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Evaluates the potential for the secondary organic aerosol formation automotive exhaust emissions. Determination of hygroscopic potential of the aerosol; Organic analysis of aerosol formation; Functional group analysis of organic aerosol.

Background: Long-acting reversible contraceptives, including hormonal levonorgestrel-releasing intrauterine systems, are the most effective methods of reversible contraception. However, unfavorable bleeding, particularly during the first months of use, is one of the most important reasons for discontinuation or avoidance. Minimizing this as early as possible would be highly beneficial. Nonsteroidal anti-inflammatory drugs inhibiting prostaglandin synthesis are known to reduce bleeding and pain at time of menses. A levonorgestrel-releasing intrauterine system has been developed with an additional reservoir containing indomethacin, designed to be released during the initial postplacement period., Objective: This proof-of-concept study aimed to establish whether the addition of indomethacin to the currently available levonorgestrel-releasing intrauterine system (average in vivo levonorgestrel release rate of 8 μg/24 h during the first year of use) reduces the number of bleeding and spotting days during the first 90 days of use compared with the unmodified system. The dose-finding analysis included 3 doses of indomethacin-low (6.5 mg), middle (12.5 mg), and high (15.4 mg)-to determine the ideal dose of indomethacin to reduce bleeding and spotting days with minimal side-effects., Study Design: This was a multicenter, single-blinded, randomized, controlled phase II trial conducted between June 2018 and June 2019 at 6 centers in Europe. Three indomethacin dose-ranging treatment groups (low-, middle-, and high-dose indomethacin/levonorgestrel-releasing intrauterine system) were compared with the unmodified levonorgestrel-releasing intrauterine system group, with participants randomized in a 1:1:1:1 ratio. The primary outcome was the number of uterine bleeding and spotting days over a 90-day reference (treatment) period. Secondary outcomes were the number of women showing endometrial histology expected for intrauterine levonorgestrel application and the frequency of treatment-emergent adverse events. Point estimates and 2-sided 90% credible intervals were calculated for mean and median differences between treatment groups and the levonorgestrel-releasing intrauterine system without indomethacin. Point and interval estimates were determined using a Bayesian analysis., Results: A total of 174 healthy, premenopausal women, aged 18 to 45 years, were randomized, with 160 women eligible for the per-protocol analysis set. Fewer bleeding and spotting days were observed in the 90-day reference period for the 3 indomethacin/levonorgestrel-releasing intrauterine system dose groups than for the levonorgestrel-releasing intrauterine system without indomethacin group. The largest reduction in bleeding and spotting days was achieved with low-dose indomethacin/levonorgestrel-releasing intrauterine system, which demonstrated a point estimate difference of -32% (90% credible interval, -45% to -19%) compared with levonorgestrel-releasing intrauterine system without indomethacin. Differences for high- and middle-dose indomethacin/levonorgestrel-releasing intrauterine system groups relative to levonorgestrel-releasing intrauterine system without indomethacin were -19% and -16%, respectively. Overall, 97 women (58.1%) experienced a treatment-emergent adverse event considered related to the study drug, with similar incidence across all treatment groups including the unmodified levonorgestrel-releasing intrauterine system. These were all mild or moderate in intensity, with 6 leading to discontinuation. Endometrial biopsy findings were consistent with effects expected for the levonorgestrel-releasing intrauterine system., Conclusion: All 3 doses of indomethacin substantially reduced the number of bleeding and spotting days in the first 90 days after placement of the levonorgestrel-releasing intrauterine system, thus providing proof of concept. Adding indomethacin to the levonorgestrel-releasing intrauterine system can reduce the number of bleeding and spotting days in the initial 90 days postplacement, without affecting the safety profile, and potentially improving patient acceptability and satisfaction., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The secondary use of deidentified but not anonymized patient data is a promising approach for enabling precision medicine and learning health care systems. In most national jurisdictions (e.g., in Europe), this type of secondary use requires patient consent. While various ethical, legal, and technical analyses have stressed the opportunities and challenges for different types of consent over the past decade, no country has yet established a national consent standard accepted by the relevant authorities., Methods: A working group of the national Medical Informatics Initiative in Germany conducted a requirements analysis and developed a GDPR-compliant broad consent standard. The development included consensus procedures within the Medical Informatics Initiative, a documented consultation process with all relevant stakeholder groups and authorities, and the ultimate submission for approval via the national data protection authorities., Results: This paper presents the broad consent text together with a guidance document on mandatory safeguards for broad consent implementation. The mandatory safeguards comprise i) independent review of individual research projects, ii) organizational measures to protect patients from involuntary disclosure of protected information, and iii) comprehensive information for patients and public transparency. This paper further describes the key issues discussed with the relevant authorities, especially the position on additional or alternative consent approaches such as dynamic consent., Discussion: Both the resulting broad consent text and the national consensus process are relevant for similar activities internationally. A key challenge of aligning consent documents with the various stakeholders was explaining and justifying the decision to use broad consent and the decision against using alternative models such as dynamic consent. Public transparency for all secondary use projects and their results emerged as a key factor in this justification. While currently largely limited to academic medicine in Germany, the first steps for extending this broad consent approach to wider areas of application, including smaller institutions and medical practices, are currently under consideration., (Copyright © 2022. Published by Elsevier Inc.)

