Nach kombinierter intravenöser Tolbutamid-Secretingabe steigt das radioimmunologisch meßbare Insulin im Serum beim Menschen stärker an als nach alleiniger Tolbutamidgabe. Mit Secretin allein war keine Insulinsekretion zu erzielen. Secretin scheint die Wirkung betacytotroper Substanzen zu potenzieren.

Background: The most frequent sites of metastases in prostatic carcinoma are bones. Bone scintigraphy is the diagnostic tool of first choice for staging bone metastases in cancer of the prostate. But this examination is expensive and time-consuming.Therefore we are looking especially for serum parameters like alkaline phosphatase, the isoenzyme of bone-specific alkaline phosphatase, and prostate-specific antigen (PSA) to replace bone scintigraphy for diagnostic staging. Material and Method: We compared in 132 prostatic carcinoma patients the results of total alkaline phosphatase, bone-specific alkaline phosphatase, and PSA with the results of the bone scan. Results:All three parameters demonstrate a lower sensitivity compared to the bone scan. Although the highest specificity was obtained by bone-specific alkaline phosphatase, this parameter cannot replace the bone scan for staging cancer of the prostate because of a lack of sensitivity. In a subgroup of patients with a PSA level below 10 ng/ml and a total alkaline phosphatase within normal range there is no need to obtain a bone scan, because of the very low incidence of bone metastasis in this group. Conclusions: There is only little additional information if bone-specific alkaline phosphatase instead of total alkaline phosphatase is determined. None of the serum parameters examined can replace bone scintigraphy in staging cancer of the prostate, but PSA and alkaline phosphatase can identify patients who are at low risk for bone metastases.

Die Fragestellung dieser prospektiven Einzelfall-Beobachtungsstudie bei 12 Intensivpatienten war, ob die routinemäßige Bestimmung von Procalcitonin (PCT) bei Intensivpatienten zusätzliche Informationen zum klinischen Befund, zu Routine-Labor-Untersuchungen, zur Mikrobiologie und Radiologie bringt. Bei 12 konsekutiv aufgenommenen Intensivpatienten wurden über durchschnittlich 17,1 (1 bis 35) Tage die PCT-Spiegel bestimmt und mit dem klinischen Verlauf sowie den Ergebnissen der Routine-Diagnostik verglichen.

Treatment of diabetes involves the teaching and education of the patient, increase in his physical activity, regulation of his food intake, self-control of the metabolic situation and - if necessary - medication with oral hypoglycemic agents and insulin.Today the first step in drug treatment of type II diabetics is the prescription of alpha-glucosidase inhibitors or guar preparations. Thereafter, sulfonylurea compounds are indicated. Taking into consideration the contraindications it is possible to combine the biguanid metformin with sulfonylurea compounds. In case of secondary failure of sulfonylurea treatment insulin should be given in addition to the sulfonylurea agents. For insulin treatment, intermediate acting insulins or mixtures of regular and intermediate acting insulins can be given. But it is also possible only to substitute either the prandial need of insulin before the main meals with a short acting regular insulin or the basal need of insulin independently of food intake with a long acting basal insulin. Which kind of insulin regimen will be performed depends on the special problems of each patient.In type I diabetics administration of insulin is necessary. Insulin treatment can be performed as conventional treatment or as intensified treatment according to the so-called >>basis-bolus concept<< or as treatment with insulin-delivery devices. Additionally, for smoothing of spikes in the daily blood-glucose profile alpha-glucosidase inhibitors or guar preparations may be given. Also a combined therapy with insulin and biguanides is possible. Also in type I- as in type II diabetics principally near normal glucose values are aspired. But, keeping in mind the special situation of each patient, so-called treatment targets should be given.

