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Biomedical subjects

M Newman

Publications and source records attributed to M Newman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of the interleukin-1 genotype on monocyte IL-1beta expression in subjects with adult periodontitis.

An association has been reported between polymorphisms in the genes encoding IL-1alpha (-889) and IL-1beta (+3953) (periodontitis susceptibility trait, PST), and an increased severity of periodontitis (18). The IL-1beta polymorphism was reported to correlate with increased IL-1beta expression by monocytes in response to bacterial stimulants. In the present study, we determined if PST positive subjects with periodontitis exhibit elevated production of IL-1beta, compared to PST negative periodontitis patients. Peripheral blood monocytes were obtained from 10 PST+ and 10 PST- age- and disease-balanced subjects with adult forms of periodontitis. Monocytes were cultured with a panel of bacterial stimulants, including Escherichia coli and Porphyromonas gingivalis LPS, and whole formalinized periodontal pathogens P. gingivalis, Bacteroides forsythus and Prevotella intermedia, and health-associated organisms Veillonella parvula and Streptococcus sanguis. Our results demonstrate that monocytes from PST+ and PST- patients showed no significant differences in IL-1beta production in response to any stimulant tested. In addition, the periodontal pathogens P. gingivalis, B. forsythus and P. intermedia failed to stimulate higher IL-1beta responses compared to health-associated species V. parvula and S. sanguis. A marked interindividual variation in production of IL-1beta was seen, with high, low and intermediate responders present in both PST+ and PST- groups. We conclude that genetic loci other than the PST polymorphisms are also important regulators of monocyte IL-1 responses.

Adult↗
PubMed2000

The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth. STUDY DESIGN: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at >/=37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score. RESULTS: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of >/=1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r =.51; P =.0001), sialidase activity (r =.38; P =.0001), and bacterial vaginosis (r =.38; P =.0001), were weakly related to fetal fibronectin (r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5. 5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4). CONCLUSIONS: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity.

Bacterial Infections↗
PubMed2000

Estimating the balance of general practice versus family planning clinic coverage of contraception services in London.

OBJECTIVE: To compare levels of provision of contraception from general practice and family planning clinics for the populations of the 32 London Boroughs. METHOD: Retrospective analysis of routine activity data, including the estimated numbers of first attendance, for 295 family planning clinics (managed by 28 NHS Trusts) and more than 1800 GP partnerships in Greater London, supplemented by data from a survey of family planning clinics. The results were expressed as the estimated percentage of women aged 16-49 obtaining advice on contraception from GPs and family planning clinics. These results were compared to those expected based on results in the General Household Survey. RESULTS: Across London in 1995/96, 12% of women aged 16-49 obtained contraception services from family planning clinics, and 24% obtained contraception services from a GP. At a borough level there was variation from 11% to 25% in coverage by family planning clinics, and from 11% to 41% in coverage by GPs. Estimates of the proportion of women in this age group not using NHS-provided medical or surgical contraception ranged from 0 to 30%. Across all boroughs, there was no consistent relationship between levels of GP activity and family planning clinic activity. CONCLUSION: The results indicate substantial variations between boroughs in the proportion of women using NHS-provided medical or surgical methods of contraception. The absence of any clear inverse relationship between activity in family planning clinics and activity in general practice suggests that changes to one will not be compensated by changes in the other. More specifically, health authorities that opt to purchase lower levels of family planning clinic activity cannot assume that women may opt to use GPs as an alternative. Such a strategy may increase the likelihood that women who would have used family planning clinic services will either not use contraception at all, or will use less effective 'over the counter' methods.

Adolescent↗
PubMed2000

Ileoanal pouch versus ileostomy: is there a difference in quality of life?

Ileoanal pouch (IAP) construction is arguably the procedure of choice to follow proctocolectomy for ulcerative colitis (UC) or familial adenomatous polyposis (FAP). Patients with UC or FAP at our institution choose their operation after counseling with the surgeon, with an enterostomal therapist, and with patients who have undergone IAP and proctocolectomy with ileostomy (IL). We studied these patients who chose IAP and IL, to determine differences in outcome and quality of life (QOL) between those two groups. We assessed outcomes by evaluating clinic and hospital records and surveyed patients' QOL via a standardized questionnaire. During a retrospective 10-year study period, 86 patients underwent evaluation for IAP construction for UC (64) and FAP (22). Fifty-five patients underwent IAP construction, and 31 underwent IL. There were no operative deaths. Thirty-four patients sustained 69 early and late complications (40%). The IAP group experienced a higher complication rate, 53 per cent, compared with the IL group, 16 per cent. Forty-five patients (56%) have completed questionnaires. Eighty-seven per cent of IAP patients and 93 per cent of IL patients responded that their overall QOL is "always" better since their operation (P = not significant). Both groups reported very favorable responses to questions regarding work, social life, family life, sleep, and relationships without statistically significant differences between the two groups. Despite a high complication rate, IAP is an excellent operation for many patients with UC or FAP, but patients who choose IL after preoperative counseling can be expected to have similar improvement in quality of life.

