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Biomedical subjects

J M Sullivan

Publications and source records attributed to J M Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Practical aspects of preventing and managing athersclerotic disease in post-menopausal women.

Factors that exacerbate the risk of atherosclerotic plaque formation include cigarette smoking, hypertension, hypercholesterolaemia, sedentary lifestyle, and oestrogen deficiency. The potentially important role of oestrogen deficiency in this process is evidenced by the significant increase in cardiovascular risk observed in women after menopause, and in the marked reduction in cardiovascular events observed in women who take hormone replacement therapy. Oestrogen replacement therapy, through an effect on the blood vessel wall and on serum lipids, also appears to stabilize existing atherosclerotic plaques. The combination of oestrogen and progesterone reduces risk of endometrial cancer while possibly delivering the same benefits as oestrogen alone. Other measures, such as antithrombotic therapy, exercise, and smoking cessation, also contribute to reduced risk of cardiovascular disease in older women.

Coronary Artery Disease↗
PubMed1996

A 1996 update on antihypertensive agents.

Seven new classes of antihypertensive agents that are currently under development are outlined. Clinical studies of neutral endopeptidase inhibitors and angiotensin II receptor blockers are described. Experimental studies are described involving endothelin inhibitors, and clinical and experimental studies of a new multiple action antihypertensive agent, carvedilol, are presented. Studies demonstrating the efficacy of very low doses of thiazide diuretics added to other antihypertensive agents are described. A meta-analysis that found increased risk of sudden death in hypertensive patients treated with non-potassium-sparing diuretics is reported. The controversy over the use of calcium-channel blockers is reviewed, and current recommendations regarding the use of rapidly-acting nifedipine are given.

Angiotensin Receptor Antagonists↗
PubMed1996

Hemodynamic effects of aerobic vs resistance exercise.

Previous studies suggest that aerobic exercise lowers blood pressure (BP), while isometric exercise increases BP, at least transiently. The purpose of this study was to examine the hemodynamic effect of a 6-week training period of aerobic exercise or weight training. Twenty deconditioned healthy males ages 18-36, self-selected a training regimen. The aerobic group exercised 30 min/day, 4 times each week to achieve 60-80% maximal heart rate. The resistance group lifted weights at 65-80% maximal voluntary contraction; 3-4 sets of 8-12 repetitions; 3 day/week using large muscle groups. Hemodynamic measurements of heart rate, BP, venous capacitance, forearm blood flow, and vascular resistance were made at baseline and week 6 by plethysmography and analyzed by 2-way ANOVA. The groups showed no differences in baseline characteristics. A training effect was confirmed by a decrease in resting heart rate in the aerobic group (71.5 +/- 4.4 to 64.5 +/- 3.7, beats per minute, P = 0.004), and an increase in total work capacity in the weight lifting group (6231 vs 7508, P = 0.01). Forearm blood flow increased similarly in both groups, averaging 17% (3.5 +/- 0.2 vs 4.2 +/- 0.2 ml 100 g/min, P = 0.03), while forearm vascular resistance fell 19% (28.8 +/- 1.7 vs 24.3 +/- 1.7 mm Hg/ml/min 100 g, P = 0.08). The main differences between the groups after training was found in their response to isometric stress (1/3 maximal handgrip). The weight-lifting group had a greater increase of forearm blood flow and venous capacitance, less increase in systolic BP (SBP) and a greater fall of forearm vascular resistance, (P < 0.05) while the aerobic group had less increase in SBP and heart rate (P < 0.04) but no significant change of forearm hemodynamics. We conclude that both aerobic and repetitive weight programs have short term favorable effects on resting forearm BP and resistance. The exercise programs differ in altering the individual's physiologic response to subsequent isometric stress. However, exercise training of longer duration or greater intensity or frequency could alter these results.

Adult↗
PubMed1995

Three distinct structural environments of a transmembrane domain in the inwardly rectifying potassium channel ROMK1 defined by perturbation.

To probe the protein environment of an ion channel, we have perturbed the structure of a transmembrane domain by substituting side chains with those of two different sizes by using site-specific mutagenesis. We have used Trp and Ala as a high- and a low-impact perturbation probe, respectively, to replace each of 18 consecutive residues within the putative second transmembrane segment, M2, of an inwardly rectifying potassium channel, ROMK1. Our rationale is that a change in the channel function as a consequence of these mutations at a particular position will reflect the structural environment of the altered side chain. Each position can then be assigned to one of three classes of environments, as grated by different levels of perturbation: very tolerant (channel functions with both Trp and Ala substitutions), tolerant (function preserved with Ala but not with Trp substitution), and intolerant (either Ala or Trp substitution destroys function). We identify the very tolerant environment as being lipid-facing, tolerant as protein-interior-facing, and intolerant as pore-facing. We observe a strikingly ordered pattern of perturbation of all three environmental classes. This result indicates that M2 is a straight alpha-helix.

