Hematological Abnormalities in Alcoholics

BACKGROUND: Alcohol consumption has increased considerably in the past 25 years, the need for accurate methods for detection and monitoring of alcohol related problems in different health care settings is clearly considerable. Despite such a need, there is no exact clinical finding or symptom in a patient history that is sufficiently sensitive and specific to detect alcohol related problem in its early phase. The clinical signs of alcohol abuse are rather minimal in the early phase of this process while most of the signs arise later after several years of excessive drinking. Also alcohol consumption is usually under-reported in interviews; alcohol abusers tend to underestimate their drinking even more than the social drinkers. The reasons for using biological laboratory markers are that they give objective information about alcohol consumption and changes in drinking habits. Among these laboratory markers hematological abnormalities appear earlier that Alcohol effect on hematopoeitic system are both direct & indirect, its also dose dependent, The direct consequences of excessive alcohol consumption include toxic effects on the bone marrow; suppress the production of all blood cell precursors. Alcohol’s indirect effects include nutritional deficiencies that impair the production and function of various blood cells. Among the hematological abnormalities Increased MCV values have been observed in 64-89% of alcohol abusers. Increased MCV values are also found in cases of vitamin B12 and folic acid deficiency, liver diseases, several haematological disorders, hypothyroidism, in users of antiepileptics. Alcohol abuse has been found to explain increased MCV values in 89% of men and 56% of women in general practice. MCV return to normal after 3 months of abstinence. n biochemical abnormalities & also reversible with abstinence. AIMS AND OBJECTIVES: The aim of our study was to investigate the alterations of hematological markers in a population of alcohol dependent individuals since the need for sensitive biological markers to detect and prove recent drinking has been the focus of many research groups. Decision making about the role of alcohol as an aetiological factor for these abnormalities in motivating patients to change their drinking habits by demonstrating the reversal of these abnormalities after abstinence. METHODS: Setting:Department of Medicine, Govt. Rajaji Hospital, Madurai Medical College,Madurai.Inclusion criteria: Age 20-40 yr, Alcohol consumption 210 gms of ethanol/week in males & 100gm of ethanol/week in females for minimum of one year .Exclusion criteria : Patients with Liver disease, Viral hepatitis, Renal disease, Known Thyroid diseases, Hematological malignancies, h/o drug intake that alter hematological profile, Immunosuppressed individual, Other co-morbid illness. DESIGN OF STUDY: Prospective observational study. PERIOD OF STUDY: 6 Months from November 2015 to April 2016. PARTICIPANTS: 100 patients in the age group of 20-40 years with history of alcohol consumption 210 gms/week in males & 100 gms /week in females for minimum one year admitted with another primary admitting diagnosis in Department of Medicine, Government Rajaji Hospital METHOD: 100 patients admitted in medical ward with another primary diagnosis are selected based on the inclusion/exclusion criteria & history is obtained from each patient based on the previously prepared proforma & clinical examination. USG abdomen & pelvis ,viral markers will be done to rule out pre existing alcoholic liver disease, blood samples collected &sent for complete hemogram, peripheral smear, serum B12 assay will be done in all patients to screen for pre existing B12 deficiency . RESULTS: In our study we included 100 patients after applying inclusion & exclusion criteria, short history & clinical examination are done in all patients. All the patients were screened for serum B12 levels, MCV, Peripheral smear, CDT, GGT values are done in all patients. In our study we included 100 patients between 20-40 years of age, incidentally all of them are males,13% are less than or equal to 25 years,29% are between 26-30 years of age,30% between 31-35 years & 28 % are between 36-40 years of age. In the 100 patients we enquired about their drinking habits & looked for MCV, GGT, CDT, Spur cells & Pancytopenia in peripheral smear, serum B12 levels, 11% had pancytopenia & 4% had spurcells in peripheral smear which are statistically significant, As the duration of alcohol increases the incidence of pancytopenia & presence of spur cells increases. As the duration of alcohol & quantity of consumption increases serum B12 values decreases, as the B12 value decreases the incidence of Pancytopenia increases, Hence the incidence of Pancytopenia has positive correlation both to duration & quantity of alcohol intake. There is a significant positive correlation between quantity & duration of alcohol intake & rise in CDT levels. There is a significant positive correlation between quantity & duration of alcohol intake & rise in CDT levels. MCV rises as the duration & quantity of alcohol intake increases which is independent of serum B12 levels. As the quantity & duration of alcohol intake increases the serum B12 levels & Platelet count decreases. CONCLUSION: Alcohol has numerous adverse effects on the various types of blood cells and their functions. For example, heavy alcohol consumption can cause generalized Suppression of blood cell production resulting in Pancytopenia & thrombocytopenia and the production of structurally abnormal blood cell precursors like spur cells that cannot mature into functional cells, apart from that there is a significant rise in CDT ,GGT levels & also there is rise in MCV both megaloblastic & non megaloblastic macrocytosis occurs in significant percentage with the reduction in serum B12 levels, hence these parameters could be considered as markers of alcohol abuse. Due to the limited sensitivity of any single laboratory marker, the parallel measurement of CDT with traditional alcohol markers may enhance the ability to detect alcohol abuse. studies indicate that the combined measurement of CDT and GGT or of CDT and MCV could achieve such an enhancement

