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Biomedical subjects

J Fryer

Publications and source records attributed to J Fryer.

At least 19 recordsLinked to original sources

The association between non-melanoma skin cancer and osteoporotic fractures--a population-based record linkage study.

UNLABELLED: We studied the association between osteoporotic fractures and prior non-melanoma skin cancer (NMSC, a biomarker for cumulative sun exposure). The risk of prior NMSC in our fracture cohort was significantly reduced (standardised incidence ratio 0.69, 95% CI 0.61, 0.78). Adequate lifetime sun exposure may be necessary to protect against osteoporotic fractures in later life. INTRODUCTION: The relationship between cumulative sun exposure and osteoporotic fractures is uncertain. We aimed to study the association between non-melanoma skin cancer (NMSC), a marker of cumulative sun exposure, and osteoporotic fractures in an older cohort. METHODS: A retrospective cohort study in southern Tasmania in people aged at least 50 years with incident radiographic fracture (n = 2,283) was carried out. By record linkage to the Tasmanian Cancer Registry the cohort was followed backwards through time until the occurrence of NMSC or end-of follow-up. Relative risk was estimated by the standardised incidence ratio (SIR) using sex-, age- and calendar year-specific cancer incidence rates in southern Tasmania as reference. RESULTS: The incidence of prior NMSC in the fracture cohort was 31% lower than for the general population (SIR 0.69, 95% CI 0.61, 0.78). This effect was significant for most fracture subtypes except pelvic and wrist fractures and observed for both NMSC subtypes, squamous cell carcinoma and basal cell carcinoma. CONCLUSIONS: Older people with osteoporotic fractures may have had lifestyles linked to lower cumulative sunlight exposure. Achieving a balance between adequate lifetime sun exposure and protection against its adverse effects (such as fractures and skin cancer) may require assessment of individual risks.

Age Distribution↗

Laparoscopic-assisted right lobe donor hepatectomy.

The major impediment to a wider application of living donor hepatectomy, particularly of the right lobe, is its associated morbidity. The recent interest in a minimally invasive approach to liver surgery has raised the possibility of applying these techniques to living donor right lobectomy. Herein, we report the first case of a laparoscopic, hand-assisted living donor right hepatic lobectomy. We describe the technical aspects of the procedure, and discuss the rationale for considering this option. We propose that the procedure, as described, did not increase the operative risks of the procedure; instead, it decreased potential morbidity. We caution that this procedure should only be considered for select donors, and that only surgical teams familiar with both living donor hepatectomy and laparoscopic liver surgery should entertain this possibility.

Adult↗

Calcium supplementation for improving bone mineral density in children.

BACKGROUND: Clinical trials have shown that calcium supplementation in children can increase bone mineral density (BMD) although this effect may not be maintained. There has been no quantitative systematic review of this intervention. OBJECTIVES: . To determine the effectiveness of calcium supplementation for improving BMD in children. . To determine if any effect varies by sex, pubertal stage, ethnicity or level of physical activity, and if any effect persists after supplementation is ceased. SEARCH STRATEGY: We searched CENTRAL, (Cochrane Central Register of Controlled Trials) (Issue 3, 2005), MEDLINE (1966 to 1 April 2005), EMBASE (1980 to 1 April 2005), CINAHL (1982 to 1 April 2005), AMED (1985 to 1 April 2005), MANTIS (1880 to 1 April 2005) ISI Web of Science (1945 to 1 April 2005), Food Science and Technology Abstracts (1969 to 1 April 2005) and Human Nutrition (1982 to 1 April 2005). Conference abstract books (Osteoporosis International, Journal of Bone and Mineral Research) were hand-searched. SELECTION CRITERIA: Randomised controlled trials of calcium supplementation (including by food sources) compared with placebo, with a treatment period of at least 3 months in children without co-existent medical conditions affecting bone metabolism. Outcomes had to include areal or volumetric BMD, bone mineral content (BMC), or in the case of studies using quantitative ultrasound, broadband ultrasound attenuation and ultrasonic speed of sound, measured after at least 6 months of follow-up. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data including adverse events. We contacted study authors for additional information. MAIN RESULTS: The 19 trials included 2859 participants, of which 1367 were randomised to supplementation and 1426 to placebo. There was no heterogeneity in the results of the main effects analyses to suggest that the studies were not comparable. There was no effect of calcium supplementation on femoral neck or lumbar spine BMD. There was a small effect on total body BMC (standardised mean difference (SMD) +0.14, 95% CI+0.01, +0.27) and upper limb BMD (SMD +0.14, 95%CI +0.04, +0.24). Only the effect in the upper limb persisted after supplementation ceased (SMD+0.14, 95%CI+0.01, +0.28). This effect is approximately equivalent to a 1.7% greater increase in supplemented groups, which at best would reduce absolute fracture risk in children by 0.1-0.2%per annum. There was no evidence of effect modification by baseline calcium intake, sex, ethnicity, physical activity or pubertal stage. Adverse events were reported infrequently and were minor. AUTHORS' CONCLUSIONS: While there is a small effect of calcium supplementation in the upper limb, the increase in BMD which results is unlikely to result in a clinically significant decrease in fracture risk. The results do not support the use of calcium supplementation in healthy children as a public health intervention. These results cannot be extrapolated to children with medical conditions affecting bone metabolism.

