The effects of metformin on maternal haemodynamics in gestational diabetes mellitus: A pilot study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major clinical challenge and is likely to remain so as the incidence of GDM continues to increase AIM: To assess longitudinal changes in maternal haemodynamics amongst women diagnosed with GDM requiring either metformin or dietary intervention in comparison to low-risk healthy controls. METHODOLOGY: Fifty-six pregnant women attending their first appointment at the GDM clinic and 60 low-risk healthy pregnant controls attending their routine antenatal clinics were recruited and assigned to three groups: GDM Metformin (GDM-M), GDM Diet (GDM-D) and Control. Non-invasive assessment of maternal haemodynamics, using recognised measures of arterial stiffness and central blood pressure (Arteriograph®), were undertaken under controlled conditions within four gestational windows: antenatal; AN1 (26-28 weeks), AN2 (32-34 weeks) and AN3 (37-40 weeks), and postnatal (PN) (6-8 weeks after delivery). Data were analysed using a linear mixed model incorporating gestational age and other relevant predictors, including age, blood pressure (BP), baseline bodyweight and pulse as fixed effects, and patient as a random effect. RESULTS: Fitted linear mixed models showed evidence of a two-way interaction effect between groups (GDM-D, GDM-M and Control) and stages of gestation (AN1, AN2, AN3 and PN) for maternal haemodynamic parameters: brachial artery augmentation index (AIx) (p=0.004), aortic AIx (p=0.008), and central systolic BP (p=0.001). However, differences in respect of aortic pulse wave velocity (p=0.001) and heart rate (p<0.001) were only significant for gestational stage. At AN2, we did not observe any evidence that the mean brachial Aix in the GDM-M was different from the control group (p=0.158). CONCLUSION: AIx and central systolic BP measures of arterial stiffness are adversely affected by GDM in comparison to controls during pregnancy. The possible beneficial effects of metformin therapy seen at 32 to 34 weeks of gestation require further exploration

Diurnal variation and repeatability of arterial stiffness and cardiac output measurements in the third trimester of uncomplicated pregnancy.

AIM: To investigate same day repeated measures and diurnal variation of arterial stiffness, cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) during the third trimester of normal pregnancy. METHODOLOGY: Pulse wave velocity (PWV) and augmentation index (AIx) were recorded using the Arteriograph, while CO, SV and TPR were recorded using noninvasive cardiac output monitoring. The measurements were obtained in the third trimester of pregnancy from 21 healthy pregnant women at four time points (morning, afternoon, evening and midnight) over a 24-h period. Triplicate measurements of 67 women were obtained at 5-min intervals to assess repeatability between measurements within a patient. RESULTS: Diurnal measurements of arterial stiffness for brachial AIx, aortic AIx and PWV were not statistically significantly different at any of the four time points. Estimated means (SD) for PWV at the four stated time points were 7.81 (2.05), 8.45 (1.68), 7.87 (1.74) and 7.64 m/s (1.15), respectively (P = 0.267). Estimates for AIx at those time points were 10.22 (15.62), 4.44 (10.07), 6.49 (10.92) and 8.40% (8.16), respectively (P = 0.295). Similarly, mean arterial pressure, SV, SV index and TPR did not show any evidence of diurnal variation. However, we observed that the mean CO, cardiac index (CI) and heart rate (HR) varied from morning to midnight; the mean CO, HR and CI increased significantly in the afternoon compared with the corresponding mean morning measurements in a similar fashion to HR. Mean (SD) CO estimates at the four stated time points were 5.90 (1.33), 6.38 (1.49), 6.18 (1.43) and 5.80 ml/min (1.19), respectively, (P < 0.001), whereas mean CI estimates were 3.65 (0.58), 3.93 (0.68), 3.81 (0.65), and 3.57 (0.48), respectively, (P < 0.001), and mean HR estimates were 95 (12), 98 (13), 95 (12) and 88 (12.98), respectively (P < 0.001). Triplicate measurements of 61 women in our repeatability study showed moderate-to-high correlation between observations on the same woman for all Arteriograph and noninvasive cardiac output monitoring variables (estimates of intraclass correlation ranged from 0.49 to 0.91). CONCLUSION: With the exception of CO, CI and HR which showed a diurnal variation, measurements of most haemodynamic parameters did not change significantly from morning to midnight, suggesting there was no evidence of systematic differences in the mean values of these variables at these time points. Multiple consecutive noninvasive measurements of vascular stiffness, CO, SV and TPR were highly correlated confirming repeatability of measurements in the third trimester of uncomplicated pregnancy, so these haemodynamic measurements do not need to be undertaken at a specific time period of the day

Does treatment modality affect measures of arterial stiffness in women with gestational diabetes?

