Real-time non-adiabatic dynamics in the one-dimensional Holstein model: Trajectory-based vs exact methods.

We benchmark a set of quantum-chemistry methods, including multitrajectory Ehrenfest, fewest-switches surface-hopping, and multiconfigurational-Ehrenfest dynamics, against exact quantum-many-body techniques by studying real-time dynamics in the Holstein model. This is a paradigmatic model in condensed matter theory incorporating a local coupling of electrons to Einstein phonons. For the two-site and three-site Holstein model, we discuss the exact and quantum-chemistry methods in terms of the Born-Huang formalism, covering different initial states, which either start on a single Born-Oppenheimer surface, or with the electron localized to a single site. For extended systems with up to 51 sites, we address both the physics of single Holstein polarons and the dynamics of charge-density waves at finite electron densities. For these extended systems, we compare the quantum-chemistry methods to exact dynamics obtained from time-dependent density matrix renormalization group calculations with local basis optimization (DMRG-LBO). We observe that the multitrajectory Ehrenfest method, in general, only captures the ultrashort time dynamics accurately. In contrast, the surface-hopping method with suitable corrections provides a much better description of the long-time behavior but struggles with the short-time description of coherences between different Born-Oppenheimer states. We show that the multiconfigurational Ehrenfest method yields a significant improvement over the multitrajectory Ehrenfest method and can be converged to the exact results in small systems with moderate computational efforts. We further observe that for extended systems, this convergence is slower with respect to the number of configurations. Our benchmark study demonstrates that DMRG-LBO is a useful tool for assessing the quality of the quantum-chemistry methods.

Retrospective 8-year analysis of negative pressure wound therapy in dermatosurgery: a single-centre experience.

BACKGROUND: Negative pressure wound therapy (NPWT) is an established treatment modality in dermatologic surgery, but proof of evidence for efficacy is inconclusive. PURPOSE: To evaluate patient characteristics, treatment modalities and outcomes in a single dermatosurgery centre with NPWT applied over chronic and acute surgical wounds. METHODS: Of all surgical patients between 2008 and 2015, we selected those who were treated and hospitalized due to NPWT for treatment of acute and chronic wounds. The medical records of 188 patients were retrospectively evaluated and statistically calculated. RESULTS: Method of surgical defect closure depends significantly on localization of the surgical defect, cardiovascular comorbidity and age. Hence, outcome depends significantly on the surgical situation that indexes NPWT, the underlying diagnosis and the vacuum system used, but is not associated with distinct treatment modalities or gender of the patients. Hospitalization significantly depends on the vacuum system used, surgical situation that indexes NPWT and underlying diagnoses. CONCLUSION: NPWT has a fixed role in distinct, well-defined clinical indications in dermatosurgery as the treatment of acute surgical wounds, fixation of skin grafts and treatment of skin substitutes, as well as an important treatment option for refractory, superinfected chronic wounds in dermatologic patients.

Presentation of a Sedation Standard Using the Example of Transesophageal Echocardiographies (TEE) in Pediatric Outpatients.

Introduction Most pediatric patients require deep sedation for a TEE examination. We analyzed the data of our sedation protocols relating to all outpatient TEEs in patients under 18 years of age for the year 2011. On the basis of the data records of a total of 40 patients, we will describe our standard and compare it with the findings of the international literature. Material and Methods In a retrospective analysis, we inspected our sedation protocols in terms of patient-related data, vital parameters, drug applications, occurring complications and necessary interventions as well as nausea and vomiting during the post-sedative monitoring phase. Results In line with our standard, we applied atropine, midazolam, S-ketamine and propofol; complications occurred in 5 patients. They could be handled using simple measures. With regard to the vital parameters, no severe complications occurred. Dizziness was observed in 4 patients during the recovery phase; one patient complained about nausea and vomiting during the first fluid intake. All patients could be discharged 4 h after the termination of sedation. Conclusion Our standard is a practicable and safe procedure for preforming TEE examinations in pediatric outpatients.

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

BACKGROUND: Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered. METHOD: The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. RESULTS: Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. CONCLUSIONS: Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.

[Prevalence and risk factors of drug induced liver disease: a survey based study in pharmacies]. / Häufigkeit und Risikofaktoren medikamentös-toxischer Leberschäden: eine umfragebasierte Studie in Apotheken.

