Search

With 64,050 new diagnoses and 50,550 deaths in the US in 2023, pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all human malignancies. Early detection and improved prognostication remain critical unmet needs. We applied next-generation metabolomics, using quantitative tandem mass spectrometry on plasma, to develop biochemical signatures that identify PDAC. We first compared plasma from 10 PDAC patients to 169 samples from healthy controls. Using metabolomic algorithms and machine learning, we identified ratios that incorporate amino acids, biogenic amines, lysophosphatidylcholines, phosphatidylcholines and acylcarnitines that distinguished PDAC from normal controls. A confirmatory analysis then applied the algorithms to 30 PDACs compared with 60 age- and sex-matched controls. Metabolic signatures were then analyzed to compare survival, measured in months, from date of diagnosis to date of death that identified metabolite ratios that stratified PDACs into distinct survival groups. The results suggest that metabolic signatures could provide PDAC diagnoses earlier than tumor markers or radiographic measures and offer insights into disease severity that could allow more judicious use of therapy by stratifying patients into metabolic-risk subgroups.

This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds 4a - l , via a convenient one-pot three-component Hantzsch reaction. This approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, and interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as a promising compound, demonstrating robust antioxidant activity, the ability to activate Nrf2-ARE pathways, as well as calcium channel blockade and cathepsin S inhibition. Dihydropyridine 4i represents the first example of an MTDL that combines these biological activities.

Introduction: Alzheimer's disease (AD) is a progressive, irreversible, and multifactorial brain disorder that gradually and insidiously destroys individual's memory, thinking, and other cognitive abilities., Areas Covered: In this perspective, the authors examine the complex and multifactorial nature of Alzheimer's disease and believe that the best approach to develop new drugs is the MTDL strategy, which obviously faces several challenges. These challenges include identifying the key combination of targets and their suitability for coordinated actions, as well as developing an acceptable pharmacokinetic and toxicological profile to deliver a drug candidate., Expert Opinion: Since calcium plays a crucial role in the pathology of AD, a polypharmacological approach with calcium channel blockers reinforced by activities targeting other factors involved in AD is a serious option in our opinion. This is exemplified by a phase III clinical trial using a drug combination approach with Losartan, Amlodipine (a calcium channel blocker), and Atorvastatin, as well as several MTDL-based calcium channel blockade approaches with a promising in vitro and in vivo profile.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.

Background: TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in "hotspots" affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to P53 cysteine residues, altering conformation, while COTI-2 showed activity in P53 mutant tumors by a computational platform. We compared APR-246 and COTI-2 activity in human tumor explants from 247 surgical specimens. Methods: Ex vivo analyses of programmed cell death measured drug-induced cell death by delayed-loss-of-membrane integrity and ATP content. The LC50s were compared by Z-Score. Synergy was conducted by the method of Chou and Talalay, and correlations were performed by Pearson moment. Results: APR-246 and COTI-2 activity favored hematologic neoplasms, but solid tumor activity varied by diagnosis. COTI-2 and APR-246 activity did not correlate (R = 0.1028) (NS). COTI-2 activity correlated with nitrogen mustard, cisplatin and gemcitabine, doxorubicin and selumetinib, with a trend for APR-246 with doxorubicin. For ovarian cancer, COTI-2 showed synergy with cisplatin at 25%. Conclusions: COTI-2 and APR-246 activity differ by diagnosis. A lack of correlation supports distinct modes of action. Cisplatin synergy is consistent with P53's role in DNA damage. Different mechanisms of action may underlie disease specificity and offer better disease targeting.

Novel multitarget-directed ligands BIGI 4a-d and BIGI 5a-d were designed and synthesized with a simple and cost-efficient procedure via a one-pot three-component Biginelli reaction targeting acetyl-/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Among these multitarget-directed ligands, BIGI 4b, BIGI 4d, and BIGI 5b were identified as promising new hit compounds showing in vitro balanced activities toward the recognized AD targets. In addition, these compounds showed suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software.

Ten new differently substituted 3-benzyl-5-aryl-3,5-dihydro-4 H -benzo[6,7]chromeno[2,3- d ]pyrimidin-4,6,11-triones 3 were synthesized by a simple and cost-efficient procedure in a one-pot, three-component reaction from readily available ethyl 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4 H -benzo[ g ]chromene-3-carboxylates, benzylamine and triethyl orthoformate under solvent- and catalyst-free conditions. All the new compounds were screened for their antiproliferative activity against two colorectal-cancer-cell lines. The results showed that the compounds 3-benzyl-5-phenyl-3,5-dihydro-4 H -benzo[6,7]chromeno[2,3- d ]pyrimidine-4,6,11-trione ( 3a ) and 3-benzyl-5-(3-hydroxyphenyl)-3,5-dihydro-4 H -benzo[6,7]chromeno[2,3- d ]pyrimidine-4,6,11-trione ( 3g ) exhibited the most potent balanced inhibitory activity against human LoVo and HCT-116 cancer cells.

