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Biomedical subjects

R Krapf

Publications and source records attributed to R Krapf.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new cause of growth hormone insensitivity in humans.

The effects of metabolic acidosis on growth hormone and IGF-1 are poorly understood. We investigated the effects of chronic metabolic acidosis (induced by administration on NH4Cl, 4.2 mmol/kg body wt/day) on the growth hormone/IGF-1 endocrine axis in 6 normal male volunteers during metabolic balance conditions. NH4Cl administration resulted in hyperchloremic metabolic acidosis with plasma bicarbonate decreasing from 25 +/- 0.4 to 15.5 +/- 0.9 mmol/liter (P < 0.001). Metabolic acidosis significantly decreased serum IGF-1 concentration from 45 +/- 6 to 33 +/- 6 nmol/liter (P = 0.002), while serum IGF binding protein 3 concentration was not affected significantly. The growth hormone response to growth hormone releasing factor administration (1 microgram per kg body wt, intravenous bolus) was enhanced significantly during acidosis. The IGF-1 response to growth hormone administration (0.1 U kg body wt subcutaneously, every 12 hr for 48 hr) was blunted significantly during acidosis. Apparent endogenous serum half-life and metabolic clearance rates of growth hormone were not altered significantly by acidosis. Metabolic acidosis in humans results in a significant decrease in serum IGF-1 concentration without a demonstrable effect on IGF binding protein 3, and is related to a resistance to the hepatocellular action of growth hormone. The primary defect in the growth hormone/IGF-1 axis occurs via an impaired IGF-1 response to circulating growth hormone with consequent diminution of normal negative feedback inhibition of IGF-1 on growth hormone, as evidenced by the exaggerated growth hormone response to growth hormone releasing factor administration.

Acidosis↗
PubMed1997

Plasma hypercoagulability in haemodialysis patients: impact of dialysis and anticoagulation.

BACKGROUND: Thrombotic complications are common in patients with endstage renal disease and contribute substantially to the morbidity and mortality in this population. The aim of the present study was to: i) determine the prevalence and the extent of hypercoagulability in patients undergoing dialysis treatment by measuring parameters that directly reflect thrombin concentrations; ii) assess changes in coagulation status during haemodialysis (HD); iii) quantify the relative impact of heparin, dialysis and their combined effects on coagulation status and iv) detect factors that modify coagulation haemostasis in dialysis patients. METHODS: A total of 39 patients (HD: n = 29, CAPD: n = 10) was analysed for procoagulatory and fibrinolytic activity determined by measurements of partial thromboplastin time, prothrombin fragments F1 + 2, thrombin-antithrombin complexes and D-dimer concentrations. HD patients were investigated prior to and during dialysis. A subgroup of patients was infused heparin alone without dialysis or was dialysed without heparin administration. Furthermore, subgroup and correlation analyses were performed for the type of dialysis (HD vs CAPD), dialyzer and shunt, Kt/V, underlying disease and treatment with recombinant erythropoietin (rhEPO). RESULTS: Baseline levels of all parameters-procoagulatory and fibrinolytic--were substantially elevated in all patients, but to a higher degree among those on CAPD. Moreover, haemodialysis treatment increased procoagulatory markers even further, suggesting stimulated coagulation and/or insufficient anticoagulation during dialysis. However, after 3 h of dialysis thrombin concentrations, determined by quantification of prothrombin fragments, were inversely correlated with Kt/V. Selective heparin infusion diminished procoagulatory activity only slightly and incompletely, whereas HD without heparin resulted in excess thrombin accumulation. Finally, subgroup analyses revealed more pronounced thrombin formation among patients treated with polysulfon dialyzers, whereas erythropoietin dosage was positively related with lower procoagulatory activity. CONCLUSION: A majority of patients on dialysis are in a hypercoagulable state, which is further aggravated by the haemodialysis procedure itself and may not be sufficiently controlled with current anticoagulation regimens. Intensified heparin treatment and the use of rhEPO are likely to improve coagulation haemostasis, whereas the type of dialyzer should be considered as a relevant procoagulatory factor.

Adult↗
PubMed1997

Effect of chronic metabolic acidosis on thyroid hormone homeostasis in humans.

