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Biomedical subjects

M Meehan

Publications and source records attributed to M Meehan.

At least 19 recordsLinked to original sources
PubMed2002

International differences in ageing and spinal cord injury.

DESIGN: The present study is part of a programme of longitudinal research on ageing and spinal cord injury involving three populations - American, British and Canadian. The design was multivariate. OBJECTIVE: To identify international differences in outcomes associated with ageing and spinal cord injury. SETTING: A sample of 352 participants was assembled from five large, well-established databases. The Canadian sample was derived from the member database of the Canadian Paraplegic Association (Ontario and Manitoba divisions). The British sample was recruited from Southport Hospital's Northwest Regional Spinal Injuries Centre and Stoke-Mandeville Hospital's National Spinal Injuries Centre. The American sample has been recruited through Craig Hospital in Denver, Colorado. METHODS: The sample included individuals who had incurred a spinal cord injury at least 20 years previously; were admitted to rehabilitation within 1 year of injury; were between age 15 and 55 at the time of injury. Data were collected using a combination of self-completed questionnaires and interviews. Data included medical information, general health, hospitalisations, and changes in bladder and bowel management, equipment, pain, spasticity, the need for assistance, and other health issues. RESULTS: Clear international differences existed between the three samples in the three different countries. After controlling for sampling differences (ie, differences in age, level of lesion, duration of disability, etc.), the following differences were seen: (1) American participants had a better psychological profile and fewer health and disability-related problems; (2) British participants had less joint pain and less likelihood of perceiving they were ageing more quickly; (3) Canadians had more health and disability-related complications (particularly bowel, pain and fatigue problems). CONCLUSION: These differences are discussed in terms of socio-political, health care system and cultural factors that might be used to explain them, and to generate hypotheses for future research.

Adult↗
PubMed2001

Evaluation of the chemotherapy patient monitor: an interactive tool for facilitating communication between patients and oncologists during the cancer consultation.

Effective communication between oncologists and patients with cancer is of paramount importance. The Chemotherapy Patient Monitor (CPM) is a novel tool designed to assist doctor-patient communication regarding patient concerns and side-effects. Initially, the CPM was assessed in a primary evaluation study of its use during consultations with 26 patients with advanced colorectal cancer (one consultation without, followed by two with, the CPM per patient). This led to a further dissemination/audit of 34 patients attending oncology centres in the UK, who had completed the survey prior to three consultations. The CPM contains a checklist of common side-effects of chemotherapy regimens used in advanced colorectal cancer, and other common concerns of patients with advanced colorectal cancer. The CPM records the presence of side-effects/concerns, the distress caused, whether patients wish to discuss them further, and actions taken as a result. Questionnaires explored the views of patients and oncologists in the UK and Spain regarding the effectiveness of consultations during a baseline visit conducted without the CPM, and then with the CPM in subsequent visits. These data were then complemented by the dissemination/audit study of the CPM across nine centres in the UK. All patients understood the CPM. The CPM was rated as useful by oncologists in 83% of consultations, and did not lengthen 82% of visits. Patients felt it had improved the visit in 95% of cases. Responses from patients (100%) and oncologists (84%) indicated willingness to use the CPM for at least some consultations in the future. The results of the dissemination/audit study supported these conclusions. We conclude that the CPM appears to be a useful new tool for improving patient-doctor communication during cancer consultations.

Antineoplastic Agents↗
PubMed2001

Randomized trial of presumptive sexually transmitted disease therapy during pregnancy in Rakai, Uganda.

OBJECTIVE: The purpose of this study was to assess presumptive sexually transmitted disease treatment on pregnancy outcome and HIV transmission. STUDY DESIGN: In a randomized trial in Rakai District, Uganda, 2070 pregnant women received presumptive sexually transmitted disease treatment 1 time during pregnancy at varying gestations, and 1963 control mothers received iron/folate and referral for syphilis. Maternal-infant sexually transmitted disease/HIV and infant outcomes were assessed. Intent-to-treat analyses estimated adjusted rate ratios and 95% confidence intervals. RESULTS: Sexually transmitted diseases were reduced: Trichomonas vaginalis (rate ratio, 0.28; 95% CI, 0.18%-0.49%), bacterial vaginosis (rate ratio, 0.78; 95% CI, 0.69-0.87), Neisseria gonorrhoeae /Chlamydia trachomatis (rate ratio, 0.43; 95% CI, 0.27-0.68), and infant ophthalmia (rate ratio, 0.37; 95% CI, 0.20-0.70). There were reduced rates of neonatal death (rate ratio, 0.83; 95% CI, 0.71-0.97), low birth weight (rate ratio, 0.68; 95% CI, 0.53-0.86), and preterm delivery (rate ratio, 0.77; 95% CI, 0.56-1.05); but there were no effects on maternal HIV acquisition or perinatal HIV transmission. CONCLUSION: Reductions of maternal sexually transmitted disease improved pregnancy outcome but not maternal HIV acquisition or perinatal HIV transmission.

