EEC/COLIPA in vitro photoirritancy program: results of the first stage of validation.
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Biomedical subjects
Publications and source records attributed to J Dupuis.
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Successful prostatic surgery requires aggressive perioperative animal patient management, accurate identification of the disease process, and proper surgical techniques. Overcoming the complications associated with urinary incontinence, sepsis, and neoplasia will help reduce animal patient morbidity and mortality.
A 9-year-old sexually intact male Boxer was euthanatized because of progressive, generalized seizures that were refractory to medical treatment. To try to preserve the breeding line, postmortem epididymal semen extraction was attempted. The testes were excised after the dog was euthanatized, and semen was extracted, frozen, and stored in liquid nitrogen. Approximately 3.5 months later, a suitable recipient was identified, and surgical intrauterine insemination was performed. Fifty-seven days after insemination, a viable pup was born.
The first comprehensive sky survey of the extreme ultraviolet (EUV) spectral range performed by the Extreme Ultraviolet Explorer (EUVE) has uncovered a handful of very bright sources at wavelengths longer than the He I 504 angstroms photoionization edge. Among these objects are four white dwarfs with exceptionally low interstellar medium (ISM) column densities along the line of sight. Analysis of EUV photometry of the He-rich DO white dwarf MCT 0501-2858 and the H-rich DA white dwarf MCT 0455-2812 along one line of sight and of the DA white dwarfs HZ 43 and GD 153 near the north Galactic pole indicates that the overall minimum column density of the neutral material centered on the Sun is N(H I)= 0.5-1.0 x 10(18) cm-2. In the case of MCT 0501-2858, EUV photometric measurements provide a clear constraint to the effective temperature (60,000-70,000 K). Given these neutral hydrogen columns, the actual contribution to the density of neutral species from the immediate solar environment (the "local fluff") would only cover a distance of approximately 2-3 pc (assuming an average density n(H I) = 0.1 cm-3) leaving these lines of sight almost entirely within the hot phase of the ISM. A preliminary examination of the complete EUVE long-wavelength survey indicates that these lines of sight are exceptional and set a minimum column density in the solar environment.
Nitrates are commonly used in the therapy of congestive heart failure (CHF). They exert beneficial hemodynamic effects by decreasing left ventricular filling pressure and systemic vascular resistance while modestly improving cardiac output. The improvement in left ventricular function caused by nitrates is the result of combined reduction in outflow resistance and mitral regurgitation, while decreased pericardial constraint and subendocardial ischemia may also contribute to the process. With continuous nitrate administration, complete arterial tolerance develops, while venous tolerance appears to be only partial. The major mechanism of tolerance is loss of vascular smooth muscle sensitivity to nitrates. An increase in total blood volume occurring during the first few hours of an acute administration may partly contribute to tolerance. The importance of reflex neurohumoral activation is controversial; although it may contribute to tolerance in CHF, its role does not appear to be major. Chronic continuous nitrate therapy in CHF improves submaximal and maximal exercise tolerance. In combination therapy with hydralazine, isosorbide dinitrate reduces mortality, although to a lesser extent than the angiotensin converting enzyme inhibitor enalapril. Intravenous or sublingual nitrates are first-line agents in the therapy of acute pulmonary edema. In severe CHF, refractory to standard medical therapy, a short course of intravenous nitroglycerin, with or without inotropic agents, can help break the vicious spiral of CHF. Because tolerance occurs without nitrate-free intervals and until an optimal schedule of administration is determined, it makes good sense to include a nightly nitrate-free interval when prescribing nitrates for CHF in order to maintain maximal benefit during the hours of activity.