AIM: The reported incidence of drug-induced liver injury (DILI) ranges from 1 in 10,000 to 1 in 100,000 patients for most drugs, but the true incidence is expected to be much higher. Several risk factors for DILI susceptibility have been suggested, however there is insufficient data to define an individual risk profile. Therefore it was our aim to study the prevalence of DILI and potential risk factors within adult pharmacy customers in Germany. METHODS: We conducted two 6 week-survey studies in 30 pharmacies in 2011 and 2012, respectively, using a newly developed questionnaire comprising questions on demography, (liver) diseases, liver enzyme activities, and drug history. In each study, anonymized questionnaires were presented to non-selected adult customers taking (non-)prescription drugs. RESULTS: Combining the datasets from the 2011 and 2012 surveys, in total 1098 questionnaires were evaluated (mean age 57.7 ±â€Š17.1 years; 62.6 % females, return rate 15.25 %). Overall, 141 individuals (12.8 %) reported elevated liver enzymes due to drugs, in 65 cases (5.9 %) the medication had to be stopped, and 20 customers (1.8 %) reported that they had been admitted to hospital due to DILI. Compared to individuals without adverse hepatic drug reactions (n = 957), the 141 persons with potential DILI presented more often the following risk factors in multivariate analysis: chronic liver disease (14.4 % vs. 2.4 %, odds ratio [OR] 4.2, 95 % confidence interval [CI] 2.0 - 9.0), chronic renal insufficiency (20.0 vs. 6.8 %, OR 2.2, 95 % CI 1.3 - 3.7), diabetes (34 vs. 15.3 %, OR 2.0, 95 % CI 1.3 - 3.2), family history of chronic liver disease (19.9 vs. 7.7 %, OR 2.1, 95 % CI 1.2 - 3.6), and continuous drug intake for more than 5 years (80.9 vs. 59.3 %, OR 2.1, 95 % CI 1.3 - 3.5). CONCLUSION: These studies show an unexpected high prevalence of DILI in pharmacy customers and identify multiple potential risk factors.

[Lumbar back pain in patients with Parkinson's disease]. / Lendenwirbelsäulenschmerzen bei Patienten mit Morbus Parkinson.

BACKGROUND: Lumbar back pain is a frequent symptom in patients with advanced Parkinson's disease. We examined the effect of modification of the dopaminergic medication, x-ray-controlled lumbar spine injections and analgesics combined with physiotherapy. METHODS: The data from 50 patients with Parkinson's disease and lumbar back pain were retrospectively analyzed. A structured L-dopa test was performed with all patients, whereby the pain intensity and mobility were monitored before and after the administration of L-dopa. Dopaminergic medication was adjusted in patients who reported either a reduction in pain intensity (> 20%) and/or an improvement of measured mobility and X-ray controlled lumbar spine injections were conducted in patients who reported persistent pain. Analgesics were introduced or dosages were raised in patients who had already received lumbar spine injections and continued to report pain. All patients participated in a daily physiotherapy program. RESULTS: In the L-dopa test an improvement of mobility could be demonstrated in 40 patients and reduced pain intensity in 21 patients. In 37 patients with a positive L-dopa test the dopaminergic medication was adjusted. In 12 of these patients (24%) a decrease of pain intensity could be observed. Due to persisting back pain in 30 patients lumbar spine injections were conducted. Of these patients 17 (34%) had pain improvement. In 20 patients analgesics were applied and induced pain relief in 15 patients (30%). Overall 44 patients (88%) had an improvement in pain. DISCUSSION: Even in cases of severe lumbar spine pathology adjustment of dopaminergic medication should be tested in all patients with Parkinson's disease and lumbar back pain. In patients with persistent pain facet joint injections as well as analgesics may be helpful and should be tested according to the predominant pain characteristics.

Same Site Recurrence is More Frequent After Endovenous Laser Ablation Compared with High Ligation and Stripping of the Great Saphenous Vein: 5 year Results of a Randomized Clinical Trial (RELACS Study).

