Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.

Demonstration of Chlamydia trachomatis in inguinal lymphadenitis of lymphogranuloma venereum: a light microscopy, electron microscopy and polymerase chain reaction study.

Intravacuolar organisms in vacuolated macrophages were associated with areas of necrosis and suppuration in 12 patients with suppurative inguinal lymphadenitis. The intravacuolar organisms measured 0.2 to 2.0 micrometers in diameter, stained Gram negative with the Brown-Hopp's tissue Gram stain, faintly blue with hematoxylin and eosin stain, and black with the Warthin-Starry silver impregnation stain. The organisms lined vacuolar membranes and/or clumped in centers of vacuoles. Electron microscopy revealed elementary and reticulate bodies and intermediate forms characteristic of the genus Chlamydia. Cultures of three lymph nodes in McCoy cells grew Chlamydia trachomatis, lymphogranuloma venereum (LGV) serovars. Polymerase chain reaction using primers for chlamydial 16S ribosomal DNA confirmed the organisms as Chlamydia in lymph nodes from nine patients. Recognition of chlamydial organisms by light microscopy in tissue sections of lymph nodes allows a definitive diagnosis of lymphogranuloma venereum.

Whipple's disease presenting as chronic wastage and abdominal lymphadenopathy.

We describe a 24-year-old man who presented with chronic wastage and massive abdominal lymphadenopathy which strongly resembled a malignant neoplasm. Biopsy of mesenteric lymph nodes with ancillary studies led to the correct diagnosis of Whipple's disease. These symptoms began 2 months after the patient returned from military service in the Persian Gulf.

Immunohistochemical and electron microscopic profiles of cutaneous Kaposi's sarcoma and bacillary angiomatosis.

Thirty cases of cutaneous Kaposi's sarcoma (KS) were evaluated and compared with eight cases of acquired immunodeficiency syndrome (AIDS)-related bacillary angiomatosis (BA). The morphologic features of both lesions were studied by light and electron microscopy and by immunohistochemistry with monoclonal endothelial antibodies against CD34, BNH9, and factor VIII-related antigen as well as the lectins Ulex europaeus 1 and Psophocarpus tetragonolobus. Macrophage/monocyte markers used were alpha 1-antitrypsin, lysosome, Kp1 (CD68), and polyclonal factor XIIIa. Electron microscopic studies demonstrated that most of the spindle cells in KS showed a paucity of cell organelles and an absence of Weibel-Palade bodies (WPB), whereas the cells in BA showed activated endothelial cells with WPB. By immunohistochemistry the spindle cells in KS were consistently positive for CD34 only, whereas proliferating cells in BA expressed all endothelial markers used. Numerous cells expressing macrophage/monocyte markers were present surrounding both KS and BA, and a small number of similar cells were entrapped within both lesions. The results demonstrated a restricted immunohistochemical profile for endothelial cell markers in spindle cells of KS (CD34+) distinct from that of endothelial cells in BA. These findings suggest that the spindle cells in KS are poorly differentiated endothelial cells or that they belong to an endothelial cell subset with partial expression of endothelial phenotype.

[A specific prescription of lithium in different neurotic states or in normal subjects with transient dysthymic states]. / A propos d'une indication particulière du lithium dans certains états névrotiques, ou chez des sujets normaux présentant des états dysthymiques transitoires.

Among inapparent cyclothymic patients, love despair is frequently seen as basis or result of a severe thymic decompensation. Lithium is the recommended therapy for these critical states.

Sequential changes of alpha1-antitrypsin after surgical trauma.

alpha1-Antitrypsin, an acute phase reactant, is known to rise following surgery [1,2]. It has not been previously reported, however, that the rise is preceded by an initial drop. Our study on a large group of surgical patients confirms the rise, but also shows that a significant drop in alpha1-antitrypsin levels occurs prior to the increase, if the serum samples are obtained immediately after completion of surgery. The observed decrease was independent of age, sex, type of surgery performed or the anesthetic administered. It is postulated that the decrease in serum levels is the result of migration of alpha1-antitrypsin to the tissues injured during surgery.