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Using the unique data resources of the Rochester Epidemiology Project, a community-based study of clinically diagnosed sarcoidosis was conducted. In this population-based study, the 75 Rochester, Minnesota, residents with sarcoidosis initially diagnosed between 1946 and 1975 (incidence cohort) were followed through their comprehensive medical records in the community to January 1, 1982. The age- and sex-adjusted incidence of sarcoidosis was 6.1 per 100,000 person-years. The age-adjusted incidence of sarcoidosis was similar in males (5.9) and females (6.3), with a peak incidence in males 30 to 39 years old (18.7) and in females 40 to 49 years old (15.6). A secular increase in sarcoidosis incidence was noted in the period 1946-1975 for females, with a marked increase in the number and percentage of biopsy-documented cases. Seasonal variation in sarcoidosis incidence was minimal, with a seasonal peak of 31% of the Rochester cases being diagnosed during the spring (March-May). Survival, compared with that of the North Central United States, was unimpaired in this sarcoidosis incidence cohort.

Acetylcholine receptor (AChR) binding and AChR modulating antibodies were found with approximately the same frequency (86%) in 349 patients with myasthenia gravis (MG). However, the total yield of positive serological results was significantly improved (90%) by assaying AChR modulating antibodies when AChR binding antibodies were not detected, because in 27 patients (8%) only one of the two tests was positive. The immunoprecipitation test for AChR blocking antibodies yielded fewer positive results (52%), but there was a significant correlation between the degree of AChR blockade and generalization of muscle weakness. In no patient was this the only positive test, because the test for AChR modulating antibodies in this study detected both AChR blocking and modulating antibodies. Human muscle AChR was used as antigen in all tests. False positive results were rare and were attributed to unexplained antibodies to 125I-alpha-Bgt (AChR binding antibody assay) and recent general anesthesia using muscle relaxants (AChR blocking and AChR modulating antibody assays). Unexplained positive results, documented previously in 5% of patients with the Lambert-Eaton myasthenic syndrome and amyotrophic lateral sclerosis (ALS), were found in this study in two of 22 patients with ALS, but in none of 427 patients with miscellaneous neurological diseases. Patients with severe generalized MG and/or thymoma tended to have higher titers of AChR binding antibodies and greater AChR modulating antibody activity. However, some patients with severe muscle weakness had low titers of antibodies, and some patients in remission or with only ocular manifestations had high titers. These seemingly paradoxical results reflect heterogeneity in the specificities, affinities, and isotypes of anti-AChR antibodies. To effect pathogenicity, antibodies must have access in vivo to extracellular antigenic sites on the AChR. One would anticipate that antibodies with greatest pathophysiological potential would be of an IgG with greatest pathophysiological potential would be of an IgG subclass that activates complement, or of a specificity that competes for acetylcholine's binding site on the receptor or readily cross-links two AChR molecules to trigger receptor modulation (e.g., by binding to sites on the duplicated alpha-subunit). In patients with suspected MG who lack serological evidence of anti-AChR antibodies, motor endplate biopsy is required for microelectrophysiological, immunochemical, and ultrastructural studies to establish with certainty whether or not the condition is acquired MG.

Complete follow-up data were obtained from 229 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1979 and 1982 (mean follow-up 14 months, range 6 to 37). Single-vessel disease was present in 143 and multivessel disease in 86. PTCA was successful in 153 patients (67%). Failure was followed initially by bypass surgery in 59 and by continued medical therapy in 17. After successful PTCA, 90% of patients were improved subjectively and 74% were asymptomatic at follow-up. After unsuccessful PTCA but prompt bypass, 90% were improved subjectively and 85% were asymptomatic. Among the 229 patients, 39 (17%) required an additional intervention because of angina during follow-up; 15 of these had repeat PTCA and 18 had bypass surgery. Among patients with successful PTCA, revascularization was complete in 77% and partial in 23%. The completeness of revascularization with PTCA had a significant impact on follow-up. The follow-up data of patients with successful single-vessel PTCA and of those with multivessel disease with complete revascularization were similar. When the patients with complete revascularization were compared with those with multivessel disease but incomplete revascularization, the follow-up data were characterized by a higher incidence of angina or need for bypass surgery in the latter group (63%) than in the former group (29%); those with incomplete revascularization also had a significantly reduced event-free survival.

