Development and validation of a minimally invasive and image-guided tape stripping method to sample atopic skin in children.

BACKGROUND: Molecular skin profiling techniques, typically performed on skin samples taken by punch biopsy, have enhanced the understanding of the pathophysiology of atopic dermatitis (AD), thereby enabling the development of novel targeted therapeutics. However, punch biopsies are not always feasible or desirable, and novel minimally invasive methods such as skin tape stripping have been developed. AIM: To develop, optimize and validate a novel tape stripping method guided by noninvasive in vivo skin imaging to sample atopic skin in children. METHODS: Skin tape stripping-based procedures were compared and optimized using data from 30 healthy controls (HCs: 5 adults, 25 children) and 39 atopic children. Evaluations were guided by high-resolution photography, reflectance confocal microscopy, optical coherence tomography and transepidermal water loss measurements. We assessed and compared adverse events (AEs), the time needed to perform the sampling and the cDNA levels obtained from the tapes. RESULTS: Tape stripping methods based on previously described protocols resulted in erosions in all participants and required a median time of 65 min to perform (range 60-70 min), but provided good cDNA yield. Shorter durations appeared less invasive but provided lower cDNA yield. The final optimized tape stripping protocol, using 11 tapes of 22 mm in diameter, each applied twice for 5 s with 90° rotation, did not produce significant AEs, was completed within a median time of 7 min (range 5-15 min) and provided good cDNA yield both in HCs and atopic children. CONCLUSION: Our minimally invasive method is safe and reliable, and provides reproducible acquisition of cDNA in atopic children. In addition, it enables rapid sample collection, a crucial factor in clinical practice.

Monocyte secretory profiling in a clinical and MEFV genotype-characterized cohort of Danish familial Mediterranean fever patients: diagnostic potential of CCL1 and CXCL1.

OBJECTIVE: The autoinflammatory disease familial Mediterranean fever (FMF), characterized by recurrent attacks of sterile fever, serosal, and/or synovial inflammation, is caused by variants in the Mediterranean fever gene, MEFV, coding for the pyrin inflammasome sensor. The diagnosis of FMF is mainly based on clinical symptoms and confirmed by detection of disease-associated MEFV variants. However, the diagnosis is challenging among patients carrying variants of uncertain clinical significance (VUS). In this study, we aimed to identify potential FMF discriminatory diagnostic markers in a cohort of clinically characterized FMF patients. METHOD: We established a cohort of clinically and MEFV genotype-characterized FMF patients by enrolling patients from major Danish hospitals (n = 91). The secretory profile of pyrin inflammasome-activated monocytes from healthy donors (HDs) and MEFV-characterized FMF patients (n = 28) was assessed by analysing cell supernatants for a custom-designed panel of 23 cytokines, chemokines, and soluble tumour necrosis factor receptors associated with monocyte and macrophage function. RESULTS: MEFV genotypes in Danish FMF patients were associated with age at symptom onset (p < 0.05), FMF among relatives (p < 0.01), proportion of patients in colchicine treatment (p < 0.01), and treatment response (p < 0.05). Secretion of chemokines CCL1 and CXCL1 from pyrin-activated FMF monocytes was significantly decreased compared to HDs (p < 0.05), and could discriminate FMF patients with 'non-confirmatory' MEFV genotypes from HDs with 80.0% and 70.0% sensitivity for CCL1 and CXCL1, respectively (p < 0.05). CONCLUSION: Our data suggest that a functional diagnostic assay based on CCL1 or CXCL1 levels in pyrin-activated patient monocytes may contribute to FMF diagnosis in patients with VUS.

Swine diets: Impact of carbohydrate sources on manure characteristics and gas emissions.

