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Biomedical subjects

C S Baker

Publications and source records attributed to C S Baker.

At least 37 records · Page 2Linked to original sources

Achievable benchmarks of care: the ABCs of benchmarking.

Benchmarking is generally considered to be an important tool for quality improvement. Traditional approaches to benchmarking have relied on subjective identification of 'leaders in the field'. We derive an objective, reproducible and attainable Achievable Benchmark of Care (ABC) by measuring and analysing performance on process-of-care indicators. Three characteristics of the ABC that we deem essential are: (1) benchmarks represent a measurable level of excellence; (2) benchmarks are demonstrably attainable; (3) benchmarks are derived from data in an objective, reproducible and predetermined fashion. From these characteristics it follows that (4) providers with high performance are selected to define a level of excellence in a predetermined fashion, but (5) providers with high performance on small numbers of cases do not influence unduly benchmark levels. We use the 'pared mean' to operationalize the ABC. Roughly, the pared mean summarizes the performance of top-ranked providers whereby at least 10% of the patient pool across all providers is included. Bayesian estimators for adjustment of performance of providers with small sample sizes are used to rank providers. Randomized controlled trials to assess the independent effect of the ABC in quality improvement projects are under way. We have developed a methodology objectively and reproducibly to derive a level of excellent, attainable performance, based on measured performance by a group of providers. The ABC can be applied to groups of providers in communities, to institutions and departments within them, or to individual practitioners.

Bayes Theorem↗

Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages.

Inflammation appears to have a major role in the development of atherosclerotic lesions affecting native and transplanted coronary arteries. The subsequent risk of plaque rupture and acute ischemic events correlates with the degree of inflammation and may be modified by aspirin, an anti-inflammatory cyclooxygenase inhibitor. Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) are involved in the inflammatory response via the rapid and exaggerated production of prostanoids and nitric oxide, both of which may have proatherosclerotic effects. These effects may be mediated by the formation of peroxynitrite in the case of nitric oxide and involve "cross talk" between the two enzyme systems. This study aimed to investigate native and transplant atherosclerosis for the presence and distribution of Cox-2 and iNOS. Immunocytochemical studies were performed on atherosclerotic lesions from patients with native (n=12) and transplant (n=5) coronary disease by using antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of peroxynitrite production). Control tissue was obtained from unused donor hearts and at the time of autopsy. Cox-2 and iNOS colocalized predominantly in macrophages/foam cells in both types of atherosclerosis. Cox-2 expression was also detected in medial smooth muscle cells and endothelial cells, including those of the vasa vasorum. Nitrotyrosine was found in the same distribution as that of iNOS and was colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native and transplant atherosclerosis, possibly allowing for interaction between the enzymes and suggesting an alternative mechanism for the benefits of aspirin via inhibition of Cox-2 activity.

Animals↗

Impact of atrial fibrillation on mortality, stroke, and medical costs.

BACKGROUND: The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown. METHODS: We conducted a prospective cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis (CVD) compared with a matched group without AF (n = 26,753), randomly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF. Stroke rates were also determined in another cohort free of CVD (n = 14,267). Total medical costs after hospitalization were available from a 1991 cohort. Cumulative mortality, stroke rates, and costs following index admission were adjusted by multivariate and proportional hazard regression analyses. RESULTS: Mortality rates were high in individuals with CVD, ranging from 19.0% to 52.1% in 1 year. Adjusted relative mortality risk was approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P < .05). Incidence of stroke was high in individuals with CVD, 6.2% to 15.4% in 1 year, with and without AF, and was at least 5-fold higher than in individuals without CVD. In those with CVD, stroke rates were approximately 25% higher in women with AF (P < .05) but only 10% higher in men. Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men, and 9.8- to 11.2-fold greater in women with AF (P < .05). Second- and third-year costs were increased as well. CONCLUSION: Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs.

Age Distribution↗

Molecular genetic identification of southern hemisphere beaked whales (Cetacea: Ziphiidae).

