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Biomedical subjects

L Parker

Publications and source records attributed to L Parker.

At least 127 records · Page 7Linked to original sources
PubMed1996

Variations by specialty in physician ratings of the appropriateness and necessity of indications for procedures.

The authors compare the appropriateness ratings and mutual influence of panelists from different specialties rating a comprehensive set of indications for six surgical procedures. Nine-member panels rated each procedure: abdominal aortic aneurysm surgery, carotid endarterectomy, cataract surgery, coronary angiography, and coronary artery bypass graft surgery/percutaneous transluminal coronary angioplasty (common panel). Panelists individually rated the appropriateness of indications at home and then discussed and re-rated the indications during a 2-day meeting. Subsequently, they rated the necessity of those indications scored by the group as appropriate. There were 45 panelists, including specialists (either performers of the procedure or members of a related specialty) and primary care providers, all drawn from nominations by their respective specialty societies. Main outcome measures included: individual panelists' mean ratings over all indications, mean change and conformity scores between rounds of ratings, and the percentage of audited actual procedures rated appropriate or necessary. Performers had the highest mean ratings, followed by physicians in related specialties, trailed by primary care providers. One fifth of all actual procedures were for indications rated appropriate by performers and less than appropriate by primary care providers. At the panel meetings, primary care providers and related specialists showed no greater tendency to be influenced by other panelists than did performers. Multispecialty panels provide more divergent viewpoints than panels composed entirely of performers. This divergence means that fewer actual procedures are deemed performed for appropriate or necessary indications.

Angioplasty, Balloon, Coronary↗
PubMed1996

The sex ratio of children in relation to paternal preconceptional radiation dose: a study in Cumbria, northern England.

STUDY OBJECTIVE: To investigate whether the occupational exposure to external ionising radiation of men employed at the Sellafield nuclear installation, West Cumbria, affects the sex of the children they subsequently father. DESIGN: A retrospective cohort study using logistic regression to analyse the sex ratio, in particular in relation to paternal preconceptional irradiation. SETTING AND PARTICIPANTS: The 260,060 singleton births between 1950 and 1989 to mothers resident in Cumbria, north west England. RESULTS: The sex ratio among children of men employed at any time at Sellafield was 1.094 (95% CI: 1.060, 1.128), significantly higher than that among other Cumbrian children, 1.055 (95% CI: 1.046, 1.063). There was an increased sex ratio of 1.396 (95% CI: 1.127, 1.729) in the 345 children whose fathers were estimated from annual dose summaries to have received more than 10 mSv of external radiation in the 90 days preceding conception, but no significant linear trend between sex ratio and 90 day paternal preconceptional dose was found. There was no significant association between sex ratio and the external dose accumulated before the 90 day period preceding conception. CONCLUSIONS: Men employed at Sellafield fathered a greater proportion of boys than would be expected for a Cumbrian population, which may be partly explained by their younger age distribution. A greater effect was observed in the fathers with recorded doses exceeding 10 mSv in the 90 days before conception. While this may reflect a true statistical association, it is also possible that it may be a chance finding due to imprecision in the dose estimates and consequent misclassification.

Adult↗
PubMed1995

Urinary creatinine adjusted reference ranges for homovanillic and vanillylmandelic acid in children and adults.

The relationship between urinary homovanillic acid (HVA), vanillylmandelic acid (VMA) and creatinine is investigated and reference ranges are constructed for HVA and VMA. A total of 769 urine samples were obtained from children and adults. The ratios HVA/creatinine and VMA/creatinine were highly correlated with creatinine concentration; hence, reference to creatinine was found to be an inappropriate adjustment for urinary dilution. An alternative method based upon linear regression is proposed. After allowing for differing levels of creatinine, HVA and VMA were found to be significantly correlated with age, height and weight for individuals aged less than 20 years. In those aged over 20 years, HVA was significantly correlated with weight and VMA with age. Differences between sexes were found in the levels of HVA and VMA, the exception being VMA in the over 20 age group. Reference ranges were constructed for HVA and VMA which are variously dependent upon creatinine, age, sex and weight.

Adolescent↗
PubMed1995

Screening for Wilms' tumour in patients with aniridia, Beckwith syndrome, or hemihypertrophy.

The role of screening for early detection of Wilms' tumour (WT) in patients with aniridia (A), Beckwith-Weidemann syndrome (BWS) and hemihypertrophy (HH) has been explored. Of the 1,622 Wilms' tumour patients registered with the National Childhood Cancer Registry from 1971 to 1991, 41 were recorded as having A, BWS or HH. Twenty-eight of these had their anomaly diagnosed before the WT and 13 had screening procedures carried out, mainly abdominal ultrasound. In 8 patients the screening procedure detected the WT. There was no significant difference in stage distribution or outcome for any of the three subgroups who were not screened, screen-positive or screen-negative. We conclude that regular screening with abdominal ultrasound is not of proven value. Parents should be taught abdominal palpation and advised to seek appropriate advice for untoward symptoms.

