First ex vivo cultivation of human Demodex mites and evaluation of different drugs on mite proliferation.

BACKGROUND: Demodex spp. mites are the most complex resident of the human skin microbiome. Although they are considered commensals, they can be pathophysiologically relevant in inflammatory skin diseases like rosacea. Until now, there is no culture system available for these mites except for using live vertebrate hosts. OBJECTIVES: Our aim was to establish an ex vivo culture of human Demodex mites and to characterize the sebogenesis-dependent mite density. METHODS: Demodex mites were cultivated in pilosebaceous units of human skin explants, called human organotypic skin explant culture (hOSEC). Furthermore, different sebogenesis-modifying additives were evaluated. Mites and mite survival were evaluated using light and fluorescence microscopy. RESULTS: After 90 days of incubation, living Demodex mites - including eggs, larvae and nymphs - were detected in the dissected skin samples. Incubation for 30 days with anabolic steroids (testosterone and trenbolone) as well as retinol and retinoic acid (isotretinoin) yielded a reduced mite density. CONCLUSIONS: With this technique, mites can be cultivated ex vivo for the first time, thereby establishing new ways to investigate Demodex spp. The sebostatic effect of isotretinoin might explain the mechanism of action in the off-label treatment of rosacea. We anticipate our findings to be the basis of an accelerated research on our most complex commensal, its life, biology and physiology.

Effects of controlled ovarian stimulation on vascular barrier and endothelial glycocalyx: a pilot study.

PURPOSE: Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS. METHODS: Serum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17). RESULTS: Patients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml 6.1125th-19.1375th to 13.9 ng/ml 9.625th-28.975th; p=0.026), indicating shedding and degradation of the EGX. CONCLUSION: A shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.

Fluid resuscitation after severe trauma injury : U-shaped associations between tetrastarch dose and survival time or frequency of acute kidney failure.

BACKGROUND: Using tetrastarch for fluid resuscitation after a severe trauma injury may increase risks of death and acute kidney injury. The importance of tetrastarch dose, however, is unknown. METHODS: A retrospective observational study was performed in two trauma centres using data on type and amount of fluids (balanced crystalloids or tetrastarch) used for pre- and acute in-hospital shock management. We evaluate independent associations between the relative and absolute volumes of tetrastarch and 90-day survival time or the frequency of severe acute kidney failure (AKF). RESULTS: We studied 271 patients who had sustained a severe blunt trauma injury (average predicted mortality according to the Revised Injury Severity Classification Score (RISC) 15.1 ± 1.4% [mean, standard deviation]), and who had required more than 2 days of intensive care therapy. In all, 75.3% of patients had received tetrastarch with a crystalloid/colloid ratio of 2.93 ± 2.60. The 90-day mortality was 11.1%, and 7.8% of the patients developed severe AKF. After adjusting for confounders, we found a U-shaped, nonlinear association between absolute or relative volumes of tetrastarch and survival time (p = 0.003 and 0.025, respectively). Optimal relative volumes of tetrastarch approximately ranged from 20 to 30% of total fluids. Giving less than about 1000 ml, or more than about 2000 ml tetrastarch was significantly associated with an increased risk of developing severe AKF (p = 0.023). CONCLUSIONS: There was a complex U­shaped association between the tetrastarch dose and morbidity/mortality of patients after a severe trauma injury. The optimal crystalloid/tetrastarch ratio for acute shock management appears to range from about 2.5 to 4.0.

State of the art in fluid and volume therapy : A user-friendly staged concept. English version.