The effects of metabolic acidosis on thyroid function are unknown. We investigated the effects of chronic extrarenal acidosis on the hypothalamic-pituitary-thyroid axis. Chronic metabolic acidosis was induced by administering NH4Cl (4.2 mmol.kg body wt-1.day-1) to six normal male volunteers during metabolic balance conditions. Plasma bicarbonate concentration decreased from 25.0 +/- 0.4 to 15.5 +/- 0.9 mmol/l (P < 0.001). Metabolic acidosis significantly decreased serum-free 3,5,3'-triiodothyronine (T3) concentrations from 373 +/- 18 (control) to 251 +/- 13 pg/dl (P < 0.001) and decreased serum-free L-thyroxine (T4) from 1.55 +/- 0.42 to 1.25 +/- 0.37 ng/dl (P < 0.002), whereas serum total reverse T3 did not change significantly. Consequently, the reverse T3-to-free T4 ratio increased. Serum thyroid-stimulating hormone (TSH) levels increased significantly from 0.70 +/- 0.07 during control to 1.30 +/- 0.12 mU/l during acidosis (P < 0.003). The TSH response to thyrotropin (TRH, 2 mg intranasally) was exaggerated in acidosis: the partial area under the concentration curve for the TSH response (210 min post-TRH) was 902 +/- 167 during control compared with 1.394 +/- 209 mU.min.l-1 during acidosis (P = 0.0139). Chronic metabolic acidosis, as produced by the model employed here, induces a decrease in thyroid hormone secretion and might exert additional effects on thyroid hormone metabolism in humans. The acidosis-induced decrease in thyroid function might modulate some of the reported effects of metabolic acidosis, such as on nitrogen balance, protein synthesis, lean body mass, insulin-like growth factor I levels, renal acidification, and cardiac contractile function.

Acidosis↗
PubMed1997

Acid-induced stimulation of Na-Pi cotransport in OK cells: molecular characterization and effect of dexamethasone.

Alterations in systemic acid/base balance affect renal Pi excretion. In the present study, the effects of an acidic pH on apical Na-dependent Pi (Na-Pi) cotransport were analyzed using OK cells (opossum kidney cell line). Cells were maintained at either pH 7.4 or 7.1 (altered HCO3- concentration at constant PCO2). Incubation in acidic medium led to an increase in Na-Pi cotransport activity, which was characterized by a transient, initial response (2-4 h, 25% increase) followed by a sustained response (24 h, 75% increase). Increased Na-Pi cotransport activity (24 h) was sensitive to inhibition by parathyroid hormone. Actinomycin D did not abolish the acid-induced increases (initial and sustained responses). Cycloheximide abolished the increase in Na-Pi cotransport observed after 24 h. The increase in Na-Pi cotransport (24 h) was prevented by dexamethasone (2 x 10(-6) M). Western blots showed a twofold (3 h) and two- to threefold (24 h) increase in NaPi-4 protein after acid exposure. Cycloheximide prevented the late increase in NaPi-4 protein abundance. Also dexamethasone reduced the increase in specific protein content. In conclusion, the exposure of OK cells to an acidic medium causes a stimulation of the NaPi-4 cotransporter that is prevented by dexamethasone.

Animals↗
PubMed1996

[Osteoporosis of the lumbar spine].

This brief review demonstrates a positive influence of the treatment modalities established today on postmenopausal, age-related or glucocorticoid-induced bone loss. Measures developing direct anabolic effects are, however, rare. In other words prevention of osteoporosis is more important than therapy. Prevention means above all to change life style, to prevent excessive post-menopausal mineral losses and to treat patients with long-term steroid regimens in higher doses (over 7.5 mg/day). Preventive measures include adequate intake of calcium, reduced intake of salt, encouraging physical activities as well as avoiding excessive alcohol- and nicotine-consumption. From the osteoporotic point of view estrogen substitution is indicated in post-menopausal women. However, an individual evaluation of the indication is mandatory in view of the above discussed aspects. A densitometry-guided follow-up may contribute by valuable data to this decision. Only if these measures fail may further therapeutic and secondary-preventive measures be taken into consideration. Such secondary-preventive measures comprise anti-resorption drugs (calcitonin, higher doses of vitamin D, bisphosphonates) as well as fluoride which stimulates bone remodeling.

Adult↗
PubMed1996

Glomerulopathy associated with predominant fibronectin deposits: exclusion of the genes for fibronectin, villin and desmin as causative genes.

