Immunophenotypic features by multiparameter flow cytometry can help distinguish low grade B‐cell lymphomas with plasmacytic differentiation from plasma cell proliferative disorders with an unrelated clonal B‐cell process

Highly sensitive flow cytometry studies may incidentally identify B cell clones when used to assess plasma cell clonality in bone marrows. Clinical history, which can help differentiate related clones (low grade B cell lymphoma with plasmacytic differentiation/LBCL‐PD) from unrelated ones (plasma cell proliferative disorder (PCPD) with an unrelated B cell clone), is often unavailable in referred specimens. We sought to identify morphologic or phenotypic features that would help predict the significance of these clones in the absence of history. We included only cases with identical light chain B and plasma cell clones, as determined by 6‐color flow cytometry with additional DNA ploidy analysis, in which the relationship between clones could be established by review of medical records. There were 26 cases; 18 were related (14 were Waldenstrom macroglobulinemia) and eight were unrelated (seven multiple myeloma). Features seen exclusively in LBCL‐PD include CD19+/CD45+ clonal plasma cell phenotype (66·7%, P = 0·0022) and morphologic features such as paratrabecular bone marrow involvement, increased mast cells, and plasma cells surrounding B‐cell nodules. Aneuploidy was identified exclusively in PCPD cases (75%, P = 0·000028). We conclude that CD19+/CD45+ clonal plasma cell phenotype and aneuploidy are useful in distinguishing related clones (LBCL‐PD) from unrelated clones (PCPD).     

Ischemia-reperfusion model in rat spinal cord: cell viability and apoptosis signaling study

This work aimed at determining the ideal ischemia time in an in vitro ischemia-reperfusion model of spinal cord injury. Rat spinal cord slices were prepared and then exposed or not to oxygen deprivation and low glucose (ODLG) for 30, 45, 60, 75 and 90 minutes. Cell viability was assessed by triphenyltetrazolium (TTC), lactate dehydrogenase (LDH) release, and fluorochrome dyes specific for cell dead (ethidium homodimer) using the apotome system. Glutamate release was enzymatically measured by a fluorescent method. Gene expression of apoptotic factors was assessed by real time RT-PCR. Whereas spinal cord slices exposed to ODLG exhibited mild increase in fluorescence for 30 minutes after the insult, the 45, 60, 75 and 90 minutes caused a 2-fold increase. ODLG exposure for 45, 60, 75 or 90 minutes, glutamate and LDH release were significantly elevated. nNOS mRNA expression was overexpressed for 45 minutes and moderately increased for 60 minutes in ODLG groups. Bax/bcl-xl ratio, caspase 9 and caspase 3 mRNA expressions were significantly increased for 45 minutes of ODLG, but not for 30, 60, 75 and 90 minutes. Results showed that cell viability reduction in the spinal cord was dependent on ischemic time, resulting in glutamate and LDH release. ODLG for 45 minutes was adequate for gene expression evaluation of proteins and proteases involved in apoptosis pathways.     

The Relationship Between Nocturnal Blood Pressure and Hemorrhagic Stroke in Chinese Hypertensive Patients

To study the relationship between nocturnal blood pressure (BP) variation and spontaneous intracerebral hemorrhage (ICH) among Chinese hypertensive patients and its clinical significance, the authors retrospectively screened 371 patients with primary hypertension (189 patients with ICH, 182 patients without ICH) in Shanghai and analyzed their demographics, clinical information, nocturnal blood pressure variability and medication. Compared with the control group, the levels of blood glucose, triglycerides, and creatinine were significantly increased in the ICH group, along with a marked reduction in nocturnal BP drop (P<.05). Multivariate logistic regression indicated that blood glucose, creatinine, and nocturnal mean arterial pressure were risk factors for ICH, and the magnitude of nocturnal BP drop was negatively related to the risk for ICH. There was no significant difference in the prevalence of reverse dippers between the large hematoma volume group and the small hematoma volume group (χ²=2.529, P=.112), nor among the patients taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers (χ²=1.981, P=.371). Reverse dipping is associated with the risk for ICH, suggesting that appropriate antihypertensive drug and chronotherapy might be effective to normalize the rhythm of abnormal circadian variation in hypertensive patients.     

