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Biomedical subjects

C Schmid

Publications and source records attributed to C Schmid.

At least 91 records · Page 5Linked to original sources
PubMed2001

Effects of IGF-I and -II, IGF binding protein-3 (IGFBP-3), and transforming growth factor-beta (TGF-beta) on growth and apoptosis of human osteosarcoma Saos-2/B-10 cells: lack of IGF-independent IGFBP-3 effects.

OBJECTIVE: Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits cell growth. Previous reports have suggested the existence of plasma membrane IGFBP-3 receptors that could mediate direct, IGF-independent effects. Thus far, however, the only well-defined putative IGFBP-3 receptor is the type V transforming growth factor-beta (TGF-beta) receptor, a membrane glycoprotein that mediates TGF-beta-induced growth inhibition in selected cells. The aim of the study was to test whether IGFBP-3 and TGF-beta exert short-term effects in an osteosarcoma cell line that produces no IGF but contains type 1 IGF receptors. DESIGN: DNA synthesis and apoptosis in Saos-2/B-10 cells were measured in response to IGF-I, IGF-II, IGFBP-3 and TGF-beta2, and to type 1 IGF receptor ligands with poor affinity for IGFBP-3 ([QAYL]-IGF-I and insulin). RESULTS: IGF-I and IGF-II stimulated thymidine incorporation into DNA and suppressed apoptosis in a dose-dependent manner with maximal effects at 1 and 3 nM respectively. TGF-beta2 slightly increased thymidine incorporation into DNA but had no effect on apoptosis. IGFBP-3 had no effect by itself. Whereas it blocked the above effects of 1 nmol/l IGF-I, it did not block those of 1 nmol/l [QAYL]-IGF-I or 100 nmol/l insulin. CONCLUSIONS: IGFBP-3 does not affect DNA synthesis or apoptosis in an IGF-independent manner in IGF-responsive osteosarcoma cells. It therefore appears to act essentially by sequestration of IGF.

Apoptosis↗
PubMed2001

Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNA(LEU(UUR)) gene mutation.

OBJECTIVE: The effects of glucose, arginine, and glucagon on beta-cell function as well as alpha-cell response to arginine were studied in a family with mitochondrial diabetes. RESEARCH DESIGN AND METHODS: The function of alpha- and beta-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test. RESULTS: The glucose disappearance constant (K(g)) value (mean +/- SEM 0.61 +/- 0.04 vs. 1.1 +/- 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0-10 min, 77.7 +/- 50.7 vs. 1,352.3 +/- 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 +/- 111.4 vs. 1,526.7 +/- 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 +/- 710.8 vs. 1,083.2 +/- 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 +/- 47.5 vs. 90.0 +/- 21.1 pmol/l, P = 0.099). CONCLUSIONS: This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.

Adult↗
PubMed2001

Selection of long-term ventricular assist devices in heart failure patients.

Selection of long-term ventricular assist devices in heart failure patients depends on indication, intention of mechanical support, and availability of devices. Even if many more issues of mechanical support like infection, thromboembolism, and device failure are still unresolved, acceptable results can already be achieved with the current systems.

Equipment Failure↗
PubMed2000

Phex cDNA cloning from rat bone and studies on phex mRNA expression: tissue-specificity, age-dependency, and regulation by insulin-like growth factor (IGF) I in vivo.

Phosphate regulating gene with homology to endopeptidases on the X chromosome (Phex) inactivating mutations cause X-linked hypophosphatemia (XLH). The disorder is characterized by decreased renal phosphate (Pi) reabsorption in both humans and mice, in the latter shown to be due to a reduction in mRNA and protein of type II sodium-dependent phosphate cotransporter (NadPi-II). To gain insight into the physiological role of Phex, we cloned the rat cDNA and examined tissue-specific and age-dependent mRNA expression. The rat full-length cDNA (2247 nucleotides) shares 96 and 90% identity with the mouse and human cDNA, respectively. We found 6.6 kb Phex transcripts in calvarial bone and lungs, and a weaker signal in liver of newborn rats. In adult animals, Phex mRNA signals were weaker in bone and lungs and absent in liver. Phex mRNA expression in bones and NadPi-I and -II cotransporter mRNA expression in kidney were also determined in hypophysectomized rats. These rats, which lack GH and IGF I, stop growing and exhibit decreased serum Pi levels. Treatment during 6 days with IGF I stimulated growth and increased serum Pi. Phex and NadPi-II cotransporter mRNA levels were higher in IGF I than in vehicle-treated animals, while mRNA expression of NadPi-I, 1alpha-hydroxylase and 24-hydroxylase and serum levels of calcitriol remained unaffected. Age-dependency of Phex expression suggests a role for Phex in Pi retention during growth. Moreover, our findings indicate that an increase in Phex expression in bones under the influence of IGF I may contribute to increased serum Pi by enhancing renal phosphate reabsorption. Because IGF I treatment increased NadPi-II mRNA expression and serum Pi, IGF I appears to act at least partially at pretranslational levels to increase NadPi-II mediated renal Pi retention in growing rats.

