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Anemia and cardiovascular disease, hospitalization, end stage renal disease, and death in older patients with chronic kidney disease.

BACKGROUND: Large observational studies examining the association between anemia and "hard" clinical outcomes are rare in patients with chronic kidney disease (CKD). METHODS: We used the General Medicare 5% Denominator Files to identify patients aged 67 years or more with CKD on December 31, 1999. Outcomes in the ensuing 2 years were compared in patients with and those without anemia (entry period, 1998-1999; follow-up period, 2000-2001). RESULTS: Of 41,522 CKD patients identified, 49.0% had claims of anemia diagnosis. The factors associated (p< 0.0001) with anemia included older age, female gender, black race, and all 10 comorbid conditions studied; adjusted odds ratios (ORs) exceeded 1.5 for age 80 years old or older (OR, 1.54 compared to <70 years), for black race (OR, 1.52), and for co-existing diagnoses of congestive heart failure (OR, 1.64), gastrointestinal bleeding (OR, 3.65), and liver disease (OR, 2.16). During the follow-up period, outcome event rates (expressed per 1000 patient-years) were as follows: renal replacement therapy, 23.5; death, 186.4; congestive heart failure, 390.0; atherosclerotic vascular disease, 410.5; and first hospitalization, 552.6. Using proportional hazards modeling, the presence of anemia was associated (p < 0.0001) with the following adjusted hazards ratios: atherosclerotic vascular disease, 1.09; congestive heart failure, 1.14; renal replacement therapy, 2.61 and death, 1.40. CONCLUSION: A diagnosis of anemia is present in nearly half of all patients with CKD, aged 67 years or more, a group at very high risk of cardiovascular disease, hospitalization, end-stage renal disease, and death. Anemia is associated with each of these events.

Aged↗

Raised serum activity of phospholipase A2 immunochemically related to group II enzyme in inflammatory bowel disease: its correlation with disease activity of Crohn's disease and ulcerative colitis.

Calcium dependent phospholipase A2 activity in the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was measured in sera of 39 patients with Crohn's disease, 40 patients with ulcerative colitis, and 40 healthy controls. The phospholipase A2 activity was significantly raised in those sera of the patients with active Crohn's disease and those with moderate and severe ulcerative colitis. The major phospholipase A2 activity derived from the sera was separated into two peaks by reverse phase high performance liquid chromatography. The phospholipase A2 active fractions were immunochemically characterised using specific antibody directed against human group II phospholipase A2 purified from rheumatoid synovial fluid. The results suggest that raised serum phospholipase A2 activity in patients with Crohn's disease and ulcerative colitis was mainly attributed to the two forms of phospholipase A2 immunochemically related to group II enzyme. In patients with Crohn's disease, serum phospholipase A2 activity decreased in parallel with clinical improvement, and correlated with serum C-reactive protein and erythrocyte sedimentation rate. The results suggest that serum phospholipase A2 activity may serve as an additional indicator of disease activity. Serum phospholipase A2 activity in patients with ulcerative colitis tends to increase in relation with endoscopic severity, and may be a more sensitive laboratory index than serum C-reactive protein and erythrocyte sedimentation rate to evaluate disease activity.

Acute Disease↗

Breathing pattern during and after maximal exercise in patients with chronic obstructive lung disease, interstitial lung disease, and cardiac disease, and in normal subjects.

Inspiratory muscle fatigue and pulmonary edema are both known to cause rapid shallow breathing. It has been suggested that exercise tolerance in patients with pulmonary disease and cardiac disease may be limited by the development of inspiratory muscle fatigue and pulmonary edema, respectively, at maximal exercise. If these hypotheses are correct, breathing pattern during recovery from maximal exercise in these patients should be rapid and shallow compared with that during exercise. This study was performed to test these hypotheses. Seven patients with chronic obstructive pulmonary disease (COPD), 8 patients with interstitial lung disease (ILD), 7 patients with cardiac disease (CD) (mitral valve disease or left ventricular dysfunction) and 8 normal (NR) subjects each performed maximal incremental exercise on a cycle ergometer. Exercise breathing pattern was compared with that during recovery by calculating the mean difference in tidal volume (at the same levels of minute ventilation) between exercise and recovery for each subject. Recovery breathing pattern was similar to that during exercise for the COPD, ILD, and NR subjects. In contrast, breathing pattern during recovery was rapid and shallow compared with that during exercise for the CD patients; recovery tidal volume was less than that during exercise for the same level of minute ventilation. The fact that rapid shallow breathing does not develop during recovery from maximal exercise in patients with COPD or ILD suggests that inspiratory muscle fatigue does not limit their exercise tolerance. The relative rapid shallow breathing during recovery from maximal exercise in patients with CD is probably due to the development of pulmonary edema at maximal exercise, but further studies are needed to confirm this.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Autoimmune thyroid disease (Graves' disease and hashimoto's thyroiditis) in two patients with Crohn's disease: case reports and literature review.

