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Biomedical subjects

L Parker

Publications and source records attributed to L Parker.

At least 145 records · Page 8Linked to original sources
PubMed1993

Genotoxicity of three pyridine compounds to L5178Y mouse lymphoma cells.

The L5178Y mouse lymphoma assay was used to examine the potential mutagenicity of three halogenated pyridine compounds. Position effects of the halogen moiety and the role of metabolic activation were analyzed based on induced mutant frequency, gross chromosome aberrations, and micronuclei. Without activation, 2-chloropyridine, 3-chloropyridine, and 2-chloro-5-trifluoromethylpyridine produced a small increase in mutant frequency; only the 2-chloropyridine activity was significantly increased with activation. All three compounds were also clastogenic as demonstrated by increases in chromosome aberrations and micronuclei (except for 2-chloro-5-trifluoromethylpyridine which did not induce micronuclei either with or without activation).

Animals↗
PubMed1993

Natural history of sleep disordered breathing in community dwelling elderly.

Mild sleep disordered breathing is very common in the elderly, but little is known about the course of the disorder over time. Twenty-four elderly people from a population-based study were recorded three times over an 8.5-year period. There were no significant changes in either apnea index or in respiratory disturbance index (RDI) over time, even when controlled for body mass index. For most subjects, there was great variability over time in the number of respiratory disturbances. The sensitivity of RDI > or = 15 at visit 1 predicting RDI > or = 15 at visit 3 was only 20%. The predictive value was 50%. Sleep disordered breathing measured at a single point in time is rather weakly predictive of the severity of breathing disorder 4-8 years later.

Aged↗
PubMed1993

Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age.

The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.

Creatinine↗
PubMed1993

Cancer in young people in the north of England, 1968-85: analysis by census wards.

OBJECTIVE: To determine whether the seeming excess of childhood leukaemia and lymphoma identified in Seascale, Cumbria, UK, remains unusual when put into a wider context. DESIGN: Analysis of cancer incidence by geographical area. SETTING: The north of England including the Northern and North Western Regional Health Authority regions and the Southport and South Sefton districts of the Mersey Regional Health Authority. SUBJECTS: Altogether 6686 cases of malignant disease in people under 25 years old. MEASUREMENTS AND MAIN RESULTS: Cases of cancer diagnosed before their 25th birthday between January 1968 and December 1985 identified from three regional cancer registries were allocated to a census ward on the basis of 'usual place of residence'. Population data were derived from the 1971 and 1981 censuses, and the cancer incidence was calculated for each ward. Of the 6686 cases, there were 1035 cases of acute lymphoblastic leukaemia and 361 of non-Hodgkins lymphoma. Wards were ranked by cancer incidence and Poisson probability, using different population bases. Seascale ward is the most highly ranked ward for acute lymphoblastic leukaemia for the time periods 1968-85 or 1968-76. It is not the most highly ranked for non-Hodgkins lymphoma. However, combining acute lymphoblastic leukaemia and non-Hodgkins lymphoma incidence gives an even more extreme position for Seascale. The most extreme Poisson probability for any of the analyses was that for brain tumours in the electoral ward of Ashton St Michael, Tameside (p = 0.000009). CONCLUSION: The incidence of acute lymphoblastic leukaemia and non-Hodgkins lymphoma in the Seascale ward remains high when put into a wider context. For other cancers there are wards with even more extreme Poisson probability values.

Adolescent↗
PubMed1993

Mammalian bombesin as a hormone in ovine pregnancy: ontogeny, origin, and molecular forms.

Mammalian gastrin-releasing peptides (GRP) are present in female reproductive tissues and stimulate uterine contraction and DNA synthesis in the endometrium. We set out to establish whether the GRP were likely to play a role in fetal development by measuring the fetal and maternal plasma concentrations in chronically cannulated fetal sheep from 115 days gestation to term (145 days) and for 18 days after parturition. Placental fluids and fetal urine were also obtained. In a separate series of animals, uterine, placental, and fetal gut and lung tissues were collected. Samples were extracted in acid and assayed by radioimmunoassay, and molecular forms were characterized by high-performance liquid chromatography. GRP were present in the decidua (> 10 pmol/g), as well as placental, uterine, lung, and gastrointestinal tissues (all < 6 pmol/g). Fetal and maternal plasma GRP were elevated compared with nonpregnant ewes, falling sharply after parturition. Placental fluids and urine also contained GRP (80-410 fmol/ml). The main molecular form in all tissues and fluids examined coeluted with porcine GRP-(18-27). GRP immunoreactivity was primarily localized to epithelial cells of the decidua. These data suggest that plasma GRP is probably derived from the decidua and may play a role as a circulating hormone in ovine fetal and uterine development.

