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Biomedical subjects

T Walsh

Publications and source records attributed to T Walsh.

At least 19 recordsLinked to original sources

Is vaginal breech delivery outdated for all singletons and twins? The current kaleidoscope of obstetric thinking.

The best practice for the delivery of a term breech in singleton and twin pregnancies is still controversial. We sought the opinions of obstetricians working in Ireland. A questionnaire was used to address the management of the obstetrician's "own hypothetical pregnancy" in three different scenarios. We also inquired about factors which might influence the decision on mode of delivery. The response rate was 104/174 (60%). In the scenario of a singleton fetus presenting by the breech in a nulliparous woman, 15/84 (18%) of obstetricians would chose a spontaneous vaginal delivery compared to 40/80 (50%) for a multiparous woman (p < 0.01). In the scenario of a second twin in breech presentation (nulliparous and multiparous), 75/93 (81%) would choose a spontaneous vaginal delivery. When asked about a singleton cephalic presentation, 85/91 (93%) would choose a spontaneous vaginal delivery. These decisions were influenced by concerns about perinatal morbidity [91/100 (91%)], published evidence [73/98 (75%)], the delivery doctor's inexperience [56/94 (60%)], but not by gender. Our study indicates that obstetricians in Ireland consider that there is a role for vaginal breech delivery in selected scenarios.

Attitude of Health Personnel↗

Smoking and alcohol in pregnancy. Survey in the immediate post-partum period.

This was a questionnaire-based study of 151 postnatal women. We found 42% of women were smokers prior to pregnancy and only 37% of these women succeeded in quitting smoking during pregnancy. Success in quitting was significantly related to the number of cigarettes smoked (p<0.05). However, 71% of pregnant smokers were aware of the associated risks. Alcohol was consumed by 89% of women and 10% admitted to binge drinking during pregnancy. Only 44% of the study group were aware of the associated risks of alcohol. We propose that we need to change our social acceptance of these behaviours before pregnancy, and provide support to those women during pregnancy.

Adolescent↗

Quality control and reference guidelines for CLSI broth microdilution susceptibility method (M 38-A document) for amphotericin B, itraconazole, posaconazole, and voriconazole.

Although standard conditions are available for testing the susceptibilities of filamentous fungi to antifungal agents by the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards) broth microdilution assay, quality control (QC) MIC limits have not been established for any mold-agent combination. This multicenter (eight-center) study documented the reproducibility of tests for one isolate of Paecilomyces variotii ATCC MYA-3630 and 11 other mold isolates (three isolates of Aspergillus fumigatus; two isolates of A. terreus; one isolate each of A. flavus, A. nidulans, Fusarium moniliforme, and F. solani; and two isolates of Scedosporium apiospermum) by the CLSI reference broth microdilution method (M 38-A document). Control limits (amphotericin B, 1 to 4 microg/ml; itraconazole, 0.06 to 0.5 microg/ml; posaconazole, 0.03 to 0.25 microg/ml; voriconazole, 0.015 to 0.12 microg/ml) for the selected QC P. variotii ATCC MYA-3630 were established by the analysis of replicate MIC results. Reference isolates and corresponding MIC ranges were also established for 6 of the 12 molds evaluated. MIC limits were not proposed for the other five molds tested due to low testing reproducibility for these isolates.

Amphotericin B↗

Granisetron vs ondansetron for prevention of nausea and vomiting in hematopoietic stem cell transplant patients: results of a prospective, double-blind, randomized trial.

The serotonin type-3 (5-HT3) antagonists represent a significant advance in the prevention of acute nausea and vomiting (N/V) from highly emetogenic chemotherapy. We sought to determine if any differences in efficacy or adverse effects exist between two such agents, ondansetron and granisetron, during conditioning therapy for hematopoietic stem cell transplantation (HSCT). Patients were randomized to receive either ondansetron 0.15 mg/kg intravenously every 8 h or granisetron 10 microg/kg intravenously daily. Additionally, all patients received scheduled dexamethasone and lorazepam. Prophylaxis was continued until 24 h after completion of chemotherapy. Nausea and distress were measured subjectively with visual analog scales and emetic episodes were quantified. Of the 110 randomized patients, 96 were evaluable for efficacy and safety. No significant differences in efficacy were observed between the ondansetron- and granisetron-treated patients, evaluated by comparing the degree of nausea and distress, number of emetic episodes and overall control of emesis. The adverse effects were also comparable and no patients were removed from study because of severe toxicities. This trial demonstrates that ondansetron and granisetron are equally effective at preventing acute N/V associated with conditioning therapy frequently used for HSCT. The agent of choice should be based on drug acquisition cost or preference.