Adult↗
PubMed2000

HLA-binding peptides as a therapeutic approach for chronic HIV infection.

Herein, we describe the Epimmune approach to prophylaxis and development of a multi-epitope vaccine for immunotherapy of HIV-1 infection. The central strategy of our program is to induce cellular immune responses, cytotoxic T-lymphocytes (CTL) and helper Tlymphocytes (HTL), specific for conserved epitopes from both structural and regulatory proteins of HIV-1. The HIV-1 derived and HLA-restricted CTL and HTL epitopes needed to design and construct the experimental vaccines are now known and allow for broad and non-ethnically biased coverage of the human population. The design optimization of an epitope-based DNA vaccine and evaluating methods for various DNA vaccine delivery technologies for possible use in clinical trials are addressed.

Journal Article↗
PubMed1999

Moyamoya disease in a 12-year-old Caucasian boy presenting with acute transient psychosis.

This paper reports the case of a 12-year-old boy who presented with an acute transient psychosis. Investigations revealed Moyamoya disease with occlusion of the left middle cerebral artery. There was no previous history of transient ischaemic attacks, no history of psychiatric disease, no family history of psychosis and no history of illicit drug use. Although no previous cases of Moyamoya disease with psychosis as the sole presenting feature have been described, we suggest the possibility of a causal link.

Acute Disease↗
PubMed1999

Differential expression of neutrophil adhesion molecules during coronary artery surgery with cardiopulmonary bypass.

BACKGROUND: Activation of neutrophil adhesion molecules and subsequent neutrophil adhesion to vascular endothelium are key events initiating inflammatory organ dysfunction after cardiopulmonary bypass and ischemic reperfusion. OBJECTIVES: We sought to characterize neutrophil integrin CD11b and L-selectin activation associated with coronary artery bypass graft surgery and to determine whether neutrophil activation contributes to their sequestration on postbypass reperfusion. METHODS: Twenty patients undergoing routine coronary artery bypass were studied. Heparinized whole blood was simultaneously sampled from a central venous line, aorta, coronary sinus, and right and left atrium before, during, and up to 20 minutes after cardiopulmonary bypass. Neutrophil counts were obtained, and neutrophil CD11b and L-selectin expression was determined by flow cytometric analysis in whole blood. RESULTS: CD11b expression on circulating neutrophils increased during cardiopulmonary bypass, peaking at 145% of baseline level after release of the aortic clamp and then declined by 20 minutes after bypass (analysis of variance, P =.003). No change in neutrophil L-selectin expression was observed during cardiopulmonary bypass. Neutrophils responded to ex vivo stimulation by C5a and leukotriene B(4) during cardiopulmonary bypass but not at 24 hours after the operation. After reperfusion, neutrophil loss, but not local activation, was demonstrated in the coronary and pulmonary circulations. CONCLUSIONS: Upregulated CD11b expression on neutrophils is likely to contribute to neutrophil sequestration in the heart and lungs after bypass, but neutrophil activation may be limited by their reduced responsiveness to agonist stimulation. CD11b represents a potential therapeutic target for diminishing inflammation after cardiac operations.

CD11 Antigens↗
PubMed1999

Perception of cognitive function in older adults following coronary artery bypass surgery.

This study examined the effects of coronary artery bypass grafting (CABG) on objective and subjective measures of neurocognitive functioning. Participants were 170 older patients (127 men and 43 women; mean age = 61 years) undergoing CABG. Measures of neurocognitive function, depression, anxiety, and perceived cognitive abilities were administered immediately prior to and 6 weeks following surgery. Although objective measures of impaired cognitive performance following CABG were not related to perceived cognitive difficulties, the presence of anxiety and depression was related to the perception of cognitive functioning. Patients who reported high levels of anxiety and depression 6 weeks after surgery perceived themselves as having poorer cognitive function. Interventions designed to reduce emotional distress could improve patient's perceived cognitive abilities following CABG.

Aged↗
PubMed1999

Growth hormone-mediated regulation of insulin-like growth factor I promoter activity in C6 glioma cells.

