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PubMed2006

Medical disease and alcohol use among veterans with human immunodeficiency infection: A comparison of disease measurement strategies.

BACKGROUND: Many people with human immunodeficiency (HIV) infection drink alcohol. We asked whether level of exposure to alcohol is associated with medical disease in a linear or nonlinear manner, whether the association depends upon the proximity of alcohol use, and whether it varies by source used to measure disease (chart review vs. ICD-9 Diagnostic Codes). METHODS: The Veterans Aging 3 Site Cohort Study (VACS 3) enrolled 881 veterans, 86% of all HIV-positive patients seen, at 3 VA sites from June 23, 1999, to July 28, 2000. To maximize the sensitivity for alcohol exposure, alcohol use was measured combining data from patient self-report, chart review, and ICD-9 codes. We assigned the greatest exposure level reported from any source. Alcohol use within the past 12 months was considered current. Data on comorbid and AIDS-defining medical diseases were collected via chart review and ICD-9 diagnostic codes. The association of alcohol use (level and timing) and disease was modeled only for diseases demonstrating > or =10% prevalence. Linearity was compared with nonlinearity of association using nested multivariate models and the likelihood ratio test. All multivariate models were adjusted for age, CD4 cell count, viral load, intravenous drug use, exercise, and smoking. RESULTS: Of 881 subjects enrolled, 866 (98%) had sufficient data for multivariate analyses, and 876 (99%) had sufficient data for comparison of chart review with ICD-9 Diagnostic Codes. Of the 866, 42 (5%) were lifetime abstainers; 247 (29%) were past drinkers; and 577 (67%) were current users. Among the 824 reporting past or current alcohol use, 341 (41%) drank in moderation, 192 (23%) drank hazardously, and 291 (35%) carried a diagnosis of abuse or dependence. ICD-9 codes showed limited sensitivity, but overall agreement with chart review was good for 15 of 20 diseases (kappa > 0.4). The following diseases demonstrated a > or =10% prevalence with both measures (hepatitis C, hypertension, diabetes, obstructive lung disease, candidiasis, and bacterial pneumonia). All of these were associated with alcohol use (P < 0.05). Hepatitis C, hypertension, obstructive lung disease, candidiasis, and bacterial pneumonia demonstrated linear associations with level of alcohol use (P < 0.03). Past alcohol use increased the risk of hepatitis C and diabetes after adjustment for level of exposure (P < 0.01). With the exception of candidiasis, the associations between level and timing of alcohol use were similar when measured by ICD-9 codes or by chart review. CONCLUSIONS: Past and current use of alcohol is common among those with HIV infection. Estimates of disease risk associated with alcohol use based upon ICD-9 Diagnostic Codes appear similar to those based upon chart review. After adjustment for level of alcohol exposure, past use is associated with similar (or higher) prevalence of disease as among current drinkers. Finally, level of alcohol use is linearly associated with medical disease. We find no evidence of a "safe" level of consumption among those with HIV infection.

Alcohol Drinking↗

PubMed1999

The prevalence of gallstone disease in a defined cohort of patients with Crohn's disease.

OBJECTIVE: Crohn's disease (CD) is associated with a high prevalence of gallstone disease but the relative risk has not been completely established. Ileal disease or resection have been considered as contributing factors to the increased risk. The aim of this study was to evaluate the prevalence of gallstone disease in a defined cohort of CD patients, to evaluate possible risk factors, and to evaluate the relative risk compared with the general population. METHODS: All inhabitants in Stockholm County born in 1933-1935 or 1953-1955, with CD diagnosed between 1955-1989 and not having had a previous cholecystectomy, were invited for an ultrasonography of the gallbladder. The prevalence of gallstone disease was related to disease extent, previous intestinal resections, age, and gender. The relative risk of developing gallstones was calculated using a recent study of gallstone disease in general, with similar age groups as controls. RESULTS: We found that 26.4% had gallstone disease (relative risk [RR] = 1.8; 95% confidence interval [CI], 1.2-2.7). The number of previous intestinal resections was the only significant risk factor. There was no significant difference in gallstone disease between gender (28.2% vs 24.1%) or age (34% vs 21.8%). CONCLUSIONS: Patients with Crohn's disease, regardless of gender and age, have almost a doubled risk of developing gallstone disease compared with the general population. Circumstances related to laparotomy may contribute to the increased risk. The lack of association between the disease extent and the site of previous intestinal resection, together with a previous finding of normal cholesterol saturation of the bile in patients with CD, indicate that these patients may develop pigment stones rather than cholesterol stones.

