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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 379 records · Page 21Linked to original sources
PubMed1994

5-Fluorouracil, folinic acid, etoposide and cisplatin chemotherapy for locally advanced or metastatic carcinoma of the oesophagus.

38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.

Adenocarcinoma↗
PubMed1994

Carba analogues of triglycerides--isosteric mimics for natural lipids. Novel substrates for the determination of regio- and enantioselectivities displayed by lipases.

The novel carba analogues 1a,b and 2 were synthesized and demonstrated to be isosteric identical mimics for natural triglycerides. They can be used for the system independent determination of regio- and enantioselectivities displayed by lipases. They are, moreover, attractive starting materials for novel carba analogues of phospholipids, PAF analogues and PAF antagonists.

Animals↗
PubMed1994

Influence of biperiden and bornaprine on sleep in healthy subjects.

Biperiden, 4 mg, an anticholinergic drug that is relatively selective for the M1 receptor subtype, and bornaprine, 4 mg, a nonselective M1 and M2 antagonist, were administered orally in a randomized, double-blind design to twelve healthy volunteers to investigate the effect on polysomnographically recorded sleep. Both drugs suppressed rapid eye movement (REM) sleep as reflected by an increase of REM latency and a decrease in the percentage of REM sleep period time with the effects of biperiden being more pronounced. No significant effect on slow wave sleep was observed. The results of this study support the hypothesis that both the M1 and the M2 receptor subtype are involved in the regulation of REM sleep in humans.

Adult↗
PubMed1994

[Depression and sleep--the status of current research].

Abnormalities of REM sleep, i.e. shortening of REM latency, lengthening of the duration of the first REM period and heightening of REM density, which are frequently observed in patients with a Major Depressive Disorder (MDD), have attracted considerable interest. Initial hopes that these aberrant patterns of sleep constitute specific markers for the primary/endogenous subtype of depression have not been fulfilled. The specificity of REM sleep disinhibition for depression in comparison to other psychopathological groups is also challenged. Demographic variables like age and sex exert strong influences on sleep physiology and must be controlled when searching for specific markers of depressed sleep. It is still an open question whether abnormalities of sleep are state-markers or trait-markers of depression. Beyond baseline studies, the cholinergic REM induction test (CRIT) indicated a heightened responsitivity of the REM sleep system to cholinergic challenge in depression compared with healthy controls and other psychopathological groups, with the exception of schizophrenia. A special role for REM sleep in depression is supported by the well known REM sleep suppressing effect of most antidepressants. The antidepressant effect of selective REM deprivation by awakenings stresses the importance of mechanisms involved in REM sleep regulation for the understanding of the pathophysiology of depressive disorders. The positive effect of total sleep deprivation on depressive mood which can be reversed by daytime naps, furthermore emphasizes relationships between sleep and depression. Experimental evidence as described above instigated several theories like the REM deprivation hypothesis, the 2-process model and the reciprocal interaction model of nonREM-REM sleep regulation to explain the deviant sleep pattern of depression. The different models will be discussed with reference to empirical data gathered in the field.

Animals↗
PubMed1994

[Contraception in patients with type I diabetes: a survey of 808 women of reproductive age].