Factors that influence the effect of coronary artery bypass graft surgery (CABG) on employment were examined in 1427 2-year survivors from entry into the nonrandomized Mayo Clinic portion of the National Heart, Lung, and Blood Institute's prospective Coronary Artery Surgery Study. Five hundred seventy-nine patients (41%) were treated medically, 769 (54%) were treated surgically and 79 (5%) were initially treated medically but later had CABG. All groups were similar at entry with respect to age and percent working, retired or quitting work for cardiac reasons. There was a similar decline in employment from entry to 2 years in all three groups. The number who quit work for cardiac reasons was twice the number of previously disabled workers who returned to work with all three modes of therapy. Univariate and multivariate analyses were used to test the independent prognostic values of a number of variables for subsequent employment in the largest homogeneous surgical subset--496 nonretired males. Postoperative angina was the most powerful factor reducing postoperative employment. Postoperative employment was also lower if the patient was not working before surgery, was a laborer, or older than age 55 years (all p less than 0.01). Although the level of nonwork physical activity was generally increased after CABG, there was no relationship between physical activity and employment. This study confirms that employment declines after CABG, but three of the four most powerful prognostic variables were not related to surgery.

Coronary arteriography in 300 patients within one year of onset of symptoms of coronary arterial disease revealed already severe anatomical coronary disease in three patient groups: those with angina pectoris alone (164 patients), with subendocardial myocardial infarction (63 patients), and with transmural myocardial infarction (73 patients). The number of vessels diseased (larger than or equal to 50% obstruction), distribution of obstruction, and degree of stenosis were similar in the three groups. However, total occlusion of at least one artery was much more common in transmural myocardial infarction and in subendocardial myocardial infarction with elevation of enzyme levels. We suggest that such occlusions occurred at the time of the infarction. Similarities in coronary anatomy between patient subgroups with angina (on exercise or at rest and nocturnal) indicate that factors other than coronary anatomy intervene in precipitating the different types of angina. Vessel disease was not related to smoking, hyperlipidaemia, or hypertension but coronary disease was manifest earlier in life in smokers or those with hyperlipidaemia.

To determine the usefulness of the cold pressor test as a predictor of hypertension, we compared the blood pressure recordings available from 142 patients in 1979 with readings obtained during performance of two cold pressor tests, the first in 1934 when these subjects were children, and the second in 1961. Forty-eight subjects were hyperreactors to the tests in either 1934 or 1961, and 94 were normoreactors. At last follow-up, blood pressures in 14 of the hyperreactors were between 140 and 160 mm Hg systolic or 90 and 100 mm Hg diastolic (Stratum 1) and in 20 exceeded 160 mm Hg systolic or 100 mm Hg diastolic (Stratum 2). Ten normoreactors had casual blood pressures in Stratum 1 and eight in Stratum 2. Hypertension had thus occurred in 71% of the hyperreactors and 19% of the normoreactors. Fifteen hyperreactors were receiving antihypertensive therapy, and this reduced the severity of the casual blood pressure elevation in most patients to Stratum 1. Antihypertensive therapy had been started in three normoreactors. The duration of follow-up, 45 years, and the mean age at follow-up, almost 57 years, were greater in this study than in any previously reported study. Early hyperreactivity was related to future hypertension in enough subjects to suggest that an abnormal response to an external cold stimulus may be useful as an indicator of future hypertension.

This population study describes the experience with primary intracerebral hemorrhage (PIH) in residents of Rochester, MN, for the 32-year period from 1945 through 1976. The average annual age-adjusted incidence rate for PIH was 12.1 per 100,000 population, and the incidence for all cases of spontaneous intracerebral hemorrhage was 15.2 per 100,000. The PIH rates were higher for males than for females, and they increased steadily with age. When patients on long-term anticoagulant therapy were excluded, there was a steady decrease in the average annual age-adjusted incidence rate for PIH in each succeeding 8-year interval since 1945. Prehemorrhage hypertension, present overall in 89% of patients, was much more frequent and severe in the earlier years of the study. The frequency and severity of prehemorrhage hypertension also varied inversely with age in the population with PIH. The median age at the onset of PIH increased from 65 years for the period 1945 through 1952 to 71 years for 1969 through 1976.

The incidence and prevalence rates of connective tissue disease syndromes in Rochester, Minnesota, from 1950 through 1979 are reported. The incidence of definite systemic lupus erythematosus (SLE) has not increased since 1960. The incidence of SLE in the elderly population was higher than that in previous reports. Rates of SLE and discoid lupus erythematosus were approximately equal. Other diagnoses (in decreasing order of frequency) were suspected lupus erythematosus, scleroderma, drug-induced lupus, and overlapping connective tissue disease syndromes. The 10-year survival of patients with definite SLE was decreased, and the survival of patients with suspected SLE was the same as that of the general population.

Cigarette smoking or a strong family history of coronary disease was present in 46 of 50 symptomatic patients with coronary artery disease who were younger than 50 years of age. We recorded a shortened platelet survival half-life (less than 92 hours) with 51Cr in 60% of these patients, in 56% of apparently normal persons of the same age who smoked or had a strong family history of coronary disease, and in only 14% of normal persons who did not smoke and had no family history (p less than 0.01). Lengthening of the shortened platelet survival toward normal occurred in coronary patients given dipyridamole plus aspirin and in apparently normal smokers who discontinued smoking (p less than 0.01). The study suggests a possible relationship among cigarette smoking, strong family history of coronary disease and platelet activation in the process of coronary atherogenesis in the young adult.

Summary: Standardized mortality ratios (SMR) were determined for a cohort of patients with first diagnosis of epilepsy as residents of Rochester, Minnesota, between 1935 and 1974. SMR for the total group was 2.3 through 29 years of follow-up. SMR was lower for those with idiopathic epilepsy, although still significantly increased from expected. Several groups with idiopathic epilepsy did not have significantly elevated mortality rates. This included patients with absence seizures, partial and complex seizures, first diagnosis of epilepsy between ages 1 and 19, or patients who were female. Patients with febrile convulsions did not demonstrate alterations in expected mortality. Patients with single idiopathic generalized seizures did have an increase in mortality. For the group as a whole, as well as all idiopathic cases, the most significant increase in SMR occurred in the first 10 years following diagnosis. Interval SMRs were also significantly increased between 25 and 29 years following diagnosis. This suggests either a late effect associated with predisposition for seizures, an effect related to the chronic medication used for therapy, or a combination of the two. Patients experiencing remission of seizures demonstrated an increase in SMR, suggesting that factors other than seizure occurrence affect mortality. While an excess number of deaths relating to pulmonary events, accidents, extracranial neoplasms, and noncerebral or noncardiac vascular disease were observed, given the person-years of experience in this study, these generally were of borderline significance and there seemed no cause of death unique to those in the study group. RESUME Le taux ďincidence standardisee de mortalite (ISM) a ete determine pour un groupe de patients diagnostiques comme epileptiques residents a Rochester, Minnesota, entre 1935 et 1974. ĽISM pour le groupe total et pour les 29 annees de Ľetude a ete de 2.3. II etait plus bas pour les patients avec epilepsie idiopathique, bien qu'encore significativement plus eleve que Ľincidence attendue. Toutefois plusieurs groupes avec epilepsie idiopathique n'avaient pas un taux de mortalite significativement accru. II s'agit des groupes relatifs a des sujets ayant des absences, des crises partielles et complexes, des epilepsies dont le diagnostic initial avait ete porte entre un et 19 ans, ou des patients de sexe feminin. Chez les patients avec convulsions febriles il n'existait pas de modifications de la mortalite prevue. Chez ceux avec des crises idiopathiques generalisees uniques il y avait une augmentation de la mortalite. Pour le groupe entier, aussi bien que pour tous les cas idiopathiques, Ľaccroissement le plus significatif de ĽISM s'observait dans les 10 premieres annees suivant le diagnostic. II etait aussi significativement accru dans Ľintervalle entre 25 et 29 ans suivant le diagnostic. Ceci suggere, soit un effet tardif associea la predisposition epileptique, soit un effet tardif associea la predisposition epileptique, soit un effet liea la medication chronique, soit une combinaison de ces deux effets. Chez les patients ayant presente une remission des crises il existait un accroissement de ĽISM qui permet de penser que ďautres facteurs que les crises peuvent affecter la mortalite. Bien que Ľon ait observe un nombre excessif de morts liees a des affections pulmonaires, a des accidents, a des neoplasmes extra-craniens et a des affections vasculaires autres que cerebrates ou cardiaques, de telles causes de mortalite restent de signification indeterminee. RESUMEN Se determinaron las relaciones estandardizadas de mortalidad (SMR) para un grupo de pacientes diagnosticados de epilepsia mientras eran habitantes de Rochester, Minnesota entre 1935 y 1974. La SMR fue de 2.3 para la totalidad del grupo habiendo sido seguido durante 29 anos. La SMR fue mas baja para los pacientes con epilepsia idiopatica pero era superior a lo previsto. Diferentes grupos con epilepsia idiopatica no tenian tasas de mortalidad significativamente elevadas. Estos incluyeron pacientes con ausencias, ataques parciales y complejos, epilepsia diagnosticada por primera vez entre 1 y 19 anos de edad y pacientes del sexo femenino. Pacientes con crisis febriles no mostraron alteraciones en la mortalidad prevista. Sin embargo, pacientes con una sola crisis generalizada e idiopatica si evidenciaron un aumento en la mortalidad. Tomando el grupo como un todo, asi como todos los casos con crisis idiopaticas, el aumento mas significativo de la SMR tuvo lugar en los primeros 10 anos despues del diagnostico. La SMR estaba tambien significativamente aumentada en el intervalo entre 25 y 29 anos despues del diagnostico sugiriendo un efecto tardio asociado con la predisposicion para presentar ataques, un efecto relacionado con la medicacion utilizada cronicamente en la terapia o ambos efectos. Pacientes que tuvieron una remision de sus ataques mostraron un aumento en la SMR, sugiriendo que la mortalidad se ve afectada por otros factores aparte la ocurrencia de crisis comiciales. Mientras que un numero excesivo de muertes esta relacionado con enfermedades pulmonares, accidentes, neoplasias extracraneales y enfermedad vascular extracerebral y extracardiaca, considerando el numero de personas y anos de experiencia de este estudio, esas causas fueron de signification dudosa y no parecio existir una causa de muerte unica para aquellos pacientes incluidos en el grupo estudiado. ZUSAMMENFASSUNG Standardisierte Mortalitatsziffern (SMR) wurden fur eine Gruppe von Patienten bestimmt, bei denen erstmalig die Diagnose Epilepsie gestellt wurde und die in Rochester, Minnesota, zwischen 1935 und 1974 lebten. Die SMR fur die gesamte Gruppe wahrend einer 29 jahrigen Beobachtungszeit betrug 2.3. Die SMR war niedriger fur Patienten mit idiopathischer Epilepsie, obwohl sie noch significant hoher als erwartet blieb. Mehrere Gruppen mit idiopathischer Epilepsie hatten keine signifikant erhohten Mortalitatsraten. Das betraf Patienten mit Absencen, partiellen und komplexen Anfallen, Epilepsien, die erstmalig zwischen einem und neunzehn Jahren diagnostiziert wurden und weibliche Patienten. Patienten mit Fieberkrampfen zeigten keine von den Erwartungswerten abweichende Mortalitatsrate. Patienten mit einzelnen idiopathischen generalisierten Anfallen hingegen zeigten eine erhohte Mortalitat. Fur die gesamte Gruppe ebenso wie fur alle idiopathischen Falle bestand die groste Erhohung der SMR innerhalb der ersten 10 Jahre nach der Diagnosestellung. Die Intervall-SMR war auch signifikant zwischen dem 25 und 29. Jahr nach der Diagnosestellung erhoht. Das last entweder an eine Spatwirkung, verbunden mit einer Pradisposition fur Anfalle denken, an eine Wirkung der chronischen Medikation als Therapie der Epilepsie oder an eine Kombination beider. Patienten in Anfallsremission zeigten eine Erhohung der SMR, was darauf hindeutet, das andere Faktoren als das Auftreten von Krampfen die Mortalitat beeinflusst. Obgleich eine uberzufallige Haufigkeit von Todesfallen bei pulmonalen Infekten, Unfallen, extrakraniellen Neoplasien und nicht-cerebralen sowie nicht-kardiovaskularen Erkrankungen beobachtet wird, ist diese Bedeutung–bezogen auf die summierten Beobach-tungsjahre aller Personen dieser Untersuchung–nur von grenzwertiger Bedeutung; keine Todesursache scheint einzigartig zu sein fur die untersuchte Gruppe.

