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Worldwide, thyroid cancer accounts for some 10% of total cancer incidence, most markedly for females. Thyroid cancer radiotherapy, typically using 131I (T1/2 8.02 days; β− max energy 606 keV, branching ratio 89.9%), is widely adopted as an adjunct to surgery or to treat inoperable cancer and hyperthyroidism. With staff potentially receiving significant doses during source preparation and administration, radiation protection and safety assessment are required in ensuring practice complies with international guidelines. The present study, concerning a total of 206 patient radioiodine therapies carried out at King Faisal Specialist Hospital and Research Center over a 6-month period, seeks to evaluate patient and occupational exposures during hospitalization, measuring ambient doses and estimating radiation risk. Using calibrated survey meters, patient exposure dose-rate estimates were obtained at a distance of 30-, 100- and 300 cm from the neck region of each patient. Occupational and ambient doses were measured using calibrated thermoluminescent dosimeters. The mean and range of administered activity (AA, in MBq) for the thyroid cancer and hyperthyroidism treatment groups were 4244 ± 2021 (1669–8066), 1507.9 ± 324.1 (977.9–1836.9), respectively. The mean annual occupational doses were 1.2 mSv, that for ambient doses outside of the isolation room corridors were found to be 0.2 mSv, while ambient doses at the nursing station were below the lower limit of detection. Exposures to staff from patients being treated for thyroid cancer were less compared to hyperthyroidism patients. With a well-defined protocol, also complying with international safety requirements, occupational exposures were found to be relatively high, greater than most reported in previous studies.

Medical exposure of the general population due to radiological investigations is the foremost source of all artificial ionising radiation. Here, we focus on a particular diagnostic radiological procedure, as only limited data are published with regard to radiation measurements during urethrograpic imaging. Specifically, this work seeks to estimate patient and occupational effective doses during urethrographic procedures at three radiology hospitals. Both staff and patient X-ray exposure levels were calculated in terms of entrance surface air kerma (ESAK), obtained by means of lithium fluoride thermoluminescent dosimeters (TLD-100(LiF:Mg:Cu.P)) for 243 urethrographic examinations. Patient radiation effective doses per procedure were estimated using conversion factors obtained from the use of Public Health England computer software. In units of mGy, the median and range of ESAK per examination were found to be 10.8 (3.6-26.2), 7.0 (0.2-32.3), and 24.3 (9.0-32.0) in Hospitals A, B, and C, respectively. The overall mean and range of staff doses (in µGy) were found to be 310 (4.0-1750) per procedure. With the exception of hospital C, the present evaluations of radiation dose have been found to be similar to those of previously published research. The wide range of patient and staff doses illustrate the need for radiation dose optimisation.

Purpose:To compare tumour dose distribution, conformality, homogeneity, normal tissue avoidance, tumour control probability (TCP) and normal tissue complication probability (NTCP) using 3D conformal radiation therapy (3DCRT), 3- and 4-field intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with locally advanced rectal cancer.Materials and methods:Twenty-four patients staged T1–3N+M0 with locally advanced rectal cancer underwent neoadjuvant chemoradiation therapy. Four different radiotherapy plans were prepared for each patient: 3DCRT, 3- and 4-field IMRT and VMAT are evaluated for target distribution using CI and homogeneity index (HI), normal tissue avoidance using Dmax, V45, V40, V50 and TCP and NTCP using the Lyman–Kutcher–Burman model.Results:VMAT has better HI (HI = 1·32) and 3DCRT exhibited better conformality (CI = 1·05) than the other radiotherapy techniques. With regard to normal tissue avoidance, all radiotherapy plans met the constraints. Dmax in the 3DCRT plans was statistically significant (p = 0·04) for bladder and no significant differences in V40 and V50. In the bowel bag, no significant differences in Dmax for any radiotherapy plan and V40 was lower in 3DCRT than VMAT (p = 0·024). In the case of femoral heads, 3DCRT has a statistically significant lower dose on Dmax than 4-field IMRT (p = 0·00 « 0·05). VMAT has the biggest TCP (80·76%) than the other three radiotherapy plans. With regard to normal tissue complications, probabilities were shown to be very low, of the order of 10-14 and 10-41 for bowel bag and femoral heads respectively.Conclusions:It can be concluded that 3DCRT plan improves conformity and decreases radiation sparing in the organ at risks, but the VMAT plan exhibits better homogeneity and greater TCP.

Differentiated thyroid cancer (DTC) represents the vast majority of all thyroid cancers, with the papillary variant being the most common. According to the previous 2009 American Thyroid Association (ATA) guidelines, papillary thyroid microcarcinoma (PTMC; ≤1 cm in diameter) exhibiting cervical lymph node metastasis corresponded to an intermediate-risk group for recurrence or metastasis. However, the latest 2015 ATA guidelines advocate that a patient with PTMC is low-risk if there are ≤5 regional node micrometastases. This means that therapeutic radioactive iodine (RAI) is not required. The current study reports a rare case of a patient who underwent total thyroidectomy due to multi-nodular goiter where the pathologic specimen exhibited two PTMC foci in regional lymph nodes, but no primary cancer was identified in the thyroid despite thorough examination of the thyroid parenchyma. The etiology of such results is unknown and it was hypothesized that it may be the consequence of insufficient pathologic examination or due to the regression of a primary PTMC in the thyroid. Moreover, the risk-stratification of cases with intra-lymph node PTMC without any evidence of primary cancer in the thyroid is not considered in the ATA recommendations. The aim of the current report was to elucidate the risk-stratification of this rare occurrence and to reconsider the possible etiologies. By extrapolating the latest ATA recommendations concerning a patient with a known primary PTMC and ≤5 metastatic micro-foci (thus the only difference between cases being the absence of a primary tumor), it was concluded that the patient should be considered low-risk. As a consequence, RAI therapy should be deemed as unnecessary despite the presence of lymph node microfoci. Moreover, it was proposed that cervical lymph node PTMC with no evidence of a primary tumor in the thyroid could be the consequence of normal thyroid tissue micro-deposit progression to cancer within the lymph node, which is a rare benign entity.