UNLABELLED: In-depth advice about contraception is important for type I diabetic women since special medical aspects have to be considered and because pregnancy should be planned. The actual contraceptive practice in diabetic women living in Germany had not been investigated before. METHODS: In December 1992 type I diabetic women of 16 to 46 yrs of age who had consecutively participated in a diabetic treatment and teaching programme (n = 1028) were mailed a multiple-choice questionnaire about reproductive and contraceptive issues. 409 non-diabetic women were also questioned and served as a control group. RESULTS: 808 diabetic women (age 32[7] yrs, duration of diabetes 14[8] yrs) returned the questionnaire. The percentage of women using a method of contraception was comparable between diabetic and control women (76 vs. 72%). Of these, fewer diabetic women used oral contraceptives (OC) (33 vs. 57%). The OC-using diabetic women were younger than those using other methods (27[5] vs. 33[7] yrs), however 63% had at least one of the contraindications for OC-use (smoking, hypertension, proteinuria, retinopathy, poor metabolic control) and 18% were using high-dose preparations. More diabetic than control women used IUDs (19 vs. 12%) and more diabetic women were sterilised (19 vs. 9%). Compared to controls diabetic women had had sterilisation at a younger age (31[5] vs. 36[4] yrs) and more sterilised women were childless (29 vs. 14%). Methods of lower efficacy (condom, diaphragma, spermatocides) were used by 26% of diabetic women (controls 20%), p < 0.05. Nearly half of the diabetic women had received contraceptive advice exclusively by gynaecologists. 22% of all pregnancies were unplanned (controls 17%); 0 > 0.05). CONCLUSION: More diabetic women should use methods of contraception with high efficacy. However, when prescribing OCs more attention must be payed to special contraindications. Sterilisation should be recommended more cautiously to diabetic women without advanced diabetic complications. Contraceptive advice to diabetic women must be given by gynaecologists and diabetologists.

Adolescent↗
PubMed1994

The effects of cooperative and individualistic reward on intrinsic motivation.

The effects of cooperative versus individualistic reward on students' intrinsic motivation were investigated. The controlling aspects of extrinsic reward may be heightened or produce greater ego threat in the individualistic situation when compared with a group situation. We predicted that students in the cooperative social situation would show higher levels of intrinsic motivation. Fifth-grade students from existing cooperative groups were assigned randomly to receive a tangible reward based on either cooperative or individualistic achievement for completing pattern block designs. Cooperation affected intrinsic motivation positively. Students in the cooperative dyad solved the block designs more quickly, interacted positively, and viewed the task as easier than did those in the individualistic situation, and they reported that their peers were helpful. There was little evidence that the controlling functions of reward or ego-threat were factors in producing the outcome. Some evidence supporting the importance of the social nature of cooperation was provided.

Child↗
PubMed1994

Aminothiols linked to quinoline and acridine chromophores efficiently decrease 7,8-dihydro-8-oxo-2'-deoxyguanosine formation in gamma-irradiated DNA.

In a search for more active radioprotective compounds, we have prepared and examined a series of model molecules in which the radioprotective beta-aminothiol unit (free or derivatized as acetate or phosphorothioate) is tethered to the DNA-binding chromophores quinoline and acridine through links of variable length. The modifying activity of these 'hybrid' molecules was estimated by measuring the formation of 8-oxo-2'-deoxyguanosine (8-oxodGuo) in double-strand DNA upon exposure to gamma-rays in oxygen-free solution in the presence of the drugs. We show that all hybrid molecules protect the guanine moiety from oxidation more efficiently than the parent beta-aminothiol units. The degree of protection is the highest for the molecules in which the thiol is linked to the strong binding intercalator acridine through a long polyaminochain.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

The clinical significance of insulin resistance in the treatment of hypertension.

A strong association between arterial hypertension and Type 2 diabetes mellitus has been known for more than 70 years. However, there are many unanswered questions with regard to the hypothesis of a causal relationship between insulin resistance/hyperinsulinaemia and arterial hypertension. At present, there is no hard evidence for a close (causal) linkage between insulin resistance (or hyperinculinaemia) and arterial hypertension. Currently available antihypertensive drugs in prudent and effective dosages do not result in a deterioration of insulin sensitivity, or in the development of insulin resistance, or an increased incidence of Type 2 diabetes mellitus.

