[First junior doctors: State of play one year after the implementation of the consolidation phase within the diploma of specialized studies in internal medicine and clinical immunology]. / Premiers docteurs juniors : état des lieux à un an de la mise en place de la phase de consolidation au sein du diplôme d'études spécialisées de médecine interne et immunologie clinique.

INTRODUCTION: The 2017 reform of the 3rd cycle of medical studies introduced the concept of supervised autonomy with the creation of a new junior doctor (JD) status. The aim of this work was to interview the first class of JDs in internal medicine and clinical immunology (IMCI) regarding the progress and implementation of this final year of internship. METHODS: The IMCI JDs were invited to complete an anonymous online survey, contacted by email and social networks. RESULTS: The questionnaire received 36 responses out of an estimated fifty JDs. The majority of JDs spent more than 70% of their time on conventional hospitalisation and less than 20% on scheduled hospitalisation. Most of them would have preferred to do more consultations and provide expert counsels. Weekly working hours were not respected for the majority of JDs. Personal education and academic formation were not respected for 77.8% of JDs. Overall, 75% were satisfied with their empowerment and 88.6% felt that the transition to post residency would be easier with the consolidation phase. A third reported that their residency had confirmed their apprehension about practising as an internist, and even that this apprehension might call into question their future practice. CONCLUSION: This survey is an initial assessment of the implementation of the JD year in the IMCI residency. A collective effort around this last year of internship seems to be essential to ensure the personal and professional development of young internists.

The other great imitator among infectious diseases: Leptospirosis.

INTRODUCTION: Leptospirosis is a worldwide zoonosis responsible for highly diverse clinical presentations with a wide range of severity. Variable environment exposures to infected urines of rodents have been described. OBSERVATION: We report five cases of serologically confirmed leptospirosis leading to hospitalization in an intensive care unit (ICU) of a French center. These patients displayed neurological, respiratory, and abdominal presentation of leptospirosis with variable level of severity. Either professional, leisure related, or daily living exposures have been retrieved. CONCLUSION: These cases underline the diversity of clinical presentation and environmental exposure of this infectious disease. They highlight the interest of an exhaustive anamnesis with collection of professional activity, environmental exposures, and leisure activities.

Invasive aspergillosis and endocarditis.

INTRODUCTION: Aspergillusfumigatus can cause a systemic infection called invasive aspergillosis causing pulmonary and extra-pulmonary damage. Aspergillus endocarditis (AE) is a relatively rare disease but can be life-threatening. CASE REPORTS: We report here on five cases of endocarditis due to invasive aspergillosis: a 58-year-old man receiving immunosuppressive medication following a kidney graft, a 58-year-old man undergoing chemotherapy for chronic lymphocytic leukaemia, a 55-year-old man receiving corticosteroids for IgA vasculitis, a 52-year-old HIV-infected woman under no specific treatment and a 17-year-old boy under immunosuppressive therapy for auto-immune chronic neutropenia. DISCUSSION: Aspergillus accounts for 25-30% of fungal endocarditis and 0.25% to 8.5% of all cases of infectious endocarditis. Aspergillus endocarditis results from invasion of the lung arterioles by hyphae and blood dissemination. It is associated with a very high mortality rate (42-68%). Diagnosing Aspergillus endocarditis is mainly problematic because blood cultures are almost always negative, and fever may be absent. Immunosuppression, haematological malignancies, recent cardiothoracic surgery, negative blood cultures with endocarditis and/or systemic or pulmonary emboli are predictors of AE. In the setting of endocarditis, some clinical characteristics may raise early suspicions of aspergillosis rather than a non-fungal agent: no fever, vegetations affecting the mitral valve, non-valve or aortotomy sites, aortic abscess or pseudo-aneurysm. The identification of invasive aspergillosis is based on a chest CT scan, microscopy/culture or other serological and molecular tests. The treatment of Aspergillus endocarditis requires triazole antifungal drugs, and frequently additional surgical debridement. CONCLUSION: Aspergillus endocarditis is rare but is associated with a very high mortality rate. Knowledge of its predictive factors and key clinical features can help to differentiate aspergillosis from non-fungal endocarditis and may enable improved survival rates.

