Atypical Cardiac Autonomic Neuropathy Identified with Entropy Measures.

Aims: To identify Cardiac Autonomic Neuropathy (CAN) from a range of measures extracted from Heart Rate Variability (HRV), including higher moments of RR intervals and a spectrum of entropy measures of RR intervals. Study Design: Analysis of HRV measured from participants at a diabetes screening clinic. Groups were compared using t-tests to identify variables that provide separation between groups. Place and Duration of Study: Charles Sturt Diabetes Complications Clinic, Albury, NSW Australia. Methodology: Eleven participants with definite CAN, 67 participants with early CAN, and 71 without CAN had their beat-to-beat fluctuations analyzed using two spectra of HRV: the spectrum of moments of RR intervals and the spectrum of Renyi entropy measures. RR intervals were extracted from ECG recordings and were detrended before analysis. Results: Higher moments of RR intervals identified a previously unnoticed sub-group of patients who are atypical within the definite CAN group. Classification of CAN progression was better with Renyi entropy measures than with moments of RR intervals. Significant differences between early and definite CAN were found with the sixth and eighth moments, (P=.022 and P=.042 respectively), but for entropy measures P values were orders of magnitude smaller. Conclusion: Identification of early CAN provides the opportunity for early intervention and better treatment outcomes, as well as identifying atypical cases. Our findings illustrate the value of exploring a range of different measures when attempting to detect differences in groups of patients with CAN.

Impaired Fasting Glucose & 8-Iso- Prostaglandin F2a in Diabetes Disease Progression.

Aims: The objective of the present study was to evaluate the changes of 8- isoprostaglandin F2α and other markers of oxidative stress with impaired fasting glucose when compared to non-diabetic control participants. Methodology: This is a cross-sectional study, conducted at Charles Sturt University, Albury, NSW, Australia and included 428 participants (female: male, 247:181) participants attending the Diabetes Complications Clinic in the School of Community Health for the period between January 2011 to October 2012. Results: Urinary 8-isoprostaglandin F2α was significantly greater in the impaired fasting glucose group (1.4±1.3ng/ml) compared to control group (0.68±0.5ng/ml, P= .05). The increase in urinary 8-isoprostaglandin F2α was associated with a significant elevation in serum total cholesterol (4.7±1.1mol/L, P= .04) and a significant reduction in high density lipoprotein cholesterol (1.4±0.4mmol/L, P= .02) in the impaired fasting glucose group compared to the control group. A significant negative correlation was noted between urinary 8-isoprostaglandin F2α and high-density lipoprotein cholesterol among all the participants included in this study (P= .05). Conclusions: The current study proves the importance of measuring markers of oxidative stress, expressed by urinary 8-isoprostaglandin F2α and serum lipids in managing cases of impaired fasting glucose and suggests a useful biomarker for assessing disease progression and/or remission, especially in the prediabetic state.

Assessment of Mean Vessel Density and Angiogenesis in Endometrial Carcinomas.

Objective: To evaluate the role of angiogenesis in tumor growth by the assessment of mean vessel density and to quantify angiogenesis as an important variable in endometrial cancers. Material and Methods: 53 cases of endometrial malignancies (epithelial tumors-36 cases and metastatic tumors-17 cases), were analysed for histological types, grades and features like depth of invasion and vascular invasion. Microvessel counts were performed by examining the microvessels thoroughly in terms of count, morphology and density after staining the tissues by hematoxylin & eosin stain, reticulin and immunostain (Antifactor VIII Ag). Results: On H&E stain - Microvessel density (MVD) in endometrial malignancy ranged from 3.0 - 13.5 and mean MVD was 8.78. On Reticulin stain - MVD ranged from 3.5 - 15.2 and mean MVD was 9.76. Antifactor VIII sections showed very small microvessels or even single endothelial cells with the highest total counts and the MVD ranged from 6.5- 16.8 with Mean MVD of 11.7. The counts increased with the grade of the tumor in the absence of necrosis or haemorrhage. MVD counts also increased with the stage, being 8.12 in Stage I disease, 8.65 in Stage II and 10.8 in stage III disease. Atypical hyperplasia was found to be associated with epithelial tumors in 8 cases, making it a significant finding. Conclusion: Role of angiogenesis assumes greater significance with increasing severity of lesions, higher grade and stage of the tumor and seems to have an important diagnostic and prognostic significance.

Glutathione: Glutathione Sulfide Redox Imbalance in Early Impaired Fasting Glucose.

Aim: The current study aims to examine the balance between glutathione and glutathione sulfide and how this was disturbed in patients with impaired fasting glucose (IFG) level. The study also included 8-hydroxy-2’-deoxyguanosine to provide a more comprehensive picture of the overall redox state. Methodology: A cross-sectional analysis of ninety medication free participants without reported history of cardiovascular disease and/or diabetes mellitus was undertaken with data collected from the Diabetes Complications Research Initiative database at Charles Sturt University. Fasting blood glucose, HbA1c and cholesterol as standard markers for diabetes mellitus and associated complications were measured in addition to the emerging biomarkers glutathione (GSH), glutathione disulfide (GSSG), and urinary 8- hydroxy-2’-deoxyguanosine (8OHdG). Results: The IFG group had a mean blood glucose level above 6.1mmol/L being significantly higher compared to control (P<0.001). Traditional clinical markers were all within the normal range for both groups. However the GSH/GSSG ratio (8.53±5.4 vs 6.62±2.2, P=.04) was significantly lower in the IFG group. GSH and 8OHdG, being markers for oxidative stress, were not significantly different between the two groups. Conclusion: The free radical related changes in metabolic redox pathways are linked to oxidative stress and related pathologies but may not be associated with disease progression, providing an explanation why conflicting results are presented in the literature concerning any individual biomarkers and risk of diabetes. Our study included individuals with no medication use and mild hyperglycemia (impaired fasting glucose) and indicates a pro-oxidant response to mild-moderate hyperglycemia with a moderate rise in oxidative DNA damage.

