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K Baum

Publications and source records attributed to K Baum.

At least 19 recordsLinked to original sources

Conditional and specific NF-kappaB blockade protects pancreatic beta cells from diabetogenic agents.

Type 1 diabetes is characterized by the infiltration of inflammatory cells into pancreatic islets of Langerhans, followed by the selective and progressive destruction of insulin-secreting beta cells. Islet-infiltrating leukocytes secrete cytokines such as IL-1beta and IFN-gamma, which contribute to beta cell death. In vitro evidence suggests that cytokine-induced activation of the transcription factor NF-kappaB is an important component of the signal triggering beta cell apoptosis. To study the in vivo role of NF-kappaB in beta cell death, we generated a transgenic mouse line expressing a degradation-resistant NF-kappaB protein inhibitor (DeltaNIkappaBalpha), acting specifically in beta cells, in an inducible and reversible manner, by using the tet-on regulation system. In vitro, islets expressing the DeltaNIkappaBalpha protein were resistant to the deleterious effects of IL-1beta and IFN-gamma, as assessed by reduced NO production and beta-cell apoptosis. This effect was even more striking in vivo, where nearly complete protection against multiple low-dose streptozocin-induced diabetes was observed, with reduced intraislet lymphocytic infiltration. Our results show in vivo that beta cell-specific activation of NF-kappaB is a key event in the progressive loss of beta cells in diabetes. Inhibition of this process could be a potential effective strategy for beta-cell protection.

Active Transport, Cell Nucleus↗

[Normalization of the Brief Repeatable Battery of Neuropsychological tests (BRB-N) for German-speaking regions. Application in relapsing-remitting and secondary progressive multiple sclerosis patients].

The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) is a neuropsychological screening battery, often applied in multiple sclerosis (MS) patients. It is almost exclusively administered in trials and not in the daily practice routine because of the lack of normative values. Using a stepwise linear regression analysis, the dependence of test results on age, gender, and education of 241 healthy control subjects was investigated. Z-values of -1.68 or less were considered pathological. Based on the normative values, the proportions of cognitively impaired patients with relapsing-remitting MS (RRMS, n=43) and secondary progressive MS patients (SPMS, n=60) were calculated. The regression model explained 2.7-25.0% of the variance of test performances. Cognitive impairment occurred in 38% and in 47% of the RRMS and the SPMS groups, respectively. In both groups attention and concentration impairment was prominent, while in the SPMS group memory was also frequently affected. The proportion of cognitively impaired MS patients reflected the figures that could be found in the literature.

Adolescent↗

[The stakes of force perseverance training and muscle structure training in rehabilitation. Recommendations of the German Federation for Prevention and Rehabilitation of Heart-Circulatory Diseases e.v].

