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Biomedical subjects

P Winkler

Publications and source records attributed to P Winkler.

At least 19 recordsLinked to original sources

Quantification of MRS data in the frequency domain using a wavelet filter, an approximated Voigt lineshape model and prior knowledge.

Quantification of MRS spectra is a challenging problem when a large baseline is present along with a low signal to noise ratio. This work investigates a robust fitting technique that yields accurate peak areas under these conditions. Using simulated long echo time (1)H MRS spectra with low signal to noise ratio and a large baseline component, both the accuracy and reliability of the fit in the frequency domain were greatly improved by reducing the number of fitted parameters and making full use of all the known information concerning the Voigt lineshape. Using an appropriate first order approximation to a popular approximation of the Voigt lineshape, a significant improvement in the estimate of the area of a known spectral peak was obtained with a corresponding reduction in the residual. Furthermore, this improved parameter choice resulted in a large reduction in the number of iterations of the least-squares fitting routine. On the other hand, making use of the known centre frequency differences of the component resonances gave negligible improvement. A wavelet filter was used to remove the baseline component. In addition to performing a Monte Carlo study, these fitting techniques were also applied to a set of 10 spectra acquired from healthy human volunteers. Again, the same reduced parameter model gave the lowest value for chi(2) in each case.

Computer Simulation↗

Early surgery for ruptured cerebral arteriovenous malformations.

Acute surgery on cerebral arteriovenous malformations (AVMs) has seldom been reported or used. We reviewed 49 patients of ages 2 months to 78 years (mean 32.8 years), 32 male (65%) and 17 female (35%), treated acutely (within 4 days of bleed) in Helsinki Neurosurgery during 1997-2002. The following variables were assessed in regards to the outcome (Glasgow outcome score; GOS; 2-3 months after bleed): age, sex, Hunt and Hess Grade (HH), Spetzler-Martin Grade (SMG), location of AVM, size of intraparenchymal haematoma (ICH), and presence of intraventricular haemorrhage (IVH). Most of the patients were in a poor clinical condition on admission (two thirds were HH 4-5). 45 (92%) patients underwent extirpation of AVM and evacuation of ICH, within 4 days after bleed. Over 55% had good functional outcome. GOS correlated significantly with HH (p = 0.001), age (p = 0.006), and IVH (p = 0.049). On the other hand, SMG, location of AVM, and size of haematoma did not significantly predict the outcome. Microneurosurgery with preoperative embolization has made possible the excision of 90% of AVMs. It is our experience that it can be done acute and early, and it saves lives as compared to natural history of cerebral AVMs or late surgery, and accelerates rehabilitation of the patients.

Adolescent↗

Effect of a dietary supplement containing probiotic bacteria plus vitamins and minerals on common cold infections and cellular immune parameters.

OBJECTIVE: A randomized, double-blind, placebo-controlled intervention study was carried out in order to investigate whether consumption of a dietary supplement containing probiotic bacteria plus vitamins and minerals over a period of at least three months in winter/spring affects the duration, frequency, and severity of symptoms of naturally acquired common cold infections as well as cellular immune parameters. METHODS: 477 healthy men and women (aged 36 +/- 13, mean +/- SD) who had not been vaccinated against influenza were randomly assigned to a group who received daily the probiotic multivitamin and mineral supplement (verum) or a placebo, for three (n = 239) or for 5.5 months (n = 238). Cellular immune response was determined in 60 participants per study group by flow cytometry before and after 14 days of supplementation. RESULTS: The incidence of respiratory tract infections regarded as being virally induced was 13.6% lower in the verum group compared to the placebo group (p = 0.07). During respiratory tract infection episodes, the subjects recorded common cold and influenza-like symptoms daily. All symptoms were reduced in the verum group. We found a relative reduction of 19% in the total symptom score (p = 0.12), 25% in influenza symptoms (p = 0.09), and 54% in the number of days with fever (p = 0.03). The duration of these infections was not affected. Leukocytes, lymphocytes, in particular T-lymphocytes including CD4+ and CD8+ cells, as well as monocytes were significantly higher increased in the verum group, during the first 14 days of supplementation compared to placebo. CONCLUSION: These data indicate that the intake of a dietary supplement containing probiotic bacteria plus vitamins and minerals during a period of at least three months in winter/spring may reduce the incidence and the severity of symptoms in common cold infections in otherwise healthy adults. This may be due to stimulated cellular immunity.

