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Frozen section analysis ( FS) during cancer surgery is widely used to assess resection margins. However, in hilar cholangiocarcinoma ( HCCA), FS may be less reliable because of the specific growth characteristics of the tumor. The aim of this study was to determine the accuracy and consequences of intraoperative FS of the proximal bile duct margins in HCCA. Between 1990 and 2014, 67 patients underwent combined extrahepatic bile duct resection and partial liver resection for HCCA with the use of FS. Sensitivity and specificity of FS was 68% and 97%, respectively. Seventeen of 67 patients (25%) displayed a positive bile duct margin at FS. The false-negative rate was 16% (eight patients). Ten patients (15%) with a positive bile duct margin underwent an additional resection in an attempt to achieve negative margins, which succeeded in three patients (4%). However, only one of these three patients did not have concomitant lymph node metastases, which are associated with a poor prognosis by itself. The use of FS of the proximal bile duct is of limited clinical value because of the relatively low sensitivity, high risk of false-negative results, and the low rate of secondary obtained tumor-free resection margins. Supported by the literature, a new approach to the use of FS in HCCA should be adopted, reserving the technique only for cases in which a substantial additional resection is possible. [ABSTRACT FROM AUTHOR]

Background: Choledochal malformation (CM) is a rare medical condition of which 80% are diagnosed in pediatric patients. There are several important controversies regarding diagnostic workup, management, and follow-up in these pediatric patients. To assess preferences and practices of Dutch pediatric surgeons regarding the diagnostic procedures, management, and follow-up of children with CM we conducted an electronic survey.Methods: A questionnaire was sent to all the pediatric surgeons working in the academic centers and the only community hospital with a pediatric surgery service. The questionnaire included, items regarding incidence, diagnostic workup, interval between diagnosis and surgery, surgical techniques, and follow-up. We also assessed whether personal exposure influenced the preferences and practices.Results: Overall 22 out of the 31 (71%) Dutch pediatric surgeons returned the questionnaire. Total 15 out of 22 (68%) encountered CM up to 2 times/y, whereas 7 out of 22 (32%) encountered it more than 2 times/y. Indications for surgery were significantly different between surgeons who encountered CM > 2 time/y versus those who did not: 6/6 (100%) of surgeons encountering CM > 2 times/y considered the presence of an asymptomatic CM an indication for surgery versus 5/14 (36%) of the pediatric surgeons who encountered a CM up to 2 times/y (p = 0.01). Overall 12 out of the 22 (55%) respondents preferred surgery between 6 months and 2 years of age. The amount of exposure did not differ in preferred age at surgery or surgical technique. In the symptomatic child 10/22 (45%) of respondents preferred surgery within 3 months. Overall 7/22 (32%) favored laparoscopic resection. Hepaticojejunostomy with Roux-en-Y reconstruction was the preferred reconstruction for all the respondents. One-third stated that they never performed a parenchyma resection. Follow-up was limited to 10 years in almost half of the respondents.Conclusion: Dutch pediatric surgeons demonstrate a wide variety of opinions regarding diagnostic workup, treatment, and follow-up of CM. While most surgeons encounter CM up to 2 times/y, there is an association between exposure and several of the outcome parameters. Some of the answers are not in line with the expert opinion. This demonstrates that there is a need for evidence-based (inter)national guidelines regarding the diagnostic approach, management, and follow-up. [ABSTRACT FROM AUTHOR]

Little is known about the achievement of developmental milestones (i.e., COL) after pediatric liver transplantation. The aim of this study was to examine the COL of young adults who underwent a liver transplantation during childhood and to compare it to healthy peers. Furthermore, we studied factors possibly related to their COL. COL was assessed using the CLQ, which assesses the achievement of developmental milestones (autonomy, psychosexual, social, and antisocial development) and risk behavior (substance abuse and gambling). Sociodemographic characteristics and clinical data were collected using the prospective institutional liver transplantation database. A total of 39 young adults who underwent a liver transplantation at the UMCG in their childhood completed the CLQ. They achieved fewer milestones with regard to autonomy, psychosexual, and social development compared to healthy peers, and they reported less risk behavior. Neither age at the time of study nor age at the time of transplantation was significantly correlated with any of the COL subscales. Young adults show delay in reaching developmental milestones in every dimension after a liver transplantation during their childhood. [ABSTRACT FROM AUTHOR]

