Gangliosides and neurological diseases.
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Biomedical subjects
Publications and source records attributed to M Alter.
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Since viral hepatitis may be the most common form of chronic viral disease in the world, strenuous attempts are being made to reduce the incidence. To achieve this, strategies are being developed by various national and international bodies involving both the immunisation and screening of certain groups of the population. These strategies are by no means universal, and the value of screening specific groups is the subject of much debate. This paper will address a number of the issues related specifically to the question of screening for hepatitis B virus and hepatitis C virus (HBV and HCV, respectively) namely (a) what is screening?; (b) why should we consider screening?; (c) who should we consider screening?; (d) what are the benefits and liabilities of screening?; (e) what constitutes an acceptable screening test?; (f) should we be screening for HBV or HCV?
A community-based, prospective study was carried out in the Lehigh Valley to determine how 5 selected risk factors and their control affected the frequency of stroke recurrence and death after an initial stroke. The initial stroke was verified clinically and by computerized tomography. Between 1987 and 1989, 662 patients with an initial stroke were enrolled and followed regularly every 4-6 months for up to 7 visits. The average follow-up period was 2 years. The risk factors selected included hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus and transient ischemic attacks. Interim death and its cause were noted. Surviving patients were interviewed and examined to determine whether a second stroke has occurred. At enrollment, 51.4% of the cohort was male. The average age of men was 69.6, while women were older, averaging 74.3 years. Stroke types were thrombosis, 14%; embolus, 23%; lacune, 9%; nonspecific infarct, 48%, and intracerebral hemorrhage, 6%. There were 138 deaths (21%) and 81 second strokes (12%) during follow-up. The frequency of risk factors at enrollment was as follows; hypertension, 59%; myocardial infarction, 25%, cardiac arrhythmia, 47% (of which 16% had atrial fibrillation); diabetes mellitus, 29%, and transient ischemic attack, 18%. Of course many patients had multiple risk factors. We analyzed whether the presence of a risk factor at enrollment and its quality of control during follow-up affected stroke recurrence frequency and the mortality rates. These results will be reported in future papers.(ABSTRACT TRUNCATED AT 250 WORDS)
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Population-based studies of Guillain-Barré syndrome (GBS) give crude average annual incidence rates varying from 0.4 to 1.7 per 100,000 population. The reported incidence is influenced by the diagnostic criteria adopted as well as the thoroughness of case-finding. Variations in these account for some of the lack of uniformity between different studies. Data from the Mayo Clinic based on National Institute of Neurological Disorders and Stroke diagnostic criteria and thorough ascertainment methods gave a crude incidence of 1.7 per 100,000 per year (x 10(-5]. Incidence was higher in females (2.3 x 10(-5] than males (1.2 x 10(-5] as well as in older compared to younger people (3.2 x 10(-5) over age 60 and 0.8 x 10(-5) under age 18, respectively). The disease reached a nadir after onset at 8 days on average, and the illness lasted an average of 12 weeks. Most patients (75%) recovered completely. Recent epidemiological studies of GBS suggest no clear secular trend. Incidence does fluctuate with time but not clearly with season. In virtually all studies "triggering" factors are implicated, but they appear to be diverse, making it less likely, from an epidemiological perspective, that a single antigen is of etiological importance in GBS.
The incidence of transient ischemic attacks (TIAs) in the Lehigh Valley was analyzed using the Lehigh Valley Stroke Register based on data collected between July 1, 1982, and June 30, 1986. The overall average annual incidence rate was 22.9 per 100,000 population, and 23.2 and 22.5 per 100,000 population in men and women, respectively. Men had a statistically significant higher age-specific rate of TIAs than women. Our incidence appears to be lower than that reported in earlier studies but, because of methodologic differences, only continued observations in our population and in similar populations using a standardized methodology will resolve the question of whether TIA frequency is, in fact, declining.