To assist in the species-level identification of stranded and hunted beaked whales, we compiled a database of 'reference' sequences from the mitochondrial DNA control region for 15 of the 20 described ziphiid species. Reference samples for eight species were obtained from stranded animals in New Zealand and South Australia. Sequences for a further seven species were obtained from a previously published report. This database was used to identify 20 'test' samples obtained from incompletely documented strandings around New Zealand. Analyses showed that four of these 'test' specimens (20%) had initially been misidentified. These included two animals of particular interest: (i) a Blainville's beaked whale (Mesoplodon densirostris), the first record of this species in New Zealand waters; and, (ii) a juvenile Andrews' beaked whale (Mesoplodon bowdoini), a species known from just over 20 strandings worldwide. A published sequence from a beaked whale product purchased in the Republic of Korea was identified as a Cuvier's beaked whale (Ziphius cavirostris). Levels of intra- and interspecific variation were compared to determine the potential for misidentification when the database or taxonomy is incomplete. Intraspecific variation was generally < 2%, and interspecific divergence was generally > 4.7%. Exceptions were within-species variation in Hyperoodon planifrons, southern bottlenosed whale (4.12%), which exceeded the variation between the two species of Berardius (3.78%), and variation between the two specimens assigned to M. hectori, Hector's beaked whale (7.14%). The latter case appears to be an error in species identification, and could represent the discovery of a new species of beaked whale.

Animals↗

Population structure of nuclear and mitochondrial DNA variation among humpback whales in the North Pacific.

The population structure of variation in a nuclear actin intron and the control region of mitochondrial DNA is described for humpback whales from eight regions in the North Pacific Ocean: central California, Baja Peninsula, nearshore Mexico (Bahia Banderas), offshore Mexico (Socorro Island), southeastern Alaska, central Alaska (Prince Williams Sound), Hawaii and Japan (Ogasawara Islands). Primary mtDNA haplotypes and intron alleles were identified using selected restriction fragment length polymorphisms of target sequences amplified by the polymerase chain reaction (PCR-RFLP). There was little evidence of heterogeneity in the frequencies of mtDNA haplotypes or actin intron alleles due to the year or sex composition of the sample. However, frequencies of four mtDNA haplotypes showed marked regional differences in their distributions (phi ST = 0.277; P < 0.001; n = 205 individuals) while the two alleles showed significant, but less marked, regional differences (phi ST = 0.033; P < 0.013; n = 400 chromosomes). An hierarchical analysis of variance in frequencies of haplotypes and alleles supported the grouping of six regions into a central and eastern stock with further partitioning of variance among regions within stocks for haplotypes but not for alleles. Based on available genetic and demographic evidence, the southeastern Alaska and central California feeding grounds were selected for additional analyses of nuclear differentiation using allelic variation at four microsatellite loci. All four loci showed significant differences in allele frequencies (overall FST = 0.043; P < 0.001; average n = 139 chromosomes per locus), indicating at least partial reproductive isolation between the two regions as well as the segregation of mtDNA lineages. Although the two feeding grounds were not panmictic for nuclear or mitochondrial loci, estimates of long-term migration rates suggested that male-mediated gene flow was several-fold greater than female gene flow. These results include and extend the range and sample size of previously published work, providing additional evidence for the significance of genetic management units within oceanic populations of humpback whales.

Alleles↗

Spontaneously terminating ventricular fibrillation and asystole induced by silent ischaemia causing recurrent syncope.

A 57 year old man was admitted for investigation of recurrent syncopal attacks. Holter monitoring during an attack while in hospital revealed a unique sequence of gross ST segment elevation, ventricular tachycardia, prolonged ventricular fibrillation, asystole, junctional and ventricular escape rhythm, and finally spontaneous restoration of sinus rhythm with severe ST segment depression. Subsequent coronary arteriography demonstrated severe stenoses of the right coronary artery, prompting percutaneous transluminal angioplasty and stenting. The patient has had no further syncopal attacks.

Angioplasty, Balloon, Coronary↗

Pulmonary surfactant composition early in development of acute lung injury after cardiopulmonary bypass: prophylactic use of surfactant therapy.

