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Biomedical subjects

A Wolf

Publications and source records attributed to A Wolf.

At least 73 records · Page 4Linked to original sources

Social phobia in spasmodic torticollis.

OBJECTIVES: To study the prevalence of psychiatric comorbidity assessed by the use of a structured clinical interview in a large, representative sample of patients with spasmodic torticollis (ST) and to test the hypothesis that social phobia would be highly prevalent. METHODS: In a consecutive cohort of 116 patients with ST treated with botulinum toxin overall psychiatric comorbidity was studied prospectively with the structured clinical interview (SCID) for DSM-IV axis I disorders. Physical disability and psychosocial variables were also assessed with standardised self rating questionnaires. RESULTS: 41.3% of the subjects met DSM-IV clinical criteria A-G for current social phobia as the primary psychiatric diagnosis. This figure rose to 56% including secondary and tertiary psychiatric diagnosis. There was no correlation between severity of disease (Tsui score, severity of pain, body image dissatisfaction score) and psychiatric comorbidity. The only significant predictor of psychiatric comorbidity was depressive coping behaviour (logistic regression analysis, p < 0.01; OR=10.8). Compared with a representative sample of the general adult population, in the patients with ST the prevalence of clinically relevant social phobia is 10-fold, of mood disorders 2.4-fold, and of lifetime psychiatric comorbidity 2.6-fold increased. CONCLUSIONS: A particularly high prevalence of social phobia was found in the cohort of patients with ST. The finding of a high prevalence of social phobia and depressive coping behaviour as the main predictor of psychiatric comorbidity may make a subgroup of patients with ST particularly amenable to specific psychotherapeutic interventions.

Adaptation, Psychological↗

[Efficient use of sleep pillows in patients suffering from non-organic sleep disorders--a pilot study].

OBJECTIVE: Sleep disorders may critically affect working performance and quality of life. Sleep pillows have been traditionally used to overcome such disorders. Scientifically based clinical trials to demonstrate the efficacy are missing. METHODS: 28 patients with problems falling asleep and/or staying asleep not related to psychiatric or organic diseases were investigated in an accredited sleep laboratory. The diagnosis was confirmed by polysomnography. After 2 and 4 weeks of treatment the polysomnography was repeated to document any influences by the sleep pillows. RESULTS: The polysomnographic records showed a monotonic trend to regain an age-related distribution of the non-REM sleep stages. The REM sleep phase increased nearly twofold; however, the norm values were not reached within the 4-week period of treatment. Sleep pillows of intensity 2 were superior to those of intensity 1; a further increase to intensity 3 did not create any additional effect. CONCLUSION: The results demonstrate an effective treatment of non-complicated sleep disorders with sleep pillows, which has been shown with objective measurements in a sleep laboratory.

Aromatherapy↗

Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability.

BACKGROUND: Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS) but the evolution over time and the relationship to clinical characteristics are not yet established. OBJECTIVES: We investigated the correlation of disease activity and progression of disability with composite scores of cardiovascular autonomic dysfunction and serum levels of catecholamines in a cross-sectional study of patients with clinically active and clinically stable MS. In a longitudinal study of clinically active MS patients, we performed cardiovascular reflex tests for up to 2 years. METHODS: Twenty-six patients with clinically active relapsing-remitting MS, age 33.0 +/- 7.3 years, and nine patients with clinically stable MS, age 41.3 +/- 10.9 were studied. Twenty-four healthy volunteers served as controls. Standard autonomic tests were repeated at 3, 6, 12, 18 and 24 months in 18 of the 26 active patients participating in a placebo-controlled trial with interferon-beta-1a. Parasympathetic dysfunction was assessed by heart rate response to the Valsalva manoeuvre, deep breathing and active change of posture, while sympathetic dysfunction was analysed by blood pressure response to active change of posture and to sustained handgrip, and by measuring levels of norepinephrine and epinephrine in serum obtained in the supine position. RESULTS: In the cross-sectional study, the number of patients with at least one abnormal sympathetic test was higher in the 'active' patient group (39%) than in healthy controls (8%, P< 0.02) or 'stable' patients (0%, P< 0.04), while no difference was seen in the parasympathetic score. Median catecholamine levels were significantly lower in 'active' MS patients than in those with stable disease (norepinephrine, 204 ng/l (interquartile range 158-310 ng/l) vs 363 ng/l (269-507 ng/l), P<0.02 and epinephrine, 23 ng/l (16-28 ng/l) vs 32 ng/l (24-107 ng/l), P<0.04). In the subgroup of patients studied longitudinally, parasympathetic but not sympathetic dysfunction increased slightly during the follow-up period, with a significant correlation to the increase in clinical disability (r=0.7, P<0.002). No difference was seen for any of the autonomic scores between patients treated with interferon-beta (n=12) and those receiving placebo (n=6). During acute exacerbations, only parasympathetic dysfunction tended to increase in parallel with a deterioration in the EDSS. CONCLUSIONS: Parasympathetic dysfunction was closely related to the progression of disability in patients with MS. In contrast, sympathetic dysfunction was associated to the clinical activity of MS. This is in line with previous observations suggesting that the autonomic nervous system may be intimately linked with the disordered immune regulation in MS.

