Prevalence, concordance, and heritability of Scheuermann kyphosis based on a study of twins

BACKGROUND: The purpose of this study was to establish a cohort of symptomatic twins with Scheuermann kyphosis to provide estimates of prevalence, concordance, odds ratio, and heritability. These estimates indicate to what extent genetic factors contribute to the etiology of this disease. METHODS: The Odense-based Danish Twin Registry is unique in that it contains data on all 73,000 twin pairs born in Denmark over the last 130 years. For the present study, all 46,418 twins born from 1931 through 1982 received a seventeen-page questionnaire, in which one question was "Have you been diagnosed with Scheuermann disease by a doctor"? The prevalence of self-reported Scheuermann disease was calculated, with the total number of answers used as the general population. Pairwise and probandwise concordance, odds ratio, tetrachoric correlations, and heritability were calculated. RESULTS: We found that the overall prevalence of Scheuermann disease was 2.8%, with a prevalence of 2.1% among women and 3.6% among men (p < 0.0001). The pairwise concordance for monozygotic twins was 0.19 compared with 0.07 for dizygotic twins. The probandwise concordance was 0.31 for monozygotic twins and 0.13 for dizygotic twins. The odds ratios were 32.92 and 6.25 in the monozygotic and dizygotic twins, respectively. These differences were significant (p < 0.01). Heritability was 74%. CONCLUSIONS: In a large cohort of twins that included almost 35,000 individuals, the self-reported overall prevalence of Scheuermann disease was 2.8% and the male-to-female ratio was close to 2:1. Because the pairwise and probandwise concordance and the odds ratio were two to three times higher in monozygotic than in dizygotic twins and the heritability was high, we concluded that there is a major genetic contribution to the etiology of Scheuermann disease.     

Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study

PURPOSE: VNP40101M (Cloretazine), a novel DNA alkylating agent, was evaluated in a phase I study in children with recurrent brain tumors. EXPERIMENTAL DESIGN: VNP40101M was given i.v. daily for 5 consecutive days every 6 weeks for up to eight cycles. Dose escalation was done independently in patients stratified based on intensity of prior therapy (moderately pretreated, stratum I; heavily pretreated, stratum II). Correlative studies included pharmacokinetics and measurement of O(6)-alkylguanine-DNA alkyl transferase levels in peripheral blood mononuclear cells before and after treatment. RESULTS: Forty-one eligible patients (stratum I, 19; stratum II, 22) were enrolled on this study. The dose-limiting toxicity in 35 evaluable patients was myelosuppression, which occurred in 4 of 16 patients in stratum I and 3 of 19 patients in stratum II. Pharmacokinetic studies showed a median terminal half-life of 30 min (range, 14-39.5). The maximum tolerated dose in stratum I and II were 45 and 30 mg/m(2)/d daily for 5 days every 6 weeks, respectively. Peripheral blood mononuclear cells alkylguanine alkyl transferase levels did not decrease significantly after VNP40101M treatment. Central imaging review confirmed that three patients had stable disease for a median of 45 weeks (range, 37-61+) after therapy. CONCLUSIONS: The recommended dose of VNP40101M for phase II studies in children with brain tumors is 45 mg/m(2)/d in moderately pretreated and 30 mg/m(2)/d in heavily pretreated patients when administered for 5 consecutive days every 6 weeks.     

Serum Concentrations of Immunoglobulins and Free Light Chains before and after Vascular Events in Essential Hypertension

Serum concentrations of immunoglobulins (Ig) and free light chains (LC) of Ig have been determined at regular intervals during five years in patients with essential hypertension and correlated to development of vascular complications. In 6 cardiac event patients serum IgG increased by 11.9% (p<0.05) and LC by 19.8% (p<0.05). IgG levels correlated positively with LC levels (r= 0.59, p<0.001) and changes in IgG correlated positively with changes in LC (r=0.46, p<0.01). The post-event increments in IgG persisted up to 21 months. No significant changes in serum concentrations of Ig A, IgM, albumin and creatinine were found. In 10 cerebral event patients and in matched groups of 15 uncomplicated hypertensive patients, no significant changes in the above parameters could be demonstrated. It is concluded that heart tissue damage in essential hypertension induces a long-lasting stimulation of B-lymphocytes, and it is suggested that the high Ig levels found in as yet uncomplicated hypertensive patients may reflect an ongoing damage of the vascular bed.     

Evidence for high affinity prostacyclin binding sites in vascular tissue: radioligand studies with a chemically stable analogue

Prostacyclin-specific binding sites are described in the muscularis of pig aorta using [3H]ZK 36374, a chemically stable prostacyclin analogue, as radioligand. Under standard incubation conditions [300 micrograms membrane protein in 350 microliter Tris buffer (50 mmoles/l., pH 7.4) containing 3 mM Ca2+ at 37 degrees for 10 min] both association and dissociation were complete within 30 sec, thus not allowing the determination of association or dissociation rate constants. The Scatchard plot was upward convex, whereas the Hill plot was linear, having a slope of 1.9. The equilibrium dissociation constant (KD) was 22.4 nmoles/l. and the specific binding was saturated at 360 fmoles [3H]ZK 36374/mg protein. The reversibility of binding was demonstrated by displacement of bound ligand with ZK 36374, its 5-(Z)-stereoisomer (ZK 36375), PGI2 and PGE1, but not with PGF2 alpha. The data suggest high affinity binding sites for ZK 36374 in the smooth muscle cells of pig aorta for which PGI2 may be the physiological ligand. They also demonstrate a possible co-operativity with two molecules binding simultaneously to two interacting sites.     

Die Bedeutung des Blutgehaltes der Netz- und Aderhaut für die Lähmungszeit des Elektroretinogramms beim Kaninchen

Zusammenfassung Beim Kaninchen wird die Lähmungszeit des Elektroretinogramms nach intraocularer Druckerhöhung und nach Stickstoffbeatmung bestimmt. Die Versuche ergeben, daß die Lähmungszeit nicht nur von der Ischämie und Anoxie, sondern auch vom Blutzuckerspiegel und der Belichtungsfolge abhängig ist. So wird die Lähmungszeit durch Hyperglykämie verlängert und durch Hypoglykämie verkürzt. Im Vergleich zur Einzelbelichtung wird sie durch intermittierende Lichtreize reduziert.Für den Unterschied der Lähmungszeit nach intraocularer Druckerhöhung und Stickstoffbeatmung wird der verschieden große Blutgehalt der Netz- und Aderhaut beider Versuche angesehen. Hierbei besitzt die Aderhaut durch ihren Gefäßreichtum den prozentual größten Vorrat an energieliefernden Substanzen, während die Energiereserven des Gewebes nur eine untergeordnete Rolle spielen dürften. Sie werden im wesentlichen gebildet durch die Nährfunktion des Blutes (Glucose) und in geringem Maße durch die im Gewebe liegenden Erythrocyten. Der Energieumsatz wird außerdem von der Reizfolge beeinflußt, wofür die Differenz der Lähmungszeit bei Einzel- und intermittierender Belichtung spricht.Mit 5 TextabbildungenDurchgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.