INTEGRAL SOLUTIONS

We obtain the non-trival integral solutions for quartic Diaphoptine equations with two variables is presented. A few numerical examples are given

Electrochemical behaviour of dimethyl hydrazones - part – 1 cyclohexanone dimethyl hydrazone

The polarographic behaviour of cyclohexanone dimethyl hydrazone at dropping mercury electrode in aqueous alcoholic medium has been investigated in presence of 0.1 M KC1 as supportingelectrolyle.The effect of depolariser concentration, pH, and drop time on the wave characteristics and the reaction mechanism occurring at the surface of the mercury drop electrode have been studied. Well defined ineversible diffusion controlled two cathodic waves were obtained in this medium between the DH ranae 6 and 8.2 and a single wave of irreversible and diffusion controlled nature was obtained between the pH12 to 6 and 8.210 10.4. a, n. and 'n' values and electrochemical reaction order of the system were calculated. The linearity of the diffu%on current with concentration of the depolariser provides a rapid and precise method for the estimation of this dimethyl hydrazone in the concentration down to 10-4 M in aqueous alcoholic medium

Effect of chronic sinusitis on middle ear function.

A wide variety of diseases of the nose and paranasal sinuses may affect the function of the eustachian tube and consequently that of the middle ear. The common cold, allergic rhinitis and acute and chronic sinusitis may lead to the obstruction of the eustachian tube orifice with all the attendant consequences for the middle ear. If pathological changes occur in the nasal or paranasal sinus mucosa and the nature of secretions alter, the normal secretion routes may undergo significant changes and the two major routes may join before they reach the eustachian tube orifice, and one or both routes may form whorls around or even in the orifice itself. Abnormal infected secretions may then move directly over the eustachian tube orifice causing congestion and obstruction of the orifice due to the inflammation of its lymphoreticular tissue with slowing down of the muco ciliary clearance and may lead to impeded ventilation and/or ascending infection of the middle ear. The damage of middle ear function becomes more serious with the extent of lesion and with the longer course of the disease in the para nasal disease. Though hearing was unaffected in the study group a significantly high (65%) had elevated air conduction thresholds. Sinusitis involving the posterior groups were more likely to cause middle ear dysfunction. Middle ear volumes largely remained normal in the study groups. Patients with sclerosed mastoids are more likely to adjust poorly with negative pressures

Association between type 2 diabetes and changes in myocardial structure, contractile function, energetics, and blood flow before and after aortic valve replacement in patients with severe aortic stenosis

