Are we overtreating patients with malignant colorectal polyps? A 5-year review of the ACPGBI position statement.

INTRODUCTION: In 2013, The Association of Coloproctology of Great Britain and Ireland (ACPGBI) issued a position statement regarding management of malignant polyps. We reviewed the management of endoscopically resected malignant colorectal polyps in a district general hospital to evaluate whether patients were being overtreated as per these guidelines. METHODS: All patients who underwent a complete, non-piecemeal endoscopic removal of a malignant polyp between October 2013 and September 2018 were studied. Polyps were risk stratified for residual disease and followed up as per the ACPGBI. Patients were divided into two groups based on management after polypectomy. Primary outcome measured was the presence of residual tumour or involved lymph nodes in the resection specimen. Secondary outcomes included complications and recurrence. RESULTS: Thirty-three patients were included: 21 in the non-operative group (NOG) and 12 in the operative group (OG). The ACPGBI risk score in the NOG varied between 1 and over 4 compared with the OG who all scored over 4. Two patients in the OG (16%) demonstrated residual disease. Five patients suffered a postoperative complication. No recurrences were noted in the OG and one in the NOG. CONCLUSION: Our findings against a backdrop of the available literature suggest that the risk of residual disease after malignant polypectomy may not be as high as stated by the ACPGBI. As a result, there is a risk of overtreating patients and exposing them to the significant complications of surgery if careful consideration is not exercised.

Quality of life in breast cancer survivors: An assessment of international breast cancer dragon boat racers.

Resistance exercise is deemed safe for women recovering from conventional breast cancer therapies but few clinicians are aware that dragon boat racing, as a form of resistive exercise, is available to the breast cancer community. The objectives of this study were to 1) increase clinician awareness of dragon boat racing (DBR) in breast cancer survivors as a community-based physical activity, and 2) evaluate quality of life (QOL) in breast cancer survivors with or without lymphedema who participate in DBR. This prospective, observational study surveyed 1,069 international breast cancer dragon boat racers from eight countries to compare function, activity, and participation in women with and without selfreported lymphedema using the Lymph-ICF questionnaire. Seventy-one percent of women (n=758) completed the questionnaires. Results revealed significantly higher Lymph-ICF scores in the lymphedema participants, signifying reduced QOL, when compared to the nonlymphedema participants (p<0.05), except for "go on vacation" for which no statistical difference was reported (p=0.20). International breast cancer survivors with lymphedema participating in DBR at an international competition had reduced function, limited activity, and restricted participation compared to participants without lymphedema. Clinicians should consider utilizing DBR as a community-based activity to support exercise and physical activity after a breast cancer diagnosis.

Advanced-stage mycosis fungoides: role of the signal transducer and activator of transcription 3, nuclear factor-κB and nuclear factor of activated T cells pathways.

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.

PRP­1 significantly decreases the ALDHhigh cancer stem cell population and regulates the aberrant Wnt/ß­catenin pathway in human chondrosarcoma JJ012 cells.

Chondrosarcomas are malignant bone tumors refractory to chemotherapy and radiation treatment; thus, novel therapeutic strategies are required. Proline­rich polypeptide 1 (PRP­1) has previously demonstrated antitumor properties in chondrosarcoma. To further investigate the role of PRP­1 in chondrosarcoma cells, its effects on cancer stem cell (CSC) populations were determined by analyzing aldehyde dehydrogenase (ALDH) activity, an established marker of CSCs, in association with regulation of the Wnt/ß­catenin signaling. A significant decrease in ALDHhigh CSCs was observed following treatment of chondrosarcoma JJ012 cells with PRP­1. For RT2 profiler PCR array analysis of Wnt/ß­catenin signaling genes, cells were sorted into: i) Bulk JJ012 cells; ii) ALDHhigh cells sorted from untreated JJ012 cells (ALDHhigh­untreated); and iii) ALDHlow cells sorted from PRP­1­treated JJ012 cells (ALDHlow­PRP­1). The expression levels of Wnt/ß­catenin signaling genes were determined to be downregulated in the ALDHhigh­untreated cells and upregulated in ALDHlow­PRP­1 cells when compared to the bulk JJ012 cells. Additionally, two important oncogenes involved in this pathway, MMP7 and CCND2, were found to be downregulated in the ALDHlow­PRP­1 cells. Immunocytochemistry demonstrated the localization of ß­catenin in the nuclei of the PRP­1­treated cells. Western blotting indicated increased ß­catenin expression in the ALDHlow­PRP­1 cells compared with the bulk JJ012 cells. Analysis of the cytoplasmic and nuclear fractions of cells treated with increasing concentrations of PRP­1 and ß­catenin nuclear translocation inhibitor CGP57380, suggested the nuclear translocation of ß­catenin following PRP­1 treatment. In addition, treatment of JJ012 cells with a specific ALDH inhibitor, diethylaminobenzaldehyde, and PRP­1 resulted in a significant decrease in cytoplasmic ß­catenin protein expression. This indicated that ALDH inactivation may be associated with the nuclear translocation of ß­catenin. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway has been previously documented. The findings of the present study support the notion that Wnt/ß­catenin activation may serve a differential role in sarcomas, limiting tumor progression in association with decreased CSC activity.

