Early neurological deterioration in acute stroke.
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Brain Damage, Chronic↗
Biomedical subjects
F Wright
Publications and source records attributed to F Wright.
Update on nandrolone and norsteroids: how endogenous or xenobiotic are these substances?
Norsteroids are xenobiotics with androgenic and anabolic properties known since as far back as the 1930s. In doping controls, the use of the banned xenobiotic norsteroids is detected in the competitor's urines by the measurement of norandrosterone (19-NA) and noretiocholanolone (19-NE), which are the main metabolites for nandrolone (NT) and most norsteroids with anabolic properties. In 1996, the IOC subcommission "Doping and Biochemistry of Sport" informed the Heads of the "IOC Accredited Laboratories" that the recommended cut-off limit for reporting an offence was to be 1-2 ng ml(-1) urine for either 19-NA or 19-NE. We will discuss how technical progress in gas chromatography coupled to high-resolution mass spectrometry permitted a dramatic increase in sensitivity with a detection limit of 1 pg ml(-1) urine, or less, and an assay limit of 20-50 pg ml(-1) urine, for either 19-NA or 19-NE. As a paradox, norsteroids have been known for decades as not only xenobiotics but also obligatory endogenous intermediates in the biosynthesis of estrogens from androgens in all species, man included. It is this biochemical observation which fed the active scientific and medical controversy initiated in 1998 over the possibly endogenous production of nandrolone and metabolites well over the new IOC's recommended cut-off limit of 2 ng ml(-1) urine. Notwithstanding the particular technical difficulties attached, we will provide data and discuss the minute endogenous levels detected and measured in man either at rest, after performance or training and compare them to the relatively high levels reported in male athlete's doping controls today. We will also discuss data on the pharmacological effects of some contraceptive therapies containing norsteroids in women. In view of the well-documented noxious effects repeatedly observed after anabolic steroid misuse, the confirmation and implementation of technically proven procedures for reporting norsteroid abuse in sports seems an important enough goal to protect athlete's health against such abuses and justifies up dating the review of the patent scientific and medical experience and knowledge gained over the last 50 years on nandrolone and its minor production in man and woman.
Chromatography, High Pressure Liquid↗
Somatoform dissociation in eating-disordered patients.
This study investigated the role of somatoform dissociation in eating disorders and pathological eating behaviour, relative to the established association of eating pathology with psychological dissociation. The participants were 131 women with DSM-IV diagnoses of anorexic or bulimic disorders and 75 women who had no such disorder. Each woman completed measures of psychological and somatoform dissociation, as well as a measure of bulimic attitudes. The current presence or absence of specific bulimic behaviours was identified during the clinical interview. Levels of both forms of dissociation were higher in the women who had diagnoses of disorders with a bulimic component (bulimia nervosa; anorexia nervosa of the binge/purge subtype) than in the non-clinical or restrictive anorexic women. Somatoform dissociation showed particularly strong links with the presence of bulimic behavioural features (excessive exercise, laxative abuse, diet pill abuse, diuretic abuse) and with bulimic attitudes. The formulation and treatment of cases where there are bulimic features is likely to be enhanced by the assessment of somatoform dissociation.
Adult↗
Urinary profile of androgen metabolites in a population of sportswomen during the menstrual cycle.
The aim of this investigation was to evaluate the urinary profile of androgen metabolites during menstrual cycle in both young-trained female athletes, and young sedentary women, not presenting any pathological signs. Urines were collected for 24 hours (08 : 00 a. m. the first day to 08 : 00 a. m. the second day) from all sportive and sedentary subjects. All steroids were measured by specific radioimmunological analysis, and the implications of these results in terms of concentrations and modifications by exercise will be discussed. During follicular phase, control values were respectively, testosterone glucuronide (TG): 1.67 +/- 0.70 nmol x mmol C -1; epitestosterone glucuronide (ETG): 2.51 +/- 0.88 nmol x mmol C -1; TG/ETG ratio: 0.72 +/- 0.26 and cortisol (FLU): 10.02 +/- 0.79 nmol x mmol C -1. No significant modifications were observed during luteal phase (respectively: TG: 1.48 +/- 0.50 nmol x mmol C -1; ETG: 2.65 +/- 0.93 nmol x mmol C -1; TG/ETG ratio: 0.67 +/- 0.31 and FLU: 9.29 +/- 3.37 nmol x mmol C -1. Similarly, no significant effect of physical training was observed on studied parameters between these two groups during either follicular phase (TG: 1.96 +/- 1.00 nmol x mmol C -1; ETG: 1.97 +/- 0.70 nmol x mmol C -1; TG/ETG ratio: 0.66 +/- 0.05 and FLU: 11.31 +/- 3.73 nmol x mmol C -1) or luteal phase (TG: 1.93 +/- 0.86 nmol x mmol C -1; ETG: 3.19 +/- 1.23 nmol x mmol C -1; TG/ETG ratio: 0.69 +/- 0.33 and FLU: 9.52 +/- 3.86 nmol x mmol C -1). It is concluded that although physical training could play a role in androgen metabolism, it has no significant incidence on urinary TG/ETG ratio. This study thus confirms that sportswomen can also be considered as normal subjects when they do not present any obvious endocrine disorder induced by physical activity.
