[Polyneuropathies in vitamin B1 deficiency in Reunion and Mayotte islands in 70 patients of Maori and Comorian descent]. / Polyneuropathies par hypovitaminose B1 aux îles de la Réunion et de Mayotte: à propos de 70 cas d'origine mahoraise et comorienne.

Beriberi is an uncommon disorder related to thiamine deficiency. It is mainly found in underdeveloped countries among populations with poorly diversified diet, consisting largely of milled white cereals, a poor source of thiamine. In industrialized countries, thiamine deficiency with cardiac failure is more frequently found than the dry beriberi in high risk groups like chronic alcoholics. Nevertheless our attention was drawn to an outbreak of 70 cases of dry beriberi which occurred from 1997 to 2005 in the French territories of Reunion and Mayotte islands. It was characterized by an acute or sub-acute sensorimotor polyneuropathy with axonal lesions, affecting the lower limbs and occasionally the upper limbs, sometimes associated with cardiac beriberi. It affected young, non alcoholic individuals from the Mahoran and Comorian community who were in apparent good health when the illness occurred. Our study highlighted the feeding habits which are partly responsible for the development of the disease due to a chronic lack of thiamine and which probably contributed together with multiple cofactors to trigger off the illness. But many elements and mainly biological ones, also lead us to think that there is a genetic predisposition to develop this neuropathy.

[Fetal version by acupuncture (moxibustion) versus control group]. / Etude comparative de la version foetale par acupuncture (moxibustion) versus groupe témoin.

OBJECTIVE: Breech delivery is known to increase maternal and fetal morbidity. Several methods have been suggested to increase the rate of fetal reverse. The aim of this study was to assess the efficacity of acupuncture or more exactly moxibustion at the 34th AW to increase the rate of fetal reverse. MATERIALS AND METHODS: Clinical trial over 68 major pregnant women, adjusted on parity, whose fetus was in breech presentation at the 8th month. They were randomised to receive or not the treatment. It is the first randomised clinical trial performed on this subject in France, from January 1st 2006 to April 30th 2008. RESULTS: The rate of fetal reverse is not statistically higher with moxibustion for the primipara (7/19 versus 6/19) and for the multipara (9/14 versus 11/19). CONCLUSION: Moxibustion, such as performed in this trial, has not modified the fetal rate reverse either on primipara or on multipara.

Action of peripheral or intrathyroidal lymphocytes on autologous thyrocytes cultured in follicles in collagen gel.

We have studied the action of peripheral blood lymphocytes (PBLs) and intrathyroidal lymphocytes (ITLs) on the biochemical and hormonal metabolism of autologous thyrocytes cultured in follicles in a collagen gel. The production of tumour necrosis factor alpha (TNF-alpha) in culture was also measured. Thyroid tissues and lymphocytes were obtained from ten patients with Graves' disease and from five control subjects. Lymphocyte-induced cytotoxicity was evaluated in autologous thyrocytes cultured in a collagen gel by several tests; neutral red uptake, lactate dehydrogenase activity and glutathione level. Hormonal metabolism was assessed by evaluating tri-iodothyronine (T3) and total cAMP production under TSH stimulation. TNF-alpha levels were measured in supernatants after 5 days of coculture. PBLs altered biochemical metabolism, T3 synthesis and cAMP production in autologous thyroid follicles. These inhibitions were greater than those obtained with ITLs. No difference was seen between cells obtained from patients with Graves' disease and those from normal subjects. TNF-alpha levels secreted by PBLs were higher than those secreted by ITLs. The concentrations of this cytokine decreased in coculture. Significant correlations were observed between the decrease in biochemical and hormonal parameters and TNF-alpha levels. Exogenous TNF-alpha and high doses of interferon gamma inhibited follicle metabolism, especially hormone secretion. In conclusion, thyrocytes cultured in follicles provide a more sensitive model than monolayer cultures for analysis of lymphocyte-induced interactions. Lymphocytes gradually inhibit the biochemical and hormonal metabolism of autologous thyroid follicles depending on the isolation method. These alterations may be particularly attributed to TNF-alpha secreted by lymphocytes. The cytokine-induced inhibition of thyroid hormonal function apparently involves the adenylate cyclase system.

[11C]L-methionine uptake in gliomas.

