Ibuprofen can induce syndrome of inappropriate diuresis in healthy young patients.

A 30-year-old caucasian woman, without past medical history or known drug use, was admitted to the emergency department for persistent fever and arthralgias. The laboratory analysis showed moderate hypoosmolar hyponatremia (Na: 132 mmol/L, osmolality: 239 mOsm/L), normal sodium excretion (<20 mmol/L), and a high urinary osmolality (415 mOsm/L). Later, she deteriorated with seizures and deeper hyponatremia (Na: 113 mmol/L) and so was moved to the critical care unit. At first, no obvious aetiology was found, the patient was euvolemic, as she was well hydrated and lacked concerning findings of heart failure, renal disease, or liver cirrhosis. A syndrome of inappropriate diuresis (SIAD) was proposed, and corrective measures were started immediately to reduce her hyponatremia, including restriction of fluid intake. The administration of intravenous hypertonic saline solution permitted normal neurological status to be restored and corrected the sodium concentration but induced reversible acute renal failure. Further investigation revealed that the patient had ingested 8 g ibuprofen two days before admission. After other aetiologies were ruled out, drug-induced SIAD due to ibuprofen was the most likely diagnosis for this patient. SIAD-associated hyponatremia and acute renal failure are rare side effects of nonsteroidal anti-inflammatory drugs, particularly in young people. Therefore, this case may represent a unique case of NSAID-induced SIAD and highlight the need to obtain thorough medication histories and exclude all other potential causes in hyponatremic patients.

Morbidity and impaired quality of life 30 months after chikungunya infection: comparative cohort of infected and uninfected French military policemen in Reunion Island.

We compared the morbidity and quality of life of military policemen ("gendarmes") infected with chikungunya virus (CHIKV+) 30 months after contamination. We categorized the subjects in 3 groups: healed patients (n = 48), non-healed patients (n = 37, 44% of CHIKV+), and uninfected subjects (CHIKV-, n = 297). Data were self-recorded in this retrospective cohort study; they included sociodemographic information, clinical symptoms, and the Medical Outcome Study 36-item short-form health survey (MOS-SF36) quality of life questionnaire. The study population was mostly men (92%), with a median age of 42.8 years, regardless of CHIKV status. The main complaints were rheumatic symptoms (pain, stiffness, and swelling), reported 5 times more often by non-healed CHIKV+ subjects and 2-3 times more often by healed CHIKV+ subjects than by CHIKV- subjects, and fatigue. The CHIKV+ patients reported more use of health care services. Thirty months after infection, all rheumatic symptoms were more frequent and intense among CHIKV+ than among CHIKV- subjects, with a gradient of severity between healed and non-healed CHIKV+ subjects. Non-healed CHIKV+ subjects reported subsequent limitation in their activities. All dimensions of MOS-SF36 as well as physical and mental component summaries were impaired in CHIKV+ compared to CHIKV- subjects, with a decreasing gradient of impairment from non-healed to healed CHIKV+ subjects, then to CHIKV- subjects. These observations confirm the long-term impact of CHIKV infection on both physical and mental health. Questions persist regarding the duration of this impairment and the possibility of a return to "before CHIKV" health status for infected patients.

[Severe lactic acidosis due to metformin: report of 3 cases]. / Acidose lactique sévère par intoxication accidentelle à la metformine : à propos de 3 observations.

Metformin, an oral antidiabetic drug, is the sole representative of the biguanide class available in France. Because of its beneficial effects on weight and cardiovascular level, it represents the standard treatment for type 2 diabetic obese patients. Lactic acidosis associated with metformin is a rare but serious complication that can occur in these patients, particularly when intercurrent episode promotes the accumulation of this molecule. We report three cases in which the toxic origin of acidosis has been objectified by the plasma assay and intra-erythrocyte metformin. Curative treatment is based on renal replacement therapy, but the main treatment is preventive, requiring compliance with the cons-indications and rules of prescription of this drug.

Forty-minute endovascular aortic occlusion increases survival in an experimental model of uncontrolled hemorrhagic shock caused by abdominal trauma.

