The controversy on the early history of Chagas disease

Recently historians of medicine have proposed three distinctive accounts of early history of Chagas disease (American trypasonomiasis). According to the first the disease, described by the Brazilian researcher Carlos Chagas in 1909, was "deconstructed" in the 1920s and disappeared for about twenty years, then was recovered in the 1940s, mainly through the epidemiological studies of Emmanuel Dias and his colleagues in Minas Gerais (Brazil). According to the second Chagas disease could not be "deconstructed" in the 1920s because it did not exist at that time. Chagas observations were inaccurate and unreliable and did not define a new human pathology. The entity called today "Chagas disease" appeared in the 1930, principally as the result of investigations of Cecilio Roma?a in Argentina. Finally, a third view assumes that "Chagas disease" was constructed gradually between 1909 and the 1950s through the collective efforts of numerous Latino-American researchers. This paper juxtaposes different histories of Chagas disease, and argues that their divergences stems from allegiance to distinct, partly incommensurable epistemological "thought styles". The co-existence of divergent styles of historical investigation, this text proposes, should be perceived as potential source of enrichment of our understanding of the past.     

Trends in mortality among California physicians after giving up smoking: 1950-79.

A study was conducted to assess how lung cancer and other mortality trends among California physicians had been influenced by the high proportion who had given up smoking since 1950. Several sample surveys indicated that the proportion of California physicians who currently smoked cigarettes had declined dramatically from about 53% in 1950 to about 10% in 1980. During the same period the proportion of other American men who smoked cigarettes had declined only modestly, from about 53% to 38%. Using the 1950 American Medical Directory a cohort of 10 130 California male physicians was established and followed up for mortality till the end of 1979, during which time 5090 died. The information from follow up and death certification was exceptionally good. The standardised mortality ratio for lung cancer among California male physicians relative to American white men declined from 62 in 1950-9 to 30 in 1970-9. The corresponding decline in standardised mortality ratio was from 100 to 63 for other smoking related cancer, from 106 to 71 for ischaemic heart disease, and from 62 to 35 for bronchitis, emphysema, and asthma. The standardised mortality ratio remained relatively constant for other causes of death not strongly related to smoking. The overall ratio declined in all age groups at a rate of about 1% a year. The total death rate among all physicians converged towards the rate among non-smoking physicians. By the end of the study period physicians had a cancer rate and total death rate similar to or less than those among typical United States non-smokers. This "natural experiment" shows that lung cancer became relatively less common on substantial elimination of the primary causal factor, cigarette smoking. Other smoking related diseases also became relatively less common, though factors other than cigarette smoking may have contributed to this change.     

Prevalence of dementia and major dementia subtypes in Spanish populations: A reanalysis of dementia prevalence surveys, 1990-2008

Background

To diagnose multiple sclerosis (MS), evidence for dissemination in space and time is required. There is no clear definition on how symptoms and signs of a patient indicate clinical dissemination in space. To provide a uniform approach on this subject, a clinical classification system was described recently differentiating patients with mono- and multifocal clinical presentation. Here we assess the predictive value of clinically defined dissemination in space at first presentation for time to clinically definite MS (CDMS).

Methods

Four hundred and sixty-eight patients with a first episode suggestive of MS were classified as clinically mono- or multifocal by two neurologists blinded to magnetic resonance imaging (MRI) results. These patients were part of the BENEFIT study in which 292 patients were randomized to interferon beta-1b (IFNB-1b) and 176 to placebo. By using Kaplan-Meier statistics the risk for CDMS was studied in mono- and multifocal patients of the placebo group, both with and without taking into account MRI measures of potential prognostic relevance.

Results

Time to CDMS was similar in monofocal and multifocal patients. In monofocal patients, the risk for CDMS over 2 years was significantly higher when ≥ 9 T2 lesions or at least one Gd-enhancing lesion were present at the first event or 3 or 6 months after the first event. In patients with multifocal presentation, these MRI measures had no significant added value in predicting time to CDMS.

Conclusion

These data indicate that a carefully performed neurological assessment of symptoms and signs, combined with lesions on MRI, is important for defining the risk of conversion to CDMS.

