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Biomedical subjects

M Schulzer

Publications and source records attributed to M Schulzer.

At least 73 records · Page 4Linked to original sources
PubMed1995

Optic nerve axon count and axon diameter in patients with ocular hypertension and normal visual fields.

BACKGROUND: At postmortem examination, the authors obtained eight eyes of five individuals with elevated intraocular pressure and normal visual fields to study the axon count and mean axon diameter. METHODS: Automated image analysis was used to calculate the total axon count and mean axon diameter per nerve and per nerve segment for each eye. The authors applied the method of identification analysis to compare each study eye with a corresponding normal eye of patients of the same age. RESULTS: There was no statistically significant difference compared with control subjects for total axon count or segmental axon count for any of the eyes. Two eyes showed a statistically significant difference for mean axon diameter for the whole nerve but not for individual segments of the nerve. CONCLUSIONS: Some eyes subjected to varying duration and magnitude of intraocular pressure elevation with normal visual fields may maintain normal axon counts and mean axon diameters.

Aged↗
PubMed1995

Patterns of asymmetry do not change over the course of idiopathic parkinsonism: implications for pathogenesis.

We investigated the asymmetry of focal deficits of bradykinesia in a cross-sectional study of 198 patients with idiopathic parkinsonism. We have analyzed the difference in Unified Parkinson's Disease Rating Scale (UPDRS) scores between the more and less affected sides in these patients, whose duration of symptoms ranged from 1 to 15 years. There was no significant change in the asymmetry or focality over this period; the deficit for each side progressed faster initially and then approached the normal age-related linear rate of decline. Previous studies indicate that there is an inverse linear relation between the UPDRS bradykinesia score and the nigral dopaminergic cell count. We infer that the rate of death of nigral dopaminergic neurons is predetermined from the time of onset of pathogenesis. The simplest explanation is that a causal event kills some cells and damages others so that they undergo premature death. This sequence of changes could be implemented through environmental (toxic or viral) damage to the genome. Several diverse sources of evidence support this concept.

Adult↗
PubMed1994

Age-dependent decline of nigrostriatal dopaminergic function: a positron emission tomographic study of grandparents and their grandchildren.

Despite postmortem evidence for an age-related decline in nigrostriatal dopaminergic function, position emission tomography (PET) studies have produced inconsistent results. This may be due to differences in methods or of subject selection. To investigate further the effect of age on dopaminergic function, we performed PET with 6-L-[18F]fluorodopa (FD) on 12 pairs of grandchildren and their grandparents. The FD uptake rate constant (Ki) was calculated using a graphical method for the whole striatum to avoid confounding of the results by striatal atrophy. The mean Ki was significantly lower in grandparents (p = 0.020). These PET observations represent in vivo confirmation of postmortem evidence that nigrostriatal dopaminergic function declines with aging.

Adult↗
PubMed1994

Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism.

Previous estimates of the rate of progression of the nigral pathology underlying idiopathic parkinsonism (IP) have been derived mainly from pathological studies that have an inherent selection bias. Fluorodopa positron emission tomography (PET) is a reliable tool for assessing nigrostriatal dopaminergic function in vivo. We performed fluorodopa PET on two occasions, 7 years apart, on 16 patients with IP (age at the time of the first scan, 51 +/- 14 yr [mean +/- SD]) and 10 normal controls (age, 54 +/- 16 yr). For the patients with IP, the average duration of symptoms from the time of diagnosis to the first scan was 4.5 years (range, 1-12 yr); their PET index (striatal-occipital)/occipital ratio, dropped by 1.7% per year, from 0.49 +/- 0.08 to 0.43 +/- 0.08 (p < 0.001). The normals' ratio decreased by 0.3% per year from 0.77 +/- 0.05 to 0.75 +/- 0.10 (p = 0.33). The ratios in the IP group progressed significantly faster than the controls (p = 0.036). The rate of decline in IP represents 7.8% per decade, expressed as a fraction of the normals' initial mean value at 54 years of age. These results also permit power analysis for the design of future studies assessing the effect of treatment on the underlying pathology in IP.

Adult↗
PubMed1994

Positron emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions.