BACKGROUND: To evaluate the feasibility of aortic balloon catheter occlusion in intra-abdominal hemorrhage. METHODS: Effects of transfemoral diaphragmatic aortic balloon occlusion (ABO) have been evaluated in 25 pigs. The animals were submitted to incontrollable hemorrhage by a splenic trauma. Group 1 (n = 9) received fluid resuscitation with normal saline (NS) without aortic occlusion; group 2 (n = 8) underwent 60 minutes ABO and NS. Groups 3 (n = 4) and 4 (n = 4) underwent ABO during 40 minutes and 60 minutes, respectively, NS, and splenectomy. RESULTS: Aortic balloon location was adequate in all animals. ABO increased the portion of 2-hour survivors significantly (7/16 vs. 0/9; p = 0.03). ABO increased mean arterial blood pressures (p < 0.05). There was a significant decrease of bleeding and volume of fluid resuscitation (p < 0.05) in ABO groups. Blood potassium and lactate levels at death were significantly higher in groups 2 and 4 compared with those of the control group: 29 ± 0.54 and 6.08 mmol/L ± 0.44 mmol/L versus 4.16 mmol/L ± 0.35 mmol/L (p < 0.02), and 11.39 mmol/L ± 0.37 mmol/L and 9.59 mmol/L ± 1.19 mmol/L versus 6.43 mmol/L ± 0.57 mmol/L (p < 0.001), respectively. There were no significant differences between group 3 and the control group: 4.83 mmol/L ± 0.32 mmol/L versus 6.43 mmol/L ± 0.57 mmol/L and 5.2 mmol/L ± 0.13 mmol/L versus 4.16 mmol/L ± 0.35 mmol/L, respectively. At necropsy, there were no significant differences in terms of visceral (bowel and kidney) ischemia between the different experimental groups. CONCLUSION: A 40-minute ABO followed by surgical damage control improved survival in this animal model of uncontrolled hemorrhagic shock caused by abdominal trauma. ABO could be considered for the management of severe abdominal trauma.

[Pancytopenia and folate deficiency: a case report]. / Pancytopénie et carence en folates : à propos d'un cas.

Anemia is the most common pathology encountered in hematology. Etiologies are numerous, so it is important to adopt a rigorous approach. Complementary examinations must be specific to the clinical situation in order to determine the mechanisms on the one hand and decide the therapeutic management on the other. We report the observation of a case of sudden onset of profound pancytopenia. Investigation led to the diagnosis of major folic acid deficiency with favorable evolution. Through this case, we describe the diagnostic approach towards anemia and the mechanisms involved in the formation of folate deficiency.

5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases.

PURPOSE: 5-Fluorouracil (5-FU) is a mainstay for treating various solid tumours in adults, including digestive and head and neck cancers. 5-FU-related toxicities usually include haematological, digestive and cutaneous features. Additionally, 5-FU has been described as being potentially neurotoxic in patients, but these side effects are quite rare in clinical practice. Here, we report two cases of sudden and unpredictable drug-induced neurotoxicities that occurred in patients undergoing their first course of 5-FU-based chemotherapy. PATIENTS AND METHODS: None of these patients had any previous neurological disorder history, and both were treated following standard regimen (LV-5-FU2 and TPF for patient 1 and 2, respectively). Neurotoxicity included drowsiness, acute confusion plus dysarthria for the first patient and seizure, confusion and signs of metabolic encephalopathy for the second one. In addition, typical 5-FU-related severe toxicities (e.g. neutropenia and mucosities) were observed. Both patients slowly recovered from these neurological toxicities under supportive treatment. It was assumed that overexposure to 5-FU could explain the severe toxicities encountered. To test this hypothesis, we retrospectively evaluated the dihydropyrimidine dehydrogenase (DPD) activity of these patients on a phenotypic basis. RESULTS: Evaluation of the uracil-to-di-hydrouracil (U/UH2) ratio in plasma revealed a profound DPD deficiency syndrome in both patients. CONCLUSION: These cases suggest that 5-FU standard dosage administration may lead to strong overexposure, responsible for the severe toxicities observed, including the neurological features. It implies that DPD deficiency can cause neurotoxicity in 5-FU-treated patients and advocates for the prospective screening of DPD deficiency before starting any 5-FU-containing chemotherapy so as to prevent such side effects in the future.

Chikungunya virus infection.

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes, mostly Aedes aegypti and Aedes albopictus. After half a century of focal outbreaks of acute febrile polyarthralgia in Africa and Asia, the disease unexpectedly spread in the past decade with large outbreaks in Africa and around the Indian Ocean and rare autochthonous transmission in temperate areas. This emergence brought new insights on its pathogenesis, notably the role of the A226V mutation that improved CHIKV fitness in Ae. albopictus and the possible CHIKV persistence in deep tissue sanctuaries for months after infection. Massive outbreaks also revealed new aspects of the acute stage: the high number of symptomatic cases, unexpected complications, mother-to-child transmission, and low lethality in debilitated patients. The follow-up of patients in epidemic areas has identified frequent, long-lasting, rheumatic disorders, including rare inflammatory joint destruction, and common chronic mood changes associated with quality-of-life impairment. Thus, the globalization of CHIKV exposes countries with Aedes mosquitoes both to brutal outbreaks of acute incapacitating episodes and endemic long-lasting disorders.

