Detecting pollutant sources and pathways: High-frequency automated online monitoring in a small rural French/German transborder catchment.

Great temporal and spatial variability of inputs make comprehensive monitoring in small and middle sized rivers difficult. In this study, relevant inputs in a small river were recorded with suitable online monitoring equipment coupled in mobile water quality monitoring stations, the study area being a transborder catchment with French and German (Saarland federal state) subcatchments. In addition to a pronounced spatial variability necessitating a denser net of measuring points this catchment has also to be assessed in the light of different national regulations. To identify individual pollution sources and weigh their relative importance, relevant parameters were recorded over a representative monitoring period of several months: phosphorus (P) as total phosphorus (TP) and total reactive P phosphorus (TRP), nitrate (NO3-N), ammonium (NH4-N), total organic carbon (TOC), temperature, oxygen (O2), pH, turbidity, and electrical conductivity (EC). The recorded data were subjected to adapted interpretation together with other catchment-related factors. In order to retrieve maximum information from the online data sets the relationships among certain parameter pairs were also analysed for both storm events and low flow periods. Comparison of loads at the different monitoring sites could reliably verify the majority of nutrient inputs originating in the French subcatchment. Additional sampling of output channels from sewage treatment works (STWs) in the Saarland subcatchment revealed that inputs from several decentralised STWs do not result in significant loads, as opposed to inputs from one STW in France. Our holistic approach provides a basis for adopting cost-effective measures to reduce loads in small river catchments as well as cross-border harmonisation of environmental policies.

[Intoxicated women: A study into gender differences in substance abuse in forensic psychiatric patients]. / Vrouwen onder invloed: een studie naar genderverschillen in middelengebruik bij forensisch psychiatrische patiënten.

BACKGROUND: Substance abuse is an important risk factor for (violent) offending, but is mostly studied in male populations. More knowledge about women is needed.
AIM: To gain insight into possible gender differences in substance abuse and offending in forensic psychiatric patients.
METHOD: Files were analysed of 275 women and 275 men who have been admitted between 1984 and 2014 to one of four Dutch forensic psychiatric facilities and related to incidents of violence during treatment or recidivism after discharge (for 78 women).
RESULTS: Although substance abuse was common in women (57%), it was significantly more prevalent in men (68%). Men were more often diagnosed with substance dependency and more often committed the index-offense whilst intoxicated. Predictive accuracy for violent incidents during treatment was better for men. Both women and men with substance abuse had significantly more historical risk factors compared to those without substance abuse. A history of substance abuse was not a significant predictor for recidivism after discharge in women.
CONCLUSION: There are gender differences in substance abuse and the relationship with offending was stronger for men. These differences may have implications for substance use treatment in forensic mental health services.

Pharmacokinetics of clomipramine during pregnancy.

PURPOSE: Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pregnancy. Second, we describe Center for Epidemiologic Studies Depression scale (CES-D) scores during pregnancy. METHODS: During 13 pregnancies, every trimester and 3 months after pregnancy, the clomipramine and desmethylclomipramine concentrations were measured with LC-MSMS and the severity of depression was assessed by taking the CES-D score. All concentrations used in our calculations were in fact the ratio between actual plasma concentration (µg/l) and the actual dose (mg). We compared differences in ratios between trimesters by using the Friedman test. RESULTS: Studying 12 women and 13 pregnancies, we found no changes in mean clomipramine concentrations, a statistically significant decrease in mean desmethylclomipramine concentrations (p = 0.014) and a significant decrease in the ratio of desmethylclomipramine/clomipramine mean concentrations during pregnancy (p = 0.014) compared to the post-partum period. Sub-therapeutic concentrations of clomipramine and desmethylclomipramine were found in three patients during whole pregnancy. CONCLUSIONS: The mean concentrations of the pharmacologically active metabolite of clomipramine and desmethylclomipramine changes during pregnancy, where a decrease in mean concentrations was found during pregnancy. In case of recurrent disease, we recommend to control clomipramine and its metabolite concentrations, while both are active.

[Clinical decision making with regard to the granting of escorted leave for forensic patients detained by court order in a Dutch psychiatric clinic. Role of gender, disorder and the type of offence in the procedure]. / Behandelduur tot eerste toekenning tbs-verlof in een Nederlandse forensische psychiatrische kliniek; dossieronderzoek naar invloed van patiëntkenmerken en delict.

