Do ß-Blockers Cause Depression?: Systematic Review and Meta-Analysis of Psychiatric Adverse Events During ß-Blocker Therapy.

[Figure: see text].

Eruptive Spitz nevus, a striking example of benign metastasis.

Metastasis is generally considered a characteristic of malignant tumors. Herein, we describe a patient with more than one hundred discrete Spitz nevi scattered all over her skin. Molecular analysis from three of the lesions identified a ROS1 fusion oncogene with identical genomic breakpoints, indicating that the nevi arose from a single transformed melanocyte and then disseminated throughout the integument. The demonstration of widespread distribution of a benign tumor with limited proliferative capability indicates that metastatic dissemination is not contingent on full malignant transformation. Thus, eruptive Spitz nevus is a striking example of benign metastasis, demonstrating that metastasis can occur before malignant transformation.

[A time of change for men's health: a process of increasing medicalisation?]. / Männergesundheit im Wandel: Ein Prozess nachholender Medikalisierung?

These days, men suffer from a bad reputation when the media talk about health matters. Nonetheless, talking about men's health is problematic, as it considers the health behaviour of the male gender in an essentialistic manner. Such discourse is socially under-differentiated, frequently dramatises the gender difference rather than explaining it, makes inappropriate individualisations, draws on questionable benchmarks, makes women the positive model without first reflecting, and is ahistorical. Gender patterns have a major significance for health behaviour and have indeed considerably changed the health behaviour of men and women over the last 250 years. Women have been more seriously medicalised and have, on account of their life expectancy, profited more from modernisation, developments in hygiene, the expansion of medical services and state healthcare policies. However, over the last 30 years, besides a continuing parallel medicalisation of men, signs of it increasing can also be seen. Their behaviour has become more compatible with health. A more adequate description of the situation could be achieved through a more concentrated observation of health lifestyles.

[A history of men's health--on the origin of a field of research]. / Männergesundheitsgeschichte--Zur Entstehung eines Forschungsfeldes.

This contribution traces the conditions surrounding the emergence and development of a new field of research since the millennium. It primarily presents research initiated by the Stuttgart Institute for the History of Medicine: starting with the (re)discovery of sources and the setting up of bodies of sources for a gender-sensitive, patient-oriented history of health (autobiographies, diaries, correspondence) it moves to issues such as health lifestyles, workers' masculinity, the use of medical services, health experiences during particular stages of life such as childhood or youth, as well as prevention, healthcare, mental health and the gender gap in life expectancy. In conclusion the article discusses possible theoretical frameworks and perspectives.

Switching schizophrenia patients from typical neuroleptics to aripiprazole: effects on working memory dependent functional activation.

BACKGROUND: Deficits in working memory (WM) are a core symptom of schizophrenia patients and have been linked to dysfunctional prefrontal activation, which might be caused by a mesocortical hypodopaminergic state. Aripiprazole--a partial dopamine antagonist--is a novel antipsychotic, which increases frontal dopamine concentrations in preclinical studies. However, little is known about specific medication effects on the modulation of frontal activation during WM performance. METHODS: We measured BOLD-response during a WM task in a longitudinal fMRI-study in eleven schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to aripiprazole (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. Data was analyzed with SPM5 in a 2 x 2 x 2 design (groupxsessionxtask). RESULTS: Schizophrenia patients showed fewer correct responses compared to healthy controls at T1 and a trend-wise normalization at T2. The task activated the fronto-parietal network during the contrast 2-back>0-back in all participants. At T1 patients revealed a hypoactivation in the dorsal anterior cingulate cortex (ACC), which normalized after switch to aripiprazole and correlated with improved task performance. This was due to a significant increase in the patients group while the control group did not change, as corroborated by a significant groupxtime interaction in this region. CONCLUSIONS: This study showed for the first time that the partial dopamine antagonist aripiprazole increases BOLD-signal during a WM task in the cognitive part of the ACC in schizophrenia patients, which may reflect its beneficial effect on cognitive deficits.

[A historical perspective on the health of boys and male adolescents (1780-2010)]. / Die Gesundheit von Jungen und männlichen Jugendlichen in historischer Perspektive (1780-2010).

In the discourse on health, boys are emerging as a problem group. In contrast to girls who tended to be seen as fragile if not sickly, boys used to be thought of as strong and healthy. Gender-specific concepts stipulated much more exercise for boys, the masturbation discourse prevented a relaxed relationship to the own body. The paper first describes specific problems in the biography (babies, child labour, tuberculosis, school, fitness for military service) and their solutions up to the time of the Weimar Republic. During and after the two world wars school boys tended to be of poorer health than girls. The consequences of war affect the mental health of (half-) orphans gender-non-specifically up to the third generation. After 1945, attention to health concerns is rather restricted to the professional aptitude of mining trainees, health-related risk behaviour tends to be interpreted in terms of gender. Mothers sought medical advice slightly more frequently on behalf of boys up to puberty. Concerning the time between 1780 and 2010 inferior health is often noticeable in boys and male adolescents. This used to, and still does, apply to babies, child labour, industrial work and occupational accidents, conscription and direct consequences of war. It was mostly due to gender-specific separation of labour, but partly also to a higher risk preference. The gender-specific wider scope for exercise and sports up to the 1960s, in contrast, had a health-promoting effect.

Switching schizophrenia patients from typical neuroleptics to olanzapine: effects on BOLD response during attention and working memory.