The purpose of the present study is to examine the diagnostic and predictive accuracy of the thyroglobulin (Tg) to thyroid stimulating hormone (TSH) and TSH/Tg ratios in normothyroid patients with differentiated thyroid cancer (DTC). We conducted a retrospective cohort study evaluating the diagnostic accuracy of the serum Tg/TSH and TSH/Tg ratios in normothyroid patients with thyroid nodules. We also systematically searched the international literature using the Medline, Cochrane’s CENTRAL, Scopus, Clinicaltrials.gov, EMBASE, and Google Scholar databases for evidence concerning the diagnostic and predictive accuracy of these ratios. Overall, 374 patients were identified in our cohort study of whom 240 were treated for benign disease and 134 were treated for DTC. Significant differences were noted in the Tg/TSH and TSH/Tg values among cases with malignant and benign disease (P=0.020). However, the diagnostic ROC curve did not confirm these results (Tg/TSH=0.572 and TSH/Tg=0.428). After searching the international literature, we identified 8 studies. The majority of the included data reported significant differences among patients with benign/malignant disease and those with successful iodine therapy compared to those with disease relapse. However, the clinical relevance was clearer among studies that investigated the usefulness of these ratios in predicting recurrent disease. The findings of our study support that the Tg/TSH ratio increases in patients with DTC and can, thus, become useful in the future as a predictive marker of ablative 131I therapy success. However, given the significant variability of Tg its diagnostic accuracy remains to date minimal; thus, the actual cut-off value that can be used to discriminate cancer cases from benign disease has not been determined yet.

Most of the acute ischemic events, such as acute coronary syndromes and stroke, are attributed to vulnerable plaques. These lesions have common histological and pathophysiological features, including inflammatory cell infiltration, neo-angiogenesis, remodelling, haemorrhage predisposition, thin fibrous cap, large lipid core, and micro-calcifications. Early detection of the presence of a plaque prone to rupture could be life-saving for the patient; however, vulnerable plaques usually cause non-haemodynamically significant stenosis, and anatomical imaging techniques often underestimate, or may not even detect, these lesions. Although ultrasound techniques are currently considered as the "first-line" examinations for the diagnostic investigation and treatment monitoring in patients with atherosclerotic plaques, positron emission tomography (PET) imaging could open new horizons in the assessment of atherosclerosis, given its ability to visualize metabolic processes and provide molecular-functional evidence regarding vulnerable plaques. Moreover, modern hybrid imaging techniques, combining PET with computed tomography or magnetic resonance imaging, can evaluate simultaneously both functional and morphological parameters of the atherosclerotic plaques, and are expected to significantly expand their clinical role in the future. This review summarizes current research on the PET imaging of the vulnerable atherosclerotic plaques, outlining current and potential applications in the clinical setting.

Objective Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the thyroid gland is a rare indolent malignant disease encountered in approximately 0.5% of patients with Hashimoto thyroiditis (HT). The purpose of the present systematic review was to accumulate the current evidence in the field. Study design We searched the Medline, Scopus, EMBASE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials CENTRAL databases from inception to May 2018. Statistical analysis was performed with SPSS version 22.0. Results Fourteen case series and 20 case reports were finally included in the present systematic review. Analysis of the patient data included in the published case reports suggested that the age at diagnosis of MALT lymphoma does no differ among males and females (64 [52.5-73] vs. 67 [60.5-72] years, p = 0.442). HT was detected in 60% of patients, whereas coexisting carcinoma was evident in 17% of cases. The incidence of HT and thyroid cancer was comparable among males and females (p = 0.474 and p > 0.999, respectively). Among all patients included in the present systematic review there were two disease relapses and two deaths attributed to the disease. Conclusion MALT lymphoma of the thyroid gland is a rare malignancy with an indolent course. The scarce data available in the literature preclude safe conclusions concerning the mode of treatment and follow-up of these patients. However, the combination of minimally invasive surgery and adjuvant therapy seems feasible. Moreover, an extended follow-up period is recommended.

BACKGROUND Lutetium-based scintillators with high-performance electronics introduced time-of-flight (TOF) reconstruction in the clinical setting. Let G' be the total signal to noise ratio gain in a reconstructed image using the TOF kernel compared with conventional reconstruction modes. G' is then the product of G1 gain arising from the reconstruction process itself and (n-1) other gain factors (G2, G3, … Gn) arising from the inherent properties of the detector. METHODS We calculated G2 and G3 gains resulting from the optimization of the coincidence and energy window width for prompts and singles, respectively. Both quantitative and image-based validated Monte Carlo models of Lu2SiO5 (LSO) TOF-permitting and Bi4Ge3O12 (BGO) TOF-nonpermitting detectors were used for the calculations. RESULTS G2 and G3 values were 1.05 and 1.08 for the BGO detector and G3 was 1.07 for the LSO. A value of almost unity for G2 of the LSO detector indicated a nonsignificant optimization by altering the energy window setting. G' was found to be ∼1.4 times higher for the TOF-permitting detector after reconstruction and optimization of the coincidence and energy windows. CONCLUSION The method described could potentially predict image noise variations by altering detector acquisition parameters. It could also further contribute toward a long-lasting debate related to cost-efficiency issues of TOF scanners versus the non-TOF ones. Some vendors re-engage nowadays to non-TOF product line designs in an effort to reduce crystal costs. Therefore, exploring the limits of image quality gain by altering the parameters of these detectors remains a topical issue.

Over the years, MR systems have evolved from imaging modalities to advanced computational systems producing a variety of numerical parameters that can be used for the noninvasive preoperative assessment of breast pathology. Furthermore, the combination with state-of-the-art image analysis methods provides a plethora of quantifiable imaging features, termed radiomics that increases diagnostic accuracy towards individualized therapy planning. More importantly, radiomics can now be complemented by the emerging deep learning techniques for further process automation and correlation with other clinical data which facilitate the monitoring of treatment response, as well as the prediction of patient’s outcome, by means of unravelling of the complex underlying pathophysiological mechanisms which are reflected in tissue phenotype. The scope of this review is to provide applications and limitations of radiomics towards the development of clinical decision support systems for breast cancer diagnosis and prognosis.

