Negative D-dimers and exclusion of venous thromboembolism--own experience

The assessment of D-dimer concentration has become essential step during diagnostic algorithm of venous thromboembolism (VTE). This test characterizes high sensitivity but limited specificity. Negative D-dimer with high probability excludes VTE. The aim of this study was to assess the percentage of patients treated in Department of Internal Medicine, Endocrinology and Haemostatic Disorders, Medical University of Gdańisk, who in spite of clinical signs of VTE showed normal D-dimer level. Between 2000 and 2004 in our department 57 cases with recent deep vein thrombosis (DVT) were diagnosed, in 2 cases with co-existence of pulmonary embolism (PE). The D-dimer concentration was assessed in patients' plasma with the use of immunoturbidometry. Between 57 cases with VTE, 7 patients (12%) showed normal D-dimer level (<500 microg/ml). This group consisted of 4 men and 3 women, aged from 40 to 82 years (the mean age of 58 years). In all 7 cases DVT was diagnosed, in 2 patients with concomitent PE. The final diagnosis was confirmed by compression ultrasonography and pulmonary scintigraphy. Our analysis underlines the observation that occurrence of VTE and negative d-dimer concentration is possible and may probably be related to methodological limitations. However, the lack of increase of D-dimer could also be caused by fibrinolysis alteration.     

Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway

Nonalcoholic fatty liver disease (NAFLD) is a serious health problem. Although NAFLD represents a form of lipotoxicity, its pathogenesis remains poorly understood. The aim of this study was to examine the cellular mechanisms involved in free fatty acid (FFA)-mediated hepatic lipotoxicity. FFA treatment of liver cells resulted in Bax translocation to lysosomes and lysosomal destabilization with release of cathepsin B (ctsb), a lysosomal cysteine protease, into the cytosol. This process was also partially dependent on ctsb. Lysosomal destabilization resulted in nuclear factor kappa B-dependent tumor necrosis factor alpha expression. Release of ctsb into the cytoplasm was also observed in humans with NAFLD and correlated with disease severity. In a dietary murine model of NAFLD, either genetic or pharmacological inactivation of ctsb protected against development of hepatic steatosis, liver injury, and insulin resistance with its associated "dysmetabolic syndrome." In conclusion, these data support a lipotoxic model of FFA-mediated lysosomal destabilization.     

Cost of care of arterial hypertension and its impact on the budget assigned to health in Mexico

OBJECTIVE: To assess the medical care costs of hypertension and their impact on the health care expenditures and on Mexico's Gross National Product (GNP). MATERIAL AND METHODS: An ecological study was conducted from June to November 1999, at Instituto Mexicano del Seguro Social (Mexican Institute of Social Security, IMSS), in Monterrey, Nuevo Leon, Mexico. A random sample of medical charts of patients with hypertension was selected, to extract data on utilization of health services and unitary costs per care episode. The cost per care episode and per hypertensive patient was calculated by adjusting the unitary cost as a function of standard and extreme utilization of IMSS health services. The resulting figure was then projected to the total population of hypertensive patients and compared to the annual health care expenditures of Mexico. RESULTS: The annual cost per patient with hypertension was $1,067 in the standard scenario and $3,913 in the extreme scenario. The annual expenditures from hypertension corresponded to 13.95% of the budget allocated to health care and to 0.71%, of Mexico's GNP. These figures changed to 51.17% and 2.61% in the extreme scenario, respectively. CONCLUSIONS: The costs of hypertension medical care account for a good portion of healthcare resources. This problem should be analyzed by multidisciplinary health teams in search of more efficient medical care alternatives.     

Rapid regression of psoriasis in a coeliac patient after gluten-free diet. A case report and review of the literature

BACKGROUND: Several skin disorders are present in patients affected by coeliac disease (CD) - among them, psoriasis has been described. However, at present the relationship between CD and psoriasis remains controversial since there are few and contrasting data on this topic. METHOD: Here we describe a case of psoriasis in a CD patient not responding to specific therapies for psoriasis. RESULT: The regression of skin lesions after gluten-free diet (GFD) was evident in a short time. CONCLUSION: The present case supports the association between CD and psoriasis and the concept that psoriasis in CD patients can be improved by GFD. Future studies are needed to clarify the possible mechanisms involved in this association.     

