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Substantial Morbidity (substantial + morbidity)
Selected AbstractsYouth Risk Behavior Surveillance , United States, 2001JOURNAL OF SCHOOL HEALTH, Issue 8 2002Jo Anne Grunbaum ABSTRACT: Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. This report covers data during February-December 2001. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority healthrisk behaviors among youth and young adults; these behaviors contribute to unintentional injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 34 state surveys, and 18 local surveys conducted among students in grades 9,12 during February-December 2001. In the United States, approximately three-fourths of all deaths among persons aged 10,24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2001 national Youth Risk Behavior Survey demonstrated that numerous high school students engage in behaviors that increase their likelihood of death from these four causes: 14.1% had rarely or never worn a seat belt during the 30 days preceding the survey; 30.7% had ridden with a driver who had been drinking alcohol; 17.4% had carried a weapon during the 30 days preceding the survey; 47.1% had drunk alcohol during the 30 days preceding the survey; 23.9% had used marijuana during the 30 days preceding the survey; and 8.8% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 2001, 45.6% of high school students had ever had sexual intercourse; 42.1% of sexually active students had not used a condom at last sexual intercourse; and 23% had ever injected an illegal drug. Two-thirds of all deaths among persons aged ,25 years result from only two causes: cardiovascular disease and cancer. The majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 2001, 28.5% of high school students had smoked cigarettes during the 30 days preceding the survey; 78.6% had not eaten ,5 servings per day of fruits and vegetables during the 7 days preceding the survey; 105% were overweight; and 67.8% did not attend physical education class daily. Health and education officials at national, state, and local levels are using these YRBSS data to analyze and improve policies and programs to reduce priority health-risk behaviors among youth. The YRBSS data also are being used to measure progress toward achieving 16 national health objectives for 2010 and 3 of the 10 leading health indicators. [source] Universal newborn screening and adverse medical outcomes: A historical noteDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2006Jeffrey P. Brosco Abstract Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and genetic conditions. Although the benefits of such screening programs appear to outweigh their costs, some critics have claimed that historical examples of inadvertent harm ensuing from false-positive screening results and subsequent inappropriate medical treatment should make us wary of expanding universal newborn screening. In this essay, we report the results of a review of the published literature to assess whether the extension of screening from at risk populations to all newborns led to substantial morbidity and mortality from misguided medical treatment. We provide a historical overview of universal newborn screening programs in the United States, and then focus on six early NBS programs: congenital hypothyroidism, phenylketonuria, congenital adrenal hyperplasia, galactosemia, sickle cell disease, and maple syrup urine disease. Our comprehensive search of published sources did not reveal a widespread problem of harm ensuing from medical treatment of children with false positive screening test results. © 2006 Wiley-Liss, Inc. MRDD Research Reviews 2006;12:262,269. [source] Lipid-lowering therapy in patients with type 2 diabetes: the case for early interventionDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2008Armin Steinmetz Abstract Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and an increase in the preponderance of small, dense low-density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low-density lipoprotein cholesterol (LDL-C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL-C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision-making when initiating lipid therapy. Copyright © 2008 John Wiley & Sons, Ltd. [source] Risk factors for symptomatic hyponatraemia: the role of pre-existing asymptomatic hyponatraemiaINTERNAL MEDICINE JOURNAL, Issue 3 2007M. Bissram Abstract Background: Hyponatraemia is associated with substantial morbidity and mortality. Identification of the risk factors associated with the development of symptomatic hyponatraemia is important in determining preventive strategies. Methods: A retrospective analysis