PubMed Health⌕ Search

Biomedical subjects

Alice Schmidt

Publications and source records attributed to Alice Schmidt.

7 recordsLinked to original sources
PubMed2004

Normal regulation of elevated plasma ghrelin concentrations in dialysis patients.

BACKGROUND: Chronic renal failure is often associated with malnutrition, and malnourished patients are subject to increased morbidity and mortality. Therefore plasma concentrations of the stomach-derived peptide hormone ghrelin, which has been shown to exert potent GH-releasing and appetite-stimulating effects, were determined and correlated with nutritional parameters. METHODS: Twenty-four patients (15 male, 9 female) undergoing hemodialysis (HD) were studied. In addition, six patients were studied before and one hour after ingestion of a meal and five were studied immediately before and at the end of the dialysis session. RESULTS: Chronic renal insufficiency was associated with significantly elevated ghrelin levels (320.1 +/- 57 fmol/mL vs. 75.6 +/- 12.4 fmol/mL in controls; p < 0.007). Plasma ghrelin concentrations were also significantly higher in the 16 normal-weight patients than in the eight overweight or obese patients (399.6 +/- 76.3 fmol/mL vs. 161.1 +/- 41.3 fmol/mL; p < 0.03). Ingestion of food induced a decrease in five out of six patients tested (mean 242.3 +/- 66.5 fmol/mL vs. 186 +/- 30.7 fmol/mL; n.s.). HD also resulted in a significant decrease of elevated ghrelin concentrations: ghrelin was in the normal range at the end of HD in four of the five patients tested. Plasma ghrelin concentrations did not correlate with nutritional parameters except for cholinesterase which was negatively correlated to ghrelin. CONCLUSION: Plasma ghrelin concentrations are elevated in HD. The fact that ghrelin concentrations are higher in normal-weight than in overweight or obese HD patients and suppressed after ingestion of a meal suggests that the regulation of ghrelin release is retained in HD patients, albeit shifted to a higher level.

Adult↗
PubMed2003

Effects of ximelagatran, an oral direct thrombin inhibitor, r-hirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects.

OBJECTIVES: The effects of ximelagatran, an oral direct thrombin inhibitor (DTI), recombinant hirudin (r-hirudin) and enoxaparin on thrombin generation and platelet activation were studied in humans. BACKGROUND: Recombinant hirudin (parenteral DTI) and enoxaparin (low molecular weight heparin) have been demonstrated to be clinically effective in acute coronary syndromes. Ximelagatran is currently under investigation for the prevention and treatment of thromboembolism. The shed blood model allows for the study of thrombin generation and platelet activation in humans in vivo. METHODS: This was an open-label, parallel-group study involving 120 healthy male volunteers randomized to receive one of three oral doses of ximelagatran (15, 30 or 60 mg), r-hirudin (intravenous) or enoxaparin (subcutaneous) at doses demonstrated to be clinically effective in acute coronary syndromes, or to serve as a control. Thrombin generation (prothrombin fragment 1+2 [F1+2] and thrombin-antithrombin complex [TAT]) and platelet activation (beta-thromboglobulin [beta-TG]) biomarkers were studied using a shed blood model involving blood collection from skin incisions made using standardized bleeding time devices. RESULTS: Oral ximelagatran, intravenous r-hirudin and subcutaneous enoxaparin rapidly and significantly (p < 0.05) decreased F1+2, TAT and beta-TG levels in shed blood, indicating inhibition of thrombin generation and platelet activation. Statistically significant concentration (melagatran, the active form of ximelagatran)-response relationships for F1+2 (p = 0.005), TAT (p = 0.005) and beta-TG (p < 0.001) levels, with IC(50)s of 0.376 (F1+2), 0.163 (TAT) and 0.115 (beta-TG) micromol/l, were detected. Melagatran showed dose-proportional pharmacokinetics with low variability. All drugs were well tolerated. CONCLUSIONS: Oral administration of the DTI ximelagatran resulted in a rapid inhibition of both thrombin generation and platelet activation in a concentration-dependent manner using a human shed blood model. The inhibition of thrombin generation by 60 mg ximelagatran was comparable to that observed with doses of r-hirudin and enoxaparin demonstrated to be effective for the treatment of acute coronary syndromes.

