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.     

Bariatric surgery reduces fasting total fatty acids and increases n-3 polyunsaturated fatty acids in morbidly obese individuals

Background: Obesity is a global pandemic leading to increased mortality and increased risk of cardiovascular disease. Bariatric surgery is an established treatment of obesity leading to weight loss and reduction of mortality. To further elucidate how bariatric surgery improves metabolic control, we explored the fatty acid (FA) profiles in morbidly obese subjects treated with lifestyle intervention and subsequent bariatric surgery.

Methods: The intervention group consisted of 34 morbidly obese patients scheduled for bariatric surgery and the control group of 17 non-obese patients scheduled for elective laparoscopic procedures. The intervention group had to undergo lifestyle changes preoperatively. Fasting blood samples were drawn at admission, after lifestyle intervention and 1 year after bariatric surgery.

Results: At admission, the morbidly obese patients had significantly higher levels of monounsaturated FAs (MUFAs) and lower levels of n-6 polyunsaturated FAs (PUFAs) and n-3 PUFAs than healthy controls (all p-values <.05). In the intervention group, there was a significantly lower level of total FAs after lifestyle intervention, and from admission to 1 year after surgical intervention (both, p?<?.05), primarily reflecting a lower proportion of saturated FAs (SFAs). Following bariatric surgery, but not after lifestyle changes, there was an increase in the proportion of n-3 PUFA (p?<?.05) reaching levels not significantly different from healthy controls.

Conclusions: Our findings suggest that a reduced proportion of the proposed anti-atherogenic n-3 PUFAs characterizes morbidly obese individuals, and that this FA profile is reversed by bariatric surgery, but not by lifestyle intervention.     

KAMEDO report no. 85: collapse of building during wedding reception in Jerusalem, 2001

What is now known as the "Versailles Disaster" began as a wedding celebration in Jerusalem on 24 May 2001. The reception was held in the third floor banqueting hall of a hotel, the floor of which subsequently collapsed, crashing through the second and first floors of the building. Four hundred people fell with the floor, and 310 injured people were evacuated using the scoop-and-run principle. The total number of dead was 23, which was less than might have been expected. Israel's on-site disaster management system of giving control to the first paramedic on the scene appeared to work well; however, the other emergency services did not act in coordination with the paramedics. The hospitals managed patients efficiently and social workers were mobilized quickly to assist people experiencing psychological trauma.     

Determination of CYP2D6 gene copy number by pyrosequencing

BACKGROUND: Identification of CYP2D6 alleles *5 (deletion of the whole CYP2D6 gene) and *2xN (gene duplication) is very important because they are associated with decreased or increased metabolism of many drugs. The most commonly used method for analysis of these alleles is, however, considered to be laborious and unreliable. METHODS: We developed a method to determine the copy number of the CYP2D6*5 and CYP2D6*2xN alleles by use of Pyrosequencing technology. A single set of PCR and sequencing primers was used to coamplify and sequence a region in the CYP2D6 gene and the equivalent region in the CYP2D8P pseudogene, and relative quantification between these fragments was performed. The CYP2D8P-specific Pyrosequencing peak heights were used as references for the CYP2D6-specific peak heights. RESULTS: Analysis of 200 pregenotyped samples showed that this approach reliably resolved 0-4 genome copies of the CYP2D6 gene. In 15 of these samples, the peak pattern from one analyzed position was unexpected but could be solved by conclusive results from a second position. The method was verified on 270 other samples, of which 267 gave results that corresponded to the expected genotype. One of the samples could not be interpreted. The reproducibility of the method was high. CONCLUSIONS: CYP2D6 gene copy determination by Pyrosequencing is a reliable and rapid alternative to other methods. The use of an internal CYP2D8P control as well as generation of a sequence context ensures a robust method and hence facilitates method validation.     

Impact of age on risk of complications after gastric bypass: A cohort study from the Scandinavian Obesity Surgery Registry (SOReg)

Background

An increasing number of older patients undergo bariatric surgery.

