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Biomedical subjects

A Figueredo

Publications and source records attributed to A Figueredo.

10 recordsLinked to original sources

Physiological functions of hydroperoxidases in Rhodobacter capsulatus.

Rhodobacter capsulatus J1 has two hydroperoxidases: a catalase-peroxidase and a peroxidase. A mutant strain, AH18, that had no catalase-peroxidase was isolated. The growth rate under aerobic and photosynthetic conditions, respiration, superoxide dismutase and peroxidase activities, and pigment content of the mutant were similar to those of the wild type. AH18 was more susceptible to killing and to inhibition of nitrogenase by H2O2 but not by molecular oxygen. The incidences of spontaneous mutations were similar in both strains. Viable counts in aerobic but not anaerobic cultures of AH18 started to decline as soon as the cultures reached the stationary phase, and the rate of cell death was much higher in AH18 than in the wild type. It is inferred that the peroxidase provides protection against H2O2 in log-phase cells and that the catalase-peroxidase provides protection under the oxidative conditions that prevail in aging cultures. This protective function might be related to the dual activity of the latter as a catalase and a peroxidase or to its capacity to oxidize NADH, NADPH, and cytochrome c.

Acetylene

Polymerase chain reaction-based detection of Trypanosoma cruzi DNA in serum.

DNAs prepared from chagasic patients' sera were amplified by the polymerase chain reaction using oligonucleotide primers which anneal specifically to a highly repetitive sequence of Trypanosoma cruzi nuclear DNA. Samples from both acutely and chronically infected patients yielded positive results by this method. No significant difference was observed when either whole blood or serum samples of the patients were used. These results indicate that serum instead of whole-blood samples could be used for polymerase chain reaction-based detection of T. cruzi in field studies without the need of applying any special chemical treatment to the specimens. This would represent a considerable advantage due to the easier handling and transportation of serum as compared with whole-blood samples, especially in tropical climates.

Adolescent

[Coxsackie B4 and cytomegalovirus in patients with insulin-dependent diabetes].

The purpose of this work is to analyze the potential relationship between infection by Coxsackie and cytomegalovirus and the appearance of insulin-dependent diabetes (IDD). We have assessed complement fixing (CF) antibodies against both viruses in 22 samples of serum from other individuals, among which 11 were patients with a recent diagnosis of IDD--less than 3 months of evolution--(GP) and the remainder 11, supposed healthy individuals with similar age, sex and socioeconomic level (GC). In addition, the presence of anti-pancreatic islets antibodies (ICA) was assessed in 22 serum samples using the indirect immunofluorescence reaction. We have not observed any relationship between the presence of Coxsackie B or CMV antibodies and the appearance of IDD, since although the seroprevalence against CMV was higher in GP than in GC, such difference was not statistically significant. With respect to ICAs, they were only present in the GP samples as expected. Given the small size of the sample, this results are not conclusive and larger series need to be studied.

Adolescent

Addition of verapamil and tamoxifen to the initial chemotherapy of small cell lung cancer. A phase I/II study.

Based on experimental observations that verapamil and tamoxifen reverse multiple drug resistance, the authors investigated the feasibility of combining both agents with the initial chemotherapy of extensive small cell lung cancer. Overall, in a consecutive series of 58 patients the most important toxicity was myelosuppression, and there was a 24% rate of severe infections. Therapeutic results included 24% complete and 34% partial response rates, median time to disease progression of 32 weeks, and median survival of 46 weeks. In three consecutive cohorts of patients the dose of either tamoxifen or verapamil were escalated by 25% and 33%, respectively. The cohort of patients receiving verapamil 360 mg/day and tamoxifen 100 mg/day (level 2) had slightly more toxicity but also more responses than the other groups. Therefore, the authors recommend that these doses be used in controlled trials to confirm the promising results of their study.

Antineoplastic Combined Chemotherapy Protocols

Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.

Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.

Adult

Impaired production and lack of secretion of interleukin 1 by human breast milk macrophages.

Interleukin 1 (IL-1) production by human breast milk macrophages (HMMø) in response to bacterial lipopolysaccharides (LPS) was investigated in 49 healthy mothers and compared with that of blood monocytes (HMo). IL-1 activity in 24 h HMMø culture supernatants was in most cases below the assay detection limits and much smaller than that of stimulated HMo (72 +/- 17 u/ml). Intracellular IL-1 activity in response to LPS in HMMø raised from less than 2 +/- 1 u/ml to 19 +/- 12 u/ml and was similar to that found in stimulated HMo (16 +/- 4 u/ml). Neither the low IL-1 production by HMMø nor its release into supernatants could be increased by stimulating with higher LPS concentrations (40-400 micrograms/ml) or when longer culture times were assayed (24-72 h). Inhibiting the production of prostaglandins by adding indomethacin to HMMø cultures, caused no effect either on IL-1 production or on its secretion to supernatants. The presence of inhibitors for the IL-1 thymocyte proliferative assay, in supernatants from HMMø, was excluded by mixing experiments with a known amount of IL-1. Thus, we conclude that HMMø produce four or five times less IL-1 than HMo in response to LPS stimulus. Furthermore, HMMø are completely unable to release the IL-1 produced.

