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Biomedical subjects

M Beckett

Publications and source records attributed to M Beckett.

At least 19 recordsLinked to original sources

The new consultant survey 2005.

BACKGROUND: Consultants in emergency medicine have to deal with a wide range of problems, many of which they will not have encountered during their training. One way to assess the adequacy of specialist training is to ask recently appointed consultants whether or not they feel adequately prepared for their role. METHODS: A questionnaire was sent out to 60 newly appointed consultants in emergency medicine in January and February 2005 and the results analysed. RESULTS: Many respondents feel that there should be greater emphasis on acquiring clinical skills, partly by greater consultant supervision and partly by providing more experience of anaesthetics and intensive care. New consultants also feel inadequately prepared for their management responsibilities, and this is a source of great stress. CONCLUSIONS: Specialist training in emergency medicine needs to pay more attention to the acquisition of clinical skills and to preparation for management responsibility.

Attitude of Health Personnel↗

The significance of a defect on DMSA scan in children with renal transplants.

Since December 1995, pediatric renal transplant recipients in our unit have received a DMSA scan as soon as possible post-transplant in order to provide a baseline for comparison in the event of subsequent complications. We retrospectively reviewed the case notes and DMSA scans of the 45 patients who underwent a scan within 9 wk of their transplant to see if pre or peri-transplant factors or post-transplant complications were associated with defects on scanning. Forty percentage of scans had defects. The presence of defects was not associated with potential predisposing factors such as patient or donor age, cadaveric or live donation, cold ischemia time, multiple donor vessels, the use of non-heart beating donors, the mean time to scan, the serum creatinine, or the presence of structural renal tract anomalies predisposing to UTI. However, 87% of patients had complications before the scan, including UTI, rejection, acute tubular necrosis, transplant biopsy and drug toxicity. Children with no clinical complications had a significantly reduced risk of a defect (p = 0.035), while biopsy was associated with the presence of defects (p = 0.0034). Twenty patients had one or more follow up DMSA scans: one patient developed a new focal defect. In conclusion, renal transplant defects are frequently found on DMSA scanning even early after transplantation and are non-specifically associated with many different complications.

Adolescent↗

Recovery from pH 6.38: lactic acidosis complicated by hypothermia.

Survival after extreme arterial acidosis is uncommon. A case of metformin induced lactic acidosis is described where the presenting pH was 6.38 exacerbated by hypothermia (29 degrees C). Increased anion gap acidosis, its varied aetiology, potential reversibility, and the role of hypothermia are discussed. Early liaison with a medical toxicology unit is recommended when this rare condition is suspected.

Acidosis, Lactic↗

Diffusion of ideas about personal hygiene and contamination in poor countries: evidence from Guatemala.

In this paper, we explore the diffusion of beliefs pertaining to the causes of childhood diarrhea in rural Guatemala. The analysis focuses on the importance of interpersonal and impersonal contacts as conduits for information and norms related to hygiene and contamination. Estimates from multivariate models reveal that there is evidence of a diffusion process through social contacts, primarily through interpersonal ones. The analysis also identifies striking differences between (1) the diffusion process related to hygiene (e.g. dirtiness) and that related to contamination (e.g. pathogens); and (2) beliefs about the causes of diarrheal illness among children in general and those among respondents' own children.

Adolescent↗

Antenatal hepatitis B screening - is there a need for a national policy?

Routine antenatal testing for hepatitis B carriage with maternal consent was introduced at the Rotunda in January 1998. The uptake of testing has been excellent; 99.98% of women presenting for antenatal care accepted hepatitis B (HBV) screening in the 30-months from January 1998 through June 2000. The prevalence of HBV carriage was 0.35% (58 pregnancies of 16,222 tested) increasing from 0.25% in 1998 (16 of 6227) to 0.45% in the first six months of 2000 (16 of 3484). Fifty-five women had 58 pregnancies (three women had two pregnancies). Two of these were e-antigen positive. HBV carrier status was previously unknown in 48 (87%). Two additional women had acute HBV infection in pregnancy. Forty-five infants have been born to mothers included in this screening programme. Audit of infant outcome reveals excellent compliance with immunisation and follow-up: 29 (64%) have completed the 3 dose HBV vaccination schedule to date. Thirteen infants (31%) are still attending; three are lost to follow-up including one whose family has emigrated. Routine antenatal screening for hepatitis B carriage is cost-effective and should be considered a standard of care in maternity practice.

