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The functional ability of PNH reticulocytes was studied by in vitro investigations on reticulocyte-rich suspensions obtained from the blood of eight patients with PNH. The parameter used was the incorporation of 59Fe and of glycine-2-14C, and the results were related to RNA content of the reticulocytes. Iron appeared to enter the PNH cells normally but a relatively small amount was protein bound. In contrast to the behaviour of normal reticulocytes in control experiments, in the PNH reticulocytes there was little or no iron incorporation. The block of haem synthesis was also demonstrated by a four to five fold reduction in incorporation of glycine into haem. Globin synthesis appeared to be unaffected. These findings support the suggestion that in PNH there is a disturbance of the integrated process of cell maturation, demonstrable at the reticulocyte level.

The metabolism of ifosfamide is a delicate balance between a minor activation pathway (4-hydroxylation) and a mainly toxification pathway (N-dechloroethylation), and there remains uncertainty as to the optimal intravenous schedule.This study assesses ifosfamide pharmacokinetics (PK) according to two standard schedules. Using a 1:1 randomized trial design, we prospectively evaluated ifosfamide PK on two consecutive cycles of 3 g/m2/day for 3 days (9 g/m2/cycle) given in one of two schedules either by continuous infusion (CI) or short (3 h) infusion. Highly sensitive analytical methods allowed determination of concentrations of ifosfamide and the key metabolites 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide.Extensive PK analysis was available in 12 patients and showed equivalence between both schedules (3 h versus CI) based on area under the curves (micromol/l x h) for ifosfamide, 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide (9,379 +/- 2,638 versus 8,307 +/- 1,995, 152 +/- 59 versus 161 +/- 77, 1,441 +/- 405 versus 1,388 +/- 393, and 2,808 +/- 508 versus 2,634 +/- 508, respectively, all P0.2). The classical auto-induction of metabolism over the 3 days of infusion was confirmed for both schedules.This study confirms similar PK for both active and toxic metabolites of ifosfamide in adult cancer patients when 9 g/m2 of ifosfamide is administered over 3 days by CI or daily 3-h infusions.

Penile trauma, though rare, requires specialized management. Fibrotic sequelae from lesions of the tunica albuginea and corpora cavernosa must be prevented given their impact of the erectile function. Knowledge of penile anatomy enables acquisition and interpretation of penile MRI, preferably performed in the first few hours following injury. Tear of the tunica albuginea must be identified since it requires surgical management. Other lesions may be present at the acute (hematoma) or chronic (fibrosis, arteriocavernous fistula) phases. MRI, non-invasive and painless, is the imaging modality of choice in the multiplanar evaluation of traumatic injuries of the penis.

Neurological complications are rare in trichinosis. A case of trichinosis involving the central nervous system documented by MRI is presented. To our knowledge, only three cases of neurotrichinosis with MRI abnormalities have been already reported. The physiopathological mechanism are discussed (transport of the parasite through the blood-stream, immuno-allergic reaction or eosinophilic neurotoxic effect).

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenström's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.

14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Societe Francaise d'Oncologie Pediatrique (SFOP). No HIV-positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy-related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period.

Between October 1985 and October 1989, 75 previously untreated patients with stage III and IV non Hodgkin's lymphoma, large cell type, were treated with an alternating weekly chemotherapy regimen including the following drugs: week 1: Doxorubicin, vincristine, cyclophosphamide, bleomycin, and intrathecal (i.th.) methotrexate and cytarabine; week 2: Methotrexate with leucovorin rescue; week 3: Doxorubicin, ifosfamide with mesna, etoposide, and i.th. methotrexate and cytarabine; week 4: Methotrexate with leucovorin rescue. Complete responders after three cycles according to this schedule (12 weeks) were given 18 gys cranial irradiation and randomized between one additional cycle or three monthly CHOP (consolidation treatment). Among 66 evaluable patients, 53 achieved a complete remission (CR 80 per cent) and seven a partial remission (11 per cent). There were six failures, and nine early deaths during the initial phase, mostly due to septic problems. Forty-one of the 53 CR patients (77.3 per cent) have remained free of disease with a median follow-up of 15 months (1-49). Eight of the 12 relapses occurred during the first year, the four others at 13, 14, 16 and 38 months respectively. The 2-year survival was 63 per cent for the whole group, and 77 per cent for the CR group. No difference has been observed up until now between the two groups with different consolidation treatment. Therefore, this protocol seems to be able to produce a high rate of complete and durable remission. The analysis of prognostic factors suggests that some high-risk patients should be considered for intensification therapy with the support of autologous bone marrow transplantation.

