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Biomedical subjects

J Roca

Publications and source records attributed to J Roca.

At least 199 records · Page 11Linked to original sources
PubMed1994

[HIV infection declines among intravenous drug addicts in Barcelona: 1987-1993].

BACKGROUND: The evolution of the prevalence of HIV infection in intravenous drug addicts who initiate hospital detoxication was analyzed. METHODS: Six hundred fifty intravenous drug addicts (535 males, 115 females) were analyzed for HIV and surveyed in regard to demographic variables and the use of drugs over a period of 7 years (1987-1993): age, sex, year of initiation of intravenous drug addiction, length of the habit and year of admission. RESULTS: Most of the subjects were men (82%) with a mean age of 19.7 years at the time of initiation to the use of i.v. drugs and an age of 25.9 years on admission to the unit. The mean time of i.v. drug addiction at admission was 74 months. The characteristics of the patients according to the year of admission were homogeneous in regard to age, length of drug addiction and male/female ratio. More than 50% of the subjects had initiated the use of i.v. drugs during the first half of the last decade. The global prevalence of HIV infection was of 66.3% with no differences being observed between sexes. The frequency of infection was shown to have globally decreased from 1987 to 1993 (p = 0.06) although the rates of HIV infection in women did not significantly modify (p = 0.08) in contrast to that of men (p = 0.05). CONCLUSIONS: The epidemia of HIV infection in intravenous drug addicts may have entered into remission following a decade characterized by a spread in the use of heroin and great diffusion of the disease.

Adult↗
PubMed1994

DNA transport by a type II DNA topoisomerase: evidence in favor of a two-gate mechanism.

DNA substrates in which a supercoiled DNA is singly linked to a nicked or relaxed DNA ring were used to analyze the transport of one DNA ring through another by yeast DNA topoisomerase II. The enzyme binds preferentially to the supercoiled DNA and promotes decatenation efficiently upon binding of a nonhydrolyzable ATP analog. Analysis of the reaction products shows that the nicked or relaxed DNA ring released is not associated with the enzyme-supercoiled DNA complex. These results favor a two-gate model in which the DNA ring being transported can exit from the interior of the enzyme through a gate on the opposite side of the entrance gate, which is irreversibly closed upon binding of the nonhydrolyzable ATP analog.

Adenylyl Imidodiphosphate↗
PubMed1994

Synthesis of 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives with 5-HT3 antagonist and 5-HT4 agonist properties.

New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2e and 2f, were more potent than ondansetron in this regard. However, these two compounds were much weaker than the typical 5-HT3 receptor antagonist as displacers of [3H]BRL-43694 binding to rat cerebral cortex homogenates or as antagonists of the bradycardia response to 5-HT in the anaesthetized rat. Like the prokinetic agent cisapride, some of the new compounds enhanced gastric emptying in rats. Compound 2f not only markedly enhanced gastric emptying but was also a potent agonist at the isolated rat oesophageal tunica muscularis mucosae, a preparation sensitive to 5-HT4 receptor stimulation, and enhanced the twitch response in the LMMP preparation. The latter effect was blocked by a high concentration of tropisetron or by previous desensitization with 5-methoxytryptamine. Compound 2f appears to show a promising pharmacological profile as a potential gastrokinetic agent.

Animals↗
PubMed1994

Antitumor bisdioxopiperazines inhibit yeast DNA topoisomerase II by trapping the enzyme in the form of a closed protein clamp.

The mechanism of inhibition of eukaryotic DNA topoisomerase II [DNA topoisomerase (ATP-hydrolyzing), EC 5.99.1.3] by a member of the bisdioxopiperazine family of anticancer drugs, ICRF-193, was investigated by using purified yeast DNA topoisomerase II. In the absence of ATP, ICRF-193 has little effect on the binding of the enzyme to various forms of DNA. In the presence of ATP, the drug converts the enzyme to a form incapable of binding circular DNA. Incubation of a preformed circular DNA-enzyme complex with ICRF-193 and ATP converts the complex to a form stable in molar concentrations of salt. These results can be interpreted in terms of the ATP-modulated protein-clamp model of type II DNA topoisomerases [Roca, J. & Wang, J. C. (1992) Cell 71, 833-840]; ICRF-193 can bind to the closed-clamp form of the enzyme and prevents its conversion to the open-clamp form. This interpretation is further supported by the finding that whereas both ATP and the drug are needed to form the salt-stable circular DNA-enzyme complex, ATP is not needed for maintaining this complex; furthermore, a signature of the closed-clamp form of the enzyme, Staphylococcus aureus strain V8 endoproteinase cleavage site at Glu-680, is observed if the enzyme is incubated with both ATP and ICRF-193. Inhibition of interconversion between the open- and closed-clamp forms of type II DNA topoisomerases offers a new mechanism in the selection and design of therapeutics targeting this class of enzymes.

