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Biomedical subjects

Martin Stern

Publications and source records attributed to Martin Stern.

15 recordsLinked to original sources
PubMed2006

Influence of donor/recipient sex matching on outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia.

BACKGROUND: Increased risk of transplant related mortality in male recipients of female hematopoietic stem cell grafts and in vitro reactivity of lymphocytes against H-Y encoded gene products in females with rejected male grafts have been documented. An increased rejection of male grafts in female recipients is not reported for solid organ or stem cell transplants and the role of H-Y as transplantation antigen has been controversial. METHODS: Data from 1481 patients with a hematopoietic stem cell transplant for aplastic anemia reported from 154 centers in 28 countries were analyzed. Outcome was compared between patients with donors of the same or opposite sex. RESULTS: Survival at 5 years was significantly better in patients with donors from the same sex: 68% vs. 60% (P = 0.001). Male patients with female donors had a decreased survival (relative risk of death 1.52, P < 0.001) and an increased risk of severe graft-versus-host disease (relative risk 1.33, P = 0.03) compared to recipients of sex-matched grafts. Female patients with male donors had a decreased survival (relative risk of death 1.44, P = 0.01) and an increased risk of rejection (relative risk 2.20, P = 0.01) compared to recipients of sex-matched grafts. In a subgroup analysis, the negative effects of donor/recipient sex-mismatching appeared confined to patients receiving conditioning regimens not containing antithymocyte globulin. CONCLUSIONS: These data confirm H-Y as a clinically relevant transplantation antigen, in both the graft-versus-host and the host-versus-graft direction. Wherever possible, donor-recipient sex-matching should be integrated into donor selection algorithms.

Adolescent↗
PubMed2006

Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children.

Recombinant human deoxyribonuclease I (dornase alfa) is currently used as an inhaled mucoactive agent in the treatment of cystic fibrosis. In a randomized, placebo-controlled, double-blind clinical study in 100 infants, we investigated whether the therapeutic use of dornase alfa can be extended to ventilated, fluid-restricted children to reduce reintubation rate, ventilation duration, pediatric intensive care unit (PICU) stay, and ventilation complications. While reintubation rates were similar for dornase alfa 7% vs. placebo 9% (odds ratio, 0.77; confidence interval, 0.11-4.9), the incidence of atelectasis (6 vs. 17, respectively; P-value 0.051), median ventilation time (2.2 vs. 3.4 days, respectively; P-value 0.043), median length of PICU stay (7 vs. 8 days, respectively; P-value 0.051), and mean costs (4,830 vs. 6,320, respectively) were lower in the dornase alfa group. No adverse effects were observed, even in critically ill patients. We found that dornase alfa was beneficial and safe. Our findings also indicate that dornase alfa is possibly of value from the first day of mechanical ventilation onward, particularly when longer ventilation (>3 days) is expected in fluid-restricted children after cardiac surgery.

Administration, Inhalation↗
PubMed2006

Human leukocyte antigen DR15 is associated with reduced relapse rate and improved survival after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation.

Human leukocyte antigen (HLA) DR15 is associated with autoimmune cytopenia in patients with aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Presence of this antigen also predicts response to immunosuppressive treatment. If DR15 expression on hematopoietic cells also favors induction of immune responses in an allogeneic setting, a lower relapse rate after hematopoietic stem cell transplantation (HSCT) might result through an enhanced graft-versus-leukemia effect. We retrospectively analyzed outcome of HLA-identical sibling HSCT in 192 consecutive patients with acute or chronic leukemia or non-Hodgkin lymphoma. Patients carrying the DR15 antigen had a higher estimated 5-year overall survival (76%) than did DR15-negative patients (55%; P = .04). Improved survival for DR15 patients was due to a significant decrease in death from relapse (5% for DR15(+) versus 24% for DR15(-); P = .02), whereas no difference was seen for rates of transplant-related mortality (19% and 21%, respectively; P = .76). Findings were confirmed by multivariate analyses. Our results show an association of DR15 with a decreased risk of disease relapse and improved survival after HSCT for leukemia or non-Hodgkin lymphoma. This adds to the growing list of links between DR15 and immune reactions in hematopoiesis.

Cohort Studies↗
PubMed2005

Can changes in hydrophobicity increase the bioavailability of alpha-tocopherol?

