FGF23-klotho axis, bone fractures, and arterial stiffness in dialysis: a case-control study.

We performed a case-control study on 130 age- and sex-matched hemodialysis patients. In multivariate analysis, we observed that FGF23 levels were associated with fracture incidence and that soluble α-klotho levels were associated with the aortic-brachial arterial stiffness ratio. INTRODUCTION: New bone markers such as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23), and α-klotho have been identified as potential key players in bone and vascular abnormalities of chronic kidney disease. Therefore, we aimed to assess whether these markers are associated with fractures, bone metabolism, and vascular stiffness in dialysis patients. METHODS: In a prospective hemodialysis cohort, where plasma samples and vascular assessment were performed at baseline, we matched patients who experienced a fracture during follow-up with sex- and age-matched non-fractured patients on a 1:4 ratio. Sclerostin, DKK1, α-klotho, FGF23, and markers of bone formation (alkaline phosphatase and procollagen type 1-N terminal propeptide [P1NP]) and bone resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) were measured in baseline plasma samples. Aortic-brachial pulse wave velocity ratio, a blood pressure independent measure of arterial stiffness, was used to assess vascular stiffness at baseline. RESULTS: We included 130 hemodialysis patients (26 fractured, 104 non-fractured) with a median follow-up of 42 months and a median age of 72 years. In multivariate Cox regression models, high FGF23 levels were associated with increased fracture incidence (adjusted HR = 2.97; 95% CI 1.18, 7.43). α-Klotho levels were associated with bone formation but not resorption markers. In both univariate and multivariable adjusted models, α-klotho levels were inversely associated with the aortic-brachial pulse wave velocity ratio (ß = - 0.070; 95% CI - 0.133, - 0.006). CONCLUSIONS: These results suggest a role for FGF23/klotho axis on bone and vascular metabolism in dialysis populations.

[Health and Prevention Behaviour of Persons with and without Migration Background]. / Gesundheits- und Präventionsverhalten von Personen mit und ohne Migrationshintergrund.

Based on a sample of the Hannover registration office this project analyses the health and prevention behaviour of Russian- and Turkish-language migrants compared to natives. The project analysis revealed considerable differences, particularly concerning addiction behaviour and physical activities.

[Social medicine in medical faculties: realisation of the topic in the specialty "social medicine, occupational health"]. / Sozialmedizin an medizinischen Fakultäten: Realisierung des Teilbereichs im Fach "Sozialmedizin, Arbeitsmedizin".

PURPOSE OF THE STUDY: The 9 (th) Revision of German Medical Licensing Regulations for Physicians has come into effect on October 1 (st) 2003. Social medicine was separated into the fields ""occupational health, social medicine" and the various cross-sectional modules: epidemiology, biometry, medical computer science; health economics, health-care system, public health; prevention, health promotion; rehabilitation, physical medicine, naturopathic treatment. This paper studies the realisation of teaching in the field social medicine at German medical faculties. METHODS: The survey was conducted in collaboration with the German Association for Social Medicine and Prevention (DGSMP). A survey was conducted at 38 institutes of 36 German medical faculties. The written questionnaire contained mostly selection items in which chances and barriers of the field were queried with supply items. Information about time scale, general conditions and resources was aked for. On the basis of the guidelines of the DGSMP, the topics to be taught were evaluated concerning their relevance and integration into education. RESULTS: The response rate was 68% (n=26). Social insurance, basic principles, responsibility in the Social Security Code and the different providers were judged as the most important topics. There was a strong demand for lecturing material. 82% (n=18) of the faculties wished to have specific material, for example e-learning, examples, lesson plans, curricula and also textbooks. 91% (n=19) of the faculties requested an exchange of information between the faculties concerning educational contents, motivation of students and e-learning. DISCUSSION: The realisation of teaching is different between the faculties concerning the number of hours, teaching methods and number of students per year. The motivation of the students is one of the problems, but also the lack of acceptance within the clinic. Specific resources and exchange between the faculties are necessary concerning e-learning, which is offered at only few faculties so far, but interest for a more intensive usage exists. Potentials of social medicine are the promotion of awareness among the students and the "identification of basics for medical acts in the social security system". Social medicine offers the possibility to connect the theoretical institutes with the clinic.

["Responsiveness" in psychiatric outpatient care and in hostel management]. / "Responsiveness" in der psychiatrischen ambulanten Versorgung und in der Heimversorgung.

