Search PubMed⌕ Search

Biomedical subjects

P Adams

Publications and source records attributed to P Adams.

At least 19 recordsLinked to original sources

Identification of putative ancestors of the multidrug-resistant Salmonella enterica serovar typhimurium DT104 clone harboring the Salmonella genomic island 1.

The origin of multidrug-resistant Salmonella enterica serovar typhimurium (S. typhimurium) harboring the Salmonella Genomic Island 1 (SGI1), which was detected for the first time in the mid-1980s is unknown. In this study, we performed microarray genomotyping of four multidrug-resistant SGI1 positive strains and found that unlike the S. typhimurium LT2 strain, the multidrug-resistant strains lacked genes STM0517-0529 allowing the utilization of allantoin as a sole nitrogen source. We extended this observation by PCR screening of additional 120 S. typhimurium field strains and found that this locus was absent in all SGI1 positive and also in 24% of SGI1 negative strains, which were proposed to be the original recipients of SGI1. To prove this hypothesis, we compared the STM0517-0529 negative strains (with or without the SGI1) by PFGE and PCR prophage typing and found that 8 out of 11 of the SGI1 negative strains and 17 out of 22 SGI1 positive strains were of identical PFGE pattern and PCR prophage pattern, while this specific pattern was never observed among STM0517-0529 positive strains. We therefore propose that a lineage of the S. typhimurium DT104 sensitive strain first lost the ability to metabolize allantoin and then acquired SGI1.

Anti-Bacterial Agents↗

Hepatitis B surface antigen presentation and HLA-DRB1*- lessons from twins and peptide binding studies.

The aim of this study was to investigate the underlying mechanisms of the genetic association between certain HLA-DRB1* alleles and the immune response to HBsAg vaccination. Therefore, HBsAg peptide binding to HLA-DR molecules was measured in vitro by peptide binding ELISAs. Additionally, HBsAg-specific T cell reaction and cytokine profile of immune response were analysed ex vivo in ELISPOT assays and DR-restriction of T-cell proliferative responses was investigated with HBsAg specific T cell clones. In addition, we compared HBsAg specific T cell responses of 24 monozygotic and 3 dizygotic twin pairs after HBsAg vaccination. Our results showed that the peptide binding assays did not reflect antigen presentation in vivo. DR alleles associated with vaccination failure like DRB1*0301 and 0701 efficiently presented HBsAg peptides. In 11 of 24 investigated monozygotic twin pairs we observed pronounced differences in the recognition of HBsAg peptides. This study indicates that HLA-DR associations with HBsAg vaccination response are not caused by differences in peptide binding or by a shift in the Th1/Th2 profile. Our findings strongly argue for differences in the T cell recognition of peptide/MHC complexes as the critical event in T cell responsiveness to HBsAg.

Adolescent↗

Source, dispersion and combustion modelling of an accidental release of hydrogen in an urban environment.

Hydrogen is likely to be the most important future energy carrier, for many stationary and mobile applications, with the potential to make significant reductions in greenhouse gas emissions especially if renewable primary energy sources are used to produce the hydrogen. A safe transition to the use of hydrogen by members of the general public requires that the safety issues associated with hydrogen applications have to be investigated and fully understood. In order to assess the risks associated with hydrogen applications, its behaviour in realistic accident scenarios has to be predicted, allowing mitigating measures to be developed where necessary. A key factor in this process is predicting the release, dispersion and combustion of hydrogen in appropriate scenarios. This paper illustrates an application of CFD methods to the simulation of an actual hydrogen explosion. The explosion occurred on 3 March 1983 in a built up area of central Stockholm, Sweden, after the accidental release of approximately 13.5 kg of hydrogen from a rack of 18 interconnected 50 l industrial pressure vessels (200 bar working pressure) being transported by a delivery truck. Modelling of the source term, dispersion and combustion were undertaken separately using three different numerical tools, due to the differences in physics and scales between the different phenomena. Results from the dispersion calculations together with the official accident report were used to identify a possible ignition source and estimate the time at which ignition could have occurred. Ignition was estimated to occur 10s after the start of the release, coinciding with the time at which the maximum flammable hydrogen mass and cloud volume were found to occur (4.5 kg and 600 m(3), respectively). The subsequent simulation of the combustion adopts initial conditions for mean flow and turbulence from the dispersion simulations, and calculates the development of a fireball. This provides physical values, e.g. maximum overpressure and far-field overpressure that may be used as a comparison with the known accident details to give an indication of the validity of the models. The simulation results are consistent with both the reported near-field damage to buildings and persons and with the far-field damage to windows. The work was undertaken as part of the European Integrated Hydrogen Project-Phase 2 (EIHP2) with partial funding from the European Commission via the Fifth Framework Programme.