Introduction Gaining an insight into the quality of life (QOL) in long-term biliary atresia (BA) survivors is becoming more important. Identifying patients with limitations might make tailor made interventions possible. This is the first study investigating the health status (HS) and QOL in adults surviving BA with their native livers, and comparing them with healthy peers. Methods BA patients surviving with their native liver were identified in the Netherlands Study Group on Biliary Atresia Registry database. The RAND-36 and the World Health Organization Quality of Life assessment instrument-100 (WHOQOL-100) were used to measure HS and QOL, respectively. Correlation between the RAND-36 and WHOQOL-100 was also assessed. Hospital Anxiety and Depression Scale (HADS) and the Impact Event Scale (IES) were also completed. Results In total, 25 (83%) of the 30 eligible patients after Kasai portoenterostomy completed the questionnaires (median age 23.2 years). A lower perceived level of general health in HS was found as compared with the reference group and a higher score on the social domain was reported in QOL. Correlations between HS and QOL questionnaires were moderate to good. For the group, overall HADS and IES scores were good, though individual patients did score above the cutoff of both the questionnaires. Conclusion Adult BA patients surviving with their native liver have similar HS and QOL as compared with their healthy peers. RAND-36 and WHOQOL-100 questionnaires are not interchangeable, but complementary to assess the patients' outcomes. The overall scores did not point to increased levels of anxiety and depression. However, on an individual level, three and six patients had a score above the cutoff of the HADS subscales demonstrating clinically relevant levels of anxiety and depression, respectively. [ABSTRACT FROM AUTHOR]

The article presents a case study about a 25-year-old man with a progressively enlarge and swell right side of the neck in which clinical differential diagnoses of nocardiosis, cervicothoracic actinomycosis and lymphoma.

Background Effective chemotherapy rapidly reduces the spin--lattice relaxation of water protons (T1) in solid tumours and this change (ΔT1) often precedes and strongly correlates with the eventual change in tumour volume (TVol). To understand the biological nature of ΔT1, we have performed studies in vivo and ex vivo with the allosteric mTOR inhibitor, everolimus. Mice bearing RIF-1 tumours were studied by magnetic resonance imaging (MRI) to determine TVol and T1, and MR spectroscopy (MRS) to determine levels of the proliferation marker choline and levels of lipid apoptosis markers, prior to and 5 days (endpoint) after daily treatment with vehicle or everolimus (10 mg/kg). At the endpoint, tumours were ablated and an entire section analysed for cellular and necrotic quantification and staining for the proliferation antigen Ki67 and cleaved-caspase-3 as a measure of apoptosis. The number of blood-vessels (BV) was evaluated by CD31 staining. Mice bearing B16/BL6 melanoma tumours were studied by MRI to determine T1 under similar everolimus treatment. At the endpoint, cell bioluminescence of the tumours was measured ex vivo. Results Everolimus blocked RIF-1 tumour growth and significantly reduced tumour T1 and total choline (Cho) levels, and increased polyunsaturated fatty-acids which are markers of apoptosis. Immunohistochemistry showed that everolimus reduced the%Ki67+ cells but did not affect caspase-3 apoptosis, necrosis, BV-number or cell density. The change in T1 (ΔT1) correlated strongly with the changes in TVol and Cho and%Ki67+. In B16/BL6 tumours, everolimus also decreased T 1 and this correlated with cell bioluminescence; another marker of cell viability. Receiver-operating-characteristic curves (ROC) for everolimus on RIF-1 tumours showed that ΔT1 had very high levels of sensitivity and specificity (ROCAUC = 0.84) and this was confirmed for the cytotoxic patupilone in the same tumour model (ROCAUC = 0.97). Conclusion These studies suggest that ΔT1 is not a measure of cell density but reflects the decreased number of remaining viable and proliferating tumour cells due to perhaps cell and tissue destruction releasing proteins and/or metals that cause T1 relaxation. ΔT1 is a highly sensitive and specific predictor of response. This MRI method provides the opportunity to stratify a patient population during tumour therapy in the clinic. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Phyllodes tumors (PT) of the breast seem to get pre-operatively misdiagnosed as fibroadenomas resulting in inadequate resections and high local recurrence rates. MATERIALS AND METHODS: Data of 150 patients with PT of the breast managed from January, 2003 to February, 2013 were retrospectively analyzed. Statistical analysis performed using SPSS version 17 (Pearson Chi-square test and analysis of variance test for analysis). AIM: The aim of this study is to compare clinico-pathological profile and recurrence rates in patients with benign (B), borderline malignant (BL) and malignant (M) PT. RESULTS: In a total of 150 patients with PT (n = 77 B, n = 24 BL, n = 49 M), mean age was 36.92, 44.04 and 40.46 years respectively (P 0.015) and mean tumor size being 8.15 cm, 14.7 cm and 12.9 cm respectively (P 0.000). Pre-operatively cytology suggestive of PT in 24% patients with B PT and 63% in M PT; core tissue biopsy suggestive of PT in 85.4% patients with B PT and 100% in M PT. Recurrence seen in 34.7% out of which 32.7% were post-lumpectomy performed elsewhere. Majority of B PT had lumpectomy (49.3%)/ wide local excision (WLE, 31.2%) compared with M PT where 55.1% had simple mastectomy (SM) due to large tumor size. Local recurrence was more in M PT (53%) compared with B PT (20%). We found recurrence rates in L (39.3%) compared with WLE (27.3%) and SM (33.9%) (P 0.049). CONCLUSIONS: Larger tumor size, incomplete resection and M/BL histology predicted higher recurrence in PT. Core biopsy is much more accurate than fine needle cytology in the diagnosis. [ABSTRACT FROM AUTHOR]