Twice-daily biphasic insulin aspart 30 versus biphasic human insulin 30: a double-blind crossover study in adults with type 2 diabetes mellitus

OBJECTIVE: The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart (BIAsp 30) with the equivalent premixed biphasic human insulin (BHI 30), administered twice daily, in patients with type 2 diabetes mellitus. METHODS: In this randomized, double-blind, crossover trial, 13 patients (mean age, 64 years; baseline mean glycosylated hemoglobin, 7.7%; mean body mass index, 28.1 kg/m2) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast. At the end of each 2-week treatment period, 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays. All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance. RESULTS: Total daily insulin exposure was similar between treatment periods. Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17% greater than that of BHI 30 after dinner and 44% greater after breakfast; both differences were statistically significant. The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner (18%) and breakfast (35%). Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group; differences were significant only after breakfast. The mean daily prandial glucose excursion was significantly lower for BIAsp 30 (16.2 mmol x h x L(-1)) than BHI 30 (17.9 mmol x h x L(-1)). Postprandial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast, but were significantly greater after lunch. Mean 24-hour and nocturnal serum glucose concentrations were similar, and both insulins were associated with < or = 7 minor and no major hypoglycemic events. CONCLUSIONS: Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postprandial glucose excursions. This effect may be of importance when improvement in postprandial glucose control is desired.     

Weight loss,adverse events,and loss to follow-up after gastric bypass in young versus older adults: A Scandinavian Obesity Surgery Registry study

Background

Young adults display particularly poor weight loss in behavioral obesity treatment; nonetheless, they have seldom been included in bariatric research.

N400-like magnetoencephalography responses modulated by semantic context,word frequency,and lexical class in sentences

Words have been found to elicit a negative potential at the scalp peaking at approximately 400 ms that is strongly modulated by semantic context. The current study used whole-head magnetoencephalography (MEG) as male subjects read sentences ending with semantically congruous or incongruous words. Compared with congruous words, sentence-terminal incongruous words consistently evoked a large magnetic field over the left hemisphere, peaking at approximately 450 ms. Source modeling at this latency with conventional equivalent current dipoles (ECDs) placed the N400 m generator in or near the left superior temporal sulcus. A distributed solution constrained to the cortical surface suggested a sequence of differential activation, beginning in Wernicke's area at approximately 250 ms, spreading to anterior temporal sites at approximately 270 ms, to Broca's area by approximately 300 ms, to dorsolateral prefrontal cortices by approximately 320 ms, and to anterior orbital and frontopolar cortices by approximately 370 ms. Differential activity was exclusively left-sided until >370 ms, and then involved right anterior temporal and orbital cortices. At the peak of the N400 m, activation in the left hemisphere was estimated to be widespread in the anterior temporal, perisylvian, orbital, frontopolar, and dorsolateral prefrontal cortices. In the right hemisphere, the orbital, as well as, weakly, the right anterior temporal cortices were activated. Similar but weaker field patterns were evoked by intermediate words in the sentences, especially to low-frequency words occurring in early sentence positions where there is little preceding context. The locations of the N400 m sources identified with the distributed solution correspond well with those previously demonstrated with direct intracranial recordings, and suggested by functional magnetic resonance imaging (fMRI). These results help identify a distributed cortical network that supports online semantic processing.     

Variations in assay protocol for the Dako cystatin C method may change patient results by 50% without changing the results for controls.

BACKGROUND: Cystatin C is increasingly used as a glomerular filtration marker, but so far only a few companies produce most of the cystatin C reagents suited for turbidimetry or nephelometry use in clinical laboratories. METHODS: We studied different protocols for measuring cystatin C on an Architect ci8200 system using cystatin C reagents from Dako (Glostrup, Denmark). The results were compared with those obtained with Dade Behring reagents (Deerfield, IL, USA) on a BN ProSpec system. RESULTS: Differences in assay protocol on the same instrument with the Dako reagent yielded an up to 50% difference in glomerular filtration rate calculated from the cystatin C results when analyzing patient samples, but had no effect on the results for controls. There were also significant differences regarding linearity and kinetics between samples and controls/calibrators. CONCLUSIONS: The results indicate different reactivity of the Dako antibodies against calibrators and controls in comparison with patient samples, highlighting the importance of using controls and calibrators that do not differ from patient samples.