Safety of retroviral gene marking with a truncated NGF receptor.
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Biomedical subjects
Publications and source records attributed to M Weber.
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We assessed the effect of rabbit antithymocyte globulin manufactured by Fresenius (ATG-F) on the hemostatic system in patients (n=12) with various hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT) from HLA-matched unrelated donors. For this purpose, we monitored different parameters of coagulation before, during and after the administration of ATG-F. As a control group, we recruited patients (n=10) undergoing HSCT from their HLA-identical siblings who did not receive ATG-F as part of their preparative regimens. At 24 and 48 h after ATG-F treatment had been initiated, we found a temporary rise in D-Dimer, tissue factor, soluble thrombomodulin and thrombin-antithrombin III complex levels and a significant decrease of platelet counts in patients treated with ATG-F as compared to the control group. No differences between the two groups could be detected with regard to global coagulation tests as well as the incidence of bleeding manifestations, thromboembolic complications or the development of vascular-occlusive-disease of the liver. This temporary state of a stressed but compensated coagulation system under ATG-F therapy can be addressed as nonovert disseminated intravascular coagulation (DIC). The effect was independent from the different conditioning regimens and eased off after cessation of ATG-F. We conclude that ATG-F can induce nonovert DIC in patients receiving antithymocyte globulin as part of their conditioning regimen for HSCT.
The objectives of the study were (i) to evaluate the effects of age and body size on the apparent digestibility of a dry expanded diet and (ii) to determine whether poor faecal quality could be related to lower nutrient utilization. Four breeds of dogs were used: six Miniature Poodles (MP), six Medium Schnauzers (MS), six Giant Schnauzers (GS) and six Great Danes (GD). Digestive trials were performed at 11, 21, 35 and 60 weeks of age. Faecal moisture and scoring were recorded at the same periods. Digestibility coefficients of all macronutrients increased significantly (p < 0.05) with age in all four breeds. Organic matter digestibility increased from 80.2 +/- 1.5 to 85.5 +/- 1.5% in MP; from 80.2 +/- 0.9 to 86.3 +/- 0.5% in MS; from 79.6 +/- 4.2 to 88.9 +/- 0.5% in GS and from 85.7 +/- 1.5 to 88.4 +/- 0.8% in GD. Crude protein digestibility increased from 74.5 +/- 4.0 to 81.5 +/- 1.9% in MP; from 74.3 +/- 3.9 to 82.6 +/- 0.9% in MS; from 71.8 +/- 6.0 to 85.9 +/- 0.9% in GS and from 80.8 +/- 4.6 to 84.8 +/- 1.3% in GD between 11 and 60 weeks of age, respectively. Mean faecal moisture also increased over the growth, except in GS. Nutrient digestibility was significantly higher in large dogs at all age periods. However, larger dogs showed lower faecal scores and increased faecal moisture. In conclusion, these results show (i) an effect of age and body size on nutrients digestibility and (ii) that the lower faecal quality observed in healthy large breed dogs does not appear related to lower nutrient utilization.
We report four new cases of cerebral venous thrombosis (CVT) occurring in patients with multiple sclerosis (MS). Each patient had undergone lumbar puncture at varying times prior to clinical presentation (4 days to over 1 year). Only two of the patients had received intravenous (i.v.) methylprednisolone 48 h prior to CVT and were under oral contraception, a risk factor for cerebral thrombophlebitis. The other two patients had not undergone recent lumbar puncture, were not taking corticosteroids and did not present vascular risk factors. The patients all had normal routine blood work-ups and none had thrombophilia. All patients dramatically improved with full systemic heparinization. Minor sequelae were noticed in two patients. The pathogenesis underlying the occurrence of CVT in MS patients remains unclear and we discuss the relationship between lumbar puncture, steroid treatment and CVT.
