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Biomedical subjects

J Gill

Publications and source records attributed to J Gill.

At least 19 recordsLinked to original sources
PubMed2006

Assay of HIV gp41 amino acid sequence to identify baseline variation and mutation development in patients with virologic failure on enfuvirtide.

In this study, we retrospectively assessed a gp41 genotypic assay in 404 enfuvirtide-naïve individuals (340 clade B, 64 non-B clade) to determine the prevalence of baseline polymorphisms and in 41 patients virologically failing enfuvirtide to determine correlates of resistance to this agent. Conserved and polymorphic regions of gp41 were identified in clade B isolates, with 127 of 328 codons (38.7%) being highly conserved (<1.0% variation) and 74 of 328 codons (22.6%) being partially conserved (1.0-5.0% variation). Polymorphisms were observed throughout gp41 in non-B clade virus sequences compared to the clade B reference strain, ranging from 53 natural substitutions in clade D to 76 in clade A. Insertions were common at positions 3, 105, 215 and 276. In the patients failing enfuvirtide, mutations were detected in the 10 amino acid region at positions 36-45 in all plasma virus sequences. Six additional mutations were selected outside of the common region which may be clinically significant at positions 33, 73, 75, 126, and 138. Two or three mutations at positions 36-45 were observed in the majority of plasma virus sequences from patients with virologic failure following the use of enfuvirtide. Further study is required to determine the clinical relevance of the clade related polymorphisms and the new mutations identified in the patients with virologic failure.

Adult↗
PubMed2005

Methicillin-resistant Staphylococcus aureus: awareness and perceptions.

The purpose of this study was to investigate levels of awareness and the perceived risk of contracting methicillin-resistant Staphylococcus aureus (MRSA) amongst patients/visitors and employees of the UK National Health Service (NHS). Differences between the two cohorts were also investigated, particularly sources of information about MRSA. In March 2005, a piloted questionnaire was circulated to 50 patients/visitors and 100 NHS employees (25 doctors, 25 nurses, 25 domestics and 25 porters). No information was returned from porters, but the overall response rate was 67%. There was a high level of awareness of MRSA among both patients/visitors (94%) and NHS employees (100%). General media was the most common source of information for patients/visitors (68%) compared with 24% of NHS employees (P < 0.01). Perceived risk of contracting MRSA was very similar among patients/visitors and NHS employees (34% vs 35%, P > 0.10). Fifty-two percent of doctors felt that they were at risk compared with 13% of domestic employees. In conclusion, this study showed a high level of awareness among the general public and healthcare workers alike.

Adult↗
PubMed2005

Metabolic syndrome and risk of coronary heart disease in a Pakistani cohort.

OBJECTIVE: To assess the relation of the metabolic insulin resistance syndrome (M-IRS) with coronary heart disease (CHD) in Pakistani patients. SUBJECTS: 200 patients with angiographic disease (CHD(+)) matched with 200 patients with chest pain without occlusive disease (CHD(-)). DESIGN: Prospective case-control study. SETTING: Tertiary referral cardiology unit in Pakistan. RESULTS: M-IRS was present in 37% of CHD(+) versus 27% of CHD(-) patients by criteria for white patients or 47% versus 42%, respectively, by Asian criteria (p < 0.001). After adjustment for other risk factors, M-IRS was not a significant predictor for CHD or angiographic disease. Age (p = 0.03), smoking (p < 0.001), diabetes-years (p = 0.003), sialic acid (p = 0.01), and creatinine (p = 0.008) accounted for the excess risk of CHD. Similarly, age (p = 0.005), creatinine (p < 0.001), cigarette pack-years (p = 0.02), diabetes-years (p = 0.003), and sialic acid (p = 0.08) were predictors of greater angiographic disease. M-IRS differed between Pakistani and white patients, as waist circumference correlated weakly (r = -0.03-0.08, p = 0.45-0.52) with triglycerides, high density lipoprotein cholesterol, systolic blood pressure, or glucose. Sialic acid was the only inflammatory marker associated with M-IRS. CONCLUSIONS: Despite strong associations between individual risk factors associated with M-IRS and a univariate association between M-IRS and CHD in native Pakistanis, the principal discriminant risk factors in this group are age, smoking, inflammation, diabetes-years, and impaired renal function. The poor sensitivity of M-IRS for CHD reflects the high underlying prevalence of M-IRS, thus reducing sensitivity, confounding by other urban lifestyle traits, or a lack of association of waist circumference with M-IRS risk factors. The definition of M-IRS may have to be revised to increase its power as a discriminant risk factor for CHD in Pakistani populations.