We compared carotid artery disease in 99 black and 106 white patients using duplex ultrasonography (B-mode imaging and Doppler spectral analysis). Blacks had significantly less stenosis of the extracranial internal carotid artery than whites. Among the risk factors investigated, hypertension alone, ischemic heart disease, diabetes mellitus, and smoking failed to explain the racial difference. Although carotid stenosis of greater than or equal to 40% correlated significantly with age in both races (p = 0.001 in whites and p = 0.005 in blacks), blacks had significantly less carotid stenosis of any degree even when age was taken into account. Multivariate analysis showed that race is a significant and independent risk factor for carotid stenosis (p less than 0.0001). Hypertension interacting with race was also significant. Our results require verification in population-based studies. Carotid duplex ultrasonography offers a noninvasive method for carrying out such studies.
Mortality attributed to multiple sclerosis (MS) was analyzed for 35 countries around the world using World Health Organization reports from 1965 to 1984. Trends were plotted for the United States and Canada, for various regions of Europe, Israel, South America, Asia, Australia and some Pacific countries. In general, MS mortality has declined steadily in North America and most of western Europe as well as in countries with a western culture but has remained stable or increased in eastern and northern Europe. Although several Mediterranean countries reported a recent increased frequency of MS, it was not (yet?) evident in mortality data. Intensive prospective surveillance of MS frequency trends in selected regions of the world will determine the validity of the trends based on mortality.
We used the Lehigh Valley Stroke Register and a logistic regression model for the odds ratio to study the relative contribution of several factors, considered jointly, to the risk of recurrent ischemic stroke. The factors were hypertension (HT), transient ischemic attack (TIA), myocardial infarction (MI), other heart diseases (OHD), diabetes mellitus (DM), age, and sex. Among these factors MI, OHD, and TIA constituted significantly greater risk than HTN, DM, age, or sex for ischemic stroke recurrence.
We investigated black/white differences in stroke rate (standardized morbidity), severity, and subtype, and the relative frequencies of 5 primary risk factors (hypertension, diabetes, myocardial infarction, other heart diseases, and transient ischemic attack [TIA]) using the Lehigh Valley Stroke Register. Blacks had a statistically significant higher, age-adjusted rate of stroke than whites. We found no differences in stroke severity using our measures but blacks had a statistically higher proportion of lacunar stroke, while whites had a higher proportion of embolic stroke. There were no differences in proportions of thrombotic stroke or intracerebral hemorrhage. The relative frequencies of hypertension, myocardial infarction, other heart diseases, and diabetes were higher for blacks, while the relative frequency of TIA was higher for whites. These observations are consistent with other reports that blacks have a higher frequency of stroke and tend to have more small-vessel cerebrovascular pathology than whites.
A 46-year-old female is described with prolonged, progressive dementia and a brain biopsy consistent with Creutzfeldt-Jakob disease (CJD). She had neither myoclonic jerks nor an electroencephalogram with periodic spikes and suppression. Five of her close relatives were also demented. The nosology of CJD was discussed in the light of this case in which histopathology was characteristic of spongiform encephalopathy but the clinical features were atypical. We concluded that it would be premature to expand the traditional diagnostic criteria to include such cases as having CJD but, at the same time, it would be prudent to handle tissue, linens and surgical instruments as if they were contaminated by the resistant agent of CJD.
We consider the problem of testing that a disease with variable age at onset is an autosomal dominant or recessive genetic trait. Specific reference is made to Alzheimer's disease and recent publications proposing an autosomal dominant inheritance pattern. The pedigree structure allowed is restricted to first-degree relatives of the proband for the dominant and to sibs of the proband for the recessive hypotheses, respectively, in addition to the proband. The sampling method assumed is the one most often used in practice: single ascertainment or sampling pedigrees with probability proportional to size (pps), i.e., to the number of affected individuals within a pedigree who are in the sampling frame. The statistical methodology developed takes the sampling procedure into account and is a generalization of the Kaplan-Meier method of estimating survival functions to pps sampling.
Temple University Hospital participated in a multicenter acute stroke trial but enrolled only one patient out of 192 screened over 2 years; other centers had similar difficulty in patient recruitment. We analyzed our screening data to determine which enrollment criteria created difficulties in recruitment and whether the problem was attributable to any single criterion or to combinations of criteria. Six individual criteria were frequent causes for exclusion; however, greater than 80% of the patients were excluded for multiple reasons. Consequently, modifying or eliminating any single criterion did not appreciably increase patient accrual. Only 17 of 210 possible pairs of criteria occurred with statistically significant frequency (p less than 0.05), and these were most likely random associations. Therefore, only by minimizing the number and stringency of enrollment criteria will patient accrual be at a level that allows the study to be completed in a timely manner with a fiscally reasonable number of centers.
