Oral stomatitis induced by endogenous progesterone: Case report

Oral stomatitis induced by endogenous progesterone is a rare clinical condition which may be associated with cutaneous involvement. That is probably due to the peak of progesterone production during the luteal phase of the menstrual cycle. In the present case report, a 21-year-old patient displayed recurrent ulcerative lesions located on the buccal mucosa or the upper lip, on a monthly basis since the age of 15. Such lesions would always manifest themselves on the second day until the end of the menstrual cycle.     

Endophotocoagulation through perfluorodecalin in rabbit eyes

Retinal laser endophotocoagulation through perfluorodecalin was studied in six eyes of three Dutch-belted rabbits after vitrectomy. Both the energy density threshold (EDT/50) and the energy threshold necessary to obtain a therapeutic lesion were evaluated. Both argon and semiconductor diode laser endophotocoagulators were used. The amount of laser power energy and the histology of chorioretinal lesions were similar when photocoagulating through perfluorodecalin, compared to photocoagulation through balanced salt citrate-buffered solution. This experimental study indicates that no extra care is necessary when retinal endophotocoagulation is performed through perfluorodecalin, as long as circular spots are obtained and energy is delivered symmetrically to the target site.     

Antifungal Agents,Part 11: Biphenyl Analogues of Naftifine: Synthesis and Antifungal Activities

A series of naftifine analogues having the biphenyl instead of the naphthyl moiety have been synthesized in a search devoted to study bioanalogues of clinically efficacious antifungal agents. The new derivatives were tested against Candida albicans by the direct contact method. They were also assayed against Gram-positive and Gram-negative bacteria and against some isolates of plant pathogenic fungi. Derivatives 8a, 8c , and 9a were found to be active against Candida albicans, derivative 5a was active against E. coli, a very resistant species to antimycotic agents, and derivatives 8a and 8b inhibited the plant pathogenic Rhizoctonia solani.     

Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson's disease: A pilot study

Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson's disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson's disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.     

Adjuvants in vaccines and for immunisation: current trends

Vaccines represent one of the most successful strategies in medical science. From the mechanistic perspective, vaccination works by manipulating the immune response through selecting, activating and expanding the memory of B and T cells. To determine the magnitude and quality of immune response, suitable vaccine adjuvants are required; therefore, much effort is going into finding new, effective and non-toxic adjuvant formulations focussed on the activation of key immune targets for inducing a long-term, potent and safe immune response. Significant research is being done in this area, to develop new classes of vaccines for use not only against infectious diseases, but also in the treatment of autoimmune disorders, allergies, chronic inflammatory diseases and cancer. Here the authors review and classify some of the main vaccine adjuvants on the basis of their immunomodulating properties on the immune system.     

Redirected activity of human antitumor chimeric immune receptors is governed by antigen and receptor expression levels and affinity of interaction

Novel Ab-based immunotherapeutic strategies have exploited T-cell receptor-like chimeric immune receptors (CIR) expressed on the surface of transduced human peripheral blood mononuclear cell (PBMC) to redirect potent non-major histocompatibility complex-dependent cytotoxicity to tumor cells expressing a tumor-associated antigens. We transduced human PBMC with 2 fully human CIRs that trigger through the zeta-chain of CD3 and contain either one of two human scFv specific for the same epitope on the extracellular domain of HER2 but with distinctly different affinities (KD 1616 and 1 nM) for this antigen. Potent direct CIR-mediated killing and in vitro tumor growth inhibition mediated by transduced PBMC were observed against targets expressing different levels of HER2. High-affinity CIR showed stronger ability to bind Ag and retain binding than low-affinity CIR. When lytic potential of the 2 CIRs was evaluated, their efficiency was comparable under conditions of high CIR and Ag expression, whereas low-affinity CIR was more efficient than high-affinity CIR in conditions of limiting Ag and CIR expression levels. When tumor growth inhibition was evaluated, Ag and CIR levels, rather than CIR affinity appeared relevant. Ag-driven CIR activation resulted in the production of soluble factors mediating efficient bystander effect. By carefully defining CIR surface expression and increasing affinity for a specific target antigen, it may be possible to selectively exclude CIR-mediated activity against targets expressing low levels of antigen, as normal cells. On the contrary, low antigen-expressing tumor variants could be eliminated by decreasing CIR affinity. Tuning CIR expression and affinity might help in discriminating different biologic contexts.     