The challenge of diagnosing Plasmodium ovale malaria in travellers: report of six clustered cases in French soldiers returning from West Africa.

BACKGROUND: Plasmodium ovale is responsible for 5% of imported malaria in French travellers. The clinical and biological features of six clustered cases of P. ovale malaria in an army unit of 62 French soldiers returning from the Ivory Coast are reported. CASE REPORT: All patients were symptomatic and developed symptoms on average 50 days after their return and 20 days after the end of chemoprophylaxis (doxycycline). Clinical features included fever (6/6), mostly tertian (4/6), aches (6/6), nausea (3/6), abdominal pain (2/6), diarrhoea (2/6), or cough (2/6). Thrombocytopaenia was lower than 100,000/mm3 in half the cases only, and the haemoglobin count was normal for all patients. The diagnosis was made after at least three thick and thin blood smear searches. Parasitaemia was always lower than 0.5%. All rapid diagnostic tests were negative for HRP2 and pLDH antigens. DISCUSSION: Plasmodium ovale malaria is currently a problem to diagnose in travellers, notably in French soldiers returning from the Ivory Coast. Early attempts at diagnosis are difficult due to the lack of specific clinical features, the rarity of biological changes and the poor sensitivity of diagnostic tools to detect low parasitaemia. Thus, the diagnosis is commonly delayed or missed. Physicians should be aware of this diagnostic challenge to avoid relapses and provide prompt and adequate treatment with chloroquine and radical cure with primaquine.

Persisting mixed cryoglobulinemia in Chikungunya infection.

BACKGROUND: Chikungunya virus (CHIKV), an arbovirus, is responsible for a two-stage disabling disease, consisting of an acute febrile polyarthritis for the first 10 days, frequently followed by chronic rheumatisms, sometimes lasting for years. Up to now, the pathophysiology of the chronic stage has been elusive. Considering the existence of occasional peripheral vascular disorders and some unexpected seronegativity during the chronic stage of the disease, we hypothesized the role of cryoglobulins. METHODS: From April 2005 to May 2007, all travelers with suspected CHIKV infection were prospectively recorded in our hospital department. Demographic, clinical and laboratory findings (anti-CHIKV IgM and IgG, cryoglobulin) were registered at the first consultation or hospitalization and during follow-up. RESULTS: Among the 66 travelers with clinical suspicion of CHIKV infection, 51 presented anti-CHIKV IgM. There were 45 positive with the serological assay tested at room temperature, and six more, which first tested negative when sera were kept at 4 degrees C until analysis, became positive after a 2-hour incubation of the sera at 37 degrees C. Forty-eight of the 51 CHIKV-seropositive patients were screened for cryoglobulinemia; 94% were positive at least once during their follow-up. Over 90% of the CHIKV-infected patients had concomitant arthralgias and cryoglobulinemia. Cryoglobulin prevalence and level drop with time as patients recover, spontaneously or after short-term corticotherapy. In some patients cryoglobulins remained positive after 1 year. CONCLUSION: Prevalence of mixed cryoglobulinemia was high in CHIKV-infected travelers with long-lasting symptoms. No significant association between cryoglobulinemia and clinical manifestations could be evidenced. The exact prognostic value of cryoglobulin levels has yet to be determined. Responsibility of cryoglobulinemia was suspected in unexpected false negativity of serological assays at room temperature, leading us to recommend performing serology on pre-warmed sera.

Chikungunya virus-induced myopericarditis: toward an increase of dilated cardiomyopathy in countries with epidemics?

The acute stage of infection with chikungunya virus, which is characterized of fever, polyarthritis, and occasional rash, can be complicated by myocarditis, as reported in a 21-year-old woman. Persisting changes on cardiac magnetic resonance imaging one year after disease onset could lead to delayed myocardial damage. An unexpected delayed increase in dilated cardiomyopathy may be observed in countries affected by the outbreak of chikungunya virus disease during 2005-2007.

Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases.

