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Biomedical subjects

U Keller

Publications and source records attributed to U Keller.

At least 289 records · Page 16Linked to original sources

[Technology of sewage sludge hygienization].

That the use of modern technology against the laws of Nature must fail, has been clearly demonstrated again some years ago when sewage sludge postpasteurization was rashly introduced. Although many attempts were made to improve this procedure, it had to be abandoned because of unavoidable massive regrowth of pathogens which invaded the germ-free postpasteurized sludge. In contrast of postpasteurization, long-term large-scale tests with the pasteurization of fresh sludge (prepasteurization) have demonstrated that this procedure where methane digestion with its pathogen displacing effect constitutes the final stage, is basically able to function. With respect to the Swiss Sewage Sludge Decree which came into force in May 1981, and which imposes sludge hygienization for most applications throughout the year, various thermal prepasteurization methods have been offered on the market ready for application to meet the legally prescribed requirements. However, some of them still need selective improvements in order to ensure the desired hygienisation effect permanently. For some time now, attention has been focussed on a novel biological 2-stage procedure based on partial aerobic thermophilic fermentation followed by anaerobic sludge digestion which in addition to good hygienisation promises improved sludge thickening, reduced digestion time, more favourable energy consumption and added process stability etc. Although it has already been offered on the market, this interesting process is being thouroughly tested and optimized in parallel pilot tests plant at the WWTP Altenrhein. Finally, reference is made to further sludge treatment processes such as sludge drying and sludge composting which mostly comprise efficent sludge hygienisation although they may not entirely prevent pathogenic regrowth. Moreover, some unconventional and less popular processes such as liquid sludge irradiation and chemical methods are also mentioned.

Electrons↗

[DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, deafness) with cerebello-pontine atrophy].

The case is reported of a 32-year old women of Dutch origin who presented with diabetes insipidus, diabetes mellitus, atrophy of the optic nerve, and dilatation of the urinary tract, the combination known as "DIDMOAD syndrome". Unusual features of this case were regional atrophy of the cerebellum and the pons, and hydrocephalus internus which were associated with alterations of personality and mental function. The clinical symptoms of the syndrome simulated "essential" type 1 diabetes with advanced complications such as retinopathy and autonomous and peripheral neuropathy. The presence of diabetes insipidus with polyuria and polydipsia was not recognized for years because the symptoms were ascribed to diabetes mellitus. The neurologic and psychological symptoms in this patient suggest a more generalized defect of the central nervous system in this syndrome than has been observed previously. Recognition of the condition is of importance because it requires specific therapeutic measures (e.g. for diabetes insipidus), and because of the genetic and prognostic implications.

Adult↗

[Glucagonoma syndrome in a multihormonal pancreatic tumor].

A 60-year-old patient developed signs and symptoms of glucagonoma syndrome (dermatitis, weight loss, anemia and hypoaminoacidemia). However, diabetes mellitus was absent. Glucagonoma was suspected because of markedly elevated plasma glucagon levels and the tumor was subsequently removed by surgery. Acidethanol extraction of the tumor and immunohistochemistry provided evidence of the presence of all four islet hormones, particularly that of glucagon and pancreatic polypeptide and to a lesser extent of somatostatin and insulin. Immunohistochemistry of the tumor (but not plasma) also showed the presence of alpha-HCG. Plasma glucagon immunoreactivity consisted to a large extent (approx. 90%) of a high molecular form of glucagon, probably proglucagon. In spite of the presence of alpha-HCG - which is assumed to be a marker of malignancy - the patient has been free of recurrence for the 2 1/2 years since surgery. The increasing number of cases reported during the past few years demonstrates that the syndrome is more common than previously suspected. Glucagon secretion and its typical clinical picture may be a valuable marker of a multihormonal pancreatic tumor. In a case of suspected glucagonoma, diagnosis can be established simply by obtaining a plasma glucagon level measurement.

Adenoma, Islet Cell↗

Enniatin synthetase, a novel type of multifunctional enzyme catalyzing depsipeptide synthesis in Fusarium oxysporum.

