Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 19 recordsLinked to original sources

PubMed2006

A meta-analysis of quantitative trait loci associated with body weight and adiposity in mice.

OBJECTIVE: Cross-breeding experiments with different mouse strains have successfully been used by many groups to identify genetic loci that predispose for obesity. In order to provide a statistical assessment of these quantitative trait loci (QTL) as a basis for a systematic investigation of candidate genes, we have performed a meta-analysis of genome-wide linkage scans for body weight and body fat. DATA: From a total of 34 published mouse cross-breeding experiments, we compiled a list of 162 non-redundant QTL for body weight and 117 QTL for fat weight and body fat percentage. Collectively, these studies include data from 42 different parental mouse strains and >14,500 individual mice. METHODS: The results of the studies were analyzed using the truncated product method (TPM). RESULTS: The analysis revealed significant evidence (logarithm of odds (LOD) score >4.3) for linkage of body weight and adiposity to 49 different segments of the mouse genome. The most prominent regions with linkage for body weight and body fat (LOD scores 14.8-21.8) on chromosomes 1, 2, 7, 11, 15, and 17 contain a total of 58 QTL for body weight and body fat. At least 34 candidate genes and genetic loci, which have been implicated in regulation of body weight and body composition in rodents and/or humans, are found in these regions, including CCAAT/enhancer-binding protein alpha (C/EBPA), sterol regulatory element-binding transcription factor 1 (SREBP-1), peroxisome proliferator activator receptor delta (PPARD), and hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1). Our results demonstrate the presence of numerous distinct consensus QTL regions with highly significant LOD scores that control body weight and body composition. An interactive physical map of the QTL is available online at (http://www.obesitygenes.org).

Adipose Tissue↗

PubMed2006

Impact of trisomy on fertility and meiosis in male mice.

BACKGROUND: Chromosomal abnormalities frequently are associated with impairment or arrest of spermatogenesis in mammals but are compatible with fertility in female carriers of the same anomaly. In the case of trisomy, mice have extra genomic DNA as well as the chromosomal abnormality, usually present as an extra, unpaired chromosome. Thus, impairment of spermatogenesis in trisomic males could be due to the presence of extra genomic material (i.e. triplicated genes) or due to the chromosomal abnormality and presence of an unpaired chromosome in meiosis. METHODS: In this study, fertility and chromosomal pairing configurations during meiotic prophase were analysed in male mice trisomic for different segments of the genome. Four have an extra segmental or tertiary trisomic chromosome--Ts(17(16))65Dn, Ts(10(16))232Dn, Ts(12(17))4Rk and Ts(4(17))2Lws--and one has the triplicated segment attached to another chromosome--Ts(16C-tel)1Cje. Ts(17(16))65Dn and Ts(16C-tel)1Cje have similar gene content triplication and differ primarily in whether the extra DNA is in an extra chromosome or not. RESULTS: The presence of an intact extra chromosome, rather than trisomy per se, is associated with male sterility. Additionally, sterility is correlated with a high frequency of association of the unpaired chromosome with the XY body, which contains the largely unpaired X and Y chromosomes. CONCLUSIONS: Intact extra chromosomes disrupt spermatogenesis, and unpaired chromosomes establish a unique chromatin territory within meiotic nuclei.

Animals↗

PubMed2006

Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's disease.

BACKGROUND: In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. AIM: To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. METHODS: Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. RESULTS: Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1-45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. CONCLUSIONS: In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy.

Adult↗

PubMed2006

Assessment of the environmental impact of landfill sites with open combustion located in arid regions by combined chemical and ecotoxicological studies.