Adult↗

Periodic orbit theory for the Hénon-Heiles system in the continuum region.

We investigate the resonance spectrum of the Hénon-Heiles potential up to twice the barrier energy. The quantum spectrum is obtained by the method of complex coordinate rotation. We use periodic orbit theory to approximate the oscillating part of the resonance spectrum semiclassically and Strutinsky smoothing to obtain its smooth part. Although the system in this energy range is almost chaotic, it still contains stable periodic orbits. Using Gutzwiller's trace formula, complemented by a uniform approximation for a co-dimension-two bifurcation scenario, we are able to reproduce the coarse-grained quantum-mechanical density of states very accurately, including only a few stable and unstable orbits.

Journal Article↗

Increasing ozone over the Atlantic Ocean.

Ship-borne ozone (O3) measurements over the Atlantic Ocean during the period from 1977 to 2002 show that O3 trends in the northern mid-latitudes are small. In contrast, remarkably large O3 trends occur at low latitudes and in the Southern Hemisphere, where near-surface O3 has increased by up to a factor of 2. The likely cause is the substantial increase of anthropogenic emissions of nitrogen oxides (NOx) associated with energy use in Africa, which has added to NOx from biomass burning and natural sources.

Journal Article↗

Lymphocyte proliferation and apoptosis in HIV-seropositive and healthy subjects during long-term ingestion of fruit juices or a fruit-vegetable-concentrate rich in polyphenols and antioxidant vitamins.

OBJECTIVE: We investigated whether ingestion of polyphenols from fruit juices or a fruit-vegetable-concentrate affects lymphocyte proliferation and apoptosis in human immunodeficiency virus (HIV)-seropositive (HIV(+)) and HIV-seronegative (HIV(-)) subjects. DESIGN: Randomized, prospective pilot intervention study. SETTING: University of Bonn, Department of General Internal Medicine. SUBJECTS: A total of 23 HIV(+) subjects from the HIV outpatient clinic, 18 HIV(-) controls. INTERVENTIONS: Subjects ingested either 1 l of fruit juice or 30 ml of fruit-vegetable-concentrate daily for 16 weeks in addition to their regular diet. Lymphocyte proliferation and apoptosis were investigated in peripheral blood mononuclear cells at baseline, during 16-weeks of intervention, and after a 6-week washout. Proliferation was assessed by (3)H-thymidine incorporation and apoptosis by nuclear content as measured by flow cytometry. RESULTS: Supplementation of fruit juices increased phytohemagglutinin-induced lymphocyte proliferation (mitotic index) in HIV(+) patients from 18+/-16 to 40+/-34 (P=0.004) and in healthy controls from 27+/-16 to 51+/-21 (P=0.016). Apoptosis was not affected in HIV(+) patients, but rose in healthy controls from 9+/-10 to 34+/-11 (apoptotic index; P=0.001). Intervention with concentrate did not significantly alter proliferation and apoptosis in HIV(+) and HIV(-) subjects. CONCLUSIONS: Even though apoptosis did not change in HIV(+) subjects, ingestion of polyphenol-rich fruit juices might be favorable to HIV(+) patients due to enhanced proliferation, which could restore disturbances in T-cell homeostasis. In healthy controls, increased lymphocyte proliferation during juice consumption was counterbalanced by increased apoptosis.

Adult↗

[Ozone decline and UV increase].