OBJECTIVE: Responsiveness is a concept developed by the World Health Organisation (WHO) to evaluate health system performance. It measures how well a health system meets its users' legitimate expectations in non-medical related service aspects. Responsiveness consists of the categories "patient orientation" and "respect for persons". It is operationalised by nine (8+1) domains. This project aims to explore the responsiveness concept as a possibility to evaluate the performance of mental health care. METHOD: Face to face interviews with users of outpatient and hostel mental health services by means of a standardised instrument, developed by WHO were carried out. RESULTS: Overall responsiveness in outpatient care was rated by a lower proportion of users negative than responsiveness in hostel care (15 vs. 20%). Socio-demographic characteristics were related only to responsiveness ratings in hostel care when legal guardianship was considered. Domains indicated as most important (attention, participation) in out-patient care did not perform well there. In hostel care the domains attention and respect were rated as most important. These domains performed well. DISCUSSION AND CONCLUSIONS: The results are in line with the literature and adequately reflect the realities in mental health care. The responsiveness concept offers a systematic approach for considering the categories "patient orientation" and "respect for persons" as quality criteria in mental health care. Evaluating mental health service provision using the concept of responsiveness, indicates where to launch reforms in health care.

[Framework of palliative care in Germany and development of public health targets. Study design and methods]. / Rahmenbedingungen für die palliative Versorgung in Deutschland und Entwicklung von Public-Health-Zielen. Studiendesign und Methodik.

To provide adequate end-of-life care is a substantial task of the health care system. However, it has been largely disregarded. For public health research, important activities include analysing the societal requirements as well as the health system-related possibilities and framework. Therefore, a study, funded by the German Research Foundation, for the first time (1) examines the viewpoints of a wide range of stakeholders that operate on different levels of the German health system, and (2) develops broadly based public health targets for palliative care in Germany. This article presents the conceptual framework, design and methods of the study.

[Implementation of the 9th revision of medical licensing regulation for physicians in the cross-sectional area "prevention and health promotion" at the German medical faculties]. / Umsetzung der 9. Arztlichen Approbationsordnung im Querschnittsbereich "Prävention und Gesundheitsförderung" an den medizinischen Fakultäten in Deutschland.

The coming into effect of the 9th Revision of German Medical Licensing Regulations for Physicians on October 1st 2003 saw prevention and health promotion become a cross-sectional module of medical training subject to compulsory assessments and a grading system. The individual medical faculties are responsible for content and teaching methods. An initial survey of all 36 German medical facilities shows the current implementation of the new cross-sectional area. In a partly standardised questionnaire these faculties were surveyed on the linking of coordination and realisation, the didactic methodology concept of teaching as well as potentials and difficulties in implementation. The implementation of the cross-sectional area differs in responsibility with regard to coordination and content, time provided, integration of practice in health care and forms of assessment. Whereas consensus exists regarding the relevance and integration of preventive themes in teaching, the picture for health promotion is very heterogeneous.

[Morbidity and health in old age. A challenge for prevention and health care]. / Krankheitslast und Gesundheit im Alter. Herausforderungen für die Prävention und gesundheitliche Versorgung.

Due to chronic illness and multimorbidity, the physical and psychosocial impairments increase significantly in the second half of life. Even though the health condition of the elderly has improved in recent years, the potential for prevention in older people is still undervalued. On the basis of surveys, data from the Association of CHI Physicians and health insurance data, this article provides a review of health and health behaviour of the elderly in Germany. It aims to point out areas of particular relevance for prevention and preventive approaches. Strategies that consider mental and social aspects of aging beside the physical ones are necessary. Systematic, personal and professional factors still inhibit the realisation of these strategies. In this context, doctors and nurses are particularly important as primary professional contact persons for the target group. However, prevention and health promotion in that age group are social tasks, which need the appropriate involvement of further professionals and an explicit political agenda setting.

Continuous-wave operation of a single-frequency optical parametric oscillator at 4-5 microm based on periodically poled LiNbO3.

We present a cw, Nd:YAG-pumped singly resonant single-frequency narrow-linewidth high-power optical parametric oscillator with idler tuning from 3.7 to 4.7 microm. In this spectral range the absorption of the idler wave in the LiNbO3 crystal is significant, causing the oscillation threshold to increase with a subsequent decrease in output power from 1.2 W at 3.9 microm to 120 mW at 4.7 microm. The optical parametric oscillator's cavity was stabilized and mode-hop tuned with a rotatable solid etalon but with a subsequent reduction in idler power of as much as 50%. We demonstrated the usefulness for spectroscopy by recording the photoacoustic spectrum of a strong CO2 absorption, using a 24-GHz continuous idler scan.

