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PubMed2006

Efficacy of a milbemycin oxime-praziquantel combination product against adult and immature stages of Toxocara cati in cats and kittens after induced infection.

Two studies were performed to examine the efficacy of milbemycin oxime against fourth-stage larvae or adults of Toxocara cati. In the study to determine efficacy against fourth-stage larvae, 20 domestic shorthair cats were inoculated with 500 embryonated eggs. Four weeks after inoculation, the animals were allocated to two groups, and cats in one group were treated with medicated tablets containing 4 mg milbemycin oxime and 10mg praziquantel (MILBEMAX) and cats in the other group with placebo tablets. Seven days after treatment the animals were euthanatized and necropsied for worm counting. The number of worms found was significantly (p=0.0002) lower in cats treated with medicated tablets than in cats treated with placebo tablets. The reduction in the number of worms was 96.53%. In the study to determine efficacy against mature adult worms, 13 kittens were inoculated with T. cati embryonated eggs. On day 45 after inoculation and after the infection had been confirmed through faecal examinations for 11 out of the 13 animals, the 11 infected animals were allocated to two groups and treated as in the first study. Seven days after treatment, all animals were euthanatized and necropsied for worm counting. The number of worms found was significantly (p=0.0043) lower in kittens treated with medicated tablets than in kittens treated with placebo tablets. The reduction in the number of worms was 95.90%. No adverse effects were recorded during either study. It is concluded that the milbemycin oxime-praziquantel tablets that were used are efficacious for the control of T. cati infections in cats.

Aging↗
PubMed2004

The Netrin receptor Neogenin is required for neural tube formation and somitogenesis in zebrafish.

The Netrin receptor Deleted in colon cancer (Dcc) has been shown to play a pivotal role in the guidance of nascent axons towards the ventral midline in the developing nervous systems of both vertebrates and invertebrates. In contrast, the function during embryogenesis of a second Dcc-like Netrin receptor Neogenin has not yet been defined. We used antisense morpholino oligonucleotides to knockdown Neogenin activity in zebrafish embryos and demonstrate that Neogenin plays an important role in neural tube formation and somitogenesis. In Neogenin knockdown embryos, cavitation within the neural rod failed to occur, producing a neural tube lacking a lumen. Somite formation was also defective, implicating Neogenin in the migration events underlying convergent extension during gastrulation. These observations suggest a role for Neogenin in determining cell polarity or migrational directionality of both neuroectodermal and mesodermal cells during early embryonic development.

Animals↗
PubMed2006

Neotomine-peromyscine rodent systematics based on combined analyses of nuclear and mitochondrial DNA sequences.

Recently, sequences from two nuclear genes (exon 6 of the dentin matrix protein 1 gene and intron 7 of the beta-fibrinogen gene) and one mitochondrial gene (cytochrome b gene) were used independently in an attempt to resolve phylogenetic relationships within the neotomine-peromyscine complex. Although these studies provided testable hypotheses regarding this group of rodents, the affinities of certain tribes and genera remain uncertain. To elucidate these relationships, the three data partitions were tested for heterogeneity and then concatenated according to conditional data combination and total evidence approaches. Support was found for five clades, four of which correspond to well recognized tribes (the Neotomini, Peromyscini=Reithrodontomyini, Baiomyini, and Tylomyini). Recommendations are made regarding the recognition of Ochrotomys as a tribe of its own, the Ochrotomyini, paralleling other recent findings. The Peromyscini, Baiomyini, and Ochrotomyini are unresolved in relation to each other, but as a whole are sister to the Neotomini. The Tylomyini is basal to all clades. It appears that combined data from the nuclear and mitochondrial genes (analyzing all three partitions simultaneously) resulted in the best phylogenetic hypothesis regarding the complex.

Animals↗
PubMed1995

Exercise intensity does not effect body composition change in untrained, moderately overfat women.

