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Biomedical subjects

M Hannan

Publications and source records attributed to M Hannan.

At least 19 recordsLinked to original sources
PubMed2006

Molecular epidemiologic investigation of tuberculosis in an area of increasing incidence in inner-city Dublin.

In 2002 the tuberculosis (TB) incidence in Dublin was 13.1 cases per 100,000 persons. In inner city Dublin, the TB incidence was > 20 per 100,000 persons. TB notification rates have remained elevated. The objective of the study is to characterize the population affected in this inner city area and to investigate transmission patterns and potential risk factors for TB disease. This hospital-based molecular epidemiologic study included all culture positive cases of TB between January 1, 1998 and December 31, 2002 from the Mater Misericordiae University Hospital. 142 cases were analyzed. 84 (59%) had clustered Mycobacterium tuberculosis (Mtb) isolates, 58 (41%) had unique isolates by molecular typing. There were 13 clusters; the largest two clusters had 26 cases each, one linked to pubs, the other linked through family contact. In multivariate logistic regression analysis, birth in Ireland, pulmonary TB, and younger age were significantly associated with recent transmission. Dublin is a developed city with persistent areas of high rates of TB in the native population. Despite a functioning public health system and lack of predisposing risk factors such as HIV, immigration, and extreme poverty, TB can persist in pockets of the younger, native population.

Adolescent↗
PubMed2005

Voriconazole in the treatment of fungal osteomyelitis of the orbit in the immunocompromised host.

Scedosporium apiospermum is an uncommon cause of fungal infection in the orbit and sinus. Morbidity and mortality rates in immunocompromised patients are high. We review the first case of Scedosporium apiospermum orbito-sinus infection that was successfully treated with the new antifungal agent voriconazole. We highlight the efficacy of this drug, particularly in the treatment of osteomyelitis of the orbit and sinus, which may lead to an improvement in survival rates after Scedosporium infection.

Adult↗
PubMed2003

Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys.

Using a clinically relevant regimen, this study investigated the effects of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on bone loss, biochemical markers of bone turnover, densitometry, histomorphometry, biomechanical properties, and bone concentration in aged ovariectomized monkeys. Sixty-six female cynomolgus monkeys, aged 9 years and older, were ovariectomized (OVX) or sham operated. Intravenous (iv) bolus injections of ibandronate at 10, 30, or 150 microg/kg or placebo were administered at 30-day intervals (corresponding to intervals of 3 months in humans), starting at OVX, for 16 months. OVX significantly decreased bone mass at the lumbar spine, proximal femur, femoral neck, and radius and increased bone turnover in a time-dependent manner, as assessed by dual energy X-ray absorptiometry, peripheral quantitative computed tomography, or histomorphometry. Ibandronate iv bolus injections administered at 30 microg/kg every 30 days prevented osteopenia induced by estrogen depletion. OVX-induced increases in bone turnover (as determined by activation frequency, bone formation rate, and biochemical markers of bone turnover, including urinary N-telopeptide and deoxypyridinoline excretion and serum values for osteocalcin and bone-specific alkaline phosphatase) were suppressed on treatment, and bone mass, architecture, and strength were preserved at clinically relevant sites. Treatment with high-dose (150 microg/kg/dose) iv bolus injections of ibandronate further increased bone mass and improved bone strength at both the spine and femoral neck, without adversely affecting bone quality. In contrast, treatment with a 10 microg/kg/dose only partially prevented the OVX-induced effects. These data support the potential for the long-term administration of ibandronate by intermittent iv bolus injections in humans to prevent osteoporosis and improve bone quality at clinically relevant sites.

Animals↗
PubMed2001

Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality.

BACKGROUND: The impact of abdominal arterial calcific deposits on the prediction of cardiovascular disease (CVD) over a long follow-up interval deserves greater scrutiny. METHODS AND RESULTS: Lateral lumbar radiographs were studied as a predictor of incident coronary heart disease (CHD), CVD, and CVD mortality in 1049 men and 1466 women (mean age, 61 years) who were followed from 1967 to 1989. Anterior and posterior wall calcific deposits in the aorta at the level of the first through fourth lumbar vertebrae were graded according to increasing severity using a previously validated rating scale for abdominal aortic calcium (AAC) that ranges from 0 to 24 points. There were 454 cases of CHD, 709 cases of CVD, and 365 CVD deaths. Proportional hazards logistic regression was used to test for associations between AAC and later events after adjustment for age, cigarette use, diabetes mellitus, systolic blood pressure, left ventricular hypertrophy, body mass index, cholesterol, and HDL cholesterol. In comparisons with the lowest AAC tertile, the multivariate age-adjusted relative risks (RR) for CVD were increased in tertile 2 (men: RR, 1.33; 95% confidence interval [CI], 1.02 to 1.74; women: RR, 1.25; 95% CI, 0.95 to 1.65) and tertile 3 (men: RR, 1.68; 95% CI, 1.25 to 2.27; women: RR, 1.78; 95% CI, 1.33 to 2.38). Similar results were obtained with CHD and CVD mortality. CONCLUSIONS: AAC deposits, detected by lateral lumbar radiograms, are a marker of subclinical atherosclerotic disease and an independent predictor of subsequent vascular morbidity and mortality.