Adult↗

PubMed2002

Psychological disorder and severity of inflammatory bowel disease predict health-related quality of life in ulcerative colitis and Crohn's disease.

OBJECTIVE: The determinants of health-related quality of life in inflammatory bowel disease are not completely understood. The present study aimed to assess two factors in patients with inflammatory bowel disease: a) whether health-related quality of life is independently associated with both bowel disease severity and psychological disorder, and b) whether Crohn's disease is associated with more marked psychological disorder than ulcerative colitis. METHODS: 116/170 (68%) consecutive patients with inflammatory bowel disease attending a GI clinic (37 patients with ulcerative colitis, 75 patients with Crohn's disease, and four unspecified) completed the following self-report questionnaires: demographic details, a modified disease activity index, a total severity measure, the Hospital Anxiety and Depression Scale, and the Short Form-36. RESULTS: Thirty patients (25.9%) scored 11 or more on either the depression or anxiety subscales of the Hospital Anxiety and Depression Scale indicating probable psychological disorder; 55% (47.4%) scored over 8 indicating possible psychological disorder. Stepwise multiple regression analyses showed that both psychological symptoms and disease severity or activity contributed independently to impaired health-related quality of life. After severity of disease was taken into account, there were no significant differences between Crohn's disease and ulcerative colitis in terms of depression scores and health-related quality of life. CONCLUSIONS: The presence of psychological disorder in inflammatory bowel disease contributes to poor health-related quality of life, regardless of the severity of the condition. Detection and treatment of psychological disorder in inflammatory bowel disease carries the potential to improve health-related quality of life for these patients.

Adult↗

PubMed1998

Ultrastructural localization of cell junctional components (desmoglein, plakoglobin, E-cadherin, and beta-catenin) in Hailey-Hailey disease, Darier's disease, and pemphigus vulgaris.

The distribution of desmoglein, plakoglobin, E-cadherin, and beta-catenin in the peri-lesional and lesional skin of Hailey-Hailey disease, Darier's disease, and pemphigus vulgaris was examined by immunoelectron microscopy. In the peri-lesional skin, the immunolabeling of these desmosomal components was localized to desmosomes. Adherens junction-associated E-cadherin and beta-catenin were at the cell periphery, excluding desmosomes. The labeling pattern was similar among these diseases, but the labeling intensity particularly that of plakoglobin in Hailey-Hailey disease and Darier's disease, was less than that of normal controls, suggesting that these glycoproteins are quantitatively less concentrated in the normal epidermis of these inherited diseases. In the acantholytic cells of Hailey-Hailey disease and Darier's disease the immunolabeling of the components of desmosomes was diffusely distributed in the cytoplasms, whereas that of adherensjunction was mostly at the cell periphery and partly diffusely in the cytoplasm. In contrast, desmosomes of detaching keratinocytes in pemphigus vulgaris still showed the labeling of desmoglein and plakoglobin. These findings suggest that the inherited acantholytic diseases, i.e., Hailey-Hailey disease and Darier's disease have a different pathogenesis from that of autoimmune acantholysis in pemphigus vulgaris: The intracellular components of desmosomes may primarily be disrupted in the genetic acantholytic diseases in the initial stages of acantholysis. Several unsolved questions in the previous light microscopic immunofluorescence studies using the same antibodies are now answered: 1) the diffusion of desmosomal proteins is not due to the internalization of desmosomes, 2) intracellular components of adherens junction are also finally dissolved, 3) diffuse cytoplasmic immunofluorescence patterns of desmosomal components could be explained by immunoelectron microscopy as those attached to cell membrane and trapped in tonofilament aggregates.

