Four-hour voiding observations detect neurogenic lower urinary tract dysfunction in neonates with anorectal malformation.

INTRODUCTION: Neurogenic lower urinary tract dysfunction (LUTD) has been reported in 20-50% of children with anorectal malformations (ARM). As neurogenic LUTD represents an inherent risk of renal deterioration and urinary tract infections, an early diagnosis is important. The gold standard for evaluating neurogenic LUTD involves invasive urodynamic testing but a useful addition should be an easy-to-perform, non-invasive method of screening. OBJECTIVE: In this study, we evaluate non-invasive 4 h voiding observations as a screening method for neurogenic LUTD in ARM children. STUDY DESIGN: Thirty-four patients with ARM, excluding those with perineal fistulas, were evaluated using both 4 h voiding observation and urodynamic testing before and after posterior sagittal anorectoplasty (PSARP) at median ages of 0.3 and 1.1 years. In the urodynamic assessment, the gold standard for neurogenic LUTD, nine children received the diagnosis, eight innate and one post-surgery. RESULTS: Five boys with a high urethral fistula and anomalies of the spinal cord had urodynamically diagnosed neurogenic LUTD, a dysfunction also identified in the 4 h voiding observations. The pattern was characterised both by an increase in the number of voiding and the number of interrupted voiding, urinary leakage and elevated residual urine (Figure). In three girls with a vestibular fistula and tethered cord, an urodynamic investigation identified suspected mild neurogenic LUTD. In the voiding observations, an abnormal voiding pattern was not as obvious in the girls as in the five males. One girl with cloaca showed signs of postsurgical denervation damage, which was easily identified in the 4 h voiding observations (high capacity and elevated residual urine). DISCUSSION: In the present study, gender differences in the severity of dysfunction reflected in the free voiding pattern in infants with ARM and neurogenic LUTD is probably the result of the different underlying causes of neurogenic LUTD in boys and girls. Boys with the condition have a congenital malformation of the caudal part of the spinal cord and girls a tethering of the cord. The most obvious limitation of the study was the low number of patients. Despite this, we consider the results worth reporting, since we found that results in the free voiding observations effectively confirmed what was established in the urodynamic investigations. CONCLUSION: In pre-PSARP patients, 4 h voiding observations can be used to screen for severe neurogenic LUTD requiring attention and treatment. When post-surgical denervation is suspected, the voiding observation is also a good method for indicating the diagnosis.

Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.

BACKGROUND: Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. METHODS: An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. RESULTS: Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. CONCLUSION: Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.

ANTECEDENTES: La cirugía de la aganglionosis colónica total (total colonic aganglionosis, TCA) está diseñada para preservar la continencia y lograr una calidad de vida satisfactoria. Este estudio evaluó un gran número de resultados clínicos y sociales. MÉTODOS: Se realizó un estudio internacional multicéntrico en ocho hospitales nórdicos en el que se incluyeron las historias clínicas de todos los pacientes nacidos con TCA entre 1987 y 2006. Se invitó a los pacientes y a sus cuidadores a responder una encuesta sobre la función intestinal, el crecimiento y las necesidades nutricionales, así como la repercusión social de la enfermedad a largo plazo. RESULTADOS: De un total de 116 pacientes, 5 (4,3%) habían fallecido y 102 respondieron la encuesta. Con una mediana de seguimiento de 12 años (rango 0,5-33), se había restablecido la continuidad intestinal en 75/102 (74%) a una mediana de edad de 11 meses (0,5-156). La mucosectomía con un manguito muscular corto y anastomosis ileoanal directa (short muscular cuff and straight ileo-anal anastomosis, SIAA) n = 29 o con reservorio en J (JIAA) n = 26 (55/72, 76%) fueron las reconstrucciones más habituales. Las complicaciones postoperatorias precoces que precisaron una intervención quirúrgica fueron muy poco frecuentes, pero se presentaron en 4/72 (5%) pacientes. Los síntomas a largo plazo relacionados con la función intestinal tras la reconstrucción, valorados en 57 niños mayores de cuatro años, fueron la dificultad para retener la defecación en 14 (25%), la encopresis en 21 (37%), las pérdidas fecales > 1/semana en 9 (16%) y el aumento de la frecuencia de defecación en 51 (89%). A largo plazo, se desarrolló una enterocolitis en 35/72 (47%) pacientes. Se precisó de nutrición enteral y/o parenteral suplementaria en algún momento del período de seguimiento en 51/93 (55%) pacientes. En los pacientes que respondieron a la encuesta entre 2 y 20 años (n = 56) de edad, se detectó un índice de masa corporal menor en 20 (35%) y una altura baja en 13 (23%) para su edad. En 35/57 (61%) pacientes mayores de 4 años con restauración del tránsito intestinal había restricciones sociales debido a los síntomas intestinales, de los que en 10 (17%) casos fueron moderadas o graves. CONCLUSIÓN: La reconstrucción de una TCA se asocia con síntomas intestinales persistentes y la enterocolitis sigue siendo frecuente. Un seguimiento multidisciplinario, incluso en la edad adulta, podría mejorar los resultados en la cirugía de la TCA.