Adequate intraoperative infusion therapy is essential for the perioperative outcome of a patient. Both hypo- and hypervolemia can lead to an increased rate of perioperative complications and to a worse outcome. Perioperative infusion therapy should therefore be needs-based. The primary objective is the maintenance of preoperative normovolemia using a rational infusion strategy. Perioperative fluid losses should be differentiated from volume losses due to surgical bleeding or protein losses into the interstitial space. Fluid loss via urine excretion or insensible perspiration (0.5-1.0 ml/kg/h) should be replaced with balanced, isooncotic, crystalloid infusion solutions in a ratio of 1:1. Volume therapy stage 1: intraoperative volume losses up to a blood loss corresponding to 20% of the patient's total blood volume are compensated for by balanced crystalloids in a ratio of 4-5:1. Stage 2: blood losses exceeding this level are to be treated with isooncotic colloids (preferably balanced) in a 1:1 ratio. In this regard taking into consideration the contraindications, e. g., sepsis, burns, critical illness (usually patients in the intensive care unit), impaired renal function or renal replacement therapy, intracranial hemorrhage, or severe coagulopathy, artificial colloids such as hydroxyethyl starch (HES) can be used perioperatively for volume replacement. Stage 3: if an allogeneic blood transfusion is indicated, blood and blood products are applied in a differentiated manner.

[State of the art in fluid and volume therapy : A user-friendly staged concept]. / Stand der Wissenschaft in der Flüssigkeits- und Volumentherapie : Ein anwenderfreundliches Stufenkonzept.

Adequate fluid therapy is highly important for the perioperative outcome of our patients. Both, hypovolemia and hypervolemia can lead to an increase in perioperative complications and can impair the outcome. Therefore, perioperative infusion therapy should be target-oriented. The main target is to maintain the patient's preoperative normovolemia by using a sophisticated, rational infusion strategy.Perioperative fluid losses should be discriminated from volume losses (surgical blood loss or interstitial volume losses containing protein). Fluid losses as urine or perspiratio insensibilis (0.5-1.0 ml/kg/h) should be replaced by balanced crystalloids in a ratio of 1:1. Volume therapy step 1: Blood loss up to a maximum value of 20% of the patient's blood volume should be replaced by balanced crystalloids in a ratio of 4(-5):1. Volume therapy step 2: Higher blood losses should be treated by using iso-oncotic, preferential balanced colloids in a ratio of 1:1. For this purpose hydroxyethyl starch can also be used perioperatively if there is no respective contraindication, such as sepsis, burn injuries, critically ill patients, renal impairment or renal replacement therapy, and severe coagulopathy. Volume therapy step 3: If there is an indication for red cell concentrates or coagulation factors, a differentiated application of blood and blood products should be performed.

[Anesthesia in thoracic surgery]. / Anästhesie in der Thoraxchirurgie.

Thoracic surgery represents a special challenge for anesthesia and requires a high level of human and material resources. Accurate knowledge of the pathophysiology is essential for selection of the anesthetic procedure, the separation of the lungs, monitoring and treatment of hemodynamics as well as for postoperative follow-up care. The increasing number of thoracic interventions and patients who are often suffering from complex diseases require close interdisciplinary cooperation between surgeons, anesthesiologists and intensive care specialists. In addition to the anesthetic techniques particular attention must be paid to the prevention of perioperative complications that can have a relevant effect on patient outcome. In particular hypoxemia during one-lung ventilation influences postoperative morbidity and mortality. Protective pulmonary ventilation strategies play an important role in prevention of postoperative acute lung injury.

[Costs of patient controlled analgesia in postoperative pain management in Germany]. / Kosten der patientenkontrollierten Analgesie (PCA) im Rahmen des postoperativen Schmerzmanagements in Deutschland.

PURPOSE: This systematic literature review was conducted to analyze the costs of postoperative patient controlled analgesia (PCA) in Germany. METHODS: The literature search comprised the search criteria "therapeutic procedure", "postoperative pain management", the routes of administration "intravenous PCA" (PCIA) and "epidural PCA" (PCEA), as well as their corresponding costs and economic analyses. RESULTS: Due to differences in indications, calculated costs and medical expenses it was not possible to compare the results from the respective studies. CONCLUSION: A critical examination of benefits and costs of therapeutic options in hospitals has become necessary with the implementation of the German DRG compensation system. This has created a substantial need for the optimization of resources and processes. There is an enormous demand for research on the costs for PCA in Germany. The identification of cost-driving factors is necessary to determine saving potentials and thereby develop new technologies for postoperative analgesia.

Added therapeutic value of memantine in the treatment of moderate to severe Alzheimer's disease.

