[Long-term experience with Cohen ureteral reimplantation in bilateral vesicoureteral reflux in childhood]. / Langzeiterfahrungen mit der Ureterozystoneostomie nach Cohen beim bilateralen vesikoureterorenalen Reflux im Kindesalter.

INTRODUCTION: In bilateral VUR, Cohen cross-trigonal ureteric reimplantation is a popular but also controversial surgical approach. We present our own experience in a retrospective analysis. PATIENTS AND METHODS: Between 1990 and 2005, 41 children (26 girls, 15 boys) with bilateral reflux [92 renal units (RU)] underwent ureteric reimplantation. The mean age was 4.5 (0.3-12) years. Eight patients had ureteral duplication (six unilateral, two bilateral); 12 of 41 patients had no intraoperative ureteral stenting. Seven patients had prior surgery for VUR. A successful result was defined as absence of VUR, significant UVJ obstruction, or voiding dysfunction throughout the follow-up. RESULTS: The mean follow-up was 7.8 (0.5-15) years. Eight patients (19.5%) had 13 complications. One patient had an intraoperative small bowel lesion (2%). Six patients (14.6%) had UTI. Four patients (9.8%) showed transient UVJ obstruction. Three required a temporary percutaneous nephrostomy. Two of these patients had no intraoperative ureteral stenting. Recurrence of VUR was found in 2 patients (4.8%) and 2/92 RU (2.2%), respectively. Complications were more frequent in high-grade VUR, ureter duplex, or unstented ureteral reimplantation. Prior surgery for VUR did not influence the postoperative outcome. Postoperative voiding disorders were not observed. CONCLUSIONS: Two unilateral recurrences of VUR were observed, requiring a reoperation in one patient. A reoperation for UVJ obstruction was not necessary. Related to 92 RU the surgical success rate was 97.8%. Intraoperative ureteral stenting has to be considered with respect to the current discussion of shortening inpatient procedures. In our experience, the perioperative risk was elevated in patients with high-grade VUR or ureteral duplication.

Neonatal-onset multisystem inflammatory disease (NOMID) due to a novel S331R mutation of the CIAS1 gene and response to interleukin-1 receptor antagonist treatment.

Neonatal-onset multisystem inflammatory disease (NOMID) is due to mutations in the CIAS1 gene. We describe the case of a 5-year-old boy with neonatal onset of urticaria-like rash, chronic fever, laboratory findings of systemic inflammation, hepatosplenomegaly, and chronic CNS inflammation associated with sensorineural deafness. Sequence analysis of exon 3 of the CIAS1 gene revealed a novel C1754A/S331R mutation. Since experimental evidence suggests that patients with cryopyrin-associated periodic syndromes (CAPS) could respond to inhibition of binding of interleukin IL-1alpha and IL-1beta to the IL-1 receptor type 1, we treated the child with the IL-1 receptor antagonist anakinra. A remarkable clinical and serological response to therapy was observed, suggesting that pharmacological inhibition of the IL-1 signaling pathway offers an important new treatment option for patients with NOMID.

Genetic variations of the SLC7A9 gene: allele distribution of 13 polymorphic sites in German cystinuria patients and controls.

Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3A1 gene cause type I cystinuria, patients with non-type I cystinuria carry mutations in the SLC7A9 gene. Both gene products form the renal amino acid transporter rBAT/b0,+AT affected in cystinuria. In the present study a total of 59 patients with different ethnic background were screened for sequence variations in SLC7A9, out of these 32 were of German origin. For determination of allele frequencies of detected polymorphisms, 58 healthy German controls were investigated. Molecular-genetic analysis was performed using single-strand conformation polymorphism analysis, restriction assays and sequencing. Allele frequencies were analyzed statistically for the detected polymorphisms. In addition to the 6 already known variants we identified 7 new polymorphisms. Statistical analyses showed a significantly different distribution of alleles between German patients and German controls in case of the polymorphisms c. 147C>T (exon 2), c.386C>T (exon 3), IVS3+22T>G, c.584C>T (exon 4), c.610T>C (exon 4), c.692C>T (exon 5), c.852C>A (exon 6) and c.872C>T (exon 6). In summary, our results show that cystinuria is a complex disease which is not only caused by mutations in SLC7A9 and SLC3A1, but also influenced by other modifying factors such as variants in SLC7A9.