Oxidative DNA Damage in Gestational Diabetes Mellitus: Correlation with Antioxidants in an Iraqi Cohort.

This study aimed to evaluate the degree of oxidative stress in gestational diabetes mellitus when compared to non-diabetic pregnant women. Methodology: This cross-sectional study included 73 participants (29 gestational diabetic women and 44 control pregnant women) attending the Maternal and Childhood Unit, Al- Husayniya Medical Centre, Baghdad, Iraq. The data was analyzed using SPSS (Version 14) and Microsoft Excel (Office2007, Microsoft). All values were expressed as mean±standard deviation (M±SD). Results: Serum 8-Hydroxy-2-Deoxyguanosine was significantly (P < .001) greater in the gestational diabetes mellitus group compared to control group (57.2±17.6 ng/dl versus 19.8±7.8ng/dl respectively). The increase in 8-Hydroxy-2-Deoxyguanosine was associated with a significant (P < .001) elevation in serum malondialdehyde level (2.1±0.8 nmol/ml versus 1±0.4 nmol/ml) and a significant (P =.05) reduction in plasma reduced glutathione in the gestational diabetes mellitus group compared to the control group (20.6±5 mg/dl compared to 24.1±4.4 mg/dl). A significant change in total cholesterol (5.4±1.1mmol/L) and low density lipoprotein cholesterol (3.3±0.9mmol/L) were also noted in gestational diabetes mellitus group compared to the control group (4.7±1.3mmol/L and 2.8±1mmol/L respectively) at P =.05. Conclusion: An increase in 8-Hydroxy-2-Deoxyguanosine is associated with higher levels of malondialdehyde and a significant reduction in reduced glutathione in gestational diabetes mellitus group, suggesting that significant oxidative stress associated with lipid peroxidation is occurring. Measuring these markers is useful in monitoring gestational diabetes mellitus to prevent the negative outcomes of gestational diabetes mellitus such as increased risk of diabetes and fetal morbidity.

Assessment of a Cardiac Rehabilitation Program Based on the Borg RPE Scale by Six-minute Walk Test: A Pilot Study.

Aims: The ability of cardiac rehabilitation to reduce mortality in those with cardiovascular disease is well established. Despite its widespread use in the clinical setting, the Borg Rating of Perceived Exertion (RPE) scale is yet to be validated for its ability to lead to improvements in functional capacity. Study Design: A closed cohort pilot study. Place and Duration of Study: Department of Physiotherapy, Albury Base Hospital and School of Community Health, between November 2008 and November 2009. Methodology: Fifteen participants were assessed prior to and following completion of a cardiac rehabilitation program. Exercise was prescribed according to the Borg RPE scale. Pre and post Six-Minute Walk Test (6MWT) scores were obtained to determine the impact of the cardiac rehabilitation program. Results: Fifteen cardiac rehabilitation participants completed all requirements of the study after an initial enrolment of 22 patients. Wilcoxon signed-ranks test showed statistically significant improvements in 6MWT scores following participation in the cardiac rehabilitation program (p=.033) from a median value of 412 metres to 475 metres. Conclusion: In this pilot study, cardiac rehabilitation programs based on the Borg RPE scale may improvefunctional capacity measured by 6MWT during a 6-week period.

Prevalence and Severity of ECG Anomalies in a Rural Australian Population.

Aims: To determine the prevalence and severity of cardiac arrhythmias in a rural Australian population using ECG assessment. Study Design: This is a University-based research project. Comparative design with random samples used. Place and Duration of Study: School of Community Health, Charles Sturt University, Albury, NSW, Australia. Methodology: Five hundred and eight participants with or without a known history of cardiovascular disease were recruited via public media announcements indicating a health screening opportunity carried out at the local university. Their medical history was obtained and a 12-lead electrocardiography (ECG) was recorded. ECG recordings were classified into severity and prevalence determined in each category. The number of participants that had to be referred and had follow-up by the general practitioner was determined. Results: Moderate to severe ECG anomalies, which included atrial fibrillation or left bundle branch block were identified in 58 (11.4%) of the participants. Forty (7.9%) individuals with ECG anomalies were referred to the general practitioner for further evaluation. Eight participants did not seek further advice. Twenty-two (68.8%) participants that made an appointment to see their general practitioner were either commenced on treatment, had their treatment changed or received surgery. A further 85 (16.7%) of individuals required regular follow-up in line with their ECG characteristics and other health information, presenting with non-clinical ECG changes that had the potential for adverse health outcomes in the future including long QT interval, right bundle branch block or left ventricular hypertrophy for instance. Conclusion: Our study has demonstrated that a substantial number of patients in this rural community have both ECG abnormalities and or cardiac arrhythmias that required regular review or commencement of treatment by their doctor.