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of left ventricular dysfunction after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Persistent impairments in myocardial energetics and myocardial blood flow (MBF) may underpin this observation. Using phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance, this study tested the hypothesis that patients with severe AS and T2D (AS-T2D) would have impaired myocardial energetics as reflected by the phosphocreatine to ATP ratio (PCr/ATP) and vasodilator stress MBF compared with patients with AS without T2D (AS-noT2D), and that these differences would persist after AVR. METHODS: Ninety-five patients with severe AS without coronary artery disease awaiting AVR (30 AS-T2D and 65 AS-noT2D) were recruited (mean, 71 years of age [95% CI, 69, 73]; 34 [37%] women). Thirty demographically matched healthy volunteers (HVs) and 30 patients with T2D without AS (T2D controls) were controls. One month before and 6 months after AVR, cardiac PCr/ATP, adenosine stress MBF, global longitudinal strain, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk distance were assessed in patients with AS. T2D controls underwent identical assessments at baseline and 6-month follow-up. HVs were assessed once and did not undergo 6-minute walk testing. RESULTS: Compared with HVs, patients with AS (AS-T2D and AS-noT2D combined) showed impairment in PCr/ATP (mean [95% CI]; HVs, 2.15 [1.89, 2.34]; AS, 1.66 [1.56, 1.75]; P<0.0001) and vasodilator stress MBF (HVs, 2.11 mL min g [1.89, 2.34]; AS, 1.54 mL min g [1.41, 1.66]; P<0.0001) before AVR. Before AVR, within the AS group, patients with AS-T2D had worse PCr/ATP (AS-noT2D, 1.74 [1.62, 1.86]; AS-T2D, 1.44 [1.32, 1.56]; P=0.002) and vasodilator stress MBF (AS-noT2D, 1.67 mL min g [1.5, 1.84]; AS-T2D, 1.25 mL min g [1.22, 1.38]; P=0.001) compared with patients with AS-noT2D. Before AVR, patients with AS-T2D also had worse PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.66 [1.56, 1.75]; P=0.04) and vasodilator stress MBF (AS-T2D, 1.25 mL min g [1.10, 1.41]; T2D controls, 1.54 mL min g [1.41, 1.66]; P=0.001) compared with T2D controls at baseline. After AVR, PCr/ATP normalized in patients with AS-noT2D, whereas patients with AS-T2D showed no improvements (AS-noT2D, 2.11 [1.79, 2.43]; AS-T2D, 1.30 [1.07, 1.53]; P=0.0006). Vasodilator stress MBF improved in both AS groups after AVR, but this remained lower in patients with AS-T2D (AS-noT2D, 1.80 mL min g [1.59, 2.0]; AS-T2D, 1.48 mL min g [1.29, 1.66]; P=0.03). There were no longer differences in PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.51 [1.34, 1.53]; P=0.12) or vasodilator stress MBF (AS-T2D, 1.48 mL min g [1.29, 1.66]; T2D controls, 1.60 mL min g [1.34, 1.86]; P=0.82) between patients with AS-T2D after AVR and T2D controls at follow-up. Whereas global longitudinal strain, 6-minute walk distance, and NT-proBNP all improved after AVR in patients with AS-noT2D, no improvement in these assessments was observed in patients with AS-T2D. CONCLUSIONS: Among patients with severe AS, those with T2D demonstrate persistent abnormalities in myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function after AVR; AVR effectively normalizes myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function in patients without T2D

Cardiovascular magnetic resonance phenotyping of heart failure with mildly reduced ejection fraction

