Background: Urinary concentration impairment is a major feature of cyclosporine nephrotoxicity. Methods: We explored two possible mechanisms that may underlie cyclosporineinduced polyuria; water, and/or osmotic diuresis. Cyclosporine was subcutaneously injected to normal salt-fed Sprague-Dawley rats at a daily dose of 25mg/kg for 2 weeks (Experiment I) and 7.5mg/kg for 6 weeks (Experiment II). Results: In Experiment I, cyclosporine treatment caused an increase in urine volume (2.7±0.5 vs. 10.3±1.13mL/d/100 g BW, p<0.001) and a decrease in urine osmolality (2,831±554 vs. 1,379±478mOsm/kg H2O, p<0.05). Aquaporin-2 (AQP2) protein expression decreased in cyclosporine-treated rat kidneys (cortex, 78±8%, p<0.05; medulla, 80±1%, p<0.05). Experiment II also showed that urine volume was increased by cyclosporine treatment (4.97±0.66 vs. 9.65±1.76mL/d/100 g BW, p<0.05). Whereas urine osmolality was not affected, urinary excretion of osmoles was increased (7.5±0.4 vs. 14.9±1.4mosmoles/d/100 g BW, p<0.005). Notably, urinary excretion of glucose increased in cyclosporine-treated rats (7±1 vs. 10,932±2,462 mg/d/100 g BW, p<0.005) without a significant elevation in plasma glucose. In both Experiment I and II, GLUT2 protein expression in the renal cortex was decreased by cyclosporine treatment (Experiment I, 55±6%, p<0.005; Experiment II, 88 ±3%, p<0.05). Conclusion Both water diuresis and osmotic diuresis are induced by cyclosporine nephrotoxicity. AQP2 and GLUT2 downregulation may underlie water and osmotic diuresis, respectively.

Background: Urinary concentration impairment is a major feature of cyclosporine nephrotoxicity. Methods: We explored two possible mechanisms that may underlie cyclosporineinduced polyuria; water, and/or osmotic diuresis. Cyclosporine was subcutaneously injected to normal salt-fed Sprague-Dawley rats at a daily dose of 25mg/kg for 2 weeks (Experiment I) and 7.5mg/kg for 6 weeks (Experiment II). Results: In Experiment I, cyclosporine treatment caused an increase in urine volume (2.7±0.5 vs. 10.3±1.13mL/d/100 g BW, p<0.001) and a decrease in urine osmolality (2,831±554 vs. 1,379±478mOsm/kg H2O, p<0.05). Aquaporin-2 (AQP2) protein expression decreased in cyclosporine-treated rat kidneys (cortex, 78±8%, p<0.05; medulla, 80±1%, p<0.05). Experiment II also showed that urine volume was increased by cyclosporine treatment (4.97±0.66 vs. 9.65±1.76mL/d/100 g BW, p<0.05). Whereas urine osmolality was not affected, urinary excretion of osmoles was increased (7.5±0.4 vs. 14.9±1.4mosmoles/d/100 g BW, p<0.005). Notably, urinary excretion of glucose increased in cyclosporine-treated rats (7±1 vs. 10,932±2,462 mg/d/100 g BW, p<0.005) without a significant elevation in plasma glucose. In both Experiment I and II, GLUT2 protein expression in the renal cortex was decreased by cyclosporine treatment (Experiment I, 55±6%, p<0.005; Experiment II, 88 ±3%, p<0.05). Conclusion Both water diuresis and osmotic diuresis are induced by cyclosporine nephrotoxicity. AQP2 and GLUT2 downregulation may underlie water and osmotic diuresis, respectively.

Three cases of hisiocytic medullary reticulosis occurring in children aged 6 years, 9 years and 14 years, are described. In all children the diagnosis was based on anemia, granulocytopenia, thrombocytopenia and marked erythrophagocytosis by bone marrow and lymph node atypical histiocytes. They all showed immediate remission with combined chemotherapy of vinblastine and prednisolone, but Case 1 eventually died at 6 months after onset of this rapidly progressive, fatal illness and Case 2, 3 are alive 14 months after onset of their illness.
Agranulocytosis ; Anemia ; Bone Marrow ; Child ; Diagnosis ; Drug Therapy ; Histiocytes ; Humans ; Lymph Nodes ; Prednisolone ; Thrombocytopenia ; Vinblastine

Background: Ingestion of foreign bodies leading to impaction at the pharynx and oesophagus have been extensively described in English literatures. However, impactions at the gastrointestinal tract distal to the oesophagus are less commonly encountered due to the more capacious luminal diameter as it approaches the stomach. While intentional foreign body ingestions impacted distal to the oesophagus are often more complicated, literatures on the management of these distal oesophageal impactions are scarce. Case presentation: We present five cases of foreign body impaction at varying sites of gastrointestinal tract beyond the oesophagus, contrasting management approach comparing the role of endoscopy, open surgery and conservative management. Cases presented include patients aged 40 to 70 with intentional foreign bodies ingestion. The first case described a cerebral palsy patient with pica who had to undergo difficult evacuation under anaesthesia followed by colonoscopy; the second and third cases presented 2 different schizophrenic patients with 2 differing management approach. The second case was managed with multiple operations due to complications and died eventually, making the only mortality in our case series; whereas the third case was managed conservatively with acceptable outcome after multiple laparotomies prior. Fourth and fifth cases described 2 body packers who swallowed tobacco and 2 phones, respectively; the former was uneventfully managed conservatively, the latter, had to undergo surgical extraction. Individualized approach to these distal impactions of ingested foreign bodies are described with a review of available literatures which are tabulated and discussed in this case series. Conclusion Endoscopy, surgery, conservative management and sometimes a combination of approaches are utilised for the management of foreign bodies impacted distal to the oesophagus, especially in complex and recurrent cases. Decision, timing and approach of extraction must be individualised with consideration of risk weighed against the benefit of each intervention over the other