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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 325 records · Page 18Linked to original sources
PubMed1996

Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady state concentrations of GH in plasma.

To evaluate the principal determinants of the MCR and plasma t1/2 of unbound (free) GH in man, we performed steady state infusions of 3 doses of recombinant human GH during pharmacological suppression (iv octreotide) of endogenous GH secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH (measured by immunoradiometric assay) and GH-binding protein activity (radioligand assay). The MCR of free GH was determined from free plasma GH and the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the concentration and the in vivo dissociation constant (Kd) of GH-binding protein (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2 increased significantly with increasing plasma GH concentrations. The MCR of free GH over its physiological concentration range was positively correlated with the body mass index as a measure of relative obesity and negatively related to age, but only at supraphysiological GH concentrations. In the adult patients with CRF, the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2 was increased by 80-170%. Children with CRF showed a significantly lower MCR and higher t1/2 of plasma free GH than adult patients. Modeling and direct measurements of the off-rate of GH from its high affinity GHBP indicated normal dissociation rate constants but decreased molar concentrations of the GHBP in uremic plasma. We conclude that the rate of elimination of free GH from plasma in man is controlled by 1) plasma total free GH concentrations, 2) relative obesity, and 3) renal function within the physiological GH concentration range, whereas 4) age is a negative predictor of MCR only at supraphysiological GH concentrations.

Adolescent↗
PubMed1996

Control of pulsatile and tonic parathyroid hormone secretion by ionized calcium.

To investigate the effect of changes in ionized calcium on instantaneous PTH secretion, we examined seven young healthy volunteers by 1-min blood sampling under conditions of normo-, hypo-, and hypercalcemia. After a baseline period of 75 min, ambient ionized calcium was either increased or decreased by 0.2 mmol/L for 105 min by clamped infusion of calcium gluconate or sodium citrate. The characteristics of PTH secretion were analyzed by a deconvolution technique, accounting for subject-specific plasma PTH disappearance half-life, as measured during the first 15 min of calcium infusion (range, 2.04-2.93 min). The process regularity of pulsatile PTH secretion was evaluated by an approximate entropy statistic. Under baseline conditions, 32% of total PTH secretion was released in a pulsatile fashion, with a burst frequency of 6.9 +/- 0.8 h-1 and a PTH mass per burst of 2.6 +/- 0.9 pmol/L. The remaining 68% of total secretion was attributed to tonic hormone release. During the initial 30 min of induced hypocalcemia, pulsatile secretion increased by 1140%, whereas tonic secretion did not change. The preferential increase in pulsatile PTH secretion was mediated by a combined rise in burst frequency and mass released per burst. During subsequent steady state hypocalcemia, the tonic secretion rate increased (255% of baseline), whereas burst frequency and burst mass decreased (to 103% and 189% of the baseline values), restoring the baseline ratio of tonic to pulsatile PTH secretion. The regularity of PTH release increased during steady state hypocalcemia. During hypercalcemia, tonic secretion, burst mass, and burst frequency decreased by 75%, 82%, and 32%, respectively, and remained constant throughout the clamp period. We conclude that acute hypocalcemia elicits an immediate pulsatile and a delayed tonic secretory response of the parathyroid gland with increased regularity of PTH release. Acute hypercalcemia suppresses both the pulsatile and the tonic component of PTH secretion.

Adult↗
PubMed1996

Renal findings in patients with short-term type 2 diabetes.

