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Biomedical subjects

J Earl

Publications and source records attributed to J Earl.

At least 19 recordsLinked to original sources
PubMed2005

Anticipation in familial pancreatic cancer.

BACKGROUND: Previous studies of anticipation in familial pancreatic cancer have been small and subject to ascertainment bias. Our aim was to determine evidence for anticipation in a large number of European families. PATIENTS AND METHODS: A total of 1223 individuals at risk from 106 families (264 affected individuals) were investigated. Generation G3 was defined as the latest generation that included any individual aged over 39 years; preceding generations were then defined as G2 and G1. RESULTS: With 80 affected child-parent pairs, the children died a median (interquartile range) of 10 (7, 14) years earlier. The median (interquartile range) age of death from pancreatic cancer was 70 (59, 77), 64 (57, 69), and 49 (44, 56) years for G1, G2, and G3, respectively. These indications of anticipation could be the result of bias. Truncation of Kaplan-Meier analysis to a 60 year period to correct for follow up time bias and a matched test statistic indicated significant anticipation (p=0.002 and p<0.001). To minimise bias further, an iterative analysis to predict cancer numbers was developed. No single risk category could be applied that accurately predicted cancer cases in every generation. Using three risk categories (low with no pancreatic cancer in earlier generations, high with a single earlier generation, and very high where two preceding generations were affected), incidence was estimated without significant error. Anticipation was independent of smoking. CONCLUSION: This study provides the first strong evidence for anticipation in familial pancreatic cancer and must be considered in genetic counselling and the commencement of secondary screening for pancreatic cancer.

Adult↗
PubMed2004

Potential health risks of complementary alternative medicines in cancer patients.

Many cancer patients use complementary alternative medicines (CAMs) but may not be aware of the potential risks. There are no studies quantifying such risks, but there is some evidence of patient risk from case reports in the literature. A cross-sectional survey of patients attending the outpatient department at a specialist cancer centre was carried out to establish a pattern of herbal remedy or supplement use and to identify potential adverse side effects or drug interactions with conventional medicines. If potential risks were identified, a health warning was issued by a pharmacist. A total of 318 patients participated in the study. Of these, 164 (51.6%) took CAMs, and 133 different combinations were recorded. Of these, 10.4% only took herbal remedies, 42.1% only supplements and 47.6% a combination of both. In all, 18 (11.0%) reported supplements in higher than recommended doses. Health warnings were issued to 20 (12.2%) patients. Most warnings concerned echinacea in patients with lymphoma. Further warnings were issued for cod liver/fish oil, evening primrose oil, gingko, garlic, ginseng, kava kava and beta-carotene. In conclusion, medical practitioners need to be able to identify the potential risks of CAMs. Equally, patients should be encouraged to disclose their use. Also, more research is needed to quantify the actual health risks.

Complementary Therapies↗
PubMed2004

Role of tetrahydrobiopterin in adrenocorticotropic hormone-induced hypertension in the rat.

Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is characterized by nitric oxide deficiency. Tetrahydrobiopterin (BH4) is an essential cofactor for the enzyme nitric oxide synthase and glucocorticoids have been reported to reduce cytokine-induced BH4 production. Accordingly we hypothesized that ACTH-induced hypertension would be reversed by BH4 supplementation. Male Sprague-Dawley rats (n = 33) were treated with BH4 in vehicle (10 mg/kg/day i.p.) or vehicle alone (5 mg/kg/day i.p. of ascorbic acid in 4 mM HCl) for 10 days. ACTH (0.2 mg/kg s.c.) or saline daily injection was started 2 days after BH4 or vehicle treatment and continued for 8 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. Treatment with HCl, ascorbic acid or BH4 alone had no effect on SBP. In saline treated rats, neither BH4 nor its vehicle modified SBP. In ACTH treated rats, SBP was increased in both BH4 (from 128 +/- 6 to 142 +/- 4 mmHg, T0 to T10, P < 0.0005, one way ANOVA) and vehicle groups (from 127 +/- 3 to 158 +/- 7 mmHg, T0 to T10, P < 0.001, one way ANOVA). There was no significant difference in SBP between BH4 + ACTH treated and vehicle + ACTH treated rats. Thus, daily injection of BH4 (10 mg/kg i.p.) failed to prevent the development of ACTH-induced hypertension in rat.

Adrenocorticotropic Hormone↗
PubMed2004

The molecular diversity of the methanogenic community in a hypereutrophic freshwater lake determined by PCR-RFLP.

