PubMed Health⌕ Search

Biomedical subjects

J McMenamin

Publications and source records attributed to J McMenamin.

At least 19 recordsLinked to original sources
PubMed2006

P53 levels determine outcome during beta-catenin tumor initiation and metastasis in the mammary gland and male germ cells.

beta-Catenin, an oncogene, and P53, a tumor suppressor, are common targets of mutation in human cancers. It has been observed that P53 is often inactivated in tumors involving beta-catenin activation. In an attempt to model this situation in vivo, we crossed the previously characterized MMTV-DeltaN-beta-catenin mouse with the P53 knockout mouse. Female multiparous mice that carry the MMTV-DeltaN-beta-catenin transgene and that are heterozygous for P53 (Tg(DeltaN-betaCat)/+, P53+/-) display an increased tumor burden (2.05 vs 1.31 tumors/animal), with a generally more advanced pathology, and increased metastatic rate (39 vs 0%) relative to transgenic female mice that are wild type for P53 (Tg(DeltaN-betaCat)/+, P53+/+). These differences were not due to complete loss of P53 as only one of 21 tumors demonstrated loss of heterozygosity at the P53 locus. Furthermore, no mutations were present in tumors retaining a single wild-type allele. Tg(DeltaN-betaCat)/+, P53-/- male mice developed testicular teratomas and survived an average of 65 days, whereas non-Tg(DeltaN-betaCat), P53-/- males survived an average of 84 days. Sixty-two percent of Tg(DeltaN-betaCat), P53-/- mice developed testicular teratomas, whereas only 10% of the non-Tg(DeltaN-betaCat), P53-/- mice developed these tumors. These results indicate that the level of P53 and the tissue of origin are important factors in determining outcome of cancer caused by oncogene activation.

Animals↗
PubMed2006

Hospital transmission of hepatitis B virus in the absence of exposure prone procedures.

In February and in June 1998, two people developed acute hepatitis B following in-patient care in a district general hospital. Initial enquiries indicated their infections were not attributable to staff undertaking exposure-prone procedures (EPPs). We report the findings and implications of the subsequent investigation: a multi-disciplinary, multi-agency investigation, including molecular epidemiological analysis. Occupational Health records showed that staff involved in EPPs with the patients were HBsAg negative. No contact between the patients was identified nor were there failures in sterilization. The patients' HBV strains were identical, indicating a common source. A total of 231 out of 232 staff who might have treated either patient were tested for HBsAg; the remaining doctor, working abroad, was HBsAg- and HBeAg-positive and had the same HBV strain as the patients. On two occasions the doctor's hand had been cut while breaking glass vials, but there was no documentation linking these events to the two patients. The doctor had been vaccinated in 1993 and tested for anti-HBs prior to commencing work in 1997. The doctor was recalled to Occupational Health but did not attend and was not followed up. In total, 4948 patients potentially treated by the doctor received an explanatory letter and 3150 were tested for HBsAg. Only one was positive, and HBV sequencing showed no link to the doctor. Occasionally transmission of HBV from heath-care workers can occur in a non-EPP setting and the implications of this require examination by those setting national policy. Occupational Health Services should investigate clinical heath-care workers who do not respond to vaccination. They should ensure HBV carriers are identified and offer them appropriate advice to prevent transmission to patients.

Adult↗
PubMed2004

Incidence of hepatitis C virus infection and associated risk factors among Scottish prison inmates: a cohort study.