Adjuvants, Immunologic↗

Novel long-acting somatostatin analog with endocrine selectivity: potent suppression of growth hormone but not of insulin.

Somatostatin, also known as somatotropin release-inhibiting factor (SRIF), is a natural cyclic peptide inhibitor of pituitary, pancreatic, and gastrointestinal secretion. Its long-acting analogs are in clinical use for treatment of various endocrine syndromes and gastrointestinal anomalies. These analogs are more potent inhibitors of the endocrine release of GH, glucagon, and insulin than the native SRIF; hence, they do not display considerable physiological selectivity. Our goal was to design effective and physiologically selective SRIF analogs with potential therapeutic value. We employed an integrated approach consisting of screening of backbone cyclic peptide libraries constructed on the basis of molecular modeling of known SRIF agonists and of high throughput receptor binding assays with each of the five cloned human SRIF receptors (hsst1-5). By using this approach, we identified a novel, high affinity, enzymatically stable, and long-acting SRIF analog, PTR-3173, which binds with nanomolar affinity to human SRIF receptors hsst2, hsst4, and hsst5. The hsst5 and the rat sst5 (rsst5) forms have the same nanomolar affinity for this analog. In the human carcinoid-derived cell line BON-1, PTR-3173 inhibits forskolin-stimulated cAMP accumulation as efficiently as the drug octreotide, indicating its agonistic effect in this human cell system. In hormone secretion studies with rats, we found that PTR-3173 is 1000-fold and more than 10,000-fold more potent in inhibiting GH release than glucagon and insulin release, respectively. These results suggest that PTR-3173 is the first highly selective somatostatinergic analog for the in vivo inhibition of GH secretion, with minimal or no effect on glucagon and insulin release, respectively.

Animals↗

School-age children born to diabetic mothers and to mothers with gestational diabetes exhibit a high rate of inattention and fine and gross motor impairment.

OBJECTIVES: To study the neurobehavioral effects that pregestational and gestational diabetes might have on offspring at school age. STUDY DESIGN: We studied neurobehavioral function at school age of 57 children born to 48, well controlled, diabetic mothers and of 32 children born to 32 women with gestational diabetes. Their development was compared with 57 control children matched by age, birth order and parental socio-economic status, using a number of cognitive, behavioral, sensory and motor neurological tests. RESULTS: The IQ scores on the WISC-R and Bender tests of the children born to diabetic mothers were similar to those of control children, but the Bender scores of the children born to mothers with gestational diabetes were slightly lower. No differences were found between the study groups in various sensory-motor functions in comparison to controls. However, both study group children performed less well than controls in fine and gross motor functions as observed on the Bruininks-Oseretzki test of motor proficiency. The scores of children born to the mothers with pregestational diabetes were higher than controls on the Touwen & Prechtl neurological examination (worse function). The children from both research groups also performed worse on the Pollack taper test that is designed to detect inattention and hyperactivity. The children of the two study groups also had slightly higher scores on the Conners abbreviated parents-teachers questionnaire measuring hyperactivity and inattention, but the differences from controls were not statistically significant. We found a negative correlation between the performance of the children born to mothers with pregestational diabetes on various neurodevelopmental and behavioral tests and the severity of maternal hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria. CONCLUSIONS: Pregestational or gestational diabetes was found to adversely affect attention span and motor functions of offspring at school age, but not their cognitive ability. These effects were negatively correlated with the degree of maternal glycemic control, and were more pronounced in younger children.

Adult↗

Study of charmless hadronic B meson decays to pseudoscalar-vector final states.

