Profile of anemia in acute lymphoblastic leukemia patients on maintenance therapy and the effect of micronutrient supplementation.

BACKGROUND: Anemia is a common finding and important cause of morbidity in patients with acute lymphoblastic leukemia (ALL) at diagnosis or during the course of its protracted treatment. We studied profile of anemia in ALL patients on maintenance therapy and evaluated specific micronutrients as cause of this anemia. PATIENTS AND METHODS: ALL patients who were on maintenance therapy and had grade ≥ 2 anemia were recruited for the study. Serum iron studies, folate, and vitamin B12 were done to identify micronutrient deficiency and to initiate supplementation with specific components if found to be deficient. Toxicities, improvement of anemia, micronutrient levels, and disease outcome were studied after 3 months. RESULTS: From March 2015 to September 2016, 105 ALL patients were found to be on maintenance fulfilling the inclusion criteria. Overall, the proportion of anemia was 80%(N = 84). Majority had normocytic normochromic anemia (71%). Macrocytic anemia was seen in 18% and microcytic hypochromic in 9.5%. In patients with anemia of grade ≥ 2 (N = 84), 38 patients (45%) had biochemical deficiency of serum folate, and 7 (8%) had vitamin B12 deficiency. No biochemical evidence of iron deficiency was found. Supplementation of deficient micronutrients improved anemia: mean hemoglobin significantly increased from 8.06 ± 1.63 to 10.78 ± 1.53 (p < 0.001) at 3 months; and reduced treatment toxicities, mean number of febrile neutropenia episodes (p = 0.007), and treatment interruptions of > 2 weeks (p = 0.002) were lowered. Patients with anemia had significantly more relapses (N = 14,64%) compared to patients without anemia (N = 8,36%), (p = 0.040). CONCLUSION: Timely identification and correction of micronutrient deficiencies causing anemia in ALL patients on maintenance can enhance treatment outcomes.

Irisin and Visfatin Predicts Severity of Diabetic Nephropathy.

Although the roles of irisin and visfatin have been well established in diabetes mellitus, there are limited studies about their association in diabetic nephropathy. The present study was designed to assess the levels of irisin and visfatin and their association with the severity of diabetic nephropathy. 43 diabetic nephropathy cases and 43 diabetic subjects without nephropathy were enrolled in the study. Serum levels of irisin and visfatin were compared in both the groups. Irisin and visfatin were significantly increased in diabetic nephropathy cases when compared with diabetes subjects without nephropathy. eGFR was negatively correlated with visfatin (r = -0.323, p = 0.034), irisin (r = -0.324, p = 0.034), urine albumin (r = -0.443, p = 0.003) and albumin creatinine ratio (r = -0.419, p = 0.005) in patients with diabetic nephropathy. Visfatin was significantly elevated in stage IV nephropathy compared with stage III nephropathy. We conclude that irisin and visfatin are elevated in diabetic nephropathy and can be an index of its severity.

Elevated interleukin-17 and reduced testosterone in bipolar disorder. Relation with suicidal behaviour.

Hormonal imbalance and inflammation are associated with bipolar disorder and suicidal behavior. The present study was designed to assess the levels of testosterone and interleukin-17 and their association with suicidal behavior in patients with bipolar disorder in remission. 41 bipolar disorder cases in remission and 41 age matched controls were enrolled in the study. Testosterone and interleukin-17 levels were assessed in both the groups. Interleukin-17 was significantly increased and testosterone was significantly reduced in bipolar disorder when compared with controls. IL-17 was negatively correlated with testosterone (r = -0.368, p = 0.018) and positively correlated with duration of disease (r = 0.382, p = 0.014) in bipolar disorder patients. Both didn't show any association with suicidal behavior. We conclude that testosterone is increased and interleukin-17 is reduced in bipolar disorder in remission and these were not associated with suicidal behavior in these patients.

Laparoscopic ovarian drilling reduces serum homocysteine levels in women with Polycystic Ovary Syndrome.

OBJECTIVE: To investigate the effect of laparoscopic ovarian drilling (LOD) on homocysteine levels and clinical outcomes in women with Polycystic Ovary Syndrome (PCOS). STUDY DESIGN: The study was conducted in JIPMER, Puducherry. Fifty PCOS subjects who were admitted for LOD were enrolled in the study. Serum homocysteine levels were estimated in all the subjects before and after LOD. Paired t-test was used to compare the homocysteine levels before and after LOD. RESULTS: LOD reduces homocysteine levels (p < .001), improves the rate of ovulation (38/50) and clinical pregnancy (21/50) in PCOS. When subgroup analysis was done, LOD significantly reduced homocysteine levels in ovulatory and conceived groups. Between the conceived and non conceived groups, the reduction was more significant (p = 0.001) in conceived group, when compared with non conceived group. CONCLUSIONS: LOD reduces homocysteine levels and improves clinical outcome in PCOS.

