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Background: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization., Objectives: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France., Methods: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations., Results: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results., Conclusion: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19-70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14-24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm (range, 4-294); mean CD8: 236/mm (range, 1-1293); mean CD19: 113/mm (range, 3-547); and mean NK cell count: 122/mm (range, 5-416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm and NK cell count <100/mm were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.

Objectives: Human immunodeficiency virus (HIV) infection and protease inhibitor (PI)-based antiretroviral treatment might increase large artery (aortic) stiffness compared with healthy untreated controls. To clarify the role of PI therapy in the progression of subclinical arteriosclerosis in patients with HIV, we investigated the impact of PI treatment on arterial stiffness., Methods and Results: In our single-centre, cross-sectional study, normotensive male HIV patients free from overt cardiovascular disease received PI treatment (n=60) or no PI treatment (n=42). The PI group had a significantly higher pulse wave velocity (PWV) than the PI-free group (9.0 ± 1.4 vs. 8.1 ± 1.3m/s; P=0.016). There was a significant positive correlation between age and PWV in the PI-free group (R(2) 0.310; P<0.0001) and, to a lesser extent, in the PI group (R(2) 0.181; P<0.0001). PI treatment was associated with a significant increase in the adjusted slope of the curve relating age to PWV as compared with no PI treatment., Conclusions: In normotensive HIV patients, PI treatment significantly increases both aortic stiffness and the positive correlation between PWV and age. Aortic stiffness predicts cardiovascular mortality, thus these results provide new insight on the relationship between PI treatment, mechanical arteriosclerotic and cardiovascular risk., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Glutamic acid decarboxylase antibodies (GAD-abs) are an immunological factor involved in type 1 diabetes and other diseases involving the central nervous system. This report is of a patient with type 1 diabetes and a rare case of non-paraneoplastic limbic encephalitis mediated by anti-GAD65 antibodies that improved with the use of immunosuppressive drugs., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Sunitinib inhibits numerous tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastatic invasion. It is indicated in case of metastatic renal carcinomas and gastrointestinal stromal tumors (GIST) resistant to imatinib. Prospective and retrospective studies have shown association between use of sunitinib and hypothyroidism affecting more than 50% of patients in some series. More amazing, was the non-visualisation of thyroid tissue evaluated with thyroid ultrasonography in two cases. Mechanisms of this side effect are not elucidated. Some studies have suggested destructive thyroiditis but no evidence of autoimmunity has been demonstrated. Anti angiogenic effect could be another hypothesis. Recently antithyroperoxidase activity of sunitinib has been demonstrated. Because hypothyroidism is easily accessible to treatment, screening of thyroid abnormalities is mandatory every three months to improve quality of life of these patients. This unique thyroid side effect of sunitinib with the non-visualisation of thyroid suggests a possible and promising antitumor activity in thyroid cancer.

Hypothalamic-pituitary (HP) sarcoidosis has 2 main endocrine manifestations: diabetes insipidus and hyperprolactinemia. We conducted the current study to investigate pituitary dysfunction and perform imaging of the HP area in patients both immediately following diagnosis and after treatment. The study included 6 men and 3 women, with a mean age of 30 years at the onset of sarcoidosis. All patients had both hormonal and magnetic resonance imaging (MRI) HP disorders. All patients had anterior pituitary dysfunction, 7 of them with associated diabetes insipidus. Nine patients had gonadotropin deficiency and 3 had hyperprolactinemia. MRI revealed infundibulum involvement in 5 patients, pituitary stalk thickness abnormality in 5, and involvement of the pituitary gland in 2, associated with other parenchymal brain or spinal cord lesions in 6 patients. All patients had multiple localizations of sarcoidosis, and 5 had histologically confirmed sinonasal localizations. Mean follow-up of the HP disorder was 7.5 years. All patients received prednisone. There was no correlation between the number of hormonal dysfunctions and the area of the HP axis involved as assessed by MRI. Although corticoid treatment was associated with a reduction of radiologic lesions, only 2 patients had partial recovery of hormonal deficiency. In conclusion, hormonal deficiencies associated with HP sarcoidosis frequently include hypogonadism (all patients) and to a lesser degree diabetes insipidus (7 of 9 patients). MRI abnormalities improved or disappeared in 7 cases under corticosteroid treatment, but most endocrine defects were irreversible despite regression of the granulomatous process. Most cases presented with multivisceral localizations and an abnormally high proportion of sinonasal localizations.