An epidemiologic study of coronary heart disease in residents of Rochester, Minnesota, has been updated through 1982. Between the time that mortality rates began to decline in the late 1960s and now, the age-adjusted incidence of all types of coronary heart disease in residents of Rochester decreased 11% in men but increased 9% in women. This difference was due mainly to changes in the incidence of myocardial infarction as the initial manifestation of coronary heart disease-in men, the rates declined by 20%, whereas the rates for women increased by 17%. The greatest changes were in the age group 50 to 69 years. From the 1965 through 1969 period to the 1979 through 1982 period, the age-adjusted incidence of sudden unexpected death as the initial manifestation of coronary heart disease decreased in both sexes, but the incidence of angina pectoris increased in both men and women. The 24-hour and 30-day case fatality rates for myocardial infarction and the incidence rates for sudden unexpected death have stabilized. Additional studies are needed to identify the reasons for the striking divergence in secular trends in coronary heart disease for men as compared with those for women.

From 1958 through 1980, 131 patients had repair of ruptured chordae tendineae of the mitral valve; 62% were men. Ages ranged from 5 to 70 years (median 57). Chordae to the anterior mitral leaflet were ruptured in 44 patients (34%), to the posterior mitral leaflet in 85 (65%), and to both leaflets in two patients (1%). The mitral valve was repaired by leaflet plication without resection in 116 patients, plication after wedge resection of the unsupported leaflet in six, Ivalon sponge buttress of the posterior leaflet in three, resuspension of chordae in two, and annuloplasty alone in the remaining four. Mitral valve annuloplasty was performed in addition to leaflet repair in 115 patients (88%). Operative (

Publisher Summary This chapter describes the dopamines- β -hydroxylase (DBH) activity in serum. The DBH activity found in blood is biochemically similar to DBH activity in the adrenal medulla and sympathetic nerves with regard to co-factor requirements, requirement for oxygen; Michaelis–Menten constant for substrate, and response to the addition of cupric ion to inhibit endogenous inhibitors of the enzyme. Starch block electrophoresis of serum DBH activity, and the enzyme activity found in sympathetic nerves, and the adrenal medulla has demonstrated that there are differences in the electrophoretic mobilities of the DBH activity among various species, but that within a given species the enzymatic activity found in the blood has the same electrophoretic mobility as that found in other tissues. Immunochemical studies have shown that there is immunochemical cross reactivity within a given species of serum DBH with antibody formed in response to the purified adrenal enzyme from that same species.

