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Biomedical subjects

J Roca

Publications and source records attributed to J Roca.

At least 181 records · Page 10Linked to original sources
PubMed1996

Pharmacological properties of quinoxaline derivatives as a new class of 5-HT3 receptor antagonists.

The pharmacological profile of five quinoxaline derivatives, a new class of 5HT3 receptor antagonists, is reported in the present study. All of the new compounds antagonized the effect of the selective 5-HT3 receptor agonist 2-methyl-5-HT in the isolated longitudinal muscle-myenteric plexus preparation (LMMP) of guinea-pig ileum. One of them, VC-605) was approximately three orders of magnitude more potent than ondansetron. In binding studies to 5-HT3 receptors from rat cerebral cortex membranes only VC-605 showed an affinity comparable to ondansetron. In the isolated rat oesophageal tunica muscularis mucosae preparation the new compounds, like 2-methyl-5-HT, only produced relaxation of the contraction induced by carbachol at high concentrations. In vivo, the quinoxaline derivatives were weak antagonists of the bradycardia response to 5-HT in the anesthetized rat. The quinoxaline derivatives, in particular VC-501 and VC-603, prevented retches and vomiting induced by 2-methyl-5-HT and cis-platinum in the ferret. The new compounds also enhanced the gastric emptying of solids in rats. The results obtained are probably indicative of the suggested species- and tissue-dependent differences in 5-HT3 receptor subtypes. The high potency and selectivity of one of the new quinoxaline derivatives, VC-605, at 5-HT3 receptors of guinea-pig ileum is remarkable. VC-605 may be a useful tool for further characterizing this possible 5-HT3 receptor subtype.

Animals↗
PubMed1996

Update '96 on pulmonary gas exchange pathophysiology in pneumonia.

The major determinant of abnormal pulmonary gas exchange in patients with pneumonia is characterized by marked increases in intrapulmonary shunt combined with mild to moderate ventilation-perfusion (VA/Q) inequalities. Other mechanisms influencing the levels of arterial hypoxemia, such as disequilibrium of alveolar to endcapillary oxygen diffusion or increased intrapulmonary parenchymal oxygen uptake, are trivial in the clinical arena. These pathophysiological findings mostly concur with the structural derangement of pneumonic areas. On breathing oxygen, the dispersion of pulmonary blood flow, an index sensitive to both normal and low VA/Q ratios, increases (worsens), suggesting that hypoxic pulmonary vasoconstriction is abolished, whereas intrapulmonary shunt remains unchanged. This response differs from that developed by patients with acute respiratory distress syndrome (ARDS) in whom shunt increases moderately, thereby suggesting the development of reabsorption atelectasis, but VA/Q abnormalities remain unaltered. The effects of different drugs aimed at blocking the cyclooxygenase pathway to potentially enhance the mitigated hypoxic pulmonary vasoconstriction in the consolidated lung regions have shown to be individually variable and, in general, minimally beneficial; in contrast, the recent introduction of aerosolized vasodilators may benefit patients.

Humans↗
PubMed1995

Prospective study of drug-resistant tuberculosis in a Spanish urban population including patients at risk for HIV infection.

From January 1988 to October 1992, the primary resistance to first-line antituberculous drugs in 501 tuberculous patients was evaluated prospectively. Three-hundred and seventeen patients were HIV-negative and 184 were HIV-positive; these patients had several different clinical forms of tuberculosis. Moreover, the acquired resistance to antituberculous drugs was studied in 295 non-AIDS patients and in 42 AIDS patients with evidence of antecedent tuberculosis treatment. The data indicated that during these five years there was no consistent and clear-cut trend toward greater frequency of primary drug resistance to any of the first-line antituberculous drugs. Primary drug resistance in HIV-positive patients (7.1%) did not differ significantly (p > 0.05) from that found in HIV-negative patients (8.2%). Among HIV-positive patients, the acquired drug resistance pattern was similar to that detected in HIV-negative patients although the frequency of resistance in the former (69%) was significantly higher (p < 0.01). During the study, resistance to isoniazid was almost constant in the acquired-resistance cases and was frequently associated with resistance to other drugs. Furthermore, the acquired resistance to isoniazid was often of a higher level (1 to 10 mg/l) than the primary resistance (0.2 mg/l), and those strains were usually catalase and peroxidase negative.

