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Biomedical subjects

A Grau

Publications and source records attributed to A Grau.

At least 19 recordsLinked to original sources
PubMed2006

[Chediak-Higashi syndrome].

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive lysosomal disorder characterized by frequent infections, oculocutaneous albinism, high bleeding tendency, and various neurological symptoms. Onset in early childhood mostly leads to lymphohistiocytic infiltration into multiple organs, which is usually lethal without bone marrow transplantation. The adult form of CHS has a milder course, no lymphohistiocytic infiltration, and is characterized by neurological manifestations such as polyneuropathy, parkinsonism, dementia, and ataxia. In young adults, a combination of these defects with oculocutaneous albinism or recurrent infections should bring CHS into consideration. Diagnosis is established by the presence of characteristic eosinophilic peroxidase-positive giant granules in leukocytes. This article summarizes current knowledge about the pathogenesis, clinical course, and therapy of CHS and reports on experience with two adult CHS patients.

Adult↗
PubMed2006

A histological, histochemical and ultrastructural study of the digestive tract of Dentex dentex (Pisces, Sparidae).

Dentex dentex has a short esophagus, a large caecal type stomach, three to six pyloric caeca and a short intestine. Light and electron microscope studies reveal that the esophageal mucosa displays primary and secondary folds, a stratified squamous epithelium with fingerprint-like microridges alternating with a few zones formed by a single layer of columnar cells with apical microvilli. Only primary folds are present in the stomach, which is rich in simple tubular glands, these being absent in the pyloric valve. Two cell types occur in the gastric glands, one with a well developed apical intracytoplasmic membrane system consisting of a vesicular network of smooth membranes, and the other with a supranuclear tubulovesicular system. Pyloric caeca and anterior and posterior intestine mucosae display the same pattern of folding, with primary and secondary folds, without following a definite pattern in their orientation. In the rectum, the folds are oriented longitudinally. Small dense particles containing chylomicrons appear in groups in the intercellular spaces of the caecal and anterior intestinal epithelia. Eosinophilic granular cells (mast cells) appear along the digestive tract mainly within the stratum compactum. Histochemical studies reveal no differences in the composition of goblet cell mucus along the digestive tract. No histochemical differences were detected between enterocytes of the intestine, pyloric caeca and rectum. Neutral mucosubstances dominate in the stomach epithelium and in the goblet cells of the esophagus, pyloric caeca and anterior intestine. Results of the present study are discussed in relation to descriptions of the digestive tract in other sparids.

Animals↗
PubMed2005

Stent-supported angioplasty versus endarterectomy for carotid artery stenosis: evidence from current randomized trials.

BACKGROUND: Carotid artery stenting (CAS) for carotid artery stenoses is evolving as an alternative to carotid endarterectomy (CEA). However, the value of CAS is still a matter of debate. Therefore, we performed a metaanalysis of the randomized controlled clinical trials (RCT) on this issue. METHODS: RCTs were identified through searching MEDLINE, textbooks and by personal communication. RESULTS: Six finished RCTs on this issue could be identified, including 1263 patients, 628 randomized to CAS and 635 to CEA. The 30-day death or stroke rate was 8.0% (50/628) in patients treated with CAS compared to 6.1% (39/635) in CEA patients (OR=1.36, 95% CI: 0.88-2.11; p=0.17; p for heterogeneity=0.009). The rate of cranial nerve palsy was 7.1% in the CEA compared to 0% in the CAS group (p<0.0001). The rate of myocardial infarctions was reduced from 3.1 to 1% (OR=0.32, 95% CI: 0.12- 0.81; p=0.02; p for heterogeneity=0.49). The death or stroke rate during follow-up was 12.1% in patients treated with CAS compared to 12.2% in CEA patients (OR=0.99, 95% CI: 0.70-1.42; p=0.98; p for heterogeneity=0.02). CONCLUSION: The available RCT data on CAS vs. CEA suggest that both methods seem to be equally effective concerning short- and medium-term results, while CAS is associated with lower minor complications than CEA. However, because of the significant heterogeneity between the study outcomes, the results of the large RCTs underway should be awaited before it can be advised to use CAS in a broader perspective.

Angioplasty, Balloon↗
PubMed2005

Absolute temperature, temperature changes and stroke risk: a case-crossover study.

