[Anorexia nervosa: Abnormalities in hematological and biochemical parameters]. / Anorexie mentale : anomalies des paramètres hématologiques et biochimiques.

Abnormalities of hematological and biochemical parameters are various and frequent during anorexia nervosa, and are mainly related to malnutrition, weight loss, and compensatory purgative behaviors. They are most often moderate and reversible through appropriate nutritional and weight rehabilitation, as well as well-conducted symptomatic treatment. Severe abnormalities are rarer, but are potentially serious or even fatal. Isolated moderate anemia and leukopenia are frequently noted, with thrombocytopenia being less frequent. Severe, bi-cytopenic, pancytopenic, and spinal cord injury are less common. They can be explained by the gelatinous transformation of the bone marrow caused by malnutrition. Biochemical abnormalities are typically hydroelectrolytic disorders (hypokalemia, hyponatremia, metabolic alkalosis), acute or chronic renal failure, elevated transaminases, risk of potentially severe hypoglycemia, and elevated lipid parameters. During the refeeding syndrome, hypophosphatemia is characteristic and may be associated with hypomagnesemia and hypocalcemia, and thiamine deficiency. Malnutrition can also lead to alterations in hormone status, including hypothyroidism, hypercorticism and hypogonadism, which may be involved in the development of serious bone conditions such as osteoporosis. These abnormalities should be routinely investigated, monitored, and corrected during anorexia nervosa. Early and multidisciplinary management of this eating disorder is essential to prevent chronicity of the disorder and the potential severity of these abnormalities.

Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients.

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters. METHODS: Fasting plasma PCSK9 levels were measured by ELISA in morbidly obese patients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium). RESULTS: A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss. CONCLUSION: RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study.

BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d'étude des Tumeurs Endocrines.

CONTEXT: Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only described by case reports. OBJECTIVE: To improve the knowledge of MEN1 natural history before 21 years old. METHODS: Obtain a description of the first symptoms occurring before 21 years old (clinical symptoms, biological or imaging abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs) occurring in a group of 160 patients extracted from the "Groupe d'étude des Tumeurs Endocrines" MEN1 cohort. RESULTS: The first symptoms were related to hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%), nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%), and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22 cases (14%) and before 5 years old in five cases (3%). Surgery was performed before age 21 in 66 patients (41%) with a total of 74 operations: pituitary adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%), NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET. One patient died before age 21 due to a thymic-NET. Overall, lesions were malignant in four cases. CONCLUSIONS: Various MEN1 lesions occurred frequently before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors may develop at any age. Hyperparathyroidism was the most frequently encountered lesion but was not always the first biological or clinical abnormality to appear during the course of MEN1.

GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a pleiotropic enzyme that is overexpressed in apoptosis and in several human chronic pathologies. Here, we report that the protein accumulates in mitochondria during apoptosis, and induces the pro-apoptotic mitochondrial membrane permeabilization, a decisive event of the intrinsic pathway of apoptosis. GAPDH was localized by immunogold labeling and identified by matrix-assisted laser desorption/ionization-time of flight and nano liquid chromatography mass spectroscopy/mass spectroscopy in the mitochondrion of various tissues and origins. In isolated mitochondria, GAPDH can be imported and interact with the voltage-dependent anion channel (VDAC1), but not the adenine nucleotide translocase (ANT). The protein mediates a cyclosporin A-inhibitable permeability transition, characterized by a loss of the inner transmembrane potential, matrix swelling, permeabilization of the inner mitochondrial membrane and the release of two pro-apoptotic proteins, cytochrome c and apoptosis-inducing factor (AIF). This novel function of GAPDH might have implications for the understanding of mitochondrial biology, oncogenesis and apoptosis.

Clinical and laboratory findings of cytomegalovirus infection in 115 hospitalized non-immunocompromised adults.

We report a retrospective study of 115 hospitalized non-immunocompromised adults with proved or presumed diagnosis of cytomegalovirus infection. Clinical symptoms were fever (95%), constitutive symptoms (80%), joint and muscle pain (41%), shivering (32%), abdominal pain (26%), non-productive cough (20%), cutaneous eruption (20%), and diarrhea (10%). Examination found hepatomegaly (25%), splenomegaly (23%), cutaneous rash (20%), adenopathy (19%), pharyngitis (9%), jaundice (3%) or signs of meningeal irritation (1%). Seventeen patients had a gastrointestinal form (hepatitis, jaundice, colitis, antral gastritis or cholecystitis), eight had a pattern of hemopathy, two interstitial pneumonitis, two pericarditis, two immune thrombocytopenic purpura, two a polymyalgia rheumatica-like pattern, one thrombotic thrombocytopenic purpura, one cutaneous vasculitis and one meningoencephalitis. Sixty-four percent of the patients had atypical lymphocytosis. Hepatocellular injury occurred in 90% of the patients. Nineteen of the patients had biological immune abnormalities. Cytomegalovirus infection should be mainly suspected in any patient with persistent fever, isolated or associated with signs of poor specificity, or in some patients with visceral manifestations of initially unknown origin.

