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Biomedical subjects

J Sullivan

Publications and source records attributed to J Sullivan.

At least 91 records · Page 5Linked to original sources

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared to hydrochlorothiazide.

OBJECTIVE: To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, hydrochlorothiazide (HCTZ). METHODS: In this double-blind study, 167 adult out-patients with mild-to-moderate essential hypertension were randomly allocated in equal number to receive valsartan 80 mg or HCTZ 25 mg for 12 weeks. In patients whose blood pressure (BP) remained uncontrolled after 8 weeks of monotherapy, atenolol 50 mg was added to the initial treatment. Patients were assessed at 4, 8 and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic BP (SDBP) at 8 weeks. Secondary variables included change in sitting systolic BP (SSBP) and responder rates (percentage of patients with SDBP < 90 mmHg or drop > or = 10 mmHg compared to baseline) at 8 weeks. RESULTS: Valsartan and HCTZ were both effective at lowering diastolic and systolic blood pressure at all time points. Similar falls were seen in both groups with no significant differences between treatments. For the primary variable (decrease in SDBP) there was no significant difference between treatments. For SSBP there was also no significant difference observed. Responder rates at 8 weeks were 74% for valsartan and 62% for HCTZ (P = 0.10). Both treatments were well tolerated, both as monotherapy, and when combined with atenolol 50 mg per day. CONCLUSION: The data show valsartan 80 mg to be as effective as HCTZ in the treatment of mild-to-moderate hypertension. The results also show valsartan to be well tolerated when taken alone or in combination with atenolol.

Adolescent↗

Phylogeography and molecular systematics of the Peromyscus aztecus species group (Rodentia: Muridae) inferred using parsimony and likelihood.

Mice of the Peromyscus aztecus species group occur at mid to high elevations in several mountain ranges in the highlands of Middle America (Mexico and Central America), a region of high endemicity. We examined the biogeography of this group by conducting phylogenetic analyses of 668 bp of the mitochondrial cytochrome b (cyt b) gene. Phylogenetic analyses under both parsimony and likelihood frameworks produced the same topologies, but estimates of nodal support were artificially high in weighted parsimony analyses. This difference is attributed to the inability of parsimony to optimize branch lengths when evaluating topologies. These data indicate that the P. aztecus-like populations from south and east of the Isthmus of Tehuantepec currently assigned to P. a. oaxacensis represent a distinct species, with genetic distances as high as 0.091. In addition, P. hylocetes is strongly divergent from Mexican populations of P. aztecus (genetic distances of 0.044-0.069), supporting the recognition of this taxon as a distinct species. The history of divergence in this group can be explained by a series of apparently early to middle Pleistocene vicariance events associated with glacial cycles. The Sierra Madre Occidental and Cordillera Transvolcanica each appear to be faunistically isolated, the Isthmus of Tehuantepec appears to have been a strong Pleistocene barrier, and the Sierra Madre Oriental has affinities with the Sierra Madre del Sur and the highlands of central Oaxaca.

Animals↗

Light versus heavy sedation after cardiac surgery: myocardial ischemia and the stress response. Maritime Heart Centre and Dalhousie University.

