Search PubMed⌕ Search

Biomedical subjects

C Wright

Publications and source records attributed to C Wright.

At least 19 recordsLinked to original sources
PubMed2000

Changing pattern of expression of parvalbumin immunoreactivity during human fetal spinal cord development.

Expression of the calcium binding protein parvalbumin (PV) by different classes of spinal neuron has been shown to be developmentally regulated in both rat and monkey. From postmortem studies of eight human cervical spinal cords ranging in age from 11 to 35 weeks postconceptional age, we report that parvalbumin immunoreactivity is similarly plastic in human lower cervical spinal cord development, with many changes occurring prenatally. At 11-14 weeks postconceptional age, there was prominent immunostaining of primary sensory afferents that could be seen coursing through the dorsal horn and extensively innervating the motoneuron pools. Motoneurons were also found to be clearly immunoreactive for choline acetyltransferase by this age. A few ventral horn neurons that were not motoneurons were also parvalbumin immunoreactive. By 24-27 weeks postconceptional age, sensory afferents were still immunoreactive, as were many other axons throughout the white matter. In addition, many ventral horn neurons were now immunoreactive as well as a few dorsal horn neurons. By 31-35 weeks postconceptional age, there was extensive immunostaining of neurons throughout the spinal cord, including a few moderately immunoreactive motoneurons. There were many immunopositive axons in all the white matter tracts except the corticospinal tracts; however, staining of sensory axons traversing the grey matter was less prominent by this age. In the rat, expression of PV by primary sensory neurons coincides with the onset of fetal limb movement. The onset of expression of PV in ventral horn neurons coincides with later developmental events after the arrival of corticospinal inputs, whereas widespread PV immunoreactivity in dorsal horn neurons marks the attainment of a mature pattern of PV expression. The extent to which expression of PV immunoreactivity can be taken to indicate landmarks in human development will be discussed.

Age Factors↗
PubMed2000

Are there gender differences in patients presenting with unstable angina?

BACKGROUND: There are limited studies on gender differences in patients with unstable angina. We investigated the influence of gender in these patients in a tertiary referral centre. METHODS AND RESULTS: Three hundred and thirteen consecutive patients (210 men and 103 women) with unstable angina were studied over a 42-month period. Patient characteristics, cardiovascular risk factors and subsequent management including coronary artery bypass graft (CABG) operation and percutaneous transluminal coronary angioplasty (PTCA) were investigated. There was no difference in age [61.6 (11.0) (S.D.) years for men vs. 63.5 (10.5) years for women]. Diabetes mellitus and hypertension were more common in women (diabetes, 11% vs. 23%, P = 0.007; hypertension, 32% vs. 52%; P = 0.001). The number of smokers was greater in men (73% vs. 46%, P = 0.00001). There was no difference in the prevalence of hypercholesterolaemia or in the incidence of previous myocardial infarction, previous history of angina and family history of ischaemic heart disease. The duration of unstable angina before presentation to the referring hospital was similar in both sexes. The use of aspirin, intravenous heparin and antianginal drugs was also comparable in the two genders. The number of coronary arteries involved in men and women appeared similar (one vessel, 22% vs. 27%; two vessels, 26% vs. 21%; three vessels, 52% vs. 52% in men and women, respectively). The proportion of men and women who underwent subsequent revascularisation was also similar (CABG, 31% vs. 33%; PTCA, 42% vs. 40%). The overall in-hospital mortality was higher in women (6.8% vs. 2.8%), but was not statistically significant (P = 0.18). CONCLUSIONS: Gender differences in unstable angina manifest in the preponderance of selected risk factors including diabetes mellitus and hypertension in women and smoking in men. There is no difference in age, the degree of coronary artery involvement and the subsequent management in a tertiary referral centre.

Angina, Unstable↗
PubMed2000

Pemphigus vulgaris of the uterine cervix revisited: case report and review of the literature.