Hypoadiponectinemia, elevated iron and high-sensitivity C-reactive protein levels and their relation with prostate size in benign prostatic hyperplasia.

Elevated iron, high-sensitivity C-reactive protein (CRP) and hypoadiponectinemia are known to initiate tumour development. There is paucity of data regarding the above-mentioned parameters and their relation with prostate size in benign prostatic hyperplasia (BPH). The present study was designed to assess the levels of iron, hs-CRP and adiponectin levels and their association with prostate size in BPH patients. A total of 37 BPH cases and 36 controls were enrolled in the study. Iron, hs-CRP and adiponectin were estimated in both the groups. Iron and hs-CRP were significantly increased and adiponectin was significantly reduced in BPH cases when compared with controls. Iron (r = .397, p = .015), hs-CRP (r = .341, p = .039) and adiponectin (r = -.464, p = .004) were significantly associated with prostate size in BPH cases. Multivariate linear regression analysis showed that iron acts as predictor of prostate size in BPH (R2  = 0.395, ß = 0.526, p = .001). We conclude that iron and hs-CRP are elevated and adiponectin is reduced in BPH cases and associated with prostate size.

Effects of vitamin D and calcium supplementation on side effects profile in patients of breast cancer treated with letrozole.

BACKGROUND: Vitamin D deficiency (<10ng/mL) and insufficiency (10-30ng/mL) may contribute to musculoskeletal symptoms observed in patients taking letrozole. This study was undertaken to assess the vitamin D status in breast cancer patients who received letrozole for >2months and to see the effects of vitamin D3 and calcium supplementation on them. METHODS: Eighty-two breast cancer patients were included. Baseline serum 25-hydroxy vitamin D concentrations were assayed and standard questionnaire was completed. They were given vitamin D3 and calcium supplementation (2000IU/1000 mg and 4000IU/1000mg) based on their baseline serum 25-hydroxy vitamin D concentration for 12weeks. RESULTS: Baseline serum 25-hydroxy vitamin D concentrations showed that 13.4% of patients were deficient and 73.2% of patients were insufficient in 25-hydroxy vitamin D. There was an increase in the concentrations of calcium, phosphorus and decrease in the concentrations of parathyroid hormone, alkaline phosphatase as the concentration of serum 25-hydroxy vitamin D increases. Patients who received letrozole for a longer duration had a low concentration of serum 25 (OH) vitamin D. Vitamin D3 and calcium supplementation increased the concentrations of calcium, phosphorous and decreased the concentrations of parathyroid hormone and alkaline phosphatase. Patients who had low serum 25-hydroxy vitamin D concentrations had more musculoskeletal symptoms which was improved following supplementation (9.14 vs 8.10 p=0.000). CONCLUSION: Vitamin D3 supplementation significantly improved serum 25-hydroxy vitamin D concentrations and decreased letrozole-induced arthralgia.

Using optimal combination of teaching-learning methods (open book assignment and group tutorials) as revision exercises to improve learning outcome in low achievers in biochemistry.

Graduate medical students of India are taught Biochemistry by didactic lectures and they hardly get any opportunity to clarify their doubts and reinforce the concepts which they learn in these lectures. We used a combination of teaching-learning (T-L) methods (open book assignment followed by group tutorials) to study their efficacy in improving the learning outcome. About 143 graduate medical students were classified into low (<50%: group 1, n = 23), medium (50-75%: group 2, n = 74), and high (>75%: group 3, n = 46) achievers, based on their internal assessment marks. After the regular teaching module on the topics "Vitamins and Enzymology", all the students attempted an open book assignment without peer consultation. Then all the students participated in group tutorials. The effects on the groups were evaluated by pre and posttests at the end of each phase, with the same set of MCQs. Gain from group tutorials and overall gain was significantly higher in the low achievers, compared to other groups. High and medium achievers obtained more gain from open book assignment, than group tutorials. The overall gain was significantly higher than the gain obtained from open book assignment or group tutorials, in all three groups. All the three groups retained the gain even after 1 week of the exercise. Hence, optimal use of novel T-L methods (open book assignment followed by group tutorials) as revision exercises help in strengthening concepts in Biochemistry in this oft neglected group of low achievers in graduate medical education. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):321-325, 2016.