UNLABELLED: The influence of light versus heavy sedation after coronary artery bypass graft (CABG) surgery on the development of postoperative myocardial ischemia has not been described. After uncomplicated CABG surgery, 50 patients were randomly assigned to receive LOW (n = 24; target Ramsay Sedation Score [RSS] = 2) or HIGH (n = 26; target RSS = 4) sedation with propofol. Analgesia was provided to maintain a visual analog scale (VAS) pain score <7. Myocardial ischemia was identified perioperatively using continuous 3-lead Holter monitoring. By measuring creatine kinase (CK) MB levels preoperatively, at entry to the intensive care unit (ICU), and every 12 h for 48 h; and by obtaining serial 12-lead electrocardiograms (ECG) (preoperatively; 2, 4, 12, 24, and 48 h after ICU admission, 8:00 AM the morning after surgery; and 5 min pre- and postextubation), myocardial infarction was identified. Endocrine stress response was assessed by measuring serum cortisol levels preoperatively, on admission to the ICU, and 24 h postoperatively. In a subset of patients (LOW n = 10, HIGH n = 11), plasma and urinary catecholamine levels were also measured. There were no between-group differences in demographics, operative course, hemodynamic variables, or cortisol levels while in the ICU. The VAS pain score and target RSS were achieved and sustained, and they differed between groups. There were three myocardial infarctions in each group by CKMB criteria alone. No ECG-identifiable myocardial infarction occurred. The ST segment versus time curve (LOW 187 +/- 295 versus HIGH 1071 +/- 2137 mm/min) differed between groups. Urinary and plasma catecholamine levels were similar between groups over the observation period. We conclude that the use of a reduced sedation regimen in combination with adequate analgesia did not result in an increased endocrine stress response or risk of myocardial ischemia. IMPLICATIONS: This randomized study of patients after coronary artery bypass surgery examined whether light (versus heavy) sedation with propofol in the intensive care unit was associated with an increased degree of myocardial ischemia. Using techniques to detect myocardial ischemia, including Holter monitoring, electrocardiogram, and myocardial enzyme measurements, no differences were found. We conclude that light sedation does not increase the endocrine stress response or the risk of myocardial infarction.

Aged↗

Reducing costs and improving processes for the interventional cardiology patient.

The cardiology unit at the University of Chicago Hospitals developed a cost-saving mechanism in the care of postinterventional cardiology patients, reducing time spent in the coronary care unit. Increased nursing education and training and better identification of patient outcomes made this collaborative effort a cost-saving and effective pilot.

Angioplasty, Balloon↗

Midterm results with the Sorin Monostrut heart valve prosthesis.

OBJECTIVE: To monitor the hematological and clinical sequelae of a single tilting disc cardiac valve prosthesis. DESIGN: Prospective nonrandomized trial. SETTING: University teaching hospital. PARTICIPANTS: All patients receiving a single mechanical cardiac valve prosthesis were offered the Sorin Monostrut valve if they met the criteria for valve use. Seventy-five per cent of the patients entered were in New York Heart Association (NYHA) functional class III or IV. One hundred and forty-seven patients were subsequently followed at three months and then yearly after valve implantation for seven years. MAIN OUTCOME MEASURES: At one year, preoperative indexes of hemolysis were compared with three-month and one-year postoperative values. Actuarial curves for survival, freedom from cerebrovascular events and explantation were constructed for the seven-year follow-up period. RESULTS: Hemolysis, as measured by lactate dehydrogenase values, commonly occurs preoperatively, remaining significantly elevated three months and one year following valve implantation. Serum haptoglobin was normal preoperatively but was significantly low at one year. Anemia was uncommon and most patients had normal reticulocyte counts at one year. At three years, 81% of patients were in NYHA functional class I. CONCLUSIONS: Midterm results show that this valve is structurally reliable and meets all current requirements for a safe mechanical valve.

Adult↗

The effect of topology on estimates of among-site rate variation.

Among-site rate variation, as quantified by the gamma-distribution shape parameter, a or alpha, and the ratio of transition rate to transversion rate (Ts/Tv) influence phylogenetic inference. We examine the effect of topology on estimates of these two parameters in 12S rRNA sequences from nine species of mice belonging to the genera Onychomys and Peromyscus by generating 100 random topologies and estimating these parameters using parsimony and maximum-likelihood methods for each of the random topologies. The parsimony-based estimate of Ts/Tv from the well-corroborated topology falls within the distribution of estimates based on random topologies, whereas the maximum-likelihood estimate of Ts/Tv based on the well-corroborated topology lies well outside the distribution of estimates derived from random topologies. The Ts/Tv ratio derived via maximum-likelihood estimation is three times the parsimony-based estimate, suggesting that parsimony-based estimates are severe underestimates even when the correct topology is used. Both parsimony- and likelihood-based estimates of the gamma-distribution shape parameter (alpha) are sensitive to topology because the best estimates based on the well-corroborated topology are well outside the distributions of estimates derived from random topologies for both methods. We show that the reason for topology dependence is the presence of long internal branches in the underlying topology.

Animals↗

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine.

