The effect of moisture regimes on the anaerobic degradation of municipal solid waste from Metepec (México).

The State of México, situated in central México, has a population of about 14 million, distributed in approximately 125 counties. Solid waste management represents a serious and ongoing pressure to local authorities. The final disposal site ("El Socavón") does not comply with minimum environmental requirements as no liners or leachate management infrastructure are available. Consequently, leachate composition or the effects of rain water input on municipal solid waste degradation are largely unknown. The aim of this work was to monitor the anaerobic degradation of municipal solid waste (MSW), simulating the water addition due to rainfall, under two different moisture content regimes (70% and 80% humidity). The study was carried out using bioreactors in both laboratory and pilot scales. The variation of organic matter and pH was followed in the solid matrix of the MSW. The leachate produced was used to estimate the field capacity of the MSW and to determine the pH, COD, BOD and heavy metals. Some leachate parameters were found to be within permitted limits, but further research is needed in order to analyze the leachate from lower layers of the disposal site ("El Socavón").

Deoxyuridine metabolism in cultured human lymphoblasts treated with methotrexate.

The deoxyuridine suppression test and labeled deoxyuridine incorporation studies assume a stable level of deoxyuridine phosphorylase (thymidine:orthophosphate deoxyribosyltransferase, EC 2.4.2.4) activity. We report a large increase in deoxyuridine phosphorylase activity in three of five cultured lymphoblast lines treated with 10(-7) M methotrexate. In two of these lines, a parallel increase in tritiated deoxyuridine incorporation into RNA was seen following methotrexate treatment. The high basal deoxyuridine phosphorylase activity in another lymphoblast line was associated with 80% incorporation of tritiated deoxyuridine into RNA in untreated cells. Since methotrexate-induced changes in deoxyuridine phosphorylase activity were time dependent, the reliability of the deoxyuridine suppression test and labeled deoxyuridine incorporation into DNA as measures of thymidylate synthetase (EC 2.7.4.6) inhibition would also vary with time. Moreover, increases in deoxyuridine phosphorylase activity in methotrexate-treated cells may influence the metabolism of fluorouracil, a drug frequently used in combined treatment regimens.

A randomized comparison of single-agent doxorubicin and epirubicin as first-line cytotoxic therapy in advanced breast cancer.

One hundred forty-one patients with advanced breast cancer who had not received prior chemotherapy were randomly assigned to receive doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks. These doses were selected to produce equivalent toxicities. All patients were assessed for toxicity, and 138 patients were assessable for response. After a median of five treatment cycles, 47% (32 of 68) of doxorubicin-treated patients achieved a partial or complete response. Response duration and survival were 10 and 12 months for doxorubicin and 8 and 10 months for epirubicin, respectively. Noncardiac toxicities were similar for both drugs. Of 41 patients receiving doxorubicin who had serial left ventricular ejection fraction assessments, seven sustained a fall of 10% or more, and one patient developed congestive cardiac failure at a cumulative doxorubicin dose of 489 mg/m2. Of 39 patients receiving epirubicin who had serial cardiac assessments, five sustained left ventricular ejection fraction falls of 10% or more and two patients developed congestive cardiac failure at cumulative doses of 178 mg/m2 and 833 mg/m2. These data indicate that an epirubicin dose of 90 mg/m2 produces toxicity equivalent to doxorubicin 60 mg/m2 but does not improve response rates, response duration, or survival in advanced breast cancer.

Mitomycin C, melphalan and methotrexate combination chemotherapy for palliation of disseminated breast cancer.

Fifty-seven patients with metastatic breast carcinoma have been treated with mitomycin C (10 mg/m2 IV 6-weekly), melphalan (6 mg/m2 PO X 3 days, 3-weekly), and methotrexate (35 mg/m2 IV 3-weekly) to assess the efficacy and toxicity of this regimen. Of 48 evaluable patients 19 (40%) responded for a median period of 5 months and 12 (25%) had stabilisation of disease. Of the 12 patients previously treated with adriamycin only one responded, whereas 18 of the 36 patients without previous chemotherapy responded. Although healing of bone metastases was infrequent control of hypercalcaemia was commonly seen. Generally the treatment was well tolerated and treatment was stopped in only five patients because of toxicity. Cumulative marrow toxicity was observed but was not a significant problem in the first 6 months of treatment. Mitomycin C, melphalan, and methotrexate (MMM) appears to provide an effective, well tolerated chemotherapy combination for metastatic breast carcinoma.