AIMS: To combine database-held sequence information with a programme of experimental molecular ecology to define the methanogenic community of a hypereutrophic lake by a PCR-restriction fragment length polymorphism (RFLP) analysis. METHODS AND RESULTS: Methanogen diversity in a hypereutrophic freshwater lake was analysed using 16S rDNA PCR-RFLP. Database-held 16S rRNA gene sequences for 76 diverse methanogens were analysed for specific restriction sites that permitted unequivocal differentiation of methanogens. Restriction digestion and agarose gel electrophoresis of the 16S rDNA from selected methanogen pure cultures generated observed restriction profiles that corroborated the expected patterns. This method was then tested by analysing methanogen diversity in samples obtained over 1 year from sediment and water samples taken from the same sampling site. CONCLUSIONS: Restriction analysis of the 16S rRNA gene sequences from 157 methanogen clones generated from lakewater and sediment samples showed that over 50% were similar to Methanoculleus spp. Furthermore, a total of 16 RFLP types (1-16) were identified, eight of which contained no cultured representative archaeal 16S rRNA gene sequences. SIGNIFICANCE AND IMPACT OF THE STUDY: This RFLP strategy provides a robust and reliable means to rapidly identify methanogens in the environment.

DNA, Bacterial↗
PubMed2003

Analysis of methanogen diversity in a hypereutrophic lake using PCR-RFLP analysis of mcr sequences.

The incidence and diversity of methanogens in Priest Pot, a dynamic and active lake, were monitored by analysing mcrA gene sequences generated from total DNA samples obtained at different times of the year and amplified using the polymerase chain reaction. A number of mcrA clones were analysed by developing an RFLP-based protocol to generate a number of restriction patterns that were assigned to a number of classes. The RFLP patterns for each class were compared with published sequence information for mcrA from cultured methanogens as well as with those from other experimental studies. They could be used to assign tentative identification for some of the Priest Pot clones and also revealed the presence of a number of clones that could not be affiliated to any known methanogens. The limitations of using RFLP profiles of mcrA gene sequences for studying methanogen ecology are discussed.

Bacteria↗
PubMed2000

Warrior midwife.

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Certification↗
PubMed1999

Examination of the metabolic status of rat air pouch inflammatory exudate by high field proton NMR spectroscopy.

High field proton (1H) NMR spectroscopy was employed to investigate the metabolic status of rat air pouch inflammatory exudates obtained subsequent to the induction of inflammation with carrageenan, and the 1H NMR profiles of these fluids were compared and contrasted with those of inflammatory human synovial fluid, rat plasma and human serum. The characteristic biochemical features obtained from 1H NMR analysis of these exudates consisted of (1) substantially elevated levels of lactate (11.40+/-1.46x10-3 mol dm-3 for samples collected at a time point of 24 h post induction) with little or no NMR-detectable glucose, data consistent with a hypoxic environment and consequent anaerobic metabolism in the inflamed air pouch, and (2) high levels of the ketone body 3-d-hydroxybutyrate, providing evidence for an increased utilization of fats for energy by lymphocytes, the predominant leucocytes present in this environment. These phenomena represent a pathological extreme of the abnormal metabolic status of inflammatory human synovial fluids.

Air↗
PubMed1997

Plasma and serum micronutrient concentrations in preschool children.

The plasma concentrations of vitamin A, vitamin E, beta-carotene and serum concentrations of zinc, retinol-binding protein and prealbumin were examined for a random cluster sample, stratified by socioeconomic status, of 467 healthy preschool children. Children were aged 9-62 months; 44% were females. The mean plasma values were: vitamin A, 1.29 micromol l(-1); vitamin E, 18.9 micromol l(-1); and beta-carotene, 0.30 micromol l(-1). The mean serum values were: zinc, 13.9 micromol l(-1); retinol-binding protein, 25.5 mg l(-1); and prealbumin, 186.2 mg l(-1). The mean molar ratio of vitamin A to retinol-binding protein for the study group was 1.10. There were no differences in the mean values of any of the measured micronutrients between the genders. The results of this survey do not indicate that the prevalence of micronutrient deficiency in this preschool population is of public health significance.

Antioxidants↗
PubMed1997

Age-specific reference intervals for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin for Sydney children aged 9-62 months.

Paediatric reference intervals for blood concentrations of certain nutrients are often based on either adult data or are derived from small samples of young children. Biochemical data were obtained from 467 randomly selected, healthy preschool children aged 9-62 months in Sydney, Australia. Data were obtained for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin. Reference intervals based on the 2.5 and 97.5 centiles for age groups 9-23, 24-35, 36-47, 48-62 months and for the total group (9-62 months) were calculated. The 2.5-97.5 centiles for the whole group were: vitamin A, 0.7-1.8 mumol/l (20.05-51.56 micrograms/dl); vitamin E, 8-30 mumol/l (0.34-1.29 mg/dl); beta-carotene, 0.1-1.1 mumol/l (5.4-59.0 micrograms/dl); zinc, 9-19 mumol/l (58.8-124.2 micrograms/dl); retinol-binding protein, 14-36 mg/l; prealbumin, 104-264 mg/l. The reference intervals reported are consistent with the findings of a number of smaller studies and are likely to be an accurate reflection of the true intervals for healthy preschool children in western developed countries.

