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Biomedical subjects

C Walsh

Publications and source records attributed to C Walsh.

At least 73 records · Page 4Linked to original sources
PubMed1998

Cancer of the colon, rectum, and anus during pregnancy. The surgeon's perspective.

Colorectal carcinoma presenting during pregnancy is uncommon. Most patients present late in pregnancy, and greater than 80% have rectal tumors. Pregnant patients with unexplained rectal bleeding should be evaluated by anorectal examination and flexible sigmoidoscopy. Treatment is individualized to each patient, but a strategy of proceeding immediately with a surgical resection when a diagnosis is made early in pregnancy and allowing the fetus to develop to safe delivery before treating when the diagnosis is made late in pregnancy is recommended. Most patients present with advanced tumors and have a poor prognosis, but prognosis by stage is not different from that in the general population. Adjuvant radiation and chemotherapy have limited roles in the treatment of pregnant women with colon and rectal carcinoma. Future challenges are aimed at improving survival through earlier diagnosis and the development of adjuvant therapies that are effective in patients with advanced disease.

Anus Neoplasms↗
PubMed1998

Altitude training at 2690m does not increase total haemoglobin mass or sea level VO2max in world champion track cyclists.

Haemoglobin mass (Hb mass), maximum oxygen consumption (VO2max), simulated 4000 m individual pursuit cycling performance (IP4000), and haematological markers of red blood cell (RBC) turnover were measured in 8 male cyclists before and after (A) 31 d of altitude training at 2690 m. The dependent variables were measured serially after altitude on d A3-4, A8-9 and A20-21. There was no significant change in Hb mass over the course of the study and VO2max at d A9 was significantly lower than the baseline value (79.3 +/- 0.7 versus 81.4 +/- 0.6 ml x kg(-1) x min(-1), respectively). No increase in Hb mass or VO2max was probably due to initial values being close to the natural physiological limit with little scope for further change. When the IP4000 was analysed as a function of the best score on any of the three test days after altitude training there was a 4% improvement that was not reflected in a corresponding change in VO2max or Hb mass. RBC creatine concentration was significantly reduced after altitude training, suggesting a decrease in the average age of the RBC population. However, measurement of reticulocyte number and serum concentrations of erythropoietin, haptoglobin and bilirubin before and after altitude provided no evidence of increased RBC turnover. The data suggest that for these elite cyclists any benefit of altitude training was not from changes in VO2max or Hb mass, although this does not exclude the possibility of improved anaerobic capacity.

Adult↗
PubMed1998

Nursing assessments in New Zealand mental health.

During 1992 a new Mental Health Act was implemented in New Zealand. The Act created a new role, that of the duly authorised officer (DAO) which has been mainly carried out by community mental health nurses. During 1994 a multisite qualitative research study was undertaken to describe the newly structured mental health nursing role and examine the issues related to it. A key issue which emerged was the concern that the nursing role had been defined and resourced by other groups (legal, medical and management) on the basis of its visible tasks rather than the invisible components of professional nursing knowledge and expertise. The legal descriptions of the DAO role negated the highly developed assessment skills of mental health nurses, suggesting that nurses are there for advice and assistance. Yet expert clinical judgement was pivotal to the effective functioning of the new role. This paper argues that the initial nursing mental health crisis assessment which is carried out in the community is a highly skilled nursing activity which must be recognized and resourced accordingly.

Community Mental Health Services↗
PubMed1998

Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.

Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cyclooxygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial PO2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 10(8) organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury.

Animals↗
PubMed1998

A novel type of regulatory element is required for promoter-specific activity of the PDGF-B intronic enhancer region.

We have previously described a non-classical, promoter-specific enhancer for the human Platelet-Derived Growth Factor B (PDGF-B) gene. In JEG-3 choriocarcinoma cells the activity of the enhancer depends upon co-operation with a sequence (the Enhancer-Dependent cis Co-activator "EDC" element) within the promoter. The PDGF-B enhancer fails to activate heterologous promoters, indicating that promoter-specificity depends on an element within the enhancer that can recognise a target sequence within the promoter. Here we identify a sequence within the enhancer of the PDGF-B gene which directs activation of the PDGF-B promoter by distal cis-acting elements. This specifies the wild-type PDGF-B promoter as the target for the enhancer and has been designated the EDC specificity element (EDCse). The cell-type specific nature of this interaction is extended by the observation that the EDCse is also dispensable for enhancer activity in breast-cancer cells (ZR-75). Concomitant to this observation, JEG-3 and ZR-75 cells differ in the binding of nuclear factors to the EDCse. We discuss the relevance of the EDC/EDCse system in regulation of gene expression.

5' Untranslated Regions↗
PubMed1997

Left ventricular volume reduction surgery.