Elevated Serum Uric Acid is Associated With Angiotensinogen in Obese Patients With Untreated Hypertension

This study investigated the correlation between elevated serum uric acid (SUA) and angiotensinogen in obesity patients with hypertension. A total of 162 obese and 162 nonobese men with hypertension were recruited in this study. Plasma angiotensinogen levels were measured by enzyme‐linked immunosorbent assay. Fasting insulin (FINS) was evaluated by radioimmunoassay. Compared with nonobese patients, obese patients exhibited higher levels of angiotensinogen, FINS, and homeostasis model assessment index‐insulin resistance (HOMA‐IR) (P<.001 for all). Moreover, these indexes significantly increased in obese patients in the highest tertile of SUA when compared with those in the lowest tertile of SUA (P<.001, P=.002, P=.007, respectively). In the obese group, SUA levels were significantly related to angiotensinogen, FINS, and HOMA‐IR, respectively. Furthermore, it was demonstrated that obesity × uric acid was an independent contributor to angiotensinogen (β=0.257, P<.001). In conclusion, elevated SUA is strongly related to angiotensinogen in an obesity‐dependent manner in hypertension.     

Calcium Channel Blocker Compared With Angiotensin Receptor Blocker for Patients With Hypertension: A Meta‐Analysis of Randomized Controlled Trials

To explore the clinical effects of a calcium channel blocker compared with an angiotensin II receptor blocker in hypertensive patients, the authors collected data from randomized controlled trials. The pooled outcomes were all‐cause mortality, stroke, myocardial infarction, and heart failure. Eight head‐to‐head trials enrolling 25,084 patients were included. There was no significant mortality difference in the two arms (relative risk, 0.99; 95% confidence interval, 0.91–1.07). However, calcium channel blockers were more effective in reducing stroke (relative risk, 0.87; 95% confidence interval, 0.76–0.99) and myocardial infarction incidence (relative risk, 0.86; 95% confidence interval, 0.76–0.98). There was no significant difference with heart failure incidence between the two arms but a lower trend in patients with angiotensin II receptor blockers was noted (relative risk, 1.4; 95% confidence interval, 0.99–1.98). The meta‐analysis suggested that initially use of a calcium channel blocker might be superior to an angiotensin II receptor blocker for prevention of stroke and myocardial infarction.     

Genetic diversity of 3′ region of glycoprotein D gene of bovine herpesvirus 1 and 5

Bovine herpesviruses 1 (BoHV-1) and 5 (BoHV-5) are closely related alphaherpesviruses of cattle. While BoHV-1 is mainly associated with respiratory/genital disease and rarely associated with neurological disease, BoHV-5 is the primary agent of meningoencephalitis in cattle. The envelope glycoprotein D of alphaherpesviruses (BoHV-1/gD1 and BoHV-5/gD5) is involved in the early steps of virus infection and may influence virus tropism and neuropathogenesis. This study performed a sequence analysis of the 3′ region of gD gene (gD3′) of BoHV-1 isolates recovered from respiratory/genital disease (n = 6 and reference strain Cooper) or from neurological disease (n = 7); and from seven typical neurological BoHV-5 isolates. After PCR amplification, nucleotide (nt) sequencing, and aminoacid (aa) sequence prediction; gD3′ sequences were compared, identity levels were calculated, and selective pressure was analyzed. The phylogenetic reconstruction based on nt and aa sequences allowed for a clear differentiation of BoHV-1 (n = 14) and BoHV-5 (n = 7) clusters. The seven BoHV-1 isolates from neurological disease are grouped within the BoHV-1 branch. A consistent alignment of 346 nt revealed a high similarity within each viral species (gD1 = 98.3 % nt and aa; gD5 = 97.8 % nt and 85.8 % aa) and an expected lower similarity between gD1 and gD5 (73.7 and 64.1 %, nt and aa, respectively). The analysis of molecular evolution revealed an average negative selection at gD3′. Thus, the phylogeny and similarity levels allowed for differentiation of BoHV-1 and BoHV-5 species, but not further division in subspecies. Sequence analysis did not allow for the identification of genetic differences in gD3′ potentially associated with the respective clinical/pathological phenotypes, yet revealed a lower level of gD3′ conservation than previously reported.