199 research outputs found
Pneumomediastinum: a rare complication of anorexia nervosa in children and adolescents. A case study and review of the literature
Spontaneous pneumomediastinum is uncommon in paediatric practice. We describe two cases of spontaneous pneumomediastinum in a child and an adolescent with anorexia nervosa. Thorough investigation failed to reveal any underlying cause for secondary pneumomediastinum. Pneumomediastinum in anorexia nervosa can be caused by not only elevated intrathoracic pressures, but also by the poor quality of the alveolar walls due to malnutrition. The incidence of spontaneous pneumomediastinum in anorexia nervosa is probably higher than that recorded, since it resolves spontaneously and, therefore, it can remain undetected. We conclude that it is our considered opinion that malnutrition associated with anorexia nervosa predisposes for spontaneous pneumomediastinum due to weakness of the alveolar wall and the loss of connective tissue
Prevalence of suspected hypertrophic cardiomyopathy or left ventricular hypertrophy based on race and gender in teenagers using screening echocardiography
BACKGROUND:The goal of this study was to evaluate the prevalence of suspected hypertrophic cardiomyopathy (HCM) in a population of teenagers undergoing screening echocardiography for the detection of HCM.METHOD:The Anthony Bates Foundation performs screening echocardiography for the prevention of sudden death. A total of 2,066 students were studied between the ages of 13 to 19 years. Suspected HCM was defined as any wall thickness greater than or equal to] 15 mm. LVH was defined as wall thickness greater than or equal to] 13 mmRESULTS:Prevalence of suspected HCM was 0.7% (14/2066). After adjusting for hypertension (HTN), the total prevalence was 0.5% (8/1457). In a subgroup analysis, 551 teenagers with documented race and LV wall thickness were identified between the ages of 13 - 19 years. African American teenagers 6% (3/50)] had higher prevalence of suspected HCM 0.8% (4/501), OR 7.93, CI 1.72-36.49, p = 0.002]. After multivariate adjustment for age, gender, BMI and HTN (systolic BP >140 and diastolic BP of > 90), African American race remained independently associated with suspected HCM (OR 4.89, CI 1.24-39.62, p = 0.02).CONCLUSION:The prevalence of suspected HCM in young teenagers is approximately 0.2%. This prevalence appears to be higher in African Americans. However, due to small number of African Americans in our population, our result needs to be confirmed in larger trials.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]
Antithrombotic therapy and survival in patients with malignant disease
A broad range of studies suggest a two-way relationship between cancer and venous thromboembolism (VTE). Patients with cancer have consistently been shown to be at elevated risk for VTE; this risk is partly driven by an intrinsic hypercoagulable state elicited by the tumour itself. Conversely, thromboembolic events in patients without obvious risk factors are often the first clinical manifestation of an undiagnosed malignancy. The relationship between VTE and cancer is further supported by a number of trials and meta-analyses which, when taken together, strongly suggest that antithrombotic therapy can extend survival in patients with cancer by a mechanism that extends beyond its effect in preventing VTE. Moreover, accumulating evidence from in vitro and in vivo studies has shown that tumour growth, invasion, and metastasis are governed, in part, by elements of the coagulation system. On 22 May 2009, a group of health-care providers based in the United Kingdom met in London, England, to examine recent advances in cancer-associated thrombosis and its implications for UK clinical practice. As part of the discussion, attendees evaluated evidence for and against an effect of antithrombotic therapy on survival in cancer. This paper includes a summary of the data presented at the meeting and explores potential mechanisms by which antithrombotic agents might exert antitumour effects. The summary is followed by a consensus statement developed by the group
Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.
OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock.
METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact.
RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring.
CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock
Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections
Background: Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly cross-reactive for serologically distinct influenza A virus subtypes. However, it is not clear to what extent such pre-existing cellular immunity can provide cross-subtype protection against novel emerging influenza A viruses. Methodology/Principal: Findings We show in the mouse model that naturally occurring sequence variations of the conserved nucleoprotein of the virus significantly impact cross-protection against lethal disease in vivo. When priming and challenge viruses shared identical sequences of the immunodominant, protective NP366/Db epitope, strong cross-subtype protection was observed. However, when they did not share complete sequence identity in this epitope, cross-protection was considerably reduced. Contributions of virus-specific antibodies appeared to be minimal under these circumstances. Detailed analysis revealed that the magnitude of the memory CD8 T cell response triggered by the NP366/Db variants was significantly lower than those triggered by the homologous NP366/Db ligand. It appears that strict specificity of a dominant public TCR to the original NP366/Db ligand may limit the expansion of cross-reactive memory CD8 T cells to the NP366/Db variants. Conclusions/Significance: Pre-existing CD8 T cell immunity may provide substantial cross-protection against heterosubtypic influenza A viruses, provided that the priming and the subsequent challenge viruses share the identical sequences of the immunodominant, protective CTL epitopes
Pre-hospital ECG for acute coronary syndrome in urban India: A cost-effectiveness analysis
<p>Abstract</p> <p>Background</p> <p>Patients with acute coronary syndrome (ACS) in India have increased pre-hospital delay and low rates of thrombolytic reperfusion. Use of ECG could reduce pre-hospital delay among patients who first present to a general practitioner (GP). We assessed whether performing ECG on patients with acute chest pain would improve long-term outcomes and be cost-effective.</p> <p>Methods</p> <p>We created a Markov model of urban Indian patients presenting to a GP with acute chest pain to compare a GP's performing an ECG versus not performing one. Variables describing the accuracy of a GP's referral decision in chest pain and ACS, ACS treatment patterns, the effectiveness of thrombolytic reperfusion, and costs were derived from Indian data where available and other developed world studies. The model was used to estimate the incremental cost-effectiveness ratio (ICER) of the intervention in 2007 US dollars per quality adjusted life years (QALY) gained.</p> <p>Results</p> <p>Under baseline assumptions, the ECG strategy cost an additional 1124/QALY. All results indicated the intervention is cost-effective under current World Health Organization recommendations.</p> <p>Conclusions</p> <p>While direct presentation to the hospital with acute chest pain is preferable, in urban Indian patients presenting first to a GP, an ECG performed by the GP is a cost-effective strategy to reduce disability and mortality. This strategy should be clinically studied and considered until improved emergency transport services are available.</p
Drug Discovery for Duchenne Muscular Dystrophy via Utrophin Promoter Activation Screening
Background: Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. Methodology/Principal Findings: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. Conclusions/Significance: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics an
A review of bronchiolitis obliterans syndrome and therapeutic strategies
Lung transplantation is an important treatment option for patients with advanced lung disease. Survival rates for lung transplant recipients have improved; however, the major obstacle limiting better survival is bronchiolitis obliterans syndrome (BOS). In the last decade, survival after lung retransplantation has improved for transplant recipients with BOS. This manuscript reviews BOS along with the current therapeutic strategies, including recent outcomes for lung retransplantation
The gender specific frequency of risk factor and CHD diagnoses prior to incident MI: A community study
BACKGROUND: CHD is a chronic disease often present years prior to incident AMI. Earlier recognition of CHD may be associated with higher levels of recognition and treatment of CHD risk factors that may delay incident AMI. To assess timing of CHD and CHD risk factor diagnoses prior to incident AMI. METHODS: This is a 10-year population based medical record review study that included all medical care providers in Olmsted County, Minnesota for all women and a sample of men residing in Olmsted County, MN with confirmed incident AMI between 1995 and 2000. RESULTS: All medical care for the 10 years prior to incident AMI was reviewed for 150 women and 148 men (38% sample) in Olmsted County, MN. On average, women were older than men at the time of incident AMI (74.7 versus 65.9 years, p < 0.0001). 30.4% of the men and 52.0% of the women received diagnoses of CHD prior to incident AMI (p = 0.0002). Unrecognized and untreated CHD risk factors were present in both men (45% of men 5 years prior to AMI) and women (22% of women 5 years prior to first AMI), more common in men and those without a diagnosis of CHD prior to incident AMI (p < 0.0001). CONCLUSION: A CHD diagnosis prior to incident AMI is associated with higher rates of recognition and treatment of CHD risk factors suggesting that diagnosing CHD prior to AMI enhances opportunities to lower the risk of future CHD events
Genetic approaches to human renal agenesis/hypoplasia and dysplasia
Congenital abnormalities of the kidney and urinary tract are frequently observed in children and represent a significant cause of morbidity and mortality. These conditions are phenotypically variable, often affecting several segments of the urinary tract simultaneously, making clinical classification and diagnosis difficult. Renal agenesis/hypoplasia and dysplasia account for a significant portion of these anomalies, and a genetic contribution to its cause is being increasingly recognized. Nevertheless, overlap between diseases and challenges in clinical diagnosis complicate studies attempting to discover new genes underlying this anomaly. Most of the insights in kidney development derive from studies in mouse models or from rare, syndromic forms of human developmental disorders of the kidney and urinary tract. The genes implicated have been shown to regulate the reciprocal induction between the ureteric bud and the metanephric mesenchyme. Strategies to find genes causing renal agenesis/hypoplasia and dysplasia vary depending on the characteristics of the study population available. The approaches range from candidate gene association or resequencing studies to traditional linkage studies, using outbred pedigrees or genetic isolates, to search for structural variation in the genome. Each of these strategies has advantages and pitfalls and some have led to significant discoveries in human disease. However, renal agenesis/hypoplasia and dysplasia still represents a challenge, both for the clinicians who attempt a precise diagnosis and for the geneticist who tries to unravel the genetic basis, and a better classification requires molecular definition to be retrospectively improved. The goal appears to be feasible with the large multicentric collaborative groups that share the same objectives and resources
- …