[Bilateral spastic paresis without the ability to walk]. / Bilaterale spastische Paresen ohne Gehfähigkeit.

BACKGROUND: Developmental disorders and severe damage to major parts of the brain cause loss of motor, sensor, cognitive and mental function. These disorders cannot be medically treated in a sufficiently curative manner and are likely to develop into severe disability in children and adults. THERAPY: Medical nursing care and treatment aims to achieve the best possible quality of life by a lack of pain, ability to communicate, autonomy, and activities of daily life. As part of the team neuro-orthopedic surgeons have to analyze the orthostatic effects of motor functional disorders in order to set up a treatment plan that includes preventive and palliative treatment options by movement therapy, orthotic, medicinal, and surgical interventions. CONCLUSION: Pain and severe progressive deformities, such as contracture of extremity joints, hip dislocation, and spinal deformity must be prevented as far as possible. Activities of daily life should be enhanced by balancing and promoting muscle power and stabilizing weak and unstable parts of the body when possible.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

[Quality assurance in the orthopaedic management of neuromuscular diseases]. / Qualitätssicherung in der Neuroorthopädie.

Increased interest in quality improvement has been brought about by advances in medical technology, health economics and social attitudes over the past decades. Targeted evaluation of infrastructure as well as therapeutic pathways and outcomes can help both patient and carer to achieve optimal treatment processes and a low error rate by means of continuous improvements. While on the one hand there is an urgent need for quality evaluation of health care in disabled persons, on the other this evaluation is challenging since quality of life has to be evaluated for each individual case. Neuroorthopaedic care involves diagnosis, analysis, treatment and rehabilitation of orthopaedic disorders resulting from cerebral and neuromuscular diseases. The aim of treatment is to achieve the best possible quality of life from infancy through to old age, which is measured according to pain-free movement as well as on the ability to actively participate in a social environment. To measure therapeutic outcome, technical methods such as electronic gait analysis, functional scores, questionnaires on subjective satisfaction, as well as economic evaluation of the cost-benefit ratio. Furthermore, medical treatment and technical and logistical processes are evaluated. Evaluation of structure quality provides information on personnel, time, infrastructure, cooperation and knowledge resources.

Decrease of Lp(a) during weight reduction in obese children is modified by the apo(a) kringle-IV copy number variation.

BACKGROUND: Lipoprotein(a) [Lp(a)] is considered an independent risk factor for cardiovascular disease. Its concentration is mainly determined by the kringle-IV repeat copy number variation (CNV) at the apolipoprotein(a) [apo(a)] locus. OBJECTIVE: We aimed to investigate the immediate effect of weight reduction on plasma Lp(a) levels and its dependency on the apo(a) CNV in obese children. DESIGN: We performed a prospective longitudinal intervention study of a low-fat hypocaloric diet conducted in a 3-week dietary camp for obese children. In all, 140 obese participants (54 boys and 86 girls) with a mean age of 12.5+/-1.6 years and a mean relative body mass index (BMI) before treatment of 165.6+/-24.7% were included. Body weight and plasma levels of Lp(a), lipids, apolipoproteins A-I and B, insulin, and C-reactive protein were determined before the onset and after the end of the intervention. In addition, the number of apo(a) kringle-IV repeats were determined using sodium dodecyl sulfate agarose gel electrophoresis. RESULTS: The mean loss of body weight was 5.0+/-1.3 kg (-6.6%), resulting in a mean decrease of the relative BMI of 6.6%. Blood chemistry revealed significant changes in all parameters, especially in Lp(a), with a decrease from 24.4+/-30.6 to 17.9+/-22.6 mg per 100 ml or -19% (P<0.001). The decrease of Lp(a) levels was higher in the group with low compared with high molecular weight apo(a) phenotypes (-23.9 vs -16.6%). CONCLUSIONS: Weight reduction in obese children is associated with significant changes in Lp(a) levels, especially in subjects with high pre-treatment Lp(a) concentrations. This effect is markedly influenced by the molecular phenotype at the copy-number variable apo(a) locus.

