The cyclophilin A-binding loop of the capsid regulates the human TRIM5α sensitivity of nonpandemic HIV-1.

The rather few cases of humans infected by HIV-1 N, O, or P raise the question of their incomplete adaptation to humans. We hypothesized that early postentry restrictions may be relevant for the impaired spread of these HIVs. One of the best-characterized species-specific restriction factors is TRIM5α. HIV-1 M can escape human (hu) TRIM5α restriction by binding cyclophilin A (CYPA, also known as PPIA, peptidylprolyl isomerase A) to the so-called CYPA-binding loop of its capsid protein. How non-M HIV-1s interact with huTRIM5α is ill-defined. By testing full-length reporter viruses (Δ env) of HIV-1 N, O, P, and SIVgor (simian IV of gorillas), we found that in contrast to HIV-1 M, the nonpandemic HIVs and SIVgor showed restriction by huTRIM5α. Work to identify capsid residues that mediate susceptibility to huTRIM5α revealed that residue 88 in the capsid CYPA-binding loop was important for such differences. There, HIV-1 M uses alanine to resist, while non-M HIV-1s have either valine or methionine, which avail them for huTRIM5α. Capsid residue 88 determines the sensitivity to TRIM5α in an unknown way. Molecular simulations indicated that capsid residue 88 can affect trans-to-cis isomerization patterns on the capsids of the viruses we tested. These differential CYPA usages by pandemic and nonpandemic HIV-1 suggest that the enzymatic activity of CYPA on the viral core might be important for its protective function against huTRIM5α.

Pattern and consequences of cardiologic medications management for patients with elevated troponin I upon admission into an intensive care unit not linked to type 1 acute myocardial infarction: A prospective observational cohort study.

OBJECTIVES: No recommendations are currently available to help the clinician with the pharmacological management of intensive care unit (ICU) patients with elevated cardiac troponin (cTn) not linked to type 1 AMI. The aim of this study was to evaluate the pattern of cardiologic medications for patients with elevated cTnI in ICU not link to type 1 AMI and their effects on in-hospital mortality. MATERIAL AND METHODS: A prospective observational cohort study conducted in two ICU units. Patients with increased plasma concentration of cTnI at admission not linked to type 1 AMI were consecutively included. RESULTS: One hundred and ninety of the 835 patients admitted (23%) had an increased plasma concentration of cTnI not related to type 1 AMI. Antiplatelet therapy (AT) and statin were prescribed in 56 (29.5%) and 50 (26.3%) of patients, respectively. Others cardiologic medications were prescribed in less than 5% of all cases and were considered as contraindicated in more than 50% of cases. Antiplatelet therapy was the only cardiologic treatment associated with reduction of in-hospital mortality following uni- and multivariate analysis. The death rate was 23% and 40% in these patients treated with and without AT, respectively (aOR=0.39 [95% CI: 0.15-0.97]). CONCLUSIONS: Statin and AT were frequently prescribed to patients with a cTnI elevation not linked to type 1 AMI. This study suggests that AT in patients with an increased plasma concentration of cTnI, not related to type 1 AMI in ICU, could reduce in-hospital mortality.

A study to evaluate the first dose of gentamicin needed to achieve a peak plasma concentration of 30 mg/l in patients hospitalized for severe sepsis.

Previous studies have shown that the high dose of gentamicin (8 mg/kg) rarely achieves the desired peak plasma concentration (Cmax) of ≥30 mg/l in patients with severe sepsis or septic shock. The aim of this study was to determine the first dose of gentamicin needed to achieve a Cmax ≥ 30 mg/l. We conducted a prospective observational cohort study in one intensive care unit. All consecutive patients hospitalized for severe sepsis or septic shock and treated with a first dose of gentamicin >6 mg/kg were evaluated. During the study period, 15 of the 57 patients (26.3 %) treated with gentamicin had a Cmax ≥ 30 mg/l. The median dose of gentamicin administered was 8.9 [7.8-9.9] mg/kg. Independent factors in the multivariate analysis associated with a Cmax ≥ 30 mg/l were higher body mass index (per kg/m(2) increment) (OR: 1.173, 95%CI: 1.015-1.356, P = 0.03) and higher first dose of gentamicin (per mg/kg increment) (OR: 2.343, 95%CI: 1.346-4.08, P = 0.003). The optimal first dose to achieve a Cmax ≥ 30 mg/l was 11 mg/kg, with a specificity and a sensitivity of 100 % and 53.3 % respectively. These results suggest that a first dose of gentamicin >11 mg/kg is needed to achieve a Cmax ≥ 30 mg/l in most patients.

Epidemiology and risk factors of multidrug-resistant bacteria in respiratory samples after lung transplantation.

BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing concern worldwide. The aim of this study was to describe the epidemiology and risk factors of MDR bacteria detected in respiratory invasive samples during hospitalization in the intensive care unit (ICU) after lung transplantation (LT). METHODS: This study was based on a retrospective analysis of 176 patients hospitalized in the ICU after LT in 2006-2012. Respiratory invasive samples were performed according to a routine protocol. MDR pathogens were defined according to in vitro susceptibility tests. RESULTS: A total of 1176 bacteria were cultured. Susceptibility testing was performed on 1046 strains and 404 (39%) MDR were detected in 90 (51%) patients. Pseudomonas aeruginosa, coagulase-negative staphylococci, and Enterobacteriaceae (mainly Enterobacter species) were the most common MDR pathogens. On multivariate analysis, an ICU stay >14 days, presence of a tracheostomy, and previous exposure to broad-spectrum antibiotics were associated with MDR acquisition (odds ratio [OR] 3.7; 95% confidence interval [1.69-8.12]; OR 3.28 [1.05-10.28]; and OR 2.25 [1.17-4.34], respectively). We consistently observed an increasing emergence of resistance to several antibiotics, from week 1 to week 4 of ICU hospitalization: for ticarcillin, piperacillin-tazobactam, ceftazidime, imipenem/cilastatin, amikacin, and ciprofloxacin in P. aeruginosa; and for piperacillin-tazobactam, cefepime, and amikacin in Enterobacteriaceae. CONCLUSION: A large proportion of MDR bacteria are detected on respiratory invasive samples in LT patients, and the risk of their emergence is mainly determined by the previous exposure to broad-spectrum antibiotics and the length of ICU stay. Adequate treatment requires broad-spectrum empiric antibiotic therapy.

Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation.

Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence-based dosing guidelines for ECMO patients.

Apoptosis in gingival overgrowth tissues.

Variations in the balance between cell proliferation and apoptosis could contribute to the etiology of gingival overgrowth. The aim of this study was to test the hypothesis that, in fibrotic gingival lesions, fibroblast proliferation is stimulated and apoptosis is decreased. Apoptotic index, caspase 3 expression, the proliferative index, FOXO1 expression, and histological inflammation were measured in situ. Analysis of data showed that apoptosis decreased in all forms of gingival overgrowth examined (p < 0.05), and inflammation caused a small but significant increase compared with non-inflamed tissues (p < 0.05). The greatest decrease of apoptosis occurred in the most fibrotic tissues. Cell proliferation was elevated in all forms of gingival overgrowth tested, independent of inflammation (p < 0.05). To identify potential mechanisms of transcriptional regulation of apoptosis, we assessed FOXO1 and caspase 3 expression levels and found them to correlate well with diminished apoptosis. Analysis of data suggests that increased fibroblast proliferation and a simultaneous decrease in apoptosis contribute to gingival overgrowth.

Elevated plasma pancreatic enzyme concentrations after Roux-en-Y gastric bypass may indicate closed loop obstruction.

Laparoscopic Roux-en-Y gastric bypass is one of the most commonly performed bariatric procedures and most patients are women of reproductive age. Consequently, general surgeons and obstetricians need to be aware that these patients are at risk of bariatric specific surgical complications during their pregnancy. We report a case involving a 32-year-old woman who had undergone Roux-en-Y gastric bypass surgery 2 years previously. She presented at 25 weeks of gestation with a closed loop obstruction due to a retrograde jejunojejunal intussusception that was initially misdiagnosed as acute pancreatitis.

Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study.

OBJECTIVE: To study the effect of the levorotatory form of 5-hydroxytryptophan on the cerebellar symptoms of Friedreich's ataxia. DESIGN: Cooperative double-blind study of the levorotatory form of 5-hydroxytryptophan vs placebo. SETTING: Twelve centers in research hospitals. PATIENTS: Twenty-six patients were included; 19 completed the study (mean +/- SD age of patients, 25.9 +/- 8.1 years). Of these 19 patients, eight were treated with placebo and 11 were treated with the drug. MAIN OUTCOME MEASURES: A semiquantitative scale for kinetic and static ("postural") cerebellar functions and quantitative measurements of time in standard tests that evaluated stance, speech, writing, and drawing. RESULTS: In the active treatment group, a significant decrease of the kinetic score was observed (P = .03), indicating an improvement in coordination. CONCLUSIONS: These results demonstrated that the levorotatory form of 5-hydroxytryptophan is able to modify significantly the cerebellar symptoms in patients with Friedreich's ataxia. However, the effect is only partial and not clinically major.

The pulmonary air-blood barrier of human shock lungs (a clinical, ultrastructural and morphometric study).

