Autoimmune disease of the thyroid and colon, with a report of a case of chronic ulcerative colitis in association with Hashimoto's disease and penicillin allergy.
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Autoimmune Diseases↗
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Degos' disease: a distinctive pattern of disease, chiefly of lupus erythematosus, and not a specific disease per se.
Degos' disease, known confusingly as malignant strophic papularis, is an uncommon condition of unknown cause characterized by distinctive infarctive lesions in the skin, gastrointestinal tract, and central nervous system; the lesions at the two latter sites often result in death. We deem Degos' disease to be analogous to lupus erythematosus in the sense that each is fundamentally a systemic pathologic process involving several organs, among them the skin, but, moreover, we regard Degos' disease, in most instances, to be an actual manifestation of lupus erythematosus. Histopathologically, the findings in sections of tissue of skin lesions of Degos' disease are indistinguishable from those of one expression of cutaneous lupus erythematosus; immunopathologically, some patients with morphologic findings stereotypical of Degos' disease display signs characteristic of lupus erythematosus. For these reasons, we consider Degos' disease to be a distinctive pattern of disease, rather than a specific disease per se, just as are erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, Sweet's syndrome, and pyoderma gangrenosum, to name but five of scores of them. The singular pattern that is designated Degos' disease usually is an expression of lupus erythematosus, but, episodically, of conditions like dermatomyositis and rheumatoid arthritis.
Adolescent↗
[Clinical studies on abnormal thyroid stimulators in patients with Graves' disease. II. Clinical significance of measuring TSAb and TBII in patients with euthyroid Graves' disease and patients with hyperthyroid Graves' disease during antithyroid drug treatment].
To evaluate the clinical significance of TBII and TSAb activities in euthyroid and hyperthyroid Graves' disease, these two activities were measured in 8 patients with euthyroid Graves' disease and 29 patients with hyperthyroid Graves' disease during treatment with antithyroid drugs. In 8 patients with euthyroid Graves' disease, TBII activity was detectable only in one patient and TSAb activity detected in 3 patients, these detectabilities being much lower than those in hyperthyroid Graves' disease. However, 2 of 4 patients who had either TSAb or TBII came to have both activities, and one of them became overt hyperthyroid. In patients with hyperthyroid Graves' disease, detectabilities of these activities became lower as they became euthyroid with antithyroid drug treatment, but TSAb tended to be higher than TBII when they remained euthyroid for more than 4 months. Although the majority of the patients who had TSAb and/or TBII activities were T3 non-suppressible, patients with no TSAb and TBII activities did not necessarily show remission of the disease. The present results suggest that patients with euthyroid Graves' disease with both TBII and TSAb may be apt to become hyperthyroid, and that TSAb and TBII activities and T3 suppressibility may not be a definite criteria for the remission of Graves' disease.
Adolescent↗
Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.
OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1999, issue 2). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: Of six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Chronic administration of diuretics (thiazide with spironolactone) reduces mortality in intubated patients. Large studies are needed to assess (1) whether chronic diuretic administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients without long-term toxicity and (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.
Chronic Disease↗
Association of glaucoma with neurodegenerative diseases with apoptotic cell death: Alzheimer's disease and Parkinson's disease.
PURPOSE: To report a possible association of glaucoma with Parkinson's disease and Alzheimer's disease. METHODS: Retrospective chart review (observational case series). The ophthalmologic charts of 49 patients with Alzheimer's disease and of 38 patients with Parkinson's disease were reviewed to determine the occurrence rate of glaucoma among these patients. RESULTS: Glaucomatous visual field defects or cup-to-disk ratios of 0.8 or greater were recorded in 12 patients with Alzheimer's disease (24.5%) and in 9 patients with Parkinson's disease (23.7%). CONCLUSION: Patients with Alzheimer's disease and Parkinson's disease may have an increased occurrence rate of glaucoma.