Simultaneous HPLC determination of alfuzosin, tamsulosin and vardenafil in human plasma and pharmaceutical formulations using time programmed fluorescence detection.

Alfuzosin and tamsulosin are recently co-administrated with vardenafil to treat symptoms of benign prostatic hyperplasia and erectile dysfunction. A highly sensitive and simple liquid chromatographic method was developed and validated for the simultaneous determination of the three drugs using moxifloxacin as an internal standard. Isocratic separation was achieved within 7.0 min using phenyl-hexyl column (250 × 4.6 mm i.d.) and a mobile phase composed of acetonitrile/0.25% phosphoric acid (30:70, v/v) at pH 3.0. The analysis was performed at a flow rate of 1.2 mL/min with fluorescence detection at 246/450 nm for Alfuzosin and vardenafil, and 226/322nm for tamsulosin using time programming technique. The proposed method was linear over the concentration ranges of 5.0-50.0ng/mL, 10.0-200.0ng/mL and 20.0-400.0ng/mL for alfuzosin, vardenafil and tamsulosin, with limits of detection of 0.56ng/mL, 0.98ng/mL and 2.81 ng/mL in a respective order. The developed method was successfully applied to determine the studied drugs in dosage forms and human plasma samples and the results were satisfactory as revealed by statistical analysis of the data.

The somatotropic axis and longevity in mice.

The somatotropic signaling pathway has been implicated in aging and longevity studies in mice and other species. The physiology and lifespans of a variety of mutant mice, both spontaneous and genetically engineered, have contributed to our current understanding of the role of growth hormone and insulin-like growth factor I on aging-related processes. Several other mice discovered to live longer than their wild-type control counterparts also exhibit differences in growth factor levels; however, the complex nature of the phenotypic changes in these animals may also impact lifespan. The somatotropic axis impacts several pathways that dictate insulin sensitivity, nutrient sensing, mitochondrial function, and stress resistance as well as others that are thought to be involved in lifespan regulation.

Can natural levels of Al influence Cu speciation and toxicity to Daphnia magna in a Swedish soft water lake?

It is well known that chemical parameters, such as natural organic matter (NOM), cation content and pH may influence speciation and toxicity of metals in freshwaters. Advanced bioavailability models, e.g. Biotic Ligand Models (BLMs), can use these and other chemical parameters to calculate site specific recommendations for metals in the aquatic environment. However, since Al is not an input parameter in the BLM v.2.2.3, used in this study, there could be a discrepancy between calculated and measured results in Al rich waters. The aim of this study was to evaluate if the presence of Al in a circumneutral (pH ∼6) soft humic freshwater, Lake St. Envättern, will affect the Cu speciation and thereby the toxicity to the cladoceran Daphnia magna. The results show a statistically significant increase in the free Cu(2+) concentration with Al additions and that measured levels of Cu(2+) significantly differed from BLM calculated levels of Cu(2+). Furthermore, there was also a statistically significant elevated acute toxic response to D. magna at low additions of Al (10 µg/L). However, since the large difference between calculated and measured Cu(2+) resulted in a significant but minor (factor of 2.3) difference between calculated and measured toxicity, further studies should be conducted in Al rich soft waters to evaluate the importance of adding Al as an input parameter into the BLM software.