Adolescent↗

Cavitary Legionella pneumonia in a liver transplant recipient.

This report describes the clinical course of a liver transplant recipient in whom cavitary pneumonia developed due to Legionella pneumophila. We review the experience with cavitary pulmonary processes caused by Legionella species in liver allograft recipients and describe the diagnostic microbiology of this organism. The clinical course of this patient demonstrates the importance of considering legionellosis in the differential diagnosis of lung abscesses after liver transplantation and the diagnostic difficulties encountered with this bacterium.

Adult↗

Spontaneous bilateral internal jugular vein thrombosis: a sign of metastasis.

Head and neck swellings are common referrals to the otolaryngology department, with a wide range of aetiologies. Internal jugular vein thrombosis presenting as swelling in the neck is a rare occurrence. The authors report a case of bilateral internal jugular vein thrombosis secondary to malignant lymphadenopathy of unknown origin. The patient presented with a short history of a diffuse swelling in the neck with neck stiffness. Examination revealed palpable cervical and axillary lymphadenopathy. Causes of spontaneous internal jugular vein thrombosis were discussed.

Adult↗

Fatal brain stem event complicating acute pancreatitis.

Acute pancreatitis, developing in a patient with chronic renal failure, was complicated by a fatal neurological illness during which MRI showed pontine and extrapontine changes consistent with pontine and extrapontine myelinolysis. At post mortem, acute pancreatitis was confirmed but the neuropathological findings were more in keeping with an unusual presentation of acute haemorrhagic leucoencephalitis, perhaps even representing a form of 'pancreatic encephalopathy'. Although the development of CT and MRI scanning has greatly increased the resolution of neuroimaging and facilitated diagnosis during life, the value of autopsy examination is confirmed in cases such as this. Sometimes the findings may raise more questions than may have been answered - this too is an important function!

Acute Disease↗

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Alzheimer Disease↗

Single vs. dual vessel porcine extracorporeal liver perfusion.

BACKGROUND: The use of porcine extracorporeal liver perfusion (PECLP) to provide temporary hepatic support for patients in fulminant hepatic failure has been limited by the fact that individual perfusions can be sustained for only a few hours. Inadequate liver function and/or hemodynamic instability are the major contributing factors for early interruption of PECLP. Recent reports suggest that the choice of single (portal vein only) vs dual (portal vein and hepatic artery) vessel perfusion may influence the duration of perfusion. We hypothesize that PECLP with single vessel perfusion (SVP) is associated with worse liver function and greater hemodynamic instability than PECLP with dual vessel perfusion (DVP). MATERIALS AND METHODS: To eliminate the potentially confounding influences of liver failure and xenograft rejection, liver isografts procured from White-Landrace pig donors were perfused by either SVP or DVP via an extracorporeal circuit established with normal White-Landrace pig recipients. The function of perfused livers was evaluated by measuring production of bile and Factors V and VIII, clearance of ammonia and lactate, and extraction of O(2) at baseline and at 0, 1, 3, 6, 12, and 24 h after initiation of PECLP. The impact of PECLP on recipient hemodynamic status was assessed by monitoring BP, heart rate, urine output, O(2) saturation, etc. Among other parameters evaluated were serum albumin and total protein and hepatic release of IL-1beta and nitric oxide to assess their possible contributions to hemodynamic instability. RESULTS: DVP and SVP livers cleared ammonia and lactate similarly. Both approaches were associated with progressive hypoalbuminemia and hypoproteinemia. DVP livers produced more bile and Factor V and were associated with less recipient hypotension and IL-1beta and NO release than SVP livers. CONCLUSIONS: Livers with DVP function better than livers with SVP. The duration of PECLP can be limited by recipient hypotension, although this complication is less severe with DVP than with SVP.