A deterministic model is developed to describe a single wave of influenza A in a closed stratified population. The model specifies agent characteristics and nonhomogeneous mixing patterns among various age groups in a standardized American community. Attack rates predicted by the model for the Asian and Hong Kong strains of influenza are found to agree with those predicted by a previously described stochastic simulation model. The deterministic model is then coupled with an optimization formulation which selects the optimal vaccine distribution pattern among the various age groups when there is a limited quantity of vaccine available. Optimal vaccine distribution patterns are given. These patterns are found to vary, depending on the particular strain of influenza A modeled, the quantity of vaccine available, and the “cost” structure of the objective function.

The incidence, trend over a 41-year period, prevalence, familial aggregation, and survivorship of Crohn's disease in the population of Olmsted County, Minnesota, are described. During the period 1935-1975, there were 103 incidence cases; the age-adjusted incidence rate per 100,000 rose from 1.9 (1935-1954) to 4.0 (1955-1964) and to 6.6 in the most recent period (1965-1975). The increase of the rate over the last 11 years is due largely to the increase among persons 20 to 29 years old. No difference in the rates by sex was found. The urban rates were higher than the rural for both sexes and in each interval of the study. The prevalence of Crohn's disease among the residents of Olmsted County on Jan. 1, 1976, was found to be 105.7 per 100,000 population. The relatively high prevalence rate reflects the chronic nature of the disease, the recent increase of incidence, the completeness of case ascertainment, and the high survival rate among these patients.

The long-term effects of milk diets in infancy on the blood serum cholesterol concentrations were studied in 97 school children 7–12 yr of age. Detailed histories were available for these children with respect to their diets during infancy. The major criterion for inclusion in the study was milk (human milk, cow's milk, or commercial formula) as the exclusive source of diet cholesterol during the first 3 mo of life. Fasting blood cholesterol and triglycerides were measured in these 97 school children, and the current diets of 29 of the 97 were evaluated for daily cholesterol intake. A 7-day diet diary was recorded, the food intake was measured and analyzed for nutrients, and validity of the diets was verified by determination of urinary nitrogen excretion. Results of the study showed that the school children fed a low cholesterol formula during infancy had a mean serum cholesterol value 7–12 yr later that was lower than the mean values of the groups fed greater amounts of cholesterol in infancy. Analysis of current diets of 29 of the 97 school children showed that their current dietary intake of cholesterol did low. Dietary intake of cholesterol did not have a noticeable effect on the serum cholesterol levels of the 29 children.

This study is based on 435 consecutive patients age 50 or less who had coronary arteriography. There were 335 patients with coronary artery disease and 100 with normal coronary arteries. Risk factors reviewed were "packet-years" of cigarette smoking, family history of coronary disease in first-degree relatives 50 years of age or less, age- and sex-corrected serum cholesterol and triglycerides, hypertension, and diabetes. By univariate analysis, each risk factor except hypertension and diabetes was significantly more frequent in patients with coronary disease than in those without. By multivariate analysis of all risk factors in patients with and without coronary disease, the male or female patient with coronary disease could best be identified by the strong family history, cigarette smoking history, and age- and sex-corrected serum cholesterol. The percentage of patients with coronary disease when the three risk factors were present was 95%, two factors present 88%, one factor present 67%, none of the three 25%, strong family history alone 90%, smoking alone 66%, and serum cholesterol greater than 80th centile alone 52%.

Two stochastic simulation models for the study of immunization strategies are presented. The first is for influenza in a community of one thousand persons in four age groups and allows for clustering in families, neighborhoods, schools and play groups. The lengths of the latent and infectivity periods are random variables. Variations in susceptibility, illness and withdrawal to the home are considered. Results are given for a number of immunization schedules.The second model is for poliomyelitis in a community in which environmental contamination with competing and interfering enteric agents results in a $50\% $ vaccination failure rate. This is a competitive risk model in which the live virus Sabin vaccine and the wild agent compete with each other and with the contaminating agents. It is shown that immunization can have a major impact on epidemic size even under such adverse conditions.