The single-bolus multiple-indicator-dilution technique was used to evaluate pulmonary removal of tracer 125I-labeled endothelin-1 in seven anesthetized dogs. Simultaneously, pulmonary arterial and aortic blood samples were obtained and assayed to determine the levels of immunoreactive endothelin-1. When 125I-endothelin-1 was compared with a plasma vascular reference (Evans blue dye), there was a single passage mean extraction of 31 +/- 8%. In contrast, there was no significant difference between immunoreactive endothelin-1 levels measured in blood samples from the pulmonary artery and the aorta (1.26 +/- 0.58 and 1.37 +/- 0.50 pg/ml, respectively; P = 0.47). The absence of an arteriovenous difference for bulk endothelin-1 across the lungs in the presence of tracer data indicating a substantial uptake implies that an amount of endothelin-1 quantitatively more or less equal to that removed is produced by the lung. The shapes of the dilution curves suggest that the tracer endothelin uptake by the lung is a one-way process without vascular reentry of tracer. We conclude that the dog lung is an important site for both uptake and release of endothelin-1.
Neuropeptide Y (NPY) is thought to be co-released with catecholamines in response to major cardiovascular stresses, but its relation to the release of catecholamines in response to minor stresses has been less well described. We therefore studied the response of plasma NPY-like immunoreactivity (NPY-Li) levels to standing (10 min) in eight normal subjects and 11 patients with congestive heart failure, and to short-term (6h) vasodilator therapy in 13 patients with congestive heart failure. In both normal and heart failure patients, NPY-Li-decreased (296 +/- 73 to 233 +/- 63 pg.ml-1 and 652 +/- 36 to 516 +/- 25 pg.ml-1 (P < 0.01) respectively) in response to standing, whereas catecholamines increased in both groups (norepinephrine 203 +/- 73 to 507 +/- 165 pg.ml-1 and 493 +/- 197 to 813 +/- 336 pg.ml-1 (P < 0.001) respectively and epinephrine 23 +/- 12 to 38 +/- 12 pg.ml-1 and 46 +/- 19 to 62 +/- 28 pg.ml-1 (P < 0.001) respectively). Both basal circulating NPY-Li and catecholamine levels were markedly increased in congestive heart failure patients, but catecholamines and NPY-Li did not correlate with each other. After 6 h of nitroglycerin infusion, mean arterial pressure was decreased, but circulating neurohumoral levels remained unchanged and NPY-Li levels decreased (653 +/- 37 to 517 +/- 26 pg.ml-1, P < 0.01). It is concluded that basal circulating NPY-Li and catecholamine levels are increased in congestive heart failure and that this neurohormone could play a concomitant role in the increase in peripheral resistance in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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The efficacy of lansoprazole (30 mg/d) and omeprazole (20 mg/d) has been assessed in active duodenal ulcer disease in 144 patients included in a multicentric, randomized, double-blind trial. After two weeks, the healing rates were 74% and 58% in the lansoprazole and omeprazole groups, respectively (P = 0.049). After 4 weeks, the healing rates were 94% in each group (NS). The delay to pain relief was 2 days for lansoprazole and 3 days for omeprazole (NS). Minor side effects occurred in 12% of the lansoprazole treated patients and in 13% of the omeprazole treated patients. No severe adverse events were reported. A slight increase in serum gastrin level was observed, similar in both groups (+35 UI/L and +19 UI/L for lansoprazole and omeprazole respectively). This study confirms previous results concerning the efficacy of both treatments in duodenal ulcer disease. The statistical difference observed for healing rates after 2 weeks could correspond to a faster efficacy for lansoprazole (30 mg) than for omeprazole (20 mg).