Transient exposure to the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome resembling idiopathic parkinsonism (IP). While IP inevitably progresses, the long-term evolution of MPTP-parkinsonism is unknown. Fluorodopa positron emission tomography (FD-PET) is a reliable tool for assessing nigrostriatal dopaminergic function. We performed FD-PET and clinical assessments on two occasions, 7 years apart, on 10 human subjects exposed to MPTP (age at the first scan, 32.7 +/- 6.9 yr [mean +/- SD], and on 10 normal individuals (age, 53 +/- 16 yr). At the time of their first scan, 5 of the subjects exposed to MPTP were clinically normal and 5 had limited signs of parkinsonism; 5 had new clinical deficits 7 years later. In the subjects exposed to MPTP, the PET index [(striatal-occipital)/occipital ratio] dropped by 2.3% per year from 0.70 +/- 0.10 (mean +/- SD) to 0.58 +/- 0.10 (p < 0.001). This was significantly faster than normal aging (p < 0.01) and similar to the progression observed in IP (p = 0.06). The findings suggest that short-term exposure to MPTP leads to a protracted decline in nigrostriatal dopaminergic function more rapid than occurs in normal aging and similar to IP progression. This is the first evidence that transient exposure to a toxin can cause progressive nigral pathology. At present, the mechanism leading to this progression is unknown. Our findings support the hypothesis that some neurodegenerative disorders may result from transient exposure to an environmental agent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Diagnostic tests: a statistical review.

Common measures of the accuracy of diagnostic tests are reviewed. It is shown that the actual performance (predictive value) of these tests depends not only on their sensitivity and specificity, but also on the prevalence of the disease in the population tested (Bayes' theorem). The effect of an inaccurate "gold standard" on the calibration of a new diagnostic test is discussed. Receiver operating characteristic (ROC) curves are introduced as a tool for selecting an optimal cutpoint for a test, and for comparing different tests. Schemes are given for combining tests to improve their accuracy. When multiple continuous measurements are available, methods of discriminant analysis (and logistic regression) are shown to provide measurement combinations with improved accuracy. Examples and key references are provided.

Diagnostic Tests, Routine↗
PubMed1994

Tendon jerks in Parkinson's disease.

Tendon reflexes were examined in 119 patients with idiopathic parkinsonism (IP) and 40 spouse controls to estimate the type and frequency of any alterations in the reflexes. Forty one of 119 patients and 2 of 40 controls had reflex ratings of 3+ at two or more sites (p < 0.001). There was no correlation of reflex score with the severity of disease or with the cardinal signs of IP. In 21 patients with asymmetric tendon jerks the side with the more active reflexes correlated with the side with greater parkinsonian signs. We conclude that an increase in tendon jerks is a feature of IP. The pathophysiology of this change in reflexes should be investigated further to establish if it is a heretofore overlooked manifestation of basal ganglia dysfunction or a link with other neurodegenerative diseases.

Adult↗
PubMed1994

Lymphocytes from the site of disease are functionally different from peripheral blood lymphocytes and may demonstrate etiologically related antigen specificity.

Over a 12-year period, in vitro synovial lymphocyte responses to microbiological antigen stimulation were measured by the [3H]thymidine uptake method in referred patients with all types of non-crystal, non-septic, inflammatory arthritis. From this large study group comparisons of synovial with peripheral blood lymphocyte (PBL) responses were available in 9 patients with enteric reactive arthritis (ERA), 12 patients with sexually acquired reactive arthritis (SARA) and 18 patients with recurrent or persistent oligoarthritis or with polyarticular 'rheumatoid' arthritis. Employing 2-tailed t tests, analysis of variance (ANOVA) or meta-analysis, as appropriate to the obtained data, significant differences were found between synovial and peripheral blood responses. In only 2 of 9 patients with bacteriologically defined ERA, in only 4 of 12 patients with SARA and in only 2 of 18 patients with oligoarthritis or 'rheumatoid' arthritis did the PBLs show statistically significant responses to the antigen that elicited a significant response from synovial lymphocytes. It is concluded that lymphocytes from the site of disease are often functionally different from PBLs and may demonstrate etiologically related antigen specificity; thus they may be a preferred source of lymphocytes for the investigation of immunologically mediated disease, the etiology of which is not understood. This viewpoint is supported by a recent paper on the specificity of hepatic lymphocytes for a protein of hepatitis C in patients with chronic hepatitis C, and also by the use of tumour-infiltrating lymphocytes for anti-melanoma therapy.