Azithromycin↗
PubMed2001

The fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi additionally binds IgG and contributes to virulence in a mouse model.

The major cell-wall-associated protein of the equine pathogen Streptococcus equi subsp. equi is an M-like fibrinogen-binding protein (FgBP) which binds equine fibrinogen (Fg) avidly, through residues located at the extreme N-terminus of the molecule. In this study, it is shown that FgBP additionally binds equine IgG-Fc. When tested against polyclonal IgG from ten other animal species, it was found that FgBP binds human, rabbit, pig and cat IgG, but does not bind mouse, rat, goat, sheep, cow or chicken IgG. Through the use of a panel of recombinant FgBP truncates containing defined deletions of sequence, it was shown that residues in the central regions of FgBP are important in IgG binding. An fbp knockout mutant which does not express FgBP on the cell surface was also constructed. Mutant cells failed to autoaggregate, bound no detectable equine Fg or IgG-Fc, were rapidly killed in horse blood, and showed greatly decreased virulence in a mouse model. Results suggest that FgBP is the major surface structure responsible for binding either Fg or IgG, that the molecule has pronounced antiphagocytic properties, and that it is a likely factor contributing to the virulence of wild-type S. equi subsp. equi.

Animals↗
PubMed2000

Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. Rakai Project Team.

BACKGROUND: Male circumcision is associated with reduced HIV acquisition. METHODS: HIV acquisition was determined in a cohort of 5507 HIV-negative Ugandan men, and in 187 HIV-negative men in discordant relationships. Transmission was determined in 223 HIV-positive men with HIV-negative partners. HIV incidence per 100 person years (py) and adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated by Poisson regression. HIV-1 serum viral load was determined for the seropositive partners in HIV-discordant couples. RESULTS: The prevalence of circumcision was 16.5% for all men; 99.1% in Muslims and 3.7% in non-Muslims. Circumcision was significantly associated with reduced HIV acquisition in the cohort as a whole (RR 0.53, CI 0.33-0.87), but not among non-Muslim men. Prepubertal circumcision significantly reduced HIV acquisition (RR 0.49, CI 0.26-0.82), but postpubertal circumcision did not. In discordant couples with HIV-negative men, no serconversions occurred in 50 circumcised men, whereas HIV acquisition was 16.7 per 100 py in uncircumcised men (P = 0.004). In couples with HIV-positive men, HIV transmission was significantly reduced in circumcised men with HIV viral loads less than 50000 copies/ml (P = 0.02). INTERPRETATION: Prepubertal circumcision may reduce male HIV acquisition in a general population, but the protective effects are confounded by cultural and behavioral factors in Muslims. In discordant couples, circumcision reduces HIV acquisition and transmission. The assessment of circumcision for HIV prevention is complex and requires randomized trials.

Adolescent↗
PubMed2000

Neither the A- nor B-repeat regions of the fibrinogen-binding protein of Streptococcus equi subsp. equi are essential for fibrinogen binding.

The major cell wall-associated protein (FgBP) of Streptococcus equi subsp. equi possesses two internal blocks of repeated sequence (A and B) and binds horse fibrinogen (Fg) avidly through residues located in the N-terminal half of the molecule. In the present study, we investigated the roles of the two repeats blocks in Fg binding through construction of recombinant FgBP proteins containing defined internal deletions of sequence. Ligand binding experiments clearly showed that neither repeat is essential for Fg binding. However, residues within the B repeats seem to play a major role in the aberrant mobility observed for FgBP following sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Animals↗
PubMed2000

Minimally invasive surgical staging for esophageal cancer.

