Genotypic and phenotypic spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency.

OBJECTIVES: Pathogenic biallelic variants in PCK1 coding for the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) cause PEPCK-C deficiency, a rare disorder of gluconeogenesis presenting with hypoglycemia, lactic acidosis, and hepatopathy. To date, there has been no systematic analysis of its phenotypic, biochemical, and genetic spectrum. METHODS: All currently published individuals and a novel patient with genetically confirmed PEPCK-C deficiency were included. Clinical, biochemical, and genetic findings were analyzed. Protein and in-silico prediction score modeling was applied to analyze potential variant effects. RESULTS: Thirty-two individuals from 25 families were found, including one previously unreported patient. The typical biochemical pattern was hypoglycemia triggered by catabolic situations, elevated urinary concentrations of tricarboxylic acid cycle metabolites, mildly elevated alanine and aspartate aminotransferase and elevated lactate concentrations in serum. Plasma glutamine concentrations were elevated in some patients and may be a suitable marker for newborn screening. With adequate treatment, biochemical abnormalities usually normalized following a hypoglycemic episode. Symptom onset usually occurred in infancy with a broad range from neonatal age to adulthood. Regardless of the genotype, different phenotypes with a broad clinical spectrum were found. To date, eight genotypes with nine different PCK1 variants were identified, of which alleles with the recurrent variant c.925G > A; p.(Gly309Arg) are predominant and appear to be endemic in the Finnish population. Protein modeling suggests altered manganese- and substrate-binding as superordinate pathomechanisms. CONCLUSIONS: Environmental factors appear to be the main determinant for the phenotype in patients with biallelic variants in PCK1. Based on the biochemical pattern, PEPCK-C deficiency is a recognizable cause of childhood hypoglycemia. It is a treatable disease and early diagnosis is important to prevent metabolic derailment and morbidity. Newborn screening can identify at least a sub-cohort of affected individuals through elevated glutamine concentrations in dry blood.

[Structured rehabilitation after lumbar spine surgery : subacute treatment phase]. / Strukturierte Rehabilitation nach lumbaler Wirbelsäulenoperation : Subakute Behandlungsphase.

BACKGROUND: There are currently no uniform standards regarding rehabilitation of patients after lumbar spine surgery. Due to significant improvements in surgical methods in recent years, an increase in postoperative training intensity is now possible. Conservative rehabilitation has yet to adapt to this reality. Earlier initiation of structured rehabilitation after the acute phase is often regarded with skepticism. OBJECTIVE: To evaluate the effect of structured rehabilitation after lumbar spine surgery in the early phase of treatment (2 weeks after surgery), a group of seven spinal surgery clinics, two inpatient and three outpatient rehabilitation centers in the Rhine-Main area in Germany was formed. MATERIALS AND METHODS: In this prospective study, 124 patients were divided into groups (A/B/C) by their surgeon, regardless of diagnosis and surgical procedure. For each group of participants, the content of therapy was preplanned. RESULTS: The statistical analysis using the visual analog scale (VAS), Oswestry Disability Index (ODI), and short form-12 health survey (SF-12) to evaluate changes in impairment caused by back pain and in health-related quality of life was evaluated. In all three groups, significant improvements in VAS, ODI, and SF-12 were shown. Re-operation was unnecessary due to the absence of postoperative complications. CONCLUSION: A structured postoperative rehabilitation program results in significant improvements in the parameters of pain and quality of life, and does not increase the risk of postoperative complications.

Nanomembrane quantum-light-emitting diodes integrated onto piezoelectric actuators.

We integrate resonant-cavity light-emitting diodes containing quantum dots onto substrates with giant piezoelectric response. Via strain, the energy of the photons emitted by the diode can be precisely controlled during electrical injection over a spectral range larger than 20 meV. Simultaneously, the exciton fine-structure-splitting and the biexciton binding energy can be tuned to the values required for entangled photon generation.

[Evaluation of left ventricular volumes in patients with congenital heart disease and abnormal left ventricular geometry. Comparison of MRI and transthoracic 3-dimensional echocardiography]. / Vergleich der transthorakalen 3D-Echokardiographie mit der MRT zur Bestimmung linksventrikulärer Volumina bei Patienten mit pathologischer Ventrikelgeometrie aufgrund angeborener Herzfehler.

