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Biomedical subjects

B Weber

Publications and source records attributed to B Weber.

At least 397 records · Page 22Linked to original sources

Estimation of urinary unconjugated androstenedione, dehydroepiandrosterone, testosterone, cortisol, aldosterone and 18-hydroxycorticosterone as a potential tool for assessing adrenal status.

A method is described for the simultaneous assay of non-conjugated androstenedione, dehydroepiandrosterone, testosterone, cortisol, aldosterone and 18-hydroxycorticosterone in urine. The method involves solid-phase extraction, automatic high performance liquid chromatography and subsequent radioimmunological quantitation of the individual steroids. Excretion rates of these urinary free steroids were determined in normal males and females. There were no significant sex differences in excretion rates, although both urinary free testosterone and dehydroepiandrosterone were distinctly lower in females than in males. Representative measurements of the excretion rates of patients with Cushing's disease, Addison's disease, ectopic corticotropin syndrome and hirsutism were made. The present method has been shown to be well suited for routine purposes. Its final diagnostic significance for monitoring alterations in glucocorticoid, mineralocorticoid and androgenic activity of the adrenal cortex has yet to be explored.

18-Hydroxycorticosterone↗

[Treatment of diabetic ketoacidosis in children and adolescents].

Despite low mortality rates, diabetic ketoacidosis in children and adolescents remains a potentially fatal condition. In this age group, cerebral edema, rapid decreases of serum potassium levels and severe hypoglycaemia seem to represent the most frequent complications of therapy which have to be avoided. This paper attempts to critically evaluate some greatly different treatment schedules previously published and presents our own experiences with a practicable therapeutic concept which has proved to be simple and safe and only slowly corrects the metabolic deviations. Insulin is administered by continuous intravenous infusion at a rate of 0.1 IU/kg bwt per hour following an initial bolus injection of 0.1 IU/kg. After reduction of blood glucose values to less than or equal to 250 mg/dl, the infusion rate can be reduced to half. For rehydration we use isotonic saline solution at a rate of 100-150 ml/kg body weight and per day, depending on age as far as basal fluid requirements are concerned, and the degree of dehydration, around one half during the first eight hours, the second half during the subsequent 16 hours. Potassium substitution begins after the onset of diuresis, supplying between 3 and 5 mmol/kg body weight during 24 hours. Bicarbonate substitution has proved to be hardly ever necessary and is only used in patients exhibiting the most severe clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increased urinary excretion of free 20 alpha- and 20 beta-dihydrocortisol in a hypercortisolemic but hypocortisoluric patient with Cushing's disease.

We identified non-metabolized, non-conjugated 20 alpha- and 20 beta-dihydrocortisol (20 alpha- and 20 beta-DHF) in urine from a patient with Cushing's disease, by use of three different liquid-chromatographic systems and by gas chromatography-mass spectrometry. We document that these 20-isomers of dihydrocortisol may strongly contribute to unspecific interferences with the immunological assessment of urinary free cortisol (F). The urinary excretion rates of 20 alpha- and 20 beta-DHF were quantified radioimmunologically with use of a cross-reacting cortisol antiserum after effective purification by liquid chromatography. The patient with Cushing's disease had mean peripheral cortisol concentrations of 1018 nmol/L. The urinary excretion rates (nmol/24 h) were 1455 for 20 alpha-DHF, 330 for 20 beta-DHF, and 18 for F. The corresponding reference values (median in nmol/24 h) were 174 for 20 alpha-DHF, 111 for 20 beta-DHF, and 68 for F (n = 22). We conclude that (a) specific estimation of urinary free F is not as highly sensitive for diagnosis of chronic hypercortisolemic states as is generally assumed; and (b) measurement of urinary free 20 alpha- and 20 beta-DHF or of the corresponding 20-DHF:F ratios may be more sensitive.

Adult↗

[Screening of newborn infants for hypothyroidism in Berlin (West) 1978-1982].

