The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Bone mineral density and bone metabolism in patients with major depressive disorder without somatic comorbidities.

BACKGROUND: Major depressive disorder (MDD) has been linked with accelerated bone loss leading to the development of low bone mineral density (BMD). Several mechanisms have been discussed as causative factors, e.g. lifestyle, selective serotonin reuptake inhibitor (SSRI) intake, or the influence of proinflammatory cytokines. METHODS: In a cross-sectional study of in-patients with a current episode of MDD, without somatic comorbidities, we determined various parameters of bone metabolism, inflammatory parameters and parameters of depression. BMD was measured by dual x-ray absorptiometry. RESULTS: Of 50 patients, only one had low BMD in any of the measure sites. Body mass index (BMI) correlated positively with Z-scores. 83.3% of the examined patients had elevated osteoprotegerin (OPG) levels. SSRI intake did not have an effect on BMD. BMD in the femoral neck was significantly lower in smokers. We also found a positive correlation between the level of physical activity and osteocalcin levels. CONCLUSIONS: In our sample, young to middle-aged, somatically healthy, and acutely depressed patients with a history of MDD showed no reduction of BMD. This could be due to compensatory mechanisms, as suggested by elevated OPG levels. Physical activity and high BMI could also have served as protective factors. Still, as patients with MDD often suffer from comorbidities or take medication with a negative effect on bone, this population should be appreciated as a high-risk group for the development of osteopenia and osteoporosis.

[Hormonally active pancreatic tumors (apudomas). A review]. / Hormonal aktive Pankreastumoren (Apudome). Eine Ubersicht.

Hormonally active pancreas tumours have ceased to be rare cases, and by means of up-to-date methods they are now more frequently diagnosed than they used to be in the past. An account, based on the authors' own experience, is given in this paper of diagnostic and surgical problems relating to the various hormone-producing tumours of the pancreas. Particular reference is made to the treatment of malignant apudomata and to new concepts which have resulted from the introduction of H2 receptor blockers.

[Peptide hormones and the "new endocrinology"]. / Peptidhormone und "Neue Endokrinologie".

On the basis of the results found in literature a survey is given of the state of the peptide-chemical research from the point of view of the clinic. The functional mechanisms of the peptide hormones are explained, their effect as hormone and neurotransmitter is demonstrated. Particularly emphasized are the integrative tasks of the peptide hormones, which thus as another regulation principle of the organism are to be put by the side of the nervous and hormonal regulation. By the demonstration of the most frequent endocrine tumour syndromes with formation of adequate hormones the clinical importance of these substances is dealt with. The infrequency of these diseases is emphasized by the small number of own observations. It is referred to the growing importance of the peptide hormones in the diagnostics and therapy of internal and surgical diseases.

Brachydactyly in a child with duplication-deficiency subsequent to t(15;20)(q25.2;p12.2)mat. Candidate regions on one or both chromosomes?

We report a child with a duplication-deficiency subsequent to t(15;20)(q25.2;p12.2), transmitted in at least 5 generations, who showed features of 15q- syndrome. We speculate that brachydactyly--most likely because of brachymesophalangism--is a feature of the phenotype of this chromosomal aberration and points to candidate gene(s) in this region. A similar brachydactyly was, however, reported with dup(20p1-pter).

Successful systemic low-dose lysis of a caval thrombus by rt-PA in a neonate with congenital nephrotic syndrome.

PURPOSE: Thrombotic complications in nephrotic syndrome due to renal loss of antithrombin III (AT III) are well known. With this case report, we want to demonstrate the possibility of achieving the lysis of such a thrombosis in the neonatal period with low-dose rt-PA. PATIENTS AND METHODS: We treated a 10-day-old newborn who had congenital nephrotic syndrome, who developed a caval thrombosis during the first days of his life. After a trial of heparin (up to 20 IU/kg/hour) over a period of 24 hours and treatment with AT III (2 x 250 IU/day) proved to be ineffective, we started systemic thrombolytic therapy with rt-PA. An initial bolus of 0.4 mg/kg during 1 hour was followed by an infusion of 0.5 mg/kg/d rt-PA over a period of 36 hours. Low-dose heparin (5 IU/kg/hour) was given simultaneously. Complete clot dissolution could be achieved this way. No adverse effects were observed, including no clinical signs of bleeding. CONCLUSION: It seems that low-dose rt-PA treatment is safe and effective in dissoluting large caval thromboses in neonates.

Prognosis of children born to mothers with HELLP-syndrome.

