Cystic fibrosis and neuroblastoma.

Two cases of coexistent cystic fibrosis and infantile thoracic neuroblastoma are presented. In one patient, neuroblastoma was congenital, and diagnosis of cystic fibrosis was made at 3 months of age; in the other, the diagnosis of cystic fibrosis was made at 7 months of age, preceding that of neuroblastoma by 4 months. In both infants, surgical resection of the tumors have been successful. Recent advances in the genetic aspects of neuroblastoma, including translocation and activation of the oncogene N-myc, are discussed. Current recombinant DNA technology, which can identify translocation of N-myc and allow localization of the cystic fibrosis gene if the translocation occurs near the cystic fibrosis allele, is being applied to these cases.

[Crohn disease in childhood]. / Morbus Crohn im Kindesalter.

Increasing incidence of Crohn's disease particularly in childhood and adolescence has made inflammatory bowel disease one of the most important aspects of paediatric gastroenterology. The multicenter paediatric Crohn's disease study group with members from F.R.G., Switzerland, and Austria diagnosed Crohn's disease in 527 patients by means of defined diagnostic criteria. With regard to epidemiology, genetics, aetiology, descriptive pathogenesis, anamnestical and diagnostical features and therapy the authors discuss their experience and results of the multicenter study group.

Remarks of a paediatrician on informed consent in children.

In medical practice, patients are frequently in a passive role with respect to consenting to medical measures. The basic threshold element of informed consent is medical competence to be controlled by individual self-criticism. The elements of information, such as disclosure and understanding, have to be adapted to the individual situation in order to achieve voluntariness and active autonomous authorization. In the paediatric age group, disclosure of information has to be guided by the age-dependent ability of understanding, leading to voluntariness and consent. Since force cannot be totally avoided in the management of children, parental information and consent should be as precise and conclusive as possible. The interaction between the paediatrician on the one hand, and the children and their parents on the other, is discussed.

[Therapy with H2 receptor antagonists in childhood. Use of ranitidine in duodenal and gastric ulcer and reflux esophagitis]. / Therapie mit H2-Rezeptor-Antagonisten im Kindesalter. Einsatz von Ranitidin bei Ulcus duodeni, ventriculi und Refluxösophagitis.

AIMS: Representation of common characteristics and peculiarities of the treatment with H2-receptor antagonists of duodenal and gastric ulcer and gastro-esophageal reflux in childhood in comparison with adults, taking ranitidine as an example. MAJOR POINTS: In the treatment of primary and chronic duodenal and gastric ulcers, ranitidine at doses of up to 10 mg/kg/day, given in two fractions (up to 300 mg daily) is a proven form of therapy. The endoscopically confirmed healing rates after 6 to 8 weeks of acute treatment vary between 80 and 100%. The recurrence rate in children with duodenal ulcer is high, so that long-term treatment with 4 to 5 mg/kg/day (evening dose) is added. Following a recurrent ulcer, treatment should be continued for one to two years. Ranitidine has been used with success for the treatment of gastroesophageal reflux. Shorter intervals between administrations (3 times a day) with a total dose of up to 10 mg/kg/day are to be recommended. More experience is required in this area. At therapeutic doses, ranitidine shows hardly any side effects in children, even with long-term treatment, and can be considered to be very well tolerated by this age group, including babies.

Intestinal obstruction in Crohn's disease in childhood.

Out of 540 children and adolescents from the Multicenter Pediatric Crohn's Disease Study Group, 42 patients presented with decompensated intestinal obstruction. In 26 patients only one intestinal obstruction occurred, and in 16 children up to five intestinal obstructions occurred. Conservative measures were successful in 37 of 72 episodes of intestinal obstruction (51.4%), while 19 of 42 patients underwent emergency surgery (45.2%) and 16 of 42 (38.1%) were operated on following conservative treatment. From analysis of clinical, intraoperative, and histological findings in surgically treated patients, criteria for emergency surgery and elective surgery of intestinal obstruction in Crohn's disease are derived. One patient with adenocarcinoma of the large bowel, presenting with recurrent obstruction, signals caution in delaying proper diagnosis.

Anion transport and 2,3-diphosphoglycerate in cystic fibrosis red blood cells.

The monovalent and divalent anion transport in red blood cells from patients with cystic fibrosis and controls is not significantly different. The protein pattern of the erythrocyte membrane, as seen by sodium dodecyl sulfate-polyacrylamide gel electropherograms, is similar in cystic fibrosis and control red blood cells. The 2,3-diphosphoglycerate content of the investigated cystic fibrosis red blood cells is normal.

Crohn's disease in cystic fibrosis.

We report on three patients suffering from cystic fibrosis (CF) who developed gastrointestinal symptoms of Crohn's disease (CD). Two patients developed enteroenteric or enterocutaneous fistulas. The diagnosis of CD is based on typical endoscopic, radiologic, and histological features of epithelioid granulomas in two children.