Background Hmox1 plays an important role in the regulation of mitochondrial bioenergetics and function by regulating cellular heme-derived CO and bilirubin. Previous studies have demonstrated that global disruption of HO-1 in humans and mice resulted in severe organ dysfunction. Methods We investigated the potential role of adipose-specific-HO-1 genetic ablation on adipose tissue function, mitochondrial quality control and energy expenditure by generating an adipo-HO-1 knockout mouse model (Adipo-HO-1-/-) and, in vitro, adipocyte cells in which HO activity was inhibited. Adiposity, signaling proteins, fasting glucose and oxygen consumption were determined and compared to adipocyte cultures with depressed levels of both HO-1/HO-2. Results Adipo-HO-1-/- female mice exhibited increased adipocyte size, and decreases in the mitochondrial fusion to fission ratio, PGC1, and SIRT3. Importantly, ablation of HO-1 in adipose tissue resulted in fat acquiring many properties of visceral fat such as decreases in thermogenic genes including pAMPK and PRDM16. Deletion of HO-1 in mouse adipose tissue led to complete metabolic dysfunction, an increase in white adipose tissue, a reduction of beige fat and associated increases in FAS, aP2 and hyperglycemia. Mechanistically, genetic deletion of HO-1 in adipose tissues decreased the mitochondrial fusion to fission ratio; disrupted the activity of the PGC1 transcriptional axis and thermogenic genes both in vitro and in vivo. Conclusion Ablation of adipose tissue-HO-1 abridged PGC1 expression promoted mitochondrial dysfunction and contributed to an increase of pro-inflammatory visceral fat and abrogated beige-cell like phenotype.

Background: Obesity and diabetes are independently associated with the development of cardiac events that occur in db mice that are linked to a decrease in heme oxygenase-1 (HO-1) and epoxyeicosatrienoics (EETs). An increase in HO-1 and EET levels is associated with a decrease of ROS, adiposity and increased mitochondrial function in several animal models. The roles and inter-relationship of HO-1, EET, and PGC-1α in cardiomyopathy pathogenesis has not been investigated. Methods: Obese (db) mice 5 wks of age were allowed to acclimate for 17 wks, and then divided into 3 groups. A) Control, B) EET-A in drinking water, and C) EET-A and lentiviral (Ln) PGC-1α Sh, which decreased PGC1α by 40-60 %. Echocardiography was performed at 5 and 34 wks, serum and heart tissue were harvested to measure signaling and mitochondrial fusion proteins. Results: Group A) developed hyperglycemia, insulin resistance, and LV dysfunction. These changes were associated with decreases in PGC-1α, HO-1, MnSOD, and mitochondrial fusion associated proteins; Mfn 1/2 and OPA-1: Group B), received EET-A, and displayed normal levels of glucose, adipose adiponectin (p Conclusion: An EET-A agonist ameliorates adiposity, BP elevation, mitochondrial function and cardiomyopathy as a result of increased levels of PGC1α and HO-1-expression. Suppression of PGC1α by Ln PGC1α (Sh) worsened insulin resistance suggesting targeting mitochondrial fusion/fission may be a promising therapy for diabetes and heart disease.

Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) expression, and increased mitochondrial function in the 3T3-L1 preadipocyte subjected to adipogenesis. Cells treated with EET resulted in an increase, P

Background/Objectives. Obesity and metabolic syndrome and associated adiposity are a systemic condition characterized by increased mitochondrial dysfunction, inflammation, and inhibition of antioxidant genes, HO-1, and EETs levels. We postulate that EETs attenuate adiposity by stimulating mitochondrial function and induction of HO-1 via activation of PGC-1αin adipose and hepatic tissue.Methods. Cultured murine adipocytes and mice fed a high fat (HF) diet were used to assess the functional relationship among EETs, PGC-1α, HO-1, and mitochondrial signaling using an EET-agonist (EET-A) and PGC-1α-deficient cells and mice using lentiviral PGC-1α(sh).Results. EET-A is a potent inducer of PGC-1α, HO-1, mitochondrial biogenesis (cytochrome oxidase subunits 1 and 4 and SIRT3), fusion proteins (Mfn1/2and OPA1) and fission proteins (DRP1 and FIS1) (p<0.05), fasting glucose, BW, and blood pressure. These beneficial effects were prevented by administration of lenti-PGC-1α(sh). EET-A administration prevented HF diet induced mitochondrial and dysfunction in adipose tissue and restored VO2effects that were abrogated in PGC-1α-deficient mice.Conclusion. EET is identified as an upstream positive regulator of PGC-1αthat leads to increased HO-1, decreased BW and fasting blood glucose and increased insulin receptor phosphorylation, that is, increased insulin sensitivity and mitochondrial integrity, and possible use of EET-agonist for treatment of obesity and metabolic syndrome.

We examined the hypothesis that adipocyte dysfunction in mice fed a high-fat (HF) diet can be prevented by lentiviral-mediated and adipocyte specific-targeting delivery of the human heme oxygenase-1 (aP2-HO-1). A bolus intracardial injection of aP2-HO-1 resulted in expression of human HO-1 for up to 9.5 months. Transduction of aP2-HO-1 increased human HO-1 expression in fat tissues without affecting murine HO-1. In mice fed a HF diet, aP2-HO-1 transduction attenuated the increases in body weight, blood glucose, blood pressure, and inflammatory cytokines, as well as the content of both visceral and subcutaneous fat. Transduction of aP2-HO-1 increased the numbers of adipocytes of small cell size ( P P P P

HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo.Four-month-old HO-2 null (HO-2(-/-)) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2(-/-), and HO-2(-/-) +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days.HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p0.05), (MCP)-1 (p0.05), and (IL-1)-beta (p0.05). These results were accompanied by decreases in HO-1 (p0.05) and subsequently EET and HO activity (p0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p0.05). Cyp2J5 (p0.05), HO-1 (p0.05), and adiponectin mRNA levels (p0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results.Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome.

Purpose Preoperative differentiation between low and high grade gliomas is critical for adapting appropriate treatment strategies. However biopsy based diagnosis presents limitations in assessing tumor diffusive and solid growth patterns, respectively, due to the potential subsampling of tumor region as well as the associated patient risk. The purpose of this study is to investigate the value of imaging biomarker analysis in terms of a 3D texture analysis of T1 pre/post-contrast, T2, and DTI maps in the evaluation of tumor heterogeneity towards glioma grading. Methods In this study a semi-automated segmentation technique, based on T1 pre/post-contrast, T2, and DTI parametric maps, is used for the identification of the tumor core and peritumoral edema regions from 3 Tesla MR Data. 3D Texture analysis was performed on 10 low grade and 10 high grade glioma patients, considering several 3D Histogram, Gray Level Co-Occurrence Matrices (GLCM) and Gray Level Run Length Matrices (GLRLM) derived features. Results Initial evaluation of the proposed method is performed in terms of textural features statistical significant differences between the two tumor groups, with the prospect of implementing an advance classification scheme for identifying more complex correlations. The preliminary results suggest that 3D Texture Analysis findings might be utilized as a surrogate biomarker for the global non-invasive assessment of glioma grading. Conclusions Results demonstrate the potential role of Texture Analysis of 3D tumor imaging appearance in structural MRI, for pre-treatment gliomas grade differentiation.

