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We report here a case of a random synchronous male breast malignancy in a patient with a known base of tongue malignancy that was incidentally detected on a whole body 18-fluorine deoxyglucose positron emission tomography and computed tomography ((18)F-FDG PET/CT). Patient was referred to us for PET/CT staging and radiotherapy planning for a poorly differentiated squamous cell carcinoma of base of tongue. Histopathologically, the incidentally detected breast lesion was proven to be an invasive ductal carcinoma. (18)F-FDG PET/CT being a whole body imaging modality is known to detect a considerable number of synchronous primaries. Synchronous malignancies in the head and neck area and the upper aerodigestive tract are well established. However, synchronous malignancy in male breast is reportedly uncommon. Our case is unique for the fact that a random synchronous dual malignancy of base of tongue and breast in a male patient was detected during a whole body (18)F-FDG PET/CT imaging.

Aim: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these changes., Methods: Considering that FDG-PET scanning has the ability to show changes in glucose metabolism in the myocardium, we retrospectively analyzed the FDG-PET studies of 18 lymphoma patients treated with adriamycin-based chemotherapy in both the pre- and post-therapy setting. Cardiac contractile parameters such as left ventricular ejection fraction were not available for correlation in all patients due to the short duration and the level of cumulative dose administered in these patients during the time of the follow-up FDG-PET study. The change in myocardial glucose utilization was estimated by change in standard uptake values (SUV) in the myocardium., Results: We observed a significant change in SUVmean values in the myocardium (defined as more than ± 20% change in cardiac SUVmean between pre- and post-chemotherapy PET) in 12 patients, whereas 6 patients did not show any significant cardiac FDG uptake in both pre- and post-therapy PET scans. Patients were divided into three groups based on the changes observed in myocardial tracer uptake on the follow-up (18)F-FDG-PET study. Group A (n = 8): showed an increase in cardiac (18)F-FDG uptake in the post-therapy scan compared to the baseline scan carried out prior to starting adriamycin-based chemotherapy. Group B (n = 6): showed no significant cardiac (18)F-FDG uptake in post-therapy and baseline PET scans, and group C (n = 4): showed a fall in cardiac (18)F-FDG uptake in the post-therapy scan compared to the baseline scan. Mean cumulative adriamycin dose (in mg/m(2)) received during the time of the follow-up FDG-PET study was 256.25, 250 and 137.5, respectively., Conclusion: Our study shows three different trends in the change in myocardial glucose metabolism in patients undergoing adriamycin-based chemotherapy. A further prospective study with prolonged follow-up of ventricular function is warranted to explore the significance of enhanced FDG uptake as a marker of early identification of adriamycin-induced cardiotoxicity.

Objective: HMGB1 concentration is currently regarded as an important biological marker in many inflammation-related conditions. Although ELISA has been proposed as a convenient way to quantify HMGB1 in biological fluids, various molecules have been shown to complex with HMGB1 and may interfere with HMGB1 detection by this technique. We describe here a simple technical improvement that dissociates HMGB1 containing complexes and therefore increases ELISA sensitivity. This procedure was validated in sera from patients with septic shock., Methods: We prepared in vitro complexes containing HMGB1 protein. Recombinant human HMGB1 (rhHMGB1) was incubated in the presence of molecules that are known to form complexes with HMGB1 such as LPS, IL-1β, or a rabbit antiserum directed against HMGB1. Then we tested the capacity of perchloric acid (PCA) to dissociate these complexes by quantifying rhHMGB1 by ELISA immediately or following PCA treatment., Results: We demonstrated for the first time that incubation of rhHMGB1 with, IL-1β, LPS or specific antibodies significantly reduce the amount of protein detected by conventional ELISA (p<0.05). Treating the samples with PCA prior ELISA efficiently reversed this inhibition. As expected, PCA-modified ELISA detected significantly higher amounts of HMGB1 in plasma samples from 40 patients with septic shock compared to conventional ELISA (p=0.0006)., Conclusions: We designed a performing assay that allows the detection of masked and unmasked forms of HMGB1 with a high sensitivity and practicability., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To assess the prevalence and predictive value of natural autoantibodies to high-mobility group box 1 (HMGB1) during sepsis., Methods: Anti-HMGB1 and anti-human serum albumin (HSA) autoantibodies were detected by ELISA in 178 plasma samples longitudinally collected from 40 critically ill patients with septic shock. One hundred thirty-two plasma samples from healthy donors were used as control., Results: IgGs to HMGB1 were detected in 15/40 patients (37.5%). The prevalence of anti-HMGB1 antibodies was significantly higher in the patients who survived (55%) compared to the patients who did not (20%) (p<0.0001). The detection of anti-HMGB1 antibodies during the course of the disease was significantly associated with patient survival (p=0.038). Moreover, there is a progressive and significant emergence of anti-HMGB1 antibodies during the course of the disease, mostly in patients who survived., Conclusions: This study shows that autoantibodies to HMGB1 are produced during sepsis and are associated with a favorable outcome in patients undergoing septic shock., (© Copyright jointly held by Springer and ESICM 2011)

