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J Buesa

Publications and source records attributed to J Buesa.

30 records · Page 2Linked to original sources

Experience with ifosfamide in the EORTC Soft Tissue and Bone Sarcoma Group.

The Soft Tissue and Bone Sarcoma Group of the European Organization on Research and Treatment of Cancer has conducted a number of studies of chemotherapy in advanced disease over the past 15 years. Following the discovery that the CYVADIC regimen (cyclophosphamide/vincristine/doxorubicin/dimethyl imidazole carboxamide) was less active than had been reported originally, the individual components of CYVADIC were studied. This showed that doxorubicin had considerable activity and that ifosfamide 5 g/m2 given over 24 hours was at least as active as cyclophosphamide. Subsequent studies have therefore centered on a combination of doxorubicin and ifosfamide. A large randomized trial showed no significant benefit of doxorubicin/ifosfamide over single-agent doxorubicin, but the doses of doxorubicin were different. More recently, using bone marrow growth factors, it has been possible to increase the doxorubicin dose to that given as a single agent and also maintain the ifosfamide dose. This is now being tested in a randomized trial to determine whether improved response rates and other indicators of outcome will be seen.

Antineoplastic Combined Chemotherapy Protocols↗

Transformation of the dermatophyte Trichophyton mentagrophytes to hygromycin B resistance.

A transformation system for the ringworm-producing dermatophyte Trichophyton mentagrophytes has been developed. The system employs the plasmid pHIS, which contains a bacterial hygromycin B phosphotransferase gene linked to Cochliobolus heterostrophus regulatory sequences (B. G. Turgeon, R. C. Garber, and O. C. Yoder, Mol. Cell. Biol. 7:3297-3305, 1987). This plasmid confers hygromycin B resistance to T. mentagrophytes. The DNA was stably integrated into the fungal genome, and the number and sites of integrations varied among transformants. Transformant clones were capable of infecting guinea pigs. This system opens the way for the molecular genetic analysis of the interaction of T. mentagrophytes with epithelial animal tissues.

Animals↗

Review of the clinical trials activity of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer.

Despite the low incidence of sarcomas, the Soft Tissue and Bone Sarcoma Group has established itself as one of the more active cooperative groups of the European Organization for Research and Treatment of Cancer. Performing over a 10 yr period three phase III protocols (total entry 750 patients), three randomized phase II studies (464 patients), a pilot combination study (185 patients), and 12 phase II studies (406 patients). The new randomized phase III protocol for advanced soft-tissue sarcoma will provide an interesting test of the validity of the current membership policy, which has not discouraged the participation of enthusiastic new members. For extremity sarcomas, improved surgical techniques have increased the number of patients retaining functional limbs but have maintained excellent rates of local control. However, systemic metastasis remains a significant problem and presents a challenge for future adjuvant studies.

Adult↗

Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group.

The objective of this randomized phase II/phase III study was to investigate the efficacy and toxicity of equimolar doses of adriamycin (ADM) and 4-epiadriamycin (EPI) in patients with locally advanced and/or metastatic soft tissue sarcoma. Doses of ADM and EPI were 75 mg/m2 given as an i.v. bolus injection every 3 weeks. Two hundred and ten patients were entered into the study by 18 institutions. Twenty-eight patients were ineligible and 15 were non-evaluable, leaving 167 evaluable patients. The two treatment groups were well balanced for sex, performance status, age, prior radiotherapy, extent and site of disease. Rates of response were similar, 25% in the ADM group compared to 18% in the EPI group (P = 0.33), and there were no significant differences between the ADM and EPI groups with respect to median duration of response (45 weeks vs. 77 weeks, P = 0.08), time to progression (15 weeks vs. 12 weeks, P = 0.945), and median survival (41 weeks vs. 48 weeks, P = 0.363). Myelotoxicity as shown by leucopenia was significantly more pronounced in the ADM treated patients (P = 0.002). Other toxicities such as alopecia and nausea/vomiting were also more severe in the ADM group (P = 0.02 and 0.06, respectively). In conclusion, the use of equimolar doses of ADM and EPI in advanced soft tissue sarcoma produced response rates which did not differ significantly and were only slightly in favour of ADM. However, this was achieved at the expense of higher toxicity.

Adolescent↗

Cyvadic in advanced soft tissue sarcoma: a randomized study comparing two schedules. A study of the EORTC Soft Tissue and Bone Sarcoma Group.

Two hundred forty-six adults with advanced progressive soft tissue sarcoma received combination chemotherapy with cyclophosphamide, vincristine, Adriamycin (doxorubicin), and DTIC. They were randomly allocated to receive the four drugs simultaneously every 4 weeks (S1: CYVADIC), or pairs of drugs (S2: ADIC-CYV) alternating at 4 weekly intervals. One hundred sixty-two patients completed 8 weeks of chemotherapy, and were considered to be evaluable for response. There were 18 complete remissions and 25 partial remissions, an overall response rate of 26%, with a highly significant difference between the two arms in favor of S1 (38% versus 14%, P = 0.001). There were no significant differences between S1 and S2 in terms of median duration of remissions (62 versus 39 weeks), and median survival of responders (85 versus 80 weeks) and of all evaluable patients (43 versus 45 weeks). Karnofsky index (KI) was the single most important prognostic factor. Patients with KI 90-100 showed a remission rate of 41% (56% on the S1 regimen) in contrast with 14% in those with KI 50-80. No patient with a KI of 50 responded to chemotherapy. The main toxicities were nausea, vomiting, anorexia, alopecia and myelosuppression, but did not differ significantly between the two regimens. Our findings suggest that stratification according to KI is essential for studies on chemotherapy for advanced soft tissue sarcomas in order to make a valuable comparison of treatment results.