Cardiopulmonary bypass surgery (CPB) causes lung injury and at least 2% of adult patients and more children develop the most severe from acute respiratory distress syndrome (ARDS). Pulmonary surfactant deficiency contributes to the pathogenesis of ARDS. It has been proposed that surfactant therapy immediately after CPB might arrest progression to ARDS. However, many patients develop only mild lung injury after CPB. Thus early markers are needed to identify those patients at highest risk to guide selection for treatment. The aim of this study was to determine whether changes in surfactant phospholipids occur, and reflect severity of lung injury within the first few hours after bypass. Because of the relatively low incidence of ARDS in adult patients, this study was conducted using young pigs highly susceptible to bypass-induced lung injury. Eight pigs were given 2 hours bypass. Six controls underwent 'sham' bypass. At 3 h after bypass pulmonary vascular endothelial permeability was assessed by transcapillary leakage of radiolabelled transferrin. A 4 hour broncho-alveolar lavage (BAL) was used to assess intra-alveolar levels of surfactant, inflammatory cells and oedema protein. Bypass caused falls in arterial oxygenation and lung compliance (P < 0.01), but at this early stage in progression of lung injury BAL surfactant phospholipid and albumin levels were within the control range indicating that the alveolar epithelium had not yet suffered major damage. The main abnormalities were increases in vascular endothelial permeability (P < 0.01), BAL neutrophils (P < 0.01), total protein and sphingomyelin (SM) (P < 0.05). Lung histology showed that the main damage was interstitial oedema located around the bronchioles and their associated vessels. A single instilled dose of surfactant phospholipids in 5 animals caused excess in vivo supplementation and did not reduce the early pathophysiologic changes. Our findings suggest that surfactant phospholipid deficiency does not make a major contribution in the initial stages of lung injury after CPB, and that excessive phospholipid supplementation at this stage can be deleterious.

Animals↗

Medicare treatment differences for blacks and whites.

OBJECTIVES: This study investigated racial differences in procedure use among elderly Medicare beneficiaries. It is hypothesized that providers do not discriminate inappropriately in treating black and white patients and that the apparent differences in black-white treatment could be attributed to other differences between the two populations. METHODS: Rates of use for selected procedures were examined among two patient groups: (1) the universe of Medicare beneficiaries in 10 states and the District of Columbia and (2) a subset of this sample created by matching beneficiaries on the basis of zip code of residence to neutralize the effects of black-white differences in provider access and regional practice patterns. Because all Medicare beneficiaries have a common core of standard benefits, the importance of financial access differences in accounting for black/white utilization differences is diminished. RESULTS: Three major findings were indicated from this study: (1) area-controlled comparisons find even larger black-white disparities than those shown from uncontrolled comparisons, (2) the disparities are larger in southern states, and (3) the disparities vary substantially with procedure cost. CONCLUSIONS: Although no clinical data were analyzed, providers appeared to be giving less intensive treatment to otherwise similar black Medicare beneficiaries.

Black or African American↗

Photosensitivity.

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Acquired Immunodeficiency Syndrome↗

HLA-DR4 may determine expression of actinic prurigo in British patients.

Human leukocyte antigen (HLA) associations have been reported in Amerindian patients with actinic prurigo. To determine if similar associations are present in the British Caucasoid population with actinic prurigo, 26 patients underwent serological typing for HLC Class I and II antigens. DNA analysis by both sequence-specific priming and group-specific amplification with single-stranded oligonucleotide probe hybridization was used to confirm the DR and DQ typing and to perform DR4 subtyping. All patients were DR4 positive, and 25 of 26 patients were DQ7 positive. DR4 subtyping revealed 12 of 20 patients tested to be DRB1*0407. A nonsignificant association was also found with HLA B55 that is in linkage disequilibrium with DRB1*0407. No HLA associations were found in 25 British Caucasoid patients with polymorphic light eruption. DRB1*0407 is rare in European Caucasoids without actinic prurigo, and HLA-DR4 may have an important role in determining expression of this disease.

Adolescent↗

Surfactant replacement therapy in late-stage adult respiratory distress syndrome.

