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H Schneider

Publications and source records attributed to H Schneider.

At least 73 records · Page 4Linked to original sources
PubMed2003

Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse chromosome 5.

We hypothesized that upper airway obstruction (UAO) leads to a compensatory increase in the duty cycle [ratio of inspiratory time to respiratory cycle length (Ti/Tt)], which is determined by genetic factors. We examined the compensatory Ti/Tt responses to 1). UAO and hypercapnia among normal individuals and 2). hypercapnia in different inbred strains, C3H/HeJ (C3) and C57BL/6J (B6), and their first- and second-generation (F2) offspring. 3). We then used the compensatory Ti/Tt response in the F2 to determine genetic linkage to the mouse genome. First, normal individuals exhibited a similar increase in the Ti/Tt during periods of hypercapnia (0.11 +/- 0.07) and UAO (0.09 +/- 0.06) compared with unobstructed breathing (P < 0.01). Second, the F2 offspring of C3 and B6 progenitors showed an average Ti/Tt response to 3% CO2 (0.42 +/- 0.005%) that was significantly (P < 0.01) greater than that of the two progenitors. Third, with a peak log of the odds ratio score of 4.4, Ti/Tt responses of F2 offspring are genetically linked to an interval between 58 and 64 centimorgans (cM) on mouse chromosome 5. One gene in the interval, Dagk4 at 57 cM, is polymorphic for C3 and B6 mice. Two other genes, Adrbk2 at 60 cM and Nos1 at 65 cM, have biological plausibility in mechanisms of upper airway patency and chemosensitivity, respectively. In summary, Ti/Tt may serve as an intermediate physiological phenotype for compensatory neuromuscular response mechanisms for maintaining ventilation in the face of UAO and hypoventilation and to help target specific candidate genes that may play a role in the expression of sleep-disordered breathing.

Adult↗
PubMed2003

Importance of early allergen contact for the development of a sustained immunoglobulin E response in a dog model.

BACKGROUND: Immunoglobulin E (IgE)-mediated allergies are postulated to require early allergen contact and sensitization for the full development of sustained IgE levels. METHODS: Thirty-two Beagle dogs from seven litters selectively bred for their high IgE response were sensitized by subcutaneous injection of chicken ovalbumin (OVA), peanut extract and recombinant birch pollen allergen (Bet v 1). In half of the dogs from each litter, sensitization injections were started on the first day of life; the other half of the same litter was first sensitized at the age of 4 months. To evaluate whether early sensitization also predisposes the animals to IgE responses to other allergens later in life, we injected a recombinant timothy grass pollen allergen (Phl p 5) later on, at the age of 10-12 months. Allergen-specific serum IgE and IgG levels were evaluated with enzyme-linked immunosorbent assays. In addition, 21 dogs were challenged with aerosolized OVA to measure bronchoconstrictive changes in lung function. RESULTS: Early sensitized dogs developed significantly higher OVA-specific serum IgE levels than late sensitized dogs, in contrast to the IgG levels, which were lower in these dogs (p < 0.001). The increase in specific serum IgE and IgG following boosting remained different between the two groups for over a year. Titers of specific serum IgE and IgG were also different after sensitization with a new allergen injected later in life for the first time. Dynamic pulmonary compliance and resistance, both parameters for bronchoconstriction induced by OVA aerosol challenge, were also significantly higher in early sensitized dogs (for both parameters, p < 0.01). CONCLUSIONS: Contact with an allergen early in life is decisive for the development of sustained IgE levels and the development of IgE responses to additional allergens encountered later in life. Allergen avoidance during early life may have some preventive effect on IgE-mediated allergy in dogs.

Age Factors↗
PubMed2003

Family representations in relationship episodes of patients with a diagnosis of bulimia nervosa.

