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Biomedical subjects

C Schmid

Publications and source records attributed to C Schmid.

At least 109 records · Page 6Linked to original sources
PubMed2000

Effect of high dose platelet inhibitor treatment on thromboembolism in Novacor patients.

BACKGROUND: Thromboembolism and bleeding are among the most hazardous complications following implantation of long-term left ventricular support systems. This report focuses on the effect of high dose platelet inhibitor treatment in patients with the Novacor system to prevent thromboembolic events. METHODS: Thirty-eight (out of 58) Novacor patients (43+/-11 years old) were studied in a non-randomized manner. Postimplantation: 20 patients were treated with heparin only (control group), whereas in the other 18 patients aspirin (3x330 mg/day) and dipyridamol (3x75 mg/day) were added to the treatment protocol (aspirin group). RESULTS: Age, body size, underlying heart disease and support interval were comparable among both groups, however, patients in the aspirin group were much sicker with regard to urgency status, postoperative right heart failure and hematologic disorders. Cerebral thromboembolic complications were lower in the aspirin group (33% of patients, 0.4+/-0.7 events) as compared to the control group (55% (P=0.18), 1.4+/-2.3 events (P=0. 048)). Non-cerebral thromboembolism of surgical relevance was rare. The incidence of bleeding complications was mildly increased in the aspirin group. CONCLUSION: The addition of high dose platelet inhibitors seems to lower the incidence of thromboembolism in Novacor patients.

Adult↗
PubMed2000

Are patients with Werlhof's disease at increased risk for bleeding complications when undergoing cardiac surgery?

BACKGROUND: It is generally assumed, that patients with Werlhof's disease (WD) are at increased risk for bleeding complications when undergoing cardiac surgery with extracorporeal circulation. Therefore we performed this case control study to estimate the real risk for bleeding complications of these patients. METHODS: Between 05/95 and 07/98, ten patients with WD (eight males, two females) underwent cardiac surgery employing extracorporeal circulation (WD-group). Five of these patients with platelet counts below 80/nl were treated by immunoglobulins preoperatively. Each patient with WD was matched to five patients without WD (no-WD-group) using diagnosis, age, gender, ejection fraction, number of distal anastomosis and body-mass-index as matching criteria. RESULTS: Mean number of platelet counts were significant lower in the WD-group than in the no-WD-group despite a significant increase of platelet counts after immunoglobulin treatment (54/nl-->112/nl, P=0.018). On the day before, directly after and on the first day after surgery they were 141/nl vs. 215/nl (P=0.012), 75/nl vs. 147/nl (P=0.001) and 93/nl vs. 136/nl (P=0.009). Accordingly, patients of the WD-group received significantly more platelet concentrates than patients of the no-WD-group (mean number of platelet concentrates: 2.3 versus 0.7, P=0.007). Total drainage loss via the mediastinal chest tubes was almost identical (1197 ml in the no-WD-group and 1140 ml in the WD-group). One patient of each group suffered from a bleeding complication requiring reexploration. Three patients of the no-WD-group (6%) and one patient of the WD-group (10%) expired postoperatively unrelated to WD. CONCLUSIONS: Patients with WD may possibly undergo cardiac surgery without a markedly enhanced risk for bleeding complications despite a more than usual transfusion requirement and significantly lower platelet counts perioperatively.

Adult↗
PubMed2000

Reversal of metallothionein expression is different throughout the human myocardium after prolonged left-ventricular mechanical support.

OBJECTIVES: We examined the distribution of metallothionein (MT), a stress-inducible protein, and the cardiomyocyte diameter in human hearts after left-ventricular assist device (LVAD) support. BACKGROUND: Remodeling in end-stage heart failure is characterized by myocyte hypertrophy and alterations of several inducible proteins. LVADs used as a bridge to cardiac transplantation unload the left ventricle and may lead to a reversal of the remodeling, but little is known about the pathophysiology of this process. METHODS: The immunoreactivity for MT and the cardiomyocyte diameter was analyzed in left-ventricular tissue specimens of 17 patients with end-stage heart failure before and after LVAD support. RESULTS: MT positive cells were mainly located sub-endocardially in vacuolized cardiomyocytes and in small vessels throughout the myocardium. During LVAD support, MT-positive myocytes decreased in the sub-endocardial (p < 0.008) and sub-epicardial region (p < 0.003), MT-positive vessels decreased similarly (p < 0.003). Cardiomyocyte diameter decreased significantly only in the sub-endocardium (p < 0.03). Hearts of patients supported longer than 88 days (= median) showed substantially lower MT reactivity at the time of LVAD explantation as compared to patients supported less than 88 days. CONCLUSION: Our results suggest that unloading of the left ventricle during prolonged LVAD support leads to regression of cellular hypertrophy and a decrease of MT expression. The preferential reduction of MT-positive vacuolized cardiomyocytes in the sub-endocardium is comparable with the concept of greatest reduction of wall stress in this area of the myocardium and may be due to the improvement of myocardial blood flow and the energy balance.

