MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options.

PubMed

El-Hattab, Ayman W; Adesina, Adekunle M; Jones, Jeremy; Scaglia, Fernando

2015-01-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)). The m.3243A>G mutation results in impaired mitochondrial translation and protein synthesis including the mitochondrial electron transport chain complex subunits leading to impaired mitochondrial energy production. The inability of dysfunctional mitochondria to generate sufficient energy to meet the needs of various organs results in the multi-organ dysfunction observed in MELAS syndrome. Energy deficiency can also stimulate mitochondrial proliferation in the smooth muscle and endothelial cells of small blood vessels leading to angiopathy and impaired blood perfusion in the microvasculature of several organs. These events will contribute to the complications observed in MELAS syndrome particularly the stroke-like episodes. In addition, nitric oxide deficiency occurs in MELAS syndrome and can contribute to its complications. There is no specific consensus approach for treating MELAS syndrome. Management is largely symptomatic and should involve a multidisciplinary team. Unblinded studies showed that l-arginine therapy improves stroke-like episode symptoms and decreases the frequency and severity of these episodes. Additionally, carnitine and coenzyme Q10 are commonly used in MELAS syndrome without proven efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines.

PubMed

Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

2010-06-01

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi-organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome.

PubMed

Adachi, Naoto; Hirota, Masahiko; Hamaguchi, Masamichi; Okamoto, Kazufumi; Watanabe, Keisuke; Endo, Fumio

2004-04-01

Apoptosis may play an important role in the development of systemic inflammatory response syndrome (SIRS) and progression to multiple organ dysfunction syndrome (MODS). To quantify the extent of apoptosis in these morbidities, we developed a sandwich ELISA system to measure serum cytochrome c (cyt-c) levels and we investigated the prognostic significance of cyt-c concentration in SIRS/MODS patients. Cyt-c concentrations in patients with SIRS (n=53) with or at risk for MODS were measured and compared with those of control subjects (n=14). Cyt-c concentrations in SIRS/MODS patients increased (0.24-210 ng/ml), whereas those in control subjects were under detection limits (0.1 ng/ml). Cyt-c concentrations in non-survivors increased significantly compared with those in survivors both on the day of admission and on the fifth hospital day. A significant positive correlation was found between cyt-c concentration and two representative organ dysfunction scores, APACHE II and multi-organ failure (MOF) score. Cyt-c concentrations increased earlier than MOF score during the exacerbation phase and rapidly decreased during the convalescence phase in a survivor, but the level continued to be high in a non-survivor. Determination of serum cyt-c concentrations may be useful to assess the severity of organ dysfunction and to predict the prognosis of SIRS/MODS patients.

[Bardet-Biedl syndrome: cilia and obesity - from genes to integrative approaches].

PubMed

Chennen, Kirsley; Scerbo, Maria Julia; Dollfus, Hélène; Poch, Olivier; Marion, Vincent

2014-11-01

The primary cilium is a specialized organelle, present at the surface of most eukaryotic cells, whose main function is to detect, integrate and transmit intra- and extra-cellular signals. Its dysfunction usually results in a group of severe clinical manifestations nowadays termed ciliopathies. The latter can be of syndromic nature with multi-organ dysfunctions and can also be associated with a morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet Biedl syndrome (BBS). This review will discuss the contribution of the unique context offered by the emblematic BBS for understanding the mechanisms leading to obesity via the involvement of the primary cilium together with identification of novel molecular players and signaling pathways it has helped to highlight. In the current context of translational medicine and system biology, this article will also discuss the potential benefits and challenges posed by these techniques via multi-level approaches to better dissect the underlying mechanisms leading to the complex condition of obesity. © 2014 médecine/sciences – Inserm.

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

PubMed

Lin, John C; Spinella, Philip C; Fitzgerald, Julie C; Tucci, Marisa; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

2017-01-01

To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Secondary analysis of a prospective, cross-sectional, point prevalence study. International, multicenter PICUs. Pediatric patients with severe sepsis identified on five separate days over a 1-year period. None. Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

[Secondary amyloidosis in patients with rheumatoid arthritis(RA)].

PubMed

Inada, Shinichi

2002-12-01

The amyloidoses are a group of protein deposition diseases in which amyloid proteins composed of insoluble fibrils are deposited in various organs. Most cases of the secondary amyloidosis(AA amyloidosis) in which amyloid A(AA) protein is deposited followed by uncontrolled, long term RA(duration 7 to 10 years). It has been revealed that the multi-organ dysfunction associated with AA amyloidosis causes the deterioration of RA prognosis. Since the mechanism of amyloid protein deposition is still unknown, the diagnosis of AA amyloidosis is difficult and there is no fundamental therapy for it; there are only supportive therapies for the malfunction of involved organs.

Scrub typhus in South India: clinical and laboratory manifestations, genetic variability, and outcome.

PubMed

Varghese, George M; Janardhanan, Jeshina; Trowbridge, Paul; Peter, John V; Prakash, John A J; Sathyendra, Sowmya; Thomas, Kurien; David, Thambu S; Kavitha, M L; Abraham, Ooriapadickal C; Mathai, Dilip

2013-11-01

This study sought to document the clinical and laboratory manifestations, genetic variability, and outcomes of scrub typhus, an often severe infection caused by Orientia tsutsugamushi, in South India. Patients admitted to a large teaching hospital with IgM ELISA-confirmed scrub typhus were evaluated. Clinical examination with a thorough search for an eschar, laboratory testing, chest X-ray, and outcome were documented and analyzed. Additionally, a 410-bp region of the 56-kDa type-specific antigen gene of O. tsutsugamushi was sequenced and compared with isolates from other regions of Asia. Most of the 154 patients evaluated presented with fever and non-specific symptoms. An eschar was found in 86 (55%) patients. Mild hepatic involvement was seen in most, with other organ involvement including respiratory, cardiovascular, and renal. Multi-organ dysfunction was noted in 59 (38.3%), and the fatality rate was 7.8%. Hypotension requiring vasoactive agents was found to be an independent predictor of mortality (p<0.001). The phylogeny of 26 samples showed 17 (65%) clustering with the Kato-like group and eight (31%) with the Karp-like group. The presentation of scrub typhus can be variable, often non-specific, but with potentially severe multi-organ dysfunction. Prompt recognition is key to specific treatment and good outcomes. Further study of the circulating strains is essential for the development of a successful vaccine and sensitive point-of-care testing. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Systemic Inflammatory Response Syndrome, Quick Sequential Organ Function Assessment, and Organ Dysfunction: Insights From a Prospective Database of ED Patients With Infection.

PubMed

Williams, Julian M; Greenslade, Jaimi H; McKenzie, Juliet V; Chu, Kevin; Brown, Anthony F T; Lipman, Jeffrey

2017-03-01

A proposed revision of sepsis definitions has abandoned the systemic inflammatory response syndrome (SIRS), defined organ dysfunction as an increase in total Sequential Organ Function Assessment (SOFA) score of ≥ 2, and conceived "qSOFA" (quick SOFA) as a bedside indicator of organ dysfunction. We aimed to (1) determine the prognostic impact of SIRS, (2) compare the diagnostic accuracy of SIRS and qSOFA for organ dysfunction, and (3) compare standard (Sepsis-2) and revised (Sepsis-3) definitions for organ dysfunction in ED patients with infection. Consecutive ED patients admitted with presumed infection were prospectively enrolled over 3 years. Sufficient observational data were collected to calculate SIRS, qSOFA, SOFA, comorbidity, and mortality. We enrolled 8,871 patients, with SIRS present in 4,176 (47.1%). SIRS was associated with increased risk of organ dysfunction (relative risk [RR] 3.5) and mortality in patients without organ dysfunction (OR 3.2). SIRS and qSOFA showed similar discrimination for organ dysfunction (area under the receiver operating characteristic curve, 0.72 vs 0.73). qSOFA was specific but poorly sensitive for organ dysfunction (96.1% and 29.7%, respectively). Mortality for patients with organ dysfunction was similar for Sepsis-2 and Sepsis-3 (12.5% and 11.4%, respectively), although 29% of patients with Sepsis-3 organ dysfunction did not meet Sepsis-2 criteria. Increasing numbers of Sepsis-2 organ system dysfunctions were associated with greater mortality. SIRS was associated with organ dysfunction and mortality, and abandoning the concept appears premature. A qSOFA score ≥ 2 showed high specificity, but poor sensitivity may limit utility as a bedside screening method. Although mortality for organ dysfunction was comparable between Sepsis-2 and Sepsis-3, more prognostic and clinical information is conveyed using Sepsis-2 regarding number and type of organ dysfunctions. The SOFA score may require recalibration. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Fatal warm autoimmune hemolytic anemia in a child due to IgM-type autoantibodies.

PubMed

Takahashi, Hiroyuki; Tanaka, Fumiko; Sakuma, Hiroyuki; Sato, Mutsumi; Inaba, Shoichi; Kai, Sumio

2016-08-01

Herein is described a case of immunoglobulin M (IgM) warm autoimmune hemolytic anemia (AIHA) in a child who consequently died within 3 days of clinical onset. A previously healthy 11-year-old boy presented with fever, anemia, jaundice, and deteriorating consciousness. On direct agglutination test against group O red blood cells, agglutination was seen even at 37°C in saline, which was abolished on dithiothreitol treatment of the serum, indicating that the responsible autoantibody was IgM and had a warm-reactive capacity. A diagnosis of IgM warm AIHA was therefore made. Hemagglutination in the visceral capillaries was considered as the direct cause of organ dysfunction. The patient died due to respiratory failure. IgM warm AIHA is a very severe condition that is difficult to reverse in an advanced state. Both prompt, definite diagnosis and intervention are therefore vital to prevent severe multi-organ dysfunction in cases of IgM warm AIHA. © 2016 Japan Pediatric Society.

Effect of spinal anterior root stimulation and sacral deafferentation on bladder and sexual dysfunction in spinal cord injury.

PubMed

Zaer, Hamed; Rasmussen, Mikkel Mylius; Zepke, Franko; Bodin, Charlotte; Domurath, Burkhard; Kutzenberger, Johannes

2018-05-10

Spinal cord injury (SCI) is a highly devastating injury with a variety of complications; among them are neurogenic bladder, bowel, and sexual dysfunction. We aimed to evaluate the effect of sacral anterior root stimulation with sacral deafferentation (SARS-SDAF) on neurogenic bladder and sexual dysfunction in a large well-defined spinal cord injury cohort. In the manner of cross-sectional study, subjects undergone SARS-SDAF between September 1986 and July 2011 answered a questionnaire concerning conditions before and after surgery in the department of Neuro-Urology, Bad Wildungen, Germany. In total 287 of 587 subjects were analyzed. Median age was 49 years (range 19-80), median time from SCI to surgery was 10 years (range 0-49), and from surgery to follow-up 13 years (range 1-25). Of the analyzed subjects, 100% of both gender used SARS for bladder emptying. On the visual analogue scale (VAS) ranging from 0 to 10 (best), satisfaction with SARS-SDAF was 10 concerning bladder emptying, however 5 and 8 regarding sexual performance, for female and male users, respectively. Baseline and follow-up comparison showed a decline in self-intermittent catheterization (p < 0.0001), partial catheterization by attendant (p = 0.0125), complete catheterization and suprapubic catheterization (p < 0.0001), transurethral catheterization (p < 0.0011), and fewer cases of involuntary urine leakage (p < 0.0001). The SARS-SDAF is a beneficial multi-potential treatment method with simultaneous positive effect on multi-organ dysfunction among SCI subjects.

Parkinson's: a syndrome rather than a disease?

PubMed

Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray

2017-08-01

Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness.

PubMed

De Rosa, Silvia; Samoni, Sara; Villa, Gianluca; Ronco, Claudio

2017-01-01

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. © 2017 S. Karger AG, Basel.

Systems Biology and Biomechanical Model of Heart Failure

PubMed Central

Louridas, George E; Lourida, Katerina G

2012-01-01

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies. PMID:22935019

Task Dependent Prefrontal Dysfunction in Persons with Asperger's Disorder Investigated with Multi-Channel Near-Infrared Spectroscopy

ERIC Educational Resources Information Center

Iwanami, Akira; Okajima, Yuka; Ota, Haruhisa; Tani, Masayuki; Yamada, Takashi; Hashimoro, Ryuichiro; Kanai, Chieko; Watanabe, Hiromi; Yamasue, Hidenori; Kawakubo, Yuki; Kato, Nobumasa

2011-01-01

Dysfunction of the prefrontal cortex has been previously reported in individuals with Asperger's disorder. In the present study, we used multi-channel near-infrared spectroscopy (NIRS) to detect changes in the oxygenated hemoglobin concentration ([oxy-Hb]) during two verbal fluency tasks. The subjects were 20 individuals with Asperger's disorder…

Toxic Shock Syndrome: An Unusual Organism.

PubMed

Young, Katie; Luni, Faraz Khan; Yoon, Youngsook

2016-07-01

Streptococcal toxic shock syndrome is a rapidly fatal disease causing hypotension with multi organ dysfunction (MODS) early in the course of infection, which by definition is caused by Group A streptococcus (GAS). We describe a case of Toxic Shock like Syndrome (TSLS) in which the causative organism was not a GAS. A 71-year-old woman with hepatitis C and primary biliary cirrhosis had sudden onset of slurred speech and left arm and facial numbness. She had bilateral erythematous macular rash present on the flanks and legs. She was started on empiric antibiotics but her condition rapidly deteriorated 6 hours after admission. During this time, the development of multiple large reddish-pink areas of ecchymosis with bullae on her lower extremities, flanks, and groin were noted. She also developed multiorgan dysfunction (MODS) with renal dysfunction, coagulopathy and liver involvement. Patient expired before surgery could be performed and the time from presentation to the time of death was 16 hours. The blood and bullae fluid cultures grew Streptococcus dysgalactiae equisimilis. Streptococcus dysgalactiae equisimilis is a rare cause of TSLS which typically affects elderly or immunocompromised patients and only a few cases have been described in the literature. Our patient met criteria for TSLS which caused rapid shock and MODS. We review the literature of the cases describing the clinical characteristics of TSLS cause by non-GAS. Group G Streptococci is a rare but lethal cause of streptococcal toxic shock syndrome. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients

PubMed Central

Yang, Shuna; Li, Yue; Yuan, Junliang; Yang, Lei; Li, Shujuan; Hu, Wenli

2016-01-01

Background Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients. Methods Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated. Results 33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019–1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105–4.978) were independent risk factors for development of MODS. Conclusions In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality, suggesting that early identification of MODS is critical important. PMID:27893797

Number of organ dysfunctions predicts mortality in emergency department patients with suspected infection: a multicenter validation study.

PubMed

Jessen, Marie K; Skibsted, Simon; Shapiro, Nathan I

2017-06-01

The aim of this study was to validate the association between number of organ dysfunctions and mortality in emergency department (ED) patients with suspected infection. This study was conducted at two medical care center EDs. The internal validation set was a prospective cohort study conducted in Boston, USA. The external validation set was a retrospective case-control study conducted in Aarhus, Denmark. The study included adult patients (>18 years) with clinically suspected infection. Laboratory results and clinical data were used to assess organ dysfunctions. Inhospital mortality was the outcome measure. Multivariate logistic regression was used to determine the independent mortality odds for number and types of organ dysfunctions. We enrolled 4952 (internal) and 483 (external) patients. The mortality rate significantly increased with increasing number of organ dysfunctions: internal validation: 0 organ dysfunctions: 0.5% mortality, 1: 3.6%, 2: 9.5%, 3: 17%, and 4 or more: 37%; external validation: 2.2, 6.7, 17, 41, and 57% mortality (both P<0.001 for trend). Age-adjusted and comorbidity-adjusted number of organ dysfunctions remained an independent predictor. The effect of specific types of organ dysfunction on mortality was most pronounced for hematologic [odds ratio (OR) 3.3 (95% confidence interval (CI) 2.0-5.4)], metabolic [OR 3.3 (95% CI 2.4-4.6); internal validation], and cardiovascular dysfunctions [OR 14 (95% CI 3.7-50); external validation]. The number of organ dysfunctions predicts sepsis mortality.

Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis.

PubMed

Scott, Halden F; Brou, Lina; Deakyne, Sara J; Fairclough, Diane L; Kempe, Allison; Bajaj, Lalit

2016-03-01

To evaluate whether lactate clearance and normalization during emergency care of pediatric sepsis is associated with lower rates of persistent organ dysfunction. This was a prospective cohort study of 77 children <18 years of age in the emergency department with infection and acute organ dysfunction per consensus definitions. In consented patients, lactate was measured 2 and/or 4 hours after an initial lactate; persistent organ dysfunction was assessed through laboratory and physician evaluation at 48 hours. A decrease of ≥ 10% from initial to final level was considered lactate clearance; a final level < 2 mmol/L was considered lactate normalization. Relative risk (RR) with 95% CIs, adjusted in a log-binomial model, was used to evaluate associations between lactate clearance/normalization and organ dysfunction. Lactate normalized in 62 (81%) patients and cleared in 70 (91%). The primary outcome, persistent 48-hour organ dysfunction, was present in 32 (42%). Lactate normalization was associated with decreased risk of persistent organ dysfunction (RR 0.46, 0.29-0.73; adjusted RR 0.47, 0.29-0.78); lactate clearance was not (RR 0.70, 0.35-1.41; adjusted RR 0.75, 0.38-1.50). The association between lactate normalization and decreased risk of persistent organ dysfunction was retained in the subgroups with initial lactate ≥ 2 mmol/L and hypotension. In children with sepsis and organ dysfunction, lactate normalization within 4 hours was associated with decreased persistent organ dysfunction. Serial lactate level measurement may provide a useful prognostic tool during the first hours of resuscitation in pediatric sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Specific Etiologies Associated With the Multiple Organ Dysfunction Syndrome in Children: Part 2.

PubMed

Upperman, Jeffrey S; Bucuvalas, John C; Williams, Felicia N; Cairns, Bruce A; Cox, Charles S; Doctor, Allan; Tamburro, Robert F

2017-03-01

To describe a number of conditions and therapies associated with multiple organ dysfunction syndrome presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Multiple Organ Dysfunction Workshop (March 26-27, 2015). In addition, the relationship between burn injuries and multiple organ dysfunction syndrome is also included although it was not discussed at the workshop. Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions and therapies were presented, discussed, and debated with a focus on identifying knowledge gaps and the research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Sepsis and trauma are the two conditions most commonly associated with multiple organ dysfunction syndrome both in children and adults. However, many other pathophysiologic processes may result in multiple organ dysfunction syndrome. In this article, we discuss conditions such as liver failure and pancreatitis, pathophysiologic processes such as ischemia and hypoxia, and injuries such as trauma and burns. Additionally, therapeutic interventions such as medications, blood transfusions, transplantation may also precipitate and contribute to multiple organ dysfunction syndrome. The purpose of this article is to describe the association of multiple organ dysfunction syndrome with a variety of conditions and therapies in an attempt to identify similarities, differences, and opportunities for therapeutic intervention.

Diaphragm Dysfunction in Mechanically Ventilated Patients.

PubMed

Dot, Irene; Pérez-Teran, Purificación; Samper, Manuel-Andrés; Masclans, Joan-Ramon

2017-03-01

Muscle involvement is found in most critical patients admitted to the intensive care unit (ICU). Diaphragmatic muscle alteration, initially included in this category, has been differentiated in recent years, and a specific type of muscular dysfunction has been shown to occur in patients undergoing mechanical ventilation. We found this muscle dysfunction to appear in this subgroup of patients shortly after the start of mechanical ventilation, observing it to be mainly associated with certain control modes, and also with sepsis and/or multi-organ failure. Although the specific etiology of process is unknown, the muscle presents oxidative stress and mitochondrial changes. These cause changes in protein turnover, resulting in atrophy and impaired contractility, and leading to impaired functionality. The term 'ventilator-induced diaphragm dysfunction' was first coined by Vassilakopoulos et al. in 2004, and this phenomenon, along with injury cause by over-distention of the lung and barotrauma, represents a challenge in the daily life of ventilated patients. Diaphragmatic dysfunction affects prognosis by delaying extubation, prolonging hospital stay, and impairing the quality of life of these patients in the years following hospital discharge. Ultrasound, a non-invasive technique that is readily available in most ICUs, could be used to diagnose this condition promptly, thus preventing delays in starting rehabilitation and positively influencing prognosis in these patients. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical characteristics of children with group A streptococcal toxic shock syndrome admitted to pediatric intensive care units.

PubMed

Rodríguez-Nuñez, Antonio; Dosil-Gallardo, Silvia; Jordan, Iolanda

2011-05-01

Streptococcal toxic shock syndrome (STSS) is a very rare and severe form of group A streptococcal infection whose clinical characteristics, therapy, morbidity, and mortality in children are not well known. Our objective was to describe the clinical characteristics of STSS in a series of children admitted to pediatric intensive care units (PICU). A multicenter, retrospective study of children with STSS admitted to 14 PICUs between January 1998 and December 2009 was conducted. Clinical information was obtained retrospectively by chart review. Data from 41 children were collected, 90% corresponding to the second half of the study period. Initial symptoms and signs were nonspecific. All patients developed shock and organ dysfunction, 78.0% developed coagulopathy, 70.7% neurologic dysfunction, and 68.3% respiratory failure. Rapid pharyngeal test for Streptococcus was positive in 78.0%. Initial leukocyte count was quite variable, with leukopenia present in 51.2% of patients and leukocytosis in 31.7%. Children were treated with antibiotics against group A Streptococcus (GAS), usually G penicillin or cephalosporin plus clindamycin. After a median PICU stay of 7 days (range 0-41), 65.8% of patients survived, 26.8% with sequelae. The cause of death of the 11 non-survivors was refractory shock and multi-organ failure. STSS is a very severe condition secondary to invasive GAS infection. It can occur at any age, but especially in young children. Due to the lack of specific symptoms and signs and its very rapid progression to shock and organ dysfunction, pediatricians and emergency physicians must be aware of this possibility and immediately initiate aggressive treatment when suspected.

Venlafaxine intoxication with development of takotsubo cardiomyopathy: successful use of extracorporeal life support, intravenous lipid emulsion and CytoSorb®.

PubMed

Schroeder, Ines; Zoller, Michael; Angstwurm, Matthias; Kur, Felix; Frey, Lorenz

2017-07-05

We describe a young patient who ingested 18 g (240 times the daily therapeutic dose) of venlafaxine in a suicide attempt. She developed severe cardiomyopathy in a takotsubo distribution causing cardiogenic shock and multi-organ dysfunction syndrome (MODS). She was successfully treated with intravenous lipid emulsion (ILE), extracorporeal life support (ECLS) and CytoSorb®. This is remarkable as, to the best of the authors' knowledge, this is the highest amount of venlafaxine intake seen in the literature with a nonfatal outcome.

A hemicyanine based ratiometric fluorescence probe for mapping lysosomal pH during heat stroke in living cells.

PubMed

Wu, Luling; Wang, Yang; James, Tony D; Jia, Nengqin; Huang, Chusen

2018-05-29

Heat stroke is a lethal condition which can cause dysfunction in the central nervous system, multi-organ damage and even death. However, there is still limited knowledge of the detailed mechanism about the roles of lysosomes in heat stroke due to lack of effective tools. Herein, we introduce our previously developed hemicyanine with a large D-π-A structure as the key fluorophore to develop a new fluorescent probe (CPY) for ratiometric mapping of lysosomal pH changes in live cells under a heat shock stimulus.

Understanding the Full Spectrum of Organ Injury Following Intrapartum Asphyxia

PubMed Central

LaRosa, Domenic A.; Ellery, Stacey J.; Walker, David W.; Dickinson, Hayley

2017-01-01

Birth asphyxia is a significant global health problem, responsible for ~1.2 million neonatal deaths each year worldwide. Those who survive often suffer from a range of health issues including brain damage—manifesting as cerebral palsy (CP)—respiratory insufficiency, cardiovascular collapse, and renal dysfunction, to name a few. Although the majority of research is directed toward reducing the brain injury that results from intrapartum birth asphyxia, the multi-organ injury observed in surviving neonates is of equal importance. Despite the advent of hypothermia therapy for the treatment of hypoxic–ischemic encephalopathy (HIE), treatment options following asphyxia at birth remain limited, particularly in low-resource settings where the incidence of birth asphyxia is highest. Furthermore, although cooling of the neonate results in improved neurological outcomes for a small proportion of treated infants, it does not provide any benefit to the other organ systems affected by asphyxia at birth. The aim of this review is to summarize the current knowledge of the multi-organ effects of intrapartum asphyxia, with particular reference to the findings from our laboratory using the precocial spiny mouse to model birth asphyxia. Furthermore, we reviewed the current treatments available for neonates who have undergone intrapartum asphyxia, and highlight the emergence of maternal dietary creatine supplementation as a preventative therapy, which has been shown to provide multi-organ protection from birth asphyxia-induced injury in our preclinical studies. This cheap and effective nutritional supplement may be the key to reducing birth asphyxia-induced death and disability, particularly in low-resource settings where current treatments are unavailable. PMID:28261573

Prevalence of multiple organ dysfunction in the pediatric intensive care unit: Pediatric Risk of Mortality III versus Pediatric Logistic Organ Dysfunction scores for mortality prediction

PubMed Central

Hamshary, Azza Abd Elkader El; Sherbini, Seham Awad El; Elgebaly, HebatAllah Fadel; Amin, Samah Abdelkrim

2017-01-01

Objectives To assess the frequency of primary multiple organ failure and the role of sepsis as a causative agent in critically ill pediatric patients; and calculate and evaluate the accuracy of the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores to predict the outcomes of critically ill children. Methods Retrospective study, which evaluated data from patients admitted from January to December 2011 in the pediatric intensive care unit of the Children's Hospital of the University of Cairo. Results Out of 237 patients in the study, 72% had multiple organ dysfunctions, and 45% had sepsis with multiple organ dysfunctions. The mortality rate in patients with multiple organ dysfunction was 73%. Independent risk factors for death were mechanical ventilation and neurological failure [OR: 36 and 3.3, respectively]. The PRISM III score was more accurate than the PELOD score in predicting death, with a Hosmer-Lemeshow X2 (Chi-square value) of 7.3 (df = 8, p = 0.5). The area under the curve was 0.723 for PRISM III and 0.78 for PELOD. Conclusion A multiple organ dysfunctions was associated with high mortality. Sepsis was the major cause. Pneumonia, diarrhea and central nervous system infections were the major causes of sepsis. PRISM III had a better calibration than the PELOD for prognosis of the patients, despite the high frequency of the multiple organ dysfunction syndrome. PMID:28977260

The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock.

PubMed

Freitas, Flávio G R; Salomão, Reinaldo; Tereran, Nathalia; Mazza, Bruno Franco; Assunção, Murillo; Jackiu, Mirian; Fernandes, Haggeas; Machado, Flávia Ribeiro

2008-08-01

This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock. Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p<0.05. Fifty-six patients were enrolled. Mean age was 55.6+/-20.7 years, mean APACHE II score was 20.6+/-6.9, and mean SOFA score was 7.9+/-3.7. Thirty-six patients (64.3%) had septic shock. The mean duration of organ dysfunction was 1.9+/-1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008), onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05) and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001). These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock.

Alcoholism: A Multi-Systemic Cellular Insult to Organs.

PubMed

Dguzeh, Ucee; Haddad, Natasha C; Smith, Kathia T S; Johnson, John O; Doye, Angelia A; Gwathmey, Judith K; Haddad, Georges E

2018-05-28

Alcohol abuse can affect more than the heart and the liver. Many observers often do not appreciate the complex and differing aspects of alcohol's effects in pathophysiologies that have been reported in multiple organs. Chronic alcohol abuse is known to be associated with pathophysiological changes that often result in life-threatening clinical outcomes, e.g., breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, cardiomyopathy, and can be as far-reaching as to cause central nervous system disorders. In this review article, we will discuss the various organs impacted by alcohol abuse. The lack of clear guidelines on the amount and frequency of alcohol intake, complicated by personal demographics, make extrapolations to real-life practices at best difficult for public health policy-makers.

The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

PubMed

Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

2017-09-01

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies were limited. A pattern of persistent, rather than worsening, organ dysfunction preceded most deaths.

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

PubMed

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

A fatal case of streptococcal toxic shock syndrome caused by Streptococcus suis carrying tet (40) and tet (O/W/32/O), Italy.

PubMed

Mancini, Fabiola; Adamo, Francesco; Creti, Roberta; Monaco, Monica; Alfarone, Giovanna; Pantosti, Annalisa; Ciervo, Alessandra

2016-11-01

We report the first human fatal case of streptococcal toxic shock syndrome (STSS) caused by Streptococcus suis serotype 2 carrying the tetracycline efflux tet (40) gene and the tetracycline ribosomal protection tet (O/W/32/O) gene. The patient was splenectomized. The case was characterized by multi-organ dysfunction and disseminated intravascular coagulopathy, in accordance with the clinical parameters of STSS. More investigations are needed to improve the epidemiology and the pathogenesis of S. suis in human infection. Published by Elsevier Ltd.

Identifying increased risk of post-infarct people with diabetes using multi-lag Tone-Entropy analysis.

PubMed

Karmakar, Chandan; Jelinek, Herbert; Khandoker, Ahsan; Tulppo, Mikko; Makikallio, Timo; Kiviniemi, Antti; Huikuri, Heikki; Palaniswami, Marimuthu

2012-01-01

Diabetes mellitus is associated with multi-organ system dysfunction. One of the key causative factors is the increased blood sugar level that leads to an increase in free radical activity and organ damage including the cardiovascular and nervous system. Heart rhythm is extrinsically modulated by the autonomic nervous system and cardiac autonomic neuropathy or dysautonomia has been shown to lead to sudden cardiac death in people with diabetes due to the decrease in heart rate variability (HRV). Current algorithms for determining HRV describe only beat-to-beat variation and therefore do not consider the ability of a heart beat to influence a train of succeeding beats. Therefore mortality risk analysis based on HRV has often not been able to discern the presence of an increased risk. This study used a novel innovation of the tone-entropy algorithm by incorporating increased lag intervals and found that both the sympatho-vagal balance and total activity changed at larger lag intervals. Tone-Entropy was found to be better risk identifier of cardiac mortality in people with diabetes at lags higher than one and best at lag seven.

Dysfunction of mechanical heart valve prosthesis: experience with surgical management in 48 patients

PubMed Central

Ma, Wei-Guo; Hou, Bin; Abdurusul, Adiljan; Gong, Ding-Xu; Tang, Yue; Chang, Qian; Xu, Jian-Ping

2015-01-01

Background Dysfunction of mechanical heart valve prostheses is an unusual but potentially lethal complication after mechanical prosthetic valve replacement. We seek to report our experience with mechanical valve dysfunction regarding etiology, surgical techniques and early outcomes. Methods Clinical data of 48 patients with mechanical valve dysfunction surgically treated between October 1996 and June 2011 were analyzed. Results Mean age was 43.7±10.9 years and 34 were female (70.8%). The median interval from primary valve implantation to dysfunction was 44.5 months (range, 1 hour to 20 years). There were 21 emergent and 27 elective reoperations. The etiology was thrombosis in 19 cases (39.6%), pannus in 12 (25%), thrombosis and pannus in 11 (22.9%), improper disc orientation in 2 (4.1%), missing leaflet in 1 (2.1%), excessively long knot end in 1 (2.1%), endogenous factor in 1 (2.1%) and unidentified in 1 (2.1%). Surgical procedure was mechanical valve replacement in 37 cases (77.1%), bioprosthetic valve replacement in 7 (14.9%), disc rotation in 2 (4.2%) and excision of excessive knot end in 1 (2.1%). Early deaths occurred in 7 patients (14.6%), due to low cardiac output in 3 (6.3%), multi-organ failure in 2 (4.2%) and refractory ventricular fibrillation in 2 (4.2%). Complications occurred in 10 patients (20.8%). Conclusions Surgical management of mechanical valve dysfunction is associated with significant mortality and morbidity. Earlier identification and prompt reoperation are vital to achieving better clinical outcomes. The high incidence of thrombosis in this series highlights the need for adequate anticoagulation and regular follow-up after mechanical valve replacement. PMID:26793354

Validating the WHO Maternal Near Miss Tool in a high-income country.

PubMed

Witteveen, Tom; de Koning, Ilona; Bezstarosti, Hans; van den Akker, Thomas; van Roosmalen, Jos; Bloemenkamp, Kitty W

2016-01-01

This study was performed to assess the applicability of the WHO Maternal Near Miss Tool (MNM Tool) and the organ dysfunction criteria in a high-income country. The MNM tool was applied to 2552 women who died of pregnancy-related causes or sustained severe acute maternal morbidity between August 2004 and August 2006 in one of the 98 hospitals with a maternity unit in the Netherlands. Fourteen (0.6%) cases had insufficient data for application. Each case was assessed according to the three main "MNM categories" specified in the MNM tool and their subcategory criteria: five disease-, four intervention- and seven organ dysfunction-based criteria. Potentially life-threatening conditions (disease-based inclusions) and life-threatening cases (organ dysfunction-based inclusions) were differentiated according to WHO methodology. Outcomes were incidence of all (sub)categories and case-fatality rates. Of the 2538 cases, 2308 (90.9%) women fulfilled disease-based, 2116 (83.4%) intervention-based and 1024 (40.3%) organ dysfunction-based criteria. Maternal death occurred in 48 women, of whom 23 (47.9%) fulfilled disease-based, 33 (68.8%) intervention-based and 31 (64.6%) organ dysfunction-based criteria. Case-fatality rates were 23/2308 (1.0%) for cases fulfilling the disease-based criteria, 33/2116 (1.6%) for intervention-based criteria and 31/1024 (3.0%) for women fulfilling the organ dysfunction-based criteria. In the Netherlands, where advanced laboratory and clinical monitoring are available, organ dysfunction-based criteria of the MNM tool failed to identify nearly two-thirds of sustained severe acute maternal morbidity cases and more than one-third of maternal deaths. Disease-based criteria remain important, and using only organ dysfunction-based criteria would lead to underestimating severe acute maternal morbidity. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Acute hypopituitarism complicating Russell's viper envenomation: case series and systematic review.

PubMed

Rajagopala, S; Thabah, M M; Ariga, K K; Gopalakrishnan, M

2015-09-01

Chronic hypopituitarism following Russell viper envenomation (RVE) is a rare but well-recognized syndrome. The clinical features, associations, management and outcomes of RVE associated-acute hypopituitarism (AHP) are not well described. To describe the clinical features, intensive care unit (ICU) management and outcomes of a series of patients with RVE-AHP and identify the clinical associations of RVE-AHP. We describe a series of patients with prospectively identified AHP related to RVE and describe our findings comparing RVE with and without AHP and a systematic search of literature on AHP related to RVE. We identified nine cases of AHP related to RVE. Unexplained hypoglycemia (100%) and hypotension (66.7%) were the most common findings at presentation. AHP occurred after a median of 9 (range, 2-14) days after severe envenomation and was associated with multi-organ dysfunction, lower platelet counts, more bleeding and transfusions when compared to patients with RVE alone. The presence of clinically defined capillary leak syndrome, disseminated intravascular coagulation and mortality were not different from those without AHP. Our systematic search yielded 12 cases of AHP related to RVE; data on associated clinical manifestations, therapy and ASV administration were not available in most reports. AHP is a very rare complication of RVE. Unexplained hypoglycemia and hypotension should prompt evaluation for AHP in RVE. AHP is associated with severe RVE, multi-organ dysfunction, bleeding and need for transfusion. Prompt treatment with steroids may reduce mortality related to AHP in RVE. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina.

PubMed

Zhou, Hong-Tao; Yi, Hai-Su; Guo, Yong-Hui; Pan, Yu-Xian; Tao, Shao-Hua; Wang, Bin; Chen, Man-Jun; Yang, Mei; Yu, Nan

2016-03-16

A series of complications caused by enteroviruses, including meningitis, encephalitis, acute flaccid paralysis, acute cardiopulmonary failure, respiratory infection, and myocardial injury have been reported in hand, foot and mouth disease/herpangina (HFMD/HA). However, the complication of diarrhoea caused by enteroviruses has been neglected, and a summary of its clinical features and impact on HFMD/HA is unavailable. We included inpatients with HFMD/HA admitted to the Paediatric Department of Zhujiang Hospital during 2009-2012. We summarised and compared clinical data for cases with and without diarrhoea, and determined enterovirus serotypes by reverse transcriptase polymerase chain reaction and genotyping based on a partial-length fragment of viral protein 1 or the 5'-untranslated region. There were 804 inpatients with HFMD/HA and 28 (3.5%) presented with diarrhoea. Gastrointestinal symptoms were mild in most cases of diarrhoea (82.1%), with high prevalence of no dehydration (82.1%), short duration of diarrhoea (78.6%) and watery stools (75.0%). The prevalence of multi-organ dysfunction syndrome (10.7 vs 0.40%) (p = 0.001), hepatic injury (14.3 vs 3.4%) (p = 0.019), myocardial injury (21.4 vs 6.1%) (p = 0.002) and convulsion (21.4 vs 7.2%) (p = 0.016) was significantly higher in the diarrhoea than no diarrhoea group. There was no significant difference between the two groups regarding prevalence of death, altered consciousness, paralysis, central nervous system involvement, or acute respiratory infection. Most patients with diarrhoea caused by enteroviruses circulating in Guangdong Province in 2009-2012 had mild or moderate gastrointestinal symptoms. Although enterovirus-related diarrhoea caused additional multi-organ dysfunction syndrome, hepatic injury and myocardial injury in children with HFMD/HA, timely intervention efficiently reduced disease severity and improved outcome.

Mental health screening in women with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula in western Uganda.

PubMed

Krause, Hannah G; Hall, Barbara A; Ng, Shu-Kay; Natukunda, Harriet; Singasi, Isaac; Goh, Judith T W

2017-06-01

High levels of mental health dysfunction have been identified in women with genital tract fistula. The aim of this study was to use the General Health Questionnaire-28 (GHQ-28) to screen women in western Uganda with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula for risk of mental health dysfunction. Women undergoing surgery for severe pelvic organ prolapse, chronic fourth-degree obstetric tear, and genital tract fistula were interviewed using the GHQ-28 to screen for the risk of mental health dysfunction. A total of 125 women completed the GHQ-28, including 22 with pelvic organ prolapse, 47 with fourth-degree obstetric tear, 21 with genital tract fistula, and 35 controls. Nearly all women with these serious gynaecological conditions were positive for the risk of mental health dysfunction. In the domain assessing symptoms of severe depression, women with fourth-degree obstetric tear and genital tract fistula scored higher than women with pelvic organ prolapse. A significant risk of mental health dysfunction was identified in women with severe pelvic organ prolapse and chronic fourth-degree obstetric tear. These rates are similar to the high rates of mental health dysfunction in women with genital tract fistula. Identification and management of mental health dysfunction in women with these conditions should be a priority.

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion.

PubMed

Mai, Nguyen; Prifti, Landa; Rininger, Aric; Bazarian, Hannah; Halterman, Marc W

2017-11-01

Post-ischemic neurodegeneration remains the principal cause of mortality following cardiac resuscitation. Recent studies have implicated gastrointestinal ischemia in the sepsis-like response associated with the post-cardiac arrest syndrome (PCAS). However, the extent to which the resulting low-grade endotoxemia present in up to 86% of resuscitated patients affects cerebral ischemia-reperfusion injury has not been investigated. Here we report that a single injection of low-dose lipopolysaccharide (50μg/kg, IP) delivered after global cerebral ischemia (GCI) induces blood-brain barrier permeability, microglial activation, cortical injury, and functional decline in vivo, compared to ischemia alone. And while GCI was sufficient to induce neutrophil (PMN) activation and recruitment to the post-ischemic CNS, minimal endotoxemia exhibited synergistic effects on markers of systemic inflammation including PMN priming, lung damage, and PMN burden within the lung and other non-ischemic organs including the kidney and liver. Our findings predict that acute interventions geared towards blocking the effects of serologically occult endotoxemia in survivors of cardiac arrest will limit delayed neurodegeneration, multi-organ dysfunction and potentially other features of PCAS. This work also introduces lung-brain coupling as a novel therapeutic target with broad effects on innate immune priming and post-ischemic neurodegeneration following cardiac arrest and related cerebrovascular conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Adipose Tissue in Metabolic Syndrome: Onset and Progression of Atherosclerosis.

PubMed

Luna-Luna, María; Medina-Urrutia, Aida; Vargas-Alarcón, Gilberto; Coss-Rovirosa, Fernanda; Vargas-Barrón, Jesús; Pérez-Méndez, Óscar

2015-07-01

Metabolic syndrome (MetS) should be considered a clinical entity when its different symptoms share a common etiology: obesity/insulin resistance as a result of a multi-organ dysfunction. The main interest in treating MetS as a clinical entity is that the addition of its components drastically increases the risk of atherosclerosis. In MetS, the adipose tissue plays a central role along with an unbalanced gut microbiome, which has become relevant in recent years. Once visceral adipose tissue (VAT) increases, dyslipidemia and endothelial dysfunction follow as additive risk factors. However, when the nonalcoholic fatty liver is present, risk of a cardiovascular event is highly augmented. Epicardial adipose tissue (EAT) seems to increase simultaneously with the VAT. In this context, the former may play a more important role in the development of the atherosclerotic plaque than the latter. Hence, EAT may act as a paracrine tissue vis-à-vis the coronary arteries favoring the local inflammation and the atheroma calcification. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical Criteria for Sepsis in Children?

PubMed

Leclerc, Francis; Duhamel, Alain; Deken, Valérie; Grandbastien, Bruno; Leteurtre, Stéphane

2017-08-01

A recent task force has proposed the use of Sequential Organ Failure Assessment in clinical criteria for sepsis in adults. We sought to evaluate the predictive validity for PICU mortality of the Pediatric Logistic Organ Dysfunction-2 and of the "quick" Pediatric Logistic Organ Dysfunction-2 scores on day 1 in children with suspected infection. Secondary analysis of the database used for the development and validation of the Pediatric Logistic Organ Dysfunction-2. Nine university-affiliated PICUs in Europe. Only children with hypotension-low systolic blood pressure or low mean blood pressure using age-adapted cutoffs-and lactatemia greater than 2 mmol/L were considered in shock. We developed the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia, hypotension, and altered mentation (Glasgow < 11): one point for each variable (range, 0-3). Outcome was mortality at PICU discharge. Discrimination (Area under receiver operating characteristic curve-95% CI) and calibration (goodness of fit test) of the scores were studied. This study included 862 children with suspected infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86-0.96) in children with suspected infection, 0.88 (0.79-0.96) in those with low systolic blood pressure and hyperlactatemia, and 0.91 (0.85-0.97) in those with low mean blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49, respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater than or equal to 8 reflected an overall risk of mortality greater than or equal to 9.3% in children with suspected infection. Area under the curve of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76-0.87) with systolic blood pressure or mean blood pressure; calibration p value was 0.89 and 0.72, respectively. A score greater than or equal to 2 reflected a mortality risk greater than or equal to 19.8% with systolic blood pressure and greater than or equal to 15.9% with mean blood pressure. Among children admitted to PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on day 1 was highly predictive of PICU mortality suggesting its use to standardize definitions and diagnostic criteria of pediatric sepsis. Further studies are needed to determine the usefulness of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 outside of the PICU.

Biopsychosocial Management of Female Sexual Dysfunction: A Pilot Study of Patient Perceptions From 2 Multi-Disciplinary Clinics.

PubMed

Rullo, Jordan; Faubion, Stephanie S; Hartzell, Rose; Goldstein, Sue; Cohen, Deborah; Frohmader, Karla; Winter, Ashley G; Mara, Kristin; Schroeder, Darrell; Goldstein, Irwin

2018-05-19

Sexual dysfunction is often complex and biopsychosocial. Traditional sexual health care management involves individual providers not in a multi-disciplinary setting. A multi-disciplinary team may consist of a medical provider, pelvic floor physical therapist, and sex therapist. The aim was to explore the patient perceptions of benefit from management of their sexual dysfunction by a biopsychosocial multi-disciplinary team. A survey was e-mailed to women patients seen by multi-disciplinary teams at 2 different settings: San Diego Sexual Medicine or Mayo Clinic Women's Health Clinic during a 27-month period. Data are reported using summary statistics for age and count for remaining survey responses. Cochran-Armitage tests for trend were used to compare pre- and post-comfort levels. Main outcome measures included perceived benefit of being managed in a team-based model of care, level of benefit and satisfaction from each provider, and difference from pre-conceived level of comfort to actual comfort after each provider visit. 89 of 270 e-mailed surveys were analyzed. Patient populations (mean age 47.6, range 23-77 years) were similar between sites. Overall, 82% of respondents reported moderate/great benefit from the team-based model; 72.1% reported management by all 3 providers valuable/extremely valuable; and 84.3% were somewhat/very satisfied with the model. Women endorsed specific ways in which they benefitted from the team-based model including: improved sexual function (58.1%), feeling validated (72.1%) and listened to (62.8%), that they better understood their health concerns (65.1%), that their partner better understood their health concerns (46.5%), and feeling normal (46.5%). There were no significant differences between the 2 clinics in terms of patient-perceived benefit, value, or satisfaction. The team-based model of care for management of sexual dysfunction in women including a medical provider, physical therapist, and sex therapist is associated with patient-perceived benefit, satisfaction, and value. Rullo J, Faubion S, Hartzell R, et al. Biopsychosocial Management of Female Sexual Dysfunction: A Pilot Study of Patient Perceptions From 2 Multi-Disciplinary Clinics. Sex Med 2018;XX:XXX-XXX. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department

PubMed Central

Arnold, Ryan; Boyd, John H.; Zindovic, Marko; Zindovic, Igor; Lange, Anna; Paulsson, Magnus; Nyberg, Patrik; Russell, James A.; Pritchard, David; Christensson, Bertil; Åkesson, Per

2015-01-01

Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12–24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (> 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours. PMID:26468696

New therapy, new challenges: The effects of long-term continuous flow left ventricular assist device on inflammation.

PubMed

Grosman-Rimon, Liza; Billia, Filio; Fuks, Avi; Jacobs, Ira; A McDonald, Michael; Cherney, David Z; Rao, Vivek

2016-07-15

Surgically implanted continuous flow left ventricular assist devices (CF-LVADs) are currently used in patients with end-stage heart failure (HF). However, CF-LVAD therapy introduces a new set of complications and adverse events in these patients. Major adverse events with the CF-LVAD include right heart failure, vascular dysfunction, stroke, hepatic failure, and multi-organ failure, complications that may have inflammation as a common etiology. Our aim was to review the current evidence showing a relationship between these adverse events and elevated levels of inflammatory biomarkers in CF-LVAD recipients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tricuspid valve excision using off-pump inflow occlusion technique: role of intra-operative trans-esophageal echocardiography.

PubMed

Gadhinglajkar, Shrinivas; Sreedhar, Rupa; Karunakaran, Jayakumar; Misra, Manoranjan; Somasundaram, Ganesh; Mathew, Thomas

2010-01-01

A pacing system infection may lead to infective endocarditis and systemic sepsis. Tricuspid valve surgery may be required if the valve is severely damaged in the process of endocarditis. Although, cardiopulmonary bypass is the safe choice for performing right-heart procedures, it may carry risk of inducing systemic inflammatory response and multi-organ dysfunction. Some studies have advocated TV surgery without institution of CPB. We report tricuspid valve excision using the off-pump inflow occlusion technique in a 68-year-old man. We also describe role of intra-operative TEE as a monitoring tool at different stages of the surgical procedure.

Analysing UK clinicians' understanding of cognitive symptoms in major depression: A survey of primary care physicians and psychiatrists.

PubMed

McAllister-Williams, R Hamish; Bones, Kate; Goodwin, Guy M; Harrison, John; Katona, Cornelius; Rasmussen, Jill; Strong, Sarah; Young, Allan H

2017-01-01

Cognitive dysfunction occurs in depression and can persist into remission. It impacts on patient functioning but remains largely unrecognised, unmonitored and untreated. We explored understanding of cognitive dysfunction in depression among UK clinicians. A multi-step consultation process. Step 1: a multi-stakeholder steering committee identified key themes of burden, detection and management of cognitive dysfunction in depression, and developed statements on each to explore understanding and degree of agreement among clinicians. Step 2: 100 general practitioners (GPs) and 100 psychiatrists indicated their level of agreement with these statements. Step 3: the steering committee reviewed responses and highlighted priority areas for future education and research. There was agreement that clinicians are not fully aware of cognitive dysfunction in depression. Views of the relationship between cognitive dysfunction and other depressive symptom severities was not consistent with the literature. In particular, there was a lack of recognition that some cognitive dysfunction can persist into remission. There was understandable uncertainty around treatment options, given the current limited evidence base. However, it was recognised that cognitive dysfunction is an area of unmet need and that there is a lack of objective tests of cognition appropriate for depressed patients that can be easily implemented in the clinic. Respondents are likely to be 'led' by the direction of the statements they reviewed. The study did not involve patients and carers. UK clinicians should undergo training regarding cognitive dysfunction in depression, and further research is needed into its assessment, treatment and monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomarkers of sepsis

PubMed Central

2013-01-01

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

Cardio-renal syndromes: a systematic approach for consensus definition and classification.

PubMed

Ronco, Claudio; Ronco, Federico

2012-03-01

The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded to five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Dietary choline requirements of women: effects of estrogen and genetic variation123

PubMed Central

Fischer, Leslie M; da Costa, Kerry-Ann; Kwock, Lester; Galanko, Joseph

2010-01-01

Background: Choline is obtained from the diet and from the biosynthesis of phosphatidylcholine. Phosphatidylcholine is catalyzed by the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which is induced by estrogen. Because they have lower estrogen concentrations, postmenopausal women are more susceptible to the risk of organ dysfunction in response to a low-choline diet. A common genetic polymorphism (rs12325817) in the PEMT gene can also increase this risk. Objective: The objective was to determine whether the risk of low choline–related organ dysfunction increases with the number of alleles of rs12325817 in premenopausal women and whether postmenopausal women (with or without rs12325817) treated with estrogen are more resistant to developing such symptoms. Design: Premenopausal women (n = 27) consumed a choline-sufficient diet followed by a very-low-choline diet until they developed organ dysfunction (or for 42 d), which was followed by a high-choline diet. Postmenopausal women (n = 22) were placed on the same diets but were first randomly assigned to receive estrogen or a placebo. The women were monitored for organ dysfunction and plasma choline metabolites and were genotyped for rs12325817. Results: A dose-response effect of rs12325817 on the risk of choline-related organ dysfunction was observed in premenopausal women: 80%, 43%, and 13% of women with 2, 1, or 0 alleles, respectively, developed organ dysfunction. Among postmenopausal women, 73% who received placebo but only 18% who received estrogen developed organ dysfunction during the low-choline diet. Conclusions: Because of their lower estrogen concentrations, postmenopausal women have a higher dietary requirement for choline than do premenopausal women. Choline requirements for both groups of women are further increased by rs12325817. This trial was registered at clinicaltrials.gov as NCT00065546. PMID:20861172

Dietary choline requirements of women: effects of estrogen and genetic variation.

PubMed

Fischer, Leslie M; da Costa, Kerry-Ann; Kwock, Lester; Galanko, Joseph; Zeisel, Steven H

2010-11-01

Choline is obtained from the diet and from the biosynthesis of phosphatidylcholine. Phosphatidylcholine is catalyzed by the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which is induced by estrogen. Because they have lower estrogen concentrations, postmenopausal women are more susceptible to the risk of organ dysfunction in response to a low-choline diet. A common genetic polymorphism (rs12325817) in the PEMT gene can also increase this risk. The objective was to determine whether the risk of low choline-related organ dysfunction increases with the number of alleles of rs12325817 in premenopausal women and whether postmenopausal women (with or without rs12325817) treated with estrogen are more resistant to developing such symptoms. Premenopausal women (n = 27) consumed a choline-sufficient diet followed by a very-low-choline diet until they developed organ dysfunction (or for 42 d), which was followed by a high-choline diet. Postmenopausal women (n = 22) were placed on the same diets but were first randomly assigned to receive estrogen or a placebo. The women were monitored for organ dysfunction and plasma choline metabolites and were genotyped for rs12325817. A dose-response effect of rs12325817 on the risk of choline-related organ dysfunction was observed in premenopausal women: 80%, 43%, and 13% of women with 2, 1, or 0 alleles, respectively, developed organ dysfunction. Among postmenopausal women, 73% who received placebo but only 18% who received estrogen developed organ dysfunction during the low-choline diet. Because of their lower estrogen concentrations, postmenopausal women have a higher dietary requirement for choline than do premenopausal women. Choline requirements for both groups of women are further increased by rs12325817. This trial was registered at clinicaltrials.gov as NCT00065546.

Early organ-specific mitochondrial dysfunction of jejunum and lung found in rats with experimental acute pancreatitis

PubMed Central

Mittal, Anubhav; Hickey, Anthony JR; Chai, Chau C; Loveday, Benjamin PT; Thompson, Nichola; Dare, Anna; Delahunt, Brett; Cooper, Garth JS; Windsor, John A; Phillips, Anthony RJ

2011-01-01

Introduction Multiple organ dysfunction is the main cause of death in severe acute pancreatitis. Primary mitochondrial dysfunction plays a central role in the development and progression of organ failure in critical illness. The present study investigated mitochondrial function in seven tissues during early experimental acute pancreatitis. Methods Twenty-eight male Wistar rats (463 ± 2 g; mean ± SEM) were studied. Group 1 (n = 8), saline control; Group 2 (n = 6), caerulein-induced mild acute pancreatitis; Group 3 (n = 7) sham surgical controls; and Group 4 (n = 7), taurocholate-induced severe acute pancreatitis. Animals were euthanased at 6 h from the induction of acute pancreatitis and mitochondrial function was assessed in the heart, lung, liver, kidney, pancreas, duodenum and jejunum by mitochondrial respirometry. Results Significant early mitochondrial dysfunction was present in the pancreas, lung and jejunum in both models of acute pancreatitis, however, the Heart, liver, kidney and duodenal mitochondria were unaffected. Conclusions The present study provides the first description of early organ-selective mitochondrial dysfunction in the lung and jejunum during acute pancreatitis. Research is now needed to identify the underlying pathophysiology behind the organ selective mitochondrial dysfunction, and the potential benefits of early mitochondrial-specific therapies in acute pancreatitis. PMID:21492333

Risk of Erectile Dysfunction in Transfusion-naive Thalassemia Men

PubMed Central

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-01-01

Abstract Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities. PMID:25837766

Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

PubMed

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-04-01

Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

[Dysfunctional workplace organization and mobbing. 4 representative cases].

PubMed

Albini, Elisa; Benedetti, Laura; Giordano, S; Punzi, Silvia; Cassitto, Maria Grazia

2003-01-01

Stress and psychological harassment at work are increasing worldwide, according to International Agencies (European Community, NIOSH) and to most authors. To describe typical working situations responsible for distress and mobbing, with the aim of early diagnosis and effectiveness of therapy and rehabilitation. Four cases are reported as representative of dysfunctional organization producing distress and pathology or inducing mobbing behavior or mobbing without clear organization responsibilities. In all cases dysfunctional organization appeared to have played a significant role even though not always a direct one. Also, common characteristics were highlighted in the three cases where mobbing was recognized.

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

PubMed Central

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:21918729

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies.

PubMed

Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Bubeck Wardenburg, Juliane; Fortenberry, James; Zajicek, Anne; Mairson, Emma; Typpo, Katri

2017-03-01

To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

Autoimmune Limbic Encephalitis and Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Lamotrigine-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

PubMed

Ozisik, Lale; Tanriover, Mine Durusu; Saka, Esen

2016-01-01

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug hypersensitivity reaction characterized by rash, fever and multi-organ failure. Limbic encephalitis (LE) is a rare disorder characterized by cognitive dysfunction with memory disturbance, seizures and psychiatric symptoms. We herein present an unusual case of DRESS syndrome due to lamotrigine with reactivation of Epstein-Barr virus, which developed autoimmune LE and syndrome of inappropriate antidiuretic hormone secretion. Discontinuation of lamotrigine, administration of methylprednisolone and intravenous immunoglobulin led to improvement. The LE in this case might have been caused by an autoimmune inflammatory mechanism associated with DRESS syndrome.

ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging hematopoietic stem/progenitor cells in mice

PubMed Central

Chai, Xiao; Li, Deguan; Cao, Xiaoli; Zhang, Yuchen; Mu, Juan; Lu, Wenyi; Xiao, Xia; Li, Chengcheng; Meng, Juanxia; Chen, Jie; Li, Qing; Wang, Jishi; Meng, Aimin; Zhao, Mingfeng

2015-01-01

Iron overload, caused by hereditary hemochromatosis or repeated blood transfusions in some diseases, such as beta thalassemia, bone marrow failure and myelodysplastic syndrome, can significantly induce injured bone marrow (BM) function as well as parenchyma organ dysfunctions. However, the effect of iron overload and its mechanism remain elusive. In this study, we investigated the effects of iron overload on the hematopoietic stem and progenitor cells (HSPCs) from a mouse model. Our results showed that iron overload markedly decreased the ratio and clonogenic function of murine HSPCs by the elevation of reactive oxygen species (ROS). This finding is supported by the results of NAC or DFX treatment, which reduced ROS level by inhibiting NOX4 and p38MAPK and improved the long-term and multi-lineage engrafment of iron overload HSCs after transplantation. Therefore, all of these data demonstrate that iron overload injures the hematopoiesis of BM by enhancing ROS through NOX4 and p38MAPK. This will be helpful for the treatment of iron overload in patients with hematopoietic dysfunction. PMID:25970748

Cognitive Dysfunction in Asian Patients with Depression (CogDAD): A Cross-Sectional Study

PubMed Central

Manit, Srisurapanont; Yee Ming, Mok; Yen Kuang, Yang; Herng-Nieng, Chan; Constantine D, Della; Zuraida, Zainal, Nor; Stephen, Jambunathan; Nurmiati, Amir; Pranabi, Kalita

2017-01-01

Background: Cognitive dysfunction is a predominant symptom of Major Depressive Disorder (MDD), contributing to functional impairment. Objective: The primary objective of this study was to assess and describe perceived cognitive dysfunction amongst Asian patients diagnosed with MDD. The secondary objective was to explore the associations between depression severity, perceived cognitive dysfunction and functional disability. Methods: This was a multi-country, multi-centre, cross-sectional study. Adults with a current episode of MDD were recruited from 9 university/general hospital clinics in Asia. During a single study visit, psychiatrists assessed depression severity (Clinical Global Impression-Severity, CGI-S); patients completed questionnaires assessing depression severity (Patient Health Questionnaire-9 items, PHQ-9), perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D) and functional disability (Sheehan Disability Scale, SDS). Results: Patients (n=664), predominantly women (66.3%), were aged 46.5±12.5 years, lived in urban areas (81.3%) and were employed (84.6%). 51.5% of patients were having their first depressive episode; 86.7% were receiving treatment; 82.2% had a current episode duration >8 weeks. Patients had mild-to-moderate depression (CGI-S=3.3±1.0; PHQ-9=11.3±6.9). Patients reported perceived cognitive dysfunction (PDQ-D=22.6±16.2) and functional disability (SDS=11.3±7.9). PHQ-9, PDQ-D and SDS were moderately-to-highly correlated (PHQ-9 and SDS: r=0.72; PHQ-9 and PDQ-D: r=0.69; PDQ-D and SDS, r=0.63). ANCOVA showed that after controlling for patient-reported depression severity (PHQ-9), perceived cognitive dysfunction (PDQ-D) was significantly associated with functional disability (SDS) (p<0.001). Conclusions: Asian patients with MDD reported perceived cognitive dysfunction. There is a need for physicians to evaluate cognitive dysfunction in the clinical setting in order to reach treatment goals, including functional recovery beyond remission of mood symptoms. PMID:29238395

[Organ damage and cardiorenal syndrome in acute heart failure].

PubMed

Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

2014-03-01

Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Cardiocerebral protection by emulsified isoflurane during cardiopulmonary resuscitation.

PubMed

Zhang, Ya-Jie; Wu, Meng-Jun; Li, Yi; Yu, Hai

2015-01-01

Although improvement in cardiopulmonary resuscitation (CPR) performance and the increasing success at achieving return of spontaneous circulation (ROSC) have been possible in recent years, the survival and discharge rates of post-cardiac arrest (CA) patients remain disappointing. The high mortality rate is attributed to whole-body ischemia/reperfusion (I/R) induced multi-organ dysfunction that is well known as post-cardiac arrest syndrome. Post-cardiac arrest myocardial dysfunction and brain injury are the main clinical features of this complex pathophysiological process. Previous evidences have shown that volatile anesthetics, such as isoflurane, trigger a powerful and highly integrated cell survival response during I/R period in multiple organs, including heart and brain, which reduces I/R injury. This effect that called anesthetic-induced postconditioning can be shown when volatile anesthetics are administered after the onset of ischemia and at the time of reperfusion. Emulsified isoflurane (EIso) is a new anesthetic for intravenous administration, which is conveniently feasible outside operating room. Therefore, we hypothesize that EIso postconditioning could provide the cardiocerebral protection, and combined with therapeutic hypothermia as sedative agent could produce enhanced cardiocerebral protection, which can result in significant improvement of neurologically intact post-cardiac arrest survival. We consider that it would become a feasible, safe and efficient cardiocerebral protective intervention in the prevention and alleviation of post-cardiac arrest syndrome, which would also improve the outcomes after CA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Early Immune Function and Duration of Organ Dysfunction in Critically Ill Septic Children.

PubMed

Muszynski, Jennifer A; Nofziger, Ryan; Moore-Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W

2018-02-22

Late immune suppression is associated with nosocomial infection and mortality in septic adults and children. Relationships between early immune suppression and outcomes in septic children remain unclear. Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis/septic shock. Methods, Measurements and Main Results: Children aged < 18 years meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy controls were sampled once. Innate immune function was quantified by whole blood ex vivo lipopolysaccharide-induced TNFα production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFNγ production capacity. 102 septic children and 35 healthy children were enrolled. Compared to healthy children, septic children demonstrated lower LPS-induced TNFα production (p < 0.0001) and lower PHA-induced IFNγ production (p<0.0001). Among septic children, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction (MODS) and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased MODS days [aRR 1.2 (1.03, 1.5)] and organ dysfunction days [aRR 1.2 (1.1, 1.3)]. Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early suppression of both innate and adaptive immunity are associated with longer duration of organ dysfunction and may be useful markers to guide investigations of immunomodulatory therapies in septic children.

Protocolized Treatment Is Associated With Decreased Organ Dysfunction in Pediatric Severe Sepsis.

PubMed

Balamuth, Fran; Weiss, Scott L; Fitzgerald, Julie C; Hayes, Katie; Centkowski, Sierra; Chilutti, Marianne; Grundmeier, Robert W; Lavelle, Jane; Alpern, Elizabeth R

2016-09-01

To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis. Retrospective cohort study. Tertiary care children's hospital from January 1, 2012, to March 31, 2014. Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included. The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7-10.4). Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

PubMed

Harjola, Veli-Pekka; Mullens, Wilfried; Banaszewski, Marek; Bauersachs, Johann; Brunner-La Rocca, Hans-Peter; Chioncel, Ovidiu; Collins, Sean P; Doehner, Wolfram; Filippatos, Gerasimos S; Flammer, Andreas J; Fuhrmann, Valentin; Lainscak, Mitja; Lassus, Johan; Legrand, Matthieu; Masip, Josep; Mueller, Christian; Papp, Zoltán; Parissis, John; Platz, Elke; Rudiger, Alain; Ruschitzka, Frank; Schäfer, Andreas; Seferovic, Petar M; Skouri, Hadi; Yilmaz, Mehmet Birhan; Mebazaa, Alexandre

2017-07-01

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Continuous hemoadsorption with a cytokine adsorber during sepsis - a review of the literature.

PubMed

Houschyar, Khosrow S; Pyles, Malcolm N; Rein, Susanne; Nietzschmann, Ina; Duscher, Dominik; Maan, Zeshaan N; Weissenberg, Kristian; Philipps, Hubertus M; Strauss, Catharina; Reichelt, Beate; Siemers, Frank

2017-05-29

Sepsis is a well-recognized healthcare issue worldwide, ultimately resulting in significant mortality, morbidity and resource utilization during and after critical illness. In its most severe form, sepsis causes multi-organ dysfunction that produces a state of critical illness characterized by severe immune dysfunction and catabolism. Sepsis induces the activation of complement factor via 3 pathways and the release of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β), resulting in a systemic inflammatory response. The inflammatory cytokines and nitric oxide release induced by sepsis decrease systemic vascular resistance, resulting in profound hypotension. The combination of hypotension and microvascular occlusion results in tissue ischemia and ultimately leads to multiple organ failure. Several clinical and experimental studies have reported that treatment using adsorption of cytokines is beneficial during endotoxemia and sepsis. This review article analyzes the efficacy of CytoSorb® adsorber in reducing the inflammatory response during sepsis. The CytoSorb® adsorber is known to have excellent adsorption rates for inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, and TNF-α. Studies have demonstrated that treatment with cytokine adsorbing columns has beneficial effects on the survival rate and inflammatory responses in animal septic models. Additionally, several cases have been reported in which treatment with cytokine adsorbing columns is very effective in hemodynamic stabilization and in preventing organ failure in critically ill patients. Although further investigations and clinical trials are needed, treatment with cytokine adsorbing columns may play an important role in the treatment of sepsis in the near future.

Mitochondrial DNA Damage Initiates Acute Lung Injury and Multi-Organ System Failure Evoked in Rats by Intra-Tracheal Pseudomonas Aeruginosa.

PubMed

Lee, Yann-Leei; Obiako, Boniface; Gorodnya, Olena M; Ruchko, Mykhaylo V; Kuck, Jamie L; Pastukh, Viktor M; Wilson, Glenn L; Simmons, Jon D; Gillespie, Mark N

2017-07-01

Although studies in rat cultured pulmonary artery endothelial cells, perfused lungs, and intact mice support the concept that oxidative mitochondrial (mt) DNA damage triggers acute lung injury (ALI), it has not yet been determined whether enhanced mtDNA repair forestalls development of ALI and its progression to multiple organ system failure (MOSF). Accordingly, here we examined the effect of a fusion protein construct targeting the DNA glycosylase, Ogg1, to mitochondria in a rat model intra-tracheal Pseudomonas aeruginosa (strain 103; PA103)-induced ALI and MOSF. Relative to controls, animals given PA103 displayed increases in lung vascular filtration coefficient accompanied by transient lung tissue oxidative mtDNA damage and variable changes in mtDNA copy number without evidence of nuclear DNA damage. The approximate 40% of animals surviving 24 h after bacterial administration exhibited multiple organ dysfunction, manifest as increased serum and tissue-specific indices of kidney and liver failure, along with depressed heart rate and blood pressure. While administration of mt-targeted Ogg1 to control animals was innocuous, the active fusion protein, but not a DNA repair-deficient mutant, prevented bacteria-induced increases in lung tissue oxidative mtDNA damage, failed to alter mtDNA copy number, and attenuated lung endothelial barrier degradation. These changes were associated with suppression of liver, kidney, and cardiovascular dysfunction and with decreased 24 h mortality. Collectively, the present findings indicate that oxidative mtDNA damage to lung tissue initiates PA103-induced ALI and MOSF in rats.

Acute kidney injury in critically ill child.

PubMed

Al-Jboor, Wejdan; Almardini, Reham; Al Bderat, Jwaher; Frehat, Mahdi; Al Masri, Hazem; Alajloni, Mohammad Saleh

2016-01-01

Acute kidney injury (AKI) is a common and serious complication in patients in the Pediatric Intensive Care Unit (PICU). We conducted this study to estimate the incidence and the mortality rate of AKI in critically ill children as well as to describe some other related factors. A retrospective study was conducted at PICU of Queen Rania Abdulla Children Hospital, Amman, Jordan for the period extending from May 2011 to June 2013. The medical records of all patients admitted during this period, and their demographic data were reviewed. Patients with AKI were identified, and management and outcomes were reviewed and analyzed. AKI was evaluated according to modified RIFLE criteria. Of the 372 patients admitted to PICU, 64 (17.2%) patients developed AKI. Of these 64 patients who had AKI, 28 (43.7%) patients reached RIFLE max of risk, 21 (32.8%) patients reached injury, and 15 (23.4%) reached failure. Mean Pediatric Risk of Mortality II score at admission was significantly higher in patients with AKI than those without P <0.001. The age ranged between one month and 14 years with the median age as 5.4 year. Thirty-five (54.7%) were males. Sepsis was the most common cause of AKI. The mortality rate in critically ill children without AKI was 58.7%, whereas increased in children with AKI to 73.4%. The mortality rate in patients who received renal replacement therapy was 71.4% and was higher (81.5%) in patients who received mechanical ventilation (95%, [confidence interval (CI)] 79.3-83.4%) and was significantly higher in patients with multi-organ system dysfunction 90.3% (95%, [CI] 88.7-92.5%). The incidence of AKI in critically ill children is high and increased their mortality rate and higher mortality seen in the younger age group, especially those below one year. High mortality rate was associated with multi-organ system dysfunction and the need for mechanical ventilation.

The budget impact and cost-effectiveness of defibrotide for treatment of veno-occlusive disease with multi-organ dysfunction in patients post-hematopoietic stem cell transplant.

PubMed

Veenstra, David L; Guzauskas, Gregory F; Villa, Kathleen F; Boudreau, Denise M

2017-05-01

A Phase-3 study of defibrotide compared with historical controls demonstrated a 23% improvement in 100-day survival post-hematopoietic stem cell transplantation (HSCT) among patients with veno-occlusive disease with multi-organ dysfunction (VOD with MOD). To estimate the budget impact and cost-effectiveness of introducing defibrotide to a transplant center. The authors developed a budget impact model from the perspective of a bone-marrow transplant center. It was estimated that 2.3% of adults and 4.2% of children would develop VOD with MOD following HSCT based on a retrospective hospital database analysis and the effect that treating patients with defibrotide would have on costs for adult and pediatric centers was estimated. A cost-utility analysis (CUA) was also developed to capture the long-term cost-effectiveness of defibrotide. Projected life expectancies in the two groups were estimated based on trial data, transplant registry data, studies of long-term survival among HSCT patients, and US population life-tables. There was an estimated 3% increase ($330,706) per year in total adult transplantation center costs associated with adopting defibrotide, and a <1% increase ($106,385) for pediatric transplant centers, assuming 100 transplants per year. In the CUA, the lifetime increase in cost per patient was $106,928, life expectancy increased by 3.74 years, and quality-adjusted life-years (QALYs) increased by 2.24. The incremental cost-effectiveness ratio (ICER) was $47,736 per QALY gained; 88% probability defibrotide was cost-effective at a $100,000/QALY threshold. The budget impact of defibrotide for a transplant center is relatively modest compared to the overall cost of transplantation. Defibrotide provides an important survival advantage for VOD with MOD patients, and the life years gained lead to defibrotide being highly cost-effective.

The diagnosis and management of progressive dysfunction of health care organizations.

PubMed

Chervenak, Frank A; McCullough, Laurence B

2005-04-01

This paper presents an ethically justified approach to the diagnosis and management of progressive dysfunction of health care organizational cultures. We explain the concept of professional integrity in terms of the ethical concept of the cofiduciary responsibility of physicians and health care organizations. We identify the ethical features of a healthy health care organization and the spectrum of progressive dysfunction of organizational cultures from cynical through wonderland and Kafkaesque to postmodern. Physicians should respond to cynical health care organizations by creating moral enclaves of professional integrity for the main purpose of confrontation and reform, to wonderland organizations by strengthening moral enclaves for the main purpose of resisting self-deception, to Kafkaesque organizations by strengthening moral enclaves still further for the main purpose of defending professional integrity (adopting a Machiavellian appearance of virtue as necessary), and to postmodern organizations by creating moral fortresses and, should these fail, quitting.

Biology of sepsis: its relevance to pediatric nephrology.

PubMed

Blatt, Neal B; Srinivasan, Sushant; Mottes, Theresa; Shanley, Maureen M; Shanley, Thomas P

2014-12-01

Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas.

Bioactivation of organic nitrates and the mechanism of nitrate tolerance.

PubMed

Klemenska, Emila; Beresewicz, Andrzej

2009-01-01

Organic nitrates, such as nitroglycerin, are commonly used in the therapy of cardiovascular disease. Long-term therapy with these drugs, however, results in the rapid development of nitrate tolerance, limiting their hemodynamic and anti-ischemic efficacy. In addition, nitrate tolerance is associated with the expression of potentially deleterious modifications such as increased oxidative stress, endothelial dysfunction, and sympathetic activation. In this review we discuss current concepts regarding the mechanisms of organic nitrate bioactivation, nitrate tolerance, and nitrate-mediated oxidative stress and endothelial dysfunction. We also examine how hydralazine may prevent nitrate tolerance and related endothelial dysfunction.

Xenotransplantation of porcine islet cells as a potential option for the treatment of type 1 diabetes in the future.

PubMed

Reichart, B; Niemann, H; Chavakis, T; Denner, J; Jaeckel, E; Ludwig, B; Marckmann, G; Schnieke, A; Schwinzer, R; Seissler, J; Tönjes, R R; Klymiuk, N; Wolf, E; Bornstein, S R

2015-01-01

Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation. A major strength of this consortium is the inclusion of members of the regulatory bodies, including the Paul-Ehrlich Institute (PEI), infection specialists from the Robert Koch Institute and PEI, veterinarians from the German Primate Center, and representatives of influential ethical and religious institutions. A major goal of this consortium is to promote islet xenotransplantation, based on the extensive expertise and experience of the existing clinical islet transplantation program. Besides comprehensive approaches to understand and prevent inflammation-mediated islet xenotransplant dysfunction [immediate blood-mediated inflammatory reaction (IBMIR)], we also take advantage of the availability of and experience with islet macroencapsulation, with the goal to improve graft survival and function. This consortium harbors a unique group of scientists with complementary expertise under a cohesive program aiming at developing new therapeutic approaches for islet replacement and solid organ xenotransplantation. © Georg Thieme Verlag KG Stuttgart · New York.

Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis.

PubMed

Maestraggi, Quentin; Lebas, Benjamin; Clere-Jehl, Raphaël; Ludes, Pierre-Olivier; Chamaraux-Tran, Thiên-Nga; Schneider, Francis; Diemunsch, Pierre; Geny, Bernard; Pottecher, Julien

2017-01-01

Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called "cytopathic hypoxia," perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system ("immunoparalysis") translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

Effectiveness of physical exam signs for early detection of critical illness in pediatric systemic inflammatory response syndrome.

PubMed

Scott, Halden F; Donoghue, Aaron J; Gaieski, David F; Marchese, Ronald F; Mistry, Rakesh D

2014-11-19

Early detection of compensated pediatric septic shock requires diagnostic tests that are sensitive and specific. Four physical exam signs are recommended for detecting pediatric septic shock prior to hypotension (cold extremities, mental status, capillary refill, peripheral pulse quality); this study tested their ability to detect patients who develop organ dysfunction among a cohort of undifferentiated pediatric systemic inflammatory response syndrome patients. A prospective cohort of 239 pediatric emergency department patients <19 years with fever and tachycardia and undergoing phlebotomy were enrolled. Physicians recorded initial physical exams on a standardized form. Abstraction of the medical record determined outcomes including organ dysfunction, intensive care unit stay, serious bacterial infection, and therapies. Organ dysfunction occurred in 13/239 (5.4%) patients. Presence of at least one sign was significantly associated with organ dysfunction (Relative Risk: 2.71, 95% CI: 1.05-6.99), and presence of at least two signs had a Relative Risk = 4.98 (95% CI: 1.82-13.58). The sensitivity of exam findings ranged from 8-54%, specificity from 84-98%. Signs were associated with increased risk of intensive care and fluid bolus, but not with serious bacterial infection, intravenous antibiotics or admission. Altered mental status and peripheral pulse quality were significantly associated with organ dysfunction, while abnormal capillary refill time and presence of cold, mottled extremities were not. Certain recommended physical exam signs were associated with increased risk of organ dysfunction, a rare outcome in this undifferentiated pediatric population with fever and tachycardia. Sensitivity was low, while specificity was high. Additional research into optimally sensitive and specific diagnostic strategies is needed.

A comparison of three organ dysfunction scores: MODS, SOFA and LOD for predicting ICU mortality in critically ill patients.

PubMed

Khwannimit, Bodin

2007-06-01

To compare the validity of the Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), and Logistic Organ Dysfunction Score (LOD) for predicting ICU mortality of Thai critically ill patients. A retrospective study was made of prospective data collected between the 1st July 2004 and 31st March 2006 at Songklanagarind Hospital. One thousand seven hundred and eighty two patients were enrolled in the present study. Two hundred and ninety three (16.4%) deaths were recorded in the ICU. The areas under the Receiver Operating Curves (A UC) for the prediction of ICU mortality the results were 0.861 for MODS, 0.879 for SOFA and 0.880 for LOD. The AUC of SOFA and LOD showed a statistical significance higher than the MODS score (p = 0.014 and p = 0.042, respectively). Of all the models, the neurological failure score showed the best correlation with ICU mortality. All three organ dysfunction scores satisfactorily predicted ICU mortality. The LOD and neurological failure had the best correlation with ICU outcome.

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma

PubMed Central

Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M.; Messerer, David A. C.; Radermacher, Peter; Kalbitz, Miriam; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

2015-01-01

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction. PMID:26556956

Functional Turnover: An Empirical Assessment.

DTIC Science & Technology

1981-08-01

assumption that turnover is invariably dysfunctional to the organization (Dalton & Todor , 1979; Dalton & Todor , in press (a), (b); Jeswald, 1974; Muchinsky...34voluntary" turnover (Dalton, Todor & Krackhardt, in press). Dysfunctional (cell C) - The individual wants to leave the organization but the organization...criticized (Dalton & Todor , 1979; Dalton & Todor . in press (a), (b); Muchinsky & Tuttle, 1979; Muchinsky & Morrow, in press; Staw, in press; Staw

Central insulin and leptin-mediated autonomic control of glucose homeostasis

PubMed Central

Marino, Joseph S.; Xu, Yong; Hill, Jennifer W.

2016-01-01

Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. PMID:21489811

Central insulin and leptin-mediated autonomic control of glucose homeostasis.

PubMed

Marino, Joseph S; Xu, Yong; Hill, Jennifer W

2011-07-01

Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Inflammatory response and extracorporeal circulation.

PubMed

Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander

2015-06-01

Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of experimental rat model of multiple organ dysfunction on cefepime and amikacin pharmacokinetics.

PubMed Central

Mimoz, O; Jacolot, A; Padoin, C; Quillard, J; Tod, M; Louchahi, K; Samii, K; Petitjean, O

1996-01-01

We adapted an experimental model of multiple organ dysfunction to study the alterations it induces in the pharmacology of cefepime and amikacin. The half-lives of both antibiotics were significantly prolonged because of nonsignificant enhancement of the volume of distribution and reduced renal elimination. In the presence of multiple organ dysfunction, the concentration of each antibiotic in the lungs, compared with that in the lungs of healthy controls, was significantly decreased, despite similar concentrations in plasma, indicating that the application of a standard antibiotic concentration in plasma could lead to underdosage in tissues during the initial days of therapy. PMID:8851623

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling

PubMed Central

Dick, Thomas E.; Molkov, Yaroslav I.; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J.; Doyle, John; Scheff, Jeremy D.; Calvano, Steve E.; Androulakis, Ioannis P.; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. PMID:22783197

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

PubMed

Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

PATHOPHYSIOLOGY AND THE CARDIORENAL CONNECTION IN HEART FAILURE. CIRCULATING HORMONES: BIOMARKERS OR MEDIATORS

PubMed Central

BUGLIONI, ALESSIA; BURNETT, JOHN C.

2014-01-01

Heart failure (HF) is a syndrome characterized by a complex pathophysiology which involves multiple organ systems, with the kidney playing a major role. HF can present with reduced ejection fraction (EF), HFrEF, or with preserved EF (HFpEF). The interplay between diverse organ systems contributing to HF is mediated by the activation of counteracting neurohormonal pathways focused to re-establishing hemodynamic homeostasis. During early stages of HF, these biochemical signals, consisting mostly of hormones and neurotransmitters secreted by a variety of cell types, are compensatory and the patient is asymptomatic. However, with disease progression, the attempt to reverse or delay cardiac dysfunction is deleterious, leading to multi-organ congestion, fibrosis and decompensation and finally symptomatic HF. In conclusion, these neurohormonal pathways mediate the evolution of HF and have become a way to monitor HF. Specifically, these mediators have become important in the diagnosis and prognosis of this highly fatal cardiovascular disease. Finally, while these multiple neurohumoral factors serve as important HF biomarkers, they can also be targeted for more effective and curative HF treatments. PMID:25445413

Magnetic resonance imaging correlates of bee sting induced multiple organ dysfunction syndrome: A case report.

PubMed

Das, Sushant K; Zeng, Li-Chuan; Li, Bing; Niu, Xiang-Ke; Wang, Jing-Liang; Bhetuwal, Anup; Yang, Han-Feng

2014-09-28

Occasionally systemic complications with high risk of death, such as multiple organ dysfunction syndrome (MODS), can occur following multiple bee stings. This case study reports a patient who presented with MODS, i.e., acute kidney injury, hepatic and cardiac dysfunction, after multiple bee stings. The standard clinical findings were then correlated with magnetic resonance imaging (MRI) findings, which demonstrates that MRI may be utilized as a simpler tool to use than other multiple diagnostics.

Predictors of Olfactory Dysfunction in Rhinosinusitis Using the Brief Smell Identification Test

PubMed Central

Alt, Jeremiah A.; Mace, Jess C.; Buniel, Maria C. F.; Soler, Zachary M.; Smith, Timothy L.

2014-01-01

Objective Associations between olfactory function to quality-of-life (QOL) and disease severity in patients with rhinosinusitis is poorly understood. We sought to evaluate and compare olfactory function between subgroups of patients with rhinosinusitis using the Brief Smell Identification Test (BSIT). Study Design Cross-sectional evaluation of a multi-center cohort. Methods Patients with recurrent acute sinusitis (RARS) and chronic rhinosinusitis (CRS) with and without nasal polyposis were prospectively enrolled from three academic tertiary care sites. Each subject completed the BSIT, in addition to measures of disease-specific QOL. Patient demographics, comorbidities, and clinical measures of disease severity were compared between patients with normal (BSIT; ≥9) and abnormal (BSIT; <9) olfaction scores. Regression modeling was used to identify potential risk factors associated with olfactory impairment. Results Patients with rhinosinusitis (n=445) were found to suffer olfactory dysfunction as measured by the BSIT (28.3%). Subgroups of rhinosinusitis differed in the degree of olfactory dysfunction reported. Worse disease severity, measured by computed tomography and nasal endoscopy, correlated to worse olfaction. Olfactory scores did not consistently correlate with Rhinosinusitis Disability Index or Sinonasal Outcome Test scores. Regression models demonstrated nasal polyposis was the strongest predictor of olfactory dysfunction. Recalcitrant disease and aspirin intolerance were strongly predictive of worse olfactory function. Conclusion Olfactory dysfunction is a complex, multi-factorial process found to be differentially expressed within subgroups of rhinosinusitis. Olfaction was associated with disease severity as measured by imaging and endoscopy, with only weak associations to disease-specific QOL measures. PMID:24402746

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

PubMed Central

2010-01-01

Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

PubMed

Witteveen, Tom; Bezstarosti, Hans; de Koning, Ilona; Nelissen, Ellen; Bloemenkamp, Kitty W; van Roosmalen, Jos; van den Akker, Thomas

2017-06-19

WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Identifying and Extinguishing Dysfunctional and Deadly Organizational Practices

ERIC Educational Resources Information Center

Mawhinney, Thomas C.

2009-01-01

It is possible to define an organization's culture in terms of its dominant behavioral practices and their molar consequences, from the shop floor to the executive suite (Redmon & Mason, 2001). Dysfunctional and potentially deadly practices (for the organization as a whole) can be "latent." They often go undetected until their…

Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Opdahl, Anders; Venkatesh, Bharath Ambale; Fernandes, Veronica R. S.; Wu, Colin O.; Nasir, Khurram; Choi, Eui-Young; Almeida, Andre L. C.; Rosen, Boaz; Carvalho, Benilton; Edvardsen, Thor; Bluemke, David A.; Lima, Joao A. C.

2014-01-01

OBJECTIVE To investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function is not well described in an asymptomatic multi-ethnic population. METHODS Participants in the Multi-Ethnic Study of Atherosclerosis had resting heart rate measured at inclusion. Incident HF was registered (n=176) during follow-up (median 7 years) in those who underwent cardiac MRI (n=5000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 bpm increase in resting heart rate there was a 4% greater adjusted relative risk for incident HF (Hazard Ratio: 1.04 (1.02, 1.06 (95% CI); P<0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even in analyses when all coronary heart disease events were excluded from the model. CONCLUSION Elevated resting heart rate is associated with increased risk for incident HF in asymptomatic participants in MESA. Higher heart rate is related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. PMID:24412444

Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.

PubMed

Richardson, Paul G; Triplett, Brandon M; Ho, Vincent T; Chao, Nelson; Dignan, Fiona L; Maglio, Michelle; Mohty, Mohamad

2018-02-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered: Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States. Its efficacy in patients with VOD/SOS with MOD post-HSCT was demonstrated in a clinical-trial program that included a historically controlled treatment study, a phase 2 trial, and a large T-IND expanded-access program that also included patients without MOD and who received chemotherapy without HSCT. Expert commentary: Defibrotide appears to protect endothelial cells and restore the thrombolytic-fibrinolytic balance. It addresses a significant clinical need and has demonstrated favorable Day +100 survival and overall adverse-event rates that seem similar to control groups receiving supportive care alone. Currently, defibrotide is under investigation for the prevention of VOD/SOS in high-risk pediatric and adult patients.

Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure

PubMed Central

Dear, James W.; Leelahavanichkul, Asada; Aponte, Angel; Hu, Xuzhen; Constant, Stephanie L.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Objective Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and, therefore, identify new drug targets. Design Proteomic discovery study and drug target validation Setting Research institute laboratory Subjects Three month old C57BL/6 mice Interventions We used a mouse model of sepsis based on cecal ligation and puncture (CLP) but with fluid and antibiotic resuscitation. Liver proteins that changed in abundance were identified by difference in-gel electrophoresis (DIGE). We compared liver proteins from 6 hr post-CLP to sham-operated mice (‘early proteins’) and 24 hr post-CLP with 6 hr post-CLP (‘late proteins’). Proteins that changed in abundance were identified by tandem mass spectrometry. We then inhibited the receptor for one protein and determined the effect on sepsis-induced organ dysfunction. Results The liver proteins that changed in abundance after sepsis had a range of functions such as acute phase proteins, coagulation, ER stress, oxidative stress, apoptosis, mitochondrial proteins and nitric oxide metabolism. We found that cyclophilin increased in abundance after CLP. When the receptor for this protein, CD147, was inhibited sepsis-induced renal dysfunction was reduced. There was also a significant reduction in serum cytokine production when CD147 was inhibited. Conclusion By applying proteomics to a clinically relevant mouse model of sepsis we identified a number of novel proteins that changed in abundance. The inhibition of the receptor for one of these proteins, cyclophilin, attenuated sepsis-induced acute renal failure. The application of proteomics to sepsis research can facilitate the discovery of new therapeutic targets. PMID:17944020

Serial evaluation of the MODS, SOFA and LOD scores to predict ICU mortality in mixed critically ill patients.

PubMed

Khwannimit, Bodin

2008-09-01

To perform a serial assessment and compare ability in predicting the intensive care unit (ICU) mortality of the multiple organ dysfunction score (MODS), sequential organ failure assessment (SOFA) and logistic organ dysfunction (LOD) score. The data were collected prospectively on consecutive ICU admissions over a 24-month period at a tertiary referral university hospital. The MODS, SOFA, and LOD scores were calculated on initial and repeated every 24 hrs. Two thousand fifty four patients were enrolled in the present study. The maximum and delta-scores of all the organ dysfunction scores correlated with ICU mortality. The maximum score of all models had better ability for predicting ICU mortality than initial or delta score. The areas under the receiver operating characteristic curve (AUC) for maximum scores was 0.892 for the MODS, 0.907 for the SOFA, and 0.92for the LOD. No statistical difference existed between all maximum scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Serial assessment of organ dysfunction during the ICU stay is reliable with ICU mortality. The maximum scores is the best discrimination comparable with APACHE II score in predicting ICU mortality.

The prognostic and risk-stratified value of heart-type fatty acid-binding protein in septic patients in the emergency department.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2014-08-01

To evaluate the prognostic and risk-stratified ability of heart-type fatty acid-binding protein (H-FABP) in septic patients in the emergency department (ED). From August to November 2012, 295 consecutive septic patients were enrolled. Circulating H-FABP was measured. The predictive value of H-FABP for 28-day mortality, organ dysfunction on ED arrival, and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was assessed by the receiver operating characteristic curve and logistic regression and was compared with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Mortality in Emergency Department Sepsis (MEDS) score, and Sequential Organ Failure Assessment score. The 28-day mortality, APACHE II, MEDS, and Sequential Organ Failure Assessment scores were much higher in H-FABP-positive patients. The incidence of organ dysfunction at ED arrival and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was higher in H-FABP-positive patients. Heart-type fatty acid-binding protein was an independent predictor of 28-day mortality and organ dysfunction. The area under the receiver operating characteristic curve for H-FABP predicting 28-day mortality and organ dysfunction was 0.784 and 0.755, respectively. Combination of H-FABP and MEDS improved the performance of MEDS in predicting organ dysfunction, and the difference of AUC was statistically significant (P<.05). The combinations of H-FABP and MEDS or H-FABP and APACHE II also improved the prognostic value of MEDS and APACHE II, but the areas under the curve were not statistically different. Heart-type fatty acid-binding protein was helpful for prognosis and risk stratification of septic patients in the ED. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes

PubMed Central

Makris, Konstantinos; Spanou, Loukia

2016-01-01

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI. PMID:28303073

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

PubMed

Makris, Konstantinos; Spanou, Loukia

2016-05-01

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

PubMed Central

Jiang, Peng; Scarpa, Joseph R.; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D.; Hao, Ke; Summa, Keith C.; Yang, He S.; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H.; Turek, Fred W.; Kasarskis, Andrew

2016-01-01

SUMMARY Sleep dysfunction and stress susceptibility are co-morbid complex traits, which often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multi-level organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J×A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests the interplay between sleep, stress, and neuropathology emerge from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework to interrogate the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. PMID:25921536

Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

PubMed Central

Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

2013-01-01

Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis. PMID:23381720

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

PubMed Central

Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

PubMed

Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

Respiratory exacerbation in a young adult with cystic fibrosis and tricuspid atresia.

PubMed

Wood, Jamie; Sawyer, Abbey; Mulrennan, Siobhain; Bullock, Andrew

2018-07-01

Tricuspid atresia (TAt) is a complex congenital heart defect (CHD) characterized by the absence of the tricuspid valve and right ventricular hypoplasia requiring surgery in childhood, the Fontan procedure. We present a case of a 21-year-old male with TAt and cystic fibrosis (CF), who underwent a Fontan procedure in childhood, presenting to an adult CF clinic with severe deterioration in his respiratory status and multi-organ dysfunction associated with CF. This report describes problems associated with the management of a CF respiratory exacerbation and extrapulmonary manifestations of CF in the unique situation of a Fontan circulation, a circulation with absence of a subpulmonary ventricle and pulsatile pulmonary arterial blood flow where maintenance of systemic cardiac output is totally dependent on good respiratory function and low pulmonary artery pressures.

Cross disease analysis of co-functional microRNA pairs on a reconstructed network of disease-gene-microRNA tripartite.

PubMed

Peng, Hui; Lan, Chaowang; Zheng, Yi; Hutvagner, Gyorgy; Tao, Dacheng; Li, Jinyan

2017-03-24

MicroRNAs always function cooperatively in their regulation of gene expression. Dysfunctions of these co-functional microRNAs can play significant roles in disease development. We are interested in those multi-disease associated co-functional microRNAs that regulate their common dysfunctional target genes cooperatively in the development of multiple diseases. The research is potentially useful for human disease studies at the transcriptional level and for the study of multi-purpose microRNA therapeutics. We designed a computational method to detect multi-disease associated co-functional microRNA pairs and conducted cross disease analysis on a reconstructed disease-gene-microRNA (DGR) tripartite network. The construction of the DGR tripartite network is by the integration of newly predicted disease-microRNA associations with those relationships of diseases, microRNAs and genes maintained by existing databases. The prediction method uses a set of reliable negative samples of disease-microRNA association and a pre-computed kernel matrix instead of kernel functions. From this reconstructed DGR tripartite network, multi-disease associated co-functional microRNA pairs are detected together with their common dysfunctional target genes and ranked by a novel scoring method. We also conducted proof-of-concept case studies on cancer-related co-functional microRNA pairs as well as on non-cancer disease-related microRNA pairs. With the prioritization of the co-functional microRNAs that relate to a series of diseases, we found that the co-function phenomenon is not unusual. We also confirmed that the regulation of the microRNAs for the development of cancers is more complex and have more unique properties than those of non-cancer diseases.

Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015.

PubMed

McCabe, Marita P; Sharlip, Ira D; Lewis, Ron; Atalla, Elham; Balon, Richard; Fisher, Alessandra D; Laumann, Edward; Lee, Sun Won; Segraves, Robert T

2016-02-01

This article presents a review of previous research concerning risk factors for sexual dysfunction in women and men. The aim is to evaluate past research studies to determine the contribution of all risk factors to the development and maintenance of sexual dysfunction among women and men. Studies were organized under a biopsychosocial framework, with the bulk of studies of women and men having investigated the role of biological factors. The outcome measures were the data on factors for sexual dysfunction. Many more studies investigated risk factors for sexual dysfunction in men than in women. For women and men, diabetes, heart disease, urinary tract disorders, and chronic illness were significant risk factors for sexual dysfunction. Depression and anxiety and the medications used to treat these disorders also were risk factors for sexual dysfunction in women and men. In addition, substance abuse was associated with sexual dysfunction. Many other social and cultural factors were related to sexual dysfunction in women and men. Psychosocial factors are clearly risk factors for sexual dysfunction. Women and men with sexual dysfunction should be offered psychosocial evaluation and treatment, if available, in addition to medical evaluation and treatment. The impact of social and cultural factors on sexual function requires substantially more research. The evidence that erectile dysfunction is a harbinger of other forms of cardiovascular disease is strong enough to recommend that clinical evaluation for occult cardiovascular disease should be undertaken in men who do not have known cardiovascular disease but who develop organic erectile dysfunction, especially in men younger than 70 years. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

PubMed Central

Conway, Christopher C.; Slavich, George M.; Hammen, Constance

2016-01-01

Despite decades of research examining diathesis-stress models of emotional disorders, it remains unclear whether dysfunctional attitudes interact with stressful experiences to shape affect on a daily basis and, if so, how clinical and genetic factors influence these associations. To address these issues, we conducted a multi-level daily diary study that examined how dysfunctional attitudes and stressful events relate to daily fluctuations in negative and positive affect in 104 young adults. Given evidence that clinical and genetic factors underlie stress sensitivity, we also examined how daily affect is influenced by internalizing and externalizing symptoms and brain-derived neurotrophic factor (BDNF) genotype, which have been shown to influence neural, endocrine, and affective responses to stress. In multivariate models, internalizing symptoms and BDNF Val66Met genotype independently predicted heightened negative affect on stressful days, but dysfunctional attitudes did not. Specifically, the BDNF Met allele and elevated baseline internalizing symptomatology predicted greater increases in negative affect in stressful circumstances. These data are the first to demonstrate that BDNF genotype and stress are jointly associated with daily fluctuations in negative affect, and they challenge the assumption that maladaptive beliefs play a strong independent role in determining affective responses to everyday stressors. The results may thus inform the development of new multi-level theories of psychopathology and guide future research on predictors of affective lability. PMID:27041782

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement.

PubMed

Kotloff, Robert M; Blosser, Sandralee; Fulda, Gerard J; Malinoski, Darren; Ahya, Vivek N; Angel, Luis; Byrnes, Matthew C; DeVita, Michael A; Grissom, Thomas E; Halpern, Scott D; Nakagawa, Thomas A; Stock, Peter G; Sudan, Debra L; Wood, Kenneth E; Anillo, Sergio J; Bleck, Thomas P; Eidbo, Elling E; Fowler, Richard A; Glazier, Alexandra K; Gries, Cynthia; Hasz, Richard; Herr, Dan; Khan, Akhtar; Landsberg, David; Lebovitz, Daniel J; Levine, Deborah Jo; Mathur, Mudit; Naik, Priyumvada; Niemann, Claus U; Nunley, David R; O'Connor, Kevin J; Pelletier, Shawn J; Rahman, Omar; Ranjan, Dinesh; Salim, Ali; Sawyer, Robert G; Shafer, Teresa; Sonneti, David; Spiro, Peter; Valapour, Maryam; Vikraman-Sushama, Deepak; Whelan, Timothy P M

2015-06-01

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

inactivate) circulating histones and prevent the morbidity and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome ...patients. 15. SUBJECT TERMS Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome , extracellular...are acute lung injury (ALI) from smoke/chlorine gas inhalation, burns, radiation , influenza and severe infection. Only recently have investigators

Oral Disease Profiles in Chronic Graft versus Host Disease

PubMed Central

Fassil, H.; Mays, J.W.; Edwards, D.; Baird, K.; Steinberg, S.M.; Cowen, E.W.; Naik, H.; Datiles, M.; Stratton, P.; Gress, R.E.; Pavletic, S.Z.

2015-01-01

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer’s tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. PMID:25740857

Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome.

PubMed

Wada, Takeshi; Jesmin, Subrina; Gando, Satoshi; Yanagida, Yuichiro; Mizugaki, Asumi; Sultana, Sayeeda N; Zaedi, Sohel; Yokota, Hiroyuki

2012-09-29

Post-cardiac arrest syndrome (PCAS) often leads to multiple organ dysfunction syndrome (MODS) with a poor prognosis. Endothelial and leukocyte activation after whole-body ischemia/reperfusion following resuscitation from cardiac arrest is a critical step in endothelial injury and related organ damage. Angiogenic factors, including vascular endothelial growth factor (VEGF) and angiopoietin (Ang), and their receptors play crucial roles in endothelial growth, survival signals, pathological angiogenesis and microvascular permeability. The aim of this study was to confirm the efficacy of angiogenic factors and their soluble receptors in predicting organ dysfunction and mortality in patients with PCAS. A total of 52 resuscitated patients were divided into two subgroups: 23 survivors and 29 non-survivors. The serum levels of VEGF, soluble VEGF receptor (sVEGFR)1, sVEGFR2, Ang1, Ang2 and soluble Tie2 (sTie2) were measured at the time of admission (Day 1) and on Day 3 and Day 5. The ratio of Ang2 to Ang1 (Ang2/Ang1) was also calculated. This study compared the levels of angiogenic factors and their soluble receptors between survivors and non-survivors, and evaluated the predictive value of these factors for organ dysfunction and 28-day mortality. The non-survivors demonstrated more severe degrees of organ dysfunction and a higher prevalence of MODS. Non-survivors showed significant increases in the Ang2 levels and the Ang2/Ang1 ratios compared to survivors. A stepwise logistic regression analysis demonstrated that the Ang2 levels or the Ang2/Ang1 ratios on Day 1 independently predicted the 28-day mortality. The receiver operating characteristic curves of the Ang2 levels, and the Ang2/Ang1 ratios on Day 1 were good predictors of 28-day mortality. The Ang2 levels also independently predicted increases in the Sequential Organ Failure Assessment (SOFA) scores. We observed a marked imbalance between Ang1 and Ang2 in favor of Ang2 in PCAS patients, and the effect was more prominent in non-survivors. Angiogenic factors and their soluble receptors, particularly Ang2 and Ang2/Ang1, are considered to be valuable predictive biomarkers in the development of organ dysfunction and poor outcomes in PCAS patients.

Jet Fuel Exacerbated Noise-Induced Hearing Loss: Focus on Prediction of Central Auditory Processing Dysfunction

DTIC Science & Technology

2017-09-01

to develop a multi-scale model, together with relevant supporting experimental data, to describe jet fuel exacerbated noise induced hearing loss. In...scale model, together with relevant supporting experimental data, to describe jet fuel exacerbated noise-induced hearing loss. Such hearing loss...project was to develop a multi-scale model, together with relevant supporting experimental data, to describe jet fuel exacerbated NIHL. Herein we

Severe scrub typhus infection: Clinical features, diagnostic challenges and management

PubMed Central

Peter, John Victor; Sudarsan, Thomas I; Prakash, John Anthony J; Varghese, George M

2015-01-01

Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay (IFA) for the detection of IgM antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%. PMID:26261776

The Evaluation of Relationship between Sexual Self-concept and Sexual Dysfunction in Individuals Undergoing Methadone Maintenance Treatment

PubMed Central

Rajabizadeh, Ghodratolah; Yazdanpanah, Fatemeh; Ramezani, Mohammad Arash

2017-01-01

Background The present study was conducted with the aim of designing a causal model for the evaluation of sexual dysfunctions based on the variables of methadone dosage and sexual self-concept among individuals undergoing methadone maintenance treatment (MMT). Methods The study population of the present study consisted of married men of 20 to 45 years of age with sexual ýrelations and undergoing MMT for a minimum of 8 weeks referring to all MMT clinics of Kerman, Iran, in ýý2015-2016. ýThe subjects were selected through multi-stage cluster sampling (n = 250). Data were collected using the General Health Questionnaire (GHQ-28), Multi-Dimensional Sexual Self-concept Questionnaire (MSSQ), and Internal Index for Erectile Function (IIEF). Data were analyzed using path analysis method and Pearson correlation coefficient. The suggested model was evaluated using structural equation model (SEM), and indirect relationships were assessed using Bootstrap method. Findings The suggested model showed acceptable fitness with the data, and all routes, except methadone use route, to sexual function were significant. The result of the multiple ýindirect route showed that sexual function had a significant relationship with methadone use through ýsexual self-concept. In total, 60% of variance in sexual dysfunction was explained using the variables of the suggested model. Conclusion Further studies are suggested to be conducted regarding psychological factors effective on the sexual dysfunctions among individuals undergoing MMT, such as sexual self-concept. Moreover, more detailed evaluation of each subscale of positive and negative sexual self-concept is recommended to assess the psychological causes of sexual dysfunctions in these individuals and design psychological, behavioral, and cognitive-behavioral treatment interventions for them. PMID:29299211

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

PubMed

Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.

The Evaluation of Relationship between Sexual Self-concept and Sexual Dysfunction in Individuals Undergoing Methadone Maintenance Treatment.

PubMed

Rajabizadeh, Ghodratolah; Yazdanpanah, Fatemeh; Ramezani, Mohammad Arash

2017-04-01

The present study was conducted with the aim of designing a causal model for the evaluation of sexual dysfunctions based on the variables of methadone dosage and sexual self-concept among individuals undergoing methadone maintenance treatment (MMT). The study population of the present study consisted of married men of 20 to 45 years of age with sexual ýrelations and undergoing MMT for a minimum of 8 weeks referring to all MMT clinics of Kerman, Iran, in ýý2015-2016. ýThe subjects were selected through multi-stage cluster sampling (n = 250). Data were collected using the General Health Questionnaire (GHQ-28), Multi-Dimensional Sexual Self-concept Questionnaire (MSSQ), and Internal Index for Erectile Function (IIEF). Data were analyzed using path analysis method and Pearson correlation coefficient. The suggested model was evaluated using structural equation model (SEM), and indirect relationships were assessed using Bootstrap method. The suggested model showed acceptable fitness with the data, and all routes, except methadone use route, to sexual function were significant. The result of the multiple ýindirect route showed that sexual function had a significant relationship with methadone use through ýsexual self-concept. In total, 60% of variance in sexual dysfunction was explained using the variables of the suggested model. Further studies are suggested to be conducted regarding psychological factors effective on the sexual dysfunctions among individuals undergoing MMT, such as sexual self-concept. Moreover, more detailed evaluation of each subscale of positive and negative sexual self-concept is recommended to assess the psychological causes of sexual dysfunctions in these individuals and design psychological, behavioral, and cognitive-behavioral treatment interventions for them.

The roles and potential therapeutic implications of CXCL4 and its variant CXCL4L1 in the pathogenesis of chronic liver allograft dysfunction.

PubMed

Li, Jing; Liu, Bin; Yan, Lu-nan; Lau, Wan-yee

2015-02-01

Chronic liver allograft dysfunction is the leading cause of patient morbidity and late allograft loss after liver transplantation. The pathogenesis of chronic liver allograft dysfunction remains unknown. Recent studies have demonstrated that CXCL4 and its variant CXCL4L1 are involved in organ damage induced through inflammatory and immune responses throughout all stages of liver transplantation. CXCL4 and CXCL4L1 are low-molecular-weight proteins that have been implicated in hematopoiesis, angiostasis, organ fibrogenesis, mitogenesis, tumor growth and metastasis. The purpose of this review is to discuss the current status and future developments of research into the roles of CXCL4 and CXCL4L1 in the pathogenesis of chronic liver allograft dysfunction. The potential utilization of CXCL4 and CXCL4L1 as therapeutic targets for chronic liver allograft dysfunction will also be discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

PubMed Central

Ten, Vadim S.

2017-01-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units—alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise. PMID:27901512

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.

PubMed

Ten, Vadim S

2017-02-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

PubMed Central

2013-01-01

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient’s mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer’s drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction. PMID:24156319

[Epithelial dysfunction associated with pyo-inflammatory diseases of the ENT organs].

PubMed

Petukhova, N A

The modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome associated with pyo-inflammatory ENT diseases is presented. It has provided a basis for the analysis of the initial stages of etiopathogenesis of acute and chronic inflammation in the ENT system including the mucous and associated lymphoid tissues as well as the Pirogov-Waldeyer limphopharyngeal ring making up the first protective barrier. The leading role of dysbiosis of synanthropic microflora and endotoxins of the Gram-negative bacteria in the mechanisms of regional responsiveness of the organism to the infection and chronic endotoxic aggression is demonstrated. The regional and synthetic mechanisms underlying the interaction between the external and internal media of the organism are subjected to the analysis with special reference to those operating in epithelium. The possible variants of the outcome of these processes are considered including both the recovery and the development of chronic inflammation. It has been proved that the exhaustion of the internal reserves for the stabilization of the epithelium-associated lymphoid tissue system including the Pirogov-Waldeyer limphopharyngeal ring leads to the formation of epithelial dysfunction as the initial stage of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome. It is concluded that the modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome is a fundamental interdisciplinary phenomenon.

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

PubMed

Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

2018-05-01

Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

PubMed

Pinato, D J; Sharma, R; Citti, C; Platt, H; Ventura-Cots, M; Allara, E; Chen, T-Y; Dalla Pria, A; Jain, M; Mínguez, B; Kikuchi, L; Kaufman West, E; Merli, M; Kaplan, D E; Hasson, H; Marks, K; Nelson, M; Núñez, M; Aytaman, A; Bower, M; Bräu, N

2018-01-01

Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm 3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC. © 2017 John Wiley & Sons Ltd.

Decreased Autophagy Contributes to Myocardial Dysfunction in Rats Subjected to Nonlethal Mechanical Trauma

PubMed Central

Liang, Feng; Li, Xiaoyu; Wang, Li; Yang, Caihong; Yan, Zi; Zhang, Suli; Liu, Huirong

2013-01-01

Autophagy is important in cells for removing damaged organelles, such as mitochondria. Insufficient autophagy plays a critical role in tissue injury and organ dysfunction under a variety of pathological conditions. However, the role of autophagy in nonlethal traumatic cardiac damage remains unclear. The aims of the present study were to investigate whether nonlethal mechanical trauma may result in the change of cardiomyocyte autophagy, and if so, to determine whether the changed myocardial autophagy may contribute to delayed cardiac dysfunction. Male adult rats were subjected to nonlethal traumatic injury, and cardiomyocyte autophagy, cardiac mitochondrial function, and cardiac function in isolated perfused hearts were detected. Direct mechanical traumatic injury was not observed in the heart within 24 h after trauma. However, cardiomyocyte autophagy gradually decreased and reached a minimal level 6 h after trauma. Cardiac mitochondrial dysfunction was observed by cardiac radionuclide imaging 6 h after trauma, and cardiac dysfunction was observed 24 h after trauma in the isolated perfused heart. These were reversed when autophagy was induced by administration of the autophagy inducer rapamycin 30 min before trauma. Our present study demonstrated for the first time that nonlethal traumatic injury caused decreased autophagy, and decreased autophagy may contribute to post-traumatic organ dysfunction. Though our study has some limitations, it strongly suggests that cardiac damage induced by nonlethal mechanical trauma can be detected by noninvasive radionuclide imaging, and induction of autophagy may be a novel strategy for reducing posttrauma multiple organ failure. PMID:23977036

Cardiovascular and systemic effects of gastric dilatation and volvulus in dogs.

PubMed

Sharp, Claire R; Rozanski, Elizabeth A

2014-09-01

Gastric dilatation and volvulus (GDV) is a common emergency condition in large and giant breed dogs that is associated with high morbidity and mortality. Dogs with GDV classically fulfill the criteria for the systemic inflammatory response syndrome (SIRS) and can go on to develop multiple organ dysfunction syndrome (MODS). Previously reported organ dysfunctions in dogs with GDV include cardiovascular, respiratory, gastrointestinal, coagulation and renal dysfunction. Cardiovascular manifestations of GDV include shock, cardiac arrhythmias and myocardial dysfunction. Respiratory dysfunction is also multifactorial, with contributory factors including decreased respiratory excursion due to gastric dilatation, decreased pulmonary perfusion and aspiration pneumonia. Gastrointestinal dysfunction includes gastric necrosis and post-operative gastrointestinal upset such as regurgitation, vomiting, and ileus. Coagulation dysfunction is another common feature of MODS in dogs with GDV. Disseminated intravascular coagulation can occur, putting them at risk of complications associated with thrombosis in the early hypercoagulable state and hemorrhage in the subsequent hypocoagulable state. Acute kidney injury, acid-base and electrolyte disturbances are also reported in dogs with GDV. Understanding the potential for systemic effects of GDV allows the clinician to monitor patients astutely and detect such complications early, facilitating early intervention to maximize the chance of successful management. Copyright © 2014 Elsevier Inc. All rights reserved.

A 46-Year-Old Woman With Dyspnea From an Inhalational Exposure, Triggering Thyroid Storm and Subsequent Multi-Organ System Failure.

PubMed

Moraco, Andrew H; Banauch, Gisela; Kopec, Scott

2015-12-01

Thyroid storm is a rare, life-threatening condition which arises in patients with thyrotoxicosis, with an annual incidence of 2 patients per 1,000,000 and a mortality rate of 11%. We present the case of a 46-year-old-female with a medical history of controlled mild intermittent asthma, who presented with a severe asthma exacerbation, that triggered thyroid storm after exposure to polyurethane fumes. This patient represents, to the best of our knowledge, the first patient in whom the stress related to a severe asthma attack triggered the development of thyroid storm. She also is the first patient with no indication of cardiac dysfunction who developed fatal cardiac arrest after initiation of b-blockade for treatment of thyroid storm. © The Author(s) 2015.

Bridge to transplantation with a left ventricular assist device.

PubMed

Jung, Jae Jun; Sung, Kiick; Jeong, Dong Seop; Kim, Wook Sung; Lee, Young Tak; Park, Pyo Won

2012-04-01

A 61-year-old female patient was diagnosed with dilated cardiomyopathy with severe left ventricle dysfunction. Two days after admission, continuous renal replacement therapy was performed due to oliguria and lactic acidosis. On the fifth day, an intra-aortic balloon pump was inserted due to low cardiac output syndrome. Beginning 4 days after admission, she was supported for 15 days thereafter with an extracorporeal left ventricular assist device (LVAD) because of heart failure with multi-organ failure. A heart transplant was performed while the patient was stabilized with the LVAD. She developed several complications after the surgery, such as cytomegalovirus pneumonia, pulmonary tuberculosis, wound dehiscence, and H1N1 infection. On postoperative day 19, she was discharged from the hospital with close follow-up and treatment for infection. She received follow-up care for 10 months without any immune rejection reaction.

