[The right to die and assisted suicide: Review and critical analysis]. / Droit à mourir et suicide assisté : état des lieux et analyse critique.

OBJECTIVES: In the context of the present re-examination of the French bioethical laws by the National Advisory Ethics Committee ("Comité consultatif national d'éthique": CCNE), a recent survey indicated a request of the public opinion to obtain a medical aid in end of life and a so-called "assisted suicide". This led psychiatrists to re-consider their role and deontological position which usually led them to consider a request for an assistance in suicide as - a priori - a pathological demand, occurring within a suicidal crisis. The present article intends to: 1) describe the laws and practices of countries which allow medically assisted end of life help procedures; 2) clarify the definitions of "assisted suicide", "assistance to suicide" and "euthanasia"; 3) consider available epidemiological data and the roles given to doctors and, more specifically psychiatrists, in these procedures; 4) analyse the rationale behind these demands. These considerations should enable French psychiatrists to clarify their position when facing requests for a medical aid in dying. METHODS: Four European countries (Switzerland, the Netherlands, Belgium, Luxemburg) and Oregon (the first US state to introduce legislation) were considered, since they accumulated and published a large amount of experiences and data about "assisted suicide" and medical help in dying. In total, 127 articles were selected, mainly from PubMed and Cairn databases, published between 1997 and 2020. These articles deal with legal considerations, epidemiological data, ethical and sociological considerations. RESULTS: Laws and practices differ notably according to the state/country. In Belgium, the Netherlands and Luxemburg, as in Oregon, the medical help in dying has been de-criminalized, as long as certain legal criteria are met. In Switzerland, where no specific law exists in the penal code, non-governmental associations have benefited from the legal vacuum and organized the practice of "assisted suicide" for "altruistic motives". In the scientific and legal literature, the terms used to describe and define the medical help in dying upon request differ greatly. In France, the National Advisory Ethics Committee defines euthanasia ("euthanasie"), assisted suicide ("suicide assisté") and suicide assistance ("assistance au suicide"). Available epidemiological data, whatever the country considered, indicate that requests for a medical aid in dying are expressed mainly by patients aged over 60 years and suffering from cancer. Psychiatric diseases account for only 1% to 3%. Most often, systematic assessment by a psychiatrist is neither requested nor made, when the demand does not occur during a primary psychiatric illness. In the case of an existing primary psychiatric pathology, a psychiatrist assesses the case against formal legal predefined criteria. This latter practice was only recently introduced, after some feedback and after legal actions had been brought to Court. When the underlying motivations of the request are considered, it appears that, even in the absence of an evolving psychiatric condition, several psychological or psychopathological reasons prevail such as spirituality, attachment style, social isolation, despair, depression… which should greatly benefit psychiatric exploration, investigation and expertise. CONCLUSION: In some countries, the request for medically assisted help in dying has become a legal and social reality. In France, where the public debate is still open, it should be emphasized that a psychiatric assessment and interview should be systematically provided to any person requesting medical assistance to die or commit suicide. It is the commitment of psychiatrists to understand the implicit demands and unexpressed motives underlying this request which have strong links with the unique life-events and emotional experiences of the person. The psychiatrist has a unique role in the contextualization of such a request.

Characteristics and survival of 26 patients with paraneoplastic arthritis.

