[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.

Ocular delivery systems for poorly soluble drugs: an in-vivo evaluation.

For highly potent but poorly water-soluble drugs like cyclosporine A, the development of aqueous formulations providing an increase of corneal drug tissue levels, and thus of bioavailability, to increase patient compliance is still a challenge. Therefore, we designed two water-based liquid application systems, an in-situ nanosuspension (INS) and a micellar solution (MS), and tested both formulations in vivo at the rabbit cornea for tolerability and the tissue uptake of CsA. The evaluation of the biological tolerability by periodical eye examination during 180 min and quantification in a defined grading system revealed that the INS evoked minimal to no irritations whereas the MS was perfectly tolerated. After the observation period, the rabbits were sacrificed and the corneal tissue levels of CsA were analyzed. The INS and the MS both showed high levels of 1683±430 ngCsA/gcornea and 826±163 ngCsA/gcornea, respectively, and exceeded drug tissue levels reported for Restasis(®) (350 ngCsA/gcornea) and cationic emulsions (750 ngCsA/gcornea). These results marked our INS and MS as outstanding novel approaches for the treatment of inflammatory corneal diseases.

[Black spots in the eye]. / Schwarzer Fleck am Auge.

Senile scleral plaques are characterized by a calcification located at the insertion of the horizontal rectus muscles. As a possible cause for their development a combination of solar tissue damage and continuous mechanical stress is discussed. We present a case of a 76-year-old male whose wife noticed expulsion of a calcified scleral plaque while applying antiglaucoma eyedrops. The local antiglaucoma therapy was stopped and acetacolamide was administered. Local therapy consisted of hyaluronic acid eyedrop and calcium pantothenate and retinol palmiate eye ointment. This treatment led to a rapid reepithelialization. The expulsion of calcified senile scleral plaques is a described complication which can necessitate surgical treatment.

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.

[Cataract surgery. Effect on the posterior segment of the eye]. / Kataraktoperation. Effekt auf den hinteren Augenabschnitt.

Cataract surgery is a safe procedure with a high patient satisfaction rate. However, pseudophakia changes the physiology of the eye and immediate changes include release of inflammatory cytokines. Deformation of the globe and intraoperative fluctuations of intraocular pressure may induce microlesions and alterations of ocular perfusion. The barrier function between the anterior and the posterior segment is compromised after surgery and the geometry of the intraocular chambers changes. Especially the vitreous body is subject to increased destruction during the years after surgery. The occurrence of pseudophakic cystoid macular edema after cataract surgery is a well known complication. Several studies have described a progression of diabetic retinopathy, especially of diabetic macular edema after cataract surgery. In contrast cataract surgery does not seem to have a significant impact on the progression of age-related macular degeneration. However the risk for retinal detachment is significantly increased in pseudophakia for at least 10 years after surgery. Awareness of special risk factors can make cataract surgery, one of the most effective procedures in medicine, even safer.

Deficiencies of folate and vitamin B12 do not affect fracture healing in mice.

PURPOSE: Recently, hyperhomocysteinemia has been shown to be associated with impaired fracture healing in mice. The main causes for hyperhomocysteinemia are deficiencies of folate and vitamin B12. However, there is no information on whether deficiencies of these B vitamins are affecting bone repair, too. METHODS: We used two groups of mice to investigate the impact of folate and vitamin B12 deficiency on fracture healing: mice of the first group were fed a folate- and vitamin B12-deficient diet (n=14), while mice of the second group received an equicaloric control diet (n=13). Four weeks after stabilizing a closed femur fracture, bone repair was analyzed by histomorphometry and biomechanical testing. In addition, serum concentrations of homocysteine, folate, vitamin B12, the bone formation marker osteocalcin (OC), and the bone resorption marker collagen I C-terminal crosslaps (CTX) were measured. RESULTS: Serum analyses revealed significantly decreased concentrations of folate and vitamin B12 in animals fed the folate- and vitamin B12-deficient diet when compared to controls. This was associated with a moderate hyperhomocysteinemia in folate- and vitamin B12-deficient mice, while no hyperhomocysteinemia was found in controls. Three-point bending tests showed no significant differences in callus stiffness between bones of folate- and vitamin B12-deficient animals and those of control animals. In accordance, the histomorphometric analysis demonstrated a comparable size and tissue composition of the callus, and also serum markers of bone turnover did not differ significantly between the two groups. CONCLUSIONS: We conclude that folate and vitamin B12 deficiency does not affect bone repair in mice.