Trial Registration

The Benefit trial has been registered under NCT00185211 http://www.clinicaltrials.gov     

Parkinson's disease as community health problem: study in Norwegian nursing homes. The Norwegian Study Group of Parkinson's Disease in the Elderly.

OBJECTIVE--To examine the extent of under-diagnosis and overdiagnosis of Parkinson''s disease and to determine quality of treatment in a defined population. DESIGN--Clinical evaluation of an elderly population. SETTING--40 Norwegian nursing homes. SUBJECTS--3322 residents of nursing homes, of whom 500 were selected by nursing staff for evaluation on the basis of a structured information programme on Parkinson''s disease and 269 were examined in detail by neurologists. MAIN OUTCOME MEASURES--Patients'' scores on clinical rating scales, diagnosis of parkinsonism, and effect of changing drug treatment. RESULTS--169 (5.1%) patients were found to have clinical idiopathic Parkinson''s disease, 31 of whom had not had the disease diagnosed previously. In addition, 31 patients without the disease were taking antiparkinsonian drugs unnecessarily. Eighty patients were judged to be receiving "optimal" treatment. In the remaining 58, the treatment was changed, and 36 patients showed a definite functional improvement after a 12 week observation period. CONCLUSIONS--The quality of life of many elderly patients with Parkinson''s disease could be improved by increasing medical and neurological services.     

Changing character of cervical cancer in young women.

To examine the hypothesis that the pattern of cervical cancer is changing data on women presenting with the disease over 34 years were studied retrospectively. During 1953-86, 2628 women with cervical cancer were referred to a large tertiary referral hospital in Sydney; 418 were aged 35 or less. During the period of review the proportion of young women with the disease increased from under 9% in the 1950s and 1960s to about 25% in the 1970s and 1980s; a similar but less pronounced trend was apparent for the whole of New South Wales in the 1970s and 1980s. The prevalence of less common morphological types of cervical cancer increased throughout the period, particularly in the young. Pelvic lymph node metastases were identified in younger patients with stage Ib and IIa tumours more commonly in the later years of the study, suggesting that the disease was becoming more severe. Overall rates of recurrence improved over time, but an apparent increase in early recurrences was observed in young patients with Ib and IIa tumours and without nodal disease. The results suggest that the clinical and pathological behaviour of cervical cancer changed over the period of review.     

Problems and possibilities in the differential diagnosis of Syndrome Spinocerebellar Ataxia

Differential diagnosis in neurologic patients with spinocerebellar syndrome is complex as a result of the great degree of variability in phenotypic and genetic aspects of more than 200 nosological entities. In the past decade, genetic etiology has been discovered in part of the diseases and the term 'spinocerebellar ataxia' has become, from a neurologic point of view, a loose definition applied to a group of autosomal dominant diseases. Topical extensive literature about differential diagnoses of ataxias usually refers to genetics classification or is produced by a group of radiologists, elektrophysiologists and biologists as well as others in the field. A further problem is that the majority of studies do not take into account other acquired illnesses and diseases which may fundamentally alter the symptomology and course of a primary disease, not to mention the possibility of concomitancy in hereditary diseases. The following article was prompted by daily contact with ataxic patients and related issues raised by colleagues; its goal is to clarify problems faced by child neurologists and neurologists in clinical practice.     

Autoantibodies and Sjogren’s Syndrome in Multiple Sclerosis,a Reappraisal

Background

Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS.

Objectives

To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren’s Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren’s Syndrome.

Methods

Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center.

Results

Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren’s Syndrome.

Conclusions

Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease.     

Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS

Background

Multiple Sclerosis is more common in women than men and females have more relapses than men. In a large international cohort we have evaluated the effect of gender on disability accumulation and disease progression to determine if male MS patients have a worse clinical outcome than females.

Methods

Using the MSBase Registry, data from 15,826 MS patients from 25 countries was analysed. Changes in the severity of MS (EDSS) were compared between sexes using a repeated measures analysis in generalised linear mixed models. Kaplan-Meier analysis was used to test for sex difference in the time to reach EDSS milestones 3 and 6 and the secondary progressive MS.

