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Biomedical subjects

H Murphy

Publications and source records attributed to H Murphy.

At least 19 recordsLinked to original sources

Human microvascular endothelial cellular interaction with atomic N-doped DLC compared with Si-doped DLC thin films.

This article reports results of endothelial cell interaction with atom beam source N-doped a-C:H (diamond-like carbon, DLC) as it compares with that of Si-doped DLC thin films. The RF plasma source exhibits up to 40% N-dissociation and N-atomic fluxes of approximately 0.85 x 10(18) atoms/s, which ensures better atomic nitrogen incorporation. Two different types of nitrogen species (with and without the use of sweep plates to remove charged ions) were employed for nitrogen doping. The number of attached endothelial cells is highest on Si-DLC, followed by the N-DLC (where the sweep plates were used to remove ions), the N-DLC (without the use of sweep plates), undoped DLC, and finally the uncoated sample. The contact angle values for these films suggest that water contact angle is higher in the atomic nitrogen neutral films and Si-DLC films compared to the ionized-nitrogen specie doped films and undoped DLC thin films, suggesting that the more hydrophobic films, semiconducting films, and film with relieved stress have better interaction with human microvascular endothelial cells. It seems evident that N-doping increases the Raman I(D)/I(G) ratios, whereas N-neutral doping decreases it slightly and Si-doping decreases it even further. In this study, lower Raman I(D)/I(G) ratios are associated with increased sp(3)/sp(2) ratio, an increased H concentration, photoluminescence intensity, and a higher endothelial cellular adhesion. These investigations could be relevant to biocompatibility assessment of nanostructured biomaterials and tissue engineering.

Cell Adhesion↗

Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation.

Ovarian clear cell carcinoma (OCCC) accounts for a small but significant proportion of all ovarian cancers and is a distinct clinical and pathological entity. It tends to be associated with poorer response rates to chemotherapy and with a worse prognosis. Little is known about possible underlying genetic changes. DNA extracted from paraffin-embedded samples of 18 pure OCCC cases was analysed for genetic imbalances using comparative genomic hybridisation (CGH). All of the 18 cases showed genomic alterations. The mean number of alterations detected by CGH was 6 (range 1-15) indicating a moderate level of genetic instability. Chromosome deletions were more common than amplifications. The most prominent change involved chromosome 9 deletions in 10 cases (55%). This correlates with changes seen in other epithelial ovarian cancers. This deletion was confirmed using microsatellite markers to assess loss of heterozygosity (LOH) at four separate loci on chromosome 9. The most distinct region of loss detected was around the IFNA marker at 9p21 with 41% (11 out of 27 cases) LOH. Other frequent deletions involved 1p (five out of 18; 28%); 11q (four out of 18; 22%) and 16 (five out of 18; 28%). Amplification was most common at chromosome 3 (six out of 18; 33%); 13q (four out of 18; 22%) and 15 (three out of 18; 17%). No high-level amplifications were identified. These features may serve as useful prognostic indicators in the management of OCCC.

Adenocarcinoma, Clear Cell↗

Tissue-engineered dermal skin grafting in the treatment of ulcerated necrobiosis lipoidica.

Necrobiosis lipoidica is a well recognized but comparatively rare cutaneous complication of diabetes mellitus. The aetiology is probably multifactorial with microangiopathy, immune complex formation, abnormal collagen synthesis and breakdown, and altered haemostasis all thought to play a part. Necrobiosis lipoidica often proves very resistant to treatment. We report a case of a 44-year-old woman with ulcerated necrobiosis lipoidica that healed following grafting with a tissue-engineered living dermal tissue.

Adult↗

Successful treatment with ICSI of infertility caused by azoospermia associated with adrenal rests in the testes: case report.

Congenital adrenal hyperplasia (CAH) is a well-recognized, but uncommon, cause of azoospermia and infertility in men. Commonly this is due to undertreatment of excessive adrenal androgen secretion which suppresses gonadotrophin stimulation of the testes. A less common complication of CAH is development of adrenal tissue within the testes; this is important to recognize because it may be confused with malignancy leading to unnecessary surgery. In this case report, a man is described with simple virilizing CAH due to 21-hydroxylase deficiency who presented with azoospermia and was found to have adrenal rests. Investigations concluded that there was adequate adrenal suppression with glucocorticoids and that azoospermia was due to obstruction by adrenal rest tissue, strategically situated at the hilum of the testes. Spermatozoa were able to be retrieved by testicular aspiration from the man and these were used to successfully establish a pregnancy using intracytoplasmic sperm injection of his wife's oocytes.

Adrenal Hyperplasia, Congenital↗

Treatment of chronic digital septic tenosynovitis in 12 horses by modified open annular ligament desmotomy and passive open drainage.

