Effects of fat supplementation on glycaemic response and gastric emptying in adolescents with Type 1 diabetes

Aims To compare the glycaemic response to meals with different fat content in adolescents with Type 1 diabetes mellitus (T1DM) and to investigate associations with gastric emptying. Methods In this randomized, cross‐over study, paired results were obtained from seven adolescents with T1DM who ingested on different days two meals with the same carbohydrate and protein content, but different fat and energy content (2 and 38 g fat, 320 and 640 kcal, respectively). Paracetamol was mixed into the meals and gastric emptying was estimated by the paracetamol absorption method. All subjects were normoglycaemic and given 7 IU insulin aspart at commencement of ingestion. Postprandial blood samples were taken during 4 h. Results The areas under the curves for plasma glucose and serum paracetamol concentrations were larger after the low‐fat than after the high‐fat meal during the first 2 h (P = 0.047 and P = 0.041, respectively). The difference between meals in time‐to‐peak in glucose and paracetamol concentrations did not reach statistical significance (high‐fat vs. low‐fat meal: 210 min (120–240) vs. 120 min (50–240), P = 0.080 and 120 min (75–180) vs. 60 min (60–120), P = 0.051, respectively). Changes in glucose concentrations correlated with simultaneous changes in paracetamol concentrations (P < 0.001). Conclusions For the first time, we have shown that the initial glycaemic response is reduced after a meal with higher compared with a meal with lower fat content in adolescents with T1DM given a rapid‐acting insulin analogue preprandially. The type and dose of preprandial insulin may need adjustment to the fat content of the meal to reach postprandial normoglycaemia.     

Nuclear imaging of molecular processes in cancer

Molecular imaging using radionuclides has brought about the possibility to image a wide range of molecular processes using radiotracers injected into the body at very low concentrations that should not perturb the processes being studied. Examples include specific peptide receptor expression, angiogenesis, multi drug resistance, hypoxia, glucose metabolism, and many others. This article presents an overview, aimed at the non-specialist in imaging, of the radionuclide imaging technologies positron emission tomography and single photon radionuclide imaging, and some of the molecules labeled with gamma- and positron-emitting radioisotopes that have been, or are being, developed for research and clinical applications in cancer.     

Biological consequences of exposing ileal mucosa to urine

Segments of ileum are often used as conduits in connection with supravesicle diversion or sometimes for bladder augmentation. This implies that ileal mucosa will be deprived of the normal intestinal contents and instead exposed to urine. Reports on the morphological consequences of exposure to urine have been contradictory. Either normal structure or various degrees of atrophy have been reported. For this reason, an investigation was designed for systematic follow-up of effects on the ileal mucosa in patients with continent ileal reservoirs for urinary collection (Kock pouch). These investigations showed that there were significant changes in villous height, crypt depth, and number of goblet cells starting early after construction and leading to complete atrophy in certain areas. Electron microscopy and enzyme histochemistry also showed, in the epithelial cells, that there was a reduction in the number of cell organelles and microvillous units, and also decreased metabolic activity. Reductions were also recorded in studies of net transport of both water and electrolytes across the mucosa of the ileal reservoir used for urinary collection.From the clinical point of view, the adaptive changes recorded in the investigations of ileal mucosa exposed to urine are advantageous, since the risk of metabolic disturbances due to reabsorption of urine is diminished.

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Resumen Segmentos de íleo son frecuentemente utilizados como canal urinario en casos de desviación supravesical o, algunas veces, para agrandamiento de le vejiga. Esto quiere decir que la mucosa ileal, en vez de recibir el contenido intestinal normal, queda expuesta a la orina. Los informes sobre las consecuencias morfológicas de la exposición a la orina han sido contradictorios; se ha informado tanto la presencia de una estructura normal como de atrofia. Por tal razón se diseñó una investigación para el seguimiento sistemático de los efectos sobre la mucosa ileal en pacientes con reservorios urinarios ileales continentes (bolsa de Kock). La investigación demostró que se presentan cambios de significación en cuanto a altura de las vellosidades, profundidad de las criptas, y número de células caliceales, comenzando muy temprano después de la creación de la bolsa y dando lugar a atrofia completa en ciertas áreas. La microscopía electrónica y la histoquímica enzimática también demostraron que en las células epiteliales había reducción en el número de los organelos, las unidades microvellosas, y una reducida actividad metabólica. También se registraron reducciones en los estudios de transporte neto tanto de agua como de electrolitos a través de la mucosa del reservorio ileal utilizado para la recolección de la orina.Desde el punto de vista clínico, los cambios de adaptación registrados en la investigación realizada sobre la mucosa ileal expuesta a orina son ventajosos, puesto que disminuyen el riesgo de alteraciones metabólicas producidas por la reabsorción de la orina.

