[Ambulatory care of patients with somatically unexplained complaints : A comparative qualitative study]. / Die ambulante Betreuung von Patienten mit somatisch nicht erklärten Beschwerden : Eine vergleichende qualitative Studie.

BACKGROUND: The aim of this study was to compare the approach of general practitioners (GP) and outpatient specialists for psychiatry, neurology or psychosomatic medicine to patients with somatically unexplained complaints. METHODS: Qualitative interviews were conducted with general practitioners in Berlin and with outpatient specialists. Interviews were analyzed by qualitative content analysis. RESULTS: Both GPs and specialists rarely used structured diagnostic instruments. Guidelines are seen and used with reservation throughout the different specialties. Similar to the GPs, most of the specialists surveyed in this study had reservations against the necessity of a precise coding according to the International Classification of Diseases (ICD). CONCLUSION: In outpatient care the concern for the individual patient is the connecting element between different medical specialties. This results in a differential diagnostic and therapeutic approach that is not automatically in line with guidelines. The development of common concepts in ambulatory care might help to meet the demands of this complex group of patients with somatically unexplained complaints.

[Contract Conditions for GPs in Training while Working in Ambulatory Care]. / Vertragsbedingungen von ambulant tätigen Ärzten in Weiterbildung zum Facharzt für Allgemeinmedizin.

BACKGROUND: In Germany, the situation of GPs in training has received growing attention. Central funding of GPs in training who are working in ambulatory care has been increased up to 3 500 Euros/month. However, the contract conditions of GPs in training who are working in ambulatory care have been unknown as yet. METHODS: An online survey was undertaken. We recruited GPs in training by snowball sampling making use of national and local organisations of GPs and GPs in training. Our questionnaire consisted of questions concerning sociodemographic variables, gross wage, working hours, holidays and free days for educational purposes. Data were analysed by descriptive statistical methods. RESULTS: 152 participants fulfilled the inclusion criteria. 127 were full time GPs in training. The median of gross wage was 3 500 Euros/month, the mean gross wage was 3 878 Euros/month. The gross wage per hour was lower than that for GPs in training who are working in hospitals. Especially part time GPs in training had a lower gross wage per hour. One third of the GPs in training had no free days for educational purposes. More than half of the GPs in training had a weekly meeting with their supervisor, however, more than one third of GPs in training had no or only irregular meetings with their supervisor. CONCLUSIONS: In Germany, GPs in training earn in ambulatory care less than in hospital care. They do not have sufficient free days for educational purposes and often there is a lack of supervision. This seems to indicate that GPs in training are mainly considered as cheap coworkers instead of trainees.

[Psychological factors and sleep in the lifeworld nursing home from the nursing home residents' perspective. A qualitative study]. / Psychische Faktoren und Schlaf in der Lebenswelt Pflegeheim aus der Sicht von Pflegeheimbewohnern. Eine qualitative Studie.

BACKGROUND: Sleep disorders are common among nursing home residents. However, the possible involvement of psychological factors has been given little attention up until now. We investigated nursing home residents' perspective on psychological factors and sleep disorders within the nursing home environment. MATERIALS AND METHODS: We conducted a qualitative interview study comprising episodic interviews with 30 nursing home residents in five different nursing homes. The data was analysed by thematic coding. RESULTS: Nursing home residents require peace of mind in order to sleep well. Ruminations and thoughts disturb inner peace and are, in turn, caused by psychological factors. Of particular relevance is the end-of-life situation of the residents. Nursing home residents possess only limited strategies to relax and achieve inner peace. CONCLUSION: Psychosocial factors play a central role in sleep disturbances among nursing home residents. Nurses and physicians who treat nursing home residents with sleep disorders should consider the possible psychosocial causes. Counselling and treatment should be given on an individual basis, for example by educating in relaxation techniques.

Distribution profiles of nitroxide spin probes in human skin--a combined study using spatially resolved electron spin resonance spectroscopy and mass spectrometry.

