Biomedical subjects

Shanthi Krishnaswami

Publications and source records attributed to Shanthi Krishnaswami.

7 recordsLinked to original sources

PubMed2006

Platelet C4d is highly specific for systemic lupus erythematosus.

OBJECTIVE: Complement-activation product C4d is deposited on normal erythrocytes, while abnormal levels have been observed on the surface of erythrocytes of patients with systemic lupus erythematosus (SLE). This study examines whether C4d also deposits on human platelet surfaces, and whether platelet-bound C4d may provide a biomarker for SLE. METHODS: We conducted a cross-sectional study of 105 patients with SLE, 115 patients with other diseases, and 100 healthy controls. Levels of C4d on the surface of platelets were examined by flow cytometry and scanning confocal microscopy. Statistical analyses were performed to determine the clinical variables associated with platelet C4d. RESULTS: Abnormal levels of platelet C4d were found to be highly specific for SLE. Platelet C4d was detected in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared with healthy controls and 98% specific for SLE compared with patients with other diseases (P < 0.0001). In addition, platelet C4d was significantly associated with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin antibodies of the IgG (P = 0.035) or the IgM (P = 0.016) isotype. Platelet C4d was also significantly associated with SLE disease activity according to the SLE Disease Activity Index (P = 0.039), low serum C4 (P = 0.046), an elevated erythrocyte sedimentation rate (P = 0.006), and abnormal levels of C4d on erythrocytes (P < 0.0001). CONCLUSION: This observation suggests that platelet-bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic mechanisms responsible for the myriad thrombotic and vascular complications of lupus associated with antiphospholipid antibodies.

Adult↗

PubMed2005

Obesity, regional body fat distribution, and the metabolic syndrome in older men and women.

BACKGROUND: The metabolic syndrome is a disorder that includes dyslipidemia, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cardiovascular disease. We determined whether patterns of regional fat deposition are associated with metabolic syndrome in older adults. METHODS: A cross-sectional study was performed that included a random, population-based, volunteer sample of Medicare-eligible adults within the general communities of Pittsburgh, Pa, and Memphis, Tenn. The subjects consisted of 3035 men and women aged 70 to 79 years, of whom 41.7% were black. Metabolic syndrome was defined by Adult Treatment Panel III criteria, including serum triglyceride level, high-density lipoprotein cholesterol level, glucose level, blood pressure, and waist circumference. Visceral, subcutaneous abdominal, intermuscular, and subcutaneous thigh adipose tissue was measured by computed tomography. RESULTS: Visceral adipose tissue was associated with the metabolic syndrome in men who were of normal weight (odds ratio, 95% confidence interval: 2.1, 1.6-2.9), overweight (1.8, 1.5-2.1), and obese (1.2, 1.0-1.5), and in women who were of normal weight (3.3, 2.4-4.6), overweight (2.4, 2.0-3.0), and obese (1.7, 1.4-2.1), adjusting for race. Subcutaneous abdominal adipose tissue was associated with the metabolic syndrome only in normal-weight men (1.3, 1.1-1.7). Intermuscular adipose tissue was associated with the metabolic syndrome in normal-weight (2.3, 1.6-3.5) and overweight (1.2, 1.1-1.4) men. In contrast, subcutaneous thigh adipose tissue was inversely associated with the metabolic syndrome in obese men (0.9, 0.8-1.0) and women (0.9, 0.9-1.0). CONCLUSION: In addition to general obesity, the distribution of body fat is independently associated with the metabolic syndrome in older men and women, particularly among those of normal body weight.

Adipose Tissue↗

PubMed2005

Skeletal muscle fatigue, strength, and quality in the elderly: the Health ABC Study.

We examined the muscle fatigue characteristics in older men and women and determined whether these were related to the size, strength, or quality of muscle. A total of 1,512 men and women aged 70-79 yr from the Health, Aging, and Body Composition Study participated in this study. Muscle cross-sectional area and attenuation were determined with computed tomography. Skeletal muscle fatigue and strength (peak torque) of the knee extensors and flexors were measured using isokinetic dynamometry. Men were more fatigue resistant than women for both knee extension (fatigue index: 70.4 +/- 15.3 vs. 66.9 +/- 14.3%; P < 0.05) and knee flexion (67.9 +/- 16.4 vs. 64.9 +/- 17.6%; P < 0.05). Peak torque and muscle quality (specific torque) were higher in men than women for knee extension (99.6 +/- 28.2 vs. 63.0 +/- 16.8 N x m and 1.62 +/- 0.43 vs. 1.51 +/- 0.39 N x m/cm2; both P < 0.05) and for knee flexion (74.0 +/- 26.4 vs. 49.6 +/- 15.9 N x m and 2.47 +/- 1.29 vs. 2.22 +/- 0.78 N x m/cm2; both P < 0.05). Total work and power output was greater in men compared with women for both the quadriceps (1,353 +/- 451 vs. 832 +/- 264 J and 87.7 +/- 33.5 vs. 53.3 +/- 19.2 W; both P < 0.05) and the hamstrings (741 +/- 244 vs. 510 +/- 141 J and 35.4 +/- 16.0 vs. 23.7 +/- 10.2 W; both P < 0.05). In both genders, the quadriceps was able to perform more work with greater power compared with the hamstrings. Those who were stronger actually had greater fatigue after adjusting for age, race, physical activity, and total body fat. In conclusion, older men were more fatigue resistant than women, although in both men and women greater fatigue was not related to muscle weakness.

Aged↗

PubMed2005

Hyperaldosteronism and hypertension: ethnic differences.

