Properties of immunotoxins against a glycolipid antigen associated with Burkitt's lymphoma.

A monoclonal immunoglobulin M (IgM) antibody (38-13) which recognizes Burkitt's lymphoma (BL) cells, by reacting with the neutral glycolipid Gal alpha 1 leads to 4-Gal beta 1 leads to 4-Glc beta 1 leads to 1-ceramide, was recently characterized. This monoclonal IgM was coupled to either ricin A chain or gelonin. The two different immunotoxins obtained retained the apparent immunological specificity of 38-13 IgM, as shown by flow cytofluorometry analysis and complement-dependent cytotoxicity test. The BL Ramos cells and the apparently irrelevant Epstein-Barr virus-containing lymphoblastoid Priess cells were used as targets in in vitro assays of the cytotoxic properties of the two immunotoxins by measuring the inhibition of protein synthesis. Isolated ricin A chain, gelonin, and 38-13 IgM exhibited very low intrinsic cytotoxicity on both target cells. 38-13 ricin A chain and 38-13 gelonin conjugates exerted toxic effects on both target cells which were about 6000-fold and 3000-fold higher than uncoupled ricin A chain and gelonin, respectively. The toxicity of these conjugates almost reached that of intact ricin. On Ramos BL cells, the kinetics of action of the 38-13 ricin A chain conjugate was almost as fast as that of intact ricin, because 50% protein synthesis inhibition was reached after 3 hr. In contrast, the kinetics of action in the non-BL Priess was much slower (50% protein synthesis inhibition after 10 hr). An obviously irrelevant immunotoxin (anti-trinitrophenol IgM-ricin A chain) had no significant cytotoxic effect on BL Ramos and non-BL Priess cells. An excess of D-galactose was shown previously to inhibit the 38-13 IgM from binding to the reactive glycolipid antigen bearing a terminal galactose. An excess of D-galactose (0.1 M) inhibited the cytotoxic effect of the two 38-13 immunotoxins, whereas it did not prevent the cytotoxic effect of the anti-trinitrophenol immunotoxin on the same trinitrophenol labeled target cells. These data suggest that the cytotoxic effect observed with 38-13 immunotoxins on non-BL Priess cells was mediated through their binding to a very low number of antigenic sites undetectable by conventional immunological methods. The main characteristics of 38-13 immunotoxins appear to be their fast kinetics of action and the very low number of antigenic sites required for the expression of their toxic effects. These properties could be related to the glycolipid nature of the reacting antigen. Such glycolipid antigens would represent valuable targets for therapeutic use of immunotoxins.

Recurrent cytogenetic abnormalities observed in complete remission of acute myeloid leukemia do not necessarily mark preleukemic cells.

We have undertaken the cytogenetic monitoring of 39 adult patients treated for de novo acute myeloid leukemia (AML) by intensive chemotherapy. We describe this monitoring in seven patients in continuous complete clinical and morphologic remission (CR) of AML. Although in CR, these patients exhibit the emergence of cytogenetically abnormal clones. Abnormalities observed include monosomy 7, del(20)(q11), partial trisomy 1q, and 6p12-22 rearrangements. They correspond to well-known chromosomal rearrangements commonly found in myelodysplasia (MDS), and myeloproliferative syndromes (MPS), as well as AML. Present as the sole detected chromosomal change, they preceded by months the onset of overt leukemia or MDS. In some cases, the abnormal clone showed a proliferative advantage (some patients exhibited up to 100% of abnormal bone marrow metaphases in subsequent analyses). AML relapse, when it occurred, was associated with a different chromosomal modification. Altogether the question arises, whether the abnormalities pointed out in our study (monosomy 7, del(20)(q11), partial trisomy for the long arm of chromosome 1 (q21qter), 6p12-22 rearrangements), and seen after chemotherapy, mark preleukemic cells or not, and whether they participate indirectly, or not at all in the leukemic process.

Variant translocation t(8;21;15) in an acute myeloblastic leukemia with phenotypic differential evolution.