Electron spin resonance spectroscopy and mass spectrometry are two analytical methods that are very rarely used in combination. In this paper, we will show that the methods complement one another in the example of the distribution of stable nitroxide radicals in human skin, including the spatial resolution of these distribution processes. There are many ESR investigations dealing with this subject, but unfortunately, they are all limited to the detection of paramagnetic species. The combination with MS allows the successful examination of the distribution profile of the main biotransformation product of the nitroxide radicals, the respective "ESR-silent" hydroxylamines. In order to maintain the biological state of the sample material as far as possible, atmospheric pressure matrix-assisted laser desorption/ionization with ion trap detection has been used for the mass spectrometric investigations. The results validate the former findings of the strong reduction of stable free radicals by biological material; moreover, the diamagnetic species formed during these processes have been identified.

[Pseudophakic retinal detachment]. / Pseudophakie-Ablatio.

Modern phacoemulsification has established itself as a safe and very rewarding surgical procedure. Patients and surgeons may not associate late complications with the initial surgery. However, recent studies have demonstrated that such a causal relationship may persist for many years after the cataract procedure and that there is a significant increase in the risk for developing a retinal detachment during the postoperative years. The mean time period between cataract surgery and pseudophakic retinal detachment is between 3 and 4 years. Even uncomplicated cataract surgery alters the physiological processes within the eye and can lead to progressive destruction of the vitreous for many years after the surgery. Therefore, the risk for a retinal detachment is increased for at least 10 years after the initial procedure. In recent epidemiological studies, the most important risk factors for pseudophakic retinal detachment were myopia, younger age and male gender. If all factors are combined, the cumulative risk for developing a retinal detachment after cataract surgery may rise to 20 %. Additional factors that may increase this risk are additional intraoperative complications, for example, rupture of the posterior capsule, vitreous loss or dropped nucleus. Compared to phakic retinal detachments, pseudophakic patients on average present with a shorter history of visual symptoms, are older, more commonly male and display fewer, smaller and more anteriorly located retinal breaks that frequently are only detected during surgery. The anatomic success rates have improved significantly over the past years, in particular through the advances and increasing popularity of primary vitrectomy. However, functional results are still disappointing. Only about half of the patients will achieve reading ability without low vision aids. The increased and long-term risk for pseudophakic retinal detachment should be part of the preoperative consent process of any cataract surgery, in particular, in young myopic males.

[Ophthalmological findings as a hint for systemic disease]. / Ophthalmologische Befunde als Hinweis auf internistische Erkrankungen.

Many eye diseases are associated with systemic diseases. Moreover, ophthalmological findings can be first manifestations of systemic diseases. Therefore internists and ophthalmologists should be familiar with the signs, symptoms, and the management of eye diseases with a possible systemic association. Due to subspecialization in medicine an interdisciplinary approach is mandatory for optimal patient care. In this article examples of eye diseases with a possible association with systemic diseases are presented.

Hyperhomocysteinemia is associated with impaired fracture healing in mice.

Hyperhomocysteinemia (HHCY) has been shown to disturb bone metabolism and to increase the incidence of osteoporosis and osteoporotic fractures. However, there is a complete lack of information on whether these metabolic alterations affect bone repair. The aim of this study was to analyze the impact of HHCY on fracture healing. One group of mice was fed a homocystine-supplemented diet (n = 12), whereas another group received the accordant standard diet for control (n = 13). Four weeks after the stable fixation of a closed femoral fracture, animals were killed to prepare bones for histomorphometric and biomechanical analyses. In addition, blood samples were obtained to evaluate serum concentration of homocysteine (HCY). Quantitative analysis of blood samples revealed severe HHCY as indicated by significantly increased serum concentrations of HCY in animals fed the homocystine-supplemented diet (102.2 +/- 64.5 micromol/l) compared to controls (2.8 +/- 1.5 micromol/l). Biomechanical evaluation of bone repair revealed significantly decreased bending stiffness of the femora of homocystine-fed animals (45.5 +/- 18.2 N/mm) compared with controls (64.6 +/- 15.8 N/mm). Histomorphometric analysis demonstrated a slightly smaller callus diameter in HHCY animals but no significant differences in the tissue composition of the callus. In conclusion, the homocystine-supplemented diet leads to severe HHCY, which is associated with an impaired biomechanical quality of the healing bone.

Cartilage ultrastructure after high pressure freezing, freeze substitution, and low temperature embedding. I. Chondrocyte ultrastructure--implications for the theories of mineralization and vascular invasion.