The following results have been obtained from long-term observations on the ozone layer and UV at the Meteorological Observatory Hohenpeigenberg:The seasonally varying decline of the ozone layer determines the maximum exposure to UV. Since ozone decline shows the highest rates in the spring months the UV exposure has most strongly increased in this time of the year. This is especially important because in spring the human skin is not adapted to UV exposure. Weather changes from day to day can induce rapid ozone reductions in spring about -30% which in turn is followed by an increase in UV of about 40%. Clouds, especially the transparent cirrus clouds (high clouds consisting of ice particles) have increased in frequency during spring and fall while a decrease is observed in summer. This change in cloudiness reduces the daily UV dose in spring and fall while it is enhanced in summer. With increasing height above sea level UV rises by roughly 10% per 1000 m (rule of thumb). Snow reflects the UV-radiation by up to 80% enhancing the UV-doses at relevant conditions. Strong volcano eruptions destroy ozone in the stratosphere additionally during 1-2 years after the eruption. Therafter the ozone layer recovers. In April 1993, after the eruption of Mt. Pinatubo (1991), the UV burden was still 40% higher than average. Miniholes and streamers can appear unexpected on a short-time scale and cross over Central Europe within 1-2 days, thus enhancing UV irradiation. The human skin reacts to UV exposure depending on the type of skin. The campaign "Sonne(n) mit Verstand" of the Bavarian Ministries for Environment, for Health and for Education informs about the danger of UV radiation (see www.sonne-mit-ver-stand.de). The German Weather Service informs the public on present developments of the ozone layer and relevant topics byits ozone bulletin, which is also available via internet under (www.dwd.de/deFundE/Observator/MOHp/hp2/ozon/bulletin.htm).

Climate↗

Palliative treatment of unresectable bile duct tumours.

PURPOSE: Report on outcome of intraluminal high-dose-rate iridium-192 (HDR-Ir192) brachytherapy with or without external radiotherapy in patients with unresectable bile duct tumours suffering from symptoms of malignant obstructive jaundice. MATERIAL AND METHODS: Fourteen patients (mean age: 63 years) who were unsuitable for surgical resection on preoperative evaluation/laparotomy or inoperable due to poor general condition were referred for palliative radiotherapy. After percutaneous transhepatic drainage, HDR-Ir192 brachytherapy was performed with a single dose of 2.5 Gy. Brachytherapy was given twice a day with at least a 6-h interval for 2 days, 2 or 3 days apart, up to a total dose of 10 Gy. Five patients received small-volume external radiotherapy (RT) (45 - 50.4 Gy/1.8 Gy) additionally. RESULTS: Palliation with relief of the aggravating symptoms of obstructive jaundice was achieved in all patients. The actuarial 2-year survival rate of all patients was 11.9 % with a median survival of 6.5 months. Patients treated with brachytherapy alone had a median survival of 4.5 months as compared with 6.5 months after combined internal and external irradiation (log rank, P = 0.95). CONCLUSION: Patients with advanced unresectable bile duct cancer face a dismal prognosis; however, biliary drainage, and intraluminal brachytherapy with or without external RT, seem to be able to improve quality of life in the remaining time span.

Adult↗

Loss of oestrus, concealed ovulation and paternity confusion in free-ranging Hanuman langurs.

Ovarian cycles in catarrhine primates are uniquely characterized by prolonged periods of sexual activity in which the timings of ovulation and copulation do not necessarily correspond. According to current hypotheses of primate social evolution, extended sexuality in multi-male groups might represent part of a female strategy to confuse paternity in order to reduce the risk of infanticide by males. We test this hypothesis by examining mating behaviour in relation to timing of ovulation and paternity outcome in a multi-male group of free-living Hanuman langurs. Using faecal progestogen measurements, we first document that female langurs have extended receptive periods in which the timing of ovulation is highly variable. Next, we demonstrate the capacity for paternity confusion by showing that ovulation is concealed from males and that copulations progressively decline throughout the receptive phase. Finally, we demonstrate multiple paternity, and show that despite a high degree of monopolization of receptive females by the dominant male, non-dominant males father a substantial proportion of offspring. We believe that this is the first direct evidence that extended periods of sexual activity in catarrhine primates may have evolved as a female strategy to confuse paternity.

Animals↗

Calculations of properties of screened He-like systems using correlated wave functions.

The purpose of the present study is twofold. First, the techniques of correlated wave functions for two-electron systems have been extended to obtain results for P and D states in a screening environment, and in particular for Debye screening. In these calculations, the satisfaction of both the quantum virial theorem and a related sum rule has been enforced and found to provide a high degree of stability of the solutions. Second, in order to facilitate the general use of correlated wave functions in combination with sum rule stability criteria, a rather systematic computational approach to this notoriously cumbersome method has been developed and thoroughly discussed here. Accurate calculations for few-electron systems are of interest to plasma diagnostics; in particular, when inaccuracies in binding energies are drastically magnified as they occur in exponents of Boltzmann factors.

