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Biomedical subjects

J Pickering

Publications and source records attributed to J Pickering.

At least 19 recordsLinked to original sources
PubMed2001

"Folate before pregnancy": the impact on women and health professionals of a population-based health promotion campaign in South Australia.

OBJECTIVES: To evaluate a South Australian campaign to promote and implement knowledge that taking adequate folate/folic acid in the periconceptional period can reduce the risk of having a baby with a neural tube defect. DESIGN AND SETTING: The campaign, conducted in October 1994--August 1995, targeted women of reproductive age and health professionals. Evaluation was by computer-assisted telephone interviews undertaken by random dialling throughout the State before and after the campaign, and by self-administered questionnaires to health professionals and women in the postnatal period. PARTICIPANTS: Women of reproductive age and four groups of health professionals. MAIN OUTCOME MEASURES: Knowledge about folate, folate-rich foods and the periconceptional period; participation of health professionals in advising women about folate; use of periconceptional folic acid supplements; sales of folic acid tablets; and prevalence of neural tube defects. RESULTS: Significant increases in knowledge about folate followed the campaign. Health professionals and women in the postnatal period had higher initial levels of knowledge about folate, which also increased significantly. The proportions of women taking periconceptional folic acid supplements, and of health professionals advising women planning a pregnancy about folate, also increased significantly, and folic acid tablet sales doubled. Total prevalence of neural tube defects declined between 1966 and 1999 from a baseline of 2.0 per 1,000 births to 1.1 per 1,000 births (Poisson regression, P= 0.03; average decline of 1.0% per year). CONCLUSIONS: A short educational campaign with a limited budget ($40,000) can promote folate successfully, but alternative strategies such as food fortification are likely to be needed to achieve adequate periconceptional folate intake for a very high proportion of women.

Adolescent↗
PubMed2001

Platelet tests in the prediction of myocardial infarction and ischaemic stroke: evidence from the Caerphilly Prospective Study.

A platelet test that is predictive of myocardial infarction (MI) and/or stroke would enable the targeting of anti-platelet drugs towards high-risk patients. The predictive power of several platelet tests for MI and for stroke was examined in 2000 older men in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The tests were: aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP); aggregation to ADP in whole blood measured using an impedance method and a test of platelet aggregation induced in whole blood by high-shear flow. Around 200 MIs and 100 ischaemic strokes occurred during a 10-year follow-up. Neither primary nor secondary aggregation in PRP was predictive of MI. However, the fifth of men in whom the primary response to ADP was least, showed the highest risk of a subsequent stroke [relative odds (RO) 1.64; 95% confidence interval (CI) 1.12-2.43]. Aggregation in whole blood was not predictive of MI but, again, the fifth of men with the least platelet response showed the highest stroke incidence (RO 1.79; 95% CI 1.06-3.00). Retention of platelets in the high-shear test was not predictive of either event.

Adenosine Diphosphate↗
PubMed2001

Cognitive function and blood rheology: results from the Caerphilly cohort of older men.

OBJECTIVES: Vascular lesions are important contributors to cerebral disease, yet relatively little work has been done on relationships between haematological factors and cognitive function. We have explored these relationships in the Caerphilly cohort of older men. DESIGN: The development of vascular disease and the decline in cognitive function are being studied in a cohort of older men in Caerphilly, South Wales, UK. We have recorded a range of life-style, dietary, lipid, haematological and rheological factors which are, or may be, predictive of vascular disease. We have examined the relationships between these and both incident myocardial infarction and stroke, and identified factors relevant to cognitive function. SETTING: A community-based study based upon a representative population sample of older men. We collected data for the study from around 90% of the survivors of the original cohort. SUBJECTS: 2154 men who were aged 55-69 years at the time blood was taken for the haematological tests and cognitive function was tested. MAIN OUTCOME MEASURES: We present data from the AH4 test of general cognitive performance and from choice reaction time, a test of vigilance. RESULTS: There is a U-shaped relationship between haematocrit and cognitive function, the best cognitive function scores occurring at a mean haematocrit of 0.46. The relationship is significant for the choice reaction time (P < 0.05). The relationship between haematocrit and the AH4 test score is also curvilinear, but it is not significant. Plasma viscosity showed strong and robust relationships, with significantly better cognitive performance and faster reaction times at lower levels of viscosity (both relationships P < 0.001). Plasma fibrinogen concentration did not show any significant relationships with cognitive function. All these relationships are present, but are much weaker, with rheological tests that had been carried out 5 years before the cognitive testing. CONCLUSIONS: Blood rheology, as estimated by both haematocrit and plasma viscosity, is a significant determinant of cognitive function in older men. On the other hand, the thrombotic potential of blood, as indicated by fibrinogen level, shows no significant relationships. The relationships with rheology seem to be direct, presumably through blood flow at the time of testing, rather than through underlying long-term disease processes.

