David C. Poskanzer

Adenocarcinoma of the Vagina

Although cancer of the vagina is rare and occurs principally in women over age 50 in the form of epidermoid carcinoma 8 girls (15-22) between 1966 and 1969 with adenocarcinoma of the vagina (clear-cell or endometrial) were seen at 2 Boston hospitals. The 4 controls (female) for each case were born within 5 days of the patient and on the same type of service (ward or private). The association between treatment of the mothers (7 or 8) with estrogen diethylstilbestrol during the pregnancies and the development of adenocarcinoma of the vagina in the girls is highly significant (p less than 0.00001). All 7 mothers began therapy in the first trimester and received either a constant dose administered to term or a continually increasing dose given almost to term. Other factors with lower levels of significance are maternal bleeding in the study pregnancy (p less than 0.05) and any prior pregnancy loss (p less than 0.01). Non-significant factors include maternal age at time of birth smoking in parents intrauterine x-ray exposure and breast feeding.

Prenatal exposure to stilbestrol. A prospective comparison of exposed female offspring with unexposed controls.

Abstract The effects of prenatal exposure to diethylstilbestrol were studied by a prospective cohort investigation of 110 exposed and 82 unexposed females. The general health characteristics of mothers and daughters in both groups were similar. Among the exposed, there were striking benign alterations of the genital tract, which included transverse ridges (22 per cent), abnormal vaginal mucosa (56 per cent), and biopsy-proved adenosis (35 per cent). Among the unexposed there were no ridges and one case of vaginal mucosal abnormality including adenosis (p < 0.0001). Abnormal cervical epithelium occurred in almost all exposed subjects but in only half the unexposed (p < 0.0001). The incidence of vaginal adenosis was highest when diethylstilbestrol was begun in early pregnancy. It was not detected when treatment was initiated in the 18th week or later. Oral contraceptive use and prior pregnancy were associated with less adenosis and erosion, respectively (p <0.05). No cases of cancer were observed. (N Engl J...

Clinical and Angiographic Features of Carotid Transient Ischemic Attacks

To determine the prevalence of radiologically evident carotid stenosis in patients with transient cerebral ischemic attacks, we analyzed 95 consecutive hospitalized patients who during a two-year period had appropriate symptoms and also underwent angiography. Pure transient hemisphere symptoms affected 52 patients, pure monocular blindness occurred in 33, and 10 experienced each type of attack separately. Tight stenosis (less than or equal to 2 mm) or occlusion was present in 49 patients (52 per cent). Thirteen patients showed intracranial-branch occlusion, nine of whom had no notable stenosis. Only two clinical transient ischemic attack features correlated with angiographic findings: in transient hemisphere attacks lasting for one hour or longer, the carotid arteries revealed no notable stenosis (0.05 less than P less than 0.1); and separate hemisphere and ocular attacks in the same patient correlated with tight carotid stenosis. On the basis of the angiographic findings, the study indicates there are several distinct groups of patients with carotid transient ischemic attacks.

Clear-cell adenocarcinoma of the vagina and cervix in girls: Analysis of 170 Registry cases ☆

Abstract One hundred cases of vaginal and 70 cervical adenocarcinomas from the Registry of Clear-Cell Adenocarcinoma of the Genital Tract in Young Females have been analyzed. The age range of the patients was 7 to 29 years, and the frequent association with prenatal exposure to diethylstilbestrol and similar nonsteroidal estrogens was confirmed. The hormone administration began prior to the eighteenth week of pregnancy and was continued for periods ranging from 1 week to almost the entire length of the pregnancy. The total dosages ranged from 300 to 18,200 mg. Although most patients had vaginal bleeding or discharge, 16 per cent were asymptomatic. Abnormal cytology was the first clue to the diagnosis of cancer in 11 patients, but 21 per cent of the smears were negative. The larger and more deeply invasive tumors were often complicated by lymph node metastases, but these were also encountered in 1 case in which the tumor had an area of only 3 sq. cm. and with another tumor that invaded less than 3 mm. These findings suggest that local treatment of the primary tumor alone may be inadequate in some cases. Recurrences developed in 37 of the patients and 24 of them died, although the follow-up in one third of the cases has been less than 2 years. The recurrences frequently involved the lungs and supraclavicular lymph nodes as well as the pelvis. The very common association of vaginal adenosis and the occasional coexistence of transverse vaginal or cervical ridges provide morphologic evidence of a stilbestrol-related disturbance in the development of the lower Mullerian tract. The results of intravenous pyelography suggest that the development of the urinary tract is not affected. The fact that all the asymptomatic patients with carcinoma have been successfully treated thus far underscores the importance of screening exposed asymptomatic patients in search of early cases. The rarity (9 per cent) of these cancers prior to the age of 12 years suggests that the inclusion of a large population of girls in this age group in a screening program would uncover very few cases. However, such individuals should certainly be examined at any time abnormal vaginal bleeding or discharge develops.