Histologic, ultrastructural, chemical, and statistical methods were used to study liver biopsy and autopsy specimens from 43 patients who had primary sclerosing cholangitis (PSC), with or without chronic ulcerative colitis (CUC), and from 19 patients who had CUC without PSC. In all study groups, essentially the same abnormalities were found in the hepatic parenchyma outside the major bile ducts, although nondiagnostic tissue samples were observed also. Specimens from patients with extrahepatic PSC were indistinguishable from those from patients with combined extra- and intrahepatic PSC. Common findings included periductal fibrosis and inflammation, portal edema and fibrosis, focal proliferation of bile ducts and ductules, focal bile duct obliteration and loss of bile ducts, copper deposition, and cholestasis. Proliferation of bile ducts in some portal tracts and obliteration or absence of bile duct in others were the most characteristic changes. In most specimens, inflammatory changes appeared mild, yet biliary cirrhosis had developed in 34% of the patients. Specimens from patients with PSC, with or without CUC, more often contained bile and strikingly increased stainable copper (Grades 2 and 3) than did specimens from patients with CUC without PSC. Hepatic copper contents, measured by atomic absorption spectrophotometry, also were higher in specimens from patients with PSC. Study of PCS specimens by transmission electron microscopy and by energy-dispersive X-ray microanalysis revealed that most copper was sequestered in lipolysosomes. The recognition of strikingly similar morphologic features in many liver specimens from patients with either PSC or CUC or both suggests that the causes of these conditions are closely related.

Employment and recreational patterns were analyzed in 279 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) for treatment of symptomatic coronary artery disease. PTCA was successful in 180 patients (65%). When it was unsuccessful, coronary artery bypass graft surgery was usually performed (80%). Return-to-work rates were high irrespective of the outcome of PTCA. Of patients employed full-time or part-time before treatment, 98.5% of those who had successful PTCA alone and 97% of those whose PTCA was unsuccessful but who underwent uncomplicated coronary artery bypass surgery maintained or improved their work status. In a subgroup of men who had been employed in occupations requiring physical labor, 85% of the men whose PTCA was successful returned to work, compared with 68% of those whose PTCA was unsuccessful. The interval from attempted PTCA to return to work was significantly shorter in the successfully treated group; in patients with successful PTCA, the median time to return to work was 14 days, compared with 60 days in patients in whom PTCA was unsuccessful (p less than 0.001). During follow-up, patients with successful PTCA had less angina and were more active in recreational activities than patients who required alternative treatments.

The results of the first thirty months of a long-term prospective study of primary hyperparathyroidism are presented. This study was designed to evaluate the course of asymptomatic patients without complications for whom surgical treatment is deferred as well as the effects of successful surgical treatment on the complications of the disease. Included in the last fifteen months of the study was the measurement of serum immunoreactive parathyroid hormone (IPTH). The majority of the patients without symptoms or complications did well without surgical treatment. Operation eventually was required in 13.8 per cent of these patients. There was no trend in serial serum IPTH values in the thirty patients for whom they were available. Removal of the parathyroid lesion does not ensure cure of primary hyperparathyroidism. Four patients had persistent hyperparathyroidism and three had recurrent hyperparathyroidism among the 171 patients with proved hyperparathyroidism. In patients with significant renal impairment prior to parathyroid surgery further renal deterioration may develop after the removal of an adenoma, but so far this has been reversible. The serum calcium was less than 11 mg/100 ml in fifty-one (31 per cent) of the patients with proved hyperparathyroidism. Serum IPTH values correlated positively with serum calcium values and tumor weights, differing from normal in which there is a negative correlation with serum calcium. Serum IPTH values have been most useful in the evaluation of hypercalcemia when the etiology is not clear. Renal lithiasis was present in 51 per cent of the patients with proved hyperparathyroidism but was thought to be metabolically active in only 10.5 per cent. Roentgenographic bone disease, occurring in 24 per cent of patients with proved hyperparathyroidism, appeared to represent a subpopulation with higher serum calcium, alkaline phosphatase and IPTH values as well as larger tumors. Primary hyperparathyroidism may be much more common than previously suspected, occurring frequently in an asymptomatic form without complications and detected by screening technics. As yet, it is not clear which of these patients should have surgical treatment.

All residents of Rochester, Minn., with a diagnosis of cancer of the colon or rectum during the 30-year period, 1940 through 1969, were identified from the records of the Mayo Clinic and the other resources in the Rochester epidemiologic central file. The medical records and microscopic slides on these patients were reviewed, and 439 met the necessary residency and diagnostic criteria. Adjusted average annual incidence rates per 100,000 for the entire time period for cancer of the colon were 33.0 for males and 24.6 for females and for rectal cancer, 16.3 for males and 13.7 for females. Age-specific incidence rates increase progressively with age for cancer in both sites. Age-adjusted rates for both colon and rectal cancer were consistently higher for males than for females in the three decades studied. However, for both sites, the male predominance appeared only in those patients more than 60 years of age. In this study, we were unable to demonstrate significant increases in incidence rates in either sex for cancer of the colon or rectum over the 30-year period.

