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Biomedical subjects

F F Horber

Publications and source records attributed to F F Horber.

At least 37 records · Page 2Linked to original sources

Altered parathyroid gland function in severely immunocompromised patients infected with human immunodeficiency virus.

Several endocrine functions have been found disturbed in patients with acquired immunodeficiency syndrome (AIDS). However, no information is available on parathyroid function in these patients. Six patients with AIDS and 10 healthy volunteers underwent an EDTA infusion to induce hypocalcemia and stimulate PTH secretion. A group of 6 severely ill patients with malignancies was studied at baseline and served as additional controls for the effect of a severe disease per se. Baseline values showed that mean serum intact PTH concentration was lower in patients infected with the human immunodeficiency virus than in healthy volunteers (P < 0.04) as well as in patients with malignancies (P = 0.004). Whole blood calcium also tended to be lower in patients with the human immunodeficiency virus than in both control groups, the difference reaching the limit of statistical significance for the healthy controls only (P < 0.04). Mean serum magnesium, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations were similar in both groups. Throughout the entire EDTA stimulation procedure, i.e. at any blood calcium concentration, serum intact PTH concentration remained lower in patients with AIDS than in healthy control subjects (P < 0.04, analysis of variance for repeated measurements). Basal and maximal secretion of PTH is reduced in patients with AIDS. The mechanisms underlying this finding remain speculative.

Acquired Immunodeficiency Syndrome↗

[The accuracy of intravenous digital subtraction angiography regarding kidney arteries in hypertensive patients. A contribution to cost control in diagnostic medicine].

In a retrospective study the results of intravenous digital subtraction angiography (DSA) of renal arteries from 149 hypertensive outpatients investigated 1984 to 1989 at the University of Berne were evaluated. 118 i.v. DSA's (79%) were normal, 10 (7%) were inconclusive and 21 (14%) revealed stenosis. In 16 patients the course of the vessel and the degree of stenosis were verified by intraarterial DSA. In nine patients (6%) a significant stenosis was confirmed and subsequently treated by percutaneous transluminal angioplasty. Renal size was not a predictive parameter for stenosis in this population. Accessory renal arteries were found in 44% of patients with stenosis and only in 18% of those without. The late phase images of i.v. DSA revealed many morphologic abnormalities. The indication for i.v. DSA was assessed according to internationally accepted criteria: 1. severe hypertension, 2. hypertension refractory to treatment, 3. hypertension of sudden onset or aggravation, 4. onset of hypertension in patients younger than 20 or older than 50 years. In the group without stenosis (n = 118) 52 patients (44%) did not fulfill a single one of these criteria, whereas the patients with stenosis (n = 9) had at least one criterion fulfilled. Hypertensive patients should, therefore, only be studied by i.v. DSA if at least one criterion applies. 22,000 SFr. could thus have been saved without loss of medical quality and the treatment options.

Angiography, Digital Subtraction↗

Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents.

Lean, healthy normotensive sons of essential hypertensive parents (OHyp) have lower insulin sensitivity (SI) than sons of normotensive parents (ONorm). We have tried to find out whether this disturbance in insulin metabolism is related to altered body fat distribution, fuel metabolism, or both. 21 OHyp and 21 ONorm of similar age and body-mass index were investigated after fasting overnight. Body composition was assessed by dual-energy X-ray absorptiometry and fuel metabolism by indirect calorimetry and urinary nitrogen excretion. Plasma insulin and glucose concentrations were measured during the frequent sampling intravenous glucose tolerance test, and SI was calculated by the minimum model method. Systolic blood pressure and heart rate were slightly but not significantly higher in OHyp than ONorm but the groups did not differ in fasting plasma insulin or glucose concentrations, carbohydrate or lipid oxidation, lean and fat mass, bone mineral content, or distribution of body fat. By contrast, SI was significantly lower in OHyp than ONorm (8.2 [0.7] vs 13.4 [1.5] 10(-4) L mU-1 min-1, p < 0.01). Within the whole study population upper-body fat mass was positively correlated with fasting plasma insulin (r = 0.33, p < 0.03) and lipid oxidation was positively correlated with SI (r = 0.35, p < 0.04) and negatively correlated with subscapular/triceps skinfold thickness (r = -0.43, p < 0.01). Thus, impairment of SI precedes both the development of overt hypertension and gain or redistribution of body fat. Therefore, the concept that SI is low as a result of altered fat distribution has to be reconsidered, at least in young male offspring of hypertensive parents.

Adipose Tissue↗

Visceral leishmaniasis after orthotopic liver transplantation: impact of persistent splenomegaly.

