Volume and mortality in coronary artery bypass grafting.
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California↗
Biomedical subjects
J D Parker
Publications and source records attributed to J D Parker.
Functional significance of presynaptic alpha-adrenergic receptors in failing and nonfailing human left ventricle.
BACKGROUND: There are alpha-adrenergic receptors on human myocardium that exert positive inotropic effects. The effect of alpha-adrenergic receptor blockade on human left ventricular (LV) performance has not been fully explored. Although alpha-adrenergic receptor blockade might have effects on LV function that are mediated via blockade of postsynaptic myocardial alpha-adrenergic receptors, it is also possible that blockade of presynaptic alpha 2-adrenergic receptors and subsequent increased release of norepinephrine would have effects on LV performance. In the present study, we explored the effects of nonselective alpha-adrenergic receptor blockade on LV performance and transcardiac norepinephrine concentrations in a group of patients with normal LV function and in a group of patients with congestive heart failure secondary to dilated cardiomyopathy. METHODS AND RESULTS: Using an intracoronary drug infusion technique, we administered the nonselective alpha-adrenergic antagonist phentolamine to 13 patients with normal LV function and 19 patients with congestive heart failure secondary to dilated cardiomyopathy. With a high-fidelity LV catheter, the systolic (+dP/dt) and diastolic (-dP/dt and Tau) LV function responses to intracoronary infusion of phentolamine (0.2 mg/min x 5 minutes) were assessed. In 8 patients with normal ventricular function and 10 patients with congestive heart failure, arterial and coronary sinus blood samples were drawn to determine the effects of phentolamine on catecholamine concentrations. Phentolamine had no measurable effect on LV performance or catecholamine concentrations in the normal ventricular function group. In patients with congestive heart failure, intracoronary phentolamine caused a significant increase in +dP/dt and the rate of isovolumic LV relaxation (-dP/dt and Tau). These hemodynamic effects were accompanied by a significant increase in coronary sinus norepinephrine concentration but no change in arterial norepinephrine concentration. CONCLUSIONS: Myocardial alpha-adrenergic receptor blockade causes significant inotropic and lusitropic effects in the failing but not the nonfailing human LV. These effects appear to be mediated by increased release of norepinephrine from cardiac nerves secondary to blockade of presynaptic alpha 2-adrenergic receptors. Differences in the responses of the failing and nonfailing human LV appear to reflect the higher level of sympathetic activation that is seen in the group with congestive heart failure. This suggests that the presynaptic alpha 2-adrenergic receptor exerts a tonic inhibitory effect on the release of norepinephrine from cardiac nerves in patients with congestive heart failure.
Adrenergic alpha-Antagonists↗
Plaque-associated expression of human herpesvirus 6 in multiple sclerosis.
Representational difference analysis was used to search for pathogens in multiple sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination of 86 brain specimens by PCR demonstrated that HHV-6 was present in > 70% of MS cases and controls and is thus a commensal virus of the human brain. By DNA sequencing, 36/37 viruses from MS cases and controls were typed as HHV-6 variant B group 2. Other herpesviruses, retroviruses, and measles virus were detected infrequently or not at all. HHV-6 expression was examined by immunocytochemistry with monoclonal antibodies against HHV-6 virion protein 101K and DNA binding protein p41. Nuclear staining of oligodendrocytes was observed in MS cases but not in controls, and in MS cases it was observed around plaques more frequently than in uninvolved white matter. MS cases showed prominent cytoplasmic staining of neurons in gray matter adjacent to plaques, although neurons expressing HHV-6 were also found in certain controls. Since destruction of oligodendrocytes is a hallmark of MS, these studies suggest an association of HHV-6 with the etiology or pathogenesis of MS.
Adult↗
Porphyrins in canine and feline dental calculus and Pasteurella multocida cultured from calculus.
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Animals↗
Targeted ablation of pituitary pre-proopiomelanocortin cells by herpes simplex virus-1 thymidine kinase differentially regulates mRNAs encoding the adrenocorticotropin receptor and aldosterone synthase in the mouse adrenal gland.