Results

In relapse onset MS patients (n = 14,453), males progressed significantly faster in their EDSS than females (0.133 vs 0.112 per year, P<0.001,). Females had a reduced risk of secondary progressive MS (HR (95% CI) = 0.77 (0.67 to 0.90) P = 0.001). In primary progressive MS (n = 1,373), there was a significant increase in EDSS over time in males and females (P<0.001) but there was no significant sex effect on the annualized rate of EDSS change.

Conclusion

Among registrants of MSBase, male relapse-onset patients accumulate disability faster than female patients. In contrast, the rate of disability accumulation between male and female patients with primary progressive MS is similar.     

Observational Study Assessing Demographic,Economic and Clinical Factors Associated with Access and Utilization of Health Care Services of Patients with Multiple Sclerosis under Treatment with Interferon Beta-1b (EXTAVIA)

Multiple sclerosis (MS) results in an extensive use of the health care system, even within the first years of diagnosis. The effectiveness and accessibility of the health care system may affect patients'' quality of life. The aim of the present study was to evaluate the health care resource use of MS patients under interferon beta-1b (EXTAVIA) treatment in Greece, the demographic or clinical factors that may affect this use and also patient satisfaction with the health care system. Structured interviews were conducted for data collection. In total, 204 patients (74.02% females, mean age (SD) 43.58 (11.42) years) were enrolled in the study. Analysis of the reported data revealed that during the previous year patients made extensive use of health services in particular neurologists (71.08% visited neurologists in public hospitals, 66.67% in private offices and 48.53% in insurance institutes) and physiotherapists. However, the majority of the patients (52.45%) chose as their treating doctor private practice neurologists, which may reflect accessibility barriers or low quality health services in the public health system. Patients seemed to be generally satisfied with the received health care, support and information on MS (84.81% were satisfied from the information provided to them). Patients'' health status (as denoted by disease duration, disability status and hospitalization needs) and insurance institute were found to influence their visits to neurologists. Good adherence (up to 70.1%) to the study medication was reported. Patients'' feedback on currently provided health services could direct these services towards the patients'' expectations.     

Health departments in the U.S. 1920-1988: statements of mission with special reference to the role of C.-E.A. Winslow.

The mission of local health departments in the U.S. is traced from the 1920s to the present through examination of official promulgations of the American Public Health Association and other organizations. As the communicable diseases came under general control, this mission was conceived more broadly. Nevertheless, in effect their public health role was diminished due to the rapid ascendancy of private and not-for-profit medical care, which consistently sought to keep public health out of potential areas of competition. Thinking both within the public health field (as represented by C.-E.A. Winslow) and outside the public health field (as represented by the American Medical Association), had created boundaries limiting public health's role to preventive medical services. This restriction, in turn, largely excluded the public health field from participation in the tremendous expansion of medical care since World War II. The public health role was further limited in 1970 by the removal of much of environmental pollution from its purview. The sum of these and other forces has left the public health field weakened and in considerable confusion about its role at a time when the resurgence of infectious disease (e.g., AIDS and Lyme disease), environmental hazards, and medical care institutions requires a strong public health presence.     

What do family physicians see in practice?

Health care problems dealt with in their practices were recorded by seven family physicians over a period of 1 year (two others recorded for 3 months), each diagnosis being coded according to the Canuck Disease Classification Index. Problems were classified into four types: physical, psychosocial, diseases of choice (or lifestyle) and diseases of social impact. More than 85% of the 23 108 problems recorded were physical in origin and had physical manifestations. More time was spent on routine checkups and treatment of respiratory disease than on any other activity. Venereal disease and alcoholism were infrequent problems. The family physician is in a favourable position to act as health educator and counsellor and must be throughly trained in the physical aspects of disease.     