Left ventricular volume reduction has recently been introduced as a surgical treatment for end stage dilated cardiomyopathy. This operation involves the resection of a slice of viable left ventricular myocardium in order to reduce the wall tension imposed upon the contracting heart chamber. Early results are encouraging, but clinical evaluation on a larger scale is required. In the present article, we describe the indications, surgical principles and results of left ventricular volume reduction surgery with reference to our group's experience.

Animals↗
PubMed1997

P2 receptor excitation of rodent hypoglossal motoneuron activity in vitro and in vivo: a molecular physiological analysis.

The role of P2 receptors in controlling hypoglossal motoneuron (XII MN) output was examined (1) electrophysiologically, via application of ATP to the hypoglossal nucleus of rhythmically active mouse medullary slices and anesthetized adult rats; (2) immunohistochemically, using an antiserum against the P2X2 receptor subunit; and (3) using PCR to identify expression of P2X2 receptor subunits in micropunches of tissue taken from the XII motor nucleus. Application of ATP to the hypoglossal nucleus of mouse medullary slices and anesthetized rats produced a suramin-sensitive excitation of hypoglossal nerve activity. Additional in vitro effects included potentiation of inspiratory hypoglossal nerve output via a suramin- and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS)-sensitive mechanism, XII MN depolarization via activation of a suramin-sensitive inward current, decreased neuronal input resistance, and a slow-onset theophylline-sensitive reduction of inspiratory output likely resulting from hydrolysis of extracellular ATP to adenosine and activation of P1 receptors. Immunohistochemically, P2X2 receptors were detected in inspiratory XII MNs that were labeled with Lucifer yellow. These data, combined with identification of mRNA for three P2X2 receptor subunit isoforms within the hypoglossal nucleus (two of which have not been localized previously in brain) and the previous demonstration that P2X receptors are ubiquitously expressed in cranial and spinal motoneuron pools, support not only a role of P2 receptors in modulating inspiratory hypoglossal activity but a general role of P2 receptors in modulating motor outflow from the CNS.

Adenosine↗
PubMed1997

Developmental modulation of glutamatergic inspiratory drive to hypoglossal motoneurons.

Proper function of hypoglossal motoneurons (XII MNs) innervating tongue muscles is critical for respiratory control of the airway. Morphological and electrophysiological properties of XII MNs change during postnatal development, as do modulatory systems. Despite these changes, the system producing respiratory movements must remain fully functional throughout life. Modulatory systems have therefore received considerable attention since coordination of their development with a developing neuromuscular system may be critical for maintenance of continuous, efficient breathing. Developmental modulation of XII inspiratory activity by three transmitter systems is examined. Thyrotropin-releasing hormone (TRH) mediates an increase in MN input resistance (RN) in juvenile but not neonate MNs, and this likely underlies the developmental increase in TRH potentiation of inspiratory activity. Norepinephrine (NE) potentiation of inspiratory activity, which in the neonate is produced in part by an alpha 1-mediated increase in RN, also increases postnatally. Effects of purinergic transmission on XII inspiratory activity remain constant during the first 2 weeks of postnatal development. Adenosine-triphosphate (ATP) produces tonic excitation and inspiratory potentiation that likely result from activation of postsynaptic P2 receptors. A secondary inhibitory effect likely results from hydrolysis of ATP to adenosine and activation of presynaptic A1 adenosine receptors. The functional relevance of these postnatal changes is discussed.

Adenosine Triphosphate↗
PubMed1997

The IPL gene on chromosome 11p15.5 is imprinted in humans and mice and is similar to TDAG51, implicated in Fas expression and apoptosis.

We searched for novel imprinted genes in a region of human chromosome 11p15.5, which contains several known imprinted genes. Here we describe the cloning and characterization of the IPL ( I mprinted in P lacenta and L iver) gene, which shows tissue-specific expression and functional imprinting, with the maternal allele active and the paternal allele relatively inactive, in many human and mouse tissues. Human IPL is highly expressed in placenta and shows low but detectable expression in fetal and adult liver and lung. Mouse Ipl maps to the region of chromosome 7 which is syntenic with human 11p15.5 and this gene is expressed in placenta and at higher levels in extraembryonic membranes (yolk sac), fetal liver and adult kidney. Mouse and human IPL show sequence similarity to TDAG51 , a gene which was shown to be essential for Fas expression and susceptibility to apoptosis in a T lymphocyte cell line. Like several other imprinted genes, mouse and human IPL genes are small and contain small introns. These data expand the repertoire of known imprinted genes and will be helpful in testing the mechanism of genomic imprinting and the role of imprinted genes in growth regulation.

Amino Acid Sequence↗
PubMed1996

Chronic arterial responses to stent implantation: a serial intravascular ultrasound analysis of Palmaz-Schatz stents in native coronary arteries.