The role of cognitive training in endourology: a randomised controlled trial. / El papel de la formación cognitiva en la endourología: un ensayo controlado aleatorizado.

INTRODUCTION: Cognitive training is an important training modality which allows the user to rehearse a procedure without physically carrying it out. This has led to recent interests to incorporate cognitive training within surgical education but research is currently limited. The use of cognitive training in surgery is not clear-cut and so this study aimed to determine whether, relative to a control condition, the use of cognitive training improves technical surgical skills on a ureteroscopy simulator, and if so whether one cognitive training method is superior. METHODS: This prospective, comparative study recruited 59 medical students and randomised them to one of three groups: control- simulation training only (n=20), flashcards cognitive training group (n=20) or mental imagery cognitive training group (n=19). All participants completed three tasks at baseline on the URO Mentor simulator followed by the cognitive intervention if randomised to receive it. Participants then returned to perform an assessment task on the simulator. Outcome measures from the URO Mentor performance report was used for analysis and a quantitative survey was given to all participants to assess usefulness of training received. RESULTS: This study showed cognitive training to have minimal effects on technical skills of participants. The mental imagery group had fewer laser misfires in the assessment task when compared to both control and flashcards group (P=.017, P=.036, respectively). The flashcards group rated their preparation to be most useful when compared to control (P=.0125). Other parameters analysed between the groups did not reach statistical significance. Cognitive training was found to be feasible and cost effective when carried out in addition to simulation training. CONCLUSION: This study has shown that the role of cognitive training within acquisition of surgical skills is minimal and that no form of cognitive training was superior to another. Further research needs to be done to evaluate other ways of performing cognitive training.

Trends in survival for teenagers and young adults with cancer in the UK 1992-2006.

BACKGROUND: Although relatively rare, cancer in teenagers and young adults (TYA) is the most common disease-related cause of death and makes a major contribution to years of life lost in this age group. There is a growing awareness of the distinctive needs of this age group and drive for greater understanding of how outcomes can be improved. We present here the latest TYA survival trends data for the United Kingdom (UK). METHODS: Using national cancer registry data, we calculated five-year relative survival for all 15-24 year olds diagnosed with cancer or a borderline/benign CNS tumour in the UK during the periods 1992-1996, 1997-2001 and 2002-2006. We analysed trends in survival for all cancers combined and for eighteen specified groups that together represent the majority of TYA cancers. We compared our data with published data for Europe, North America and Australia. RESULTS: Five-year survival for all cancers combined increased from 75.5% in 1992-1996 to 82.2% in 2002-2006 (P<0.001). Statistically significant improvements were seen for all disease groups except osteosarcoma, rhabdomyosarcoma, non-gonadal and ovarian germ cell tumours and ovarian and thyroid carcinomas. During the earliest time period, females had significantly better survival than males for five of the twelve non-gender-specific disease groups. By the latest period, only melanomas and non-rhabdomyosarcoma soft tissue sarcomas had differential survival by gender. Survival in the UK for the most recent period was generally similar to other comparable countries. CONCLUSION: Five-year survival has improved considerably in the UK for most cancer types. For some disease groups, there has been little progress, either because survival already approaches 100% (e.g. thyroid carcinomas) or, more worryingly for some cancers with poor outcomes, because they remain resistant to existing therapy (e.g. rhabdomyosarcoma). In addition, for a number of specific cancer types and for cancer as a whole males continue to have worse outcomes than females.

Excessive range of statin dose in Western Australian primary care.