Antihypertensive Agents↗
PubMed1994

Enhancement by tumor necrosis factor-alpha of Fc alpha receptor expression and IgA-mediated superoxide generation and killing of Pseudomonas aeruginosa by polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMNL) in bronchoalveolar lavage (BAL) fluid of cystic fibrosis patients express increased levels of receptor for the Fc portion of IgA (Fc alpha R), similar to those found on PMNL stimulated with FMLP in vitro. Since tumor necrosis factor-alpha (TNF alpha) is an activator of PMNL and is found at inflammatory sites, its effects on Fc alpha R expression and IgA-mediated PMNL functions were investigated. Exposure of PMNL to TNF alpha increased surface expression of Fc alpha R 2- to 3-fold, increased superoxide production in response to aggregated IgA 5-fold, and increased phagocytosis of IgA aggregates 3- to 4-fold. Interleukin-8 did not increase Fc alpha R expression and did not enhance IgA-mediated superoxide generation. IgA-dependent PMNL killing of Pseudomonas aeruginosa was enhanced when PMNL were pretreated with TNF alpha. Thus, interactions between phagocytic host defense mechanisms and mucosal IgA may be enhanced by TNF alpha in the inflammatory milieu of the cystic fibrosis lung.

Adolescent↗
PubMed1994

Use of G-CSF alone to mobilize peripheral blood stem cells for collection from children.

We report the data of 19 children with neuroblastoma (NB) or Ewing's sarcoma (EW) who had peripheral blood stem cells (PBSCs) harvested after mobilization by: (1) cyclophosphamide (CY) + etoposide + G-CSF, (2) CY + GM-CSF, or (3) G-CSF alone. There were no consistent differences in the number of PBSCs collected following these three different mobilization regimens as assessed by CFU-GM. 17 patients were reinfused with PBSCs after myeloablative therapy and had successful haemopoietic recovery. These results show that in children with solid tumours such as NB or EW a sufficient number of PBSCs can be collected after G-CSF alone, and that PBSCs collected following stimulation by G-CSF alone are as effective in reconstituting haemopoiesis as those collected after mobilizing chemotherapy + HGFs.

Child↗
PubMed1994

Predictors of glycaemic control in type 1 diabetic patients after participation in an intensified treatment and teaching programme.

The aim of the study was to identify predictors of long-term glycaemic control in Type 1 diabetic patients after participation in an intensified insulin treatment and teaching programme. The study population consisted of 697 Type 1 diabetic patients (mean age 26 +/- 7 (SD) years, duration of diabetes 8 +/- 7 years) who participated in the same structured intensified insulin treatment and teaching programme in 10 hospitals and who were re-examined after 1, 2, and 3 years. Multiple and logistic regression analyses were performed including a set of demographic, disease-related, social, and psychosocial variables as potential predictors. As dependent variables the average HbA1 values during the 3-year follow-up period and a composite variable (average HbA1 values/frequency of severe hypoglycaemia)--dividing patients into three groups with good, moderate or poor metabolic control--were considered. Regression analysis of average HbA1 values revealed significance (p < 0.05) for seven independent predictors in descending order: smoking, age at onset of diabetes, frequency of home blood glucose monitoring, socioeconomic status, diabetes-related knowledge, perceived coping abilities, and sex (R2 (percentage of variation explained by the model) = 17%). In a second regression model, HbA1 values before the intervention programme were added to the model and achieved the highest standardized regression coefficient (0.38), increasing R2 to 29%. In the logistic regression models considering both HbA1 and severe hypoglycaemia as a composite dependent variable, diabetes-related knowledge, HbA1 values before the intervention, smoking, perceived coping abilities, age at onset of diabetes, and C-peptide levels were the strongest predictors of glycaemic control. In conclusion, the relationship between demographic, disease-related, psychosocial, and social variables and metabolic control is complex. Therefore, simplistic concepts of linear causality should be abandoned. In addition to HbA1 values before the intervention, smoking, diabetes-related knowledge, home blood glucose monitoring, age at onset of diabetes, perceived coping abilities and C-peptide levels were the most significant and consistent predictors of glycaemic control.

Adolescent↗
PubMed1994

Prevalence of insomnia in elderly general practice attenders and the current treatment modalities.