Causes, effects and connectivity changes in MS-related cognitive decline.

PubMed

Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik

2016-01-01

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

AMP-Activated Protein Kinase Deficiency Rescues Paraquat-Induced Cardiac Contractile Dysfunction Through an Autophagy-Dependent Mechanism

PubMed Central

Wang, Qiurong; Yang, Lifang; Hua, Yinan; Nair, Sreejayan; Xu, Xihui; Ren, Jun

2014-01-01

Aim: Paraquat, a quaternary nitrogen herbicide, is a highly toxic prooxidant resulting in multi-organ failure including the heart although the underlying mechanism still remains elusive. This study was designed to examine the role of the cellular fuel sensor AMP-activated protein kinase (AMPK) in paraquat-induced cardiac contractile and mitochondrial injury. Results: Wild-type and transgenic mice with overexpression of a mutant AMPK α2 subunit (kinase dead, KD), with reduced activity in both α1 and α2 subunits, were administered with paraquat (45 mg/kg) for 48 h. Paraquat elicited cardiac mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic diameter and reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca2+ handling, reduced cell survival, and overt mitochondrial damage (loss in mitochondrial membrane potential). In addition, paraquat treatment promoted phosphorylation of AMPK and autophagy. Interestingly, deficiency in AMPK attenuated paraquat-induced cardiac contractile and intracellular Ca2+ derangement. The beneficial effect of AMPK inhibition was associated with inhibition of the AMPK-TSC-mTOR-ULK1 signaling cascade. In vitro study revealed that inhibitors for AMPK and autophagy attenuated paraquat-induced cardiomyocyte contractile dysfunction. Conclusion: Taken together, our findings revealed that AMPK may mediate paraquat-induced myocardial anomalies possibly by regulating the AMPK/mTOR-dependent autophagy. PMID:25092649

Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation.

PubMed

Corbacioglu, Selim; Richardson, Paul G

2017-10-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile. In children and adults following HSCT, defibrotide is approved for the treatment of hepatic VOD/SOS with concomitant renal or pulmonary dysfunction in the United States and for the treatment of severe hepatic VOD/SOS in the European Union. Day +100 survival rates with defibrotide are superior to those of historical controls receiving best supportive care only, and safety profiles are similar. Expert commentary: Defibrotide appears to act through multiple mechanisms to restore thrombo-fibrinolytic balance and protect endothelial cells, and there are promising data on the use of defibrotide for VOD/SOS prophylaxis in high-risk children undergoing HSCT. An ongoing randomized controlled trial in children and adults will better assess the clinical value of defibrotide as a preventive medication.

Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment

PubMed Central

Yu, Jun-Feng; Feng, Yan-Yan

2017-01-01

Trichloroethylene (TCE) is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD) with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT) and scored the inflammation on the guinea pigs’ skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment. PMID:28867961

Maternal mortality and derivations from the WHO near-miss tool: An institutional experience over a decade in Southern India.

PubMed

Halder, Ajay; Jose, Ruby; Vijayselvi, Reeta

2014-01-01

Preceding the use of World Health Organization (WHO) near-miss approach in our institute for the surveillance of Severe Maternal Outcome (SMO), we pilot-tested the tool on maternal death cases that took place over the last 10 years in order to establish its feasibility and usefulness at the institutional level. This was a retrospective review of maternal deaths in Christian Medical College Vellore, India, over a decade. Cases were recorded and analyzed using the WHO near-miss tool. The International Classification of Diseases, 10(th) Revision was used to define and classify maternal mortality. There were 98,139 total births and 212 recorded maternal deaths. Direct causes of mortality constituted 46.96% of total maternal deaths, indirect causes constituted 51.40%, and unknown cases constituted 1.9%. Nonobstetrical cause (48.11%) is the single largest group. Infections (19.8%) other than puerperal sepsis remain an important group, with pulmonary tuberculosis, scrub typhus, and malaria being the leading ones. According to the WHO near-miss criteria, cardiovascular and respiratory dysfunctions are the most frequent organ dysfunctions. Incidence of coagulation dysfunction is seen highest in obstetrical hemorrhage (64%). All women who died had at least one organ dysfunction; 90.54% mothers had two- and 38.52% had four- or more organ involvement. The screening questions of the WHO near-miss tool are particularly instrumental in obtaining a comprehensive assessment of the problem beyond the International Classification of Diseases-Maternal Mortality and establish the need for laboratory-based identification of organ dysfunctions and prompt availability of critical care facilities. The process indicators, on the other hand, inquire about the basic interventions that are more or less widely practiced and therefore give no added information at the institutional level.

A Nonerythropoietic Peptide that Mimics the 3D Structure of Erythropoietin Reduces Organ Injury/Dysfunction and Inflammation in Experimental Hemorrhagic Shock

PubMed Central

Patel, Nimesh SA; Nandra, Kiran K; Brines, Michael; Collino, Massimo; Wong, WS Fred; Kapoor, Amar; Benetti, Elisa; Goh, Fera Y; Fantozzi, Roberto; Cerami, Anthony; Thiemermann, Christoph

2011-01-01

Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect—an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/ dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (NF)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB. PMID:21607291

Regulation of Mitochondrial Function and Glutamatergic System Are the Target of Guanosine Effect in Traumatic Brain Injury.

PubMed

Dobrachinski, Fernando; da Rosa Gerbatin, Rogério; Sartori, Gláubia; Ferreira Marques, Naiani; Zemolin, Ana Paula; Almeida Silva, Luiz Fernando; Franco, Jeferson Luis; Freire Royes, Luiz Fernando; Rechia Fighera, Michele; Antunes Soares, Félix Alexandre

2017-04-01

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Experimental trauma involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Mitochondrial dysfunction and glutamatergic excitotoxicity are the hallmark mechanisms of damage. Accordingly, a successful pharmacological intervention requires a multi-faceted approach. Guanosine (GUO) is known for its neuromodulator effects in various models of brain pathology, specifically those that involve the glutamatergic system. The aim of the study was to investigate the GUO effects against mitochondrial damage in hippocampus and cortex of rats subjected to TBI, as well as the relationship of this effect with the glutamatergic system. Adult male Wistar rats were subjected to a unilateral moderate fluid percussion brain injury (FPI) and treated 15 min later with GUO (7.5 mg/kg) or vehicle (saline 0.9%). Analyses were performed in hippocampus and cortex 3 h post-trauma and revealed significant mitochondrial dysfunction, characterized by a disrupted membrane potential, unbalanced redox system, decreased mitochondrial viability, and complex I inhibition. Further, disruption of Ca 2+ homeostasis and increased mitochondrial swelling was also noted. Our results showed that mitochondrial dysfunction contributed to decreased glutamate uptake and levels of glial glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter), which leads to excitotoxicity. GUO treatment ameliorated mitochondrial damage and glutamatergic dyshomeostasis. Thus, GUO might provide a new efficacious strategy for the treatment acute physiological alterations secondary to TBI.

Intestinal ischemia-reperfusion suppresses biliary excretion of hepatic organic anion transporting polypeptides substrate.

PubMed

Maruyama, Hajime; Ogura, Jiro; Fujikawa, Asuka; Terada, Yusuke; Tsujimoto, Takashi; Koizumi, Takahiro; Kuwayama, Kaori; Kobayashi, Masaki; Yamaguchi, Hiroaki; Iseki, Ken

2013-01-01

Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC₀₋₉₀) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CL(tot)) and the biliary clearance (CL(bile)) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.

Association of low non-invasive near-infrared spectroscopic measurements during initial trauma resuscitation with future development of multiple organ dysfunction.

PubMed

Nicks, Bret A; Campons, Kevin M; Bozeman, William P

2015-01-01

Near-infrared spectroscopy (NIRS) non-invasively monitors muscle tissue oxygen saturation (StO2). It may provide a continuous noninvasive measurement to identify occult hypoperfusion, guide resuscitation, and predict the development of multiple organ dysfunction (MOD) after severe trauma. We evaluated the correlation between initial StO2 and the development of MOD in multi-trauma patients. Patients presenting to our urban, academic, Level I Trauma Center/Emergency Department and meeting standardized trauma-team activation criteria were enrolled in this prospective trial. NIRS monitoring was initiated immediately on arrival with collection of StO2 at the thenar eminence and continued up to 24 hours for those admitted to the Trauma Intensive Care Unit (TICU). Standardized resuscitation laboratory measures and clinical evaluation tools were collected. The primary outcome was the association between initial StO2 and the development of MOD within the first 24 hours based on a MOD score of 6 or greater. Descriptive statistical analyses were performed; numeric means, multivariate regression and rank sum comparisons were utilized. Clinicians were blinded from the StO2 values. Over a 14 month period, 78 patients were enrolled. Mean age was 40.9 years (SD 18.2), 84.4% were male, 76.9% had a blunt trauma mechanism and mean injury severity score (ISS) was 18.5 (SD 12.9). Of the 78 patients, 26 (33.3%) developed MOD within the first 24 hours. The MOD patients had mean initial StO2 values of 53.3 (SD 10.3), significantly lower than those of non-MOD patients 61.1 (SD 10.0); P=0.002. The mean ISS among MOD patients was 29.9 (SD 11.5), significantly higher than that of non-MODS patients, 12.1 (SD 9.1) (P<0.0001). The mean shock index (SI) among MOD patients was 0.92 (SD 0.28), also significantly higher than that of non-MODS patients, 0.73 (SD 0.19) (P=0.0007). Lactate values were not significantly different between groups. Non-invasive, continuous StO2 near-infrared spectroscopy values during initial trauma resuscitation correlate with the later development of multiple organ dysfunction in this patient population.

Pediatric severe sepsis: current trends and outcomes from the Pediatric Health Information Systems database.

PubMed

Ruth, Amanda; McCracken, Courtney E; Fortenberry, James D; Hall, Matthew; Simon, Harold K; Hebbar, Kiran B

2014-11-01

To 1) describe the characteristics and outcomes over time of PICU patients with severe sepsis within the dedicated U.S. children's hospitals, 2) identify patient subgroups at risk for mortality from pediatric severe sepsis, and 3) describe overall pediatric severe sepsis resource utilization. Retrospective review of a prospectively collected multi-institutional children's hospital database. PICUs in 43 U.S. children's hospitals. PICU patients from birth to younger than 19 years were identified with severe sepsis by modified Angus criteria and International Classification of Diseases, 9th Revision, codes for severe sepsis and septic shock. None. Data from the Pediatric Health Information System database collected by the Children's Hospital Association from 2004 to 2012. Pediatric severe sepsis was defined by 1) International Classification of Diseases, 9th Revision, codes reflecting severe sepsis and septic shock and 2) International Classification of Diseases, 9th Revision, codes of infection and organ dysfunction as defined by modified Angus criteria. From 2004 to 2012, 636,842 patients were identified from 43 hospitals. Pediatric severe sepsis prevalence was 7.7% (49,153) with an associated mortality rate of 14.4%. Age less than 1 year (vs age 10 to < 19) (odds ratio, 1.4), underlying cardiovascular condition (odds ratio, 1.4) and multiple organ dysfunction, conferred higher odds of mortality. Resource burden was significant with median hospital length of stay of 17 days (interquartile range, 8-36 d) and PICU length of stay of 7 days (interquartile range, 2-17 d), with median cost/day of $4,516 and median total hospitalization cost of $77,446. There was a significant increase in the severe sepsis prevalence rate from 6.2% to 7.7% from 2004 to 2012 (p < 0.001) and a significant decrease in mortality from 18.9% to 12.0% (p < 0.001). Center mortality was negatively correlated with prevalence (rs = -0.48) and volume (rs = -0.39) and positively correlated with cost (rs = 0.36). In this largest reported pediatric severe sepsis cohort to date, prevalence increased from 2004 to 2012 while associated mortality decreased. Age, cardiovascular comorbidity, and organ dysfunction were significant prognostic factors. Pediatric severe sepsis remains an important cause for PICU admission and mortality and leads to a substantial burden in healthcare costs. Individual center's prevalence and volume are associated with improved outcomes.

The association between body mass index and severe biliary infections: a multivariate analysis.

PubMed

Stewart, Lygia; Griffiss, J McLeod; Jarvis, Gary A; Way, Lawrence W

2012-11-01

Obesity has been associated with worse infectious disease outcomes. It is a risk factor for cholesterol gallstones, but little is known about associations between body mass index (BMI) and biliary infections. We studied this using factors associated with biliary infections. A total of 427 patients with gallstones were studied. Gallstones, bile, and blood (as applicable) were cultured. Illness severity was classified as follows: none (no infection or inflammation), systemic inflammatory response syndrome (fever, leukocytosis), severe (abscess, cholangitis, empyema), or multi-organ dysfunction syndrome (bacteremia, hypotension, organ failure). Associations between BMI and biliary bacteria, bacteremia, gallstone type, and illness severity were examined using bivariate and multivariate analysis. BMI inversely correlated with pigment stones, biliary bacteria, bacteremia, and increased illness severity on bivariate and multivariate analysis. Obesity correlated with less severe biliary infections. BMI inversely correlated with pigment stones and biliary bacteria; multivariate analysis showed an independent correlation between lower BMI and illness severity. Most patients with severe biliary infections had a normal BMI, suggesting that obesity may be protective in biliary infections. This study examined the correlation between BMI and biliary infection severity. Published by Elsevier Inc.

Solid organ transplantation following end-organ failure in recipients of hematopoietic stem cell transplantation in children.

PubMed

Upadhyay, Kiran; Fine, Richard N

2014-08-01

Hematopoietic stem cell transplantation (HSCT) is an accepted treatment modality for various malignant and non-malignant disorders of the lympho-hematopoietic system. Patient survival rate has increased significantly with the use of this procedure. However, with the increase in disease-free patient survival rates, complications including various organ toxicities are also common. Kidney, liver, lung, heart, and skin are among those solid organs that are commonly affected and frequently lead to organ dysfunction and eventually end-organ disease. Conservative measures may or may not be successful in managing the organ failure in these patients. Solid organ transplantation has been shown to be promising in those patients who fail conservative management. This review will summarize the causes of solid organ (kidney, liver, and lung) dysfunction and the available data on transplantation of these solid organs in post-HSCT recipients.

The Dysfunctions of Bureaucratic Structure.

ERIC Educational Resources Information Center

Duttweiler, Patricia Cloud

1988-01-01

Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…

[Channels: a new way to revisit pathology].

PubMed

Fournier, Emmanuel

2014-02-01

Many "essential" diseases that manifest themselves in the form of crises or fits (epilepsies, episodic ataxia, periodic paralyses, myotonia, heart rhythm disorders, etc.) are due to ionic channel dysfunction and are thus referred to as "channelopathies". Some of these disorders are congenital, due to mutations of genes encoding channel subunits, while others result from toxic, immune or hormonal disturbances affecting channelfunction. Channelopathies take on a wide variety of clinical forms, depending on the type of channel (sodium, potassium, calcium, chloride...) and the type of dysfunction (loss or gain of function). Some apparently unrelated diseases affecting distinct organs are due to a similar dysfunction of the same channel, revealing unsuspected relationships between organs and between medical specialties. In addition, a given syndrome can be caused by distinct channel dysfunctions. This provides new opportunities for diferential diagnosis and specific correction of the causal defects, although some treatments find applications across multiple medical specialties.

The perils of dimensionalization: challenges in distinguishing negative traits from personality disorders.

PubMed

Wakefield, Jerome C

2008-09-01

The harmful dysfunction analysis of mental disorder is used to assess whether traits are indicative of personality disorder, and the ways such an inference can go wrong. Personality is an overall organization that allows the organism to accomplish basic goals within the constraints of its basic traits and specific intentional states. Extreme traits can be negative or "dysfunctional" in the sense that they interfere with the achievement of socially or personally valued goals; however, they are not necessarily dysfunctions or disorders in the biological or medical sense. Thus, no sheer assessment of a set of traits can offer sufficient information for a diagnosis of personality disorder. Nor do criteria such as maladaptiveness, impairment, or clinical significance necessarily transform a trait into a personality disorder. The DSM's most plausible suggestion for judging when traits are dysfunctions, inflexibility, is also problematic because many nondisordered traits are inflexible as well.

Oral disease profiles in chronic graft versus host disease.

PubMed

Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z

2015-04-01

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. © International & American Associations for Dental Research 2015.

Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis

PubMed Central

Mayr, Florian B.; Yende, Sachin; Linde-Zwirble, Walter T.; Peck-Palmer, Octavia M.; Barnato, Amber E.; Weissfeld, Lisa A.; Angus, Derek C.

2013-01-01

Context Severe sepsis, defined as infection complicated by acute organ dysfunction, occurs more frequently and leads to more deaths in black than in white individuals. The optimal approach to minimize these disparities is unclear. Objective To determine the extent to which higher severe sepsis rates in black than in white patients are due to higher infection rates or to a higher risk of acute organ dysfunction. Design, Setting, and Participants Analysis of infection-related hospitalizations from the 2005 hospital discharge data of 7 US states and infection-related emergency department visits from the 2003-2007 National Hospital Ambulatory Care Survey. Main Outcome Measure Age- and sex-standardized severe sepsis and infection hospitalization rates and the risk of acute organ dysfunction. Results Of 8 661 227 non–childbirth-related discharges, 2 261 857 were associated with an infection, and of these, 381 787 (16.8%) had severe sepsis. Black patients had a 67% higher age- and sex-standardized severe sepsis rate than did white patients (9.4; 95% confidence interval [CI], 9.3-9.5 vs 5.6; 95% CI, 5.6-5.6 per 1000 population; P<.001) and 80% higher standardized mortality (1.8, 95% CI, 1.8-1.9 vs 1.0, 95% CI, 1.0-1.1 per 1000 population; P<.001). The higher severe sepsis rate was explained by both a higher infection rate in black patients (47.3; 95% CI, 47.1-47.4 vs 34.0; 95% CI, 33.9-34.0 per 1000 population; incidence rate ratio, 1.39; P<.001) and a higher risk of developing acute organ dysfunction (age- and sex-adjusted odds ratio [OR],1.29; 95% CI, 1.27-1.30; P<.001). Differences in infection presented broadly across different sites and etiology of infection and for community- and hospital-acquired infections and occurred despite a lower likelihood of being admitted for infection from the emergency department (adjusted OR, 0.70; 95% CI, 0.64-0.76; P<.001). The higher risk of organ dysfunction persisted but was attenuated after adjusting for age, sex, comorbid conditions, poverty, and hospital effect (OR, 1.14; 95% CI, 1.13-1.16; P<.001). Racial disparities in infection and severe sepsis incidence and mortality rates were largest among younger adults (eg, the proportion of invasive pneumococcal disease occurring in adults <65 years was 73.9% among black patients vs 44.5% among white patients, P<.001). Conclusion Racial differences in severe sepsis are explained by both a higher infection rate and a higher risk of acute organ dysfunction in black than in white individuals. PMID:20571016

Toxic hepatitis in occupational exposure to solvents

PubMed Central

Malaguarnera, Giulia; Cataudella, Emanuela; Giordano, Maria; Nunnari, Giuseppe; Chisari, Giuseppe; Malaguarnera, Mariano

2012-01-01

The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work. PMID:22719183

Magnetic resonance imaging of pelvic floor dysfunction.

PubMed

Lalwani, Neeraj; Moshiri, Mariam; Lee, Jean H; Bhargava, Puneet; Dighe, Manjiri K

2013-11-01

Pelvic floor dysfunction is largely a complex problem of multiparous and postmenopausal women and is associated with pelvic floor or organ descent. Physical examination can underestimate the extent of the dysfunction and misdiagnose the disorders. Functional magnetic resonance (MR) imaging is emerging as a promising tool to evaluate the dynamics of the pelvic floor and use for surgical triage and operative planning. This article reviews the anatomy and pathology of pelvic floor dysfunction, typical imaging findings, and the current role of functional MR imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

Hepatic dysfunction.

PubMed

McCord, Kelly W; Webb, Craig B

2011-07-01

This article reviews the common pathophysiology that constitutes hepatic dysfunction, regardless of the inciting cause. The systemic consequences of liver failure and the impact of this condition on other organ systems are highlighted. The diagnostic tests available for determining the cause and extent of liver dysfunction are outlined, treatment strategies aimed at supporting hepatic health and recovery are discussed, and prognosis is briefly covered. The article emphasizes the fact that because of the central role of the liver in maintaining normal systemic homeostasis, hepatic dysfunction cannot be effectively addressed as an isolated entity. Copyright © 2011 Elsevier Inc. All rights reserved.

TiO2 nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight.

PubMed

Chen, Qun; Wang, Ningning; Zhu, Mingjiang; Lu, Jianhong; Zhong, Huiqin; Xue, Xinli; Guo, Shuoyuan; Li, Min; Wei, Xinben; Tao, Yongzhen; Yin, Huiyong

2018-05-01

Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in food and cosmetics but the health impact of human exposure remains poorly defined. Emerging evidence suggests that TiO 2 NPs may elicit immune responses by acting on macrophages. Our proteomic study showed that treatment of macrophages with TiO 2 NPs led to significant re-organization of cell membrane and activation of inflammation. These observations were further corroborated with transmission electron microscopy (TEM) experiments, which demonstrated that TiO 2 NPs were trapped inside of multi-vesicular bodies (MVB) through endocytotic pathways. TiO 2 NP caused significant mitochondrial dysfunction by increasing levels of mitochondrial reactive oxygen species (ROS), decreasing ATP generation, and decreasing metabolic flux in tricarboxylic acid (TCA) cycle from 13 C-labelled glutamine using GC-MS-based metabolic flux analysis. Further lipidomic analysis showed that TiO 2 NPs significantly decreased levels of cardiolipins, an important class of mitochondrial phospholipids for maintaining proper function of electron transport chains. Furthermore, TiO 2 NP exposure activates inflammatory responses by increasing mRNA levels of TNF-α, iNOS, and COX-2. Consistently, our targeted metabolomic analysis showed significantly increased production of COX-2 metabolites including PGD 2 , PGE 2 , and 15d-PGJ 2 . In addition, TiO 2 NP also caused significant attenuation of phagocytotic function of macrophages. In summary, our studies utilizing multiple powerful omic techniques suggest that human exposure of TiO 2 NPs may have profound impact on macrophage function through activating inflammatory responses and causing mitochondrial dysfunction without physical presence in mitochondria. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The autodigestion hypothesis: Proteolytic receptor cleavage in rheological and cardiovascular cell dysfunction1

PubMed Central

Schmid-Schönbein, Geert W.

2017-01-01

Transformation of circulating leukocytes from a dormant into an activated state with changing rheological properties leads to a major shift of their behavior in the microcirculation. Low levels of pseudopod formation or expression of adhesion molecules facilitate relatively free passage through microvessels while activated leukocytes with pseudopods and enhanced levels of adhesion membrane proteins become trapped in microvessels, attach to the endothelium and migrate into the tissue. The transformation of leukocytes into an activated state is seen in many diseases. While mechanisms for activation due to infections, tissue trauma, as well as non-physiological biochemical or biophysical exposures are well recognized, the mechanisms for activation in many diseases have not been conclusively liked to these traditional mechanisms and remain unknown. We summarize our recent evidence suggesting a major and surprising role of digestive enzymes in the small intestine as root causes for leukocyte activation and microvascular disturbances. During normal digestion of food digestive enzymes are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. When permeability of this barrier increases, these powerful degrading enzymes leak into the wall of the intestine and into the systemic circulation. Leakage of digestive enzymes occurs for example in physiological shock and multi-organ failure. Entry of digestive enzymes into the wall of the small intestine leads to degradation of the intestinal tissue in an autodigestion process. The digestive enzymes and tissue/food fragments generate not only activate leukocytes but also cause numerous cell dysfunctions. For example, proteolytic destruction of membrane receptors, plasma proteins and other biomolecules occurs. We conclude that escape of digestive enzymes from the intestinal track serves as a major source of cell dysfunction, morbidity and even mortality, including abnormal leukocyte activation seen in rheological studies. PMID:28269737

Fundamentals of Embouchure in Brass Players: Towards a Definition and Clinical Assessment.

PubMed

Woldendorp, Kees H; Boschma, Hans; Boonstra, Anne M; Arendzen, Hans J; Reneman, Michiel F

2016-12-01

Brass players may experience problems producing an optimal sound (or range of sounds) in their instrument. Assessing and treating dysfunctional embouchure requires knowledge of functional embouchure, but peer-reviewed literature on dysfunctional and functional embouchure is scarce. This study aimed to provide a narrative overview of embouchure based on information from different scientific and clinical fields. This should be regarded as a first step in constructing a reliable, valid, and practical multi-item method to assess embouchure for brass players. Literature reviews were conducted concerning: 1) the definition of embouchure, 2) physics and acoustics of embouchure, 3) functioning of embouchure-related structures, and 4) instruments to assess embouchure. Also, embouchure experts (clinicians, scientists, and elite wind players) were consulted for information and discussion. A proposal for a new definition of embouchure, an overview of the relevant physics and acoustics, functions of embouchure-related body structures, and the main methods to measure embouchure in brass playing are presented. Peer-reviewed information about the fundamentals of dysfunctional embouchure is scarce and sometimes contradictory. A new definition for embouchure is proposed: embouchure is the process needed to adjust the amount, pressure, and direction of the air flow (generated by the breath support) as it travels through the mouth cavity and between the lips, by the position and/or movements of the tongue, teeth, jaws, cheeks, and lips, to produce a tone in a wind instrument. An integrative overview is presented which can serve as a transparent foundation for the present understanding of functional and dysfunctional embouchure and for developing an evidence-based multi-item assessment instrument.

Hemorrhage-induced hepatic injury and hypoperfusion can be prevented by direct peritoneal resuscitation.

PubMed

Hurt, Ryan T; Zakaria, El Rasheid; Matheson, Paul J; Cobb, Mahoney E; Parker, John R; Garrison, R Neal

2009-04-01

Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes). Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet-dry ratio). Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 +/- 28 microg/mL and aspartate aminotransferase (AST), 234 +/- 24 microg/mL; p < 0.05) compared to group 1 (73 +/- 9 and 119 +/- 10 microg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 +/- 9 microg/mL and AST 150 +/- 17 microg/mL), and tissue edema was similar to sham. CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function.

An analysis of the NIH-supported sickle cell disease research portfolio.

PubMed

Gavini, Nara; Hoots, W Keith; Mensah, George A; Hanspal, Manjit

2015-02-01

Sickle cell disease (SCD), an inherited blood disorder is due to a single amino acid substitution on the beta chain of hemoglobin, and is characterized by anemia, severe infections, acute and chronic pain, and multi-organ damage. The National Institutes of Health (NIH) is dedicated to support basic, translational and clinical science research to improve care and ultimately, to find a cure for SCD that causes such suffering. This report provides a detailed analysis of grants funded by the NIH for SCD research in Fiscal Years 2007 through 2013. During this period, the NIH supported 247 de novo grants totaling $272,210,367 that address various aspects of SCD. 83% of these funds supported research project grants investigating the following 5 scientific themes: Pathology of Sickle Red Blood Cells; Globin Gene Expression; Adhesion and Vascular Dysfunction; Neurological Complications and Organ-specific Dysfunction; and Pain Management and Intervention. The remaining 17% of total funds supported career development and training grants; Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants; large Center grants; and Conference grants. Further analysis showed that the National Heart, Lung, and Blood Institute (NHLBI) is the largest funder of SCD research within NIH with 67% of total grants, contributing 77% of total funds; followed by the National Institute for Digestive Diseases and Kidney (NIDDK) that is funding 19% of grants, contributing 13% of total funds. The remaining 14% of grants totaling 10% of the funds were supported by all other NIH Institutes/Centers (ICs) combined. In summary, the NIH is using multiple funding mechanisms to support a sickle cell disease research agenda that is intended to advance the detection, treatment, and cure of this debilitating genetic disease. Published by Elsevier Inc.

Tropic lightning: myth or menace?

PubMed

McCarthy, John

2014-11-01

Lightning is one of the leading causes of death related to environmental disaster. Of all lightning fatalities documented between 2006 and 2012, leisure activities contributed the largest proportion of deaths, with water-associated, sports, and camping being the most common. Despite the prevalence of these activities throughout the islands, Hawai'i has had zero documented lightning fatalities since weather data tracking was initiated in 1959. There is a common misconception that lightning does not strike the ground in Hawai'i. This myth may contribute to a potentially dangerous false sense of security, and recognition of warning signs and risk factor modification remain the most important prevention strategies. Lightning damage occurs on a spectrum, from minor burns to multi-organ dysfunction. After injury, initial treatment should focus on "reverse triage" and immediate cardiopulmonary resuscitation when indicated, followed by transfer to a healthcare facility. Definitive treatment entails monitoring and management of potential sequelae, to include cardiovascular, neurologic, dermatologic, ophthalmologic, audiovestibular, and psychiatric complications.

REQUIREMENT OF ARGININOSUCCINATE LYASE FOR SYSTEMIC NITRIC OXIDE PRODUCTION

PubMed Central

Erez, Ayelet; Nagamani, Sandesh CS.; Shchelochkov, Oleg A.; Premkumar, Muralidhar H.; Campeau, Philippe M.; Chen, Yuqing; Garg, Harsha K.; Li, Li; Mian, Asad; Bertin, Terry K.; Black, Jennifer O.; Zeng, Heng; Tang, Yaoping; Reddy, Anilkumar K.; Summar, Marshall; O’Brien, William E.; Harrison, David G.; Mitch, William E.; Marini, Juan C.; Aschner, Judy L.; Bryan, Nathan S.; Lee, Brendan

2012-01-01

Nitric Oxide (NO) plays a critical role in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (Asl) deficiency exhibits a distinct phenotype manifest by multi-organ dysfunction and NO deficiency. Loss of Asl leads to reduced NO synthesis due to decreased endogenous arginine synthesis as well as reduced utilization of extracellular arginine for NO production in both humans and mice. Hence, ASL as seen in other species through evolution has a structural function in addition to its catalytic activity. Importantly, therapy with nitrite rescued the tissue autonomous NO deficiency in hypomorphic Asl mice, while a NOS independent NO donor restored NO-dependent vascular reactivity in subjects with ASL deficiency. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as treatment of NO-related diseases. PMID:22081021

Transfusion-Related Acute Lung Injury (TRALI) and Transfusion-Associated Circulatory Overload (TACO) in Liver Transplantation: A Case Report and Focused Review.

PubMed

Smith, Natalie K; Kim, Sang; Hill, Bryan; Goldberg, Andrew; DeMaria, Samuel; Zerillo, Jeron

2018-06-01

Liver transplantation (LT) is a complex procedure in a patient with multi-organ system dysfunction and coagulation defects. The surgical procedure involves dissection, major vessel manipulation, and pathophysiologic effects of graft storage and reperfusion. As a result, LT frequently involves significant hemorrhage. Subsequent massive transfusion carries high risk of transfusion-associated complications. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion associated mortality. In this case report and focused review, we present data that suggest that patients undergoing liver transplantation may be at higher risk for TRALI and TACO than the general population. Anesthesiologists can play a role in decreasing these risks by increasing recognition and reporting of TRALI and TACO, using point of care testing with thromboelastography to guide and decrease transfusion, and considering alternatives to traditional blood products like solvent/detergent plasma.

A case of an unexplained eosinophilic myocarditis in a dog.

PubMed

Keeshen, T P; Chalkley, M; Stauthammer, C

2016-09-01

An 8-year-old spayed female Munsterlander was evaluated for a chronic low grade fever and a two month history of exercise intolerance. On physical examination, tachycardia and a grade II/VI right systolic heart murmur were detected. Echocardiography revealed marked thickening of the atrial and ventricular walls with mixed echogenicity and concentric hypertrophy of the left and right ventricles and equivocal systolic dysfunction. Serum cardiac troponin I level was markedly elevated. Endomyocardial biopsy was attempted; however, the patient arrested during the procedure and resuscitation was unsuccessful. Post-mortem examination revealed severe, chronic atrial and ventricular eosinophilic myocarditis associated with marked interstitial fibrosis. Serological testing, histopathology and immunohistochemistry staining did not reveal an underlying infectious agent or neoplasm. To our knowledge, this is the first reported case of primary eosinophilic myocarditis in the absence of a peripheral eosinophilia and multi-organ eosinophilic inflammation in a dog. Published by Elsevier B.V.

Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach

PubMed Central

Broessner, Gregor; Beer, Ronny; Franz, Gerhard; Lackner, Peter; Engelhardt, Klaus; Brenneis, Christian; Pfausler, Bettina; Schmutzhard, Erich

2005-01-01

Introduction We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. Methods A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Results Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. Conclusion In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result. PMID:16285034

Multi-Modal Hallucinations and Cognitive Function in Parkinson's Disease

PubMed Central

Katzen, Heather; Myerson, Connie; Papapetropoulos, Spiridon; Nahab, Fatta; Gallo, Bruno; Levin, Bonnie

2010-01-01

Background/Aims Hallucinations have been linked to a constellation of cognitive deficits in Parkinson's disease (PD), but it is not known whether multi-modal hallucinations are associated with greater neuropsychological dysfunction. Methods 152 idiopathic PD patients were categorized based on the presence or absence of hallucinations and then were further subdivided into visual-only (VHonly; n = 35) or multi-modal (VHplus; n = 12) hallucination groups. All participants underwent detailed neuropsychological assessment. Results Participants with hallucinations performed more poorly on select neuropsychological measures and exhibited more mood symptoms. There were no differences between VHonly and VHplus groups. Conclusions PD patients with multi-modal hallucinations are not at greater risk for neuropsychological impairment than those with single-modal hallucinations. PMID:20689283

The Cardio-Renal Interrelationship.

PubMed

Boudoulas, Konstantinos Dean; Triposkiadis, Filippos; Parissis, John; Butler, Javed; Boudoulas, Harisios

The heart and the kidney are of utmost importance for the maintenance of cardiovascular (CV) homeostasis. In healthy subjects, hemodynamic changes in either organ may affect hemodynamics of the other organ. This interaction is fine-tuned by neurohumoral activity, including atrial natriuretic peptides, renin-angiotensin aldosterone system and sympathetic activity. Dysfunction or disease of one organ may initiate, accentuate, or precipitate dysfunction or disease state in the other organ, often leading to a vicious cycle. Further, the interaction between the heart and the kidney may occur in the setting of processes and diseases that may affect both organs simultaneously, such as advanced age, hypertension, diabetes mellitus, atherosclerosis, etc. In this regard, a stiff aorta that occurs with aging due to mechanical stress may independently initiate or precipitate dysfunction and disease in the heart and the kidney. All of these factors contribute to a high prevalence of coexistent CV and kidney disease, especially in the elderly. In advanced kidney disease, hemodynamic and neurohumoral homeostasis are lost, volume and pressure overload may coexist, and the elimination of certain pharmacologic agents may be substantially impaired. Thus, coexistence of CV and kidney disease complicates diagnosis, propagates pathophysiology, adversely affects prognosis, and hinders management. Copyright © 2016 Elsevier Inc. All rights reserved.

Donation after cardio-circulatory death liver transplantation

PubMed Central

Le Dinh, Hieu; de Roover, Arnaud; Kaba, Abdour; Lauwick, Séverine; Joris, Jean; Delwaide, Jean; Honoré, Pierre; Meurisse, Michel; Detry, Olivier

2012-01-01

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT. PMID:22969222

The alignment of immediate health effects of multi-hour exposure periods

EPA Science Inventory

Objective: Exposure to [me airborne particulate matter (PM2.5) has been associated with cardiovascular outcomes, including acute effects on endothelial dysfunction. With such immediate effects, the choice ofthe exposure timeframe may be a critical factor. This analysis compares t...

Using gene chips to identify organ-specific, smooth muscle responses to experimental diabetes: potential applications to urological diseases.

PubMed

Hipp, Jason D; Davies, Kelvin P; Tar, Moses; Valcic, Mira; Knoll, Abraham; Melman, Arnold; Christ, George J

2007-02-01

To identify early diabetes-related alterations in gene expression in bladder and erectile tissue that would provide novel diagnostic and therapeutic treatment targets to prevent, delay or ameliorate the ensuing bladder and erectile dysfunction. The RG-U34A rat GeneChip (Affymetrix Inc., Sunnyvale, CA, USA) oligonucleotide microarray (containing approximately 8799 genes) was used to evaluate gene expression in corporal and male bladder tissue excised from rats 1 week after confirmation of a diabetic state, but before demonstrable changes in organ function in vivo. A conservative analytical approach was used to detect alterations in gene expression, and gene ontology (GO) classifications were used to identify biological themes/pathways involved in the aetiology of the organ dysfunction. In all, 320 and 313 genes were differentially expressed in bladder and corporal tissue, respectively. GO analysis in bladder tissue showed prominent increases in biological pathways involved in cell proliferation, metabolism, actin cytoskeleton and myosin, as well as decreases in cell motility, and regulation of muscle contraction. GO analysis in corpora showed increases in pathways related to ion channel transport and ion channel activity, while there were decreases in collagen I and actin genes. The changes in gene expression in these initial experiments are consistent with the pathophysiological characteristics of the bladder and erectile dysfunction seen later in the diabetic disease process. Thus, the observed changes in gene expression might be harbingers or biomarkers of impending organ dysfunction, and could provide useful diagnostic and therapeutic targets for a variety of progressive urological diseases/conditions (i.e. lower urinary tract symptoms related to benign prostatic hyperplasia, erectile dysfunction, etc.).

Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus

PubMed Central

Katsuyama, Takayuki; Tsokos, George C.; Moulton, Vaishali R.

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to “self” leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites. Autoantibodies produced by B lymphocytes and immune complex deposition in vital organs contribute to tissue damage. T lymphocytes are increasingly being recognized as key contributors to disease pathogenesis. CD4 T follicular helper cells enable autoantibody production, inflammatory Th17 subsets promote inflammation, while defects in regulatory T cells lead to unchecked immune responses. A better understanding of the molecular defects including signaling events and gene regulation underlying the dysfunctional T cells in SLE is necessary to pave the path for better management, therapy, and perhaps prevention of this complex disease. In this review, we focus on the aberrations in T cell signaling in SLE and highlight therapeutic advances in this field. PMID:29868033

A comprehensive multi-institutional study of empiric therapy with flomoxef in surgical infections of the digestive organs. The Kyushu Research Group for Surgical Infection.

PubMed

Shimada, M; Takenaka, K; Sugimachi, K

1994-08-01

The effect of flomoxef as empiric therapy for surgical infections of the digestive organs was analyzed in 103 patients, most of whom (94.2%) had intra-abdominal infections. Surgical procedures were performed on 73 patients contemporaneously with the flomoxef therapy. Flomoxef is an oxacephem and has a potent and broad bactericidal spectrum against aerobes and anaerobes. It provokes fewer adverse reactions than latamoxef such as vitamin K deficiency and platelet dysfunction. Flomoxef was administered intravenously at a dose 1-4g/day for more than 3 days without any other antimicrobial agent. The clinical response was classified into 3 groups; cured, improved and failed, and both the cured and improved responses were defined as satisfactory. A satisfactory response was obtained in 99 patients (96.1%). Regarding bacteriological response, the overall eradication rate was 81.3%. Adverse reactions including abnormal laboratory data occurred in only two patients. One had abdominal pain, and the other had a mild elevation of transaminases, and both were mild and easily reversible. Therefore, flomoxef is considered to have the potential of becoming one of the most effective agents in empiric therapy for surgical infections of the digestive organs.

Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus.

PubMed

Katsuyama, Takayuki; Tsokos, George C; Moulton, Vaishali R

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to "self" leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites. Autoantibodies produced by B lymphocytes and immune complex deposition in vital organs contribute to tissue damage. T lymphocytes are increasingly being recognized as key contributors to disease pathogenesis. CD4 T follicular helper cells enable autoantibody production, inflammatory Th17 subsets promote inflammation, while defects in regulatory T cells lead to unchecked immune responses. A better understanding of the molecular defects including signaling events and gene regulation underlying the dysfunctional T cells in SLE is necessary to pave the path for better management, therapy, and perhaps prevention of this complex disease. In this review, we focus on the aberrations in T cell signaling in SLE and highlight therapeutic advances in this field.

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

PubMed

Presneill, J J; Waring, P M; Layton, J E; Maher, D W; Cebon, J; Harley, N S; Wilson, J W; Cade, J F

2000-07-01

To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Prospective cohort study. University hospital intensive care unit. A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). None. During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

Exposure to volatile organic compounds and kidney dysfunction in thin film transistor liquid crystal display (TFT-LCD) workers.

PubMed

Chang, Ta-Yuan; Huang, Kuei-Hung; Liu, Chiu-Shong; Shie, Ruei-Hao; Chao, Keh-Ping; Hsu, Wen-Hsin; Bao, Bo-Ying

2010-06-15

Many volatile organic compounds (VOCs) are emitted during the manufacturing of thin film transistor liquid crystal displays (TFT-LCDs), exposure to some of which has been reported to be associated with kidney dysfunction, but whether such an effect exists in TFT-LCD industry workers is unknown. This cross-sectional study aimed to investigate the association between exposure to VOCs and kidney dysfunction among TFT-LCD workers. The results showed that ethanol (1811.0+/-1740.4 ppb), acetone (669.0+/-561.0 ppb), isopropyl alcohol (187.0+/-205.3 ppb) and propylene glycol monomethyl ether acetate (PGMEA) (102.9+/-102.0 ppb) were the four dominant VOCs present in the workplace. The 63 array workers studied had a risk of kidney dysfunction 3.21-fold and 3.84-fold that of 61 cell workers and 18 module workers, respectively. Workers cumulatively exposed to a total level of isopropyl alcohol, PGMEA and propylene glycol monomethyl ether> or =324 ppb-year had a significantly higher risk of kidney dysfunction (adjusted OR=3.41, 95% CI=1.14-10.17) compared with those exposed to <25 ppb-year after adjustment for potential confounding factors. These findings indicated that array workers might be the group at greatest risk of kidney dysfunction within the TFT-LCD industry, and cumulative exposure to specific VOCs might be associated with kidney dysfunction. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

Endotoxemia Following Multiple Trauma: Risk Factors and Prognostic Implications.

PubMed

Charbonney, Emmanuel; Tsang, Jennifer Y; Li, Yangmei; Klein, David; Duque, Patricia; Romaschin, Alexander; Marshall, John C

2016-02-01

To evaluate the prevalence and time course of systemic endotoxemia following severe multiple trauma, to define its risk factors, and to explore the correlation between post-trauma endotoxemia and organ dysfunction. Prospective single-center cohort study. Emergency department and ICU of adult tertiary care level I trauma center. Forty-eight severely injured (Injury Severity Score ≥ 16) patients, admitted to ICU within 24 hours of injury. None. Endotoxemia was not evident on initial presentation, but developed subsequently in 75% of patients, even in the absence of Gram-negative infection. Nonsurviving patients had higher endotoxin levels than survivors on day 1 (endotoxemia, 0.48 vs 0.28; p = 0.048). Shock at admission, or surgery within the first 48 hours after trauma, was associated with higher endotoxin levels and predicted subsequent maximal endotoxemia, after adjusting for other significant covariates. Maximal endotoxemia levels were higher in patients who developed organ dysfunction, reflected in a cumulative Multiple Organ Dysfunction Score greater than 25, and patients with an intermediate endotoxemia level (≥ 0.4) had more cardiovascular dysfunction. It is the first study to detect increasing levels of endotoxemia following multiple trauma. Shock and early surgery predict the development of endotoxemia; endotoxemia is particularly associated with cardiovascular dysfunction. However, Gram-negative infections are uncommon in these patients, suggesting that the gastrointestinal tract is the dominant reservoir of endotoxin. Endotoxin may be an appropriate therapeutic target in patients who have sustained severe multiple trauma.

Cardio-renal syndromes: from foggy bottoms to sunny hills.

PubMed

Ronco, Claudio

2011-11-01

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study.

PubMed

Shah, Gaurang R; Chaudhari, Manojkumar V; Patankar, Suresh B; Pensalwar, Shrikant V; Sabale, Vilas P; Sonawane, Navneet A

2012-09-15

Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator's global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.

ITK Gene Mutation: Effect on Survival of Children with Severe Hemophagocytic Lymphohistiocytosis.

PubMed

Zheng, Fang; Li, Juan; Zha, Hui; Zhang, Jue; Zhang, Zhiquan; Cheng, Fangjun

2016-11-01

Hemophagocytic lymphohistiocytosis (HLH) is characterized by deadly hyperinflammatory syndrome, but data on severe HLH with multi-organ dysfunction in children are scant. The authors report a retrospective study of 8 cases with severe HLH from a pediatric intensive care unit (PICU) over a 1-y period and found that Epstein barr virus (EBV) -infection was the most common etiology. All patients had genetic analysis, which showed that four patients with EBV -infection had one homozygous mutation, c.985+75G>A (at position chr5:156667232) in exon10 of the ITK gene with poor survival rates. ITK + mutation group had higher percentages of CD3 + CD8 + T cells (36.0 ± 8.4 %) than those in ITK - mutation group (28.8 ± 5.5 %), while they had similar levels of CD3 + CD4 + T cells. ITK + mutation group had lower proportion of CD3 - CD19 + B cells (16.3 ± 2.9 %) and CD16 + CD56 + NK cells (8.4 ± 2.6 %) than ITK - mutation group (29.6 ± 5.1 % and 15.9 ± 9.0 % respectively). Most importantly, patients with EBV infection with c.985+75G>A mutation in ITK had lower survival rates than ITK - mutation group which it may be related with cellular immune dysfunction.

The gut in trauma.

PubMed

Patel, Jayshil J; Rosenthal, Martin D; Miller, Keith R; Martindale, Robert G

2016-08-01

The purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut-brain connection in traumatic brain injury. Newer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS). To date, therapies to mitigate acute gut dysfunction have included enteral nutrition and immunonutrition; emerging therapies aimed to intestinal mucosal layer disruption, however, include protease inhibitors such as tranexamic acid, parenteral nutrition-supplemented bombesin, and hypothermia. Clinical trials to demonstrate benefit in humans are needed before widespread applications can be recommended. Despite resuscitation, gut dysfunction promotes distant organ injury. In addition, postresuscitation nosocomial and iatrogenic 'hits' exaggerate the immune response, contributing to MODS. This was a provocative concept, suggesting infectious and noninfectious causes of inflammation may trigger, heighten, and perpetuate an inflammatory response culminating in MODS and death. Emerging evidence suggests posttraumatic injury mechanisms, such as intestinal mucosal disruption and shifting of the gut microbiome to a pathobiome. In addition, traumatic brain injury activates the gut-brain axis and increases intestinal permeability.

Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus

PubMed Central

Zhao, Jing-Bo; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr; Ejskjaer, Niels

2006-01-01

Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed. PMID:16718808

Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles.

PubMed

Guffei, Amanda; Sarkar, Rahul; Klewes, Ludger; Righolt, Christiaan; Knecht, Hans; Mai, Sabine

2010-12-01

Hodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells.1 To determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells. Three-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease. This is the first study to demonstrate nuclear remodeling and associated genomic instability leading to the generation of Reed-Sternberg cells of Hodgkin's lymphoma. We defined nuclear remodeling as a key feature of Hodgkin's lymphoma, highlighting the relevance of nuclear architecture in cancer.

An International, Multi-Specialty Validation Study of the IgG4-Related Disease Responder Index.

PubMed

Wallace, Zachary S; Khosroshahi, Arezou; Carruthers, Mollie D; Perugino, Cory A; Choi, Hyon; Campochiaro, Corrado; Culver, Emma L; Cortazar, Frank; Della-Torre, Emanuel; Ebbo, Mikael; Fernandes, Ana; Frulloni, Luca; Hart, Philip; Karadag, Omer; Kawa, Shigeyuki; Kawano, Mitsuhiro; Kim, Myung-Hwan; Lanzillotta, Marco; Matsui, Shoko; Okazaki, Kazuichi; Ryu, Jay H; Saeki, Takako; Schleinitz, Nicolas; Tanasa, Paula; Umehara, Hisanori; Webster, George; Zhang, Wen; Stone, John H

2018-02-18

IgG4-related disease (IgG4-RD) can cause fibro-inflammatory lesions in nearly any organ, leading to organ dysfunction and failure. The IgG4-RD Responder Index (RI) was developed to help investigators assess the efficacy of treatment in a structured manner. We sought to validate the RI in a multi-national investigation. The RI guides investigators through assessments of disease activity and damage in 25 domains, incorporating higher weights for disease manifestations that require treatment urgently or that worsen despite treatment. After a training exercise, investigators reviewed 12 written IgG4-RD vignettes (mean length: 279 words, range: 76-511 words) based upon real patients. Investigators calculated both an RI score as well as a physician global assessment (PGA) for each vignette. Three investigators used the RI on fifteen patients followed over serial visits after treatment. We assessed inter- and intra-rater reliability, precision, validity, and responsiveness. Twenty-six physician-investigators included representatives from 6 specialties and 9 countries. The inter-rater and intra-rater reliabilities of the RI were strong (0.88 and 0.69, respectively) and superior to those of the PGA. Correlations (construct validity) between the RI and PGA were high (Spearman's r=0.9, P<0.0001). The RI was sensitive to change (discriminant validity). Following treatment, there was significant improvement in the RI (mean change 10.5 (95% CI 5.4-12), P<0.001) which correlated with the change in the PGA. Urgent disease and damage were captured effectively. In this international, multi-specialty study, we found that the RI is a valid, and reliable disease activity assessment tool that can be used to measure response to therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Relationship between Dysfunctional Family Environments and Family Member Food Intake.

ERIC Educational Resources Information Center

Kintner, Martha; And Others

1981-01-01

Explores relationships between family environment and family food intake. Findings indicate a significant negative relationship between the family's dysfunctional environment (indicated by high conflict, control, and organization) and family dietary intake. A significant positive relationship was found between the family's cohesive and independent…

38 CFR 4.115a - Ratings of the genitourinary system-dysfunctions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Ratings of the genitourinary system—dysfunctions. Diseases of the genitourinary system generally result in... cover all symptoms resulting from genitourinary diseases, specific diagnoses may include a description... organ systems, estpecially cardiovascular 100 Persistent edema and albuminuria with BUN 40 to 80mg%; or...

Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

PubMed

Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W; Nguyen, Trung C; Reeder, Ron; Aneja, Rajesh; Shakoory, Bita; Simon, Dennis

2017-06-01

We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Tertiary children's hospital PICU. One hundred consecutive severe sepsis admissions. Clinical data were recorded daily, and blood was collected twice weekly. Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

[Application of yellow turpentine baths in patients with chronic prostatitis complicated by sexual dysfunctions].

PubMed

2005-01-01

Patients with chronic prostatitis complicated by sexual dysfunction took turpentine baths with yellow solution in concentration rising from 5 to 55 ml solution per 200 l water, temperature 35-40 degrees C, duration 5-16 min, daily, 12-15 procedures. Yellow turpentine baths raise efficacy of treatment of patients with copulative dysfunction to 64% due to intensive arterial blood inflow to the sexual organs including the cavernous bodies of the penis.

PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

PubMed Central

Girard, Beatrice M.; Tooke, Katharine; Vizzard, Margaret A.

2017-01-01

Complex organization of CNS and PNS pathways is necessary for the coordinated and reciprocal functions of the urinary bladder, urethra and urethral sphincters. Injury, inflammation, psychogenic stress or diseases that affect these nerve pathways and target organs can produce lower urinary tract (LUT) dysfunction. Numerous neuropeptide/receptor systems are expressed in the neural pathways of the LUT and non-neural components of the LUT (e.g., urothelium) also express peptides. One such neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the LUT. Mice with a genetic deletion of PACAP exhibit bladder dysfunction and altered somatic sensation. PACAP and associated receptors are expressed in the LUT and exhibit neuroplastic changes with neural injury, inflammation, and diseases of the LUT as well as psychogenic stress. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency in preclinical animal models and transgenic mouse models that mirror some clinical symptoms of bladder dysfunction. A change in the balance of the expression and resulting function of the PACAP/receptor system in CNS and PNS bladder reflex pathways may underlie LUT dysfunction including symptoms of urinary urgency, increased voiding frequency, and visceral pain. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction. PMID:29255407

The outcomes and prognostic factors of acute respiratory failure in the patients 90 years old and over.

PubMed

Chen, Wan-Ling; Chen, Chin-Ming; Kung, Shu-Chen; Wang, Ching-Min; Lai, Chih-Cheng; Chao, Chien-Ming

2018-01-23

This retrospective cohort study investigated the outcomes and prognostic factors in nonagenarians (patients 90 years old or older) with acute respiratory failure. Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring invasive mechanical ventilation (MV) were enrolled. Outcomes including in-hospital mortality and ventilator dependency were measured. A total of 173 nonagenarians with acute respiratory failure were admitted to the intensive care unit (ICU). A total of 56 patients died during the hospital stay and the rate of in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 % CI, 1.55-22.45; p = 0.009, APACHE II scores ≥ 25 vs APACHE II scores < 15), use of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; ≥ 3 organ dysfunction vs ≤ 1 organ dysfunction) were more likely to die. Among the 117 survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In conclusion, the mortality rate of nonagenarians with acute respiratory failure was high, especially for those with higher APACHE II scores or more organ dysfunction.

Influence of Obesity Diagnosis With Organ Dysfunction, Mortality, and Resource Use Among Children Hospitalized With Infection in the United States.

PubMed

Maley, Nidhi; Gebremariam, Achamyeleh; Odetola, Folafoluwa; Singer, Kanakadurga

2017-06-01

Sepsis induces inflammation in response to infection and is a major cause of mortality and hospitalization in children. Obesity induces chronic inflammation leading to many clinical manifestations. Our understanding of the impact of obesity on diseases, such as infection and sepsis, is limited. The objective of this study was to evaluate the association of obesity with organ dysfunction, mortality, duration, and charges during among US children hospitalized with infection. Retrospective study of hospitalizations in children with infection aged 0 to 20 years, using the 2009 Kids' Inpatient Database. Of 3.4 million hospitalizations, 357 701 were for infection, 5685 of which were reported as obese children. Obese patients had higher rates of organ dysfunction (7.35% vs 5.5%, P < .01), longer hospital stays (4.1 vs 3.5 days, P < .001), and accrued higher charges (US$29 019 vs US$21 200, P < .001). In multivariable analysis, mortality did not differ by obesity status (odds ratio: 0.56, 95% confidence interval: 0.23-1.34), however severity of illness modified the association between obesity status and the other outcomes. While there was no difference in in-hospital mortality by obesity diagnosis, variation in organ dysfunction, hospital stay, and hospital charges according to obesity status was mediated by illness severity. Findings from this study have significant implications for targeted approaches to mitigate the burden of obesity on infection and sepsis.

Advanced Fault Diagnosis Methods in Molecular Networks

PubMed Central

Habibi, Iman; Emamian, Effat S.; Abdi, Ali

2014-01-01

Analysis of the failure of cell signaling networks is an important topic in systems biology and has applications in target discovery and drug development. In this paper, some advanced methods for fault diagnosis in signaling networks are developed and then applied to a caspase network and an SHP2 network. The goal is to understand how, and to what extent, the dysfunction of molecules in a network contributes to the failure of the entire network. Network dysfunction (failure) is defined as failure to produce the expected outputs in response to the input signals. Vulnerability level of a molecule is defined as the probability of the network failure, when the molecule is dysfunctional. In this study, a method to calculate the vulnerability level of single molecules for different combinations of input signals is developed. Furthermore, a more complex yet biologically meaningful method for calculating the multi-fault vulnerability levels is suggested, in which two or more molecules are simultaneously dysfunctional. Finally, a method is developed for fault diagnosis of networks based on a ternary logic model, which considers three activity levels for a molecule instead of the previously published binary logic model, and provides equations for the vulnerabilities of molecules in a ternary framework. Multi-fault analysis shows that the pairs of molecules with high vulnerability typically include a highly vulnerable molecule identified by the single fault analysis. The ternary fault analysis for the caspase network shows that predictions obtained using the more complex ternary model are about the same as the predictions of the simpler binary approach. This study suggests that by increasing the number of activity levels the complexity of the model grows; however, the predictive power of the ternary model does not appear to be increased proportionally. PMID:25290670

Cerebral Dysfunctions Related to Perinatal Organic Damage: Clinical-Neuropathologic Correlations.