Animals↗
PubMed1992

Screening for neuroblastoma in the north of England.

OBJECTIVE: To determine the feasibility of establishing a system of screening for neuroblastoma. DESIGN: Prospective study of mass screening in four clearly defined geographical areas. SETTING: Four health districts of the Northern region of England. SUBJECTS: 20,829 babies aged 6 months, 92% of target population. INTERVENTIONS: Collection of urine on filter paper for analysis of content of homovanillic and vanillylmandelic acid in relation to urinary creatinine concentrations. MAIN OUTCOME MEASURES: Derivation of reference range. Identification of babies with homovanillic or vanillylmandelic acid > 3 SD above the mean (positive cases). Investigation of positive cases for evidence of neuroblastoma. RESULTS: The upper limit of normal (3 SD above the mean) for vanillylmandelic acid was 15 mumol/mmol creatinine and for homovanillic acid 24 mumol/mmol creatinine. Of the 20,829 babies screened, 2537 (12.2%) required a second sample to be taken because the first sample was inadequate. Of these, 527 (2.5%) provided a liquid urine specimen and 10 (0.04%) had positive results for neuroblastoma. Two of them had neuroblastoma (true positives) and eight did not (false positives). A further three children from the cohort were subsequently found to have neuroblastoma; they had raised homovanillic acid or vanillylmandelic acid values, or both, but screened negative at 6 months. CONCLUSIONS: Screening for neuroblastoma is possible in the health care system of the United Kingdom. Evaluation of the efficacy of screening in reducing the mortality from neuroblastoma requires a controlled trial.

Creatinine↗
PubMed1992

Purification and characterization of a thermostable proteinase isolated from Thermus sp. strain Rt41A.

Thermus sp. strain Rt41A produces an extracellular thermostable alkaline proteinase. The enzyme has a high isoelectric point (10.25-10.5) which can be exploited in purification by using cation-exchange chromatography. The proteinase was purified to homogeneity and has a molecular mass of 32.5 kDa by SDS/PAGE. It is a glycoprotein, containing 0.7% carbohydrate as glucose equivalents, and has four half-cystine residues present as two disulphide bonds. Maximum proteolytic activity was observed at pH 8.0 against azocasein and greater than 75% of this activity was retained in the pH range 7.0-10.0. Substrate inhibition was observed with casein and azocasein. The enzyme was stable in the pH range 5.0-10.0 and maximum activity, in a 10-min assay, was observed at 90 degrees C with 5 mM CaCl2 present. No loss of activity was observed after 24 h at 70 degrees C and the half-lives at 80 degrees C and 90 degrees C were 13.5 h and 20 min, respectively. Removal of Ca2+ reduced the temperature for maximum proteolytic activity against azocasein to 60 degrees C and the half-life at 70 degrees C was 2.85 min. The enzyme was stable at low and high ionic strength and in the presence of denaturing reagents and organic solvents. Rt41A proteinase cleaved a number of synthetic amino acid p-nitrophenol esters, the kinetic data indicating that small aliphatic or aromatic amino acids were the preferred residue at the P1 position. The kinetic data for the hydrolysis of a number of peptide p-nitroanilide substrates are also reported. Primary cleavage of the oxidized insulin B chain occurred at sites where the P1' amino acid was aromatic. Minor cleavage sites (24 h incubation) were for amino acids with aliphatic side chains at the P1' position. The esterase and insulin cleavage data indicate the specificity is similar for both the P1 and P1' sites.

Amino Acid Sequence↗
PubMed1992

Hemihypertrophy as possible sign of renal cell carcinoma.

In infants and children there is a well-recognized association of hemihypertrophy with visceral malignancies, including those of the kidney as well as benign renal disorders. As a result of our report on an adult with segmental hemihypertrophy and renal cell carcinoma, we suggest that if this combination represents an association similar to that found in children, a radiographic-urologic evaluation is needed to diagnose renal neoplasms at an early stage, and to disclose the presence of treatable benign renal disease.

Carcinoma, Renal Cell↗
PubMed1992

Food aversions: taste reactivity responses elicited by lithium-paired food.

The taste reactivity (TR) test was employed to measure the orofacial, somatic and consummatory CRs elicited by a lithium-paired food. Hungry rats were presented chocolate chips followed immediately by an injection of lithium chloride (CS+ group) or saline (CSc group). During the TR test, the rats' behavioral responses to the chocolate chips were videorecorded. The results demonstrated that rats in the CS+ group did not consume the lithium-paired food, but demonstrated the aversive TR response pattern of chain rubbing, paw treading, and gaping.

Animals↗
PubMed1992

Unexpected adverse reactions during a clinical trial in rural west Africa.

