Clonal evolution of t(14;18) follicular lymphomas demonstrated by immunoglobulin genes and the 18q21 major breakpoint region

A 2.8-kilobase major breakpoint region on chromosome segment 18q21 is the site of most t(14;18) translocations typical of human follicular lymphomas. Breaks are focused at the 5' end of joining (JH) regions of immunoglobulin (Ig) on chromosome 14, indicating that the translocation occurs at a pre-B-cell stage during attempted heavy (H) chain joining. A new gene from 18q21 (Bcl-2) is placed in the H chain locus creating a unique, translocation-specific JH;18q21 rearrangement that presumably represents a transformation event. In addition, normal Ig gene joining occurs in a H before light (L) chain and K before lambda cascade, creating ordered clonal markers. These serial markers were examined to determine if variations in Ig gene patterns during the natural history of lymphomas represent the emergence of truly separate neoplasms or heterogeneity of a single neoplasm. We examined 45 serial biopsies from 16 B follicular lymphoma patients; six cases showed variation in Ig gene patterns over time. Seven individuals had a detectable JH;18q21 rearrangement present, and it remained unchanged over 5-10 years. Further rearrangements of H chain genes occurred on the normal chromosome 14 within evolving subclones of the original tumor. Lambda L chains also underwent additional rearrangements in two instances, while K gene patterns remained unchanged. All variations in the normal H and L chain genes were 2 degrees rearrangements occurring at a mature B-cell stage following the initial successful rearrangement of a H and L chain. In contrast the t(14;18) breakpoint was conserved in each individual, indicating that evolving neoplastic subpopulations arose from a common clonal progenitor cell.     

Gene rearrangements as markers of clonal variation and minimal residual disease in acute lymphoblastic leukemia

Immunoglobulin (Ig) heavy (H) and light (L) chain gene rearrangements were used as molecular markers of clonal evolution and minimal residual disease in B cell precursor acute lymphoblastic leukemia (ALL). All leukemic episodes within individual patients shared at least one identical Ig rearrangement and thus arose from a common clonal progenitor cell. Nine of 11 patients displayed completely identical patterns between leukemic episodes, while two of 11 patients demonstrated genetic progression between diagnosis and relapse as evidenced by additional rearrangements. These genetic changes marked the emergence of leukemic subclones. Ig gene rearrangements were also used as sensitive markers to identify clonal cell populations in ALL patients following induction or reinduction therapy and to search for residual bone marrow disease in patients in clinical remission or with isolated extramedullary relapse. DNA rearrangements provide tumor-specific markers to follow the genetic variation of ALL and may facilitate the early detection of recurrent disease.     

Serologic examinations of hepatitis,cytomegalovirus, and rubella in patients with Bell's palsy

OBJECTIVE: The aim of this retrospective case review was to investigate serologic evidence of cytomegalovirus, rubella virus, and hepatitis A, B, and C viruses in patients with Bell's palsy. DESIGN: A total of 24 patients with idiopathic facial paralysis, without a history of trauma, any evidence of a tumor on high-resolution computed tomographic imaging, or any otologic disease, and 33 healthy individuals as a control group were included in this study. Facial paralysis of the patient was evaluated with the House-Brackmann grading scale. Specific immunoglobulin G and M titers were determined for cytomegalovirus, rubella, hepatitis A, hepatitis B, and hepatitis C by enzyme-linked immunosorbent assay. RESULTS: Serologic positivity for hepatitis B was found in 15 of 21 Bell's palsy patients, compared with 32.1% in the control group. The difference was statistically significant. There was no difference in the prevalence of serologic positivity for cytomegalovirus, hepatitis A, and rubella between the patient and control groups. In one Bell's palsy patient, serologic evidence of recent cytomegalovirus infection was indicated by changes in antibody titers between samples taken on presentation and on the 16th day. There was no serologic evidence of hepatitis C in either Bell's palsy patients or the control group. CONCLUSION: There seems to be an association between hepatitis B and idiopathic facial paralysis. In addition, cytomegalovirus might contribute to the development of Bell's palsy in some ceases with Bell's palsy. Further studies are required to confirm these data.     