When evaluating the added therapeutic value of a drug, evidence of greater overall benefit or at least an add-on benefit is increasingly being required. Therefore, cost-effectiveness in addition to clinical efficacy is an important consideration. The efficacy of a drug must be examined on the basis of clinical trials by measuring specific parameters that are affected by the drug (for example blood pressure with antihypertensive treatment). Today not only efficacy but also patient-relevant changes (patient benefits) must be demonstrated for a drug, often by measuring quality of life. In order to evaluate the benefit of monotherapy with the N-methyl-D-aspartate antagonist memantine in the management of moderate to severe Alzheimer's disease, a systematic literature review was conducted. The results showed a benefit for memantine in comparison with placebo in terms of a decrease in nursing care, a delay in care dependency and a delay in admission to nursing homes. In addition, an increase in quality of life has been observed.

[The situation of patients with dementia may be rectified by Ginkgo biloba. Results of a health services research study concerning the ability of patients with dementia, quality of life of the nursing family members and total treatment costs]. / Versorgungssituation von Demenzkranken kann durch Ginkgo biloba verbessert werden. Ergebnisse einer Studie zur Versorgungsforschung hinsichtlich der Leistungsfähigkeit der Demenzkranken, der Lebensqualität der Pflegenden und der Gesamtkosten der Behandlung.

UNLABELLED: BACKGROUND AND ISSSUES: Ginkgo biloba-extracts are often used in therapy of patients with dementia. In this study, benefit and structure of Ginkgo biloba-extract EGb 761 in treatment of patients with dementia was examined. PATIENTS AND METHODS: For the assessment of quality of life of care-taking relatives and patients as well as treatment costs were documented. The study was conducted as a non-randomised, two-armed cohort study with an open design for 683 slightly or moderately demented patients, aged between 65 and 80 years. Society's perspective was taken. Barthel-Index and MMST were also documented. Because of significant differences at inclusion of both cohorts, a matched-pairs-analysis and multiple regression analysis conducted. RESULTS: According to PLC a significant improvement in quality-of-life of care-taking relatives (p < 0.001) and patients (positive mood p = 0.018, negative mood p < 0.001) was only observed in the Ginkgo-cohort. Also Barthel-Index indicated an improvement in the Ginkgo-cohort (p < or = 0,001). MMST-scores increased significantly only in the Ginkgo-cohort (p < 0.001). Average total cost per patient amounted to 3.614,75 euro in the standard-cohort, whereas these costs per patient in the Ginkgo-cohort amounted to 3.031,78 euro (p = 0.067). Results were confirmed by matched-pairs-analysis. RESULTS: Ginkgo treatment has a valid place in caretaking structure of health services. Gingko attributes to a higher quality of life for both care-takers and patients, the progression of disease is slowed down and treatment costs are lower.

[Effectiveness of echinacin in therapy of chronic recurrent respiratory disease]. / Nutzenbewertung der Therapie chronisch rezidivierender Atemwegsinfekte mit Echinacin.

PURPOSE: Echinacea purpurea (echinacin) is frequently used in the therapy of chronic recurrent respiratory disease. The aim of this study was to show whether treatment of chronic recurrent respiratory disease with echinacin has a greater benefit in terms of effectiveness than therapy without an immunomodulator. MATERIALS AND METHODS: Frequency, duration of recurrence, resources used and patients' satisfaction was documented in order to assess benefit. In this prospective, non-randomised, multi-centre, nationwide, two-armed health services research study, data of 995 patients (782 echinacin-, 213 standard-cohort) with chronic recurrent respiratory disease were collected. The perspectives of statutory health insurance (SHI), patients and health policy were taken into consideration. RESULTS: The risk of falling ill was 2.3 fold higher and the duration of relapse 1.4 days more compared to the standard-cohort. There was a clinical and economical benefit from the therapy with echinacin for SHI and health policies. In contrast, patients experienced a greater financial burden. Average total costs per patient during the observation period of 3 months amounted to 238.35 in the standard-cohort and to 228.95 in the echinacin-cohort. Results of the intent-to-treat-analysis were reconfirmed in a per-protocol-analysis. CONCLUSION: This health services-research-study taking the therapy of chronic recurrent respiratory disease with echinacin as an example has shown that even non-prescription drugs can have clinical and economic benefits.