[Neuromodulation of spasticity in children by intrathecal baclofen]. / Neuromodulation der Spastik bei Kindern durch intrathekal verabreichtes Baclofen.

INTRODUCTION: Treatment with intrathecal baclofen (ITB) is an important part of the complex therapy of patients with cerebral spasticity aiming to improve the motoric functions and to reduce pain intensity. MATERIAL AND METHODS: ITB was started in the Orthopaedic Hospital in Speising in 1999. From 1999 to 2006 a total of 15 children aged 3 to 16 years old were selected for this special treatment. RESULTS: The average degree of spasticity according to Ashworth (scale 1-5) could be reduced by ITB from 4.38 to 3.0, the time spent sitting could be increased from 3.3 to 5.8h per day and the pain intensity (VAS 1-10) could be reduced from 4.2 to 0.6. The time necessary for nursing treatment was shortened from 7.5 to 3.4 (VAS 1-10). Also improved was the emotional situation, the ability to swallow, the posture of the head and the concentration ability. CONCLUSION: ITB provides neuromodulation even in pediatric patients with complex neuromotoric spasticity.

[The hip joint in neuromuscular disorders]. / Hüftgelenk bei neuromuskulären Erkrankungen.

Physiologic motor and biomechanical parameters are prerequisites for normal hip development and hip function. Disorders of muscle activity and lack of weight bearing due to neuromuscular diseases may cause clinical symptoms such as an unstable hip or reduced range of motion. Disability and handicap because of pain, hip dislocation, osteoarthritis, gait disorders, or problems in seating and positioning are dependent on the severity of the disease, the time of occurrence, and the means of prevention and treatment. Preservation of pain-free and stable hip joints should be gained by balancing muscular forces and by preventing progressive dislocation. Most important is the exact indication of therapeutic options such as movement and standing therapy as well as drugs and surgery.

Determinants of plasma apolipoprotein A-V and APOA5 gene transcripts in humans.

OBJECTIVE: Apolipoprotein A-V (apoAV) contributes to the regulation of triglyceride metabolism, which plays a role in the pathogenesis of atherosclerotic diseases. We therefore ascertained determinants of hepatic APOA5 transcript and apoAV plasma levels in humans. DESIGN: We determined influences of anthropometric variables, biochemical factors related to lipid and glucose metabolism, hepatic mRNA levels transcribed from the APOA1/C3/A4/A5 cluster and transcription factor genes implicated in the regulation of APOA5 as well as common single nucleotide polymorphisms (SNPs) at the APOA5 locus on APOA5 expression in 89 obese patients and 22 non-obese controls. RESULTS: Mean, age and sex adjusted, hepatic APOA5 mRNA or apoAV plasma levels did not differ by obesity status, homoeostasis model assessment insulin resistance or inflammatory markers. In multivariate regression models, the c56C > G SNP, plasma apoCIII, plasma nonesterified fatty acids, hepatic APOA5 transcripts, sex and a weak association with obesity status explained 61% of the variance in apoAV plasma levels. Hepatic transcript levels of carnitine palmitoyltransferase 1 (CPT1A1) and peroxisome proliferator-activated receptor alpha (PPARA), plasma nonesterified fatty acids and the c56C > G SNP explained 48% of the variance in hepatic APOA5 transcript levels. CONCLUSION: Apolipoprotein A-V plasma levels are independently associated with plasma free fatty acid and hepatic APOA5 mRNA levels. Associations of APOA5 transcripts with PPARA and CPT1A1 transcripts suggest that APOA5 expression is intimately linked to hepatic lipid metabolism.

Altered regulation of apolipoprotein A-IV gene expression in the liver of the genetically obese Zucker rat.