Ammonia↗

Body mass index as a predictor of hepatic steatosis in living liver donors.

Evaluation of the living donor for liver transplantation is a complex process involving such invasive studies as liver biopsy and angiography. It is important to establish the likelihood and extent of hepatic steatosis in living donors by clinical, imaging, and biochemical parameters to avoid performing a liver biopsy, if possible. In this study, the predictive value of body mass index (BMI), liver chemistry tests, and imaging studies was compared with liver histological examination in 33 potential living donors. Patients were grouped and compared based on their BMI (<25, 25 to 28, >28). No patient with a BMI less than 25 had hepatic steatosis. Of patients with a BMI of 25 to 28, steatosis was found on biopsy in 3 of 9 patients. Thirteen of 17 patients (76%) with a BMI greater than 28 had hepatic steatosis on liver biopsy. There was a significant correlation between BMI and overall grade of steatosis (R = 0.49). All subjects with steatosis detected on magnetic resonance imaging (MRI) or computed tomography (CT) had steatosis on biopsy, and all but 2 such patients had greater than 10% steatosis on biopsy. Conversely, 30% of patients in the MRI group and 24% of patients in the CT group failed to show hepatic steatosis when it was present on biopsy. Thus, it appears that liver biopsy could be avoided in subjects with a normal BMI and absence of risk factors. Individuals with a high BMI should undergo liver biopsy because biochemical and imaging data are currently inadequate to determine the extent of steatosis. Future studies should aim at improving the sensitivity of imaging techniques in the diagnosis of steatosis.

Adolescent↗

Prescribers prefer people: The sources of information used by doctors for prescribing suggest that the medium is more important than the message.

AIMS: The sources of prescribing information are legion but there is little knowledge about which are actually used in practice by doctors when prescribing. The aims of this study were to determine the sources of prescribing information considered important by doctors, establish which were used in practice, and investigate if hospital and primary care physicians differed in their use of the sources. METHODS: Two hundred general practitioners (GPs) and 230 hospital doctors were asked to rate information sources in terms of their importance for prescribing 'old' and 'new' drugs, and then to name the source from which information about the last new drug prescribed was actually derived. RESULTS: Among 108 GPs, the Drugs and Therapeutics Bulletin and medical journal articles were most frequently rated as important for information on both old and new drugs while pharmaceutical representatives and hospital/consultant recommendations were more important for information on new drugs, as opposed to old. In practice, information on the last new drug prescribed was derived from pharmaceutical representatives in 42% of cases and hospital/consultant recommendations in 36%, with other sources used infrequently. Among 118 hospital doctors, the British National Formulary (BNF) and senior colleagues were of greatest theoretical importance. In practice, information on the last new drug prescribed was derived from a broad range of sources: colleagues, 29%; pharmaceutical representatives, 18%; hospital clinical meetings, 15%; journal articles, 13%; lectures, 10%. GPs and hospital doctors differed significantly in their use of pharmaceutical representatives (42% vs 18%) and colleagues (7% vs 29%) as sources of prescribing information (P < 0.0001 for both). CONCLUSIONS: The sources most frequently rated important in theory were not those most used in practice, especially among GPs. Both groups under-estimated the importance of pharmaceutical representatives. Most importantly, the sources of greatest practical importance were those involving the transfer of information through the medium of personal contact.

Communications Media↗

Inducible, heterologous expression of human alpha7-nicotinic acetylcholine receptors in a native nicotinic receptor-null human clonal line.

