Translocation between chromosome 5q35 and chromosome 11q13-- an unusual cytogenetic finding in a primary refractory acute myeloid leukemia

Cytogenetic abnormalities are observed in approximately two-thirds of patients with acute myeloid leukemia (AML). Chromosome rearrangements are associated with specific subtypes of AML and associated prognosis. We report a patient with AML, M2, who was primarily refractory to standard induction chemotherapy with idarubicin and cytarabine. Flow cytometry of a bone marrow aspirate showed aberrant expression of B-cell markers including CD19. Cytogenetic studies disclosed a translocation between 5q35 and 11q13. Fluorescence in situ hybridization analyses demonstrated that neither the NSD1 nor MLL genes were involved in this case. Further study is required to define conclusively the genes involved and their contribution to pathogenesis in this case.     

The utility of serial complete blood count monitoring in patients receiving radiation therapy for localized prostate cancer

PURPOSE: It is standard practice in our department to monitor weekly complete blood counts (CBCs) in patients receiving definitive radiation therapy for prostate cancer. The clinical utility and cost effectiveness of this practice has not been analyzed. METHODS AND MATERIALS: The charts of all prostate cancer patients treated with radiation therapy between January 1994 and July 1996 at the Veterans Administration Hospital, Philadelphia, PA were reviewed. CBC values were available for 89 patients. Patients received a median dose of 68 Gy using a four-field box technique and megavoltage photons. Whole-pelvic radiotherapy followed by a conedown to the prostate was administered to 29 patients. Fifty-nine patients received radiation to the prostate alone or prostate and seminal vesicles. Fifty-seven patients received concurrent hormonal therapy which included luteinizing hormone-releasing hormone (LHRH) agonist, antiandrogens, or both. RESULTS: No patient experienced a drop in their hemoglobin, white blood cells (WBCs), or platelets below critical nadirs (defined as WBC < 2 counts x 1000/mm(3), hemoglobin < 8 g/dl, platelet < 50 counts x 1000/mm(3) 2 in WBCs. In the urban area surrounding the Philadelphia Veterans Administration Medical Center, the cost of obtaining a CBC is approximately $30. However, if staff time is considered, the cost of obtaining a weekly CBC during prostate cancer radiotherapy approached $400 per patient. CONCLUSION: These results suggest that weekly monitoring of CBCs in prostate cancer patients undergoing definitive radiotherapy may not be necessary. We recommend a baseline CBC be performed, and if normal, no other monitoring unless clinically indicated. This strategy would result in a cost savings approaching $30,000 per 100 treated patients. Further research on the cost effectiveness and utility of serial blood tests in patients receiving partial body radiation therapy is needed.     

No allele variation of the MAOA gene promoter in male Chinese subjects with attention deficit hyperactivity disorder

The aim of the current study was to examine any difference in the repeat sequence of the monoamine oxidase A (MAOA) gene promoter between males with attention deficit hyperactivity disorder (ADHD) and randomly selected subjects in a community. The role of the MAOA gene promoter in ADHD cases was also investigated. The total of 244 participants included 57 male ADHD subjects as the case group and 187 males, also in southern Taiwan, as the community controls. There was no significantly different distribution in the repeat sequence of the MAOA gene promoter (chi2 = 3.895, d.f. = 3, p = 0.273), and no significantly different distribution of 'long-form' and 'short-form' alleles between the ADHD group and the male community group was noted (chi2 = 2.484, d.f. = 1, p = 0.115). Some aspects of clinical response are mentioned in the discussion of this study which are worth exploring further in the future.     

Expression of E-cadherin, Twist, and p53 and their prognostic value in patients with oral squamous cell carcinoma

Purpose

Epithelial–mesenchymal transition (EMT) and p53 play important roles in controlling cancer invasion and metastasis. However, discrepancies still exist in the relationship between the expression of an epithelial marker E-cadherin and predicting short survival of patients in many types of cancer. In this study, we aimed to determine the levels of E-cadherin, Twist, and p53 in tumor tissues from patients with oral squamous cell carcinoma (OSCC) and their clinical significances.

Methods

The protein expression of 112 OSCC tumor and 16 benign tissues was examined by immunohistochemistry staining. Overall survival rates of 112 OSCC patients were measured using Kaplan–Meier estimates and the log-rank tests.