Dysfunctional activation of the dorsolateral prefrontal cortex (DLPFC) during working memory (WM) in schizophrenia patients has repeatedly been observed, however little is known about specific medication effects on the modulation of DLPFC activation. We measured activation of DLPFC during a WM task in a longitudinal fMRI study in ten schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to olanzapine (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. We analyzed the fMRI data with SPM5 in a 2 x 2 x 2 design (group x session x task). Schizophrenia patients showed fewer correct responses compared to healthy controls at both time points. The fMRI data revealed a significant group by task interaction in the bilateral DLPFC and the right parietal cortex, indicating a reduced BOLD response in the patient group. After switching to olanzapine, schizophrenia patients displayed a significant increase in the BOLD response during the 0-back condition in the DLPFC. This study showed that switching patients from conventional neuroleptics to olanzapine did not significantly alter the frontal or parietal BOLD response during working memory task. However, medication status had influences on the activation during attentional task (0-back), emphasizing the importance of baseline selection in pharmacological fMRI studies.

Samuel Hahnemann: um médico que nunca deixou de inovar / Samuel Hahnemann: a doctor who never ceased to innovate

O presente artigo aborda o caráter inovador da homeopatia, desde sua formulação inicial. Para ilustrá-lo, a autor escolhe uma série de tópicos onde Samuel Hahnemann, o fundador da homeopatia, revelou aspectos inovadores e renovadores, a saber: o modo de documentar os casos; a dinâmica da relação médico-paciente; a experimentação de medicamentos; a questão da medicação dupla e a atitude radical de continuar experimentando até o final de sua vida. Conclui-se que há evidências suficientes para se ressaltar o caráter inovador da homeopatia, aliado a uma atitude pragmática, como presentes já no trabalho pioneiro de Hahnemann.

This paper discusses the innovative nature of homeopathy since its inception. To illustrate this notion, the author chose examples showing features of both innovation and renovation in the work of Samuel Hahnemann, the founder of homeopathy: documentation of cases; dynamics of the doctor-patient relationship; experimentation of medicines; double medication and the radical attitude of experimenting until the end of his life. It is concluded that there is sufficient evidence supporting the innovative nature of homeopathy, associated to elements of pragmatism, as already noticeable in Hahnemann’s pioneer work.

Glutamine's protection against cellular injury is dependent on heat shock factor-1.

Glutamine (GLN) has been shown to protect cells, tissues, and whole organisms from stress and injury. Enhanced expression of heat shock protein (HSP) has been hypothesized to be responsible for this protection. To date, there are no clear mechanistic data confirming this relationship. This study tested the hypothesis that GLN-mediated activation of the HSP pathway via heat shock factor-1 (HSF-1) is responsible for cellular protection. Wild-type HSF-1 (HSF-1(+/+)) and knockout (HSF-1(-/-)) mouse fibroblasts were used in all experiments. Cells were treated with GLN concentrations ranging from 0 to 16 mM and exposed to heat stress injury in a concurrent treatment model. Cell viability was assayed with phenazine methosulfate plus tetrazolium salt, HSP-70, HSP-25, and nuclear HSF-1 expression via Western blot analysis, and HSF-1/heat shock element (HSE) binding via EMSA. GLN significantly attenuated heat-stress induced cell death in HSF-1(+/+) cells in a dose-dependent manner; however, the survival benefit of GLN was lost in HSF-1(-/-) cells. GLN led to a dose-dependent increase in HSP-70 and HSP-25 expression after heat stress. No inducible HSP expression was observed in HSF-1(-/-) cells. GLN increased unphosphorylated HSF-1 in the nucleus before heat stress. This was accompanied by a GLN-mediated increase in HSF-1/HSE binding and nuclear content of phosphorylated HSF-1 after heat stress. This is the first demonstration that GLN-mediated cellular protection after heat-stress injury is related to HSF-1 expression and cellular capacity to activate an HSP response. Furthermore, the mechanism of GLN-mediated protection against injury appears to involve an increase in nuclear HSF-1 content before stress and increased HSF-1 promoter binding and phosphorylation.

Effects of total body irradiation and cyclosporin a on the lethality of toxic shock syndrome toxin-1 in a rabbit model of toxic shock syndrome.

Toxic shock syndrome (TSS) may be mediated by superantigen-activated T cells, a theory we tested in rabbits, which are more susceptible to the lethal effects of superantigens, such as TSS toxin-1 (TSST-1), than are mice. Rabbits exposed to 10 cGy of total body irradiation exhibited T cell deficiency, with profound depletion of splenic lymphocytes and circulating CD4(+) lymphocytes, as well as an inability to manifest delayed-type hypersensitivity. Nevertheless, these rabbits remained completely susceptible to TSST-1, indicating that TSS can occur in the setting of marked immunosuppression.

Functional analysis of the TCR binding domain of toxic shock syndrome toxin-1 predicts further diversity in MHC class II/superantigen/TCR ternary complexes.

Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHC class II molecules on APCs and with particular variable regions of the TCR beta-chain (Vbeta). To further define the interface between the bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within the putative TCR binding region of TSST-1 along the central alpha helix adjacent to the N-terminal alpha helix and the beta7-beta9 loop as well as with two universally conserved SAG residues (Leu(137) and Tyr(144) in TSST-1). Mutants were analyzed for multiple functional activities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues (Gly(16), Trp(116), Glu(132), His(135), Gln(136), and Gln(139)), each individually critical for functional activity as well as direct interaction with the human TCR Vbeta2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, a model of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3 loop of Vbeta2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vbeta specificity of TSST-1.

Da utilidade da história da Homeopatia: aspectos de sua pátria de origem / About the usefuliness of the history of homeopathie: aspects of its origin country

O autor aborda aspectos da origem da Homeopatia na Alemanha e ressalta a importância do saber histórico para a compreensäo da atualidade