Autologous blood salvage in the era of patient blood management.

Almost 150 years after the first autologous blood transfusion was reported, intraoperative blood salvage has become an important method of blood conservation. The primary goal of autologous transfusion is to reduce or avoid allogeneic red blood cell transfusion and the associated risks and costs. Autologous salvaged blood does not result in immunological challenge and its consequences, provides a higher quality red blood cell that has not been subjected to the adverse effects of blood storage, and can be more cost-effective than allogeneic blood when used for carefully selected surgical patients. Cardiac, orthopaedic and vascular surgery procedures with large anticipated blood loss can clearly benefit from the use of cell salvage. There are safety concerns in cases with gross bacterial contamination. There are theoretical safety concerns in obstetrical and cancer surgery; however, careful cell washing as well as leucoreduction filters makes for a safer autologous transfusion in these circumstances. Further studies are needed to determine whether oncologic outcomes are impacted by transfusing salvaged blood during cancer surgery. In this new era of patient blood management, where multimodal methods of reducing dependence on allogeneic blood are becoming commonplace, autologous blood salvage remains a valuable tool for perioperative blood conservation. Future studies will be needed to best determine how and when cell salvage should be utilized along with newer blood conservation measures.

A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer.

BACKGROUND: This phase II study estimated the difference in objective response rate (ORR) among patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) receiving paclitaxel-carboplatin (CP) plus motesanib or bevacizumab. PATIENTS AND METHODS: Chemotherapy-naive patients (N = 186) were randomized 1:1:1 to receive CP plus motesanib 125 mg once daily (qd) (arm A), motesanib 75 mg twice daily (b.i.d.) 5 days on/2 days off (arm B), or bevacizumab 15 mg/kg every 3 weeks (q3w) (arm C). The primary end point was ORR (per RECIST). Other end points included progression-free survival (PFS), overall survival (OS), motesanib pharmacokinetics, and adverse events (AEs). RESULTS: ORRs in the three arms were as follows: arm A, 30% (95% confidence interval 18% to 43%); arm B, 23% (13% to 36%); and arm C, 37% (25% to 50%). Median PFS in arm A was 7.7 months, arm B 5.8 months, and arm C 8.3 months; median OS for arm A was 14.0 months, arm B 12.8 months, and arm C 14.0 months. Incidence of AEs was greater in arms A and B than in arm C. More grade 5 AEs not attributable to disease progression occurred in arm B (n = 10) than in arms A (n = 4) and C (n = 4). Motesanib plasma C(max) and C(min) values were consistent with its pharmacokinetic properties observed in previous studies. CONCLUSIONS: The efficacy of 125 mg qd motesanib or bevacizumab plus CP was estimated to be comparable. Toxicity was higher but manageable in both motesanib arms. Efficacy and tolerability of motesanib 125 mg qd plus CP in advanced nonsquamous NSCLC are being further investigated in a phase III study.

Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1.

Recent developments in the field of oncolytic or tumor-selective viruses have meant that the clinical applications of these agents are now being considered in more detail. Like most cancer therapies it is likely that they will be used primarily in combination with other therapeutics. Although several reports have shown that oncolytic viruses can synergize with chemotherapies within an infected cancer cell, it would be particularly important to determine whether factors released from infected cells could enhance the action of chemotherapies at a distance. Here, we demonstrate in vitro synergy between oncolytic vaccinia and taxanes. However, we also show, for the first time, that this synergy is at least partly due to the release of factors from the infected cells that are capable of sensitizing surrounding cells to chemotherapy. Several cellular factors were identified as being mediators of this bystander effect, including type I interferon released soon after infection and high-mobility group protein B1 (HMGB1) released after cell death. This represents the first description of these mechanisms for beneficial interactions between viral and traditional tumor therapies. These data may provide a direct basis for the design of clinical trials with agents currently in the clinic, as well as providing insight into the development of next generation viral vectors.

Tunneling and coupled motion in the Escherichia coli dihydrofolate reductase catalysis.