Electron microscopic examination of epiphyseal cartilage tissue processed by high pressure freezing, freeze substitution, and low temperature embedding revealed a substantial improvement in the preservation quality of intracellular organelles by comparison with the results obtained under conventional chemical fixation conditions. Furthermore, all cells throughout the epiphyseal plate, including the terminal chondrocyte adjacent to the region of vascular invasion, were found to be structurally integral. A zone of degenerating cells consistently observed in cartilage tissue processed under conventional chemical fixation conditions was not apparent. Hence, it would appear that cell destruction in this region occurs during chemical processing and is not a feature of cartilage tissue in the native state. Since these cells are situated in a region where tissue calcification is taking place, the implication is that the onset and progression of cartilage calcification are, at least partially, controlled by the chondrocytes themselves. The observation that the terminal cell adjacent to the zone of vascular invasion is viable has important implications in relation to the theory of vascular invasion. This may now require reconceptualization to accommodate the possibility that active cell destruction may be a precondition for vascular invasion.

Efficacy and safety of lornoxicam compared with placebo and diclofenac in acute sciatica/lumbo-sciatica: an analysis from a randomised, double-blind, multicentre, parallel-group study.

AIM: The efficacy and safety of oral lornoxicam (LNX) as early treatment of acute sciatica/lumbo-sciatica was compared with placebo and diclofenac in a 5-day double-blind, randomised study. METHODS: Male or female patients (n = 171) aged 18-70 years with acute sciatica or lumbo-sciatica [acute sciatica defined as typical radiation of pain along the sciatic nerve (including radiating pain below the knee) and worsening of pain as defined by Lasegue's leg-raising test (< 60 degrees ) within 72 h and previous attack ceased > 3 months previously; lumbo-sciatica defined as symptoms of sciatica with concurrent lumbar pain and a predefined minimum pain score]. The dosage of study treatment was 8-24 mg/day LNX, 100-150 mg/day diclofenac or placebo. The primary end-point was the difference in pain intensity difference from baseline to 6 h (PID(0-6 h)) after the first dose of study treatment. Secondary end-points were pain relief, the cumulative sums of pain intensity difference and total pain relief on day 1 and on days 2-4. RESULTS: In total, 164 patients completed the study. Significant differences in PID between LNX and placebo were seen in the time interval 3-8 h after the first dose including PID(0-6 h) (p = 0.015). Secondary end-points favoured LNX vs. placebo, but in general were not significantly different. LNX and diclofenac had similar analgesic effect. Incidence and severity of adverse events were comparable for the three treatments; overall tolerability was rated as very good/good by 93% of the patients. CONCLUSION: These data indicate that the analgesic efficacy of LNX is superior to placebo and similar to diclofenac in acute sciatica/lumbo-sciatica.

[Surgical treatment of diabetic macular oedema]. / Chirurgische Therapie des diabetischen Makulaödems.

The therapy for diabetic macular oedema often remains unsatisfactory for both patient and treating physician. Therapeutic approaches comprise laser therapy as the evidence-based "basic therapy" and increasingly also intravitreal injections of drugs which, however, have only a limited effect. One argument for the use of vitrectomy in the treatment of diabetic macular oedema is its potentially permanent positive effect. On the one hand, removal of the adherent vitreous may facilitate the supply of the inner retina "per diffusionem" from the vitreous, on the other hand it may allow movement of harmful cytokines from the retina into the vitreous also by diffusion. Furthermore, from the pathophysiological standpoint, the vitreoretinal interface itself is modified by glycosylation processes and may thereby contribute to the occurrence of macular oedema. Pathological vitreofoveolar adhesions, which now can be visualised by use of ocular coherence tomography, may also add to the development of macular oedema in a mechanical-tractive manner. A critical analysis of the published clinical studies reveals that the macular retinal thickness is indeed reduced after vitrectomy, disappointingly however, this does not translate into better visual acuity in patients without detectable tractive components. But, in the case of eyes with tractive components of the diabetic macular oedema, there is good evidence for a surgical approach.

Plasma homocysteine levels & 677C-->T methylenetetrahydrofolate reductase gene polymorphism in patients with coronary artery disease of different severity.