OBJECTIVE: To date, only a few series of patients with paraneoplastic arthritis have been published. The charts of patients with cancer-associated arthritis were collected in order to describe characteristics of this rheumatism. METHODS: A questionnaire was created for this study and validated by experts based on specific criteria of inclusion and exclusion. Histology of neoplasia was included. RESULTS: In all, 16 males and 10 females with a mean (range) age of 57.5 years (28-85) were recruited from 17 nationwide centres in France. Patients presented with symmetric polyarthritis involving wrists and hands (85%) and extra-articular symptoms were frequent (84%). There was no specific biologic or radiographic feature. The mean (range) delay between the diagnosis of rheumatism and neoplasia was 3.6 months (0-21.2). Tumours were usually diagnosed after articular symptoms occurred (88.5%). Twenty patients had a solid cancer, and six a haematological malignancy. Adenocarcinoma of the lungs was the most frequent type of solid cancer (60%). Tumours were diagnosed at an early stage, which may explain the good median survival of 1.21 years (range 0.64-present) with a mean follow-up of 1.9 years (range 0.16-10). The percentage of articular symptoms resolution was significantly higher in patients with solid tumours, as compared to patients with haemopathy (p = 0.007). In cases of tumour relapse, rheumatic symptoms did not recur for 75% of patients. CONCLUSIONS: Underlying neoplasia should be considered in male patients with new onset polyarthritis, smokers, and particularly in patients chronically ill. Additional investigations should then be performed to diagnose cancer at an early stage.

[Acitretin-induced pneumonia: an underestimated complication of treatment of psoriasis]. / La pneumopathie associée à l'acitrétine: une complication du traitement du psoriasis à ne pas méconnaître.

INTRODUCTION: Retinoids are known to induce side effects which can be severe. Alveolar and interstitial pneumonia of uncertain pathogenesis can rarely occur when retinoid are used among patients with psoriasis. EXEGESIS: We report an observation of acute respiratory distress beginning 26 days after introduction of acitretin, a second-generation retinoid. Treatment withdrawal and corticotherapy allow a spectacular amelioration of respiratory conditions. CONCLUSION: Pneumonia induced by retinoid must be known as a side effect of treatment of psoriasis.

[A young woman with granulomatous mastitis: a corynebacteria may be involved in the pathogenesis of these disease]. / Mastite granulomateuse récidivante chez une jeune femme: rôle potentiel de "corynebacterium kroppenstedtii".

INTRODUCTION: The granulomatous mastitis is an inflammatory pseudotumor of the breast of which evolution benign but likely to generate important morphological after-effects among young women. This anatomoclinic entity of dubious etiology until these last years poses a problem of differential diagnosis with other etiologies of granulomatosis and especially with inflammatory carcinoma of the breast. The infectious theory is actually based on solid arguments and mainly explains the physiopathology of this affection. INTERPRETATION: A 26 years old young woman developed an inflammatory tumor of the left breast of which the catch of load by surgery and an antibiotherapy had shown trailing local continuations and of the esthetic after-effects. One year later, a very inflammatory repetition on the level of the right breast was dealt with in a different way: by steroids and immunomodulating drugs associated with iterative punctures with the purulent collections, the objective being to be less dilapidating that left side. The initial answer was rather favorable and encouraging but the purulent reappearance bulky granulomas with sinus way made reconsider the therapeutic attitude and antibiotics were undertaken after description of a lipophilic corynebactery in the material of puncture (Corynebacteria kroppenstedtii). The effectiveness of the amoxicilline introduced on the data of the antibiogram was undeniable. CONCLUSION: This observation illustrates the therapeutic and diagnostic difficulties of an exceptional affection. Potentially accessible to antibiotics it generally requires a joint surgical assumption of responsibility, at the same time to ensure the histological diagnosis but also with a therapeutic aim. The interest of steroids and the immunomodulation by methotrexate is debatable, these treatments cannot however be conceived without antibiotherapy and sometimes surgery.

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab]. / Maladie de Castleman : désensibilisation rapide après une réaction d'hypersensibilité au rituximab.

INTRODUCTION: Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. CASE REPORT: We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). CONCLUSION: Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative.

Aortic wall mechanics and composition in a transgenic mouse model of Marfan syndrome.