Cadherins↗

PubMed1993

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.

Celiac Disease↗

PubMed2004

Pediatric Crohn's disease and growth retardation: the role of genotype, phenotype, and disease severity.

BACKGROUND: Delayed growth is a well-established feature of pediatric Crohn's disease. Several factors have been shown to affect growth, including disease location, severity, and treatment. The recently discovered NOD2 gene has been correlated to ileal location of Crohn's disease and subsequently could affect growth through the resulting phenotype or as an independent risk factor. The aim of our study was to determine if growth retardation is affected by genotype independently of disease location or severity. METHODS: Genotyping for 3 NOD2 single-nucleotide polymorphisms was performed in 93 patients with detailed growth records. Parameters including disease location, disease severity, and NOD 2 genotype and their effect on z scores for height and weight at disease onset and during follow-up were analyzed. RESULTS: NOD2 mutations were correlated with ileal location but not with disease severity or growth retardation. Ileal involvement was significantly associated with height retardation at disease onset and the lowest z score during follow-up. Use of steroids affected weight but not height. Regression models for growth variables revealed that the strongest association with impaired growth is with disease severity (weight- and height-failure odds ratios: 6.17 and 4.52, respectively). CONCLUSIONS: Severity of disease is correlated with growth failure for both height and weight. Location of disease is a weaker predictor of disordered growth and is correlated with growth retardation but not growth failure. The NOD2 genotype was not correlated with growth retardation or growth failure.

Child↗

PubMed1997

Doppler sonography evaluation of superior mesenteric artery flow to assess Crohn's disease activity: correlation with clinical evaluation, Crohn's disease activity index, and alpha 1-antitrypsin clearance in feces.

OBJECTIVE: This study was undertaken to investigate the value of Doppler flow measurements of the superior mesenteric artery (SMA) as a marker for disease activity in patients with Crohn's disease. SUBJECTS AND METHODS: Duplex Doppler sonography measurements of SMA blood flow volume were obtained in 29 consecutive patients with suspected Crohn's disease. We prospectively sought a correlation between the independent assessment of Doppler flow measurements and markers for disease activity: Crohn's disease activity index and fecal alpha 1-antitrypsin clearance and our reference standard based on clinical history, physical examination, laboratory values, endoscopy, surgery, and follow-up. RESULTS: In 27 of 29 patients, adequate measurements of SMA blood flow were obtained. In 15 patients no disease activity was judged to be present or no Crohn's disease (n = 2) was found at follow-up (group 1). In 12 patients, activity of Crohn's disease was diagnosed (group 2) on the basis of the reference standard. In group 2 the Doppler SMA blood flow values were significantly higher (p < .05) than those for group 1 (826 +/- 407 ml/min versus 323 +/- 103 ml/min). Of the other parameters investigated, only the alpha 1-antitrypsin value correlated with the reference standard but to a lesser degree than the values for SMA blood flow measurement. CONCLUSION: This prospective study shows that SMA Doppler blood flow measurements can be used to assess disease activity in patients with Crohn's disease. This approach may be of value in the diagnosis and follow-up of patients with Crohn's disease, providing directly available, quantifiable, noninvasive information on disease activity.

Adult↗

PubMed2000

Herd-level risk factors for infection with Mycobacterium paratuberculosis in US dairies and association between familiarity of the herd manager with the disease or prior diagnosis of the disease in that herd and use of preventive measures.