Aniridia↗
PubMed1995

Is neuroblastoma screening evaluation needed and feasible?

Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity.

Age Factors↗
PubMed1995

Melanoma tumor-infiltrating lymphocytes derived from four distinct anatomic sites obtained from a single patient: comparison of functional reactivity and melanoma antigen recognition.

Tumor-infiltrating lymphocytes (TILs) were grown from four distinct anatomic sites from a patient with metastatic melanoma. The metastatic sites included a tumor-involved lymph node, a subcutaneous lesion obtained from the chest wall, a portion of bowel, and adrenal gland. TILs grown from each anatomic site over the course of 20 days in the presence of 6,000 IU/ml recombinant interleukin-2 exhibited comparable growth rates. Between days 30 and 45, the TILs were a mixture of CD3+ CD4+ and CD3+ CD8+ lymphocytes expressing the alpha beta form of the T-cell receptor. TILs derived from each anatomic site specifically lysed autologous tumor obtained from all four anatomic sites. In fine specificity analysis, the TILs exhibited human leukocyte antigen (HLA-A2)-restricted lysis of fresh tumor targets and cultured melanoma cell lines. Each TIL recognized a product of the MART-1 gene, and specifically, the monomer peptide MART-1(27-35). Thus lymphocytes reactive with the MART-1 melanoma antigen appeared to be widely distributed in diverse metastases in this patient. This information, along with previous data on the reactivity of multiple patients to this antigen, attests to its dominance in the immune reactivity of humans to melanoma.

Adrenal Gland Neoplasms↗
PubMed1994

Cytokine regulation by platelet-activating factor in a human B cell line.

TNF-alpha is an inflammatory cytokine produced by B cells that also impacts B cell differentiation and Ig secretion. We have investigated the regulation of the TNF-alpha gene in a human B cell line in response to platelet-activating factor (PAF), a potent phospholipid often produced in inflammatory reactions. We report here that PAF increases the RNA levels for the TNF-alpha gene in the human B cell line Ramos. This is mediated by an increase in the transcription rate and a longer half-life of the TNF-alpha transcripts. Induction of the TNF-alpha gene is rapid in these cells and independent of new protein synthesis. Despite increasing RNA for the TNF-alpha gene, PAF increases TNF-alpha protein levels only in the presence of a costimulus, such as PMA. We hypothesize that PAF acts at the transcriptional level to increase TNF-alpha RNA, but a post-transcriptional block acts to regulate protein production. We also report that PAF enhances PMA-induced TNF-alpha production from human peripheral B cells. This increase is maximal at 0.1 microM PAF and is blocked by PAF receptor antagonists. The ability of PAF to modulate cytokine production from human B cells provides further evidence that PAF has a role in B cell biology and suggests it may be important in conditions involving B cell-derived cytokines.

B-Lymphocytes↗
PubMed1994

Cyclosporin A blocks induction of tumor necrosis factor-alpha in human B lymphocytes.

The effects of cyclosporin A (CSP) on tumor necrosis factor-alpha (TNF-alpha) RNA levels and protein production in human B cells and a B cell line were studied. The ability of CSP to block induction of RNA was compared to its inhibition of protein production in response to anti-IgM, phorbol ester (PMA) and platelet-activating factor (PAF). PAF is a phospholipid which has recently been found to activate human B cells. CSP blocks PAF-induced TNF-alpha RNA from the Ramos cell line, as well as inhibiting the enhancement of TNF protein production from both freshly isolated and Ramos B cells. CSP also blocks anti-Ig induced TNF-alpha RNA and protein but does not inhibit PMA-induced TNF-alpha. We conclude that B cells, like T cells, have CSP-independent and CSP-dependent signaling pathways and that PAF signaling is dependent upon a CSP-sensitive factor.

B-Lymphocytes↗
PubMed1994

Do alcohol and lead change the sex ratio?

It has been suggested that exposure to alcohol and lead may decrease testosterone levels in men which in turn may lead to an increase in the proportion of girls among their offspring. This hypothesis is tested on a new dataset of 268,109 children born in Cumbria from 1950-89. From fathers' occupations given on birth certificates, we calculated the sex ratio for offspring of men exposed occupationally to alcohol and lead. We carried out a meta-analysis of the present and previous studies. The results are consistent with the hypothesis that alcohol and lead lower the sex ratio.

Automobile Driving↗
PubMed1994

False positive results in a neuroblastoma screening programme.

Twenty thousand, eight hundred and twenty-nine babies were screened for neuroblastoma at 6 months of age by measuring homovanillic (HVA) and vanillylmandelic (VMA) acid in urine and rationing these to creatinine. Using a "cut off" of the mean + 3 SD, 10 were found to be positive. Two were found on evaluation to have neuroblastoma and in the remaining 8 the raised levels of HVA and/or VMA returned to normal. Only one of the 8 false positive babies was absolutely normal, most having a chronic disorder or illness. Utilising new centiles which relate HVA and VMA to creatinine, only 3 of the 8 would have remained positive, a false positive rate of 0.01%. The false negative rate would have remained unchanged.

