Thomas S. Chen

Rise and fall of the Plummer‐Vinson syndrome

Three hypotheses have been proposed for the decreased incidence of Plummer‐Vinson disease: non‐existence, identity with inlet gastric mucosa of the oesophagus and disappearance of the predisposing condition(s). We examined these possibilities by reviewing our understanding of the syndrome. The early framers disagreed on the cause, but many thought it was a precursor for upper oesophageal carcinoma. Four explanations arose to account for the pathogenesis: iron deficiency; nutritional deficits; autoimmunity; and gastric lesion. We believe the decline in recognition paralleled the improve of dietary status and the treatment of sideropenic anaemia with inorganic iron salts.

ALCOHOLIC HEPATITIS, CIRRHOSIS, AND IMMUNOLOGIC REACTIVITY

Serial observations in over 40 alcoholics reveal there is a marked variation in the time required for transformation of alcoholic hepatitis t o cirrhosis. Some exhibited morphologic evidence of cirrhosis in less than a year, while others took as long as 12 years before its appearance. N o relationship could be established between the amount and type of alcoholic beverages and the dietary intake in patients who developed cirrhosis.’ These findings have led t o the consideration that altered immunologic reactivity might be responsible for the conversion of alcoholic hepatitis t o cirrhosis (FIGURE 1). This thesis is supported by the progressive shortening of the interval required for recurrence of alcoholic hepatitis with healing and subsequent resumption of alcoholism. An immunologic role in pathogenesis is also suggested by occasional hypersensitivity reactions following ingestion of alcoholic beverages; the ability of acetaldehyde t o depolymerize protein, which could then serve as an antigen; and the morphologic findings in alcoholic hepatitis, which simulate an Arthus-like reaction and/or delayed hypersensitivity reaction.

Intestinal autointoxication: a medical leitmotif.

The idea that putrefaction of the stools causes disease, i.e., intestinal autointoxication, originated with physicians in ancient Egypt. They believed that a putrefactive principle associated with feces was absorbed in to the general circulation, where it acted to produce fever and pus. This description of the materia peccans represented the earliest forerunner of our present notion of endotoxin and its effect. The ancient Greeks extended the concept of putrefaction to involve not only the residues of food, but also those of bile, phlegm, and blood, incorporating it into their humoral theory of disease. During the 19th century, the early biochemical and bacteriologic studies lent credence to the idea of ptomaine poisoning--that degradation of protein in the colon by anerobic bacteria generated toxic amines. Among the leading proponents of autointoxication was Metchnikoff, who hypothesized that intestinal toxins shortened lifespan. The toxic process, however, was reversed by the consumption of lactic acid-producing bacteria that changed the colonic microflora and prevented proteolysis. The next logical step in treatment followed in the early 20th century when surgeons, chief among them Sir W. Arbuthnot Lane, performed colectomy to cure intestinal autointoxication. By the 1920s, the medical doctrine fell into disrepute as scientific advanced failed to give support. However, the idea persists in the public mind, probably as an extension of the childhood habit of toilet training.

Rapid identification of smith-lemlip-opitz syndrome homozygotes and heterozygotes (carriers) by measurement of deficient 7-dehydrocholesterol-Δ7-reductase activity in fibroblasts☆

To extend the enzyme deficiency in Smith-Lemli-Opitz syndrome (SLOS) to extrahepatic tissues, 7-dehydrocholesterol-delta 7-reductase activity was measured in fibroblasts from 10 controls, five SLOS homozygotes, and five obligate heterozygotes. In cells grown almost to confluence in cholesterol-containing medium (4 mg/dL), the conversion of [1,2-3H]7-dehydrocholesterol to cholesterol (7-dehydrocholesterol-delta 7-reductase activity) was 3.8 times higher in control than in homozygote cells and 2.2 times higher than in heterozygote cells. After 24 hours exposure of the fibroblasts to cholesterol-deficient medium supplemented with lovastatin, 7-dehydrocholesterol-delta 7-reductase activity increased twofold in controls, but did not change significantly in either heterozygous or homozygous cells. In contrast, the activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and lathosterol 5-dehydrogenase, two key enzymes that precede 7-dehydrocholesterol-delta 7-reductase in the cholesterol biosynthetic pathway, and low-density lipoprotein (LDL) receptor-mediated binding were equal in control, homozygote, and heterozygote fibroblasts. Further, HMG-CoA reductase activity and LDL receptor-mediated binding increased after exposure of the cells to cholesterol-deficient medium. Fibroblast cholesterol concentrations were approximately equal, although homozygote cells contained 30 times more 7-dehydrocholesterol. Thus, markedly reduced 7-dehydrocholesterol-delta 7-reductase activity that cannot be upregulated after exposure of the cells to cholesterol-deficient medium is diagnostic for the biochemical defect in SLOS. Significantly reduced enzyme activity between the levels in controls and homozygotes without accumulation of 7-dehydrocholesterol in fibroblasts identified heterozygotes.

