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Biomedical subjects

J Garcia

Publications and source records attributed to J Garcia.

At least 253 records · Page 14Linked to original sources

The effects of aging on the electrophysiologic and hemodynamic responses to nifedipine in isolated perfused hearts.

Age effects on responses to calcium channel blockade with nifedipine were studied in isolated Langendorff-perfused Fischer 344 rat hearts. Responses to 25 min of perfusion with nifedipine concentrations of 0, 25, 50, 75, and 100 ng/ml were studied in hearts from 11 mature (6 months) and 13 senescent (23-27 months) male F344 rats. Nifedipine produced significant increases in the atrial cycle length (p less than 0.001), paced atrioventricular (AV) conduction time (p less than 0.001), AV Wenckebach cycle length (p less than 0.001), left ventricular (LV) diastolic pressure (p less than 0.001), and decreases in LV systolic pressure (p less than 0.001) and peak dP/dt (p less than 0.001) in hearts from both mature and senescent rats. Greater decreases in the atrial rate (p less than 0.05) and depression of peak dP/dt (p less than 0.05) were detected in senescent vs. mature rat hearts. No age difference in responses of AV conduction parameters were detected although increases in the AV Wenckebach cycle length appeared to be greater in senescent hearts at concentrations greater than 75 ng/ml.

Aging↗

Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo.

BACKGROUND: The functional impairment of persistently ischemic, or "hibernating," myocardium may serve to maintain myocardial cell viability through a reduction of energy requirements. Although previous studies have, in a variety of experimental models, independently shown variable responses in lactate metabolism and intracellular phosphates during prolonged ischemia, the responses of these metabolites under identical flow conditions have not been adequately described. METHODS AND RESULTS: To examine the responses of high-energy phosphates and lactate metabolism to prolonged ischemia induced by partial coronary artery stenosis, 12 open-chest pigs were studied using 31P nuclear magnetic resonance spectroscopy. Concurrent measurements of blood flow, segment shortening, high-energy phosphates, and lactate release (in nine animals) were made during 2 hours of regional ischemia. Subendocardial blood flow and segment shortening were persistently depressed during ischemia, with parallel reductions in ATP, phosphocreatine (PCr), and the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Pi was persistently elevated during the ischemic period. In contrast, lactate release increased significantly from 0.23 +/- 0.04 to 1.34 +/- 0.28 mumol/ml after 15 minutes of ischemia (p less than 0.05) but then decreased to 0.73 +/- 0.17 mumol/ml at 2 hours (p less than 0.05 versus 15 minutes, p = NS versus control). Similarly, pH increased significantly from a nadir of 6.82 +/- 0.07 at 30 minutes of ischemia to 6.98 +/- 0.05 at 2 hours. CONCLUSIONS: Changes in high-energy phosphates parallel changes in blood flow and function during prolonged ischemia, whereas there is a partial amelioration in lactate production and acidosis. These data support the concept that reduction of myocardial energy requirements during prolonged flow reduction results in signs of reduced ischemia.

Animals↗

Energetics of acute pressure overload of the porcine right ventricle. In vivo 31P nuclear magnetic resonance.

In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of the right ventricular (RV) free wall was employed to determine (a) whether phosphorus energy metabolites vary reciprocally with workload in the RV and (b) the mechanisms that limit RV contractile function in acute pressure overload. In 20 open-chest pigs, phosphocreatine (PCr)/ATP ratio (an index of energy metabolism inversely related to free ADP concentration), myocardial blood flow (microspheres), and segment shortening (sonomicrometry, n = 14) were measured at control (RV systolic pressure 31 +/- 1 mm Hg), and with pulmonary artery constriction to produce moderate pressure overload (RV systolic pressure 45 +/- 1 mm Hg), and maximal pressure overload before overt RV failure and systemic hypotension (RV systolic pressure 60 +/- 1 mm Hg). With moderate pressure overload, PCr/ATP declined to 89% of control (P = 0.01), while contractile function increased. Adenosine (n = 10, mean dose 0.16 mg/kg-min) increased RV blood flow by an additional 41% without increasing PCr/ATP, indicating that coronary reserve was not depleted and that the decrease in PCr/ATP from control was not due to ischemia. With maximal pressure overload and incipient RV failure, PCr/ATP fell further to 81% of control and RV blood flow did not increase further, even with adenosine. Thus: (a) The decline in PCr/ATP with moderate RV pressure overload, without evident ischemia or contractile dysfunction, supports the positive regulation of oxidative phosphorylation by ATP hydrolysis products. (b) Depletion of RV coronary flow reserve accompanies the onset of RV failure at maximal pressure overload.

