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C Schmid

Publications and source records attributed to C Schmid.

At least 55 records · Page 3Linked to original sources
PubMed2002

[Dose-reduced conditioning before allogeneic stem cell transplantation: principles, clinical protocols and preliminary results].

BACKGROUND AND OBJECTIVE: In the treatment of leukemia by stem cell transplantation, the immunological effects of allogeneic T-lymphocytes presumably play a greater part than high-dosage total-body irradiation (TBI) and chemotherapy. Using this immunological effect, attempts are currently being made to reduce the dosage of pre-treatment that is toxic to stem cell, such as TBI, thereby making transplantation available for a larger group of patients at high risk for transplantation. This study presents preliminary results of three current studies of this approach. PATIENTS AND METHODS: Elderly patients with chronic myeloid leukemia (CML) have an increased transplantation risk. They were conditioned with TBI that was reduced stepwise (n = 27). Patients with advanced and refractory myeloid leukemia were treated with chemotherapy and dose-reduced TBI (FLAMSA protocol; n = 54). In patients with multiple myeloma, autologous transplantation with high-dose chemotherapy preceded allogeneic transplantation possible after dose-reduced conditioning (Tandem protocol; n = 6). RESULTS: All three protocols of TBI gave results that were not worse than those of previous studies. Relapse ocurred not more frequently in patients with CML. In patients with high-risk AML the FLAMSA protocol gave better results. Autologous-allogeneic tandem transplantation was well tolerated and led to a good response in all patients. CONCLUSION: Allogeneic transplantation after dose-reduced conditioning opens up new possibilities with respect to widening indications for transplantation and improving results in hematological diseases with previously unsatisfactory treatment.

Adolescent↗
PubMed2002

[Myocardial alterations with mechanical left ventricular assist devices].

Left ventricular assist devices (LVAD) have been used to "bridge" patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called "reverse remodeling", the underlying biological mechanisms are still unclear. Various molecular pathways of the human myocardium associated with apoptosis, response to stress, or matrix changes are known to be altered under conditions of heart failure, and some have been shown to be reversibly regulated during left ventricular mechanical support, suggesting that the descriptive term "reverse remodeling" is, at least in parts, a reversible mechanism. The reduction of volume and pressure overload with a decrease of ventricular wall stress leading to an improvement of myocardial blood supply under mechanical circulatory assistance, may be one explanation for the molecular myocardial changes and may reflect one possible cause for the phenomenon of "reverse remodeling".

Animals↗
PubMed2002

[Malignomas following heart transplantation].

Up to 30% of patients with an organ transplantation develop precancerous lesions and malignant tumors, especially of the skin. All 241 patients who underwent heart transplantation from 1990 to 2000 were evaluated with regard to the development of neoplasias. Those alive in September 1999 were referred for a standardized dermatological exam (n=156) which detected malignancy in 28 patients being transplanted for 4.98 years on average. The skin was the organ most frequently involved (64%, n=18). 18% (n=5) of tumors were found in the urinary and genital tract, 7% (n=2) each in the respiratory and gastrointestinal tract, and 4% (n=1 ) in the breasts. The average age of patients who developed tumors was significantly higher as compared to the overall mean age (59.5+/-5 vs 49.8+/-14.7 years, p=0.00027). There was no correlation between development of malignancy and HLA matching, immunosuppressive drugs used, dosage and serum levels of immunosuppressive medication, and episodes of transplant rejection. Our study shows that the risk to develop tumors is at least doubled after heart transplantation. Due to the high incidence of skin tumors, transplant patients should undergo dermatological examinations on a regular basis.

Age Factors↗
PubMed2002

Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts.