OBJECTIVE: To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, amlodipine. METHODS: One hundred sixty-eight adult outpatients with mild to moderate hypertension were randomly allocated in double-blind fashion and equal number to receive 80 mg valsartan or 5 mg amlodipine for 12 weeks. After 8 weeks of therapy, in patients whose blood pressure remained uncontrolled, 5 mg amlodipine was added to the initial therapy. Patients were assessed at 4, 8, and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure at 8 weeks. Secondary variables included change in sitting systolic blood pressure and responder rates. RESULTS: Both valsartan and amlodipine were effective at lowering blood pressure at 4, 8, and 12 weeks. Similar decreases were observed in both groups, with no statistically significant differences between the groups for any variable analyzed. For the primary variable the difference was 0.5 mm Hg in favor of valsartan (p = 0.68; 95% confidence interval, -2.7 to 1.7). Responder rates at 8 weeks were 66.7% for valsartan and 60.2% for amlodipine (p = 0.39). Both treatments were well tolerated. The incidence of drug-related dependent edema was somewhat higher in the amlodipine group, particularly at a dose of 10 mg per day (2.4% for 80 mg valsartan; 3.6% for 5 mg amlodipine; 0% for valsartan plus 5 mg amlodipine; 14.3% for 10 mg amlodipine). CONCLUSIONS: The data show that valsartan is at least as effective as amlodipine in the treatment of mild to moderate hypertension. The results also show valsartan to be well tolerated and suggest that it is not associated with side effects characteristic of this comparator class, dihydropyridine calcium antagonists.

Adult↗

A rapid-flow perfusion chamber for high-resolution microscopy.

Perfusion chambers employing laminar flow have dead volumes and unstirred layers which limit the minimum time required to effect a change in the local chemical environment of the sample. We have fabricated and tested a chamber capable of developing turbulent flow at reasonable flow rates of aqueous solutions. Transition to turbulence occurred at approximately equal to 1 mLs-1. To minimize dead space, a dual-exit cross-flow pattern was employed. The chamber was designed to mount on optical microscope stages for visual sample observation supplemented by a variety of techniques, such as fluorescence, light scattering and electrochemical monitoring. As indicated by fluorescence from a fluorescein-labelled protein film adherent to the chamber wall, local pH changes were produced within 200 ms. Use of the chamber is illustrated by measurements of stopped-flow kinetics in both calcium-triggered cortical granule exocytosis and influenza virus haemagglutinin-mediated cell-cell fusion.

Animals↗

Reading level, learning presentation preference, and desire for information among cancer patients.

BACKGROUND AND METHODS: Cancer patients may face a number of obstacles to learning, including complexity of information, inappropriateness of timing and method of presentation, avoidance as a way of coping, and inability to read. Patients' reading levels, preferred learning methods, and desires for information and the usefulness of two instruments in a clinical setting were investigated. One instrument provided information about sociodemographics, desire for information, and learning preferences; the second instrument, the Rapid Estimate of Adult Literacy in Medicine (REALM), assessed reading ability. RESULTS: The 63 patients studied, most of whom were African American, wanted all available information (90%), desired participation in care decisions (68%), and preferred personal interactive learning (77%). The REALM mean score was 50.8, indicating a seventh-to-eighth-grade reading level. Over half read below their stated educational levels and would be unable to read most available patient education materials. CONCLUSIONS: Educational level did not indicate reading ability; the patients could state their desires for information and their learning preferences, and the REALM was easy to use.

Adult↗

Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation.

In a molecular, microbiologic, and case-control study to describe the epidemiology of ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection, 32 unique isolates were recovered over 31 months from the blood of patients hospitalized in a 900-bed hospital in Chicago. Multivariate analysis revealed cases occurred more frequently in debilitated nursing home patients with central venous catheters than in younger, healthier patients. Mortality rates were similar for cases and controls. Case-patients were less likely to die if they received appropriate antibiotic treatment within 3 days of bacteremia onset (P = .02). Pulsed-field gel electrophoresis analysis indicated a polyclonal outbreak, with strain-specific temporal and geographic clustering. Isoelectric focusing results suggested that a predominant enzyme, TEM-10, was responsible for the ceftazidime resistance. The resistance gene was usually carried on a large conjugative plasmid. The polyclonality of the resistant strains suggests that ceftazidime resistance due to TEM-10 is now endemic in Chicago.

