Kidney failure in liver transplantation: it is time for action.
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Humans↗
Biomedical subjects
C L Davis
Publications and source records attributed to C L Davis.
Investigation of the microstructure and mesotexture formed during thermomechanical controlled rolling in microalloyed steels.
Thermomechanical controlled rolling (TMCR) has been widely used as an effective method to improve the properties of steels. In the present paper, two commercial TMCR microalloyed steels were investigated. The grain size distributions and grain boundary misorientation angles were measured using electron backscattered diffraction patterns obtained using orientation imaging microscopy (OIM). The equivalent grain diameters were also measured using optical microscopy. Mixed coarse- and fine-grained regions were observed and the microhardness values were measured for both areas. Grain boundary misorientation angle distributions showed that the magnitude of mesotexture developed in the steel is dependent upon the rolling passes, the reduction ratio and the rolling temperatures including the finish rolling temperature. The surface layer, up to 2 mm depth, in Com-A steel had about 55% of grain boundaries with a misorientation angle below 12 degrees, much higher than in the central area ( approximately 30%), whereas Com-B steel showed similar distributions from the rolling surface to the centre. Misorientation results obtained from laboratory rolled steel plates with various TMCR procedures are also discussed as are OIM results from Charpy impact brittle fracture surfaces examining the effect of misorientation on crack propagation.
Alloys↗
Differences in understanding of specialist palliative care amongst service providers and commissioners in South London.
This paper describes a study that sought to identify service providers' and commissioners' understanding of specialist palliative care within the context of changing service provision in one area of South London. Using a formative evaluation framework, we examined the views of 44 providers and commissioners from statutory and voluntary health and social care services about their understanding of specialist palliative care services and, in particular, the remit of current service provision delivered by a Marie Curie Centre. Face-to-face audiotaped semi-structured interviews were conducted. A qualitative thematic analysis highlighted a number of issues including a lack of consensus about definitions of palliative care, ambivalence about referral procedures, and a lack of role clarity between specialist and generalist palliative care providers. The study took place within the real world context of changing services and economic pressures. This raises methodological issues about how services are evaluated and what terminology is used to describe end-of-life care. The study findings confirm that confusion about terminology and referral criteria remain major issues for clinical workers and organizations seeking to access services.
Attitude of Health Personnel↗
Quantitation of BK virus load in serum for the diagnosis of BK virus-associated nephropathy in renal transplant recipients.
BK virus-associated nephropathy is an increasingly recognized cause of graft dysfunction among kidney transplant recipients, and definitive diagnosis requires renal biopsy. By using a newly developed, quantitative, real-time polymerase chain reaction (PCR) assay for BK virus DNA, a retrospective analysis was done of sequential serum samples (n=28) from 4 transplant recipients with histopathologically documented BK virus nephropathy and from samples (n=76) from 16 transplant recipient control patients. BK virus DNA was detected in serum samples from all 4 case patients versus 0 of 16 control patients (P< .0001, Fisher's exact test) at a median of 32 weeks (range, 17-61 weeks) before the diagnosis of BK virus nephropathy. BK virus load decreased in 3 of 3 patients after the reduction of immunosuppression and/or nephrectomy. It is concluded that quantitative PCR for BK virus DNA in serum is useful both for identifying transplant recipients at risk for BK virus nephropathy and for monitoring the response to therapy.
Adult↗
Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls.