In literature there have been differences in the assessment of the outcome of children born to mothers with HELLP syndrome. In a retrospective study we investigated six annual groups (1989-1994) at the Perinatal Center in Erlangen (11,235 births, 68 children of mothers with HELLP syndrome), 53 children were treated in our neonatal intensive care unit (NICU). The control group (n = 219) consisted of a complete age group in our NICU. The gestational age (mean 33 weeks, p < 0.003) and the birth weight (mean 1671 g, p < 0.001) were significantly lower in the HELLP group. No significant differences were detected with respect to the frequency of leucocytopenia (p = 0.518) and thrombocytopenia (p = 0.215). Despite a relatively high rate (37.7%) of RDS there was only a significant tendency to the disadvantage of HELLP children (p = 0.075). There was no difference in frequency of intracranial hemorrhage (ICH) (p = 0.566). Infections were diagnosed less frequently in HELLP children (p = 0.042). Mortality in the control group was higher only as a tendency (p = 0.07). The follow-up examinations of the neurological development covered 31 of the 53 treated children. After 6-72 months (median 24 months), 90.3% of these children showed normal development or only minor disabilities. The prognosis of children of mothers with HELLP syndrome is not as bad as has been assumed so far.

Differences in molecular heterogeneity of glucagon-like immunoreactivity in plasma and liver metastases of a patient with alpha-cell tumor.

In the present study we characterized and compared the different molecular forms of glucagon-like immunoreactivity in extracts of peripheral plasma and hepatic metastases of a patient with pancreatic alpha-cell tumor. Plasma and tissue extracts were chromatographed on Sephadex G-50 columns. Immunoreactivity in the eluting fractions was assayed with an anti-glucagon antiserum that specifically recognizes the C-terminal region of the pancreas glucagon molecule. Total plasma glucagon-like immunoreactivity prior to surgery was 26.64 nmol/l and consisted of four peaks of immunoreactivity of apparent 9,000 mol wt, 5,800-5,400 mol wt, and 4,000 mol wt. Total glucagon-like immunoreactivity extracted from the hepatic metastasis was 47.41 nmol/g wet weight and eluted as two major peaks of immunoreactivity as follows: peak I, mol wt 3,800, corresponding to "true" 3,500 mol wt glucagon; peak II, mol wt 1,400, probably consisted of glucagon degradation products. The results clearly demonstrated that both plasma and glucagon-like immunoreactivity extracted from hepatic metastases were heterogeneous and comprised species corresponding not only to "true" glucagon but also to higher mol wt forms. The lack of higher mol wt forms of immunoreactivity in the hepatic metastases of the alpha-cell tumor suggests that this metastatic tumor tissue may contain an enzyme capable of converting the higher mol wt forms to smaller glucagon-like components whereas this degradative system seems to be defective in the primary tumor.

[Calcitriol administration during pregnancy in a partial DiGeorge anomaly]. / Calcitriol-Gabe in der Schwangerschaft bei partieller DiGeorge-Anomalie.

A 23-year-old pregnant woman was known since birth to have partial DiGeorge syndrome with idiopathic hypoparathyroidism and clinically suspected thymus hypoplasia. The hypocalcaemia had until recently been treated with 1000 IU vitamin D3 daily. During the 9th week of pregnancy the serum calcium level was 1.9 mmol/l, the phosphate one 1.58 mmol/l and parathormone 5.6 pg/ml. To ensure better control, calcitriol was given (1.25-[OH]2-vitamin D3, initially 1 microgram daily and then, from the 22nd week of pregnancy onward, 1.5 micrograms daily), as well as calcium gluconate and lactate (initially 300 mg daily, then 900 mg daily). The serum calcium level at that time was between 2.0 and 2.5 mmol/l. Because of toxaemia of pregnancy the patient was hospitalized and confined to bed during the 37th week, whereupon the serum calcium level rose from 2.2 to 2.7 mmol/l, but a decrease in calcitriol dosage resulted in a decrease to within normal limits within one day. A girl was delivered by section in the 39th week: she had normal serum calcium and phosphate levels and appeared healthy.

Pharmacokinetic and clinical evaluation of serious infections in premature and newborn infants under therapy with imipenem/cilastatin.

Efficacy and pharmacokinetic parameters of imipenem/cilastatin (I/C) were investigated in a retrospective evaluation in 104 premature and newborn infants. Patients enrolled in this investigation constituted a particularly high risk group with extreme prematurity, perinatal asphyxia and amnion infection as well as various malformations. In 15 of the 104 infants serum concentrations were measured for drug monitoring and determination of optimal total daily dosage. A total daily dose of 50 mg/kg birth weight for premature and newborn infants divided into two doses led to imipenem peak concentrations of 17.7 mg/l +/- 9.2 mg/l (range: 1.95-38.05) and trough levels were 2.35 mg/l +/-1.02 (range 2.34-10.88) in premature infants. Imipenem peak concentrations of 20.6 +/- 10.8 (range 3.94-32.3) and trough levels of 0.43 +/- 0.17 (range 0.16-0.94) were measured in newborns. The half-life of elimination was 3.3 h and 1.86 h, respectively. Six of the 104 treated patients died, five of them of causes unrelated to infection. Seizures occurred in 8.9% of patients during therapy with I/C compared with 5.8% of a large survey of premature and newborn infants in our intensive care unit (ICU). However, the severity of illness of these two groups cannot be compared. I/C can be expected to constitute effective therapy in premature and newborn infants with serious nosocomial infections even after failure of other broad spectrum antibiotics.