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Biomedical subjects

Nilesh Shah

Publications and source records attributed to Nilesh Shah.

10 recordsLinked to original sources
PubMed2006

Anaemia after renal transplantation--role of immunosuppressive drugs and a pathophysiological appraisal.

Improvements in patient care and longevity on dialysis programmes together with the increased numbers of patients referred for renal replacement therapy will inevitably result in enlarging numbers of subjects with functioning renal transplants. While this translates to a boon for the patients in terms of survival and quality of life, a very real problem has begun to emerge, that of post-transplantation anaemia (PTA). The prevalence of this condition has been estimated by several studies as varying somewhere between one third and two thirds of all patients, with the same attendant problems as anaemia in the context of chronic kidney disease. PTA is multifactorial in origin and involves interplay between a number of risk factors, not least of all the immunosuppressive protocol. It is the purpose of this article to briefly review the contribution from transplant immunosuppression to PTA and to assess its likely effects on and treatment options for patients.

Anemia↗
PubMed2006

Posttransplantation anemia in adult renal allograft recipients: prevalence and predictors.

BACKGROUND: Management of anemia is an important factor in the care of patients with chronic kidney disease as the anemic state can confer significant morbidity and mortality. Posttransplantation anemia (PTA) has received comparatively less attention in the literature, and the prevalence and predictors of PTA vary between different studies. The purpose of this study was to investigate a large posttransplant population from 3 centres in the UK to elucidate the point prevalence of PTA, its determinants and the use of erythropoiesis stimulating agents (ESA) in these patients. METHODS: All adult patients with functioning renal transplants and attending renal transplant outpatients at Guy's, King's College, or St. Helier Hospitals, London, as of 31/12/2004 who had a valid hemoglobin in the previous 3 months, and who were more than 3 months postengraftment, were identified. Patients' notes and electronic patient records were obtained and a detailed cross-sectional clinical and biochemical database was constructed. The data were analyzed for the point prevalence of PTA, the prevalence of ESA use and for determinants of hemoglobin. The WHO criteria were used to define anemia and all patients on treatment with an ESA was classified as anemic irrespective of hemoglobin. RESULTS: A total of 1,511 (947 male) patients were studied. Mean age was 48.1+/-13.7 years with no difference between the sexes. Mean time posttransplantation was 8.5+/-7.2 years and mean estimated MDRD GFR was 47.6+/-18.9 ml/min with a higher GFR in males (49.9+/-19.0 v 43.8+/-18.0 mL/min, P<0.0001). Mean hemoglobin in the studied population was 12.9+/-1.6 g/dl with a significantly higher level among males than females (mean 13.3+/-1.6 v 12.3+/-1.4 g/dl, P<0.0001). The prevalence of anemia was 45.6% with a prevalence of 44.1% among males and 48.1% amongst females. Severe anemia was present in 50 subjects (3.3% of the total cohort). One hundred and forty-five patients (9.6% of the entire cohort) were being treated with an ESA. Of these subjects, 41 did not meet WHO criteria for the definition of anemia. After multiple regression analyses, age, female sex, renal function and to a lesser extent serum ferritin and therapy with angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (both negatively associated) were predictive of hemoglobin. CONCLUSIONS: The prevalence of anemia posttransplantation was high while comparatively few patients were being treated with erythropoiesis stimulating agents. The strongest predictors of hemoglobin in this cohort of patients were age, female sex and allograft function. Medical therapy with MMF and sirolimus was associated with a high prevalence of anemia but this was likely to be the result of poorer graft function in these subjects who mostly had chronic allograft nephropathy. A large interventional prospective study with valid control groups is now needed to assess the long-term contributions of clinical and biochemical factors of renal function and to elucidate the effects of therapy on outcome.

Adult↗
PubMed2006

Post-transplantation anaemia in adult and paediatric renal allograft recipients-Guy's Hospital experience.