OBJECTIVE: To determine whether exercise intensity effects a change in body composition. DESIGN/SUBJECTS: Twelve untrained, moderately overfat, weight-stable women were randomly assigned to a high-intensity (80% VO2max) or low-intensity (50% VO2max) exercise group. Subjects trained four times per week for 12 weeks in monitored sessions, with a duration sufficient to expend 300 kcal. During this time, subjects were instructed to maintain their normal diet and activity patterns. OUTCOME MEASURES: Pretesting and posttesting included measurement of height, weight, body fat (via hydrostatic weighing), seven skinfold sites, seven circumference sites, and VO2max. STATISTICAL ANALYSES: Results were analyzed using the Student's t test and paired samples t test. RESULTS: Posttesting revealed no significant between-group differences for change in weight, percent body fat, fat mass, fat-free mass, sum of skinfold measurements, or sum of circumference measurements. Mean weight loss was 0.7 lb for the high-intensity group (P = .55) and 3.3 lb for the low-intensity group (P = .03). Hydrostatic data revealed that each group lost an identical amount of fat (5.0 lb), but the high-intensity group gained more than twice as much fat-free mass (4.3 vs 1.8 lb). The greater increase in fat-free mass by the high-intensity group explains why the low-intensity group had a greater absolute weight loss. APPLICATIONS/CONCLUSIONS: This study suggests that fat loss is a function of energy expended rather than exercise intensity. Therefore, if fat loss is the goal and time is limited, persons should exercise safely at as high an intensity as tolerable to expend as much energy as possible during their allotted time.

Adult↗
PubMed1996

Role of spectral measures of heart rate variability as markers of disease progression in patients with chronic congestive heart failure not treated with angiotensin-converting enzyme inhibitors.

Measures of heart rate variability in the frequency domain quantify autonomic activity. However, the relation of these measures to the severity of ventricular dysfunction in patients with congestive heart failure remains uncertain. We applied spectral analysis of heart rate variability to 24-hour Holter monitor recordings obtained from 20 patients with congestive heart failure who were not treated with angiotensin-converting enzyme inhibitors to determine whether significant changes in parameters of heart rate variability reflect the progression of symptoms in patients with ventricular failure. Both total and low-frequency heart rate spectral power were seen to decrease with worsening New Heart Associate (NYHA) functional class. A significant (p = 0.04) higher total power was noted in NYHA class II than in class III patients (3.0 x 10(-3) +/- 3.6 10(-4) and 2.5 x 10(-3) +/- 5.9 x 19(-4) [beats/min]2, respectively). Similarly, low-frequency heart rate spectral power was significantly (p = 0.008) higher in class II than in class III patients (1.7 x 10(-3) +/- 4.6 x 10(-4) and 1.1 x 10(-3) +/- 3.5 x 10(-4) [beats/min]2, respectively). Only the low-frequency component of the spectrum was directly correlated with left ventricular ejection fraction (LVEF) (r = 0.40) with a trend toward statistical significance (p = 0.07). Measures of heart rate variability and the changes in autonomic tone that they reflect may therefore serve as markers of the extent of disease progression in patients with congestive heart failure.

Adult↗
PubMed1996

Vascular hypertrophy is an early finding in essential hypertension and is related to arterial pressure waveform contour.

The effects of hypertension on the arterial vasculature were examined in a study group of 20 patients with newly diagnosed essential hypertension, 18 patients with chronic essential hypertension, and 32 control subjects with normal blood pressure. Left ventricular mass was determined echocardiographically. Carotid artery intimal-medial thickness was measured by means of B-mode ultrasound imaging, and carotid arterial waveforms were obtained by applanation tonometry. Compared with that in control subjects, carotid intimal-medial thickness was increased in patients with chronic hypertension (0.74 +/- 0.17 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.01) and in patients with newly diagnosed hypertension (0.66 +/- 0.12 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.05). Left ventricular mass was also higher in patients with chronic hypertension than in control subjects but was very similar between control subjects and those with newly diagnosed hypertension. Both the group with early hypertension and the group with chronic hypertension had an increased incidence of early waveform reflection evident on carotid arterial waveform examination. By multiple regression analysis, independent predictors of increased carotid intimal-medial thickness were age, systolic arterial pressure, and Murgo class of arterial waveform. Conduit arterial wall thickening precedes left ventricular remodeling in essential hypertension and is significantly related to the degree of pressure elevation and the arterial waveform contour.

Age Factors↗
PubMed1999

A randomized trial of ecadotril versus placebo in patients with mild to moderate heart failure: the U.S. ecadotril pilot safety study.

