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Biomedical subjects

E Birks

Publications and source records attributed to E Birks.

12 recordsLinked to original sources
PubMed2006

Sensitization following LVAD implantation using leucodepleted blood is not due to HLA antibodies.

Implantation of left ventricular assist devices (LVAD) is associated with HLA antibody sensitization. The objective of this study was to determine the specificity of antibodies produced by LVAD recipients using a combination of ELISA, Luminex and microcytotoxicity assays. Fifty-one LVAD patients were studied, from 44 to 838 days post-implantation. No patient developed HLA antibodies, although 24 produced IgG antibodies detectable in both ELISA and Luminex assays. These antibodies manifest as positive reactions with class I and class II wells of the ELISA and also blank wells. In Luminex assays, they produce high MFI readings with the negative control beads. Antibodies were detected 18 to 228 days after implantation. This reactivity was found to be directed against bovine serum albumin (BSA), commonly used to block non-specific binding in ELISA and Luminex assays; absorption of sera with BSA-coated beads completely abrogated reactivity in all solid phase assays, but did not eliminate anti-HLA antibodies in control sera. Ten of the 24 patients have proceeded to transplantation, with a 1-year graft survival of 69%. In conclusion, it appears that implantation of LVADS disrupts immunoregulatory pathways leading to production of anti-albumin antibodies. These can be misinterpreted as anti-HLA antibodies in solid phase assays.

Adult↗
PubMed2000

Upregulation of the Bcl-2 family of proteins in end stage heart failure.

OBJECTIVES: To elucidate the pattern of expression of four members of the Bcl-2 family of proteins and to correlate this with terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end labelling (TUNEL) and DNA fragmentation. BACKGROUND: Apoptosis has been implicated as a possible mechanism in the development of heart failure. However, the mechanisms involved remain unclear. METHODS: We have studied the expression of four members of the Bcl-2 family that are involved in the regulation of apoptosis and analyzed DNA fragmentation as a marker of apoptosis and as a biochemical criterion to distinguish between apoptosis and necrosis in dilated cardiomyopathy (DCM), ischemic heart disease (IHD) and normal donors. RESULTS: Western blot analysis and immunocytochemistry of the proapoptotic and antiapoptotic Bcl-2 proteins demonstrated significantly higher levels of all these proteins in the diseased groups compared with normal donors. Additionally, Bax was significantly higher in the IHD group compared with DCM. Terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end labelling analysis demonstrated a significantly higher percentage of TUNEL-positive cells in the diseased groups compared with the control. Genomic DNA extraction of ventricular myocardial tissue showed no demonstrable DNA laddering for any of the groups. CONCLUSIONS: The significant increases in the levels of the proapoptotic proteins Bak and Bax and the higher percentage of TUNEL-positive cells in both diseased groups suggests the presence of ongoing apoptosis. However, increases in the antiapoptotic proteins, Bcl-2 and Bcl-xL, suggest a possible concomitant, compensatory antiapoptotic mechanism in patients with heart failure.

Adult↗
PubMed2000

Risk factors for failure to thrive: a population-based survey.

AIM: To identify whether differences exist between failure to thrive children and controls in either demographic characteristics or parental rating of their eating and other behaviour. METHODS: As part of an intervention study, 97 children with failure to thrive were identified by population screening and received a standardized assessment by their health visitor at a median age of 15.1 months. This included standard questions to parents concerning their perception of their child's feeding history and behaviour. Their responses were compared with the parents of 28 normally growing children aged 16-18 months, systematically sampled from the same district. RESULTS: Cases had fallen through a mean of 1.69 weight standard deviation score and were markedly underweight for height. The case families had similar levels of deprivation, both to controls and city norms, and only four showed evidence of major neglect. Failure to thrive children had significantly more infancy feeding problems and were introduced to solids and finger foods later than controls; they were significantly more often described as variable eaters, undemanding and shy and less often as hungry. Cases liked most foods, but significantly less so than controls. CONCLUSIONS: This suggests that the role of deprivation and neglect has been overstated and that undemanding behaviour, low appetite and poor feeding skills may contribute to the onset and persistence of failure to thrive.