Visceral leishmaniasis was observed in a 50-year-old female liver transplant recipient 1 year following transplantation. Signs of active infection were low-grade fever, pancytopenia, persistent splenomegaly, positive cultures for leishmania in liver and bone marrow biopsy specimens, and newly positive leishmania serology. Following sequential therapy with pentavalent antimony and amphotericin B, blood values improved massively, bone marrow cultures became negative, and leishmania serology decreased. Secondary prophylaxis with fluconazole was instituted and the patient remains without signs of active infection 1 year after successful therapy.

Female↗

Effect of human growth hormone and insulin-like growth factor I on whole-body leucine and estimates of protein metabolism.

Recombinant human growth hormone (rhGH) administration to normal volunteers increases estimates of whole-body and forearm protein synthesis but has little effect on rates of proteolysis in both the postabsorptive state and during meal absorption. In contrast, insulin decreases estimates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimates of protein synthesis. We have used high-dose prednisone as a controlled model for protein catabolism in normal volunteers and demonstrated that glucocorticosteroids increase estimates of whole-body proteolysis and the oxidation of leucine with little or no effect on estimates of whole-body protein synthesis. We have recently demonstrated that high-dose rhGH together with prednisone prevents the protein-catabolic effects observed with treatment with prednisone alone, while inducing insulin resistance and increased secretion of proinsulin. GH is thought to mediate its effects via the generation of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF-I induce hypoglycemia and decrease estimates of whole-body proteolysis and suppress the secretion of GH, insulin and glucagon, suggesting a predominant insulin-like effect on protein and glucose metabolism. When rhIGF-I is infused at a rate that achieves plasma IGF-I concentrations similar to those observed during rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein synthesis were not affected in the absence or presence of prednisone treatment. When rhGH and rhIGF-I are administered simultaneously, nitrogen balance is remarkably improved. Thus, the mechanism of action of both rhGH and/or rhIGF-I on body protein metabolism remains to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth Hormone↗

Effect of glucocorticoid and growth hormone treatment on proinsulin levels in humans.

Treatment with glucocorticoids is associated with a disproportionate elevation in the PI/IRI ratio. To determine whether growth hormone--another agent capable of producing insulin resistance and changing B-cell function--also alters the PI/IRI ratio and whether growth hormone and glucocorticoids have a synergistic effect on PI and IRI levels, we examined these variables in four groups of young healthy subjects (n = 8/group) after 7 days of treatment with placebo, prednisone (0.8 mg.kg-1 x day-1), rhGH (0.1 mg.kg-1 x day-1), and the combination of prednisone and rhGH. Fasting plasma glucose levels increased significantly above those of the control group in subjects receiving prednisone or prednisone and rhGH but not in subjects receiving rhGH alone. The basal concentration of IRI increased in response to prednisone, rhGH, and the combination of prednisone and rhGH. However, this increase in IRI was largely due to an increase in PI, so that the PI/IRI ratio increased from 14.7 +/- 2.4% in control subjects to 33.9 +/- 5.3% in subjects on prednisone (P < 0.005), 40.9 +/- 4.3% in individuals receiving rhGH (P < 0.001 vs. control subjects), and 58.1 +/- 9.2% in subjects receiving both prednisone and rhGH (P < 0.001 vs. control subjects). We suggest that this change in PI/IRI with glucocorticoid and growth hormone treatment may be due to an alteration in B-cell synthesis or release of PI. This change in the PI/IRI ratio is not dependent on fasting hyperglycemia but may contribute to the hyperglycemia often observed with these agents. Furthermore, these data show that IRI is not a reliable indicator of true insulin levels or insulin sensitivity in either growth hormone- or glucocorticoid-treated subjects.

Adult↗

Impact of time-interval after transplantation and therapy with fibrates on serum cholesterol levels in renal transplant patients.

It is unclear to what extent different immunosuppressive regimens contribute to increased serum cholesterol levels observed in renal transplant patients after prolonged periods of immunosuppression (i.e. 3 and 5 years following kidney grafting). Therefore 2 groups of renal transplant patients were evaluated with respect to serum cholesterol 3 years (n = 103) and 5 years (n = 66) after transplantation: Group 1: prednisone (Pred)/azathioprine (Aza) [3 years (y): n = 52; 5 y: n = 49; mean prednisone dose 12 +/- 1 mg/day]; group 2: cyclosporine A (CsA) alone or in combination with Pred (3 y: n = 51; 5 y: n = 17; prednisone dose 4 +/- 2 mg/day, p < 0.001 vs group 1). The groups were similar with respect to age, sex, body mass index, time interval after transplantation, underlying kidney diseases and concomitant drug therapy. Serum cholesterol levels were persistently higher in patients of group 2 when compared to group 1 (3 years: 7.3 +/- 0.2 vs 6.7 +/- 0.2 mmol/l, p < 0.01; 5 years: 7.5 +/- 0.1 vs 6.6 +/- 0.3 mmol/l, p < 0.01) despite 75% lower daily doses of Pred (p < 0.001) in CsA treated patients (group 2). Before transplantation, patients exhibited a similar distribution of serum cholesterol levels when compared to age, sex and body mass index matched healthy subjects. In contrast 3 and 5 years following transplantation 72% of the patients had serum cholesterol levels above 6.5 mmol/l, whereas in normal subjects, 60% had serum cholesterol levels below 6.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Toxicity of an organic Germanium compound: deleterious consequences of a "natural remedy"].