Enniatin synthetase, a multifunctional enzyme catalyzing depsipeptide formation in Fusarium oxysporum was purified to 98% homogeneity as judged by analytical disc gel electrophoresis. The enzyme consists of a single polypeptide chain of a molecular weight of about 250 000. Similar to a number of peptide synthetases and to fatty acid synthetase the enzyme contains 4'-phosphopantetheine as a prosthetic group. Studies on substrate specificity revealed that the enzyme is capable of synthesizing enniatins A--C and also mixed-type enniatins containing more than one species of amino acid. A linear dependence of rate of enniatin synthesis on enzyme concentration was observed, indicating that depsipeptide formation is an intramolecular process. Omission of the methyl donor S-adenosyl-L-methionine resulted in the formation of unmethylated enniatins with a reaction rate of about 10% of that observed in the case of enniatins. Sulfhydryl-directed reagents generally had an inhibitory influence on enniatin synthesis. However, inhibition studies with iodoacetamide revealed that it behaves differently toward the hydroxy acid site(s) and amino acid site(s). This indicates the presence of chemically distinct thiol groups in the active sites for the two substrates.

Amino Acids↗

Failure of glucagon to stimulate ketone body production during acute insulin deficiency or insulin replacement in man.

To assess the role of glucagon and insulin in the acute regulation of ketone body kinetics in man, somatostatin was administered with various combinations of these hormones by replacement infusions in groups of six to seven normal subjects. Somatostatin-induced insulin and glucagon deficiency produced a threefold increase in total ketone body concentrations within 2 h. This increase was the combined result of enhanced production (71%), and decreased metabolic clearance (32%), as determined by 14C-acetoacetate infusions. An associated elevation of non-esterified fatty acids (66%) and glycerol levels occurred. Glucagon replacement (2 ng . kg-1 . min-1) during insulin deficiency failed to enhance ketogenesis or lipolysis but lowered the beta-hydroxybutyrate/acetoacetate concentration ratios. Hyperglycaemia, observed during glucagon administration and insulin deficiency, did not diminish ketone body production or lipolysis. In contrast, insulin replacement (150 microunits . kg-1 . min-1) diminished lipolysis, lowered ketone production, and elevated the metabolic clearance rate of ketone bodies. Glucagon infusions (2 and 4 ng . kg-1 . min-1) during somatostatin and insulin replacement did not accelerate ketone body production or raise non-esterified fatty acid levels, but produced a dose-dependent elevation of blood glucose levels. The results suggest that glucagon is not an important ketogenic hormone under the conditions studied.

Adult↗

Comparative effects of synthetic and natural secretin on pancreatic secretion and on secretin, insulin, and glucagon levels in man.

The effect of synthetic secretin (Roche) on exocrine pancreatic secretion and on secretin, insulin, and glucagon levels was determined and compared with that of pure natural porcine secretin (GIH, Karolinska Institutet, Stockholm) in 10 healthy volunteers. The two secretin preparations were found to be equipotent. Equipotency applies to pancreatic secretion and to secretin and insulin plasma levels, whereas the plasma levels of glucagon were not affected by either drug. It is concluded that this synthetic secretin preparation is suitable for clinical and research purposes.

Adult↗

Effect of somatostatin and two of its analogues on basal and arginine-stimulated insulin and glucagon secretion in the dog.

Two analogues of somatostatin (D-Trp8,D-Cys14-somatostatin, and the octapeptide DesAA1,2,3,4,13,14,D-Trp8,GABA12-somatostatin) were compared with somatostatin using infusions of 0.1 and 0.5 microgram . kg-1 . min-1 in conscious dogs. Basal concentrations of insulin and glucagon were markedly and similarly lowered by all three somatostatin (SRIF) compounds at either dose. Arginine stimulation of insulin and glucagon secretion was entirely abolished by SRIF and by the octapeptide during infusion at 0.1 microgram . kg-1 . min-1 but both hormones were only partly inhibited by D-Trp8,D-Cys14-SRIF. The higher dose (0.5 microgram . kg-1 . min-1) of all three SRIF peptides lowered plasma insulin and glucagon before and during arginine stimulation. The recovery of plasma insulin and glucagon was delayed after discontinuation of the D-Trp8,D-Cys14-SRIF, and particularly after the octapeptide when compared with SRIF suggesting a longer duration of action of the analogues. The results did not confirm the previously suggested selective suppression of glucagon by D-Trp8,D-Cys14-SRIF. The new octapeptide appears to be promising for future clinical studies due to its potent inhibitory effect on insulin and glucagon, and its prolonged duration of action.