AIDS-Related Opportunistic Infections↗
PubMed1995

The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models.

VA21B7 (3-[2-(4'-piperonylpiperazinyl) indolyl] carboxaldehyde) was synthesized as a potential 5-HT3 receptor antagonist. Even though VA21B7 showed a higher affinity towards 5-HT3 receptors as compared to other receptors studied, it was not a potent 5-HT3 receptor antagonist either in the periphery or in the brain. In a simple animal model of anxiety such as the two-compartment box in mice, a remarkable anxiolytic-like effect was found at doses of 2-500 micrograms/kg IP and also at low oral doses, in the microgram range. These drug doses did not produce any significant effect on spontaneous motor activity of mice. The anxiolytic profile of VA21B7 was further explored using other models of anxiety in rats such as the elevated plus-maze and punished-drinking. VA21B7 was compared with standard 5-HT3 receptor antagonists such as ondansetron, tropisetron and granisetron, with the 5-HT1A agent buspirone and with diazepam. In the plus-maze, VA21B7 showed an anxiolytic-like profile after doses of 0.25-0.5 mg/kg IP or 2-4 mg/kg PO which did not modify the number of total entries into the open and closed arms of the maze. Diazepam, granisetron and tropisetron were also effective in this test but not ondansetron and buspirone. VA21B7 was also able to release suppressed behaviour in the punished-drinking test. The dose-response curve was bell-shaped with a peak at 2-4 mg/kg. At variance with other studies, 5-HT3 receptor antagonists also increased the number of shocks taken in this test and the dose-response curve was also bell-shaped. VA21B7 was not anticonvulsant like diazepam, its anxiolytic action in the light/dark test was not flumazenil-sensitive and there was no rebound anxiogenic effect on withdrawal from chronic VA21B7 treatment for 15 consecutive days. Moreover, VA21B7 was not amnesic like the benzodiazepines but low doses of 2-4 mg/kg reduced the memory deficits induced in rats by scopolamine. Much higher doses were necessary to decrease spontaneous motor activity in rats. Since VA21B7 appears to be well tolerated in rodents at high doses, we think that it is of potential interest as an anxiolytic in humans.

Analgesics↗
PubMed1995

Epidermal dysplasia and neoplasia in kidney transplant recipients.

BACKGROUND: Established data confirm an increased incidence of skin cancer, mainly squamous cell carcinoma (SCC), in long-term kidney transplant recipients (KTRs). OBJECTIVE: Our purpose was to investigate prospectively the type and frequency of neoplastic and preneoplastic skin lesions in KTRs during the first 3 years of immunosuppression, as well as the influence of potential risk factors. METHODS: Eighty-one consecutive KTRs were examined every 6 months during the first 3 years after transplantation. All survival analyses were performed with the EGRET statistical software package. RESULTS: After a median follow-up of 34 months, 25 skin cancers developed in 12 patients; the basal cell carcinoma (BCC)/SCC ratio was 3.1:1. The cumulative risk of skin cancer developing after 3 years of graft survival was 18.1%. Only age at the time of transplantation (p = 0.005) and occupational sun exposure (p = 0.048) had statistical significance as risk factors. CONCLUSION: In carefully supervised KTRs, a high incidence of cutaneous malignancy, mainly BCC, exists in the early posttransplant period. Sun exposure and the patient's age at the time of transplantation seem to be the most important risk factors.

Adult↗
PubMed1995

Relationship between serum IgE and airway responsiveness in adults with asthma.

