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Biomedical subjects

A Goodwin

Publications and source records attributed to A Goodwin.

At least 19 recordsLinked to original sources
PubMed2007

Allogeneic bone marrow transplant for refractory mediastinal germ cell tumour: possible evidence of graft-versus-tumour effect.

Mediastinal germ cell tumours (GCT) carry a poor prognosis, particularly after relapse. We have reviewed the published reports of current treatments and describe a case with a cure after an allogeneic bone marrow transplant, which is not reported in the current published data. We believe that GCT may be susceptible to a graft-versus-tumour effect and suggest that patients with relapsed GCT be considered for allogeneic transplantation.

Adult↗
PubMed2005

Secondhand smoke, dietary fruit intake, road traffic exposures, and the prevalence of asthma: a cross-sectional study in young children.

The authors have investigated the independent effects of exposure to secondhand smoke, road vehicle traffic, and dietary fruit intake in a cross-sectional study of asthma in young children. They surveyed all children aged 4-6 years in 235 schools in the East Midlands and East of England regions of the United Kingdom in 2003. Data on respiratory symptoms, diagnoses and treatment, smoking in the home, and dietary fruit intake were collected by parental questionnaire. A geographic information system was used to map postcodes and determine the distance of the home from the nearest main road. Responses were obtained from 11,562 children. Wheeze in the past year and physician-diagnosed asthma were reported by 14.1% and 18.2%, respectively. Both of these outcomes were more common in children who lived with a smoker, and the prevalence of asthma increased with the number of smokers in the home. Asthma prevalence was not associated with proximity of the home to a main road or with dietary fruit intake. The authors conclude that, of the potential risk factors considered in this study, preventing secondhand smoke exposure may be the most effective way of preventing asthma.

Asthma↗
PubMed2004

Fish-tail plasty: a safe technique to improve cosmesis at the lateral end of mastectomy scars.

BACKGROUND AND AIMS: Redundant skin at the lateral end of a mastectomy scar can be unsightly and uncomfortable, especially in elderly obese patients. The aim of this study is to evaluate a technique of mastectomy wound closure designed to maximise cosmesis at the lateral end. PATIENTS AND METHODS: Thirty lateral skin flap advancements were performed in 28 patients. The procedure was performed primarily in 27 cases. In three cases a delayed scar revision was performed. Following anterior advancement of the skin overlying the latissimus dorsi muscle, two areas of redundant skin were excised and the wound closed in the shape of Y-plasty. RESULTS: The patients' mean age was 70.6 years (range 51-93) and the mean body mass index (BMI) 30.4 kg/m2 (range 21-35). The mean weight of the excised breast tissue was 1015 g (range 356-2003). The mean lengths of the two limbs of the Y-plasty were 5.3c m (range 3-10). The mean length of the base of the flap was 8.3 cm (range 4-14). One patient developed a small area of skin necrosis at the apex of the Y-plasty. Two further patients developed superficial wound infections. CONCLUSION: Fish-tail plasty is a safe and easy technique and may be recommended following mastectomy in obese patients to improve cosmesis and avoid discomfort caused by redundant skin.

Aged↗
PubMed2003

Community-acquired Legionnaires' disease in Nottingham--too many cases?

The aim of this study was to compare the incidence of community-acquired Legionnaires' Disease in Nottingham with England and Wales and to explore reasons for any difference observed. Based on data from the National Surveillance Scheme for Legionnaires' Disease (1980-1999), the rate of infection in England and Wales was 1.3 per million/year compared with 6.6 per million/ year in Nottingham. Domestic water samples were obtained from 41 (95%) of 43 Nottingham cases between 1997 and 2000. In 16 (39%) cases, Legionella sp. were cultured in significant quantities. Proximity to a cooling tower was examined using a 1:4 case-controlled analysis. No significant difference in the mean distance between place of residence to the nearest cooling tower was noted (cases 2.7 km vs. controls 2.3 km; P = 0.5). These data suggest that Nottingham does have a higher rate of legionella infection compared to national figures and that home water systems are a source.

Adolescent↗
PubMed2001

Involvement of Schizosaccharomyces pombe Srs2 in cellular responses to DNA damage.

