Dilatative uropathy as a manifestation of neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin-II gene.

Polydypsia and polyuria are frequent symptoms in patients with sellar masses caused by neurohypophyseal diabetes insipidus. Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI), a disorder caused by mutations in the arginine vasopressin (AVP) -neurophysin II (NPII) gene, should be considered as a rare differential diagnosis. A delayed diagnosis bears the risk of life-threatening electrolyte imbalances and permanent urinary tract damage, leading to impaired quality of life.We present a Caucasian kindred of at least 4 generations with FNDI.Clinical histories, endocrine para-meters, and results of molecular analyses of the AVP gene are presented with a review of the literature on diabetes insipidus (DI) related urinary tract dilatation.Polyuria and polydipsia were only reported based on explicit and thorough interrogation after more than 4 years of clinical follow-up. A novel heterozygous mutation in the AVP gene was found in all examined symptomatic subjects (c.1-33_c.4del37nt). A literature review revealed that non-obstructive hydronephrosis (NOH) is a rare but known complication of DI.Since increased fluid intake is often a typical familial pattern in adFNDI, it is frequently missed as being pathologic in affected patients, therefore a detailed clinical history of drinking volumes is of critical importance. AVP gene testing is an important component in the confirmation of the diagnosis. Otherwise unexplainable NOH should lead to further investigations and evaluation of rare diseases like FNDI.

[Regional coordination of paediatric oncological care in northwestern Lower Saxony, Germany--network funded by health insurance companies]. / Verbund PädOnko Weser-Ems--Regionale ambulante Versorgung pädiatrisch-onkologischer Patienten aus der Weser-Ems-Region im Rahmen einer Integrierten Versorgung.

The cure rates in pediatric oncology have been substantially improved due to standardized treatment strategies and centralization of therapy. Close clinical and hematological monitoring is mandatory for patients between periods of chemotherapy for early detection and treatment of therapy-related complications such as infections. This results in frequent and time-consuming outpatient examinations for the patient and family at the oncological center in order to evaluate clinical condition and hematological findings. In widespread regions such as the Weser-Ems area in northwest Lower Saxony, Germany, the long distances between patients' home and the oncological center lead to higher risks and impairment of quality of life (QoL) for the patients and their families. Accordingly, in 2001 pediatric hospitals and practices, patient care services and patients' support groups in Weser-Ems founded a network (Verbund PädOnko Weser-Ems). The "Verbund PädOnko" aims at coordinated, high-quality regional outpatient patient treatment in order to reduce risks of long-distance transports to reach the oncological center. Since 2005 a newly established mobile care team realized 1 443 home visits covering a total of 150 300 km. Since 2007 the network has been funded by health insurance organisations. Internal and external benchmarking was performed showing that the rate of short term inpatient treatments were reduced. Treatment quality was assured and the QoL of the patients and their families was improved through the work of the network. The "Verbund PädOnko Weser-Ems" network represents a promising prototype model for the regional coordination of outpatient treatment and care of patients with rare diseases in wide spread areas.

Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL-BFM 95 reinduction treatment.

Repeated asparaginase treatment has been associated with hypersensitivity reactions against the bacterial macromolecule in a considerable number of patients. Immunological reactions may range from anaphylaxis without impairment of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase activity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction treatment was performed prospectively in 76 children with newly diagnosed acute lymphoblastic leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol, 10 000 U/m2 body surface area of native Escherichia coli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 45/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginase activity were not available from the remaining 31 patients, but information with regard to hypersensitivity reactions only was given. Eighteen out of 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/l for at least 14 d was determined in 43 of the 45 patients who were analysed for enzyme activity.

Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols.

Hypersensitivity reactions are relevant adverse effects of asparaginase therapy. Therefore, children treated with native Escherichia coli asparaginase in induction therapy of acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL) were switched to the pegylated enzyme for reinduction under drug monitoring. Seventy children, including four patients with allergic reactions during induction, were given one dose of Oncaspar 1,000 U/m2 intravenously. Activity was determined every third or fourth day until it dropped below the limit of quantification. In current reinduction protocols [ALL/NHL-Berlin-Frankfurt-Münster (BFM) 95 trials], four doses of 10,000 U/m2 E. coli asparaginase deplete asparagine for about 2-3 weeks, therefore activities of >/= 100 U/l up to day 14 and >/= 50 U/l up to day 21 were targeted. In 66 patients without an allergic reaction during induction, the mean activity was 606 +/- 313 U/l, 232 +/- 211 U/l and 44 +/- 50 U/l after 1, 2 and 3 weeks respectively. In 44/66 patients, activity was >/= 100 U/l after 14 d. A rapid decline in activity was seen in the remaining 22 patients, including 8/22 patients who showed no activity after 1 week. Toxicity was low and comparable to the native enzymes but, in contrast to about 30% of hypersensitivity reactions with conventional reinduction therapy, no allergic reaction was seen. Substituting 4 x 10,000 U/m2 asparaginase medac for one dose of 1,000 U/m2 Oncaspar was safe and well tolerated. Comparable pharmacokinetic treatment intensity was achieved in about two-thirds of patients.

Secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy.

Secondary neoplasms (SNs) represent serious late complications after successful treatment of malignant diseases. To evaluate the rate and type of SNs after Berlin-Frankfurt-Münster (BFM) treatment in children with acute lymphoblastic leukemia (ALL), we analyzed the data from the BFM database and the German Childhood Cancer Registry (GCCR). Between April 1979 and April 1995, 5006 children with B-precursor or T-ALL were enrolled in 5 ALL-BFM multicenter trials. The median follow-up time from diagnosis was 5.7 years (range 1.5-18 years). By December 1997, 52 SNs were documented, including 16 acute myeloid leukemias (AMLs), 13 neoplasms of the central nervous system (CNS), and 23 other neoplasms. Compared with the expected numbers estimated from incidence rates derived from the GCCR, this represented a 14-fold increase for all cancers and a 19-fold increase for CNS tumors. SNs developed 0.9 to 15 years (median: 6 years) after the diagnosis of ALL; 46 patients were in first complete remission (CR). The overall cumulative risk of SNs at 15 years was 3.3% (95% confidence interval [CI]: 1.6%-5.1%) and 2.9% (95% CI: 1.6%-4.2%) in first CR. The risk was 3.5% (95% CI: 1.5%-5. 5%) after treatment, including cranial irradiation and significantly lower in nonirradiated patients: 1.2% (95% CI: 0.2%-2.3%; P =.048). The development of secondary AML was not associated with the use of any specific cytotoxic agent. Considering the high-survival rate of this large unselected ALL cohort, the risk of SN is relatively low, though higher, especially after cranial irradiation, than in the general population. Long-term follow-up is mandatory, and further SNs with longer latency periods are to be expected. (Blood. 2000;95:2770-2775)