Alanine↗
PubMed1995

Impact of patency of the left anterior descending coronary artery on long-term survival.

This study examines the relative importance of patency of the left anterior descending (LAD) coronary artery on long-term survival when the LAD is the only significantly narrowed coronary artery. From a cardiac disease registry of 21,786 patients, 826 medically treated patients with isolated LAD disease were identified. These patients were followed for > 5 years. Patients were divided into those with open versus those with closed arteries. With the use of univariate and multivariate analysis, the relative importance of the patency of the LAD was determined. All patients with previous anterior wall infarction were analyzed as a separate group, and those with and without a patent LAD were compared. Overall, survival was significantly better in patients with an open LAD. However, multivariate analysis of either the entire study group or the group with myocardial infarction showed that coronary artery patency was not an independent predictor of long-term survival. Analysis of patients with prior anterior myocardial infarction showed significantly improved 5-year survival in younger patients (< 70 years) who had an open (but stenosed) versus a closed LAD without angiographic collateral formation (94% vs 81%, p = 0.025). Furthermore, this survival difference was most striking in patients with left ventricular dysfunction. Survival in younger patients with an open LAD was similar to that of patients with a closed LAD with collateral formation (94% vs 92%, p = 0.55). No differences in survival were observed in the groups without infarction. This study implies that an open LAD improves long-term survival for younger patients with a previous anterior myocardial infarction and no collateral support to the ischemic or infarcted myocardium.

Coronary Disease↗
PubMed1995

In situ human obstetrical ultrasound exposimetry: estimates of derating factors for each of three different tissue models.

A specialized in vivo exposimetry system was developed to acquire transabdominal in situ ultrasound exposure quantities in obstetric patients. Under surgical conditions, the sterilized 7-element calibrated linear array hydrophone was introduced into the uterus under direct ultrasound guidance and placed in direct contact with the products of conception, usually in the saggital midplane of the uterine cavity. Twenty-five patients with empty bladders and 10 patients with full bladders were studied at gestational ages between 7 and 20 weeks. In the empty bladder condition, the sound beam traversed the anterior abdominal wall, uterus, amniotic fluid and fetal parts and in the full bladder condition, the sound beam also traversed the fluid-filled bladder. Each study was conducted with a 3 MHz, mechanical sector transducer in combination with an ATL Ultramark 4 diagnostic ultrasound imaging system. Calibration data were recorded after completion of each in vivo patient study. The acquired exposimetry data from the 35 obstetric patients were used to evaluate the appropriateness of three tissue attenuation models, viz., fixed path, homogeneous and overlying. All three tissue models yield a mean attenuation coefficient value of about a factor of 3 to 4 greater than their respective minimum values. In the case of the overlying and homogeneous tissue models, there was a statistically significant correlation between their calculated attenuation coefficients and total distance for the combined data set whereas there was no such dependency for the calculated fixed-path tissue model. In summary, any one of the three tissue models may be used to estimate in utero acoustic quantities during the first and second trimesters of human pregnancy based on this study.

Adult↗
PubMed1995

The effect of noncritical coronary artery disease on long-term survival.

This study was designed to determine the impact of noncritical (less than 70% narrowing of the luminal diameter) coronary stenoses on the long-term survival rate of patients with coronary artery disease. The survival rate of 3,342 patients with normal coronary arteries (Group 1A) was compared with that of 2,184 patients with only noncritical stenoses (Group 1B). Similarly, the survival rate of 1,128 patients with one or more critical lesions (Group 2A) was compared with that of 5,944 cases with noncritical plus critical lesions (Group 2B). Patients with noncritical lesions had significantly lower 10-year survival rates (85.8%) than did those with normal coronary arteries (90.1%). However, the difference in survival rate was attributable to older age, male sex, and higher prevalence of cigarette smoking, diabetes mellitus, and hypertension in Group 1B than in Group 1A; presence of noncritical stenoses was not a statistically significant independent determinant of survival. Long-term survival rates of the patients with one or more critical lesions (Group 2A) were equivalent to that of patients with critical stenoses plus one or more noncritical lesions (Group 2B). Therefore, 1) patients with only noncritical stenoses have more risk factors for coronary artery disease than do those with normal coronary arteries; 2) these patients have a reduced long-term survival rate that reflects these risk factors rather than the presence of noncritical lesions; and 3) in patients with critical lesions, the presence of additional non-critical stenoses does not affect the long-term survival rate.

Adult↗
PubMed1995

Long-term survival of patients with coronary artery disease during the 1970s. A cohort study.