A large chikungunya virus (CHIKV) outbreak emerged in 2005-2006 in the Indian Ocean islands, including Comoros, Mayotte, Mauritius, the Seychelles, and particularly in Reunion Island where 35% of 770,000 inhabitants were infected in 6 months. More recently, circulation of the virus has been documented in Madagascar and in India where CHIKV is spreading rapidly. CHIKV-infected visitors have returned home to nonendemic regions from these islands. We conducted a 14-month prospective observational study on the clinical aspects of CHIKV infection imported to Marseilles, France, in travelers returning from the Indian Ocean islands. A total of 47 patients have been diagnosed with imported CHIKV infection confirmed by serology, reverse transcription-polymerase chain reaction, and/or viral culture. At the early stage of the disease (within 10 days of the disease onset), fever was present in 45 of 47 patients. A rash was present in the first week in 25 cases. All patients suffered with arthritis. The most frequently affected joints were fingers, wrists, toes, and ankles. Eight patients were hospitalized during the acute stage, including 2 severe life-threatening cases. A total of 38 patients remained symptomatic after the tenth day with chronic peripheral rheumatism, characterized by severe joint pain and multiple tenosynovitis, with a dramatically limited ability to ambulate and carry out activities in daily life. Three patients were hospitalized at this stage for severe persistent handicap. Follow-up demonstrated slow improvement in joint pain and stiffness despite symptomatic treatment, mainly antiinflammatory and analgesic drugs. In the current series we describe 2 stages of the disease, an initial severe febrile and eruptive polyarthritis, followed by disabling peripheral rheumatism that can persist for months. We point out the possibility of transitory peripheral vascular disorders during the second stage and the occasional benefit of short-term corticosteroids. As CHIKV could spread throughout the world, all physicians should be prepared to encounter this arboviral infection.

[Marseilles, the Indian Ocean and Chikungunya virus]. / Marseille, l'Océan indien et le virus Chikungunya.

In recent decades Marseilles, through immigration, has become the largest Comorian city outside the archipelago. It is also home to a faculty of medicine that has made infectious diseases one of its fields of excellence. During the last two years, Marseilles has spearheaded the metropolitan French response to the Chikungunya crisis in the Indian Ocean region, and especially in the Reunion Island and Mayotte. Laveran military teaching hospital (Hôpital d'instruction des armées, HIA) has managed one of the largest metropolitan cohorts. Its teams have also reported the broad clinical spectrum of the disease in its later stages, and especially the high incidence of incapacitating tenosynovitis and distal arthritis, as well as the occurrence of a transient acrosyndrome during the second and third months in nearly one-quarter of patients. Importantly, they have also identified a mixed cryoglobulin in more than 90% of patients, the level of which matches clinical symptoms and is sensitive to systemic steroid therapy. This discovery opens the way to a better understanding of the pathophysiology of this viral disease. The Tropical Virology laboratory of the Tropical Medicine Institute of the Army health service (IMTSSA), which has close links with the national references center (CNRS) arbovirus laboratory, has developed new diagnostic tools, notably based on RT-PCR. Together with national reference center (CNRS), the laboratory produces and supplies antigens for Chikungunya serological tests in metropolitan France and overseas. It has taken into account the presence of cryoglobulins, which can lead to false-negative results in infected patients, and has considerably increased the diagnostic yield of serological techniques. The laboratory's fundamental research focuses on genomic characterization of viral variants isolated from humans and from the vector, and also on viral protease expression, for functional studies and antiviral candidate drug selection. The laboratory also collaborates with clinical teams in Reunion and metropolitan France working on humoral and cellular immune responses and on the different clinical forms of the disease. The Epidemiology and Public Health Department of IMTSSA conducted an epidemiological study of all gendarmes working in Reunion at the end of the epidemic (June 2006). This study, done in partnership with the tropical virology laboratory and CNRS, is helping to complete the clinical description of the epidemic, in an unbiased population. In 2007, it will form the basis for a prospective cohort study in which these patients will be monitored for several years to better document the chronic phase of the disease in a population with excellent healthcare access. Finally, the department has provided the civil authorities with advice and support in disease-control operations in Reunion. Communication played an important role in the management of this crisis, showing how crucial it now is for healthcare professionals to develop relevant skills. The Army Health Service in Maarseilles was never isolated from its university partners, as witnessed by clinical collaboration between Laveran HIA and CHU Nord (a Marseilles teaching hospital) and by virological cooperation between the IMTSSA and Etablissement français du sang (EFS) laboratories. This experience is highly encouraging with respect to the creation in Marseilles of a healthcare research network (RTRS) devoted to tropical and emerging infectious diseases.