Antiemetics↗

Lignor process for acidic rock drainage treatment.

The process using lignosulfonates for acidic rock drainage (ARD) treatment is referred to as the Lignor process. Lignosulfonates are waste by-products produced in the sulfite pulping process. The present study has shown lignosulfonates are able to protect lime from developing an external surface coating, and hence to favor its dissociation. Further, the addition of lignosulfonates to ARD solutions increased the dotting and settling rate of the formed sludge. The capability of lignosulfonates to form stable metal-lignin complexes makes them very useful in retaining metal ions and thus improving the long-term stability of the sludge against leaching. The Lignor process involves metal sorption with lignosulfonates, ARD neutralization by lime to about pH 7, pH adjustment with caustic soda to 9.4 - 9.6, air oxidation to lower the pH to a desired level, and addition of a minimum amount of FeCl3 for further removal of dissolved metals. The Lignor process removes all concerned metals (especially Al and Mn) from the ARD of the Britannia Mine (located at Britannia Beach, British Columbia, Canada) to a level lower than the limits of the B.C. Regulations. Compared with the high-density sludge (HDS) process, the Lignor process has many advantages, such as considerable savings in lime consumption, greatly reduced sludge volume, and improved sludge stability.

Adsorption↗

Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis.

Approximately 15% of patients undergoing non-myeloablative allogeneic haematopoietical cell transplantation (NMHCT) develop steroid-refractory acute-graft versus host disease (aGVHD), a usually fatal complication. We encountered 18 cases of steroid-refractory aGVHD in 146 patients, undergoing NMHCT from a related human leucocyte antigen-compatible donor following cyclophosphamide/fludarabine-based conditioning. Our initial cohort of steroid-refractory aGVHD patients treated with antithymocyte globulin (ATG) and mycophenolate mofetil (regimen-1: n = 6) had high GVHD-related mortality. Therefore, we investigated an alternative strategy for subsequent patients developing this complication (regimen-2: n = 12), consisting of daclizumab (alone or combined with infliximab/ATG) and targeted broad spectrum antibacterial and aspergillus prophylaxis in conjunction with rapid tapering of steroids to minimize opportunistic infections. In a retrospective analysis, patients receiving regimen-2 were significantly more likely to have complete resolution of GVHD compared with those receiving regimen-1 [12/12 (100%) vs. 1/6 (17%); P < 0.001]. When compared with those receiving regimen-1, regimen-2 patients also had a higher probability of survival at day 100 (100% vs. 50%) and day 200 (73% vs. 17%) post-transplant, and improved overall survival (median 453 d vs. 42 d from aGVHD onset; P < 0.0001). GVHD-related mortality was 89% for regimen-1 patients vs. 17% for regimen-2 patients (P < 0.0001). These data suggest that a co-ordinated approach using immunoregulatory monoclonal antibodies, pre-emptive antimicrobial therapy and judicious steroid withdrawal can dramatically improve outcome in steroid-refractory aGVHD.

Adolescent↗

Homozygosity at the MTL locus in clinical strains of Candida albicans: karyotypic rearrangements and tetraploid formation.

One hundred and twenty Candida albicans clinical isolates from the late 1980s and early 1990s were examined for homozygosity at the MTL locus. Of these, 108 were heterozygous (MTLa/MTLalpha), whereas seven were MTLa and five were MTLalpha. Five of the homozygous isolates were able to switch to the opaque cell morphology, while opaque cells were not detectable among the remaining seven. Nevertheless, all but one of the isolates homozygous at the MTL locus were shown to mate and to yield cells containing markers from both parents; the non-mater was found to have a frameshift in the MTLalpha1 gene. In contrast to Saccharomyces cerevisiae, C. albicans homozygotes with no active MTL allele failed to mate rather than mating as a cells. There was no correlation between homozygosity and fluconazole resistance, mating and fluconazole resistance or switching and fluconazole resistance, in part because most of the strains were isolated before the widespread use of this antifungal agent, and only three were in fact drug resistant. Ten of the 12 homozygotes had rearranged karyotypes involving one or more homologue of chromosomes 4, 5, 6 and 7. We suggest that karyotypic rearrangement, drug resistance and homozygosity come about as the result of induction of hyper-recombination during the infection process; hence, they tend to occur together, but each is the independent result of the same event. Furthermore, as clinical strains can mate and form tetraploids, mating and marker exchange are likely to be a significant part of the life cycle of C. albicans in vivo.

