Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder.

OBJECTIVE: The objective of the study was to investigate the relationship between structural connectivity (SC) and functional connectivity (FC) in the cingulum in bipolar disorder (BD) and its various phases. METHOD: We combined resting-state functional magnetic resonance imaging and probabilistic tractographic diffusion tensor imaging to investigate FC and SC of the cingulum and its portions, the SC-FC relationship, and their correlations with clinical and neurocognitive measures on sustained attention in manic (n = 21), depressed (n = 20), and euthymic (n = 20) bipolar patients and healthy controls (HC) (n = 42). RESULTS: First, we found decreased FC between the anterior and posterior parts of the cingulum in manic patients when compared to depressed patients and HC. Second, we observed decreased SC of the cingulum bundle, particularly in its anterior part, in manic patients when compared to HC. Finally, alterations in the cingulum FC (but not SC) correlated with clinical severity scores while changes in the cingulum SC (but not FC) were related with neurocognitive deficits in sustained attention in BD. CONCLUSION: We demonstrate for the first time a reduction in FC and concomitantly in SC of the cingulum in mania, which correlated with psychopathological and neurocognitive parameters, respectively, in BD. This supports the central role of cingulum connectivity specifically in mania.

Human monocytic cell lines derived from cord leukocytes by co-cultivation with irradiated CM-S cells.

The CM-S cell line was established from the bone marrow of a child with congenital hypoplastic anemia and resembles its monocyte-macrophage lineage. Lethally x-irradiated CM-S cells from various passages and clones, representing different stages in the progression of the transformed growth phenotype, were tested for their ability to affect the survival and proliferation of normal human cord or adult blood leukocytes in co-culture. One clone, CM-SM, which is tumorigenic in athymic mice, consistently immortalized umbilical cord mononuclear cells but did not immortalize adult peripheral blood leukocytes. Six autonomous monocyte-like diploid cell lines were obtained and all were found to be of cord origin. Three lines were tumorigenic in athymic mice. Attempts to immortalize human leukocytes with cell-free supernatants from CM-S cells were unsuccessful.

Runaway electron imaging spectrometry (REIS) system.

A portable Runaway Electron Imaging and Spectrometry System (REIS) was developed in ENEA-Frascati to measure synchrotron radiation spectra from in-flight runaway electrons in tokamaks. The REIS is a wide-angle optical system collecting simultaneously visible and infrared emission spectra using an incoherent bundle of fibers, in a spectral range that spans from 500 nm to 2500 nm, and visible images using a CCD color microcamera at a rate of 25 frames/s. The REIS system is supervised and managed using a dedicated LabVIEW program to acquire data simultaneously from three spectrometers every 20 ms (configurable down to 10 ms). An overview of the REIS architecture and acquisition system and resulting experimental data obtained in FTU are presented and discussed in this paper.

High seroprevalence of antibodies to human herpesvirus-8 in Egyptian children: evidence of nonsexual transmission.

BACKGROUND: In western countries, human herpesvirus-8 (HHV-8) appears to be transmitted mainly by sexual contact. To evaluate the role of other transmission routes, especially in developing countries, we estimated the seroprevalence of HHV-8 in Egyptian children, who, if seropositive, would have acquired the virus through a nonsexual route. METHODS: Sera from 196 children (<1-12 years of age), 20 adolescents (13-20 years of age), and 30 young adults (21-25 years of age) attending a vaccination program in Alexandria, Egypt, were studied. Immunofluorescence assays were used to detect antibodies against HHV-8 lytic-phase antigens (anti-lytic) and latent-phase antigens (anti-latent). Antibodies against Epstein-Barr virus viral cap antigen, cytomegalovirus, and HHV-6 were detected by enzyme-linked immunosorbent assays. Seroprevalence of these herpesviruses was calculated after stratifying the subjects by age. RESULTS: Anti-lytic and anti-latent HHV-8 antibodies were detected in 44.7% and 8.5% of the study participants, respectively. The prevalence of anti-lytic antibodies tended to increase with age, exceeding 50% in children older than 6 years; once children reached the age of 10 years, the prevalence tended to stabilize. The seroprevalence of other herpesviruses tended to be higher than that of HHV-8, ranging from approximately 83% to more than 97% in the 9- to 12-year age group. One- to 3-year-old children had higher titers of antilytic HHV-8 antibodies than children in the other age groups. Anti-latent antibodies were more frequently detected in individuals with high anti-lytic antibody titers. CONCLUSIONS: HHV-8 antibodies are highly prevalent in Egyptian children, suggesting that, in developing countries, HHV-8 infection may be acquired early in life through routes other than sexual transmission. The lower seroprevalence of HHV-8 relative to that of the other herpesviruses suggests that HHV-8 is less transmissible than other common herpesviruses.