Aged↗
PubMed2000

An audit of the vaccination and antibiotic prophylaxis practices amongst patients splenectomised in Lothian.

OBJECTIVE: To evaluate current post-splenectomy immunisation and antibiotic prophylaxis practices amongst patients splenectomised in Lothian between 1st January 1989 and 31st December 1997. DESIGN: Retrospective cross-sectional study of the general practitioners of patients recorded as having had a splenectomy operation. SETTING: Lothian Health Board (population 771,000). SUBJECTS: Asplenic patients recorded on Scottish Morbidity Records as having had a splenectomy in Lothian between 1st January 1989 and 31st December 1997. RESULTS: Eighty point six percent of the patients were vaccinated against Streptococcus pneumoniae, 65.9% were vaccinated against Haemophilus influenzae, and 48.2% were vaccinated against Neisseria meningitidis; 74.8% of patients were being prescribed long-term antibiotic prophylaxis. However, only 37.4% were both vaccinated and prescribed prophylaxis as recommended, in Department of Health guidelines. CONCLUSIONS: The vaccination levels seen in this survey are higher than levels reported in previously published surveys in the UK. Reported rates of post splenectomy vaccination against S. pneumoniae in both the UK and North America in 1993 ranged from 10% to 36%. However, there still remains a substantial proportion of splenectomised patients in Lothian, including some of those with the highest risk of infection, who are not vaccinated or prescribed prophylaxis as recommended.

Adolescent↗
PubMed1999

Hepatitis G virus/GBV-C persistence: absence of hypervariable E2 region and genetic analysis of viral quasispecies in serum and lymphocytes.

Persistent infection with hepatitis G virus (HGV) or GB virus-C (GBV-C) is common and may last for years. In addition, the principal site of virus replication remains undefined. Sequencing studies of E2 in four patients showed that a hypervariable region equivalent to that of hepatitis C virus (HCV) was absent and that viral quasispecies were less frequent than in HCV infection, particularly with respect to amino acid variation. Recurrence of viraemia following interferon treatment did not result in the emergence of new quasispecies. Virus persistence therefore does not appear to be related to immune escape by strains bearing a hypervariable E2 region. We also investigated whether virus replication occurred in peripheral blood mononuclear cells. The positive-RNA strand of the virus, but no negative strand, was detected in both serum and lymphocytes. The lymphocytes harbouring the virus were CD4 and CD19 positive. Direct sequencing and cloning of amplicons from the region of the non-structural 3 (NS3) protein showed that the nucleotide sequences in lymphocytes were different from those in serum and did not represent any of the minor serum quasispecies. Although evidence of replication in lymphocytes has not been forthcoming, the differences in sequences between serum and lymphocytes suggest that circulating virus originates from a non-hepatic site, other than lymphocytes.

Adult↗
PubMed1999

Smoking, drinking, and other life style factors and cognitive function in men in the Caerphilly cohort.