Where Do Neurologists Look When Viewing Brain CT Images? An Eye-Tracking Study Involving Stroke Cases

The aim of this study was to investigate where neurologists look when they view brain computed tomography (CT) images and to evaluate how they deploy their visual attention by comparing their gaze distribution with saliency maps. Brain CT images showing cerebrovascular accidents were presented to 12 neurologists and 12 control subjects. The subjects' ocular fixation positions were recorded using an eye-tracking device (Eyelink 1000). Heat maps were created based on the eye-fixation patterns of each group and compared between the two groups. The heat maps revealed that the areas on which control subjects frequently fixated often coincided with areas identified as outstanding in saliency maps, while the areas on which neurologists frequently fixated often did not. Dwell time in regions of interest (ROI) was likewise compared between the two groups, revealing that, although dwell time on large lesions was not different between the two groups, dwell time in clinically important areas with low salience was longer in neurologists than in controls. Therefore it appears that neurologists intentionally scan clinically important areas when reading brain CT images showing cerebrovascular accidents. Both neurologists and control subjects used the "bottom-up salience" form of visual attention, although the neurologists more effectively used the "top-down instruction" form.     

Multiple causes of death and the epidemiological transition in American Samoa

Abstract

Multiple‐cause mortality data were used to examine changing patterns of mortality between 1950 and 1979 in American Samoa. This period coincided with a transition from infectious to chronic diseases as the primary causes of death. The available data indicate that as mortality rates from infections declined, the first chronic disease to increase in frequency was cancer. The absence of a lag period suggests that increased cancer mortality may be a consequence of life extension in the presence of modernization. In contrast, mortality rates from cardiovascular diseases tended to increase only after a lag period. As mortality from infections declined, ischemic heart disease replaced infections as the leading cause of death, in either a total‐mentions or an underlying‐cause model of mortality. The transition to degenerative disease mortality in American Samoa was neither as rapid nor as simple as a tabulation by underlying cause of death indicates. Patterns of change were interrelated.     

History of the Department of Pediatrics Yale University School of Medicine.

The history of pediatrics at the Yale University School of Medicine can be divided into eight historical eras. The "Paleohistorical Era" included colonial figures such as Governor John Winthrop and Hezekiah Beardsley who wrote about children''s disease in colonial times. Eli Ives, Professor of the Diseases of Children at Yale Medical School gave the first systematic pediatric course in America in the first half of the nineteenth century. During the second era, from 1830-1920, the New Haven Hospital was opened. An affiliation between Yale University and the New Haven Hospital led to the formal establishment of clinical departments including pediatrics in the early 20th century. Six eras coinciding with successive pediatric chairman have led the department to its present respected position in American pediatrics. The department''s 75th anniversary in 1996 is an occasion to recognize many of the department''s accomplishments and leaders over the years. It is also a time to reaffirm the mission of the department: to the health needs of the children of Connecticut and beyond, to the advancement of scientific knowledge of infants and children and their diseases, and to the training and educational of the pediatric clinicians, educators and investigators of the future.     

Cerebrospinal fluid α-synuclein levels are elevated in multiple sclerosis and neuromyelitis optica patients during replase

The concept that the immune system plays a central role in the pathogenesis of multiple sclerosis (MS) and neuromyelitis optica (NMO) was indisputable. However, neurodegenerative pathological features including loss of axons and neurons were also found in the lesions of these diseases. α-Synuclein is one of the most abundant proteins in pre-synaptic terminals. Recently, many research show α-synuclein level in CSF may reflect the progression of synaptic dysfunction and neuronal apoptosis. Whether the levels of CSF α-synuclein are changed in MS and NMO patients remain unknown. In this study, CSF α-synuclein was measured by an enzyme-linked immunosorbent assay (ELISA) in MS (n = 18) patients, NMO (n = 22) patients, Parkinson's disease patients (n = 9), and the controls (n = 11). We found concentration of α-synuclein in MS and NMO patients were significantly higher than Parkinson's disease subgroup and the controls. Both MS and NMO revealed an increased disease disability with increased CSF α-synuclein. Thus, CSF α-synuclein may be reflect injure axons and neurons in inflammatory demyelinating diseases.     

G. Ledyard Stebbins, Jr. and the evolutionary synthesis (1924-1950)

This is an historical paper examining the scientific background of George Ledyard Stebbins, Jr. (b. 1906), one of the foremost botanists of this century and one of the architects of the evolutionary synthesis, the intellectual event that brought together genetics and selection theory in the interval between 1920 and 1950. It considers his scientific influence and research, beginning with his Harvard education in 1924 and ending in 1950 with the publication of his book Variation and Evolution in Plants. The paper also more broadly assesses the contributions of other botanists to the evolutionary synthesis, including discussion of the work of Edgar Anderson (1897-1967) and others. It also traces the larger historical patterns of American botany, which saw a shift from East Coast botany as exemplified by Harvard botany, to West Coast botany, as exemplified by California botany.     