Adult↗
Outbreaks of infectious disease associated with private drinking water supplies in England and Wales 1970-2000.
In England and Wales over the last 30 years there have been 25 reported outbreaks of infection, associated with private water supplies (PWS). The majority (16 outbreaks) were reported after the introduction of enhanced surveillance. Although PWS only serve 0.5% of the population, 36% of drinking water outbreaks are associated with PWS. The main pathogen, campylobacter, was implicated in 13 (52%) outbreaks. Most reported outbreaks (88%) occurred in commercial or Category Two supplies, which potentially affect larger populations. The main factors implicated in these outbreaks are temporary or transient populations, treatment (lack or failure), the presence of animals and heavy rains. The public health problem associated with PWS could be prevented by the identification and understanding of risk factors, by the proper protection of water sources and adequate treatment and maintenance. This could be facilitated through the introduction of a risk assessment as part of a scheme for PWS.
Communicable Disease Control↗
Copy-DNA cloning and characterisation of a potato alpha-glucosidase: expression in Escherichia coli and effects of down-regulation in transgenic potato.
Polymerase chain reaction-based methodology was used to obtain a cDNA clone (MAL2) from potato (Solanum tuberosum L.) with the sequence characteristics of an alpha-glucosidase. Phylogenetic analysis of the deduced polypeptide encoded by this cDNA demonstrated that the most similar sequences were alpha-glucosidases and alpha-xylosidases of plant origin. The MAL2 cDNA was expressed in Escherichia coli and the recombinant MAL2 protein was affinity-purified. MAL2 catalysed the hydrolysis of a range of maltooligomers and p-nitrophenyl-alpha-D-glucopyranoside with a pH optimum of 5.5-5.7. The substrate with the lowest Km value was maltotetraose (3.7 mM). The MAL2 expression product did not catalyse the hydrolysis of xyloglucan oligosaccharides, p-nitrophenyl-alpha-D-xylopyranoside or gelatinised potato starch. MAL2 was down-regulated in transgenic potato plants using an antisense approach. In several independent transgenic antisense lines, MAL2 expression was severely down-regulated. Despite this, no decrease in total extractable alpha-glucosidase and alpha-xylosidase activity could be detected in tissues from the transgenic plants. In glasshouse trials, no visible phenotype, change in tuber yield or carbohydrate content was associated with MAL2 down-regulation. The implications of these results are discussed.
Cloning, Molecular↗
Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARalpha fusion gene formation, relapsing as acute promyelocytic leukaemia M3.
Demonstration of either the translocation t(15;17)(q22;q21) or the fusion of PML and RARalpha genes is regarded as diagnostic for acute myeloid leukaemia (AML) of FAB type M3, but has occasionally been seen in other FAB types. We present two such cases. Case 1 presented with FAB type M6 and a complex karyotype involving chromosomes 1, 2, 11 and 17. Bone marrow relapse of FAB type M3 followed autologous bone marrow transplantation. Subsequent marrow dysplasia and an M6 relapse were accompanied by a new cytogenetic clone involving chromosomes X, 2, 4, 6, 7 and 16. Fluorescence in situ hybridization (FISH) of metaphase chromosomes at diagnosis showed insertion of material from chromosome 17 into a 'normal' 15 with juxtaposition of PML and RARalpha. Case 2 presented as AML M4 and relapsed as M3. Cytogenetic analysis at diagnosis and in relapse showed 46,XY,t(15;17)(q22;q11),del(16)(q22). FISH analysis showed this to be a three-way translocation involving chromosomes 15, 16 and 17 again with juxtaposition of PML and RARalpha. Reverse transcription-polymerase chain reaction (RT-PCR) revealed PML/RARalpha fusion at diagnosis, in remission and in first relapse. These examples strengthen the case for RT-PCR screening of all AML patients for these fusion genes.