Introduction: Churg-Strauss syndrome (CSS) is a systemic disease characterized by asthma, blood and tissue eosinophilia, and necrotizing vasculitis with extravascular eosinophilic granulomas., Cases: We describe two cases of patients with CSS: a 56-year-old man, whose presentation was highly unusual because its initial predominant manifestation was odynophagia, and a 35-year-old man whose disease was diagnosed after a work-up because of nausea, vomiting and abdominal pain. In both cases, thoracic computerized tomography scans showed congestive esophagitis with a markedly thickened esophageal wall at diagnosis and at relapse. Both the vasculitis and the esophageal involvement improved with treatment., Discussion: Gastrointestinal (GI) involvement is frequent in CSS patients and is one of the major causes of death associated with CSS. Nonetheless, eosinophilic vasculitis-related esophagitis is very rare.

Plasma cell granuloma (PCG) is a rare, benign inflammatory tumor composed of myofibroblasts, abundant plasma cells, and lymphocytes combined with collagen. A thyroid localization of PCG is extremely rare, and surgical therapy is indicated. We report the case of a 35-yr-old woman with a thyroid PCG, associated with Hashimoto's thyroiditis, that was responsible for tracheal compression. Surgery was performed, but the thyroid could not be removed because of the fibrotic process. The patient was treated with corticosteroids and immunosuppressive therapy. Dyspnea and dysphagia improved within 1 month, whereas thyroid volume returned to normal within 3 yr. We also review other reports of thyroid PCG in the literature and discuss the differential diagnosis and treatment. Although the use of immunosuppressive therapy has never been reported for thyroid PCG until now, this treatment may represent a good alternative to surgery in life-threatening, unresectable PCG.

Introduction: The frequent etiology of panhypopituitarism is a hypopituitary adenoma. An exceptional cause, with less than 40 cases in the literature, is intra-sellar carotid aneurism., Observation: A 55 year-old woman was treated for panhypopituitarism related to bilateral aneurism of the carotid arteries. Hormone exploration revealed anterior pituitary deficiency involving all the axes except the corticotrophin and prolactin functions. Pituitary MRI showed an atrophic pituitary, compressed by two calcified aneurismal formations located on the terminals of two internal, partially thrombotic, carotid arteries. Surgical treatment was not envisaged 12 years later. Replacement therapy for life was initiated., Comments: The mechanisms explaining the occurrence of panhypopituitarism secondary to intra-cranial aneurism are hypothetical: compressive phenomena, ischemia and apoplexy of a pituitary adenoma related to the aneurism.

Background: Medullary thyroid carcinoma is a rare tumour derived from the thyroid parafollicular calcitonin-secreting cells. Calcitonin is a very specific marker of this cancer that allows preoperative diagnosis. Serum calcitonin assay is particularly useful to define the postoperative state of patients (cured, apparently cured, not cured) and, because of its great sensitivity, it has a major place in the postoperative follow-up., Objective: To identify, among patients thyroidectomized for medullary thyroid carcinoma (MTC), the characteristics of authentic recurrent MTC [re-elevation of stimulated serum calcitonin (CT) level measured by a sensitive immunoradiometric assay, after postoperative normalization]., Patients and Methods: We first collected, through the national registry of the French Calcitonin Tumour Study Group (GETC), patients who had undergone a total thyroidectomy with or without lymph node surgery and who were not cured at the last follow-up visit. Among 453 such patients included in the database, 15 patients met the criteria for authentic recurrence as defined in previous studies: they had been first considered as cured during the 6 months following the initial surgical procedure (basal and pentagastrin-stimulated serum calcitonin level

Dilated cardiomyopathy may be primary or secondary. Although some causes are well known, such as toxic substances (alcohol, chemotherapy...) or viral infections, biochemical abnormalities are much less common. The authors report the case of a 58 year old woman with no previous history admitted to hospital for an inaugural episode of cardiac failure. The ECG showed sinus tachycardia with a long QT interval (560 mm) and a dilated hypokinetic cardiomyopathy with a left ventricular ejection fraction of 20%. The aetiological investigation showed severe hypocalcaemia (0.66 mmol/L) related to primary hypoparathyroidism. This is an important cause to remember because its treatment leads to correction of the cardiac disease, usually within weeks.