Swine growers seeking to lower costs and environmental impact have turned to alternative carbohydrate feed sources. A feeding trial was conducted to determine the effect carbohydrate sources have on manure composition and gas emissions. A total of 48 gilts averaging 138 kg BW were fed diets consisting of (a) low fiber (LF) grain, or (b) high fiber (HF) aro-industrial co-product (AICP). The LF diets included corn and soybean meal (CSBM) and barley soybean meal (BSBM). The HF AICP diets were CSBM based and supplemented with one of the following materials: beet pulp; corn distillers dried grains with solubles; soybean hulls; or wheat bran. Diets were fed for 42 d with an average daily feed intake of 2.71 kg d-1. Feces and urine were collected twice daily and added to manure storage containers in which manure slurries were monitored for gas emissions and chemical properties. Manures of animals fed HF diets had significantly (P < 0.05) more excretion of solids, C, N, and organic N, but less total S compared to pigs fed the LF diets. Animals feed HF diets had significantly (P < 0.05) higher levels of ammonia, sulfide, volatile fatty acids, and phenols in manure compared to pigs fed the LF diets. Manure of animals fed HF diets had 30% (P < 0.05) lower NH3 and 17% lower hydrogen sulfide emissions; however, fiber had no impact on odor emissions. Based on the partitioning of nutrients, animals fed HF fiber diets had increased manure retention for C and N but decreased levels of N gas emissions and manure S. There were little differences in manure and gas emissions for animals fed LF diets, but the source of HF AICP diets had a significant impact on manure composition and gas emissions.

Swine diets impact manure characteristics and gas emissions: Part I protein level.

Crude protein (CP) is a key nutrient in swine diets supplying essential amino acids, N, and S to animals for growth are fed in excess to maximize growth. Swine diets reduced in CP and supplemented with crystalline amino acids have been shown effective at maintaining animal growth while increasing overall CP use efficiency. A feeding trial study was conducted to determine the effects of reduced dietary CP levels on manure slurry chemical properties and gas emissions. A total of 24 gilts averaging 111 kg BW were fed corn and soybean meal diets formulated with 8.7, 14.8, and 17.6% CP using crystalline amino acid supplementation in the 8.7 and 14.8% CP diets, but only intact protein, soybean meal, in the diet containing 17.6% CP. Diets were fed for 45 d with an average daily feed intake (ADFI) of 2.70 kg across all diets. Animals were fed twice daily with both feces and urine collected during each feeding and added to animal-specific manure storage containers. At the end of the study, manure slurries were monitored for gas emissions and chemical properties. Increasing dietary CP levels increased manure pH, total solids, total N, and total S, including increased levels of ammonia (NH3), volatile fatty acids, and phenolic compounds. Pigs fed lower CP diets had lower emissions of NH3, branched chain fatty acids (BCFA), and phenol compounds which translated into lower emissions in total odor. Emissions of NH3 and odor were reduced by 8.9% and 4.2%, respectively, for each unit percent decline in dietary CP. Hydrogen sulfide was the dominate odorant associated with manure odor emissions. Based on nutrient mass balance, animal retention of dietary N and S increased by 7.0% and 2.4%, respectively, for each unit percent drop in crude protein fed animals, while C retention in the animal declined by 2.1%.

Swine diets impact manure characteristics and gas emissions: Part II protein source.

Soybean meal is the dominate protein source for swine diets in the world driven largely by economics, nutritive value, and availability; but conditions can change requiring growers to consider more economical and available protein alternatives. A feeding trial was conducted to determine the impact dietary protein source material on manure slurry chemical properties and manure gas emissions. A total of 32 gilts averaging 130 kg BW were fed either a control diet formulated with soybean meal (SB) or an alternative protein source that included corn gluten meal (CG); canola meal (CM); or poultry meal (PM), with all diets containing 176 g protein kg-1. Diets were fed for 45 d with an average daily feed intake of 2.68 kg/d. Feces and urine were collected twice daily after each feeding and added to animal-specific manure storage containers. At the end of the study, manure slurries were monitored for gas emissions and chemical properties. Dietary protein source had a significant effect (P < 0.05) on manure pH, total solids, total C, protein N, and total S. Pigs fed the diets containing CM had significantly higher levels of sulfide, butanoic acid, and branch chain fatty acids compared to pigs fed SB diets (P < 0.05). Pigs fed CM diets had significantly lower emissions of NH3 compared to pigs fed SB diets (P < 0.05). There were no significant differences in C or S emissions or in odorant emission as affected by source of dietary protein. Hydrogen sulfide was the most dominate odorants for all dietary treatments.