Administration, Oral↗
PubMed2003

One-year growth hormone therapy improves granulocyte function without major effects on nutritional and anthropometric parameters in malnourished hemodialysis patients.

BACKGROUND/AIMS: Growth hormone (GH) resistance leads to enhanced protein catabolism and contributes to the malnutrition of patients with chronic renal failure (CRF). In short-term trials anabolic effects of rhGH therapy have been demonstrated in patients on chronic hemodialysis. METHODS: This study was initiated to determine the effects of 12 months of rhGH therapy on polymorphonuclear leukocyte (PMNL) function as well as on nutritional and anthropometric parameters. 0.125 IU/kg rhGH was given 3 times a week during the first 4 weeks and 0.25 IU/kg thereafter to 19 malnourished hemodialysis patients with a mean age of 59.3 +/- 13.4 years. RESULTS: Insulin-like growth factor I (IGF-I) concentrations rose significantly from 169.2 +/- 95.6 to 262.9 +/- 144.4 ng/ml (p < 0.01) in the first 3 months, but declined thereafter. Phagocytic activity of PMNLs also increased significantly in response to rhGH therapy and this activation remained stable over the whole 12-month period. Other parameters of PMNL function were not influenced by rhGH therapy. In addition, nutritional parameters such as albumin, prealbumin, transferrin, cholesterol, HDL-cholesterol, cholinesterase, predialytic creatinine and blood urea nitrogen were not affected by rhGH therapy. A decline of total body fat (TBF) was observed after 3 and 9 months of rhGH therapy (17.5 +/- 10 vs. 16.7 +/- 10% after 3 months, p < 0.017 and 16.8 +/- 8.7% after 9 months, p < 0.049), whereas lean body mass remained stable. CONCLUSIONS: Twelve months of rhGH therapy caused a significant increase in IGF-I levels, stimulated phagocytic activity of PMNLs and induced a decline of TBF. Other anthropometric and nutritional parameters were not affected, which might be related to the persistence of GH resistance.

Anthropometry↗
PubMed2002

Regular physical exercise improves endothelial function in heart transplant recipients.

BACKGROUND: Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease. METHODS: Male HTX patients and healthy, age-matched controls were studied. Seven HTX patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX) maintained a sedentary lifestyle without regular physical exercise since transplantation. A healthy control group comprised six subjects (age: 62 +/- 6 yr). Vascular function was assessed by flow-mediated dilation of the brachial artery (FMD). Systemic haemodynamic responses to intravenous infusion of the endothelium independent vasodilator sodium nitroprusside (SNP) and to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide synthase, were also measured. RESULTS: Resting heart rate was significantly lower (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/- 11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also tended to be lower in healthy subjects and in the training HTX patients. FMD was significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/- 0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p < 0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy controls and heart rate response to SNP was also impaired in sedentary HTX patients. DISCUSSION: Regular aerobic physical training restores vascular function in HTX patients, who are at considerable risk for developing vascular complications. This effect is demonstrable in conduit and systemic resistance arteries.

Blood Pressure↗
PubMed2002

Renal hemodynamic effects of somatostatin are not related to inhibition of endogenous insulin release.