This study aimed to assess the prevalence and treatment modalities of elderly practice attenders. A total of 330 patients aged over 65 years were investigated with a questionnaire in general practice. To assess insomnia, operationalized diagnostic criteria according to DSM-III-R were applied. Twenty-three percent of the elderly patients suffered from severe, 17% from moderate and 17% from mild insomnia. More than 80% of the patients reported suffering from insomnia for 1-5 years or longer, which indicates a chronic course. Elderly patients showed unrealistic expectations concerning duration of sleep and spend more time in bed than they realistically can expect to sleep. More than half of the elderly patients reported habitual daytime napping. Sleep-disturbed elderly patients did not differ significantly from good sleepers in their habit of taking daytime naps, but even when taking daytime naps, good sleepers slept significantly longer than the sleep-disturbed patients. A significant association was found between insomnia and mental disorders, i.e., depression and organic brain syndrome according to the diagnosis of the general physician. In about half of the cases the primary care physician was not aware that the elderly patient suffered from severe insomnia. More than half of the elderly severe insomniacs took prescribed hypnotics habitually, mainly benzodiazepines.

Aged↗
PubMed1994

Psychosocial adjustment in long-term survivors of childhood medulloblastoma and ependymoma treated with craniospinal irradiation.

Improved prognosis for pediatric brain tumors has stimulated research into the quality of life of survivors. To assess cognitive function and psychosocial and family adjustment among this population, 18 long-term survivors of childhood medulloblastoma or posterior fossa ependymoma treated with surgical resection and craniospinal irradiation were interviewed and administered achievement tests and psychosocial questionnaires. A majority of parents reported significant difficulty caring for their child with a brain tumor, but no significant adverse effects upon the family. Academic achievement was significantly impaired in 12/18 subjects. Psychosocial adjustment was normal in 10/18 subjects. Although specific treatment variables (radiation dosage, chemotherapy, etc.) were not significantly related to these two outcome measures, impaired academic achievement was correlated with young age at diagnosis (p < 0.05) and impaired psychosocial adjustment was correlated with greater time since diagnosis (p < 0.05). Overall quality of life reported by these individuals appears to be acceptable but neuropsychological and psychosocial examination is clearly indicated as part of the follow-up program.

Achievement↗
PubMed1994

Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation.

To determine the extent of airway infection and inflammation in adolescents and adults with cystic fibrosis (CF) who have mild lung disease and are without symptoms of active infection, we performed bronchoalveolar lavage (BAL) on 18 CF patients > or = 12 yr of age who were stable, appeared clinically well, and had mean (+/- SEM) FEV1 of 79 +/- 4% of predicted. We quantitated the bacteria, inflammatory cells, immunoglobulins, and mediators of inflammatory tissue damage in the epithelial lining fluid (ELF) of these patients and in 23 healthy control subjects. All CF patients were found to be infected with Pseudomonas aeruginosa, Staphylococcus aureus, and/or Haemophilus influenzae; no organisms were isolated from the control subjects. The mean number of cells in the ELF was 14 times greater in the CF patients than in the control subjects. Neutrophils constituted 57% of the recovered cells in the CF patients versus 3% in the control subjects, and their concentration was 380 times greater in the CF patients versus the control subjects. IgG, IgA, and IgM were 2.5 to 6 times greater in CF ELF versus that of control subjects. Abundant active elastase was present in the ELF of the CF patients (2.3 +/- 0.9 microM) despite threefold elevated levels of alpha 1-protease inhibitor (alpha 1-PI). No active elastase was detectable in the control subjects. alpha 1-PI was functional in CF as demonstrated by elevated elastase:alpha 1-PI complex (0.045 microM in CF versus 0.002 microM in control subjects). This active elastase caused proteolytic destruction of surface complement receptors on airway neutrophils in situ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Internalization of type 1 complement receptors and de novo multivesicular body formation during chemoattractant-induced endocytosis in human neutrophils.