Creatinine↗
PubMed1994

Amphetamine-induced modification of quinine palatability: analysis by the taste reactivity test.

The effects of low doses of d-amphetamine (0.25-0.5 mg/kg, IP) on taste reactions elicited by quinine solutions in a 5-10-min taste reactivity test were assessed in a series of three experiments. Amphetamine consistently suppressed aversive reactions elicited by quinine solutions. The results suggest that amphetamine, like morphine, attenuates the aversiveness of the taste of quinine solution.

Animals↗
PubMed1994

Measuring the necessity of medical procedures.

This is a report on the extension of the concept of the appropriateness of a procedure to the necessity, or crucial importance, of that procedure. To state that a procedure is crucial means that withholding the procedure would be deleterious to the patient's health. Appropriateness and necessity ratings for six procedures were obtained using a modified Delphi panel process developed in earlier work. Panels were composed of practicing clinicians who were recognized leaders in their fields. The panels included both performers and nonperformers of the procedure under discussion. For most procedures and panelists, necessity was related to appropriateness, but was distinct from it. The proportion of indications for which the procedure was crucial varied in clinically consistent ways both among and within procedures. However, panelists did not achieve a consensus on necessity. Further research is suggested to refine the method to promote consensus and to validate further the ratings of necessity. In conclusion, necessity ratings can be used together with appropriateness ratings to address not only the overuse of procedures, but also to indicate limited access to care through underuse of procedures.

Angioplasty, Balloon, Coronary↗
PubMed1994

Estrogen-dependent expression of the cystic fibrosis transmembrane regulator gene in a novel uterine epithelial cell line.

We have demonstrated previously the modulation of CFTR expression by estrogen in vivo in the rat uterine epithelium. The purpose of this study was to establish a suitable in vitro system to investigate the regulation of CFTR by steroid hormones. Primary cultures of rat uterine epithelial cells, which showed high levels of CFTR expression in vitro, were infected with an adeno/SV40 virus. One clone, UIT 1.16, which retained the morphology of the primary epithelial cells yet proliferated beyond the life span of the primary culture, was isolated and characterized. Successful immortalization of UIT 1.16 cells was verified by the presence of a band corresponding to the SV40 large T-antigen in western blots, as well as by their ability to proliferate continuously. Transmission electron microscopy studies revealed that these cells maintained the characteristics of a polarized epithelium with well-established membrane domains and specialized intercellular junctions. A high transepithelial electrical resistance was also observed when cells were assayed in modified Ussing chambers. When the basolateral cellular membrane of cells grown in vitrogen-coated filters was permeabilized with nystatin, a forskolin-stimulated Cl- permeability was observed in the apical membrane, similar to that present in other CFTR-expressing epithelial cells. UIT 1.16 cells showed high levels of CFTR expression on northern blots. The expression of CFTR was dependent on the presence of estrogen in the culture medium, since almost undetectable levels of CFTR mRNA were observed when the cells were cultured in medium containing serum depleted of steroid hormones. However, addition of estrogen to this medium prevented the disappearance of CFTR mRNA, confirming estrogen-regulated expression of CFTR in the UIT 1.16 cell line. The newly developed UIT 1.16 cell line provides a valuable model to analyze the regulation of CFTR expression by steroid hormones. Moreover, the cell line could also be used to investigate the role of CFTR in the uterus during the normal female cycle as well as for the study of other uterine epithelial functions and the agents that regulate them.

Adenoviridae↗
PubMed1993

Geographical distribution of preconceptional radiation doses to fathers employed at the Sellafield nuclear installation, West Cumbria.

OBJECTIVE: To examine whether the geographical distribution of births associated with preconceptional exposure of fathers to radiation at the Sellafield nuclear installation is consistent with the suggestion that this exposure explains the excess of childhood lymphoid malignancy in the adjacent village of Seascale. DESIGN: Retrospective birth cohort study. SETTING: Cumbria, West Cumbria health district, and Seascale civil parish. SUBJECTS: The 10,363 children born in Cumbria during 1950-89 to fathers employed at Sellafield. MAIN OUTCOME MEASURES: The doses of external whole body ionising radiation received by fathers at Sellafield in the total time and in the six months before conception of their children; the proportions of the collective doses associated with Seascale and the rest of West Cumbria. RESULTS: 9256 children were born to fathers who had been exposed to radiation before the child's conception. Of these, 7318 had fathers who were exposed in the six months before conception. Overall 7% (38 person-Sv) of the collective total preconceptional dose and 7% (3 person-Sv) of the collective dose for the six months before conception were associated with children born in Seascale. Of all the children whose fathers worked at Sellafield, 842 (8%) were born in Seascale. The mean individual doses before conception were consistently lower in Seascale than in the rest of West Cumbria. CONCLUSIONS: The distribution of the paternal preconceptional radiation dose is statistically incompatible with this exposure providing a causal explanation for the cluster of childhood leukaemias in Seascale.

Adult↗