STUDY OBJECTIVES: To examine the cognitive function in a large, ongoing cohort study of older men, and to identify associations with social and lifestyle factors. DESIGN: A cross sectional study of cognitive function was conducted within the Caerphilly Prospective Study of Heart Disease and stroke. SETTING: The Caerphilly Study was originally set up in 1979-83 when the men were 45-59 years of age. Extensive data are available on a wide range of lifestyle and other factors of possible relevance to cognitive decline. Associations between some of these and cognitive function are reported. PARTICIPANTS: A representative sample of 1870 men aged 55-69 years. MAIN RESULTS: Age, social class, medication, and mood were found to be powerful determinants of performance. Self report data on the involvement of the men in leisure pursuits were examined by factor analysis. This indicated that the more intellectual leisure pursuits are the most strongly linked with performance. A measure of social contact showed a weak positive association with the test scores. Current cigarette smokers gave lower test cognitive function scores than either men who had never smoked, or ex-smokers. There was however no evidence of any gradient in function with the total lifetime consumption of tobacco. The disparity between these two data sets suggests that there had been prior selection of men who had originally started to smoke, but more particularly selection of those who later quit smoking. There was no significant association between alcohol consumption and cognitive function, though ex-drinkers had markedly lower test scores than either current drinkers or men who had never drunk alcohol. This seemed probably to be a consequence of an high prevalence of illness among the ex-drinkers. CONCLUSIONS: Age and social class show strong associations with cognitive function. Leisure persuits and social contact are also both positively associated. Neither tobacco smoking nor the drinking of alcohol seem to be associated with cognitive function, though there is evidence suggestive of self selection of both men who had never smoked and ex-smokers.

Age Factors↗
PubMed1998

Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors.

Liver fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSC), which proliferate during fibrotic liver injury. We have studied a model of spontaneous recovery from liver fibrosis to determine the biological mechanisms mediating resolution. Livers were harvested from rats at 0, 3, 7, and 28 d of spontaneous recovery from liver fibrosis induced by 4 wk of twice weekly intraperitoneal injections with CCl4. Hydroxyproline analysis and histology of liver sections indicated that the advanced septal fibrosis observed at time 0 (peak fibrosis) was remodeled over 28 d of recovery to levels close to control (untreated liver). alpha-Smooth muscle actin staining of liver sections demonstrated a 12-fold reduction in the number of activated HSC over the same time period with evidence of HSC apoptosis. Ribonuclease protection analysis of liver RNA extracted at each recovery time point demonstrated a rapid decrease in expression of the collagenase inhibitors TIMP-1 and TIMP-2, whereas collagenase mRNA expression remained at levels comparable to peak fibrosis. Collagenase activity in liver homogenates increased through recovery. We suggest that apoptosis of activated HSC may vitally contribute to resolution of fibrosis by acting as a mechanism for removing the cell population responsible for both producing fibrotic neomatrix and protecting this matrix from degradation via their production of TIMPs.

Animals↗
PubMed1998

Natural history and molecular biology of hepatitis G virus/GB virus C.

BACKGROUND: The hepatitis G virus (HGV) or GB virus C (GBV-C) is a new member of the Flaviviridae family. The virus is transmitted by transfusion of blood, infusion of some blood products, and by parenteral exposure to blood during intravenous drug use (IVDU) and haemodialysis. Transmission from mother to infant and by sexual contact has also been documented. Although the virus has been found in patients with acute and chronic hepatitis, evidence of disease association has not been forthcoming. The majority of patients carry the virus in the absence of liver enzyme abnormalities. OBJECTIVES: To review what is currently known about HGV/GBV-C in order to evaluate its similarity with other members of the Flaviviridae and the association of the virus with disease. RESULTS: The genomic organisation of the virus is typical for Flaviviridae, with long 5' and 3' untranslated regions (UTR). However, a clearly identifiable nucleocapsid encoding region is lacking. Polyprotein synthesis is mediated through an internal ribosome entry site (IRES) contained within the 5' UTR. Phylogenetic tree analysis of sequences derived from this region has demonstrated the existence of at least three genotypes. Apart from serum, HGV-RNA has been detected in lymphocytes also, but the quasispecies present in the two compartments appear to be different. The envelope glycoprotein E2 lacks a hypervariable region and is potentially the target of a neutralising antibody response. CONCLUSION: Molecular analysis of HGV reveals close similarity of the virus with HCV. However, an association of the virus with liver disease remains unresolved and no association of the virus with hepatocellular carcinoma has been reported.