Objective: Platinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic signatures that predict platinum resistance in patients receiving chemotherapy for gynecologic cancers., Methods: In this study 47 patients with adenocarcinoma of the ovary or uterus who were candidates for carboplatin plus paclitaxel submitted blood for quantitation of metabolites and surgical specimens for the isolation 3-dimensional organoids used to measure individual patient platinum resistance, ex vivo. Results were correlated with response, time to progression and survival., Results: Of 47 patients, 27 (64.3%) achieved complete remission with a mean time to progression of 1.9 years (± 1.5), disease-free survival of 1.7 years (± 1.4) and overall survival of 2.6 years (± 1.6) and a mean cisplatin lethal concentration 50% (LC50) = 1.15 μg/ml (range 0.4-3.1). Cisplatin LC50's correlated with a non-significant decrease in complete remission (RR [95% CI] =0.76 [0.46-1.27]), diminished disease-free survival (median: 1.15 vs. 2.99 years, p = 0.038) and with biochemical signatures of 186 metabolites. Receiver operating curves (ROC) of lipid ratios, branched chain amino acids and the tryptophan to kynurenine ratio identified patients at the highest risk of relapse and death (AUC = 0.933) with a sensitivity of 92.0% and specificity of 86.0% (p < 0.001)., Conclusions: Metabolic signatures in gynecologic cancer identify patients at the highest risk of relapse and death offering new diagnostic and prognostic tools for management of the advanced gynecologic tumors., Competing Interests: Declaration of Competing Interest Krishnansu S. Tewari, Robert E. Bristow, Fabio Cappuccini, Marcia B. Salzgeber, Anton M. Palma, Dirce M. L. Marchioni, Antonio A.F. Carioca, Kristine R. Penner, Jill Alldredge and Teresa Longoria have no conflicts of interest to declare. Paulo D'Amora (research grants from funding agencies: São Paulo Research Foundation (FAPESP); financial support for attending symposia and for educational programs: Nagourney Cancer Institute, American Association for Cancer Research, Rivkin Center; consultation: Metabolomycs, Inc.; intellectual property rights: Metabolomycs, Inc.; stockholder: Metabolomycs, Inc.). Steven S. Evans (employment: Nagourney Cancer Institute; stockholder: Metabolomycs, Inc.). Paula J. Addis-Bernard (employment: Nagourney Cancer Institute). Ismael Dale C.G. Silva (board director: Metabolomycs, Inc.; stockholder: Metabolomycs, Inc.). Robert A. Nagourney (board director: Nagourney Cancer Institute and Metabolomycs, Inc.; stockholder: Metabolomycs, Inc.). We certify that the submission is original work and is not under review at any other publication., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Data have shown that healthy children and adolescents have an inadequate intake of zinc, an essential nutrient for growth. It is unclear whether zinc supplementation can enhance bone health during this rapid period of growth and development., Objective: The primary aim of this study was to determine the effect of zinc supplementation on biochemical markers of bone turnover and growth in girls entering the early stages of puberty. The secondary aim was to test moderation by race, body mass index (BMI) classification, and plasma zinc status at baseline., Methods: One hundred forty seven girls aged 9-11 y (46% black) were randomly assigned to a daily oral zinc tablet (9 mg elemental zinc; n = 75) or an identical placebo (n = 72) for 4 wk. Fasting plasma zinc, procollagen type 1 amino-terminal propeptide (P1NP; a bone formation marker), carboxy-terminal telopeptide region of type 1 collagen (ICTP; a bone resorption marker), and insulin-like growth factor I (IGF-I) were assessed at baseline and post-test. Additional markers of bone formation (osteocalcin) and resorption (urinary pyridinoline and deoxypyridinoline) were also measured., Results: Four weeks of zinc supplementation increased plasma zinc concentrations compared with placebo [mean change, 1.8 μmol/L (95% CI: 1.0, 2.6) compared with 0.2 μmol/L (95% CI: -0.3, 0.7); P < 0.01]. Zinc supplementation also increased serum P1NP concentrations compared with placebo [mean change, 23.8 μmol/L (95% CI: -14.9, 62.5) compared with -31.0 μmol/L (95% CI: -66.4, 4.2); P = 0.04). There was no effect from zinc supplementation on osteocalcin, ICTP, pyridinoline, deoxypyridinoline, or IGF-I. There was no moderation by race, BMI classification, or plasma zinc status at baseline., Conclusions: Our data suggest that 4 wk of zinc supplementation increases bone formation in premenarcheal girls. Further studies are needed to determine whether supplemental zinc can improve childhood bone strength. This trial was registered at clinicaltrials.gov as NCT01892098., (© 2015 American Society for Nutrition.)