BACKGROUND: GABA receptor-modifying neurosteroids may play a role in premenstrual syndrome (PMS). The peripheral benzodiazepine receptor (PBR) both regulates the formation of neurosteroids and is, in animals, regulated by ovarian steroids. Alterations in PBR density have been observed in association with several psychiatric disorders. METHODS: We examined the effects of gonadal steroids on lymphocytic PBR density in nine women with prospectively confirmed PMS and nine controls. PBR densities were measured during three pharmacologically controlled conditions: gonadotropin releasing hormone agonist (Lupron)-induced hypogonadism, Lupron plus estradiol, and Lupron plus progesterone replacement. Blood samples were obtained after six weeks of Lupron alone and after 3-4 weeks of estradiol and progesterone replacement. RESULTS: No significant hormone state-related changes in PBR density were observed (ANOVA-R: phase-F(2,32)=1.5, P=0.2). Despite mood symptom development in the subjects with PMS, PBR density did not differ in women with PMS compared to controls across hormonal states (ANOVA-R: F(1,16)=0.6, P=0.4). CONCLUSIONS: PBR densities are not altered in women with PMS and are not changed significantly by selective gonadal steroid administration. Changes in PBR density would not appear to underlie the differential sensitivity to the mood destabilizing effects of ovarian steroids in PMS.
Affect↗
Pre-transplant cardiac testing for kidney-pancreas transplant candidates and association with cardiac outcomes.
BACKGROUND: Coronary artery disease is a major cause of mortality following renal transplantation, especially in those patients with diabetes. The accurate prediction of cardiac risk is therefore a major focus of the pre-transplant evaluation. The objective of this study was to retrospectively evaluate the ability of non-invasive cardiac testing (standard echocardiography, stress echocardiography, exercise tolerance testing, and nuclear myocardial perfusion) performed within 1 yr of kidney-pancreas transplant to predict post-transplant myocardial infarction. METHODS: Clinical history and pre-transplant cardiac testing performed within 1 yr prior to transplantation were reviewed in a non-blinded fashion for 165 kidney-pancreas transplantation patients receiving allografts between June 1990 and May 1998. The predictive values of clinical symptoms and cardiac testing for cardiac events (fatal and non-fatal myocardial infarctions) up to 1 yr post-transplant were calculated. RESULTS: Clinical history had a negative predictive value of 98% for cardiac events occurring within 1 yr following testing and 97% within 1 yr post-transplant. Collectively, non-invasive testing had a negative predictive value of 97% for 1 yr post-testing and 1 yr post-transplant. CONCLUSION: Clinical history alone is highly suggestive but not sufficient for the prediction of post-kidney-pancreas transplant myocardial infarction. Although a useful supplement, cardiac testing does not predict all cardiac events out to 1 yr post-testing. In this high-risk patient population with diabetes and renal failure, other methods of risk assessment are needed to more accurately predict long-term cardiac outcome for patients awaiting transplantation.
Coronary Angiography↗
Interferon and cytotoxic chemotherapy for the treatment of post-transplant lymphoproliferative disorder.
Interferon-alpha and cytotoxic chemotherapy may be effective treatment modalities for the post-transplant lymphoproliferative disorder. Interferon-alpha may result in a complete response in up to 40% of patients, while chemotherapy may be effective in 75% of those failing local surgical excision, a reduction in immunosuppression, and an antiviral agent. Interferon may be used early after diagnosis in patients with relatively slowly growing tumors. Chemotherapy should be selected for patients with bulky, rapidly growing malignancies. The toxicity of chemotherapy may be minimized by discontinuing maintenance immunosuppression during chemotherapy, administering GCSF, and providing antimicrobial prophylaxis. Rejection is minimized by the reintroduction of maintenance immunosuppression when the patient is no longer neutropenic.
Antineoplastic Combined Chemotherapy Protocols↗
Risk factors and mortality associated with calciphylaxis in end-stage renal disease.
