Quality of paediatric IDDM care in Germany: a multicentre analysis. German Paediatric Diabetology Group.

Quality management has been applied in recent years to improve the care of children and adolescents with insulin dependent diabetes mellitus (IDDM). In 1995 the German Paediatric Diabetology Working Group published standards on quality control, in which relevant parameters on structure, process and outcome of care were defined. A computer software programme-developed at the University of Ulm under the auspices of the German Secretary of Health-has been used for quality control with central anonymous analysis in a nationwide survey. Data from 23 paediatric centres with 2407 patients seen between January and June 1996 were evaluated. The results showed an admission rate to hospital of 23.8 per 100 patient-years with an average duration of in-patient stay of 2.74 days/year. 80% of the patients were treated with an intensive insulin therapy regimen comprising three or more injections daily. The overall metabolic control was reasonably good with a mean HbA1c value of 7.8%. The rate of severe hypoglycaemia complicated by coma and/or convulsions was six per 100 patient-years and of ketoacidosis one per 100 patient-years. Unfortunately screening for diabetic retinopathy and nephropathy was not carried out consistently. The incidence was 44% and 33% respectively.

Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes.

Because Wolfram (or DIDMOAD) syndrome is supposed to be a mitochondrial (mt)-mediated disease, we investigated a group of eight DIDMOAD patients with respect to point mutations of the mtDNA thus far described as being associated with defined mitochondrial disorders such as MELAS, MERRF, and LHON. Furthermore, to screen DIDMOAD patients for other mtDNA defects we used Southern blot analysis to detect mtDNA length mutations and rearrangements as well as PCR-SSCP and direct sequencing to screen all ND genes (complex I of the respiratory chain), the 22 tRNAs, and a part of the cyt b gene for unknown mutations. As a disease control group, 17 LHON patients (harboring one of the primary LHON mutations) were included in this study because of the overlapping clinical symptoms (optic atrophy) in both syndromes. We compared mtDNA variants identified in DIDMOAD patients with those found in LHON patients as well as in a control group consisting of 67 healthy German blood donors. In total, the control group was characterized by 29 polymorphic sites in ND and tRNA genes that define certain major Caucasian haplotypes. We found that a cluster of nucleotide exchanges at nucleotide positions (nps) 4216 and 11,251 roughly discriminates controls (12/67 controls, 18%) from the disease groups (6/8 DIDMOAD patients, 75%; 10/17 LHON patients, 59%). All 4216-positive LHON patients (10 patients) were concentrated in a haplogroup defined by additional exchanges at nps 10,398, 12,612, and 13,708 (haplogroup A), while the bulk of 4216-positive DIDMOAD patients (5 patients) were found in a distinct haplogroup consisting of nucleotide exchanges at nps 4917, 10,463, 13,368, 14,233, and 15,928. The frequencies of both haplogroups were significantly lower in the control group versus the respective disease groups. A more detailed analysis was performed by sequencing the two hypervariable regions of the non-coding D-loop region from patients and controls and corroborated the ranging in the two major haplogroups. Thus, the different clinical features of the mitochondrial disease groups investigated here corresponded to different clusters of mtDNA variants, which might act as predisposing haplotypes, increasing the risk for disease.

Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5 alpha-reductase deficiency.

UNLABELLED: Reduced conversion of testosterone (T) to dihydrotestosterone (DHT) results in defective virilization in karyotypic males. Different mutations in the 5 alpha-reductase type 2 gene cause the phenotypic variability of the disease. In this report we describe four prepubertal patients with a predominantly male phenotype who carry homozygous point mutations in the 5 alpha-reductase type 2 gene and address the specific T and DHT response to different human chorionic gonadotropin (hCG) stimulation tests. For molecular genetic analysis, DNA from peripheral blood leucocytes was studied. The coding region of the 5 alpha-reductase type 2 gene was characterized by exon-specific polymerase chain reaction amplification, non-radioactive single strand polymorphism analysis, and direct sequencing. Three different homozygous point mutations (Gly196-Ser, Arg227-Gln and Ala228-Thr) were identified in the patients. In contrast, in the DNA from 100 phenotypically normal males only two heterozygous abnormalities (Ile196-Ile, delta Met157) were characterized. For hormonal studies, T and DHT were measured in serum before and after hCG stimulation employing different protocols. HCG stimulation with 5000 IU/m2 once and prolonged stimulation with seven injections of 1500 IU hCG per single dose every other day were used. CONCLUSION: While abnormal T/DHT ratios were identified with both hCG protocols in the patients, prolonged stimulation lead to higher T values and to higher T/DHT rations, and hence to a better discrimination of pathologic results.

Lobar emphysema and atelectasis syndrome, a nosological unity.

