Gender-specific effects of capsiate supplementation on body weight and bone mineral density: a randomized, double-blind, placebo-controlled study in slightly overweight women.

INTRODUCTION: Overweight and obesity are highly prevalent conditions associated with premature morbidity and mortality worldwide. Capsiate, a nonpungent analogue of capsaicin, binds to TRP vanilloid 1 (TRPV1) receptor, which is involved in adipogenesis, and could be effective as a weight-lowering agent. METHODS: Eighteen slightly overweight women were enrolled in this randomized, double-blind, placebo-controlled study. Nine patients were included in the capsiate intervention group and received 9 mg/day of capsinoids and 9 patients received placebo for 8 weeks. All patients underwent weight and waist circumference assessment before and after treatment. Body composition and bone mineral density (BMD) were also detected by dual-energy X-ray absorptiometry (DXA). RESULTS: Fourteen patients completed the study. The treatment with capsiate or placebo for 8 weeks was not associated with significant changes in weight or waist circumference. After treatment, there was a significant improvement in BMD values measured at the spine in the capsiate group (1.158 vs 1.106 g/cm2, + 4.7%; p = 0.04), but not in the group treated with placebo. Similarly, the capsiate group showed a 9.1% increase (p = 0.05) in the adipose tissue and an 8.5% decrease in lean mass measured at the supraclavicular level, whereas these changes were not statistically significant in the placebo group. CONCLUSIONS: Treatment with capsiate for 8 weeks led to negligible changes in body weight in a small sample of slightly overweight women, but our findings suggest a potential effect of capsaicin on bone metabolism in humans.

The blue road: Provenance study of azurite samples from historical locations through the analysis of minor and trace elements.

The pigments used by artists since ancient times play an important role in historical, artistic, and cultural investigations. They allow the acquisition of useful information for the study of human and technological development. This research aims at differentiating the various sources of azurite exploited in antiquity, based on the study of minor and trace elements. Azurite is one of the most important blue pigments in art history, widely used during the Middle Age and Renaissance. However, very few studies investigated the provenance of the pigment, so today it is still not possible to clearly identify the sources of azurite exploited in the past. This study is based on the analysis of several samples of azurite belonging to the MUST collection (Museum of Earth Sciences, Sapienza University of Rome, Italy) and coming from different historical localities: UK, Italy, Germany, France, Romania and Slovakia (both representative of the resources within the ancient Kingdom of Hungary), Greece and Russia. The samples were analysed by electron microscopy (EMPA and SEM-EDX) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), with the aim of detecting chemical features that are specific to the different azurite ore deposits. Among the trace elements analysed, Zn, As, Sn, Ca and Sr prove the most suitable for discriminating the origin of the samples, as well as rare earth elements. In particular, Ce and Eu anomalies are suggested as markers for the German and Hungarian localities.

A Machine Learning-Based Approach to Clinopyroxene Thermobarometry: Model Optimization and Distribution for Use in Earth Sciences.

Thermobarometry is a fundamental tool to quantitatively interrogate magma plumbing systems and broaden our appreciation of volcanic processes. Developments in random forest-based machine learning lend themselves to a data-driven approach to clinopyroxene thermobarometry, allowing users to access large experimental data sets that can be tailored to individual applications in Earth Sciences. We present a methodological assessment of random forest thermobarometry using the R freeware package extraTrees. We investigate the model performance, the effect of hyperparameter tuning, and assess different methods for calculating uncertainties. Deviating from the default hyperparameters used in the extraTrees package results in little difference in overall model performance (<0.2 kbar and <3°C difference in standard error estimate, SEE). However, accuracy is greatly affected by how the final value from the distribution of trees in the random forest is selected (mean, median, or mode). Using the mean value leads to higher residuals between experimental and predicted P and T, whereas using median values produces smaller residuals. Additionally, this work provides two scripts for users to apply the methodology to natural data sets. The first script permits modification and filtering of the model calibration data set. The second script contains premade models, where users can rapidly input their data to recover PT estimates (SEE clinopyroxene-only model: 3.2 kbar, 72.5°C and liquid-clinopyroxene model: 2.7 kbar, 44.9°C). Additionally, the scripts allow the user to estimate the uncertainty for each analysis, which in some cases is significantly smaller than the reported SEE. These scripts are open source and can be accessed at https://github.com/corinjorgenson/RandomForest-cpx-thermobarometer.