Coronary Artery Disease↗
PubMed2004

Antibodies to Neospora caninum in the blood of European bison (Bison bonasus bonasus L.) living in Poland.

The prevalence of antibodies to Neospora caninum was examined in European bison (Bison bonasus bonasus L.) living in free and fenced areas in Poland. Sera of 320 European bison, different ages and sexes, from breeding areas in Poland were tested for N. caninum antibodies using ELISA test. Positive antibody responses were found in 23 bison (prevalence 7.3%). Additionally, all positive sera were tested by Western blot to verify the ELISA results. The Western blot results confirmed the presence of antibodies to Neospora tachyzoites antigens in all 23 sera tested. The antibodies were detected against a wide range of NC-1 tachyzoite antigens. The antibody responses were directed against proteins at: 9.5, 17, 21, 27, 31, 36.5, 38, 40, 43, 47, 48.5, 53.5 and 58 kDa. The most heavily stained bands had molecular weights of 9.5, 17, 27 and 58 kDa. The most important is that antibody to N. caninum was detected for the first time in sera from bison cow shot in 1988. It is the year of recognition of this protozoan parasite. Our results indicate strongly the presence of N. caninum in European bison in Poland and suggest that a sylvatic cycle of N. caninum can exist. However, further studies are needed to evaluate the existence of a sylvatic cycle of N. caninum. The study on the effect of the infection on the health status and conservation of European bison should be taken under consideration too.

Animals↗
PubMed2004

Anticancer drug response and expression of molecular markers in early-passage xenotransplanted colon carcinomas.

Despite some success in the treatment of colorectal carcinomas, novel rational therapies targeting specific cancer-related molecules are under development and urgently needed. These approaches need careful preclinical evaluation in models that closely mirror the clinical situation. Therefore, we established a panel of 15 xenotransplantable tumours directly from fresh surgical material. We showed that both the histology and expression of tumour-associated markers (Epithelial Cell Adhesion molecule (EpCAM), E-cadherin, carcinoembryonic antigen (CEA)) could be maintained during passaging in nude mice. Xenotransplanted tumours were characterised for chemosensitivity and revealed a response rate of 5/15 (33%) for 5-fluorouracil (5-FU), 15/15 (100%) for irinotecan and 8/14 (57%) for oxaliplatin. 5 patients out of 15 were treated with cytostatics because of synchronous metastases. The response to chemotherapy in these patients coincided very closely with the response of the individual xenografts. All of the xenografts expressed the proliferation marker Ki67 and the nuclear enzyme, Topoisomerase IIalpha (Topo IIalpha) at the protein level. Most of the xenografts also expressed the tumour suppressor, p53 (9/14) and the nuclear enzyme Topoisomerase Ialpha (Topo Ialpha) (13/14) at the protein level. Interestingly, the presence of a K-ras mutation in codon 12 (5/15 xenografts) coincided with a low response rate towards oxaliplatin. This observation needs further confirmation using a larger number of tumours. In conclusion, we were able to establish transplantable xenografts suitable to mimic the clinical situation. These well characterised models are useful tools for the preclinical development of novel therapeutic approaches and for investigating translational research aspects.

Animals↗
PubMed2003

Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies.

