Hans Popper

Hypertrophic, hypoactive smooth endoplasmic reticulum: a sensitive indicator of hepatotoxicity exemplified by dieldrin.

Rats with hypertrophic smooth endoplasmic reticulum (ER) and increased activities of the drug-handling enzymes induced by dieldrin were stressed with larger doses of the pesticide. The activity of the drug-handling enzymes was thus reduced, but liver weight, smooth ER, and P-450 hemoprotein remained elevated. While no changes were apparent by light microscopy, the hypertrophic, hypoactive smooth ER was recognized as tight clusters of tubular membranes associated with abnormalities of the mitochondrial membrane. Similar but not identical morphologic changes were noted in human liver diseases associated with hepatic insufficiency. Hypertrophic, hypoactive smooth ER may indicate transition from adaptation of injury, and can be used as a sensitive parameter of toxicity.

RELATION BETWEEN AUSTRALIA ANTIGEN AND AUTOIMMUNE HEPATITIS

Abstract It is postulated that the Australia-antigen particle of hepatitis type B represents an infectious agent different from viruses described so far. It is assumed that it consists of a very small amount of R.N.A.-enzyme complex (virion) with an amount of host protein far in excess of the protein coat of most other viruses. These host proteins include various pre-existing structures of the liver cell. Acute type-B viral hepatitis is regarded as a restricted immunological response to the proteins in the complete B-antigen particle. It is presumed that, if there is a hepatitic antecedent of chronic liver disease, it will be B-antigen-positive hepatitis. Such chronic liver disease may be the result of one of two processes: (1) continued restricted immune reactions to the virion or, more probably, to the protein of the whole B-antigen particle, with infectivity which persists because of the presence of the virion and with a characteristic distribution of antigen in other organs (polyarthritis and polyarteritis); (2) florid and per sisting autoimmune reaction to specific host components of broken-down B-antigen particles, occurring predominantly in females, in the absence of the virion and of infectivity, and with great variation in the clinical manifestations, depending on the character of the antigenic components of the particle fragment and the organ localisation of immune complexes. The nature of the autoimmunogen in the particle may determine whether a chronic aggressive hepatitis, primary biliary cirrhosis, or an overlapping syndrome develops.

Pathology of angiosarcoma of the liver among vinyl chloride-polyvinyl chloride workers.

We described the histologic features of 13 hepatic angiosarcomas which developed in workers engaged in the polymerization of vinyl chloride to polyvinyl chloride. Although the histologic features varied considerably in different portions of the angiosarcoma in the same liver and in the angiosarcomas of the liver from different patients, many features were similar such as sinusoidal, papillary, and cavernous growth patterns coincident with the precursor lesions of proliferation and atypia of sinusoidal lining cells.

Injury and Repair of Liver Cells

Alterations in hepatocytes, progressing to necrosis, are the morphologic basis for the main clinical manifestations and aberrations in hepatic test results in acute and chronic liver disease. The light-microscopic manifestations of hepatocellular injury, the mechanisms of necrosis, the light-microscopic features of repair and regeneration, and the applications of histologic alterations to the management and prognosis of liver disease are reviewed.

Evolution of thorotrast-induced hepatic angiosarcomas.

Abstract A histological review of 25 cases of thorotrast-induced angiosarcoma revealed characteristic antecedent or precursor changes which are similar to previously described changes present in hepatic angiosarcoma secondary to vinyl chloride, arsenicals, or of unknown etiology. The antecedent or precursor change consists of areas with simultaneous activation of both the hepatocytes and sinusoidal cells and associated lesions in the sinusoidal and perisinusoidal spaces. The hepatic cell plates surrounding these areas are compressed with subsequent development of fibrous septa at the interface between the areas of mixed hyperplasia and the areas of compression. In these multiple areas multicentric angiosarcomas develop in close approximation to the portal tracts but not to the thorotrast deposits.

A new curriculum.

The greatest challenge to a newly developing medical school is the planning of the curriculum. This is an optimal time because the vested interests of the faculty are not yet established and the opportunity for change diminishes fast as the school is organized. Alterations of the curriculum in an old established school are traumatic. Developing schools must grasp this ephemeral opportunity to experiment with curriculum to fulfill dreams of the founding group. However, the realities of medical education often force great innovations in the initial scheme into a surprising conformity with older patterns with much of the variation being in semantics rather than in operation. Under these circumstances I understand the decision of the organizing committee of this conference to select a speaker on new curriculum, who may be rich in dreams but poor in experience and who out of naivet6, would dare to present schemes which have not yet met the test of students and faculty resistance. The philosophy of a new curriculum is to take into account the newer trends and goals in health care and life sciences as they affect medical education.

NEW OBJECTIVES IN MEDICAL EDUCATION

Medical education of today must be geared to the medical needs of tomorrow. New objectives of medical education thus depend on the prediction of these needs which are dictated by the new developments in medicine as well as by the changing structure of society. Such predictions are hazardous and highly subjective but they must be attempted particularly in the planning for a newly developing medical school. Conscious of the hazard of subjective bias and admitting other limitations, I shall attempt nevertheless to predict the course of future developments and to describe the means of meeting the consequent needs.