Treatment of gliomas remains disappointing in spite of a great number of experimental biological data and of randomized therapeutic studies. This could be partly explained by the inefficiency of our conventional methods to assess the regional metabolism of these tumors. The use of positron emission tomography (PET) brings encouraging possibilities in this field. We report our preliminary experience of measuring regional cerebral methionine uptake with PET after intravenous injection of [11C]L-methionine. Twenty-two patients with histologically confirmed gliomas were studied. An ECAT II positron emission tomograph was used for scanning. The position of the plane was chosen to include a major section of the tumor in the reconstructed brain slice. The protocol required a two-step examination: 1) after injection of 15 to 25 mCi of [11C]L-methionine, 12 scans were performed over a period of 46 minutes; and 2) 18 hours later, regional cerebral blood volume was measured in the same slice after intravenous injection of 2 to 4 mCi of 68GaCl3. The tumoral region of interest was determined as being the area of maximum activity. For each patient we calculated the ratio, R, between the activity in this tumor region of interest and the activity in the contralateral healthy symmetric region of interest which was used as an "internal standard" for the same patient. We correlated the ratio R with the histological grading. In 22 patients, mean values of R were calculated for each tumor: Grade II (n = 5): R = 1.04 +/- 0.27; Grade III (n = 5): R = 1.68 +/- 0.22; and Grade IV (n = 12): R = 2.33 +/- 0.86.(ABSTRACT TRUNCATED AT 250 WORDS)

Red blood cell polyamines as biochemical markers of supratentorial malignant gliomas.

Data obtained during post-surgical monitoring (2 to 28 months) of 32 histologically confirmed malignant supratentorial glioma patients, are reported here. It was observed that: whatever the grade of malignancy, 100% of the patients whose tumor recurred showed, on at least one occasion, abnormal red blood cell (RBC) spermidine (SPD) (greater than 14 nmoles/8.10(9) RBC) or spermine (SPM) (less than 2 nmoles/8.10(9) RBC) levels. 30% of the patients whose tumor recurred had abnormal RBC polyamine concentrations, one to six months before any other sign of tumor progression. In patients with normal RBC polyamine values, clinical and tomodensitometric indications of tumor progression have to be reconsidered. During individual follow-up, RBC SPD levels of each patient were generally significantly correlated to those of SPM, and the slopes of their straight regression lines (SRL) appeared to be related to the importance of the intracranial cell proliferation. In such conditions we established the regression equation of the group of all recurring patients taken together. We propose a graphic model, including a space corresponding to RBC SPD and SPM levels observed in case of tumor recurrence, which can be utilized routinely in neuro-oncology during the monitoring of post-operative malignant supratentorial glioma patients.

The antitumoral action of polyamine linked cyclophosphazenes on human malignant glioma heterografts in nu/nu mice.

Since the polyamine metabolism system is very active in proliferative glioma cells, polyamine linked drugs are to be considered as potential antineoplastic agents against malignant gliomas. This study reports the trial of a new compound lineage, the Polyamine Linked Cyclophosphazenes, on human glioblastoma heterografts in nu-nu mice. Two agents are tested: DIAM 3 and DIAM 4. Both show an important antineoplastic action either on a chronic treatment schedule or as single dose. Systemic tolerance is satisfactory.

Inhibition of the growth of U-251 human glioblastoma in nude mice by polyamine deprivation.

An almost complete prevention of tumor growth was achieved in U-251 human glioblastoma xenografted nude mice, by partial decontamination of the gastrointestinal tract and feeding of a polyamine-free diet containing inhibitors of ornithine decarboxylase (DFMO) and of polyamine oxidase (MDL 72527). After one week of polyamine deprivation, spermidine concentrations were lowered, and spermine levels were increased in all tissues. In contrast, putrescine concentrations were only reduced in tumor and in brain. Erythrocyte polyamine determinations revealed differences similar to those observed in tissues: spermidine concentration was lowered by 50% and spermine level was 3-fold increased. If this or related treatments should become of therapeutic importance in the future, then the determination of erythrocyte polyamine levels might be of diagnostic value.

[Long-term immunosuppression in multiple sclerosis: evaluation of treatments begun before 1972]. / Immunosupression au long cours dans la sclérose en plaques: évaluation des traitements commencés avant 1972.

Multiple sclerosis patients have been continuously treated by azathioprine. Only severe progressive forms were selected. The protocol of inclusion and follow-up is detailed. All cases started before 1972 have been reviewed, i.e. 102 cases. Of these 102, 35 stopped azathioprine during the first years and the reasons for this drop-out are analysed. Sixty seven treatments have been maintained for more than 5 years. An evaluation of these 67 patients through the Kurtzke scale shows that the 40 cases with a remittent progressive course have been stabilized as long as they were under treatment. Relapses were observed after discontinuing the therapy. In such cases azathioprine was restarted, leading again to stabilization. Twenty seven cases following a continuous progressive course at the time azathioprine was started showed no evidence of a benefit and kept on worsening. Complications related to treatment (as observed on 240 patients from 1967 to 1982) are detailed with special reference to infections, liver disease and malignancy. Even if the results observed on the course of severe remittent progressive forms of MS are in favor of continuous therapy by azathioprine, this should not be extended to all cases of MS at their first manifestation. It has to be limited to rapidly worsening cases, appreciated after a period of evaluation, when a threatening loss of autonomy may justify some limited risks.