Animals↗

Evidence for an augmented glucagon dependence of hepatic glucose production in cirrhosis of the liver.

The role of endogenous glucagon in maintaining hepatic glucose production after an overnight fast in patients with cirrhosis of the liver was studied with arterial-hepatic-venous catheterization and using somatostatin to suppress glucagon secretion. Arterial glucagon levels were elevated in eight cirrhotics to 290 +/- 90 pg/ml (SEM) compared to 100 +/- 10 pg/ml (P less than 0.02) in five normal controls, and they were lowered during administration of somatostatin (SRIF; 250 microgram/h) by a mean of 154 pg/ml and 39 pg/ml in cirrhotics and controls, respectively. Basal net splanchnic glucose production (NSGP) was similar in patients with and without cirrhosis (approximately 100 mg/min) but declined more markedly during 30 min of SRIF in cirrhotics to a net splanchnic uptake of glucose of 30 +/- 20 ml/min, as opposed to a fall of NSGP by 44 +/- 2 mg/min in controls (P less than 0.01). To assure that NSGP declined during SRIF infusion due to the fall of glucagon levels, SRIF was combined with a glucagon infusion at 150 ng/m2 . min in four cirrhotics and in five control subjects. Arterial glucagon levels were elevated to a mean of 650 pg/ml and 559 pg/ml in cirrhotics and controls, respectively. NSGP increased after 40 min of SRIF and glucagon replacement to 179 +/- 33 mg/min in cirrhotics and significantly more, to 412 +/- 68 mg/min, in controls (P less than 0.01). Thus, hepatic glucose production during basal and elevated glucagon levels suggested hepatic resistance to glucagon in cirrhosis. Nevertheless, endogenous glucagon played an augmented stimulatory role in maintaining glucose production in the normal range since there was an exaggerated fall of hepatic glucose output during glucagon suppression.

Aged↗

Sampling of arterialized heated-hand venous blood as a noninvasive technique for the study of ketone body kinetics in man.

To determine if sampling of arterialized-hand venous (HV) blood is a suitable alternative for arterial (A) blood to study ketone body metabolism, concentrations of unlabeled and labeled ketone bodies were measured during continuous infusion of 3-14C-acetoacetate in simultaneously drawn samples from A and HV blood in normal subjects. The mean difference of acetoacetate between A and HV blood was in the basal state 1.5% and that of beta-hydroxybutyrate 6% (n.s.). Similarly, the 14C-content of ketone bodies and their calculated rates of production of metabolic clearance were not significantly different between A and HV blood. Following induction of ketosis by acetoacetate loading infusions, the difference of concentrations and 14C-content of total ketone bodies between HV and A blood remained insignificant (average 3%), and ketone body kinetics calculated from A and HV blood were similar. Furthermore, concentrations of glucose, lactate and pCO2 did nit differ significantly between the two sampling sites. In contrast, concentrations of ketone bodies, glucose and pO2 were significantly lower, and the metabolic clearance rate of ketone bodies and pCO2 higher in antecubital venous blood compared to heated-hand venous blood. Thus, the similarity of heated-hand venous and arterial blood suggests that the noninvasive technique is suited for kinetic analyses using tracer methods and for arteriovenous balance studies of ketone bodies.

Acetoacetates↗

[The intranasal provocative test with use of "passive anterior rhinomanometry" in the specific diagnosis of allergic rhinitis].

77 patients with suspected allergic rhinitis to inhalative allergens were studied. Skin tests, RAST determinations and nasal provocation tests, performed by placing a cotton-pledge with aqueous allergen and by "passive anterior rhinomanometry" (PAR), were carried out. This latter test was evaluated by determining nasal resistance and by measuring the temperature variations before and after allergen aerosol inhalation with use of a Heyer-PAR rhinomanometer-sprayer by the method of van Dishoeck. Among 30 hay-fever patients with positive prick tests to grasses or to birch pollens, the overall agreement of PAR with the other allergological diagnostic methods was 90 +/- 5%. Evaluation of a further 47 patients with perennial rhinopathy and suspected allergy to house dust, housedust mite and different molds showed that PAR serves to clarify the allergy diagnosis more reliably than the other methods. The advantages and the negative aspects of PAR are briefly discussed.

