Konstantinos Simopoulos

Allergic rhinitis and aspirin-exacerbated respiratory disease as predictors of the olfactory outcome after endoscopic sinus surgery.

Background Unlike the functional outcomes of endoscopic sinus surgery, which have been thoroughly studied, the effect of the surgery on olfactory performance and the relative predictive factors have not been adequately assessed by literature. Allergic rhinitis and aspirin-exacerbated respiratory disease (AERD) are examined as potential confounding factors of the olfactory outcome in patients with extensive nasal polyposis and rhinosinusitis treated with functional endoscopic sinus surgery (FESS). Methods A population of 116 adults with severe nasal polyposis was subjected to FESS after failure of the appropriate medical treatment. The olfactory outcome was quantified by Sniffin’ Sticks at the 1st, 3rd, and 6th postoperative month in relation to the concomitant presence of allergic rhinitis (n = 62) or AERD (n = 18). Results Allergic patients seemed to perform worse than nonallergic patients at all time frames. However, when patients with similar olfactory acuity, age, and medical history are compared, allergic rhinitis does not seem to affect the postoperative improvement of the composite threshold-discrimination-identification scores. The same seems to apply for the likelihood of acquiring normosmia after surgery. On the contrary, AERD significantly limits the recovery of olfactory function at all follow-up examinations and patients with AERD are unlikely to become normosmic. Conclusion The olfactory recovery after FESS for nasal polyposis is significantly affected by the concomitant presence of AERD. Although allergy seems to have a general negative effect on olfactory acuity, it was not found to affect the extent of the olfactory improvement, when patients with comparable preoperative characteristics are addressed.

Differential Effect of Baseline Adiponectin on All-Cause Mortality in Hemodialysis Patients Depending on Initial Body Mass Index. Long-Term Follow-Up Data of 4.5 Years

OBJECTIVES We sought to investigate the interaction of adiponectin levels and body mass index (BMI) for predicting all-cause mortality in a cohort of hemodialysis (HD) patients. DESIGN Longitudinal, observational cohort study. SETTING HD unit. SUBJECTS Sixty patients (mean age: 64 ± 13 years, 39 men) with end-stage renal disease on maintenance HD followed up for 4.5 years represented the prospective study cohort. INTERVENTION Associations between baseline plasma adiponectin levels and initial BMI with all-cause mortality were assessed taking into account the assumption of nonlinear correlations. The association between adiponectin, BMI, and serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) with survival was determined cross-sectionally. MAIN OUTCOME MEASURE All-cause mortality. RESULTS Nonlinear survival modeling showed that there was a U-shaped association of BMI with all-cause mortality, whereas there was an inverse U-shaped association for plasma adiponectin levels. Using a BMI of 24 kg/m(2) as a cutoff, an interaction effect of BMI on the association between adiponectin and mortality was observed (P = .045). In participants with BMI ≥ 24 kg/m(2), each 15 μg/mL increase in plasma adiponectin levels was associated with a decreased hazard of death (hazard ratio: 0.57, 95% CI: 0.32 to 0.99) in unadjusted analysis. In HD patients with BMI < 24 kg/m(2), no significant association was observed between adiponectin and mortality (P = .989). Cross-sectional analysis showed that in the subgroup of patients in whom the protective effect of adiponectin was observed (BMI ≥ 24 kg/m(2)), a positive linear association existed between adiponectin and IL-10 levels (r = 0.345, P = .027) as well as a negative association with IL-6 levels (r = -0.322, P = .040). No association was observed in patients with BMI < 24 kg/m(2), neither with IL-10 nor with IL-6. CONCLUSIONS Obesity possibly modifies the effect of adiponectin on all-cause mortality in HD patients, thus explaining the published conflicting results in recent literature regarding the association of plasma adiponectin levels and mortality in chronic kidney disease patients.

