Hairy cell leukemia presenting as localized skeletal involvement.

We report a 45-year-old man who presented with localized skeletal involvement as the initial manifestation of hairy cell leukemia (HCL) without abnormal peripheral blood counts, splenomegaly or posterior iliac crest bone marrow involvement. The patient presented with pain in the left thigh. A plain radiograph was normal, but a magnetic resonance imaging (MRI) of this region showed a marrow-based lesion occupying the left femur neck, left proximal femur and both greater trochanters.

Rotator cuff tear: clinical experience with sonographic detection.

Between June 1986 and April 1988, 86 sonographic examinations of the shoulder were performed on patients suspected of having rotator cuff tears. Major sonographic diagnostic criteria included (a) a well-defined discontinuity usually visible as a hypoechoic focus within the cuff, (b) nonvisualization of the cuff and (c) an echogenic focus within the cuff. Seventy-five patients underwent both sonography and arthrography.

The effect of glutathione (GSH) depletion in vivo by buthionine sulfoximine (BSO) on the radiosensitization of SR 2508.

The effect of glutathione depletion (GSH) on the efficacy of SR 2508 was evaluated in two murine tumor models with single large doses of radiation or with low doses administered in an accelerated fractionated schedule. To deplete tumor GSH, buthionine sulfoximine (BSO) was administered in the animals drinking water (10 mM) following two i.p.

Antitumor activity and murine pharmacokinetics of parenteral acronycine.

The lipophilic antitumor alkaloid acronycine (ACRO) was solubilized in the cosolvent system used for etoposide. ACRO in this etoposide diluent (VPD) was found to be cytotoxic (less than or equal to 50% colony formation in soft agar) in fresh human tumors from patients with renal cell cancer, ovarian cancer, uterine cancer, and metastatic tumors of unknown primary. In P-glycoprotein-positive, multidrug-resistant (MDR) cell lines, ACRO in VPD was active in MDR Chinese hamster ovary cells but not against MDR L1210 murine leukemia cells, 8226 human myeloma cells, or human CCRF-CEM lymphoblasts.

H2-antagonists and carmustine.

The highly metabolized nitrosourea carmustine (BCNU) is an anticancer agent which alkylates DNA and is metabolized to both active and inactive species by cytochrome P-450 enzymes. Other highly metabolized anticancer drugs have altered toxicities when some histamine H2 antagonists are coadministered. To test this hypothesis with BCNU, DBA/2J male mice were given a single injection of cimetidine (CMT 100 mg/kg) or ranitidine (RNT 25 mg) at various times up to 30 min before, or up to 60 min after a BCNU injection.

Lack of enhanced antitumor efficacy for L-buthionine sulfoximine in combination with carmustine, cyclophosphamide, doxorubicin or melphalan in mice.

A series of studies was performed in tumor bearing mice to evaluate the impact of glutathione (GSH) depletion by L-buthionine sulfoximine (L-BSO). L-BSO doses of 50 or 500 mg/kg were used alone or with one of 4 sulfhydryl-dependent anticancer agents (SHDAA). When L-BSO was administered to tumor-bearing mice, Colon 38 cells were significantly depleted of GSH content, but this did not occur with P388 cells or MOPC-315 cells in vivo.

Cimetidine enhances cisplatin toxicity in mice.

The combination of the histamine H2 antagonist cimetidine (CMT) and the anticancer agent cisplatin (CDDP) was studied in normal and tumorbearing mice. CMT doses of 100 mg/kg produced no alteration in the survival of DBA/2J mice bearing P388 leukemia treated with CDDP doses of 3 mg/kg or 6 mg/kg. In these groups, the median survival was 13 days and 16 days, respectively, compared to 10 days in untreated controls.

Efficacy of sodium thiosulfate as a local antidote to mechlorethamine skin toxicity in the mouse.

The highly vesicant nature of the alkylating anticancer agent mechlorethamine (HN2, or nitrogen mustard) requires careful i.v. technique during its administration.