The Euratom directive 97/43 recommends the use of patient dose surveys in diagnostic radiology and the establishment of diagnostic reference dose levels (DRLs). The aims of this study are to perform measurements of the entrance surface dose (ESD) during diagnostic digital subtraction angiography (DSA) of the renal and carotid arteries using thermoluminescence dosemeters (TLDs), extraction of local DRLs, and calculation of the effective dose. Dose measurement for the staff was also performed. Dose measurements were performed on 48 participating patients. The mean effective dose was calculated to be 15.9 mSv and 8.9 mSv, for the renal and carotid DSA, respectively. The effective dose of the radiologist was calculated to be 0.022 mSv and 0.023 mSv per procedure for renal and carotid DSA respectively, when wearing a protective apron and using a movable ceiling mounted shield. Radiation dose variation depends on the physical characteristics of the patient, on the procedure preferences by radiologists and on the difficulties in conducting the procedures. The lack of DRLs for the specific examinations lead the research team to choose the DRL for DSA of the renal arteries to be 169 mGy for ESD at the pelvic region and for DSA of the carotid arteries to be 313 mGy for ESD at the region of the aortic arc.

Background The Euratom directive 97/43 recommends the use of patient dose surveys in diagnostic radiology and the establishment of reference dose levels (DRLs). Purpose To perform measurements of the dose delivered during diagnostic angiography of the lower limbs using thermoluminescence dosimeters (TLDs), extraction of DRLs and estimation of the effective dose and radiation risk for this particular examination. Methods Dose measurement was performed on 30 patients by using TLD sachets attached in 5 different positions not only on the patient, but also to the radiologist. All the appropriate factors were recorded. Measurement of the ESD was performed after each examination. Results The mean entrance skin dose (ESD) was calculated to be 70.8, 67.7, 24.3, 18.4, 9.7 mGy at the level of aorta bifurcation, pelvis, femur, knees, and at feet, respectively. The average effective dose is 9.8 mSv with the radiation risks for fatal cancer to be 5.4 × 10−4. The effective dose of the radiologist was calculated to be 0.023 mSv per procedure. Conclusion Radiation dose variation depends on the physical characteristics of the patient, on the procedure preferences by radiologists and the difficulties in conducting procedures. The main reason for the increased patient dose, compared to other studies, is the number of frames rather than the duration of fluoroscopy. For DSA of the lower limbs, the DRL was chosen to be an entrance skin dose of 96.4 mGy in the pelvic region. The dose to the radiologist is negligible.

The aims of the present study were to assess whether sustained HO-1 expression could moderate or prevent diabetes in an animal model of the disease and, if so, to examine the possible mechanisms involved. Our results showed that HO-1 expression and HO activity were upregulated in the pancreas of non-obese diabetic (NOD) mice by the weekly administration of cobalt protoporphyrin (CoPP). Blood glucose levels in CoPPtreated mice decreased to normal, but continuously increased in untreated controls. Beta-cell numbers were preserved in the islets of CoPP-treated mice, whereas no beta cells were found in untreated diabetic mice. The number of CD11c(+) dendritic cells was significantly decreased in the pancreas of CoPP-treated NOD mice, but this effect was reversed by the inhibition of HO activity. Increased levels of HO-1 produced a new pancreatic phenotype, as reflected by increases in phosphorylated AKT, BcL-xL and RSK levels, and decreases in O(2)- and 3-NT levels. These novel findings provide a link between the increase in HO-1 activity, with its concurrent enhanced production of carbon monoxide (CO) and bilirubin, a decrease in infiltrated CD11c(+) dendritic cells and an increase in anti-apoptotic proteins, including RSK and BcL-xL, in the interdiction of the diabetic state.

Heme oxygenase-1 (HO-1) is crucial in regulating oxidative injury. The present study was designed to assess whether HO-1 upregulation by cobalt protoporphyrin IX (CoPP) moderates or prevents the diabetic state in non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes (T1D). HO-1 expression and HO activity were upregulated in the pancreas by the intermittent administration of CoPP. This was associated with decreases in blood glucose and pancreatic O2-, but increased pAKT and BcL-XL and cell survival. A considerable number of beta cells were preserved in the islets of CoPP-treated NOD mice, while none were found in untreated diabetic mice. The number of CD11c+ dendritic cells was decreased in the pancreas of CoPP-treated NOD mice (p < 0.05). These novel findings provide a link between the increase in HO-1 and a decrease in infiltrated CD11c+ dendritic cells, and suggest that induction of HO-1 activity can be used to enhance cell survival and moderate the diabetic state in T1D.

The objective of this study was to assess the efficacy of bovine pericardium (BP) as a patch material in carotid endarterectomy (CEA) in terms of peri- and postoperative complications and the incidence of recurrent stenosis. During a 4-year period, 148 CEAs were performed in 138 consecutive patients. The study group included elective, emergency, and combined with cardiac operation CEAs in both symptomatic and asymptomatic carotid artery disease patients. Patch angioplasty using the BP followed the standard CEA in all patients. Postoperative follow-up included clinical examination and periodical color duplex scans at 3, 6, and 12 months and yearly thereafter. Surgical outcome was evaluated by the operation-related parameters, early and late mortality and morbidity rates, and the incidence of recurrent stenosis. All CEAs were performed without any unfavorable event. In the early postoperative period, there were no deaths and the morbidity consisted of transient cranial nerve paresis (4.7%) in seven patients and two ipsilateral strokes (1.4%). During the follow-up period, three patients (2%) developed significant carotid restenosis, though they remain asymptomatic, while there were no deaths related to the CEA. Patch angioplasty of the carotid artery using BP showed unwittingly early and mid-term surgical outcome. Our results demonstrate the BP to be a suitable patch material for routine use in carotid surgery.

Background Various laparoscopic techniques have been described for the insertion of peritoneal dialysis catheters. However, most use 3 to 4 ports, thus multiplying the potential risk for abdominal wall complications (hemorrhage, hernia, leaking). Methods A Tenckhoff catheter was placed laparoscopically, using just 1 port, in 13 consecutive patients with end-stage renal failure. All catheters were fixed in the abdominal cavity with no additional ports for this purpose. Results After a follow-up of 76 patient-months, all catheters are working properly. There were no postoperative wall hemorrhages, early leaking, or hernias. There was 1 case of catheter migration and 2 cases of late leaking in 2 patients in total, due to severe constipation. There were no exit site or tunnel infections. One episode of peritonitis was successfully treated with antibiotics. Conclusion The simplicity and the rapidity of the method justifies serious consideration for its use as the standard Tenckhoff catheter placement.