BACKGROUND: The incidence of esophageal adenocarcinoma is increasing in the United States, and the 5-year survival rate is dismal. Preliminary data suggest that conventional imaging is inaccurate in staging esophageal cancer and could limit accurate assessment of new treatments. The objective of this study was to compare minimally invasive surgical staging (MIS) with conventional imaging for staging esophageal cancer. METHODS: Patients with potentially resectable esophageal cancer were eligible. Staging by conventional methods used computed tomography (CT) scan of the chest and abdomen, and endoscopic ultrasound (EUS), whereas MIS used laparoscopy and videothoracoscopy. Conventional staging results were compared to those from MIS. RESULTS: In 53 patients, the following stages were assigned by CT scan and EUS: carcinoma in situ (CIS; n = 1), I (n = 1), II (n = 23), III (n = 20), IV (n = 8). In 17 patients (32.1%), MIS demonstrated inaccuracies in the conventional imaging, reassigning a lower stage in 10 patients and a more advanced stage in 7 patients. CONCLUSIONS: In 32.1% of patients with esophageal cancer, MIS changed the stage originally assigned by CT scan and EUS. Therefore, MIS should be applied to evaluate the accuracy of new noninvasive imaging methods and to assess new therapies for esophageal cancer.

Adenocarcinoma↗
PubMed2000

Whole-body FDG positron emission tomographic imaging for staging esophageal cancer comparison with computed tomography.

PURPOSE: The aim of the authors in this study was to critically evaluate the role of whole-body positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) in staging esophageal cancer, and further to compare this method with conventional imaging with computed tomography (CT). MATERIALS AND METHODS: The authors performed independent, blinded retrospective evaluations of FDG PET images obtained in 47 patients referred for the initial staging of esophageal cancer before minimally invasive surgical staging. Twenty PET studies from patients with nonesophageal thoracic cancers were randomly selected for inclusion in the PET readings. In a subset of 37 of 47 cases, the PET findings were compared with independent readings of CT studies acquired within the same 6-week interval. The utility of the imaging findings was evaluated using a high-sensitivity interpretation (i.e., assigning equivocal findings as positive) and a low-sensitivity interpretation (i.e., assigning equivocal findings as negative). RESULTS: PET was less sensitive (41% in high-sensitivity mode, 35% in low-sensitivity mode) than CT (63% to 87%) for diagnosing tumor involvement in locoregional lymph nodes, which was identified by surgical assessment in 72% of patients. Notable, however, was the greater specificity of PET-determined nodal sites (to approximately 90%) compared with CT (14% to 43%). In detecting histologically proved distant metastases (n = 10), PET performed considerably better when applied in the high-sensitivity mode, with a sensitivity rate of approximately 70% and a specificity rate of more than 90% in the total group and in the subset of patients with correlative CT data. In the low-sensitivity mode, CT identified only two of seven metastatic sites, whereas the high-sensitivity mode resulted in an unacceptably high rate of false-positive readings (positive predictive value, 29%). PET correctly identified one additional site of metastasis that was not detected by CT. CONCLUSIONS: The relatively low sensitivity of PET for identifying locoregional lesions precludes its replacement of conventional CT staging. However, the primary advantage of PET imaging is its superior specificity for tumor detection and improved diagnostic value for distant metastatic sites, features that may substantially affect patient management decisions. In conclusion, PET imaging is useful in the initial staging of esophageal cancer and provides additional and complementary information to that obtained by CT imaging.

Adenocarcinoma↗
PubMed2000

Beyond the pressure ulcer blame game: reflections for the future.

The concept of skin wounds caused primarily as a result of external physical forces has been the focus of many healthcare professionals for decades. Unfortunately, some of the choices made regarding the definition, description, and topical management of pressure ulcers hampers the appreciation of the complexity of issues that generally accompany the occurrence of these wounds. As the healthcare industry increasingly focuses on quality and accountability, industry watchdogs continue to develop metrics to evaluate quality of care while legal professionals demand more accountability for healthcare interventions. The management of pressure ulcers is often scrutinized and many healthcare providers are often unfairly accused of neglect. The occurrence of pressure ulcers, when viewed as a failure of the healthcare system, prevents the comprehensive and constructive attention this topic deserves. Therefore, as wound care providers, we must change the image of pressure ulcers and provide a more balanced portrayal of the influences, treatments, and likely outcomes of these wounds. We must separate fact from fiction and reality from the psychological reaction that pressure ulcers evoke. It is now time to recreate a dialogue for pressure ulcers that is productive, realistic, and likely to result in the advancement of care.

Attitude to Health↗
PubMed1999

The road to abortion (II): how government got hooked.

The first part of this series traced close links between eugenics (the effort to breed a "better" human race) and population control throughout the greater part of this century up to the 1960s. It stressed the population work of early eugenicists and eugenics sympathizers such as Frederick Osborn, Margaret Sanger, Gunnar Myrdal, Alan Guttmacher, Garrett Hardin and John D. Rockefeller 3rd. This second and concluding part will show how population controllers, from the 60s onward increasingly added economic and foreign-policy concerns to their original "eugenics" motive of improving human genetic stock. Working in both Democratic and Republican administrations, they gained major government backing for their programs and also played a key role in the legalization of abortion. I will use President Richard Nixon's administration as an example of heavy government involvement.