Accidents↗

Small bowel incarceration in a broad ligament defect.

We report the case of a 33-year-old woman whose medical history included three normal pregnancies without previous abdominal or pelvic surgery. She presented with small bowel obstruction. An abdominal computed tomography (CT) scan study revealed air fluid levels in the pelvis. Laparoscopic exploration revealed a viable ileal loop incarcerated through the mesoligamentum teres. The intestinal loop was reduced and the broad ligament defect was closed with a laparoscopic absorbable clip. Among internal hernias, hernias through a defect in the broad ligament represent only 4-7%. Defects within the broad ligament can be either congenital (ruptured cystic structures reminiscent of the mesonephric or mullerian ducts) or secondary to operative trauma, pregnancy and birth trauma, or prior pelvic inflammatory disease. CT scan may be diagnostic by showing incarceration of a dilated intestinal loop in the Douglas pouch with air fluid levels. This is the first reputed case of a totally laparoscopic repair of a bowel incarceration through a broad ligament defect.

Abdominal Pain↗

Clinical protocol. Purging of autologous stem cell sources with bcl-x(s) adenovirus for women undergoing high-dose chemotherapy for stage IV breast carcinoma.

High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. However, the bone marrow of such patients is often contaminated with tumor cells. Recently, we have found that a recombinant adenovirus vector that contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family), called the bcl-x(s) adenovirus, is lethal to cancer cells derived from epithelial tissues, but not to normal human hematopoietic cells. To determine the mechanism, by which this virus spares normal hematopoietic cells, we isolated normal mouse hematopoietic stem cells and infected them with an adenovirus that contains a beta-galactosidase minigene. Such cells do not express beta-galactosidase, indicating that hematopoietic stem cells do not express transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT.

Adenoviridae↗

Proteomic detection of PhoPQ- and acid-mediated repression of Salmonella motility.

Salmonella adaptation to low pH is a critical survival response and essential for virulence. Here, we show that another key virulence-associated process, flagella-mediated cell motility, is co-regulated by low pH via the PhoPQ signal transduction system. Using a proteomic approach, we found that phase 1 and phase 2 flagellin were specifically down-regulated when acid-adapted (pH 5.0) Salmonella SL1344 cells were exposed to pH 3.0. Decreased flagellin expression and cell motility was dependent on activation of the PhoPQ pathway, which directly or indirectly negatively regulated transcription of the flagellin gene fliC. In contrast, the general stress sigma factor RpoS (sigma s) positively regulated flagellar gene expression. Low external pH had no effect on the level of H-NS protein, a further regulator of flagellar gene expression. We suggest that flagellar repression at low pH conserves ATP for survival processes and helps to limit the influx of protons into the cytosol. These results highlight the power of proteomics to reveal unanticipated links between relatively well-characterised regulatory systems in bacteria.

Adaptation, Physiological↗

Religiousness and substance use in children of opiate addicts.

