Proinflammatory cytokines in acute myocardial infarction with and without cardiogenic shock

BACKGROUND: Inflammatory response is an important feature of acute coronary syndromes and myocardial infarction (MI). The prognostic value of proinflammatory cytokines in patients with acute MI complicated by cardiogenic shock is unknown. METHODS AND RESULTS: In 41 patients admitted with acute MI (age 60 +/- 11 years, six females, 19 Killip class IV) serial plasma concentration of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1Ra) were measured. Seven patients with cardiogenic shock (CS) developed a systemic inflammatory response syndrome (SIRS). Patients with CS-particularly those who developed SIRS-showed significantly higher cytokine levels than patients with uncomplicated MI. In patients with CS and SIRS peak levels of IL-1Ra were 223,973 pg/ml, IL-6 252.8 pg/ml and TNF-alpha 7.0 pg/ml. In CS without SIRS IL-1Ra levels were 19,988 pg/ml, IL-6 109.3 pg/ml and TNF-alpha 3.8 pg/ml. In uncomplicated MI peak IL-1Ra levels were 1,088 pg/ml, IL-6 34.1 pg/ml and TNF-alpha 2.6 pg/ml. CONCLUSIONS: The inflammation-associated cytokines TNF-alpha, IL-6 and IL-1Ra are significantly elevated in patients with MI complicated by CS when compared to patients with uncomplicated MI. Among shock-patients IL-1Ra levels are promising diagnostic markers for early identification of patients developing SIRS, heralding a poor outcome.     

Can public-private collaboration promote tuberculosis case detection among the poor and vulnerable?

Private-public mix (PPM) DOTS is widely advocated as a DOTS adaptation for promoting progress towards the international tuberculosis (TB) control targets of detecting 70% of TB cases and successfully treating 85% of these. Private health care plays a central role in health-care provision in many developing countries that have a high burden of TB. It is therefore encouraging that PPM projects are being set up in various countries around the world to explore possible interaction between the national TB programmes and other partners in the fight against TB. The objective of this review was to use the published literature to assess the range of providers included in PPMs for their ability to provide case-detection services for the vulnerable. From a case-detection perspective, we identify the essential elements of a pro-poor PPM model, namely, cost-effectiveness from a patient perspective, accessibility, acceptability and quality. The review revealed that a very large part of the total spectrum of potential PPM-participating partners has not yet been explored; current models focus on private-for-profit health-care providers and non-governmental organizations. We conclude that it is important to think critically about the type of private providers who are best suited to meeting the needs of the poor, and that more should be done to document the socioeconomic status of patients accessing services through PPM pilots.     

Can Malawi’s poor afford free tuberculosis services? Patient and household costs associated with a tuberculosis diagnosis in Lilongwe

OBJECTIVE: To assess the relative costs of accessing a TB diagnosis for the poor and for women in urban Lilongwe, Malawi, a setting where public health services are accessible within 6 kilometers and provided free of charge. METHODS: Patient and household direct and opportunity costs were assessed from a survey of 179 TB patients, systematically sampled from all public and mission health facilities in Lilongwe. Poverty status was determined from the 1998 Malawi Integrated Household Survey (MIHS). FINDINGS: On average, patients spent US$ 13 (MK 996 or 18 days' income) and lost 22 days from work while accessing a TB diagnosis. For non-poor patients, the total costs amounted to 129% of total monthly income, or 184% after food expenditures. For the poor, this cost rose to 248% of monthly income or 574% after food. When a woman or when the poor are sick, the opportunity costs faced by their households are greater. CONCLUSION: Patient and household costs of TB diagnosis are prohibitively high even where services are provided free of charge. In scaling up TB services to reach the Millennium Development Goals, there is an urgent need to identify strategies for diagnosing TB that are cost-effective for the poor and their households.     

Decreased Beta-adrenoreceptor responsiveness as related to age, blood pressure, and plasma catecholamines in patients with essential hypertension

The role of the sympathetic nervous system as it relates to adrenoreceptor-mediated hemodynamic responses was investigated in patients with essential hypertension and in normal subjects of similar age. An age-related increase in plasma norepinephrine (PNE) concentrations observed in 36 recumbent normal subjects (r = 0.623, p less than 0.001) was not found in 56 patients; the latter included some young patients with high values. Sympathetic overactivity in patients (n = 24) as compared with normotensive subjects (n = 20) was suggested by a greater increase in PNE upon standing (242 +/- 34 vs 155 +/- 25 pg/ml (SEM), p less than 0.05) and persistently higher plasma epinephrine (PE) concentrations at rest and during equieffective exercise (p less than 0.05). In patients, PNE was directly related to systolic (r = 0.57, p less than 0.01) and diastolic (r = 0.53, p less than 0.01) blood pressure. Older age was associated with diminished exercise tachycardia and increased blood pressure responses to exercise, which were both more pronounced in hypertensive patients. This higher pressure/lower heart rate pattern was paralleled by an age-related decrease in isoproterenol sensitivity in normal subjects (0.97 +/- 0.15 in six below age 34 years, 1.31 +/- 0.30 in eight between 35--49 years, and 1.82 +/- 0.12 microgra/m2 in six above 50 years), which was also more pronounced (p less than 0.05) in hypertensive patients (1.20 +/- 1.18 in seven below age 34 years, 2.42 +/- 0.30 in nine between 35--49 years, and 6.73 +/- 2.44 micrograms/m2 in eight above 50 years). Thus, an increase in the patients' blood pressure and age is associated with a progressive reduction in beta-adrenoreceptor sensitivity and/or reactivity. Defective beta-adrenoreceptor-mediated responses may result in unopposed alpha-adrenoreceptor-mediated vasoconstriction and thereby contribute to the development of hypertension.     