The academic research environment is characterized by self-developed, innovative, customized solutions, which are often free to use for third parties with open-source code and open licenses. On the other hand, they are maintained only to a very limited extent after the end of project funding. The ToolPool Gesundheitsforschung addresses the problem of finding ready to use solutions by building a registry of proven and supported tools, services, concepts and consulting offers. The goal is to provide an up-to-date selection of "relevant" solutions for a given domain that are immediately usable and that are actually used by third parties, rather than aiming at a complete list of all solutions which belong to that domain. Proof of relevance and usage must be provided, for example, by concrete application scenarios, experience reports by uninvolved third parties, references in publications or workshops held. Quality assurance is carried out for new entries by an agreed list of admission criteria, for existing entries at least once a year by a special task force. Currently, 79 solutions are represented, this number is to be significantly expanded by involving of new editors from current national funding initiatives in Germany.

Older people are a high-risk group for coronavirus disease 2019 (COVID-19) because of a range of factors, including age-related changes in anatomical pulmonary and muscle function, decreased immunity and increased inflammation. These factors partly explain why older people with COVID-19 experience more severe symptoms and higher mortality than younger adults and are more likely to require nutritional support. Furthermore, there is an association between suboptimal nutritional status and poorer recovery from COVID-19. Therefore, nutritional interventions are an important aspect of care for older people with COVID-19. All members of the multidisciplinary team, including dietitians and nurses, need to assess, treat and prevent nutritional deficiencies in older people with COVID-19. This literature review provides an overview of the evidence regarding the role of nutritional interventions in the treatment of, and recovery from, COVID-19 in older people., Competing Interests: None declared, (© 2021 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Objective: To determine whether serum human follicle-stimulating hormone (FSH) levels after single subcutaneous dosing of highly purified human menopausal gonadotropins (HP-hMG) in a liquid formulation and a powder formulation are bioequivalent., Materials and Methods: This was a randomized, two-way, crossover, single-dose, bioequivalence trial comparing Menopur liquid injected by pre-filled pen, with Menopur powder injected by conventional syringe and needle. The primary endpoints were AUC t and C max of baseline-adjusted FSH. Pituitary-suppressed, healthy women were administered single subcutaneous injections of 450 IU Menopur liquid (600 IU/0.96 mL) and 450 IU Menopur powder (by 2 subcutaneous injections of 225 IU in 1 mL) in a randomized order. The pharmacokinetic parameters of FSH and human chorionic gonadotropin (hCG) were assessed by non-compartmental methods with adjustment for endogenous pre-dose levels., Results: In total, 76 women were randomized, and 56 completed the trial. The mean FSH and hCG serum concentration-time profiles were comparable between the two HP-hMG formulations. The geometric mean ratios and 90% confidence intervals of FSH for HP-hMG liquid versus HP-hMG powder were 1.12 (1.0562 - 1.1889) for AUC t and 1.17 (1.0946 - 1.2490) for C max , showing that the two formulations were bioequivalent. The incidence and severity of adverse events were similar between the two preparations, and both preparations were well tolerated., Conclusion: The 90% CIs for the geometric mean ratios of serum FSH AUC t and C max were both within 0.8000 - 1.2500, thus the two formulations are bioequivalent.