The molecular mechanisms by which GH regulates insulin-like growth factor (IGF-I) gene expression remain obscure. One difficulty has been the lack of established GH-responsive cell lines that express the IGF-I gene. To develop such a cell line, we used rat C6 glioma cells which, as determined by RNase protection assay, express the IGF-I gene but not the GH receptor gene. To confer GH responsiveness, C6 cells were cotransfected with vectors that express the GH receptor (pRc/CMV WTrGHR) and Jak2 (pRc/CMV Jak2). GH responsiveness was demonstrated using luciferase reporter genes containing either the Sis-inducible element from the c-fos gene (pTK81-SIE-Luc) or 6 copies of the GH-responsive GAS-like element (GLE) from the rat spi2.1 gene (pSpi-GLE-Luc). The SIE is activated by binding of STAT1 and 3, whereas the GLE binds STAT5. In cells cotransfected with pRc/CMV WTrGHR, pRc/CMV Jak2, and either pTK81-SIE-Luc or pSpi GLE-Luc, treatment with 500 ng/ml GH for 24 h stimulated a 3.1- and 1.7-fold increase in luciferase activity, respectively. These data suggest that in C6 cells cotransfected with pRc/CMV WTrGHR and pRc/CMV Jak2, GH activates STAT1, 3, and 5. To determine whether GH-responsive IGF-I promoter activity could be demonstrated, C6 cells were cotransfected with pRc/CMV WTrGHR, pRc/ CMV Jak2, and an IGF-I-luciferase fusion gene that contained a fragment of the rat IGF-I gene that extended from -412 in the 5'-flanking region of exon 1 to the Met-22 in exon 3. GH stimulated a modest, but reproducible, 1.7-fold increase in luciferase activity in these cells, suggesting that a GH-responsive element is present in this region of the IGF-I gene. To better localize the GH-responsive element, cells were cotransfected with pRc/CMV WTrGHR, pRc/CMV Jak2 plus one of several IGF-I-luciferase fusion genes containing either fragments of one of the two promoters in the IGF-I gene or a fragment of intron 2 that includes a GH-responsive DNase I hypersensitivity site. For all constructs, treatment with GH for 24 h did not stimulate a significant increase in luciferase activity, suggesting that GH-responsive sequences are not located in these specific regions of the IGF-I gene or that GH-directed transcription of the IGF-I gene is mediated via several different regions of the IGF-I gene and the effect of any one of these regions in isolation was not sufficiently robust to be detected in this model system. In summary, transient expression of the GH receptor and Jak2 in C6 cells creates a GH-responsive system that activates STAT1, 3, and 5. Moreover, a fragment of the IGF-I gene that contains exons 1 and 2, a fragment of exon 3, and introns 1 and 2 is GH responsive using this model system.

Animals↗
PubMed1999

Ileoanal pouch procedures: clinical outcomes and quality-of-life assessment.

Ileoanal pouch (IAP) anastomosis following total colectomy for ulcerative colitis or familial adenomatous polyposis is performed with the goal of avoiding a permanent ileostomy and its effects on life satisfaction. During a retrospective 10-year study period, 55 patients underwent IAP construction for ulcerative colitis (36) and familial adenomatous polyposis (19). We assessed complications by chart review and surveyed patients regarding quality of life via a standardized questionnaire. There was no operative mortality, and there were three late deaths (6%). Twenty-nine patients (54%) sustained 68 early and late complications. Pouchitis was the most common complication (24%), and two patients required pouch excision (4%), one for pouchitis and one for rectovaginal fistula. Thirty-one patients (65%) have completed questionnaires. Forty-seven patients (87%) responded that their overall quality of life is "always" better since creation of the IAP, and only one patient in the IAP group has greater than ten bowel movements a day. Twenty-one patients (68%) never have interference with intimate relationships and 20 (65%) never have interference with physical activities. However, 20 patients (65%) sometimes have sleep interference, and 19 patients (61%) sometimes have fecal soilage. None of the patients continue to take steroids. We conclude that the complication rate following IAP construction is high, but pouch loss is infrequent. Despite a high complication rate, the majority of patients experience an improvement in quality of life.

Adenomatous Polyposis Coli↗
PubMed1998

Crystal structure of restriction endonuclease BglI bound to its interrupted DNA recognition sequence.

The crystal structure of the type II restriction endonuclease BglI bound to DNA containing its specific recognition sequence has been determined at 2.2 A resolution. This is the first structure of a restriction endonuclease that recognizes and cleaves an interrupted DNA sequence, producing 3' overhanging ends. BglI is a homodimer that binds its specific DNA sequence with the minor groove facing the protein. Parts of the enzyme reach into both the major and minor grooves to contact the edges of the bases within the recognition half-sites. The arrangement of active site residues is strikingly similar to other restriction endonucleases, but the co-ordination of two calcium ions at the active site gives new insight into the catalytic mechanism. Surprisingly, the core of a BglI subunit displays a striking similarity to subunits of EcoRV and PvuII, but the dimer structure is dramatically different. The BglI-DNA complex demonstrates, for the first time, that a conserved subunit fold can dimerize in more than one way, resulting in different DNA cleavage patterns.