Angiotension-converting enzyme gene I/D polymorphism in patients with angina and normal coronary arteriograms

A polymorphism of the human angiotensin-converting enzyme (ACE) gene has been identified in which the insertion (I) rather than the deletion (D) variant is associated with lower circulating and tissue ACE activity. ACE I allele is associated with resistance and endurance performance. Skeletal muscle metabolic efficiency is reduced in patients with heart failure and is improved by ACE inhibition. Profound muscle fatigue is a predominant and debilitating symptom in a proportion or patients with angina and normal coronary arteriograms (ANCA), and we postulated that the gene D allele might be associated with the presence of fatigue in ANCA patients. We studied 33 consecutive patients with typical ANCA who completed a validated fatigue questionnaire, and found an excess of the D allele frequency in patients with the highest fatigue scores compared to those with the lowest (64% vs. 36%; p=0.027).     

Switch from ritonavir-boosted to unboosted atazanavir guided by therapeutic drug monitoring

Plasma concentration of atazanavir (ATV) may be reduced when coadministered with tenofovir (TDF) or proton pump inhibitors. Boosting ATV exposure with ritonavir (r) may make it possible to overcome these drug interactions. However, jaundice and loss of the metabolic advantages of ATV are more frequent using ATV/r than ATV alone. Herein, we assessed whether therapeutic drug monitoring (TDM) could make it possible to identify the subset of patients in whom removal of ritonavir could be attempted without risk of suboptimal plasma ATV exposure and subsequent virological failure. A total of 56 patients with undetectable plasma HIV-RNA under a stable triple regimen containing ATV 300/100 mg qd were switched to ATV 400 mg qd. Plasma ATV concentrations were measured using a reliable high-performance liquid chromatography method. Median plasma ATV C(min) fell from 880 to 283 ng/ml (p = 0.03) after removal of ritonavir. While all patients on ATV/r showed ATV plasma concentrations within therapeutic values (IC(min) above 150 ng/ml) before switching, four patients (7%) fell below this threshold after switching to ATV 400 mg qd. However, only one of this group experienced virological failure at week 24 of follow-up. TDF was part of the antiretroviral regimen in all four cases. From a total of 29 (52%) patients on ATV/r showing grade 3-4 hyperbilirubinemia, only 7 (12%) remained on it upon switching to ATV 400 mg qd (p < 0.001). Patients with complete viral suppression under ATV/r 300/100 mg qd may benefit from switching to ATV 400 mg qd guided by TDM, which may make it possible to minimize adverse events without compromising antiviral efficacy in most cases.     

An exploratory pilot study on the involvement of APOE,HFE, C9ORF72 variants and comorbidities in neurocognitive and physical performance in a group of HIV-infected people

Metabolic Brain Disease - Cognitive decline of aging is modulated by chronic inflammation and comorbidities. In people with HIV-infection (PWH) it may also be affected by HIV-induced inflammation,...     

Neighborhood Blight,Stress, and Health: A Walking Trial of Urban Greening and Ambulatory Heart Rate

We measured dynamic stress responses using ambulatory heart rate monitoring as participants in Philadelphia, Pennsylvania walked past vacant lots before and after a greening remediation treatment of randomly selected lots. Being in view of a greened vacant lot decreased heart rate significantly more than did being in view of a nongreened vacant lot or not in view of any vacant lot. Remediating neighborhood blight may reduce stress and improve health.Vacant lots are abandoned parcels of urban land that signal blight, with overgrown vegetation, trash dumping, and other illegal activities. Exposure to these lots is associated with negative health outcomes.1–7 Although complex social and economic factors broadly explain the relationship between neighborhood blight and health, limited experimentation with biological outcomes has been conducted in real-world settings.8The body’s stress response is a reasonable biological pathway for understanding the impact of neighborhood blight on health.9,10 Although this response is protective in acute situations, permanent downstream inflammatory changes and dysregulation of cardiovascular, neurological, and endocrine systems accumulate over a lifetime for persons repeatedly exposed to stressors in their neighborhood surroundings.11–16 Basic structural improvements to blighted neighborhood environments, such as “greening” vacant lots, offers a promising and sustainable, yet underused, solution to such stressors.5,17We examined the microspatial impact of neighborhood physical conditions during short neighborhood walks by experimentally testing a specific condition (the remediation of blighted vacant land) to a dynamic biological marker (heart rate).18–21 Using georeferenced heart rate monitoring in an experimental study of an individual’s native environment is a unique approach to field studies of neighborhood blight on acute stress.22