Significance of Serum Tumor Necrosis Factor-Alpha and its Combination with Her-2 Codon 655 Polymorphism in the Diagnosis and Prognosis of Breast Cancer:

Purpose The present study was conducted to clarify the diagnostic and prognostic significance of TNF-alpha and its combination with HER-2 Ile655Val SNP in breast cancer. Methods In this case-control study, 56 consecutive patients with primary breast cancer were prospectively evaluated. The control group consisted of 45 healthy women. Serum concentrations of TNF-alpha were measured by quantitative sandwich enzyme immunoassay (ELISA). HER-2 SNP was genotyped using the PCR-RFLP method. Results Serum TNF-alpha was significantly increased in patients compared to controls. ROC analysis indicated a cutoff point of 11.00 pg/mL to classify breast cancer patients (sensitivity, 86%; specificity, 71%). Elevated TNF-alpha levels were associated with larger, poorly differentiated, invasive and advanced-stage tumors, and >3 positive lymph nodes. Regarding HER-2 SNP, patients with Ile-Val and Val-Val genotypes had significant TNF-α elevation compared with homozygous Ile-Ile patients. In multivariate analysis, high serum TNF-alpha remained an independent prognostic factor of worse overall survival; its combination with Val-Val genotype predicted a worse prognosis than high TNF-alpha alone. Conclusions Serum TNF-a could be used clinically as a useful tumor marker for diagnosis, disease extent and outcome of breast cancer. The negative impact on survival seems to be enhanced through the interaction with HER-2 Ile655Val SNP.

Epidural anesthesia followed by epidural analgesia produces less inflammatory response than spinal anesthesia followed by intravenous morphine analgesia in patients with total knee arthroplasty

Background Anesthesia and inflammatory response have been studied in major abdominal and thoracic surgical procedures, but not in major orthopaedic reconstructive procedures such as total knee arthroplasty. Most studies have compared general anesthesia with epidural anesthesia, but none has compared epidural with spinal. Material/Methods In a prospective randomized study, 2 groups of patients scheduled for total knee arthroplasty for osteoarthritis were evaluated regarding the inflammatory response to 2 types of regional anesthesia. In 30 patients (Group A) with spinal anesthesia followed by intravenous morphine analgesia, and in 26 patients (Group B) with epidural anesthesia followed by epidural analgesia, the inflammatory response was assessed through the calculation of leucocyte concentration (WBC), C-reactive protein (CRP), monocyte chemotactic protein 1 (MCP-1), interleukins (IL-1, IL-6, IL-10, IL-18), TNF-a, and leucocyte activation molecules CD11b and CD62l, in 3 blood samples (immediately before induction to anesthesia, immediately after closure of the operative wound, and at 24 hours post-operatively). Results The MCP-1 values showed a statistically significant increase (p<0.02) in the group of patients with spinal anesthesia. Of the leucocyte activation molecules, a high statistically significant increase was noticed in the expression of CD11b on monocytes in the sample taken 24 hours post-operatively in the patients of group A. Similarly, CD62l expression on neutrophils showed a high statistically significant reduction in the sample taken 24 hours post-operatively in the group of patients with spinal anesthesia compared to the group of patients with epidural anesthesia. Conclusions Our results show that epidural anesthesia followed by epidural analgesia produced less inflammatory response compared with spinal anesthesia followed by intravenous morphine analgesia in patients operated on with total knee arthroplasty, and that the most sensitive markers of those investigated were the CD11b and CD62l leucocyte activation molecules.

