Survival of Phortica variegata experimentally and naturally infected with Thelazia callipaeda.

Knowledge of the effects that Thelazia callipaeda (Spirurida, Thelaziidae) infection has on the survival of its vector Phortica variegata (Drosophilidae, Steganinae) is scarce. The present study aimed to: (a) assess the rate of infection between experimentally infected (EI) and not experimentally infected (NEI) flies and (b) determine how T. callipaeda infection may affect the survival of P. variegata. In addition, fat composition was evaluated in flies that died during overwintering. Molecular analysis showed that T. callipaeda prevalence in flies that died before experimental infection, plus those from the NEI group, is 0.75% (i.e. 11 out of 1462 individuals). The EI group showed a significantly higher positivity to T. callipaeda (i.e. 51 out of 682 individuals; 7.48%) compared with the NEI group (i.e. 9 out of 750 individuals; 1.2%). Thelazia callipaeda DNA was detected until 147 days after experimental infection. This demonstrates that larvae of this eyeworm may survive in the fly for a significant period of the winter. Fat composition analysis showed that flies produced more unsaturated than saturated fatty acids during diapause, probably because unsaturated fatty acids remain in a liquid state at lower temperatures, providing anti-freeze properties to survive winter.

AMPK is activated early in cerebellar granule cells undergoing apoptosis and influences VADC1 phosphorylation status and activity.

The neurodegeneration of cerebellar granule cells, after low potassium induced apoptosis, is known to be temporally divided into an early and a late phase. Voltage-dependent anion channel-1 (VDAC1) protein, changing from the closed inactive state to the active open state, is central to the switch between the early and late phase. It is also known that: (i) VDAC1 can undergo phosphorylation events and (ii) AMP-activated protein kinase (AMPK), the sensor of cellular stress, may have a role in neuronal homeostasis. In the view of this, the involvement of AMPK activation and its correlation with VDAC1 status and activity has been investigated in the course of cerebellar granule cells apoptosis. The results reported in this study show that an increased level of the phosphorylated, active, isoform of AMPK occurs in the early phase, peaks at 3 h and guarantees an increase in the phosphorylation status of VDCA1, resulting in a reduced activity of this latter. However this situation is transient in nature, since, in the late phase, AMPK activation decreases as well as the level of phosphorylated VDAC1. In a less phosphorylated status, VDAC1 fully recovers its gating activity and drives cells along the death route.

Score for pulmonary tuberculosis in patients with clinical presumption of tuberculosis in a low-prevalence area.

OBJECTIVES: To develop a diagnostic predictive model for the identification of patients with presumptive pulmonary tuberculosis (PTB) at high risk for active disease and those requiring nucleic acid amplification (NAAT) testing and/or preventive respiratory isolation in low-incidence, high-income countries. DESIGN: A 1:1 case-control study was conducted in consecutive immunocompetent patients with presumed PTB hospitalised between 2009 and 2012 in Paris, France. Cases were defined as individuals with culture-confirmed PTB, regardless of smear result. Those with presumed PTB and three smear- and culture-negative samples were selected as controls. A score was derived using conditional logistic regression. Internal validity of the score was assessed using the bootstrap method. RESULTS: A total of 354 patients were included in the analysis (177 cases, 177 controls). Among the 177 cases, 74 (42%) were smear-negative but culture-positive. Factors independently associated with PTB were age <50 years (adjusted OR [aOR] 4.7, 95%CI 1.8-12), diabetes (aOR 3.2, 95%CI 1.1-9.8), absence of cough with or without sputum (aOR 3.7, 95%CI 1.7-8.3), fever >15 days (aOR 3.5, 95%CI 1.3-9.5), apical infiltration without cavity (aOR 3.4, 95%CI 1.4-8.5) and cavitation or miliary pattern (aOR 19.7, 95%CI 7.6-51.1). Score C-index was 0.84 (95%CI 0.79-0.88). Calibration for the overall population (P = 0.770) and in smear-negative patients (P = 0.980) was appropriate. A score of 3.3 had 90% sensitivity, 50% specificity and 79% (IQR 28-95) median probability of PTB. CONCLUSIONS: This score could be used to build an algorithm to determine the need for respiratory isolation and/or NAAT use in PTB disease.

Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae.

Emergence of resistant Enterobacteriaceae in the intestinal microbiota during antibiotic treatment is well documented but its early dynamic is not. Here, we compared the densities of total Enterobacteriaceae and relative abundance (RA) of quinolone-resistant Enterobacteriaceae (QRE) in the first stool passed by patients who had a short exposure to levofloxacin (levofloxacin, n=12) or not (control, n=8). Mean densities (SD) (log CFU/g stool) of total Enterobacteriaceae were lower in the levofloxacin group than in the control group-3.4 (1.6) versus 6.7 (1.7), respectively, p <0.001. Conversely, mean RA (SD) of QRE was significantly higher in the levofloxacin group than in the control group-49.7% (23.4) versus 0.1% (3.2), respectively, p <0.05). In conclusion, even a short exposure to levofloxacin has a profound impact on the densities of total Enterobacteriaceae and the QRE-RA.

Deliberate drug poisonings admitted to an emergency department in Paris area - a descriptive study and assessment of risk factors for intensive care admission.

OBJECTIVE: Each year, approximately 165,000 poisonings are managed in the emergency departments (ED) in France. We performed a descriptive analysis of self-poisoned patients admitted to a university hospital ED in the Paris metropolitan area (France) aimed at investigating their outcome and the risk factors for transfer to the intensive care unit (ICU). PATIENTS AND METHODS: We retrospectively reviewed patients' records and performed multivariate logistic regression analysis to identify risk factors for ICU admission. RESULTS: During 4 years, 882 self-poisoned patients (median age, 38 years [IQR, 26-47]; sex-ratio, 1M/3F) were admitted to the ED, representing 0.7% of all referred patients. Poisonings mainly resulted from multidrug exposures (53%), including benzodiazepines (78%), serotonin reuptake inhibitors (17%), acetaminophen (13%), antipsychotics (9.5%), imidazopyridines (9.5%), antihypertensive drugs (3%), and polycyclic antidepressants (1.3%). Ethanol was involved in 20% of the exposures. Patients were briefly (<24h) monitored in the ED (55%), transferred to the psychiatric department (30%), medical ward (2%) or ICU (6%), and took an irregular discharge (7%). Among the patients transferred to the ICU, 25% were mechanically ventilated and only one died. Risk factors for ICU admission included antihypertensive (Odds ratio (OR), 40.6; 95%-confidence interval (CI), 7.5-221.9) or antipsychotic drug ingestion (OR, 5.3; CI, 2.0-14.4), male gender (OR, 3.3; CI, 1.30-8.8), and consciousness impairment (OR, 2.1; CI, 1.8-2.5 per point lost in Glasgow coma score). CONCLUSIONS: Deliberate drug exposure represents a frequent cause of ED admission. Psychotropic drugs are most commonly involved. Transfer to the ICU is rare and predicted by male gender, drug class, and coma depth.

Thioredoxin/thioredoxin reductase system involvement in cerebellar granule cell apoptosis.

The involvement of thioredoxin/thioredoxin reductase system has been investigated in cerebellar granule cells (CGCs), a cellular system in which neurons are induced in apoptosis by the physiological stimulus of lowering extracellular potassium. Clarifying the sequence of events that occur during apoptosis is a critical issue as it can lead to the identification of those key events that, if blocked, can slow down or reverse the death process. The results reported in this work show that TrxR is involved in the early phase of CGC apoptosis with an increase in activity that coincides with the increased expression of the TrxR1 isoform and guarantees the maintenance of adequate level of Trx in its reduced, active form. However, in late apoptosis, when about 50 % of cells are dead, partial proteolysis of TrxR1 by calpain occurs and the reduction of TrxR1 mRNA, together with the overall decrease in TrxR activity, contribute to increase the levels of the oxidized form of Trx. When the reduced form of Trx is externally added to apoptotic cultures, a significant reduction in cell death is achieved confirming that a well-functioning thioredoxin/thioredoxin reductase system is required for survival of CGCs.

Persistent organic pollutants (PCBs and DDTs) in small size specimens of bluefin tuna (Thunnus thynnus) from the Mediterranean Sea (Ionian Sea).