Epidermal cysts rarely occur in the head and neck region as compared to the dermoid cysts and when they do occur in this region, they present in the floor of the mouth. We are reporting a rare case of an epidermal cyst in the floor of the mouth, with a brief review of the literature. [ABSTRACT FROM AUTHOR]

Objectives: To describe causes of discordant or negative parathyroid ultrasound and to assess factors influencing them. Materials and Methods: Retrospective review of patients who underwent parathyroidectomy between 2000 and 2012 was done. Imaging findings were compared with operative findings and pathology to identify discrepant (n=60; 32 negative, 28 incorrect) parathyroid ultrasounds. Results: Fifty (83.3%) patients had parathyroid adenoma, of which 10 (16.6%) were ectopic and three were double adenomas; 8 (13.3%) had multigland hyperplasia and two had parathyroid carcinoma. Discrepant reports were due to incorrect localisation in 8 (13.3%); difficulty in differentiating thyroid from parathyroid lesion in 12 (20%); large and small size in two and three patients, respectively; overcall in 5 (8.3%) and satisfaction of search in 7 (11.7%) patients. There was significant correlation between presence of multi-nodular goitre and incorrect reports (χ(2)=4.112, p=0.04). Experience of ultrasound operators performing initial and second look ultrasound was significantly different (p<0.0001). Second look ultrasound was concordant with surgical findings in 39(65%) patients; 21 (66%) patients with initially negative ultrasound and four out of five extra-mediastinal ectopic lesions. Ten patients with negative initial ultrasound had elongated parathyroid lesion. Scintigraphy was concordant in 44 (73.3%) patients and nine were ectopic. Conclusion: Second look ultrasound performed by experienced operator for negative or discordant initial ultrasound of parathyroid is a useful strategy which will improve the accuracy of parathyroid ultrasound. Being able to differentiate thyroid from parathyroid lesion is a factor which will influence performance of parathyroid ultrasound. [ABSTRACT FROM AUTHOR]

Neuroibromatosis type 1 is the most common phakomatoses and is inherited in autosomal dominant fashion with complete penetrance. Secondary hypertension is common in these patients due to various causes including adrenal tumors. Pheochromocytoma is a rare catecholamine producing tumor seen in 0.5% to 5% of patients with neuroibromatosis. The combination of pheochromocytoma with neuroibromatosis is rarely reported in the literature. We recently encountered an elderly lady with this combination who successfully underwent adrenalectomy. We report the case for the uncommon occurrence and to highlight the relevant literature review about pheochromocytoma in neuroibromatosis. [ABSTRACT FROM AUTHOR]

de Vries W, de Langen ZJ, Aronson DC, Hulscher JBF, Peeters PMJG, Jansen-Kalma P, Verkade HJ also on behalf of NeSBAR. Mortality of biliary atresia in children not undergoing liver transplantation in the Netherlands. Pediatr Transplantation 2011: 15:176-183. © 2010 John Wiley & Sons A/S. In order to further improve the outcome of BA, we characterized the mortality of BA patients who did not undergo OLT in the Netherlands, and compared our results with international data. For this purpose, we analyzed the causes of mortality of non-transplanted BA patients before the age of five yr, using the NeSBAR database. To evaluate trends in mortality, we compared the cohort 1987-1996 (n = 99) with 1997-2008 (n = 111). We compared clinical condition at OLT assessment with available international data, using the PELD-score. Mortality of non-transplanted BA children was 26% (26/99) in 1987-1996 and 16% (18/111) in 1997-2008 (p = 0.09). Sepsis was the prevailing direct cause of death (30%; 13/44). PELD-scores at the time of assessment were higher in non-transplanted BA patients (median 20.5; range 13-40) compared with international data (mean/median between 11.7 and 13.3). Based on our national data, we conclude that pretransplant mortality of BA patients is still considerable, and that sepsis is a predominant contributor. Our results strongly indicate that the prognosis of patients with BA in the Netherlands can be improved by earlier listing of patients for OLT and by improving pretransplant care. [ABSTRACT FROM AUTHOR]