Adult↗
PubMed2000

Selection and management of ventricular assist device patients: the Muenster experience.

BACKGROUND: Because of the growing discrepancy between the availability of donor organs and the number of patients with end-stage heart disease who need heart transplantation, a larger proportion of patients waiting for a suitable donor heart require pre-operative mechanical circulatory assistance. The criteria for the selection and management of these patients as applied at Muenster University Hospital are reviewed. METHODS: The study population consists of 631 patients referred to our center for transplantation between January 1, 1990, and December 31, 1996. Two hundred ninety-seven patients were listed for transplantation and 157 were transplanted. Of 41 patients who underwent implantation of a ventricular assist device (n = 34, Novacor; n = 6, TCI HeartMate; n = 1, Medos), 39 received the device as a bridge to transplantation and 2 as permanent support. For the purpose of the analysis, the study population was divided into 3 groups (elective bridging, urgent bridging, emergency bridging) and compared with heart transplant candidates who did not require mechanical circulatory assistance. RESULTS: Patients who underwent elective or urgent assist-device implantation were younger and had greater hemodynamic compromise than the remainder of patients waiting for heart transplantation, as suggested by a higher functional class and lower mean arterial pressure, cardiac index, serum sodium, and pulmonary artery wedge pressure. Survival of patients who electively underwent implantation of an assist device was better than that of patients who were stable on the waiting list and did not undergo heart transplantation during follow-up. CONCLUSIONS: This finding suggests that earlier implantation of assist devices may facilitate resolution of organ dysfunction before heart transplantation.

Adult↗
PubMed2000

Kallmann's syndrome: clues to clinical diagnosis.

Hypogonadotropic patients may visit pediatricians, general practitioners, endocrinologists or urologists, presenting with microphallus, cryptochidism or pubertas tarda and delayed bone maturation. Congenital hypogonadotropic hypogonadism is characterized, apart from small testes, by the constellation of low serum levels of testosterone, LH and FSH. Kallman's syndrome is characterized by congenital hypogonadotropic hypogonadism with midline defects such as anosmia (a deficiency of the sense of smell). The first case report dates back to 1856, and genetic defects causing the syndrome have been recently described. The diagnosis can be clinically suspected and is established by confirming hormonal studies.

Adolescent↗
PubMed2000

Kallmann's syndrome: clues to clinical diagnosis.

Five cases of Kallmann's syndrome are presented, out-patients with microtestes, hypogonadotropic hypogonadism and complete anosmia. The final diagnosis was made only when they were aged between 17 and 26 (mean 21 years), although they had been seen by several physicians before: 3 for cryptorchidism and 3 for absence of spontaneous puberty; 2 had a positive family history, and 4 of the 5 patients or their parents admitted that they were aware of the fact that their sense of smell was completely absent, but they did not mention it spontaneously.

Adolescent↗
PubMed2000

Na+ translocation by complex I (NADH:quinone oxidoreductase) of Escherichia coli.

Following on from our previous discovery of Na+ pumping by the NADH:ubiquinone oxidoreductase (complex I) of Klebsiella pneumoniae, we show here that complex I from Escherichia coli is a Na+ pump as well. Our study object was the Escherichia coli mutant EP432, which lacks the Na+/H+ antiporter genes nhaA and nhaB and is therefore unable to grow on LB medium at elevated Na+ concentrations. During growth on mineral medium, the Na+ tolerance of E. coli EP432 was influenced by the organic substrate. NaCl up to 450 mM did not affect growth on glycerol and fumarate, but growth on glucose was inhibited. Correlated to the Na+ tolerance was an increased synthesis of complex I in the glycerol/fumarate medium. Inverted membrane vesicles catalysed respiratory Na+ uptake with NADH as electron donor. The sodium ion transport activity of vesicles from glycerol/fumarate-grown cells was 40 nmol mg-1 min-1 and was resistant to the uncoupler carbonyl-cyanide m-chlorophenylhydrazone (CCCP), but was inhibited by the complex I-specific inhibitor rotenone. With an E. coli mutant deficient in complex I, the Na+ transport activity was low (1-3 nmol mg-1 min-1), and rotenone was without effect.