[Case report: neonatal hypertension]. / Kasuistik: neonatale arterielle Hypertonie.

BACKGROUND: Neonatal arterial hypertension is rare with an incidence between 0.2 - 3 %. Clinical presentation varies widely and is in some cases dramatic. PATIENT: A 4-day old full-term neonate was admitted to the intensive care unit with severe congestive heart failure and metabolic acidosis. Mechanical ventilation was initiated and dobutamine administered because of poor systolic function. Continuous monitoring of blood pressure revealed severe arterial hypertension (30 to 40 mm Hg above the 95th percentile). Ultrasonography showed an echogenic left kidney with normal perfusion. Laboratory examinations revealed a raised peripheral renin activity, thrombocytopenia, slightly raised d-dimers, a microhematuria and mild proteinuria. After resolution of hypertension under therapy with an ACE-inhibitor, a MAG3 renal scan showed complete absence of renal function on the left side. Renal artery stenosis was excluded by venous transcardial angiography. Under therapy with Captopril, the patient was discharged and followed up for 8 months. He is developing normally with normal serum creatinine (0.4 mg/dl), but low renal function (17 %) of the left side as assessed by DMSA-scan and compensatory right kidney hypertrophy are observed. DISCUSSION: Diagnosis and treatment of neonatal hypertension are discussed with respect to the proposed case. After exclusion of other causes we conclude that a perinatal microangiopathic event may have lead to the renal lesions with malignant renovascular hypertension.

Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome.

Testolactone is used to treat conditions with excessive estrogen synthesis, e.g. gonadotropin-independent precocious puberty in McCune-Albright syndrome (MAS). Unfortunately, daily treatment with testolactone requires 3 to 4 doses (10-20 tablets) and even at these doses it is sometimes ineffective. We treated a patient with MAS (café-au-lait spots; thelarche at age 2- 6/12 yr; menarche at 5- 5/12 yr; accelerated bone age [BA 10 yr]) with the highly selective aromatase inhibitor anastrozole (1 mg once per day). Tamoxifen 1 mg/kg per day was added for 1 year but was discontinued when an ovarian cyst developed with markedly elevated estradiol levels. Estradiol levels returned to normal after resuming anastrozole-only treatment and accelerated BA progressed only 6 months during 2 1/2 years of treatment. The potent estrogen suppressive action and simple dosage regimen of anastrozole suggest it may be advantageous compared to other aromatase inhibitors such as testolactone or anti-estrogens.

Bladder dysfunction in children with bilateral single ectopic ureters.

BACKGROUND: Single ectopic ureters are a rare malformation in children. Therapy consists of ureteral reimplantation. However, in case of bilateral single ectopic ureters, subsequent malformation of the bladder trigone and bladder neck may result in additional voiding dysfunction, and ureteral reimplantation alone may not solve the urologic problems. METHODS: The authors report their experience with 2 girls, in whom bilateral single ectopic ureters were treated by ureteral reimplantation in early childhood and who did not gain adequate bladder control during following years. RESULTS: Videourodynamic evaluation was done in both girls. No bladder overactivity was found during the urodynamic studies. However, cystography showed a widely open bladder neck during filling with no sufficient bladder neck closure shown by urethral pressure profile studies. When blocking the bladder outlet by balloon catheters, adequate bladder filling volume was achieved. Incontinence was cured by implantation of an AMS 800 artificial sphincter system in a 10-year-old girl. A 7-year-old girl was regarded to be too young for sphincter implantation and is waiting for surgery within the next years. CONCLUSION: Insufficient development of trigone and bladder neck with subsequent urinary incontinence has to be kept in mind when deciding on surgical procedures in children with bilateral single ectopic ureters.

