Biomedical subjects
Publications and source records attributed to V George.
The essential oil obtained by hydrodistillation of the rhizomes of Amomum cannicarpum was analyzed by GC and GC/MS. Thirty-four compounds were identified, of which the major components were beta-terpineol (13.4%), beta-pinene (9.4%) and alpha-pinene (6.9%). The essential oil showed significant antimicrobial activity.
To investigate whether functional polymorphisms exist in the C-reactive protein (CRP) gene, i.e., ones that contribute directly to differences in baseline CRP among individuals, we sequenced a 1,156-nucleotide-long stretch of the CRP gene promoter in 287 ostensibly healthy people. We identified two single-nucleotide polymorphisms (SNPs), a bi-allelic one at nucleotide -409 (G-->A), and a tri-allelic one at -390 (C-->T-->A), both resident within the hexameric core of transcription factor binding E-box elements. Electrophoretic mobility shift assays confirmed that the SNP within the sequence (-412)CACGTG(-407) (E-box 1) modulates transcription factor binding, and that the one within (-394)CACTTG(-389) (E-box 2) supports transcription factor binding only when the -390 T allele is present. The commonest of four E-box 1/E-box 2 haplotypes (-409G/-390T) identified in the population supported highest promoter activity in luciferase reporter assays, and the rarest one (-409A/-390T) supported the least. Importantly, serum CRP in people with these haplotypes reproduced this rank order, i.e., people with the -409G/-390T haplotype had the highest baseline serum CRP (mean +/- SEM 10.9 +/- 2.25 microg/ml) and people with the -409A/-390T haplotype had the lowest (5.01 +/- 1.56 microg/ml). Furthermore, haplotype-associated differences in baseline CRP were not due to differences in age, sex, or race, and were still apparent in people with no history of smoking. At least two other SNPs in the CRP promoter lie within E-box elements (-198 C-->T, E-box 4, and -861 T-->C, E-box 3), indicating that not only is the quality of E-box sites in CRP a major determinant of baseline CRP level, but also that the number of E-boxes may be important. These data confirm that the CRP promoter does encode functional polymorphisms, which should be considered when baseline CRP is being used as an indicator of clinical outcome. Ultimately, development of genetic tests to screen for CRP expression variants could allow categorization of healthy people into groups at high versus low future risk of inflammatory disease.
NIR-FT Raman and FT-IR spectra of columbianadin, extracted from seeds and roots of Heracleum candolleaum, were recorded and analyzed. The vibrational frequencies of the compound have been computed using semi-empirical AM1 method and compared with experimental values. The C=O stretching frequencies of the carbonyl groups have been lowered due to conjugation. The CH stretching and bending vibrations of CH3 groups of the ester part indicate the presence of hyperconjugation effect. Characteristic ring vibrations have also been identified.
The petroleum ether and methanol extracts of rhizomes of Amomum cannicarpum exhibited moderate inhibiting activity against both Gram-positive and Gram-negative bacteria. None of the extractives was active against the tested moulds.
BACKGROUND: The impact of diet on blood pressure and the age-related changes in blood pressure have been difficult to detect within one population. We designed this analysis to study the association of major dietary factors with blood pressure and with age-related changes in blood pressure in a representative sample of the US population. METHODS: Data were obtained on all individuals 20 years or older (n = 17 030) surveyed in the Third National Health and Nutrition Examination Survey (NHANES III), including demographic data, anthropometric data, dietary intake (sodium, potassium, calcium, magnesium, protein, alcohol, and total energy) based on 24-hour recall, and blood pressure. Multivariate models relating diet to blood pressure were constructed using stepwise regression, best subset regression, and multiple regression. RESULTS: Systolic blood pressure was positively associated with higher sodium, alcohol, and protein intakes (P<.05) and negatively associated with potassium intake (P =.003). Diastolic blood pressure was negatively associated with potassium and alcohol intakes (P<.001). Pulse pressure was positively associated with sodium, protein, and alcohol intakes (P<.001). A higher intake of calcium (P =.01) was associated with a lower rate of rise in systolic blood pressure with age. CONCLUSION: A diet low in sodium, alcohol, and protein is associated with lower systolic blood and pulse pressure. Potassium intake was associated with lower systolic and diastolic blood pressure, whereas alcohol intake was associated with lower diastolic blood pressure. In addition, the age-related changes in systolic blood pressure were attenuated by higher calcium and protein intakes. Magnesium was not associated with any changes in blood pressure.