PURPOSE: To assess the new method of 3-dimensional echocardiography in comparison to the "gold standard" MRI as to its ability to calculate left ventricular volumes in patients with congenital heart disease. MATERIALS AND METHODS: Eighteen patients between the ages of 3.9 to 37.3 years (mean: 12.8 +/- 9.7) with a geometrically abnormal left ventricle were examined using a 1.5T scanner with a fast gradient-echo sequence (TR = 14 ms, TE = 2.6 - 2.9 ms, FOV = 300 - 400 mm, flip angle = 20 degrees, matrix = 128 : 256, slice thickness = 5 mm, retrospective gating) in multislice-multiphase technique. Transthoracic 3D-echocardiography was performed with a 3.5 MHz transducer and a Tomtec (Munich, Germany) system for 3D reconstruction. RESULTS: Volume calculation was possible in all patients with 3D-echocardiography, but the muscle mass calculation only succeeded in 11 of 18 patients (61 %) due to inadequate visualization of the entire myocardium. Comparing MRI and 3D-echocardiography, the correlation was r = 0.97 for the end-systolic volumes, r = 0.98 for the end-diastolic volumes, r = 0.79 for the end-systolic muscle mass and r = 0.77 for the end-diastolic muscle mass. The agreement between both methods was considered good for the calculated end-diastolic volumes and sufficient for the calculated end-systolic volumes. The muscle mass calculations showed larger differences especially for the end-systolic mass. Mean intraobserver variability was 18.6 % for end-systolic and 8.3 % for end-diastolic volumes. CONCLUSION: In patients with an abnormal left ventricular configuration due to congenital heart disease, the new method of 3D-echocardiography is sufficient for volume calculations in preselected patients. The high intraobserver variability is still a limitation of transthoracic 3D-echocardiography in comparison to MRI.

A nonsense codon of exon 14 reduces lysyl hydroxylase mRNA and leads to aberrant RNA splicing in a patient with Ehlers-Danlos syndrome type VI.

Ehlers-Danlos syndrome type VI (EDSVI) is an autosomal recessively inherited connective tissue disease, characterized by kyphoscoliosis, muscular hypotonia and ocular manifestations. The cause of the syndrome is a deficiency in the activity of lysyl hydroxylase (LH), one of the enzymes involved in the post-translational modification of collagens. We describe here an unusual compound heterozygote British patient with EDSVI. Our investigations indicate that a maternally inherited nonsense mutation (Y511X) in exon 14 of the LH gene (PLOD1) results in a reduction of the mRNA level as well as a skipping of exon 14 sequences in the mRNA that produces a protein shortened by 38 amino acids. The transcription of the other allele of the LH gene is considerably reduced from the normal for reasons that are not yet known. As a consequence, the LH activity of the skin fibroblasts of the patient is markedly reduced.

Electromyographic and gait analysis of forty-three patients after rotationplasty.

