Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment.

Background: Sarcoidosis is an immune-mediated systemic disease with unknown etiology affecting the lung predominantly. The clinical manifestation of sarcoidosis is rather diverse ranging from Löfgren's syndrome to fibrotic disease. Also, it differs among patients with distinct geographical and ethnic origins, consistent with environmental and genetic factors' role in its pathogenesis. Of those, the polymorphic genes of the HLA system have been previously implicated in sarcoidosis. Therefore, we have performed an association study in a well-defined cohort of Czech patients aiming to define how variation in HLA genes, may contribute to disease origin and development. Materials and methods: Total of the 301 Czech unrelated sarcoidosis patients were diagnosed according to international guidelines. In those, HLA typing was performed using next-generation sequencing. The allele frequencies at six HLA loci (HLA-A,-B,-C,-DRB1,-DQA1, and -DQB1) observed in the patients were compared with HLA allele distribution determined in 309 unrelated healthy Czech subjects; sub-analyses of relationships between HLA and distinct sarcoidosis clinical phenotypes were performed. Associations were assessed by two-tailed Fischer's exact test with correction for multiple comparisons. Results: We report two variants, HLA-DQB1*06:02, and HLA-DQB1*06:04, as risk factors for sarcoidosis, and three variants, HLA-DRB1*01:01, HLA-DQA1*03:01, and HLA-DQB1*03:02 as protective factors. HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, HLA-DQA1*05:01, and HLA-DQB1*02:01 variants associated with Löfgren's syndrome, a more benign phenotype. HLA- DRB1*03:01 and HLA-DQA1*05:01 alleles were connected with better prognosis-chest X-ray (CXR) stage 1, disease remission, and non-requirement of corticosteroid treatment. The alleles HLA-DRB1*11:01 and HLA-DQA1*05:05 are associated with more advanced disease represented by the CXR stages 2-4. HLA-DQB1*05:03 associated with sarcoidosis extrapulmonary manifestation. Conclusion: In our Czech cohort, we document some associations between sarcoidosis and HLA previously described in other populations. Further, we suggest novel susceptibility factors for sarcoidosis, such as HLA-DQB1*06:04, and characterize associations between HLA and sarcoidosis clinical phenotypes in Czech patients. Our study also extends the role of the 8.1 ancestral haplotype (HLA-A*01:01∼HLA-B*08:01∼HLA-C*07:01∼HLA-DRB1*03:01∼HLA-DQA1*05:01∼HLA-DQB1*02:01), already implicated in autoimmune diseases, as a possible predictor of better prognosis in sarcoidosis. The general translational application of our newly reported findings for personalized patient care should be validated by an independent study from another, international referral center.

Psychiatric patients' perception of physical restraint.

OBJECTIVE: To investigate psychiatric patients' subjective perception during and after belt fixation. METHOD: All patients who were involuntarily admitted and physically restrained at a psychiatric intensive care unit within an 18-month study period were analysed. Ratings were obtained at four visits when questioning was possible. RESULTS: Within a heterogeneous diagnostic sample of 47 patients, only 12 patients were eligible to participate during belt fixation. After cessation of fixation, eight patients lacked any memory of restraint, while 36 could be questioned. Visual analogue scale median scores indicated powerlessness and depressiveness rather than anxiety and aggression. Patients' acceptance of the coercive measure was significantly higher (P = 0.003), while patients' memory was significantly lower than expected (P < 0.001). About 50% of the patients documented high perceived coercion, and post-traumatic stress disorder (PTSD) could be supposed in a quarter of the restrained individuals. Subjective perceptions concerning fixation showed no significant changes over time. Results showed high interindividual variability. CONCLUSION: Visual analogue scale revealed that belt fixation seemed to be forgotten or accepted in the majority of patients, probably due to psychiatric intensive care, psychopharmacological treatment and clinical improvements. The responses of a quarter of the patients assessed before discharge may be in accordance with symptoms of PTSD.

Intensive care in psychiatry.

Psychiatric intensive care is supposed to offer treatment and to hold patients with psychiatric illness, if they pose a threat to themselves or to others. Besides treating the underlying psychiatric diagnoses, it is also necessary to take care of severe somatic comorbidity, which is often impeded by patients' limited ability to cooperate. Treatment often requires the administration of sedative medication and occasionally the use of medical restraints. Involuntary commitment, involuntary treatment and the usage of physical restraints is regulated by national mental health laws. Medical professionals working in the field of psychiatric intensive care must have expert knowledge in the fields of psychopharmacology and intensive care medicine. Treatment concepts should be aimed to provide optimized care for psychiatric inpatients in a potentially life-threatening phase of their illness. This article outlines current clinical practice at the psychiatric intensive care unit of the Medical University of Vienna (Austria). Furthermore, we present diagnoses, diagnostic procedures and specific treatments of a sample of 100 consecutive inpatients treated in the years 2008 and 2009 at this ward.

Reboxetine in the treatment of bulimia nervosa: a report of seven cases.

