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Biomedical subjects

J Casal

Publications and source records attributed to J Casal.

At least 19 recordsLinked to original sources
PubMed2003

Gemcitabine, cisplatin and vinorelbine as induction chemotherapy followed by radical therapy in stage III non-small-cell lung cancer: a multicentre study of galician-lung-cancer-group.

PURPOSE: To determine the effectiveness of a gemcitabine-cisplatin-vinorelbine combination in patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (n=46) with stage III NSCLC and naive of therapy were recruited into the trial to receive gemcitabine (G, 1000 mg/m(2)) on days 1 and 8, cisplatin (C, 100 mg/m(2)) on day 1 and vinorelbine (V, 25 mg/m(2)) on days 1 and 8 every 21 days for three cycles. RESULTS: Two patients achieved complete response (CR) and 23 partial response (PR), overall response 52%. Subsequent radical surgery included nine patients of whom four were non-resectable and five were resected and with 1 CR. Radiotherapy was administered to 31 patients, and two achieved CR. The median time to progression and overall survival were 37 and 50 weeks, respectively. Grade 3-4 neutropenia and thrombocytopenia occurred in 35% of cycles, with two toxic deaths. Severe non-haematological toxicity was uncommon. CONCLUSIONS: This GCV combination is effective in patients with stage III NSCLC, and with an acceptable toxicity.

Adult↗
PubMed2002

Modification of bacteraemia by specific antibodies and relation with mortality in a pneumococcal mouse sepsis model.

The relationship between mortality and the bacteraemic profile was investigated in a pneumococcal (serotype 6B) sepsis BALB/c mouse model where animals received protection by specific hyperimmune serum. A single intraperitoneal dose of hyperimmune serum obtained from mice immunized with the heat-inactivated strain was administered (non-diluted or diluted to 1/4 or to 1/16) to 5-mice study groups 1 h prior to intraperitoneal inoculation with the infective inoculum (3.57 x 108 cfu/ml). Blood cultures were performed daily over 15 days, with 8 microl of blood being collected from the tail vein; the samples were resuspended in Todd-Hewitt broth containing 10% trisodium citrate and plated onto blood agar for colony counting. Animals included in the control group received placebo (PBS). Mortality was 100% in control animals within the first 48 h. Hyperimmune serum decreased and delayed mortality in a dose-related trend, producing 100%, 80%, 60% and 40% survival rates at 72, 96, 144 and 360 h, with non-diluted serum. Bacteraemic profiles with maximum colony counts > or =5 x 107 cfu/ml in blood during the follow-up period were related to > or =65% probability of death, regardless of the serum dilution administered.

Animals↗
PubMed2002

Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fc(gamma) RIIa polymorphism characteristics.

The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG(2)m and Fc(gamma)RIIa allotypes were determined. A history of drug abuse (P = 0.001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0.01), higher levels of HIV-1 viral load (P < 0.05), serum IgG (P < 0.01) and beta2-microglobulin (P < 0.01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG(2)m and Fc(gamma)RIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.

AIDS-Related Opportunistic Infections↗
PubMed2002

Beta-lactam modification of the bacteraemic profile and its relationship with mortality in a pneumococcal mouse sepsis model.

A sepsis BALB/c mice model was used to investigate the relationship between mortality and the bacteraemic profile produced by a serotype 6B Streptococcus pneumoniae clinical isolate (MIC/MBC of amoxicillin 4/4 mg/L and of cefotaxime 2/4 mg/L). Animals were treated subcutaneously with doses of amoxicillin or cefotaxime ranging from 6.25 to 50 mg/kg tds for 48 h, starting 1 h after intraperitoneal inoculation (2 x 10(7) cfu/mouse). Blood cultures were carried out daily over 15 days. A survival rate of 100% was obtained with amoxicillin 25 mg/kg and of 60% with cefotaxime 50 mg/kg. A statistically significant (P = 0.012) relationship was found between the maximum cfu/mL in blood and mortality. A maximum log cfu/mL of 6.5 was associated with an 84% probability of death.