We report results of searches for charmless hadronic B meson decays to pseudoscalar( pi(+/-), K+/-, pi(0), or K(0)(S))-vector( rho, K(*), or omega) final states. By using 9.7x10(6) BB pairs collected with the CLEO detector, we report the first observation of B(-)--->pi(-)rho(0), B(0)-->pi(+/-)rho(-/+), and B(-)-->pi(-)omega, which are expected to be dominated by hadronic b-->u transitions. The measured branching fractions are (10.4(+3.3)(-3.4)+/-2.1)x10(-6), (27.6(+8.4)(-7.4)+/-4.2)x10(-6), and (11.3(+3.3)(-2.9)+/-1. 4)x10(-6), respectively. Branching fraction upper limits are set for all of the other decay modes investigated.

Journal Article↗

Effect of a fixed valerian-Hop extract combination (Ze 91019) on sleep polygraphy in patients with non-organic insomnia: a pilot study.

A pilot study with a fixed extract combination Ze 91019 of valerian and hop was conducted in 30 patients suffering from mild-moderate, non-organic insomnia. The diagnosis was confirmed by polysomnographic standard examinations. The patients were treated with 2 tablets in the evening. Each tablet contains 250 mg valerian extract and 60 mg hop extract. A polysomnographic re-examination after 2 weeks of treatment revealed declines in the sleep latency and the wake time. As a consequence the sleep efficiency increased. Sleep stage 1 (S1) was reduced and the slow wave sleep increased. In addition, the patients judged their being refreshed in the morning by assigning a rating of 1 to 6. They reported an improvement after 2 weeks of treatment. No adverse events were observed. Based on these findings a pivotal study can be designed.

Administration, Oral↗

Germline alterations in the cyclooxygenase-2 gene are not associated with the development of extracolonic manifestations in a large swiss familial adenomatous polyposis kindred.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition leading to the development of multiple colorectal polyps and other features. Intrafamilial variation in phenotype is known to occur in FAP; despite carrying the same causing mutation in the APC gene, disease expression may considerably differ in affected individuals, likely due to the existence of modifier genes. Several lines of evidence suggest the cyclooxygenase-2 (COX-2) gene to be a candidate modifier in FAP. Since COX-2 appears to be expressed in tissues prone to be affected in FAP, it might influence the occurrence of extracolonic manifestations in this disorder. Herein, we investigated whether alterations in the COX-2 gene are involved in the development of extracolonic polyps and extragastrointestinal features. Mutational analysis using single-strand conformation polymorphism (SSCP) in 130 members of a FAP family displaying strong phenotype variation revealed 3 polymorphic sites within the coding region of the COX-2 gene. None of these allelic variants, however, segregated with a particular disease phenotype. In addition, expression analysis was performed in 31 family members with representative phenotypes. Neither of the two polymorphisms detected within the COX-2 promoter was associated with a given phenotype nor was there a significant difference in quality or quantity of COX-2 mRNA in lymphocytes as measured by reverse transcription- and real time quantitative reverse transcription PCR (RT-PCR and TaqMan). In conclusion, germline alterations in the COX-2 gene are unlikely to account for the development of extracolonic disease in FAP patients.

Adenomatous Polyposis Coli↗

Observation of B --> K(+/-) pi(0) and B --> (K)0 pi(0), and evidence for B --> pi(+)pi(-).

We have studied charmless hadronic decays of B mesons into two-body final states with kaons and pions and observe three new processes with the following branching fractions: beta(B-->pi(+)pi(-)) = (4.3(+1. 6)(-1.4)+/-0.5)x10(-6), beta(B-->K(0)pi(0)) = (14.6(+5.9+2.4)(-5.1-3. 3))x10(-6), and beta(B-->K(+)/-pi(0)) = (11.6(+3.0+1.4)(-2.7-1.3))x10(-6). We also update our previous measurements for the decays B-->K(+)/-pi(-/+) and B+/--->K(0)pi(+/-).

Journal Article↗

Two-body B meson decays to eta and eta('): observation of B --> eta K*.