H-transfer was studied in the complex kinetic cascade of dihydrofolate reductase. Intrinsic kinetic isotope effects, their temperature dependence, and other temperature-dependent parameters indicated H-tunneling, but no 1 degrees to 2 degrees coupled motion. The data also suggested environmentally coupled tunneling and commitment to catalysis on pre-steady-state isotope effects.

Synthesis and utility of 14C-labeled nicotinamide cofactors.

A new method for the synthesis of the reduced form of beta-nicotinamide [U-14C]adenine dinucleotide 2(')-phosphate([Ad-14C]NADPH) is presented. The present synthesis results in a radioactive material with a specific activity that is greater than 220 mCi/mmol. This method could easily be adapted for syntheses of 14C-labeled NADH, NADP(+), or any nicotinamide cofactors with radiolabels in other positions. Since these cofactors are so ubiquitous, the use and applications of such labeled material has broad implications. The utility of the labeled cofactor for determination of substrates for nicotinamide-dependent enzymes in the nano- to femtomole scale, in alternative enzymatic assays, and in kinetic isotope effect studies is discussed.

Purification, analysis, and preservation of reduced nicotinamide adenine dinucleotide 2'-phosphate.

Nicotinamide-containing cofactors are ubiquitous in biological systems. Consequently, numerous assays have been developed to study such systems that involve a variety of derivatives and isotopically labeled forms of these cofactors. Often the nicotinamide ring is labeled at the C-4 position which is directly involved in the hydride transfer chemistry catalyzed by nicotinamide-dependent enzymes. A label remote from the reactive center is often also required to follow the course of a reaction or the location of the cofactor. Since the necessary labeling pattern can be as unique as the designed experiment, these cofactors need to be synthesized, analyzed, and, most preferably, preserved. The micro-scale preservation of reduced nicotinamides has long been a challenge due to the inherent lability of the reduced cofactors. Furthermore, it has been found that the reduced 2'-phosphorylated cofactor is even less stable (i.e., reduced nicotinamide adenine dinucleotide phosphate (NADPH) is more labile than reduced nicotinamide adenine dinucleotide). Presented here are methods that were established to purify nicotinamide cofactors via reverse-phase high-performance liquid chromatography (HPLC) and, most importantly, to stabilize NADPH under optimal conditions for long-term storage. Additionally, an analytical HPLC method which achieves 7-min resolution between oxidized and reduced cofactors was developed. This method also results in over 4-min resolution of these nicotinamide cofactors from various derivatives of folic acid. This analysis affords a new analytical assay for the dihydrofolate reductase-catalyzed reaction and several dehydrogenases involved in folic acid metabolism.

Kynurenine aminotransferase I activity in human placenta.

The aim of the study was to detect and characterize placental kynurenine aminotransferase I (KAT I) activity in physiological pregnancy at term. Placental KAT I was inhibited by l -glutamine, l -tryptophan, and l -phenylalanine and reached optimum activity at pH 9.8. When pyruvate was used as a co-factor, the KAT I activity was significantly higher than the activity of this enzyme in the presence of 2-oxoglutarate. In the light of our findings placental KAT I seems to have biochemical characteristics of KAT I detected in human brain.

[Birth weight and state of dentition in children with transitional dentition with regard to oral hygiene]. / Masa urodzeniowa a stan twardych tkanek zebów u dzieci z uzebieniem mieszanym z uwzglednieniem higieny jamy ustnej.

The aim of the present study was to determine the dependency between the state of dentition and the birth weight of the pupils of the third grade of primary schools in Lublin. The subjects of the examination were 150 aged 9 year and 8 months +/- 3.9 months (76 girls and 74 boys). Clinical and questionnaire tests and a statistical analysis were carried out. The obtained results and literature review seem to allow for the following conclusions: there is a relationship between the sum of dmfs and DMFs indexes and the advancement of the carious process and OHI--S--with increment of birth weight and decrement of OHI--S index the sum of dmfs and DMFs indexes decreased; there was no correlation between disturbances of teeth mineralization and the birth weight.

[Clinical features of missed abortion]. / Objawy poronienia zatrzymanego.