OBJECTIVE: To determine the short-term safety and tolerability of the addition of ecadotril to conventional therapy in patients with mild to moderate heart failure. METHODS: Fifty ambulatory patients, 18 to 75 years of age, with mild to moderate heart failure, left ventricular ejection fraction </=35%, taking stable doses of angiotensin-converting enzyme inhibitor, diuretics, and optionally digoxin were enrolled in a randomized, double-blind, placebo-controlled dose-escalation study of ecadotril 50 to 400 mg twice daily versus conventional therapy alone. RESULTS: No increases in deaths, serious adverse events, or dropouts from adverse events were observed for the ecadotril group compared with placebo. The serum measures of neurohormonal activation were highly variable. Changes in signs and symptoms of heart failure, New York Heart Association class, and patient self-assessment of symptoms were not observed with ecadotril therapy; however, the study was not designed to detect differences in these parameters. CONCLUSION: In this small pilot study, ecadotril in doses of 50 to 400 mg twice daily was generally well-tolerated and without severe short-term adverse effects in patients with mild to moderate heart failure. Evaluation of the clinical efficacy and long-term safety of ecadotril and other neutral endopeptidase inhibitors in patients with heart failure requires further study.

Adolescent↗
PubMed2003

Impact of serial changes in cardiac hemodynamics on exercise performance in patients with heart failure due to ischemic and nonischemic cardiomyopathy.

Although prior studies have examined the role of central and peripheral hemodynamics on exercise tolerance within populations of patients with heart failure, a clear relation between hemodynamics and exercise has not been demonstrated. This may be due to the inability to control for other factors that may influence exercise performance. To isolate the impact of hemodynamics on exercise, we studied the relation between changes in these factors within individual patients studied on 2 occasions. A consecutive series of 133 ambulatory patients with heart failure were evaluated on 2 separate occasions with right-sided cardiac catheterization and treadmill cardiopulmonary exercise testing. Linear regression models were constructed and correlation coefficients were determined to examine the relation between changes in hemodynamic variables and changes in exercise variables over time for each patient. A significant correlation between peak oxygen consumption (VO(2)) and pulmonary arterial wedge pressure was found for both the first (r = -0.316, p <0.001) and second (r = -0.183, p = 0.029) tests. A stronger inverse correlation between the change in pulmonary arterial wedge pressure and change in peak VO(2) was observed in the study patients (r = -0.470, p <0.001). Similar correlations were found between change in peak VO(2) and changes in pulmonary arterial pressures. Changes in left ventricular filling pressure influence exercise tolerance in patients with heart failure due to left ventricular systolic dysfunction. Interpretation of cardiopulmonary exercise testing for the purpose of determining cardiac transplantation eligibility will be improved with knowledge of left ventricular filling pressure.

Adolescent↗
PubMed1983

Ventricular electrical instability: a predictor of death after myocardial infarction.

The results of a prospective study of ventricular electrical instability after myocardial infarction (MI) are presented. Ventricular electrical stability was assessed using a standardized protocol of programmed stimulation in 165 hemodynamically stable patients 6 to 28 days after acute MI. Ventricular electrical instability was defined as induction at programmed stimulation of ventricular fibrillation (VF) or ventricular tachycardia (VT) lasting at least 10 seconds. Of 165 MI survivors, 38 (23%) had ventricular electrical instability. No significant differences were noted between stable and unstable patients in terms of coronary prognostic index, elevation of serum creatine phosphokinase, coronary anatomy, site of MI, or frequency of VT within 48 hours of MI. The mean follow-up period was 8 months (range 0 to 12). There were 7 deaths in stable patients (5 from cardiogenic shock, 1 from septicemia, and 1 unwitnessed) and 10 deaths in unstable patients (8 instantaneous, 1 from cardiogenic shock, and 1 unwitnessed) during the subsequent year. In addition, 2 of 127 stable patients and 4 of 38 unstable patients had spontaneous VT from which they were satisfactorily resuscitated. Thus, the sensitivity of ventricular electrical instability as a predictor of instantaneous death or spontaneous VT was 86% and the specificity 83%. The predictive accuracy of the absence of ventricular electrical instability as an indicator for the absence of instantaneous death or spontaneous VT was 98%. The predictive accuracy of the presence of ventricular electrical instability as a predictor of instantaneous death or spontaneous VT was 32%. Thus, patients with ventricular electrical instability after MI have a high risk of instantaneous death within 1 year; patients without ventricular electrical instability after MI have a low risk of instantaneous death within 1 year; prospective studies of antiarrhythmic therapy and measures to prevent reinfarction and optimize left ventricular performance are required to determine whether instantaneous death can be prevented in unstable patients; and therapy to prevent reinfarction and optimize left ventricular performance may offer the best chance to improve prognosis in stable patients.

