The Middle-East connection of Wolman Disease

The clinical, laboratory and cytological features of 2 Bahraini infants with Wolman's disease are described. While one of the cases showed the classical diagnostic features, the other case exhibited a few atypical features such as lack of adrenal calcification and unusual morphology of vacuolated marrow macrophages. Literature review shows that this disorder may not be rare in this region.     

Near-haploid acute lymphoblastic leukemia: a unique subgroup with a poor prognosis?

We describe two adolescent girls with acute lymphoblastic leukemia (ALL) whose leukemia cells were near-haploid. Their lymphoblasts stained in a block pattern with periodic acid Schiff and had "common ALL" surface markers confirmed by indirect immunofluorescence. Each patient had two populations of blasts, one near-haploid and one hyperdiploid, which was an exact doubling of the near-haploid karyotype. The first patient had a predominant population of cells with 26 chromosomes and a few with 52, while the second had a predominance of cells with 56 and a minority with 28. Flow cytometric analysis of DNA content initially detected the minor near-haploid population in the second patient, which was confirmed later by cytogenetic review of the marrow sample. In addition to our two patients, only four patients have been reported with near-haploid ALL. Of these six, five were girls, five were adolescents, and five had short survivals (median, 10 mo). All six had disomy of chromosome 21 with or without disomy for chromosomes 10, 14, 18, or X (four patients each). Thus, near-haploid ALL may represent a unique subgroup of ALL with a poor prognosis. To detect these and other possible subgroups, we have included cytogenetic analysis and flow cytometric analysis of DNA content in our initial evaluation of patients with ALL.     

A novel treatment of childhood lymphoblastic non-Hodgkin's lymphoma: early and intermittent use of teniposide plus cytarabine

We treated 24 children and adolescents with stage III or IV lymphoblastic non-Hodgkin's lymphoma, using a protocol designed for patients with poor-prognosis acute lymphoblastic leukemia (ALL). Early therapy consisted of teniposide plus cytarabine administered before and immediately after prednisone, vincristine, and asparaginase. The two- drug combination was also given intermittently with continuous 6- mercaptopurine and methotrexate during the first year of continuation chemotherapy. Periodic intrathecal methotrexate and delayed cranial irradiation were used to prevent central nervous system involvement. Anthracycline compounds, alkylating agents, high-dose methotrexate, and involved-field irradiation were not used in any phase of treatment. Twenty-two (96%) of the 23 evaluable patients achieved complete remission. With a median follow-up of 2 1/2 years, only four patients have relapsed; the remainder have been disease-free for eight months to more than five years. The projected four-year continuous complete remission rate is 73% for all patients and 79% for the 19 with mediastinal involvement at diagnosis. These results demonstrate that use of teniposide plus cytarabine with an otherwise conventional plan of ALL therapy is an effective approach to the treatment of childhood lymphoblastic lymphoma.     

Bcl-2 family member Mcl-1 expression is reduced under hypoxia by the E3 ligase FBW7 contributing to BNIP3 induced cell death in glioma cells

Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over-expressed in the malignant brain tumor glioblastoma (GBM). It has been previously shown that epidermal growth factor receptors up-regulate Mcl-1 contributing to a cell survival response. Hypoxia is a poor prognostic marker in glioblastoma despite the fact that hypoxic regions have areas of necrosis. Hypoxic regions of GBM also highly express the pro-cell death Bcl-2 family member BNIP3, yet when BNIP3 is overexpressed in glioma cells, it induces cell death. The reasons for this discrepancy are unclear. Herein we have found that Mcl-1 expression is reduced under hypoxia due to degradation by the E3 ligase FBW7 leading to increased hypoxia induced cell death. This cell death is reduced by EGFR activation leading to increased Mcl-1 expression under hypoxia. Conversely, BNIP3 is over-expressed in hypoxia at times when Mcl-1 expression is decreased. Knocking down BNIP3 expression reduces hypoxia cell death and Mcl-1 expression effectively blocks BNIP3 induced cell death. Of significance, BNIP3 and Mcl-1 are co-localized under hypoxia in glioma cells. These results suggest that Mcl-1 can block the ability of BNIP3 to induce cell death under hypoxia in GBM tumors.     

