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Biomedical subjects

M Rees

Publications and source records attributed to M Rees.

At least 19 recordsLinked to original sources
PubMed1997

Burial and seed survival in Brassica napus subsp. oleifera and Sinapis arvensis including a comparison of transgenic and non-transgenic lines of the crop.

The creation of transgenic plants through genetic engineering has focused interest on how the fitness of a plant species may be altered by small changes in its genome. This study concentrates on a key component of fitness: persistence of seeds overwinter. Seeds of three lines of oilseed rape (Brassica napus subsp. oleifera DC Metzger) and of charlock (Sinapis arvensis L.) were buried in nylon mesh bags at two depths in four habitats in each of three geographically separated sites: Cornwall, Berkshire and Sutherland. Seeds were recovered after 12 and 24 months. Charlock exhibited much greater seed survival (average 60% surviving the first year and 32.5% surviving the second year) than oilseed rape (1.5% surviving the first year and 0.2% surviving the second) at all sites. Charlock showed higher survival at 15 cm burial than 2 cm burial at certain sites, but oilseed rape showed no depth effect. Different genetic lines of oilseed rape displayed different rates of seed survival; non-transgenic rape showed greater survival (2%) than the two transgenic lines, one developed for tolerance to the antibiotic kanamycin (0.3%) and one for tolerance to both kanamycin and the herbicide glufosinate (0.25%). The absolute and relative performances of the different genetic lines of oilseed rape were context specific, illustrating the need to test hypotheses in a wide range of ecological settings.

Brassica↗
PubMed1997

Psychological effects of continuation versus discontinuation of hormone replacement therapy by estrogen implants: a placebo-controlled study.

There is conflicting evidence regarding the effects of hormone replacement therapy (HRT) with estrogens on psychological and psychiatric symptoms of menopause. Forty women already attending a menopause clinic for continuing HRT by estrogen implants were studied in a randomized, double-blind, placebo-controlled study of estrogen reimplantation versus implantation of a placebo preparation. Assessment included self rating with visual analog scales, standardized psychological and menopause rating scales (Hospital Anxiety and Depression Scale, Self-Concept Questionnaire, Cognitive Failures Questionnaire, Greene Menopause Index), and interview with the Present State Examination. No difference in outcome with regard to either psychological or psychiatric symptoms was found 2 months after entry to the study between the women who received an active implant and those who received a placebo implant, in spite of the former group having a significant rise in estradiol levels. The only effect of HRT on physical symptoms was a nonsignificant reduction in flushes. Psychiatric morbidity of the study population was high with nearly half being "psychiatric cases" according to the Present State Examination at both initial assessment and follow-up. At entry to the study nearly all the women had levels of estradiol in the premenopausal range and four had supraphysiological levels. It appears likely that women were returning requesting a new implant because of symptoms related to nonhormonal factors. Women receiving continuing HRT for menopausal symptoms should be reassessed both for hormonal status and current psychosocial factors when they present with recurrent symptoms, especially those of a psychological or psychiatric nature.

Adult↗
PubMed1997

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.

Chromosome Mapping↗
PubMed1997

The incidence of coronary artery calcification on standard thoracic CT scans.

Coronary artery calcification indicates the presence of atheromatous disease and can represent an area of severe stenosis. The absence of calcification does not correlate with the absence of coronary artery disease, but an incidental finding of calcification has important prognostic implications. The best method available at present is electron beam computed tomography (EBCT) but these are often dedicated units in specialist centres and currently this modality is not widely available in the UK. This is the first study to establish the age/sex frequency with which incidental coronary artery calcification is detected using standard CT scanning in a large population. The methods used are simple, reproducible and based on standard thoracic protocols. The presence of calcification is easily detected using readily available equipment. The reported incidence of calcification using EBCT, the most sensitive method available, was compared with standard CT detection rates. While standard CT underestimates the presence of calcification, the age/sex trends are very similar. Standard CT probably detects the most dense lesions, missing areas of mild calcification, recent studies having shown that these lesions are most likely to represent areas of stenosis. This study shows that, with very little change in current practice and on readily available equipment, it is possible to obtain important diagnostic information suggesting the presence of severe coronary artery disease.

Adult↗
PubMed1997

Linkage analysis between idiopathic generalized epilepsies and the GABA(A) receptor alpha5, beta3 and gamma3 subunit gene cluster on chromosome 15.