of the risks factors associated with the development of severe, symptomatic hyponatraemia requiring hospital admission over the past 3 years at our institution was carried out. Results: Forty-seven patients (26 women, 21 men) with a hospital admission serum sodium <134 mmol/L were identified. Of these patients, 31 (65.9%) had associated changes in the mental status that improved with the treatment of the hyponatraemia suggesting causality. The average admission sodium level of this cohort was 118.8 mmol/L. Symptomatic hyponatraemia was associated with volume depletion (32.6%), congestive heart failure (26%), syndrome of inappropriate antidiuretic hormone (26%), thiazide diuretic use (26%) and selective serotonin re-uptake inhibitor use (26%). In 21.7% of cases, the cause was multifactorial (congestive heart failure, syndrome of inappropriate antidiuretic hormone or medication use with volume depletion). In 11% of cases, patients were taking both thiazide diuretics and serotonin re-uptake inhibitors. Most importantly, 70.9% of all patients admitted with symptomatic hyponatraemia had pre-existing hyponatraemia that was untreated and believed to be asymptomatic (P < 0.05). This was the most common risk factor identified. We next investigated the prevalence of presumed asymptomatic hyponatraemia in the outpatient setting. Out of 27 496 patients analysed, 14% had serum sodium levels less than or equal to 134 mEq/L and 4% had values less than 130 mEq/L. Conclusion: Pre-existing asymptomatic hyponatraemia is a common finding and is associated with a high risk for the development of worsening hyponatraemia with altered mental status. [source] The Co-Occurrence of Chronic Diseases and Geriatric Syndromes: The Health and Retirement StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2009Pearl G. Lee MD OBJECTIVES: To analyze the co-occurrence, in adults aged 65 and older, of five conditions that are highly prevalent, lead to substantial morbidity, and have evidence-based guidelines for management and well-developed measures of medical care quality. DESIGN: Secondary data analysis of the 2004 wave of the Health and Retirement Study (HRS). SETTING: Nationally representative health interview survey. PARTICIPANTS: Respondents in the 2004 wave of the HRS aged 65 and older. MEASUREMENTS: Self-reported presence of five index conditions (three chronic diseases (coronary artery disease, congestive heart failure, and diabetes mellitus) and two geriatric syndromes (urinary incontinence and injurious falls)) and demographic information (age, sex, race, living situation, net worth, and education). RESULTS: Eleven thousand one hundred thirteen adults, representing 37.1 million Americans aged 65 and older, were interviewed. Forty-five percent were aged 76 and older, 58% were female, 8% were African American, and 4% resided in a nursing home. Respondents with more conditions were older and more likely to be female, single, and residing in a nursing home (all P<.001). Fifty-six percent had at least one of the five index conditions, and 23% had two or more. Of respondents with one condition, 20% to 55% (depending on the index condition) had two or more additional conditions. CONCLUSION: Five common conditions (3 chronic diseases, 2 geriatric syndromes) often co-occur in older adults, suggesting that coordinated management of comorbid conditions, both diseases and geriatric syndromes, is important. Care guidelines and quality indicators, rather than considering one condition at a time, should be developed to address comprehensive and coordinated management of co-occurring diseases and geriatric syndromes. [source] Geriatric Co-Management of Proximal Femur Fractures: Total Quality Management and Protocol-Driven Care Result in Better Outcomes for a Frail Patient PopulationJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2008Susan M. Friedman MD Hip fractures in older adults are a common event, leading to substantial morbidity and mortality. Hip fractures have been previously described as a "geriatric, rather than orthopedic disease." Patients with this condition have a high prevalence of comorbidity and a high risk of complications from surgery, and for this reason, geriatricians may be well suited to improve outcomes of care. Co-management of hip fracture patients by orthopedic surgeons and geriatricians has led to better outcomes in other countries but has rarely been described in the United States. This article describes a co-managed Geriatric Fracture Center program that has resulted in lower-than-predicted length of stay and readmission rates, with short time to surgery, low complication rates, and low mortality. This program is based on