BACKGROUND & OBJECTIVE: Numerous studies have identified hyperhomocysteinemia as an independent risk factor for coronary artery disease (CAD). Furthermore, influences of polymorphysim of methylenetetrahydrofolate reductase (MTHFR) on homocysteine levels are documented. However, the relationship between severity of CAD and polymorphism of MTHFR has not been systematically evaluated. The present study was undertaken to evaluate this relationship in patients undergoing coronary artery bypass surgery. METHODS: Serum homocysteine and MTHFR polymorphism in relation to severity of CAD was examined in 113 male patients, who all underwent coronary artery bypass surgery. The prevalences of 677 C-->T transition of the MTHFR gene were determined in these patients. Two groups were compared according to GENSINI coronary score : mild atherosclerosis (CAD stenosis < 30) and severe atherosclerosis (CAD stenosis > 30). RESULTS: Patients with CAD showed a significantly higher serum concentration of homocysteine than control subjects (P < 0.01). The serum homocysteine level was significantly higher in patients with increased scores than in patients with mild CAD (Gensini score < 30) both with and without the MTHFR polymorphism. INTERPRETATION & CONCLUSION: The findings of our study showed that hyperhomocysteinemia was significantly related to the severity of CAD independent on MTHFR polymorphism.

Exercise-induced increases in NT-proBNP are not related to the exercise-induced immune response.

OBJECTIVE: To investigate if the exercise-induced immune response contributes to the exercise-induced increase in brain natriuretic peptide (BNP) in healthy athletes. This has previously been speculated, as elevated concentrations of BNP or N-terminal pro brain natriuretic peptide (NT-proBNP) in cardiovascular patients were found to be related to immune reactions and elevations in inflammatory cytokines such as interleukin 6 (IL-6). METHODS: Stored serum samples were analysed for NT-proBNP concentrations of 14 healthy endurance athletes (mean age: 25 (SD 5) years; VO(2peak) 67 (SD 6) ml/min/kg), who had been examined previously for exercise-induced immune reactions and their dependence on carbohydrate supplementation (6 or 12% carbohydrate vs placebo beverages) after three bouts of 4 h cycling at a given workload of 70% of the individual anaerobic threshold. Venous blood samples were taken before, immediately after, and 1 h and 1 day after exercise. Leucocyte subpopulations were determined immediately after blood sampling by flow cytometry. Serum samples for posterior analysis of C-reactive protein (CRP), IL-6, cortisol and NT-proBNP were stored at -80 degrees C. RESULTS: The exercise-induced increases in NT-proBNP (p<0.001) were not related to the exercise-induced immune response, although exercise induced marked (CHOS-dependent) increases in IL-6, CRP, cortisol, leucocytes, neutrophils, monocytes and natural killer cells. CONCLUSION: It is unlikely that the exercise-induced increases in NT-proBNP or BNP in healthy athletes are caused by the exercise-induced immune response. Therefore, exercise-induced increases in NT-proBNP or BNP in healthy athletes have to be differentiated from increases in cardiovascular patients with systemic inflammation.

Fuzzy classification by fuzzy labeled neural gas.

We extend the neural gas for supervised fuzzy classification. In this way we are able to learn crisp as well as fuzzy clustering, given labeled data. Based on the neural gas cost function, we propose three different ways to incorporate the additional class information into the learning algorithm. We demonstrate the effect on the location of the prototypes and the classification accuracy. Further, we show that relevance learning can be easily included.

Prevalences of hyperhomocysteinemia, unfavorable cholesterol profile and hypertension in European populations.

BACKGROUND: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD. OBJECTIVES: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD. DESIGN: Cross-sectional data on 12,541 men and 12,948 women aged 20 + y were used from nine European studies. RESULTS: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60+ years). CONCLUSIONS: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid.

Eight novel LDL receptor gene mutations among patients under LDL apheresis in Dresden and Leipzig.