Adolescent↗

[Systemic cryptococcosis and pneumocystosis in an HIV-positive patient].

Cryptococcosis is one of the most common opportunistic infections in AIDS patients. Neurological symptoms are the most frequent clinical presentation of this fungal infection, and pulmonary involvement is clinically much less evident. We report the case of a patient who was treated in the emergency room for acute respiratory failure but who did not survive. Microbiologic and histopathologic studies demonstrated simultaneous pulmonary infections with Cryptococcus neoformans and Pneumocystis carinii. We discuss this clinical presentation of cryptococcosis with no neurological manifestations, and the importance of concurrent infections by several opportunistic organisms that may go unrecognized.

AIDS-Related Opportunistic Infections↗

Evaluation of reverse transcription and polymerase chain reaction (RT/PCR) for the detection of rotaviruses: applications of the assay.

Our aim was to evaluate the reverse transcription and polymerase chain reaction (RT/PCR) technique for the detection of rotavirus shedding by infected children as a routine diagnostic procedure, in comparison to the enzyme-linked immunosorbent assay (ELISA), electron microscopy (EM) and polyacrylamide gel electrophoresis (PAGE) of rotavirus double-stranded RNA. Two-hundred and twenty stool specimens were collected from infants and young children with diarrhoea, and 10-20% faecal suspensions were made. Several methods of rotavirus dsRNA extraction were assayed. Electrophoretic analysis of viral RNA was carried out on 10% polyacrylamide gels followed by silver staining. RT/PCR was performed using oligonucleotide primers specific for both 3' and 5' ends of the rotavirus gene encoding VP7 which are highly conserved among group A rotaviruses. Following RNA extraction with phenol-chloroform and ethanol precipitation, RT/PCR could detect rotaviral RNA in only 11 of 25 samples known to contain rotaviruses by conventional methods. The purification of RNA extracts by CF11 cellulose and the application of the RNAID method were equally effective in extracting RNA and/or removing inhibitory substances from the faecal samples. RT/PCR led to the detection of 66 positive samples from 220 specimens tested (30%), whilst 64 specimens were positive by ELISA (29%), 59 (26.8%) by PAGE and 56 (25.4%) by EM. In our study, RT/PCR was 100 times more sensitive than the ELISA test in detecting rotaviruses serially diluted in a faecal suspension. Although RT/PCR is theoretically much more sensitive than ELISA, PAGE and EM for detection of rotaviruses, great care must be taken to remove inhibitory substances from the enzymatic reactions. We do not consider that RT/PCR should replace immunoassays with high sensitivity and specificity for rotavirus testing in faecal samples, although this technique has other applications, like the search for rotavirus in different clinical specimens (sera, cerebrospinal fluid, respiratory secretions, etc.) and in environmental samples, as well as the typing of viral strains using serotype-specific primers.

Child↗

Fine needle aspiration cytology of soft-tissue lesions.

The use of fine needle aspiration (FNA) cytology was reviewed in 117 cases of soft-tissue lesions: 23 non-neoplastic lesions, 34 benign mesenchymal tumors and 60 histologically proven soft-tissue sarcomas. The soft-tissue sarcoma aspirates were classified according to their cytomorphology into five groups of possible histologic diagnoses. Difficulties were experienced in the correct diagnoses. Difficulties were experienced in the correct assessment of aspirates from low-grade malignancies. On the other hand, in high-grade malignant sarcomas and in recurrent or metastatic soft-tissue sarcoma, FNA cytology was useful in both the initial diagnosis of a new lesion (22 patients) and in the confirmation or exclusion of a suspected treatment failure (38 patients with recurrence or metastases). In the latter, FNA cytology supported the clinical data and reduced the number of repeat open biopsies. However, the final diagnosis of soft-tissue sarcomas should be based upon the histologic study of tissue sections.

Biopsy, Needle↗

[Enzymatic activities of Campylobacter jejuni, C. coli, and C. lari].

Susceptibility to nalidixic acid has been considered for a long time as an important test in the identification of the different species of the genus Campylobacter. However, due to the increasing development of resistance new laboratory tests are needed to carry out an accurate identification to the species level in combination with other typing schemes. We have evaluated the enzymatic activity of 180 Campylobacter spp. strains isolated from clinical specimens performing the Api ZYM system (bioMérieux) in order to assay whether different enzymatic patterns could help to characterize these microorganisms. Thirteen of the 19 enzymatic activities detected by the system (lipase-C14, valine arylamidase, cystine arylamidase, trypsin, chymiotrypsin, alpha-galactosidase, beta-galactosidase, beta-glucuronidase, alpha-glucosidase, beta-glucosidase, N-acetyl-beta-glucosaminidase, alpha-manosidase and alpha-fucosidase) were negative for all the strains tested, whereas 3 enzymes (alkaline phosphatase, acid phosphatase and naphtol-A-S-BI-phosphohydrolase) were detected in 96.6% of the strains. Esterase-C1, esterase lipase-C8 and leucin arylamidase showed a variable reactivity depending on isolates. Enzymatic activity patterns clearly differentiate all the C. lari strains from other Campylobacter species. No significant differences were detected among the enzymatic activities of C. jejuni and C. coli strains. Our study suggests that the Api ZYM system is easy to perform and a valuable method to be applied in the characterization of the campylobacteria as a complement to other biotyping and serotyping schemes.

Anti-Infective Agents↗