Evaluation of current copper bioavailability tools for soft freshwaters in Sweden.

The Water Framework Directive (WFD) in Europe calls for an improved aquatic ecological status. Biotic ligand models (BLM) have been suggested as a possible tool assisting in the regulatory process. The aim of this study was therefore to investigate the applicability of BLM under the WFD to set environmental quality standards (EQS), in particular regarding copper in Swedish freshwaters of which many are softer than those used for model calibration. Three different BLMs, one acute and two chronic, were applied to water chemistry data from 926 lakes and 51 rivers (1530 data entries) and evaluated with respect to their calibration range for input parameters. In addition, the predicted no-effect concentration (PNEC) for copper was calculated. From the 1530 data entries, 750 ended up outside of the BLM calibration range, when looking at the chemical parameters Ca(2+), alkalinity, pH and DOC, primarily due to low carbonate alkalinity. Furthermore, the calculated Cu PNECs were higher than the suggested Swedish limit for Cu (4µgL(-1)) in surface waters for 98% and 99% of the cases concerning lakes and rivers, respectively. To conclude, our findings show that water chemical characteristics outside of the calibration ranges are quite common in Sweden and that the investigated models differ in how they calculate toxicity concerning Cu under these conditions. As a consequence, additional work is required to validate the BLMs by use of bioassays with representative species of soft waters. Such results will show if these models can be used outside of their calibration ranges and also which of the models that gives the most reliable results.

Predictions of Cu toxicity in three aquatic species using bioavailability tools in four Swedish soft freshwaters.

BACKGROUND: The EU member countries are currently implementing the Water Framework Directive to promote better water quality and overview of their waters. The directive recommends the usage of bioavailability tools, such as biotic ligand models (BLM), for setting environmental quality standards (EQS) for metals. These models are mainly calibrated towards a water chemistry found in the south central parts of Europe. However, freshwater chemistry in Scandinavia often has higher levels of DOC (dissolved organic carbon), Fe and Al combined with low pH compared to the central parts of Europe. In this study, copper (Cu) toxicities derived by two different BLM software were compared to bioassay-derived toxicity for Pseudokirchneriella subcapitata, Daphnia magna and D. pulex in four Swedish soft water lakes. RESULTS: A significant under- and over prediction between measured and BLM calculated toxicity was found; for P. subcapitata in three of the four lakes and for the daphnids in two of the four lakes. The bioassay toxicity showed the strongest relationship with Fe concentrations and DOC. Furthermore, DOC was the best predictor of BLM results, manifested as positive relationships with calculated LC50 and NOEC for P. subcapitata and D. magna, respectively. CONCLUSION: Results from this study indicate that the two investigated BLM softwares have difficulties calculating Cu toxicity, foremost concerning the algae. The analyses made suggest that there are different chemical properties affecting the calculated toxicity as compared to the measured toxicity. We recommend that tests including Al, Fe and DOC properties as BLM input parameters should be conducted. This to observe if a better consensus between calculated and measured toxicity can be established.

Racing performance in Standardbred trotting horses with proximal palmar/plantar first phalangeal fragments relative to the timing of surgery.

REASONS FOR PERFORMING STUDY: Proximal palmar/plantar osteochondral fragmentation of the first phalanx is a frequent radiographic finding in Standardbred horses. These lesions are routinely removed prior to the onset of a racing career with no evidence to support the timing of this surgical intervention. OBJECTIVES: To determine whether horses racing before surgery slowed as they approached surgery date and whether they speeded up after surgery. To investigate the factors affecting whether a horse raced after surgery and compare the performance of horses that did and did not race before surgery. STUDY DESIGN: A retrospective study using 193 Swedish Standardbred trotters. METHODS: Medical records and radiographs of each horse were examined. Racing data were retrieved from official online records. Generalising estimating equations were used to examine presurgery racing performance and determine whether this differed between horses that raced before surgery and those that had not. Multivariable regression was used to examine career earnings and number of career races. RESULTS: Horses racing before surgery neither slowed as they approached surgery, nor speeded up after surgery. Race speed of horses raced before surgery was not different from those that only raced after surgery. Racing before surgery was not associated with whether horses raced following surgery. Only horses with 3 affected legs had slower race speeds than other horses. No other horse level variables affected race speed, number of career races, career earnings or top speed. CONCLUSIONS: There was no significant difference in race speed between horses that raced before surgery and those that did not. Horses did not slow down prior to surgery. Horses with 3 affected legs ran slower than those with only a single or 2 affected limbs. There was no association between timing of surgery and race speed or career longevity. The potential benefits of surgical intervention should be critically examined.