An increased prevalence of the association between autoimmune thyroid diseases and ulcerative colitis has been suggested, however, not with Crohn's disease, as only 7 cases of thyroid disease coexisting with Crohn's disease have been reported. Herein, we describe 2 patients with Crohn's disease complicated with Graves' disease or autoimmune thyroiditis, and also review other cases with those complications. Some immunological processes are suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear.

Adult↗

Tubulointerstitial renal diseases of children: pathologic features and pathogenetic mechanisms in Fanconi's familial nephronophthisis, antitubular basement membrane antibody disease, and medullary cyst disease.

The renal lesions of 15 children with tubulointerstitial diseases (TID), originally diagnosed as Fanconi's familial nephronophthisis (FFN), medullary cyst disease (MCD), or antitubular basement membrane (TBM) antibody disease were studied by light, electron, and immunofluorescence microscopy and by peroxidase-antiperoxidase stain for IgG. Kidneys originally considered in all three categories showed similar pathologic findings, with periglomerular fibrosis, interstitial fibrosis and infiltration, TBM thickening, and glomerulopathy. The data suggest that MCD and FFN are not synonyms, but that FFN can lead to medullary cystic disease, as can other tubulointerstitial diseases. Anti-TBM disease appears to be a more frequent cause of TID than is usually recognized. Glomerular involvement in TID may be due to deposition of anti-TBM antibody/TBM antigen complexes.

Autoimmune Diseases↗

Control of communicable diseases; apprehension and detention of persons with specific diseases; transfer of regulations. Food and Drug Administration and Centers for Disease Control and Prevention, HHS. Final rule.

The Secretary of Health and Human Service (the Secretary) is transferring a portion of the Food and Drug Administration (FDA) "Control of Communicable Diseases" regulations to the Centers for Disease Control and Prevention (CDC). In general, these regulations provide the Secretary with the authority to apprehend, detain, or conditionally release individuals to prevent the spread of specified communicable diseases. The regulations implement the provisions of the Public Health Service Act (PHS Act) to prevent the introduction, transmission, or spread of communicable diseases from one State or possession into any other State or possession. CDC will have authority for interstate quarantine over persons, while FDA will retain regulatory authority over animals and other products that may transmit or spread communicable diseases. The Secretary is taking this action to consolidate regulations designed to control the spread of communicable diseases, thereby increasing the agencies' efficiency and effectiveness.

Centers for Disease Control and Prevention, U.S.↗

Protection of chickens against overt clinical disease and determination of viral shedding following vaccination with commercially available Newcastle disease virus vaccines upon challenge with highly virulent virus from the California 2002 exotic Newcastle disease outbreak.

During 2002-2003, exotic Newcastle disease (END) virus caused a major outbreak among commercial and backyard poultry in southern California and adjacent states. The outbreak raised concerns regarding the protective immunity of commercially available vaccines for prevention and control of this virus in poultry. We sought to determine if existing commercial live and inactivated Newcastle disease virus (NDV) vaccines could provide protection against the 2002-2003 END virus, and whether current commercial NDV-vaccination programs for broiler-breeders (BB) and broilers (Br) would protect against END-challenge. In the first experiment, birds received a single dose of either inactivated or live B1-type vaccine at 2 weeks-of-age and were challenged 2 weeks post-vaccination with a lethal dose of END. In the second experiment, a high (10(6.9)EID50/bird) or low (10(3.9)EID50/bird) dose of live B1 was applied to 8-week-old chickens, followed by lethal END challenge. In the third experiment, NDV field-vaccinated commercial BB (65 weeks-of-age) and Br (36 days-of-age) were challenged against END virus. Results indicated that both the live and inactivated vaccines protected against morbidity and mortality and significantly reduced the incidence and viral titers shed from chickens in comparison with sham controls, but did not prevent infection and virus shedding. In addition, both doses of live vaccine protected birds and significantly decreased the number of birds shedding virus. All unvaccinated control chickens challenged with END died within 6 days post-challenge (pc). Protection from disease correlated with the presence of antibody titers (determined by enzyme-linked immunosorbent assay (ELISA) or hemagglutination inhibition (HI)) at day of challenge. Commercial BB were protected from disease and exhibited low incidence and titer of challenge virus shed. In contrast, commercial Br exhibited 66% mortality and shed significantly more virus than the BB birds. These results underscore the need to develop new NDV vaccines and vaccine strategies for use during outbreak situations to protect birds from both disease and infection to reduce virus shedding.