[Cannabis and cannabinoid receptors: from pathophysiology to therapeutic options]. / Cannabis et récepteurs cannabinoïdes: de la physiopathologie aux possibilités thérapeutiques.

BACKGROUND: Although cannabis has been used as a medicine for several centuries, the therapeutic properties of cannabis preparations (essentially haschich and marijuana) make them far most popular as a recreational drugs. STATE OF THE ART: Scientific studies on the effects of cannabis were advanced considerably by the identification in 1964 of cannabinoid D9-tetrahydrocannadinol (THC), recognized as the major active constituent of cannabis. Cloning of the centrally located CB1 receptor in 1990 and the identification of the first endogenous ligand of the CB1 receptor, anandamide, in 1992 further advanced our knowledge. PERSPECTIVE AND CONCLUSIONS: Progress has incited further research on the biochemistry and pharmacology of the cannabinoids in numerous diseases of the central nervous system. In the laboratory animal, cannabinoids have demonstrated potential in motion disorders, demyelinizing disease, epilepsy, and as anti-tumor and neuroprotector agents. Several clinical studies are currently in progress, but therapeutic use of cannabinoids in humans couls be hindered by undesirable effects, particularly psychotropic effects. CB1 receptor antagonists also have interesting therapeutic potential.

[Familial cerebral cavernomas: discovery made during an epileptic seizure in a 10-year-old girl]. / Cavernome cérébral familial: révélation par une épilepsie chez une fille de 10 ans.

The assessment of an epileptic seizure in a 10-year-old girl originating from Reunion Island revealed a case of familial cerebral cavernous angioma. Multiple hemorrhagic lesions seen during a cerebral magnetic resonance imaging (MRI) scan was suggestive of cavernomas. A cerebral MRI scan in the father showed multiple asymptomatic lesions, thus confirming the familial nature. A genetic study carried out on the patient and her father confirmed the presence of a mutation of the KRIT1 gene with an autosomal dominant transmission. In these disorders, an MRI scan in the patient's parents offers great diagnostic advantages. This screening leads to precautionary measures that are easy to put in place.

Polyamines in human brain tumors. A correlative study between tumor, cerebrospinal fluid and red blood cell free polyamine levels.

Polyamine levels have been studied in brain tumor patients. We focused our study on the relationship between tumor, cerebrospinal fluid (CSF) and red blood cell (RBC) polyamine levels. Our results are the following: Polyamine levels in CSF are consistently increased, whatever the histological type may be. The highest tumoral concentrations are found in medulloblastoma. In glioblastomas, the RBC spermidine levels are higher than in the other types of tumors and there is a highly significant correlation between the spermidine/spermine ratio in tumor and RBC. Therefore, RBC polyamine determination might be of clinical interest in the monitoring of patients with glioblastomas.

Unusual combination of Cis platinum and radiotherapy followed by a three fractions per day irradiation in splitcourse: a phase I-II study in brain glioma patients.

An unusual protocol based on a preliminary clinical study on cylindromas metastasized to the lung was proposed to brain glioma patients: Day 2 100 mg/m2 i.v. Cis platinum (Cis PII) followed at days 3 and 5 by 6 Gy irradiation (RT) in two fractions and three days. Five cycles were scheduled at 21 days interval. On disease progression a three fractions per day radiotherapy regimen (3 FRT) in split-course (two series of 22.50 Gy in 15 fractions and five days separated by a two weeks period of rest) was then delivered to the patients. All patients had a measurable mass on the CT scan. 19 were entered into the study: 13 as first line therapy (group A) and six for salvage treatment (group B). Tolerance was globally good. Eight patients were considered responders at the end of five cycles of Cis PII-RT. They were all group A patients. Median symptom-free interval was six months for the whole population. Survival was twelve months. The 3 FRT was well tolerated but does not seem to have improved the therapeutic gain of the chemoradiotherapy combination. The present study concerns patients whose prognosis was poor on inclusion: surgery inadvisable or unsatisfactory and diagnosis mainly based on biopsy only. The number and the duration of responses justify further study into Cis PII as first line therapy as either an effective cytotoxic drug or a potential radio enhancer.

T1 and T2 proton nuclear magnetic resonance (N.M.R.) relaxation times in vitro and human intracranial tumours. Results from 98 patients.