Adrenergic beta-Antagonists↗
PubMed1996

Assessment of left ventricular function by meridional and circumferential end-systolic stress/minor-axis shortening relations in dilated cardiomyopathy.

Echocardiographic meridional wall stress-endocardial shortening relations provide estimates of left ventricular (LV) contractility that do not uniformly detect myocardial dysfunction despite severe symptoms in dilated cardiomyopathy. To improve detection of myocardial dysfunction in patients with congestive heart failure (CHF) due to dilated cardiomyopathy, echocardiographic meridional and circumferential end-systolic stress were related to endocardial and midwall shortening in 42 patients (95% dead within a mean of 22 months) with dilated cardiomyopathy and 140 normal subjects. A method to estimate LV long-axis dimension from M-mode minor-axis epicardial measurements was developed in a separate series of 115 subjects. Endocardial shortening to meridional wall stress relation identified 31 of 42 CHF patients falling below the 95% normal confidence interval of the reference population; use of midwall shortening decreased this number to 26 (p = NS). The use of circumferential wall stress identified 39 of 42 patients with subnormal endocardial LV shortening and 41 of 42 patients with depressed midwall performance (p < 0.01 vs use of meridional stress). The circumferential/meridional wall stress ratio was 2.6 +/- 0.5 in normal subjects and 1.3 +/- 0.2 in CHF patients (p < 0.0001). Thus, use of circumferential end-systolic stress as the measure of afterload improves the detection of myocardial dysfunction by stress/shortening relations in patients with CHF. The ratio between the 2 stresses decreases with more spherical LV shape. Midwall and endocardial shortening measurements are equivalent in the setting of thin LV walls as occurs in dilated cardiomyopathy.

Adult↗
PubMed1997

The integrated effects of angiotensin II.

In recent years, a prodigious amount of information has been gathered regarding the relationship between vascular biology and the mechanisms underlying cardiovascular disease. Activation of elements of the reninangiotensin system (RAS) appear to play an important role in the development and progression of conditions such as hypertension, coronary artery disease, and heart failure. Indeed, converging lines of evidence indicate that angiotensin-converting enzyme (ACE) regulates a delicate balance among a multitude of factors responsible for vascular tone, cellular growth promotion and inhibition, and pro- and anti-inflammatory effects. Because angiotensin II inhibits fibronectin, stimulates expression of plasminogen activator inhibitors, and degrades bradykinin, thereby impairing production of nitric oxide, ACE and the RAS are also involved in thrombosis and fibrinolysis. The favorable effects of ACE inhibition on endothelial function and, potentially, on cardiovascular morbidity and mortality are believed to result not only from angiotensin II suppression but also its consequent bradykinin preservation and nitric oxide production.

Angiotensin II↗
PubMed1997

Stevens-Johnson syndrome associated with carvedilol therapy.

Stevens-Johnson syndrome, related to carvedilol use, has not been previously reported as a serious adverse experience requiring hospitalization. We report this reaction in a 71-year-old man with stable ischemic cardiomyopathy.

Adrenergic beta-Antagonists↗
PubMed1997

Significance of prolonged left ventricular wall motion abnormalities after exercise echocardiography following non-Q-wave acute myocardial infarction.

