Biomedical subjects

C Benedict

Publications and source records attributed to C Benedict.

At least 19 recordsLinked to original sources

PubMed1998

Factors influencing exercise performance in patients with left ventricular dysfunction. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

BACKGROUND: The determinants of exercise performance are multifactorial and incompletely understood in patients with symptomatic left ventricular (LV) dysfunction, with much less information regarding asymptomatic LV dysfunction. This study assessed the hemodynamics and neurohormonal factors influencing exercise performance in patients with LV ejection fractions > or =0.35, both symptomatic and asymptomatic, enrolled in Studies of LV Dysfunction. METHODS AND RESULTS: We studied 103 patients enrolled prospectively in Studies of LV Dysfunction before randomized therapy; 38 were symptomatic and 65 had no or minimal symptoms. By using rest-exercise gated equilibrium radionuclide ventriculography and cuff blood pressure, we assessed the heart rate, LV and right ventricular (RV) volumes and ejection fractions, total peripheral resistance, the LV peak systolic pressure/end systolic volume ratio as an index of contractility, and plasma renin and norepinephrine at rest and during maximal graded supine bicycle ergometer exercise. Changes between rest and exercise were evaluated as indices of cardiovascular reserve. The cumulative workload ranged from 120 to 2,100 watt-min. At rest, the LV ejection fraction was 0.30 in asymptomatic patients and 0.25 in symptomatic patients, respectively (P < .0004). During exercise, asymptomatic patients had greater increases in heart rate, systolic blood pressure, LV ejection fraction, and cardiac output than symptomatic patients (P > or = .05). Combining all patients, the strongest univariate correlates of exercise workload were the ability to increase heart rate (r = 0.70), the pressure/volume ratio (r = 0.63), and systolic blood pressure (r = 0.55), and to decrease the total peripheral resistance (r = -0.47) with moderate correlations for the ability to increase LV and RV ejection fractions (r = 0.33 and 0.35, respectively) (P < .0008). By multivariate analysis, workload was modeled best by the changes in four factors: heart rate, systolic blood pressure, and the LV and RV ejection fractions (R2 = 0.54, P < .001). CONCLUSION: Exercise performance and its hemodynamics differed in patients with symptomatic and asymptomatic LV dysfunction. Rather than features at rest, the reserve capacities for increasing heart rate, systolic blood pressure, and the LV and RV ejection fractions were the predominant cardiac mechanisms related to greater exercise performance.

Adult↗

PubMed1997

Characteristics of good anaesthesia teachers.

PURPOSE: The Department of Anaesthesia undertook a qualitative study to a) reveal the characteristics of teachers who had been identified as "good," and b) explore the levels of epistemological development (defined as conceptualization of knowledge) that are evidenced. Changes in medical education curricula have focused attention on the ways in which medical teaching staff conceptualize the learning/teaching interactions and their ability to alter or modify their teaching styles. Teachers are often assessed or informally recognized as "good teachers," but there are few indicators to guide what is meant by the label in anaesthesia. METHODS: Teachers who had consistently received overall ratings of 4+ on a 5 point rating scale over a five year period were selected to be interviewed. Data were analyzed a) noting key teaching characteristics and patterns of teaching and b) within the framework of adult development theories. RESULTS: Good teachers in Anaesthesia all identified six characteristics necessary for good teaching. They were characterised by their "inquiry" approach to teaching, their complexity of thought and their functioning at higher relativistic/Commitment levels of epistemological development. CONCLUSION: Teaching in anaesthesia is depicted by the need to address multiple aspects of thinking and action. Good teachers are aware of these aspects and include techniques that offer residents opportunities to develop their thinking skills to deal with medical complexities as well as guiding learners to increase their knowledge. The interviewed teachers' revealed approaches to teaching and learning that indicated their own personal cognitive complexity and levels of development.

