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Grahame Elder

Publications and source records attributed to Grahame Elder.

5 recordsLinked to original sources

Meta-analysis of biochemical and patient-level effects of calcimimetic therapy.

BACKGROUND: Many randomized trials have now evaluated the effects of calcimimetics in patients with chronic kidney disease and secondary hyperparathyroidism (SHPT) on standard therapy with vitamin D and/or phosphate binders. We conducted a meta-analysis to evaluate outcomes of therapy with these novel agents. METHODS: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and conference proceedings were searched for randomized controlled trials evaluating any calcimimetic against placebo or another agent in predialysis or dialysis patients with chronic kidney disease. Data were extracted for all relevant patient-centered and surrogate outcomes. Analysis was by means of a random-effects model, and results are expressed as relative risk or weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: Eight trials (1,429 patients) were identified that compared a calcimimetic agent plus standard therapy with placebo plus standard therapy. End-of-treatment values for parathyroid hormone (4 trials; 1,278 patients; WMD, -290.49 pg/mL; 95% CI, -359.91 to -221.07), serum calcium (3 trials; 1,201 patients; WMD, -0.85 mg/dL; 95% CI, -1.14 to -0.56), serum phosphorus (3 trials; 1,195 patients; WMD, -0.29 mg/dL; 95% CI, -0.50 to -0.08), and calcium x phosphorus product (3 trials; 1,194 patients; WMD, -7.90 mg2/dL2; 95% CI, -10.25 to -5.54) were significantly lower with calcimimetic therapy compared with placebo. No significant effects on patient-based end points were shown. CONCLUSION: Calcimimetic treatment of patients with SHPT leads to significant improvements in biochemical parameters that observational studies have associated with increased mortality, cardiovascular risk, and osteitis fibrosa, but patient-based benefits have not yet been shown. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until additional randomized trials become available.

Aniline Compounds↗

Pheochromocytoma and functional paraganglioma syndrome: no longer the 10% tumor.

Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors of the sympathetic nervous system, while head and neck paragangliomas are non-secreting tumors of parasympathetic origin. Recent developments in clinical and molecular research on these tumor forms have significantly clarified their genetic backgrounds and challenged the view of "pheochromocytoma as the 10% rule tumor." Firstly, a larger proportion of these tumors are today discovered in normotensive patients during imaging carried out for other reasons than suspicion of pheochromocytoma. Secondly, although the differential diagnosis between malignant and benign tumors remains a challenge, the risk of malignancy well exceeds the classical 10% in patients with extra-adrenal disease, and/or carriers of germ-line SDHB mutations. Finally, up to a third of patients carry a germ-line mutation in a gene predisposing to pheochromocytoma and/or paraganglioma. Identification of a constitutional mutation in RET, VHL, SDHD, or SDHB has implications for clinical screening and follow-up for both the patient and for relatives at risk who can be identified by screening for the same mutation. Genetic testing in apparently sporadic cases is therefore regarded as beneficial, especially in patients diagnosed before 50 years of age, and in patients with bilateral, multifocal, malignant and/or extra-adrenal disease.

Abdominal Neoplasms↗

Pathophysiology and recent advances in the management of renal osteodystrophy.

Bone disease is observed in 75-100% of patients with chronic renal failure as the glomerular filtration rate (GFR) falls below 60 ml/minute. Hyperparathyroid (high turnover) bone disease is found most frequently followed by mixed osteodystrophy, low-turnover bone disease, and osteomalacia. With advancing renal impairment, "skeletal resistance" to parathyroid hormone (PTH) occurs. To maintain bone turnover, intact PTH (iPTH) targets from two to four times the upper normal range have been suggested, but whole PTH(1-84) assays indicate that amino-terminally truncated fragments, which accumulate in end-stage renal disease (ESRD), account for up to one-half of the measured iPTH. PTH levels and bone-specific alkaline phosphatase (BSAP) provide some information on bone involvement but bone biopsy and histomorphometry remains the gold standard. Calcitriol and calcium salts can be used to suppress PTH and improve osteomalacia but there is growing concern that these agents predispose to the development of vascular calcification, cardiovascular morbidity, low-turnover bone disease and fracture. Newer therapeutic options include less calcemic vitamin D analogues, calcimimetics and bisphosphonates for hyperparathyroidism, and sevelamer for phosphate control. Calcitriol and hormone-replacement therapy (HRT) have been shown to maintain bone mineral density (BMD) in certain patients with end-stage renal disease (ESRD). After renal transplantation, renal osteodystrophy generally improves but BMD often worsens. Bisphosphonate therapy may be appropriate for some patients at risk of fracture. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and the careful use of an increasing number of effective therapies can reduce the morbidity associated with this common problem.

Biopsy↗