BACKGROUND: An increase in the length of time until the first escorted leave is granted to a patient detained by court order (tbs) results in a longer period of treatment. Physicians involved in the treatment and clinic managers are striving to reduce, in a responsible manner, the length of the period of treatment preceding the patient's first escorted leave.
AIM: Forensic Psychiatric Clinic (fpk) 'De Woenselse Poort' aims to find out to what extent gender, pathology and the type of offence committed by the detainee influence the length of time that elapses before the patient's first leave is granted. METHOD: We conducted a retrospective study based on patients' records. RESULTS: Although men use physical aggression more often than women, we found that gender, pathology and the type of offence had no influence on the length of the treatment period that preceded the granting of the patient's first escorted leave. CONCLUSION: Partly on the basis of risk management scales, clinicians judge whether the patient has adopted a more positive or a more negative attitude to risk factors relating to his or her offence. If the risk factors have become more positive, one would expect the application for leave to be made earlier. Surprisingly, this was not the case. In order to speed up the decision-making process regarding the application for leave, a clinical method for evaluating risk related treatment needs to be developed in which offence related risk factors are identified and the patient's positive or negative attitude to these risks are measured and monitored. At each treatment evaluation practitioners should be required to produce arguments that determine whether or not the patient is to be granted permission to go on leave at a particular moment.

Concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during pregnancy.

WHAT IS KNOWN AND OBJECTIVE: Depression during pregnancy is common and includes risks for mother and child. Pharmacokinetics of venlafaxine may be changed during pregnancy. This study aimed to describe changes in metabolic ratios and concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during and after pregnancy. METHODS: To study this, we used data from our study of compliance to Antidepressants During Pregnancy (the ADAP study) to investigate the course of venlafaxine and O-desmethylvenlafaxine concentrations during pregnancy and in the period post-partum. RESULTS AND DISCUSSION: We found that the venlafaxine concentration significantly changed during pregnancy when compared to the post-partum period (P = 0·028). The median concentration of venlafaxine in the first trimester was 98·9% (54·2-292·0%), the second 100·0% (46·5-264·0%) and the third trimester 87·0% (61·5-217·2%). We did not found differences in O-desmethylvenlafaxine concentrations in the different trimesters of pregnancy compared with the post-partum period, P = 0·565. Also the ratio of O-desmethylvenlafaxine/venlafaxine concentrations increased significantly from 76·9% (range 32·8-142·0%) in the first trimester to 196·7% (range 83·3-427·6%) in the third trimester compared with the post-partum period, P = 0·004. Further, three of seven patients had concentrations below the therapeutic reference range (100-400 µg/L) in any period of pregnancy, whereas no one had subtherapeutic concentrations in the post-partum period. WHAT IS NEW AND CONCLUSION: Venlafaxine concentrations decreases during pregnancy, and the ratio of the concentrations of O-desmethylvenlafaxine/venlafaxine increases during pregnancy. Pregnant women using venlafaxine are at risk for subtherapeutic concentrations, therefore routine monitoring of concentrations venlafaxine and O-desmethylvenlafaxine is recommendable during pregnancy.

[Treatment evaluation and clinical decision making using HKT-30-ROM]. / Behandelevaluatie en klinische besluitvorming met HKT-30-ROM.

BACKGROUND: By means of repeated, well-supported measurements of clinical dynamic indicators from the Historical, Clinical and Future - 30 (HKT-30) it is possible to monitor behavioural changes on the basis of risks and needs. The addition of extra score parameters allows us to distinguish client-specific risks and needs. In treatment evaluation it is important to visualise changes in these indicators of treatment evaluation because they are the key to the clinical decision-making process that determines further treatment and rehabilitation. AIM: To investigate whether HKT-30 indicators can be used to measure and visualise behavioral changes for the purpose of treatment evaluation. METHOD: A case study is used to illustrate how clinicians at the Forensic Psychiatric Clinic (FPK), De Woenselse Poort, ascertain risks, needs and changes and clarify these factors for the purpose of treatment evaluation and clinical decision-making. RESULTS: Routine treatment evaluation aided by visualised clinical HKT-30 indicators give the treatment team and the client a clearer picture of the behavioral changes for which the forensic treatment was prescribed. This evaluation provides significant starting-points for clinical decision making. CONCLUSION: Routine treatment evaluation along with a suitably adjusted HKT-30 make behavioural changes visible, render clinical decisions more transparent and provide valuable starting-points for a dialogue with the client about his treatment.

