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Biomedical subjects

S Fernandez

Publications and source records attributed to S Fernandez.

At least 19 recordsLinked to original sources

Isoproterenol-dependent decrease in oxygen uptake and respiratory enzyme activities in rat myocardial tissue and mitochondria.

OBJECTIVE: Myocardial damage induced by isoproterenol is believed to be secondary to increased oxygen demands on the heart. Our objective was to test an additional primary action of isoproterenol on tissue and mitochondrial oxidative metabolism and to compare these effects with the effects of other adrenergic agents in the presence of adrenergic inhibitors. DESIGN: Prospective, dose-response study. SETTING: Research laboratory at a university hospital. SUBJECTS: Fifty Sprague-Dawley female rats (200 to 350 g), slightly anesthetized with ether and divided into several groups. INTERVENTIONS: In 26 rats, the heart was removed, cut into fine slices (0.5-mm thickness), and placed in an ice-cold buffer. In 22 animals, the hearts were perfused in the Langendorff manner and chopped and processed for mitochondrial studies. MEASUREMENTS AND MAIN RESULTS: We determined the following: a) the direct "in vitro" effects of isoproterenol and related catecholamines on normal oxygen uptake using myocardial slices; b) rat heart oxygen consumption and mitochondrial oxygen uptake from isolated organs, perfused with isoproterenol; c) measurements of enzyme activities in submitochondrial particles from the same perfused hearts; and d) the direct effects of isoproterenol on normal mitochondria isolated from normal nonperfused hearts. The oxygen uptake was determined polarographically with a Clark-type electrode and enzymatic activities were assayed by spectrophotometric reduction of cytochrome c at 550 nm with different mitochondrial substrates. Isoproterenol (0.01 to 100 nM) decreased the oxygen uptake by the heart slices in a dose-dependent manner. In comparison, epinephrine or norepinephrine per se did not change the parameter. However, with the addition of alpha-adrenergic receptor inhibitors, oxygen uptake decreased to values similar to those values obtained with isoproterenol. Also, mitochondria isolated from hearts perfused with isoproterenol had decreased state 3 respiratory rates (by 50%) and decreased respiratory control ratios (by 30%), without changes in adenosine 5'-diphosphate/oxygen ratios. The respiratory chain enzyme activities were also lowered. CONCLUSIONS: The data suggest that while isoproterenol increases "in vivo" oxygen uptake by the working rat heart, isoproterenol can simultaneously decrease maximal adenosine 5'-diphosphate-induced mitochondrial oxygen uptake and in vitro myocardial tissue oxygen uptake, probably by modifying the mitochondrial respiratory enzymes. This action could be counteracted by alpha-adrenergic agonist effects.

Animals

Iliopsoas compartment: normal anatomy and pathologic processes.

The iliopsoas compartment is an extraperitoneal space that contains the greater psoas, smaller psoas, and iliac muscles. Many pathologic processes may involve the iliopsoas compartment, including inflammatory, hemorrhagic, and neoplastic conditions. Psoas muscle infection is usually due to direct extension from contiguous structures. With the decreasing incidence of tuberculosis, the majority of psoas abscesses now encountered have a pyogenic origin. Hemorrhage into the psoas muscle can be spontaneous or secondary to various conditions. Neoplastic involvement of the psoas muscle is usually due to contiguous spread and is rarely primary. With the refinement of imaging modalities, there has been increased recognition of diseases that involve the iliopsoas compartment. Although these conditions may look similar radiologically, they can be correctly diagnosed by combining the radiologic findings with the clinical history. Biopsy is effective in diagnosis of such conditions; aspiration and drainage are effective in both diagnosis and therapy.

Abscess

Liver oxygen uptake dependence and mitochondrial function in septic rats.

Defective oxygen consumption and a pathological dependence of oxygen uptake on O2 supply have been considered important events in sepsis. To relate these features with tissue and mitochondrial metabolism, we studied oxygen uptake in whole isolated and perfused rat liver at two O2 supply levels, in the same liver slices, and in isolated liver mitochondria. Experimental sepsis in rats was induced by cecal ligation and double-gauge puncture. The results showed that liver and tissue slices from septic animals had a 60% greater O2 uptake than that of controls and that, during sepsis, liver O2 uptake was markedly dependent on O2 supply. Concomitantly, mitochondrial O2 uptake was nearly 30% greater with malate-glutamate as substrate, but not with succinate; lowering O2 concentration in the medium did not alter the enhanced function. In submitochondrial, only NADH-dehydrogenase activity was 100% higher in septic samples. At least, in some tissues, O2 dependence is a function of O2 availability, sensitized by increased mitochondrial O2 uptake related to changes in respiratory enzymes.

Adenosine Diphosphate

Intolerance to piroxicam in patients with adverse reactions to nonsteroidal antiinflammatory drugs.