[Infection due to Yersinia enterocolitica in healthy and chronically ill children (author's transl)]. / Septische Verlaufsformen von Yersinia-enterocolitica-Infektionen bei gesunden und chronisch kranken Kindern.

A septicaemic course of infection due to Yersinia enterocolitica developed in three children, two Italian girls with thalassemia (serotype 03) and a previously healthy boy (serotype 09). There were marked gastrointestinal symptoms. The boy required two transfusions for acute haemolysis. Because it may take a serious course, the possibility of this organism as the causative agent should be considered in the differential diagnosis of severe infections, especially in patients with chronic debilitating disease. The death rate is about 30%.

Alpha-1-antitrypsin deficiency: fulminant course in early infancy.

A severe course of alpha-1-antitrypsin deficiency in two children with Pi ZZ genotype is demonstrated. Clinically both infants presented with signs indistinguishable from biliary atresia with acholic stools and a low I131-rose bengal excretion over 72 h. Rapid development of liver fibrosis documented by serial liver biopsies, indicated a bad prognosis. The infants died at the age of 6 and 15 months. The extent of fibrosis is estimated to be the most useful prognostic sign in prediction of the probable outcome in alpha-1-antitrypsin deficiency.

[Abetalipoproteinemia (author's transl)]. / Abetalipoproteinämie.

A 21/2-years-old Greek girl with marked failure to thrive and steatorrhea diagnoses to suffer from abetalipoproteinemia by the dissecting microscope appearance of a white intestinal mucosa. This specific finding is due to storage of lipids in the enterocytes. Another typical finding is the acanthocytosis in blood smears. Serum lipids were studied in detail in the patient and her relatives; there was a marked reduction of the low and very low density lipoproteins in the patient only (LDL/VLDL). The most characteristic finding is the lack of apolipoprotein B.

Ciprofloxacin pharmacokinetics in patients with cystic fibrosis.

The pharmacokinetics of ciprofloxacin were studied in cystic fibrosis patients and healthy volunteers following oral administration of 500 mg and 1000 mg. Serum kinetics as well as urinary recovery were monitored. As the body weights of cystic fibrosis patients and the healthy volunteers differed significantly, kinetic parameters were calculated on the basis of a constant relative dose in mg/kg body weight. Neither serum kinetics nor urinary recovery differed significantly between the two groups, as indicated by the serum concentration versus time curves ranging from 1.1 to 1.4 mg X h/l, the elimination half-life of 4.4 to 5.1 h and the 24 h urinary recovery which amounted to 35% to 41% of the dose administered. Serum concentrations were linearly proportional to the doses administered. Sputum concentrations were monitored in cystic fibrosis patients. Again, ciprofloxacin sputum levels were linearly proportional to the doses and were within the same range as serum concentrations. Thus, ciprofloxacin kinetics are not altered in cystic fibrosis patients as compared to healthy volunteers.

Severe hemorrhage from intestinal hemangiomatosis in Klippel-Trenaunay syndrome: pitfalls in diagnosis and management.

A child with Klippel-Trenaunay syndrome (KTS) and severe anemia caused by bleeding from diffuse intestinal hemangiomatosis is presented. Hemangiomas of the bowel should be considered in any child with unexplained anemia and coexisting cutaneous hemangiomas. The diagnostic workup of patients with KTS and symptomatic hemangiomatosis is outlined with respect to indications for surgical management.

A double-blind placebo controlled trial with oral ambroxol and N-acetylcysteine for mucolytic treatment in cystic fibrosis.

The therapeutic efficacy of oral N-acetylcysteine (NAC) and ambroxol as compared with the effect of placebos was studied in 36 cystic fibrosis (CF) patients with mild to moderate pulmonary disease. The patients were randomly assigned to one of three regimens, matched on the basis of age and Chrispin-Norman scores. The trial was conducted over a period of 12 weeks. Patients were assessed clinically and by extensive pulmonary function techniques (body-plethysmography, maximal expiratory flow-volume curves, trapped air determination). Although no clinical differences could be observed between the three groups, significant impairment in the placebo group was found for trapped air and FEV1 when compared to the active groups, suggesting a therapeutic effect of ambroxol and NAC in CF.

[Familial occurrence of Peutz-Jeghers syndrome and Crohn disease with manifestation of both diseases in the same patient]. / Familiäres Vorkommen von Peutz-Jeghers-Syndrom und Morbus Crohn mit Manifestation beider Erkrankungen beim gleichen Patienten.

This is the first communication on a coincidental manifestation of Peutz-Jeghers syndrome and Crohn's disease. In the index case polyposis was found at the age of eight and Crohn's disease was diagnosed at the age of 121/2 years. In this family, both the father and the eldest sister of the patient have a Peutz-Jeghers syndrome. The cousin of the mother also has Crohn's disease. The prognosis of a combination of these two diseases can be considered poor. The differentialdiagnosis posed difficulties.

