Do the pleiotropic effects of statins have a clinical significance?

The effectiveness of statins in the treatment of hypercholesterolaemia and the reduction in cardiovascular risk have now been clearly demonstrated. While their beneficial effects on the reduction of atherosclerosis and its clinical manifestations occur mainly due to the reduction in LDL-cholesterol, some pleiotropic actions which are independent of LDL-cholesterol have frequently been put forward in recent years. In effect, an improvement in endothelial function (increased vasodilatation in particular), an in vitro reduction in smooth muscle cell proliferation, a reduction in thrombosis, promotion of fibrinolysis and positive effects on atheromatous plaque stabilisation have been observed. Elsewhere, some anti-oxidant and anti-inflammatory properties have been attributed to statins. However, many of the described 'pleiotropic' effects are not due to the direct action of statins, but occur with the reduction in LDL-cholesterol. Furthermore, certain in vitro effects only occur at much higher than therapeutic doses. These considerations have therefore caused doubt about the clinical significance of the statins' pleiotropic effects. Finally, analysis of the results of human clinical trials on statins have proved that their effectiveness relies on the reduction in LDL-cholesterol and that the pleiotropic effects do not actually have a clinical implication.     

Do age-associated changes in 'physiologic' autoantibodies contribute to infection,atherosclerosis, and Alzheimer's disease?

More than 25 years ago, Pierre Grabar proposed that the age-associated increase in serum autoantibodies reflected a homeostatic function of the immune system that defended the internal milieu by targeting senescent molecules and cells for elimination. This mini-review examines recent evidence that autoantibodies may influence the risk of the elderly developing infectious, atherosclerotic, or Alzheimer's disease. Auto-anti-idiotypic antibodies suppress the antibody response to the nominal antigen and, thus, may contribute to the increased risk of infection and poor response to vaccines in the elderly. In contrast, low levels of autoantibodies to oxidised low-density lipoproteins or to the amyloid beta peptide may contribute to the increased risk of developing atherosclerosis of Alzheimer's disease, respectively.     

Do clinical factors help to predict disease course in inflammatory bowel disease?

While therapeutic strategies able to change the natural history of the disease are developing,it is of major importance to have available predictive factors for aggressive disease to try and target these therapeutic strategies.Clinical predictors have probably been the most broadly studied.In both Crohn's disease(CD) and ulcerative colitis(UC),age at diagnosis,disease location and smoking habit are currently the strongest predictors of disease course.A younger age at onset is associated with more aggressive...     

Do depressive symptoms predict Alzheimer's disease and dementia?

BACKGROUND: Depressive symptoms are common in seniors and may predict dementia. The objective of this study was to evaluate multiple measures of depressive symptoms to determine whether they predict subsequent Alzheimer's disease (AD) or dementia. METHODS: This population-based cohort study with 5-year follow-up included 766 community-dwelling seniors (ages 65+ years) in Manitoba, Canada. Measurements considered were the Center for Epidemiologic Studies Depression (CES-D) scale, participant-reported medical history, and duration of depression. RESULTS: Total CES-D score was a significant predictor of AD and dementia when categorized as a dichotomous variable according to the cutoff scores of 16 and 17; a CES-D cutoff of 21 was a significant predictor of AD and a marginally significant predictor of dementia. When analyzed as a continuous variable, CES-D score was marginally predictive of AD and dementia. Neither participant-reported history of depression nor participant-reported duration of depression was significant in predicting AD or dementia. CONCLUSION: Because depressive symptoms as measured by the CES-D predict the development of AD and dementia over 5 years, clinicians should monitor their older patients with these symptoms for signs of cognitive impairment.     

Do intersections of mortality-rate and survival functions have significance?

Common points of intersections have frequently been reported among members of families of linearized mortality-rate and survival functions. A general condition for the existence of such intersections is derived. It is shown that a common point of intersection between straight-line functions exists if and only if the intercepts of the functions are linearly related to their slopes. This slope-intercept condition is applied to a didactic model to illustrate its generality and to three models, the Gompertz-Makeham, the Weibull, and the logistic, which are often used in the analysis of mortality data. The slope-intercept condition for the Gompertz-Makeham mortality-rate model proves to be the well-known Strehler-Mildvan correlation. Families of mortality-rate functions or of the corresponding survival functions but not both may display common points of intersection. Differences between the ages at which survival functions intersect and those at which the associated mortality-rate functions intersect are calculated to be of the order of magnitude of 10 to 20 years. Survival function intersections lie close to the limit of human life span but often arise in consequence of unsupported extrapolations of data obtained at younger ages. These and other results lead to the conclusion that, in themselves, the intersections of survival and mortality-rate functions are not of great importance. To the extent that significance can be attributed to the intersections, it lies in the existence of linear relationships between their slopes and intercepts.     