Implementation of the new multichannel X-mode edge density profile reflectometer for the ICRF antenna on ASDEX Upgrade.

A new multichannel frequency modulated continuous-wave reflectometry diagnostic has been successfully installed and commissioned on ASDEX Upgrade to measure the plasma edge electron density profile evolution in front of the Ion Cyclotron Range of Frequencies (ICRF) antenna. The design of the new three-strap ICRF antenna integrates ten pairs (sending and receiving) of microwave reflectometry antennas. The multichannel reflectometer can use three of these to measure the edge electron density profiles up to 2 × 1019 m-3, at different poloidal locations, allowing the direct study of the local plasma layers in front of the ICRF antenna. ICRF power coupling, operational effects, and poloidal variations of the plasma density profile can be consistently studied for the first time. In this work the diagnostic hardware architecture is described and the obtained density profile measurements were used to track outer radial plasma position and plasma shape.

High rate of HIV isolation from plasma of asymptomatic patients through polyethylene glycol (PEG) treatment.

The usefulness of traditional methods of HIV plasma titration has been limited by poor detection capacity in the asymptomatic phase of HIV disease. We analyzed plasma samples from asymptomatic seropositive or early symptomatic patients, comparing the classic plasma culture method with the following techniques: phorbol 12-myristate 13-acetate treatment of target cells, centrifugal inoculation of the virus, heat treatment of cultures, addition of monocyte/macrophages to cultures, and polyethylene glycol (PEG) treatment of the plasma. Only PEG treatment significantly increased the percentage of HIV isolation. The increase of HIV isolation after PEG treatment is more evident in patients with higher CD4+ cell counts and those without detectable levels of p24 antigen. In the p24-negative samples, HIV was isolated in 17 of 24 (71%) with PEG treatment versus nine of 24 (37%) with the classic method (p < 0.01). A number of discordant samples were found using the classic and PEG methods. Combining the positive results obtained with either technique, we obtained an overall HIV detection rate of 76%. The increased sensitivity of the combination of PEG and classic methods may allow a wider use of plasma viremia as part of the virological evaluation of anti-HIV drug efficacy in asymptomatic patients.

Assessment of restrictive cardiomyopathy of amyloid or idiopathic etiology by magnetic resonance imaging.

This study was designed to assess the role of magnetic resonance imaging in the differential diagnosis of amyloid and idiopathic etiology of cardiomyopathy. This technique demonstrated the capability to differentiate the 2 forms, providing high-resolution evaluation of the myocardial wall and detecting the infiltrative pathology by tissue characterization.

Effect of harmonic imaging without contrast on image quality of transesophageal echocardiography.

Harmonic imaging improves endocardial border delineation during transesophageal echocardiography when compared with conventional imaging (26% improvement vs 2% worsening; p <0.001). This allows better assessment of left ventricular function during cardiac surgery, and suggests a role of harmonic imaging for transesophageal echocardiography.

Usefulness of power Doppler contrast echocardiography to identify reperfusion after acute myocardial infarction.