Myasthenia gravis: Evaluation of treatment in 1,355 patients

The Myasthenia Gravis Clinics of Massachusetts General Hospital and The Mount Sinai Hospital were established in 1935 and 1951, respectively. Patients have been seen regularly at each clinic to the present time, and standardized methods of diagnosis, treatment, and follow-up have been carried out over the years. Details concerning diagnosis and treatment are available in previous publications from each clinic.l.2 Thymectomy, in selected cases, has been employed at Massachusetts General Hospital since 1941 and at The Mount Sinai Hospital since 1951. Eight cases were lost to follow-up in Boston before 1942, and 21 cases were lost to follow-up in New York before 1952. Therefore, surgical therapy was available to all but 29 of the total number of patients. Patients in each clinic were surveyed to determine eligibility for inclusion in the study. Adequate information concerning the initial diagnostic evaluation and at least one followup visit were the criteria for inclusion. Pertinent data concerning each patient from the onset of disease to the most recent evaluation or death were processed separately by each clinic, and the information was coded in a uniform manner on IBM cards. The information included sex, race, age at onset, type and

Cohort analysis of Parkinson's syndrome: Evidence for a single etiology related to subclinical infection about 1920☆

Cohort analysis was undertaken of all cases of Parkinsons syndrome seen at the Massachusetts General Hospital between 1875 and 1961. There were 1383 recorded cases which were suitable for analysis. Only 24 cases were located in the 43 years prior to 1918, while 1359 cases were found in the ensuing 42 years. For all cases, the mean year of birth was 1894.3 and the range (mean ± 2 × s.d.) was 1866.7 to 1921.9. Between the group with onset in 1920–1924 and the group with onset in 1955–1959, a period of 35 years, the mean age of the population with Parkinsons syndrome has increased 27 years. When the cases were examined by year of diagnosis, a similar trend was found. Patients with Parkinsons syndrome appear therefore to be part of a cohort of the population aging together. The curve of increasing age was found to correspond well with the mean ages of a population which ranged between ages 5 and 59 in 1920. When a series of cases with known encephalitis lethargica between 1918 and 1920 were examined, it was discovered that they had a mean age of 33.1 (mean ± 2 × s.d. was 3.7–62.5 years). The data indicate that a population very similar to that in which von Economos disease occurred during the epidemic of 1918 to 1921 in the United States has aged at a rate which is remarkably close to that of the increase in age for successive new cases of Parkinsons syndrome as demonstrated in this study. Only 11.2 per cent of our cases gave a history of encephalitis, however. These data would indicate that most cases of Parkinsons syndrome have a single etiology possibly related to subclinical infection in 1918 to 1920 resulting in the onset of Parkinsons syndrome up to 40 or more years later. A corollary of the hypothesis is that a period of 40 or more years may elapse between an initial, presumably infections insult and the development of a secondary manifestation such as Parkinsons syndrome. If the hypothesis is correct, then the cohort with Parkinsons syndrome will gradually disappear and the number of cases diminish. An attempt has been made to project and predict the occurrence of Parkinsons syndrome in Massachusetts. It appears that a precipitous drop will occur prior to 1980 in the number of cases.

Multiple sclerosis in the Orkney and Shetland Islands. I: Epidemiology, clinical factors, and methodology.

An epidemiological and clinical study of multiple sclerosis (MS) in the Orkney and Shetland Islands showed that the prevalence rate of the disease is the highest in the world (309 and 184/100 000, respectively). The clinical entity, MS, is similar to that found in other parts of the world, except that optic neuritis not followed by MS is rare. Analysis of death certificates indicated that MS has probably occurred at the same rate in these islands for nearly a century. Although the incidence of MS is high, the incidence rate has remained constant over time. A rapidly increasing prevalence of MS has occurred in Orkney, with a more modest increase in Shetland, over the past 20 years, which is largely due to an increase in survival. Demographic factors, case ascertainment, and emigration have contributed little to the increasing prevalence of MS in these islands.

Declining incidence of multiple sclerosis in the Orkney Islands

The incidence of MS in the Orkney Islands has been updated from 1941 to September 21, 1983. Since 1965, MS incidence rates have fallen significantly when compared with those for 1941 to 1964. Alterations in age-specific prevalence, mean duration of illness, and mean age of the MS population are consistent with the decline in incidence of MS in recent years. Although the reason for the decreasing incidence is uncertain, it is consistent with the hypothesis that MS may be caused by canine distemper virus.

THE ROLE OF THYMECTOMY IN THE TREATMENT OF MYASTHENIA GRAVIS

Vincent P. Perlo, Barry Amason,* David Poskanzer, Benjamin Castleman, Robert S. Schwab, Kermit E. Osserman, Angelo Papatestis, Lawrence Alpert and Alan Kark The Myasthenia Gravis Clinic of the Massachusetts General Hospital; the Neurology and Pathology Departments, Harvard Medical School, Boston, Mass.: the Myasthenia Gravis Clinic and Departments of Medicine, Pathology and Surgery, the Mount Sinai Hospital, New York, N . Y .

Multiple sclerosis in the Orkney and Shetland Islands. II: The search for an exogenous aetiology.

In Orkney and Shetland, a survey of lifetime events was undertaken in multiple sclerosis patients and two control groups to define shared exposure to an exogenous agent or environmental insult. Analyses of demographic factors, diet, social class and occupation, housing and environment, animal exposure, schooling, travel, infectious disease, and medical history disclosed a remarkable similarity in responses between patients and controls for a majority of questions. However, differences were noted for sanitation, place of residence at onset, and animal exposure. The data give additional support for an exogenous aetiology of multiple sclerosis.