Drivers of rare earth elements (REEs) and radionuclides in changing subarctic (Nunavik, Canada) surface waters near a mining project.

The emergence of mining projects for rare earth elements (REEs) in response to rising global demand and geopolitical factors introduces environmental concerns, such as the suspected release of anthropogenic REEs to aquatic systems and the coexistence of radionuclides (U, Th). Northern regions confront heightened challenges from limited research and accelerated climate change. Drivers of REEs in surface waters (including George and Koroc rivers, their tributaries, and thermokarst lakes) were studied (2017-2023) in subarctic Canada within a climate transition zone, near a prospective REE mine. Dissolved REEs (<0.45 µm) correlated positively with Al, Fe, Th, U, Cl- and DOC. A novel relationship with water temperature demonstrated an approximate 10-fold decrease in REE concentrations over the environmental gradient (2-20 ℃), suggesting complex implications for REE speciation under climate pressures. Optical analyses further predicted REEs were mobilized by humic-rich, terrestrial DOC, with correlations presenting a possible co-transport with Al, Fe and Th. Relationships for redox-sensitive Ce anomalies (Ce/Ce* = 0.18-1.2) with multi-valent trace metals (Al, Fe, Ti) and DOC were suggestive of a preferential adsorption of Ce by inorganic colloids in low-DOC systems. Findings emphasized the potential for changes in REE geochemistry with ongoing northern surface warming and vegetation shifts.

Doxorubicin plus metronidazole in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck.

Twenty-five patients were treated on a Phase II study of doxorubicin, 60-75 mg/m2 intravenously every 3 weeks, accompanied by metronidazole, 1500 mg/m2 orally 12 hours and immediately before the doxorubicin and 6 hours and 24 hours after the doxorubicin. Of 23 patients evaluable for response, 2 (9%) achieved complete remissions, 2 (9%) achieved partial remissions, and 4 (18%) were stable (one of whom achieved a minor response). One patient with an inoperable biopsy-proven 4 x 3 x 3 cm recurrence following radiation and surgery has had a complete remission that persists at 8 years. The second patient who achieved a complete remission subsequently underwent surgical resection of the involved area. No residual tumor was found, and he remains disease free after 8.5 years. Doxorubicin toxicity did not appear to be augmented significantly by metronidazole. Although the response rate seen in this study was low, the occurrence of two long-term complete remissions suggests that this combination should be studied further in other tumor types.

Cisplatin, cytosine arabinoside, and pentoxifylline in the treatment of squamous cell carcinoma of the head and neck.

Nine patients were entered on a Phase I-II study of cisplatin, cytosine arabinoside, and pentoxifylline in the treatment of advanced head and neck cancer. The treatment regimen consisted of cisplatin 100 mg/m2 intravenously on day 1 only, cytosine arabinoside 2,000 mg/m2 intravenously on days 1 and 2, and pentoxifylline 400 mg orally three times daily beginning 7 to 14 days before the chemotherapy. The pentoxifylline was continued between chemotherapy cycles. Chemotherapy courses were repeated at 3- to 4-week intervals. Partial remission were seen in two patients, two patients were stable, and five patients failed on treatment. Dose-limiting toxicity was granulocytopenia. Pentoxifylline itself caused some nausea and anorexia. Although the patient numbers were small, there was no indication that pentoxifylline increased the efficacy of this chemotherapy in head and neck cancer. It is possible that another dose schedule might have been more effective.

Cisplatin plus cytosine arabinoside in the treatment of squamous cell carcinoma of the head and neck.

Twenty-seven patients with squamous cell carcinoma of the head and neck were treated with i.v. cisplatin 50-100 mg/m2 followed by a rapid infusion of cytosine arabinoside 500-4,000 mg/m2. All except four of the patients had received prior irradiation and six had had prior chemotherapy. There was one early death. Of 25 evaluable patients, one (4%) achieved a complete remission and 10 (40%) achieved partial remissions lasting 6-50 weeks (median, 16 weeks). Ten patients (40%) were classified as having stable disease, including five (20%) who experienced minor responses lasting 5-8 weeks. Four patients (16%) had progressive disease. Drug doses, patient performance status, and prior exposure to chemotherapy did not appear to alter the response rate. Gastrointestinal toxicity was severe in some patients. Myelosuppression tended to be unpredictable and variable within individual patients and was not clearly related to drug doses. Two patients had generalized seizures and one became confused while hypomagnesemic. Renal toxicity, ototoxicity, and paresthesias were seen only at a cisplatin dose of 100 mg/m2. One patient developed stomatitis and one had an allergic reaction to cisplatin. There was one possible drug-related death. This regimen is reasonably well tolerated and may be somewhat more active than cisplatin alone, although further studies are needed to confirm it. Further studies involving additional doses of high dose cytosine arabinoside following cisplatin could also be worthwhile.

Methotrexate and 5-fluorouracil in the treatment of squamous and other carcinomas of the head and neck.

Thirty-two patients with squamous cell carcinomas of the head and neck and three patients with parotid gland carcinomas were treated with methotrexate 40 mg/m2 followed 1 h later by 5-fluorouracil 600 mg/m2. Treatments were repeated on day 8, then every 2 weeks, toxicity permitting. Of 30 evaluable patients with squamous cell carcinomas, 9 (30%) achieved a partial (8) or complete (1) remission. Performance status and prior treatment history appeared to affect the probability of response. The original site of the primary had no apparent effect on response rate. Six patients having objective tumor regression but less than the amount required for classification as partial remission all had marked symptomatic relief and had "response" durations and survivals quite comparable to those in patients achieving partial remission. One patient with a parotid gland carcinoma attained a complete remission, one had a minor response, and one refused to return for follow-up. Myelosuppression and stomatitis were dose-limiting in some patients, although the regimen was generally well tolerated. Three patients (9%) developed cerebellar toxicity, suggesting that prior ethanol abuse could possibly predispose to this side effect.

Penetration of VP-16 (etoposide) into human intracerebral and extracerebral tumors.

VP-16 100 mg/m2 was given intravenously to 10 patients undergoing surgical resection of intracerebral tumors, and the drug was assayed in resected tumor using high pressure liquid chromatography. VP-16 concentrations varied from undetectable (less than .1 microgram/g) to 5.9 micrograms/g (mean, 1.4 microgram/g). VP-16 concentrations in tumors were lower than concurrent plasma concentrations. In addition, intracerebral tumors had a lower concentration of VP-16 than did extracerebral tumors (mean VP-16 concentration, 3.9 micrograms/g) from 7 patients receiving VP-16 50-100 mg/m2 intravenously. Plasma pharmacokinetics of VP-16 were different in our patients with intracerebral tumors than in previously studied patients with extracerebral tumors and it is unclear what role this may played in variability of tumor VP-16 concentrations. VP-16 concentrations were similar in glioblastomas and brain metastases. Specimens from patients with small cell undifferentiated carcinoma of the lung had the highest VP-16 concentrations. A patient who had both viable and necrotic tumor resected during an occipital lobectomy had a higher drug concentration in the necrotic than in the viable area of tumor. In addition, VP-16 concentration decreased as a function of distance into brain from the tumor. Based on our data, VP-16 might be expected to have less activity against intracerebral than against extracerebral human tumors.

Intravascular angiomatosis of the pharynx (Masson's vegetant intravascular haemangioendothelioma)--a case report.

A case of intravascular angiomatosis arising in the pharynx of a 30-year-old man is reported. Gross and microscopic features with differential diagnosis are discussed. The importance of recognition of the lesion as a benign lesion which can arise in the pharynx is stressed.