Two different waste disposal sites in Jordan were investigated in order to determine the environmental situation in context with waste disposal techniques. One landfill, located at Marka/Amman, had been closed about 25 years ago and covered with soil. Here, the waste had been actively open combusted and openings in the cover, still emitting smoke, indicated that waste was still smoldering inside the landfill's body. The second disposal site close to Ekeeder/Irbid is still operated. On this ground, the solid waste is not intentionally burned, although spontaneous fires frequently come up. Samples of waste, soil, and entrained dust were collected and analyzed. From the solid samples, respectively, their eluates, sum parameters, ecotoxicological effects as well as contents of elements/heavy metals and organic pollutants (PAH, PCDD/F) were determined. In general, the Ekeeder-samples were low-contaminated. The investigation of the Marka-samples showed higher contamination of the site's center, clearly being influenced by combustion processes. A significant contamination of the landfill's vicinity by its emissions could not be derived from the analytical data. Ecotoxicological investigations, applying a bio-test battery, revealed correlations with the sum parameters but not with the trace pollutants. Thus, the Marka-samples with the highest measured values of sum parameters caused adverse effects on three different test species, whereas other samples from Marka and Ekeeder had small or no effects. The results of these investigations depict the influence of different disposal techniques on the contamination situation of a landfill and they shall contribute to assess the conditions of other disposal sites in (semi)arid regions.

Benzofurans↗

PubMed2006

Endothelial and epithelial expression of eotaxin-2 (CCL24) in nasal polyps.

BACKGROUND: Nasal polyposis is mostly associated with eosinophilia of mucosal tissue. This points to the implication of CC chemokines in nasal eosinophilia. Recently the CC chemokine eotaxin-2 (CCL24) was identified. This study was initiated to localize the cellular source, analyze expression of mRNA, and quantify protein synthesis of CCL24. METHODS: Specimens of nasal inferior turbinates from controls and polypous tissue from patients suffering from chronic polypous sinusitis were collected. Furthermore, fibroblasts and epithelial cells were cultured. CCL24 protein was analyzed by immunohistochemistry and ELISA, expression of mRNA by SQ-RT-PCR. RESULTS: CCL24 was observed in endothelial and epithelial cells. Specimens from patients expressed significantly (>2fold) more CCL24 mRNA than controls. Fibroblasts and unstimulated cells did not express CCL24 mRNA. Upon stimulation with TNF-alpha, INF-gamma, IL-4, or costimulation with TNF-alpha and INF-gamma CCL24 mRNA was significantly enhanced (3.2-19.6%). In controls, fibroblast, and unstimulated cells CCL24 protein was below detection limit. Most polyps comprised significant amounts of CCL24 (mean 0.24 ng/mg). TNF-alpha, INF-gamma or IL-4 induced CCL24 protein (0.1-0.3 ng/ml) in epithelial cells. Costimulation with TNF-alpha and IL-4 (0.1-30 and 1-30 ng/ml, respectively) synergistically induced synthesis of CCL24 protein (0.18-0.31 ng/ml). CONCLUSION: In nasal polyps endothelial and epithelial cells are obviously the main source of CCL24, which was shown for transcription (mRNA) and production (protein) levels and was associated with diseases. Results gave evidence of CLL24- directed migration of cells from inside (the bloodstream) to the epithelial side (mucosa) in eosinophilic inflammatory diseases, e.g. nasal polyposis.

Adolescent↗

PubMed2006

Retroperitoneal gas gangrene after colonoscopic polypectomy without bowel perforation in an otherwise healthy individual: report of a case.

BACKGROUND: Abdominal gas gangrene caused by clostridia species is rare and usually associated with organ perforation, immune suppression, or advanced malignoma. CASE REPORT: A 61-year-old man was admitted with severe back pain 1 day after uncomplicated colonoscopic polypectomy. With the exception of preexisting minor depression, the patient had been previously in excellent health. The computed tomography scan showed retroperitoneal emphysema in the left psoas muscle. During exploratory laparotomy, a spreading retroperitoneal phlegmon with pneumoretroperitoneum and a secondary peritonitis were found. A macroscopic perforation of the gut, particularly at the polypectomy sites was excluded. After the operation, the patient evolved in a septic shock condition and had pulmonary failure. Before hyperbaric oxygen therapy could be employed, the patient died. The autopsy showed a massive gas gangrene of the retroperitoneum caused by Clostridium perfringens, but no macroscopic bowel perforation was detected. RESULTS: This is the first report of a case of gas gangrene after uncomplicated polypectomy without macroscopic perforation in an otherwise healthy individual. A microperforation due to mucosal defect after polypectomy was most likely the entry point for the bacteria. CONCLUSION: We conclude that clostridial myonecrosis should be considered in unclear abdominal infections, even if the patient's history is not typical as in the present case.