OBJECTIVE: To evaluate associations among herd infection status, herd management practices, and familiarity of the herd manager with Mycobacterium paratuberculosis (Johne's disease) or prior disease diagnosis in that herd to support development of Johne's disease-control programs. DESIGN: Population-based cross-sectional study. SAMPLE POPULATION: 1,004 US dairies, each with > or = 30 cows, representing 79.4% of US dairy cows. PROCEDURE: Questionnaires were administered to dairy managers, and blood samples were collected from cows during herd visits. Sera were tested for antibodies to M paratuberculosis, using a commercially available ELISA. Multivariable logistic regression analyses were used to evaluate associations between use of management practices, herd disease status, and familiarity of the manager with Johne's disease or prior diagnosis of Johne's disease in that herd. RESULTS: Results from serologic testing revealed that 3.4% of cows and 21.6% of dairy herds were infected with M paratuberculosis. Factors associated with infection included number of cows in herd, region of country, percentage of cows born at other dairies, group housing for periparturient cows, and group housing for preweaned calves. Few preventive practices were positively associated with prior diagnosis of Johne's disease (time of separation of newborn calf from dam) or familiarity of the manager with the disease (teats and udder washed before colostrum collected). CONCLUSIONS AND CLINICAL RELEVANCE: Risk factors associated with Johne's disease in this study confirmed those management practices generally recommended for disease control. An educational problem, however, is the finding that herd managers familiar with Johne's disease generally use management practices similar to those used by managers unfamiliar with the disease.

Animals↗

PubMed1996

Is "unilateral" moyamoya disease different from moyamoya disease?

Whether a diagnosis of moyamoya disease is justified in patients with typical angiographic evidence of moyamoya disease unilaterally and normal angiographic findings contralaterally remains controversial. In this study the authors analyzed longitudinal angiographic change, familial occurrence, and basic fibroblast growth factor (bFGF) concentration in the cerebrospinal fluid (CSF) of patients with "unilateral" moyamoya disease. Over a 10-year period, 10 cases of unilateral moyamoya disease were followed using conventional angiography or magnetic resonance angiography. Basic FGF in CSF, obtained from the subarachnoid space of the cerebral cortex during revascularization surgery, was measured in five cases. Among the 10 cases of unilateral moyamoya disease, only one pediatric case showed obvious signs of progression to typical bilateral disease. The other nine cases (including six adults and three children) remained stable throughout follow-up radiological examinations (magnetic resonance angiography) with a mean observation period of 3.5 years. There was no familial occurrence in these cases of unilateral moyamoya disease. Levels of bFGF, which are high in typical moyamoya disease, were low in these patients. The progression from unilateral moyamoya disease to the typical bilateral form of the disease appears to be infrequent. The low levels of bFGF in the CSF of these patients and the lack of familial occurrence strongly suggest that most cases of unilateral moyamoya disease, especially those found in adults, are distinct from typical bilateral moyamoya disease.

Adolescent↗

PubMed2002

Polycystic kidney disease at end-stage renal disease in the United States: patient characteristics and survival.

BACKGROUND: The patient characteristics and mortality associated with autosomal dominant polycystic kidney disease have not been characterized for a national sample of end-stage renal disease (ESRD) patients. METHODS: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy (including patients who eventually received renal transplants) between January 1, 1992 and June 30, 1997 and analyzed in an historical cohort study of polycystic kidney disease. RESULTS: Of the study population, 5,799 (1.5%) had polycystic kidney disease. In logistic regression, polycystic kidney disease was associated with Caucasian race (odds ratio 3.31, 95% CI, 3.09-3.54), women (1.10, 1.04-1.16), receipt of renal transplant (4.15, 3.87-4.45), peritoneal dialysis (vs. hemodialysis, 1.37, 1.27-1.49), younger age, and more recent year of first treatment for ESRD. Use of pre-dialysis EPO but not the level of serum hemoglobin at initiation of ESRD was significantly higher in patients with polycystic kidney disease. Patients with polycystic kidney disease had lower mortality compared to patients with other causes of ESRD, but patients with polycystic kidney disease had a higher adjusted risk of mortality associated with hemodialysis (vs. peritoneal dialysis) compared to patients with other causes of ESRD (hazard ratio 1.40, 1.13-1.75). CONCLUSIONS: Hematocrit at presentation to ESRD was not significantly different in patients with polycystic kidney disease compared with patients with other causes of ESRD. Peritoneal dialysis is a more frequent modality than hemodialysis in patients with polycystic kidney disease, and patients with polycystic kidney disease had an adjusted survival benefit associated with peritoneal dialysis, compared to patients with other causes of renal disease.