[Ektopic ureter - a not considered cause of persisting enuresis in girls]. / Ektoper Ureter - eine verkannte Ursache des Einnässens bei Mädchen.

BACKGROUND: Ectopic ureter - especially in a duplicated collecting renal system - is a specific cause of incontinence in young girls. Although the symptom of continuous dribbling of urine is characteristic for this malformation, diagnosis is often delayed, as the possibility of ectopic ureters is not considered in treating girls with delayed toilet training. CASE REPORT: We present the case of a young girl with a variety of unnecessary invasive diagnostic and therapeutic procedures due to a misunderstood "enuresis", before incontinence was cured by upper pole heminephrectomy. CONCLUSIONS: Girls, who never have been dry and who loose urine all the time do have an ectopic ureter, unless evidence to the contrary has been put forward. Only considering the possibility of ectopic ureters will avoid unnecessary diagnostic and therapeutic procedures in these girls.

[The iodine supply of newborns. Comparison of iodine absorption and iodine excretion of mother and child]. / Die Jodversorgung von Neugeborenen. Vergleich der Jodaufnahme und Jodausscheidung von Mutter und Kind.

BACKGROUND: Since 1989 the use of iodized salt has been allowed in Germany, additional supplementation with iodide tablets has been recommended during pregnancy and lactation. This study was undertaken to clarify whether the iodine intake of neonates and young infants improved since then. PATIENTS AND METHODS: In the first part of the study the urinary iodine excretion of 52 newborns and their mothers in 1998 was compared to data of similar studies 1983 in the area of Göttingen and 1982 in the areas of Heidelberg and Rothenburg, Germany. All these are geographically low-iodine areas. In the second part the iodine supply of infants in 1998-1999 under feeding with mother's milk or formulas in 1998 and 1999 was obtained by measuring iodide concentrations in urine and milk using a high pressure liquid chromatography (HPLC) method. RESULTS: 45% of pregnant women were without iodide supplementation in 1998. In 1998 the median urinary iodide concentration during the first week of life was 4.3 micrograms/dl, which was more than twice that found in 1983 (1.75 micrograms/dl). Infants feeding by mother's milk without maternal iodine supplementation or by semi-elementary diet had the lowest urinary iodine excretion, whereas significantly higher values were measured when feeding formulas for term or preterm infants. CONCLUSIONS: The iodine intake of newborns has markedly improved during 15 years. The WHO criterias for adequate iodine supply (TSH < 5 microU/ml and urinary iodine >/ = 10 micrograms/dl) were only partly fulfilled in Göttingen indicating that a mild iodine deficiency still exists with the risk of iodine deficiency disorders.

Immunoscintigraphy (BW 250/183) in neonates and infants with fever of unknown origin.

