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PubMed2002

Uroplakin-III to distinguish primary vulvar Paget disease from Paget disease secondary to urothelial carcinoma.

Paget disease of the vulva can be mimicked by several disease entities histopathologically, but most of these entities can be clinically distinguished from vulvar Paget disease. However, vulvar Paget disease is in itself a heterogeneous group of epithelial neoplasms that can be similar both clinically and histopathologically. The subtypes of vulvar Paget disease include primary Paget disease arising from a pluripotent stem cell within the epithelium of the vulva, and secondary Paget disease of the vulva. Secondary vulvar Paget disease results from spread of an internal malignancy, most commonly from an anorectal adenocarcinoma or urothelial carcinoma of the bladder or urethra, to the vulvar epithelium. We have recently proposed that these lesions be classified as primary (of cutaneous origin) or secondary (of extracutaneous origin). These subtypes can present similarly as eczematoid skin lesions and may appear similar on routine hematoxylin and eosin-stained slides. Immunohistochemical studies can help differentiate between them. Our current study includes 17 patients with a pathologic diagnosis of vulvar Paget disease. We performed a panel of immunohistochemical stains, including cytokeratin (CK) 7 and 20, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and uroplakin-III (UP-III). Of these 17 patients, 14 (80%) had primary intraepithelial cutaneous Paget disease, 13 without invasion and 1 with associated invasion. Three patients had urothelial carcinoma with spread to the vulva, manifesting as secondary vulvar Paget disease. Immunohistochemically, primary vulvar Paget disease is immunoreactive for CK 7 and GCDFP-15, but uncommonly for CK 20. Vulvar Paget disease secondary to anorectal carcinoma demonstrates CK 20 immunoreactivity but is usually nonreactive for CK 7 and consistently nonimmunoreactive for GCDFP-15. Vulvar Paget disease secondary to urothelial carcinoma is immunoreactive for CK 7 and CK 20 but nonimmunoreactive for GCDFP-15. In addition, we propose the use of a new, commercially available antibody, UP-III, which is specific for urothelium and, in our experience, is immunoreactive in secondary vulvar Paget disease of urothelial origin. The distinction between these 3 types of Paget and Paget-like lesions is essential in that the specific diagnosis has a significant influence on current treatment. The difference in surgical approach to the subtypes of vulvar Paget disease justifies classifying them into distinct lesions, which may be aided by the use of immunohistochemistry, including UP-III.

Biomarkers, Tumor↗

PubMed2003

Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype.

BACKGROUND: Crohn's disease is a heterogeneous entity. Disease behaviour, characterised as stricturing, penetrating, or non-stricturing non-penetrating, is a clinically important phenotype as it is associated with complications and need for surgery. It has recently been showed that the behaviour of Crohn's disease changes over the course of the disease. AIM: To assess the association between rapid development of a penetrating or stricturing pattern of Crohn's disease and demographic and clinical characteristics as well as NOD2/CARD15 genotype. PATIENTS AND METHODS: A total of 163 patients with a firm diagnosis of Crohn's disease and who had non-penetrating non-stricturing disease at diagnosis were studied. Various demographic and clinical characteristics as well as antisaccharomyces cerevisiae antibody status and NOD2/CARD15 genotype were documented in these patients. These characteristics were compared in subgroups of patients according to evolution of disease behaviour five years after diagnosis. RESULTS: Five years after diagnosis there were 110 (67.5%) patients with non- structuring non-penetrating disease, 18 (11%) with stricturing disease, and 35 (21.5%) with penetrating disease. In multivariate analysis, only disease location and number of flares per year were significantly discriminant between the three subgroups (p=0.0009 and 0.0001, respectively). Ileal location of the disease was associated with a stricturing pattern while a high number of flares was associated with a penetrating pattern. Active smoking was also associated with a penetrating pattern compared with a non-stricturing non-penetrating pattern only. CONCLUSIONS: Early development of stricturing or penetrating behaviour in Crohn's disease is influenced by disease location, clinical activity of the disease, and smoking habit, but not by NOD2/CARD15 genotype.

Adult↗

PubMed1994

The first site of recurrence after complete resection in non-small-cell carcinoma of the lung. Comparison between pN0 disease and pN2 disease.