Failure to Thrive↗
PubMed1998

Effect of community based management in failure to thrive: randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a health visitor led intervention for failure to thrive in children under 2 years old. DESIGN: Controlled trial, randomised by primary care practice. SETTING: Newcastle upon Tyne health district. INTERVENTION: Structured health visitor management, with dietetic, paediatric, and social work input as required. SUBJECTS: 229 children (120 in intervention practices and 109 in control practices) were identified as failing to thrive by population screening during the first 2 years of life. Follow up was by home visit of a research nurse and review of the childrens' records at age 3 years. MAIN OUTCOME MEASURES: Follow up weight and height and number of routinely collected weights. RESULTS: 95 of the 97 families offered intervention completed at least the initial assessment. At follow up, 187 (82%) records were reviewed, and these suggested that 15 (16%) controls were lost to follow up immediately after the screening weight was taken compared with only one child in the intervention group. In the 134 (58%) families who consented to home visits, children in the intervention group were significantly heavier and taller and were reported to have better appetites than childen in the control group, although both groups were equally satisfied by the services they had received. When the children were last weighed, 91 (76%) in the intervention group had recovered from their failure to thrive compared with 60 (55%) in the control group (P<0.001). CONCLUSION: In failure to thrive, health visitor intervention, with limited specialist support, can significantly improve growth compared with conventional management.

Body Height↗
PubMed1998

New chart to evaluate weight faltering.

A new chart was designed to aid accurate identification of weight faltering and failure to thrive. It provides guidance on the lower limits of expected weight gain for children, whatever their initial centile position. The chart's theoretical basis, the process of its construction, and its evaluation are described in this paper. Evaluation was by a self completion questionnaire, where respondents answered questions about a range of standardised growth patterns, plotted on old and new charts. Forty five health visitors, 28 general practitioner principals and registrars, and nine community paediatricians provided 328 chart ratings. These showed that the new format significantly increased the proportion of correctly rated charts (old: 45 (28%); new: 82 (51%)), with the greatest impact in severe cases. This suggests that the new chart improves the precision of judgments made about weight gain in infancy.

Child, Preschool↗
PubMed1997

Pulmonary autograft versus homograft replacement of the aortic valve: a prospective randomized trial.

BACKGROUND: Pulmonary autografts offer many theoretical advantages. However, the operation is complex, may interfere with right ventricular and pulmonary outflow function, and requires a longer operative time than does the homograft operation. The effects of these potential disadvantages are unknown. METHODS: To clarify these issues we randomized 70 patients undergoing aortic valve replacement to an aortic homograft group (group A = 37 patients; 53%; 34 male, 3 female) or a pulmonary autograft group (group B = 33 patients; 47%; 28 male, 5 female). Ages varied from 12 to 65 years (mean 39 +/- 15 years) for group A and from 3 to 54 years (mean 29 +/- 15 years) for group B (p = not significant). Eleven patients in group A (30%) and eight in group B (24%) had previous aortic valve surgery. All patients were operated on by the same surgeon. The mean cardiopulmonary bypass time was 113 +/- 29 minutes (range 66 to 175 minutes) for group A and 151 +/- 31 minutes (range 115 to 226 minutes) for group B (p < 0.002). Mean aortic crossclamp time was 85 +/- 19 minutes (range 45 to 140 minutes) for group A and 109 +/- 20 minutes (range 74 to 164 minutes) for group B (p = 0.02). In 32 patients (86.5%) the aortic homograft was implanted as a root with coronary reimplantation. All pulmonary autografts were implanted as a root. RESULTS: No early or late deaths had occurred in this series at a mean follow-up time of 16 months (range 3 to 21 months). Two patients (one in each group) required reexploration for bleeding. No statistically significant differences were observed between the two groups with regard to ventilatory support (group A, mean 10 +/- 8.5 hours; group B, mean 29 +/- 85 hours), total blood loss (group A, mean 471 +/- 347 ml; group B, mean 543 +/- 404 ml), intensive care unit stay (group A, mean 1.2 +/- 0.6 days; group B, mean 2 +/- 3.7 days), and hospital stay (group A, mean 9.5 = 3.2 days; group B, mean 12 +/- 6 days). Postoperatively, all patients are in New York Heart Association class I (93%) or II (7%) (p = not significant). Ejection fraction for the two groups did not change significantly over the follow-up period. Left ventricular mass and diastolic diameter showed progressive regression, with no apparent difference between the two treatment groups to date. Echocardiographic evaluation of aortic valve function at 6 months showed good valve function in all patients with no evidence of aortic regurgitation in 80% of both groups. In group B the right ventricular outflow gradient was below 15 mm Hg over the follow-up period. Holter monitoring, available only in 44 patients (63%), showed most of the arrhythmias to be grade 0 to 1 of the modified Lown grading system. CONCLUSION: Although the pulmonary autograft requires a significantly longer operating time, this does not seem to affect early and medium-term outcome when compared with results obtained with aortic homografts. Continued patient evaluation is warranted, particularly with regard to evidence of valve degeneration and right ventricular function and arrhythmias in the long term.