To gauge the incidence of hepatitis C virus (HCV) infection and associated risk factors among inmates during their imprisonment, the authors recruited adult males in a long-stay Scottish prison into a cohort study between April 1999 and October 2000. On two occasions (at 0 and 6 months), saliva was collected for anonymous HCV antibody testing and risk behavior data were obtained through a self-administered questionnaire. The participation rate was 85% at both initial recruitment (612/719) and follow-up (375/441; 171 men were ineligible for follow-up). For inmates who reported never having injected drugs, ever having injected drugs, having injected drugs during follow-up, and having shared needles/syringes during follow-up, HCV incidences per 100 person-years of incarceration risk were 1, 12, 19, and 27, respectively. Ever having injected drugs (relative risk = 13.0, 95% confidence interval: 1.5, 114.3) and having shared needles/syringes during follow-up (relative risk = 9.0, 95% confidence interval: 1.1, 71.7) were significantly associated with HCV seroconversion. The effectiveness of existing interventions, including the provision of bleach tablets for sterilizing injection equipment, was suboptimal. The development of methadone maintenance programs in prisons and the creation of drug courts to keep offending drug injectors out of prison might help to reduce transmission in this setting.

Adult↗
PubMed2004

Coats' plus: a progressive familial syndrome of bilateral Coats' disease, characteristic cerebral calcification, leukoencephalopathy, slow pre- and post-natal linear growth and defects of bone marrow and integument.

In 1988 we reported two sisters with bilateral Coats' disease, sparse hair, dystrophic nails, and primeval splashes of intracranial calcification. We now provide an update on this family documenting the occurrence of skeletal defects comprising abnormal bone marrow, osteopenia, and sclerosis with a tendency to fractures, a mixed cerebellar and extrapyramidal movement disorder, infrequent epileptic seizures, leukodystrophic changes, and postnatal growth failure. Additionally, we present two previously unreported individuals from Ireland and Switzerland with the identical disorder which we designate Coats' plus. Since our original publication a number of other authors have described, frequently as a "new" syndrome, cases with a variable combination of the same features observed in our patients. We review this literature and suggest that the phenotypic overlap with dyskeratosis congenita may provide a clue to the molecular aetiology of this multisystem disorder.

Alopecia↗
PubMed2004

Needs analysis for tele-neurophysiology in the Irish North-Western Health Board.

No clinical neurophysiology (CN) service is currently provided by the North-Western Health Board (NWHB) region in Ireland. Digital technology associated with CN is compatible with tele-neurophysiology service development and may increase the efficiency of patient care in remote areas. This study was conducted to assess the need for CN in the NWHB with a view to implementing a tele-neurophysiology service for the region. A retrospective audit of investigations performed at six CN departments in Dublin compared patient groups from regions with (Eastern Regional Health Authority--ERHA) and without (NWHB) local CN departments. 4954 records were audited. CN activity was lower than internationally expected (ERHA group 52% of expected, NWHB group 23% of expected). The 2 groups differ in the specialty of referring clinician (p < 0.0001). NWHB patients are more likely to be referred by clinicians outside their region (p < 0.0001) and wait longer for appointment (p < 0.0001). While there is an unmet demand for CN services in Ireland generally, the population of the NWHB is further disadvantaged. Tele-neurophysiology has the potential to provide fairer access to CN services across the country. The data from this study provide a baseline against which the outcome of investment in CN can be monitored and evaluated.

Chi-Square Distribution↗
PubMed2004

Childhood stroke following varicella infection.

Stroke in childhood remains unexplained in a significant proportion of those affected. We present a 4 year-old boy who presented with a stroke following a recent uncomplicated chickenpox infection. Varicella is increasingly recognized as a cause of acute ischaemic events in childhood and a recent history of chickenpox should be sought in children who present with a stroke.

Chickenpox↗
PubMed2002

2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency in a 23-year-old man.

2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (EC 1.1.1.178) deficiency is a recently described defect of isoleucine catabolism. The disorder is characterized by normal early development followed by a progressive loss of mental and motor skills. Deterioration may be rapid or may follow a slower decline with a possible stabilization of the disorder on a low-protein diet and appropriate medication. We report a 23-year-old man with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency with a very mild clinical course. He had apparently normal early development and remained relatively well until the age of 6 years, when he contracted measles. Following this illness, his motor skills and school progress deteriorated. At 15 years he had significant dysarthria, and generalized rigidity with some dystonic and unusual posturing. He was then treated with a low-protein high-carbohydrate diet with a good response in terms of balance and gait. At 18 years he was given benzhexol (Artane), increased slowly from 2 mg to 6 mg daily, resulting in improvement in tremor and dystonia. At 23 years he can dress himself and works in sheltered employment but remains severely dysarthric.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2001

Effect of combination therapy on immunologic progression of human immunodeficiency virus at a population level.