Adult↗
Detection of recombination in DNA multiple alignments with hidden Markov models.
Conventional phylogenetic tree estimation methods assume that all sites in a DNA multiple alignment have the same evolutionary history. This assumption is violated in data sets from certain bacteria and viruses due to recombination, a process that leads to the creation of mosaic sequences from different strains and, if undetected, causes systematic errors in phylogenetic tree estimation. In the current work, a hidden Markov model (HMM) is employed to detect recombination events in multiple alignments of DNA sequences. The emission probabilities in a given state are determined by the branching order (topology) and the branch lengths of the respective phylogenetic tree, while the transition probabilities depend on the global recombination probability. The present study improves on an earlier heuristic parameter optimization scheme and shows how the branch lengths and the recombination probability can be optimized in a maximum likelihood sense by applying the expectation maximization (EM) algorithm. The novel algorithm is tested on a synthetic benchmark problem and is found to clearly outperform the earlier heuristic approach. The paper concludes with an application of this scheme to a DNA sequence alignment of the argF gene from four Neisseria strains, where a likely recombination event is clearly detected.
Algorithms↗
Probabilistic divergence measures for detecting interspecies recombination.
This paper proposes a graphical method for detecting interspecies recombination in multiple alignments of DNA sequences. A fixed-size window is moved along a given DNA sequence alignment. For every position, the marginal posterior probability over tree topologies is determined by means of a Markov chain Monte Carlo simulation. Two probabilistic divergence measures are plotted along the alignment, and are used to identify recombinant regions. The method is compared with established detection methods on a set of synthetic benchmark sequences and two real-world DNA sequence alignments.
Computational Biology↗
Introduction to the special section on contemporary theoretical developments and the implications for group psychotherapy.
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Humans↗
Genomic structure of the gene for the human P1 protein (MCM3) and its exclusion as a candidate for autosomal recessive polycystic kidney disease.
The locus PKHD1 (polycystic kidney and hepatic disease 1) has been linked to all typical forms of the autosomal recessive polycystic kidney disease (ARPKD) and maps to chromosome 6p21.1-p12. We previously defined its genetic interval by the flanking markers D6S1714 and D6S1024. In our current work, we have fine-mapped the gene for the human P1 protein (MCM3), thought to be involved in the DNA replication process, to this critical region. We have also established its genomic structure. Mutation analyses using SSCP were performed in ARPKD patients' cDNA samples, leading to the exclusion of this gene as a candidate for this disorder. We also identified two intragenic polymorphisms that allowed families with critical recombination events to be evaluated. Although neither marker was informative in these individuals, they are the closest yet described for PKHD1 and may help to refine the candidate region.
Cell Cycle Proteins↗
A potato alpha-glucosidase gene encodes a glycoprotein-processing alpha-glucosidase II-like activity. Demonstration of enzyme activity and effects of down-regulation in transgenic plants.
In order to elucidate more fully the function of a potato gene (MAL1) encoding alpha-glucosidase activity, transgenic plants in which MAL1 expression was down-regulated were generated using antisense technology. In transgenic lines severely down-regulated in the expression of MAL1, total alpha-glucosidase activity was not decreased in leaves and tubers, and the contents of starch, glucose, fructose and sucrose remained unchanged in tubers. Phylogenetic analysis indicated that the MAL1 gene product was more similar to the glycoprotein-processing alpha-glucosidase II of mammalian and yeast origin than to other plant alpha-glucosidases. Using [14C-Glc]-labelled Glc2Man9GlcNAc2 as a substrate, it was demonstrated that glucosidase II activity was markedly down-regulated in microsomes isolated from tubers of four independent antisense lines studied in detail, strongly suggesting that MAL1 encodes glucosidase II activity. In field trials (but not in the glasshouse), MAL1 down-regulation produced an extremely stunted phenotype - the leaves were curled and tuber yield was decreased by 90% compared to control values. Microscopic analysis of leaves revealed significant differences between the antisense and control samples. Plants with down-regulated glucosidase II activity showed a greater degree of plasmolysis, and an increase in the size of mesophyll intracellular spaces. Analysis of cell walls also indicated changes in structure as a result of MAL1 down-regulation. In leaves from four antisense lines, the steady-state transcript level corresponding to the endoplasmic reticulum chaperone, BiP, was enhanced. This is diagnostic of stress in the endoplasmic reticulum.