In Marfan syndrome, mutations of the fibrillin gene (FBN1) lead to aneurysm of the thoracic aorta, making the aortic wall more susceptible to dissection, but the precise sequence of events underlying aneurysm formation is unknown. We used a rodent model of Marfan syndrome, the mgR/mgR mouse (with mgR: hypomorphic FBN1 mutation), which underexpresses FBN1, to distinguish between a defect in the early formation of elastic fibers and the later disruption of elastic fibers. The content of desmosine plus isodesmosine was used as an index of early elastogenesis; disruption of elastic fibers was analyzed by histomorphometry. Because disruption of the medial elastic fibers may produce aortic stiffening, so amplifying the aneurysmal process, we measured thoracoabdominal pulse wave velocity as an indicator of aortic wall stiffness. Both mgR/mgR and wild-type (C57BL/6J-129SV) strains were normotensive, and wall stress was not significantly modified because the increase in internal diameter (0.80+/-0.06 vs 0.63+/-0.03 mm in wild type, P<0.05) was accompanied by increased medial cross-sectional area. The aortic wall stiffened (4-fold increase in the elastic modulus-to-wall stress ratio). Desmosine content was not modified (mgR/mgR 432+/-31 vs wild type 492+/-42 microg/mg wet weight, P>0.05). Elastic fibers showed severe fragmentation: the percentage of the media occupied by elastic fibers was 18+/-3% in mgR/mgR mice vs 30+/-1% in wild-type mice, with the number of elastic segments being 1.9+/-0.2 vs 1.4+/-0.1x10(-6)/mm(2) in the wild type (both P<0.05). In conclusion, underexpression of FBN1 in mice leads to severe elastic network fragmentation but no change in cross-linking, together with aortic dilatation. This result suggests that fragmentation of the medial elastic network and not a defect in early elastogenesis is 1 of the determinants of aortic dilatation in Marfan syndrome.

Elastic properties and composition of the aortic wall in old spontaneously hypertensive rats.

We hypothesized that age-linked changes in the composition and elastic properties of the arterial wall occur earlier in hypertensive than in normotensive rats. We evaluated the consequences of hypertension and aging on aortic mechanics, geometry, and composition in 3-, 9-, and 15-month-old awake Wistar-Kyoto rats (WKY) (normotensive) and spontaneously hypertensive rats (SHR) (hypertensive). The elastic modulus of the thoracic aorta, calculated from aortic pulse wave velocity and geometry, was higher in young and adult SHR than in age-matched WKY, as was wall stress; however, isobaric pulse wave velocity and pulse wave velocity-pressure curves were similar. Elastic modulus, isobaric pulse wave velocity, and the slope of the pulse wave velocity-pressure curve dramatically increased in old SHR compared with age-matched WKY; there was no further elevation of blood pressure or wall thickness. Fibrosis did not develop with age in SHR, and the ratio of elastin to collagen decreased in a similar fashion with aging in both strains. In conclusion, although elastic properties of the aortic wall are not intrinsically modified in young and adult SHR in comparison to age-matched WKY, aging is associated with a dramatic stiffening of the aortic wall in old SHR but not in WKY. Changes in blood pressure, aortic wall geometry, or scleroprotein composition do not appear to explain this age-linked aortic stiffening in SHR, suggesting that other mechanisms of disorganization of the media may be involved.

Physical exercise, aortic blood pressure, and aortic wall elasticity and composition in rats.

With a training schedule (8 weeks' treadmill running at 30 m/min up a 10% incline 5 d/wk for 90 min/day), we investigated whether exercise modifies aortic wall dimensions, composition (calcium and elastin content), or stiffness in normotensive 6-month-old male Wistar WAG/Rij rats. Maximal oxygen uptake was measured in half of the rats (n=10 per group). Wall stiffness was evaluated in the other half (9 trained and 10 untrained) on the basis of changes in thoracoabdominal pressure pulse wave velocity and differences in amplitude between the peripheral and central aortic pressure signals. Experiments were performed in nonanesthetized, unrestrained rats and then after pithing. The impact of exercise on the oxidative capacity of the plantaris muscles was evaluated with the measurement of citrate synthase activity. Training increased maximal oxygen uptake by 34% and citrate synthase activity by 40%. Mean peripheral aortic pressure increased by 6% and 19% in trained rats, under awake and pithed conditions, whereas mean central aortic pressure increased by 16%, after pithing only. All indexes of aortic stiffness were similar in trained and control rats, as were aortic wall dimensions, composition, cardiac mass, and heart rate. In conclusion, physical exercise in young rats appears to have no effect on aortic stiffness.

