Left prefrontal intermittent theta burst stimulation ameliorates tinnitus distress and symptoms of depression - A feasibility study.

Tinnitus remains a notoriously difficult to treat clinical entity. 1-2% of the entire population report relevant emotional distress due to tinnitus, and causal treatments are lacking. Repetitive transcranial magnetic stimulation (rTMS), most commonly of auditory cortical areas, has shown mixed results in the past. Prefrontal rTMS, including intermittent theta burst stimulation (iTBS) has shown more promising results in the treatment of depression, and clinical data suggests a meaningful overlap between tinnitus and depression. Therefore, we performed a feasibility study of 28 consecutive patients with tinnitus treated with an iTBS protocol over the left dorsolateral prefrontal cortex for three weeks. After treatment, we observed significant ameliorations of tinnitus distress as measured by the Tinnitus Handicap Inventory Questionnaire (THI), the Tinnitus Functional Index (TFI), the Mini-Tinnitus Questionnaire (Mini-TQ) and also of depression as measured by the Major Depression Inventory (MDI). Effect sizes were small to moderate and short-lived. Treatment response rates, defined as improvement of the THI of at least 7 points, were 35.7%. At follow-up twelve weeks after end of treatment, severity of tinnitus and depression returned to approximately baseline level on a descriptive level. Amelioration of depressive symptoms correlated only with TFI change, but not that of other measures of tinnitus distress. The data suggest that a prefrontal iTBS protocol might be applied in the treatment of tinnitus and open avenues for future neurostimulatory treatments other than those of auditory regions.

Treatment of depression and borderline personality disorder with 1 Hz repetitive transcranial magnetic stimulation of the orbitofrontal cortex - A pilot study.

Borderline personality disorder (BPD) is characterised by impairments in emotional regulation, impulse control and interpersonal interaction. Comorbid depression is common. The orbitofrontal cortex (OFC) plays a crucial role in the biological substrate of BPD. We investigated the effects of 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting the OFC on depressive symptoms and symptoms of BPD in 15 patients suffering from both conditions to assess feasibility and effectiveness. Target treatment intensity was 120% of resting motor threshold (RMT) and intended duration four weeks. Treatment improved both symptoms of depression as measured by the Hamilton Depression Rating Scale and of BPD as measured by Borderline Symptom List-23 and Barratt Impulsivity Scale. Drop-out rates were high with 7/15 patients not completing the full course of rTMS, but only two drop-outs were related to treatment. Only a minority of patients tolerated target treatment intensity. Despite the limitations, the results suggest efficacy of treatment and welcome further research.

Mechanisms of chemical-induced innate immunity in allergic contact dermatitis.

Allergic contact dermatitis (ACD) is one of the most prevalent occupational skin diseases and causes severe and long-lasting health problems in the case of chronification. It is initiated by an innate inflammatory immune response to skin contact with low molecular weight chemicals that results in the priming of chemical-specific, skin-homing CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 cells. Following this sensitization step, T lymphocytes infiltrate the inflamed skin upon challenge with the same chemical. The T cells then exert cytotoxic function and secrete inflammatory mediators to produce an eczematous skin reaction. The recent characterization of the mechanisms underlying the innate inflammatory response has revealed that contact allergens activate innate effector mechanisms and signalling pathways that are also involved in anti-infectious immunity. This emerging analogy implies infection as a potential trigger or amplifier of the sensitization to contact allergens. Moreover, new mechanistic insights into the induction of ACD identify potential targets for preventive and therapeutic intervention. We summarize here the latest findings in this area of research.

Mouse granzyme K has pro-inflammatory potential.

Granzymes (gzms) are key components of T-killer (Tc) cells believed to mediate pro-apoptotic activities. Recent evidence suggests that gzms also possess non-cytotoxic activities that contribute to host defense. In this study, we show that Tc cells from lymphocytic choriomeningitis virus (LCMV)-infected wild-type (wt) and gzm A/B-deficient mice express similar levels of gzmK protein, with both mouse strains efficiently controlling infection. GzmK, in recombinant form or secreted by ex vivo-derived LCMV-immune gzmAxB(-/-) Tc cells, lacks pro-apoptotic activity. Instead, gzmK induces primary mouse macrophages to process and secrete interleukin-1ß, independent of the ATP receptor P2X(7). Together with the finding that IL-1Ra (Anakinra) treatment inhibits virus elimination but not generation of cytotoxic Tc cells in wt mice, the data suggest that Tc cells control LCMV through non-cytotoxic processes that involve gzmK.

Ovarian dysgerminoma: a retrospective analysis of results of treatment, sites of treatment failure, and radiosensitivity.

Thirty-five patients with a diagnosis of pure ovarian dysgerminoma underwent assessment at our institution between 1950 and 1984. The median age of these patients was 21 years (range, 8 to 41 years). The surgical pathologic stages of the tumors were as follows: stage IA1 in 18 patients, stage IA2 in 2, stage IB1 in 2, stage IC in 1, stage IIB in 2, stage III in 9, and stage IV in 1. The overall survival at 5, 10, and 20 years was 94.3%, 82.9%, and 82.9%, respectively, for all 35 patients and 100%, 83.9%, and 83.9%, respectively, for the 18 patients with stage IA1 lesions. The maximum interval from diagnosis to relapse was 3.7 years. All patients were under surveillance for a minimum of 2 years (median follow-up, 15.9 years). Of the 18 patients with stage IA1 disease, 16 did not receive prophylactic radiation therapy to the para-aortic lymph nodes, and in 6 of the 16 (38%) recurrent disease developed in this region. Five of these patients were salvaged with radiation therapy and one with radiation therapy and subsequent chemotherapy. No definite correlation was noted between the size or mass of the resected unilateral encapsulated tumor and the risk of development of recurrent disease. For patients with stage IA1 dysgerminoma who have undergone unilateral oophorectomy, two treatment options seem reasonable: (1) observation, with radiation therapy reserved for subsequent recurrence, or (2) prophylactic radiation therapy (2,000 cGy) to para-aortic and ipsilateral common iliac lymph nodes, which would preserve fertility.