The Hutterite and Collaborative Study on the Genetics of Asthma data sets provided by Genetic Analysis Workshop 12 were analyzed using a regression-based transmission/disequilibrium test that assesses linkage between a marker locus and quantitative trait locus when allelic association is present, as proposed by George et al. [Am J Hum Genet 65:236-45, 1999]. Because the same marker set and analytical technique was used, the results from these data sets are amenable for comparison. Statistically significant results common to both data sets were found on chromosomes 1 and 3. A noteworthy result, significant at p < 10(-4), was detected on chromosome 18 in the Hutterites.
Over the past few years at least 13 transmission/disequilibrium test (TDT)-based tests have been developed for quantitative (Q) traits for the assessment of association or linkage in the presence of the other. A total of six of these QTDT methods were used to analyze log10IgE in the Collaborative Study on the Genetics of Asthma data set. Only moderate agreement was found between the tests. The results of the QTDT analyses were only slightly affected by the use of gender and age as covariates. Results from analysis of IgE and log10IgE were inconsistent. Our conclusion is that there is only modest agreement among the QTDT methods examined, covariates should be used even if they have a small effect, and that data should be normalized before analysis.
Accurate diagnosis of micrometastases in sentinel lymph nodes of cutaneous melanoma is critical for proper clinical management. S-100 protein and HMB-45 are the traditional immunomarkers widely used for this purpose. However, the interpretation of micrometastases by these markers is difficult with significant reduction in the diagnostic accuracy. S-100 protein demonstrates immunoreactivity for other nonmelanoma cells and obscures nuclear details, which are crucial for the interpretation of single cell metastases. We compared the new melanoma markers, Melan-A (clone A103) and MART-1 (clone M2-7C10), with S-100 protein and HMB-45, by examining 77 formalin-fixed paraffin-embedded sections of sentinel lymph nodes from 13 cases of primary cutaneous melanoma. CD68 (PG-M1) and hematoxylin-eosin-stained sections were also studied. Four pathologists interpreted the staining pattern after concealing the identity of each immunomarker. Az values (area under receiver operating characteristic curve) with receiver operating characteristic curve were higher with Melan-A (0.9742) and MART-1 (0.9779) compared with S-100 protein (0.8034) and HMB-45 (0.8651), demonstrating a higher diagnostic accuracy with Melan-A and MART-1 with superior detection of melanoma micrometastases. Melan-A and MART-1 showed sharp cytoplasmic immunoreactivity, almost exclusively restricted to the melanoma cells. Therefore, Melan-A and MART-1 are recommended for the evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma as a routine alternative to S-100 protein and HMB-45.
The variable (V-) region repertoire of antibodies (Abs) to Haemophilus influenzae capsular polysaccharide (Hib PS) has been extensively studied in individuals vaccinated against the microbe, but to a lesser extent in subjects who generated such Abs in response to a 'natural' encounter with this microbe or its antigenic mimics. To gain an insight into the repertoire of Hib PS-reactive Abs in vaccinated and non-vaccinated individuals, we used a monoclonal Ab, 3H1, which detects an idiotypic marker associated with an Ab V-region gene, V3-23. We show here that Hib PS-reactive Abs with detectable 3H1 idiotope can be quantified by an indirect inimunoezymatic assay in serum samples of non-vaccinated healthy adults as well as of recently vaccinated healthy infants. The percentage of Abs that was simultaneously Hib PS-reactive and 3H1-positive ranged widely (from 0 to 68%) among individual serum samples from both groups of subjects. No dramatic differences in the expression of 3H1 idiotope on Hib PS-reactive Abs were found between vaccinated and non-vaccinated individuals. Our results are consistent with the hypothesis that the utilization of V-region genes in Hib PS-reactive Abs that individuals generate after a 'natural' encounter with Hib PS or its mimics is similar to that in these Abs elicited by Hib PS conjugate vaccines.
