The relationship between weight gain during chemotherapy and outcomes in patients with advanced non-small cell lung cancer.

Background: This post hoc, pooled analysis examined the relationship between different weight gain categories and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving first-line platinum-based chemotherapy.

Methods: Data were pooled from the control arms of three phase III clinical studies (NCT00596830, NCT00254891, and NCT00254904), and the maximum weight gain in the first 3 months from treatment initiation was categorised as >0%, >2.5%, and >5.

Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study.

Background: PF-05280014 was compared with trastuzumab sourced from the European Union (trastuzumab-EU), each plus paclitaxel, as first-line treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer in a phase III study. Equivalence between treatment groups was demonstrated.

Objective: The aim of this study was to report long-term safety and overall survival (OS) over 6 years after the first patient was screened.

PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study.

Background: PF-06439535 is a bevacizumab biosimilar. We aimed to compare the efficacy and safety of PF-06439535 with that of reference bevacizumab (Avastin) sourced from the EU (bevacizumab-EU), each with paclitaxel and carboplatin, in the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods: In this double-blind, parallel-group study, we recruited patients from 159 centers in 27 countries.

An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study).

Background: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice.

Objective: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week.

Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer.

Background: This randomised, double-blind study compared pharmacokinetics, efficacy, safety and immunogenicity of PF-05280014 (potential trastuzumab biosimilar) and trastuzumab reference product (Herceptin) sourced from the European Union (trastuzumab-EU) as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Methods: Patients (N = 226), stratified by primary tumour size and hormone receptor status, were randomised 1:1 to PF-05280014 or trastuzumab-EU (8 mg/kg loading dose; 6 mg/kg thereafter), each with docetaxel and carboplatin, every 3 weeks for six treatment cycles. Primary endpoint was percentage of patients with trough plasma concentration (C) >20 μg/ml at Cycle 5 (Cycle 6 predose).

The role of training in effective simulated self-injection of subcutaneous depot medroxyprogesterone acetate: observations from a usability study.

Objectives: The need for quarterly clinic visits is a barrier to use of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) contraception. The ability to self-inject at home may enhance method acceptance. Since efficacy depends on proper administration, we evaluated whether women could correctly perform simulated injections of DMPA-SC in a Uniject™ injection system using printed Instructions for Use (IFU), with and without hands-on training.

Postcesarean pulmonary embolism, sustained cardiopulmonary resuscitation, embolectomy, and near-death experience.

Background: Survival after surgical embolectomy for massive postcesarean pulmonary embolism causing sustained cardiac arrest is rare.

Case: One day after an uneventful cesarean delivery, a woman developed cardiac asystole and apnea due to pulmonary embolism. Femoral-femoral cardiopulmonary bypass performed during continuous cardiopulmonary resuscitation allowed a successful embolectomy.

Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.

Background: Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients.

Methods: Non-neutropenic patients with a positive blood culture for a species of candida and clinical evidence of infection were enrolled.

The effect of tyrosine-deficient total parenteral nutrition on the synthesis of dihydroxyphenylalanine in neural tissue and the activities of tyrosine and branched-chain aminotransferases.

The poor solubility of tyrosine (Tyr) limits the amount of this amino acid in total parenteral nutrition (TPN). In rats maintained on a standard pediatric TPN mixture, plasma and brain concentrations of Tyr are reduced to about 25% of the levels in chow-fed controls. To determine whether these low concentrations of Tyr affect the synthesis of catecholamines in neural tissue, the rate-limiting step (conversion of Tyr to dihydroxyphenylalanine [DOPA]) is studied by administering NSD-1015 to block the pyridoxal phosphate (PLP)-dependent decarboxylation of DOPA.

Melatonin rhythms and pineal structure in a tropical bat, Anoura geoffroyi, that does not use photoperiod to regulate seasonal reproduction.

It has been hypothesized that pineal structure and function might differ between temperate zone and tropical species of mammals because of lower amplitudes of seasonal change in photoperiod and, in some areas, less seasonal climatic variation. Anoura geoffroyi produce a single offspring in November or December of each year on the Caribbean island of Trinidad, at 10 degrees N latitude in the deep tropics. Previous work has shown that this population lacks reproductive responses to photoperiod, and must be enforcing seasonal breeding using a non-photoperiodic cue.

Intravenous gamma-glutamyl-tyrosine elevates brain tyrosine but not catecholamine concentrations in normal rats.

A number of clinical situations may benefit from intravenous supplements of tyrosine (Tyr). In total parenteral nutrition (TPN), the supply of Tyr is limited by its poor solubility. In both rats and infants maintained on pediatric TPN, plasma Tyr levels are approximately 30% of normal, and in rat brains Tyr concentrations are similarly reduced.

Observations on the pineal gland of the big brown bat, Eptesicus fucus: possible correlation of melanin intensification with constant darkness.

Background: Our initial observation of the macroscopically pigmented pineal gland of the big brown bat, Eptesicus fuscus, led to this study. Information has been lacking on pigmentation in the pineal and its significance in mammals in general and bats in particular. This report begins to address this situation.

Use of the soluble peptide gamma-L-glutamyl-L-tyrosine to provide tyrosine in total parenteral nutrition in rats.

Limited solubility restricts amounts of tyrosine (Tyr) in amino acid solutions used in total parenteral nutrition (TPN). Excess phenylalanine (Phe) is included in TPN for conversion to Tyr by liver Phe hydroxylase. However, this conversion is limited, especially in infants.