Crohn's disease activity: assessment by factor VIII coagulation proteins.

Twenty-eight patients (mean age 13.5 years) with proven Crohn's disease were examined for factor VIII coagulation activity (VIII:C), factor VIII-related antigen (VIII R:Ag), and factor VIII-related ristocetin cofactor activity (VIII R:RCF). The factor VIII coagulation proteins were correlated with disease activity index according to van Hees and were compared with inflammatory parameters such as erythrocyte sedimentation rate, c-reactive protein, and orosomucoid. Among the factor VIII proteins, factor VIII-related protein (VIII R:Ag) correlates best with van Hees disease activity index, orosomucoid, c-reactive protein, and erythrocyte sedimentation rate (p less than 0.001 for all parameters). Since acute phase proteins are produced by liver cells, whereas VIII R:Ag is synthesized by endothelial cells, we postulate that this coagulation factor is highly sensitive in reflecting the inflammatory process in the intestine.

[Prevalence of gallstones in the neonatal period]. / Prävalenz von Gallensteinen in der Neugeborenenperiode.

AIM: To assess the prevalence of gallstones in normal neonates. METHOD: We used sonography to assess the gallbladder in 3500 unselected infants between 1993 and 1995. Examination was performed during the first four days of life as part of a prospective neonatal screening study evaluating hip and renal abnormalities. RESULTS: We found sludge or gallstones in 19 children (0.5%). In 4 of 11 patients followed for up to 18 months, the gallstones persisted. In 3 of the cases, there was a family history of gallstones. None of the children had signs of cholestasis. Three were treated with ursodesoxycholic acid 15-20 mg/kg (per day): only one responded. CONCLUSION: About 0.5% of neonates have gallstones or gall bladder sludge; this is a higher percentage than previously thought. In one-third of the patients who were followed, the gallstones remained. Persistence was more likely in those with a positive family history for gallstones.

HLA antigen frequencies in familial Crohn's disease (CD).

A possible association of Crohn's disease (CD) with MHC (major histocompatibility complex) markers was investigated in families with more than one affected member. HLA-A, B, C, DR and DQ typing was performed in 21 CD families with two or more CD patients. The following HLA-antigens showed increased relative risk (RR) values for CD: B44 (RR = 2.43; B15 (Bw62, Bw63) (RR = 2.03); DR7 (RR = 1.85); DR4 (RR = 1.06). Three of 44 patients were DR4- and four DR7-homozygous. The risk haplotype B44/DR7 was observed in four and Bw62/DR4 in three CD patients, respectively. CD affected family members (female greater than male) shared HLA haplotypes more frequently than expected by mendelian laws. None of the differences reached statistical significance.

[Spontaneous pneumothorax in cystic fibrosis]. / Spontanpneumothorax bei Cystischer Fibrose.

The clinical course of 13 cystic fibrosis patients with a total of 24 episodes of pneumothorax was analysed. The study is based on 488 (273/215) patients seen over 20 respectively 10 years at the University Children's Hospitals Frankfurt/Main and Essen. A pneumothorax was observed with a frequency of 2.7% mainly in adolescents of young adults with advanced pulmonary disease (mean age 17.4 years). It was not seen before the age of 10 years. Thus among 255 patients at risk above 10 years a pneumothorax occurred in 5.1%. Presenting symptoms were acute chest pain (n = 17), dyspnea (n = 17) and irritating cough (n = 8). In two patients pneumothorax was an incidental diagnosis. A tension pneumothorax was seen in 7 (= 30%; 3 initial, 4 recurrences of which 3 were ipsilateral). Out of 11 recurrences (n = 6, ipsi- and n = 5, contralateral) 4 occurred only once, one twice and in one patient five times. Two patients died as a consequence of the event (one initially due to tension pneumothorax, one due to heart failure). The therapeutic approach was conservative. Without specific treatment pneumothorax resolved in 12 cases. Ten patients were treated by chest tube drainage and only one patient by pleurodesis with a sclerosing agent. Though the therapeutic results were favorable in the patients presented, the authors suggest more aggressive treatment in view of the high ipsilateral recurrence rate. Detailed recommendations are given.

Primary intestinal enteropeptidase deficiency.

A rare case of primary enteropeptidase deficiency is reported. Details are given of the initial clinical presentation, treatment, and response of the patient from birth to the age of 18 months. Biochemical analysis of a small intestinal biopsy and duodenal juice samples confirmed the total absence of enteropeptidase activity. Proteolytic activity was very low in native duodenal juice, but normal levels could be induced by activation in vitro with a small amount of porcine enteropeptidase.