Search PubMed⌕ Search

Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 109 records · Page 6Linked to original sources
PubMed2000

[Substance P receptor antagonists--a new antidepressive and anxiolytic mechanism?].

Preclinical investigations suggest that the neuropeptide substance P might be involved in the etiopathology of pain, depression, and anxiety. In a recent study, the substance P receptor antagonist MK-869 showed antidepressant and anxiolytic activity in depressed outpatients which was comparable to a standard SSRI. The MK-869 was well tolerated. Although these findings are promising, further studies are necessary to prove the hypothesis that substance P receptor antagonists represent a new class of antidepressants or anxiolytics. Respective studies are currently underway.

Anti-Anxiety Agents↗
PubMed2000

Ex vivo expansion of CD34+/CD41+ late progenitors from enriched peripheral blood CD34+ cells.

In our experience, patients with neuroblastoma who undergo transplantation with CD34+ cells following high-dose chemotherapy have prolonged delays in platelet recovery. In vitro expansion of megakaryocyte (MK) cells may provide a complementary transplant product able to enhance platelet production in the recipient. We investigated the ability of a combination of various hematopoietic growth factors to generate ex vivo MK progenitors. Immunoselected CD34+ cells from peripheral blood stems cells (PBSCs) were cultured in media with or without serum, supplemented by IL-3, IL-6, IL-11, SCF, TPO, Flt-3 ligand, and MIP-1alpha. In terms of MK phenotypes, we observed a maximal expansion of CD61+, CD41+, and CD42a of 69-, 60-, and 69-fold, respectively, i.e., 8-10 times greater than the expansion of total cell numbers. Whereas the absolute increment of CD34+ cells was slightly elevated (fourfold) we showed increases of 163-, 212-, and 128-fold for CD34+/CD61+, CD34+/CD41+, and CD34+/CD42a+ cells, respectively. We obtained only a modest expansion of CFU-MKs after only 4 days of culture (fourfold) and similar levels of CFU-MKs were observed after 7 days (fivefold). Morphology and immunohistochemistry CD41+ analyses confirmed expansion of a majority of CD41+ immature cells on days 4 and 7, while on day 10 mature cells began to appear. These results show that primarily MK progenitors are expanded after 4 days of culture, whereas MK precursor expansion occurs after 7 days. When we compared the two culture media (with and without serum) we observed that increases of all specific phenotypes of the MK lineage were more elevated in serum-free culture than in medium with serum. This difference was especially marked for CD34+/CD61+ and CD34+/CD41+ (163 vs 42 and 212 vs 36, respectively). We contaminated CD34+ cells with a neuroblastoma cell line and we observed no expansion of malignant cells in our culture conditions (RT-PCR for tyrosine hydroxylase positive at day 4 and negative at day 7). With our combination of hematopoietic growth factors we are able to sufficiently expand ex vivo MK late progenitor cells to be used as complementary transplant products in neuroblastoma patients who undergo transplantation with CD34+ cells. It is possible that these committed MK late progenitors could accelerate short-term platelet recovery in the recipient until more primitive progenitor cells have had time to engraft.

Antigens, CD34↗
PubMed2000

The effect of rivastigmine on sleep in elderly healthy subjects.

Previous research has shown that acetylcholinesterase inhibitors may affect REM sleep, however, results are inconclusive. From the present findings it is concluded that the effects of rivastigmine, a reversible acetycholinesterase inhibitor, on REM sleep are more pronounced in the elderly where we found REM latency to be significantly reduced. This may be explained by better bioavailability and/or by reduced stability of the circadian rhythmicity in elderly individuals. Because rivastigmine is used in the treatment of Alzheimer's disease, further research investigating the relationship between the REM enhancing properties of rivastigmine and cognitive functioning seems promising.

Aged↗
PubMed2000

Granulocyte colony-stimulating factor alone at 20 micrograms/kg vs. 10 micrograms/kg for peripheral blood stem cell mobilization in children.