BACKGROUND: We conducted a case control study to determine risk factors and mortality associated with calciphylaxis in end-stage renal disease. METHODS: Cases of calciphylaxis diagnosed between December 1989 and January 2000 were identified. Three controls were identified for each hemodialysis patient, with calciphylaxis matched to the date of initiation of hemodialysis. Laboratory data and medication doses were recorded during the 12 months prior to the date of diagnosis and at the time of diagnosis of calciphylaxis. Conditional logistic regression was used to identify risk factors for calciphylaxis. Cox proportional hazards models were used to estimate the risk of death associated with calciphylaxis. RESULTS: Nineteen cases and 54 controls were identified. Eighteen patients were hemodialysis patients, and one had a functioning renal allograft. Diagnosis was confirmed by skin biopsy in 16 cases. Women were at a sixfold higher risk of developing calciphylaxis (OR = 6.04, 95% CI 1.62 to 22.6, P = 0.007). There was a 21% lower risk of calciphylaxis associated with each 0.1 g/dL increase in the mean serum albumin during the year prior to diagnosis and at the time of diagnosis of calciphylaxis (OR = 0.79, 95% CI, 0.64 to 0.99, P = 0.037, and OR = 0.80, 95% CI, 0.67 to 0.96, P = 0.019, respectively). There was a 3.51-fold increase in the risk of calciphylaxis associated with each mg/dL increase in the mean serum phosphate during the year prior to diagnosis (95% CI, 0.99 to 12.5, P = 0.052). At the time of diagnosis of calciphylaxis, for each 10 IU/L increment in alkaline phosphatase, the risk of calciphylaxis increased by 19% (OR = 1.19, 95% CI, 1.00 to 1.40, P = 0.045). Body mass index, diabetes, blood pressure, aluminum, and higher dosage of erythropoietin and iron dextran were not independent predictors of calciphylaxis. Calciphylaxis independently increased the risk of death by eightfold (OR = 8.58, 95% CI, 3.26 to 22.6, P < 0.001). CONCLUSIONS: Female gender, hyperphosphatemia, high alkaline phosphatase, and low serum albumin are risk factors for calciphylaxis. Calciphylaxis is associated with a very high mortality.
Alkaline Phosphatase↗
Osteopontin expression in human cyclosporine toxicity.
BACKGROUND: Osteopontin is a secreted phosphoprotein that has a number of diverse biological functions, including cell signaling, mediation of cell adhesion, migration, and chemoattraction of monocytes/macrophages. Up-regulation of osteopontin expression by proximal tubular epithelium has been demonstrated in both human and rodent models of renal injury in association with macrophage influx. METHODS: We studied the expression of osteopontin protein and mRNA in renal donor biopsies (N = 7) and renal transplant biopsies with cyclosporine A toxicity (N = 23) by immunohistochemistry and in situ hybridization. Serial tissue sections were immunostained with a monocyte/macrophage marker, CD68, to demonstrate the pattern of macrophage infiltration. RESULTS: Strong osteopontin expression was observed in the majority of pretransplant donor biopsies in the absence of any macrophage infiltration. In the biopsies with cyclosporine toxicity, osteopontin expression was widespread and demonstrated moderate immunohistochemical signal intensity that did not correlate with the number of interstitial macrophages present. CONCLUSIONS: Strong osteopontin protein and mRNA expression by tubular epithelium was observed in pretransplant donor biopsies and in biopsies with cyclosporine toxicity without an inflammatory cell infiltration. Therefore, osteopontin expression alone is insufficient to serve as the principal mediator of intrarenal monocyte/macrophage influx in the transplant setting.
Biopsy, Needle↗
Licensure of the cardiac sonographer: an overview of issues and activities.
The impact of echocardiography on the continuum of cardiovascular health care is well established. Ongoing concerns regarding costs, accessibility, quality, and appropriateness of services rendered by practitioners of echocardiography have prompted various legislative proposals and regulatory policies from government, medical professional groups, and health plans. Specifically, there continues to be a drive to enact law for licensure of sonographers. These activities require continuing advocacy for the profession with active leadership. As part of its mission statement, the American Society of Echocardiography (ASE) states, "ASE strives to be a leader in public policy in order to create a favorable environment for excellence in the practice of echocardiography." As such, the ASE is committed to an increase in their interaction with legislators, payers, and policy makers. This article describes the historical perspective of state, federal, and provincial sonographer licensure issues to provide an understanding of the political perspectives.