Clostridium perfringens↗

PubMed2006

[Multimodal treatment of colon cancer?].

Surgical therapy is still the basis of therapy of patients with colon carcinoma. Multimodal therapeutical concepts are presently applied as a therapeutical standard in the adjuvant therapy and increasingly in the systemic therapy of patients with primarily inoperable metastases of the liver to reach a secondary operability. Interdisciplinary multimodal therapeutical concepts are even accepted within the therapy of metastasized colon carcinomas. There are still unanswered questions regarding sequences of palliative systemic therapies and their combinations with local ablative methods.

Antineoplastic Agents↗

PubMed2006

[Vocational rehabilitation in transition--challenges and perspectives].

The present article outlines the challenges in occupational rehabilitation arising from the successive erosion of the financial foundations of the welfare system, from changes in industry as well as in health, education and labour-market policy. Five perspectives are discussed to design and develop strategies in occupational rehabilitation. Among these are: (1) Rehabilitation in companies is mostly based on miscarried efforts to prevent separation. The discontinuance and the re-integration in a position or in a company have therefore to be regarded as an interlocking process between vocational training centre, social insurance agencies and employers; (2) Regional vocational rehabilitation centres with the objective to promote participation in work life may advance to institutionalized junctions to connect the rehabilitation landscape and would represent the logistic context; (3) The development of participation benefits should mainly be directed towards individualized allocation of resources as well as the possibility of direct transfer to work in close cooperation with employers; (4) Structural solutions and process-innovation could be supported by application-orientated research; (5) A new consensus to assign future tasks and objectives should be defined among the responsible bodies and service organisations involved in occupational rehabilitation.

Persons with Disabilities↗

PubMed2006

Levosimendan: a promising treatment for myocardial stunning?

We report a case of a 55-year-old male undergoing major orofacial cancer surgery. A stent to the left anterior descending artery had been implanted for ischaemic heart disease 3 years previously. Twenty-four hours after uneventful anaesthesia and surgery, the patient developed myocardial infarction and cardiogenic shock. Immediate percutaneous transluminal coronary angioplasty, intra aortic balloon counterpulsation, and catecholamine therapy failed to stabilise haemodynamics. In light of successful reperfusion therapy and an only moderate elevation of troponin I, myocardial stunning rather than myonecrosis was considered to be the major contributor to life-threatening left ventricular failure. Therefore, the calcium-sensitising drug levosimendan, which exerts positive inotropic activity without increasing myocardial oxygen demand, was administered as a rescue medication. Within 24 h, levosimendan resulted in decreased filling pressures, reduced left ventricular end-diastolic volume, and augmented systemic pressures. Seven days following surgery, the patient was discharged from the intensive care unit in good clinical condition.

Cardiotonic Agents↗

PubMed2006

Functional characterization of SLC7A9 polymorphisms assumed to influence the cystinuria phenotype.

Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3-A1 gene cause type I cystinuria, patients with non-type I cystinuria mostly carry mutations in the SLC7A9 gene. However, there is evidence that further genetic factors cause and influence the cystinuria phenotype. We recently demonstrated that specific polymorphisms in Exons 3, 4, 5 and 6 of the SLC7A9 gene show a significant different allelic distribution between cystinuria patients and controls. To determine the role of the variants in these exons we transfected COS7 cells with expression constructs containing different haplotypes. Sequencing of cDNAs derived from the resulting SLC7A9 mRNAs did not reveal any differences in expression between the minigenes of the specific haplotypes. Our findings suggest that the variants in SLC7A9 do not influence splicing behavior. Thus, the reasons for the different allelic distribution between cystinuria patients and controls remain unclear. It is conceivable that this distribution is caused by the association of certain alleles with so far undetected mutations in the gene.

