EASD postgraduate courses in middle and eastern Europe 1991-1995: an experience of solidarity.
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Diabetes Mellitus↗
Biomedical subjects
M Berger
Publications and source records attributed to M Berger.
Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients.
Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD) and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this study, we investigated the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Using the Bielschowsky silver-staining method, we were able to differentiate between four types of plaques described earlier: diffuse, primitive, classic and compact. While diffuse plaques represent the early stage of plaque formation, primitive and classic plaques are thought to represent later stages of plaque development. We investigated serial sections of paraffin-embedded cortices of ten clinically diagnosed and histopathologically confirmed AD patients and ten patients with no clinical history of dementia. We found plaques in the brains of both nondemented and demented persons using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the group of clinically nondemented persons, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger portion of lesions in the group of AD brains. IL-6 could not be detected in plaques of patients without dementia. Many IL-6-positive plaques were found in six of the AD brains and to a smaller extent in the other four AD cases. In the six cases with a large number of IL-6-positive plaques, IL-6 was found in a significantly higher ratio of diffuse plaques than expected from a random distribution of IL-6 in all plaque types.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Tumor vaccines: effects and fate of IL-2 transfected murine melanoma cells in vivo.
We have previously demonstrated the general usefulness of the adenovirus-enhanced transferrinfection (AVET) in the generation of IL-2 producing tumor vaccines. By optimizing different parameters of the transfection protocol we were able to transform the poorly immunogenic M-3 mouse melanoma cell line into a potent immunogen. A long-lasting immunity was demonstrated after administration of the IL-2 releasing vaccine, since immunized animals successfully rejected native M-3 melanoma cells even after a period of more than 6 months. We also demonstrated that in vivo administration of such a vaccine is safe since transmission of the transfected IL-2 gene in host organs was not detected. IL-2 production ceased 2 days after injection because the engineered cells were destroyed. However, RT-PCR analysis of the site of vaccine injection suggests that IL-2 exerts its effects not only directly but also by inducing a set of other immunomodulator cytokines in situ that are probably indispensable in inducing a host response. We conclude that AVET of IL-2 into tumor cells is a safe and efficient method for the generation of tumor vaccines.
Adenoviridae↗
Effects of the serotonin-1A agonists buspirone and ipsapirone on field potentials in the hippocampus slice: comparison with carbamzepine and verapamil.
The serotonin-1A agonists buspirone (BU) and ipsapirone (IPSA) have been demonstrated to exert antidepressant and anxiolytic effects. Since some antidepressant drugs and the antiepileptic substance carbamazepine have calcium antagonistic properties, the interaction of BU and IPSA with carbamazepine and the organic calcium channel blocker verapamil was analyzed in the low Mg2+ induced model epilepsy which has been shown to be suppressed specifically by organic calcium antagonists. BU and IPSA reduced the frequency of occurrence of low magnesium induced field potentials in CA1 and CA3 areas of the hippocampus slice preparation (guinea pigs) in a dose dependent manner. The subthreshold concentrations which yielded no effect were 5 mumol/l for BU and IPSA, 10 mumol/l for carbamazepine and 2 mumol/l for verapamil. Combinations of these subthreshold concentrations elicited a reduction in the repetition rate of field potentials. The results indicate that BU and IPSA behave additively with verapamil and carbamazepine, which may be due to a common action on the same subtype of calcium channels. It may be assumed that besides their action on 5-HT1A receptors BU and IPSA may also have calcium antagonistic properties.
Animals↗
Marked PR interval prolongation simulating ST-segment elevation during exercise testing. A case report.
ST-segment elevation during exercise testing is usually indicative of severe proximal coronary artery disease. In this report, the authors describe a patient who underwent exercise stress testing and developed apparent ST elevation in the inferolateral leads. However, noninvasive imaging studies revealed no evidence of myocardial ischemia or other recognized causes of this exercise electrocardiographic (ECG) finding. Analysis of the ECG tracings showed that ST elevation was produced by marked prolongation of the PR interval, super-imposing the P wave on the J-junction of the preceding QRS-ST-segment complex. The authors suggest that marked PR prolongation during exercise may mimic ST elevation, and this possibility should be considered in patients with this exercise ECG finding in whom cardiac evaluation is negative.