In the present study, we assessed whether the pattern of postoperative recurrence of non-small-cell lung cancer differed between patients with pathologic N0 disease and those with pathologic N2 disease. We reviewed 231 patients with pathologic N0 disease and 63 with pathologic N2 disease, who had undergone a complete resection from 1980 to 1990, and investigated the first recurrence sites. Seventy-two patients with pathologic N0 disease and 52 with pathologic N2 disease were found to have had postoperative recurrence. Both pathologic N0 disease and pathologic N2 disease recur frequently in distant organs, and the ratio of distant metastasis to local recurrence did not differ between the two diseases. The brain, lung, and bone were the common initial metastatic sites in both pathologic N0 disease and pathologic N2 disease. The brain was the most frequent site of distant metastasis in patients with pathologic N0 disease, whereas, on the other hand, pulmonary metastasis was observed more frequently than brain metastasis in those with pathologic N2 disease. Despite histologic types, the presence of different patterns of initial metastatic sites between pathologic N0 and pathologic N2 diseases was observed. Our results suggest that the sites of metastasis after resection depend largely on such anatomic factors as drainage routes. Namely, in contrast to pathologic N0 disease, pathologic N2 disease has an additional drainage route, which is from the N2 nodes to the superior vena cava (pulmonary circulation). Therefore, the frequency of pulmonary metastasis may increase in patients with pathologic N2 disease.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Selegiline for Alzheimer's disease.

BACKGROUND: Alzheimer's disease is the most common cause of dementia in older people accounting for some 60% of cases with late-onset cognitive deterioration. It is now thought that several neurotransmitter dysfunctions are involved from an early stage in the pathogenesis of Alzheimer's disease-associated cognitive decline. The efficacy of selegiline for symptoms of Alzheimer's disease remains controversial and is reflected by its low rate of prescription and the lack of approval by several regulatory authorities in Europe and elsewhere. Reasons for this uncertainty involve the modest overall effects observed in some trials, the lack of benefit observed in several trials, the use of cross-over designs which harbour methodological problems in a disease like dementia and the difficulty in interpreting results from trials when a variety of measurement scales are used to assess outcomes. OBJECTIVES: The objective of this review is to assess whether or not selegiline improves the well-being of patients with Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials, was searched using the terms 'selegiline', 'l-deprenyl', "eldepryl" and "monamine oxidase inhibitor-B". MEDLINE, PsycLIT and EMBASE electronic databases were searched with the above terms in addition to using the group strategy (see group details) to limit the searches to randomised controlled trials. SELECTION CRITERIA: All unconfounded, double-blind, randomised controlled trials in which treatment with selegiline was administered for more than a day and compared to placebo in patients with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (JSB & LF), pooled where appropriate and possible, and the weighted or standardised mean differences (95%CI) estimated. Where possible, intention-to-treat data were used but usually the meta analyses were restricted to completers' data (data on people who completed the study). MAIN RESULTS: There are 15 included trials. All trials examined the cognitive effects of selegiline, and in addition, 12 trials examined the behavioural and mood effects. The results of 8 trials suggested some beneficial effect of selegiline in the treatment of cognitive deficits and in 3 trials in the treatment of behaviour and mood. The meta-analysis revealed benefits on memory function as evidenced by improvement in the memory tests from several cognitive tests. Pooling the data for all cognitive tests suggested significant benefits in those subjects treated with selegiline as compared to controls. There were benefits in mood and behaviour as demonstrated by measurements on the Brief Psychiatric Rating Scale and the Dementia Mood Assessment Scale. The global rating scales showed no effect of selegiline. Unfortunately, the evidence using standardised global cognitive scales was extremely limited, for both the MMSE and ADAS-cog. A variety of adverse effects were recorded, but very few patients left a trial as a direct result of the intervention. REVIEWER'S CONCLUSIONS: Although the evidence for a beneficial effect of selegiline on patients with Alzheimer's disease is promising there is not yet enough evidence to recommend its use routinely in practice. The individual patient data review will yield further evidence on the effects of selegiline compared to control as would additional studies evaluating the use of selegiline for the endpoints of standardised cognitive scales, clinician impression of global change, dependency and caregiver quality of life.

Alzheimer Disease↗

PubMed1988

Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults. A comparative study demonstrating clinical and immunopathologic overlap.