There is accumulating evidence from clinical trials and cohort studies that highly active antiretroviral combination therapy is effective at halting immunologic and clinical progression of human immunodeficiency virus (HIV). Its impact at a population level is less well known because the regimes may be difficult to tolerate and compliance poorer. The authors make use of population data for almost all of the HIV-infected people in Scotland in 1997 who were under clinical care and monitor their response to therapy during the first year when these effective treatments became widely available. More than two thirds of the HIV-positive patients were on some form of antiretroviral therapy during the year. The authors show that all treated groups, even those who were on changing regimes, showed net improvement in immunologic status during the year. For the group of patients on triple or quadruple therapy, there was an average increase of more than 100 CD4 cells/mm(3) over the year, with other treatment groups showing more modest, but significant, increases.

Anti-HIV Agents↗
PubMed2001

Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997.

OBJECTIVE: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe. METHODS: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop. RESULTS: Subpopulations of genetically related HIV strains were observed in Italy, France, Scotland and Spain, in contrast to the Netherlands, Austria and Switzerland. This difference between the two groups of countries suggests that the HIV epidemics amongst IDU in the latter group was caused by multiple virus introductions. In Edinburgh and the surrounding area, most IDU were infected with the same GGC strain over the 12-year study period. The epidemic among IDU in north-western Europe started with GGC viruses, whereas in south-western Europe non-GGC viruses predominated. This geographical separation has faded during the course of the epidemic, most likely because of virus exchange among IDU populations.

Base Sequence↗
PubMed2001

Rasmussen's syndrome associated with chronic brain stem encephalitis.

We report a 3-year-old boy with a clinical picture of Rasmussen's encephalitis who had clinical, radiological and pathological evidence of brain stem involvement resulting in death. In addition, there were unexpected neuropathological findings of severe bilateral mesial temporal sclerosis. We discuss the novel finding of brain stem involvement in this condition and the association with mesial temporal sclerosis.

Brain↗
PubMed2000

Risk of HIV transmission from patients to surgeons in the era of post-exposure prophylaxis.

The HIV prevalence, among patients either undergoing, or with the potential to undergo, surgery were estimated using data from unlinked anonymous HIV surveys of patients in Glasgow hospitals during 1992-1997 in order to quantify the risk of surgeons acquiring HIV occupationally in the era of post-exposure prophylaxis (PEP) availability. A range of prevalence rates was applied to data on other factors influencing risk; these comprised, i) the probability of a percutaneous injury from a sharp instrument used on an HIV infected patient resulting in HIV transmission, ii) the number of injuries sustained and iii) whether or not PEP was administered. On the basis of, for example, a surgeon sustaining three percutaneous injuries over 12 months and not taking PEP after each, the annual risks ranged from 1 in 2,000,000 for urological/renal surgeons to 1 in 200,000 for those performing general surgery/ENT/gynaecological procedures. The administration of PEP after each injury would reduce these rates to 1 in 10,000,000 and 1 in 1,000,000 respectively. The risk of surgeons acquiring HIV occupationally in a city which has an HIV prevalence typical of most urban areas in the UK, is 'minimal' or 'negligible'. In the context of such low risk and our limited knowledge of the adverse effects of PEP, the risk assessment to decide whether or not to give PEP should be well informed and consistent. Current guidelines to help physicians and affected healthcare workers in their decision making need to be improved.

Adolescent↗
PubMed2000

Prevalence of hepatitis C virus infection among injecting drug users in Glasgow 1990-1996: are current harm reduction strategies working?