Interstitial edema in the alveolar septa is the first morphologically recognisable change to be observed in cases of shock. It is brought about by the altered function of the membranes of the damaged epithelium and endothelium in the alveolar wall. At the same time there is an impairment of gaseous exchange, which is rendered more difficult by the exudative process in the interstitium. Pari passu with these events there is injury to the cells of both the alveolar epithelium and the alveolar capillary endothelium. Both these processes are still reversible. The point of irreversibility appears to be reached--so far as time is concerned--at the end of the first week, after which the injurious effects on the cell are established, since the thin alveolar wall necessary for the exchange of gases becomes overgrown with bulky alveocytes (Tpye II), and the fibroblasts in thealveolar interstitium push the capillaries away from the surface of the alveolus. In most of the advanced cases of shock this process of thickening of the alveolar wall exceeds the critical value, and respiratory exchange is so impaired that satisfactory functioning of the lungs is no longer possible.

[Palinacousis with hemianacusia caused by left temporal lesion]. / Palinacousie avec hémianacousie par lésion temporale gauche.

Palinacousis (auditory perseveration) is reported in a 78-year-old patient with a left temporo parietal astrocytoma. The patient complained of "echoing voice" in his right ear. Palinacousis was associated with sensitive partial seizures. Neuropsychological investigations revealed hemianacusia with normal performance for phonological discrimination and verbal repetition. We suggest that these preserved abilities allowed emergence of palinacousis.

[Malignant degeneration of epidermal cyst of the posterior cranial fossa. Diagnostic value of magnetic resonance imaging]. / Dégénérescence maligne d'un kyste épidermoïde de la fosse postérieure. Intérêt diagnostique de l'imagerie par résonance magnétique.

A 72 year-old woman presented with a rapidly evolving left cerebellopontine angle syndrome secondary to a squamous cell carcinoma developed in an epidermoid cyst. The value and the results of magnetic resonance imaging are discussed.

[Hematoma of the pyramidal muscle. A complication of anticoagulant treatment]. / Hématome du muscle pyramidal. Complication d'un traitement anti-coagulant.

A patient developed a hematoma of the pyramidal muscle as a complication of anticoagulant treatment. The lesion provoked an entrapment neuropathy due to the compression between the muscle and the iliac spine of the great sciatic, inferior gluteal and pudendal nerves. Hyperalgic paralysis of the leg and buttock was associated with bladder sphincter disorders and impotence, a remarkable finding in view of the unilateral disturbance in nervous control. Pain, and urinary and sexual disorders were reversed dramatically by an early neurolysis. A CT scan enables the identification of the lesion.

[Dura mater arteriovenous fistula and lateral sinus occlusion]. / Fistule artério-veineuse dure-mérienne et occlusion du sinus latéral.

It is rare to find an arteriovenous fistula of the dura mater associated with a venous sinus occlusion, but this may provide evidence of an etiology. In the case reported, the malformation was probably of congenital origin, the sinus thrombosis having occurred secondarily to the venous stasis adjacent to the fistula.

[Intermittent sea-saw nystagmus successfully treated with clonazepam]. / Abolition par le clonazépam d'un nystagmus en bascule intermittent.

See-saw nystagmus is a pendular nystagmus with two distinct components: a conjugate torsional component and a disjonctive vertical component. The acquired form of nystagmus is usually seen with parasellar mass and less frequently in head injury or brainstem infarction. Almost all patients with parasellar mass or head injury have associated bitemporal hemianopia. We report the case of a 27-year-old man who developed intermittent daily oscillopsia five years after a severe head injury. On neurological examination, the patient showed a congenital left eye divergence with left eye convergence paresis, an anosmia, a right optic atrophy and a bitemporal hemianopia. Visual acuity was 7/10 and 3/10 for the right and left eyes. The rest of the neurological examination was unremarkable. Electroencephalogram during oscillopsia was normal. MRI revealed bilateral orbito-frontal low signal intensity on T1 weighted images. The brainstem, the diencephalon and the ventricular system appeared to be intact. Eye movement recordings exhibited intermittent see-saw nystagmus. Clonazepam treatment resolved the see-saw nystagmus. Slowly withdrawal of clonazepam was done without return of the see-saw nystagmus.

[Late neurologic complications of galactosemia: study of 3 cases]. / Complications neurologiques tardives de la galactosémie: étude de trois cas.

Galactosemia is an autosomal recessive, inborn error of galactose metabolism due to the deficiency of galactose-I-phosphate uridyl transferase. Late-onset neurologic complications may develop despite Galactose restriction. Three adult patients are reported. They suffered from mental retardation. Two of them developed progressive cerebellar ataxia, spastic gait and postural tremor. The magnetic resonance imaging revealed moderate cortical atrophy, multifocal areas of increased signal in the periventricular white matter on T2-weighted images, and in one case, abnormal myelination. The Fluoro-2-deoxy-D-glucose position emission tomography showed different patterns of regional hypometabolism.