Objective: To examine the impact of a 1-year pragmatic obesity trial on primary care providers' (PCPs) perspectives of treatment., Methods: PCPs from four intervention clinics (PCP-I) and five control clinics (PCP-C) completed pre- and postintervention surveys on weight-loss counseling, comfort discussing obesity treatments, and perceived effectiveness of interventions; questions were rated on 0 to 10 Likert scales. Only PCP-I received patient updates and education about obesity management., Results: Eighty PCPs completed preintervention surveys (pre: 71% female, 71% physicians); 82 PCPs completed postintervention surveys (post: 66% female, 70% physicians). PCPs were most comfortable discussing exercise before and after the trial (pre PCP-C: 8.22 [1.44], mean [standard deviation (SD)]; post PCP-C: 8.37 [1.24]; P = 0.8; pre/post PCP-I: 7.88 [1.51] vs. 7.80 [1.71]; P = 0.3). PCPs were initially least comfortable discussing phentermine/topiramate extended release (ER) but developed significantly more comfort after the trial, to a greater degree among PCP-I (pre/post PCP-C: 2.86 [2.66] vs. 3.73 [2.72], P < 0.001; pre/post PCP-I: 4.00 [2.57] vs. 6.17 [2.27], P < 0.001). After the trial, both PCPs rated exercise significantly less effective for weight loss, with a greater decrease in effectiveness rations among PCP-I (pre/post PCP-C: 7.73 [1.94] vs. 6.93 [2.35], P = 0.017; pre/post PCP-I: 6.27 [2.69] vs. 5.15 [2.31], P = 0.001). Both PCPs rated phentermine (pre/post PCP-C: 5.03 [2.05] vs. 5.50 [2.12], P = 0.002; pre/post PCP-I: 5.70 [1.64] vs. 6.83 [1.18], P = 0.001) and phentermine/topiramate ER (pre/post PCP-C: 3.91 [2.33] vs. 5.47 [2.54], P < 0.001; pre/post PCP-I: 5.58 [2.21] vs. 7.02 [1.47], P < 0.001) significantly more effective after the trial, though ratings were higher among PCP-I., Conclusions: PCPs initially overvalued exercise and undervalued weight-loss medications. PCPs exposed to education and experience gave higher comfort and effectiveness ratings to weight-loss medications., (© 2018 The Obesity Society.)

Tubal factor infertility (TFI) accounts for more than 30% of the cases of female infertility and mostly resides from an inflammatory process triggered by an infection. Clinical appearances largely differ, and very often infections are not recognized or remain completely asymptomatic over time. Here, we characterized the microbial pattern in females diagnosed with infectious infertility (ININF) in comparison to females with non-infectious infertility (nININF), female sex workers (FSW) and healthy controls (fertile). Females diagnosed with infectious infertility differed significantly in the seroprevalence of IgG antibodies against the C. trachomatis proteins MOMP, OMP2, CPAF and HSP60 when compared to fertile females. Microbiota analysis using 16S amplicon sequencing of cervical swabs revealed significant differences between ININF and fertile controls in the relative read count of Gardnerella (10.08% vs. 5.43%). Alpha diversity varies among groups, which are characterized by community state types including Lactobacillus-dominated communities in fertile females, an increase in diversity in all the other groups and Gardnerella-dominated communities occurring more often in ININF. While all single parameters did not allow predicting infections as the cause of infertility, including C. trachomatis IgG/IgA status together with 16S rRNA gene analysis of the ten most frequent taxa a total of 93.8% of the females were correctly classified. Further studies are needed to unravel the impact of the cervical microbiota in the pathogenesis of infectious infertility and its potential for identifying females at risk earlier in life.

