[Diabetic muscular necrosis: three Afrocaribbean cases]. / Nécrose musculaire du diabétique : trois cas Afro-caribéens.

INTRODUCTION: Diabetic muscular infarction is an exceptional complication of diabetes mellitus. Patients with macro- and microvascular manifestations are mostly concerned. Muscular pain with swelling of the thigh is the main manifestation, sometimes associated with fever. OBSERVATIONS: We report here five cases of diabetic muscular infarction in three Afro-carribean patients with atypical clinical features. The surgical biopsy procedure allowed the diagnosis and ruled out pyomyositis, a more common bacterial disease on tropical condition. CONCLUSION: This report of three cases of this exceptional disease in a small population seems more related to the high prevalence of diabetes mellitus in the French West Indies than to their ethnic origin.

Tumor stroma-containing 3D spheroid arrays: A tool to study nanoparticle penetration.

Nanoparticle penetration through tumor tissue after extravasation is considered as a key issue for tumor distribution and therapeutic effects. Most tumors possess abundant stroma, a fibrotic tissue composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which acts as a barrier for nanoparticle penetration. There is however a lack of suitable in vitro systems to study the tumor stroma penetration of nanoparticles. In the present study, we developed and thoroughly characterized a 3D co-culture spheroidal array to mimic tumor stroma and investigated the penetration of silica and PLGA nanoparticles in these spheroids. First, we examined human breast tumor patient biopsies to characterize the content and organization of stroma and found a high expression of alpha-smooth muscle actin (α-SMA; 40% positive area) and collagen-1 (50% positive area). Next, we prepared homospheroids of 4T1 mouse breast cancer cells or 3T3 mouse fibroblasts alone as well as heterospheroids combining 3T3 and 4T1 cells in different ratios (1:1 and 5:1) using a microwell array platform. Confocal live imaging revealed that fibroblasts distributed and reorganized within 48h in heterospheroids. Furthermore, immunohistochemical staining and gene expression analysis showed a proportional increase of α-SMA and collagen in heterospheroids with higher fibroblast ratios attaining 35% and 45% positive area at 5:1 (3T3:4T1) ratio, in a good match with the clinical breast tumor stroma. Subsequently, we studied the penetration of high and low negatively charged fluorescent silica nanoparticles (30nm; red and 100 or 70nm; green; zeta potential: -40mV and -20mV) and as well as Cy5-conjugated pegylated PLGA nanoparticles (200nm, -7mV) in both homo- and heterospheroid models. Fluorescent microscopy on spheroid cryosections after incubation with silica nanoparticles showed that 4T1 homospheroids allowed a high penetration of about 75-80% within 24h, with higher penetration in case of the 30nm nanoparticles. In contrast, spheroids with increasing fibroblast amounts significantly inhibited NP penetration. Silica nanoparticles with a less negative zeta potential exhibited lesser penetration compared to highly negative charged nanoparticles. Subsequently, similar experiments were conducted using Cy5-conjugated pegylated PLGA nanoparticles and confocal laser scanning microscopy; an increased nanoparticle penetration was found in 4T1 homospheroids until 48h, but significantly lower penetration in heterospheroids. Furthermore, we also developed human homospheroids (MDA-MB-231 or Panc-1 tumor cells) and heterospheroids (MDA-MB-231/BJ-hTert and Panc-1/pancreatic stellate cells) and performed silica nanoparticle (30 and 100nm) penetration studies. As a result, heterospheroids had significantly a lesser penetration of the nanoparticles compared to homospheroids. In conclusion, our data demonstrate that tumor stroma acts as a strong barrier for nanoparticle penetration. The 30-nm nanoparticles with low zeta potential favor deeper penetration. Furthermore, the herein proposed 3D co-culture platform that mimics the tumor stroma, is ideally suited to systematically investigate the factors influencing the penetration characteristics of newly developed nanomedicines to allow the design of nanoparticles with optimal penetration characteristics.

Review of prostatic surgical procedures at a predominantly black hospital: a 22-year study.

This article reports the results of a pathoepidemiological study of a cohort of black men who had prostatic surgery at Howard University Hospital between 1968 and 1989. The median age of patients at diagnosis of prostate cancer increased by 8 years during the study period, indicating either a delay in seeking medical care or a true delay in onset of the disease. The trends of prevalence of biopsies with cancer in various age groups suggested a sharp rise in the incidence of prostate cancer after the age of 70. The significant increase in popularity of needle biopsy during the period 1982 to 1989 after a 7-year plateau is an indication of increased perceived value of this procedure with experience and technical improvement. The prevalence of biopsies with cancer in all successive time periods of the study showed a bimodal distribution with an early hump in the 50- to 54-year-old age group. This hump is analogous to the break in the rising incidence of breast cancer between the ages of 47 and 52 (Clemmesen hook). This similarity could be explained on the basis of hormonal dependence of the two cancers.

