition to nodal metastasis, survival was related to the site and stage of the primary tumour, the histological grade and pattern of invasion, status of the resection margins and pathological TNM stage. For patients with lymph node metastasis, extracapsular spread was an important indicator of tumour behaviour and we recommend its use as a criterion for pathological N staging.

Adult↗
PubMed1999

Fetal and infant death in mono- and dizygotic twins in England and Wales 1982-91.

AIM: To quantify the level of risk for stillbirth and infant death in singleton compared with twin pregnancies, using national data; to determine the independent effects of zygosity, sex, and birthweight on these risks in twin pregnancies. METHODS: A retrospective national study was carried out of all singleton and twin birth and death registrations in England and Wales 1982-91, according to sex and birthweight group. Weinberg's rule was applied to the twin pairs to differentiate mono- from dizygotic twins. Relative risks for mono- compared with dizygous twins for both twins being stillbirths and for one of the pair being a stillbirth were determined. For twins where one was stillborn and the other live born, the relative risk of neonatal and infant mortality in the surviving co-twin was determined. RESULTS: There were 6 563 834 registered singletons and 70772 registered twin pairs for the period under study. Monozygotic twins had a relative risk of: 18.91 (95% CI 12.48-28.64) for both twins being stillborn; 1.63 (95% CI 1.48-1.79) for one twin being a stillbirth; and 2.26 (95% CI 1.45-3.52) for the live born co-twin dying as a neonate. When both twins were live born and among singletons, the odds ratio for neonatal mortality of being male was 1.41 (95% CI 1.37-1.45) and there was a highly significant negative association with birthweight. After adjusting for birthweight group and sex, twins had a reduced neonatal mortality compared with singletons: odds ratio 0.91 (95% CI 0.85-0.96). CONCLUSIONS: Fetal death in one of monozygotic twins has serious implications for survival of the co-twin. Monochorionicity is probably the essential feature of the increased risk to the co-twin. It is imperative that all fetal deaths in multiple pregnancies are recorded and chorionicity determined if parents are to be adequately counselled.

Birth Weight↗
PubMed1998

Association of blood pressure in adolescence with birthweight.

AIMS: To compare the blood pressure of very low birthweight infants with that of normal birthweight controls in adolescence. METHODS: A cohort of all infants of birthweight < or = 1500 g born to women resident in the county of Merseyside in 1980-1 was followed up at age 15 years with age, sex, and school matched controls. Growth indices and blood pressures were measured under standard conditions. The smoking history of mothers and children and their status for several socioeconomic variables were documented. In a matched pairs analysis systolic and diastolic blood pressures were compared for cases and controls before and after adjusting for height, weight, and body mass index. RESULTS: There were 172 singleton 15 year old survivors of birthweight < 1500 g out of 40,321 live births of Merseyside residents in 1980-1. Of the 172 survivors, 128 (74%) who had no clinical disability and 11 (6%) with a clinical disability but attending normal schools, were assessed with individually matched age, sex, and school controls. Twenty three (13%) had a clinical disability and were attending special schools; these were assessed without controls. Ten (6%) children refused or were unavailable for assessment. The systolic blood pressure was significantly higher in cases than in controls; the mean of the difference was 3.2 mm Hg. The diastolic blood pressure was also higher in the cases, but the difference was not significant. The controls were significantly heavier (4.4 kg), taller (4.0 cm), with larger head circumference (1.5 cm) than the cases. The difference in body mass index was not significant. Adjusting for height, weight, or body mass index increased the difference in systolic blood pressure between cases and controls. There were no significant differences in the socioeconomic variables, but what differences did exist favoured the controls. There was also a higher prevalence of smoking among the children and the mothers of the cases than the controls. CONCLUSIONS: The study supports the hypothesis that in adolescents variation in systolic blood pressure has its origins in fetal development. Some of the variation could be attributed to socioeconomic differences.

Adolescent↗
PubMed1997

Regulation of growth hormone-releasing hormone and somatostatin from perifused, bovine hypothalamic slices. I. Alpha 2-adrenergic receptor regulation.

An in vitro perifusion system was developed for bovine hypothalamic tissue to examine the role of alpha 2-adrenergic receptors in the regulation of growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) release. Up to three sagittal slices (600 microns) of hypothalamus, immediately parallel to the midline, were cut in an oxygenated balanced salt solution at 4 degrees C, placed in 5 cc syringes, and perifused at 37 degrees C with oxygenated minimum essential medium-alpha at a flow rate of 0.15 ml/min. Three experiments were conducted, and medium effluent was collected every 20 min before (two samples), during (one or three samples), and after (six samples) treatment. Areas under GHRH and SRIF response curves (AUC), adjusted by covariance for pretreatment values, were calculated from samples collected during the treatment/post-treatment period. Location from which slices were cut, relative to the sagittal midline, had no effect on basal release of GHRH and SRIF, but variation in basal release of GHRH and SRIF differed among animals. Medium containing 60 mM KCI increased AUC for GHRH 39% and 161% for SRIF when compared with perifusion of medium alone, thereby verifying that tissue remained viable for at least 14 hr. Activation of alpha 2-adrenergic receptor with 10(-6) and 10(-4) M clonidine increased AUC for GHRH from 54.8 (control) to 79.1 and 108.7 +/- 2.5 ng.ml-1 min for 10(-6) M and 10(-4) M clonidine, respectively. Guanabenz, another alpha 2-adrenergic receptor agonist, at 10(-8), 10(-6), and 10(-4) M also increased GHRH release from 45.5 (control) to 52.8, 66.2, and 86.7 +/- 1.6 ng.ml-1 min, respectively. Clonidine and guanabenz did not affect release of SRIF. An alpha 2-adrenergic receptor antagonist, idazoxan, blocked clonidine-induced release of GHRH without affecting release of SRIF. We concluded that alpha 2-adrenergic receptor stimulation of in vivo growth hormone secretion in cattle is mediated via an increase in release of GHRH and not a change in release of SRIF.

Adrenergic alpha-Agonists↗