137 samples of intracranial tumours have been studied in proton NMR spectroscopy. T1 and T2 relaxation times are above those of normal grey and white matter. Differential diagnosis between benign and malignant brain tumours does not seem feasible upon proton T1 and T2 alone. Histological correlations allowed us to specify secondary changes accounting for T1 and T2 variations (oedema, microcyst, stroma reaction, necrosis).

NMR investigation of experimental chemical induced brain tumors in rats, potential of a superparamagnetic contrast agent (MD3) to improve diagnosis.

The different steps of development of chemically induced brain tumors were investigated in rats by MRI using a superparamagnetic contrast agent, magnetite-dextran nanoparticles (MD3). Sprague Dawley strain pregnant female rats were injected intravenously with ethylnitrosourea solution at the end of pregnancy. Offspring whelped by the inoculated mother were followed. MRI examinations were performed at 0.5 T. MD3 nanoparticles were injected intravenously at a dose of 5 mg Fe kg(-1) body weight 30 min before rat sacrifice. After sacrifice, histological slices were stained with hematoxylin-eosin. Relaxation times were measured at 40 MHz and 37 degrees C. MD3 nanoparticles act differently according to the step of the tumor development. Before tumor appearance, at a step characterized by the presence of abnormal cell clusters, relaxation time T2 increased significantly. The T2-weighted image showed a small increase in signal intensity in the lesion. Image contrast was improved by MD3 nanoparticles injection because of the decrease in healthy tissue signal intensity. The T1-weighted image did not provide any additional information. In presence of a minute tumor, relaxation times decreased in tumor but increased in surrounding tissue. The T1-weighted image showed a hypersignal on the border of an hyposignal. T2-weighted image showed a hypersignal in the same area. Signal intensity was not modified after MD3 nanoparticles injection. When new vascular capillaries developed in the tumor, MD3 nanoparticles cross into the cerebral parenchyma. Transmission electron microscopy showed magnetite crystals in this specific area on cytoplasm vesicles of glial cells and in tumor-specific membrane arrangements. On T2-weighted image, the hypersignal consisted of a well defined part and a second more fuzzy part, its signal being extinguished after MD3 nanoparticles injection. Necrotic areas and edema can be discriminated. The use of such a superparamagnetic contrast agent would be helpful in early detection of tumor development and in improving distinction of tumor mass from its vascular environment in patients.

Effect of S9788 on the efficiency of doxorubicin in vivo and in vitro in medullary thyroid carcinoma xenograft.

In medullary carcinoma of the thyroid (MTC), drug resistance remains the major obstacle to effective chemotherapy. In this work, we studied the effect of S9788 on doxorubicin (DOX) efficiency in a MTC cell line (TT cells) injected in nude mice. After two passages, TT cells were injected in 40 nude mice divided into four groups [controls and groups receiving DOX alone (10 mg/kg), S9788 alone (50 mg/kg) or both DOX + S9788]. The weight of the mice, tumoral volume (TV), doubling time (DT) of the tumor and survival time of mice were evaluated in each group. In addition, the efficiency of DOX with or without S9788 was assessed by the inhibition of tumoral growth and specific growth delay. In vitro, glycoprotein P 170 (P-gp) was detected on tissular sections and on tumoral cells by immunocytochemistry or flow cytometry with several monoclonal antibodies: JSB1, MRK 16, C219 and UIC2. In vivo the weight of the mice decreased slightly with DOX and dropped dramatically with DOX + S9788. The DT of the tumors increased with DOX over controls (22.5 +/- 8.5/12.7 +/- 3.9 days) and showed a higher value with DOX + S9788 (29.2 +/- 11.4 days). Inhibition of tumoral growth, 89% with DOX, fell to 47.6% with DOX + S9788. Specific growth delay increased with the double treatment (130 versus 75% with DOX alone). In vitro, P-gp was not detected on tissular sections and cells whatever the method and the antibody used. In conclusion, S9788 potentiates the efficiency of DOX treatment in vivo. The absence of P-gp may result from the absence of translation of the MDR1 gene. The reversal effect of S9788 may involve another resistance mechanism such as the MDR Sister of MRP.

Glial tumoral proliferation induces changes in the state and physical properties of water during ENU-induction of brain tumors in rats.

Modifications of water state were analyzed during ethylnitrosourea-induction of brain tumor in rats. Four different steps were identified in the cancerization process according to NMR and histological findings. Two analogies were observed in the pattern of bound' water at decreasing temperatures: first the pattern was similar in tumor area and white matter, second the pattern was similar in the same area of normal brain tissue and cortical gray matter. This phenomenon, which corroborates previous reports on liver cancerization, points out that pathological proliferation of glial cells, and their progressive organization into multiple layers, is accompanied by a transformation of water properties at the cellular level.