Aorta, Abdominal↗
PubMed2000

Central venous blood culture: a useful test for catheter colonisation?

OBJECTIVE: To evaluate the widespread practice of using qualitative culture of venous blood taken through central venous catheters (CVCs) as a means of diagnosing catheter colonisation in situ. DESIGN: A prospective clinical study. PATIENTS: Three hundred fifty-one CVCs were inserted into 228 critically ill patients. INTERVENTIONS: Prior to CVC removal, blood was taken for qualitative culture from the CVC and a peripheral site. All catheter tips underwent semi-quantitative analysis of bacterial colony count [1]. MEASUREMENTS AND RESULTS: One hundred eighteen (33.6%) CVCs were found to be colonised on removal. A positive central blood culture had a sensitivity and specificity of 50.8% and 78.9% when compared with the 'gold standard' of catheter tip culture. This gives a positive predictive value of 47.7% and a negative predictive value of 76.5%. The sensitivity and specificity of a positive peripheral blood culture were 41.5% and 77.7% with positive and negative predictive values of 48.8% and 72.9%, respectively. When only those catheters removed because of systemic sepsis (n = 139) were considered, a positive central blood culture had a sensitivity of 58.8% and a specificity of 69.3%. CONCLUSION: Our results indicate that the use of central blood culture confers a small advantage in sensitivity compared with peripheral blood culture. This advantage was further improved by only considering the catheters removed because of systemic sepsis but at the cost of a loss of specificity. Qualitative blood culture is a poor tool for the diagnosis of in-situ CVC colonisation.

Adult↗
PubMed2000

HIV associated culture proved tuberculosis has increased in north central London from 1990 to 1996.

OBJECTIVES: To examine rates of culture proved tuberculosis in HIV infected patients in three specialist centres in north central London. METHODS: Cases of tuberculosis in patients with previously documented HIV infection from 1990 to 1996 were identified retrospectively from microbiological/clinical records at Chelsea and Westminster, St Mary's, and University College London Hospitals. RESULTS: Between 1990 and 1996 202 cases of culture proved tuberculosis were identified at the three centres. Of these, 132/202 (65.3%) occurred in homosexual/bisexual men, 41/202 (20.3%) were in patients with heterosexual contact in sub-Saharan Africa, and 29/202 (14.4%) were in "others." Overall 148/202 (73.3%) had pulmonary tuberculosis. The total number of HIV infected individuals seen at the three centres increased from 4298 in 1990 to 5048 in 1996. Rates of tuberculosis in the three centres increased from 0.46% in 1990 to 0.83% in 1996. Part of this increase was due to an increase in tuberculosis among Africans from 1993 to 1996. CONCLUSIONS: Rates of HIV associated tuberculosis increased in these three centres in north central London between 1990 and 1996. In part this was due to an increase in the number of African patients with HIV infection attending the three centres. In addition, there was circumstantial evidence of recent transmission among homosexual men with HIV infection. Prospective "real time" surveillance of tuberculosis in HIV infected patients is needed in order to detect case clustering and to improve tuberculosis control.

Africa↗
PubMed1999

Antiseptic-bonded central venous catheters and bacterial colonisation.

This study was undertaken to evaluate the impact of chlorhexidine/silver sulphadiazine-bonded catheters on the incidence of colonisation and catheter-related sepsis in critically ill patients. Threehundred and fifty-one catheters were inserted into 228 patients during the study period, 174chlorhexidine/silver sulphadiazine-bonded catheters and 177 standard catheters. Indications for catheter removal were: death, clinical redundancy and clinical evidence of local or systemic infection. All catheter tips were sent to the microbiology laboratory for semiquantitative analysis of bacterial colony count. Seventy-one (40.2%) of the standard catheters and 47 (27.2%) of the antiseptic-bonded catheters were found to be colonised on removal (p < 0.01). Eight cases (4.7%) of catheter-related sepsis were associated with standard catheters and three cases (1.7%) with antiseptic-bonded catheters, however, this reduction was not statistically significant. Our results indicate that the use of antiseptic-bonded catheters in critically ill patients significantly reduces the incidence of bacterial colonisation.