BACKGROUND: The commonest cause of renal transplant loss is death with a functioning graft, usually from an excess of cardiovascular disease (CVD). Anaemia is becoming increasingly recognized as a reversible risk factor for the development of CVD. The purpose of this study was to estimate the prevalence of post-transplantation anaemia (PTA) in a large population of stable adult and paediatric renal transplants in one centre and to correlate the estimated glomerular filtration rate (eGFR), iron indices and the use of immunosuppressants with the prevalence of anaemia. METHODS: Every adult and paediatric patient with a functioning renal transplant and more than 3 months post-engraftment at Guy's hospital, London, as of 31 December 2004 and who had a valid creatinine and haemoglobin, in the period 1 September-31 December 2004 inclusive, was identified. A large database of clinical and biochemical indices was built up on the basis of medical notes and electronic patient records. Results were analysed for the prevalence of anaemia and risk factors for its development. Anaemia was defined according to the WHO criteria. All patients on treatment with an erythropoiesis stimulating agent were classified as anaemic, irrespective of haemoglobin. RESULTS: A total of 878 adults and 73 children were identified. Mean haemoglobin in adults was 12.9 +/- 1.6 g/dl and 11.8 +/- 1.4 g/dl in the children. Mean eGFR was 49.3 +/- 20.1 ml/min in adults and 65.7 +/- 18.8 ml/min in the paediatric cohort. Haemoglobin correlated positively with the eGFR in both cohorts (R = 0.33 and 0.29 in adults and children, respectively (P < 0.0001 for both)). We identified anaemia in 45.3% of adults and 22% in children. Ferritin levels were lower in children than in adults (79 +/- 93 vs 204 +/- 353 mg/l), but were higher in both cohorts among the non-anaemic populations than in those with anaemia. 58% of adults taking mycophenolate mofetil (MMF) were anaemic compared with 22% of children. One child, and 68 adults, were on recombinant erythropoietin. Multiple regression analyses identified age, female gender, eGFR and serum ferritin levels as independent predictors of haemoglobin in adult subjects. CONCLUSIONS: The prevalence of PTA was high in both adult and paediatric cohorts while comparatively few patients were being treated with erythropoiesis stimulating agents. The strongest predictors of haemoglobin in this cohort of patients were age, female sex and graft function. Immunosuppression including MMF or sirolimus was associated with a higher prevalence of anaemia, but this was likely to be the result of poorer graft function in these subjects. Iron deficiency did not seem to be a causative factor for anaemia in this population.

Adult↗
PubMed2006

Novel arylpyrazole compounds selectively modulate glucocorticoid receptor regulatory activity.

The activities of intracellular receptors are regulated by their cognate ligands. Here we show that a series of related arylpyrazole compounds, which specifically bind the glucocorticoid receptor (GR), selectively modulated GR-regulated biological functions in preadipocyte, pre-osteoblast, and lung epithelial cell lines. Indeed, when we monitored 17 endogenous GR target genes in one of these cell types, we found that distinct arylpyrazole compounds induced different expression patterns. We showed by chromatin immunoprecipitation that the arylpyrazole compounds regulated, in a gene-specific manner, either GR occupancy of the genomic glucocorticoid response element (GRE) or events after GR association, such as histone modification. Overall, our results establish that subtle differences in ligand chemistry can profoundly influence the transcriptional regulatory activity of GR, and that endogenous genes bearing natural GREs are especially sensitive detectors of these differences.

3T3-L1 Cells↗
PubMed2006

Anemia after renal transplantation.

Anemia in the setting of chronic kidney disease is a well-recognized phenomenon that is associated with decreasing renal function and deficiency of or resistance to erythropoietin. However, anemia in the post-renal transplantation setting has received comparatively less attention in the literature. In this review, we aim critically to appraise the available literature regarding posttransplantation anemia, concentrating in particular on the prevalence of posttransplantation anemia, its etiopathogenesis, potential effects on morbidity and mortality, and the rationale for intervention and treatment. Despite deficiencies in the literature, we conclude that posttransplantation anemia is a common phenomenon that can occur either early or late posttransplantation, and its causation is usually multifactorial and includes contributions notably from poor or decreasing renal function, immunosuppression, and iron deficiency. Conversely, there is a shortage of well-conducted prospective studies looking at the morbidity attributable to posttransplantation anemia and a lack of trial evidence to determine whether intervention improves patient morbidity and outcome.

