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Biomedical subjects

Daniel Pella

Publications and source records attributed to Daniel Pella.

10 recordsLinked to original sources

Social class and all-cause mortality in an urban population of North India.

BACKGROUND: There is a rapid emergence of cardiovascular disease in India with economic development, leading to an increase in mortality due to these diseases. The exact causes of death in India, however, are not known. SUBJECTS AND METHODS: We studied randomly selected death records from 2222 (1385 men and 837 women) victims, aged 25-64 years, out of 3034 death records during 1999-2001 at the Municipal Corporation, Moradabad. All the families of these victims could be contacted individually to find out the causes of death, by scientists/doctors-administered pre-tested verbal autopsy questionnaires, completed with the help of spouses and local treating doctors practising in the concerned lane. Social classes were assessed by a questionnaire based on attributes of per capita income, occupation, education, housing and ownership of consumer luxury items in the household. RESULTS: Causes of mortality included infectious diseases (41.1%, n = 915) such as tuberculosis, pneumonia, chronic obstructive pulmonary disease, diarrhea/dysentery, hepatitis B, and inflammatory brain infections as the commonest causes of death in the urban population of North India. The second most common causes of death were circulatory diseases (29.1%, n = 646), including heart attacks (10.0%), strokes (7.8%), valvular heart disease (7.2%, n = 160), sudden cardiac death, and inflammatory cardiac disease (each 2.0%, n = 44). Malignant neoplasm (5.8%, n = 131), injury (14.0%, n = 313), including accidents, fire and falls, and poisonings were also quite common causes of death. Miscellaneous causes of death were noted in 9.1% (n = 202) death records, including diabetes mellitus (2.2%, n = 49), suicides (1.8%, n = 41), congenital anomalies (1.0, n = 37), dental caries infections (1.9, n = 42), and burns (1.3%, n = 33). Pregnancy and perinatal causes (0.72%, n = 15) were not commonly recorded in our study. Circulatory diseases as the cause of mortality were statistically significantly more common among higher social classes (1-3) than in lower social classes (4 and 5) whose members died more often due to infections. Heart attacks, strokes, hypertension, diabetes and obesity were statistically significantly more common among higher social classes (1-3) as compared to classes 3 and 4, but tobacco intake showed only minor differences among various classes. CONCLUSIONS: This study indicates that circulatory diseases, injury and malignant diseases have become the major causes of death in India, after infections. Members of social classes 1-3 died more often due to circulatory diseases and members in lower social classes died more often due to infections. Urbanization with rapid changes in diet and lifestyle in various social classes, and possibly aging of the population seem to be responsible for the double burden of diseases, related to under- and over-nutrition, causing death in a developing economy. Monitoring of blood pressure and heart rate around the clock for 7 days, with data analysed chronobiologically can detect abnormal circadian patterns associated with a large increase in cardiovascular disease risk, greater than hypertension itself, allowing the institution of prophylactic treatment. Such prehabilitation may be particularly useful to curb the increasing burden of cardiovascular diseases in both developed and developing countries.

Adult↗

Can brain dysfunction be a predisposing factor for metabolic syndrome?

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.

Animals↗

Mechanisms of acute myocardial infarction study (MAMIS).