Acute clinical evaluation of a left ventricular automatic threshold determination algorithm based on evoked response sensing

Introduction: Automatic pacing threshold (AT) testing may simplify device follow‐up and improve device longevity. This study's objective was to evaluate the performance of a left ventricular (LV) evoked response sensing‐based AT algorithm, for cardiac resynchronization therapy (CRT) devices. Methods: Patients scheduled for CRT‐D/P implant were enrolled. A manual step‐down threshold test and a Left Ventricular Automatic Threshold (LVAT) test in each of four pacing vectors—LVTip→Can, LVTip→right ventricle (RV), = LVRing→Can, and LVRing→RV—were conducted. Patients were randomized to either 0.4‐ms or 1.0‐ms pacing pulse width and in the manual and LVAT test order. A blinded core lab electrophysiologist (EP) determined the threshold using the surface electrocardiogram (gold standard). Results: Data from 70 patients were analyzed. Bipolar LV leads from three major manufacturers were used. A total of 273 AT tests were performed; 12 AT tests did not result in a threshold due to improper testing conditions. Of 261 eligible tests, 234 AT tests (89.6%) returned a threshold measurement. Of the 234 tests, in 233 tests (99.5%) the algorithm‐determined threshold matched the EP‐determined threshold for that test. A total of 16,689 capture and 526 noncapture beats were collected and the accuracy for detecting capture and noncapture were 98.5% and 99.7% with a two‐sided 95% confidence level of (98.4%, 98.7%) and (99.4%, 100%), respectively. No AT threshold measurement was lower than the EP‐determined threshold. Conclusion: In this study, the results suggest that the LVAT algorithm is accurate at determining pacing thresholds in multiple pacing configurations and a wide range of LV leads in CRT‐D/P patients. (PACE 2011;1–5)     

An overview on antidiabetic medicinal plants having insulin mimetic property

Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world''s population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.     

A study on BMI among the Bhotia of Uttaranchal,India

ObjectiveTo investigate the nutritional status of the males and females in two subgroups of the Bhotia tribe (Marcha and Tolcha) inhabiting in three different altitudes in Uttaranchal, India.MethodsData were collected from the Tolcha and Marcha, two sub-groups of the Bhotia, inhabiting in Chamoli district of Uttaranchal. Bhotia adults of both sexes were considered. Field investigation was conducted in three ecological zones (high, middle and low altitude) of the district during April-August, in the years 2002-2004. Anthropometric measurements were obtained in accordance with the techniques recommended by Weiner and Lourie (1981). The variables like height, weight, waist circumference, hip circumference, waist-hip ratio and blood pressure were studied in relation to BMI.ResultsRelatively higher value of mean BMI is recorded among the females than that of the males, which is true for different altitudes, in both subgroups. The BMI also indicates an inverse relationship with altitude, except for the Tolcha males in high altitude. Lowest mean BMI is recorded in middle altitude among the Tolcha subgroup. Chronic energy deficient (CED) individuals are much more than twice the number among the males of both the subgroups inhabiting in different altitudes. Interestingly, the percentage of CED individuals increases with the altitude.ConclusionsRegression analysis indicates that height, weight, hip circumference and waist circumference are dependent on body mass index in the studied populations. Probable reason for poor nutrition status among the Tolcha and Marcha of high altitude might be due to the fact that the Tolcha and Marcha of high altitude consume lesser amount of proteins, fat, milk and milk products in general than their counterpart inhabit in lower and middle altitude.     