A new case of a variant form of the translocation (8;21) in an AML-M2, including in addition involvement of chromosome #15 is reported. The selection of two abnormal lines, probably resulting from two successive rearrangements of the (8;15) translocated segment, is observed. It is suggested that these rearrangements change the cellular morphology and seem to play a part similar to additional autosomal abnormalities in the course of the disease, such as those found in CML.

Cutaneous T-cell lymphoma in association with a monoclonal gammopathy.

Monoclonal gammopathies and other abnormalities of immunoglobulin production may characterize or frequently be associated with B-cell lymphoproliferative disorders. We describe a patient with a T-cell cutaneous lymphoma, expressed clinically as Sézary's syndrome, in association with an immunoglobulin A type kappa M-component monoclonal gammopathy. No evidence for the coincident presence of a malignant plasma dyscrasia was found. This clinical association may lend clinical support to the concept that Sézary's syndrome is a T-helper-cell malignant proliferation. A colonic carcinoma was also present, possibly representing a second manifestation of a functionally abnormal cellular immune system.

Knee arthritis revealing acute leukemia in a patient with rheumatoid arthritis.

We report one case of leukemic synovitis in a patient with a 40-year history of rheumatoid arthritis. The synovial fluid sample and synovial biopsy specimen showed myeloblastic cells. So, leukemic synovitis can be suspected in a patient with inflammatory rheumatism and adequate diagnostic procedures should be carried out.

Lymphoma developing in a patient with rheumatoid arthritis taking methotrexate.

We report one case of non-Hodgkin lymphoma in a patient, with a 30-year history of rheumatoid arthritis, taking low dose methotrexate weekly over a 10-month period. The mild immunosuppression that occurs with methotrexate therapy probably places patients with rheumatoid arthritis at added risk of developing lymphoproliferative diseases, but coincidence cannot be excluded.

Erythema nodosum and Hodgkin's disease.

Erythema nodosum is an unusual manifestation of Hodgkin's lymphoma. One patient with long remission of Hodgkin's disease manifested persistent erythema nodosum beginning one and three months before relapse was clinically evident. So, the diagnosis of Hodgkin's disease should be considered in patients with unexplained recurrent erythema nodosum.

Paraneoplastic Raynaud's phenomenon.

A testicular tumour could be diagnosed by the occurrence of a Raynaud's phenomenon complicated by severe digital arteritis. The arteritis rapidly regressed under prostacyclin therapy. Such vascular manifestations are frequent in testicular carcinoma, but they usually develop after chemotherapy. To our knowledge, this is the first case where they preceded the diagnosis and specific treatment of a tumour of the testis.

[Hodgkin's disease associated with HIV infection: clinical characteristics and development. French registry of tumors associated with HIV infection]. / Maladie de Hodgkin survenant au cours de l'infection à VIH: caractéristiques cliniques et évolution. Registre français des tumeurs associées à l'infection à VIH.

From May 1987 to July 1990, 45 cases of Hodgkin's disease (HD) were recorded by the French Registry of HIV-associated tumors. Thirty-nine patients were male and median age was 30 years. Twenty-two cases had mixed cellularity type (MC), 18 nodular sclerosis, two lymphocyte depletion and three were not classified. Thirty-four patients had advanced HD clinical stages (CS III and IV). Thirty-six patients (80%) presented with B symptoms. Bone marrow involvement was diagnosed in 12 patients. Mediastinal involvement was present in only 4/30 patients (12%). Risk groups for AIDS were homosexuality in 18 cases, intravenous drug abuse in 17, both in one, and other in nine cases. In 40 cases (89%), HD occurred before any AIDS-related episode. Median CD4 cell count at HD diagnosis was 304 cells/microliters. Seventy-nine percent of the patients achieved complete remission with standard therapy, but hematological and infectious complications were very frequent. The rate of progression to AIDS was 71% at three years and opportunistic infections (mainly pneumocystis carinii pneumonia) were the most frequent cause of death. Overall two-year survival was 41% (78% for patients with initial CD4 cell count higher than 300 cell/microliters and 0% for those with CD4 cell count lower than 300/microliters). HD-HIV has a specific clinical profile as compared to primary HD, with a predominance of MC type and advanced clinical stage, without mediastinal involvement (88%). This study provides a basis for future clinical trials on HD-HIV: intensity of chemotherapy should be adapted to CD4 cell count; pneumocystis carinii prophylaxis is mandatory in all cases. Zidovudine should be included during and after HD treatment; the potential role of hematological growth factors has still to be evaluated.