[Treatment of corticodependent systemic lupus erythematosus with low-dose methotrexate]. / Traitement du lupus érythémateux systémique corticodépendant par le méthotrexate à faibles doses.

The authors report an open prospective study in a group of 16 patients who presented systemic lupus erythematosus with cutaneous and articular symptoms, and who required treatment with a minimum dose of 15 mg per day of prednisone. Methotrexate was given at a dose of 7.5 mg IM per week. Efficacy was demonstrated at the third month with a statistical analysis of four evolution parameters. Improvement was observed in 13 patients out of 16 and permitted the reduction of the amount of prednisone required. Secondary relapse occurred in four cases in spite of an increase in the dose of methotrexate (10 mg per week). Minor side effects were observed in four cases, and methotrexate was discontinued in only two cases. This study suggests that treatment by low doses of methotrexate is beneficial to patients with articular and cutaneous manifestations of corticodependent systemic lupus erythematosus and this therapy could be corticosteroid-sparing.

[Sarcoidosis and leukemia/T-cell lymphoma associated with HTLV-1 virus infection in adults (apropos of a case)]. / Sarcoïdose et leucémie/lymphome T de l'adulte associées au virus HTLV-I (à propos d'une observation).

The HTLV-1 virus causes a disturbance of the immune system, the evaluation of which is often difficult. We report a case of sarcoidosis in a 49 year old woman of Martinique as evidenced by bilateral hilar adenopathy, hypercalcaemia, uveitis and granulomatous lesions on histological examination. Serological was positive for HTLV-1 antibodies. Three years later she developed an adult T-cell leukemia/lymphoma. The relationships between the HTLV-1 retroviral infection and different pathologies observed are discussed.

[Systemic lupus erythematosus in Martinique: an epidemiologic study]. / Lupus systémique en Martinique: enquête épidémiologique.

PURPOSE: To review epidemiological and clinical aspects of systemic lupus erythematosus (SLE) in Martinique, French West Indies. METHODS: Cases of SLE were identified by attending physicians. Patients who presented with at least four of the criteria defined by the American College of Rheumatology were included. Determination of incidence and prevalence included the new cases arising during the 1990-1999 period and 1999 population census results. Probability of survival was based on the use of the Kaplan-Meier estimator. RESULTS: Two hundred and eighty-six patients were studied, including 265 females (92.7%). The average annual incidence was 4.7 cases per 100,000 inhabitants (95% confidence interval [CI]: 2.5-6.9). The prevalence for 1999 was 64.2 cases per 100,000 inhabitants (CI: 56.2-72.2). The mean age at onset was 30 years. Eleven percent of all patients had at least one parent with SLE. Renal disease was present in 139 patients (48.6%), and neurological disorders were diagnosed in 70 patients (24.5%). Patients tested positive for the following antibodies: anti-Sm (37.1%), anti-RNP (58.7%), anti-SSA (47.2%). Mean survival time was: 96.4% (CI: 94.1-98.7) at 5 years, 91.8% (CI: 87.9-95.7) at 10 years. Survival was significantly reduced in patients with end-stage renal disease (n = 40, chi 2 = 6.96, P < 0.01). CONCLUSION: The high incidence of SLE in Martinique and the immunological characteristics of patients were found to be similar to those described in other populations of African descent. The frequency of renal disease and survival rates were identical to those reported in Caucasians.

[Hypercalcemia of T-cell leukemia in adults]. / Les hypercalcémies des leucémies à lymphocytes T de l'adulte.

A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells.

The prevalence of overweight and obesity, and distribution of waist circumference, in adults and children in the French Overseas Territories: the PODIUM survey.

AIM: This study aimed to describe the prevalence of overweight (excluding obesity) and obesity, and distribution of waist circumference, in children and adults in four French Overseas Territories (Guadeloupe, Martinique, French Guiana in the Caribbean and French Polynesia in the Pacific Ocean). METHODS: The survey was designed to provide a sample representative of the population in each of the four territories. The protocol aimed to evaluate 600 adults (aged ≥ 15 years) and 300 children (aged: 5-14 years) in each territory. RESULTS: In children, the differences were small among the territories in the prevalence of overweight (excluding obesity), as defined by the International Obesity Task Force (IOTF): Guadeloupe, 15.4%; Martinique, 17.0%; French Guiana, 13.2%; and French Polynesia, 17.2% (P = 0.49). Larger, significant, differences were observed for obesity, with prevalences of 7.2%, 7.7%, 5.4% and 15.9%, respectively (P < 0.002). In adults, the prevalence of obesity also differed significantly among the territories: 22.9%, 22.0%, 17.9% and 33.1% in Guadeloupe, Martinique, French Guiana and French Polynesia, respectively (P < 0.001, adjusted for age and gender). However, overweight (excluding obesity) was again more homogeneously distributed, with prevalences of 31.7%, 33.6%, 30.3% and 34.4%, respectively (P = 0.43, adjusted for age and gender). Waist circumference was larger in French Polynesia than in the other territories in both genders, and in both children and adults. CONCLUSION: While the distribution of overweight was relatively homogeneous, the prevalence of obesity differed considerably across the four territories. It was especially high in French Polynesia, and in children and women. Appropriate programmes are urgently needed in these populations, especially in children, to avoid the morbidity associated with obesity.