Adult↗

PubMed2001

Angiotensinogen mutations and risk for ischemic heart disease, myocardial infarction, and ischemic cerebrovascular disease. Six case-control studies from the Copenhagen City Heart Study.

BACKGROUND: The M235T and T174M angiotensinogen mutations have been linked to increased risk for ischemic heart and cerebrovascular disease. OBJECTIVE: To determine whether angiotensinogen mutations are associated with ischemic heart disease, myocardial infarction, and ischemic cerebrovascular disease. DESIGN: Six case-control studies from the Copenhagen City Heart Study. SETTING: Copenhagen, Denmark. PARTICIPANTS: Participants in the Copenhagen City Heart Study and patients from the same hospital with ischemic heart disease (n = 866 and n = 943, respectively), myocardial infarction (n = 519 and n = 493, respectively), or ischemic cerebrovascular disease (n = 489 and n = 434, respectively) and 7975 controls without these conditions. MEASUREMENTS: Genotypes for the M235T and T174M angiotensinogen mutations were compared between controls and Copenhagen City Heart Study participants with ischemic heart disease, myocardial infarction, and cerebrovascular disease (studies 1a, 1b, and 1c) and patients from Copenhagen University Hospital with the same conditions (studies 2a, 2b, and 2c). RESULTS: Relative allele frequencies of 235T and 174M in the general population were 0.41 and 0.12, respectively. Genotype was not associated with increased risk for ischemic heart or ischemic cerebrovascular disease in studies of either mutation alone or combined in women or men. Among compound heterozygotes (235MT /174TM ), women in case-control study 2a had decreased risk for ischemic heart disease in age-adjusted analysis; however, this decreased risk was not seen in multifactorial-adjusted or matched analyses, in men, or in case-control study 1a. Among double homozygotes (235TT /174MM ), women in case-control study 2b had increased risk for myocardial infarction in matched analysis; however, this increased risk was not seen in age- or multifactorial-adjusted analyses, in men, or in case-control study 1b. Among single homozygotes (235TT /174TT ), men in case-control study 2b had increased risk for myocardial infarction in multifactorial-adjusted and matched analyses. This risk was not present in age-adjusted analysis, in women, or in case-control study 1b. In addition, male single homozygotes had decreased risk for ischemic cerebrovascular disease in case-control study 2c in age- and multifactorial-adjusted analyses, but this finding was not seen in matched analysis, in women, or in case-control study 1c. CONCLUSIONS: In six large case-control studies, the M235T and T174M angiotensinogen mutations were not consistently associated with increased (or decreased) risk for ischemic heart disease, myocardial infarction, or ischemic cerebrovascular disease. Statistically significant associations may represent chance findings rather than real phenomena.

Aged↗

PubMed2000

Occupational diseases in the Czech Republic in the year 1998. The need for unifying European standards/criteria for all occupational diseases.

In the Czech Republic, the Clinics and Departments for Occupational Medicine according to the legislation have the right to recognise occupational diseases. The diagnosis must correspond to the Czech list of occupational diseases, which is similar to the European list of occupational diseases. The exposure, sufficient enough to cause certain occupational disease, must be confirmed by regional industrial hygienists, responsible for hygienic control of the workplace. It is evident that the number of diseases is very much dependent upon the standards/criteria used to recognise occupational diseases. In the Czech Republic, the patients suffering from occupational diseases are given considerable financial compensations, which creates a great motivation for them to apply for occupational diseases. The article presents the overview of occupational diseases in the Czech Republic in the year 1998. The total number of diseases was 2111, the incidence per 100,000 employees was 45.8. It is necessary to present and discuss unifying criteria for occupational diseases in European countries, as well as the minimum level of the damage, that could be called an occupational disease. The criteria should be co-ordinated, because in a unified Europe, there will be many more possibilities for change in the workplace.

Czech Republic↗

PubMed1989

[The incidence of occupational diseases in the health services within the catchment area of the Clinic for Occupational Diseases of the School of Medicine in Prague].