BACKGROUND: General population studies have shown a relationship between total serum IgE levels and airway responsiveness, but this association has not been documented in patients with asthma. OBJECTIVE: The study assesses the cross-sectional relationship between IgE levels and airway responsiveness in 208 subjects who had had emergency department treatment for asthma at least 2 years earlier. METHODS: All participants completed a standardized respiratory questionnaire and underwent spirometry, allergy skin testing, and a dose-response methacholine challenge test. RESULTS: After adjusting for age and gender, the percentage of patients with asthma and airway responsiveness (provocative concentration causing a 20% fall in forced expiratory volume in 1 second [PC20] < or = 8 mg/ml) increased from 52% in the lower quintile of IgE to 72% in the upper quintile (p < 0.01). After adjusting for age, gender, baseline percent predicted forced expiratory volume in 1 second, and smoking, the association between IgE (both in quintiles and continuous) and PC20 appeared consistent and statistically significant (p < 0.01). This association was stronger in patients who were not given inhaled steroid (odds ratio for twice the concentration of IgE, 1.42; 95% confidence interval, 1.09 and 1.84), than in patients treated with inhaled steroid (odds ratio, 1.10; 95% confidence interval, 0.82 and 1.50). Eosinophilia and skin reactivity were associated with PC20 although to a lesser extent. CONCLUSION: These findings strengthen the role played by IgE in facilitating the development of bronchial responsiveness in patients with asthma.

Administration, Inhalation↗
PubMed1995

The mechanisms of DNA topoisomerases.

Recent structural and mechanistic studies, as well as the discovery of new enzymes in the DNA topoisomerase family, allow these enzymes to be classified into three groups. Each group reflects the evolution of three different mechanistic strategies to manipulate DNA topology.

Animals↗
PubMed1995

Motility, acrosome integrity and fertility of frozen ram spermatozoa treated with caffeine, pentoxifylline, cAMP, 2-deoxyadenosine and kallikrein.

The motility, acrosome integrity and fertility of ram spermatozoa were examined after treatment with five compounds (caffeine, pentoxifylline, cAMP, 2-deoxyadenosine and kallikrein). Semen was extended with a Tris-based medium and frozen in pellet form. The compounds were added at various concentrations to the semen before freezing or after thawing. Motility and acrosome characteristics were assessed over a 6-h post-thaw period of incubation at 37 degrees C. Of the five compounds examined, only pentoxifylline, when added after thawing, stimulated motility but had not effect on the acrosome integrity of spermatozoa. Pregnancy rates for ewes inseminated in the uterus with semen treated after thawing with Dulbecco's phosphate-buffered saline (PBS, control) or PBS containing pentoxifylline (15 mM in the thawed semen), were 16/39 (41%) and 22/42 (52%) respectively. Motility characteristics of spermatozoa assessed by image analysis (Hamilton-Thorne analyser) were initially better after treatment of thawed semen with pentoxifylline than with PBS ("percent motility', "percent progressive motility', "percent rapid', "percent moderate' and "percent static', P < 0.01 or P < 0.001), but there was a greater deterioration in these characteristics during post-thaw incubation in semen treated with pentoxifylline than in the controls. The deterioration in motility characteristics occurred within 4 h of thawing and this may have been responsible for the modest improvement in fertility of spermatozoa treated with pentoxifylline.

Acrosome↗
PubMed1995

Opiates or cocaine: mortality from acute reactions in six major Spanish cities. State Information System on Drug Abuse (SEIT) Working Group.

STUDY OBJECTIVE: To describe temporal and geographical variations in mortality from acute reactions to opiates or cocaine and the demographic and toxicological characteristics of persons who died from these in major Spanish cities between 1983 and 1991. DESIGN: Descriptive study. Data were obtained retrospectively from pathologists' reports. SETTING: Cities of Madrid, Barcelona, Valencia, Seville, Zaragoza, and Bilbao. SUBJECTS: Deaths from acute reactions to opiates or cocaine were defined as those in which pathologists' reports did not indicate any other cause of death and in which evidence was found of recent consumption of these drugs. MAIN RESULTS: The mortality rate from acute reactions to opiate/cocaine per 100,000 population in the six cities as a whole rose from 1.2 in 1983 to 8.2 in 1991. Average annual rates for the whole period ranged from 1.7 in Seville to 4.9 in Barcelona. The male/female rates ratio was 5.9:1. The mean age of persons who died rose from 25.1 years in 1983 to 28 years in 1991. In more than 90% of the cases in whom toxicological tests were undertaken opiates were detected, and the proportion in which benzodiazepines or cocaine were detected increased during the period studied. CONCLUSIONS: Between 1983 and 1991 mortality from acute reactions to opiates/cocaine rose dramatically in major Spanish cities and significant differences in mortality between cities were found. Deaths were concentrated among men and young people. Acute drug reactions became one of the leading causes of death in persons 15-39 years of age, representing 11.1% of mortality from all causes in 1988 for this age group. Future studies should examine the relationship between the temporal and geographical variations in this type of mortality and various personal, environmental and social factors.

