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Background: Protein glycosylation is an important post-translational modification shown to be altered in all tumour types studied to date. Mucin glycoproteins have been established as important carriers of O-linked glycans but other glycoproteins exhibiting altered glycosylation repertoires have yet to be identified but offer potential as biomarkers for metastatic cancer., Methodology: In this study a glycoproteomic approach was used to identify glycoproteins exhibiting alterations in glycosylation in colorectal cancer and to evaluate the changes in O-linked glycosylation in the context of the p53 and KRAS (codon 12/13) mutation status. Affinity purification with the carbohydrate binding protein from Helix pomatia agglutinin (HPA) was coupled to 2-dimensional gel electrophoresis with mass spectrometry to enable the identification of low abundance O-linked glycoproteins from human colorectal cancer specimens., Results: Aberrant O-linked glycosylation was observed to be an early event that occurred irrespective of the p53 and KRAS status and correlating with metastatic colorectal cancer. Affinity purification using the lectin HPA followed by proteomic analysis revealed annexin 4, annexin 5 and CLCA1 to be increased in the metastatic colorectal cancer specimens. The results were validated using a further independent set of specimens and this showed a significant association between the staining score for annexin 4 and HPA and the time to metastasis; independently (annexin A4: Chi square 11.45, P = 0.0007; HPA: Chi square 9.065, P = 0.0026) and in combination (annexin 4 and HPA combined: Chi square 13.47; P = 0.0002)., Conclusion: Glycoproteins showing changes in O-linked glycosylation in metastatic colorectal cancer have been identified. The glycosylation changes were independent of p53 and KRAS status. These proteins offer potential for further exploration as biomarkers and potential targets for metastatic colorectal cancer.

Background: In Guadeloupe and Martinique, two French Overseas Departments, colorectal cancer (CRC) has become an essential public health issue. However, little is known about CRC characteristics and the p53 status in these populations, particularly in Guadeloupe, whereas certification of a cancer registry has been recently validated., Methods: This was a descriptive retrospective study of 201 patients who, between 1995 and 2000, underwent surgery for CRC in the Guadeloupe Teaching Hospital (GlpeTH; 83 patients) and in the Martinique Teaching Hospital (MqueTH; 118 patients). The clinicopathological features and the p53 expression, evaluated with immunohistochemistry, were compared at the time of diagnosis. A relationship between these parameters and the p53 expression was also studied. Data were analysed, using the SPSS computer software version 17.0., Results: No statistical difference was found between the two groups of patients regarding age (p = 0.60), percentage of young patients (≤50 years; p = 0.94)), sex (p = 0.47), histological type (p = 0.073) and tumour sites (p = 0.65), although the GlpeTH patients were diagnosed with more distal colon cancers (54.2%) than the Mque TH patients (47.4%). By contrast, a significant difference was found regarding the tumour grade (p < 0.0001), the pTNM stage (p = 0.045) and the pT stage (p < 0.0001). Regarding p53 expression, solely for the MqueTH patients, nuclear expression was associated with pTNM, the percentage of p53 negative tumours increasing with the progression of the pTNM stages (p = 0.029)., Conclusions: For the first time, this study reveals discrepancies in clinicopathological features and in the p53 status between the two groups of patients. The GlpeTH patients were diagnosed with more moderated CRCs but with few CRCs at pTNM IV stage. By contrast, the MqueTH patients were diagnosed with more differentiated tumours, but with many more CRCs at pTNM IV stage. This paradox may be due to differences in tumour location (distal vs proximal), multiplicity of the genetic profiles of patients, or patients getting treatment elsewhere. Although our study is limited due to its small size, it emphasizes the originality of our results.