Aged↗
Growth-hormone response to clonidine in panic disorder patients in comparison to patients with major depression and healthy controls.
Growth-hormone (GH) responses to the alpha 2-adrenoceptor agonist clonidine were measured in 9 panic disorder patients, in 9 patients fulfilling DSM-III-R criteria for major depressive episode, and in 9 age- and sex-matched controls. GH responses to clonidine were not significantly different between the groups. The data do not agree with the assumption that blunted GH responses to clonidine represent a general feature of panic disorder or major depression.
Adrenergic alpha-Agonists↗
A seizure, and electroencephalographic signs of a lowered seizure threshold, associated with fluvoxamine treatment of obsessive-compulsive disorder.
A 38-year-old patient with severe obsessive-compulsive disorder received fluvoxamine in a clinical study. Psychometric ratings showed marked clinical improvement in the third week of fluvoxamine administration, but after 8 weeks, at a dose of 300 mg per day, he suffered a grand mal seizure after drinking a glass of beer (0.2 liter). He had no history of previous epileptic seizures. Careful neurological evaluation including computer tomography and magnetic resonance imaging of the brain revealed no signs of acute disease. EEG before the fit did not show epileptiform activity; after the fit, spikes and spike-wave complexes appeared, which disappeared upon discontinuation of fluvoxamine. Since his obsessive-compulsive symptoms had responded well to fluvoxamine and worsened after its discontinuation, the drug was cautiously reintroduced. Improvement of the obsessive-compulsive symptoms was observed again, but spikes and spike-wave complexes reappeared at a dose of 50 mg per day. Under anticonvulsant treatment with carbamazepine, fluvoxamine was increased to 100 mg per day. No seizures occurred during a follow-up to two years.
Adult↗
Effect of 4-hour hyperglycaemia and hyperinsulinaemia on plasma atrial natriuretic factor concentrations.
To elucidate the mechanism behind the increased plasma atrial natriuretic factor (ANF) reported in Type 1 diabetic patients with glomerular hyperfiltration and incipient nephropathy, we studied the effects of a short-term moderate hyperglycemia with concomitant hyperinsulinaemia on plasma ANF concentrations and glomerular filtration rate (GFR) in healthy male volunteers. Following a 2-hour basal run-in period, blood glucose level was clamped at 12.2 mmol/l for 4 hours by infusing 20% glucose solution (hyperglycaemia study) or the level was kept normal by infusing isotonic saline over the 4 hours (saline control study). Plasma ANF increased slightly both in the hyperglycaemia phase (from 25.7 +/- 6.3 to 32.1 +/- 7.5 ng/l at 3 hours [p < 0.02] and 31.0 +/- 6.6 ng/l at 4 hours [p = 0.058, mean +/- SD]) and in the control phase (from 17.7 +/- 6.1 to 26.1 +/- 13.5 ng/l at 3 hours [p < 0.05] and 25.4 +/- 11.7 ng/l at 4 hours [p < 0.05]) as compared with the respective baseline values. GFR remained unchanged both in the hyperglycaemia (from 108 +/- 8 to 104 +/- 13 ml/min/1.73 m2) and the saline control phases (from 106 +/- 7 to 101 +/- 7 ml/min/1.73 m2), respectively. The results of this short-term study showed no association between the moderate hyperglycaemia with a concomitant hyperinsulinaemia and plasma ANF concentration in non-diabetic normotensive subjects.
Adult↗
[Treatment of depression with sleep deprivation and sleep phase advancement].
Total sleep deprivation (TSD) exerts beneficial but only transient effects on mood in approximately 60% of the patients with a major depressive disorder (MDD). The positive effect of TSD is generally reversed after the next night of sleep. A pilot study of our group indicated that a consecutive one week phase advance of the sleep phase stabilized mood in more than half of the patients who responded to TSD. However, the majority of patients in our pilot study had been treated concomitantly with antidepressive medication. To exclude a possible synergistic effect of simultaneous antidepressive medication and the sleep-wake manipulation in the present study eleven medicated and sixteen drug-free depressed patients were investigated. In two thirds of the patients relapse into depression after successful TSD could be prevented. This effect seemed to be independent of adjunct antidepressant pharmacotherapy. Ten of these patients were studied polysomnographically prior to and during the treatment. Data analysis revealed that during the advance of the sleep phase no prolonged partial sleep deprivation took place. At the end of the study REM % had even increased and REM latency was still short in spite of clinical improvement, thus contradicting the assumption that REM sleep suppression is a necessary prerequisite for antidepressive therapy. The results support the hypothesis of a "critical phase" in the morning hours during which sleep can reinduce depressive mood and, vice versa, prevention of sleep during this time may act antidepressively.