BACKGROUND: Statins are very effective in reducing coronary disease and ischaemic stroke but guidelines although evolving have not been clear on statin dose. AIM: To audit and review community statin prescribing. METHODS: A retrospective audit of the type and dose of statin dispensed was undertaken at five pharmacies in and around Perth, the capital city of Western Australia. Patients were de-identified. RESULTS: Statins made up 6.5% of all prescriptions. Statin dose when adjusted for different potency effectively varied 64-fold between patients. Rosuvastatin and atorvastatin accounted for 79% of prescriptions, at a mean dose of 10 times the effective dose 50. CONCLUSION: The extraordinarily wide variation in statin dose is at odds with the more consistent doses of other drugs used in the management of arterial disease. Unnecessarily high statin dosing increases side-effects and may not improve clinical outcomes appreciably. Rational prescribing of statins based on the pharmacodynamic evidence, with lower doses in most patients, combined with close attention to reduction of smoking, blood pressure and weight, is likely to reduce arterial disease most efficiently and safely.

Development of Autoimmune-Mediated ß Cell Failure After Total Pancreatectomy With Autologous Islet Transplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is performed for definitive treatment of chronic pancreatitis; patients are not diabetic before surgery, or have C-peptide positive pancreatogenous diabetes. Thus, TPIAT recipients are not traditionally considered at risk for autoimmune loss of the islet graft. We describe a 43-year-old female who underwent TPIAT with high mass islet graft of 6031 IEQ/kg, with no evidence of presurgical ß cell autoimmunity who developed type 1 diabetes within the first year after TPIAT, resulting in complete loss of beta cell function. The patient had positive GAD and insulin autoantibodies at 1 year and 18 months after TPIAT, not present prior, and undetectable C-peptide after mixed meal and intravenous glucose tolerance testing at 18 months. Glucagon secretion was preserved, suggesting the transplanted alpha cell mass was intact. HLA typing revealed a DR3/DR4 class II haplotype. This case highlights the need to consider de novo type 1 diabetes in patients with unexpected islet graft failure after TPIAT.

Valorisation of used cooking oil sludge by codigestion with swine manure.

The addition of lipid wastes to the digestion of swine manure was studied as a means of increasing biogas production. Lipid waste was obtained from a biodiesel plant where used cooking oil is the feedstock. Digestion of this co-substrate was proposed as a way of valorising residual streams from the process of biodiesel production and to integrate the digestion process into the biorefinery concept. Batch digestion tests were performed at different co-digesting proportions obtaining as a result an increase in biogas production with the increase in the amount of co-substrate added to the mixture. Semi-continuous digestion was studied at a 7% (w/w) mass fraction of total solids. Co-digestion was successful at a hydraulic retention time (HRT) of 50 d but a decrease to 30 d resulted in a decrease in specific gas production and accumulation of volatile and long chain fatty acids. The CH4 yield obtained was 326 ± 46 l/kg VSfeed at an HRT of 50 d, while this value was reduced to 274 ± 43 l/kg VSfeed when evaluated at an HRT of 30 d. However these values were higher than the one obtained under batch conditions (266 ± 40 l/kg VSfeed), thus indicating the need of acclimation to the co-substrate. Despite of operating at low organic loading rate (OLR), measurements from respirometry assays of digestate samples (at an HRT of 50 d) suggested that the effluent could not be directly applied to the soil as fertiliser and might have a negative effect over soil or crops.

Aqueous cigarette smoke extract induces a voltage-dependent inhibition of CFTR expressed in Xenopus oocytes.

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel inhabits the apical membrane of airway epithelia, where its function is essential for mucus hydration, mucociliary clearance, and airway defense. Chronic obstructive pulmonary disease (COPD), most often a consequence of cigarette smoke (CS) exposure, affects 15 million persons in the US. Clinically, COPD is characterized by many of the salient features of cystic fibrosis lung disease, where CFTR is either absent or reduced in function. CS is an acidic aerosol (pH 5.3 to 6.3) reported to contain over 4,000 constituents. Acute CS exposure has been reported to decrease airway transepithelial voltage in vivo and short-circuit current in vitro; however, the mechanistic basis of these effects is uncertain. The goal of the studies described here was to develop a bioassay to characterize the effects of aqueous CS preparations on the channel function of CFTR. We studied aqueous CS extract (CSE) prepared in our laboratory, as well as commercial cigarette smoke condensate (CSC) in Xenopus oocytes expressing human CFTR. Application of CSE at pH 5.3 produced a reversible, voltage-dependent inhibition of CFTR conductance. CSE neutralized to pH 7.3 produced less inhibition of CFTR conductance. Serial dilution of CSE revealed a dose-dependent effect at acidic and neutral pH. In contrast, CSC did not inhibit CFTR conductance in oocytes. We conclude that one or more components of CSE inhibits CFTR in a manner similar to diphenylamine-2-carboxylate, a negatively charged, open-channel blocker.