[Violent women: a multicentre study of the characteristics of female forensic psychiatric patients]. / Gewelddadige vrouwen: een multi-centeronderzoek naar kenmerken van vrouwelijke forensisch psychiatrische patiënten.

BACKGROUND: Violence perpetrated by women has attracted more and more attention in the past few years. However, there is lack of background information about women admitted to forensic psychiatric hospitals and about risk factors for recidivism. AIM: To conduct a multicenter study which will give more insight into female psychiatric patients and which will probably have implications for psychodiagnostics, risk assessment and treatment in (forensic) psychiatric settings. METHOD: We coded the files of 297 women who, between 1984 and 2013, had been admitted to one of four Dutch forensic psychiatric facilities by reason of violent delinquent behaviour. We used an extensive coding list and several risk assessment tools including the recently developed Female Additional Manual (fam) for women. RESULTS: The general picture that emerged was one of severely traumatised women with complex pathology and a high level of comorbidity. Many of the women had experienced previous treatment failures and had caused many incidents during treatment. CONCLUSION: Female forensic psychiatric patients are a complex group that deserves more specific attention. Attention for traumas from the past, intensive supervision in relationships and training for staff in dealing with, for instance, manipulative behaviour are the most important implications from this study.

In utero exposure to antidepressants and the use of drugs for pulmonary diseases in children.

PURPOSE: The use of antidepressants during pregnancy is common. Some studies suggest an association between in utero exposure to antidepressants and the occurrence of pulmonary diseases like asthma later in life. Serotonin reuptake inhibitors (SSRIs) as well tricyclic antidepressants (TCAs) are thought to be involved in the development of the respiratory rhythm generator (RRG) and the maturation of the formation of surfactant. In this study the use of drugs for pulmonary diseases in children who were exposed to antidepressants in utero were compared with non-exposed children. METHODS: The pharmacy prescription database IADB.nl was used for a cohort study in which the use of drugs for pulmonary disease in children after in utero exposure to antidepressants (TCAs, SSRIs) was compared with children with no antidepressant exposure in utero. Drugs for pulmonary diseases were applied as a proxy for disturbed development of the respiratory tract. RESULTS: A small though significant increase in the incidence risk ratio (IRR) of the use of drugs for pulmonary disease was found after any-time in utero exposure to SSRIs, adjusted for maternal use of antibiotics, of 1.17 (95 % CI 1.16-1.18). An increase was also seen when we looked specifically for the use of SSRIs in at least the first trimester (IRR = 1.18, 95 % CI 1.17-1.20). An increased IRR in the use of drugs for pulmonary disease was also seen when children were exposed to TCAs, but this was not statistically significant. However, in both groups our sample size was rather small. The effect size is modest and may also be confounded by maternal smoking. CONCLUSIONS: In utero exposure to SSRIs leads to a statistically significant increase in the use of drugs for pulmonary diseases, especially when exposure occurred during the first trimester of pregnancy. The increase in the use of drugs for pulmonary disease may also be related to other factors. Therefore, further study is recommended.

Influence of a 12-month supervised, intensive resistance, aerobic and impact exercise intervention on muscle strength in prostate cancer patients undergoing anti-hormone therapy: Study protocol for the randomized, controlled Burgdorf study.