Elevated vitamin levels in colon adenocarcinoma as compared with metastatic liver adenocarcinoma from colon primary and normal adjacent tissue

Twenty‐four samples of colon adenocarcinoma removed at surgery and autopsy together with adjacent uninvaded normal colon from the same subjects were analyzed for vitamin B12 and B6, biopterin, nicotinate, riboflavin, pantothenate, thiamin, biotin, and folates. Nine specimens of metastatic liver adenocarcinoma from colon primary together with adjacent uninvaded normal liver were also analyzed for these same vitamins. Primary colon adenocarcinoma contains significantly (p < 0.001) more of the above vitamins than normal colon; 1.8‐ to 3.5‐fold higher concentrations of vitamins were found in this tumor. In contrast, vitamin B12 levels were almost two‐fold lower. Unlike colon tumor, metastatic liver adenocarcinoma from colon primary contained from 1.2‐ to 28‐fold lower vitamin concentration than normal liver tissue. The present findings suggest that those types of primary tumors with conspicuously high vitamin content needed for the enhanced growth and catalysis of tumor metabolism may be arrested with antivitamins targeted at metabolic sites other than those involved with nucleic acid synthesis.

Relationship of biopsy and final specimens in evaluation of tumor thickness in floor of mouth carcinoma

A number of studies have suggested that tumor thickness may be a valuable prognostic indicator in the evaluation of head and neck cancers. This study examined the relationship between tumor thickness measured in preliminary biopsy specimens with the final specimens obtained in 31 patients patients with floor of mouth epidermoid carcinoma. There was a significant statistical correlation between biopsy and final specimens. The Pearsons product‐moment correlation coefficient was 0.58, which corresponded to a significance level of P<.0005. The results of this study showed that those patients who had biopsies with a thickness less than or equal to 1 mm were likely to have final specimens with a thickness less than 2 mm. All patients with a thickness greater than 2 mm had a final specimen with a thickness greater than 3.5 mm. Modification of current biopsy techniques may result in values more predictive of final thickness measurements.

The accomplishments of Sir James Cantlie.

Sir James Cantlie succeeded in his diverse endeavours. A pioneer in first aid medicine in Britain, he wrote several important manuals on the topic. The interlude in Hong Kong set the stage for his role in Chinese history with his involvement with Sun Yat-Sen, the father of modern China, and in the establishment of the present Faculty of Medicine at the University of Hong Kong. The contact with tropical diseases sustained a career that included the founding of the current Royal Society of Tropical Medicine and Hygiene, and the extant Transactions of the Royal Society of Tropical Medicine and Hygiene. As a surgeon, he argued for a new concept of hepatic lobulation based on the vascular supply, and became recognized as the father of the surgical anatomy of the liver. The scope of Cantlies achievements is rivalled by few physicians, and his legacy remains with us to this day.

Studies of nucleic acid and collagen synthesis: current status in assessing liver repair.

Much progress has been made in delineating biochemical, physiologic and morpholigic events in liver regeneration and collagen synthesis. Pharmacologic agents have been purported to be helpful in facilitating repair and preventing fibrosis. Objective indices are now available to monitor their effectiveness in man.

Gastroenterology in ancient Egypt

Physicians in ancient Egypt devoted their care to disorders of individual organs. Notable among the specialties was gastroenterology, a subject matter that occupied a major portion of the surviving medical papyri. Although they did not name diseases as we know them, Pharaonic physicians described a host of gastroenterological symptoms for which an extensive array of therapeutics was prescribed. Their clinical accounts indicated an impressive knowledge of gastric and anorectal conditions. In their thinking on disease mechanism, the circulating materia peccans absorbed from feces represented a major cause of medical symptoms and disorders. This served as the rationale for the popular practice of self-purgation with enemas.

The healing Buddha.

The iconography of the healing Buddha embraces two healing traditions, symbolized by the healing stone lapis lazuli from Central Asia and by the myrobalan fruit from the ayurvedic medicine of ancient India. The first mention of the healing Buddha is in Buddhist texts of the first century BC, and the earliest extant icons date from the fourth century AD. This suggests the cult of the healing Buddha was a relatively late development in the history of Buddhism. Worshippers sought his help in alleviating spiritual, mental and physical suffering, as well as for medical cures. In China followers believed he was also a cosmic Buddha, to whom one appealed for longevity and protection from disasters. This form of faith-based healing remains vibrant in China, Japan and Tibet to this day.