To evaluate the tolerance to piroxicam in patients with urticaria induced by analgesic and/or nonsteroidal antiinflammatory drugs (NSAIDs), we carried out a 2-year study in an outpatient clinic. All the patients referred to the clinic for study entered a protocol for evaluation of intolerance to one or more drugs. If patients were allergic to at least two different NSAIDs they were allocated to group A, but if patients were allergic to only one they were considered as having selective intolerance (group B). Either piroxicam or placebo was administered under controlled conditions to both groups. In group A, five out of 18 patients had a positive response to piroxicam. In group B, in all the 25 cases studied a good tolerance to piroxicam was shown. These results indicate that in the group with intolerance to NSAIDs piroxicam induced a positive reaction in 27% of the cases, and that this drug should be administered with caution and with a previous controlled challenge in this type of patient. Piroxicam was well tolerated in the group with selective intolerance, indicating that mechanisms other than interference with the prostaglandin synthesis and release of inflammatory mediators participate in allergic reactions to NSAIDs.

Acetaminophen

Specific IgE antibodies to vespids in the course of immunotherapy with Vespula germanica administered to patients sensitized to Polistes dominulus.

Sera from a group of 12 patients with anaphylactic reactions to vespids were studied. Field observations and RAST values suggested that the offending insect was Polistes dominulus (PD). Specific IgE antibodies to PD appeared in all cases and to Vespula germanica (VG) in nine. Absorption studies in these basal sera showed that IgE antibodies to VG were due to cross-reactivity with PD. The RAST value to both venoms was higher after immunotherapy (IT) in six cases. IgE antibodies increased to determinants common to both vespids, and in 41% of the cases to specific epitopes of VG venom allergens not initially detected in the basal sera. In one case antibodies increased only to VG without a corresponding rise to PD. These results indicate that if the correct venom to which the individuals are sensitized is not administered IgE antibodies may appear which were not initially detected in the patients' sera. The levels of these antibodies declined during the course of IT.

Adult

Gastric mucosal pH as a prognostic index of mortality in critically ill patients.

OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU.

Critical Care

Oral alterations in Steinert's myotonic dystrophy: a presentation of two cases.

Two patients with Steinert's myotonic dystrophy are presented. The disease was suspected because of alterations in orofacial musculature clinically manifest as difficulties in swallowing, mastication, and speech, and as occlusal anomalies and maxillary bone deformities. The presumed diagnosis was reached as a result of the presence of percussion myotonia of the tongue; confirmation was based on family antecedents, electromyographic alterations, and muscle histopathologic findings.

Adolescent

Ultrasound evaluation of the distal femoral epiphyseal ossification center as a screening test for intrauterine growth retardation.

In a heterogeneous group of 226 pregnant women, a retrospective study was done of the relation between the distal femoral epiphyseal ossification center detected by ultrasound and the birth weights of the infants. The ossification center of the femur was detectable in 202 of the 208 infants appropriate for gestational age; it was undetectable in 15 of the 18 infants small for gestational age. Because our results compared favorably with those reached by more complicated methods in the literature, we propose that the distal femoral epiphyseal ossification center be used as a screening test for intrauterine growth retardation.

Birth Weight

Vaccination of newborns of HBsAg-positive carrier mothers with a recombinant DNA hepatitis B vaccine.

Thirty neonates born to HBsAg-positive mothers were vaccinated with a 20 microgram dose of the SmithKline Biologicals recombinant DNA yeast-derived vaccine within 24 hours after birth, with similar inoculations repeated 1 and 2 months later. Preliminary results indicate that the recombinant vaccine was well tolerated and immunogenic. A 100% seroconversion rate was achieved 4 months after the first vaccine dose and the anti-HBs geometric mean titres progressively rose from 14 to 31,279 and 361 IU/l at months 1, 2, 4, and 6, respectively. Although a longer period of observation and comparison with a historical control group are needed to evaluate its protective efficacy in this high-risk population, the fact that no vaccinated newborns have been infected is encouraging.

Antigens

Metabolism of the phospholipid precursor inositol and its relationship to growth and viability in the natural auxotroph Schizosaccharomyces pombe.

Phospholipid metabolism in the fission yeast Schizosaccharomyces pombe was examined. Three enzymes of phospholipid biosynthesis, cytidine diphosphate diacylglycerol synthase (CDP-DG), phosphatidylinositol (PI) synthase, and phosphatidylserine (PS) synthase, were characterized in extracts of S. pombe cells. Contrary to an earlier report, we were able to demonstrate that CDP-DG served as a precursor for PI and PS biosynthesis in S. pombe. S. pombe is naturally auxotrophic for the phospholipid precursor inositol. We found that S. pombe was much more resistant to loss of viability during inositol starvation than artificially generated inositol auxotrophs of Saccharomyces cerevisiae. The phospholipid composition of S. pombe cells grown in inositol-rich medium (50 microM) was similar to that of S. cerevisiae cells grown under similar conditions. However, growth of S. pombe at low inositol concentrations (below 30 microM) affected the ratio of the anionic phospholipids PI and PS, while the relative proportions of other glycerophospholipids remained unchanged. During inositol starvation, the rate of PI synthesis decreased rapidly, and there was a concomitant increase in the rate of PS synthesis. Phosphatidic acid and CDP-DG, which are precursors to these phospholipids, also increased when PI synthesis was blocked by lack of exogenous inositol. The major product of turnover of inositol-containing phospholipids in S. pombe was found to be free inositol, which accumulated in the medium and could be reused by the cell.