Antigens, Bacterial↗
PubMed1994

Reliability of transcranial magnetic stimulation for mapping the human motor cortex.

Motor mapping using transcranial magnetic stimulation has been applied to the study of adaptive and restorative mechanisms of the motor cortex. To date, the reproducibility of mapping techniques has yet to be investigated in detail and/or confirmed. We report a technique used to map the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) motor cortices of 6 normal volunteers, each studied on 2 occasions separated by several weeks (range of 21-132 days). APB and ADM results were analyzed separately, with area and volume characteristics subjected to analysis of variance. Coefficients of variation, which should be low, ranged from 14% to 37% and coefficients of reliability, which should be high, ranged from 63% to 94%, indicating that the described technique for motor mapping is responsible.

Adult↗
PubMed1994

Errors in the diagnosis of visual field progression in normal-tension glaucoma.

BACKGROUND: Despite strictly defined criteria for visual field progression in the ongoing Normal-tension Glaucoma Study, the authors noted a surprisingly large number of patients reaching the endpoint. Traditional methods could not be used to check the diagnostic accuracy of their criteria, because no "gold standard" was established for distinguishing true change from physiologic long-term fluctuation. METHODS: The authors developed a statistical method based on the results of duplicate tests for progression in their subjects. This method allowed the authors to assess the sensitivity, specificity, and predictive values of their diagnostic criterion. It also estimated the true incidence of progression and provided standard errors for the estimates. RESULTS: The authors found that their original strict criteria for progression, based on duplicate testing, produced false calls of progression 57% of the time. By raising the requirement for deterioration and by repeating the entire sequence of duplicate testing once more, the authors have successfully reduced the rate of false calls to 2%. CONCLUSION: Accuracy in recognizing progression is improved by not accepting small changes as evidence of progression and by confirming the findings on repeat testing.

Diagnostic Errors↗
PubMed1994

Clinical observations on the rate of progression of idiopathic parkinsonism.

The time course of evolution of clinical deficits has been a traditional guide to the nature of the aetiopathogenesis of neurological disease. We studied the influence of ageing and duration of disease on the natural history of idiopathic parkinsonism (IP). Two hundred and thirty-eight patients with IP were examined while off medication. Bradykinesia scores were analysed against patients' age and duration of disease by multiple regression. There was no significant interaction between the effects of age and of duration (P = 0.923). We conclude that age and duration of symptoms influence the natural history of IP additively and independently. Furthermore, the rate of neuronal death is more rapid in the earlier stages of evolution of the pathology; subsequently, the velocity of progression slows down to approach the rate of attrition produced by normal ageing. This time course has implications for possible models of pathogenesis.

Aged↗
PubMed1994

A mathematical model of pathogenesis in idiopathic parkinsonism.

We used our observations relating clinical deficits in idiopathic parkinsonism (IP) to age and to disease duration (Lee et al, Brain 1994; 117: 501-7), to develop a mathematical model of the temporal profile of neurodegeneration in IP. We also examined other sets of relevant published observations and applied three additional assumptions which permitted the formulation of this model. Our model indicates that accelerating or decelerating processes should be excluded as the driving forces behind neuronal death in IP. Mechanisms in accord with the model include: (i) an event that kills some neurons and damages others in such a way that their life expectation is reduced; or (ii) an event that starts a process which is continuously killing healthy neurons at a constant rate. The model enables us to extrapolate back to estimate when the causal event occurred. It also explains why IP proceeds more rapidly in older patients. The model has potential relevance to other neurodegenerative disorders, such as Alzheimer's disease and amyotrophic lateral sclerosis.

Adult↗
PubMed1994

A mathematical model for the prediction of the impact of HIV infection on tuberculosis.

A mathematical model is introduced to study the accelerating impact of HIV infection on the incidence rates of tuberculosis (TB) disease. A sexually active population (15-49 years) is followed cross-sectionally over a period of time. Beginning with the year in which HIV infection was probably first present in the population, the model calculates the growing yearly incidence rates of new TB disease in HIV-positive and in HIV-negative individuals. Model equations, derived by an actuarial method, are developed recursively. Input information required for the calculations includes the age distribution of the study population, pre-HIV annual TB infection rates, annual HIV infection and mortality rates, and estimates of annual TB disease breakdown rates in the absence and in the presence of HIV infection. With correct input data, the model provides a useful blueprint for health agencies in designing effective programmes for curbing the future course of these dual epidemics in the population.