Carrier State↗

Do health interview surveys yield reliable data on chronic illness among older respondents?

Previous research evaluating quality of health interview survey data has generally relied upon comparisons of household interview data with medical records or other external sources of information. However, "gold standards" are not always satisfactory or available. This paper illustrates an alternative approach to the evaluation of data quality-examination of the reliability of reports of chronic conditions in longitudinal surveys. The data come from national samples of older Americans (First National Health and Nutrition Examination Survey Epidemiologic Followup Study, 1971-1975, 1982-1984, 1986) and older Taiwanese (Survey of Health and Living Status of the Elderly, 1989, 1993, 1996). The results show that, among respondents who reported a chronic condition at a given interview, the likelihood that the condition was acknowledged at the subsequent interview was higher for hypertension and diabetes than for arthritis and stroke. Low levels of consistency for stroke appear to result partly from the poor wording of questions. In Taiwan, younger, more educated persons and those experiencing severe conditions were somewhat more likely to acknowledge the condition at follow-up compared with their respective counterparts. Women and persons of high cognitive status in the United States and respondents in both countries who used a proxy to report the occurrence of a stroke were also more likely to acknowledge conditions at follow-up.

Adult↗

A mentorship scheme for senior house officers.

Many junior doctors are unsure as to how their aspirations and developing abilities will match up to the demands of specialty training. They need sensitive and realistic guidance if they are to make the right career choice in a highly competitive market.

Humans↗

Converging health inequalities in later life--an artifact of mortality selection.

An emergent issue in the health inequalities debate is how socioeconomic status (SES) and physical health relate over the life course. Many studies indicate that the SES-health relationship diminishes in later life. The present research tests the hypothesis that this convergence in health inequalities is an artifact of mortality selection, which biases downwards the "true" association between SES and health in later life. By including respondents who had subsequently died or were loss-to-followup into the analysis, I assess the sensitivity of the age-specific association between education and health to sample selection processes. I study U.S. adults followed for approximately ten years using the NHANES I Epidemiologic Followup Study. Results based on the surviving sample are robust to the inclusion of people selected out of the sample due to mortality or attrition. Sample selection biases do not appear to explain the convergence in health inequalities in late life.

Adult↗

Poloxamine 1107 sealing of radiopermeabilized erythrocyte membranes.

PURPOSE: Lipid peroxidation-mediated permeabilization of cell membranes following intense ionizing irradiation is well documented. This form of membrane radiopermeabilization leads to rapid exhaustion of cellular high-energy compounds, resulting in the acute onset of cellular necrosis. Strategies to reverse the process of necrosis and preserve cell viability require membrane sealing. This report documents the relative efficacy of Poloxamine 1107, a non-ionic surfactant, compared with other polymers, in sealing radiopermeabilized cell membranes. MATERIALS AND METHODS: Isolated erythrocytes were exposed to 600 Gy 60Co irradiation at a dose rate of 1.3 Gy/s. Different polymer compounds were added 10 min later to the irradiated cell suspensions. At 2 h later the haemoglobin content in the supernatants was determined spectrophotometrically. RESULTS: Compared with the non-treated irradiated control, Poloxamine 1107 significantly reduced the leakage of haemoglobin from irradiated erythrocytes. Poloxamer 188 and dextran at equal concentrations had no significant reverse effect on the irradiation-mediated increased membrane permeability. The amount of haemoglobin released from irradiated erythrocytes was inversely related to the Poloxamine 1107 concentration. CONCLUSIONS: This study demonstrates the capability of Poloxamine 1107 to seal radiopermeabilized cell membranes. Thus, surfactants such as Poloxamine 1107 might be useful as a therapeutic agent in the treatment of high-dose radiation injuries since cellular necrosis due to metabolic exhaustion following radiopermeabilization of their membranes might be prevented.