Ribavirin has been used widely in various clinical trials, without significant adverse effects beyond reversible, mild anemia. Since 1978 intravenous ribavirin has been used to treat Lassa fever in a remote area of Eastern Sierra Leone, West Africa. In March 1991, brief episodes of rigors in patients receiving ribavirin were reported. An immediate investigation found that 27/93 patients (29%) had records in 1990/91 of at least one episode, the strongest association being with survival of Lassa fever (P = 0.0001). The occurrence or number of rigors in an individual patient was unassociated with sex, age, weight, volume of loading dose, cumulative dose, administration of other drugs, use of intravenous lines or heparin traps. In a review of 12 years of ribavirin administration, 74/2117 injections sampled (3.5%) were associated with a record of rigors. Most occurred before 08.00 h (P less than 0.0001), between 0 and 30 min after injection, lasted 2-45 min, and clustered towards the end of the treatment course (P less than 0.0001). There was no association with drug lot or individual vials. Drug was being given as a bolus (less than 1 min). Since slowing the infusion rate, no further episodes have been reported. Epidemiologic techniques are important tools in rapid assessment of unexpected events particularly when conducting trials in remote locations.

Humans↗
PubMed1992

Relapsing polychondritis: a case diagnosed by direct immunofluorescence and coexisting with pseudocyst of the auricle.

A case of relapsing polychondritis with perichondrial IgG and C3, dermoepidermal IgG, and a coexisting pseudocyst of the auricle is reported. The use of direct immunofluorescence testing in establishing a diagnosis of relapsing polychondritis and the expected findings are reviewed. In some cases direct immunofluorescence may allow a diagnosis of relapsing polychondritis before clinical criteria or a routine histologic evaluation suggests a definite diagnosis.

Aged↗
PubMed1992

Screening for neuroblastoma in the northern region of England. Laboratory aspects.

Our pilot study for neuroblastoma screening started in 1986. The study has progressed through several phases, with use of several analytical methods to a procedure based primarily on the use of automated gas chromatography mass spectrometry. The northern region of England has a relatively static population of approximately 3.5 million, with an annual birth rate of 41,000. The region consists of 16 administrative health districts. In 4 years, we have screened 20,829 infants from four health districts. In this program, we screen all children at 6 months of age. A urine sample is collected on filter paper by a health visitor, either at the time of the infant's routine clinic visit or during the health visitor's follow-up visit at home. In the laboratory, the sample is dried and processed for analysis of homovanillic acid (HVA) and vanillylmandelic acid (VMA), using a benchtop Hewlett Packard gas chromatograph mass spectrometer. The results are related to the creatinine content of the urine. Using cut-off limits of 39 micrograms/mg of creatinine for HVA and 25 micrograms/mg of creatinine for VMA, 2,537 infants (12.2%) required a second paper sample and 527 infants (2.5%) were observed with a liquid urine collection. Of these, the conditions of nine infants with elevated levels of HVA or VMA were investigated clinically for the possible presence of neuroblastoma. Two infants were found to have neuroblastoma; the other seven showed no evidence of tumor. In addition, there were three children who, when screened at 6 months of age, had normal levels of HVA and VMA but in whom neuroblastoma subsequently developed.

Biomarkers, Tumor↗
PubMed1992

A pilot study of screening for neuroblastoma in the north of England.

A pilot study has been carried out to assess the feasibility of screening for neuroblastoma in 6-month-old infants in the north of England. A total of 20,829 infants were screened. Two true-positive cases were found, along with eight false-positive and three false-negative cases. It was shown that the concentrations of catecholamine metabolites in the urine are dependent on the creatinine content; centiles have been established to allow this relationship to be taken into account. Five of the eight false-positive cases would have been correctly assessed as normal if the new centiles had been used. Preliminary results lend support to the need for a well-designed study of neuroblastoma screening to be carried out, with death from this disease as the only end point.

England↗
PubMed1992

Poor prognosis neuroblastoma: is screening the answer?

Neuroblastoma is one of the most common solid tumours of childhood and is unique amongst paediatric cancers in that it results in the urinary excretion of catecholamine metabolites which are easily measured in spot urine samples and so is a condition for which screening may be considered. The continuing poor prognosis associated with late stage disease has stimulated great interest in this proposition. The Japanese have been undertaking pioneering studies of such screening since 1974 and since 1985, all 6 months old babies have been offered screening. Preliminary data would appear to suggest that screening is effective in greatly improving the survival of children with neuroblastoma. However there are difficulties associated with the interpretation of survival data since screening undoubtedly results in the detection of cases which would otherwise have remained 'silent', and the well known problems of lead-time and length-time bias complicate matters still further. The time is not yet ready for universal implementation of screening and further investigation is required.

Adult↗