RATIONALE: There is no general agreement concerning the definition of missed abortion which remains one of the most commonly encountered pregnancy complication of an extremely variable clinical picture. AIM OF THIS STUDY: The analysis of the clinical symptoms of missed abortion. SETTING: Academic Medical Center. MATERIALS AND METHODS: Consecutive 50 women with non-viable pregnancy from 7 to 22 weeks, diagnosed by clinical examination, ultrasonography and serum beta-HCG evaluation were studied. RESULTS: In 92% of the missed abortion cases a vaginal spotting was observed before the diagnosis was established. The average period of the estimated retention of the products of conception was 2.8 weeks. In only one patients this period exceeded 8 weeks. The reverse correlation was established between the gravidity of a patient and the period of asymptomatic retention of the non-viable conception products in uterus. The obtained results confirm that the onset of vaginal bleeding does not reflect the moment of embryonal/fetal death.

[Laminin levels in patients with ectopic pregnancy]. / Zachowanie sie lamininy w surowicy krwi u pacjentek z objawami ciazy pozamacicznej.

Serum laminin (sL--by means of ELISA method) was evaluated in 17 patients with tubal pregnancy (TP) and 25 healthy control subjects. In patients with ruptured TP sL was significantly elevated as compared to both the controls and the patients with unruptured TP (p < 0.001). The obtained results suggest the usefulness of sL measurements in clinical management of patients with symptoms of ectopic pregnancy.

[The antioxidant-prooxidant balance in pregnancy complicated by spontaneous abortion]. / Ocena stresu oksydacyjnego na poziomie ogólnoustrojowym u pacjentek z ciaza powiklana poronieniem.

The purpose of this study was to characterize prooxidant-antioxidant balance in patients with different clinical types of spontaneous abortion. Sixty previously untreated, pregnant women aged 16-38 years were included into this study. The gestational age ranged from 8 to 12 weeks. Patients were divided into three groups of 20 subjects each. The first group consisted of patients with inevitable abortion. The second group included women with threatened abortion in whom pregnancy was maintained until term. The control group consisted of women with uncomplicated pregnancy. In all the patients venous blood was collected immediately after the diagnosis was settled and before the treatment was commenced. Two biochemical markers of oxidative stress were quantified, namely: lipid peroxides (LP) using spectrophotometric TBARS method and total antioxidant status (TAS) by means of the commercially available kits (TAS: Randox Laboratories Ltd., U.K.). The obtained results indicate that spontaneous abortion is accompanied by a profound disruption of the prooxidant-antioxidant homeostasis towards oxidative stress.

[Levels of fetal and plasma fibronectin in patients with cervical incompetence]. / Poziom fibronektyny plodowej i osoczowej u pacjentek z objawami niewydolnosci ciesniowo-szyjkowej.

In 45 gravidae (below 24 weeks) fetal fibronectin (fF) was measured in cervico-vaginal discharge and plasma fibronectin (pF) was evaluated in venous blood. Twenty women had cervical incompetence (CI) diagnosed and 25 healthy gravidae served as a control. The fF level in patients with CI (0.073 +/- 0.014 mg/ml) was significantly (p < 0.01) higher than that found in the control group (0.058 +/- 0.011 mg/ml). The same was true for pF (p < 0.001). A diagnostic value of fibronectin levels in patients suspected of cervical incompetence is suggested.

[Influence of premature rupture of fetal membranes on kynurenic acid concentration in umbilical cord blood]. / Ocena wplywu przedwczesnego odplywania plynu owodniowego na stezenia kwasu kynureninowego we krwi pepowinowej.

The aim of the study was to evaluate the influence of premature rupture of fetal membranes on kynurenic acid (KYNA) levels in venous and arterial umbilical cord blood of neonates. Statistically significant higher concentration of KYNA in umbilical arterial and venous blood in neonates of mothers with PROM lasting longer than 11 hours was observed. Increase of KYNA concentration in blood of such babies may be one of markers of developing infection.

[Zoonoses in reproductive medicine]. / Choroby odzwierzece w medycynie prokreacji.

