A rare cancer: cancers of the small intestine. 25 cases diagnosed at the Institut Pasteur de Madagascar from 1992 to 2001

A retrospective survey of cases of cancer of the small intestine observed in the Institut Pasteur de Madagascar (IPM), in the Centre Hospitalier de Soavinandriana (CenHoSoa) and in the Centre Hospitalier Universitaire d'Antananarivo/H?pital Joseph Ravoahangy Andrianavalona (CHUA/HJRA), has been undertaken with the goal to find out epidemiological and diagnostical particularities, as well as the therapeutic measures and their results. Only 25 cases have been found in 10 years (from 1992 to 2001). They represent 5.4% of the digestive cancers diagnosed by the Institut Pasteur de Madagascar. They concern 14 women and 11 men with a mean age of 36 years old at the time of diagnosis. The motive of hospitalization was an acute abdomen (peritonitis, perforation, occlusive syndrome, K?nig's syndrome) in 64.3%, and a chronic abdominal pain often associated with abdominal mass in 35.7%. The duodenum is the predilection seat of the small bowel cancers (50%), followed by the ileum (25%) and the jejunum (10%). A diffuse shape has been observed in 15% of the cases. The most frequent histological type is the lymphoma (40%) followed by the adenocarcinoma (32%).     

A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1

We investigated a French family with a new type of autosomal dominant spinocerebellar ataxia that was excluded from all previously identified genes and loci. The patients exhibited a slowly progressive gait and limb ataxia variably associated with akinesia, rigidity, tremor, and hyporeflexia. A mild cognitive impairment also was observed in some cases. We performed a genomewide search and found significant evidence for linkage to chromosome 7p21.3-p15.1. Analysis of key recombinants and haplotype reconstruction traced this novel spinocerebellar ataxia locus to a 24cM interval flanked by D7S2464 and D7S516.     

Large Scale Manufacturing of B43(Anti-CD19)-Genistein for Clinical Trials in Leukemia and Lymphoma

We have conjugated the murine monoclonal anti-CD 19 antibody B43 to the tyrosine kinase inhibitor genistein to construct an effective immunoconjugate against CD 19 antigen positive hematologic malignancies. The scaled-up production and purification of B43 antibody, genistein, and B43-Genistein immunoconjugate permitted the manufacturing of a highly purified clinical-grade B43-Genistein preparation. In clonogenic assays, B43-Genistein elicited selective and potent cytotoxicity against CD 19 antigen positive human leukemia cells. To our knowledge, this work represents the first effort of producing a clinical-grade genistein immunoconjugate for treatment of B-lineage leukemia and lymphoma.     

Kinetics of paraquat and copper reactions with nitroxides: the effects of nitroxides on the aerobic and anoxic toxicity of paraquat

The toxicity of paraquat (PQ2+) is attributed to intracellularly formed PQ*+, O(2)*-, H(2)O(2), and secondary.OH radicals generated through Fenton-like reactions. Yet, no antidote for PQ2+ toxicity in human has been found also due to poor cell permeability of many common antioxidants that remove toxic species predominantly extracellularly. Cell-permeable nitroxides, which scavenge xenobiotic-derived deleterious radicals and detoxify redox-active metal ions, would be expected to ameliorate PQ2+ toxicity. We have studied using pulse radiolysis the kinetics of the reactions of 2,2,6,6-tetramethyl-piperidinoxyl (TPO) and 4-OH-TPO with PQ*+ and CuIIL(2) (L = 1,10-phenanthroline, 2,2'-bipyridyl) in the absence and presence of DNA. We found that the rate constant for the reaction of PQ*+ with the nitroxides is about 4 orders of magnitude lower than that with O(2). In addition, the rate of the reaction of the nitroxides with CuIL(2) decreases as [DNA] increases, which suggests that nitroxides react significantly slower with bound metal ions. These results explain the failure of 4-OH-TPO to protect bacterial and mammalian cells from PQ2+ toxicity under air. In contrast, the rate of the reaction of PQ*+ with CuIIL(2) was unaffected by DNA. Furthermore, copper toxicity has been attributed mainly to CuI and was observed predominantly for cells subjected to anoxic conditions. It implied that nitroxides would be effective protectants if PQ2+ induces toxicity also under anoxia. Surprisingly, we found that PQ2+ toxicity under anoxia was even greater than that under air, and under these conditions 4-OH-TPO protected the cells from PQ. These results indicate that the mechanism underlying the anoxic toxicity of PQ2+ differs from that operating in the presence of oxygen, and that reduced transition metal ions are most probably the species responsible for PQ2+ anoxic toxicity.     

Results of cranial vault reshaping

This study was designed to assess the outcome of cranial vault reshaping for correction of deformity of the skull and the upper face. A retrospective review of all children who underwent cranial vault reshaping by a single team of surgeons between 1993 and 1996 was performed. There were 10 children in the series. The age at surgery ranged from 6 to 62 months (mean age, 25 months). Five children in the series had untreated sagittal craniosynostosis with scaphocephaly, two had pansynostosis resulting in cloverleaf skull deformity, and three had turricephaly after shunt treatment of hydrocephalus. There was no operative mortality. Blood loss ranged from 250 to 1,500 ml (mean, 422 ml). All patients needed transfusion. There were two major complications resulting from increased intracranial pressure, but both patients recovered completely with no neurological sequelae. Titanium plates and screws were used in all patients, but were removed in two when they became palpable. The 5 children with sagittal craniosynostosis had a normal head shape. The 2 children with cloverleaf skull have improved head shape with persistent increased bitemporal width and round faces. The 3 children with turricephaly after shunting have marked improvement with mild persistent deformity. This study shows that cranial vault reshaping is safe and can lead to a long-term normal head shape in children with late correction of sagittal craniosynostosis. Children with more severe anomalies, particularly syndromic patients, can be improved but will have persistent mild deformity.     

Transient hypoproteinemia and hypoprothrombinemia in an infant

A 7 months old infant with transient hypoproteinemia and hypoprothrombinemia is described. The hypoproteinemia is attributed to protein losing enteropathy, and transient Menetrier's disease is suggested as a possible cause for the protein loss. Assuming that this baby was not vitamin K deficient, and knowing that the molecular weight of prothrombin is lower than that of albumin, the hypoprothrombinemia might be due to prothrombin loss into the gut together with albumin.