The influence of the family on the development and the maintenance of bulimia nervosa can be seen both biologically and psychosocially. Genetic influences are discussed, but their effects do not explain the aetiology exclusively. Clinical observations and research findings support the role of family dynamics, family environment, and family functioning. In particular, a low level of cohesion, a lower degree of expressiveness, and more conflicts seem to characterize the family of patients with a diagnosis of bulimia nervosa. The present study addresses the question of how patients suffering from bulimia differ from other patients in psychotherapy and from non-clinical control subjects in the way they perceive their ongoing and their past family relationships. The Core Conflictual Relationship Theme method is applied to narrative material from patients belonging to these three groups. Results show expected differences between patients and normal control subjects and virtually no differences between the group of patients with a diagnosis of bulimia nervosa and the group of patients with diagnoses different from bulimia.

Adult↗
PubMed2003

Cartilage regeneration by gene therapy.

Damage of articular cartilage is a frequent clinical problem and is commonly considered to be irreversible. Full-thickness defects may lead to the formation of fibrous repair tissue of minor mechanical quality, while partial-thickness lesions hardly show any repair response. Surgical approaches often fail to restore the articular surface, facing the problem of incomplete chondrogenesis or rapid degradation of the repair tissue. However, advances in molecular biology have revealed the potential of growth factors, differentiation factors, and cytokines in directing cellular differentiation and metabolic activity. Anabolic factors including members of the TGF-beta superfamily, IGF-1, FGF, or HGF have proven their potential to stimulate chondrogenesis and synthesis of cartilage-specific matrix components, allowing the formation of a hyaline cartilage-like repair tissue in experimental studies. In addition, anti-catabolic or anti-inflammatory molecules, such as IL-4, IL-10, IL-1Ra, and TNFsR may also exert beneficial effects by inhibiting excessive cartilage degradation. Although it is questionable whether regeneration of hyaline cartilage implying a complete restoration of the articular surface by a tissue that is identical with the original can ever be achieved, all these molecules have been considered as suitable tools for cartilage repair. The transfer of the respective genes into the joint, possibly in combination with the supply of chondroprogenitor cells, might be an elegant method to achieve a sustained delivery of such therapeutic factors at the required location in vivo. This review focuses on the therapeutic molecules, the suitability of different viral and non-viral vectors for intraarticular gene transfer and the lessons learned from gene therapy studies on various animal models.

Adenoviridae↗
PubMed2003

Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results.

INTRODUCTION: Esomeprazole, the first proton pump inhibitor to be developed as an optical isomer, has demonstrated more effective healing vs. omeprazole and lansoprazole in patients with reflux oesophagitis (RO). However, RO recurs in a high proportion (approximately 80%) of these patients within 12 months of initial therapy, highlighting the importance of maintenance treatment. Previous studies have shown esomeprazole to be effective as maintenance therapy in healed RO patients. AIM: This study was conducted to compare esomeprazole 20 mg once daily (o.d.) with lansoprazole 15 mg o.d. for the prevention of recurrence of RO. METHODS: 1391 patients with endoscopically verified RO (LA classification) were enrolled in this randomized, double-blind, parallel-group, multicentre trial. During the initial healing phase of the study, all patients received 4-8 weeks' open treatment with esomeprazole 40 mg: 1236 healed (identified by endoscopy at 4 and 8 weeks) and symptom-free (i.e. no heartburn or acid regurgitation) patients were randomized to 6 months' maintenance treatment with esomeprazole 20 mg o.d. or lansoprazole 15 mg o.d. Time to relapse (relapse of RO and/or discontinuation due to symptom recurrence) was analysed using a log-rank test. RESULTS: Esomeprazole maintained a significantly higher proportion of patients in remission than lansoprazole over the 6-month course of treatment (P < 0.0001, intention-to-treat analysis). After 6 months' treatment, 83% of esomeprazole recipients were in remission compared with 74% of lansoprazole recipients (life-table estimates). Esomeprazole gave a longer time to relapse than lansoprazole irrespective of baseline LA Grade, significantly so for baseline LA Grades B, C and D (P < 0.05 for each comparison). Significantly more patients were free from heartburn in the esomeprazole group compared with the lansoprazole group at 1, 3 and 6 months (P < 0.05). Significant differences at 6 months between esomeprazole 20 mg o.d. and lansoprazole 15 mg o.d. were also observed for control of epigastric pain and acid regurgitation (P < 0.05 and P < 0.001, respectively). Both treatment regimens were well tolerated. CONCLUSION: Esomeprazole 20 mg o.d. is a more effective maintenance treatment than lansoprazole 15 mg o.d. for symptom-free patients with healed RO.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

The 2001 Giessen Cohort Study on patients with prostatitis syndrome--an evaluation of inflammatory status and search for microorganisms 10 years after a first analysis.