Adult↗

PubMed1997

Immunization with a plasmid expressing pneumococcal surface protein A (PspA) can elicit protection against fatal infection with Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) is a protectioneliciting protein of Streptococcus pneumoniae. We observed that immunization of BALB/c mice with a plasmid expressing PspA significantly protected the mice from lethal challenge with S. pneumoniae when compared to control mice that received injections of the plasmid vector alone. The plasmid construct expressing PspA has been designated pKSD2601. Mice immunized intramuscularly with pKSD2601 had a mean log of colony-forming units of 2.67 +/- 0.25 pneumococci circulating in their blood at 24 h after challenge as compared with control mice that had a mean log of colony-forming units of 4.95 +/- 0.59. Those mice with lower numbers of pneumococci subsequently survived the challenge. Given the quantitative nature and ultimate end point (ie live versus dead) our mouse model should be useful in working out optimum expression of bacterial genes for DNA immunization.

Animals↗

PubMed1997

B cell development in mice.

The development and establishment of the B Cell Repertoire is the net result of both genetic and environmental forces. The primary event at the genetic level is Ig gene rearrangement resulting in numerous possible combination of genes which can be further modified by somatic events such as N segment addition and somatic mutation. Environmental forces in the form of self and exogenous Ags also shape the repertoire by positively or negatively selecting B cells according to the specificity of their Ig receptors. These are dynamic processes beginning with the earliest expression of immunoglobulins in fetal life and continuing throughout life. In this review we discuss the genetic and selective mechanisms responsible for differences in the early immune system compared to that of the adult.

Animals↗

PubMed1996

Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD).

OBJECTIVES: This study sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization. BACKGROUND: Elevated levels of tumor necrosis factor-alpha have been identified in 30% to 40% of patients with heart failure. However, it is unclear which subsets of patients with heart failure elaborate tumor necrosis factor-alpha. It is also unclear what the mechanism for the increased expression of proinflammatory cytokines is. METHODS: Tumor necrosis factor-alpha and interleukin-6 levels were analyzed by enzymes-linked immunoassay using randomly selected plasma samples from patients in functional classes I to III who were enrolled in neurohormonal substudies of the SOLVD trial; age-matched healthy subjects served as the control group. RESULTS: Plasma levels of tumor necrosis factor-alpha (p < 0.001) were elevated in patients in functional classes I to III ([mean +/- SD] 1.95 +/- 0.54, 2.63 +/- 0.48, 6.4 +/- 1.9 pg/ml, respectively) compared with age-matched control subjects (0.75 +/- 0.05 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Plasma levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 +/- 0.55, 6.2 +/- 1.1, 5.22 +/- 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 +/- 0.5 pg/ml and were progressively elevated in relation to decreasing functional status of the patient. Cox proportional-hazards analysis showed that there was a trend toward significance between plasma tumor necrosis factor-alpha (p < 0.07) and survival, whereas there was no significant relation for plasma interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakly (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alpha levels, there was no significance correlation between neurohormonal and proinflammatory cytokine levels. CONCLUSIONS: Circulating levels of proinflammatory cytokines increase in patients as their functional heart failure classification deteriorates. Moreover, activation of the neurohumoral axis is unlikely to completely explain the elaboration of proinflammatory cytokines in heart failure.

Aged↗

PubMed1996

Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group.

PURPOSE: To assess the comparative antiemetic efficacy of single-dose intravenous (IV) dolasetron mesylate and ondansetron in preventing cisplatin-induced nausea and vomiting. PATIENTS AND METHODS: Cancer patients (n = 609) receiving first-course cisplatin chemotherapy were randomized to one of three treatments: 1.8 or 2.4 mg/kg dolasetron mesylate salt (equivalent to 1.3 and 1.8 mg/kg dolasetron base, respectively) or 32 mg ondansetron. Each treatment was infused over 15 minutes, 30 minutes before cisplatin administration. Patients were stratified to cisplatin doses of > or = 70 and less than 91 mg/m2 (n = 368) or > or = 91 mg/m2 (n = 241), administered over < or = 3 hours. Protocol-defined efficacy criteria included complete response (zero emetic episodes and no rescue medication), major response (1 to 2 emetic episodes and no rescue medication), and patients' report of nausea severity and satisfaction recorded on a 100-mm visual analog scale (VAS). RESULTS: The three treatments met protocol-specified criteria for equivalence. Complete response rates for dolasetron mesylate 1.8 mg/kg, 2.4 mg/kg, and ondansetron, respectively, were 49.2%, 45.6%, and 50.4% for patients in the lower cisplatin stratum (mean, 74.7 mg/m2) and 36.8%, 31.3%, and 31.8% in the higher cisplatin stratum (mean, 100.6 mg/m2). No significant differences were observed in the extent of nausea with either dolasetron dose compared with ondansetron. Less nausea was noted with 1.8 mg/kg dolasetron compared with the 2.4 mg/kg dose (P = .044) All three antiemetic treatments were well tolerated. Asymptomatic electrocardiogram changes were recorded with both dolasetron and ondansetron. CONCLUSION: A single IV dose of dolasetron mesylate (1.8 or 2.4 mg/kg) has comparable safety and efficacy to a single 32-mg IV dose of ondansetron in patients receiving cisplatin chemotherapy.

