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Biomedical subjects

S L Fan

Publications and source records attributed to S L Fan.

9 recordsLinked to original sources

Recurrence of Wegener's granulomatosis 13 years after renal transplantation.

Wegener's granulomatosis (WG) can cause renal failure, requiring long-term renal replacement therapy. Renal transplantation in patients with WG is successful, but the risk for recurrence of the disease necessitates continued vigilance. We report a patient that originally presented with acute renal failure secondary to a pauci-immune focal necrotizing crescentic glomerulonephritis. Subsequent nasal involvement and serologic tests for antineutrophil cytoplasmic antibodies suggested a diagnosis of WG.

Antibodies, Antineutrophil Cytoplasmic↗

Bisphosphonates in renal osteodystrophy.

The present review considers the role that bisphosphonates might have in patients with renal failure. Although bisphosphonates are widely used to reduce fracture risk in patients with osteoporosis, few studies have documented their effect in patients with renal osteodystrophy. The pathogenesis of bone loss after renal transplantation and the role of the recently identified osteoprotegerin/receptor activating nuclear factor-kappaB system is described. Inhibition of bone resorption may prove beneficial when high bone turnover is present, but there are potential drawbacks to widespread use of bisphosphonates. These issues are discussed, with emphasis placed on reports published within the past 18 months.

Animals↗

Pamidronate therapy as prevention of bone loss following renal transplantation.

BACKGROUND: Very rapid bone loss, osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion. Glucocorticoids, cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions. Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented, or at least attenuated, by pamidronate and other bisphosphonates. METHOD: We prospectively studied 26 male patients undergoing renal transplantation, and randomized them to receive either placebo or intravenous pamidronate (0.5 mg/kg) at the time of transplantation and again one month later. All patients received immunosuppression comprising prednisolone, cyclosporine and azathioprine. The bone mineral density (BMD) of the second, third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry (DXA). RESULTS: Twelve months after transplantation, the mean (+/- SEM) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4% (P < 0.05). In contrast, patients who received pamidronate experienced no significant reduction of BMD at the lumbar vertebrae. At the femoral neck, placebo-treated patients showed a reduction of BMD of 9% (P < 0.005), whereas there was no significant change in the pamidronate treated group. The two study groups had similar patient profiles, serum parathyroid hormone (PTH) and aluminium concentrations. After transplantation, comparable falls in the serum creatinine and PTH concentration were found in the two groups. Apart from transient hypocalcemia in two patients, no significant adverse effects of pamidronate were noted. CONCLUSION: This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later. The regimen was simple to administer, well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients.

Absorptiometry, Photon↗

Potent suppression of the parathyroid glands by hydroxylated metabolites of dihydrotachysterol(2).

BACKGROUND: Dihydrotachysterol(2), a licensed pharmaceutical, is hydroxylated to 25-hydroxydihydrotachysterol(2) (25(OH)DHT(2)) and 1 alpha,25-dihydroxydihydrotachysterol(2) (1 alpha,25(OH)(2)DHT(2)) in man. We have compared the biological activity of these metabolites with calcitriol and the 'non-calcaemic' analogue, 22-oxacalcitriol (OCT) in bovine parathyroid cell cultures and in rats. METHODS: The effect of each sterol on parathyroid hormone (PTH) secreted by primary bovine parathyroid cells was measured. High-performance liquid chromotography and gas chromotography-mass spectrometry were used to investigate in vitro 25(OH)DHT(2) metabolism. Rats were given a single intraperitoneal injection or five daily injections of each sterol, and changes in ionized calcium and PTH were measured. RESULTS: In vitro, all sterols suppressed PTH significantly. Calcitriol and OCT were of similar potency, but 1 alpha, 25(OH)(2)DHT(2) and 25(OH)DHT(2) required higher concentrations to suppress PTH equally. We were unable to detect metabolism of 25(OH)DHT(2) to 1 alpha,25(OH)(2)DHT(2) in vitro. In rats, a single dose of 0.5 microg/rat of calcitriol increased ionized calcium at 30 and 40 h (statistically significant at 48 h). 50 microg of OCT and 1 alpha,25(OH)(2)DHT(2) did not cause significant hypercalcaemia at 48 h, although 1 alpha,25(OH)(2)DHT(2) caused hypercalcaemia at 30 h. In contrast, 50 microg of 25(OH)DHT(2) caused hypercalcaemia at 48 h but not at 30 h. Five daily doses of 0.001 microg/rat of calcitriol caused a significant rise in calcium and a 50% fall in PTH. OCT and 1 alpha,25(OH)(2)DHT(2) at 0.025 and 0.5 microg/rat respectively caused similar suppression of PTH but without hypercalcaemia. CONCLUSION: 1 alpha,25(OH)(2)DHT(2) and 25(OH)DHT(2) are potent suppressors of PTH in vitro and in vivo. 25(OH)DHT(2) may be active by virtue of its pseudo-1 alpha-hydroxyl group. Hypercalcaemia caused by a single dose of 1 alpha,25(OH)(2)DHT(2) appeared to be more transient than calcitriol. Five daily doses of 1 alpha, 25(OH)(2)DHT(2) and OCT could achieve 50% suppression of PTH without significant increments in ionized calcium. In contrast, suppression of PTH by calcitriol was associated with significant increments in ionized calcium. These data suggest that like OCT, 1 alpha, 25(OH)(2)DHT(2) can dissociate calcaemic actions from parathyroid-suppressing actions in a manner that may be therapeutically useful.

Animals↗

Membranous nephropathy complicating adenolymphoma of the parotid (Warthin's tumour).

Membranous nephropathy has been described in association with many malignancies including various lymphomas. However, it has not been previously described as a complication of benign solid adenolymphoma of the parotid, also called Warthin's tumour. We describe a patient who presented with an adenolymphoma of the parotid, and developed a severe nephrotic syndrome due to membranous nephropathy 6 months after the parotid swelling. The nephrotic syndrome resolved following parotidectomy and a short course of immunosuppression with prednisolone and cyclophosphamide. The possible pathophysiologic mechanisms are discussed.

Adenolymphoma↗

Transesophageal low-energy cardioversion in an animal model of life-threatening tachyarrhythmias.

The purpose of this study was to determine the feasibility and efficacy of terminating life-threatening ventricular tachyarrhythmia by low-energy synchronous or asynchronous shocks delivered through a transesophageal catheter that had both an anode and a cathode. Forty-three episodes of ventricular fibrillation or flutter (Vf or VF) were provoked by transesophageal asynchronous random shocks occurring during the vulnerable period of the ventricular cycle in seven dogs and seven pigs that were healthy adults. The 43 episodes of Vf or VF were terminated by the transesophageal technique. The defibrillation energy thresholds were 23.11 +/- 6.28 J (range, 5-30 J). Seven episodes of ventricular tachycardia (VT) with a cycle length of 360 msec or less (330 +/- 27 msec) were provoked by ventricular pacing stimuli during acute myocardial ischemia resulting from delayed resuscitation in two dogs and three pigs. Five of the seven VTs had a duration of 31 seconds or more, and they were all terminated by transesophageal synchronous shocks, the cardioversion thresholds being 1.71 +/- 2.25 J (range, 0.25-5 J). Fourteen episodes of idioventricular tachycardia (IVT) with a cycle length of 400 msec or more (445 +/- 33.5 msec) spontaneously occurred after the use of adrenaline and after defibrillation in four dogs and five pigs. We also succeeded in terminating seven episodes of IVT with a duration of 34 seconds or more by the same means of treating VT, although IVT is not an indication for cardioversion in the clinical setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