Reduction/loss of E-cadherin is associated with the development and progression of many epithelial tumors, while in a limited number of neoplasms, E-cadherin is re-expressed in metastases. Dysadherin, recently characterized by members of our research team, has an anti-cell-cell adhesion function and downregulates E-cadherin in a posttranscriptional manner. Colorectal cancer (CRC) is one of the most common tumors in the developed world, and lymph node metastases are harbingers of aggressive behavior. The aim of the present study was to examine the dysadherin and E-cadherin expression patterns in lymph node metastases vs primary CRC. Dysadherin and E-cadherin expression was examined immunohistochemically in 78 patients with CRC, Dukes' stage C in the primary tumor and in one lymph node metastasis. Dysadherin was expressed in 42% while E-cadherin immunoreactivity was reduced in 45% of primary tumors. In lymph nodes, 33 and 81% of metastatic tumors were positive for dysadherin and E-cadherin, respectively. Dysadherin expression was not correlated with E-cadherin expression in the primary tumor with a reverse correlation evident in the lymph node metastases. Our results suggest that different mechanisms govern E-cadherin expression in the primary tumor and the corresponding lymph node metastases.

The choice of the appropriate model and parameter set in determining the relation between the incidence of radiation pneumonitis and dose distribution in the lung is of great importance, especially in the case of breast radiotherapy where the observed incidence is fairly low. From our previous study based on 150 breast cancer patients, where the fits of dose-volume models to clinical data were estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the relative seriality is significantly better than the LKB NTCP model. However, the estimation of the different NTCP models was based on their goodness-of-fit on clinical data, using various sets of published parameters from other groups, and this fact may provisionally justify the results. Hence, we sought to investigate further the LKB model, by applying different published parameter sets for the very same group of patients, in order to be able to compare the results. It was shown that, depending on the parameter set applied, the LKB model is able to predict the incidence of radiation pneumonitis with acceptable accuracy, especially when implemented on a sub-group of patients (120) receiving [see text]|EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain radiobiological model on a given clinical case is closely related to the selection of the proper scoring criteria and parameter set as well as to the compatibility of the clinical case from which the data were derived.

Previous studies showed equivocal findings regarding the efficacy of focused attention and distraction to experimental pain. This study examined the relative efficacy of these strategies on perception of cold pressor pain in 41 chronic back pain patients and 41 healthy control participants. Participants were randomized to the 2 strategies and then completed a 7-minute cold pressor test. Pain intensity and discomfort ratings were obtained during the task. Participants who completed the first task were asked to complete a second cold pressor task without instructions. Pain and discomfort ratings differed by condition across time. In the distraction condition, pain levels started low but continued to rise throughout the cold pressor immersion, whereas in the focused attention condition, pain levels started higher, rose less quickly, and then decreased from the middle of the task. Focused attention was associated with higher pain and lower completion rates in chronic pain patients compared with healthy control subjects. Focused attention might therefore not be an effective intervention strategy for individuals with chronic back pain. Finally, in the second cold pressor test, patients’ pain reports rose more rapidly than those of healthy control subjects. The results of this study can be explained in terms of differences in cognitive appraisal between pain patients and healthy control participants. Perspective Marked differences were found between chronic back pain patients and control participants regarding focused attention as compared with distraction as a means of coping with cold pressor–induced pain. These differences underline the importance of taking into account previous experience with pain when recommending strategies to cope with painful procedures.

A parthenogenetic Artemia population from Torre Colimena, southern Italy, originally reported in 1998, is characterized by a multidisciplinary approach including cyst and naupliar biometry, morphometry of adults, scanning electron microscopy (SEM) of brood pouch, cytogenetics and 16S rRNA PCR-RFLP analysis. We confirmed parthenogenetic status, inferred ploidy level and determined phenotypic and molecular relationships of this population through comparisons with other asexual Artemia strains as well as bisexual species found (A. salina) or introduced (A. franciscana) in the Mediterranean basin. Cyst and naupliar sizes for Torre Colimena are among the smallest recorded for asexual Artemia while the opposite is true for chorion thickness. Discriminant analysis of adult body measurements shows increased differentiation (89.5% for the first four out of the taselve functions produced) from tetraploid parthenogenetic strains and bisexual species (A. salina and A. franciscana). Scanning electron micrographs of brood pouch reveal the characteristic morphology of asexual strains, while chromosome observations of instar-I nauplii unequivocally establish diploid>. Restriction patterns give evidence that the Torre Colimena population shares an identical set of mitochondrial DNA (mtDNA) polymorphisms with a diploid Spanish parthenogenetic strain and it is well differentiated from other tetraploid as well as bisexual auto- and allochthonous strains (A. salina and A. franciscana) from the Mediterranean. The present study may serve as a reference methodological framework for multidisciplinary characterization and biodizjersiy assessments in the genus Artemia.

Patients with diabetes mellitus are well known to be at high risk for vascular disease. Circulating endothelial cells (CECs) have been reported to be an ex vivo indicator of vascular injury. We investigated the presence of CECs in the peripheral blood of 25 patients with diabetes mellitus and in nine non-diabetic control donors.Endothelial cells were isolated from peripheral blood with anti-CD-146-coated immunomagnetic Dynabeads, and were stained with acridine orange dye and counted by fluorescence microscopy. The cells were also stained for von Willebrand factor and Ulex europaeus lectin 1.Patients with diabetes mellitus had an elevated number of CECs (mean 69+/-30 cells/ml, range 35-126) compared with healthy controls (mean 10+/-5 cells/ml, range 3-18) (p0.001). The increase in CECs did not correlate with the levels of HbA(1)c. Circulating endothelial cell numbers were elevated regardless of glucose levels, suggesting that, even with control of glucose levels, there is increased endothelial cell sloughing.Our study suggests that the higher number of CECs in patients with type 2 diabetes may reflect ongoing vascular injury that is not directly dependent on glucose control.