Adenosine Triphosphate↗
PubMed1994

Tuberculosis of the neural arch. A report of four cases.

Four cases of spinal tuberculosis involving the posterior neural elements are reported; all the patients were from Africa. The condition is rare and its incidence may be different in different races. Neural arch involvement is likely to be associated with neurological complications.

Adult↗
PubMed1994

Contribution of multiple inert gas elimination technique to pulmonary medicine. 1. Principles and information content of the multiple inert gas elimination technique.

This introductory review summarises four different aspects of the multiple inert gas elimination technique (MIGET). Firstly, the historical background that facilitated, in the mid 1970s, the development of the MIGET as a tool to obtain more information about the entire spectrum of VA/Q distribution in the lung by measuring the exchange of six gases of different solubility in trace concentrations. Its principle is based on the observation that the retention (or excretion) of any gas is dependent on the solubility (lambda) of that gas and the VA/Q distribution. A second major aspect is the analysis of the information content and limitations of the technique. During the last 15 years a substantial amount of clinical research using the MIGET has been generated by several groups around the world. The technique has been shown to be adequate in understanding the mechanisms of hypoxaemia in different forms of pulmonary disease and the effects of therapeutic interventions, but also in separately determining the quantitative role of each extrapulmonary factor on systemic arterial PO2 when they change between two conditions of MIGET measurement. This information will be extensively reviewed in the forthcoming articles of this series. Next, the different modalities of the MIGET, practical considerations involved in the measurements and the guidelines for quality control have been indicated. Finally, a section has been devoted to the analysis of available data in healthy subjects under different conditions. The lack of systematic information on the VA/Q distributions of older healthy subjects is emphasised, since it will be required to fully understand the changes brought about by diseases that affect the older population.

Exercise Test↗
PubMed1994

Clinical and functional characteristics of patients two years after being affected by the soybean asthma epidemic in Barcelona.

BACKGROUND: Patients affected during the asthma outbreaks caused by soybean dust inhalation in Barcelona presented with sudden onset of severe asthma followed by the rapid relief of symptoms after treatment. Two years after the epidemics ended, a case-control study was conducted in which the clinical, functional, and immunological characteristics of these asthma patients (a randomised sample of asthmatic patients admitted as emergency cases on epidemic days, n = 213) were compared with those of a control group (a random sample of asthmatic patients admitted as emergency cases for attacks of asthma on non-epidemic days, n = 170). METHODS: The study included the administration of the ATS-DLD78 standardised respiratory questionnaire, the measurement of atopy, and performance of spirometric tests and a methacholine inhalation test. RESULTS: Patients with epidemic asthma reported fewer symptoms of asthma, had attended emergency departments less frequently during the previous year for acute attacks of asthma, were taking fewer inhaled corticosteroids at the time of the study, and attended medical follow up less frequently than did the patients with non-epidemic asthma. However, the cases and controls showed no differences in ventilatory capacity or reactivity to the methacholine bronchoprovocation test. CONCLUSIONS: Two years after the end of the soybean epidemics, people affected by epidemic asthma had a favourable prognosis. This finding contrasts with a higher risk of life threatening asthma and death during the epidemics. This paradox could be the result of a complex interaction between host and conditions of exposure.

Asthma↗
PubMed1994

Effect of sampling site on femoral venous blood gas values.