We examined exercise-induced changes in indicator-dilution estimates of the angiotensin-converting enzyme first-order kinetic parameter, the ratio of a normalized maximal enzymatic conversion rate to the Michaelis constant (Amax/Km), which, under stable enzymatic conditions, will vary with the pulmonary vascular surface area accessible to vascular substrate, the extravascular lung water (an index of the proportion of lung tissue perfused), and the central blood volume (from pulmonary trunk to aorta). Experiments were performed in 10 mongrel dogs at rest and through two increasing levels of treadmill exercise, with the use of two vascular space tracers (labeled erythrocytes and albumin), a water space tracer ([1,8-14C]-octanediol), and a vascular endothelium surface area marker, benzoyl-Phe-Gly-Pro ([3H]BPGP), which is a pharmacologically inactive angiotensin-converting enzyme substrate. The exercise-induced increase in cardiac output was accompanied by a linear increase in central blood volume, and dilutional extravascular lung water rapidly increased to an asymptotic proportion close to 100% of postmortem vascular lung water. There was an average 55% [3H]BPGP hydrolysis, which did not vary with flow, and the computed Amax/Km increased linearly with exercise. We conclude that exercise results in complete lung tissue recruitment and increases the pulmonary vascular surface area available for BPGP hydrolysis linearly with flow, so that pulmonary vascular recruitment continues after full tissue recruitment.
Eighty one women with vertebral osteoporosis were treated for up to 2 years with fluoride administered either as monofluorophosphate (MFP, 200 mg/day, i.e., 26.4 mg fluoride-ion) or sodium fluoride (NaF, 50 mg/day, i.e., 22.6 mg fluoride-ion). All patients received calcium supplementation (1 g of Ca2+/day) taken apart from NaF and in the same tablet for MFP. Despite almost similar fluoride dosage of both regimens, the early increase in the bone mineral density (BMD) of the lumbar spine was higher with MFP than with NaF, reaching 11% and 4%, respectively, at 1 year (p = 0.007), and 21% and 6%, respectively, at 18 months (p less than 0.001). The incidence of lower extremity pain syndrome related to benign stress microfractures was also higher with MFP than with NaF (35% and 15%, respectively, p less than 0.01). Urinary fluoride levels were higher in the MFP than in the NaF group (9.6 +/- 3.5 vs. 6.8 +/- 3.4 at one year, p = 0.003), suggesting that this difference in efficacy and tolerance is related to a better bioavailability of fluoride provided by MFP than by NaF. The occurrence of a stress microfracture could not be predicted by any clinical, biochemical, or densitometric parameter before treatment, but patients presenting with a stress microfracture during the course of the treatment had a higher gain in bone mass than those without stress fractures (at 1 yr+11 vs. +5%, p = 0.03 and at 18 months +18 vs. +6.9%, p less than 0.02). In conclusion, there is a clear correlation between the efficacy and the occurrence of side effects of fluoride therapy in osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine whether a 72-hour infusion of nitroglycerin produces hemodynamic improvement in patients with severe congestive heart failure and to assess the contributing role of various possible causes of hemodynamic tolerance to nitroglycerin, 19 patients received an infusion of nitroglycerin 1.5 micrograms/kg/min for 72 hours. In a subgroup of patients (n = 10), there was an increase in stroke work index and a decrease in ventricular filling pressures throughout the infusion and even after it was discontinued. Tolerance to the hemodynamic effects of nitroglycerin was partially reversed 8 hours after the infusion was stopped. Neurohumoral changes occurred but appeared to play only a minor role in the development of nitroglycerin tolerance. However, hematocrit fell 9 +/- 5%, which suggests that an increased intravascular volume contributed to tolerance. In summary: (1) a 72-hour infusion of nitroglycerin improves ventricular function in some patients with severe heart failure; (2) volume shifts from the extravascular to the intravascular compartments may, at least in part, be responsible for nitroglycerin tolerance; and (3) reflex neurohumoral activation may also play a small role in nitrate tolerance.