Adenosine Triphosphate↗

High-dose chemotherapy with bone marrow rescue for treatment of Hodgkin's disease.

Between December 1st 1984 and July 1st 1991, 20 patients, 11 males and 9 females, median age 36 years (range 14-54) with Hodgkin's disease were treated with high dose chemo-radiotherapy followed by autologous bone marrow rescue. At the time of autologous bone marrow transplantation, 8 patients were in complete remission, 9 in sensitive relapse and 3 were resistant to conventional treatments. There were 3 early procedure-related deaths: 1 cardiac failure due to cyclophosphamide treatment, 1 veno-occlusive disease, and 1 patient died from CMV interstitial pneumonitis, 4 months after ABMT. Of the 17 other patients, 15 are alive, 12 in complete remission, 2 in relapse and 1 patient is not evaluable due to short-follow-up follow-up. Disease free survival is 65% at 20 months with a follow-up of 60 months. There is a trend for a better disease-free survival in patients in complete remission at the time of autologous bone marrow transplantation vs patients in sensitive relapse, although it does not reach statistical significance (80% vs 37%).

Adolescent↗

Muscle, tendon, and ligament evaluation.

Magnetic resonance imaging is the technique of choice for soft tissue evaluation. Muscle injuries occurring during physical activities are very frequent and are very well appreciated by MR imaging. Associated with 31P spectroscopy, MR imaging allows better understanding of physiopathologic phenomena and inflammatory lesions. An early and correct diagnosis is possible using MR imaging in cases of soft tissue pseudotumors, such as myositis ossificans. The quadriceps and Achilles tendons, which are superficial and thick, can be well evaluated using ultrasonography. Nevertheless, MR imaging is superior for deeply situated tendons and ligaments of the knee and ankle.

Athletic Injuries↗

Efficacy of once-a-day intranasal administration of triamcinolone acetonide in patients with seasonal allergic rhinitis.

A 4-week, double-blind, parallel group study compared the safety and efficacy of once-a-day intranasal administration of triamcinolone acetonide (Nasacort) versus placebo in 304 patients (155 adult and 149 adolescent) with seasonal allergic rhinitis. Patients were randomized to receive triamcinolone acetonide (110, 220, or 440 microgram) or placebo once daily each morning. Daily rhinitis symptoms scores, weekly patient and physician global assessments, and weekly nasal eosinophil smears were obtained. In each triamcinolone acetonide group, significant (P less than .05) improvement over placebo was noted in the nasal index (sum of ratings for stuffiness, discharge, and sneezing) by week 1, the first point of analysis, and maintained throughout the study. Triamcinolone acetonide groups also demonstrated significant (P less than .05) improvement over placebo in all individual rhinitis symptoms evaluated. The greatest improvement in symptoms was observed at the 440 microgram dose. A significant decrease in eosinophil counts paralleled clinical improvement in all triamcinolone acetonide groups. Physicians and patients rated triamcinolone acetonide significantly (P less than .05) more effective than placebo. Responses of adult and adolescent patients were comparable. Adverse experiences, clinical laboratory values, and results of physical examinations were unremarkable and comparable between the triamcinolone acetonide and placebo groups. We conclude that triamcinolone acetonide is safe, well tolerated, and superior to placebo as a once-a-day treatment for seasonal allergic rhinitis.

Administration, Intranasal↗

[Möbius syndrome and bilateral chorioretinal coloboma].

A child with palsy of the right facial nerve and bilateral palsy of the VIth, IXth and XIIth cranial nerves, dysfunction of the VIIIth cranial nerve, facial malformations and bilateral equinovarus was diagnosed on the basis of these features as having Moebius syndrome. Ocular studies disclosed congenital cataract and chorioretinal coloboma in both eyes. These ocular abnormalities have not previously been described in Moebius syndrome. This paper discusses whether the coexistence of these two types of anomalies may be due to occurrence of a break in the primitive internal carotid and trigeminal arteries between the fourth and fifth postconceptional weeks, causing maldevelopment of the choriocapillary and impairing neuron differentiation in cranial nerve nuclei.

Choroid↗

Increased concentrations of endogenous 13-cis- and all-trans-retinoic acids in diffuse idiopathic skeletal hyperostosis, as demonstrated by HPLC.

Endogenous 13-cis- and all-trans-retinoic acids have been quantitated in human serum using a solvent extraction procedure followed by isocratic reversed phase high performance liquid chromatography and UV detection. In healthy adults, after an overnight fasting period, the concentrations of 13-cis- and all-trans-retinoic acids yielded 5.3 +/- 2.43 nmol/l and 11.8 +/- 3.3 nmol/l, respectively (mean +/- SD). The method has been successfully applied to the analysis of both isomers in serum from patients with idiopathic skeletal hyperostosis in whom, the 13-cis- as well as all-trans-retinoic acid levels were raised as compared to the control group.

