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Biomedical subjects

R Kaiser

Publications and source records attributed to R Kaiser.

At least 91 records · Page 5Linked to original sources

The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994-98: a prospective study of 656 patients.

Seven hundred and nine patients fell ill in southern Germany (Baden-Württemberg) after infection with the tick-borne encephalitis (TBE) virus between 1994 and 1998. Detailed clinical and epidemiological data on TBE were available for 656 patients. A biphasic course of the disease occurred in 485 patients (74%). TBE presented as meningitis in 320 patients (49%), as meningoencephalitis in 270 (41%) and as meningoencephalomyelitis in 66 (10%). Eight of the patients (1.2%) died from TBE. Four hundred and forty-five patients (68%) had noticed a tick bite and the first symptoms occurred, on average, 7 days later. The most frequent neurological symptoms were impairment of consciousness (31%), ataxia (18%) and paresis of the extremities (15%) and cranial nerves (11%). Laboratory investigations revealed leucocytosis in the peripheral blood in 224 out of 392 patients (74%), elevation of the erythrocyte sedimentation rate in 223 out of 245 (91%), increased C-reactive protein in 127 out of 155 (82%), pleocytosis in the CSF of all patients tested, damage of the blood-CSF barrier in 255 out of 322 (79%), abnormalities in EEG in 165 out of 214 (77%) and abnormalities in MRI in 18 out of 102 (18%). In general, adolescents up to 14 years of age had a more favourable course of the disease than adults. Of 230 patients who were re-examined at a later time, 53 (23%) had moderate or severe sequelae. Patients with sequelae presented more frequently (P < 0.001) with impaired consciousness (Glasgow Coma Scale < 7), ataxia, pareses of the extremities or cranial nerves, a need for assisted ventilation, abnormal findings in MRI, pleocytosis > 300 cells/microl and impairment of the blood-CSF barrier (total protein > 600 mg/l). In view of the severity of the illness and the high frequency of sequelae, active immunization against TBE is recommended for all subjects living in and travelling to areas of risk. Prevention of TBE by post-exposure prophylaxis with hyperimmunoglobulins is less effective and therefore should be performed only when absolutely necessary.

Adolescent↗

Advantage of recombinant borrelial proteins for serodiagnosis of neuroborreliosis.

Two enzyme immunoassay (EIA) systems were compared for their ability to detect Borrelia burgdorferi sensu lato specific IgG and IgM antibodies and to differentiate between symptomatic (83 patients with neuroborreliosis) and asymptomatic seropositive subjects (80 healthy controls). Antibody concentrations were determined by EIA; the antigens used were either a sonicate of B. burgdorferi or three recombinant borrelial proteins: the 14-kDa flagellin fragment, the outer surface protein C (22 kDa) and the high molecular mass protein p83 (83 kDa). In the sonicate, EIA, IgG or IgM antibodies to B. burgdorferi, or both, were detected in all patients with neuroborreliosis and in all controls. Pre-absorption of sera with Treponema phagedenis sonicate diminished the sensitivity of detection of borrelial specific IgG (IgG or IgM or both) antibodies in patients with neuroborreliosis from 80 to 57% (100 to 82%) and in the controls from 100 to 32% (100 to 37%). While being specific for B. burgdorferi, the recombinant EIAs proved to be significantly more sensitive than the sonicate EIA: IgG or IgM, or both antibodies against any of the recombinant antigens were detected in 92% of patients with neuroborreliosis and in 24% of controls. The increase in sensitivity in patients with neuroborreliosis was mostly due to the higher detection rate of IgM antibodies in the recombinant EIA (77% versus 48% in the sonicate EIA), while IgG antibodies were demonstrated with similar frequencies in both EIA systems (57% versus 60%). It was concluded that the recombinant EIAs are superior to the sonicate EIA with pre-absorption of cross-reactive antibodies in the confirmation of an acute borrelial infection and in the differentiation between symptomatic and asymptomatic infections.

Acute Disease↗

Kinematic dynamos surrounded by a stationary conductor.

We investigate kinematic dynamos in cylinders and spheres surrounded by an insulator. The flow volume is divided into an inner region, in which the conducting fluid is in motion, and an outer region enclosing the inner one, in which the conductor is at rest. The dependence of the critical magnetic Reynolds number on the thickness of the outer conducting shell is discussed as well as implications for the design of experimental dynamos.

