Rising trends of gastric cancer and peptic ulcer in the 19th century.

BACKGROUND: The risk of dying from gastric cancer appears to have increased among consecutive generations born during the 19th century. AIM: To follow the time trends of hospitalization for gastric cancer and test whether they confirm such increase. METHODS: Inpatient records of the last two centuries from four hospitals in Scotland and three US hospitals were analysed. Proportional rates of hospitalization for gastric cancer, gastric ulcer and duodenal ulcer were calculated during consecutive 5-year periods. RESULTS: The data from all seven cities revealed strikingly similar patterns. No hospital admissions for gastric cancer or peptic ulcer were recorded prior to 1800. Hospital admissions for gastric cancer increased in an exponential fashion throughout the 19th and the beginning of the 20th century. In a majority of cities, the rise in hospitalization for gastric cancer preceded a similar rise in hospitalization for gastric ulcer. Hospitalization for these two latter diagnoses clearly preceded hospitalization for duodenal ulcer by 20-40 years. CONCLUSIONS: The occurrence of gastric cancer, gastric ulcer and duodenal ulcer markedly increased during the 19th century. Improvements in hygiene may have resulted in the decline of infections by other gastrointestinal organisms that had previously kept concomitant infection by Helicobacter pylori suppressed.

History of dyspepsia in Scotland. Admissions to the Edinburgh Royal Infirmary 1729-1830, doctoral theses 1726-1823, and contemporary British publications.

INTRODUCTION: The aim of the study was to assess whether the rise in the occurrence of dyspepsia in Scotland during the eighteenth century was a true epidemiologic phenomenon or just an increase in medical awareness. METHODS: Admissions for dyspepsia to the Edinburgh Royal Infirmary from 1729 until 1830 were analysed by consecutive five-year time periods. The titles of MD theses on dyspepsia from 1726 to 1823 were extracted from the Edinburgh University index. Monographs and articles on dyspepsia from Britain during the same time period were sought in the Catalogues of the US Surgeon-General's Library. RESULTS: During the eighteenth century, the annual number of dyspepsia patients admitted to the Edinburgh Royal Infirmary showed an extraordinary increase from none in 1730 to 900 per million population in 1760. About 4000 MD theses were presented to the Edinburgh University between 1726 and 1823. There were none on dyspepsia or gastritis between 1726 and 1749, after when it gradually started to rise. British publications on dyspepsia similarly appeared only in the 1790s and then rapidly increased. DISCUSSION: We suggest that the rise in MD theses and publications on dyspepsia were responses to a real increase in dyspepsia during the mid eighteenth century.

Three centuries of stomach symptoms in Scotland.

BACKGROUND: Stomach pain and discomfort have been reported since antiquity. AIM: To follow the time trends since the 18th century of dyspepsia, gastric ulcer, duodenal ulcer, and benign oesophageal disease to test when dyspepsia started to become a major clinical problem. METHODS: The annual in- and out-patient records of the last three centuries from the Scottish Royal Infirmaries of Edinburgh, Aberdeen, Glasgow and Dundee were analysed. In addition, dispensary attendances, clinicians' casebooks, students' notebooks and medical texts have been scrutinized for historic statistics of upper gastrointestinal disease. RESULTS: Dyspepsia was first recorded in the 1750s and increased markedly subsequently. Such dyspepsia persisted after gastric and duodenal ulcers appeared in the late 19th century and then declined again in the late 20th century. Non-ulcer dyspepsia has remained the commonest diagnosis made after endoscopy for stomach pain in the beginning of the 21st century. CONCLUSION: The current commonest diagnosis of stomach pain, dyspepsia dates from the mid-18th century. Any explanations of its causation need to consider this timing.

Alimentary diseases in the poor and middle class in London 1773-1815, and in New York poor 1797-1818.

BACKGROUND: Although dyspepsia has been described for thousands of years, few studies have analysed its incidence before the 19th century when peptic ulcer first became a major dyspepsia-producing disease. METHODS: The incidence of alimentary disease around 1800 was examined in three private practices for the fee-paying middle class and in five public dispensaries for the poor in London, as well as in one dispensary in New York. RESULTS: The proportions of attendances for alimentary disorders were identical, 16%, in each of the three groups. Diarrhoea and dysentery were twice as common in the London dispensary than in private practice, presumably because of poor sanitation. Dyspepsia showed a similar incidence in the London dispensary and private practice, but was only half as common in New York. Worms were three times more common in dispensary patients in New York than in London. The incidence of diarrhoea and dyspepsia indicated no significant time trends over 43 years. None of the alimentary causes of death showed peptic ulcer at necropsy, and both haematemesis and intestinal haemorrhage were rare. CONCLUSIONS: Around 1800, the infrequent deaths from alimentary conditions suggested that the ulcer epidemic had not yet started. Instead, it is probable that the dyspepsia was similar to the non-ulcer dyspepsia of today.

