Autostimulation of growth by human myelogenous leukemia cells (HL-60)

We have studied the effects of medium conditioned by the human progranulocytic leukemia cell line, HL-60, on the subsequent growth of new inocula of HL-60 cells. When HL-60 cells were cultured at high cell density, optimal growth rate occurred in liquid suspension and confluent colony growth was observed in viscous medium without the addition of conditioned medium. However, when cells were cultured at lower cell density, growth rate was reduced and colony growth was nil unless conditioned medium from HL-60 culture was added. All HL-60 populations studied, including the earliest available passage, 9, both elaborated and responded to HL-60 CM. HL-60 CM did not stimulate normal human or mouse granulocyte-monocyte colony-forming cell (CFU-GM) growth. Conditioned media from other human cell lines varied in the ability to stimulate HL-60 cell and CFU-GM proliferation. Some, such as GCT CM, stimulated both HL-60 cells and normal CFU-GM, whereas others, like HL-60 CM, stimulated only HL-60 growth. The majority of cell line CMs tested did not stimulate either HL-60 or CFU-GM. Chromatography of HL-60 CM on Ultrogel AcA54 showed a single peak of HL-60 stimulating activity of apparent molecular weight 13,000. The ability of HL-60 cells to elaborate this activity provides a possible explanation for their proliferation at higher cell densities. Autostimulation may prove to be important in the high growth potential of other cell populations that undergo unrepressed proliferation.     

Acanthosis nigricans and hypovitaminosis A. Response to topical vitamin A acid

The pathogenetic mechanisms in acanthosis nigricans are not well known. Hirschowitz et al. (1971) described a new syndrome which included complete nerve deafness, progressive peripheral sensory nerve demyelinization, loss of gastric antral motility, multiple diverticula of ileum and lower jejunum, steatorrhea and unusually extensive acanthosis nigricans. Dramatic clinical and histological response of the dermatosis to topical vitamin A acid treatment led to search and demonstration of severe hypovitaminosis A. The trifluoroacetic acid method of Neeld & Pearson (1963), repeatedly used with serum samples, either failed to detect β-carotene and/or vitamin A or showed levels below the normal range. These findings indicate that vitamin A deficiency may be a factor in the pathogenesis of acanthosis nigricans.     

Studies on the epidemiology of neuropsychiatric disorders among the rural population of the province of Khuzestan,Iran

Summary The authors undertook a census study of five small rural villages from the Dez Pilot Irrigation Area of the Province of Khuzestan in south-western Iran which had been hardly touched yet by the on-going development program. From the total population of 614 souls all children below the age of six years were eliminated, these being 129 in number, leaving 485 persons. Three could not be examined because of absence or illness, leaving 482 or 99.4% of the intended survey population. All were given two short intelligence tests (mental arithmetic and block design), the 2 Test of H.Zulliger and a brief questionnaire by Persian lay assistants whom the authors themselves trained. The examiners were required to give a commonsense judgment of their subjects' mental health. The authors observed and supervised all testing, interrogated the subjects and informants where this seemed required and evaluated the tests concurrently. All subjects who seemed suspicious of neuropsychiatric pathology were then given an individual clinical examination. Seventy-two cases were found with apparently significant psychiatric disturbances. Among them there were one functional psychosis, no acute symptomatic psychosis, 15 subchronic and chronic symptomatic psychoses or disorders, 42 psychoreactive disorders and 14 constitutional disorders. Of the 72 psychiatrically disturbed subjects, 37 were mildly, 30 moderately and 5 severely affected. Eleven subjects presented significant neurological or mixed neuropsychiatric disorders.Comparison of the results with those of a similar survey performed in the Marvdasht District of the Province of Fars, Iran, indicates that more prolonged, intensive and individual exploration of subjects showing any suspicion of psychopathology leads to an increase in the number of milder cases identified without changing significantly the number of moderate and severe cases.