OBJECTIVE: To compare the long-term clinical efficacy of endovenous laser ablation (EVLA) with high ligation and stripping (HLS) as standard treatment for great saphenous vein (GSV) incompetence. DESIGN: Investigator initiated two centre randomized controlled trial with 5 year follow up. MATERIALS AND METHODS: Interventions were performed on ambulatory and hospitalized patients at two vein centres, a university dermatology department (EVLA) and a specialized vein clinic (HLS). Four hundred patients suffering from GSV incompetence were assigned to EVLA or HLS of the GSV. One hundred and eighty five and 161 patients (=limbs), respectively, were treated per protocol. Main outcome measures were clinically recurrent varicose veins after surgery (REVAS classification, primary study objective), Duplex detected saphenofemoral recurrence, clinical venous severity scoring (Homburg Varicose Vein Severity Score), quality of life (Chronic Venous Insufficiency Questionnaire 2), side effects, and patient satisfaction 5 years after treatment. RESULTS: Two hundred and eighty one legs (81% of the study population) were evaluated with a median follow up of 60.4 (EVLA) and 60.7 months (HLS). Overall, REVAS was similarly observed in both groups: 45% (EVLA) and 54% (HLS), p = .152. Patients of the EVLA group showed significantly more clinical recurrences in the operated region (REVAS: same site): 18% vs. 5%, p = .002. In contrast, more different site recurrences were observed in the HLS group: 50% vs. 31%, p = .002. Duplex detected saphenofemoral refluxes occurred more frequently after EVLA: 28% vs. 5%, p < .001. Both treatments improved disease severity and quality of life without any difference. CONCLUSIONS: EVLA and HLS are comparably effective concerning overall REVAS, improvement of disease severity, and quality of life. In terms of same site clinical recurrence and saphenofemoral refluxes, HLS is superior to EVLA 5 years after treatment. CLINICAL TRIAL REGISTRATION: ISRCTN18322872.

Obesity in regional anesthesia--a risk factor for peripheral catheter-related infections.

BACKGROUND: Obesity is believed to increase the risk of surgical site infections and possibly increase the risk of catheter-related infections in regional anesthesia. We, therefore, analyzed the influence of obesity on catheter-related infections defined within a national registry for regional anesthesia. METHODS: The German Network for Regional Anesthesia database with 25 participating clinical centers was analyzed between 2007 and 2012. Exactly, 28,249 cases (13,239 peripheral nerve and 15,010 neuraxial blocks) of patients ≥ 14 years were grouped in I: underweight (BMI 13.2-18.49 kg/m(2) , n = 597), II: normal weight (BMI 18.5-24.9 kg/m(2) , n = 9272), III: overweight (BMI 25.0-29.9 kg/m(2) , n = 10,632), and IV: obese (BMI 30.0-70.3 kg/m(2) , n = 7,744). The analysis focused on peripheral and neuraxial catheter-related infections. Differences between the groups were tested with non-parametric ANOVA and chi-square (P < 0.05). Binary logistic regression was used to compare obese, overweight, or underweight patients with normal weight patients. Odds ratios (OR and 95% confidence interval) were calculated and adjusted for potential confounders. RESULTS: Confounders with significant influence on the risk for catheter-related infections were gender, age, ASA score, diabetes, preoperative infection, multiple skin puncture, and prolonged catheter use. The incidence (normal weight: 2.1%, obese: 3.6%; P < 0.001) and the risk of peripheral catheter-related infection was increased in obese compared to normal weight patients [adjusted OR: 1.69 (1.25-2.28); P < 0.001]. In neuraxial sites, the incidence of catheter-related infections differed significantly between normal weight and obese patients (normal weight: 3.2%, obese: 2.3%; P = 0.01), whereas the risk was comparable [adjusted OR: 0.95 (0.71-1.28); P = 0.92]. CONCLUSION: This retrospective cohort study suggests that obesity is an independent risk factor for peripheral, but not neuraxial, catheter-related infections.

Pretreatment for bilateral nephroblastomatosis is an independent risk factor for progressive disease in patients with stage V nephroblastoma.