Flaviviridae↗
PubMed1998

Homocysteine and ischaemic heart disease in the Caerphilly cohort.

Elevated circulating total homocyst(e)ine concentrations are associated with a higher prevalence of ischaemic heart disease (IHD). We utilized data from the Caerphilly Prospective Cohort Study to assess the predictive power of the serum total homocyst(e)ine concentration for future IHD. Serum total homocyst(e)ine concentrations were measured in 2290 men in the Caerphilly cohort, a representative population sample of men aged 50-64 years. During a 5-year follow-up period, 56 men suffered fatal IHD, 77 had a non-fatal myocardial infarction, while 21 were found to have ECG evidence of myocardial infarction (MI) when examined at follow-up. The mean serum total homocyst(e)ine concentration in the total of 154 men who experienced an incident IHD event was 12.4 micromol/l, whereas the 2136 men who experienced no such event had a mean level of 11.7 micromol/l. The difference between these means, examined by logistic regression and standardising for the effects of differences in age, social class, smoking, BMI, diabetes, HDL-cholesterol and prevalent IHD is 0.47 micromol/l (95% CI = -0.13 to 1.11 micromol/l). The mean difference for the 56 men who died, and whose death was attributed to IHD, is 0.81 micromol/l (95% CI= -0.17 to 1.88 micromol/l) after correction for confounding factors. Vitamin nutritional status and alcohol intake were significant negative determinants of serum total homocyst(e)ine concentrations; the effect of alcohol is explained by the folic acid content of beer, which is the preferred alcoholic beverage in Caerphilly. It is concluded that the serum total homocyst(e)ine concentration is weakly predictive of IHD events, though in the present data adjustments for other factors attenuated the relationship and it became not statistically significant (P > 0.05).

Biomarkers↗
PubMed1998

Reversal of excitatory postsynaptic potential/spike potentiation in the CA1 area of the rat hippocampus.

In the CA1 area of the hippocampus, low frequency and tetanic conditioning stimuli are known to trigger long-term depression and potentiation of synaptic responses respectively and to produce irreversible excitatory postsynaptic potential/spike potentiation, i.e. an increase of the probability of discharge of the neurons. Using simultaneous extracellular recordings in stratum radiatum and stratum pyramidale in the CA1 area of the rat hippocampus, brief application of the K+ channel blocker tetraethylammonium resulted both in long-term potentiation of synaptic responses and in excitatory postsynaptic potential/spike potentiation that could be reversed by subsequent low frequency or tetanic stimuli. Excitatory postsynaptic potential/spike potentiation and its subsequent reversal by an electrical conditioning stimulus were found to have an N-methyl-D-aspartate receptor-independent component. We conclude that the reversal of excitatory postsynaptic potential/spike potentiation can occur and that it does not require the induction of long-term modification of synaptic responses.

2-Amino-5-phosphonovalerate↗
PubMed1998

Hepatitis G virus does not cause significant liver disease after liver transplantation.

The aim of this study was to determine the prevalence of infection with the newly described hepatitis G virus (HGV) in a liver transplant cohort, and to establish the frequency and nature of hepatitis in those with and without HGV infection. A reverse transcriptase-polymerase chain reaction technique was employed to determine viraemia in the patients, and liver biopsies taken at different times after transplantation were assessed histologically. Hepatitis G virus RNA was detected in 47% of the liver transplant recipients investigated. Those positive for HGV had received significantly more blood or blood products than the HGV-negative patients. The frequency of abnormal liver function tests was similar in HGV-positive and HGV-negative recipients. Bile duct epithelial cell damage was more frequently seen in those with HGV viraemia. This study indicates that almost half of the liver transplant recipients in Northern England are positive for HGV, and that infection is associated with exposure to blood and blood products. It appears that, in the immunosuppressed patient, HGV does not cause clinically significant liver disease, at least up to 2 years after transplantation. If HGV infection is associated with hepatitis outside this clinical setting, it is likely that the liver damage is immunopathologically mediated rather than as a result of direct viral cytotoxicity.