Reports mainly from Japan, recommend germanium (Ge)-containing compounds as "anti-cancer" and "immunostimulatory" remedies. We report on a 25-tear-old woman with stage II HIV disease who consumed a total of 47 g Ge as Ge-lactate-citrate 18%. She developed severe renal insufficiency (creatinine clearance 7 ml/min/1.73 m2, proteinuria 0.28 g/d) and hepatomegaly. Biopsies revealed tubulointerstitial nephropathy with vacuolar degeneration, mainly of distal tubular epithelia, and severe liver steatosis. Tissue Ge content in kidney and liver biopsy specimens was increased 68-and 140 fold respectively. In agreement with previous reports, renal dysfunction persisted 9 months later (creatinine clearance 11 ml/min/1.73 m2).

Acute Kidney Injury↗

Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans.

The present studies were performed to test the hypothesis that the liver, by increasing the synthesis of specific plasma proteins during the absorption of an amino acid meal, may play an important role in the temporary "storage" of ingested essential amino acids and to explore the effects of glucocorticosteroids and recombinant human growth hormone (rhGH) on these processes. The fractional synthetic rates of albumin and fibrinogen were determined using simultaneous infusions of intravenous [1-14C]leucine and intraduodenal [4,5-3H]leucine after 22 h fasting and during absorption of glucose and amino acids in four groups of normal subjects treated for 1 wk with placebo, prednisone (0.8 mg.kg-1.day-1), rhGH (0.1 mg.kg-1.day-1), or combined treatment. When compared with the fasted state and independent of the route of tracer delivery and hormonal treatment, albumin, but not fibrinogen, synthesis increased (P < 0.0001) during absorption of a mixed glucose amino acid meal in all groups. This increase in albumin synthesis accounted for 28% of the increase in whole body protein synthesis associated with feeding and for 24, 22, and 14% in the prednisone, rhGH, and combined treatment groups, respectively. These data suggest that the stimulation of albumin synthesis observed during feeding prevents irreversible oxidative losses of a significant fraction of ingested essential amino acids and may serve as a vehicle to capture excess dietary amino acids and transport them to peripheral tissues to sustain local protein synthesis.

Adult↗

Human growth hormone but not insulin-like growth factor I positively affects whole-body estimates of protein metabolism.

Human growth hormone (rhGH) increases estimates of whole-body protein synthesis, but has little effect on rates of proteolysis in both the postabsorptive state and during meal absorption. In addition, rhGH stimulates protein synthesis in skeletal muscle tissue. In contrast, insulin decreases estimates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimates of protein synthesis. Using high-dose prednisone as a controlled model for protein catabolism in normal volunteers, high-dose rhGH together with prednisone prevents the protein catabolic effects of prednisone alone. GH is thought to mediate its effects via the generation of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF-I induce hypoglycemia and decrease estimates of whole body proteolysis, suggestive of a predominant insulin-like effect. When rhIGF-I is infused at a rate that achieves plasma IGF-I concentrations similar to those observed during rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein synthesis were not affected in the absence or presence of prednisone treatment. Thus, the mechanism of action of rhGH on body protein metabolism remains to be elucidated. However, rhGH alone or in combination with rhIGF-I may provide a new management strategy in a variety of protein catabolic conditions in humans.

Adrenal Cortex Hormones↗

The effects of human growth hormone and prednisone on whole body estimates of protein metabolism.

Human growth hormone (GH) increases estimates of whole body protein synthesis, but has little effect on the rates of proteolysis either post-absorptively or when absorption occurs during a meal. In contrast to insulin, GH stimulates protein synthesis in skeletal muscle tissue. Prednisone in high doses induces protein catabolism and has been used as a controlled model for catabolic illness. Prednisone increases the rates of proteolysis and amino acid oxidation, but has little effect on estimates of protein synthesis. The administration of high doses of GH together with prednisone prevents the protein catabolic effects of prednisone alone. Thus, GH may provide a new management strategy in patients with significant protein catabolic conditions.

Growth Hormone↗

Low dose recombinant human insulin-like growth factor-I fails to affect protein anabolism but inhibits islet cell secretion in humans.