Adolescent↗

Conserved sequence motifs, alignment, and secondary structure for the third domain of animal 12S rRNA.

Secondary structure models are an important step for aligning sequences, understanding probabilities of nucleotide substitutions, and evaluating the reliability of phylogenetic reconstructions. A set of conserved sequence motifs is derived from comparative sequence analysis of 184 invertebrate and vertebrate taxa (including many taxa from the same genera, families, and orders) with reference to a secondary structure model for domain III of animal mitochondrial small subunit (12S) ribosomal RNA. A template is presented to assist with secondary structure drawing. Our model is similar to previous models but is more specific to mitochondrial DNA, fitting both invertebrate and vertebrate groups, including taxa with markedly different nucleotide compositions. The second half of the domain III sequence can be difficult to align precisely, even when secondary structure information is considered. This is especially true for comparisons of anciently diverged taxa, but well-conserved motifs assist in determining biologically meaningful alignments. Patterns of conservation and variability in both paired and unpaired regions make differential phylogenetic weighting in terms of "stems" and "loops" unsatisfactory. We emphasize looking carefully at the sequence data before and during analyses, and advocate the use of conserved motifs and other secondary structure information for assessing sequencing fidelity.

Animals↗

Large differences in substitutional pattern and evolutionary rate of 12S ribosomal RNA genes.

We demonstrate using Drosophila, periodical cicadas, and hominid primates, that the molecular clock based on animal mitochondrial small-subunit (12S) rRNA genes ticks at significantly different relative rates depending on which taxa and which region of the gene are examined. Drosophila, which are commonly used as model taxa, are evolving in a highly peculiar manner with the majority of sites in the 3' half of the 12S gene apparently invariant. The analogous 3' half of the mitochondrial large-subunit rRNA gene (16S) appears to be similarly constrained. It is surprising that these regions that are already highly constrained in all animals should be even more constrained in Drosophila, especially when the Drosophila mitochondrial genome as a whole does not display a similar rate slowdown. This extreme 12S rate slowdown is not apparent in periodical cicadas or hominid primates and appears to be related to strong structural and functional constraints rather than a depressed mutation rate. Finally, the slow average rate of evolution in the third domain of Drosophila does not imply that the few variable sites lack multiple hits.

Animals↗

Expiratory muscle endurance performance after exhaustive submaximal exercise.

The aim of our study was to describe the endurance capacity of the expiratory muscles and to determine whether it is altered after exhaustive cycling exercise. Subjects performed repeated maximal expiratory efforts against a closed breathing valve, with and without prior exercise performed at a work rate that elicited 75% of the maximum ventilation rate. Each expiratory effort lasted 6 s, was separated by 10 s of rest, and was initiated from the end-expiratory lung volume. Endurance performance was assessed by measuring the decline in area under the pressure*time curve over 39 contractions. Prior exhaustive exercise attenuated the ability to generate and sustain maximal expiratory pressure (P = 0.013) and resulted in significant declines in the integrated electromyogram of the rectus abdominis (P = 0.005) and external oblique (P = 0.036) abdominal muscles. Each subject also performed a handgrip endurance task before and after exhaustive exercise on a separate day. Prior exercise had no effect on handgrip endurance performance, suggesting that the decline in expiratory muscle performance after exercise was not the result of reduced motivation. We conclude that the ability to maximally activate the abdominal expiratory muscles and to generate maximum expiratory pressure is impaired after exhaustive exercise. Declines in the surface integrated electromyogram despite maximal effort is consistent with findings in limb muscles and is thought to be due to a slowing of motoneuron firing rates or to neuromuscular transmission failure.

Adult↗

Control of nasal dilator muscle activities during exercise: role of nasopharyngeal afferents.