Animals↗
PubMed2002

Beta-lactam activity against resistant pneumococcal strains is enhanced by the immune system.

Pandemic resistance in Streptococcus pneumoniae is compromising antibiotic activity. Antibiotics that act on the cell wall, such as beta-lactams, may have a combined effect with the immune system against S. pneumoniae, since both act on the bacterial envelope. This combined effect can be studied in vitro or in vivo with respect to bacterial killing, since lysis is the end-point of both beta-lactams and the immune system. We review here the in vitro increase in the bactericidal activity of aminopenicillins by non-specific immunity (complement and polymorphonuclear leucocytes). Few data are available on the collaboration of specific immunity and beta-lactams. We also review the effect of the presence of specific antibodies on the in vivo T > MIC needed for the therapeutic efficacy of amoxicillin, and on blood bacterial clearance in animal models. The effect that immunity has on pharmacodynamic parameters, such as T > MIC, in non-human studies may be used as a tool to predict the effect of these pharmacodynamic variations in overcoming resistance and its selection, in the context of increasing the use of pneumococcal conjugated vaccines.

Animals↗
PubMed2002

Antimicrobial susceptibility and pneumococcal serotypes.

The increase in antibiotic resistance and the possible changes in serotype prevalence as a consequence of a new conjugated vaccine have contributed to renewed interest in the study of pneumococcal serotypes and their antibiotic resistances. Spain still has one of the highest penicillin resistance rates, but in the past 4-5 years a slight decrease has been observed. The level of resistance has not increased either, 12.7% of the 11 165 isolates studied showed high-level penicillin resistance but 94% of these had an MIC of only 2 mg/L. Serotypes 6, 9, 14, 19 and 23 included 83% of the penicillin-resistant pneumococci; the remaining 17% belonged to 18 different serotypes. We analysed these minor penicillin-resistant serotypes in view of their potential increase following a possible child vaccination programme. Four of these serotypes (11, 15, 21 and 35) were the most prevalent, and among them serotype 15 was particularly frequent with >50% of its strains resistant. The effective control of these minor penicillin-resistant serotypes should be based on continuous surveillance of pneumococcal epidemiology.

Drug Resistance, Bacterial↗
PubMed2002

Effects of specific antibodies against Streptococcus pneumoniae on pharmacodynamic parameters of beta-lactams in a mouse sepsis model.

A dose-ranging study to investigate the in vivo effects of the presence of specific antibodies on the efficacy of beta-lactam treatment of sepsis caused by Streptococcus pneumoniae (non-beta-lactam-susceptible serotype 6B isolate) was performed with a BALB/c mouse model. Hyperimmune serum was obtained from mice immunized with the heat-inactivated strain. The rate of mortality was 100% in nontreated animals in the absence of specific antibodies. A single injection of a one-half or one-quarter dilution of hyperimmune serum produced 60 to 40% survival rates. In the absence of specific antibodies, the minimal effective doses of amoxicillin and cefotaxime that produced survival rates of 100 and 80% were 25 and 50 mg/kg of body weight (three times a day for up to six doses), respectively. These doses produced times that the levels in serum remained above the MIC (deltaT > MICs) approximately 30% of the dosing interval. When specific antibodies were present (by administration of a one-half or one-quarter dilution of hyperimmune serum), the minimal effective doses of the antibiotics were 3.12 and 6.25 mg/kg ( approximately 8 times lower), with the deltaT > MICs being approximately 3 and 5% of the dosing interval for amoxicillin and cefotaxime, respectively. This in vivo combined pharmacodynamic effect offers possibilities that can be used to address penicillin resistance.

Amoxicillin↗
PubMed2002

Pharmacoepidemiological analysis of provincial differences between consumption of macrolides and rates of erythromycin resistance among Streptococcus pyogenes isolates in Spain.