Homeostasis is the process by which cells adapt to stress and prevent or repair injury. Unique programs have evolved to sense and activate these homeostatic mechanisms and as such, homeostatic sensors may be potent therapeutic targets. The hypoxic response mediated by hypoxia inducible factor (HIF) downstream of oxygen sensing by HIF prolyl 4-hydroxylases (PHDs) has been well-studied, revealing cell-type specific regulation of HIF stability, activity, and transcriptional targets. HIF's paradoxical roles in nervous system development, physiology, and pathology arise from its complex roles in hypoxic adaptation and normoxic biology. Understanding how to engage the hypoxic response so as to recapitulate the protective mechanism of ischemic preconditioning is a high priority. Indeed, small molecules that activate the hypoxic response provide broad neuroprotection in several clinically relevant injury models. Screens for PHD inhibitors have identified novel therapeutics for neuroprotection that are ready to proceed to clinical trials for ischemic stroke. Better understanding the mechanisms of how to engage hypoxic adaption without altering development or physiology may identify additional novel therapeutic targets for diverse acute and chronic neuropathologies.

Background: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies., Methods/design: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography., Discussion: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Introduction: Regional citrate anticoagulation (RCA) is used as an anticoagulant for continuous renal replacement therapy (CRRT). A systemic calcium (Ca2+) infusion is required to replace Ca2+ lost in the effluent. The shortage of intravenous Ca2+ in the United States has limited RCA use. We describe a continuous veno-venous hemofiltration (CVVH) protocol with RCA using 2.2% anticoagulant citrate dextrose formula-A (ACD-A) and a commercial dialysate containing Ca2+ 1.5 mmol/l (N × Stage) as post-filter replacement fluid (RF), without need for Ca2+ infusion., Methods: We prospectively evaluated five patients on CRRT who had at least three episodes of filter clotting within 24 h. Patients were switched to CVVH using ACD-A infused pre-blood pump and titrated to achieve a post-filter ionized calcium (iCa2+) level <0.5 mmol/l. The Ca2+ -containing dialysate was delivered post-filter as RF., Results: Steady state mean serum chemistries were: Na+: 140.8 ± 2.3 meq/l, K+: 4.2 ± 0.4 meq/l, HCO3-: 30.9 ± 3.7 meq/l, pH: 7.42 ± 0.07, CO2: 47.9 ± 8.3 mmHg, total Ca2+: 8.08 ± 1.09 mg/dL. Post-filter iCa2+ ranged 0.27-0.36 mmol/l, and patient iCa2+ ranged 0.81-1.24 mmol/l. Mean post-filter RF rate: 3086 ± 164 ml/h, mean ACD-A rate: 298 ± 21 ml/h. Mean blood flow rate: 200 ± 17 ml/min, mean filtration fraction: 39.6 ± 7.2%. Mean effluent flow rate: 38.6 ± 6.7 ml/kg/h (range 28.7-55.8). Mean filter survival was 7 h without anticoagulation, compared to 42.6 h in the ACD-A group (p<0.0001)., Conclusions: In this pilot study, CVVH using ACD-A for RCA and a Ca2+ -containing RF was safely and effectively used without a continuous Ca2+ infusion. This protocol is a promising solution for maintaining effective CRRT when intravenous calcium is in short supply.