STUDY OBJECTIVE: This study was undertaken to determine the effects of altered risk factors and treatment modalities on the short- and long-term survival of patients with documented coronary artery disease whose conditions were diagnosed from 1972 through 1982. STUDY DESIGN: The study was a retrospective database analysis of clinical, angiographic, and follow-up information. SETTING: Data from all patients referred for cardiac catheterization at the Baptist Memorial Hospital, Memphis, Tenn, were studied. PATIENTS: Risk factors and survival of patients who underwent cardiac catheterization from 1972 through 1982 and who were followed up for at least 5 years were evaluated. Cohort A included 1,821 patients studied from 1972 through 1977; cohort B included 5,369 patients studied between 1977 and the end of 1982. Each cohort was subdivided based on type of therapy (medical or surgical) that the patients received. MEASUREMENTS AND RESULTS: The 30-day (short-term) and 5-year (long-term) survival rates were compared by life table methods. Short-term survival improved significantly in both medical (from 94.9% to 97.5%, p < 0.001) and surgical (from 95.5% to 97.6%, p < 0.001) groups from cohort A to cohort B. Long-term survival, however, did not differ significantly between the two cohorts. In the medical group, 5-year survival in cohort A was 86.3% and in cohort B it was 86.9% (p = NS); in the surgical group, cohort A it was 89.1% while in cohort B it was 89.4% (p = NS). Prevalence of both cigarette smoking and hypercholesterolemia declined significantly from cohort A to cohort B in both surgical and medical groups. However, advanced age, female gender, and previous myocardial infarction were significantly more common in cohort B than in cohort A for both treatment groups. CONCLUSIONS: These results indicate that during the study period, a significant decline in short-term mortality occurred for patients with angiographically documented coronary artery disease. Long-term survival did not, however, improve possibly due to a complex interplay between factors that promote coronary artery disease, eg, cigarette abuse and hypercholesterolemia, and factors that determine survival, eg, increase in age and history of prior infarction and advances in medical and surgical therapy.

Aged↗
PubMed1995

Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family.

Ionotropic glutamate receptors are composed of homomeric or heteromeric configurations of glutamate receptor subunits. We have cloned a member of a novel class of the rat ionotropic glutamate receptor family, termed chi-1. This subunit exhibits an average identity of 27% to NMDA subunits and 23% to non-NMDA subunits. Regional transcript levels of chi-1 are elevated just prior to and during the first postnatal week, with the highest levels present in the spinal cord, brainstem, hypothalamus, thalamus, CA1 field of the hippocampus, and amygdala. The spatial distribution of chi-1 expression is similar from postnatal day 1 (P1) to adulthood. However, transcript levels decline sharply between P7 and P14 and remain attenuated into adulthood. Functional expression studies in Xenopus oocytes injected with in vitro transcribed chi-1 RNA did not demonstrate agonist-activated currents. Pairwise expression of chi-1 with members of the AMPA, KA, or delta class of glutamate recepto subunits either failed to generate agonist-activated currents or failed to alter the underlying current generated by the coexpressed subunit. However, coexpression of chi-1 with subunits forming otherwise functional NMDA receptors resulted in an inhibition of current responses. Since chi-1 did not alter the currents generated by non-NMDA subunits, this suggests that chi-1 may specifically interact with NMDA receptor subunits. Further characterization will be required to establish the precise role of this glutamate receptor subunit in neuronal signaling.

Aging↗
PubMed1994

Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor.

Modulation of NMDA-mediated responses by oxidizing and reducing reagents has been described in a variety of neuronal preparations. Here, we report that NMDA-gated currents of oocytes expressing heteromeric NMDA receptors are also modulated by sulfhydryl redox reagents. Each cysteine residue in the NMDAR1 (NR1) subunit and each conserved NMDAR2 (NR2) cysteine residue in a prototypical subunit (NR2B) was tested for its role in redox modulation. We have identified 2 cysteines in the NR1 subunit that are required for redox modulation of NMDA-gated currents in oocytes expressing NR1-NR2B, NR1-NR2C, or NR1-NR2D receptors. Mutation of these same 2 cysteines also eliminated potentiation by spermine and shifted the IC50 for H+ inhibition and the EC50 for NMDA. Redox modulation of heteromeric NR1-NR2A receptors appeared to be different from that of the other heteromeric receptors, indicating the presence of one or more unique redox modulatory sites on NR1-NR2A receptors.

Animals↗
PubMed1994

Clinical practice guidelines: implications for use.

The differences between standards and clinical practice guidelines are discussed. Implications for using guidelines in nursing practice in defining scope of practice, evaluating careless or negligent practice, practicing outside of clinical guidelines, and using clinical guidelines for cost containment are presented.

