Differential pattern in circulating nitrogen derivatives, lactoferrin, and anti-lactoferrin antibodies in HIV type 1 and HIV type 2 infections.

HIV-1 infection is associated with a dramatic reduction in antioxidative molecules both at the cellular level and in the circulation. This is particularly so for lactoferrin, an iron-binding protein involved in natural defenses (antimicrobial and antiviral activities, etc.) and found in whole secretions, including milk and mucus. In addition to its ability to chelate iron ions, lactoferrin inhibits hydroxy radical formation and interacts with nitric oxide (NO). Levels of plasma lactoferrin decreased in HIV-1-infected patients in correlation with progression of the disease, and highly specific anti-lactoferrin autoantibodies increased. This profile was specific to HIV-1 infection; it was not found in HIV-2-infected patients. In parallel with the drop in lactoferrin, a marked increase in circulating nitrogen derivatives was observed in HIV-1-infected patients, whereas low levels were found in normal donors and in HIV-2-infected patients. These data suggested hyperstimulation of the NO pathway throughout HIV-1 but not HIV-2 infection. This overproduction of NO could play an important role in the development of AIDS symptoms and signs.

Clinical and biological characteristics of human immunodeficiency virus-infected and uninfected intravascular drug users in Ho Chi Minh City, Vietnam.

To define the medical characteristics of intravascular drug users in Ho Chi Minh City, Vietnam, we examined 280 men, of whom 235 were infected with human immunodeficiency virus (HIV), being treated in a rehabilitation center. The patients used mainly opium, often in shooting galleries (50%). The prevalence of oral candidiasis (58%) and zoster infection (20%) was high in HIV-seropositive patients, whereas oral hairy leukoplasia and Kaposi's sarcoma were absent. The prevalence of acquired immunodeficiency syndrome was 24%. More than 80% of the patients had infections with hepatitis C virus, hepatitis B virus, cytomegalovirus, or human T cell lymphotropic virus type-1. The CD4+ cell counts correlated well with viral load. Only HIV-1 subtype E was detected in the 30 patients tested. A cohort study of HIV-infected subjects in this population seems feasible, and would permit introduction of anti-retroviral therapy The large number of HIV-seronegative subjects sharing the same at-risk practices as the HIV-infected subjects raises the possibility of natural protection in this population.

Interaction of mitoxantrone with heparin and its application to the quantitation of heparin.

The interaction of heparin of high molecular weight with mitoxantrone, an anthraquinone derivative, had been studied by spectrophotometry. Heparin links the mitoxantrone and the binding sites are probably the anionic groups of the mucopolysaccharide since the linking is displaced by Na+. This interaction of mitoxantrone with heparin could provides a sensitive and simple method for quantitation of heparin in non proteic medium and could appear of clinical relevance in some circumstances.

Non epidermotropic cutaneous lymphoma ending in leukemia. A case of adult T cell lymphoma (ATL) in France?

A case of uncommon non Hodgkin malignant lymphoma with initial skin involvement is reported. The pathological pattern does not come under standard classifications. An aspect of non epidermotropic diffuse pleomorphic lymphoma is observed. In an immunological cell membrane study, the T-cell lineage of the malignant proliferation exhibited a very unusual pattern including the presence of the E rosette receptor and the expression of HLA-DR monomorphic determinant. This type of T cell malignant lymphoma can probably be included in the group of adult T cell leukemia/lymphoma (ATL) which is endemic in South Western Japan and occasionally observed in Western countries. The emergence of such cases in these countries raises important epidemiological questions.

Cancer chemotherapy induces a transient increase of serum-iron level.

Twenty eight consecutive patients with advanced solid malignancies were studied for variations in serum iron level after a first course of chemotherapy. Eleven different schedules involving twelve drugs were administered. Serum-iron level and serum siderophyllin, hemogram, reticulocytes, inflammatory tests, hemolysis parameters and hepatic enzymes were evaluated before treatment and around the fourth, twelfth and twenty first day after. Response to treatment was measured in all patients. In each patient, regardless of the sex, nature of the tumor or drugs administered, a high increase of serum-iron level was observed between the third and the seventh day after the start of treatment (mean: +263%, range: 78-953%). In twenty one patients, sideremia overstepped the normal range. This variation of serum iron level was transient and the level of sideremia approached the initial rate when it was measured around the thirteenth day after the start of treatment. This phenomenon did not appear to be related to tumor lysis, hemolysis, liver cytolysis or improvement of the inflammatory syndrome. The constant observation of reduction in reticulocytes concurrent with the increase in serum-iron, suggests a mechanism involving impairment of the reticulo-endothelial cells implicated in iron metabolism, due to anticancer drugs. Among the drugs used in this study, actinomycin D, adriamycin, cyclophosphamide and 5-fluorouracil seem to be imputed in the phenomenon observed.