Shrinking and atelectatic pulmonary processes--atelectasis syndrome--and lobar emphysema show morphological similarities: congenital malformations of the bronchial structure, external compression of the bronchi as well as inflammatory processes. Ventilation mechanics determine whether in the described processes an atelectasis or an emphysema manifests itself clinically. Usually, one finds over-expansions in connection with atelectasis syndrome and atelectases together with lobar emphysema. Both processes can be reversible, if we are not dealing with bronchial malformations. Longer lasting processes as well as acute, life threatening forms require operation. The belief that atelectasis syndrome and lobar emphysema constitute a nosological unity is illustrated by our cases of 9 patients with atelectasis syndrome and 16 patients with lobar emphysema.

Impaired glucose tolerance leads to delayed diagnosis of Alström syndrome.

OBJECTIVE: To emphasis the need for timely diagnosis of Alström syndrome. CASE: We report a case of late-detected Alström syndrome in a boy 15 1/2 years of age who was admitted because of poor wound healing and hyperglycemia. RESULTS: Diagnosis was made and the patient's impaired glucose tolerance improved by diet. CONCLUSIONS: Regular follow-ups are needed to recognize and possibly prevent late-appearing complications.

[Risk score and postoperative complications in pediatric surgery]. / Risikoscore und postoperative Komplikationen in der Kinderchirurgie.

We have developed a risk score meeting the special demands of pediatric surgery. It conveys an objective impression of the patients' preoperative condition and enables us to predict their individual intra- and postoperative behavior. This study compiles the course of 1425 operations carried out between 1986 and 1990. They were divided into low, intermediate and high risk. In addition, the patients were classified into six different age groups. We demonstrate that the number of points assigned by our risk score is highly correlated with the rate of complications that occurred, that accompanying malformations and diseases are correctly picked up and weighed by the score as far as their importance for the postoperative course is concerned, that the score is suitable for ascertaining which patients have a high probability of developing complications: the specificity is close to 100% for more than 12 points on the score, and the proportion of correctly predicted lethal courses (sensitivity) is also close to 100%. The significance of the risk score lies first in the possibility of giving patients exact data on the intra- and postoperative risk, and secondly in the provision of an objective measure of quality control--which is legally prescribed in Germany--and comparison with other hospitals. Third, the risk score gives clear starting points for research aiming at improvement in the field of surgery in sick children, and lastly it forms the basis for reliable preoperative recognition of high-risk as needed patients for modern payment methodology of the per-cose costs and thus makes it possible to charge accordingly.

Validation of dry heat inactivation of bacterial endotoxins.

Bacterial endotoxins (ETs) are lipopolysaccharides from the cell wall of Gram negative bacteria. ETs get into the environment as a result of autolytic desintegration of the bacterial cells. There exist a number of depyrogenation methods, either serving to remove or to inactivate ET. The most common means of ET inactivation is dry heat. Unfortunately no uniform regulation exists describing the conditions for sufficient ET inactivation. While the USP and FDA require an ET reduction of 3 log steps, no European regulation exists regarding depyrogenation of final containers for parenterals. However, the Ph. Eur. specifies the temperature and time conditions for depyrogenation of glassware in the pyrogen test monograph, allowing to choose between the two variants 250 degrees C/30 minutes or 200 degrees C/60 minutes which are not equivalent. In the present study those conditions for depyrogenation of glass containers in production of parenterals were investigated which, on the one hand, are technically feasible and, on the other hand, comply with the requirements of the main Pharmacopeias; furthermore, an ET preparation suitable for validation studies was selected. The preparation of ET indicators, the dry-heat inactivation and the recovery of ET are described in detail. Based on the results obtained, it is recommended to follow a defined treating temperature and period for safe depyrogenation of glass containers for parenterals, which results in a 4 log step reduction in ET without fillers. Thereby the USP/FDA requirement for a 3 log step reduction as well as the 200 degrees C/60 minutes requirement variant given in the Ph. Eur. can be fulfilled.

[Mortality and postoperative cause of death in pediatric surgery]. / Letalität und postoperative Todesursachen in der Kinderchirurgie.

We analysed our patients in pediatric surgery from 1959 to 1990 in regard to post-operative causes of death according to the Petren scheme. "Post-operative infection" as a cause of death dropped from 45% to 2%, "post-operative pneumonia" from 10% to 4%. Death due to accompanying congenital defects has increased from 3% to 15%. The cause of death "main disease" remained the same with 18%. Post-operative causes of death due to wrong diagnoses ranged at 2%, wrong treatment as cause of death decreased from 18% to 4%. In the 41 years' range of our survey, 115,598 children were operated as in-patients. During the first 5-year-period postoperative mortality was 2.2%, during the last 5-year-period 0.12%.

[Intersexuality and malignancy. Case report of an unreported association between a malignant disease in a child with androgen resistance syndrome in comparison with the most frequently expected malignant tumors in children with intersexuality]. / Intersexualität und Malignität. Kasuistik einer noch nicht beschriebenen Assoziation einer malignen Erkrankung bei einem Kind mit Androgenresistenz-Syndrom im Vergleich zu den am häufigsten zu erwartenden malignen Tumoren bei Kindern mit intersexuellem Genitale.