The in vivo effects of recombinant human insulin-like growth factor-I (rhIGF-I) on whole body protein metabolism were studied to ascertain whether rhIGF-I has comparable effects as those reported with rhGH use in humans. The doses of rhIGF-I chosen achieved similar plasma IGF-I concentrations as those achieved after 7 days of rhGH injections. Eight normal volunteers were studied using [1-13C]- and [1-14C]leucine tracers, before, 4 h, and 28 h after a continuous infusion of rhIGF-I at 5 micrograms kg-1 h-1 (n = 6) and 10 micrograms kg-1 h-1 (n = 2). Two additional subjects were studied in a protein catabolic state after 7 days of high dose (0.8 mg kg-1 day-1) glucocorticosteroid administration. Plasma concentrations of rhIGF-I were similar using either 5 or 10 micrograms kg-1 h-1 and increased to values approximately 300% above baseline by 28 h of infusion. No decrease in the plasma glucose concentration was observed during the 28-h infusion; however, plasma insulin, C-peptide, and glucagon concentrations significantly decreased, whereas plasma free fatty acids were not affected. No changes were observed in the rate of proteolysis (as estimated by the rate of leucine appearance), the rate of leucine oxidation, or the rate of protein synthesis in the absence or presence of glucocorticosteroid treatment. Plasma concentrations of insulin-like growth factor binding protein-3 did not change during the rhIGF-I infusion whereas they increased 50% in subjects who received rhGH, and in whom rhGH caused a potent protein anabolic effect. These results suggest that rhIGF-I may have a somatostatin-like effect. In addition, we found that rhIGF-I infusion is insufficient to promote protein anabolism. This may be due to the failure of rhIGF-I alone to induce a pivotal GH-dependent cofactor(s) necessary for IGF-I to elicit an anabolic effect on protein metabolism in humans.

Adult↗

Impact of hydration status on body composition as measured by dual energy X-ray absorptiometry in normal volunteers and patients on haemodialysis.

To evaluate the influence of hydration status on the estimation of body composition using dual-energy X-ray absorptiometry (DXA), six normal volunteers and seven patients on maintenance haemodialysis were investigated using two different DXA machines (Lunar DPX, Hologic QDR 1000/W). Normal volunteers were studied (Hologic QDR 1000/W) before and 1 h after ingestion of breakfast, lunch and dinner (drinking various amounts of liquids at each meal, 0.5-2.4 kg). Whereas bone mineral content and body fat mass did not change, lean body mass of the trunk increased as a consequence of the meals. Conversely in patients on haemodialysis (Lunar DPX), lean body mass decreased in all segments of the body as a consequence of removal of 0.9-4.4 kg of salt-containing fluid by haemodialysis (trunk 61%, legs 30%, arms 5.5% and rest of the body 3.5%), whereas bone mineral content and body fat mass remained unchanged. However, this finding(s) did not hold true in one particular patient with bilateral hip prostheses. Measurement of body composition in eight normal volunteers on the same day with both machines showed similar results for lean and fat mass, whereas bone mineral content was found to be 17% higher using the Lunar DPX. In summary, in centres where both machines are available, follow-up of one individual patient should always be performed using the same equipment. In addition, hydration status and food intake must be taken into account when repetitive measurements of lean body mass are performed in the same patient.

Absorptiometry, Photon↗

Impact of dialysis modality on body composition in patients with end-stage renal disease.

Loss of muscle mass and altered body fat distribution (i.e. increased central fat stores in the presence of normal peripheral fat stores) have been reported in patients on hemodialysis (HD), when compared to normal volunteers. Whether treatment of end-stage renal disease (ESRD) with continuous ambulatory peritoneal dialysis (CAPD) would alter body composition in a different manner than HD is unknown. To answer this question, two groups (n = 11 each) of male patients with ESRD (matched for age, residual renal function, body weight and body height as well as physical activity) were studied. Muscle mass and body fat distribution were assessed using computed tomography. Mid-thigh muscle area, peripheral and central fat stores were similar between the two groups of dialysis patients. In both patient groups muscle mass and fat stores were independent of duration of dialysis, age, daily protein intake and residual renal function. In CAPD-patients mid-thigh muscle area was correlated with plasma albumin (r = 0.56, p < 0.05), while serum cholesterol level was correlated with mediastinal fat area (r = 0.81, p < 0.01). The present results indicate that both treatment modalities of ESRD (HD vs CAPD) result in similar changes of body composition. Despite continuous glucose loading in CAPD-patients, neither central nor peripheral fat stores are increased in these subjects compared with HD treated patients.

Adipose Tissue↗

Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans.

Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation [( 14C]leucine) increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