Corticotropin-Releasing Hormone Receptors Mediate Opposing Effects in Cholestasis-Induced Liver Cell Apoptosis

CRH receptors are expressed in human and rat liver. The current study investigated the biological role of the CRH system in the hepatocellular apoptotic process and aimed to reveal the responsible molecular mechanisms. Using a rat experimental model of common bile duct surgical ligation leading to obstructive jaundice and cholestasis, liver apoptosis was induced in the hepatic parenchyma as confirmed by the elevated expression of the early apoptotic neoepitope M30. This effect was reversed by administration of the nonselective CRH antagonist astressin but not by the selective CRH(2) antagonist astressin2B, suggesting that antagonism of the endogenous CRH(1) blocked the cholestasis-induced apoptotic mechanism. No effect was observed in the noncholestasis controls. In our experimental model, early and late apoptosis-preventing markers were induced in parallel to apoptosis; elevated gene transcript levels of the anti-apoptotic bcl-2 were found by real-time PCR in the first postoperative day and increased serum hepatocyte growth factor levels were measured by ELISA in the third postoperative day. Selective CRH(2) antagonism reversed the elevated expression of bcl-2 and hepatocyte growth factor, suggesting that this receptor type mediated antiapoptotic actions of the endogenous CRH system, opposing the preapoptotic ones mediated by CRH(1). In conclusion, the present study indicated that the CRH neuroendocrine system regulates cholestasis-induced apoptosis in the hepatic parenchyma via receptor-specific pathways. These data may contribute to better understanding of the CRH biology and its pathophysiological significance in the periphery.

The significance of p53 and bcl-2 overexpression and other prognostic factors in transitional cell carcinoma of the bladder.

The aim of this study was to investigate the expression of bcl-2 and p53 oncoproteins in a series of transitional cell bladder carcinomas and its relation to traditional prognostic indicators and patients’ survival. Specimens from 59 patients who underwent transurethral resection from March 1992 to February 1997 were included in this study. Tumors were graded based on WHO grades 1–3 and staged according to the 1997 TNM classification. Three patients lost to follow-up were excluded from the analysis. We could not establish a statistically significant relation between bcl-2 and p53 and other parameters such as sex, age, stage and grade. Tumor grade and stage were the most important factors for predicting tumor recurrence and aggressiveness. Only sex seems to significantly affect the statistics of the risk of death (p<0.05). Women had quadruple risk of death compared to men.

Urocortin and Corticotropin-Releasing Hormone Receptor Type 2 Expression in the Human Gallbladder

The corticotropin-releasing hormone (CRH) system, consisting of CRH and the homologue neuropeptide urocortin together with their receptors CRH1 and CRH2 and a specific binding protein (CRH-BP), holds the main role in mediating the response to stressful stimuli. Besides their expression in the brain, CRH peptides and receptors have been found in multiple peripheral sites. Here we investigate the expression of CRH, urocortin, CRH receptors, and CRH-BP in the wall of human normal and inflamed gallbladders, using RT-PCR and immunohistochemistry. Urocortin, but not CRH gene transcripts, was detected in RNA isolated from human gallbladder biopsy specimens. Urocortin immunoreactivity was localized in epithelial cells of the gallbladder mucosa. Gene expression of CRH2 receptor was also detected, and the receptor protein had a localization similar to that of urocortin. Finally, CRH-BP gene expression and low levels of protein immunoreactivity were also shown. There were no differences in the expression profiles of all the above molecules between normal and inflamed tissues. In conclusion, the CRH system is present in the human gallbladder, urocortin being the major ligand expressed, possibly exerting an autocrine/paracrine biological role via activation of the CRH2(α) receptors found locally. Further study is required to enfold the biological role of these effectors in gallbladder physiology and pathogenesis.

Adalimumab - an effective and promising treatment for patients with fistulizing Crohn's disease: a case series