Longitudinal assessment of antisaccades in patients with multiple sclerosis

We have previously demonstrated that assessment of antisaccades (AS) provides not only measures of motor function in multiple sclerosis (MS), but measures of cognitive control processes in particular, attention and working memory. This study sought to demonstrate the potential for AS measures to sensitively reflect change in functional status in MS. Twenty-four patients with relapsing-remitting MS and 12 age-matched controls were evaluated longitudinally using an AS saccade task. Compared to control subjects, a number of saccade parameters changed significantly over a two year period for MS patients. These included saccade error rates, latencies, and accuracy measures. Further, for MS patients, correlations were retained between OM measures and scores on the PASAT, which is considered the reference task for the cognitive evaluation of MS patients. Notably, EDSS scores for these patients did not change significantly over this period. These results demonstrate that OM measures may reflect disease evolution in MS, in the absence of clinically evident changes as measured using conventional techniques. With replication, these markers could ultimately be developed into a cost-effective, non-invasive, and well tolerated assessment tool to assist in confirming progression early in the disease process, and in measuring and predicting response to therapy.     

Morphometric and Quantitative Immunohistochemical Analysis of Disease-Related Changes in the Upper (Suburothelial) Lamina Propria of the Human Bladder Dome

The upper (suburothelial) lamina propria (ULP) is a distinct region in the human bladder with dense populations of interstitial cells (IC), fine vascular networks and variable development of muscularis mucosae (MM). It is more and more obvious that the ULP plays an important role in bladder physiology and bladder disease, and in the present study we have quantified changes in the cellular key players of the ULP in bladders from patients with carcinoma in situ (CIS), multiple sclerosis (MS) and bladder pain syndrome (BPS). Tissue samples for the different patient groups were obtained from radical cystectomy-specimens. Standardized immunohistochemistry with a panel of specific cell markers was used to characterise the ULP cellular structures, followed by digitalised morphometry and quantitative staining analysis. Alterations in the ULP area were most pronounced in MS bladders, but also present in BPS and CIS bladders. We observed an increased thickness and increased variability in thickness of the ULP IC area in MS and BPS bladders; a significantly increased development of MM in MS bladders; a changed organization of vascular plexuses in the lamina propria in most pathologic bladders and a changed phenotype of ULP IC: a significantly decreased expression of progesterone receptor in MS bladders and a trend towards decreased expression of alpha-smooth muscle actin in BPS bladders. We show here for the first time the presence of disease-specific changes in organisation and/or phenotype of the different key players of the ULP area in human bladder. The present findings further support the hypothesis that the ULP area is involved and altered in different bladder diseases.     

A case of multiple sclerosis improvement following removal of heavy metal intoxication

Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system (CNS) provoking disability and neurological symptoms. The exact causes of SM are unknown, even if it is characterized by focal inflammatory lesions in CNS accompanied by autoimmune reaction against myelin. Indeed, many drugs able to modulate the immune response of patients have been used to treat MS. More recently, toxic metals have been proposed as possible causes of neurodegenerative diseases. The objective of this study is to investigate in vivo the impact of heavy metal intoxication in MS progression. We studied the case of a patient affected by MS, who has been unsuccessfully treated for some years with current therapies. We examined his levels of toxic heavy metals in the urine, following intravenous "challenge" with the chelating agent calcium disodium ethylene diamine tetraacetic acid (EDTA).The patient displayed elevated levels of aluminium, lead and mercury in the urine. Indeed, he was subjected to treatment with EDTA twice a month. Under treatment, the patient revealed in time improved symptoms suggestive of MS remission. The clinical data correlated with the reduction of heavy metal levels in the urine to normal range values. Our case report suggests that levels of toxic metals can be tested in patients affected by neurodegenerative diseases as MS.