[Extracorporeal membrane oxygenation (ECMO) as cardiac assist device in pediatrics]. / Extrakorporale Membranoxygenierung (ECMO) als kardiales Unterstützungssystem in der Pädiatrie.

Extracorporeal membrane oxygenation (ECMO) is a common treatment for severe respiratory failure. However, ECMO can also be used as cardiac support. ECMO is the most common mechanical circulatory assist device in pediatrics, followed by pulsatile ventricular assist devices. Advantages are the simultaneous support of respiratory and hemodynamic functions and the fast bedside availability. The major disadvantage is the limited duration of therapy. The transthoracic connection of ECMO after cardiac failure in cardiothoracic surgery in childhood allows a controlled weaning on the intensive care unit. Weaning from ECMO is successful in about 45 to 80 % in cases of circulatory support; survival rates depend on patient selection, treatment protocol and indication. Bleeding problems, thromboembolic complications, hemolysis, infections, renal and neurologic complications are major problems.

[Amineptine and depressive symptoms, cardiovascular and ophthalmological acceptabilities (author's transl)]. / Points d'impact de l'amineptine sur les symptômes de la dépression. Acceptabilité cardio-vasculaire et ophtalmologique.

Amineptine is a new compound derived from the tricyclic antidepressants whose mechanism of action is mainly dopaminergic. In a clinical open trial, fifty patients suffering from neurotic, reactive and psychotic depression have been treated by 231 mg/day +/- 7 (mean +/- SEM) during 30 days. Results were assessed from Hamilton Rating Scale for depression before treatment and on D7, D14, D30. Cardiovascular and ophthalmological acceptability is discussed.

[The effect on breathing of flunitrazepam and benzoctamine as adjuvants in spinal anesthesia in broncho-pulmonary risk patients]. / Beeinflussung der Atmung durch Flunitrazepam und Benzoctamin als Adjuvantien zur Spinalanaesthesie bei bronchopulmonalen Risikopatienten.

The influence of intravenous Flunitrazepam (0.4-0.8 mg), Benzoctamine (10-20 mg) and Placebo (NaCl 0.9%) on pO2, pCO2, forced vital capacity, forced expiratory volume and peak flow were investigated in patients with reduced lung function undergoing orthopaedic surgery under spinal anaesthesia. Both drugs depress respiration: Flunitrazepam immediately, Benzoctamine about 15 min after administration. Both drugs reduce lung function in the postoperative period. They should be administered under careful observation of patients' respiration, administration of oxygen and only in special cases where sedation is necessary to reduce psychological stress. The advantage of regional anaesthesia in patients with high risk of postoperative pulmonary failure seems worth retaining compared to general anaesthesia.

[Experiences with continuous application of sedatives by infusion in patients with regional anaesthesia (author's transl)]. / Erfahrungen mit der kontinuierlichen Applikation von Sedativa per infusionem bei Plexusanästhesien.

The influence of frequently used sedatives--Diazepam, Flunitrazepam and Benzoctamin--on blood gases in studied in three groups of patients. The application isn't done as bolus injection but continuously by addition of the drugs in 500 ml physiological NaCl-Solution. In the Benzodiazepin groups the lung function is tested by different parameters. The results show no influence on blood gases nor lung function by this method. Therefore, the continuous application has obvious advantages versus bolus injection.

A double-blind multicentre trial comparing the efficacy and side-effects of mianserin and chlorimipramine in depressed in- and outpatients.

Mianserin (60 mg daily) was compared with chlorimipramine (150 mg daily) in the treatment of 145 depressed in- and outpatients in four centres. The trial was double-blind and fully randomized. Both drugs were effective antidepressants. No significant differences in efficacy could be demonstrated by means of the Hamilton rating scale for depression, the Beck self-rating scale or the clinical global impression, for both in- and outpatients. Hypotension, dry mouth and tremor increased significantly more in inpatients with chlorimipramine than with mianserin. At the end of treatment weight gain was increased significantly more in outpatients after treatment with mianserin. No differences could be demonstrated between the drugs for other side-effects.