INTRODUCTION: We tested the hypothesis that genetic variants within the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster on chromosome 15q11-q13 confer genetic susceptibility to common subtypes of idiopathic generalized epilepsy (IGE). MATERIAL AND METHODS: Ninety-four families were selected from IGE patients with either juvenile myoclonic epilepsy (JME), juvenile (JAE) or childhood absence epilepsy (CAE). Cosegregation was tested between dinucleotide polymorphisms associated with the human GABA(A) alpha5, beta3 and gamma3 subunit gene cluster and three different IGE trait models. RESULTS: Evidence against linkage to the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster was found in the entire family set and subsets selected from either CAE or JAE. In 61 families of JME patients, a maximum lod score (Zmax=1.40 at Theta(max)=0.00) was obtained for a broad IGE spectrum ("idiopathic" generalized seizure or generalized spike and wave discharges in the electroencephalogram) assuming genetic heterogeneity (alpha=0.37; P=0.06) and an autosomal recessive mode of inheritance. CONCLUSION: The possible hint of linkage in families of JME patients emphasizes the need for further studies to determine whether a recessively inherited gene variant within the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster contributes to the pathogenesis of "idiopathic" generalized seizures and associated EEG abnormalities in a proportion of families.

Chromosomes, Human, Pair 15↗
PubMed1997

Late results justify resection for multiple hepatic metastases from colorectal cancer.

BACKGROUND: Whilst hepatic resection is accepted for single colorectal metastases, the role of surgery for multiple deposits is less certain. This study reports results of a programme of aggressive resection of hepatic metastases. METHODS: Of 150 hepatic resections for colorectal metastases, 107 patients have completed 1-9 years' follow-up for this actuarial survival analysis. Indications for resection were disease confined to the liver, resectability of all metastases and preservation of sufficient hepatic parenchyma. RESULTS: One patient (1 per cent) died after operation and six (6 per cent) suffered serious complications (two surgical and four medical) but with full recovery. Patients who had a radical resection (n = 89) had 1- and 5-year survival rates of 94 and 37 per cent respectively. A palliative group (n = 18) with disease elsewhere (n = 9) or positive histological margins (n = 9) had corresponding survival rates of 56 and 6 per cent. Univariate analysis of the group who had radical surgery demonstrated that survival depended on size of metastases (less than 7 cm) (P = 0.014), width of clear resection margin (greater than 5 mm) (P = 0.004) and primary site (P = 0.010). Factors not affecting outcome were number of metastases, unilateral versus bilateral disease, synchronous versus metachronous spread, tumour differentiation and Dukes stage. Multivariate analysis demonstrated independent survival advantage for small metastases (less than 7 cm) (P = 0.002) and clear resection margin greater than 5 mm (P = 0.037). CONCLUSION: Hepatic resection in selected patients with single and multiple colorectal hepatic metastases is justified.

Colorectal Neoplasms↗
PubMed1996

One hundred and fifty hepatic resections: evolution of technique towards bloodless surgery.

A technique of hepatic resection is described and the results of 150 resections are reviewed. Hepatic transection was performed, under intermittent portal inflow occlusion, using ultrasonic aspiration to skeletonize portal branches and venous tributaries. Control of venous haemorrhage during resection was optimized by argon beam coagulation and lowering central venous pressure to between 0 and 4 cmH2O by extradural blockade and systemic nitroglycerine infusion. One patient with jaundice died in hospital, giving a mortality rate of 0.7 per cent. There were no deaths in patients without jaundice and cirrhosis. Fifteen patients (10.0 per cent) had significant complications, nine medical and six surgical, including three bile leaks (2.0 per cent). Mean blood loss was 814 ml for the whole study but only 434 ml in the last 4 years. During this latter period mean blood transfusion in hospital was 0.5 units and mean postoperative haemoglobin value fell by 0.7 g per 100 ml. Hepatic resection can be performed with the same degree of confidence and similar low morbidity as any other major surgical procedure.

Adolescent↗
PubMed1996

Professional responses to innovation in clinical method: diabetes care and negotiating skills.

OBJECTIVE: To describe the responses of family doctors and nurses to applying an innovative clinical technique and technology in the context of a randomised controlled trial. DESIGN: Multi-faceted descriptive analysis of professional responses in the experimental arm of the trial. SUBJECTS AND SETTING: 29 family practices involving 30 doctors and 33 nurses over a 3-year time scale and 200 patients with type II diabetes. INTERVENTION: A new visual agenda-setting technology and other visual aids applied using the techniques of negotiation and motivational interviewing. OUTCOME MEASURES: Uptake of training, use of the method, group discussions, willingness to accept consultation recordings. RESULTS: 100% of clinicians welcomed two or more formal training sessions. The agenda-setting technology was used frequently by 71% of clinicians and occasionally by a further 22%. High levels of engagement with the method occurred among nurses but many doctors also reported benefits. CONCLUSIONS: Family doctors and nurses in Wales have found a new technology to facilitate negotiation in diabetes consultation acceptable and useful. Analysis of outcome is now awaited.