Glomerulopathy with predominant fibronectin deposits (GFD) is a newly recognized autosomal dominant renal disease that leads to albuminuria, microscopic hematuria, hypertension, renal tubular acidosis type IV, and end-stage renal disease in the second to fourth decade of life. Light microscopy documents extensive deposits in the subendothelial space, which on electron microscopy consist of non-oriented 12 x 125 nm fibers. Deposits are strongly immunoreactive for antibodies to fibronectin. We examined the hypothesis that a genetic defect in the gene for fibronectin is responsible for the disease. In a 197 member pedigree, 13 relatives developed end-stage renal failure from the disease. In 99 individuals haplotype analysis was performed using 6 microsatellite markers spanning a > 56 cM interval in chromosome region 2q34, where fibronectin, villin, and desmin map in close proximity. Haplotype analysis resulted in exclusion of the whole range of 78 cM covered by the markers examined. This result excludes fibronectin, villin, and desmin from being the causative genes for GFD in this large kindred.

Calcium-Binding Proteins↗
PubMed1996

Effect of postoperative intravenous loop diuretic on renal function after major surgery.

OBJECTIVE: To determine the effect on renal function of postoperative continuous, intravenous furosemide after major thoraco-abdominal or vascular surgery. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Intensive care unit of a referral hospital in Eastern Switzerland. METHODS: Furosemide (1 mg/h) or placebo was administered to 121 consecutive patients admitted to the intensive care unit after major abdominal, chest or vascular surgery and continued throughout the intensive care treatment period. Enrollment was performed during a 6 months period. No patient was excluded. Renal function was determined serially by measuring creatinine clearances and plasma creatinine concentrations. RESULTS: Postoperatively, creatinine clearance decreased significantly to 83% (furosemide) and to 81% (placebo group) of the initial value (p = 0.004). This decrease was not affected significantly by furosemide. Retrospective subgroup analysis using stepwise regression also did not show any differences between the groups. Hypokalemia was detected in 36 (furosemide) versus 19% of the blood sample (placebo, p = 0.006). CONCLUSIONS: Low-dose intravenous furosemide appears to offer no advantage over placebo in an unselected group of patients with moderate postoperative renal impairment. As no patients with acute renal failure necessitating dialysis were observed during the study period, the effect of furosemide in more severe postoperative renal impairment and the effects of higher doses of loop diuretics remain to be investigated.

Aged↗
PubMed1996

[Iatrogenic hyperkalemia].

Iatrogenic causes are important contributors to hyperkalemia in clinical practice. Most iatrogenic causes are drug-related, involving interference by the drugs with potassium metabolism at the level of renal handling and/or transcellular distribution of potassium. By discussion of the mechanisms of iatrogenic hyperkalemia it is hoped that the incidence of this potentially serious complication can be reduced.

Aldosterone↗
PubMed1996

Familial glomerulopathy with giant fibrillar (fibronectin-positive) deposits: 15-year follow-up in a large kindred.

A 15-year clinical follow-up is reported for a familial glomerulopathy characterized on light microscopy by the glomerular deposition of giant fibrillary deposits (Virchows Arch A Pathol Anat Histol 388:313-326, 1980). On electron microscopy, the deposits consist of randomly oriented fibrils (12 to 16 nm in width and 120 to 170 nm in length). These deposits show positive immunoreactivity for fibronectin. One hundred fifty-seven of 197 family members within five generations were investigated. The disease is characterized by the occurrence of albuminuria in the third to fourth decades of life and slow progression to end-stage renal disease over a period of 15 to 20 years with the occurrence of generalized distal tubular acidosis (renal tubular acidosis type IV), hypertension, and the nephrotic syndrome. The frequent occurrence of otherwise unexplained microalbuminuria in young individuals of generations IV and V could be indicative of incipient glomerular disease. In one affected male individual and in his unaffected sister, renal cell carcinoma was diagnosed, raising the possibility that this familial glomerulopathy might be associated with an increased risk to develop renal cell cancer by direct or indirect (associated genetic predisposition) mechanisms. The disease relapsed in one renal transplant, raising the possibility of the presence of a transferable factor that could be part of the deposited fibrillar material or, alternatively, interfere with the glomerular handling of the deposited material.

Acidosis, Renal Tubular↗
PubMed1995

Plasma potassium response to acute respiratory alkalosis.