ERIC Educational Resources Information Center

Towbin, Abraham

1978-01-01

Recent neuropathology studies identify hypoxia as the main cause of perinatal cerebral damage. Cerebral lesions present at birth, with transition to chronic scar lesions, are correlated to mental retardation, cerebral palsy, epilepsy, and minimal brain dysfunction. Gestation age and severity of hypoxic exposure essentially determine the cerebral…

Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: Novel therapeutic implications and challenges.

PubMed

Hattori, Yuichi; Hattori, Kohshi; Suzuki, Tokiko; Matsuda, Naoyuki

2017-09-01

Sepsis is one of the most common reasons for critically ill patients to be admitted to an intensive care unit and, despite advances in overall medical care, it represents a major clinical problem and remains the leading cause of death in the critically ill patient population. Although sepsis has been defined as a systemic inflammatory syndrome, in which there is an identifiable focus of infection, clinical trials aimed at anti-inflammatory therapeutic approaches have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis. Very recently, the third international consensus definitions have been advocated for sepsis and septic shock. Thus, sepsis is now defined as life-threatening organ dysfunction due to a dysregulated host response to infection. A better understanding of the molecular mechanisms involved in the pathogenesis of sepsis and its resultant organ failure has been sought, and the development of therapies targeted at preventing or limiting molecular events associated with the progress of fatal organ failure, hence leading to improvement of outcomes, is urgently needed. This review article provides an overview of possible pathogenic mechanisms underlying the development of multiple organ dysfunction in sepsis and discusses pharmacological agents regarded as promising in treatment of this disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Smooth muscle membrane organization in the normal and dysfunctional human urinary bladder: a structural analysis.

PubMed

Burkhard, Fiona C; Monastyrskaya, Katia; Studer, Urs E; Draeger, Annette

2005-01-01

The decline in contractile properties is a characteristic feature of the dysfunctional bladder as a result of infravesical outlet obstruction. During clinical progression of the disease, smooth muscle cells undergo structural modifications. Since adaptations to constant changes in length require a high degree of structural organization within the sarcolemma, we have investigated the expression of several proteins, which are involved in smooth muscle membrane organization, in specimens derived from normal and dysfunctional organs. Specimen from patients with urodynamically normal/equivocal (n = 4), obstructed (n = 2), and acontractile (n = 2) bladders were analyzed relative to their structural features and sarcolemmal protein profile. Smooth muscle cells within the normal urinary bladder display a distinct sarcolemmal domain structure, characterized by firm actin-attachment sites, alternating with flexible "hinge" regions. In obstructed bladders, foci of cells displaying degenerative sarcolemmal changes alternate with areas of hypertrophic cells in which the membrane appears unaffected. In acontractile organs, the overall membrane structure remains intact, however annexin 6, a protein belonging to a family of Ca2+-dependent, "membrane-organizers," is downregulated. Degenerative changes in smooth muscle cells, which are chronically working against high resistance, are preferentially located within the actin-attachment sites. In acontractile bladders, the downregulation of annexin 6 might have a bearing on the fine-tuning of the plasma membrane during contraction/relaxation cycles. Copyright 2005 Wiley-Liss, Inc.

Advances in understanding the pathogenesis of HLH.

PubMed

Usmani, G Naheed; Woda, Bruce A; Newburger, Peter E

2013-06-01

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X-linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule-dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi-organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined. © 2013 John Wiley & Sons Ltd.

Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction

PubMed Central

Pokrovskiy, Mihail V.; Korokin, Mihail V.; Tsepeleva, Svetlana A.; Pokrovskaya, Tatyana G.; Gureev, Vladimir V.; Konovalova, Elena A.; Gudyrev, Oleg S.; Kochkarov, Vladimir I.; Korokina, Liliya V.; Dudina, Eleonora N.; Babko, Anna V.; Terehova, Elena G.

2011-01-01

This paper is about a way of correction of endothelial dysfunction with the inhibitor of arginase: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction. PMID:21747978

Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

PubMed

Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

2014-12-01

Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important. Copyright © 2014 Elsevier Inc. All rights reserved.

Occupation Attributes Relate to Location of Atrophy in Frontotemporal Lobar Degeneration

ERIC Educational Resources Information Center

Spreng, R. N.; Rosen, H. J.; Strother, S.; Chow, T. W.; Diehl-Schmid, J.; Freedman, M.; Graff-Radford, N. R.; Hodges, J. R.; Lipton, A. M.; Mendez, M. F.; Morelli, S. A.; Black, S. E.; Miller, B. L.; Levine, Brian

2010-01-01

Frontotemporal lobar degeneration (FTLD) often presents with asymmetric atrophy. We assessed whether premorbid occupations in FTLD patients were associated with these hemispheric asymmetries. In a multi-center chart review of 588 patients, occupation information was related to location of tissue loss or dysfunction. Patients with atrophy…

Voice Dysfunction in Dysarthria: Application of the Multi-Dimensional Voice Program.

ERIC Educational Resources Information Center

Kent, R. D.; Vorperian, H. K.; Kent, J. F.; Duffy, J. R.

2003-01-01

Part 1 of this paper recommends procedures and standards for the acoustic analysis of voice in individuals with dysarthria. In Part 2, acoustic data are reviewed for dysarthria associated with Parkinson disease (PD), cerebellar disease, amytrophic lateral sclerosis, traumatic brain injury, unilateral hemispheric stroke, and essential tremor.…

Mitochondrial disorders: Challenges in diagnosis & treatment

PubMed Central

Khan, Nahid Akhtar; Govindaraj, Periyasamy; Meena, Angamuthu Kannan; Thangaraj, Kumarasamy

2015-01-01

Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment. PMID:25857492

New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance.

PubMed

Daiber, A; Wenzel, P; Oelze, M; Münzel, T

2008-01-01

Organic nitrates still represent a group of very effective anti-ischemic drugs used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. Long-term therapy with organic nitrates, however, results in a rapid development of nitrate tolerance blunting their hemodynamic and antiischemic efficacy. Recent studies revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role for the development of nitrate and crosstolerance. The present review focuses firstly on the role of ALDH-2 for organic nitrate bioactivation and secondly on the role of oxidative stress in the development of tolerance and cross-tolerance (endothelial dysfunction) in response to various organic nitrates. Finally, we would like to draw the reader's attention to the protective properties of the organic nitrate pentaerithrityl tetranitrate (PETN), which, in contrast to all other organic nitrates, is able to upregulate enzymes with a strong antioxidative capacity thereby preventing tolerance and the development of endothelial dysfunction.

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

PubMed Central

Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

2015-01-01

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

Innovative architecture design for high performance organic and hybrid multi-junction solar cells

NASA Astrophysics Data System (ADS)

Li, Ning; Spyropoulos, George D.; Brabec, Christoph J.

2017-08-01

The multi-junction concept is especially attractive for the photovoltaic (PV) research community owing to its potential to overcome the Schockley-Queisser limit of single-junction solar cells. Tremendous research interests are now focused on the development of high-performance absorbers and novel device architectures for emerging PV technologies, such as organic and perovskite PVs. It has been predicted that the multi-junction concept is able to boost the organic and perovskite PV technologies approaching the 20% and 30% benchmarks, respectively, showing a bright future of commercialization of the emerging PV technologies. In this contribution, we will demonstrate innovative architecture design for solution-processed, highly functional organic and hybrid multi-junction solar cells. A simple but elegant approach to fabricating organic and hybrid multi-junction solar cells will be introduced. By laminating single organic/hybrid solar cells together through an intermediate layer, the manufacturing cost and complexity of large-scale multi-junction solar cells can be significantly reduced. This smart approach to balancing the photocurrents as well as open circuit voltages in multi-junction solar cells will be demonstrated and discussed in detail.

Student Leadership in a Residential College: From Dysfunction to Effective Collaboration

ERIC Educational Resources Information Center

Bloomdahl, Susana Contreras; Navan, Joy

2013-01-01

This article depicts the intervention strategy of two faculty members on a dysfunctional student council in a residential college setting. The council demonstrated poor collaboration and productivity, which indicated signs of distrust. The group intervention helped to expose the students' lack of organization and need to learn more about each…

Aminoethyl nitrate – the novel super nitrate?

PubMed Central

Bauersachs, Johann

2009-01-01

Long-term use of most organic nitrates is limited by development of tolerance, induction of oxidative stress and endothelial dysfunction. In this issue of the BJP, Schuhmacher et al. characterized a novel class of organic nitrates with amino moieties (aminoalkyl nitrates). Aminoethyl nitrate was identified as a novel organic mononitrate with high potency but devoid of induction of mitochondrial oxidative stress. Cross-tolerance to nitroglycerin or the endothelium-dependent agonist acetylcholine after in vivo treatment was not observed. Like all nitrates, aminoethyl nitrate induced vasorelaxation by activation of soluble guanylate cyclase. Thus, in contrast to the prevailing view, high potency in an organic nitrate is not necessarily accompanied by induction of oxidative stress or endothelial dysfunction. This work from Daiber's group is an important step forward in the understanding of nitrate bioactivation, tolerance phenomena and towards the development of better organic nitrates for clinical use. PMID:19732062

The Role of Attention in Somatosensory Processing: A Multi-trait, Multi-method Analysis

PubMed Central

Puts, Nicolaas A. J.; Mahone, E. Mark; Edden, Richard A. E.; Tommerdahl, Mark; Mostofsky, Stewart H.

2016-01-01

Sensory processing abnormalities in autism have largely been described by parent report. This study used a multi-method (parent-report and measurement), multi-trait (tactile sensitivity and attention) design to evaluate somatosensory processing in ASD. Results showed multiple significant within-method (e.g., parent report of different traits)/cross-trait (e.g., attention and tactile sensitivity) correlations, suggesting that parent-reported tactile sensory dysfunction and performance-based tactile sensitivity describe different behavioral phenomena. Additionally, both parent-reported tactile functioning and performance-based tactile sensitivity measures were significantly associated with measures of attention. Findings suggest that sensory (tactile) processing abnormalities in ASD are multifaceted, and may partially reflect a more global deficit in behavioral regulation (including attention). Challenges of relying solely on parent-report to describe sensory difficulties faced by children/families with ASD are also highlighted. PMID:27448580

The outcomes and prognostic factors of acute respiratory failure in the patients 90 years old and over

PubMed Central

Kung, Shu-Chen; Wang, Ching-Min; Lai, Chih-Cheng; Chao, Chien-Ming

2018-01-01

This retrospective cohort study investigated the outcomes and prognostic factors in nonagenarians (patients 90 years old or older) with acute respiratory failure. Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring invasive mechanical ventilation (MV) were enrolled. Outcomes including in-hospital mortality and ventilator dependency were measured. A total of 173 nonagenarians with acute respiratory failure were admitted to the intensive care unit (ICU). A total of 56 patients died during the hospital stay and the rate of in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 % CI, 1.55-22.45; p = 0.009, APACHE II scores ≥ 25 vs APACHE II scores < 15), use of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; ≥ 3 organ dysfunction vs ≤ 1 organ dysfunction) were more likely to die. Among the 117 survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In conclusion, the mortality rate of nonagenarians with acute respiratory failure was high, especially for those with higher APACHE II scores or more organ dysfunction. PMID:29467961

Contemporary Patterns of Multiple Organ Dysfunction in Trauma.

PubMed

Shepherd, Joanna M; Cole, Elaine; Brohi, Karim

2017-04-01

Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold (≤5). Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P≤0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

PubMed

Boehne, Martin; Jack, Thomas; Köditz, Harald; Seidemann, Kathrin; Schmidt, Florian; Abura, Michaela; Bertram, Harald; Sasse, Michael

2013-02-06

Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. The incidence rates of respiratory (-5.06%; 95% CI, -9.52 to -0.59%), renal (-3.87%; 95% CI, -7.58 to -0.15%) and hematologic (-3.89%; 95% CI, -7.26 to -0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. ClinicalTrials.gov number; NCT00209768.

Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study

PubMed Central

2010-01-01

Introduction Transfusion is a common treatment in pediatric intensive care units (PICUs). Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome of critically ill children. Methods Prospective, observational study conducted in 30 North American centers, in consecutive patients aged <18 years with a stay ≥ 48 hours in a PICU. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and PICU length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model. Results The median length of storage was 14 days in 296 patients with documented length of storage. For patients receiving blood stored ≥ 14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, P = 0.03). There was also a significant difference in the total PICU length of stay (adjusted median difference +3.7 days, P < 0.001) and no significant change in mortality. Conclusions In critically ill children, transfusion of red blood cell units stored for ≥ 14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay. PMID:20377853

Identifying Pediatric Severe Sepsis and Septic Shock: Accuracy of Diagnosis Codes.

PubMed

Balamuth, Fran; Weiss, Scott L; Hall, Matt; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Centkowski, Sierra; Baumer-Mouradian, Shannon; Weiser, Jason; Hayes, Katie; Shah, Samir S; Alpern, Elizabeth R

2015-12-01

To evaluate accuracy of 2 established administrative methods of identifying children with sepsis using a medical record review reference standard. Multicenter retrospective study at 6 US children's hospitals. Subjects were children >60 days to <19 years of age and identified in 4 groups based on International Classification of Diseases, Ninth Revision, Clinical Modification codes: (1) severe sepsis/septic shock (sepsis codes); (2) infection plus organ dysfunction (combination codes); (3) subjects without codes for infection, organ dysfunction, or severe sepsis; and (4) infection but not severe sepsis or organ dysfunction. Combination codes were allowed, but not required within the sepsis codes group. We determined the presence of reference standard severe sepsis according to consensus criteria. Logistic regression was performed to determine whether addition of codes for sepsis therapies improved case identification. A total of 130 out of 432 subjects met reference SD of severe sepsis. Sepsis codes had sensitivity 73% (95% CI 70-86), specificity 92% (95% CI 87-95), and positive predictive value 79% (95% CI 70-86). Combination codes had sensitivity 15% (95% CI 9-22), specificity 71% (95% CI 65-76), and positive predictive value 18% (95% CI 11-27). Slight improvements in model characteristics were observed when codes for vasoactive medications and endotracheal intubation were added to sepsis codes (c-statistic 0.83 vs 0.87, P = .008). Sepsis specific International Classification of Diseases, Ninth Revision, Clinical Modification codes identify pediatric patients with severe sepsis in administrative data more accurately than a combination of codes for infection plus organ dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.

PubMed

Weiss, Scott L; Fitzgerald, Julie C; Balamuth, Fran; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M; Thomas, Neal J

2014-11-01

Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Retrospective observational study. PICU at an academic medical center. One hundred thirty patients treated for severe sepsis or septic shock. None. We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04). Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

Delayed Antimicrobial Therapy Increases Mortality and Organ Dysfunction Duration in Pediatric Sepsis

PubMed Central

Weiss, Scott L.; Fitzgerald, Julie C.; Balamuth, Fran; Alpern, Elizabeth R.; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M.; Thomas, Neal J.

2014-01-01

Objectives Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Design Retrospective observational study. Setting PICU at an academic medical center. Patients One hundred thirty patients treated for severe sepsis or septic shock. Interventions None. Measurements and Main Results We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure–free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74–277 min) and to first appropriate antimicrobial was 177 minutes (90–550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27–12.06) and 3.59 (95% CI, 1.09–11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45–16.2) and 4.92 (95% CI, 1.30–18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure–free days (16 [interquartile range, 1–23] vs 20 [interquartile range, 6–26]; p = 0.04). Conclusions Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis. PMID:25148597

Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue

PubMed Central

Boengler, Kerstin; Kosiol, Maik; Mayr, Manuel; Schulz, Rainer

2017-01-01

Abstract Age is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best‐known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high‐energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed. PMID:28432755

Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2014-04-16

The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems. Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD. The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.

STAT3 in the Systemic Inflammation of Cancer Cachexia

PubMed Central

Zimmers, Teresa A.; Fishel, Melissa L.; Bonetto, Andrea

2016-01-01

Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both contributory and protective functions for STAT3 in other organs during cachexia. Finally, STAT3 contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia in cancer and evidence for targeting STAT3 for anti-cachexia therapies. PMID:26860754

[The relationship of attachment features and multi-impulsive symptoms in eating disorders].

PubMed

Szalai, Tamás Dömötör

2017-07-01

Attachment dysfunctions determine borderline personality disorder, which is a frequent background factor of multi-impulsivity; however, the relationship between attachment and multi-impulsive eating disorders is almost unexplored. To compare attachment features of multi-impulsive and classical eating disorder patients with individuals without eating disorders, and to test attachment as a predictor of multi-impulsivity. A cross-sectional survey (148 females, mean age: 30.9 years) investigated maternal, paternal and adult attachment, depression, anxiety, eating disorder and multi-impulsive symptoms in these groups. Altogether 41.3% of the individuals without eating disorders, 17.6% of classical and 11.8% of multi-impulsive eating disorder patients had secure attachment. Multi-impulsive patients had the most severe eating disorder symptoms (F (2) = 17.733) and the lowest paternal care (F (2) = 3.443). Preoccupied and fearful attachment explained 14.5% of multi-impulsive symptoms; however, with adjustment for depression only latter one remained the predictor of multi-impulsivity (t = 5.166, p<0.01). Multi-impulsives are a distinct subgroup of eating disorder patients from the aspects of both symptoms and attachment. Handling their negative moods may hold therapeutic potentials. Longitudinal studies are required to investigate the therapeutic value of paternal care, attachment preoccupation and fearfulness. Orv Hetil. 2017; 158(27): 1058-1066.

Pelvic Floor Physical Therapy and Women's Health Promotion.

PubMed

Lawson, Samantha; Sacks, Ashley

2018-05-19

Pelvic floor dysfunction is defined as abnormal function of the pelvic floor and includes conditions that can have significant adverse impacts on a woman's quality of life, including urinary incontinence (stress, urge, and mixed), fecal incontinence, pelvic organ prolapse, sexual dysfunction, diastasis recti abdominis, pelvic girdle pain, and chronic pain syndromes. Women's health care providers can screen for, identify, and treat pelvic floor dysfunction. This article examines the case of a woman with multiple pelvic-floor-related problems and presents the evidence for the use of pelvic floor physical therapy (PFPT) for pregnancy-related pelvic floor dysfunction. PFPT is an evidence-based, low-risk, and minimally invasive intervention, and women's health care providers can counsel women about the role that PFPT may play in the prevention, treatment, and/or management of pelvic floor dysfunction. © 2018 by the American College of Nurse-Midwives.

A Motion-Sensing Game-Based Therapy to Foster the Learning of Children with Sensory Integration Dysfunction

ERIC Educational Resources Information Center

Chuang, Tsung-Yen; Kuo, Ming-Shiou

2016-01-01

Children with Sensory Integration Dysfunction (SID, also known as Sensory Processing Disorder, SPD) are also learners with disabilities with regard to responding adequately to the demands made by a learning environment. With problems of organizing and processing the sensation information coming from body modalities, children with SID (CwSID)…

Unification of multi-species vertebrate anatomy ontologies for comparative biology in Uberon

PubMed Central

2014-01-01

Background Elucidating disease and developmental dysfunction requires understanding variation in phenotype. Single-species model organism anatomy ontologies (ssAOs) have been established to represent this variation. Multi-species anatomy ontologies (msAOs; vertebrate skeletal, vertebrate homologous, teleost, amphibian AOs) have been developed to represent ‘natural’ phenotypic variation across species. Our aim has been to integrate ssAOs and msAOs for various purposes, including establishing links between phenotypic variation and candidate genes. Results Previously, msAOs contained a mixture of unique and overlapping content. This hampered integration and coordination due to the need to maintain cross-references or inter-ontology equivalence axioms to the ssAOs, or to perform large-scale obsolescence and modular import. Here we present the unification of anatomy ontologies into Uberon, a single ontology resource that enables interoperability among disparate data and research groups. As a consequence, independent development of TAO, VSAO, AAO, and vHOG has been discontinued. Conclusions The newly broadened Uberon ontology is a unified cross-taxon resource for metazoans (animals) that has been substantially expanded to include a broad diversity of vertebrate anatomical structures, permitting reasoning across anatomical variation in extinct and extant taxa. Uberon is a core resource that supports single- and cross-species queries for candidate genes using annotations for phenotypes from the systematics, biodiversity, medical, and model organism communities, while also providing entities for logical definitions in the Cell and Gene Ontologies. The ontology release files associated with the ontology merge described in this manuscript are available at: http://purl.obolibrary.org/obo/uberon/releases/2013-02-21/ Current ontology release files are available always available at: http://purl.obolibrary.org/obo/uberon/releases/ PMID:25009735

A novel approach to mesh revision after sacrocolpopexy.

PubMed

Dawson, Melissa L; Rebecca, Rinko; Shah, Nima M; Whitmore, Kristene E

2016-01-01

Pelvic organ prolapse (POP) is the herniation of pelvic organs to or beyond the vaginal walls. POP affects 50% of parous women; of those women, 11% will need surgery based on bothersome symptoms. Transvaginal mesh has been used for vaginal augmentation since the 1990s. Complications from mesh use are now more prominent, and include chronic pelvic pain, dyspareunia, vaginal mesh erosion, and urinary and defecatory dysfunction. Presently, there is no consensus regarding treatment of these complications. Reported herein are two cases of women with defecatory dysfunction and pain after sacrocolpopexy who underwent mesh revision procedures performed with both urogynecologic and colorectal surgery.

Autodigestion: Proteolytic Degradation and Multiple Organ Failure in Shock

PubMed Central

Altshuler, Angelina E.; Kistler, Erik B.; Schmid-Schönbein, Geert W.

2015-01-01

There is currently no effective treatment for multiorgan failure following shock other than alleviation supportive care. A better understanding of the pathogenesis of these sequelae to shock is required. The intestine plays a central role in multiorgan failure. It was previously suggested that bacteria and their toxins are responsible for the organ failure seen in circulatory shock, but clinical trials in septic patients have not confirmed this hypothesis. Instead, we review here evidence that the digestive enzymes, synthesized in the pancreas and discharged into the small intestine as requirement for normal digestion, may play a role in multi-organ failure. These powerful enzymes are non-specific, highly concentrated and fully activated in the lumen of the intestine. During normal digestion they are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. However, if this barrier becomes permeable, e.g. in an ischemic state, the digestive enzymes escape into the wall of the intestine. They digest tissues in the mucosa and generate small molecular weight cytotoxic fragments such as unbound free fatty acids. Digestive enzymes may also escape into the systemic circulation and activate other degrading proteases. These proteases have the ability to clip the ectodomain of surface receptors and compromise their function; for example cleaving the insulin receptor causing insulin resistance. The combination of digestive enzymes and cytotoxic fragments leaking into the central circulation causes cell and organ dysfunction, and ultimately may lead to complete organ failure and death. We summarize current evidence suggesting that enteral blockade of digestive enzymes inside the lumen of the intestine may serve to reduce acute cell and organ damage and improve survival in experimental shock. PMID:26717111

Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

PubMed

Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

2017-07-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P < 0·001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Self Organized Multi Agent Swarms (SOMAS) for Network Security Control

DTIC Science & Technology

2009-03-01

Normal hierarchy vs entangled hierarchy 2.5.7 Quantifying Entangledness . While self organization means that the swarm develops a consistent structure of...flexibility due to centralization of control and com- munication. Thus, self organized, entangled hierarchy multi-agent swarms are evolved in this study to...technique. The resulting design exhibits a self organized multi-agent swarm (SOMAS) with entangled hierarchical control and communication through the

Sexual dysfunction and neuroendocrine correlates of posttraumatic stress disorder in combat veterans: Preliminary findings.

PubMed

Lehrner, Amy; Flory, Janine D; Bierer, Linda M; Makotkine, Iouri; Marmar, Charles R; Yehuda, Rachel

2016-01-01

Sexual dysfunction is not a symptom of PTSD but is a common clinical complaint in trauma survivors with this disorder. In that there are biological parallels in the neuroendocrine processes underlying both PTSD and sexual behavior, we conducted an exploratory investigation of the relationship of PTSD and related neuroendocrine indicators with sexual dysfunction in armed service veterans. Major Depressive Disorder, highly comorbid with PTSD and sexual dysfunction, was also assessed. In veterans with PTSD, sexual problems were associated with plasma DHEA and cortisol, urinary catecholamines, and glucocorticoid sensitivity, even when controlling for the effects of comorbid depression. In a subsample analysis, testosterone levels did not distinguish PTSD or sexual dysfunction, suggesting that sexual problems reported by veterans in this sample were not the result of organic disorder. PTSD did predict higher dihydrotestosterone (DHT) levels, which were associated with sexual problems. More detailed assessment of sexual dysfunction in biologically informed studies of PTSD is warranted to clarify the relationships of PTSD symptomatology and related neurobiology with sexual dysfunction. Published by Elsevier Ltd.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction

PubMed Central

de Matos, Ana Cristina Carvalho; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; de Arruda, Érika Ferraz; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

2015-01-01

ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

Hypomagnesemia and mild rhabdomyolysis in living related donor renal transplant recipient treated with cyclosporine A.

PubMed

Cavdar, C; Sifil, A; Sanli, E; Gülay, H; Camsari, T

1998-12-01

Since cyclosporine A (CsA) had been used in renal transplant recipients, important improvements in short-term and long-term graft survivals have been detected. In spite of these improvements CsA seems to have several adverse effects. First, CsA leads to nephrotoxicity. Moreover, CsA affects the other organs and systems (skin, liver, nervous system, etc.) and causes, increased risks of infections and malignancies. Hypomagnesemia is one of the side effects of CsA therapy, but it is a rare condition in living related donor renal transplant recipients. It may also cause multi-system dysfunction, especially hypocalcemia and hypokalemia, which cannot be corrected without magnesium therapy. In addition, rhabdomyolysis was detected in animals, but it has not been reported in living related donor renal transplant recipients. In this case report, a living related donor renal transplant recipient who suffered from hypomagnesemia and mild rhabdomyolysis due to CsA therapy will be described and discussed.

Data-driven modelling of social forces and collective behaviour in zebrafish.

PubMed

Zienkiewicz, Adam K; Ladu, Fabrizio; Barton, David A W; Porfiri, Maurizio; Bernardo, Mario Di

2018-04-14

Zebrafish are rapidly emerging as a powerful model organism in hypothesis-driven studies targeting a number of functional and dysfunctional processes. Mathematical models of zebrafish behaviour can inform the design of experiments, through the unprecedented ability to perform pilot trials on a computer. At the same time, in-silico experiments could help refining the analysis of real data, by enabling the systematic investigation of key neurobehavioural factors. Here, we establish a data-driven model of zebrafish social interaction. Specifically, we derive a set of interaction rules to capture the primary response mechanisms which have been observed experimentally. Contrary to previous studies, we include dynamic speed regulation in addition to turning responses, which together provide attractive, repulsive and alignment interactions between individuals. The resulting multi-agent model provides a novel, bottom-up framework to describe both the spontaneous motion and individual-level interaction dynamics of zebrafish, inferred directly from experimental observations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tropic Lightning: Myth or Menace?

PubMed Central

2014-01-01

Lightning is one of the leading causes of death related to environmental disaster. Of all lightning fatalities documented between 2006 and 2012, leisure activities contributed the largest proportion of deaths, with water-associated, sports, and camping being the most common. Despite the prevalence of these activities throughout the islands, Hawai‘i has had zero documented lightning fatalities since weather data tracking was initiated in 1959. There is a common misconception that lightning does not strike the ground in Hawai‘i. This myth may contribute to a potentially dangerous false sense of security, and recognition of warning signs and risk factor modification remain the most important prevention strategies. Lightning damage occurs on a spectrum, from minor burns to multi-organ dysfunction. After injury, initial treatment should focus on “reverse triage” and immediate cardiopulmonary resuscitation when indicated, followed by transfer to a healthcare facility. Definitive treatment entails monitoring and management of potential sequelae, to include cardiovascular, neurologic, dermatologic, ophthalmologic, audiovestibular, and psychiatric complications. PMID:25478304

Multi-Team and Multi-Organization Systems

DTIC Science & Technology

2009-11-01

Irandoust, A. Benaskeur ; DRDC Valcartier TR 2009-198 ; Recherche et développement pour la défense Canada – Valcartier ; novembre 2009. Contexte...defining features . . . . . . . . . . . . . . . . . 13 3.2.1 Purpose of Partnership . . . . . . . . . . . . . . . . . . . . . . . . 14 3.2.2 Control...the spectrum of organizations . . . . . . . 11 Figure 3: Properties of emergent and planned multi-organization systems . . . . . 13 Figure 4: Costs

[Inversion of organic matter content of the north fluvo-aquic soil based on hyperspectral and multi-spectra].

PubMed

Wang, Yan-Cang; Gu, Xiao-He; Zhu, Jin-Shan; Long, Hui-Ling; Xu, Peng; Liao, Qin-Hong

2014-01-01

The present study aims to assess the feasibility of multi-spectral data in monitoring soil organic matter content. The data source comes from hyperspectral measured under laboratory condition, and simulated multi-spectral data from the hyperspectral. According to the reflectance response functions of Landsat TM and HJ-CCD (the Environment and Disaster Reduction Small Satellites, HJ), the hyperspectra were resampled for the corresponding bands of multi-spectral sensors. The correlation between hyperspectral, simulated reflectance spectra and organic matter content was calculated, and used to extract the sensitive bands of the organic matter in the north fluvo-aquic soil. The partial least square regression (PLSR) method was used to establish experiential models to estimate soil organic matter content. Both root mean squared error (RMSE) and coefficient of the determination (R2) were introduced to test the precision and stability of the modes. Results demonstrate that compared with the hyperspectral data, the best model established by simulated multi-spectral data gives a good result for organic matter content, with R2=0.586, and RMSE=0.280. Therefore, using multi-spectral data to predict tide soil organic matter content is feasible.

Urological complications of uterine leiomyoma: a review of literature.

PubMed

Dagur, Gautam; Suh, Yiji; Warren, Kelly; Singh, Navjot; Fitzgerald, John; Khan, Sardar A

2016-06-01

Uterine leiomyomas are common gynecologic tumor in reproductive-aged women, by age 50, diagnosis shared by urologist, gynecologists and radiologists. The goal of this article is to review the current literature, study the impact of leiomyoma on female lower urinary tract, examine the cause female sexual dysfunction and provide a comprehensive review of current diagnostic, imaging studies, and current treatment of leiomyoma. Clinical leiomyoma studies published from 1956 through 2015 were identified using the PubMed search engines and the key words leiomyoma, fibroid in the current literature. Impact of leiomyoma on the lower urinary tract including female sexual dysfunction was reviewed with terms of "urinary retention", "bladder", "urethra", "dyspareunia", "incontinence", "incomplete bladder emptying", "female sexual dysfunction", and "lower urinary tract" to study the urological and sexual effects of leiomyoma. Literature related to leiomyoma was reviewed from 1965 to present. Women with uterine leiomyomata complained of pelvic pain, menstrual irregularities, infertility, lower urinary tract symptoms and sexual dysfunction. Leiomyoma is a common tumor of the uterus that often clinically impacts on the lower urinary tract and results in urological and sexual symptoms. Leiomyoma can compress and grow into and become adherent to the bladder and surrounding pelvic organs or metastasize into peritoneal organs. Leiomyoma can enlarge and compress the urinary bladder, urethra, and lower end of the ureters. Leiomyoma can cause embarrassing sexual dysfunction in females. Current literature of non-surgical and surgical therapy of leiomyoma is described.

A Quantum Approach to Multi-Agent Systems (MAS), Organizations, and Control

DTIC Science & Technology

2003-06-01

interdependent interactions between individuals represented approximately as vocal harmonic I resonators. Then the growth rate of an organization fits ...A quantum approach to multi-agent systems (MAS), organizations , and control W.F. Lawless Paine College 1235 15th Street Augusta, GA 30901...AND SUBTITLE A quantum approach to multi-agent systems (MAS), organizations , and control 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

A case of erectile dysfunction and risk factors for coronary artery disease.

PubMed

Kloner, R A

2005-12-01

The hypothetical case of a man with erectile dysfunction and multiple cardiovascular risk factors is presented to illustrate the use of the second Princeton Consensus Conference Guidelines. Methods to optimize efficacy of the phosphodiesterase inhibitors are described. The overall cardiovascular safety of the phosphodiesterase inhibitors and their interaction with organic nitrates and alpha blockers are discussed.

The Neurophysiology of Autonomic Dysfunction in SCI: Plasticity in the Input and Output Neurons

DTIC Science & Technology

2014-04-01

multi-segmental spinal pain reflex Location: Halls B-H Presentation Time: Tuesday , Nov 16, 2010, 8:00 AM - 9:00 AM Authors: *K. E. TANSEY1, M...neurological scoring methods. Cognitive functions were tested using Fear Conditioning tests at 8–10 days post- injury and Morris Water Maze tests 11–15

Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma).

PubMed

Pirie, R S; Collie, D D S; Dixon, P M; McGorum, B C

2003-05-01

Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. Heaves-susceptible horses also received inhalation challenge with HDS particulates with and without the addition of LPS and were housed in two separate dusty environments during which mould and endotoxin exposure was measured. The airway inflammatory and functional response to each challenge was measured. Depletion of endotoxin from HDS attenuated the airway neutrophilia and abrogated the airway dysfunction induced in heaves horses by inhaled HDS. The airway response was re-established by adding back LPS to the depleted HDS, confirming that the attenuation in airway response was due specifically to endotoxin depletion. Interestingly, the magnitude of alteration in airway response following endotoxin depletion and add-back was greater than that which could be attributed solely to endotoxin per se, indicating that the LPS activity was enhanced by the other dust components. Consistent with this possibility, washed particulates harvested from HDS enhanced the airway response to inhaled LPS in heaves horses. Heaves horses given two different hay/straw challenges had a significantly different severity of airway inflammation and dysfunction, despite airborne dust and endotoxin concentrations in the horses' breathing zones being similar. Although inhaled endotoxin appears not to be the only determinant of disease severity in heaves, it does contribute significantly to the induction of airway inflammation and dysfunction. This contribution is largely via the synergistic action of inhaled endotoxin and organic dust particulates, although other soluble dust components also contribute to a lesser degree.

From neurocognition to community participation in serious mental illness: the intermediary role of dysfunctional attitudes and motivation.

PubMed

Thomas, E C; Luther, L; Zullo, L; Beck, A T; Grant, P M

2017-04-01

Evidence for a relationship between neurocognition and functional outcome in important areas of community living is robust in serious mental illness research. Dysfunctional attitudes (defeatist performance beliefs and asocial beliefs) have been identified as intervening variables in this causal chain. This study seeks to expand upon previous research by longitudinally testing the link between neurocognition and community participation (i.e. time in community-based activity) through dysfunctional attitudes and motivation. Adult outpatients with serious mental illness (N = 175) participated, completing follow-up assessments approximately 6 months after initial assessment. Path analysis tested relationships between baseline neurocognition, emotion perception, functional skills, dysfunctional attitudes, motivation, and outcome (i.e. community participation) at baseline and follow-up. Path models demonstrated two pathways to community participation. The first linked neurocognition and community participation through functional skills, defeatist performance beliefs, and motivation. A second pathway linked asocial beliefs and community participation, via a direct path passing through motivation. Model fit was excellent for models predicting overall community participation at baseline and, importantly, at follow-up. The existence of multiple pathways to community participation in a longitudinal model supports the utility of multi-modal interventions for serious mental illness (i.e. treatment packages that build upon individuals' strengths while addressing the array of obstacles to recovery) that feature dysfunctional attitudes and motivation as treatment targets.

Multiple organ dysfunction syndrome, an unusual complication of heroin intoxication: a case report and review of literature.

PubMed

Feng, Gang; Luo, Qiancheng; Guo, Enwei; Yao, Yulan; Yang, Feng; Zhang, Bingyu; Li, Longxuan

2015-01-01

Multiple organ dysfunction syndrome (MODS) has rarely been described in patients with heroin intoxication. Here, we report a rare case of MODS involving six organs, due to heroin intoxication. The patient was a 32-year-old Chinese man with severe heroin intoxication complicated by acute pulmonary edema and respiratory insufficiency, shock, myocardial damage and cardiac insufficiency, rhabdomyolysis and acute renal insufficiency, acute liver injury and hepatic insufficiency, toxic leukoencephalopathy, and hypoglycemia. He managed to survive and was discharged after 10 weeks of intensive care. The possible pathogenesis and therapeutic measures of MODS induced by heroin intoxication and some suggestions for preventing and treating severe complications of heroin intoxication, based on clinical evidence and the pertinent literature, are discussed in this report.

The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.

PubMed

Lowes, Damon A; Thottakam, Bensita M V; Webster, Nigel R; Murphy, Michael P; Galley, Helen F

2008-12-01

Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondrial membrane potential was augmented (P<0.01) in most organs. These findings suggest that the use of mitochondria-targeted antioxidants such as MitoQ may be beneficial in sepsis.

Multiscale Analysis of a Collapsible Respiratory Airway

NASA Astrophysics Data System (ADS)

Ghadiali, Samir; Bell, E. David; Swarts, J. Douglas

2006-11-01

The Eustachian tube (ET) is a collapsible respiratory airway that connects the nasopharynx with the middle ear (ME). The ET normally exists in a collapsed state and must be periodically opened to maintain a healthy and sterile ME. Although the inability to open the ET (i.e. ET dysfunction) is the primary etiology responsible for several common ME diseases (i.e. Otitis Media), the mechanisms responsible for ET dysfunction are not well established. To investigate these mechanisms, we developed a multi-scale model of airflow in the ET and correlated model results with experimental data obtained in healthy and diseased subjects. The computational models utilized finite-element methods to simulate fluid-structure interactions and molecular dynamics techniques to quantify the adhesive properties of mucus glycoproteins. Results indicate that airflow in the ET is highly sensitive to both the dynamics of muscle contraction and molecular adhesion forces within the ET lumen. In addition, correlation of model results with experimental data obtained in diseased subjects was used to identify the biomechanical mechanisms responsible for ET dysfunction.

The associations between multisensory temporal processing and symptoms of schizophrenia.

PubMed

Stevenson, Ryan A; Park, Sohee; Cochran, Channing; McIntosh, Lindsey G; Noel, Jean-Paul; Barense, Morgan D; Ferber, Susanne; Wallace, Mark T

2017-01-01

Recent neurobiological accounts of schizophrenia have included an emphasis on changes in sensory processing. These sensory and perceptual deficits can have a cascading effect onto higher-level cognitive processes and clinical symptoms. One form of sensory dysfunction that has been consistently observed in schizophrenia is altered temporal processing. In this study, we investigated temporal processing within and across the auditory and visual modalities in individuals with schizophrenia (SCZ) and age-matched healthy controls. Individuals with SCZ showed auditory and visual temporal processing abnormalities, as well as multisensory temporal processing dysfunction that extended beyond that attributable to unisensory processing dysfunction. Most importantly, these multisensory temporal deficits were associated with the severity of hallucinations. This link between atypical multisensory temporal perception and clinical symptomatology suggests that clinical symptoms of schizophrenia may be at least partly a result of cascading effects from (multi)sensory disturbances. These results are discussed in terms of underlying neural bases and the possible implications for remediation. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of compartment defects in anorectal and pelvic floor dysfunction with female outlet obstruction constipation (OOC) by dynamic MR defecography.

PubMed

Li, M; Jiang, T; Peng, P; Yang, X-Q; Wang, W-C

2015-04-01

Chronic constipation affects more than 17% of the global population worldwide, and up to 50% of patients were outlet obstruction constipation (OOC). Women and the elderly are most likely to be affected, due to female-specific risk factors, such as menopause, parity and multiparity. The aim of our study was to investigate the association of compartment defects in anorectal and pelvic floor dysfunction with female outlet obstruction constipation (OOC) by MR defecography. Fifty-six consecutive women diagnosed with outlet obstruction constipation from October 2009 to July 2011 were included. They were categorized into the following groups: anorectal disorder only group (27 patients) and anorectal disorder plus multi-compartment pelvic disorder group (29 patients). Relevant measurements were taken at rest, during squeezing and straining. Anismus was significantly more common in the anorectal disorder group compared to the multi-compartment pelvic disorder group. Conversely, rectocele, rectal prolapse, and descending perineum were significantly more common in the multi-compartment pelvic disorder group compared to the anorectal disorder group. Of the total 56 OOC patients, 34 (60.7%) exhibited anismus and 38 (67.9%) rectocele. Among the anismus patients, there were 8 patients (23.5%) with combined cystocele, and 6 patients (17.6%) with combined vaginal/cervical prolapse. Among the rectocele patients, there were 23 patients (60.5%) with combined cystocele and 18 patients (47.4%) with combined vaginal/cervical prolapse. With respect to anorectal defects, 13 anismus patients (38.2%) were with signal posterior pelvic defects, 4 rectocele patients (10.5%) presented with signal posterior pelvic defects. Inadequate defecatory propulsion due to outlet obstruction constipation is often associated with multi-compartment pelvic floor disorders, whereas not about dyssynergic defecation.

Investigation of erectile dysfunction.

PubMed

Patel, D V; Halls, J; Patel, U

2012-11-01

Erectile dysfunction (ED) represents a common and debilitating condition with a wide range of organic and non-organic causes. Physical aetiologies can be divided into disorders affecting arterial inflow, the venous occlusion mechanism or the penile structure itself. Various imaging modalities can be utilised to investigate the physical causes of ED, but penile Doppler sonography (PDS) is the most informative technique, indicated in those patients with ED who do not respond to oral pharmacological agents (e.g. phosphodiesterase type 5 inhibitors). This review will examine the anatomical and physiological basis of penile erection, the method for performing PDS and features of specific causes of ED, and will also consider the alternative imaging modalities available.

Review: Pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction.

PubMed

Santoro, Domenico; Marsella, Rosanna; Pucheu-Haston, Cherie M; Eisenschenk, Melissa N C; Nuttall, Tim; Bizikova, Petra

2015-04-01

Canine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The pathogenesis of canine AD is incompletely understood. The aim of this review is to provide an in-depth update on the involvement of skin barrier and host-microbiome interaction in the pathogenesis of canine AD. Online citation databases and abstracts from international meetings were searched for publications related to skin barrier and host-microbiome interaction (e.g. bacteria, yeast, antimicrobial peptides). A total of 126 publications were identified. This review article focuses on epidermal barrier dysfunction and the interaction between cutaneous microbes (bacteria and yeasts) and the host (antimicrobial peptides). Epidemiological updates on the presence of pathogenic organisms and canine AD are also provided. Major advances have been made in the investigation of skin barrier dysfunction in canine AD, although many questions still remain. Skin barrier dysfunction and host-microbiome interactions are emerging as primary alterations in canine AD. Based on this review, it is clear that future studies focused on the development of drugs able to restore the skin barrier and increase the natural defences against pathogenic organisms are needed. © 2015 ESVD and ACVD.

Informatics approaches in the Biological Characterization of ...

EPA Pesticide Factsheets

Adverse Outcome Pathways (AOPs) are a conceptual framework to characterize toxicity pathways by a series of mechanistic steps from a molecular initiating event to population outcomes. This framework helps to direct risk assessment research, for example by aiding in computational prioritization of chemicals, genes, and tissues relevant to an adverse health outcome. We have designed and implemented a computational workflow to access a wealth of public data relating genes, chemicals, diseases, pathways, and species, to provide a biological context for putative AOPs. We selected three AOP case studies: ER/Aromatase Antagonism Leading to Reproductive Dysfunction, AHR1 Activation Leading to Cardiotoxicity, and AChE Inhibition Leading to Acute Mortality, and deduced a taxonomic range of applicability for each AOP. We developed computational tools to automatically access and analyze the pathway activity of AOP-relevant protein orthologs, finding broad similarity among vertebrate species for the ER/Aromatase and AHR1 AOPs, and similarity extending to invertebrate animal species for AChE inhibition. Additionally, we used public gene expression data to find groups of highly co-expressed genes, and compared those groups across organisms. To interpret these findings at a higher level of biological organization, we created the AOPdb, a relational database that mines results from sources including NCBI, KEGG, Reactome, CTD, and OMIM. This multi-source database connects genes,

Antioxidants in critical care medicine.

PubMed

Coleman, N A

2001-09-01

Critically ill patients in the intensive care unit (ICU) present with a variety of different pathologies, and mortality is high despite extensive multi-organ supportive treatment. Reactive oxygen species (ROS) are believed to play a pivotal role in the pathophysiology of organ dysfunction in the ICU. In particular, the role of ROS as a final common pathway of cell damage has been increasingly emphasised in the adult respiratory distress syndrome (ARDS), in central nervous system traumatic and hypoxic states, and as a cause of ischaemic neurological deficits after subarachnoid haemorrhage. Measurement of total antioxidant status (TAS) has shown improved survival of patients with high TAS and poorer outcomes for those with lower values. Attempts to supplement endogenous antioxidant defences have not demonstrated clear benefits in randomised clinical trials, and the use of free radical scavenging agents have had similar mixed results. Considering the wide variation in the nature and severity of illness in the intensive care population, it is not surprising that clear evidence of the efficacy of antioxidant therapies in improving survival has not been clearly demonstrated. However, single component therapies for complex pathophysiological processes are rarely successful, and the role of antioxidants in the critically ill should be thought of as only part of a rational and logical therapeutic approach.

Successful outcome after intravenous gasoline injection.

PubMed

Domej, Wolfgang; Mitterhammer, Heike; Stauber, Rudolf; Kaufmann, Peter; Smolle, Karl Heinz

2007-12-01

Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection. Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility. Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae.

Bacteria, Yeast, Worms, and Flies: Exploiting simple model organisms to investigate human mitochondrial diseases

PubMed Central

Rea, Shane L.; Graham, Brett H.; Nakamaru-Ogiso, Eiko; Kar, Adwitiya; Falk, Marni J.

2013-01-01

The extensive conservation of mitochondrial structure, composition, and function across evolution offers a unique opportunity to expand our understanding of human mitochondrial biology and disease. By investigating the biology of much simpler model organisms, it is often possible to answer questions that are unreachable at the clinical level. Here, we review the relative utility of four different model organisms, namely the bacteria Escherichia coli, the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, in studying the role of mitochondrial proteins relevant to human disease. E. coli are single cell, prokaryotic bacteria that have proven to be a useful model system in which to investigate mitochondrial respiratory chain protein structure and function. S. cerevisiae is a single-celled eukaryote that can grow equally well by mitochondrial-dependent respiration or by ethanol fermentation, a property that has proven to be a veritable boon for investigating mitochondrial functionality. C. elegans is a multi-cellular, microscopic worm that is organized into five major tissues and has proven to be a robust model animal for in vitro and in vivo studies of primary respiratory chain dysfunction and its potential therapies in humans. Studied for over a century, D. melanogaster is a classic metazoan model system offering an abundance of genetic tools and reagents that facilitates investigations of mitochondrial biology using both forward and reverse genetics. The respective strengths and limitations of each species relative to mitochondrial studies are explored. In addition, an overview is provided of major discoveries made in mitochondrial biology in each of these four model systems. PMID:20818735

Hypopituitarism in pediatric survivors of inflicted traumatic brain injury.

PubMed

Auble, Bethany A; Bollepalli, Sureka; Makoroff, Kathi; Weis, Tammy; Khoury, Jane; Colliers, Tracy; Rose, Susan R

2014-02-15

Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population (p<0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed.

Erectile dysfunction

PubMed Central

Yafi, Faysal A.; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M.; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J.; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P.; Hellstrom, Wayne J. G.

2016-01-01

Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man’s quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner’s sexual experience and the couple’s quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

How Multi-Organ Microdevices Can Help Foster Drug Development

PubMed Central

Esch, Mandy B.; Smith, Alec; Prot, Jean-Matthieu; Sancho, Carlotta Oleaga; Hickman, James; Shuler, Michael L.

2014-01-01

Multi-organ microdevices can mimic tissue-tissue interactions that occur as a result of metabolite travel from one tissue to other tissues in vitro. These systems are capable of simulating human metabolism, including the conversion of a pro-drug to its effective metabolite as well as its subsequent therapeutic actions and toxic side effects. Since tissue-tissue interactions in the human body can play a significant role in determining the success of new pharmaceuticals, the development and use of multi-organ microdevices presents an opportunity to improve the drug development process. The goals are to predict potential toxic side effects with higher accuracy before a drug enters the expensive phase of clinical trials as well as to estimate efficacy and dose response. Multi-organ microdevices also have the potential to aid in the development of new therapeutic strategies by providing a platform for testing in the context of human metabolism (as opposed to animal models). Further, when operated with human biopsy samples, the devices could be a gateway for the development of individualized medicine. Here we review studies in which multi-organ microdevices have been developed and used in a ways that demonstrate how the devices’ capabilities can present unique opportunities for the study of drug action. We also discuss the challenges that are inherent in the development of multi-organ microdevices. Among these are how to design the devices, and how to create devices that mimic the human metabolism with high authenticity. Since single organ devices are testing platforms for tissues that can later be combined with other tissues within multi-organ devices, we will also mention single organ devices where appropriate in the discussion. PMID:24412641

Renocardiac syndromes: physiopathology and treatment stratagems.

PubMed

Kingma, J G; Simard, D; Rouleau, J R

2015-01-01

Bidirectional inter-organ interactions are essential for normal functioning of the human body; however, they may also promote adverse conditions in remote organs. This review provides a narrative summary of the epidemiology, physiopathological mechanisms and clinical management of patients with combined renal and cardiac disease (recently classified as type 3 and 4 cardiorenal syndrome). Findings are also discussed within the context of basic research in animal models with similar comorbidities. Pertinent published articles were identified by literature search of PubMed, MEDLINE and Google Scholar. Additional data from studies in the author's laboratory were also consulted. The prevalence of renocardiac syndrome throughout the world is increasing in part due to an aging population and to other risk factors including hypertension, diabetes and dyslipidemia. Pathogenesis of this disorder involves multiple bidirectional interactions between the kidneys and heart; however, participation of other organs cannot be excluded. Our own work supports the hypothesis that the uremic milieu, caused by kidney dysfunction, produces major alterations in vasoregulatory control particularly at the level of the microvasculature that results in impaired oxygen delivery and blood perfusion. Recent clinical literature is replete with articles discussing the necessity to clearly define or characterize what constitutes cardiorenal syndrome in order to improve clinical management of affected patients. Patients are treated after onset of symptoms with limited available information regarding etiology. While understanding of mechanisms involved in pathogenesis of inter-organ crosstalk remains a challenging objective, basic research data remains limited partly because of the lack of animal models. Preservation of microvascular integrity may be the most critical factor to limit progression of multi-organ disorders including renocardiac syndrome. More fundamental studies are needed to help elucidate physiopathological mechanisms and for development of treatments to improve clinical outcomes.

Nonprescription analgesics and their use in solid-organ transplantation: a review.

PubMed

Gabardi, Steven; Luu, Linh

2004-09-01

To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. English-language studies were selected for inclusion. Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction. A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

Evaluation of the Causes of Erectile Dysfunction in Patients Undergoing Penile Doppler Ultrasonography in Pakistan

PubMed Central

Khanzada, Usman; Khan, Sohail Ahmed; Hussain, Munawar; Adel, Hatem; Masood, Kamran; Manohar, Murli

2017-01-01

Purpose In patients with erectile dysfunction, it is important to differentiate psychogenic from organic causes. Penile Doppler ultrasonography is a relatively inexpensive and minimally invasive tool for this purpose. This study was conducted to evaluate the causes of erectile dysfunction in an adult male population, using penile Doppler ultrasonography. Materials and Methods A retrospective study was conducted in a single center. All patients who presented with complaints of erectile dysfunction and underwent penile Doppler ultrasonography between July 2014 and June 2016 were included in this study. All examinations were performed using GE Voluson S6 and GE Logiq P5 devices. Following baseline scans, an intracavernosal injection of 20 µg of prostaglandin E1 was given. Peak systolic and end diastolic velocities were measured in each cavernosal artery. Patients with a peak systolic velocity of <25 cm/s were considered to have arterial insufficiency, while an end diastolic velocity of >5 cm/s was considered to indicate venous incompetence. Results Out of 97 patients (mean age, 37.09±11.59 years; range, 19~69 years), 50 patients (51.5%) had normal findings, 24 patients (24.7%) had arterial insufficiency, 15 patients (15.5%) had a venous leak, and 8 patients (8.2%) patients had arterial insufficiency with a venous leak. Psychogenic erectile dysfunction was significantly higher among patients aged ≤40 years, while arterial insufficiency with or without a venous leak was significantly higher among patients aged >40 years (p=0.022). Conclusions A majority of the studied individuals demonstrated no organic cause of erectile dysfunction, thus confirming a high prevalence of the psychogenic etiology, particularly in relatively young individuals. PMID:28459144

Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia.

PubMed

Fitzgerald, Julie C; Weiss, Scott L; Maude, Shannon L; Barrett, David M; Lacey, Simon F; Melenhorst, J Joseph; Shaw, Pamela; Berg, Robert A; June, Carl H; Porter, David L; Frey, Noelle V; Grupp, Stephan A; Teachey, David T

2017-02-01

Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor-modified T cell therapy. Retrospective cohort study. Academic children's hospital. Thirty-nine subjects with relapsed/refractory acute lymphoblastic leukemia treated with chimeric antigen receptor-modified T cell therapy on a phase I/IIa clinical trial (ClinicalTrials.gov number NCT01626495). All subjects received chimeric antigen receptor-modified T cell therapy. Thirteen subjects with cardiovascular dysfunction were treated with the interleukin-6 receptor antibody tocilizumab. Eighteen subjects (46%) developed grade 3-4 cytokine release syndrome, with prolonged fever (median, 6.5 d), hyperferritinemia (median peak ferritin, 60,214 ng/mL), and organ dysfunction. Fourteen (36%) developed cardiovascular dysfunction treated with vasoactive infusions a median of 5 days after T cell therapy. Six (15%) developed acute respiratory failure treated with invasive mechanical ventilation a median of 6 days after T cell therapy; five met criteria for acute respiratory distress syndrome. Encephalopathy, hepatic, and renal dysfunction manifested later than cardiovascular and respiratory dysfunction. Subjects had a median of 15 organ dysfunction days (interquartile range, 8-20). Treatment with tocilizumab in 13 subjects resulted in rapid defervescence (median, 4 hr) and clinical improvement. Grade 3-4 cytokine release syndrome occurred in 46% of patients following T cell therapy for relapsed/refractory acute lymphoblastic leukemia. Clinicians should be aware of expanding use of this breakthrough therapy and implications for critical care units in cancer centers.

Increased risk of organic erectile dysfunction in patients with chronic fatigue syndrome: a nationwide population-based cohort study.

PubMed

Chao, C-H; Chen, H-J; Wang, H-Y; Li, T-C; Kao, C-H

2015-07-01

Chronic fatigue syndrome (CFS) is a complex disorder characterized by profound and persistent fatigue and several comorbidities. CFS was previously reported to be associated with female sexual dysfunction. We propose that CFS might also be associated with organic erectile dysfunction (organic ED). We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) Research Database. We identified 2156 male patients who were newly diagnosed with CFS between January 1, 2003 and December 31, 2006. After excluding those younger than 20 years and prevalent cases, 1976 patients were subjected to analysis, and 7904 people served as healthy controls. All study subjects were followed up from the index date to the date of organic ED diagnosis, withdrawal from the NHI program, or the end of 2011. Compared with the non-CFS cohort, the incidence density rate of organic ED was 1.88-fold higher than that in the CFS cohort (3.23 vs. 1.73 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.88 (95% CI = 1.26-2.81) when adjusting for sex and comorbidities. The combined impacts of patients with CFS and cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), depression, and anxiety showed a significant by joint association with organic ED risk compared with patients with no CFS and no counterpart comorbidity. The greatest magnitude of adjusted HR of ED for CFS was observed in individuals without any comorbidity (3.87, 1.95-7.66). The incidence of organic ED is higher among males aged 40 years and over for both CFS and non-CFS cohorts. As the number of comorbidity increases, the incidence of organic ED increases in males without CFS. Higher incidence of organic ED was observed in males with CVD, DM, CKD, depression, or anxiety for both CFS and non-CFS cohorts. © 2015 American Society of Andrology and European Academy of Andrology.