Studies suggest that there is an association between weather patterns and ischemic stroke risk. Exposure to a sudden decrease in temperature may increase stroke risk through altering blood viscosity and/or by triggering infections. We investigated the association between ischemic stroke risk and change in temperature. We used a case-crossover study design with 303 consecutive patients admitted to Heidelberg University, Department of Neurology over a one and a half year period (Aug 1998-Jan 2000). We used one day before stroke as the hazard (case) period matched to two control periods 2-7 days before and after stroke onset and took both ambient maximum temperature and the 24-hour difference in maximum temperature as exposure. There was no risk associated with ambient maximum temperature at all lag times and in all subgroup analyses. For the 24-hour difference, large changes in temperature (>5 degrees C) were associated with an increased risk of acute ischemic stroke regardless of whether the change was negative or positive. The odds ratio for temperature increases >5 degrees C compared to no change in temperature was 2.0 (95% confidence interval (CI): 0.7-5.9) at a lag time of 3 days. We found no relevant relation between temperature and stroke risk. The results suggest that the risk of ischemic stroke may increase with large day-to-day variations upwards or downwards in temperature.

Adolescent↗
PubMed2004

[Superficial siderosis of the CNS. 2 cases and a review of the literature].

Superficial siderosis of the CNS is a rare disease. The superficial deposition of haemosiderin in the cerebrum, cerebellum and spinal cord is due to chronic and recurrent subarachnoidal haemorrhage (SAH). Known sources of bleeding are vascular CNS-tumours, CSF-cavity lesions, vascular malformations, nerve root lesions and neurosurgical interventions. Detection of the source of bleeding is successful in only about 50% of cases. The clinical syndrome is characterized by sensorineural deafness, cerebellar ataxia and pyramidal signs. CSF-investigation might be indicative for SAH, while ferritin and ionic iron can be elevated in the CSF. CT is unspecific and insensitive but MR imaging of the brain and spinal cord is very sensitive and specific. The elimination of the source of bleeding alone might prevent the progression of the disease, therefore, an early and extensive search for this source is highly recommended.

Central Nervous System Diseases↗
PubMed2003

A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young.

BACKGROUND AND PURPOSE: The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke. METHODS: We performed a case-control study including 200 patients with cerebral ischemia aged < or =50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma (antigen) levels. RESULTS: In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; P=0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; P=0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels (P=0.0032; Spearman correlation coefficient rs=-0.48). CONCLUSIONS: The A allele of an intron F polymorphism of the PZ gene appears to be a novel protective genetic marker for the risk of cerebral ischemia in young adults. In the context of juvenile stroke, high PZ plasma levels may represent a prothrombotic condition.

Adult↗
PubMed2003

Prothrombin G20210A mutation, but not factor V Leiden, is a risk factor in patients with persistent foramen ovale and otherwise unexplained cerebral ischemia.

BACKGROUND: Paradoxical embolism via persistent foramen ovale (PFO) is suspected to be a frequent cause of stroke in younger patients. We investigated whether the prevalence of the risk factors for venous thrombosis factor V Leiden (FVL) and prothrombin G20210A mutation (PT G20210A) is increased in this group of patients. METHODS: We examined FVL and PT G20210A mutation in 220 patients (group 1) with cerebral ischemia associated with a PFO and without other etiology, in 196 patients with cerebral ischemia of an etiology other than PFO (group 2), and in 362 healthy subjects (group 3) from the same region in Germany. RESULTS: Heterozygosity for the PT G20210A mutation was more common in group 1 (5.0%) than in group 3 (1.4%; sex- and age-adjusted odds ratio 3.66; 95% CI 1.25-10.75; p = 0.01). By contrast, the mutation was not more common in group 2 (2.6%; odds ratio 1.50; 95% CI 0.42-5.41; p = 0.5). Prevalences of FVL were not different between groups. CONCLUSIONS: We identified PT G20210A but not FVL - the strongest genetic risk factor for deep venous thrombosis - to be significantly associated with stroke attributed to PFO. These findings rise doubts about the concept of paradoxical brain embolism as the dominating mechanism in stroke associated with PFO.

Adult↗
PubMed2002

Sequence analysis of the COL5A2 gene in patients with spontaneous cervical artery dissections.