Pre-hypertension: Is it an inflammatory state?

Even though several studies have implicated the role of inflammation in the pathogenesis of hypertension and other cardiovascular disease, there are only limited studies about inflammatory markers in prehypertension. The objective of the present article was to review the role of markers like C-reactive protein, interleukin-6, tumor necrosis factor-α and sialic acid in prehypertension. An extensive literature search was made in Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/) using phrases such as prehypertension, inflammation, C-reactive protein, cardiovascular disease, cytokines and sialic acid. Several investigators have reported increased inflammatory markers like C-reactive protein, interleukin-6, tumor necrosis factor-α and sialic acid in prehypertension indicating the role of inflammation in the pathogenesis of prehypertension and its complications. Elevated inflammatory markers may enhance the risk for cardiovascular disease in subjects with prehypertension.

Association between prolactin and thyroid hormones with severity of psychopathology and suicide risk in drug free male schizophrenia.

BACKGROUND: Hormonal deregulation is associated with suicidal risk in various psychiatric disorders. Thyroid hormones and prolactin play a role in the pathophysiology of schizophrenia. The present study aimed to analyze thyroid hormones and prolactin levels in patients with schizophrenia, and to explore its association with disease severity and suicide risk. METHODS: Thirty-eight cases and 38 controls were included in the study. Serum thyroid hormones and prolactin were estimated in all the subjects. Disease severity was assessed using the Positive and Negative Syndrome Scale and suicidal ideations were assessed using the Columbia Suicide Severity Rating Scale. RESULTS: Serum prolactin (p=0.004) and free T4 (p=0.029) were significantly elevated in the schizophrenia group as compared to controls. Serum prolactin was significantly associated with higher negative symptom scores (r=0.418, p=0.008), but not positive symptoms or general psychopathology of schizophrenia. Thyroid hormones were not associated with disease severity scores. Suicidal ideas were more common in schizophrenia patients with higher free T4 (p=0.011). CONCLUSION: Prolactin and free T4 were increased in patients with schizophrenia as compared to controls. Suicidal ideation was associated with increased free T4, but not prolactin levels.

Pentraxin-3 and nitric oxide as indicators of disease severity in alcoholic cirrhosis.

Recent studies have indicated that pentraxin-3 can be used as a marker to assess the severity of hepatic fibrosis in non-alcoholic steatohepatitis. The present study was designed to assess pentraxin-3, nitric oxide and tumour necrosis factor-α (TNFα) in alcoholic cirrhosis and their association with disease severity. We enrolled 47 alcoholic cirrhosis cases and 32 controls. Serum pentraxin-3, nitric oxide (NO) and TNFα levels were estimated in both groups. Serum pentraxin-3, NO and TNFα were significantly increased in alcoholic cirrhosis patients compared to controls. Pentraxin-3 had a significant positive correlation with TNFα (r=0.303, P=0.039), Child-Pugh score (r=0.394, P=0.006) and MELD score (r=0.291, P=0.047) in alcoholic cirrhosis cases. Also we found positive association between NO with Child-Pugh score (r=0.391, P=0.007) and MELD score (r=0.311, P=0.033) in these cases. Linear regression analysis shows significant association of pentraxin-3 and NO (ß=0.375, r2=0.141, P=0.009). We conclude that elevated pentraxin-3 and NO levels are associated with severity of alcoholic cirrhosis.

Identification of mistakes and their correction by a small group discussion as a revision exercise at the end of a teaching module in biochemistry.

BACKGROUND: Graduate medical students often get less opportunity for clarifying their doubts and to reinforce their concepts after lecture classes. The Medical Council of India (MCI) encourages group discussions among students. We evaluated the effect of identifying mistakes in a given set of wrong statements and their correction by a small group discussion by graduate medical students as a revision exercise. METHODS: At the end of a module, a pre-test consisting of multiple-choice questions (MCQs) was conducted. Later, a set of incorrect statements related to the topic was given to the students and they were asked to identify the mistakes and correct them in a small group discussion. The effects on low, medium and high achievers were evaluated by a post-test and delayed post-tests with the same set of MCQs. RESULTS: The mean post-test marks were significantly higher among all the three groups compared to the pre-test marks. The gain from the small group discussion was equal among low, medium and high achievers. The gain from the exercise was retained among low, medium and high achievers after 15 days. CONCLUSION: Identification of mistakes in statements and their correction by a small group discussion is an effective, but unconventional revision exercise in biochemistry.