Purpose: This study aims to report on the measured in vivo contribution of soft lenses of various powers to the optics of a piggyback system (PBS)., Methods: This prospective, non-dispensing clinical study was conducted on regular wearers of contact lenses who showed regular corneal profiles. Subjects were masked to the products used. The study involved the use of a spherical soft lens of three different powers in a PBS, used as a carrier for a rigid gas permeable lens. Baseline data were collected and soft lenses were then fitted on both eyes of each subject. Both lenses were assessed for position and movement. Over-refraction was obtained. Soft lens power contribution to the optics (SLPC) of a PBS system was estimated by computing initial ametropia, lacrymal lens, rigid lens powers and over-refraction. A set of data on one eye was kept, for each subject, for statistical analysis., Results: Thirty subjects (12 males, 18 females), aged 24.4 (±4.5) years, were enrolled. The use of plus powered soft lenses enhanced initial RGP lens centration. Once optimal fit was achieved, all lenses showed normal movement. SLPC represented 21.3% of the initial soft lens power when using a -6.00 carrier, and 20.6% for a +6.00. A +0.50 did not contribute to any power induced in the system. These results are generally in accordance with theoretical model developed in the past., Conclusion: On average, except for the low-powered carrier, the use of a spherical soft lens provided 20.9% of its marked power. To achieve better results, the use of a plus-powered carrier is recommended., (Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Though adolescents consume more fructose than any other age group, the relationship between fructose consumption and markers of cardiometabolic risk has not been established in this population. We determined associations of total fructose intake (free fructose plus one-half the intake of free sucrose) with cardiometabolic risk factors and type of adiposity in 559 adolescents aged 14-18 y. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, and C-reactive protein. Diet was assessed with 4-7 24-h recalls and physical activity (PA) was determined by accelerometry. Fat-free soft tissue (FFST) mass and fat mass were measured by DXA. The s.c. abdominal adipose tissue (SAAT) and visceral adipose tissue (VAT) were assessed using MRI. Multiple linear regression, adjusting for age, sex, race, Tanner stage, FFST mass, fat mass, PA, energy intake, fiber intake, and socioeconomic status, revealed that fructose intake was associated with VAT (β = 0.13; P = 0.03) but not SAAT (P = 0.15). Significant linear upward trends across tertiles of fructose intake were observed for systolic blood pressure, fasting glucose, HOMA-IR, and C-reactive protein after adjusting for the same covariates (all P-trend < 0.04). Conversely, significant linear downward trends across tertiles of fructose intake were observed for plasma HDL-cholesterol and adiponectin (both P-trend < 0.03). When SAAT was added as a covariate, these trends persisted (all P-trend < 0.05). However, when VAT was included as a covariate, it attenuated these trends (all P-trend > 0.05). In adolescents, higher fructose consumption is associated with multiple markers of cardiometabolic risk, but it appears that these relationships are mediated by visceral obesity.

The aim of the present study was to propose a model and a method to derive the oxyhemoglobin blood content in the retinal veins and arteries by full spectrum reflectometry measurements in the spectral zone from 430 to 680 nm. We proposed a mathematical equation expressed as a linear combination of two terms S(OHb)(λ) and S(Hb)(λ) representing the normalized spectral absorption functions of the hemoglobin and the oxyhemoglobin, one term λ(-n) representing the ocular media absorption with scattering, and a family of multi-Gaussian functions, which usefully compensate for the noncompatibility of the model and the experimental data in the red spectral zone. The present paper suggests that the spectral reflection function in the area from 520 to 580 nm is optimal in calculating the oxyhemoglobin concentration of the blood contained in the endothelial structures of retinal vessels. The model calculation needs a function (1/λ)(-n) that corrects for the ocular media absorption and light scattering on the vessels' structures. For the spectral area of lights with wavelength larger than 580 nm, the reflected light represents mainly the light scattering on the red blood cells.