Solid tumors have a raised interstitial fluid pressure (IFP) due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV) determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days) or later (6 or 7 days) lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P ≤ .005) correlated with late changes in tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to assess the outcome of liver resections in the elderly in a matched control analysis.Patients and Methods: From a prospective single center database of 628 patients, 132 patients were aged 60 years or over and underwent a primary major liver resection. Of these patients, 93 could be matched one-to-one with a control patient, aged less than 60 years, with the same diagnosis and the same type of liver resection. The mean age difference was 16.7 years.Results: Patients over 60 years of age had a significantly higher American Society of Anaesthesiologists (ASA) grade. All other demographics and operative characteristics were not different. In-hospital mortality and morbidity were higher in the patients over 60 years of age (11% versus 2%, p = 0.017 and 47% versus 31%, p = 0.024). One-, 3-, and 5-year survival rates in the patients over 60 years of age were 81%, 58%, and 42%, respectively, compared to 90%, 59%, and 42% in the control patients (p = 0.558). Unified model Cox regression analysis showed that resection margin status (hazard ratio 2.51) and ASA grade (hazard ratio 2.26), and not age, were determining factors for survival.Conclusion: This finding underlines the important fact that in patient selection for major liver resections, ASA grade is more important than patient age. [ABSTRACT FROM AUTHOR]

Patupilone is a microtubule stabilizer (MTS) currently in clinical development. Here, we evaluate the anti-cancer activity in vitro and in vivo in comparison to paclitaxel and describe the pharmacokinetics (PK) of patupilone in tumor-bearing nude mice and rats. The potency in vitro of patupilone and two other MTS, paclitaxel and ixabepilone, was determined using human colon carcinoma cell lines with low (HCT-116, HT-29, RKO) and high (HCT-15) P-glycoprotein expression (P-gp), as well as two multi-drug resistance (MDR) model cell pairs, MCF7/ADR and KB-8511 cells and their respective drug-sensitive parental counterparts. The PK of patupilone was investigated in nude mice bearing HCT-15 or HT-29 xenografts and in rats bearing s.c. pancreatic CA20498 tumors or A15 glioma tumors. Anti-cancer activity in vivo was compared to that of paclitaxel using three different human tumor colon models. The retention and efficacy of patupilone was compared in small and large HT-29 xenografts whose vascularity was determined by non-invasive magnetic resonance imaging. Patupilone was highly potent in vitro against four different colon carcinoma cell lines including those showing multi-drug-resistance. In contrast, paclitaxel and ixabepilone displayed significantly reduced activity with markedly increased resistance factors. In both rats and mice, a single i.v. bolus injection of patupilone (1.5–4 mg/kg) rapidly distributed from plasma to all tissues and was slowly eliminated from muscle, liver and small intestine, but showed longer retention in tumor and brain with no apparent elimination over 24 h. Patupilone showed significant activity against three human colon tumor models in vivo, unlike paclitaxel, which only had activity against low P-gp expressing tumors. In HT-29 tumors, patupilone activity and retention were independent of tumor size, blood volume and flow. The high potency of patupilone, which is not affected by P-gp expression either in vitro or in vivo, and favorable PK, independent of tumor vascularity, suggest that it should show significant activity in colorectal cancer and in other indications where high P-gp expression may compromise taxane activity. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the localization and management of patients with pancreatic insulinomas and determine the most effective localization and surgical techniques in the presence of significant financial constraints in the patient population. We retrospectively reviewed the case records of 18 patients with insulinomas treated at our institution over a period of 10 years. The medical records were reviewed for demographic data, clinical presentation, biochemistry, details of localization studies, intraoperative findings, postoperative outcome, and long-term follow-up. The sensitivities of the various localization procedures were calculated using the intraoperative findings as the gold standard. There were 10 men and 8 women in the study, with a median age of 43 years. All patients underwent a supervised 72-hour fast and developed symptomatic hypoglycemia within 48 hours. An average of 1.9 localization procedures was performed per patient. Computed tomography (CT) had a sensitivity of 62% and specificity of 100%. Magnetic resonance imaging and digital subtraction angiography had specificities of 85% and 100%, respectively, with a specificity of 66% and 50%, respectively. Fourteen patients underwent surgery. Intraoperatively the excised tumor was palpable in nine patients, and all patients had postoperative euglycemia. In five patients the tumor was not palpable during the time of surgery; three of these patients underwent blind distal pancreactomy, with two patients having persistent hypoglycemia during the postoperative period. Two patients had a negative exploratory laparotomy. Patients with a surgical cure were followed up for a mean period of 24 months. On the background of financial constraints in connection with patient care, CT scanning is a cost-effective option with good specificity. Intraoperative palpation of the tumor and enucleation is the most effective technique for surgical cure. Blind distal pancreactomy is not advocated for tumors that are not localized intraoperatively. [ABSTRACT FROM AUTHOR]

