Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise

BACKGROUND: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. METHODS AND RESULTS: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. CONCLUSIONS: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.     

Evaluation of fecal technics for the diagnosis of cat liver fluke infection

The comparative efficiency of 5 standard technics for the detection of feline liver fluke ova in feces was evaluated. The formalin-ether technic proved superior to direct smear, sugar flotation, zinc sulfate flotation, or detergent sedimentation technics. The formalin-ether technic correctly diagnosed all Platynosomum concinnum-infected cats studied, as confirmed by necropsy findings.     

The species specificity of fish and mammalian gonadotropic hormones

Protein spectra of the hypophyses of fishes from various taxonomic groups obtained by disc electrophoresis in polyacrylamide gel exhibit high species specificity. By means of biological testing on the loach Misgurnus fossilis, zones of gonadotropic activity were obtained which differ in various species by the electrophoretic mobility. The mammalian gonadotropins obtained reveal lower electrophoretic mobility. The gonadotropins investigated significantly differ in their biological effect.     

Functional analysis of the fibrinogen-related scabrous gene from Drosophila melanogaster identifies potential effector and stimulatory protein domains

The scabrous (sca) gene encodes a secreted dimeric glycoprotein with putative coiled-coil domains N-terminally and a C-terminal region related to the blood clot protein fibrinogen. Homozygous sca mutants have extra bristle organs and rough eyes. We describe a GAL4-based expression system for testing rescue of the sca mutant phenotype by altered SCA proteins and for misexpression. We find that deletion of the fibrinogen-related domain (FReD) greatly decreases SCA function, confirming the importance of this conserved region. SCA function could not be restored by FReDs from human fibrinogen chain genes. However, proteins lacking any FReD still showed some function in both rescue and misexpression experiments, suggesting that putative effector-binding regions lie outside this domain. Consistent with this, proteins expressing only the FReD had no rescuing activity but were recessive negative; i.e., they enhanced the phenotype of sca mutations but had no phenotype in the presence of a wild-type sca allele. This suggests that the FReD contributes to SCA function by binding to other components of the bristle determination pathway, increasing the activity of the linked N-terminal region.     

Study of the photochemical behaviour of sunscreens – benzylidene camphor and derivatives

Benzylidene camphor derivatives have been currently used as ultraviolet filters in sunscreen compositions. When solutions of these compounds are exposed to the light from a solar simulator, a photoinduced cis-trans isomerization is observed. The initial quantum yields of this photochemical isomerization of studied molecules have been determined in several solvents. Their photochemical behaviour depends neither on the concentration nor on the presence or absence of oxygen or other inhibitors such as isopropanol or biacetyl. It means that the lifetime of the precursor states of isomerization is about 10⁻¹²s, that is to say, too short for them to react with neighbouring molecules.
For each compound, the ratio     of the respective concentrations of 'E' and 'Z' forms was also determined by photostationary state. A good agreement between theoretical and experimental values of this ratio shows that the studied compounds are only very slightly photodegradable. This was confirmed by the low values of photodegradation quantum yields.
In case of the studied compounds, the isomerization process observed is totally reversible. During irradiation a photostationary state is quickly reached, each isomer may change into the other form after absorption of a photon which leads to a mixture of isomers. In practice, it is this mixture of E and Z forms which acts as UV filters.
It may be said that a very short lifetime of the excited states, a good light stability and a reaction inertia under light irradiation make these compounds excellent sunscreen agents.
Comportement photochimique des antisolaires. Benzylidène camphre et certans de ses dérivés     

A test of the practical value of estimating breath sound intensity. Breath sounds related to measured ventilatory function

An acromegalic patient with galactorrhea-amenorrhea who conceived following long-term 2-bromo-alpha-ergocryptine (CB-154) therapy is described. During CB-154 therapy, determinations of serum prolactin (PRL), luteinizing hormone (LH)-human chorionic gonadotropin, follicle-stimulating hormone a reduction in PRL level followed by an LH peak, a rise in basal body temperature and menstruation. The patient became pregnant during the next cycle, but therapeutic abortion was performed because of the active acromegaly. These results demonstrate that CB-154 can restore ovulatory function not only to the patient with a hypothalamic disorder but also to the acromegalic patient with an enlarged sella turcica.     

Malignant tumors of the pleura in the post-pneumothoracic cavities

The single nephron glomerular filtration rate (SNGFR) was determined in superficial (S) and juxtamedullary (JM) nephrons of 10 anesthetized rabbits by the 14C ferrocyanide infusion technique. The length of the proximal tubules and the volume of the glomeruli were also determined for the same nephrons. SNGFR was higher in JM than in S: 28.6 +/- 3.4 versus 22.6 +/- 3.0 nl/min, P less than 0.001. In JM nephrons, glomeruli were larger than in S: 1.3 +/- 0.1 versus 0.9 +/- 0.1 nl, P less than 0.001, whereas there was no difference between proximal tubule length in either category (s, 8.7 +/- 0.3 and JM, 8.9 +/- 0.5 mm). In 6 out of 8 animals, SNGFR was significantly correlated to glomerular volume. Lack of correlation was observed between SNGFR and length of proximal tubule in all animals but one. These results show that the rabbit, as well as small rodents and the dog, has a higher SNGFR in juxtamedullary than superficial glomeruli. Although this functional difference is not related to the length of the proximal tubule in each individual animal, the ratio between the mean SNGFR value and the mean length of the proximal tubule in superficial rabbit nephrons is similar to the ratio found in other species.     

Antagonism by locally applied dopamine into the nucleus accumbens or the corpus striatum of alpha-methyltyrosine-induced disruption of conditioned avoidance behaviour

Male Sprague-Dawley rats were trained to avoid an electric shock in a two-way shuttle-box. The local application of dopamine into the nucleus accumbens or the corpus striatum was found to antagonize the suppression of conditioned avoidance behaviour induced by systemically administered alpha-methyltyrosine, emphasizing the importance of these dopamine-rich brain structures in mediating conditioned avoidance behaviour.