PURPOSE: To investigate among children of opiate addicts a potential protective effect of religiousness (broadly defined in the literature to include religious beliefs, practice, and tradition) against onset of substance use. METHODS: Subjects were 161 opiate-addicted biological parents recruited from methadone maintenance programs in the New York metropolitan area, their 279 children, and 63 non-opiate-addicted parents with whom the child had daily contact. Childhood onset of substance use was assessed using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS); parental DSM-III-R diagnosis of opiate addiction was assessed using the SADS-Lifetime Version (SADS-L). RESULTS: Religiousness in children of opiate addicts was associated with a substantially decreased likelihood of onset of substance use. Parent-child concordance of religiousness showed additional protective qualities with respect to religious denomination in opiate-addicted parent and with respect to the personal importance of religion and frequent attendance of religious services in non-opiate-addicted parents. CONCLUSION: Religiousness protects against substance use among children of opiate addicts.

Adolescent↗

Allogeneic stem cell transplantation reduces disease progression compared to autologous transplantation in patients with multiple myeloma.

This study compares the probability of disease progression, progression-free survival, and overall survival between patients undergoing an allogeneic or autologous transplant for multiple myeloma using an identical preparative regimen. Patients received a preparative regimen of TBI, busulfan, and cyclophosphamide followed by an allogeneic or autologous transplant. In the allogeneic group (n = 21), six patients received bone marrow and 15 received G-CSF mobilized PBSC; all autologous patients (n = 35) received PBSC mobilized with cyclophosphamide and G-CSF. Allogeneic donors were HLA-identical (n = 20) or one-antigen mismatched (n = 1) siblings. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (n = 10), tacrolimus/methotrexate (n = 6), cyclosporine/methotrexate (n = 4), or cyclosporine (n = 1). The groups were evenly matched for gender, pretransplant therapy, disease status at time of transplant, myeloma subtype, and time from diagnosis to transplant. The median age was significantly lower in the allogeneic group (48 vs 55 years, P < 0.01). In the allogeneic group the probabilities of developing acute GVHD grade II-IV and chronic GVHD were 55% and 82%, respectively. The Kaplan-Meier probability of disease progression was significantly lower in the allogeneic group (11% vs 64%, P < 0.001) compared to the autologous group. Although progression-free (60% vs 30%, P = 0.19) and overall survival at 2 years (60% vs 42%, P = 0.39) favored the allogeneic group, this did not reach statistical significance. Within the allogeneic transplant group, patients age 50 years or under had a 3-year overall survival significantly higher when compared to older patients (79% vs 29%, P = 0.03). Using identical preparative regimens, allogeneic transplantation reduced disease progression compared to autologous transplantation for myeloma. This suggests that allogeneic transplantation induces a graft-versus-myeloma (GVM) effect.

Actuarial Analysis↗

A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B.

Seventy-seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty-seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7-48.5) in the transplanted patients and 26 months (range, 0.1-37) in the nontransplanted group. Twenty-five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow-up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV-DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV-DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine-treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.

Adult↗

Evidence-based guideline for the primary care management of stable angina.

This is an updated version of the first North of England Stable Angina Guideline (1,2) and summarizes the full guideline. (3) This paper presents all the recommendations within the guideline; and where these are new or substantially altered from the original version, it also presents a summary of the supporting evidence. The aims and methods of development (summarized in Box 1) of this guideline are unchanged from the original version, to which readers are directed for more detail. The research questions raised during the development of this guideline are shown in Box 2.

Angina Pectoris↗

Flagellar phase variation of Salmonella enterica serovar Typhimurium contributes to virulence in the murine typhoid infection model but does not influence Salmonella-induced enteropathogenesis.