BACKGROUND: Bioavailability of fat-soluble vitamins from conventional oral supplements is insufficient in some conditions in which fat digestion and absorption are chronically impaired (e. g. cystic fibrosis). AIM OF THE STUDY: We used a water-soluble form of fatsoluble vitamin E (AQUANOVA solubilisate) to create a nutritional supplement (NS) in the form of vitaminized gummi bears (with micellised water-soluble alpha-tocopheryl acetate (100 IU) and 400 mg crystalline vitamin C). We assessed the bioavailability of the NS in comparison to conventional preparations. METHODS: The trial consisted of three study days (d0: NS sucked; d10: NS swallowed; d20: reference products swallowed). A total of 14 subjects (6 male/8 female), aged 25.3 (22.7-35.3) years, BMI 24.3 (19.0-31.7) kg/m(2) participated in the study. They had blood samples drawn after fasting for >or=12 hours and then 1, 5, 15, 30, 60, 120, 180, 240, 300 and 320 minutes after ingesting the vitamins. HPLC and a colorimetric method were used to determine vitamin E and vitamin C, respectively. Areas under the curve (AUC(0-320min)) and maximum increases in plasma concentrations (Delta concentration) were calculated to assess bioavailability. RESULTS: The AUCs(0-320min) of alpha-tocopherol from d0 were significantly larger (p = 0.016) when compared to d20. Moreover, the maximum increase in alpha-tocopherol plasma concentrations was significantly higher for d0 (p = 0.023) and d10 (p = 0.002) when compared to d20. CONCLUSIONS: Short-term bioavailability of AQUANOVA micellised fat-soluble vitamin E from our NS was significantly higher than from regular supplements. The NS will now be tested for its clinical efficacy in a randomized double-blind controlled intervention trial with CF patients.

Adult↗
PubMed2005

Relapsing pancreatitis due to a novel compound heterozygosity in the CFTR gene involving the second most common mutation in central and eastern Europe [CFTRdele2,3(21 kb)].

A 43-year-old otherwise healthy female patient presented with mild pancreatitis. Her family history revealed that her only son had cystic fibrosis. Genotyping of the patient demonstrated CFTR compound heterozygosity CFTRdele2,3(21 kb) and R117H and wild type alleles of the poly-T-tract in intron 8 (7T/7T). No mutations were detected in the cationic pancreatic trypsinogen (PRSS1) and the pancreatic secretory trypsinogen inhibitor (SPINK1) genes. CFTRdele2,3(21 kb) has only been described in 2000 and is the second most frequent severe CFTR mutation after DeltaF508 in central and eastern Europe. This haplotype should be included in the genetic panel when evaluating patients of central or eastern European genetic background for possible CFTR related pancreatitis.

Adult↗
PubMed2005

A major step towards a practical and meaningful gluten analysis.

Coeliac disease is triggered by the cereal protein gluten. Elimination of gluten is the effective therapy. To increase food safety for coeliac patients, gluten has been included in food regulations introducing obligatory labelling. These regulations depend upon effective analytical control. A combined system using cocktail extraction and the R5 enzyme-linked immunosorbent assay has now been described for gluten analysis, which shows good performance. Every effort should be made to keep the diet of coeliac patients as gluten-free as possible.

Celiac Disease↗
PubMed2004

Serologic assay based on gliadin-related nonapeptides as a highly sensitive and specific diagnostic aid in celiac disease.

BACKGROUND: Celiac disease (CD) is induced by wheat gliadins and related cereal proteins. Anti-gliadin antibodies (AGAs) are present in the serum of CD patients, but these antibodies have lower diagnostic specificity and sensitivity than autoantibodies [anti-endomysium antibodies (AEmAs) and anti-tissue transglutaminase antibodies (AtTGAs)]. Recently, AGAs from CD patients were found to recognize deamidated gliadin peptides, probably formed by the action of tissue transglutaminase. METHODS: We synthesized several gliadin peptides and their glutamine-glutamic acid-substituted counterparts on cellulose membranes and tested their recognition by IgA in sera of 52 AEmA-positive CD patients and 76 AEmA-negative controls in a luminescence assay. For comparison, we assayed IgA concentrations of AGAs, AtTGAs, and AEmAs. For measurement of AtTGAs, we used the human recombinant antigen. RESULTS: We identified several nonapeptides that were detected with high specificity by IgA in CD patients. Diagnostic accuracy of the peptide antibody assay was highest when peptide PLQPEQPFP was used in combination with peptide PEQLPQFEE within one assay. AGAs were above the cutoff in 14 of the controls, but only 5 of the controls were positive for peptide antibodies. For comparison, 82% and 94% of samples were correctly classified by AGAs and the combination nonapeptide assay, respectively (P = 0.007), and the AtTGAs correctly classified 98%. CONCLUSION: The peptide antibody assay has higher diagnostic accuracy than AGAs for distinguishing patients with CD from controls, and has diagnostic accuracy similar to that of AtTGAs.