No consensus exists regarding the optimal reconstruction of the cavo-caval anastomosis in piggyback orthotopic liver transplantation (PB-LT). The aim of this study was to analyze our experience with end-to-side (ES) cavo-cavostomy. Outcome parameters were patient and graft survival and surgical complications. During the period 1995–2002 146 full-size PB-LT in 137 adult patients were performed with ES cavo-cavostomy without the routine use of temporary portocaval shunt (TPCS). In 12 patients (8%) this technique was used for implantation of second or third grafts. Veno-venous bypass was not used in any case and TPCS was performed only in eight patients (6%). One-, three- and five-yr patient and graft survival were 84%, 79% and 75%, and 81%, 74% and 69%, respectively. The median number of intraoperative transfusion of packed red blood cells (RBC) was 2.0 (range 0–33) and 30% of the patients (n = 43) did not require any RBC transfusion. Surgical complications of various types were observed after 49 LT (34%) and none of the complications was specifically related to the technique of ES cavo-cavostomy. Our experience indicates that PB-LT with ES cavo-cavostomy is a safe procedure, can safely be performed without the routine use of a TPCS, has a very low risk of venous outflow obstruction and can also be used effectively during retransplantations. [ABSTRACT FROM AUTHOR]

Clinical trials of new cancer drugs should ideally include measurements of parameters such as molecular target expression, pharmacokinetic (PK) behavior, and pharmacodynamic (PD) endpoints that can be linked to measures of clinical effect. Appropriate PK/PD biomarkers facilitate proof-of-concept demonstrations for target modulation; enhance the rational selection of an optimal drug dose and schedule; aid decision-making, such as whether to continue or close a drug development project; and may explain or predict clinical outcomes. In addition, measurement of PK/PD biomarkers can minimize uncertainty associated with predicting drug safety and efficacy, reduce the high levels of drug attrition during development, accelerate drug approval, and decrease the overall costs of drug development. However, there are many challenges in the development and implementation of biomarkers that probably explain their disappointingly low implementation in phase I trials. The Pharmacodynamic/Pharmacokinetic Technologies Advisory committee of Cancer Research UK has found that submissions for phase I trials of new cancer drugs in the United Kingdom often lack detailed information about PK and/or PD endpoints, which leads to suboptimal information being obtained in those trials or to delays in starting the trials while PK/PD methods are developed and validated. Minimally invasive PK/PD technologies have logistic and ethical advantages over more invasive technologies. Here we review these technologies, emphasizing magnetic resonance spectroscopy and positron emission tomography, which provide detailed functional and metabolic information. Assays that measure effects of drugs on important biologic pathways and processes are likely to be more cost-effective than those that measure specific molecular targets. Development, validation, and implementation of minimally invasive PK/PD methods are encouraged. [ABSTRACT FROM AUTHOR]

Miyamoto S, Polak WG, Geuken E, Peeters PMJG, de Jong KP, Porte RJ, van den Berg AP, Hendriks HG, Slooff MJH. Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults.Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00278.x© Blackwell Munksgaard, 2004The aim of this study is to analyse a single centre's experience with two techniques of liver transplantation (OLT), conventional (CON-OLT) and piggyback (PB-ES), and to compare outcome in terms of survival, morbidity, mortality and post-operative liver function as well as operative characteristics. A consecutive series (1994–2000) of 167 adult primary OLT were analysed. Ninety-six patients had CON-OLT and 71 patients had PB-ES. In PB-ES group two revascularization protocols were used. In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB-seq). In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB-sim). One-, 3- and 5-yr patient survival in the CON-OLT and PB-ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p = ns). Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (p = ns). Apart from the higher number of patients with cholangitis and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative liver and kidney function were not different between the two groups. The total operation time was not different between both groups (9.4 h in PB-ES vs. 10.0 h in CON-OLT), but in PB-ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (8.9 h vs. 10.7 h, 54 min vs. 63 min, 82 min vs. 114 min, 118 min vs. 160 min and 87 min vs. 114 min, respectively, p < 0.05). RBC use in the PB-ES group was lower compared to the CON-OLT group (4.0 min vs. 10.0 units, p < 0.05). Except for WIT and REVT there were no differences in operative characteristics between PB-Sim and PB-Seq groups. The WIT was significantly longer in PB-Sim group compared with PB-Seq group (64 min vs. 50 min, p < 0.05); however REVT was significantly shorter in PB-Sim group (64 min vs. 97 min, p < 0.05). Results of this study show that both techniques are comparable in survival and morbidity; however PB-ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use. In the PB-ES group there seems to be no adavantage for any of the revascularization protocols. [ABSTRACT FROM AUTHOR]