In the budding yeast Saccharomyces cerevisiae the Srs2/RadH DNA helicase promotes survival after ultraviolet (UV) irradiation, and has been implicated in DNA repair, recombination and checkpoint signalling following DNA damage. A second helicase, Sgs1, is the S.cerevisiae homologue of the human BLM and WRN proteins, which are defective in cancer predisposition and/or premature ageing syndromes. Saccharomyces cerevisiae cells lacking both Srs2 and Sgs1 exhibit a severe growth defect. We have identified an Srs2 orthologue in the fission yeast Schizosaccharomyces pombe, and have investigated its role in responses to UV irradiation and inhibition of DNA replication. Deletion of fission yeast srs2 caused spontaneous hyper-recombination and UV sensitivity, and simultaneous deletion of the SGS1 homologue rqh1 caused a severe growth defect reminiscent of that seen in the equivalent S.cerevisiae mutant. However, unlike in budding yeast, inactivation of the homologous recombination pathway did not suppress this growth defect. Indeed, the homologous recombination pathway was required for maintenance of normal fission yeast viability in the absence of Srs2, and loss of homologous recombination and loss of Srs2 contributed additively to UV sensitivity. We conclude that Srs2 plays related, but not identical, roles in the two yeast species.

Amino Acid Sequence↗
PubMed2001

Selective spinal anesthesia for outpatient laparoscopy. V: pharmacoeconomic comparison vs general anesthesia.

PURPOSE: To compare the cost and effectiveness of small-dose spinal anesthesia (SP) with general anesthesia (GA) for outpatient laparoscopy. METHODS: A retrospective record analysis of 24 patients who received SP were compared with 28 patients who received GA in our Daycare centre. The costs of anesthesia and recovery were calculated, from an institutional perspective, using 1997 Canadian Dollar values. Effectiveness was measured in terms of time for anesthesia and recovery, and postoperative antiemetic and analgesic requirements. RESULTS: Both groups were well matched for age, weight, duration and type of surgery. The mean total cost for the SP group of $53.45 +/- 10.40 was no different from that for the GA group of $48.92 +/- 10.25 (95% CI -10.3, 1.2). Time to administer anesthesia was longer in the SP group with a mean time of 18 +/- 8 min compared with 10 +/- 3 min in the GA group (CI -11.3, -4.7). Recovery time in the PACU was longer in the SP group 123 +/- 51 min compared with 94 +/- 48 min (CI -56.6,-1.4). Postoperative antiemetic requirements were similar: 8% in SP group vs 14% in GA group, whereas analgesic requirements were less in the SP group with 25% receiving analgesia compared with 75% in the GA group (P < 0.05). CONCLUSION: The total cost of anesthesia and recovery using SP is similar to that for GA when used for outpatient laparoscopy. Spinal anesthesia was less effective than GA in time to administer anesthesia and in duration of recovery. Postoperative analgesic requirements were reduced using SP.

Adult↗
PubMed2000

Body image and psychological well-being in pregnancy. A comparison of exercisers and non-exercisers.

This study compared the perceptions of body image and psychological well-being between exercising and non-exercising pregnant women. A prospective longitudinal study was conducted with 65 nulliparous women (mean age years = 30.3, range = 23-39) who were allocated to 2 groups based on level of recreational exercise participation; 25 exercisers were compared with 18 non-exercisers. A self-report exercise history questionnaire and a 10 item Body Cathexis Scale were completed on two occasions during the pregnancy, at approximately 17 weeks and 30 weeks of gestation. The General Health Questionnaire (GHQ-28) was administered in late pregnancy. There was a significant difference between the exercise group and the non-exercise group in late pregnancy for some items on the Body Cathexis Scale. The exercise group had a lower level of probable caseness on the GHQ-28 with reduced frequency of somatic symptoms, anxiety and insomnia, and a higher level of psychological well-being.

Adult↗
PubMed2000

Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylori.

Helicobacter pylori is a human-pathogenic bacterial species that is subdivided geographically, with different genotypes predominating in different parts of the world. Here we test and extend an earlier conclusion that metronidazole (Mtz) resistance is due to mutation in rdxA (HP0954), which encodes a nitroreductase that converts Mtz from prodrug to bactericidal agent. We found that (i) rdxA genes PCR amplified from 50 representative Mtz(r) strains from previously unstudied populations in Asia, South Africa, Europe, and the Americas could, in each case, transform Mtz(s) H. pylori to Mtz(r); (ii) Mtz(r) mutant derivatives of a cultured Mtz(s) strain resulted from mutation in rdxA; and (iii) transformation of Mtz(s) strains with rdxA-null alleles usually resulted in moderate level Mtz resistance (16 microg/ml). However, resistance to higher Mtz levels was common among clinical isolates, a result that implicates at least one additional gene. Expression in Escherichia coli of frxA (HP0642; flavin oxidoreductase), an rdxA paralog, made this normally resistant species Mtz(s), and frxA inactivation enhanced Mtz resistance in rdxA-deficient cells but had little effect on the Mtz susceptibility of rdxA(+) cells. Strains carrying frxA-null and rdxA-null alleles could mutate to even higher resistance, a result implicating one or more additional genes in residual Mtz susceptibility and hyperresistance. We conclude that most Mtz resistance in H. pylori depends on rdxA inactivation, that mutations in frxA can enhance resistance, and that genes that confer Mtz resistance without rdxA inactivation are rare or nonexistent in H. pylori populations.