In a sample of 19 x 10(6) produced B mesons, we have observed the decays B-->eta K(*) and improved our previous measurements of B-->eta'K. The branching fractions we measure for these decay modes are B(B+-->eta K(*+)) = (26.4(+9.6)(-8.2)+/-3.3)x10(-6), B(B(0)-->eta K(*0)) = (13.8(+5.5)(-4.6)+/-1.6)x10(-6), B(B(+)-->eta'K(+) = (80(+10)(-9)+/-7)x10(-6), and B(B(0)-->eta'K0) = (89(+18)(-16)+/-9)x10(-6). We have searched with comparable sensitivity for related decays and report upper limits for these branching fractions.

Journal Article↗

Measurement of charge asymmetries in charmless hadronic B meson decays.

We search for CP-violating charge asymmetries (alpha(CP)) in the B meson decays to K(+/-)pi(-/+), K(+/-)pi(0), K(0)(S)pi(+/-), K(+/-)eta('), and omega pi(+/-). Using 9.66 million upsilon(4S) decays collected with the CLEO detector, the statistical precision on alpha(CP) is in the range of +/-0.12 to +/-0.25 depending on decay mode. While CP-violating asymmetries of up to +/-0.5 are possible within the standard model, the measured asymmetries are consistent with zero in all five decay modes studied.

Journal Article↗

Strategies to antagonise the cyclosporine A-induced proliferation of human pulmonary artery smooth muscle cells: anti-endothelin-1 antibodies, verapamil, and octreotide.

The present study investigated the mechanisms mediating the actions of the immunosuppressive drug cyclosporine A (CsA) on human pulmonary artery smooth muscle cell (PASMC) proliferation. The new hydroxyethyl derivative of D-serine(8)-cyclosporine, SDZ IMM 125, was used for comparison. CsA-induced proliferation was determined by incorporation of [(3)H]thymidine ([(3)H]Thy). CsA in the concentration range between 0.1 nM and 0.1 microM induced a concentration-dependent increase in proliferation after 24, 48, and 72 hr of incubation. Higher CsA concentrations were cytotoxic. When proliferation experiments were performed in the presence of a monoclonal antibody against endothelin-1 (ET-1), CsA-induced proliferation was totally inhibited. No inhibition occurred in the presence of the same antibody when heat-inactivated or a non-specific monoclonal antibody. In parallel, CsA increased the production of ET-1, as determined by radioimmunoassay. Incubation of PASMCs with ET-1 at the concentration range at which the latter was released by CsA induced cell proliferation. The somatostatin derivative Sandostatin (SDT; octreotide), which is an inhibitor of the growth of smooth muscle cells as well as a potent inhibitor of ET-1 secretion, inhibited both the CsA-induced ET-1 release and the increase in [3H]Thy incorporation by PASMCs. A similar effect was observed for the calcium channel blocker verapamil (VP). SDZ IMM 125 induced weaker effects than CsA in terms of PASMC proliferation and ET-1 secretion. In conclusion, CsA increased the rate of proliferation of PASMCs, while SDZ IMM 125 induced a weaker effect. Anti-ET-1 antibody, VP, and SDT significantly inhibited CsA-induced PASMC proliferation.

Antibodies↗

Influence of magnetic fields on electron-Ion recombination at very low energies

Radiative recombination (inverse photoionization) is believed to be well understood since the beginning of quantum mechanics. Still, modern experiments consistently reveal excess recombination rates at very low electron-ion center-of-mass energies. In a detailed study on recombination of F6+ and C6+ ions with magnetically guided electrons we explored the yet unexplained rate enhancement, its dependence on the magnetic field B, the electron density n(e), and the beam temperatures T( perpendicular) and T( ||). The excess scales as T(-1/2)( perpendicular) and, surprisingly, as T(-1/2)( ||), increases strongly with B, and is insensitive to n(e). This puts strong constraints on explanations of the enhancement.

Journal Article↗

Mechanisms of cyclosporine A-induced apoptosis in rat hepatocyte primary cultures.