[Venous thrombosis disclosing Marchiafava-Micheli disease]. / Thromboses veineuses révélatrices d'une maladie de Marchiafava-Micheli.

It is established practice in patients with thromboembolic disease without the classical predisposing factors to search for general causes and abnormalities of blood clotting. The authors report a case of paroxysmal nocturnal hematuria or the Marchiafava-Micheli syndrome, a rare but classical cause of venous thrombosis. In this patient, the hemopathy presented with venous thrombosis.

[Cardiovascular manifestations of Cogan syndrome. Apropos of a case]. / Manifestations cardiovasculaires du syndrome de Cogan. A propos d'un cas.

The authors describe a case of Cogan's syndrome in a patient with ulcerative colitis complicated by several cardiovascular manifestations including bilateral coronary ostial stenosis, rapidly progressive aortic regurgitation and aneurysm of the thoracic aorta, thrombosis of the common iliac artery and pericardial symphysis. This rare form of inflammatory arteritis, the diagnosis of which is usually made on the finding of associated ocular and auditory involvement, is distinct from other types of angiitis by the predisposition to severe cardiovascular complications which influence the vital prognosis. The differential diagnosis with more common collagen diseases with cardiovascular complications is discussed.

[An unusual pericardial tumor: bronchogenic cyst]. / Une tumeur péricardique inhabituelle: le kyste bronchogénique.

The authors report the case of an intrapericardial bronchogenic cyst in a 42 year old woman with no cardiac symptoms. Despite extensive investigation, the final diagnosis was made only at anatomopathological examination. A pericardial localisation of this embryological tumour is very rare and a number of features of the condition are described. In this case, the carbohydrate antigen (CA 19-9) was a veritable marker of this tumour. This association, described for the first time, between a simple biological marker and an intrapericardial bronchogenic cyst, could be a valuable diagnostic aid in a pathology in which surgery could reasonably be deferred should the diagnosis of bronchogenic cyst be certain.

[Cutaneous hemangioma associated with eosinophilia]. / Angiome cutané associé à une éosinophilie.

A patient with a cutaneous angioma developed an intravascular coagulation syndrome with a eosinophilic leukocytosis and multiple arterial and venous thromboses affecting the vital prognosis. The possible role of the eosinophilia in the mechanism of complications is discussed. Local modifications in the angioma are suggestive signs preceding the onset of general thrombotic complications, their severity contrasting with the simplicity of the secondary surgical excision of the angioma.

Pseudoaneurysm of the inferior epigastric artery.

Abdominal wound closure with safety retention sutures can cause intestinal obstruction, fistula, skin necrosis and rarely pseudoaneurysms of the inferior epigastric artery (IEA) (1, 2, 3). We report the case of a man presenting with a pseudoaneurysm of the IEA after traumatic extraction of retention sutures, successfully treated by surgical ligation of the feeding vessels. The importance of contrast enhanced CT and duplex colour Doppler sonography in differential diagnosis of postoperative abdominal wall masses is discussed, as well as possibilities and risks in the treatment of false aneurysms of the IEA.

Axillounifemoral and axillobifemoral bypasses. Retrospective study of 85 cases.

From 1983 to 1990, 65 axillobifemoral and 20 axillofemoral bypasses have been performed in 85 patients (77 men and 8 women), with a mean age of 69 +/- 9 years. Indications for surgery were: severe aortoiliac occlusive disease (87%), sepsis of previous aortoiliac prosthesis, abdominal aorta aneurysm. Anatomic bypass was precluded for general (81%) or local (19%) conditions. In the last group, 9 patients have had previous laparotomy. Four patients presented with aortoenteric fistulas. Eighteen patients were operated on in emergency. The operative mortality was 12%, with 50% cardiac related deaths. Early primary patency was 98%. Early secondary patency was 100%. The mean follow-up is 28 +/- 15 months. The 3 years survival is 77%. The cumulative patency rates at 1 and 3 years are 89% and 76% respectively. Although axillobifemoral bypasses achieve poor long-term results when compared with aortoiliac bypasses, they can be considered in high risk patients. In this group of patients, the cumulative patency rate and the survival curves tend to be parallel.