Management of patients with nonvariceal upper gastrointestinal hemorrhage before and after the adoption of the Rockall score, in the Italian Gastroenterology Units

OBJECTIVES: Nonvariceal upper gastrointestinal hemorrhage is a frequent reason for ordinary hospital admission. In Italy the use of prognostic scores to stratify the risk has not been adequately validated: the impact on clinical management of a rating system like the Rockall score remains to be established. RING is a 'register' that has been collecting hospital discharge files from hospital gastroenterology units, giving a broad picture of the patients admitted for this pathology. METHODS: We analyzed the hospital discharge files collected between 2001 and 2005 from 12 gastroenterology units, which issued more than 26,000 hospital discharge files for ordinary hospital admission and have been using the Rockall score for defining nonvariceal upper gastrointestinal hemorrhage since 2003. RESULTS: There were 2832 hospital discharge files with a main diagnosis of nonvariceal upper gastrointestinal hemorrhage: 1335 'before' the Rockall score was introduced, 1497 'after' the introduction. Patients' mean age was 67.7+/-16.7 years, with a male/female ratio of 1.7 and no significant changes over the years. There were no differences in the distribution of diagnoses in nonvariceal upper gastrointestinal hemorrhage patients before/after the introduction of the Rockall score, though the mean hospital stay became shorter (7.1+/-5.0 vs. 6.3+/-4.5 days), and mortality declined (2.8 vs. 2.3%), in parallel with the caselist as a whole. For 1102 ordinary hospital admission Rockall score was calculated. Diagnoses were more accurate: significantly fewer undefined causes and an increase in peptic ulcer. The mean Rockall score was 4.6+/-2.2: 17.8% low (0-2), 48.7% intermediate (3-5), and 33.5% high (>or=6). Mean hospital stay, rebleeding, and mortality were correlated with the severity of the score. CONCLUSION: The Rockall score enables the clinician to formulate a more precise diagnosis and substantially shortens the time in hospital, especially for patients at low-risk of rebleeding and death, so more resources can be dedicated to critically ill patients.     

Long-range spatial integration across contrast signs: a probabilistic mechanism?

It is widely assumed that the integration of orientation contrast across spatial gaps within the long-range regime is not selective to the contrast sign of the individual stimuli. Probabilistic models of perceptual integration, however, suggest that long-range spatial integration should be, if not selective, at least sensitive to local contrast signs. To clarify this issue, we tested predictions of a model based on conditional probabilistic weights of identical and opposite contrast signs in a simple spatial configuration of two co-linear lines. Contrast detection thresholds of the target line presented either by itself (control condition) or simultaneously with the co-linear inducer (test condition) were measured. The contrast sign of targets and inducers was varied so that all four possible combinations of signs were produced in the test conditions: (1) dark target with dark inducer, (2) dark target with bright inducer, (3) bright target with bright inducer and (4) bright target with dark inducer. The contrast intensity (Weber ratio) of dark and bright inducers was identical. The coaxial distance between target and inducer was constant in each of two experiments, testing for two distances that corresponded to an angular separation within the long-range domain of spatial integration as defined previously. It is found that targets and inducers with identical contrast signs produce significantly stronger facilitating effects on detection than stimuli with opposite signs. The data closely match predictions consistent with those of a probabilistic model of line contrast integration across spatial gaps and contrast signs within the long-range regime.     

Whiplash-associated disorders impairment rating: neck disability index score according to severity of MRI findings of ligaments and membranes in the upper cervical spine

The aim of this study was to explore whether reported pain and functional disability in whiplash-associated disorders (WAD) patients is associated with lesions to specific soft tissue structures in the upper cervical spine, as assessed by MRI. Pre-selected structures for MRI assessment included the alar ligaments, the transverse ligament, the tectorial and the posterior atlanto-occipital membranes. The questionnaire employed was a modification of the Oswestry Low Back Pain Index. It was comprised of ten single items related to pain and activity of daily living. Ninety-two whiplash patients and 30 control persons, randomly drawn, were included. WAD patients reported significantly more pain and functional disability than the controls, both for total score and each of the ten single items. In the WAD patients, MRI lesions to the alar ligaments showed the most consistent association to the reported pain and disability. Lesions to other structures often occurred in combination with lesions to the alar ligaments. Lesions to the transverse ligament and to the posterior atlanto-occipital membrane also appeared to be related to the NDI score, although the association was weaker than for the alar ligament. The disability score increased with increasing number of abnormal (grade 2-3) structures. These results indicate that symptoms and complaints among WAD patients can be linked with structural abnormalities in ligaments and membranes in the upper cervical spine, in particular the alar ligaments.