OBJECTIVE: To describe the incidence of pneumococcal bacteremia not associated with infection of the central nervous system, investigate the susceptibility of bacterial isolates to beta-lactams, evaluate risk factors for antibiotic resistance, and determine factors predicting patient outcome. METHODS: Over a period of 1 year, 919 Streptococcus pneumoniae isolates were collected from 919 patients with bacteremia in eight French counties. Their clinical and microbiological features were recorded. Univariate and multivariate analyses were used to determine risk factors for penicillin-non-susceptible pneumococcal bacteremia and predictors of fatal outcome. RESULTS: Of the 919 patients in the study, 27% were infected with penicillin-non-susceptible pneumococci (PNSP): 17.8% of the isolates were intermediate to penicillin, 7.2% were resistant to penicillin, 16% were intermediate to amoxicillin, and 11% were intermediate to cefotaxime; no PNSP were resistant to either of the last two antibiotics. The most common PNSP serotypes isolated were 14 (41%) and 23 (24%). A statistically significant relationship between PNSP infection and age below 5 years or above 60 years in the different counties was observed by univariate and multivariate analysis. Gender, origin of bacteremia, co-morbidity, immunodeficiency, previous hospitalization and nosocomial infection were not predisposing factors associated with PNSP. The mortality rate was 20.6%: there was no increase in mortality among patients with PNSP bacteremia. Age was the strongest risk factor for mortality, but immunodeficiency also seemed to have had an impact on mortality. Clinical outcome was more closely related to clinical conditions than to the susceptibility status of S. pneumoniae. CONCLUSION: Among cases of bacteremia, 27% were caused by PNSP, but this level varies according to the counties and the age of the patients. Infection-related mortality was high, but there was no increase related to penicillin G non-susceptibility of the infecting strain.
A placebo controlled, randomised, parallel group, multicentre trial conducted in accordance with the guidelines of Good Clinical Practice (GCP) shows the efficacy and safety of a standardised extract of fresh berries of Crataegus oxyacantha L. and monogyna Jacq. (Crataegisan) in patients with cardiac failure NYHA class II. A total of 143 patients (72 men, 71 women, mean age of 64.8 (8.0 years) were recruited and treated with 3 times 30 drops of the extract (n = 69) or placebo (n = 74) for 8 weeks. The primary variable for the evaluation of efficacy was the change in exercise tolerance determined with bicycle exercise testing, secondary variables included the blood pressure-heart rate product (BHP). Subjective cardiac symptoms at rest and at higher levels of exertion were assessed by the patient on a categorical rating scale. An overall assessment of efficacy at the final visit was provided by the patient and the investigator. In the ITT population there was a significant increase in exercise tolerance in both groups between visit 1 and visit 3. The difference between the treatment groups was 8.3 watts in favour of the standardised extract of fresh Crataegus berries (p = 0.045). The result is confirmed in the PP population (p = 0.047). Changes in BHP at 50 watts and at comparable maximum load were in favour of Crataegus extract but the results are not statistically significant. The subjective assessment of cardiac symptoms at rest and at higher levels of exertion did not change significantly and the patient and investigator overall assessment of efficacy were similar for the two groups. The medication was well tolerated and had a high level of patient acceptability. The significant improvement, due to the fact that dyspnoea and fatigue do not occur until a significantly higher wattage has been reached in the bicycle exercise testing allows the conclusion that the recruited NYHA II patients may expect an improvement in their heart failure condition under long term therapy with the standardised extract of fresh Crataegus berries.
Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Several antigens have been associated with IPD using serological methods. We systematically analysed HLA class I and II alleles in 45 German Caucasian IPD patients using sequence-specific oligonucleotides and sequence-specific primer technology. Applying Bonferroni adjusted p values, we demonstrate a statistically significant increase of the DQB1*06 allele (p = 0.002) in IPD which may indicate an association between IPD and the immune system. Alternatively, HLA alleles might be in linkage disequilibrium with genes located next to the HLA locus.