Results

E-cadherin and p53 downregulation were found in 70 of 112 (62.5 %) and 66 of 112 (59.0 %), respectively, and Twist overexpression was found in 72 of 112 (64.3 %) studied cases of OSCC patients. Expression of E-cadherin was significantly associated with tumor location (P = 0.004) and mortality (P = 0.010). Patients with lower E-cadherin expression (P = 0.024), betel quid chewing (P = 0.006), smoking (P = 0.001), tumor size >2 cm (P = 0.001), advanced tumor stage (P = 0.043), and recurrence (P < 0.001) exhibited a poorer outcome. Multivariate analysis showed that E-cadherin is an independent marker for survival prediction. Additionally, low E-cadherin expression is significantly correlated with low p53 expression.

Conclusions

E-cadherin is an independent marker for survival prediction in OSCC. Co-evaluation of E-cadherin and p53 expression might be a valuable tool for predicting OSCC patient outcome.     

Clinical utility of quantitative HBsAg in natural history and nucleos(t)ide analogue treatment of chronic hepatitis B: new trick of old dog

Using commercial quantitative assays, quantitative hepatitis B surface antigen (qHBsAg) has improved our understanding and management of chronic hepatitis B (CHB). The HBsAg level is highest in the immune tolerance phase, starts to decline during the immune clearance phase, and decreases slowly but progressively after hepatitis B e antigen (HBeAg) seroconversion. The HBsAg level is lowest in individuals with an inactive carrier state but higher in those who develop HBeAg-negative hepatitis. It has been shown that a reduction of HBsAg by 1 log IU/mL or more reflects improved host immune control of HBV infection. A combination of HBsAg <1000 IU/mL and HBV-DNA <2000 IU/mL can identify a 3-year inactive state in a genotype D HBeAg-negative carrier population. In the Asian-Pacific region, where HBV genotypes B and C are dominant, HBsAg levels of ≤10–100 IU/mL predict HBsAg loss over time. As to the prediction of disease progression, low-viremic carriers with HBsAg >1000 IU/mL have been shown to be at higher risks of HBeAg-negative hepatitis, cirrhosis, and hepatocellular carcinoma than those with HBsAg <1000 IU/mL. Although qHBsAg has been widely used in CHB patients receiving pegylated interferon therapy, the HBsAg decline is slow and does not correlate with HBV-DNA levels during nucleos(t)ide analogue (NUC) therapy. However, a rapid HBsAg decline during NUC therapy may identify patients who will finally clear HBsAg. A 6- to 12-monthly assessment of HBsAg level could be considered during NUC therapy. Taking these lines of evidence together, qHBsAg can complement HBV-DNA levels to optimize the management of CHB patients in our daily clinical practice.     

Association between the characteristics of metabolic syndrome and Alzheimer’s disease

Various epidemiological studies have shown that type 2 diabetes and metabolic syndrome are highly correlated with Alzheimer’s disease (AD). Here, we sought to assess the impact of metabolic syndrome characteristics on the progression of AD. Five-week-old male, spontaneously hypertensive (n?=?32) and Wistar Kyoto (abbreviated WKY; n?=?8) rats were divided into 5 groups (each n?=?8): WKY, hypertension (HTN), streptozotocin-induced diabetes (STZ), high-fat diet (HFD), and STZ + high-fat diet-induced diabetes mellitus (DM). All animals were sacrificed and samples of the blood, liver, and brain were collected for further biological analysis. During the 15-week period of induction, the STZ and DM groups (animals injected with low-dose STZ) had significantly higher fasting glucose levels; the HFD group had elevated insulin levels, but normal blood glucose levels. The HFD and DM groups had hypercholesterolemia and higher hepatic levels of triglycerides and cholesterol. Additionally, correlations between HFD and elevated brain amyloid-beta 42 (Aβ-42), hyperglycemia and down-regulation of brain insulin receptor, and serum Aβ-42 and hepatic triglyceride concentrations (r²?=?0.41, p?<?0.05) were observed. Serum C-reactive protein and malondialdehyde did not appear to have a significant influence on the association with biomarkers of AD. Thus, our study demonstrated that rats with characteristics of metabolic syndrome had a large number of biomarkers predicting AD; however, no relationship between traditional inflammatory and oxidative markers and AD was found. Further studies are necessary to prove that these findings in rats are relevant to AD processes in humans.     