Hyperhomocysteinemia and hyperlipoproteinemia (a) in obese South Indian men: an indication for increased cardiovascular risk.

Obesity is a pathological condition which increases the risk for cardiovascular disease. The present study was designed to evaluate homocysteine, lipoprotein (a) [Lp(a)], apolipoprotein-B (apo-B), apolipoprotein-A-I (apo-A-I) and lipid indices and their association if any in obese South Indian men. Thirty obese men and thirty age-matched males with normal body weight (controls) were recruited in the study. Plasma homocysteine, Lp(a), lipid profile, apo-A-I and apo-B were estimated in all the subjects. Lipid indices such as lipid pentad index (LPI), lipid tetrad index (LTI), atherogenic index of plasma (AIP), non-high density lipoprotein (non-HDL)/high density lipoprotein (HDL) ratio and apo-B/apo-A-I ratio were calculated in all study subjects. Homocysteine, Lp(a), apo-B, apo-B/apo-A-I ratio and lipid indices were significantly increased in obese men, compared to controls. Both homocysteine and Lp(a) were positively correlated with BMI, waist, hip circumference and apo-B and negatively correlated with apo-A-I. Also we found highly significant positive correlation between homocysteine and Lp(a) levels. The data from the present study concludes that non-conventional risk factors like homocysteine, Lp (a), apo-B/apo-A-I ratio, LTI, LPI, non-HDL/HDL ratio and AIP were significantly elevated in obese Indian men, suggesting they are more prone to develop cardiovascular disease, than the age-matched men with normal body weight.

Formulation of multiple choice questions as a revision exercise at the end of a teaching module in biochemistry.

The graduate medical students often get less opportunity for clarifying their doubts and to reinforce their concepts after lecture classes. Assessment of the effect of MCQ preparation by graduate medical students as a revision exercise on the topic "Mineral metabolism." At the end of regular teaching module on the topic "Mineral metabolism," graduate medical students were asked to prepare the stems of 15 MCQs based on the four discriminators given for each. They were told that one of the discriminators could be the answer for the MCQ and the remaining three could be the distracters. They were further guided in their task by providing few key word(s) in the stem of the expected MCQ. In the first phase of the exercise, the students attempted the MCQ preparation individually without peer consultation. In the second phase, the students participated in small group discussion to formulate the best MCQs of the group. The effects on low, medium, and high achievers were evaluated by pre and post-tests with the same set of MCQs. Both the individual endeavor in Phase 1 and small group discussion in Phase 2 for the formulation of MCQs significantly contributed to the gain from the exercise. The gains from the individual task and from small group discussion were equal among the different categories of students. Both phases of the exercise were equally beneficial for the low, medium, and high achievers. The high and medium achievers retained the gain from the exercise even after 1 week of the exercise whereas the low achievers could not retain the gain completely. Formulation of MCQs is an effective and useful unconventional revision exercise in Biochemistry for graduate medical students.

Acute intermittent porphyria: diagnosis per chance.

OBJECTIVES: To report a case of acute intermittent porphyria (AIP) diagnosed by chance during routine investigations. CLINICAL PRESENTATION AND INTERVENTION: A 21-year-old female presented with vague gastrointestinal symptoms. Upon admission, she was disoriented. Later she developed generalized seizures and was treated with phenytoin, but the condition worsened. Upon investigation, her liver function, renal function, blood sugar level and electrolytes were within normal limits. When kept for routine laboratory testing, the color change in urine prompted us to investigate for porphyria. It was positive for phorphobilinogen (PBG) and urophorphyrin. Since AIP had been diagnosed, the initial treatment with phenytoin was discontinued with a favorable outcome. A screening test for PBG in urine by Ehrlich's reagent was performed on the patient's mother and was positive. CONCLUSION: A high degree of suspicion at the laboratory can also determine the diagnosis of AIP, which is often missed by the clinician.

Short-term heart variability and oxidative stress in newly diagnosed essential hypertension.

