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Biomedical subjects

C McKay

Publications and source records attributed to C McKay.

At least 19 recordsLinked to original sources
PubMed2004

Urinary trypsinogen activation peptide as a marker of severe acute pancreatitis.

BACKGROUND: Trypsinogen activation peptide (TAP) may be an early marker of severe pancreatitis. Previous studies have included all patients with organ failure in the group with severe pancreatitis, although patients with transient organ failure may have a good prognosis. The aim of this study was to determine the value of urinary TAP estimation for prediction of severity of acute pancreatitis, and to validate use of several markers of prediction of severity against a new, stringent definition of severity. METHODS: Patients with acute pancreatitis were recruited within 24 h of onset of symptoms. Urine and blood samples were collected for 24 h, and Acute Physiology And Chronic Health Evaluation (APACHE) II (24 h), Ranson (48 h) and Glasgow (48 h) scores were calculated. Severe acute pancreatitis was defined by the presence of a local complication or the presence of organ failure for more than 48 h. RESULTS: Urinary TAP levels were significantly greater in patients with severe pancreatitis than in those with mild disease during the first 36 h of admission. The highest of three estimations of TAP in the first 24 h was as effective as APACHE II at 24 h in predicting severity. At 24 h after admission, urinary TAP was better than C-reactive protein (CRP) in predicting severity. The combination of TAP and CRP at 24 h allowed identification of high- and low-risk groups. The new definition of severity excluded 24 of 190 patients with transient organ failure; none of these patients died. CONCLUSION: Use of TAP improved early prediction of the severity of acute pancreatitis. Organ failure that resolves within 48 h does not signify a severe attack of acute pancreatitis.

APACHE↗
PubMed2003

Estimation of fruit and vegetable intake using a two-item dietary questionnaire: a potential tool for primary health care workers.

BACKGROUND AND AIM: High fruit and vegetable intake is associated with health benefits for cancer and cardiovascular disease. An increase is therefore integral in recommendations for the prevention of chronic disease. However, measuring intake requires either extensive dietary assessment or the measurement of specific bio-markers which is neither cheap nor feasible for the routine assessment of an individual's diet in a community or primary care setting. Within the context of a study evaluating a dietary counselling programme to increase fruit and vegetable intake our aim was to assess the use of a simple tool to estimate fruit and vegetable intake. METHODS AND RESULTS: We studied associations between bio-markers [plasma ascorbic acid, beta-carotene and alpha-tocopherol 24-hour urinary potassium excretion] and a two-item fruit and vegetable consumption questionnaire in 271 subjects (105 men and 166 women), aged 18 to 70 years. After controlling for age, sex, vitamin supplement use, smoking and body mass, those reporting a daily intake of > or = 5 portions of fruit and vegetables had higher potassium excretion (difference 15.6 [95% confidence interval: 6.2 to 25.0] mmol/24 h), urinary potassium/creatinine ratio (1.2 [0.5 to 2.0]) and plasma vitamin C (10.0 [-0.9 to 20.8] mumol/L) than those reporting < or = 2.5 portions per day. beta-carotene (p = 0.04), vitamin C (p = 0.01) and potassium excretion (p < 0.001) were associated with fruit rather than vegetable intake. The two-item questionnaire had high specificity; over 3/4 of participants who reported low intake also had bio-markers below the upper third of the distribution. CONCLUSION: Self report of fruit and vegetable intake through a simple questionnaire is confirmed by bio-markers for those eating less than five portions of fruit and vegetables a day. Although the tool is amenable to improvements for the detection of vegetable portions, it may prove useful for monitoring dietary preventive approaches in primary care without the use of invasive and costly biochemical measurements.

Adolescent↗
PubMed2001

Biogenic methane, hydrogen escape, and the irreversible oxidation of early Earth.