OBJECTIVES: We used intravascular ultrasound (IVUS) imaging to evaluate the chronic vessel responses to Palmaz-Schatz stents. BACKGROUND: Palmaz-Schatz stents have been shown to inhibit early elastic recoil and late arterial remodeling while triggering neointimal hyperplasia. However, changes occurring in native vessels surrounding stent struts have not been well studied. METHODS: Postintervention and follow-up (mean [+/-SD] 5.4 +/- 3.8 months) serial IVUS imaging was performed in 25 stents without restenosis and 24 with in-stent restenosis. Intravascular ultrasound imaging using automatic transducer pullback at 0.5 mm/s allowed measurement at 1-mm axial increments of external elastic membrane (EEM), stent and lumen cross-sectional areas (CSAs) and calculation of peristent plaque plus media (P + M = EEM - stent) CSA, intrastent plaque (stent-lumen) CSA, arterial remodeling (delta EEM CSA), tissue growth outside the stent (delta P + M CSA) and tissue growth within the stent (delta stent-lumen CSA). Volumes were calculated using the Simpson rule. RESULTS: Mean EEM CSA increased significantly from 16.9 +/- 5.0 mm2 after intervention to 18.4 +/- 4.9 mm2 at follow-up (p < 0.0001), reflecting an increase in P + M CSA surrounding the stent (1.6 +/- 1.3 mm2). Greater tissue growth within the stent (2.4 +/- 2.2 mm2) correlated weakly, but directly with tissue growth surrounding the stent (r = 0.356, p = 0.0121). The ratio of peristent/intrastent tissue growth correlated weakly with arterial remodeling (r = 0.282, p = 0.0525). Restenotic stents had more tissue growth both within and surrounding the stent than did nonrestenotic stents. Volumetric measurements, which could be obtained in 15 lesions, showed similar results. CONCLUSIONS: After implantation there is a chronic increase in plaque mass both within and surrounding the stents. The increase in peristent plaque mass is associated with adaptive remodeling.

Aged↗
PubMed1996

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.

Africa↗
PubMed1996

Analysis of thirteen trinucleotide repeat loci as candidate genes for schizophrenia and bipolar affective disorder.

A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affective disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases.

Base Sequence↗
PubMed1996

Evaluation of a HIV/AIDS education program for adolescents.

The adolescent population has recently been recognized as one of the groups at risk for human immunodeficiency virus (HIV) infection. Statistics are beginning to document the extent of this trend. This study is aimed at determining adolescent sexual behaviors and the efficacy of a medical student-run acquired immune deficiency syndrome (AIDS) education program. Medical students taught 2,169 high school students in the St. Louis area with a pre- and post- intervention questionnaire administered to record levels of HIV/AIDS knowledge and sexual practices. Data revealed that 56.4% of the respondents were sexually active with 70.4% having multiple partners and 61.0% admitting to unprotected sex. These students demonstrated a significant increase in their knowledge about HIV infection after the educational program. The results show that, adolescents are sexually active and more importantly, they are practicing behaviors that put them at risk for HIV/AIDS, a risk which they recognize. Finally, the educational intervention did increase students' knowledge of HIV/AIDS. This may not translate into a change in behaviors, but it is a first step.

Adolescent↗
PubMed1996

cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat.

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.

Amino Acid Sequence↗
PubMed1996

Genetic association between monoamine oxidase A microsatellite and RFLP alleles and bipolar affective disorder: analysis and meta-analysis.

The monoamine oxidase A locus (MAOA) at Xp11 was considered a good candidate to investigate in bipolar affective disorder since this enzyme plays an important role in the degradation of various neurotransmitters and a mutation in this gene has been associated with borderline mental retardation and a behavioural phenotype that has some resemblance to the manic syndrome. Previous association studies comparing allele frequencies of a microsatellite and RFLP at the monoamine oxidase A locus in bipolar affective disorder cases and controls in the UK have yielded conflicting results: Lim and colleagues reported a positive association, while no evidence for allelic association was obtained by Cradock and co-workers. A significant allelic association was observed between Japanese bipolar cases and controls at the MAOA microsatellite but different alleles seemed to be overrepresented in the bipolar cases in this population compared to the UK. In order to resolve these differences, we have examined this locus in our series of unrelated bipolar cases and age- and sex-matched controls and found significantly different MAOA microsatellite allele frequencies. In addition, we have pooled the data from the two previous UK studies with ours to create a total data set including 67 males and 113 females with bipolar affective disorder and a similar number of matched controls. No evidence for heterogeneity was observed for the control MAOA microsatellite or RFLP allele frequencies in these three studies. However, we found a significant difference between the pooled normal and bipolar allele frequencies both for the microsatellite and the RFLP at MAOA.

Alleles↗