Highly active antiretroviral therapy is associated with carbohydrate metabolic alterations that may lead to diabetes. One consequence of hyperglycemia is the formation of advanced glycation end products (AGEs) that are involved in diabetes complications. We investigated the impact of AGEs on the infection of monocyte-derived dendritic cells (MDDCs) by HIV-1 and the ability of MDDCs to transmit the virus to T cells. We showed that AGEs could inhibit infection of MDDCs with primary R5-tropic HIV-1(Ba-L) by up to 85 ± 9.2% and with primary X4-tropic HIV-1(VN44) by up to 60 ± 8.5%. This inhibitory effect of AGEs was not prevented by a neutralizing anti-receptor for advanced glycation end products (anti-RAGE) Ab, demonstrating a RAGE-independent mechanism. Moreover, AGEs inhibited by 70-80% the transmission in trans of the virus to CD4 T cells. Despite the inhibitory effect of AGEs on both MDDC infection and virus transmission in trans, no inhibition of virus attachment to cell membrane was observed, confirming that attachment and transmission of the virus involve independent mechanisms. The inhibitory effect of AGEs on infection was associated with a RAGE-independent downregulation of CD4 at the cell membrane and by a RAGE-dependent repression of the CXCR4 and CCR5 HIV-1 receptors. AGEs induce the secretion of proinflammatory cytokines IL-6, TNF-α, and IL-12, but not RANTES or MIP-1α, and did not lead to MDDC maturation as demonstrated by the lack of expression of the CD83 molecule. Taken together, our results suggest that AGEs can play an inhibiting role in HIV-1 infection in patients who accumulate circulating AGEs, including patients treated with protease inhibitors that developed diabetes.

Background: High mobility group box 1 protein (HMGB1) is a major endogenous danger signal that triggers inflammation and immunity during septic and aseptic stresses. HMGB1 recently emerged as a key soluble factor in the pathogenesis of various infectious diseases, but nothing is known of its behaviour during herpesvirus infection. We therefore investigated the dynamics and biological effects of HMGB1 during HSV-2 infection of epithelial HEC-1 cells., Methodology/principal Findings: Despite a transcriptional shutdown of HMGB1 gene expression during infection, the intracellular pool of HMGB1 protein remained unaffected, indicating its remarkable stability. However, the dynamics of HMGB1 was deeply modified in infected cells. Whereas viral multiplication was concomitant with apoptosis and HMGB1 retention on chromatin, a subsequent release of HMGB1 was observed in response to HSV-2 mediated necrosis. Importantly, extracellular HMGB1 was biologically active. Indeed, HMGB1-containing supernatants from HSV-2 infected cells induced the migration of fibroblasts from murine or human origin, and reactivated HIV-1 from latently infected T lymphocytes. These effects were specifically linked to HMGB1 since they were blocked by glycyrrhizin or by a neutralizing anti-HMGB1 antibody, and were mediated through TLR2 and the receptor for Advanced Glycation End-products (RAGE). Finally, we show that genital HSV-2 active infections also promote HMGB1 release in vivo, strengthening the clinical relevance of our experimental data., Conclusions: These observations target HMGB1 as an important actor during HSV-2 genital infection, notably in the setting of HSV-HIV co-infection.

