Zur Frage der hautlokalisationen der Lymphogranulomatose

Ohne ZusammenfassungMit 1 Textabbildung.     

Liver Damage Is Related to the Degree of Being Underweight in Anorexia Nervosa and Improves Rapidly with Weight Gain

Background: The present study investigates the relationship between hypertransaminasemia and malnutrition on the basis of a very large number of patients. We assume that the level of transaminases not only reflects the extent of underlying liver cell damage but also provides information about the metabolic situation under conditions of energy deficiency. Methods: We present an observational study in two different samples. The first sample consists of 3755 patients (mean age 22.7 years, Range 12–73 years; mean BMI 15.4 kg/m², range 8.1–25.7) out of a total of 4212 patients with anorexia nervosa treated in the Roseneck Clinic within five years for whom a complete admission laboratory was available. The second sample was obtained from a special ward for medically at-risk patients with eating disorders. During the period in question, four hundred and ten patients with anorexia nervosa were treated. One hundred and forty-two female patients (mean age 26.4 years, Range 18–63 years; mean BMI 11.5 kg/m², range 8.4–13) had a BMI of thirteen or less and a complete data set was obtained at admission and weekly in the following four weeks after admission. Results: The increase in liver transaminases shows a very high correlation with weight in sample one (N = 3755). The analysis of variance shows highly significant (<0.001) correlations with an F-value of 55 for GOT/AST and 63 for GPT/ALT. Nevertheless, the variance within the groups with the same BMI is quite high. With re-nutrition in sample two, GOT/AST decreased on average from 71 U/L to 26 U/L (MANOVA F 10.7, p < 0.001) and GPT/ALT from 88 to 41 U/L (F = 9.9, p < 0.001) within four weeks. Discussion: Below a BMI of about 13, the nutritional status of the patients becomes so critical that the energy supply of the patient is increasingly dependent on the autophagy of the liver, which can be seen in the very strong increase in transaminases here. Refeeding leads very quickly to the normalisation of the transaminases and, thus, a stabilisation of the metabolism leading also to a decrease in autophagy.     

Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway

Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical animal model that reliably recapitulates all cardinal PCOS features. We discovered that female mice prenatally treated with anti-Müllerian hormone (PAMH) display impaired sexual behavior and sexual partner preference over the reproductive age. Blunted female sexual behavior was associated with increased sexual rejection and independent of sex steroid hormone status. Structurally, sexual dysfunction was associated with a substantial loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the ventromedial nucleus of the hypothalamus (VMH) and other areas of hypothalamic nuclei involved in social behaviors. Using in vivo chemogenetic manipulation, we show that nNOS^VMH neurons are required for the display of normal sexual behavior in female mice and that pharmacological replenishment of nitric oxide restores normal sexual performance in PAMH mice. Our data provide a framework to investigate facets of hypothalamic nNOS neuron biology with implications for sexual disturbances in PCOS.

