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Macrophages play a dual role in regulating tumor progression. They can either reduce tumor growth by secreting antitumorigenic factors or promote tumor progression by secreting a variety of soluble factors. The purpose of this study was to define the monocyte/macrophage population prevalent in skeletal tumors, explore a mechanism employed in supporting prostate cancer (PCa) skeletal metastasis, and examine a novel therapeutic target. Phagocytic CD68+ cells were found to correlate with Gleason score in human PCa samples, and M2-like macrophages (F4/80+CD206+) were identified in PCa bone resident tumors in mice. Induced M2-like macrophages in vitro were more proficient at phagocytosis (efferocytosis) of apoptotic tumor cells than M1-like macrophages. Moreover, soluble factors released from efferocytic versus nonefferocytic macrophages increased PC-3 prostate cancer cell numbers in vitro. Trabectedin exposure reduced M2-like (F4/80+CD206+) macrophages in vivo. Trabectedin administration after PC-3 cell intracardiac inoculation reduced skeletal metastatic tumor growth. Preventative pretreatment with trabectedin 7 days prior to PC-3 cell injection resulted in reduced M2-like macrophages in the marrow and reduced skeletal tumor size. Together, these findings suggest that M2-like monocytes and macrophages promote PCa skeletal metastasis and that trabectedin represents a candidate therapeutic target.

Objectives To deliver a nationwide implementation of the ‘FIFA 11 for Health’ programme in Brazil and to compare the outcomes with results obtained previously in Sub-Saharan Africa. Method A cohort study among 3694 Brazilian children aged 9–12 years within 128 elementary schools situated in 12 cities in the five Regions of Brazil. The ‘FIFA 11 for Health’ programme contains 11 90 min sessions: the first 45 min serve to encourage physical activity through the development of football skills (Play Football) and the second 45 min provide a vehicle for delivering 10 health messages (Play Fair). We measured preintervention and postintervention health knowledge (29-item questionnaire) and the children9s evaluation of the programme (6-item questionnaire). Results Mean age of the children across the five Regions was 10.6 years (range 9.2–11.6). The mean preintervention health knowledge score for the five Regions was 60.2% (range 53.8–65.3%); the mean postintervention score was 78.6% (range 70.7–86.8%); thus the mean increase in health knowledge was 18.4% (range 13.6–29.1%). 91% of the children gave a positive evaluation for the programme (range across five Regions: 82.3–96.7%). Summary The study showed that the ‘FIFA 11 for Health’ programme, which was originally developed in English and translated into another language, was delivered successfully with results equivalent to those previously obtained in Sub-Saharan Africa. The programme was effective across the five Regions of Brazil.

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III.

SummaryIntroduction: This article is part of the Focus Theme of Methods of Information in Medicine on “Using Data from Ambient Assisted Living and Smart Homes in Electronic Health Records”.Background: Concepts of Ambient Assisted Living (AAL) support a long-term health monitoring and further medical and other services for multi-morbid patients with chronic diseases. In Germany many AAL and telemedical applications exist. Synergy effects by common agreements for essential application components and standards are not achieved.Objectives: It is necessary to define a communication architecture which is based on common definitions of communication scenarios, application components and communication standards.Methods: The development of a communication architecture requires different steps. To gain a reference model for the problem area different AAL and telemedicine projects were compared and relevant data elements were generalized. The derived reference model defines standardized communication links.Results: As a result the authors present an approach towards a reference architecture for AAL-communication. The focus of the architecture lays on the communication layer. The necessary application components are identified and a communication based on standards and their extensions is highlighted.Conclusion: The exchange of patient in -dividual events supported by an event classification model, raw and aggregated data from the personal home area over a tele-medicine center to health care providers is possible.