The existence of infectious agents smaller than bacteria was demonstrated already near the close of the 19th century by Martinus Beijerinck. After this discovery it took more than 60 years before a resilient definition of viruses could be given and an introduction to modern virology was established. Indeed, the major challenge was to conceive living submicrospic agents exclusively defined in opposition to the bacteriological criteria (non-observable, non-cultivable,). Progresses in biochemistry, electron microscopy, and in control of cell culture techniques have led to the conviction that the viruses were infectious agents entirely original. These last 20 years unrevealed molecular biology as a tool of choice for the discovery of new viral agents and analysis of pathologies of viral etiology., (Copyright © 2009 Elsevier Masson SAS. All rights reserved.)

HMGB1 (High Mobility group box 1) protein was originally identified as a DNA-binding protein that functions as a structural co-factor. Recent works demonstrated that HMGB1 can be released outside the cell, upon immune activation or primary cell necrosis. In the extracellular space, HMGB1 acts as a potent soluble factor that coordinates cellular events that are crucial for the amplification of inflammation, establishment of early immune responses and tissue repair. However, extracellular HMGB1 also acts as a potent pro-inflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders., (Copyright © 2009 Elsevier Masson SAS. All rights reserved.)

A large set of nucleic acid detection methods with good sensitivity and specificity are now available for the detection of pathogens in clinical, food and environmental samples. Given increasing demand, many efforts have been made to combine these methods to assess viability. Genomic DNA PCR amplification has been shown to be inappropriate for distinguishing viable from dead bacteria owing to DNA stability. Many authors have tried to bypass this difficulty by switching to RNA amplification methods such as reverse transcription-PCR and nucleic acid sequence-based amplification. More recently, researchers have developed methods combining specific sample pretreatment with nucleic acid detection methods, notably ethidium or propidium monoazide pretreatment coupled with PCR DNA detection or direct viable count methods and subsequent fluorescent in situ hybridization of 16S rRNA. This review evaluates the performance of these different methods for viability assessment.

A series of "Balanced Catalytic Surfactants" (BCS) [(Cn)2N(C1)2]2MoO4 (n = 8, 9, 10, 12) based on amphiphilic double-tailed quaternary ammonium with molybdate as a counterion has been developed for the dark singlet [4 + 2] cyclooxygenation of organic substrates in three-liquid-phase microemulsion systems. These cationic surfactants form three-liquid-phase microemulsion systems at room temperature in the presence of an appropriate organic solvent and water without addition of any cosurfactant or electrolyte. Comparative peroxidation of rubrene points out the specific advantages of these three-phase media over phase transfer catalysis in two phase systems and on conventional one-phase microemulsions based on sodium molybdate: (i) only three constituents, (ii) low amounts of surfactants, (iii) insensitivity to water dilution, (iv) fast separation of the three phases, (v) straightforward recovery of the product and the surfactant from the oil and microemulsion phases, respectively. The preparative peroxidation of alpha-terpinene and 1,4,5-trimethylnaphtalene was performed in the ternary systems [(C8)2N(C1)2]2MoO4/water/tert-butyl acetate or benzene. The reusability of the catalyst, the catalytic nature of the BCS, and the ability of the systems to oxidize poorly reactive substrates were demonstrated showing the broadness of the applicability of such systems.