Amino Acid Transport Systems, Basic↗

PubMed2005

apoB/apoA-I ratio is related to femoral artery plaques and is predictive for future cardiovascular events in healthy men.

OBJECTIVES: The aim of the present study was to investigate the association between serum concentrations of apoB, apoA-I and the apoB/apoA-I ratio and future cardiovascular events in a group of healthy 58-year-old men during 6.6 years of follow-up. A further aim was to investigate the concentrations of apoB, apoA-I and the apoB/apoA-I ratio to the association of plaque occurrence in the carotid and femoral arteries. BACKGROUND: Previous studies have shown that the apoB/apoA-I ratio is an important cardiovascular risk factor, whereas the association between apoB/apoA-I ratio and presence of atherosclerotic plaques in the carotid and femoral arteries has been less investigated. METHODS: The carotid and femoral arteries were examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Göteborg, Sweden. Assessment of plaque occurrence and measurement of apolipoproteins (apoA-I and apoB) was performed. RESULTS: Subjects with an apoB/apoA-I ratio >/=0.9 had a significantly increased risk to suffer a cardiovascular event during 6.6 years of follow-up (OR 3.07, 95% CI 1.22-7.71), while no difference in risk for cardiovascular events was observed for subjects with LDL cholesterol >3.4 mmol/L compared to subjects <3.4 mmol/L (OR 1.04, 95% CI 0.37-2.46). A greater risk for plaques in the femoral artery was also observed in subjects with an apoB/apoA-I ratio >/=0.9 compared to subjects <0.9 (OR 3.06, 95% CI 1.22-7.70). In a multiple logistic regression model, both elevated apoB/apoA-I ratio and plaque occurrence in the femoral artery were of significant importance for cardiovascular events during follow-up. CONCLUSIONS: The results showed that the apoB/apoA-I ratio was associated with arteriosclerosis in the femoral artery, and predicted future cardiovascular events. These observations, and the fact that apoB and apoA-I can be measured in the non-fasting state with high precision, in combination with the finding that LDL cholesterol did not predict cardiovascular disease, support results from other studies that the apoB/apoA-I ratio may be a superior risk marker for cardiovascular disease.

Apolipoprotein A-I↗

PubMed2005

Comparison of electrical velocimetry and transoesophageal Doppler echocardiography for measuring stroke volume and cardiac output.

BACKGROUND: Impedance cardiography (ICG) has been used extensively to estimate stroke volume (SV) and cardiac output (CO) from changes of thoracic electrical bioimpedance (TEB). However, studies comparing ICG with reference methods have questioned the reliability of this approach. Electrical velocimetry (EV) provides a new algorithm to calculate CO from variations in TEB. As the transoesophageal Doppler echocardiographic quantification of CO (TOE-CO) has emerged as a reliable method, the purpose of this study was to determine the limits of agreement between CO estimations using EV (EV-CO) and TOE-CO. METHODS: Standard ECG electrodes were used for non-invasive EV-CO measurements. These were placed on 37 patients scheduled for coronary artery surgery necessitating transoesophageal echocardiography monitoring. Simultaneous EV-CO and TOE-CO measurements were recorded after induction of anaesthesia. EV-CO was calculated using the Bernstein-Osypka equation. TOE-CO was measured across the aortic valve using continuous-wave Doppler echocardiography and a triangular orifice model. RESULTS: A significant high correlation was found between the TOE-CO and the EV-CO measurements (r2=0.86). Data were related linearly. The slope of the line (1.10 (se 0.07)) was not significantly different from unity, and the point at which it intersected the ordinate (-0.46 (0.32) litre min(-1)) was not significantly different from zero. Bland-Altman analysis revealed a bias of 0.18 litre min(-1) with narrow limits of agreement (-0.99 to 1.36 litre min(-1)). CONCLUSIONS: The agreement between EV-CO and TOE-CO is clinically acceptable, and these two techniques can be used interchangeably.

