Faktori rizika za nastanak postoperativnog ileusa kod elektivnih resekcija debelog creva

Postoperative ileus is an inevitable postoperative event, multifactorial in origin. If it extends longer than expected it can seriously interfere with recovery. The aim of this prospective study was to identify risk factors for development of postoperative ileus (POI) in homogenous cohort of patients with cancer of the large bowel treated with standardized protocol by the same surgical team. The role of inflammation as response to surgical trauma in relation to POI was also analyzed. Study included 103 patients scheduled for open colorectal resection for cancer without evidence of metastatic disease. Primary outcome measure was POI according to strict definition. To identify potential risk factors for POI apart from patients’ characteristics, various parameters were recorded in the pre-, intra- and postoperative period. Inflammatory response was measured with: PCT, CRP, IL-6, SE, albumin, fibrinogen, transferin, feritin, and CRP in peritoneal fluid. These parameters were correlated with intraoperative variables such as: incision length, duration of surgery, duration of bowel exposition, adhesiolysis, intraoperative contamination and estimated blood loss. Postoperative complications were graded according to Clavien and Dindo. The association between POI and recorded variables were studied using univariate and multivariate analyses. The rate of POI was 11.3%. None of the preoperatively recorded parameters had influence on development of POI. Among intraoperative parameters in univariate regression analysis: incision length (OR=1.200; p=0.017), volume of crystalloids (OR=1.001; p=0.025) and total opiate dose (OR=1.095; p=0.008) were associated with POI. Postoperative variables that showed statistical significance were: SE on day 1 (OR=1.051; p=0.012) and sodium on day 1 (OR= 0.815, p=0.032). Length of incision (OR=1.408; p=0.025) and sodium (OR=0.701; p=0.016) were the only independent risk factors for the development of POI according to multivariate analysis. Although studies show that inflammation is one of the main mechanisms for development of POI, apart from sedimentation rate none of the inflammatory parameters showed as reliable marker for this complication. Identification of patients at risk for development of POI could allow clinicians to influence on modifiable risk factors and to develop strategies to enhance recovery in this group of patients. According to results obtained in this study patients who develop POI have increased risk for reoperation, and longer hospital stay

Prenatal Glucocorticoids: Short-Term Benefits and Long-Term Risks

Glucocorticoids are steroid hormones synthesized in the adrenal gland cortex, and most of their physiological effects are mediated by the glucocorticoid receptor (GR), that acts as a ligand-dependent transcription factor. Coordinate changes in metabolism under glucocorticoid influence provide energy that is instantly and selectively available to vital organs, an enables them to deal with immediate environmental demands, at the expense of anabolic pathways, such as bone formation, reproduction, immunological responses and other, that are being blunted or delayed, under glucocorticoid influence [1-3]. During fetal development the synthesis of adrenal glucocorticoids precedes the establishment of a definitive structure of the gland. In rats, secretion of the main glucocorticoid – corticosterone starts as early as on day 13 of development [4] (term=22 days, short gestation period), while in humans secretion of the main glucocorticoid – cortisol starts in the 8th week of pregnancy (term=40 weeks, long gestation period) [5]. Glucocorticoid receptor mRNA is present in the tissue derivatives of all three germ layers from fetal day 13 onwards, and increases gradually during rat fetal development [6]. Human fetal tissues express GR at the gestational age of 6 weeks, meaning that the machinery for hormone action is prepared at the early stages of development [5]. These facts suggest that endogenous glucocorticoids produced by the fetal adrenal glands have a crucial role in fetal growth and the development of individual fetal tissues [7]. In response to the prepartum rise in glucocorticoids a wide variety of changes known as “preparation for birth” occurs, meaning that the maturational changes in many fetal tissues, essential for neonatal survival, are intensified during the last third of gestation. Namely, circulating glucocorticoids induce fetal lung maturation and surfactant production, trigger a variety of physiological effects on brain cell differentiation and synaptogenesis, stimulate the production of hepatic gluconeogenic enzymes, affect pancreatic -cell development and insulin content, influence renal development and affect the maturation of the immune system [8-10]. Metabolic, cardiovascular and immune adaptations under glucocorticoid influence are fundamental to successfully overcoming birth-related stress and postnatal adaptation of the newborn to environmental challenges [11, 12]. Environmental conditions influence the prevailing nutritional and endocrine status in mothers and fetuses. Numerous animal and human studies have shown that adverse environmental conditions during pregnancy, such as maternal undernutrition [13, 14], stress [15, 16], illness, placental insufficiency [17, 18], as well as prenatal glucocorticoid exposure [19, 20] affect fetal development and postnatal outcome. Changes in the maternal hypothalamic-pituitary-adrenal (HPA) activity, transplacental diffusion of nutrients, hormones and growth factor supply, potently affect the fetal HPA axis influencing glucocorticoid output as well as other developing systems [21, 22]. Gestational age, at which an insult occurs, its nature and intensity, determines the specific tissue or organ which will be affected by the insult. Glucocorticoids are the key mediators between maternal environment and the fetus, and as such are involved in adaptations of the fetus to predicted postnatal environment. Even transient changes in glucocorticoid levels could have longlasting consequences. The outcome might be growth retardation and change in the developmental trajectory, in the direction that best suited to the expected environment [23, 24]. This phenomenon is known as programming. The adaptations caused by suboptimal intrauterine conditions are appropriate if the predicted and actual postnatal environments match, and lead to survival to reproduce in a deprived environment [25, 26]. If there is a mismatch between the environment predicted and the actual environment experienced postnatally, adaptations are inappropriate and result in the development of disease like hypertension, ischemic heart disease, glucose intolerance, insulin resistance and type 2 diabetes [27-29]. In this chapter the latest findings, with clear statements from the literature, as well as own results regarding the endocrine mechanisms of intrauterine programming mediated by glucocorticoids will be analyzed. The causal relationship between a prenatally programmed endocrine axes and their postnatal functioning that affect growth, stress response, metabolism and reproduction will be discussed. In order to better understand mechanisms of fetal glucocorticoid programming of endocrine axes, special attention will be paid to key points of their development