Wide single-mode tuning of a 3.0- 3.8-mum, 700-mW, continuous-wave Nd:YAG-pumped optical parametric oscillator based on periodically poled lithium niobate.

A new optical parametric oscillator (OPO) for the mid-infrared wavelength region of 3-3.8mum with an idler output power of up to 1.5 W has been developed. The singly resonant OPO is pumped by a single-mode, 10-W, continuous-wave Nd:YAG laser and consists of a bow-tie ring cavity with a fan-out periodically poled lithium niobate crystal and a low-finesse intracavity air-spaced etalon. The single-frequency idler output can be continuously tuned over 24 GHz with 700-mW power by tuning of the pump laser. The tuning was demonstrated by recording of an absorption line of ethane with photoacoustic spectroscopy.

Difference frequency generation of 8-microm radiation in orientation- patterned GaAs.

First-order quasi-phase-matched difference frequency generation of narrowband tunable mid-infrared light is demonstrated in orientation-patterned GaAs. The all-epitaxial orientation-patterned crystal is fabricated by a combination of molecular beam epitaxy and hydride vapor phase epitaxy. Lasers at 1.3 and 1.55 microm were mixed to give an idler output at 8 microm, with power and wavelength tuning consistent with theoretical estimates, indicating excellent material uniformity over the 19-mm-long and 500-microm-thick device.

Broadly Tunable, Mode-Hop-Tuned cw Optical Parametric Oscillator Based on Periodically Poled Lithium Niobate.

We describe a broadly tunable, cw optical parametric oscillator (OPO) based on periodically poled lithium niobate. The OPO can be tuned over a broad region in the mid IR (2900-3100 cm(-1)) covering the important C-H stretch region while a high spectral resolution (<0.1 cm(-1)) is maintained. The OPO is the light source for a field-portable photoacoustic spectrometer for gas-phase monitoring of volatile organic compounds.

The clinical suitability of laparoscopic instrumentation. A prospective clinical study of function and hygiene.

On the basis of experience gained from 6,000 laparoscopies (73% cholecystectomies) at the Moabit Hospital in Berlin, we carried out a cohort study to analyze the failure rate and decontamination of labeled "tracer" instruments processed in three test trays that were each subjected to 100 cycles. The majority of repairs focused on the functional parts of separable scissors and damaged or lost components. At 4%, the repair index after laparascopic use was less than that of a previously documented investigation period covering 1990 to 1996. A comparison of the costs of disposable and reusable instruments showed that reusable instruments were more cost-effective by a factor of > or =10, indicating that the price gap reported in our previous calculation for 1992 and 1994 has closed only slightly. After 100 cycles, we found traces of proteinaceous material in the eluate on every fourth instrument inspected (eight of 32); half of them (four) gave a positive reading when tested with a hemoglobin pseudoperoxidase test stick. It must be said, however, that similar residual contamination has been found on instruments used in conventional open surgery, with no indication of clinical relevance. This study was designed to examine the clinical suitability of laparoscopic instruments in terms of function and hygiene. Improvements in instrument design and cleanability must focus in particular on the reproducibility of cleaning results, because cleaning is the most important step in processing sterile supplies. As the number of minimally invasive operations has risen considerably, a mere visual check no longer meets the requirements prescribed by modern quality assurance. A multicenter study of residual proteins found on tracer instruments in all surgical fields is now in progress.

Patients with dyspepsia benefit from eradication of Helicobacter pylori if other organic causes for dyspepsia were carefully ruled out.