IntroductionCrohns disease is a chronic inflammatory bowel disease of unknown etiology which may affect any part of the bowel. Fistulas are a common and often serious complication of Crohns disease. The treatment for fistulizing Crohns disease can be medical, surgical or a combination of the two. Recently, adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, has been suggested as a safe and effective treatment for the induction and maintenance of remission in adult patients with moderate to severe Crohns disease, who are refractory to conventional therapy or intolerant to infliximab. However, large studies focusing on evaluating the efficacy of adalimumab in fistulizing Crohns disease have not yet been published.Case presentationWe report the cases of three patients, of European Caucasian ethnicity and Greek nationality, with active luminal and fistulizing Crohns disease. All of the cases were treated successfully with adalimumab. Patient 1 (a 44-year-old man) and patient 2 (an 18-year-old woman) developed early post-surgical enterocutaneous fistulas, while patient 3 (a 20-year-old woman) had peri-anal fistulizing Crohns disease. Adalimumab treatment (160 mg subcutaneously at week zero, 80 mg at week two, and 40 mg every other week) was used for three different indications: (1) after the failure of other conservative medical treatments for Crohns disease (patient 1); (2) as a monotherapy in treating a naive patient (patient 2); (3) after an intolerance to infliximab (patient 3). A remission of the active luminal and fistulizing disease was achieved soon after the initiation of adalimumab and sustained thereafter with maintenance doses. No further surgical intervention was required and no adverse effects were observed in any of the cases.ConclusionsFistulizing Crohns disease remains a challenge in clinical practice. Adalimumab seems to be an effective, well-tolerated and safe treatment option for the induction and maintenance of remission in patients with moderate to severe peri-anal fistulizing Crohns disease. Furthermore, adalimumab seems to be a promising treatment option for patients with moderate to severe fistulizing Crohns disease with enterocutaneous fistulas. However, this clinical observation needs to be investigated in further clinical trials.

Does prophylactic administration of somatostatin decrease the rates of complications after pancreatic resection?: A clinical and electron microscopy study.

Objectives The postoperative morbidity after pancreatectomy remains high. The role of somatostatin and its analogs in reducing complications after pancreatic resection is controversial. The aim of the study was to evaluate the ability of somatostatin to influence pancreatic cell’s function with consequence the decrease of postoperative complications. Methods Between January 2006 and December 2009, 67 patients for which pancreatectomy was indicated were randomized into 2 groups. At surgery, biopsies of the pancreas were taken to be studied by electron microscopy and analyzed for ultrastructural morphometry. Results The total mortality was 4.4% (n = 3/67; 2 patients from the control group and 1 patient from the treatment group). The overall morbidity was 35.8% (n = 24/67). Eighteen patients in the control group (n = 18/32; 56.25%) and 6 patients in the treatment group (n = 6/35; 17.14%) developed postoperative complications (2-tailed Fisher exact test; P = 0.001). The most common complication was the presence of fistula (n = 6/67; 8.95%). Conclusions Perioperative administration of intravenous somatostatin at rates applied in this study was able to inhibit the exocrine pancreatic function. This finding supports the prophylactic effect of somatostatin on the early postoperative complications of pancreatic surgery shown in this study.

Growth of Exclusively Breastfed and Self-Weaned Children of Greece Aged 0–36 Months

OBJECTIVE Breastfeeding is recognized as an important public health issue with substantial social and economic implications. Moreover, the growth of exclusively breastfed babies differs from that of their formula-fed counterparts. The purpose of this study was to evaluate the physical growth of exclusively breastfed and self-weaned boys and girls of Greece 0-36 months of age. SUBJECTS AND METHODS The physical growth of children was monitored from birth up to 36 months of age. Body weight, length/height, and head circumference were recorded. The study population included 101 boys and 105 girls who were recruited consecutively from a private breastfeeding clinic in the second largest city of Greece and through La Leche League groups throughout the country during 2000 to 2005. All infants were exclusively breastfed for ≥ 6 months. Anthro software ( www.who.int/childgrowth/software/en/index.html ) was used to compare the data of our study population and the World Health Organization standards for weight, length/height, and head circumference for age. RESULTS Male and female infants at 12 months had almost tripled their weight (192% and 190% increase, respectively) and had increased their length (height) by 48% and 47%, respectively, and head circumference had increased by 35% and 33%, respectively. In both sexes the relative length/height and the head circumference-for-age increase rates were higher from the first to the second month of life than at any other period. CONCLUSIONS Long-term exclusively breastfed infants grow normally. Hence, no recommendations for the interruption of lactation and/or supplementation with formula are justified.