Pemphigus vulgaris is an autoimmune disease characterized by acantholytic blisters and erosions involving the oral mucosa, skin, and less frequently other mucosal surfaces. Although the cytology of scrapings from the cutaneous and oral lesions has been well-documented, there are relatively few reports in the literature of the cytologic appearance of pemphigus on cervicovaginal smears. This report documents a case of pemphigus involving the cervix, in which the diagnosis was not known at the time of the cervical smear and biopsy. The cytologic features of this case and those in the literature are described in detail, highlighting the necessity of awareness of the disease and its presentation on cervicovaginal smears, in preventing an overdiagnosis of neoplasia.

Adult↗
PubMed2000

Failure to thrive in a population context: two contrasting studies of feeding and nutritional status.

Although failure to thrive (FTT) is generally thought to be a nutritional problem, dietary intake in children with FTT has been little researched. We describe two community-based studies of dietary intake and eating behaviour in FTT. The first study of ninety-seven children with FTT identified by population screening found that only a minority of case children were associated with neglect, organic illness or deprivation, even though dietary information suggested an underlying nutritional cause in the majority. Limited case-control data suggested significantly delayed weaning and less liking for food in general among the case children. The second study found diminished appetite, delayed progression onto solid foods and fewer foods eaten by forty-four children referred with FTT compared with forty-five controls, but was unable to detect a significant difference in energy intake, even allowing for varying body composition and other confounding variables. This study also revealed the bias introduced by recruiting case children by referral rather than screening, and that despite rigorous matching procedures the controls were not representative of the general population. These studies suggest a wide range of differences in eating behaviour and feeding patterns between children with FTT and controls, but suggest that measurements of nutrient totals may not be robust. Studies of FTT based on referred children can be misleading, as can comparison with controls, unless allowance can be made for important confounding social variables.

Diet↗
PubMed2000

Risk factors for failure to thrive: a population-based survey.

AIM: To identify whether differences exist between failure to thrive children and controls in either demographic characteristics or parental rating of their eating and other behaviour. METHODS: As part of an intervention study, 97 children with failure to thrive were identified by population screening and received a standardized assessment by their health visitor at a median age of 15.1 months. This included standard questions to parents concerning their perception of their child's feeding history and behaviour. Their responses were compared with the parents of 28 normally growing children aged 16-18 months, systematically sampled from the same district. RESULTS: Cases had fallen through a mean of 1.69 weight standard deviation score and were markedly underweight for height. The case families had similar levels of deprivation, both to controls and city norms, and only four showed evidence of major neglect. Failure to thrive children had significantly more infancy feeding problems and were introduced to solids and finger foods later than controls; they were significantly more often described as variable eaters, undemanding and shy and less often as hungry. Cases liked most foods, but significantly less so than controls. CONCLUSIONS: This suggests that the role of deprivation and neglect has been overstated and that undemanding behaviour, low appetite and poor feeding skills may contribute to the onset and persistence of failure to thrive.

Failure to Thrive↗
PubMed2000

NMR investigations of protein-carbohydrate interactions binding studies and refined three-dimensional solution structure of the complex between the B domain of wheat germ agglutinin and N,N', N"-triacetylchitotriose.

The specific interaction of the isolated B domain of wheat germ agglutinin (WGA-B) with N,N',N"-triacetylchitotriose has been analyzed by 1H-NMR spectroscopy. The association constants for the binding of WGA-B to this trisaccharide have been determined from both 1H-NMR titration experiments and microcalorimetry methods. Entropy and enthalpy of binding have been obtained. The driving force for the binding process is provided by a negative DeltaH which is partially compensated by negative DeltaS. These negative signs indicate that hydrogen bonding and van der Waals forces are the major interactions stabilizing the complex. NOESY NMR experiments in water solution provided 327 protein proton-proton distance constraints. All the experimental constraints were used in a refinement protocol including restrained molecular dynamics in order to determine the refined solution conformation of this protein/carbohydrate complex. With regard to the NMR structure of the free protein, no important changes in the protein NOEs were observed, indicating that carbohydrate-induced conformational changes are small. The average backbone rmsd of the 35 refined structures was 1.05 A, while the heavy atom rmsd was 2.10 A. Focusing on the bound ligand, two different orientations of the trisaccharide within WGA-B binding site are possible. It can be deduced that both hydrogen bonds and van der Waals contacts confer stability to both complexes. A comparison of the three-dimensional structure of WGA-B in solution to that reported in the solid state and to those deduced for hevein and pseudohevein in solution has also been performed.