the principles of early evaluation of patients, ongoing co-management, protocol-driven geriatric-focused care, and early discharge planning. This is a potentially replicable model of care that uses the expertise of geriatricians to optimize the management of a common and serious condition. [source] Estimating Hip Fracture Morbidity, Mortality and CostsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2003R. Scott Braithwaite MD OBJECTIVES: To estimate lifetime morbidity, mortality, and costs from hip fracture incorporating the effect of deficits in activities of daily living. DESIGN: Markov computer cohort simulation considering short- and long-term outcomes attributable to hip fractures. Data estimates were based on published literature, and costs were based primarily on Medicare reimbursement rates. SETTING: Postacute hospital facility. PARTICIPANTS: Eighty-year-old community dwellers with hip fractures. MEASUREMENTS: Life expectancy, nursing facility days, and costs. RESULTS: Hip fracture reduced life expectancy by 1.8 years or 25% compared with an age- and sex-matched general population. About 17% of remaining life was spent in a nursing facility. The lifetime attributable cost of hip fracture was $81,300, of which nearly half (44%) related to nursing facility expenses. The development of deficits in ADLs after hip fracture resulted in substantial morbidity, mortality, and costs. CONCLUSION: Hip fractures result in significant mortality, morbidity, and costs. The estimated lifetime cost for all hip fractures in the United States in 1997 likely exceeded $20 billion. These results emphasize the importance of current and future interventions to decrease the incidence of hip fracture. [source] Immunogenicity and safety of a novel liposomal influenza subunit vaccine (INFLUSOME-VAC) in young adultsJOURNAL OF MEDICAL VIROLOGY, Issue 4 2003Arie Ben-Yehuda Abstract Influenza and its complications account for substantial morbidity and mortality among young adults and especially among the elderly. In young adults, immunization provides 70,90% protection, while among the elderly the vaccine may be only 30,40% effective; hence the need for new, more immunogenic vaccines. We compared the safety and immunogenicity of a novel IL-2-supplemented liposomal influenza vaccine (designated INFLUSOME-VAC) with that of a commercial subunit vaccine and a commercial split virion vaccine in young adults (mean age 28 years) in the winter of 1999,2000. Seventy-three healthy young adults were randomly assigned to be vaccinated intramuscularly with the following: a commercial subunit vaccine (n,=,17, group A), INFLUSOME-VAC (n,=,36, group B), and a commercial split virion vaccine (n,=,20, group C). The three vaccines contained equal amounts of hemagglutinin (,15 ,g each) from the strains A/Sydney (H3N2), A/Beijing (H1N1), and B/Yamanashi. INFLUSOME-VAC induced higher geometric mean HI titers and higher-fold increases in HI titers against all three strains, compared with the two commercial vaccines. In addition, seroconversion rates for the A/Sydney and B/Yamanashi strains were significantly higher (P,<,0.05) compared with the split virion vaccine, and significantly higher for the three strains compared with the subunit vaccine (69,97% vs 35,65%, P,,,0.02). Moreover, the anti-neuraminidase response was significantly greater (P,=,0.05) in group B vs group A. INFLUSOME-VAC caused mild local pain at the injection site in a significantly higher proportion of the vaccinees (83%). Thus, INFLUSOME-VAC is an immunogenic and safe vaccine in young adults. J. Med. Virol. 69:560,567, 2003. © 2003 Wiley-Liss, Inc. [source] Tunga penetrans: a stowaway from around the worldJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2007MM Sachse Abstract Tungiasis is a cutaneous ectoparasitic infestation by the female sand flea Tunga penetrans. It is predominantly a health problem in sub-Saharan Africa, the Caribbean, Latin America and South America. However, increasing numbers of returning travellers, immigrants, and adopted children are also affected in non-tropical countries. It is a cause of substantial morbidity, with prevalence rates as high as 76% in certain endemic areas. To date, the early extraction of the flea is still the first line therapy. [source] Tuberculosis in liver transplant recipients: A systematic review and meta-analysis of individual patient data,LIVER TRANSPLANTATION, Issue 8 2009Jon-Erik C. Holty Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894,906, 2009. © 2009 AASLD. [source] Laboratory monitoring of new anticoagulants,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010Donna D. Castellone Maintaining a balance between bleeding and