Mobilization of peripheral blood stem cells (PBSC) by granulocyte colony-stimulating factor (G-CSF), at 10 micrograms/kg/day vs. 20 micrograms/kg/day (in 42 and 29 patients, respectively), was compared in children with solid tumors or leukemias. During mobilization, differences were noted in the peak values of CD34+ cells in peripheral blood (PB) in these two groups (median 28 x 10(6)/L for 10 micrograms/kg/day vs. 61 x 10(6)/L for 20 micrograms/kg/day; p = 0.025). Similar numbers of progenitor cells were harvested for the two concentrations of G-CSF. However, similar CD34+ cell levels in the leukapheresis product were obtained after only the third dose of G-CSF at 20 micrograms/kg/day compared with the fourth dose of G-CSF at 10 micrograms/kg/day (1.7 and 1.2 x 10(6) CD34+ cells/kg/one patient's blood volume processed, respectively). Of note is the impact of diagnosis on PB CD34+ cell levels. We conclude that, in children, mobilization with G-CSF at 20 micrograms/kg/day could minimize the duration of priming but not reduce the number of leukaphereses. Thus, the impact on outcome, clinical practice, bed utilization, and health economics is uncertain.

Adolescent↗
PubMed2000

Autonomous multi-lineage differentiation in vitro of primitive CD34+ cells from patients with chronic myeloid leukemia.

Neoplastic CD34+ cells from chronic myeloid leukemia (CML) patients proliferate in vitro in the absence of serum or defined growth factors due to an autocrine mechanism involving IL-3 and G-CSF (Jiang et al. Proc Natl Acad Sci USA 1999; 96: 12804). Detailed examination of the various cell types produced in such cultures has now demonstrated the rapid, factor-independent, generation of clonogenic progenitors for all lineages (granulocyte-macrophage, megakaryocyte and erythroid) with the additional appearance within 10 days of large numbers of mature granulocytes, macrophages, and megakaryocytes, as well as occasional erythroid cells. Inclusion of flt3-ligand, Steel factor, IL-3, IL-6, and G-CSF +/- erythropoietin (EPO) in the cultures enhanced only slightly the output of mature cells (except for the erythroid population which was much larger when EPO was added). Analogous subpopulations of normal CD34+ cells produced similar numbers and types of cells but, as expected, only when growth factors were added. Thus primitive CD34+ CML cells proliferating autonomously in vitro recapitulate the full spectrum of differentiation responses of normal CD34+ cells stimulated by IL-3 and G-CSF. These findings point to a role of autocrine IL-3 and G-CSF in the similar multi-lineage expansion of differentiating CD34+ CML cells that occurs in vivo.

Antigens, CD34↗
PubMed2000

Two-step immunoablative treatment with autologous peripheral blood CD34(+) cell transplantation in an 8-year-old boy with autoimmune haemolytic anaemia.

Life-threatening haemolysis in children with autoimmune haemolytic anaemia (AIHA) occurs rarely. Many cases of severe autoimmune disease are currently treated with immunosuppressive high-dose chemotherapy and autograft. We report here a case of a child with severe AIHA who did not respond to conventional treatments, but was cured with an autologous peripheral blood CD34(+) cell transplantation. After d 16 post autograft, no further red cell transfusions were required. At 20 months post autograft, haematological complete remission persists.

Anemia, Hemolytic, Autoimmune↗
PubMed2000

Non-linear effects of blood pressure and glycosylated haemoglobin on progression of diabetic nephropathy.

OBJECTIVE: To describe the long-term simultaneous impacts of blood pressure and glycosylated haemoglobin values on the risk of progression of diabetic nephropathy. DESIGN: Prospective, multicentre, 6-year follow-up study. SETTING: One reference centre (university department of internal medicine) and nine general hospitals. SUBJECTS: A total of 601 type 1 diabetic patients on intensive insulin therapy with and without diabetic nephropathy. MAIN OUTCOME MEASURES: Progression of nephropathy was defined as change for the worse within five stages of nephropathy by at least one of these stages during the study period. By the use of logistic regression, the relationship between metabolic and blood pressure control and the risk of nephropathy progression was quantified. RESULTS: The main determinants of nephropathy progression were glycosylated haemoglobin and blood pressure, which were both non-linearly associated with the risk of progression. No significant threshold levels for any of the predictors of progression were identified. CONCLUSIONS: The results of this study underline the importance of optimizing metabolic and blood pressure control to arrest the progression of diabetic nephropathy without the evidence for a clinically relevant threshold effect.