Patients with specific disorders in sexual differentiation have an increased risk for development of malignancies. The most frequent malignant tumors to be expected especially in childhood are gonadoblastoma (carcinoma-in-situ) by children with pure gonadal dysgenesis (Swyer-syndrome) with a calculated risk of approximately 30%. In this disorder the so called streak gonads have an age related, increased risk for development of malignancies. Furthermore, malignant tumors may be expected in children with mixed gonadal dysgenesis (in 10-20%), pure hermaphroditism (in the testes significantly higher than in the ovaries) and with androgen insensitivity syndrome. Risk values for the last are reported in the literature very differently. Rare disorders in this context are virilizing tumors of the adrenal cortex, the DRASH-syndrome (nephropathy, most male pseudohermaphroditism, Wilms-tumor) and similar disorders. Practical prophylactic and therapeutic procedures of the separate disorders respectively were discussed. We report about a child with androgen resistance syndrome and acute leukaemia. This would be to our knowledge the first description of such an unusual association of these two distinct disorders.

Thyroid carcinoma in childhood: management and follow up of 11 cases.

Eleven patients under 16 years of age, 5 males and 6 females were diagnosed with thyroid carcinoma in our hospital between 1974 and 1992. Median age at diagnosis was 9.5 years (range: 5.2-15.7 years). The presenting sign was a single thyroid nodule in 5, multiple thyroid nodules in 1, cervical adenopathy in 3, and thyroid nodules in conjunction with cervical adenopathy in 2 patients. Histological diagnosis was papillary carcinoma in 5 cases, follicular carcinoma in 2, mixed papillary-follicular carcinoma in 3, and anaplastic carcinoma in one. Only 4 patients had no extrathyroidal metastases at diagnosis. All but one subjects underwent total thyroidectomy, either one-stage or two-staged. If metastases were present, ablative radio-iodine therapy followed. Two patients died within a few months, one from complications of lung metastases, another from diffuse spread of anaplastic carcinoma. Two patients were lost to follow up; 7 patients have been followed for 9.0-18.0 years. Of these, one patient with initial lung metastases has had six recurrences which were successfully treated each time with radio-iodine although thyroglobulin levels remained elevated; another patient who had an initial subtotal thyroidectomy incurred a relapse 12 years later during pregnancy but is doing well now after more intensive surgery. We propose that children with differentiated thyroid carcinoma should undergo total thyroidectomy and selective lymph node extirpation by a skilled surgeon followed by whole body radio-iodine scan and ablative radio-iodine treatment if necessary. Plasma thyroglobulin can then be used as a tumour marker and suppressive levothyroxine does should be given.

New morphological findings in so-called negative appendectomies.

Appendices of children operated on because of clinical signs of acute appendicitis and presenting normal histological findings were revised by means of special assays. These findings were then compared with appendectomies during abdominal surgery, catarrhal and early phlegmonous appendicitis. We found pathological changes of the epithelium and the lymphatic tissue in more than two thirds of the specimens originally classified as normal. Therefore the term of "negative appendectomy" has to be redefined.

Clinical findings in middle lobe syndrome and other processes of pulmonary shrinkage in children (atelectasis syndrome).

Processes of atelectasis and pulmonary shrinkage are not confined to the right middle lobe. This fact is illustrated by case reports of five of our nine such patients. All cases shared common clinical and morphologic similarities: congenital malformations of the bronchial skeleton, compression, and chronic inflammation produce comparable pulmonary morphology that always includes atelectasis. Atelectasic processes of longer duration require surgical resection; this led to cures in all the authors' patients.

[The value of C-reative protein analysis for the differential diagnosis of non-acute appendicitis]. / Der Wert der CRP - Untersuchung in der Differentialdiagnose der nicht-akuten Appendizitis.

Appendicitis is one of the most common causes for laparatomy in children. Diagnosis can be very problematic, especially if appendicitis is combined with gastro-enteritis. Furthermore, difficulties can be encountered in diagnosis of diseases such as mucoviscidosis, leukosis, immunosuppressive or chemotherapy are present. In addition to the common clinical examination we have to look for other methods to complete the indication for appendectomy. Therefore in 1985 we added the CRP-determination to our diagnostics for patients with suspected appendicitis. In a retrospective study 269 patients who had signs of acute appendicitis were examined. We found that the determination of the CRP-level, in conjunction with the standard parameters of appendicitis, represents a valuable addition to the diagnostic armamentarium. However our data shows, that the CRP-level in itself cannot be regarded as a sole criteria for an unambiguous diagnosis of non-acute appendicitis, as it is the case with any other appendicitis parameter.