Serial transverse enteroplasty to facilitate enteral autonomy in selected children with short bowel syndrome.

BACKGROUND: Serial transverse enteroplasty (STEP) was first described in 2003 as a method for lengthening and tapering of the bowel in short bowel syndrome. The aim of this multicentre study was to review the outcome of a Swedish cohort of children who underwent STEP. METHODS: All children who had a STEP procedure at one of the four centres of paediatric surgery in Sweden between September 2005 and January 2013 were included in this observational cohort study. Demographic details, and data from the time of STEP and at follow-up were collected from the case records and analysed. RESULTS: Twelve patients had a total of 16 STEP procedures; four children underwent a second STEP. The first STEP was performed at a median age of 5·8 (range 0·9-19·0) months. There was no death at a median follow-up of 37·2 (range 3·0-87·5) months and no child had small bowel transplantation. Seven of the 12 children were weaned from parenteral nutrition at a median of 19·5 (range 2·3-42·9) months after STEP. CONCLUSION: STEP is a useful procedure for selected patients with short bowel syndrome and seems to facilitate weaning from parenteral nutrition. At mid-term follow-up a majority of the children had achieved enteral autonomy. The study is limited by the small sample size and lack of a control group.

An ecotoxicological evaluation of aged bottom ash for use in constructions.

Municipal and Industrial Solid Waste Incineration (MISWI) bottom ash is mainly deposited in landfills, but natural resources and energy could be saved if these ash materials would be used in geotechnical constructions. To enable such usage, knowledge is needed on their potential environmental impact. The aim of this study was to evaluate the ecotoxicity of leachates from MISWI bottom ash, aged for five years, in an environmental relevant way using a sequential batch leaching method at the Liquid/Solid-ratio interval 1-3, and to test the leachates in a (sub)chronic ecotoxicity test. Also, the leachates were characterized chemically and with the technique of diffusive gradients in thin films (DGTs). By comparing established ecotoxicity data for each element with chemically analysed and labile concentrations in the leachates, potentially problematic elements were identified by calculating Hazard Quotients (HQ). Overall, our results show that the ecotoxicity was in general low and decreased with increased leaching. A strong correspondence between calculated HQs and observed toxicity over the full L/S range was observed for K. However, K will likely not be problematic from a long-term environmental perspective when using the ash, since it is a naturally occurring essential macro element which is not classified as ecotoxic in the chemical legislation. Although Cu was measured in total concentrations close to where a toxic response is expected, even at L/S 3, the DGT-analysis showed that less than 50% was present in a labile fraction, indicating that Cu is complexed by organic ligands which reduce its bioavailability.

Roll to roll fabrication of thin film silicon solar cells on nano-textured substrates.

ECN is developing a novel fabrication process for thin film silicon solar cells on steel foil. Key features in this process are: (1) application of an insulating barrier layer which enables monolithic interconnection and texturization of the rear contact with submicron structures for light trapping; (2) Si deposition with remote, linear PECVD; (3) series interconnection by laser scribing and printing after deposition of all layers, which reduces the total number of process steps. The barrier layer is essential for the monolithic series interconnection of cells, but we show that it also enables optimum light trapping in the solar cells. We can fabricate any arbitrary sub-micron surface profile by hot embossing the barrier layer. For deposition of doped and intrinsic silicon layers we use novel remote, linear plasma sources, which are excellently suited for continuous roll-to-roll processing. We have been able to fabricate device-quality amorphous and microcrystalline silicon layers with these sources. The first nip a-Si cells were made on steel substrates with flat barrier layer and had initial efficiencies of 6.3%, showing the potential of the concept.