In July 1978 a neonatal screening program for congenital hypothyroidism was introduced in Berlin (West) covering more than 98% of the neonates born in the city area. Up to July 1982 TSH was determined on the fifth day of life in 74,350 newborns using a radioimmunoassay for TSH determination in dried blood spots. With a cut-off limit at 20 microU/ml, a control examination was necessary in 0.96% of the newborns. 32 infants with congenital hypothyroidism were detected and treated with 1-thyroxine, giving a total incidence of 1 in 2,323 newborns (permanent and transient cases). 63% of all newborns with elevated TSH levels (greater than 20 microU/ml) were born in the obstetric department of the Neukölln-Hospital, which uses PVP-Iodine for vaginal disinfection of the mothers during labor and delivery, especially after premature rupture of membranes. Those newborns had only transient TSH-elevations, which were normalized on the tenth day of life. The replacement therapy was started on the average on the ninth day of life. The symptoms present in the newborns with congenital hypothyroidism differed from patient to patient and from the "classical" signs of congenital hypothyroidism described in the literature. All infants detected by the screening program are followed in the outpatient department of the Children's Hospital of the Free University in Berlin and show a normal motor and mental development, except for two infants with other causes for retardation in psychomotor development.

Berlin↗

New "on-line" sample-pretreatment procedure for routine liquid-chromatographic assay of low-concentration compounds in body fluids, illustrated by triamcinolone assay.

In this fully automated technique for sample cleanup before chromatographic or other quantitation steps, analytes in body fluids are enriched and semi-purified on a first column. After their selective elution, analytes are "transformed" by admixing appropriate solvents in such a way that they are focused on the top of a second column. By backflush, they then are transferred to an analytical liquid-chromatographic column (or simply eluted for quantification by other techniques). This technique is illustrated by the liquid-chromatographic assay of triamcinolone from a 1-mL urine sample, with ultraviolet detection. Because analytical recovery is almost complete and precision high, no internal standardization is necessary. Interference is eliminated as well as or better than with manual techniques. Chief advantages of this technique are online operation, processing of samples of larger volume, low cost with respect to extraction devices, and nearly universal applicability for exogenous or endogenous compounds of clinical relevance. It potentially may be widely applied.

Body Fluids↗

Diurnal and ultradian variations of plasma concentrations of eleven adrenal steroid hormones in human males.

The diurnal variations of the plasma concentrations of eleven steroid hormones and of corticotropin (ACTH) were studied in ten young healthy males. The plasma steroids progesterone, pregnenolone, deoxycorticosterone, 17-OH-progesterone, 17-OH-pregnenolone, deoxycortisol, 18-OH-deoxycorticosterone, corticosterone, aldosterone, cortisol and 18-OH-corticosterone, as well as plasma ACTH, were measured at 30-min intervals in the morning and in the evening and at 2-h intervals during the rest of the day. Steroids were extracted from 1 ml plasma, fractionated by high-pressure liquid chromatography (HPLC) and finally quantified by radioimmunoassay (RIA). Plasma concentrations of ACTH were radioimmunoassayed after extraction from 2 ml plasma. More or less pronounced circadian and episodic variations were apparent for plasma levels of all steroids studied, as well as of ACTH. According to related profiles of diurnal variations of plasma concentrations, three different categories of steroids were tentatively crystallized. Category 1 includes 17-OH-pregnenolone, deoxycortisol, corticosterone, 18-OH-deoxycorticosterone, deoxycorticosterone, cortisol and 18-OH-corticosterone, exhibiting a rhythm partly synchronous with that of the pituitary secretory activity of ACTH. Category 2, including progesterone, pregnenolone and 17-OH-progesterone, exhibited a time course of plasma concentrations assuming a regulation predominantly dictated by the testicular secretory activity. Lastly, aldosterone exerted a variation of plasma concentrations which was obviously regulated by the renin-angiotensin system under the present conditions.

Adrenal Cortex Hormones↗

Interaction of pseudomonas exoproducts with phagocytic cells.