The purpose of this study is to evaluate the relationship between aldosterone and blood pressure in a total of 220 normotensive and 293 essential hypertensive subjects in 2 genetically distinct populations-blacks and white French Canadians. The 24-hour blood pressure monitoring was performed under standardized conditions after discontinuing antihypertensive medications. Plasma renin activity and plasma aldosterone were measured in the supine position and after standing for 10 minutes. Plasma atrial natriuretic factor was also measured. Supine and standing plasma renin activities were lower (P< or =0.01), plasma aldosterone was higher (P<0.0001), and the aldosterone/renin ratios were higher (P<0.0001) in the hypertensive subjects. Atrial natriuretic factor was also higher in the hypertensive subjects (P<0.0001). Among blacks, blood pressures did not correlate with plasma renin activity. However, both average daytime and nighttime systolic and diastolic blood pressures were correlated with supine and standing plasma aldosterone and with the aldosterone/renin ratio (P<0.005 or less). In French Canadians, blood pressures tended to be positively correlated with standing plasma renin activity and aldosterone, but not with the aldosterone/renin ratio. Correlations of blood pressure with aldosterone were more consistent and more striking in blacks than in French Canadians. In both ethnic groups, there were inconsistent correlations of blood pressure with atrial natriuretic factor. These observations are consistent with the hypothesis that aldosterone-induced volume expansion is an important contributor to hypertension, especially in blacks.

Adult↗

PubMed2004

Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus.

OBJECTIVE: C4-derived activation fragments are the only complement ligands present on the surfaces of normal erythrocytes. The significance of this observation is unknown, and the role of erythrocyte-bound C4 (E-C4) in human disease has not been explored. More than any other human disease, the pathogenesis of systemic lupus erythematosus (SLE) has been characterized by defects in clearance of complement-bearing immune complexes via erythrocytes expressing complement receptor 1 (CR1). This study was undertaken to determine whether these functional defects might be reflected by abnormal patterns of E-C4 and E-CR1 expression on erythrocytes of patients with SLE. METHODS: We conducted a cross-sectional study of 100 patients with SLE, 133 patients with other diseases, and 84 healthy controls. Erythrocytes were characterized by indirect immunofluorescence and by flow cytometry for determination of levels of C4d and CR1. RESULTS: Patients with SLE had higher levels of E-C4d and lower levels of E-CR1 than did patients with other diseases (P < or = 0.001) or healthy controls (P < or = 0.001). The test was 81% sensitive and 91% specific for SLE versus healthy controls and 72% sensitive and 79% specific for SLE versus other diseases, and it had an overall negative predictive value of 92%. CONCLUSION: This is the first report of abnormal levels of E-C4d in human disease. We found that abnormally high levels of E-C4d and low levels of E-CR1 are characteristic of SLE, and combined measurement of the 2 molecules has high diagnostic sensitivity and specificity for lupus. Determination of E-C4d/E-CR1 levels may be a useful addition to current tests and criteria for SLE diagnosis.

Adult↗

PubMed2003

Bone mineral density and prevalent vertebral fractures in men and women.

To test the hypothesis that the association between bone mineral density (BMD) and estimated volumetric BMD and prevalent vertebral fractures differs in men and women, we studied 317 Caucasian men and 2,067 Caucasian women (average age 73 years). A total of 43 (14%) men and 386 (19%) women had a vertebral fracture identified on lateral spine radiographs using vertebral morphometry. Hip and spine areal BMD was about 1/3 standard deviation lower among men and women with a vertebral fracture. A 0.10 g/cm(2) decrease in areal BMD was associated with 30-40% increased odds of having a fracture in men and 60-70% increased likelihood in women. Low bone mineral apparent density (BMAD) was also associated with 40-50% increased odds of a vertebral fracture in both genders. The probability of a man having a fracture was observed at higher absolute areal BMD values than observed for women (P=values for interaction of BMD x gender: trochanter, P=0.05; femoral neck, P=0.10; total hip, P=0.09). In contrast, the probability of fracture was similar in men and women across the range of estimated volumetric BMD (BMAD). In conclusion, low BMD and low BMAD are associated with increased odds of vertebral fracture in both men and women. Measures of bone mass that partially correct for gender differences in bone size may yield universal estimates of fracture risk. Prospective studies are needed to confirm this observation.

Aged↗

PubMed2003

Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women.

OBJECTIVE: We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, and impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 2,964 elderly men and women (mean age 73.6 years) were recruited for cross-sectional comparisons of diabetes or glucose tolerance, generalized obesity with dual-energy X-ray absorptiometry, and regional body fat distribution with computed tomography. RESULTS-Approximately one-third of men with type 2 diabetes and less than half of women with type 2 diabetes were obese (BMI > or =30 kg/m(2)). Despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and IGT than in subjects with normal glucose tolerance (NGT) (11.2 +/- 9.4, 10.3 +/- 5.8, and 9.2 +/- 5.9 cm(2) for men; 12.1 +/- 6.1, 10.9 +/- 6.5, and 9.4 +/- 5.3 cm(2) for women; both P < 0.0001). Visceral abdominal fat was also higher in men and women with type 2 diabetes and IGT than in subjects with NGT (172 +/- 79, 163 +/- 72, and 145 +/- 66 cm(2) for men; 162 +/- 66, 141 +/- 60, and 116 +/- 54 cm(2) for women; both P < 0.0001 across groups). Higher rates of intermuscular fat and visceral abdominal fat were associated with higher fasting insulin in normal-weight (BMI <25 kg/m(2)) men (r = 0.24 for intermuscular fat, r = 0.37 for visceral abdominal fat, both P < 0.0001) and women (r = 0.20 for intermuscular fat, r = 0.40 for visceral abdominal fat, both P < 0.0001). These associations were not found in obese subjects. CONCLUSIONS: Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat.

Abdomen↗