Ingestion of lead from ammunition and lead concentrations in white-tailed sea eagles (Haliaeetus albicilla) in Sweden.

In this study we show for the first time that lead poisoning from ammunition is a significant mortality factor for white-tailed sea eagle (WSE) (Haliaeetus albicilla) in Sweden. We analyzed 118 WSEs collected between 1981 and 2004 from which both liver and kidney samples could be taken. A total of 22% of all eagles examined had elevated (>6 microg/gd.w.) lead concentrations, indicating exposure to leaded ammunition, and 14% of the individuals had either liver or kidney lead concentrations diagnostic of lethal lead poisoning (>20 microg/gd.w.). Lead concentrations in liver and kidney were significantly correlated. In individuals with lead levels <6 microg/g, concentrations were significantly higher in kidney than in liver; in individuals with lead levels >20 microg/g, concentrations were significantly higher in liver. The lead isotope ratios indicate that the source of lead in individuals with lethal concentrations is different from that of individuals exhibiting background concentrations of lead (<6 microg/gd.w.) There were no significant sex or age differences in lead concentrations. A study from the Baltic reported in principle no biomagnification of lead, but background lead concentrations in WSE liver in this study were still four to >10 times higher than concentrations reported for Baltic fish from the same time period. In contrast to other biota there was no decrease in lead concentrations in WSE over the study period. The proportion of lead poisoned WSE remained unchanged over the study period, including two years after a partial ban of lead shot was enforced in 2002 for shallow wetlands. The use of lead in ammunition poses a threat to all raptors potentially feeding on shot game or offal. The removal of offal from shot game and alternatives to leaded ammunition needs to be implemented in order to prevent mortality from lead in raptors and scavengers.

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients.

AIMS/HYPOTHESIS: Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients. METHODS: In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. RESULTS: Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p = 9.4 x 10(-34); 45% vs 18%, p = 1.4 x 10(-16)), PTPN22 CT/TT (34% vs 26%, p = 0.0023; 31% vs 23%, p = 0.034), INS VNTR class I/I (69% vs 53%, p = 1.3 x 10(-8); 69% vs 51%, p = 8.5 x 10(-5)) and INS VNTR class IIIA/IIIA (75% vs 63%, p = 4.3 x 10(-6); 73% vs 60%, p = 0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p = 0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%). CONCLUSIONS/INTERPRETATION: Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.

Acute paediatric neck abscesses.

Acute neck swellings in a paediatric setting are often treated with antibiotics, proceeding to incision and drainage if an abscess is suspected. A variety of investigations are available and the causative organism can vary. A five-year retrospective study analysing trends in microbiology, antibiotic sensitivity, clinical evaluation and management of children presenting with an acute cervical abscess of four weeks duration or less was performed. The case notes of 175 children admitted between January 1996 and December 2000 to the acute surgical admission unit at the Royal Hospital of Sick Children, Glasgow were studied. During this period there were 90 males and 85 females with a mean age of three years (range: one month to 13 years). One hundred and twenty three (70%) children underwent surgery with pus being confirmed in 114 (93%) of cases. Ultrasound was performed in 70 (40%) patients with 48 proceeding to surgery. Positive culture of pus from abscess cavities revealed Staphylococcus aureus in 46% (85% sensitive to both flucloxacillin and erythromycin) and Streptococcus pyogenes in 15% (80% sensitive to penicillin and 75% to erythromycin). The role of investigations and the available treatment options are discussed.

Islet antibodies associated with pancreatic B-cell dysfunction at and 3 years after diagnosis of diabetes in subjects aged 35-64 years old: degree of impairment less severe than in those aged 0-34 years old.