Attitude of Health Personnel↗
PubMed1996

Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis.

Hyperekplexia is a rare condition characterised by the presence of neonatal hypertonia and an exaggerated startle response. Mutations have been described in GLRA1, the gene encoding the alpha 1 subunit of the glycine receptor, in dominant families with hyperekplexia and in a single sporadic case, thought to represent an autosomal recessive form of the disease. In this study the coding region of the GLRA1 was analysed in eight probands with hyperekplexia by restriction digest and sequencing. Two familial cases were found to possess the previously described G1192A (R271Q) mutation in exon 6. In an additional family in which hyperekplexia cosegregates with spastic paraparesis, a novel A to G transversion at nucleotide 1206 in exon 6 was detected that changes a lysine at amino acid 276 to a glutamate (K276E). In four sporadic cases no mutations were found. In addition, one familial case did not have a mutation in the coding region of the gene.

Base Sequence↗
PubMed1996

Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region.

Linkage analysis in separately ascertained families of probands with juvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated "EJM1"), on chromosome 6p, predisposing to a trait defined as either clinical JME, its associated electroencephalographic abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed in 19 families in which a proband and at least one first- or two second-degree relatives have clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was carried out under the assumptions of autosomal dominant inheritance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region formally excluded (LOD score < -2) by using multipoint analysis varies depending on the assumptions made concerning inheritance parameters and the proportion of linked families, alpha-that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected individuals as unknown or excluding a subset of four families in which pyknoleptic absence seizures were present in one or more individuals did not alter these conclusions.

Adolescent↗
PubMed1995

Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor.

IL-2 therapy is a potent inductive stimulus for nitric oxide (NO.) synthesis in mice and humans. It is not yet clear whether NO. can contribute to IL-2-induced therapeutic responses. The murine skin cancer Meth A is relatively resistant to lymphokine-activated killer (LAK) cell killing, allowing evaluation of the role of IL-2-induced NO. synthesis in vivo, without contribution by LAK cells. Subcutaneous IL-2 treatment of mice bearing i.p. Meth A tumor increased nitrite production by cells derived from ascites (63 +/- 14 microM vs 3.2 +/- 1.5 microM in untreated controls). N omega-monomethyl-L-arginine (MLA), NO. synthase inhibitor, prevented this increase. NO. production correlated in an inverse fashion with tumor cell proliferation in vitro. Evidence for IL-2-induced heme nitrosylation was demonstrated in tumor cells by electron paramagnetic resonance spectroscopy. By immunomagnetic depletion experiments, macrophages were implicated as a major source of NO. synthesis. Cytologic and flow-cytometric evaluation revealed that IL-2 treatment resulted in enhanced lymphocyte and macrophage recruitment into malignant ascites, and decreases in tumor cell recovery. MLA administration further increased host cell recovery. Subcutaneous IL-2 therapy increased urinary nitrate excretion up to eightfold in mice, and appeared to produce a significant survival advantage that was prevented by MLA administration.

Animals↗
PubMed1995

No evidence for allelic association between bipolar disorder and monoamine oxidase A gene polymorphisms.

We have tested the hypothesis that DNA markers in the MAOA gene show allelic association with bipolar affective disorder. Eighty-four unrelated Caucasian patients with DSM III-R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8. No evidence for allelic association was observed between any of the markers and bipolar disorder.

Adult↗
PubMed1995

Computed tomographic portography in preoperative imaging of hepatic neoplasms.

Preoperative selection of suitable patients for liver resection is dependent on the quality of radiological imaging. Computed tomography (CT) identifies approximately 70 per cent of lesions. Computed tomographic arterial portography (CTAP) during contrast enhancement of the liver via the portal vein may be superior to conventional CT. Preoperative CTAP was evaluated in 60 patients with hepatic neoplasm (48 having colorectal metastases) who subsequently underwent laparotomy. The preoperative images were compared with intraoperative palpation, intraoperative ultrasonography and histology of the resected liver. Fifty-six patients (93 per cent) underwent partial hepatectomy. The detection rate sensitivity for CTAP was 110 of 116 lesions in the 56 patients (95 per cent) and for intraoperative ultrasonography was 114 of 116 (98 per cent). CTAP correctly identified all lesions found at histology in 50 of 56 (89 per cent) resected specimens. At laparotomy four of 60 patients (7 per cent) were inoperable; two of these had been predicted to be so by this technique. CTAP correctly identifies and locates the majority of hepatic tumours, particularly metastases, and is the procedure of choice for selection of suitable candidates for partial hepatectomy.

Adult↗