Aging↗
PubMed2000

[Hypothyroidism and endocrine orbitopathy].

The 34-year old woman, by profession a farmer, presented herself with the symptoms of hypothyroidism, which were confirmed by laboratory investigations. Chronic autoimmune thyroiditis was assumed due to the constellation of primary hypothyroidism in association with elevated thyroid autoantibodies. Substitution with levothyroxine induced a full clinical recovery, but persistent hyperthyroidism occurred even after discontinuation of levothyroxine treatment. Mild ophthalmopathy developed and Graves disease was diagnosed. The primary manifestation of Graves' disease with hypothyroidism was caused by blocking TSH receptor antibodies. Chronic autoimmune thyroiditis, Graves' disease and the importance of thyroid autoantibodies are discussed.

Adult↗
PubMed2000

Osteonecrosis after lung transplantation: cystic fibrosis as a potential risk factor.

BACKGROUND: Osteonecrosis is a known complication after transplantation of solid organs. The incidence of osteonecrosis after lung transplantation is not well documented. METHODS: We investigated the incidence of symptomatic osteonecrosis in lung transplant recipients, transplanted between November 1992 and June 1998 at our institution. For the detection of osteonecrosis, all patients complaining of musculoskeletal pain underwent magnetic resonance imaging. Demographic characteristics, time after transplantation, etiology of underlying lung disease, and the number of steroid pulses for rejection episodes were compared for patients with and without osteonecrosis. RESULTS: Of 63 transplant recipients, all 49 with a follow-up of >3 months were included for analysis. Of seven symptomatic transplant recipients, five cases of osteonecrosis (10%) were detected at a median duration of 216 days (range 44-600) after transplantation. Patients with osteonecrosis have been treated with the same immunosuppressive regimen and with an equal number of steroid pulses for acute rejection episodes (1.4+/-1.1 vs. 1.4+/-1.5, P=0.69), but were younger (26+/-8 vs. 40+/-11 years, P<0.01) than other transplant recipients. Symptomatic osteonecrosis was detected in four of 14 patients (29%) with cystic fibrosis (CF), compared with one osteonecrosis among 35 patients (3%) with other underlying diseases (P<0.02). Within the group of CF patients, specific clinical and demographic characteristics correlating with the risk for subsequent osteonecrosis could not be found. CONCLUSION: In lung transplant recipients, CF may be a risk factor for the development of symptomatic osteonecrosis.

Adolescent↗
PubMed2000

[Spectrum of effectiveness of insulin-like growth factors (IGF)].

The insulin-like growth factors (IGF) I and II mediate endocrine and auto-/paracrine effects of growth hormone (GH) on cell growth, cell differentiation and tissue repair. Despite their insulin-like actions in vitro, they do not play a significant role in the acute regulation of substrate metabolism, as compared to insulin and growth hormone. In contrast, administration of IGF I in vivo causes a broad spectrum of effects: it increases insulin sensitivity, improves the lipid profile, supports protein anabolism, enhances kidney function and bone turnover, and exerts beneficial effects on the cardiovascular system. Understanding of the mechanisms underlying these effects provides the basis for potential therapeutic use of IGF I.

Cell Differentiation↗
PubMed2000

Regional expression of protein phosphatase type 1 and 2A catalytic subunit isoforms in the human heart.

In mammalian species, including man, the duration of myocardial contraction is shorter in atria than ventricles. Total contraction time depends at least in part on phosphorylation and dephosphorylation of cardiac regulatory proteins. Dephosphorylation reactions are mediated by protein phosphatases. In the mammalian heart more than 90% of the protein phosphatase (PP) activity consists of PP1 and PP2A. Therefore, the aim of this study was to investigate which isoforms of PP1 and PP2A are present in human myocardium and whether their expression is regionally different. RT-PCR and Northern blotting revealed that all isoforms of PP1 and PP2A presently known are expressed in the human heart. Expression levels of PP1 alpha, delta, and gamma as well as 2A alpha were higher in right ventricles than in right atria. However, there was no such difference for PP2A beta. At the protein level PP1 alpha was unchanged, whereas PP2A was by 56% higher in right ventricles compared to atria. The phosphorylation state of TnI was lower in right ventricle than in right atrium. Thus, lower protein expression of PP2A in atrium could contribute to the faster relaxation by increasing the phosphorylation state of TnI. We conclude that expression of PP1 and PP2A isoforms is regionally regulated in the human heart.