Apolipoprotein (apo) A-IV, a structural component of chylomicrons and high-density lipoproteins, may play a role in the catabolism of triglyceride-rich lipoproteins and in reverse cholesterol transport. To study the regulation of apoA-IV gene expression by genetic and nutritional factors, we determined the effect of a fish oil-rich and a sucrose-rich diet on apoA-IV gene transcription and nuclear and total cellular apoA-IV mRNA abundance in livers of genetically obese, hyperlipoproteinemic (fa/fa) Zucker rats and their lean (Fa/-) littermates. In obese rats fed chow, hepatic apoA-IV gene expression was more than twofold higher than in lean rats because of a post-transcriptional mechanism. apoA-I gene expression and apoC-III mRNA levels, studied as controls, were similar in both groups. The fish oil-rich diet reduced total cellular apoA-IV mRNA abundance transcriptionally to 34 +/- 4% of basal values in lean rats, but did not alter apoA-IV gene expression in obese rats. In contrast, this diet reduced apoA-I gene expression in both lean and obese animals. The sucrose-rich diet increased apoA-IV gene expression twofold in both lean and obese rats. Thus, genetic obesity alters the response of hepatic apoA-IV gene expression to a lipid-lowering diet rich in fish oil by a mechanism affecting transcriptional regulation.

Role of thyroid hormones in apolipoprotein A-I gene expression in rat liver.

To study the regulation of hepatic apo A-I gene expression, we measured synthesis and abundance of cellular apo A-I mRNA and its nuclear precursors in livers of hypothyroid and hyperthyroid rats. In hypothyroid animals, both synthesis and abundance of apo A-I mRNA was reduced to half of control values. After injection of a receptor-saturating dose of triiodothyronine into euthyroid rats, apo A-I gene transcription increased at 20 min, reached a maximum of 179% of control (P less than 0.01) at 3.5 h, and remained elevated for up to 48 h. The abundance of nuclear and total cellular apo A-I mRNA increased at 1 and 2 h, respectively, and exceeded the levels expected from enhanced transcription more than two fold at 24 h after hormone injection. Upon chronic administration of thyroid hormones, levels of nuclear and cytoplasmic apo A-I mRNA remained elevated but transcription of the apo A-I gene fell to 42% of control (P less than 0.01). Thus, thyroid hormones rapidly stimulate apo A-I gene transcription. Posttranscriptional events leading to increased stability of nuclear apo A-I RNA precursors become the principal mechanism for enhanced gene expression in chronic hyperthyroidism and may cause feedback inhibition of apo A-I gene transcription. Our results furthermore imply that the majority of hepatic nuclear apo A-I RNA precursors are degraded in euthyroid animals.

Differential regulation of hepatic apolipoprotein A-I and A-II gene expression by thyroid hormone in rat liver.

Apolipoproteins A-I and A-II (apo A-I, apo A-II) are major protein components of high density lipoproteins. Thyroid hormone has a differential effect on the expression of the apo A-I and apo A-II genes in rat liver. Apo A-I gene expression is stimulated by thyroid hormone, whereas apo A-II mRNA abundance is decreased in chronic hyperthyroidism. To determine the regulatory steps involved in this differential effect of thyroid hormone on hepatic apo A-I and apo A-II gene expression, we studied the effect of short term and chronic hyperthyroidism on apo A-I and apo A-II gene transcription rates, nuclear RNA abundance and total cellular mRNA levels. After a single receptor saturating dose of L-triiodothyronine (T3) apo A-II gene transcription was transiently increased to 164% +/- 13% of basal values (P < 0.05) without affecting nuclear apo A-II RNA abundance. Apo A-I gene transcription, however, increased to 158% +/- 8% of baseline levels (P < 0.05) and remained elevated for at least 24 h. Nuclear and total cellular apo A-I mRNA increased more than expected from the increased transcription rate suggesting nuclear RNA stabilization and/or more efficient processing of the primary transcripts. In chronic hyperthyroidism, total cellular apo A-II mRNA abundance decreased to 62% +/- 18% (P < 0.05) and apo A-II gene transcription and apo A-II nuclear RNA were moderately reduced. By contrast, apo A-I nuclear and total cellular RNA were increased several fold by post-transcriptional mechanisms, whereas apo A-I gene transcription was drastically decreased. We conclude that the apo A-I and apo A-II genes in rat liver respond differently to both acute and chronic hyperthyroidism and that their expression is regulated at transcriptional and posttranscriptional levels.

Effect of sucrose diet on expression of apolipoprotein genes A-I, C-III and A-IV in rat liver.