The low O2 content of the Archean atmosphere implies that methane should have been present at levels approximately 10(2) to 10(3) parts per million volume (ppmv) (compared with 1.7 ppmv today) given a plausible biogenic source. CH4 is favored as the greenhouse gas that countered the lower luminosity of the early Sun. But abundant CH4 implies that hydrogen escapes to space (upward arrow space) orders of magnitude faster than today. Such reductant loss oxidizes the Earth. Photosynthesis splits water into O2 and H, and methanogenesis transfers the H into CH4. Hydrogen escape after CH4 photolysis, therefore, causes a net gain of oxygen [CO2 + 2H2O --> CH4 + 2O2 --> CO2 + O2 + 4H(upward arrow space)]. Expected irreversible oxidation (approximately 10(12) to 10(13) moles oxygen per year) may help explain how Earth's surface environment became irreversibly oxidized.

Atmosphere↗
PubMed2001

The distal region and receptor tyrosines of the Epo receptor are non-essential for in vivo erythropoiesis.

The erythropoietin receptor (EpoR) is required for the proliferation and survival of committed erythroid lineage cells. Previous studies have utilized receptor mutations to show the requirement for the distal half of the cytoplasmic domain of the EpoR and receptor tyrosines for activation of signaling pathways potentially critical to Epo function. To extend these studies to in vivo erythropoiesis, we have created two mutant strains of mice. One strain (H) contains a truncation of the distal half of the cytoplasmic domain, while the second strain (HM) contains the same truncation as well as the mutation of the residual tyrosine (Y(343)) to a phenylalanine. Strikingly, both strains of mice are viable, with only slight alterations in constitutive erythropoiesis or in in vitro assays of red cell lineage function. Challenging H mutant mice with continuous injections of Epo results in an erythrocytosis that is not seen in HM mice. The results demonstrate that neither the distal region nor receptor tyrosines are essential for in vivo EpoR function, but contribute to receptor function in a subtle manner.

Animals↗
PubMed2001

A retrospective study of clubhouse-based transitional employment.

This study of clubhouse-based transitional employment (TE) examined the ability of demographic data, diagnosis, and data on TE participation to predict TE tenure and a one-year competitive employment outcome following TE among clubhouse members. Baseline data on 138 club members who participated in TE over a 6-year period were retrospectively retrieved from a computerized database and written records. Most of the jobs held by members were maintenance or production jobs; members' average tenure on TE was 131.26 days. Older members, those with a longer club membership before their last TE job, and those working more days per week had longer average tenure on TE. Average tenure was unrelated to the severity of disability. Forty-two (30.4%) members obtained competitive employment in the one year following their last TE job. Members who worked more total hours on TE were more likely to obtain competitive employment. While aspects of the TE experience predict the move to competitive employment, further studies are needed.

Adult↗
PubMed2001

Jak3 selectively regulates Bax and Bcl-2 expression to promote T-cell development.

Jak3-deficient mice display vastly reduced numbers of lymphoid cells. Thymocytes and peripheral T cells from Jak3-deficient mice have a high apoptotic index, suggesting that Jak3 provides survival signals. Here we report that Jak3 regulates T lymphopoiesis at least in part through its selective regulation of Bax and Bcl-2. Jak3-deficient thymocytes express elevated levels of Bax and reduced levels of Bcl-2 relative to those in wild-type littermates. Notably, up-regulation of Bax in Jak3-deficient T cells is physiologically relevant, as Jak3 Bax double-null mice have marked increases in thymocyte and peripheral T-cell numbers. Rescue of T lymphopoiesis by Bax loss was selective, as mice deficient in Jak3 plus p53 or in Jak3 plus Fas remained lymphopenic. However, Bax loss failed to restore proper ratios of peripheral CD4/CD8 T cells, which are abnormally high in Jak3-null mice. Transplantation into Jak3-deficient mice of Jak3-null bone marrow transduced with a Bcl-2-expressing retrovirus also improved peripheral T-cell numbers and restored the ratio of peripheral CD4/CD8 T cells to wild-type levels. The data support the concepts that Jak kinases regulate cell survival through their selective and cell context-dependent regulation of pro- and antiapoptotic Bcl-2 family proteins and that Bax and Bcl-2 play distinct roles in T-cell development.

Animals↗
PubMed2001

Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis.

BACKGROUND: Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate. FINDINGS: Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups. INTERPRETATION: The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis

Acute Disease↗
PubMed2000

Objectivity and accuracy of mammogram interpretation using the BI-RADS final assessment categories in 40- to 49-year-old women.

