[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.

[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.

[Immune-mediated necrotizing myopathy associated with antibodies to hydroxy-methyl-glutaryl-coenzyme A reductase]. / Myopathie nécrosante auto-immune associée aux anticorps anti-hydroxy-méthyl-glutaryl-coenzyme A réductase.

INTRODUCTION: Statins or 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (HMGCR) are among the most commonly prescribed treatment in France. They may be responsible for muscular intolerance with variable severity. They have been recently involved in the occurrence of an acquired inflammatory myopathy associated with anti-HMGCR antibodies. This new type of toxic myopathy remains poorly known by clinicians. OBSERVATION: We report a 61-year-old woman treated with a statin for many years who developed a lower and upper limb disabling myopathy with a rapid unfavourable course despite treatment withdrawal. Clinical history and investigations, especially including an assay for anti-HMGCR antibodies led to the diagnosis of autoimmune necrotizing myopathy with anti-HMGCR antibodies. Subsequent initiation of an immunosuppressive treatment by corticosteroids and methotrexate was effective. CONCLUSION: Statins may unmask or cause an autoimmune necrotizing myopathy associated with the presence of anti-HMGCR antibodies. Their identification is now routinely available. An immunosuppressive treatment is necessary and justified by the autoimmune nature of the disease.

[Clinical and biological efficacy of tocilizumab in giant cell arteritis: report of three patients and literature review]. / Efficacité clinique et biologique du tocilizumab au cours de la maladie de Horton : à propos de trois observations et revue de la littérature.

INTRODUCTION: Treatment of giant cell arteritis is based on prolonged corticosteroid therapy but adverse side effects are common especially in the elderly. CASE REPORTS: We report three patients with giant cell vasculitis treated by tocilizumab, an interleukin-6 receptor antibody, owing to resistance or intolerance to corticosteroid therapy. A favorable outcome was rapidly observed both on clinical and biological data allowing a corticoid therapy sparing. CONCLUSION: Tocilizumab is a promising treatment of giant cell arteritis but controlled trials are needed to confirm its efficacy.

[Acquired Gitelman syndrome associated with Sjögren's syndrome and scleroderma]. / Syndrome de Gitelman acquis au cours d'un syndrome de Gougerot-Sjögren associé à une sclérodermie.

Tubulopathy can complicate autoimmune diseases. It is usually a distal tubular acidosis, but Fanconi syndrome or Bartter syndrome has been exceptionally reported. We report a case of acquired Gitelman syndrome in a 32-year-old male who also presented diffuse scleroderma autoimmune thyroiditis, and Sjögren's syndrome. Only three cases of Sjögren syndrome associated with Gitelman syndrome have been previously reported in literature. The absence of other cases in the family and absence of mutation SLC12A3 emphasise the relation between autoimmune disease and this tubulopathy.

[Recurrent nerve palsy due to Lyme disease: report of two cases]. / Paralysie du nerf récurrent au cours d'une maladie de Lyme : à propos de deux observations.

INTRODUCTION: Neuroborreliosis can be a difficult diagnosis which requires epidemiologic, clinical and biologic arguments. CASE REPORTS: We report two patients who presented with a recurrent laryngeal nerve palsy with positive Lyme serology and favorable outcome after antibiotic therapy. In one case, a lymphocytic meningitis with intrathecal production of specific antibodies was evidenced. CONCLUSION: Recurrent laryngeal nerve palsy is an uncommon manifestation of neuroborreliosis. Lyme serology is an important tool when neurologic disorder occurs because of an atypical course of Lyme disease.

[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.

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.

[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.

Withdrawal reveals lack of effect of prolonged antihypertensive treatment on intrinsic aortic wall stiffness in senescent spontaneously hypertensive rats.