INTRODUCTION: Reduced testosterone levels due to androgen deprivation therapy (ADT) in prostate cancer patients cause common side effects, such as reduced muscle strength and bone density, increased fat mass, sexual dysfunction and fatigue. Short-term exercise during ADT has proven to be safe and effective in exhibiting a positive impact on body composition, sexual dysfunction and fatigue. However, there are only three randomized controlled trials that investigate one-year supervised impact exercise interventions, none of which examined follow-up effects after the intervention. Therefore, this study will conduct a one-year impact exercise intervention and assess follow-up effects up to one year later. MATERIAL AND METHODS: The aim of the randomized, controlled Burgdorf study is to assess the effects of a supervised 12-month intensive multimodal exercise intervention in comparison to a moderate aerobic exercise intervention, on muscle strength in prostate cancer patients receiving ADT. Additionally, quality of life, fatigue, body composition, erectile dysfunction, bone pain, physical activity level, endurance capacity, body-mass-index, waist and hip circumference and prostate-specific antigen- and testosterone levels will be assessed up to one year later. DISCUSSION: The Burgdorf study is the first study to conduct two different one-year supervised exercise interventions, and follow-up with patients for up to one year after the intervention. Results could provide important insights into the long-term effects of interventions on those parameters negatively affected by ADT, which could specify or newly establish care structures. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00009975. Registered 2016-02-09, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009975.

Fifteen years' experience with methylphenidate for attention-deficit disorder during pregnancy: Effects on birth weight, Apgar score and congenital malformation rates.

BACKGROUND: Methylphenidate (MPD) is increasingly prescribed to fertile women with Attention-Deficit Disorder (AD(H)D), with or without hyperactivity, despite advice for discontinuation during pregnancy. Few studies report on results concerning safety after methylphenidate exposure during pregnancy for the offspring. AIM: Safety for the offspring of exposure to MPD during pregnancy. METHODS: This is an observational retrospective cohort study in a population of pregnant women and their offspring, treated with MPD for ADHD in the Psychiatry-Gynaecology-Pediatrics outpatient clinic between 1 January 2005 and 1 June 2020 at Isala hospital. The primary endpoints were birth weight and Apgar score in offspring exposed to MPD during pregnancy, compared to offspring unexposed to MPD. Birth weight was analysed using linear mixed model analysis. Apgar score and (secondary endpoint) neonatal malformations, at 20 week ultrasound, were analysed using basic univariate statistical analysis. RESULTS: MPD continuation, compared to discontinuation, was associated with higher neonatal birth weight (p = 0.049), but lost statistical significance after incorporating covariates (p = 0.079). There were no significant differences in Apgar scores and congenital malformations between neonates exposed and unexposed to MPD. CONCLUSIONS: MPD does not seem to affect birth weight, Apgar score and the frequency of neonatal malformations at the 20 week ultrasound.

Influence of geochemical parameters on the sorption and desorption behaviour of europium and gadolinium onto kaolinite.

In this study we investigated the sorption and desorption behaviour of europium and gadolinium (homologues of the actinides americium and curium) onto the clay mineral kaolinite KGa-1b. In the model system metal/kaolinite, sorption isotherms and pH-edges were determined in different batch experiments. Calcium and magnesium as competing cations were used to simulate the influence of water hardness on the sorption and desorption processes. After centrifugation, the free metal ions in the supernatant solution were analysed by ICP-MS. With increasing lanthanide concentration, especially the relative desorption of these metals from kaolinite rises significantly before the cation exchange capacity (CEC) of 0.94 meq per 100 g is reached. This indicates that low lanthanide concentrations will result in a relatively lower metal migration due to sorption reactions at higher active sites in comparison with higher lanthanide concentrations. The K(d)-values and sorption isotherms of Eu(iii) and Gd(iii) were determined at pH 5.0 (+/-0.02) and analysed with Freundlich and Langmuir sorption models. The experimental data can best be fitted by Langmuir sorption isotherm. The pH-value has only a minor influence on the sorption onto kaolinite. Only at low pH-values (

The effect of naked neck gene and ambient temperature and their interaction on reproductive traits of heavy broiler dams.