Context: Although animal studies suggest that it is the uncarboxylated rather than carboxylated form of osteocalcin that affects glucose homeostasis, the human data are scant and equivocal., Objective: This study investigated associations of uncarboxylated and carboxylated forms of osteocalcin with insulin sensitivity and β-cell function in 140 overweight prepubertal children (43% female, 46% black, 84% obese) with normal glucose levels (n = 99) and prediabetes (n = 41)., Methods: An oral glucose tolerance test was used to identify prediabetes and for measurement of insulin sensitivity (Matsuda index), β-cell function [oral glucose tolerance test derived insulinogenic index and disposition index (DI(OGTT))] and uncarboxylated and carboxylated forms of osteocalcin. Visceral adipose tissue (VAT) was assessed using magnetic resonance imaging., Results: After controlling for age, sex and race, lower uncarboxylated osteocalcin concentrations, Matsuda index, insulinogenic index, and DI(OGTT) and higher VAT levels were found in the prediabetes vs. normal-glucose group (all P < 0.03). Carboxylated osteocalcin levels were not different between groups. Multiple linear regression adjusting for age, sex, race, and VAT revealed that uncarboxylated osteocalcin was associated with insulinogenic index and DI(OGTT) (β = 0.34, 0.36, respectively, both P < 0.04) in the prediabetes group but not the normal-glucose group. In both the normal-glucose and prediabetes groups, carboxylated osteocalcin was associated with insulin sensitivity (β = 0.26, 0.47, respectively, both P < 0.02)., Conclusions: These data suggest that the lower uncarboxylated osteocalcin concentrations found in children with prediabetes may be associated with β-cell dysfunction. In addition, our findings between carboxylated osteocalcin and insulin sensitivity suggest that carboxylated osteocalcin plays a role in human glucose homeostasis.

Objective: To compare bone mass between overweight adolescents with and without cardiometabolic risk factors (CMR). Associations of bone mass with CMR and adiposity were also determined., Study Design: Adolescents (aged 14 to 18 years) who were overweight were classified as healthy (n = 55), having one CMR (1CMR; n = 46), or having two or more CMR (≥2CMR; n = 42). CMRs were measured with standard methods and defined according to pediatric definitions of metabolic syndrome. Total body bone mass, fat mass, and fat-free soft tissue mass were measured with dual-energy X-ray absorptiometry. Visceral adipose tissue and subcutaneous abdominal adipose tissue were assessed with magnetic resonance imaging., Results: After controlling for age, sex, race, height, and fat-free soft tissue mass, the healthy group had 5.4% and 6.3% greater bone mass than the 1CMR and ≥2CMR groups, respectively (both P values <.04). With multiple linear regression, adjusting for the same co-variates, visceral adipose tissue (β = -0.22), waist circumference (β = -0.23), homeostasis model assessment of insulin resistance (β = -0.23), and high-density lipoprotein cholesterol level (β = 0.22) were revealed to be associated with bone mass (all P values <.04). There was a trend toward a significant inverse association between bone mass and fasting glucose level (P = .056). No relations were found between bone mass and fat mass, subcutaneous abdominal adipose tissue, blood pressure, or triglyceride level., Conclusion: Being overweight with metabolic abnormalities, particularly insulin resistance, low high-density lipoprotein cholesterol level, and visceral adiposity, may adversely influence adolescent bone mass., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Childhood studies of the fat-bone relationship are conflicting, possibly reflecting the influence of metabolic abnormalities in some but not all obese children. Bone mass was compared between prepubertal overweight children with (n = 41) and without (n = 99) prediabetes. Associations of bone mass with measures of total and central adiposity, glucose intolerance, insulin sensitivity, lipid profile, systemic inflammation, and osteocalcin also were determined. In 140 overweight children aged 7 to 11 years, an oral glucose tolerance test was used to identify those with prediabetes and for determination of glucose, 2-hour glucose, glucose area under the curve (AUC), insulin, 2-hour insulin, and insulin AUC. Blood samples also were assessed for lipids, C-reactive protein, and osteocalcin. Total-body bone mineral content (BMC), fat-free soft tissue mass (FFST), and fat mass (FM) were measured by dual-energy X-ray absorptiometry (DXA). Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were assessed using MRI. Total-body BMC was 4% lower in overweight children with prediabetes than in those without prediabetes after controlling for sex, race, height, and weight (p = .03). In the total sample, FM was positively related with BMC (β = 0.16, p = .01) after adjusting for sex, race, height, and FFST. However, VAT (β = -0.13, p = .03) and SAAT (β = -0.34, p = .02) were inversely associated with BMC after controlling for sex, race, height, FFST, FM, and SAAT or VAT. No significant associations were found between BMC and the biochemical measurements. Prepubertal overweight children with prediabetes may be at risk for poor skeletal development. In addition, it appears that greater levels of central rather than total adiposity may be deleterious for developing bone., (Copyright © 2010 American Society for Bone and Mineral Research.)