Pathophysiology of the Gut and the Microbiome in the Host Response.

PubMed

Lyons, John D; Coopersmith, Craig M

2017-03-01

To describe and summarize the data supporting the gut as the motor driving critical illness and multiple organ dysfunction syndrome presented at the National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015). Summary of workshop keynote presentation. Not applicable. Presented by an expert in the field, the data assessing the role of gastrointestinal dysfunction driving critical illness were described with a focus on identifying knowledge gaps and research priorities. Summary of presentation and discussion supported and supplemented by relevant literature. The understanding of gut dysfunction in critical illness has evolved greatly over time, and the gut is now often considered as the "motor" of critical illness. The association of the gut with critical illness is supported by both animal models and clinical studies. Initially, the association between gut dysfunction and critical illness focused primarily on bacterial translocation into the bloodstream. However, that work has evolved to include other gut-derived products causing distant injury via other routes (e.g., lymphatics). Additionally, alterations in the gut epithelium may be associated with critical illness and influence outcomes. Gut epithelial apoptosis, intestinal hyperpermeability, and perturbations in the intestinal mucus layer have all been associated with critical illness. Finally, there is growing evidence that the intestinal microbiome plays a crucial role in mediating pathology in critical illness. Further research is needed to better understand the role of each of these mechanisms and their contribution to multiple organ dysfunction syndrome in children.

Reduction of Racial Disparities in Prostate Cancer

DTIC Science & Technology

2006-12-01

hyperplasia, interstitial cystitis/chronic pelvic pain, prostatitis, hypogonadism/androgen deficiency, erectile dysfunction , female sexual...socioeconomically diverse, community-based sample of adults aged 30–79 years in Boston, Massachusetts. This report gives estimates from the 2301 men in...survey is designed to estimate the prevalence of symptoms of urological disorders in a multi-ethnic, community-based sample of adults aged 30−79 years

Multi-level comparison of empathy in schizophrenia: an fMRI study of a cartoon task.

PubMed

Lee, Seung Jae; Kang, Do Hyung; Kim, Chi-Won; Gu, Bon Mi; Park, Ji-Young; Choi, Chi-Hoon; Shin, Na Young; Lee, Jong-Min; Kwon, Jun Soo

2010-02-28

Empathy deficits might play a role in social dysfunction in schizophrenia. However, few studies have investigated the neuroanatomical underpinnings of the subcomponents of empathy in schizophrenia. This study investigated the hemodynamic responses to three subcomponents of empathy in patients with schizophrenia (N=15) and healthy volunteers (N=18), performing an empathy cartoon task during functional magnetic resonance imaging. The experiment used a block design with four conditions: cognitive, emotional, and inhibitory empathy, and physical causality control. Data were analyzed by comparing the blood-oxygen-level-dependent (BOLD) signal activation between the two groups. The cognitive empathy condition activated the right temporal pole to a lesser extent in the patient group than in comparison subjects. In the emotional and inhibitory conditions, the patients showed greater activation in the left insula and in the right middle/inferior frontal cortex, respectively. These findings add to our understanding of the impaired empathy in patients with schizophrenia by identifying a multi-level cortical dysfunction that underlies a deficit in each subcomponent of empathy and highlighting the importance of the fronto-temporal cortical network in ability to empathize. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Spatial organization of multi-enzyme biocatalytic cascades.

PubMed

Quin, M B; Wallin, K K; Zhang, G; Schmidt-Dannert, C

2017-05-23

Industrial biocatalysis is an economically attractive option for the production of valuable chemicals. Our repertoire of cheap building blocks and commodity target molecules is vastly enhanced by multi-enzyme biocatalytic cascades. In order to achieve suitable titers in complex novel biocatalytic schemes, spatial organization may become necessary to overcome barriers caused by slow or inhibited enzymes as well as instability of biocatalysts. A number of spatial organization strategies are currently available, which could be integrated in the design of complex cascades. These include fusion proteins, immobilization on solid supports, multi-dimensional scaffolding, and encapsulation within vessels. This review article highlights recent advances in cascade biocatalysis, discusses the role of spatial organization in reaction kinetics, and presents some of the currently employed strategies for spatial organization of multi-enzyme cascades.

Large focal nodular hyperplasia and extrahepatic portosystemic shunt in a male patient: multi-modality imaging features.

PubMed

Kitzing, Yu Xuan; Gallagher, James; Waugh, Richard

2011-10-01

Congenital extrahepatic portocaval shunt is a rare condition that is described mostly in female patients. We report an unusual case of a young adult male patient with type 1 congenital extrahepatic portocaval shunt with associated development of a focal nodular hyperplasia on a background of regenerative nodules. With multi-slice CT utilisation, there is increased detection of portocaval malformation in asymptomatic patients. This congenital variant is clinically significant with associated development of hepatocellular lesions, hepatic dysfunction and/or encephalopathy. © 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.

STAT3 in the systemic inflammation of cancer cachexia.

PubMed

Zimmers, Teresa A; Fishel, Melissa L; Bonetto, Andrea

2016-06-01

Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both pathological and protective functions for STAT3 in other organs during cachexia. STAT3 also contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia and the potential and perils for targeting STAT3 to reduce cachexia and prolong survival in cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Balance of autonomic nervous system in children having signs of endothelial dysfunction, that were born and are domiciled in contaminated territories.

PubMed

Kondrashova, V G; Kolpakov, I E; Vdovenko, V Yu; Leonovych, O S; Lytvynets, O M; Stepanova, E I

2014-09-01

Objective. The study examined the features of functional state of the autonomic nervous system in children having endothelial dysfunction and permanently residing in contaminated areas. Materials and methods. Clinical and instrumental examination of 101 children aged 7-18 years that were born and are domiciled in contaminated territories, including 37 persons with signs of endothelial dysfunction (subgroup IA) and 64 ones with no signs of endothelial dysfunction (IB subgroup) was conducted. The control group being comparable to the subgroups IA and IB by age, gender and clinical examination results included 37 children neither been domiciled in contaminated areas nor were belonging to the contingent of Chornobyl accident survivors. There were 20 apparently healthy children also examined. Results. Due to peculiarities of physiological pathways providing adaptive responses the children having signs of endothelial dysfunction are characterized by a more pronounced dysregulation of autonomous nervous system both in a resting state and under a functional load simulation, and also by a high strain of adaptation pathways. The lack of autonomous support of cardiovascular system is caused by inadequate adaptive responses of both central regulatory bodies (hypothalamus, vasomotor center) and peripheral receptors. Mainly the failure of segmental autonomous (parasympathetic) structures was revealed. The mode of their response to stress in this case corresponds to that in healthy individuals but at a lower functional level. There is a reduced aerobic capacity of the organism by the Robinson index, contributing to low adaptive range to non-specific stress in children being domiciled on contaminated territories including children having the endothelial dysfunction. Conclusions. Endothelial dysfunction was associated with more pronounced manifestations of autonomic dysregulation and reduced aerobic capacity of the organism being the risk factors of development of a range of somatic diseases requiring the development of prevention measures in children permanently residing in contaminated areas. autonomous nervous system balance, endothelial dysfunction, children, Chornobyl accident. V. G. Kondrashova, I. E. Kolpakov, V. Yu. Vdovenko, O. S. Leonovych, O. M. Lytvynets, E. I. Stepanova.

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

PubMed

Goldstein, Brahm; Giroir, Brett; Randolph, Adrienne

2005-01-01

Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. Consensus conference. This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

PubMed

Daiber, Andreas; Münzel, Thomas

2015-10-10

Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

PubMed Central

2015-01-01

Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury.

PubMed

Fani, Filippo; Regolisti, Giuseppe; Delsante, Marco; Cantaluppi, Vincenzo; Castellano, Giuseppe; Gesualdo, Loreto; Villa, Gianluca; Fiaccadori, Enrico

2018-06-01

Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

Staphylococcal toxic shock syndrome: superantigen-mediated enhancement of endotoxin shock and adaptive immune suppression.

PubMed

Kulhankova, Katarina; King, Jessica; Salgado-Pabón, Wilmara

2014-08-01

Infectious diseases caused by Staphylococcus aureus present a significant clinical and public health problem. S. aureus causes some of the most severe hospital-associated and community-acquired illnesses. Specifically, it is the leading cause of infective endocarditis and osteomyelitis, and the second leading cause of sepsis in the USA. While pathogenesis of S. aureus infections is at the center of current research, many questions remain about the mechanisms underlying staphylococcal toxic shock syndrome (TSS) and associated adaptive immune suppression. Both conditions are mediated by staphylococcal superantigens (SAgs)-secreted staphylococcal toxins that are major S. aureus virulence factors. Toxic shock syndrome toxin-1 (TSST-1) is the SAg responsible for almost all menstrual TSS cases in the USA. TSST-1, staphylococcal enterotoxin B and C are also responsible for most cases of non-menstrual TSS. While SAgs mediate all of the hallmark features of TSS, such as fever, rash, hypotension, and multi-organ dysfunction, they are also capable of enhancing the toxic effects of endogenous endotoxin. This interaction appears to be critical in mediating the severity of TSS and related mortality. In addition, interaction between SAgs and the host immune system has been recognized to result in a unique form of adaptive immune suppression, contributing to poor outcomes of S. aureus infections. Utilizing rabbit models of S. aureus infective endocarditis, pneumonia and sepsis, and molecular genetics techniques, we aim to elucidate the mechanisms of SAg and endotoxin synergism in the pathogenesis of TSS, and examine the cellular and molecular mechanisms underlying SAg-mediated immune dysfunction.

Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome.

PubMed

Kernan, Nancy A; Grupp, Stephan; Smith, Angela R; Arai, Sally; Triplett, Brandon; Antin, Joseph H; Lehmann, Leslie; Shore, Tsiporah; Ho, Vincent T; Bunin, Nancy; Iacobelli, Massimo; Liang, Wei; Hume, Robin; Tappe, William; Soiffer, Robert; Richardson, Paul

2018-05-16

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic stem cell transplant (HSCT) conditioning and chemotherapy. Defibrotide is approved for treatment of hepatic VOD/SOS with pulmonary or renal dysfunction [i.e., multi-organ dysfunction (MOD)] after HSCT in the United States and severe VOD/SOS after HSCT in patients aged older than 1 month in the European Union. Defibrotide was available as an investigational drug by an expanded-access treatment programme (T-IND; NCT00628498). In the completed T-IND, the Kaplan-Meier estimated Day +100 survival for 1000 patients with documented defibrotide treatment after HSCT was 58·9% [95% confidence interval (CI), 55·7-61·9%]. Day +100 survival was also analysed by age and MOD status, and post hoc analyses were performed to determine Day +100 survival by transplant type, timing of VOD/SOS onset (≤21 or >21 days) and timing of defibrotide treatment initiation after VOD/SOS diagnosis. Day +100 survival in paediatric patients was 67·9% (95% CI, 63·8-71·6%) and 47·1% (95% CI, 42·3-51·8%) in adults. All patient subgroups without MOD had higher Day +100 survival than those with MOD; earlier defibrotide initiation was also associated with higher Day +100 survival. The safety profile of defibrotide in the completed T-IND study was similar to previous reports. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Retro-peritoneal cooling for kidney preservation from multi-organ cadaver donors.

PubMed

Salazar-Bañuelos, Anastasio; Monroy-Cuadros, Mauricio; Henriquez-Cooper, Hoover

2018-05-01

Minimizing ischemia is paramount in the procurement of kidneys for transplantation. A fast cooling and expeditious removal is ideal to minimize damage from warm ischemia, however, since the removal of kidneys is delayed in cadaver donation until all other organs are harvested, the risk of kidney damage increases due to contact with the warmer soft body tissues. Surgical techniques that expedite organ retrieval were developed to avoid organ damage. We test a modification of Thomas Starzl's improved technique for multi-organ harvesting by interposing an ice bag between the posterior aspect of the kidney and the psoas muscle in a randomized trial with 21 multi-organ cadaver donors. The modified technique decreases the extraction temperature of the kidneys significantly in comparison with the controls, p < .001. This simple technique improves the preservation of kidneys from cadaver donors, and can potentially have more impact on multi-organ donation after cardiac death. Copyright © 2018 Elsevier Inc. All rights reserved.

Automatic abdominal multi-organ segmentation using deep convolutional neural network and time-implicit level sets.

PubMed

Hu, Peijun; Wu, Fa; Peng, Jialin; Bao, Yuanyuan; Chen, Feng; Kong, Dexing

2017-03-01

Multi-organ segmentation from CT images is an essential step for computer-aided diagnosis and surgery planning. However, manual delineation of the organs by radiologists is tedious, time-consuming and poorly reproducible. Therefore, we propose a fully automatic method for the segmentation of multiple organs from three-dimensional abdominal CT images. The proposed method employs deep fully convolutional neural networks (CNNs) for organ detection and segmentation, which is further refined by a time-implicit multi-phase evolution method. Firstly, a 3D CNN is trained to automatically localize and delineate the organs of interest with a probability prediction map. The learned probability map provides both subject-specific spatial priors and initialization for subsequent fine segmentation. Then, for the refinement of the multi-organ segmentation, image intensity models, probability priors as well as a disjoint region constraint are incorporated into an unified energy functional. Finally, a novel time-implicit multi-phase level-set algorithm is utilized to efficiently optimize the proposed energy functional model. Our method has been evaluated on 140 abdominal CT scans for the segmentation of four organs (liver, spleen and both kidneys). With respect to the ground truth, average Dice overlap ratios for the liver, spleen and both kidneys are 96.0, 94.2 and 95.4%, respectively, and average symmetric surface distance is less than 1.3 mm for all the segmented organs. The computation time for a CT volume is 125 s in average. The achieved accuracy compares well to state-of-the-art methods with much higher efficiency. A fully automatic method for multi-organ segmentation from abdominal CT images was developed and evaluated. The results demonstrated its potential in clinical usage with high effectiveness, robustness and efficiency.

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

PubMed

Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

2013-11-28

To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction. Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

Predicting athletes' functional and dysfunctional emotions: The role of the motivational climate and motivation regulations.

PubMed

Ruiz, Montse C; Haapanen, Saara; Tolvanen, Asko; Robazza, Claudio; Duda, Joan L

2017-08-01

This study examined the relationships between perceptions of the motivational climate, motivation regulations, and the intensity and functionality levels of athletes' pleasant and unpleasant emotional states. Specifically, we examined the hypothesised mediational role of motivation regulations in the climate-emotion relationship. We also tested a sequence in which emotions were assumed to be predicted by the motivational climate dimensions and then served as antecedents to variability in motivation regulations. Participants (N = 494) completed a multi-section questionnaire assessing targeted variables. Structural equation modelling (SEM) revealed that a perceived task-involving climate was a positive predictor of autonomous motivation and of the impact of functional anger, and a negative predictor of the intensity of anxiety and dysfunctional anger. Autonomous motivation was a partial mediator of perceptions of a task-involving climate and the impact of functional anger. An ego-involving climate was a positive predictor of controlled motivation, and of the intensity and impact of functional anger and the intensity of dysfunctional anger. Controlled motivation partially mediated the relationship between an ego-involving climate and the intensity of dysfunctional anger. Good fit to the data also emerged for the motivational climate, emotional states, and motivation regulations sequence. Findings provide support for the consideration of hedonic tone and functionality distinctions in the assessment of athletes' emotional states.

Managing Intercultural Teams: The eOrganization Exercise

ERIC Educational Resources Information Center

Humes, Michelle; Reilly, Anne H.

2008-01-01

In today's global environment, intercultural teams may become the most effective teams in an organization when their diversity is managed as an asset. However, because of miscommunication and conflict, intercultural teams often become dysfunctional. This experiential group exercise demonstrates how cultural dimensions such as individualism and…

Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction.

PubMed

Ito, Satomi; Magalska, Adriana; Alcaraz-Iborra, Manuel; Lopez-Atalaya, Jose P; Rovira, Victor; Contreras-Moreira, Bruno; Lipinski, Michal; Olivares, Roman; Martinez-Hernandez, Jose; Ruszczycki, Blazej; Lujan, Rafael; Geijo-Barrientos, Emilio; Wilczynski, Grzegorz M; Barco, Angel

2014-07-18

The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice expressing GFP-tagged histone H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons caused chromocenter declustering and disrupted the association of heterochromatin with the nuclear lamina. The loss of these structures did not affect neuronal viability but was associated with specific transcriptional and behavioural deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D organization of chromatin within neuronal cells provides an additional level of epigenetic regulation of gene expression that critically impacts neuronal function. This in turn suggests that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture.

Multi-electrolyte-step anodic aluminum oxide method for the fabrication of self-organized nanochannel arrays

PubMed Central

2012-01-01

Nanochannel arrays were fabricated by the self-organized multi-electrolyte-step anodic aluminum oxide [AAO] method in this study. The anodization conditions used in the multi-electrolyte-step AAO method included a phosphoric acid solution as the electrolyte and an applied high voltage. There was a change in the phosphoric acid by the oxalic acid solution as the electrolyte and the applied low voltage. This method was used to produce self-organized nanochannel arrays with good regularity and circularity, meaning less power loss and processing time than with the multi-step AAO method. PMID:22333268

77 FR 38766 - Proposed Information Collection; Comment Request; International Client Life-Cycle Multi-Purpose...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... Request; International Client Life-Cycle Multi-Purpose Forms AGENCY: International Trade Administration... aspects of an international organization's life-cycle with CS. CS is mandated by Congress to help U.S... trade events to U.S. organizations. The International Client Life-cycle Multi-Purpose Forms, previously...

7 CFR 205.305 - Multi-ingredient packaged products with less than 70 percent organically produced ingredients.

Code of Federal Regulations, 2011 CFR

2011-01-01

... organically produced ingredients may only identify the organic content of the product by: (1) Identifying each... statement, displaying the product's percentage of organic contents on the information panel. (b... 7 Agriculture 3 2011-01-01 2011-01-01 false Multi-ingredient packaged products with less than 70...

Clinical Predictors of Multiple Organ Dysfunction Syndromes in Pediatric patients with Scrub Typhus.

PubMed

Zhao, Dongying; Zhang, Yongjun; Yin, Zhaoqing; Zhao, Jing; Yang, Defeng; Zhou, Qun

2017-06-01

Scrub typhus can produce multiple organ dysfunction syndrome (MODS). Early recognition of the patients at risk of MODS would be helpful in providing timely management and reducing the mortality. In all, 449 children with scrub typhus were enrolled at three hospitals in Yunnan, China from January 2010 to January 2015. The patients' clinical status of organ system dysfunction was evaluated on the day of discharge from hospital by using standard criteria. The patients were classified into MODS present (64 cases, 14.3%) or MODS absent (385 cases, 85.7%). Multivariate logistic regression analyses revealed that the prognostic factors for MODS included skin rash (odds ratio, OR = 3.3, p = 0.037), time interval form treatment to defervescence (OR = 1.2, p = 0.035), hemoglobin (OR = 0.54, p = 0.041), platelet counts (OR = 0.06, p < 0.001), aspartate-aminotransferase (OR = 4.7, p = 0.011) and total bilirubin (OR = 2.3, p = 0.013). By describing risk factors resulting in MODS in pediatric scrub typhus, our study provides clinicians with important information to improve the clinical monitoring and prognostication of MODS. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Triage of patients with acute gastrointestinal bleeding for intensive care unit admission based on risk factors for poor outcome.

PubMed

Afessa, B

2000-04-01

This study's aim was to determine the prognostic factors and to develop a triage system for intensive care unit (ICU) admission of patients with gastrointestinal bleeding (GIB). This prospective, observational study included 411 adults consecutively hospitalized for GIB. Each patient's selected clinical findings and laboratory values at presentation were obtained. The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated from the initial findings in the emergency department. Poor outcome was defined as recurrent GIB, emergency surgery, or death. The role of hepatic cirrhosis, APACHE II score, active GIB, end-organ dysfunction, and hypotension in predicting outcome was evaluated. Chi-square, Student's t, Mann-Whitney U, and logistic regression analysis tests were used for statistical comparisons. Poor outcome developed in 81 (20%) patients; 39 died, 23 underwent emergency surgery, and 47 rebled. End-organ dysfunction, active bleeding, hepatic cirrhosis, and high APACHE II scores were independent predictors of poor outcome with odds ratios of 3:1, 3:1, 2:3, and 1:1, respectively. The ICU admission rate was 37%. High APACHE II score, active bleeding, end-organ dysfunction, and hepatic cirrhosis are independent predictors of poor outcome in patients with GIB and can be used in the triage of these patients for ICU admission.

Mitochondrial Dysfunction in Lysosomal Storage Disorders

PubMed Central

de la Mata, Mario; Cotán, David; Villanueva-Paz, Marina; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan M.; Tiscornia, Gustavo; Oropesa-Ávila, Manuel

2016-01-01

Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs. PMID:28933411

Cardiovascular risk reduction by reversing endothelial dysfunction:ARBs, ACE inhibitors, or both? Expectations from The ONTARGET Trial Programme

PubMed Central

Ruilope, Luis Miguel; Redón, Josep; Schmieder, Roland

2007-01-01

Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008. PMID:17583170

Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction.

PubMed

Murphy, Laura S; Wickersham, Nancy; McNeil, J Brennan; Shaver, Ciara M; May, Addison K; Bastarache, Julie A; Ware, Lorraine B

2017-10-06

Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

High-volume plasma exchange in a patient with acute liver failure due to non-exertional heat stroke in a sauna.

PubMed

Chen, Kuan-Jung; Chen, Tso-Hsiao; Sue, Yuh-Mou; Chen, Tzay-Jinn; Cheng, Chung-Yi

2014-10-01

Heat stroke is a life-threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non-exercise-induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non-exercise-induced heat stroke in a 73-year-old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high-volume plasma exchange, and the patient recovered completely after treatment. © 2014 Wiley Periodicals, Inc.

The Role of Pay Satisfaction in Instructor Satisfaction

ERIC Educational Resources Information Center

Wilson, Jackson

2009-01-01

Voluntary employee turnover is a major factor affecting adventure education (AE) organizations (Garret, 2003). Voluntary turnover often is dysfunctional for both employees and organizations (Birmingham, 1989; Podsakoff, LePine, & LePine, 2007). Turnover can result in increased employee and organizational costs (e.g., McKinney, Bartlett, &…

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy.

PubMed

Marasco, Silvana F; Lo, Casey; Murphy, Deirdre; Summerhayes, Robyn; Quayle, Margaret; Zimmet, Adam; Bailey, Michael

2016-01-01

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long-term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge-to-bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end-organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous-flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty-three patients required ECLS support pre-LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end-organ function pre-VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end-organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these "crash and burn" patients. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The impact of extracerebral organ failure on outcome of patients after cardiac arrest: an observational study from the ICON database.

PubMed

Nobile, Leda; Taccone, Fabio S; Szakmany, Tamas; Sakr, Yasser; Jakob, Stephan M; Pellis, Tommaso; Antonelli, Massimo; Leone, Marc; Wittebole, Xavier; Pickkers, Peter; Vincent, Jean-Louis

2016-11-14

We used data from a large international database to assess the incidence and impact of extracerebral organ dysfunction on prognosis of patients admitted after cardiac arrest (CA). This was a sub-analysis of the Intensive Care Over Nations (ICON) database, which contains data from all adult patients admitted to one of 730 participating intensive care units (ICUs) in 84 countries from 8-18 May 2012, except admissions for routine postoperative surveillance. For this analysis, patients admitted after CA (defined as those with "post-anoxic coma" or "cardiac arrest" as the reason for ICU admission) were included. Data were collected daily in the ICU for a maximum of 28 days; patients were followed up for outcome data until death, hospital discharge, or a maximum of 60 days in-hospital. Favorable neurological outcome was defined as alive at hospital discharge with a last available neurological Sequential Organ Failure Assessment (SOFA) subscore of 0-2. Among the 469 patients admitted after CA, 250 (53 %) had had out-of-hospital CA; 210 (45 %) patients died in the ICU and 357 (76 %) had an unfavorable neurological outcome. Non-survivors had a higher incidence of renal (43 vs. 16 %), cardiovascular (56 vs. 45 %), and respiratory (62 vs. 48 %) failure on admission and during the ICU stay than survivors (all p < 0.05). Similar results were found for patients with unfavorable vs. favorable neurological outcomes. In multivariable analysis, independent predictors of ICU mortality were renal failure on admission, high admission Simplified Acute Physiology Score (SAPS) II, high maximum serum lactate levels within the first 24 h after ICU admission, and development of sepsis. Independent predictors of unfavorable neurological outcome were mechanical ventilation on admission, high admission SAPS II score, and neurological dysfunction on admission. In this multicenter cohort, extracerebral organ dysfunction was common in CA patients. Renal failure on admission was the only extracerebral organ dysfunction independently associated with higher ICU mortality.

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

PubMed

Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

2010-01-01

Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days. In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables.

Portal, superior mesenteric and splenic vein thrombosis secondary to hyperhomocysteinemia with pernicious anemia: a case report.

PubMed

Venkatesh, Prashanth; Shaikh, Nissar; Malmstrom, Mohammad F; Kumar, Vajjala R; Nour, Bakr

2014-08-25

Acute portomesenteric vein thrombosis is an uncommon but serious condition with potential sequelae, such as small-bowel gangrene and end-stage hepatic failure. It is known to be caused by various pro-thrombotic states, including hyperhomocysteinemia. We describe what is, to the best of our knowledge, the first reported case of concomitant thrombosis of portal, superior mesenteric and splenic veins due to hyperhomocysteinemia secondary to pernicious anemia and no other risk factors. A 60-year-old Indian man presented with epigastric pain, diarrhea and vomiting. An abdominal imaging scan showed that he had concomitant pernicious anemia and concomitant portal, superior mesenteric and splenic vein thrombosis. A work-up for the patient's hypercoagulable state revealed hyperhomocysteinemia, an undetectable vitamin B12 level and pernicious anemia with no other thrombophilic state. He developed infarction with perforation of the small bowel and subsequent septic shock with multi-organ dysfunction syndrome, and he ultimately died due to progressive hepatic failure. This report demonstrates that pernicious anemia, on its own, can lead to hyperhomocysteinemia significant enough to lead to lethal multiple splanchnic vein thrombosis. Our case also underscores the need to (1) consider portomesenteric thrombosis in the differential diagnosis of epigastric abdominal pain, (2) perform a complete thrombotic work-up to elucidate metabolic abnormalities that could be contributing to a pro-thrombotic state and (3) initiate aggressive measures, including early consideration of multi-visceral transplantation, in order to avoid decompensation and a significant adverse outcome.

Nephrotoxicity of Natural Products.

PubMed

Nauffal, Mary; Gabardi, Steven

2016-01-01

The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education. © 2016 S. Karger AG, Basel.

Parental and Family Factors as Predictors of Threat Bias in Anxious Youth

PubMed Central

Blossom, Jennifer B.; Ginsburg, Golda S.; Birmaher, Boris; Walkup, John T.; Kendall, Philip C.; Keeton, Courtney P.; Langley, Audra K.; Piacentini, John C.; Sakolsky, Dara; Albano, Anne Marie

2014-01-01

The present study examined the relative predictive value of parental anxiety, parents' expectation of child threat bias, and family dysfunction on child's threat bias in a clinical sample of anxious youth. Participants (N = 488) were part of the Child/Adolescent Anxiety Multi-modal study (CAMS), ages 7–17 years (M = 10.69; SD = 2.80). Children met diagnostic criteria for generalized anxiety disorder, separation anxiety and/or social phobia. Children and caregivers completed questionnaires assessing child threat bias, child anxiety, parent anxiety and family functioning. Child age, child anxiety, parental anxiety, parents' expectation of child's threat bias and child-reported family dysfunction were significantly associated with child threat bias. Controlling for child's age and anxiety, regression analyses indicated that parents' expectation of child's threat bias and child-reported family dysfunction were significant positive predictors of child's self-reported threat bias. Findings build on previous literature by clarifying parent and family factors that appear to play a role in the development or maintenance of threat bias and may inform etiological models of child anxiety. PMID:25328258

Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

PubMed Central

Mantena, Sudheer K; King, Adrienne L; Andringa, Kelly K; Landar, Aimee; Darley-Usmar, Victor; Bailey, Shannon M

2007-01-01

Mitochondrial dysfunction is known to be a contributing factor to a number of diseases including chronic alcohol induced liver injury. While there is a detailed understanding of the metabolic pathways and proteins of the liver mitochondrion, little is known regarding how changes in the mitochondrial proteome may contribute to the development of hepatic pathologies. Emerging evidence indicates that reactive oxygen and nitrogen species disrupt mitochondrial function through post-translational modifications to the mitochondrial proteome. Indeed, various new affinity labeling reagents are available to test the hypothesis that post-translational modification of proteins by reactive species contributes to mitochondrial dysfunction and alcoholic fatty liver disease. Specialized proteomic techniques are also now available, which allow for identification of defects in the assembly of multi-protein complexes in mitochondria and the resolution of the highly hydrophobic proteins of the inner membrane. In this review knowledge gained from the study of changes to the mitochondrial proteome in alcoholic hepatotoxicity will be described and placed into a mechanistic framework to increase understanding of the role of mitochondrial dysfunction in liver disease. PMID:17854139

A mathematical model for active contraction in healthy and failing myocytes and left ventricles.

PubMed

Cai, Li; Wang, Yongheng; Gao, Hao; Li, Yiqiang; Luo, Xiaoyu

2017-01-01

Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV). The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model. We first studied the electro-mechanics coupling in a single myocyte in the healthy and diseased left ventricle, and then the single cell model was embedded in a dynamic LV model to investigate the compensation mechanism of LV pump function due to myocardial dysfunction caused by abnormality in cellular calcium dynamics. The multi-scale LV model was solved using an in-house developed hybrid immersed boundary method with finite element extension. The predictions of the healthy LV model agreed well with the clinical measurements and other studies, and likewise, the results in the failing states were also consistent with clinical observations. In particular, we found that a low level of intracellular Ca2+ transient in myocytes can result in LV pump function failure even with increased myocardial contractility, decreased systolic blood pressure, and increased diastolic filling pressure, even though they will increase LV stroke volume. Our work suggested that treatments targeted at increased contractility and lowering the systolic blood pressure alone are not sufficient in preventing LV pump dysfunction, restoring a balanced physiological Ca2+ handling mechanism is necessary.

Vitamin C: The next step in sepsis management?

PubMed

Teng, J; Pourmand, A; Mazer-Amirshahi, M

2018-02-01

Sepsis is a life-threatening medical condition, affecting approximately 26 million people worldwide every year. The disease is a continuum, marked by dysregulated inflammation and hemodynamic instability leading to shock, multi-system organ dysfunction, and death. Over the past decades, there has been a focus on the early identification and treatment of sepsis primarily with bundled and goal directed therapy. Despite these advances, morbidity and mortality has remained high, prompting investigation into novel therapies. Vitamin C is a water-soluble vitamin that plays a role in mediating inflammation through antioxidant activities and is also important in the synthesis of cortisol, catecholamines, and vasopressin, which are key mediators in the disease process. Emerging evidence provides cursory data in support of the administration of vitamin C in addition to standard therapy to ameliorate the effects of inflammation and improve hemodynamic stability in patients with sepsis and septic shock; however, further evidence is needed to support this practice. This review discusses the physiologic role of vitamin C as well as the recent literature and evidence for the use of vitamin C in patients presenting with sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder.

PubMed

Ogier de Baulny, Hélène; Schiff, Manuel; Dionisi-Vici, Carlo

2012-05-01

Lysinuric protein intolerance (LPI) is an inherited defect of cationic amino acid (lysine, arginine and ornithine) transport at the basolateral membrane of intestinal and renal tubular cells caused by mutations in SLC7A7 encoding the y(+)LAT1 protein. LPI has long been considered a relatively benign urea cycle disease, when appropriately treated with low-protein diet and l-citrulline supplementation. However, the severe clinical course of this disorder suggests that LPI should be regarded as a severe multisystem disease with uncertain outcome. Specifically, immune dysfunction potentially attributable to nitric oxide (NO) overproduction secondary to arginine intracellular trapping (due to defective efflux from the cell) might be a crucial pathophysiological route explaining many of LPI complications. The latter comprise severe lung disease with pulmonary alveolar proteinosis, renal disease, hemophagocytic lymphohistiocytosis with subsequent activation of macrophages, various auto-immune disorders and an incompletely characterized immune deficiency. These results have several therapeutic implications, among which lowering the l-citrulline dosage may be crucial, as excessive citrulline may worsen intracellular arginine accumulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Kidney-on-a-Chip: a New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

PubMed

Lee, Jeonghwan; Kim, Sejoong

2018-03-08

The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. A kidney-on-a-chip is a microfluidic device that allows the culture of living renal cells in 3-dimensional channels and mimics the human microphysiological environment, thus simulating the actual drug filtering, absorption, and secretion process.. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. We focus on pharmacological interactions and drug-induced nephrotoxicity, and additionally discuss the development of multi-organ chips and their possible applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Prefrontal system dysfunction and credit card debt.

PubMed

Spinella, Marcello; Yang, Bijou; Lester, David

2004-10-01

Credit card use often involves a disadvantageous allocation of finances because they allow for spending beyond means and buying on impulse. Accordingly they are associated with increased bankruptcy, anxiety, stress, and health problems. Mounting evidence from functional neuroimaging and clinical studies implicates prefrontal-subcortical systems in processing financial information. This study examined the relationship of credit card debt and executive functions using the Frontal System Behavior Scale (FRSBE). After removing the influences of demographic variables (age, sex, education, and income), credit card debt was associated with the Executive Dysfunction scale, but not the Apathy or Disinhibition scales. This suggests that processes of conceptualizing and organizing finances are most relevant to credit card debt, and implicates dorsolateral prefrontal dysfunction.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: from molecular genetics to clinical features.

PubMed

Zhou, Yaoyao; Zhang, Junfeng

2014-09-20

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare but fatal autosomal recessive multisystem disorder caused by mutations in the VPS33B or VIPAR gene. The classical presentation of ARC includes congenital joint contractures, renal tubular dysfunction, and cholestasis. Additional features include ichthyosis, central nervous system malformation, platelet anomalies, and severe failure to thrive. Diagnosis of ARC syndrome relies on clinical features, organ biopsy, and mutational analysis. However, no specific treatment currently exists for this syndrome. This is an overview of the latest knowledge regarding the genetic features and clinical manifestations of ARC syndrome. Greater awareness and understanding of this syndrome should allow more timely intervention with potential for improving long-term outcome.

Construction of multi-scale consistent brain networks: methods and applications.

PubMed

Ge, Bao; Tian, Yin; Hu, Xintao; Chen, Hanbo; Zhu, Dajiang; Zhang, Tuo; Han, Junwei; Guo, Lei; Liu, Tianming

2015-01-01

Mapping human brain networks provides a basis for studying brain function and dysfunction, and thus has gained significant interest in recent years. However, modeling human brain networks still faces several challenges including constructing networks at multiple spatial scales and finding common corresponding networks across individuals. As a consequence, many previous methods were designed for a single resolution or scale of brain network, though the brain networks are multi-scale in nature. To address this problem, this paper presents a novel approach to constructing multi-scale common structural brain networks from DTI data via an improved multi-scale spectral clustering applied on our recently developed and validated DICCCOLs (Dense Individualized and Common Connectivity-based Cortical Landmarks). Since the DICCCOL landmarks possess intrinsic structural correspondences across individuals and populations, we employed the multi-scale spectral clustering algorithm to group the DICCCOL landmarks and their connections into sub-networks, meanwhile preserving the intrinsically-established correspondences across multiple scales. Experimental results demonstrated that the proposed method can generate multi-scale consistent and common structural brain networks across subjects, and its reproducibility has been verified by multiple independent datasets. As an application, these multi-scale networks were used to guide the clustering of multi-scale fiber bundles and to compare the fiber integrity in schizophrenia and healthy controls. In general, our methods offer a novel and effective framework for brain network modeling and tract-based analysis of DTI data.

Emergency management of fat embolism syndrome

PubMed Central

Shaikh, Nissar

2009-01-01

Fat emboli occur in all patients with long-bone fractures, but only few patients develop systemic dysfunction, particularly the triad of skin, brain, and lung dysfunction known as the fat embolism syndrome (FES). Here we review the FES literature under different subheadings. The incidence of FES varies from 1–29%. The etiology may be traumatic or, rarely, nontraumatic. Various factors increase the incidence of FES. Mechanical and biochemical theories have been proposed for the pathophysiology of FES. The clinical manifestations include respiratory and cerebral dysfunction and a petechial rash. Diagnosis of FES is difficult. The other causes for the above-mentioned organ dysfunction have to be excluded. The clinical criteria along with imaging studies help in diagnosis. FES can be detected early by continuous pulse oximetry in high-risk patients. Treatment of FES is essentially supportive. Medications, including steroids, heparin, alcohol, and dextran, have been found to be ineffective. PMID:19561953

Strategies to reverse endothelial progenitor cell dysfunction in diabetes.

PubMed

Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo

2012-01-01

Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue

PubMed Central

Pérez, Laura M.; Pareja‐Galeano, Helios; Sanchis‐Gomar, Fabián; Emanuele, Enzo; Lucia, Alejandro

2016-01-01

Abstract The increasing ageing of our societies is accompanied by a pandemic of obesity and related cardiometabolic disorders. Progressive dysfunction of the white adipose tissue is increasingly recognized as an important hallmark of the ageing process, which in turn contributes to metabolic alterations, multi‐organ damage and a systemic pro‐inflammatory state (‘inflammageing’). On the other hand, obesity, the paradigm of adipose tissue dysfunction, shares numerous biological similarities with the normal ageing process such as chronic inflammation and multi‐system alterations. Accordingly, understanding the interplay between accelerated ageing related to obesity and adipose tissue dysfunction is critical to gain insight into the ageing process in general as well as into the pathophysiology of obesity and other related conditions. Here we postulate the concept of ‘adipaging’ to illustrate the common links between ageing and obesity and the fact that, to a great extent, obese adults are prematurely aged individuals. PMID:26926488

Are Emotions Transmitted From Work to Family? A Crossover Model of Psychological Contract Breach.

PubMed

Liang, Huai-Liang

2018-01-01

Based on affective events theory and the crossover model, this study examines the effect of psychological contract breach on employee dysfunctional behavior and partner family undermining and explores the crossover effect of employee dysfunctional behavior on partner family undermining in work-family issues. This study collected 370 employee-partner dyads (277 male employees, 93 female employees, M age = 43.59 years) from a large manufacturing organization. The results of this study support the conception that employees' psychological contract breach results in frustration in the workplace. In addition, mediation analysis results reveal that psychological contract breach relates to employee dysfunctional behavior in the workplace. The findings show that partners' psychological strain mediates the relationship between employee dysfunctional behavior and partner family undermining. Furthermore, these findings provide investigations for the crossover model to display the value of psychological contract breach in family issues.

Hybrid Revascularization for Critical Limb Ischemia Triggered by Multiple Organ Dysfunction Due to Acute Pneumonia; Urgent Catheter Intervention Followed by Low-Density-Lipoprotein Apheresis and Elective Peripheral Bypass Surgery

PubMed Central

2014-01-01

A 66-year-old man was referred for treatment of critical limb ischemia arising with multiple organ dysfunction due to acute pneumonia. Angiographic examinations demonstrated total obstruction of the bilateral external iliac arteries and the bilateral superficial femoral arteries with collateral circulation to the distal vessels. Urgent percutaneous transluminal angioplasty dissolved the obstruction of the left external iliac artery, and subsequent low-density-lipoprotein apheresis ameliorated his progressive ischemia in the lower extremities. Femoro-femoral and bilateral femoro-popliteal bypasses were performed 31 days after the endovascular intervention, which achieved successful limb salvage with the relief of ischemic symptoms related to arteriosclerotic obliterans. PMID:24995063

Pharmacological Management of Cardiorenal Syndromes

PubMed Central

House, Andrew A.; Haapio, Mikko; Lassus, Johan; Bellomo, Rinaldo; Ronco, Claudio

2011-01-01

Cardiorenal syndromes are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The pharmacological management of Cardiorenal syndromes may be complicated by unanticipated or unintended effects of agents targeting one organ on the other. Hence, a thorough understanding of the pathophysiology of these disorders is paramount. The treatment of cardiovascular diseases and risk factors may affect renal function and modify the progression of renal injury. Likewise, management of renal disease and associated complications can influence heart function or influence cardiovascular risk. In this paper, an overview of pharmacological management of acute and chronic Cardiorenal Syndromes is presented, and the need for high-quality future studies in this field is highlighted. PMID:21660311

How does healthy aging impact on the circadian clock?

PubMed

Popa-Wagner, Aurel; Buga, Ana-Maria; Dumitrascu, Dinu Iuliu; Uzoni, Adriana; Thome, Johannes; Coogan, Andrew N

2017-02-01

Circadian rhythms are recurring patterns in a host of physiological and other parameters that recur with periods of near 24 h. These rhythms reflect the temporal organization of an organism's homeostatic control systems and as such are key processes in ensuring optimal physiological performance. Dysfunction of circadian processes is linked with adverse health conditions. In this review we highlight the evidence that normal, healthy aging is associated with changes in the circadian system; we examine the molecular mechanisms through which such changes may arise, discuss whether more robust circadian function is a predictor of longevity and highlight the role of circadian rhythms in age-related diseases. Overall, the literature shows that aging is associated with marked changes in circadian processes, both at the behavioral and molecular levels, and the molecular mechanisms through which such changes arise remain to be elucidated, but may involve inflammatory process, redox homeostasis and epigenetic modifications. Understanding the nature of age-related circadian dysfunction will allow for the design of chronotherapeutic intervention strategies to attenuate circadian dysfunction and thus improve health and quality of life.

Sex differences in baroreflex sensitivity, heart rate variability, and end organ damage in the TGR(mRen2)27 rat.

PubMed

Johnson, Megan S; DeMarco, Vincent G; Heesch, Cheryl M; Whaley-Connell, Adam T; Schneider, Rebecca I; Rehmer, Nathan T; Tilmon, Roger D; Ferrario, Carlos M; Sowers, James R

2011-10-01

The aim of this investigation was to evaluate sex differences in baroreflex and heart rate variability (HRV) dysfunction and indexes of end-organ damage in the TG(mRen2)27 (Ren2) rat, a model of renin overexpression and tissue renin-angiotensin-aldosterone system overactivation. Blood pressure (via telemetric monitoring), blood pressure variability [BPV; SD of systolic blood pressure (SBP)], spontaneous baroreflex sensitivity, HRV [HRV Triangular Index (HRV-TI), standard deviation of the average NN interval (SDNN), low and high frequency power (LF and HF, respectively), and Poincaré plot analysis (SD1, SD2)], and cardiovascular function (pressure-volume loop analysis and proteinuria) were evaluated in male and female 10-wk-old Ren2 and Sprague Dawley rats. The severity of hypertension was greater in Ren2 males (R2-M) than in Ren2 females (R2-F). Increased BPV, suppression of baroreflex gain, decreased HRV, and associated end-organ damage manifested as cardiac dysfunction, myocardial remodeling, elevated proteinuria, and tissue oxidative stress were more pronounced in R2-M compared with R2-F. During the dark cycle, HRV-TI and SDNN were negatively correlated with SBP within R2-M and positively correlated within R2-F; within R2-M, these indexes were also negatively correlated with end-organ damage [left ventricular hypertrophy (LVH)]. Furthermore, within R2-M only, LVH was strongly correlated with indexes of HRV representing predominantly vagal (HF, SD1), but not sympathetic (LF, SD2), variability. These data demonstrated relative protection in females from autonomic dysfunction and end-organ damage associated with elevated blood pressure in the Ren2 model of hypertension.

Predicting the severity of systemic inflammatory response syndrome (SIRS)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers.

PubMed

Iba, Toshiaki; Gando, Satoshi; Murata, Atsuo; Kushimoto, Shigeki; Saitoh, Daizoh; Eguchi, Yutaka; Ohtomo, Yasuhiro; Okamoto, Kohji; Koseki, Kazuhide; Mayumi, Toshihiko; Ikeda, Toshiaki; Ishhikura, Hiroyasu; Ueyama, Masashi; Ogura, Yuji; Endo, Shigeatsu; Shimazaki, Shuji

2007-11-01

The changes in biomarkers of coagulation or fibrinolysis, anticoagulation, inflammation, and endothelial damage occur in patients with systemic inflammatory response syndrome (SIRS). The purpose of this study is to assess the prognostic value of these markers in patients with SIRS-associated hypercoagulopathy. Sixty-six SIRS patients with a platelet count less than 15.0 x 10(4)/mm3 in three university hospital intensive care units were enrolled in this prospective, comparative study. Blood samples were obtained on day 0 and day 2. Twelve hemostatic, inflammatory, and vascular endothelial indices were measured and the data were compared between the severe group (patients with a total maximum Sequential Organ Failure Assessment score of 10 or more and nonsurvivors; n = 25) and the less-severe group (Sequential Organ Failure Assessment score <10; n = 41). Significant changes between the groups were observed in platelet count, fibrin or fibrinogen degradation products, interleukin-6, soluble thrombomodulin, antithrombin (AT) activity, and protein C activity, both on day 0 and on day 2. In contrast, the d-dimer, soluble fibrin, plasmin-[alpha]2-antiplasmin complex, and E-selectin levels were higher in the severe group only on day 2. No significant difference was seen regarding the thrombin-AT complex and total plasminogen activator inhibitor on both days. A comparison of the areas under the receiver operating characteristic curve revealed the AT activity to be the best predictor of a progression of organ dysfunction. The changes in some hemostatic molecular markers and vascular endothelial markers were conspicuous in patients with organ dysfunction. The AT activity is considered to be the most useful predictor of organ dysfunction.

The Role of Somatic Symptoms in Sexual Medicine: Somatization as Important Contextual Factor in Male Sexual Dysfunction.

PubMed

Fanni, Egidia; Castellini, Giovanni; Corona, Giovanni; Boddi, Valentina; Ricca, Valdo; Rastrelli, Giulia; Fisher, Alessandra Daphne; Cipriani, Sarah; Maggi, Mario

2016-09-01

An important feature of somatic symptom disorder is the subjective perception of the physical symptoms and its maladaptive interpretation. Considering that psychological distress is often expressed through somatic symptoms, it is possible that they underlie at least a part of the symptoms in subjects complaining of sexual dysfunction. Nevertheless, studies on the impact of somatoform disorders in sexual dysfunction are scanty. To define the psychological, relational, and organic correlates of somatic symptoms in a large sample of patients complaining of sexual problems. A consecutive series of 2833 men (mean age 50.2 ± 13.5 years) was retrospectively studied. Somatic symptoms were assessed using the "somatized anxiety symptoms" subscale of the Middlesex Hospital Questionnaire (MHQ-S). Several clinical, biochemical, psychological, and relational parameters were studied. Patients were interviewed with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). Among the 2833 patients studied, subjects scoring higher on somatic symptoms were older, more obese, reporting unhealthy lifestyle (current smoking, alcohol consumption), and a lower education (all P < .05). Moreover, they reported a general impairment of their sexuality more often, including erectile problems (spontaneous or sexual-related), low sexual desire, decreased frequency of intercourse, and perceived reduction of ejaculate volume (all P < .005). Interestingly, we observed a significant association between MHQ-S scoring with a reduced testosterone level and hypogonadism symptoms (both P < .05). Finally, we found a significant association between somatic symptoms and both SIEDY Scales 1 (organic domain of ED) and 3 (intrapsychic domain of ED) (both P < .0001). The present study demonstrates that the presence of somatic symptoms can represent an important contextual factor in the determination of or in the exacerbation of male sexual dysfunction. High levels of somatic symptoms in subjects with sexual dysfunction can be related to the sexual symptom itself. The consequences of this pattern have great clinical relevance in a sexual medicine setting, considering their severe impact on sexuality. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Aging as an Epigenetic Phenomenon

PubMed Central

Ashapkin, Vasily V.; Kutueva, Lyudmila I.; Vanyushin, Boris F.

2017-01-01

Introduction: Hypermethylation of genes associated with promoter CpG islands, and hypomethylation of CpG poor genes, repeat sequences, transposable elements and intergenic genome sections occur during aging in mammals. Methylation levels of certain CpG sites display strict correlation to age and could be used as “epigenetic clock” to predict biological age. Multi-substrate deacetylases SIRT1 and SIRT6 affect aging via locus-specific modulations of chromatin structure and activity of multiple regulatory proteins involved in aging. Random errors in DNA methylation and other epigenetic marks during aging increase the transcriptional noise, and thus lead to enhanced phenotypic variation between cells of the same tissue. Such variation could cause progressive organ dysfunction observed in aged individuals. Multiple experimental data show that induction of NF-κB regulated gene sets occurs in various tissues of aged mammals. Upregulation of multiple miRNAs occurs at mid age leading to downregulation of enzymes and regulatory proteins involved in basic cellular functions, such as DNA repair, oxidative phosphorylation, intermediate metabolism, and others. Conclusion: Strong evidence shows that all epigenetic systems contribute to the lifespan control in various organisms. Similar to other cell systems, epigenome is prone to gradual degradation due to the genome damage, stressful agents, and other aging factors. But unlike mutations and other kinds of the genome damage, age-related epigenetic changes could be fully or partially reversed to a “young” state. PMID:29081695

Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.

PubMed

Choudhury, Soumen; Kandasamy, Kannan; Maruti, Bhojane Somnath; Addison, M Pule; Kasa, Jaya Kiran; Darzi, Sazad A; Singh, Thakur Uttam; Parida, Subhashree; Dash, Jeevan Ranjan; Singh, Vishakha; Mishra, Santosh Kumar

2015-10-15

Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1β and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

Curcumin Nanoparticle Therapy for Gulf War Illness

DTIC Science & Technology

2017-10-01

13 4 1. INTRODUCTION Gulf war illness (GWI) is a chronic multi-symptom health problem, which afflicts ~30% of veterans who...served in the Persian Gulf War-1 (PGW-1). Brain dysfunction, typified by cognitive, memory and mood impairments, is one of the major health issues in...insects/ticks. The measures included the use of pesticides for the area protection and insect repellants on the skin and uniforms. The pesticides

Progression of Coronary Artery Calcium and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Bakhshi, Hooman; Ambale-Venkatesh, Bharath; Yang, Xiaoying; Ostovaneh, Mohammad R; Wu, Colin O; Budoff, Matthew; Bahrami, Hossein; Wong, Nathan D; Bluemke, David A; Lima, João A C

2017-04-20

Although the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi-Ethnic Study of Atherosclerosis. The Multi-Ethnic Study of Atherosclerosis is a population-based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi-Ethnic Study of Atherosclerosis participants who had baseline and follow-up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2 years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow-up of 9.6 (interquartile range: 8.8-10.6) years, 182 participants developed incident HF. CAC progression of 10 units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease ( P =0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (β=0.16; P =0.03) and LV end systolic volume (β=0.12; P =0.006) after excluding participants with any coronary heart disease. CAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow-up exam independent of overt coronary heart disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Improving sexual health in men with prostate cancer: randomised controlled trial of exercise and psychosexual therapies

PubMed Central

2014-01-01

Background Despite being a critical survivorship care issue, there is a clear gap in current knowledge of the optimal treatment of sexual dysfunction in men with prostate cancer. There is sound theoretical rationale and emerging evidence that exercise may be an innovative therapy to counteract sexual dysfunction in men with prostate cancer. Furthermore, despite the multidimensional aetiology of sexual dysfunction, there is a paucity of research investigating the efficacy of integrated treatment models. Therefore, the purpose of this study is to: 1) examine the efficacy of exercise as a therapy to aid in the management of sexual dysfunction in men with prostate cancer; 2) determine if combining exercise and brief psychosexual intervention results in more pronounced improvements in sexual health; and 3) assess if any benefit of exercise and psychosexual intervention on sexual dysfunction is sustained long term. Methods/Design A three-arm, multi-site randomised controlled trial involving 240 prostate cancer survivors will be implemented. Participants will be randomised to: 1) ‘Exercise’ intervention; 2) ‘Exercise + Psychosexual’ intervention; or 3) ‘Usual Care’. The Exercise group will receive a 6-month, group based, supervised resistance and aerobic exercise intervention. The Exercise + Psychosexual group will receive the same exercise intervention plus a brief psychosexual self-management intervention that addresses psychological and sexual well-being. The Usual Care group will maintain standard care for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (post-intervention) and 1 year follow-up. The primary endpoint is sexual health and secondary endpoints include key factors associated with sexual health in men with prostate cancer. Discussion Sexual dysfunction is one of the most prevalent and distressing consequences of prostate cancer. Despite this, very little is known about the management of sexual dysfunction and current health care services do not adequately meet sexual health needs of survivors. This project will examine the potential role of exercise in the management of sexual dysfunction and evaluate a potential best-practice management approach by integrating pharmacological, physiological and psychological treatment modalities to address the complex and multifaceted aetiology of sexual dysfunction following cancer. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001179729. PMID:24641777

Consideration of sleep dysfunction in rehabilitation.

PubMed

Valenza, Marie Carmen; Rodenstein, Daniel O; Fernández-de-las-Peñas, César

2011-07-01

The physiology of sleep is not completely understood but it is widely accepted that sleep is important to the human body in the recovery of metabolic and neurological processes. This paper summarizes the effects of sleep dysfunction on different systems and considers implications in the context of rehabilitation. When sleep is experimentally completely or partially curtailed important brain functions are impacted leading to psychological and neurological disturbances. Increased cortisol levels, reduction of glucose tolerance, and increased sympathetic nervous system activity have also been identified in healthy subjects under such conditions. Several studies show that 50-80% of patients with chronic pain suffer from sleep dysfunction. It has been suggested that on the one hand pain can cause sleep dysfunction and on the other hand that sleep dysfunction can aggravate pain. The physiologic mechanism behind this interaction is not completely clear; although most authors describe the relationship between pain and sleep dysfunction as aberrant processing of tactile-cutaneous sensory inputs at the meso-encephalic level and in the trigeminal nucleus both when asleep and awake. Decreased duration of sleep also increases heart rate, blood pressure and sympathetic activity magnifying the individual's response to stressful stimuli. Possible causal mechanisms for the established connection between short sleep cycles and coronary pathology include sympathetic nervous system hyperactivity, increased blood pressure increase or reduced glucose tolerance. Finally, sleep and fatigue have traditionally been linked. Fatigue can have a physical etiology but is also associated with depression. Sleep alterations are also considered an important risk factor for psychological dysfunction and also mental illness. However, despite the noted repercussions of sleep dysfunction, studies investigating interventions to improve sleep have been limited in number. Benefits of exercise programs on sleep habits have been controversial with some have finding positive effects, whereas others did not find any significant effect. It is possible that the dose or intensity of exercise programs may have an important influence in the outcomes. It is our opinion that based on the multi-system repercussions of different sleep dysfunctions, evaluation of sleep habits should be considered fundamental in the context of rehabilitation and should be included as part of the clinical history of each patient attending physical therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

Abdominal massage for neurogenic bowel dysfunction in people with multiple sclerosis (AMBER - Abdominal Massage for Bowel Dysfunction Effectiveness Research): study protocol for a randomised controlled trial.