NF-kappaB/Rel transcription factors are modulators of immune and inflammatory processes and are also involved in malignancy. Phosphorylation of the IkappaB inhibitors by the IkappaB kinase (IKK) complex leads to their proteasomal degradation, resulting in activated NF-kappaB. Here, we investigated the activation status of NF-kappaB and the IKK complex in acute myeloid leukemia (AML). Gelshift assays revealed an increased level of activated nuclear NF-kappaB in myeloid blasts. Both bone marrow and peripheral blood blasts from AML patients showed enhanced IKK activity relative to controls, whereas the IKK protein concentrations were comparable. In addition, an increased level of IkappaB-alpha was detected in AML blast cells, although this appeared to be insufficient to block nuclear translocation of NF-kappaB, also confirmed by immunofluorescence. In subtype M4 and M5 AML cells a more extensive NF-kappaB activation and higher IKK activity was found than in M1/M2 specimens. Isolated AML blasts cultured ex vivo responded to external stimulation (TNF, LPS) by further IKK activation, IkappaB degradation and NF-kappaB activation. Preincubation with the proteasome inhibitor PSI inhibited the NF-kappaB system in isolated AML blasts. This study established for the first time a dysregulation of IKK signaling in AML leading to increased NF-kappaB activity suggesting potential therapeutic avenues.

Acute Disease↗
PubMed2002

A plasma glucose concentration below 2.5 mmol L-1 is not an appropriate criterion to end the 72-h fast.

CONTEXT: The classical end-point to terminate the 72-h fast in a patient evaluated for a hypoglycaemic disorder is the occurrence of hypoglycaemic symptoms in association with a low plasma glucose level. However, neither the symptoms nor the plasma glucose level have been exactly defined. OBJECTIVE: To determine whether a useful cut-off plasma glucose concentration as criterion to end the prolonged fast in the absence of neuroglycopenic symptoms can be defined. DESIGN: Single centre case-control study. SETTING: Tertiary referral hospital in Switzerland. SUBJECTS: The 72-h fast was prospectively performed in 23 consecutive patients (17 women and six men) following a standardized protocol between July 1999 and January 2002. All patients were referred to our clinic for evaluation of suspected hypoglycaemia. The criterion to end the fast before 72 h was defined by the occurrence of symptoms or signs typical for neuroglycopenia irrespective of plasma glucose levels. MAIN OUTCOME MEASURE: Insulin levels and insulin to plasma glucose ratios in insulinoma patients and in individuals without insulin-secreting tumours at termination of the fast and at plasma glucose levels </=2.5 mmol L-1, prior to the occurrence of neuroglycopenic symptoms. RESULTS: In seven patients, the fast was terminated before 72 h because they developed neuroglyco-penic symptoms. Insulin-secreting tumours were found and successfully removed in these seven patients. Sixteen individuals developed no neuroglycopenic symptoms throughout the 72-h fast and an insulin-secreting tumour could be excluded in these 16 patients. Five of these 16 individuals had plasma glucose levels </=2.5 mmol L-1 during the 72-h fast. Insulin levels and insulin to glucose ratios in insulinoma patients and healthy individuals overlapped during as well as at termination of the fast. Prior to the occurrence of neuroglycopenic symptoms and at venous plasma glucose </=2.5 mmol L-1, insulin to plasma glucose ratios dropped in insulinoma patients to values within the normal range on several occasions. CONCLUSIONS: Terminating the fast at plasma glucose levels </=2.5 mmol L-1 does not allow confirmation or exclusion of an insulin-secreting tumour. Thus, the occurrence of symptoms or signs typical for neuroglycopenia is the prerequisite criterion to end the fast before 72 h.

Adolescent↗
PubMed2002

When should we consider right ventricular support?

Ventricular assist systems have become an important tool in the surgical management of acute and chronic heart failure. While indications for left ventricular support ar e well established, criteria for right ventricular support are much less defined. This report summarizes current knowledge on the implantation of right ventricular support in clinical settings of isolated right heart failure, biventricular failure, postcardiotomy failure and post-LVAD right heart failure.

Cardiac Output, Low↗
PubMed2002

Jehovah's Witnesses--how to encounter the transfusion issue.

Surgical management is different for Jehovah's Witnesses than in customary operations. Preoperative measures primarily aim at an optimal hematological condition, whereas intraoperative activities are directed towards minimizing blood loss. However, physicians taking care of Jehovah's Witnesses are not only faced with the difficulties of adequate treatment, but also by psychological and legal issues. Since the German legal system does not offer clear-cut legislation with regard to the Jehovah's Witnesses transfusion issue, guidelines have been offered on how to encounter his issue.

Blood Transfusion↗
PubMed2002

Left ventricular assist stand-by for high-risk cardiac surgery.

