I. Sammelreferat. Frakturen,Verletzungen und traumatische Erkrankungen der Knochen

Ohne Zusammenfassung Ausser den Originalarbeiten wurden die Referate der Münchener med. Wochenschrift, des Centralblattes für Chirurgie und von Hildebrandts Jahresberichten benützt. (Fortsetzung und Schluss.)     

Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene.

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH in which the synthesis of all gonadal and adrenal cortical steroids is markedly impaired. We report here the clinical, endocrinological, and molecular analyses of two unrelated Japanese kindreds of 46,XX subjects affected with lipoid CAH who manifested spontaneous puberty. Phenotypic female infants with 46,XX karyotypes were diagnosed with lipoid CAH as newborns based on a clinical history of failure to thrive, hyperpigmentation, hyponatremia, hyperkalemia, and low basal values of serum cortisol and urinary 17-hydroxycorticosteroid and 17-ketosteroid. These patients responded to treatment with glucocorticoid and 9alpha-fludrocortisone. Spontaneous thelarche occurred in association with increased serum estradiol levels at the age of 10 and 11 yr, respectively. Pubic hair developed at the age of 12 yr 11 mo in one subject and menarche was at the age of 12 yr in both cases. Both subjects reported periodic menstrual bleeding and subsequently developed polycystic ovaries. To investigate the molecular basis of the steroidogenic lesion in these patients, the StAR gene was characterized by PCR and direct DNA sequence analyses. DNA sequence analysis revealed that one patient is homozygous for the Gln 258 Stop mutation in exon 7 and that the other patient is a compound heterozygote with the Gln 258 Stop mutation and a single A deletion at codon 238 in the other allele causing a frame-shift, which renders the StAR protein nonfunctional. These findings demonstrate that ovarian steroidogenesis can be spared to some extent through puberty when the StAR gene product is inactive. This is in marked contrast to the early onset of severe defects in testicular and adrenocortical steroidogenesis which are characteristics of this disease.     

Silent and multiple mutations in p53 and the question of the hypermutability of tumors [published erratum appears in Carcinogenesis 1998 Jan;19(1):237]

Published data on TP53 mutations can be used to examine the question of whether generalized hypermutability is a necessary condition for tumorigenesis. Although individual mutations do play an etiologic role in tumor formation, the evidence so far does not make it necessary to assume a general mutability. Silent and multiple mutations in the TP53 data set indicate that a special hypermutability process operates on this gene during the generation of tumors. The percentage of silent p53 mutations observed (3%) is at least 20 times greater than would be expected and indicates hypermutability for this gene. The greater proportion of silent mutations among multiple p53 mutations (10%) indicates that the mutations occur nonselectively. The presence of silent mutations implies that not all mutations observed in tumors have an etiologic role. Analysis of the distribution of tumors with two, three, four and more p53 mutations suggests that mutations in some tumors occur in clusters possibly as a result of 'stuttering' in DNA synthesis. It is argued that the most likely alternative explanations of the data, polymorphism and/or a selective role for silent mutations, are not correct. It remains possible that the hypermutability process is restricted to particular genes or to regions of the genome as, for example, in antibody production. There is a surprising paucity of data on human polymorphism and nucleotide diversity which makes the analysis difficult.      

The conventional versus the new radiological contrast media. Cost-benefit analysis and medicolegal implications

New iodinated radiological contrast media, which are safer but much more expensive than the conventional ones, have been introduced. Since the financial implications are considerable a compromise between cost and safety is inevitable. It is therefore recommended that, at present, the conventional media be used routinely and the new media be reserved for potentially painful examinations and for patients at higher risk. Should a question of wrongfulness or negligence concerning the use of contrast media be considered by our courts, they will undoubtedly be influenced by what is considered 'common practice' and 'accepted practice' within a medical specialty and that may be co-determined by socio-economic considerations.     

Psychological moods and subjectively perceived behavioral and somatic changes accompanying anabolic-androgenic steroid use.

To assess physiological and psychological states accompanying anabolic-androgenic steroid use, male weight lifters 1) were interviewed regarding their physical training and the patterns and effects of any drug use; 2) completed a written physical and medical history questionnaire, a Profile of Mood States questionnaire, and the Buss-Durkee Hostility Inventory; and 3) were physically examined, including a blood sample and urinalysis. Subjects were divided into current anabolic-androgenic steroid users (N = 12), previous users (N = 14), and nonusers (N = 24). Current and previous users reported the following changes associated with anabolic-androgenic steroid use: increases in enthusiasm, aggression, and irritability; changes in insomnia, muscle size, muscle strength and density; faster recovery from workouts and injuries; and changes in libido. We were unable to confirm these interview and physical and medical history questionnaire responses using standardized and well-accepted psychological inventories. There were no significant differences among groups for any Profile of Moods factor, total mood disturbance, total Buss-Durkee Hostility Inventory score, or any subscale. For current users, there were no significant correlations between either total weekly drug dose or length of time on the current cycle of anabolic-androgenic steroids and any individual scale of the Profile of Mood States, Buss-Durkee Hostility Inventory, Profile of Mood States total mood disturbance, or composite Buss-Durkee Hostility Inventory score. Furthermore, anabolic-androgenic steroid users did not differ in their responses on these inventories from nonusers or from general population norms.(ABSTRACT TRUNCATED AT 250 WORDS)     

The insulin-like growth factor, somatomedin-C, modulates low density lipoprotein metabolism by swine granulosa cells

Insulin-like growth factor I (IGF-I) synergistically amplified the stimulatory effect of low density lipoprotein (LDL) on progesterone biosynthesis by primary cultures of swine ovarian cells. The mechanisms subserving this facilitative interaction included the following. IGF-I's synergism with LDL was associated with a decrease in the mean half-maximally stimulatory concentration of LDL from 20-3.5 micrograms/ml. IGF-I increased by 3- to 6-fold the number of specific high affinity LDL receptors on ovarian cells, with no change in apparent binding affinity. IGF-I augmented by 3- and 18-fold the maximal rates of [125I]iodo-LDL internalization and degradation, respectively, without altering half-maximally effective concentrations of LDL supporting these processes. IGF-I increased by 2- to 2.5-fold the total mass of free and esterified cholesterol contained in granulosa cells. IGF-I stimulated the intracellular accumulation of free [3H]cholesterol and [3H]cholesteryl ester from exogenous [3H]cholesteryl linoleate-labeled LDL, and amplified [3H]progesterone secretion by granulosa cells exposed to this source of lipoprotein-borne sterol. These actions of IGF-I were demonstrated at 30- to 100-fold lower concentrations of IGF-I than insulin. We conclude that IGF-I and LDL synergistically enhance progesterone biosynthesis by ovarian cells. This synergism occurs in part via mechanisms that regulate the effectual delivery of lipoprotein-borne cholesterol substrate into cellular sterol pools that participate in steroid hormone biosynthesis.