Healthcare organizations that deliver high quality care as efficiently as possible inevitably are profitable. In the eleventh installment of Straight Talk, we discuss the performance improvement strategies of three health systems that strive to strike a balance between financial and altruistic goals: 15 hospital, $1.4-billion St. Vincent Health, Indianapolis, IN., formerly Central Indiana Health System and owned by Ascension Health, St. Louis.; 7 hospital, $1.8-billion Detroit Medical Center.; 3-hospital, $500-million Bon Secoure Richmond Health System, Richmond Va., which is part of Bon Secours Health System Inc., Marriottsville, Md. Modern Healthcare and PricewaterhouseCoopers present Straight Talk. The session on performance improvement was held on January 15, 2003 at Modern Healthcare's Chicago headquarters Fawn Lopez, associate publisher of Modern Healthcare, was the moderator.

Cine-MRI demonstrates the presence of mitral regurgitation by a signal void. This study was undertaken to assess the value of this method for quantification of mitral regurgitation in a population not excluding either patients with mitral valve prostheses or those with atrial fibrillation. The subjects included had a mean age of 59 years and were referred for transoesophageal echocardiography, either for assessment of valvular heart disease (38 patients), or for detection of atrial thrombosis before external electrical cardioversion (7 patients). Eight patients had mitral valve prostheses and 19 were in atrial fibrillation. Cine-MRI was performed within 12 days of the transoesophageal echocardiography study with a 1.5 tesla magnet, using a sequence of gradient echo in 3 parallel planes in the 4 chamber view. The regurgitation was quantified by MRI from the extension of the signal void in the left atrium. The transoesophageal Doppler echocardiographic criteria were the width of the regurgitant jet at its origin, the intensity of the regurgitation signal recorded by continuous wave Doppler and the extension of the jet within the left atrium. The quantification by degrees 1 to 4 did not differ by more than 1 degree between the 2 techniques in 43 of the 45 patients. Out of 4 left atrial thrombus detected by transoesophageal echocardiography, only 1 was visible by MRI. The authors concluded that quantification of mitral regurgitation by cine-MRI provides similar results to those obtained by transoesophageal echocardiography and that the correlation remains valid in cases of atrial fibrillation. However, Doppler echocardiography provides further valuable information for the clinician.

Objective: Assessment of coronary bypass patency with conventional angiography can be limited by difficulties in selective catheterism. The aim of this work was to determine whether ultrarapid sequences proposed for imaging coronary arteries could be used to evaluate bypass patency., Methods: Twenty patients (mean age 66 +/- 7 years) with 42 aorto-coronary bypasses (32 venous and 10 mammary bypasses) underwent conventional angiography and magnetic resonance angiography within a 1 week interval. All patients were evaluated 1 to 15 years after bypass surgery. Magnetic resonance imaging (MRI) was performed in ventral supine position using a flexible surface coil. Breathhold electrocardiogram-synchronized sequences were acquired using a 1.5 T magnet, with TR = 156 ms, TE = 8 ms, slice thickness 5 mm, 126.256 matrix, and a 7 to 11 segmentation per cardiac cycle. At most, 24 transverse slices were acquired for each patient., Results: Twenty-six patent bypasses were correctly identified with MRI. Three bypass were patent on angiography and appeared occluded on MRI (2 mammary and 1 venous bypass). Nine bypasses were classed as occluded with both techniques. MRI demonstrated patency in one bypass for which selective catheterism was not possible. The sensitivity of MRI for the diagnosis of patency in aorto-coronary bypasses was 89% with a 92% specificity. MRI did not identify 1 out of 4 bypass stenoses., Conclusion: We conclude that the ultrarapid breath-hold magnetic resonance sequences can be used to determine patency of aorto-coronary bypasses with good sensitivity and specificity. Our results would suggest however that this method is inadequate for the diagnosis of bypass stenosis.

The authors report a long term success of bipulmonary transplantation in a 15 year old girl with cystic fibrosis and respiratory failure complicated by severe right heart failure. The operation did not cause any particular problems. After transplantation, the clinical signs of right ventricular failure and echocardiographic right ventricular dilatation regressed in less than one week. The right ventricular hypertrophy also regressed. Echocardiography shows no abnormality after 5 years' follow-up.