Our primary aim was to determine whether reducing the activity of nasal airway receptors would influence drive to the nasal dilator muscles (NDMs) during exercise. We used lidocaine (2%) or nasal splints to diminish afferent airway receptor activity and measured the electromyogram (EMG) activity of the NDMs during incremental bicycle exercise in subjects who breathed nasally. NDM EMG activities increased as a function of exercise intensity but were not changed by lidocaine and were only slightly reduced by splinting. Similarly, neither intervention altered the normal decrease in NDM EMG activity associated with reductions in airway resistance evoked by He-O2 breathing. We also compared the NDM EMG response to exercise with that evoked by CO2 rebreathing at rest to determine whether the nature of the ventilatory stimulus influences drive to the NDMs; comparisons were made at constant levels of nasal inspired ventilation and, therefore, constant total ventilatory output. The increase in EMG activity was much higher during exercise compared with hyperoxic hypercapnia. In conclusion, 1) desensitizing the nasal airway does not alter NDM activity significantly during exercise and 2) exercise results in much greater increases in NDM activity compared with hypercapnia, indicating that different ventilatory stimuli can evoke more or less activation of upper airway motoneurons, even when comparisons are made at constant levels of total ventilatory output.

Adult↗

Biological and immunological characterization of inhibin forms in human plasma.

A number of immunoassay methods have been developed recently to detect specifically the bioactive alpha-beta A subunit inhibin dimer (inhibin A) in human plasma. However, the specificity of these assays in terms of their ability to detect the range of inhibin forms found in plasma and their relationship to bioactivity have not been investigated. Inhibin was fractionated from human follicular fluid (hFF) and serum/plasma from women stimulated with gonadotropins (IVF serum), and from postmenopausal and male plasma, using a combined immunoaffinity/preparative SDS-PAGE procedure. The molecular weight profile of inhibin was established by inhibin in vitro bioassay, three alpha-beta A subunit specific immunoassays, and three alpha subunit-directed immunoassays that detect the alpha subunit as well as inhibin A and B forms. In hFF inhibin forms of 33, 36, 55 and 66K were detected by in vitro bioassay and by most immunoassays except for 33 k inhibin, which was nondetectable by one alpha-beta A ELISA. The alpha subunit-directed assays also detected activity in the 29-31K region, in some assays in considerably high levels. In IVF serum in vitro bioactivity and immunoactivities were detected between 27 and 100K with the alpha-beta A assays failing to detect all bioactive forms. Alpha subunit-directed assays gave similar immunoactive profiles. Neither in vitro bioassay nor alpha-beta A assays detected activity in post-menopausal plasma or male plasma, while alpha subunit-directed assays showed peaks predominantly at 36 k, although at low levels. It is concluded that dimeric inhibin A specific assays detected bioactive inhibin forms in hFF and to a lesser extent in IVF serum. Alpha subunit-directed assays correlated poorly with in vitro bioassay in hFF because of the high alpha subunit levels in this sample. The higher correlation between these assays in IVF serum suggested that there was little free alpha subunit. The 36K form in male plasma may be free alpha subunit or inhibin B.

Animals↗

Characterization and determination of the biological activities of noncleavable high molecular weight forms of inhibin A and activin A.

Recombinant expression of human alpha- and beta A-inhibin subunit cDNAs in mammalian 293 cells results in the secretion of 20-53K free alpha-subunit-derived products, 30-105K alpha beta A-inhibin dimers, and 24-110K beta A-activin dimers. The present study verifies that the wide variation in the size of these products is due to incomplete cleavage of the proteolytic processing sites and the differential glycosylation of the N-linked glycosylation site at amino acid number 302 in the alpha C-subunit. The identity of each of these products was established by mutagenesis of proteolytic processing sites and N-linked glycosylation sites, combined with the analysis of transfection products by immunoprecipitation and one- and two-dimensional SDS-PAGE (SDS/SDS-beta-ME). Transient expression of processing site mutants of the alpha- and beta A-subunits in 293 cells was used to generate microgram quantities of noncleavable 55K and 65K inhibin dimers, and noncleavable 110K activin A dimers. The 55K and 65K inhibin A forms were purified and found to be fully biologically active in a rat pituitary cell bioassay. The 110K high molecular weight (HMW) form of human activin A failed to show any FSH-releasing activity in the pituitary assay. Since radioactively labeled 55K and 65K inhibin A and 110K activin A remained intact after incubation with rat pituitary cells for 72 h, there appears to be no conversion of these dimers to lower molecular weight forms by proteolytic cleavage at additional sites. These results show for the first time that 55K and 65K inhibit A are intrinsically biologically active and do not require cleavage to the 32K form for activation. In contrast, cleavage of the 110K activin A precursor to the 24K form would appear to be necessary for activity.

Activins↗