BACKGROUND: Preoperative staging of rectal cancer is essential for the selection of the optimal treatment. This study aims to evaluate the accuracy of endorectal ultrasonography (EUS) in local staging of rectal cancer. PATIENTS AND METHODS: During a 4-year period, 33 patients with biopsy-proven rectal cancer underwent evaluation of the invasion of the rectal wall, the mesorectal lymph nodes status and the pelvic organs using EUS. We compared the EUS findings (uTN) to the histopathology examination of the resected specimens (pTN) according to TNM classification. RESULTS: Most patients had T3 tumours. Overall accuracy in assessing the depth of rectal wall invasion (T) and the lymph node status was 79% and 59% respectively. Two patients previously treated by preoperative chemoradiation were correctly staged only for N stage. CONCLUSIONS: EUS is a valuable diagnostic tool in local staging of rectal cancer. Progressively increasing experience will overcome the obstacles in accurate interpretation of ultrasound images. Tech Coloproctol

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Flatness and symmetry are main parameters determining the quality of a photon beam produced by linear accelerators. The quality assurance in routine clinical practice of radiotherapy and consequently the treatment-outcome depend definitely on the physical parameters of treatment-delivery. Several recommendations from national and international associations are reported. By reviewing the current literature and mainly according to the World Health Organization (WHO) report of quality assurance in radiotherapy, we may suggest that for flatness and symmetry, the optimal level of deviation should be within ± 3%. Flatness and symmetry should be checked monthly or once a year in accordance to the guidelines of national societies.

To identify the prognostic variables and to assess the role of aggressive management in patients with Fournier's gangrene.Retrospective study.University hospital, Greece.11 patients (9 men and 2 women) with Fournier's gangrene admitted between April 1986 and December 2000.Early aggressive debridements.Postoperative course, hospital stay, outcome, morbidity, and mortality.The mean age was 65 years (range 17-90) and the mean (SD) duration of hospital stay was 35 (8) days (range 8-62). The aetiology was identified in 8 patients and idiopathic in 3. Predisposing factors (diabetes, n = 4; heart failure, agranulocytosis, and alcohol misuse, n = 1 each) were identified in 6 patients. All patients except one had raised serum glucose concentrations and low serum albumin values. On admission the white cell count was15 x 10(9)/L in 10, serum sodium135 mmol/L, mean (SD) serum creatinine 124 (27) micromol/L, and C-reactive protein150 mg/L was found in all patients. 3/9 male patients required partial excision of the scrotum. Temporary faecal diversion was done for 3 patients. A mean of 3 aggressive repeated debridements (range: 3-6) were required. Nine patients survived and two patients died.Rapid and accurate diagnosis remains the key to achieving a successful outcome. Abnormal laboratory variables on admission may suggest the diagnosis. Early, repeated, aggressive debridement is essential for a successful outcome.

The role of conventional Magnetic Resonance Imaging (MRI) in the detection of cerebral tumors has been well established. However its excellent soft tissue visualization and variety of imaging sequences are in many cases non-specific for the assessment of brain tumor grading. Hence, advanced MRI techniques, like Diffusion-Weighted Imaging (DWI), Diffusion Tensor Imaging (DTI) and Dynamic-Susceptibility Contrast Imaging (DSCI), which are based on different contrast principles, have been used in the clinical routine to improve diagnostic accuracy. The variety of quantitative information derived from these techniques provides significant structural and functional information in a cellular level, highlighting aspects of the underlying brain pathophysiology. The present work, reviews physical principles and recent results obtained using DWI/DTI and DSCI, in tumor characterization and grading of the most common cerebral neoplasms, and discusses how the available MR quantitative data can be utilized through advanced methods of analysis, in order to optimize clinical decision making.

Objective. The religious convictions of parents who are Jehovah’s Witness adherents lead them to reject the use of exchange transfusions as therapy for severe hyperbilirubinemia in newborns in whom intensive phototherapy has failed to control this problem. Consequently, physicians caring for such infants may be obliged to initiate legal action to compel use of the procedure when severe hyperbilirubinemia not sufficiently responsive to phototherapy warrants an exchange transfusion. Our goal was to determine if we could use the potent inhibitor of bilirubin production, Sn-Mesoporphyrin (SnMP), to resolve the troubling medical-legal issues in such situations in 2 infants with hemolytic disease of the newborn who required exchange transfusions for severe hyperbilirubinemia but whose Jehovah’s Witness parents rejected the procedure. SnMP was administered in a single dose, as in previous studies, at the time when exchange transfusion would have been initiated and plasma bilirubin levels were monitored at close intervals thereafter.Methods. SnMP is a potent inhibitor of heme oxygenase, the rate-limiting enzyme in catabolism of heme to bilirubin. We found in earlier studies that in single doses of 6 μmol/kg birth weight, SnMP is extremely effective in moderating the course of hyperbilirubinemia and in eliminating the need for supplemental phototherapy in jaundiced newborns. In the 2 cases described, a single dose of SnMP (6 μmol/kg birth weight) was administered intramuscularly to severely jaundiced infants with immune hemolysis at a time when clinical circumstances dictated the need for exchange transfusion.Case 1. This patient was a preterm male infant (gestational age: 35 5/7 weeks; birth weight: 2790 g) whose plasma bilirubin concentration (PBC) at 1 hour after birth was 5.0 mg/dL. Despite intensive phototherapy with 3 banks of lights and 1 biliblanket, the PBC increased steadily with no diminution in the rate of increase for 75 hours. In view of the problems of immune hemolysis, and prematurity, and the inability of phototherapy to stop progression of hyperbilirubinemia, a decision to carry out an exchange transfusion was made; the decision was, however, rejected by the Jehovah’s Witness parents. Pending legal action to compel use of the procedure, a request to this (Rockefeller) laboratory for SnMP was made; its use was approved by the Food and Drug Administration; and the inhibitor was delivered to the physician-in-charge (D.P.M.) in Sioux Falls, South Dakota. The single dose of SnMP was administered to the infant at 75 hours after birth; the course of hyperbilirubinemia before and after the use of the inhibitor is shown in Fig 1.Case 2. This female term infant (gestational age: 38–39 weeks; birth weight: 4140 g) with immune hemolysis was delivered by cesarean section and because of problems related to meconium aspiration required helicopter transfer to the Special Care Nursery in Abilene, Texas, where 10 hours after birth the first PBC was determined to be 18.0 mg/dL. Double-bank phototherapy plus a biliblanket was initiated; a third bank of lights was later ordered. The PBC fluctuated in the ensuing 2 days between 13.8 to 25.8 mg/dL during which suggestive clinical signs of possible bilirubin encephalopathy became manifest. In view of the clinical circumstances and the continued severe hyperbilirubinemia, permission for a double-exchange transfusion was requested. The parents, who were Jehovah’s Witness adherents, refused the procedure. While preparing legal action to compel use of the exchange, a request was made to this (Rockefeller) laboratory for use of SnMP to attempt control of hyperbilirubinemia. With FDA approval, the SnMP was delivered to the attending neonatologist (J. R. M.) in Abilene and administered in a single dose (6 μmol/kg birth weight) at 56 hours after birth when the PBC was 19.5 mg/dL. The course of bilirubinemia before and after SnMP use is shown in Fig 2.Results and Conclusions. The use of SnMP to moderate or prevent the development of severe hyperbilirubinemia in newborns (preterm, near-term, term with high PBCs [15–18 mg/dL], ABO-incompatibility; glucose-6-phosphate dehydrogenase deficiency) has been extensively studied in carefully conducted clinical trials the results of which have been reported earlier. This inhibitor of bilirubin production has demonstrated marked efficacy in moderating the course of hyperbilirubinemia in all diagnostic groups of unconjugated neonatal jaundice. The 2 cases described in this report confirmed the efficacy of SnMP in terminating progression of hyperbilirubinemia in infants in whom phototherapy had failed to sufficiently control the problem and whose parents, for religious reasons, would not permit exchange transfusions. Interdiction of severe hyperbilirubinemia by inhibiting the production of bilirubin with SnMP can be an effective alternative to the use of exchange transfusion in the management of severe newborn jaundice that has not responded sufficiently to light treatment to ease concern about the development of bilirubin encephalopathy.

