Monocytoid B-cell lymphoma: its evolution and relationship to other low- grade B-cell neoplasms

Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.     

Technetium-99m sestamibi myocardial imaging at rest for assessment of myocardial infarction and first-pass ejection fraction. Multicenter Cardiolite Study Group.

The ability of technetium (Tc)-99m sestamibi myocardial perfusion imaging at rest to evaluate myocardial infarction and first-pass ejection fraction was studied in a trial involving 18 institutions. Protocol I compared regional perfusion with occurrence of infarction by Q wave or by gated blood pool scan wall motion abnormality in 146 patients. Protocol II assessed first-pass right and left ventricular ejection fraction in 85 patients. In protocol I, Tc-99m sestamibi images were abnormal in 104 of 111 patients (94%) with both a Q wave and a gated scan wall motion abnormality and was normal in 23 of 25 patients (92%) in whom both were normal. Therefore, concordance existed in 105 (94%) patients. Of 115 patients with a Q wave, 107 (93%) had an abnormal Tc-99m sestamibi study. Of 115 patients with a gated scan wall motion abnormality, 108 (94%) had an abnormal Tc-99m sestamibi study. Tc-99m sestamibi imaging showed corresponding perfusion abnormalities in 81% of 69 anterior Q-wave infarcts, 73% of 55 inferior Q-wave infarcts and 88% of 8 posterior infarcts. Specificity in normal regions on electrocardiography and wall motion was 91, 100 and 100%, respectively, for anterior, inferior and posterior regions, respectively, between wall motion and perfusion. Of 17 myocardial segments per patient, there was concordance in 74% of patients. First pass Tc-99m sestamibi imaging of ejection fraction agreed well with conventional first-pass imaging for the right and left ventricle. It is concluded that Tc-99m sestamibi myocardial imaging at rest reliably diagnoses and localizes infarction and assesses ejection fraction by first-pass imaging.     

Rapid diagnosis of spontaneous bacterial peritonitis with leukocyte esterase reagent strips in a European and in an American center

BACKGROUND: Timely diagnosis and treatment of spontaneous bacterial peritonitis (SBP) are essential to survival. The purpose of the present paper was to evaluate leukocyte esterase reagent strips (Nephur-Test and MultistixSG10) in the bedside diagnosis of SBP. METHODS: Patients with cirrhotic ascites were prospectively included in France (center 1) and in the USA (center 2). Paracenteses were performed on admission and repeated as indicated. Bedside reagent strip testing was performed on the ascitic fluid and compared to manual cell count with differential and ascitic fluid culture. In center 1, the Nephur-Test was tested in all cases, with dual testing with MultistixSG10 in a subgroup. In center 2, all cases had dual testing. Spontaneous bacterial peritonitis was defined as a polymorphonuclear ascites count > or =250/microL. RESULTS: A total of 184 samples was obtained in 76 patients. Center 1 included 151 samples from 53 patients. Seven samples had SBP, obtained in six patients. Center 2 included 33 samples from 23 patients. Six samples had SBP, obtained in five patients. The sensitivity, specificity, positive and negative predictive value of the reagent strips were as follows. Center 1/Nephur-Test: 86%, 100%, 100%, 99%; center 1/MultistixSG10: 100%, 100%, 100%, 100%; center 2/Nephur-Test: 100%, 92.5%, 75%, 100%; center 2/MultistixSG10: 83%, 96%, 83%, 96%. CONCLUSION: Leukocyte esterase reagent strips may provide a rapid bedside diagnosis of SBP.     

Average spectral power changes at the hippocampal electroencephalogram in schizophrenia model induced by ketamine

The use of ketamine (Ket) as a pharmacological model of schizophrenia is an important tool for understanding the main mechanisms of glutamatergic regulated neural oscillations. Thus, the aim of the current study was to evaluate Ket‐induced changes in the average spectral power using the hippocampal quantitative electroencephalography (QEEG). To this end, male Wistar rats were submitted to a stereotactic surgery for the implantation of an electrode in the right hippocampus. After three days, the animals were divided into four groups that were treated for 10 consecutive days with Ket (10, 50, or 100 mg/kg). Brainwaves were captured on the 1st or 10th day, respectively, to acute or repeated treatments. The administration of Ket (10, 50, or 100 mg/kg), compared with controls, induced changes in the hippocampal average spectral power of delta, theta, alpha, gamma low or high waves, after acute or repeated treatments. Therefore, based on the alterations in the average spectral power of hippocampal waves induced by Ket, our findings might provide a basis for the use of hippocampal QEEG in animal models of schizophrenia.     

