Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

Background: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study.

UROLITH PREVALENCE AND RISK FACTORS IN ASIAN SMALL-CLAWED OTTERS ( AONYX CINEREUS).

Uroliths (urinary stones) are routinely found in both domestic and exotic animals kept under human care. In zoos, Asian small-clawed otters (ASCOs, Aonyx cinereus) have been identified as being particularly prone to this disease. Risk factors are thought to be nutritional; however, recommendations contradict each other, depending on which physiological model was used.

A Phase II and Biomarker Study of Sorafenib Combined with Modified FOLFOX in Patients with Advanced Hepatocellular Carcinoma.

Purpose: Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma (HCC). The phase III SHARP trial showed a median time-to-progression (mTTP) of 5.5 months, overall response rate (ORR) of 2%, and median overall survival (mOS) of 10.

Management support, worksite culture, and local resources for healthier employees: the Veterans Affairs experience.

Objective: To determine whether a "worksite culture of health" exists within the Veterans Health Administration and implications on integrating employee health promotion programs.

Methods: Three national surveys were used-an organizational health survey, a health behaviors survey, and a worksite environment survey. Cross-sectional associations between measures of organizational health and employee health behaviors and between measures of organizational health and worksite environment were assessed.

[Inhibitory effect of interleukin-1 beta on follicle stimulating hormone (FSH) induced estrogen production by cultured rat granulosa cells].

Interleukin-1 beta (IL-1 beta), one of the polypeptide lymphokines released in response to antigen, toxins, injury or inflammation by nearly all cell types, has multiple systemic effects. In the present study the effect of IL-1 beta on follicle stimulating hormone (FSH)-induced estrogen production in primary culture was investigated. Granulosa cells obtained from immature estrogen-treated female rats were cultured for 3 days with increasing doses of FSH (1-30 ng/ml) with or without increasing doses of IL-1 beta (2-20 U/ml).

Recombinant follicle-stimulating hormone induces ovulation and tissue plasminogen activator expression in hypophysectomized rats.

Ovulation in mammals is preceded by surges of the two pituitary gonadotropins, LH and FSH. Although previous studies have shown that purified FSH induces ovulation when administered to hypophysectomized rats, proof that FSH has inherent ovulatory potential is lacking because all FSH preparations have varying degrees of residual LH. To determine if FSH alone can induce ovulation, we generated LH-free recombinant FSH (RCFSH) by culturing eukaryotic cells transfected with the human common alpha- and FSH beta-subunit genes.

Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone.

Gonadotroph adenomas may exhibit qualitative and quantitative defects in gonadotropin biosynthesis and secretion. Hypersecretion of immunoreactive FSH dimers by these adenomas occurs frequently; however, it has not been known whether this FSH is biologically active. Using the granulosa cell aromatase bioassay and a highly specific immunoradiometric assay for FSH, we studied the serum bioactivity and bio- to immunoactivity (B/I) ratios of 14 men with FSH-secreting adenomas and compared these values to those of 11 age-matched normal men.

In vitro and in vivo bioactivity of recombinant human follicle-stimulating hormone and partially deglycosylated variants secreted by transfected eukaryotic cell lines.

Recent studies have shown that Chinese hamster ovary (CHO) cells transfected with the FSH subunit genes secrete bioactive FSH. Here, we determined the in vitro and in vivo bioactivity of recombinant FSH produced by CHO mutant cells deficient in the glycosylation enzyme N-acetylglucosamine transferase-I (NAGT-), resulting in glycoproteins with asparagine-linked (GlcNAc)2(Mannose)5 oligosaccharides, or mutant cells defective in sialic acid transport into the Golgi (ST-). In the latter, glycoproteins are secreted lacking terminal sialic acids.

Epidermal growth factor stimulates tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells: mediation by pathways independent of protein kinases-A and -C.

Recent reports suggest that epidermal growth factor (EGF) or related peptides may act as local hormones to regulate granulosa cell differentiation. While FSH and GnRH are known to stimulate accumulation of tissue-type plasminogen activator (tPA) mRNA in granulosa cells, studies using nonovarian cells have shown stimulation of tPA by EGF. In this study, the effect of EGF and its structural analog transforming growth factor-alpha (TGF alpha) on ovarian tPA mRNA and activity was investigated.

Inhibitory actions of interleukin-1 beta on steroidogenesis in primary cultures of neonatal rat testicular cells.