The control of hypertension in diabetic hypertensive patients prevents micro and macroangiopathy complications. Our prospective study was designed to evaluate the level of treatment of hypertension in type II diabetic patients at the time of referral to our endocrinology unit and after a mean follow-up of 9.2 months. Five hundred and sixty four patients (sex ratio: 1.15, mean age of 56 +/- 13, mean BMI of 28 +/- 15, mean duration of diabetes of 11.3 +/- 9.9) were referred to our unit. Among these, 42% had an antihypertensive drug (58% under monotherapy, 42% under combinations) and 92% had a documented history of CHD. Glycemic and blood pressure controls were stable during follow-up. HbA1c remained unchanged (8.95% at admission, 8.8% at 9 months) BP decreased from 143/84 +/- 26/13 mmHg to 142/82 +/- 23/13 mmHg. Fifty six percent reached a BP goal of 140/90 mmHg whereas 42% achieved a BP goal of 130/85 mmHg at 9 months compared to respectively 56% and 39% at admission. A multivariate logistic regression analysis showed that initial value of SBP (p < 0.0001), age (p < 0.0001), BMI (p = 0.006), HbA1c (p = 0.018) were independent factors of non control of hypertension. In conclusion, follow-up of hypertension diabetic patients would be focussed on identified and modifiable factors.

Idiopathic CD4+ lymphocytopenia (ICL) is a rare syndrome affecting adults and defined by a stable loss of CD4+ T cells in the absence of any known cause of immune deficiency. Defective T-cell proliferations to mitogens and antigens have been described in some of such patients displaying clinical signs of immune deficiency such as opportunistic infections. We investigated here the hypothesis that T-cell depletion and dysfunction could be due to biochemical defects of the CD3-TCR pathway in CD4+ and/or CD8+ subsets from three patients with severe stable ICL (below 150 CD4+ T cells/microliter) and opportunistic infections. Patient 1 had a general T lymphocytopenia, whereas patients 2 and 3 displayed a selective loss of CD4+ T cells. We observed in all patients a major reduction of the proliferative response to CD3-TCR stimulation that affected only the depleted T-cell subpopulation. Moreover, in two cases, impaired early biochemical events of the CD3-TCR pathway were detected. In patient 1 and 3, we found a defect (of distinct intensity) of CD3-induced protein tyrosine phosphorylation in CD4+ cells compared to control cells, whereas this process was normally induced in CD4+ T cells from patient 2. Taken together, this study reveals that the heterogeneity of the ICL syndrome was situated at the cellular level, and involved in two cases abnormalities of transducing molecules of the CD3-TCR pathway.

During recent decades, undeniable progress has been made with regard to the management of arterial hypertension. Larger numbers of patients are aware they have hypertension, receive treatment and benefit from this therapy. Furthermore, significant reductions have been observed in morbidity and mortality resulting from cardiovascular diseases. The objectives of hypertension treatment have been formulated on the basis of results of extensive epidemiological studies. Only a few patients receiving monotherapy actually achieve and maintain acceptable blood pressure levels. The complex pathogenesis of essential hypertension, the implications of nervous and humoral counter-regulatory effects, the heterogeneous character of individual responses to any given class of antihypertensive treatment and the onset of adverse effects all account for these failures. The search for a simple, effective and well-tolerated treatment based on a low dose combination of 2 classes of antihypertensive agents is consequently legitimate. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg enables patients to benefit from the antihypertensive synergy of a beta-blocker and a calcium antagonist (dihydropyridine). Several open-ended or double-blind, controlled studies have shown that this combination produces a more marked antihypertensive effect than the individual components used alone or other reference monotherapies. Furthermore, it has been shown that this effect persists throughout the entire 24-hour period; this has been confirmed by 24-hour blood pressure monitoring. Short and medium term tolerability is significantly improved: the side effects commonly associated with the 2 drugs when used alone are reduced with the combination formulation since the 2 active substances have different and complementary mechanisms of action. In addition, long term studies have shown that therapeutic efficacy and tolerability remain stable and have even been seen to improve over a 12-month period. The fixed combination of atenolol-nifedipine has a role in strategies for the treatment of mild to moderate hypertension, particularly under the following conditions: when first-line monotherapy has failed to attain specific clearly defined objectives, including stabilised blood pressure levels together with acceptable tolerability. when patient compliance is jeopardised as a result of undesirable side effects. when the vascular burden is aggravated through lack of attention to individual risk factors in hypertensive patients. In more serious forms of hypertension, the atenolol-nifedipine combination can replace sequential monotherapies or other combination treatments that have failed to comply with the various criteria of therapeutic efficacy. Controlling arterial hypertension commonly requires polytherapy with 3 or even 4 different drugs in conjunction with particularly strict rules governing hygiene and diet. The addition of the fixed combination of atenolol-nifedipine simplifies the treatment of patients with arterial hypertension by limiting the daily doses and reducing laboratory monitoring.