Upon activation of human neutrophils by chemoattractants, functionally important proteins are rapidly transported from intracellular granules and storage vesicles to the plasma membrane. This is accompanied by a marked increase in the rate of endocytosis and by ligand-independent internalization of type 1 complement receptors (CR1). To define the pathway of endocytosis, we used gold-conjugated BSA in a pulse-chase protocol. This tracer was initially internalized into small endocytic vesicles which rapidly traversed the cytoplasm and coalesced to form large, conspicuous multivesicular bodies. Within 5 min after addition of the chemoattractant, multivesicular bodies contained > 60% of the cell-associated BSA-gold. CR1 colocalized with the endocytic tracer in both the early endosomes and multivesicular bodies. In unstimulated cells, there was much less uptake of BSA-gold and multivesicular bodies were rarely seen. Using the acidotropic amine, DAMP, and anti-DNP antibodies, we found that the multivesicular bodies were acidified but the early endosomes did not concentrate DAMP. Neither the early endosomes nor the multivesicular bodies initially contained the lysosomal membrane antigens hLAMP 1 or 2, but hLAMP-positive structures subsequently joined the multivesicular bodies. The rapid activation of the endocytic pathway upon stimulation of neutrophils allowed us to visualize the de novo formation and maturation of multivesicular bodies. Our observations suggest that vesicles containing ion pumps and acid hydrolases fuse with multivesicular bodies, giving them characteristics of lysosomes, and that these are the probable sites of degradation of CR1. The observations do not support models which would require transport of CR1 from multivesicular bodies to defined, pre-existing lysosomes for degradation.

Adamantane↗
PubMed1994

Tissue-specific Fc gamma and complement receptor expression by alveolar macrophages determines relative importance of IgG and complement in promoting phagocytosis of Pseudomonas aeruginosa.

Because the expression of IgG Fc receptors and complement receptors on macrophages may vary in a tissue-specific manner, we used monoclonal antibodies and flow cytometry to define the expression and function of opsonin receptors on fresh normal and cystic fibrosis (CF) bronchoalveolar lavage (BAL) macrophages. Using flow cytometry to separately analyze individual types of cells, we then determined the relative contributions of IgG and complement to phagocytosis of Pseudomonas aeruginosa by fresh BAL cells, avoiding alterations in receptor expression due to in vitro purification or culturing techniques. Neither normal nor CF BAL macrophages express appreciable amounts of the complement receptors CR1, CR2, or CR3. These results were confirmed by immunohistochemical staining of fixed lung sections. BAL macrophages express a high-affinity IgG receptor, Fc gamma RI, that is not found on neutrophils (PMN). In contrast, chemoattractant-stimulated blood PMN express large amounts of CR1 and CR3 but do not express Fc gamma RI. These results correlate with phagocytosis assays, which show that phagocytosis by macrophages is enhanced by relatively low concentrations of IgG but that the addition of complement does not further increase their phagocytosis. In contrast, low concentrations of IgG alone do not promote phagocytosis by PMN, whereas addition of complement markedly enhances phagocytosis by PMN. These results may explain the previously reported sensitivity of macrophages rather than PMN to the "blocking" effects of anti-Pseudomonas antibodies from CF patients, and emphasize the pathologic significance of interference with IgG and complement mediated opsonization in the lung in CF.

Adolescent↗
PubMed1994

Exercise echocardiographic correlates of transient dilatation of the left ventricular cavity on exercise thallium-201 SPECT imaging.

Transient dilatation of the left ventricular cavity on exercise thallium perfusion imaging is recognized as a marker of significant coronary disease, but the mechanisms that produce this finding are not fully understood. We studied 32 patients who underwent exercise thallium imaging and exercise echocardiography to determine the changes in left ventricular cavity size that underlie transient dilatation. Left ventricular area from the apical four-chamber view was used to approximate left ventricular cavity size. There were 24 patients who did not have transient dilatation (group 1) and 8 patients who did have transient dilatation (group 2) on thallium imaging. Systolic area decreased from rest to exercise in group 1 patients but not in group 2 patients. There was no significant change in diastolic area from rest to exercise in either group 1 or group 2 patients. Thus, exercise-induced systolic dysfunction, manifested as a failure to decrease left ventricular systolic cavity size in exercise, may be an important mechanism in producing scintigraphic transient dilatation.

Echocardiography↗