Aging↗
PubMed1996

Origin of BSE.

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Animals↗
PubMed1994

Vitamin A status in preterm neonates with and without chronic lung disease.

It has been proposed that there is an association between vitamin A (VA) deficiency and the development of chronic lung disease (CLD) in preterm infants. This study was designed to measure the VA status in preterm infants and to compare the results in the group of babies who developed CLD with the group who did not. Vitamin A status was assessed by measuring plasma VA, retinol binding protein (RBP) and the plasma VA:RBP molar ratio in 25 infants of less than 31 weeks gestation during the first 28 days of life. Eleven babies developed CLD and 14 did not. There was no significant difference in plasma VA levels between the CLD and non CLD groups during the first 28 days. The majority of infants had adequate VA status, with a subgroup being deficient.

Chronic Disease↗
PubMed1991

Halothane in children with chronic liver disease.

Exacerbation of pre-existing liver disease after halothane anaesthesia has been reported in adult patients. A prospective study was performed in 38 children with biopsy-proven liver disease to assess the effect of surgery and halothane anaesthesia on liver function. Plasma liver enzyme levels were measured immediately preoperatively and again four to eight days after surgery and halothane anaesthesia. Minor elevations of both AST and ALT occurred in four patients but this was not associated with a clinical deterioration in the patients' postoperative recovery. In the children studied pre-existing liver disease did not predispose to a deterioration of liver function following surgery and halothane anaesthesia.

Adolescent↗
PubMed1991

Biliary excretion of the halothane metabolite trifluoroacetic acid in infants.

In humans the biliary excretion of trifluoroacetic acid, the major halothane metabolite, has not been studied. We investigated the biliary excretion of trifluoroacetic acid in two infants aged five months and two months following halothane anaesthesia for the operation of choledocholithotomy. Bile, urine and faeces were collected continuously for five days after operation and trifluoroacetic acid excretion measured. Estimates of halothane uptake, daily bile flow and the proportion of daily bile flow collected via the T-tube drainage catheter were subject to percentage errors possibly as large as 50%. Of the total trifluoroacetic acid produced from halothane metabolism, it was estimated that 17% in the five-month-old infant and 20% in the two-month infant was excreted in bile. In the five-month-old infant where approximately 80% of the bile produced entered the duodenum in the normal way, no faecal trifluoroacetic acid was detected suggesting an enterohepatic circulation for this metabolite.

Anesthesia, Inhalation↗
PubMed1991

N-Trifluoroacetyl-ethanolamine: a proposed urinary metabolite of halothane: validation and measurement in children.

It has been postulated that trifluoroacetyl chloride, a halothane metabolite, can bind covalently with the phosphatidylethanolamine component of the hepatic cell membrane and cause cell necrosis. Breakdown of the necrotic hepatocyte would release N-trifluoroacetyl-ethanolamine (TFAE) into the serum with subsequent urinary excretion. An original High Performance Liquid Chromatography (HPLC) method for the measurement of TFAE is described. In six children 1% halothane was administered for one hour and the halothane uptake measured. Urinary excretion of TFAE was measured for up to eight days and found to be 0.09 +/- 0.07% or less of the absorbed halothane. In children TFAE is not a major urinary metabolite of halothane.

Anesthesia, Inhalation↗
PubMed1990

Determination of individual bile acids in serum by high performance liquid chromatography.

A high performance liquid chromatographic (HPLC) method for analysis of 4 free and 8 conjugated bile acids in submicromolar quantities in serum is described using precolumn derivatization with 4-bromomethyl-7-methoxycoumarin (BMC) and fluorescence detection. Bile acids were extracted from serum with 0.4 M sodium bicarbonate, adsorbed onto a Sep-Pak C18 cartridge and eluted with methanol. The extract was derivatized with BMC in acetonitrile using 18-crown-6 crown ether as catalyst and the BMC labelled glycine conjugates and free bile acids were analysed using acetonitrile + methanol + water gradient elution and detection at 320/385 nm. Using a novel and simple approach, taurine conjugates were isolated by extracting the dried, derivatized material with water, in contrast to previous methods which required column chromatography cleanup to isolate the taurine conjugates prior to derivatization. The isolated taurine conjugates were then hydrolysed enzymatically, extracted, derivatized and analysed as free-bile acids. Recoveries of individual bile acids varied from 83-96% for free and glycine conjugates and 72-83% for taurine conjugates. Coefficients of variation were in the range of 5.1-12.5%. In addition to the simpler and shorter procedure for taurine conjugates, this method has increased sensitivity over most other procedures and improved HPLC separation for the various bile acids and conjugates with equivalent recovery and reproducibility compared with other published methods.

Bile Acids and Salts↗