Intraarterial infusion of carboplatin in the treatment of malignant gliomas: a phase II study.

Twenty-three previously treated patients with malignant gliomas were included in this phase II study of carboplatin (400 mg/m2) given as an intraarterial infusion every 4 weeks. Five patients (26% of 19 evaluable) achieved a partial response for 3 to 10 months and 5 patients presented a stabilization for 2 to 7 months. Toxicity was mild in most patients, with nausea, vomiting and myelosuppression being the most frequent side-effects. No renal or auditory toxicity was observed. One patient developed central nervous toxicity and another one a reversible fall in visual acuity. Finally, carboplatin infused by the intraarterial route seems to be an active drug, less toxic than cisplatin, in malignant gliomas, and further trials are warranted.

[Immediate hematologic tolerance of extended irradiations after chemotherapy. Apropos of 78 cases of Hodgkin's disease stage III and IV without marrow involvement treated at the Gustave-Roussy Institute]. / Tolérance hématologique immédiate des irradiations étendues après chimiothérapie. A propos de 78 cas de maladies de Hodgkin stades III et IV, sans envahissement médullaire, traitées à l'Institut Gustave-Roussy.

Early hematotoxicity following 4 to 8 courses of polychemotherapy has been analysed in 78 patients (mean age 32.5 years) treated for advanced stage Hodgkin's disease (53 stages III, 25 stages IV). Toxicity occurred in a third of the patients, and led to interrupt the treatment in one case out of 7, definitively in half of them. The thrombocyte lineage appeared the most sensitive to irradiation. Toxicity was proportional to the target volume (42% of upper and infra-diaphragmatic field versus 11.5% of one sided irradiation, P = 0.01). Toxicity was more frequent after infra-diaphragmatic irradiation (32% of para-aortic field, 43.75% of inversed Y field) than after mantle field (12.3%, P = 0.01). Tolerance to extended field irradiations seemed better in young patients. Sex, stage, type of chemotherapy did not influence toxicity in our series. Abnormalities of the blood count before irradiation was predictive of toxicity. While expecting development of megakaryocytic growth factors of autologous bone marrow transplantation, we suggest: 1) to achieve total lymphoïd irradiation in three periods (mantle field then lombo-aortic field-/+ spleen, then iliac and inguinal fields); 2) to wait, if possible, until normalization of the hemogram before starting the irradiation.

Class I and II HLA typing after a 10 Gy-4 hour therapeutic total body irradiation.

Class I and II HLA typing was investigated before and at various intervals after a 10 Gy total body irradiation delivered over 4 h, prior to allogeneic bone marrow graft for various hematological malignancies, in 14 patients. A reliable class I HLA typing appeared to be possible in almost all cases 6-8 hours after the start of irradiation but was only possible in 5 patients after 24 h. Preliminary results with class II antigens might suggest a more marked "fragility" of this antigen class after irradiation. These results encourage the drawing of blood samples for HLA grouping as soon as possible after accidental whole-body irradiation.

[Serological study of toxoplasmosis in Vietnam in a population of drug users (Ho Chi Minh city) and pregnant women (Nha Trang)]. / Etude sérologique de la toxoplasmose au Vietnam dans une population de toxicomanes (Ho Chi Minh ville) et de femmes enceintes (Nha Trang).

Toxoplasmosis is a neglected disease in Vietnam particularly in populations with a high risk of developing complications. The seroprevalence of Toxoplasma gondii was calculated by testing blood samples for Toxoplasma specifically immunoglobulin G and immunoglobulin M on 300 intravascular drug users and on 300 pregnant women. Among intravascular drug users, the seroprevalence of IgG and IgM was 7.7% and 0.08%, respectively. In pregnant women the prevalence of anti-toxoplasmosis IgG and IgM was respectively 11.2% and 0%. 0.28% of all estimated pregnancies in Vietnam are affected with toxoplasmosis, i.e. around 4800 pregnancies per year. In conclusion, a screening of Toxoplasma infections should be recommended in HIV/AIDS patients.