Microvascular integrity, as seen by myocardial contrast echocardiography (MCE), assesses whether myocardium has been successfully reperfused after an acute myocardial infarction. Until now this has been demonstrated only with intracoronary injection of an ultrasound contrast agent. Power Doppler imaging is a recently developed myocardial contrast echocardiographic method that counts the contrast microbubbles destroyed by ultrasounds and displays this number in color. This study sought to evaluate whether power Doppler MCE is able to visualize myocardial reperfusion during intravenous contrast injection. Thirty patients were evaluated 2 days after their first myocardial infarction during intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA). Coronary artery angiography and single-photon emission computed tomography (SPECT) were used as reference techniques. A 16-segment left ventricular model was used to relate perfusion to coronary artery territories. Sensitivity and specificity of power Doppler MCE for segments supplied by infarct-related arteries were 82% and 95%, respectively. Accuracy of power Doppler MCE and SPECT were similar (90% vs 92% on segmental basis and 98% vs 98% on coronary artery territory basis). Two-dimensional echocardiography was repeated after 6 weeks. Segments recovering wall motion after 6 weeks were defined as stunning myocardium. Dysfunctional but perfused myocardium at day 2 after the infarction showed a better late recovery of wall motion compared with dysfunctional but nonperfused myocardium (p <0.001). In conclusion, harmonic power Doppler imaging is a sensitive and specific method for the identification of myocardial reperfusion early after myocardial infarction. It yields prognostic information for late recovery of ventricular function differentiating stunning (dysfunctional but perfused) from necrotic myocardium (dysfunctional and nonperfused).

Usefulness of transesophageal echocardiographic monitoring to improve the outcome of stent-graft treatment of thoracic aortic aneurysms.

The stent-graft procedure is becoming an alternative to surgery for treatment of many diseases of the descending thoracic aorta. This study evaluated the role of transesophageal echocardiography (TEE), used in combination with fluoroscopy and angiography, in monitoring the outcome of stent-graft placement. Twenty-two consecutive patients were submitted to stent-graft positioning in the descending aorta for various pathologies (7 patients had type B aortic dissections, 6 had thoracic aneurysms, 2 had thoraco-abdominal aneurysms, and 7 had post-traumatic aortic aneurysms). Before stent-graft deployment, TEE changed the proximal site of stent positioning initially identified by angiography in 33% of patients (5 of 15) with aortic aneurysms because of calcifications or atheromas that could interfere with stent adhesion to the aortic wall and that were not seen on angiography. In 28% of patients (2 of 7) with aortic dissection, TEE showed the guidewire in the false lumen, allowing an immediate repositioning. After stent-graft deployment, color Doppler TEE showed a perigraft leak in 7 patients, whereas angiography detected a perigraft leak in only 2 patients (p = 0.02). In 4 of these patients, further balloon expansions resulted in resolution of the leak. In the remaining 3 patients, additional stent-graft positioning was necessary. Considering the total patient cohort, TEE yielded relevant information, resulting in procedure changes in 59% (13 of 22). In conclusion, TEE provided additional information with respect to angiography in all phases of stent-graft treatment, improving immediate outcome and reducing complications.

Usefulness of the ejection fraction response to dobutamine infusion in predicting functional recovery after coronary artery bypass grafting in patients with left ventricular dysfunction.

Quantification of dysfunctional but viable myocardium has high prognostic value for improvement of left ventricular (LV) function after coronary artery bypass grafting (CABG). Dobutamine stress echocardiography (DSE) can assess viable myocardium by segmental wall motion changes during stress. However, analysis of wall motion is subjective with only moderate interinstitutional agreement (70%) and frequently overestimates functional improvement after CABG. In contrast, calculation of ejection fraction (EF) is less subjective and allows a more precise quantification of global contractile reserve. The aim of the study was to compare the prognostic value of EF response and segmental wall motion changes during DSE for the prediction of LV functional recovery after CABG. Forty patients underwent DSE before CABG. EF responses were assessed at rest, low-dose dobutamine, and at peak stress using the biplane disk method. Wall motion was scored using a 16-segment 5-point model. Resting radionuclide ventriculography (RNV-LVEF), performed before and 8 +/- 2 months after CABG, was used as an independent reference. Five patients were excluded because of perioperative infarction or poor echo images. In 11 of 35 patients, RNV-LVEF recovered >5%. Improvement in EF during dobutamine infusion predicted RNV-LVEF recovery after CABG significantly better than segmental wall motion changes (72% vs 53%, p = 0.03). A biphasic EF response (i.e., improvement in > or =10% at low dose and subsequent worsening at peak stress) had the highest predictive value (80%) for late functional recovery. In conclusion, EF response to dobutamine infusion was superior to segmental wall motion changes in predicting RNV-LVEF recovery after CABG.

Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes.

Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M. We further investigated the mechanism(s) of action of ADR and its potential synergistic activity with zidovudine (AZT) or alpha-interferon (IFN alpha). ADR consistently inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005 micrograms/ml ADR, while greater 90% viral inhibition was obtained with 0.05 micrograms/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5 micrograms/ml. No anti-HIV activity was shown by ADR in lymphocytes at concentrations up to 0.05 micrograms/ml, that is also the toxic dose 50% (TCID50 for these cells). ADR neither inactivates HIV virions nor affects HIV binding with CD4 receptors. No inhibition of HIV reverse transcriptase by ADR was found at concentrations at least 2,000-fold greater than the 50% HIV inhibitory concentration in M/M. Molecular analysis by polymerase chain reaction (PCR) suggests that ADR substantially affects virus DNA production at concentrations that inhibit viral replication. Finally, late stages of HIV replication were not affected by ADR. At least additive effects of the association ADR + AZT and ADR + IFN alpha were obtained against de novo HIV infection of M/M.(ABSTRACT TRUNCATED AT 250 WORDS)

Ability of anti-HIV agents to inhibit HIV replication in monocyte/macrophages or U937 monocytoid cells under conditions of enhancement by GM-CSF or anti-HIV antibody.

Monocyte/macrophages (M/M) are an important target cell for human immunodeficiency virus (HIV) infection in the body. The study of HIV infection in these cells, however, is rather complicated because they represent a variable population, and because HIV entry and replication in M/M may be markedly influenced by a number of factors. These must be considered in therapeutic approaches to HIV infection. In the present set of experiments, we studied the interaction between certain agents which increase the infection of monocyte/macrophages (M/M) by HIV and two groups of anti-HIV agents: dideoxynucleosides and specific inhibitors of gp120-CD4 binding. We found that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which markedly enhances HIV replication in M/M, does not affect the activity of recombinant soluble CD4 (sCD4) or OKT4A, two agents which block gp120-CD4 binding. However, it had varying effects on different dideoxynucleosides: GM-CSF increased the net anti-HIV activity of 3'-azido2',3'-dideoxythymidine (AZT), while at the same time it reduced the activity of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). These effects probably represent an interplay between varying effects of GM-CSF on drug entry and phosphorylation. In additional experiments, we showed that very low concentrations of anti-HIV antibodies could enhance HIV infection of the U937 monocytoid cell line. Interestingly, while this effect has been hypothesized to occur through a CD4-independent mechanism, we found that the anti-HIV activities of both sCD4 and OKT4A were unchanged under conditions of enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)

Unfavourable effects of colchicine in combination with interferon-alpha in the treatment of chronic hepatitis C.

