Biomedical subjects

Nicole Graf

Publications and source records attributed to Nicole Graf.

5 recordsLinked to original sources

PubMed2006

Nephrotoxicity with cyclooxygenase 2 inhibitor use in children.

The nephrotoxic potential of anti-inflammatory drugs alone and in compound preparations has been known for over fifty years. Nephrotoxicity associated with selective cyclooxygenase 2 (COX-2) inhibitor use is reported in adult patients but not in children. We present here the first report of reversible acute renal failure associated with the COX-2 inhibitor rofecoxib (Vioxx) in three children. Patient 1, an 18 month old girl with neonatal Bartter syndrome, developed acute renal failure with a peak creatinine of 1.9 mg/dl (164 micromol/l) and severe hyperkalemic metabolic acidosis. Patient 2, a 14 year old boy with a history of rheumatic fever, developed acute renal failure with a peak creatinine of 2.7 mg/dl (240 micromol/l). While patient 3, a healthy 14 year old girl, developed acute renal failure and tubulointerstitial nephritis confirmed on renal biopsy with a peak creatinine of 3.3 mg/dl (287 micromol/L). All children had been taking non-selective non-steroidal anti-inflammatory drugs (NSAID's) immediately prior to rofecoxib use. Renal function returned to normal within one week in all three patients and has remained normal at follow-up. This paper highlights the nephrotoxic risk of COX-2 inhibitor use in the pediatric population.

Acute Kidney Injury↗

PubMed2006

A cutaneous allergen neutralisation test that correlates with the duration of venom immunotherapy.

BACKGROUND: Despite the well-documented efficacy of Hymenoptera specific immunotherapy (SIT), there is no safe method to reliably characterise the patient level of protection. Only poor correlations between protection and allergen-specific serum immunoglobulins have been found, and a sting challenge is the only means to evaluate the efficacy of immunotherapy. Therefore, we aimed to develop a cutaneous test that measures in vivo neutralisation of the Hymenoptera venom. MATERIALS AND METHODS: Twenty-four patients with wasp venom allergy were included in the study. Wasp-specific serum IgE, IgG and IgG4 were measured by ImmunoCAP. Dilutions of the individual patient sera were intradermally injected into the forearm. Then, wasp venom extract was injected into these sites to quantitatively assess the formation of wheals and flares. RESULTS: The results show that during the course of SIT, patient sera gained the capacity to neutralise skin reactions to wasp venom extracts in vivo. The test correlated with the duration of SIT as well as with the concentration of IgG and IgG4. CONCLUSION: The in vivo neutralisation test may become a promising tool in allergy diagnostics as well as in monitoring the success of SIT in patients undergoing allergen SIT.

Adult↗

PubMed2005

Aqueduct stenosis-?Benign.

'Benign' aqueduct stenosis is a common cause of hydrocephalus in the paediatric population and is frequently treated by endoscopic third ventriculostomy. Occasionally, aqueduct stenosis can be a prelude to the development of other pathology, as is seen in these two cases of pineal tumours developing in patients whose hydrocephalus was successfully treated with endoscopic third ventriculostomy. The case histories are presented, along with the recommendation for increased radiological screening of patients with this usually 'benign' presentation.

Brain Neoplasms↗

PubMed2005

Congenital central hypoventilation syndrome and Hirschsprung's disease in an extremely preterm infant.

Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is a rare disorder with a variable phenotypic severity. The underlying cause is thought to be an abnormality of neural crest development and/or migration. Surviving neonates can have generalized autonomic nervous system dysfunction. Recent reports have identified mutations in the PHOX2B gene in a significant number of patients with this disorder. Diagnosis and management of this disorder in the setting of extreme prematurity is difficult as the manifestations of failure to maintain breathing effort and failure to establish feeds overlap with the complications of prematurity. We describe an infant who had congenital central hypoventilation syndrome with Hirschsprung's disease and was delivered at 26 weeks' gestational age and had total aganglionosis of the bowel, failure to wean from ventilation, and a mutation in the PHOX2B gene.

Cell Lineage↗

PubMed2004

Prophylactic bilateral nephrectomies in two paediatric patients with missense mutations in the WT1 gene.

BACKGROUND: Denys-Drash syndrome (DDS) is associated with mutations of the Wilms' tumour 1 (WT1) gene, and is characterized by pseudohermaphroditism, a progressive glomerulopathy, and the development of Wilms' tumour. More than 90% of patients with DDS who carry constitutional intragenic WT1 mutations are at high risk (90%) for the development of Wilms' tumour. WT1 is a signalling protein with 90% of WT1 mutations occurring in the WT1 zinc finger region as single nucleotide polymorphisms, the majority of which are missense mutations. METHODS: Constitutional DNA was extracted from peripheral blood. Direct sequencing and restriction enzymes were employed to analyse mutations. RESULTS: Two children, 46XY males who had evidence of pseudohermaphroditism, hypogonadism and renal failure with a glomerulopathy atypical for DDS, but no Wilms' tumour or nephroblastomatosis, on investigation, prior to transplant, were identified with missense mutations in the WT1 gene, in exons 8 and 9, respectively. The decision to do prophylactic nephrectomies was based on the genetic identification of WT1 mutations supporting a diagnosis of incomplete DDS, with the potential for increased risk of malignancy with the development of Wilms' tumour. The nephrectomy specimens demonstrated nephrogenic rests (nephroblastomatosis), which have a potential for malignant transformation. CONCLUSIONS: WT1 missense mutations in exons 8 and 9 can be regarded as having the potential for malignant change supporting prophylactic nephrectomy in apparent incomplete DDS patients with end-stage renal disease.

Child↗