Hospital admissions for peptic ulcer and indigestion in London and New York in the 19th and early 20th centuries.

The occurrence of peptic ulcer increased rapidly in all Western countries from the 19th to the 20th century, attributed to a possible epidemic of Helicobacter pylori, a new pathogenic strain, or a change in host susceptibility. The early trends in hospital admissions for peptic ulcer and dyspepsia in London and New York during the 19th century are reviewed to test these hypotheses.

Period- and cohort-age contours of deaths from gastric and duodenal ulcer in New York 1804-1998.

OBJECTIVES: Mortality data of peptic ulcer are mostly national and limited to the 20th century. The New York City data from 1804 have therefore been examined by both year of death and year of birth (cohort analysis), to consider whether the increases and subsequent decreases in deaths from gastric, followed by duodenal ulcer, can be attributed to Helicobacter pylori. METHODS: The annual mortality reports of New York City described gastric ulcer from 1838 and duodenal ulcer from 1931. The age-specific death rates per 100,000 population were calculated in 10-yr periods both by year of death and by year of birth for each disease according to age and sex. RESULTS: For gastric ulcer the period-of-death-age contours from the 1850s to the 1990s showed an increase to a mid-19th century plateau, but the cohort-age contours revealed a peak mortality for those born in the 1870s. Women born between about 1770 and 1880 showed a faster increase in mortality. For duodenal ulcer the period of birth contours showed a decline from a peak for those born in the 1880s and 1890s, with no sex difference. CONCLUSIONS: This urban study with data regarding deaths from gastric ulcer registered from 1838 and in those born from the 1770s, revealed by cohort analysis a peak in the 1870s, and for duodenal ulcer in the 1880s, comparable to national data worldwide. These time changes in fatalities are compatible with a change in the environment of children born in these decades, as, for example infection by a pathogenic strain of H. pylori.

Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 Fab (abciximab): a possible mechanism for influencing restenosis.

OBJECTIVES: Brief intravenous administration of chimeric antibody c7E3 Fab during coronary angioplasty has been shown in some studies to provide long term protection against coronary events. Smooth muscle cell (SMC) adhesion and migration are key initial steps in the development of restenosis. The purpose of this study was to investigate the effect of c7E3 Fab on adhesion and migration of SMC to the extracellular matrix (ECM) proteins osteopontin (Opn) and vitronectin (Vn). METHODS: Adhesion of human vascular SMCs to ECM proteins was quantified using a CyQUANT assay kit. Migration of SMCs to Vn, Opn and PDGF was studied using a modified Boyden's chamber migration assay. Integrin expression was determined by immunoprecipitation. RESULTS: c7E3 Fab reduced SMC adhesion on Vn and Opn to 69.2+/-3.3% (P<0.001) and 52.5+/-4.8% (P<0.001) respectively, compared to adhesion without antibody present. This reduction was the same as that for anti-alpha(v)beta(3) integrin antibody LM609 (P=0.5). The combination of anti-alpha(v)beta(5) integrin antibody and c7E3 Fab had a greater effect than either antibody alone (P<0.001). c7E3 Fab reduced SMC migration to Vn and Opn to 51.6+/-8.9% (P<0.001) and 20.3+/-6.1% (P<0.001) respectively, compared to migration in the absence of antibodies. Again, similar results were seen with LM609. PDGF-induced SMC migration was also inhibited by c7E3 Fab (P=0.004) and LM609 (P=0.001), but to much less an extent. The migration SMCs from a culture found not to express the alpha(v)beta(3) integrin was unaffected by these antibodies, strengthening the argument that c7E3 Fab inhibits SMC function via this integrin. CONCLUSIONS: c7E3 Fab inhibits the adhesion and migration of SMCs via the alpha(v)beta(3) integrin. The inhibition, however, is partial, and varied depending on type of ECM protein and alpha(v)beta(3) integrin expression. Some of the clinical benefits of c7E3 Fab may be due to its effect on SMCs.

In vitro evaluation of c7E3-Fab (ReoPro) eluting polymer-coated coronary stents.

