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Biomedical subjects

J Casal

Publications and source records attributed to J Casal.

At least 19 recordsLinked to original sources

The Self Diagnosis Method. A new methodology to assess environmental management in sea ports.

A methodology has been designed to assess the performance of the environmental management in sea ports. The Self Diagnosis Method, developed by two research teams and about sixty sea ports, allows the comparison of the current environmental situation with that corresponding to previous years and the assessment of the opportunities for improvement. The main objective is to review the management activities and procedures that affect the environment and the way the port authority handles significant environmental aspects. It has been designed as a "first level" tool: it can be applied in approximately six hours by a non-expert user. It is based on the ISO 14001 vocabulary, requirements and structure, and it can be considered as a first step in the voluntary implementation of an environmental management system for port communities.

Commerce↗

The use of different vaccination schedules for sows to protect piglets against Aujeszky's disease.

Several Aujeszky's disease virus (ADV) vaccination protocols of sows were evaluated with regard to the passive protection conferred on piglets in a recently built commercial farm. Three different groups of sows were vaccinated using a Bartha K-61 strain. One group received an inactivated vaccine during pregnancy and the other two groups received attenuated vaccines, either during pregnancy (day 65) or on the seventh day of lactation. At farrowing, sows vaccinated during lactation had lower seroneutralization titres than those vaccinated during pregnancy either with inactivated or attenuated vaccines. Accordingly, their piglets were the ones with lower levels of maternally transferred neutralizing antibodies. At 4 weeks of age, five piglets born of each group of sows were challenged intranasally with a neurotropic strain of ADV. Piglets born of sows vaccinated during pregnancy with inactivated and attenuated vaccines gained 1.50 kg bodyweight and 2.50 kg bodyweight during 7 days, respectively, and did not show clinical signs, while piglets from sows vaccinated during the previous lactation lost 0.60 kg and presented moderate to severe clinical signs of ADV. Vaccination of sows during pregnancy provided more protection against ADV for piglets than sow vaccination before mating. Piglets born from sows vaccinated with attenuated or inactivated vaccines did not present remarkable differences on protection.

Animals↗

Effects of amoxicillin subinhibitory concentrations on the cross-protection developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin-resistant serotype 6B Streptococcus pneumoniae strain.

A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration [C(max)]: 6.1 microg/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself). Mortality in nonimmunized animals treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100%. Antibiotic treatment in immunized animals produced mortality rates </=20% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents [no differences versus placebo] while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio of <1 and thus a null value for the time that serum levels exceed the MIC). This in vivo synergism offers a potential therapeutic strategy against resistant strains.

Amoxicillin↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