Aged↗
Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). II. Neurological, psychiatric, and demographic influences on baseline measures of disease severity.
The "Predictors Study" is a prospective cohort study of the natural history of Alzheimer disease (AD), the aim of which is to identify milestones in disease progression and to develop a model to predict disease course in individual patients. The empirical background to this study is based on previous reports that the presence of extrapyramidal signs (EPS), myoclonus, and psychosis in AD may signify greater disease severity at any given stage and a more rapid course of the disease over time. The present analyses were conducted to determine whether these independent "predictor" variables were associated with greater disease severity at baseline within a new cohort of 224 mild AD patients recruited from three different medical centers (in New York, Baltimore, and Boston). Measures of disease severity were provided by the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale (BDRS), which measures functional capacity. Independent variables were EPS, delusions, and slowing of the posterior dominant EEG rhythm. The frequency of myoclonus and hallucinations was too low to permit adequate statistical assessment of their effects at this time. EPS and EEG slowing were associated with low mMMSE scores, whereas delusions were primarily associated with impaired functional capacity. These effects were independent of the influence of age and disease duration. These results indicate that the effects of these independent variables can be detected at mild stages of AD and that these effects can be generalized across different geographical regions.
Aged↗
Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: findings of the national conference on cardiovascular disease prevention.
A workshop was held September 27 through 29, 1999, to address issues relating to national trends in mortality and morbidity from cardiovascular diseases; the apparent slowing of declines in mortality from cardiovascular diseases; levels and trends in risk factors for cardiovascular diseases; disparities in cardiovascular diseases by race/ethnicity, socioeconomic status, and geography; trends in cardiovascular disease preventive and treatment services; and strategies for efforts to reduce cardiovascular diseases overall and to reduce disparities among subpopulations. The conference concluded that coronary heart disease mortality is still declining in the United States as a whole, although perhaps at a slower rate than in the 1980s; that stroke mortality rates have declined little, if at all, since 1990; and that there are striking differences in cardiovascular death rates by race/ethnicity, socioeconomic status, and geography. Trends in risk factors are consistent with a slowing of the decline in mortality; there has been little recent progress in risk factors such as smoking, physical inactivity, and hypertension control. There are increasing levels of obesity and type 2 diabetes, with major differences among subpopulations. There is considerable activity in population-wide prevention, primary prevention for higher risk people, and secondary prevention, but wide disparities exist among groups on the basis of socioeconomic status and geography, pointing to major gaps in efforts to use available, proven approaches to control cardiovascular diseases. Recommendations for strategies to attain the year 2010 health objectives were made.
Cardiovascular Diseases↗
Low-dose intermittent urokinase therapy in chronic symptomatic end-stage arterial disease--clinical relevance for patients with coronary artery disease or peripheral arterial occlusive disease.
Symptomatic end-stage arterial disease in coronary artery or peripheral arterial occlusive disease represents an increasing clinical problem as cardiovascular mortality in these patient groups has declined due to improved secondary prevention. While in peripheral arterial occlusive disease amputation with subsequent life-long physical disability is the major problem, patients with end-stage coronary artery disease and refractory angina pectoris repeatedly report to the emergency ward with the clinical symptoms of unstable coronary syndromes, but myocardial infarction is generally ruled out. For these patients long-term intermittent urokinase therapy has been developed as an alternative treatment modality. Potential mechanisms for clinical effectiveness include improvement of rheological blood properties, thrombolysis of non-occluding arterial thrombi and possibly plaque regression. In coronary artery disease urokinase is applied as an intravenous bolus injection of 500,000 IU urokinase three times a week over a period of 12 weeks. This leads to a marked reduction of fibrinogen by about 35% and of clinical symptoms by around 70% accompanied by a reduction of exercise-induced myocardial ischemia. In observational studies in patients with peripheral arterial occlusive disease injections of 500,000 IU of urokinase were usually given daily for a shorter time period of three to four weeks with a clinical success rate, defined as a cessation or marked reduction of rest pain and/or salvage of a limb, of around 50%. Given the state of critical ischemia in both entities of atherosclerotic disease, long-term intermittent urokinase therapy represents a promising antiischemic approach. In particular in patients with peripheral arterial occlusive disease randomized controlled trials with prolonged treatment periods, which are likely to improve clinical results, are warranted.