The partitioning of resources between different plant organs and compounds is an important determinant of crop quality. We are attempting to change resource partitioning in crop plants by manipulating the cellular mechanisms involved in metabolite sensing and signalling. One of the proteins involved is SnRK1 (sucrose nonfermenting-1-related protein kinase 1), so-called because of its homology and functional similarity with sucrose non-fermenting 1 (SNF1) of yeast. SnRK1 is a protein kinase that plays a key role in the global control of plant carbon metabolism. Here we review studies on the characterisation of SnRK1 gene families, SnRK1 regulation and function, and the identification of SnRK1-interacting proteins. We also describe some potential applications of manipulating SnRK1 activity, including controlling sprouting in stored potato tubers, inducing male sterility in barley and increasing sterol levels in oilseeds. [ABSTRACT FROM AUTHOR]

1. We studied whole-ecosystem metabolism in eight streams from several biomes in North America to identify controls on the rate of stream metabolism over a large geographic range. The streams studied had climates ranging from tropical to cool-temperate and from humid to arid and were all relatively uninfluenced by human disturbances. 2. Rates of gross primary production (GPP), ecosystem respiration (R) and net ecosystem production (NEP) were determined using the open-system, two-station diurnal oxygen change method. 3. Three general patterns in metabolism were evident among streams: (1) relatively high GPP with positive NEP (i.e. net oxygen production) in early afternoon, (2) moderate primary production with a distinct peak in GPP during daylight but negative NEP at all times and (3) little or no evidence of GPP during daylight and a relatively constant and negative NEP over the entire day. 4. Gross primary production was most strongly correlated with photosynthetically active radiation (PAR). A multiple regression model that included log PAR and stream water soluble reactive phosphorus (SRP) concentration explained 90% of the variation in log GPP. 5. Ecosystem respiration was significantly correlated with SRP concentration and size of the transient storage zone and, together, these factors explained 73% of the variation in R. The rate of R was poorly correlated with the rate of GPP. 6. Net ecosystem production was significantly correlated only with PAR, with 53% of the variation in log NEP explained by log PAR. Only Sycamore Creek, a desert stream in Arizona, had positive NEP (GPP: R > 1), supporting the idea that streams are generally net sinks rather than net sources of organic matter. 7. Our results suggest that light, phosphorus concentration and channel hydraulics are important controls on the rate of ecosystem metabolism in streams over very extensive geographic areas. [ABSTRACT FROM AUTHOR]

Unlabelled: The prerequisite for liver transplantation as a therapeutic option for inherited metabolic diseases should be that the enzyme defect, being responsible for the major clinical (hepatic and/or extra-hepatic) abnormalities, is localised in the liver. Furthermore, no adequate dietary or pharmacological treatment should be available or such treatment should have an unacceptable influence on the quality of life. We report an infant, who developed end-stage liver disease with persistent lactic acidaemia in his first months of life. Analysis of the mitochondrial respiratory chain in liver tissue revealed a combined partial complex I and IV deficiency. No extra-hepatic involvement could be demonstrated by careful screening for multiple organ involvement, including analysis of the mitochondrial respiratory chain in muscle tissue and cultured skin fibroblasts. The boy received a reduced size liver graft at the age of 8 months. He recovered successfully. Almost 5 years after transplantation he is in good clinical condition. No clinical or biochemical signs of any organ dysfunction have been demonstrated. The considerations on which basis it was decided that there was no contra-indication to perform liver transplantation in this patient are discussed.Conclusion: The possibility of a mitochondrial respiratory chain deficiency should be considered in liver disease of unknown origin prior to liver transplantation. Liver transplantation is a therapeutic option in mitochondrial respiratory chain deficiency-based end-stage liver disease provided that extra-hepatic involvement is carefully excluded. [ABSTRACT FROM AUTHOR]

2-carboxy-D-ambinitol-1-phosphate (CA1P) bound to Rubisco either in leaf extracts or after purification can be displaced by SO42- ions. Thus, treatment of leaf extracts with a buffer containing 200 mol m-3 SO42- displaces any bound CA1P and enables measurement of maximum carboxylation potential. In tobacco leaves, the activity following treatment with SO42- ions ('maximal activity') is greater than the total Rubisco activity. The ratio of the two activities altered in a dynamic way with fluctuations in irradiance. Even in species which do not produce significant amounts of CA1P, the maximal activity greatly exceeded the total activity. Anion exchange separation of components in acid extracts confirmed the absence of CA1P in tobacco leaves harvested above an irradiance of 300 μmol quanta m-2s-1, but the presence of another inhibitor of Rubisco. These results are consistent with the regulation of Rubisco activity by inhibitors other than CA1P which, like CA1P, can be displaced by SO42- ions. [ABSTRACT FROM AUTHOR]