Abortion, Legal↗
PubMed1997

Antigen 43, a phase-variable bipartite outer membrane protein, determines colony morphology and autoaggregation in Escherichia coli K-12.

The product controlling colony form variation and autoaggregation in Escherichia coli K-12 (the flu gene product) has been identified as the phase-variable, bipartite, outer membrane protein, termed antigen 43 (Ag43). Identification is based: (i) on complete correlation in authentic flu variants between colony morphology/autoaggregation and Ag43 expression as determined by colony and Western immunoblotting and immunofluorescence microscopy; and (ii) on the use of a specific probe to map the gene encoding Ag43 to a position (min 43) on the E. coli chromosome previously established for flu.

Amino Acid Sequence↗
PubMed1997

A novel regulatory mechanism for a novel phase-variable outer membrane protein of Escherichia coli.

Antigen 43 (Ag43) is a prominent hetero-oligomeric protein complex in the outer membrane of Escherichia coli. It is composed of two subunits. alpha 43 (M(r) 60, 000) and beta 43 (M(r) 53, 000) in 1:1 stoichiometry. alpha 43 is surface expressed, extends beyond the O-side chains of smooth lipopolysaccharide and is bound to the cell surface through an interaction with beta 43, itself an integral outer membrane protein, alpha 43 shows limited sequence homology with some enterobacterial adhesins. Expression of Ag43 is subject to reversible phase variation, the rates of variation from the Ag43+ve to Ag43-ve states in liquid minimal medium being approximately 2.2 x 10(-3), the corresponding rates from Ag43-ve to Ag43+ve states being approximately 1 x 10(-3). Phase switching of genes encoding Ag43 are transcriptionally regulated by DNA methylation (deoxyadenosine methylase [dam] mutants being "locked OFF") and by OxyR (oxyR mutants being "locked ON"). It is proposed that OxyR acts as a repressor of Ag43 transcription by binding to unmethylated GATC sites in the regulatory region of the gene. Sequencing and mapping has identified Ag43 as the likely product of the metastable flu gene first described in 1980 by Diderichsen and responsible for colony form variation in E. coli.

Amino Acid Sequence↗
PubMed1997

Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL). RESULTS: The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained. CONCLUSION: The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.

Adenocarcinoma↗
PubMed1996

Phase-variable outer membrane proteins in Escherichia coli.

Escherichia coli contains at least two phase-variable proteins in its outer membrane. One, termed antigen 43 (Ag43), is the product of the metastable flu gene located at min 43.6 on the E. coli chromosome and is responsible for colony form variation and for autoaggregation in liquid media. Ag43 is composed of two proteinaceous subunits, alpha 43 and beta 43 in 1:1 stoichiometry. alpha 43 (apparent M(r) 60,000) is surface expressed, extends beyond the O-side chains of smooth lipopolysaccharide and is bound to the cell surface through an interaction with beta 43 (apparent M(r) 53,000), itself an integral, heat-modifiable, outer membrane protein. alpha 43 shows limited N-terminal sequence homology with certain enterobacterial adhesins, and notable sequence homology with AIDA-1, an adhesin of diffuse-adhering E. coli. In addition, alpha 43 contains an RGD motif and a consensus sequence for an (autoproteolytic?) aspartyl protease active site. Expression of Ag43 is subject to reversible phase variation-in liquid minimal medium, the rates of variation from Ag43+ to Ag43- states and from Ag43- to Ag43+ states being approximately 2.2 x 10(-3) and approximately 1 x 10(-3), respectively. Phase switching of Ag43 is regulated by DNA methylation (deoxyadenosine methylase (dam) mutants being 'locked OFF') and by OxyR (oxyR mutants being 'locked ON'). It is proposed that OxyR acts as a repressor of Ag43 transcription by binding to unmethylated GATC sites in the regulatory region of the gene. In some strains, Ag43 may also undergo antigenic variation. A 94 kDa immunocrossreactive outer membrane protein, showing similar rates of phase variation, has additionally been detected for some enteropathogenic and uropathogenic strains of E. coli. This 94 kDa protein can be proteolytically cleaved in situ with trypsin to yield two membrane-bound products with M(r)s and properties similar to those of alpha 43 and beta 43. Results suggest that Ag43 may represent one of a family of antigenically-related high-M(r) adhesins which are synthesized as polyprotein precursors. Some members may be processed and presented on the cell surface as bipartite protein complexes (as Ag43). Others can remain uncleaved.

Amino Acid Sequence↗