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Biomedical subjects

J Spencer

Publications and source records attributed to J Spencer.

At least 109 records · Page 6Linked to original sources

The Department of Veterans Affairs' NSQIP: the first national, validated, outcome-based, risk-adjusted, and peer-controlled program for the measurement and enhancement of the quality of surgical care. National VA Surgical Quality Improvement Program.

OBJECTIVE: To provide reliable risk-adjusted morbidity and mortality rates after major surgery to the 123 Veterans Affairs Medical Centers (VAMCs) performing major surgery, and to use risk-adjusted outcomes in the monitoring and improvement of the quality of surgical care to all veterans. SUMMARY BACKGROUND DATA: Outcome-based comparative measures of the quality of surgical care among surgical services and surgical subspecialties have been elusive. METHODS: This study included prospective assessment of presurgical risk factors, process of care during surgery, and outcomes 30 days after surgery on veterans undergoing major surgery in 123 medical centers; development of multivariable risk-adjustment models; identification of high and low outlier facilities by observed-to-expected outcome ratios; and generation of annual reports of comparative outcomes to all surgical services in the Veterans Health Administration (VHA). RESULTS: The National VA Surgical Quality Improvement Program (NSQIP) data base includes 417,944 major surgical procedures performed between October 1, 1991, and September 30, 1997. In FY97, 11 VAMCs were low outliers for risk-adjusted observed-to-expected mortality ratios; 13 VAMCs were high outliers for risk-adjusted observed-to-expected mortality ratios. Identification of high and low outliers by unadjusted mortality rates would have ascribed an outlier status incorrectly to 25 of 39 hospitals, an error rate of 64%. Since 1994, the 30-day mortality and morbidity rates for major surgery have fallen 9% and 30%, respectively. CONCLUSIONS: Reliable, valid information on patient presurgical risk factors, process of care during surgery, and 30-day morbidity and mortality rates is available for all major surgical procedures in the 123 VAMCs performing surgery in the VHA. With this information, the VHA has established the first prospective outcome-based program for comparative assessment and enhancement of the quality of surgical care among multiple institutions for several surgical subspecialties. Key features to the success of the NSQIP are the support of the surgeons who practice in the VHA, consistent clinical definitions and data collection by dedicated nurses, a uniform nationwide informatics system, and the support of VHA administration and managerial staff.

Hospitals, Veterans↗

Overexpression, purification, and characterization of the cloned metallo-beta-lactamase L1 from Stenotrophomonas maltophilia.

The metallo-beta-lactamase L1 from Stenotrophomonas maltophilia was cloned, overexpressed, and characterized by spectrometric and biochemical techniques. Results of metal analyses were consistent with the cloned enzyme having 2 mol of tightly bound Zn(II) per monomer. Gel filtration chromatography demonstrated that the cloned enzyme exists as a tightly held tetramer with a molecular mass of ca. 115 kDa, and matrix-assisted laser desorption ionization and time-of-flight mass spectrometry indicated a monomeric molecular mass of 28.8 kDa. Steady-state kinetic studies with a number of diverse penicillin and cephalosporin antibiotics demonstrated that L1 effectively hydrolyzes all tested compounds, with k(cat)/Km values ranging between 0.002 and 5.5 microM(-1) s(-1). These characteristics of the recombinant enzyme are contrasted to those previously reported for metallo-beta-lactamases isolated directly from S. maltophilia.

Chromatography, Gel↗

Meckel's diverticulum: angiographic findings in 16 patients.

OBJECTIVE: The purpose of this study was to assess the sensitivity of angiography in revealing the vitellointestinal artery or other arteriographic abnormalities in patients in whom surgery subsequently proved Meckel's diverticulum. MATERIALS AND METHODS: From the 36 patients who had undergone a Meckel's diverticulectomy between 1980 and 1997 at Hammersmith Hospital or a referring hospital, we selected 18 who had undergone preoperative angiography at our institution. Case notes and angiograms of these 18 patients were reviewed for the presence of a persistent vitellointestinal artery or other angiographic evidence of a Meckel's diverticulum. RESULTS: Angiograms of 16 of 18 patients were available for review. A striking male preponderance existed (male:female = 13:3). Mean age was 28 years (range, 12-65 years). In 11 (69%) of the 16 patients, a persistent vitellointestinal artery was seen that had been noted at the time of the study and reported before surgery for nine patients. Other angiographic abnormalities at the site of the Meckel's diverticulum were present in four patients and included a vascular blush, early venous return, and arterial irregularity. CONCLUSION: Angiography will show a persistent vitellointestinal artery in most individuals with a Meckel's diverticulum who present with chronic gastrointestinal bleeding. However, the recognition of a persistent vitellointestinal artery may be difficult because of overlying vessels, and superselective catheterization of distal ileal arteries may be necessary.