The modulating effects of flurbiprofen on adriamycin plus vincristine or vindesine in the treatment of advanced breast cancer.

To assess the modulating effects of a non-steroidal anti-inflammatory drug on chemotherapeutic agents, 183 patients with advanced breast cancer have been treated in a randomised study with flurbiprofen or placebo and adriamycin plus a vinca alkaloid. To assess the efficacy of the new vinca alkaloid, vindesine, in breast cancer, patients were further randomised to receive vindesine or vincristine. The overall response rate in evaluable patients was 57%, and the median duration of response in the different treatment groups varied from 6 to 10 months. Response rates and toxicity in vindesine- and vincristine-treated patients were similar, although with vindesine neurotoxicity was slightly lower. Flurbiprofen did not improve the response rate or reduce the toxicity of adriamycin plus vinca alkaloid.

Prostaglandin E1 inhibits acute cell dehydration thirst.

Intraperitoneally injected PGE1 (100 micrograms/Kg) inhibits specifically the drinking induced by both IP and IV 2 M NaCl (6 ml/Kg) and compound 48/80 (100 micrograms/Kg, IP). Probenecid (150 mg/Kg, IP) which is not a dipsogen, has no effect on the PGE1 induced inhibition of acute cell dehydration thirst. It is concluded the PGE1 acts upon the peripheral mast cells, inhibiting their secretion and thus affecting the water intake associated with the activation of these cells either by hypertonicity or specific stimulants of amine release. These results raise the possibility that endogenous prostaglandins might be involved in the modulation of some of the signals which convey to the brain information on the tonicity of the body fluids.

A strategy for improved results in ovarian carcinomas: partially responsive to chemotherapy.

Eighty-nine patients with FIGO stages 3 and 4 epithelial ovarian cancer who responded to cis-platinum alone or cis-platinum containing combinations have been studied retrospectively to determine the time taken to achieve maximum tumour response. Clinically determined partial and complete responses were seen within 2-6 (median 3) treatment courses and 2-5 (median 3) treatment courses respectively. Sixty-nine patients were restaged surgically demonstrating partial and complete response within 4-12 (median 5) and 3-16 (median 5) treatment courses respectively. After the initial 6 courses of chemotherapy, 53 patients showing a partial response continued with the same drugs but only 1 patient ultimately achieved a surgically confirmed complete response. Since second line drugs rarely achieve complete response following tumour progression we propose that patients who have only achieved partial response following 6 treatment courses should change chemotherapy in an attempt to achieve complete response.

Quality of life scales for patients with cancer: how often to administer?

AIMS: To determine the optimum frequency of quality of life assessment in patients with cancer. METHODS: The Spitzer unidimensional overall quality of life scale was administered to 41 patients with cancer comparing a monthly assessment with averaged weekly assessments (group 1) and two monthly assessment with averaged weekly assessments (group 2). RESULTS: Monthly and two monthly measures reflected the averaged weekly scores well although some patients reported difficulty recalling quality of life over the two month period. However patients generally preferred the weekly assessments. CONCLUSION: For longitudinal study of quality of life in patients with cancer weekly assessment is optimal. If weekly assessment is practically difficult monthly or two monthly measurements give a good reflection of averaged weekly scores but patients are more comfortable with monthly rather than two monthly measurements.

Sensitivity of Bidens laevis L. to mutagenic compounds. Use of chromosomal aberrations as biomarkers of genotoxicity.