[Cutaneous pyoderma gangrenosum with hepatosplenic localization and monoclonal gammapathy. A case report]. / Pyoderma gangrenosum cutané avec localisation hépatosplénique et dysglobulinémie monoclonale.

Pyoderma gangrenosum is an ulcerative disease of the skin. The histopathological lesions are nonspecific, characterized by a diffuse neutrophilic infiltrate in the dermis. Pyoderma gangrenosum is associated with inflammatory, digestive or articular disease, or acute or chronic hemotology disorders in 50% of the cases, more rarely with monoclonal gammapathy. A visceral localization of pyoderma gangrenosum is rare, simulating a systemic disease or an underlying neoplasia. We report a case of cutaneous pyoderma gangrenosum with splenic and hepatic localizatios associated with an IgG monoclonal gammapathy. We emphasize the efficacy of immunosuppressor treatment and the importance of long-term monitoring of these patients.

[Upper extremity deep venous thrombosis. 40 hospitalized patients]. / Thromboses veineuses profondes des membres supérieurs: à propos de 40 patients hospitalisés.

Deep venous thrombosis is 50 times less frequent in upper than in lower limbs. Data remain poor in the literature. Forty consecutive patients (24 males, 16 females, mean age: 54.5 years) were retrospectively analysed from 161 subjects who underwent venous explorations of the upper extremity for a 3.5 year period in the same center. Diagnosis of thrombosis was made by duplex ultrasonography (n =37) or phlebography (n =3). Main clinical manifestations were edema (n =36) and pain (n =29). Location of thrombosis was humeral (n =1), axillary (n =2), or sub-clavian (n =37, 2 bilateral). The majority of thrombosis (n =29) were secondary to cancer and venous catheter (n =19, 15 implanted ports), to central catheter alone (n =3) or cancer alone (n =7). The 11 others were associated with thoracic outlet syndrome (n =6) or apparent primary thrombosis (n =5). Thrombophilia was identified in 6 out of these 11. During follow up [mean of 9 months (0,5-36)], two patients developed pulmonary embolism, 14 a post-thrombotic syndrome and 16 patients died. Initial therapy included heparin (n =36) or fibrinolysis (n =4). Upper extremity deep venous thrombosis are mostly associated with cancers and venous catheters. Thrombophilia is frequent in the other cases. Heparin followed by oral anticoagulation is the optimal therapy whose duration depends upon underlying condition. Fibrinolysis has not been useful for preventing post-thrombotic syndrome in our study.

[Hematologic and immunologic manifestations of primary cytomegalovirus infections in non-immunocompromised hospitalized adults]. / Manifestations hématologiques et immunologiques de la primo-infection à cytomégalovirus chez l'adulte hospitalisé non immunodéprimé.

PURPOSE: Cytomegalovirus (CMV) infection in non-immunocompromised adults can sometimes induce hematological and immunological disorders that may mislead diagnosis. METHODS: Case reports of hospitalized non-immunocompromised adults with positive serology for CMV including the presence of immunoglobulin M or seroconversion were assessed in a retrospective study (1981-1998). We focused on clinical and biological abnormalities showing the role of CMV in disruption of functioning of hematological and immunological systems. RESULTS: Among 115 patients, lymphoma-like syndrome with large adenopathies and/or splenomegaly was diagnosed in eight patients, uncovering underlying CMV infection. Lymphoma was accompanied by hematoma in two patients. Three patients presented leg purpura (with thrombotic thrombocytopenic purpura in one case), one patient had cutaneous vasculitis and on other a Still's disease. Blood abnormalities were mononucleosis (64%), anemia (20%), and thrombopenia (25%) often of peripheral or hemolytic origin or due to hypersplenia. Electrophoresis of serum proteins showed an increase in immune globulins in 56% of the cases and monoclonal abnormality in nine cases. Immunological assessment was conducted in 18 patients. At least one abnormality was depicted in ten patients, consisting of either antinuclear, anti-platelet or anti smooth muscle antibodies, cryoglobulinemia, rheumatoid factor, or reduced complement fixation. CONCLUSION: Testing for CMV infection can be of value in case of blood or immunological disorders associated with clinical or biological signs. Although hematological disorders occur early, they are rarely severe. Immunological disorders are rarely symptomatic, but often raise issues regarding the potential genesis of immune diseases in at-risk patients.

