Thrombocytosis in children.

In healthy pediatric subjects normal count platelet ranges between 250,000 μL and 450,000 μL. An elevated platelet count greater than 2 SD defines a condition of thrombocytosis. On a clinical level, thrombocytosis is classified "mild" at a platelet count between >500,000 μL and <700,000 μL; "moderate" at a platelet count between >700,000/μL and <900,000/μL; "severe" at a platelet count >900,000/μL; and "extreme" at a platelet count >1,000,000/μL.

Biphenyl sulfonylamino methyl bisphosphonic acids as inhibitors of matrix metalloproteinases and bone resorption.

A number of matrix metalloproteinases (MMPs), proteins important in the balance of bone remodeling, play a critical role both in cancer metastasis and in bone matrix turnover associated with the presence of cancer cells in bone. Here, we report the synthesis and biological evaluation of a new class of MMP inhibitors characterized by a bisphosphonate function as the zinc binding group. Since the bisphosphonate group is also implicated in osteoclast inhibition and provides a preferential affinity to biological apatite, the new molecules can be regarded as bone-seeking medicinal agents.

Identification of novel matrix metalloproteinase inhibitors by screening of phenol fragments library.

In the last 20 years, a great variety of synthetic, low molecular weight MMP inhibitors (MMPIs) have been synthesized and tested, although none has reached clinical utility. Exploration of novel ZBGs and development of non-hydroxamate MMPI has become a focus in current research. It's well-known that polyphenols can produce beneficial effects on human health by their antioxidant properties as well as they have the ability to block gelatinase activity.

A comparison of daily average consumption (DACON) of oxycodone and oxymorphone long-acting oral tablets.

Background: The utilization of high-potency opioids is an important component of chronic pain management, and appropriate utilization of these medicines is a common concern of payers. Two of the most commonly prescribed oral long-acting opioids, oxycodone controlled-release (CR) and oxymorphone extended-release (ER), are FDA-approved for twice-daily dosing, which equates to a theoretical average consumption (DACON) of 2 tablets per day. DACON values greater than 2 have budget and policy implications for managed care pharmacists.

NCCN Oncology Risk Evaluation and Mitigation Strategies White Paper: Recommendations for Stakeholders.

REMS are a particularly important issue for oncology and the National Comprehensive Cancer Network (NCCN). A disproportionate number of drugs with complex REMS are used in patients with cancer or hematologic disorders. REMS policies and processes within oncology may act as a model for other clinical areas.

Raw materials case histories.

This paper describes three case studies involving the handling of raw materials. One case study deals with animal-derived materials. The other two case studies demonstrate the need to also focus on raw materials with regard to recombinant bacterial-derived products.

Experiences with HEK293: A Human Cell Line.

The paper describes considerations taken with regard to a recombinant human cell line (HEK293) producing a therapeutic protein. When working with HEK293 cells, besides standard viral safety issues, special precautions should be taken because this cell line is susceptible to infection by numerous viruses. A viral contamination event occurred with this cell line even after a number of precautions were taken.

Peritoneal surface malignancies and regional treatment: a review of the literature.

Recent studies have lead to a renewed interest in cytoreductive surgery and intraperitoneal chemotherapy as a regional treatment modality for patients with peritoneal surface malignancies. There have been multiple phase III randomized trials that have shown a survival advantage with intraperitoneal chemotherapy in certain patients. More well designed phase III studies are needed to further define which groups of patients may benefit from cytoreductive surgery and intraperitoneal chemotherapy.

Acute hyperglycemia and contrast-induced nephropathy in primary percutaneous coronary intervention.

Background: Acute hyperglycemia and contrast-induced nephropathy (CIN) are frequently observed in ST-elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), and both are associated with an increased mortality rate. We investigated the possible association between acute hyperglycemia and CIN in patients undergoing primary PCI.

Methods: We prospectively enrolled 780 STEMI patients undergoing primary PCI.

Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice.

Background: Dietary (n-6)-polyunsaturated fatty acids influence cancer development, but the mechanisms have not been well characterised in gastric carcinoma.

Methods: We used two in vivo models to investigate the effects of these common dietary components on tumour metastasis. In a model of experimental metastasis, immunocompromised mice were fed diets containing linoleic acid (LA) at 2% (LLA), 8% (HLA) or 12% (VHLA) by weight and inoculated intraperitoneally (i.

Investigation on the phototransformation of tadalafil in aqueous media. 6-Epimerization vs. solvent trapping reaction.

Irradiation of tadalafil at lambda > 290 nm in aqueous solutions leads to 6-epimer and/or water adducts depending on concentration and pH. A rationalization of the results involves the heterolytic cleavage of C6-N5 bond via a well-stabilized zwitterionic intermediate. The drug is stable in the dark except under strongly basic conditions where it undergoes C12a-epimerization.

Circulating microRNAs are new and sensitive biomarkers of myocardial infarction.

Aims: Circulating microRNAs (miRNAs) may represent a novel class of biomarkers; therefore, we examined whether acute myocardial infarction (MI) modulates miRNAs plasma levels in humans and mice.

Methods And Results: Healthy donors (n = 17) and patients (n = 33) with acute ST-segment elevation MI (STEMI) were evaluated. In one cohort (n = 25), the first plasma sample was obtained 517 ± 309 min after the onset of MI symptoms and after coronary reperfusion with percutaneous coronary intervention (PCI); miR-1, -133a, -133b, and -499-5p were ~15- to 140-fold control, whereas miR-122 and -375 were ~87-90% lower than control; 5 days later, miR-1, -133a, -133b, -499-5p, and -375 were back to baseline, whereas miR-122 remained lower than control through Day 30.