Controlled trials in patients with bulimia nervosa have demonstrated efficacy of antidepressant medications with serotonergic function (e.g. fluoxetine) as well as noradrenergic function (e.g. desipramine). Seven outpatients with bulimia nervosa according to DSM-IV criteria were treated openly with 8 mg of reboxetine, a selective noradrenaline reuptake inhibitor (NRI) over a 12-week period. The patients were assessed with the Structured Clinical Interview for DSM, Clinical Global Impression, 17-item Hamilton Depression Rating scale (HAM-D), Eating Disorder Inventory, Eating Disorders Questionnaire, daily self-ratings of eating behaviour, and the UKU side-effect rating scale. Three patients dropped out prematurely, one after 6 weeks and two after 4 weeks of reboxetine treatment. The reasons for premature attrition were rapid remission in one patient after 2 weeks and constipation, which led to an increase in episodes of laxative intake in two patients. In the total group, the monthly binge eating frequency showed a reduction of 73% and the frequency of vomiting episodes per month decreased by 67%. Furthermore, there was a concomitant decrease of depression ratings (HAM-D: from 12.2-6.1). Reboxetine seems to be an option for the treatment of bulimia nervosa.

[Diagnosis and therapy of eating disorders]. / Diagnose und Therapie von Essstörungen.

Even though there is no convincing evidence that eating disorders in general are on the rise, there has been an enormous increase in "treated" cases of patients with eating disorders. This review will cover important aspects of diagnosis and treatment of eating disorders. Psychotherapeutical and pharmacological treatment strategies in anorexia and bulimia nervosa will be discussed. For both eating disorders, psychotherapy is the treatment of choice. Drugs with a serotonergic function, e.g. serotonin-reuptake-inhibitors (SSRI), have demonstrated significant results in the treatment of bulimia nervosa and eating disorders with comorbid depression. In clinical practice "treatment packages" are offered because of the complexity of the disorders. The paper also deals with medical complications of eating disorders, motivational interviewing in anorexia nervosa and treatment with self-help manuals in bulimia nervosa.

[Osteoporosis in anorexia nervosa. New aspects of pathogenesis and therapy]. / Osteoporose bei Anorexia nervosa. Neue Aspekte der Pathogenese und Therapie.

Osteoporosis has been shown to be a relatively common complication of anorexia nervosa (AN). So far the exact mechanisms which are implicated are not fully clarified. Several factors such as malnutrition, reduced body weight, amenorrhea, and hypercortisolaemia seem to be involved. There is a strong relationship with the duration of amenorrhea and--in some studies--with the age of onset. Osteoporosis is for a long time a "silent" disease and the first symptoms such as back pain, loss of height, kyphosis, and fractures are late complications. Therefore, routine screening methods for bone density measurements should be established. The most accurate is the dual energy X-ray absorptiometry (DEXA). Therapeutically the primary aim should be to reach restoration of both normal body weight and regular menses. As AN is a chronic disease clinicians should be aware of the dangers of osteoporosis and start with the treatment and/or prevention of osteoporosis early. However, at this stage it is difficult to provide an evidence-based management plan for osteoporosis in AN. Hormone replacement therapy (HRT) as well as calcium and vitamin D-supplementation are under discussion, however, further controlled investigations are warranted.

Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.

Comorbidity of obsessive compulsive disorder in patients with eating disorders.

OBJECTIVE: We investigated the prevalence of obsessive compulsive disorder (OCD) among patients with eating disorders (ED). METHOD: 66 female inpatients who met the DSM-IV criteria for anorexia nervosa (AN) or bulimia nervosa (BN) participated in the study. The Structured Clinical Interview for DSM III-R diagnoses (SCID), the Eating Disorder Inventory (EDI), the revised 90-item Symptom-Checklist (SCL-90-R), the Beck Depression Inventory (BDI), and the Toronto Alexithymia Scale (TAS-20) were carried out. RESULTS: Twelve patients (18.2%) met the DSM-III-R criteria for lifetime OCD: 7 had a current OCD and 5 had a past history of OCD. These patients had significantly higher (more pathological) mean scores on the EDI and the SCL-90-R total scales. Analyses of the EDI subscales revealed significantly higher scores for ineffectiveness, perfectionism, interoceptive awareness, and maturity fears. As expected, analyses of the SCL-90-R subscales revealed significantly higher scores for OCD. In addition, there was a trend towards higher somatization scores in patients with comorbid OCD. We could not find any significant differences in the BDI and the TAS total scores. In addition, patients with comorbid OCD showed a significantly higher lifetime prevalence of bipolar disorder, simple phobia, and somatoform disorders. DISCUSSION: Our results confirm previous reports of a strong association between ED and OCD and suggest that the prevalence of OCD may be correlated with a higher severity of the eating disorder and general psychopathological parameters.

Endophotocoagulation in vitrectomy with a carbon dioxide laser.

A continuous-wave carbon dioxide laser operating at a wavelength of 10.6 microns has been applied transvitreally by means of a miniature articulating arm and intraocular probe to produce chorioretinal lesions in albino white rabbit eyes. The advantages of using a carbon dioxide laser are its lack of pigment dependence, its ability to act both as a photocoagulator and as a phototransector, and its ability to deposit its energy in a well-defined area without adverse effect on neighboring ocular tissue. The main disadvantage of the carbon dioxide laser in vitreoretinal surgery is that in a fluid medium, such as the vitreous, the laser tip must be placed in direct physical contact with the target tissue to obtain a reaction.

Syneresis of vitreous by carbon dioxide laser radiation.

In carbon dioxide laser surgery of the vitreous a process of vaporization has been advocated. In this report syneresis, a thermal liquefaction of gel, is shown to be over ten times more efficient on an energy basis than vaporization. Syneresis of vitreous is experimentally shown to be a first-order kinetic process with an activation energy of 41 +/- 0.5 kilocalories per mole. A theory of laser surgery in which this figure is used agrees closely with results from laser experiments on human eye-bank vitreous. The syneresis of vitreous by carbon dioxide laser radiation could lead to a more delicate form of ocular microsurgery, and application to other biological systems may be possible.