The assessment of normal early pregnancy by transvaginal color Doppler ultrasonography

Transvaginal color Doppler was performed in 198 volunteer pregnant women whose menstrual age ranged from the fifth to the twelfth week. In all patients an attempt was made to obtain signals from both uterine arteries, peritrophoblastic/retroplacental vessels, umbilical arteries, fetal aorta, intracranial vessels, and corpus luteum flow. With the combination of color and pulsed Doppler transvaginal sonography, detection of vascular structures was greatly facilitated and the amount of time for examination significantly reduced. Flow velocity waveforms were measured and results were analyzed by calculation of the Resistance Index. During the early stage of pregnancy, we were able to locate both uterine arteries in all cases and continuous diastolic shift signal was found. Flow in the peritrophoblastic/retroplacental area was observed with an overall success rate of 94%. Blood flow in the umbilical artery and fetal aorta was visualized by color Doppler starting from the seventh week. Intracranial blood flow could be visualized starting from the tenth week in some cases. Diastolic flow in these vessels was detectable starting from the twelfth week. Corpus luteum flow was found in 148 cases (75%) and the Resistance Index decreased as pregnancy progressed © 1993 by John Wiley & Sons, Inc.     

Comparison of demographic and clinical characteristics of hospitalized COVID-19 patients with severe/critical illness in the first wave versus the second wave

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65–157) vs. 87 mg/L (IQR: 39–140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.     

A double-blind,crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy

Background Granisetron is a safe and effective prophylaxis for nausea and vomiting associated with moderate to highly emetogenic chemotherapy. Few trials have been conducted to determine the optimal effective dose of granisetron in children with cancer. The objective of this report was to compare two doses of granisetron in patients with optic pathway tumors receiving moderately emetogenic doses of carboplatin. Patients and methods In this double-blind, crossover, randomized study, antiemetic efficacy and tolerability of two dose levels (10 and 40 μg/kg) of granisetron in the prevention of acute and delayed nausea/emesis were compared in children and young adults. A total of 18 patients (13 boys) aged 1–23 years (median 7.7 years) treated with a moderately emetogenic dose of carboplatin were randomly assigned to receive either 10 or 40 μg/kg of slow granisetron intravenous (i.v.) infusions at alternating cycles of chemotherapy in a blinded fashion until the end of the study period or until their chemotherapy regimen ended. In this way, the patients acted as their own controls. Results Patients in the granisetron 10 and 40 μg/kg groups received 104 and 121 cycles of chemotherapy, respectively. There was no significant difference in antiemetic efficacy in terms of nausea and emesis between the dose groups in the first 5 days of chemotherapy. The treatment was well tolerated. Conclusion We conclude that granisetron 10 and 40 μg/kg have comparable efficacy in controlling carboplatin-induced acute and delayed nausea/emesis and is well tolerated in children and young adults.     

Comparison of antioxidant activity in commercial Ginkgo biloba preparations

AIM: To compare the relative levels of antioxidant activity in vitro in Ginkgo biloba samples (in tablet or capsule form) from different commercial suppliers, to determine whether some brands may be more efficacious in their potential to increase endogenous antioxidant activity, and thereby counter oxidative stress related disorders. DESIGN: Antioxidant activity of the above sample extracts was determined in vitro against the ABTS.(+) (2-2'-amino-bis-3-ethylbenzthiazoline-6-sulfonic acid) radical, relative to Trolox (water-soluble vitamin E analogue) antioxidant standards, using an established assay procedure. OUTCOME MEASURES: The relative antioxidant activity of G. biloba sample extracts was expressed in terms of millimoles per liter of Trolox equivalent (TE) for the initial extract, micromol TE per whole tablet, nmol TE per mg tablet, and nmol TE per mg ginkgo content. RESULTS: Data (as mean +/- standard deviation (SD) from 4 separate estimations) obtained in this study showed a considerable variation (approximately 50-fold) in the level of antioxidant activity in preparations from different suppliers, particularly when compared on an equivalent (i.e., nmol TE/mg ginkgo) basis. Of the 18 products investigated, the highest level of antioxidant activity (whether expressed as micromol TE per whole tablet or nmol TE/mg ginkgo) was obtained for Pharma Nord Bio-Biloba (Pharma Nord, Morpeth, UK) tablets (p < 0.05, Dunnett's statistical test). CONCLUSIONS: Some of the apparent variation in antioxidant activity of the various products investigated can be accounted for in terms of the physical nature of the G. biloba (i.e., dried leaf powder or standardized concentrated extract) used in tablet formulation. However, even when comparing products based on concentrated extract, the data demonstrated that there is still a considerable variation in antioxidant activity. Presumably this may result from differences in the manufacturing process between suppliers, which in turn may limit the efficacy of these preparations in the prevention or treatment of disease.