The concentration levels and pattern distribution of polychlorinated biphenyls (PCBs) and organochlorine pesticides (DDTs), were investigated in liver of small size specimens of bluefin tuna (Thunnus thynnus) from Mediterranean Sea (Ionian Sea). PCB concentrations (average: 526 ng g(-1) lipid wt) were comparable with DDT levels (average: 435 ng g(-1) lipid wt). The specific analysis of PCB congeners revealed a profile dominated by hexa-, penta- and heptachlorinated congeners, while among DDTs, the compounds with the higher concentration was p,p'-DDE, constituting 91.9% of the total DDT. The total 2,3,7,8-TCDD toxic equivalent (TEQs) of coplanar PCBs, including mono- and non-ortho congeners, was 0.55 pg g(-1) wet weight with. The congeners with highest TEQs values were non-ortho congeners followed by mono-ortho ones.

[Medicinal iatrogenics in hospitals. A survey on a given day]. / Iatrogénie médicamenteuse à l'hôpital. Enquête un jour donné.

OBJECTIVE: Medicinal iatrogenics are responsible for hospital admissions but also occur in hospitals. In view of the lack of knowledge, prevalence and nature of the adverse drug-related events (ADE) in the Bichat-Claude Bernard hospital group in Paris, and because of the potential severity of the latter, the Local drug committee has decided to develop a policy to manage these risks. METHOD: The first stage consisted in a transversal study on a given day in the departments in which patients are hospitalised for more than 24 hours, in order to assess the prevalence, severity and preventability of ADE and to search for factors of risk. RESULTS: 107 ADE were observed in 89 patients on the day of the survey (9.9% global prevalence of ADE [CI 95%: 8.8% - 11.0%]). Among the latter, 57 patients had exhibited at least one adverse event during their hospitalisation, i.e., a prevalence of 6.3% ([CI 95%: 4.7% - 7.9%] ). Two thirds of these patients were hospitalised in medical departments. These nosocomial ADE (nosocomial adverse drug events) were serious or severe in 73% of cases and 25% could have been avoided. The only clearly identified risk factor was the number of drugs prescribed. CONCLUSION: This review has drawn the attention of the medical and paramedical community to the need to define vigilance markers, and has provided some elements of response that should be further completed by a prospective cohort study.

[Anti-HIV chemoprophylaxis for blood-exposure accidents]. / Chimioprophylaxie anti-VIH des accidents exposant au sang.

Chemoprophylaxis against HIV after accidental blood exposures represents a new indication for antiretroviral drugs. Efficacy has been suggested by the results of a case-control study in health care workers and the reduction of mother to infant transmission of HIV with zidovudine. The post-exposure treatment should be given as soon as possible, and in the latest at 48 hours. National guidelines recommend a triple therapy with or without protease inhibitor, adapted to the source patient. The evaluation of efficacy needs a standardized follow-up.

[Development of a predictive model for respiratory isolation of patients suspected of having pulmonary tuberculosis]. / Proposition d'un score décisionnel d'isolement respiratoire précoce des patients suspects de tuberculose pulmonaire.

INTRODUCTION: As numerous nosocomial outbreaks of pulmonary tuberculosis have been reported during the last two decades, prompt identification and effective isolation of contagious patients should be made a priority in tuberculosis control policies. There is a need to develop a predictive model which would allow prompt recognition and isolation of smear-positive patients. CURRENT KNOWLEDGE AND KEY POINTS: Various authors have attempted to improve the respiratory isolation policies for patients suspected of having pulmonary tuberculosis. A French multicenter prospective study of 211 patients suspected of having pulmonary tuberculosis established that: 1) the current respiratory isolation policy of suspected pulmonary tuberculosis needs improvement (sensitivity = 71.4%; i.e., 28.6% of smear-positive patients are admitted without isolation) and 2) better interpretation of clinical and radiological data available on patient admission could improve the adequacy of respiratory isolation. Univariate analysis showed that predictive factors of pulmonary tuberculosis were chest X-rays (P < 0.00001), symptoms (P = 0.0004), age (mean: 40.8 years for TB vs. 47.5 for non-TB, P = 0.04), HIV infection (10.6% vs. 28.7%, P = 0.01), immigrant (72% vs. 55%, P = 0.03) and BCG status (P = 0.025), while multivariate analysis demonstrated that chest X-ray pattern (P < 0.00001), HIV infection (P = 0.002) and symptoms (P = 0.009) were independent predictive factors. FUTURE PROSPECTS AND PROJECTS: From these data, a model was proposed and evaluated in the derivation cohort using the receiver operating characteristics (ROC) curve. We retrospectively studied the predictive model in two populations different from the one from which it was derived. The model would have improved sensitivity of the respiratory isolation policy from 71.4% (current respiratory isolation policy) to 82.4% and 91.1%, respectively. Prospective, multicenter studies are requested to establish the value of such a predictive model in improving the respiratory isolation policy for patients suspected of having pulmonary tuberculosis.