Adolescent↗

Evaluation of death registers in general practice.

BACKGROUND: General practitioners (GPs) do not routinely receive information about the deaths of those patients whose death certificates they have not completed. We developed and evaluated a system for producing death registers for GPs. AIM: To evaluate GPs' and practice managers' views on, and uses of, the death register. METHOD: General practitioners in Newcastle (n = 161) and Sunderland Family Health Service Authority (n = 144) areas were sent a questionnaire on their sources and use of information about patients' deaths. Death registers were sent to Newcastle practices; Sunderland practices were the control group. A follow-up questionnaire was sent to Newcastle (n = 173) and Sunderland (n = 140) GPs after two years. Newcastle practice managers (n = 45) were interviewed after their practice had received death registers for one year. RESULTS: Ninety-two per cent of Newcastle responders had seen the death register. Seventy-three per cent saw it regularly. Of those who saw it, 92% found it useful for communication within the primary health care team, bereavement follow-up, and administration and medical audit. One fifth of GPs named the death register as their first source of information about their patients' deaths. Newcastle GPs reported greater levels of change in use of patient death information than the control group. Practice managers circulated, used, and recorded information from the death register. CONCLUSION: Death registers are valued and have demonstrable benefits with regard to administration, bereavement care, and medical audit.

Attitude of Health Personnel↗

Genomic imprinting in the rat: linkage of Igf2 and H19 genes and opposite parental allele-specific expression during embryogenesis.

Igf2 and H19 are closely linked imprinted genes in both mice and humans that are expressed from opposite parental alleles. In this study we demonstrate that these two genes are also closely linked in the rat, with the H19 gene mapping to within 145 kb of Igf2 on rat chromosome 1. We identified polymorphisms in H19 and Igf2 transcripts in two inbred rat strains and determined the expression of the parental alleles in F1 offspring. The H19 gene was shown to be expressed exclusively from the maternal allele in all fetal and neonatal tissues. Monoallelic expression of Igf2 from the paternal allele was found in all tissues except the leptomeninges and choroid plexus. Igf2 in the choroid plexus was monoallelic at days 13.5 and 15.5 of gestation with a switch to biallelic expression by day 18.5, demonstrating a loss of imprinting after the choroid plexus has differentiated. Biallelic expression of Igf2 was observed in the leptomeninges at all fetal and neonatal stages analyzed. These studies demonstrate conservation of imprinting of two closely linked genes transcribed from opposite parental alleles in a species other than human or mouse. A comparative approach between different species will be important in defining the mechanisms that regulate the tissue-specific expression of imprinted genes.

Alleles↗

Magnesium ions are required for HEp-2 cell adhesion by enteroaggregative strains of Escherichia coli O126:H27 and O44:H18.

Enteroaggregative strains of Escherichia coli, belonging to serotypes O44:H18 and O126:H27, were used to show that magnesium ions were essential for the adhesion of these enteroaggregative strains to HEp-2 cells. The removal of Mg2+ ions from culture media was correlated with the inability of strains to produce an outer membrane-associated protein of 18 kDa and a pellicle. It was concluded that magnesium ions were directly involved with the expression of an 18 kDa outer membrane-associated protein by strains of E. coli O126:H27 and O44:H18, and that the outer membrane-associated protein was involved in both HEp-2 adhesion and pellicle formation.

Antibody Specificity↗

Is the structure of the N-domain of phosphoglycerate kinase affected by isolation from the intact molecule?

The structural integrity of the isolated N-domain (residues 1-174) of Bacillus stearothermophilus 3-phosphoglycerate kinase (PGK) has been investigated using heteronuclear NMR spectroscopy. Analysis of 13C chemical shifts, amide protection, and comparison of observed and expected sequential NOE intensities calculated from the crystal structure of the domain in the intact protein indicate that the secondary structure of the isolated domain is unchanged from that found in the intact molecule. Markedly shifted 1H resonances, amide protection, and long-range NOEs indicate that the tertiary structure is similarly unaffected. These results are confirmed by an excellent agreement (standard deviation 0.28 ppm) between observed H alpha chemical shifts and those calculated from the high-resolution (1.6 A) crystal structure of intact PGK [Davies et al. (1994) Acta Crystallogr. D50, 202-209]. The only region perturbed by loss of interactions with the C-domain is a small portion of the substrate-binding site (residues 148-152) whose amide protons are poorly protected from solvent. These results provide a structural basis for the analysis of the folding of the domains of PGK as isolated units and within the intact molecule [Parker et al. (1996) Biochemistry (in press)] and contrast with the notion that the native tertiary fold of the N-domain of PGK requires the whole polypeptide chain, including the entire C-domain [Mas et al. (1995) Biochemistry 34, 7931-7940]. Assignments of backbone 13C, 15N, HN, and H alpha resonances are provided.