Background: Protein HMGB1, an abundant nuclear non-histone protein that interacts with DNA and has an architectural function in chromatin, was strikingly shown some years ago to also possess an extracellular function as an alarmin and a mediator of inflammation. This extracellular function has since been actively studied, both from a fundamental point of view and in relation to the involvement of HMGB1 in inflammatory diseases. A prerequisite for such studies is the ability to detect HMGB1 in blood or other biological fluids and to accurately measure its concentration., Methodology/principal Findings: In addition to classical techniques (western blot, ELISA) that make use of specific anti-HMGB1 antibodies, we present here a new, extremely sensitive technique that is based on the fact that hemicatenated DNA loops (hcDNA) bind HMGB1 with extremely high affinity, higher than the affinity of specific antibodies, similar in that respect to DNA aptamers. DNA-protein complexes formed between HMGB1 and radiolabeled hcDNA are analyzed by electrophoresis on nondenaturing polyacrylamide gels using the band-shift assay method. In addition, using a simple and fast protocol to purify HMGB1 on the basis of its solubility in perchloric acid allowed us to increase the sensitivity by suppressing any nonspecific background. The technique can reliably detect HMGB1 at a concentration of 1 pg per microliter in complex fluids such as serum, and at much lower concentrations in less complex samples. It compares favorably with ELISA in terms of sensitivity and background, and is less prone to interference from masking proteins in serum., Conclusion: The new technique, which illustrates the potential of DNA nanoobjects and aptamers to form high-affinity complexes with selected proteins, should provide a valuable tool to further investigate the extracellular functions of HMGB1 and its involvement in inflammatory pathologies.

Right Hemisphere Damaged Patients (RHDP) with left hemiparesis are known to experience motor programming difficulties and to have poorer functional outcome when compared with Left Hemisphere Damaged Patients (LHDP). The role played by body-related cognitive disorders remains unclear. In this study we investigate whether reproduction of passive meaningless gestures may contribute to a further development of this question. Ten RHDP with neglect, 10 RHDP without neglect, 10 LHDP, and 10 controls were given a battery of tasks requiring reproduction of passive meaningless gestures. The gestures were passively applied by the examiner on either the ipsilesional or the contralesional upper limb of the subject who was asked to reproduce them with his ipsilesional- non-paretic -limb. LHDP performed virtually as well as controls when the influence of deafferentation was controlled. The performance of RHDP with and without neglect did not differ from each other but both groups were significantly impaired when compared with either controls or LHDP, whether the gestures were applied on the contralesional or ipsilesional limb. RHDP performed defectively whether they had closed or open eyes, which tends to indicate a perceptual multimodal integration disorder rather than a modality-related sensory disorder. The left hemisphere is generally considered dominant for deliberate motor control of both sides of the body, not only for symbolic gestures but also for (visual) imitation of meaningless gestures. The results of this study raise the question of why reproduction of meaningless gestures is more impaired for LHDP than RHDP when stimulus presentation is visual and vice versa when stimulation is passively applied upon the subject's body. One reason may be that in visual imitation, the model is given by another person's body, whereas passive gestures, directly applied upon one's body, place demands on perceptual analysis of one's own body experience. These results might give evidence for a disorder of bilateral, perceptual, multimodal integration of knowledge about one's own body in RHDP.

One month outcome after hospitalization was studied in 1695 persons aged 75 and over, living in the community and admitted to acute care medical units: only 9.6% of them were then institutionalized. Returning home requires a high level of independence for feeding, mental status and continence. The level of dependence of institutionalized patients was particularly high for dressing or bathing, technical care, mental status and security. A multivariate analysis showed that the only independent predictors of institutionalization were: sex, living alone, mental status and hospital type. The role played by physical disability must be counterbalanced by the effective physical assistance, brought to the elderly by institutional or informal home care after hospitalization. These results allow early identification of persons at high risk of institutionalization.

The Wolff-Parkinson-White syndrome is usually observed in young people and is much rarer in patients over 50 years old. This fact may be explained by the demise of a certain number of patients before the age of 50 and/or a change in the clinical features of the syndrome with age and/or of the electrophysiological properties of the normal and accessory conduction pathways. To test the latter hypothesis, the clinical and electrophysiological data of 15 patients over 50 years old with the Wolff-Parkinson-White syndrome (Group I) were compared with that of 10 patients under 30 years old with the same syndrome (Group II). The same protocol of electrophysiological investigation was used in both groups of patients. The results showed a significant difference (p < 0.001) between the two groups in the incidence of associated cardiac disease. This was more common in Group I (1 4 out of 15 patients) than in Group II (2 out of 10 patients). The cardiothoracic ratio was significantly higher in Group I (p < 0.01). The two groups also differed in the age at which tachycardia first occured. 9 out of 11 patients in Group I only had symptoms after thirty years. On the other hand, there was no significant difference in the types of tachycardia and the frequency of attacks. There was no significant difference in QRS, PR, AH, HV intervals, in the ventriculo-atrial conduction time and the effective refractory periods of the atrium, right ventricle or atrio-ventricular node. There was no significant difference in the anterograde and retrograde refractory periods of the accessory pathways between the two groups. Reciprocating tachycardia, initiated by electrical stimulation in 7 patients in Group I and 6 patients in Group II, was conducted anterogradely to the ventricles through the normal pathway and retrogradely to the atria through the the accessory pathway. This study suggest that age-related changes in the electrophysiological properties of the accessory are not an important prognostic factor in the Wolff-Parkinson-White syndrome.

