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M Berger

Publications and source records attributed to M Berger.

At least 1,243 records · Page 69Linked to original sources

Biologic activity and pharmacokinetics of biosynthetic human insulin in the rat.

The biologic potency (plasma glucose depression) of pancreatic human insulin was compared with that of biosynthetic human insulin (BHI), manufactured by recombinant DNA techniques in bacteria, following intravenous injection in rats. The specific activity of the pancreatic human insulin was 32 U/mg, while that for BHI was 27 U/mg. These values were not significantly difference, but were higher than the value for pancreatic pork insulin (25 U/mg). The pharmacokinetics of i.v. injected A14-mono-125I-insulin (pork) were found to be similar to those observed for semisynthetic [3H]insulin (pork), the respective metabolic clearance rates (MCR) being 20.8 +/- 0.8 ml/min/kg (N = 4) and 23.6 +/- 1 ml/min/kg (N = 5) (P greater than 0.1). The MCR for A14-mono-125I-BHI was 24.6 +/- 2.2 ml/min/kg (N = 4), which was significantly higher (P less than 0.025) than the value for A14-mono-125I-pork insulin. BHI is thus no less active than pork insulin in rats and possibly somewhat more active. The small difference in activity may be due to increased affinity for rat insulin receptors, resulting in a more rapid MCR for BHI. In addition, the A14-monoiodinated insulin tracer used in these studies is indistinguishable from semisynthetic [3H]insulin in terms of its rate of clearance, indicating that the insulin molecule has not suffered any iodination damage and is thus a valid tracer for metabolic and receptor studies.

Animals↗

Absorption kinetics and biologic effects of subcutaneously injected insulin preparations.

This paper describes systematic studies on the absorption kinetics of exogenous insulin from its subcutaneous tissue depot in 52 male nonobese volunteers (age 20-30 yr). Five experimental protocols were used: effect of changing injection site, effect of temperature change and local massage, effect of aprotinin and human serum, effect of mixing regular insulin with long-acting insulin preparations, and effect of temperature change, muscular exercise, and local massage on the absorption of long-acting insulin preparations. The fastest absorption of insulin occurred at the abdominal injection. Absorption after arm injection was faster than after thigh injection. A hot bath and local massage dramatically increased serum insulin levels in the first 90 min after injection; in contrast, a cold bath delayed absorption substantially. Both aprotinin and the subjects' own blood serum mixed with insulin caused a marked acceleration of the insulin absorption process. Absorption kinetics of two neutral regular insulins (Actrapid and Leo Regular) were virtually identical. Mixing Actrapid with Monotard caused higher serum insulin levels than the mixture of Leo Regular with NPH. A time lag of 5 min between the mixing of Actrapid and Monotard and the injection caused a delayed rise of serum insulin levels; in contrast, this delay could not be observed when Leo Regular and NPH were mixed. Volunteers performed bicycle exercise, applied a hot water bottle to the injection site, or rubbed the injection site 2 1/2 h after injection of long-acting insulin. Accelerated absorption of insulin was only observed after local massage of the injection site of Monotard, Leo NPH, and Mixtard. Local heat had no effect. Exercise caused only an increased absorption of insulin after the Mixtard injection but not after Monotard or NPH injection. These findings have clinical significance and should not be without potential benefit in the attempt to improve metabolic control in insulin-treated diabetic patients.

Adult↗

Absorption kinetics of semisynthetic human insulin and biosynthetic (recombinant DNA) human insulin.

Absorption kinetics of subcutaneously injected human insulin (recombinant DNA) and semisynthetic human regular insulin were investigated and compared to the respective porcine insulin preparations in normal volunteers. The absorption of all regular human insulin preparations tested was accelerated as compared to porcine insulins. The clinical relevance of these findings in regard to the treatment of diabetes mellitus appears to be doubtful. As for mixtures of porcine regular and intermediate-acting insulin preparations, the absorption of human regular insulin is not altered when mixed with intermediate-acting human insulin.

Absorption↗

Diet liberalization and metabolic control in type I diabetic outpatients treated by continuous subcutaneous insulin infusion.

In 10 type I diabetic outpatients treated by continuous subcutaneous insulin infusion (CSII), dietary habits and metabolic control were investigated. Under conditions of a conventional diabetes diet (including 5-6 meals per day and a strictly planned meal intake) as well as under a "less restricted diabetes diet" (e.g., free choice of number, timing, and amount of carbohydrate intake) near normoglycemia could be achieved. Mean daily blood glucose levels did not change significantly when the patients' nutrition was alternated between both diets. During the "less restricted diabetes diet," the patients opted for a rather high fat intake (51 +/- 5% fat, 34 +/- 5% carbohydrate, and 15 +/- 2% protein). Despite this unintended dietary behavior, serum lipids and body weight remained normal after an observation period of 4-6 mo. It is concluded that during permanent near normoglycemia achieved by CSII a partial liberalization of the diabetes diet does not introduce any short-term or long-term metabolic risk factors for cardiovascular diseases.