Journal Article↗

Bacterial growth state distinguished by single-cell protein profiling: does chlorination kill coliforms in municipal effluent?

Municipal effluent is the largest reservoir of human enteric bacteria. Its public health significance, however, depends upon the physiological status of the wastewater bacterial community. A novel immunofluorescence assay was developed and used to examine the bacterial growth state during wastewater disinfection. Quantitative levels of three highly conserved cytosolic proteins (DnaK, Dps, and Fis) were determined by using enterobacterium-specific antibody fluorochrome-coupled probes. Enterobacterial Fis homologs were abundant in growing cells and nearly undetectable in stationary-phase cells. In contrast, enterobacterial Dps homologs were abundant in stationary-phase cells but virtually undetectable in growing cells. The range of variation in the abundance of both proteins was at least 100-fold as determined by Western blotting and immunofluorescence analysis. Enterobacterial DnaK homologs were nearly invariant with growth state, enabling their use as permeabilization controls. The cellular growth states of individual enterobacteria in wastewater samples were determined by measurement of Fis, Dps, and DnaK abundance (protein profiling). Intermediate levels of Fis and Dps were evident and occurred in response to physiological transitions. The results indicate that chlorination failed to kill coliforms but rather elicited nutrient starvation and a reversible nonculturable state. These studies suggest that the current standard procedures for wastewater analysis which rely on detection of culturable cells likely underestimate fecal coliform content.

Antibodies, Bacterial↗

Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure.

BACKGROUND: The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF. METHODS AND RESULTS: Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24+/-4%) or a control group (n=10, LVEF 23+/-3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endothelium-independent vasodilation remained unaltered (271% versus 281%, P=NS). Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203% (from 152+/-79 to 461+/-104 mL/min, P<0.05 versus control group) and the inhibiting effect of L-NMMA increased by 174% (from -46+/-25 to -126+/-19 mL/min, P<0.05 versus control group). Peak oxygen uptake increased by 26% (P<0.01 versus control group). The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow (r=0.64, P<0. 005). CONCLUSIONS: Regular physical exercise improves both basal endothelial nitric oxide (NO) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF. The correction of endothelium dysfunction is associated with a significant increase in exercise capacity.

Blood Flow Velocity↗

Use of transition probabilities to estimate the effect of smoking on the duration of episodes of respiratory symptoms in diary data: the Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA).

Incompletely documented symptom episodes pose methodological problems in the analysis of diary data. The aim of this study was to develop a method of estimating the average durations of symptomatic and nonsymptomatic episodes, respectively, coping with the problem of bias due to undocumented days and censored episodes that is found in most diary studies. The authors derived their outcome variables from a Markov model using transition probabilities. To evaluate this method, the authors assessed the impact of active smoking on the duration of episodes of bronchitis symptoms and the corresponding nonsymptomatic periods, respectively, using diary data (1992-1993) obtained from 801 participants in the Swiss Study on Air Pollution and Lung Diseases in Adults. Covariate-adjusted distribution curves for the mean durations of individual episodes were estimated by Cox regression. Median values for light smokers (<10 cigarettes/day) were 60.0 symptom-free days (95% confidence interval (CI) 42.0-78.5) and 4.0 symptomatic days (95% CI 3.0-6.0), respectively, compared with medians of only 21.0 days (95% CI 16.2-29.8) for periods without bronchitis symptoms and 6.0 days (95% CI 4.9-9.0) for episodes of bronchitis symptoms in heavy smokers (> or =30 cigarettes/day). The authors suggest that the Markov method is a feasible approach to the assessment of long term effects of smoking and environmental risk factors on the average duration of symptomatic and nonsymptomatic respiratory episodes.

Adult↗

In vitro cytopathogenicity of the human immunodeficiency virus (HIV)-1 predicts survival in HIV-infected hemophiliacs independent from CD4 cell count.