BACKGROUND: Somatostatin inhibits endocrine and exocrine secretions and exerts renal vasoconstriction. The mechanism underlying somatostatin's vascular effects is unknown. Since insulin can cause vasodilation, we hypothesized that removal of basal insulin release by somatostatin may contribute to somatostatin-induced renal vasoconstriction. METHODS: The study was conducted in different protocols comprising forty-six healthy male volunteers. Randomized studies were performed to compare the effects of somatostatin alone (0.1 microg/kg/min) to the effects of somatostatin + low dose insulin (0.1 mU/kg/min), the effects of somatostatin + low dose insulin to the effects of somatostatin + high dose insulin (1.5 mU/kg/min), and the effects of insulin (1.5 mU/kg/min) + somatostatin. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured with the para-aminohippurate (PAH) and the inulin clearance technique, respectively. Blood pressure and pulse rate were measured non-invasively. RESULTS: Somatostatin alone decreased GFR (-14 +/- 6%, P < 0.001) and RPF (-16 +/- 7%, P < 0.001) whereas systemic hemodynamics were unchanged. Preceding or concomitant infusion of insulin at high doses (insulin plasma concentration of 127 +/- 25 or 144 +/- 17 microU/mL) but not co-infusion with low dose insulin (insulin plasma concentration of 11 +/- 3 microU/mL) mitigated or reversed the vasoconstrictive actions of somatostatin on GFR and RPF. CONCLUSIONS: Somatostatin induces marked renal vasoconstriction and exogenous restoration of fasting insulin concentrations does not influence the renal vascular effects. Therefore, it is unlikely that somatostatin-induced vasoconstriction is due to removal of basal insulin. Plasma insulin concentrations in the high postprandial range can reverse somatostatin-induced renal vasoconstriction, suggesting functional antagonism.

Adult↗
PubMedDate not supplied

Effects of 12 months of recombinant growth hormone therapy on parameters of bone metabolism and bone mineral density in patients on chronic hemodialysis.

BACKGROUND: Renal osteodystrophy is common in patients with chronic renal failure (CRF) on hemodialysis (HD), leading to reduced bone mineral density (BMD) and higher bone fracture incidences. Since growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are known to enhance bone metabolism and BMD, and CRF patients exhibit GH and IGF-1 resistance, recombinant human GH (rhGH) therapy could be beneficial for these patients. METHODS: This study evaluated the effects of a 12-month rhGH therapy on bone metabolism parameters; alkaline phosphatase (AP), osteocalcin (OC), procollagen I carboxyterminal propeptide (PICP), telopeptide ICTP, serum crosslaps, n-terminal propeptide of type III procollagen (PIIINP) and intact parathyroid hormone (iPTH), as well as on BMD of the lumbar spine and the femoral neck in 19 malnourished HD patients (10 females, 9 males) with a mean age of 59.3 +/- 13.4 yrs. Fourteen patients completed the 12-month study. RhGH (0.25 IU/kg) was given subcutaneously 3x/week after each dialysis session. RESULTS: IGF-1 concentrations rose significantly from 169.2 +/- 95.6 to 262.9 +/- 144.4 ng/mL (p<0.01) after 3 months, followed by a slight decline over the next 9 months. PICP as a bone formation marker significantly increased after 3 months from 250.1 +/- 112.6 to 478.5 +/- 235.2 ug/L (p<0.01), as well as PIIINP, whereas OC and bone resorption parameters like ICTP showed only a slight increase (ICTP: 50.3 +/- 18.5 to 70.0 +/- 39.5 ug/L after 3 months (ns)). All bone metabolism parameters slightly declined in the following 9 months, but remained above baseline values after 12 months. PTH rose from 198.0 +/- 139.2 to 456.0 +/- 268.7 ng/ml, p<0.01 after 6 months. BMD of the lumbar spine showed a significant reduction after 3-month rhGH therapy (0.80 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, p<0.01), but returned to baseline values after 12 months. BMD of the femoral neck remained stable during the entire study. CONCLUSIONS: In summary, 12-month rhGH treatment in patients on chronic HD caused a significant increase in IGF-1, together with an increase in bone turnover. In addition, there was a temporary reduction in BMD of the lumbar spine seen, which returned to baseline values after 12 months.

Absorptiometry, Photon↗