Exhausting physical exercise and insufficient nutritional intake impairing immunological and neuro-endocrine pathways are the most discussed issues in research on overtraining syndrome (OTS). Interestingly, depletion of the total body sodium (Na(+))-content which occurs in case of various diseases with completely different aetiologies is associated with a symptom pattern strikingly comparable to overreaching (OR) and/or OTS. The transient dilution based hyponatraemia gained attention due to its impact on reduced performance and the death of various endurance athletes. But the stepwise depletion of the total body (tissue) Na(+)-content is a completely different pathophysiology and is still relatively unknown. That is because depleted tissue Na(+)-content is hard to detect. The complex, dominant mechanisms for the maintenance of plasma homeostasis are concealing the Na(+)-depletion in the tissues quite successfully in a stage when symptoms already may be prominent. Furthermore, we are all programmed to think about sedentary people who are rather at risk to have a salt (Na(+)) intake which is far too high. But either, competitive top athletes and engaged recreational athletes have high losses of electrolytes with sweat and might be prone to a stepwise Na(+)-depletion. All the more because they also try to have a balanced, health sodium reduced diet. One person of our research group who is used to a rather low sodium-nutrition repeatedly experienced OR-(short term-OTS)-symptoms when training loads of recreational sport activities were increasing. Getting aware about identical symptoms between OR and total body Na(+)-depletion in another professional context the decision for a self experiment was settled. Under a given training protocol changing symptoms under low sodium-nutrition were recorded. When OR-like symptoms became prominent the training loads were maintained but stringent Na(+)-substitution was performed instead of the usually recommended resting period. As experienced before, typical symptoms such as sleeping disorders, harassed feeling, high diuresis, thirst and increasing blood pressure developed within 2 weeks with the increased training loads and the usual low Na(+)-nutrition. This was before plasma sodium decreased below the physiological range. High Na(+)-substitution instead of a resting period enabled the recovery from OR symptoms within some days. Out of various articles we choose and report some interesting further medical phenomenon where our hypothesis of Na(+)-depletion as a trigger mechanism might give new ideas for identifying pathophysiological mechanisms. The hypothesis: Tissue Na(+)-depletion triggers OR- and OTS- development via the renin-angiotensin-aldosterone system which initiate at first a stimulation and then exhaustion of the sympathetic system.

Hypertension is associated with high cardiovascular risk. Both hsCRP and NT-proBNP also have been associated with elevated cardiovascular risk, at least in the long term. Much less is known about the short-term changes in these markers, for example, in hypertensive emergencies. In 59 consecutive patients with hypertensive emergencies, hsCRP and NT-proBNP were measured at baseline and at days 3-4 and 7-10 after admission. All patients with hsCRP levels above 10 mg/l during the study were excluded due to possible infections. We found elevated levels of hsCRP at baseline with a significant decline on days 3-4 (day 0: median 2.53 mg/l, days 3-4: median 1.65 mg/l [p

Extracorporeal shockwave therapy (ESWT) is used in a number of indications in the medical field. A number of tendinopathies show good and excellent results due to evidence based medicine. The treatment of lateral epicondylitis is known to show conflicting results. This overview of the published RCT's on ESWT for lateral epicondylitis tries to show the reasons for this conflicting data-base and point out, why we think that this is still a main indication for extracorporeal shockwave therapy.

Extracorporeal shockwave therapy (ESWT) has gained acceptance in the medical field and in the treatment of non-unions and delayed bone healing. ESWT has been used effectively for many years as a noninvasive surgical procedure. The idea of treating Osteochondritis dissecans of knee and talus arose in the middle of the 1990's. OCD is known as a pre-arthritic factor in the long-term and still there is no consistent treatment. In the literature there is still only a small number of publications but international societies for shockwave treatment are convinced that ESWT on OCD shows to be an effective and safe method in the treatment of OCD in the early stages. We want to summarize the actual data on the treatment of OCD by ESWT.

Background: There is a national shortage of psychiatrists, and according to nationally available data, it is projected to get worse. Locum tenens psychiatry and telepsychiatry are two ways to fill the shortages of psychiatric providers that exist in many areas in the United States (U.S.). Employment and salary data in these areas can be used to illuminate current trends and anticipate future solutions to the problem of increasing demand for, and decreasing supply of, psychiatrists in the U.S. Methods: A search was conducted of the literature and relevant websites including PubMed, Google Scholar, www.google.com, and information obtained from locum tenens and telepsychiatry organizations. Results: There is a dearth of data on the use of locum tenens in the field of psychiatry with little available prior to 2000 and few published studies since then. The majority of the data available is survey data from commercial entities. This data shows trends toward increasing demand for psychiatry along with increasing salaries and indicates the utilization of telepsychiatry and locum tenens telepsychiatry are increasing. The published academic data that is available shows that while locum tenens psychiatry is slightly inferior to routine psychiatric care, telepsychiatry is generally equivalent to face-to-face care. Conclusion: One can anticipate that as the national shortage of psychiatrists is expected to accelerate, use of both locum tenens and telepsychiatry may also continue to increase. Telepsychiatry offers several possible advantages including lower cost, longer term services, quality of care, and models that can extend psychiatric services. If current trends continue, systems that demand face-to-face psychiatry may find themselves paying higher fees for locum tenens psychiatrists, while others may employ psychiatrists more efficiently with telepsychiatry.