Failures and complications of thoracic drainage

Background/Aim. Thoracic drainage is a surgical procedure for introducing a drain into the pleural space to drain its contents. Using this method, the pleura is discharged and set to the physiological state which enables the reexpansion of the lungs. The aim of the study was to prove that the use of modern principles and protocols of thoracic drainage significantly reduces the occurrence of failures and complications, rendering the treatment more efficient. Methods. The study included 967 patients treated by thoracic drainage within the period from January 1, 1989 to June 1, 2000. The studied patients were divided into 2 groups: group A of 463 patients treated in the period from January 1, 1989 to December 31, 1994 in whom 386 pleural drainage (83.36%) were performed, and group B of 602 patients treated form January 1, 1995 to June 1, 2000 in whom 581 pleural drainage (96.51%) were performed. The patients of the group A were drained using the classical standards of thoracic drainage by the general surgeons. The patients of the group B, however, were drained using the modern standards of thoracic drainage by the thoracic surgeons, and the general surgeons trained for this kind of the surgery. Results. The study showed that better results were achieved in the treatment of the patients from the group B. The total incidence of the failures and complications of thoracic drainage decreased from 36.52% (group A) to 12.73% (group B). The mean length of hospitalization of the patients without complications in the group A was 19.5 days versus 10 days in the group B. The mean length of the treatment of the patients with failures and complications of the drainage in the group A was 33.5 days versus 17.5 days in the group B. Conclusion. The shorter length of hospitalization and the lower morbidity of the studied patients were considered to be the result of the correct treatment using modern principles of thoracic drainage, a suitable surgical technique, and a careful follow-up of the patients

Inhibitory effect of SRIH-14 on ACHT cells in neonatal female rats

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Neonataly applied SRIH-14 has immediate and prolonged inhibitory effect on pituitary GH cells

The immediate and prolonged effects of neonatal SRIH-14 treatment on pituitary somatotrophs (GH) were investigated. Female rats were injected s.c. twice a day with 20 _g of SRIH-14/100g b.w., for five consecutive days (from 3rd to 7th day of life). Animals were sacrificed at different life periods: at neonatal (8th day), juvenile (16th day), peripubertal (38th day) and adult (80th day) period of life. GH cells were studied using the peroxidase-antiperoxidase immunocytochemical procedure. Morphometry and stereology were used to evaluate changes in the number of GH-immunoreactive cells per unit area, their volume and volume density. After SRIH-14 treatment, the most prominent decrease of all measured parameters was observed in the neonatal period. SRIH-14 induced a significant decrease of GH cell volumes and volume densities in the juvenile, peripubertal and adult periods of life. The number of GH-positive cells was significantly decreased when examined immediately after treatment, but significantly increased in adult females. Body weight, absolute or relative pituitary weights were not affected in any of the examined age groups. These findings suggest that neonatal SRIH-14 treatment exerts a significant immediate and prolonged inhibitory effect on GH cells, but does not affect the growth rate in female rats.Ispitivan je neposredan i odložen efekat neonatalnog tretmana somatostatinom (SRIH-14) na somatotropne (GH) ćelije. Ženke pacova su dva puta dnevno s.c. tretirane sa 20 _g SRIH-14/100g t.m. u toku pet dana (od 3. do 7. dana života) i žrtvovane u različitim periodima života: u neonatalnom (8. dan) juvenilnom (16. dan), peripubertalnom (38. dan) i adultnom (80. dan) periodu. GH ćelije su imunocitohemijski obeležene metodom peroksidaza-antiperoksidaza a morfometrijskim i stereološkim metodama određivani su broj GH ćelija po jedinici površine, njihov volumen i volumenska gustina. Nakon somatostatinskog tretmana, najznačajnije smanjenje svih merenih parametara utvrđeno je u neonatalnom periodu. SRIH-14 je izazvao značajno smanjenje volumena i volumenske gustine GH ćelija u juvenilnom, peripubertalnom i adultnom periodu života. Broj GH-pozitivnih ćelija po mm2 je bio značajno smanjen kada je ispitivan neposredno nakon tretmana, ali je bio značajno povećan kod adultnih ženki. Telesna masa, kao i apsolutne i relativne mase hipofiza nisu bile izmenjene ni u jednoj od ispitivanih starosnih grupa. Dobijeni rezultati ukazuju da neonatalni tretman somatostatinom izaziva značajan neposredan i odložen inhibitoran uticaj na GH ćelije, ali ne utiče na stopu rasta kod ženki pacova.nul

Pituitary ACTH cells in female rats after neonatal treatment with SRIH-14.