Acute respiratory alkalosis (hyperventilation) occurs in clinical settings associated with electrolyte-induced complications such as cardiac arrhythmias (such as myocardial infarction, sepsis, hypoxemia, cocaine abuse). To evaluate the direction, magnitude and mechanisms of plasma potassium changes, acute respiratory alkalosis was induced by voluntary hyperventilation for 20 (18 and 36 liter/min) and 35 minutes (18 liter/min). The plasma potassium response to acute respiratory alkalosis was compared to time control, isocapnic and isobicarbonatemic (hypocapnic) hyperventilation as well as beta- and alpha-adrenergic receptor blockade by timolol and phentolamine. Hypocapnic hypobicarbonatemic hyperventilation (standard acute respiratory alkalosis) at 18 or 36 liter/min (delta PCO2-16 and -22.5 mm Hg, respectively) resulted in significant increases in plasma potassium (ca + 0.3 mmol/liter) and catecholamine concentrations. During recovery (post-hyperventilation), a ventilation-rate-dependent hypokalemic overshoot was observed. Alpha-adrenoreceptor blockade obliterated, and beta-adrenoreceptor blockade enhanced the hyperkalemic response. The hyperkalemic response was prevented under isocapnic and isobicarbonatemic hypocapnic hyperventilation. During these conditions, plasma catecholamine concentrations did not change. In conclusion, acute respiratory alkalosis results in a clinically significant increase in plasma potassium. The hyperkalemic response is mediated by enhanced alpha-adrenergic activity and counterregulated partly by beta-adrenergic stimulation. The increased catecholamine concentrations are accounted for by the decrease in plasma bicarbonate.

Acute Disease↗
PubMed1995

Glomerulopathy associated with predominant fibronectin deposits: a newly recognized hereditary disease.

A newly recognized type of familial glomerulopathy observed in patients of both sexes in six families is reported. Proteinuria, often within the nephrotic range, microscopic hematuria, hypertension and a slowly decreasing renal function over several years were common. No underlying systemic diseases were identified. Generally, light microscopy showed enlarged glomeruli with minimal hypercellularity and with extensive deposits in the mesangium and subendothelial space. By electron microscopy, granular deposits with some admixture of fibrils were most common. In one family, the deposits were predominantly fibrillary. Immunoglobulins and complement factors were inconstant or lacking. A main finding was a strong immune reactivity to fibronectin, corresponding to the distribution of the deposits. In one patient, the deposits recurred in a renal transplant. There was no indication of systemic deposition. Abnormalities in the metabolism of circulating fibronectin may play a pathogenetic role in this disease of probably autosomal dominant inheritance.

Adolescent↗
PubMed1995

Neutral phosphate administration generates and maintains renal metabolic alkalosis and hyperparathyroidism.

We examined the effects of chronic intravenous neutral phosphate administration on systemic acid-base equilibrium and parathyroid function in six normal, NaCl-replete male human subjects under metabolic balance conditions. The subjects received 4.35 mmol of neutral sodium phosphate.kg body wt-1.day-1 intravenously and continuously for 7 days and the same amount of sodium as NaCl during control and recovery. Blood pH increased from 7.388 to 7.411 (P < 0.001) and plasma bicarbonate from 23.5 to 26.0 mmol/l (P < 0.001). Urinary pH increased from 6.58 to 6.79 (P < 0.001). Net acid excretion increased from 59 to 100 mmol/24 h (P < 0.001). Plasma ionized calcium concentration decreased and plasma phosphate concentration increased transiently. Serum intact parathyroid hormone increased from 24 to 62 pg/ml (P < 0.001). Chronic phosphate administration also resulted in a significant increase in renal phosphate clearance (35 to 229 ml/min) and decrease in the fractional excretion of calcium (1.8 to 0.9%). Thus chronic intravenous phosphate administration generates and maintains renal metabolic alkalosis in salt-replete humans and induces hyperparathyroidism. The severity of metabolic alkalosis is mitigated by an apparent increase in effective endogenous acid production as evidenced by the significant increase in steady-state net acid excretion.

Acid-Base Equilibrium↗
PubMed1995

Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans.