clotting has always been a challenge in treating coagulation disorders. A perturbation in that balance can be associated with substantial morbidity and mortality. As a result, anticoagulant monitoring is extremely important, and inappropriate testing may lead to complications. There are now a variety of new anticoagulant drugs in clinical use including several direct thrombin inhibitors (DTIs), such as argatroban, bivalirudin, and hirudin, as well as a Factor Xa inhibitor, fondaparinux. There are pitfalls associated with some of the currently used laboratory monitoring tests, and newer alternative laboratory monitoring tests have been investigated (Walenga and Hoppensteadt, Semin Thromb Hemost 2004;30:683,695). In addition, laboratory testing can assist with transitioning patients from DTI to warfarin therapy. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source] Factors of complicated grief pre-death in caregivers of cancer patientsPSYCHO-ONCOLOGY, Issue 2 2008Alexis Tomarken Abstract Purpose: Over the past decade, Prigerson and her colleagues have shown that symptoms of ,complicated grief',intense yearning, difficulty accepting the death, excessive bitterness, numbness, emptiness, and feeling uneasy moving on and that the future is bleak,are distinct from depression and anxiety and are independently associated with substantial morbidity. Little is known about complicated grief experienced by family caregivers prior to the death. This study sought to examine differences in caregiver age groups and potential risk factors for complicated grief pre-death. Method: Two hundred and forty eight caregivers from multiple sites nationwide (20,86 years of age) identified themselves as primary caregivers to a terminally ill cancer patient. Each caregiver was interviewed using the following measures: the Pre-Death Inventory of Complicated Grief-Caregiver Version; the Brief Interpersonal Support Evaluation List; the Structured Clinical Interview for the DSM-IV Axis I; the Life Orientation Test-Revised; the SEPRATE Measure of Stressful Life Events; the Covinsky Family Impact Survey; and mental health access questions. Results: The study found that those under 60 years old had higher levels of complicated grief pre-death than caregivers 60 and older (t(246)=2.30, p<0.05). Significant correlations were also found between levels of complicated grief pre-loss and the following psychosocial factors: perceived social support (r=,0.415, p<0.001); history of depression (r=,0.169, p<0.05); current depression (r=,0.158, p<0.05); current annual income (Spearman rho =,0.210, p<0.01); annual income at time of patient's diagnosis (Spearman rho =,0.155, p=0.05); pessimistic thinking (r=0.320, p<0.001); and number of moderate to severe stressful life events (Spearman rho = 0.218, p=0.001). In a multi-variate analysis (R2=0.368), pessimistic thinking (Beta = 0.208, p<0.05) and severity of stressful life events (Beta = 0.222, p<0.05) remained as important factors to developing complicated grief pre-death. Conclusions: These results suggest that mental health professionals who work with caregivers should pay particular attention to pessimistic thinking and stressful life events, beyond the stress of the loved one's illness, that caretakers experience. Additionally, although not reaching significance, mental health professionals should also consider younger caregivers at greater risk for complicated grief pre-loss. Copyright © 2007 John Wiley & Sons, Ltd. [source] Roflumilast: clinical benefit in patients suffering from COPDTHE CLINICAL RESPIRATORY JOURNAL, Issue 4 2010Charlotte Suppli Ulrik Abstract Background and aims:, Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality and is characterised by persistent airway inflammation, which leads to impaired airway function, quality of life and intermittent exacerbations. In spite of recent advances in the treatment of COPD, new treatment options for COPD are clearly necessary. The oral phosphodiesterase-4 (PDE4) inhibitor roflumilast represents a new class of drugs that has shown efficacy and acceptable tolerability in preclinical and short-term clinical studies in patients with COPD. Methods and results:, The available long-term clinical studies reviewed here suggest that the clinical efficacy of roflumilast is likely because of the suppression of airway inflammation and not through bronchodilation. Furthermore, the clinical studies have shown a modest improvement in airway function, including FEV1, and a reduction in frequency and severity of COPD exacerbations, as well as a positive effect on several patient-reported outcomes. The clinical benefit of roflumilast appears to be greatest in patients with