The authors searched for mutations in the gene that codes for the alpha2 chain of type V procollagen in 10 patients with spontaneous cervical artery dissections (sCAD). Two patients carried a missense mutation affecting the predicted C-propeptide (T1227S; D1429V). A third patient carried two mutations (V509A and P830L) in the same alpha2(V) chain. The T1227S mutation and the V509A/P830L haplotype also were detected among 50 healthy subjects. The D1429V substitution was detected neither in a series of 150 healthy control subjects nor among 50 additional patients with sCAD.

Amino Acid Sequence↗
PubMed2002

[Hereditary amyloidoses associated with transthyretin mutations].

Hereditary amyloidoses form a clinically and genetically heterogeneous group of autosomal-dominantly inherited diseases characterized by the ubiquitous extracellular deposit of fibrillary aggregated proteins. Main components of these unsolvable deposits are physiologic proteins that became amyloidogenic through genetically determined conformation changes resulting in an increase in beta-sheet structures. In the vast majority of cases, the offending protein is variant transthyretin (TTR), of which over 80 mutations are known. Among these, substitution of valine by methionine in position 30 (TTR-Met30) is the most commonly encountered. In typical cases, TTR amyloidoses present with polyneuropathy, carpal tunnel syndrome, autonomic insufficiency, cardiomyopathy, and gastrointestinal features, occasionally accompanied by vitreous opacities and renal insufficiency. Rarely, involvement of the leptomeningeal or meningovascular structures dominates the clinical picture. The clinical expression is highly variable, with many atypical manifestations. Asymptomatic mutations have recently been identified. The age of onset varies greatly between early adulthood and old age. Late-onset atypical manifestations and occurrence of asymptomatic carriers render identification of affected family members difficult despite autosomal-dominant inheritance. Orthotopic liver transplantation (OLT) is the only effective therapy available today. This OLT stops progression of the disease, which is otherwise invariably fatal, by removal of the main production site of the amyloidogenic protein. However, cardiac involvement may progress after OLT for unknown reasons. The indication for OLT and its success depend on the grade of cardiovascular and autonomic dysfunction at the time of surgery, age, comorbidity, and type of mutation. Alternative treatment modalities with drugs stabilizing the native tetrameric conformation of TTR, inhibiting fibril formation or breaking beta-sheet structures, are currently being intensively studied.

Amyloid Neuropathies, Familial↗
PubMed2002

Lipopolysaccharide receptor CD14 polymorphism and risk of stroke in a South-German population.

BACKGROUND: The monocyte receptor for bacterial lipopolysaccharide CD14 is an important mediator of the inflammatory response. Recently, a polymorphism in the promotor of the CD14 gene, C (-260) T, was detected as a risk factor for coronary heart disease. OBJECTIVE: We tested the hypotheses that this polymorphism is a risk factor 1. for cerebral ischemia in general and 2. for cerebral ischemia due to large artery atherosclerosis or microangiopathy in particular. PATIENTS AND METHODS: We performed a case control study including 151 consecutive patients with acute cerebral ischemia treated at our university hospital and 149 control subjects. All control subjects were randomly selected from the general population of the same region in South-West Germany. Genotype frequencies of the C(-260) T polymorphism in the promotor of the CD14 gene were examined by restriction length analysis. RESULTS: The TT-genotype was not associated with cerebral ischemia in general either in univariate or in multivariate analysis together with classical vascular risk factors (odds ratio in multivariate analysis: 1.11; 95 %CI, 0.63 to 1.95). In 70 patients with cerebral ischemia due to atherosclerosis of large arteries or microangiopathy, there was a significantly higher prevalence of the TT-genotype than into control subjects (38.6 % vs. 23.5 %; odds ratio in multivariate analysis 2.26; 95 %CI, 1.13 to 4.54). CONCLUSIONS: We demonstrated that the TT-genotype of the CD14 C(-260) T polymorphism in a South-German population is not associated with an increased risk of cerebral ischemia in general. However, we found that the TT-genotype is associated with a risk of atherosclerotic or microangiopathic stroke. This finding requires confirmation by future studies in larger populations.

Aged↗
PubMed2001

Pathogenesis of cervical artery dissections: association with connective tissue abnormalities.