To determine if use of the five final assessment categories of the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS) improved objectivity or accuracy of mammographic evaluation in 40- to 49-year-old women, fifty mammograms of 40- to 49-year-old women that were obtained at a tertiary referral teaching hospital were classified according to those five final assessment categories. The mammograms were blinded to six American Osteopathic Board of Radiology-certified radiologists who were asked to classify each mammogram within the five final BI-RADS categories based on the mediolateral oblique and craniocaudal views presented. No history was allowed. Use of the BI-RADS five final assessment categories provided moderate interobserver objectivity, moderately high agreement among the radiologists' interpretation (reliability), and moderate accuracy of interpretation (validity) when compared to criterion. Moderate interobserver reliability and accuracy has been previously identified; however, no scientific review of the BI-RADS five final assessment categories in 40- to 49-year-old females was discovered in the current literature. No overall improvement of objectivity or accuracy was demonstrated using the five final assessment categories of the BI-RADS lexicon in 40- to 49-year-old women.

Adult↗
PubMed1999

SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality.

SOCS1 is an SH2-containing protein that is primarily expressed in thymocytes in a cytokine- and T cell receptor-independent manner. SOCS1 deletion causes perinatal lethality with death by 2-3 weeks. During this period thymic changes include a loss of cellularity and a switch from predominantly CD4+ CD8+ to single positive cells. Peripheral T cells express activation antigens and proliferate to IL-2 in the absence of anti-CD3. In addition, IFNgamma is present in the serum. Reconstitution of the lymphoid lineage of JAK3-deficient mice with SOCS1-deficient stem cells recapitulates the lethality and T cell alterations. Introducing a RAG2 or IFNgamma deficiency eliminates lethality. The results demonstrate that lymphocytes are critical to SOCS1-associated perinatal lethality and implicate SOCS1 in lymphocyte differentiation or regulation.

Age Factors↗
PubMed1999

SOCS3 is essential in the regulation of fetal liver erythropoiesis.

SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling. During embryonic development, SOCS3 is highly expressed in erythroid lineage cells and is Epo independent. Transgene-mediated expression blocks fetal erythropoiesis, resulting in embryonic lethality. SOCS3 deletion results in an embryonic lethality at 12-16 days associated with marked erythrocytosis. Moreover, the in vitro proliferative capacity of progenitors is greatly increased. SOCS3-deficient fetal liver stem cells can reconstitute hematopoiesis in lethally irradiated adults, indicating that its absence does not disturb bone marrow erythropoiesis. Reconstitution of lymphoid lineages in JAK3-deficient mice also occurs normally. The results demonstrate that SOCS3 is critical in negatively regulating fetal liver hematopoiesis.

Animals↗
PubMed1999

Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells.

Many cytokines activate two highly homologous Stat proteins, 5a and 5b. Mice deficient in both genes lack all growth hormone and prolactin functions but retain functions associated with cytokines such as erythropoietin. Here, we demonstrate that, while lymphoid development is normal, Stat5a/b mutant peripheral T cells are profoundly deficient in proliferation and fail to undergo cell cycle progression or to express genes controlling cell cycle progression. In addition, the mice lack NK cells, develop splenomegaly, and have T cells with an activated phenotype, phenotypes seen in IL-2 receptor beta chain-deficient mice. These phenotypes are not seen in mice lacking Stat5a or Stat5b alone. The results demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2 signaling in T cells.

Animals↗
PubMed1998

Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses.

A variety of cytokines mediate the activation of Janus protein tyrosine kinases (Jaks). The Jaks then phosphorylate cellular substrates, including members of the signal transducers and activators of transcription (Stat) family of transcription factors. Among the Stats, the two highly related proteins, Stat5a and Stat5b, are activated by a variety of cytokines. To assess the role of the Stat5 proteins, mutant mice were derived that have the genes deleted individually or together. The phenotypes of the mice demonstrate an essential, and often redundant, role for the two Stat5 proteins in a spectrum of physiological responses associated with growth hormone and prolactin. Conversely, the responses to a variety of cytokines that activate the Stat5 proteins, including erythropoietin, are largely unaffected.