Arterial Occlusive Diseases↗
The impact for causal associations between common diseases and inflammatory bowel disease: a disease-wide bidirectional Mendelian randomization study.
OBJECTIVES: Observational studies on associations between various diseases and inflammatory bowel disease (IBD) are often limited by confounding and reverse causation. We aimed to assess potential causal relationships between a wide range of diseases and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We performed a comprehensive bidirectional Mendelian randomization (MR) analysis of 104 common diseases and IBD traits using the generalized summary-data-based MR (GSMR) approach. Genome-wide association study (GWAS) summary statistics for diseases were obtained from the MRC Integrative Epidemiology Unit, and IBD data from the International IBD Genetics Consortium. Summary-data-based MR (SMR) integrating GWAS and expression quantitative trait locus data was applied to identify pleiotropic genes associated with IBD. RESULTS: MR analyses identified 38, 34, and 52 exposures significantly associated with IBD, UC, and CD, respectively. Childhood- and adult-onset asthma showed distinct causal effects on UC and CD. Reverse MR indicated associations between IBD traits and 15 diseases, including multiple sclerosis. SMR identified RGS14 and CARD9 as pleiotropic genes linked to IBD, suggesting shared genetic mechanisms with asthma and multiple sclerosis. CONCLUSIONS: These findings provide evidence for causal links and shared immune-related genetic mechanisms underlying IBD, highlighting potential targets for future research.
Humans↗
Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. The Royal Kings and Queens Parkinson's Disease Research Group.
We examine the evidence for free radical involvement and oxidative stress in the pathological process underlying Parkinson's disease, from postmortem brain tissue. The concept of free radical involvement is supported by enhanced basal lipid peroxidation in substantia nigra in patients with Parkinson's disease, demonstrated by increased levels of malondialdehyde and lipid hydroperoxides. The activity of many of the protective mechanisms against oxidative stress does not seem to be significantly altered in the nigra in Parkinson's disease. Thus, activities of catalase and glutathione peroxidase are more or less unchanged, as are concentrations of vitamin C and vitamin E. The activity of mitochondrial superoxide dismutase and the levels of the antioxidant ion zinc are, however, increased, which may reflect oxidative stress in substantia nigra. Levels of reduced glutathione are decreased in nigra in Parkinson's disease; this decrease does not occur in other brain areas or in other neurodegenerative illnesses affecting this brain region (i.e., multiple system atrophy, progressive supranuclear palsy). Altered glutathione metabolism may prevent inactivation of hydrogen peroxide and enhance formation of toxic hydroxyl radicals. In brain material from patients with incidental Lewy body disease (presymptomatic Parkinson's disease), there is no evidence for alterations in iron metabolism and no significant change in mitochondrial complex I function. The levels of reduced glutathione in substantia nigra, however, are reduced to the same extent as in advanced Parkinson's disease. These data suggest that changes in glutathione function are an early component of the pathological process of Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Death↗
Hypokinesia in Parkinson's disease: influence of age, disease severity, and disease duration.
