79 research outputs found

    Calcium vs. Pentagastrin Stimulation bei der C-Zell-Erkrankung der Schilddrüse : eine Matched-Pair Analyse

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    Calcitonin stimulation testing aims at defining the underlying type of c-cell disease (CCD) in order to customize appropriate timing and extent of surgery or consider observation. The importance of stimulation testing is widely accepted in hereditary CCD and the follow-up of MTC, while its role in sporadic forms is controversial. Importantly, calcium (Ca2+) stimulation testing lacks comparison to established recommendations based on reliable cut-off values using Pentagastrin (Pg). This study investigates the correlation of Ca2+- and Pg-stimulation testing in CCD. In a matched pair analysis, Pg- and Ca2+ -stimulation testing for calcitonin (Ct) was compared in 295 patients with c-cell hyperplasia (CCH) and with medullary thyroid cancer confined to the thyroid (Tx N0 M0) undergoing primary surgery.Calcitonin stimulation testing aims at defining the underlying type of c-cell disease (CCD) in order to customize appropriate timing and extent of surgery or consider observation. The importance of stimulation testing is widely accepted in hereditary CCD and the follow-up of MTC, while its role in sporadic forms is controversial. Importantly, calcium (Ca2+) stimulation testing lacks comparison to established recommendations based on reliable cut-off values using Pentagastrin (Pg). This study investigates the correlation of Ca2+- and Pg-stimulation testing in CCD. In a matched pair analysis, Pg- and Ca2+ -stimulation testing for calcitonin (Ct) was compared in 295 patients with c-cell hyperplasia (CCH) and with medullary thyroid cancer confined to the thyroid (Tx N0 M0) undergoing primary surgery

    Experimentelle und klinische Untersuchung des Einflusses von Prä- und Probiotika auf bakterielle Translokation und postoperative Infektionen nach abdominalchirurgischen Eingriffen

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    In der vorliegenden Arbeit wurde der Einfluss von Prä- und Probiotika auf bakterielle Translokation (BT) und postoperative Infektionen nach großen viszeralchirurgischen Eingriffen untersucht. Dabei wurde aus methodischen Gründen zunächst BT nach Leber- (LR) und Colonresektion (CR) allein oder in Kombination experimentell im Rattenmodell quantifiziert und deren potentielle Pathomechanismen untersucht. Anschließend wurde der Einfluss von einzelnen Probiotika und einer Kombination verschiedener Probiotika und Präbiotika auf die Inzidenz bakterieller Infektionen nach Lebertransplantation (LTX) und pyloruserhaltender Pankreaskopfresektion (PPPD) in zwei prospektiv randomisierten klinischen Studien analysiert. Im experimentellen Teil der Untersuchungen wurde BT nach LR vor allem in Leber und Milz, nach CR hauptsächlich in mesenterialen Lymphknoten (MLK) und Milz nachgewiesen. Kombination von LR und CR führte zu einer Potenzierung der BT, parallel zum Ausmaß der LR. Durch Gabe von Probiotika wurde die Konzentration von Bakterien in den MLK signifikant gesenkt. Tiere mit einer hohen coecalen Laktobazillenkonzentration hatten eine signifikant niedrigere bakterielle Konzentration in allen untersuchten Organen als Tiere mit weniger Laktobazillen. CR führten zu einer Zunahme der coecalen gramnegativen Bakterienkonzentration und zu einer Abnahme der Laktobazillen. Histologische Veränderungen der Darmmukosa wurden nicht beobachtet. Die parazelluläre Permeabilität für Ionen, nicht aber für die höhermolekulare Laktulose war im Colon in allen Gruppen im Vergleich zur Kontrollgruppe erhöht. Probiotika beeinflussten die Zusammensetzung der coecalen Flora und damit auch die BT. In der ersten klinischen Studie verminderte postoperative orale Gabe von Laktobazillus plantarum und einer ballaststoffhaltigen Ernährungslösung die Inzidenz von bakteriellen Infektionen nach LTX im Vergleich zu selektiver Darmdekontamination und ballaststofffreier Ernährung signifikant. Die Gabe von Ballaststoffen und hitzeinaktivierten Laktobazillen führte zwar auch zu einer geringen Reduktion der Infektionen; diese war jedoch nicht signifikant. In der Mehrzahl wurden enteropathogene Bakterien isoliert. Die zweite klinische Studie untersuchte den Einfluss einer Kombination von vier verschiedenen Milchsäurebakterien und vier Präbiotika auf die Inzidenz bakterieller Infektionen nach LTX und PPPD. Im Vergleich zu Präbiotika und Placebo kam es zu einer deutlichen Verminderung der Infekte, die nach LTX auch signifikant war. In beiden Studien wurde die enterale Ernährung gut vertragen mit relativ wenig Nebenwirkungen. BT tritt somit sehr häufig auch nach kleineren viszeralchirurgischen Eingriffen auf und hat organspezifisch verschiedene Ursachen. Probiotika konnten sowohl tierexperimentell die BT vermindern als auch klinisch die Inzidenz bakterieller Infektionen nach großen viszeralchirurgischen Eingriffen senken. Da sie leicht zu verabreichen sind und wenig Nebenwirkungen verursachen, könnten sie breit eingesetzt werden.In the present study, the impact of pre- and probiotics on bacterial translocation (BT) and postoperative bacterial infection rates was assessed. Due to methodological reasons, we first quantified BT following single liver (LR) and colon resection (CR) or a combination of both and analysed potential pathogenic mechanisms for BT. Then, we performed two prospective randomised clinical studies to analyse the influence of a single probiotic strain and a combination of different pre- and probiotics on the incidence of bacterial infections in patients with liver transplantation (OLT) or pylorus preserving partial pancreatoduodenectomy (PPPD). In the rat model, BT after LR mainly occurred in the liver and spleen, after CR mainly in the mesenteric lymph nodes (MLN) and spleen. BT was increased in the animals with combined operation, in parallel to the extent of liver resection. Probiotics significantly decreased the bacterial concentration in the MLN. Animals with a high cecal concentration of lactobacilli had significantly less BT than the others. CR led to an increase of cecal gramnegative bacterial concentrations and to a decrease of lactobacilli. No histological changes were observed in the intestine. Paracellular permeability for ions, but not for the larger molecule lactulose, was increased in the colon in all groups compared to the sham group. Probiotics had an influence on cecal bacterial concentration. In the first clinical study, postoperative oral administration of Lactobacillus plantarum and a fibre-enriched enteral diet significantly decreased bacterial infection rates after OLT compared to selective bowel decontamination and a fibre-free diet. Fibre and heat-inactivated Lactobacillus also led to a slight, but not significant decrease of infections. Mainly gut-derived bacteria were isolated. The second clinical study analysed the influence of a combination of four different lactic acid bacteria and fibres on bacterial infection rates after OLT and PPPD. Compared to fibres and placebo, infection rates were significantly lower after OLT and markedly lower after PPPD. In both studies, the study substances were well tolerated without serious side effects. BT even occurs following minor abdominal surgery and is caused by different mechanisms related to the kind of operation. Probiotics were able to diminish BT in the rat model as well as to decrease bacterial infection rates following major abdominal surgery in the clinical studies. As they are easy to administer and do not cause severe side effects, they could be useful in clinical practice

    Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome

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    OBJECTIVE: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. DESIGN: Cross-sectional study. METHODS: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. RESULTS: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases. CONCLUSIONS: Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete β-oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism

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    Sarah Ellis y la importancia de la educación de las jóvenes inglesas en la época victoriana

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    Together with the spread of the new evangelical movements that emerged in England in the late eighteenth and early nineteenth century, a period of redefinition of social and family ties began. Thus, gender relationships were also regulated within the framework of these reformist doctrines. Here we analyze the book titled “The Daughters of England: their position in society, character and responsibilities” by Sarah Ellis. Written in 1842, it is part of a series of texts by the same author sharing a common target: women. With a clear prescriptive profile, this handbook of conduct addressed to young ladies, describes and regulates the characteristics expected of females and the tasks to be fulfilled in terms of their social role. Using friendly and familiar language, the author aims to generate some reflection on readers in order to defend an alleged complementarity between the sexes, which restricts women’s activities to the domestic sphere.A partir de la difusión de los nuevos movimientos evangélicos que surgen en Inglaterra a fi nales del siglo XVIII y principios del XIX, comienza una etapa de resignificación de los vínculos sociales y familiares. En este sentido, las relaciones de género también encuentran su espacio de regulación dentro de estas doctrinas reformistas. El presente trabajo se propone analizar la obra The Daughters of England: their position in society, character and responsibilities, de Sarah Ellis, escrita en 1842, que forma parte de una serie de escritos de la misma autora que comparten un mismo destinatario: las mujeres.De carácter prescriptivo, este manual de conducta dirigido a las más jóvenes describe y normativiza cuáles son las características propias del sexo femenino y la tareas que este debe cumplir en función del rol social que lleva adelante.Con un lenguaje cercano y familiar, la autora pretende generar cierta reflexión por parte de sus lectoras en pos de la defensa de una supuesta complementariedad entre los sexos, que limita la presencia femenina al espacio doméstico

    Novel somatic mutations in the catalytic subunit of the protein kinase A as a cause of adrenal Cushing's syndrome: a European multicentric study.

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    Abstract CONTEXT: Somatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found in a high proportion of sporadic adenomas associated with Cushing's syndrome. The aim was to analyze the PRKACA mutation in a large cohort of patients with adrenocortical masses. METHODS: Samples from nine European centers were included (Germany, n = 4; Italy, n = 4; France, n = 1). Samples were drawn from 149 patients with nonsecreting adenomas (n = 32 + 2 peritumoral), subclinical hypercortisolism (n = 36), Cushing's syndrome (n = 64 + 2 peritumoral), androgen-producing tumors (n = 4), adrenocortical carcinomas (n = 5 + 2 peritumoral), and primary bilateral macronodular adrenal hyperplasias (n = 8). Blood samples were available from patients with nonsecreting adenomas (n = 15), subclinical hypercortisolism (n = 10), and Cushing's syndrome (n = 35). Clinical and hormonal data were collected. DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct sequencing were performed. RESULTS: PRKACA heterozygous mutations were found in 22/64 samples of Cushing's syndrome patients (34%). No mutations were found in peritumoral tissue and blood samples or in other tumors examined. The c.617A>C (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were identified: c.600_601insGTG/p.Cys200_Gly201insVal in three patients and c.639C>G+c.638_640insATTATCCTGAGG/p.Ser213Arg+p.Leu212_Lys214insIle-Ile-Leu-Arg) in one. All the mutations involved a region implicated in interaction between PKA regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed higher levels of cortisol after dexamethasone test and a smaller adenoma size, compared with nonmutated subjects. CONCLUSIONS: These data confirm and extend previous observations that somatic PRKACA mutations are specific for adrenocortical adenomas causing Cushing's syndrome
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