Regulatory mechanisms involved in modulating RGS function.

Regulator of G-Protein Signaling (RGS) refers to a conserved 120-125 amino acid motif that was first identified by its ability to negatively regulate G-Protein-Coupled Receptor (GPCR) signalling. Mechanistically, RGSs were found to regulate GPCR responses by binding to and stimulating the GTPase activity of the receptor-activated GTP-bound G alpha subunits. There are now over 25 mammalian RGSs containing proteins that are reported to carry out a variety of functions, many of which are unrelated to GPCR signalling. RGS proteins range in size from small proteins that contain little more than an RGS box to very large proteins that contain a variety of domains. The selectivity of function of the RGS proteins is attributable to the divergence of the RGS sequences as well as the presence of a variety of functional motifs, which allow them to interact with other proteins. Here we focus on the RGSs that are involved in modulating GPCR signalling by reviewing the diversity of the mechanisms involved in regulating these RGSs.

Osteoarticular disorders of haematological origin.

Clinical abnormalities of the musculoskeletal system may be the first manifestation of sickle haemoglobinopathies, leukaemias, lymphomas and haemophilia. In addition to this, known patients with these diseases exhibit a variety of osteoarticular features. The painful crisis is the most common manifestation of sickle cell disorders, but avascular necrosis, osteomyelitis and various forms of arthritides are also common. In haematological malignancies, bone pain and arthritis may occur at any stage of the disease. The diagnosis must be confirmed by the presence of malignant cells on histological examination of various samples. Haemarthrosis is the main symptom of haemophilia. It needs early treatment to avoid damage to the joints. The availability of new safe coagulation factors has improved the prognosis of haemophilia.

[Atypical lumbar and nerve-root pain associated with the HTLV-1 virus]. / Lomboradiculalgies atypiques associées au virus HTLV-1.

The human retrovirus HTLV-1 (Human T-cell Lymphotrophic Virus) is responsible for malignant proliferations of mature T lymphocytes. It is also now implicated in neurological disorders dominated by spastic paraplegia. A study of 140 cases of lumbar and root pain enabled us to identify 8 of apparently idiopathic atypical lumbar and root pain which led to the discovery of a positive HTLV-1 serology performed routinely. These cases were remarkable in terms of the rarity and minimal extent of spinal cord signs and of Lasegue's sign, their duration of more than a year and the existence of neurological signs indicative of central involvement. In 2 patients there was secondary progression to a spastic paraparesis. It would appear that the neurotropism of HTLV-1 virus is not limited to the central nervous system but that it can also involve the peripheral nervous system as indicated by certain cases in the literature as well as those collected in Martinique, an endemic area for the virus. Rheumatologists should be aware of this possibility when confronted with such cases of atypical lumbar and root pain and should seek the existence of an HTLV-1 virus infection among other viral etiologies, in particular when the patient concerned comes from an endemic area.

Polyarthritis in HTLV-1-infected patients. A review of 17 cases.

A retrospective study was conducted in Martinique to identify patients with polyarthritis and positive serologic tests for the human T-cell lymphotropic virus Type I (HTLV-1). Patients with metabolic or bacterial causes of polyarthritis were excluded. We found 17 cases of HTLV-1-positive polyarthritis (6.7% of the total of polyarthritis patients followed in our department); there were 14 females and three males, and all the patients were West-Indian blacks. Mean age at diagnosis was 50 years. Five patients also had tropical spastic paraparesis. The polyarthritis was the inaugural manifestation of T-cell leukemia in one patient. Four patients had received blood transfusions. Fever, myalgia, and/or skin lesions were present at onset of the polyarthritis in seven cases. All 17 patients had peripheral, bilateral, symmetric polyarthritis; the most commonly involved sites were the hands (17/17) and knees (14/17). Three patients had rheumatoid factor and five had antinuclear antibody. Ten patients met at least four American Rheumatism Association criteria for rheumatoid arthritis; they accounted for 6.7% (10/150) of all polyarthritis patients managed in the same hospital department during the same period. We compared these ten patients with 20 HTLV-1-negative rheumatoid arthritis patients matched on gender, ethnic origin, and disease duration. There were no significant differences between the two groups for any of the parameters studied.