We have produced and characterized lines of transgenic mice expressing a fusion gene composed of the pituitary expression-specific promoter region of the POMC gene, driving the herpes simplex viral-1 thymidine kinase. Adult mice were treated with the antiherpes agent ganciclovir at 70 mg/kg body weight (ip, twice daily for 10-12 days). Approximately 98% of the pituitary intermediate lobe melanotropes and anterior lobe corticotropes were ablated as determined by immunocytochemistry and RIA specific for the POMC-derived peptides, ACTH, beta-endorophin, and alpha-MSH. The number of lactotropes, somatotropes, thyrotropes, and gonadotropes was not altered compared with controls, indicating that in the adult pituitary, POMC products are not required to maintain the distribution of cell types. As expected, plasma corticosterone levels were substantially decreased after POMC cell ablation. In situ hybridization studies showed that the mouse ACTH receptor was expressed uniformly throughout the adrenal cortex, and RNase protection assays revealed that the ACTH receptor mRNA decreased after pituitary POMC cell ablation. Additionally, RNase protection assays showed that pituitary POMC cell ablation resulted in the decrease of adrenal p450c11 beta transcripts while p450c11AS (aldosterone synthase) mRNA levels remained constant. These data demonstrate differential regulation of steroid pathway-specific enzymes by POMC products. Our results also suggest that the thymidine kinase cell obliteration technique may not be dependent on cell division as a prerequisite for cytotoxicity, thus supporting the idea that targeted molecular ablation using cell- and tissue-specific promoter sequences to drive viral thymidine kinase expression can be refined further to study other nonmitotic cells.
Adrenal Cortex↗
Neurohormonal activation during nitrate therapy: a possible mechanism for tolerance.
The hemodynamic and antianginal effects of the organic nitrates are greatly reduced during therapy designed to provide 24-hour protection throughout each day. Although the mechanisms of tolerance are not clearly understood, it is likely that tolerance is related to a combination of reduced sulfhydryl groups in vascular smooth muscle and neurohormonal activation. These changes would reduce nitrate-induced vasodilation and induce sodium and water retention with an increase in plasma volume. These reflex neurohormonal changes would reduce the hemodynamic effect of any given degree of nitrate-induced vasodilation. Although preliminary studies suggest that diuretic therapy or the use of converting enzyme inhibitors may reduce or abolish tolerance, further clinical studies are required to confirm these findings.
Angiotensin-Converting Enzyme Inhibitors↗
Influence of paternal characteristics on the risk of low birth weight.
The combined effects of maternal and paternal factors on the risk of delivering low birth weight (less than 2,500 g) and very low birth weight (less than 1,500 g) infants were examined among married parents. Using 1984-1988 natality data compiled by the National Center for Health Statistics, the authors found paternal education and race to have independent effects on the risks of low birth weight and very low birth weight after adjustment for maternal characteristics. The odds of low and very low birth weight decreased with increasing paternal education. Adjustment for paternal education decreased the effect of maternal education on the risks of low and very low birth weight. Additionally, the examination of paternal race led to the identification of a subgroup of married black women with lower risks of low and very low birth weight than married black mothers overall. These data suggest that paternal characteristics should be used, in addition to maternal characteristics, to describe the risks of low and very low birth weight.
Adult↗
Estimation of mitral valve area from regression analysis of the pressure gradient in mitral stenosis.