Cardiac consequences of prolonged exposure to an isolated increase in aortic stiffness.

In elderly patients, aortic stiffness is a major determinant of increased end-systolic stress leading to left ventricular (LV) hypertrophy with impaired cardiac performance. However, in a rat model of aortic elastocalcinosis (induced by vitamin D(3)-nicotine [VDN] treatment), brief exposure (1 month) to increased aortic stiffness modified neither cardiac function nor cardiac structure. Here we report the impact of longer exposure (3 months) to aortic stiffness. Three months after induction of aortic stiffness, aortic characteristic impedance was measured in awake rats, 8 control and 10 VDN. Stroke volume was measured (electromagnetic probe) at baseline and after acute volume overload. LV weight/body weight ratio, collagen, and myosin heavy chain (MHC) contents were determined. Although aortic characteristic impedance increased (controls, 32+/-2; VDN rats, 50+/-8 10(3) dyne. s/cm(5); P=0.0248), stroke volume was maintained in VDN rats at baseline (controls, 223+/-18; VDN, 211+/-13 microL) and after volume overload (controls, 378+/-14; VDN, 338+/-15 microL). However, LV weight/body weight ratio (controls, 1.54+/-0.07; VDN, 1.73+/-0.05 g/kg; P=0.0397) and LV collagen content (controls, 31+/-4; VDN, 52+/-4 microgram/g dry wt; P=0.0192) increased. A shift from alpha-MHC (controls, 82+/-2%; VDN, 69+/-3%; P=0.0056) to beta-MHC (controls, 18+/-2%; VDN, 31+/-3%; P=0. 0056) was also observed. Three months' exposure to increased aortic stiffness in VDN rats induced LV hypertrophy with moderate interstitial fibrosis and a shift in the MHC-isoform pattern. Such structural adaptation maintains LV performance.

Activation of metalloproteinase-2, loss of matrix scleroprotein content and coronary artery calcification.

Plaques from the coronary arteries of explanted hearts showed massive calcification (15-fold increase) with a loss of scleroproteins (-36%), an increase in the collagen to elastin ratio (twofold) and activation (+15%) of matrix metalloproteinase-2 (MMP-2). Plaque-free portions of the coronary artery gave results similar to those obtained with the internal mammary artery. There was a significant correlation between plaque calcification and MMP-2 activation, suggesting that the two processes may be linked.

Improving survival of vulnerable infants increases neonatal intensive care unit nosocomial infection rate.

OBJECTIVE: To determine the factors associated with an increasing rate of nosocomial infections in infants with very low birth weights. METHODS: Retrospective review of clinical and nosocomial infection databases for all infants with birth weights of 1500 g or less admitted to an academic neonatal intensive care unit between January 1, 1991, and December 31, 1997 (N = 1184). Two study periods were compared: 1991-1995 and 1996-1997. RESULTS: Among the 1085 infants who survived beyond 48 hours, the proportion who developed nosocomial infections increased from 22% to 31% (P =.001) and the infection rate increased from 0.5 to 0.8 per 100 patient-days (P<.001) during the period from 1996 to 1997. In that same period, the median duration of indwelling vascular access increased from 10 to 16 days (P<.001), and the median duration of mechanical ventilation increased from 7 to 12 days (P<.001). Although the device-specific rate of bloodstream or respiratory infections did not change, the increase in infections was directly attributable to the increasing proportion of infants who required these devices. In both study periods, the peak incidence of initial infection occurred between 10 and 20 days of age. For the entire sample, proportional hazard models identified birth weight, duration of vascular access, and postnatal corticosteroid exposure as significant contributors to the risk of infection. CONCLUSIONS: The increasing number of technology-dependent infants was the primary determinant in the increase of nosocomial infections. Because these infections occur in a small proportion of infants, understanding the host factors that contribute to this vulnerability is necessary to decrease nosocomial infections in neonatal intensive care units.