Five cases of sarcoidosis associated with malignant lymphoma are reported. In one patient, sarcoidosis was diagnosed several years after the onset of Hodgkin's disease. Of the remaining 4 patients, three developed nodular mixed lymphoma and one immunoblastic lymphoma (complicating angioimmunoblastic lymphadenopathy with dysproteinaemia) 3 months to 12 years after sarcoidosis were diagnosed. Such cases are extremely rare. They may be due to coincidence, but Danish epidemiological data suggest a relationship between the two diseases. Overstepping of humoral immunity in sarcoidosis may induce the emergence of a clone of formerly quiescent neoplastic B-cells.

The authors report a case of major acanthocytosis which regressed spontaneously in a cirrhotic patient. The usual lipid abnormalities: considerable rise in free red cell cholesterol and lesser rise in phospholipid, regressed concommitantly to the disappearance of acanthocytes. No change in the main liver function tests was, however, observed. The etiological mechanisms of acanthocytosis in cirrhosis are probably multiple, and their interactions are compplex. The exchange of abnormal lipoproteins between the plasma and the red cell membrane is the last theory to be considered. On the other hand, no argument could explain the disappearance of the acanthocytosis, this phenomenon is considered up to now irreversible and a sign of the gravity of hepatic lesions.

7 patients with chronic lymphatic leukemia, B type, have been treated with thymic irradiation. A full remission was achieved in 2 and a partial one in 4. No serious complications were noted during or after the irradiation. This treatment has proved efficient even after the failure of a previous chemotherapy and has permitted to resume any other therapeutic modality when the C.L.L. is no more controlled.

Three cases of metastatic malignant thymoma are reported. In all three cases the tumour was invasive and excision was only partial or impossible. Histologically, these tumours were of epithelial origin with a variable lymphocytic component. Metastases were initially present in one case and in the other two developed within the first year. Partial remission was obtained with different drug combinations in only one case, and it was of short duration. The authors emphasize the increased frequency and poor prognosis of these tumours and the need for multiple chemotherapy and loco-regional treatment in the management of invasive thymomas.

In a case of pure megaloblastic refractory anemia, a complete remission is reported. This remission has been obtained by prolonged high dose androgenotherapy and has now lasted for more than 5 years. The practical therapeutic consequences are discussed.

The authors report a case of acute myeloid leukemia developping 5 years after the onset of an autoimmune hemolytic anemia. The cytological origin of the proliferation is difficult to assess: the presence of prominent membranous complexes and a strong positivity of acid phosphatase reaction favour its megacaryocytic origin. However the cytological evolution pleads for the development of successive clones of monocytic origin, may be modified by the treatment. Are the two diseases successive consequences of preexisting state of immunodepression or was such a state created by the autoimmune anemia?

The present report describes 4 Caucasoid families, HLA genotyped, with at least 2 affected siblings suffering from Hodgkin's disease. The affected sibling pairs were identical (2 shared haplotypes) in 2 families and haploidentical (1 shared haplotype) in the 2 others. These results together with the data already published provide evidence for a distortion of the segregation of HLA haplotypes: from a total of 43 pairs of siblings reported, the observed repartition is 22, 15, 6 (2, 1, 0 shared haplotypes respectively) instead of 10.75, 21.5, 10.75 (mendelian repartition). The excess of identical siblings pairs (51% instead of 25%) (p less than 10(-5) confirms the existence of a genetic linkage between the chromosomal HLA region and the susceptibility to the disease.

Unusual giant inclusions are reported in the blast cells during the blastic crisis of a chronic granulocytic leukemia. These inclusions coudl have their origin in degenerated mitochondria, and acid phosphatase positivity suggests fusion with lysosomes. A possible viral etiology is discussed.

The authors report a case of acute myeloid leukemia developing 5 years after the onset of an autoimmune hemolytic anemia. The cytological origin of the proliferation is difficult to assess: the presence of prominent membranous complexes and a strong positivity of acid phosphatase reaction favour its megacaryocytic origin. However the cytological evolution pleads for the development of successive clones of monocytic origin, may be modified by the treatment. Are the two diseases successive consequences of preexisting state of immunodepression or was such a state created by the autoimmune anemia?

Erythroblastopenia occurred in the course of chronic B cell lymphocytic leukemia. The failure of chlorambucil therapy prompted the decision of thymic irradiation. This was effective on the lymphoid proliferation but did not modify the erythroblastopenia. Progressive hepatomegaly led to the diagnosis of hepatoma.

An acute lymphocytic leukaemia develops in a fourteen years old boy, treated five and a half years earlier for an Ewing's sarcoma of the right fibula, by an association of surgery, radiotherapy and chemotherapy. The Ewing's sarcoma is still in remission. Chemotherapy induces easily a complete remission. The authors discuss the links between the two malignancies and their treatment.