E.Gurney Clark

The Oslo study of the natural history of untreated syphilis: An epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material a review and appraisal

Abstract Nowhere in the world is there a more unique opportunity to learn what happens when early syphilis goes untreated than from the files of Boeck of Oslo, Norway. His scientific conviction as to the inadequacies of the specific treatment of the day led him to withhold treatment from approximately 2,000 patients with primary and secondary syphilis during the twenty-year period, 1891–1910. Community protection from infection was aided by the hospitalization of these patients until all traces of the disease had disappeared (from 1 to 12 months, average 3.6 months). In 1929, his successor, E. Bruusgaard, reported on a follow-up study of 473 of these patients and provided information on the outcome of untreated syphilis, which has formed the basis for prognostic statements on syphilis for more than twenty-five years. Now, in the department of Bruusgaards successor, Danbolt, the entire material has been restudied successfully by Gjestland. This restudy represents a striking example of the application of the modern epidemiologic approach. In addition to the scientific contribution of this investigation, an outstanding illustration of international scientific cooperation has been demonstrated. The remarkable degree of success in obtaining significant information on approximately 80 per cent of the study group, 1,404 Norwegian residents of Oslo of 1891–1910, was undoubtedly due to the careful planning which preceded the tracing efforts. This planning included: (a) a consideration of the nature, extent, and significance of the problem of untreated syphilis; (b) an appraisal of existing information on the subject; (c) the setting up of hypotheses to be tested and questions to be answered; and (d) a detailed outline for a practical experiment design. The pretracing experiment design comprised: the selection of the study group; the listing of possible sources of information; a plan for orderly tracing; a provision for the collection and recording of information; plans for “controls”; and an outline for the analysis of data. Of particular importance is that these features of detailed planning preceded actual data collection. This characteristic of the epidemiologic method is well illustrated by this study. The study was undertaken with the ultimate objective of providing information on the “… natural course of syphilis according to as many indices as the material will allow. …” 1 The questions originally asked of the material were: Among patients untreated for secondary syphilis and with no, some, or unknown subsequent treatment: 1. What are the frequencies of secondary relapse, of benign late syphilis, of late symptomatic syphilis, of life-long latency, and of spontaneous cure? 2. What are the effects on longevity, on causes of death and on mortality over that of nonsyphilitics? 3. Does age at time of infection influence outcome? 4. Does sex influence outcome? 5. What are the effects on the outcome of pregnancy at varying intervals following infection? 6. Is morbidity from conditions other than syphilis greater than among nonsyphilitics? Analysis of this material provides useful information in reference to questions 1 to 4. Unfortunately, it was impossible to collect significant data for question 5 and the matter of congenital syphilis was postponed for future investigation on a more limited scale. Data relating to question 6 will be introduced in a subsequent publication 22 if satisfactory inferences can be drawn about morbidity from an extensive mortality study. The data relating to the remaining four questions are summarized in the following paragraphs. One of the significant contributions of this investigation is the information obtained on clinical secondary relapse: 23.6 per cent of these patients experienced this manifestation within five years of discharge from the hospital (males 22.7 per cent, females 24.0 per cent) and of these approximately one-fourth had multiple episodes. Benign late syphilis occurred in 14.4 per cent of males and 16.7 per cent of females. It was observed as early as the first year after discharge and as late as the forty-sixth year, the majority developing by the fifteenth year. There was some evidence of earlier appearance in females than in males and some suggestion that the probability of development is greater among females. Cardiovascular syphilis was observed to have developed in 13.6 per cent of males and 7.6 per cent of females, no cases occurring in those infected before the age of 15. Neurosyphilis did develop in patients who were infected before the age of 15 but not in males infected after the age of 40. In neurosyphilis there was a 2 to 1 ratio of males to females (males 9.4 per cent and females 5.0 per cent). The mortality from syphilis among males was twice that of females, but in neither sex was it an important cause of death. It was second as a cause of death in males and fifth in females, but approximately 90 per cent of deaths were from other causes. There was a definite excess mortality among these syphilitics as compared to the population group from which they came. No evidence was found to support the idea of the prognostic importance of either clinical secondary relapse or benign late syphilis. The best definition of spontaneous cure is too rigid to permit quantitative evaluation. More practical is a consideration of the extent of disability during the lifetime of the persons involved. It was estimated that between 60 and 70 out of every 100 of these patients went through life with a minimum of inconvenience despite no treatment for early syphilis. This gives no encouragement to withhold treatment because the final outcome in any individual cannot be predicted, and, too, syphilis is still a transmissible disease when untreated and can cause serious difficulties among 30 to 40 out of each 100 who remain untreated. This is probably the most comprehensive study of untreated syphilis that has yet been made, and the great mass of data that has been collected will provide the basis for additional contributions to our knowledge of syphilis infection. This brief review cannot do justice to this monumental piece of work comprising a monograph of some 500 pages, with 83 tables and 12 figures, and an annex of 70 pages with 30 tables and 2 figures. Gjestlands contribution will stand as a model of carefully planned and successfully executed field research and will provide the medical literature with the long awaited restudy of the Boeck-Bruusgaard material.

Genetic factors in primary hypertension and coronary artery disease a reappraisal

Abstract There is evidence of familial concentration in primary hypertension, but it is not known to what extent genetic factors are responsible. Data on genetic factors in coronary artery disease are meager, and interpretations are speculative. There is need for studies in which genetic and other factors are studied together. Study of the family characteristics of relatives of patients and controls can provide information on the interaction of genetic and environmental factors and offer suggestions for the interception of causes and the prevention of these diseases.

Studies in hypertension. III. Analysis of individual blood pressure changes.

The results of a questionnaire on conditions of blood pressure measurement, 5ent out prior to the reported study, revealed wide diversity of opinion as to the most satisfactory conditions for blood pressure measurement. This is an analysis of individual blood pressure changes over a period of 312 weeks measured daily at the same hour among 21 subjects observed at 5-minute intervals during a 25-minute period of rest. Fifteen subjects were examined three times on one or more days (9 a.m., 1:30 p.m. and 4:30 p.m.). Although a few of the subjects in the study had occasional readings above 90 mm. diastolic or 140 mm. systolic, none had sustained pressures above these levels. Among the 383 sessions, the initial casual diastolic reading (within 4 mm.) was the lowest in two-thirds of the sessions. There was little change in readings after 15 minutes of rest. In comparing the observations extending over 312 weeks, it was found that the majority of the subjects had reached both their lowest and highest levels within the first five days. Although there was some tendency for midday readings to be lower than the other, this pattern was not consistent.