BACKGROUND: Rotationplasty is considered to be a treatment option for patients who have had a primary malignant bone tumor of the distal part of the femur or the proximal part of the tibia. The present study was performed to evaluate the muscle activity, the kinetics (range of motion of the hip and knee joints), and the kinematics (joint moments) after rotationplasty and to determine whether there was an association between these parameters and the functional outcome. METHODS: Forty-three patients who had been managed with rotationplasty for the treatment of a femoral or tibial bone tumor were evaluated clinically and functionally. The mean age (and standard deviation) at the time of follow-up was 24.4 +/- 10.7 years (range, eight to sixty-eight years), the mean age at the time of the procedure was 17.8 +/- 10.2 years (range, seven to sixty-three years), and the mean duration of follow-up was 6.7 +/- 4.9 years (range, 0.7 to eighteen years). Instrumented gait and electromyographic analyses were performed. The qualitative data were compared with the functional outcome, which was determined with the functional evaluation score of the Musculoskeletal Tumor Society. RESULTS: Gait analysis revealed a fairly normal walking pattern with a slight limp and a lateral lean of the trunk over the ipsilateral limb that led to a reduced joint moment in the hip (moment on involved side, 68 percent [compared with a control group]; moment on uninvolved side, 81 percent). The ranges of motion of the hips (uninvolved side, 42.0 +/- 8.2 degrees; involved side, 42.4 +/- 8.0 degrees) and the knees (uninvolved side, 59.7 +/- 5.0 degrees; involved side [former ankle joint], 58.1 +/- 11.6 degrees) were symmetrical even though the knee-motion pattern of the involved limb indicated a slightly reduced extensor mechanism in 51 percent (twenty-two) and a markedly reduced extensor mechanism in 35 percent (fifteen) of the forty-three patients. Electromyography revealed function of the muscles of the involved limb, with comparable amplitudes in the involved and uninvolved limbs. The leg muscles of the involved limb were active in the stance phase (the soleus and the lateral and medial heads of the gastrocnemius) and the swing phase (the peroneus longus and the tibialis anterior) according to their function in relation to the new knee joint. The patients had a good functional result, with a mean score of 23.9 +/- 2.7 of 30 points. With the numbers available for study, we could not show the duration of follow-up to be related to the overall outcome, but the age at the time of the operation was related to the total functional score as well as to gait and walking ability (p < 0.05). CONCLUSIONS: The results of the electromyographic and gait analyses demonstrated good functional restoration of gait following rotationplasty.

The 'Entlastungsgang'. A hip unloading gait as a new conservative therapy for hip pain in the adult.

'Entlastungsgang' is a gait modification aiming to unload the hip joint by producing a modified Duchenne-limp (straight spinal column, additional lifting of the pelvis on the side of the swinging leg and a consecutive side shift of the pelvis) and a wide stance gait. Sixteen patients suffering from hip pain caused mainly by hip dysplasia were investigated. They received daily gait training for 12 h combined with intensive physical therapy as in-patients for 3-4 weeks. The external muscle torque acting on the hip joint was determined by 3D-gait analysis before, during and after the gait training. We found a reduction of the muscle torque after gait training to 77.2% of the initial value. At an average follow up of 12 months we found a persisting reduction of the muscle torque to 87. 0% at spontaneous gait that was further reduced to 81.3% of the initial value. The hip score for two components of the Merle d'Aubigne and Postel score for pain and walking was significantly improved from 7.4 to 10.8 points.

A compound heterozygote patient with Ehlers-Danlos syndrome type VI has a deletion in one allele and a splicing defect in the other allele of the lysyl hydroxylase gene.

We report the first deletion mutation and the first splicing defect in the lysyl hydroxylase gene in a compound heterozygote patient with Ehlers-Danlos syndrome type VI with markedly reduced lysyl hydroxylase activity. Northern analysis of the RNA isolated from skin fibroblasts of the patient demonstrated the presence of a truncated lysyl hydroxylase mRNA. PCR and sequence analysis confirmed the truncation and indicated that the cells contain two types of shortened mRNAs, one lacking the sequences corresponding to exon 16 and the other lacking that corresponding to exon 17 of the lysyl hydroxylase gene. Analysis of genomic DNA revealed deletion of the penultimate adenosine from the 3' end of intron 15 from one allele. This defect was probably responsible for the skipping of exon 16 sequences from the transcript. The other allele, inherited from the mother, contains an Alu-Alu recombination with a deletion of about 3,000 nucleotides from the gene; this abnormality explains the lack of exon 17 sequences. The identified mutations in exon 16 and exon 17 do not alter the reading frame of the transcripts.

Epidural abscess after combined spinal-epidural block.

PURPOSE: We report the first case of abscess formation after combined spinal-epidural block (CSE). Penetration of the dura in CSE may constitute an additional risk of subarachnoid spread of bacteria when post-puncture epidural infection is present. CLINICAL FEATURES: The combination of a spinal and a continuous epidural block (CSE) using a needle through needle technique was used in a 72-yr-old man for reconstructive vascular surgery of the lower limb. On the fourth postoperative day the patient demonstrated back pain, fever, and exudation of pus from the CSE-puncture site. An epidural abscess was diagnosed by magnetic resonance imaging and subsequently an emergency hemiaminectomy was performed. Physical examination and surgery did not show evidence of bacterial spread into the subarachnoid space. CONCLUSION: Epidural abscess formation after CSE may increase the risk of bacterial spread into the subarachnoid space. In this case spontaneous exudation and surgical drainage of abscess material may have prevented intrathecal infection. Rapid diagnosis and treatment of an epidural abscess appears particularly essential after CSE to prevent neurological sequelae.