Allied Health Personnel↗
A pilot project to assess the methodological issues involved in evaluating acupuncture as a treatment for disabling breathlessness.
OBJECTIVES: This pilot study explores the methodological implications of evaluating the use of acupuncture in the treatment of disabling breathlessness. DESIGN: A randomized, controlled trial involving three treatments that were used on one occasion, each in random order. SETTINGS: The study was designed to evaluate the feasibility of providing acupuncture treatment on a domiciliary basis, in Southampton (United Kingdom) to patients with disabling breathlessness. SUBJECTS: Sixteen (16) subjects with disabling breathlessness caused by chronic lung disease (primarily chronic obstructive pulmonary disease [COPD]) were recruited from the respiratory medicine clinics of Southampton University Hospitals Trust. INTERVENTIONS: The treatments were real acupuncture, dummy acupuncture, and mock transelectrical nerve stimulation (TENS). OUTCOMES: To evaluate the respiratory outcome measures, to look at the credibility of the three treatments (using a previously validated Borkovec and Nau scale), and to calculate the sample size for a larger, more definitive study. RESULTS: Twelve (12) subjects completed the study. The acupuncture was a predefined point prescription that had been found previously to be of value in this condition, an approach that could be taught to health professionals and provided on a domiciliary basis. The treatment was provided only on one occasion, therefore, we did not expect a clear therapeutic benefit to emerge, but some nonsignificant benefit was noted as a consequence of acupuncture treatment. The shuttle test that we used as an objective measure of breathlessness was impractical in a domiciliary environment and will not be used in further studies. Each of the three treatments was equally credible at the outset, although real and dummy acupuncture were considered by the patients to be preferable choices after the completion of treatment. CONCLUSIONS: It was possible to carry out this study on a domiciliary basis. The information obtained will allow us to design a much clearer definitive study and the small, but statistically insignificant, response to acupuncture has allowed us to estimate sample size.
Acupuncture Therapy↗
Parenting styles, regimen adherence, and glycemic control in 4- to 10-year-old children with diabetes.
OBJECTIVE: To examine relationships among parenting styles, regimen adherence, and glycemic control for preschool and elementary school children who have Type I diabetes. METHODS: Parents of 55 children with diabetes completed parenting style and regimen adherence questionnaires. Glycosylated hemoglobin results were collected by chart review. RESULTS: Parental warmth was associated with better adherence ratings. Regression analyses showed that parental warmth explained 27% of the variance in adherence ratings. Parental restrictiveness was associated with worse glycemic control in univariate analyses. However, only Black ethnicity, not adherence or parenting variables, predicted glycemic control. Black ethnicity and lower socioeconomic status (SES) were associated with more parental restrictiveness and worse glycemic control. CONCLUSIONS: These results suggest that authoritative parenting, characterized by support and affection, may be advantageous for the regimen adherence and glycemic control of school-age and younger children with diabetes. Demographic characteristics are important and require further study in this context.
Child↗
Receiving a diagnosis of lung cancer: patients' interpretations, perceptions and perspectives.
Lung cancer has a higher incidence than any other type of cancer and more than 80% of sufferers die within a year of diagnosis. An important aspect of caring for cancer patients is the breaking of bad news, something that most doctors admit to having difficulty with. Only a few publications on this issue adopt the patients' perspective. This study aimed to document patients' views on delivery of lung cancer diagnoses, their attitudes to methods used and ideas for improvement. Patients were selected from medical, surgical and general practitioner clinics to provide insight into patients' perceptions of care in different environments. Those who gave informed consent completed a taped semi-structured interview. Transcripts were analysed qualitatively using a phenomenological approach. Recruitment was stopped when saturation was reached: no new themes were being identified. A summary of results was sent to patients, whenever possible, for their comment. An independent researcher coded four transcripts to establish the degree of inter-rater reliability. Thirteen patients were recruited. There were five key areas: communication (including the use of words such as 'tumour' and 'growth'), family/community issues, reaction to diagnosis, views on treatment and prognosis (all of which were very variable), and suggested improvements (e.g. a clearer explanation of the experience of bronchoscopy in the patient information leaflet, PIL). Inter-rater reliability was good. The PIL is being revised. Factors including family situation and personal experience of illness vary greatly and yet they influence patients' reactions to receiving a diagnosis of lung cancer, their interpretation of this and their attitudes to the illness and treatment. These findings underline the need to continue to develop lung cancer services that can provide quality care tailored to each patient.