BACKGROUND: We examined whether the initial virological and immunological response to highly active antiretroviral treatment (HAART) is prognostic in patients with HIV-1 who start HAART. METHODS: We analysed 13 cohort studies from Europe and North America including 9323 adult treatment-naive patients who were starting HAART with a combination of at least three drugs. We modelled clinical progression from month 6 after starting HAART, taking into account CD4 count and HIV-1 RNA measured at baseline and 6 months. FINDINGS: During 13408 years of follow-up 152 patients died and 874 developed AIDS or died. Compared with patients who had a 6-month CD4 count of fewer than 25 cells/microL, adjusted hazard ratios for AIDS or death were 0.55 (95%CI 0.32-0.96) for 25-49 cells/microL, 0.62 (0.40-0.96) for 50-99 cells/microL, 0.42 (0.28-0.64) for 100-199 cells/microL, 0.25 (0.16-0.38) for 200-349 cells/microL, and 0.18 (0.11-0.29) for 350 or more cells/microL at 6 months. Compared with patients who had a 6-month HIV-1 RNA of 100000 copies/mL or greater, adjusted hazard ratios for AIDS or death were 0.59 (0.41-0.86) for 10000-99999 copies/mL, 0.42 (0.29-0.61) for 500-9999 copies/mL, and 0.29 (0.21-0.39) for 6-month HIV-1 RNA of 500 copies/mL or fewer. Baseline CD4 and HIV-1 RNA were not associated with progression after controlling for 6-month concentrations. The probability of progression at 3 years ranged from 2.4% in the patients in the lowest-risk stratum to 83% in patients in the highest-risk stratum. INTERPRETATION: At 6 months after starting HAART, the current CD4 cell count and viral load, but not values at baseline, are strongly associated with subsequent disease progression. Our findings should inform guidelines on when to modify HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2003

The effect of endocardial defibrillator shocks on basic atrial electrophysiology in man. Is post cardioversion atrial electrical 'remodelling' artefact?

AIMS: To determine the effect of an endocardial DC shock on the basic electrophysiology of the human atrium if delivered in sinus rhythm. METHODS AND RESULTS: A 5J endocardial R wave synchronized DC shock was delivered in 10 patients in stable sinus rhythm during ICD implantation for ventricular arrhythmias. There was no prior history of atrial fibrillation. Monophasic action potential duration (APD) and atrial effective refractory periods (AERP) were evaluated before, 1 min post DC shock, and 15 min post shock. These parameters were assessed at basic cycle lengths and at atrial paced cycle lengths of 600 ms and 400 ms at two right atrial sites; mid lateral right atrial wall (MRLA) and the right atrial appendage (RAA). There were no significant differences in APD 90, AERP or atrial refractory dispersion at any site or drive cycle length before, immediately after or 15 min after shock delivery. CONCLUSIONS: There are no significant changes in basic electrophysiological parameters following a DC shock delivered in sinus rhythm in patients with no prior history of atrial fibrillation. This suggests that atrial electrical remodelling occurs as a result of atrial fibrillation and is unrelated to shock artefact.

Artifacts↗
PubMed2003

Gastroenterological research in domestic animals--past, present and future perspectives.

The gastrointestinal research in domestic animals in Poland is briefly discussed in the section. The history starts over seventy years ago with the creation of the Department of Animal Physiology at the Veterinary Faculty of Warsaw University. Professor B. Gutowski, the first head of the Department, and his pupils established the School of Gastrointestinal Physiology; renowned for the achievements in physiology of digestion, gastrointestinal motility, pancreas and liver functions, and comparative physiology of domestic ruminants and wild animals. After the WWII the gastrointestinal research has also been initiated in the newly established faculties of veterinary and animal science of the agricultural universities in Lublin (motility, composition of pepsinogen, biliary and pancreas secretion, vitamin and microelement absorption), Szczecin (lipid absorption, lymph formation), Wrocław (gastrointestinal and gall bladder motility, bile secretion) as well as in the Institute of Animal Physiology and Nutrition of the Polish Academy of Science (digestion and absorption, development of the gastrointestinal tract in neonates). The research activity was focused on solving the problems faced by animal production in Poland, but it also resulted in a considerable number of physiological findings of an international dimension, and initiated new research areas.

Animal Experimentation↗
PubMed2002

The electromechanical effects of pacing at different sites within the right atrium.