Ventricular tachycardia occurred with chest pain in a 64 year old man with coronary artery disease after an intravenous injection of atropine. The particular feature of this case as compared to the other 8 reported cases is the restoration of sinus rhythm after a passage of accelerated idioventricular rhythm by the administration of oxygen and nitroglycerin. The increased oxygen consumption and myocardial ischaemia due to the tachycardia seem to be the factors responsible for these ventricular arrhythmias. Such cases, though rare, incite caution in the administration of atropine to patients with coronary artery disease.

60 consecutive patients (mean age: 80,7 yrs; s.d.: 6,1 yrs; range 70-94 yrs) referred to a geriatric medicine department with syncope or dizziness were proposectively compared with 40 age and sex matched controls. A battery of non-invasive investigations including tilt-test, glycemia, 12 lead ecg., eeg, 24 hour ambulatory ecg recording,. M--mode echocardiogram and cervical Doppler velocimetry was applied blindly to patients and controls. The proportion of abnormalities was similar in both groups having sick sinus syndrom or complete atrio-ventricular block versus no control (p less than 0.05). By contrast history-case was of great predictive value: 6 of 13 patients reporting abrupt syncope had a 24 ecg recording showing sick sinus syndrom or complete atrio ventricular block, versus 2 of 47 other patients (p less than 0,01); 11 of 14 patients reporting orhostatic dizziness or syncope had a tilt-test consistent with orthostactic hypotension versus 6 of 46 other patients (p less than 0,01).

In order to check the long-term tolerance of a laxative treatment, the authors supervised during six months a group of 14 elderly people (12 women and 2 men) with a mean age of 81.3 years suffering from long-standing constipation without any organic cause. The laxative was given in a daily dosage corresponding to 20 mg of sennosides. Alpha 1-antitrypsin (alpha 1-AT) clearance and exchangeable potassium pool (PPE) were measured, at the beginning (T0), and at the end of the third (T3) and the sixth (T6) months of the study. No abnormal variation of intestinal protein loss (alpha 1-AT: T0, 6.74 +/- 3.16; T3, 2.96 +/- 1.35; T6, 4.15 +/- 1.45 ml/24 h; T0-T3; p less than 0.05, T0-T6, T3-T6: NS) and exchangeable potassium pool (PPE: T0, 19.54 +/- 2.55; T3, 20.29 +/- 3.46, T6, 23.56 +/- 4.92 mEq/kg; T0-T3, T0-T6, T3-T6: NS) was observed. In opposition to current views, all long-term laxative treatments do not necessarily induce significant intestinal protein and potassium losses.

From May 1979 to April 1980, 223 patients were discharged from a "medium stay" unit (mean length of stay: 45 days) for geriatric patients in Bordeaux (France). The outcome at discharge was established from retrospective data, and the long-term outcome (18 months) through a letter sent to general practitioners (rate of response: 88,5% with, in some instances, a prompting phone-call). The mortality rates were 22,5% in hospitalized patients and 38% in survivors after discharge. When those hospitalized for social reasons only are excluded, 62,9% of the remaining patients returned to their former place of residence at discharge. Moreover, 83% were still living at the same place after 18 months (range: 12-24 months). Considering the patients' ages and the seriousness of their conditions, "medium stay", geriatric units seem efficient in helping to maintain the aged at home.