BACKGROUND: The prognosis of chronic hepatitis depends on the progression of hepatic fibrosis. AIM: To investigate whether the antifibrotic drug colchicine, in combination with interferon-alpha has a role in the treatment of chronic hepatitis C. METHODS: Sixty-five HCV-RNA positive patients with chronic hepatitis were randomized to receive interferon-alpha, 6 MU t.i.w. for 6 months followed by 3 MU t.i.w. for further 6 months, with or without the adjunct of colchicine, 1 mg o.d., 6 days a week, for 3 years. We report an interim analysis after the first 18 months. RESULTS: Thirty-four patients received interferon-alpha and 31 received interferon-alpha and colchicine. The two groups were comparable for baseline data, including HCV-RNA levels, genotypes and histological grading/staging. Drop-outs and side-effects were similar. The proportion of patients who achieved alanine transaminase normalization or undetectable HCV-RNA at month 6 was higher in the interferon-alpha (68% and 47%, respectively) than in the interferon-alpha plus colchicine group (32% and 23%, P=0.004 and P=0. 04, respectively). End-of-treatment biochemical and virological response occurred in 41% and 29% of the interferon-alpha and 19% and 10% of the combination group, respectively (P=0.05 and P=0.05). Sustained biochemical response occurred in 26% of the interferon-alpha and 6% of the interferon-alpha plus colchicine group (P=0.03), corresponding percentages of sustained HCV-RNA loss being 21% and 3% (P=0.04). CONCLUSIONS: The combination of colchicine and interferon-alpha worsens the effectiveness of interferon-alpha alone in HCV chronic hepatitis. These alarming findings prompted us to interrupt the trial at this stage.

Primary endoleakage in endovascular treatment of the thoracic aorta: importance of intraoperative transesophageal echocardiography.

OBJECTIVES: Endovascular treatment of the thoracic aorta has developed as an efficacious alternative to open surgical repair. However, despite the high primary success rate, perigraft leakage constitutes the major concern in long-term follow-up. Endoleaks are widely reported both in abdominal and thoracic endovascular series and are usually identified by intraoperative angiography. Transesophageal echocardiography is a sensitive imaging technique in the evaluation of aortic diseases, widely used to monitor cardiac surgery. The aim of this study was to evaluate the efficacy of transesophageal echocardiography in leakage detection during endovascular stent procedures of the thoracic aorta. METHODS: Intraoperative transesophageal echocardiography was used in conjunction with angiography in 25 patients subjected to endovascular stent treatment of the descending thoracic aorta. Spiral computed tomographic scanning was performed before discharge and 3, 6, and 12 months after treatment. RESULTS: Information from transesophageal echocardiography was relevant in the selection of the landing zone in 62% of cases. In 8 patients, transesophageal echocardiography with color Doppler sonography showed a perigraft leak, 6 of which were not visible on angiography, suggesting the need for further balloon expansion or graft extension. Postoperative computed tomographic scanning in the 25 patients showed 1 endoleak, which sealed spontaneously. At 3 months, computed tomographic examination confirmed the absence of perigraft leakage in all patients. CONCLUSIONS: During implantation of a stent-graft in the descending thoracic aorta, transesophageal echocardiography provides information in addition to that provided by angiography, improving immediate and late procedural results.

Different pattern of activity of inhibitors of the human immunodeficiency virus in lymphocytes and monocyte/macrophages.

Monocyte/macrophages (M/M) are important targets for HIV in the body, and represent the majority of cells infected by the virus in some body compartments such as the central nervous system (CNS). M/M can be different from T-lymphocytes in terms of surface antigens, cell replication and drug metabolism. Thus, we evaluated, in M/M and in T-lymphocytes, the pattern of viral inhibition induced by various anti-HIV drugs, and assessed some of the mechanisms of action related to such antiviral activity. Inhibitors of HIV binding on CD4 receptors have similar activity in M/M and T-lymphocytes, while AZT and other dideoxynucleosides (ddN) are in general more active against HIV in M/M than in T-lymphocytes. This phenomenon can be related to the increased ratio in M/M of ddN-triphosphate/deoxynucleoside-triphosphate, and can at least in part explain the ability of zidovudine and didanosine in improving neurological dysfunctions in AIDS patients. Moreover, the antiviral activity of AZT (but not of other ddN- or HIV-binding inhibitors) is potently enhanced by cytokines like granulocyte-macrophage colony stimulating factor (GM-CSF) in M/M, while anti-HIV activity of TIBO compounds in M/M is not down-modulated by GM-CSF and other cytokines. Finally, non-toxic concentrations of adriamycin, an anticancer drug reported to be active against DNA viruses, can inhibit HIV replication in M/M (but not in T-lymphocytes). Taken together, these results suggest that M/M are selective targets for HIV with peculiarities different from those of T-lymphocytes. Thus, promising anti-HIV compounds should be evaluated both in T-cells and in M/M before reaching clinical trials. This may help in selecting drugs with good chances of being effective in patients with HIV-related disease.