[Schnitzler syndrome: a rare cause of systemic urticaria]. / Syndrome de Schnitzler: une cause rare d'urticaire systémique.

INTRODUCTION: The Schnitzler's syndrome first described in 1972, associates urticaria, bone pain, and monoclonal IgM gammapathy. EXEGESIS: A 50-year-old man presented symptoms of urticaria restricted to the trunk and lower members, with episodes of fever accompanied by inflammatory pain in the knees and legs. Slight deterioration of his general condition was also observed. Biological findings showed the existence of an inflammatory syndrome. Electrophoresis and immunoelectrophoresis provided evidence for the existence of underlying IgM gammapathy. Bone X-ray demonstrated the presence of tibial and peroneal metaphysis thickening, with hyperfixation on bone scintigraphy. The patient's condition improved after cortisone and colchicine treatment, allowing decrease in coricosteroid doses. Two years later, except for urticaria, clinical features have disappeared and no hematological disorder has been observed.

[Hemorrhagic complications of antivitamin K. Report of 75 hospitalized patients]. / Complications hémorragiques des antivitaminiques K. A propos de 75 patients hospitalisés.

Hemorrhagic complications are the most frequent complications of antivitamin K (AVK) treatments and can be life-threatening. We report 75 patients from a University Hospital. They were 40 males and 35 females (median age 74 years, 20-94), and were classified into 3 grades according to clinical picture: grade 1 (no surgery or transfusion, grade 2: surgery or blood transfusion needed, grade 3: death). 43 patients had grade 1 complications, 27 grade 2, and 5 grade 3 complications. The most frequent complications were muscular hematomas (36 patients), sub-cutaneous hematomas (14 patients), digestive bleeding (13 patients), hematuria (12 subjects). Eight patients had intracerebral bleeding, of whom 3 died. The treatment time was very variable (1 to 988 weeks). Only half patients had a prothrombin rate (PR) below 20% but two thirds had an INR above 5. This study showed that PR was a poor predictor of hemorrhagic complications. INR was a better parameter. For 15 patients, we considered that the indication was unadapted or questionable, among whom 2 died. This work suggests that the promotion of AVK prescription rules should go on.

[Information and education interventions on hygiene levels of a population in which trachoma exists in a hyperendemic and serious form]. / Interventions informatives et éducatives sur les mesures d'hygiène au sein d'une population dans laquelle sévit le trachome sous forme hyperendémique et grave.

The aim of this work is to develop information and education methods in order to obtain better hygienic conditions in Tissint Zaouia (Moroccan province of Ouarzazate). 41% of the population is affected by trachoma with a rate of 18% of active trachoma, 1.6% of the population has a blindness of corneal origin. Topical treatment and surgery of trichiasis must be associated to a better hygiene of the community. Until now mothers and families have not fully perceived the connection between flies and insufficiency of narsing and trachoma transmission. Our specific goals are the following: A--information of target population, B--better understanding of hygiene by mothers and families, C--incitation to face-washing of children, D--perfect identification of trachoma signs by health workers, E--official integration of this program by local authority, F--evaluation of trachoma incidence.

Concurrent herpes simplex type 1 necrotizing encephalitis, cytomegalovirus ventriculoencephalitis and cerebral lymphoma in an AIDS patient.

Unlike cytomegalovirus (CMV) ventriculoencephalitis, herpes simplex virus type 1 necrotizing encephalitis has only rarely been observed in AIDS patients. A 40-year-old bisexual man was followed for an HIV1 infection from 1987 onwards. In June 1993 he was referred for sudden confusion, left hemiparesia and fever. The blood contained less than 10 CD4 lymphocytes/mm3. The patient remained comatose and febrile, and died 4 weeks later. In coronal sections of the brain there was necrosis of the internal parts of the left temporal lobe, necrosis of certain areas of the ventricular walls and a small tumor at the top of the right frontal lobe, which proved to be a polymorphic high-grade lymphoma. CMV ventriculoencephalitis lesions were prominent in the ventricular walls of the occipital lobes and there was a strong nuclear signal for CMV using in situ hybridization. Herpes simplex virus type 1 was shown in the nuclei and cytoplasm of certain neurons and astrocytes in the borders of the necrotized temporal lobe areas by immunohistochemistry, in situ hybridization and electron microscopy, whereas in situ hybridization and immunohistochemistry for CMV were negative in such areas. Necrotizing type 1 encephalitis must not be overlooked in immunodeficient patients.