Amino Acid Substitution↗
PubMed2000

Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) (Nitroreductase) gene.

Much of the normal high sensitivity of wild-type Helicobacter pylori to metronidazole (Mtz) depends on rdxA (HP0954), a gene encoding a novel nitroreductase that catalyzes the conversion of Mtz from a harmless prodrug to a bactericidal agent. Here we report that levels of Mtz that partially inhibit growth stimulate forward mutation to rifampin resistance in rdxA(+) (Mtz(s)) and also in rdxA (Mtz(r)) H. pylori strains, and that expression of rdxA in Escherichia coli results in equivalent Mtz-induced mutation. A reversion test using defined lac tester strains of E. coli carrying rdxA(+) indicated that CG-to-GC transversions and AT-to-GC transitions are induced more frequently than other base substitutions. Alkaline gel electrophoretic tests showed that Mtz concentrations near or higher than the MIC for growth also caused DNA breakage in H. pylori and in E. coli carrying rdxA(+), suggesting that this damage may account for most of the bactericidal action of Mtz. Coculture of Mtz(s) H. pylori with E. coli (highly resistant to Mtz) in the presence of Mtz did not stimulate forward mutation in E. coli, indicating that the mutagenic and bactericidal products of Mtz metabolism do not diffuse significantly to neighboring (bystander) cells. Our results suggest that the widespread use of Mtz against other pathogens in people chronically infected with H. pylori may stimulate mutation and recombination in H. pylori, thereby speeding host-specific adaptation, the evolution of virulence, and the emergence of resistance against Mtz and other clinically useful antimicrobials.

Amino Acid Substitution↗
PubMed1999

Topoisomerase III is essential for accurate nuclear division in Schizosaccharomyces pombe.

Topoisomerases catalyse changes in the topological state of DNA and are required for many aspects of DNA metabolism. While the functions of topoisomerases I and II in eukaryotes are well established, the role of topoisomerase III remains poorly defined. We have identified a gene in the fission yeast Schizosaccharomyces pombe, designated top3 (+), which shows significant sequence similarity to genes encoding topoisomerase III enzymes in other eukaryotic species. In common with murine TOP3 alpha, but in contrast to Saccharomyces cerevisiae TOP3, the S.pombe top3 (+)gene is essential for long-term cell viability. Fission yeast haploid spores containing a disrupted top3 (+)gene germinate successfully, but then undergo only a limited number of cell divisions. Analysis of these top3 mutants revealed evidence of aberrant mitotic chromosome segregation, including the 'cut' phenotype, where septation is completed prior to nuclear division. Consistent with the existence of an intimate association (originally identified in S.cerevisiae ) between topoisomerase III and DNA helicases of the RecQ family, deletion of the rqh1 (+)gene encoding the only known RecQ helicase in S.pombe suppresses lethality in top3 mutants. This conservation of genetic interaction between two widely diverged yeasts suggests that the RecQ family helicases encoded by the Bloom's and Werner's syndrome genes are likely to act in concert with topoisomerase III isozymes in human cells. Our data are consistent with a model in which the association of a RecQ helicase and topoisomerase III is important for facilitating decatenation of late stage replicons to permit faithful chromosome segregation during anaphase.

Amino Acid Sequence↗
PubMed1999

Perinatal management of a neonate with airway obstruction caused by rhabdomyosarcoma of the tongue.

Intra-oral masses in neonates can seriously compromise the airway, potentially causing hypoxia and death if not recognized and managed appropriately. We report a case in which an intra-oral mass was diagnosed on antenatal ultrasound scan. Preparation for delivery involved a multidisciplinary team approach, with a strategy for management at delivery. The child was delivered by elective Caesarean section and had a patent airway. A tracheostomy was performed immediately after delivery. The infant underwent a debulking procedure 3 weeks after birth. A histological diagnosis of embryonal rhabdomyosarcoma was made and a course of chemotherapy commenced. The child had a partial response to treatment with considerable shrinkage of the tongue mass. We discuss the management options in neonates with intra-oral masses to provide an adequate airway and maintain fetal oxygenation. The differential diagnosis of fetal oral masses is reviewed.

Airway Obstruction↗
PubMed1999

Insertion of mini-IS605 and deletion of adjacent sequences in the nitroreductase (rdxA) gene cause metronidazole resistance in Helicobacter pylori NCTC11637.