Cell Membrane Permeability↗

Xrcc3 is required for assembly of Rad51 complexes in vivo.

Rad51 is a member of a family of eukaryotic proteins related to the bacterial recombinational repair protein RecA. Rad51 protein localizes to multiple subnuclear foci in Chinese hamster ovary cells. Subnuclear Rad51 foci are induced by ionizing radiation or the DNA cross-linking agent cisplatin. Formation of these foci is likely to reflect assembly of a multimeric form of Rad51 that promotes DNA repair. Formation of damage-induced Rad51 foci does not occur in the Chinese hamster ovary cell line irs1SF, which is sensitive to DNA damaging agents. The Rad51 focus formation defect of irs1SF cells is corrected by a construct that encodes the repair protein Xrcc3. Xrcc3 is a human homolog of Rad51 previously isolated by virtue of its ability to correct the radiation sensitivity of irs1SF cells. Changes in the steady state level of Rad51 protein do not account for the irs1SF defect nor do they account for the appearance of foci following DNA damage. These results suggest that Xrcc3 is required for the assembly or stabilization of a multimeric form of Rad51 during DNA repair. Cell lines defective in two different components of DNA protein kinase formed Rad51 foci in response to damage, indicating DNA protein kinase is not required for damaged-induced mobilization of Rad51.

Animals↗

p53 expression induces apoptosis in hippocampal pyramidal neuron cultures.

The tumor suppressor gene p53 has been implicated in the induction of apoptosis in dividing cells. We now show that overexpression of p53 using an adenoviral vector in cultured rat hippocampal pyramidal neurons causes widespread neuronal death with features typical of apoptosis. p53 overexpression did not induce p21, bax, or mdm2 in neurons. X-irradiation of hippocampal neurons induced p53 immunoreactivity and cell death associated with features typical of apoptosis. Overexpression of a constitutively active nonphosphorylatable form of the retinoblastoma gene product blocked x-irradiation-induced neuronal death. However, overexpression of the cyclin-dependent kinase inhibitor p21 did not. Treatment of neurons with transforming growth factor-beta1 protected them from x-irradiation. These results are consistent with a role for p53 in nerve cell death that is distinct from its actions relating to cell cycle arrest.

Animals↗

Conservative surgery and adjuvant radiation therapy in the management of adult soft tissue sarcoma of the extremities: clinical and radiobiological results.

PURPOSE: The outcome of adult patients with soft tissue sarcoma of the extremities treated with conservative surgery and adjuvant irradiation was evaluated to (a) determine the appropriate treatment volume and radiation dosage in the postoperative setting, and (b) correlate in vitro radiobiological parameters obtained prior to therapy with clinical outcome. METHODS AND MATERIALS: Sixty-four consecutive adult patients with soft tissue sarcoma of the extremities (40 lower, 24 upper) who underwent conservative surgery and adjuvant irradiation 7 preoperative, 50 postoperative, 7 perioperative) between 1978 and 1991 were reviewed. The initial radiation field margin surrounding the tumor bed/scar was retrospectively analyzed in all postoperative patients. Initial field margins were < 5 cm in 12 patients, 5-9.9 cm in 32 and > or = 10 cm in 6. Patients with negative pathological margins were initially treated with traditional postoperative doses (64-66 Gy); however, in later years the postoperative dose was reduced to 60 Gy. Thirteen cell lines were established prior to definite therapy, and radiobiological parameters (multitarget and linear-quadratic) were obtained and correlated with outcome. RESULTS: Postoperative patients treated with an initial field margin of < 5 cm had a 5-year local control of 30.4% vs. 93.2% in patients treated with an initial margin of > or = 5 cm (p = 0.0003). Five-year local control rates were similar in patients treated with initial field margins of 5-9.9 cm (91.6%) compared with those treated with > or = 10 cm margins (100%) (p = 0.49). While postoperative patients receiving < 60 Gy had a worse local control than those receiving > or = 60 Gy (p = 0.08), no difference was seen in local control between patients receiving less than traditional postoperative doses (60-63.9 Gy) (74.4% vs. those receiving 64-66 Gy (87.0%) (p = 0.5). The local control of patients treated in the later years of the study, with strict attention to surgical and radiotherapeutic technique, was 87.6%. Severe late sequelae were more frequent in patients treated with doses > or = 63 Gy compared to patients treated with lower doses (23.1% vs. 0%) (p < 0.05). Mean values for Do, alpha, beta, D, n and SF2 obtained from the 13 cell lines were 115.7, 0.66, 0.029, 2.15, 0.262, respectively. Four of the 13 cell lines established prior to therapy ultimately failed locally. The radiobiological parameters of these cell lines were similar to the other nine cell lines in terms of radiosensitivity. CONCLUSIONS: Our data confirm the importance of maintaining an initial field margin of at least 5 cm around the tumor bed/scar in the postoperative setting. No benefit was seen with the use of margins > or = 10 cm. In addition, patients undergoing wide local excision with negative margins can be treated with lower than traditional postoperative doses (60 Gy) without compromising local control and with fewer chronic sequelae. Finally, it does not appear that inherent tumor cell sensitivity is a major determinant of local failure following radiation therapy and conservative surgery in soft tissue sarcoma.

