Clinical phenotype and molecular diagnosis of multiple epiphyseal dysplasia with relative hip sparing during childhood (EDM2).

We report on a family of 19 individuals over four generations in which 12 members are affected with a variant of multiple epiphyseal dysplasia. Beginning in childhood, the disease leads to pain and stiffness of knees, ankles, elbows and finger joints. Some adult patients repeatedly suffer from free articular bodies resulting in locking of the joint. Finally, affected individuals are prone to the development of early degenerative joint disease. Mutation screening of candidate regions revealed a novel point mutation at position -1 in the COL9A2 exon 3/intron 3 splicing region. This G --> C substitution most probably induces an alteration of the splicing process. Family screening was carried out by both automated sequencing and by digestion of amplicons with BsaWI. We confirmed the nucleotide substitution in eight clinically affected family members as well as in three presymptomatic young children. Electron microscopy showed that the diameter of collagen fibrils from arthroscopically removed free articular bodies of two patients was not obviously different from that of normal articular cartilage. Together with previous reports our results indicate that mutations leading to skipping of exon 3 within the COL3 domain of the alpha2-chain of collagen type IX may be relatively common in patients with a special subtype of multiple epiphyseal dysplasia (MED) in which the hips are not markedly affected at early age (EDM2). In these patients and their families, mutation screening of the candidate regions may help to confirm the diagnosis, lead to appropriate advice for lifestyle and well based genetic counseling.

[Ambulatory diagnosis and therapy of gonarthrosis]. / Ambulante Diagnostik und Therapie der Gonarthrose.

AIM OF STUDY: To develop recommendations for appropriate diagnostic procedures and conservative treatment of knee osteoarthritis in outpatients. MATERIAL AND METHODS: Following a consensus conference and expert reviews basic recommendations were developed. RESULTS: While standardized radiographic assessment is mandatory, MRI investigation should be restricted to problems apart from osteoarthritis. Indications for physical therapy, bracing and pharmaco-treatment depend on the severity of the disease. Guidelines for intraarticular injections are presented. CONCLUSION: Effective treatment of knee osteoarthritis must be based on available recommendations and guidelines.

[Gerontologic aspects of postmenopausal measurement of bone density and prevention of osteoporosis]. / Gerontologische Aspekte bei postmenopausaler Knochendichtemessung und Osteoporoseprophylaxe.

I. Among 454 postmenopausal women to undergo bone mineral density (BMD) examination 7 out of 10 were aged 50 to 70 years. 1. 50 of patients older than 70 years had BMD examination because of being clinically suspicious of osteoporosis. 2. In this group of age 4 out of 10 women had BMD results of the lumbar spine below 0,8 gcm2. 3. Half of all women aged up to 50 years had a positive family history of osteoporosis. 4. Patients older than 60 years often underestimated their own risk of osteoporosis. 5. 50 of women up to the age of 50 and only one sixth of women older than 70 said they had very good to good knowledge of osteoporosis. 6. Resentments against estrogen substitution are rapidly growing with every decade of age. 7. Only one third of the women selected by BMD-indication were ready to accept longterm estrogen substitution to prevent osteoporosis. II. 4 out of 10 women had entered menopause maximally 8 years ago.1. Out of this group 6 of 10 patients were substituted with estrogen. 2. When menstruation had sisted more than 15 years ago the BMD examination indication, clinically suspicious of osteoporosis, rose immensely and made up for 50 of patients. 3. One third to one half of patients who had reached menopause more than 22 years ago showed pathological BMD results, which means they were at risk of fractures. 4. In this group only 1 in 10 women had a positive history of osteoporosis. III. Obese postmenopausal women (more than 25 of overweight according to Broca) had pathologic BMD results only half as often as postmenopausal women with normal weight. Summing it up these facts may be the basis of special counselling on the prevention of osteoporosis by estrogen substitution.

[Echocardiographic studies in children with chronic kidney insufficiency and intermittent hemodialysis treatment]. / Echokardiographische Untersuchungen bei Kindern mit chronischer Niereninsuffizienz und intermittierender Hämodialysebehandlung.

Cardiac function was measured in 10 children (mean age 12 years) undergoing chronic intermittent hemodialysis. Blood pressure, heart rate and body weight were checked three times before and after hemodialysis. Echocardiographic studies were performed according to the references of the American society of echocardiography. 6 patients were normotensive, 4 patients hypertensive. Cardiac function was normal before and after hemodialysis in all patients. Ultrafiltration reduced body weight on average by 1.2 kg. The mean systolic blood pressure remained unchanged, the mean diastolic blood pressure declined in normotensive patients from 66 mm Hg to 53 mm Hg and in hypertensive patients from 100 to 85 mm Hg on average; the systolic leftventricular diameter (LVES) was reduced by dialysis from 2.7 to 2.3 cm, the enddiastolic leftventricular diameter (LVED) from 4.42 to 4.02. Cardiac output declined from 62.04 ml to 56.68 ml/min, whereas heart rate, shortening fraction and mean circumferential fiber-shortening-time increased. In normotensive patients LVED shortened more (4.4 to 3.86 cm) than in hypertensive children (4.44 to cardiac output 4.18 cm), but there were no significant differences. Significantly decreased only in the normotensive children. In hypertensive children the shortening fraction increased significantly (35.54 to 42.48%) in contrast to normotensive children (40.84 to 38.44%). Cardiac preload (LVES) and (LVED) and afterload (diastolic pressure) was reduced significantly after volume elimination. These changes in cardiac function suggest, that cardiac alterations found before hemodialysis are only functional and not structural.

[A radioimmunoassay for the determination of human myoglobin: lower detection limit, precision and use in control of myoglobinuric kidney failure]. / Radioimmuntest zur Bestimmung von Humanmyoglobin: Untere Nachweisgrenze, Präzision, Verlaufskontrolle beim myoglobinurischen Nierenversagen.

The lower detection limit of a radioimmunoassay for human myoglobin was determined by two "precision from day to day" methods (90% and 3 s methods), and by two "precision in series" methods (95% confidence range and the method of Markowetz & Munz). According to Markowetz & Munz, the lower detection limit (as a measure of sensitivity) is the lowest myoglobin concentration which, in 15-fold assays, shows no binding value in common with that of the next highest concentration, and no activity value in common with that of the reference binding value. On theoretical grounds (precision in series) and from a practical standpoint (determination of the lower detection limit using one sample assay), this method is the most suitable for the determination of the lower detection limit as a measure of sensitivity. It remains to be seen whether this is a valid generalization for other methods.

[Nontraumatic rhabdomyolysis with reversible acute kidney failure following hyperosmolar diabetic coma in a child]. / Atraumatische Rhabdomyolyse mit reversiblem akutem Nierenversagen nach hyperosmolarem diabetischem Koma beim Kind.

A 9 10/12 year year old girl developed severe hyperosmolar diabetic coma, and 5 days later acute renal failure. Extremely elevated levels of myoglobin were measured in serum and urine with a radioimmunoassay kit leading to the diagnosis of atraumatic rhabdomyolysis. Intermittent hemodialysis was performed for 2 weeks. Subsequently myoglobin and creatinine values in serum returned to normal. Psychological disturbances and paresis of the lower extremities subsided 4 resp. 12 weeks after the onset of acute illness.