Adult↗
Cross-sectional and longitudinal studies of naturally occurring antibodies to Pseudomonas aeruginosa in cystic fibrosis indicate absence of antibody-mediated protection and decline in opsonic quality after infection.
Most patients with cystic fibrosis (CF) develop chronic endobronchial infection with mucoid Pseudomonas aeruginosa. It has been suggested that opsonic antibodies to the mucoid exopolysaccharide of P. aeruginosa protect older CF patients (> 12 years of age) who have remained free of colonization by this organism. Serum antibodies from chronically infected CF patients had greater total complement-dependent opsonic activity than did those of older noncolonized patients (P < .02), but when bound antibody was equalized, opsonic quality was greater for the latter group (P < .03). In longitudinal studies, antibody titers to mucoid P. aeruginosa rose greatly after initial infection, but opsonic quality declined (P = .002). Twenty CF patients who passed age 12 free of P. aeruginosa colonization developed chronic P. aeruginosa lung infection at ages 14-35 years. Thus, naturally occurring antibodies do not protect CF patients from P. aeruginosa infection, and opsonic quality of serum antibodies deteriorates as infection becomes established.
Adolescent↗
Intensified antihypertensive therapy is associated with improved survival in type 1 diabetic patients with nephropathy.
OBJECTIVE: To determine the prognosis of treated hypertensive type 1 (insulin-dependent) diabetic patients with overt nephropathy. DESIGN: A controlled, prospective, parallel, 5-year follow-up trial. SETTING: The tertiary care centre of the Heinrich Heine University Hospital in Dusseldorf, Germany. PATIENTS AND INTERVENTIONS: A sequential sample of 91 hypertensive patients with overt diabetic nephropathy participated in a diabetes treatment programme. Thereafter 45 patients received intensified antihypertensive therapy including blood pressure self-monitoring and self-adjustment of antihypertensive drug treatment with the goal of permanent normalization of blood pressure values below 140/90 mmHg. The remaining 46 patients were administered routine antihypertensive therapy and formed the control group. At baseline both groups were comparable in age, sex, metabolic control and renal function. The groups differed at baseline in their duration of diabetes and blood pressure values, which were higher in the intensified antihypertensive therapy group. OUTCOME MEASURES: Total mortality and the need for renal replacement therapy. MAIN RESULTS: Blood pressure control was significantly improved in patients who were subjected to intensified antihypertensive therapy, whereas it deteriorated in the group of patients who received routine antihypertensive therapy. At follow-up, primary end points of the study occurred in five (11%) patients of the intensified therapy group and in 19 (41%) patients of the routine therapy group. According to life table analysis, intensified antihypertensive therapy was associated with less frequent primary end points (P = 0.0058) and longer survival (P = 0.01). The differences between the groups remained significant after adjustment for covariates in the proportional hazards model. CONCLUSION: Participation in a treatment programme aimed at intensification of antihypertensive therapy is associated with a reduction of mortality in hypertensive type 1 diabetic patients with overt nephropathy.
Adult↗
CD34+ cell immunoselection from G-CSF-alone-primed peripheral blood in children with low body mass.
We report the data of CD34+ cell immunoselection from peripheral blood after G-CSF-alone mobilization (10 micrograms/kg/d s.c.) in nine children with neuroblastoma (median age 4-5 years (2-8), median body weight 16 kg (10-20). Leukaphereses were carried out on a Cobe Spectra separator and two consecutive harvests (4 blood volumes processed) were used for immunoselection on a Ceprate column. The yield of CD34+ cells in the purified fraction was 50% (23-80), with a median number of 2.8 x 10(6) CD34+ cells/kg (1-9.4). All patients were reinfused with selected CD34+ cells after busulfan 600 mg/m2 +melphalan 180 mg/m2 and achieved successful haemopoietic recovery.
