Primary care development. Family values.
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Primary Health Care↗
Biomedical subjects
M Fischer
Publications and source records attributed to M Fischer.
No propagation of prions in mice devoid of PrP.
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Animals↗
PrP-deficient mice are resistant to scrapie.
Prusiner proposed that the infectious agent of scrapie, the prion, is PrPSc, a modified form of the normal host protein PrPC. Prn-p0/0 mice devoid of PrPC showed normal development and behavior. When inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 16 months while wild type controls all died within 6 months. Propagation of infectivity in the PrP null mice, if any, was less than 10(-5) that in wild type animals. Surprisingly, heterozygous Prn-p0/+ mice also showed enhanced resistance to scrapie. After introduction of Syrian hamster PrP transgenes, Prn-p0/0 mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrPC, possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.
Animals↗
Local disorder studied in SrTiO3 at low temperature by EXAFS spectroscopy.
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Journal Article↗
Susceptibility to scrapie in mice is dependent on PrPC.
Mice devoid of functional PrP genes (Prn-p(o/o) mice) showed normal development and behaviour. When inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 18 months whereas wild-type controls all died within 6 months. No propagation of infectivity could be detected in the PrP null mice. Surprisingly, heterozygous Prn-p(o/+) mice also showed enhanced resistance to scrapie. After introduction of Syrian hamster PrP transgenes, Prn-p(o/o) mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrPC, possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.
Animals↗
A prospective study of the migration of two acetabular components. PCA versus RM cups.
Fifty-nine PCA cups and 61 hydroxyapatite-coated RM cups were included in a prospective randomised study with a mean follow up of 5.2 years. Clinical evaluation revealed better results with the RM cup. Radiological criteria of loosening could be applied only with considerable restrictions as different parameters were assessed: progressively loosened beads in PCA cups and faded contour in RM cups. Migration was measured by a computer assisted method (EBRA). PCA cups showed significantly more longitudinal migration 2 years after operation and subsequently. High migration values correlated with a limp. Loosening as defined by migration was of clinical relevance, could be measured early and predicted the survival rate.
Activities of Daily Living↗
High-dose intravenous melphalan in a patient with multiple myeloma and oliguric renal failure.
A kappa light-chain myeloma was diagnosed as the underlying disease in a 52-year-old woman with acute oliguric renal failure. The patient was erroneously treated with high-dose intravenous melphalan (60 mg/m2). Because of this overdose treatment with granulocyte colony-stimulating factor was initiated, but pronounced absolute leukopenia (white blood cell count < 0.5 x 10(9)/l) developed and lasted for 13 days. Following melphalan treatment a continuous increase in urine volume was accompanied by a decrease of serum creatinine and blood urea nitrogen. Within 10 days after the administration of melphalan the patient no longer required hemodialysis. We conclude that high-dose chemotherapy in combination with hematopoietic growth factors should be considered in individual cases with newly diagnosed light-chain nephropathy.
Acute Kidney Injury↗
Temporal coordination of alternative and simultaneous aiming movements of constrained timing structure.
Two experiments are reported addressing the preparation and initiation of movements with equal or unequal timing properties for both hands. Temporal coordination was examined in two movement tasks: one in which both hands performed the movements simultaneously (simultaneous aiming task) and one in which only one alternative of two possible movements was executed (choice aiming task). For each task a different group of subjects was used. Besides the timing relationships between both movements, the effects of preparation interval (1, 3, and 5 s), the average velocity (7, 14, 17.5, and 70 cm/s), the presence of advance information about the required velocity of the movement(s), and practice were investigated. Based on the common- and the specific-timing notions, distinct hypotheses were tested as to the effects of the variables on the temporal coordination as revealed by reaction time. A main result was that the effects of timing differences between the hands was task specific. For the choice task the data are in agreement with the common-timing notion of coordination, i.e., only one timing demand at a time can be prepared, whereas in the simultaneous task evidence was obtained for the specific-timing notion, i.e., independent preparation and initiation of different timing properties for the hands. However, it is argued that the results of the choice task probably do not reflect a general inability to prepare movements of different timing requirements for both hands, but is related to a task-specific strategy of selective preparation.
Adult↗
RUDER--a prospective, two-year, multicenter study of risk factors for duodenal ulcer relapse during maintenance therapy with ranitidine. RUDER Study Group.