Anticardiolipin antibodies in chronic viral hepatitis. Do they have clinical consequences?

Antiphospholipid antibodies are a heterogeneous group of acquired autoantibodies that react with anionic phospholipids, such as cardiolipin. Anticardiolipin antibodies (ACAs) are frequently found in patients with systemic lupus erythematosus and other autoimmune disorders and can react with the phospholipid alone or bound to the cofactor beta2-glycoprotein-I. This latter form of cofactor-dependent ACAs is strongly associated with the occurrence of thrombotic events. ACAs have been observed to occur in both chronic hepatitis B and chronic hepatitis C as well as in other viral infections and in neoplastic diseases. In viral infection, ACAs are generally cofactor independent and may represent an epiphenomenon of the infection. Some studies, however, have found an increased incidence of thrombotic disorders in patients with chronic hepatitis C virus (HCV) who manifest ACA positivity suggesting that the presence of these autoantibodies may predispose to thrombosis in specific HCV-infected patients. In conclusion, ACAs are commonly found in patients with chronic viral infection but their pathogenetic role and the mechanisms that stimulate their production have not yet been clarified.     

Tumor cell contamination in re-infused stem cell autografts: does it have clinical significance?

Tumor cells frequently contaminate autologous stem cell products in patients having a variety of malignancies. Mobilized peripheral blood stem cells may be less contaminated with tumor cells than bone marrow harvests are, but they are still frequently infiltrated. Gene-marking studies using retroviral vectors provide evidence that tumor cells contained in autografts contribute to relapse in myeloid leukemia and neuroblastoma patients. Also clinical studies have shown that tumor cell contamination of autografts is associated with shortened disease-free survival; on the other hand, successful ex vivo purging of tumor cells is associated with superior clinical outcome. However, the presence of tumor cells in autografts or insufficient purging may correlate with the extent of systemic residual disease and/or tumor chemosensitivity; therefore, there is no direct evidence that reinfused tumor cells alone cause relapse. Particularly in patients having highly chemosensitive disease and no detected systemic residual disease following high-dose transplant chemotherapy, the relative number of tumor cells contained in autografts and eventually reinfused, may become a determining factor for clinical outcome. There are no randomized trials showing improved (disease-free) survival with purging. In the absence of such trials, the contribution of tumor cells in the stem cell autografts to subsequent relapse remains controversial.     

Cerebral white matter changes and geriatric syndromes: is there a link?

Cerebral white matter lesions (WMLs), also called "leukoaraiosis," are common neuroradiological findings in elderly people. WMLs are often located at periventricular and subcortical areas and manifest as hyperintensities in magnetic resonance imaging. Recent studies suggest that cardiovascular risk factors are associated with the development of WMLs. These lesions are associated with different geriatric syndromes such as falls, executive cognitive impairment, depressive symptoms, and urinary incontinence. Damage to associative pathways in frontal and subcortical regions due to hypoperfusion may disrupt frontal executive, motor control, and other systems, resulting in these manifestations. WMLs are associated with substantial disability and should not be considered a benign and silent condition as once believed. Interventions addressing cardiovascular risk factors should be undertaken in early or mid-life in order to prevent late-life functional impairment associated with WMLs. After these lesions develop and impair executive cognitive functions, the patient's ability to comply with a complex risk reduction program may be significantly compromised.     

Treatment of chronic pain in osteoarthritis: Do opioids have a clinical role?

Pain is the most prominent symptom and clinical finding in osteoarthritis (OA). Acetaminophen and nonsteroidal anti-inflammatory drug (NSAID) therapy are the mainstays of OA analgesia, but other drug and non-drug therapy, joint injections, and surgery may be needed to provide reasonable quality of life. Regularly scheduled, low-dose opioids can produce good relief of chronic nonmalignant pain including pain caused by OA. This paper reviews the potential risks and benefits of opioids, the evidence supporting their use in OA pain, and guidelines for their use in OA pain.     