There has been limited use of ceramic materials for all-ceramic posterior bridges. Major reasons are the low strength, the strength scatter, and the time-dependent strength decrease of ceramics due to slow crack growth. The objective of this study was to predict the long-term failure probability and loading capability of all-ceramic bridges (Empress 1, Empress 2, In-Ceram Alumina, and ZrO(2)) by computational techniques. The lifetimes of different bridge model designs were predicted by means of the NASA post-processor CARES. Bridges made of zirconia showed a very high mechanical long-term reliability. Empress I and InCeram Alumina seem to be insufficient as posterior bridge materials based on this prediction. The lifetime of the all-ceramic bridges can be significantly increased by improving the design in the connector area. We conclude that computational techniques can help to judge a ceramic material and a specific ceramic bridge design with respect to mechanical reliability before clinical use.
Obstruction of the renal veins may result in proteinuria and is frequently caused by thrombosis or tumorous processes. Since thrombosis and malignancy may occur simultaneously in the venous outflow of the kidneys, search for an underlying intraluminal tumor may be impeded by extensive thrombosis in the lumen of renal and caval veins. We report the case of a 30-year-old man with moderate proteinuria which was caused by an obstructing process of the vena cava inferior and the renal veins. While the obstructive mass was initially misdiagnosed as thrombosis, positron emission tomography helped to reveal the tumorous character of the lesion and fine-needle biopsy allowed rapid diagnosis of a leiomyosarcoma originating from the caval or renal veins. We conclude that undelayed diagnosis of the cause of renal and caval vein obstruction is facilitated by early positron emission tomography and subsequent fine-needle biopsy to identify possible tumorous lesions.
Anomalies of neural tube closing are serious malformations which are encountered most often in babies of epileptic women treated with anti-epileptic drugs during pregnancy. Dietary supplementation of folic acid has been suggested as a preventive measure in these cases, based on the long suspected association between folic acid deficiency and congenital malformations. Folic acid deficiency usually results from insufficient dietary intake, or increased requirements during pregnancy. Moreover, certain anti-epileptic drugs can reduce the availability of folic acid. In secondary prevention, the protective effect of folic acid has been clearly demonstrated, whilst epidemiological data suggest that such treatment is also useful in primary prevention. With respect to women with epilepsy, there is a clear consensus as to the interest of dietary supplementation with folic acid before conception and during the first three months of pregnancy (the period of organogenesis), particularly given the fact that side-effects are extremely rare. Apart from recurrence prevention, where a dose of 4mg/day is recommended, no standard dosing guidelines exist. We would suggest that this same dose be used for epileptic patients in pregnancy, particularly if they are treated with barbamazepine or valproic acid.
The WHO has published guidelines for the inpatient management of severe malnutrition. A qualitative study in hospitals in developing countries is being conducted to document the re-organisation of the clinical ward and support services required to implement these guidelines and to gain an impression of the feasibility and sustainability of such a re-organisation. Following a postal survey of experts in the management of malnutrition in children in developing countries, hospitals were contacted and asked if they were interested to participate in the study. If so, they were requested to submit background information about admission patterns, the frequency of malnutrition, and current practice. Based on this information, hospitals are selected for a preliminary visit. Following this, and the final selection, a paediatrician conducts three visits to the study hospital over a one-year period to appraise the current practice, assist the health staff in recognising the strengths and shortcomings of their current management, help them find locally appropriate solutions, support the implementation process through a participatory approach and assess the outcome. A structured survey instrument is used to guide the assessment and identification of problems. Results of the first visit, which documents the existing situation, and changes identified by staff and implemented during the second visit are presented.
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The role of platelet hyperaggregability as a possible risk factor for venous thromboembolism is not well defined. Some authors described enhanced maximal platelet aggregation in platelet aggregometry as a contributing factor for arterial and venous thrombosis. This syndrome has been termed "sticky-platelet syndrome" (SPS). The diagnosis of SPS is based on the demonstration of platelet hyperaggregability in aggregometry after stimulation with epinephrine (EPI) and/or adenosine diphosphate (ADP). We investigated platelet hyperaggregability in platelet-rich plasma (PRP) of patients (n = 34) with unexplained venous thromboembolism in comparison to healthy individuals (n = 53). For analysis, platelet aggregometry was performed and the influence of epinephrine, adenosine diphosphate, collagen (Coll) and thrombin receptor-activated peptide (TRAP-6) as agonist were determined. Compared to the control group, patients with venous thromboembolism showed an enhanced maximal platelet aggregation with low concentrations of TRAP-6 (2 microM) and collagen (0.05 microM). In contrast, we could not detect an increased platelet aggregation with EPI or ADP. Our results indicate that platelet hyperaggregability may represent an independent risk factor in patients with otherwise unexplained venous thromboembolism. In our study, low concentrations of TRAP-6 and collagen are superior to EPI and ADP to define platelet hyperreactivity in platelet aggregometry.