Antigens, CD34↗
Liberalized diet in patients with type 1 diabetes.
OBJECTIVE: To document that strict dietary regimen are not necessary in the context of intensified insulin therapy. DESIGN: German multicentre, prospective cohort study; 6 years follow-up. SETTING: Ambulatory examination using a mobile ambulance. SUBJECTS: A total of 636 type 1 diabetic patients (age 33 +/- 7 years, diabetes duration 15 +/- 7 years; mean +/- SD), who had participated in a structured, 5-day, in-patient, group treatment and teaching programme for intensification of insulin therapy and liberalization of the diabetes diet 6 years prior to follow-up. MAIN OUTCOME MEASURES: Relations between the extent to which patients practise a liberalized diet, the degree of metabolic control (HbA1c, severe hypoglycaemia, body mass index, cholesterol), and the patients' perceived burden through dietary treatment. RESULTS: In the total patient group, HbA1c was 7.9 +/- 1.6%, and the incidence of severe hypoglycaemia was 0.17 cases per patient during the preceding year; 31% patients injected insulin < or = 3 times per day, 58% 4-7 times per day, and 11% used insulin pump therapy. Only 11% patients reported following a meal plan, whereas 89% continually changed timing and amount of carbohydrate intake; only 5% had the same number of meals every day, whereas as many as 20% varied the number of meals per day by four or more; 53% skipped main meals; 85% habitually consumed sugar or sugar containing foods. Patients with a higher degree of diet liberalization injected insulin or used an insulin pump therapy more frequently, and perceived their dietary treatment to be less burdensome. No clinically significant associations were found between the extent of diet liberalization and metabolic control. CONCLUSIONS: Under the conditions where type 1 diabetic patients have the opportunity to participate in an intensified insulin treatment and teaching programme, liberalization of the diabetes diet is not associated with adverse effects on glycaemic control, but is associated with less perceived burden through dietary treatment.
Adult↗
Mortality and morbidity in treated hypertensive type 2 diabetic patients with micro- or macroproteinuria.
In order to describe the natural history of high risk diabetic patients treated for hypertension we have followed a sequential sample of 100 hypertensive Type 2 diabetic patients with elevated urinary protein excretion ( > or = 60 mg 24 h-1) for a period of 1-7 years. Antihypertensive treatment was instituted in all patients and, in addition, the patients were offered the possibility of participation in an intensified antihypertensive therapy programme. After a mean follow-up of 4 years overall mortality was 13%. Nineteen percent of all patients experienced a cardiovascular event and 7% a cerebrovascular event. In conclusion, in this study the overall mortality was lower that previously reported in proteinuric Type 2 diabetic patients. Antihypertensive treatment may account for this outcome.
Age Factors↗
Implementation of intensified insulin therapy: a European perspective.
The Diabetes Education Study Group (DESG) of the European Association for the Study of Diabetes (EASD) was founded in 1979 with its major goal to make effective patient training an integral part of any diabetes therapy. Within the DESG, a number of models for structured diabetes treatment and teaching programmes were developed. Concerning the care of persons with Type 1 diabetes, substantial emphasis was placed upon the 5-day in-patient treatment and teaching programme for groups of 6 to 10 patients as originally introduced at the University of Geneva and further developed for general use at the University of Düsseldorf. During the early 1980s, this programme was based upon intensified insulin therapy including a stepwise liberalization of previously rigid rules for nutrition and life schedules. In several European centres the programme was continuously evaluated and shown to be effective as documented by significant reductions of glycated haemoglobin values, episodes of ketoacidosis, hospitalizations, and sick-day leaves. In contrast to the Diabetes Control and Complications Trial (DCCT) the improvement of glycated haemoglobin values was not associated with an increased risk of severe hypoglycaemia. Possible reasons for this favourable outcome are discussed. During recent years the 5-day treatment and teaching programme for Type 1 diabetes has been translated into the general health care system of Germany without any loss of its efficacy. In addition, in various other European countries, model centres of diabetes care have implemented the 5-day programme, and for a number of these centres, its efficacy to improve the overall quality of diabetes care has been published or presented at meetings.