AIMS: To determine differences in pancreatic B-cell function in relation to islet antibodies at diagnosis of diabetes and 3 years later in subjects aged 35-64 years old compared with those aged 0-34 years. METHODS: From a population-based diabetes register, 46 (0-34 years old) and 323 (35-64 years old) incident diabetic patients were investigated at diagnosis and 3 years later. Islet cell antibodies (ICA, GADA and IA-2A) and fasting plasma C-peptide were measured. RESULTS: Islet antibodies were found in 80% of the subjects aged 0-34 years and in 11% of those aged 35-64 years at diagnosis. ICA and GADA was the only combination of two islet antibodies detected in those aged 35-64 years and was, with or without IA-2A, associated with significantly lower median fasting C-peptide values than in those without or with only one antibody [0.35 nmol/l, interquartile range (IQR) 0.63 vs. 0.85 nmol/l, IQR 0.49; P = 0.0004]. However, fasting C-peptide in subjects aged 35-64 years old with multiple islet antibodies was higher than in those aged 0-34 years with islet antibodies (median 0 nmol/l, IQR 0.16, P = 0.0019). After 3 years' follow-up, fasting C-peptide was even lower in subjects aged 35-64 years old with three islet antibodies (median 0.14 nmol/l, IQR 0.27; P = 0.05). CONCLUSIONS: Islet antibodies were common in adults at diagnosis of diabetes. The combination of ICA and GADA indicates impaired B-cell function at diagnosis of diabetes in those aged 35-64 years old.

HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden.

AIMS/HYPOTHESIS: The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients. SUBJECTS AND METHODS: Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743. RESULTS: Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003). CONCLUSIONS/INTERPRETATION: Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes.

Longevity in mice: is stress resistance a common factor?

A positive relationship between stress resistance and longevity has been reported in a multitude of studies in organisms ranging from yeast to mice. Several mouse lines have been discovered or developed that exhibit extended longevities when compared with normal, wild-type mice of the same genetic background. These long-living lines include the Ames dwarf, Snell dwarf, growth hormone receptor knockout (Laron dwarf), IGF-1 receptor heterozygote, Little, alpha-MUPA knockout, p66(shc) knockout, FIRKO, mClk-1 heterozygote, thioredoxin transgenic, and most recently the Klotho transgenic mouse. These mice are described in terms of the reported extended lifespans and studies involving resistance to stress. In addition, caloric restriction (CR) and stress resistance are briefly addressed for comparison with genetically altered mice. Although many of the long-living mice have GH/IGF-1/insulin signaling-related alterations and enhanced stress resistance, there are some that exhibit life extension without an obvious link to this hormone pathway. Resistance to oxidative stress is by far the most common system studied in long-living mice, but there is evidence of enhancement of resistance in other systems as well. The differences in stress resistance between long-living mutant and normal mice result from complex interrelationships among pathways that appear to coordinate signals of growth and metabolism, and subsequently result in differences in lifespan.

Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes.

OBJECTIVE: To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. MATERIAL AND METHODS: Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. RESULTS: Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001). CONCLUSIONS: Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.

Glutathione metabolism in long-living Ames dwarf mice.

Ames dwarf mice live significantly longer than their wild type siblings and exhibit elevated antioxidative defenses and reduced oxidative damage. This study was conducted to determine the levels of components of glutathione (GSH) synthesis, degradation and utilization in dwarf and wild type mice. Glutamate-cysteine ligase protein levels were significantly elevated in dwarf liver at 3 and 24 months of age and muscle tissue at all ages examined. In kidney, activity of gamma-glutamyltranspeptidase (GGT) was decreased 42, 30 and 33% in 3, 12 and 24-month-old dwarf mice compared to wild type mice (P<0.0001). In contrast, GSH-S-transferase (GST) activity was markedly elevated (85, 113 and 53%) in kidneys of 3, 12 and 24-month-old dwarf mice (P<0.0001). GGT activity was higher in hearts of young dwarf and wild type mice while GST activity tended to be greater in dwarf mice. Similar to liver and kidney, brain GGT activity was also lower in dwarf mice (P<0.0001). Results of these experiments coupled with previous data provide a mechanism to partially explain the enhanced resistance to oxidative insult and conceivably, the extended longevity of dwarf mice.

Pre-tracheal air cyst.

Pre-tracheal air cysts or aeroceles are rare complications of tracheostomy. This is believed to be the first reported case in an adult presenting with a pre-tracheal air cyst 12 years after a tracheostomy. Only three case reports in children have been reported to date. The pathogenesis and treatment options are discussed and a method of managing this condition is suggested.