OBJECTIVE: This study was undertaken to assess the quality of life of patients after surgical treatment of anal fistula and to investigate whether anal manometry (AM) can guide the choice of the proper surgical intervention in these patients in order to protect the sphincter mechanism. PATIENTS AND METHODS: One hundred patients with anal fistula (AF) were studied prospectively (78 men; mean age 45 years; range 11-78). Cleveland Incontinence Score (CIS) was record pre-operatively and 1 and 3 months postoperatively for each patient in order to specify their quality of life (QOL) before and after the surgical treatment. Also, anal manometry (AM) was performed pre-operatively and 1 month postoperatively. The pre-operative anal pressures and the type of fistula determined the kind of the surgical treatment. 55 patients had an intersphincteric fistula, 42 trans-sphincteric and 3 suprasphincteric. 65 patients underwent laying open of the fistulous track, 7 fistulectomy and 28 were treated by seton fistulotomy. RESULTS: Three patients had defective gas control and 6 reported some degree of soiling. 3 patients developed recurrent fistula. CIS was significantly impaired (P=0.02) at the first postoperative month in these patients who were treated for trans-sphincteric fistula by fistulotomy; AM revealed significant decrease of anal pressures in these patients (resting and squeeze; P=0.007 and 0.0001 respectively); CIS and AM in the remaining cases revealed no significant deterioration of QOL and fall of anal pressures respectively. CIS was normal in the vast majority of patients at 3-months postoperatively. CONCLUSIONS: QOL of patients after surgical treatment of AF is unalterable on the understanding that the AF is simple and the treatment is not associated by incontinence or recurrence. Pre-operative AM is important regarding the choice of the proper surgical procedure. Colorectal Dis

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5×10 9 to 1×10 10 colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

Although swallowing difficulties have been described in patients with Kearns-Sayre syndrome (KSS), the spectrum of manometric characteristics of dysphagia is not yet well known. Moreover, it is conceivable that a combination of various degrees of swallowing difficulties with different patterns in manometric studies exist, each playing a major role in the prognosis, natural history, and quality of life of KSS patients. An 18-year-old girl diagnosed at the age of 5 years with KSS (muscle biopsy) was admitted to our department with an upper respiratory tract infection and dysphagia. Clinical examination revealed growth retardation, external ophthalmoplegia, pigmentary retinopathy, impaired hearing, and ataxia. An electrocardiogram revealed cardiac conduction defects (long Q-T), and brain magnetic resonance imaging showed abnormalities in the cerebellar hemispheres. A manometric and motility study for dysphagia was conducted and the pharynx and upper esophageal sphincter (UES) resting pressures were similar to control group values, but the swallowing peak contraction pressure of the pharynx and the closing pressure of the UES were very low and could not promote effective peristaltic waves. Relaxation and coordination of the UES were not affected although pharyngeal and upper esophagus peristaltic waves proved to be very low and, consequently, were practically ineffective. The patient was started on treatment comprising a diet rich in potassium, magnesium, and calcium, and oral administration of vitamin D and co-enzyme Q10 100 mg daily; she was discharged 6 days later with apparent clinical improvement. Dis Esophagus

UICC classification accurately predicts overall survival but not recurrence-risk. We report here data of overall and first site-specific recurrence following curative surgery useful for the development of recurrence-oriented preventive target therapies. Patients who underwent resection for gastric cancer were stratified according to curability of surgery [curative (R0) vs non-curative resection], extent of surgery [limited (D1) vs extended (D2) node dissection] and pathological nodal/serosal status. The intent-to-treat principle, log-rank test and Cox regression analysis were used for statistical analysis of time-to-event (recurrence, death) endpoints. Curative resection only produced a chance of cure whereas survival was very poor following non-curative resection (P

The objective of the dynamic radiotherapy project 'Dynarad' within the European Community has been to compare and grade treatment techniques that are currently applied or being developed at the participating institutions. Cervical cancer was selected as the tumour site on the grounds that the involved organs at risk, mainly the rectum and the bladder, are very close to the tumour and partly located inside the internal target volume. In this work, a solid phantom simulating the pelvic anatomy was used by institutions in Belgium, France, Greece, Holland, Italy, Sweden and the United Kingdom. The results were evaluated using both biological and physical criteria. The main purpose of this parallel evaluation is to test the value of biological and physical evaluations in comparing treatment techniques. It is demonstrated that the biological objective functions allow a much higher conformality and a more clinically relevant scoring of the outcome. Often external beam treatment techniques have to be combined with intracavitary therapy to give clinically acceptable results. However, recent developments can reduce or even eliminate this need by delivering more conformal dose distributions using intensity modulated external dose delivery. In these cases the reliability of the patient set-up procedure becomes critical for the effectiveness of the treatment.