Polymorphonuclear leukocytes play the major role in host defense against infections with Pseudomonas aeruginosa; however, mononuclear cells also may contribute to defense against pulmonary infections with P. aeruginosa. Therefore, we examined the effects of three extracellular products of P. aeruginosa, exotoxin A, alkaline protease, and elastase, on the function of phagocytic cells. Phagocytosis or killing, protein synthesis, and membrane integrity were used as assays of cellular function. Pseudomonas toxin readily inhibited protein synthesis in mouse peritoneal macrophages; in contrast, proteolytic enzymes did not alter protein synthesis, but transiently decreased the sensitivity of macrophages to toxin. High levels of toxin reduced protein synthesis in human peripheral polymorphonuclear leukocytes but did not alter the ability of these cells to kill P. aeruginosa. Elastase and alkaline protease did not cause release of marker enzymes and did not directly inhibit the bactericidal activity of polymorphonuclear leukocytes; killing was reduced due to inactivation of complement components. In conclusion, these potential virulence products do not modify phagocyte function directly and thus do not directly interfere with host response in pseudomonas infections.

Animals↗

Single dose kinetics of mefloquine in man. Plasma levels of the unchanged drug and of one of its metabolites.

Oral single dose kinetics of mefloquine was investigated in 16 male volunteers, 3 Caucasians and 13 African natives. Unchanged mefloquine (= M) and one of its metabolites (= MM) were measured in the plasma. The apparent half-life of absorption of M ranged from 0.36 to 2.0 h, its terminal half-life of elimination from 15 to 33 days. Assuming complete systemic availability, an apparent volume of distribution of 14-29 liters x kg-1 and a total clearance of 18-39 ml x min-1 were derived. MM given orally to mice or rats showed at equal dose the same tolerance as mefloquine. Following oral administration of M to man, plasma levels of MM surpassed those of M, resulting in a 2.4-5.1 larger AUC. However, because of its much smaller apparent volume of distribution, MM may be anticipated to represent only a small percentage of the dose and therefore to contribute only to a minor extent towards the unwanted side effects of the drug.

Adult↗

[Criteria of good metabolic control in children and adolescents with diabetes mellitus (author's transl)].

Treatment of insulin-dependent children and adolescents is aimed at normalizing the metabolism without harming the patient, and to avoid the development of secondary vascular and neural changes. On the other hand, however, therapy has to cope with limited possibilities to optimize insulin substitution and to achieve normal metabolic regulation. Therefore, criteria of "good" metabolic control differ, depending on whether they relate to a desirable or to an acceptable metabolic regulation. Actual therapeutical achievements rarely meet initial expectations. Paediatric diabetologists seem to fairly well agree on the criteria of an acceptable metabolic control of insulin-dependent children and adolescents, i.e. freedom of symptoms, normal growth and development, glucosuria of less than 20 g/d or of 5-10% of carbohydrate intake, and pre- and postprandial blood glucose levels of less than 150 and less than 200 mg/dl, respectively, in greater than or equal to 75% of the observation time. Concentrations of glycosylated haemoglobin (Hb A1) of less than 11% (total, microcolumn technique), and less than 10% (stable fraction) seem to fairly well correspond to the indicated blood glucose level of less than 200 mg/dl.

Adolescent↗

[Urine glucose monitoring at home becomes easier and more precise with a new test-tape: diabur-test 5000 (author's transl)].

In paediatrics, the daily determination of glucose excretion is considered to be one of the major tools for the evaluation of metabolic control in diabetic children and adolescents. Large amplitudes of glucosuria from 0% to greater than 5% in this age group, however, require test methods sufficiently precise and easy to perform, the results of which may, in fact, permit to draw therapeutic consequences. Recently, a new test-tape using an enzymatic method of glucose determination has been developed Diabur-Test 5000 Boehringer Mannheim GmbH), which fulfills these requirements. In 219 urine samples, tested by a paediatric nurse practitioner, the correlation coefficient of glucose values determined by both this tape and a hexokinase reference method was found to be good: r = 0.995 (p less than 0.001). Both concerning the simplicity of performance and the precision of results, Diabur-Test 5000 proved to be superior to the well-known Clinitest-2-drop method (correlation to hexokinase method: r = 0.791 (p less than 0.001). In the hands of patients, this semiquantitative method proved to be somewhat less but still sufficiently precise to be recommended for urine glucose monitoring in diabetic children and adolescents.

Adolescent↗