While aerobic endurance training has been a substantial part of international recommendations for cardiac rehabilitation during the last 30 years, there is still a rather reserved attitude of the medical community to resistance exercise in this field. Careful recommendations for resistance exercise in cardiac patients was only published a few years ago. It has been taken for granted that strength exercise elicits a substantial increase in blood pressure and thus imposes, especially in cardiac patients, a risk of potentially fatal cardiovascular complications. Results of the latest studies show that the existing recommended overcaution is not justified. Strength exercise can indeed result in extreme increases of blood pressure, but this is not the case for all loads of this kind. The actual blood pressure response to strength exercise depends on the isometric component, the exercise intensity (load or resistance used), muscle mass activated, the number of repetitions in the set and/or the duration of the contraction as well as involvement of Valsalva maneuver. Intra arterially performed blood pressure measurements during resistance exercise in patients with heart disease showed that strength training carried out at low intensities (40-60% of MVC) and with high numbers of repetitions (15-20) only evokes a moderate increase of blood pressure comparable with blood pressure measures induced by moderate endurance training. If used properly and performed accurately, individually dosed, medically supervised and controlled through experienced sport therapists, a dynamic resistance exercise is-at least for a certain group of patients-not associated with higher risks than an aerobic endurance training and can in addition to endurance training improve muscle force and endurance, have a positive influence on cardiovascular function, metabolism, cardiovascular risk factors as well as psychosocial well-being and overall quality of life. However, with respect to currently available data, resistance exercise cannot be generally recommended for all groups of patients. The appropriate kind and execution of training is highly dependent on current clinical status, cardiac capacity as well as possible accompanying diseases of the patient. Most of the studies carried out up to date included small samples of middle-aged male patients with almost normal levels of aerobic endurance performance and good left ventricular function. Data is missing for risk groups, older patients and women. Therefore, an integration of dynamic resistance exercises in cardiac rehabilitation can only be recommended without hesitation for CHD patients with high physical capacity (good myocardial function, revascularized). Since patients with myocardial ischemia and/or low left ventricular functioning might develop wall motion disturbances and/or dangerous ventricular arrhythmia when performing resistance exercises, prevalence of the following conditions is recommend: moderate to high LV-function, high physical performance (>5-6 metabolic equivalents= >1.4 watts/kg body weight) in absence of angina pectoris symptoms or ST-depression, by maintained current medication. In the proposed recommendations, a classification of risks for resistance training in cardiac rehabilitation is being made based on current data and is complemented by specific recommendations for particular groups of patients and detailed guidelines for setup and completion of the therapy program.

Blood Pressure↗

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

Recommendations for resistance exercise in cardiac rehabilitation. Recommendations of the German Federation for Cardiovascular Prevention and Rehabilitation.

Aerobic endurance training has been an integral component of the international recommendations for cardiac rehabilitation for more than 30 years. Notwithstanding, only in recent years have recommendations for a dynamic resistance-training program been cautiously put forward. The perceived increased risk of cardiovascular complications related to blood pressure elevations are the primary concern with resistance training in cardiac patients; recent studies however have demonstrated that this need not be a contraindication in all cardiac patients. While blood pressure certainly may rise excessively during resistance training, the actual rise depends on a variety of controllable factors including magnitude of the isometric component, the load intensity, the amount of muscle mass involved as well as the number of repetitions and/or the load duration. Intra-arterial blood pressure measurements in cardiac patients have demonstrated that that during low-intensity resistance training [40-60% maximum voluntary contraction (MVC)] with 15-20 repetitions, only modest elevations in blood pressure are revealed, similar to those seen during moderate endurance training. When properly implemented by an experienced exercise therapist, in specific patient groups an individually tailored, medically supervised dynamic resistance training program carries no inherent higher risk for the patient than aerobic endurance training. As an adjunct to endurance training, in selected patients, resistance training can increase muscle strength and endurance, as well as positively influence cardiovascular risk factors, metabolism, cardiovascular function, psychosocial well-being and quality of life. According to present data, resistance training is however not recommended for all patient groups. The appropriate training method and correct performance are highly dependent on each patient's clinical status, cardiac stress tolerance and possible comorbidities. Most studies have used middle-aged men of average normal aerobic performance capacity and with good left-ventricular (LV) function. Data are lacking for high-risk groups, women and older patients. With the current knowledge it is reasonable to include resistance training without any restraints as part of cardiac rehabilitation programs for coronary artery disease (CAD) patients with good cardiac performance capacity (i.e., revascularised and with good myocardial function). As patients with myocardial ischaemia and/or poor left ventricular function may develop wall motion disturbances and/or severe ventricular arrhythmias during resistance exercise, the following criteria are suggested for resistance training: moderate-to-good LV function, good cardiac performance capacity [>5-6 metabolic equivalents of oxygen consumption (METS)=1.4 watt/kg body weight], no symptoms of angina pectoris or ST segment depression under continued maintenance of the medical therapy. Based on available data, this article presents recommendations for risk stratification in cardiac rehabilitation programs with respect to the implementation of dynamic resistance training. Additional recommendations for specific patient groups and detailed directions showing how to structure and implement such therapy programs are presented as well.