OBJECTIVES: The incidence of gestational diabetes mellitus (GDM) is increasing and is associated with adverse maternal, fetal and neonatal outcomes. Arterial stiffness (AS) is raised in pregnancies complicated by placental-mediated diseases such as pre-eclampsia. We investigated if AS is different between healthy pregnancies and women with GDM on different treatment modalities. METHODS: We conducted a prospective longitudinal cohort study to assess and compare AS in pregnancies complicated by GDM with low-risk controls. AS, measured by pulse wave velocity (PWV) and brachial (BrAIx) and aortic (AoAIx) augmentation Index, was recorded using the Arteriograph® at four gestational windows: 24+0 to 27+6; 28+0 to 31+6; 32+0 to 35+6 and ≥36+0 weeks of gestation (windows W1-W4, respectively). Women with GDM were considered both as a single group, and as subgroups defined by treatment modality. Data were analyzed using a linear mixed model on each AS variable (log-transformed) with group, gestational windows, maternal age, ethnicity, parity, body mass index, mean arterial pressure and heart rate as fixed effects and individual as a random effect. We compared the group means including relevant contrasts and adjusted the p-values using the Bonferroni correction. RESULTS: The study population comprised 155 low-risk controls and 127 with GDM, of whom 59 were treated with dietary intervention, 47 with metformin alone and 21 with metformin plus insulin. The two-way interaction term of study group and gestational age was significant for BrAIx and AoAIx (p<0.001), though there was no evidence (p=0.729) that mean AoPWV was different between the study groups. Women in the control group demonstrated significantly lower BrAIx and AoAIX at gestational windows W1-3 compared to the combined GDM group, but not at W4. Mean (95% CI) difference in log adjusted BrAIx was -0.37 (-0.52, 0.22), -0.23 (-0.35, -0.12), and -0.29 (-0.40, -0.18) at W1, W2 and W3, respectively. Mean (95% CI) difference in log adjusted AoAIx was -0.49 (-0.69, -0.3), -0.32 (-0.47, -0.18) and -0.38 (-0.52, -0.24) at W1, W2 and W3, respectively. Similarly, women in the control group also demonstrated significantly lower BrAIx and AoAIx compared with each of the GDM treatment subgroups (diet, metformin and metformin plus insulin) at W1-3. The increase in mean BrAIx and AoAIx seen between W2 and W3 in the women with GDM treated with dietary management was attenuated in the metformin and metformin with insulin groups, however the mean differences in BrAIx and AoAIx between these treatment groups were not statistically significant at any gestational window. CONCLUSIONS: Pregnancies complicated by GDM demonstrate significantly higher AS compared to low-risk pregnancies regardless of treatment modality. Our data provides a basis for further investigation into the association of metformin therapy with changes in AS and risk of placental-mediated diseases. This article is protected by copyright. All rights reserved

Effects of steroids and angiotensin converting enzyme inhibition on circumferential strain in boys with Duchenne muscular dystrophy: a cross-sectional and longitudinal study utilizing cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiovascular magnetic resonance (CMR) derived circumferential strain (ε_cc).</p> <p>Methods</p> <p>We used CMR to assess effects of corticosteroids alone (Group A) or in combination with ACEI or ARB (Group B) on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and circumferential strain (ε_cc) in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results.</p> <p>Results</p> <p>Patients in Group A (114 studies) were younger than those in Group B (92 studies)(10 ± 2.4 vs. 12.4 ± 3.2 years, p < 0.0001), but HR, LVEF, LVEDV and LVM were not different. Although ε_ccmagnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004), age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, ε_ccworsened regardless of treatment group.</p> <p>Conclusions</p> <p>These results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.</p

Giant cervicothoracic extradural arachnoid cyst: case report

The pathogenesis, etiology, and treatment of the spinal arachnoid cyst have not been well established because of its rarity. A 57-year-old male was presented with spastic quadriparesis predominantly on the left side. His radiological examination showed widening of the cervical spinal canal and left neural foramina due to a cerebrospinal fluid - filled extradural cyst that extended from C2 to T2 level. The cyst was located left anterolaterally, compressing the spinal cord. Through a C4–T2 laminotomy, the cyst was excised totally and the dural defect was repaired. Several features of the reported case, such as cyst size, location, and clinical features make it extremely unusual. The case is discussed in light of the relevant literature

The influence of expectation on spinal manipulation induced hypoalgesia: An experimental study in normal subjects