more symptomatic and severe disease who experience exacerbations. The most common adverse effects are gastrointestinal events, primarily diarrhoea, nauseas and weight loss. Conclusion:, Roflumilast is beneficial for maintenance treatment of patients with severe and symptomatic COPD and with a history of frequent acute exacerbations as an add-on to treatment with long-acting bronchodilators. It may have a role as an alternative to inhaled corticosteroids in more symptomatic COPD patients with frequent exacerbations, although direct comparisons are currently lacking. Please cite this paper as: Ulrik CS and Calverley PMA. Roflumilast: clinical benefit in patients suffering from COPD. Clin Respir J 2010; 4: 197,201. [source] Negative Pressure Wound Therapy Used to Heal Complex Urinary Fistula Wounds Following Renal Transplantation into an Ileal ConduitAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010Sarah Heap Transplantation into an ileal conduit is an established option for patients with end-stage renal failure and a nonfunctioning urinary tract. Urinary fistulae are more common following these complex transplants. Urinary fistula in this scenario can cause substantial morbidity and even result in graft loss. The management options depend on the viability of the transplant ureter, the level of local sepsis and the overall condition of the patient. Urinary diversion with a nephrostomy and ureteric stents has been described in aiding the healing of urinary leaks in renal transplants into a functioning urinary tract. We describe the successful use of negative wound pressure therapy to eradicate the local sepsis and help the healing of a recurrent urinary fistula following kidney transplantation into an ileal conduit. To our knowledge these are the first such cases reported in the literature. [source] Successful Induction of Remission With Rituximab for Relapse of ANCA-Associated Vasculitis Post-Kidney Transplant: Report of Two CasesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007D. Geetha Kidney transplantation should be considered the treatment of choice for patients with end-stage renal disease due to antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). However, relapses of AAV have been reported to occur in 9,40% of cases following kidney transplantation and may adversely affect allograft outcome. These relapses are usually treated with cyclophosphamide (CYC) and glucocorticoids, but the repeated use of CYC carries a risk of substantial toxicity that may limit or prohibit its use in some patients. B lymphocytes have been implicated in the pathogenesis of AAV, and their depletion has been effective as salvage therapy for refractory disease in the nontransplant setting. We report the successful induction of remission using rituximab in two patients who suffered relapse of AAV post-kidney transplant. Given the substantial morbidity and adverse effects of CYC, rituximab appears to be a suitable alternative agent to treat relapses of AAV posttransplantation. [source] COST, DEMOGRAPHICS AND INJURY PROFILE OF ADULT PEDESTRIAN TRAUMA IN INNER SYDNEYANZ JOURNAL OF SURGERY, Issue 1-2 2006Timothy J. Small Background: Pedestrian accidents are associated with substantial morbidity, mortality and cost; however, there has been very little published work on this topic in Australasia over recent years. The objective of this study was to examine the demographics, injury profile, outcomes and cost of pedestrian versus motor vehicle accidents in a central city hospital in Sydney. Methods: Consecutive pedestrians injured by motor vehicles and admitted as inpatients during the years 2002,2004 were identified from our prospective trauma registry. A retrospective review included patient profiles (age, sex, time of injury and blood alcohol), injury pattern, cost, morbidity and mortality. Results: A total of 180 patients (64% men and 36% women) with a mean age of 46 and mean injury severity score of 14.1 were identified. Two peak injury periods were observed: one between 17.00 and 18.00 hours (P < 0.01) and the other between 20.00 and 22.00 hours (P < 0.01). Significantly more injuries occurred on Friday (P < 0.01) and during autumn months (P < 0.05). Musculoskeletal (34.3%), head (31.8%) and external (20.2%) injuries predominated. Forty-nine per cent of patients tested positive for consuming alcohol, with an average blood alcohol concentration (BAC) of 0.22%. Alcohol consumption was associated with a worse outcome in terms of hospital and intensive care unit stay, morbidity and mortality. The average length of stay was 13.4 days costing $A16320 per admission. Sixteen patients died (mortality rate of 8.9%), with the highest rate