Animals↗

Chronic disease management: treating the patient with disease(s) vs treating disease(s) in the patient.

The treatment of chronic disease is often complicated by the coexistence of multiple medical conditions and by the presence of social and psychological impediments. The needs posed by patients with chronic disease are overwhelming the capacity of the American health care system. Alternative disease management systems that rely on specially trained nurse case managers to implement detailed clinical protocols, including drug algorithms, have shown efficacy in managing chronic medical conditions, singly and in combination. By fostering integration of care across subspecialty and medical-social boundaries, such systems enable treatment of the patient with disease(s), not simply treatment of disease(s) in the patient. Working closely with primary care physicians, often by telephone-mediated interaction with patients, nurse case managers may take an expanded role in meeting the challenges posed by chronic disease.

Case Management↗

Trinucleotide repeats in neurologic diseases: an hypothesis concerning the pathogenesis of Huntington's disease, Kennedy's disease, and spinocerebellar ataxia type I.

Three neurodegenerative diseases, Huntington's disease (HD), Kennedy's disease (hereditary spinobulbar muscular atrophy, SBMA), and type 1 spinocerebellar ataxia (SCA-1) have been found to share a common genetic defect: an unstable region of repeated CAG trinucleotides which are thought to be translated into a polyglutamine moiety. The unstable repeat regions occur near the N-termini of the predicted proteins for HD and SBMA, but the location of the CAG repeat region is not known for SCA-1. Each disease is notable for a relatively circumscribed region of central nervous system pathology, and the lack of predicted similarity of the abnormal proteins makes a common mechanism related to the function of each protein unlikely. In order to reconcile the similar genetic abnormalities with the disparities in phenotypes, we suggest a common thread with regard to the pathogenesis of neuronal death. We hypothesize that the mechanism of neurotoxicity in these diseases occurs not through the production of abnormal proteins, but by the generation of abnormal posttranslational cleavage products. These products, in part consisting of abnormally large polyglutamine moieties, act to disturb the cellular and mitochondrial milieu such that energy metabolism is impaired, rendering specific regions of the nervous system vulnerable, and resulting in the clinical phenotypes of HD, SBMA, and SCA-1. We offer this interpretation of recent genetic findings from a neurobiologic perspective, in addition to suggesting testable hypotheses concerning potential disease mechanisms.

Base Sequence↗

Mammary Paget's disease: evidence of diverse origin of the disease with a subgroup of Paget's disease developing from the superficial portion of lactiferous duct and a discontinuous pattern of tumor spread.

The pattern of spread of intraductal carcinoma associated with mammary Paget's disease has not been well studied. The purpose of this study was to examine the site of origin and the pattern of tumor spread with a three-dimensional view by serial sectioning of the tissue blocks from 19 cases of Paget's disease. Intraductal carcinoma in the superficial portion of the lactiferous ducts was seen in continuity with the overlying epidermis with Paget's disease in all 19 cases. In seven cases that had adequate tissue sampling, five showed a continuous pattern of the intraductal carcinoma within the superficial as well as the deep breast tissue. In the remaining two cases, a portion of benign duct was identified between the intraductal carcinoma in the superficial lactiferous duct and the deep breast tissue. This discontinuous pattern of spread of the intraductal carcinoma was also identified in the foci of carcinoma in deep tissue. In the five cases in which the tumor involved the skin and only the superficial portions of the lactiferous duct, the leading edge of the intraductal carcinoma was seen orientated in the direction of the nipple towards the deep breast tissue. Our study of Paget's disease demonstrated that in addition to tumor spread along the lactiferous ducts from intraductal carcinoma in the deep tissue towards the nipple, there was a group of Paget's disease arising from the nipple. These lesions included: (i) lesions limited to the areolar tissue; and (ii) lesions with intraductal carcinoma involving the duct system in both superficial and deep breast tissue with and, possibly, without skip areas pattern of spread. Although certain cases of Paget's disease may appear superficial, an independent associated carcinoma in deep breast tissue has to be ruled out.