Identification of a responder to an antihypertensive treatment is helpful and also very difficult in an open uncontrolled study. The existence of many arbitrary methods to define a responder, the placebo effect and the regression to the mean phenomenon coexist and give spurious interpretation. We analysed an open study recruiting 6,530 hypertensive patients (DBP > or = 95 mmHg at entry), treated with the same antihypertensive drug during 3 months. Mean initial and at 3 months blood pressures were respectively 178/101 mmHg and 151/86 mmHg. We observed significant variation in the % of responders (20 to 80%) to a drug when applying different methods. Placebo effect and regression to the mean lead to an overestimation. Without a placebo controlled design, we suggest to increase the BP level for inclusion to determine the % of responders with the standard goal pressure (DBP < 90 mmHg) and to use Oldham's method for adjusting for the regression to the mean unless the coefficient of correlation found is around zero and if upper level of DBP is not selected for inclusion.

Objective: Intravenous pentamidine induces hypo- and hyperglycaemia (dose-dependent toxicity on islet beta cells), pancreatitis and nephrotoxicity. Conversely, aerosolized pentamidine (AP) is usually devoid of systemic side-effects: few reports of hypo- or hyperglycaemia have been published. Our study aimed to assess the influence on glucose homeostasis and insulin secretion of long-term exposure to AP used for prophylaxis of Pneumocystis carinii pneumonia in HIV-positive patients, and to compare the impact on insulin secretion of AP, whether administered for the first time or after prolonged monthly exposure., Design: Retrospective cross-sectional controlled study (main objective) and non-randomized prospective controlled study., Patients: We compared glucose homeostasis and C peptide response to 1 mg intravenous glucagon in patients who had previously inhaled > or = 10 prophylactic aerosols (group 1, n = 21) and in HIV-positive controls (groups 2 and 3, n = 28) who had received none. Both groups were comparable for age and body-mass index, but CD4 T-lymphocyte counts and Karnofsky scores were both significantly higher in the control group., Results: Fasting (T0) blood glucose, fructosamine and response to the first glucagon test were similar in both groups, but postprandial glucose, glycated haemoglobin and fasting C peptide were significantly higher (P < 0.05) in the pentamidine group. A second glucagon test was performed on the same day, 3 h (T3) after AP inhalation in 35 patients (in 21 after > or = 10 aerosols, group 1; in 14 after the first, group 2) and in 14 HIV-positive controls (group 3). The only significant difference between the three groups in C peptide response to this second test was a lower peak T3/peak T0 ratio in group 1. Plasma amylase and creatinine were not altered by the aerosol., Conclusion: Long-term prophylactic exposure to AP had minor but significant effects on glucose homeostasis and insulin secretion but did not modify pancreatic and renal function. The detrimental effects induced by long-term exposure to AP found in our study are probably not clinically relevant, but a more prolonged exposure to AP might conceivably induce more severe alterations.