Here we report on the molecular defect that leads to a deficiency of lipoprotein lipase (LPL) activity in a proband of Dutch descent. Southern-blot analysis of the LPL gene from the patient did not reveal any major DNA rearrangements. Sequencing of polymerase-chain-reaction-amplified DNA revealed that the proband is a homozygote for G725C, resulting in a substitution of Pro157 for Arg. This substitution alters a restriction site for PvuII, which allowed rapid identification of the mutant allele in family members. Site-directed mutagenesis and transient expression of the mutant LPL in COS cells produced an enzymaticany inactive protein, establishing the functional significance of this mutation. This naturally occurring mutation which alters the Pro157 adjacent to Asp156 of the proposed catalytic triad, indicates that this region of the protein is indeed crucial for LPL catalytic activity. [ABSTRACT FROM AUTHOR]

Background Pheochromocytomas are diagnosed in <1% of patient evaluated for hypertension. Methodology A retrospective analysis of case records of those patients with histopathologically confirmed pheochromocytoma in our hospital from 1976–2006 [30 YEARS] was conducted. Result A total of 123 patients were diagnosed during this period. The median age at presentation was 31 years (range 9–71) with a male to female sex distribution of 75% and 36%. 80% were hypertensive at the time of diagnosis. Headache(84%), palpitations(64%) and sweating(60%) are the most common presenting complaints.Tachycardia [>100 per minute]were seen in 31%. Hypertensive changes in eyes were seen in 87%. In ECG, QTc prolongation in 26%, left ventricular hypertrophy in 30%. Diabetes mellitus/IGT was seen in 35%. Elevated urinary VMA (24 hrs) was seen in 93% when done on 3 consecutive days. MIBG was positive in 85%. Malignant pheochromocytoma was diagnosed by tumour invasion/metastasis seen 10.44%. Extra adrenal pheochromocytoma 18%, followed by bilateral pheochromocytoma in 11%. Hereditary pheochromocytoma in 13% which include 5 with Von Hippel Lindau and 6 with MEN. A median follow-up was 12 months (range 1–204) in which persistent hypertension was seen in 16%. Cholelithiasis in 7%. Conclusion In our case series the mean age (31 yrs) of presentation seems to be younger compared to other case series. 16% of our patients were asymptomatic at the time of presentation. Urinary VMA was elevated in 93% of patients when done in 3 consecutive samples. Extra adrenal pheo was common in our patients (18%). MIBG was false negative in 15% of those patients with pheochromocytoma. [ABSTRACT FROM AUTHOR]

Introduction Parathyroid carcinoma is a challenging problem to a surgeon and adjuvant radiotherapy is important to reduce the recurrence. Methods A retrospective review was conducted of all cases of parathyroid carcinoma from 1990–2006. 6 patients were identified. Results There was a male preponderance. Mean age of presentation was 49 years. The clinical presentation was similar to benign primary hyperparathyroidism except for the presence of palpable nodule in 80% of patients with carcinoma compared to 11% among patients with benign primary hyperparathyroidism. One patient had chronic pancreatits propably secondary to hyperparathyroidism. All patients had hypercalcaemia with elevated serum PTH levels and no significant difference compared to benign hyperparathyroidism. Surgery was done in all. Local metastasis to the cervical lymph nodes was seen in 33% off patients. The tumors showed a high predilection to the inferior parathyroid glands.. All subjects underwent radiotherapy with cobalt at mean dose of 50 cGy. The mean duration of recurrence was about 2 years. 50% had local recurrence, 2 had recurrent tumor excision including one from vocal cord. Bony metastasis was found in one as evidenced by hot spots in sestamibi scan. 2 of the 6 died, both of them had unrelated disease as cause of death. 1 lost to follow up. Conclusion Parathyroid carcinoma constitutes around 2–3% of patients. In the presence of a palpable nodule, chance of being malignant should be kept in mind. Recurrence rate can be reduced by post operative external radiotherapy. [ABSTRACT FROM AUTHOR]

We investigate the carrier dynamics in nickel-titanium (Ni-Ti) alloy thin films using terahertz transmission spectroscopy. Analyzing the power transmission data and the transmitted waveforms, we obtained the alloy resistivity as a function of Ti concentration. Sharp changes in the resistivity were observed at the Ti fractions of 22%, 44%, and 62%, indicating that structural disorder is greatly enhanced when the alloy undergoes a phase transition. [ABSTRACT FROM AUTHOR]