Specific immunization has long been a basic tool in medical practice and in local, state, national and international public health. However, the protection afforded by such immunization has been largely limited to the persons immunized because: 1) the usual sources of infection are extra-human (tetanus, yellow fever); 2) spread is primarily by indirect means (typhoid); or 3) those immunized may remain at least partially susceptible to infection and, hence, continue as potential links in the future spread of agents transmitted by contact (diphtheria, pertussis, Salk-type inactivated polio vaccine). An important exception has been vaccination against smallpox which does induce solid though temporary resistance to infection. Presumably as the result of systematic vaccination, endemic smallpox has disappeared from large areas

Summary Fifty livers with carcinoma and sarcoma metastases, malignant lymphoma, or malignant hepatoma were studied; 47 livers were from adult patients. Although most livers had widespread tumor involvement (particularly in the anatomic right lobe), morphometric studies revealed that the hepatic parenchyma of all but six (13%) of the adult livers weighed more than 1 kg. Only two of the eight cases with hepatic failure had parenchyma that weighed less than 1 kg. Twenty-eight per cent of the tumor-bearing livers had parenchyma weights that exceeded the estimated 95 th percentile in nontumor controls. The hepatic parenchyma weight in these instances more often seems to be increased rather than decreased. If there is a decrease of hepatic parenchyma, this is rarely sufficient to cause hepatic failure. The median hepatic parenchyma weight in livers with tumor was greater than of a tumor-free control group. No relationship was noted between hepatic parenchyma weight and clinical evidence of hepatic failure, body weight changes, sex, age, and type, distribution or weight of tumor within the liver.

A new, more general, stochastic model of epidemics is described. This model, one in a continuing series by Elveback and co-workers, includes provision for more complex, pseudo-sociologically stratified populations. Other major new features include the use of several types of conditional probabilities and of time-varying patterns of infectiousness to enable a more detailed simulation of individual and time-related differences in reactions to the infectious agent. A specific computer implementation of one and two-agent versions of this model is illustrated. Plans for additional computer-based simulation studies are discussed, for this and related models.

Multiple myeloma was diagnosed in six residents of Thief River Falls, Minn. in 1968 (a rate of 84/100,000). A survey of the normal population for monoclonal serum protein peaks was undertaken in 1969. Serum from 1200 residents of the city, who were 50 yr of age or older, was collected. Fifteen (1.25%) had monoclonal serum protein peaks: IgG in 11, IgA in one, and IgM in three, with kappa in 11 and lambda in four. No clinical, laboratory, or roentgenographic evidence of myeloma or macroglobulinemia was found in any of the patients. The incidence of monoclonal serum protein peaks is similar to that reported from Sweden. It was concluded that there was no significant increase in monoclonal proteins in the population of Thief River Falls. The 1968 socalled epidemic of multiple myeloma in Thief River Falls remains unexplained.

Various extensions of a stochastic model illustrating the spread of virus epidemics have been simulated. As assumptions and hypotheses concerning the basic model have been added and tested, the computer programs designed to run the simulation have increased in complexity. With this increase it has been necessary to reduce the amount of time and effort involved in setting up computer runs. Default parametric values, alphanumeric coded control cards, different levels of trace options, and simplified summaries have enabled these model extensions. Studies have been conducted on the effects of varying vaccination schedules, contact rates, the interference phenomenon and population composition. Future models have been defined to investigate more complicated transfer patterns and withdrawal from population mixing of those cases in whom illness may result from infection, as for influenza. These studies have been of value to epidemiologists and have encouraged the continuing design of alternate models of a more specific and complex nature.

Serum α1-acid glycoprotein was studied in 31 controls and 130 patients with chronic ulcerative colitis (no liver disease) judged clinically to be either quiescent (25 cases), mildly (38 cases), moderately (34 cases), and severely (33 cases) active. This serum glycoprotein is increased in ulcerative colitis when the disease process is active. For example, the highest observed value in the 31 controls was 111 mg per 100 ml, the lowest value in the 34 moderately active cases was 149, and the lowest value in the severely active cases was 290. After colectomy and proctectomy for chronic ulcerative colitis, serum values declined to normal range (25 cases). In the presence of hepatic disease (cholestasis and chronic hepatitis, both with and without cirrhosis), serum glycoprotein values tended to reflect the degree of activity of the ulcerative colitis (17 cases). The serum value for α1-acid glycoprotein is a more reliable index to the degree of activity of the inflammatory process in ulcerative colitis than is the sedimentation rate. It might serve as a guide to the efficacy of controllable therapeutic procedures for chronic ulcerative colitis, since it has been shown that surgical removal of actively diseased colon and rectum produces glycoprotein values within the normal range and that the receding of severely active chronic ulcerative colitis to the quiescent phase induces glycoprotein values within or slightly above the normal range.