Recovery of psychomotor function following general anaesthesia in children: a comparison of propofol and thiopentone/halothane.

The present study was undertaken to compare immediate recovery and recovery of complex psychomotor function in 20 children (aged 6-12 years) following general anaesthesia with either thiopentone/halothane or propofol. Early recovery of psychomotor skills was significantly faster in the propofol group than in the thiopentone/halothane group. Compared to preanaesthesia baseline the sedation and cooperation scores, the reaction time to visual and auditory stimuli as well as the postbox test and the flicker fusion frequency were less impaired after propofol than after thiopentone/halothane anaesthesia up to 120 min postoperatively. In the propofol group most tests reached preanaesthesia levels after 120 min, while in the thiopentone/halothane group these levels were not reattained throughout the entire study period. The results indicate that the recovery of psychomotor function in paediatric patients following general anaesthesia with propofol is significantly faster than with thiopentone/halothane. This has important implications for parental satisfaction, the time over which patients need to be monitored in the recovery room and for the discharge criteria after daycase surgery.

Lignocaine metabolite formation: an indicator for liver dysfunction and predictor of survival in surgical intensive care patients.

Formation of the lignocaine metabolite monoethyl-glycine-xylidide (MEGX) by hepatic cytochrome P450 enzymes is a new method for evaluating liver function. The purpose of this study was to compare MEGX formation with other liver function parameters in surgical intensive care unit patients. The study include 29 critically ill patients who had been admitted to the unit for more than 3 days with a median APACHE III score-predicted mortality > 30%. On day 4, lignocaine was given intravenously at a dose of 1 mg.kg-1 over 2 min and MEGX formation was measured 15 min later. Eighty-nine percent of the patients had MEGX values below 90 micrograms.l-1 indicating impaired liver function. Eleven patients died, 18 patients survived. The group of patients with fatal outcome had significantly lower MEGX values (median: 23 micrograms.l-1) than the group of survivors (median: 53 micrograms.l-1, p < 0.01). Bilirubin values were elevated in the non-survivor group (median: 2.8 mg.dl-1) compared to the survivors (median: 0.9 mg.dl-1, p < 0.05). There was no significant difference between two groups in the other liver function tests. We conclude from our results that the MEGX test can be considered an indicator for hepatic dysfunction and predictor of survival in critically ill patients.

Marked reduction of Tamm-Horsfall protein synthesis in hyperprostaglandin E-syndrome.