Cadmium-dependent enzyme activity alteration is not imputable to lipid peroxidation.

The effect of cadmium on the liver-specific activities of NADPH-cytochrome P450 reductase (CPR), malic dehydrogenase (MDH), glyceraldehyde-3-phosphate dehydrogenase (GADPH), and sorbitol dehydrogenase (SDH) was assessed 6, 24, and 48 h after administration of the metal to rats (2.5 mg/kg of body weight, as CdCl2, single ip injection). CPR specific activity increased after 6 h and afterward decreased significantly, while MDH specific activity increased up to 24 h and then remained unchanged. Both SDH and GADPH specific activities reduced after 6 h, the former only a little but the latter much more, and after 24 and 48 h were strongly inhibited. In vitro experiments, by incubating rat liver microsomes, mitochondria, or cytosol with CdCl2 in the pH range 6.0-8.0, excluded cadmium-induced lipid peroxidation as the cause of the reduction in enzyme activity. In addition, from these experiments, we obtained indications on the type of interactions between cadmium and the enzymes studied. In the case of CPR, the inhibitory effect is probably due to Cd2+ binding to the histidine residue of the apoenzyme, which, at physiological pH, acts as a nucleophilic group. In vitro, mitochondrial MDH was not significantly affected by cadmium at any pH, indicating that this enzyme is probably not involved in the decrease in mitochondrial respiration caused by this metal. As for GADPH specific activity, its inhibition at pH 7.4 and above is imputable to the binding of cadmium to the SH groups present in the enzyme active site, since in the presence of dithiothreitol this inhibition was removed. SDH was subjected to a dual effect when cytosol was exposed to cadmium. At pH 6.0 and 6.5, its activity was strongly stimulated up to 75 microM CdCl2 while at higher metal concentrations it was reduced. At pH 7.4 and 8.0, a stimulation up to 50 microM CdCl2 occurred but above this concentration, a reduction was found. These data seem to indicate that cadmium can bind to different enzyme sites. One, at low cadmium concentration, stimulates the SDH activity while the other, at higher metal concentrations, substitutes for zinc, thus causing inhibition. This last possibility seems to occur in vivo essentially at least 24 h after intoxication. The cadmium-induced alterations of the investigated enzymes are discussed in terms of the metabolic disorders produced which are responsible for several pathological conditions.

The validity of medical history, classic symptoms, and chest radiographs in predicting pulmonary tuberculosis: derivation of a pulmonary tuberculosis prediction model.