The different methods of measurement of red blood cell and plasma volumes are exposed. The "Gold Standard" remains the measurement of whole blood volume with 51 chromium labelled red cells and the calculation of red blood cell and plasma volumes with the result of microhematocrit. In some cases, the direct measurement of plasma volume is performed with 125 I-human serum albumin. The mode of expression of the experimental results of blood volume is discussed. Two main modes are employed: expression as a function of the body weight (ml/kg) or as a percent of the value of a normal subject (same age and body area). The usefulness of measurement of red cell and plasma volumes in the diagnosis of true and apparent polycythemia is discussed.

This study was undertaken to determine the prognostic value of exercise myocardial scintigraphy in hypertension patients suspected of coronary disease. One hundred and thirty six hypertension patients (mean age: 59) suspected of coronary disease were monitored for 46 months after thallium 201 exercise myocardial scintigraphy (tomographic mode). Prognostic factors analysed were clinical (typical nature of pain, exercise blood pressure), electrocardiographic (presence of repolarisation abnormalities in resting ECG), ergometric (electrically positive test) and scintigraphic (existence or not of transitory hypofixation). Events sought were: death of coronary origin, non-fatal myocardial infarction, aorto-coronary bypass and coronary angioplasty. One-way analysis showed that the existence of transitory hypofixation by scintigraphy, positive exercise electrocardiogram and typical angina pain enabled the prediction of coronary events. Thus 14 of 36 patients (39%) with transitory or combined hypofixation had a coronary event as against 7 of the 100 patients without transitory hypofixation. Only the existence of transitory hypofixation retained a prognostic value for coronary events by multivariate analysis (relative risk = 5.4, p = 0.001). It was also found that the prognosis was good when scintigraphy did not reveal transitory hypofixation while exercise testing was positive (2 coronary events/27 patients). It is concluded that, despite the possibility of "false positives", linked in particular to myocardial hypertrophy, myocardial scintigraphy offers better prediction of coronary events in hypertension patients that other clinical or electrocardiographic parameters.

Background: The cardiac involvement in cystic fibrosis includes the rare cardiomyopathy seen in infants and changes in left ventricular performance in older children., Population and Methods: 67 patients, 6 to 34 months-old (mean: 16.7), 37 male and 30 female, with cystic fibrosis, were studied. Their Shwachman score was < 70. None showed any clinical manifestations of left ventricular insufficiency, but 6 patients had right ventricular insufficiency. Echocardiography was performed on 58 patients; it showed dilation of the right ventricle in 32 of them. Left ventricular perfusion was studied with thallium 201 tomoscintigraphy and left ventricular ejection fraction with 99mTc ventriculography., Results: The left ventricular ejection fraction was < 45% in 17 patients and scintigraphy showed hypofixation in 6 of them. In contrast, only 4 of the 50 patients with left ventricular ejection fraction > 45% had thallium hypofixation., Conclusions: Resting perfusion abnormalities are more frequent in patients with a low left ventricular ejection fraction. These perfusion abnormalities suggest that myocardial fibrosis complicates the advanced stages of cystic fibrosis.

In patients with thalassemia treated by long-term chronic blood transfusions who survive beyond the first ten or twenty years of life but received no or inadequate chelating therapy during the first years, evaluation of iron overload and its consequences on tissues may prove an arduous task. MRI is a non-invasive means of measuring the amount of iron in the liver and the consequences of the iron overload on the heart and other tissues. For this purpose, MRI is more satisfactory than CT scan studies. In this investigation, 20 patients with thalassemia major underwent MRI. Multiple spin echos were used to allow determination of the transversal relaxation constant T2. This constant, expressed in ms, is related to the concentration of iron in the liver as in the following expression: (C) = 5 410/T2-110. MRI studies disclosed a discrepancy between the severity of hepatic hemosiderosis and development of decompensated iron overload cardiomyopathy. In a unique case, in which a heart transplant and two MRI studies were performed, the severe iron overload that failed to respond to several years of subcutaneous chelating therapy was more than halved by intensive intravenous chelation through a central catheter. MRI studies of the heart provide valuable morphologic and functional data. Although the amount of iron in the myocardium cannot as yet be quantified, modifications of the transversal relaxation time provide information on the severity of the overload and the presence of other myocardial alterations.

Chronic pericarditis can take the form of localised annular bands constricting the atrioventricular grooves, the pulmonary infundibulum and, rarely, the atria. The authors report two cases of pericardial bands surrounding the ventricles and involving the atrioventricular groove resulting in a biloculation of the left ventricle. One case was complicated by adiastole and one by mitral regurgitation due to involvement of the posterior mitral leaflet. Magnetic resonance imaging gave precise definition of these bands and of their extension into the myocardium. This investigation was a valuable complement before surgery of the localised constriction.