Cell Membrane↗
PubMed2000

Galactorrhoea and pituitary mass: a typical prolactinoma?

A 21 year old woman presenting with galactorrhoea, hyperprolactinaemia, and a pituitary mass on magnetic resonance imaging (MRI) is described who was referred to us before planned pituitary surgery. Although a thorough history did not suggest hypothyroidism, laboratory studies revealed profound primary hypothyroidism. At that time, pituitary MRI showed homogeneous enlargement of the pituitary gland consistent with pituitary hyperplasia due to primary hypothyroidism. With thyroid hormone replacement therapy the galactorrhoea resolved, concentrations of prolactin and thyroid hormones returned to normal, and the pituitary shrunk to normal size within two months. This case illustrates that primary hypothyroidism can present only with galactorrhoea and pituitary mass, and should therefore be considered in the differential diagnosis of hyperprolactinaemia and pituitary enlargement.

Adult↗
PubMed2000

Changes in calcaneal trabecular bone structure after heart transplantation: an MR imaging study.

PURPOSE: To use high-spatial-resolution magnetic resonance (MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after heart transplantation and to compare this technique with bone mineral density (BMD) measurement in predicting therapy-induced bone loss and vertebral fracture status. MATERIALS AND METHODS: High-spatial-resolution 1.5-T MR imaging of the calcaneus was performed in 40 men 11-120 months after heart transplantation, in 11 men before heart transplantation, and in 10 age-matched male volunteers. Sagittal and transverse T1-weighted spin-echo images with a voxel size of 0.195 x 0.195 x 1.000 mm were obtained, and structure measurements analogous to bone histomorphometric values were calculated. In addition, the BMD of the lumbar spine was determined in the transplant recipients pre- and postoperatively by using quantitative computed tomography, and vertebral fracture status was assessed. RESULTS: Significant differences in structure and BMD measurements were found between patients before and after heart transplantation (P <. 05). In 17 (42%) of 40 transplant recipients, vertebral fractures were found. Although structure measurements were significantly different between patients with and those without fractures (P <.05), BMDs were not. Correlations between time after transplantation and some structure measurements were moderately significant (P <. 05), but such correlations with BMD measurements were not. CONCLUSION: MR imaging-derived structure measurements in the calcaneus are useful for monitoring bone changes after heart transplantation and assessing vertebral fracture status.

Adult↗
PubMed2000

Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use.

In recent years, analogs of human insulin have been engineered with the aim of improving therapy for people with diabetes. To ensure that the safety profile of the human hormone is not compromised by the molecular modifications, the toxico-pharmacological properties of insulin analogs should be carefully monitored. In this study, we compared the insulin and IGF-I receptor binding properties and metabolic and mitogenic potencies of insulin aspart (B28Asp human insulin), insulin lispro (B28Lys,B29Pro human insulin), insulin glargine (A21Gly,B31Arg,B32Arg human insulin), insulin detemir (NN304) [B29Lys(epsilon-tetradecanoyl), desB30 human insulin], and reference insulin analogs. Receptor affinities were measured using purified human receptors, insulin receptor dissociation rates were determined using Chinese hamster ovary cells overexpressing the human insulin receptor, metabolic potencies were evaluated using primary mouse adipocytes, and mitogenic potencies were determined in human osteosarcoma cells. Metabolic potencies correlated well with insulin receptor affinities. Mitogenic potencies in general correlated better with IGF-I receptor affinities than with insulin receptor off-rates. The 2 rapid-acting insulin analogs aspart and lispro resembled human insulin on all parameters, except for a slightly elevated IGF-I receptor affinity of lispro. In contrast, the 2 long-acting insulin analogs, glargine and detemir, differed significantly from human insulin. The combination of the B31B32diArg and A21Gly substitutions provided insulin glargine with a 6- to 8-fold increased IGF-I receptor affinity and mitogenic potency compared with human insulin. The attachment of a fatty acid chain to LysB29 provided insulin detemir with reduced receptor affinities and metabolic and mitogenic potencies but did not change the balance between mitogenic and metabolic potencies. The safety implications of the increased growth-stimulating potential of insulin glargine are unclear. The reduced in vitro potency of insulin detemir might explain why this analog is not as effective on a molar basis as human insulin in humans.