Albuminuria↗
Outcome at three years of sick neonates involved in a double-blind trial of two parenteral amino acid preparations.
The authors investigated the hypothesis that neonates who received a parenteral amino acid preparation causing high plasma amino acid levels in the first week of life would perform less well at follow-up than those who received a preparation in which the plasma aminogram fell persistently within the normal range. 27 surviving children who had received either preparation as neonates underwent psychometric assessment at three years. Parents completed three questionnaires about temperament, behaviour screening and socio-economic status. Four of 10 patients who had received one preparation and two of 17 infants who had received the other were of below-average intelligence. This may be related to the different amino acids in the mixtures and the hyperamino-acidaemia caused by this.
Amino Acids↗
Mental comorbidity of chronic insomnia in general practice attenders using DSM-III-R.
The major aim of this study was to investigate links between chronic insomnia and mental and personality disorders using the DSM-III-R classification. Of a sample of 2512 general practice attenders, 105 with a chronic insomnia complaint over a 4-month period were evaluated for mental and personality disorders. In addition, the significance of other factors such as personality traits, social functioning and the patient's own estimation of sleep quality was studied. Sixty-six patients got a diagnosis of a current insomnia using a structured interview for DSM-III-R. Fifty percent of them had at least one additional current Axis I or II diagnosis. Affective disorders were most common as principal psychiatric diagnosis followed by substance use disorders. The general practitioners were poor in recognizing their patients' chronic insomnia complaints and the high percentage of substance abusers among them. The important role of psychopathology in chronic insomnia sufferers was indicated by the high number of patients who displayed prominent personality traits. The predominant personality pattern was characterized by a pattern of internalization of problems combined with an anxious-depressive reaction style. In summary, strong associations between chronic insomnia, mental disorders and psychopathology were confirmed by this investigation.
Adolescent↗
Formation of 7,8-dihydro-8-oxoguanine in the 1,2-dioxetane-induced oxidation of calf thymus DNA: evidence for photosensitized DNA damage by thermally generated triplet ketones in the dark.
Isolated calf thymus DNA was treated with the 1,2-dioxetanes 3-acetoxymethyl-3,4,4-tri-methyl-1,2-dioxetane, 2,3-dimethylbenzofuran dioxetane, 3-hydroxymethyl-3,4,4-trimethyl-1,2-dioxetane (HTMD), 3,3,4,4-tetramethyl-1,2-dioxetane and 3,4,4-trimethyl-1,2-dioxetane (TrMD), which on thermal decomposition generate triplet-excited carbonyl products. To monitor quantitatively the formation of the mutagenic oxidation product 7,8-dihydro-8-oxoguanine (8-oxoGua), a sensitive and selective HPLC electrochemical assay was used after acidic hydrolysis (HF/pyridine) of the dioxetane-treated DNA. High yields of 8-oxoGua (up to ca 4% of the available guanine) were obtained for HTMD and TrMD. Both were investigated in detail with respect to effects of concentration, time and temperature. The oxidative reactivity of 1,2-dioxetanes was compared with several type I (benzophenone and riboflavin) and type II (methylene blue and rose bengal) photooxidants and disodium 1,4-etheno-2,3-benzodioxin-1,4-dipropionate as a chemical source of singlet oxygen. The persistence of 8-oxoGua towards oxidation by HTMD was examined in the reaction with 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodGuo) and with oxidized DNA. It was shown that, indeed, 8-oxoGua is consumed in the oxidized DNA on prolonged exposure to an excess of HTMD. The reaction of 8-oxodGuo with HTMD afforded the two 4R* and 4S* diastereomers of 9-(2-deoxy-beta-D-erythropentofuranosyl)-4, 8-dihydro-4-hydroxy-8-oxoguanine as main oxidation products. Trapping experiments with tert-butanol confirmed that hydroxyl radicals are not involved, whereas the use of the triplet quenchers sodium 9,10-dibromo-anthracene-2-sulfonate and 2,3-diazabicyclo[2.2.1]hept-2-ene established that triplet-excited states are mainly responsible for the observed DNA oxidation through type I action (electron transfer chemistry). The role of singlet oxygen was tested by means of deuterium isotope effects in D2O versus H2O, but no definitive conclusion could be reached in regard to the involvement of 1O2 in these oxidations.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