OBJECTIVE: Stent thrombosis and in-stent restenosis remain problematic in certain patient sub-groups. c7E3-Fab (ReoPro, abciximab) inhibits the platelet glycoprotein IIb/IIIa receptor as well as the smooth muscle cell alpha(v)beta3 receptor, and thus may influence both processes, especially if high local concentrations could be achieved. We have studied the adsorption and elution characteristics of c7E3-Fab on commercially available polymer-coated stents. We have also investigated the effect of such antibody binding on platelet deposition in vitro, and on antibody deposition into ex vivo human saphenous vein wall to assess whether such stents may influence stent thrombosis and restenosis. METHODS AND RESULTS: Adsorption was measured using a radioisotope technique after immersing segments of polymer-coated stents in c7E3-Fab solutions. Uptake was dependent on antibody concentration and duration of immersion of wire in the solution. After 22 h (at 5 mg ml(-1)), 1146+/-101 ng cm(-1) wire was adsorbed. In an in vitro perfusion circuit, the antibody eluted slowly, with 53% remaining after 12 days washing. To determine the value that such stents might have in clinical practise, adsorption to balloon-mounted stents was assessed at room temperature, using commercially available c7E3-Fab (2 mg ml(-1)). Efficacy of eluting c7E3-Fab was determined by measuring deposition of 111-Indium platelets. Immersing stents in c7E3-Fab for 20 min inhibited platelet deposition by 82.3% compared to controls (P=0.018). Deployment of treated stents in ex vivo saphenous vein resulted in the deposition of c7E3-Fab in the intima and media. CONCLUSIONS: c7E3-Fab can be passively adsorbed onto polymer-coated stents. It elutes slowly and in a predictable manner, significantly inhibiting platelet deposition in vitro. These studies pave the way to developing stent-based delivery of a potent anti-platelet agent that may additionally affect smooth muscle cell activity.

Inflammatory bowel disease up to 1932.

Inflammatory bowel diseases have been a major interest of generations of Mount Sinai Hospital gastroenterologists. Although clinical descriptions of diarrhea with or without blood go back thousands of years, clear distinctions between enteritis and ulcerative colitis were possible only in the 19th century. At that time, many case reports were published of, in retrospect, classical regional enteritis. The term "ulcerative colitis" dates from 1888; the introduction of the electric sigmoidoscope soon after made it possible to make proper diagnosis of ulcerative colitis and distinguish it from infective dysentery, membranous mucous or catarrhal colitis, and nervous diarrhea. Doctors at The Mount Sinai Hospital adopted this diagnostic approach in the 1870s and 1880s, and were particularly interested in patients with tuberculosis-like ileocecal disease without tubercle bacilli. Articles were written by Weiner in 1914, Moschcowitz and Wilensky in 1923 and 1927, and Goldfarb and Suissman in 1931. Dr. A.A. Berg, in 1925, encouraged his assistant Leon Ginzburg to conduct a study of the inflammatory granulomatous diseases of the bowel, when Ginzburg and Gordon Oppenheimer were working in Dr. Paul Klemperer's laboratory. Initial reports came in 1927 and 1928, but Ginzburg and Oppenheimer "in conjunction with Dr. Burrill B. Crohn" presented a definitive paper, "Non-specific Granulomata of the Intestine," on May 2, 1932, to the American Gastro-Enterological Association. On May 13, 1932, Dr. Crohn presented a paper on "Terminal Ileitis" to the American Medical Association; this was published later that year with the title "Regional Ileitis: A Pathologic and Chronic Entity," under the authorship of Crohn, Ginzburg and Oppenheimer.

Inhibition of platelet thrombosis using an activated protein C-loaded stent: in vitro and in vivo results.

In high-risk and complicated coronary intervention, the risk of acute closure is unpredictable. Thrombus and platelet deposition at the intervention site may also have further effects on subsequent restenosis. In vivo infusion of activated protein C has previously been shown to achieve potent anticoagulation without any haemostatic side effects. We now evaluated the in vitro and in vivo efficacy of polymer-coated coronary stents loaded with purified rabbit Activated Protein C (APC). By measuring 125I-fibrinogen/fibrin deposition APC-loaded stent-wires were antithrombotic compared to albumin-loaded, inhibited-APC-loaded, plain polymer-coated and stainless steel stent-wires. In a balloon injury rabbit iliac artery model, APC-loaded stents did not occlude (0/14) compared to plain stents (9/15) and BSA-loaded stents (2/4). Relative 111In-labelled platelet deposition showed a similarly significant degree of inhibition. In conclusion, APC-loading could render stents significantly less thrombotic. Whether an effective antithrombogenic stent like this effectively reduces restenosis rates warrants further evaluation.

