Genetic linkage analysis of human hemoglobin variants.
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Biomedical subjects
Publications and source records attributed to T Reed.
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Maximal grip strength was measured in kilograms using a hand dynamometer on 344 unrelated males between the ages of 59 and 70 participating in the third examination of the NHLBI Twin Study. There was a significant linear decline in mean grip strength over this age range. Mean grip strength and grip strength per kilogram weight are presented for age 59, ages 60-64 and 65-69. Genetic analysis using 127 pairs of identical (MZ) twins and 130 pairs of fraternal (DZ) twins indicated significant genetic effects for absolute grip strength and grip strength per kilogram weight. The largest estimate of heritability (65%) was obtained for grip strength adjusted for significant effects of weight, height, age, and various anthropometric measures of fatness, muscle mass, and frame size.
White-matter hyperintensities (WMHI) are frequently associated with cerebrovascular risk factors in the elderly, particularly hypertension, and have been interpreted as a subclinical form of ischemic brain damage. WMHI, clinical stroke and blood pressures show significant genetic influences. The objective of this study was to determine whether a relationship exists between family history of stroke and/or hypertension in first degree relatives and WMHI in the elderly. WMHI and stroke (CVA) volumes were quantified from brain MRI performed on 414 white, male twins born between 1917 and 1927 (average age 72.3 +/- 2.9 years). WMHI, adjusted for age and head size, was significantly correlated with the family history score (r = 0.21, p < 0.001). Dividing the family history scores into quintiles revealed significant differences in WMHI by quintile mean (p < 0.05). Subjects in the highest quintile of family history score had the highest mean WMHI. Recalculation of the family history score, by only counting relatives reported to have had a clinical stroke as a positive event, revealed a nonsignificant correlation with WMHI, but the correlation of the family history score with MRI CVA volume was significant (p < 0.05). Stepwise multivariate analysis including ApoE status, current smoking status, smoking packyear history, Doppler ankle/arm blood pressure ratios, current and long term hypertensive status and current systolic and diastolic pressures indicated that the stroke/hypertension family history score was the single best predictor (p < 0.01) of WMHI volumes. Family history was not an independent predictor of CVA volume.
Asymmetry of a-b ridge count, a dermatoglyphic trait in the second interdigital (ID II) palmar area was studied in 314 identical (MZ) twin-pairs of known placental type. Statistically significant differences were observed for the variability of a-b ridge count with respect to placentation. Monochorionic MZ pairs displayed more within-pair variability than dichorionic MZ twins. Within dichorionic pairs, greater variability was observed in MZ twins when pairs with fused placentas were compared with those with separate placentas. A similar pattern of greater variability in dichorionic fused versus dichorionic separate placentas was also found in 121 same sex dizygotic twin-pairs. The pattern of within-pair differences was consistent with a placental proximity effect like that known for the variability in birth weight in twins.
The National Heart, Lung, and Blood Institute Twin Study is a collaborative, longitudinal study of white, male twins who were veterans of World War II and were born between 1917 and 1927. The twins were selected from the National Academy of Sciences/National Research Council Twin Panel and were examined three times (1969-73, 1981-82, and 1986-87). At all three exams, the dizygotic (DZ) twins were found to have a greater total variance for high density lipoprotein cholesterol (HDL-C) than the monozygotic (MZ) twins (p less than 0.05). DZ variance estimates were also larger than the variance of singletons from the second National Health and Nutrition Examination Survey. At the third exam, HDL-C was divided by precipitation into HDL2 and HDL3 fractions, and HDL2 was found to be the primary cause of the greater DZ total variance (DZ/MZ HDL2 variance = 2.22). The DZ/MZ variance ratio decreased 9% after adjustment of HDL2 for correlations with plasma triglycerides, alcohol consumption, smoking, exercise, and body mass index measured at the third exam. Postulated causes of the difference between MZ and DZ total variances include World War II induction screening, environmental influences unique to one zygosity, and genetic factors related to twinning. Further understanding of the etiology of this striking difference between MZ and DZ twin variance for HDL-C fractions could lead to more effective methods of decreasing the complications of arteriosclerosis.