Tetracycline-regulated expression of recombinant nicotinic acetylcholine receptors (nAChR) composed of human alpha7 subunits is achieved in native nAChR-null SH-EP1 human epithelial cells. alpha7 subunits are heterologously expressed as messenger RNA and as components of 125I-labeled alpha-bungarotoxin (I-Bgt)-binding nAChR ( approximately 10 pmol per milligram of membrane protein) at levels sensitive to the amount of tetracycline in cell growth medium. I-Bgt-binding alpha7-nAChR appear on the cell surface pool and in intracellular pools. The pharmacological profile for drug competition toward I-Bgt binding to these recombinant alpha7-nAChR matches that of human native alpha7-nAChR naturally expressed in SH-SY5Y human neuroblastoma cells (rank order potency methyllycaconitine>1, 1-dimethyl-4-phenylpiperazinium>(-)nicotine>cytisine>carbamylch oli ne> /=d-tubocurarine). Chronic exposure to nicotine induces up-regulation of human recombinant alpha7-nAChR (80% up-regulation at 10 microM nicotine) just as it does native alpha7-nAChR in other human cell lines. These studies confirm expression of nAChR as homooligomers of human alpha7 subunits from transgenes, establish a native nAChR-null background for such expression, and demonstrate that this expression can be regulated to facilitate studies of human alpha7-nAChR.

Acetylcholine↗

Repetition of deliberate self-poisoning in an Australian hospital-treated population.

OBJECTIVES: To describe the hospital-treated prevalences for repeat deliberate self-poisoning (RDSP) and the demographic characteristics of the RDSP group, and to compare the RDSP and non-RDSP groups. DESIGN: Prospective longitudinal cohort study, with a one- to four-year follow-up. SETTING: The Hunter Area Toxicology Service (HATS), a regional toxicology treatment centre in New South Wales. SUBJECTS: 1238 consecutive DSP patients referred to hospital, 1992-1994, with follow-up through 1995. OUTCOME MEASURES: Deliberate self-poisoning (DSP) admissions within one year (RDSP-1), within six months (RDSP-6m), and within 28 days (RDSP-28d) of any other DSP admission by the same patient; length of stay; demographic characteristics; and drugs ingested. RESULTS: 175 patients (14.1%) repeated DSP during the study; 165 (13.3%) were classified as RDSP-1, giving a patient prevalence of hospitalisation in the range of 14.6 to 20.7 per 100,000 per year. Fifty-six RDSP-28d patients (33.9% of RDSP-1) accounted for 49.8% of the RDSP-1 admissions, and 123 RDSP-6m patients (74.5% of RDSP-1) accounted for 83.5% of RDSP-1 admissions. For RDSP-1, the male:female ratio was 1:1.9, with 35.7% unemployed, 29.1% pensioners and 15.8% married or in de facto relationships. RDSP-1 patients had a shorter length of stay (3 h), which was not clinically important. RDSP was more likely for the 25-34 years age group (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.17-4.29) and the 35-44 years age group (OR, 2.12; 95% CI, 1.02-4.39) than the 10-18 years group, and more likely for women than men (OR, 1.69; 95% CI, 1.17-2.46). Being married/de facto reduced the risk for repetition (OR, 0.55; 95% CI, 0.31-0.96) compared with being single. Medications indicated for psychiatric illness were most commonly used for DSP. CONCLUSIONS: Many patients who repeat DSP do so after a very brief interval and account for a disproportionate number of hospitalisations. Availability of psychiatric medications for DSP patients is a possible area of intervention.

Adolescent↗

Low bioavailability of cyclosporine microemulsion and tacrolimus in a small bowel transplant recipient: possible relationship to intestinal P-glycoprotein activity.

With intestine transplants the allograft is dependent on itself for maintenance of adequate immunosuppression. We evaluated an intestinal transplant recipient who required very large doses of either tacrolimus or cyclosporine emulsion to achieve acceptable blood concentrations. Pharmacokinetic studies revealed bioavailabilities of 2% and 6% respectively, while D-xylose and B12 absorption were found to be within normal limits and fecal fat was only slightly increased, suggesting that there was a selective absorptive defect for these drugs. Biopsies of the allograft ileum revealed a high P-glycoprotein activity compared to the jejunum or to intestinal biopsies from other normal subjects. This may be a contributing factor to poor immunosuppressive drug absorption in this patient and others.

Biological Availability↗

Comparison of family history measures used to identify high risk of coronary heart disease.

We examined 15 published continuous family history measures (scores) as well as two new formulations in terms of several desirable properties. We applied the scores to sample pedigrees and found that some systematically increase with family size. In contrast to aggregate scores, non-aggregate scores are sensitive to the age, sex, and covariate status of individual relatives but are unstable when the families are small. We also applied these scores to our own population case-control data, characterised by a high proportion of missing and false-negative responses. In these small families, all scores provided significant discrimination between CHD cases and controls beyond the usual categorical definition of positive family history, but appeared no better than detailed categorical definitions or even simple counts. Our new formulations offer no solution to the problems of few data; most scores apply asymptotic approximations to differences between observed and expected number of affected relatives and are not suited to small families. All scores would be improved by ruling out families with only one affected relative, as is being done in the NHLBI Family Heart Study. We recommend that researchers, when using a family history measure, consider the number of informative families and other characteristics of their data prior to choosing any particular formulation.