The Mount Sinai Hospital--a brief history.

In 1852, The Jews Hospital was founded for the increasing number of Jews in New York. It opened in 1855 with 45 beds on West 28th Street; 92% of the patients were indigent. In 1864, the hospital formally became nonsectarian and, in 1866, changed its name to The Mount Sinai Hospital. The medical staff was primarily Jewish, because until relatively recently, it was difficult for Jewish doctors to obtain postgraduate training or specialist posts at major New York hospitals. As the Jewish population moved uptown, so did The Mount Sinai Hospital: in 1870 to 66th Street, and in 1904 to 100th Street, with 456 beds, growing with new buildings and services to the current 1100 beds, 50,000 discharges, 400,000 inpatient days and 300,000 outpatient visits each year. Services increasingly became specialized, and then subspecialized. Key innovations included the choice of interns by competitive examination (1872), an advisory Medical Board (1872), the Nurse Training School (1881), the library (1883), the Alumni Association (1896), a professional medical hospital administrator (1903), research laboratories (1904), clinicopathological conferences (1905), the Social Services Department (1906), postgraduate teaching programs (1923), full-time chiefs of clinical services (1944), the dedication of the Mount Sinai School of Medicine (1968), and the merger in 1998 into the Mount Sinai-New York University Medical Center.

Gastroenterology and hepatology as subspecialties.

Gastroenterology grew as a subspecialty in Germany in the 19th century. In the 1880s and 1890s, Austrian and German clinics were attended by American physicians who, on returning to the U.S., founded the American Gastroenterological Association in 1897. The creation of a subspecialty board, however, had to wait until 1941. At The Mount Sinai Hospital, Dr. A.A. Berg was appointed Surgeon in 1899. His practice focused on the alimentary tract, which in 1910 became one of the four surgical specialties. In 1914, further subdivision led to the stomach and duodenum becoming additional specialties. In 1917, wards were endowed for Dr. Berg's specialty. The first Mount Sinai physician to have an interest in gastroenterology was Morris Manges, but the first to limit his practice to gastroenterology was Dr. Edward Aronson, for whom a specialist outpatient division was formed in 1913. Aronson died in 1922 and was succeeded by Dr. Burrill Crohn, who was followed in 1934 by Dr. Asher Winkelstein; all three collaborated closely with the surgeons, physiologists and biochemists. In 1958, Dr. Henry Janowitz became chief of the Division of Gastroenterology; he was succeeded in 1983 by Dr. David Sachar, who was followed in 1999 by his associate Dr. Steven Itzkowitz. In 1958 Dr. Fenton Schaffner became chief of the Division of Hepatology (now headed by Dr. Paul Berk), and in 1979 Dr. LeLeiko became chief of Pediatric Gastroenterology.

Gastroenterology and hepatology--the diagnostic data.

The Annual Reports of the Mount Sinai Hospital from the 1850s, and the Mount Sinai Hospital Reports for 1897-1906, make it possible to trace the discharges of gastroenterological inpatients, and (for a few years) of outpatients. Fully computerized diagnostic data have only been available since 1986. In the 19th century, about 20% of the outpatients had digestive disorders, the commonest of which were gastralgia/gastritis/dyspepsia, gastroenteritis, oropharyngeal complaints and constipation. A similar proportion of inpatients had digestive diagnoses, but the four disorders listed above decreased markedly in the second half of the 19th century, so that by the turn of the century the commonest diseases were typhlitis (appendicitis), hemorrhoids and other anal problems. By the 1990s, digestive diseases accounted for only 5% of total admissions, hepatobiliary diagnoses being the commonest group. Some cancers such as gastric and esophageal showed little change, while colorectal increased markedly. Some newly recognized diseases, such as peptic ulcer, waxed and then waned, while colitis and regional enteritis came and have continued to increase. Other new diagnoses, such as autointoxication and visceroptosis, flashed into prominence and then disappeared totally, presumably because they were nondiseases.

Gastric secretion.

The European gastric test meal was widely used in The Mount Sinai Hospital in the 1890s and early 1900s, but was then abandoned diagnostically after the introduction of gastroscopy and radiology. The fundamental methodological advances of Franklin Hollander led to his quantitative formulation of the ionic concentrations of the gastric acid parietal and nonparietal components, followed by his insulin test for completeness of vagotomy.