High ambient temperature is a major factor for diminishing reproductive performance of broiler parent stocks. Homozygous naked neck (NaNa) broilers, which possess a higher adaptation to heat due to a reduction of feather coverage, exhibited higher growth rates and meat yield. This study was conducted to investigate the influence of genotype x temperature interactions on the reproduction traits of heavy broiler dams caused by different feathering genotypes induced by naked neck gene (Na). In an additional experiment, the effect of Na gene on embryonic activity using oxygen uptake was examined. Normal-feathered (nana) and NaNa hens were maintained in separate cages under high (30 degrees C) and moderate (19 degrees C) temperatures, with RH of 55% from the 18th to 72nd week of age. Egg production, fertility, hatchability, and the time of embryonic mortality were recorded. In comparison with the NaNa genotype, the nana hens showed clear performance depressions under thermal stress with respect to egg production (63%), fertility (20%), hatchability, and number of chicks (72%). Under temperate ambient temperature, there were no differences in laying performance and fertility between both genotypes, with the exception of hatchability due to an increase in embryonic mortality as a result of the Na gene and consequently in the complex trait number of chicks. The early embryonic mortality of eggs laid by nana hens exposed to heat stress is clearly higher than of eggs by nana hens kept under temperate ambient temperature. In contrast, there were no significant differences in early embryonic mortality of eggs of NaNa birds kept under high and temperate environmental temperatures, demonstrating that heat stress leads to reduced early embryonic livability. Embryonic mortality in the late developing stage is significantly increased, and the homozygous genotype is much more affected than the heterozygous embryo. The possible reason for the Na gene-induced embryonic mortality is still not clear. In this investigation, it is shown that the phenomenon cannot be explained by the oxygen consumption.

The effect of frizzle gene and dwarf gene on reproductive performance of broiler breeder dams under high and normal ambient temperatures.

In 3 experimental runs, the influence of genotype × temperature interactions on the reproductive traits (sexual maturity, egg production, fertility, hatchability, and chick production) of hens of a broiler breeder dam line carrying major genes for dwarfism (dw-) and frizzle (F) was investigated. In experiments 1 and 2, the hens were caged individually under hot (30°C) and temperate (19°C) temperatures, from wk 18 to 72 of age, whereas in experiment 3, hens were kept under moderate temperature (24°C). Hens in experiment 1 were heterozygous for the frizzle gene, and those in experiments 2 and 3 were homozygous, both with and without the dwarf gene. Hens without the above-mentioned major genes (ffDw-) served as control lines. In experiment 1, the frizzle gene (Ff) had no significant effect on sexual maturity, egg production, fertility, hatchability, and chick number under the 2 environmental conditions. In experiment 2, there was a significant interaction between feathering genotype (FF) and environmental temperature for all traits except sexual maturity. Under heat stress, there was a distinct reduction in all reproductive traits except sexual maturity for normally feathered hens compared with frizzle-feathered hens, whereas under temperate conditions, egg production and number of chicks of the FF genotype were reduced and sexual maturity was delayed. In experiments 1 and 2, the dw- gene showed a depressive effect on the growth of hens. In experiment 1, the interaction between dwarf genotype and environmental temperature for egg production was significant. Under temperate conditions, the egg production of dwarf hens was inferior to that of normally sized birds, whereas under hot temperatures, the egg production of the 2 body sizes did not differ. In experiment 2, for sexual maturity, egg production and fertility locus × locus interactions could be determined. The genotype combining the 2 major genes (FFdw-) proved to be inferior to the normally feathered dwarf type (ffdw-) for laying performance but superior in fertility. Under the conditions in experiment 3, the egg production of dwarf birds was significant reduced.

eHealth vision towards cooperative patient care--domain fields and architectural challenges of regional health care networks.

Numerous eHealth projects and efforts to establish inter-organizational communication and to build up regional health care networks could be observed in the last ten years. Nevertheless the success of such efforts is profoundly different. The aim of this paper is to introduce the lately started regional initiative eHealth.Braunschweig compounding of the major health care players (hospitals, physician offices, nursing services and nursing homes) in the region of Braunschweig, participants from research institutions and industry. We propose in this paper the main goals of the regional initiative eHealth.Braunschweig, its constitution and major approaches. Based on respective literature and our former projects as well as experiences in this field we discuss our vision of a patient-oriented cooperative health care by depicting regional distinctions, identifying the major domain fields in this context and discussing the architectural challenges for the regional health care network eHealth.Braunschweig. In our view this work can be considered as a systematical approach to the establishment of regional health care networks with lasting and sustainable effects on patient-centered health care in a region.

Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence.