Breast Neoplasms↗

Desmosomal dissolution in Grover's disease, Hailey-Hailey's disease and Darier's disease.

Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non-immune acantholytic diseases; specifically, four cases of Grover's disease (GD), one case of Hailey-Hailey's disease (HHD) and one case of Darier's disease (DD), and these were compared to two cases of immune-mediated acantholytic disease pemphigus vulgaris (PV). The proteins studied included: 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin; 2. The intercellular desmosomal proteins, desmoglein and CD44; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot-like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoantibodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vinculin was intact in GD, HHD and DD, but was lost in PV. This study, our previous work, and that of others, suggest that: 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected; 2. In PV, the intercellular glycoproteins are primarily involved; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.

Acantholysis↗

Economic impact of Alzheimer's disease in the United Kingdom. Cost of care and disease severity for non-institutionalised patients with Alzheimer's disease.

BACKGROUND: While the costs associated with Alzheimer's disease have been shown to be significant, there are few data relating cost of care to severity of the disease. AIMS: We aimed to compare the costs associated with different severities of Alzheimer's disease with those incurred by control subjects over a three-month period. METHOD: In this cross-sectional, multicentre, naturalistic analysis, non-institutionalised patients with Alzheimer's disease (128), their care-givers (128), and 56 matched controls were interviewed once to establish resource use over the previous three months. Patients were stratified into three severity groups according to their Mini Mental State Examination score. Costs were calculated from the perspective of society as a whole. RESULTS: Over the three-month period, total mean cost per control subject (387 Pounds) was minor compared with mean cost incurred by patients with mild (6616 Pounds), moderate (10,250 Pounds) and severe (13,593 Pounds) Alzheimer's disease. Indirect cost, mainly time spent by care-givers, was the main cost component in all groups (68.6%), followed by direct medical costs (24.7%). CONCLUSIONS: The cost of care for an Alzheimer's disease patient is directly related to the severity of the patients illness.

Aged↗

Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm.

Metabolic syndrome patients are at increased risk for developing cardiovascular morbidity and mortality. The increasing prevalence of the metabolic syndrome in various asymptomatic populations has been well documented, however, limited information is available about the prevalence in manifest atherosclerotic vascular disease patients. The aim of this study is to determine the overall and gender-specific prevalence of the metabolic syndrome and its components in these patients. This cross-sectional survey of 1117 patients, aged 18-80 years, mean age 60+/-10 years, comprised patients with coronary heart disease (n=527), cerebrovascular disease (n=258), peripheral arterial disease (n=232) or abdominal aortic aneurysm (n=100). Metabolic syndrome was defined by Adult Treatment Panel III. The prevalence of the metabolic syndrome in the study population was 46%: 58% in PAD patients, 41% in CHD patients, 43% in CVD patients and 47% in AAA patients. Overall, women had a higher prevalence than men (56% versus 43%). Age did not influence the metabolic syndrome prevalence; crude odds ratios (crude OR) 1.00 (95% CI: 0.99-1.02). Our results demonstrate a high prevalence of the metabolic syndrome in patients with manifest atherosclerotic vascular disease. Screening for metabolic syndrome in patients with high risk for new vascular incidents may identify patients with even higher vascular risk and may direct anti-atherosclerotic treatment in order to prevent new vascular incidents in the same or another vascular bed.

Adolescent↗

Risk factors and cardiovascular diseases associated with asymptomatic peripheral arterial occlusive disease. The Limburg PAOD Study. Peripheral Arterial Occlusive Disease.