Studies to examine the pharmacokinetics and pharmacodynamic properties of biosynthetic human proinsulin were conducted with the aid of the "glucose-controlled insulin infusion system BIOSTATOR". Seven metabolically normal healthy volunteers were given subcutaneous injections of 0.1 mg human proinsulin per kg body weight, and the subsequent behaviour of the serum proinsulin concentration was monitored over a period of 21 hours. The drop in the blood-sugar levels was counteracted by corresponding infusions of glucose by the BIOSTATOR via a special clamp technique. The intensity and frequency of the glucose infusions given by the BIOSTATOR equipment enable us to draw conclusions regarding the hypoglycaemic efficacy of human proinsulin. Two to three hours after the subcutaneous injection, the serum proinsulin concentration had reached its plateau-like maximum value. After approximately 5 hours it had dropped to 2/3 of the maximum, and after another 3 to 4 hours it had fallen further to 1/3 of the maximum. It returned virtually to its initial value after a total of 14 to 16 hours. The dextrose infusion rate calculated by the BIOSTATOR reflects these changes in the form of an "action profile". Proinsulin has a mean transit time (MTT) of 322 minutes. This is longer than the MTT of normal insulin (188 minutes) but markedly shorter than that of NPH insulin (625 minutes). If the hypoglycaemic effects of insulin and human proinsulin are compared on the basis of the areas under their respective action profile curves, the hypoglycaemic effect of 1 mg human proinsulin corresponds to 5.2 IU insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

40 pmol of biosynthetic human proinsulin was administered to 8 healthy volunteers by intravenous and by subcutaneous route. Following proinsulin administration, venous blood was collected in regular intervals within which proinsulin was determined by a specific radioimmunometric assay with monoclonal antibodies. The proinsulin concentration was determined simultaneously with the insulin and C-peptide radioimmunoassay. Through this investigation the following kinetic parameters were found: The kinetics of the biosynthetic human proinsulin can be best described by the 3-compartment model. The dominant biological half-life was 92 minutes. In intravenous proinsulin administration a proinsulin mean transit time of 80 minutes was found, whereas in subcutaneous administration a proinsulin retention time of 225 minutes was measured. The mean resorption velocity of the subcutaneously applied proinsulin amounted to 145 minutes. Two lag times for subcutaneous resorption can be described, a short one with 9.4 minutes and a long one with 65 minutes. The initial distribution volume for proinsulin was 3.8 l, whereas the distribution volume after complete distribution was 9.3 l. The mean total metabolic clearance was determined with 120 ml/min. Since no difference for the proinsulin concentration was found using the 3 different determination methods a peripheral proinsulin conversion to insulin and C-peptide is not likely. The basal endogenous secretion rate for proinsulin is 68.7 pmol per hour.

Eight volunteers with terminal renal insufficiency having consented to the investigation, were given an i.v. bolus administration of 40 pmol biosynthetic human proinsulin on their dialysis-free day. Intravenous blood for the determination of blood glucose proinsulin, insulin and C-peptide was collected in short intervals for 6 hours and thereafter in longer intervals for 24 hours. Proinsulin was determined by immunoradiometric assay with monoclonal antibodies. The proinsulin kinetics were compared with the kinetics of normal volunteers. The behaviour of proinsulin concentration-time is best described with a 3-compartment model. The dominant biological half-life in terminal renal insufficiency was 6.8 hours which signifies a 4.4-fold increase of the normal half-life. The distribution volumes (V1) in the central compartment do not differ in the two groups, whereas the distribution volume after complete distribution (Vss) is significantly increased in renal insufficiency. The total metabolic clearance in renal insufficiency namely 0.63 ml/kg/min is 2.6 times lower compared to normal subjects with 1.67 ml/kg/min. The extra-renal clearance is 39% of the total metabolic clearance rate, whereas the renal clearance comprises 61%. Peripheral conversion from proinsulin to insulin and C-peptide does not occur in terminal renal insufficiency. The basal endogenous proinsulin secretion rate in renal insufficiency does not differ from that of normal volunteers. The following conclusions can be drawn: 1) Hyperinsulinism observed in renal insufficiency can be explained by circulating proinsulin. 2) In the potential therapeutic use of biosynthetic human proinsulin in diabetics with renal insufficiency dosis adjustment according to the remaining renal function would probably be required.