Fever of unknown origin is defined as a temperature above 39.0 degrees C together with a white blood cell count > or = 15,000 mm-3, the duration of fever exceeding 2 weeks and a correct diagnosis not being obtained in the first week of hospitalization. In neonates and infants with fever of unknown origin, the localization of the infectious focus is often difficult and unsatisfactory. In this retrospective study, the clinical value of 99Tcm-labelled antigranulocyte antibodies for this group of patients was investigated. Thirty-two immunoscintigrams were performed using 185-259 MBq 99Tcm-labelled antigranulocyte antibodies (BW 250/183) in 30 neonates and infants (21 boys, 9 girls, mean age 29.4 +/- 2 months), who had fever of unknown origin. Immunoscintigraphy was carried out as whole-body images (n = 7) or single planar images (n = 25) 4 h and 24 h post-injection. In children with known cardiac failure, single photon emission tomography of the thorax was performed to diagnose endocarditis (n = 2). For verification, the results of the immunoscintigrams were compared with radiology (conventional radiography = 14, MRI = 5, CT = 3), biopsy (n = 2), blood culture (n = 10) and clinical follow-up after specific therapy. In 11 of 30 children (36%), the diagnosis of an infective focus was possible with immunoscintigraphy. The sensitivity and specificity of diagnosing infective foci was 72% and 95% respectively (n = 11; colitis = 2, infection of the central permanent catheter tip = 2, middle ear infection = 1, spondylitis/discitis = 3, osteomyelitis = 2, umbilical infection = 1). In vertebral body infections, all lesions were photopenic. In 18 children (60%), no infective focus was found on immunoscintigraphy. In this group of children, the main reason (n = 5) for fever of unknown origin was chronic juvenile rheumatoid arthritis. No uptake was seen in two infants with cardiac failure and suspected endocarditis on SPET. In 3 of the 18 patients (17%), localization of an infective focus was not possible with immunoscintigraphy or on other examinations. In these patients, the fever disappeared spontaneously after a few days of antibiotic therapy. In conclusion, we have shown that 99Tcm-anti-NCA-95 scanning is a safe method with a high sensitivity and specificity for detecting infectious foci in neonates and infants with fever of unknown origin. Furthermore, this method is easy to perform, since no withdrawal of blood is necessary.

[123I-scintigraphy and perchlorate depletion test in the diagnosis of congenital hypothyroidism]. / 123I-Szintigraphie und Perchlorat-Depletionstest bei der Diagnostik der kongenitalen Hypothyreose.

AIM: Thirty eight children suffering from congenital primary permanent hypothyroidism were studied to determine the diagnostic impact of 123I scintigraphy in comparison to laboratory findings and ultrasonography. METHODS: In all patients 123I scintigraphy was performed after intravenous administration of 3.7 MBq 123I. If accumulation of the radiotracer in thyroid tissue occurred a perchlorate discharge test was performed subsequently. RESULTS: Scintigraphy revealed athyrosis in 7 children. In 9 children a lingual thyroid was observed. Deficiency in iodine organification was diagnosed by a significant discharge of 123I in 15 patients. In four of these children the diagnosis of Pendred's syndrome could be established. Ectopic thyroid tissue could be demonstrated only by scintigraphy where clinical examination and sonography failed in the diagnosis in all cases. Hypoplasia of the thyroid gland as it was diagnosed in 2 cases by ultrasonography appeared to be unlikely because a normal 123I uptake was seen in these patients. In 2 patients with scintigraphic proven athyrosis an orthotopic gland had been falsely considered by ultrasound. In 44% of our patients the final diagnosis could only be established if 123I scintigraphy and perchlorate discharge test were performed. CONCLUSION: This findings suggest that scintigraphy is indispensible in the correct diagnostic work up of congenital hypothyroidism.

[Microproteinuria and enzymuria in fever and pyelonephritis in childhood. A prospective study of 180 children]. / Mikroproteinurie und Enzymurie bei Fieber und Pyelonephritis im Kindesalter. Eine prospektive Untersuchung an 180 Kindern.

In 180 children (87 children belonging to a control group, 68 with fever of non-renal origin, and 25 with pyelonephritis) albumin and immunoglobulin G (markers for glomerular dysfunction), alpha-1-microglobulin and beta-NAG (markers for proximal tubular dysfunction) and apolipoprotein A1 (marker of "postrenal' dysfunction) were measured in second-voided morning urine. In children with fever of non-renal origin, glomerular dysfunction was encountered in 8.8%, tubular dysfunction in 17.6% and mixed glomerular-tubular dysfunction in 14.7% of cases. Among children with pyelonephritis, 28% revealed glomerular dysfunction and 44% mixed glomerular-tubular dysfunction. No case of solitary proximal tubular dysfunction was observed in children with pyelonephritis. There were highly significant differences in presence and expression of glomerular dysfunction between children with fever of non-renal origin and children with pyelonephritis (P < 0.0001), whereas with regard to proximal tubular dysfunction, the differences were only moderately significant (beta-NAG: P < 0.01) or of low significance (alpha-1-microglobulin: P < 0.05). This may indicate that morphologic changes occur during interstitial pyelonephritis due to inflammation of glomeruli, resulting in glomerular dysfunction, while proximal tubular dysfunction may additionally be due to fever-associated function processes.