OBJECTIVES: To determine the prevalence of HCV antibodies among injecting drug users and to gauge the effectiveness of needle/syringe exchange in preventing the transmission of HCV infection. METHODS: Between 1990-1994 and in 1996, annual cross-sectional surveys of injecting drug users in Glasgow were conducted. In order to ensure as representative a sample as possible, the 1949 respondents were recruited from both 'in-treatment' and 'out-of treatment' settings. Injectors were interviewed about their risk behaviours for blood-borne viruses and provided a saliva sample which was initially tested, anonymously, for HIV antibodies, and subsequently tested for hepatitis C infection. RESULTS: Among 1949 injectors, the prevalence of salivary antibodies, indicative of hepatitis C viraemia, was 61%(95%, confidence interval (CI) 59%-63%): the estimated prevalence of serum antibody positivity was 72%. Length of injecting, year of commencing drug injecting and the number of times in prison were predictive of antibody positivity. Thirty-one per cent of injectors who commenced their injecting after 1992, following the full establishment of needle/syringe exchange in the city, were salivary antibody positive, and the majority of their infections were acquired outside the prison setting. Respondents who began injecting after the introduction of needle/syringe exchange in the city were significantly less likely to test HCV antibody positive than those who commenced injecting prior to the advent of needle/syringe exchange, after adjusting for length of injecting career. CONCLUSION: The prevalence of HCV among injectors in Glasgow has decreased during the era of needle/syringe exchange. However, there is evidence to suggest that the incidence of infection remains high. Since the prevalence of hepatitis C viraemia among the city's injecting population is extremely high, ongoing transmission is inevitable unless more effective interventions are identified and implemented urgently.

Adolescent↗
PubMed2000

Hepatitis B immunisation of infants at risk.

A retrospective cohort review survey assessed hepatitis B immunisation uptake in at-risk infants over 4 years and a GP questionnaire identified the problems of poor communication and uncertainty of responsibility for immunisation as barriers to successful implementation of the immunisation programme. Incorporating appointments for hepatitis B immunisation within the national child immunisation recall system would help improve uptake but, in the meantime, a manual appointment system could be incorporated within existing child immunisation systems.

Family Practice↗
PubMed1999

Detection of antibodies against hepatitis C virus in saliva: a marker of viral replication.

Hepatitis C surveillance has been restricted owing to the lack of a sensitive antibody assay for saliva. The aim of our study was to develop and evaluate a screening assay for hepatitis C antibody in saliva specimens. Serum/saliva pairs were collected from 115 hepatitis C-positive patients. A modified hepatitis C antibody assay for saliva was developed and linked to testing carried out in the diagnostic laboratory. Correlation between the presence of antibody in serum and in saliva was poor (100% vs 85%). However, of 98 patients who were saliva antibody positive, 96 (98%) were also serum hepatitis C RNA positive and two (2%) were serum hepatitis C RNA negative. Hence, the correlation between a positive salivary antibody test and the serum hepatitis C RNA status of intravenous drug users suggests that this test could be used as a surrogate marker for hepatitis C viraemia in epidemiological studies.

Adult↗
PubMed1999

Hepatitis C antibody detection in dried blood spots.

In the UK, there have been few studies of the seroprevalence of antibodies to hepatitis C virus (anti-HCV). As part of an ongoing prevalence study of HCV in injecting drug users, we have developed a technique for detecting anti-HCV in blood spots dried on filter paper using a commercially available assay. Subjects with and without serum anti-HCV were studied. The manufacturer's recommended cut-off (CO) for a positive anti-HCV result is kit-dependent, and therefore a ratio of test result (T) to kit CO was used to standardize results. T/CO values greater than 0.99 had a sensitivity of 100% and a specificity of 87.5% for anti-HCV detection. T/CO values greater than 1.99 had a sensitivity of 97.2% and a specificity of 100%. Hence, testing dried blood spots may be useful for detecting anti-HCV in epidemiological studies and as a diagnostic test in patients with poor peripheral venous access.

Blood Specimen Collection↗