Adult↗

PubMed1995

Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy.

BACKGROUND: Studies of Left Ventricular Dysfunction (SOLVD) demonstrated that enalapril therapy significantly improved the clinical course of patients with left ventricular (LV) dysfunction. The goals of this substudy were to evaluate changes in LV structure and function in SOLVD patients and to test the hypothesis that enalapril inhibits remodeling in patients with LV dysfunction. METHODS AND RESULTS: Patients entering both the prevention and treatment arms of SOLVD from 5 of the 23 clinical centers were recruited for this substudy. The 301 patients who participated underwent Doppler-echocardiographic evaluation according to standard protocol before randomization to either enalapril or placebo and again after 4 and 12 months of therapy. Recorded data were analyzed in a blinded fashion at a central core laboratory. Analysis of baseline clinical characteristics showed that patients enrolled in the substudy were generally representative of the SOLVD population, although prevention arm patients were slightly overrepresented in the substudy group (69.8% compared with 61.9% of remaining SOLVD patients). The enalapril group demonstrated significant reductions in the mitral annular E-wave-to-A-wave velocity ratio (due predominantly to a reduction in E-wave velocity), and this response was different from that seen in the placebo group (P = .030). Changes in the E-to-A ratio in the enalapril group correlated significantly with changes in plasma atrial natriuretic peptide (r = .56; P < or = .01). LV end-diastolic and end-systolic volumes increased in placebo but not enalapril-treated patients, and the differences in response between the treatment groups were significant (P = .025 and .019, respectively). LV mass tended to increase in placebo patients and to be reduced in enalapril-treated patients, and the difference in response between the groups was highly significant (P < or = .001). CONCLUSIONS: These data demonstrate that enalapril attenuates progressive increases in LV dilatation and hypertrophy in patients with LV dysfunction. The results support the possibility that the favorable effects of enalapril reported in the SOLVD trials were related to inhibition of LV remodeling.

Adult↗

PubMed1995

Calreticulin, an antithrombotic agent which binds to vitamin K-dependent coagulation factors, stimulates endothelial nitric oxide production, and limits thrombosis in canine coronary arteries.

Coagulation Factor IX/IXa has been shown to bind to cellular surfaces, and Factor IXa expresses its procoagulant activity by assembling into the intrinsic Factor X activating complex (Factors IXa/VIIIa/X), which also forms on membrane surfaces. This led us to identify cellular proteins which bind Factor IX/IXa; an approximately 55-kDa polypeptide was purified to homogeneity from bovine lung extracts based on its capacity to bind 125I-Factor IX in a dose-dependent and saturable manner. From protein sequence data of the amino terminus and internal peptides, the approximately 55-kDa polypeptide was identified as calreticulin, a previously identified intracellular calcium-binding protein. Recombinant calreticulin bound vitamin K-dependent coagulation factors, 125I-Factor IX, 125I-Factor X, and 125I-prothrombin (Kd values of approximately 2.7, 3.2, and 8.3 nM, respectively), via interaction with its C-domain, although it did not affect the coagulant properties of these proteins. 125I-Calreticulin also bound to endothelial cells in vitro (Kd approximately 7.4 nM), and mouse infusion studies showed an initial rapid phase of clearance in which calreticulin could be localized on the vascular endothelium. Exposure of endothelial cells to calreticulin led to dose-dependent, immediate, and sustained increase in the production of nitric oxide, as measured using a porphyrinic microsensor. In a canine electrically induced thrombosis model, intracoronary infusion of calreticulin (n = 7) prevented occlusion of the left circumflex coronary artery in a dose-dependent manner compared with vehicle-treated controls (n = 5). These results indicate that calreticulin interacts with the endothelium to stimulate release of nitric oxide and inhibit clot formation.