In addition to quantification of viral load the graded cytopathogenicity of the human immunodeficiency virus may provide prognostic information for the course of HIV infection. However, the prognostic value of graded cytopathogenicity in addition to the CD4 count has not been evaluated in a large longitudinal study. Therefore a total of 216 HIV-seropositive hemophiliacs have been followed up from 1985 to 1998 (mean follow-up 70.4 +/- SD 26 months, median 72, range: 12 to 120 months). In vitro virulence was determined according to cytopathic effects on freshly isolated PBMC of healthy donors and graded from A (strongest cytopathogenic effect) to D (no cytopathic isolate effect). Survival was analyzed among patients with different virus isolates by Kaplan-Meier statistics (log rank) and factors independently associated with decreased survival were analyzed by Cox hazard regression analysis. - A virus isolate A was found in 22 (10.2%) patients, a virus isolate B was found in 21 (9.3%) patients, a virus isolate C was found in 9 (4.2%) and a virus isolate D was found in 10 (4.2%) patients. Mean survival times were 48 months (95% Confidence Interval (CI) = 36 - 60) in patients with isolate A, 72 months (CI = 36 - 108) with isolate B, 84 months (CI = 48-120) with isolate C, 72 months (60 - 96) with isolate D and 96 months (CI = 96 - 108) in patients with a negative virus culture (p < 0.001). Cox regression analysis indicated significant associations with outcome for young age (p <0.001), positive virus culture (p < 0.0001) and CD4 count (p < 0.0001) as independent predictors of survival. The presence of an isolate A revealed the strongest odds ratio (6.3, 95% CI 2.9-13.2). Our data indicate that the presence of a virus isolate A represents a strong risk factor for mortality in the course of HIV infection. Besides quantification of viral load and CD4 count, the graded cytopathogenicity may provide additional information for early and aggressive antiretroviral treatment, since the mean survival in patients with cytopathogenic virus isolates is reduced significantly.

Acquired Immunodeficiency Syndrome↗

[Paraneoplastic cerebellar degeneration in Hodgkin's disease].

HISTORY AND CLINICAL FINDINGS: A 30-year-old previously healthy man suddenly developed double vision, unsteady gait and some difficulty in speech articulation. Within 4 weeks he had become markedly ataxic, unable to walk, stand or sit down unaided. Neurological examination indicated a severe cerebellar syndrome. There were no other abnormal findings on physical examination. INVESTIGATIONS: There was no pleocytosis and no oligoclonal bands in cerebrospinal fluid (CSF). A test for anti-Purkinje cell antibodies was negative in both CSF and serum. Computed tomography and nuclear magnetic imaging (NMI) of the brain were normal. TREATMENT AND COURSE: As a para- or postinfectious or paraneoplastic process was suspected. I.v. immunoglobulin and oral corticosteroids were administered, but without improvement. 13 month later, a mediastinal mass was noted on a chest radiogram. This led to the diagnosis of a stage IA Hodgkin's disease. Retrospectively the cerebellar degeneration was most likely a paraneoplastic change related to the Hodgkin's disease. However, an independent second disease cannot be excluded. While the treatment of Hodgkin's disease was successful, the neurological symptoms remained unchanged. Severe cerebellar atrophy was demonstrated on NMI. CONCLUSION: In case of cerebellar atrophy of undetermined aetiology a paraneoplastic cause should be considered and an underlying malignant disease looked for.

Adult↗

De novo expression of the alpha5beta1-fibronectin receptor in HT29 colon-cancer cells reduces activity of C-SRC. Increase of C-SRC activity by attachment on fibronectin.

Changes in integrin expression during malignant transformation have been observed in many tumors. Colon-carcinoma cells show reduced expression or even loss of the alpha5beta1 integrin compared to normal or adenoma cells. To determine the significance of absent alpha5beta1 integrin signaling, we transfected the cDNA coding for the alpha5 integrin sub-unit into the human colon-carcinoma cell line HT29, which constitutively lacks this subunit but does express the beta1 subunit. We show here that the newly expressed fibronectin receptor alpha5beta1 generates multiple signals, causing marked changes in cytoskeletal arrangements within a few minutes of adhesion to fibronectin. Cells expressing the alpha5beta1 integrin exhibit the formation of actin stress fibers and focal adhesions, as well as the induction of tyrosine phosphorylation of several proteins, within 10 min. We identified the focal adhesion kinase pp125FAK and the cytoskeletal protein paxillin as major phosphorylation substrates in these cells. These proteins remained hypophosphorylated when alpha5-negative control cells were plated on fibronectin. The tyrosine kinase pp60c-src, regarded as central in the regulation of cellular proliferation and constitutively over-expressed in HT29 and in colon-carcinoma cells, showed reduced intrinsic kinase activity in unstimulated HT29alpha5 cells. In contrast, fibronectin-induced signaling through alpha5beta1 increased pp60c-src activity. Moreover, immunoprecipitation of pp60c-src from extracts of HT29alpha5 cells cultivated on fibronectin for 20 min revealed complex formation of pp60c-src and tyrosine-phosphorylated pp125FAK. Our data suggest that de novo expression of the alpha5beta1 integrin in HT29 colon-cancer cells restores signaling via pp125FAK and pp60c-src. Thus, loss of this receptor during malignant transformation may contribute to tumor-cell autonomy, while reduced activity of pp60c-src in HT29alpha5-cells may participate directly in growth control.