Exercise echocardiography was used to assess myocardial ischemia after non-Q-wave acute myocardial infarction in 40 consecutive patients. Resting parasternal long- and short-axis views and apical 4- and 2-chamber views were recorded, digitized, and stored. A maximal symptom-limited exercise test was performed within 21 days (mean 17.7 +/- 3) using a cycle ergometer with continuous monitoring and the echocardiogram was repeated in the same views. Resting and exercise echocardiograms were then compared. Coronary angiography was performed in all patients within 21 days of exercise echocardiography. Stenosis in > or =50% of the lumen diameter was considered significant. Of the 40 patients studied, 29 (72%) had continuing angina and 11 (28%) had no angina. Eighteen patients (62%) with angina developed angina during exercise testing and 19 (65%) developed ST-segment depression. In patients without angina, 1 (9%) developed postexercise angina and 2 (18%) developed ST-segment depression. The mean wall motion score index after exercise increased from 1.2 +/- 0.3 to 1.8 +/- 0.4 in patients with continuing angina (p <0.001) and from 1.2 +/- 0.3 to 1.4 +/- 0.3 in patients without angina (p = NS). Prolonged wall motion abnormalities lasting >20 minutes persisted in > or =1 segment in 27 of 29 patients (93%) with angina or in 2 of 1 1 patients (18%) without angina (p <0.001). Patients with continued angina had predominantly 3-vessel coronary artery disease (22 of 29 [76%]) or 2-vessel disease (7 of 29 [24%]), and those without angina had 1-vessel disease (6 of 11 [55%]) or 2-vessel disease (4 of 11 [36%]). One patient had 3-vessel disease. The duration of wall motion abnormality demonstrated a significant relation to 2- and 3-vessel coronary artery disease (p <0.001). Thus, patients with non-Q-wave acute myocardial infarction had a high incidence of multivessel coronary disease not necessarily detected on routine exercise testing. There was also a significant incidence of prolonged wall motion abnormality.

Case-Control Studies↗
PubMed1997

The sympathetic nervous system and the renin-angiotensin-aldosterone system in cardiovascular disease.

Both the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) have central roles in vascular adaptive processes. Stimulation of the 2 systems has been demonstrated in a range of cardiovascular disorders, including congestive heart failure and hypertension. However, elucidation regarding the interactions of the many factors involved in these 2 systems is lacking. Angiotensin-converting enzyme inhibitors have been used to reveal the contribution of some elements in the RAAS. Until relatively recently, little was known about the specific disturbances of the sympathetic nervous system in cardiovascular disease. Plasma norepinephrine levels, an indicator of sympathetic activity, have limited value because they are affected by various physiologic processes in addition to sympathetic activation. Newer approaches to the assessment of neurohormonal activity include the determination of the power content of heart-rate variability. More specific probes may lead to a better comprehension of neurohormonal physiology in health and disease and underlie future therapeutic advances targeted to prevention and treatment of specific syndromes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

An intensive communication intervention for the critically ill.

PURPOSE: We sought to determine the effects of a communication process that was designed to encourage the use of advanced supportive technology when it is of benefit, but to limit its burdens when it is ineffective. We compared usual care with a proactive, multidisciplinary method of communicating that prospectively identified for patients and families the criteria that would determine whether a care plan was effective at meeting the goals of the patient. This process allowed caregivers to be informed of patient preferences about continued advanced supportive technology when its continuation would result in a compromised functional outcome or death. MATERIALS AND METHODS: We performed a before-and-after study in 530 adult medical patients who were consecutively admitted to a university tertiary care hospital for intensive care. Multidisciplinary meetings were held within 72 hours of critical care admission. Patients, families, and the critical care team discussed the care plan and the patients' goals and expectations for the outcome of critical care. Clinical "milestones" indicative of recovery were identified with time frames for their occurrence. Follow-up meetings were held to discuss palliative care options when continued advanced supportive technology was not achieving the patient's goals. We measured length of stay, mortality, and provider team and family consensus in 134 patients before the intensive communication intervention and in 396 patients after the intervention. RESULTS: Intensive communication significantly reduced the median length of stay from 4 days (interquartile range, 2 to 11 days) to 3 days (2 to 6 days, P = 0.01 by survival analysis). This reduction remained significant after adjustment for acute physiology and chronic health evaluation (APACHE) 3 score [risk ratio (RR) = 0.81; 95% confidence interval (CI), 0.66 to 0.99; P = 0.04). Subgroup analysis revealed that this reduction occurred in our target group, patients with acuity scores in the highest quartile who died (RR = 0.60; 95% CI, 0.38 to 0.92; P = 0.02). The intervention, which allowed dying patients earlier access to palliative care, was not associated with increased mortality. CONCLUSIONS: Intensive communication was associated with a reduction in critical care use by patients who died. Our multidisciplinary process targeted advanced supportive technology to patients who survived and allowed the earlier withdrawal of advanced supportive technology when it was ineffective.

APACHE↗