Animals↗
PubMed1998

Automated tracking of left ventricular wall thickening with intracardiac echocardiography.

OBJECTIVE: We developed and evaluated a new method to automatically measure regional left ventricular wall thickening by analyzing the radiofrequency backscatter signal from an intracardiac echocardiographic catheter. METHODS: We inserted 10-MHz echocardiographic catheters in 11 dogs. Wall thickness was perturbed by altering loading conditions and inotropic state. The backscatter signal from a single selected radial scan line was digitized. An automated algorithm identified the digitized endocardial and epicardial signals, tracked them throughout the cardiac cycle, and plotted the spatial difference over time. Pressure-thickness loops were generated. RESULTS: End-systolic and end-diastolic thickness and percent wall thickening from the unedited, unsmoothed signals compared favorably with independent manual analysis of transthoracic echocardiographic images of the same region: r = 0.89 for wall thickness and 0.81 for systolic thickening. CONCLUSION: The backscatter signal from an intracardiac echocardiographic device can be analyzed automatically to continuously assess regional left ventricular wall thickening and generate pressure-thickness loops.

Animals↗
PubMed1998

Soil temperatures and stability of ice-cemented ground in the McMurdo Dry Valleys, Antarctica.

Year-round temperature measurements at 1600 m elevation during 1994 in the Asgard Range Antarctica, indicate that the mean annual frost point of the ice-cemented ground, 25 cm below the surface, is -21.7 +/- 0.2 degrees C and the mean annual frost point of the atmosphere is -27.5 +/- 1.0 degrees C. The corresponding mean annual temperatures are -24.9 degrees C and -23.3 degrees C. These results imply that there is a net flux of water vapour from the ice to the atmosphere resulting in a recession of the ice-cemented ground by about 0.4-0.6 mm yr-1. The level of the ice-cemented permafrost is about 12 cm below the level of dry permafrost. The summer air temperatures would have to increase about 7 degrees C for thawing temperatures to just reach the top of the subsurface ice. Either subsurface ice at this location is evaporating over time or there are sporadic processes that recharge the ice and maintain equilibrium over long timescales.

Antarctic Regions↗
PubMed1998

Intracardiac echocardiography: computerized detection of left ventricular borders.

A semi-automated method for two- and three-dimensional analysis of intracardiac echocardiography (ICE) images and image sequences is reported based on detection of epicardial and endocardial borders using graph searching. The border detection method was applied to 50 ICE images acquired in vivo in five dogs and to 108 images in 16 volumetric ICE image sequences from eight cadaveric pig hearts. The ICE images from the in vivo study showed good correlation between computer-detected and observer-defined left ventricular (LV) cavity areas and epicardial areas (r = 0.99, y = 0.98x + 0.43 [cm2]; r = 0.99, y = 0.98x + 1.11 [cm2]; respectively). In the cadaveric hearts, the LV volumes were determined with the volume measurement error of 7.6 +/- 7.7% and 11.3 +/- 11.2% for the aortic valve and mitral valve image sequences, respectively. Our method facilitates an accurate and computationally efficient approach for the quantitative assessment of ICE image data in 2D and 3D.

Animals↗
PubMed1997

A randomized, controlled trial of octreotide in the management of patients with acute pancreatitis.

CONCLUSION: In this study, octreotide was not found to be of benefit in the treatment of acute pancreatitis. BACKGROUND: Somatostatin and its long-acting analog octreotide have both been proposed for the treatment of patients with acute pancreatitis, but neither agent has been adequately assessed in patients with severe attacks. METHODS: Fifty-eight patients with moderate or severe acute pancreatitis who were admitted to hospitals within the west of Scotland over an 18-mo period were randomized to receive octreotide, 40 micrograms/h, by continuous i.v. infusion for 5 d, or placebo in addition to standard supportive therapy. RESULTS: There was no significant difference in the incidence of complications (54% octreotide group and 40% placebo group) or mortality (octreotide group 18%; placebo group 20%).

Acute Disease↗