Asparagine Deamidation Dependence on Buffer Type,pH, and Temperature

The deamidation of asparagine into aspartate and isoaspartate moieties is a major pathway for the chemical degradation of monoclonal antibodies (mAbs). It can affect the shelf life of a therapeutic antibody that is not formulated or stored appropriately. A new approach to detect deamidation using ion exchange chromatography was developed that separates papain-digested mAbs into Fc and Fab fragments. From this, deamidation rates of each fragment can be calculated. To generate kinetic parameters useful in setting shelf life, buffers prepared at room temperature and then placed at the appropriate stability temperatures. Solution pH was not adjusted to the same at different temperatures. Deamidation rate at 40°C was faster in acidic buffers than in basic buffers. However, this trend is reversed at 5°C, attributed to the change in hydroxide ion concentration influenced by buffer and temperature. The apparent activation energy was higher for rates generated in an acidic buffer than in a basic buffer. The rate-pH profile for mAbl can be deconvoluted to Fc and Fab. The Fc deamidation showed a V-shaped profile: deamidation of PENNY peptide is responsible for the rate at high-pH, whereas deamidation of a new site, Asn323, may be responsible for the rate at low-pH. The profile for Fab is a straight line without curvature.     

Biomechanical and histological studies of particulate hydroxylapatite implanted in femur bone defects of adult dogs

The purpose of this study was to investigate the biomechanical behavior and the histology of particulate hydroxylapatite (HA) implanted in bone defects created in femurs of 48 adult mongrel dogs. The bone defects, measuring 10 x 10 x 25 mm with or without HA implantation, were allowed to heal until the end of the 1st, 2nd, 3rd, 6th, 9th and 12th months after surgery. The harvested tissue specimens from the implant sites were processed into long cubic or rectangular prismatic forms. Their mechanical strengths were assessed using compression and shearing tests to measure the maximal compressive and shear stress by force loading on the middle portions of the specimens. Histological sections of each stage were processed with both decalcified and nondecalcified methods. The results showed that the mechanical strength of the tested specimens was closely related to the tissue regeneration within the bone defect. Progressive regeneration of new bone was observed at each stage, with complete bone formation at the 9-month period. A consistent increase in both maximal compressive stress and maximal shear stress was noted at each stage, responsive to the ossification and maturation of the regenerating tissue within the bone defect. This animal model provides a novel approach to directly estimate the tissue strength of the HA-implanted bone defect.     

Factors influencing discomfort during anterior ultrasound-guided injection for hip arthrography

BackgroundAlthough ultrasound (US)-guided injection techniques for magnetic resonance arthrography of the hip have been used with increasing frequency to diagnose internal joint derangements, little is known about patient tolerance, which is relevant information for patients. The objective of this study was to evaluate prospectively the association between possible influencing factors and discomfort felt during the performance of anterior US-guided injection techniques targeting the femoral head–neck junction during hip arthrography.MethodsForty-four consecutive patients (21 women and 23 men; mean age, 41 years) undergoing magnetic resonance hip arthrography were sequentially assigned to receive injection alternating between fixed and freehand US-guided injection. Discomfort was assessed using a visual analog scale and relative ratings. Patient body mass index, extra-articular contrast leakage, the duration of the procedure, the needle advancement distance, and the fixed trajectory of the needle were assessed. Pearson’s correlation coefficients and multiple logistic regression analysis were used to determine the association.ResultsPuncture was successfully accomplished in all cases, and no relevant complications were reported. The only significant relationships were between discomfort and the time required for needle manipulation (r = 0.8) and fixed US-guided injection (r = 0.6; p < 0.001). Compared with the freehand technique, the fixed technique resulted in significantly less pain and took significantly less time to perform (p < 0.001). The procedure time during needle manipulation in the fixed US-guided injections (4.0 ± 0.9 seconds) was significantly less than that in the freehand US-guided injections (19.4 ± 17.6 seconds; p < 0.001). No significant relationships were found between discomfort and other parameters (r < 0.3, p > 0.05).ConclusionThe procedure time appears to be the most important factor influencing patient discomfort. Fixed US-guided injection is a time-saving technique that alleviates procedure-related discomfort.