Blotting, Northern↗
PubMed2000

[Stable and unstable pertrochanteric femoral fractures. Differentiated indications for the dynamic hip screw].

The aim of all surgical procedures in the treatment of trochanteric fractures in elderly and even geriatric patients is achievement of initial stability. We examined in a clinical trial whether primary stability was achieved in all types of trochanteric fractures following osteosynthesis with the Dynamic Hip Screw (DHS). From 1994 to 1996, 122 patients with trochanteric fractures had osteosynthesis by dynamic hip screw. Patient records were evaluated and all data got registered with a standardized protocol;clinical radiological outcome was analysed after an average period of 1.9 years after injury according to the Traumatic Hip Rating Score. 22% of all patients died meantimes, 51.6% of the remaining 95 patients could get examined. The average age was 75.5 years, the patient population showed an increased preoperative morbidity (2.5 points) according to ASA-Score. 81% showed progressive osteoporosis. According to the AO-classification 47% stable fractures (type A-1) and 53% instable trochanteric fractures (type A-2 and A-3) occurred. Surgery lasted 77 minutes average in osteosynthesis of stable fractures. The duration of 108 minutes in instable fractures was significantly higher, as well as the blood loss was 43% increased in these complex fractures. Complications closely associated to the osteosynthesis appeared only in instable fractures (7%). Also common complications (24.6%) predominated with 15.6% in type A-2 and A-3 fractures versus 9% in type A-1 fractures; mortality was also different with 5.7% versus 1.6%. Assessment of the functional outcome according to THRS showed a significant deterioration of 20 points in 71% of all patients compared with the preoperative score. The results show that dynamic hip screw osteosynthesis in instable trochanteric fractures is associated to a higher incidence of complications. While the dynamic hip screw still represents the standard implant in stable fractures of the trochanteric region, being aware of improved intramedullary implants regarding biomechanical features and surgical technique, the results justify to critical consider the use of DHS for osteosynthesis in instable fractures of the trochanteric region.

Aged↗
PubMed2000

Prevention of osteoporosis in heart transplant recipients: a comparison of calcitriol with calcitonin and pamidronate.

Bone loss and osteoporotic fractures are common in cardiac transplant recipients. To compare two prophylactic medical regimens after heart transplantation, 26 consecutive heart transplant recipients were randomized to receive either continuous oral calcitriol (0.5 microg/day) combined with nasal salmon calcitonin (200 U/day) for the first 3 months (group A) or intermittent intravenous pamidronate (0.5 mg/kg body weight) every third month (group B). Bone mineral density (BMD) and biochemical indices of bone turnover were measured at baseline and 3, 6, 12, and 18 months after transplantation. The mean pretransplant BMD, measured by dual energy X-ray absorptiometry (DXA) was significantly lower in the patients compared with age-matched healthy controls. During the first year of treatment, rates of bone loss at the lumbar spine and femoral neck were slightly but significantly slower in the patients treated with pamidronate, but there was no longer a significant difference between the two groups after 18 months of heart transplantation. Irrespective of the mode of osteoporosis prevention, osteocalcin levels increased whereas urinary deoxypyridinoline decreased after transplantation, and significant bone loss was observed in both treatment groups. We found no relationship between initial BMD, markers of bone turnover, cumulative glucocorticoid dose, or cyclosporine levels and the rate of bone loss after cardiac transplantation. In summary, we found that the rapid and severe bone loss following heart transplantation could be attenuated by two preventive measures, pamidronate or calcitriol with calcitonin.

Absorptiometry, Photon↗
PubMed2000

Wound complications after left ventricular assist device implantation.

BACKGROUND: Wound necrosis and infection pose a tremendous risk for patients with left ventricular assist devices. METHODS: We analyzed our database of patients with left ventricular assist devices for those who developed wound dehiscence and concomitant infection after left ventricular assist device implantation. RESULTS: Three of our 66 patients (4.5%) with implantable ventricular assist devices had had severe wound complications with necrosis of the abdominal or thoracic wall uncovering part of the device. The predominant impact on the development of these complications was presumably related to multiple surgical interventions on the same site. CONCLUSIONS: Nevertheless, these patients can recover and undergo successful heart transplantation if adequately managed.