To examine whether the tip of the femoral vein catheter used for sampling femoral venous PO2 during cycling exercise is contaminated by skin or saphenous vein blood, we studied 6 healthy volunteers [21.7 +/- 0.7 (SD) yr] during three identical incremental exercise tests while breathing room air on the same day. Femoral venous blood was sampled simultaneously from two catheters inserted into the femoral vein but advanced in opposite directions (7 cm distally and 5 cm proximally). Blood sampling for measurements of PO2, PCO2, pH, hemoglobin concentration, and oxyhemoglobin saturation was done simultaneously from both catheters in duplicate at rest, at 60% of maximum workload (60% W), and at maximum symptom-limited exercise (100% W). Temperature was measured with a thermistor probe placed in the proximal catheter. At rest, distal PO2 was significantly lower than that measured proximally (24.9 +/- 4.3 vs 30.8 +/- 6.1 mmHg, respectively; P < 0.004), but no differences were found during exercise (60% W, 23.6 +/- 3.4 vs. 24.5 +/- 3.6 mmHg; 100% W, 26.0 +/- 3.6 vs. 25.5 +/- 2.8 mmHg, respectively). Comparison of blood temperatures between proximal and distal sites of sampling in two subjects showed negligible differences. Intrasubject coefficient of variation of distal femoral venous PO2 over the three bouts of exercise was 11.5% (2.9 mmHg) at rest, 5.9% (1.4 mmHg) at 60% W, and 5.6% (1.5 mmHg) at 100% W. Mean differences in distal PO2 between duplicate samples were 0.5 +/- 1.4 mmHg at rest, 0.1 +/- 0.8 mmHg at 60% W, and 0.6 +/- 0.9 mmHg at 100% W.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease.

Morphologic changes in pulmonary muscular arteries may modify the mechanisms that regulate the pulmonary vascular tone and contribute to maintaining an adequate ventilation-perfusion (VA/Q) matching in patients with chronic obstructive pulmonary disease (COPD). To analyze the relationships between the abnormalities of pulmonary muscular arteries and the degree of VA/Q inequality, and to assess the effect of these abnormalities on the changes in VA/Q relationships induced by oxygen breathing, we studied a group of patients with mild COPD undergoing resective lung surgery. According to the degree of airflow obstruction and the increase in VA/Q mismatch produced by 100% O2 breathing (delta logSD Q), patients were divided into three groups: (A) patients with normal lung function, (B) patients with airflow obstruction and a high response to oxygen (delta logSD Q > 0.4), and (C) patients with airflow obstruction and a low response to oxygen (delta logSD Q < 0.4). Pulmonary arteries in Groups B and C showed narrower lumens and thicker walls than in Group A. These morphologic changes were produced mainly by an enlargement of the intimal layer and were more pronounced in Group C than in Group B. The assessment of intimal area as a function of artery diameter showed that the increase in intima in Group C took place predominantly in arteries with small diameters (< 500 microns). The mean intimal area on each subject correlated with both the PaO2 value (r = -0.46, p < 0.05) and the overall index of VA/Q mismatching (r = 0.51, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

Effects of PEEP on VA/Q mismatching in ventilated patients with chronic airflow obstruction.

Recent work in patients with acute respiratory failure (ARF) due to exacerbation of chronic airflow obstruction (CAO) suggests that application of low degrees of positive end-expiratory pressure (PEEP) can improve rather than impair respiratory mechanics, because PEEP replaces intrinsic PEEP (PEEPi). However, the impact of PEEP on pulmonary gas exchange has not been fully investigated. We designed this study to examine the effects of PEEP and those of PEEPi on ventilation/perfusion (VA/Q) mismatching in mechanically ventilated patients with CAO. Eight patients were studied under four conditions: (1) during controlled mechanical ventilation with the ventilatory setting established by the attending physicians (PEEPi-100%), according to standard criteria; (2) after application of PEEP amounting to 50% (PEEP-50%), and then (3) to 100% (PEEP-100%) of the original PEEPi; and finally, (4) after reduction of PEEPi to 50% of the initial value (PEEPi-50%), obtained by increasing expiratory time and decreasing respiratory rate and tidal volume. Respiratory mechanics, hemodynamics, respiratory blood gases, and VA/Q distributions were measured during each ventilatory mode. At low values of PEEP (PEEP-50%) no changes in respiratory mechanics nor in hemodynamics were observed, but PaO2 moderately increased (from 103 +/- 25.2 to 112 +/- 29.6 mm Hg) and PaCO2 slightly decreased (from 42 +/- 3.7 to 40 +/- 3.3 mm Hg) essentially because of an increase in the mean VA/Q ratio (first moment) of both flood flow (Q, from 0.65 +/- 0.28 to 0.78 +/- 0.29) and ventilation (V, from 4.02 +/- 1.55 to 4.93 +/- 2.00) distributions (p < 0.05, each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Inhaled platelet-activating factor worsens gas exchange in mild asthma.