AIM: In order to investigate the potential of Helicobacter pylori (HP) to induce dyspepsia, we performed a randomized prospective study on the long-term effect of HP-eradication on symptoms of HP-positive dyspeptic patients in whom other organic causes for dyspepsia were carefully ruled out. PATIENTS: 201 patients referred to our endoscopy unit with dyspeptic symptoms for at least six months entered the study. Patients with previous peptic ulcer were excluded. METHODS: After endoscopy of the upper alimentary tract and 13C-urea breath test, patients with active peptic ulcer, hiatal hernia, macroscopic evidence for esophagitis and negative HP-status were excluded. The remaining patients underwent abdominal sonography, H2-exhalation test with lactose, and 24-h pH monitoring in order to exclude other organic causes for dyspepsia. In 20 patients, dyspepsia was assumed to be due to HP-gastritis. Patients received eradication therapy and were controlled as assessed by the 13C-urea breath test six weeks and six months after completion of the therapy. Dyspeptic symptoms were monitored by means of a validated symptom score. RESULTS: Out of 20 patients with HP-gastritis the first eradication treatment was successful in 13, while seven patients remained HP-positive after antibiotic treatment. Six months after completion of therapy the symptoms of HP-eradicated patients improved considerably (score values 17.4 +/- 1.5 and 10.2 +/- 0.8, respectively, p < 0.01) whereas symptoms of patients with persistent infection remained unchanged (21.1 +/- 1.7 and 20.4 +/- 1.5, n.s.) and only improved after successful retherapy (20.4 +/- 1.5 and 11.7 +/- 2.1, p < 0.05). In total, 17 of 20 patients (85%) improved after successful eradication. Also, neutrophil infiltration in the gastric mucosa correlated to both dyspeptic symptoms before therapy (r = 0.85) and the decrease in symptom score after HP-eradication (r = 0.61). In contrast, the symptoms of eight patients with gastroesophageal reflux disease were not improved after eradication (20.0 +/- 1.1 and 18.2 +/- 1.0, n.s.) CONCLUSIONS: HP-infection per se contributes to dyspepsia. 17 of 20 (85%) HP-positive dyspeptic patients improved after HP-eradication, when other potential organic causes for dyspepsia had been ruled out. However, many patients did not completely recover but the symptoms only partly decreased which parallels the persistence of part of the inflammatory infiltration in the gastric mucosa. This emphasizes the importance of HP-gastritis as an organic disease causing dyspeptic symptoms.

Microlaser-pumped periodically poled lithium niobate optical parametric generator-optical parametric amplifier.

For what is believed to be the first time, a single-longitudinal-mode passively Q-switched Nd:YAG microlaser is used to pump a narrow-bandwidth periodically poled lithium niobate (PPLN) optical parametric generator-optical parametric amplifier (OPG-OPA). Before amplification in the OPA, the output of the OPG stage was spectrally filtered with an air-spaced etalon, resulting in spectroscopically useful radiation (bandwidth, ~0.05 cm(-1) FWHM) that was tunable in 15-cm(-1) segments anywhere in the signal range 6820-6220 cm(-1) and the idler range 2580-3180 cm(-1). The ability to pump an OPG-OPA with compact, high-repetition-rate, intrinsically narrow-bandwidth microlasers is made possible by the high gain of PPLN. The result is a tunable light source that is well suited for use in portable spectroscopic gas sensors.

Rotational vibrational-rotational Raman differential absorption lidar for atmospheric ozone measurements: methodology and experiment.

A single-laser Raman differential absorption lidar (DIAL) for ozone measurements in clouds is proposed. An injection-locked XeCl excimer laser serves as the radiation source. The ozone molecule number density is calculated from the differential absorption of the anti-Stokes rotational Raman return signals from molecular nitrogen and oxygen as the on-resonance wavelength and the vibrational-rotational Raman backscattering from molecular nitrogen or oxygen as the off-resonance wavelength. Model calculations show that the main advantage of the new rotational vibrational-rotational (RVR) Raman DIAL over conventional Raman DIAL is a 70-85% reduction in the wavelength-dependent effects of cloud-particle scattering on the measured ozone concentration; furthermore the complexity of the apparatus is reduced substantially. We describe a RVR Raman DIAL setup that uses a narrow-band interference-filter polychromator as the lidar receiver. Single-laser ozone measurements in the troposphere and lower stratosphere are presented, and it is shown that on further improvement of the receiver performance, ozone measurements in clouds are attainable with the filter-polychromator approach.

[Ambulatory vs. inpatient intravenous antibiotic therapy in mucoviscidosis patients--a controlled study]. / Ambulante vs. stationäre intravenöse antibiotische Therapie bei Mukoviszidosepatienten--Eine kontrollierte Studie.