Under semiambulatory conditions, 85 consecutive patients with the diagnosis of Type 2 diabetes of short duration (excluding patients with islet cell antibodies or maturity onset diabetes of the young) were admitted to a self-control training program and were examined in this study. A comprehensive renal assessment was performed, including evaluation of albumin excretion rate (AER), renal hemodynamics, blood pressure (BP) profile, and indicators of genetic risk. AER > or = 30 mg/24 h was found in 13 (15%) of patients; in two of these patients, AER was > or = 300 mg/24 h. By logistic regression, high HbA1, current smoking, and BP parameters were significantly correlated with an increased risk of microalbuminuria (MA). In a multiple linear regression model, accounting for 57% of total variance, HbA1, ERPF, and current smoking were significantly correlated with AER. Median GFR (Cin(inulin clearance) 136 mL/min per 1.73m2; range, 94 to 194) and ERPF (Cpah(para-aminohippuric acid clearance) 733; range, 451 to 1328) were significantly higher in patients than in control subjects (upper 95th percentile, 131 and 706 mL/min per 1.73m2, respectively). In a multiple linear regression model, explaining 27% of total variance, age, AER, gender, and fasting blood glucose were significantly correlated to GFR. According to the criteria of average daytime BP > or = 135/85 mm Hg or 24-h BP > or = 130/80 mm Hg, 60% of patients were hypertensive (HT). Sixty-one percent of all patients (including 50% of the untreated normotensive patients) were "nondippers", i.e., < 15% nighttime decrease of mean arterial pressure. Either HT or nondipping was found in 79% of all patients, so that only 21% had a completely normal blood pressure profile. Ninety-four percent of untreated hypertensive patients had no MA. First-degree relatives of patients with MA compared with patients without MA had more frequent cardiovascular events (69% versus 31%). The risk of MA in diabetic patients with positive family history was amplified by poor glycemic control. MA, but not hypertension, was marginally related to K(m) of Na+/Li+ countertransport. It was concluded that (1) microalbuminuria is found in 15% of patients newly presenting with Type 2 diabetes; (2) a high proportion of patients exhibit hyperfiltration; (3) according to ambulatory BP only, 21% of patients have a completely normal circadian BP profile; (4) a family history of cardiovascular events interacts with glycemic control to increase the risk of MA.

Adult↗
PubMed1996

Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine.

In experimental renal failure, increased intramyocardial arteriolar wall thickness, reduced myocardial capillary density, and increased cardiac interstitium are found. The extent to which such alterations can be modified by therapeutic interventions has not been investigated to date. The purpose of this study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk. After perfusion fixation, heart and aorta were examined by stereological techniques. Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three interventions. In contrast, the wall thickness of intramyocardial arterioles was significantly higher in SNX; this was prevented by Ramipril and Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (Lv) was significantly lower and interstitial volume density (Vv) significantly higher in untreated SNX. Reduction of capillary length density was completely prevented by Moxonidine and in part by Ramipril. The increase in cardiac interstitial volume density was completely prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine treatment. The following conclusions can be drawn from the results: (1) all agents normalize aortic wall thickness, but only calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar wall thickening: (2) intramyocardial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the blood pressure to subnormal levels; i.e., changes in systemic blood pressure cannot completely explain the altered vascular structure in renal failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not completely accounted for by their hemodynamic actions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Influence of specific and non-specific endothelin receptor antagonists on renal morphology in rats with surgical renal ablation.

BACKGROUND: Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ETAR and ETA/ETBR antagonists. STUDY DESIGN: 5/6 subtotal nephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ETAR antagonist BMS 182874 (30 mg/kg/day) and ETAR/ETBR antagonist Ro 46-2005 (30 mg/kg/day) by gavage. Duration of the experiment eight weeks. METHODS: Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ETA/ETBR by quantitative PCR. RESULTS: SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with BMS 182874 (153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to sham operated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), BMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of BMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ETAR and ETBR mRNA were significantly lower. CONCLUSION: Both specific (ETAR) and non-specific (ETA/ETBR) endothelin antagonists interfere with development of glomerulosclerosis by mechanisms which are, at least in part, independent of systemic blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effect of ramipril, nifedipine, and moxonidine on glomerular morphology and podocyte structure in experimental renal failure.