Adipocytes↗
PubMed1999

Ambulatory care of patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVAD) have revolutionized the treatment of patients with acute and chronic heart failure as they provide a high quality of life. We report on our experience with patients receiving ambulatory care after LVAD implantation. METHODS AND RESULTS: Since July 1995, 46 patients with a mean age of 45+/-11 years underwent implantation of an electrically driven LVAD with portable controller and batteries. Sixteen (35%) patients bridged >30 days were treated in part on an outpatient basis. After LVAD implantation, they were treated in the hospital for 86+/-32 days (range 40 to 153 days). Afterward, they received ambulatory care for 74+/-76 days (range 2 to 301 days, total experience 1206 days). In 13 cases, the outpatient treatment was interrupted by 1.7+/-1.7 readmissions, for a total of 32+/-42 days (median 19 days). Reasons for readmission included systemic or drive line infections (incidence 0.0066 per outpatient day), suspected or true thromboembolic events (incidence 0.0066 per outpatient day), and suspected malfunction of the LVAD. One patient supported as alternative to transplantation died after cerebral bleeding after 244 days, 1 patient with a history of acute myocarditis had ventricular fibrillation during LVAD assist while being at home for 177 days and died in a low output state, 10 patients were given transplantation after a mean support interval of 206+/-88 days, and 4 patients currently await heart transplantation. CONCLUSIONS: Outpatient treatment after LVAD implantation is feasible, and severe complications are uncommon.

Adult↗
PubMed1999

Mitogenic and antiapoptotic effects of insulin-like growth factor binding protein-6 in the human osteoblastic osteosarcoma cell line Saos-2/B-10.

Insulin-like growth factor (IGF) I is a potent mitogen for human osteosarcoma cells such as the Saos-2/B-10 cell line. IGF binding proteins (IGFBPs) prevent stimulation of DNA synthesis by IGFs. In contrast to recombinant human (rh) IGFBP-2, -3, -4, and -5, 10-100 nM rhIGFBP-6 stimulated [(3)H]thymidine incorporation into DNA and multiplication of Saos-2/B-10 cells. Upon withdrawal of serum, 30 nM IGFBP-6 also decreased apoptosis (within 4 h) and increased protein content and sodium-dependent phosphate uptake (within 24 h), but less potently than IGF I. (125)I-labeled rhIGFBP-6 did not bind to the cells, and cold IGFBP-6 did not affect (125)I-labeled IGF I binding. Production of IGF I, IGF II, and IGFBP-6 by the cells or significant degradation of rhIGFBP-6 could not be detected within 24 h of incubation. Thus, among the rhIGFBPs tested, rhIGFBP-6 is unique in stimulating osteosarcoma cell growth. Furthermore, it has an antiapoptotic effect.

Alkaline Phosphatase↗
PubMed1999

[Cushing syndrome due to ectopic ACTH secretion: an uncommon case presentation, diagnosis and therapy].

Ectopic ACTH secretion due to malignant tumours is the most frequently underdiagnosed form of Cushing's syndrome. The majority of neoplasms causing ectopic ACTH syndrome are small-cell cancers of the lung or carcinoids. Other well-documented cases include adenocarcinoma of the lung, medullary thyroid carcinoma, pancreatic islet tumours and malignant thymoma. We report a rare case of metastatic colonic adenocarcinoma with ectopic ACTH syndrome. Clinical features such as proximal muscle weakness, peripheral oedema, hypertension or hirsutism in women, or the presence of unexplained hyperglycaemia, hypokalaemia or metabolic alkalosis in patients with known malignancy strongly suggest ectopic ACTH syndrome. Removal of the source of ACTH is the treatment of first choice, but often not feasible. Most often, treatment modalities are only palliative, with drugs directed against hypercortisolism such as aminoglutethimide, metyrapone, ketoconazole or mifepristone.

ACTH Syndrome, Ectopic↗
PubMed1999

Cutting edge: receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells.