BACKGROUND: Patients with severely impaired left-ventricular pump function who are eligible for heart transplantation increasingly undergo high-risk cardiac surgery due to the scarcity of donor organs. If these patients also qualify for long-term mechanical support, the latter can be used as back-up in case of postcardiotomy failure. METHODS: Since 1994, 36 patients (34 male, 2 female; mean age 51 +/- 7 years) underwent coronary bypass surgery/aneurysmectomy (n = 27), aortic valve replacement (n = 4), both (n = 1), or partial left ventriculectomy (n = 4) with a long-term mechanical assist device (Novacor, HeartMate, DeBakey) and were kept on stand-by with the device. Average left ventricular ejection fraction was 23 +/- 9 %, NYHA 2.9 +/- 0.5, and CCS 2.7 +/- 0.9. An intraaortic balloon pump was inserted prior to surgery in 13 patients. RESULTS: In 31 patients, high-risk surgery was performed, whereas 5 patients underwent immediate device placement as coronary revascularization was deemed impossible. 6 patients had postcardiotomy failure after coronary bypass surgery and were immediately provided with a long-term assist system. There were no significant differences in risk factors between the patient subsets. All conservatively operated patients survived and left the institution after 9.4 days and are currently at NYHA 1.5 +/- 0.5 or CCS 1.0 +/- 0, respectively. 6 of the 11 LVAD patients could be bridged to heart transplantation after 43 - 418 days, and 1 patient is still on support. CONCLUSION: High-risk conventional surgery with LVAD stand-by is feasible and seems to be a valuable alternative for heart-transplant candidates.

Female↗
PubMed2002

Mitral valve surgery in patients with poor left ventricular function.

BACKGROUND: Mitral valve surgery for the correction of secondary mitral valve regurgitation (MR) in cardiomyopathy is associated with a poor outcome. Numerous studies have identified a severe left ventricular dysfunction as an indicator for a poor prognosis. The aim of the study was to asses the follow-up after mitral valve surgery and severe left ventricular dysfunction. METHODS: Between 1994 and 2000, 31 patients with mitral regurgitation and a left ventricular ejection fraction of below thirty percent undergoing isolated repair (n = 16) or replacement (n = 15) were investigated. All patients received maximal drug therapy. Twenty-one patients were New York Heart Association (NYHA) class III and 10 were class IV. Follow-up with echocardiography, ECG, and chest x-ray was performed in 87 % of the survivors. The mean duration of follow-up was 39 +/- 16 months. RESULTS: The mean duration of ICU and hospital stay was 3.6 +/- 2.1 days and 8.1 +/- 5.4 days, respectively. The 1-, 2-, and 5-year survival rates were 91 %, 84 %, and 77 %, respectively. NYHA class improved from 3.3 +/- 0.8 to 2.1 +/- 0.7 at follow-up (p < 0.01). The ejection fraction improved from 23.1 +/- 6.6 % to 36 +/- 6.8 % at follow-up (p < 0.02). Freedom from readmission for heart failure was 85 %, 79 %, and 68 % at 1-, 2-, and 5 years, respectively. CONCLUSIONS: Mitral valve surgery improves left ventricular function and reduces heart failure severity in patients with MR and cardiomyopathy. High-risk mitral valve surgery may be an alternative to heart transplantation in selected patients.

Atrial Fibrillation↗
PubMed2001

Insulin-like growth factor (IGF) I down-regulates type 1 IGF receptor (IGF 1R) and reduces the IGF I response in A549 non-small-cell lung cancer and Saos-2/B-10 osteoblastic osteosarcoma cells.