Characteristics of patients with familial Mediterranean fever in Denmark: a retrospective nationwide register-based cohort study.

Objectives: To investigate epidemiology, demography, and genetic and clinical characteristics of patients with familial Mediterranean fever (FMF) in Denmark. Method: In this population-based, cross-sectional cohort study, we identified FMF patients from discharge diagnoses using ICD-10 codes in the Danish National Patient Register, and linked data from the Danish Civil Registration System and laboratory databases for results of MEFV gene variant screening. Results: We identified 495 FMF patients (prevalence 1:11 680) with a median age of 29 years and a female ratio of 51%. The median age at diagnosis of FMF was 13 (IQR 7-22) years, with an estimated median diagnostic delay of 3 (IQR 0.7-6.9) years. The predominant ethnicities were Turkish (41.8%), Lebanese (15.8%), Syrian (6.5%), South-West Asian (7.9%), and South-East Asian (3.0%). The MEFV genotype distribution was 18.7% homozygous, 21.2% compound heterozygous, 32.0% heterozygous, 11.0% with complex alleles or unresolved zygosity, and 17.1% with no detected variants. M694V was the most prevalent variant in the overall cohort (32.5%). Homozygous or compound heterozygous MEFV exon 10 variants were associated with younger age at diagnosis (p < 0.001) and reduced number of hospital contacts before diagnosis (p = 0.008). The Charlson Comorbidity Index was ≥ 2 in 8.1% of patients. The prevalence of amyloidosis was 1.0%. Conclusions: FMF in Denmark is rare and patients are mainly of Eastern Mediterranean ethnicity. Diagnostic delay was long but patients with exon 10 MEFV variants were diagnosed at a younger age. Prolonged diagnostic delay is probably caused by lack of FMF awareness in the Danish healthcare system.

Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared late complication. Treatment options are lacking at present. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with adipose-derived regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up. MATERIAL AND METHODS: We included 10 patients with BCRL. ADRCs were injected directly into the axillary region together with a scar-releasing fat grafting procedure. Primary endpoint was change in arm volume. Secondary endpoints were change in patient-reported outcomes, changes in lymph flow, and safety. RESULTS: During follow-up, no significant change in volume was noted. Patient-reported outcomes improved significantly with time. Five patients reduced their use of conservative management. Quantitative lymphoscintigraphy did not improve on the lymphedema-affected arms. ADRCs were well tolerated, and only minor transient adverse events related to liposuction were noted. CONCLUSIONS: In this pilot study, a single injection of ADRCs improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events during the follow-up period. Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There was no change in excess arm volume. Results of this trial need to be confirmed in randomized clinical trials.

Local overexpression of the myostatin propeptide increases glucose transporter expression and enhances skeletal muscle glucose disposal.

Insulin resistance (IR) in skeletal muscle is a prerequisite for type 2 diabetes and is often associated with obesity. IR also develops alongside muscle atrophy in older individuals in sarcopenic obesity. The molecular defects that underpin this syndrome are not well characterized, and there is no licensed treatment. Deletion of the transforming growth factor-ß family member myostatin, or sequestration of the active peptide by overexpression of the myostatin propeptide/latency-associated peptide (ProMyo) results in both muscle hypertrophy and reduced obesity and IR. We aimed to establish whether local myostatin inhibition would have a paracrine/autocrine effect to enhance glucose disposal beyond that simply generated by increased muscle mass, and the mechanisms involved. We directly injected adeno-associated virus expressing ProMyo in right tibialis cranialis/extensor digitorum longus muscles of rats and saline in left muscles and compared the effects after 17 days. Both test muscles were increased in size (by 7 and 11%) and showed increased radiolabeled 2-deoxyglucose uptake (26 and 47%) and glycogen storage (28 and 41%) per unit mass during an intraperitoneal glucose tolerance test. This was likely mediated through increased membrane protein levels of GLUT1 (19% higher) and GLUT4 (63% higher). Interestingly, phosphorylation of phosphoinositol 3-kinase signaling intermediates and AMP-activated kinase was slightly decreased, possibly because of reduced expression of insulin-like growth factor-I in these muscles. Thus, myostatin inhibition has direct effects to enhance glucose disposal in muscle beyond that expected of hypertrophy alone, and this approach may offer potential for the therapy of IR syndromes.