BACKGROUND: During the past decade, the number of children with asthma increased; however, the number of asthma hospitalizations for children decreased. OBJECTIVE: To assess the proportion of high-severity cases among children hospitalized with asthma and the association of high-severity asthma with patient and hospital characteristics. DESIGN: The data set used was the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. Records were selected of patients 18 years and younger who had the principal diagnosis of asthma. Records were analyzed of 29077 patients at 746 hospitals in 1990 and 33 443 patients at 811 hospitals in 1995. Asthma severity was classified by All Patient Refined-Diagnosis-Related Groups. Cross-sectional logistic regression analysis was performed using survey data analysis software. RESULTS: The most common diagnoses associated with high-severity asthma were respiratory distress and respiratory failure. The proportion of high-severity asthma cases did not change significantly between 1990 (4.2%) and 1995 (4.6%) (P = .08). Adolescents and boys were more likely to have high-severity asthma than children aged 5 to 12 years and girls. Western, southern, and north-central hospitals and urban teaching hospitals had a higher proportion of high-severity asthma cases than northeastern hospitals and nonteaching hospitals. CONCLUSIONS: Between 1990 and 1995, the proportion of high-severity cases among children hospitalized with asthma did not change significantly. However, patient age, sex, region of the country, and hospital teaching status were associated with variations in the proportion of high-severity asthma cases.
The diagnostic role of intraoperative cytology (IC) has been demonstrated by many comparative studies. These studies have used sensitivity and specificity as statistical tools, based on binary principles. Statistical methods based on binary principles appear to be inappropriate for comparing anatomic pathology studies which involve significant human judgment with a range of subjective nonbinary result patterns. In this study, we applied the receiver operating characteristic (ROC) curve, which is based on probabilistic principles for the comparison of diagnostic accuracy with IC and frozen sections (FS). Seven observers studied a variable number of IC alone, FS alone, and IC/FS together from a pool of 446 specimens. The results were analyzed by ROC curve, using the MEDCALC software program (MedCalc Software, Mariakerke, Belgium). The accuracy with IC alone and FS alone was comparable. IC alone was diagnostic for many lesions, offering the choice of not freezing the tissue, and thus avoiding the introduction of artifacts. This strongly favors the routine practice of preparing IC during intraoperative consultation.
BACKGROUND: This paper examines participation rates and the association between participation and study outcomes (% energy from fat) among participants in the Women's Health Trial: Feasibility Study in Minority Populations, a randomized clinical trial to determine if ethnically and socioeconomically diverse women could be recruited and make significant dietary changes. METHODS: Women (n = 2,208) were recruited from three clinical centers and randomized to either an intervention group or a control group. Multiple measures were collected at 6 months. RESULTS: Participation rates for follow-up data collection activities were high (average participation 79%). Hispanics and lower educational groups participated significantly less (59% for Hispanics vs 86% for blacks and whites; 78% for lowest educational group vs 84% for highest educational group). Intervention participation significantly predicted change in percentage energy from fat (P < 0.001), accounting for an additional 8% of variance after background variables were controlled for. CONCLUSIONS: These data suggest that intervention participation is positively related to dietary change, but they cannot rule out the possibility that other factors may influence both of these factors.
The isolation and NMR spectra of 2-exo,3-endo-camphanediol (1) and 2-pinene-4,10-diol (2) from the seeds of Heracleum candolleanum are reported.