Adult↗
PubMed2000

Effects of on-demand beta2-agonist inhalation in moderate-to-severe asthma. A randomized controlled trial.

BACKGROUND: The appropriate use of short-acting beta2-agonist inhalation in asthma has been the subject of controversy in recent years. Limited information is available for the group of moderate to severe asthmatics with high intake of bronchodilator inhalants and continuous anti-inflammatory protection. OBJECTIVE: To investigate the effects of beta2-agonist reduction in marked asthma treated with multiple asthma medications. DESIGN: Randomized, controlled single-blind, cross-over trial. SETTING: Outpatient clinic at a university medical centre. SUBJECTS: A total of 80 adult patients with moderate-to-severe asthma. INTERVENTIONS: In a 1-year study patients were assigned to on-demand vs. regular beta2-agonist inhalation treatment. MAIN OUTCOME MEASURES: Asthmatic episodes (primary outcome), symptoms, peak expiratory flow rates (PEF) and drug use were recorded daily. Bronchodilator and airway responsiveness, lung function indices and quality of life were assessed during five clinic visits. Also, practicability of beta2-agonist tapering in multimedicated asthmatics was analysed. RESULTS: More than 80% of moderate-to-severe asthmatics were able to reduce their beta2-agonist intake by >/=50%. Puffs per day of active therapy decreased from 7.9 in regular to 3.3 in on-demand treated patients (P = 0.0001). The type of beta2-agonist used (salbutamol/fenoterol) had no significant impact on the study findings. Almost all parameters of control of asthma improved during the on-demand treatment period. CONCLUSION: On-demand inhalation of short-acting beta2-agonists in moderate-to-severe asthma is safe, and even in severe asthma a reduction from regular to on-demand beta2-agonist inhalation is possible, with improved asthma control.

Acute Disease↗
PubMed2000

Prognosis of persons with type 1 diabetes on intensified insulin therapy in relation to nephropathy.

OBJECTIVE: To study the prognosis of persons with type 1 diabetes in relation to the degree of nephropathy at initiation of intensified insulin therapy. DESIGN: Ten years follow-up of a cohort of 3674 patients who had participated in a 5-day group treatment and teaching programme for intensification of insulin therapy between September 1978 and December 1994. SETTING: Ten diabetes centres in Germany. SUBJECTS: A total of 3674 patients (insulin treatment before age 31), age at baseline 27 +/- 10 years, with a diabetes duration of 11 +/- 9 years. Patients were divided into three groups according to baseline renal parameters (group I, normal proteinuria, n = 1829; group II, microproteinuria, n = 1257; group III, at least macroproteinuria, n = 367). MAIN OUTCOME MEASURES: End-stage diabetic complications (blindness, amputations, renal replacement therapy, standardized mortality ratios (SMR) and causes of death. RESULTS: Outcome measures were documented for 97% of patients; 251 (7%) had died. During follow-up, 1% of patients in group I, 4% in group II and 47% in group III had at least one end-stage diabetic complication. SMR for men: nephropathy group I, 2.2 (95% CI = 1.5-3); group II, 3.2 (2.3-4.3); group III, 11.5 (8.8-14.7). SMR for women: group I, 2.5 (1.5-3.8); group II, 3.5 (2.2-5.3); group III, 27 (19.8-35.9). Causes of death for men and women combined: group I (total 58 deaths)--cardiovascular, 21 (36%); hypoglycaemia, 1; ketoacidosis, 3; violent deaths, 17 (29%); others, 16; group II (66 deaths)--cardiovascular, 25 (38%); hypoglycaemia, 2; ketoacidosis, 2; violent deaths, 14 (21%); others, 23; group III (114 deaths)--cardiovascular, 68 (60%); hypoglycaemia, 2; ketoacidosis, 5; infections, 15 (13%); violent deaths, 5 (4%); others, 19. CONCLUSIONS: Patients with microproteinuria have only a slightly worse prognosis than patients with normal proteinuria during the first 10 years after initiation of intensified insulin therapy. Excess mortality amongst patients who started intensified insulin therapy is mainly due to those with manifest clinical nephropathy.

