≃10 eV ionization shift in Ir Kα2 from a near-coincident Lu K-edge.

Close to an x-ray filter's K-edge the transmission depends strongly on the photon energy. For a few atom pairs, the K-edge of one is only a few tens of eV higher than a K-line energy of another, so that a small change in the line's energy becomes a measurable change in intensity behind such a matching filter. Lutetium's K-edge is ≃27 eV above iridium's Kα(2) line, ≃63.287 keV for cold Ir. A Lu filter reduces this line's intensity by ≃10 % when it is emitted by a plasma, indicating an ionization shift Δε≃10±1 eV.

K-line spectra from tungsten heated by an intense pulsed electron beam.

The plasma-filled rod-pinch diode (PFRP) is an intense source of x-rays ideal for radiography of dense objects. In the PRFP megavoltage electrons from a pulsed discharge concentrate at the pointed end of a 1 mm diameter tapered tungsten rod. Ionization of this plasma might increase the energy of tungsten's Kα(1) fluorescence line, at 59.3182 keV, enough for the difference to be observed by a high-resolution Cauchois transmission crystal spectrograph. When the PFRP's intense hard bremsstrahlung is suppressed by the proper shielding, such an instrument gives excellent fluorescence spectra, albeit with as yet insufficient resolution to see any effect of tungsten's ionization. Higher resolution is possible with various straightforward upgrades that are feasible thanks to the radiation's high intensity.

Hyaluronidase as additive to induction chemotherapy in advanced squamous cell carcinoma of the head and neck.

Forty-eight patients with advanced head and neck tumours were treated with irradiation and concomitant chemotherapy with cisplatin, vindesine and hyaluronidase. The disease-free survival rate at 5 years was 47%. The toxic effects were mucositis (48 patients), nausea (25 patients, vomiting in six patients), bone marrow depression (15 patients) and peripheral neuropathy (14 patients). The results warrant a randomized trial.

Combined application of cisplatin, vindesine, hyaluronidase and radiation for treatment of advanced squamous cell carcinoma of the head and neck.

In a prospective pilot study, 32 patients with advanced inoperable squamous cell carcinoma of the head and neck were treated with polychemotherapy and hyaluronidase combined with radiation therapy. Polychemotherapy consisted of 5 mg vindesine on day 1 and 80 mg/m2 cisplatin on day 2. The patients were given 200,000 IU hyaluronidase intravenously 20 minutes prior to vindesine and cisplatin. Radiation in fractions of 2 Gy per day was administered on the following days (days 3-5, 8-12, 15-18), that is, 12 times. This regimen was repeated twice starting with day 22 and 43. Side effects were mainly of local character: moderate to severe mucositis in 10 patients and mild mucositis in 22 patients. No severe systemic toxicity was observed. Complete remission was achieved in 27 of 32 patients. At present, 16 patients are alive and without relapse. The average time of follow-up is 47 months (range: 26-75 months). These preliminary results suggest that combined therapy with vindesine, cisplatin, hyaluronidase, and radiation are well tolerated by most patients and highly effective against advanced squamous cell cancer of the head and the neck.

Carboplatin, methotrexate and vinblastin (Carbo-MV) for advanced urothelial cancer. A phase II trial.

Fifteen patients with advanced urothelial cancer were treated with carboplatin 300 mg/m2, methotrexate 30 mg/m2, and vinblastin 3 mg/m2 on day 1 and the same dosage of methotrexate and vinblastin on days 15 and 22. Six patients were pretreated with radiotherapy and or chemotherapy; 7 patients had impaired renal function due to obstructive uropathy. Eight patients achieved a partial remission; 4 patients achieved a minor remission or stabilization of progressive disease. Mean duration of response was 8+ month (2+ to 12+ month). Subjective tolerance of the treatment was excellent but there was considerable bone marrow toxicity in the pretreated patients. The data show that Carbo-MV (carboplatin, methotrexate, and vinblastin) is effective and subjectively well tolerated in advanced urothelial carcinoma.

[Cisplatin, vindesine and hyaluronidase combined with simultaneous radiotherapy of advanced head and neck tumors]. / Cis-Platin, Vindesin und Hyaluronidase in Kombination mit simultaner Strahlentherapie bei fortgeschrittenen Tumoren im Hals- und Kopfbereich.