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BACKGROUND: Certain nonsteroidal anti-inflammatory drugs are effective in the acute treatment of migraine attacks. The authors report a double-blind, placebo-controlled, randomized cross-over trial of a dual-release formulation of oral ketoprofen in the acute treatment of migraine attacks. METHODS: The authors compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to four consecutive attacks in 235 intent-to-treat patients (out of 257 randomized patients) with migraine with or without aura. The principal efficacy outcome was headache relief (reduction in headache severity from severe or moderate to mild or absent at 2 hours). RESULTS: Results are based on 838 attacks with a severe or moderate headache that were evaluable at 2 hours. Relief was reported for 62.6% of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and 66.8% with zolmitriptan. The difference between the three active treatments and placebo (27.8% relief) was highly significant, both tests of ketoprofen vs placebo being globally controlled at a 5% level for the type I error (primary analysis). Headaches at 2 hours disappeared more frequently for the active treatments than for placebo. The authors also demonstrated efficacy on most other secondary outcomes. The tolerance of ketoprofen was good (similar to that of placebo). CONCLUSIONS: Oral ketoprofen (75 mg or 150 mg) in a dual-release formulation is an effective and well-tolerated drug in the acute treatment of migraine attacks.
AIM: The aim of our investigations was to answer the question of whether the radiologic classification according to the investigations of Nasca has prognostic relevance for congenital scoliosis. Based on our results, a therapeutic concept was given. PATIENTS AND METHODS: Radiographs of 49 patients with a congenital scoliosis were classified according to Nasca. The progression of the malformation was analyzed by regarding the changes over a period of 8.3 years on average. RESULTS: Of the analyzed patients with congenital scoliosis, 73% showed a mean progression rate of 1.8 degrees per year. The most advanced progress of the Cobb angle per year was seen in patients with unilateral unsegmented bars with or without additional hemivertebrae (type 4 according to the Nasca classification) and patients with wedge-formed vertebrae (type 2a according to the Nasca classification). The presence of unilateral bars and the location of the hemivertebra or hemivertebrae (type 4) and wedge-formed vertebrae (type 2a) are the major determinants of deformity. Within the scope of our investigations, the following three factors were seen as deleterious when combined: thoracolumbal and long-distance scoliosis, female gender, and prepubertal growth period. CONCLUSION: From our analysis of 49 patients, we can propose the following therapeutic system for congenital scoliosis. Sole treatment with physiotherapy should only be recommended with congenital scoliosis curves ranging from 0 degrees to 20 degrees according to the Cobb method. With a Cobb angle smaller than 40 degrees and some flexibility remaining in the spine, the congenital scoliosis should be treated additionally with corrective casts. For congenital scoliosis with a Cobb angle of more than 50 degrees, as well as for congenital scoliosis with a poor prognosis (for example unilateral bars), a spondylodesis of the spine should be done before reaching the age of 5 years.
UNLABELLED: Sudeck's atrophy: pathophysiology and treatment of a complex pain syndrome. SUMMARY: The "Morbus Sudeck" or Complex Regional Pain Syndrome (CRPS) forms a typical triad of motor, sensory and autonomic symptoms. It is clinically characterized by spontaneous pain and hyperalgesia not limited to a single nerve territory and disproportionate to the inciting event. An underlying pathophysiology which could explain the whole symptomatology of CRPS is still unknown. Therefore, nowadays therapy is still symptomatic. However, recent research led to a better understanding of the disease and to the beginning of a pathophysiologically orientated therapy.