Objectives: The association between malnutrition and poor patient outcome has been established for different medical fields. There is a general lack of data on the prevalence of malnutrition in urologic patients. An assessment of malnutrition is needed to raise awareness of this condition and to initiate nutrition therapy if needed., Methods: The nutritional state of 897 patients was assessed prospectively using the Nutritional Risk Screening 2002 (NRS) at a urologic department. Recruitment started in January 2007 and closed in July 2007. Of the 897 patients, 751 were men (84%) and 146 (16%) were women. The median age was 66 years (range 18-98). Of the 897 patients, 441 presented with benign disease and 456 with malignant disease., Results: A severe risk of malnutrition was diagnosed in 144 patients (16%; NRS score >or=3). The NRS score was 0, 1-2, and 3-5 in 45, 708, and 144 patients, respectively. Age and malignant disease were significant risk factors for malnutrition (P < .001). Also, the type of surgery was significantly associated with the risk of malnutrition (P < .001). Sex and body mass index had no significant influence. Of the patients with an NRS score of >or=3, 94% presented with >or=1 of the 3 risk factors: older age, open surgery, and/or malignant disease (P < .001)., Conclusions: In the present study, 16% of urologic patients were at a severe risk of malnutrition according to the NRS 2002. Older age, type of procedure, and malignant disease proved to be significant factors for a greater risk of malnutrition. Adequate nutritional supportive therapy should be considered in these patients to optimize their clinical outcome.

Phosphoprotein driven cellular signaling events represent most of the new molecular targets for cancer treatment. Application of reverse-phase protein microarray technology for the study of ongoing signaling activity within breast tumor specimens holds great potential for elucidating and profiling signaling activity in real-time for patient-tailored therapy. Analysis of laser capture microdissection primary human breast tumors and metastatic lesions reveals pathway specific profiles and a new way to classify cancer based on functional signaling portraits. Moreover, the data demonstrate the requirement of laser capture microdissection for analysis and reveal the metastasis-specific changes that occur within a new microenvironment. Analysis of biopsy material from clinical trials for targeted therapeutics demonstrates the feasibility and utility of comprehensive signal pathway activation profiling for molecular analysis.

While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and "in use" within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This "wiring diagram" can serve as the basis for both, selection of a therapy and patient stratification.

Breast cancer is one of the most common cancers observed in women in industrialized Western countries. The development of novel diagnostic methods and the application of modern systemic therapies have significantly optimized early detection and therapy of breast cancer. However, many patients are currently overtreated. Traditionally, tumours have been categorized on the basis of histopathological criteria. However, staining pattern and intensity of cancer cells are not sufficient to reflect the molecular events driving tumour development and progression. Therefore, new genomic, transcriptomic and proteomic techniques are applied to clinical samples aiming to identify new targets for a therapy tailored for an individual patient. After an introduction to common genomic and transcriptomic profiling technologies and their relevance for clinical use, we will focus on analytical and preanalytical applications for the identification of new therapeutic targets by protein profiling, with a special emphasis on two-dimensional gel-technologies (2D-PAGE), particularly as they apply to the study of breast cancer.

The deciphering of the human genome has elucidated our biological structural design and has generated insights into disease development and pathogenesis. At the same time, knowledge of genetic changes during disease processes has demonstrated the need to move beyond genomics towards proteomics and a systems biology approach to science. Analyzing the proteome comprises more than just a numeration of proteins. In fact, it characterizes proteins within cells in the context of their functional status and interactions in their physiological micro- and macroenvironments. As dysregulated signaling often underpins most human diseases, an overarching goal of proteomics is to profile the working state of signaling pathways, to develop 'circuit maps' of normal and diseased protein networks and identify hyperactive, defective or inoperable transduction pathways. Reverse-phase protein microarrays represent a new technology that can generate a multiplex readout of dozens of phosphorylated events simultaneously to profile the state of a signaling pathway target even after the cell is lyzed and the contents denatured.

Background: Determination of Her-2/neu overexpression in breast cancer has previously been shown to be of prognostic significance. In this study, Her-2/neu expression in breast cancer was characterised by real-time PCR (RLT-PCR) based LightCycler-HER-2/neu DNA Quantification with immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH)., Material and Methods: Fifteen specimens of invasive breast cancer - whole tissue sections as well as microdissected tumour cells - were subjected to RLT-PCR. Additionally, IHC and FISH were performed., Results: Her-2/neu overexpression was detected by FISH and by real-time PCR in the same tumours. In contrast, IHC revealed discordant results., Conclusion: Determination of Her-2/neu amplification by real-time PCR is a sensitive and specific method with some advantages over FISH. This method is simple and reliable and has the potential of categorizing those tumours with borderline Her-2/neu overexpression as determined by IHC.