Amino Acid Sequence↗
PubMed2000

Sudden death in children and adolescents.

OBJECTIVE: To identify the incidence, causes, and characteristics of sudden death at age 1-20 years. DESIGN: A review of all deaths at age 1-20 years. Death certificates were obtained from the Office for National Statistics, and further information, where appropriate, from coroners, paediatricians, physicians, and pathologists. SETTING: The resident population of one English health region in 1985-1994. RESULTS: In a population of 806 500 children and adolescents aged 1-20 years there were 2523 deaths in 10 years. Medical causes accounted for 1017 deaths (40%); 1236 (49%) were unnatural, and 270 (11%) were sudden. These sudden deaths comprised 142 with a previous diagnosis, the commonest being epilepsy 49 (34%), cardiovascular disease 33 (23%), and asthma 30 (21%); 87 attributed to a cause discovered at necropsy, which was respiratory infection in 32 (37%), other infections in 17 (20%), and unsuspected cardiovascular abnormalities in 26 (30%); 41 remained unexplained. CONCLUSIONS: Half of all sudden deaths in children or adolescents were attributed to an already diagnosed condition. Abnormalities identified at necropsy accounted for one third of sudden deaths. Undiagnosed hypertrophic cardiomyopathy caused less than one death per million person years in the population aged 1-20 years. Unexplained sudden death, which may be caused by primary cardiac arrhythmia, is probably about 10 times more common.

Adolescent↗
PubMed2000

Congenital diaphragmatic herniation: antenatal detection and outcome.

201 fetuses and babies with a congenital diaphragmatic herniation or eventration (referred to collectively as CDH) were notified to the Northern Region Congenital Abnormality Survey (NorCAS) in the 13-year period from 1985 to 1997, an incidence of 0.25 per 1000 births. The 1-year survival of all pregnancies associated with CDH was 37%. The 1-year survival of livebirths was 50%. Antenatal scan detected the diaphragmatic defect or associated structural abnormality in 50%. Another major structural abnormality was present in 62 (31%); one of these babies survived and 26 pregnancies were terminated. This group contained four of the six antepartum stillbirths, all three intrapartum stillbirths and four of the five spontaneous miscarriages. Non-isolated CDH occurred in association with Fryns (5), Goldenhar (1) and de Lange (1) syndromes, and in 16 of 17 with a chromosome anomaly. 53% of the 139 fetuses with isolated CDH survived to 1 year of age, and 59% of the 124 liveborn survived. Of 37 fetuses with isolated CDH detected before 25 weeks gestation, 12 pregnancies were terminated. There were 11 survivors among the 25 continuing pregnancies (44%). The overall survival of babies with CDH is very poor but, when a defect is identified by ultrasound before 25 weeks gestation, chromosome analysis and a careful ultrasound scan may suggest which fetuses have an isolated diaphragmatic abnormality and a greater chance of survival.

Abnormalities, Multiple↗
PubMed1999

Left-isomerism sequence and maternal type-1 diabetes.

Defects of lateralisation have previously been recognised in the offspring of women with type-1 diabetes. In a 3-year period, three of the six cases of left isomerism sequence notified to the Northern Region Congenital Abnormality Survey were the infants of diabetic mothers. This finding suggests a specific association between bilateral left-sidedness and maternal type-1 diabetes.

Abnormalities, Multiple↗
PubMed1999

Immunization with a LEAPS heteroconjugate containing a CTL epitope and a peptide from beta-2-microglobulin elicits a protective and DTH response to herpes simplex virus type 1.