Age Factors↗

IgY antiporcine endothelial cell antibodies effectively block human antiporcine xenoantibody binding.

Avian IgY antibodies are structurally different from mammalian IgGs and do not fix mammalian complement components or bind human Fc receptors. As these antibody-mediated interactions are believed to play significant roles in both hyperacute rejection (HAR) and acute vascular xenograft rejection (AVXR), IgY antibodies to xenoantigen target epitopes may inhibit these rejection processes. In this report, we show that chicken IgY antibodies to alpha-Gal antigen epitopes and to other porcine aortic endothelial cell (PAEC) antigens block human xenoreactive natural antibody binding to both porcine and rat cardiac tissues and porcine kidney tissues. Chicken IgY antibodies blocked complement-mediated lysis of PAECs by human serum, and inhibited antibody-dependent cell-mediated lysis of PAECs by heat-inactivated human serum plus peripheral blood leukocytes. Binding of IgY to porcine endothelial cells did not affect cell morphology nor expression of E-selectin. These results suggest that avian IgYs could be of potential use in inhibiting pig-to-human xenograft rejection.

Animals↗

Correction for biases in a population-based study of family history and coronary heart disease. The Newcastle Family History Study I.

In this paper, the authors report on the design of a population-based case-control study of family history as a risk factor for coronary heart disease (CHD). They studied the characteristics of subjects who completed a detailed family history questionnaire in 1992-1994 as well as the accuracy of recall of family history in order to quantify both selection and recall biases. Coronary disease cases were enrolled through the Newcastle MONICA Project (Monitoring Trends and Determinants in Cardiovascular Disease), which registered all suspected heart attacks and sudden cardiac deaths in the Lower Hunter region of New South Wales, Australia, between August 1984 and March 1994. Controls were selected at random from the New South Wales electoral roll. The response rate was 76% in cases and 62% in controls; the major factor associated with participation in the study was perceived family history of CHD, more so in the control series than in the case series. Accuracy was determined by comparing information obtained from the proband with that recorded on death certificates. In first-degree relatives, sensitivity of CHD recall was 85% (95% confidence interval (CI) 74-92%) in cases and 95% (95% CI 84-99%) in controls, while specificity was 59% (95% CI 49-69%) and 74% (95% CI 65-82%), respectively. The net bias in both selection and recall is toward the null and hence the comparisons provide a conservative estimate of risk of CHD associated with a positive family history.

Aged↗

Risk associated with various definitions of family history of coronary heart disease. The Newcastle Family History Study II.

The authors carried out a population-based case-control study to estimate the risk of an acute coronary disease event associated with various definitions of a family history of coronary heart disease (CHD). A detailed family history questionnaire was completed by 403 cases and 236 controls in Newcastle, New South Wales, Australia from 1992 to 1994. Odds ratios of an acute coronary disease event adjusted for proband age and sex ranged from 2.7 (95% confidence interval (CI) 1.8-4.1) for the simplest definition (one or more first-degree relatives with CHD at any age) to 5.4 (95% CI 1.7-16.8) for the most stringent definition (two or more first-degree relatives with CHD before age 55 years). In a series of nested models, the authors examined the improvement in model fit as each component of the detailed family history was added. Additional information was provided by accounting for "don't know" responses, the number of affected relatives, the age of the affected relative, and whether the first-degree relative was a sibling rather than a parent. The results were similar when the data were analyzed as a cohort design with proband disease status as the exposure variable. The authors suggest that, to facilitate preventive efforts in a population, more detailed family history definitions should be used to better target high risk subjects.

Age of Onset↗

Absorptive function following small intestinal transplantation.

All studies involving small intestinal transplantation and absorptive function are reviewed. The effects ischemia-reperfusion, lymphatic disruption, denervation, rejection, immunosuppressive medication, and infection are elucidated as far as the studies allow. Species differences are discussed. Conclusions regarding the major absorptive defects are drawn.

Denervation↗