A sucrose-rich diet stimulates hepatic lipogenesis and induces net production of very low density lipoproteins in the liver. To study changes of hepatic apolipoprotein gene expression in response to such a diet, we measured the mRNA abundance of apolipoproteins A-I, C-III and A-IV in livers of rats fed a sucrose-rich diet or a control diet for 3 weeks. In livers of sucrose-fed rats, the abundance of cellular and nuclear apo A-IV mRNA increased to 185% +/- 21% and 142% +/- 22% of control values (P less than 0.01), respectively. In sucrose-fed rats, the transcriptional activity of the apo A-IV gene, measured in a cell-free transcription system using isolated liver nuclei, increased to 144% +/- 23% of control (P less than 0.05). In contrast, this diet neither affected the abundance of cellular and nuclear apo A-I and apo C-III mRNA nor the transcriptional activity of these genes in liver. These results are consistent with specialization of the regulatory elements of the genes coding for apolipoproteins A-I, C-III and A-IV. Alternatively, enhanced transcription of the apo A-IV gene may preclude increased synthesis of apo A-I and/or apo C-III mRNA due to the close linkage of the three genes in the rat genome.

Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis.

This study was performed to investigate the effect of low-density lipoprotein (LDL) immunoapheresis on lipoprotein(a) [Lp(a)] reduction in patients with heterozygous and homozygous familial hyperlipidemia (N=16) and insufficient response to lipid-lowering agents. By desorption of approximately 5,700+/-500 mL of plasma, a mean reduction in total cholesterol of 62% (P < .001) and in LDL-cholesterol of 70% (P < .001) was achieved. Lp(a), which was elevated at study entry in seven of these patients (82.1+/-34.3 mg/dL; range, 48 to 148 mg/dL), was reduced during the initial LDL-apheresis procedure by 74.8%+/-14.1% (P < .001). Long-term apheresis treatment performed at weekly intervals resulted in an mean reduction in Lp(a) pretreatment values to 39.1+/-28.5 mg/dL (-54%; P < .001). Desorbed Lp(a) was measured at the waste of the columns for 31 apheresis treatments. Lp(a) concentration of the column waste was higher in patients with elevated serum Lp(a) pretreatment values as compared with those with Lp(a) serum values within the normal range (elevated Lp(a), 1,420+/-380 mg; without elevated Lp(a), 235+/-190 mg; P < .001). The rate of return of Lp(a) following apheresis treatment scheduled at weekly intervals was comparable to that of LDL-cholesterol.

Up-regulation of LDL-receptor expression by LDL-immunoapheresis in patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by an autosomal dominantly inherited deficiency of LDL-receptor expression on the cell surface, leading to excess plasma LDL-cholesterol and severe premature atherosclerosis. In patients with heterozygous FH, a major therapeutic objective of conventional drug therapy is to stimulate maximally the residual cellular capacity to produce LDL-receptors via inhibition of endogenous cholesterol synthesis. In contrast, LDL-immunoapheresis aims at reducing the plasma LDL-cholesterol level by extracorporeal elimination of LDL particles. The present study investigates whether LDL-immunoapheresis applied in addition to conventional drug therapy is able to further stimulate residual LDL-receptor expression capacity in patients with heterozygous FH via the withdrawal of external cholesterol supply, thereby exerting a second accessory lipid lowering effect. METHODS: LDL-receptor expression--calculated by transforming mean fluorescence intensities into numbers of antibody binding sites per cell (S/C)--was determined flow-cytometrically on peripheral blood monocytes before and after LDL-apheresis. For a comparison with the maximum obtainable receptor expression capacity, in vitro stimulation experiments under completely LDL deficient conditions were performed. RESULTS: Prior to LDL-apheresis, LDL-receptor density was comparable in patients (N = 7; 2014 +/- 359 S/C) and controls (N = 10; 1782 +/- 252 S/C). Under in vitro conditions LDL-receptor expression of controls exceeded that of patients with FH by 1.6 times. Immediately after apheresis, LDL-receptor expression significantly increased to almost the same level as obtained by in vitro stimulation (3640 +/- 423 S/C and 3632 +/- 572 S/C). The LDL-receptor expression in FH subsequent to LDL-apheresis exhibited two patterns of kinetics [Type 1: maximal receptor stimulation (288 +/- 70%; P < 0.07) already during apheresis; Type 2: highest receptor density 24 hours after treatment (149 +/- 11%; P < 0.01)]. CONCLUSIONS: These results demonstrate that despite drug therapy, LDL-apheresis significantly stimulates the residual LDL-receptor expression in FH via the reduction of available extracellular cholesterol resulting in delayed reappearance of hypercholesterolemia in between treatments.