Using a transdisciplinary methodological approach we have conducted a multifactorial analysis in Martinique and Guadeloupe in order to elucidate the aetiology of prostate cancer. In 2002, world age standardized rates of prostate cancer were 152 new cases per 100,000 person-years in the two islands; one of the highest worldwide rates and much higher than those reported for other Caribbean islands and metropolitan France. Using a linear regression analysis, we found that the growth curves of incidence rates for Martinique and metropolitan France have been significantly diverging since 1983. That these curves are not parallel suggests that although a Caribbean genetic susceptibility factor may be involved in carcinogenesis, this factor cannot per se account for the observed growing incidence. On the basis of mapping analysis of soil pollution, we further showed that water contamination by pesticides originates from banana plantations. Moreover, we have established retrospectively that general population subjects investigated in 1972 in Martinique for the presence of organochlorinated pesticides in their adipose tissue had been contaminated by extremely high levels of DDT, DDE, alpha, beta and gammaHCH, aldrin and dieldrin. Our study leads to the conclusion that the growing incidence of prostate cancer cannot be related either to a modification of ethnographic factors nor to a change in lifestyle and therefore suggests that environmental factors such as the intensive and prolonged exposure to carcinogenic, mutagenic and reproductive toxin pesticides may cause prostate cancer.

Background: Colorectal cancer is the second leading cause of cancer death in Western countries, with an incidence progressively increasing in developing countries. Worldwide, colorectal cancer is the second and third leading cause of death by cancer in females and males respectively. According to the Martinique Cancer Register data, colorectal cancer is the second leading cause of death by cancer in women, and the fourth in men. Colorectal cancer exhibits a variable distribution worldwide. This study was conducted to observe variations in colorectal incidence and mortality rates observed over a twenty-year period. Such data will be useful for monitoring changing trends related to onset of an organized screening program., Method: Patients with colorectal cancer diagnosed from 1981 to 2000 in Martinique were included in this study. Data are obtained from the Martinique Cancer Register., Results: The incidence of colorectal cancer in Martinique (16/100,000 and 17/100,000 in the female and male population respectively in the year 2000) is intermediary compared with other countries worlwide. There is a current trend towards increased incidence and mortality. The incidence has increased for cancers localized in the proximal colon, the sigmoid colon and the rectum., Conclusion: The increasing incidence of colorectal cancer in all localisations raises concern in Martinique. A significant predominance of colorectal cancer incidence among the male population in Martinique was not observed. Gender and age do not appear to imply any preferential localisation of colorectal cancer.

Over a period of 2 months, a 60-year-old man, a chicken breeder, experienced low back pain, lower limb weakness predominant on the right side, and urinary difficulties, leading progressively to a flaccid paraplegia with sphincter impairment. Concomitant poor cognitive performances were noted. MRI showed enlargement of the conus terminalis, with a low-intensity signal on T1-weighted images, high-intensity signal on T2-weighted images, and areas of intramedullar contrast enhancement. A biopsy of the lesion showed macrophages containing yeast cells, with PAS and Grocott staining aspects compatible with the presence of Histoplasma capsulatum (Hc). A brain MRI showed multiple localizations in the brain stem and in both hemispheres with associated edema. Disseminated histoplasmosis was confirmed by a biopsy of a sub-maxillary ganglion demonstrating a necrotic tuberculoid lymphadenitis containing yeast cells resembling Hc. Immune tests disclosed the presence of HTLV1 anti-bodies without immunodeficiency nor HIV co-infection. An anti-micotic treatment was started 2 weeks after surgery, with intra-venous amphotericin B, for 21 days, followed by itraconazole, orally for 90 days. Cognitive functions improved significantly in 5 weeks while paraplegia and sphincter impairment remained unchanged. Seven months later, cerebral MR aspects dramatically improved while the conus medullaris lesion diminished, and the edematous component disappeared in all areas. Even though histoplasmosis is endemic in our region, CNS localization is rare, generally in disseminated forms associated with immunodeficiency. Brain granulomas are well-known, but spinal cord histoplasmomas are exceptional: only four cases have been evaluated by MRI. Unlike our case, spinal cord forms generally improve, due to surgery associated with antifungus medication, or sometimes due to specific medical treatment alone but with sufficient dosage.