Alanine Transaminase↗
PubMed1997

Trichomoniasis in a postmenopausal woman cured after discontinuation of estrogen replacement therapy.

BACKGROUND: Epidemiologic and experimental data suggest that estrogen has a salutary effect on Trichomonas vaginalis. CASE: A metronidazole-allergic postmenopausal woman was cured of vaginal trichomoniasis in association with discontinuation of estrogen replacement therapy. CONCLUSION: Hormonal manipulation should be studied for the management of women with trichomoniasis who are allergic to metronidazole or who are infected with metronidazole-resistant strains of Trichomonas vaginalis.

Antitrichomonal Agents↗
PubMed1997

Identification, prevalence and aspects of molecular biology of hepatitis G virus.

Hepatitis G virus (HGV) is a newly identified member of the Flaviviridae family. The positive-sense RNA genome of the virus contains a single open reading frame that encodes the viral polyprotein. Its genomic organization is similar to that of the hepatitis C virus (HCV) with which it has only 25% homology at the nucleotide level. Nucleotide sequences from the NS-3 helicase region of HCV varied by 10-30%. HGV is therefore much less variable than HCV. Construction of phylogenetic trees, and calculation of mean distances between possible subtypes, indicated one level of variation in NS-3 sequences: the degree of variation between isolates was similar to that observed between HCV subtypes. Thus no evidence for clustering of sequences into multiple genotypes was found. The virus is transmissible through blood transfusion and by exposure to blood products or intravenous drug use, and may result in acute or chronic hepatitis. A causative role of HGV in acute and chronic hepatitis is not yet established. Concurrent infection with hepatitis B virus (HBV) and HCV is common and persistent viraemia has been documented for many years, in many cases, in the absence of transaminase elevations.

Antiviral Agents↗
PubMed1996

Whole genome analysis of hepatitis B virus from four cases of fulminant hepatitis: genetic variability and its potential role in disease pathogenicity.

The precore stop-codon variant of hepatitis B virus (HBV) has been associated with fulminant hepatitis but is also found in patients with persistent infection and chronic hepatitis. We have examined the possibility that the severe outcome of infection in patients with fulminant disease may be a result of additional genomic variation. We sequenced the entire HBV genome from three patients of Greek and one patient of Chinese origin with fulminant hepatitis, and from two patients with hepatitis B e antigen (HBeAg) positive chronic infection from the same regions, using direct sequencing of amplified viral DNA. Three of the fulminant cases were infected with the precore stop-codon variant HBeAg negative) and the fourth with the wild-type (HBeAg) positive virus. We compared sequences from our four fulminant isolates, and an additional fulminant isolate reported by others, with HBeAg positive carriers from the same regions and 12 published HBV genomes. There was a higher number of nucleotide and amino-acid substitutions throughout the HBV genome in the precore variant fulminant sequences than in the wild type. A cluster of mutations previously identified in the X region (126-132) in sequences reported in Japanese patients and encompassing the Enhancer II-Core Promoter region (1751-1768), were not found in our patients. We conclude that although there are no changes common to all sequences of HBV isolates from fulminant cases, some of these changes are in recognized cis-acting regulatory elements, whilst others are in the immediate vicinity of such elements. The effect of these mutations on viral genome transcription must now be determined.

Amino Acid Sequence↗
PubMed1996

Dietary magnesium does not predict ischaemic heart disease in the Caerphilly cohort.