Cardiac Rehabilitation↗

Reduction of blood pressure response during strength training through intermittent muscle relaxations.

UNLABELLED: The increase in blood pressure during training is a disadvantage of strength training in the elderly. To reduce this effect it is generally recommended to apply lower levels of relative muscle strength with longer contraction durations or higher number of repetitions (continuous mode (CM), e. g. 50% of maximal strength, 10 to 15 repetitions without pauses). Alternatively, higher contraction forces could be combined with frequent periods of muscle relaxation and fewer repetitions (intermittent mode (IM), e. g. 80% of maximal strength, 8 repetitions consisting of 1.5 s concentric contraction, 1.5 s eccentric contraction and 3 s pause). We compared the blood pressure effects of both approaches during leg press exercise in two age groups (10 subjects aged 22 to 42 y, 9 subjects aged 60 to 72 y). Blood pressure was measured continuously by a non-invasive method (FINAPRES, Ohmeda 2300, Englewood USA). RESULTS: 1. The age of the subjects had no significant influence on the slopes of blood pressure increase during the different exercise modes. 2. The frequent insertion of short (3 s) periods of muscle relaxation (IM) decreased the blood pressure response more effectively than a reduction in contraction strength alone (CM). Short muscle relaxations have an immediate, mechanical effect on blood pressure and they allow a metabolic recovery which attenuates the trend of blood pressure increase.

Adult↗

[Significance of physical training on prevention in elderly patients].

The loss of strength, coordination, endurance, and flexibility with increasing age is only partly due to the aging process itself. A major factor is physical activity, i.e. the influence of implicit or explicit training stimuli. All elements of physical performance can be improved through training even in the very old, if the intensity and frequency of training are adequate. For the elderly, strength and coordination are particularly important elements of training since they constitute a prerequisite for an independent way of living. To minimize the cardiovascular risks during strength training, we developed and tested a new method which leads to significantly smaller increases in blood pressure than conventional approaches.

Aged↗

Cytotoxic and mutagenic effects, particle size and concentration analysis of diesel engine emissions using biodiesel and petrol diesel as fuel.

Diesel engine exhaust particles (DEP) contribute substantially to ambient air pollution. They cause acute and chronic adverse health effects in humans. Biodiesel (rapeseed oil methyl ester. RME) is used as a "green fuel" in several countries. For a preliminary assessment of environmental and health effects of RME, the particulate-associated emissions from the DEP of RME and common fossil diesel fuel (DF) and their in vitro cytotoxic and mutagenic effects were compared. A test tractor was fuelled with RME and DF and driven in a European standard test cycle (ECE R49) on an engine dynamometer. Particle numbers and size distributions of the exhausts were determined at the load modes "idling" and "rated power". Filter-sampled particles were extracted and their cytotoxic properties tested using the neutral red assay. Mutagenicity was tested using the Salmonella typhimurium/microsome assay. Despite higher total particle emissions, solid particulate matter (soot) in the emissions from RME was lower than in the emissions from DF. While the size distributions and the numbers of emitted particles at "rated power" were nearly identical for the two fuels, at "idling" DF emitted substantially higher numbers of smaller particles than RME. The RME extracts caused fourfold stronger toxic effects on mouse fibroblasts at "idling" but not at "rated power" than DF extracts. The extracts at both load modes were significantly mutagenic in TA98 and TA100. However, extracts of DF showed a fourfold higher mutagenic effect in TA98 (and twofold in TA100) than extracts of RME. These results indicate benefits as well as disadvantages for humans and the environment from the use of RME as a fuel for tractors. The lower mutagenic potency of DEP from RME compared to DEP from DF is probably due to lower emissions of polycyclic aromatic compounds. The higher toxicity is probably caused by carbonyl compounds and unburned fuel, and reduces the benefits of the lower emissions of solid particulate matter and mutagens from RME.

Animals↗

Mutagenicity of diesel exhaust particles from two fossil and two plant oil fuels.