Background: Exophiala jeanselmei is a dematiaceous fungus that may cause invasive diseases, particularly among immunocompromised hosts. Most reports mention cutaneous or subcutaneous lesions, but no case of nail involvement due to this fungus has been reported until now., Case Report: A 60-year-old man presented with hyperkeratosis and black coloration of the nails of the two thumbs and the two big toes of 4 years' duration. He was a renal transplant recipient and had been treated with prednisone and azathioprine. E. jeanselmei was present on direct examination, then isolated in cultures on repeated samplings from all pathologic nails. He was cured after 6 months of treatment with itraconazole., Commentary: We describe the first case of nail infection due to E. jeanselmei. Itraconazole, which provides a broad spectrum of action on fungal species and achieves high levels of active substance in many tissues, including the nails, appeared to be efficient upon such a nail localization of E. jeanselmei., (Copyright 2002 S. Karger AG, Basel)

Background: Drug-induced panniculitis are uncommon. We report the second case of panniculitis induced by MINE chemotherapy., Case Report: A 31-year-old woman with relapsed Hodgkin disease was treated with MINE cytostatic regimen. Multiple erythematous and painful nodules of panniculitis developed on her chest, abdomen and thighs fifteen days after the beginning of drug administration with a second flare up after second administration of the same drugs. The eruption cleared slowly after treatment withdrawal., Discussion: To our knowledge, our case is the second reported case of panniculitis induced by MINE chemotherapy. Drug-induced panniculitis is uncommon and usually induced by steroid treatment. Some cases of panniculitis induced by atenolol, potassium bromide, apomorphine, interferon alpha and interleukin 2 have been described. Few cutaneous adverse effects are reported with MINE chemotherapy: rash, erythema and swelling of extremities. A case of inflammatory swelling of thighs with hemorrhagic panniculitis due to this treatment has been described recently.

A pilot cervix cancer screening is organized in Martinique since 1991, as part of the programmes of the Fonds National de Prévention d'Education et d'Information Sanitaire of CNAMTS. Evaluation of the programme is conducted by the cancer registry, which includes the measurement of the impact, quality of the Pap smear test, quality of action and efficiency of the programme. Evaluation is a key part that allows to manage the screening programme. According to the results of the organized screening in Martinique, modalities of the evaluation will be discussed with respect to the pilot programme organization, involvement of participants, indicators to collect and the organism in charge of the evaluation.

Human T cell leukemia virus type I (HTLV-I) sequences were sought in labial salivary glands of patients with HTLV-I-associated myelopathy or tropical spastic paraparesis and of seropositive neurologically healthy carriers. HTLV-I proviral DNA was found by polymerase chain reaction amplification in DNA extracted from lip biopsies of every patient. Viral RNA was found by in situ hybridization in the acini epithelium, as well as in lymphocytic infiltrates. This observation suggests that HTLV-I expression in labial salivary glands could participate in the inflammatory lesions observed in these patients. Some seronegative patients with Sjögren's syndrome or dryness syndrome were also positive for viral transactivator tax DNA (41% in Martinique and 16% in non-HTLV-I-endemic region). Despite histologic signs of lymphocytic infiltration, no viral expression was found in the labial salivary glands of these patients.

We report a case of epidermal (or epidermoid) cyst, in a 36-year-old man which developed in the third ventricle. Clinical manifestations were headaches and memory disturbances. On CT scan the tumor occupied the entire third ventricle but was mainly developed on the left side. On CT reconstructed images, the floor of the third ventricle was clearly visible. Using a trans-ventricular approach, the tumor, closely related to the left part of hypothalamus, was totally removed. Later on, because of persistent hydrocephalus, a ventricular shunt was inserted. An aseptic meningitis occurred and resolved spontaneously. The patient exhibited a postoperative transitory Korsakoff's syndrome. Postoperative endocrine investigations showed hypopituitarism. Some intra-ventricular epidermal cysts have been reported, especially involving the fourth ventricle. Their development into the third ventricle is unusual, and in early reports their precise origin appears doubtful. Although they have no characteristic radiological features, the location of epidermal cysts is clearly defined by the CT scan and especially MRI. It would be possible to totally remove epidermal cysts of the third ventricle, avoiding the risk of recurrence.