Animals↗

PubMed1995

Neurohumoral variability in left ventricular dysfunction. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

The immediate and longer term variability of selected vasoactive- and volume-regulating neurohormones were measured in patients entering a substudy of the Studies of Left Ventricular Dysfunction--a randomized clinical trial in patients with left ventricular ejection fraction < or = 35%. The variability of these hormones has not been determined in a large cohort of patients. Immediate (short-term) variability was assessed by systematically comparing levels after 15 and 30 minutes of supine rest at the initial visit, and longer term variability was assessed by comparing 30-minute supine rest values at the initial visit with corresponding values taken at 30 minutes after 16 to 24 days of stable therapy. Initial values obtained at the first visit after 30-minute supine rest for all 209 patients were (mean +/- SEM) 512 +/- 21 pg/ml pg/ml for plasma norepinephrine, 1.9 +/- 0.2 ng/ml/hr for plasma renin activity, 3.0 +/- 0.1 pg/ml for plasma arginine vasopressin, and 129 +/- 5.3 pg/ml for plasma atrial natriuretic peptide. All variables were moderately increased relative to established normal values. There was a small but significant decrease from 15- to 30-minute supine posture in all neurohormones, except arginine vasopressin. In the presence of stable background therapy, no significant differences were found between measurements obtained after 30 minutes supine rest at the initial visit and 16 to 24 days later. Spearman correlation coefficients corresponding to immediate and longer term variability were high (range 0.55 to 0.79) (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Isolation and characterization of the human interleukin-9 receptor gene.

To better understand the regulation of interleukin-9 (IL-9) receptor expression, we have isolated the genomic clone of the human IL-9 receptor based on its sequence homology with a human IL-9 receptor cDNA isolated from the human megakaryocyte cell line UT-7. The entire genomic structure has been determined. The human IL-9 receptor gene consists of 10 exons spread over approximately 13.7 kb of DNA. The nucleotide sequence of the coding region from the genomic DNA is identical to our cDNA clone. Several blocks of transcriptional control sequence have been identified at the 5' noncoding region of the IL-9 receptor gene that may play an important role in the regulation of the IL-9 receptor gene. A fusion gene containing 659 bp of human IL-9 receptor 5' noncoding region linked to the firefly luciferase gene directed expression of luciferase activity in human embryonic kidney 293 cell line, but not in the mouse fibroblast cell line NIH3T3 cells.

Amino Acid Sequence↗

PubMed1994

Peri-operative anticoagulant effects of heparinization for carotid endarterectomy.

The question of whether or not to reverse heparin following carotid endarterectomy is a topic of debate. The potential reduction of the risk of thrombosis at the endarterectomy site with non-reversal has to be measured against a potential increase in the risk of wound haematoma. This study prospectively followed activated clotting time (ACT) of 42 consecutive patients undergoing carotid endarterectomy. A standard heparin dose of 100 units/kg was used, and heparin reversal was employed only if the wound appeared excessively haemorrhagic at the procedure's completion. Heparin was reversed in 11 patients. Following heparin administration, ACT increased to a mean 2.72 +/- 0.09 times baseline (range 1.84-4.07), and fell with time, until at 3 h after heparin administration mean ACT in the non-reversed patients was 1.48 +/- 0.03 times baseline (range 1.1-2.03). There was one postoperative neurological event (2%), a contralateral hemisphere stroke. No patient developed a frank wound haematoma requiring evacuation, although three patients (7% of the total study group, 9% of patients not receiving heparin reversal) developed neck swelling and symptoms of airway compromise, and were intubated. Measurements of ACT suggest that a heparin dose of 100 units/kg achieves an adequate anticoagulant level in the operative and early postoperative phase, when thrombosis is most likely to occur, and is not associated with an increased risk of wound haematoma. If heparin is to be selectively reversed in patients felt to be at high risk of postoperative haematoma, the decision should be based on an objective measurement such as ACT, and not the surgeon's impression of wound haemostasis.

Aged↗

PubMed1994

Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis.

BACKGROUND: Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction. METHODS AND RESULTS: We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility. CONCLUSIONS: Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function.

