30 research outputs found
Effect of growth hormone replacement therapy in a boy with Dent's disease: a case report
<p>Abstract</p> <p>Introduction</p> <p>Dent's disease is an X-linked recessive proximal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis and progressive renal failure. To the best of our knowledge, this is only the third report on the use of growth hormone therapy in a child with poor growth associated with Dent's disease.</p> <p>Case presentation</p> <p>We report on a 7-year-old Montenegrin boy with proteinuria, hypercalciuria, nephrocalcinosis, rickets and short stature with unimpaired growth hormone secretion. A molecular genetic analysis showed S244L substitution on the CLCN5 gene. After two years of conventional treatment with hydrochlorothiazide, laboratory tests revealed more prominent proteinuria, mild hypophosphatemia, increased values of alkaline phosphatase and features of rickets. Phosphate salts, calcitriol, potassium citrate and growth hormone were included in the therapy. After three years of therapy, his adjusted parental stature was 1.53 standard deviations higher than at the initiation of growth hormone therapy. His global kidney functions and levels of proteinuria and calciuria remained relatively stable. In spite of the growth hormone therapy, his tubular reabsorption of phosphate deteriorated.</p> <p>Conclusion</p> <p>Treatment with recombinant human growth hormone may have a positive effect on final height in poorly growing children with Dent's disease and hypophosphatemic rickets. However, it is not possible to reach definite conclusions due to the small sample within the literature and the brief duration of the therapy.</p
Transduction of Surface and Basal Cells in Rhesus Macaque Lung Following Repeat Dosing with AAV1CFTR
The ClC-5 knockout mouse model of Dent's disease has renal hypercalciuria and increased bone turnover.
Dent's disease is a nephrolithiasis disorder associated with hypercalciuria and low molecular weight proteinuria that is caused by mutations in the voltage-gated chloride channel ClC-5. Because the exact cause of hypercalciuria in this disease is unknown and could come from a renal, intestinal, or bone origin, we have investigated overall calcium handling in the ClC-5 knockout mouse (ClC-5 KO). On a high calcium diet, ClC-5 KO mice had elevated serum 1alpha,25-dihydroxyvitamin D3 (1alpha,25D3), alkaline phosphatase (AP), osteocalcin (OC), and urinary deoxypyridinoline (DPD), but serum parathyroid hormone (PTH), calcium, and intestinal calcium uptake was similar to that of wild-type (WT) mice. A 30-fold decrease in dietary calcium intake caused elevation of serum PTH and urinary cyclic adenosine monophosphate in ClC-5 KO mice and decreased the renal calcium excretion, which still remained 2-fold above that of WT mice. On this low calcium diet, both groups of mice had the same serum 1alpha,25D3, with similar increments in intestinal calcium absorption, serum AP, OC, and urinary DPD. These data indicate that the hypercalciuria in the ClC-5 KO mice on low and high calcium diets is of bone and renal origin and is not caused by increased intestinal calcium absorption, despite an elevated serum 1alpha,25D3. These mice data suggest that young patients with this disease may have a propensity for altered bone homeostasis that should be monitored clinically
A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea
BACKGROUND: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID). METHODS: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1–2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4 mg then 8 mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements. RESULTS: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio=2.0, 90% confidence interval: 0.9–4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P=0.05) and at the 8-mg dose level (P=0.02) compared with placebo. CONCLUSION: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted
Efficacy and safety of AZD6244 (ARRY-142886) as second/third-line treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)
WNK4 kinase regulates surface expression of the human sodium chloride cotransporter in mammalian cells
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Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function?
Forty-eight BALB/c mice were divided into two groups of 24 animals each. In the control group (CTRL) saline was intratracheally instilled, while the virus group (VR) received rAAV2-GFP (4
×
10
9 particles). These groups were subdivided into four sub-groups (
n
=
6). Pulmonary mechanical parameters were analyzed after 3 weeks (VR1d3w) and at 1 (VR2d1w), 2 (VR2d2w) and 3 weeks (VR2d3w) after a second AAV2 dose. Fractions of the area of alveolar collapse and the amount of polymorpho- and mononuclear cells were determined by point-counting technique. Viral transduction was evaluated by immunohistochemistry. Lung mechanical data were similar in all groups. However, there was an increase in airway and lung parenchyma cellularity and in the fraction of area of alveolar collapse in the VR2d2w group, which nonetheless decreased with time. There was no evidence of apoptosis in any group. In conclusion, the gene transfer vector AAV2 induces, in the lung, a discrete inflammatory reaction that does not affect either baseline lung mechanics or airway hyperresponsiveness