BACKGROUND: Treatment of stage V nephroblastoma is less established and more complex than in unilateral nephroblastoma. METHODS: Retrospective analysis of 121 consecutive patients with stage V nephroblastoma registered from January 1989 to May 2005. Registration, prospective data collection and treatment were carried out within the framework of 3 consecutive SIOP/GPOH-nephroblastoma-trials. RESULTS: 19 patients had metastasis and 29 syndromes at diagnosis. 13 patients had been pretreated for bilateral nephroblastomatosis. 1 patient was not treated and 17 patients had upfront surgery. Preoperative treatment duration ranged from 1-12 weeks (n=103). 1-3 preoperative treatment-cycles resulted in average tumor-volume-reduction of 45%. 1 patient underwent bilateral nephrectomy. 52% of the patients had 2 functioning kidneys after the end of treatment. 20 patients had died after mean follow-up of 8.6 years. 5y-Progression-Free (PFS) and Overall-Survival (OS) were excellent for patients having a localized disease without pretreatment for nephroblastomatosis (5yPFS/OS: 80±4%/93±3%). Metastasis at diagnosis (51±12%/56±12%; p=0.003) and pretreatment for nephroblastomatosis (37±14%/67±13%; p<0.001) were associated with significantly poorer outcome. Cox-regression analysis revealed an independent influence of pretreatment for nephroblastomatosis, metastasis and syndromes on PFS. The latter 2 as well as anaplasia and age (<2 years or >3 years) had an independent influence on OS. CONCLUSIONS: Pretreatment for nephroblastomatosis, metastasis and syndromes are independent risk factors. 1-3 preoperative treatment-cycles are sufficient to achieve save nephron-sparing-surgery in most patients.

Temporal and spatial migration pattern of the subchondral bone plate in a rabbit osteochondral defect model.

OBJECTIVE: Upward migration of the subchondral bone plate is associated with osteochondral repair. The aim of this study was to quantitatively monitor the sequence of subchondral bone plate advancement in a lapine model of spontaneous osteochondral repair over a 1-year period and to correlate these findings with articular cartilage repair. DESIGN: Standardized cylindrical osteochondral defects were created in the rabbit trochlear groove. Subchondral bone reconstitution patterns were identified at five time points. Migration of the subchondral bone plate and areas occupied by osseous repair tissue were determined by histomorphometrical analysis. Tidemark formation and overall cartilage repair were correlated with the histomorphometrical parameters of the subchondral bone. RESULTS: The subchondral bone reconstitution pattern was cylindrical at 3 weeks, infundibuliform at 6 weeks, plane at 4 and 6 months, and hypertrophic after 1 year. At this late time point, the osteochondral junction advanced 0.19 [95% confidence intervals (CI) 0.10-0.30] mm above its original level. Overall articular cartilage repair was significantly improved by 4 and 6 months but degraded after 1 year. Subchondral bone plate migration correlated with tidemark formation (r = 0.47; P < 0.0001), but not with the overall score of the repair cartilage (r = 0.11; P > 0.44). CONCLUSIONS: The subchondral bone plate is reconstituted in a distinct chronological order. The lack of correlation suggests that articular cartilage repair and subchondral bone reconstitution proceed at a different pace and that the advancement of the subchondral bone plate is not responsible for the diminished articular cartilage repair in this model.

Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral antidiabetic agents that hold the potential of slowing the progress of type 2 diabetes mellitus. Their long-term safety is still a subject of debate. A systematic review of randomized, controlled trials was undertaken to comprehensively profile the safety of chronic treatment of type 2 diabetes mellitus with DPP-4 inhibitors. We searched data sources including MEDLINE, CENTRAL, publishers' and manufacturers' databases. Eligible trials were double-blind, randomized, placebo or active-controlled trials with ≥18 weeks duration in patients with type 2 diabetes reporting safety outcomes. Meta-analysis was performed separately for trials in which the control group received placebo (44 studies), another gliptin (3 studies) and any other antidiabetic drug (20 studies). Risk ratios with 95% confidence intervals were computed using a Mantel-Haenszel fixed-effect model for general safety outcomes, hypoglycaemia and adverse events by system organ class. Of 307 publications retrieved, 67 randomized, controlled trials met the eligibility criteria and were included in this review (4 alogliptin, 8 linagliptin, 8 saxagliptin, 20 sitagliptin, and 27 vildagliptin trials). Adverse events with gliptin treatment were at placebo level (relative risk (RR) 1.02 [0.99, 1.04]). No increased risk of infections was detectable (RR 0.98 [0.93, 1.05] compared to placebo and 1.02 [0.97, 1.07] compared to other antidiabetic drugs). Asthenia (RR 1.57 [1.09, 2.27]) as well as cardiac (RR 1.37 [1.00, 1.89]) and vascular disorders (RR 1.74 [1.05, 2.86] for linagliptin) emerged as adverse events associated with DPP-4 inhibitor treatment. The risk of hypoglycaemia was low with DPP-4 inhibitor treatment (RR 0.92 [0.74, 1.15] compared to placebo, RR 0.20 [0.17, 0.24] compared to sulphonylureas) in the absence of sulphonylurea or insulin co-therapy, but significantly elevated for combination therapy of sulphonylurea or insulin with sitagliptin or linagliptin (RR 1.86 [1.46, 2.37] compared to placebo). A large body of data supports the long-term safety of gliptin treatment and refutes an increased risk of infections. Further research is needed to clarify a possible link to asthenia, cardiac and vascular events. For combination therapy with insulin or insulin secretagogues, a careful choice of the agent used may limit the risk of hypoglycaemia.

Bloodstream infections in paediatric cancer patients. Prospective comparative study in 2 university hospitals.

BACKGROUND: Preventive approaches (including those related to care of long term central venous catheters, CVADs) and the incidence of bloodstream infections (BSI) in 2 German university affiliated paediatric oncology units. PATIENTS AND METHODS: Non-interventional prospective observational study using the Oncoped surveillance module. Center A included 85 patients in 31 months and Center B 84 patients in 21 months. The populations did not differ in terms of age, gender, malignancy and disease status (first illness vs. relapse). Center A used ports (46 %) and 2 different Broviac catheters (54 %), in Center B nearly all patients with a CVAD had Broviacs (96 %). 30 BSI (24 patients) were diagnosed in Centre A and 28 BSI (22 patients) in Center B. Patients with relapsed malignancy experienced more BSI (51.4 % vs. 20.9 %; p = 0.001). Incidence rates were significantly lower in Center A (3.47 vs. 7.93 BSI/1000 CVAD days; p = 0.037). Poisson regression analysis revealed a significant lower incidence density (BSI/100 inpatient days) for all BSI in Center A (RR 0.47 CI95 0.27-0.81, p = 0.006). Overall, 52 % of all pathogens detected in blood cultures in Center A were Gram-positive (57 % in Center B) and 48 % Gram-negative (43 in Center B). One ALL patient without a CVAD died due to overwhelming sepsis caused by an ESBL-producing E. cloacae isolate. CONCLUSION: Paediatric cancer treatment centers differ substantially in regard to management of CVADs and in other preventive strategies. The most important use of local surveillance data is longitudinal internal assessment in close cooperation with microbiology and hospital hygiene experts.

Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Impact of platelets and fresh frozen plasma in contrast to red cell concentrate on unstimulated and stimulated cytokine release in an in vitro model of transfusion.

Transfusion of blood may contribute to immunomodulation. Leuco-depleted standard blood products are supposed to result in less immunomodulation compared with whole blood. To determine the influence of leuco-depleted blood products on the cytokine response, red blood cell concentrates (RBC), fresh frozen plasma (FFP) and platelet concentrates (PC) were investigated in an in vitro model of blood transfusion. Leuco-depleted standard blood bank RBC, FFP and PC were mixed in vitro with AB0 compatible venous blood from healthy volunteers in ratios of 3:1, 1:1 and 1:3. Specimens were incubated in presence or absence of lipopolysaccharide, 1 mug/ml. After 24 h of incubation cytokine release of tumour necrosis factor (TNF)-alpha and interleukin-10 (IL-10) was measured in cell culture supernatants by means of enzyme-linked immunsorbent assay. Addition of RBC, FFP and PC to venous blood from healthy volunteers led to a significant and dose-dependent increase in spontaneous TNF-alpha and IL-10 release. After endotoxin stimulation, RBC, FFP and PC significantly suppressed the TNF-alpha response, while the stimulated release of IL-10 tended to increase, reaching significance only after high doses of FFP. Addition of leuco-depleted blood products changed the spontaneous and stimulated cytokine response in an in vitro model of transfusion. These data may suggest a possible contribution of transfused FFP and PC to immunomodulation after transfusion similar to RBC.