Adult↗

PubMed2005

Chlamydophila pneumoniae and Mycoplasma pneumoniae in respiratory specimens of children with chronic lung diseases.

BACKGROUND: Persistent infection with Mycoplasma pneumoniae and Chlamydophila pneumoniae has been implicated in the progression or induction of asthma and chronic obstructive pulmonary disease. Evidence for this hypothesis has been obtained in adults either by serological methods or by direct pathogen detection using invasive procedures. METHODS: We investigated nasal brush specimens and induced sputum from 38 children with stable chronic lung disease (asthma, n = 26; chronic bronchitis n = 12) and from 42 healthy controls for the presence of M pneumoniae or C. pneumoniae DNA by polymerase chain reaction (PCR) using nested primers. RESULTS: None of the controls but 23.6% and 10.5% of the children with lung disease had positive PCR for C pneumoniae (p = 0.001) and M pneumoniae (p = 0.044) respectively. Significantly more children with non-atopic asthma than with atopic asthma were positive for C pneumoniae or M pneumoniae (4/8 v 1/18; p = 0.018). There were no unwanted side effects from sputum induction. No correlation was found between detection of Chlamydophila and severity of lung disease. Colonisation with both organisms had occurred before adulthood in a significant proportion of children with stable chronic lung diseases. CONCLUSION: Combining nasal brush specimens with induced sputum may be a useful non-invasive method for studying the role of C pneumoniae and M pneumoniae infection in children with different chronic lung diseases.

Adolescent↗

PubMed2005

Increased cytokine transcripts in pouchitis reflect the degree of inflammation but not the underlying entity.

BACKGROUND AND AIMS: After ileopouch anal anastomosis (IPAA), 10-40% of patients with ulcerative colitis (UC) but only 5% of patients with familial adenomatous polyposis (FAP) develop pouchitis. Immunoregulatory abnormalities might be of importance in the pathogenesis of the disease. Therefore, we characterized cytokine and chemokine transcripts in inflamed and non-inflamed pouches in patients with UC compared to those with FAP and Crohn's disease (CD). PATIENTS AND METHODS: Mucosal biopsies were taken from 87 patients with IPAA [UC (n=70), CD (n=8) or FAP (n=9)]. Patients with active ileal CD (n=14), active UC (n=17) and non-inflammatory conditions (n=12) served as controls. The expression of 20 gene transcripts was quantified using real-time polymerase chain reaction. RESULTS AND FINDINGS: Pro-inflammatory cytokines and chemokines are significantly increased in IPAA patients with acute pouchitis. This increase is independent of the underlying disease (UC or CD) and reflects the degree of inflammation. A good correlation between pouchitis activity (using the Pouchitis Disease Activity Index) and the MRP-14, interleukin-8, macrophage inflammatory protein-2alpha and matrix metalloproteinase-1 transcripts was observed. INTERPRETATIONS AND CONCLUSIONS: Our data support the view that pouchitis reflects an inflammatory process that is different from that of underlying inflammatory bowel diseases, as the cytokine and chemokine patterns in pouchitis are neither typical of CD nor of UC, but maybe due to bacterial intestinal microflora overgrowth in the pouch lumen. Quantification of transcript levels allows an estimation of the extent of mucosal inflammation and may become helpful in the evaluation of the disease, especially in clinical trials.

Adolescent↗

PubMed2005

An intronic base alteration of the CHRNE gene leading to a congenital myasthenic syndrome.

Reported is a patient with a congenital myasthenic syndrome due to two compound heterozygous mutations of the CHRNE gene. The molecular consequences of a novel intronic base alteration (CHRNE IVS5-16GA) remote from the splice acceptor site were investigated in vivo and in vitro. In conclusion, RNA analysis may be necessary to reveal unexpected splicing aberrations due to intronic mutations that are not part of the consensus splice site.