In a prospective study of the risk factors for duodenal ulcer relapse during maintenance (150 mg daily) ranitidine therapy, 1899 patients with chronic ulcer disease were recruited to a multicenter, German trial. Healing of all ulcers was confirmed endoscopically; endoscopy was also obligatory after one and two years or if the patients presented in the interim with symptoms of ulcer relapse. By the end of the first year, 247 patients had experienced at least one relapse and, by the end of the second year, 432 patients had relapsed at least once. The crude one- and two-year relapse rates were 13.0% (95% CI 11.5-14.5) and 22.7% (20.9-24.6%), respectively. Univariate analysis indicated that all seven prospectively defined risk factors were associated with an increased two-year relapse rate; of these, duodenal erosions distant from the healed ulcer [odds ratio (95% CI): 2.23 (1.59-3.15); P < 0.0001], smoking, past or present [1.46 (1.12-1.90); P = 0.0050], psychological stress [1.38 (1.09-1.74); P = 0.0085], heavy physical labor [1.45 (1.06-1.98); P = 0.0219], and absence of NSAID intake [1.54 (1.01-2.29); P = 0.0464] were independent risk factors on stepwise logistic regression analysis, whereas persistent symptoms at healing [1.29 (1.03-1.62), P = 0.0310] and frequent prior relapses [1.45 (1.01-2.04); P = 0.0454] were not. Multiple relapses in 107 patients [5.63% (4.60-6.67%)] were associated with duodenal erosions, smoking, stress, and heavy physical labor.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element.
Mice homozygous for the spastic mutation (spa) suffer from a complex motor disorder resulting from reduced CNS levels of the adult glycine receptor isoform GlyRA, which is composed of ligand-binding alpha 1 and structural beta polypeptides. The beta subunit-encoding gene (Glyrb) was mapped near the spa locus on mouse chromosome 3. In spa/spa mice, aberrant splicing of the beta subunit pre-mRNA strikingly diminishes the CNS contents of full-length transcripts, whereas truncated beta subunit mRNAs accumulate. This is a result of exon skipping, which causes translational frameshifts and premature stop codons. Intron 5 of the spa Glyrb gene contains an L1 transposable element that apparently is causal for the aberrant splicing of beta subunit transcripts.
Amino Acid Sequence↗
Structure, diversity and synaptic localization of inhibitory glycine receptors.
The inhibitory glycine receptor (GlyR) mediates postsynaptic inhibition in spinal cord, brain stem and other regions of the vertebrate central nervous system. Biochemical and molecular approaches have identified different developmentally and regionally regulated GlyR isoforms that result from the differential expression of at least four genes coding for different variants of the ligand-binding alpha subunit. Molecular studies have allowed identification of GlyR subunit domains implicated in ligand binding, channel formation and receptor assembly. At the postsynaptic membrane, the GlyR colocalizes with a 93-kDa tubulin-binding peripheral membrane protein, gephyrin. Antisense inhibition of gephyrin expression prevents GlyR accumulation at postsynaptic membrane specialization. Thus, gephyrin is essential for postsynaptic receptor topology.
Animals↗
The palmar wrist ligaments revisited, clinical relevance.
In fifteen cadaver wrists and ten foetus wrists palmar ligaments were studied. As a result, the palmar scapho-triquetral ligament was presented by means of gross anatomical study, MR imaging, and histological study. A kinematic study was conducted on three cadaver wrists to analyze patterns of motion on the proximal carpal row bones based on the helical axis concept. Motion analysis showed that the scaphoid has a set of helical axes bundled at the radial side of the wrist. On the contrary, the triquetrum had axes bundled on the ulnar side, approximately in the same position as the lunate. That shows that the lunate and triquetrum are coordinated in motion and opposed to that of the scaphoid. The structure possibly ruling this pattern of motion could be the palmar scapho-triquetral ligament, whose insertions on the scaphoid and triquetrum are close to the crossing-point of the helical axes of the scaphoid and triquetrum/lunate, respectively. In order to study the clinical relevance of our findings, a prospective clinical study on 53 patients after wrist injury was conducted. All patients were clinically examined, simple and semi-stress X-rays were taken, and arthrography and arthroscopy performed. Ligament tears were often found, but any correlation to clinical findings or arthrography could not be found. However, high correlation could be found between the lesion of the palmar scapho-triquetral ligament and a DISI position of the lunate combined with increased scapho-lunate angle. It can be concluded that the tear of the palmar scapho-triquetral ligament causes instability pattern that is radiologically evident at an early stage.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Glucosamine sulfate in osteoarthritis of the knee.