The wetland macrophyte Bidens laevis possesses suitable cytological characteristics for genotoxicity testing. To test its sensitivity as compared to terrestrial plants species currently in use in standardized assays, Methyl Methanesulfonate (MMS), N-ethyl-N-nitrosourea (ENU) and Maleic Hydrazide (HM) were used. On the other hand, the insecticide Endosulfan (ES)--an environmentally relevant contaminant--was assayed in seeds and two-month old plants. Mitotic Index (MI), frequency of Chromosome Aberrations in Anaphase-Telophase (CAAT) and frequency of Abnormal Metaphases (AM) were analyzed. MH, MMS and ENU caused a significant decrease of the MI. MMS was aneugenic whereas MH and ENU were both aneugenic and clastogenic. ES caused a significant concentration-dependent increase of total- and aneugenic-CAAT in roots and a significant high frequency of AM at high concentrations. Because of its sensitivity to mutagenic substances, B. laevis can be regarded as a reliable and convenient species for genotoxicity assays especially if aquatic contaminants are evaluated.

The metabolic basis of deoxyuridine cytotoxicity. Studies of cultured human lymphoblasts.

The metabolic consequences of deoxyuridine treatment in four cultured human lymphoblast lines (CCRF-CEM, RPMI-8402, JM, and BALM) were studied by cell growth experiments, flow cytometry, and measurement of 2'-deoxyribonucleoside triphosphate (dNTP) levels. DNA perturbations occurred in all lymphoblast lines, but there was no significant impairment of RNA synthesis. The DNA perturbations in CCRF-CEM, RPMI-8402, and BALM cells reflected inhibition of DNA synthesis, and the associated dNTP changes were consistent with ribonucleotide reductase inhibition or, specifically in BALM cells, with DNA alpha-polymerase inhibition. JM cells treated with an intermediate concentration of deoxyuridine developed a block at the G1/S boundary which was deoxyuridine concentration-dependent, but not specific for deoxyuridine (it was also seen with thymidine treatment) and not related to DNA synthesis inhibition. There were no idiosyncratic dNTP effects accompanying the G1/S boundary block, and the responsible metabolic mechanism remains to be determined.

Assessment of antimetabolite cytotoxicity: a comparison of clonogenic assays and tritiated deoxyuridine incorporation.

A comparison has been made between the cloning capacity and changes in tritiated deoxyuridine (6-[3H]-UdR) incorporation of L1210 (murine leukaemia) and PMC-22 (human melanoma) cells treated with methotrexate (MTX), 5-fluorouracil (5-FU) and cytosine arabinoside (ARA-C). The labelling-cloning relationship was poor, with brief drug exposure times, but improved progressively after drug treatment of 1 cell-cycle time's duration. Labelling changes resulting from short-term exposure to drug (several hours) provided poor predictions of the cytotoxicity resulting from longer drug exposure.

A comparison of time trade-off and quality of life measures in patients with advanced cancer.

Quality of life (QOL) measures are now accepted as indicators of efficacy in the palliative treatment of cancer. Utility measures may also provide valuable information in this area yet they have rarely been applied. To assess the concordance of QOL and utility scales, 93 patients with advanced, symptomatic cancer completed two QOL instruments, the Spitzer Quality of Life Index (QLI) and Spitzer Uniscale, and a time-trade off (TTO) question reflecting the utility of their health states. The scales were self-administered. All patients completed the QLI and Uniscale but only 37% of participants were prepared to trade time. The remainder comprised 39% who felt too well to trade time and 24% who did not wish to consider trading time at all. Those prepared to trade time had significantly worse scores on both QLI and Uniscale instruments than those who felt too well to trade. However the correlation between time traded and QLI and Uniscale scores was poor. We conclude that the TTO question used in this study, while not strongly related to QOL, provides a measure of the patient's attitude to their health state. This may explain why patients differ in their attitude to quantity vs. quality of life.

A longitudinal study of health related quality of life and utility measures in patients with advanced breast cancer.