Adolescent↗
PubMed1995

Salbutamol inhibits pulmonary effects of platelet activating factor in man.

Inhaled platelet-activating factor (PAF) provokes considerable pulmonary gas exchange disturbances in normal man and in patients with mild asthma, similar to those observed in acute severe asthma. To further examine the mechanisms involved in PAF-induced ventilation-perfusion (VA/Q) mismatch, eight healthy, non-atopic, nonsmoking subjects were studied after administration of PAF aerosol (24 micrograms). They had been previously treated with inhaled salbutamol (300 micrograms) in a randomized, double-blind, cross-over, placebo-controlled design. After placebo, PAF provoked a fall in total arterial white cell count with a rebound leukocytosis. As shown in a previous study, an overall index of VA/Q inequality (DISP R-E*, 1.64 +/- 0.10) showed a threefold increase (P < 0.006) that accounted for the increase (79%) in AaPO2 (p < 0.04) after PAF, while the respiratory system resistance (Rrs) rose by 16% (p < 0.02). In contrast, after pretreatment with salbutamol inhaled PAF had no effects on pulmonary gas exchange, Rrs, or white cell count; facial flushing and cough were also hindered. The results are consistent with the hypothesis that salbutamol inhibits PAF-induced venoconstriction in both the airway and pulmonary microcirculation.

Administration, Inhalation↗
PubMed1995

Gas exchange response to intravenous aminophylline in patients with a severe exacerbation of asthma.

In patients with acute exacerbations of asthma, the intravenous administration of bronchodilators, such as salbutamol, entails the potential risk of worsening pulmonary gas exchange, despite an amelioration of airflow obstruction. The present study was designed to investigate the effect of intravenous aminophylline on pulmonary gas exchange in patients hospitalized with a severe exacerbation of asthma. We studied 12 patients (aged 41 +/- 13 yrs) admitted to the hospital because of an exacerbation of asthma. The study was of a randomized, double-blind, placebo-controlled design. Six patients were treated with intravenous aminophylline and six received placebo, in addition to standard treatment with inhaled salbutamol and intravenous corticosteroids. Forced spirometry, respiratory gas exchange, ventilation-perfusion relationships assessed with the multiple inert gas elimination technique, and systemic haemodynamics were measured at baseline and 60 min after treatment started. In the aminophylline-treated group, mean theophylline plasma levels increased to 15.2 +/- 3.6 micrograms.ml-1, forced expiratory volume (FEV1) increased by 17 +/- 12%, and forced vital capacity (FVC) by 16 +/- 10%. The mean changes in FEV1 and FVC in the aminophylline-treated group were significantly higher than in the placebo-treated group. Likewise, minute ventilation increased by 23 +/- 14% and arterial carbon dioxide tension (PaCO2) decreased by 0.4 +/- 0.3 kPa (3 +/- 2 mmHg) during aminophylline infusion. No significant changes in arterial oxygen tension (PaO2) or in ventilation-perfusion distributions were shown in aminophylline-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Geographic variation in HIV infection among injecting drug users with Barcelona.