Estimation of mitral valve area (MVA) in the cardiac catheterization laboratory is prone to pitfalls because of the time required for calculations and inaccuracies in the measurement of cardiac output. Because the rate of decrease in the mitral gradient directly correlates with the severity of mitral stenosis, an on-line estimate of MVA at the time of catheterization may be possible with regression analysis of digitized pressure recordings. A total of 61 comparisons of mitral gradient measurements and MVA were obtained in 37 patients at diagnostic catheterization and in 24 patients after balloon mitral valvotomy. Linear and nonlinear regression parameters yielded pressure half-time values and empiric constants similar to those used in Doppler echocardiography for estimation of MVA. The correlations derived from linear analysis were as good as those obtained from nonlinear analysis: from linear analysis, MVAregression = 0.79.MVAGorlin -0.03; r2 = 0.64, p = 0.0001; and from double exponential analysis, MVAregression = 0.86.MVAGorlin -0.07; r2 = 0.74; p = 0.0001. The correlations were not significantly affected by the presence of mild to moderate mitral regurgitation or whether they were obtained after balloon valvotomy. In summary, linear regression analysis yields accurate estimates of MVA despite the theoretical superiority of nonlinear methods. On-line digital analysis of mitral gradient tracings may thus be useful at the time of diagnostic cardiac catheterization or balloon mitral valvotomy to assess the severity of mitral stenosis and the response to interventions.
Aged↗
Alexithymia and somatic complaints in psychiatric out-patients.
This study investigated the prevalence of alexithymia and its relationship with somatic complaints in a sample of 118 general psychiatric out-patients. Of the sample 39.8% scored in the alexithymic range of the Toronto Alexithymia Scale. Compared with the non-alexithymic patients, the alexithymic patients scored significantly higher on several Minnesota Multiphasic Personality Inventory (MMPI) scales that collectively measure a diverse and extensive range of somatic symptoms and bodily concerns. In addition, the alexithymic patients had significantly higher levels of anxiety, depression, and general psychological turmoil. Although the alexithymic and non-alexithymic patients did not differ on the MMPI Repression and overall Hysteria Scales, which reflect the defenses of denial and repression, the alexithymic patients had significantly less ego strength and were significantly more dependent and more likely to engage in impulsive and acting out behaviours. The overall pattern of results is consistent with the view that alexithymic individuals are prone to both 'functional' somatic symptoms and symptoms of emotional turmoil because they are not well equipped psychologically.
Adult↗
Effects of diuretic therapy on the development of tolerance during continuous therapy with nitroglycerin.
OBJECTIVES: This study examined the effects of concurrent diuretic therapy on the hemodynamic responses to short-term and sustained therapy with transdermal nitroglycerin. BACKGROUND: Sodium retention and plasma volume expansion occur during therapy with nitroglycerin and may play a role in the loss of nitroglycerin effects during sustained therapy. METHODS: Twenty-two normal male volunteers were treated for 1 week with either hydrochlorothiazide and amiloride (50 + 5 mg) (n = 11) or placebo (n = 11) in a randomized, double-blind fashion. All 22 subjects then received continuous transdermal nitroglycerin (19 +/- 1 mg/24 h) for 5 to 7 days. RESULTS: On the first and last day of transdermal nitroglycerin therapy, standing heart rate, systolic blood pressure and hematocrit values were assessed at 8, 9 and 10 AM and 12 noon. Heart rate and blood pressure responses to sublingual nitroglycerin (0.6 mg) were also evaluated before and after sustained transdermal nitroglycerin therapy. A significant loss of the hemodynamic effects of transdermal and sublingual nitroglycerin occurred during sustained therapy in both the diuretic and placebo therapy groups. In both groups, transdermal nitroglycerin therapy was associated with a significant decrease in hematocrit that persisted for the entire treatment period. CONCLUSIONS: These results suggest that diuretic therapy does not prevent plasma volume expansion or the loss of hemodynamic effects during sustained transdermal nitroglycerin therapy. The persistent decrease in hematocrit suggests that plasma volume expansion plays a role in the attenuation of nitrate effects. It also provides evidence of continued vascular activity of nitroglycerin despite loss of systemic hemodynamic effects.
Administration, Cutaneous↗
Serial assessment of left ventricular function and mass after orthotopic heart transplantation: a 4-year longitudinal study.