Diagnostic value of 123iodine scintigraphy and perchlorate discharge test in the diagnosis of congenital hypothyroidism.

AIM: Forty children suffering from congenital primary permanent hypothyroidism were studied to determine the diagnostic impact of 123I scintigraphy in comparison to laboratory findings and ultrasonography. METHODS: In all patients 123I scintigraphy was performed after intravenous administration of 3.7 MBq 123I. If accumulation of the radiotracer in thyroid tissue occurred a perchlorate discharge test was performed subsequently. RESULTS: Scintigraphy revealed athyrosis in 7 children. In 11 children a lingual thyroid was observed. Deficiency in iodine organification was diagnosed by a significant discharge of 123I in 15 patients. In four of these children the diagnosis of Pendred's syndrome could be established. Ectopic thyroid tissue could be demonstrated only by scintigraphy where clinical examination and sonography failed in the diagnosis in all cases. Hypoplasia of the thyroid gland as it was diagnosed in 2 cases by ultrasonography appeared to be unlikely because a normal 123I uptake was seen in these patients. In 2 patients with scintigraphic proven athyrosis an orthotopic gland had been considered by ultrasound. In 50% of our patients the final diagnosis could only be established if 123I scintigraphy and perchlorate discharge test were performed. CONCLUSION: This findings suggest that scintigraphy is indispensible in the correct diagnostic work up of congenital hypothyroidism.

Autoimmune thyreoiditis in childhood--epidemiology, clinical and laboratory findings in 61 patients.

Autoimmune thyroiditis (AT) is the most common cause of nonendemic goiter and acquired hypothyroidism in children and adolescents. In 61 patients AT was diagnosed following clinical, ultrasonographic, biochemical and cytological examinations. Girls were more often affected than boys, the female/male ratio in our patients was 9:1. Clinically the vast majority of patients had a goiter. Approximately half of the patients were euthyroid (n = 29). In the other patients hyperthyrotropinaemia (n = 16), hypothyroidism (n = 9) and hyperthyroidism (n = 7) were evident. Thyroid microsomal and peroxidase antibodies were elevated in most of the patients, while thyroglobin antibodies were less frequently elevated. As AT without detectable thyroid antibodies can occur, a fine-needle aspiration cytology of the thyroid is important in nontypical cases. This type of cytologic examination should also be considered in patients with euthyroid nonendemic goiter, thyroid nodules and hyperthyroid goiter.

[Imaging and functional parameters in diagnosis of obstructive nephropathy]. / Bildgebende und funktionelle Parameter in der Diagnostik der obstruktiven Nephropathie.

Obstruction of the kidney leads to terminal kidney failure within a few years. Therefore, early recognition of such obstruction is of importance. Non-invasive diagnostic ultrasound examination now allows intrauterine visualization of a suspected obstruction. However, the implications of such a dilated ureteral pelvic system are obscure. Whether there is obstruction or dilatation can only be evaluated postnatally by a nuclear technique. The aim of our study was to measure the recovery of kidney function. We investigated 13 kidneys of 9 newborns or small infants (up to 2 years). The follow-up was continuous for up to 29 days. The parameters were: urine output (24-h clearance), glomerular filtration rate, fractional excretion of sodium and potassium, free water clearance, total protein excretion, albumin and alpha 1 microglobulin excretion. The urine output fell from 0.3 to 0.12 ml/min within 14 days after relief of obstruction. The glomerular filtration rate rose from nearly 30 ml/min to about 50 ml/min within a week. The fractional excretion of sodium and potassium indicated recovery of the proximal tubli. The fractional sodium excretion fell below 1% within 4 days. The free water clearance reflects the concentrating ability of the kidney, and in kidneys from newborns it had only positive values, while in kidneys of children older than 6 months there were also negative values. The protein excretion and the albuminuria showed recovery of the glomerular as well as the tubular system.(ABSTRACT TRUNCATED AT 250 WORDS)