PubMed

McClurg, Doreen; Goodman, Kirsteen; Hagen, Suzanne; Harris, Fional; Treweek, Sean; Emmanuel, Anton; Norton, Christine; Coggrave, Maureen; Doran, Selina; Norrie, John; Donnan, Peter; Mason, Helen; Manoukian, Sarkis

2017-03-29

Multiple sclerosis (MS) is a life-long condition primarily affecting younger adults. Neurogenic bowel dysfunction (NBD) occurs in 50-80% of these patients and is the term used to describe constipation and faecal incontinence, which often co-exist. Data from a pilot study suggested feasibility of using abdominal massage for the relief of constipation, but the effectiveness remains uncertain. This is a multi-centred patient randomised superiority trial comparing an experimental strategy of once daily abdominal massage for 6 weeks against a control strategy of no massage in people with MS who have stated that their constipation is bothersome. The primary outcome is the Neurogenic Bowel Dysfunction Score at 24 weeks. Both groups will receive optimised advice plus the MS Society booklet on bowel management in MS, and will continue to receive usual care. Participants and their clinicians will not be blinded to the allocated intervention. Outcome measures are primarily self-reported and submitted anonymously. Central trial staff who will manage and analyse the trial data will be unaware of participant allocations. Analysis will follow intention-to-treat principles. This pragmatic randomised controlled trial will demonstrate if abdominal massage is an effective, cost-effective and viable addition to the treatment of NBD in people with MS. ClinicalTrials.gov, ISRCTN85007023 . Registered on 10 June 2014.

Endocrine and metabolic disorders associated with human immune deficiency virus infection.

PubMed

Unachukwu, C N; Uchenna, D I; Young, E E

2009-01-01

Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

The usefulness of MR defecography in the evaluation of pelvic floor dysfunction: our experience using 3T MRI.

PubMed

Al-Najar, Mahasen S; Ghanem, Ahmed F; AlRyalat, Saif Aldeen S; Al-Ryalat, Nosaiba T; Alhajahjeh, Sultan O

2017-09-01

To assess the usefulness of MR defecography in evaluating pelvic floor dysfunction, and to correlate several pelvic organ abnormalities with each other and with patients' symptoms and characteristics. MR defecographic examinations performed in 3T MRI machine of 95 patients (70 females, 25 males; mean age 48) were retrospectively reviewed. Pelvic organ abnormalities from all three compartments were recorded, including the anorectal junction descent, anterior rectocele, and cystocele. These were graded according to the known HMO system in relation to the pubococcygeal line. The correlation between these different abnormalities and their relation to patient symptoms and characteristics were evaluated. Anorectal junction descent and anterior rectocele were most commonly observed, predominantly manifesting in female patients. Both were associated with abnormalities from all compartments. The middle compartment was the least affected, and its abnormality of uterine/vaginal descent tended to occur in association with the anterior compartment abnormality (cystocele). Anismus was low in incidence, and was not associated with other compartments abnormalities. Both enterocele/peritoneocele and intussusception were uncommon. MR defecography is the modality of choice in assessing pelvic floor dysfunction, because it can neatly show various pelvic organ abnormalities from all compartments in a dynamic fashion, which are frequently coexistent. It can even show clinically silent or unsuspected abnormalities which can impact the management of patients.

Patterns of postictal cerebral perfusion in idiopathic generalized epilepsy: a multi-delay multi-parametric arterial spin labelling perfusion MRI study.

PubMed

Chen, Guangxiang; Lei, Du; Ren, Jiechuan; Zuo, Panli; Suo, Xueling; Wang, Danny J J; Wang, Meiyun; Zhou, Dong; Gong, Qiyong

2016-07-04

The cerebral haemodynamic status of idiopathic generalized epilepsy (IGE) is a very complicated process. Little attention has been paid to cerebral blood flow (CBF) alterations in IGE detected by arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI). However, the selection of an optimal delay time is difficult for single-delay ASL. Multi-delay multi-parametric ASL perfusion MRI overcomes the limitations of single-delay ASL. We applied multi-delay multi-parametric ASL perfusion MRI to investigate the patterns of postictal cerebral perfusion in IGE patients with absence seizures. A total of 21 IGE patients with absence seizures and 24 healthy control subjects were enrolled. IGE patients exhibited prolonged arterial transit time (ATT) in the left superior temporal gyrus. The mean CBF of IGE patients was significantly increased in the left middle temporal gyrus, left parahippocampal gyrus and left fusiform gyrus. Prolonged ATT in the left superior temporal gyrus was negatively correlated with the age at onset in IGE patients. This study demonstrated that cortical dysfunction in the temporal lobe and fusiform gyrus may be related to epileptic activity in IGE patients with absence seizures. This information can play an important role in elucidating the pathophysiological mechanism of IGE from a cerebral haemodynamic perspective.

Impact of perioperative liver dysfunction on in-hospital mortality and long-term survival in infective endocarditis patients.

PubMed

Diab, M; Sponholz, C; von Loeffelholz, C; Scheffel, P; Bauer, M; Kortgen, A; Lehmann, T; Färber, G; Pletz, M W; Doenst, T

2017-12-01

Infective endocarditis (IE) is often associated with multiorgan dysfunction and mortality. The impact of perioperative liver dysfunction (LD) on outcome remains unclear and little is known about factors leading to postoperative LD. We performed a retrospective, single-center analysis on 285 patients with left-sided IE without pre-existing chronic liver disease referred to our center between 2007 and 2013 for valve surgery. Sequential organ failure assessment (SOFA) score was used to evaluate organ dysfunction. Chi-square, Cox regression, and multivariate analyses were used for evaluation. Preoperative LD (Bilirubin >20 μmol/L) was present in 68 of 285 patients. New, postoperative LD occurred in 54 patients. Hypoxic hepatitis presented the most common origin of LD, accompanied with high short-term mortality. In-hospital mortality was higher in patients with preoperative and postoperative LD compared to patients without LD (51.5, 24.1, and 10.4%, respectively, p < 0.001). 5-year survival was worse in patients with pre- or postoperative LD compared to patients without LD (20.1, 37.1, and 57.0% respectively). A landmark analysis revealed similar 5-year survival between groups after patient discharge. Quality of life was similar between groups when patients survived the perioperative period. Logistic regression analysis identified duration of cardiopulmonary bypass and S. aureus infection as independent predictors of postoperative LD. Perioperative liver dysfunction in patients with infective endocarditis is an independent predictor of short- and long-term mortalities. After surviving the hospital stay, 5-year prognosis is not different and quality of life is not affected by LD. S. aureus and duration of cardiopulmonary bypass represent risk factors for postoperative LD.

New insights into the gut as the driver of critical illness and organ failure.

PubMed

Meng, Mei; Klingensmith, Nathan J; Coopersmith, Craig M

2017-04-01

The gut has long been hypothesized to be the 'motor' of multiple organ dysfunction syndrome. This review serves as an update on new data elucidating the role of the gut as the propagator of organ failure in critical illness. Under basal conditions, the gut absorbs nutrients and serves as a barrier that prevents approximately 40 trillion intraluminal microbes and their products from causing host injury. However, in critical illness, gut integrity is disrupted with hyperpermeability and increased epithelial apoptosis, allowing contamination of extraluminal sites that are ordinarily sterile. These alterations in gut integrity are further exacerbated in the setting of preexisting comorbidities. The normally commensal microflora is also altered in critical illness, with increases in microbial virulence and decreases in diversity, which leads to further pathologic responses within the host. All components of the gut are adversely impacted by critical illness. Gut injury can not only propagate local damage, but can also cause distant injury and organ failure. Understanding how the multifaceted components of the gut interact and how these are perturbed in critical illness may play an important role in turning off the 'motor' of multiple organ dysfunction syndrome in the future.

THE EPITHELIUM AS A TARGET IN SEPSIS.

PubMed

Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gómez, Alonso; Murray, Patrick; Gómez, Hernando; Kellum, John A

2016-03-01

Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future.

Female Sexual Dysfunction Among Muslim Women: Increasing Awareness to Improve Overall Evaluation and Treatment.

PubMed

Rahman, Sameena

2018-04-17

Muslim women are an increasingly underserved population in the United States and worldwide. Diagnosis and treatment of female sexual dysfunction bring unique challenges because of the conservative nature of those practicing the religion. Several cultural and religious codes of conduct affect sexual behavior and the dysfunction that can ensue. To assess and describe the types of sexual dysfunction that have been found in Muslim women internationally and encourage a better understanding of their issues to enhance health care delivery. A comprehensive review of the literature through Ovid and PubMed was performed in search of articles reviewing female sexual dysfunction, Muslim women, and Islam. A brief explanation and review of the interpretations of sexuality within Islam are discussed. The link is made between conservative sexual relations and interpretations and the types of sexual dysfunction experienced. Female sexual dysfunction is explored in relation to how female chastity is extolled and how cultural procedures continue despite the ethical and health concerns related to them. Most Muslim women experience sexual dysfunction similar to other women, including arousal, desire, and orgasmic disorders related to organic and psychologic factors. Sexual pain disorders might be more prevalent in this population, particularly concerning unconsummated marriage. There are special concerns related to maintaining virginity and preserving the hymen until marriage. Female genital cutting, practiced by some Muslim countries, has potential sexual consequences. Understanding Islamic views on sexuality and how they can affect sexual dysfunction in Muslim women is critical in opening lines of communication with patients and approaching female sexual dysfunction impartially. Although some issues that arise might introduce ethical dilemmas for the provider, having the cultural competence to address these issues will facilitate improved health care delivery. Rahman S. Female Sexual Dysfunction Among Muslim Women: Increasing Awareness to Improve Overall Evaluation and Treatment. Sex Med Rev 2018;X:XX-XX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Dysfunctional uterine bleeding in ovulatory women.

PubMed

Strickler, R C

1985-01-01

Ovulatory dysfunctional uterine bleeding (DUB), a disease prevalent in the latter half of the reproductive years, is diagnosed when organic causes for bleeding have been excluded by clinical, laboratory, and surgical diagnostic means. Disordered prostaglandin metabolism within the endometrium explains most cases of DUB. Nonsteroidal antiinflammatory drugs, oral contraceptives, and oral progestin are effective medical alternatives for women who wish to retain their uterus or to avoid surgery. Hysterectomy is a rapid cure for DUB and is a therapy that is acceptable to many, if not most, women.

Love and sex after 60: how to evaluate and treat the impotent older man. A roundtable discussion: Part 2.

PubMed

Butler, R N; Lewis, M I; Hoffman, E; Whitehead, E D

1994-10-01

In the medical evaluation of older men with erectile dysfunction, obtain a detailed history to determine whether the dysfunction is organic or psychogenic. Determine if there are underlying pathologic processes--most notably vascular diseases--or other factors responsible for the dysfunction, such as medications or nerve or arterial damage from surgery. Lifestyle changes in mid-life (regular exercise, a low-fat diet, and smoking cessation) increase a man's chances of remaining potent as he grows older. Treatments for impotence include injection therapy, vacuum devices, and implants. Each therapy has advantages and disadvantages, and the informed patient plays an important role in choosing the therapy that is right for him.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THYROID DYSFUNCTION CASE FINDING.

PubMed

Hennessey, James V; Garber, Jeffrey R; Woeber, Kenneth A; Cobin, Rhoda; Klein, Irwin

2016-02-01

Hypothyroidism and hyperthyroidism can be readily diagnosed and can be treated in a safe, cost-effective manner. Professional organizations have given guidance on how and when to employ thyroid-stimulating hormone testing for the detection of thyroid dysfunction. Most recently, the United States Preventive Services Task Force did not endorse screening for thyroid dysfunction based on a lack of proven benefit and potential harm of treating those with thyroid dysfunction, which is mostly subclinical disease. The American Association of Clinical Endocrinologists (AACE) is concerned that this may discourage physicians from testing for thyroid dysfunction when clinically appropriate. Given the lack of specificity of thyroid-associated symptoms, the appropriate diagnosis of thyroid disease requires biochemical confirmation. The Thyroid Scientific Committee of the AACE has produced this White Paper to highlight the important difference between screening and case-based testing in the practice of clinical medicine. We recommend that thyroid dysfunction should be frequently considered as a potential etiology for many of the nonspecific complaints that physicians face daily. The application and success of safe and effective interventions are dependent on an accurate diagnosis. We, therefore, advocate for an aggressive case-finding approach, based on identifying those persons most likely to have thyroid disease that will benefit from its treatment.

Familial knockin mutation of LRRK2 causes lysosomal dysfunction and accumulation of endogenous insoluble α-synuclein in neurons.

PubMed

Schapansky, Jason; Khasnavis, Saurabh; DeAndrade, Mark P; Nardozzi, Jonathan D; Falkson, Samuel R; Boyd, Justin D; Sanderson, John B; Bartels, Tim; Melrose, Heather L; LaVoie, Matthew J

2018-03-01

Missense mutations in the multi-domain kinase LRRK2 cause late onset familial Parkinson's disease. They most commonly with classic proteinopathy in the form of Lewy bodies and Lewy neurites comprised of insoluble α-synuclein, but in rare cases can also manifest tauopathy. The normal function of LRRK2 has remained elusive, as have the cellular consequences of its mutation. Data from LRRK2 null model organisms and LRRK2-inhibitor treated animals support a physiological role for LRRK2 in regulating lysosome function. Since idiopathic and LRRK2-linked PD are associated with the intraneuronal accumulation of protein aggregates, a series of critical questions emerge. First, how do pathogenic mutations that increase LRRK2 kinase activity affect lysosome biology in neurons? Second, are mutation-induced changes in lysosome function sufficient to alter the metabolism of α-synuclein? Lastly, are changes caused by pathogenic mutation sensitive to reversal with LRRK2 kinase inhibitors? Here, we report that mutation of LRRK2 induces modest but significant changes in lysosomal morphology and acidification, and decreased basal autophagic flux when compared to WT neurons. These changes were associated with an accumulation of detergent-insoluble α-synuclein and increased neuronal release of α-synuclein and were reversed by pharmacologic inhibition of LRRK2 kinase activity. These data demonstrate a critical and disease-relevant influence of native neuronal LRRK2 kinase activity on lysosome function and α-synuclein homeostasis. Furthermore, they also suggest that lysosome dysfunction, altered neuronal α-synuclein metabolism, and the insidious accumulation of aggregated protein over decades may contribute to pathogenesis in this late-onset form of familial PD. Copyright © 2017 Elsevier Inc. All rights reserved.

Fractal Dimension of EEG Activity Senses Neuronal Impairment in Acute Stroke

PubMed Central

Zappasodi, Filippo; Olejarczyk, Elzbieta; Marzetti, Laura; Assenza, Giovanni; Pizzella, Vittorio; Tecchio, Franca

2014-01-01

The brain is a self-organizing system which displays self-similarities at different spatial and temporal scales. Thus, the complexity of its dynamics, associated to efficient processing and functional advantages, is expected to be captured by a measure of its scale-free (fractal) properties. Under the hypothesis that the fractal dimension (FD) of the electroencephalographic signal (EEG) is optimally sensitive to the neuronal dysfunction secondary to a brain lesion, we tested the FD’s ability in assessing two key processes in acute stroke: the clinical impairment and the recovery prognosis. Resting EEG was collected in 36 patients 4–10 days after a unilateral ischemic stroke in the middle cerebral artery territory and 19 healthy controls. National Health Institute Stroke Scale (NIHss) was collected at T0 and 6 months later. Highuchi FD, its inter-hemispheric asymmetry (FDasy) and spectral band powers were calculated for EEG signals. FD was smaller in patients than in controls (1.447±0.092 vs 1.525±0.105) and its reduction was paired to a worse acute clinical status. FD decrease was associated to alpha increase and beta decrease of oscillatory activity power. Larger FDasy in acute phase was paired to a worse clinical recovery at six months. FD in our patients captured the loss of complexity reflecting the global system dysfunction resulting from the structural damage. This decrease seems to reveal the intimate nature of structure-function unity, where the regional neural multi-scale self-similar activity is impaired by the anatomical lesion. This picture is coherent with neuronal activity complexity decrease paired to a reduced repertoire of functional abilities. FDasy result highlights the functional relevance of the balance between homologous brain structures’ activities in stroke recovery. PMID:24967904

Fractal dimension of EEG activity senses neuronal impairment in acute stroke.

PubMed

Zappasodi, Filippo; Olejarczyk, Elzbieta; Marzetti, Laura; Assenza, Giovanni; Pizzella, Vittorio; Tecchio, Franca

2014-01-01

The brain is a self-organizing system which displays self-similarities at different spatial and temporal scales. Thus, the complexity of its dynamics, associated to efficient processing and functional advantages, is expected to be captured by a measure of its scale-free (fractal) properties. Under the hypothesis that the fractal dimension (FD) of the electroencephalographic signal (EEG) is optimally sensitive to the neuronal dysfunction secondary to a brain lesion, we tested the FD's ability in assessing two key processes in acute stroke: the clinical impairment and the recovery prognosis. Resting EEG was collected in 36 patients 4-10 days after a unilateral ischemic stroke in the middle cerebral artery territory and 19 healthy controls. National Health Institute Stroke Scale (NIHss) was collected at T0 and 6 months later. Highuchi FD, its inter-hemispheric asymmetry (FDasy) and spectral band powers were calculated for EEG signals. FD was smaller in patients than in controls (1.447±0.092 vs 1.525±0.105) and its reduction was paired to a worse acute clinical status. FD decrease was associated to alpha increase and beta decrease of oscillatory activity power. Larger FDasy in acute phase was paired to a worse clinical recovery at six months. FD in our patients captured the loss of complexity reflecting the global system dysfunction resulting from the structural damage. This decrease seems to reveal the intimate nature of structure-function unity, where the regional neural multi-scale self-similar activity is impaired by the anatomical lesion. This picture is coherent with neuronal activity complexity decrease paired to a reduced repertoire of functional abilities. FDasy result highlights the functional relevance of the balance between homologous brain structures' activities in stroke recovery.

Using multi-disciplinary strategic master facilities planning for organizations experiencing programmatic re-direction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heubach, J.G.; Weimer, W.C.; Bruce, W.A.

Facility master planning is critical to the future productivity of a laboratory and the quality of worklife for the laboratory staff. For organizations undergoing programmatic re-direction, a master facility planning approach linked to the organization`s strategic planning process is even more important. Major changes in an organization such as programmatic re-direction can significantly impact a broad range of variables which exceed the expertise of traditional planning teams, e.g., capacity variability, work team organization, organizational culture, and work process simplification. By expanding the diversity of the participants of the planning team, there is a greater likelihood that a research organization`s scientific,more » organizational, economic, and employees` needs can be meshed in the strategic plan and facility plan. Recent recommendations from facility planners suggest drawing from diverse fields in building multi-disciplinary planning teams: Architecture, engineering, natural science, social psychology, and strategic planning (Gibson,1993). For organizations undergoing significant operational or culture change, the master facility planning team should also include members with expertise in organizational effectiveness, industrial engineering, human resources, and environmental psychology. A recent planning and design project provides an example which illustrates the use of an expanded multi-disciplinary team engaged in planning laboratory renovations for a research organization undergoing programmatic re-direction. The purpose of the proposed poster session is to present a multi-disciplinary master facility planning process linked to an organization`s strategic planning process or organizational strategies.« less

A peripheral blood transcriptome biomarker test to diagnose functional recovery potential in advanced heart failure.

PubMed

Deng, Mario C

2018-05-08

Heart failure (HF) is a complex clinical syndrome that causes systemic hypoperfusion and failure to meet the body's metabolic demands. In an attempt to compensate, chronic upregulation of the sympathetic nervous system and renin-angiotensin-aldosterone leads to further myocardial injury, HF progression and reduced O 2 delivery. This triggers progressive organ dysfunction, immune system activation and profound metabolic derangements, creating a milieu similar to other chronic systemic diseases and presenting as advanced HF with severely limited prognosis. We hypothesize that 1-year survival in advanced HF is linked to functional recovery potential (FRP), a novel clinical composite parameter that includes HF severity, secondary organ dysfunction, co-morbidities, frailty, disabilities as well as chronological age and that can be diagnosed by a molecular biomarker.

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study

PubMed Central

2010-01-01

Introduction Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. Methods We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. Results We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days. Conclusions In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables. PMID:20429897

SISL (ScreeningsInstrument Schisis Leuven): assessment of cleft palate speech, resonance and myofunction.

PubMed

Breuls, M; Sell, D; Manders, E; Boulet, E; Vander Poorten, V

2006-01-01

This paper presents an assessment protocol for the evaluation and description of speech, resonance and myofunctional characteristics commonly associated with cleft palate and/or velopharyngeal dysfunction. The protocol is partly based on the GOS.SP.ASS'98 and adapted to Flemish. It focuses on the relevant aspects of cleft type speech necessary to facilitate assessment, adequate diagnosis and management planning in a multi-disciplinary setting of cleft team care.

Erectile Dysfunction: Viagra and Other Oral Medications

MedlinePlus

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Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System.

PubMed

Rachdaoui, Nadia; Sarkar, Dipak K

2017-01-01

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.

Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children.

PubMed

Matics, Travis J; Sanchez-Pinto, L Nelson

2017-10-02

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) score to grade organ dysfunction in adult patients with suspected infection. However, the SOFA score is not adjusted for age and therefore not suitable for children. To adapt and validate a pediatric version of the SOFA score (pSOFA) in critically ill children and to evaluate the Sepsis-3 definitions in patients with confirmed or suspected infection. This retrospective observational cohort study included all critically ill children 21 years or younger admitted to a 20-bed, multidisciplinary, tertiary pediatric intensive care unit between January 1, 2009 and August 1, 2016. Data on these children were obtained from an electronic health record database. The pSOFA score was developed by adapting the original SOFA score with age-adjusted cutoffs for the cardiovascular and renal systems and by expanding the respiratory criteria to include noninvasive surrogates of lung injury. Daily pSOFA scores were calculated from admission until day 28 of hospitalization, discharge, or death (whichever came first). Three additional pediatric organ dysfunction scores were calculated for comparison. Organ dysfunction measured by the pSOFA score, and sepsis and septic shock according to the Sepsis-3 definitions. The primary outcome was in-hospital mortality. The daily pSOFA scores and additional pediatric organ dysfunction scores were compared. Performance was evaluated using the area under the curve. The pSOFA score was then used to assess the Sepsis-3 definitions in the subgroup of children with confirmed or suspected infection. In all, 6303 patients with 8711 encounters met inclusion criteria. Each encounter was treated independently. Of the 8482 survivors of hospital encounters, 4644 (54.7%) were male and the median (interquartile range [IQR]) age was 69 (17-156) months. Among the 229 nonsurvivors, 127 (55.4%) were male with a median (IQR) age of 43 (8-144) months. In-hospital mortality was 2.6%. The maximum pSOFA score had excellent discrimination for in-hospital mortality, with an area under the curve of 0.94 (95% CI, 0.92-0.95). The pSOFA score had a similar or better performance than other pediatric organ dysfunction scores. According to the Sepsis-3 definitions, 1231 patients (14.1%) were classified as having sepsis and had a mortality rate of 12.1%, and 347 (4.0%) had septic shock and a mortality rate of 32.3%. Patients with sepsis were more likely to die than patients with confirmed or suspected infection but no sepsis (odds ratio, 18; 95% CI, 11-28). Of the 229 patients who died during their hospitalization, 149 (65.0%) had sepsis or septic shock during their course. The pSOFA score was adapted and validated with age-adjusted variables in critically ill children. Using the pSOFA score, the Sepsis-3 definitions were assessed in children with confirmed or suspected infection. This study is the first assessment, to date, of the Sepsis-3 definitions in critically ill children. Use of these definitions in children is feasible and shows promising results.

From data to knowledge: The future of multi-omics data analysis for the rhizosphere

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen White, Richard; Borkum, Mark I.; Rivas-Ubach, Albert

The rhizosphere is the interface between a plant's roots and its surrounding soil. The rhizosphere microbiome, a complex microbial ecosystem, nourishes the terrestrial biosphere. Integrated multi-omics is a modern approach to systems biology that analyzes and interprets the datasets of multiple -omes of both individual organisms and multi-organism communities and consortia. The successful usage and application of integrated multi-omics to rhizospheric science is predicated upon the availability of rhizosphere-specific data, metadata and software. This review analyzes the availability of multi-omics data, metadata and software for rhizospheric science, identifying potential issues, challenges and opportunities.

Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

PubMed

Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D; Tattersall, Matthew C; Volpe, Gustavo J; Ambale-Venkatesh, Bharath; Nasir, Khurram; Wu, Colin O; Polak, Joseph F; Korcarz, Claudia E; Stein, James H; Carr, James; Watson, Karol E; Bluemke, David A; Lima, João A C

2015-04-01

The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min. In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The subchronic phencyclidine rat model: relevance for the assessment of novel therapeutics for cognitive impairment associated with schizophrenia.

PubMed

Janhunen, Sanna K; Svärd, Heta; Talpos, John; Kumar, Gaurav; Steckler, Thomas; Plath, Niels; Lerdrup, Linda; Ruby, Trine; Haman, Marie; Wyler, Roger; Ballard, Theresa M

2015-11-01

Current treatments for schizophrenia have modest, if any, efficacy on cognitive dysfunction, creating a need for novel therapies. Their development requires predictive animal models. The N-methyl-D-aspartate (NMDA) hypothesis of schizophrenia indicates the use of NMDA antagonists, like subchronic phencyclidine (scPCP) to model cognitive dysfunction in adult animals. The objective of this study was to assess the scPCP model by (1) reviewing published findings of scPCP-induced neurochemical changes and effects on cognitive tasks in adult rats and (2) comparing findings from a multi-site study to determine scPCP effects on standard and touchscreen cognitive tasks. Across four research sites, the effects of scPCP (typically 5 mg/kg twice daily for 7 days, followed by at least 7-day washout) in adult male Lister Hooded rats were studied on novel object recognition (NOR) with 1-h delay, acquisition and reversal learning in Morris water maze and touchscreen-based visual discrimination. Literature findings showed that scPCP impaired attentional set-shifting (ASST) and NOR in several labs and induced a variety of neurochemical changes across different labs. In the multi-site study, scPCP impaired NOR, but not acquisition or reversal learning in touchscreen or water maze. Yet, this treatment regimen induced locomotor hypersensitivity to acute PCP until 13-week post-cessation. The multi-site study confirmed that scPCP impaired NOR and ASST only and demonstrated the reproducibility and usefulness of the touchscreen approach. Our recommendation, prior to testing novel therapeutics in the scPCP model, is to be aware that further work is required to understand the neurochemical changes and specificity of the cognitive deficits.

Urogenital consequences in ageing women.

PubMed

Doumouchtsis, Stergios K; Chrysanthopoulou, Eleftheria L

2013-10-01

Various anatomical, physiological, genetic, lifestyle and reproductive factors interact throughout a woman's life span and contribute to pelvic floor disorders. Ageing affects pelvic floor anatomy and function, which can result in a variety of disorders, such as pelvic organ prolapse, lower urinary tract symptoms, dysfunctional bowel and bladder evacuation, and sexual dysfunction. The exact mechanisms and pathophysiological processes by which ageing affects pelvic floor and lower urinary and gastrointestinal tract anatomy and function are not always clear. In most cases, it is difficult to ascertain the exact role of ageing per se as an aetiological, predisposing or contributing factor. Other conditions associated with ageing that may co-exist, such as changes in mental status, can result in different types of pelvic floor dysfunction (e.g. functional incontinence). Pelvic organ dysfunction may be associated with significant morbidity and affect quality of life. These groups of patients often pose difficult diagnostic and therapeutic dilemmas owing to complex medical conditions and concurrent morbidities. In this chapter, we summarise the current evidence on the management of pelvic floor disorders, with emphasis on elderly women and the associations between the ageing process and these disorders. Clinicians with an understanding of the affect of ageing on the pelvic floor and lower urinary and gastrointestinal tract anatomy and function, and the complex interplay of other comorbidities, will be able to investigate, diagnose and treat appropriately there women. A holistic approach may result in substantial improvements in their quality of life. Copyright © 2013. Published by Elsevier Ltd.

Control, Control, Complete Control!!! Neurotic Control Relationships and the Development of Dysfunctional Organizational Structures.

ERIC Educational Resources Information Center

Kersten, Astrid

A case study illustrates the concept of the neurotic organization by describing the development of "Central Control College" over a period of 11 years. In this period of time, the college moved from a small, informal organization to a highly developed compulsive institution. The image of neurosis has been applied in the organizational…

Our Dancing Daughters: "The Queen, Little Miss Sunshine," and Dysfunctional Families

ERIC Educational Resources Information Center

Beck, Bernard

2007-01-01

Local cultures survive when they are successfully passed to new generations in spite of the many oppressions and seductions delivered by surrounding cultures--dominant, variant, and deviant. The groups that use those small cultural systems must be organized in a way that assures that passage, and organization of any important social activity means…

Immune dysfunction in cirrhosis.

PubMed

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-03-14

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality.

Immune dysfunction in cirrhosis

PubMed Central

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-01-01

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

An international Urogynecological association (IUGA)/international continence society (ICS) joint report on the terminology for the assessment of sexual health of women with pelvic floor dysfunction.

PubMed

Rogers, Rebecca G; Pauls, Rachel N; Thakar, Ranee; Morin, Melanie; Kuhn, Annette; Petri, Eckhard; Fatton, Brigitte; Whitmore, Kristene; Kingsberg, Sheryl A; Lee, Joseph

2018-05-01

The terminology in current use for sexual function and dysfunction in women with pelvic floor disorders lacks uniformity, which leads to uncertainty, confusion, and unintended ambiguity. The terminology for the sexual health of women with pelvic floor dysfunction needs to be collated in a clinically-based consensus report. This report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA), and the International Continence Society (ICS), assisted at intervals by many external referees. Internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Importantly, this report is not meant to replace, but rather complement current terminology used in other fields for female sexual health and to clarify terms specific to women with pelvic floor dysfunction. A clinically based terminology report for sexual health in women with pelvic floor dysfunction encompassing over 100 separate definitions, has been developed. Key aims have been to make the terminology interpretable by practitioners, trainees, and researchers in female pelvic floor dysfunction. Interval review (5-10 years) is anticipated to keep the document updated and as widely acceptable as possible. A consensus-based terminology report for female sexual health in women with pelvic floor dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for the assessment of sexual health of women with pelvic floor dysfunction.

PubMed

Rogers, Rebecca G; Pauls, Rachel N; Thakar, Ranee; Morin, Melanie; Kuhn, Annette; Petri, Eckhard; Fatton, Brigitte; Whitmore, Kristene; Kinsberg, Sheryl; Lee, Joseph

2018-04-01

The terminology in current use for sexual function and dysfunction in women with pelvic floor disorders lacks uniformity, which leads to uncertainty, confusion, and unintended ambiguity. The terminology for the sexual health of women with pelvic floor dysfunction needs to be collated in a clinically-based consensus report. This report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA), and the International Continence Society (ICS), assisted at intervals by many external referees. Internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Importantly, this report is not meant to replace, but rather complement current terminology used in other fields for female sexual health and to clarify terms specific to women with pelvic floor dysfunction. A clinically based terminology report for sexual health in women with pelvic floor dysfunction encompassing over 100 separate definitions, has been developed. Key aims have been to make the terminology interpretable by practitioners, trainees, and researchers in female pelvic floor dysfunction. Interval review (5-10 years) is anticipated to keep the document updated and as widely acceptable as possible. A consensus-based terminology report for female sexual health in women with pelvic floor dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research. © 2018 Wiley Periodicals, Inc.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

PubMed

Szakmany, T; Pugh, R; Kopczynska, M; Lundin, R M; Sharif, B; Morgan, P; Ellis, G; Abreu, J; Kulikouskaya, S; Bashir, K; Galloway, L; Al-Hassan, H; Grother, T; McNulty, P; Seal, S T; Cains, A; Vreugdenhil, M; Abdimalik, M; Dennehey, N; Evans, G; Whitaker, J; Beasant, E; Hall, C; Lazarou, M; Vanderpump, C V; Harding, K; Duffy, L; Guerrier Sadler, A; Keeling, R; Banks, C; Ng, S W Y; Heng, S Y; Thomas, D; Puw, E W; Otahal, I; Battle, C; Minik, O; Lyons, R A; Hall, J E

2018-02-01

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Australian perioperative nurses' experiences of assisting in multi-organ procurement surgery: a grounded theory study.

PubMed

Smith, Zaneta; Leslie, Gavin; Wynaden, Dianne

2015-03-01

Multi-organ procurement surgical procedures through the generosity of deceased organ donors, have made an enormous impact on extending the lives of recipients. There is a dearth of in-depth knowledge relating to the experiences of perioperative nurses working closely with organ donors undergoing multi-organ procurement surgical procedures. The aim of this study was to address this gap by describing the perioperative nurses experiences of participating in multi-organ procurement surgical procedures and interpreting these findings as a substantive theory. This qualitative study used grounded theory methodology to generate a substantive theory of the experiences of perioperative nurses participating in multi-organ procurement surgery. Recruitment of participants took place after the study was advertised via a professional newsletter and journal. The study was conducted with participants from metropolitan, rural and regional areas of two Australian states; New South Wales and Western Australia. Thirty five perioperative nurse participants with three to 39 years of professional nursing experience informed the study. Semi structured in-depth interviews were undertaken from July 2009 to April 2010 with a mean interview time of 60 min. Interview data was transcribed verbatim and analysed using the constant comparative method. The study results draw attention to the complexities that exist for perioperative nurses when participating in multi-organ procurement surgical procedures reporting a basic social psychological problem articulated as hiding behind a mask and how they resolved this problem by the basic social psychological process of finding meaning. This study provides a greater understanding of how these surgical procedures impact on perioperative nurses by providing a substantive theory of this experience. The findings have the potential to guide further research into this challenging area of nursing practice with implications for clinical initiatives, management practices and education. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

PubMed

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

Changing character: A narrative review of personality change in psychotherapies for personality disorder.

PubMed

Keefe, John R; DeRubeis, Robert J

2018-01-19

Personality disorder (PD) is a negative prognostic indicator for treatment, and absolute improvements in functioning among these patients are often modest. This may be because personality features that give rise to dysfunction in PD are not targeted optimally during most treatments. Attachment, mentalization, core beliefs, and personality organization/defense use were identified as personality constructs that have been pursued in treatment studies and that are proposed to underlie PD. All constructs correlate with psychiatric symptoms, PD diagnosis, and functioning. Defense mechanisms and core beliefs further distinguish specific PDs, whereas personality organization separates more versus less severe PDs. Evidence from treatment and naturalistic studies indicate that maturation of defense mechanisms temporally precedes improvements in symptoms and functioning. Changes in attachment and mentalization correlate with some outcomes, but mediation of improvement has not been established. In psychodynamic therapy, transference interpretations may promote amelioration of personality dysfunction. With the exception of attachment, the experimental literature is lacking that could explicate the mechanisms by which these personality constructs maintain psychosocial dysfunction. Future research should aim to identify changes in these mechanisms that mediate positive outcomes in PD, as well as the specific therapeutic procedures that best promote positive change in PD.

Psychological impact and sexual dysfunction in men with and without spinal cord injury.

PubMed

Cobo Cuenca, Ana I; Sampietro-Crespo, Antonio; Virseda-Chamorro, Miguel; Martín-Espinosa, Noelia

2015-02-01

The World Health Organization recognizes sexual health as a fundamental right that should be guaranteed to all individuals. Sexual dysfunction affects various aspects in the lives (physical, psychic, and social) of affected persons. To assess the different types of sexual dysfunction, the quality of life (QOL), depression, anxiety, and levels of self-esteem observed in 165 men with sexual dysfunction, both with and without spinal cord injury (SCI). Case control study of 85 men with SCI and sexual dysfunction, and 80 men without SCI that have sexual dysfunction. The Sexual Health Evaluation Scale, the Fugl-Meyer Life Satisfaction Questionnaire scale, the Hospital Anxiety and Depression Scale, the Evaluation of the Sexual Health Scale, and Rosenberg's Self-esteem Scale were all used for data collection. Of the members in group A (with SCI), 89.4% (76) showed erectile dysfunction, and 75.2% (64) reported anejaculation. In group B (without SCI), 75 (96.8%) showed erectile dysfunction, and 58.7% (47) had disorders of sexual desire. In group A, 16.47 % (14) showed signs of depression, and 35.3% (30) had signs of anxiety. In group B, 30% (24) had elevated scores regarding depression, and 48.75% (39) had high scores for anxiety. All of the participants reported a high general QOL and a high satisfaction with their QOL but reported that their satisfaction with their sexual lives was only at the acceptable level. Social QOL is significantly higher in the SCI group (t Student P=0.031). The QOL, self-esteem, and anxiety and depression levels are significantly correlated. Men with sexual dysfunction strive to adapt to their situations, with the relationship between the type of sexual dysfunction and the QOL, mood (depression), and self-esteem all being important considerations. Sexuality and employment status are the areas where men with spinal cord injuries report less satisfaction. © 2014 International Society for Sexual Medicine.

Positive therapeutic response to lithium in hypomania secondary to organic brain syndrome.

PubMed

Rosenbaum, A H; Barry, M J

1975-10-01

A 57-year-old man with no personal or family history of manic-depressive disease developed symptoms of hypomania after a cerebrovascular accident and surgical trauma to the brain. The patient responded well to lithium carbonate treatment over a 2-year period. Although this therapy is contraindicated in cases of organic brain syndrome, the authors suggest that it should be considered in the management of hypomanic behavior following organic brain dysfunction.

Nitrate tolerance, oxidative stress, and mitochondrial function: another worrisome chapter on the effects of organic nitrates

PubMed Central

Parker, John D.

2004-01-01

A shortcoming in the clinical use of organic nitrates is the development of tolerance. Recent data have suggested that the denitrification of organic nitrates is mediated by mitochondrial aldehyde dehydrogenase and that dysfunction of this enzyme is an important cause of tolerance. In this issue of the JCI, evidence in support of this hypothesis is presented in an in vivo model of nitrate tolerance. PMID:14755331

A New Multi-Sensor Track Fusion Architecture for Multi-Sensor Information Integration

DTIC Science & Technology

2004-09-01

NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION ...NAME(S) AND ADDRESS(ES) Lockheed Martin Aeronautical Systems Company,Marietta,GA,3063 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...tracking process and degrades the track accuracy. ARCHITECHTURE OF MULTI-SENSOR TRACK FUSION MODEL The Alpha

Surface Modified Particles By Multi-Step Addition And Process For The Preparation Thereof

DOEpatents

Cook, Ronald Lee; Elliott, Brian John; Luebben, Silvia DeVito; Myers, Andrew William; Smith, Bryan Matthew

2006-01-17

The present invention relates to a new class of surface modified particles and to a multi-step surface modification process for the preparation of the same. The multi-step surface functionalization process involves two or more reactions to produce particles that are compatible with various host systems and/or to provide the particles with particular chemical reactivities. The initial step comprises the attachment of a small organic compound to the surface of the inorganic particle. The subsequent steps attach additional compounds to the previously attached organic compounds through organic linking groups.

Mathematical multi-scale model of the cardiovascular system including mitral valve dynamics. Application to ischemic mitral insufficiency

PubMed Central

2011-01-01

Background Valve dysfunction is a common cardiovascular pathology. Despite significant clinical research, there is little formal study of how valve dysfunction affects overall circulatory dynamics. Validated models would offer the ability to better understand these dynamics and thus optimize diagnosis, as well as surgical and other interventions. Methods A cardiovascular and circulatory system (CVS) model has already been validated in silico, and in several animal model studies. It accounts for valve dynamics using Heaviside functions to simulate a physiologically accurate "open on pressure, close on flow" law. However, it does not consider real-time valve opening dynamics and therefore does not fully capture valve dysfunction, particularly where the dysfunction involves partial closure. This research describes an updated version of this previous closed-loop CVS model that includes the progressive opening of the mitral valve, and is defined over the full cardiac cycle. Results Simulations of the cardiovascular system with healthy mitral valve are performed, and, the global hemodynamic behaviour is studied compared with previously validated results. The error between resulting pressure-volume (PV) loops of already validated CVS model and the new CVS model that includes the progressive opening of the mitral valve is assessed and remains within typical measurement error and variability. Simulations of ischemic mitral insufficiency are also performed. Pressure-Volume loops, transmitral flow evolution and mitral valve aperture area evolution follow reported measurements in shape, amplitude and trends. Conclusions The resulting cardiovascular system model including mitral valve dynamics provides a foundation for clinical validation and the study of valvular dysfunction in vivo. The overall models and results could readily be generalised to other cardiac valves. PMID:21942971

Pathophysiology of Cardiopulmonary Bypass: Current Strategies for the Prevention and Treatment of Anemia, Coagulopathy, and Organ Dysfunction.

PubMed

Esper, Stephen A; Subramaniam, Kathirvel; Tanaka, Kenichi A

2014-06-01

The techniques and equipment of cardiopulmonary bypass (CPB) have evolved over the past 60 years, and numerous numbers of cardiac surgical procedures are conducted around the world using CPB. Despite more widespread applications of percutaneous coronary and valvular interventions, the need for cardiac surgery using CPB remains the standard approach for certain cardiac pathologies because some patients are ineligible for percutaneous procedures, or such procedures are unsuccessful in some. The ageing patient population for cardiac surgery poses a number of clinical challenges, including anemia, decreased cardiopulmonary reserve, chronic antithrombotic therapy, neurocognitive dysfunction, and renal insufficiency. The use of CPB is associated with inductions of systemic inflammatory responses involving both cellular and humoral interactions. Inflammatory pathways are complex and redundant, and thus, the reactions can be profoundly amplified to produce a multiorgan dysfunction that can manifest as capillary leak syndrome, coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive decline. In this review, pathophysiological aspects of CPB are considered from a practical point of view, and preventive strategies for hemodilutional anemia, coagulopathy, inflammation, metabolic derangement, and neurocognitive and renal dysfunction are discussed. © The Author(s) 2014.

Age-related changes in endothelial function and blood flow regulation.

PubMed

Toda, Noboru

2012-02-01

Vascular endothelial dysfunction is regarded as a primary phenotypic expression of normal human aging. This senescence-induced disorder is the likely culprit underlying the increased cardiovascular and metabolic disease risks associated with aging. The rate of this age-dependent deterioration is largely influenced by the poor-quality lifestyle choice, such as smoking, sedentary daily life, chronic alcohol ingestion, high salt intake, unbalanced diet, and mental stress; and it is accelerated by cardiovascular and metabolic diseases. Although minimizing these detrimental factors is the best course of action, nonetheless chronological age steadily impairs endothelial function through reduced endothelial nitric oxide synthase (eNOS) expression/action, accelerated nitric oxide (NO) degradation, increased phosphodiesterase activity, inhibition of NOS activity by endogenous NOS inhibitors, increased production of reactive oxygen species, inflammatory reactions, decreased endothelial progenitor cell number and function, and impaired telomerase activity or telomere shortening. Endothelial dysfunction in regional vasculatures results in cerebral hypoperfusion triggering cognitive dysfunction and Alzheimer's disease, coronary artery insufficiency, penile erectile dysfunction, and circulatory failures in other organs and tissues. Possible prophylactic measures to minimize age-related endothelial dysfunction are also summarized in this review. Copyright © 2011 Elsevier Inc. All rights reserved.

μOrgano: A Lego®-Like Plug & Play System for Modular Multi-Organ-Chips.

PubMed

Loskill, Peter; Marcus, Sivan G; Mathur, Anurag; Reese, Willie Mae; Healy, Kevin E

2015-01-01

Human organ-on-a-chip systems for drug screening have evolved as feasible alternatives to animal models, which are unreliable, expensive, and at times erroneous. While chips featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of the organ-on-a-chip technology is revealed by connecting multiple organs on one chip to create a single integrated system for sophisticated fundamental biological studies and devising therapies for disease. Furthermore, since most organ-on-a-chip systems require special protocols with organ-specific media for the differentiation and maturation of the tissues, multi-organ systems will need to be temporally customizable and flexible in terms of the time point of connection of the individual organ units. We present a customizable Lego®-like plug & play system, μOrgano, which enables initial individual culture of single organ-on-a-chip systems and subsequent connection to create integrated multi-organ microphysiological systems. As a proof of concept, the μOrgano system was used to connect multiple heart chips in series with excellent cell viability and spontaneously physiological beat rates.

μOrgano: A Lego®-Like Plug & Play System for Modular Multi-Organ-Chips

PubMed Central

Loskill, Peter; Marcus, Sivan G.; Mathur, Anurag; Reese, Willie Mae; Healy, Kevin E.

2015-01-01

Human organ-on-a-chip systems for drug screening have evolved as feasible alternatives to animal models, which are unreliable, expensive, and at times erroneous. While chips featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of the organ-on-a-chip technology is revealed by connecting multiple organs on one chip to create a single integrated system for sophisticated fundamental biological studies and devising therapies for disease. Furthermore, since most organ-on-a-chip systems require special protocols with organ-specific media for the differentiation and maturation of the tissues, multi-organ systems will need to be temporally customizable and flexible in terms of the time point of connection of the individual organ units. We present a customizable Lego®-like plug & play system, μOrgano, which enables initial individual culture of single organ-on-a-chip systems and subsequent connection to create integrated multi-organ microphysiological systems. As a proof of concept, the μOrgano system was used to connect multiple heart chips in series with excellent cell viability and spontaneously physiological beat rates. PMID:26440672

Multi-Scale Models for the Scale Interaction of Organized Tropical Convection

NASA Astrophysics Data System (ADS)

Yang, Qiu

Assessing the upscale impact of organized tropical convection from small spatial and temporal scales is a research imperative, not only for having a better understanding of the multi-scale structures of dynamical and convective fields in the tropics, but also for eventually helping in the design of new parameterization strategies to improve the next-generation global climate models. Here self-consistent multi-scale models are derived systematically by following the multi-scale asymptotic methods and used to describe the hierarchical structures of tropical atmospheric flows. The advantages of using these multi-scale models lie in isolating the essential components of multi-scale interaction and providing assessment of the upscale impact of the small-scale fluctuations onto the large-scale mean flow through eddy flux divergences of momentum and temperature in a transparent fashion. Specifically, this thesis includes three research projects about multi-scale interaction of organized tropical convection, involving tropical flows at different scaling regimes and utilizing different multi-scale models correspondingly. Inspired by the observed variability of tropical convection on multiple temporal scales, including daily and intraseasonal time scales, the goal of the first project is to assess the intraseasonal impact of the diurnal cycle on the planetary-scale circulation such as the Hadley cell. As an extension of the first project, the goal of the second project is to assess the intraseasonal impact of the diurnal cycle over the Maritime Continent on the Madden-Julian Oscillation. In the third project, the goals are to simulate the baroclinic aspects of the ITCZ breakdown and assess its upscale impact on the planetary-scale circulation over the eastern Pacific. These simple multi-scale models should be useful to understand the scale interaction of organized tropical convection and help improve the parameterization of unresolved processes in global climate models.

The Impact of the Demand for Integration in the Large Multi-Business Unit Firm on the IT Organization Structure

ERIC Educational Resources Information Center

Larson, Eric Christopher

2012-01-01

Large, multi-business unit firms are decentralizing their overall corporate structures. At the same time, the structures of their IT organizations are becoming more centralized. This is contrary to current wisdom that the IT organization structure will mimic the structure of the corporation, all else being equal. Because the general business…

What's the Difference Between Vocal Cord Dysfunction and Asthma?

MedlinePlus

... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does not ...

Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery

NASA Astrophysics Data System (ADS)

Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.

2000-02-01

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.

The response of the host microcirculation to bacterial sepsis: does the pathogen matter?

PubMed

Legrand, Matthieu; Klijn, Eva; Payen, Didier; Ince, Can

2010-02-01

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte-endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis.

The Paradox of Mitochondrial Dysfunction and Extended Longevity

PubMed Central

Munkácsy, Erin; Rea, Shane L.

2014-01-01

Mitochondria play numerous, essential roles in the life of eukaryotes. Disruption of mitochondrial function in humans is often pathological or even lethal. Surprisingly, in some organisms mitochondrial dysfunction can result in life extension. This paradox has been studied most extensively in the long-lived Mit mutants of the nematode Caenorhabditis elegans. In this review, we explore the major responses that are activated following mitochondrial dysfunction in these animals and how these responses potentially act to extend their life. We focus our attention on five broad areas of current research – reactive oxygen species signaling, the mitochondrial unfolded protein response, autophagy, metabolic adaptation, and the roles played by various transcription factors. Lastly, we also examine why disruption of complexes I and II differ in their ability to induce the Mit phenotype and extend lifespan. PMID:24699406

Effects of gabexate mesilate on coagulopathy and organ dysfunction in rats with endotoxemia: a potential use of thrombelastography in endotoxin-induced sepsis.

PubMed

Tsai, Hsin-Jung; Ding, Chen; Tsao, Cheng-Ming; Liao, Mei-Hui; Ka, Shuk-Man; Liaw, Wen-Jinn; Wu, Chin-Chen

2015-03-01

Sepsis and its associated multiple organ failure are related to high mortality in critical patients. Several studies have reported that gabexate mesilate, a synthetic inhibitor of trypsin-like serine protease, protects tissues/organs against injury in the models of endotoxemia. The aim of this study was to examine whether gabexate mesilate could attenuate coagulopathy and organ dysfunction in lipopolysaccharide (LPS)-induced sepsis model by using thrombelastography (TEG). LPS (7.5  mg/kg/h, intravenouly for 4  h) was administered to male adult Wistar rats. Some of the LPS rats received a continuous infusion of gabexate mesilate (10  mg/kg/h, intravenously for 8.5  h) for 30  min before the LPS administration. Variable parameters of hemodynamics, biochemistry, hemostasis and inflammatory response were measured for 6  h after the LPS infusion. TEG variables (R-time, K-time, α-angle, and maximal amplitude) were also measured. The pretreatment of LPS rats with gabexate mesilate significantly attenuated the lung, liver and kidney dysfunction, consumptive coagulopathy, the increases in serum tumor necrosis factor-α, interleukin-6, plasma thrombin-antithrombin complex and plasminogen activator inhibitor-1, and neutrophils infiltration score in lung, liver and kidney, compared with the LPS alone group. In addition, TEG parameters correlated with tissue and liver injury in the late phase of endotoxemia. In particular, a strong negative correlation between maximal amplitude at 4  h and Ln (lactate dehydrogenase) at 6  h after LPS infusion was noted (r = -0.752, P < 0.001, R = 0.566). These results indicate that beneficial effects of anticoagulants (e.g. gabexate mesilate) in endotoxemia could be monitored by TEG per se.

Epidemiology and outcome analysis of sepsis and organ dysfunction/failure after burns.

PubMed

Belba, Monika Kristaq; Petrela, Elizana Ylber; Belba, Amy Gjergji

2017-09-01

The aim of this prospective study in adult population is to give frequency data (prevalence, incidence) of burn wound sepsis and its consequences (organ dysfunction/failure); to analyze the evolution of the SOFA cumulative score during the disease and relationship between the SOFA score in the 3rd, 7th, 14th and 21th day after burn with mortality. A prospective cohort study was performed among adult patients (age ≥20 years) admitted in the ICU, with major and moderate burns. Sepsis, organ dysfunction, organ failure and mortality were calculated as Cumulative Incidence (CI) and as Incidence rate (IR). Data from patients with sepsis were compared with those without sepsis. Evaluation of SOFA evolution was done with delta score and the influence of the SOFA score in mortality was calculated with AUC of the ROC curve. Period prevalence of sepsis in our adult burned population was 26%. Incidence proportion as CI was 0.3 or 30 patients per 100 adults. Incidence rate (IR) was 6 patients with sepsis per 100 patient-years. Overall morbidity was 88.1% while overall mortality was 11.9%. Mortality in patients with sepsis was 34.4%. Incidence of MOD was 63% while incidence of MOF was 37%. Respective mortality as CI was 7% and 81% while mortality rate as IR was 1.4 per 100 patient-years in patients with MOD and 16.2 per 100 patient-years in patients with MOF. SOFA-3 should be considered a "reliable indicator" at separating survivors from non survivors and SOFA 7, 14, and 21 should be considered excellent in predicting mortality. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Sex and menopausal status influence human dietary requirements for the nutrient choline.

PubMed

Fischer, Leslie M; daCosta, Kerry Ann; Kwock, Lester; Stewart, Paul W; Lu, Tsui-Shan; Stabler, Sally P; Allen, Robert H; Zeisel, Steven H

2007-05-01

Although humans require dietary choline for methyl donation, membrane function, and neurotransmission, choline can also be derived from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen. A recommended Adequate Intake (AI) exists for choline; however, an Estimated Average Requirement has not been set because of a lack of sufficient human data. The objective of the study was to evaluate the dietary requirements for choline in healthy men and women and to investigate the clinical sequelae of choline deficiency. Fifty-seven adult subjects (26 men, 16 premenopausal women, 15 postmenopausal women) were fed a diet containing 550 mg choline x 70 kg(-1) x d(-1) for 10 d followed by <50 mg choline x 70 kg(-1) x d(-1) with or without a folic acid supplement (400 microg/d per randomization) for up to 42 d. Subjects who developed organ dysfunction during this diet had normal organ function restored after incremental amounts of choline were added back to the diet. Blood and urine were monitored for signs of toxicity and metabolite concentrations, and liver fat was assessed by using magnetic resonance imaging. When deprived of dietary choline, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage, whereas only 44% of premenopausal women developed such signs of organ dysfunction. Moreover, 6 men developed these signs while consuming 550 mg choline x 70 kg(-1) x d(-1), the AI for choline. Folic acid supplementation did not alter the subjects' response. Subject characteristics (eg, menopausal status) modulated the dietary requirement for choline, and a daily intake at the current AI was not sufficient to prevent organ dysfunction in 19 of the subjects.

Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction

PubMed Central

O'Mahony, D Shane; Liles, W Conrad; Altemeier, William A; Dhanireddy, Shireesha; Frevert, Charles W; Liggitt, Denny; Martin, Thomas R; Matute-Bello, Gustavo

2006-01-01

Introduction Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. Methods We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 μg/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). Results Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-α. Conclusion Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury. PMID:16995930

Sex and menopausal status influence human dietary requirements for the nutrient choline2

PubMed Central

Fischer, Leslie M; daCosta, Kerry Ann; Kwock, Lester; Stewart, Paul W; Lu, Tsui-Shan; Stabler, Sally P; Allen, Robert H; Zeisel, Steven H

2008-01-01

Background Although humans require dietary choline for methyl donation, membrane function, and neurotransmission, choline can also be derived from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen. A recommended Adequate Intake (AI) exists for choline; however, an Estimated Average Requirement has not been set because of a lack of sufficient human data. Objective The objective of the study was to evaluate the dietary requirements for choline in healthy men and women and to investigate the clinical sequelae of choline deficiency. Design Fifty-seven adult subjects (26 men, 16 premenopausal women, 15 postmenopausal women) were fed a diet containing 550 mg choline · 70 kg−1 · d−1 for 10 d followed by <50 mg choline · 70 kg−1 · d−1 with or without a folic acid supplement (400 μg/d per randomization) for up to 42 d. Subjects who developed organ dysfunction during this diet had normal organ function restored after incremental amounts of choline were added back to the diet. Blood and urine were monitored for signs of toxicity and metabolite concentrations, and liver fat was assessed by using magnetic resonance imaging. Results When deprived of dietary choline, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage, whereas only 44% of premenopausal women developed such signs of organ dysfunction. Moreover, 6 men developed these signs while consuming 550 mg choline · 70 kg−1 · d−1, the AI for choline. Folic acid supplementation did not alter the subjects’ response. Conclusion Subject characteristics (eg, menopausal status) modulated the dietary requirement for choline, and a daily intake at the current AI was not sufficient to prevent organ dysfunction in 19 of the subjects. PMID:17490963

Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.

PubMed

Estenssoro, Elisa; Kanoore Edul, Vanina S; Loudet, Cecilia I; Osatnik, Javier; Ríos, Fernando G; Vázquez, Daniela N; Pozo, Mario O; Lattanzio, Bernardo; Pálizas, Fernando; Klein, Francisco; Piezny, Damián; Rubatto Birri, Paolo N; Tuhay, Graciela; Díaz, Anatilde; Santamaría, Analía; Zakalik, Graciela; Dubin, Arnaldo

2018-05-08

The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. Cohort study of 3-month duration beginning on July 1, 2016. Forty-nine ICUs. Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. None. Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48-0.55) and 0.74 (0.69-0.77), respectively (p = 0.000). Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy-contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions.

Performance of the PEdiatric Logistic Organ Dysfunction-2 score in critically ill children requiring plasma transfusions.