The insulin-like growth factor type 1 receptor (IGF 1R) mediates the acute metabolic effects of IGF I as well as IGF I-stimulated cell proliferation and protection from apoptosis. IGF binding proteins (IGFBPs) can modulate these responses. We, therefore, investigated whether intrinsic IGFBPs interfere with IGF I-induced regulation of IGF 1R expression and with the biological response to IGF I in two human tumor cell lines, the non-small-cell lung cancer cell line A549 and the osteoblastic osteosarcoma cell line Saos-2/B-10. We compared the growth rates, IGFBP production, IGF I binding characteristics, IGF 1R protein and mRNA levels, and the acute IGF I response (stimulation of glycogen synthesis) after pretreatment of the cells in serum-free medium with or without added IGF I or medium supplemented with 5% fetal calf serum (FCS). In contrast to A549 cells, which produce IGF I and significant amounts of IGFBPs, survival and proliferation of Saos-2/B-10 cells, which do not produce IGF I or significant amounts of IGFBPs, depended on the addition of exogenous IGF I. IGF I increased the concentration of IGFBP-2 and -3 and decreased the concentration of IGFBP-4 in the medium of A549 cells. As compared to FCS, IGF I pretreatment in both cell lines decreased the number of specific IGF I binding sites, down-regulated total and membrane IGF 1R protein, and largely reduced or abolished the acute IGF I response without affecting IGF 1R mRNA levels. The data suggest that the IGF 1R protein of the two cell lines is translationally and/or posttranslationally down-regulated by its ligand in the presence and in the absence of locally produced IGFBPs and that the cell lines have retained this negative feedback to counteract IGF I stimulation.

Apoptosis↗
PubMed2001

Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products.

Proteasomes are the main proteases responsible for cytosolic protein degradation and the production of major histocompatibility complex class I ligands. Incorporation of the interferon gamma--inducible subunits low molecular weight protein (LMP)-2, LMP-7, and multicatalytic endopeptidase complex--like (MECL)-1 leads to the formation of immunoproteasomes which have been associated with more efficient class I antigen processing. Although differences in cleavage specificities of constitutive and immunoproteasomes have been observed frequently, cleavage motifs have not been described previously. We now report that cells expressing immunoproteasomes display a different peptide repertoire changing the overall cytotoxic T cell--specificity as indicated by the observation that LMP-7(-/-) mice react against cells of LMP-7 wild-type mice. Moreover, using the 436 amino acid protein enolase-1 as an unmodified model substrate in combination with a quantitative approach, we analyzed a large collection of peptides generated by either set of proteasomes. Inspection of the amino acids flanking proteasomal cleavage sites allowed the description of two different cleavage motifs. These motifs finally explain recent findings describing differential processing of epitopes by constitutive and immunoproteasomes and are important to the understanding of peripheral T cell tolerization/activation as well as for effective vaccine development.

Amino Acid Sequence↗
PubMed2001

10 Swiss kindreds with multiple endocrine neoplasia type 1: assessment of screening methods.

PRINCIPLES: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterised by the combined occurrence of tumours of the parathyroid glands, the enteropancreatic neuroendocrine system and the anterior pituitary gland. The genetic defect has been mapped to the long arm of chromosome 11q13, and the MEN1-gene was recently identified by positional cloning. Genetic screening for MEN1 germline mutations allows the identification of gene carriers in affected kindreds. Biochemical and radiological screening for MEN1 tumours allows an earlier diagnosis and treatment, and, thus may reduce morbidity and mortality. Since there is no consensus about the frequency and the extent of the necessary screening investigations, evaluation of proposed screening programs is of importance. METHODS: The aims of our study were to identify the MEN1-gene mutations and to detect the gene-carriers in 10 Swiss MEN1 families, as well as to assess biochemical and radiological screening methods. The study included 45 members from 10 MEN1 families. RESULTS: Every family had a different type of MEN1-gene mutation. Thirty out of 45 family members were gene mutation carriers. Twenty-two MEN1-gene carriers had typical MEN1 tumours: parathyroid, enteropancreatic and pituitary tumours were found in 21, 14 and 1 patients, respectively. Applying a defined screening program the following manifestations in asymptomatic MEN1-gene carriers were detected: 9 primary hyperparathyroidism, 3 nonfunctioning pancreatic tumours, 1 gastrinoma, 1 nonfunctioning microadenoma of the pituitary and 1 macronodular adrenal hyperplasia. CONCLUSIONS: The genetic screening facilitates the identification of individuals who carry MEN1-gene mutations, and allows one to exclude non-mutant gene carriers from further investigations. The prospective biochemical and radiological screening of gene mutation carriers allows the earlier detection of MEN1-associated tumours. Therefore, it might be expected that morbidity and mortality of the MEN1 could be reduced.

Adolescent↗