Although Salmonella enterica serovar Typhimurium can undergo phase variation to alternately express two different types of flagellin subunit proteins, FljB or FliC, no biological function for this phenomenon has been described. In this investigation, we constructed phase-locked derivatives of S. enterica serovar Typhimurium that expressed only FljB (termed locked-ON) or FliC (termed locked-OFF). The role of phase variation in models of enteric and systemic pathogenesis was then evaluated. There were no differences between the wild-type parent strain and the two phase-locked derivatives in adherence and invasion of mouse epithelial cells in vitro, survival in mouse peritoneal macrophages, or in a bovine model of gastroenteritis. By contrast, the locked-OFF mutant was virulent in mice following oral or intravenous (i.v.) inoculation but the locked-ON mutant was attenuated. When these phase-locked mutants were compared in studies of i.v. kinetics in mice, similar numbers of the two strains were isolated from the blood and spleens of infected animals at 6 and 24 h. However, the locked-OFF mutant was recovered from the blood and spleens in significantly greater numbers than the locked-ON strain by day 2 of infection. By 5 days postinfection, a majority of the mice infected with the locked-OFF mutant had died compared with none of the mice infected with the locked-ON mutant. These results suggest that phase variation is not involved in the intestinal stage of infection but that once S. enterica serovar Typhimurium reaches the spleens of susceptible mice those organisms in the FliC phase can grow and/or survive better than those in the FljB phase. Additional experiments with wild-type S. enterica serovar Typhimurium, fully capable of switching flagellin type, supported this hypothesis. We conclude that organisms that have switched to the FliC(+) phase have a selective advantage in the mouse model of typhoid fever but have no such advantage in invasion of epithelial cells or the induction of enteropathogenesis.

Animals↗

Consensus statement on the live organ donor.

OBJECTIVE: To recommend practice guidelines for transplant physicians, primary care providers, health care planners, and all those who are concerned about the well-being of the live organ donor. PARTICIPANTS: An executive group representing the National Kidney Foundation, and the American Societies of Transplantation, Transplant Surgeons, and Nephrology formed a steering committee of 12 members to evaluate current practices of living donor transplantation of the kidney, pancreas, liver, intestine, and lung. The steering committee subsequently assembled more than 100 representatives of the transplant community (physicians, nurses, ethicists, psychologists, lawyers, scientists, social workers, transplant recipients, and living donors) at a national conference held June 1-2, 2000, in Kansas City, Mo. CONSENSUS PROCESS: Attendees participated in 7 assigned work groups. Three were organ specific (lung, liver, and kidney) and 4 were focused on social and ethical concerns (informed consent, donor source, psychosocial issues, and live organ donor registry). Work groups' deliberations were structured by a series of questions developed by the steering committee. Each work group presented its deliberations to an open plenary session of all attendees. This information was stored and shaped into a statement circulated electronically to all attendees for their comments, and finally approved by the steering committee for publication. The term consensus is not meant to convey universal agreement of the participants. The statement identifies issues of controversy; however, the wording of the entire statement is a consensus by approval of all attendees. CONCLUSION: The person who gives consent to be a live organ donor should be competent, willing to donate, free from coercion, medically and psychosocially suitable, fully informed of the risks and benefits as a donor, and fully informed of the risks, benefits, and alternative treatment available to the recipient. The benefits to both donor and recipient must outweigh the risks associated with the donation and transplantation of the living donor organ.

Health Status↗

Prevalence and genotypic characterisation of Giardia in dairy calves from Western Australia and Western Canada.

In this study, the prevalence of Giardia duodenalis infections was determined in Western Canadian and Western Australian dairy calves. Faecal samples were collected from Holstein calves located on a commercial dairy near Lethbridge, Alta., Canada (N=28) and from calves located on two commercial dairies located near Perth, WA, Australia (N=36). Faecal samples were examined for the presence of Giardia cysts using sucrose gradient centrifugation, followed by immunofluoresence microscopy. DNA was then extracted from Giardia isolates obtained from positive samples. A PCR based method was employed to amplify and sequence a 292bp region of the 16S-rRNA gene. Genetic sequences obtained from Giardia isolates were compared to each other and to previously sequenced isolates. Following a single faecal sample, 58% of Western Australian calves and 57% of Western Canadian calves were positive for Giardia. Geometric mean cyst counts/g of faeces were 839 for Western Australian calves and 3475 for Western Canadian calves, but these values did not differ significantly. Genetic sequences were obtained from 10 calves from Western Canada, while six sequences were obtained from Western Australian calves. Of the Western Canadian isolates, eight aligned with the proposed 'Hoofed livestock' genotype. Of the five isolates obtained from Western Australian calves, four sequences were identical to the 'Hoofed livestock' genotype. Two isolates from the Western Canadian calves and one isolate from the Western Australian calves had the identical genetic sequence to the Genotype (Assemblage) A sequence, a common human genotype. The results of this study demonstrate, for the first time, that Giardia infections occur in Western Australian calves. Also, calves from different geographical locations appear to be primarily infected with a Giardia genotype unique to hoofed livestock. However, calves can shed Giardia cysts potentially infective for humans. Thus, Giardia infections should be considered important to Australian dairy producers, and infections in calves may pose a risk to public health regardless of geographical location.