The state of US health, 1990-2010: burden of diseases, injuries, and risk factors.

IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

Relation of chemokines to BMI and insulin resistance at ages 18-21.

OBJECTIVE: In obesity, adipose tissue becomes a significant source of chemokines and inflammatory cytokines that are associated with chronic systemic low-grade inflammation and may lead to insulin resistance. Studies in children have mainly focused on inflammatory cytokines and there are limited data for chemokines in adolescents and young adults. We studied the relation of chemokines to cardiovascular (CV)-risk factors, insulin resistance and adipocytokines in 18-21-year-old individuals. SUBJECTS AND DESIGN: Cross-sectional data collected in a cohort originally enrolled at mean age 13, with data for the present study obtained from 252 examined at age 18.7±0.1 years. METHODS: Multiple linear regression models were used to analyze the associations among chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein-1ß (MIP-1ß), visfatin and interleukin-8 (IL-8)) and between chemokines and body mass index (BMI), glucose, lipids, blood pressure (BP), insulin resistance (euglycemic hyperinsulinemic clamp) and adipocytokines (IL-6, TNF-α and adiponectin). RESULTS: Chemokine levels were significantly intercorrelated. Significant associations (P<0.05) with adjustment for age, race and sex included: MIP-1ß with waist circumference and IL-6, IL-8 with systolic BP and visfatin with IL-6. No other significant relations were found between the chemokines and the other variables. Further adjustment for BMI did not alter these conclusions. CONCLUSION: Considered in the context of prior studies in children and adults, these results suggest that in large part, the association between chemokines and CV risk or inflammatory factors does not appear to develop until adult life.

Hydrogen production from food wastes and gas post-treatment by CO2 adsorption.

The production of H(2) by biological means, although still far from being a commercially viable proposition, offers great promise for the future. Purification of the biogas obtained may lead to the production of highly concentrated H(2) streams appropriate for industrial application. This research work evaluates the dark fermentation of food wastes and assesses the possibility of adsorbing CO(2) from the gas stream by means of a low cost biomass-based adsorbent. The reactor used was a completely stirred tank reactor run at different hydraulic retention times (HRTs) while the concentration of solids of the feeding stream was kept constant. The results obtained demonstrate that the H(2) yields from the fermentation of food wastes were affected by modifications in the hydraulic retention time (HRT) due to incomplete hydrolysis. The decrease in the duration of fermentation had a negative effect on the conversion of the substrate into soluble products. This resulted in a lower amount of soluble substrate being available for metabolisation by H(2) producing microflora leading to a reduction in specific H(2) production. Adsorption of CO(2) from a gas stream generated from the dark fermentation process was successfully carried out. The data obtained demonstrate that the column filled with biomass-derived activated carbon resulted in a high degree of hydrogen purification. Co-adsorption of H(2)S onto the activated carbon also took place, there being no evidence of H(2)S present in the bio-H(2) exiting the column. Nevertheless, the concentration of H(2)S was very low, and this co-adsorption did not affect the CO(2) capture capacity of the activated carbon.

Short-term outcomes using the Christensen patient-specific temporomandibular joint implant system: a prospective study.

Thirty-one patients were assessed for changes in pain and maximal mouth opening (MMO) before and after total temporomandibular joint (TMJ) replacement. All prosthetic joint replacements used the Christensen fossa-eminence prosthesis system; 18 were unilateral and 13 bilateral. There were more women (n=22) than men (n=9), and their mean age was 45 years (women 46, range 18-74, and men 42, range 28-69). Indications for replacement included osteoarthritis, ankylosis, and "other". There were overall significant improvements in pain scores for the whole group at one year (95% CI 6.3-8.5 compared with 0.2-3.0) and for women alone (6.5 to 9.2 compared with -0.5 to 2.0). There were also significant improvements in pain scores in both those with osteoarthritis (95% CI 8.1 to 8.9 compared with -0.8 to 3.8) and the group with "other" diagnoses at the 12-month follow-up (95% CI 4.4 to 10.7 compared with -0.2 to 0.5). Finally, there was a significant improvement in MMO in the whole group at the time of 12-month follow-up (95% CI 15.8-23.5 compared with 24.0-32.3).

Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations.

The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of "other cancers" in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1-6.0) and stomach at 2.4 (95% CI 1.2-4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9-7.8) and prostate (RR 6.3, 95% CI 4.3-9.0) and uveal melanoma (RR 99.4, 95% CI 11.1-359.8) were confirmed. Possible new associations with oesophagus (RR 4.1, 95% CI 1.9-7.8) and stomach (RR 2.7, 95% CI 1.3-4.8) were detected but these findings should be treated with caution due to lower confirmation rates. In contrast to previous research a higher risk of prostate cancer was found in males with mutations in the BRCA2 OCCR region. The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1. New associations with upper gastro-intestinal malignancy need to be treated with caution and confirmed by large prospective studies.

A low frequency of pancreatic islet insulin-expressing cells derived from cord blood stem cell allografts in humans.

AIMS/HYPOTHESIS: We sought to establish if stem cells contained in cord blood cell allografts have the capacity to differentiate into insulin-expressing beta cells in humans. METHODS: We studied pancreases obtained at autopsy from individuals (n = 11) who had prior opposite-sex cord blood transplants to reconstitute haematopoiesis. Pancreatic tissue sections were stained first by XY-fluorescence in situ hybridisation and then insulin immunohistochemistry. Pancreases obtained at autopsy from participants without cord blood cell infusions served as controls (n = 11). RESULTS: In the men with prior transplant of female cord blood, there were 3.4 ± 0.3% XX-positive insulin-expressing islet cells compared with 0.32 ± 0.05% (p < 0.01) in male controls. In women with prior transplant of male cord blood cells we detected 1.03 ± 0.20% XY insulin-expressing islet cells compared with 0.03 ± 0.03 in female controls (p < 0. 001). CONCLUSIONS/INTERPRETATION: Cord blood stem cells have the capacity to differentiate into insulin-expressing cells in non-diabetic humans. It remains to be established whether these cells have the properties of beta cells.

Gitelman's syndrome: a rare presentation mimicking cauda equina syndrome.

We describe a case of bilateral weakness of the lower limbs, sensory disturbance and intermittent urinary incontinence, secondary to untreated Gitelman's syndrome, in a 42-year-old female who was referred with presumed cauda equina syndrome. On examination, the power of both legs was uniformly reduced, and the perianal and lower-limb sensation was altered. However, MRI of the lumbar spine was normal. Measurements of serum and urinary potassium were low and blood gas analysis revealed metabolic alkalosis. Her symptoms resolved following potassium replacement. We emphasise the importance of measurement of the plasma and urinary levels of electrolytes in the investigation of patients with paralysis of the lower limbs and suggest that they, together with blood gas analysis, allow the exclusion of unusual causes of muscle weakness resulting from metabolic disorders such as metabolic alkalosis.

Managing diabetes in cystic fibrosis.

Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in persons with cystic fibrosis (CF). As the life expectancy of persons with CF continues to increase, the need to proactively diagnose and aggressively treat CFRD and its potential complications has become more apparent. CFRD negatively impacts lung function, growth and mortality, making its diagnosis and management crucial in a population already at high risk for early mortality. Compared to type 1 and type 2 diabetes, CFRD is a unique entity, requiring a thorough understanding of its unique pathophysiology to facilitate the creation and utilization of an effective medical treatment plan. The physiology of CFRD is complex, likely consisting of a combination of insulin deficiency, insulin resistance and a genetic predisposition towards the development of diabetes. However, the hallmark of CFRD is insulin deficiency, necessitating the use of exogenous insulin as the mainstay of therapy. Insulin administration, in combination with a multidisciplinary team of health professionals with expertise in the care of patients with CF and CFRD, is the cornerstone of the care for these patients. The goals of treatment of the CFRD population are to reverse protein catabolism, maintain a healthy weight, and reduce acute and chronic diabetes complications. Creating a partnership between the treatment team and the patient is the ideal way to accomplish these goals and is essential for successful diabetes care.