AIMS: To compare high right atrium (HRA) with right atrial appendage (RAA) pacing with respect to atrial electromechanical function. METHODS: Eleven patients undergoing elective electrophysiological studies were studied in order directly to compare atrial conduction acutely associated with HRA and RAA pacing. Twenty-five patients with chronically implanted, active fixation leads in the HRA were compared with an age and sex matched group of 25 patients with chronically implanted, passive fixation leads in the RAA. For both studies recordings were taken in sinus rhythm then repeated when paced. Measured time intervals were intra- and interatrial activation times. P wave duration and time to onset of atrial systolic blood flow. RESULTS: Right atrial pacing, when compared with sinus rhythm, significantly prolongs the interatrial activation time, the P wave duration and the time to onset of right and left atrial blood flow irrespective of site paced. Comparing the RAA group with the HRA group, there were no statistical differences for any of the measured parameters. CONCLUSION: High right atrial free wall or the right atrial appendage pacing, when compared with sinus rhythm, is significantly detrimental to atrial electromechanical function. There is, however, no demonstrable difference between the two sites.

Adult↗
PubMed2002

Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains.

Virulence and immunity are poorly understood in Mycobacterium tuberculosis. We sequenced the complete genome of the M. tuberculosis clinical strain CDC1551 and performed a whole-genome comparison with the laboratory strain H37Rv in order to identify polymorphic sequences with potential relevance to disease pathogenesis, immunity, and evolution. We found large-sequence and single-nucleotide polymorphisms in numerous genes. Polymorphic loci included a phospholipase C, a membrane lipoprotein, members of an adenylate cyclase gene family, and members of the PE/PPE gene family, some of which have been implicated in virulence or the host immune response. Several gene families, including the PE/PPE gene family, also had significantly higher synonymous and nonsynonymous substitution frequencies compared to the genome as a whole. We tested a large sample of M. tuberculosis clinical isolates for a subset of the large-sequence and single-nucleotide polymorphisms and found widespread genetic variability at many of these loci. We performed phylogenetic and epidemiological analysis to investigate the evolutionary relationships among isolates and the origins of specific polymorphic loci. A number of these polymorphisms appear to have occurred multiple times as independent events, suggesting that these changes may be under selective pressure. Together, these results demonstrate that polymorphisms among M. tuberculosis strains are more extensive than initially anticipated, and genetic variation may have an important role in disease pathogenesis and immunity.

Bacterial Proteins↗
PubMed2002

Evaluation of the Directigen FluA+B test for rapid diagnosis of influenza virus type A and B infections.

Directigen FluA+B (BD Diagnostic Systems, Sparks, Md.), a new rapid test for the detection of influenza virus types A and B, was evaluated with nasopharyngeal aspirate specimens collected from 250 patients in comparison with culture and direct fluorescent antigen (DFA) detection tests. The patients studied were predominantly children, 80% being </=6 years old. Specimens negative by culture but positive by the Directigen FluA+B or DFA tests were analyzed by reverse transcription-PCR to resolve the discrepant results. The resolved sensitivity, specificity, and positive and negative predictive values of the Directigen FluA+B test for influenza virus type A were 96%, 99.6%, 96%, and 99.6%, respectively, and for influenza virus type B they were 87.5%, 96.8%, 80%, and 98%, respectively. Storage of nasopharyngeal aspirates in virus transport medium at 2 to 8 degrees C for 48 h had little adverse effect on the detection of influenza virus type A, but diagnosis of influenza virus type B is best carried out with fresh specimens. The test detected a range of human and animal influenza virus A subtypes, including the H5N1 and H9N2 viruses that recently caused human disease in Hong Kong.

Diagnosis, Differential↗
PubMed2002

Review of a pilot quality-assessment program for interpretative comments.

BACKGROUND: Interpretative commenting constitutes an important aspect of the post-analytical phase in chemical pathology, but has only recently been the subject of quality assessment. The Royal College of Pathologists of Australasia (RCPA)-Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program is currently in its third year, having started in 2000 as a pilot program. We present a review of the pilot program. METHODS: The program is aimed at individuals rather than laboratories. Two cases were circulated to participants of the Chemical Pathology Quality Assurance Program every month over a 6-month period. The case report contained the age and sex of the patient, together with brief clinical notes, the biochemistry results for commenting and other information of relevance. Three lines of space were given for the comment. The comments received from participants were broken down into their components and translated into common key phrases for the purpose of summarization and analysis. A histogram of the frequency of use of the common key phrases was generated. The comments or the key phrases were not given scores or marks, nor was any other indication given as to the appropriateness of their comments. RESULTS: This approach of simple peer-group comparison of comments without any assessment of the appropriateness of the comments was found to be inadequate; thus, when the program continues, key phrases will be classified according to degree of appropriateness and a suggested comment for each case will be proposed by an 'expert' panel. CONCLUSIONS: The program can serve a useful role in continuing education. Clinical biochemists and trainees who add interpretative comments to results produced by their laboratory, or give interpretative advice over the telephone, may potentially benefit from participating in this program.