Adolescent↗
PubMed1996

Intrinsic tone and distensibility of in vitro and in situ cat pulmonary arteries.

This study was designed to determine the in vitro and in situ diameter vs pressure relationship of 200- to 1,200-microns diameter pulmonary arteries in the cat. Diameter vs pressure relationships of these arteries were obtained using two methods, microscopic observation of in vitro cannulated and pressurized arteries and X-ray angiography of in situ arteries. Both in vitro and in situ arteries were studied first under normal conditions and then after reducing tone with Ca(2+)-free solution (in vitro) or papaverine (in situ). In vitro arteries commonly increased their tone in response to elevated transmural pressure, and in some cases, the diameter actually decreased as pressure increased. This behavior was not observed in the in situ arteries. The major difference between in vitro and in situ arteries was that when the in vitro arteries were relaxed, the slope of the diameter vs pressure curves increased, whereas the slope was not altered significantly by relaxation of the in situ arteries. This difference is emphasized by the increased distensibility with relaxation of the in vitro arteries but the decreased distensibility with relaxation of the in situ arteries. The results of this study suggest that, at least in the cat, small pulmonary arteries possess a mechanism that is dormant in the in situ environment within the normal lung. However, the potential for pressure-induced constriction may be unmasked by changing the vessel history and/or environment. Extrapolating results obtained from in vitro pulmonary arteries to the in situ situation should therefore be done with caution. Studies directed at what factors contribute to differences in the responses of in vitro and in situ arteries might help in understanding pulmonary vascular pathophysiology.

Angiography↗
PubMed1993

Anti-HIV-1 activity and cellular pharmacology of various analogs of gossypol.

We previously reported that the racemic mixture and both enantiomers of gossypol inhibit the replication of human immunodeficiency virus-type 1 (HIV-1) (Lin et al., Antimicrob Agents Chemother 33: 2149-2151, 1989). The present study evaluates the activities of a variety of analogs of gossypol as well as a few non-gossypol analogs. Compounds 2, 3, 10, and 13 were slightly more inhibitory than (-)-gossypol to the replication of HIV-1 in cell culture. Compounds 4 and 8 were cytotoxic to human peripheral blood monocyte (PBM) cells, and compounds 2 and 3 were cytotoxic to Vero cells but not PBM cells. The effects of the two enantiomers of gossypol on the cell volume and migration of H9 cells through the cell cycle were evaluated during 72 hr of incubation. The (-)-enantiomer of gossypol was more toxic to H9 cells than the (+)-enantiomer of gossypol as evidenced by cell destruction. Prior to cell destruction, there appeared to be no significant effect on cell cycle distribution with either enantiomer.

Animals↗
PubMed1993

Empirical and rational approaches for development of inhibitors of the human immunodeficiency virus--HIV-1.

The human immunodeficiency virus, HIV-1, is generally accepted to be responsible for AIDS. It is imperative that all approaches, empirical and rational, be taken for development of a drug for therapy of this disease. These approaches are discussed, with emphasis on the direction being pursued in our laboratory. Empirically, we found 3'-deoxy-2',3'-didehydrothymidine, a compound first synthesized for potential anticancer activity by J. Horwitz in the 1960s, to be a potent inhibitor of HIV-1. It is now in Phase II/III clinical trials. We have also synthesized several 2,5'-anhydro pyrimidine nucleoside analogs, which have interesting chemical and biological properties. We have evaluated a natural product, gossypol and synthesized various derivatives for anti-HIV-1 activity, but none were appreciably more inhibitory than the parent compound. More recently, we have taken the rational approach and synthesized a boron-modified tetrapeptide, Ac-Thr-Leu-Asn-boro-Phe, which corresponds to the COOH-terminal of the Phe-Pro scissle bond of the gag/pol gene polyprotein product. Potent inhibition of the HIV-1 encoded protease was observed. These approaches and findings will be discussed.

Amino Acid Sequence↗
PubMed1977

Protective action of selenium against mercury in northern creek chubs.

We found selenium dixoide an effective antagonist to the toxic effects of mercuric chloride in the northern creek chub (Semotilus atromaculatus). Selenium pretreatment increased the whole body accumulation of mercury at lower environmental Hg concentrations. It decreased mercury accumulation in survivors at higher, acutely toxic concentrations.

Animals↗