Journal Article↗

Plasma antioxidant capacity of HIV-seropositive and healthy subjects during long-term ingestion of fruit juices or a fruit-vegetable-concentrate containing antioxidant polyphenols.

OBJECTIVE: To investigate whether antioxidant polyphenols from fruit juices or a fruit-vegetable-concentrate increase the plasma antioxidant capacity in HIV-infected and healthy subjects. DESIGN: Twenty-three HIV-seropositive and 18 seronegative adults were randomized to ingest either 1 l of fruit juice or 30 ml fruit-vegetable-concentrate per day over 16 weeks in addition to their normal Western diet. METHODS: Plasma antioxidant capacity was determined as Trolox equivalent antioxidant capacity (TEAC) at baseline, after 1 and 16 weeks of intervention, and after a 6 week washout. RESULTS: There was no difference in plasma antioxidant capacity between HIV-infected and healthy subjects at baseline (P=0.1). After 16 weeks of intervention TEAC increased in HIV-positive subjects with both types of polyphenol supplementation (juice, 1.38+/-0.07 to 1.42+/-0.04 mM, P=0.034; concentrate, 1.40+/-0.09 to 1.46+/-0.08 mM, P=0.025). TEAC was not altered by either type of supplementation in HIV-seronegative subjects. CONCLUSION: Plasma antioxidant capacity can be increased by long-term ingestion of polyphenols from fruit juices or fruit-vegetable-concentrate in HIV-seropositive but not in HIV-seronegative subjects. SPONSORSHIP: This study was supported by a grant and Cellagon aurum from HG Berner GmbH, Altenholz, and fruit juices from Eckes Granini GmbH & Co. KG, Nieder-Olm.

Adult↗

Functional MRI in a 6-year-old boy with unilateral cortical malformation: concordant representation of both hands in the unaffected hemisphere.

Functional magnetic resonance imaging (fMRI) was performed in a 6-year-old boy with a complex malformation of the right hemisphere who suffered from pharmaco-refractory epilepsy. Clinical examination revealed left-sided hemiparesis and marked mirror movements of the opposite hand both during paretic and non-paretic hand movements. Functional MRI of repetitive unimanual grasping demonstrated that the two hands share a common cortical representation located in the central motor region of the unaffected left hemisphere. The affected right hemisphere did not show any activation during either task. This case study demonstrates the feasibility and usefulness of motor fMRI in young children before they undergo epilepsy surgery.

Brain Mapping↗

Effects of lithium on thrombopoiesis in patients with low platelet cell counts following chemotherapy or radiotherapy.

Therapy for neoplasma is limited by hematological side effects of tumor-destructive therapy and, in part, makes expensive supportive care necessary to overcome and treat leukopenia and thrombocytopenia and their consequences. Thrombocytopenia is a major clinical problem caused by chemotherapy and radiotherapy. An effective and very cost-effective option for treating moderate neutropenia is the administration of lithium carbonate. Lithium induces the release of colony-stimulating factors (CSF) and therefore stimulates proliferation of neutrophil granulocytes. Other cytokines, such as interleukin-1 (IL-1), IL-6, and tumor-necrosis factor-alpha (TNF-alpha), are also stimulated. Apart from granulocyte-macrophage-CSF (GM-CSF), there have as yet been no reports of lithium salts inducing early activating factors for the megakaryocytic lineage, such as IL-3, IL-11, stem cell factor and flt-3 ligand, or maturation factors, such as thrombopoietin (TPO). A statistically significant increase in the mean number of platelets for patients with cell counts below 150,000/microL on the commencement of treatment with lithium carbonate could be observed. Patient tolerability of lithium carbonate therapy is very good. Patients with persistent leukopenia and thrombocytopenia following chemotherapy or radiotherapy can be treated with this trace element very cost-effectively. Unfortunately this treatment has not gained acceptance in clinical oncology in the face of extremely cost-intensive treatment with recombinant GM-CSF, IL-11 or, potentially, thrombopoietin.