Hyperprostaglandin E-syndrome (HPS), a recently described variant of Bartter's syndrome (BS), resembles BS in a number of symptoms but is distinct from BS in others. Similar to BS, HPS is characterized by congenital hypokalemic alkalosis, hypertrophy of the juxtaglomerular apparatus, hyperreninemia, secondary hyperaldosteronism, normal blood pressure and renal diabetes insipidus. Other than BS, HPS is constantly associated with chronic hypercalciuria and nephrocalcinosis as well as both renal and systemic PGE2 overproduction. Correction of most of the symptoms in HPS is achieved by permanent inhibition of prostaglandin synthesis with indomethacin. Among the causes leading to HPS, a selective damage of the distal tubule in HPS has been suggested. Therefore, synthesis of Tamm-Horsfall protein (THP), a glycoprotein exclusively produced in the thick ascending limb of the loop of Henle, was measured by ELISA in the urine of seven infant HPS patients (aged 3 to 8 years). Patients were investigated both under constant indomethacin treatment and after a one week period without indomethacin. Nine healthy children (aged 5 months to 10 years) served as controls. In controls mean daily THP excretion was 54.2 +/- 13.9 (median 46.0) mg/24 hr/1.73 m2 whereas in HPS, THP levels were strongly diminished. During withdrawal of indomethacin treatment, mean THP level was 12.7 +/- 10.1 (median 7.2) mg/24 hr/1.73 m2 and 10.3 +/- 10.1 (median 3.5) mg/24 hr/1.73 m2 under indomethacin treatment, respectively. THP excretion values both without indomethacin and under indomethacin treatment were significantly different from controls (P < or = 0.005); however, there was no significant difference between the THP levels during or after cessation of indomethacin treatment. Creatinine clearance in HPS patients was 75.1 +/- 15.9 (median 76.2) ml/min/1.73 m2 without indomethacin and 81.9 +/- 15.1 (median 83.0) ml/min/1.73 m2 under indomethacin treatment. Control values were not obtained. Comparative measurements of THP excretion in six classical BS-patients (aged 3 months to 17 years) revealed normal THP values in two individuals and intermediate levels in the others: the mean level of six BS patients was 30.8 +/- 13.5 (median 25.0) mg/24 hr/1.73 m2 and was thus significantly higher than in HPS both with and without indomethacin treatment (P < or = 0.05). Immunohistochemistry in renal biopsies of three of the HPS patients showed a strong reduction of cortical tubular THP immunoreactivity in two cases and a less pronounced reduction in the third. In situ hybridization using a THP-riboprobe in these three biopsies revealed significantly reduced or absent THP-mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Protein kinase C stimulation enhances the process formation of adult oligodendrocytes and induces proliferation.

Oligodendrocytes (OL) isolated from adult pig brains regenerate their processes and form a network of fibers after 14-18 days in vitro (DIV). Stimulation of protein kinase C (Pk-C) by tumour promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) produces at day 7 in vitro a similar network after only 20 hr. H-7, an inhibitor of Pk-C, as well as amiloride, which inhibits the subsequent Na+/H+ exchange, reversibly suppress this effect. Activation of the protein kinase A or calmodulin pathway do not result in an increased OL process production. Furthermore, TPA induced proliferation in a subpopulation of OL. We conclude that the stimulation of Pk-C is of utmost importance for OL regeneration.

[SPECT of the brain using 99mTc-HMPAO in patients with cerebrovascular disease: a comparison with CT. A report of 100 cases]. / SPECT des Gehirnes mit 99mTc-HMPAO bei Patienten mit zerebrovaskulärer Erkrankung: Vergleich mit der CT. Bericht über 100 Fälle.

In a retrospective study the sensitivity of SPECT and CT in detecting changes in cerebrovascular disease is compared, based on a group of one hundred patients. The higher sensitivity of SPECT with regard to right-positive results, especially in TIA and PRIND and the markedly lower number of false-negative results are underlined and discussed. The fact that both methods reveal only a slight sensitivity regarding the detection of changes in the basal regions of the brain is also pointed out, with SPECT proving to be the more sensitive of the two methods.

DNA distribution pattern in chronic gastritis. I. DNA ploidy and cell cycle distribution.

DNA distribution patterns were flow cytometrically recorded in gastric biopsy specimens from patients with chronic gastritis (CG) and chronic atrophic gastritis (CAG). DNA aneuploidy was found in 3 of 58 patients with CG and in 7 of 82 patients with CAG. Cell cycle analysis disclosed significantly higher percentages of cells in S-phase and G2M-phase, respectively, in CAG than in CG. With regard to the proliferative activity the total CAG group could be partially differentiated by the degree of severity. CAG with total atrophy showed significantly higher percentages of cells in S-phase than CAG with mild and moderate atrophy. CAG without dysplasia showed lower percentages of cells in S-phase and G2M-phase than CAG with severe dysplasia (p greater than 0.05). The occurrence of intestinal metaplasia was correlated to a significantly higher percentage of cells in G2M-phase.

[An unusual thickening of the gallbladder wall in cholecystitis]. / Aussergewöhnliche Verdickung der Gallenblasenwand bei Cholezystitis.

This is a report on a massive thickening of the gallbladder wall accompanying an acute cholecystitis with cholelithiasis. The sonographic criteria for the diagnosis of cholecystitis are discussed. It is pointed out that a thickening of the gallbladder wall is not a specific sign for cholecystitis.