The cyclopentapeptide FC131 (cyclo(-L-Arg(1) -L-Arg(2) -L-2-Nal(3) -Gly(4) -D-Tyr(5) -)) is an antagonist at the CXC chemokine receptor CXCR4, which plays a role in human immunodeficiency virus infection, cancer and stem cell recruitment. Binding modes for FC131 in CXCR4 have previously been suggested based on molecular docking guided by structure-activity relationship (SAR) data; however, none of these have been verified by in vitro experiments.Heterologous (125) I-12G5-competition binding and functional assays (inhibition of CXCL12-mediated activation) of FC131 and three analogues were performed on wild-type CXCR4 and 25 receptor mutants. Computational modelling was used to rationalize the experimental data.The Arg(2) and 2-Nal(3) side chains of FC131 interact with residues in TM-3 (His(113) , Asp(171) ) and TM-5 (hydrophobic pocket) respectively. Arg(1) forms charge-charge interactions with Asp(187) in ECL-2, while D-Tyr(5) points to the extracellular side of CXCR4. Furthermore, the backbone of FC131 interacts with the chemokine receptor-conserved Glu(288) via two water molecules. Intriguingly, Tyr(116) and Glu(288) form a H-bond in CXCR4 crystal structures and mutation of either residue to Ala abolishes CXCR4 activity.Ligand modification, receptor mutagenesis and computational modelling approaches were used to identify the binding mode of FC131 in CXCR4, which was in agreement with binding modes suggested from previous SAR studies. Furthermore, insights into the mechanism for CXCR4 activation by CXCL12 were gained. The combined findings will facilitate future design of novel CXCR4 antagonists.

A conserved amino acid within a protein family indicates a significance of the residue. In the centre of transmembrane helix (TM)-5, position V:13/5.47, an aromatic amino acid is conserved among class A 7TM receptors. However, in 37% of chemokine receptors - a subgroup of 7TM receptors - it is a leucine indicating an altered function. Here, we describe the significance of this position and its possible interaction with TM-3 for CCR5 activity.The effects of [L203F]-CCR5 in TM-5 (position V:13/5.47), [I116A]-CCR5 in TM-3 (III:16/3.40) and [L203F;G286F]-CCR5 (V:13/5.47;VII:09/7.42) were determined in G-protein- and β-arrestin-coupled signalling. Computational modelling monitored changes in amino acid conformation.[L203F]-CCR5 increased the basal level of G-protein coupling (20-70% of Emax ) and β-arrestin recruitment (50% of Emax ) with a threefold increase in agonist potency. In silico, [I116A]-CCR5 switched χ1-angle in [L203F]-CCR5. Furthermore, [I116A]-CCR5 was constitutively active to a similar degree as [L203F]-CCR5. Tyr(244) in TM-6 (VI:09/6.44) moved towards TM-5 in silico, consistent with its previously shown function for CCR5 activation. On [L203F;G286F]-CCR5 the antagonist aplaviroc was converted to a superagonist.The results imply that an aromatic amino acid in the centre of TM-5 controls the level of receptor activity. Furthermore, Ile(116) acts as a gate for the movement of Tyr(244) towards TM-5 in the active state, a mechanism proposed previously for the β2 -adrenoceptor. The results provide an understanding of chemokine receptor function and thereby information for the development of biased and non-biased antagonists and inverse agonists.

Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas.Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy.Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found.All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.

This study investigates the effects of the multikinase inhibitor axitinib on the expression of vascular endothelial growth factor (VEGF) receptors 1/2 (VEGFR-1/2) and platelet-derived growth factor (PDGF) receptor beta (PDGFR-β), hypoxia-induced increased tissue permeability, occludin, zonula occludens protein 1 (ZO-1), VEGF-A, and PDGF expression of human retinal pigment epithelial (RPE) cells and human umbilical vein endothelial cells (HUVECs). Primary human RPE cells and HUVECs were exposed to hypoxia and axitinib. Viability of cells, tissue permeability, and expression of occludin, ZO-1, VEGF, PDGF, VEGFR-1/2 and PDGFR-β, and their mRNAs, were investigated by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Treatment with axitinib reduced expression of VEGFR-1/2 and PDGFR-β. Hypoxia decreased cell viability, occludin, and ZO-1 expression and increased tissue permeability, expression, and secretion of VEGF and PDGF. Axitinib significantly reduced hypoxia-induced effects on HUVEC and RPE cells. Our in vitro results suggest that axitinib may have promising properties as a potential treatment for diabetic macular edema.

Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline.Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis.Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions.This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation.

Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor A (VEGF) is the main target of current antiangiogenic treatment strategies for AMD. Previous reports indicated that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of VEGF and its receptors VEGFR1 and 2 in human retinal pigment epithelial (RPE) cells.The effects of sorafenib on VEGFR1 and 2 expression of primary human RPE cells was investigated by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting. In addition, RPE cells were exposed to white light and incubated with sorafenib. Viability, expression of VEGF and its mRNA were determined by RT-PCR, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assays.Sorafenib reduced VEGFR1 and 2 expression of RPE cells. Light exposure decreased cell viability and increased expression and secretion of VEGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml.The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.

In our Tissue Engineering group a 3D in vitro model for rheumatoid Arthritis (in vitro pannus) was established with the aim to develop a standardized drug-screening test to analyze the effects of drugs and different biological substances. The advanced model consists of chondrocyte pellet cultures interacting with rheumatoid arthritis (RA) synovial cell cultures. To establish interactive 3D co-cultures defined rheumatoid arthritis synovial cell populations were centrifuged directly on chondrocyte pellet cultures. Histochemical stainings during time of co-culture revealed obvious invasion by RA synovial cell populations into the chondrocyte matrix. Gene expression analysis showed a downregulation of collagen type II expression in chondrocytes within 2 weeks after co-culture with RA synovial cells. Those interactive co-cultures allow the study of single cell populations as well as the cellular interactions in this system under in vitro conditions. Thus, the established co-culture model may be suitable for routine screening tests, which can be useful in supplementing animal experiments in basic research and drug testing.

There is a growing body of evidence suggesting that calcium channel blockers (CCB) exert beneficial effects on kidney transplant survival. However, it is not completely understood if these agents act independently of blood-pressure reduction. In the present study, the 5-yr follow-up of 45 kidney transplant recipients receiving CCB during the 60-month follow-up period was compared to that of recipients with lower blood pressure and an antihypertensive treatment without CCB. During the whole follow-up, systolic (127.4 +/- 2.5 vs. 139.4 +/- 2.1 mmHg, p0.05) as well as diastolic blood pressure (78.8 +/- 1.1 vs. 84.8 +/- 1.8 mmHg, p0.05) was higher in the group receiving CCB. Moreover, in CCB-treated recipients, a significant (p0.05) higher increase in proteinuria was detected (from 759 +/- 120 to 1690 +/- 359 mg/24 h vs. 180 +/- 45 to 340 +/- 45 mg/24 h). Despite higher blood pressure and higher proteinuria, the increase in serum creatinine in the group of CCB-treated recipients was significantly lower (0.01 mg/dL/month) in comparison to that of the controls (0.02 mg/dL/month, p0.05). Moreover, the 5-yr transplant survival was significantly higher in CCB-treated recipients (62.3 vs. 31.8%, p0.05). The results of the present study further support the beneficial effects of CCB in kidney transplant recipients, which are independent of blood-pressure reduction.

The mortality rate for the advanced adult respiratory distress syndrome is still high. Nevertheless there are recent publications showing decreasing incidence and an improving survival rate. This is due to early diagnosis as well as differentiated treatment concepts. The use of special therapy methods including extracorporal gas exchange is only possible at specialized centres. This raises the question as to the right timing of the transfer of those ARDS-patients, whose lungs cannot be cured by the therapy standards practiced locally. In a prospective study, all requests for transfer were noted over a period of 36 months (1992 to 1994) and analyzed by a hospital with a special ward for ARDS. In a total of 469 patients the most prominent predisposing diseases were community-acquired pneumonia (26.3%), followed by multiple trauma (24.4%), the postoperative conditions of systemic inflammatory response syndrome (SIRS) or sepsis (21.3%), bronchopulmonary aspiration (5.8%), and status asthmaticus (2.6%). With a mean preventilation time of 9.5 +/- 9 days and a mean ventilatory peak pressure of 39 +/- 8 cm H2O there was a mean oxygenation index (Horrowitz Index) of 95 (+/- 40) mm Hg. The mean Smith and Gordon Ventilator Score was 82.3 (+/- 12.8) and the mean PIF rate (Benzer Score) 12 (+/- 8.6), 121 out of 469 patients were transferred for further specialized therapy. 75 patients were treated on a conventional basis and 46 patients had to be treated with extracorporal lung assistance (ELA) because conventional treatment failed. The mortality rate was 22.3% altogether, in the group with the conventional treatment 16.0% and 32.6% in the group with ELA. As there are no generally accepted guidelines for the transfer of patients with ARDS to specialized centres, an indication for such a transfer must be established taking into consideration the individual patient history. Very early contact with the specialized centre of choice is recommended.