During the last years tremendous changes have occurred in the epidemiologic knowledge and the diagnostic process of the prostatitis syndrome. A new worldwide-accepted classification system has become the gold standard in contemporary literature. The aim of this study was to compare the inflammatory and infectious status of men with prostatitis syndrome with results from our study cohort from 1992. A total of 168 symptomatic men (mean age 43.2 years; range 18-79) attending the Giessen prostatitis outpatient department were included. All men underwent a standard four-glass-test including leucocyte analysis in all specimens. A routine search for Ureaplasma urealyticum and Chlamydia trachomatis was performed. Ejaculate analysis following World Health Organization (WHO) criteria has been performed including the evaluation of increased number of peroxidase-positive leucocytes (PPL). Men were classified according to the National Institutes of Health (NIH) prostatitis classification. The distribution of patients according to NIH criteria is as follows: NIH II (4.2%), NIH IIIA (31.5%), NIH IIIB (50.0%) and urethroprostatitis (14.3%). Chlamydial infection was present in one man (0.6%). Only two men with increased leucocytes in prostatic secretions demonstrated > or =106 million ml-1 PPL in semen. As compared with our cohort study 10 years ago, the proportion of the different subtypes of the prostatitis syndrome have remained stable. The aetiological spectrum of chronic bacterial prostatitis has not changed whereas, in contrast, the prevalence of C. trachomatis now is found to be strikingly reduced. Using the WHO cutpoints for leucocytospermia the inclusion of seminal leucocytes to the diagnostic process has not influenced the distribution between inflammatory (type NIH IIIA) and noninflammatory (type NIH IIIB) chronic pelvic pain syndrome.

Adult↗
PubMed2002

Physicians' preferences and expectations in stroke rehabilitation--results of a case-based questionnaire survey.

PURPOSE: Analysis of medical decisions in the differential allocation of stroke rehabilitation programmes. METHOD: Medical specialists routinely involved in the treatment and rehabilitation of stroke patients from acute hospitals, rehabilitation centres, and the Medical Services of the Workers' Pension Funds of Sachsen-Anhalt and Mecklenburg-Vorpommern were included in a systematic survey, in which they had to give their opinions on the individually optimal rehabilitation setting and therapies and probable outcome on the basis of case vignettes. These specialists are crucial for decision-making in rehabilitation resource allocation. RESULTS: Both allocation and prognosis did not depend only on patient but also on physician characteristics. Neurologists tended to prefer outpatient rehabilitation and expected a greater effect of rehabilitation upon ADL-function than specialists from other professions. Preferred rehabilitation setting did not influence the physicians' subjective prognosis. For patients who qualified both for in- and outpatient rehabilitation, the two settings, therapeutic potentials were considered to be equivalent. CONCLUSIONS: Differences in setting and treatment preferences between experts concerning optimal treatment cannot be resolved on the basis of available evidence. Further data are required that allow to decide which type of rehabilitation is best suited for a given patient.

Adult↗
PubMed2002

Allergic pulmonary and ocular tissue responses in the absence of serum IgE antibodies (IgE) in an allergic dog model.

Allergen-specific serum IgE may be insensitive as a marker for IgE-mediated reactions at the mucosal level. Five of six atopic beagle dogs developed high ovalbumin (OVA)-specific serum IgE levels after sensitization. This study aimed to show that these dogs still express allergen-specific IgE at the pulmonary and ocular mucosal levels and in the skin even when corresponding serum IgE was below the detection limit. When serum IgE levels were negative, all dogs exhibited allergic reactions at the tissue level. Specifically, they displayed positive ocular reactions after an ocular OVA challenge. After airway challenge with aerosolized OVA, five out of six animals reacted with decreased compliance and increased resistance of the lungs. Furthermore, an eosinophilia in the bronchoalveolar lavage fluid (BALF) was observed. Four weeks after the last exposure to OVA, IgE-positive BALF cells were seen in all animals. Six weeks on, all dogs still displayed positive skin reactions to OVA. This indicates that not only skin testing but also detection of ocular and pulmonary allergic tissue reactions including cell-bound IgE in BALF can serve as more sensitive and lasting surrogate markers of hypersensitivity in the allergic dog model than detection of allergen-specific serum IgE levels.