Isotopic evidences for microbiologically mediated and direct C input to soil compounds from three different leaf litters during their decomposition.

We show the potentiality of coupling together different compound-specific isotopic analyses in a laboratory experiment, where (13)C-depleted leaf litter was incubated on a (13)C-enriched soil. The aim of our study was to identify the soil compounds where the C derived from three different litter species is retained. Three (13)C-depleted leaf litter (Liquidambar styraciflua L.

Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy.

Objectives: The purpose of this study was to evaluate the clinical relevance of anthracycline-induced cardiomyopathy (AC-CMP) and its response to heart failure (HF) therapy.

Background: The natural history of AC-CMP, as well as its response to modern HF therapy, remains poorly defined. Hence, evidence-based recommendations for management of this form of cardiomyopathy are still lacking.

Acute kidney injury in ST-segment elevation acute myocardial infarction complicated by cardiogenic shock at admission.

Objective: To evaluate the clinical and prognostic relevance of acute kidney injury (AKI) in the setting of ST-elevation acute myocardial infarction (STEMI) complicated by cardiogenic shock (CS).

Design: Prospective study.

Setting: Single-center study, 13-bed intensive cardiac care unit at a University Cardiological Center.

Arachidonic acid stimulates cell adhesion through a novel p38 MAPK-RhoA signaling pathway that involves heat shock protein 27.

Rho GTPases are critical components of cellular signal transduction pathways. Both hyperactivity and overexpression of these proteins have been observed in human cancers and have been implicated as important factors in metastasis. We previously showed that dietary n-6 fatty acids increase cancer cell adhesion to extracellular matrix proteins, such as type IV collagen.

Giant congenital aortic aneurysm with cleft sternum in a neonate: pathological and surgical considerations for optimal management.

We report a rare case of a neonate with congenital giant aortic aneurysm associated to cleft sternum, who underwent surgical repair. The patient died on postoperative Day 5 from cardiac arrest. Autopsy revealed a circumferential subendocardial myocardial infarction and misdiagnosed coronary ostial anomalies.

Synthesis, SAR, and biological evaluation of alpha-sulfonylphosphonic acids as selective matrix metalloproteinase inhibitors.

Eleven simple alpha-sulfonylphosphonates, new analogues of previously reported alpha-sulfonylaminophosphonates, were prepared and tested as MMP inhibitors. The IC(50) values of most of these compounds are in the nanomolar range against MMP-2, -8, -13, and -14. Compound 11 proved to be the most effective inhibitor of MMP-2 (IC(50) = 60 nM), with interesting selectivity versus the antitarget enzymes MMP-3 and MMP-9.

Contrast volume during primary percutaneous coronary intervention and subsequent contrast-induced nephropathy and mortality.

Background: Contrast-induced nephropathy (CIN) frequently occurs in patients with acute ST-segment elevation myocardial infarction (STEMI) who are undergoing primary percutaneous coronary intervention, and CIN is associated with a more complicated clinical course and increased mortality.

Objective: To investigate the association between absolute and weight- and creatinine-adjusted contrast volume, CIN incidence, and clinical outcome in the era of mechanical reperfusion of STEMI.

Design: Prospective, observational study.

Postharvest shelf life extension of blueberries using a biodegradable package.

Small berries are commonly packaged and sold to consumers in vented petroleum-based clamshell containers. Biodegradable and compostable packages may be used as an alternative package to reduce waste generation and landfill disposal. In addition, the current clamshell container design does not allow the development of a modified atmosphere that could prolong berry shelf life.

Rationale and design of the Post-MI FREEE trial: a randomized evaluation of first-dollar drug coverage for post-myocardial infarction secondary preventive therapies.

Background: Medication nonadherence is a major public health problem, especially for patients with coronary artery disease. The cost of prescription drugs is a central reason for nonadherence, even for patients with drug insurance. Removing patient out-of-pocket drug costs may increase adherence, improve clinical outcomes, and even reduce overall health costs for high-risk patients.

High-resolution sonography of the palmar cutaneous branch of the median nerve.

Objective: The aim of this study was to describe the potential value of high-resolution sonography for evaluation of the palmar cutaneous branch of the median nerve (MN).

Subjects And Methods: The volar wrists of 12 healthy volunteers and 22 consecutive patients with sensory deficit in the palmar triangle and thenar eminence suggesting neuropathy of the palmar cutaneous branch of the MN were examined with high-frequency sonography. Nine patients underwent carpal tunnel release, five had a history of penetrating trauma, six had symptoms suggesting concurrent carpal tunnel syndrome, one received surgery for palmaris tendon transfer, and one underwent resection of a ventral carpal ganglion cyst.

NCCN Task Force Report: Oral chemotherapy.

Oral chemotherapy is emerging as a new option for well-selected patients who can manage potentially complex oral regimens and self-monitor for potential complications. If a choice between oral and parenteral therapy is available, patients may opt for oral chemotherapy because it is more convenient to administer, allows them to avoid multiple office visits, and gives them a sense of control over their own cancer care. Whether these potential advantages are maintained in regimens that combine oral and parenteral drugs is less clear.