A tetrazolium-based colorimetric assay for quantification of HIV-1-induced cytopathogenicity in monocyte-macrophages exposed to macrophage-colony-stimulating factor.

A sensitive assay was developed for in vitro evaluation of anti-HIV agents in monocyte-macrophage cells (M/M) (a crucial target of HIV in the body). Monocyte-macrophage cells are usually poorly sensitive to the cytopathic effect induced by HIV. However, when fresh adherent monocyte-macrophage cells are cultured at relatively high density in the presence of macrophage-colony stimulating factor (M-CSF), they undergo cytolysis and die in 2-3 weeks. HIV-mediated cell-killing can thus be assessed with a method based on the reduction of the yellow colored 3-(4-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by metabolically active cells to a blue formazan, which can be measured spectrophotometrically. HIV-mediated cytopathic effect of M-CSF-exposed monocyte-macrophage cells was consistently achieved in all experiments performed under the conditions described herein. Anti-HIV activity of zidovudine (AZT) was also comparatively evaluated in M-CSF- and normal monocyte-macrophage cells both using the MTT assay and by measuring HIV-p24 antigen production in supernatants of monocyte-macrophage cells cultures, and similar results obtained with both methods. These results support the use of this colorimetric assay for broad screening of anti-HIV agents in monocyte-macrophage cells.

Effect of Cyclosporin A on prostacyclin synthesis by vascular tissue.

NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seem in the haemolytic uraemic syndrome (HUS). Bone marrow recipients treated with CyA may also develop a similar renal lesion associated with a haemolytic uraemic-like syndrome. In the HUS, impaired production of prostacyclin by vascular tissue may be found and has been associated with a lack of a plasma factor which stimulates prostacyclin synthesis. We therefore examined, in six normal rabbits, treated with CyA 25 mg/kg for five days, the ability of plasma from treated and untreated rabbits to stimulate prostacyclin synthesis from normal rabbit aortic rings. Plasma from untreated rabbits produced 21.5 +/- 6.9 ng 6-keto PGF1 alpha/ml/mg wet weight aorta (mean +/- SEM). However, the ability of plasma from CyA-treated rabbits to stimulate prostacyclin production was profoundly reduced. This was apparent within 24 hours of starting and persisted for seven days after therapy was stopped: mean of values from all rabbits bled from start of therapy until seven days after therapy stopped was 3.7 +/- 0.5 ng/ml/mg. We suggest that the renal complications of CyA therapy are related to a failure of normal vascular prostacyclin synthesis due to lack of a prostacyclin-stimulating plasma factor.

Neurinoma of the oculomotor nerve.

A rare case of neurinoma of cranial nerve III is described. Preoperative diagnosis of such tumors is difficult because they may be mistaken for brainstem tumors.

Extradural haematoma of posterior cranial fossa.

Two cases of extradural haematoma of posterior fossa with an acute course are reported. After trauma, the two patients did not show any symptom for a time of 16 and 18 hours respectively. Both of them showed a status of coma at the moment of hospitalization. The haematoma was diagnosed by CT scan. Both of them were immediately operated in order to evacuate the haematoma. Afterwards, one of the patients presented cerebellar symptoms while the other did not show any neurologic deficiency. The authors have analysed cases of this rare form of post-traumatic pathology referred in the literature since 1941, examining them from a clinical, therapeutic and prognostic point of view. The best diagnostic and therapeutic procedures to follow on this subject are then stressed.