The prolonged effects of neonatal SRIH-14 treatment on pituitary ACTH cells were investigated. Neonatal female rats were injected subcutaneously with SRIH (20 microg/100g b.w.) every 12 hours for five consecutive days (3rd-7th day of life). Groups of rats were then killed at the juvenile (16th day), peripubertal (38th day) or adult (80th day) stage. ACTH cells were visualized using the peroxidase-antiperoxidase immunocytochemical procedure. Morphometry and stereology were used to evaluate the ACTH-immunoreactive cell volume and volume density. The histological and immunocytochemical characteristics of ACTH cells in neonatally treated females were changed in all examined periods. Thus, SRIH-14 induced significant (

ONE HUNDRED YEARS OF MILES’ OPERATION- WHAT HAS CHANGED?

Lisfranc was probably the first to excise the rectum for cancer. He performed operation using perineal approach in 1826. This operation came into common use fifty years later. Czerny did the first combined abdominoperineal resection in attempt to finish excision he could not complete from below. Some fifteen years later Ernest Miles described the planned, one stage abdominoperineal resection.Miles name has become a synonym for this combined procedure, creating a radical change in the philosophy of resection and en bloc lymphadenectomy.In the beginning of twenty-century abdominoperineal resection became golden standard in the treatment of rectal cancer. Reconstructive operations, introduction of stapling devices and better understanding of potential tumor spread, reduced indications for Miles operation.Surgical treatment of rectal cancer made progress in the past 100 years. Miles was the first in line. Without his theory of perirectal lymphatic spread recurrence rate would be still as high as 95%

8-Iso-prostaglandin F2α as a potential biomarker in patients with unipolar and bipolar depression

Objective: Previous studies have shown that the disturbance of redox homeostasis plays a role in the pathogenesis of mood disorders. It is currently unclear whether oxidative stress parameters can be used as biomarkers (state vs. trait). The aim of the present study was to investigate oxidative stress markers in patients with major depressive disorder (MDD) and bipolar disorder (BP) in acute depressive episodes and remission, and healthy individuals. Patients and methods: Thirty-two patients with a diagnosis of MDD, 32 patients with a diagnosis of BP and 32 matched healthy controls were included in the study. We measured the serum levels of markers of oxidative damage, including 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-Iso-prostaglandin F2α (8-iso-PGF2α; 8-isoprostane), and malondialdehyde (MDA), and also serum activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) in both acute and remission phase, and in control group. Results: After controlling for the effects of age, sex, body mass index, and smoking status, serum 8-iso-PGF2α levels were significantly higher in both patient groups compared to controls, regardless of disease phase. The activities of GPX and GR were significantly lower in the acute phase in MDD patients compared to controls. Serum GR activity was lower in both acute and remission phase in MDD compared to BP. Conclusions: Our results suggest that both MDD and BP are associated with a disturbed redox balance with a particularly pronounced increase in serum 8-iso-PGF2α levels in both groups and the presence of glutathione metabolism disorders in MDD patients. Further research is needed to confirm the importance of oxidative stress parameters as potential biomarkers of MDD and BP

Development of pituitary ACTH and GH cells in near term rat fetuses

This study describes the development of ACTH and GH cells in 19- and 21-day-old rat fetuses using immunohistochemistry and morphometric measurements. Between days 19 and 21 of pregnancy, the total volume of fetal ACTH cells was unchanged, while their volume density and number per unit of area decreased significantly. ACTH-like immunopositivity in the pars intermedia increased during the examined period. The cell volume, volume density and number of GH cells per unit of area all markedly increased in parallel with fetal development, i.e., from gestational days 19 to 21. GH-like immunopositivity is demonstrated in the pars intermedia of 21-day-old fetuses for the first time.Prezentovano istraživanje opisuje razvoj ACTH i GH ćelija hipofize fetusa pacova, neposredno pred rođenje korišćenjem imunohistohemije i morfometrijskih merenja. Od 19. do 21. dana gestacije volumen ACTH ćelija fetusa bio je nepromenjen, dok su volumenska gustina i broj ćelija po jedinici površine značajno smanjeni. Intenzitet ACTH imunopozitivnosti u pars intermedia povećavn je tokom ispitivanog perioda. Volumen GH ćelija, volumenska gustina i brojnost po jedinici površine značajno su povećani tokom završnog perioda fetalnog razvoja, tj. od 19. do 21. dana gestacije. GH imunopozitivnost prvi put je demonstrirana u ćelijama pars intermedia kod fetusa starih 21 dan.nul