Medication adherence among patients with chronic diseases: a survey-based study in pharmacies.

BACKGROUND: Poor adherence to medication leads to worsening of the disease, increased mortality and substantial rise in health care costs. AIM: It was our aim to evaluate drug adherence and influencing factors in a cohort of non-selected adult pharmacy customers with various chronic diseases and following long-term treatment. DESIGN AND METHODS: We conducted an 8 week anonymized survey in 152 German pharmacies using the Morisky Medication Adherence Scale to measure medication adherence and a questionnaire comprising questions on multiple factors with potential impact on adherence. Depression was assessed applying the Patient Health Questionnaire-9. RESULTS: In total, 1192 patients were included showing an overall adherence rate of 59.1%. A positive association to drug adherence was found in univariate analysis for non-smoking status, retirement, less disease related complaints, positive belief in drug effects, comprehensive knowledge about the disease and high quality of care by the physician and pharmacist. Multivariate regression analysis revealed that no or minimal depression (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.7-3.0), higher patient age (>63 years) (OR 2.2, CI 1.7-2.8), high perceived importance of the medication (OR 2.0, CI 1.5-2.6), good tolerability of the medication (OR 2.0, CI 1.2-3.5) and drug effect as expected or better (OR 1.6, CI 1.1-2.3) were positively correlated with adherence. CONCLUSIONS: Suboptimal adherence to medication is common in pharmacy customers with chronic diseases. The determined factors influencing adherence may help to identify patients at risk for nonadherence and support the need of improvement in physicians' communication with patients to achieve adequate adherence rates.

Differential CXC receptor expression in colorectal carcinomas.

In this study, we aimed to assess the expression profile of chemokine receptors CXCR1-4 in inflammatory and malignant colorectal diseases and corresponding hepatic metastases of synchronous and metachronous origin to elucidate their role in colorectal cancer (CRC) progression and metastasis. Chemokine receptor expression was assessed by quantitative real-time PCR, immunohistochemistry (IHC) and Western blot analysis in resection specimens from patients with ulcerative colitis (UC, n = 25), colorectal adenomas (CRA, n = 8), different stages of CRC (n = 48) as well as colorectal liver metastases (CRLM) along with their corresponding primary colorectal tumours (n = 16). While none of the chemokine receptors were significantly upregulated or downregulated in UC or CRA tissues, CXC receptors 1, 2 and 4 demonstrated a significant increase in expression in all tumour stages of CRC specimens with CXCR4 correlating with tumour grading (P < 0.05). On the other hand, CXCR3 showed no significant upregulation in either tumour stage, but significant overexpression in CRLM. While CXCR4 demonstrated significant upregulation in both tumour entities, IHC analysis revealed that the predominate cell type expressing CXCR4 in CRC is represented by tumour cells, whereas in CRLM the majority of positive CXCR4 signals is due to hepatocytes along the tumour invasion front. In conclusion, our findings show a very differential expression pattern of the four receptors in colorectal carcinomas and their corresponding liver metastases with prominent expression profiles that indicate a potential role in the pathogenesis of CRC.

Erythropoietin messenger RNA levels in developing mice and transfer of 125I-erythropoietin by the placenta.

Erythropoietin (EP) mRNA was measured in normal and anemic mice during fetal and postnatal development. Normal fetal livers at 14 d of gestation contained a low level of EP mRNA. By day 19 of gestation, no EP mRNA was detected in normal or anemic fetal livers or normal fetal kidneys, but anemic fetal kidneys had low levels of EP mRNA. Newborn through adult stage mice responded to anemia by accumulating renal and hepatic EP mRNA. However, total liver EP mRNA was considerably less than that of the kidneys. Juvenile animals, 1-4 wk old, were hyperresponsive to anemia in that they produced more EP mRNA than adults. Moreover, nonanemic juveniles had readily measured renal EP mRNA, whereas the adult level was at the lower limit of detection. Because of the very low level of fetal EP mRNA, placental transfer of EP was evaluated. When administered to the pregnant mouse, 125I-EP was transferred in significant amounts to the fetuses. These results indicate that in mice the kidney is the main organ of EP production at all stages of postnatal development and that adult kidney may also play some role in providing EP for fetal erythropoiesis via placental transfer of maternal hormone.