PubMed

Karam, Oliver; Demaret, Pierre; Duhamel, Alain; Shefler, Alison; Spinella, Philip C; Stanworth, Simon J; Tucci, Marisa; Leteurtre, Stéphane

2016-12-01

Organ dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration, allowing to describe the clinical outcome of critically ill children throughout their stay. This score is increasingly used in clinical trials in specific subpopulation. Our objective was to assess the performance of the PELOD-2 score in a subpopulation of critically ill children requiring plasma transfusions. This was an ancillary study of a prospective observational study on plasma transfusions over a 6-week period, in 101 PICUs in 21 countries. All critically ill children who received at least one plasma transfusion during the observation period were included. PELOD-2 scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion. Performance of the score was assessed by the determination of the discrimination (area under the ROC curve: AUC) and the calibration (Hosmer-Lemeshow test). Four hundred and forty-three patients were enrolled in the study (median age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was 26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71-0.81) and the Hosmer-Lemeshow test was p = 0.76. The serial evaluation of the changes in the daily PELOD-2 scores from day 1 demonstrated a significant association with death, adjusted for the PELOD-2 score on day 1. In a subpopulation of critically ill children requiring plasma transfusion, the PELOD-2 score has a lower but acceptable discrimination than in an entire population. This score should therefore be used cautiously in this specific subpopulation.

Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Hirayama, Masatoshi; Ogawa, Miho; Oshima, Masamitsu; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Ikeda, Kazutaka; Shimmura, Shigeto; Kawakita, Tetsuya; Tsubota, Kazuo; Tsuji, Takashi

2013-01-01

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion. Dry-eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye diseases that cause corneal epithelial damage and results in significant loss of vision and a reduction in the quality of life. Here we demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germs and harderian gland germs both develop in vivo and achieve sufficient physiological functionality, including tear production in response to nervous stimulation and ocular surface protection. This study demonstrates the potential for bioengineered organ replacement to functionally restore the lacrimal gland. PMID:24084941

The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness

PubMed Central

Klingensmith, Nathan J.; Coopersmith, Craig M.

2015-01-01

Synopsis All elements of the gut – the epithelium, the immune system, and the microbiome – are impacted by critical illness and can, in turn, propagate a pathologic host response leading to multiple organ dysfunction syndrome. Preclinical studies have demonstrated that this can occur by release of toxic gut-derived substances into the mesenteric lymph where they can cause distant damage. Further, intestinal integrity is compromised in critical illness with increases in apoptosis and permeability. There is also increasing recognition that microbes alter their behavior and can become virulent based upon host environmental cues. Gut failure is common in critically ill patients; however, therapeutics targeting the gut have proven to be challenging to implement at the bedside. Numerous strategies to manipulate the microbiome have recently been used with varying success in the ICU. PMID:27016162

The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness.

PubMed

Klingensmith, Nathan J; Coopersmith, Craig M

2016-04-01

All elements of the gut - the epithelium, the immune system, and the microbiome - are impacted by critical illness and can, in turn, propagate a pathologic host response leading to multiple organ dysfunction syndrome. Preclinical studies have demonstrated that this can occur by release of toxic gut-derived substances into the mesenteric lymph where they can cause distant damage. Further, intestinal integrity is compromised in critical illness with increases in apoptosis and permeability. There is also increasing recognition that microbes alter their behavior and can become virulent based upon host environmental cues. Gut failure is common in critically ill patients; however, therapeutics targeting the gut have proven to be challenging to implement at the bedside. Numerous strategies to manipulate the microbiome have recently been used with varying success in the ICU. Copyright © 2016 Elsevier Inc. All rights reserved.

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies

PubMed Central

Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Wardenburg, Juliane Bubeck; Fortenberry, James; Zajicek, Anne; Typpo, Katri

2016-01-01

Objective To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome (MODS) presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Data Sources Literature review, research data, and expert opinion. Study Selection Not applicable. Data Extraction Moderated by an expert from the field, issues relevant to the association of MODS with a variety of conditions were presented, discussed and debated with a focus on identifying knowledge gaps and research priorities. Data Synthesis Summary of presentations and discussion supported and supplemented by relevant literature. Conclusions Among critically ill children, MODS is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this manuscript, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of MODS. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anti-cytokine therapies, anti-toxin treatments, anti-oxidant approaches and multiple forms of exogenous steroids. For the field to advance, these and other therapies must be assessed in rigorous manner and implemented accordingly. PMID:28248836

Adolescent Fatigue, POTS, and Recovery: A Guide for Clinicians

PubMed Central

Kizilbash, Sarah J.; Ahrens, Shelley P.; Bruce, Barbara K.; Chelimsky, Gisela; Driscoll, Sherilyn W.; Harbeck-Weber, Cynthia; Lloyd, Robin M.; Mack, Kenneth J.; Nelson, Dawn E.; Ninis, Nelly; Pianosi, Paolo T.; Stewart, Julian M.; Weiss, Karen E.; Fischer, Philip R.

2018-01-01

Many teenagers who struggle with chronic fatigue have symptoms suggestive of autonomic dysfunction that may include lightheadedness, headaches, palpitations, nausea, and abdominal pain. Inadequate sleep habits and psychological conditions can contribute to fatigue, as can concurrent medical conditions. One type of autonomic dysfunction, postural orthostatic tachycardia syndrome, is increasingly being identified in adolescents with its constellation of fatigue, orthostatic intolerance, and excessive postural tachycardia (more than 40 beats/min). A family-based approach to care with support from a multidisciplinary team can diagnose, treat, educate, and encourage patients. Full recovery is possible with multi-faceted treatment. The daily treatment plan should consist of increased fluid and salt intake, aerobic exercise, and regular sleep and meal schedules; some medications can be helpful. Psychological support is critical and often includes biobehavioral strategies and cognitive–behavioral therapy to help with symptom management. More intensive recovery plans can be implemented when necessary. PMID:24819031

Mental health of adolescents who abuse psychoactive substances in Enugu, Nigeria - a cross-sectional study.

PubMed

Igwe, Wilson C; Ojinnaka, Ngozi C

2010-08-10

Association between psychiatric morbidity and substance abuse among adolescent has been reported. However prevalence and pattern of such dysfunctions are unknown in our environment. To determine the prevalence of psychosocial dysfunction and depressive symptoms among adolescents who abuse substance and also note the influence of socio-demographic factors and type of substance on the pattern of dysfunction. A cross-sectional study was carried out among 900 adolescents selected from 29 secondary schools in Enugu metropolis. A multi-stage sampling procedure was used to select the students. The student drug use questionnaire was used to screen respondents for substance abuse. Those who were abusing substance and matched controls (non substance abusers) were assessed for psychiatric symptoms using the 35-item Paediatric Symptom Checklist (PSC) and the Zung Self-rating Depression Scale (SDS). Social classification was done using the parental educational attainment and occupation. A total of 290 students were current substance abusers. The substances most commonly abused were alcohol (31.6%), cola nitida (kola nut) (20.7%) and coffee (15.7%). Using the PSC scale, 70 (24.1%) subjects compared to 29 (10.7%) of the controls had scores in the morbidity range of >or= 28 for psychosocial dysfunction. This was statistically significant (chi(2) = 17.57 p = 0.001). Fifty-four subjects (18.6%) had scores in the morbidity range of >or= 50 for depressive symptoms using the Zung SDS compared to 21 (7.7%) of controls. This was statistically significant (chi(2) = 14.43, p = 0.001). Prevalence of dysfunction was not significantly related to age in both subjects and controls (chi(2) = 4.62, p = 0.010, chi(2) = 4.8, p = 0.10 respectively). Also using both scales, there was no significant relationship between psychosocial dysfunction and gender or social class in both subjects and control. The prevalence of dysfunction using both scales was significantly higher in multiple abusers compared to single abusers. Subjects abusing alcohol scored more on both scales compared to those abusing other substances. Prevalence of psychosocial dysfunction is higher in adolescents abusing substance compare to controls. The prevalence of psychiatric morbidity was not related to the age, gender or social classes in the study population.We advocate periodic screening of our adolescents for drug abuse regular evaluation of such group for possible psychopathology.

Novel clinical features of nonconvulsive status epilepticus

PubMed Central

Nagayama, Masao; Yang, Sunghoon; Geocadin, Romergryko G.; Kaplan, Peter W.; Hoshiyama, Eisei; Shiromaru-Sugimoto, Azusa; Kawamura, Mitsuru

2017-01-01

Nonconvulsive status epilepticus (NCSE) has rapidly expanded from classical features such as staring, repetitive blinking, chewing, swallowing, and automatism to include coma, prolonged apnea, cardiac arrest, dementia, and higher brain dysfunction, which were demonstrated mainly after the 2000s by us and other groups. This review details novel clinical features of NCSE as a manifestation of epilepsy, but one that is underdiagnosed, with the best available evidence. Also, we describe the new concept of epilepsy-related organ dysfunction (Epi-ROD) and a novel electrode and headset which enables prompt electroencephalography. PMID:28979770

Psychogenic erectile dysfunction.

PubMed

Bodie, Joshua A; Beeman, William W; Monga, Manoj

2003-01-01

To educate healthcare professionals on the historical aspects, clinical diagnosis, and current treatment methods of psychogenic erectile dysfunction. A topic review of current literature was performed. Chief sources included primarily mainstream journals in the fields of urology, psychiatry/psychology, impotence/erectile dysfunction, epidemiology, and internal medicine. MEDLINE and PsycINFO databases were utilized. Data from clinical studies, trials, and review articles concerned primarily with psychological aspects of the arousal (erectile function) phase of the male sexual response cycle were collected, analyzed, and summarized in this review article. There has been a shift in how erectile dysfunction has been perceived and treated over the past 30 years. With the current focus now on the very prevalent organic causes of ED, psychological factors are increasingly overlooked, though they remain important to the treatment of the patient as a whole. This article provides a complete, concise review of the interplay between psychological components and erectile function, reviews the work-up and diagnosis of psychogenic ED, and discusses treatment methods. Erectile dysfunction is a prevalent problem that can affect, and can be affected by, psychosocial aspects of a man's life. Medical or pharmacological interventions are often appropriate to treat ED, but the psychosocial aspects should not be ignored. It has become easier for practitioners to put aside patients' psychosocial and interpersonal concerns regarding sexual health. Clinicians provide the best possible treatment if they recognize that erectile dysfunction is a complex, multifactorial disorder, and treat accordingly.

A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

PubMed

Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

2016-06-01

Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Associations and costs of parental symptoms of psychiatric distress in a multi-diagnosis group of children with special needs.

PubMed

Thurston, S; Paul, L; Loney, P; Ye, C; Wong, M; Browne, G

2011-03-01

Families supporting children with complex needs are significantly more distressed and economically disadvantaged than families of children without disability and delay. What is not known is the associations and costs of parental psychiatric distress within a multi-diagnosis group of special needs children. In this cross-sectional survey, families were identified from the Children's Treatment Network. Families were eligible if the child was aged 0-19 years, resided in Simcoe/York, and if there were multiple family needs (n = 429). Some 42% of surveyed parents exhibited symptoms (mild to severe) of psychiatric distress. The presence of these symptoms was associated with reports of poorer social support, family dysfunction, greater adverse impact of the child's situation on the family, poorer child behaviour, unfavourable parenting styles and poorer child psychosocial functioning. The severity of the child's physical dysfunction was not related to parents/guardians most knowledgeable symptoms of psychiatric distress. Total parent costs were higher and children's uses of primary care services were higher in parents with symptoms of psychiatric distress. Parent symptoms of psychiatric distress are a significant societal concern in families with complex needs children. Children's rehabilitation efforts need to incorporate parental mental health assessment and treatment into existing programmes. This could lead to decreases in direct and indirect healthcare utilisation costs. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Restoring effective sleep tranquility (REST): A feasibility and pilot study.

PubMed

Eakman, Aaron M; Schmid, Arlene A; Henry, Kimberly L; Rolle, Natalie R; Schelly, Catherine; Pott, Christine E; Burns, Joshua E

2017-06-01

The purpose of this pilot study was to establish the feasibility of completing a future controlled trial of a multi-component cognitive behavioral therapy for insomnia program for military veterans with sleep disturbance. This was a single-arm feasibility and pilot study. Participants were United States post-9/11 veterans with service-connected injuries, university students, and had self-reported sleep disturbances. Restoring Effective Sleep Tranquility was a multi-component cognitive behavioral therapy for insomnia intervention consisting of seven sessions of group therapy and eight 1:1 sessions delivered by occupational therapists. Feasibility and pilot indicators were process, resources, management, and scientific, including pre-post-assessments of sleep difficulties, dysfunctional sleep beliefs, participation, and pain interference. Indicators were supportive of feasibility, including reduced sleep difficulties (for example Medical Outcomes Study Sleep Measure [ t  = 3.29, p  = .02]), reduced nightmares: t  = 2.79, p  = .03; fewer dysfunctional sleep beliefs: t  = 3.63, p  = .01, and greater ability to participate in social roles: t  = -2.86, p  = .03, along with trends towards improved satisfaction with participation and reduced pain interference. The Restoring Effective Sleep Tranquility program may reduce sleep difficulties and improve participation in US veterans with service-connected injuries, and evidence indicates a controlled trial would be feasible to deliver.

Restoring effective sleep tranquility (REST): A feasibility and pilot study

PubMed Central

Schmid, Arlene A; Henry, Kimberly L; Rolle, Natalie R; Schelly, Catherine; Pott, Christine E; Burns, Joshua E

2017-01-01

Introduction The purpose of this pilot study was to establish the feasibility of completing a future controlled trial of a multi-component cognitive behavioral therapy for insomnia program for military veterans with sleep disturbance. Method This was a single-arm feasibility and pilot study. Participants were United States post-9/11 veterans with service-connected injuries, university students, and had self-reported sleep disturbances. Restoring Effective Sleep Tranquility was a multi-component cognitive behavioral therapy for insomnia intervention consisting of seven sessions of group therapy and eight 1:1 sessions delivered by occupational therapists. Feasibility and pilot indicators were process, resources, management, and scientific, including pre–post-assessments of sleep difficulties, dysfunctional sleep beliefs, participation, and pain interference. Findings Indicators were supportive of feasibility, including reduced sleep difficulties (for example Medical Outcomes Study Sleep Measure [t = 3.29, p = .02]), reduced nightmares: t = 2.79, p = .03; fewer dysfunctional sleep beliefs: t = 3.63, p = .01, and greater ability to participate in social roles: t = –2.86, p = .03, along with trends towards improved satisfaction with participation and reduced pain interference. Conclusion The Restoring Effective Sleep Tranquility program may reduce sleep difficulties and improve participation in US veterans with service-connected injuries, and evidence indicates a controlled trial would be feasible to deliver. PMID:28626295

After the bomb drops: A new look at radiation-induced multiple organ dysfunction syndrome (MODS)

PubMed Central

Williams, Jacqueline P.; McBride, William H.

2012-01-01

Purpose There is increasing concern that, since the Cold War era, there has been little progress regarding the availability of medical countermeasures in the event of either a radiological or nuclear incident. Fortunately, since much is known about the acute consequences that are likely to be experienced by an exposed population, the probability of survival from the immediate hematological crises after total body irradiation (TBI) has improved in recent years. Therefore focus has begun to shift towards later down-stream effects, seen in such organs as the gastrointestinal tract (GI), skin, and lung. However, the mechanisms underlying therapy-related normal tissue late effects, resulting from localised irradiation, have remained somewhat elusive and even less is known about the development of the delayed syndrome seen in the context of whole body exposures, when it is likely that systemic perturbations may alter tissue microenvironments and homeostasis. Conclusions The sequence of organ failures observed after near-lethal TBI doses are similar in many ways to that of multiple organ dysfunction syndrome (MODS), leading to multiple organ failure (MOF). In this review, we compare the mechanistic pathways that underlie both MODS and delayed normal tissue effects since these may impact on strategies to identify radiation countermeasures. PMID:21417595

Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

PubMed

Arbour, Richard B

2013-01-01

Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological criteria. These processes begin far earlier in the continuum of injury, at the moment of terminal brain stem herniation. As such, aggressive, mechanism-based care, including hormonal replacement therapy, becomes clinically appropriate before formal brain death declaration to support cardiopulmonary stability following terminal brain stem herniation.

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions.

PubMed

Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

2017-03-29

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma.

PubMed

Ho, Evangeline S Q; Barrett, Sarah A; Mullaney, Laura M

2017-08-01

Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI) delivers significant dose to surrounding normal tissue (NT). Research into pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of exploiting the potential to reduce NT dose and associated post-treatment complications. This review aims to compare treatment outcomes of pediatric medulloblastoma patients between Proton- and Photon-CSI treatments. A search and review of studies published between 1990 and 2016 comparing pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects - normal organ sparing and target coverage; normal organ dysfunction and second malignancy risks - was completed. Fifteen studies were selected for review and the results were directly compared. Proton-CSI reported improved out-of-field organ sparing while target coverage improvements were inconsistent. Normal organ dysfunction risks were predicted to be lower following Proton-CSI. Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on several different risk models. Proton-CSI conferred better treatment outcomes than Photon-CSI for pediatric medulloblastoma patients. This review serves to compare the current literature in the absence of long-term data from prospective studies.

Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

PubMed Central

Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

2010-01-01

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

PubMed Central

Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

2017-01-01

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption. PMID:28353649

[Quality of life in women with pelvic floor dysfunction].

PubMed

Segedi, Ljiljana Mladenović; Ilić, Katarina Parezanović; Curcić, Aleksandar; Visnjevac, Nemanja

2011-11-01

Pelvic floor dysfunction is a frequent problem affecting more than 50% of women in peri- and postmenopause. Considering that ageing and menopause befall in the significant factors causing this issue, as well as the expected longevity of women in the world and in our country, pelvic floor dysfunction prevelence is foreseen to be even higher. The aim of the study was to evaluate impact of the symptoms of pelvic dysfunction on quality of life and examine body image satisfaction in adult women with pelvic organ prolapse presenting to tertiary care clinic for surgical treatment. This prospective case-control study included 50 patients who presented to tertiary care gynecology clinic for surgical treatment and 50 controls with normal pelvic floor support and without urinary incontinence who presented tertiary care gynecology clinic for other reasons. Both, patients and controls, completed two quastionnaires recommended for the evaluation of symptoms (Pelvic floor distress inventory - short forms) and quality of life impact (Pelvic floor impact questionnaire - short form) of pelvic organ prolapse, and Body Image Scale. The patients scored significantly worse on the prolapse, urinary, colorectal scales and overall score of Pelvic floor distress inventory--20 than controls subjects (134.91 vs 78.08; p < 0.01). The patients also measured significant decrease in condition-specific quality of life (89.23 vs 3.1; p < 0.01). They were more likely to feel self-conscious (78% vs 42%; p < 0.01), less likely to feel physically attractive (78% vs 22%; p < 0.01), more likely to have difficulty looking at themselves naked (70% vs 42%; p < 0.01), less likely to feel sexually attractive (64% vs 32%; p < 0.01), and less likely to feel feminine (56% vs 16%; p < 0.05), than controls. There were no differencies in their feeling of dissatisfaction with appearance when dressed, avoiding people because of appereance and overall dissatisfaction with their body. There was a positive correlation between decreased quality of life and body image in women with pelvic dysfunction. Women with pelvic floor dysfunction have decreased quality of life and body image.

Targeting Extracellular Histones with Novel RNA Bio drugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

organ involved in MODS is the lung (referred to as acute respiratory distress syndrome or ARDS). Trauma, smoke inhalation, burns, radiation , severe...and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome (MODS/ARDS) and ALI that can be easily delivered in combat...MODS, the risk of death is 40%. The most common organ involved in MODS is the lungs (referred to as acute respiratory distress syndrome or ARDS

The predictive value of resting heart rate following osmotherapy in brain injury: back to basics.

PubMed

Hasanpour Mir, Mahsa; Yousefshahi, Fardin; Abdollahi, Mohammad; Ahmadi, Arezoo; Nadjafi, Atabak; Mojtahedzadeh, Mojtaba

2012-12-30

The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia.To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS). By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed. After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07). Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury.

Targeting IL-2: an unexpected effect in treating immunological diseases.

PubMed

Ye, Congxiu; Brand, David; Zheng, Song G

2018-01-01

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

Fat Embolism Syndrome After Femur Fracture Fixation: a Case Report

PubMed Central

Akoh, Craig C; Schick, Cameron; Otero, Jesse; Karam, Matthew

2014-01-01

Fat embolism syndrome (FES) is a multi-organ disorder with potentially serious sequelae that is commonly seen in the orthopaedic patient population after femur fractures. The major clinical features of FES include hypoxia, pulmonary dysfunction, mental status changes, petechiae, tachycardia, fever, thrombocytopenia, and anemia. Due to technological advances in supportive care and intramedullary reaming techniques, the incidence of FES has been reported as low as 0.5 percent. Here, we present a rare case of FES with cerebral manifestations. A previously healthy 24-year old nonsmoking male was admitted to our hospital after an unrestrained head-on motor vehicle collision. The patient's injuries included a left olecranon fracture and closed bilateral comminuted midshaft femur fractures. The patient went on to develop cerebral fat embolism syndrome (CFES) twelve hours after immediate bilateral intramedullary nail fixation. His symptoms included unresponsiveness, disconjugate gaze, seizures, respiratory distress, fever, anemia, thrombocytopenia, and visual changes. Head computed tomography and brain magnetic resonance imaging showed pathognomonic white-matter punctate lesions and watershed involvement. With early recognition and supportive therapy and seizure therapy, the patient went on to have complete resolution of symptoms without cognitive sequelae. PMID:25328460

The proteome of methylmalonic acidemia (MMA): the elucidation of altered pathways in patient livers.

PubMed

Caterino, Marianna; Chandler, Randy J; Sloan, Jennifer L; Dorko, Kenneth; Cusmano-Ozog, Kristina; Ingenito, Laura; Strom, Stephen C; Imperlini, Esther; Scolamiero, Emanuela; Venditti, Charles P; Ruoppolo, Margherita

2016-02-01

Methylmalonic acidemia (MMA) is a heterogeneous and severe autosomal recessive inborn error of metabolism most commonly caused by the deficient activity of the vitamin B12 dependent enzyme, methylmalonyl-CoA mutase (MUT). The main treatment for MMA patients is the dietary restriction of propiogenic amino acids and carnitine supplementation. Despite treatment, the prognosis for vitamin B12 non-responsive patients remains poor and is associated with neonatal lethality, persistent morbidity and decreased life expectancy. While multi-organ pathology is a feature of MMA, the liver is severely impacted by mitochondrial dysfunction which likely underlies the metabolic instability experienced by the patients. Liver and/or combined liver/kidney transplantation is therefore sometimes performed in severely affected patients. Using liver specimens from donors and MMA patients undergoing elective liver transplantation collected under a dedicated natural history protocol (clinicaltrials.gov: NCT00078078), we employed proteomics to characterize the liver pathology and impaired hepatic metabolism observed in the patients. Pathway analysis revealed perturbations of enzymes involved in energy metabolism, gluconeogenesis and Krebs cycle anaplerosis. Our findings identify new pathophysiologic and therapeutic targets that could be valuable for designing alternative therapies to alleviate clinical manifestations seen in this disorder.

Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock

NASA Astrophysics Data System (ADS)

Prasad, Karothu Durga; Trinath, Jamma; Biswas, Ansuman; Sekar, Kanagaraj; Balaji, Kithiganahalli N.; Guru Row, Tayur N.

2014-11-01

Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. The c-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression in in vitro and septic shock in vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis.

Ritonavir and disulfiram may be synergistic in lowering active interleukin-18 levels in acute pancreatitis, and thereby hasten recovery.

PubMed

Kast, Richard Eric

2008-05-08

Interleukin-18 (IL-18) is one of the mediators of both pancreas damage and systemic complications like hypotension and multi-organ dysfunction during acute pancreatitis. IL-18 is generated intracellularly from pro-IL-18 by caspase-1 mediated proteolysis. Active caspase-1 itself is generated intracellularly by the action of the inflammasome, autocatalysis and other stimuli. The anti-retroviral drug ritonavir inhibits conversion of inactive pro-caspase-1 to active caspase-1. Since ritonavir is well tolerated in short-term use it may therefore prove useful in treating acute pancreatitis by lowering caspase-1 mediated IL-18 formation and the many inflammatory mediators downstream from that. The alcoholism treatment drug disulfiram has been in continuous use since the 1950s. It likewise has a low risk profile. Disulfiram inhibits several human proteases, among them caspase-1. Given the current morbidity and mortality of pancreatitis, research should be directed to ritonavir and disulfiram as treatment options for illnesses like pancreatitis where excessive IL-18 contributes to pathology. The first clinically used angiotensin converting enzyme inhibitor, captopril, has shown potent caspase-1 inhibiting activity as well and should be investigated in rodent models of human pancreatitis.

A mutation in MT-TW causes a tRNA processing defect and reduced mitochondrial function in a family with Leigh syndrome.

PubMed

Duff, Rachael M; Shearwood, Anne-Marie J; Ermer, Judith; Rossetti, Giulia; Gooding, Rebecca; Richman, Tara R; Balasubramaniam, Shanti; Thorburn, David R; Rackham, Oliver; Lamont, Phillipa J; Filipovska, Aleksandra

2015-11-01

Leigh syndrome (LS) is a progressive mitochondrial neurodegenerative disorder, whose symptoms most commonly include psychomotor delay with regression, lactic acidosis and a failure to thrive. Here we describe three siblings with LS, but with additional manifestations including hypertrophic cardiomyopathy, hepatosplenomegaly, cholestatic hepatitis, and seizures. All three affected siblings were found to be homoplasmic for an m. 5559A>G mutation in the T stem of the mitochondrial DNA-encoded MT-TW by next generation sequencing. The m.5559A>G mutation causes a reduction in the steady state levels of tRNA(Trp) and this decrease likely affects the stability of other mitochondrial RNAs in the patient fibroblasts. We observe accumulation of an unprocessed transcript containing tRNA(Trp), decreased de novo protein synthesis and consequently lowered steady state levels of mitochondrial DNA-encoded proteins that compromise mitochondrial respiration. Our results show that the m.5559A>G mutation at homoplasmic levels causes LS in association with severe multi-organ disease (LS-plus) as a consequence of dysfunctional mitochondrial RNA metabolism. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Medical management of the acute radiation syndrome.

PubMed

López, Mario; Martín, Margarita

2011-07-13

The acute radiation syndrome (ARS) occurs after whole-body or significant partial-body irradiation (typically at a dose of >1 Gy). ARS can involve the hematopoietic, cutaneous, gastrointestinal and the neurovascular organ systems either individually or in combination. There is a correlation between the severity of clinical signs and symptoms of ARS and radiation dose. Radiation induced multi-organ failure (MOF) describes the progressive dysfunction of two or more organ systems over time. Radiation combined injury (RCI) is defined as radiation injury combined with blunt or penetrating trauma, burns, blast, or infection. The classic syndromes are: hematopoietic (doses >2-3 Gy), gastrointestinal (doses 5-12 Gy) and cerebrovascular syndrome (doses 10-20 Gy). There is no possibility to survive after doses >10-12 Gy. The Phases of ARS are-prodromal: 0-2 days from exposure, latent: 2-20 days, and manifest illness: 21-60 days from exposure. Granulocyte-colony stimulating factor (G-CSF) at a dose of 5 μg/kg body weight per day subcutaneously has been recommended as treatment of neutropenia, and antibiotics, antiviral and antifungal agents for prevention or treatment of infections. If taken within the first hours of contamination, stable iodine in the form of nonradioactive potassium iodide (KI) saturates iodine binding sites within the thyroid and inhibits incorporation of radioiodines into the gland. Finally, if severe aplasia persists under cytokines for more than 14 days, the possibility of a hematopoietic stem cell (HSC) transplantation should be evaluated. This review will focus on the clinical aspects of the ARS, using the European triage system (METREPOL) to evaluate the severity of radiation injury, and scoring groups of patients for the general and specific management of the syndrome.

Fabry disease: Review and experience during newborn screening.

PubMed

Hsu, Ting-Rong; Niu, Dau-Ming

2018-05-01

Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD. Copyright © 2017 Elsevier Inc. All rights reserved.

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

PubMed

Meybohm, Patrick; Kohlhaas, Madeline; Stoppe, Christian; Gruenewald, Matthias; Renner, Jochen; Bein, Berthold; Albrecht, Martin; Cremer, Jochen; Coburn, Mark; Schaelte, Gereon; Boening, Andreas; Niemann, Bernd; Sander, Michael; Roesner, Jan; Kletzin, Frank; Mutlak, Haitham; Westphal, Sabine; Laufenberg-Feldmann, Rita; Ferner, Marion; Brandes, Ivo F; Bauer, Martin; Stehr, Sebastian N; Kortgen, Andreas; Wittmann, Maria; Baumgarten, Georg; Meyer-Treschan, Tanja; Kienbaum, Peter; Heringlake, Matthias; Schoen, Julika; Treskatsch, Sascha; Smul, Thorsten; Wolwender, Ewa; Schilling, Thomas; Fuernau, Georg; Bogatsch, Holger; Brosteanu, Oana; Hasenclever, Dirk; Zacharowski, Kai

2018-03-26

Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Associations of Body Mass Index and Physical Activity With Sexual Dysfunction in Breast Cancer Survivors.

PubMed

Paiva, Carlos Eduardo; Rezende, Fabiana Faria; Paiva, Bianca Sakamoto Ribeiro; Mauad, Edmundo Carvalho; Zucca-Matthes, Gustavo; Carneseca, Estela Cristina; Syrjänen, Kari Juhani; Schover, Leslie R

2016-11-01

Sexual dysfunction is a common and distressing consequence of breast cancer (BC) treatment. In the present study, we investigated the sexual functioning of BC patients and its association with women's personal characteristics and cancer treatments. In this cross-sectional study, sexual function was assessed using the Female Sexual Function Index (FSFI). The health-related quality of life (HRQOL) was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and its breast module BR-23. Of the 235 participants approached, 216 participants were included in the study. Of these, 63 patients reported no sexual activity in the last month and thus were analyzed only in relation to the sexual desire domain of FSFI. A total of 154 (71.3 %) patients were classified with hypoactive sexual desire disorder (HSDD). From those patients reporting sexual activity in the last month, 63.3 % (97 out of 153) were classified with sexual dysfunction. Using hierarchical logistic regression, the variance explained (change in R 2 ) by the addition of body mass index (BMI) and mild to moderate physical activity in the prediction models of sexual dysfunction and HSDD were 6.8 and 7.2 %, respectively. Age, BMI, and physical activity were independently associated with sexual dysfunction and HSDD. Additionally, BC patients with sexual dysfunction reported lower scores on global HRQOL, role functioning, and fatigue. Based on our findings, BC survivors should be encouraged to practice regular physical activity and to lose weight in order to avoid sexual dysfunction. However, future clinical trials are needed to confirm these findings.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

PubMed

Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

2013-07-13

Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia.

PubMed

Daulatzai, Mak Adam

2015-01-01

The non-celiac gluten sensitivity (NCGS) is a chronic functional gastrointestinal disorder which is very common world wide. The human gut harbors microbiota which has a wide variety of microbial organisms; they are mainly symbiotic and important for well being. However, "dysbiosis" - i.e. an alteration in normal commensal gut microbiome with an increase in pathogenic microbes, impacts homeostasis/health. Dysbiosis in NCGS causes gut inflammation, diarrhea, constipation, visceral hypersensitivity, abdominal pain, dysfunctional metabolic state, and peripheral immune and neuro-immune communication. Thus, immune-mediated gut and extra-gut dysfunctions, due to gluten sensitivity with comorbid diarrhea, may last for decades. A significant proportion of NCGS patients may chronically consume alcohol, non-steroidal anti-inflammatory drugs, and fatty diet, as well as suffer from various comorbid disorders. The above pathophysiological substrate and dysbiosis are underpinned by dysfunctional bidirectional "Gut-Brain Axis" pathway. Pathogenic gut microbiota is known to upregulate gut- and systemic inflammation (due to lipopolysaccharide from pathogenic bacteria and synthesis of pro-inflammatory cytokines); they enhance energy harvest, cause obesity, insulin resistance, and dysfunctional vago-vagal gut-brain axis. Conceivably, the above cascade of pathology may promote various pathophysiological mechanisms, neuroinflammation, and cognitive dysfunction. Hence, dysbiosis, gut inflammation, and chronic dyshomeostasis are of great clinical relevance. It is argued here that we need to be aware of NCGS and its chronic pathophysiological impact. Therapeutic measures including probiotics, vagus nerve stimulation, antioxidants, alpha 7 nicotinic receptor agonists, and corticotropin-releasing factor receptor 1 antagonist may ameliorate neuroinflammation and oxidative stress in NCGS; they may therefore, prevent cognitive dysfunction and vulnerability to Alzheimer's disease.

Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity of Liver Damage at the Time of Transplantation

PubMed Central

Habib, Shahid; Khan, Khalid; Hsu, Chiu-Hsieh; Meister, Edward; Rana, Abbas; Boyer, Thomas

2017-01-01

Background We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Methods Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Results Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. Conclusions SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated. PMID:28496531

Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water

PubMed Central

Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

2015-01-01

Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury. PMID:26316710

Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water.

PubMed

Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

2015-01-01

Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.

Relationship between hematologic parameters and left ventricular systolic dysfunction in stable patients with multi-vessel coronary artery disease.

PubMed

Doğdu, Orhan; Akpek, Mahmut; Yarlıoğlueş, Mikail; Kalay, Nihat; Ardıç, Idris; Elçik, Deniz; Senarslan, Omer; Kaya, Mehmet Güngör

2012-12-01

Multi-vessel coronary artery disease (MVCAD) has long been recognized as an important predictor of adverse outcomes in patients with chronic stable angina. The aim of this study is to investigate the relationship between hematologic parameters and impairment of left ventricular systolic functions in patients with stable MVCAD. Patients (n=202) with stable angina and MVCAD were included in this study. According to the left ventricle ejection fraction (LVEF) determined by echocardiography, patients were divided into two groups as the preserved group (LVEF >50%) and the impaired group (LVEF <50%). The preserved group consisted of 106 patients and the impaired group consisted of 96 patients. The frequency of diabetes mellitus was significantly higher in the impaired group compared to the preserved group (respectively, 50% vs. 33%, p=0.01). High sensitivity C-reactive protein (hs-CRP) levels and, neutrophil/lymphocyte ratio (N/L ratio) were significantly higher in the impaired group than in the preserved group (3.9±2.4 vs. 7.9±3.8, p<0.001; 2.7±0.7 vs. 3.9±1.2, p<0.001, respectively). There was a significant correlation between LVEF, N/L ratio and hs-CRP; hs-CRP and N/L ratio were positively correlated (r=0.584; p<0.001), and LVEF was negatively correlated with both hs-CRP and N/L ratio (r=-0.48, p<0.001 and r=-0.43, p<0.001, respectively). A N/L ratio >3.0 had 77% sensitivity and 68% specificity in predicting left ventricular dysfunction in patients with stable MVCAD. In multivariate analysis, N/L ratio (OR: 2.456, <95% Cl 2.056-4.166; p<0.001) was an independent predictor of left ventricular dysfunction in stable patients with MVCAD. N/L ratio and hs-CRP, which is inexpensive and easily measurable in the laboratory, is independently associated with impaired LV systolic functions in patients with stable MVCAD.

An anatomical and physiological basis for the cardiovascular autonomic nervous system consequences of sport-related brain injury.

PubMed

La Fountaine, Michael F

2017-11-29

Concussion is defined as a complex pathophysiological process affecting the brain that is induced by the application or transmission of traumatic biomechanical forces to the head. The result of the impact is the onset of transient symptoms that may be experienced for approximately 2weeks in most individuals. However, in some individuals, symptoms may not resolve and persist for a protracted period and a chronic injury ensues. Concussion symptoms are generally characterized by their emergence through changes in affect, cognition, or multi-sensory processes including the visual and vestibular systems. An emerging consequence of concussion is the presence of cardiovascular autonomic nervous system dysfunction that is most apparent through hemodynamic perturbations and provocations. Further interrogation of data that are derived from continuous digital electrocardiograms and/or beat-to-beat blood pressure monitoring often reveal an imbalance of parasympathetic or sympathetic nervous system activity during a provocation after an injury. The disturbance is often greatest early after injury and a resolution of the dysfunction occurs in parallel with other symptoms. The possibility exists that the disturbance may remain if the concussion does not resolve. Unfortunately, there is little evidence in humans to support the etiology for the emergence of this post-injury dysfunction. As such, evidence from experimental models of traumatic brain injury and casual observations from human studies of concussion implicate a transient abnormality of the anatomical structures and functions of the cardiovascular autonomic nervous system. The purpose of this review article is to provide a mechanistic narrative of multi-disciplinary evidence to support the anatomical and physiological basis of cardiovascular autonomic nervous system dysfunction after concussion. The review article will identify the anatomical structures of the autonomic nervous system and propose a theoretical framework to demonstrate the potential effects of concussive head trauma on corresponding outcome measurements. Evidence from experimental models will be used to describe abnormal cellular functions and provide a hypothetical mechanistic basis for the respective responses of the anatomical structures to concussive head trauma. When available, example observations from the human concussion literature will be presented to demonstrate the effects of concussive head trauma that may be related to anomalous activity in the respective anatomical structures of the autonomic nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Beta-Adrenergic Receptor Polymorphisms and Cardiac Graft Function in Potential Organ Donors

PubMed Central

Khush, K.K.; Pawlikowska, L.; Menza, R.L.; Goldstein, B.A.; Hayden, V.; Nguyen, J.; Kim, H.; Poon, A.; Sapru, A.; Matthay, M.A.; Kwok, P.Y.; Young, W.L.; Baxter-Lowe, L.A.; Zaroff, J.G.

2012-01-01

Prior studies have demonstrated associations between β-adrenergic receptor polymorphisms and left ventricular dysfunction—an important cause of allograft non-utilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. 1,043 organ donors managed from 2001-2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg), and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction<50%. The β1AR1165 and β2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 mcg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts. PMID:22994654

[Chronic rejection: Differences and similarities in various solid organ transplants].

PubMed

Suhling, H; Gottlieb, J; Bara, C; Taubert, R; Jäckel, E; Schiffer, M; Bräsen, J H

2016-01-01

In this paper, chronic rejections after transplantation of the lungs, heart, liver, and kidney are described. Chronic allograft dysfunction (CAD) plays an important role in all of these transplantations and has a significant influence on patient survival. The pathophysiological reasons for CAD varies greatly in the various organs.Chronic lung allograft dysfunction (CLAD) is the most important determinant of survival and quality of life after lung transplantation. Diagnosis is based on lung function, especially forced expiratory flow in 1 s (FEV1) decline. Prevention, early detection, and rapid treatment are extremely important. Azithromycin and extracorporeal photopheresis are commonly used for treatment because they usually positively influence the progression of lung remodeling.The expression for chronic rejection of the heart is cardiac allograft vasculopathy (CAV). Immunological and nonimmunological factors are important for its development. Due to limited therapeutic options, prevention is of utmost importance (administration of mTOR inhibitors and minimizing cardiovascular risk factors).The mid- and long-term survival rates after liver transplantation have hardly changed in recent decades, which is an indication of the difficulty in diagnosing chronic graft dysfunction. Chronic ductopenic rejection accounts for a small proportion of late graft dysfunction. Idiopathic posttransplant hepatitis and de novo autoimmune hepatitis are important in addition to recurrence of the underlying disease that led to transplantation.Chronic allograft nephropathy is the result of severe rejection which cumulates in increasing fibrosis with remodeling. The earliest possible diagnosis and therapy is currently the only option. Diagnosis is based on evidence of donor-specific antibodies and histological findings.

4D cone-beam CT reconstruction using multi-organ meshes for sliding motion modeling

NASA Astrophysics Data System (ADS)

Zhong, Zichun; Gu, Xuejun; Mao, Weihua; Wang, Jing

2016-02-01

A simultaneous motion estimation and image reconstruction (SMEIR) strategy was proposed for 4D cone-beam CT (4D-CBCT) reconstruction and showed excellent results in both phantom and lung cancer patient studies. In the original SMEIR algorithm, the deformation vector field (DVF) was defined on voxel grid and estimated by enforcing a global smoothness regularization term on the motion fields. The objective of this work is to improve the computation efficiency and motion estimation accuracy of SMEIR for 4D-CBCT through developing a multi-organ meshing model. Feature-based adaptive meshes were generated to reduce the number of unknowns in the DVF estimation and accurately capture the organ shapes and motion. Additionally, the discontinuity in the motion fields between different organs during respiration was explicitly considered in the multi-organ mesh model. This will help with the accurate visualization and motion estimation of the tumor on the organ boundaries in 4D-CBCT. To further improve the computational efficiency, a GPU-based parallel implementation was designed. The performance of the proposed algorithm was evaluated on a synthetic sliding motion phantom, a 4D NCAT phantom, and four lung cancer patients. The proposed multi-organ mesh based strategy outperformed the conventional Feldkamp-Davis-Kress, iterative total variation minimization, original SMEIR and single meshing method based on both qualitative and quantitative evaluations.

4D cone-beam CT reconstruction using multi-organ meshes for sliding motion modeling.

PubMed

Zhong, Zichun; Gu, Xuejun; Mao, Weihua; Wang, Jing

2016-02-07

A simultaneous motion estimation and image reconstruction (SMEIR) strategy was proposed for 4D cone-beam CT (4D-CBCT) reconstruction and showed excellent results in both phantom and lung cancer patient studies. In the original SMEIR algorithm, the deformation vector field (DVF) was defined on voxel grid and estimated by enforcing a global smoothness regularization term on the motion fields. The objective of this work is to improve the computation efficiency and motion estimation accuracy of SMEIR for 4D-CBCT through developing a multi-organ meshing model. Feature-based adaptive meshes were generated to reduce the number of unknowns in the DVF estimation and accurately capture the organ shapes and motion. Additionally, the discontinuity in the motion fields between different organs during respiration was explicitly considered in the multi-organ mesh model. This will help with the accurate visualization and motion estimation of the tumor on the organ boundaries in 4D-CBCT. To further improve the computational efficiency, a GPU-based parallel implementation was designed. The performance of the proposed algorithm was evaluated on a synthetic sliding motion phantom, a 4D NCAT phantom, and four lung cancer patients. The proposed multi-organ mesh based strategy outperformed the conventional Feldkamp-Davis-Kress, iterative total variation minimization, original SMEIR and single meshing method based on both qualitative and quantitative evaluations.

4D cone-beam CT reconstruction using multi-organ meshes for sliding motion modeling

PubMed Central

Zhong, Zichun; Gu, Xuejun; Mao, Weihua; Wang, Jing

2016-01-01

A simultaneous motion estimation and image reconstruction (SMEIR) strategy was proposed for 4D cone-beam CT (4D-CBCT) reconstruction and showed excellent results in both phantom and lung cancer patient studies. In the original SMEIR algorithm, the deformation vector field (DVF) was defined on voxel grid and estimated by enforcing a global smoothness regularization term on the motion fields. The objective of this work is to improve the computation efficiency and motion estimation accuracy of SMEIR for 4D-CBCT through developing a multi-organ meshing model. Feature-based adaptive meshes were generated to reduce the number of unknowns in the DVF estimation and accurately capture the organ shapes and motion. Additionally, the discontinuity in the motion fields between different organs during respiration was explicitly considered in the multi-organ mesh model. This will help with the accurate visualization and motion estimation of the tumor on the organ boundaries in 4D-CBCT. To further improve the computational efficiency, a GPU-based parallel implementation was designed. The performance of the proposed algorithm was evaluated on a synthetic sliding motion phantom, a 4D NCAT phantom, and four lung cancer patients. The proposed multi-organ mesh based strategy outperformed the conventional Feldkamp–Davis–Kress, iterative total variation minimization, original SMEIR and single meshing method based on both qualitative and quantitative evaluations. PMID:26758496

Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine.

PubMed

Masha, A; Martina, V

2014-01-01

Several metabolic diseases present a high cardiovascular mortality due to endothelial dysfunction consequences. In the last years of the past century, it has come to light that the endothelial cells, previously considered as inert in what regards an eventual secretion activity, play a pivotal role in regulating different aspects of the vascular function (endothelial function). It was clearly demonstrated that the endothelium acts as a real active organ, owning endocrine, paracrine and autocrine modulation activities by means of which it is able to regulate the vascular homeostasis. The present review will investigate the relationship between some metabolic diseases and the endothelial dysfunction and in particular the mechanisms underlying the effects of metabolic pathologies on the endothelium. Furthermore, it will consider the possible therapeutic employment of the N-acetilcysteine in such conditions.

Changes in hemostasis caused by different replacement fluids and outcome in therapeutic plasma exchange in pediatric patients in a retrospective single center study.

PubMed

Witt, Volker; Pichler, Herbert; Beiglboeck, Elisabeth; Kursten, Friedrich; Weidner, Lisa

2017-02-01

Therapeutic plasma exchange (TPE) is a generally accepted and frequently performed procedure for numerous therapeutic indications in adults. Slowly, TPE is also becoming more and more popular in the treatment of pediatric patients. Although, we know that TPE is safe in pediatric patients, the outcome of children treated with TPE is rarely reported. Furthermore, there are only general recommendations regarding the plasma replacement fluid for children and these are adopted from adults. Data concerning outcome and the influence of different types of replacement fluids on hemostasis in children are scarce. We retrospectively evaluated 324 TPE treatments performed in 35 patients between 2008 and 2013 in our level 4 institution for pediatric hematology and oncology. The plasmapheresis procedures were categorized into three groups based on the replacement fluid used. The first group received solvent/detergent-treated (S/D) plasma (70.0% of patients), the second group was administered 5% human albumin (7.7% of patients) and the third group was treated with a combination of human albumin 5% and S/D plasma (22.3% of patients). To assess hemostasis, data on INR, aPTT, fibrinogen and ATIII were collected before and after plasmapheresis from the patients' charts. A modified Multi Organ Dysfunction Syndrome (MODS) Index was used to classify organ failure. Patient outcome, survival rate and adverse events were evaluated. We found a significant increase in the INR by 35.83% and of the aPTT by 18.53% within the human albumin group. The INR and aPTT of patients allocated to the S/D plasma group decreased by 1.58% and 15.77% on average, respectively. The combination group revealed a mild increase of the INR (9.47%), accompanied by a reduction of aPTT (5.97%). Furthermore we found that the survival rate was significantly associated with a MODS Index of <2 (p<0.001). Overall, the number of adverse events was low (1.2%) and none of these were considered life-threatening. Hemostasis could be preserved in a clinically acceptable range for a variety of underlying diseases with SD plasma alone or in combination with human albumin. Based on our results we would recommend practitioners to closely pre-estimate the hemostatic situation before using human albumin alone in critically ill pediatric patients with a limited ability to produce coagulation factors. The outcome of the patients in our collective exprience is correlated to the extent of organ dysfunction. Therefore further controlled studies are highly recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Relationships at Work in Organisations.

ERIC Educational Resources Information Center

Clarkson, Petruska; Shaw, Patricia

1992-01-01

Identifies five types of relationships at work: the unfinished, working alliance, developmental, personal, and transpersonal. For each type, the following are described: contribution to the organization, human motivation, signs of dysfunction, relationship skill needs, and counseling needs. (SK)

Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System

PubMed Central

Rachdaoui, Nadia; Sarkar, Dipak K.

2017-01-01

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body’s most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic–pituitary–adrenal axis, the hypothalamic–pituitary–gonadal axis, the hypothalamic–pituitary–thyroid axis, the hypothalamic–pituitary–growth hormone/insulin-like growth factor-1 axis, and the hypothalamic–posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol’s effects on various components of the endocrine system and their consequences. PMID:28988577

Management of sepsis: a 47-year-old woman with an indwelling intravenous catheter and sepsis.

PubMed

Angus, Derek C

2011-04-13

Severe sepsis is the term used to describe the host response to infection when complicated by acute organ dysfunction. Severe sepsis occurs in more than 750,000 individuals in the United States each year, with a hospital mortality of about 30%. Although the classic presentation is of florid shock with frank hypotension, fever, and elevated white blood cell count, many patients can present with cryptogenic shock (shock without hypotension) with more subtle signs of vital organ compromise. Using the case of Ms C, a 47-year-old woman with short gut syndrome and an indwelling intravenous catheter who developed an episode of severe sepsis secondary to a central line infection, treatment of sepsis is discussed. Management consists of prompt intervention with broad-spectrum antibiotics and fluid resuscitation, even in the absence of hypotension, and institution of a variety of strategies in the emergency setting to prevent development or worsening of vital organ dysfunction. Although advances in understanding the host immune response have fueled considerable interest in immunomodulatory therapy, the role of such agents in clinical practice remains limited and controversial.

Psychological correlates of functional hypothalamic amenorrhea.

PubMed

Marcus, M D; Loucks, T L; Berga, S L

2001-08-01

To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. Clinical research center in an academic medical institution. Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.

Total Artificial Heart as Bridge to Heart Transplantation in Chagas Cardiomyopathy: Case Report.

PubMed

Ruzza, A; Czer, L S C; De Robertis, M; Luthringer, D; Moriguchi, J; Kobashigawa, J; Trento, A; Arabia, F

2016-01-01

Chagas disease (CD) is becoming an increasingly recognized cause of dilated cardiomyopathy outside of Latin America, where it is endemic, due to population shifts and migration. Heart transplantation (HTx) is a therapeutic option for end-stage cardiomyopathy due to CD, but may be considered a relative contraindication due to potential reactivation of the causative organism with immunosuppression therapy. The total artificial heart (TAH) can provide mechanical circulatory support in decompensated patients with severe biventricular dysfunction until the time of HTx, while avoiding immunosuppressive therapy and removing the organ most affected by the causative organism. We report herein a patient with CD and severe biventricular dysfunction, who had mechanical circulatory support with a TAH for more than 6 months, followed by successful orthotopic HTx and treatment with benznidazole for 3 months. The patient had no evidence of recurrent disease in the transplanted heart based on endomyocardial biopsy up to 1 year post-transplantation, and remains alive more than 30 months after insertion of a TAH and 24 months after HTx. Copyright © 2016 Elsevier Inc. All rights reserved.

Systemic Mastocytosis with Smoldering Multiple Myeloma: Report of a Case

PubMed Central

Garcia, Gwenalyn; Ying, Liu; Hurford, Matthew; Odaimi, Marcel

2016-01-01

Systemic mastocytosis (SM) is a disease characterized by a clonal infiltration of mast cells affecting various tissues of the body. It is grouped into six different subtypes according to the World Health Organization classification. It is called indolent systemic mastocytosis (ISM) when there is no evidence of end organ dysfunction, while the presence of end organ dysfunction defines aggressive systemic mastocytosis (ASM). When SM coexists with a clonal hematological disorder, it is classified as systemic mastocytosis with associated clonal hematological nonmast cell lineage disease (SM-AHNMD). Over 80% of SM-AHNMD cases involve disorders of the myeloid cell lines. To our knowledge, there are only 8 reported cases to date of SM associated with a plasma cell disorder. We report a patient with ISM who was found to have concomitant smoldering multiple myeloma. His disease later progressed to ASM. We discuss this rare association between SM and a plasma cell disorder, and potential common pathophysiologic mechanisms linking the two disorders will be reviewed. We also discuss prognostic factors in SM as well as the management options considered during the evolution of the patient's disease. PMID:27293930

[Pharmaconutrition with parenteral selenium in sepsis].

PubMed

Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

2014-04-01

Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Band of Brothers or Dysfunctional Family? A Military Perspective on Coalition Challenges During Stability Operations

DTIC Science & Technology

2011-01-01

vehicle LCT landing craft, tank LO liaison officer LOO line of operation MIS Military Intelligence Service MND (SE) Multi-National Division South East...23, 2000. Their units then fell under the command of the peace- keeping force (PKF) commander, Lt Gen Jaime de los Santos of the Philippines, who was...rather than instantaneous transition of responsibility between his command and the PKF. He suggested to General de los Santos that the UNTAET staff

ATM Heterozygosity and the Development of Radiation-Induced Erectile Dysfunction and Urinary Morbidity Following Radiotherapy for Prostate Cancer

DTIC Science & Technology

2009-02-01

mentors Richard Stock, M.D., and Barry Rosenstein,PhD., regarding the natural history of prostate cancer treated with brachytherapy and the genetics...Supplement 1, 1 November 2007, Page S630 Peters CA, Stone NN, Cesaretti JA and Stock RG “The Effect of Family History on Outcome in Patients Treated...Grimm PD, et al. Centralized multi- institutional postimplant analysis for interstitial prostate brachy- therapy. Int J Radiat Oncol Biol Phys 1998;41:921

Fluoralkenyl nortropanes

DOEpatents

Goodman, Mark M.; Chen, Ping

2002-02-05

Provided are compounds of the following formula: ##STR1## wherein R is C2-C6 mono- or multi-unsaturated hydrocarbon having one or more ethylene, acetylene or allene groups, A is 18 or 19, and X is H or halogen. The compounds of the invention bind to dopamine transporter with high affinity and selectivity and are thus useful as diagnostic and therapeutic agents for diseases associated with dopamine transporter dysfunction. The radiolabeled compounds are useful as imaging agents for visualizing the location and density of dopamine transporter by PET imaging.

[The role of oxidative metabolism disturbance in the development of NO-related endothelial dysfunction during chronic hearth failure].

PubMed

Goishvili, N; Kakauridze, N; Sanikidze, T

2005-05-01

The aim of the work was to establish the oxidative metabolism changes and NO data in Chronic Hearth Failure (HF). 52 patients were included in the investigation, among them 37 patients with CHD and chronic HF (II-IV functional class by NIHA) and 17 without it (control group). For revealing of organism redox-status (ceruloplasmine, Fe3+-transfferine, Mn2+, methemoglobine) the blood paramagnetic centers was studied by electron paramagnetic resonance method. For revealing of blood free NO, the diethyldithiocarbamat (SIGMA) was used. In chronic HF the oxidative process intensification and organism compensate reaction reduction with low Fe3+-transferine levels, increased Mn2++, methaemoglobin and inactivation of erythrocytes membranes adrenergic receptors were revealed. In chronic HF the accumulation of reactive oxygen levels provoke NO transformation in peroxynitrote with following decreases of blood free NO and develop the endothelial dysfunction.

Systemic lupus erythematosus with organic brain syndrome: serial electroencephalograms accurately evaluate therapeutic efficacy.

PubMed

Kato, Takashi; Shiratori, Kyoji; Kobashigawa, Tsuyoshi; Hidaka, Yuji

2006-01-01

A 48-year-old man with systemic lupus erythematosus developed organic brain syndrome. High-dose prednisolone was ineffective, and somnolence without focal signs rapidly developed. Electroencephalogram (EEG) demonstrated a slow basic rhythm (3 Hz), but brain magnetic resonance imaging was normal. Somnolence resolved soon after performing plasma exchange (two sessions). However, memory dysfunction persisted, with EEG demonstrating mild abnormalities (7-8 Hz basic rhythm). Double-filtration plasmapheresis (three sessions) was done, followed by intravenous cyclophosphamide. Immediately after the first plasmapheresis session, memory dysfunction began to improve. After the second dose of cyclophosphamide, intellectual function resolved completely and EEG findings also normalized (basic rhythm of 10 Hz waves). Serial EEG findings precisely reflected the neurological condition and therapeutic efficacy in this patient. In contrast, protein levels in cerebrospinal fluid remained high and did not seem to appropriately reflect the neurological condition in this patient.

Myocardial Ischemia Induces SDF-1α Release in Cardiac Surgery Patients.