The aim of this cross-sectional study was to compare the role of aging in measures reflecting diurnal activity and immobility in 60 parkinsonian patients with predominant features of hypokinesia and rigidity and 100 healthy subjects aged 50 to 98 years. In the patients, we also studied the relation between disease duration and subjective and objective measures of disease severity. Motor activity was recorded during 5 successive days at home with a wrist-worn activity monitor. For each subject, two mean measures reflecting the diurnal activity level and the relative proportion of activity and immobility were calculated. Diurnal measures of activity revealed in both groups a prominent absolute reduction of activity and an increase of the time spent without movement ("immobility") with advancing age. Parkinsonian patients showed significantly lower values for both motor-activity measures than did the healthy subjects. The rate of the age-related decline of both diurnal activity measures in both groups, however, is comparable. Disease duration showed no relation with subjective and objective measures reflecting disease severity. This study shows that if care is taken to control for disease severity, the rate of the age-related decline of measures reflecting diurnal activity and immobility is similar in both groups. The lack of relation between disease duration and subjective and objective measures of disease severity suggests that the rate of progression of Parkinson's disease can be reliably studied only by means of longitudinal studies.
Activities of Daily Living↗
Indium 111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion.
Indium 111-leukocyte scanning has recently been introduced as a new method for imaging inflammatory bowel disease. The technique has recently been made more specific for acute inflammation by labeling a pure granulocyte fraction rather than the conventional mixed leukocyte preparation. We now report a prospective study comparing 111In-granulocyte scanning with endoscopy, histology, and fecal 111In-granulocyte excretion for the assessment of disease extent and severity in colonic inflammatory bowel disease. In 52 patients with Crohn's disease or ulcerative colitis, disease extent and severity were assessed macroscopically, histologically, or by scanning using a numerical grading system. Excellent correlations were found between both endoscopy and histology and 111In scans [r = 0.90 (endoscopy) and r = 0.90 (histology) for extent; r = 0.86 and r = 0.91 for disease activity]. Severity graded by scanning also showed a close correlation with fecal 111In-granulocyte excretion (r = 0.90). Indium 111-granulocyte scans are a rapid, accurate, noninvasive means of assessing both disease extent and severity of colonic involvement in inflammatory bowel disease.
Biopsy↗
Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group.
The Modification of Diet in Renal Disease Study was a multicenter trial of the effect of protein restriction and strict blood pressure control on the progression rate of chronic renal failure of multiple causes. At the first baseline visit, 1,795 screened patients with renal disease had blood pressure measured, antihypertensive medications recorded, glomerular filtration rate (GFR) determined by 125I-iothalamate clearance, a nutritional assessment, and a 24-hour urine collection to determine sodium and potassium levels. A total of 1,494 patients in this cohort were classified as hypertensive (83%) and the remainder (301 patients) as nonhypertensive. Ninety-one percent of the hypertensive subjects were on treatment, 54% being controlled to a blood pressure of < or = 140/90 mm Hg. To better understand the factors that contribute to the development of hypertension in chronic renal disease, some determinants of the prevalence of hypertension in this cohort were investigated. Compared with normotensive subjects, hypertensive patients were older (51.2 +/- 12.7 years v 46.6 +/- 13.1 years [mean +/- SD]), had a higher body mass index (BMI; 27.5 +/- 4.7 kg/m2 v 25.4 +/- 4.2 kg/m2), and had a lower GFR (37.8 +/- 19.6 mL/min/1.73 m2 v 50.1 +/- 25 mL/min/1.73 m2). All these differences were significant (P < 0.01). The prevalence of hypertension was significantly higher for men than for women (86% v 80%; P = 0.001), and for blacks than for whites (93% v 81%; P < 0.001). The prevalence of hypertension was higher in subjects with glomerular disease than in those with tubulointerstitial disease (85% v 62.6%; P < 0.001). The prevalence of hypertension varied inversely with GFR (from 66% at a GFR of 83 mL/min/1.73 m2 to 95% at a GFR of 12 mL/min/1.73 m2). The prevalence of hypertension varied directly with BMI (from 70% with a BMI at the 10th percentile to 94% with a BMI at the 97th percentile). This relationship was independent of GFR. Multiple logistic regression analysis showed five predictors in decreasing order of significance as determined by chi-square values: GFR, 83.2; BMI, 36.7; black race, 19.9; increasing age, 14.5 (all P < 0.001); and male gender, 5.1 (P = 0.024). Salt intake was not a determinant of blood pressure status. These results confirm previous reports indicating that hypertension in renal disease is determined by the level of renal function. For the first time, three factors known to predict blood pressure levels in populations with normal renal function were also shown to be determinants of blood pressure in renal disease: BMI, black race, and age. In addition, the data suggest that hypertension is inadequately treated in more than half of patients with chronic renal disease in the United States.