Adolescent↗

p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines.

The molecular basis of tumor response to therapeutic radiation is poorly understood. Recent evidence suggests the p53 tumor suppressor gene may be involved in production of the G1 arrest seen following DNA damage by X-irradiation. It has further been proposed that tumor cells lacking the p53 checkpoint function are likely to be more sensitive to cell killing by X-irradiation because these cells enter S phase despite unrepaired DNA damage. We tested the hypothesis that tumor cells with p53 mutations are more radiosensitive by correlating the in vitro surviving fraction at 2 Gy with the mutational status of 24 head and neck squamous cell cancer cell lines. p53 mutations were present in 15 of 24 (63%) of tumors; all were homozygous changes occurring within exons 5-9. The surviving fraction at 2 Gy for the group with mutations was 0.568 compared to 0.507 for tumors without mutations (P = 0.28, Mann-Whitney test). Furthermore, no association between radiosensitivity and mutational type, codon location, or predicted amino acid alteration was noted. Our data do not support the hypothesis that p53 gene alteration predisposes tumor cells to increased cell killing via radiation.

Carcinoma, Squamous Cell↗

Phosphorous metabolite and cell cycle kinetic response of two human squamous cell carcinomas to radiation.

Phosphorous metabolism and cell cycle phase kinetics in response to radiation of two perfused human squamous cell carcinoma cell lines, SQ20B (radioresistant) and SQ38 (relatively radiosensitive), embedded in both basement membrane (Matrigel) and agarose gel threads were studied. The findings for these human cancer cells in response to 2- and 50-Gy irradiation are as follows. (a) Well perfused pure cancer cells (both SQ20B and SQ38) in both proliferative (cells embedded in Matrigel) and static (cells embedded in agarose threads) states did not show significant alteration in either phosphorous bioenergetics or membrane metabolites at 24 and 48 h after irradiation, although a large fraction of the population was clonogenically impaired. Previously reported, sensitively detected, metabolite alterations in response to radiation in rodent and human tumors in situ were not seen in these homogeneous cancer cell populations. (b) The radiosensitive squamous cell carcinoma cell lines SQ38 exhibited G1 block (from 54.38 +/- 1.40% in control to 73.93 +/- 1.01% after irradiation; mean +/ SD) in response to low-dose 2-Gy irradiation and G2 block (from 12.98 +/- 2.15% in control to 25.6 +/- 3.15% after irradiation) in response to high-dose 50-Gy irradiation, while the radioresistant cell line SQ20B showed only conventional G2 block in response to both doses. The differential cell cycle phase response may indicate the difference in radioresistance. (c) The membrane metabolites (including phosphomonoesters and phosphodiesters) and phosphocreatine gradually increased from the early passages to late passages, suggesting that cell proliferation rates were increasing as the cells adapted to tissue culture. The results suggest that the radiation-induced metabolite changes observed in solid tumors in situ may not be a direct response to interim changes within the cancer cells but, rather, a consequence of radiation damage either to the vasculature or to other host-mediated factors.

Animals↗