Analysis of errors in laparoscopic surgical procedures.

BACKGROUND: The determination of laparoscopic surgeon ability is essential to training error avoidance. The present study describes a practical method of surgical error analysis. METHODS: After review of practice videotapes of the excisional phase of laparoscopic cholecystectomy, consensus on the identification of eight errors was achieved. Interrater agreement at the end of this phase was 84-96%. Fourteen study videotapes of gallbladder excision were then observed independently by expert reviewers blinded to surgical team identity. Procedures were assessed using a scoring matrix of 1-min segments with each error reported each minute. RESULTS: Interrater agreement was 84-100% for all error categories. CONCLUSIONS: The present study demonstrates that excellent interrater agreement of procedural errors can be achieved by carefully defining and training recognition of targeted events. Extension of this simple and reliable analysis tool to other procedures should be feasible to define behaviors leading to adverse clinical outcomes.

Metabolic oscillations in an E. coli fermentation.

Recombinant E. coli fermentations were observed to undergo regular, reproducible oscillations in oxygen uptake for several hours during a controlled fermentation process. Culture growth slowed during the period of oscillations, delaying induction of recombinant protein production. The oscillations were similar in 10-L and 1,000-L fermentors and also occurred with different feed control algorithms. Both observations support the hypothesis that the oscillations are metabolic in nature. Analysis of amino acid, ATP, and GTP pools suggests that the oscillations result from aberrant regulation of isoleucine biosynthesis leading to repeated starvation events in which protein synthesis and growth are impaired. Both a nutritional solution, isoleucine feeding, and a genetic solution, repair of an ilvG frameshift mutation in E. coli K-12 strains, were found to eliminate the oscillations, further supporting the proposed mechanism for the behavior. These results illustrate the interesting and complicated physiological behavior which can be displayed in metabolic networks and provide another example of surprising problems that can arise in growing recombinant organisms in fermentors.

Pancreatic resection: effects on glucose metabolism.

Pancreatic resection results in hormonal abnormalities that are dependent on the extent and location (proximal versus distal) of the resected portion of the gland. The form of glucose intolerance which results from pancreatic resection is termed pancreatogenic diabetes. It is associated with features distinct from both type I (insulin-dependent) and type II (insulin-independent, or adult-onset) diabetes. Hepatic insulin resistance with persistent endogenous glucose production and enhanced peripheral insulin sensitivity result in a brittle form of diabetes which can be difficult to manage. In addition to insulin deficiency, the endocrine abnormalities that accompany pancreatic resection can include glucagon deficiency or pancreatic polypeptide (PP) deficiency if the resection is distal or proximal, respectively. Glucagon deficiency can contribute to iatrogenic hypoglycemia, and PP deficiency can contribute to persistent hyperglycemia due to impaired hepatic insulin action. Pancreatic resections that spare the duodenum, such as distal pancreatectomy, duodenum-preserving pancreatic head resection (Beger procedure), or extended lateral pancreaticojejunostomy with excavation of the pancreatic head (Frey procedure), are associated with a lower incidence of new or worsened diabetes than the standard or pylorus-preserving pancreaticoduodenectomy (Whipple procedure) or total pancreatectomy. Operative considerations for the treatment of pancreatic disease should include strategies to minimize the hormonal impairment of pancreatic resection.

Laser resurfacing for dermal photoaging.

The skin is a highly organized system composed of resident cells, extracellular matrix, blood vessels, and circulating cells that all work together to maintain cutaneous integrity. Environmental insults, particularly sunlight, act to alter the skin permanently, producing visibly undesirable effects. By wounding the skin or inducing a healing response with minimal wounding, the repair process can be activated to return the skin to a more normal condition. Owing to the complexity of the healing response, even the most well-studied and precise laser system can result in unpredicted results when used to treat photo-damaged skin. Through continued research into the normal functioning of skin, the alterations brought about by chronic photodamage, and the repair process, an integrated approach to treatment of photoaging will evolve. Agents such as alpha-hydroxy acids, retinoids, and growth factors that impact the healing response can be combined with various lasers to optimize improvement of photo-damaged skin, while minimizing the adverse consequences of treatment.