A ligand epitope antigen presentation system (LEAPS) heteroconjugate vaccine containing a CTL epitope (H1) from the HSV-1 immediate early protein ICP27 (322-332) and a peptide sequence (J) from beta-2-microglobulin (35-50) elicited protection from intraperitoneal viral challenge and promoted DTH responses. The H1 peptide and other H1 containing heteroconjugates did not elicit protection or DTH responses. Antibody to the H1 peptide could not be detected by ELISA following vaccination with peptide, heteroconjugate or natural infection. The LEAPS heteroconjugate appears to prime a Thl-like response which is subsequently boosted by infection. These studies show that attachment of the J peptide can make a CTL epitope into a vaccine which is immunogenic and promotes a protective Th1 type of response.

Amino Acid Sequence↗
PubMed1999

Congenital anterior abdominal wall defects in the north of England, 1986-1996: occurrence and outcome.

The aim was to describe trends in prevalence, maternal age-specific prevalence, associated anomalies, clinical outcomes and the sensitivity of antenatal diagnosis of congenital anterior abdominal wall defects (in particular gastroschisis and exomphalos). Data were identified from a population-based register of major congenital abnormalities in the Northern health region of England, the Northern Congenital Abnormality Survey (NorCAS), between 1986 and 1996. 296 cases were notified; there were 133 cases of gastroschisis, 98 exomphalos, 30 limb-body wall defects and 23 other anterior abdominal wall defects. 12 cases could not be classified. In 19 (6 per cent) the initial diagnosis was changed following case review. 30 (30.6 per cent) cases of exomphalos were associated with a chromosomal anomaly compared with 1 (0.8 per cent) case of gastroschisis. The total prevalence for the 11 years was 6.33 (95 per cent CI=5.57-7.08) per 10 000 live births, still births and terminations of pregnancy, and the overall birth prevalence was 4.30 (95 per cent CI=3.68-4.93) per 10 000 live births and still births. For gastroschisis, there was a significant increase over the study period in both the total prevalence (1.48 in 1986 to 5.29 per 10 000 in 1996; chi(2)=8.41, p=0.00433) and the birth prevalence (1.48 in 1986 to 4.72 per 10 000 in 1996; chi(2)=7.42, p=0.00644), but there was no such significant increase for exomphalos (total prevalence chi(2)=2.29, p=0.13055; birth prevalence chi(2)=0.16, p=0.69348). The maternal age-specific prevalence was highest in the 11-19 year age group for gastroschisis but in the 35-39 year age group for exomphalos. Fewer pregnancies with gastroschisis resulted in a termination and a greater proportion of cases were alive at one year compared with exomphalos. The sensitivity of abnormality detection by ultrasonography was 75 per cent and 77.3 per cent for gastroschisis and exomphalos, respectively. Antenatal diagnosis improved from 47.4 per cent during 1986-91 to 80 per cent between 1992-96 for gastroschisis (chi(2)=5.7, p=0.00169), and from 55.6 per cent to 68.8 per cent for isolated exomphalos, although this increase was not significant. Total and birth prevalence of gastroschisis increased in the Northern region between 1986 and 1996. For exomphalos, there was a trend towards an increase in total prevalence and towards a decrease in birth prevalence. This decreasing trend has been accompanied by improvements in antenatal detection and subsequent termination of cases of exomphalos associated with other anomalies.

Abdominal Muscles↗
PubMed1999

Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma.

In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.

Acute Disease↗
PubMed1999

Stent implantation reduces restenosis in patients with suboptimal results following coronary angioplasty.

BACKGROUND: Primary intracoronary stenting reduces the rate of restenosis when compared with balloon angioplasty (PTCA) in selected patients. The strategy of PTCA followed by provisional stent placement for suboptimal PTCA results may be preferable to universal stenting but has not yet been tested in a randomized trial. METHODS: An attempt was made to obtain an optimal result with PTCA alone in 143 patients. Stenting was required in 50 patients (35%) for significant coronary dissection or PTCA failure. In the remaining 93 patients, the angiographic result was assessed immediately using on-line quantitative coronary angiography and classified as either optimal (<15% residual stenosis) or suboptimal (>/=15% residual stenosis). Sixteen patients (11%) had an optimal result from PTCA. The remaining 77 (54%) patients had a suboptimal result and were immediately randomized either to no further treatment or to the placement of a stent. The primary end-point was the rate of restenosis (>50% stenosis), assessed by quantitative coronary angiography, at 6 months. RESULTS: Angiographic follow-up was completed in 132 patients. Restenosis occurred in 53 (36,69)% of patients with a suboptimal result randomized to PTCA alone compared with 24 (12,41)% of patients randomized to stent (P=0.023). There was no significant difference in minimal luminal diameter at follow-up between the randomized groups. The rate of restenosis was 14 (2,43)% in patients with an optimal PTCA result and 14 (5,28)% in those that required stenting. CONCLUSIONS: Optimal angiographic results following conventional PTCA are rare and the restenosis rate following suboptimal results is high. The strategy of stenting suboptimal results is associated with a significant reduction in the rate of stenosis.