AIDS-Related Opportunistic Infections↗
PubMed1994

Synovial lymphocytes indicate "bacterial" agents may cause some cases of rheumatoid arthritis.

OBJECTIVE: To evaluate synovial lymphocyte response data from "rheumatoid" patients, to determine if "bacterial" antigens caused significant stimulation. METHODS: Two-tailed t tests, analysis of variance, and metaanalysis were applied to 3H-thymidine uptake triplicate/quadruplicate counts, resulting from microbiological antigen stimulation of synovial fluid lymphocytes. RESULTS: In 5 patients with rheumatoid arthritis, maximal synovial lymphocyte responses to chlamydial (in 3) and salmonella (in 2) antigens were significantly greater than to other tested antigens. CONCLUSION: The data, associated with other published data from similar studies, suggest that Chlamydia and pathogenic Enterobacteriaceae may be etiologically related to the arthritis of some patients with rheumatoid arthritis.

Adult↗
PubMed1994

Reproducibility of fluorine-18-6-fluorodopa positron emission tomography in normal human subjects.

UNLABELLED: Fluorine-18-6-fluorodopa (FD) positron emission tomography (PET) is established for measuring nigrostriatal dopaminergic function. This is despite the absence of data on the reproducibility of results. METHODS: With an ECAT 953B/31 tomograph, we performed two or three repeated FD PET scans in 10 normal subjects to measure the scan-to-scan variation in the total striatal uptake rate constant (Ki). RESULTS: We found a scan-to-scan standard deviation (s.d.) of 8.7% of the mean. The between-subject s.d. was 26% of the mean, resulting in a reliability coefficient of 90%. Analysis of the variation in the components contributing to Ki showed a reliability varying from 77% to 86% (depending on the different time points analyzed) for emission data measured by the PET camera. The reliability of the blood radioactivity time course, as reflected by the stretch time, varied from 43% to 81%. The overall reliability for the correction of the blood time course for metabolites of FD was 71%. Variation in the blood radioactivity contributed to the variability of Ki by 50% more than the metabolite correction and by 200% more than the emission data. CONCLUSION: The striatal Ki is a reliable measurement; it has a 95% chance of lying within +/- 18% of its value for an individual normal subject.

Adult↗
PubMed1993

Duration of amyotrophic lateral sclerosis is age dependent.

Since 1985, we prospectively followed 246 patients with ALS. The relationship between the age of developing neurological impairment and disease duration was analyzed in 138 patients (86 men and 52 women) who died. Mean disease duration was 4.0 +/- 3.8 years for men and 3.2 +/- 2.5 years for women. There was an inverse, exponential, relationship between onset age and duration (goodness-of-fit P > 0.05). Mean duration at onset age < or = 40 years was 8.2 +/- 5.0 years compared with 2.6 +/- 1.4 years for patients aged 61 to 70 years (P > 0.001). The ratio of young (< or = 40 years) men to women was 3.6:1. When matched for age, disease duration was the same for patients with bulbar and nonbulbar onsets. We conclude that onset age, but not sex, is the most significant predictor determining disease duration in ALS. Longer survival in younger patients probably reflects their greater neuronal reserve.

Adult↗
PubMed1993

Receiver operating characteristic curve analysis in the prediction of carpal tunnel syndrome: a model for reporting electrophysiological data.

Receiver operating characteristic (ROC) curves were used to predict the risk of carpal tunnel syndrome (CTS). Patients were classified clinically as: (1) normal exam and no symptoms (169 hands); (2) having a motor and/or sensory deficit typical of CTS (115 hands); (3) having a history characteristic of CTS (156 hands); and (4) nondiagnostic symptomatology (122 hands). Electrophysiological studies consisted of median and ulnar motor, sensory, and palmar measurements. Group mean values for group 1 differed significantly from groups 2 and 3 (not 4) for all measurements, but values overlapped considerably. Median distal motor latency (DMML) combined with median-ulnar palmar latency differences (MUPLD) had significantly superior discriminant power than other measurements and correlated highly for all groups (r values = 0.71-0.73). These variables were used to construct ROC curves and prediction tables. The approach used allows one to assign a percentage risk of having a CTS and can be used in outcome studies.

Adult↗