FIGURE 1. Posteroanterior chest roentgenogram illtmstrating wellcircumscribed homogeneous right tmpper lobe cystic lesion. deferred while a second opinion was obtained. The patient felt well and specifically denied fever, chills, chest pain, sputum production, hemoptysis, o)r previous episodes of pneumonia. She had no known exposure to tuberculosis and no prior history of surgery. She was receiving no medications and did not smoke. At the time of presentation, she was a sophomore in college and regtilarly enjoyed aerobics. There was no history of travel outside the United States. The findings from physical examination were completely unremarkable. The chest x-ray film showed a well-circtiniscribed right tipper lobe cystic structure (Fig 1), and the CT scan showed an homogeneous mass (Hounsfield number of3O) with an apparent rind (Fig 2). Laboratory studies were unrevealing, with a no)rmal white blood cell count and differential cell count. The mass remained unchanged during four months offollow-up, and subsequently the patient was admitted for thoracotomy.

A 44-year-old patient with 24 kg reduction of body weight within three years due to recurrent diarrhea was admitted to the hospital. Physical findings of the patient were not remarkable, except for hypesthesia and hypalgesia of the front of the tibia and of the lower legs. Laboratory as well as endoscopic and functional examinations of the gastrointestinal tract did not reveal any remarkable finding. Infectious origins of the disease were excluded. A histological examination of a rectum specimen yielded amyloid deposits in the submucosa of the rectum. In the family history of the patient, relatives with liver and gastrointestinal diseases due to amyloidosis were detected. Amyloid deposits and the positive family history of the patient led to the diagnosis of a gastrointestinal manifestation of familial amyloidosis.

To define differences of specifity and sensitivity between a solid phase- and a gel centrifugation test for detection of irregular erythrocyte antibodies.3052 blood samples were screened for erythrocyte antibodies (AB) by gel centrifugation [ID-System, (ID) 37 degrees C Bromelin and indirect antiglobulin test with LISS (IAT)] and a solid phase antiglobulin test [Capture-R Ready Screen (CR)] in a prospective study. Identical test cells were used as immobilized monolayer in CR and as 1%-suspension in ID. Additionally, 42 sera with antibodies reacting in both tests were titered geometrically in both techniques.In 79 (2.6%) of all sera tested, irregular erythrocyte antibodies were detected. 64 (81%) of these positive sera were detected by both tests, 73 (92.3%) by ID and 70 (88.4%) by CR. 6 sera with AB (7.6%) were positive only with CR (1 Ce, 1 E, 1 Leb, 1 C, 1 D, 1 Cob) and 9 (11.4%) only with ID (4 Lea, 1 Fya, 1 C, 2 P1, 1 D). Seven AB solely detected in ID only reacted in the bromelin test, besides an anti-Fya, which was an IgM antibody. The titration of IgG antibodies showed a slightly higher sensitivity of the CR (less than one titre step). The ID showed clearly more unspecific reactions (1.1%) than the CR (0.5%).The antibody screening with the ID proved to detect more AB than the CR (mainly due to certainly irrelevant "enzyme only" AB). On the other hand, relevant IgG AB were detected more sensitive by the CR. Unspecific reactions appeared clearly more often in ID, predominantly when using the bromelin test. Missing a strong IgM anti-Fya in the CR is certainly a concern because of its assumed haemolytic activity. Therefore CR for antibody screening should always be combined with a method for crossmatching that safely detects IgM antibodies which are relevant for transfusion.

Inhalation therapy with the use of helium-oxygen has been advocated in the treatment of upper airway obstruction due to various causes. The therapeutic effect is secondary to a decrease in turbulent flow and airway resistance in areas of obstruction. We present a patient with acute respiratory failure secondary to upper airway obstruction caused by a tumor involving the distal trachea and proximal left mainstem bronchus. Despite assistance with a mechanical ventilator, the patient remained tachypneic and hypercarbic. Following institution of helium therapy, the patient became less short of breath and her carbon dioxide returned to a normal level. She was later weaned from mechanical ventilation and discharged from the hospital.