Adolescent

Mortality due to respiratory cancers in the coke oven plants of the Lorraine coalmining industry (Houillères du Bassin de Lorraine).

The main activity of the Houillères du Bassin de Lorraine (Lorraine Collieries), employing 23,000 operatives and executives, is coalmining. The coke production is carried out by two coke oven plants with a workforce of respectively 747 and 552 workers. The coal coking process entails the emission of noxious products such as polycyclic aromatic hydrocarbons (PAH) from the ovens. The influence of occupational exposure on mortality due to respiratory cancers, and particularly to lung and upper respiratory and alimentary tracts cancer, was investigated among a cohort of 534 male workers from the two coke oven plants who had retired from work between 1963 and 1982. The job history of each subject has been precisely reconstructed by indicating the duration of exposure on the ovens, close to the ovens, and in maintenance occupations. The cohort mortality has been analysed according to the method of indirect standardisation with reference to the French male population and by a case-control study concerning the consumption of tobacco per cohort. The mortality due to lung cancer is 2.51 times higher than expected. This excess of mortality differs, but not significantly, between the two coke oven plants (standardised mortality ratio equals 3.05 and 1.75 respectively). It is not significantly higher among subjects exposed for more than five years, directly exposed on the ovens or working near the ovens or at maintenance occupations on the ovens (SMR = 2.78), than among those exposed for less than five years (SMR = 2.35) or those not exposed at all. Even taking into account the excess of mortality due to lung cancers in the Moselle district (1.6 time that of France), the excess of lung cancers does not seem to be explained by the regional factor, or by tobacco and alcohol consumption. Although no significant relation was offered between lung cancer and the duration of exposure to PAH, even when taking smoking habits into account, the carcinogenic role of occupational nuisances cannot be excluded.

Age Factors

Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer.

Studies were analyzed to show the correlation of response with dose intensity of single-agent 5-fluorouracil (5-FU) against colorectal cancer, multiagent CMF (cyclophosphamide, methotrexate, 5-FU) regimens against advanced breast cancer, and adjuvant therapy in stage II breast cancer. In colorectal cancer studies, subgroups in which 5-FU was given by intravenous (IV) bolus, infusion, and orally were analyzed. One study reported delivered dose levels after reductions for toxicity. This allowed calculations of received dose intensity for the three dose levels, and comparison with projected dose intensities. The data suggest that the dose-intensity response line is steep, once a threshold dose intensity has been surpassed. An increase of only 100 mg/m2/wk of received dose intensity of 5-FU increased the response rate from 20% to 29%, which in relative terms was an increase of almost 50%. Received dose intensity may correlate with response, not only in groups of patients, but also in individual patients, and this may, in fact, be the most important application of the concept of dose intensity.

Antineoplastic Combined Chemotherapy Protocols

Metabolic changes during platelet storage.

Platelet concentrates (PC) were stored in plastic bags with continuous shaking at 4, 22, and 37 C. Various metabolic parameters were examined over a 72-hour period. At 22 C, the pH and PO2 declined over 72 hours while the PCO2 and lactate increased. Hypotonic shock declined to 70 per cent. This differed from the small amounts of CO2 and lactate found at 4 C and the marked accumulation of metabolites and almost complete loss of shock response at 37 C. Aggregation was always better maintained with 4 C storage. The toxic effect of the accumulation of metabolites on the platelets was tested by adding lactate to fresh PC at zero time. This was effective in lowering the initial pH, markedly inhibiting the response to aggregation and decreasing the total accumulation of lactate during storage, but did not produce an inhibition of hypotonic shock response. The effect of accumulation of toxic metabolites was further investigated by using 72-hour plasma and platelets and recombining each of them with fresh preparations. Platelets were tested under degassed conditions to outline the requirements for oxygen and gasious exchange. Surprisingly, there was less accumulation of lactate and CO2 and better hypotonic shock response. These experiments have detected various changes in viability markers in platelets that are stored under actual blood bank conditions and indicate that the accumulation of lactate is not totally responsible for the toxic inhibition of platelet performance that is found upon storage at 22 C.

Blood Cell Count