Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.     

Experience With Nocturnal Hemodialysis

In order to provide a highly efficient, long-duration form of hemodialysis, we developed nocturnal hemodialysis. Patients were dialyzed nightly at home for 8 – 10 hours, 6 – 7 nights/week. We kept the dialysate flow at 100 mL/min and the blood flow at 250 – 300 mL/min. Patients were monitored remotely from the hospital through a computer connection. An internal jugular line was used as an access. We have trained 12 patients over 30 months and have accumulated 160 patient-months worth of data. The patients tolerated the dialysis very well and slept through the night. There was a significant improvement in their sense of well-being. Nightly Kt/V was 0.99. Weekly removal of phosphate was two times as high and β ₂ -microglobulin four times as high as conventional hemodialysis. All patients have discontinued their phosphate binders and have increased their dietary phosphate and protein intake. Hypertension was controlled with fewer medications, and erythropoietin dosages decreased. Complications were infrequent and included catheter occlusion and infections. Reusing the dialyzers decreased the cost of the treatment to levels similar to continuous ambulatory peritoneal dialysis. Nocturnal hemodialysis represents a viable dialysis modality that combines high quality, low cost, and excellent tolerance.     

PROBLEM-SOLVING SUPPORT FOR TQM A Hypertext Approach

New IS technology is contributing to continuous quality improvement throughout the organization. Hypertext and hypermedia offer new ways for decision makers to gain easy and relevant access to information. By combining hypertext with total quality tools, decision makers are able to explore the richness of data bases in more creative and useful ways. This article describes how you can develop a hypertext system that can help employees improve their job performance through better problem solving.     

MULTI-PROJECT SCHEDULING WITH EXPLICIT LATENESS COSTS

We propose a heuristic procedure for planning and scheduling multiple projects subject to limited resource availabilities. We depart from previous research in that explicit lateness costs for each project are considered. Our procedure involves aggregate analysis using linear programming to determine target resource loading profiles for each project that optimize trade-offs of lateness costs among projects, followed by detailed multi-project scheduling consistent with the target profiles. Target profiles and detailed schedules are iteratively modified through N iterations, where N is the number of projects. The procedure can be used to jointly schedule previously committed and newly proposed projects, as well as to assign due dates to proposed projects. We compare the performance of our procedure to that of the traditional minimum slack heuristic, as well to a simple extension of the minimum slack rule that accounts for lateness costs. On a set of 60 multi-project test problems adapted from the Patterson set of single-project problems, results are very favorable for our proposed algorithm.     

The validity of the Gammarus:Asellus ratio as an index of organic pollution: abiotic and biotic influences.

In freshwaters. Gammarus spp. are more sensitive to organic pollution than Asellus spp. and the relative abundance of the two taxa has been proposed as a pollution index. We tested the validity of this by examining the relationship between the Gammarus: Asellus (G : A) ratio and (1) a suite of physico-chemical variables. (2) established biotic (average score per taxon, ASPT) and richness (species richness (S) and Ephemeroptera, Plecoptera and Trichoptera families richness (EPT family richness)) indices generated from the macroinvertebrate community. In addition, we investigated a suspected biotic interaction, predation, between Gammarus and Asellus. Both univariate and multivariate analyses showed that the G: A ratio was sometimes responsive to changes in parameters linked to organic pollution, such as BOD5 and nitrate levels. However, the G : A ratio also appeared responsive to variables not directly linked to organic pollution, such as conductivity and distance from source. There were significant positive correlations among the G : A ratio and the ASPT, S and EPT, indicating that changes in the relative abundances of Gammarus and Asellus were reflected in changes in the pollution sensitivity and richness of the wider macroinvertebrate community. A laboratory experiment revealed significant predation of Asellus aquaticus juveniles by Gammarus duebeni celticus adults, but no reciprocal predation. We propose that the G: A ratio may be useful as a crude measure of organic pollution that could supplement more complex indices in a multimetric approach to pollution monitoring or be used for monitoring individual sites, where a simple technique is required for monitoring purposes over a period of time. Also, we urge recognition of the possible role of biotic interactions among taxa used in the generation of pollution indices.     

Positional distribution of fatty acids in cardiolipin of mitochondria from 21-day-old rats

Pure cardiolipins (1,3-diphosphatidylglycerol) were prepared from mitochondria of heart, liver and kidney from 21-day-old male Wistar rats and submitted toNaja naja venom phospholipase A₂ (EC 3.1.1.4) action. Incubation conditions were controlled carefully, and a complete hydrolysis of cardiolipin to lysocardiolipin {di [1 (1″) acylsn-glycero-3-phosphoryl] 1′, 3′-sn-glycerol} and fatty acids from positions 2 (2″) was obtained in less than two hr practically without side reactions. Cardiolipins from the three organs contained low levels of saturated fatty acids; stearic acid accounted for 0.4–0.7% and palmitic acid for 1.4–3.5% of total fatty acids. These percentages apparently depended on the organ. In all three cases, linoleic acid was the major component, but its percentage varied from 62–78% of total fatty acids. Acyl chains linked to positions 1 (1″) of all three cardiolipin preparations exhibited a similar pattern; they were composed of linoleic acid for 85–89%. This fatty acid also was the main component esterified at position 2 (2″), but its percentage was much more variable: from 39.8% in heart to 51.2% in kidney and 67.8% in liver mitochondria. The remaining acids comprised octadecenoic and polyunsaturated fatty acids with more than 18 carbon atoms in different proportions. As opposed to other phospholipids,cis-vaccenic acid, and not oleic acid, was the main octadecenoic acid present in cardiolipins. Octadecenoic acids were nine- to 10-fold more concentrated at positions 2 (2″) than at positions 1 (1″). The percentage ofcis-vaccenic acid was four- to five-fold higher than that of oleic acid at positions 2 (2″), whereas oleic acid dominated at positions 1 (1″). From results presented in this study and selected literature data, it may be concluded that fatty acids are asymmetrically distributed in cardiolipins of different origins, with linoleic acid showing a definite preference for position 1 (1″).     

Opposed jet flames of lean or rich premixed propane-air reactants versus hot products

Several opposed jet flames, produced by a lean H₂-air jet opposing a rich or lean C₃H₈-air jet, are investigated. Spontaneous Raman spectroscopy is used for major species concentration and temperature measurements along the opposed jet centerline. The hot products of the H₂-air flame simulate the burnt gases of strong-burning near-stoichiometric reactants as they impinge upon a weak-burning lean or rich hydrocarbon-fueled reactant mix, a situation encountered in stratified charge operation of direct injection spark ignition engines. In addition the H₂-air flame hot products facilitate experimental data interpretation through the absence of carbon-bearing species. Good agreement between numerical and experimental data are obtained for a rich (equivalence ratio, φ = 1.25) C₃H₈-air jet versus a lean (φ = 0.4) H₂-air jet. Two lean C₃H₈-air jets (φ = 0.64 or 0.60), versus the φ = 0.4 H₂-air jet, are also investigated. For both of these flames, the amount of CO₂ production strongly depends upon φ, with the φ = 0.64 flame having a peak CO₂ mole fraction an order of magnitude higher than for the φ = 0.60 flame, and the C₃H₈ flames burning either as a normal flame (high CO₂) or as a “negative flame speed” flame producing little CO₂ and then only through diffusion of C₃H₈ into the hot products jet. The numerically predicted and experimental CO₂ profiles agree well for the positive flame speed flame, but the large discrepancy between predicted and measured peak CO₂ in the negative flame speed flame suggests modeling improvements are needed for this type of flame.