Long-term changes in left ventricular performance and geometry in the transplanted human heart have been incompletely described. Therefore, two-dimensional echocardiograms were performed on 22 recipients of an orthotopic heart transplant at 1 month (32 +/- 20 days), 1 year (11 +/- 3 months) and 4 years (54 +/- 9 months) after transplantation. All studies were performed at a time when the patient had no pathologic evidence of rejection. Ten healthy men served as a normal control group. Over 4 years of follow-up, mean systolic blood pressure in the study patients increased from 121 +/- 12 (p = NS vs. values in the control group) to 139 +/- 11 mm Hg (p less than 0.05 vs. both control values and values at 1 month); mean diastolic blood pressure increased from 72 +/- 7 (p = NS vs. normal values in the control group) to 93 +/- 8 mm Hg (p less than 0.05 vs. both control values and values at 1 month). Left ventricular end-systolic volume increased from 42 +/- 10 (p = NS vs. control values) to 51 +/- 14 ml (p less than 0.05 vs. both control values and values at 1 month) and end-diastolic volume increased from 103 +/- 28 (p = NS vs. control values) to 112 +/- 27 ml (p less than 0.05 vs. control values) over 4 years. Left ventricular mass and ejection fraction did not change significantly within the patient cohort and remained similar to that found in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure↗
Evolution of the salmonid mitochondrial control region.
To explore the evolutionary nature of the salmonid mitochondrial DNA (mtDNA) control region (D-loop) and its utility for inferring phylogenies, the entire region was sequenced from all eight species of anadromous Pacific salmon, genus Oncorhynchus; the Atlantic salmon, Salmo salar; and the Arctic grayling, Thymallus arcticus. A comparison of aligned sequences demonstrates that the generally conserved sequence elements that have been previously reported for other vertebrates are maintained in these primitive teleost fishes. Results reveal a significantly nonrandom distribution of nucleotide substitutions, insertions, and deletions that suggests that portions of the salmonid D-loop may be under differential selective constraints and that most of the control region of these fishes may evolve at a rate similar to that of the remainder of their mtDNA genomes. Maximum likelihood and Fitch parsimony analyses of 9 kb of aligned salmonid sequence data give evolutionary trees of identical topology. These results are consistent with previous molecular studies of a limited number of salmonid taxa and with more comprehensive, classical analyses of salmonid evolution. Predictions from these data, based on a molecular clock assumption for the mtDNA control region, are also consistent with fossil evidence that suggests that species of Oncorhynchus could be as old as the Middle Pliocene and would have thus given rise to the extant Pacific salmon prior to about 5 or 6 million years ago.
Animals↗
Self-reports of depression and state-trait anxiety: evidence for differential assessment.
Several researchers have found anxiety and depression to be indistinguishable in nonclinical samples and have suggested that both constructs may be components of a general psychological distress process. Another possibility is that overlap is due to the psychometric limitations of scales used. A series of exploratory factor analyses were conducted in a nonclinical sample (N = 605) using the Beck Depression Inventory (BDI; Beck, 1978), the State-Trait Anxiety Inventory (STAI; Spielberger, 1983), and the Endler Multidimensional Anxiety Scales (EMAS; Endler, Edwards, & Vitelli, 1991). Both state and trait anxiety and depression could be differentiated with the BDI and the EMAS but not with the STAI. Some theoretical models of negative affectivity or general psychopathology may be premature.
Adult↗
The Revised Toronto Alexithymia Scale: some reliability, validity, and normative data.
Addressing certain problems with the compositional structure of the self-report Toronto Alexithymia Scale, this paper reports the development of a revised version of the scale as well as results from a preliminary series of studies evaluating its reliability and validity. The Revised Toronto Alexithymia Scale (TAS-R) demonstrated good internal consistency and a stable and replicable two-factor structure that is congruent with the two major dimensions of the alexithymia construct. Evidence of convergent and discriminant validity for the TAS-R was provided by correlations with measures of other constructs. Criterion validity was demonstrated by the ability of TAS-R scores to discriminate between behavioral medicine outpatients designated alexithymic and those designated non-alexithymic on the basis of clinical interview ratings. Normative data are provided for university student, normal adult, and psychiatric outpatient populations.