Adolescent↗

Pharmacokinetics and bioavailability of injected glucagon: differences between intramuscular, subcutaneous, and intravenous administration.

Pharmacokinetics and bioavailability of 1 mg glucagon injected intramuscularly (i.m.), subcutaneously (s.c.), or intravenously (i.v.) were studied in 6 nondiabetic men rendered hypoglycemic by s.c. injection of 10 U regular insulin. At 90 min after the insulin injection, when blood glucose levels had fallen to a mean of 49 mg/dl, glucagon was administered. Ten minutes later plasma glucagon levels had risen from a mean of 246 to 3233 pg/ml (s.c. experiment) and from 250 to 2638 pg/ml (i.m. experiment). Accordingly, there was no difference in blood glucose behavior whether glucagon was injected s.c. or i.m. In the i.v. experiment, plasma glucagon levels were significantly higher during the first 15 min after the glucagon injection when compared with the other experiments. The initially high levels of plasma glucagon after i.v. administration were associated with a steeper rise of glycemia during the first 5 min after glucagon injection; the maximal increase of blood glucose was, however, not different when compared with the s.c. or i.m. route of glucagon administration. Thus, in case of severe hypoglycemia, therapeutically administered glucagon will be most efficient when injected i.v., but there is no difference between the i.m. and s.c. routes of administration with regard to the efficacy to increase blood glucose levels.

Adult↗

Incidence and management of severe hypoglycemia in 434 adults with insulin-dependent diabetes mellitus.

The risk of severe hypoglycemia associated with the particular therapeutic approach of two University hospitals was assessed in 96% of all patients with insulin-dependent diabetes mellitus (IDDM) who had been admitted during a period of almost 3 yr to the diabetic wards of two hospitals and who participated in a structured teaching and treatment program. During a mean follow-up period of 18 mo, 10% of the conventionally treated patients (N = 384; age 30 +/- 13 yr; duration of diabetes 12 +/- 9 yr) and 9% of the CSII-treated patients (N = 50, age 28 +/- 7 yr, duration of diabetes 13 +/- 7 yr, total follow-up period 1093 patient-mo) experienced at least one severe hypoglycemic episode per year, and a total of 123 severe hypoglycemic episodes occurred. In a subgroup of 169 conventionally treated patients, mean glycosylated hemoglobin values decreased from 10.5 +/- 1.9% before participation in the program to 9.2 +/- 2.0% (P less than 0.001) 18 +/- 4 mo thereafter. For the CSII-treated patients, glycosylated hemoglobin values were 9.7 +/- 1.9% before initiation of pump therapy and remained at the upper normal range from 3 mo thereafter throughout the study. There was no relationship between glycosylated hemoglobin levels and the occurrence of severe hypoglycemic episodes. Fifty-three severe hypoglycemic episodes were treated with glucagon injections by the patients' relatives (all but one effectively), 30 were managed by assisting physicians, and 44 led to hospitalization. Thus, successful attempts to improve glycosylated hemoglobin values in an unselected group of patients with IDDM were not associated with an unduly high risk of severe hypoglycemia when compared with the scarce data from the literature.

Adolescent↗

Prolongation of survival of rats injected with hepatoma cells treated by nuclei extracts from mouse and rat embryo cells.

Cancer cells express particular genes, part of which are normally active during the embryonic development. On the other hand, young embryos are able to differentiate teratocarcinoma or leukemia cells, likely by producing differentiation factors. In this work, rat and mouse embryo cell nuclei extracts were tested on hepatoma carcinoma cells LFCl2A: they inhibit the cell growth in culture and increase the survival of syngeneic rats injected with hepatoma cells incubated with these extracts. This inhibition is correlated with a decrease of DNA synthesis without toxic effect: It seems to be due to the mixture of tight binding DNA proteins, possibly transcriptional factors.

Animals↗

Individual fecal alpha 1-antitrypsin excretion reflects clinical activity in Crohn's disease but not in ulcerative colitis.

BACKGROUND/AIMS: The natural course of fecal alpha 1-antitrypsin (AAT) excretion was assessed in patients with inflammatory bowel disease (IBD) to evaluate its role in monitoring their clinical disease activity. METHODOLOGY: A prospective cohort pilot study was performed in 9 patients with Crohn's disease (CD) and 3 individuals with ulcerative colitis (UC). Subjects were investigated at regular monthly intervals for about one year for (a) parallel AAT stool and serum concentrations by standard immunonephelometry, and (b) for clinical disease activity by Crohn's Disease Activity Index (CDAI) in CD patients, and by Clinical Activity Index (CAI) in UC subjects. Absolute results during follow-up were each referred to individual findings at study entry as relative results. RESULTS: While absolute fecal AAT concentration did not correlate with disease activity indices (p > 0.26), relative fecal AAT concentration significantly correlated to concurrent relative CDAI score in CD patients (p < 0.001, r = 0.67), but not to relative CAI score in UC subjects (p = 0.92). Monthly intraindividual variation of fecal AAT excretion did not predict development of either disease activity index (p > 0.14). CONCLUSIONS: Individual fecal AAT excretion closely reflects clinical course in CD subjects, but not in UC patients. It does not predict symptomatic deterioration in these individuals, at least on a short-term basis.