BACKGROUND: Experimental renal failure causes structural alterations of the kidney. It is still unresolved how these changes are modified by antihypertensive treatment. Purpose of the study. To examine the effects of different antihypertensive agents (ramipril, nifedipine, moxonidine) mainly on glomerular geometry, cell number, cell morphology, and capillarization, in a subtotal nephrectomy model of renal failure. MATERIAL AND METHODS: Sham-operated male SD rats and subtotally nephrectomized (SNX) ad libitum-fed rats were examined. Groups of 8-10 SNX rats were left untreated or were treated with ramipril (0.5 mg/kg b.w. per day), nifedipine (20 mg/kg b.w. per day) or moxonidine (10 mg/kg b.w.per day) respectively. After perfusion fixation the kidneys were examined using stereological techniques. RESULTS: Systolic blood pressure (by tail plethysmography) was 110+/-13 mm Hg in sham-op and 119+/-9 in SNX. It was effectively and comparably reduced below normal values by ramipril (89+/-11 mmHg), nifedipine (98+/-23 mmHg) and moxonidine (92+/-11 mmHg). The glomerulosclerosis index (SI) was significantly increased in SNX versus sham-op; it was similarly decreased by ramipril and moxonidine but less so by nifedipine. Vascular damage (preglomerular vessels) was reduced by all treatments whereas tubulointerstitial damage was signficantly reduced only by ramipril and moxonidine. Mean glomerular tuft volume was increased in SNX compared to sham-op. controls and was normalized only by ramipril treatment. Glomerular cells were differentially affected the three antihypertensive agents. After subtotal nephrectomy an increase in podocyte volume and mesangial cell number per glomerulus was noted. Nifedipine, and to a lesser extent ramipril, prevented mesangial cell hyperplasia. In contrast, only the ACE inhibitor ramipril, but not nifedipine or moxonidine prevented podocyte abnormalities, particularly podocyte hypertrophy. CONCLUSIONS: (i) Despite comparable reduction in systolic blood pressure, different classes of antihypertensive agents had diverse effects on renal damage in subtotally nephrectomized rat. This observation is consistent with specific, non-hemodynamic actions of anti-hypertensives. (ii) Glomerular and tubulointerstitial damage are prevented by treatment with ACE inhibitors and antisympathotonic agents, but not with the calcium antagonist nifedipine. In contrast, renal vascular changes were also prevented by nifedipine. (iii) Only ACE inhibitors effectively inhibited podocyte hypertrophy and mesangial cell hyperplasia. Whether the superior effect of ACE inhibitors on glomerulosclerosis is related to inhibition of glomerular growth and podocyte hypertrophy as well as preservation of podocyte structure, or whether these findings are merely a passive reflection of greater efficacy, remains unresolved.

Animals↗
PubMed1996

Why are lipids not predictive of cardiovascular death in the dialysis patient?

The rate of cardiovascular death, and specifically of cardiac death, in dialysis patient is excessive and comparable to that in the high-risk group of survivors of myocardial infarction. Yet, in patients on dialysis total cholesterol, LDL cholesterol, apolipoprotein B and other indicators of coronary risk--with the exception of lipoprotein(a)--are consistently higher in survivors than in those dying from cardiovascular causes, but at least in diabetic patients on dialysis, an extremely high-risk population, lipids are predictive of cardiac death. Malnutrition as a confounding factor might explain the inverse relation between lipid indicators and cardiac death in nondiabetic patients. Indirect arguments can be marshalled that malnutrition increases cardiac death as a consequence of low L-arginine levels and the ensuing diminished synthesis of NO.

Apolipoproteins B↗
PubMed1996

Prescription of calcium concentration and PTH control.

The use of calcium-containing oral phosphate binders, introduced in an effort to avoid aluminum-containing compounds, had led to more frequent episodes of hypercalcemia. This prompted the introduction of continuous ambulatory peritoneal dialysis (CAPD) solutions with diminished calcium content. The problems raised by such solutions included stimulation of parathyroid hormone (PTH) secretion and long-term maintenance of calcium balance. Some of these issues can today be answered on the basis of controlled prospective trials. Variability of the rate of intestinal calcium uptake of bone turnover, of baseline parathyroid activity, and other factors make it necessary to individualize the indication for the use of CAPD solutions with low calcium content.

Calcium↗
PubMed1996

Plasma thrombomodulin: a marker for microvascular complications in diabetes mellitus.