Adult↗
Relationship between conjugate lateral eye movements and alexithymia.
The relationship between conjugate lateral eye movements (CLEMs) and alexithymia was investigated in a group of 60 (23 male and 37 female) right-handed university students. Subjects completed the Toronto Alexithymia Scale (TAS), the Schalling-Sifneos Personality Scale, and the Basic Personality Inventory, which measures 12 basic dimensions of personality and psychopathology, CLEMs were recorded while subjects were asked 20 general knowledge questions that have no tendency to elicit eye movements predominantly in one direction. A series of gender by CLEM preference (left vs. right mover) ANOVAs were conducted with the various measures. There was a significant relationship between right CLEM preference and higher scores on the TAS, but no relationships between CLEMs and any of the other measures. These results suggest that alexithymia is associated with left cerebral lateralization, and support the hypothesis that alexithymic characteristics reflect a variation in brain organization.
Adult↗
Alexithymia in women with anorexia nervosa. A preliminary investigation.
The prevalence of alexithymia in 48 female anorexia nervosa patients was 77.1% compared with a prevalence of 6.7% in 30 normal female subjects, matched by age and education. Alexithymia correlated negatively with education in the anorexic patient group, but was unrelated to duration of illness, amount of weight loss, and levels of depression and of general psychoneurotic pathology.
Adult↗
Prenatal weight gain advice: an examination of the recent prenatal weight gain recommendations of the Institute of Medicine.
The Institute of Medicine (IOM) recently published new guidelines for maternal weight gain during pregnancy. Using data collected at Moffitt Hospital, University of California at San Francisco, we examined the associations between maternal weight gain outside the recommendations of the IOM and three pregnancy outcomes (small for gestational age [SGA] infants, large for gestational age [LGA] infants, and cesarean delivery). These analyses were repeated using population-specific weight gain ranges derived from a subgroup of women in this cohort with healthy pregnancy outcomes. The purpose of the study was to compare the national guidelines of the IOM with hospital standards. Both the recommendations of the IOM and the hospital ranges were associated with fewer SGA infants, LGA infants, and cesarean deliveries. The overall associations were similar for the population-derived and national ranges. Although the IOM ranges should be examined in other populations and with other birth outcomes, our results validated their recommendations. Maternal weight gain within the IOM recommendations reduced the risk of the outcomes studied; furthermore, these ranges performed as well as those derived from the target population.
Birth Weight↗
Artificial mutants generated by the insertion of random oligonucleotides into the putative nucleoside binding site of the HSV-1 thymidine kinase gene.
We have obtained 42 active artificial mutants of HSV-1 thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) by replacing codons 166 and 167 with random nucleotide sequences. Codons 166 and 167 are within the putative nucleoside binding site in the HSV-1 tk gene. The spectrum of active mutations indicates that neither Ile166 nor Ala167 is absolutely required for thymidine kinase activity. Each of these amino acids can be replaced by some but not all of the 19 other amino acids. The active mutants can be classified as high activity or low activity on two bases: (1) growth of Escherichia coli KY895 (a strain lacking thymidine kinase activity) in the presence of thymidine and (2) uptake of thymidine by this strain, when harboring plasmids with the random insertions. E. coli KY895 harboring high-activity plasmids or wild-type plasmids can grow in the presence of low amounts of thymidine (less than 1 microgram/mL), but are unable to grow in the presence of high amounts of thymidine. On the other hand, E. coli KY895 harboring low-activity plasmids can grow at a high concentration of thymidine (greater than 50 microgram/mL) in the media. The high-activity plasmids also have an enhanced [3H]dT uptake. The amounts of thymidine kinase activity in vitro in unfractionated extracts do not correlate with either growth at low thymidine concentration or the rate of thymidine uptake. Heat inactivation studies indicate that the mutant enzymes are without exception more temperature-sensitive than the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