Amino Acid Sequence↗

Sequence analysis of human IgVH genes indicates that ileal lamina propria plasma cells are derived from Peyer's patches.

The origin of human ileal lamina propria (LP) plasma cells has been investigated using a technique based on microdissection of cells from immunohistochemically stained tissue sections. We have sequenced rearranged IgVH4.2 1, IgVH 5 family and IgVH6 genes from Peyer's patch germinal center (GC) cells and plasma cells from the ileal LP. Clonally related cells were identified by comparison of their complementarity determining region (CDR) 3 sequences and patterns of somatic mutation. We observed Ig genes from B cells in the GC of Peyer's patches which were related to Ig genes from plasma cells in the ileal LP, demonstrating that clonally related cells span these sites. In addition, groups of clonally related. but diversified plasma cells were common in the lamina propria. All Ig genes isolated from LP plasma cells were heavily mutated. The distribution of mutations in the CDR of the Ig heavy chain variable region (VH) genes which were considered to be the expressed alleles in LP plasma cells was consistent with an affinity-matured response. These observations provide compelling evidence for the origin of human ileal plasma cells from the Peyer's patches.

Amino Acid Sequence↗

Hypermutation, diversity and dissemination of human intestinal lamina propria plasma cells.

In this work we have microdissected lamina propria plasma cells and used polymerase chain reaction and sequencing to investigate immunoglobulin (Ig) gene rearrangements and mutations in human intestine. In addition, specific primers were designed for individual Ig gene rearrangements to analyze the distribution of related B cell and plasma cell clones at different sites along the bowel. Confirming our earlier work, intestinal IgVH genes were highly mutated in plasma cells from older individuals (> 30 years). IgVH genes were significantly less mutated in samples taken from patients aged 11-30 years, and there were fewer mutations again in samples from young children (< 11 years). In age-matched specimens the number of mutations was equivalent in the duodenum and colon. Using complementarity-determining region 3 primers to amplify specific Ig gene rearrangements, evidence was also found for the existence of related lamina propria plasma cells along the small bowel and colon, although these were quite scarce. In addition, analysis of the numbers of related clones in a random sampling from discrete areas of lamina propria indicates that the local population is diverse. These results suggest that the highly mutated IgVH genes in adult intestinal plasma cells are a consequence of chronic antigen exposure with age. Duodenal plasma cells are as highly mutated as colonic plasma cells, despite the fact that the upper bowel has no indigenous microbial flora (the stimulus for intestinal plasma cells). They also show that the plasma cell population is diverse and can be widely disseminated along the bowel.

Adolescent↗

CD95 and CD95-ligand expression in endocrine pancreas of NOD, NOR and BALB/c mice.

The non-obese diabetic (NOD) mouse is widely used to study the pathogenesis of insulin-dependent diabetes mellitus. However, the mechanisms responsible for beta-cell destruction, in this model, are still poorly defined. The CD95/CD95L system among other effector systems has been implicated in beta-cell death. In this study we investigated in NOD, non-obese resistant (NOR) and Balb/c mice the expression of CD95 and CD95L in alpha and beta pancreatic cells by immunohistochemistry and immunofluorescence. We demonstrate that alpha cells in the islets of Langherans constitutively express CD95L forming a natural shield around beta cells.

Animals↗

Estimation of exposure from spilled glutaraldehyde solutions in a hospital setting.

Glutaraldehyde is commonly used in hospitals for cold disinfection of instruments which may be damaged by autoclaving. The increased use of automatic washer/disinfection machines has resulted in a greater risk of spills than with manual methods. A series of experiments was conducted to answer two related research questions: what was the likely range of airborne concentrations when glutaraldehyde is spilled, and are commonly used personal protective equipment ensembles effective and practicable in use? Objective measurements using three sampling methods (two pumped methods based on OSHA 64, one using treated filters and the other based on adsorbent tubes, and a Glutaraldemeter direct reading instrument) were conducted with spills of various surface areas of both 2 and 50% solutions of glutaraldehyde. Results ranged between < 0.01 and 1.4 ppm. Two personal protective equipment ensembles were tested. One was based on a half-facepiece respirator with gas-tight goggles, while the other comprised a full-facepiece cartridge respirator. Both ensembles gave adequate protection against irritation, although in use the half-facepiece respirator and goggles tended to interfere with each other. The direct reading instrument generally underestimated the glutaraldehyde concentrations, although there was a significant association with the results obtained using the method based on adsorbent tubes.

Accidents, Occupational↗