STUDY OBJECTIVE: To improve the respiratory isolation policy for patients with suspected pulmonary tuberculosis (TB). DESIGN: Prospective, descriptive, French multicenter study. SETTING: Emergence of nosocomial outbreaks of TB. PATIENTS: All consecutive patients admitted with suspicion of pulmonary TB. MEASUREMENTS AND RESULTS: Medical history, social factors, symptoms, and chest radiograph (CXR) pattern (symptoms and CXR both scored as typical of pulmonary TB, compatible, negative, or atypical) were obtained on admission. Serial morning sputa were collected. Of the 211 patients, 47 (22.3%) had culture-proven pulmonary TB, including 31 (14.7%) with a positive smear. Mean age was 46.2 years; 52 patients were HIV positive (24.6%). The sensitivity of the respiratory isolation policy was 71.4%, specificity was 51.7%, negative predictive value (NPV) was 88.2%, and positive predictive value (PPV) was 26.3%. On univariate analysis, predictive factors of culture-proven pulmonary TB were CXR (p < 0.00001), symptoms (p = 0.0004), age (mean, 40.8 years for TB patients vs 47.5 years for non-TB patients; p = 0.04), absence of HIV infection (89.4% vs 71.3%; p = 0.01), immigrant status (72% vs 55%; p = 0.03), and bacillus Calmette-Guérin status (p = 0.025). On multivariate analysis, CXR pattern (p < 0.00001), HIV infection (p = 0.002), and symptoms (p = 0.009) remained independently predictive. Based on these data, a model was proposed using a receiver operating characteristics curve. In the derivation cohort, the sensitivity and NPV of the model in detecting smear-positive pulmonary TB would have been 100%. The specificity and PPV would have been 48.4% and 25%, respectively. The model performed less well when evaluated on two retrospective groups, but its sensitivity remained above that of the current respiratory isolation policy (91.1% and 82.4% for the retrospective groups vs 71.1% for the current policy). CONCLUSIONS: Improved interpretation of clinical and radiologic data available on patient admission could improve adequacy of respiratory isolation. A prediction model is proposed.

[Invasive pulmonary aspergillosis in AIDS]. / Aspergilloses pulmonaires invasives au cours du SIDA.

Risk factor for invasive pulmonary aspergillosis in HIV-negative patients include neutropenia, corticosteroid therapy, and chemotherapy. Corresponding risk factors in HIV-positive patients have not yet been reported. A case-control study was conducted at the Bichat-Claude Bernard Teaching Hospital, Paris, France, between 1991 and 1996. Eight cases were identified. In three cases, the diagnosis was documented histologically. Of the remaining five patients, four had a de novo lung cavity with a positive bronchoscopy sample, and one had a pulmonary infiltrate with a positive bronchoscopy sample in the absence of any other potential pathogen. Each case was matched with three controls who were admitted during the same period and had CD4 counts lower than 50/mm3. Median age was 38.1 years in the cases and 38.4 years in the controls. Median CD4 counts were 12.5 +/- 19.2 in the cases versus 19.3 +/- 16.3 in the controls (P = 0.14). No case-control differences were found for AIDS duration, neutrophil counts at diagnosis or during the previous six months, history of corticosteroid therapy or chemotherapy, or number of previous opportunistic infections. Cases were more likely than controls to have a preexisting lung cavity (3/8 versus 0/24; P = 0.01) and had spent more time in the hospital during the previous year (7 +/- 4.5 versus 2.8 +/- 3.2 weeks; P = 0.02). These data do not support a role for neutropenia or immunosuppressive treatments as risk factors for invasive aspergillosis in AIDS. They suggest that AIDS patients with a lung cavity or frequent hospital stays are at increased risk for invasive aspergillosis.

[Cutaneous manifestations during disseminated trichosporonosis in an AIDS patient]. / Manifestations cutanées au cours d'une trichosporonose disséminée chez un malade sidéen.

BACKGROUND: Trichosporon beigelii, causal agent of white piedra can cause disseminated infection in immunodepressed subjects. Systemic infections due to this pathogen have been reported mainly in neutropenic patients and rarely in AIDS patients. CASE REPORT: A 36-year-old HIV+ man from Senegal was hospitalized for fever and meningoencephalitis associated with skin lesions. T. beigelii was isolated from skin biopsies and cerebrospinal fluid cultures. The patients was treated with amphotericin B with regression of the skin lesions. The diagnosis of disseminated T. beigelii infection was retained. DISCUSSION: Disseminated T. beigelii infections are known to occur in immunodepressed subjects, especially in case of neutropenia. In our patient, the presence of two proven localizations (meninges and skin) and the favorable outcome with amphotericin B favored disseminated infection. The good response to treatment can probably be explained by the absence of neutropenia. Skin lesions are frequent, usually occurring as disseminated papulae or purpural nodules. Pathology examination and skin biopsy culture can provide rapid diagnosis allowing appropriate treatment.

Predictors of short- and long-term survival in HIV-infected patients admitted to the ICU.