Thrombomodulin (TM), a marker of endothelial cell damage was studied in 183 patients with diabetes mellitus and different stages of complications. Thrombomodulin plasma levels correlated with duration of diabetes in patients with type I and type II diabetes. Thrombomodulin levels were higher in patients with increasing numbers of complications (nephropathy, retinopathy, arterio-occlusive disease, neuropathy). Neither the presence of retinopathy, nor neuropathy alone significantly increased plasma thrombomodulin in patients with similar urinary albumin concentration. The plasma level of thrombomodulin was more prominent in hypertensive than normotensive patients. Multivariate analysis showed that albuminuria is the factor which influences the most the increase of thrombomodulin in serum of diabetic patients.

Adult↗
PubMed1996

Angiotensinogen gene M235T polymorphism is not associated with diabetic nephropathy. The Diabetic Nephropathy Study Group.

BACKGROUND: There is agreement that a family history of hypertension (HT), is a predictor for the risk of diabetic nephropathy (DN) in patients with type 2 diabetes, and possibly also type 1 diabetes. It follows that genes related to the risk of hypertension must also be considered candidate genes for DN. The 235T allele of the angiotensinogen gene was found to be related to primary HT. METHODS: To examine whether it is predictive for DN as well, we examined the angiotensinogen gene polymorphism in 230 healthy local controls, 423 patients with type 1 diabetes (n = 180 with DN; n = 243 without DN) and 663 patients with type 2 diabetes (n = 310 with DN; n = 353 without DN). The angiotensinogen gene M235T polymorphism was determined using PCR amplification. RESULTS: The following results were obtained (i) no significant difference of genotype distribution (type 1: MM/MT/TT (%) 27.6/57.2/15.2 vs 27.2/56.1/16.7 (P = 0.92); type 2; MM/MT/TT (%) 31.7/48.2/2/20.1 vs. 32.9/46.8/20.3 (P = 0.93) or allele frequencies (type 1: M 0.56 vs. 0.55 (P = 0.795); type 2; M 0.56 vs. 0.56 (P = 0.86)) was found, between diabetic patients with or without DN, (ii) no difference was found between normotensive and hypertensive diabetic patients. CONCLUSION: The data argue against a role of the angiotensinogen gene M235T polymorphism in the manifestation of diabetic nephropathy or hypertension in diabetic patients.

Adult↗
PubMed1996

[Diuretics in renal failure].

The indications for the use of diuretics in patients with renal failure are edema and hypertension. An ancillary measure is dietary sodium restriction which permits reduction of the diuretic dose and reduces the frequency of diuretic induced side effects. The natriuretic action of diuretics is attenuated in renal failure both for pharmacokinetic and pharmacodynamic reasons. The most important cause for reduced efficacy of diuretics in renal patients is binding of diuretics to proteins within the tubular lumen so that the absolute free concentration of diuretics is diminished. Further important reasons for the diminished increment in urinary sodium excretion that is seen in patients with renal failure include a) reduced number of nephrons (i.e. reduced functional mass) and b) intrarenal compensatory mechanisms which increase sodium activity and tubular reabsorption of sodium. These difficulties can be overcome by dietary sodium restriction, by selection of higher doses of diuretics, by selection of appropriate intervals of administration and by combination of loop diuretics and thiasides. In order to recognize side effects resulting from excessive diuresis with hypovolemia and increase of serum creatinine concentration from prerenal causes it is necessary to closely monitor the patients.

Antihypertensive Agents↗
PubMed1996

Acute failure of the transplanted kidney--pathophysiology, diagnosis and prevention.

Acute failure of the transplanted kidney is a major problem in the early posttransplant phase and is recognized as a major cause of graft loss. Early renal transplant dysfunction is mainly due to ischemic damage (acute tubular necrosis), rejection, infection, and cyclosporin A toxicity. Less common causes include bleeding, ureteral obstruction, urinary leak, venous thrombosis, and stenosis or occlusion of the renal transplant artery. Recent advances in both invasive (renal biopsy) and non-invasive (imaging and biochemical) techniques have improved specificity and sensitivity of the diagnosis of the acute renal failure. Several procedures which aim to prevent the kidney transplant failure have recently been introduced. Although they were shown to reduce the incidence of early allograft failure, their influence on the long-term graft survival remains to be proven.

Acute Disease↗