A modified open annular ligament desmotomy followed by passive open drainage was used to treat 12 horses with chronic digital septic tenosynovitis due to trauma in the form of open wounds or self-sealing punctures. The surgical approach included complete transection of the palmar/plantar annular ligament of the fetlock and proximal digital annular ligament, which facilitated the removal of fibrin, selective debridement and synovectomy, followed by lavage of the digital sheath. The incision was partially closed leaving a 2 cm gap open distally to allow for passive open drainage. Gentamicin was administered intrathecally during surgery. Postoperatively the horses received ceftiofur and non-steroidal anti-inflammatory drugs. A sterile bandage was used to protect the wound until the gap had healed completely by second intention. Infection was controlled in 11 of the horses which all returned to their previous levels of work, but one horse was euthanased as a result of the persistence of the infection and financial considerations.

Animals↗

Eradication of vancomycin resistant Enterococcus faecium from a paediatric oncology unit and prevalence of colonization in hospitalized and community-based children.

We previously reported an outbreak of vancomycin resistant enterococci (VRE) in a paediatric oncology unit in December 1995 which was associated with widespread environmental contamination of the unit with VRE. We undertook this study to evaluate the effectiveness of the infection control policy instituted subsequent to the outbreak and to investigate the underlying prevalence of VRE colonization in hospitalized, outpatient and community-based children. We sought to establish the molecular similarity of VRE isolates from the study. Stool specimens were obtained from outpatients at risk of VRE, hospital inpatients and from healthy community-based children. VRE colonization was eradicated from the inpatient unit within 11 months, but in outpatients, 16 months after the outbreak, 4 of 137 (2.9 %) attending oncology outpatients, 5 of 65 (7.7%) with cystic fibrosis and 1 of 12 (8.3 %) with liver disease were found to be colonized with VRE. The isolates were all Enterococcus faecium, Van A phenotype except one E. casseliflavus of the Van C phenotype. All were unique in SmaI DNA macrorestriction patterns with the exception of two isolates, which were similar to the original outbreak strain and three further isolates of a single strain but which differed from the outbreak strain. Of 315 hospital inpatients, 2.5 % were colonized with VRE of the Van C resistance phenotype but VRE was not detected in 116 healthy, community-based children. We conclude that effective strategies can successfully control spread of VRE but despite a low prevalence of VRE colonization in hospital patients and in community-based children, outbreaks can occur when infection control practices are not optimal. Continued vigilance to detect VRE and limit spread within hospitals is therefore necessary.

Adolescent↗

Depression, illness perception and coping in rheumatoid arthritis.

This study aimed to establish the relationship between depression, illness perception, coping strategies, and adverse childhood events in rheumatoid arthritis patients. Sixty-two out-patients with rheumatoid arthritis (RA) completed the Hospital Anxiety and Depression Scale, Illness Perception Questionnaire, London Coping with Rheumatoid Arthritis Questionnaire, and Childhood Development Questionnaire, and underwent a clinical assessment of their physical state. Depressed patients were more disabled than the nondepressed, had a more negative view of their illness, and used more negative coping strategies. There was no association between depression and childhood adversity. Once disability was controlled for, there continued to be a significant correlation between depression and: (i) viewing the consequences of the illness negatively (Spearman's correlation coefficient [r]=0.37, p=0.003); and (ii) the perceived ability to control the illness (r= -0.26, p=0.04). The relationship between depression and negative coping strategies became insignificant. This study indicates the close relationship between depression and a negative view of the illness.

Adaptation, Psychological↗

An assessment of paediatric diabetes care in three centres in Russia and in Southampton, UK. The Paediatric Teams in Moscow, Tula, Tambov, Southampton.

AIMS: Young people in Russia with diabetes have an increased morbidity and a 10-fold increase in mortality compared with many European countries. This joint international study was set up to compare of care and outcomes against published guidelines in three Russian centres and one UK centre. METHODS: An assessment of the diabetic care of 368 children, based on the principles of the St Vincent Declaration, was undertaken in each centre. Data on prevalence, management, control and complications were collected in young people with diabetes < 16 years of age in each of the four centres over a 4-week period. RESULTS: The prevalence of diabetes was greater in Southampton (1:702 vs. 1:1378). At diagnosis Russian children had a higher incidence of ketoacidosis (69 vs. 29%) and stayed in hospital longer (30 vs. 3 days). In management Russian children received more injections per day (5 vs. 2). There was no significant difference in insulin dose for those under 10 years between countries (Southampton 0.69 U/kg vs. Russian 0.73 U/kg, P=NS). Older Russian children did not increase their insulin dosage, while children over 10 years in Southampton received significantly more insulin than the Russian children (Southampton 1.0 U/kg vs. Russian 0.77 U/kg, P< or =0.001). Twenty-nine per cent of the Russian children reported that they had insufficient insulin and 14% had to buy extra. HbA1c was higher in the Russian children (9.8% vs. 8.3%), increasing significantly with age. The Russian children showed a height deficit which correlated with HbA1c and diabetes duration. The Southampton children were heavier and with a higher body-mass index and their HbA1c did not rise similarly as in Russia. Severe hypoglycaemia was more common in the Southampton children (32 vs. 12%). Retinopathy was reported in 12% of the Russian children (Southampton 0%) and systolic blood pressure > 95th centile in 21% (Southampton 8%). CONCLUSIONS: This study demonstrates a significant difference in diabetic control and complications between the two countries which could be partially explained by a decreased availability and prescribing of insulin and blood glucose monitoring in Russia. Southampton has an education and management policy based on ambulatory care resulting in reduced hospital stay.