[Randomized trial comparing mitoxantrone with adriamycin in advanced breast cancer]. / Essai randomisé comparant la mitoxantrone à l'adriamycine dans les cancers du sein évolués.

Between June, 1983 and December, 1984, 142 patients with metastatic breast cancer were enrolled in this controlled, multicentre trial. The patients were given cyclophosphamide (600 mg/m2) plus 5-fluorouracil (750 mg/m2) and either adriamycin (45 mg/m2) (CAF) or mitoxantrone (13 mg/m2) (CNF). All drugs were administered intravenously on the same day every 21 days. An objective response was obtained in 28 of the 66 assessable patients (42.8%) in the CAF group (with 9 complete responses) and in 30 of the 71 assessable patients (42.2%) in the CNF group (with 6 complete responses). At the moment, the median duration of response is 37+ weeks with CAF and 34+ weeks with CNF (n.s.). It is still too early to evaluate the duration of survival. The major toxicity was bone-marrow suppression which required delayed administration or dose reduction in 40-45% of the patients. Nausea and vomiting were of comparable frequency in both groups, but they appeared to be less severe with CNF. Alopecia was less frequent and less pronounced in the CNF group. Moderate and clinically non-significant reduction of left ventricular ejection fraction was observed at cardiac ultrasonography or scintigraphy in 6 (10%) CAF patients and 2 (3%) CNF patients. None of the patients developed heart failure. Our results show similar response rates and toxicity with CAF and CNF. However, the mitoxantrone-containing treatment had a slight advantage as regards alopecia and the severity of nausea and vomiting.

[Neuro-degenerative diseases: role of reactive oxygen species and of apoptosis]. / Maladies neurodégénératives: rôle des espèces activées de l'oxygène et de l'apoptose.

NEURON DEATH: Major progress in our understanding of the pathophysiology of neurodegenerative diseases has greatly benefited from the convergence between work devoted to reactive oxygen species (including nitric oxide) and programmed cell death, or apoptosis, and exitotoxicity. LATERAL AMYOTROPHIC SCLEROSIS: The discovery of a mutation in the copper-zinc superoxide dismutase gene in patients with lateral amyotrophic sclerosis has made it possible to analyze the events leading to neuron death in transgenic mice. An overload of reactive oxygen species accelerates apoptosis and oxidative stress is implicated in excitotoxicity which is a hyperstimulation of excitatory amino acides (glutamate, aspartate) producing neuron death. OTHER CHRONIC CONDITIONS: Based on evidence from the mouse model, apoptosis, excitotoxicity and oxygenated free radicals could play a causal role in other neurodegenerative diseases including HIV-related encephalopathy, Parkinsonís disease and Alzheimerís disease.

Cerebral arterial disturbances in a transient encephalopathy induced by methotrexate.

The mechanism of the transient encephalopathy induced by high dose systemic administration of methotrexate (HDMTX) is unknown. Metabolic and vascular hypothesis have been formulated but convincing evidence is lacking. We report the first case of vascular disturbances (thinness of cortical arteries on angiography, reversible fall down of cerebral flow and increase of carotid resistance) in a young Algerian patient treated for an osteogenic osteosarcoma. This observation might lead to the exploration by non invasive and easily repeatable techniques of the cerebral vascular dynamic in patients submitted to HDMTX and thus contributed to the elucidation of the mechanism and to the prevention of these neurological side effect.

[Serum potentiation of hemolysis induced in vitro by adriamycin in man]. / Potentialisation par le sérum de l'hémolyse induite in vitro par l'adriamycine, chez l'homme.

Human red cells lysis produced by adriamycin in vitro was investigated both in phosphate medium pH7 and in human serum. Drug induced hemolysis, that appeared with concentrations markedly above plasmatic levels seen in therapeutic, was stongly enhanced by serum. It is the first relations of modulation through a human serum factor of a biological action of adriamycin.