Two patients with severe pulmonary blastomycosis were treated with ketoconazole. One patient developed disseminated disease while receiving this drug. After responding to incomplete treatment with amphotericin B, this patient relapsed while continuing ketoconazole therapy. The second patient failed to respond to ketoconazole and died shortly after treatment with amphotericin B was instituted. We conclude that it is dangerous to use ketoconazole as initial treatment in patients with severe forms of blastomycosis. Death, relapse, and prolonged morbidity may be the result. In such cases, amphotericin B is still the drug of first choice despite its toxicity, inconvenience, and expense of administration.

In 896 patients from a low-iodine area the results of the radioimmununological triiodothyronine estimations in plasma were compared with the clinical and radioisotope findings of thyroid function. It was superior to the total thyroxine estimation (T4-test) in the differential diagnosis of hyperthyroidism. In euthyroid goitre the mean triiodothyronine concentration was significantly higher than in normal persons whereas the plasma thyroxine levels at the same time were significantly lower. Only in (primary) hypothyroidism is the triiodothyronine estimation diagnostically less important than the T4-test. In summary, the radioimmunochemical method permits a clearly more precise evaluation of thyroid function even in areas of endemic goitre.

Heavy water (D2O) is able to activate or to inhibit biological systems and thus influences metabolism and functions of tissues and organs. On the basis of results obtained in preservation experiments performed on various organs, the effects of D2O on the functions of human platelets (retraction, spreading, aggregation induced by adrenaline, ADP and collagen) have been investigated. The effects of D2O, involving changes of membrane receptor conformation, binding strength of substances to their specific receptors, pH-values or enzyme activities, resulted in a significant decrease of ADP- and collagen-induced aggregation, while adrenaline-induced aggregation was significantly increased at the same D2O concentration. Retraction in the presence of D2O was significantly inhibited in a dose-related manner, while spreading was diminished, but not fully inhibited even by highest concentrations of D2O (95%).

In recent investigations it was found that ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7 (1-piperazinyl)-3-fiquinoline-carboxylic acid, Ciprobay) in concentrations similar to maximal levels obtained in the serum of patients with normal renal function after application of therapeutic doses and 4- to 5fold such concentrations does not influence aggregation induced by epinephrine and collagen in platelet rich plasma of healthy subjects. Because in literature there are several reports about disturbances of platelet aggregation in patients with renal failure treated with antibiotics and because renal failure often is accompanied by defect platelet function the effect of ciprofloxacin on epinephrine and collagen induced aggregation was studied in platelet rich plasma of patients with chronic renal failure undergoing dialysis. Compared to platelets from patients with renal failure which had been incubated with saline instead of ciprofloxacin, patients platelets under the influence of ciprofloxacin did not show any significant differences. From this we conclude that the defect which may be present in platelets of patients with chronic renal failure is not further increased by ciprofloxacin.

Concentrations of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin; designated tradename: Ciprobay) similar to maximal levels obtained in the serum of patients with intact renal function after application of therapeutic doses and 4- to 5-fold such concentrations do not influence epinephrine- or collagen-induced aggregation. 100 micrograms/ml ciprofloxacin, corresponding to the 20 fold maximal serum level of patients with intact renal function, does not influence aggregation induced by 2 micrograms/ml collagen as regards degree and kinetics of aggregation, while aggregation induced by 0.2 micrograms/ml collagen is significantly reduce. Aggregation induced by 1, 2 and 4 mumol/l epinephrine is also reduced significantly by 100 micrograms/ml ciprofloxacin. Changes brought about by high doses of ciprofloxacin still occur within the normal range. It is therefore concluded from this study that the hemostatic function of the platelets is not influenced in a clinically relevant manner by ciprofloxacin. Regarding the effect on platelet aggregation ciprofloxacin corresponds to the structurally related pipemidic acid.

Concentrations of pipemidic acid (Deblaston) similar to maximal levels obtained in the serum of patients with intact renal function after application of therapeutic doses do not influence epinephrine (adrenaline)- or collagen-induced aggregation in vitro. With 20 micrograms/ml pipemidic acid, corresponding 4- to 5-fold maximal serum levels epinephrine-induced aggregation is reduced significantly, while aggregation by collagen is not affected. A significant reduction of epinephrine-induced aggregation as well as of collagen-induced aggregation is brought about only with doses of pipemidic acid as high as 100 micrograms/ml. But these changes still occur within the normal range. Therefore we conclude from our study, that platelet aggregation is not affected in a clinically relevant manner by pipemidic acid.