Adult↗
PubMed2000

Molecular cloning and characterization of murine and human N-acetylglucosamine kinase.

N-Acetylglucosamine is produced by the endogenous degradation of glycoconjugates and by the degradation of dietary glycoconjugates by glycosidases. It enters the pathways of aminosugar metabolism by the action of N-acetylglucosamine kinase. In this study we report the isolation and characterization of a cDNA clone encoding the murine enzyme. An open reading frame of 1029 base pairs encodes 343 amino acids with a predicted molecular mass of 37.3 kDa. The deduced amino-acid sequence contains matches of the sequences of eight peptides derived from tryptic cleavage of rat N-acetylglucosamine kinase. The recombinant murine enzyme was functionally expressed in Escherichia coli BL21 cells, where it displays N-acetylglucosamine kinase activity as well as N-acetylmannosamine kinase activity. The complete cDNA sequence of human N-acetylglucosamine kinase was derived from the nucleotide sequences of several expressed sequence tags. An open reading frame of 1032 base pairs encodes 344 amino acids and a protein with a predicted molecular mass of 37.4 kDa. Similarities between human and murine N-acetylglucosamine kinase were 86.6% on the nucleotide level and 91.6% on the amino-acid level. Amino-acid sequences of murine and human N-acetylglucosamine kinase show sequence similarities to other sugar kinases, and all five sequence motifs necessary for the binding of ATP by sugar kinases are present. Tissue distribution of murine N-acetylglucosamine kinase revealed an ubiquitous occurrence of the enzyme and a very high expression in testis. The size of the murine mRNA was 1.35 kb in all tissues investigated, with the exception of testis, where it was 1.45 kb mRNA of the murine enzyme was continuously expressed during mouse development. mRNA of the human enzyme was expressed in all investigated human tissues, as well as in cancer cell lines. In both the tissues and the cancer cell lines, the human mRNA was 1.35 kb in size.

Amino Acid Sequence↗
PubMed2000

Expression of the gene and processed pseudogenes encoding the human and rabbit translationally controlled tumour protein (TCTP).

In humans and rabbits, the TPT1 gene encoding the translationally controlled tumour protein TCTP generates two mRNAs (TCTP mRNA1 and TCTP mRNA2) which differ in the length of their 3' untranslated regions. The distribution of these mRNAs was investigated in 10 rabbit and 50 human tissues. They were transcribed in all tissues investigated, but differed considerably in their quantity and ratio of expression. This indicates an extensive transcriptional control and involvement of tissue-specific factors. In the rabbit genome numerous processed, intronless pseudogenes were detected. Four, corresponding to both types of mRNAs, were sequenced and analysed in detail; all displayed only few mutations and were either preserved completely in the original amino acid sequence of the intron containing gene, or contained only minor mutations in the coding region which did not interrupt the open reading frame. In the mRNA population of rabbit reticulocytes two additional TCTP RNAs of the TCTP mRNA2 type were detected, which have the characteristics of pseudogene transcripts. Pseudogene transcription was supported further by CAT reporter gene assays showing substantial promoter activity of 5'-flanking regions of two TPT1 pseudogenes.

Animals↗
PubMed2000

Evaluation of a holistic treatment and teaching programme for patients with Type 1 diabetes who failed to achieve their therapeutic goals under intensified insulin therapy.