Particulate matter of diesel engine exhaust from four different fuels was studied for content of polynuclear aromatic compounds and mutagenic effects. Two so-called biodiesel fuels, rapeseed oil methylesters (RME) and soybean oil methylesters (SME), were compared directly with two fossil diesel fuels with the normal (DF) and a low sulfur content (LS-DF). Diesel exhaust particles were sampled on filters from the diluted and cooled exhaust of a test engine at five different speeds and loads. Filters were weighed for total particulate matter, Soxhlet extracted with dichloromethane and the content of insoluble material determined. The soluble organic fraction was analysed for polynuclear aromatic compounds. Mutagenicity was determined using the Salmonella typhimurium/mammalian microsome assay with strains TA98 and TA100. Compared with DF, the exhaust particles of LS-DF, RME and SME contained less insoluble material, which consisted mainly of the carbon cores of diesel exhaust particles. The concentrations of individual polynuclear aromatic compounds varied widely among the different exhaust extracts, but total concentrations of the compounds were approximately double for DF and SME compared with LS-DF and RME. In TA98 significant increases in mutation rates were obtained for the soluble organic fractions of all fuels for engines running at full speed (load modes A and D), but for DF revertants were 2- to 10-fold more frequent as compared with LS-DF, RME and SME. Revertant frequencies for DF and partly for LS-DF were also elevated in TA100, while RME and SME gave no significant increase in mutations. The results indicate that diesel exhaust particles from RME, SME and LS-DF contain less black carbon and total polynuclear aromatic compounds and are significantly less mutagenic in comparison with DF. A high sulfur content of the fuel and high engine speeds (rated power) and loads are associated with an increase in mutagenicity of diesel exhaust particles.

Chromatography, High Pressure Liquid↗

Origin of back pain during bedrest: A new hypothesis.

Back pain during bed rest has frequently been reported. Until recently, studies concentrated mainly on length changes of the spine. Functional aspects such as reduced movements of the back, although anecdotally reported, could neither be quantified nor were they taken into account as a potential cause of back pain. In the present study the geometry of the spinal columns of eight healthy men was continuously recorded over 24 h before, during, and after a seven-day 6 degree head-down tilt period (Series 1). The approach is based on the measurement of skin distances between four pairs of miniaturized ultrasound transmitters and receivers fixed on the back in parallel to the thoracic and lumbar spine. After a four-week break, the entire study was repeated with the same subjects (Series 2). The major findings are: 1. The length increase of the spine segments investigated was virtually identical in both series. 2. During the bedrest period significantly greater pain occurred in Series 1 as compared to Series 2. Pain was generally confined to the lumbar region about 10 cm lateral of the spinous processes. 3. Pain was most prominent when trunk motions were minimal, while movements over the maximal range of the spine transiently reduced the pain remarkably. 4. During bed rest, the amplitude of voluntary movements of the lumbar segment was reduced in particular during Series 1. It is concluded that back pain during bed rest is induced by reduced amplitudes of spine movements rather than by increases in the spine length. It is suggested that isometric muscle contractions of low intensity are a primary course of back pain. Regular, slow, large-amplitude movements of the spine are recommended as a countermeasure.

Adult↗

Reduction of G-box binding factor DNA binding activity, but not G-box binding factor abundance, causes the downregulation of RBCS2 expression during early tomato fruit development.

The downregulation of RBCS2 promoter activity during tomato fruit development has been investigated by transient gene expression. A major drop in promoter activity occurs between 5 and 25 mm fruit diameter, corresponding to the late cell division to early cell enlargement phase. This drop is abolished by a mutation of the single G-box element necessary for high RBCS2 promoter activity in young tomato fruit. The G-box binding activity of fruit nuclear and total protein extracts drops concomitantly with the reduction of RBCS2 promoter activity while G-box binding factor expression is not affected. The data indicate that the developmental signal that downregulates the RBCS2 promoter acts on the regulation of DNA binding activity of constitutively expressed G-box binding factors.