---

Zusammenfassung Die Verfasser unternahmen eine neuropsychiatrische Erhebung in fünf kleinen ländlichen Dörfern der Dez Pilot: Irrigation Area der Provinz Chuzestan, Iran, welche von dem fortschreitenden Entwicklungsprogramm noch kaum erfaßt worden waren. Aus der Gesamtbevölkerung von 614 Seelen wurden alle Kinder unter sechs Jahren, 129 an der Zahl, ausgeschieden, wonach 485 Personen übrig blieben. Davon konnten drei wegen Abwesenheit oder Krankheit nicht untersucht werden. Übrig blieben 482, d. h. 99,4 v. H. der vorgesehenen Gruppe. Allen diesen wurden zwei kurze Intelligenzprüfungen (Kopfrechnen und Würfeltest), der Z-Test nach H.Zulliger und ein kurzer Fragebogen durch iranische Mitarbeiter (Laien) gegeben, welche die Verfasser selbst zu diesem Zweck ausgebildet hatten. Diese Untersucher sollten ferner bei jedem Untersuchten ein Laienurteil über dessen seelische Gesundheit, bzw. Krankheit abgeben. Die Verfasser beobachteten und überwachten alle Prüfungen, befragten Versuchspersonen und Auskunftspersonen, wo dies angebracht schien und werteten die Tests fortlaufend aus. Alle Versuchspersonen, die danach irgendwie verdächtig auf neuropsychiatrische Pathologie schienen, wurden dann einzeln klinisch untersucht. Man spürte auf diese Weise 72 Fälle mit nennenswerten psychiatrischen Störungen auf. Darunter fand man eine funktionelle Psychose, keine akute symptomatische Psychose, 15 subchronische oder chronische symptomatische Psychosen oder Störungen, 42 psychoreaktive Störungen und 14 konstitutionelle Störungen. Von den 72 psychiatrisch abwegigen Personen waren 37 in leichtem, 30 in mittlerem und 5 in schwerem Grad gestört. Elf Personen boten nennenswerte neurologische oder gemischt neuropsychiatrische Störungen.Der Vergleich der Befunde mit denjenigen einer ähnlichen Erhebung im Marwdascht-Bezirk der Provinz Fars, Iran, zeigt, daß eine längere, intensive und individuelle Abklärung von Personen, die auf Psychopathologie verdächtig scheinen, zur Erhöhung der Anzahl der in leichtem Grad gestörten und also festgestellten Personen führt, ohne die Anzahl der in mittlerem und schwerem Grad Gestörten merklich zu beeinflussen.

---

Résumé Les auteurs ont entrepris une enquête, à la fois neurologique et psychiatrique, dans cinq petites agglomérations rurales situées dans la «Dez Pilot Irrigation Area» de la province iranaise du Chuzestan. Le vaste plan de développement, actuellement en plein essor en Iran, n'avait, jusqu'à présent, que très peu touché cette région éloignée.La population globale des cinq villages en question comptait 614 personnes. 129 enfants, âgés de moins de six ans, furent éliminés de l'enquête. Des 485 personnes restantes, trois ne purent être examinées par suite de maladie. Les 482 sujets soumis à l'investigation représentèrent donc 99,4% du groupe envisagé.Chaque individu fut soumis à une petite batterie de tests, comportant deux petites épreuves d'intelligence (calcul mental et cubes) ainsi que le test «Z d'après H.Zulliger. Ensuite, des collaborateurs laiques iranais questionnèrent les sujets selon un questionnaire élaboré par les auteurs. Ces collaborateurs eurent également pour tâche de donner leur avis nonspécialisé sur l'état de santé ou de maladie mentale des personnes questionnées.Les auteurs observèrent et surveillèrent toutes les épreuves et tests décrits plus haut et questionnèrent, à leur tour, les personnes soumises à l'enquête ainsi que — lorsque le besoin s'en imposa — toute personne pouvant fournir des renseignements complémentaires. Les auteurs interprétèrent également les tests dans l'ordre de leur finition.Toute personne, ayant été ainsi trouvée suspecte d'affection neuropsychiatrique, fut ensuite soumise à un examen clinique individuel et approfondi.De cette manière, on put dépister 72 cas présentant des troubles psychiatriques significatifs. Parmi ces cas, il fut trouvé une psychose fonctionnelle, par contre pas de psychoses symptomatiques aiguës, 15 cas de psychose ou d'altération symptomatique chronique ou subchronique, 42 cas de troubles psychoréactifs et 14 altérations constitutionelles. Des 72 cas manifestement psychiatriques, 37 furent légèrement atteints, 30 moyennement et 5 cas furent gravement atteints. 11 personnes présentèrent des troubles neurologiques significatifs ou des images mixtes de troubles neuropsychiatriques.En comparant les résultats de la présente enquête avec ceux, entrepris lors d'une investigation dans la région de Marwdascht (province iranaise des Fars), il appraît que l'exploration prolongée, intensive et individuelle de sujets, suspects de maladie mentale, donne lieu à une augmentation du nombre des cas frustes, sans pour autant influencer notablement le nombre de troubles psychiatriques de gravité moyenne ou intense.

---

---

Slightly expanded version of a lecture held at the Max Planck Institute for Psychiatry in Munich, June 30, 1967.     

Simulation and its role in medical education

Medical education is increasingly laying emphasis on a curriculum based on cognitive, psychomotor, and affective domains of learning which were originally proposed nearly 50 years ago. These reforms are framed around best standards of care, error management and patient safety, patient autonomy, and resource allocation. There is a worldwide shift in the method of medical education towards experiential (‘hands-on’) medical learning; however, applying this concept to real patients is less acceptable to society and is subject to legal and ethical issues.     

Inhibition of Secretory Phospholipase A2 in Patients with Acute Coronary Syndromes: Rationale and Design of the Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16) Trial

Background  

The action of secretory phospholipase A₂ (sPLA₂) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events that is associated with biomarkers of inflammation, including sPLA₂. The Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16, NCT01130246) tests the hypothesis that varespladib methyl, an inhibitor of several sPLA₂ isoforms with a causal role in atherosclerosis, reduces cardiovascular risk among patients with acute coronary syndromes.