Cardiac hypertrophy and heart failure are known to be associated with a reduction in Ca2+-ATPase pump levels of the sarcoplasmic reticulum (SR). To determine whether, and to what extent, alterations in Ca2+ pump numbers can affect contraction and relaxation parameters of the heart, we have overexpressed the cardiac SR Ca2+-ATPase specifically in the mouse heart using the alpha-myosin heavy chain promoter. Analysis of 2 independent transgenic lines demonstrated that sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA2a) mRNA levels were increased 3.88+/-0. 4-fold and 7.90+/-0.2-fold over those of the control mice. SERCA2a protein levels were increased by 1.31+/-0.05-fold and 1.54+/-0. 05-fold in these lines despite high levels of mRNA, suggesting that complex regulatory mechanisms may determine the SERCA2a pump levels. The maximum velocity of Ca2+ uptake (Vmax) was increased by 37%, demonstrating that increased pump levels result in increased SR Ca2+ uptake function. However, the apparent affinity of the SR Ca2+-ATPase for Ca2+ remains unchanged in transgenic hearts. To evaluate the effects of overexpression of the SR Ca2+ pump on cardiac contractility, we used the isolated perfused work-performing heart model. The transgenic hearts showed significantly higher myocardial contractile function, as indicated by increased maximal rates of pressure development for contraction (+dP/dt) and relaxation (-dP/dt), together with shortening of the normalized time to peak pressure and time to half relaxation. Measurements of intracellular free calcium concentration and contractile force in trabeculae revealed a doubling of Ca2+ transient amplitude, with a concomitant boost in contractility. The present study demonstrates that increases in SERCA2a pump levels can directly enhance contractile function of the heart by increasing SR Ca2+ transport.
Central venous catheters are being used with increasing frequency to administer drugs, and as a result, catheter obstruction caused by precipitation of poorly soluble fluid components has become a common problem. We report our first experience using 0.1 N hydrochloric acid to restore patency to central venous catheters obstructed from insolubility-induced precipitation. Precipitation was caused by drug as well as calcium and phosphorus incompatibilities. The initial use of urokinase in two cases was unsuccessful in restoring catheter patency. In all four cases, the instillation of 0.2-1.0 ml of HCl cleared the catheters. Catheter patency usually was gained immediately. No side effects were noted. Our experience supports preliminary data (JPEN 9 (suppl):255, 1985) which suggest that 0.1 N HCl is effective in clearing insolubility-induced precipitation in central venous catheters.
To determine how much blood must be discarded before one can obtain a reliable central venous catheter blood culture, we prospectively cultured the blood (from 96 patients) that is ordinarily discarded before obtaining blood for such a culture. We then compared the prospective culture results with those of the actual blood culture. Three sequentially drawn aliquots of blood were aspirated from the central venous catheter and cultured. The culture results of the second aliquot were comparable to those of the third (the portion usually cultured) in overall sensitivity (94.4%), specificity (94.9%), and positive predictive value (80.9%). Thus, the amount of blood that must be discarded (infants: 0.3 mL; children: 1.0 mL) before one can obtain an accurate central venous catheter culture is less than was previously thought.
BACKGROUND: Our objective was to compare the accuracy of drug levels in blood samples obtained from central venous catheters with those from peripheral blood samples taken to monitor various drug levels. METHODS: Pediatric patients with central venous catheters receiving aminoglycosides, vancomycin, or cyclosporine had central and peripheral blood samples obtained within 5 minutes of each other and analyzed simultaneously. We ascertained how well blood levels from central venous catheters compared with those from peripheral blood (the criterion standard). RESULTS: There were no clinically significant differences between central and peripheral values for amikacin, gentamicin, tobramycin, and vancomycin (both peaks and troughs). Preliminary data indicated that oral cyclosporine can be monitored via central venous catheter. In contrast, there was poor agreement between peripheral and central values when cyclosporine was administered by IV. CONCLUSIONS: Amikacin, gentamicin, tobramycin, vancomycin, and probably oral cyclosporine can be monitored accurately via central venous catheter. In contrast, IV cyclosporine should be monitored via peripheral blood.
Central venous catheter (CVC) occlusions have the potential of compromising patient care because of the inability to administer needed medications, parenteral nutrition, and blood products. The practitioner responsible for the care of these catheters can be instrumental in the diagnosis and treatment of catheter-related occlusions by becoming familiar with typical complications and their causes. This article describes the causes and possible solutions for some of the most common types of mechanical, thrombus, and precipitate occlusions with the CVC. A discussion of CVC fracture will help the practitioner in the resolution of this complication.