in the elderly group (22.7%) (P < 0.001). Conclusions: Pedestrian accidents in inner Sydney are common with injuries predominating in intoxicated adult males. Mortality was higher in the elderly group. Injuries to the head and lower extremities predominate. Hospital stays are lengthy, resulting in a high cost for each admission. [source] Dendritic cells in cytomegalovirus infection: viral evasion and host countermeasuresAPMIS, Issue 5-6 2009ALEXANDER RÖLLE Human cytomegalovirus (HCMV) is a ,-herpesvirus that infects the majority of the population during early childhood and thereafter establishes life-long latency. Primary infection as well as spontaneous reactivation usually remains asymptomatic in healthy hosts but can, in the context of systemic immunosuppression, result in substantial morbidity and mortality. HCMV counteracts the host immune response by interfering with the recognition of infected cells. A growing body of literature has also suggested that the virus evades the immune system by paralyzing the initiators of antiviral immune responses , the dendritic cells (DCs). In the current review, we discuss the effects of CMV (HCMV and murine CMV) on various DC subsets and the ensuing innate and adaptive immune responses. The impact of HCMV on DCs has mainly been investigated using monocyte-derived DCs, which are rendered functionally impaired by infection. In mouse models, DCs are targets of viral evasion as well, but the complex cross-talk between DCs and natural killer cells has, however, demonstrated an instrumental role for DCs in the control and clearance of viral infection. Fewer studies address the role of peripheral blood DC subsets, plasmacytoid DCs and CD11c+ myeloid DCs in the response against HCMV. These DCs, rather than being paralyzed by HCMV, are largely resistant to infection, mount a vigorous first-line defense and induce T-cell responses to the virus. This possibly provides a partial explanation for an intriguing conundrum: the highly efficient control of viral infection and reactivation in immunocompetent hosts in spite of multi-layered viral evasion mechanisms. [source] Transcription of proteinase 3 and related myelopoiesis genes in peripheral blood mononuclear cells of patients with active Wegener's granulomatosisARTHRITIS & RHEUMATISM, Issue 6 2010Chris Cheadle Objective Wegener's granulomatosis (WG) is a systemic inflammatory disease that is associated with substantial morbidity. The aim of this study was to understand the biology underlying WG and to discover markers of disease activity that would be useful for prognosis and treatment guidance. Methods Gene expression profiling was performed using total RNA from peripheral blood mononuclear cells (PBMCs) and granulocyte fractions from 41 patients with WG and 23 healthy control subjects. Gene set enrichment analysis (GSEA) was performed to search for candidate WG-associated molecular pathways and disease activity biomarkers. Principal components analysis was used to visualize relationships between subgroups of WG patients and controls. Longitudinal changes in proteinase 3 (PR3) gene expression were evaluated using reverse transcription,polymerase chain reaction, and clinical outcomes, including remission status and disease activity, were determined using the Birmingham Vasculitis Activity Score for WG (BVAS-WG). Results Eighty-six genes in WG PBMCs and 40 in WG polymorphonuclear neutrophils (PMNs) were significantly up-regulated relative to controls. Genes up-regulated in WG PBMCs were involved in myeloid differentiation, and these included the WG autoantigen PR3. The coordinated regulation of myeloid differentiation genes was confirmed by GSEA. The median expression values of the 86 up-regulated genes in WG PBMCs were associated with disease activity (P = 1.3 × 10,4), and WG patients with low-level expression of the WG signature genes showed expression profiles that were only modestly different from that in healthy controls (P = 0.07). PR3 transcription was significantly up-regulated in WG PBMCs (P = 1.3 × 10,5, false discovery rate [FDR] 0.002), but not in WG PMNs (P = 0.03, FDR 0.28), and a preliminary longitudinal analysis showed that the fold change in PR3 RNA levels in WG PBMCs corresponded to changes in the BVAS-WG score over time. Conclusion Transcription of PR3 and related myeloid differentiation genes in PBMCs may represent novel markers of disease activity in WG. [source] Bridge-to-recovery from Acute Myocarditis in a 12-year-old ChildARTIFICIAL ORGANS, Issue 6 2004Holger Hotz Abstract:, Fulminant myocarditis causes substantial morbidity and mortality, especially in children and young adults. Mechanical circulatory support has become