The treatment of hypertension must fall within a strategy of the early and strict control of blood pressure levels. Only actual normalisation of blood pressure can offer long term benefit regarding the incidence of cardiovascular morbidity and mortality. While major studies undertaken up to now have already proven the benefit of treatment using classical drugs as monotherapy, it is now necessary to offer all young hypertension patients, even mild, with strict control of levels, a non-pharmacological action on risk factors, and a choice of treatments ensuring no loss of part of the prognostic benefit as a result of persistence or worsening or sub-clinical metabolic disorders. It seems logical, when first-line monotherapy is selected from among the five major drug groups recommended, is neither perfectly effective nor perfectly tolerated, and risks worsening a metabolic disorder in the long term, to use a combination of hypotensive drugs. This should enable blood pressure control in 80 to 90% of cases, and improved acceptability, a major factor in treatment compliance. It is reasonable to hope, in the long term, that the use of a combination of lower doses than as monotherapy, will ensure less interference with major metabolic, endocrine and vascular functions, leading to a further improvement in the prognosis of treated hypertension.

The polymerase chain reaction (PCR) was used to detect hepatitis D (HD) viremia in patients infected with the human immunodeficiency virus (HIV). Nineteen (9%) of 206 such patients, unselected for liver disease or HBV infection, were found prospectively to be infected by HDV. Thirty-one anti-HIV-positive patients were studied by means of PCR, and the results were analyzed according to HDV and hepatitis B virus (HBV) serological status. HDV-PCR was positive in 5 patients. Two had detectable serum HDV antigen. Four patients had anti-HD IgM and IgG antibodies. All these patients were HBs antigen-positive, and 3 were HBV-DNA-positive. All the other patients were HDV-PCR-negative. Statistical analysis suggested more extensive liver damage and immunological impairment in HDV-PCR-positive patients. In this unselected HIV-infected population, HDV-RNA detection by PCR was restricted to HDV infected patients in whom 5/19 were positive. This test permitted direct diagnosis of HDV viremia and will be useful for monitoring HDV infection.

We used the polymerase chain reaction (PCR) to detect hepatitis D (HD) viremia in patients infected with the human immunodeficiency virus (HIV). Nineteen (9%) of 206 such patients were prospectively found to be infected by HDV. Thirty-one anti-HIV-positive patients were studied by means of PCR and the results were analysed according to HDV and hepatitis B virus (HBV) serological status. HDV-PCR was positive in five patients. Two had detectable serum HDV antigen. Four patients had anti-HD IgM and IgG antibodies. All these patients were HBs antigen-positive, and three were HBV-DNA positive. All the other patients were HDV-PCR-negative. Statistical analysis suggested more extensive liver damage and immunological impairement in HDV-PCR positive patients. In this unselected HIV-infected population, HDV-RNA detection by PCR was only evidenced in HDV infected patients in whom 5/19 were positive. This test allowed direct diagnosis of HDV viremia and will be useful for the monitoring of HDV infection.

The authors report the case of a patient who received intramuscular injections of bismuth and penicilline for three consecutive years. Twenty-five years later, a lymphoma of the right buttock developed. The tumor was treated with radiotherapy and remained localized for two years. It then diffused to lungs, maxilla and skin. The occurrence of a lymphoma in muscles is thought to be exceptionnal. It has been suggested that lymphomas may develop at the site of silicone injections or of protracted infections. Fibrosarcomas have been reported after intramuscular injections of iron. The observations may suggest that the muscular lymphoma observed in our patient may have been related to the injections of bismuth performed twenty-five years earlier.

An unusual of bilateral adrenal benign adenoma with Cushing's syndrome is reported. Nine months after bilateral adrenalectomy, no more sign of hyperadrenocorticism was present. An adenoma was found in each gland with adjacent tissue atrophic. Physiopathology is not clear even if suppression test by dexamethasone and stimulation test by lysin-vasopressin are compatible with a central origin.

The authors report the cases of 13 patients with parathyroid adenomas and hyperparathyroidism. They estimate that this disease may be observed in about 70/100,000 patients hospitalised in a non-specialised medical department. In four of these patients, the disease was asymptomatic while only four patients presented with symptomatic renal stones. In five patients, immuno reactive parathyroid hormone levels were within normal limits. In contrast, nephrogenic cyclic AMP, measured in 11 patients, was found to be increased in the totality of these patients and could not be decreased by the administration of calcium. An ultrasonographic examination of the neck, performed in 11 patients, showed the adenomas in 6 patients; in three other patients they were located in the neck but measured less than 1 cm in their greater diameter and in other two patients the adenomas were located in the thymus.