Dysregulated arousal often accompanies neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism spectrum disorder. Recently, we have found that adolescent homozygous Brattleboro (Hom) rats, which contain a mutation in the arginine vasopressin (AVP) gene, exhibit lower behavioral arousal than their heterozygous (Het) littermates in the open field test. This hypoaroused phenotype could be due to loss of AVP in magnocellular cells that supply AVP to the peripheral circulation and project to limbic structures or parvocellular cells that regulate the stress axis and other central targets. Alternatively, hypoarousal could be a side effect of diabetes insipidus – polydipsia and polyuria seen in Hom rats due to loss of AVP facilitation of water reabsorption in the kidney. We developed a viral-rescue approach to "cure" magnocellular AVP cells of their Brattleboro mutation. Infusion of a recombinant adeno-associated virus (rAAV) containing a functional Avp gene and promoter (rAAV-AVP) rescued AVP within magnocellular cells and fiber projections of the paraventricular nucleus of the hypothalamus (PVN) of male and female adolescent Hom rats. Furthermore, water intake was markedly reduced, ameliorating the symptoms of diabetes insipidus. In contrast, open field activity was unaffected. These findings indicate that the hyporaoused phenotype of adolescent Hom rats is not due to the loss of AVP function in magnocellular cells or a side effect of diabetes insipidus, but favors the hypothesis that central, parvocellular AVP mechanisms underlie the regulation of arousal during adolescence. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the mutational analysis of RET proto-oncogene in medullary thyroid carcinoma patients and carriers who are at risk in India.

Background: Effective chemotherapy rapidly reduces the spin-lattice relaxation of water protons (T1) in solid tumours and this change (ΔT1) often precedes and strongly correlates with the eventual change in tumour volume (TVol). To understand the biological nature of ΔT1, we have performed studies in vivo and ex vivo with the allosteric mTOR inhibitor, everolimus.Methods: Mice bearing RIF-1 tumours were studied by magnetic resonance imaging (MRI) to determine TVol and T1, and MR spectroscopy (MRS) to determine levels of the proliferation marker choline and levels of lipid apoptosis markers, prior to and 5 days (endpoint) after daily treatment with vehicle or everolimus (10 mg/kg). At the endpoint, tumours were ablated and an entire section analysed for cellular and necrotic quantification and staining for the proliferation antigen Ki67 and cleaved-caspase-3 as a measure of apoptosis. The number of blood-vessels (BV) was evaluated by CD31 staining. Mice bearing B16/BL6 melanoma tumours were studied by MRI to determine T1 under similar everolimus treatment. At the endpoint, cell bioluminescence of the tumours was measured ex vivo.Results: Everolimus blocked RIF-1 tumour growth and significantly reduced tumour T1 and total choline (Cho) levels, and increased polyunsaturated fatty-acids which are markers of apoptosis. Immunohistochemistry showed that everolimus reduced the %Ki67+ cells but did not affect caspase-3 apoptosis, necrosis, BV-number or cell density. The change in T1 (ΔT1) correlated strongly with the changes in TVol and Cho and %Ki67+. In B16/BL6 tumours, everolimus also decreased T1 and this correlated with cell bioluminescence; another marker of cell viability. Receiver-operating-characteristic curves (ROC) for everolimus on RIF-1 tumours showed that ΔT1 had very high levels of sensitivity and specificity (ROCAUC = 0.84) and this was confirmed for the cytotoxic patupilone in the same tumour model (ROCAUC = 0.97).Conclusion: These studies suggest that ΔT1 is not a measure of cell density but reflects the decreased number of remaining viable and proliferating tumour cells due to perhaps cell and tissue destruction releasing proteins and/or metals that cause T1 relaxation. ΔT1 is a highly sensitive and specific predictor of response. This MRI method provides the opportunity to stratify a patient population during tumour therapy in the clinic. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Radioactive iodine ablation does not prevent recurrences in patients with papillary thyroid microcarcinoma," by H. J. Kim and colleagues in the 2012 issue.

Introduction: Insulinomas are rare tumours with an annual incidence of 1 to 4 per million persons and about 10% of them have multiple endocrine neoplasia-1 (MEN-1). About 70-80% of insulinomas in MEN-1 are multiple with a 21% recurrence rate. Hence it is important to undertake a thorough preoperative and intraoperative screening to avoid incomplete surgeries. Objective: Profile the patients of Insulinoma with MEN-1 in a tertiary care centre. Materials and Methods: Clinical, biochemical and radiological data of all the patients diagnosed to have Insulinoma with MEN-1 from May-2011 to April 2012 was analysed. Results: There were 2 male and 1 female patients. The average duration of symptoms was 6 years and 2 had neuroglycopenic symptoms. Insulinoma was localized in all patients with MRI abdomen and endoscopic ultrasonography. All had double lesions with recurrence in one patient. All had hyperparathyroidism, 2 had pituitary tumours among which 1 patient had a microprolactinoma and the other had acromegaly with associated thymic carcinoid, gastrinoma with liver metastasis, and non-functioning adrenal adenoma, 2 patients had collagenomas. Two were sporadic and 1 was familial with 3 family members having hyperparathyroidism. Two patients underwent excision successfully and the third patient deferred surgical intervention. Conclusion: Screening for MEN-1 should be done in all patients with Insulinoma. Collagenomas are an important clue to MEN-1. Management of insulinoma in MEN-1 is a challenge in view of the multicentricity and increased risk of recurrence. [ABSTRACT FROM AUTHOR]