Animals↗
PubMed2002

Burden of illness imposed by severe sepsis in Germany.

Sepsis is a systemic response to severe infection in critically ill patients and is among the most frequent causes of death in intensive care medicine. Every year between 44,000 and 95,000 persons suffer from this illness in Germany. With the help of a retrospective electronic chart analysis in three adult ICUs of three university hospitals we calculated by a bottom-up approach the direct costs of these patients yielding per patient costs of 23,297 euros on average. Linking the direct costs per patient with the incidence data, the total direct costs for severe sepsis in Germany per year were estimated to range from 1,025 to 2,214 million euros. Direct costs, however, were found to make up only about 28% of the burden of disease of severe sepsis. The indirect costs range between 2,622 and 5,660 million euros. Productivity loss due to premature death does account for the largest part of the indirect costs. In conclusion, severe sepsis imposes annual costs between 3,647 and 7,874 million euros to the German society.

Journal Article↗
PubMed2002

ABO blood groups in the primate species of Cebidae from the Amazon region.

The ABO blood groups were determined in blood and saliva collected from 40 Aotus infulatus, 74 Saimiri sciureus, and 96 Cebus apella from the Amazonian region along the Tocantins river. Saliva samples were tested for human ABH antigens by a standard hemagglutination inhibition test. Aotus infulatus showed monomorphism, exhibiting only the B blood group. Saimiri sciureus exhibited the A (67) and AB (7) phenotypes. All four phenotypes have been found in C. apella: O (8), A (52), B (19) and AB (17). The observed distribution was as expected assuming Hardy-Weinberg equilibrium. The titers of ABH substances varied among the species and phenotypes. The B-like agglutinogen, common to all New World monkey species tested, was detected in the red blood cells. Sera were used to detect naturally occurring antibodies and the results showed discrepancies between serum and saliva phenotypes in all species studied.

ABO Blood-Group System↗
PubMed2002

First-trimester umbilical cord diameter: a novel marker of fetal aneuploidy.

OBJECTIVE: To compare the umbilical cord diameter at 10-14 weeks of gestation of chromosomally normal and abnormal fetuses. METHODS: In a consecutive series of women, who were undergoing routine sonographic evaluation at 10-14 weeks of gestation, umbilical cord diameter and nuchal translucency were measured. Reference ranges for umbilical cord diameter according to gestational age and crown-rump length were constructed. Fetal karyotype was obtained at chorionic villus sampling, amniocentesis or at delivery in newborns with features suspicious for chromosomal abnormalities. RESULTS: During the study period, 784 patients met the inclusion criteria. Of these, a fetal or placental chromosomal abnormality was present in 17 cases. The mean umbilical cord diameter increased with gestational age (r = 0.41, P < 0.001). The proportion of fetuses with an umbilical cord diameter above the 95th centile was higher in the presence of fetal or placental chromosomal abnormalities than in normal fetuses (5/17 vs. 39/767, P < 0.01). Among fetuses with an abnormal fetal or placental karyotype, nuchal translucency was above the 95th centile for gestational age in 10 cases. When only fetal chromosomal abnormalities were considered (n = 14), the combined detection rate was 85.7%(12/14). CONCLUSIONS: Sonographic assessment of the umbilical cord in early gestation appears to identify a subset of fetuses at increased risk of chromosomal abnormalities.

Adult↗
PubMed2002

Importance of sympathetic activation for the expression of Na+-Ca2+ exchanger in end-stage failing human myocardium.