[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.

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.

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.

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.

[Review of the role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric disorders--current evidence and preliminary recommendations]. / Hyperhomocysteinämie und B-Vitaminmangel bei neurologischen und psychiatrischen Erkrankungen--Aktueller Kenntnisstand und vorläufige Empfehlungen.

Elevated concentration of total homocysteine (Hcy) in plasma (> 12 micromol/l) is a risk factor for several diseases of the central nervous system. Epidemiological studies have shown a dose-dependent relationship between concentrations of Hcy and the risk for neurodegenerative diseases. Hcy is a marker for B-vitamin deficiency (folate, B12, B6). Hyperhomocysteinemia (HHcy) causes hypomethylation which is an important mechanism that links Hcy to dementia. Supplementation with vitamins B aims at reducing the risk of neurodegenerative diseases. Current evidence suggests that Hcy-lowering treatment has a positive effect for the secondary and primary prevention of stroke. HHcy is very common in patients with Parkinson disease particularly those who receive L-dopa treatment. Furthermore, a positive association has been reported between HHcy and multiple sclerosis. Moreover, HHcy and vitamin B deficiency are reported to have a causal role in depression, and epilepsy. In addition several anti-epileptic drugs cause secondary HHcy. Therefore, sufficient intakes of the vitamins are recommended for patients who have already developed neuropsychiatric diseases. Vitamin B deficiency should be suspected in children with development disorders, failure to thrive and unexplained neurological manifestations. Elderly people are also an important at-risk group where vitamin B deficiency and HHcy have been linked to neurodegenerative diseases. Treatment with folate, B12, and B6 can improve cerebral function. Preventive vitamin B supplementation and sufficient intake seem very important for secondary and primary prevention of neuropsychiatric disorders, especially in subjects with a low intake or status of the vitamins.

Electrophysiological subtypes of psychotic states.

OBJECTIVE: This research sought neurobiological features common to psychotic states displayed by patients with different clinical diagnoses. METHOD: Cluster analysis with quantitative electroencephalographic (QEEG) variables was used to subtype drug-naïve, non-medicated, and medicated schizophrenic, depressed and alcoholic patients with psychotic symptoms, from the USA and Germany. QEEG source localization brain images were computed for each cluster. RESULTS: Psychotic patients with schizophrenia, depression and alcoholism, and drug- naïve schizophrenic patients, were distributed among six clusters. QEEG images revealed one set of brain regions differentially upregulated in each cluster and another group of structures downregulated in the same way in every cluster. CONCLUSION: Subtypes previously found among 94 schizophrenic patients were replicated in a sample of 390 non-schizophrenic as well as schizophrenic psychotics, and displayed common neurobiological abnormalities. Collaborative longitudinal studies using these economical methods might improve differential understanding and treatment of patients based upon these features rather than clinical symptoms.

Interaction of drug molecules with carrier systems as studied by parelectric spectroscopy and electron spin resonance.

According to recent investigations of nanoparticular carrier systems the mode of drug-particle interaction appears to influence drug penetration into the skin. For a more detailed insight into the molecular structure of drug loaded particles the two independent analytical methods, namely the parelectric spectroscopy (PS) and the electron spin resonance (ESR) have been applied to 4,5,5,-trimethyl-1-yloxy-3-imidazoline-2-spiro-3'-(5'()-cholestane) as a model drug. Spectra have been analyzed in dependence on the concentration of the spin label. Changes in the concentration-dependent dipole mobility and dipole density given by PS and the concentration-dependent rotational correlation time (ESR) which are a measure of the vicinity of carrier and/or the surfactant and guest molecule were studied with cholestane-labeled solid lipid nanoparticles (SLN), nanoparticular lipid carriers (NLC) and nanoemulsions (NE). The spin probes were attached to the SLN surface which consists of two distinct sub-compartments: the rim and the flat surface of the disk-like shapes. The shape could be observed by freeze-fraction electron microscopy. Spin probes, however, were incorporated into the carrier matrix in the cases of NLC and NE. Results of PS are verified by ESR which allows a more detailed insight. Taking the results together a detailed new model of 'drug'-particle interaction could be established.