Age-related arterial calcification in rats.

In man, i) arteries calcify with age and ii) age-linked arterial calcification is amplified by vascular pathology such as hypertension or arteriosclerosis. Age-linked arterial calcification has a bad prognosis but drugs to prevent it are lacking. This is partially due to the lack of appropriate animal models. This paper looks at the extent to which arteries calcify with age in the rat and whether hypertension or arteriosclerosis amplifies such calcification. Total calcium levels were determined by acid digestion and flame spectrophotometry and intracellular calcium levels ([Ca2+]i) by the intracellular calcium-sensitive dye, fura-2. Arteries contained up to 5 times more calcium than other soft tissues. Arteries progressively calcified with age whereas other soft tissues did not. Accumulation of calcium with age was essentially extracellular. Hypertension had no effect on age-related arterial calcification. Calcification of the same order as in man was produced in a rat model of arteriosclerosis (vitamin D plus nicotine treatment). In conclusion, as in man, age-linked, organ-specific arterial calcification does occur in rats but its intensity is far less. Arterial calcification of a similar degree to that observed in man can be obtained in rats by hypervitaminosis D plus nicotine.

Lymphedema combined with brachydactyly and tachycardia.

Hereditary lymphedema can appear at birth or later up to adulthood. It may be seen in connection with diverse symptoms forming various syndromes. The authors report a family with hereditary lymphedema, brachydactyly, syndactyly and tachycardia. Lymphedema and tachycardia could appear together by chance. However this combination could also be a syndrome.

[Acute disulfiram intoxication with severe neurological sequaelae and presenting misleading psychiatric deficiency]. / Intoxication aiguë au disulfirame avec séquelles neurologiques graves et présentation psychiatrique déficitaire trompeuse.

Disulfiram self poisoning is exceptional. The authors report on the case of such an intoxication related to the ingestion of a potentially lethal dose of this drug (30 g) and draw the attention on the following points: 1) The initial signs may be misleading because they include both psychiatrics and neurological signs such as phonation abnormalities, myoclonias and tetraparesia. 2) The evolution is unforseeable with the possible occurrence of severe psychological and motricity sequaelae, associated with bilateral and symetric injuries of the putamen, the palladium and the basal nuclei on CT-scan (or MRI). The pathophysiologic al mechanisms of theses signs are discussed, and the need for disulfiram in the care of alcoholic patients seeking for withdrawal as well.

[Lyme disease disclosed by disabling amyotrophy]. / Maladie de Lyme révélée par une amyotrophie invalidante.

The Lyme disease, which was first found in Lyme, USA, in 1975 is an infectious multi-system disorder whose agent, the Borrelia Burgdorferi, was identified in 1983. Various disease manifestations have been reported since them. We report a case of Lyme disease manifestation in the muscle revealed by serious amyotrophy in the scapular muscles, in the neck and in the trunk with scapula alata accompanied by noctural lumbago which is resistant to non steroïd anti-inflammatory drugs. Electromyography showed patterns of the myogenic type in the serrate anterior and infraspinous muscles on both sides and patterns of the neurogenic peripheral type in the lower extremities. The histological, immunohistochemical and electron-microscopal studies of the muscle biopsy have been without any pathological result. Creatine kinase and aldolase proved normal. Serological antibodies were not significantly increased. A positive diagnosis was obtained by lumbar puncture which showed lymphocytic meningitis, by demonstrating specific antibodies in the cerebrospinal fluid and by Western Blot antibodies analysis. Efficacy of the antibiotic therapy has resulted in a rapid regression of the symptoms, which is a further confirmation of the previous diagnosis.