Glucosamine sulfate is a drug used for the treatment of osteoarthritis (OA), based on its pharmacological and metabolic activities on the cartilage and chondrocytes, complemented by mild anti-inflammatory properties and a favorable pharmacokinetic profile. The aim of this study was to define the activity and safety of glucosamine sulfate on the symptoms of patients with OA, using a multicenter, randomized, placebo-controlled, double-blind, parallel-group study design. The study included 252 outpatients with OA of the knee (Lequesne's criteria), radiological stage between I and III, and Lequesne's severity index of at least 4 points and symptoms for at least 6 months. Patients were treated with either placebo or oral glucosamine sulfate 500 mg t.i.d. for 4 weeks, with weekly, with weekly clinic visits. Responders to treatment were defined as patients with a reduction of at least 3 points in the Lequesne's index with a positive overall assessment by the investigator. The Lequesne's index was 10.6 +/- 0.45 S.E.M. points in both groups at the start of the study. This decreased to 7.45 +/- 0.5 points in the treatment group (average 3.2) and 8.4 +/- 0.4 points in the placebo group (average 2.2) (P < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (N = 120) vs 38% with placebo (N = 121). These proportions were 52% vs 37% in an intention-to-treat analysis (P = 0.014 and 0.016, respectively; Fisher's Exact Test). The medications were well tolerated throughout the study, with no difference between the glucosamine and placebo treated groups. It is concluded that glucosamine sulfate may be a safe and effective symptomatic Slow Acting Drug for OA.
Administration, Oral↗
NMR imaging of the apparent diffusion coefficient (ADC) for the evaluation of metabolic suppression and recovery after prolonged cerebral ischemia.
Adult normothermic cats were submitted to 1-h complete cerebrocirculatory arrest by intrathoracic occlusion of the internal mammary, the innominate, and the subclavian arteries in combination with pharmacologically induced hypotension. After ischemia, recirculation was initiated at different blood pressure levels to manipulate the postischemia resuscitation conditions. The resulting spectrum of postischemic recovery was studied by combining nuclear magnetic resonance imaging of the apparent diffusion coefficient (ADC) with pictorial assays of brain tissue pH, ATP, glucose, and lactate. Before ischemia, the mean ADC (average of seven coronal slices of five cats) was 713 +/- 40 x 10(-6) mm2/s. After 10-min ischemia, ADC declined to 68% of control and after 50 min slightly further to 63% of control. During recirculation after 1-h ischemia, recovery of ADC varied depending on the initial reperfusion pressure and other systemic variables. In two animals ADC only transiently increased followed by a secondary decline below the postischemic level. In three other animals ADC returned to near control within 1 h of recirculation. The comparison of ADC changes with previously reported changes in extracellular volume revealed a close relationship, supporting the notion that ADC is a function of the intra/extracellular water compartmentation. Recovery of ADC correlated closely with tissue pH and metabolic recovery, studied 3 h after the initiation of recirculation. Animals without recovery of ADC exhibited global depletion of ATP and glucose and severe lactacidosis, whereas animals with recovery of ADC showed replenishment of ATP and glucose to near control and a substantial reversal of lactacidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Catheter-induced thromboses--duplex ultrasound studies of incidence and extent].
The aim of the study was to detect the frequency and the extension of thrombosis caused by central venous catheters by means of Doppler-duplex ultrasound. 36 patients were examined. The visualization rate of catheters in jugular (91%) and femoral (62%) veins was excellent. In contrast, catheters in the subclavian vein could be detected only in 33 per cent of all cases. As a result the overall patency rate of catheters was only 37 per cent after a period between 8 hours and 60 days (12.2 +/- 11.3 days) following the introduction. There was no significant relation between the type of catheter, the management with central venous catheters and the rate of thrombosis.
Adolescent↗
Elimination of amino acids in renal failure.
The elimination of intravenously infused amino acids was evaluated in six patients with acute renal failure (ARF), 6 with conservatively treated chronic renal failure (CRF), 6 subjects receiving regular hemodialysis treatment (RDT), and 5 healthy control subjects. In ARF, CRF, and RDT groups, whole-body clearance (Cltot) of the 10 amino acids was elevated (113.5 +/- 1.5; 94.2 +/- 1.5 and 127.6 +/- 12.4, respectively, vs 85.2 +/- 4.8 mL.kg-1.min-1 in control subjects, P < 0.001). In ARF, Cltot of histidine, lysine, and methionine was higher and Cltot of phenylalanine and valine was lower as compared with control subjects. In CRF, Cltot of tryptophan and histidine was elevated and Cltot of phenylalanine was reduced; in RDT, Cltot of histidine, methionine, tryptophan, lysine, isoleucine, and leucine was raised. In all groups the relative clearance (% of total clearance) of phenylalanine and valine was reduced, and relative clearance of histidine and tryptophan was elevated. We conclude that in renal failure the elimination of amino acids from the intravascular space is profoundly altered and that the pattern of metabolic aberrations is similar in ARF, CRF, and RDT groups.