Aged↗

PubMed1992

Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions.

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Angina, Unstable↗

PubMed1992

Effectiveness of preload reserve as a determinant of clinical status in patients with left ventricular systolic dysfunction. The SOLVD Investigators.

The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMed1990

Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).

Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p less than 0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy.

Arginine Vasopressin↗

PubMed1989

Nicotine regulation among heavy and light smokers in a non-stressful environment.

The purpose of this study was to assess nicotine regulation among "heavy" and "light" smokers. Previous studies supporting the nicotine regulation model of smoking behavior have suggested that smokers compensate for a reduction in the amount of nicotine available in their cigarette by altering smoking frequency, puff volume, or other aspects of smoking topography. However, little is known about a smoker's decision to smoke a specific cigarette, and the concurrent changes in their blood nicotine. Manipulation of nicotine levels in the blood could play a critical role in smoking maintenance, by regulating the extent and quality of the CNS effects of smoking. In this study, 24 heavy and light smokers (cotinine above or below 260 ng/ml) smoked high- (1.0 mg) or low- (0.5 mg) dose nicotine cigarettes while watching non-stressful movies. Blood nicotine was assessed before and after smoking a preload and free operant cigarette. The results showed that blood nicotine levels after smoking the free operant cigarette were significantly more consistent (lower standard error) for the heavy smokers, following a low dose, as opposed to a high-dose preload. Light smokers showed a non-significant trend towards being more consistent when the high-dose nicotine preload was used. This suggests that heavy smokers may have maximized their dose of nicotine whenever available nicotine was in relatively short supply (low dose condition). However, light smokers may have minimized their exposure when available nicotine was relatively more plentiful (high dose condition).

Adult↗

PubMed1988

Preliminary evaluation of the use of mussel adhesive protein in experimental epikeratoplasty.

We have used a preliminary formulation of a bioadhesive in an experimental model of epikeratoplasty in rabbits. The adhesive, termed mussel adhesive protein (MAP), is a repeating decapeptide polymer that is the natural adhesive substance produced by the common blue mussel (Mytilus edulis) and is used here in conjunction with an enzymatic cross-linking agent. This study marked the first in vivo use of this material in adhering ophthalmic tissue planes. We used a simplified epikeratoplasty technique highlighted by freehand dissection of donor lenticules and host keratotomies. Approximately 10 microL of a combination of MAP and the cross-linking agent was applied directly to the host cornea and the donor lenticules were secured into the keratotomies using eight interrupted 10-0 nylon sutures. All of the sutures were removed 72 hours postoperatively. Eleven of the 15 animals retained their epikeratoplasty lenticules throughout the entire postoperative period. Four animals had initially intact lenticules that sloughed within the first postoperative week; this sloughing, we believe, was attributable to difficulties in tucking irregularly thickened lenticule edges into the keratotomy. In control animals that had lenticules secured with sutures alone, suture removal at 72 hours consistently produced immediate lenticule sloughing. Clinical examinations and histopathologic studies disclosed no untoward effects of the adhesive on the donor or host corneal tissue. We believe that this preliminary study indicates a potential adjunctive role for MAP in epikeratoplasty.

Animals↗

PubMed1988

Electrophysiological monitoring during acoustic neuroma and other posterior fossa surgery.

Techniques used to monitor the function of the seventh and eighth cranial nerves during acoustic neuroma and other posterior fossa surgery are reviewed. The auditory brainstem response (ABR), electrocochleogram (ECochG) and direct recording from the auditory nerve (CNAP) were compared. The best technique is the ECochG, although in many cases, the CNAP should be used as a back-up technique. The CNAP is especially useful for the identification of the auditory nerve. Both can provide real-time feedback on the physiological integrity of the auditory nerve. The ABR may be helpful in monitoring brainstem function. For some procedures, optimal monitoring requires the combined recording of all three techniques. Monopolar constant-voltage intracranial stimulation of the facial nerve is helpful for the identification and preservation of the facial nerve. Audio monitoring of spontaneous electromyographic activity provides real-time feedback on the effect of surgical manipulation of the nerve. Monitoring of ephaptic transmission in the facial nerve during microvascular decompression for hemifacial spasm aids in the identification of the offending vessel.

Action Potentials↗