We sought to evaluate oxidative stress parameters like malondialdehyde, total antioxidant status, and time, frequency domain heart rate variability indices in newly diagnosed untreated hypertension. We also sought to study the correlation between heart rate variability and oxidative stress parameters in normotensive and newly diagnosed untreated essential hypertensives. Fourteen normotensive males and 36 newly diagnosed male hypertensives were enrolled for the study. Malondialdehyde, total antioxidant status, and heart rate variability in the frequency and time domain were studied in the hypertensive and normotensive group. Malondialdehyde was significantly higher in the hypertensive group, whereas total antioxidant status was significantly higher in the control group. SDNN, RR triangular index, RMSSD, log(10) low-frequency power, log (10) high-frequency power, log (10) total power, and heart rate variability during deep breathing test was significantly lower in hypertensive patients compared to normotensive controls. SDNN, RMSSD, high-frequency power, and high-frequency power normalized had significant negative correlation with malondialdehyde. Low-frequency power normalized positively correlated with malondialdehyde. Total antioxidant status had a significant negative correlation with blood pressure. The study gives further evidence for a decreased heart rate variability and elevated oxidative stress in hypertension.

Association between protein bound sialic acid and high sensitivity C-reactive protein in prehypertension: a possible indication of underlying cardiovascular risk.

The global burden posed by cardiovascular disease due to a rising incidence of known risk factors like essential hypertension underlines an urgent need to identify other potential risk factors like dyslipidemia, elevated levels of high-sensitivity CRP (hsCRP), Apo-B, and sialic acid in prehypertensive subjects. This study sought to examine the possible alteration in the levels of hsCRP, plasma protein bound sialic acid, and other lipid risk factors and the possible interactions among these parameters in prehypertensive subjects. Forty prehypertensive and 34 normotensive male subjects were enrolled in the study. Lipid profile, hsCRP, Apo-B, sialic acid, and lipid risk ratios were estimated in both the groups. There was no significant difference between fasting glucose and BMI in either group. The levels of total cholesterol, triglycerides, direct LDL-cholesterol, non-HDL cholesterol, and Apo-B were significantly increased in prehypertensive subjects compared with controls. The risk ratios calculated as direct LDL-cholesterol/Apo-B, total cholesterol/HDL-cholesterol, non-HDL-cholesterol/HDL-cholesterol were significantly elevated in prehypertensive subjects. There was also a significant increase in hsCRP and protein bound sialic acid in prehypertensive subjects in comparison with normotensive subjects. Correlation analysis revealed a significant association between the protein bound sialic acid with hsCRP, LDL cholesterol, and LDL-C/Apo-B. The findings of the present study suggest that in prehypertension, there is an association between protein bound sialic acid and hsCRP that reflects the clustering of cardiovascular risk factors in these subjects.

Altered insulin sensitivity, insulin secretion and lipid profile in non-diabetic prostate carcinoma.

Insulin can influence cancer risk through its effect on cell proliferation, differentiation and apoptosis. Although hyperinsulinemia is considered as a risk factor in the pathogenesis of various cancers, the data related to insulin sensitivity, insulin secretion and lipid profile is lacking in non-diabetic prostate carcinoma cases. The present study was undertaken to evaluate lipid profile parameters and insulin sensitivity and secretion using surrogate markers derived from the measurements of fasting glucose and fasting insulin. The study group comprises 27 prostate carcinoma cases and 27 controls having similar age. Fasting serum insulin, glucose and lipid profile parameters were estimated in both the groups. Insulin sensitivity was assessed by Homeostasis model assessment of insulin sensitivity and Quantitative insulin sensitivity check index. Insulin secretion was assessed by insulinogenic index. Fasting serum insulin, insulinogenic index and LDL-cholesterol were significantly increased (p < 0.05) and HOMA-IS, QUICKI and HDL-cholesterol was significantly decreased (p < 0.05) in carcinoma cases compared to controls. PSA level was significantly associated with fasting insulin (R2 = 0.150, beta = 0.387, p = 0.046) and QUICKI (R2 = 0.173, beta = -0.416, p = 0.031). Fasting insulin was significantly correlated with triglyceride (r = 0.404, p = 0.037) and HDL-cholesterol (r = -0.474, p = 0.013). The present study concludes that hyperinsulinemia associated with reduced insulin sensitivity may play a role in the pathogenesis of prostate carcinoma.

Benign prostatic hyperplasia: dietary and metabolic risk factors.

Benign prostatic hyperplasia (BPH) is the most common nonmalignant condition of the prostate occurring in ageing men. Even though BPH is a major public health problem, causing high morbidity and substantial worsening in men's quality of life, little is known about its risk factors. Several studies revealed that it is a multifactorial disease. Previous studies have documented family history, hormonal imbalance, and growth factors as etiological factors in the development of BPH. This review focuses on the dietary and metabolic risk factors including diabetes mellitus, hypertension, obesity, hyperinsulinemia, as well as dyslipidemia and their mechanisms in the pathogenesis of BPH.