The authors analyzed notified occupational diseases at the department of occupational diseases during the 10 past years, focusing attention on workers in the health workers' union. The highest ratio is that of viral hepatitis (64.8%) and skin diseases (14.7%). These are followed by other infectious diseases, tuberculosis, asthma bronchiale, etc. The largest number of occupational diseases was reported in female health workers (74.7%) which is consistent with nationwide data on occupational diseases. The high ratio of women is not surprising with regard to the marked feminization of this occupation. The highest ratio of occupational diseases was reported in women aged 21-30 years, whereby viral hepatitis accounted for 32.6%. Occupational diseases are important not only from the medical but also from the economic aspect. Therefore even a minor reduction of occupational diseases has marked economic consequences. From the investigation ensues that at present it is important to concentrate above all on two groups of occupational diseases, i.e. occupational infectious contagious diseases and occupational skin diseases. A prerequisite for reduction of type B viral hepatitis is immunization of health workers at risk departments against hepatitis B, which is being implemented at present.

Adult↗

PubMed1996

The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial.

OBJECTIVE: Health-related quality of life (HRQOL) affects outcome in chronic diseases such as inflammatory bowel disease (IBD). The inflammatory bowel disease questionnaire (IBDQ), a disease-specific HRQOL questionnaire, can define changes in health status in IBD, but simple instruments are needed for daily application. The present study proposed to develop a short version of the IBDQ, the SIBDQ, for community physicians. METHODS: Using data from a clinical trial in 149 patients with Crohn's disease, 10 items were selected (by forward stepwise regression) that best explained the variance of the IBDQ or dimensional scores (bowel, systemic, social, emotional). The validity, reliability, and responsiveness of the SIBDQ were then assessed in 150 different patients with Crohn's disease and 45 with ulcerative colitis. All scores were reported with a 7-point scale (1 = poor HRQOL, 7 = optimum HRQOL). RESULTS: Mean SIBDQ scores were similar (p = 0.22) in Crohn's patients among 14 participating centers at study entry. Mean scores were lower in active Crohn's disease (range 4.00-4.92) than inactive disease (range 4.67-5.83; p = 0.0015). In active ulcerative colitis, the mean SIBDQ was 4.79 +/- 1.17 compared to 5.90 +/- 0.80 (p = 0.0006) in inactive disease. The SIBDQ explained 92% and 90% of the IBDQ variance in Crohn's disease and ulcerative colitis, respectively. In patients with stable Crohn's disease, the test-retest reliability coefficient was 0.65 and Crohnbach's alpha was 0.78, indicating good reliability. In patients with Crohn's disease who relapsed during follow-up, the mean SIBDQ decreased by -0.93 + 0.55 (p = 0.001). CONCLUSION: The SIBDQ is valid, reliable, and able to detect meaningful clinical changes in HRQOL that might occur in the office setting.

Adult↗

PubMed2025

Efficacy of Advanced Therapies in Achieving Remission by Disease Location in Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: We compared the efficacy of different advanced therapies by disease location in patients with Crohn's disease (CD) through a systematic review and meta-analysis. METHODS: Through a systematic review, we identified 14 randomized controlled trials in 3139 patients with moderate-to-severe CD who were treated with different advanced therapies vs placebo, and reported efficacy in inducing clinical remission, stratified by disease location (isolated colonic vs ileal disease, excluding ileocolonic disease). We grouped advanced therapies based on the primary mechanism of action: anti-interleukins, Janus kinase inhibitors (JAK inhibitors), anti-integrins, and tumor necrosis factor (TNF) antagonists. We calculated treatment efficacy (drug vs placebo), overall and by drug class, for colonic vs ileal disease. RESULTS: Overall treatment efficacy of advanced therapies vs placebo was higher in patients with colonic (odds ratio [OR], 4.09; 95% confidence interval [CI], 3.02-5.54) vs ileal CD (OR, 1.80; 95% CI, 1.23-2.63; P < .001). By drug class, anti-interleukins demonstrated a higher efficacy in colonic disease (OR, 4.29; 95% CI, 2.77-6.64) vs ileal disease (OR, 2.31; 95% CI, 1.44-3.70; P = .059), whereas no difference in efficacy was observed with anti-integrins (colonic vs ileal: OR, 1.79; 95% CI, 0.55-5.87 vs 2.10; 95% CI, 0.80-5.53; P = .84). For JAK inhibitors, efficacy was observed only in patients with isolated colonic disease (OR, 4.37; 95% CI, 2.67-7.15), but not in ileal disease (OR, 1.01; 95% CI, 0.54-1.89; P < .001). All analyses had minimal to moderate heterogeneity. CONCLUSIONS: The magnitude of efficacy of advanced therapies for ileal CD is generally lower compared with isolated colonic CD, with JAK inhibitors showing particularly limited efficacy for ileal disease. These results may help inform treatment selection.