Experimental dacarbazine antitumor activity and skin toxicity in relation to light exposure and pharmacologic antidotes.

Decarbazine (DTIC) is reported to exhibit enhanced clinical toxicity and increased antitumor activity in vitro when exposed to light. Since it was unclear whether light exposure enhanced DTIC antitumor activity or local toxic effects in vivo, a series of experiments was performed in mice given DTIC solutions exposed to light for 2 hours at room temperature. Adenocarcinoma 07/A was implanted by trocar in adult female BALB/c mice.

Lack of enhanced myelotoxicity with buthionine sulfoximine and sulfhydryl-dependent anticancer agents in mice.

The lethal and non-lethal effects of L-buthionine-SR-Sulfoximine (BSO) with the sulfhydryl-dependent anticancer agents (SHDAA) were investigated in mice. The agents studied included carmustine (BCNU), cyclophosphamide (CTX), doxorubicin (DOX) and melphalan (LPAM). It was shown in normal mice that BSO is nontoxic when given IP or PO at a dose 5 g/kg.

Dose-dependent skin ulcers in mice treated with DNA binding antitumor antibiotics.

The DNA-binding agents daunomycin (DAU-NO), mithramycin (MITH), dactinomycin (ACT-D), amsacrine (mAMSA) and esorubicin (ESO) were tested for local vesicant potential in a quantitative intradermal mouse skin model. Only MITH, which adlineates but doses not intercalate DNA, did not produce dose-dependent skin ulcerations in the mouse. The anthracycline antibiotics DAUNO and ESO produced the largest skin ulcers when administered intradermally at clinically relevant doses (adjusted on the basis of comparable body surface areas).

Mitomycin C skin toxicity studies in mice: reduced ulceration and altered pharmacokinetics with topical dimethyl sulfoxide.

A series of toxicologic and pharmacokinetic studies were performed in BALB/c mice administered intradermal (ID) mitomycin C (MMC) at doses of .015 to 0.25 mg.

Interaction of cimetidine but not ranitidine with cyclophosphamide in mice.

A series of experiments in DBA/2J mice evaluated the biological and pharmacokinetic interactions of the alkylating agent cyclophosphamide (CTX) and the histamine-H2 antagonists cimetidine (CMT) and ranitidine (RNT). Doses were adjusted to approximate human dose levels: 100 mg/kg for CMT; and 25 mg/kg for RNT. CMT reduced the survival of normal (bone marrow stem cell) colony forming units in a dose dependent fashion.

Lack of experimental vesicant activity for the anticancer agents cisplatin, melphalan, and mitoxantrone.

Cisplatin and L-PAM are DNA-crosslinking anticancer agents which have not been systematically studied for vesicant potential. Mitoxantrone is a new active anthracene-based, DNA intercalator which is undergoing widespread clinical testing for antitumor efficacy in man. These three agents were tested for vesicant activity in dehaired BALB/c mice given ID injections equivalent to human clinical doses.

Cytotoxic effects of glutathione synthesis inhibition by L-buthionine-(SR)-sulfoximine on human and murine tumor cells.

The glutathione (GSH) synthesis inhibitor, buthionine sulfoximine (BSO) was tested for cytotoxicity and thiol depletion in murine and human tumor cells in vitro, and for its antitumor activity and toxicity in vivo. The cell lines used in these studies included murine L-1210 leukemia, human RPMI 8226 myeloma, MCF-7 breast cancer and WiDr colon carcinoma. Soft agar colony forming assays showed that BSO was most effective at reducing tumor colony formation when exposed continuously to cells in vitro.

Ethanol increases opioid activity in plasma of normal volunteers.

The effect of acute ethanol administration on plasma levels of beta-endorphin-immunoreactivity and opioid activity was measured in 4 normal volunteers. 60 min following ethanol consumption opioid activity levels, measured by radioreceptorassay, increased significantly with peak rises of more than 400%; levels of beta-endorphin-immunoreactivity did not change significantly. These results are compatible with the effect of the opiate-antagonist naloxone, reversing ethanol-induced coma.