Do bcl‐2 and survivin help distinguish benign from malignant B‐cell lymphoid aggregates in bone marrow biopsies?

Bcl-2 and survivin are cellular proteins that are known to be inhibitors of apoptosis and are commonly found in malignant tissues, including lymphomas. In previous studies, it has been shown that staining for bcl-2 can help distinguish between benign and malignant lymphoid aggregates in bone marrow biopsies. To determine whether staining for survivin expression in lymphoid aggregates can aid investigators in making this clinically important distinction, we stained bone marrow biopsies from 10 patients with benign lymphoid aggregates, and 15 malignant ones derived from B cells (six mantle cell, four follicular cells, two diffuse large cell, two small lymphocytic cell, and one marginal zone lymphoma) with antibodies to CD3, CD20, bcl-2, and survivin by an indirect immunoperoxidase technique. Whereas staining for bcl-2 was significantly stronger in the malignant lymphoid aggregates (P=0.001), both the control and malignant cases were almost uniformly negative for survivin expression. Only three cases (two mantle cell and one small lymphocytic lymphoma) showed very faint expression of survivin. Although bcl-2 and survivin both act to inhibit apoptosis, their expressions do not parallel each other. Survivin is not significantly expressed in either benign or malignant bone marrow aggregates, and therefore measuring its expression does not help distinguish benign from malignant B-cell bone marrow lymphoid aggregates.     

An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors

RATIONALE, AIMS AND OBJECTIVES: To identify potential factors leading to discontinuation of angiotensin-converting enzyme (ACE) inhibitors because of adverse drug events. METHODS: Retrospective cohort study was conducted at outpatient clinics affiliated with an urban tertiary care hospital. ACE inhibitors were administered to 2225 consecutive outpatients. RESULTS: In 19% of the total cohort, ACE inhibitors were discontinued because of adverse drug events. Cox proportional hazard model identified the following independent risk factors for discontinuation because of adverse drug events: age, female gender, ethnicity other than African American or Latino, no history of previous ACE inhibitor use, history of cough caused by another ACE inhibitor, hypertension, anxiety or depression, no hemodialysis, and elevated creatinine. History of smoking was shown to be a risk factor for cough [hazard ratio (HR): 2.5; 95% confidence interval (CI): 1.1-5.7], angioedema (HR: 2.7; 95% CI: 1.1-7.0), and hyperkalaemia (HR: 5.4; 95% CI: 1.3-23.2). History of ACE inhibitor-induced cough was not only a risk factor for cough (HR: 12.9; 95% CI: 7.5-22.3) but also for angioedema (HR: 9.1; 95% CI: 2.1-39.9). Patients with creatinine > or = 1.6 mg dL(-1) were likely to discontinue ACE inhibitors because of renal dysfunction (HR: 4.7; 95% CI: 1.5-12.7) and hyperkalaemia (HR: 10.9; 95% CI: 3.1-39.0). East Asians were more likely to develop cough (HR: 2.5; 95% CI: 1.1-5.7) and hyperkalaemia (HR: 80.3; 95% CI: 5.4-1190) and African Americans to develop angioedema (HR: 3.5; 95% CI: 1.3-8.9). CONCLUSIONS: Although further validation is necessary, these risk factors should help doctors identify patients with elevated risk for adverse drug events because of ACE inhibitors.     

Abicipar pegol for neovascular age-related macular degeneration

ABSTRACT

Introduction

The development of intravitreal anti-vascular endothelial growth factor (VEGF) therapy has revolutionized management of neovascular age-related macular degeneration (nAMD) and serves as the standard of care for treating this chronic, progressive disease. One shortcoming is the need for frequent intravitreal injections to maintain visual gains, which has led to pursuit of long-acting agents to reduce treatment burden.     

Identification and characterization of [3H]nitrendipine binding sites in rat spinal cord

The present study reports the existence of high-affinity [3H]nitrendipine ([3H]NIT) binding sites in rat spinal cord. Characterization studies revealed [3H]NIT binding to synaptosomes to be specific, rapid and saturable, occurring at a single population of sites. The Bmax was 51 fmol/mg of protein and Kd 0.22 nM with a Hill slope of 0.96. Studies with nifedipine and verapamil demonstrated that the latter binds to a site allosterically linked to the 1,4-dihydropyridine binding sites in spinal cord. The Ca++ channel agonist methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5 carboxylate acted competitively at the 1,4-dihydropyridine binding site and inhibited specific [3H]NIT binding completely. Organic Ca++ antagonists inhibited binding to various degrees. Treatment with EDTA reduced specific [3H]NIT binding in spinal cord by 83%. This was restored by externally added Ca++. The effect of various mono-, di- and trivalent cations on specific [3H]NIT binding as well as its restoration in EDTA-treated preparations was tested. Na+, K+, Li+, Ca++, Mg++, Mn++ and Ba++ were found to have no significant effect. Other cations inhibited binding of [3H]NIT in the sequence La greater than Cd++ greater than Cu++ greater than Co++. Regional studies in rat spinal cord demonstrated 3-fold higher specific [3H]NIT binding sites in the dorsal cord compared to the ventral cord. Moreover, further variations were also found in cervical, thoracic and lumbar regions of the spinal cord. The results demonstrate that binding of the labeled calcium antagonist in spinal cord membranes is of high affinity and completely reversible.(ABSTRACT TRUNCATED AT 250 WORDS)