We found that NCTC11637, the type strain of Helicobacter pylori, the causative agent of peptic ulcer disease and an early risk factor for gastric cancer, is metronidazole resistant. DNA transformation, PCR-based restriction analysis, and DNA sequencing collectively showed that the metronidazole resistance of this strain was due to mutation in rdxA (gene HP0954 in the full genome sequence of H. pylori 26695) and that resistance did not depend on mutation in any of the other genes that had previously been suggested: catalase (katA), ferredoxin (fdx), flavodoxin (fldA), pyruvate:flavodoxin oxidoreductase (porgammadeltaalphabeta), RecA (recA), or superoxide dismutase (sodB). This is in accord with another recent study that attributed metronidazole resistance to point mutations in rdxA. However, the mechanism of rdxA inactivation that we found in NCTC11637 is itself also novel: insertion of mini-IS605, one of the endogenous transposable elements of H. pylori, and deletion of adjacent DNA sequences including 462 bp of the 851-bp-long rdxA gene.

Amino Acid Sequence↗
PubMed1998

Isolation of a novel mycobacterium from an adolescent with cervical lymphadenitis.

A slow-growing mycobacterium was isolated from a cervical lymph node of an adolescent male. This isolate produced small, smooth, scotochromogenic colonies after 6 weeks of incubation at 25 degrees C and 30 degrees C (but not at 37 degrees C or 43 degrees C). The results of 16S-rRNA gene sequencing and high-performance liquid chromatography suggest that this isolate belongs to a hitherto unrecognised pathogenic species.

Adolescent↗
PubMed1998

Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase.

Metronidazole (Mtz) is a critical component of combination therapies that are used against Helicobacter pylori, the major cause of peptic ulcer disease. Many H. pylori strains are Mtz resistant (MtzR), however, and here we show that MtzR results from loss of oxygen-insensitive NADPH nitroreductase activity. The underlying gene (called 'rdxA') was identified in several steps: transformation of Mtz-susceptible (MtzS) H. pylori with cosmids from a MtzR strain, subcloning, polymerase chain reaction (PCR) and DNA sequencing. We also found that (i) E. coli (normally MtzR) was rendered MtzS by a functional H. pylori rdxA gene; (ii) introduction of rdxA on a shuttle vector plasmid into formerly MtzR H. pylori rendered it MtzS; and (iii) replacement of rdxA in MtzS H. pylori with an rdxA::camR null insertion allele resulted in a MtzR phenotype. The 630 bp rdxA genes of five pairs of H. pylori isolates from infections that were mixed (MtzR/MtzS), but uniform in overall genotype, were sequenced. In each case, the paired rdxA genes differed from one another by one to three base substitutions. Typical rdxA genes from unrelated isolates differ by 5% in DNA sequence. Therefore, the near identity of rdxA genes from paired MtzR and MtzS isolates implicates de novo mutation, rather than horizontal gene transfer in the development of MtzR. Horizontal gene transfer could readily be demonstrated under laboratory conditions with mutant rdxA alleles. RdxA is a homologue of the classical nitroreductases (CNRs) of the enteric bacteria, but differs in cysteine content (6 vs. 1 or 2 in CNRs) and isoelectric point (pI=7.99 vs. 5.4-5.6), which might account for its reduction of low redox drugs such as Mtz. We suggest that many rdxA (MtzR) mutations may have been selected by prior use of Mtz against other infections. H. pylori itself is an early risk factor for gastric cancer; the possibility that its carcinogenic effects are exacerbated by Mtz use, which is frequent in many societies, or the reduction of nitroaromatic compounds to toxic, mutagenic and carcinogenic products, may be of significant concern in public health.

Amino Acid Sequence↗
PubMed1998

Characterization of an acidic-pH-inducible stress protein (hsp70), a putative sulfatide binding adhesin, from Helicobacter pylori.

The in vitro glycolipid binding specificity of the gastric pathogen Helicobacter pylori is altered to include sulfated glycolipids (sulfatides) following brief exposure of the organism to acid pH typical of the stomach. This change is prevented by anti-hsp70 antibodies, suggesting that hsp70 may be a stress-induced surface adhesin, mediating sulfatide recognition. To facilitate investigation of the role of hsp70 in attachment, we have cloned and sequenced the H. pylori hsp70 gene (dnaK). The hsp70 gene was identified by probing a cosmid DNA library made from H. pylori 439 with a PCR amplicon generated with oligonucleotides synthesized to highly conserved regions of dnaK. The 1.9-kb H. pylori hsp70 gene encodes a product of 616 amino acids. Primer extension analysis revealed a single transcription start site, while Northern blot analysis established that hsp70 was preferentially induced by low pH rather than by heat shock. The ability of H. pylori to alter its glycolipid binding specificity following exposure to low pH by upregulating hsp70 and by expressing hsp70 on the bacterial surface may provide a survival advantage during periods of high acid stress.

Acids↗