Does type of disease matter? Gender differences among Alzheimer's and Parkinson's disease spouse caregivers

PURPOSE OF STUDY: Mental health outcomes are widely reported among spouse caregivers, with wives generally faring worse than husbands. We hypothesized that gender differences would not be as strong in a cognitively intact group because caring for cognitively intact spouses may involve less severe reciprocity losses. We also examined gender differences in coping strategies within each group. DESIGN AND METHOD: 175 spouse caregivers for patients with Alzheimer's disease (AD; n = 88) and Parkinson's disease (PD; n = 87) were interviewed. Participants completed perceived stress (PSS), depression (CES-D), state anxiety (STAI, Form Y), and coping strategies (WCCL-R) measures. RESULTS: Wives in the AD group reported significantly worse mental health outcomes than husbands, while wives and husbands in the PD group showed no differences. AD caregiving wives were less likely than husbands to use problem-focused coping strategies. There were no significant gender differences in either group for social support or emotion-focused coping. IMPLICATIONS: Loss of reciprocity in marital relationships may affect women more negatively than men. Future studies that address underlying mechanisms of gender differences and focus on similar caregiving situations and contexts deserve attention.     

Plasma phosphorylated-tau181 levels reflect white matter microstructural changes across Alzheimer’s disease progression.

Metabolic Brain Disease - Alzheimer’s Disease (AD) is characterized by cognitive impairments that hinder daily activities and lead to personal and behavioral problems. Plasma...     

Analysis of tumor morphology in metastatic colorectal cancer: does this classification have any clinical significance?

Background: Macroscopic classification of metastatic liver tumors has been recommended to predict patient prognosis. Methods: We examined the morphological analysis of metastatic colorectal cancer in 64 patients who underwent hepatic resection and the relationship with clinicopathologic factors. To identify the irregularity of the tumor, we calculated three formulas: (1) actual area of representative cut surface of tumor/circular length of tumor margin, (2) actual area of representative cut surface of tumor/elliptic area, defined by the major and minor axes, and (3) deviation of radius of marginal curvature. Results: Following Yasui's macroscopic classification, the values of formulas (1) and (2) in confluent nodules were significantly lower than those in simple nodules (P < 0.05), while the value of formula (3) in confluent nodules was significantly greater than that in simple nodules (P < 0.05). Only a lower value of formula (1) (less than 0.19) was significantly associated with postoperative recurrence (P < 0.05) and a lower value tended to be associated with a shorter disease-free survival after hepatectomy, but not significantly (P = 0.09). However, most values were not associated with any clinicopathologic factors or postoperative survival. Conclusions: We conclude that differences in the morphological irregularity of liver tumors in metastatic colorectal cancer do not have clinical significance. Received: November 12, 2001 / Accepted: March 22, 2002 Acknowledgments. We gratefully acknowledge the helpful mathematical analyses provided by Professor T. Sugawara, from the Department of Education, Nagasaki University, Nagasaki, Japan. Reprint requests to: A. Nanashima     

Do young patients have different clinical presentation of colorectal cancer causing delay in diagnosis?

Purpose

The incidence of colorectal cancer is increasing among young patients. In these patients, colorectal cancer is believed to have a poorer prognosis because it is more aggressive and diagnosed at later stages; however, the behavior of these tumors in young patients remains to be elucidated. We investigated the impact of time interval between onset of symptoms and diagnosis (TISD) at the pathologic stage of colorectal cancer in young patients.

Methods

The medical records of 215 patients with colorectal adenocarcinoma were reviewed. Patients were divided into two groups according to age. The young group (age?<?50 years) consisted of 66 patients, and the older group (age?≥?50 years) of 149 patients. Clinical variables, TISD, pathologic stage, operative mortality, and oncologic outcomes were compared between groups.

Results

The older group had less abdominal pain (74.0 vs. 56.0 %, p?=?0.0129). In multivariate analysis, the following variables were independently associated with tumor pathologic stage: personal history of inflammatory bowel disease (p?<?0.0001), family history of familial adenomatous polyposis (p?=?0.00100), and smoking (p?=?0.0070). Both groups had similar rates regarding pathologic stage (I, 15 vs. 22 %; II, 22 vs. 24 %; III, 27 vs. 16 %; IV, 37 vs. 38 %, p?=?0.3380). There was no difference in overall survival [45 (69 %) vs. 84 (61 %), p?=?0.2482] and cancer-free survival [36 (63 %) vs. 83 (62 %), p?=?0.9218] between groups.

Conclusions

Young patients with colorectal cancer had clinical and pathological presentation similar to that of older patients.