In response to a high incidence of AIDS among injecting drug users in Barcelona, Spain, the city established a program in four geographically distinct centers for assistance and surveillance. The centers provided testing, counseling, and monitoring of infectious diseases. In 1991-92, HIV rates were 33% in the northwest center, 39% in the western center, 39% in the east, and 71% in the south. Differences between the rates in the southern center when compared with those in the other centers were very significant (P < or = .001). These data show geographic variation of HIV infection within one city and substantiate the need to provide expanded medical care in the drug misuse treatment setting.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Hepatitis C virus in plasmapheresis donors].

UNLABELLED: The high prevalence of the hepatitis C virus (HCV) infection among plasmapheresis donors has been reported in several countries and Cuba. We have studied the possible relationship between the laboratory results and the real infectious state of the anti-HCV positive individuals, as well as the possible routes of infection in this population. MATERIALS AND METHODS: Retrospective data were analyzed and a prospective monthly serologic (anti-HCV) and biochemical (alanine aminotransferase) follow-up was established to 61 regular plasmapheresis donors, negative to hepatitis B markers, of a unit, which showed a prevalence of 48.3% of infection among these donors. RESULTS AND CONCLUSION: A direct correlation between the presence of antibodies to HCV and liver injury was found. No significant connection was observed between age, sex, race or sensitizing material with the positivity to anti-HCV, but it was significant with the time in plasma donation. Our results denote the risk of transmission of the HCV infection in the plasmapheresis units, pointing out the importance of the nosocomial route of infection.

Adult↗
PubMed1995

Platelet count, antiplatelet therapy and pulmonary embolism--a prospective study in patients with hip surgery.

Pulmonary embolism (PE) is a serious complication following hip surgery. Trials of antiplatelet thromboprophylaxis indicated a substantial reduction in PE rate, and we prospectively studied the effect of a combination of low-dose heparin and two different antiplatelets. Furthermore, our experience in previous studies suggested that platelet count (PC) levels could be useful to reliably suspect PE at a very early stage, and we prospectively tried to confirm our previous findings. Ours is a prospective study in 459 consecutive patients operated on because of hip fracture (265) or elective hip replacement (194), aimed to determine: 1) whether the benefits of antiplatelets plus heparin on PE outweigh the risks; 2) to assess the clinical usefulness of PC monitoring in these patients, so as to confirm whether PE could be recognized early. It was a prospective, randomized, double-blind study. All patients received unfractioned heparin (7500 IU sc twice daily, starting 2 h before operation). In addition, they received aspirin (200 mg thrice daily, with meals), Triflusal (300 mg thrice daily, with meals), or placebo. Real time B-mode ultrasonography (US) was performed on all patients on the 8-9th day after surgery. Venography was performed in patients with normal US, if clinical symptoms suggested venous thrombosis. Twelve out of the 459 patients (2.6%) had to discontinue prophylaxis, because of major bleeding (6 patients), or gastric intolerance (6 patients). There were no significant differences between groups in either deep vein thrombosis (26 patients (18%) with aspirin, 18 (12%) with Triflusal, 26 (17%) with placebo), or PE development (7 patients (5%) with aspirin, 3 (2%) with Triflusal, 8 (5%) taking placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

[The significance of cytomegalovirus infection in the period after a heart transplant].

Cytomegalovirus (CMV) infection is a frequent source of morbidity after heart transplantation. Risk factors for the development of CMV infection include the use of antilymphocyte preparations in the postoperative phase or as antirejection therapy, and seronegative patients who receive a heart from a seropositive donor. Clinical spectrum varies from a mild illness with low-grade fever and leukopenia, to a severe disease with organ manifestations. CMV interferes in the immune system, and may trigger cellular rejection episodes, having a possible role accelerating graft coronary vasculopathy. Thus, an aggressive and early diagnostic approach to the infection is mandatory. Quantitative monitoring of antibody titers, cultures and CMV antigenemia may be helpful in the clinical diagnosis. Cytomegalovirus prophylaxis strategies in high-risk patients remain controversial. Currently, ganciclovir is the most safe and effective agent for the treatment of CMV infection. A better knowledge of the pathogenic mechanism of CMV infection will probably help the development of new diagnosis technology and more effective prophylactic and treatment strategies.

Antigens, Viral↗