After reviewing the importance of three zoonoses, namely toxoplasmosis, listeriosis and brucellosis, Authors focus on their experience in prophylactic treatment of the acquired toxoplasmosis in 72 gravidae with high risk pregnancy and the history of toxoplasmosis. Listeriosis and brucellosis currently seem not to bear a clinical significance as perinatal risk factors. Toxoplasmosis, however, should be taken into account a cases of unexplained pregnancy loss. The Authors' experience suggests the positive effect of the combined prophylactis antitoxoplasmic treatment in the selected cases.

[Pregnancy complicated by a neoplasmatic disease]. / Ciaza powiklana choroba nowotworowa.

The Author reviews the problem of neoplasmatic complications of pregnancy focusing mainly on genital tumors such as vulvar, vaginal, cervical, uterine, tubal and ovarian neoplasms as well as on other pelvic tumors originating from the bladder and bowel. Non-genital neoplasms such as breast cancer, Hodgkin's disease, non-Hodgkin lymphoma, leukemia, melanoma and thyroid cancer are also addressed. Literature data on the incidence of tumors in pregnant women are reviewed and the therapeutic options considering both the mother and the fetus are discussed. Management recommendations are given in cases when following the treatment a patient becomes pregnant again.

[Levels of proinflammatory cytokines (Il-1 alpha, Il-6, TNF-alpha) in the semen plasma of male partners of infertile couples]. / Poziom cytokin prozapalnych (IL-1 alpha, IL-6, TNF-alpha) w plazmie nasienia mezczyzn z par nie posiadajacych potomstwa.

In semen plasma of 46 male partners of infertile couples the levels of proinflammatory cytokines such as IL-1 alpha, IL-6, TNF-alpha were quantified. The studied group was divided according to the number of leucocytes in an ejaculate into two subgroups (> 10(6)/ml and below 10(6)/ml). The levels of the studied cytokines were significantly elevated (p < 0.05) in patients with higher leucocyte count in the ejaculate. Testing the immunologic markers may be helpful in diagnostic process considering male partners of infertile couples.

[Menopausal medicine of the threshold of the third millennium]. / Medycyna menopauzalna u progu trzeciego tysiaclecia.

The paper reviews most important trends in hormonal replacement therapy which have appeared in recent years. The tailored approach to HRT, introduction of new drugs and modification of established treatment regimes are the most probable directions in which menopausal medicine would develop in the years to come.

[Serum estradiol levels in early postoperative period after surgical castration--the influence of estrogen replacement therapy]. / Poziom estrogenemii we wczesnym okresie pooperacyjnym po obustronnej ooforektomii z uwzglednieniem wplywu przezskórnej estrogenowej terapii zastepczej.

In 40 premenopausal women who underwent TAH&BSO serum E2 levels were measured by means of RIA in 3 time points: before the operation, in the postoperative day 2 and in the postoperative day 3. In 20 of the subjects the ERT (transdermal estradiol 0.1 g/24 h) was introduced in the 2 postoperative day. In the postoperative day 2 the average serum E2 decreased by nearly 90% as compared to the preoperative values. Twenty four hours after the application of the transdermal E2 patch, the estradiol level returned to the values insignificantly different from the preoperative ones.

[Serum levels of proinflammatory cytokines in women with uterine myomas]. / Poziom cytokin prozapalnych w surowicy krwi kobiet z miesniakami macicy.

The levels of proinflammatory cytokines, namely IL-1 alpha, IL-6 and TNF-alpha were determined in blood serum of 26 women with uterine myomas and in 20 healthy controls. A significantly elevated concentration of IL-1 alpha was found in patients with uterine myomas. Levels of IL-6 and TNF-alpha were insignificantly higher in women with myomas. The obtained results indicate the possible role of IL-1 alpha in the pathogenesis of uterine myomas--further studies are needed to elucidate the role of proinflammatory cytokines in the proliferative disorders of myometrium.

[Dental care during pregnancy]. / Opieka stomatologiczna nad kobieta ciezarna.

In the paper authors discussed the importance of dental care during pregnancy, prophylactic methods, dental treatment procedures and the influence of oral health status on pregnancy and fetus.