Adult↗

Whiplash injuries: clinical picture and diagnostic work-up.

The term "whiplash" commonly refers to symptoms and signs associated with a mechanical event such as a sudden acceleration and deceleration of the neck (due, in the majority of cases, to a road accident), instead of to the mechanism itself. The recent Quebec Classification of Whiplash Associated Disorders (WAD) contributed to define nosographically all the clinical manifestations usually grouped under the terms acute/post-traumatic and late "syndrome". In the late phase of WAD, neck pain and neck muscle contraction have been reported in all cases, together with headache in over 50%. "Headache stemming from the neck", despite numerous attempts to classify this entity (i.e. cervicogenic headache) according to the IASP classification (headache associated with neck disorders), is still a subject of debate. An adequate multiparametric procedure is required to study WAD, which takes into account: the patient's principal details; an exact reconstruction of the event; description and analysis of the signs and symptoms, with various complications and correlated dysfunctions; an objective neurological and neck-shoulder examination; and a battery of complementary instrumental tests which are described in this study. These investigations include evaluation of muscle tension (manual palpation, algometry, EMG recording), kinematic analysis of the cervical spine, neuropsychological and psychological evaluation, and evaluation of disability. In order to assess cervical spine mobility in WAD patients, a 3D kinematic analysis by means of the ELITE system and clinical evaluation were performed in our setting. Seventy patients with whiplash injury and 46 healthy volunteers were enrolled in the study. Patients were tested at the time of first consultation and again 6 months and 12 months later. Clinical evaluation of the range of motion was performed both in patients and in 41 healthy volunteers. Furthermore, patients diagnosed according to the WAD Classification as grade 2 (n = 68) or grade 3 (16) underwent a Quality of life (QoL) evaluation, measured using the short form (36-item) Health Survey (SF36) and the migraine-specific questionnaire (MSQ). According to our data, whiplash patients showed an impairment of cervical spine mobility, as well as a poor QoL, compared to a control group population, even though we observed a trend towards improvement over time in cervical ROM.

Biomechanical Phenomena↗

Cholinergic and noradrenergic neurotransmission: impact on REM sleep regulation in healthy subjects and depressed patients.

The reciprocal interaction model of NonREM- and REM sleep regulation suggests that the cycling alternating pattern of Non-REM- and REM sleep is under the control of noradrenergic/serotonergic and cholinergic neuronal networks. This model was tested in healthy humans by administration of cholinergic agonists/antagonists and noradrenergic antagonists prior to or during sleep. Cholinomimetics like physostigmine, RS 86 and galanthamine provoked an earlier onset of REM sleep, whereas subchronic treatment with scopolamine, a cholinergic antagonist, only led to a heightening of REM density. Simultaneous administration of noradrenergic antagonists with a cholinergic agonist did not provoke a more pronounced REM sleep advance. Comparative studies with the cholinergic agonist RS 86 in depressed patients, schizophrenic patients and patients with other psychiatric disorders revealed the most pronounced REM sleep response in the depressed group. The REM sleep response to cholinergic stimulation in depression did however not predict the treatment response to a differential-therapeutic strategy.

Adolescent↗

Accuracy of blood glucose self monitoring in elderly insulin treated diabetic patients.

We investigated the accuracy of blood glucose self monitoring in 131 patients (mean +/- SD age 65 +/- 7 years, duration of diabetes 11 +/- 6 years) who participated in a 5-day inpatient group treatment and teaching programme especially designed for elderly insulin-treated patients. Patients' estimations and laboratory blood glucose measurements were compared on day 1 (after theoretical and practical introduction into blood glucose self monitoring) and on day 4 of the programme. Patients were trained in the visual reading of Haemoglukotest 20-800R; blood glucose meters were recommended only exceptionally. Error grid analysis showed a high accuracy of visually assessed blood glucose values, both on day 1 (94% of measurements in zone A, 5% in zone B) and on day 4 (95% in zone A, 4% in zone B). Patients with no prior experience in blood glucose self monitoring (n = 67) showed a significant improvement (p less than 0.02) in accuracy from day 1 to day 4. Values determined by blood glucose meters were less accurate, although this trend did not reach statistical significance. A second group of 94 consecutive patients was reexamined 5 years after participation in the treatment and teaching programme. 55 patients were still alive and 42 could be evaluated. Accuracy of blood glucose estimations was assessed in all 26 patients practising blood glucose self monitoring (age 69 +/- 5 years, diabetes duration 18 +/- 8 years), either at their homes (n = 23) or at our diabetes outpatient clinic (n = 3). Error grid analysis showed a high accuracy by visual reading (n = 21, 95% zone A, 5% zone B).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Sexual abuse in the family].

The article gives an overview of various aspects of sexual abuse of female and also male children and adolescents in their families. Exposure, frequency and definition and also questions regarding the psychic consequences of sexual abuse are discussed. Special psychodynamic aspects in the families and therapeutic possibilities are also dealt with.

Child↗