Aged↗
Microscopic observation and processing validation of fruit sanitizing treatments for the enhanced microbiological safety of fresh orange juice.
Studies were conducted to evaluate the infiltration of dye and bacteria into the interior of orange fruit and the impact of possible infiltration on achieving a 5-log microbial reduction during fresh juice processing. Fresh orange fruit were treated at the stem end area with dye and either Salmonella Rubislaw or Escherichia coli strains expressing green fluorescent protein. Microscopic images showed that bacterial contaminants localized at the surface or near surface areas that may be sanitized by surface treatments. Dye infiltration was not a reliable indicator of bacterial penetration in citrus fruit. To quantify the reduction of bacterial contamination, orange fruit were inoculated with E. coli and processed with and without hot water treatments. Greater than 5-log reductions were achieved in juice extracted from fruit immersed in hot water for 1 or 2 min at 80 degrees C, in comparison to the E. coli level detected in the control juice obtained by homogenization of inoculated fruit.
Beverages↗
The p20 gene product of Citrus tristeza virus accumulates in the amorphous inclusion bodies.
Citrus tristeza virus (CTV) has 10 3' open reading frames (ORFs) of unknown function except for the two coat proteins. The highest produced subgenomic RNAs are those of the major coat protein gene (p25) and the 3' most genes, p20 and p23. The proteins from three ORFs, p25, p27, and p20, were examined in the yeast two-hybrid assay for the interactions between themselves and to one another. The p20 protein exhibited a high affinity for itself, suggesting that it might aggregate in infected cells. The cytopathology of CTV infections includes characteristic paracrystalline and amorphous inclusions in the phloem elements of infected citrus. Polyclonal antiserum raised against the bacterial expressed p20 gene product detected a protein of approximately 22-23 kDa, which accumulated to relatively high levels in CTV-infected citrus, but not in healthy citrus. Immunogold localization using antibodies to p20 protein showed strong and specific labeling of the amorphous inclusion bodies present in CTV-infected cells. Mesophyll protoplasts of Nicotiana benthamiana transfected with a CTV mutant containing the green fluorescent protein (GFP) ORF fused in-frame to the 3' end of p20 protein ORF expressed high levels of GFP. The fusion protein was concentrated in one specific area in the cytoplasm and lacked an organized shape. Accumulation of high levels of p20 protein in infected tissue, specific localization of the p20-GFP fusion protein, immunolocalization of p20 protein into amorphous inclusions, and strong homologous p20 protein-p20 protein interactions in the yeast-two-hybrid assay suggest that the p20 protein of CTV is a major component of the amorphous inclusion bodies present in CTV-infected cells.
Blotting, Western↗
Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants.