Aged↗
PubMed2002

The value of permanent follow-up of implantable pacemakers--first results of an European trial.

A clinical study investigates the use of Home Monitoring (HM) in pacemaker therapy. For 3 months patients are supervised by daily automatic HM messages. Endpoints are the technical feasibility and the clinical benefit of HM. Ninety three patients have currently been included and followed for 72 +/- 30 days. Three patients were excluded due to insufficient mobile net coverage at their living sites. For the other patients, 5311 of 5911 messages were successfully registered. Interrupts in the sequence of messages occurred 331 times. Two hundred ten of these (63%) lasted just 1 day, 14 interrupts (4%) lasted 5 or more days. Two patients did not show any interrupts, 34 patients (38%) had interrupts of 3 and more days. The clinical benefit of Home Monitoring was found in the remote detection of arrhythmia and lead dislocation.

Adult↗
PubMed2002

Viagra on the internet: unsafe sexual practice.

The vast majority of men who experience some form of erectile dysfunction (ED) do not seek medical advice, mainly due to embarrassment and social stigma. They often prefer to seek unorthodox and covert methods of treatment. Unprescribed medication for ED is dangerous because of the strong association between ED and coronary heart disease. Published guidelines already exist for the management of patients presenting with sexual dysfunction and cardiovascular risks. In this case report we highlight that ED itself is a risk factor for occult CHD and illustrate the need for careful medical assessment and adherence to published guidelines for the management of ED.

Adult↗
PubMed2002

Susceptibility of young offenders to measles and rubella: an antibody prevalence study using oral fluid samples.

Three hundred and two oral fluid samples collected in January 2001 from male young offenders aged 18 to 21 years at HMP Hindley were screened for measles and rubella specific IgG, using 'in-house' amplified ELISA assays. MMR (measles/mumps/rubella) vaccine, offered at the same time, was accepted by 68.1% of the prisoners (92.7% of those agreeing to oral fluid antibody testing). Antibody prevalences were 92.1% for rubella and 80.8% for measles. This may, however, underestimate true prevalence as the sensitivity of the oral fluid assays used may be relatively poor in adults. Susceptibility levels are theoretically high enough to result in outbreaks should either infection enter this closed institutional environment. Since a measles outbreak would carry significant morbidity and rubella would represent a risk to associated non-immune women of childbearing age, it is suggested that prison health services should offer MMR to young offenders on entry.

Adolescent↗
PubMed2002

Investigation of prevalence of MRSA in referrals to neurosurgery: implications for antibiotic prophylaxis.

In order to establish the appropriateness of our current prophylactic antibiotic regimen we analysed the prevalence of MRSA in emergency referrals to our unit. MRSA screening records for all emergency admissions for a 3-month period were analysed. One-hundred-and-seventy-five patients were admitted as transfers from another hospital. Evidence of screening was found in 61% (107 patients). Of the screened patients, 15% (16) were MRSA positive. Source of referral or length of inpatient stay after referral to the time of transfer were not predictive for MRSA status. Gentamicin is active against more than 95% of MRSA strains cultured in our hospital and against 87% of MRSA strains cultured in the neurosurgery unit. A number-needed-to-treat (NNT) analysis showed that, with MRSA prevalence at 15%, cefuroxime plus gentamicin at induction could prevent one MRSA infection per 421 treated patients compared with cefuroxime alone. Vancomycin had minimal additional benefit over cefuroxime plus gentamicin (NNT: 1684). We conclude that MRSA carriage is common in patients referred as emergencies from other hospitals. Cefuroxime plus gentamicin can be used as antibiotic prophylaxis in this group. Vancomycin can be reserved for patients known to be colonized with MRSA (NNT: 51).

Adult↗