Adolescent↗

PubMed2005

Oral evaluation in rabbits of cyclosporin-loaded Eudragit RS or RL nanoparticles.

The hydrophobic cyclic undecapeptide cyclosporin A (CyA) used in the prevention of graft rejection and in the treatment of autoimmune diseases was encapsulated by nanoprecipitation within non-biodegradable polymeric nanoparticles. The effect of polymers (Eudragit RS or RL) and additives within the alcoholic phase (fatty acid esters and polyoxyethylated castor oil) on the size, zeta potential and the encapsulation efficiency of the nanoparticles was investigated. The mean diameter of the various CyA nanoparticles ranged from 170 to 310 nm. The size as well as the zeta potential increased by adding fatty acid ester and polyoxyethylated castor oil within the organic phase. No significant differences in surface potential were observed for all formulations tested. Probably due to the very low water solubility of the drug, high encapsulation efficiencies were observed in a range from 70 to 85%. The oral absorption of CyA from these polymeric nanoparticles was studied in rabbits and compared to that of Neoral capsule. Based on comparison of the area under the blood concentration-time curve values, the relative bioavailability of CyA from each nanoparticulate formulation ranged from 20 to 35%.

Acrylic Resins↗

PubMed2005

[Diclofenac inhibits proliferation and matrix formation of osteoblast cells].

Cell culture studies have shown that NSAID may influence osteogenic activities of osteoblast cultures. However, these studies did not consider long-term effects on differentiating cells. The influence of Voltaren with the non-steroidal agent diclofenac on proliferation and gene expression of the osteoblast-like cell line SaOS-2 was investigated 2, 9, and 16 days after incubation. Two days after 24 h of incubation, 50 microg/ml diclofenac reduced the proliferation and collagen type I expression while 9 and 16 days later no effect was found on either of the parameters. In contrast, 50 microg/ml NSAID has no effect on alkaline phosphatase expression 2 days after incubation while 9 and 16 days later expression had been reduced. Lower concentrations (1.56 and 0.19 microg/ml) had no effects on the studied parameters. BrdU and MTT test showed that 50 microg/ml diclofenac reduced proliferative and metabolic activity. Lower concentrations (< or =25 microg/ml) had a lower or no influence. The findings indicate that the NSAID impairment depends on cellular differentiation stage and is not confined to the time during or immediately after NSAID incubation. According to these results in vitro testing of drugs should be performed over a longer time period to detect possible long-term impacts.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry.

To evaluate the significance of inborn metabolic disorders of the pyrimidine degradation pathway, 450 children with unspecific neurological symptoms were comprehensively studied; 200 healthy children were recruited as controls. Uracil and thymine as well as their degradation products in urine were determined with an improved method based on reversed-phase HPLC coupled with electrospray ionization tandem mass spectrometry and detection by multiple-reaction monitoring using stable-isotope-labelled reference compounds as internal standards. From the results of the control group we established age-related reference ranges of all pyrimidine degradation products. In the patient group, two children with dihydropyrimidine dehydrogenase (DPYD) deficiency were identified; one of these was homozygous for the exon 14-skipping mutation of the DPYD gene. In addition, two patients with high uracil, dihydrouracil and beta-ureidopropionate were found to have ornithine transcarbamylase deficiency. In the urine of 9 patients, beta-alanine was markedly elevated owing to treatment with vigabatrin, an irreversible inhibitor of GABA transaminase, which interferes with beta-alanine breakdown. Four patients had exclusively high levels of beta-aminoisobutyrate (beta-AIB) due to a low activity of the D-beta-AIB-pyruvate aminotransferase, probably without clinical significance. In conclusion, quantitative investigation of pyrimidine metabolites in children with unexplained neurological symptoms, particularly epileptic seizures with or without psychomotor retardation, can be recommended as a helpful tool for diagnosis in clinical practice. Sensitive methods and age-related reference ranges enable the detection of partial enzyme deficiencies.

Adolescent↗