Ranitidine does not impair oxidative or conjugative metabolism: noninteraction with antipyrine, diazepam, and lorazepam

Potential interactions of ranitidine with antipyrine, diazepam, and lorazepam were evaluated. Ten healthy male subjects were injected intravenously with antipyrine (1.2 gm), diazepam (10 mg), or lorazepam (2 mg) on two randomly assigned occasions, once in the otherwise drug-free state and once while concurrently taking a therapeutic ranitidine dose of 150 mg every 12 hr. Kinetic analysis for antipyrine showed no change in elimination t1/2 between trials (mean, 11.6 and 11.5 hr) with no change in volume of distribution (Vd) or total clearance (0.77 and 0.75 ml/min/kg). Diazepam analysis also showed unchanged t1/2 (32.3 and 28.9 hr) with no change in Vd or total clearance (0.42 and 0.39 ml/min/kg). Lorazepam as well had unchanged t1/2 (11.7 and 11.3 hr), Vd, and total clearance (1.52 and 1.65 ml/min/kg). Therefore ranitidine, unlike cimetidine, has no effect on either human hepatic drug oxidation, as measured by antipyrine and diazepam clearance, or human drug conjugation, as measured by lorazepam clearance.     

Endothelin-I-mediated vasoconstriction: specific blockade by verapamil.

The capacity of three vasodilators that act by distinct mechanisms to reverse endothelin-I-mediated vasoconstriction was studied in 11 healthy nonsmoking male subjects (mean age +/- SEM, 26 +/- 2 years; mean weight +/- SEM, 74 +/- 2 kg) by use of brachial artery infusion and forearm strain-gauge plethysmography. Isoproterenol (cyclic adenosine monophosphate-mediated vasodilation), sodium nitroprusside (cyclic guanosine monophosphate-mediated vasodilation), and verapamil (L-type calcium channel blocker) were compared for capacity to reverse endothelin-I-mediated increase in forearm vascular resistance (FVR). Endothelin-I infusion increased FVR 1.9-fold in the control state. Isoproterenol infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable isoproterenol infusion rates, endothelin-I increased FVR similar to the control state (for 5 ng/min isoproterenol, endothelin-I increased FVR 1.85-fold; for 12.5 ng/min isoproterenol, endothelin-I increased FVR 2.03-fold). Similarly, sodium nitroprusside infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable sodium nitroprusside infusion rates the endothelin-I increase in FVR was similar to control (for 0.48 micrograms/min sodium nitroprusside, endothelin-I increased FVR 1.89-fold; for 0.96 micrograms/min sodium nitroprusside, endothelin-I increased FVR 2.36-fold). In contrast, verapamil infusion decreased FVR with or without endothelin-I infusion. At a verapamil infusion rate of 19.1 microns/min, endothelin-I increase in FVR was comparable to control (for 19.1 microns/min verapamil, endothelin-I increased FVR 1.36-fold, less than the 1.0-fold increase in the control state; p < 0.05). Isoproterenol and sodium nitroprusside decreased FVR during concurrent endothelin-I infusion but did not reverse the endothelin-I effect. In contrast, verapamil reversed endothelin-I--induced vasoconstriction to control FVR, suggesting a specific antagonism of endothelin-I--mediated increase in FVR.     

Options for the treatment of menopausal symptoms

Many women experience unpleasant symptoms about the time of the menopause and after, for which a range of treatments is available. This article discusses their efficacy and safety.     

Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia

Reported here are studies of Fanconi anemia fetal cells that led to the first use of umbilical cord blood for hematopoietic reconstitution in a clinical trial. Prenatal diagnosis and HLA typing were performed in fetuses at risk for Fanconi anemia (FA) to identify, prior to birth, those that were unaffected with the syndrome and were HLA-identical to affected siblings. Umbilical cord blood was harvested at the delivery of these infants; assays of progenitor cells indicated the presence of colony-forming units-granulocyte-macrophage (CFU-GM) in numbers similar to those of bone marrow CFU-GM that are associated with successful engraftment in HLA-matched allogeneic bone marrow transplantation. The possibility that umbilical cord blood from a single individual can be used as an alternative to bone marrow for hematopoietic reconstitution has now been demonstrated by the successful engraftment of two patients with FA. Progenitor cell assays of umbilical cord blood collected at the birth of a child affected with FA, who had been misdiagnosed on the basis of chorionic villus sampling (CVS) studies, indicated a profound deficiency in colony formation, consistent with previously reported abnormalities in the growth of FA cells in vitro. These results suggest that the hematopoietic disorder in FA is related to an underlying problem with cell proliferation.     

Informatics in action: lessons learned in comparative effectiveness research

Comparative effectiveness research (CER) is meant to provide evidence about the relative risks and benefits of different treatment options. It is gaining visibility as a tool to address the evidence gaps that clinicians struggle with every day; however, CER is particularly challenging in oncology as there is great variability in how individuals respond to interventions, and a wide range of drugs and procedures are available. In order to overcome these obstacles and conduct reliable CER studies, it is critical to create a robust data infrastructure to support it.The Center for Medical Technology Policy held its first annual CER Summit in November 2010, with a particular focus on oncology. A number of critical informatics themes emerged including the need for consistent data standards, registry reform, tools to assist trial accrual, and data to integrate into value deliberations. Addressing the data issues highlighted in this report will provide a significant opportunity to improve the health of our medical system.     

Electronic toxicity monitoring and patient-reported outcomes

Understanding the potential profile of adverse events associated with cancer treatment is essential in balancing safety versus benefits. Multiple stakeholders make use of this information for decision making, including patients, clinicians, researchers, regulators, and payors. Currently, adverse events are reported by clinical research staff, yet evidence suggests that this may contribute to underreporting of symptom events. Direct patient reporting via electronic interfaces offers a promising mechanism to enhance the efficiency and precision of our current approach and may complement clinician reports of adverse events. The National Cancer Institute has contracted to develop and test an item bank and software system for directly eliciting adverse symptom event information from patients in cancer clinical research, called the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events. The validity, usability, and scalability of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events prototype are currently being examined in academic and community-based settings.     

The Value of Data Collection within a Palliative Care Program

Collecting reliable and valid data is an increasing expectation within palliative care. Data remain the crux for demonstrating value and quality of care, which are the critical steps to program sustainability. Parallel goals of conducting research and performing quality assessment and improvement can also ensure program growth, financial health, and viability in an increasingly competitive environment. Mounting expectations by patients, hospitals, and payers and inevitable pay-for-performance paradigms have transitioned data collection procedures from novel projects to expected standard operation within usual palliative care delivery. We present types of data to collect, published guides for data collection, and how data can inform quality, value, and research within a palliative care organization. Our experiences with the Quality Data Collection Tool (QDACT) in the Carolinas Palliative Care Consortium to collect data on quality have led to valuable lessons learned in creating a data collection system. Suggested steps in forming data-sharing collaborations and building data collection procedures are shared.