Adult↗

Hormonal correlates of reproductive seasonality in wild female hanuman langurs (Presbytis entellus).

To date, it is not known whether the seasonal occurrence of sexual behavior and mating in free-ranging Hanuman langurs at Ramnagar, Nepal, is correlated with seasonal changes in female ovarian function, and, if so, which factor(s) triggers the onset of the reproductive period. Using noninvasive fecal hormone analysis in combination with behavioral observations, this study was carried out to: 1) investigate and characterize seasonal patterns of ovarian cyclicity and timing of conception in wild langur females living in a highly seasonal habitat; and 2) examine the relationship between seasonal patterns of ovarian cyclicity, behavioral estrus, and female physical condition. Behavioral data and fecal samples were collected during a total period of 14 months from nine females living in a multi-male group. Physical condition of the females was assessed monthly by visual inspection, using a seven-fold scale. Ovulatory cycles and timing of conceptions were identified by the measurement of immunoreactive pregnanediol glucuronide (iPdG) in extracted feces. Hormone profiles in individual females revealed a clearly seasonal distribution in the occurrence of ovulatory cycles, which were restricted to the period from July to October. The distribution of female estrus behavior showed a similar seasonal pattern, and in total 88.2% of all estrus periods observed in the focal females were accompanied by ovulation. Onset of ovarian cycles as well as mating activities were strongly correlated with the onset of the rainy season. Females conceived, on average, in their second ovulatory cycle (pregnancy length: 211.6 +/- 3.4 days), with timing of conception being confined to the months when animals showed an improved physical condition. Collectively the present data clearly suggest that in seasonally-breeding langurs at Ramnagar, ecological conditions (rainfall, food availability, and quality) influence the onset of ovulations and timing of conceptions.

Animals↗

Different effects of bone morphogenetic proteins 2, 4, 12, and 13 on the expression of cartilage and bone markers in the MC615 chondrocyte cell line.

In order to study the lineage leading to chondrocyte and osteoblast phenotype in vertebrate development, we examined the effect of recombinant human bone morphogenetic protein (BMP)-2, BMP-4, BMP-12 [or growth and differentiation factor (GDF)-7], and BMP-13 (or GDF-6) on the phenotypic expression of the mouse chondrocyte cell line MC615, grown for 1 or 2 weeks in monolayer. Protein synthesis rates were monitored after incubation with [(14)C]proline. BMP-2 and BMP-4 increased protein synthesis, in agreement with our observation by phase-contrast microscopy of a highly refractile matrix around MC615 cells treated with BMP-2 and -4. Markers of the chondrocytic and osteoblastic differentiation were analyzed at mRNA level. Expression of the type II collagen gene, a marker of the cartilage phenotype, was up-regulated in the presence of low concentration of BMP-2 or -4 (50 ng/ml) and down-regulated at higher concentrations (100-400 ng/ml). In parallel, this expression was stable in the presence of BMP-12 or -13 in the dose range tested (50-400 ng/ml). Expression of the matrix Gla protein (MGP) gene, another marker of cartilage, was also reduced in the presence of 100 ng/ml BMP-2 or -4, while it remained stable in the presence of BMP-12 or -13 at the same concentration. In contrast, expression of the bone Gla protein (BGP) gene, or osteocalcin, a marker of the bone phenotype, was induced when the cells were treated with BMP-2 or -4 but was not detected when the cells were treated with BMP-12 or -13. At the same time, BMP-2 or -4 markedly up-regulated expression of type X collagen mRNA, indicating that MC615 cells possess the ability to express traits associated with endochondral ossification, when exposed to specific BMPs. Furthermore, detailed analysis of type II collagen expression showed that the alternatively spliced transcript collagen IIB, specific for cartilage, is expressed concomitantly with BGP. Therefore, MC615 chondrocytes can simultaneously express chondrocytic and osteoblastic markers, in response to BMP-2 or -4, but show minimal response to BMP-12 (or GDF-7) or to BMP-13 (or GDF-6). These results raise the possibility that chondrocytes in vivo can express osteoblastic properties, provided they are induced by BMP-2 or -4.

Animals↗

DNA analyses support the hypothesis that infanticide is adaptive in langur monkeys.