Alleles↗

Bowel evisceration.

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Endometrial Neoplasms↗

Effect of H. pylori infection on the expression of cyclooxygenase-2 in human gastric mucosa.

Cyclooxygenase-1 is the primary isoform responsible for the production of cytoprotective prostaglandins (PGE(2) and PGI(2)) in the stomach. In contrast COX-2 is induced at the sites of inflammation. Using Helicobacter pylori infection as a model of inflammation, this study was designed to evaluate the effects of H. pylori infection on prostanoid synthesis and expression of COX-2 in human gastric mucosa. Prostaglandin (PGE(2)) and prostacyclin (PGI(2)) synthesis in gastric biopsies obtained from 21 patients undergoing diagnostic endoscopy, were determined. H. pylori was detected by CLO test, histology and culture. Biopsy samples were incubated either with NS-398, selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin (LPS) in order to induce COX-2 expression. Tissue was also analysed for COX-2 expression in vivo by immunohistochemistry. In 15 out of 21 patients, H. pylori was detected by at least two of the three methods. Higher levels of PGE(2) and PGI(2) were seen in patients infected with H. pylori (191+/-30 and 245+/-88ng/mg protein, respectively) compared with non-infected patients (77+/-17 and 120+/-36ng/mg protein, respectively). There was significant inhibition of PGE(2) and PGI(2) with aspirin in both H. pylori infected (28+/-6.6 and 53+/-43ng/mg, respectively) and in non-infected patients (16+/-7 and 12.5+/-3.5ng/mg protein, respectively). However, NS-398 and LPS did not alter prostaglandin function significantly. Immunohistochemistry in all patients irrespective of Hp status demonstrated expression of COX-2.Lower concentration of constitutive expression of COX-2 was detected in human gastric mucosa by immunohistochemistry, however, H. pylori infection failed to induce COX-2 protein. In addition, increased prostaglandin synthesis in Hp-infected patients appears to be COX-1 mediated rather than COX-2. Furthermore, failure of endotoxaemia-treated sample to produce more PGE(2) in the face of enhanced COX-2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX-1 mediated.

6-Ketoprostaglandin F1 alpha↗

A new technology for the treatment of mercury contaminated water and soils.

A new technology has been developed for the treatment of contaminated water and soils with lignin derivatives. It has been demonstrated that this technology can be used in the process of removal of high levels of mercury from water, and in the immobilization of leachable mercury in contaminated soils. Lignin derivatives contain an abundance of oxygen-containing functional groups such as phenolic, carboxyl, sulfonyl, alcoholic and enolic structures, which will form lignin-metal macromolecular complexes with high stability through ionic and coordinate covalent bonding. This feature is the basis for the application of lignin derivatives in the removal of metal contaminants from water and in the immobilization of leachable metal in soils or sediments. Tests have confirmed that lignin derivatives are capable of combining with a variety of metal ions including chromium, copper, lead, zinc, mercury, nickel and aluminum. In the new water treatment process, lignin derivatives are dissolved in mercury contaminated water to complex mercury in an exceptionally stable form of a lignin-mercury colloid. The lignin-mercury colloid is then coagulated through the addition of a flocculating agent such as ferric chloride. Under optimized conditions, a dean effluent is produced with a residual mercury level of less than 1 microg l(-1), together with a ferric sludge that is not leachable by TCLP, EPA Method 1311. In the new soil stabilization process, a new solid adsorbent of ferric-lignin is blended with mercury contaminated soil. This solid adsorbent can stabilize the soil by complexing with mercury and, thereby, greatly reduce the TCLP mercury of soil.

Adsorption↗

Application of ferric sludge to immobilize leachable mercury in soils and concrete.

A Hg-contaminated site in B.C. Province, Canada was caused by the previous operation of Hg-cell in chlor-alkali process for over 25 years. The soils and groundwater at the site are highly contaminated with mercury. An analysis of groundwater at the site has shown that most of the mercury is bonded with humic and fulvic acids (HFA) in colloidal form. The Hg-HFA colloids can be completely removed from the groundwater with ferric chloride treatment under optimized process conditions to form ferric sludge (FS), which is rendered non-leachable by standard TCLP (Toxicity Characteristic Leaching Procedure) test. The effluent discharged from a clarifier has achieved mercury levels of < 0.5 microkg l(-1). The studies of mercury adsorption characteristics of FS show it has low mercury leachability by TCLP, and great mercury adsorption capability. This feature is the basis for the application of FS to immobilization of leachable Hg-contaminants in solid wastes. Full-scale stabilization tests of Hg-contaminated soil have been carried out, and the time-based stability of the treated soil has been monitored by TCLP over a period of 60 days. All the results have shown a small variation in TCLP mercury levels within a range of 10-40 microg l(-1). Based on these results and with the approval of the B.C. Ministry of the Environment, 1850 tons of Hg-contaminated soils and 260 tons of Hg-contaminated concrete fines have been treated, stabilized with FS, and disposed in a non-hazardous waste disposal site.