OBJECTIVES: To examine the association between dietary magnesium intake and the risk of an ischaemic heart disease (IHD) event. DESIGN: Estimates were made of dietary magnesium intake from food frequency records, supplemented by seven-day weighted intake records. The subsequent incidence of ischaemic heart disease events was recorded. The relative odds of an IHD event was related to base-line magnesium intake. SETTING: Data on dietary magnesium intakes are available for 2172 men aged 45-59 y in the Caerphilly cohort. These have now been followed for ten years since base-line dietary data were collected, and during this time a total of 269 IHD events occurred. Of these, 96 were acute deaths (ICD 410) and 136 were non-fatal myocardial infarctions. RESULTS: The overall mean dietary intake of magnesium was estimated to be 279 (s.d. 83) mg/day. The daily intake of those men who later experienced any IHD event was 266 (s.d. 84) mg/day and this differs from that in men who experienced no IHD event during this time (281 mg, P < 0.05). Men who suffered an acute IHD death had even lower intakes (mean 253 (s.d. 79); P < 0.005). Age, smoking habit, energy intake and alcohol consumption are all significantly associated with both Mg intake and IHD risk and are therefore possible confounding factors. Standardisation for these factors reduces the difference for all IHD events to 2.9 (s.e.m. 3.6) mg Mg/day, P > 0.05, and to 0.9 (s.e.m. 5.8) mg for acute IHD death. Similarly, when the men are ranked into fifths by their daily Mg intake, 70 of the 434 men with the lowest intakes went on to experience an IHD event, compared with only 41 of the 434 men with the highest Mg intakes. The relative odds (RO) for the fifth of men with the lowest intakes, compared with the fifth with the highest intakes, is 1.86 (P < 0.005), but standardisation for the confounding factors leads again to a loss of significance (RO 1.52, P > 0.05). CONCLUSION: Although trends in the data are suggestive, data from the Caerphilly cohort give no certain evidence that dietary magnesium intake is independently predictive of ischaemic heart disease in the population studied.

Alcohol Drinking↗
PubMed1995

Training general practitioners in surgical and obstetrical emergencies in Ethiopia.

A 6-month course for training general practitioners (GPs) in surgical emergencies was developed and piloted in Ethiopia. The course was designed after an assessment of the surgical manpower needs in Ethiopia. Seven GPs were selected by the Ministry of Health (MOH) from rural hospitals that had no surgical specialists but had operating facilities. The course consisted of 1 week of lectures followed by 11 weeks each in obstetrics/gynaecology and general surgery. The GPs trained in district hospitals under the supervision of surgical specialists. Emphasis was placed on practical experience in managing a limited number of previously identified surgical emergencies. Follow up 9 months after completion of the course showed that five of the seven GPs had completed significant numbers of life saving procedures. Complications occurred largely in advanced disease. Difficulties remain with the recognition of the GPs' training and their supervision. We conclude that GPs can be trained to provide life saving surgery in a short training programme at a modest cost, but mechanisms for ensuring ongoing support need to be established.

Emergency Medical Services↗
PubMed1994

High school students' knowledge, attitude and practice of contraception in Harer town, eastern Ethiopia.

A survey of knowledge, attitude and practice of contraception was carried out among 1,674 students (mean age 17.4 years) in Harer town, eastern Ethiopia. Fifty-four per cent of the students spontaneously mentioned a modern contraceptive method when asked, but large numbers of students did not know the answers to specific questions about prevention of pregnancy. The students were receptive to more information in schools on sexuality and contraception. Overall, 20% of females and 65% of males admitted to having had sexual intercourse at least once. Among sexually active females, 60% said they were using a contraceptive method. However, 76% of these were using only the calendar method. Twenty per cent of the sexually experienced female students had been pregnant, and of these 56% had elected for induced abortions. If only unmarried students are considered, 75% of those who had been pregnant had had an induced abortion. Since induced abortions are not legal in Ethiopia, these students are at high risk for complications of abortions.

Abortion, Illegal↗