LDL apheresis is highly efficient in reducing elevated plasma cholesterol. Due to strict indications only patients with severe, refractory hypercholesterolemia are treated with this method. Mutations in the LDL receptor gene are major genetic causes for severe hypercholesterolemia. Screening the entire gene in LDL apheresis patients from Saxony should determine whether an increased frequency of defined mutations is responsible for the atherogenic hypercholesterolemia in this group. 31 unrelated patients (15 male, 16 female, age 33-71 yrs.) were included in the analysis. The LDL-R gene was screened using SSCP and/or automated sequencing. The familial defective apolipoprotein B-100 (FDB) mutation was genotyped using established PCR techniques. Nineteen of 31 patients were carriers of an LDL-R mutation. Ten missense and two nonsense mutations, three insertions and two deletions were detected. The mutations C74S, C74R, T87M, 660delC, 662insCCCCG, 680insGGACAAATCTGA, 1428insC and 2167delG have not been previously described. One patient was compound heterozygous for two missense mutations. Two further patients were heterozygous for FDB. No mutations were found among controls. A genetic background for hypercholesterolemia in the LDL-R could be established in about 61% of the patients examined. Therefore, methods of DNA analysis allow to recognize and adequately treat a large portion of high-risk individuals at an early stage.

Inhibition of denuded mouse oocyte meiotic maturation by forskolin, an activator of adenylate cyclase.

Forskolin, a diterpene that activates rapidly adenylate cyclase activity in several somatic cell systems, prevents spontaneous meiotic maturation of denuded mouse oocytes (ED50 of inhibition approximately 2.5 microM), unlike cholera toxin. The oocyte is sensitive to the action of forskolin during the period preceding germinal vesicle breakdown (GVBD). Washing of the cells abolishes the effect. The diterpene potentiates the inhibitory effect of iso-butyl-methyl-xanthine (IBMX), a phosphodiesterase inhibitor, and it increases cAMP concentration in the oocytes. These findings not only confirm the antagonistic effect of cAMP on the first step of meiosis reinitiation (GVBD) in mammalian oocytes, but also provide the first demonstration of a functional adenylate cyclase system in mammalian oocytes upon which regulatory signals may act.

Human seminal plasma contains a protein that shares physicochemical, immunochemical, and immunosuppressive properties with pregnancy-associated plasma protein-A.

Pregnancy-associated plasma protein-A (PAPP-A) was detected by RIA in human seminal plasma. This was not due to interference with proteases or binding to seminal plasma proteins, since immunoreactivity was not affected by treatment with protease inhibitors, and the elution of [125I]PAPP-A was not altered by preincubation with seminal plasma. The major component of the seminal plasma PAPP-A coeluted with pure PAPP-A or plasma PAPP-A from pregnant and nonpregnant women. In the RIA, serial dilutions of seminal plasma gave parallel displacement curves to pregnancy plasma. Removing PAPP-A-like material from seminal plasma by adsorbtion to heparin-Sepharose reduced the inhibitory effect of seminal plasma on phytohemagglutinin-induced lymphocyte transformation. The source of seminal plasma PAPP-A-like immunoreactive material remains to be elucidated, but it is unlikely to be the testis, since PAPP-A levels in semen of vasectomized men were similar to those in nonvasectomized men.

Time-of-day variations of indicators of attention: performance, physiologic parameters, and self-assessment of sleepiness.

BACKGROUND: A study was performed to analyze time-of-day variations of different indicators of attention and their interrelations. METHODS: After a sufficiently long all-night sleep 12 healthy non-sleep-deprived subjects ran through a test battery (Stanford Sleepiness Scale, Visual Analogue Scale, Critical Flicker Fusion Test [CFF], Visualization Test, Number Facility Test, Reaction Time, Pupillometry, and modified Multiple Sleep Latency Test) every 2 hours from 7:00 AM until 11:00 PM. Time-of-day variations were tested nonparametrically with Friedman's test for repeated measurements. Principal component factor analysis (of individually standardized values) was used to identify variable complexes with the same pattern of time-of-day variation. RESULTS: Statistically significant time-of-day variations were found for all variables, except for Fusion Frequency in CFF and Reaction Time. In factor analysis the physiologic parameters (pupillometric variables and sleep latencies) load on one factor, whereas the self-assessment scales, the Visualization Test, Number Faculty Test, and CFF load on the second factor. The variables that load primarily on factor 1 show peak levels of alertness immediately after getting up (at 7:00 AM) and again at 9:00 PM. Those variables that load primarily on factor 2 indicate a peak level of alertness around noon (11:00 AM-3:00 PM). CONCLUSIONS: Different aspects of attention follow different time-of-day variations. It is discussed, that these findings can be attributed to underlying circadian and homeostatic factors.