To better understand the mechanism of nitrate tolerance in patients with congestive heart failure, 13 patients received a 24 h infusion of nitroglycerin (1.5 micrograms/kg body weight per min) with or without N-acetylcysteine (225 mg/kg per 24 h). The infusions were separated by a 24 h nitrate-free interval. By the end of the nitroglycerin infusion, mean arterial pressure had returned to baseline values and there was a significant increase in ventricular filling pressures and systemic vascular resistance compared with values after 1 h of treatment. The simultaneous infusion of N-acetylcysteine had no effect on these changes. Although a strict fluid restriction of 1.5 liters/day was maintained for 1 week before and throughout the study, after 24 h of nitroglycerin infusion there was a significant and similar degree of hemodilution whether nitroglycerin was infused alone (9.1 +/- 4.3%) or with N-acetylcysteine (8.7 +/- 4.1%). This hemodilution corresponded to an increase in intravascular volume of 745 +/- 382 ml, most of which occurred during the 1st h. Plasma renin activity increased and plasma atrial natriuretic peptide decreased during the infusion. The results of this study suggest that nitrate tolerance is multifactorial. In addition to the previously described pharmacologic tolerance to the effect of nitroglycerin on vascular smooth muscle, a capillary fluid shift from the extravascular to intravascular space appears to be involved, especially during the 1st h of the infusion. A third mechanism, reflex neurohumoral activation, also seems to contribute to the genesis of nitroglycerin tolerance.
We used the multiple indicator-dilution technique with norepinephrine, a vascular endothelium surface marker, to study the pulmonary vascular changes in awake exercising dogs. The vascular space tracers, labeled erythrocytes and albumin, and a water space tracer, 1,8-octanediol, were injected with the norepinephrine, and right atrium-aortic root dilution curves were obtained in nine dogs, at rest and at two increasing levels of exercise. Extravascular lung water multiple tracer dilutional estimates increased with flow and rapidly approached a maximal asymptotic value representing 75% of the postmortem lung weight. The ratio of the extravascular lung water measured in this way to that measured gravimetrically also increased, to reach an asymptotic proportion of close to 100%. The transit time-defined central vascular space increased linearly with flow; the ratio of lung tissue space to lung vascular space, therefore, decreased with increasing flow. The mean tracer upslope norepinephrine extractions at rest and at the two levels of exercise were 17 +/- 1.2, 14 +/- 0.8, and 15 +/- 0.8% (SE). With the use of the Crone approximation, we computed permeability-surface area products for norepinephrine; these increased linearly with flow. If permeability does not change, the increase in the permeability-surface area product with flow can be attributed to capillary recruitment. We conclude that when all lung tissue has become accessible to 1,8-octanediol delivered via the perfused vascular space, there is nevertheless further recruitment, with increase in flow, of vascular surface that can extract norepinephrine.
Tolerance to the continuous intravenous infusion of nitroglycerin is thought to be largely the result of a decrease in vascular responsiveness, possibly due to intra-smooth muscle sulfhydryl group depletion. Another mechanism proposed to contribute to tolerance is nitroglycerin-induced reflex neurohumoral activation resulting in vasoconstriction and sodium and water retention. It has been proposed that the sulfhydryl group-containing angiotensin converting enzyme (ACE) inhibitor captopril may be useful in preventing tolerance to nitroglycerin by repleting sulfhydryl groups and by decreasing reflex neurohumoral activation. However, by decreasing renal perfusion pressure, the combination of captopril and nitrates could also lead to renal dysfunction. The objectives of this study were to determine whether captopril prevented or significantly reduced hemodynamic tolerance to a 72 h infusion of nitroglycerin, and to determine whether the combination of nitroglycerin and captopril caused deterioration of renal function. Nineteen patients with congestive heart failure received nitroglycerin (1.5 micrograms/kg/min) alone (n = 11) or in combination with oral captopril (63 +/- 8 mg/day) (n = 8). In both groups, partial hemodynamic tolerance developed within the first 24 h of nitroglycerin infusion. Nitroglycerin therapy, with or without captopril, did not affect plasma adrenaline, noradrenaline, aldosterone or arginine vasopressin. However, plasma renin activity increased and atrial natriuretic peptide decreased in both groups, these changes being significant after 1 h of infusion but gradually returning towards baseline, in both groups, over the next 71 h. The nitroglycerin infusion did not alter body weight, urine output, creatinine clearance or fractional sodium excretion in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
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