UNLABELLED: Laryngoscopy and tracheal intubation (LTI) often provoke an undesirable increase in blood pressure (BP) and/or heart rate (HR). We tested the premise that nicardipine (NIC) and esmolol (ESM) in combination (COMB) would oppose both. Adult surgical patients received pretreatment (randomized) with IV bolus NIC 30 microg/kg (n = 31), ESM 1.0 mg/kg (n = 34), or COMB (one-half dose each, n = 32). Peak BP and HR after LTI were compared with controls (CONT; n = 35) with no pretreatment. Anesthetic induction was standardized: IV thiopental (5-7 mg/kg), fentanyl (1-2 microg/kg), and succinylcholine (1.5 mg/kg). Systolic (S), diastolic (D), and mean (M) BP and HR awake before pretreatment (baseline) were similar in all test groups. No patient was treated for hypotension, bradycardia, or tachycardia after pretreatment or anesthetic induction. Peak HR after LTI was increased versus baseline in CONT and all test groups, but did not differ from CONT among the test groups. Peak SBP and DBP increased versus baseline in CONT, and with ESM and NIC, but not COMB. Peak SBP, DBP, and MBP were increased with ESM versus COMB, and peak DBP with ESM versus NIC. Compared with no pretreatment before the IV induction of general anesthesia, the peak increase in BP after LTI is best blunted by the combination of nicardipine and ESM, compared with either drug alone. No single drug or combination in the doses tested opposed increased HR. IMPLICATIONS: Compared with no pretreatment before the IV induction of general anesthesia, the peak increase in blood pressure after laryngoscopy and tracheal intubation is best blunted by the combination of nicardipine and esmolol, compared with either drug alone. No single drug or combination in the doses tested opposed increased heart rate.
Spontaneous bacterial peritoneal infections is recognized as a very common complication of cirrhotic ascites, but isolation of fungus in pure culture from ascitic fluid is relatively rare, even more so in the human immunodeficiency virus (HIV)-negative or nonimmunocompromised hosts. We describe two patients of spontaneous fungal peritonitis where the isolate was Cryptococcus neoformans. Both cases suffered from hepatitis B virus (HBV) infection. The clinical and laboratory profiles of both patients were similar to those of conventional spontaneous bacterial peritonitis. We suggest that it would be prudent to heighten clinical suspicion for fungal peritonitis in such cases.
Our long-term objective is to identify genes whose expression results in hypertension and in phenotypic changes that may contribute to hypertension. The purpose of the present study was to describe evidence for the heritability of hypertension-related phenotypes in hypertensive, hyperlipidemic black sib pairs. Outpatient anthropomorphic measurements were obtained in >200 affected sib pairs. In addition, 68 of these sib pairs were studied under controlled, standardized conditions at an inpatient clinical research center while off both antihypertensive and lipid-lowering medications. Heritability was estimated on the basis of sib-sib correlations and with an association model. Higher heritability estimates for blood pressure were observed with multiple measurements averaged over 24 hours than with measurements at a single time point, and heritability estimates for nighttime blood pressures were higher than those for daytime blood pressures. Heritability estimates for several of the phenotypes were augmented by obtaining measurements in response to a standardized stimulus, including (1) blood pressure responses to the assumption of upright posture, standardized psychological stress, and norepinephrine infusion; (2) plasma renin, aldosterone, epinephrine, and cAMP and cGMP responses to the assumption of upright posture; (3) para-aminohippurate and inulin clearances in response to norepinephrine infusion; and (4) plasma arginine vasopressin in response to NaCl infusion. High heritability estimates were also observed for various measures of body size and body fat, left ventricular size, cardiac index, stroke volume, total peripheral resistance, and serum concentrations of LDL and HDL cholesterol and leptin. These heritability estimates identify the hypertension-related phenotypes that may facilitate the identification of specific genetic determinants of hypertension in blacks with hyperlipidemia.