Arabidopsis↗

Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol.

Oxidative theory of atherosclerosis implies that plasma levels of lipophilic antioxidants might serve as indicators of lipoprotein oxidation in the arterial wall and as markers of the development of atherosclerosis. However, it is unknown whether the measurement of plasma antioxidants is able to reflect atherogenesis or its risk. In order to assess whether the levels of lipophilic antioxidants in human plasma can discriminate between subjects with and without atherosclerosis, we measured the lipophilic antioxidants alpha-tocopherol, gamma-tocopherol, alpha-carotene, beta-carotene and ubiquinol-10 in plasma of 34 patients with coronary heart disease (CHD) and in 40 control subjects. We found that alpha-carotene and gamma-tocopherol were significantly lower in plasma of CHD patients compared to controls. This decrease was significantly independent of whether the antioxidants were expressed as its absolute amounts in plasma (P < 0.001 for alpha-carotene, and P = 0.001 for gamma-tocopherol) or normalized to plasma lipids (P < 0.001 for both). In contrast, beta-carotene was only lower in plasma of CHD patients in comparison to controls, when normalized to the lipids (P = 0.02). Independent contributions of different parameters to the variation in these plasma antioxidants were estimated using multiple regression approach. The analysis showed that both the decrease in alpha-carotene and the decrease in gamma-tocopherol were significantly associated only with the presence of CHD (P < 0.001 for each regression), while the decrease in beta-carotene was significantly related to the presence of hyperlipidaemia (P < 0.001). In striking contrast, no decrease in plasma alpha-tocopherol and ubiquinol-10 was detected in the patient group independently of how these antioxidants were expressed. These data suggest that plasma levels of alpha-carotene and gamma-tocopherol may represent markers of atherosclerosis in humans. Measuring these antioxidants may be of clinical importance as a practical approach to assess atherogenesis and/or its risk.

Adult↗

Cardiac output, leg blood flow and oxygen uptake during foot plantar flexions.

When studying the adjustment of muscle perfusion during exercise, the influence of central factors (e.g. blood volume, central blood pressure and venous return) can be reduced by choosing small muscle groups. In the present study parallel determinations of cardiac output (CO), leg blood flow (LBF) and pulmonary oxygen (VO2) uptake were performed in 9 healthy male subjects at the onset and cessation of dynamic foot plantar flexions. The volunteers exercised with both feet for 5 minutes at 3 different resistances corresponding to 6%, 18% and 30% of the mean maximal voluntary contraction. Doppler measurements at the aortic root and in the femoral artery were utilized to estimate CO and LBF. Oxygen uptake was analyzed breath-by-breath as the difference between inspired and expired oxygen volumes. Within the first 10 s of exercise LBF increased from 400 ml x min(-1) to about 1,000 ml x min(-1) at all exercises intensities. During the subsequent 5 minutes of exercise, LBF decreased to about 800 ml x min(-1) at the lowest intensity. By contrast, it increased to about 1,900 ml x min(-1) at the highest intensity. The changes in CO during exercise were quantitatively identical with the changes in LBF. The present results suggest that the fine adjustment of muscle blood flow and muscle metabolism starts only after a fast and uniform circulatory on response. The second component may lead to leg perfusion values above, at or below the initial peak perfusion levels. The off-transients of LBF displayed no comparable fast responses. They were slower than the recovery kinetics of any cardiovascular parameter measured in the present study.

Adult↗

Comparison between the physiological response to roller skiing and in-line skating in biathletes.