Humans↗

PubMed1998

Advanced glycation end products in Alzheimer's disease and other neurodegenerative diseases.

Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but A beta negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.

Adult↗

PubMed2004

Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls.

Parkinson's disease is a common neurodegenerative disorder primarily characterized by rigidity, tremor and bradykinesia. Cognitive impairment and neuropsychiatric symptoms are frequent in Parkinson's disease, with a 70% cumulative incidence of dementia. The aim of this cross-sectional study was to establish the pattern of cerebral atrophy on MRI in Parkinson's disease patients with dementia. We used voxel-based morphometry (VBM) to provide an unbiased means of investigating brain volume loss. Whole brain structural T1-weighted MRI scans from Parkinson's disease patients with dementia (PDD, n = 26), Parkinson's disease patients without dementia (n = 31), Alzheimer's disease patients (n = 28), patients with dementia with Lewy bodies (DLB, n = 17) and control subjects (n = 36) were acquired. Images were analysed using SPM99 and the optimized method of VBM. Reduced grey matter volume in PDD patients compared with controls was observed bilaterally in the temporal lobe, including the hippocampus and parahippocampal gyrus, and in the occipital lobe, the right frontal lobe and the left parietal lobe, as well as some subcortical regions. Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects. There was significant grey matter atrophy bilaterally in the occipital lobe of PDD patients compared with Parkinson's disease patients. In addition, significant temporal lobe atrophy, including the hippocampus and parahippocampal gyrus was detected in Alzheimer's disease relative to PDD. No significant volumetric differences were observed in PDD compared with DLB. Thus, Parkinson's disease involves grey matter loss in frontal areas. In PDD, this extends to temporal, occipital and subcortical areas, with occipital atrophy in PDD being the only difference between the two groups. This provides important information about the pattern of cerebral atrophy in Parkinson's disease and PDD.

Aged↗

PubMed2005

The clinical epidemiology of cardiovascular disease in chronic kidney disease.

PURPOSE OF REVIEW: To review recent publications concerning the epidemiology and management of cardiovascular disease in the stages of chronic kidney disease. RECENT FINDINGS: Chronic kidney disease is a state of increased risk for atherosclerotic and cardiomyopathic disease. The mechanisms of cardiovascular disease probably change with the different stages of chronic kidney disease. Both proteinuria and decreased glomerular filtration rate are probably independent cardiovascular disease risk factors, although the impact of the latter is modest. Traditional risk factors are important predictors of cardiovascular disease in chronic kidney disease. Recent randomized controlled trials and cohort studies have supported interventions for smoking cessation, blood pressure control, renin-angiotensin system blockade, the correction of lipid abnormalities, and utilizing antiplatelet agents. Some uraemia-related risk factors predict the development of cardiovascular disease, particularly hypoalbuminaemia, inflammation, anaemia, and homocysteinaemia. However, randomized controlled trials of anaemia correction and of an increased quantity of dialysis were negative. SUMMARY: The role of oxidant stress, divalent ion abnormalities, various lipid abnormalities and other potential factors require further investigation. To determine whether these uraemia-related factors are markers of cardiovascular disease risk or are actually cardiotoxic requires additional randomized controlled trials.

Atherosclerosis↗