[Saccadic latencies and unilateral spatial neglect caused by parietal lesions]. / Latences saccadiques et négligence spatiale unilatérale par lésion pariétale.

Latencies of lateral visually guided saccades were studied in 12 right handed patients who had unilateral ischaemic lesions involving the parietal lobe. The patients were divided into two groups according to the right or left side of the lesions. The severity of unilateral spatial neglect was assessed. In right parietal lesions, the asymmetry of latencies was related to the presence of unilateral spatial neglect and correlated with ist severity. According to the stimulus condition used, we suggest that the asymmetry of latency is explained in terms of an inability to disengage.

[Continuous partial epilepsy disclosing diabetes mellitus]. / Epilepsie partielle continue révélatrice d'un diabète sucré.

Continuous partial epilepsy (CPE) is characterized by isolated, subintrant clonus focalized to a limited territory with critical focal electroencephalography in a concordant territory. CPE is observed in various cortical lesions but also in disorders of metabolism and notably decompensated diabetes mellitus. We report a case of CPE without focal lesion at MRI which revealed hyperglycaemia without ketosis. The 54-year old female patient was hospitalised for C.P.E.. Early CT and later MRI gave normal results. Biochemistry showed hyperglycaemia without kenoturia, acidosis or hyperosmolality. Insulin therapy rapidly brought glycaemia down to its normal level and the clonsism disappeared. Five months later, the patient had no other seizure and the EEG was normal. Epileptic seizures are frequent in hyperglycaemia without ketosis (25% of the cases) where they are mainly partial and motor (75 to 86% of the cases), rarely associated with a focal lesion (15% of the cases with CT scan). They are rare in patients with ketoacidosis. This apparent protective effect of ketoacidosis may be attributed to an increase of GABA bioavailability consecutive to acidosis. CPE is resistant to antiepileptic treatments. In CPE induced by hyperglycaemia without ketosis normalization of blood glucose level with insulin therapy is concomitant with a rapid cure of epilepsy. Thus glycaemia should be measured in all patients presenting with CPE, the aim being to diagnose hyperglycaemia without ketosis rapidly to avoid hyperosmolality and to prescribe an adequate treatment based exclusively on insulin and rehydration.

[Spontaneous thrombosis of cerebral arteriovenous malformation]. / Thrombose spontanée d'une malformation artério-veineuse cérébrale.

Complete disappearance of a cerebral arteriovenous malformation (AVM), 9 years after its discovery, is reported in a 45-year-old man. This unusual evolution was revealed by the onset of 3 seizures. CT scan and MR imaging eliminated any hemorrhage and carotid angiography showed the spontaneous thrombosis of the whole malformation. The evolution of the MRI signals demonstrates that seizures and the disappearance of the AVM were concomitant. It is suggested that the spontaneous thrombosis of the venous drainage caused the AVM disappearance with cerebral oedema responsible of seizures.

Effect of music on ambulatory surgery patients' preoperative anxiety.

The authors investigated music as a method to reduce ambulatory surgery patients' preoperative anxiety. They assigned 42 patients to either an experimental or a control group and compared the patients' vital signs and self-reports of anxiety, which were measured using the state portion of the State-Trait Anxiety Inventory. The study results indicate that music can be more beneficial than preoperative instruction alone in reducing ambulatory surgery patients' anxiety. Patients who listened to their choice of music before surgery in addition to receiving preoperative instruction had significantly lower heart rates than patients in the control group who received only preoperative instruction. Differences in experimental and control group patients' blood pressure measurements and respiratory rates approached significance. The authors suggest that perioperative nurses offer music as a viable option to reduce anxiety in ambulatory surgery patients who believe music is a method of relaxation.

[Cerebrovascular complication in non-bacterial thrombotic endocarditis. Value of cardiac transesophageal ultrasonography]. / Accident vasculaire cérébral compliquant une endocardite thrombotique non bactérienne. Intérêt de l'échographie cardiaque transoesophagienne.

BACKGROUND: Non-bacterial thrombotic endocarditis in patients with cancer can lead to ischemic stroke. Endocardial vegetations are usually small and may be missed at transthoracic echocardiography. CASE REPORT: Disseminated intravascular coagulation developed in a woman with ischemic stroke. Transthoracic echocardiography was normal. Four days later, transesophageal echocardiography revealed a large mitral vegetation suggesting non-bacterial thrombotic endocarditis. The diagnosis was confirmed at pathology which reported carcinoma of the colon. DISCUSSION: Transthoracic echocardiography is rarely contributed to the diagnosis of thrombotic endocarditis. In our patient transesophageal echocardiography grave the diagnosis before death instead of retrospectively at autopsy as usually occurs, demonstrating the value of transesophageal echocardiography for cancer patients who develop ischemic stroke.