Health related quality of life (HRQOL) measures are now accepted as indicators of efficacy in the palliative treatment of cancer. Utility measures may also provide valuable information yet they have been applied less frequently. To assess the application of a time trade-off (TTO) utility measure and its concordance with the Spitzer uniscale and quality of life index (QLI) 38 women with advanced, symptomatic breast cancer were studied over a 12 month period. The correlation coefficient for QLI and TTO values was 0.54 and for uniscale and TTO 0.62. Using generalized estimating equations the regression of TTO scores on QLI and uniscale scores was significant at baseline. In longitudinal analyses results were significant only for QLI. Although all participants completed the HRQOL measures only 24 (63%) were prepared to trade time. The remaining 14 (32%) stated they felt too well to trade. Those prepared to trade time recorded significantly worse mean HRQOL scores throughout the study compared to those who felt too well to trade and had tumors which showed a poorer response to therapy. In this preliminary study utility and HRQOL scores were generally favorable throughout the 12 month study period and showed fair to moderate concordance. Further research in larger patient groups is required to better define the relationships between utility and HRQOL measures.

Detection of breast carcinoma metastases in bone: relative merits of X-rays and skeletal scintigraphy.

Of 1116 patients receiving primary treatment for breast carcinoma at the Royal Marsden Hospital since 1976, 651 had an abnormal bone scintigram either at primary diagnosis (378) or on subsequent follow-up (273) and 167 developed radiographically detectable bone metastases (21 at the time of primary diagnosis). Comparison of bone scintigrams and X-rays showed that scintigraphy was an inaccurate localiser of existing radiographic detectable metastases. If X-rays alone are used to detect bone metastases a limited examination with five plates will detect metastases with 92% accuracy. After primary surgery, routine X-ray screening for bone metastases is not necessary since it is possible to identify patients at risk on the basis of clinical examination, chest X-ray, and serum alkaline phosphatase and gamma-glutamyl transpeptidase levels.

Results of the surveillance policy of stage I non-seminomatous germ cell testicular tumours.

A series of 115 patients with clinical Stage I non-seminomatous germ cell testicular tumours were managed with orchiectomy and close surveillance (median follow-up 36 months, range 3-119); 34 (29.5%) relapsed, 21 within 6 months, 29 within a year and the latest at 28 months. At relapse all patients were treated with platinum or analogue-based drug combinations, supplemented in 7 by retroperitoneal node dissection; 30 patients achieved durable remissions and 2 have had further relapses successfully treated. Two died; both had malignant teratoma intermediate with primary stage T1 and vascular and/or lymphatic invasion of primary tumour. At a median follow-up time of 36 months, the survivors (98.3%) demonstrate no evidence of disease, these results matching the outcome of other methods of management. Vascular and/or lymphatic invasion was associated with an enhanced relapse rate but specific histology, T stage of the primary and pre-orchiectomy serum alpha-fetoprotein status did not appear to favour relapse. The first sign of relapse was tumour marker alone in 10 patients, radiological features alone in 12, or both in 10 patients. However, in 2 cases the relapse was first detected clinically. Furthermore, pre-orchiectomy and relapse marker status did not correlate well. These points emphasise the importance of all aspects of follow-up, none of which can be safely omitted.

Late results of surveillance of clinical stage I nonseminoma germ cell testicular tumours: 17 years' experience in a national study in New Zealand.

OBJECTIVE: To re-evaluate a national prospective study in New Zealand after 17 years to define whether orchidectomy alone and surveillance for nonseminoma germ cell testicular tumour (NSGCTT) is a sound policy and matches the results achieved by other treatment protocols. PATIENTS AND METHODS: Between 1980 and 1997, 248 men with stage I NSGCTT, from six New Zealand centres, were managed by orchidectomy alone and surveillance, with treatment of relapses using combination chemotherapy. RESULTS: Seventy of the 248 patients (28%) relapsed; 42 of 92 (46%) with vascular and/or lymphatic invasion (VLI) in the primary tumour relapsed, whereas only 26 of 151 (17%) without this feature relapsed (P<0.001). VLI was the only identifiable risk factor for relapse in this series. Only one relapse occurred >28 months after orchidectomy. Despite poor compliance in some patients (12%) their survival was not prejudiced. Three patients died from disease despite chemotherapy at relapse. At 17 years and a median follow-up of 53 months, 242 of the 248 men are disease-free and the disease-specific survival rate is 98%. CONCLUSIONS: This study shows that orchidectomy alone and treatment of relapses produces excellent long-term results without the adverse effects associated with retroperitoneal node dissection or elective chemotherapy for high-risk cases.