Ten patients with acute myocardial infarction were studied by magnetic resonance imaging (MRI) with injection of a paramagnetic contrast agent: Gadolinium-DOTA (Gd-DOTA). The time interval between the onset of symptoms and MRI was 8 to 12 days. The site of infarction was determined in all cases by Thallium 201 scintigraphy (hypofixation) and selective ventriculography (segmental wall anomalies): anterior (6 cases), inferior (4 cases). MRI was performed with a 0.5 Tesla CGR Magniscan by the multiple spin technique. A series of tomographic sections was recorded immediately after intravenous injection of 0.4 mmol/Kg of Gd-DOTA. Recent myocardial infarction with parenchymal oedema gives an enhanced transmural signal: only 3 patients had a sufficiently contrasted image on the 1st spin echo. After Gd-DOTA, 7 patients had significantly increased contrast on this echo and in all excellent contrast between infarcted and healthy myocardium was obtained in 9 of the 10 patients. There was excellent correlation concerning the site of infarction between Thallium scintigraphy and left ventriculography. The intensity of signal and T2 relaxation time of different myocardial segments was studied by the regions of interest technique: the ratio of signal intensity of infarcted/healthy myocardium was 1.3 before and 1.7 after Gd-DOTA on first spin echo images. The mean T2 was 54.1 +/- 9 ms in healthy and 82 +/- 28 ms in infarcted myocardium. After Gd-DOTA, both values decreased and tended to equalize.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of sternocleidomastoid tumor of infancy in a 1-month-old boy is presented. Fine-needle aspiration biopsy can be used to confirm the diagnosis and thereby avoid more invasive procedures. Early diagnosis and treatment are important factors in achieving a good clinical outcome.

Dipyridamole thallium scintigraphy (tomo SMTD) (fig. 2) and a bicycle stress-testing ECG were performed in a prospective study of 102 patients (Tabl. VIII) referred for aortic reconstruction surgery with aortic cross-clamping (fig. 1), carried out without knowledge of tomo SMTD results. A clinical coronary artery disease (CAD) was suspected in 45 patients (44%). The exercise test (tabl. IV) was inadequate in 78%, normal in 11% and abnormal in 11% of patients. Tomo SMTD (tabl. VI et X) was normal in 60 patients (59%), abnormal with persistent defect in 21 (20.5%) and abnormal with transient defect in 21 (20.5%). Post-operative cardiac events (tabl. I) occurred in 4 patients (3.9%): 2 deaths, 1 non-fatal myocardial infarction and 1 rest angina; but only 2 of these had documented CAD. All 4 had abnormal tomo SMTD (3 with transient, 1 with persistent defect). It is concludes that abnormal tomo SMTD had a significant pronostic value (p less than 0.03) in predicting post-perative cardiac events (tabl. XI, fig. 3) after abdominal aortic surgery with cross-clamping. This test facilitates selection of patients for coronary angiography.

Forty-five patients (35 men, 10 women) undergoing carotid surgery had Indium-111 platelet scintigraphy as part of their preoperative work-up. Imaging was performed within three hours after injection of the Indium-111. A second series of views was obtained 24 hours later and repeated at 24 hour intervals for two days. Of 54 scintigrams, 22 were positive and 32 negative. Positive results were defined as a twofold or more increase in local activity on a visualized carotid after 24 hours. The sensitivity of the method was 41%, intraoperatively, and the specificity, 100%. The low sensitivity places this method behind sonography and duplex-scanning for screening patients for surgery. We believe that indications for platelet scintigraphy are limited to: 1. Repeated transient ischemic attacks in the same territory with minimal lesions on arteriography and non-homogeneous plaque on duplex scan; 2. Symptomatic patients being treated medically as a possible argument for surgery; 3. Determining therapeutic policy for patients having experienced a transient ischemic attack with a coexisting intracardiac thrombus.

Three methods of diagnostic imaging : bi-dimensional ultrasonography, scanography and 111Indium-labelled platelet scintigraphy were compared in 61 patients to detect left intraventricular thrombotic lesions, in order to determine their respective diagnostic values.