Use of the stable peptide, gamma-L-glutamyl-L-tyrosine, as an intravenous source of tyrosine in mice.

The relative insolubility of tyrosine (Tyr) at neutral pH limits amounts of this amino acid in solutions used for total parenteral nutrition (TPN). We have tested the potential of the natural peptide, gamma-L-glutamyl-L-tyrosine (Glu(Tyr], to release Tyr in vivo by making 20-microL injections, containing 2.9 mumol Glu(Tyr) (approximately 80 mumol/kg body weight), into the external jugular veins of mice.

Repeatability and protocol comparability of presyncopal symptom limited lower body negative pressure exposures.

Data on repeatability and comparability of different presyncopal symptom-limited lower body negative pressure (PSL-LBNP) exposure protocols, while scarce, are critical to the interpretation of studies using PSL-LBNP methods. To investigate if PSL-LBNP tolerance, heart rate, and blood pressure were repeatable, 11 subjects were exposed to 4 PSL-LBNP tests; each test occurring at the same time of day, separated by at least 72 h, and using the same protocol. No significant differences were found in either the heart rate or blood pressure responses to the PSL-LBNP or the tolerance indices (cumulative stress index; maximum negative pressure tolerated; and duration of negative pressure exposure).

Record linkage: statistical models for matching computer records.

"We wish to measure the evidence that a pair of records relates to the same, rather than different, individuals. The paper emphasizes statistical models which can be fitted to a file of record pairs known to be correctly matched, and then used to estimate likelihood ratios. A number of models are developed and applied to U.

Increased binding of epidermal growth factor at preimplantation sites in mouse uteri.

The presence of receptors for epidermal growth factor (EGF) in nonpregnant uteri and the elevation of EGF levels in blood during early pregnancy suggest that EGF and its receptor may play important roles in the early stages of pregnancy. We determined the distribution of EGF receptors in uteri of nonpregnant and pregnant mice during the late preimplantation period (days 4.5-5.

Vasodepressor syncope induced by lower body negative pressure: possible relevance to +Gz-stress training--a case report.

We present a case report of vasodepressor syncope with brief sinus pause in a 26-year-old male subject following a graded lower body negative pressure (LBNP) challenge culminating at -70 mm Hg. Cessation of the LBNP protocol resulted in the return of heart rate and blood pressure activity to pre-challenge levels. Sinus arrest during central hypovolemic stress has been noted in the literature.

Intrauterine position affects sex-accessory biochemistry in adult female mice.

Female mouse fetuses that develop in utero implanted between two male fetuses (2M females) are shown as adults to have significantly elevated (P less than 0.01) levels of beta-glucuronidase activity in their preputial glands compared to that of OM females, females that had not been contiguous to males in utero, and 1M females, females contiguous in utero to only one male (mean +/- SEM, 2M females = 23,9 +/- 2.1, 1M females = 13.

Effect of hypoxic hypoxia on taurine concentrations in ventricles of mouse hearts.

The effects of hypoxic hypoxia on the concentration of taurine in right ventricles was studied in the hearts of male CF1 mice caged individually and maintained for 16 hr per day in a hypobaric chamber evacuated to an air pressure of 307 mm Hg. After 23 days hearts were excised and right and left ventricles were separated and lyophilized. Hematocrits in chamber animals were 77-82%, compared to 45-49% for control mice.

Intrauterine proximity to male fetuses predetermines level of epidermal growth factor in submandibular glands of adult female mice.

Morphological, behavioral, and physiological masculinization of adult female mice that developed in utero between two male fetuses (2M females) has been previously attributed to the significantly higher concentration of testosterone in their fetal blood and amniotic fluid than that in female mice which had not been contiguous to males in utero (0M females). Serum testosterone levels of adult 2M and 0M females are not significantly different. To determine whether exposure of fetuses to different levels of testosterone during prenatal development alters adult biochemical parameters of a system responsive to testosterone, the level of epidermal growth factor (EGF) was measured by radioreceptor assay in the submandibular glands of adult CF-1 mice of known intrauterine position.

Taurine in hearts and bodies of embryonic through early postpartum CF1 mice.

The hearts and remaining bodies of embryonic and fetal mice of known gestational age and of neonatal mice up to the age of 8.5 days were freeze-dried, weighed, and analyzed for the amino acid, taurine, by high performance liquid chromatography. Although cardiac taurine is only a small fraction of the taurine in the rest of the body in all animals studied, the concentration of taurine in the heart is similar to that in the rest of the body (40-45 nmole/mg freeze-dried wt) in embryos through Day 14.

Further evidence for behaviorly induced hypoxic conditions in subordinate mice.

When two male mice fight to establish social rank, the subordinate exhibits marked splenomegaly, reticulocytosis and decreased hematocrit. Individuals were isolated at weaning, paired 3 weeks later for two 30-min encounter periods daily for up to 3 weeks. After 2 days and 1 week encounter periods, subordinates had significantly decreased levels of hemoglobin in the kidney compared to dominants and controls.

Changes in concentrations of taurine in murine Harderian glands and retinas during postnatal development.

Quantitative measurements of taurine in the Harderian glands of male and female CF-1 mice were made by standard methods of amino acid analysis. Values, in nmoles per mg dry weight of gland, were 60 to 70 in the first 4 postnatal days with a gradual decrease to 31.1 +/- 3.