Placental transport of vitamin B12 in the pregnant rat.

Placental transport of vitamin B(12) was studied in the pregnant rat in two series of experiments. In the first series animals were given cyanocobalamin-(57)Co intravenously at various stages of gestation. High specific activity tracer was used and doses of B(12) were 1-2 ng per animal. The rats were killed from 15 min to 24 hr after injection and the fetuses, placentas, and serum were assayed for radioactivity. In the second series using uninjected animals, absolute amounts of vitamin B(12) in fetuses and placentas were measured at stages of gestation from day 12 through day 20. There was a progressive increase in B(12) transferred to the fetus during gestation. Although the quantity of vitamin B(12) transported per 24 hr was proportional to fetal weight, the amount transported per gram of placenta increased tenfold from day 10 through day 19. Uptake of tracer B(12) by placenta was initially rapid; however, no radioactivity appeared in the fetus until 2 hr after injection. The actual amount of B(12) in placenta increased throughout gestation, and the placental concentration of B(12) was greater than maternal plasma and fetal tissue concentrations at all times measured. These data suggest that the ability of placenta to transport B(12) increased throughout gestation, and that the rate-limiting step in the transport process was either the passage of B(12) from the maternal to the fetal side of placenta or the transfer from placenta into fetal plasma.

Bacterial toxins affect early events of T lymphocyte activation.

The effects of pertussis toxin and cholera toxin on early events of T lymphocyte activation were examined in the T lymphocyte cell line, Jurkat. Pertussis toxin treatment of these T cells increased inositol phosphates production and led to increases in intracellular free calcium concentration. These effects were produced by the isolated B (binding) subunit of pertussis toxin, alone. Inositol phosphates production resulting from perturbation of the T cell antigen receptor-CD3 complex by MAb was not affected by pertussis toxin treatment but was markedly inhibited by cholera toxin. This effect of cholera toxin paralleled elevations in cAMP content. However, forskolin, in concentrations equipotent for cAMP production, was a weaker inhibitor of inositol phosphates production. Cholera toxin inhibition of inositol phosphates production did not result from inhibition of baseline incorporation of inositol into phosphoinositide substrates of phospholipase C. These studies underline the complexity of toxin effects on cellular systems and suggest that other approaches will be required to implicate guanine nucleotide-binding regulatory proteins in control of the early events of T lymphocyte activation. However, the data presented here provide a molecular basis for the clinical observations of lymphocytosis and the in vitro observations of lymphocyte mitogenesis after pertussis toxin stimulation.

Influence of the Preoperative Decision-Making Process on the Postoperative Outcome after Hysterectomy for Benign Uterine Pathologies.

Introduction: The aim of this study was to assess whether the preoperative decision-making process might influence treatment success in premenopausal women undergoing hysterectomy for benign uterine pathologies Materials and Methods: All premenopausal women treated with hysterectomy for benign uterine pathologies between April 2011 and June 2013 at a tertiary university center were enrolled in this prospective observational cohort study. Five parameters of the preoperative decision-making process were assessed upon their correlation with postoperative quality of life, sexual function and patients' satisfaction. These outcome measures were assessed for the pre- and postoperative (six months after surgery) status using two validated questionnaires (EQ-5D and "female sexual function index" (FSFI). Patients' satisfaction with the postoperative outcome was assessed with a self-developed questionnaire. Results: 255 of 402 (63 %) patients completed the study. A correlation between the co-variables "interval between first counseling and decision to surgery", "subjectively perceived quality of the preoperative counseling" and "certainty in the decision for the intervention" and postoperative outcomes were found. The co-variables "person mainly responsible for election of hysterectomy mode" and "discussion of decision for surgery with others" showed no influence on postoperative patients-reported outcomes. Conclusion: We found a correlation between certain parameters of the preoperative decision-making process and postoperative patient-reported sexual function, quality of life and patients' satisfaction in premenopausal women undergoing hysterectomy for benign uterine pathologies. An optimization of these factors could contribute to an improvement in treatment outcomes.