OBJECTIVES: To describe the risk-factor profile and cardiovascular comorbidity of asymptomatic peripheral arterial occlusive disease (PAOD). DESIGN: A cross-sectional survey. Asymptomatic PAOD was defined as an ankle-brachial pressure index < 0.95, measured on two consecutive occasions, without intermittent claudication. Logistic regression analyses were performed to investigate independent associations between age, gender, smoking status, hypertension, obesity, diabetes, hypercholesterolaemia, physical activity, a family history of cardiovascular disease, the occurrence of ischaemic heart disease and cerebrovascular disease (CeVD) and asymptomatic PAOD. SETTING: 18 general practices in the province of Limburg, the Netherlands. SUBJECTS: A total of 3650 subjects, aged 40-78 years. MAIN RESULTS: Asymptomatic PAOD was present in 8.6% (n = 314) and symptomatic disease in 3.8% (n = 138) of the participants. Age, smoking status, hypertension, and diabetes were significantly associated with asymptomatic PAOD. The ratio of asymptomatic to symptomatic PAOD was higher among the younger age groups. Male gender, hypertension and smoking status were stronger associated with symptomatic PAOD compared with asymptomatic PAOD. Asymptomatic subjects had more IHD and CeVD comorbidity compared with the healthy population. CONCLUSION: Our findings suggest that the risk-factor profile and cardiovascular comorbidity of asymptomatic subjects is comparable to claudicants. Preventive efforts could be made to diminish the influence of especially smoking, diabetes and hypertension in asymptomatic subjects.

Adult↗

Prior bowel resections, perianal disease, and a high initial Crohn's disease activity index are associated with corticosteroid resistance in active Crohn's disease.

OBJECTIVES: Some patients with Crohn's disease (CD) do not respond to corticosteroid therapy. Furthermore, corticosteroids frequently cause side effects. Thus, predictive parameters for treatment refractoriness would be helpful for treatment decisions. METHODS: A total of 300 patients with active CD (i.e., with a Crohn's Disease Activity Index [CDAI] >200) entered the study. Treatment started with 60-100 mg/day prednisolone equivalent, which was then tapered to 10-15 mg/day within 6 wk and maintained at that dose for another 4 wk. After 10 wk of treatment, response to steroids was defined by a CDAI <150, steroid resistance by a CDAI always > or =150 and steroid dependency by a relapse after dose reduction. Of 239 eligible patients, 196 were responders, 26 were steroid resistant, and 17 were steroid dependent. RESULTS: Prior bowel resections, a high initial CDAI, and perianal disease were associated with steroid resistance. Of the steroid resistant patients 53.9% were bowel-resected compared to 20.4% of the responders (relative risk = 3.63; 95% CI = 1.79-7.36). Perianal disease was observed in 42.3% of steroid resistant patients versus 21.9% of responders (relative risk = 2.28; 95% CI = 1.12-4.66) and initial CDAI was 347+/-91 in resistant patients versus 301+/-81 in responders (p < 0.05). Parameters for steroid dependent patients were not significantly different from those of responders. CONCLUSIONS: In this study (thus far the largest study for the evaluation of predictive factors for treatment refractoriness to corticosteroids in CD), only prior bowel resection, perianal disease, and a high initial CDAI were found to be predictive of resistance to steroid treatment.

Adrenal Cortex Hormones↗

A comparison of the onset of protection induced by Newcastle disease virus strain B1 and a fowl poxvirus recombinant Newcastle disease vaccine to a viscerotropic velogenic Newcastle disease virus challenge.

Four-week-old specific-pathogen-free white rock chickens were immunized with either a commercial recombinant fowl poxvirus-vectored Newcastle disease vaccine (FPN) expressing the hemagglutinin-neuraminidase and fusion protein genes of Newcastle disease virus (NDV) strain B1 or live NDV B1. Vaccinates and controls were challenged by eyedrop and intranasal (E/I) route with a viscerotropic velogenic NDV at 14 days postvaccination to determine the time of clearance of challenge virus. In a subsequent experiment, chickens were challenged at 3, 6, or 10 days postvaccination to determine the onset of immunity. Chickens that received a recommended field dose (1x) or a 0.01x dose of FP-N subcutaneously (s.c.) and were seropositive by hemagglutination-inhibition test at 14 days postvaccination cleared the challenge virus by 14 days postchallenge. Clinical Newcastle disease and high challenge virus titers in tissues were seen only in seronegative FP-N 0.01x dose vaccinates and controls. In a comparison of vaccination with FP-N (1x, 10(4,9) median tissue culture infective dose) s.c., B1 (10(6) median egg infective dose [EID50]) s.c., or B1 (10(6) EID50) E/I, chickens vaccinated at 6 or 10 days before challenge with all vaccines were protected against clinical disease, but only those vaccinated with B1 E/I 10 days before challenge were protected against infection with the challenge virus. Vaccination at 3 days before challenge with B1 E/I provided early protection, but severe nervous signs developed later and reduced overall protection to 60%, whereas disease in chickens vaccinated with B1 s.c. and FP-N s.c. 3 days before challenge was similar to the challenge controls.

Animals↗