Technological innovation of Continuous Glucose Monitoring (CGM) as a tool for commercial aviation pilots with insulin-treated diabetes and stakeholders/regulators: A new chance to improve the directives?

Civil aviation pilots who develop insulin-treated diabetes and want to renew a Commercial Pilot License (CPL) represent a medical, social and regulatory problem. This depends on justified concerns about hypoglycemia, the most threatening event for people who carry out jobs requiring a high level of concentration and reliability. This negatively affects social and working aspects of pilots' lives, who have a high profile and a high-cost professional qualification. It could be possible now to revise this attitude thanks to the availability of Continuous Glucose Monitoring (CGM) devices. CGM clearly showed to prevent hypoglycemic events in insulin-treated diabetic patients by allowing strict monitoring and trend prediction of glucose levels. By systematizing available data on such devices and present regulations in CPL issuance worldwide, our review can be used as handy tool for a fruitful discussion among the scientific community, national and international civil aviation regulators, stakeholders and pilots, aimed at evaluating the evidence-based opportunity to revise CPL issuance criteria for insulin-treated diabetic pilots. For the above-mentioned reasons, there are, among the regulatory administrations of Civil Aviation around the globe, several different approaches and limitations set for the subjects with insulin-treated diabetes who want to obtain, or renew, a CPL.

Vitrification treatment of municipal solid waste bottom ash.

This study involves the chemical characterization of municipal solid waste (MSW) bottom ash (BA) produced at a combustor facility in Rimini (Italy), and vitrification experiments, performed at lab scale under atmospheric conditions, maximum temperature of 1100 °C, for different durations (2-16 h). LA-ICP-MS analyses of the glasses obtained revealed that the overall volatility of metal elements increases with the time but it cannot be simply predicted by element boiling point. Elements have been here categorized into three different groups depending on their volatility comparing the glass product with the BA starting sample- high, medium or low, respectively- (1) Cu, W, Cl; (2) Pb, Zn, Sr; (3) Mo, Cr, V, Ni. The behavior of Cs, Rb, Ag, Ba, Ga, Co, U, Zr, Hf and Ta in the glassy slag is not defined because we did not observe statistically significant changes in their volatility behavior. Vitrification allows us to produce chemically stable glassy materials and immobilize potentially harmful elements, thus producing from waste new vitreous materials that are relatively inert and suitable for potential re-utilization in new products and/or applications for building and construction industries. Moreover, the samples show REE chondrite-normalized patterns indicating relative enrichments in Light-Rare Earth Elements (LREE), in particular La and Nd which may be interesting from an economic point of view in terms of waste recovery. Thus, the results obtained show how to treat bottom ashes from incinerator in order to provide more chemically inert and economically useful resources for recycle and reuse of solid waste BA.

Timescales of water accumulation in magmas and implications for short warning times of explosive eruptions.

Water plays a key role in magma genesis, differentiation, ascent and, finally, eruption. Despite the recognized crucial function of water, there are still several issues that continue to blur our view about its role in magmatic systems. What are the timescales of H2O accumulation in crystallizing magmas? What are the ascent rates of water-rich residual melts leading to explosive eruptions? Here, we track the timescale of water accumulation in a residual melt resulting from crystallization of a hydrous CO2-bearing magmatic mass stored at mid- to deep-crustal levels in a subduction-related geodynamic setting. Our results indicate that, after a repose period ranging from few to several thousand years, water-rich melts with water concentrations larger than 6-9 wt.% can migrate towards the Earth surface in very short timescales, on the order of days or even hours, possibly triggering explosive eruptions with short warning times and devoid of long-term geophysical precursors.

Gastric emptying and intragastric balloon in obese patients.