PURPOSE: Roller skiing is frequently used in Nordic disciplines during the off-season periods. Recently, in-line skating has become a potential alternative. In the present study, the responses of heart rate, oxygen uptake, respiratory exchange ratio, and lactic acid concentration to roller skiing and in-line skating were compared in competitive biathletes. METHODS: Eight male subjects performed three tests with both devices on a hilly outdoor track. They were requested to adjust their speed in such a way that the following criteria were met: intensity 1, lactate concentration about 2 mmol x L(-1); intensity 2, lactate concentration about 4 mmol x L(-1); AND intensity 3, maximal speed. RESULTS: Though the subjects were not experienced in-line skaters, all managed to adjust the required intensities. This was achieved through increased velocities during in-line skating. Independent of the exercise intensity the differences in speed ranged between 1.0 and 1.4 m x s(-1). The relationships between lactic acid concentration, oxygen uptake, respiratory exchange ratio, and heart rate were not influenced by the test device. The respiratory exchange ratio amounted to 0.88, 0.95, and 1.02 for intensities 1 to 3, respectively. CONCLUSIONS: These results show that in-line skating can be regarded as an alternative to roller skiing for off-seasonal training in Nordic disciplines. A potential advantage of in-line skating is that aerobic training intensities can be obtained at competitive velocities.

Adult↗

Developmental neuropathology and the precursors of schizophrenia.

Changes in the manifestation of vulnerability to schizophrenia across the lifespan may hold important clues about aetiology. They may also illustrate some general principles about the nature of neurodevelopmental processes. Within the framework of a neural diathesis-stress model, we review findings on the precursors of schizophrenia and schizotypal personality disorder. The findings suggest that there are critical developmental periods for the manifestation of dysfunction and that, within certain domains of behaviour, there is a temporal disjunction between the onset of the neuropathology and its expression. It also appears that the diathesis for schizophrenia involves polymorphic behavioural expression, such that it can be manifested in multiple domains - motoric, cognitive and socio-emotional. Taken together, the data on the longitudinal course of schizophrenia indicate that the expression of the diathesis is moderated by central nervous system maturational processes. One putative moderating system, the hypothalamic-pituitary-adrenal (HPA) axis, is discussed, and implications for preventive intervention are explored.

Age Factors↗

[Differential diagnosis of distal peripheral nerve compression syndrome of the tibial nerve. Case report of primitive neuroectodermal tumor].

Tumors of the tibial nerve are not sufficiently taken into account in the diagnosis of tarsal tunnel syndromes (TTS). They may present with atrophy of the plantar flectors and with disturbances of sensory functions, but far more commonly with pain. Diagnosis is often only achieved after 1-2 years. Taking tumors into account when examining patients presenting with TTS may lead to a more rapid diagnosis and to improvement in patients' prognoses. We present the case of a 37-year-old female in whom a primitive neuroectodermal tumor (PNET) was found to be the cause of long-standing pain in the right foot.

Adult↗

Leg blood flow during slow head-down tilt with and without leg venous congestion.

The effects of slow changes in body position on leg blood flow (LBF) were studied in nine healthy male subjects. Using a tilt table, sitting volunteers were tilted about 60 degrees backwards to a supine position within 40 s. To modify the venous filling in the legs, the tilt manoeuvre was repeated with congestion of the leg veins induced by two thigh cuffs inflated to a subdiastolic pressure of 60 mmHg. Doppler measurements in the femoral artery were used to estimate LBF. Additional Doppler measurements at the aortic root in five of the subjects were taken for the determination of cardiac output. The LBF was influenced by body position. In the control experiment it increased from 500 ml x min(-1) in the upright to 780 ml x min(-1) after 15 min in the supine position. A mean maximal value of 950 ml x min(-1) was observed 20 s after the tilt. Heart rate remained almost constant during the tilt phase, whereas stroke volume increased from 90 ml to 120 ml and it remained at that level after the cessation of the tilt. Congestion of the leg veins had no significant effect on heart rate, stroke volume and mean blood pressure. However, it increased vascular resistance of the leg during and after the tilt. After 15 min in the tilted position LBF amounted to 600 ml x min(-1). The results suggest that the filling of the leg veins is inversely related to leg blood flow. The most likely mechanism underlying this observation is a local effect of venous filling on vasomotor tone.

Adult↗