ADP-Ribosylation Factor 6↗
The prevalence of poor anticoagulant response to activated protein C (APC resistance) among patients suffering from stroke or venous thrombosis and among healthy subjects.
A poor anticoagulant response to activated protein C (APC) in an activated partial thromboplastin time (aPTT) assay (APC resistance) was recently reported to be a cause of familial thrombophilia. The response to APC was measured in 30 patients suffering from juvenile or recurrent stroke, in 40 patients suffering from venous thromboembolism and in 50 healthy subjects. The prevalence of APC resistance was found to be significantly higher among patients with stroke (20%, P < 0.003) and venous thrombosis (17.5%, P < 0.02) compared with the prevalence of APC resistance among normal controls (2%). In one case of venous thrombosis, the proposita's family (A) could be investigated and in five out of nine investigated members (56%) a poor or borderline response to APC was detected. The family (B) of another APC-resistant patient revealed six subjects with poor coagulation response to APC out of eight family members studied (75%). Measuring protein S activity with an automated calcium-thromboplastin-based protein S activity assay, a significant correlation (P < 0.0001) between the results of this functional protein S assay and APC resistance (represented by the ratio (Rs value) of clotting time with and without addition of activated protein C) was observed. Nine out of 14 patients (64%) with poor APC response showed protein S activities below the normal range. Assessment of protein S activity with a second protein S clotting assay using factor Va as substrate confirmed only 47% of the decreased levels of the thromboplastin-based protein S clotting assay.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Course of thrombin activation markers in patients implanted with Palmaz-Schatz stents: first experiences with a post-interventional anticoagulation regimen.
Following implantation of coronary Palmaz-Schatz stents, 29 patients were anticoagulated with a combination of heparin, phenprocoumon and aspirin following a standard protocol. After removing the arterial and venous lines, post-interventional intravenous (i.v.) heparin treatment started with 1500 IU/h for patients > 80 kg and 1250 IU/h for patients < 80 kg. Heparin was monitored by the activated partial thromboplastin time (aPTT) and adjusted by increasing or reducing i.v. heparin by 250 IU/h to maintain the aPTT within the therapeutic range. Phenprocoumon therapy began the day after stent implantation (day 2) and lasted for 3 months. aPTT, Heptest, prothrombin fragment F1 and 2 (F1.2) and thrombin-antithrombin III complexes (TAT) were monitored at standard intervals for 10 days (mean monitoring time: 9.7 +/- 2.3 days). Anticoagulation was efficient with aPTT levels remaining within the therapeutic range on day 9 and the simultaneous, moderate-onset oral anticoagulation within the therapeutic range of the International Normalized Ratio (INR; 2.15-4.80) on day 8 on average, the mean INR being 2.43 +/- 0.76. On day 4, F1.2 levels were significantly higher than on the day of stenting (1.16 +/- 0.30 nmol/l vs 1.04 +/- 0.53 nmol/l; P < 0.005). F1.2 levels fell after day 5, the difference becoming significant from day 8 on (P < 0.05). F1.2 was negatively correlated with the Heptest (P < 0.05) and fell significantly as a function of the INR during phenprocoumon administration (P < 0.001). After phenprocoumon therapy was discontinued over 3 weeks, 25 patients were followed up by angiography. Despite adequate anticoagulation, mean F1.2 levels in patients showing restenosis at follow-up angiography were significantly higher (P < 0.005) than in those without restenosis. In one patient who developed subacute stent thrombosis, clotting factors were determined 20 min before stent occlusion. The levels of F1.2 and TAT were less than all other patients on this day (F1.2: 0.98 nmol/l vs 1.11 +/- 0.40 nmol/l; TAT: 2.7 micrograms/l vs 3.21 +/- 3.38 micrograms/l). Thus, neither F1.2 nor TAT predicted the occurrence of thrombotic stent failure in individuals. Efficient anticoagulation by a combination of anticoagulants is imperative for stent implantation. Using only current routine methods, this way of monitoring anticoagulation is effective for managing combined anticoagulation therapy.
Adult↗