In rat hepatocytes and isolated liver mitochondrial fractions, Cyclosporine A (CsA) is often used as a specific inhibitor of mitochondrial Ca(2+) release and as a specific blocker of mitochondrial membrane potential and permeability transition (MPT), which are all processes involved in the inhibition of apoptosis. However, neither inhibition nor induction of apoptosis by CsA has yet been described in the rat hepatocyte primary culture during incubation for 4 and 20 h. It was the purpose of the present study to examine by means of morphological and biochemical criteria the effects of CsA on apoptosis and to characterize the underlying mechanisms. Rat hepatocytes were cultured for 4 or 20 h with CsA at concentrations of 0, 10, 25, and 50 microM. Chromatin condensation and fragmentation, DNA fragmentation (TUNEL), membrane phosphatidylserine distribution (Annexin V), caspase-1, -3, and -6 activity, mitochondrial membrane potential (Rhodamine 123), and cytochrome c release into the cytosol were investigated. Four hours after CsA treatment, chromatin condensation and fragmentation and the number of TUNEL- and Annexin V-positive cells increased dose-dependently without any observable enzyme leakage, which indicated the integrity of the outer cell membrane. After 20 h of CsA incubation apoptosis parameters were further increased and were accompanied by the increased activity of the cysteine protease, caspase-3 (CPP 32), and slightly increased caspase-6 (Mch 2), but not caspase-1 (ICE). The caspase-3 inhibitor, Ac-DEVD-CHO, inhibited caspase-3 activation and attenuated CsA-induced apoptosis and LDH leakage. The caspase-6 inhibitor, Ac-VEID-CHO, only marginally inhibited CsA-induced apoptosis. Decreased mitochondrial membrane potential and cytochrome c release went in parallel with ultrastructural mitochondrial changes and might be regarded as early events that trigger the apoptosis cascade. Transmission electron microscopy confirmed an increase in the number of necrotic cells after 20 h, but not after 4 h, compared with controls.

Animals↗

A conical slit for three-dimensional XRD mapping.

Traditionally, depth resolution in diffraction experiments is obtained by inserting pinholes in both the incoming and diffracted beam. For materials science investigations of local strain and texture properties this leads to very slow data-acquisition rates, especially when characterization is performed on the level of the individual grains. To circumvent this problem a conical slit has been manufactured by wire-electrodischarge machining. The conical slit has six 25 microm-thick conically shaped openings matching six of the Debye-Scherrer cones from a face-centred-cubic powder. By combining the slit with a microfocused incoming beam of hard X-rays, an embedded gauge volume is defined. Using a two-dimensional detector, fast and complete information can be obtained regarding the texture and strain properties of the material within this particular gauge volume. The average machining and assemblage errors of the conical slit are found both to be of the order of 5 microm. An algorithm for alignment of the slit is established, and the potential of the technique is illustrated with an example of grain mapping in a 4.5 mm-thick Cu sample.

Journal Article↗

Effect of exercise on coronary endothelial function in patients with coronary artery disease.

BACKGROUND: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. METHODS: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. RESULTS: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). CONCLUSIONS: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.

Acetylcholine↗

Observation of radiative leptonic decay of the tau lepton

Using 4.68 fb(-1) of e(+)e(-) annihilation data collected with the CLEO II detector at the Cornell Electron Storage Ring, we have studied tau radiative decays tau(-)-->nu(tau)&mgr;(-)nu;(&mgr;)gamma and tau(-)-->nu(tau)e(-)nu;(e)gamma. For a 10 MeV minimum photon energy in the tau rest frame, the branching fraction for radiative tau decay to a muon or electron is measured to be (3.61+/-0.16+/-0. 35)x10(-3) or (1.75+/-0.06+/-0.17)x10(-2), respectively. The branching fractions are in agreement with standard model theoretical predictions.

Journal Article↗

[Clinical comparison of a digital with an analog hearing aid].

The benefit of innovative hearing aid technology can be evaluated in clinical trials. The present study describes the comparison of a new digital hearing aid with an analogue device serving as a reference. The tests were carried out with 15 experienced hearing aid wearers. To prevent the influence of different fitting algorithms such as prescriptive or loudness-based the digital devices were not renewed fitted but their level- and frequency-depending gain was adjusted to that of the reference. Different tests concerning loudness perception (category loudness scaling) speech discrimination in noise (the Göttingen sentence test) and self-assessment of the benefit by questionnaires were performed. All tests yielded slightly better results for the digital hearing aid. The speech audiometric evaluation showed somewhat better discrimination for the test-device. The questionnaires yielded a marked preference for the digital device. Because the study was not blinded influences due to the knowledge of the subjects of testing a new technology generally can occur. On the other hand, the question arises whether present audiometric tests sufficiently consider signal processing of modern hearing systems. Furthermore, one has to take into account that only a few of the features of digital technology such as noise-reduction and feedback-cancellation were considered in this study to allow for a sensible comparison. Because of the large number of possibilities offered by digital technology additional benefit by the hearing aid can be expected.

Analog-Digital Conversion↗