Angioplasty, Balloon, Coronary↗
PubMed1999

Human primordial, primary and secondary ovarian follicles in long-term culture: effect of partial isolation.

Ovarian cortical tissue, donated by 20 women aged 25-43 years during gynaecological laparoscopies or laparotomies, was first cultured for 7-9 days as tissue slices, 0.1-0.3 mm in thickness, in extracellular matrix, to initiate the growth of the primordial and primary follicles. It was then divided into two parts, one of which was cultured further as slices, and the other one used for enzymatic (collagenase at 1, 0.5 or 0.25 mg/ml; 17 patients) or mechanical (four patients) partial isolation of the follicles. The tissue slices and the partially isolated follicles were cultured for a further 1-3 weeks in the matrix. After approximately 2 weeks in culture, some oocytes began to extrude from the follicles, which were usually at the secondary stage. They were small, 20-80 micrometer in diameter, and had a thin or absent zona. Polar bodies and meiotic chromosomes could be seen in these naked oocytes. This premature extrusion probably resulted from sub-optimal culture conditions. It occurred sooner in follicles that had been partially isolated using collagenase. Histologically, larger numbers of oocytes were observed in non-isolated slice cultures than in the partially isolated cultures. Initiation of growth of the follicles occurred during the first 7-9 days in culture within slices. In non-isolated slices and following mechanical partial isolation there were significantly more secondary follicles after 11-18 days in culture than following isolation with collagenase. The proportion of atretic follicles increased during all cultures, and it was significantly higher after partial isolation. Because partial isolation did not improve the survival or development of the follicles the optimal method for human ovarian follicles could be to culture them non-isolated within small tissue slices.

Adult↗
PubMed1999

Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways.

BACKGROUND: 10% of sporadic colorectal cancers are characterised by a low level of microsatellite instability (MSI-L). These are not thought to differ substantially from microsatelite-stable (MSS) cancers, but MSI-L and MSS cancers are distinguished clinicopathologically and in their spectrum of genetic alterations from cancers showing high level microsatellite instability (MSI-H). AIMS: To study the distribution of molecular alterations in a series of colorectal cancers stratified by DNA microsatellite instability. METHODS: A subset of an unselected series of colorectal cancers was grouped by the finding of DNA MSI at 0 loci (MSS) (n = 51), 1-2 loci (MSI-L) (n = 38) and 3-6 loci (MSI-H) (n = 25). The frequency of K-ras mutation, loss of heterozygosity (LOH) at 5q, 17p and 18q, and patterns of p53 and beta catenin immunohistochemistry was determined in the three groups. RESULTS: MSI-H cancers had a low frequency of K-ras mutation (7%), LOH on chromosomes 5q (0%), 17p (0%) and 18q (12.5%), and a normal pattern of immunostaining for p53 and beta catenin. MSI-L cancers differed from MSS cancers in terms of a higher frequency of K-ras mutation (54% v 27%) (p = 0.01) and lower frequency of 5q LOH (23% v 48%) (p = 0.047). Whereas aberrant beta catenin expression and 5q LOH were concordant (both present or both absent) in 57% of MSS cancers, concordance was observed in only 20% of MSI-L cancers (p = 0.01). CONCLUSIONS: MSI-L colorectal cancers are distinct from both MSI-H and MSS cancers. This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp.

Adenoma↗