BACKGROUND: Intragastric balloons have been proposed to induce weight loss in obese subjects. The consequences of the balloon on gastric physiology remain poorly studied. We studied the influence of an intragastric balloon on gastric emptying in obese patients. PATIENTS AND METHODS: 12 patients were included in the study, with BMI (mean +/- SD) of 38.51 +/- 4.32 kg/m2. The balloon was inserted under light anaesthesia and endoscopic control, inflated with 700 ml saline, and removed 6 months later. Body weight and gastric emptying (T1/2 and T lag) using 13C-octanoic acid breath test were monitored before balloon placement, during its permanence and 2 months after removal. RESULTS: Mean weight loss was: 6.2 +/- 2.3 kg after one month; 12.4 +/- 5.8 kg after 3 months; 14.4 +/- 6.6 kg after 6 months and 10.1 +/- 4.3 kg two months after BIB removal. Gastric emptying rates were significantly decreased in the first periods with balloon in place, and returned to pre-implantation values after balloon removal. T1/2 was: 87 +/- 32 min before BIB positioning, 181 +/- 91 min after 1 month, 145 +/- 99 min after 3 months, 104 +/- 50 min after 6 months and 90 +/- 43 min 2 months after removal. T lag was 36 +/- 18 min before BIB positioning, 102 +/- 82 min after 1 month, 77 +/- 53 min after 3 months, 59 +/- 28 min after 6 months and 40 +/- 21 min. 2 months after removal. CONCLUSIONS: BIB in obese patients seems to be a good help in following the hypo caloric diet, especially during the first three months when the gastric emptying is slower and the sense of repletion is higher. After this period gastric emptying starts to return to normal and the stomach adapts to BIB loosing efficacy in weight loss.

High-temperature apparatus for chaotic mixing of natural silicate melts.

A unique high-temperature apparatus was developed to trigger chaotic mixing at high-temperature (up to 1800 °C). This new apparatus, which we term Chaotic Magma Mixing Apparatus (COMMA), is designed to carry out experiments with high-temperature and high-viscosity (up to 10(6) Pa s) natural silicate melts. This instrument allows us to follow in time and space the evolution of the mixing process and the associated modulation of chemical composition. This is essential to understand the dynamics of magma mixing and related chemical exchanges. The COMMA device is tested by mixing natural melts from Aeolian Islands (Italy). The experiment was performed at 1180 °C using shoshonite and rhyolite melts, resulting in a viscosity ratio of more than three orders of magnitude. This viscosity ratio is close to the maximum possible ratio of viscosity between high-temperature natural silicate melts. Results indicate that the generated mixing structures are topologically identical to those observed in natural volcanic rocks highlighting the enormous potential of the COMMA to replicate, as a first approximation, the same mixing patterns observed in the natural environment. COMMA can be used to investigate in detail the space and time development of magma mixing providing information about this fundamental petrological and volcanological process that would be impossible to investigate by direct observations. Among the potentials of this new experimental device is the construction of empirical relationships relating the mixing time, obtained through experimental time series, and chemical exchanges between the melts to constrain the mixing-to-eruption time of volcanic systems, a fundamental topic in volcanic hazard assessment.

Differential expression of nuclear 11beta-hydroxysteroid dehydrogenase type 2 in mineralocorticoid receptor positive and negative tissues.

Corticosteroid hormone action is controlled at a pre-receptor level by the activity of two isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), catalyzing the interconversion of hormonally active cortisol to inactive cortisone. In particular 11beta-HSD2 protects the mineralocorticoid receptor (MR) from glucocorticoid excess, enabling aldosterone to interact with the MR. We have analyzed the subcellular localization of 11beta-HSD2 in relation to the expression of the MR in human colon and placenta. 3H-aldosterone binding studies confirmed expression of the MR in human colon but not term placental trophoblast. Enzyme activity studies and Western blot analyses carried out on subcellular fractions confirmed the presence of 11beta-HSD2 in microsomes. In colon, but not placenta, 11beta-HSD2 was also localized to the microsome-free, nuclear fraction. Protection upon the MR by 11beta-HSD2 in "classical" mineralocorticoid target tissues such as colon can be subserved at both a nuclear and extra-nuclear level. Tissue specific factors are responsible for the subcellular localization of 11beta-HSD2 and we postulate that one such factor may be the MR itself.

Immunodetection of 11 beta-hydroxysteroid dehydrogenase type 2 in human mineralocorticoid target tissues: evidence for nuclear localization.