Adolescent↗

Control of a nosocomial outbreak of vancomycin resistant Enterococcus faecium in a paediatric oncology unit: risk factors for colonisation.

UNLABELLED: In order to determine the extent of vancomycin resistant enterococcus (VRE) colonisation within a paediatric oncology unit, the risk factors for the acquisition of the organism, the molecular epidemiology of the isolates and the impact of infection control measures, extensive patient and environmental surveillance was undertaken with identification, antibiotic susceptibility testing and pulsed-field gel electrophoresis (PFGE) of all VRE isolates. A matched case control study was carried out. Fourteen patients (19% of screened patients) with VRE colonisation were identified (12 with Enterococcus faecium). All isolates manifested the Van A phenotype. Extensive environmental contamination with VRE was present. PFGE of E. faecium isolates from 10 patients and from five of six environmental cultures revealed patterns suggesting genetic relatedness. Following comparison of the 14 cases with 41 controls matched for age (+/- 4 years) and cohabitation on the oncology unit, risk factors for colonisation with VRE included duration of neutropenia, (OR, 3.72; 95% CI, 1.0-13.1), and antibiotic therapy, (OR, 4.07; 95% CI, 1.08-15.3), the number of antibiotic agents received, (OR, 8.4; 95% CI, 1.34-34.3) and the duration of therapy with amikacin, (OR, 10.7; 95% CI, 1.4-81.5), ceftazidime, (OR, 11.5; 95% CI, 2.2 59.9) or teicoplanin, (OR, 12.3; 95% CI, 2.25-67.4). Implementation of stringent infection control measures reduced environmental contamination from 25% of samples in week 1 to none in week 11. Two additional colonised patients were identified during the subsequent 6 months. CONCLUSION: Risk factors for VRE colonization in paediatric oncology patients included duration of neutropenia, duration of any antibiotic therapy, exposure to ceftazidime, amikacin or teicoplanin and the number of antibiotics used. The study suggests that environmental contamination played an important role in patient-to-patient transmission of VRE and interventions including implementation of infection control measures were associated with a decreased incidence of gastro-intestinal colonisation.

Adolescent↗

Guanosine tetraphosphate (ppGpp)-mediated inhibition of the activity of the bacteriophage lambda pR promoter in Escherichia coli.

It was previously demonstrated that the activity of bacteriophage lambda promoter pR is decreased in wild-type Escherichia coli cells starved for amino acids (during the stringent response). Since pR activity is necessary for the transcriptional activation of ori lambda, this leads to inhibition of the replication of plasmids derived from phage lambda. These results led to the proposal that the pR promoter susceptible to control by the stringent response. However, subsequent studies demonstrated that this promoter is activated by the host dnaA gene product and since the dnaA promoter was reported to be controlled by the stringent response, it is possible that the inhibition of pR activity in amino acid-starved cells is indirect, and results from the impairment of DnaA-mediated transcriptional activation. Here we present evidence that pR is negatively regulated by ppGpp, even when DnaA protein is provided in excess as well as in cells devoid of DnaA function. We have checked that the level of ppGpp is increased during prolonged (up to 4 h) starvation for isoleucine in relA+ cells but not in the relA- mutant. At the same time we observed inhibition of lambda plasmid replication during the stringent, but not relaxed, response, even when DnaA was overproduced. Finally, we found that the activity of a pR-lacZ fusion is inhibited after gratuitously induced overproduction of ppGpp in unstarved cells, irrespective of the status of the dnaA gene product. We conclude that the activity of the pR promoter is inhibited directly by ppGpp.

Bacterial Proteins↗

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a Dublin paediatric hospital.