The epidemiology of melanoma in populations of African-European descent has rarely been reported. The authors studied melanoma in the French West Indies (Martinique), where black Caribbeans and whites represented 96% and 4% of the population, respectively. Among the 85 cases of melanoma collected from 1976 to 1995, blacks represented 75% and whites, 25%. The average incidence rates were 1.48 and 0.9 per 100,000 per year in females and males, respectively. The sole of the foot represented 72% of the primary sites in blacks. Breslow's tumor thickness was > 1.5 mm in 68% of the cases. The 5-year survival was 44%.

Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum of clinical manifestation including adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-I-associated myelopathy (TSP/HAM). In most cases, however, infected patients remain asymptomatic. The participation of the immune system in the pathogenesis of TSP/HAM has been suggested. In this study the IgG antibody response of HTLV-I-infected individuals has been investigated using both ELISA with a panel of nuclear and cytoplasmic proteins and peptides known to be recognized by antibodies from patients with various systemic autoimmune diseases, and immunoprecipitation of ribonucleoproteins from HeLa cell extracts. The results were compared with the reactivity of sera from individuals with non-HTLV-I-related neurological diseases and healthy blood donors. Raised levels of autoantibodies reacting with several nuclear and cytoplasmic antigens were found in TSP/HAM and ATL patients. In asymptomatic HTLV-I-seropositive individuals, both the prevalence and level of IgG antibodies were lower and directed only against a restricted set of antigens. The mechanism of induction of these antibodies still remains obscure. However, the results show that a significant autoimmune response exists in these patients and it may contribute to the pathogenesis of the disease.

We searched for the presence of human T-cell leukemia virus type I (HTLV-I) sequences in central nervous system and muscle lesions of 3 patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and 3 patients with HTLV-I-associated polymyositis. Proviral DNA coding for the Tax protein was found by polymerase chain reaction amplification in DNA extracted from lesions of every patient with TSP/HAM or HTLV-I-associated polymyositis. In contrast, viral RNA was found occasionally by in situ hybridization in muscle lesions of some patients with polymyositis, but was never found in central nervous system lesions of TSP/HAM patients.

The authors report a case of intradural posterolateral spinal arachnoid cyst diagnosed by Magnetic Resonance Imaging (MRI) in a 59-year-old woman. Ten years before, she started to suffer from burning sensation of the left lower limb aggravated by head movements. Physical examination was normal except a sensory dissociation below T10. A myelography was considered as normal. Three years later, motor disturbances occur with progressive weakness. Examination showed asymmetrical spastic paraparesis with a right predominance. On MRI, the spinal cord was displaced at T6-T7 level by a posterior intradural mass with a similar signal than CSF; furthermore, at this level, there was an intramedullary hyposignal on T1 weighted sections. The diagnosis of spinal intradural arachnoid cyst was confirmed at surgery. Microscopic examination of the cyst wall showed fibrous tissue with mild lymphocytic infiltration. Rapid recovery of legs weakness followed, but abnormalities of spinothalamic functions persisted. The clinical characteristics and the MRI data are discussed. The authors conclude that this arachnoid cyst had an inflammatory origin.

Effects of cardiac hypertrophy on coronary capillary density and volume have been studied in two models: systemic hypertension (1c. 2K Goldblatt model, n = 27), and volume overload (aorto-caval fistula, n = 27) compared to a control group (n = 27). Studies have been performed at 1 month, 3 and 6 months. Subendocardial and subepicardial coronary capillaries have been visualized by in injection of fluorescein-labeled dextran (FITC). The body weights were not significantly different in the three groups. The heart weight was the same in hypertensive model and fistula. Goldblatt model was associated with a high blood pressure and an increase in left ventricular wall thickness, whereas fistula was associated with a lower blood pressure and no difference in wall thickness as compared to controls. No difference in subepicardial capillary density was found in the three groups, whereas the subendocardial capillary density was decreased in the two models of cardiac hypertrophy (-25%). Capillary area and mean perimeter, were increased in fistula, due to vasodilatation, and decreased in Goldblatt model in relation to vasoconstriction.