AIMS: To evaluate a treatment and teaching programme including psychosocial modules for patients with Type 1 diabetes mellitus on intensified insulin therapy who failed to achieve their treatment goals despite participation in standard programmes. METHODS: The 5-day inpatient programme comprises small groups of 4-6 patients, focusing on individual needs and problems. Beyond the teaching lessons (most topics are deliberately chosen by the patients), the programme provides intensive group discussions and offers individual counselling concerning motivational aspects, psychosocial problems and coping strategies. Of the first consecutive 83 participants, 76 were re-examined after 17.5 +/- 5.5 months (range 9-31 months). RESULTS: At follow-up, HbA1c was not improved compared to baseline (8.0 +/- 1.3% vs. 8.1 +/- 1.5%). However, the incidence of severe hypoglycaemia per patient/year (glucose i.v., glucagon injection) was substantially decreased: 0.62 +/- 1.5 episodes at baseline compared to 0.16 +/- 0.9 at follow-up (P < 0.001). Twenty-six per cent of the patients at baseline, and 4% at re-examination had experienced at least one episode of severe hypoglycaemia during the preceding year (P < 0.001). Sick leave days per patient/year decreased from 17.0 +/- 38.5-7.7 +/- 13.6 days (P < 0.05). Patients improved their perceptions of self-efficacy, their relationship to doctors and felt less externally controlled (P < 0.001). The majority of patients perceived an improved competence regarding diet (80.6%) and adaptation of insulin dosage (82.4%), an improved knowledge (82.2%), and a renewed motivation for the treatment (84.5%). Treatment success was significantly associated with baseline HbA1c, stability of motivation, frequency of blood glucose self-monitoring, control beliefs and change in subsequent outpatient care. CONCLUSIONS: The programme improved glycaemic control mainly as a result of a substantial reduction in the incidence of severe hypoglycaemia. Patients with persistent poor glycaemic control may benefit from structured follow-up care focusing on motivational aspects of self-management and psychosocial support.

Adaptation, Psychological↗
PubMed2000

Predictors of mortality and end-stage diabetic complications in patients with Type 1 diabetes mellitus on intensified insulin therapy.

AIMS: To assess predictors of mortality and end-stage diabetic complications in patients with Type 1 diabetes mellitus on intensified insulin therapy. METHODS: A cohort of 3,674 patients (insulin treatment before age 31) who had participated in a 5-day in-patient group treatment and teaching programme for intensification of insulin therapy between 9/1978 and 12/1994 were reassessed after 10 +/- 3 (mean +/- SD) years. RESULTS: Vital status and data on blindness, amputations, and renal replacement therapy were documented for 97% patients; 7% patients had died, 1.3% had become blind, 2% had amputations and 4.6% started renal replacement therapy. Using the Cox proportional hazards model, the following risk factors of mortality as assessed at baseline were identified: nephropathy (at least macroproteinuria), hazard ratio 3.8 (95% confidence interval 2.6-5.6); smoking, 1.9 (1.4-2.6); diabetes duration, 1.5 (1.2-1.8) for a difference of 10 years; serum cholesterol, 1.1 (1.0-1.2) for a difference of 1 mmol/l; lower social status, 1.4 (1.1-1.8) for a difference of 1 out of 3 levels; age, 1.3 (1.1-1.6) for a difference of 10 years; male sex, 1.4 (1.1-1.9); systolic blood pressure, 1.1 (1-1.2) for a difference of 10 mmHg. For the combined endpoint - blindness or amputations or renal replacement therapy - predictors were: nephropathy, foot complications, HbA1c, smoking, cholesterol, systolic blood pressure, retinopathy, hypertension, and social status. CONCLUSION: In Type 1 diabetic patients who start intensified insulin therapy, nephropathy remains the strongest predictor of mortality and end-stage complications. Glycosylated haemoglobin is a risk factor of end-stage complications but not of mortality. Conventional risk factors comparable to the general population, particularly smoking become operative as predictors of both mortality and end-stage complications.

Adult↗
PubMed2000

Evidence-based patient information in diabetes.

Patient education in diabetes has been successful in training and motivating patients to assume a more active and independent role in monitoring and treating their disease resulting in an improvement of patient-orientated outcomes. Traditionally, diabetes education has mainly aimed at increasing patient compliance to physician-defined therapeutic goals and treatment strategies. To strengthen their rights and autonomy, patients need to become more involved in medical decision making with respect to their individual therapeutic goals, such as HbA1c and blood pressure, body weight, etc., as well as choosing whether they pursue these goals. The importance of patient participatation is particularly relevant to Type 2 diabetes. Even perfect, long-term therapeutic co-operation will not eliminate diabetic complications, only reduce the risk of developing them. The benefits, lack of benefits and unwanted effects of various interventions need to be communicated to the patient in an unbiased manner, so that he/she can make an informed choice with regard to different therapeutic goals and strategies. In diabetes, ways of presenting patients with unbiased information to enable them to make such informed decisions are not yet available. We present ways of how this might be achieved using data provided by the UKPDS. The concept of patient participation in medical decision making represents a fundamental challenge for the future development of diabetes care.