Adherence to Daily Oral TDF/FTC for PrEP in Community Health Center Populations: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Study

AIDS and Behavior - The prevention effectiveness of oral preexposure prophylaxis (PrEP) is highly dependent on medication adherence but no validated longer term PrEP adherence measures are readily...     

Colonic motility and transit in health and ulcerative colitis

Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.     

Targeting NF-kappaB in Waldenstrom macroglobulinemia

The nuclear factor-B (NF-B) path-way has been implicated in tumor B-cell survival, growth, and resistance to therapy. Because tumor cells overcome single-agent antitumor activity, we hypothesized that combination of agents that target differentially NF-B pathway will induce significant cytotoxicity. Therapeutic agents that target proteasome and Akt pathways should induce significant activity in B-cell malignancies as both pathways impact NF-B activity. We demonstrated that perifosine and bortezomib both targeted NF-B through its recruitment to the promoter of its target gene IB using chromatin immunoprecipitation assay. This combination led to synergistic cytotoxicity in Waldenstrom macroglobulinemia (WM) cells that was mediated through a combined reduction of the PI3K/Akt and ERK signaling pathways, found to be critical for survival of WM cells. Moreover, a combination of these drugs with the CD20 monoclonal antibody rituximab further increased their cytotoxic activity. Thus, effective WM therapy may require combination regimens targeting the NF-B pathway.      

Mammary gland sympathetic innervation is a major component in type 1 deiodinase regulation

Recent observations have shown that in lactating rats previously deprived of suckling, either suckling stimulus or ip injection of norepinephrine was capable of increasing mammary deiodinase type 1 (M-D1) mRNA content and enzyme activity. In the present work, we show that intact efferent sympathetic mammary innervation is required to restore both mammary D1 mRNA content and enzyme activity, whereas suckling-induced secretion of catecholamines from the adrenal glands does not seem to participate in M-D1 enzyme regulation. The data also indicate that the sympathetic reflex activation in response to suckling involves two complementary autonomic components: (1) activation, presumably through mammary segmental arrangement affecting neighboring mammary glands; and (2) an individual reflex regulatory mechanism capable of maintaining M-D1 activity within each mammary gland. In addition to these findings, we show that the suckling-induced sympathetic activation of M-D1 activity could be blocked by prior activation of ductal mechanoreceptors. This set of regulatory and counterregulatory mechanisms seems to ensure the optimal control of mammary energetic expenditure according to litter size.     

Prognostic Implications of Restrictive Left Ventricular Filling in Acute Myocardial Infarction: A Serial Doppler Echocardiographic Study

Objectives. This study was designed to evaluate the relative prognostic significance of restrictive left ventricular (LV) filling after acute myocardial infarction.

Background. Data regarding the contribution of diastolic dysfunction to prognosis after myocardial infarction are limited, and the additional value over the assessment of systolic dysfunction is not known.

Methods. Serial Doppler echocardiography was performed in 95 patients on days 1, 3 and 7 and 3 months after acute myocardial infarction. Patients were classified into two groups: a restrictive group (n = 12) with a peak velocity of early diastolic filling wave (E)/peak velocity of late filling wave (A) ratio ≥2 or between 1 and 2 and a deceleration time (DT) ≤140 ms during at least one echocardiographic study; and a nonrestrictive group (n = 83) with an E/A ratio ≤1 or between 1 and 2 and a DT >140 ms at all examinations.

Results. Cardiac death occurred in 10 patients during a mean follow-up interval of 32 ± 17 months. The survival rate at 1 year was 100% in the nonrestrictive group and only 50% in the restrictive group. After 1 year there was a continuing divergence of mortality, resulting in a 3-year survival rate of 100% and 22%, respectively. Univariate Cox analysis revealed that restrictive LV filling, wall motion score index, ejection fraction and end-systolic and end-diastolic volume indexes, as well as peak creatine kinase, peak MB fraction and heart failure during the hospital course were significant predictors of cardiac death, although restrictive filling was the single best predictor (p < 0.0001). Multivariate analysis showed that restrictive filling adds prognostic information to clinical and echocardiographic variables of systolic dysfunction.

Conclusions. Restrictive LV filling after acute myocardial infarction is the single best predictor of cardiac death and adds significantly to clinical and echocardiographic markers of systolic dysfunction.