[Extracorporeal shockwave lithotripsy in the treatment of pediatric urolithiasis]. / Extrakorporale Stosswellenlithotripsie in der Therapie der kindlichen Urolithiasis.

The 2nd generation lithotripter LITHOSTAR plus was used for extracorporeal shock wave lithotripsy of 9 kidney stones, 2 ureteral calculi and 2 bladder stones in 10 children 15 months to 17 years old. Ultrasonic stone localization was used in 2 children, x-ray guided stone localization in 8 children. General anesthesia was necessary in 6 children. A stone free rate of 60% was achieved after 1 treatment. Except for one 14-year old boy no adjuvant procedures like percutaneous nephrostomy or ureteral stents were applied. No major complications were encountered.

Choledochal cyst type I: successful endoscopic balloon dilatation of the distal common bile duct and sphincter of Oddi: a case report.

A 12-year-old boy with a choledochal cyst type I is reported with clinical features of abdominal pain, postprandial vomiting, weight loss and fatigue since 3 months. Diagnosis was made by ultrasound and confirmed by computer-assisted tomography (CAT) and endoscopic retrograde cholangiography (ERC). Instead of the usual surgical treatment balloon dilatation of the sphincter of Oddi and the distal common bile duct was performed by endoscopic means. The patient was relieved from his complaints, gained weight and felt healthy again. Sonographic and endoscopic reexamination had proven that the diameter of the common bile duct had diminished from 3,0 to 2,6 cm. Endoscopic balloon dilatation of choledochal cysts type I may be a valuable alternative to surgical treatment.

[Chronic neutropenia (author's transl)]. / Chronische Neutrozytopenie.

Chronic neutropenia was demonstrated in 6 members of a family including 3 children. Patient suffered from recurrent infections of the throat and upper respiratory tract and from lymphadenitis. There were no life-threatening diseases in any of the patients. In the bone marrow myelopoiesis showed arrested maturation. The previously reported forms of chronic neutropenia with mild clinical course are not differentiated either by haematological or by clinical data. We therefore suggest that they should be considered as one disease entity for the time being. This results in classification of childhood chronic neutropenia according to the clinical picture: a serious form (Kostmann) and cyclic neutropenia must be differentiated from the benign form described here.

[Significance of the antibacterial agent assay of urine for bacteriological diagnosis and control of chemotherapy of urinary tract infections (author's transl)]. / Bedeutung des Nachweises antibakterieller Stoffe im Urin für die bakteriologische Diagnostik und die Kontrolle der Chemotherapie von Harnweginfektionen

The disc agar-diffusion-test using Bacillus subtilis ATCC 6051 as test organism is a simple and rapid method for routine testing of antibacterial agents in urine specimens. The test records urine levels which are expected under medium dosage, and in many cases even lower concentrations of renal excreted antibiotics. Out of 5655 analysed urine samples 22% contain antibacterial substances. In urine specimens over which information was volunteered that either no chemotherapy had been administered or that more than a three day's interval free of therapy existed, inhibitory substances are found in 8% and 27% respectively. Urine specimens which are supposedly collected from patients under current chemotherapy do not show therapeutic relevant antibiotic levels in 26%. Between urine specimens with and without antibacterial activity there is no significant difference in the incidence of viable counts of 10-4-10-5/ml and 10-5/ml. From urine samples with antibacterial content increases in the numbers of multiple resistant strains of E. coli, Proteus spp., Pseudom. aerug. and Enterobacter spp. together with high numbers of Candida spp. are observed.