Intestinal transplantation in pediatric patients: a nursing challenge. Part 2: Intestinal transplantation and the immediate postoperative period.

Intestinal transplantation offers new hope to children with intestinal failure and life-threatening complications of parenteral nutrition. As more transplant centers are adding intestinal transplantation to their existing programs, new challenges are presented to nursing professionals. This three-part series will provide information for nursing professionals regarding evaluation for intestinal transplantation, donor preparation, the surgical procedure, immediate postoperative care of the transplant recipient, and long-term care of the intestinal transplant recipient. This article focuses on donor selection and preparation, the surgical procedure for intestinal transplantation, the immediate postoperative course, immunosuppression, rejection, infections, fluid and electrolyte support, and nutrition. The information presented represents the approach taken at University of Nebraska Medical Center/Nebraska Health Systems.

Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity.

To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects before and after a hyperinsulinemic-euglycemic clamp following a five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. Rates of insulin stimulated whole-body glucose uptake. Glucose oxidation and muscle glycogen synthesis were 50%-60% lower following the lipid infusion compared with the glycerol infusion and were associated with a approximately 90% decrease in the increment in intramuscular glucose-6-phosphate concentration, implying diminished glucose transport or phosphorylation activity. To distinguish between these two possibilities, intracellular glucose concentration was measured and found to be significantly lower in the lipid infusion studies, implying that glucose transport is the rate-controlling step. Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1-associated PI 3-kinase activity.

Overexpression of hepatic pancreatic polypeptide receptors in chronic pancreatitis.

Pancreatic polypeptide (PP) receptors have recently been demonstrated on liver microsomal membranes although the mechanisms of PP action on hepatocytes remain uncertain. The binding characteristics of these high affinity receptors under pathophysiologic conditions were studied in rats with oleic acid-induced chronic pancreatitis (CP), a state associated with diminished pancreatic PP content. Sixteen pancreatitic and 11 sham-operated control animals either were 16-h fasted or were given free access to food prior to organ removal. Competitive binding studies were performed by incubating hepatocyte microsomal preparation with 125I-labeled PP (20-40 pM) and increasing concentrations of nonlabeled PP (1 x 10(-10) to 1 x 10(-6) M). After total and nonspecific binding was quantified by gamma counting, coefficients of dissociation (Kd) and maximal binding sites (Bmax) were determined by Scatchard analysis of specifically bound radioactivity. Binding data were normalized to membrane protein content and expressed as means +/- standard error. Bmax was significantly greater in tissue from fed control animals than from fasted controls (4.46 +/- 0.36 versus 2.83 +/- 0.25, P < 0.05). Bmax was significantly greater under fasted conditions in tissue from CP animals than from controls (5.25 +/- 0.94 versus 2.83 +/- 0.25, P < 0.01). Under fed conditions, this differences was abolished by the increase in maximal binding in the control group. The fasting-associated decrease in maximal binding sites observed in controls did not occur in CP specimens. Increased Bmax in fed versus fasted control, as well as fasted CP versus fasted control, were associated with slight reciprocal decreases in receptor affinity. These data indicate that hepatic PP receptor concentration is upregulated in this model of chronic pancreatitis, most likely due to diminished exposure to ligand. Furthermore, normal PP receptor responses to the fed/fasted state are blunted in this condition. Regulatable PP receptor changes may play a role in altered hepatic metabolism previously observed in chronic pancreatitis.

[Teratogenic effects of ACE-inhibitors and angiotensin II receptor antagonists]. / Fosterskadelige virkninger af ACE-haemmere og angiotensin II-receptorantagonister.