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Résumé Des segments de l'iléon sont souvent employés pour augmenter la capacité de la vessie ou pour la remplacer. Ce fait implique que la muqueuse iléale exempte du contenu intestinal normal est exposée à l'action de l'urine. Des études sur les conséquences morphologiques dues à ce facteur ont abouti à des résultats contradictoires. Tantôt la structure a été considérée comme normale, tantôt des degrés divers d'atrophie ont été constatés. Pour cette raison une étude a été entreprise pour établir les effets secondaires de l'urine sur la muqueuse de l'iléon, en particulier après la constitution d'une néo-vessie selon la technique de Kock. Cette étude a montré des modifications significatives de la hauteur des villosités, de la profondeur des cryptes, du nombre des cellules à gobelet, modifications débutant rapidement après la confection du réservoir iléal et aboutissent à une atrophie complète en certaines zones. La microscopie électronique et l'histochimie enzymatique ont montré qu'au niveau des cellules épithéliales se manifestent aussi une réduction du nombre des organelles cellulaires, des unités microvilleuses, et de l'activité métabolique. Une réduction du transport à la fois de l'eau et des électrolytes au travers de la muqueuse iléale du réservoir a été également constatée.D'un point de vue clinique, les phénomènes d'adaptation constatées au niveau de la muqueuse iléale soumise au contact de l'urine ont pour avantage de réduire les risques d'altérations métaboliques dues à la réabsorption de l'urine.

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Supported by grants from the Swedish Medical Research Council (no. 00577).     

Estimated glomerular filtration rate in stable older kidney transplant recipients—are present algorithms valid? A national cross‐sectional cohort study

Several equations have been developed for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD), but none were developed based on data from elderly kidney transplant recipients (KTR). The primary aim of this study was to evaluate different creatinine‐based equations in stable elderly KTR. A national cross‐sectional study was performed using data from 263 consecutive kidney transplant recipients 60 years or older who performed a routine GFR measurement one year after engraftment. GFR was measured by iohexol clearance calculation based on two samples. eGFR was calculated from a range of different creatinine‐based equations using information obtained at the time of GFR measurement. Bias, precision, and accuracy were evaluated for each equation. All equations apart from Nankivell had accuracy (P30) > 80%. The BIS1, FAS, LMR_CR, and Cockcroft & Gault equations in recipients older than 70 years and the FAS, LMR_CR, and MDRD in recipients 60–69 years old had nonsignificant bias. The CKD‐EPI had significant bias in both groups. If one should choose a single equation for follow‐up of individual CKD progression in all recipients ≥ 60 years, the FAS or LMR_CR equations are probably the best alternatives.     

Kidney allograft subclinical rejection modulates systemic inflammation measured by C‐reactive protein at 1 year after transplantation

Kidney allograft inflammation is associated with proinflammatory modifications of peripheral blood mononuclear cells, suggesting that renal inflammation contributes to systemic inflammation. Thus, the aim of this study was to evaluate the relationship between subclinical inflammation in surveillance biopsies performed at 1 year and systemic inflammation assessed by C‐reactive protein (CRP) levels at the time of biopsy. We analyzed 544 surveillance biopsies performed at 1 year that were classified as normal (n = 368), borderline (n = 148), or subclinical rejection (SCR) (n = 28). CRP levels were divided into quartiles. Patients in 1st, 2nd, and 3rd quartile were classified as low CRP (n = 408) and patients in the 4th quartile as high CRP (n = 136). Univariate analysis showed that the proportion of patients with SCR was higher in the high CRP group (10.3% vs 3.4%, P = 0.0067). Multivariate analysis showed that independent predictors of high CRP were body mass index (odds ratio [OR] 1.072 and 95% confidence interval [CI] 1.027‐1.119), a positive urine culture at the day of the biopsy (OR 2.760 and 95% CI 1.205‐6.323), and the presence of SCR at 1‐year surveillance biopsy (OR 7.260 and 95% CI 3.530‐14.935). In summary, we describe that subclinical acute rejection constitutes an independent predictor of systemic inflammation as measured by CRP.     

A before‐and‐after observational study of a protocol for use of the C‐MAC videolaryngoscope with a Frova introducer in pre‐hospital rapid sequence intubation

Results using videolaryngoscopy in pre‐hospital rapid sequence intubation are mixed. A bougie is not commonly used with videolaryngoscopy. We hypothesised that using videolaryngoscopy and a bougie as core elements of a standardised protocol that includes a drugs and a laryngoscopy algorithm would result in a high first‐pass tracheal intubation success rate. We employed videolaryngoscopy (C‐MAC) combined with a bougie (Frova intubating introducer) in an anaesthetist‐staffed helicopter emergency medical service. Data for adult tracheal intubation were collected prospectively as part of the airway registry of our unit for 22 months after implementation of the protocol (n = 543) and compared with controls (n = 238) treated in the previous year before the implementation. The mean first‐pass success rate (95%CI) was 98.2% (96.6–99.0%) in the study group and 85.7% (80.7–89.6%) in the control group, p < 0.0001. Combining C‐MAC videolaryngoscopy and bougie with a standardised rapid sequence induction protocol leads to a high first attempt intubation success rate when performed by an anaesthetist‐led helicopter emergency medical service team.     

Interaction among smoking status,single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking‐related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty‐four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never‐users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C‐reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8^dim cells in the lymphocyte group, CD13⁺ CD11⁺, CD13⁺ CD14⁺, CD13⁺ CD56⁺ cells in the monocyte group and CD13⁺ CD11⁺, CD13⁺ CD56⁺ cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8⁺ GZB⁺ cells in the CD8^dim group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking‐related disease and the variations observed in clinical outcomes.