Polycystic ovary syndrome (PCOS) is a highly prevalent disease affecting 5 to 18% of women of reproductive age worldwide (1, 2). PCOS is diagnosed upon the presence of at least two out of three prime features: high circulating levels of androgens (hyperandrogenism), menstrual irregularities (oligo-anovulation), and polycystic-like ovarian morphology (2, 3). Beyond its implications leading to female infertility, the disease is associated with several metabolic disruptions, cardiovascular diseases, and psychosocial disorders (4). Among these neurological implications, it has become clear that approximately 30% or more of patients with PCOS experience sexual dysfunctions, with clinical studies reporting a high risk of low sexual arousal, desire, and satisfaction and impaired lubrication and orgasm (5–9). These symptoms allude to disturbances in brain circuits controlling sexual function in the context of PCOS.Neural circuits driving female sexual behaviors are conserved among vertebrate species operating under the influence of sex steroid hormone modulation, which is paramount for partner interaction, receptivity, and sexual performance (10, 11). Indeed, gonadal sex hormones are implicated in shaping circuit architecture in the hypothalamus during development and activating these neonatally programmed circuits over reproductive adult life in many species (12–16). The hypothalamus integrates sensorial stimuli and autonomic arousal from endogenous sex drive cues (e.g., estrous phase, energy status, hormone milieu, genital stimulation) to convey this information to other brain areas and peripheral nerves (10, 17). The ventromedial nucleus of the hypothalamus (VMH) is considered the hub of specialized neurons, with intrinsic properties driving different components of sexual behavior (18–21). The VMH harbors neurons expressing neuronal nitric oxide synthase (nNOS), the enzyme responsible for the production of nitric oxide (NO), a key gaseous neurotransmitter that stimulates female sexual behavior (22, 23) and communicates with other circuits within the social brain (24, 25). Despite current advances unraveling novel pathways in the female sexual brain with specific behavioral responses, there is a clear lack of knowledge on how disturbances in these circuits may participate in sexual dysfunctions affecting one-third of women with PCOS.Growing evidence indicates that androgen excess in utero induces a developmental reprogramming of the female fetal brain toward the manifestation of PCOS traits later in life (26–29). Some studies have suggested that the clinical signs of hyperandrogenism have detrimental sexual effects (5), indicating a negative correlation between androgen levels and sexual function in PCOS. In recent years, it has been proposed that prenatal anti-Müllerian hormone excess may trigger gestational hyperandrogenism via the inhibition of placental aromatase (29, 30) and that women with PCOS display higher circulating levels of androgens and AMH during pregnancy as compared to healthy women (29, 31). Prenatal AMH-treated mice (PAMH) reliably recapitulate all the mouse equivalents of the PCOS Rotterdam criteria (29, 32) and are thus a preclinical model to mimic the human PCOS condition. PAMH female mice also display pronounced neuroendocrine dysfunction leading to exacerbated luteinizing hormone (LH) secretion (29), as in women with PCOS (33), denoting the presence of prenatally reprogrammed defects within the gonadotropin-releasing hormone (GnRH) neuronal network. Thus, prenatal AMH excess–mediated disruptions in the female brain may be key to understanding the pathophysiology of PCOS.Here, we investigated whether prenatal AMH excess could underpin defects in sex circuits promoting sexual dysfunction in PCOS-like female mice. We uncovered a profound decrease of nNOS and progesterone receptor (PR) expression in the VMH. These anatomical changes were also associated with significant impairment of sexual receptivity in PCOS-like female mice. Nevertheless, normal sexual function in PAMH female mice was restored to control levels upon peripheral injection of NO donor. Performing a series of acute functional manipulations in freely moving female mice, we showed that chemogenetic silencing of nNOS^VMH neurons in control female mice recapitulates PCOS-like sexual dysfunctions. Taken together, we unveiled a brain pathway potentially underpinning the etiology of low sexual drive in PCOS while pointing to prospective therapeutic approaches to rescue normal sexual function in these women.     

Behavioral Health Risk Factors and Motivation to Change among Cardiovascular General Hospital Patients Aged 50 to 79 Years

Little is known about the (co-)occurrence of smoking, alcohol at-risk drinking, physical inactivity and overweight, and the motivation to change these behavioral health risk factors (HRFs) in older general hospital patients with cardiovascular disease. Between October and December 2016, all consecutively admitted patients aged 50 to 79 years were proactively recruited on 3 cardiology wards and asked to participate in a survey on HRFs and behavior change motivation. Of the eligible patients, 80.4% participated in the survey (n = 328). The mean age was 66.5 years (standard deviation 9.0), and 65.5% were male. At least 1 HRF was present in 91.8% (n = 280), at least 2 HRFs in 54.4% (n = 166), and 3 or 4 HRFs in 12.1% (n = 37) of participants. The proportion of older adults who contemplated or were changing or planning to change their behavior to meet health behavior recommendations ranged between 66.0% (smoking) and 93.2% (alcohol consumption). The results indicate a notable co-occurrence of behavioral HRFs in older patients with cardiovascular disease. The majority of older adults were at least considering changing the respective behavior. To prevent and treat diseases efficiently, hospitalization may be a suitable moment for systematic multiple HRF screening and intervention.