Abdominal Muscles↗
PubMed2000

Emergency coronary artery bypass grafting after failed coronary angioplasty: what has changed in a decade?

BACKGROUND: We assessed the impact of patient and procedural characteristics on the outcome after emergency coronary artery bypass grafting (CABG) for failed percutaneous transluminal coronary angioplasty (PTCA) and temporal changes in these factors. METHODS: Patients who underwent PTCA and subsequent emergency CABG were identified from the databases of the Departments of Cardiology and Cardiothoracic Surgery. RESULTS: Two periods of clinical practice were compared. In 1989 to 1993, 2,880 PTCAs were performed, 64 patients underwent emergency CABG (2.3%), and 7 patients died (10.9%). During 1994 to 1998, 46 patients of 3,801 PTCAs underwent emergency CABG (1.2%, p < 0.01), and 7 patients died (15.2%, NS). The average rate of stenting increased from 0.8% to 24% in 1994 to 1998 as well as the frequency of arterial bypass grafts (0% vs 39%). In the latter period, patients were older, were more often females, had more cardiovascular risk factors, a higher Cleveland score (each p < 0.05), and suffered more often from periprocedural myocardial infarctions (p < 0.001) and nonfatal periprocedural complications (p < 0.01). CONCLUSIONS: Although the frequency of emergency CABG after failed PTCA declined, perioperative mortality tended to increase according to an unfavorable shift in patient risk factors and morbidity.

Adult↗
PubMed2000

Preoperative immunoglobulin treatment in patients with Werlhof's disease undergoing cardiac operation.

BACKGROUND: Patients with Werlhof's disease and undergoing a cardiac surgical procedure with cardiopulmonary bypass are at increased risk for bleeding complications. We report the usefulness of preoperative immunoglobulin treatment in selected patients. METHODS: Between May 1995 and July 1998, 10 patients with Werlhof's disease underwent a cardiac surgical procedure with cardiopulmonary bypass in our department. Five patients with mean platelet counts of less than 80x10(9)/L received immunoglobulin therapy preoperatively (group 1). The other 5 patients with mean platelet counts higher than 80x10(9)/L were not so treated (group 2). RESULTS: In group 1, mean platelet count increased from 54x10(9)/L 5 days before operation to 112x10(9)/L after immunoglobulin treatment (p = 0.018) and did not fall to less than 60x10(9)/L postoperatively. Patients in group 1 received 16 units of packed red blood cells and 5 units of platelet concentrate. Patients in group 2 required 24 units of packed red blood cells, 5 units of platelet concentrate, and 23 units of fresh frozen plasma. Only 1 patient (group 2) had a surgical bleeding complication that required reexploration. Mean drainage loss was 1,100 mL in group 1 and 1,210 mL in group 2. CONCLUSIONS: Our data demonstrate that immunoglobulin treatment of patients with Werlhof's disease and mean platelet counts of less than 80x10(9)/L significantly augments platelet counts preoperatively. It may be useful in selected patients.

Adult↗
PubMed2000

Impact of malignant hematological disorders on cardiac surgery.

BACKGROUND: Patients suffering from malignant hematological disorders may be at increased risk, when undergoing cardiac surgery. We report on our experiences with ten cardiac procedures in nine patients (3 males, 6 females, 19-85 yr old, mean age 61 yr). METHODS AND RESULTS: There were two patients with Hodgkin's lymphoma and one patient each with Waldenstrom's syndrome, multiple myeloma, polycythemia, myelodysplasia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma and idiopathic aplastic anemia. Cardiac diseases included coronary artery disease in six, aortic stenosis in two, and mitral insufficiency in one patient. Consecutively, cardiac procedures were coronary artery bypass grafting in six, aortic valve replacement in two, and mitral valve replacement in one patient. No patient died. Postoperatively, one patient suffered from a pericardial tamponade requiring surgical removal and 5 months later from a prosthetic endocarditis necessitating change of the bioprosthesis. One patient developed a superficial wound infection, which was treated conservatively. Four patients received no blood products. Altogether, we transfused 32 packed red blood cells, seven units of fresh frozen plasma and 16 platelet concentrates. Total drainage loss was 883 ml (250-1510 ml). CONCLUSIONS: Cardiac surgery in patients suffering from malignant hematological disorders may be performed, but carries an increased morbidity. Therefore, indications for cardiac procedures must be carefully considered.

Adult↗