The effect of immunoadsorption with the Immusorba TR-350 column on coagulation compared to plasma exchange.

BACKGROUND AND OBJECTIVES: Plasma exchange (PE) and immunoadsorption with the Immusorba TR-350 column (IA) are used to remove autoantibodies from plasma in acute neurological autoimmune disorders. The impact of IA on coagulation and on low molecular weight heparin (LMWH) levels in comparison with PE was investigated. PATIENTS AND METHODS: In five patients with neurological autoimmune disorders, coagulation parameters (global tests, coagulation factors) were measured before and after PE or IA (Part A). In five other patients under anticoagulation with LMWH, anti-Xa activity and global tests were measured before and after the treatments (Part B). RESULTS: After PE, coagulation factors were significantly reduced by 50-70%. After IA, a distinct reduction was observed for fibrinogen, but not for antithrombin and most of the other coagulation factors. Anti-Xa activity was reduced after PE (from 0.57 ± 0·10 to 0.13 ± 0.05 IU/ml) and almost unchanged after IA. CONCLUSION: It is advisable to discontinue or to reduce LMWH doses and to monitor coagulation parameters and anti-Xa activity after PE or IA to decide about further LMWH dosing.

[Malignant dermohypodermic melanoma of the soft tissues]. / Mélanome des tissus mous dermohypodermique.

INTRODUCTION: Melanoma of the soft tissue is a rare tumor that develops in most cases in the deep structures, only rarely involving the skin surface. We report an exceptional case of melanoma of the superficial soft tissue, exclusively involving the skin surface. OBSERVATION: A 35-year-old man presented with a superficial, pink, soft, mobile, lesion on the thigh. The histological examination revealed a tumoral proliferation of the reticular dermis and hypodermis, composed of pale giant cells grouped in nests or in lobules separated by connective ducts. Immunostaining was positive for HMB45, protein S-100, vimentine and NKIC3. It was negative for EMA, CD34, smooth muscle actin, cytokeratine and desmine. The search for a metastatic localization was negative. Extensive exeresis was performed. Three years later, the patient was still in complete remission. The macroscopic, histological and immunohistochemical examinations concluded in the diagnosis of a strictly dermohypodermic melanoma of the soft tissues. DISCUSSION: Our case report of a melanoma of the soft tissues is original because of the superficial localization of the tumor that, to our knowledge, has never been reported. It underlines the interest of performing systematic biopsies of any fast growing cutaneous lesion of recent discovery.

[Spironolactone-induced pemphigoid]. / Pemphigoïde induite par la spironolactone.

BACKGROUND: Sporadic observations would suggest that certain drugs play a role in the development of pemphigoid. A recent case-control study on long-term drug use associated with pemphigoid was unable to confirm the suspected role of these drugs, but did demonstrate a significant association between the development of pemphigoid and use of spironolactone. CASE REPORT: An 82-year-old patient had bullous erythematous lesions on the left thigh suggestive of pemphigoid. Histology and direct cutaneous immunofluorescence confirmed the diagnosis. The patient had been taking alimemazine, adrafinil, flunarizine, spironolactone and furosemide as long-term treatment. Spironolactone alone was withdrawn. The cutaneous lesions regressed and have not recurred during the 18-month follow-up. DISCUSSION: The causal effect of spironolactone in this case of pemphigoid is quite plausible. This hypothesis is favored by the agreement with epidemiological data. Other observations are however required before the causal role of spironolactone in development of pemphigoid can be confirmed.

[Tumoral sarcoidosis]. / Sarcoidose tumorale.

INTRODUCTION: We report here an unusual tumoral form of cutaneous sarcoidosis which lead to diagnostical difficulties. CASE REPORT: A 56 year-old woman was hospitalized for a large lumbo-sacral tumor which size had rapidly increased. The tumor was purplish-red, firm, measured 10 x 20 cm and the patient was unable to sit normally. The biopsies demonstrated a dermohypodermal epithelioid and giant cell granuloma without necrosis. We ruled out an infectious granuloma and a foreign body granuloma. There were no extra-cutaneous localizations. This sarcoidal tumor cured with systemic corticosteroids. DISCUSSION: Tumoral cutaneous forms of sarcoidosis are uncommon; 3 other cases of the literature are reported. Before to state positively this forms it is obligatory to rule out all the other aetiologies of sarcoidal granuloma. The existence of extra-cutaneous localizations and multiple skin localizations is helpful to diagnose this uncommon type of sarcoidosis.

Comparison of the activity of doxorubicin analogues using colony-forming assays and human xenografts.

The potential use of nude mouse xenografts as a source of human tumor tissue for preclinical assessment of drug activity was examined by a comparison of in vitro sensitivity to four anthracycline derivatives of eight xenografts maintained in nude mice and tumor colony-forming units (CFU) from the xenografts grown in agar. Results obtained in the two systems with doxorubicin (Dx) and a new, closely related derivative (epi-doxorubicin, epi-Dx) correlated well. In vivo tumor growth delay and maximum in vitro tumor CFU kill for these two drugs showed a significant correlation (r = 0.64, P less than .01). Separation of tumors into "sensitive" and "insensitive" tumor populations on the basis of maximum in vitro CFU kill also predicted the in vivo response to these two drugs in 88% of cases. Similar analyses performed on in vitro and in vivo results with two other new anthracyclines (4'-deoxy-doxorubicin, deoxy-Dx and 4'-O-methyl-doxorubicin, O-Me-Dx) showed a significant negative correlation between in vivo and in vitro results; the in vitro system failed to predict in vivo activity of these two drugs. No significant differences in in vitro activity against normal, granulocyte/macrophage progenitors (CFU-GM) or against various tumor CFUs were detected. Thus, the selectivity (activity against normal tissue compared with that against tumor) of the four drugs appeared equal. These data suggest that in vitro screening of drugs using tumor CFUs from nude mouse xenografts may predict the in vivo activity of drugs for which pharmacologic data are available, but illustrate the difficulties in attempting to predict the in vivo activity of new drugs for which no such data are available.

In vitro growth and drug sensitivity of tumor colony-forming units from human tumor xenografts.

To investigate the feasibility of using tissue obtained from human tumor xenografts for in vitro screening of antineoplastic agents, we grew human tumor colony-forming units (CFU) in semisold agar from xenografts serially passaged in nude mice. Growth of human tumor CFU was accomplished from nine xenografts representing five different histological tumor types (ovarian carcinoma, adenocarcinoma of the colon, malignant melanoma, epidermoid carcinoma of the lung, and malignant astrocytoma). Cloning efficiency ranged from 0.04 to 0.1% and showed significant variability both between tumor types and between individual animals bearing the same type of xenograft. A high percentage of tumor CFU was in S phase [47 +/- 20% (S.D.)] as determined by the thymidine "suicide" technique. The number of tumor CFU observed increased linearly with increasing numbers of cells plated. In vitro drug sensitivity of the tumor CFU was assessed to Adriamycin, cis-platinum, and melphalan. The patterns of drug sensitivity were found to be reproducible and stable over a period of 9 months. Drug sensitivity curves to Adriamycin for five xenografts representing four tumor types showed complex patterns with plateau portions similar to those described for tumor CFU from primary tumors. The rank order of sensitivity of the tumors was compared to that of normal granulocyte-macrophage progenitors and, with the exception of the melanomas, was found to correlate well with clinical experience (order of sensitivity = colon less than ovary less than bone marrow). Growth of human tumor CFU from xenografts represents a reproducible and stable means for the study of the biology of tumor CFU and has potential applications as a means for screening new anticancer agents.