Multiple sclerosis (MS) appears to be more common in technically advanced countries than in underdeveloped regions and migration from one area to another at a young age affects the risk of acquiring MS. One way of explaining both the peculiar frequency distribution and the effect of migration while young is to postulate that an infection early in life decreases the chance of central demyelination. However, no specific infection has been implicated consistently. Alternatively, an aberrant host response to infection in childhood might induce central demyelination. Thus, the aberrant host response could be age-dependent. In seeking associations between age of infection and risk of MS, we observed a direct relationship: where childhood diseases were acquired early in life, the frequency of MS in that population was low; where childhood diseases tended to occur nearer adolescence, MS frequency in that population was high. Since immune responsiveness to antigenic challenges matures through early adolescence, we reason that early infection might be protective and delay in acquiring childhood infections might increase the risk of developing MS. Indeed, in experimental models, the chance of inducing chronic relapsing central demyelination is increased by using adolescent rather than newborn or mature animals. In this paper, epidemiologic evidence showing the strong association between age of infection and risk of MS is presented.
The design and course of a placebo-controlled alpha-2 interferon trial in MS patients are described. No beneficial effect of the interferon on the course of MS could be shown.
Age-specific risk of recurrent stroke for various risk factors, calculated independently, was estimated using the first year of data from the Lehigh Valley Stroke Register. The register is based on a population of more than one-half million. Among the risk factors examined, the highest overall risk of recurrent stroke, 41.4, occurred with a history of at least one transient ischemic attack (TIA). After myocardial infarction (MI), the relative risk of a recurrent stroke was 8.0, while with all other heart diseases combined it was 8.4. With diabetes, the relative risk of a recurrent stroke was 5.6; with hypertension, it was 4.5. The relative risk increased with age after TIA and MI, but not for other heart disease, diabetes, and hypertension, except in the 85+-year-old age group.
Multiple sclerosis (MS) appears to be more common in technically advanced countries than in underdeveloped regions, and migration from one area to another at a young age affects the risk of acquiring MS. One way of explaining both the peculiar frequency distribution and the effect of migration while young is to postulate that an infection early in life decreases the chance of central demyelination. However, no specific infection has been implicated consistently. Alternatively, an aberrant host response to infection in childhood might induce central demyelination. Thus, the aberrant host response could be age-dependent. In seeking associations between age of infection and risk of MS, we observed a direct relationship: where childhood diseases were acquired early in life, the frequency of MS in that population was low; where childhood diseases tended to occur nearer adolescence, MS frequency in that population was high. Since immune responsiveness to antigenic challenges matures through early adolescence, we reason that early infection might be protective and that delay in acquiring childhood infections might increase the risk of developing MS. Indeed, in experimental models, the chance of inducing chronic relapsing central demyelination is increased by using adolescent rather than newborn or mature animals. In this paper, epidemiologic evidence showing the strong association between age of infection and risk of MS is presented.
A nationwide epidemiologic study of presenile dementia of the Alzheimer type (PDAT) with onset through age 60 years was carried out in Israel. The Israeli National Neurologic Disease Register and clinical records of all patients discharged from hospitals between 1974 and 1983 with a neurologic or psychiatric diagnosis suggestive of dementia were reviewed. A total of 71 Jewish patients with onset of PDAT between 1974 and 1978 was ascertained. The age at onset in these patients ranged from 43 to 60 years. The median survival was 8.1 years, with slightly longer survival if onset occurred before age 55 years, even after correction for expected mortality according to age and sex. The average annual incidence rate per 100,000 population at risk was 2.4 in the population aged 40 through 60 years. Although the incidence rates were slightly greater for women, the difference between the rates by sex was not statistically significant. The age- and sex-adjusted incidence of PDAT per 100,000 population was significantly higher in those born in Europe or America (2.9) than in those born in Africa or Asia (1.4). No significant difference in survival was found between these two groups. The curve of the incidence rates by age for PDAT in Israel is continuous with that for senile dementia of the Alzheimer type collected by similar methods elsewhere, which suggests that one disease process may account for both conditions.