BACKGROUND: Concerns have been raised about emergence of ganciclovir resistance as a result of the advent of both routine oral ganciclovir prophylaxis and highly potent immunosuppression. We retrospectively assessed the occurrence of ganciclovir-resistant cytomegalovirus disease among transplant recipients who had received oral ganciclovir prophylaxis and highly potent immunosuppression. METHODS: We studied 240 recipients of liver, kidney, or pancreas transplants. Antiviral susceptibility testing of blood cytomegaloviral isolates was done when patients failed to respond to intravenous ganciclovir treatment for symptomatic cytomegalovirus infection. Portions of the UL97 gene associated with ganciclovir resistance were sequenced in cytomegalovirus isolates with phenotypic resistance to ganciclovir. FINDINGS: Ganciclovir-resistant cytomegalovirus disease developed in five (7%) of 67 seronegative recipients of cytomegalovirus-seropositive organs (D+/R-) compared with none of 173 seropositive recipients (p=0.002). Among the 25 (10.4%) patients who developed cytomegalovirus disease within 1 year after transplantation, five had ganciclovir-resistant cytomegalovirus disease. Among D+/R-transplant recipients, ganciclovir-resistant cytomegalovirus disease was more common among the group receiving the most potent immunosuppression--ie, recipients of kidney and pancreas or pancreas alone (four of 19) compared with all other transplant recipients (one of 48, p=0.02). Ganciclovir-resistant cytomegalovirus disease was diagnosed at a median of 10 months after transplantation (range 7-12) after lengthened exposure to ganciclovir, was associated with previously described mutations of the UL97 gene, and led to serious clinical complications. INTERPRETATION: Ganciclovir-resistant cytomegalovirus is an important cause of late morbidity among D+/R- transplant recipients who have had lengthened exposure to ganciclovir and have received highly potent immunosuppression. Strategies to reduce this complication, especially among D+/R- patients, are warranted.
Adult↗
Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures.
The purpose of this study was to explore possible calculations using oral glucose tolerance test (OGTT) values in order to develop a simple measure of insulin sensitivity. We devised a formula for an insulin sensitivity index, ISI(0,120), that uses the fasting (0 min) and 120 min post-oral glucose (OGTT) insulin and glucose concentrations. It appears to be generalizable across a spectrum of glucose tolerance and obesity. Most importantly, our data show that ISI(0,120) correlates well, when applied prospectively in comparative studies, with the insulin sensitivity index obtained from the euglycemic hyperinsulinemic clamp (r = 0.63, P < 0.001). This correlation was demonstrably superior to other indices of insulin sensitivity such as the HOMA formula presented by Matthews, and performed comparably to the computerized HOMA index. Measurement of insulin sensitivity has traditionally been possible only in research settings because of the invasiveness and expense of the methods used. Clinical investigators have therefore sought more practical methods to obtain an index of insulin sensitivity. Such an index should approximate insulin sensitivity as measured by the euglycemic hyperinsulinemic clamp (M). We present ISI(0,120), a simple yet sensitive measure of insulin sensitivity which is adaptable for use in clinical settings as well as large epidemiologic studies.
Adolescent↗
Can oral midazolam predict oral cyclosporine disposition?
Effective cyclosporine therapy is confounded by large interindividual differences in oral bioavailability and a narrow therapeutic window. Because cytochrome P450 (CYP) 3A-mediated first-pass metabolism contributes to this unpredictable bioavailability, an in vivo oral CYP3A phenotyping probe could be a valuable tool in optimizing cyclosporine therapy. Based on similarities in the metabolic kinetics of cyclosporine and midazolam by the liver and intestinal mucosa, we evaluated whether midazolam oral clearance would predict cyclosporine oral clearance when the two drugs were administered to 20 medically stable kidney transplant recipients. Despite earlier findings in liver transplant recipients who displayed a strong correlation between the systemic clearances of midazolam and cyclosporine, there was a weak correlation between their oral clearances in the current group of subjects (r(s)=0.50, P=0.03). Differing extents of intestinal first-pass metabolic extraction between the two drugs, inhibition of midazolam metabolism by cyclosporine at the level of the intestine, and/or P-glycoprotein-mediated intestinal efflux of cyclosporine (but not midazolam) may account for this poor correlation. We conclude that although oral midazolam is unlikely to be clinically useful as a probe for cyclosporine disposition, its utility in the prediction of other orally administered CYP3A substrates cannot be out ruled.
ATP Binding Cassette Transporter, Subfamily B, Mem↗