[Yellow nail syndrome. Apropos of 2 cases. Review of the literature]. / Syndrome des ongles jaunes. A propos de deux cas. Revue de la littérature.

The yellow nail syndrome is a clinical syndrome without specific biological parameters. It is characterized by the following threesome of symptoms: nail abnormalities, primary lymphedema, and pleuropulmonary manifestations. In most cases lymphography shows abnormalities of the lymphatic vessels and spirometry shows a restrictive defect and rarely obstructive disorders. Pathogenesis of this syndrome is still unknown. It is, however, remarkable that the yellow nail syndrome may occur in association with other diseases, the most frequent of which are cancer affections and immune disorders. We report two cases of the yellow nail syndrome which were associated with cancer (neoplasm of the larynx and breast).

[Von Recklinghausen's disease associated with pancreatic somatostatinoma]. / Maladie de Von Recklinghausen associée à un somatostatinome pancréatique.

INTRODUCTION: Pancreatic somatostatinoma is a rare entity and its association with Von Recklinghausen's disease has only been described on two occasions. We report a new observation, with clinical and evolving status differing from those described in isolated cases of somatostatinoma. OBSERVATION: A 28 year-old man presenting with familial Von Recklinghausen's disease, had suffered for 10 years from paroxysmic abdominal pain. He was hospitalized for intense pain. Imaging revealed a retroperineal tumoral formation. Following duodenopancreatectomy, somatostatinoma was diagnosed. Diffuse metastatic miliary was revealed and multiple glandular metastases. DISCUSSION: Other than the rarity of the morbid association (pancreatic somatostatinoma and Von Recklinghausen's disease) described, this case is particular in that the patient was very young, symptomatology was unapparent and tumoral evolution was minimal.

[Campylobacter fetus meningitis in adults]. / Méningite à Campylobacter fetus chez l'adulte.

Campylobacter fetus is an uncommon cause of meningitis in the adult. We report a case observed in an 84-year-old man with alcoholic cirrhosis. The patient presented fever, jaundice and a state of mental confusion. Blood and cerebrospinal fluid cultures identified Campylobacter fetus sensitive to several antibiotics. Ciprofloxacine-ceftriaxone combination replaced the antibiotics prescribed empirically prior to identification and led to regression of the fever and normal mental status within 4 days. Spinal tap on day 7 showed 20 white cells, 85% lymphocytes and normal protein level. Unfortunately, the patient later developed edema and ascitis with major jaundice. Oligo-anuria could not be controlled and the patient died two weeks after admission. Campylobacter fetus meningitis is predominantly seen in men, mean age of onset 50 years. Clinical signs are not specific and diagnosis can only be obtained on the basis of cerebrospinal fluid results. Adapted antibiotics are required.

[Budd-Chiari syndrome with inferior vena cava stenosis]. / Un syndrome de Budd-Chiari par sténose cave inférieure.

BACKGROUND: Stenosis of the inferior vena cava is a rare cause of Budd-Chiari's syndrome. We report on such a case related to a specific cause with a dramatic improvement after endovascular treatment. CASE REPORT: A 53-year old woman was admitted to hospital because she demonstrated circulatory collapse, inferior limbs edema and post-prandial epigastralgia. These signs were related to the occurrence of a stenosis of the sus-hepatic segment of the inferior vena cava related to the presence of the distal part of a catheter. An angioplasty with the insertion of a stent was followed by a total recovery with a one-year survey. CONCLUSION: Angioplasty with the insertion of a stent should be considered in a Budd-Chiari syndrome related to the stenosis of the inferior vena cava. This option should be evaluated with reference to classic surgical techniques.