Adult↗
PubMed1997

Association of insulin-like growth factor-I with body composition, weight history, and past health behaviors in the very old: the Framingham Heart Study.

OBJECTIVES: We examined correlates of insulin-like growth factor-I (IGF-I), an indicator of growth hormone levels, to identify factors associated with higher levels of IGF-I in old age. DESIGN: Nested study of cross-sectional correlates and early-life predictors of IGF-I level. SETTING: A longitudinal cohort study, the Framingham Heart Study. PARTICIPANTS: A total of 790 men and women (mean age 78.5, range 72-94), who had weight, waist and hip circumferences measured at the time of IGF-I measurement. MEASUREMENTS: Association of IGF-I with weight, fat distribution, functional status, nutritional indicators, and past health behaviors was assessed. We also examined IGF-I in relation to body composition derived from dual energy X-ray absorptiometry. RESULTS: IGF-I levels declined with age in both men and women. However, low IGF-I did not show expected associations with low lean mass and increased body fat. Current functional status and grip strength were not associated with IGF-I Low IGF-I was associated with weight loss in men; the strongest associations were with indicators of poorer nutritional status in both men and women. Levels of IGF-I in old age did not vary by past health behaviors. CONCLUSION: Although IGF-I declined with age, these data from the Framingham Heart Study did not show expected cross-sectional associations of weight, body fat, and lean mass. The strongest associations were between IGF-I and nutritional indicators. These results suggest caution may be warranted with regard to use of IGF-I as an indicator of growth hormone.

Aged↗
PubMed1997

Nasopharyngeal flora in HIV seropositive men who have sex with men.

OBJECTIVES: To assess, in men who were infected with the human immunodeficiency virus (HIV) and who identified themselves as having had sex with men; the nasopharyngeal prevalence of Neisseria gonorrhoeae, N meningitidis, Corynebacterium diphtheriae, and candida species; oral sexual behaviour; the relation between oral flora and oral sexual behavior. METHOD: Nasopharyngeal swabs were taken from HIV seropositive men for culture. The men were also asked to complete a self administered questionnaire. RESULTS: 390 men were recruited; 286 (73.3%) provided nasopharyngeal samples and questionnaires; 41 (10.5%) provided nasopharyngeal samples only; 63 (16.2%) provided questionnaires only. From the 327 nasopharyngeal samples N meningitidis was cultured in 49 (15%) and candida species in 165 (50.5%). Cultures for N gonorrhoeae and C diphtheriae were all negative. Data from the 349 completed questionnaires indicated that 285 men were practising oro-penile sex, over 90% did not consistently use condoms; 150 men were practising oro-anal sex, one used dental dams. In those providing both nasopharyngeal samples and sexual behaviour data meningococcal carriage was identified in 40 (17.5%) of the 228 men practising receptive oro-penile sex, compared with one (2.3%) of the 43 non-practisers (p < 0.025); in 21 (20%) of the 105 men practising insertive oro-anal sex, compared with 17 (12.5%) of the 136 non-practisers (p = 0.12). No correlation was identified between yeast carriage and oro-genital sex. CONCLUSION: Oro-genital sex, usually without barrier protection, is common among HIV infected men who have sex with men. It appears to be associated with increased meningococcal carriage but is autonomous to candida species isolation. Routine screening for nasopharyngeal N gonorrhoeae is not deemed necessary.

Candida↗
PubMed1996

Are risk factors for patellofemoral and tibiofemoral knee osteoarthritis different?

OBJECTIVE: To determine whether patellofemoral (PF), tibiofemoral (TF), and combined patterns of knee osteoarthritis (OA) differ in their strengths of associations with any of the known risk factors for knee OA, and especially to evaluate whether body mass index (BMI) correlates with all 3 patterns, or only with tibiofemoral disease, as previously suggested. METHODS: We obtained anteroposterior and lateral knee radiographs on 608 participants at the 22nd biennial examination of the Framingham cohort study (1992-3). The presence or absence of OA in the TF and PF compartments of each knee was scored, and subjects were classified on the basis of the pattern of compartmental involvement in their 2 knees. The strength of association of age, sex, BMI, chondrocalcinosis, and knee injury was computed for PF, TF, and combined pattern of knee OA using multiple logistic regression. RESULTS: The mean age and BMI of the sample were 80.7 yrs (SD 5.0) and 25.4.kg-2 (SD 3.7), respectively. PF, TF, and combined patterns of knee OA were present in 5.3, 23.0 and 19.7%, respectively. Elevated BMI was a risk factor for all 3 patterns of disease (adjusted OR for highest vs lowest tertile of BMI 3.7, 1.9, and 7.0 for PF, TF, and combined pattern, respectively). Risk factor profiles were broadly similar for TF and PF OA, with the possible exception of knee injury in men (adjusted OR = 2.0 for PF, 3.7 for TF OA). Risk factors were generally more strongly associated with the combined pattern of OA. CONCLUSION: Obesity is an important risk factor for PF, TF, and combined patterns of knee OA. The relationships of these patterns with the risk factors investigated here appear similar and are strongest for the combined pattern.