AIMS: In end-stage heart failure, an alteration in the expression of the Na+-Ca2+ exchanger has been reported. Regulation of its expression is largely unknown. We sought to find out whether Na+-Ca2+ exchanger in human heart failure is regulated by sympathetic activation. In addition, since Na+-Ca2+-exchange is electrogenic, we conjectured whether increased expression of Na+-Ca2+ exchanger is associated with an increased incidence of cardiac arrhythmias. METHODS AND RESULTS: Twenty-three patients suffering from end-stage cardiac failure were examined in the hours preceding cardiac transplantation. Plasma levels of norepinephrine, epinephrine, atrial natriuretic peptide, renin activity, aldosterone, tumour necrosis factor (TNF)-alpha, and TNF-receptors were measured. All parameters were elevated relative to 21 healthy control subjects. As determined by immunoblots, protein levels of the Na+-Ca2+ exchanger were increased by 56% and protein levels of sarcoplasmic reticulum (SR) Ca2+-ATPase were decreased by 20% in left ventricles of the explanted failing hearts. A significant correlation between protein and neurohumoral levels was exclusively found for the Na+-Ca2+ exchanger with norepinephrine (r=0.64; P=0.01). Recent Holter ECGs revealed that patients with sustained or non-sustained ventricular tachycardia (more than three consecutive beats) had significantly higher Na+-Ca2+ exchanger protein and plasma norepinephrine levels than patients with a maximum of two consecutive beats (Na+-Ca2+ exchanger: 109+/-10 vs 83+/-7, n=11 each, P<0.05; norepinephrine: 1359+/-159 vs 656+/-88 pg. ml(-1), n=9 each, P<0.001). CONCLUSIONS: Sympathetic activation may enhance the expression of Na+-Ca2+ exchanger in end-stage heart failure. The data support the hypothesis that increased Na+-Ca2+-exchange could favour malignant ventricular arrhythmias.

Biological Transport↗
PubMed2002

Endovascular treatment of thoracic aortic dissection and its variants.

The acute aortic syndrome (AAS) is described. Its pathophysiology is discussed for each of the three entities (penetrating aortic ulcer, intramural hematoma and aortic dissection). The natural history of these three pathologies is reviewed. Diagnostic features and investigation imaging techniques are summarized. The technique of stentgraft-placement is described in detail. The authors report their clinical experience with 127 patients, presenting acute type B aortic dissection or its variants, and treated with an endovascular stent-graft-device. These results are in part compared with a group of control patients with acute type B dissection, submitted to medical non-invasive therapy.

Acute Disease↗
PubMed2002

Ventilating with tracheal gas insufflation and periodic tracheal occlusion during sleep and wakefulness.

INTRODUCTION: The current invasive and noninvasive methods for delivering long-term ventilatory support rely on cumbersome patient interfaces that may interfere with upper airway function. To overcome these limitations, a novel system was developed to ventilate conscious, spontaneously breathing dogs through a self-contained cuffed cannula that was used for tracheal gas insufflation (TGI) and periodic tracheal occlusion (PTO). We hypothesized that TGI + PTO would provide greater ventilatory support than would TGI alone and that its effect would be more pronounced during sleep than wakefulness. METHODS: Chronically tracheostomized dogs were monitored for sleep (ie, EEG, electro- oculogram, and nuchal electromyogram) and breathing (ie, tracheal pressure [Ptr] and upper airway flow via snout mask). A thin transtracheal cannula housed within a cuffed tracheostomy tube was used for TGI and PTO monitoring. E, gas exchange, and breathing patterns were examined during sleep and wakefulness at baseline (ie, no TGI) and during the application of TGI alone (at 5, 10, and 15 L/min) and the application of TGI + PTO. RESULTS: Compared to baseline breathing without TGI, TGI at 5, 10, and 15 L/min decreased minute ventilation without influencing PaCO(2). In contrast, TGI + PTO led to progressive increases in ventilation, positive Ptr swings, and decreases in PaCO(2) as the flow rate was increased during sleep and wakefulness. Moreover, spontaneous breathing efforts ceased during TGI + PTO at flow rates of 10 and 15 L/min during wakefulness, and at all flow rates during sleep. CONCLUSIONS: The findings indicate that TGI + PTO can fully support ventilation in a spontaneously breathing canine model during sleep and wakefulness. Its streamlined interface could ultimately prove to be clinically significant, once technical concerns are addressed.