Blood Pressure↗
PubMed2000

Carcinoid heart disease in association with a primary ovarian carcinoid tumor: diagnostic role of echocardiography.

We describe a patient with carcinoid heart disease secondary to a primary ovarian carcinoid tumor who initially presented with unexplained right-sided heart failure. The patient did not exhibit any of the typical clinical manifestations of the carcinoid syndrome. Echocardiography demonstrated typical features of carcinoid heart disease and played an important role in the detection and management of a condition that was previously unrecognized.

Aged↗
PubMed2000

Chlamydia pneumoniae DNA in non-coronary atherosclerotic plaques and circulating leukocytes.

Earlier studies have associated atherosclerosis with Chlamydia pneumoniae infection. C. pneumoniae may circulate via monocytes and migrate into plaques by leukocyte infiltration; however, detection is difficult. We developed a novel polymerase chain reaction (PCR) method to test the hypothesis that C. pneumoniae DNA in circulating leukocytes is correlated with C. pneumoniae DNA in plaque material and that C. pneumoniae copy number is associated with disease severity. We obtained plaques from 130 patients who underwent surgery for carotid stenosis, aneurysm, or peripheral vascular disease. From 60 patients and 51 normal control subjects we also obtained circulating leukocytes. The C. pneumoniae 16 S rRNA gene was amplified with a highly specific quantitative PCR protocol relying on the TaqMan technology. Immunohistochemistry was performed with antibody against the C. pneumoniae outer membrane protein. C. pneumoniae DNA was present in 25% of atherosclerotic plaques and 20% of circulating leukocytes from patients. The copy number was not correlated with disease severity. C. pneumoniae DNA was more common in younger patients and smokers. C. pneumoniae antibody titers, C-reactive protein, fibrinogen, leukocyte count, cholesterol, and diabetes were not associated with C. pneumoniae DNA. Although immunostaining of plaque and PCR results were highly correlated, we found no relationship between C. pneumoniae DNA in plaques and that in circulating leukocytes. Finally, 13% of normal control subjects had positive leukocytes; however, their copy number was significantly lower than that of the patients. C. pneumoniae DNA is frequent in atherosclerotic plaques and is correlated with positive immunohistochemistry. C. pneumoniae DNA may also be found in circulating leukocytes; however, infected leukocytes and plaques do not coincide. Serology is unreliable in predicting C. pneumoniae DNA. Smoking increases the risk of harboring C. pneumoniae DNA. Our results do not suggest that either test for antibodies or C. pneumoniae DNA from leukocytes in blood is of value in predicting infected plaques.

Aged↗
PubMed2000

Elevated serum free fatty acid concentrations inhibit T lymphocyte signaling.

Unbound cis-unsaturated free (i.e., nonesterified) fatty acids (FFA) inhibit T lymphocyte activation in vitro and therefore may exert immunosuppressive effects. However, in blood serum the major proportion of FFA is tightly bound to albumin, whereas unbound FFA are hardly detectable. Since serum FFA elevation occurs under pathological conditions like insulin resistance or cancer, which are often associated with a disturbed immune response, we addressed the question of whether increased serum FFA concentrations could affect T lymphocyte activation under in vivo conditions. Our studies revealed that 1) addition of pure long-chain cis-unsaturated FFA in the absence of albumin inhibited calcium response in cultured Jurkat T cells. 2) In healthy volunteers, serum FFA elevation by a lipid/heparin infusion, including predominantly unsaturated fatty acids, decreased calcium response of cultured T cells in contrast to studies without heparin. 3) Most notably, stepwise increasing serum FFA by lipid/heparin infusion also inhibited calcium response of simultaneously isolated autologous peripheral blood T lymphocytes as well as their CD4(+) and CD8(+) subsets. In conclusion, our data emphasize that serum FFA elevation is able to exert immunosuppressive effects in vivo.

Adult↗