Cell Adhesion↗

Analysis of the intrathecal immune response in neuroborreliosis to a sonicate antigen and three recombinant antigens of Borrelia burgdorferi sensu stricto.

The intrathecal synthesis of borrelial-specific IgM- and IgG-antibodies was studied in 67 patients with neuroborreliosis and in 14 patients with neurosyphilis (controls). Antibody concentrations in serum and in the cerebrospinal fluid were determined by an enzyme immunoassay (EIA) using, as antigens, a sonicate of Borrelia burgdorferi, the recombinant 14 kDa flagellin fragment, the outer surface protein C (22 kDa), and the high molecular mass protein p83 (83 kDa). In the sonicate EIA, IgG- and/or IgM-antibodies to Borrelia burgdorferi in serum were detected in all patients with neuroborreliosis and in 71% of patients with neurosyphilis. Intrathecal synthesis of borrelial-specific IgG- and/or IgM-antibodies was demonstrated in 82% of patients with neuroborreliosis and in 71% of patients with neurosyphilis. Immunoglobulin G- and/or IgM-antibodies in serum against any of the recombinant antigens were detected in 92% of patients with neuroborreliosis and in none of those with neurosyphilis. Intrathecal synthesis of IgG- and/or IgM-antibodies to individual recombinant antigens was demonstrated in 67% of patients with neuroborreliosis and in none of those with neurosyphilis. The sensitivity of the recombinant antigens in serum was almost equal to that of the sonicate EIA, whereas the recombinant antigens were clearly less sensitive in the estimation of the intrathecal specific immune response. It was concluded that in suspected cases of neuroborreliosis, the estimation of high specific antibodies in the recombinant EIA will be helpful in confirming the diagnosis.

Antibodies, Bacterial↗

Neuroborreliosis.

Neuroborreliosis, a manifestation of infection with the spirochete Borellia burgdorferi, has become the most frequently recognised arthropod-borne infection of the nervous system in Europe and the USA. The best criterion of an early infection with B. burgdorferi is erythema migrans (EM), but this is present in only about 40-60% of patients with validated borreliosis. Therefore use of the duration of the disease as a classification criterion for neuroborreliosis is increasing, the chronic form being distinguished from the acute when symptoms persist for more than 6 months. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. In Europe, meningopolyradiculoneuritis (Bannwarth's syndrome) represents the most common manifestation of acute neuroborreliosis, with the facial nerve being affected much more frequently than the other cranial nerves. Clinical symptoms affecting the central nervous system are rarely observed and then mostly in chronic courses. By far the most common manifestation of chronic neuroborreliosis is encephalomyelitis with spastic-ataxic disturbances and a disturbance of micturition. The current diagnosis of neuroborreliosis is a clinical one, which has to be confirmed by laboratory testing. In most patients, examination of the cerebrospinal fluid (CSF) reveals lymphocytic pleocytosis, damage to the blood-CSF-barrier and an intrathecal synthesis immunoglobulin (Ig) M, IgG, and sometimes IgA. Confirmation of a borrelial infection of the nervous system requires demonstration of an intrathecal synthesis of borrelial-specific antibodies in the CSF or detection of borrelial DNA in the CSF by polymerase chain reaction (PCR). There is no generally accepted therapeutic regime for the treatment of neuroborreliosis, but recent studies have shown ceftriaxone 2 g/day and cefotaxime 6 g/day to be effective in acute and chronic courses. Penicillin G 20 mega units/day and doxycycline 200 mg/day may be suitable for uncomplicated meningopolyneuritis, without involvement of the central nervous system. The durationof treatment--at least 2 weeks in the acute forms and 3 weeks in the chronic forms of neuroborreliosis--is very important for successful treatment. Corticosteroids are recommended only for patients with severe pain that does not respond to antibiotics an analgesics.

Borrelia Infections↗

Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study.

BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.

Acetylcysteine↗

Partial liquid ventilation in adult patients with ARDS: a multicenter phase I-II trial. Adult PLV Study Group.