Adult↗

The effects of aging on the electrophysiologic responses to verapamil in isolated perfused rat hearts.

The effects of aging on heart rate and atrioventricular (AV) conduction responses to verapamil (0-100 ng/ml) were studied in Langendorff perfused hearts from 12 mature (4-6 months) and 12 senescent (24 months) male Fischer 344 rats and in hearts from 10 mature and 9 senescent rats after reserpine administration (0.25 mg/kg/day i.p. for 5-7 days). During 30 min of perfusion with verapamil concentrations of 0, 10, 20, 50 and 100 ng/ml in the absence of reserpine administration, intervals between atrial electrograms (A-A intervals), paced AV conduction time and AV Wenckebach cycle lengths increased in hearts from all animals (P less than .001). A-A intervals increased more in senescent vs. mature animals (with marked slowing in 3/12 senescent and 0/12 mature at 100 ng/ml), spontaneous AV Wenckebach block occurred more frequently in hearts from senescent animals (in 7/12 senescent and 1/12 mature, P less than .07) and AV Wenckebach cycle length increased more in senescent vs. mature hearts (from 123 +/- 11 to 294 +/- 108 msec, mean +/- S.D., in mature vs. 154 +/- 16 to 458 +/- 10 msec in senescent hearts). Reserpine administration did not significantly alter qualitative responses to verapamil, but accentuated age differences in responses at higher verapamil concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Porcine pancreas extract decreases blood-ionized calcium in mice and inhibits osteoclast formation and bone resorption in culture.

Patients with acute pancreatitis commonly manifest hypocalcemia for reasons which are unknown. We found that porcine pancreas extracts (PX) significantly decreased blood-ionized calcium in Balb/c mice. Partially-purified PX with a molecular mass of approximately 27 kDa decreased blood-ionized calcium in the mice. Partially-purified PX suppressed not only 45Ca release from fetal rat long bones which had been stimulated by parathyroid hormone, interleukin-1 alpha, tumor necrosis factor, transforming growth factor-alpha, 1,25-dihydroxyvitamin D3 and prostaglandin E2, but tartrate-resistant acid phosphatase-positive multinucleated cell formation in the presence of 1,25-dihydroxyvitamin D3 in mouse marrow cultures. The results suggest that there is an as yet-unidentified bone metabolism-regulating substance in porcine pancreas which might be responsible for the hypocalcemia associated with acute pancreatitis.

Animals↗

Limited sequence variation in human T-lymphotropic virus type 1 isolates from North American and African patients.

Nucleotide sequences were determined from the env genes of three HTLV-I clones derived from two North American patients and one African patient with adult T-cell leukemia/lymphoma (ATLL). In addition, sequences from the pX region, between env and the 3'LTR, were determined from one of these isolates. These data were compared to sequences derived from HTLV-I isolates of two Japanese ATLL patients, a Japanese patient with HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) and a Caribbean ATLL patient. Nucleotide sequence variation was found to be less than 6% in coding and noncoding regions. Predicted amino acid sequences varied between 0.6 and 1.8% in the envelope, 0-3.7% in rex, 0.8-2.5% in the tax gene product, and 3-14.0% in the pX-I open reading frame. Comparisons of the predicted amino acid sequences of the surface envelope protein (SU-gp46) suggest that the variation between isolates of different geographical origins is greater than that between isolates obtained from the same region of the world.

Africa↗

Formation of noninfectious HIV-1 virus particles lacking a full-length envelope protein.

Deletions were constructed within a functional human immunodeficiency virus type 1 (HIV-1) proviral clone in order to assess the role of the envelope protein in virus particle formation. A graded exonuclease deletion technique was used to produce 12 clones with deletions of 175-308 nucleotides in the first conserved domain of envelope. This included 9 clones with frameshift deletions and 3 clones with in-frame deletions. Isogenic pairs of env deletion clones were produced with or without an additional deletion in the vif and vpr genes. Upon transfection, all clones produced virus particles, as determined by p24 antigen, reverse transcriptase, and sucrose gradient assays with conditioned media. Virus particles produced from clones with deletions in env or vif and vpr, or both regions, banded on sucrose gradients with a mobility similar to that of virus produced by the parental clone. The p24 gag capsid protein in the particles was resistant to trypsin, but the particles were disrupted by treatment with Triton X-100, suggesting the presence of a surrounding lipid bilayer. Furthermore, electron microscopic studies revealed both mature and immature virus particles derived from COS cells transfected with the env deletion clones. Cocultivation experiments with lymphoid cells and cells transfected with each of the env deletion clones demonstrated that the virus particles were noninfectious.