1. Chronic antihypertensive treatment lowers cardiovascular morbidity and mortality. The beneficial effect on the blood vessel wall may be due to the lowering of blood pressure (BP) and, hence, wall stress (WS), or to a treatment-induced change in wall structure. 2. We have previously shown that, when evaluated at the same level of BP and WS, the stiffness of the aortic wall of old spontaneously hypertensive rats (SHR) is higher than that of young and adult SHR and that of age-matched Wistar-Kyoto (WKY) rats. In the present study, we tested the hypothesis that the intrinsic changes in wall composition and mechanics in old SHR can be modulated by long-term treatment with an angiotensin I-converting enzyme inhibitor (captopril; 40 mg/kg per day) combined with a diuretic (hydrochlorothiazide; 20 mg/kg per day) and that treatment withdrawal would reveal whether such changes are maintained when BP and WS return to pretreatment levels. 3. We evaluated aortic structure and mechanics in SHR following 1 week withdrawal of oral antihypertensive treatment from 3 to 15 months of age (n = 8). Results were compared with age-matched SHR that were maintained on treatment (n = 12) or were not treated (n = 13) and with WKY rats (no treatment n = 11; maintained n = 11; withdrawn n = 10). 4. Isobaric aortic wall stiffness was estimated from the ratio of baseline aortic pulse wave velocity (PWV) to BP and the slope relating aortic PWV to BP following sodium nitroprusside-induced hypotension. Relative wall stiffening was estimated as the ratio of elastic modulus (EM) to WS. We argued that if treatment produced a change in wall elastin or collagen content, with a subsequent decrease in isobaric wall stiffness, then this would be maintained when BP increased following withdrawal of treatment. 5. In old SHR, treatment lowered isobaric wall stiffness (baseline PWV/BP 4.6 +/- 0.3 cm/s per mmHg; slope relating PWV to BP 6.7 +/- 0.4 x 10-3 cm/s per mmHg and EM/WS 4.1 +/- 0.4 vs 6.1 +/- 0.4 cm/s per mmHg, 9.7 +/- 0.9 x 10-3 cm/s per mmHg and 8.9 +/- 1.1, respectively, without treatment; all P < 0.05). After 1 weeks treatment withdrawal, the indices (5.7 +/- 0.2 cm/s per mmHg, 9.1 +/- 0.2 x 10-3 cm/s per mmHg and 7.2 +/- 0.6) increased in parallel with the increase in WS to levels similar to those observed in untreated SHR. There were no significant differences among the WKY rat groups. 6. Treatment increased the elastin and collagen contents of the aortic wall in both SHR (196 +/- 13 and 128 +/- 5 vs 111 +/- 9 and 86 +/- 4 mg/g wet weight, respectively, in untreated; P < 0.05) and WKY rats (190 +/- 19 and 135 +/- 4 vs 115 +/- 7 and 114 +/- 5 mg/g wet weight, respectively, in untreated; P < 0.05). This increase remained following withdrawal (213 +/- 26 and 118 +/- 4 vs 161 +/- 14 and 127 +/- 4 mg/g wet weight in SHR and WKY rats, respectively). 7. In summary, 1 year of treatment with captopril plus hydrochlorothiazide increases wall elastin content and reduces WS and stiffness in old SHR. Following withdrawal, elastin content remains high, but wall stiffness parallels WS in a manner similar to that in untreated SHR.

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.

Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats.

With aging, the aortic wall becomes stiffer. This could be because of changes in wall stress or composition. We investigated whether a specific change in wall composition, ie, accumulation of advanced glycation end products (AGEs) on the extracellular matrix, is a major factor. We measured aortic mechanics, geometry, and composition in 3-, 10-, 15-, 20-, and 30-month-old inbred normotensive Wistar-Glaxo/Rijswick rats and in a group of 30-month-old rats treated from 20 months onward with aminoguanidine (AG, 42 mg/kg per day), an inhibitor of AGE formation. Thoracoabdominal aortic (pressure) pulse-wave velocity (PWV) increased progressively with age (44% from 3 to 30 months). This age-related increase in aortic PWV was not related to changes in wall stress. For all ages, central (and peripheral) aortic mean blood pressures were not statistically different. Dilatation occurred (18% increase in internal diameter from 3 to 30 months), but this was accompanied by outward hypertrophic remodeling, with an increase in the medial cross-sectional area of 95% and in the ratio of medial thickness to internal diameter of 29%. Wall stress decreased with age (-34%). There was an increase in the ratio of elastic modulus (calculated from the Moens-Korteweg equation) to wall stress (calculated from the Lamé equation, 117% from 3 to 30 months), suggesting that a change in the composition of the wall is responsible for the age-linked increase in wall stiffness. Dry weight decreased slightly but significantly (-14%) with age. Total protein, elastin, collagen, and nonscleroprotein protein [total-(elastin+collagen)] contents did not change with age, but calculated densities of all 4 were halved (as the medial cross-sectional area doubled). The elastin/collagen ratio was statistically similar at all ages. The only significant effect of AG treatment was a fall in PWV (-20%), leading to a fall in the elastic modulus/wall stress ratio (-27% at 10 months of AG treatment versus 30 months of no treatment). In conclusion, the age-related increase in aortic wall stiffness is prevented by 10 months of treatment with AG, which has no effect on wall stress or composition, suggesting that AG may improve aortic wall stiffness by lowering the degree of AGE-induced cross-linking of the extracellular matrix scleroproteins, such as collagen.

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.