Anti-Ma2 antibody encephalitis associated with Sjogren's syndrome.

INTRODUCTION: Onconeuronal antibodies directed against intracellular antigens are strongly associated with paraneoplastic syndromes and their detection in the absence of cancer is unusual. We herein report a case of anti-Ma2 encephalitis associated with Sjogren's syndrome (SS). CASE REPORT: An 81-year-old woman followed for a cutaneous lupus with vasculitis associated with SS presented a flare of her disease with neurological worsening including walking difficulty, hypersialorrhea and dysphagia. A paraneoplastic origin of the symptoms was suspected and anti-Ma2 antibodies were positive in serum. The search for an underlying neoplasia was negative. The diagnosis of anti-Ma2 encephalitis secondary to a SS was made. In the literature, the association of anti-Ma2 encephalitis and SS has been previously reported twice. Cases of patients with other onconeuronal antibodies associated with SS have been also reported. Anti-Ma2 encephalitis is a rare condition with a wide spectrum of symptoms associated with a cancer in more than 90% of the cases. Anti-Ma2 encephalitis has also been described after the use of immune check points inhibitors underscoring the role of autoimmunity in its pathogenesis. CONCLUSION: Anti-Ma2 encephalitis is essentially associated with neoplasia but can occur in Sjogren's syndrome.

[An abscessed granulomatous prostatitis]. / Une prostatite granulomateuse abcédée.

INTRODUCTION: Prostatic abscesses are usually diagnosed in the setting of bacterial prostatitis. Rarely, they reveal or complicate granulomatous prostatitis. CASE REPORT: A 55-year-old man was admitted for acute urinary retention. Urine culture was sterile, with leukocyturia > 106/ml. After failure of antibiotic therapy with cefotaxime, CT scan revealed a necrotic prostatic collection and a nodular non-necrotic tissular lesion in the left upper lung lobe. Trans-rectal drainage of the prostatic lesion and lung biopsies revealed granuloma with multinucleated giant cells (without mycobacteria). The diagnosis of granulomatosis with polyangiitis was confirmed by high level of anti-proteinase 3 antibodies. Treatment with steroids and rituximab resulted in apyrexia, regression of the inflammatory syndrome and clinical manifestations. CONCLUSION: The diagnosis of granulomatosis with polyangiitis should be considered in the presence of a non-infectious granulomatous prostatitis with systemic involvement.

[A tularemia mimicking lymphoma]. / Une tularémie mimant un lymphome.

INTRODUCTION: Adenopathies are a frequent cause of recourse in internal medicine. When histological analysis reveals the presence of granuloma, multiple infectious or non-infectious etiologies are considered. If diagnoses of lymphoma, sarcoidosis or tuberculosis are easily mentioned, tularemia should also be considered in the differential diagnosis. OBSERVATION: A 54-year-old patient had a fever at the evening with night sweats and a cough resistant to two lines of antibiotics. A thoraco-abdomino-pelvic CT scan revealed hilar and mediastinal adenopathies that appeared hypermetabolic with PET-TDM, as well as pulmonary nodules. A PCR performed on lymph node biopsy and serology allowed the diagnosis of tularemia. The evolution was favourable after antibiotic treatment. CONCLUSION: The association of fever, night sweats, altered general state and mediastinal adenopathies should be considered as a diagnosis of tularemia. Ganglionic biopsy, combined with molecular biology techniques and serology, can confirm the diagnosis.

In-depth exploration of the photophysics of a trinuclear palladium complex.