11 beta-Hydroxysteroid dehydrogenase (11 beta HSI) is an enzyme complex responsible for the conversion of hormonally active cortisol to inactive cortisone; two isoforms of the enzyme have been cloned and characterized. Clinical observations from patients with the hypertensive syndrome apparent mineralocorticoid excess, recently explained on the basis of mutations in the human 11 beta HSD2 gene, suggest that it is the 11 beta HSD2 isoform that serves a vital role in dictating specificity upon the mineralocorticoid receptor (MR). We have raised a novel antibody in sheep against human 11 beta HSD2 using synthetic multiantigenic peptides and have examined the localization and subcellular distribution of 11 beta HSD2 in mineralocorticoid target tissues. The immunopurified antibody recognized a single band of approximately 44 kDa in placenta, trophoblast, and distal colon. In kidney tissue, two bands of approximately 44 and 48 kDa were consistently observed. No signal was seen in decidua, adrenal, or liver. Immunoperoxidase studies on the mineralocorticoid target tissues, kidney, colon, and parotid gland indicated positive staining in epithelial cells known to express the MR: respectively, renal collecting ducts, surface and crypt colonic epithelial cells, and parotid duct epithelial cells. No staining was seen in these tissues in other sites. The intracellular localization of 11 beta HSD2 in kidney and colon epithelial cells was addressed using confocal laser microscopy. Parallel measurements of 11 beta HSD2 and nuclear propidium iodide fluorescence on sections scanned through an optical section of approximately 0.1 micron indicated significant 11 beta HSD2 immunofluorescence in the nucleus. In human kidney, colon, and salivary gland, 11 beta HSD2 protects the MR from glucocorticoid excess in an autocrine fashion. Furthermore, within these tissues, 11 beta HSD2, which had been considered to be a microsomal enzyme, is also found in the nucleus, suggesting that the interaction between the MR and aldosterone or cortisol is in part a nuclear event.

Multiangle light scattering flow photometry of cultured human fibroblasts: comparison of normal cells with a mutant line containing cytoplasmic inclusions.

Multi-angle light scattering flow photometry was used to study the light scattering properties of normal cultured fibroblasts and a mutant fibroblast line containing cytoplasmic lysosomal inclusions. The effect of glutaraldehyde fixation on the light scattering properties of the cells was also examined and correlated with their ultrastructure. Normal fibroblasts showed uniform organelle distribution with few vacuoles or dense bodies in the cytoplasm while the mutant line showed abnormal cytoplasmic inclusions of varying morphology, density and lucency. As predicted by light scattering theory, the mutant cells containing the cytoplasmic inclusions scattered more light at large angles (greater than theta = 1.85 degrees) than did the normal cells. Glutaraldehyde fixation decreased light scattering at small angles (less than theta = 1.85 degrees), increased light scattering at larger angles (greater than theta = 1.85 degrees) in both normal and mutant cells and enhanced resolution of the light scattering signatures. The mutant line scattered 2-3 times more light at a wide angle (greater than theta = 12.74 degrees) than did the normal cells. These data suggest that abnormal lysosomal storage inclusion bodies in the cytoplasm of the cells can be detected by differential light scattering methods.

Enhanced expression of transforming growth factor beta1 in rat thyroid hyperplasia is thyrotropin induced and time dependent.

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta1, (TGF-beta1) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1): five after 2 weeks (PTU-2); five after 4 weeks (PTU-4); five after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment. PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta1 was performed in one lobe. while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta1 wits also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-beta1 within the thyrocytes is influenced by mitogen exposure time. A TGF-beta1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.

Mineral-associated hepatic injury: a report of seven cases with X-ray microanalysis.