Chronic metabolic acidosis has been previously shown to stimulate protein degradation. To evaluate the effects of chronic metabolic acidosis on nitrogen balance and protein synthesis we measured albumin synthesis rates and urinary nitrogen excretion in eight male subjects on a constant metabolic diet before and during two different degrees of chronic metabolic acidosis (NH4Cl 2.1 mmol/kg body weight, low dose group, and 4.2 mmol/kg body weight, high dose group, orally for 7 d). Albumin synthesis rates were measured by intravenous injection of [2H5ring]phenylalanine (43 mg/kg body weight, 7.5 atom percent and 15 atom percent, respectively) after an overnight fast. In the low dose group, fractional synthesis rates of albumin decreased from 9.9 +/- 1.0% per day in the control period to 8.4 +/- 0.7 (n.s.) in the acidosis period, and from 8.3 +/- 1.3% per day to 6.3 +/- 1.1 (P < 0.001) in the high dose group. Urinary nitrogen excretion increased significantly in the acidosis period (sigma delta 634 mmol in the low dose group, 2,554 mmol in the high dose group). Plasma concentrations of insulin-like growth factor-I, free thyroxine and tri-iodothyronine were significantly lower during acidosis. In conclusion, chronic metabolic acidosis causes negative nitrogen balance and decreases albumin synthesis in humans. The effect on albumin synthesis may be mediated, at least in part, by a suppression of insulin-like growth factor-I, free thyroxine and tri-iodothyronine.

Acidosis↗
PubMed1994

Induction of the putative copper ATPases, CopA and CopB, of Enterococcus hirae by Ag+ and Cu2+, and Ag+ extrusion by CopB.

The two P-type ATPases CopA and CopB are effecting regulation of cellular copper activity in Enterococcus hirae. With antibodies against these ATPases, we showed on Western blots the simultaneous induction of CopA and CopB by copper or silver ions. Copper contents of wild type and mutant cells lacking either CopA, CopB or both enzymes were measured by atomic absorption. Strains disrupted in copB showed clearly enhanced copper contents. Mutants lacking CopB also lost the ability of energy dependent efflux of silver ions. Our results demonstrate that CopA and CopB are under the same genetic control and support the proposal that CopB is a copper and silver exporting ATPase.

Adenosine Triphosphatases↗
PubMed1994

Copper pumping ATPases: common concepts in bacteria and man.

Recently, four genes encoding putative copper pumping ATPases have been cloned from widely different sources: two genes from Enterococcus hirae that are involved in copper metabolism and two human genes that are defective in the copper-related Wilson and Menkes disease. The predicted gene products are P-type ATPases. They exhibit extensive sequence similarity and appear to be members of a new class of ATP driven copper pumps involved in the regulation of cellular copper.

Adenosine Triphosphatases↗
PubMed1994

Functional adaptation to high PCO2 of apically and basolaterally located Na+/H+ exchange activities in cultured renal cell lines.

Cultured renal epithelial cells grown on filter support were examined for functional adaptation of Na+/H+ exchange activities to "respiratory" acidaemia, which was mimicked by increasing PCO2 from 5% to 10% during 24 h or 48 h of cell culture. We have selected proximal tubular cell lines with either dual location of Na+/H+ exchange activities (MCT cells, RKPC-2 cells), apical location of Na+/H+ exchange activity (OK/WOK cells) or a basolateral location of Na+/H+ exchange activities (LLC-PK1/clone 4 cells, MDCK cells). Na+/H+ exchange activity was determined microspectrofluorometrically (using BCECF) in the absence of CO2/HCO3-. Respiratory acidaemia specifically increased apical Na+/H+ exchange activity (previously classified as amiloride-resistant) in MCT cells, in RKPC-2 cells and in WOK cells; it stimulated basolateral Na+/H+ exchange activity (previously shown to be amiloride-sensitive) in RKPC-2 cells, in LLC-PK1/clone 4 cells and in MDCK cells, but did not affect basolateral Na+/H+ exchange activity in MCT cells. In MCT and in RKPC-2 cells the effect of high PCO2 on apical Na+/H+ exchange was prevented by inhibition of protein kinase C. In RKPC-2 cells, activation of basolateral Na+/H+ exchange by high PCO2 occurred also when protein kinase C was inhibited. In conclusion, these studies demonstrate stimulation of apical Na+/H+ exchange, but differential regulation of basolateral Na+/H+ exchange activities in response to a high-PCO2-induced acid environment. Protein kinase C activation might be involved in mediating the effect of acidaemia on stimulation of apical Na+/H+ exchange activity (MCT and RKPC-2 cells).

Adaptation, Physiological↗