Objective: The role of glycodelin in human reproduction and gynecological malignancies has been investigated in a large number of studies in recent years. Three dominant functions of this glycoprotein were identified. Glycodelin is immunosuppressive, a morphological marker of differentiation and a contraceptive. Glycodelin is a glycoprotein with a molecular weight of 28 kDa and a carbohydrate content of 17.5%. Unusual LacdiNAc structures were identified on glycodelin A, isolated from amniotic fluid. Because no kit for glycodelin quantification is commercially available, we developed all reagents and a functional ELISA., Materials and Methods: Glycodelin A was purified from amniotic fluid by chromatographic methods. The purity of the isolated protein was checked with SDS-PAGE. Polyclonal antibodies against glycodelin were generated in rabbits. Monoclonal antibodies against glycodelin were generated from immunized BALB/c mice. Positive hybridomas were cloned and cultured. Monoclonal antibodies were isolated by immunoadsorption chromatography from culture supernatants. The glycodelin ELISA was developed in two formats, namely coating with polyclonal antibodies and the use of monoclonal antibodies., Results: The factors of variance for the ELISA were 7% (intraassay variance) and 15% (inter-assay variance). The glycodelin ELISA was used to determine the glycodelin A concentration in sera of fertile women during the proliferative and secretory phases of the endometrium. The glycodelin A concentration was insignificantly elevated in the secretory phase compared to the proliferative phase. Significantly higher levels of glycodelin A were found in women using oral contraceptives compared to women who were not (p<0.001). This is probably due to progesterone, which stimulates glycodelin production. We also found significantly increased glycodelin concentrations in the fluids of malignant ovarian cysts compared to benign ovarian tumors (p<0.001). Furthermore, we tested the monoclonal and polyclonal antibodies successfully in Western blot analysis and immunoadsorption chromatography., Conclusion: We consider the described ELISA for the quantification of glycodelin as a useful tool for the determination of glycodelin in amniotic fluid, serum and cystic fluids. Its most promising application is expected in the diagnosis of ovarian cancer. The antibodies generated are applicable to multiple techniques.

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.

Background: One blood system for PLTs (INTERCEPT, Baxter Transfusion Therapies) is based on photochemical treatment (PCT) with small molecules that target cross-link nucleic acids (Helinx technology, Cerus Corp.) with amotosalen-HCl (S-59) and UVA light (320-400 nm) to inactivate pathogens and WBCs., Study Design and Methods: A two-arm in vitro study was conducted to compare pooled buffy-coat-derived PLT concentrates (PCs) treated with the INTERCEPT blood system, resuspended in PLT additive solution (PAS) III (InterSol, Baxter Transfusion Therapies), and stored for up to 7 days (test units, n = 20) with unpaired, nontreated PCs, resuspended in PAS II (T-Sol, Baxter Transfusion Therapies), and prepared at the same center in the same manner (control units, n = 18)., Results: PLT dose (x 1011/unit +/- SD) on Day 1 immediately following PCT was 3.0 +/- 0.4 for test units and 3.2 +/- 0.4 for control units. After 7 days of storage, the pH of all test units was maintained above 6.8. No marked trend was observed in the hypotonic shock response (HSR). Values among study groups were similar at the end of observation period: 68 +/- 11 percent for control unites versus 67 +/- 8 percent for test units (p > 0.05). Aggregation response to ristocetin was slightly lower in test units: at Day 7, 65 +/- 10 percent versus 76 +/- 6 percent (p < 0.05). Significantly higher (p < 0.001) glucose consumption, lactate production, and CD62P expression were observed in test units., Conclusion: Compared to nontreated PLTs, the PCT process was associated with a variety of differences of in vitro analyses. Although significant, these changes were relatively small in most cases. Characteristics correlated with survival in vivo such as HSR and swirling were comparable between both study groups, indicating that the viability of the majority of cells appears to have persisted throughout 7 days of storage. The impact of this finding, however, remains to be investigated in clinical trials performed with 7-day stored PLTs.