[Botulinum toxin type A in the treatment plan for cerebral palsy]. / Botulinumtoxin Typ A bei Spastizität im Kindesalter.

Over the past decade a number of placebo-controlled studies have confirmed that intramuscular injections of botulinum toxin A (BTX A) has antispastic effects. Cerebral palsy is among the most frequent disorders of the growing locomotor apparatus during childhood. Weakness as well as spasticity due to lack of selective neuronal control causes functional impairment and additional mechanisms of compensation, retardation of motor development, secondary deformities of muscles and soft tissues due to a failure of muscle growth, subluxation/dislocation of joints, early osteoarthritis, and pain. Prevention of this vicious circle has to be the main goal of caring for children with spasticity. Quality of life in children with cerebral palsy can be improved by support of their daily living motor activities. Increased muscle tone can be reduced by physical exercises, by individually adapted orthoses, walkers, and wheelchairs, by manual therapy, serial casting and in certain cases by systemic drugs or by multiple-stage surgical procedures. BTX A can be used to enable these treatment possibilities or to increase their effect. In our clinical study (BTX A in 114 patients in 19952/2000) we found no major side effects. Weakness, pain or swelling occurred temporarily. Indications for the use of BTX A are pain, functional impairment, severe cosmetic problems, as well as prevention of secondary contractures, deformities, and dislocations caused by increased muscle tone. We consider the selection of patients for the use of BTX A and the development of a goal-orientated treatment plan by multidisciplinary team approach as the most important steps. Prerequisites are exact statomotoric and dynamic physical examinations, and standardised movement analysis. 3-D-gait analysis and dynamic electromyography is used in cases where functional improvement of gait is the goal of BTX A-treatment.

[Direct detection of Toxoplasma gondii with polymerase chain reaction in diagnosis of fetal toxoplasma infection]. / Direkter Nachweis von Toxoplasma gondii mit Polymerase-Kettenreaktion zur Diagnostik einer fetalen Toxoplasma-Infektion.

Primary infection with Toxoplasma gondii during pregnancy may affect the fetus and result in congenital toxoplasmosis. In Austria serological screening for detection of newly acquired infection during pregnancy was introduced in 1975. In this study we used polymerase chain reaction (PCR) for detection of fetal infection with Toxoplasma gondii. Amniotic fluid samples were analyzed from 11 women with serological indication of acute toxoplasmosis infection. Nine of these women had already received treatment prior to amnio-centesis and no evidence of Toxoplasma gondii DNA was detected with PCR in the respective amniotic fluid samples. Isolation of the organism by mouse inoculation was negative in these cases and follow-up serology as well as clinical examination of the infants confirmed these results. In 2 patients investigation of the amniotic fluid samples by means of PCR was positive; both women had not yet been treated at the time of amniocentesis. Our results indicate that identification of Toxoplasma gondii in amniotic fluid is a useful procedure for diagnosing or excluding fetal infection. Moreover, the current recommendations of the screening program appear to be successful in preventing congenital toxoplasmosis.

Die Patellaluxation.

ZUSAMMENFASSUNG: 1. Die chronisch habituelle Patella(sub)luxation aufgrund einer angeborenen Fehlbildung als Kniescheibenstabilisatoren, die in seltenen Fällen bereits postpartal als kongenitale Patellaluxation vorliegen kann.Die chronisch rezidivierende Patella(sub)luxation infolge einer sekundären Instabilität des Kapselbandapparates, häufig nach einer akuten traumatischen Luxation der Patella.