Bacillus↗
PubMed1998

Prenatal sonographic appearance of congenital fibrosarcoma.

Congenital fibrosarcoma is a rare soft tissue sarcoma. A 22-year-old woman in the 22nd week of her first pregnancy underwent sonographic examination, which revealed a soft tissue swelling of the fetus's left thigh. The pregnancy was terminated, and congenital fibrosarcoma was diagnosed by pathologic examination. To our knowledge, this is the first published report of the intrauterine sonographic observation of this tumor in a fetal extremity.

Adult↗
PubMed1998

Epstein-Barr virus-infected marmoset cells transfected with c-myc do not form lymphomas in mice with severe combined immunodeficiency.

Epstein-Barr virus (EBV) has been associated with several malignant processes in man, most notably Burkitt lymphoma in previously healthy individuals and lesions resembling large cell non-Hodgkin lymphomas in organ transplant recipients. Mice with the severe combined immunodeficiency phenotype (SCID mice) are exquisitely susceptible to the development of EBV-associated lymphoproliferative lesions following the intraperitoneal (ip) inoculation of EBV-infected human lymphocytes. Recently, we reported that EBV-infected marmoset lymphocytes do not form lymphomas in SCID mice following ip injection, while human lymphocytes infected with the same EBV strains do. On the assumption that the EBV-infected marmoset cells were lacking a factor necessary for tumor formation, we transfected a plasmid containing c-myc into EBV-infected marmoset cells (B95-8, FF41, and W91 cells). Despite expression of the c-myc protein as determined by immunoblot and flow cytometry when probed with a monoclonal antibody, no increase over baseline lesion development was seen in SCID mice inoculated with 5 x 10(6) c-myc-expressing marmoset lymphoblastoid cells. Thus, cells that express c-myc and harbor EBV are not sufficient to form lymphomas in certain immunocompromised hosts.

Animals↗
PubMed1998

Barriers to evidence-based practice.

OBJECTIVES: This paper reports the findings of a study which aimed to identify the barriers to evidence-based practice in an acute National Health Service (NHS) trust. The study was carried out as part of an action research project designed to promote evidence-based practice. DESIGN: A rapid organizational appraisal design was used. This involved formal and informal interviews, focus groups, and observation of staff interactions at meetings and in clinical practice in an acute hospital NHS trust. Interviews were undertaken with key stakeholders within the organization and focus groups held with nurse managers, audit staff, staff nurses, and junior medical staff. Observation took place in meetings and in clinical areas. RESULTS: At an organizational level, the main issues identified were: (1) evidence-based practice was a low management priority, (2) problems with dissemination, (3) inadequate systems for personal and professional development, (4) difficulties in the management of innovations, (5) accessing evidence and resource constraints. At the individual practice level, the main issues were motivation, a lack of clarity about roles and practice, and a culture of practice which emphasizes 'routine' patient care. CONCLUSIONS: The results of this study demonstrate that structures and cultures within organizations can be important barriers to evidence-based practice. Factors which are external to individual trusts are also important. Existing hierarchical structures both in the NHS and within and between the different professional groups, are manifest in the existence of a largely deferential culture which emphasizes the routine in practice decision making. Given this reality, organizations will have to adopt multiple strategies to facilitate and promote the use of evidence in practice decision making.

Attitude of Health Personnel↗
PubMed1998

Health authority commissioning for quality in contraception services.

OBJECTIVE: To compare the commissioning of contraception services by London health authorities with accepted models of good practice. DESIGN: Combined interview and postal surveys of all health authorities and National Health Service (NHS) trusts responsible for running family planning clinics in the Greater London area. MAIN OUTCOME MEASURES: Health authority commissioning was assessed on the presence of four key elements of good practice--strategies, coordination, service specifications, and quality standards in contracts--by monitoring activity and quality. RESULTS: Less than half the health authorities surveyed had written strategies or service specifications for contraception services. Arrangements for coordination of services were limited and monitoring was underdeveloped. CONCLUSION: The process of commissioning services for contraception seems to be relatively underdeveloped despite the importance of health problems associated with unplanned pregnancy in London. These findings raise questions about the capacity of health authorities to improve the quality of these services through the commissioning process.

Adult↗