A detailed theoretical and spectroscopic study on the electronically excited states of a trinuclear palladium complex is presented both in the gas phase and solution. The application of DFT and TDDFT methods as well as a variety of spectroscopic methods to the chosen complex [Pd3{Si(mt(Me))3}2] (1, mt(Me) = methimazole) leads to the first detailed analysis of the photophysics of a symmetric trinuclear complex. In combination with the calculations, energies, structures and lifetimes of the excited electronic states (with an (3)A1 state as the lowest one) are characterized by applying the resonant-2-photon-ionization method in a molecular beam experiment as well as luminescence, time-correlated single photon counting and excited state femtosecond absorption spectroscopy in solution. These investigations are of fundamental interest to analyze photophysical properties of metal containing complexes on a molecular level.

Modulation of gastrointestinal function by MuDelta, a mixed µ opioid receptor agonist/ µ opioid receptor antagonist.

BACKGROUND & PURPOSE: Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound ('MuDelta'), could normalize GI motility without constipation. EXPERIMENTAL APPROACH: MuDelta was characterized in vitro as a potent µ opioid receptor agonist and high-affinity δ opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic δ opioid receptor immunoreactivity was quantified. KEY RESULTS: δ Opioid receptor antagonism opposed µ opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically-mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated δ opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post-inflammatory model. CONCLUSIONS AND IMPLICATIONS: MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome.

Combined theoretical and experimental study of spin and charge dynamics on the homodinuclear complex [Ni2(II)(L-N4Me2)(emb)].

We present a combined theoretical and experimental study of spin and charge dynamics on the homodinuclear compound [Ni2(II)(L-N4Me2)(emb)]. The theoretically calculated oscillator strengths of the ground-state absorption spectrum show an acceptable agreement with experiment. We predict a local ultrafast laser-induced spin-flip scenario, which involves charge-transfer states. Experimentally, we observe charge dynamics on two different time scales. The two relevant, transient electronic states and their electronic properties are also theoretically characterized. These results provide a joint investigation of the homodinuclear complex and suggest a realistic scenario for ultrafast spin dynamics and other optical-related manipulations.

Prokineticin-1 evokes secretory and contractile activity in rat small intestine.

BACKGROUND: Prokineticins 1 and 2 (PROK1 and PROK2) are so named because they contract gastrointestinal smooth muscle, yet little else is known about their role in gastrointestinal function. Therefore, we used a combination of approaches to elucidate the mechanisms by which PROK1 alters ileal contractility and secretion in rats. METHODS: RT-PCR and immunofluorescence were used to determine PROK and receptor (PK-R) mRNA levels and PK-R1 localization, respectively. Upper GI transit and fluid secretion were determined in vivo. Contractility and intestinal epithelial ion transport were assessed in isolated ileal segments. KEY RESULTS: In the gastric fundus, PROK1 mRNA is highly expressed (70-fold >PROK2 mRNA) whereas the ileum has the highest mRNA expression of its receptor. PK-R1 immunoreactivity is visualized in ileal crypt cells, and in submucosal and myenteric neurons. In ileal segments, PROK1 evokes biphasic contractile responses consisting of an early, TTX-sensitive response (EC(50) = 87.8 nmol L(-1)) followed by a late, TTX-insensitive (EC(50) = 72.4 nmol L(-1)) component that is abolished in mucosa-free preparations. Oral administration of PROK1 enhances small bowel transit (111 +/- 3% of control) and fluid secretion (340 +/- 90% of control) and in muscle-stripped ileal preparations increases short-circuit current (EC(50) = 8.2 nmol L(-1)) in a TTX-insensitive manner. The PROK1-evoked Cl- secretion is reduced by piroxicam (non-selective cyclooxygenase inhibitor), and a prostaglandin EP(4) receptor antagonist (AH23848), but not a thromboxane receptor antagonist (GR32191B). CONCLUSIONS & INFERENCES: These results demonstrate that PROK1 has oral prokinetic and secretogogue activity and that it acts on the intestinal mucosa via PK-R1 and prostaglandin receptors to mediate these effects.