STUDY OBJECTIVES: To evaluate the prognosis of HIV-infected patients admitted to ICUs and to identify factors predictive of short- and long-term survival. DESIGN: A prospective study from January 1, 1990, to December 31, 1992, including all consecutive HIV-infected patients admitted to our ICU for the first time. ICU survivors were followed up until January 1, 1994. SETTING: An 18-bed infectious diseases ICU in a 1,300-bed university hospital in Paris. PATIENTS: Four hundred twenty-one HIV-related admissions were recorded during the study period (33.5% of 1,258 admissions to ICU); 354 HIV-infected patients were first ICU admissions and were analyzed. MEASUREMENTS AND RESULTS: Predictive factors on univariate and multivariate analyses (logistic regression and Cox model) for short- and long-term mortality were performed. Respiratory failure was the main cause of admission (49.2%), followed by neurologic disorders (26.8%), sepsis (10.2%), heart failure (4.5%), and miscellaneous disorders (9.3%). For these groups, in-ICU and in-hospital mortality rates were as follows: 16.7% and 33.9%; 23.2% and 41.1%; 38.9% and 58.3%; 25% and 68.8%; and 12.1% and 24.2%, respectively. In-ICU and in-hospital mortality rates were significantly different across the groups (p=0.026 and 0.002, respectively). Multivariate analysis showed that the in-hospital outcome was significantly associated with functional status (p=0.05), time since AIDS diagnosis (p=0.04), HIV disease stage (0.016), simplified acute physiology score (SAPS I) (p=0.06), need for mechanical ventilation (p<0.000001), and its duration (p=0.0001). In the 281 patients who were discharged alive from the ICU, cumulative survival rates were 51%+/-38% at 6 months, 28%+/-38% at 12 months, and 18%+/-30% at 24 months. Median and crude mean+/-SD survival times were 199 days and 316+/-343 days. Multivariate analysis showed that the long-term outcome was significantly associated with functional status (p=0.000001), weight loss (p=0.00001), the CD4 count (p=0.00001), the HIV disease stage (p=0.01), the duration of AIDS (p=0.001), the admission cause group (p=0.03), and the SAPS I at admission (p=0.00001). CONCLUSIONS: The short-term (in-ICU and in-hospital) outcome of HIV-infected patients was mainly related to the severity of the acute illness (SAPS I, cause of admission, need for and duration of mechanical ventilation), and to the preadmission health status, based on functional status and weight loss. Some of these parameters, in particular the SAPS I and preadmission health status, also influenced the long-term outcome. Whereas HIV-related variables had little impact on the in-ICU outcome, they were closely related with the in-hospital outcome and even more strikingly with the long-term outcome. Thus, the life expectancy of HIV-infected patients, which depends primarily on the natural history of the HIV infection, is the most powerful determinant of the long-term prognosis. Our results confirm that ICU support for HIV-infected patients should not be considered futile.

Pulmonary tuberculosis: computed tomography and high-resolution computed tomography patterns in patients who are either HIV-negative or HIV-seropositive.

To compare findings of active pulmonary tuberculosis on computed tomography (CT) and high-resolution computed tomography (HRCT) scans in patients without the human immunodeficiency virus (HIV) and patients with HIV, and to define the spectrum of pulmonary tuberculosis in patients with HIV according to the CD4 T cell status, 76 patients (47 patients without HIV and 29 patients with HIV) with newly diagnosed pulmonary tuberculosis were studied retrospectively. The diagnosis of active pulmonary tuberculosis was based on acid-fast bacilli (AFB) in sputum culture. All patients underwent CT within 1 month of diagnosis. Patients with HIV demonstrated significantly less cavitation and bronchial wall thickening (24% vs. 49% [p < 0.05]; and 14% vs. 45% [p < 0.01], respectively) than the combined group of patients with HIV. Centrilobular nodules were significantly less common in patients without HIV (14% vs. 45%, p < 0.05). Lymphadenopathy with low attenuation centers was significantly less frequent in the patients with HIV (3% vs. 15%, p < 0.05). In patients with HIV, cavitation, lymphadenopathy, as well as the the number of nodules and the number of lobes involved correlated well with the CD4 levels. Two patients with less than 50 CD4 T cells/mm3 had normal chest CT results. Atypical chest CT patterns are frequently encountered in patients with HIV. Knowledge of these CT patterns may assist in the diagnosis and follow-up of patients with HIV with known or suspected pulmonary tuberculosis.