The purpose of this study was to identify risk factors for pediatric asthma emergency department (ED) visits. A cross-sectional sample of 307 families (24%) responded to a mailed survey. Respondents were similar to the target population of 2487 children with asthma. Thirty-seven percent of respondents had two or more asthma ED visits in the past year. Asthma ED use was associated with persistent asthma symptoms, parents without high school diplomas, age under 4 years, African-American race/ethnicity, use of written care plans, and use of spacers at school. The latter two variables were associated with severe asthma. High-risk children can be targeted for office-based medical care.
INTRODUCTION: Short-term and long-term results of renal transplantation have improved over the past 15 years. However, there has been no change in the prevalence of recurrent and de novo diseases. A retrospective study was initiated through the Renal Allograft Disease Registry, to evaluate the prevalence and impact of recurrent and de novo diseases after transplantation. MATERIALS AND METHODS: From October 1987 to December 1996, a total of 4913 renal transplants were performed on adults at the Medical College of Wisconsin, University of Cincinnati, University of California at San Francisco, University of Louisville, University of Washington, Seattle, and Washington University School of Medicine. The patients were followed for a minimum of 1 year. A total of 167 (3.4%) cases of recurrent and de novo disease were diagnosed by renal biopsy. These patients were compared with other patients who did not have recurrent and de novo disease (n=4746). There were more men (67.7% vs. 59.8%, P<0.035) and a higher number of re-transplants (17% vs. 11.5%, P<0.005) in the recurrent and de novo disease group. There was no difference in the rate of recurrent and de novo disease according to the transplant type (living related donor vs. cadaver, P=NS). Other demographic findings were not significantly different. Common forms of glomerulonephritis seen were focal segmental glomerulosclerosis (FSGS), 57; immunoglobulin A nephritis, 22; membranoproliferative glomerulonephritis (GN), 18; and membranous nephropathy, 16. Other diagnoses include: diabetic nephropathy, 19; immune complex GN, 12; crescentic GN (vasculitis), 6; hemolytic uremic syndrome-thrombotic thrombocytopenic purpura (HUS/TTP), 8; systemic lupus erythematosus, 3; Anti-glomerular basement membrane disease, 2; oxalosis, 2; and miscellaneous, 2. The diagnosis of recurrent and de novo disease was made after a mean period of 678 days after the transplant. During the follow-up period, there were significantly more graft failures in the recurrent disease group, 55% vs. 25%, P<0.001. The actuarial 1-, 2-, 3-, 4, and 5-year kidney survival rates for patients with recurrent and de novo disease was 86.5%, 78.5%, 65%, 47.7%, and 39.8%. The corresponding survival rates for patients without recurrent and de novo disease were 85.2%, 81.2%, 76.5%, 72%, and 67.6%, respectively (Log-rank test, P<0.0001). The median kidney survival rate for patients with and without recurrent and de novo disease was 1360 vs. 3382 days (P<0.0001). Multivariate analysis using the Cox proportional hazard model for graft failure was performed to identify various risk factors. Cadaveric transplants, prolonged cold ischemia time, elevated panel reactive antibody, and recurrent disease were identified as risk factors for allograft failure. The relative risk (95% confidence interval) for graft failure because of recurrent and de novo disease was 1.9 (1.57-2.40), P<0.0001. The relative risk for graft failure because of posttransplant FSGS was 2.25 (1.6-3.1), P<0.0001, for membranoprolifera. tive glomerulonephritis was 2.37 (1.3-4.2), P<0.003, and for HUS/TTP was 5.36 (2.2-12.9), P<0.0002. There was higher graft failure (64.9%) and shorter half-life (1244 days) in patients with recurrent FSGS. CONCLUSION: In conclusion, recurrent and de novo disease are associated with poorer long-term survival, and the relative risk of allograft loss is double. Significant impact on graft survival was seen with recurrent and de novo FSGS, membranoproliferative glomerulonephritis, and HUS/TTP.