Animals↗

Problem gamblers: do GPs want to intervene?

AIM: To survey GPs' attitudes towards problem gamblers and knowledge to successfully intervene. METHODS: 100 GPs, randomly selected for gender and geographical distribution, were anonymously surveyed by questionnaire through the Royal New Zealand College of General Practitioners. RESULTS: 80 GPs responded (80% of those surveyed). There was strong support (85%) for problem gambling being within a GP's mandate, for involvement in treatment of problem gambling (72%) and for their having a role in supporting a family where a member has a gambling problem (80%). There was less confidence in: raising the issue of gambling with patients (53%), in knowledge of resources (38%) and in having the necessary training to intervene (19%). CONCLUSIONS: GPs see problem gambling as a legitimate role for their intervention, however, they have concerns around their competency and knowledge of resources. The provision of undergraduate and postgraduate training may assist to remove barriers to an accepted role in primary health.

Attitude of Health Personnel↗

Problem drinking profiles of patients presenting to general practitioners: analysis of Alcohol Use Disorders Identification Test (AUDIT) scores for the Auckland area.

AIM: To quantify the prevalence and demography of at-risk and problematic drinkers in the population attending a random selection of general practices and to compare this with similar studies. METHOD: A study examining the uptake and utilisation of the "DRINKLESS" package to 369 New Zealand general practitioners was conducted during 1995/6. The "DRINKLESS" package was developed with the World Health Organisation collaborative study for brief intervention for at-risk alcohol consumption. The package uses the Alcohol Use Disorders Identification Test (AUDIT). There were 15,670 completed AUDIT questionnaires collected during the study. These were analysed to ascertain the prevalence and demography of at-risk and problematic drinkers attending general practitioners. RESULTS: There were 16% of patients identified as having either "risky drinking" or "problematic or dependent drinking". This pattern varied according to the occupation, age and gender of patients. CONCLUSIONS: The data confirm that large numbers of patients presenting to general practitioners experience alcohol problems of varying degrees. This study also suggests that the AUDIT will have satisfactory detection rates in a primary care setting.

Adolescent↗

Brief screening for family psychiatric history: the family history screen.

BACKGROUND: Brief screens to collect lifetime family psychiatric history are useful in clinical practice and for identifying potential families for genetic studies. METHODS: The Family History Screen (FHS) collects information on 15 psychiatric disorders and suicidal behavior in informants and their first-degree relatives. Since each question is posed only once about all family members as a group, the administrative time is 5 to 20 minutes, depending on family size and illness. Data on the validity against best-estimate (BE) diagnosis based on independent and blind direct interviews on 289 probands and 305 relatives and test-retest reliability across 15 months in 417 subjects are presented. RESULTS: Agreement between FHS and BE diagnosis for proband and relative self-report had median sensitivity (SEN) of 67.6 and 71.1 respectively; median specificity (SPC) was 87.6 and 89.4, respectively. Marked decrease in SEN occurred when a single informant (the proband) reported on a relative (median, 37.5); however, median SPC was 95.8. Use of more than 1 informant substantially improved SEN (median, 68.2), with a modest reduction in SPC (median, 86.8). Test-retest reliability across 15 months resulted in a median kappa of 0.56. CONCLUSIONS: The FHS is a promising brief screen for collecting lifetime psychiatric history on an informant and/or first-degree relatives. Its validity is best demonstrated for major depression, anxiety disorders, substance dependence (alcohol and drug dependence), and suicide attempts. It is not a substitute for more lengthy family history if more detail on diagnosis is required.

Adolescent↗