BACKGROUND: The etiology of spontaneous cervical artery dissection (CAD) is largely unknown. An underlying connective tissue disorder has often been postulated. OBJECTIVE: To further assess the association of CAD with ultrastructural abnormalities of the dermal connective tissue. METHODS: In a multicenter study, skin biopsies of 65 patients with proven nontraumatic CAD and 10 control subjects were evaluated. The ultrastructural morphology of the dermal connective tissue components was assessed by transmission electron microscopy. RESULTS: Only three patients (5%) had clinical manifestations of skin, joint, or skeletal abnormalities. Ultrastructural aberrations were seen in 36 of 65 patients (55%), consisting of the regular occurrence of composite fibrils within collagen bundles that in some cases resembled the aberrations found in Ehlers-Danlos syndrome type II or III and elastic fiber abnormalities with minicalcifications and fragmentation. A grading scale according to the severity of the findings is introduced. Intraindividual variability over time was excluded by a second biopsy of the skin in eight patients with pronounced aberrations. Recurrent CAD correlated with connective tissue aberrations. In addition, similar connective tissue abnormalities were detected in four first-degree relatives with familial CAD. CONCLUSION: CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

Adult↗
PubMed2001

Transthyretin-associated neuropathic amyloidosis. Pathogenesis and treatment.

Hereditary amyloidoses form a clinically and genetically heterogeneous group of autosomal dominantly inherited diseases characterized by the deposit of insoluble protein fibrils in the extracellular matrix. They typically present with polyneuropathy, carpal tunnel syndrome, autonomic insufficiency, and cardiomyopathy and gastrointestinal features, occasionally accompanied by vitreous opacities and renal insufficiency. Other phenotypes are characterized by nephropathy, gastric ulcers, cranial nerve dysfunction, and corneal lattice dystrophy. Rarely, involvement of the leptomeningeal or cerebral structures dominates the clinical picture. The age at onset is as early as 17 and as late as 78 years. The basic constituents of amyloid fibers are physiologic proteins that have become amyloidogenic through genetically determined conformation changes. Mutated transthyretin (TTR), formerly termed prealbumin, is the most frequent offender in hereditary amyloidosis. Orthotopic liver transplantation (OLT) stops the progression of the disease, which is otherwise invariably fatal, by removing the main production site of amyloidogenic protein. The indications for OLT and its success depend on the grade of cardiovascular and autonomic dysfunction at the time of surgery, age, comorbidity, and type of mutation. Alternative treatment modalities with drugs stabilizing the native tetrameric conformation of TTR and inhibiting fibril formation are currently being studied.

Age of Onset↗
PubMed2001

Vitamins C and E attenuate plasminogen activator inhibitor-1 (PAI-1) expression in a hypercholesterolemic porcine model of angioplasty.

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal formation in the arterial wall contributing to restenosis after vascular injury. Antioxidants have been proposed as inhibiting multiple proatherogenic events. We explore the effect of vitamins C and E on PAI-1 expression in an experimental model of angioplasty in hypercholesterolemic pigs. METHODS AND RESULTS: A total of 44 Yucatan minipigs were divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC), and a high-cholesterol plus vitamins C+E (HCV) group. Balloon injury was induced in the right internal iliac artery 4 weeks after initiation of either dietary regimen, and plasma and tissue samples were taken at different time periods to measure PAI-1 activity and vascular inhibitor expression. The cholesterol-rich diet induced an increased in vascular PAI-1 expression in the intima, media and adventitia which was markedly reduced in the HCV group. After injury, severe structural changes were observed in NC and HC animals associated with increased systemic PAI-1 activity (P<0.001) and local PAI-1 expression being more intense in HC group. Vitamins C and E significantly reduced plasma PAI-1 activity (P=0.018) and attenuated the inhibitor expression as compared with HC. CONCLUSIONS: This experimental study in a porcine model of hypercholesterolemia demonstrates that vitamins C and E reduce local and systemic PAI-1 induced after angioplasty as well as the hypercholesterolemia-induced vascular PAI-1.

Analysis of Variance↗
PubMed2001

Aggregational behavior of aqueous dispersions of the antifungal lipopeptide iturin A.