Interleukin-1 is an important cytokine produced by activated macrophages. Because macrophages have been localized in the testis and interleukin-1 bioactivity has been observed in the testis, the potential effect of interleukin-1 on gonadotropin-stimulated androgen production was investigated using primary cultures of neonatal rat testis cells. Cells were incubated for 3 days before change of medium and treatment with human chorionic gonadotropin and interleukin-1.

Expression of biologically active human follitropin in Chinese hamster ovary cells.

To study the structure-function relationships of follitropin (FSH), we expressed the hormone in a heterologous cell system. A genomic clone bearing a 3.7-kilobase FSH beta insert containing the entire coding sequence was transfected alone or together with the alpha subunit gene into Chinese hamster ovary cells and stable lines expressing either FSH beta or FSH dimer were selected.

Increased metabolic heat production following chronic alpha-methyldopa therapy in hypertensives.

The objective of this study was to measure metabolic heat production in mild-moderate hypertensives when given chronic alpha-methyldopa for control of hypertension and to compare this with hydrochlorothiazide. Four men and one woman, age range 29-55 years, euthyroid, and not previously on alpha-methyldopa, had their drugs replaced by placebo for 4 weeks, and then alpha-methyldopa or hydrochlorothiazide was randomized single blindly to patients. The dose of each drug was increased until the ambulatory diastolic blood pressure was less than 95 mmHg (1 mmHg = 133.

An appraisal of antihypertensive efficacy and adverse reactions with two drug regimens: enalapril maleate as part of triple therapy compared to conventional triple therapy in moderate to severe hypertension.

A randomized, double-blind, parallel treatment trial was carried out in 24 patients with moderate to severe hypertension to compare the effectiveness and tolerance of two treatment regimens in reducing and maintaining supine diastolic blood pressure below 90 mmHg. Patients in Group I received 10 to 40 mg enalapril maleate per day with the addition of 50 mg hydrochlorothiazide per day and then 250 to 1000 mg alpha-methyldopa per day, if necessary. Patients in Group II received 50 mg hydrochlorothiazide per day with the addition of 80 to 240 mg propranolol and then 100 to 200 mg hydralazine per day, if necessary.

Separation of essential hypertensive patients based on blood pressure responses after the withdrawal of antihypertensive agents by step-wise discriminant analysis.

Thirty-five patients with uncomplicated hypertension were observed for blood pressure behaviour after prolonged antihypertensive medication withdrawal. Twenty-three patients (Group 1) remained normotensive (systolic less than 140 mmHg, diastolic less than 95 mmHg) for over 60 weeks compared to 12 patients (Group 2) who became hypertensive again during a 4-week placebo period. Discriminant analysis was performed on 31 clinical and laboratory variables measured before therapy to separate any discriminating factors for the two groups.

Prolonged normotension following cessation of therapy in uncomplicated essential hypertension.

The blood pressure levels of 17 men and 7 women aged 27-65 years with uncomplicated essential hypertension were studied during and after withdrawal of antihypertensive therapy. Medication during the treatment phase included diuretics alone (13 patients), diuretic-nondiuretic combinations (5 patients), and nondiuretics alone (6 patients). Blood pressures were followed: greater than 48 weeks (with therapy) vs greater than 48 weeks (without therapy).

Potassium conservation with amiloride/hydrochlorothiazide ("Moduret') in thiazide-induced hypokalaemia in hypertension.

A double-blind study was carried out in 24 hypertensive patients with thiazide-induced hypokalaemia (serum potassium less than 3.2 mmol/l) to compare the effects of treatment with an amiloride/hydrochlorothiazide combination or hydrochlorothiazide alone. The study was divided into three phases: (i) potassium repletion (Weeks 0 to 4) with oral potassium chloride (40 mmol/day), (ii) stabilization (Weeks 4 to 6) of normokalaemia, and (iii) active drug treatment (Weeks 6 to 14), patients being allocated at random to receive one or other of the two treatments.

Comparison of antihypertensive efficacy: propranolol versus oxprenolol in accelerated hypertension.

An open, randomized crossover study was carried out in 8 patients with accelerated hypertension to compare the antihypertensive efficacy of oxprenolol with that of propranolol. Dosage was titrated for each patient to achieve normotensive levels and was in the range of 40 to 320 mg twice daily. The same mg dosage was maintained for the alternative drug after crossover at 32 weeks for the second treatment period.