Staphylococcus aureus Clp ATPases (molecular chaperones) alter normal physiological functions including an aconitase-mediated effect on post-stationary growth, acetate catabolism, and entry into death phase (Chatterjee et al., J. Bacteriol. 2005, 187, 4488-4496). In the present study, the global function of ClpC in physiology, metabolism, and late-stationary phase survival was examined using DNA microarrays and 2-D PAGE followed by MALDI-TOF MS. The results suggest that ClpC is involved in regulating the expression of genes and/or proteins of gluconeogenesis, the pentose-phosphate pathway, pyruvate metabolism, the electron transport chain, nucleotide metabolism, oxidative stress, metal ion homeostasis, stringent response, and programmed cell death. Thus, one major function of ClpC is balancing late growth phase carbon metabolism. Furthermore, these changes in carbon metabolism result in alterations of the intracellular concentration of free NADH, the amount of cell-associated iron, and fatty acid metabolism. This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late-stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections.

[Antidepressants during pregnancy and lactation]. / Antidepressiva tijdens zwangerschap en borstvoeding.

BACKGROUND: It is difficult to find well-grounded advice about the pharmacotherapeutic treatment of anxiety and depression before, during and after pregnancy. Furthermore, in the literature pharmacotherapeutic advice relating to the various periods (pre-conception, pregnancy and lactation) is often contradictory. AIM: By reviewing the literature, to arrive at a recommendation for the pharmacotherapeutic treatment of depression during and after pregnancy and to compare and weigh up the various risks involved in treatment. METHOD: A literature search in PubMed and Embase with search terms 'antidepress*', 'anxiol*', 'pregnan*', 'depressi*', 'anxiet*', 'guideline', 'lactation', 'breastfeeding' and 'milk'. The National Guideline Clearinghouse database was used to find guidelines. results The literature reveals that the medical treatment of a depression during pregnancy and lactation is not without risks. However, there are also risks involved in not treating depression during these periods. These risks cannot be assessed at group-level but have to be weighed up for each individual separately. The patient needs to be informed about the risks she runs in connection with a particular treatment so that a well-considered decision can be made about whether to treat or not treat depression with antidepressants during pregnancy. CONCLUSION: If the decision is made to treat depression during pregnancy and in the lactation period, it is advisable to choose an antidepressant from the safest category; in most countries this means opting for tricyclic antidepressants.

Real-time monitoring of water quality to identify pollution pathways in small and middle scale rivers.

The quality standards for surface waters increase steadily bearing new challenges for water policy. Precise knowledge of the sources and transport pathway of various impacts in a catchment area is of particular importance for any management activities. Online measurements with high temporal resolution are particularly suited for this purpose especially in small and middle scale catchments. In this paper we present an approach applying mobile measuring stations in which commercial available sensors and wet chemical analysers are combined in a new set to enable real-time monitoring of various parameters. The resulting data and the interpretation of their relationships allow the identification of diverse pollution situations in a river. In this paper some examples of impacts from diffuse and point sources are given to illustrate the high information density obtained through the use of this system.

Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection.

BACKGROUND: Elevations of plasma vascular endothelial growth factor (VEGF) have been noted early after colorectal resection. The duration of this increase is unknown. Because VEGF is a potent promoter of angiogenesis, which is critical to tumor growth, a sustained increase in blood VEGF levels after surgery may stimulate the growth of residual metastases early after surgery. This preliminary study aimed to determine VEGF levels during the first month after colorectal resection. METHODS: Patients from three prospective studies that had late postoperative blood samples available comprised the study population. Demographic, perioperative, pathologic, and complication data were collected. Plasma samples were obtained preoperatively for all patients: on postoperative day (POD) 1 for most patients and at varying time points thereafter during the first month after surgery and beyond. Levels of VEGF were determined via enzyme-linked immunoassay (ELISA) and compared using Wilcoxon's matched pairs test. Because the numbers of specimens beyond POD 5 were limited, samples from 7-day time blocks were bundled and averaged to permit statistical analysis. RESULTS: A total of 49 patients with cancer and 30 patients with benign indications, all of whom underwent minimally invasive colorectal resection, were assessed separately. With regard to the patients with cancer, the median preoperative plasma value was 150 pg/ml, and the peak postoperative median value for the POD 14 to 20 time block was 611.1 pg/ml. Furthermore, compared with the preoperative results, significant VEGF elevations were noted on POD 3 as well as during week 2 (POD 7-13), week 3 (POD 14-20), and week 4 (POD 21-27) (p < 0.05 for each). With regard to the benign patients, the median preoperative VEGF level was 112 pg/ml, and the peak postoperative value, 286 pg/ml, was noted during postoperative week 2. Significant elevations were noted on POD 3, and for weeks 2 and 3 as well as for POD 28 and later. Between 63% and 89% of the patients at each time point beyond POD 5 had elevated VEGF levels. CONCLUSION: This preliminary study demonstrates that after minimally invasive colorectal resection for cancer, median VEGF levels are significantly elevated on POD 3 and remain increased for as long as 4 weeks. Significant elevations in a similar pattern also were noted for the benign patients. However, the baseline and postoperative median values were lower. The clinical impact from increased blood levels of VEGF is uncertain. It is possible that the growth of residual tumor deposits may be stimulated early after surgery. These results warrant a larger study as well as endothelial cell in vitro assays to determine whether postoperative plasma stimulates proliferation and invasion.