CDP-Diacylglycerol-Inositol 3-Phosphatidyltransfer

Characterization of a sexual steroid binding protein in Bufo arenarum.

Reproductively active female Bufo arenarum possess a serum protein (SBP) that binds testosterone, dihydrotestosterone, and estradiol with high affinity and capacity. The binding capacity values are two orders of magnitude higher than those found in human serum. The specificity of B. arenarum SBP is comparable to human SBP with the exception that it has a high affinity for the synthetic androgen methyltrienolone (R1881). The physicochemical characterization of SBP indicates a Stokes radius of 43.5 A, a sedimentation coefficient of 5.2 S, and a molecular weight of 93,300.

Animals

Influence of undernutrition during gestation and suckling on development and sexual maturity in the rat.

The effects of undernourishment during gestation and suckling on rats subsequently fed ad libitum for 4 mo after weaning are explored. We measured the following: weight at birth and over a 5-mo period; sexual behavior of adult males; curiosity; basal physical activity; morphometric measures; organ weights (absolute and relative) including brain, testicles and seminal vesicles in males 5 mo of age; and the O2 uptake of some brain and glandular structures in males at 5 mo of age. Body weight of the malnourished animals was consistently lower than that of the controls. Compared to controls sexual behavior in undernourished males was significantly reduced, while curiosity test and basal physical activity were increased. The absolute weights of all organs (except the pituitary gland) were significantly lower in malnourished males at 5 mo than in controls. Compared to controls, relative weight of brain was greater and that of seminal vesicles was less in the male rats. Oxygen uptake was significantly lower in the pituitary gland and testicles of malnourished males than of controls. In view of these results, it can be concluded that malnutrition in utero and while suckling affects fundamental parameters of both development and reproductive function in the male offspring 4 mo after feeding ad libitum is begun at weaning.

Animals

Rapid loss of delta-aminolevulinic acid dehydratase activity in primary cultures of adult rat hepatocytes: a new model of zinc deficiency.

Nonproliferating cultures of adult rat hepatocytes were found to lose 60-70% of cell-associated zinc during their first 24 h of incubation in standard, serum-free medium. The loss of zinc was accompanied by a profound loss (greater than 95%) in the activity of the zinc metalloenzyme, delta-aminolevulinic acid dehydratase, as well as a loss (greater than 85%) in the cellular content of immunoreactive delta-aminolevulinic acid dehydratase protein. Restoration of cellular zinc content by the addition of zinc to the culture medium partially prevented the losses of both delta-aminolevulinic acid dehydratase activity and immunoreactive protein. Since the spontaneous, selective loss of cellular zinc appears to have specific effects on a relevant hepatic function, this culture system constitutes a novel in vitro model of zinc deficiency in mature liver.

Animals

Effect of early pre- and postnatal acquired malnutrition on development and sexual behavior in the rat.

In this paper we attempt to elucidate the effects on the rat offspring of undernourishment during pregnancy and lactation on the following parameters were examined: weight at birth and its evolution over a three-month period, sexual behavior of adult males, vaginal opening and sexual cycle of females, blood sugar, blood proteins, hematocrit, natremia, potassemia, body weight and weight of testicles, seminal vesicles and adrenal glands in males 5 months of age. Our results indicate highly significant decreases in body weight in experimental animals over a period of three months. Vaginal opening in experimental females is significantly delayed and their estrous cycle is shortened. Male sexual behavior shows decreases in neuromotor activity and prolongation of the refractory period in experimental male animals. Of the parameters monitored at 5 months of age, only blood sugar levels were significant decreased in experimental male rats. In view of these results, it can be concluded that in utero and lactation period malnutrition affects fundamental parameters of both development and reproductive function in the offspring.

Adrenal Glands

Bleomycin inhibits hepatic mixed function oxidation.

Bleomycin inhibits hepatic microsomal ethylmorphine N-demethylase activity in both the athymic (nude) mouse and the rat four days after a single injection. This inhibition occurred both with subcutaneous and intraperitoneal injections. With multiple dose chronic treatment, s.c. injections resulted in decreases in both enzymatic activity and cytochrome P450 concentration in both species. However, i.p. chronic injection resulted in decreases only in the rat.

Animals