The M phenotype is by far the most common mechanism of erythromycin resistance among Streptococcus pyogenes isolates in Spain. A geographic analysis of the relationship between within-country differences in the prevalence of M-type resistance to erythromycin in S. pyogenes and the level of consumption of 14- and 15-membered macrolides within different provinces was carried out. From 1998 to 1999, a nationwide multicenter surveillance study yielded 2,039 consecutive pharyngeal isolates of S. pyogenes. Data on antibiotic consumption for the same period were gathered from IMS Health, and the corresponding daily defined doses per 1,000 inhabitants per day were calculated according to the Anatomic Therapeutic Classification index. Macrolide use was subdivided into dosages given three times a day (TID), twice a day (BID), or once a day (OD). Spearman nonparametric correlation coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were introduced into a linear regression model. The total consumption of macrolides presented a significant correlation with the prevalence of resistance (R = 0.527; P = 0.032). Neither TID nor BID macrolide consumption showed significant correlations. Only OD consumption had a significance below 0.1. These data are consistent with the hypothesis that only the total consumption of macrolides influences the local rates of M-type erythromycin resistance in S. pyogenes, and subgroups of macrolides seem to have an additive rather than a selective effect by contributing to increasing the final amount of macrolides used. Local variations in total consumption were associated only with BID consumption (R = 0.849; P = 0.004). The simple linear regression with total macrolide consumption showed a considerable determination coefficient (R(2) = 0.678; P = 0.006). The model explains up to 68% of the measured variation and is clearly better as a predictor of the prevalence of resistance than the mere mean is. By solving the regression equation, the resultant value of 2.2 defined doses per 1,000 inhabitants per day fits with the existence of a critical threshold of selective pressure.

Anti-Bacterial Agents↗
PubMed2001

Postmortem findings in captive cane rats (Thryonomys swinderianus) in Gabon.

The causes of morbidity and mortality in a population of cane rats (Thryonomys swinderianus) on an experimental farm in Gabon were monitored for 21 months; 94 of 546 animals (17.2 per cent) died and were examined postmortem, and complementary laboratory examinations were carried out on 23 of the cases together with samples from 13 other animals kept elsewhere in similar conditions. Twenty-six (28 per cent) of the deaths occurred in preweaned kits, 40 (42 per cent) in subadults and 28 (30 per cent) in adults. The average monthly mortality was 2.5 per cent. Trauma was responsible for 29 of the deaths, 12 were due to septicaemia, 10 to primary respiratory lesions, five to digestive disorders, four to urinary lesions, three to reproductive problems and three to other causes; no diagnosis could be reached in 28 cases.

Animals↗
PubMed2001

Identification of the psaA gene, coding for pneumococcal surface adhesin A, in viridans group streptococci other than Streptococcus pneumoniae.

The gene encoding the pneumococcal surface adhesin A (PsaA) protein has been identified in three different viridans group streptococcal species. Comparative studies of the psaA gene identified in different pneumococcal isolates by sequencing PCR products showed a high degree of conservation among these strains. PsaA is encoded by an open reading frame of 930 bp. The analysis of this fragment in Streptococcus mitis, Streptococcus oralis, and Streptococcus anginosus strains revealed a sequence identity of 95, 94, and 90%, respectively, to the corresponding open reading frame of the previously reported Streptococcus pneumoniae serotype 6B strain. Our results confirm that psaA is present and detectable in heterologous bacterial species. The possible implications of these results for the suitability and potential use of PsaA in the identification and diagnosis of pneumococcal diseases are discussed.

Adhesins, Bacterial↗
PubMed2000

Streptococcus pneumoniae resistance to erythromycin and penicillin in relation to macrolide and beta-lactam consumption in Spain (1979-1997).