Since the introduction of angiotensin converting enzyme-inhibitors (ACE-inhibitors) in the 1980's, more than 50 cases of foetotoxic effects ascribed to intrauterine exposure to inhibitors have been published. Among the most commonly reported effects are: Hypotension, renal dysplasia, anuria/oliguria, oligohydramios, intrauterine growth retardation, pulmonary hypoplasia, unclosed ductus arteriosus, incomplete ossification of the skull, intrauterine og neonatal death. Recent animal studies have confirmed that intrauterine or neonatal exposure to ACE-inhibitors or the AT1-receptor antagonist losartan can cause death and serious, irreversible organ damage. These effects are similar to the complications previously reported in humans. Animal studies suggest that the foetotoxic actions are most common after exposure during the last trimester. However, due to the severity of these complications, the use of ACE-inhibitors and AT1-receptor antagonists should be avoided throughout pregnancy and in women who are breast feeding.

Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis.

Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic-euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol.m-2.min-1), HGP fell 91 +/- 5% in NL subjects but only 68 +/- 8% in CP subjects (P < 0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol.kg-1.min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 +/- 5%; CP: 86 +/- 15%) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (approximately -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.

Regulation of hepatic insulin receptors by pancreatic polypeptide in fasting and feeding.

Pancreatic polypeptide (PP) increases hepatic insulin receptor (IR) binding activity in fasted PP-deficient rats, but not fasted normal animals. PP-induced alteration of hepatic IR levels in normal animals may be detectable in the fed state when IR concentrations are lower than during fasting. In the current study, the effect of exogenous PP on IR concentrations in the fed and fasted states was determined in healthy 300- to 350-g male Sprague-Dawley rats. Ten animals were administered PP 100 microgram/kg/day for 3 days by intraperitoneal injection and 10 weight-matched control animals received saline vehicle. Five PP- and five saline-administered rats were fasted for 12 hr prior to organ procurement, while 5 PP- and 5 saline-treated rats were given free access to food for this period. Livers were removed and snap-frozen. IRs were isolated from solubilized hepatocyte membranes by affinity chromatography with agarose-bound wheat germ agglutinin. Western blots were performed using a specific antibody to the beta subunit of the IR, which was detected by a chemiluminescence technique after 45-min exposure to X-ray film. Exposed films were examined by scanning densitometry and IR concentration was expressed as absorbance units per milligram of hepatic protein (mean +/- SE). Statistical comparisons were by Student's t test with significance taken at P < 0.05. Feeding was associated with a significantly lower IR concentration in saline-administered animals compared with the fasted state (24.2 +/- 4.0 vs 53.3 +/- 11.1). PP administration in fed rats resulted in significantly increased IR concentration as compared with that seen in saline-administered fed animals (43.8 +/- 8.9 vs 24.2 +/- 4.0). This difference may be due to increased IR synthesis with long-term PP administration, and supports the role of PP as a regulatory factor in hepatic carbohydrate metabolism.

Classification of distal radius fractures: an analysis of interobserver reliability and intraobserver reproducibility.

The Frykman, Melone, Mayo, and AO classification systems for distal radius fractures were evaluated for interobserver reliability and intraobserver reproducibility in a clinical setting using initial plain radiographs. Two attending orthopedic hand surgeons and two attending radiologists classified 55 sets of distal radius fractures. kappa-statistics were used to establish a relative level of agreement between observers for the two readings and between separate readings by the same observer. Interobserver agreement was rated as moderate for the Mayo classification and fair for the Frykman, Melone, and AO classifications. Intraobserver agreement was substantial for only one of four observers for each of the Frykman, Melone, and Mayo, while the remaining three observers achieved only fair to moderate reproducibility. Intraobserver agreement for the AO classification was fair for all four of the observers. Neither interobserver or intraobserver agreement was affected by combining similar subclasses in the Melone classification or by reducing the number of categories in the AO system from 27 to 9. However, further reducing the AO system to its three main types brought agreement to the "substantial" level. No difference was found in interobserver agreement between the first and second readings or in interobserver or intraobserver agreement between orthopedic hand surgeons and radiologists. Understanding the limitations of fracture classifications based solely on plain radiographs can help avoid undue reliance on them. Given the low degree of interobserver and intraobserver agreement for each of the distal radius fracture classifications in this study, their use as the sole means for determining the direction of treatment or for the direct comparison of results among different studies is not warranted.