the standard therapy to bridge patients with intractable heart failure to either transplantation or myocardial recovery. Yet, successful weaning from biventricular support with full recovery is extremely rare in the pediatric population. This report describes the successful use of the MEDOS HIA ventricular assist device to bridge a 12-year-old girl to myocardial recovery in a biventricular bypass configuration. The left and right ventricle were completely off-loaded by the pumps and the device provided sufficient cardiac output to normalize end-organ function. Anticoagulation was maintained with i.v. heparin infusion. No neurological complications were detectable and the pump system was free of any macroscopic thrombi. After 19 days of support, cardiac function had recovered and the patient was successfully weaned from the device. Following physical rehabilitation, the patient was discharged home. [source] An 11-year experience of enterocutaneous fistula,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 12 2004P. Hollington Background: Enterocutaneous fistula has traditionally been associated with substantial morbidity and mortality, related to fluid, electrolyte and metabolic disturbance, sepsis and malnutrition. Methods: A retrospective review of enterocutaneous fistula in 277 consecutive patients treated over an 11-year period in a major tertiary referral centre was undertaken to evaluate current management practice and outcome. Results: Most fistulas occurred secondary to abdominal surgery, and a high proportion (52·7 per cent) occurred in association with inflammatory bowel disease. A low rate of spontaneous healing was observed (19·9 per cent). The healing rate after definitive fistula surgery was 82·0 per cent, although more than one attempt was required to achieve surgical closure in some patients. Definitive fistula resection resulted in a mortality rate of 3·0 per cent. In addition, one patient died after laparotomy for intra-abdominal sepsis and an additional 24 patients died from complications of fistulation, giving an overall fistula-related mortality rate of 10·8 per cent. Conclusion: Early recognition and control of sepsis, management of fluid and electrolyte imbalances, meticulous wound care and nutritional support appear to reduce the mortality rate, and allow spontaneous fistula closure in some patients. Definitive surgical management is performed only after restitution of normal physiology, usually after at least 6 months. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Neoadjuvant chemoradiotherapy for operable oesophageal carcinoma: preliminary results from SheffieldBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2001I. McL. Background: Surgical resection is the mainstay of treatment for potentially curable oesophageal carcinoma but the long-term survival rate remains 10,20 per cent. Neoadjuvant administration of chemoradiotherapy (NCR) may improve these values. In this study the authors reviewed their preliminary experience with NCR in Sheffield. Methods: Twenty-five patients with potentially resectable oesophageal carcinoma embarked on a regimen of NCR, with resection planned 4,6 weeks later. Chemotherapy incorporated two cycles of intravenous cis -platinum and 5-fluorouracil with external-beam radiotherapy administered synchronously (30,45 Gy). Results: Twenty-two of the 25 patients suffered side-effects from NCR, including one death, and seven patients failed to complete NCR as planned. The median interval from diagnosis to surgery was 121 days. Twelve out of 24 patients had significant postoperative complications, including two deaths. Seven patients had a complete histological response to NCR (three out of 15 for adenocarcinoma, four out of nine for squamous carcinoma). Conclusion: The complete histological response rate to NCR in these patients compares favourably with previous studies, as does the postoperative mortality, but this was at the expense of substantial morbidity and was associated with long delays from diagnosis to operation. At present it is not possible to predict which patients will respond favourably to NCR and whether they will benefit with improved survival. © 2001 British Journal of Surgery Society Ltd [source] Analysis of 153 gunshot wounds of the liverBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2000J. D. F. Marr Background Gunshot wounds of the liver may result in substantial morbidity and death, and optimal management of complex injuries is controversial. Methods One hundred and fifty-three patients with civilian gunshot liver injuries were treated during the 10-year period 1986,1995. Demographic, clinical and operative data were recorded. Factors