Iturin A, a lipopeptide isolated from Bacillus subtilis, possesses a strong antifungal activity, and has been devoted to a great deal of attention. Since iturin is an amphiphilic compound with a great propensity to self-associate in solution as well as inside the membrane, the question arises to whether its aggregational behavior is dependent on the concentration of the lipopeptide. In order to test this, the ability of iturin suspensions to encapsulate water-soluble molecules has been examined. Iturin was dispersed at different concentrations above its critical micellar concentration, in a buffer containing the water-soluble dye 5,6-carboxyfluorescein. For iturin A micelles, a Stokes radius of 1.3 nm and an aggregational number of 7 was obtained. The results shown in this work clearly demonstrate that iturin dispersions in water, at concentrations of 0.7, 1.4 and 3 mM, i.e. far above the critical micellar concentration (40 microM), are capable of encapsulating carboxyfluorescein, probably by adopting a type of aggregate different from the micelle. Negative-staining electron microscopy shows the presence of vesicles with an average size of 150 nm. By using (14)C-iturin, it is shown that, at 3 mM concentration, 40 % of the iturin molecules adopt this vesicular state. It is proposed that iturin molecules form a fully interdigitated bilayer, where each hydrocarbon tail span the entire hydrocarbon width of the bilayer, resulting in multilamellar vesicles capable of encapsulating an aqueous compartment. The possible implications of these results to the membrane destabilizing effect of iturin A, are discussed according to the dynamic cone-shape of the iturin molecule.

Anti-Bacterial Agents↗
PubMed2001

Hypoglycemic effect of the water extract of Smallantus sonchifolius (yacon) leaves in normal and diabetic rats.

The hypoglycemic effect of the water extract of the leaves of Smallantus sonchifolius (yacon) was examined in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Ten-percent yacon decoction produced a significant decrease in plasma glucose levels in normal rats when administered by intraperitoneal injection or gastric tube. In a glucose tolerance test, a single administration of 10% yacon decoction lowered the plasma glucose levels in normal rats. In contrast, a single oral or intraperitoneal administration of yacon decoction produced no effect on the plasma glucose levels of STZ-induced diabetic rats. However, the administration of 2% yacon tea ad libitum instead of water for 30 days produced a significant hypoglycemic effect on STZ-induced diabetic rats. After 30 days of tea administration, diabetic rats showed improved body (plasma glucose, plasma insulin levels, body weight) and renal parameters (kidney weight, kidney to body weight ratio, creatinine clearance, urinary albumin excretion) in comparison with the diabetic controls. Our results suggest that yacon water extract produces an increase in plasma insulin concentration.

Albuminuria↗
PubMed2001

Oxidative stability of dark chicken meat through frozen storage: influence of dietary fat and alpha-tocopherol and ascorbic acid supplementation.

We used factorial design to ascertain the influence of dietary fat source (linseed, sunflower and oxidized sunflower oils, and beef tallow) and the dietary supplementation with alpha-tocopheryl acetate (alpha-TA) (225 mg/kg of feed) and ascorbic acid (AA) (110 mg/kg) on dark chicken meat oxidation (lipid hydroperoxide and TBA values and cholesterol oxidation product content). alpha-TA greatly protected ground and vacuum-packaged raw or cooked meat from fatty acid and cholesterol oxidation after 0, 3.5, or 7 mo of storage at -20 C. In contrast, AA provided no protection, and no synergism between alpha-TA and AA was observed. Polyunsaturated fatty acid-enriched diets (those containing linseed, sunflower, or oxidized sunflower oils) increased meat susceptibility to oxidation. Cooking always involved more oxidation, especially in samples from linseed oil diets. The values of all the oxidative parameters showed a highly significant negative correlation with the alpha-tocopherol content of meat.

Animal Feed↗
PubMed2001

Influence of dietary fat source, alpha-tocopherol, and ascorbic acid supplementation on sensory quality of dark chicken meat.

We studied the influence of dietary fat source and dl-alpha-tocopheryl acetate and ascorbic acid supplementation on the sensory quality of cooked dark chicken meat stored at -20 C for different periods. Results showed that dietary fat source and alpha-tocopheryl acetate supplementation influenced sensory scores (rancid flavor and aroma and acceptability). Ascorbic acid had no influence on these scores. Thiobarbituric acid values showed a high correlation with sensory scores. In addition, the low levels of alpha-tocopheryl acetate contained in the trace mineral-vitamin mix (20 IU/kg of feed) were enough to prevent rancidity development in cooked dark chicken meat when broilers were fed a saturated fat diet and samples were vacuum-packed and stored at -20 C for 13 mo.

Adult↗