Aged↗
PubMed1994

A molecular study of EBV DNA and p53 mutations in nasopharyngeal carcinoma of Saudi Arab patients.

Tumor biopsies obtained from 25 Saudi Arab patients with nasopharyngeal carcinoma (NPC) were examined for the presence of Epstein-Barr virus (EBV) DNA detected by the polymerase chain reaction (PCR) and for the incidence of p53 mutations screened by a combination of PCR, single strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (PCR-RFLP). DNA sequencing was carried out to confirm the occurrence of p53 mutation. While 92% of the tumor specimens were found to carry EBV DNA, only 1/25 showed the incidence of a homozygous mutation at codon 248 of the p53 gene. The data showed that despite a high association of EBV infection with Saudi NPC, the frequency of p53 mutations was very low. Our results are consistent with the worldwide observation of infrequent p53 mutations in NPC.

Base Sequence↗
PubMed1994

Reduced induction of P53 protein by gamma-irradiation in ataxia telangiectasia cells without constitutional mutations in exons 5, 6, 7, and 8 of the p53 gene.

Ataxia telangiectasia (AT) is an autosomal recessive disease of childhood with several phenotypic characteristics. One of the hallmarks of this syndrome is its hypersensitivity to ionizing radiation, which is believed to be due to defects in DNA repair/processing. In addition to radio-resistant DNA synthesis, both fibroblasts and lymphoblastoid cell lines derived from these patients have been shown to have an impaired G1 arrest and prolonged G2 accumulation of cells indicating a defect in the regulation of cell cycle after irradiation. Since the (tumor suppressor) p53 protein has been reported to participate in the regulation of G1 arrest after irradiation, the possibility of p53 gene mutation and deregulating cell cycle in AT needed to be examined. We used the PCR amplification and DNA sequencing methods to detect mutations in the hypermutable exons (5-8) of germline p53 in fibroblast cells from 3 AT homozygotes. No mutation was found in any of these exons. In order to determine the role of the p53 protein in G1 arrest, its levels were measured before and after gamma-irradiation by flow cytometry in both AT and normal cells. Radiation-induced p53 protein levels in the AT cells varied from 6 to 60% compared to the normal cells, indicating a reduced induction of the protein in AT. These results suggest that mutation in the AT gene affects the p53 induction by irradiation and may, thus, alter the cell cycle regulation in the AT patients.

Ataxia Telangiectasia↗
PubMed1993

A comparison of antimicrobial sensitivities of urinary pathogens for the years 1980 and 1990.

Urinary tract infection is a major cause of morbidity in both the hospital and community which often requires empirical therapy. We have retrospectively studied laboratory diagnosed urinary tract infections for the years 1980 and 1990 to document the common pathogens and antimicrobial susceptibility patterns. In 1990 a significantly lower proportion of specimens yielded Proteus sp. or Klebsiella sp. than was the case in 1980. This was true of specimens from both the hospital and the community. There was an increase in the proportion of specimens yielding Pseudomonas sp. and coagulase negative Staphylococci (CNS). Significant changes in the antimicrobial susceptibility of urinary pathogens are also noted. In particular a greater proportion of isolates from the community were sensitive to cephalothin in 1990, while fewer isolates were sensitive to nalidixic acid and gentamicin. A greater proportion of isolated from hospital practice were sensitive to ampicillin, to cephalothin and to trimethoprim in 1990 while fewer isolates were sensitive to gentamicin. In relation to nitrofurantoin no significant change was noted. In respect of isolates from both community and hospital practice the agents ofloxacin, co-amoxiclav (not available in 1980) and gentamicin are those which are most consistently active.

Anti-Bacterial Agents↗
PubMed1991

Observations and an interpretation of dose-response relationships for cellular transformation in terms of induced (T) repair.

Both radiation-induced lethality and transformation frequency have been observed to plateau or diminish abruptly at relatively low dose levels and then increase with increasing doses, but at a reduced incremental rate. Discontinuities in dose-response relationships are postulated to correspond to the induction of a repair system ('T' repair) not functional at lower doses, i.e. below the induction threshold dose (Tt). Anomalies (discontinuities) in dose-response relationships and effects of dose fractionation previously noted are qualitatively explained in terms of this model.

Animals↗