Clinical Protocols↗
PubMed1994

Care provided by a nurse managed center: polyarteritis nodosa.

Polyarteritis nodosa is a form of necrotizing vasculitis involving small and medium size arteries. Nursing care provided by baccalaureate nursing students in a nurse-managed center at San Jose State University's (CA) School of Nursing focuses on monitoring symptoms, preventing complications, and supporting patients and families affected by polyarteritis nodosa.

Aged↗
PubMed1994

Atherosclerosis and estrogen replacement therapy.

Cardiovascular morbidity and mortality increase after menopause. There has been reluctance to use estrogen replacement therapy (ERT) for treating women with a high risk of cardiovascular disease because of adverse experience in two areas: (1) The Coronary Drug Project administered high doses of estrogen to male survivors of MI, which was associated with excess coronary and thromboembolic events. (2) Studies of OC use revealed an increased incidence of heart attacks among women over the age of 35 years who smoke. Eight case-control studies have examined the effect of estrogen replacement therapy on cardiovascular events; five have shown a protective effect. Eleven of 19 reports have found a protective effect. Ten of 11 cohort studies have found a protective effect. One randomized study (by Nachtigall et al) found a beneficial effect. Angiographic studies at the University of Tennessee/Baptist Memorial Hospital, Memphis have examined the relative risk for coronary artery disease for postmenopausal women relative to estrogen use. Cases with significant coronary angiograms. Logistic regression analysis showed that estrogen use had a statistically significant independent protective effect against coronary atherosclerosis. These observations have been confirmed by three subsequent studies. The same study group also examined the effect of estrogen replacement on survival of patients who underwent coronary arteriography at baseline. Of 23,190 patients undergoing arteriography, 2,268 women were eligible for long-term study. While patients who were initially free of coronary artery lesions did not have a significant reduction of mortality when given estrogen replacement, a significant reduction of all-cause mortality was observed in those groups with coronary artery disease who received estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1993

Protein chemical characterization and immunocytochemical localization of the NMDA receptor subunit NMDA R1.

In the rat central nervous system, the mRNA encoding the N-methyl-D-aspartate receptor subunit R1 is the most ubiquitously distributed among the cloned subunit mRNAs of this glutamate receptor subtype. The N-methyl-D-aspartate R1 mRNA is very abundantly expressed and N-methyl-D-aspartate R1 coexpression is necessary for functional expression of all other cloned N-methyl-D-aspartate receptor subunits. Therefore, the R1 subunit is likely to be an essential component of all known N-methyl-D-aspartate receptors in rat brain. By employing sequence specific polyclonal antibodies, we demonstrate that rat brain N-methyl-D-aspartate R1, as well as recombinantly expressed receptor protein, has an apparent molecular mass of 116 kDa in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The receptor protein is heavily glycosylated. It is specifically localized to the central nervous system, and it co-enriches with synaptic membranes upon subcellular fractionation of the cerebral cortex. Chemical cross-linking of synaptic membrane proteins shows that the N-methyl-D-aspartate R1 protein is part of a receptor protein complex with a molecular mass of 730 kDa. By using immunocytochemical methods, we demonstrate a widespread but distinct distribution of N-methyl-D-aspartate R1 in neurons of the rat brain, with prominent immunostaining in certain layers of the cerebral cortex, in the hippocampus and dentate gyrus, as well as in the cerebellum.

Animals↗
PubMed1993

Voltage- and time-dependent potassium conductances enhance the frequency response of horizontal cells in the turtle retina.

The contribution of voltage- and time-dependent potassium conductances to visual information processing in the distal turtle retina was studied in the isolated retina preparation. The effects of specific potassium channel blockers; tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the membrane potential and photoresponses of L-cones and L-type horizontal cells were monitored with intracellular microelectrodes. Both drugs produced a large depolarization of the L-type horizontal cells though the effect of 4-AP was more transient than that of TEA. While TEA produced response augmentation associated with negligible changes in the kinetics of the photoresponses, 4-AP induced profound changes in response kinetics which were seen as an overshoot of the resting potential at stimulus offset and a pronounced slowing down in the return of the membrane potential toward the prestimulus level. The effects of TEA on horizontal cells could be accounted for by the action of the drug on cone photoreceptors. The effects of 4-AP on the horizontal cells could not be attributed to an indirect action mediated by either the cone photoreceptors or by GABAergic and/or glycinergic neurons in the inner retina. These results suggest that voltage- and time-dependent potassium conductances act to speed up the recovery of the turtle horizontal cell membrane potential from the effects of bright light stimuli. Such a role was supported by the effects of potassium channel blockers on the frequency response curves of horizontal cells: the corner frequency was reduced on the average by 25%.

4-Aminopyridine↗