Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid

We report the results of an expanded trial of 5-fluorouracil (FUra) combined with high-dose folinic acid for treatment of patients with advanced colorectal or gastric adenocarcinoma. In each treatment course, the patients received both FUra (340-400 mg/m2/day by iv infusion over 15 minutes) and folinic acid (200 mg/m2/day by iv bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete response (CR) and partial response (PR) rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to FUra attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates above 10(-5) M were achieved after a rapid single iv injection of 200 mg/m2 of folinic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Normal activation of the supplementary motor area in patients with Parkinson''s disease undergoing long-term treatment with levodopa.

Regional cerebral blood flow (rCBF) changes in cortical motor areas were measured during a movement of the dominant right hand in 15 patients with Parkinson's disease deprived of their usual levodopa treatment, in 11 patients with Parkinson's disease undergoing long-term treatment with levodopa, and in 15 normal volunteers. The supplementary motor areas were significantly activated in the normal subjects and in the patients receiving levodopa but not in the patients deprived of levodopa. The contralateral primary sensory motor area was significantly activated in all three groups. The ipsilateral primary sensory motor cortex was not activated in the normal subjects and the non-treated patients but was in the patients treated with levodopa. It is concluded that the supplementary motor area hypoactivation which is observed in akinetic non-treated patients with Parkinson's disease is not present in patients undergoing long-term treatment with levodopa. This result suggests that (a) levodopa improves the functional activity of supplementary motor areas in Parkinson's disease and (b) there is no pharmacological tolerance to this effect. The ipsilateral primary motor cortex activation observed in the patients treated with levodopa could be related to levodopa-induced abnormal involuntary movements.     

Is there any desensitization of presynaptic alpha 2-adrenergic receptors in hypertension? Experimental and clinical studies]

Several authors have discussed an alteration of adrenergic receptivity in arterial hypertension. De Champlain (Hypertension 1990; 8: S77-S85) suggested that postsynaptic alpha 1-adrenergic functions became dominant while beta-adrenergic functions are attenuated in arterial hypertension. However, the status of presynaptic alpha 2-adrenoceptors remains unknown. The present study investigates presynaptic alpha 2-adrenoceptors in hypertension through the measurement of plasma levels of noradrenaline after administration of yohimbine, an alpha 2-adrenoceptor antagonist, in essential hypertension. Yohimbine (0.2 mg/kg per os) induced a 73% increase of plasma levels of noradrenaline in hypertensive patients (n = 12) and a 178% one in normotensive subjects (n = 6, p < 0.05). A similar significant difference was found in experimental neurogenic hypertension observed in awake dogs 3 weeks after sinoaortic denervation: the increase in plasma concentrations of noradrenaline after yohimbine (0.5 mg/kg i.v.) was +279% in hypertensive versus +642% in normotensive dogs (p < 0.05). The results show that the magnitude of the yohimbine-induced sympathetic activation is lower in hypertensives than in normotensives. They suggest the existence of a presynaptic alpha 2-adrenoceptor desensitization in arterial hypertension. The abnormality of this presynaptic inhibitory mechanism can increase the sympathetic tone and help to develop and maintain arterial hypertension.     

Unilateral iris metastasis of cutaneous malignant melanoma]

We describe a case of cutaneous malignant melanoma metastatic to the iris and the angle 31 months after excision of the primary tumor in a 37-year-old caucasian female patient. The patient who had numerous metastases (lung, liver, cerebrum, skin) suffered from secondary glaucoma and died 5 months after the discovery of the intraocular metastases. The glaucoma was treated with medications and cyclocryotherapy. There was no response of the iris metastases to cyclical combined chemotherapy.     

La fonctionnalité alimentaire : illusion aujourd’hui, réalité demain

Foods have always been considered by man as a means of ensuring his physiological needs, allowing the growth, development and preservation of the body and its tissues (nutritional value of food). To this can be added the feelings of satisfaction and well-being that food gives to its consumer, thus constituting an element that is fundamental for our physiological and mental balance (the sensorial value of food).Nevertheless, recent scientific studies have shown that over and above the ensuring of nutritional needs, eating habits can also adjust certain functions of the human organism and thus play a beneficial or harmful role on one's health (the functional value of food).The whole concept of nutrition has been enriched by the notion that eating is not only a survival reflex (satisfaction derived through eating and the avoidance of harmful effects due to eating deficiencies or excesses): eating aims to improve one's health and well-being and to reduce the risk of developing various pathologies. These new data open interesting new horizons in today's context where health is increasingly expensive and people are increasingly concerned to improve their quality of live.     

Autoimmune diseases in myelodysplastic syndrome favors patients survival: A case control study and literature review

Background

We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis.

Generation of potent T(h)1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic-like cells

Dendritic cells (DC) are a group of potent antigen-presenting cells (APC) specialized for initiating T cell immune responses. They originate from the bone marrow and upon stimulation with bacterial products, cytokines or CD40 ligation they acquire the ability to migrate to the secondary lymphoid organs. In vitro DC can be generated from human CD34(+) bone marrow cells and CD14(+) peripheral blood monocytes after culture with different cytokine combinations. Since most leukemic cells and tumors in general are devoid of APC capacities, various strategies have been used to increase their recognition and confer the capacity of antigen presentation on them. Because of our interest in the design of vaccine immunotherapy protocols for the adjuvant treatment of patients with lymphoid malignancies (LM), we chose to explore the capacity of human acute lymphoblastic leukemia, chronic lymphocytic leukemia and plasma cell leukemia to differentiate into cells with APC and DC features. Our results among a sample of 10 patients demonstrate that such approach is feasible. Leukemic cells could be induced in the presence of IL-4 and CD40L to exhibit a DC morphology with a phenotype of mature DC-like cells. They could also induce a potent proliferative response in naive CD4(+) T cells. In addition, they expressed chemokine receptor CCR7 and CD62L, and could drive T cells towards a T(h)1 response with secretion of IFN-gamma. Our strategy leading to increased LM cell immunogenicity may have potential clinical applications and LM appear to be attracting candidates for adjuvant vaccination and adoptive immunotherapy.     

Presence of HLA-D/DR antigens on the membrane of breast tumour cells

HLA-D/DR (Ia) glycoproteins were identified in human breast carcinoma and normal mammary gland cells by means of an anti-Ia monoclonal antibody. Two techniques were used: (1) immunoperoxidase staining performed on histological sections and (2) Ia glycoproteins were isolated as follows: firstly by radioactive labelling of isolated cells, then by filtration on Sephadex G25, followed by Lens culinaris chromatography, and immune complex formation and then elution on protein A-Sepharose. Lastly, the immune complex was studied by chromatofocusing. Both techniques revealed that Ia expression was found in carcinoma cells, but not in normal cells.