[Drug-induced benign intracranial hypertension. Apropos of a case with amphotericin B. Review of the literature]. / Hypertension intracrânienne bénigne médicamenteuse. A propos d'un cas rapporté à l'amphotéricine B. Revue de la littérature.

Benign intracranial hypertension (BICH) is a rare adverse event. We report the case of a 31-year-old female drug addict who had been seropositive for HIV since 1987. She had stage IV C1 AIDS, and was receiving intravenous amphotericin B for generalized cryptococcosis with no neuromeningeal involvement. She developed BICH that regressed when the antifungal drug was withdrawn and treatment for cerebral edema was started. BICH is a clinical entity involving intracranial hypertension with no focal neurological signs or detectable intracranial lesion. The manifestations include headache, transitory or permanent visual disturbances (diplopia, loss of visual acuity) and the perception of intracranial noise. The cerebrospinal fluid is under increased pressure but the composition is normal. The eye fundus examination shows papillary edema, and the neuroradiological workup is normal. BICH can only be diagnosed once an expansive intracranial process, neuromeningeal infection, and non-communicative hydrocephalus have been ruled out. In the majority of cases, no etiology is found. Such cases of idiopathic BICH usually occur in overweight young women, although drugs can be implicated. Amphotericin B has not previously been held responsible for BICH. On the basis of this observation, we present a review of the literature.

[Abdominopelvic actinomycosis in pseudo-tumoral form: diagnosis by ultrasonography-guided biopsy]. / Actinomycose abdomino-pelvienne à forme pseudo-tumorale: diagnostic par ponction sous échographie.

The authors report a case of abdominopelvic actinomycosis, a rare bacterial infection. This case is exceptional for its clinical tumoral expression with fistulization through the skin, and for its rapid diagnosis by ultrasonically-guided needle biopsy. The clinical, bacteriological, histological and therapeutic aspects of actinomycosis are detailed.

[Heparin-like anticoagulant in small cell bronchial carcinoma]. / Anticoagulant circulant "heparine like" au cours d'un carcinome bronchique à petites cellules.

Acquired circulating heparin-like anticoagulants may have different causes, the most frequent being plasmocyte proliferation. The authors report an exceptional case of association between an heparin-like inhibitor and a small-cell anaplastic lung carcinoma, and they review the pathogenesis, laboratory diagnostic methods and treatment of the anticoagulant.

[Tyrosine kinase: implications in tumor pathology and therapeutic perspectives]. / Tyrosine kinase: implications en pathologie tumorale et perspectives thérapeutiques.

The tyrosine kinase family includes growth factor receptor and cytoplasmic enzymes. It plays a key role in normal cell division and abnormal cell proliferation and differentiation. The most common tyrosine kinases are the epidermal-growth factor (EGFR) and platelet-derived growth factor (PDGF) receptors, and a chromosome Philadelphia product, the Bcr-abl oncogene. Many studies have attempted to correlate clinical evolution of tumors with tyrosine kinase expression. However, clinical application of these new prognostic factors has not yet been demonstrated. More recently, tyrosine-phosphorylation inhibitors (tryphostin) have been developed in phase I studies. Results that were obtained show some objective responses in patients with glioblastoma and polymetastatic cancer. Another approach to block tyrosine kinase expression is the use of monoclonal antibodies. Trials using such antibodies have shown interesting preliminary results.

[Spinal cord compression of sarcoidosis origin: a case]. / Compression médullaire d'origine sarcoïdosique: une observation.

This observation reports the case of a rapid paraparesia occurring in a young man. Imaging disclosed a spina tumor. Diagnosis of sarcoidosis leads us to suspect a specific spinal granuloma involvement and to start corticosteroid pulses. Clinical and radiological symptoms improved dramatically.