Adolescent↗
PubMed2004

Antioxidant deficiency in cystic fibrosis: when is the right time to take action?

BACKGROUND: Little is known about age- and disease-related changes in prooxidant and antioxidant systems in patients with cystic fibrosis (CF). OBJECTIVE: We investigated changes in antioxidant concentrations and oxidative stress in plasma, buccal mucosal cells (BMCs), and breath condensate in patients with CF in relation to age and disease progression. DESIGN: We recruited 22 patients with CF as well as 35 healthy control subjects and conducted a cross-sectional study by dividing the participants into 4 age groups (<6 y, 6-11 y, 12-17 y, > or =18 y). We collected fasting blood samples, BMCs, and breath condensate. Carotenoids, alpha-tocopherol, vitamin C, protein carbonyls, thiobarbituric acid-reactive substances, and F(2)alpha-isoprostane were assessed. RESULTS: In patients with CF, plasma vitamin C concentrations, plasma and BMC alpha-tocopherol concentrations, and forced expiratory volume in 1 s (percentage predicted) decreased significantly with age. Plasma beta-carotene, beta-cryptoxanthin, and total lycopene were significantly lower in patients than in control subjects in all age groups. Furthermore, alpha-tocopherol and vitamin C plasma concentrations as well as alpha-tocopherol concentrations in BMCs were significantly lower in CF patients > or =18 y old, whereas all indicators of oxidative stress assessed were significantly higher than those same indicators in control subjects. CONCLUSIONS: Adult patients with CF in particular showed distinct vitamin deficits and elevated indicators of oxidative stress in plasma, BMCs, and breath condensate along with a progression of clinical status. We suggest that early in life dietary habits should be improved and that innovative supplementation strategies should be applied to optimize the antioxidant status of patients with CF.

Adolescent↗
PubMed2003

Effect of inherent epileptic seizures on brain injury after transient cerebral ischemia in Mongolian gerbils.

Subthreshold excitotoxic stimuli such as brief cerebral ischemia or chemically induced seizures modulate brain injury resulting from subsequent transient ischemia. Depending on the delay between the two insults, either tolerance or cumulative damage will develop. We were interested whether non-chemically induced inherent epileptic seizures as they occur in Mongolian gerbils have an effect on the outcome of a transient global ischemia, i.e., whether they are an interfering variable in ischemia experiments. Occurrence of spontaneous seizures in adult male gerbils was registered with a video-controlled seizure monitoring system. Bilateral occlusion of common carotid arteries was carried out 2 h or 24 h after the last generalized seizure. After 4 days survival, the extent of ischemia-induced neuronal damage and glial activation were assessed in the hippocampus and striatum. No significant difference in the ischemia induced nerve cell loss was observed in cresyl violet stained sections between the 2-h or 24-h interval gerbils. Neuronal expression of endothelial nitric oxide synthase in CA1 disappeared with neuronal degeneration. Distribution and degree of upregulation of glial fibrillary acidic protein as marker for astrocytes did not differ between the two groups. We concluded that non-chemically induced inherent epileptic seizures neither protect the gerbil brain from injury nor augment the degree of damage resulting from transient forebrain ischemia. Thus, inherent epileptic seizures do not influence the outcome of the insult, making the gerbil a reliable model for studies on transient brain ischemia.

Animals↗
PubMed2003

How gluten-free is gluten-free, and what does this mean to coeliac patients?

A gluten-free diet is the cornerstone treatment of coeliac disease. Until now, it is not known conclusively whether trace amounts of gluten might be allowed in the diet, as suggested by Codex Alimentarius. Gluten-free foods intended for dietary use can now be analysed reliably for residual gluten by the new R5 enzyme-linked immunosorbent assay (ELISA) system. Some major problems of gluten analysis (sensitivity, specificity, reproducibility) can be solved by the new method. Therefore, the information given by the new test system is relevant and superior to earlier methods. Further clinical studies using small dose challenges and dietary records including gluten analysis are necessary until a more meaningful discussion on standards for gluten-free foods can be started.