Hypersensitivity reactions to biological agents with special emphasis on tumor necrosis factor-alpha antagonists

PURPOSE OF REVIEW: Several biological agents have been introduced into the drug market and more are emerging. Adverse reactions to these agents have recently been classified into five different subtypes. Some of these reactions are frequent but without consequences for the patients. Others are less frequent but potentially life-threatening, and they include allergic reactions. RECENT FINDINGS: Hypersensitivity reactions are well described adverse drug reactions, corresponding to the ss-type of the newly proposed classification of adverse reactions induced by biological agents. We focus our search on tumor necrosis factor-alpha antagonists, as they represent a dramatic improvement in the therapy of both rheumatic and inflammatory bowel diseases and because adverse reactions have been closely scrutinized. We also add cases from our own experience. We found very few properly documented allergic reactions. SUMMARY: Hypersensitivity reactions to tumor necrosis factor-alpha antagonists are not rare. Whether these manifestations have to be considered type beta or type gamma reactions is still a matter of debate. There is a need for allergological tests in vivo and in vitro.     

Advanced head and neck cancer in older adults: Results of a short course accelerated radiotherapy trial

ObjectivesTo assess the feasibility and safety of a repeated SHort course Accelerated RadiatiON therapy (SHARON) regimen in the palliative setting of Head and Neck (H&N) cancer in older adults.Material and MethodsPatients with histological confirmed H&N cancers, age ≥ 80 years, expected survival >3 months, and Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 were enrolled. Patients were treated in cohorts of six patients: a total dose of 20 Gy was delivered in 2 consecutive days with a twice-daily fractionation (5 Gy per fraction) and at least 8-h interval. If no Grade 3 toxicity was registered, a second enrollment started with another cohort of six patients to whom were administered two cycles (total dose of 40 Gy). The primary endpoint was to evaluate the feasibility of the two cycles of treatment. Secondary endpoints were evaluation of symptoms control rate, symptoms-free survival (SFS), and Quality of Life (QoL) scores.ResultsSeventeen consecutive patients (median age: 85 years) were treated. Nine patients were treated with one cycle and 8 patients with two cycles. No G3 toxicity was reported in either cohort. With a median follow-up time of 4 months, 3-month SFS in the first and second cohorts was 83.3%, and 87.5%, respectively. The overall palliative response rate was 88%. Among 13 patients reporting pain, 8 (61.5%) showed an improvement or resolution of their pain.ConclusionRepeated short course accelerated radiotherapy in a palliative setting of H&N cancers is safe and well-tolerated in older adults.     

Heart–Brain Interactions in the MR Environment: Characterization of the Ballistocardiogram in EEG Signals Collected During Simultaneous fMRI

The ballistocardiographic (BCG) artifact is linked to cardiac activity and occurs in electroencephalographic (EEG) recordings acquired inside the magnetic resonance (MR) environment. Its variability in terms of amplitude, waveform shape and spatial distribution over subject’s scalp makes its attenuation a challenging task. In this study, we aimed to provide a detailed characterization of the BCG properties, including its temporal dependency on cardiac events and its spatio-temporal dynamics. To this end, we used high-density EEG data acquired during simultaneous functional MR imaging in six healthy volunteers. First, we investigated the relationship between cardiac activity and BCG occurrences in the EEG recordings. We observed large variability in the delay between ECG and subsequent BCG events (ECG–BCG delay) across subjects and non-negligible epoch-by-epoch variations at the single subject level. The inspection of spatial–temporal variations revealed a prominent non-stationarity of the BCG signal. We identified five main BCG waves, which were common across subjects. Principal component analysis revealed two spatially distinct patterns to explain most of the variance (85% in total). These components are possibly related to head rotation and pulse-driven scalp expansion, respectively. Our results may inspire the development of novel, more effective methods for the removal of the BCG, capable of isolating and attenuating artifact occurrences while preserving true neuronal activity.