Anemia, Iron-Deficiency↗
PubMed2006

Cortical blindness associated with electroconvulsive therapy.

BACKGROUND: Neurological syndromes arising in the context of electroconvulsive therapy (ECT) have rarely been reported in literature. METHODS: We report an adult man who received ECT during a manic episode and who developed prolonged confusion and transient (1 day) bilateral loss of vision immediately after the eighth treatment. RESULTS: Except for the blindness and the patient's lack of awareness of the symptom, the neurological examination was within normal limits. No abnormality was evident on brain computed tomographic scan. These findings suggest the diagnosis of cortical blindness. The patient was able to see normally when he awoke the next morning. He had complete amnesia for the events of the previous day. CONCLUSION: Transient cortical blindness is probably a very rare adverse effect of ECT. The findings are discussed in the context of visual impairment associated with epileptic seizures.

Adult↗
PubMed2005

RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization.

Loss of RUNX3 expression is suggested to be causally related to gastric cancer as 45% to 60% of gastric cancers do not express RUNX3 mainly due to hypermethylation of the RUNX3 promoter. Here, we examined for other defects in the properties of RUNX3 in gastric cancers that express RUNX3. Ninety-seven gastric cancer tumor specimens and 21 gastric cancer cell lines were examined by immunohistochemistry using novel anti-RUNX3 monoclonal antibodies. In normal gastric mucosa, RUNX3 was expressed most strongly in the nuclei of chief cells as well as in surface epithelial cells. In chief cells, a significant portion of the protein was also found in the cytoplasm. RUNX3 was not detectable in 43 of 97 (44%) cases of gastric cancers tested and a further 38% showed exclusive cytoplasmic localization, whereas only 18% showed nuclear localization. Evidence is presented suggesting that transforming growth factor-beta is an inducer of nuclear translocation of RUNX3, and RUNX3 in the cytoplasm of cancer cells is inactive as a tumor suppressor. RUNX3 was found to be inactive in 82% of gastric cancers through either gene silencing or protein mislocalization to the cytoplasm. In addition to the deregulation of mechanisms controlling gene expression, there would also seem to be at least one other mechanism controlling nuclear translocation of RUNX3 that is impaired frequently in gastric cancer.

Animals↗
PubMedDate not supplied

Cannulated screw fixation of Jones fractures: a clinical and biomechanical study.

BACKGROUND: Traditional nonsurgical treatment of Jones fractures has high rates of delayed union, nonunion, and refracture. Internal fixation has become the treatment of choice in athletes and active patients. PURPOSE: The purpose of this study was (1) to review the short- and long-term clinical results of cannulated screw fixation of Jones fractures and (2) to perform a biomechanical evaluation of fatigue failure characteristics of several types of screws used in the fixation of Jones fractures. STUDY DESIGN: Retrospective case series and in vitro biomechanical study. METHODS: Ten male and 5 female patients with Jones fractures fixed with cannulated screws ranging from 4 mm to 6.5 mm in diameter were evaluated by chart review, review of radiographs, and telephone interview. Mean follow-up from surgery to phone survey was 34 months. Screws ranging in size from 2.7 mm to 7.3 mm, both cannulated and noncannulated, stainless steel and titanium, were tested in the laboratory by cyclic loading to 250 N up to a maximum of 200,000 cycles. RESULTS: Mean time to healing as shown on radiographs and by full activity after surgery were 7.3 and 7.9 weeks, respectively. All patients were able to return to their previous levels of activity. Screw fatigue data showed that the number of cycles to failure increased with increasing screw diameter. For 4-mm screws, mean number of cycles to failure was 4308 for cannulated titanium screws, 22,012 for cannulated stainless steel screws, and 44,523 for noncannulated stainless steel screws. CONCLUSIONS: In our patients, cannulated screw fixation of Jones fractures was a procedure that was reliable, had low morbidity, and afforded athletes a quick return to activity. CLINICAL RELEVANCE: The laboratory study suggests that the largest screw possible should be used for surgical fixation of these fractures and that screws less than 4 mm in diameter should be used with caution.

Adolescent↗