Immunization with heat shock proteins (HSPs) induces Ag-specific CTL responses. The specificity of the immune response is based on peptides associated with HSPs. To investigate how exogenous HSP/peptide complexes gain access to the MHC class I-restricted Ag presentation pathway, we incubated the monocytic cell line P388D1 and the dendritic cell line D2SC/1 with gold-labeled HSPs gp96 and HSC70. We show that HSPs bind specifically to the surface of these APCs and are internalized spontaneously by receptor-mediated endocytosis, demonstrating the existence of specific receptors for HSPs on these cells. In addition, we observe colocalization of internalized HSPs and surface MHC class I molecules in early and late endosomal structures. These findings provide possible explanations for the immunogenicity of HSP/peptide complexes and for the transfer of HSP-associated peptides onto MHC class I molecules.

Animals↗
PubMed1999

Drug resistance in Sudanese Trypanosoma evansi.

The drug sensitivities of 16 Trypanosoma evansi isolates from Sudan were examined using two different in vitro assays and rodent models. IC50 values (concentration which inhibited incorporation of 3H-hypoxanthine by 50%) obtained in a 40 h assay indicate that most of the isolates were resistant to suramin, a drug which has not been used in Sudan since 1975. Sensitivities for suramin in a 10-day-in vitro assay varied within a 124-fold range. The in vitro results were confirmed by infection/treatment experiments in mice. Sensitivities in vitro for quinapyramine varied within a 166-fold range. In mice, the least sensitive isolates were not cured with dosages up to 10 mg/kg quinapyramine. Based on in vitro results, all isolates appeared to be susceptible to isometamidium.

Animals↗
PubMed1999

Extent of margin positivity as a predictor for local recurrence after breast conserving irradiation.

The extent of positivity of the final excision margin in relationship to other relevant factors was evaluated as a predictor for local recurrence after breast conservation therapy (BCT). As part of an institutional practice policy for BCT in 509 stage I/II breast carcinomas, 105 cases had a final excision margin, which was positive. The median age for this cohort was 58 years and the median follow-up was 86 months. All positive margin patients received whole breast irradiation to 50 Gy-50.4 Gy followed by a boost to the tumor bed for an additional 20 Gy. The extent of positivity (EOP) of the excision margin was graded according to a four-point scale: focal, minimal, moderate, extensive. Cases were then analyzed for local failure according to EOP grade, histology, age, tumor size, total excision volume, re-excision, tamoxifen therapy, and chemotherapy. A focal or minimal EOP grade was found in 70% of specimens while an additional 26% were moderate or extensive. The incidence of invasive carcinoma with prominently associated DCIS was significantly greater in cases with an EOP grade of moderate/extensive. There were nine ipsilateral breast recurrences, eight of which could be evaluated for EOP grade. All recurrences were in or near the previous biopsy cavity. A Kaplan-Meier plot of freedom from local failure showed a significant (P = 0.008) difference between cases grouped by EOP grade of focal/minimal as compared to moderate/extensive. A Cox proportional hazards regression model found that the only variable significantly related at the P < or = 0.05 level to local failure was an EOP grade of moderate/extensive. For breast excision specimens with a positive final margin, an EOP grade of moderate/extensive is a predictor for local recurrence after BCT, which may be independent of other variables such as age or histology.

Adult↗
PubMed1999

Impact of local donor and regionalization on a German transplantation center. UNI NRW. Universities of North Rhine Westfalia.

Optimal allocation of donor organs is an ongoing matter of debate. We report on the impact of the foundation of UNI NRW, a close transplant collaboration of seven university centers with the intention of improving donor organ allocation, on the heart transplant program in Münster. All donor organs retrieved were offered first to the patients within this region before going into the Eurotransplant (ET) Foundation pool. The heart transplant program data were prospectively (for 1997) and retrospectively (for 1996) analyzed with regard to donor organ availability and allocation. There was a slight decrease in the number of donor hearts offered and accepted within the UNI NRW region in 1997 as compared to in 1996. However, due to the significantly lower organ export rate, the number of heart transplantations performed in UNI NRW rose from 47 to 72 procedures. In Münster, only six donor organs (16%) were procured from outside UNI NRW in 1997, and these were, in part, due to special urgency requests. In conclusion, the institutionalization of UNI NRW within the framework of ET offers more flexibility, decreases total ischemic time, and may help to lower costs.

Europe↗