Klebsiella pneumoniae resistant to third-generation cephalosporins and gentamicin was isolated from two patients in a paediatric intensive care unit within a two-week period. The double-disc diffusion test indicated the presence of an extended-spectrum beta-lactamase (ESBL). The unit was closed to admissions, and stringent infection control procedures were implemented. Environmental screening and screening of staff and patients on the unit were commenced. Two weeks later, K. pneumoniae with an identical antibiogram was isolated from the urine of a patient in a different ward. Blood-culture isolates possessed the K16 antigen, while the urine isolate was non-typeable. The isolates were shown to be similar when banding patterns of XbaI chromosomal DNA digests were compared. The resistance to the extended-spectrum cephalosporins was shown to be transferable in association with a large plasmid > 98 mDa. Resistance to gentamicin always co-transferred with beta-lactamase resistance and appeared to be encoded by the same plasmid.

Child, Preschool↗

Guanosine tetra- and pentaphosphate promote accumulation of inorganic polyphosphate in Escherichia coli.

High levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), generated in response to amino acid starvation in Escherichia coli, lead to massive accumulations of inorganic polyphosphate (polyP). Inasmuch as the activities of the principal enzymes that synthesize and degrade polyP fluctuate only slightly, the polyP accumulation can be attributed to a singular and profound inhibition by pppGpp and/or ppGpp of the hydrolytic breakdown of polyP by exopolyphosphatase, thereby blocking the dynamic turnover of polyP. The Ki values of 10 microM for pppGpp and 200 microM for ppGpp are far below the concentrations of these nucleotides in nutritionally stressed cells. In the complex metabolic network of pppGpp and ppGpp, the greater inhibitory effect of pppGpp (compared with ppGpp) leading to the accumulation of polyP, may have some significance in the relative roles played by these regulatory compounds.

Acid Anhydride Hydrolases↗

Gestational diabetes mellitus: antenatal variables as predictors of postpartum glucose intolerance.

OBJECTIVE: To determine whether antepartum variables can predict postpartum glucose intolerance. METHODS: Glucose tolerance was assessed 6 weeks postpartum in 94 of 238 women with gestational diabetes using a 2-hour, 75-g oral glucose tolerance test (GTT). Selected antepartum variables were analyzed for predictive ability for postpartum glucose intolerance. RESULTS: Of 238 patients, 94 (39%) returned for a GTT. Those returning and those not returning were similar in all variables. Postpartum glucose intolerance occurred in 34%: impaired glucose tolerance in 18%, overt diabetes in 16%. No single maternal, intrapartum, or neonatal variable was predictive of postpartum glucose intolerance in all cases. Predictive variables included: requirement for insulin (insulin versus diet: 25 versus 3% impaired glucose tolerance, 26 versus 0% diabetes; P = .001), poor glycemic control (any 2-hour postprandial blood sugar level of 150 mg/dL or higher: 34 versus 5% diabetes; P = .005), and the 50-g GTT value (200 mg/dL or higher: 32 versus 6% diabetes; P = .01). For insulin requirement, the relative risk (RR) was 17.28 (95% confidence interval [CI] 2.46-121.45), and for the above three variables combined, the RR was 19.68 (95% CI 2.88-134.2). When the insulin dose was at least 100 U/day, all patients had abnormal glucose tolerance postpartum (RR = 34.00, 95% CI 4.93-234.39). CONCLUSIONS: Postpartum glucose screening is not warranted for women at low risk who do not require insulin during pregnancy. The incidence of postpartum glucose intolerance in this group is very low. Women with risk factors should receive postpartum screening. Patients receiving at least 100 U/day of insulin have a 100% incidence of postpartum glucose intolerance.

Adult↗

Health after childbirth: a comparison of normal and assisted vaginal delivery.

413 women were included in the study: 100 who had had a normal delivery and 313 who had participated in a randomised controlled comparison of forceps or ventouse delivery. The study comprised a questionnaire and assessment at 24-48 hours after delivery and a questionnaire in the second year after delivery. There was significantly more morbidity in the women in the instrumental delivery group compared to women in the normal delivery group at both the early assessment and long-term follow-up.

Adult↗

The nucleotide sequence of recG, the distal spo operon gene in Escherichia coli K-12.

A gene is identified in the Escherichia coli K-12 spo operon as recG. Previously identified genes in the spo operon were spoS, alias rpoZ, encoding the omega (omega) subunit of RNA polymerase, as well as the spoT gene encoding the major cellular source of guanosine 3',5'-bispyrophosphate hydrolase activity. The gene order within the spo operon is: spoS (rpoZ), spoT, spoU, recG. A convergent gltS gene is present beyond the spo operon. Mutants bearing recG deletion-insertion alleles display mild sensitivities to both ultraviolet irradiation and to mitomycin C, which is expected to be due to a known recG insertion allele. Deletion-insertion mutations in upstream operon genes (spoT and spoU) show polar effects on these assays of recG function. The deduced 693-amino acid (aa) RecG sequence shows a weak, but significant, relatedness to aa sequence motifs previously reported for putative helicases involved in replication, recombination, and DNA repair.

Amino Acid Sequence↗