Acute myocardial infarction (AMI) is a highly dynamic event, which is associated with marked neuroendocrinological dysfunction in addition to cardiac damage. The immediate trigger for AMI is not precisely known. Studies conducted by Lown, Braunwald, Halberg, Otsuka and our group have demonstrated a marked increase in sympathetic activity, oxidative stress, and magnesium and potassium deficiency during AMI. Clinical studies have reported an increased incidence of AMI, sudden death and ischemia during first quarter of the day when there is a rapid withdrawal of vagal activity and increase in sympathetic tone. In one case-control study of 202 patients with AMI, there was a significant (P < 0.02) increase in cardiac events in the second quarter of the day compared to other quarters, respectively (16.8%, 41.0%, 13.8%, 28.2% per quarter). This characteristic remained prevalent in both men and women and among patients with and without known AMI (n = 52), diabetes (n = 53) or hypertension (n = 75). Triggers of AMI were noted among 162 (82.2%) of the patients. Neuropsychological mechanisms were observed as follows: emotional stress (45.5%), sleep deprivation (27.7%), cold climate (29.2%), hot climate (24.7%), large meals (47.5%) and physical exertion (31.2%). These triggering factors are known to enhance sympathetic activity and decrease vagal tone, resulting in an increased secretion of plasma cortisol, noradrenaline, aldosterone, angiotension-converting enzyme (ACE), interleukin (IL)-1, -2, -6, -18, and tumor necrosis factor-alpha (TNF-alpha), all of which are are proinflammatory agents. There is also a deficiency in the serum levels of vitamin A, E, and C and magnesium, potassium, melatonin, and IL-10 (an anti-inflammatory agent). In our study, we found a decrease in magnesium, potassium, vitamin A, E, C and beta carotene combined with an increase in thiobarbituric acid-reactive substances (TBARS), MDA and diene conjugates, TNF-alpha and IL-6, all of which are indicators of oxidative damage and proinflammatory activity, respectively.

Activity Cycles↗

Increased concentrations of lipoprotein(a), circadian rhythms and metabolic reactions evoked by acute myocardial infarction, associated with acute reactions in relation to large breakfasts.

Of 54 patients with acute coronary artery disease (CAD) that were included in this study, 41 patients had acute myocardial infarction (AMI), five patients possible MI, four patients unstable angina and the remaining four angina pectoris. The control subjects (n = 85) were randomly selected from the general population of the city of Moradabad of similar age range after exclusion for CAD (n = 9), diabetes (n = 6) and excess intake of trans fatty acids (n = 20). The incidence of lipoprotein(a) excess (> 30 mg/dl; 42.6 vs 24.7%; P < 0.05) and mean concentration of lipoprotein(a) (Lp[a], 6.4 mg/dl, 95% confidence interval: 2.8-10.5; P < 0.05) was significantly greater in the acute CAD group compared with control subjects. Mean total cholesterol and triglycerides were significantly higher and mean nitrite level lower in the study group as compared with the control group.There was a significant greater incidence of cardiac events in the second quarter of the day compared with the fourth quarter. Lp(a), triglycerides, blood glucose, plasma insulin, malondialdehyde, diene conjugates, TBARS and TNF-alpha and IL-6 levels, which were significantly greater during the acute phase, showed a significant decline and serum nitrite and coenzyme Q demonstrated an increase at 4 weeks of follow-up when the acute reactions evoked by MI had been controlled. Large breakfasts were a predisposing factor for cardiac events in the second quarter of the day and it was significantly associated with metabolic reactions. The findings indicate that acute reactions as a result or as circadian rhythms appear to be important in the pathogenesis of AMI-associated complications and that a large breakfast in association with nitrite deficiency may further trigger the circadian rhythms. However, more studies in a larger number of subjects would be necessary in order to confirm our findings.

Acute Disease↗

Circadian heart rate and blood pressure variability considered for research and patient care.

OBJECTIVES: To review mechanisms of circadian variations in heart rate variability (HRV) and blood pressure variability (BPV) and mortality and morbidity due to cardiovascular diseases (CVD). METHODS: Results from 7-day/24-h HRV and BPV are interpreted by gender and age-specified reference values in the context of a Medline search. RESULTS: Abnormal HRV and BPV measured around the clock for 7 days provides information on the risk of subsequent morbid events in subjects without obvious heart disease and without abnormality outside the conventional (in the sense of chronobiologically unquantified) physiological range. Meditation, beta-blockers, ACE inhibitors, n-3 fatty acids and estrogens may have a beneficial influence on HRV, but there is no definitive outcome-validated therapy. Low HRV has been associated with a risk of arrhythmias and arrhythmic death, unstable angina, myocardial infarction, progression of heart failure and atherosclerosis. BPV may be characterized by treatable circadian-hyper-amplitude-tension (CHAT), which can be transient '24-h CHAT' or '7-day-CHAT', MESOR-hypertension and/or an unusually-timed (odd) circadian acrophase (ecphasia), all associated with an increased risk of stroke, stroke death, myocardial infarction, and kidney disease. CONCLUSIONS: Precise insight into the patho-physiology in time of HRV and BPV is needed with development of a consensus on best measures of HRV for clinical purposes and to determine when a 7-day record interpreted chronobiologically suffices and when it does not, for detection within as well as outside the conventional normal range, for diagnostic clinical practice and to direct therapy of risk greater than that associated with hypertension, smoking or any other risk factor.