METHODS: 14 patients with cystic fibrosis and chronic pulmonary pseudomonas infection received four courses of two-week intravenous antibiotic therapy at home and during hospitalisation over an 18-month period. Following a controlled, intra-individual cross-over design, two courses of home therapy were followed by two courses of hospital treatment or vice versa. Parameters for inflammation, lung function, and body mass index were obtained at the beginning and end of each intravenous antibiotic therapy. Health-related quality of life, i.e. physical, emotional, social and functional components as well as happiness and medical care, was assessed at the end of each course. RESULTS: There was a trend towards better reduction of infection (p = 0.20 for leukocyte reduction) and improvement of lung function (p = 0.20 for FEV1 improvement) with hospital intravenous antibiotic therapy, although the differences did not attain statistical significance. Quality of life during therapy was significantly higher with home therapy regarding social (p < 0.01), functional and emotional subscales and happiness (all p < 0.05). The necessity for professional help and support from family and/or partner was emphasised. Individual answers showed that home therapy has the advantage of self-determination and continuity of daily life. Parents and partners felt impaired by day and night intravenous therapy at home. CONCLUSION: From our data we conclude that home intravenous antibiotic therapy is a useful option for a selected subgroup of patients with cystic fibrosis, but professional support and family aid is important to gain an effect similar to hospital treatment.

The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase.

Hematopoietic cell kinase (Hck) is a member of the Src-family of protein tyrosine kinases. We have found that upon enzymatic activation of Hck by the heavy metal mercuric chloride, there was a rapid increase in the levels of tyrosine phosphorylation of several proteins including the proto-oncogene p120(Cbl). Fibroblasts that are transformed with an activated allele of Hck exhibit constitutive Cbl phosphorylation. Upon Fcgamma receptor activation, a more physiologically relevant extracellular signal, Cbl is tyrosine phosphorylated and the Src-family selective inhibitor, PP1, can prevent this phosphorylation on Cbl. Hck phosphorylates Cbl in vitro and the interaction between Cbl and Hck is direct, requiring Hck's unique, SH3 and SH2 domains for optimal binding. Using a novel estrogen-regulated chimera of Hck we have shown a hormone-dependent association between Hck and Cbl in murine fibroblasts. This work suggests that Cbl serves as a key mediator of Hck induced signalling in hematopoietic cells.

Narrow-band, narrow-field-of-view Raman lidar with combined day and night capability for tropospheric water-vapor profile measurements.

We describe a high-performance Raman lidar system with combined day and night capability for tropospheric water-vapor profile measurements. The system incorporates high-performance UV interference filters and a narrow-band, dual-field-of-view receiver for rejection of background sunlight. Daytime performance has been demonstrated up to 5 km with 150-m vertical and 5-min temporal averaging. The nighttime performance is significantly better with measurements routinely extending from 10 to 12 km with 75-m range resolution and a 5-min temporal average. We describe design issues for daytime operation and a novel daytime calibration technique.

All-prism achromatic phase matching for tunable second-harmonic generation.

Achromatic phase matching (APM) involves dispersing the light entering a nonlinear optical crystal so that a wide range of wavelengths is simultaneously phase matched. We constructed an APM apparatus consisting of six prisms, the final dispersion angle of which was optimized to match to second order in wavelength the type I phase-matching angle of beta barium borate (BBO). With this apparatus, we doubled tunable fundamental light from 620 to 700 nm in wavelength using a 4-mm-long BBO crystal. An analogous set of six prisms after the BBO crystal, optimized to second order in second-harmonic wavelength, realigned the output second-harmonic beams. Computer simulations predict that adjustment of a single prism can compensate angular misalignment of any or all the prisms before the crystal, and similarly for the prisms after the crystal. We demonstrated such compensation with the experimental device. The simulations also indicate that the phase-matching wavelength band can be shifted and optimized for different crystal lengths.

Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin and 4-oxo-isotretinoin. A useful tool for management of severe acne.

BACKGROUND: Isotretinoin for oral therapy in severe acne conglobata and acne nodulocystica represents a significant achievement; however, the drug exerts several mucocutaneous and systemic adverse effects, besides its teratogenic potency. OBJECTIVE: The aim of this study was to investigate the plasma levels of isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne and to assess any correlation with the given dose, the clinical improvement and the occurrence of side effects. METHODS: Forty-one patients with severe acne and acne-related disorders were studied under long-term oral intake of isotretinoin. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxo-isotretinoin were measured by reversed-phase HPLC and were correlated with the administered oral dose and the number and frequency of side effects. RESULTS: Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75-1.0 mg/kg/day, 404 +/- 142 ng/ml were measured, whereas the plasma levels of 4-oxo-isotretinoin were 1-2x higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. CONCLUSION: The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.