Although the killing of dependent infants by adult males is a widespread phenomenon among primates, its causes and consequences still remain hotly debated. According to the sexual selection hypothesis, infanticidal males will gain a reproductive advantage provided that only unrelated infants are killed and that the males increase their chances of siring the next infants. Alternatively, the social pathology hypothesis interprets infanticide as a result of crowded living conditions and, thus, as not providing any advantage. Based on DNA analyses of wild Hanuman langurs (Presbytis entellus) we present the first evidence that male attackers were not related to their infant victims. Furthermore, in all cases the presumed killers were the likely fathers of the subsequent infants. Our data, therefore, strongly support the sexual selection hypothesis interpreting infanticide as an evolved, adaptive male reproductive tactic.

Adaptation, Biological↗

18F-FDG PET studies in patients with extratemporal and temporal epilepsy: evaluation of an observer-independent analysis.

UNLABELLED: The aim of this study was to evaluate an observer-independent analysis of 18F-fluorodeoxyglucose (FDG) PET studies in patients with temporal or extratemporal epilepsy. METHODS: Twenty-seven patients with temporal epilepsy and 22 patients with extratemporal epilepsy were included in the study. All patients with temporal epilepsy and 7 patients with extratemporal epilepsy underwent surgical treatment. In patients who showed significant postoperative improvement (temporal, n = 23; extratemporal, n = 6), the epileptogenic focus was assumed to be located in the area of surgical resection. In extratemporal epilepsy patients who did not undergo surgery, the focus localization was determined using a combination of semiology, ictal and interictal electroencephalography, [99mTc]ethyl cysteinate dimer SPECT, MRI and [11C]flumazenil PET. Visual analysis was performed by two experienced and two less experienced blinded observers using sagittal, axial and coronal images. In the automated analysis after anatomic standardization and generation of three-dimensional stereotactic surface projections (SSPs), a pixelwise comparison of 18F-FDG uptake with an age-matched reference database (n = 20) was performed, resulting in z score images. Pixels with the maximum deviation were detected, summarized and attached to one of 20 predefined surface regions of interest. For comparison with 18F-FDG PET and MR images, three-dimensional overlay images were generated. RESULTS: In patients with temporal epilepsy, the sensitivity was comparable for visual and observer-independent analysis (three-dimensional SSP 86%, experienced observers 86%-90%, less experienced observers 77%-86%). In patients with extratemporal epilepsy, three-dimensional SSP showed a significantly higher sensitivity in detecting the epileptogenic focus (67%) than did visual analysis (experienced 33%-38%, each less experienced 19%). In temporal lobe epilepsy, there was moderate to good agreement between the localization found with three-dimensional SSP and the different observers. In patients with extratemporal epilepsy, there was a high interobserver variability and only a weak agreement between the localization found with three-dimensional SSP and the different observers. Although three-dimensional SSP detected multiple lesions more often than visual analysis, the determination of the highest deviation from the reference database allowed the identification of the epileptogenic focus with a higher accuracy than subjective criteria, especially in extratemporal epilepsy. CONCLUSION: Three-dimensional SSP increases sensitivity and reduces observer variability of the analysis of 18F-FDG PET images in patients with extratemporal epilepsy and is, therefore, a useful tool in the evaluation of this patient group. The benefit of this analytical approach in patients with temporal epilepsy is less apparent.

Adolescent↗

Amplification of microsatellites adapted from human systems in faecal DNA of wild Hanuman langurs (Presbytis entellus).

Microsatellite systems originally established for human DNA were utilized for paternity testing from faecal DNA in a natural population of Hanuman langurs (Presbytis entellus). Thirty-two primer pairs were applied to amplify DNA obtained from langur faeces. Twenty-two of these primer pairs yielded specific amplification products and 11 loci were polymorphic. Allele distributions and heterozygosity rates were determined for five systems. Genetic information from these five systems was sufficient for paternity exclusion in 46 out of 52 cases. Results were consistent enough to allow genotyping from faeces, although sometimes only one allele was amplified in a heterozygous individual. In conclusion, relationship analyses from faeces are possible in spite of the evolutionary distance between humans and langurs.

Animals↗