Several growth factors, such as growth hormone and insulin-like growth factor-1, have been used to reverse the high rate of catabolism observed either after an operation or during serious illness. We conducted a pilot study in Wistar rats in an attempt to assess whether regulatory peptides widely used in clinical practice, such as erythropoietin (EPO) and granulocyte macrophage colony-stimulating factor (GM-CSF), alone or in combination, might influence the metabolism after surgery. Forty animals were randomly allocated into four groups (one control group and three experimental groups; 10 animals per group). The rats in the control group received isotonic NaCl; the rats in one experimental group received recombinant human EPO (rHuEPO) at a dose of 500 IU/kg (EPO group) and those in another received recombinant GM-CSF at a dose of 20 microg/kg (GM-CSF group); in the fourth group, each animal received the two drugs in combination (EPO/GM-CSF group). In all groups, rats were given the drug(s) or NaCl daily for 15 days before the operation and for 7 days after the operation until they were killed. We estimated the body weight (g) and the hematocrit (%) on the first day of the experiment (baseline values) and on the seventh day after the operation, and we estimated the rate of healing and the breaking strength of the intestinal anastomosis on the day the rats were killed. At the end of the study we found that the body weight (median 250 g, minimum 230 g, maximum 270 g) and the levels of hematocrit (median 64%, minimum 60%, maximum 65%) were significantly increased in the EPO group (P < .001 and P < .005, respectively) as compared with the baseline values (median 217.5 g, minimum 200 g, maximum 250 g; median 51.5%, minimum 45%, maximum 55%, respectively). A similar significant increase in body weight (median 230 g; minimum 200 g; maximum 250 g) and hematocrit (median 64%; minimum 59%; maximum 67%) was found at the end of the study in the EPO/GM-CSF group (P = .01 and P < .005, respectively) as compared with the baseline values (median 210 g; minimum 200 g; maximum 250 g; median 50%, minimum 48%, maximum 54%, respectively). The breaking strength (in newtons (N)) statistically differed in the four groups (Kruskal-Wallis, P = .0008). A comparison between groups showed that the breaking strength had been significantly increased in the animals in the EPO group (median 2.18 N, minimum 1.98 N, maximum 2.44 N) as compared with those in the control group (median 1.66 N, minimum 1.33 N, maximum 1.87 N; P = .004), GM-CSF group (median 1.73 N, minimum 1.25 N, maximum 2.07 N; P < .005), and EPO/GM-CSF group (median 1.71 N, minimum 1.37 N, maximum 1.91 N; P = .0005). In conclusion, this study demonstrated that the administration of rHuEPO appears to have a beneficial positive effect on the body weight, hematocrit, and healing rate and the breaking strength of large bowel anastomoses in rats. These observations provide evidence of an as-yet-unknown anabolic effect of EPO, and they may expand its usual applications. However, more studies are needed to confirm our findings and furthermore to define the optimal dose and timing of EPO administration. J Lab Clin Med

We report a rare case of a cellular neurilemoma (schwannoma) of the descending colon, mimicking carcinoma, not accompanied by von Recklinghausen's disease. The differential diagnostic problems are discussed and the possibility of a site-specific, modified Schwann cell of myenteric plexus origin is suggested.

Type-1 cardiorenal syndrome, characterized by acute kidney dysfunction secondary to cardiac failure and renal arteriolar vasoconstriction, is mediated by the renin–angiotensin–aldosterone axis and sympathetic nervous system activation. Previous reports indicate that angiotensin II modulates immune function and causes recruitment and activation of T-lymphocytes. The goal of this study was to evaluate the effects of postischemic heart failure on renal morphology and circulation and the beneficial effects of heme oxygenase-1 (HO-1) induction in T-lymphocyte–suppressed severe combined immune deficiency (SCID) mice. Mice were divided into 4 groups: sham, myocardial infarction (MI), MI treated with an HO-1 inducer, cobalt protoporphyrin, and with or without stannous mesoporphyrin, an inhibitor of HO activity. Heart and kidney function were studied 30 days after surgery. Fractional area change was reduced 30 days after surgery in both the C57 and SCID MI–groups as compared with their respective controls ( P P

The aim of this study was to assess the role of known risk factors and specifically evaluate the role of pancreatitis potentially associated drugs as potential risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).This was a prospective, single-center cohort study conducted in a tertiary university hospital. All eligible ERCP procedures within a 16-month period were evaluated, and all interventions, patient characteristics, and medications used were documented. The association of potential risk factor with PEP was investigated with univariable analyses. Those statistically significant were entered in a multivariable regression model.Three hundred eighteen ERCP procedures were studied. Post-ERCP pancreatitis occurred in 28 patients (8.8%). Twenty-three potential risk factors were studied in univariable analyses, and 3 of them were found to be nominally statistically significant. These 3 factors were independently associated with PEP in the multivariable model and included the use of pancreatitis potentially associated drugs, belonging to Badalov classes I or II, during the last month before ERCP (odds ratio [OR], 4.39; 95% confidence interval [CI], 1.70-5.47; P = 0.003), more than 1 guide-wire insertions in the pancreatic duct (OR, 5.00; 95% CI, 1.97-12.81; P = 0.001) and bile duct stone extraction (OR, 0.12; CI, 0.05-0.32; P0.001).Pancreatitis potentially associated drugs used before ERCP seem to increase the risk for PEP.

Despite a marked decline in its incidence, gastric cancer remains the second most common cause of cancer-related deaths worldwide. More radical surgical procedures have been introduced and assessed as most patients die from locoregional tumour recurrence after intended curative resection. Many, mainly Japanese and some Western surgeons, believe that the leading cause of local treatment failure is the insufficient nodal clearance. On the other hand, many surgeons in the West regard the lymph nodes as indicators rather than determinants of the disease. According to this view, extensive resection mainly improves the accuracy of the tumour staging and not survival. As a consequence, the extent of lymph-node dissection is a highly controversial issue. Lymphatic spread has long been recognized as a major prognostic factor in gastric cancer. However, the different staging systems that are practised in Japan and the West confuse the comparison of survival results. According to the Japanese Research Society for the Study of Gastric Cancer (JRSGC) (I), the upper abdominal lymph nodes are numbered from 1 to 16 and subsequently grouped into four levels, designated Nl-N4. The grouping into levels depends on the location of the primary tumour, and relates to increasing anatomical distance from the stomach. Dissection of the first level (Nl) of lymph nodes, those directly attached to the stomach, is referred to as Dl dissection; in extended lymph-node disseciton (D2), the second-level (N2), those surrounding the vessels of the celiac axis and in the splenic hilum, are removed. Even wider dissections (D3 or D4) are practised in Japan, but only for patients with suspected invasion of these lymph-nodes levels (N3 or N4). In the Western countries, the tumour nodes metastases (TNM) staging system of the International Union Against Cancer (UICC) is used for the classification of lymph-node involvement (2). Pathologically-assessed involved lymph nodes are classified in pN-categories: pN0, nodes without metastases; pN1, metastases