Celiac Disease↗
PubMed2002

Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers.

Juvenile polyposis syndrome (JPS) is an autosomal dominant predisposition to multiple juvenile polyps in the gastrointestinal tract. Germline mutations in the MADH4 or BMPR1A genes have been found to be causative of the disease in a subset of JPS patients. So far, no genotype-phenotype correlation has been reported. We examined 29 patients with the clinical diagnosis of JPS for germline mutations in the MADH4 or BMPR1A genes and identified MADH4 mutations in seven (24%) and BMPR1A mutations in five patients (17%). A remarkable prevalence of massive gastric polyposis was observed in patients with MADH4 mutations when compared with patients with BMPR1A mutations or without identified mutations. This is the first genotype-phenotype correlation observed in JPS.

Adolescent↗
PubMed2002

Production of recombinant human tissue transglutaminase using the baculovirus expression system, and its application for serological diagnosis of coeliac disease.

BACKGROUND AND OBJECTIVES: Tissue transglutaminase was identified as the main autoantigen in coeliac disease (CD) but enzyme immunoassays applying the commercially available antigen from guinea pig liver show insufficient specificity and sensitivity for diagnosis as compared with endomysium antibodies (EmA). The aim of this present study was to develop a new method for the cloning and expression of human tissue transglutaminase (hu-tTG) and to test hu-tTG in the serological diagnosis of CD. METHODS: Hu-tTG was cloned and expressed using a baculovirus system and SF9 insect cells. The enzyme carried a C-terminal His tag allowing efficient affinity purification from cell lysates. The recognition of hu-tTG by human sera was checked by using an enzyme linked immunosorbent assay (ELISA). For this, 35 patients with active CD were compared with 144 controls (18 patients with bioptically excluded CD, 89 blood donors, 30 patients with inflammatory bowel disease, and seven patients with cystic fibrosis). RESULTS: The ELISA using hu-tTG showed a sensitivity of 100% and a specificity of 98.6%. Titres of antibodies against hu-tTG (anti-hu-tTG) were positively correlated with EmA titres. All results negative for EmA were also negative for anti-hu-tTG. There were, however, EmA positive results up to a titre of 1 : 80 below the cut-off for anti-hu-tTG. For comparison, antibodies against guinea pig tissue transglutaminase (anti-gp-tTG) were determined in parallel. All patients with anti-hu-tTG below the cut-off were also negative for anti-gp-tTG. However, there were eight patients positive for anti-hu-tTG but negative for anti-gp-tTG. CONCLUSIONS: The new test reaches and even exceeds diagnostic efficiency of EmA for coeliac diagnosis.

Adolescent↗
PubMed2002

Ultrasonographic findings correspond to clinical, endoscopic, and histologic findings in inflammatory bowel disease and other enterocolitides.

OBJECTIVE: To compare results obtained by abdominal ultrasonography with clinical findings, including endoscopic and histologic findings, to evaluate the location and activity of inflammatory bowel disease, including disease controls in children. METHODS: Ninety-two ultrasonographic scans and 41 colonoscopic examinations with biopsies were performed in 78 patients (1 month to 17.8 years of age) with Crohn's disease (n = 26), ulcerative colitis (n = 21), inflammatory bowel disease of indeterminate type (n = 2), and disease controls (other intestinal disorders, including infectious and ischemic lesions; n = 29). Laboratory parameters for inflammatory bowel disease were determined, and disease activity was assessed by a combination of clinical and laboratory data. Bowel wall thickness and echo texture were recorded in a standardized way by ultrasonography and compared with endoscopic and histologic findings in a segment-by-segment comparison. RESULTS: Sensitivity and specificity of ultrasonography in detecting patients with severe macroscopic lesions depicted on endoscopy were 77% and 83%, respectively. Sensitivity and specificity of ultrasonography in detecting patients with severe histologic inflammation were 75% and 82%. There was a statistically significant correlation between maximal bowel wall thickness and disease activity score (P < .01). CONCLUSIONS: Abdominal ultrasonography may be helpful in evaluating the location, severity, and inflammatory activity of inflammatory bowel disease in children and young adults.

Adolescent↗