Three cases of CMV infection in normal adults are described. The clinical course was benign but with a long period of fever (average 4 weeks), hepatic and immunologic abnormalities (hemolytic anaemia, thrombocytopenia, monoclonal gammopathy). The clinical and biological features of CMV infection in these patients are compared with those of other recently reported series.

The authors report a case of colitis, with anatomo-clinical confrontation, during a treatment with flucytosine. In this fatal colitis, there were neither ulcerations nor pseudo-membranes. The histological data, with significant cytonuclear lesions, were consistent with a toxic-induced disorder of protein synthesis.

Respiratory disorders in homozygous drepanocytosis and double SC heterozygosis are mainly dependent on two factors : repeated infections with, more particularly, pneumococcus or mycoplasma, and epidoses of occlusion of the pulmonary circulation. Mutual reinforcement of these two factors occurs, in so far as the relative hypoxia of an infected lung increases the risk of falciform and thrombosis formation in the pulmonary arterioles. The particular physical and chemical properties of the drepanocyte red cell, and the anaemia, themselves lead to parallel disturbances in pulmonary circulation function and gas exchanges. Possible development of respiratory insufficiency is generally, therefore, the result of chronic pulmonary arterial hypertension. However, the results of respiratory function tests are often fairly analogous to those observed in moderate interstitial fibrosis : reduction in vital capacity, alveolo-capillary block, reduction in CO diffusion space, a shunt effect, and diminished pulmonary compliance. This problem is discussed in relation to findings of diffuse interstitial fibrosis in a 34-year-old man with double SC heterozygosis, who had numerous episodes of bone, abdominal, and pulmonary microinfarcts. The presence of a diffuse interstitial pulmonary fibrosis, evoked by radiological criteria and respiratory function tests and confirmed by transbronchial biopsy, no other aetiology being established, raises the question of the possible genesis of the fibrosis from repeated episodes of microvascular occlusion. Many factors may therefore be involved in the formation of fibrosis of this type, not only the pulmonary artery obstruction from the microthrombi but also the macrophagic perivascular inflammatory response related to the presence of foci of infarction and precipitation of pathological intravascular material.

Polyarteritis nodosa (PAN), with a fatal outcome, developed during the course of a therapeutically controlled Graves'disease. A review of the published literature confirms that two mechanisms may be involved in the onset of PAN in hyperthyroid patients: an immune response, which is probable in the case reported, or a toxic effect related to the treatment of the hyperthyroidism. This case also emphasizes the therapeutical difficulties encountered, in spite of the corticoid and cyclophosphamide associated treatment with plasmapheresis.

Report of the case of a patient, store-keeper at the Roissy airport, suffering from an autochtonous primo-invasion falciparum malaria. The clinical symptoms were hectic fever and painful hepatomegalia, followed 14 days after by a typical tertian fever. All investigations being negative, a laparoscopy was carried out, which showed a black liver, and a biopsy demonstrated the malaria pigment in Küpffer cells. Malaria was confirmed by the study of a blood smear. This diagnostic hypothesis had not been raised, because of the absence of any epidemiologic argument. It seems necessary to think of autochthonous malaria among the etiologies of prolonged summer fevers in people living or working in the neighbourhood of airports, the more so that the frequency of this peculiar mode of contamination should logically increase.

202 cases of Grave's disease were reviewed; among the 81 patients submitted to medical treatment, 53,1 p. 100 of patients failed to respond; 10 p. 100 relapsed and 35,9 p. 100 are euthyroid. The factors favouring a treatment failure were: age below thirty, severity of thyrotoxicosis, big enlargement of thyroid gland, duration of treatment shorter than 12 months. Relapses are more frequent after two years of medical treatment. Subtotal thyroidectomy was performed in 82 patients: 9,5 p. 100 relapsed, permanent hypothyroidism developed in 30,5 p. 100 and 50 p. 100 were euthyroid. The factors favouring post-operative hypothyroidism are estimated weight of the thyroid remnant, the moderate size of goiter and perhaps a six to twelve months preoperative medical treatment. 39 patients had I 131 therapy: among them, 24 p. 100 relapsed, 25,7 p. 100 had permanent hypothyroidism and 50,3 p. 100 are euthyroid.