The patterns of hepatic injury associated with various minerals were studied in seven patients. The subjects included one patient who was a sandblaster (silica by inhalation), one patient who was a dental laboratory technician (silica and chromium-cobalt alloy by inhalation), one patient with inhalational talcum powder abuse, and four chronic intravenous (IV) drug abusers (talc by IV injection). In all cases, the liver was examined by light and polarizing microscopy, and by scanning electron microscopy with energy-dispersive x-ray microanalysis. In the two patients with silica exposure, silica-containing sclerohyaline nodules were diffusely present in portal tracts and lobules. Both chromium-cobalt alloy and silica were present in the dental technician. In contrast, in all cases of talc exposure, aggregates of talc-laden macrophages were present in portal and centrilobular areas. Three IV drug abusers and the talcum powder abuser had histologic evidence of chronic hepatitis, most probably of viral etiology. We conclude that mineral type plays an important role in the pathogenesis and fibrogenesis of hepatic lesions. Compared with silica, talc primarily elicits a macrophage response without granuloma formation or fibrosis. Hepatic silicosis is a rare complication in dental laboratory technicians, and chromium-cobalt alloy may contribute to hepatic injury and fibrosis in this setting.

Carcinoma of the colon with undifferentiated, carcinoid, and squamous cell features.

An undifferentiated small cell tumor of the colon that was found by light- and electron-microscopic study to possess features of a malignant carcinoid merged into keratinizing squamous cell carcinoma. Single cells contained both dense-core secretory granules and tonofilaments. The implications of this combination in relation to theories of tumor origin and differentiation are briefly discussed.

Variation in subcapsular liver structure and its significance in the interpretation of wedge biopsies.

Wedge biopsies from the inferior border of the normal liver were studied in 72 cases. They were divided into three groups according to the extent and degree of capsular and subcapsular fibrous tissue. The changes were not sufficiently severe or extensive to cause confusion with nodular cirrhosis or to make wedge biopsy unreliable as a diagnostic tool.

Fatal cutaneous necrosis mimicking calciphylaxis in a patient with type 1 primary hyperoxaluria.

BACKGROUND: Cutaneous necrosis of the proximal lower extremities in a patient with end-stage renal disease is the classic presentation of calciphylaxis, an untreatable, rare, generally fatal necrotizing cutaneous syndrome. Type 1 primary hyperoxaluria (PH-1) usually presents in childhood with recurrent urolithiasis. Since enzymatic studies to confirm the metabolic defect are now available, some cases of idiopathic renal failure in adulthood have been shown to be caused by PH-1. These patients may develop vascular oxalate deposits resulting in livedo reticularis and distal acral vascular insufficiency. OBSERVATIONS: We describe a patient who presented in end-stage renal failure with proximal lower extremity cutaneous necrosis suggestive of calciphylaxis. A cutaneous biopsy specimen revealed oxalate crystals within blood vessels, and a diagnosis of PH-1 was confirmed enzymatically. CONCLUSIONS: This patient illustrates that PH-1 may present in adulthood, and, in the setting of cutaneous necrosis associated with end-stage renal disease, it may be confused with calciphylaxis. The importance of making a diagnosis of PH-1 is the potential ability to achieve long-term survival by reversing the underlying metabolic defect with hepatic transplantation.

TGF-beta 1 immunohistochemistry in goiter: comparison of patients with recurrence or no recurrence.

The aim of this work was to establish whether the immunohistochemical pattern for TGF-beta 1 in goiters that recur after thyroid surgery is different when compared with goiters that do not recur postoperatively. Twelve goiters, surgically removed by partial resection between 1977 and 1982, were studied. Ten years after surgery, 6 patients had recurrence of goiter or thyroid nodules (group 1); the others did not have any recurrence (group 2). The presence and location of TGF-beta 1 were evaluated a posteriori by immunohistochemistry in histological samples of the tissue that was removed. In each goiter specimen, 50 randomly selected subcapsular follicles were studied to evaluate the percentage of follicles negative or positive for TGF-beta 1 and the protein's intrathyrocyte location. In the slides of group 1, the percentage of TGF-beta 1-positive follicles was statistically (p < 0.01) greater (93.1%) than in group 2 (71.4%). No difference in the location of TGF-beta 1 was found. The authors found a greater percentage of positive follicles for the TGF-beta 1 protein in group 1 patients. In conclusion, TGF-beta 1 production in goiter is variable, time dependent, and may be a marker of active cellular proliferation due to chronic exposure to a goitrogen stimulus. Thus, the more TGF-beta 1 found, the more the cell is stimulated and, therefore, the greater the risk of relapse.

Apparent mineralocorticoid excess: type I and type II.