Ferric Compounds↗

The founder mutation MSH2*1906G-->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population.

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair genes. We report here the identification and characterization of a founder mutation in MSH2 in the Ashkenazi Jewish population. We identified a nucleotide substitution, MSH2*1906G-->C, which results in a substitution of proline for alanine at codon 636 in the MSH2 protein. This allele was identified in 15 unrelated Ashkenazi Jewish families with HNPCC, most of which meet the Amsterdam criteria. Genotype analysis of 18 polymorphic loci within and flanking MSH2 suggested a single origin for the mutation. All colorectal cancers tested showed microsatellite instability and absence of MSH2 protein, by immunohistochemical analysis. In an analysis of a population-based incident series of 686 Ashkenazi Jews from Israel who have colorectal cancer, we identified 3 (0.44%) mutation carriers. Persons with a family history of colorectal or endometrial cancer were more likely to carry the mutation than were those without such a family history (P=.042), and those with colorectal cancer who carried the mutation were, on average, younger than affected individuals who did not carry it (P=.033). The mutation was not detected in either 566 unaffected Ashkenazi Jews from Israel or 1,022 control individuals from New York. In hospital-based series, the 1906C allele was identified in 5/463 Ashkenazi Jews with colorectal cancer, in 2/197 with endometrial cancer, and in 0/83 with ovarian cancer. When families identified by family history and in case series are included, 25 apparently unrelated Ashkenazi Jewish families have been found to harbor this mutation. Although this pathogenic mutation is not frequent in the Ashkenazi Jewish population (accounting for 2%-3% of colorectal cancer in those whose age at diagnosis is <60 years), it is highly penetrant and accounts for approximately one-third of HNPCC in Ashkenazi Jewish families that fulfill the Amsterdam criteria.

Alanine↗

Comparison between the Datex-Ohmeda M-COVX metabolic monitor and the Deltatrac II in mechanically ventilated patients.

OBJECTIVE: To compare the M-COVX and the Deltatrac II metabolic monitors under clinical conditions. DESIGN: Prospective clinical comparison. SETTING: A general Intensive Care Unit of a university hospital. PATIENTS: Twenty mechanically ventilated critically ill patients. INTERVENTIONS: The monitors were compared at FiO(2) 0.3, 0.5, and 0.7 in each patient where possible. MEASUREMENTS AND RESULTS: Pulmonary gas exchange measurements were recorded using the two monitors sequentially (Deltatrac(before), M-COVX, Deltatrac(after)). Each measurement consisted of five consecutive 1-min readings of VO(2) and VCO(2). We compared the Deltatrac(before) with the Deltatrac(after) and the mean of the Deltatrac with the M-COVX. There was no clinically significant bias between the two monitors for VO(2) or VCO(2) but the limits of agreement (LOA) were wide (bias +/-95% LOA: VCO(2) -13 +/- 30 ml/min, -8 +/- 36 ml/min, 7 +/- 50 ml/min; VO(2) -7 +/- 50 ml/min, -5 +/- 56 ml/min, 6 +/- 64 ml/min, at FiO(2) 0.3, 0.5, and 0.7, respectively). The Deltatrac before and after measurements displayed good agreement for VCO(2) but poorer agreement for VO(2) (bias +/- 95% LOA: VCO(2) 0 +/- 18 ml/min, -6 +/- 16 ml/min, -1 +/- 12 ml/min; VO(2) 2 +/- 12 ml/min, 3 +/- 38 ml/min, 10 +/- 42 ml/min, at FiO(2) 0.3, 0.5, and 0.7, respectively). Using within-patient standard deviation as a measure of reproducibility suggested that for VO(2) the M-COVX performed better than the Deltatrac at high FiO(2), and for VCO(2) Deltatrac was better at lower FiO(2). CONCLUSIONS: The M-COVX is a suitable integrated device for measuring metabolic gas exchange in ventilated patients.

Carbon Dioxide↗