Animals↗

tat regulates binding of the human immunodeficiency virus trans-activating region RNA loop-binding protein TRP-185.

The TAR element extending from -17 to +80 in the human immunodeficiency virus long terminal repeat (HIV LTR) is required for activation of gene expression by the tat trans-activator protein. TAR RNA forms a stable stem-loop structure, and mutagenesis studies indicate that the stem structure, the primary sequence of the loop, and the bulge element are the major determinants for tat activation. RNA gel retardation analysis demonstrates that both tat and cellular proteins bind to TAR RNA, but the mechanism by which these proteins increase HIV gene expression is unknown. We have fractionated HeLa cell nuclear extracts in an attempt to identify cellular proteins that bind to TAR RNA and are involved in regulating HIV gene expression. RNA gel retardation and UV cross-linking reveal that a cellular protein of 185 kD, which we designate TAR RNA-binding protein 185 (TRP-185), binds with both high affinity and marked specificity to TAR RNA. RNA gel retardation and competition analyses indicate that TRP-185 binding is strongly dependent on the TAR RNA loop sequences. The binding of TRP-185 is modulated by both a set of cellular cofactors and the tat protein. Highly purified preparations of TRP-185 are capable of activating in vitro transcription of wild-type, but not mutated, HIV LTR chloramphenicol acetyltransferase (CAT) constructs. These results characterize a positively acting cellular RNA-binding factor, TRP-185, which is involved in the regulation of HIV gene expression.

Amino Acid Sequence↗

Determination of IgE antibodies to Polistes dominulus, Vespula germanica and Vespa crabro in sera of patients allergic to vespids.

The study was undertaken to investigate the presence of IgE antibodies to Polistes dominulus (PD), Vespula germanica (VG) and Vespa crabro (VC) in a large group of sera belonging to patients sensitized to Vespids in Spain. RAST values showed that although the majority of patients had IgE antibodies to PD, VG and VC, there was a marked predominance of PD. These results were related to the distribution of the insect in the areas where the sera were obtained. Due to geographical and insect distribution differences, the whole area was divided into three zones: Central, East and South. Comparison of the positive RAST values obtained indicated that, although the positivity to PD predominated over VG and this over VC, there were significant differences in percentage positivities to each vespid in the different regions studied. The results of the RAST absorption studies indicated that in most instances patients were originally sensitized to one vespid and were RAST positive to the other venoms due to cross-reactivity. Only in a minority of cases were coexisting antibodies to two insects present. These results show that PD and VG are the important vespids followed to a lesser extent by VC. This study provides relevant information concerning insect distribution sensitivity in a European country.

Animals↗

Delayed allergic reactions to beta-lactams. Four cases with intolerance to amoxicillin or ampicillin and good tolerance to penicillin G and V.

We present four cases of delayed allergic skin reactions to amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin. The clinical symptoms reported by the patients, the intradermal skin tests and the controlled challenge results suggested that the mechanism was cellular mediated. In two patients these findings were supported by histopathological studies. Although delayed-type hypersensitivity reactions to beta-lactams with positive skin test seem rare, they can occur to penicillins in allergic patients. The production of these reactions by amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin emphasizes the role of the side chain in inducing allergic reactions to beta-lactams.

Adult↗

Delivery in an obstetric birth chair: a randomized controlled trial.

OBJECTIVE: To determine whether nulliparae whose second stage of labour is conducted in an obstetric birth chair have a lower incidence of instrumental delivery than those using a conventional delivery bed. DESIGN: Randomized controlled trial using sealed, opaque envelopes for allocation. SETTING: Delivery ward in a busy teaching hospital. PATIENTS: 1250 nulliparae with a singleton live fetus with cephalic presentation, without epidural anaesthesia, who had achieved full dilatation. INTERVENTION: Intention to conduct second and third stages of labour in either the Birth-EZ chair or the conventional delivery bed, as randomly allocated. MAIN OUTCOME MEASURES: Primary measure: vaginal operative delivery; principal secondary measures: duration of second stage, perineal trauma, blood loss, women's views, and neonatal status. RESULTS: Delivery in the birth chair did not result in a reduction in operative delivery, overall. However, there was a reduction in vaginal operative delivery for fetal heart rate abnormality. There was no beneficial effect on perineal trauma or puerperal perineal pain. Post-partum haemorrhage was more frequent in the birth chair group. CONCLUSIONS: Delivery in the birth chair does not offer any obvious advantage to women over delivery on a bed.

Consumer Behavior↗