Blood Pressure↗

Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction.

In a randomized, double-blind, controlled trial, the effects of oral treatment with coenzyme Q10 (CoQ10, 120 mg/day), a bioenergetic and antioxidant cytoprotective agent, were compared for 1 year, on the risk factors of atherosclerosis, in 73 (CoQ, group A) and 71 (B vitamin group B) patients after acute myocardial infarction (AMI). After 1 year, total cardiac events (24.6 vs. 45.0%, p < 0.02) including non-fatal infarction (13.7 vs. 25.3%, p < 0.05) and cardiac deaths were significantly lower in the intervention group compared to control group. The extent of cardiac disease, elevation in cardiac enzymes, left ventricular enlargement, previous coronary artery disease and elapsed time from symptom onset to infarction at entry to study showed no significant differences between the two groups. Plasma level of vitamin E (32.4 +/- 4.3 vs. 22.1 +/- 3.6 umol/L) and high density lipoprotein cholesterol (1.26 +/- 0.43 vs. 1.12 +/- 0.32 mmol/L) showed significant (p < 0.05) increase whereas thiobarbituric acid reactive substances, malondialdehyde (1.9 + 0.31 vs. 3.1 + 0.32 pmol/L) and diene conjugates showed significant reduction respectively in the CoQ group compared to control group. Approximately half of the patients in each group (n = 36 vs. 31) were receiving lovastatin (10 mg/day) and both groups had a significant reduction in total and low density lipoprotein cholesterol compared to baseline levels. It is possible that treatment with CoQ10 in patients with recent MI may be beneficial in patients with high risk of atherothrombosis, despite optimal lipid lowering therapy during a follow-up of 1 year. Adverse effect of treatments showed that fatigue (40.8 vs. 6.8%, p < 0.01) was more common in the control group than CoQ group.

Adult↗

Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial.

BACKGROUND: The rapid emergence of coronary artery disease (CAD) in south Asian people is not explained by conventional risk factors. In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid, we assessed the benefits of this diet for patients at high risk of CAD. METHODS: We did a randomised, single-blind trial in 1000 patients with angina pectoris, myocardial infarction, or surrogate risk factors for CAD. 499 patients were allocated to a diet rich in whole grains, fruits, vegetables, walnuts, and almonds. 501 controls consumed a local diet similar to the step I National Cholesterol Education Program (NCEP) prudent diet. FINDINGS: The intervention group consumed more fruits, vegetables, legumes, walnuts, and almonds than did controls (573 g [SD 127] vs 231 g [19] per day p<0.001). The intervention group had an increased intake of whole grains and mustard or soy bean oil. The mean intake of alpha-linolenic acid was two-fold greater in the intervention group (1.8 g [SD 0.4] vs 0.8 g [0.2] per day, p<0.001). Total cardiac end points were significantly fewer in the intervention group than the controls (39 vs 76 events, p<0.001). Sudden cardiac deaths were also reduced (6 vs 16, p=0.015), as were non-fatal myocardial infarctions (21 vs 43, p<0.001). We noted a significant reduction in serum cholesterol concentration and other risk factors in both groups, but especially in the intervention diet group. In the treatment group, patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group. INTERPRETATION: An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet.

Angina Pectoris↗