The aim of this study was to use scintigraphy with Indium III marked platelets to detect intracardiac thrombi. Platelet marking was performed with the patient's own platelets and Indium III oxinate. The date was recorded and treated with a gamma-camera-computer system. The results obtained in 45 patients (36 male, 9 female, aged 38 to 80 years, mean age 61 years) were compared with those of 2D echocardiography in all cases, and with CAT in 30 cases. Seventeen patients (13 myocardial infarcts, 2 cardiomyopathies with dilatation, 2 mitral stenoses) were considered to have intracardiac thrombi on platelet scintigraphy with foci of hyperfixation increasing with time, clearly distinguishable from circulating cardiac activity. Sixteen of these cases had appearances of thrombosis on 2D echo (14 left ventricle, and 2 left atrium) and 12 cases had a triple positive result (2D echo, CAT and platelet scintigraphy). One patient had positive platelet scintigraphy and negative 2D echo and CAT. In the 24 cases with negative platelets scintigraphy, an intracardiac thrombus was demonstrated by 2D echo and CAT scanning in 2 cases. Two out of 4 patients with transient hyperfixation had appearances of a large chronic thrombus on 2D echo and CAT. The efficacy of therapy was monitored in 3 patients on heparin and 4 patients on platelet antiaggregants. These results show that platelet scintigraphy is a highly specific method of detecting intracardiac thrombi. It is less sensitive than 2D echo because it depends on the haematological activity of the thrombus, making it a useful technique for assessing the efficacy of therapy.

A group of 87 patients with inverted papilloma, a locally aggressive benign sinonasal tumor, were treated over the past 15 years. Selection of therapy depends on an accurate radiographic assessment of the extent of tumor. The tumor's local aggressiveness, high rate of recurrence, associated malignancy, and multicentric tendency have led most workers to advocate radical surgical removal of the tumor by lateral rhinotomy and en bloc resection of the ethmoid labyrinth. Radiographic evaluation by computed tomography scanning and magnetic resonance imaging permits identification of a small group of patients who have limited lesions and may be candidates for conservative tumor resection by intranasal or transantral sphenoethmoidectomy. Among our ten patients treated with conservative surgery, there was recurrence in one case (10%). Seventy-five patients underwent rhinotomy and medial maxillectomy, with seven cases recurring (9%). The overall recurrence rate was 9% (8 of 87). Among the 87 cases, 5 patients had carcinoma (6%). The literature is reviewed and the principles of case selection and management are discussed.

Patients with AIDS or ARC may present with parotid gland enlargement either initially or during the course of their disease. Of nine such patients, eight had unilateral gland enlargement, and one had bilateral disease. CT and MR scanning revealed that all patients except one had bilateral multiple intraparotid cysts. In addition, four of the nine patients clinically had cervical adenopathy, while all patients had adenopathy on scanning. We believe that the association of parotid cysts and cervical adenopathy is another manifestation of AIDS or ARC and, when found on scanning, should alert the clinician to the probable underlying condition.

Two-dimensional echocardiography and indium 111-labelled platelet scintigraphy have proved helpful in the diagnosis of left intraventricular thrombosis. In this study, both methods were used to investigate the time-related changes undergone by such thrombi in 30 patients (26 with myocardial infarction, 4 with dilated cardiomyopathy) who presented with left intraventricular thrombosis diagnosed by echocardiography and systematically explored by indium scintigraphy. These 30 patients were divided into 2 groups depending on whether the initial scintigraphy was positive (group I, 19 patients) or negative (group II, 11 patients). The follow-up (mean 21.6 months) was clinical and paraclinical, with control echocardiography repeated at 1.5 and 8.5 months in both groups and control scintigraphy at 1.5 month in group I patients. At the 1.5 month echocardiography, the intraventricular thrombosis persisted in 14/16 examinations in group I patients and in only 2/10 examinations in group II patients (p less than 0.01). At the 1.5 month scintigraphy, performed in 16/19 group I patients, this examination had become negative in 8 cases, whereas the 2D-echocardiography remained positive. During the follow-up period 4 patients in group I had an embolic accident, as against none of the group II patients (p less than 0.01); 3 of these 4 patients had persistent uptake at control scintigraphy. At echocardiography, only a protrusion image seemed to be predictive, as it was present in 3 of 4 patients with embolic accident.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors compare three diagnostic-imaging methods (two-dimensional-echography, heart scans and indium-111 platelet scintigraphy) used in the detection of intracardiac thrombi in 82 patients. They attempt to define their respective diagnostic values in the presence of left ventricular and atrial thrombi.

Scintigraphy with Indium 111-labelled platelets was carried out in 62 patients (37 transient cerebral ischaemic accidents, 21 lower limb ischaemic episodes and 4 aortic aneurysms) to detect arterial thrombi. The results of this investigation were compared with the surgical findings and showed this to be a satisfactory method of detecting haematologically active thrombi.