Persistent hypocalcaemia in a Chinese girl due to a novel de-novo activating mutation of the calcium-sensing receptor gene.

A significant proportion of patients formerly diagnosed with idiopathic hypoparathyroidism actually have activating mutation of the calcium-sensing receptor (CaSR) gene. Awareness of the possibility of activating mutation of CaSR gene in patients with sporadic idiopathic hypoparathyroidism is important because of its relevance to clinical management. This report is of a novel activating mutation of the CaSR gene identified in a 10-year-old Chinese girl who was initially diagnosed as having idiopathic hypoparathyroidism at 6 years of age after presenting with seizures. Her serum calcium level was difficult to maintain near the lower limit of normal despite treatment with high-dose calcitriol. Treatment with calcitriol produced significantly elevated urinary calcium-to-creatinine ratio. Direct sequencing of the CaSR gene showed a novel heterozygous mutation (p.Q735P (c.2204A>C)). Molecular genetic analysis of her parents demonstrated that both parents did not harbour the child's mutation, indicating that her mutation had arisen de novo.

Effects of celecoxib in human retinoblastoma cell lines and in a transgenic murine model of retinoblastoma.

BACKGROUND/AIM: Celecoxib, a cyclooxygenase-2 inhibitor and antiangiogenic agent, has demonstrated potent anticancer effects in preclinical studies and in human clinical trials. To evaluate the potential utility of this agent in the treatment of retinoblastoma, the authors investigated the effects of celecoxib in retinoblastoma cell lines and in a murine model of this disease. METHODS: Growth inhibitory effects of celecoxib were evaluated in Y79 and Weri-RB1 human retinoblastoma cell lines by WST-1 cell proliferation assay. For animal study, two groups of 24, 8 week old LHbeta-TAg transgenic mice were treated with celecoxib (250 mg/kg, orally once a day) or vehicle control, 5 days/week for 6 weeks. Mice were sacrificed on day 43. Enucleated eyes were serially sectioned and ocular tumour burden was quantified by histopathological analysis. RESULTS: Celecoxib did not inhibit proliferation of Y79 or Weri-RB1 cells, even at concentrations far exceeding clinically achievable levels. No significant difference in ocular tumour burden between celecoxib treated and control mice (p=0.73) was found. CONCLUSION: Celecoxib was ineffective at inhibiting proliferation of retinoblastoma cells in vitro and was ineffective at controlling retinoblastoma tumour growth in a murine model of this disease. On the basis of these findings, oral celecoxib therapy is unlikely to have clinical utility in the treatment of retinoblastoma.

Mortality in SLE nephritis.

In a review of 112 patients with SLE nephritis treated between 1976 and 1982, 31 were known to have died. Renal failure (32.2%) was the commonest cause of death. Gastrointestinal haemorrhage (16%), infections (12.8%) and central nervous system involvement (6.5%) were important causes of death. Thirteen out of 17 patients dying in the presence of renal failure had initially presented with renal impairment. Renal biopsies in 16 patients who have died showed diffuse proliferative glomerulonephritis in all except 1 patient, and uraemia was the commonest cause of death in these patients. Pregnancies terminating in abortions were followed by complications in 5 patients. Discontinuation of steroid therapy by patients was followed by complications, and ended in death in 6 patients.