Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.     

Dopaminergic receptor sites in human brain: positron emission tomography

Positron emission tomography (PET) and 11C-labeled pimozide were used to study the dopaminergic (DA) receptor sites in the human striatum by comparing the latter with the cerebellum, which lacks DA receptors. Although 11C-pimozide concentration was not different in these two brain structures up to 53 minutes after IV injection (thus implying large nonspecific binding), a significant retention of radioactivity in striatum relative to cerebellum was found in controls but not in subjects pretreated with the unlabeled competitor haloperidol. This suggests that the striatal retention seen in controls was due to specific binding of 11C-pimozide to DA receptor sites, whereas prior occupation of the receptor sites by the unlabeled competitor was achieved in pretreated subjects.     

Candidaemia and cancer: patients are not all the same

Background  

Most of the studies about invasive Candida infections in cancer patients have focused on haematological patients. The aim of this study was to provide information about risk factors for candidaemia in patients with solid tumours.     

Neuroanatomical Correlates of Visually Evoked Sexual Arousal in Human Males

Brain areas activated in human male sexualbehavior have not been characterized precisely. For thefirst time, positron emission tomography (PET) was usedto identify the brain areas activated in healthy males experiencing visually evoked sexualarousal. Eight male subjects underwent six measurementsof regional brain activity following the administrationof [¹⁵O]H₂O as they viewedthree categories of film clips: sexually explicit clips,emotionally neutral control clips, and humorous controlclips inducing positive but nonsexual emotions.Statistical Parametric Mapping was used to identifybrain regions demonstrating an increased activity associatedwith the sexual response to the visual stimulus.Visually evoked sexual arousal was characterized by athreefold pattern of activation: the bilateralactivation of the inferior temporal cortex, a visualassociation area; the activation of the right insula andright inferior frontal cortex, which are two paralimbicareas relating highly processed sensory information with motivational states; and the activation ofthe left anterior cingulate cortex, another paralimbicarea known to control autonomic and neuroendocrinefunctions. Activation of some of these areas was positively correlated with plasma testosteronelevels. Although this study should be consideredpreliminary, it identified brain regions whoseactivation was correlated with visually evoked sexualarousal in males.     

The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey

Introduction

Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs).

Methods

A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants).

Results

Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20–3.56], rhythm control (OR 1.64, 1.25–2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51–3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis.

Conclusions

NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

     

Labelling and metabolism of methionine-methyl-11C

Carbon 11 which is a 20.4 minutes half life isotope emitting positrons was used for methionine labelling on the methyl group by action of ¹¹C-methyl-iodide on DL or L homocysteine. With the method described, 20 to 30 mCi of ¹¹C-methyl-methionine (Specific activity 50 mCi/M) may be obtained within 25 minutes. The 20 Mev proton beam used for ¹¹C production was 10 A. The metabolism of ¹¹C methionine studied on mice shows a high uptake in pancreas and to a smaller extent in brain. On humans sequential images were obtained at the head level which allowed measurement of the uptake of the radio-labelled compound in the brain so as to study the radioactivity curve in different parts of the organ.Chercheur au CNRS     

Nicotine-11C: Synthesis and distribution kinetics in animals

In order to study in vivo the distribution kinetics of (-)-nicotine in animals, this molecule was labeled with carbon-11. Two synthesis methods are described. Immediately after intravenous administration of (-)-nicotine-methyl-¹¹C in rabbits the gamma-camera shows a strong radioactivity build-up in the brain and kidneys. The biological interest of this carbon-11 labeled molecule is discussed.     

Comparison of dengue-1 virus envelope glycoprotein gene sequences from French Polynesia

Dengue (DEN) is the leading arboviral infection of humans, with 100 million cases annually in the tropical areas of the world. The recent severe DEN-1 epidemic in French Polynesia in 2001, with an incidence rate of 16% and more than 45% of the cases with dengue hemorrhagic fever/dengue shock syndrome among 1,400 hospitalized children and eight fatalities, led us to study this new circulating strain. The entire envelope (E) gene of two French Polynesian DEN-1 virus isolates from the two epidemics of 1988-1989 (FP89) and 2001 (FP01) were sequenced and compared with 29 published DEN-1 virus E gene sequences. Phylogenetic relationships showed that the FP89 strain belonged to genotype V and the FP01 strain to genotype IV based on studies on the same region of DEN-1 virus genome (1,485 nucleotides). The recent dengue epidemic in French Polynesia in 2001 was probably due to the introduction of a new DEN-1 virus from Southeast Asia, since the minimum nucleotide divergence was 3.3% with A88, the Indonesian strain isolated in 1988 in Jakarta.     

Interferon plus ribavirin in patients with hepatitis C virus positive mixed cryoglobulinemia resistant to interferon

OBJECTIVE: Only a small fraction of patients with hepatitis C virus (HCV) positive mixed cryoglobulinemia achieve longterm recovery after interferon (IFN) therapy; we evaluated the effectiveness and safety of combination therapy (interferon plus ribavirin) in nonresponders or those who relapsed after one or more courses of IFN. METHODS: Twenty-seven patients with HCV positive mixed cryoglobulinemia were studied. All were treated with IFN-a2b (3 MU 3 times weekly) for one year, plus daily oral ribavirin 1000 or 1200 mg. RESULTS: Five patients (18.5%) obtained complete recovery from viral infection and from all signs and symptoms of disease. During treatment, most patients (85%) improved clinically. All 5 responders were "relapsers" to the first treatment(s). CONCLUSION: Combination therapy of IFN plus ribavirin could be useful for patients with mixed cryoglobulinemia resistant to IFN as monotherapy.     

Failure of Intracardiac Pacing After Fatal Propafenone Overdose: A Case Report

Background

Propafenone is a sodium-channel blocker, class IC antiarrhythmic drug, frequently used to manage supraventricular dysrhythmias, especially atrial fibrillation. We report a self mono-intoxication with propafenone.