The syndrome of apparent mineralocorticoid excess (AME) is a heritable form of hypertension due to an inborn error of cortisol metabolism and is characterized by hypokalemia and low renin levels despite subnormal or normal levels of aldosterone and other known mineralocorticoids. The syndrome is attributable to congenital deficiency of the enzyme 11 beta-hydroxydehydrogenase (11 beta-HSD), which converts cortisol (F) to biologically inactive cortisone. This results in a prolonged half-life of F, which acts at the kidney level as a potent mineralocorticoid (MC). In fact, both F and aldosterone have similar affinities in vitro for type I MC receptor (MR), and 11 beta-HSD activity protects the MR in vivo from the higher circulating levels of F. The biochemical marker of this disorder is an increased ratio of tetrahydrocortisol (THF) + allo-THF/tetrahydrocortisone (THE) in the urine, which has been found in more than 20 patients described to date, together with evidence of a more general defect in steroid ring A reduction. Only a few cases (the so-called type II form) described in Italy differ from the classic form having a normal THF/THE ratio, but in both forms the ratio of free urinary F/E has recently been found to be similarly high. Dexamethasone is the treatment of choice but is often inadequate in long term control of high blood pressure. Acquired forms of AME are those consequent on abuse of licorice or carbenoxolone, which both inhibit 11 beta-HSD; the latter also inhibits the reverse 11-oxoreductase reaction leading to somewhat different abnormalities of urinary cortisol/cortisone. So far, two isoenzymes of 11 beta-HSD have been purified and cloned; 11 beta-HSD type 1 is NADP-dependent, abundant in liver, lung, and testis, and catalyzes both 11 beta-dehydrogenation and 11 beta-oxoreduction; no mutation in its gene was detected in patients with AME. A second NAD-dependent isoenzyme is present in kidney and placenta and catalyzes dehydrogenation only. Very recently (1995) two groups have independently demonstrated the presence of mutations in its gene, located in chromosome 16q22. New and co-workers found a point mutation in exon 6 of two affected siblings of an Iranian family, while White and co-workers in parallel studies showed point mutations or small deletions in both alleles in nine unrelated patients; importantly, expression studies showed minimal or absent activity for almost all the mutant sequences. No definite mutations have been so far identified in patients with AME type II. AME is thus the third single gene cause of human hypertension to be described, after glucocorticoid remediable aldosteronism in 1992 and Liddle's syndrome in 1994.

Hindsight bias: an impediment to accurate probability estimation in clinicopathologic conferences.

Although clinicopathologic conferences (CPCs) have been valued for teaching differential diagnosis, their instructional value may be compromised by hindsight bias. This bias occurs when those who know the actual diagnosis overestimate the likelihood that they would have been able to predict the correct diagnosis had they been asked to do so beforehand. Evidence for the presence of the hindsight bias was sought among 160 physicians and trainees attending four CPCs. Before the correct diagnosis was announced, half of the conference audience estimated the probability that each of five possible diagnoses was correct (foresight subjects). After the correct diagnosis was announced the remaining (hindsight) subjects estimated the probability they would have assigned to each of the five possible diagnoses had they been making the initial differential diagnosis. Only 30% of the foresight subjects ranked the correct diagnosis as first, versus 50% of the hindsight subjects (p less than 0.02). Although less experienced physicians consistently demonstrated the hindsight bias, more experienced physicians succumbed only on easier cases.

Renal lipidosis associated with arteriohepatic dysplasia (Alagille's syndrome).

We report a 20-year-old patient with arteriohepatic dysplasia (Alagille's syndrome) who developed progressive renal failure associated with extensive renal lipidosis. A renal biopsy showed diffuse thickening of glomerular basement membrane mimicking idiopathic membranous glomerulonephritis on light microscopy. Electron microscopy, however, demonstrated numerous intramembranous and mesangial lipid deposits, quite similar to those described in familial lecithin cholesterol acyltransferase deficiency. We believe the renal lipidosis developed secondary to hyperlipidemia associated with longstanding intrahepatic cholestasis. This case illustrates that extensive lipid deposition in the glomerular basement membrane may occur in patients with arteriohepatic dysplasia, and it may lead to progressive renal failure.