Linear IgA disease of adults, chronic bullous disease of childhood, and the rare childhood cicatricial pemphigoid currently are regarded as separate clinical entities despite their many shared features. All are sulfone-responsive subepidermal bullous diseases associated with linear IgA deposition at the basement membrane zone. In this paper we present a long-term study of 25 cases of adult linear IgA disease, 25 cases of chronic bullous disease of childhood, and four cases of childhood cicatricial pemphigoid, which has revealed further similarities among all three groups. The morphology and distribution of the cutaneous and mucosal lesions were similar; mucosal involvement was present in 80% of patients with adult linear IgA disease, 64% of those with chronic bullous disease of childhood, and 100% of those with childhood cicatricial pemphigoid, and ocular scarring affected patients in all groups. Remission occurred in 64% of those with chronic bullous disease of childhood (the disease was active in 12% after puberty), 48% of those with adult linear IgA disease, and in no cases of childhood cicatricial pemphigoid. HLA B8 and circulating IgA anti-basement membrane zone antibody were more common in chronic bullous disease of childhood than adult linear IgA disease. There were no absolute differences among the three groups, and we suggest that adult linear IgA disease, chronic bullous disease of childhood, and childhood cicatricial pemphigoid are the same disease, with childhood cicatricial pemphigoid being a more severe form of chronic bullous disease of childhood.

Adolescent↗

PubMed2005

Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study.

BACKGROUND: Chronic kidney disease has been shown to be an independent risk factor for cardiovascular disease in high-risk populations. However, this relationship is inconclusive in community-based populations. METHODS: To clarify this issue, we followed 2634 community-dwelling individuals without cardiovascular disease, aged 40 years or older, for 12 years and examined the relationship between chronic kidney disease and the incidence of cardiovascular disease. RESULTS: During the follow-up period, 99 subjects (56 men and 43 women) experienced coronary heart disease, 137 subjects (60 men and 77 women) ischemic stroke, and 60 subjects (26 men and 34 women) hemorrhagic stroke. In men, the age-adjusted incidence of coronary heart disease was significantly higher in subjects with chronic kidney disease than in those without it (6.2 vs. 2.9 per 1000 person-years) (P < 0.05), but such a relationship was not observed with ischemic stroke. In contrast, in women, the age-adjusted incidence of ischemic stroke was significantly higher in subjects with chronic kidney disease than in those without it (3.4 vs. 2.5) (P < 0.05), while that of coronary heart disease was not. Chronic kidney disease was not found to be associated with the incidence of hemorrhagic stroke. In multivariate analysis, even after adjustments for traditional and nontraditional cardiovascular disease risk factors, chronic kidney disease was found to be an independent risk factor for the occurrence of coronary heart disease in men [hazard ratio (HR), 2.26; 95% CI, 1.06-4.79], and for the occurrence of ischemic stroke in women (HR, 1.91; 95% CI, 1.15-3.15). CONCLUSION: Our findings suggest that chronic kidney disease is an independent risk factor for the occurrence of cardiovascular disease in the general Japanese population.

Adult↗

PubMed1995

Neuroproliferation in the mucosa is a feature of coeliac disease and Crohn's disease.

The pathogenesis of villous damage in coeliac disease is unknown. Change to the delicate neuromuscular core may be significant and this study stained various categories of coeliac disease and controls with neuron-specific enolase (NSE) to examine neurofilaments in the mucosa. The amount of NSE staining was evaluated using computer image analysis. The first part of the study compared coeliac disease with Crohn's disease, carcinoma, and biopsy specimens from normal subjects. There was increased NSE staining in both the coeliac disease and Crohn's disease cases but not in carcinomas or normal controls. This difference was statistically significant. The average value for the coeliac disease patients was 50% higher than that of Crohn's disease patients. The second part of the study compared treated coeliac disease with untreated coeliac disease. Treated coeliac disease cases had normal amounts of NSE staining, which were the same as normal controls. These findings suggest that neuroproliferation is a feature of coeliac disease and Crohn's disease. Both share a common feature--namely chronic inflammation--which has been occasionally associated with neuroproliferation. The fact that neuroproliferation resolves with treatment is further evidence for its association with chronic inflammation. The extra neuroproliferation seen in coeliac disease compared with Crohn's disease may contribute to the architectural abnormalities seen in coeliac disease.

Celiac Disease↗

PubMed2003

Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review.

BACKGROUND: Several recent studies provide evidence that the oral cavity may influence the initiation and/or the progression of lung diseases such as pneumonia and chronic obstructive pulmonary disease (COPD). RATIONALE: Studies have shown that poor oral hygiene and periodontal disease may foster colonization of the oropharyngeal region by respiratory pathogens, particularly in hospital or nursing home patients. If aspirated, these pathogens can cause pneumonia, one of the most common respiratory infections, especially in institutionalized subjects. Other cross-sectional epidemiologic studies point to an association between periodontal disease and COPD. This systematic review examines the literature to determine if interventions that improve oral hygiene reduce the rate of pneumonia in high-risk populations. FOCUSED QUESTION: Do periodontal diseases or other indicators of poor oral health influence the initiation/progression of pneumonia or other lung diseases? SEARCH PROTOCOL: MEDLINE, pre-MEDLINE, MEDLINE Daily Update, and the Cochrane Controlled Trials Register were searched to identify published studies that related variables associated with pneumonia and other lung disease to periodontal disease. Searches were performed for articles published in English from 1966 through March 2002. INCLUSION CRITERIA: Randomized controlled clinical trials (RCTs), longitudinal, cohort, and case-control studies were included. Study populations included patients with any form of pneumonia or chronic obstructive pulmonary disease (COPD) and periodontal disease, as measured by assessments of gingival inflammation, probing depth, clinical attachment level, and/or radiographic bone loss, or oral hygiene indices. EXCLUSION CRITERIA: Limited to studies of humans. DATA COLLECTION AND ANALYSIS: The summary statistics used to analyze the RCTs included weighted mean differences in rates of disease between control and intervention groups. For cohort studies that measured differences in rates of disease between groups with and without oral disease, weighted mean differences, relative risks, or odds ratios were compared. A meta-analysis was performed on the 5 intervention studies to determine the relationship between oral hygiene intervention and rate of pneumonia in institutionalized patients. MAIN RESULTS: Of the initial 1,688 studies identified, 36 satisfied all inclusion criteria and were read. Of these, 21 (11 case-control and cohort studies [study population 1,413] and 9 RCTs [study population 1,759]) were included in the analysis. 1. A variety of oral interventions improving oral hygiene through mechanical and/or topical chemical disinfection or antibiotics reduced the incidence of nosocomial pneumonia by an average of 40%. 2. Several studies demonstrated a potential association between periodontal disease and COPD. REVIEWERS' CONCLUSIONS: 1. Oral colonization by respiratory pathogens, fostered by poor oral hygiene and periodontal diseases, appears to be associated with nosocomial pneumonia. 2. Additional large-scale RCTs are warranted to provide the medical community with further evidence to institute effective oral hygiene procedures in high-risk patients to prevent nosocomial pneumonia. 3. The results associating periodontal disease and COPD are preliminary and large-scale longitudinal and epidemiologic and RCTs are needed.

Consensus↗

PubMed1995

Circulating intercellular adhesion molecule-1(ICAM-1) in sera of patients with Graves' disease and Hashimoto disease.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1), a 80-110 kD glycoprotein, has been found to be a ligand for the lymphocyte function associated antigen-1 (LFA-1) molecule and has important roles in inflammatory and immune mediated mechanisms. ICAM-1 is expressed on thyroid follicular cells of patients with Hashimoto disease and cultured thyroid monolayer cells derived from the thyroid surgical specimen. In addition to the expression of ICAM-1 on the surface of cells, soluble variants of several adhesion molecules have been reported. METHODS: We evaluated the circulating ICAM-1 in sera of representative autoimmune thyroid disease, Hashimoto and Graves' disease, and analyzed correlations between circulating ICAM-1 and thyroid-directed autoantibodies. Sera were collected from 58 patients with autoimmune thyroid disease, 28 patients with Graves' disease and 30 patients with Hashimoto disease. Serum concentrations for circulating ICAM-1 were determined with sandwitch enzyme immunoassay. RESULTS: Compared with normal individuals, mean serum concentrations for circulating ICAM-1 were significantly elevated in patients with Hashimoto disease and antithyroperoxidase-positive Graves' disease. Patients with antithyroperoxidase-positive Graves' disease revealed significantly higher serum circulating ICAM-1 concentrations than antithyroperoxidase-negative Graves' disease. Circulating ICAM-1 showed significant positive correlation with serum titers of antithyroglobulin and antithyroperoxidase antibody (r = 0.44, n = 28, p = 0.009, and r = 0.55, n = 28, p = 0.001 respectively). There was a significant positive correlation between circulating ICAM-1 levels and serum antithyroperoxidase level in the group of autoimmune thyroid disease and also circulating ICAM-1 levels were significantly correlated with serum antithyroperoxidase antibody levels in antithyroperoxidase antibody-positive Graves' disease(r = 0.55, n = 28, p = 0.001) and in Hashimoto disease (r = 0.5, n = 30, p = 0.002). The thyrotropin binding inhibiting immunoglobulins(TBII) showed no significant correlation with circulating ICAM-1 levels. CONCLUSIONS: In the present study, high serum levels of ICAM-1 were associated with autoimmune thyroid disease. Graves' disease and Hashimoto disease and positively correlates with levels of antithyroperoxidase antibody.

Autoantibodies↗

PubMed1995

[Interstitial lung disease in patients with connective tissue diseases].

Interstitial lung disease is a significant prognostic factor in connective tissue diseases. To further clarify clinical and immunological features of interstitial lung disease, we studied 894 consecutive patients with connective tissue diseases first evaluated between 1970 and 1993. Interstitial lung disease was found in 101 of 181 (56%) patients with systemic sclerosis, 92 of 183 (50%) with overlap syndrome, 35 of 76 (46%) with polymyositis/dermatomyositis, and 13 of 444 (3%) with systemic lupus erythematosus (p < 0.05, systemic lupus erythematosus vs. other connective tissue diseases). The presence of interstitial lung disease correlated with decreased survival in systemic sclerosis and in polymyositis/dermatomyositis, but not in overlap syndrome or in systemic lupus erythematosus. Interstitial lung disease in patients with connective tissue diseases was classified into two types: acute (n = 8) and chronic (n = 233). Among the 8 patients with acute disease, 4 (all with dermatomyositis) died of respiratory failure and 3 (all with systemic lupus erythematosus) responded to corticosteroids. Among the 233 patients with chronic interstitial lung disease, 20 had polymyositis/dermatomyositis with anti-aminoacyl tRNA synthetase antibodies and 40 had overlap syndrome with anti-U1 RNP antibodies. Respiratory failure in these patients was not frequent and occurred late in the course of the disease. As a cause of death, respiratory failure was associated with autoantibodies to topoisomerase I and aminoacyl tRNA synthetase but not anti-U1 RNP. Autoantibodies to aminoacyl tRNA synthetases were detected before the development of interstitial lung disease in 9 patients with polymyositis/dermatomyositis. We conclude that the clinical features of interstitial lung disease associated with connective tissue diseases vary with the type of connective tissue disease, and that analysis of autoantibodies can be useful in establishing a diagnosis and in forecasting the course and outcome.

Adult↗

PubMed2003

Reduced dietary salt for prevention of cardiovascular disease.

BACKGROUND: Restricting sodium intake in elevated blood pressure over short periods of time reduces blood pressure. Long term effects (on mortality, morbidity or blood pressure) of advice to reduce salt in patients with elevated or normal blood pressure are unclear. OBJECTIVES: To assess in adults the long term effects (mortality, cardiovascular events, blood pressure, quality of life, weight, urinary sodium excretion, other nutrients and use of anti-hypertensive medications) of advice to restrict dietary sodium using all relevant randomised controlled trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, bibliographies of included studies and related systematic reviews were searched for unconfounded randomised trials in healthy adults aiming to reduce sodium intake over at least 6 months. Attempts were made to trace unpublished or missed studies and authors of all included trials were contacted. There were no language restrictions. SELECTION CRITERIA: Inclusion decisions were independently duplicated and based on the following criteria: 1) randomisation was adequate; 2) there was a usual or control diet group; 3) the intervention aimed to reduce sodium intake; 4) the intervention was not multifactorial; 5) the participants were not children, acutely ill, pregnant or institutionalised; 6) follow-up was at least 26 weeks; 7) data on any of the outcomes of interest were available. DATA COLLECTION AND ANALYSIS: Decisions on validity and data extraction were made independently by two reviewers, disagreements were resolved by discussion or if necessary by a third reviewer. Random effects meta-analysis, sub-grouping, sensitivity analysis and meta-regression were performed. MAIN RESULTS: Three trials in normotensives (n=2326), five in untreated hypertensives (n=387) and three in treated hypertensives (n=801) were included, with follow up from six months to seven years. The large, high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported; only 17 deaths equally distributed between intervention and control groups occurred. Systolic and diastolic blood pressures were reduced at 13 to 60 months in those given low sodium advice as compared with controls (systolic by 1.1 mm Hg, 95% CI 1.8 to 0.4, diastolic by 0.6 mm hg, 95% CI 1.5 to -0.3), as was urinary 24 hour sodium excretion (by 35.5 mmol/ 24 hours, 95% CI 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related. People on anti-hypertensive medications were able to stop their medication more often on a reduced sodium diet as compared with controls, while maintaining similar blood pressure control. REVIEWER'S CONCLUSIONS: Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. Evidence from a large and small trial showed that a low sodium diet helps in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Antihypertensive Agents↗

PubMed2004

Organic dusts and disease: a continuous research challenge.

Research on organic dust during recent years has revealed major clinical effects and some causative agents. Many of the symptoms reported are caused by an inflammation in the airways, characterized by a neutrophil response. This condition can cause a non-allergic asthma. There are also reactions characterized by lymphocyte accumulation and by specific IgE antibody formation. Causative agents identified as bacterial endotoxins, molds, and different allergens.

Asthma↗

PubMed1950