Dietary cadmium exposure and fracture incidence among men: A population‐based prospective cohort study

Cadmium is an osteotoxic metal present in food. It causes multiple fractures in those highly exposed and is associated with reduced bone mineral density at considerably lower exposures. Little is known about fracture rates following low‐level cadmium exposure. We assessed the associations between dietary cadmium exposure and fracture incidence. Within a population‐based prospective cohort of 22,173 Swedish men, we estimated individual dietary cadmium exposure using food frequency questionnaire data and levels of cadmium in food. The average intake was 19 µg/day. Hazard ratios (HRs) for any fracture and hip fracture were estimated using Cox's regression. During 10 years of follow‐up, we ascertained 2183 cases of any fracture and 374 hip fractures by computerized linkage of the cohort to registry data. Multivariable‐adjusted dietary cadmium intake was associated with a statistically significant 19% [HR = 1.19, 95% confidence interval (CI) 1.06–1.34] higher rate of any fracture comparing highest tertile with lowest (p ≤ .01 for trend). Moreover, men in the highest tertile of dietary cadmium and lowest tertile of fruit and vegetable consumption had a 41% higher rate of any fracture compared with contrasting tertiles. Hip fracture rates also were higher in the highest tertile of cadmium intake but only statistically significant among never smokers (HR = 1.70, 95% CI 1.04–2.77). Our results indicate that dietary cadmium exposure at general population levels is associated with an increased rate of fractures among men. This association was independent of smoking and was most pronounced among men with low fruit and vegetable consumption. © 2011 American Society for Bone and Mineral Research.     

Influence of the skeletal muscle activity on time and frequency domain properties of the body surface ECG during evolving ventricular fibrillation in the pig

AIM OF THE STUDY: To evaluate influence of the skeletal muscle activity (SMA) on time and frequency domain properties of ECG during VF. MATERIALS AND METHODS: We studied the first 9min of electrically induced VF (N=7). We recorded Lead II ECG, 247 unipolar epicardial ventricular electrograms (UEGs) and 3 bipolar skeletal electromyograms (EMGs) near the positions of the ECG electrodes (sampling rate, 500Hz). We reconstructed ECG (RECG) from UEGs using forward-solution transformation matrix. Spectral properties of ECG, RECG, UEGs and MEGs were assessed in the range 2-250Hz by the median frequency (MF) and the upper limit of frequency range containing 99% of spectral energy (Flim(99)). Scaling exponent of ECG, RECG and EMGs was calculated in the ranges of 1-8 and 5-20 sampling intervals (ScE1-8 and ScE5-20, respectively). RESULTS: We observed non-monotonic increases in MF and Flim(99) of the ECG, but not UEGs and RECG, at 1-5min of VF. Maximum values of MF and Flim(99) in ECG, UEGs and RECG were (in Hz): 32+/-29 and 166+/-67; 11+/-2 and 36+/-7; 10+/-2 and 32+/-6, respectively. The transient increases in the high-frequency content of the ECG were correlated with enhanced activity in EMGs, characterized by an almost uniform spectrum in the range 2-250Hz (MF=92+/-29; Flim(99)=245+/-4Hz). Peak values of ScE(1-8) were the highest in EMGs (1.95+/-0.04), intermediate in the ECG (1.59+/-0.26), and the lowest in RECG (1.088+/-0.007). CONCLUSION: SMA significantly contributes to ECG during VF and can bias metrics used for assessment of VF organization.     

Modelling passive cardiac conductivity during ischaemia

The results of a geometric model of cardiac tissue, used to compute the bidomain conductivity tensors during three phases of ischaemia, are described. Ischaemic conditions were simulated by model parameters being changed to match the morphological and electrical changes of three phases of ischaemia reported in literature. The simulated changes included collapse of the interstitial space, cell swelling and the closure of gap junctions. The model contained 64 myocytes described by 2 million tetrahedral elements, to which an external electric field was applied, and then the finite element method was used to compute the associated current density. In the first case, a reduction in the amount of interstitial space led to a reduction in extracellular longitudinal conductivity by about 20%, which is in the range of reported literature values. Moderate cell swelling in the order of 10–20% did not affect extracellular conductivity considerably. To match the reported drop in total tissue conductance reported in experimental studies during the third phase of ischaemia, a ten fold increase in the gap junction resistance was simulated. This ten-fold increase correlates well with the reported changes in gap junction densities in the literature.