Carbohydrate Metabolism↗
Radiation-induced esophageal squamous cell carcinoma in situ.
A report of radiation-induced squamous cell carcinoma in situ of the esophagus is presented. This report indicates that the patient developed the carcinoma in situ many years after chest wall irradiation for breast cancer treatment. A review of the literature with respect to carcinogenesis after radiotherapy is included and recommendations for the follow-up of patients having mediastinal radiation are suggested.
Aged↗
Introduction to the special section on contemporary relational psychologies and group therapy.
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Humans↗
The use of the self in group leadership: a relational perspective.
This article, written from a relational perspective, describes a shift that is taking place in the thinking of many psychodynamically oriented psychotherapists regarding the practice of therapy and the implications it has for group therapists. The shift, from one-person to two-person and multi-person theory, has particular importance for group leaders since it recommends making the subjective involvement of the therapist in the interactional field of the group much more a part of the treatment process. Theory and research on the use of countertransference, non-interpretive interventions, humor, and spontaneity by the leader are reviewed and vignettes are presented to illustrate the application of these ideas. Guidelines regarding the application of such ideas in group therapy are also discussed.
Countertransference↗
TOPAL 2.0: improved detection of mosaic sequences within multiple alignments.
MOTIVATION: The Dss statistic was proposed by McGuire et al. (Mol. Biol. Evol., 14, 1125-1131, 1997) for scanning data sets for the presence of recombination, an important step in some phylogenetic analyses. The statistic, however, could not distinguish well between among-site rate variation and recombination, and had no statistical test for significant values. This paper addresses these shortfalls. RESULTS: A modification to the Dss statistic is proposed which accounts for rate variation to a large extent. A statistical test, based on parametric bootstrapping, is also suggested. AVAILABILITY: The TOPAL package (version 2) may be accessed from http:/ /www.bioss.sari.ac.uk/frank/Genetics and by anonymous ftp from typ://ftp.bioss.sari.ac.uk in the directory pub/phylogeny/topal. CONTACT: frank@bioss.sari.ac.uk
Algorithms↗
Esophageal dilation in patients with previous esophageal perforation.
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Catheterization↗
Laparoscopic colon resections: a five-year retrospective review.
In recent years, laparoscopic surgery has become a matter of growing interest. It has been shown that laparoscopic colectomy is well tolerated and safe for benign disease. However, there is some uncertainty about using this method for malignant disease when curative resection is the aim. These uncertainties mainly consist of spread of cancer to port site, long-term survival, and adequacy of resection. The majority of laparoscopic colectomies are technically assisted procedures in which anastomosis is performed outside the abdomen. However, some surgeons are now performing this surgery totally laparoscopically with the anastomosis performed inside the abdomen. Laparoscopic colectomy is currently practiced with great frequency by general surgeons. Its performance requires a steep learning curve and a large number of cases to obtain proficiency. The indications for laparoscopic colectomy are different from one institution to another. In some institutions all patients with colorectal disease are candidates for laparoscopic colectomy and in others it may be limited to benign disease only. The purpose of this review is to analyze all laparoscopic colectomies performed at our medical center since 1992. We conducted a retrospective chart review of both hospital and clinic charts of patients who underwent colectomies at our hospital. A total of 338 patient charts were reviewed. In a comparison of both laparoscopic (n = 285) and converted (n = 53) methods, the age and operative time were about the same. Age average and operating room time average were similar for both groups. With laparoscopy, there was a 3-day drop in length of hospital stay as well as a 1-day-earlier regaining of bowel function. Hospital cost dropped 5000 dollars average for the laparoscopic colectomy. The conversion rate at our center was 15 per cent. Complication rates were lower in the laparoscopic group. Recurrence of cancer at the port site (0.7%) was no higher than in the converted group (incisional recurrence, 1.8%). We conclude that laparoscopic colectomy does show an improvement in return of bowel function, hospital cost, and shorter hospital stay. Long-term follow-up will be necessary to determine the effectiveness of laparoscopic colon resection for colorectal cancer.
Age Factors↗