Histologic study of serial biopsy specimens in a prospective, controlled, double blind, randomized trial of treatment involving 63 patients with predefined clinical and biochemical criteria of severe chronic active liver disease revealed five different histologic patterns of hepatic injury on initial biopsy: chronic persistent hepatitis, chronic aggressive hepatitis, subacute hepatitis with bridging, subacute hepatitis with multilobular necrosis, and cirrhosis. The initial biopsies in the fatal cases revealed cirrhosis, subacute hepatitis with multilobular necrosis, or subacute hepatitis with bridging. Patients with subacute hepatitis with bridging and with multilobular necrosis more frequently revealed stigmata of viral hepatitis and more frequently developed cirrhosis than chronic aggressive hepatitis, regardless of treatment. The severe forms of hepatitis more frequently remitted to the histologic features of chronic persistent hepatitis in patients treated with prednisone and a combination of prednisone and azathio-prine than with azathioprine or placebo alone. Serial biopsy specimens frequently revealed changes in the histologic pattern before remission to chronic persistent hepatitis. Histologic progression to cirrhosis may occur by bouts of intralobular and multilobular necrosis as well as by piecemeal necrosis. Sampling error in needle biopsy of cirrhosis is so great that the condition either may be missed or may be impossible to accurately classify into portal and postnecrotic cirrhosis. Observations at autopsy always revealed postnecrotic cirrhosis characterized by extensive parenchymal loss and incomplete regeneration. We conclude that the evolution of any lesion is influenced by at least two factors: the original histologic pattern and the therapy applied.

Data from 1,156 patients greater than or equal to 30 years of age who underwent aortic valve replacement alone or with coronary artery bypass grafting from 1967 through 1976 (early series) and 227 similar patients operated on during 1982 and 1983 (late series) were reviewed. In the early series, 414 patients (36%) had preoperative coronary arteriography (group 1): group 1A (n = 224) did not have coronary artery disease, group 1B (n = 78) had coronary artery disease but did not undergo bypass grafting and group 1C (n = 112) had coronary artery disease and underwent bypass grafting. The 742 patients in group 2 did not have preoperative arteriography. Operative mortality rates (30 day) in groups 1A, 1B, 1C and 2 were 4.5, 10.3, 6.3 and 6.3%, respectively (p = NS). The 10 year survival in both groups 1 and 2 was 54%; in groups 1A, 1B and 1C it was 63, 36 and 49%, respectively (1A and 1B, p less than 0.01). In the late series, the 227 patients were divided into similar groups (group 1A, n = 73; 1B, n = 32; 1C, n = 99), and 90% had preoperative coronary arteriography. Operative mortality rates (30 day) for groups 1A, 1B and 1C were 1.4, 9.4 and 4.0%, respectively; that for group 2 (no preoperative arteriography, n = 23) was 4.3%. Definition of coronary anatomy by angiography seems important in most patients greater than or equal to 50 years old who are candidates for aortic valve replacement, and bypass grafting is recommended for those with significant coronary artery disease.

In an attempt to resolve the uncertainty concerning normal values for leukocyte counts and their possible variation with age and sex, total and differential leukocyte counts in 507 healthy adults were analyzed. Values approximated those previously reported, with the exception of lymphocytes, for which our 97.5 percentile was lower. No significant variation was noted with age and sex.

Three simulation models for stochastic discrete-time epidemics involving two competing and interfering viruses in highly structured communities were presented.

Dopamine-beta-hydroxylase activity is released into the blood with catecholamines from the adrenal medulla and sympathetic nerves. This enzyme activity has been measured in the blood of 317 normal children and 227 normal adults. A significant sibling-sibling correlation of serum dopamine-beta-hydroxylase values was found in the 94 sibling pairs tested. Frequency distributions of serum enzyme values in both children and adults suggest the existence of two populations with regard to serum activity of this enzyme.

We conducted a case-control study of suspected risk factors for ALS among referral patients seen at the Mayo Clinic. Responses to questions about demographic factors, diet, medical history, travel, infectious disease, and other variables were similar in ALS patients and controls. In all but a few items, the responses of the cases and controls did not differ significantly. A significant level of shared exposure to an exogenous agent or environmental insult among cases was noted mainly for heavy metals.

A statistical data processing program for identifying patients who are likely to have abnormalities on various hematologic laboratory tests is described. The prediction of abnormal levels of serum vitamin B12, serum folate, transferrin saturation, and reticulocyte counts is based on a statistical analysis of the patient’s age, sex, and routine blood cell measurements. The program was developed using data from normal-value studies and data from patients who had these laboratory abnormalities. The sensitivity and specificity of the program were evaluated in a controlled prospective study of about 5,000 ambulatory adult patients. The program’s predictions also were compared with the laboratory tests requested by the patients’ attending physicians. The program was most sensitive for predicting low serum vitamin B12 (74%) and low transferrin saturation (78%). In the prospective evaluation, the predictive values varied from 11% for predicting low serum folate to 65% for predicting low transferrin saturation.