Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol. 2003 24(3):481-487]. In this study, we tested the hypothesis that such a relationship does exist not only in AD patients but also across the continuum of subjects with mild cognitive impairment (MCI) and AD. METHODS: Resting, eyes-closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. Cortical EEG sources were correlated with MR-based measurements of lobar brain volume (white and gray matter). RESULTS: A negative correlation was observed between the frontal white matter and the amplitude of frontal delta sources (2-4 Hz) across MCI and AD subjects. CONCLUSIONS: These results confirmed for the first time the hypothesis that the sources of resting delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD subjects. SIGNIFICANCE: The present findings support, at least at group level, the 'transition hypothesis' of brain structural and functional continuity between MCI and AD.     

A mating deficient and temperature-sensitive lethal mutant of Schizosaccharomyces pombe defines a new fertility locus

Summary A recessive mutant allele, mef1-84, of a novel locus mapping on the left arm of chromosome I, between ade3 and ura1, 5 cM apart from lys5, confers temperature-sensitive growth and mating deficiency at the nonrestrictive temperatures for growth. Two other mutations suppress the phenotype conferred by mef1-84: sts1-1 suppresses the temperature-sensitive growth only, and smd1-35 suppresses both temperature-sensitive growth and mating deficiency.     

Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen.

PURPOSE: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients. EXPERIMENTAL DESIGN: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses. RESULTS: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4+ and CD8+ T cells, were human lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission. CONCLUSIONS: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4+ and CD8+ T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.     

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

Introduction: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Methods: Thirty‐two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B‐type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Results: Patients were followed for 14 months (7.5–21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than ?13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8–0.96), P = 0.007. Conclusions: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.     

Antibacterial activity of aminals and hemiaminals of pyrazole and imidazole

Antibacterial activity of 1,1′-methylenedipyrazole (AM1), 1-hydroxymethylpyrazole (SAM1), 1,1′-methylenediimidazole (AM2), and 1-hydroxymethylimidazole (SAM2) has been tested against reference and clinical strains by both difusimetric and broth dilution methods. Overall, the minimal inhibitory concentrations of tested compounds ranged from 180 to 270?μg/ml, while the minimal bactericidal concentrations were between 360 and 720?μg/ml. Comparative assessment with phenol and formaldehyde shows that AM1, AM2, SAM1, and SAM2 have moderate to good antibacterial activity.     

Hb Calais [β76(E20)Ala→Pro]: A Family Study of a Variant With Decreased Oxygen Affinity

Secondary to the detection of a chronic anemia with a slightly increased Hb F level in a 7‐year-old boy carrying a hemoglobin (Hb) variant, we investigated the members of his family and found that they were related to the original case of Hb Calais. In the present study, we report the clinical and biological impacts of this Hb variant in various members of three generations of this family.     

Nuclear medicine dynamic investigations of diffuse chronic liver diseases and portal hypertension

Radio-isotopic techniques may be useful in diagnosis and staging of chronic diffuse liver diseases. Liver angioscintigraphy (LAS) and per-rectal portal scintigraphy (PRPS) are at well discriminating portal hypertension (PHT), very early cirrhosis hemodynamic failure and compensatory arterialisation of liver perfusion. Supplied information is related to PHT, liver morphology and mesenchimal activity in liver, spleen and bone marrow. Correlation of LAS and PRPS may diagnose installing of PHT earlier than any actual morphologic imagistic method. Our experience (after more than 300 PRPS and 500 LAS) suggests that PHT and portal-cave shunts (PCS) may be classified in five functional stages. These five patterns (types) are characteristic for portal dynamics, supporting disease staging and follow-up of evolution to cirrhosis. All five dynamics may be assessed by PRPS and LAS. Scintigraphic techniques also explore portal thromboses, perfusion differences between the lobes of cirrhotic liver, betablockers effect in PHT, earliest stages of PHT, malignant tumours occurring on cirrhosis, the different characteristics of alcoholic liver comparing to viral etiology.     

Staging of portal hypertension and portosystemic shunts using dynamic nuclear medicine investigations

AIM： To explore portal hypertension and portosystemic shunts and to stage chronic liver disease （CLD） based on the pathophysiology of portal hemodynamics. METHODS： Per-rectal portal scintigraphy （PRPS） was performed on 312 patients with CLD and liver angioscintigraphy （LAS） on 231 of them. The control group included 25 healthy subjects. We developed a new model of PRPS interpretation by introducing two new parameters, the liver transit time （LTT） and the circu-lation time between right heart and liver （RHLT）. LTT for each lobe was used to evaluate the early portal hypertension. RHLT is useful in cirrhosis to detect liver areas missing portal inflow. We calculated the classical per-rectal portal shunt index （PRSI） at PRPS and the hepatic perfusion index （HPI） at LAS. RESULTS： The normal LTT value was 24 ± 1 s. Abnormal LTT had PPV = 100% for CLD. Twenty-seven noncirrhotic patients had LTT increased up to 35 s （median 27 s）. RHLT （42 ± 1 s） was not related to liver disease. Cirrhosis could be excluded in all patients with PRSI 〈 5% （P 〈 0.01）. PRSI 〉 30% had PPV = 100% for cirrhosis. Based on PRPS and LAS we propose the classification of CLD in 5 hemodynamic stages. Stage 0 is normal （LTT = 24 s, PRSI 〈 5%）. In stage 1, LTT is increased, while PRSI remains normal. In stage 2, LTT is decreased between 16 s and 23 s, whereas PRSI is increased between 5% and 10%. In stage 3, PRSI is increased to 10%-30%, and LTT becomes undetectable by PRPS due to the portosystemic shunts. Stage 4 includes the patients with PRSI 〉 30%. RHLT and HPI were used to subtype stage 4. In our study stage 0 had NPV = 100% for CLD, stage 1 had PPV = 100% for non-cirrhotic CLD, stages 2 and 3 represented the transition from chronic hepatitis to cirrhosis, stage 4 had PPV = 100% for cirrhosis. CONCLUSION： LTT allows the detection of early portal hypertension and of opening of transhepatic shunts. PRSI is useful in CLD with extrahepatic portosystemic shunts. Our hemodynamic model stag