To investigate the potential effects of inhaled platelet-activating-factor (PAF) (12 micrograms) to perturb pulmonary gas exchange in bronchial asthma, six patients (mean +/- SE, 23 +/- 2 yr) with intermittent asthma (FEV1, 90% predicted) were studied before and 5, 15, and 45 min after challenge. Circulating white blood cells, respiratory system resistance (Rrs), systemic and pulmonary hemodynamics, and respiratory and inert pulmonary gas exchange were measured. Five minutes after PAF leukocytes fell, Rrs increased (by 27%). PaO2 decreased (by 15 mm Hg), and AaPO2 increased (twofold) (p < 0.05 each). Ventilation-perfusion (Va/Q) distributions worsened in a pattern similar to that commonly observed in patients with moderate to severe asthma. Dispersions of pulmonary blood flow (log SD Q) and of alveolar ventilation (log SD V), and an overall index of Va/Q heterogeneity (DISP R-E*) increased significantly (123% for DISP R-E*; p < 0.05, each). Gas exchange indices and Rrs were still minimally abnormal at 15 min but returned towards baseline at 45 min. Ventilatory and hemodynamic variables remained unaltered throughout the study. These results suggest that endogenous PAF may be implicated in the arterial blood gas abnormalities shown during exacerbations of bronchial asthma.

Administration, Inhalation↗
PubMed1994

Platelet-activating factor causes ventilation-perfusion mismatch in humans.

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Adolescent↗
PubMed1994

Clinical and functional assessment of patients with idiopathic pulmonary fibrosis: results of a 3 year follow-up.

The purpose of this study was to analyse the information provided by different techniques used in the assessment of patients with idiopathic pulmonary fibrosis (IPF) and their role in the prediction of lung function decline with the decline. Twenty seven subjects with IPF (55 +/- 14 (mean +/- SD) yrs) were studied at the initial staging. Nineteen of them (70%) were included in a follow-up over 3 yrs (32 +/- 6 months), whilst the remaining 8 patients were lost to follow-up. During the period of the study, 6 of the 19 patients died. A significant correlation between diffusing capacity of the lungs for carbon monoxide (DLCO) (and carbon monoxide transfer coefficient (KCO) = DLCO/alveolar volume (VA)) and the increase in alveolar-arterial oxygen tension difference (A-aPO2) during exercise (delta A-aPO2) was observed at diagnosis (r = -0.58). Despite the treatment with prednisone (1 mg.kg-1 daily during 4 weeks, tapered to an individualized maintenance daily dose of 15-30 mg), the 13 patients controlled throughout the whole period of the study showed a marked impairment in lung volumes; forced vital capacity (FVC) -0.46 +/- 0.09 l, from 69 +/- 16 to 52 +/- 11% of predicted, and total lung capacity (TLC) -0.39 +/- 0.11 l, from 75 +/- 16 to 62 +/- 14%, and in DLCO -0.6 +/- 0.2 mmol.min-1.kPa-1, from 56 +/- 15 to 47 +/- 18%, predicted. By contrast, both mean arterial oxygen tension (PaO2) and A-aPO2 at rest remained unchanged throughout the 3 yrs follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Arterial oxygenation does not predict the outcome of patients with acute respiratory failure needing mechanical ventilation.

One hundred and eighteen patients consecutively submitted to mechanical ventilation during a one year period, and admitted to the Respiratory Intensive Care Unit of the Hospital Clinic of Barcelona, were prospectively studied in order to define the importance of hypoxaemia as a predictor of mortality. Using a discriminant multivariate analysis, the following variables were selected as the best predictors of outcome: 1) the number of associated complications (NAC) on admission; 2) the simplified acute physiologic score (SAPS); 3) oxygenation index (PAO2-AaPO2)/PAO2 + 0.014 positive end-expiratory pressure (PEEP); and 4) the age of the patients. Using these predictors, 84% of the patients were accurately classified as survivors or as nonsurvivors. The partial contribution of each predictor to the model was also assessed using a logistic regression, by eliminating each single predictor and each possible pair of predictors. Using this means of analysis, the NAC and SAPS were the only predictors of mortality. The inclusion of short-term mechanically-ventilated patients did not bias the accuracy of prediction.

Aged↗