Adolescent↗

Validation of a tracer technique to determine nonsteady-state ketone body turnover rates in man.

The features of a single-compartment model of total ketone bodies were evaluated using primed constant infusions of [3-14C]acetoacetate (AcAc) and of D-[3-14C]beta-hydroxybutyrate (beta OHB) in 12 postabsorptive subjects. The volume of distribution (VD) of AcAc was 0.18 +/- 0.01 liter/kg (n = 9), and that of beta OHB was similar, 0.18 +/- 0.02 liter/kg (n = 3). The production rate of total ketone bodies was calculated using the combined specific activity of AcAc and of beta OHB. The mean basal total ketone body production rates were similar using either [14C]AcAc (6.5 mumol . kg-1 . min-1) or [14C]beta OHB (6.8 mumol . kg-1 . min-1). To determine the pool fraction that was rapidly mixed during nonsteady state of ketone body inflow, unlabeled AcAc was infused with stepwise increasing and decreasing rates between 5 and 25 mumol . kg-1 . m-1 to mimic nonsteady-state ketone body production rates. The "functional" pool fraction P was determined as the pool fraction that provided the best match between tracer-determined rates of ketone production and rates of AcAc infusion. P of total ketone bodies was almost equal to 1 using either [14C]AcAc (1.05 +/- 0.16) or [14C]beta OHB (1.00 +/- 0.06), suggesting rapid mixing of ketone bodies throughout the entire pool. The described pool model may be used to determine total ketone body kinetics during acute perturbations of the steady state.

Acetoacetates↗

Effect of somatostatin on splanchnic hemodynamics in patients with cirrhosis of the liver and in normal subjects.

The effect of somatostatin on splanchnic hemodynamics was determined in 8 patients with cirrhosis of the liver and in 18 normal subjects using arterial-hepatic-venous catheterization. Estimated hepatic blood flow determined by indocyanine green infusion was 1.36 +/- 0.23 L/min (+/- SEM) in patients with cirrhosis and remained unaffected during 30 min of somatostatin (250 microgram/h) administration. Wedged hepatic venous pressure which was elevated to 23 +/- 1.8 mmHg was also uninfluenced. In contrast to somatostatin, an infusion of vasopressin (12 U/h for 30 min) given to the same patients, lowered estimated blood flow by 28% (p < 0.05) and wedged hepatic venous pressure by 18% (p < 0.02). Arterial gastrin and insulin levels were lowered during somatostatin infusion by 33% (p < 0.02) and by 75% (p < 0.005), respectively. In contrast to the cirrhosis, infusion of 250 microgram/h somatostatin into normal subjects was associated with a decrease of estimated hepatic blood flow from 1.20 +/- 0.16 to 0.88 +/- 0.12 L/min (p < 0.01) representing a 27% decline. Arterial gastrin and insulin concentrations were lower (p < 0.01) than in cirrhosis, but the basal levels were lowered by somatostatin to a similar degree in both groups of patients. A higher dose of somatostatin (500 microgram/h) administered to normal subjects resulted in a similar decrease of gastrin and of estimated hepatic blood flow as that seen with 250 microgram/h, whereas a lower dose (125 microgram/h) decreased gastrin but failed to influence estimated hepatic blood flow. Thus, somatostatin at a dose which has been used in the treatment of acute peptic ulcer hemorrhage (250 microgram/h) failed to influence estimated hepatic blood flow and wegded hepatic venous pressure in patients with cirrhosis but lowered splanchnic blood flow in normal subjects. Assuming that this effect contributes to somatostatin's therapeutic efficacy, these results cast doubt on its potential value in the treatment of upper gastrointestinal bleeding of cirrhotics with portal hypertension.

Dose-Response Relationship, Drug↗