Adolescent↗
Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease.
BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. METHODS: We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. RESULTS: Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. CONCLUSIONS: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.
Aged↗
Chronic bullous disease of childhood and linear IgA disease of adults are IgA1-mediated diseases.
Linear IgA disease is characterized by the presence of linear IgA deposits at the basement membrane zone of the skin, and in some cases by circulating basement membrane zone antibodies. The disease occurs in both adults and children, and is designated adult linear IgA disease in the former and chronic bullous disease of childhood in the latter. The subclass distribution of the circulating and bound basement membrane zone antibodies was studied in 32 children and eight adults. The results were compared with five dermatitis herpetiformis patients and five normal controls. The circulating antibodies (39 patients) and the cutaneous deposits (39 patients) were IgA1 in all 40 patients with linear IgA disease. The cutaneous deposits in dermatitis herpetiformis were also all IgA1, and no circulating antibodies were detected. The controls were all negative. This large series of children and adults with linear IgA disease demonstrates that the circulating and cutaneous basement membrane zone deposits are all IgA1, and suggests that linear IgA disease is an IgA1-mediated disease.
Adult↗
Doppler US in patients with crohn disease: vessel density in the diseased bowel reflects disease activity.
PURPOSE: To determine if neovascularization associated with Crohn disease, as detected with Doppler ultrasonography (US), reflects clinical disease activity. MATERIALS AND METHODS: A devised measurement, vessel density, was estimated with color Doppler US. Patients with Crohn disease underwent clinical and laboratory assessment in which the Crohn disease activity index was measured; patients underwent abdominal US the same week. Color Doppler US was performed by using a 7.5-10.0- or 8.0-12.0-MHz transducer, the lowest possible pulse repetition frequency without aliasing, a low wall filter, and high Doppler gain settings. The length and thickness of the affected loops were measured, and the number of color Doppler signals per square centimeter in the bowel loop was counted. Pulsed Doppler US was used to confirm that the signals originated from arteries or veins and not from movement artifacts. RESULTS: Ninety-two patients (aged 7-20 years; mean, 14.85 years; 44 female, 48 male) underwent 119 examinations; 85 were performed in patients with active disease. Affected loops were thicker (10.6 vs 4. 6 mm; P: <.001) and had a higher vessel density with disease (69 of 119 examinations) than during remission (two of 34 examinations; P: <.001). CONCLUSION: Vessel density in affected bowel loops, as estimated with Doppler US, and bowel wall thickness (>5 mm) reflect disease activity in patients with Crohn disease.
Adolescent↗
[Colonic localization of Crohn's disease. New case reports. Rectocolic Crohn's disease. Colonic Crohn's disease and sigmoid diverticulitis. Colonic Crohn's disease].
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Adult↗
The relationship between Alzheimer's disease, Parkinson's disease and motor neuron disease.
We argue against the dominant status assigned to conventional microscopy in the categorization of disorders such as Alzheimer's disease, Parkinson's disease and ALS. As an example we criticize the emphasis that has been placed on correlating the presence of Lewy bodies with the diagnosis of Parkinson's disease. In essence, we submit that Parkinson's disease can exist without Lewy bodies, and Lewy bodies can exist without Parkinson's disease. Nevertheless, we consider that the newer techniques available to histology have led to an important concept that constitutes a shared feature for Alzheimer's disease. Parkinson's disease and ALS; they are all characterized by the deposition of cytoskeletal debris in tissue, so they may perhaps be collectively termed the "Cytoskeletal Disorders".
Aged↗