influencing postoperative complications and death were analysed. Results One hundred and forty-two patients (93 per cent) had single missile injuries and 11 (7 per cent) had shotgun injuries. Three patients were treated non-operatively and 150 patients underwent operation. In 105 patients (70 per cent) the injuries to the liver were minor and required either no treatment (93) or simple suture of bleeding vessels (12). Forty-five patients (30 per cent) had major injuries which were either packed only (26) or required more complex surgical intervention (19). This included resectional debridement (ten), major venous repair (eight) and hepatotomy (one); eight of these patients required packing combined with the procedure. Associated intra-abdominal injuries occurred in 115 patients (77 per cent). The overall mortality rate was 17 per cent (26 patients). Death was directly attributable to the liver injury in 13 patients (8 per cent), 12 of whom died from uncontrolled bleeding. Complications occurred in 63 (51 per cent) of 124 survivors, and correlated with the type and severity of the liver injury and the number of associated injuries. Conclusion Most gunshot liver injuries can be managed by simple surgical techniques. In complex injuries control of major haemorrhage is vital and perihepatic packing may be life saving before undertaking definitive repair of the injury under controlled conditions. © 2000 British Journal of Surgery Society Ltd [source] Children with Bacterial Meningitis Presenting to the Emergency Department during the Pneumococcal Conjugate Vaccine EraACADEMIC EMERGENCY MEDICINE, Issue 6 2008Lise E. Nigrovic MD Abstract Background:, The epidemiology of bacterial meningitis in children in the era of widespread heptavalent conjugate pneumococcal vaccination (PCV7) is unknown. Objectives:, The objective was to describe the epidemiology of bacterial meningitis in children presenting to the emergency department (ED) during the era of widespread PCV7 vaccination. Methods:, The authors retrospectively reviewed the medical records of all children aged 1 month to 19 years with bacterial meningitis who presented to the EDs of 20 U.S. pediatric centers (2001,2004). Bacterial meningitis was defined by a positive cerebrospinal fluid (CSF) culture for a bacterial pathogen or CSF pleocytosis (CSF white blood cell [WBC] count ,10 cells/mm3) in association with either a positive blood culture or a CSF latex agglutination study. Results:, A total of 231 children with bacterial meningitis were identified. The median age was 0.6 years (interquartile range [IQR] = 0.2,4.2). Eight patients (3% of all patients) died. The following bacterial pathogens were identified: Streptococcus pneumoniae (n = 77; 33.3%), Neisseria meningitidis (67; 29.0%), Group B Streptococcus (42; 18.2%), Escherichia coli (17; 7.4%), nontypeable Haemophilus influenzae (10; 4.3%), other Gram-negative bacilli (7; 3.0%), Listeria monocytogenes (5; 2.2%), Group A Streptococcus (5; 2.2%), and Moraxella catarrhalis (1; 0.4%). S. pneumoniae serotypes were determined in 37 of 77 patients; of these, 62% were due to nonvaccine serotypes (including 19A). Conclusions:, Although now a rare infectious disease in United States, bacterial meningitis still causes substantial morbidity in affected children. Despite the introduction of PCV7, S. pneumoniae remains the most common cause of bacterial meningitis in U.S. children, with approximately half of cases due to nonvaccine serotypes. [source] Glucagon-like Peptide-1 and Myocardial Protection: More than Glycemic ControlCLINICAL CARDIOLOGY, Issue 5 2009Anjali V. Fields MD Pharmacologic intervention for the failing heart has traditionally targeted neurohormonal activation and ventricular remodeling associated with cardiac dysfunction. Despite the multitude of agents available for the treatment of heart failure, it remains a highly prevalent clinical syndrome with substantial morbidity and mortality, necessitating alternative strategies of targeted management. One such area of interest is the ability to modulate myocardial glucose uptake and its impact on cardioprotection. Glucose-insulin-potassium (GIK) infusions have been studied for decades, with conflicting results regarding benefit in acute myocardial infarction. Based on the same concepts, glucagon-like peptide-1-[7,36] amide (GLP-1) has recently been demonstrated to be a more effective alternative in left ventricular (LV) systolic dysfunction. This paper provides a review on the current evidence supporting the use of GLP-1 in both animal models and humans with ischemic and nonischemic cardiomyopathy. Copyright © 2009 Wiley Periodicals, Inc. [source] | ||||||||||||||||||||||||||||