OBJECTIVE: To evaluate the safety and efficacy of partial liquid ventilation (PLV) in adult patients with the acute respiratory distress syndrome (ARDS). SUMMARY BACKGROUND DATA: Previous studies have evaluated gas exchange and the safety of PLV in adult patients with severe respiratory failure whose gas exchange was partially provided by extracorporeal life support (ECLS). This is the first experience with adult patients who were not on ECLS. METHODS: Intratracheal perflubron in a total dose of 30.1 +/- 7.1 ml/kg was administered over a period of 45 +/- 9 hours to nine adult patients with mean age = 49 +/- 4 years and mean PaO2/FiO2 ratio = 128 +/- 7 as part of a prospective, multicenter, phase I-II noncontrolled trial. RESULTS: Significant decreases in mean (A-a)DO2 (baseline = 430 +/- 47, 48 hour = 229 +/- 17, p = 0.0127 by ANOVA) and FiO2 (baseline = 0.82 +/- 0.08, 48 hour = 0.54 +/- 0.06, p = 0.025), along with an increase in mean SvO2 (baseline = 75 +/- 3, 48 hour = 85 +/- 2, p = 0.018 by ANOVA) were observed. No significant changes in pulmonary compliance or hemodynamic variables were noted. Seven of the nine patients in this study survived beyond 28 days after initiation of partial liquid ventilation whereas 5 patients survived to discharge. Three adverse events [hypoxia (2) and hyperbilirubinemia (1)] were determined to be severe in nature. CONCLUSIONS: These data suggest that PLV may be performed safely with few related severe adverse effects. Improvement in gas exchange was observed in this series of adult patients over the 48 hours after initiation of PLV.

Adult↗

Roles of DnaK and RpoS in starvation-induced thermotolerance of Escherichia coli.

DnaK is essential for starvation-induced resistance to heat, oxidation, and reductive division in Escherichia coli. Studies reported here indicate that DnaK is also required for starvation-induced osmotolerance, catalase activity, and the production of the RpoS-controlled Dps (PexB) protein. Because these dnaK mutant phenotypes closely resemble those of rpoS (sigma38) mutants, the relationship between DnaK and RpoS was evaluated directly during growth and starvation at 30 degrees C in strains with genetically altered DnaK content. A starvation-specific effect of DnaK on RpoS abundance was observed. During carbon starvation, DnaK deficiency reduced RpoS levels threefold, while DnaK excess increased RpoS levels nearly twofold. Complementation of the dnaK mutation restored starvation-induced RpoS levels to normal. RpoS deficiency had no effect on the cellular concentration of DnaK, revealing an epistatic relationship between DnaK and RpoS. Protein half-life studies conducted at the onset of starvation indicate that DnaK deficiency significantly destabilized RpoS. RpoH (sigma32) suppressors of the dnaK mutant with restored levels of RpoS and dnaK rpoS double mutants were used to show that DnaK plays both an independent and an RpoS-dependent role in starvation-induced thermotolerance. The results suggest that DnaK coordinates sigma factor levels in glucose-starved E. coli.

Adaptation, Biological↗

[Tick-borne encephalitis transmitted by raw milk--what is the significance of this route of infection? Studies in the epidemic region of South-West Germany].

Despite the observation of TBE cases after consumption of raw milk from cows or goats, so far the proof of the alimentary route of human infection has not been possible. In the regions of southwestern Germany, where TBE is known to be endemic, milk-borne TBE infections have not yet been observed. To assess the significance of raw milk consumption for viral transmission, a cross-sectional study (114 forestry workers, 177 individuals exposed during their leisure-time activities, 170 non-exposed individuals) and a case-control study (50 TBE patients, 150 controls) were carried out. The results of the study show that both the time spent in the endemic region and also the professional exposure to ticks do influence TBE seroprevalence, whereas the consumption of raw milk (milk directly from the farmer) is no major risk factor for TBE infection or disease. Among leisure-time activities, only hunting has an effect comparable to the one of the professional exposure to ticks. Besides epidemiological data obtained in humans, serological investigations of cows were performed. Here it is shown that milk-producing animals are involved in the natural transmission of TBE virus. Since former studies had shown that TBE-viremic animals excrete the virus with the milk--although over a short period and in low concentrations--the occurrence of milk-borne TBE infections cannot be excluded in the endemic regions of south-western Germany. However, from the epidemiological point of view, their significance may be neglected. Vaccination has proven the most reliable means of TBE prevention, irrespective of the route of infection.

Animals↗