<p>Abstract</p> <p>Background</p> <p>The mechanisms thorough which spinal manipulative therapy (SMT) exerts clinical effects are not established. A prior study has suggested a dorsal horn modulated effect; however, the role of subject expectation was not considered. The purpose of the current study was to determine the effect of subject expectation on hypoalgesia associated with SMT.</p> <p>Methods</p> <p>Sixty healthy subjects agreed to participate and underwent quantitative sensory testing (QST) to their leg and low back. Next, participants were randomly assigned to receive a positive, negative, or neutral expectation instructional set regarding the effects of a specific SMT technique on pain perception. Following the instructional set, all subjects received SMT and underwent repeat QST.</p> <p>Results</p> <p>No interaction (p = 0.38) between group assignment and pain response was present in the lower extremity following SMT; however, a main effect (p < 0.01) for hypoalgesia was present. A significant interaction was present between change in pain perception and group assignment in the low back (p = 0.01) with participants receiving a negative expectation instructional set demonstrating significant hyperalgesia (p < 0.01).</p> <p>Conclusion</p> <p>The current study replicates prior findings of c- fiber mediated hypoalgesia in the lower extremity following SMT and this occurred regardless of expectation. A significant increase in pain perception occurred following SMT in the low back of participants receiving negative expectation suggesting a potential influence of expectation on SMT induced hypoalgesia in the body area to which the expectation is directed.</p

Frequencies of BCR-ABL1 fusion transcripts among Sudanese chronic myeloid leukaemia patients

The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. In this study we report the frequencies of BCR-ABL1 fusion transcript variants studied in 43 CML patients from Sudan. The study includes 46 Sudanese patients, three of which negative for the BCR-ABL1 fusion transcript. More than half of 43 positive patients showed b2a2 fusion transcript (53.5%), while (41.9%) showed b3a2 transcript and the remaining (4.6%) coexpression of b3a2/ b2a2 and b3a2/b2a2/e19a2. We detected neither coexpression of p210/p190 nor e1a2 alone. Male patients showed a tendency to express b2a2, while female tende to express b3a2 (p = 0.017). Moreover, a single nucleotide polymorphism was detected in BCR exon 13 in one out of four patients and this patient showed only b2a2 expression. In conclusion, we observed a significant correlation between sex and type of BCR-ABL1 transcript, an observation that deserves further investigation

A Practical Platform for Blood Biomarker Study by Using Global Gene Expression Profiling of Peripheral Whole Blood

Background: Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study. Methods and Findings: We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal. Conclusion: We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study

Measurement of the top quark mass using the matrix element technique in dilepton final states

We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7  fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84  GeV

A possible role for Phlebotomus (Anaphlebotomus) rodhaini (Parrot, 1930) in transmission of Leishmania donovani

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis (VL, kala azar), caused by <it>Leishmania donovani </it>is a major health problem in Sudan and other East African countries. In this region the only proven vectors of <it>L. donovani </it>are <it>Phlebotomus orientalis </it>in eastern Sudan, Ethiopia and Upper Nile areas of Southern Sudan and <it>Phlebotomus martini </it>in Ethiopia, Kenya and Southern Sudan. In this report, we present the first evidence that <it>Phlebotomus rodhaini </it>may also play a role in maintaining transmission of <it>L. donovani </it>between animal reservoir hosts in eastern Sudan. The study was conducted in a zoonotic focus of visceral leishmaniasis in Dinder National Park, eastern Sudan, where previous work showed high infection rates of <it>L. donovani </it>in <it>P. orientalis</it>. Sand flies, captured by CDC traps were dissected and examined for infection with <it>Leishmania </it>parasites. Parasite isolates were subjected to <it>L. donovani </it>specific PCR. Field experiments were also carried out to compare efficiency of rodent baited and un-baited CDC traps in collection of <it>P. rodhaini </it>and determine its man-biting rate.</p> <p>Results</p> <p>Three female <it>P. rodhain</it>i were found infected with <it>Leishmania </it>parasites in an astonishingly small number of flies captured in three separate field trips. Two of these isolates were typed by molecular methods as <it>L. donovani</it>, while the third isolate was inoculated into a hamster that was subsequently lost. Although <it>P. rodhaini is </it>generally considered a rare species, results obtained in this study indicate that it can readily be captured by rodent-baited traps. Results of human landing collection showed that it rarely bites humans in the area.</p> <p>Conclusion</p> <p>It is concluded that <it>P. rodhaini </it>is a possible vector of <it>L. donovani </it>between animal reservoir hosts but is not responsible for infecting humans. It is suggested that the role of <it>P</it>. <it>rodhaini </it>in transmission of <it>L. donovani </it>in other zoonotic foci of visceral leishmaniasis in Africa should be re-examined.</p