Streptococcus pneumoniae resistance to penicillin and erythromycin in relation to beta-lactam and macrolide consumption in Spain over 19 years (1979-1997) was studied from resistance data collected by a search of the literature. Antibiotic consumption was expressed in defined daily dosage (DDD)/1000 inhabitants/day. A significant relationship (P: < 0.001) between erythromycin resistance (MIC >/= 1 mg/L) and global macrolide consumption (r = 0.942), as well as between high-level penicillin resistance (MIC >/= 2 mg/L) and global beta-lactam consumption (r = 0.948) was observed. The relationship between erythromycin resistance and macrolide consumption was due mainly to consumption of macrolides taken twice a day (adjusted r(2) = 0.886). Prevalence of high-level penicillin resistance correlated with consumption of oral cephalosporins (adjusted r(2) = 0.877); however, there appeared to be no correlation of consumption of oral or parenteral aminopenicillins, narrow-spectrum penicillins or cephalosporins with intermediate-level penicillin resistance (MIC 0. 12-1 mg/L). The prevalence of high-level penicillin and of erythromycin resistance were also strongly correlated with each other (r = 0.903, P: < 0.001). In addition to global consumption, different categories of resistance (high or intermediate), and the differential capability of antibiotics to select resistance, must be taken into account when studying antibiotic impact on bacterial populations. Although this ecological analysis is not able to demonstrate a causal relationship between antibiotic consumption and development of resistance, it suggests that overuse of certain specific antibiotics is more likely to be related to the increase in drug-resistant strains of S. pneumoniae.

Anti-Bacterial Agents↗
PubMed2000

Streptococcus pyogenes resistance to erythromycin in relation to macrolide consumption in Spain (1986-1997).

The relationship between Streptococcus pyogenes resistance to erythromycin and macrolide consumption in Spain was studied. Erythromycin resistance was highly correlated with the consumption of total macrolides (r = 0.88, P<0.01). When macrolides were grouped into posological subgroups according to their pharmacokinetic and pharmacodynamic properties and analysed separately, erythromycin resistance appeared to be related mainly to those macrolides taken twice daily (bd) (r = 0.86, P<0.01) and those taken once daily (od) (r = 0.87, P<0.01), but not to those taken four (qds) or three times a day (tds) (r = -0.04, P: = 0.90). A progressive increase in the erythromycin resistance curve was seen after the consecutive introduction of both bd and od macrolides, which contributed to the increase in the total macrolide consumption, replacing tds macrolide prescription. Although this ecological analysis cannot establish an unequivocal causal relationship between antibiotic consumption and S. pyogenes resistance, the data are consistent with the hypothesis that widespread use of macrolides, mainly of bd and od macrolides, resulted in an increased prevalence of S. pyogenes resistant to erythromycin in Spain.

Anti-Bacterial Agents↗
PubMed2000

Streptococcus pneumoniae in children in Spain: 1990-1999.

UNLABELLED: This study analyses the serogroups/types (SGTs) and resistance to penicillin and erythromycin of 3921 strains isolated from 1990 to 1999 in children aged 0-14 y in Spanish hospitals of all the autonomous communities. Based on the age of the children, strains have been divided into five groups: 0-6 mo, > 6-1 y, > 1-2 y, > 2-5 y and > 5 y. While only eight SGTs were responsible for 80% of the infections in children from 6 mo to 2 y of age, this number increased to 11 and 16 for the groups > 2-5 y and > 5-14 y, respectively. SGTs 6, 14 and 19 were prevalent in blood and otic exudates. SGTs 1, 4, 5, 12 and 18 were more frequent in invasive disease but serotype 3 was clearly associated with otitis. Serotypes I and 5 were quite significant in children of over 2 y of age, and this should be taken into account in future vaccine formulations. CONCLUSION: Although high, the rate of penicillin resistance in the paediatric population has remained stable in recent years. Conversely, erythromycin resistance is still increasing in our country. Coverage by the 7-valent vaccine was 78 and 81% for blood and otic isolates, respectively. These coverage levels would be increased by 9% and 3% if 9-valent (plus 1 + 5 serotypes) were used and by an additional 2.6% and 7.6% using the 11-valent (plus 3 + 7) formulation.

Adolescent↗