Animals↗
PubMed2001

Cytotoxic T lymphocyte antigen 4 and CD28 modulate cell surface raft expression in their regulation of T cell function.

Coreceptors CD28 and cytotoxic T lymphocyte antigen (CTLA)-4 have opposing effects on TcR/CD3 activation of T cells. While CD28 enhances and CTLA-4 inhibits activation, the underlying molecular basis of these effects has yet to be established. In this context, ganglioside and cholesterol enriched membrane microdomains (rafts, GEMs) serve as centers of signaling in T cells. Although CD28 can promote TcR/raft colocalization, evidence is lacking on whether the surface expression of membrane rafts can be targeted by CTLA-4 in its modulation of T cell responses. In this study, we demonstrate that both CD28 and CTLA-4 profoundly alter the surface expression of membrane rafts during T cell activation. While CD28 increased expression and the number of peripheral T cells induced to express surface rafts in response to TcR ligation, CTLA-4 potently inhibited both TcR and TcR x CD28 induced raft expression on the surface of T cells. Consistent with this, CD28 increased the presence of the linker of activated T cells (LAT) in purified membrane rafts, while CTLA-4 coligation effectively blocked this increase. Further, the reversal of the CTLA-4 block with CD3/CD28 ligation was accompanied by an increase in surface raft expression and associated LAT. Our observations demonstrate for the first time that CTLA-4 targets the release of rafts to the surface of T cells, and provides a mechanism for the opposing effects of CD28 and CTLA-4 on costimulation.

Abatacept↗
PubMed2001

Src kinases Fyn and Lck facilitate the accumulation of phosphorylated CTLA-4 and its association with PI-3 kinase in intracellular compartments of T-cells.

Src kinases bind to surface receptors and mediate signaling events at the surface of cells. Little is known regarding whether these kinases can mediate events within intracellular compartments. The T-cell antigen CTLA-4 resides primarily in the trans-Golgi network (TGN), and as such could serve as a model to study the intracellular function of src kinases in their ability to phosphorylate the receptor. In this study, we show that tyrosine kinases p56lck and p59fyn phosphorylate the cytoplasmic domain of CTLA-4 in T-cells. Most interestingly, these kinases are also found in the Golgi apparatus, the intracellular compartment where most of CTLA-4 is localized. Transfection of Lck or Fyn resulted in increased phosphorylation of intracellular CTLA-4 and recruitment of PI-3 kinase. By contrast, phosphorylation did not influence the presence of the receptor in the TGN. These data demonstrate that src kinases operate to modulate receptor binding to intracellular signaling proteins introducing the possibility that intracellular forms of receptors may generate growth signals.

Abatacept↗
PubMed2001

Effects of 5-aminolaevulinic acid on human ovarian cancer cells and human vascular endothelial cells in vitro.

Results are reported on the cellular effects and the sensitivity of cultured tumor epithelial cells (TEC) derived from human ovarian cystadenocarcinoma and human umbilical vein-derived endothelial cells (HUVEC) to exogenous 5-aminolaevulinic acid (ALA) and ALA-induced photodynamic therapy (PDT). Cellular alterations and PDT efficiency were evaluated using colorimetric thiazolyl blue (MTT) assay, trypan blue exclusion assay, electron microscopy, and gel electrophoresis. ALA-induced protoporphyrin IX (PpIX) accumulation in TEC was associated with a concentration and time-dependent significant decrease in mitochondrial activity, increase in cell membrane permeability, and dark toxicity. Maximum PpIX loaded TEC demonstrated a high sensitivity to PDT. Neither cellular alterations nor PDT effects were observed in HUVEC under identical experimental conditions. These results indicate a potential clinical value for the use of ALA-mediated PDT to treat minimal residual disease in mucinous ovarian carcinoma. In addition, the ALA-induced PpIX cytotoxicity may be exported to a new chemotherapeutic regimen via a conventionally viewed photochemotherapeutic agent.

Aminolevulinic Acid↗