In a prospective pilot study 21 patients with advanced squamous cell carcinoma of the head and neck were treated with polychemotherapy and Hyaluronidase combined with radiation. With the exception of one patient, who refused laryngectomy, all patients were inoperable. Chemotherapy consisted of 5 mg Vindesine on day 1 and 80 mg/m2 Cisplatin on day 2. 200,000 U Hyaluronidase were given by infusion over 20 min prior to Vindesine and Cisplatin. Radiation in fractions of 2 Gy a day was administered 12 times per cycle (day 3-5, 8-12 and 15-18). Treatment was repeated on day 22 and 43. Total radiation dose was 72 Gy. Side-effects were mainly of local character (moderate severe mucositis in 7, mild mucositis in 14 patients). No severe systemic toxicity was seen. Complete remission was noted in 17 out of 21 patients. 16 patients are now a life without progression. 1 patient in complete remission died 5 months after therapy due to pneumonia without evidence of tumor. The mean time of follow up is 16 months (range 3-42). The preliminary results suggest that combined therapy with Vindesine, Cisplatin, Hyaluronidase and Radiation is well tolerable and highly effective against advanced squamous cell carcinoma of the head and neck.

Elevated superoxide dismutase in Bloom's syndrome: a genetic condition of oxidative stress.

We have found that Bloom's syndrome (BS) cells exhibit elevated levels of superoxide dismutase activity. Since SOD activity has been shown to reflect the intracellular superoxide (O2-) content, these results indicate that BS cells exhibit oxidative stress which ultimately results in DNA damage. Elevated sister chromatid exchange, the major cytological characteristic of BS, and superoxide dismutase induction were simulated in normal lymphoblastoid cells by treatment with compounds that increase the steady-state concentration of O2(-.). The sister chromatid exchange response of a BS lymphoid cell line was modulated through the control of the endogenous O2-. content. We therefore suggest that a major biochemical defect resulting from this genetic disorder is chronic over-production of the superoxide radical anion. The consequence of high O2-. levels concomitant with induced superoxide dismutase activity is the formation of enormous amounts of H2O2 which can apparently inactivate the enzymes responsible for its elimination. The inefficient removal of peroxide can result in high rates of sister chromatid exchange and chromosomal damage in BS cells and in normal cells treated with oxidation-reduction cycling compounds through the formation of highly reactive intermediary forms of active oxygen.

A t (11;21) (13;q22) in Ph-positive chronic myelogenous leukemia.

Reciprocal translocations, in addition to that of the Ph chromosome, though rare, have been reported in chronic myelogenous leukemia (CML). We describe here a case of Ph-positive CML with a new translocation, t (11;21) (q13;q22), and missing Y, which were present both during transformation to the blastic crisis and in the subsequent reversion to the chronic phase. The possible significance of this abnormality is discussed.

Translocation t(6;9)(p22.3;q34) in myelodysplastic syndrome--refractory anemia with excess blasts.

A 69-year-old male patient with refractory anemia with excess blasts (RAEB) was found to have a consistent chromosomal abnormality, t(6;9)(p22.3;q34), in the bone marrow and unstimulated peripheral blood cells. Twenty patients with t(6;9) and leukemia have been reported; some of them had a myelodysplastic syndrome (MDS) before developing overt ANLL. Our patient was still in the MDS stage when the t(6;9) was found. This result suggests that t(6;9) represents one of the pathways from MDS to leukemia in patients with ANLL.

Effect of mitochondrial inhibitors on metaphase-telophase progression and nuclear membrane formation in Chinese hamster cells.

Chinese hamster Don cells in log-phase were exposed to Colcemid during the G2 period with and without a combination of divalent cation chelators and mitochondrial inhibitors. Isolated metaphase cells were incubated as follows: (i) without Colcemid but with other agents and the progression was monitored from metaphase (M) to telophase (Tel) and to cell division; (ii) with Colcemid and other agents and the rate of micronuclei formation in the absence of anaphase was studied. Both EDTA and EGTA accelerated the progression from M to Tel, but did not affect the overall rate of cell division. Chloramphenicol (CAP), an inhibitor of mitochondrial protein synthesis, blocked the effect of the chelators and also retarded the progression. An inhibitor of mitochondrial respiration, Antimycin A (AA), also retarded the progression in the absence of the chelators and prevented the promoting effect of the chelators. A stimulator of ATPase for ATP breakdown. 2,4-dinitrophenol (DNP), accelerated the M to Tel progression. Chloramphenicol (CAP) and AA, as well as DNP, appeared to have little effect on the formation of micronuclei in the presence of Colcemid. EGTA, which affects cell surface Ca2+, stimulated the formation of micronuclei. This study indicates that Ca2+ ions and mitochondrial function are involved in the regulation of a certain segment of mitosis beyond metaphase, with Ca2+ sequestration in the mitochondria and chelation of Ca2+ by EGTA as dominant factors.