Alcohol: A Pharmaceutical and Pharmacological Point of View During Lactation.

BackgroundA safe amount of alcohol that can be ingested by suckling infants is not known. As a result, alcohol consumption by lactating mothers during this crucial time can potentially harm infants. ObjectiveThis article provides an overview of alcohol pharmacokinetics and pharmacodynamics in breast milk. Methods/DiscussionThis paper reviews literature on alcohol exposure as it relates to suckling infants. Intended and unintended alcohol exposure through breast milk may occur by skin contact, inhalation and by use of alcohol co-formulated drugs. A method for calculating the time to alcohol elimination from breast milk is also discussed. ConclusionAs there is no evidence on a safe amount of alcohol in breast milk, alcohol exposure throughout lactation should be avoided, to ensure the welfare of suckling infants.

Pro-inflammatory cytokines after different kinds of cardio-thoracic surgical procedures: is what we see what we know?

OBJECTIVE: Due to the combination of local trauma, extracorporeal circulation (ECC), and pulmonary and myocardial reperfusion, cardiac surgery leads to substantial changes in the immune system and possibly to post-operative complications. Procedures without ECC, however, have failed to demonstrate clear advantages. We hypothesized that ECC is far less important in this context than the reperfusion/reventilation of the lung parenchyma and the surgical trauma. We therefore conducted a prospective observational study to compare immune reactions after cardiac operations with those after thoracic surgery. METHODS: Serum levels of pro-inflammatory interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha as well as C-reactive protein (CRP), lipoprotein-binding protein (LBP) and procalcitonin (PCT) were measured pre-operatively (d0), at the end of the operation (dx), 6h after the operation (dx+), on the 1st (d1), 3rd (d3), and 5th (d5) post-operative days in 108 patients (pts) undergoing elective coronary artery bypass grafting (CAB) with ECC (n=42, CPB CAB), off-pump coronary artery bypass surgery (n=24, OP CAB) without ECC or thoracic surgery (n=42, TS). RESULTS: After cardiac surgery (CS), IL-6 and IL-8 increased and reached a maximum on dx+. IL-6 returned to baseline values at d3, whereas IL-8 remained elevated until d5. No difference was found between OP CAB and CPB CAB patients. In the TS patients, IL-6 increased later (dx+) and absolute levels were lower than in the CS patients. No increase in IL-8 was noted in the TS patients. Due to the high variation in the results obtained in all three groups, there was no significant change in TNF-alpha. A comparison of TS, OP CAB, and CPB CAB revealed that the CS patients had higher levels on d0, dx, d3, and d5. Serum levels of CRP, LBP, and IL-2R increased from dx+ to d5 in all groups and reached maximum values on d3. Whereas we found no difference in CRP and IL-2R between the groups, LBP levels were significantly higher from dx+ to d3 after OP CAB. PCT was elevated from dx+ to d3 in all pts. Similar levels were noted for the TS and OP CAB patients. The CPB CAB patients showed the highest levels. CONCLUSIONS: Surgical trauma and reperfusion injury appear to represent the predominant factors resulting in immunologic changes after cardiac surgery. Cardiopulmonary bypass (CPB) may be less important for immune response and acute-phase reactions than previously suspected. In addition, our data indicate a relationship between IL-6 synthesis and the degree of surgical trauma. IL-8 appears to be elevated only after cardiac surgery whereas PCT liberation depended on the use of ECC.