Aims The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40–49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF. Methods and results Patients (N = 300, 62.7 ± 13 years, 63% males) with a clinical diagnosis of heart failure with no angina symptoms, history of myocardial infarction, or coronary intervention were prospectively recruited. Patients underwent clinical assessment and CMR including T1 mapping, extracellular volume (ECV) mapping, late gadolinium enhancement, and measurement of myocardial blood flow at rest and maximal hyperaemia. Of 273 patients in the final analysis, 93 (34%) patients were categorized as HFmrEF, 46 (17%) as heart failure with preserved ejection fraction (HFpEF), and 134 (49%) as heart failure with reduced ejection fraction (HFrEF). Nineteen (20%) patients with HFmrEF had evidence of occult ischaemic heart disease. Diffuse fibrosis and hyperaemic myocardial blood flow were similar in HFmrEF and HFpEF, but HFmrEF showed significantly lower native T1 (1311 ± 32 vs. 1340 ± 45 ms, P < 0.001), ECV (24.6 ± 3.2 vs. 26.3 ± 3.1%, P < 0.001), and higher myocardial perfusion reserve (2.75 ± 0.84 vs. 2.28 ± 0.84, P < 0.001) compared with HFrEF. Conclusion Patients with HFmrEF share most phenotypic characteristics with HFpEF, including the degree of microvascular impairment and fibrosis, but have a high prevalence of occult ischaemic heart disease similar to HFrEF. Further work is needed to confirm how the phenotype of HFmrEF responds to medical therapy

Phenotyping hypertrophic cardiomyopathy using cardiac diffusion magnetic resonance imaging: the relationship between microvascular dysfunction and microstructural changes

Aims Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) is predictive of clinical decline, however underlying mechanisms remain unclear. Cardiac diffusion tensor imaging (cDTI) allows in vivo characterization of myocardial microstructure by quantifying mean diffusivity (MD), fractional anisotropy (FA) of diffusion, and secondary eigenvector angle (E2A). In this cardiac magnetic resonance (CMR) study, we examine associations between perfusion and cDTI parameters to understand the sequence of pathophysiology and the interrelation between vascular function and underlying microstructure. Methods and results Twenty HCM patients underwent 3.0T CMR which included: spin-echo cDTI, adenosine stress and rest perfusion mapping, cine-imaging, and late gadolinium enhancement (LGE). Ten controls underwent cDTI. Myocardial perfusion reserve (MPR), MD, FA, E2A, and wall thickness were calculated per segment and further divided into subendocardial (inner 50%) and subepicardial (outer 50%) regions. Segments with wall thickness ≤11 mm, MPR ≥2.2, and no visual LGE were classified as ‘normal’. Compared to controls, ‘normal’ HCM segments had increased MD (1.61 ± 0.09 vs. 1.46 ± 0.07 × 10−3 mm2/s, P = 0.02), increased E2A (60 ± 9° vs. 38 ± 12°, P < 0.001), and decreased FA (0.29 ± 0.04 vs. 0.35 ± 0.02, P = 0.002). Across all HCM segments, subendocardial regions had higher MD and lower MPR than subepicardial (MDendo 1.61 ± 0.08 × 10−3 mm2/s vs. MDepi 1.56 ± 0.18 × 10−3 mm2/s, P = 0.003, MPRendo 1.85 ± 0.83, MPRepi 2.28 ± 0.87, P < 0.0001). Conclusion In HCM patients, even in segments with normal wall thickness, normal perfusion, and no scar, diffusion is more isotropic than in controls, suggesting the presence of underlying cardiomyocyte disarray. Increased E2A suggests the myocardial sheetlets adopt hypercontracted angulation in systole. Increased MD, most notably in the subendocardium, is suggestive of regional remodelling which may explain the reduced subendocardial blood flow

4D Flow Cardiac MR in Primary Mitral Regurgitation

Background Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. Purpose To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. Study Type Prospective, single-center, two arm, interventional vs. nonintervention observational study. Population Forty-four patients (male N = 30; median age 68 [59–75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing “watchful waiting” (WW). Field Strength/Sequence 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). Assessment Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). Statistical Tests Included Student t-test/Mann–Whitney test/Fisher's exact test, Bland–Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. Results While Bland–Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement −36 mL to 65 mL), than between 4DF-MR and TTE (bias −8; limits of agreement −106 mL to 90 mL) and PMRI and TTE (bias −23; limits of agreement −105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). Data Conclusion This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation