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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↗

Disease versus disease: how one disease may ameliorate another.

Systemic disease, either genetic or acquired, may prevent or decrease the severity of another disease. These observations have led to important therapeutic advances. The best-known examples are Edward Jenner's use in 1798 of cowpox to prevent smallpox and J.B. Haldane's 1942 observation that erythrocyte disorders such as thalassemia and sickle cell disease modify the severity of malaria. Patients with and carriers of cystic fibrosis may have genetic resistance to tuberculosis and/or secretory diarrhea. The beneficial effects of undernutrition have led to therapeutic diets for seizures, celiac disease, type 2 diabetes, and inflammatory bowel disease. Finasteride for prostatic hypertrophy was developed after the observation that patients with male pseudohermaphrodism resulting from 5-alpha-reductase mutations do not develop prostatic hypertrophy. Rh immunoglobulin for Rh hemolytic disease prevention followed the observation that ABO incompatibility prevented Rh sensitization. The natural immunosuppression of measles may cause remission of nephrosis, and that of leprosy prevents psoriasis. Patients with one form of agammaglobulinemia (X-linked) never get Epstein-Barr virus infection, and patients with another form (common variable) are seemingly cured by HIV infection. HIV/AIDS is prevented or modified by co-receptor mutations (notably the CCRDelta32 chemokine mutation), HIV-2, or GB virus C infection. Additional exploration of these genetic, infectious, and metabolic influences on disease severity may provide new therapeutic approaches to HIV and other diseases.

Disease↗

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↗

Prevalence of coronary artery disease, lower extremity peripheral arterial disease, and cerebrovascular disease in 110 men with an abdominal aortic aneurysm.

Of 110 men (mean age 66 years) with an abdominal aortic aneurysm, 78 (71%) had coronary artery disease (CAD), 50 (46%) had lower extremity peripheral arterial disease (PAD), and 30 (27%) had cerebrovascular disease. Twenty-four percent of the patients with an abdominal aortic aneurysm had CAD plus lower extremity PAD plus cerebrovascular disease, 22% had CAD plus lower extremity PAD and no cerebrovascular disease, 22% had only CAD, 4% had CAD plus cerebrovascular disease and no lower extremity PAD, and 29% had no CAD, lower extremity PAD, or cerebrovascular disease.

Adult↗

Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease.

PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from other forms of Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large-scale clinical studies were lacking. This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older. Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients. Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered.

Adult↗

Quality of care of children with chronic diseases in Alexandria, Egypt: the models of asthma, type I diabetes, epilepsy, and rheumatic heart disease. Egyptian-Italian Collaborative Group on Pediatric Chronic Diseases.

OBJECTIVES: To evaluate the quality of care delivered to children suffering from index chronic diseases using specific indicators of health care delivery and to study the predictors of suboptimal quality of care (SQC) and its outcome on children. DESIGN: Over a 9-month period, guidelines for optimal care were formulated. A specific questionnaire for every studied chronic disease was prepared in collaboration with the clinicians in charge of the diseased children (66% pediatricians and pediatric specialists and 34% adult specialists). The clinicians were asked to write the details of daily practice, ie, how these children were managed on a routine basis as well as in an emergency situation. A cross-sectional study was conducted over a 4-month period and included 953 children suffering from bronchial asthma (BA), childhood epilepsy (CE), type I diabetes mellitus (IDDM), and rheumatic heart disease (RHD). A systematic random sample of children was selected from children visiting the ambulatory settings of all children's hospitals. Every fourth child was selected on 2 randomly chosen days each week, while all diseased children admitted in the hospital settings of the children's hospitals during the study were included. A general form describing the impact of the diseases on the child was prepared. A network of clinicians was created in all children's hospitals; seminars were held during which the content validity of the questionnaire was tested. Items were evaluated for their internal consistency using the Cronbach alpha. According to the degree of adherence to the recent therapeutic guidelines concerning selected indicators of the quality of care specific to every disease, children were categorized as receiving optimal quality of care or SQC. These indicators were: the use of inhaled bronchodilators in acute asthmatic attacks in mild asthma and the use of the prophylactic drugs (inhaled sodium cromoglycate or inhaled beclomethasone) in moderate to severe chronic BA in between acute asthmatic attacks; compliance with antiepileptic drugs in epileptic children; regular performance of self-monitoring of blood glucose and/or urine testing in diabetic children; and compliance with prophylactic antibiotics in children suffering from RHD. The records of the outpatient clinics for ambulatory and hospitalized cases were reviewed to assess the degree of compliance with the prescribed management before the index visit. Sociodemographic characteristics and health care system-related predictors of SQC were analyzed via stepwise logistic regression analysis. The impact of illness on the child was assessed by 7 items which were: dependence on parents in domestic activities, level of activity compared with peers, mood compared with peers, level of socializing, degree of discomfort attributable to illness, level of physical disadvantage, and urinary incontinence. Factor analysis with Varimax rotation was performed on items related to the impact of illness. Parental satisfaction with care was rated as excellent, very good, fair, or poor. Information on school outcome was obtained by asking the caretakers whether the child was able to attend school regularly despite his sickness. Scholastic achievement was also rated as excellent, very good, good, and acceptable. Parents were asked whether the child had ever repeated a grade because of his sickness. SETTING: Ambulatory and hospital settings of all children's hospitals in Alexandria, Egypt. RESULTS: Only 52% of mild asthmatics were given inhaled bronchodilators during acute attacks and 6.84% of moderate to severe asthmatics were taking prophylactic drugs (inhaled sodium cromoglycate and/or inhaled beclomethasone) between acute attacks. Similarly, only 53 of 134 (39.6%) of diabetic children were regularly performing self-monitoring of blood glucose and/or urine testing. In contrast, in epileptic children, 121 of 173 (69.9%) were judged as being compliant by their managing clinicians and more than two

Adolescent↗

[An autopsy case of Alzheimer's disease associated with Parkinson's disease, compared to 2 autopsy cases of diffuse Lewy body disease].

A 68 year old male, diagnosed as Alzheimer's disease clinically, pathologically showed both findings of Alzheimer's disease and Parkinson's disease. The brain weight was 940 g. Macroscopically, severe cortical brain atrophy and depigmentation of the substantia nigra was noted. Microscopic examination showed marked appearance of senile plaque and a large number of neurofibrillary tangle with sever neuronal loss of the cerebral cortex. Additionally, the loss of neuron with many Lewy bodies was found in the substantia nigra. Lewy bodies were also found in the locus ceruleus and the dorsal vagal nucleus, but few in the cerebral cortical neurons. We compared this case neuropathologically with two autopsy cases of diffuse Lewy body disease (DLBD). There was no distinction concerning the lesions of the brain stem between this case and the cases of DLBD. In all three cases, the nucleus of basalis of Meynert showed marked neuronal loss. However, the brain was lighter than those of the cases of DLBD. Senile changes such as senile plaque and neurofibrillary tangles were more marked in this cases than in the cases of DLBD. Furthermore a large number of cortical Lewy bodies were found in the cases of DLBD, but few in this case. The distribution and number of Lewy bodies did not correspond with those of senile changes in the cases of DLBD. Also the cerebral cortical structure was better preserved in the cases of DLBD than in this case. In conclusion, from the clinicopathological findings, we considered that this case is Alzheimer's disease associated with Parkinson's disease. According to Kosaka's study, this case seemed to correspond with a transitional type of the Lewy body disease.

Aged↗

Left main coronary artery disease. Clinical and angiographic features. A retrospective study regarding two groups of patients with left main coronary artery disease and three-vessel disease.

BACKGROUND: The aim of this study was to assess the ability of clinical and instrumental features to identify patients with left main coronary artery disease (LMCD) compared with a three-vessel coronary artery disease group. METHODS: A cohort of 70 patients with LMCD was matched with another one of 66 patients with three-vessel disease. A history of angina before angiography was similar in both groups; the higher degrees of stable angina and the forms of unstable angina were moderately prevalent in the group with LMCD. RESULTS: In the last subgroup a significantly reduced incidence of previous acute myocardial infarction (AMI) was observed (p < 0.05). The resting electrocardiogram (ECG) showed higher incidence of atrial fibrillation (fa) and left bundle branch block (BBS) in the subjects with LMCD, with a statistic value (p < 0.05). The exercise test performed by a lot of patients appeared equally positive for inducible ischemia in the 2 groups. Significantly higher exercise peak load was achieved by the patients with three-vessel disease (p < 0.05). The coronary angiography showed a prevalence of right dominant circulation in the 2 groups; significantly the collateral circulation was more represented in the subjects with three-vessel disease (p < 0.05). Most patients with LMCD underwent a bypass coronary artery graft surgery (CABG surgery) more frequently than the ones with three-vessel disease (p < 0.01). In the former group the cardiovascular mortality within an average 2-year follow-up proved higher as to the latter group even if without statistic significance. CONCLUSIONS: Nevertheless this retrospective study showed some limitations. Particularly the incidence of clinical and instrumental variables and their capacity to differentiate LMCD patients from those with three-vessel disease were not demonstrated.

Acute Disease↗

The quantitative measurement of autoantibodies to thyroglobulin and thyroid peroxidase by automated microparticle based immunoassays in Hashimoto's disease, Graves' disease and a follow-up study on postpartum thyroid disease.

The aim of this study was to investigate the association between various autoimmune thyroid diseases and the presence of anti-TPO and anti-Tg antibodies using two novel automated microparticle based immunoassays developed for the AxSYM analyzer. Serum samples from 65 individuals with Hashimoto's Disease, 38 with Graves' Disease and 80 UK blood donors were assayed. In addition, samples were taken from 50 women known to be positive for TPO antibodies, for up to 24 weeks following delivery. Precision for both assays ranges from 5.7-9.1% CV, while analytical sensitivity was determined to be 1.0 IU/ml for Anti-Tg and 0.3 IU/ml for Anti-TPO. The Anti-TPO test showed positive results in 86% of Hashimoto's Disease and 87% of Graves' Disease. The figures obtained for Anti-Tg were 58% and 73% respectively. Specificity was 94% with Anti-TPO and 99% with Anti-Tg. The postpartum women were divided into 2 groups, group A remained symptomless while group B developed thyroid dysfunction. Within the 2 groups, medians calculated at each time point were compared between and within groups using the Mann-Whitney Rank Sum Test or the Kruskal-Wallis One Way ANOVA on Ranks. Anti-TPO baseline levels (week 6) were statistically different between both groups (median 36 vs. 167 IU/ml, p = 0.002). In group A, the median values increased from 36 to 87 IU/ml within the observation period, although the difference was not statistically significant. In group B, antibody titres showed a statistically significant increase from 168 IU/ml (week 6) up to 676 IU/ml after 20 weeks (p < 0.001). Anti-Tg baseline levels were not statistically different between the two groups. In group A, the median values did not change significantly over time (range: 47-86 IU/ml) whereas antibody titres in group B showed a statistically significant increase from 79 IU/ml (week 6) to 276 IU/ml after 24 weeks (p = 0.002). Results obtained indicate that these assays provide useful tools for the quantitative determination of autoantibodies in both primary diagnosis as shown with the Hashimoto's disease and Graves' disease samples and patient follow-up as demonstrated with the postpartum samples. The automation and high precision of the assays make them perfectly suited to routine diagnostic use.

Autoanalysis↗

Association of celiac disease with connective tissue diseases and autoimmune diseases of the digestive tract.

Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten in susceptible individuals, and is one of the most frequent genetically based diseases, with a prevalence of 1:200 in the general population. The association between CD and connective tissue diseases (CTD) and autoimmune diseases of the digestive tract (DT) has been described in several case reports but in few extensive studies, with varying prevalence. A high rate of false positive results were observed when low specific tests, such as the anti-gliadin and the guinea pig tissue transglutaminase (tTG) antibody assays were used. In a study of 400 patients with CTD and 218 with autoimmune DT disease, tested for IgA and IgG anti-tTG using the more specific human recombinant antigen, 12 cases (1.9%) of anti-tTG antibody positivity were found, but only 2 (0.3%) were confirmed as affected by CD following small bowel biopsy. Most of the patients testing false positive had primary biliary cirrhosis. In this short review we describe the association between CD and CTD, inflammatory bowel disease and primary biliary cirrhosis, with special emphasis on the diagnostic accuracy of CD antibody assays.

Animals↗

Analysis of cardiovascular disease and kidney outcomes in multidisciplinary chronic kidney disease clinics: complex disease requires complex care models.

PURPOSE OF REVIEW: Chronic kidney disease is recognized as being highly prevalent in the population, and associated with morbidity and mortality relative to the general population. The complexity of patients and the multiplicity of interventions required to maintain health has forced clinicians to develop different models of healthcare delivery. This publication reviews the current literature on specific interventions to reduce progression of chronic kidney disease and cardiovascular disease, and studies the examination of outcomes of patients exposed to different healthcare delivery models. Specifically we examine the rationale and outcomes of those seen in multidisciplinary clinics. RECENT FINDINGS: Current evidence supports the use of rennin-angiotensin system blockers, reduction of blood pressure and proteinuria and phosphate control. Additional less robust studies support the need for attention to anemia, hyperparathryoidism, and other more "kidney specific" risk factors. The attendance of identified chronic kidney disease patients at multidisciplinary clinics appears to improve survival once dialysis is started. Despite aggressive management, not all patients are able to meet clinical targets associated with improved outcomes. SUMMARY: The recognition of the complexity of chronic kidney disease care and the need to develop and test models of care in addition to the single interventions is a challenge for both researchers and clinicians. Current data support the use of multidisciplinary clinics in improving outcomes of referred patients. Future research will help to refine and define appropriate care models for this growing chronic kidney disease population.

Calcium↗

[Quality of life assessment in Inflammatory Bowel Disease (IBD): German version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D; disease-specific instrument for quality of life assessment) -- first application and comparison with international investigations].

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome-parameter in health research and care. The aim of the working group Quality of Life in the Competence Network Inflammatory Bowel Disease (IBD; in the original German: "Kompetenznetz chronisch entzündliche Darmerkrankungen") is to generate instruments for assessment of HRQOL and its implementation as standards in clinical trials, health care and research in IBD. METHODS: The Inflammatory Bowel Disease Questionnaire (IBDQ) is an international validated disease specific instrument for HRQOL-assessment. A German version of the IBDQ was elaborated and tested in 415 outpatients with Crohn's disease (CD, n = 306) and ulcerative colitis (UC, n = 109). The aim of the study was to compare the results of HRQOL-assessment (IBDQ-D) with international investigations, to correlate HRQOL results with disease activity and to preform a pretest of psychometric properties. RESULTS: International data suggest that the IBDQ-D is a suitable instrument for HRQOL-assessment in CD and UC. For both disease a statistically significant negative correlation with disease activity was found. Tested psychometric properties do not suggest that a revision of the IBDQ-D is required. The IBDQ-D offers the HRQOL-assessment as an primary or secondary outcome in clinical trials in IBD in Germany.

Adult↗

Ultrastructural evaluation of activated forms of microglia in human brain in selected neurological diseases (SSPE, Wilson's disease and Alzheimer's disease).

Activated forms of microglia were ultrastructurally evaluated in three neurological diseases of different aetiology (subacute sclerosing panencephalitis--SSPE, Wilson's disease and Alzheimer's disease). The occurrence of activated rod, ramified and amoeboid microglia was found in the investigated diseases. The widest ultrastructural variability of microglia was in SSPE, including the presence of mitotic chromosomes or centrioles in its cytoplasm, which indicates microglia proliferation. In the nuclei of activated microglia, some nuclear bodies with different structures were frequently seen, whereas lamellar structures (similar to developing Birbeck's bodies--pathognomonic to Langerhans-type dendritic cells) were observed in the cytoplasm. The activated forms of microglia with apoptotic features were found only in SSPE cases. Some apoptotic nuclei were filled with nucleocapsids of measles virus. In Alzheimer's disease, activated microglia was most frequently bound to senile plaques. Ramified microglia was in contact with amyloid fibrils, which penetrated its cytoplasm and reached the nuclear membrane and channels of rough endoplasmic reticulum, or was situated among dystrophic neurites. Rod microglia was found predominantly at the edge of senile plaques. In Wilson's disease, the ultrastructure of activated microglia showed mostly indirect forms between rod, ramified and amoeboid microglia. The microglia ultrastructure suggests that its morphological form may express functional involvement in the pathogenesis of a given disease entity.

Adolescent↗

Early undifferentiated connective tissue disease. IV.Musculoskeletal manifestations in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of patients with well-established connective tissue diseases: followup analyses in patients with unexplained polyarthritis and patients with rheumatoid arthritis at baseline.

OBJECTIVES: To examine the musculoskeletal manifestations in a large cohort of patients (n = 410) diagnosed with either a well-established connective tissue disease (CTD) (n = 197) or an early undifferentiated CTD (n = 213) with a symptom duration of <1 year. This study was aimed at determining the predictive value of demographic, clinical, and laboratory features on outcome in patients with unexplained polyarthritis (UPA) (from the early undifferentiated CTD cohort; n = 67) or rheumatoid arthritis (RA) (from the well-established CTD cohort; n = 57), over a 5-year followup period. METHODS: Patients from both cohorts were assessed at years 1, 3, and 5. At the study visits, clinical data were collected in a standardized manner, and sera were obtained and stored. A priori criteria were established for patient ascertainment and diagnosis over the duration of the study. Standard statistics were used for comparisons of baseline characteristics in patients diagnosed as having systemic lupus erythematosus, RA, undifferentiated CTD, and UPA at entry into the cohorts. Baseline features in patients with UPA were examined according to the different subsequent outcomes (RA, CTD, or undifferentiated CTD, remission [nonpersistent], or persistent or active UPA). Baseline features in patients with RA whose disease remained active versus those in whom remission was attained were also examined. Two multivariable analyses, classification trees and polychotomous logistic regression, were performed to predict disease outcomes over time. RESULTS: The overall rate of ascertainment for the 410 patients ranged from 90 % at year 1 to 71 % at year 5. Patients with established CTDs showed a tendency for more stable diagnoses than those with early undifferentiated CTDs (90-100% versus 45-70%). Consistent baseline predictors of persistent active disease among patients with RA, in both univariate and multivariable analyses, were higher joint counts for pain and tenderness and higher erythrocyte sedimentation rate (ESR). In approximately 20% of patients who were classified as having RA when they originally entered the cohort, the disease was in remission at 5 years. Twenty percent of the patients originally classified as having UPA developed RA over the duration of the study. These patients tended to be older and to have swelling of small joints at baseline. However, a consistent pattern of predictive variables could not be identified in the multivariable analyses, other than at year 1 (higher small joint counts for swelling and higher ESR). CONCLUSION: Baseline features (joint counts, and ESR) among RA patients were variously predictive of persistently active disease at years 1-5. Consistent baseline predictors of outcome among patients with UPA only emerged at year 1. Remission occurred in approximately 20% of RA patients, whereas a similar percentage of patients with UPA developed RA. These findings have implications with regard to treatment decisions in patients with early RA and/or UPA.

Adult↗

Frequent occurrence of non-specific gliadin antibodies in chronic liver disease. Endomysial but not gliadin antibodies predict coeliac disease in patients with chronic liver disease.

BACKGROUND: The frequency of gliadin antibody (GA) positivity has been found to be increased among patients with chronic liver disease, as has that of coeliac disease (CD). CD has also been found to be increased among patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). METHODS: To investigate these relationships further, a micro-enzyme-linked immunosorbent assay and immunofluorescence tests for GAs and endomysial antibodies (EMAs) were performed in large subgroups of patients representing various chronic liver diseases and in healthy blood donors. RESULTS: As compared with blood donors (among whom it was 5%) the frequency of IgA GA positivity was higher in all patient subgroups: alcoholic liver disease, 20% (22 of 110, P < 0.001); PBC, 16% (16 of 101, P < 0.001); PSC, 24% (19 of 80, P < 0.001); chronic hepatitis, 19% (13 of 70, P < 0.001); and hepatitis C virus infection, 11% (11 of 104, P < 0.01). Two patients with autoimmune chronic hepatitis were EMA-positive, and in both cases the presence of CD was verified by small-bowel biopsy. CONCLUSIONS: IgA GA positivity generally occurs at increased frequency among patients with chronic liver disease and may represent non-specific immune activation. In liver disease GA testing is not useful in screening for CD, whereas the EMA test seems to be highly specific. CD is more prevalent than expected among patients with autoimmune chronic hepatitis but not among those with PBC or PSC.

Adult↗