Highly purified fractions of isolated endometrial cells can be useful for investigating endometrial function. After a first collagenase digestion, normal human endometrial stromal and epithelial cells were separated by filtration. Glands were purified further by two collagenase digestion steps, filtration, differential sedimentations, and Ficoll gradient centrifugation. Epithelial cells were polyhedral and grew as islands in a whorl-like wavy pattern around glandular fragments. High cell culture purity was confirmed with the positive immunohistochemical reaction against cytokeratin 7,8,18,19. Isolated human glands had a similar distribution pattern of estrogen receptor (ER) and progesterone receptor (PR) as observed in vivo, suggesting that glands have a functional hormone receptor system at the time of plating. Using a specific monoclonal antibody against glycodelin A (GdA), a characteristic cyclical expression was demonstrated during the menstrual cycle. The GdA reaction was weak in the proliferative phase, increasing significantly till the late secretory phase, suggesting a similar GdA concentration in vitro as observed in vivo glands. In conclusion, this method could be a model for studying endometrial glandular cells from different menstrual phases, endometrial cell interactions, implantation mechanisms, GdA regulation mechanisms, and pharmacological or other influences on ER and PR alteration.

A series of new unsymmetrical C-substituted ethylenediamines was prepared. The substituents included branched chain alkyl, cycloalkyl, and phenyl groups. Twenty-eight new platinum compounds were prepared from these diamines and were tested for activity against leukemia L1210. The cycloalkyl substituted ethylenediamines produced especially active compounds. The phenyl-substituted analogs were generally low in activity. The activity of the complexes was compared to aqueous solubility, organic solubility, and amphipathic character. There was good indication that antitumor activity increased as aqueous solubility and hydrophilic character of the molecules increased.

Rosenberg and VanCamp first reported the bacteriostatic and antitumor properties of certain platinum coordination compounds. This pioneering work has led to the synthesis and testing of a large number of related platinum products and the clinical use of cis-dichlorodiammineplatinum (II). This drug has proven very efficacious against a wide variety of mouse tumors when employed as the sole chemotherapeutic agent and has also been combined successfully with other antitumor agents, such as cyclophosphamide and cytosine arabinsoide. Unfortunately, cis-dichlorodiammineplatinum (II) has a low therapeutic index with renal toxicity being the principal limitation of its use. This has prompted the synthesis and testing of many related platinum compounds, of which cis-dichlorobiscyclopentylamine-platinum (II) and the "platinum blues" appear most promising. Experience in the synthesis, purification, and testing of such products will be discussed together with identification of outstanding unsolved problems in this area.

Rosenberg et al discovered in the coordination complexes of platinum a new, novel type of potential antitumor agent. Cisplatin [cis-dichlorodiammine platinum (II)4 proved active against a variety of rodent tumors and acted synergistically when combined with other chemotherapeutic agents. Initial clinical tests by Hill et al in 1971, showed cisplatin to be active against malignant lymphoma, Hodgkin's disease, and certain other malignancies. Significant nephrotoxicity, nausea, and vomiting were noted. Since then, cisplatin has been tested alone and in combination chemotherapy and has proven an efficacious anticancer agent in squamous cell carcinoma of head and neck, ovarian carcinoma, disseminated testicular cancer, and others. Its therapeutic value was acknowledged when approved in 1978 by the U.S. FDA for treatment of the latter cancer. The current clinical literature indicates clearly that the full potential of this drug has not yet been realized. Hydration and diuresis have served to mitigate much of the nephrotoxicity, while significant strides toward amelioration of the nausea and vomiting have also been achieved. Literally, thousands of chemically-related congeners have been synthesized, and many have shown marked potency against rodent tumors. Very few, however, have been evaluated clinically, vis-a-vis malonato trans(-)-1,2-diaminocyclohexane platinum(II); this appears a most promising and fertile area of future investigation.