In four adult patients with late-stage acute respiratory distress syndrome (ARDS), a single dose of the artificial surfactant ALEC was given by intrabronchial instillation. There was no sustained clinical improvement, but bronchoalveolar lavage measurements indicated that phosphatidylcholine (PC) at 24 h after treatment had increased up to 4.4 fold and phosphatidylglycerol up to 34.7 fold. However, PC relative to total phospholipid remained below normal, and protein contamination relative to PC remained above normal. Thus, therapeutic formulations and regimens to achieve greater and more sustained supplementation of PC may be required in patients with late-stage ARDS.

Adolescent↗

The human myocardial two-dimensional gel protein database: update 1994.

An updated human heart protein two-dimensional electrophoresis (2-DE) database is presented. The database, which contains some 1388 protein spots characterised in terms of M(r) and pI, has been analysed further by Western immunoblotting and protein sequencing. From a total of 103 protein spots analysed, 49 have been identified by immunoblotting and 32 have been identified by protein sequencing. A further six proteins have tentatively been assigned by comparison with the human heart 2-DE protein database of Jungblut et al. (Electrophoresis) 1994, 15, 685-607). This database is being used in studies of alterations in protein expression in the diseased and transplanted human heart.

Amino Acid Sequence↗

Contrasting population structure from nuclear intron sequences and mtDNA of humpback whales.

Powerful analyses of population structure require information from multiple genetic loci. To help develop a molecular toolbox for obtaining this information, we have designed universal oligonucleotide primers that span conserved intron-exon junctions in a wide variety of animal phyla. We test the utility of exon-primed, intron-crossing amplifications by analyzing the variability of actin intron sequences from humpback, blue, and bowhead whales and comparing the results with mitochondrial DNA (mtDNA) haplotype data. Humpback actin introns fall into two major clades that exist in different frequencies in different oceanic populations. It is surprising that Hawaii and California populations, which are very distinct in mtDNAs, are similar in actin intron alleles. This discrepancy between mtDNA and nuclear DNA results may be due either to differences in genetic drift in mitochondrial and nuclear genes or to preferential movement of males, which do not transmit mtDNA to offspring, between separate breeding grounds. Opposing mtDNA and nuclear DNA results can help clarify otherwise hidden patterns of structure in natural populations.

Animals↗

Hierarchical structure of mitochondrial DNA gene flow among humpback whales Megaptera novaeangliae, world-wide.

The genetic structure of humpback whale populations and subpopulation divisions is described by restriction fragment length analysis of the mitochondrial (mt) DNA from samples of 230 whales collected by biopsy darting in 11 seasonal habitats representing six subpopulations, or 'stocks', world-wide. The hierarchical structure of mtDNA haplotype diversity among population subdivisions is described using the analysis of molecular variance (AMOVA) procedure, the analysis of gene identity, and the genealogical relationship of haplotypes as constructed by parsimony analysis and distance clustering. These analyses revealed: (i) significant partitioning of world-wide genetic variation among oceanic populations, among subpopulations or 'stocks' within oceanic populations and among seasonal habitats within stocks; (ii) fixed categorical segregation of haplotypes on the south-eastern Alaska and central California feeding grounds of the North Pacific; (iii) support for the division of the North Pacific population into a central stock which feeds in Alaska and winters in Hawaii, and an eastern or 'American' stock which feeds along the coast of California and winters near Mexico; (iv) evidence of genetic heterogeneity within the Gulf of Maine feeding grounds and among the sampled feeding and breeding grounds of the western North Atlantic; and (v) support for the historical division between the Group IV (Western Australia) and Group V (eastern Australia, New Zealand and Tonga) stocks in the Southern Oceans. Overall, our results demonstrate a striking degree of genetic structure both within and between oceanic populations of humpback whales, despite the nearly unlimited migratory potential of this species. We suggest that the humpback whale is a suitable demographic and genetic model for the management of less tractable species of baleen whales and for the general study of gene flow among long-lived, mobile vertebrates in the marine ecosystem.

Animals↗