PubMed

Kim, Bong-Sung; Jacobs, Denise; Emontzpohl, Christoph; Goetzenich, Andreas; Soppert, Josefin; Jarchow, Mareike; Schindler, Lisa; Averdunk, Luisa; Kraemer, Sandra; Marx, Gernot; Bernhagen, Jürgen; Pallua, Norbert; Schlemmer, Heinz-Peter; Simons, David; Stoppe, Christian

2016-06-01

In the present observational study, we measured serum levels of the chemokine stromal cell-derived factor-1α (SDF-1α) in 100 patients undergoing cardiac surgery with cardiopulmonary bypass at seven distinct time points including preoperative values, myocardial ischemia, reperfusion, and the postoperative course. Myocardial ischemia triggered a marked increase of SDF-1α serum levels whereas cardiac reperfusion had no significant influence. Perioperative SDF-1α serum levels were influenced by patients' characteristics (e.g., age, gender, aspirin intake). In an explorative analysis, we observed an inverse association between SDF-1α serum levels and the incidence of organ dysfunction. In conclusion, time of myocardial ischemia was identified as the key stimulus for a significant upregulation of SDF-1α, indicating its role as a marker of myocardial injury. The inverse association between SDF-1α levels and organ dysfunction association encourages further studies to evaluate its organoprotective properties in cardiac surgery patients.

Mechanisms of Mitochondrial Dysfunction in Autism

DTIC Science & Technology

2013-07-01

The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an...CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: 5f. WORK UNIT...NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING / MONITORING

Psychosexual disorders and dermatologists

PubMed Central

Narang, Tarun; Garima; Singh, Shubh M.

2016-01-01

Sexual problems that are psychological in origin, rather than physiological, are called psychosexual disorders. Multiple factors, such as general health of the patient, chronic illnesses, psychiatric/psychological disorders, and socio-cultural factors, alone or in combination can be attributed to the development of psychosexual dysfunctions. The symptoms of these disorders vary for each individual and differ with gender. These disorders may be categorized as sexual dysfunction, paraphilias, and gender identity disorders. Dermatologists are sometimes consulted for sexual dysfunctions in their routine practice by the patients visiting sexually transmitted infections (STI) clinics because a majority of the patients believe that these problems are caused by dysfunctions in the sex organs, and because people are hesitant to go to sexuality clinics and psychiatrists for such problems. Sometimes these patients are referred from other specialties such as urology or gynecology; most often, we attempt to search for STIs or other dermatoses on the genitalia and refer them back. We often underestimate the prevalence of sexual concerns of the patients or feel uncomfortable discussing matters of sexuality with them. Dermatologists should understand basic sexual medicine and ask patients for sexual problems. They should be trained to manage such patients accordingly. In this review, we will be focusing on sexual dysfunctions, their etiopathogenesis, and management from a dermatologist's perspective. PMID:27294047

Lung-Kidney Cross-Talk in the Critically Ill Patient.

PubMed

Husain-Syed, Faeq; Slutsky, Arthur S; Ronco, Claudio

2016-08-15

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

Vascular rarefaction mediates whitening of brown fat in obesity

PubMed Central

Shimizu, Ippei; Aprahamian, Tamar; Kikuchi, Ryosuke; Shimizu, Ayako; Papanicolaou, Kyriakos N.; MacLauchlan, Susan; Maruyama, Sonomi; Walsh, Kenneth

2014-01-01

Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism. PMID:24713652

Menstrual dysfunction in female athletes. A review for clinicians.

PubMed

Noakes, T D; van Gend, M

1988-03-19

A critical review of factors considered to cause menstrual dysfunction is women athletes with no overt organic cause for the abnormality is presented. Evidence suggests that although regular exercise can produce a specific change in hypothalamic-pituitary function, in particular reduced pulsatile luteinising hormone secretion, this is not associated with amenorrhoea or oligomenorrhoea in the majority of female athletes, most of whom continue to menstruate cyclically. Thus additional factors must be operative. It seems probable that severe menstrual dysfunction occurs in a specific predisposed subset of women athletes who have a particular personality type or body build and are attracted to a lifestyle including regular vigorous exercise. The biochemical basis may be related to hypothalamic, pituitary or even ovarian dysfunction possibly due to elevated levels of anti-reproductive hormones, including beta-endorphins, dopamine, prolactin and catechol oestrogens, induced by exercise; dopamine appears the most likely candidate. Chronic hypo-oestrogenic or eu-oestrogenic amenorrhoea or oligomenorrhoea may not be benign and should probably be treated in order to reduce the risk of osteoporosis or endometrial hyperplasia and adenocarcinoma.

Biomechanics of Cardiac Function

PubMed Central

Voorhees, Andrew P.; Han, Hai-Chao

2015-01-01

The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments. PMID:26426462

Biventricular assist device for scombroid poisoning with refractory myocardial dysfunction: a bridge to recovery.

PubMed

Grinda, Jean-Michel; Bellenfant, Florence; Brivet, François Gilles; Carel, Yvan; Deloche, Alain

2004-09-01

We report the usefulness of biventricular mechanical circulatory support in a 36-yr-old woman with refractory myocardial dysfunction resulting from scombroid poisoning. Case report. Medical and surgical university care units. A previously healthy 36-yr-old woman with severe myocardial dysfunction unresponsive to epinephrine (1.3 microg/kg/min) and dobutamine (18 microg/kg/min) after the ingestion of cooked fresh tuna. Implantation at day 3 of a biventricular assist device consisting of two paracorporeal pneumatic pumps set at 70 beats/min to reach an output of 5.6 L/min during 8 days. The biventricular mechanical circulatory assist device allowed weaning of the inotropic drugs, maintenance of end-organ function, and support of the patient until myocardial recovery. The patient was successfully explanted 11 days after ingestion. Cardiac function had totally recovered, but a stroke was noted. At 3-yrs follow-up, there was no cardiac or neurologic sequela. This report describes severe myocardial dysfunction secondary to scombroid poisoning and demonstrates the usefulness of a mechanical circulatory assist device as a bridge to recovery.

The Immune System’s Role in Sepsis Progression, Resolution and Long-Term Outcome

PubMed Central

Delano, Matthew J.; Ward, Peter A.

2016-01-01

SUMMARY Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. Since so many sepsis survivors succumb later to persistent, recurrent, nosocomial and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality. PMID:27782333

Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction

PubMed Central

Bavli, Danny; Prill, Sebastian; Ezra, Elishai; Levy, Gahl; Cohen, Merav; Vinken, Mathieu; Vanfleteren, Jan; Jaeger, Magnus; Nahmias, Yaakov

2016-01-01

Microfluidic organ-on-a-chip technology aims to replace animal toxicity testing, but thus far has demonstrated few advantages over traditional methods. Mitochondrial dysfunction plays a critical role in the development of chemical and pharmaceutical toxicity, as well as pluripotency and disease processes. However, current methods to evaluate mitochondrial activity still rely on end-point assays, resulting in limited kinetic and prognostic information. Here, we present a liver-on-chip device capable of maintaining human tissue for over a month in vitro under physiological conditions. Mitochondrial respiration was monitored in real time using two-frequency phase modulation of tissue-embedded phosphorescent microprobes. A computer-controlled microfluidic switchboard allowed contiguous electrochemical measurements of glucose and lactate, providing real-time analysis of minute shifts from oxidative phosphorylation to anaerobic glycolysis, an early indication of mitochondrial stress. We quantify the dynamics of cellular adaptation to mitochondrial damage and the resulting redistribution of ATP production during rotenone-induced mitochondrial dysfunction and troglitazone (Rezulin)-induced mitochondrial stress. We show troglitazone shifts metabolic fluxes at concentrations previously regarded as safe, suggesting a mechanism for its observed idiosyncratic effect. Our microfluidic platform reveals the dynamics and strategies of cellular adaptation to mitochondrial damage, a unique advantage of organ-on-chip technology. PMID:27044092

Neuropsychological dysfunction, mood disturbance, and emotional status of munitions workers.

PubMed

Bowler, R M; Lezak, M; Booty, A; Hartney, C; Mergler, D; Levin, J; Zisman, F

2001-01-01

The objective of this study was to compare the neuropsychological function, emotional status, visual function, and illness prevalence of 265 former munitions plant workers (M age = 56.7 years, M years of education = 12.07; 201 African American, 64 White) exposed to organic solvents for an average of 17.03 years with that of a group of 77 unexposed controls (M age = 51.3 years, M years of education = 13.07; 30 African American, 47 White). Neuropsychological tests were selected from the World Health Organization Neurobehavioral Core Test Battery, Wechsler Adult Intelligence Scale-III (WAIS-III), and Wechsler Memory Scale-III (WMS-III) and also included the Brief Symptom Inventory, Profile of Mood States, Beck Anxiety Inventory, and Beck Depression Inventory. Vision tests included the Lanthony d-15 color vision, the Vistech Contrast Sensitivity, and the Snellen. The exposed group showed greater deficits than the controls in verbal learning (WMS-III Logical Memory I Learning Slope and Word Lists I Recall), visuomotor tracking speed (Cancellation H, WAIS-III Digit Symbol-Coding) and psychomotor function (Dynamometer and Grooved Pegboard), and dysfunction in emotional status, illness prevalence, and visual function. African American workers reported higher levels of exposure than Whites. Exposure relations demonstrated increased neuropsychological dysfunction with increased exposure.

Objective vestibular testing of children with dizziness and balance complaints following sports-related concussions.

PubMed

Zhou, Guangwei; Brodsky, Jacob R

2015-06-01

To conduct objective assessment of children with balance and vestibular complaints following sports-related concussions and identify the underlying deficits by analyzing laboratory test outcomes. Case series with chart review. Pediatric tertiary care facility. Medical records were reviewed of 42 pediatric patients with balance and/or vestibular complaints following sports-related concussions who underwent comprehensive laboratory testing on their balance and vestibular function. Patients' characteristics were summarized and results analyzed. More than 90% of the children with protracted dizziness or imbalance following sports-related concussion had at least 1 abnormal finding from the comprehensive balance and vestibular evaluation. The most frequent deficit was found in dynamic visual acuity test, followed by Sensory Organization Test and rotational test. Patient's balance problem associated with concussion seemed to be primarily instigated by vestibular dysfunction. Furthermore, semicircular canal dysfunction was involved more often than dysfunction of otolith organs. Yet, <10% of the children experienced a hearing loss following sports-related concussion. Vestibular impairment is common among children with protracted dizziness or imbalance following sports-related concussion. Our study demonstrated that proper and thorough evaluation is imperative to identify these underlying deficits and laboratory tests were helpful in the diagnosis and recommendation of following rehabilitations. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Complications of Transfusion-Dependent β-Thalassemia Patients in Sistan and Baluchistan, South-East of Iran.

PubMed

Yaghobi, Maryam; Miri-Moghaddam, Ebrahim; Majid, Naderi; Bazi, Ali; Navidian, Ali; Kalkali, Asiyeh

2017-10-01

Background : Thalassemia syndromes are among prevalent hereditary disorders imposing high expenses on health-care system worldwide and in Iran. Organ failure represents a life-threatening challenge in transfusion- dependent β-thalassemia (TDT) patients. The purpose of the present study was to determine the frequency of organ dysfunctions among TDT patients in Sistan and Baluchistan province in South-East of Iran. Materials and Methods: Laboratory and clinical data were extracted from medical records as well as by interviews. Standard criteria were applied to recognize cardiac, gonadal, endocrine and renal dysfunctions. The collected data were analyzed using the SPSS statistics software (Ver.19). Results: A total of 613 TDT patients (54.3% males and 45.7% females) were included in this study. The mean age of patients was 13.3 ±7.7 years old. Cardiac events comprised the most encountered complications (76.4%), following by hypogonadism (46.8%), parathyroid dysfunction (22%), thyroid abnormalities (8.3%), diabetes (7.8%) and renal disease (1.8%). Hypogonadism comprised the most identified complication in patient <15 years old, while the cardiac complications were the most frequent sequela in patients >15 years old (P<0.01). Conclusion: As cardiac events are significantly more common among TDT patients, close monitoring of the heart function is recommended for identifying patients with cardiac problems.

Comparison of multi-enzyme and thermophilic bacteria on the hydrolysis of mariculture organic waste (MOW).

PubMed

Guo, Liang; Sun, Mei; Zong, Yan; Zhao, Yangguo; Gao, Mengchun; She, Zonglian

2016-01-01

Mariculture organic waste (MOW) is rich in organic matter, which is a potential energy resource for anaerobic digestion. In order to enhance the anaerobic fermentation, the MOW was hydrolyzed by multi-enzyme and thermophilic bacteria. It was advantageous for soluble chemical oxygen demand (SCOD) release at MOW concentrations of 6 and 10 g/L with multi-enzyme and thermophilic bacteria pretreatments. For multi-enzyme, the hydrolysis was not obvious at substrate concentrations of 1 and 3 g/L, and the protein and carbohydrate increased with hydrolysis time at substrate concentrations of 6 and 10 g/L. For thermophilic bacteria, the carbohydrate was first released at 2-4 h and then consumed, and the protein increased with hydrolysis time. The optimal enzyme hydrolysis for MOW was determined by measuring the changes of SCOD, protein, carbohydrate, ammonia and total phosphorus, and comparing with acid and alkaline pretreatments.

Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

PubMed Central

He, Chao; Zhang, Wei; Li, Suobei; Ruan, Wei; Xu, Junmei

2018-01-01

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction. PMID:29765498

[A model of multiple organ injury induced by Klebsiella pneumoniae pneumonia in aged rats].

PubMed

Li, Jian-sheng; Wang, Shou-fu; Qin, Jin-li; Zhang, Hui-jian; Li, Su-yun; Yu, Hai-bin; Wang, Feng; Liu, Si-hua; Li, Ya

2009-04-01

To reproduce a model of bacterial multiple organ injury (MOI) in aged rats. Male Sprague-Dawley (SD) rats were used. The young rats were divided into young control group (YCG, n=10) and young model group (YMG, n=15), and the elderly, aged control group (ACG, n=10) and aged model group (AMG, n=25). The model of rats with Klebsiella pneumoniae pneumonia was produced by tracheal instillation of the bacteria, and injury to various organs was observed and evaluated with changes in biochemical parameters, pathological pictures and mortality. Between YMG and AMG, the mortality rates were 33.33% (5/15) and 60.00% (15/25), respectively, at 24 hours after instillation of the bacteria. Compared with YCG and ACG, the neutrophil percentage and white blood cell (WBC) counts in peripheral blood increased significantly in YMG and AMG groups (all P<0.01), the rates of dysfunction of the lungs, the heart and the liver, were 60%-100%. The respiratory dysfunction was evidenced by an increase in the arterial partial pressure of carbon dioxide (PaCO(2), P<0.01), and a decrease in the arterial partial pressure of oxygen (PaO(2), P<0.05 or P<0.01). Myocardial dysfunction was shown by a the sharp increase in creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH), and that of the liver by changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.05 or P<0.01). The pathological changes under light and electronic microscopy were obvious, and the main feature was infiltration of the inflammatory cells. Compared with YMG, PaO(2) in AMG dropped significantly, PaCO(2) increased, CK, CK-MB, LDH, ALT and AST also increased significantly (P<0.05 or P<0.01). The scores of pathological injury in the lungs, the heart and the small intestine in the AMG were obviously higher than that in YMG group (all P<0.05), and the same was trend in the liver and the kidney. The model of bacterial MOI in aged rats is reproduced successfully, and it mimics the pathogenesis of multiple organ dysfunction syndrome (MODS) which initiates from infection in the lungs. The model is simple and convenient to replicate with a high success rate. The MOI in the aged rats is characterized by the severity of the organ injury and a high mortality rate.

Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy.

PubMed

Yogasundaram, Haran; Kim, Daniel; Oudit, Omar; Thompson, Richard B; Weidemann, Frank; Oudit, Gavin Y

2017-07-01

Anderson-Fabry disease (AFD) is an X-linked recessive, multisystem disease of lysosomal storage. A mutation in the gene encoding the hydrolase enzyme α-galactosidase A results in its deficiency, or complete absence of activity. Subsequent progressive intracellular accumulation of glycosphingolipids, predominantly globotriaosylceramide, in various tissues, results in progressive organ dysfunction and failure, most commonly affecting the kidneys, nervous system, skin, eyes, vascular endothelium, and the heart. Cardiac involvement in AFD represents a leading cause of morbidity and mortality. Globotriaosylceramide accumulation affects cardiomyocytes, smooth muscle cells, vascular endothelial cells, and fibroblasts leading to various pathologies including valvular regurgitation, conduction disease and arrhythmias, coronary microvascular dysfunction, and right and left ventricular hypertrophy (LVH) leading to early diastolic dysfunction and late-stage systolic impairment. Diagnosis is on the basis of decreased plasma α-galactosidase activity in men and positive genetic testing in women. Contemporary large-scale screening studies have revealed a prevalence of 1%-5% in patients with unexplained LVH in multiple cohorts. Cardiac magnetic resonance imaging, with its unique tissue characterization capabilities, is the most important imaging modality to assess for cardiomyopathy in patients with AFD. Enzyme replacement therapy is indicated in AFD patients with significant organ involvement, and has been shown to clear sphingolipids from endothelial cells in other organs, as well as to reduce left ventricular mass as early as 6 months after starting treatment. There is increasing evidence that enzyme replacement therapy might be more effective if given at earlier stages of disease, before the development of LVH and myocardial fibrosis. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Bioengineered silkworms with butterfly cytotoxin-modified silk glands produce sericin cocoons with a utility for a new biomaterial.

PubMed

Otsuki, Ryosuke; Yamamoto, Masafumi; Matsumoto, Erika; Iwamoto, Shin-Ichi; Sezutsu, Hideki; Suzui, Masumi; Takaki, Keiko; Wakabayashi, Keiji; Mori, Hajime; Kotani, Eiji

2017-06-27

Genetically manipulated organisms with dysfunction of specific tissues are crucial for the study of various biological applications and mechanisms. However, the bioengineering of model organisms with tissue-specific dysfunction has not progressed because the challenges of expression of proteins, such as cytotoxins, in living cells of individual organisms need to be overcome first. Here, we report the establishment of a transgenic silkworm ( Bombyx mori ) with posterior silk glands (PSGs) that was designed to express the cabbage butterfly ( Pieris rapae ) cytotoxin pierisin-1A (P1A). P1A, a homolog of the apoptosis inducer pierisin-1, had relatively lower DNA ADP ribosyltransferase activity than pierisin-1; it also induced the repression of certain protein synthesis when expressed in B. mori -derived cultured cells. The transgene-derived P1A domain harboring enzymatic activity was successfully expressed in the transgenic silkworm PSGs. The glands showed no apoptosis-related morphological changes; however, an abnormal appearance was evident. The introduced truncated P1A resulted in the dysfunction of PSGs in that they failed to produce the silk protein fibroin. Cocoons generated by the silkworms solely consisted of the glue-like glycoprotein sericin, from which soluble sericin could be prepared to form hydrogels. Embryonic stem cells could be maintained on the hydrogels in an undifferentiated state and proliferated through stimulation by the cytokines introduced into the hydrogels. Thus, bioengineering with targeted P1A expression successfully produced silkworms with a biologically useful trait that has significant application potential.

Bioengineered silkworms with butterfly cytotoxin-modified silk glands produce sericin cocoons with a utility for a new biomaterial

PubMed Central

Otsuki, Ryosuke; Yamamoto, Masafumi; Matsumoto, Erika; Iwamoto, Shin-ichi; Sezutsu, Hideki; Suzui, Masumi; Takaki, Keiko; Wakabayashi, Keiji; Mori, Hajime; Kotani, Eiji

2017-01-01

Genetically manipulated organisms with dysfunction of specific tissues are crucial for the study of various biological applications and mechanisms. However, the bioengineering of model organisms with tissue-specific dysfunction has not progressed because the challenges of expression of proteins, such as cytotoxins, in living cells of individual organisms need to be overcome first. Here, we report the establishment of a transgenic silkworm (Bombyx mori) with posterior silk glands (PSGs) that was designed to express the cabbage butterfly (Pieris rapae) cytotoxin pierisin-1A (P1A). P1A, a homolog of the apoptosis inducer pierisin-1, had relatively lower DNA ADP ribosyltransferase activity than pierisin-1; it also induced the repression of certain protein synthesis when expressed in B. mori-derived cultured cells. The transgene-derived P1A domain harboring enzymatic activity was successfully expressed in the transgenic silkworm PSGs. The glands showed no apoptosis-related morphological changes; however, an abnormal appearance was evident. The introduced truncated P1A resulted in the dysfunction of PSGs in that they failed to produce the silk protein fibroin. Cocoons generated by the silkworms solely consisted of the glue-like glycoprotein sericin, from which soluble sericin could be prepared to form hydrogels. Embryonic stem cells could be maintained on the hydrogels in an undifferentiated state and proliferated through stimulation by the cytokines introduced into the hydrogels. Thus, bioengineering with targeted P1A expression successfully produced silkworms with a biologically useful trait that has significant application potential. PMID:28607081

RECOMBINANT FACTOR XIII DIMINISHES MULTIPLE ORGAN DYSFUNCTION IN RATS CAUSED BY GUT ISCHEMIA-REPERFUSION INJURY

PubMed Central

Zaets, Sergey B.; Xu, Da-Zhong; Lu, Qi; Feketova, Eleonora; Berezina, Tamara L.; Gruda, Maryann; Malinina, Inga V.; Deitch, Edwin A.; Olsen, Eva H. N.

2010-01-01

Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Because FXIII has also been shown to modulate inflammation and endothelial permeability, we hypothesized that FXIII diminishes multiple organ dysfunction caused by gut I/R injury. A model of superior mesenteric artery occlusion (SMAO) was used to induce gut I/R injury. Rats were subjected to 45-min SMAO or sham SMAO and treated with recombinant human FXIII A2 subunit (rFXIII) or placebo at the beginning of the reperfusion period. Lung permeability, lung and gut myeloperoxidase activity, gut histology, neutrophil respiratory burst, and microvascular blood flow in the liver and muscles were measured after a 3-h reperfusion period. The effect of activated rFXIII on transendothelial resistance of human umbilical vein endothelial cells was tested in vitro. Superior mesenteric artery occlusion–induced lung permeability as well as lung and gut myeloperoxidase activity was significantly lower in rFXIII-treated versus untreated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and ileal mucosal injury. Rats treated with rFXIII also had higher liver microvascular blood flow compared with the placebo group. Superior mesenteric artery occlusion did not cause FXIII consumption during the study period. In vitro, activated rFXIII caused a dose-dependent increase in human umbilical vein endothelial cell monolayer resistance to thrombin-induced injury. Thus, administration of rFXIII diminishes SMAO-induced multiple organ dysfunction in rats, presumably by preservation of endothelial barrier function and the limitation of polymorphonuclear leukocyte activation. PMID:18948851

[Hand motor dysfunctions in computer users].

PubMed

Shavlovskaia, O A; Shvarkov, S B; Posokhov, S I

2010-01-01

It were studied 239 female typists aged from 16 to 62 years (mean age 20,1±7,8 years) using author's questionnaire for computer typists to assess hand function and develop preventive measures of disturbances revealed. Indirect signs of tunnel hand neuropathy (27,2%), focal hand dystonia (21,4%) and muscular-tonic syndromes of different localization (18%) have been found. Typists are a risk group of fine hand motor dysfunctions. As preventive measures, authors recommend to use computer auxiliary devices, to change a motor stereotype during the day, to make hand "motor holidays", to organize working place.

Nonpharmacologic Treatment of Erectile Dysfunction

PubMed Central

Montague, Drogo K

2002-01-01

Nonpharmacologic treatment for erectile dysfunction (ED) includes sex therapy, the use of vacuum erection devices, penile prosthesis implantation, and penile vascular surgery. Sex therapy is indicated for psychogenic ED and is at times a useful adjunct for other treatments in men with mixed psychogenic and organic ED. Vacuum erection devices produce usable erections in over 90% of patients; however, patient and partner acceptability is an issue. Three-piece inflatable penile prostheses create flaccidity and an erection that comes close to that which occurs naturally. Penile vascular surgery has shown greatest efficacy in young men with vasculogenic ED resulting from pelvic or perineal trauma. PMID:16986016

An evaluation of the impact of multi-walled carbon nanotubes on soil microbial community structure and functional diversity

USDA-ARS?s Scientific Manuscript database

Increasing application of carbon nanotubes (CNTs) triggers the need for an assessment of their effects on organisms in the environment. Soil microbial communities play a significant role in soil organic matter dynamics and nutrient cycling. This study evaluated the impacts of multi-walled carbon nan...

Typologies of adverse childhood experiences and their relationship to incarceration in U.S. military veterans.

PubMed

Ross, Jana; Waterhouse-Bradley, Bethany; Contractor, Ateka A; Armour, Cherie

2018-05-01

Numerous studies have reported that adverse childhood experiences (ACEs) are associated with negative psychosocial outcomes in adulthood, but no study has examined the different typologies of ACEs and the relationship of these with adult incarceration in military veterans. The current study used latent class analysis to examine the existence of different childhood maltreatment and household dysfunction typologies in a sample of U.S. military veterans identified through the National Epidemiological Survey on Alcohol and Related Conditions-III ((NESARC-III)). A total of 60.73% of veterans reported one or more ACEs. Four latent classes were identified and were named Low adversities, Moderate maltreatment with high household substance use, Severe maltreatment with moderate household dysfunction and Severe multi-type adversities. Relative to the Low adversities class, the three maltreatment/dysfunction classes had significantly elevated odds ratios (1.72-2.29) for adult incarceration, when controlling for sociodemographic characteristics and alcohol and drug use. The results point to the importance of examining childhood risk factors for incarceration and suggest that a certain sub-group of military personnel who are about to transition into the civilian life may need additional support to adjust and live successful lives. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Female sexual dysfunction: a systematic overview of classification, pathophysiology, diagnosis and treatment].

PubMed

Marthol, H; Hilz, M J

2004-03-01

Sexual dysfunction is defined as "disturbances in sexual desire and in the psychophysiological changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty". The female sexual response cycle consists of three phases: desire, arousal, and orgasm. Various organs of the external and internal genitalia, e.g. vagina, clitoris, labia minora, vestibular bulbs, pelvic floor muscles and uterus, contribute to female sexual function. During sexual arousal, genital blood flow and sensation are increased. The vaginal canal is moistened (lubrication). During orgasm, there is rhythmical contraction of the uterus and pelvic floor muscles. Within the central nervous system, hypothalamic, limbic-hippocampal structures play a central role for sexual arousal. Sexual arousal largely depends on the sympathetic nervous system. Moreover, nonadrenergic/noncholinergic neurotransmitters (NANC), e.g. vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), are involved in smooth muscle relaxation and enhancement of genital blood flow. Furthermore, various hormones may influence female sexual function. Estrogen has a significant role in maintaining vaginal mucosal epithelium as well as sensory thresholds and genital blood flow. Androgens primarily affect sexual desire, arousal, orgasm and the overall sense of well-being. The internationally accepted classification of female sexual dysfunction consists of hypoactive sexual desire disorders, sexual aversion disorders, sexual arousal disorders, orgasmic disorders and sexual pain disorders. Vascular insufficiency, e.g. due to atherosclerosis, and neurologic diseases, e.g. diabetic neuropathy, are major causes of sexual dysfunction. Additionally, sexual dysfunction may be due to changes in hormonal levels, medications with sexual side effects or of psychological origin. For the diagnosis of female sexual dysfunction, a detailed history should be taken initially, followed by a physical examination and laboratory studies. Physiologic monitoring of parameters of arousal potentially allows to diagnose organic diseases. Recordings at baseline and following sexual stimulation are recommended to determine pathologic changes that occur with arousal. Duplex Doppler sonography, photoplethysmography or the measurement of vaginal and minor labial oxygen tension may help to evaluate genital blood flow. Moreover, measurements of vaginal pH and compliance should be performed. Neurophysiological examination, e.g. measurement of the bulbocavernosus reflex and pudendal evoked potentials, genital sympathetic skin response (SSR), warm, cold and vibratory perception thresholds as well as testing of the pressure and touch sensitivity of the external genitalia, should be performed to evaluate neurogenic etiologies. Medical management of female sexual dysfunction so far is primarily based on hormone replacement therapy. Application of estrogen results in decreased pain and burning during intercourse. The efficacy of various other medications, e.g. sildenafil, L-arginine, yohimbine, phentolamine, apomorphine and prostaglandin E1, in the treatment of female sexual dysfunction is still under investigation.

Bioartificial organ support for hepatic, renal, and hematologic failure.

PubMed

Maguire, P J; Stevens, C; Humes, H D; Shander, A; Halpern, N A; Pastores, S M

2000-10-01

The current strategy to the treatment of SIRS and MODS uses a multidisciplinary approach that emphasizes supportive therapy. Herein, we have presented a futuristic approach that focuses on replacing the function of failed organs using bioartificial technology (Table 1). Bioartificial organ technology may allow the intensivist to provide physiologic organ replacement either as a bridge to transplantation or as a "time-buying" element until native organs that have become acutely dysfunctional or nonfunctional in a variety of clinical settings, can recover their function or regenerate their mass. As bioartificial organ technology matures, it is conceivable as an ultimate goal that non-immunogenic bioartificial organs would be miniaturized or redesigned and acutely placed within the intracorporeal space as replacement organs.

[Immunological Markers in Organ Transplantation].

PubMed

Beckmann, J H; Heits, N; Braun, F; Becker, T

2017-04-01

The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

PubMed

MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

2012-10-01

The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for efficacy and interaction during the concomitant evolution of acute and delayed key organ-specific subsyndromes.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

Sexual dysfunction, Part II: Diagnosis, management, and prognosis.

PubMed

Halvorsen, J G; Metz, M E

1992-01-01

Sexual problems are common but infrequently diagnosed. They are classified into four major categories: (1) sexual desire disorders, (2) sexual arousal disorders, (3) orgasmic disorders, and (4) sexual pain disorders. MEDLINE files from 1966 to the present were searched using the specific sexual dysfunctions as key words along with the general key word "sexual dysfunction" to review the published literature. Additional articles came from the reference lists of dysfunction-specific reviews. The key to diagnosis often rests on the physician's willingness to raise the issue with patients. A rational protocol can be followed to identify causative organic and psychogenic factors using the psychosexual and medical history, a comprehensive physical examination, psychological assessment instruments, laboratory tests, and special procedures. Current psychological treatment includes one or more of the following components: sensate focus exercises, cognitive-behavioral therapy, relaxation training, hypnosis and guided imagery, and group therapies. Specific techniques, such as directed self-stimulation, the stop-start and squeeze techniques, the sexological examination, systematic desensitization, and Kegel exercises, are added therapy when appropriate. Marital therapy to improve communication and resolve conflict is also part of standard therapy. Medical management can include pharmacologic agents to correct endocrine dysfunctions or to alter the progression of the sexual response. Surgical management can involve arterial revascularization, venous ligation, and penile implants. A noninvasive vacuum constriction device is also used to treat erectile disorders. The long-term prognosis of the sexual dysfunctions varies with the type of disorder and its causes. Generally good results (80 to 95 percent satisfaction) are obtained when treating vaginismus, dyspareunia, male erectile disorders, and female orgasmic dysfunctions. Long-term results are modestly successful (40 to 80 percent) when treating inhibited male orgasm and premature ejaculation. Long-term success is poorest at present for treating sexual desire disorders.

Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival.

PubMed

Newton, Chad A; Kozlitina, Julia; Lines, Jefferson R; Kaza, Vaidehi; Torres, Fernando; Garcia, Christine Kim

2017-08-01

Prior studies have shown that patients with pulmonary fibrosis with mutations in the telomerase genes have a high rate of certain complications after lung transplantation. However, few studies have investigated clinical outcomes based on leukocyte telomere length. We conducted an observational cohort study of all patients with pulmonary fibrosis who underwent lung transplantation at a single center between January 1, 2007, and December 31, 2014. Leukocyte telomere length was measured from a blood sample collected before lung transplantation, and subjects were stratified into 2 groups (telomere length <10th percentile vs ≥10th percentile). Primary outcome was post-lung transplant survival. Secondary outcomes included incidence of allograft dysfunction, non-pulmonary organ dysfunction, and infection. Approximately 32% of subjects had a telomere length <10th percentile. Telomere length <10th percentile was independently associated with worse survival (hazard ratio 10.9, 95% confidence interval 2.7-44.8, p = 0.001). Telomere length <10th percentile was also independently associated with a shorter time to onset of chronic lung allograft dysfunction (hazard ratio 6.3, 95% confidence interval 2.0-20.0, p = 0.002). Grade 3 primary graft dysfunction occurred more frequently in the <10th percentile group compared with the ≥10th percentile group (28% vs 7%; p = 0.034). There was no difference between the 2 groups in incidence of acute cellular rejection, cytopenias, infection, or renal dysfunction. Telomere length <10th percentile was associated with worse survival and shorter time to onset of chronic lung allograft dysfunction and thus represents a biomarker that may aid in risk stratification of patients with pulmonary fibrosis before lung transplantation. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress.

PubMed

Nagoor Meeran, M F; Jagadeesh, G S; Selvaraj, P

2016-01-25

Mitochondrial dysfunction has been suggested to be one of the important pathological events in isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist induced myocardial infarction (MI). In this context, we have evaluated the impact of thymol against ISO induced oxidative stress and calcium uniporter malfunction involved in the pathology of mitochondrial dysfunction in rats. Male albino Wistar rats were pre and co-treated with thymol (7.5 mg/kg body weight) daily for 7 days. Isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce MI. To explore the extent of cardiac mitochondrial damage, the activities/levels of cardiac marker enzymes, mitochondrial lipid peroxidation products, antioxidants, lipids, calcium, adenosine triphosphate and multi marker enzymes were evaluated. Isoproterenol induced myocardial infarcted rats showed a significant increase in the activities of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, lipids, calcium, and a significant decrease in the activities/levels of heart mitochondrial superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, isocitrate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase, and adenosine triphosphate. Thymol pre and co-treatment showed near normalized effects on all the biochemical parameters studied. Transmission electron microscopic findings and mitochondrial swelling studies confirmed our biochemical findings. The in vitro study also revealed the potent free-radical scavenging activity of thymol. Thus, thymol attenuates the involvement of ISO against oxidative stress and calcium uniporter malfunction associated with mitochondrial dysfunction in rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; Penninx, Brenda W J H; Dekker, Joost

2014-07-09

Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain. Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level). In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response. Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain.

Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders

PubMed Central

2014-01-01

Background Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain. Methods Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level). Results In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response. Conclusions Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain. PMID:25007969

[Motor system physiotherapy of the masticatory organ].

PubMed

Jagucka-Metel, Wioletta; Brzeska, Paulina; Sobolewska, Ewa; Machoy-Mokrzyńska, Anna; Baranowska, Agata

2013-01-01

The motor system of the masticatory organ is a complex morphological and functional structure. Its dysfunctions are manifested by various symptoms within the masticatory apparatus and in distant organs. The paper presents a discussion on the physiotherapeutic procedure for the treatment of disorders in the motor system of the masticatory organ. Therapeutic methods are presented, including: massage, trigger point therapy, kinesitherapy, biofeedback, manual therapy, postural re-education, kinesiotaping, physical interventions (TENS, hyaluronidase iontophoresis, ultrasound, laser therapy, and magnetoledotherapy). The paper points out the role of a comprehensive approach to the patient in order to eliminate the cause of disorders, going beyond symptomatic treatment.

Exertional heat stroke and acute liver failure: a late dysfunction

PubMed Central

Carvalho, Ana Sofia; Rodeia, Simão C; Silvestre, Joana; Póvoa, Pedro

2016-01-01

Heat stroke (HS) is defined as a severe elevation of core body temperature along with central nervous system dysfunction. Exertional heat stroke (EHS) with acute liver failure (ALF) is a rare condition. The authors report the case of a 25-year-old man with a history of cognitive enhancers’ intake who developed hyperthermia and neurological impairment while running an outdoor marathon. The patient was cooled and returned to normal body temperature after 6 h. He subsequently developed ALF and was transferred to the intensive care unit. Over-the-counter drug intake may have been related to heat intolerance and contributed to the event. The patient was successfully treated with conservative measures. In the presence of EHS, it is crucial to act promptly with aggressive total body cooling, in order to prevent progression of the clinical syndrome. Liver function must also be monitored, since it can be a late organ dysfunction. PMID:26969359

Post-operative cognitive dysfunction after knee arthroplasty: a diagnostic dilemma

PubMed Central

Yap, Kiryu K.; Joyner, Peter

2014-01-01

Post-operative cognitive dysfunction (POCD) is common in the elderly, and significantly impacts their recovery. We present an unusual diagnostic challenge where a 65-year-old male presented 4-week post-total knee arthroplasty with acute cognitive dysfunction lasting 19 days. Curiously, there were no findings uncovering a specific cause, but during investigation underlying predisposing factors such as depression, mild memory deficits and generalized brain volume loss were identified. The impression after psychogeriatric review was that of an organic brain syndrome with overlay of depression, with a complex presentation as POCD. After escalation of behavioural disturbance, he was commenced on anti-psychotic/depressant, with immediate response. We emphasize the importance of pre-operative evaluation of cognitive function and risk factors in all geriatric patients undergoing elective surgery, and the need for further characterization of POCD, as well as experimental research elucidating the underlying mechanisms to better identify and treat this important post-surgical phenomenon. PMID:25988029

Neurologic Complications of Transplantation.

PubMed

Dhar, Rajat

2018-02-01

Neurologic disturbances including encephalopathy, seizures, and focal deficits complicate the course 10-30% of patients undergoing organ or stem cell transplantation. While much or this morbidity is multifactorial and often associated with extra-cerebral dysfunction (e.g., graft dysfunction, metabolic derangements), immunosuppressive drugs also contribute significantly. This can either be through direct toxicity (e.g., posterior reversible encephalopathy syndrome from calcineurin inhibitors such as tacrolimus in the acute postoperative period) or by facilitating opportunistic infections in the months after transplantation. Other neurologic syndromes such as akinetic mutism and osmotic demyelination may also occur. While much of this neurologic dysfunction may be reversible if related to metabolic factors or drug toxicity (and the etiology is recognized and reversed), cases of multifocal cerebral infarction, hemorrhage, or infection may have poor outcomes. As transplant patients survive longer, delayed infections (such as progressive multifocal leukoencephalopathy) and post-transplant malignancies are increasingly reported.

Endothelial progenitor cells dysfunction and impaired tissue reparation: The missed link in diabetes mellitus development.

PubMed

Berezin, Alexander E

Diabetes mellitus (DM) is considered a leading cause of premature cardiovascular (CV) mortality and morbidity in general population and in individuals with known CV disease. Recent animal and clinical studies have shown that reduced number and weak function of endothelial progenitor cells (EPCs) may not only indicate to higher CV risk, but contribute to the impaired heart and vessels reparation in patients with DM. Moreover, EPCs having a protective impact on the vasculature may mediate the functioning of other organs and systems. Therefore, EPCs dysfunction is probably promising target for DM treatment strategy, while the role of restoring of EPCs number and functionality in CV risk diminish and reduce of DM-related complications is not fully clear. The aim of the review is summary of knowledge regarding EPCs dysfunction in DM patients. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Management of female infertility from hormonal causes.

PubMed

Luciano, Antony A; Lanzone, Antonio; Goverde, Angelique J

2013-12-01

Hormonal causes of female infertility involve ovulatory dysfunctions that may result from dysfunction of the hypothalamic-pituitary-ovarian axis, peripheral endocrine glands, nonendocrine organs, or metabolic disorders. It is important to think of anovulation not as a diagnosis but as a symptom of a metabolic or endocrine disorder that requires a thorough diagnostic evaluation to identify the specific cause and to implement effective therapies that assure the best possible pregnancy outcome and avoid long-term adverse health consequences. In most instances, the medical history points to the underlying dysfunction, which can usually be confirmed with laboratory or imaging tests. For more challenging cases, more extensive evaluations may be needed, including perturbation studies. Nevertheless, the management of anovulatory infertility is gratifying because its causes are often manifest and the treatment usually results in resumption of ovulatory cycles, restoration of fertility, and healthy offspring through natural conception without requiring expensive and intrusive assisted reproductive technologies. © 2013.

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

PubMed Central

Gao, Kun; Swarup, Vivek; Versano, Revital; Dong, Hongmei; Jordan, Maria C

2017-01-01

Friedreich's ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model of Fxn deficiency that enabled us to control the onset and progression of disease phenotypes by the modulation of Fxn levels. Systemic knockdown of Fxn in adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease. PMID:29257745

Mechanisms of Mitochondrial Dysfunction in Autism

DTIC Science & Technology

2011-07-01

findings contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position, policy or...ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES...8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING / MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S

Immunologic alterations and the pathogenesis of organ failure in the ICU.

PubMed

Opal, Steven M

2011-10-01

Rapid and marked alterations of innate and adaptive immunity typify the host response to systemic infection and acute inflammatory states. Immune dysfunction contributes to the development of organ failure in most patients with critical illness. The molecular mechanisms by which microbial pathogens and tissue injury activate myeloid cells and prime cellular and humoral immunity are increasingly understood. An early and effective immune response to microbial invasion is essential to mount an effective antimicrobial response. However, unchecked and nonresolving inflammation can induce diffuse vasodilation, increased capillary permeability, microvascular damage, coagulation activation, and organ dysfunction. Control of the inflammatory response to limit tissue damage, yet retain the antimicrobial responses in critically ill patients with severe infection, has been sought for decades. Anti-inflammatory approaches might be beneficial in some patients but detrimental in others. It is now clear that a state of sepsis-induced immune suppression can follow the immune activation phase of sepsis. In carefully selected patients, a better therapeutic strategy might be to provide immunoadjuvants to reconstitute immune function in intensive care unit (ICU) patients. Proresolving agents are also in development to terminate acute inflammatory reactions without immune suppression. This brief review summarizes the current understanding of the fundamental immune alterations in critical illness that lead to organ failure in critical illness. © Thieme Medical Publishers.

Mechanisms and assessment of IgG4-related disease: lessons for the rheumatologist.

PubMed

Yamamoto, Motohisa; Takahashi, Hiroki; Shinomura, Yasuhisa

2014-03-01

Recognition of IgG4-related disease as an independent chronic inflammatory disorder is a relatively new concept; previously, the condition was thought to represent a subtype of Sjögren's syndrome. IgG4-related disease is characterized by elevated serum levels of IgG4 and inflammation of various organs, with abundant infiltration of IgG4-bearing plasma cells, storiform fibrosis and obliterative phlebitis representing the major histopathological features of the swollen organs. The aetiology and pathogenesis of this disorder remain unclear, but inflammation and subsequent fibrosis occur due to excess production of type 2 T-helper-cell and regulatory T-cell cytokines. The disease can comprise various organ manifestations, such as dacryoadenitis and sialadenitis (also called Mikulicz disease), type 1 autoimmune pancreatitis, kidney dysfunction and lung disease. Early intervention using glucocorticoids can improve IgG4-related organ dysfunction; however, patients often relapse when doses of these agents are tapered. The disease has also been associated with an increased incidence of certain malignancies. Increased awareness of IgG4-related disease might lead to consultation with rheumatologists owing to its clinical, and potentially pathogenetic, similarities with certain rheumatic disorders. With this in mind, we describe the pathogenic mechanisms of IgG4-related disease, and outline considerations for diagnosis and treatment of the condition.

Biomorphic Multi-Agent Architecture for Persistent Computing

NASA Technical Reports Server (NTRS)

Lodding, Kenneth N.; Brewster, Paul

2009-01-01

A multi-agent software/hardware architecture, inspired by the multicellular nature of living organisms, has been proposed as the basis of design of a robust, reliable, persistent computing system. Just as a multicellular organism can adapt to changing environmental conditions and can survive despite the failure of individual cells, a multi-agent computing system, as envisioned, could adapt to changing hardware, software, and environmental conditions. In particular, the computing system could continue to function (perhaps at a reduced but still reasonable level of performance) if one or more component( s) of the system were to fail. One of the defining characteristics of a multicellular organism is unity of purpose. In biology, the purpose is survival of the organism. The purpose of the proposed multi-agent architecture is to provide a persistent computing environment in harsh conditions in which repair is difficult or impossible. A multi-agent, organism-like computing system would be a single entity built from agents or cells. Each agent or cell would be a discrete hardware processing unit that would include a data processor with local memory, an internal clock, and a suite of communication equipment capable of both local line-of-sight communications and global broadcast communications. Some cells, denoted specialist cells, could contain such additional hardware as sensors and emitters. Each cell would be independent in the sense that there would be no global clock, no global (shared) memory, no pre-assigned cell identifiers, no pre-defined network topology, and no centralized brain or control structure. Like each cell in a living organism, each agent or cell of the computing system would contain a full description of the system encoded as genes, but in this case, the genes would be components of a software genome.

Surface Modified Particles By Multi-Step Michael-Type Addition And Process For The Preparation Thereof

DOEpatents

Cook, Ronald Lee; Elliott, Brian John; Luebben, Silvia DeVito; Myers, Andrew William; Smith, Bryan Matthew

2005-05-03

A new class of surface modified particles and a multi-step Michael-type addition surface modification process for the preparation of the same is provided. The multi-step Michael-type addition surface modification process involves two or more reactions to compatibilize particles with various host systems and/or to provide the particles with particular chemical reactivities. The initial step comprises the attachment of a small organic compound to the surface of the inorganic particle. The subsequent steps attach additional compounds to the previously attached organic compounds through reactive organic linking groups. Specifically, these reactive groups are activated carbon—carbon pi bonds and carbon and non-carbon nucleophiles that react via Michael or Michael-type additions.

Prescription opioids for back pain and use of medications for erectile dysfunction.

PubMed

Deyo, Richard A; Smith, David H M; Johnson, Eric S; Tillotson, Carrie J; Donovan, Marilee; Yang, Xiuhai; Petrik, Amanda; Morasco, Benjamin J; Dobscha, Steven K

2013-05-15

Cross-sectional analysis of electronic medical and pharmacy records. To examine associations between use of medication for erectile dysfunction or testosterone replacement and use of opioid therapy, patient age, depression, and smoking status. Males with chronic pain may experience erectile dysfunction related to depression, smoking, age, or opioid-related hypogonadism. The prevalence of this problem in back pain populations and the relative importance of several risk factors are unknown. We examined electronic pharmacy and medical records for males with back pain in a large group model health maintenance organization during 2004. Relevant prescriptions were considered for 6 months before and after the index visit. There were 11,327 males with a diagnosis of back pain. Males who received medications for erectile dysfunction or testosterone replacement (n = 909) were significantly older than those who did not and had greater comorbidity, depression, smoking, and use of sedative-hypnotics. In logistic regressions, the long-term use of opioids was associated with greater use of medications for erectile dysfunction or testosterone replacement compared with no opioid use (odds ratio, 1.45; 95% confidence interval, 1.12-1.87, P < 0.01). Age, comorbidity, depression, and use of sedative-hypnotics were also independently associated with the use of medications for erectile dysfunction or testosterone replacement. Patients prescribed daily opioid doses of 120 mg of morphine-equivalents or more had greater use of medication for erectile dysfunction or testosterone replacement than patients without opioid use (odds ratio, 1.58; 95% confidence interval, 1.03-2.43), even with adjustment for the duration of opioid therapy. Dose and duration of opioid use, as well as age, comorbidity, depression, and use of sedative-hypnotics, were associated with evidence of erectile dysfunction. These findings may be important in the process of decision making for the long-term use of opioids. 4.

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

PubMed

da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

2018-04-24

In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in most RCTs. The RIFLE, AKIN and KDIGO classification systems were infrequently used; renal dysfunction was generally defined using the SOFA score.

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.

PubMed

Hinder, Lucy M; Park, Meeyoung; Rumora, Amy E; Hur, Junguk; Eichinger, Felix; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

2017-09-01

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Donor information based prediction of early allograft dysfunction and outcome in liver transplantation.

PubMed

Hoyer, Dieter P; Paul, Andreas; Gallinat, Anja; Molmenti, Ernesto P; Reinhardt, Renate; Minor, Thomas; Saner, Fuat H; Canbay, Ali; Treckmann, Jürgen W; Sotiropoulos, Georgios C; Mathé, Zoltan

2015-01-01

Poor initial graft function was recently newly defined as early allograft dysfunction (EAD) [Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010; 16: 943]. Aim of this analysis was to evaluate predictive donor information for development of EAD. Six hundred and seventy-eight consecutive adult patients (mean age 51.6 years; 60.3% men) who received a primary liver transplantation (LT) (09/2003-12/2011) were included. Standard donor data were correlated with EAD and outcome by univariable/multivariable logistic regression and Cox proportional hazards to identify prognostic donor factors after adjustment for recipient confounders. Estimates of relevant factors were utilized for construction of a new continuous risk index to develop EAD. 38.7% patients developed EAD. 30-day survival of grafts with and without EAD was 59.8% and 89.7% (P < 0.0001). 30-day survival of patients with and without EAD was 68.5% and 93.1% (P < 0.0001) respectively. Donor body mass index (P = 0.0112), gGT (P = 0.0471), macrosteatosis (P = 0.0006) and cold ischaemia time (CIT) (P = 0.0031) were predictors of EAD. Internal cross validation showed a high predictive value (c-index = 0.622). Early allograft dysfunction correlates with early results of LT and can be predicted by donor data only. The newly introduced risk index potentially optimizes individual decisions to accept/decline high risk organs. Outcome of these organs might be improved by shortening CIT. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... Effectiveness of a Proposed Rule Change To Amend Its Rule Related to Multi-Class Broad- Based Index Option... Rule Change The Exchange proposes to amend its rule related to multi-class broad-based index option... is to (i) clarify that the term ``Multi-Class Broad-Based Index Option Spread Order (Multi-Class...

Oestrogen-deficiency inducing haematopoiesis dysfunction via reduction in haematopoietic stem cells and haematopoietic growth factors in rats

PubMed Central

Qiu, Xi; Yuan, Xiang-Gui; Jin, Xiao-li; He, Xin; Zhu, Lei; Zhao, Xiao-Ying

2012-01-01

Summary Haematopoiesis is a self-renewing and multi-directional differentiation process of haematopoietic stem cells (HSCs), which is modulated very precisely by the haematopoietic microenvironment in bone marrow. Our previous study has demonstrated that oestrogen-deficiency leads to haematopoiesis dysfunction which manifests as a decrease in haematopoietic tissues and an increase in adipose tissues in bone marrow. However, the mechanism involved in the oestrogen-deficiency effects on haematopoiesis dysfunction is not completely understood. In this study, we established an oestrogen-deficiency rat model by ovariectomy (OVX group). Haematopoiesis was evaluated at the 12th, 16th, 20th, 24th and 28th weeks after operation in the OVX group and its control (Sham group) by pathological examination; the number and function of HSCs were evaluated by flow cytometry analysis and colony-forming assay respectively. Haematopoietic growth factors levels including granulocyte/macrophage-colony-stimulating factor (GM-CSF), stem cell factor (SCF) and interleukin-3 (IL-3) were examined by ELISA kits at different time points. We found that in the OVX group, haematopoiesis dysfunction in bone marrow was observed (P < 0.05) from the 12th week when compared with the Sham group, and extramedullary haematopoiesis began to appear in the liver and spleen from the 16th week. The number of HSCs and colony-forming units-granulocyte/macrophage (CFUs-GM) in bone marrow was reduced significantly (P < 0.05) from the 20th and 16th week respectively. Furthermore, GM-CSF, SCF and IL-3 in the OVX group decreased significantly (P < 0.05) since the 12th, 16th and 24th week respectively. Taken together, these results suggested that oestrogen is required for normal haematopoiesis. Oestrogen-deficiency inducing haematopoiesis dysfunction may be via reduction in HSCs and haematopoietic growth factors at a late stage. PMID:22583131

Oestrogen-deficiency inducing haematopoiesis dysfunction via reduction in haematopoietic stem cells and haematopoietic growth factors in rats.

PubMed

Qiu, Xi; Yuan, Xiang-Gui; Jin, Xiao-Li; He, Xin; Zhu, Lei; Zhao, Xiao-Ying

2012-06-01

Haematopoiesis is a self-renewing and multi-directional differentiation process of haematopoietic stem cells (HSCs), which is modulated very precisely by the haematopoietic microenvironment in bone marrow. Our previous study has demonstrated that oestrogen-deficiency leads to haematopoiesis dysfunction which manifests as a decrease in haematopoietic tissues and an increase in adipose tissues in bone marrow. However, the mechanism involved in the oestrogen-deficiency effects on haematopoiesis dysfunction is not completely understood. In this study, we established an oestrogen-deficiency rat model by ovariectomy (OVX group). Haematopoiesis was evaluated at the 12th, 16th, 20th, 24th and 28th weeks after operation in the OVX group and its control (Sham group) by pathological examination; the number and function of HSCs were evaluated by flow cytometry analysis and colony-forming assay respectively. Haematopoietic growth factors levels including granulocyte/macrophage-colony-stimulating factor (GM-CSF), stem cell factor (SCF) and interleukin-3 (IL-3) were examined by ELISA kits at different time points. We found that in the OVX group, haematopoiesis dysfunction in bone marrow was observed (P < 0.05) from the 12th week when compared with the Sham group, and extramedullary haematopoiesis began to appear in the liver and spleen from the 16th week. The number of HSCs and colony-forming units-granulocyte/macrophage (CFUs-GM) in bone marrow was reduced significantly (P < 0.05) from the 20th and 16th week respectively. Furthermore, GM-CSF, SCF and IL-3 in the OVX group decreased significantly (P < 0.05) since the 12th, 16th and 24th week respectively. Taken together, these results suggested that oestrogen is required for normal haematopoiesis. Oestrogen-deficiency inducing haematopoiesis dysfunction may be via reduction in HSCs and haematopoietic growth factors at a late stage. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Psychosocial consequences of head injury in children and adolescents: implications for rehabilitation.

PubMed

Livingston, M G; McCabe, R J

1990-01-01

Studies measuring psychosocial outcome in children and adolescents have shown that head injury leads to cognitive impairment which is directly related to the severity of injury in those with very severe head injury. Psychiatric disorders are also related to the severity of injury but here the relationship suggests that mediating factors are involved. No specific pattern of post-traumatic psychological/psychiatric dysfunction emerges from the studies, but it is clear that, as with adults, psychosocial recovery lags behind physical. Head injury affects the functioning of the young person in the family, at school, and within the wider community, often resulting in a secondary handicap of low self-esteem. The multitude of deficits which are a consequence of severe head injury present a challenge for rehabilitation specialists. A multi-disciplinary, multi-specialist, and multi-agency response is required. As a result, families are often presented with a bewildering array of treatments and programmes at different agencies. A case manager can be helpful in ensuring the appropriate use of available resources and can be the one professional in charge of a coordinating case record.

National Cancer Institute-National Heart, Lung and Blood Institute/pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: long-term organ damage and dysfunction.

PubMed

Nieder, Michael L; McDonald, George B; Kida, Aiko; Hingorani, Sangeeta; Armenian, Saro H; Cooke, Kenneth R; Pulsipher, Michael A; Baker, K Scott

2011-11-01

Long-term complications after hematopoietic cell transplantation (HCT) have been studied in detail. Although virtually every organ system can be adversely affected after HCT, the underlying pathophysiology of these late effects remain incompletely understood. This article describes our current understanding of the pathophysiology of late effects involving the gastrointestinal, renal, cardiac, and pulmonary systems, and discusses post-HCT metabolic syndrome studies. Underlying diseases, pretransplantation exposures, transplantation conditioning regimens, graft-versus-host disease, and other treatments contribute to these problems. Because organ systems are interdependent, long-term complications with similar pathophysiologic mechanisms often involve multiple organ systems. Current data suggest that post-HCT organ complications result from cellular damage that leads to a cascade of complex events. The interplay between inflammatory processes and dysregulated cellular repair likely contributes to end-organ fibrosis and dysfunction. Although many long-term problems cannot be prevented, appropriate monitoring can enable detection and organ-preserving medical management at earlier stages. Current management strategies are aimed at minimizing symptoms and optimizing function. There remain significant gaps in our knowledge of the pathophysiology of therapy-related organ toxicities disease after HCT. These gaps can be addressed by closely examining disease biology and identifying those patients at greatest risk for adverse outcomes. In addition, strategies are needed for targeted disease prevention and health promotion efforts for individuals deemed at high risk because of their genetic makeup or specific exposure profile. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Urgent Chemotherapy in Sepsis-Like Shock Related to Hematologic Malignancies.

PubMed

Cherruault, Marlène; Le Goff, Marielle; Tamburini, Jérôme; Pène, Frédéric

2018-05-01

Hematologic malignancies may result in multiple organ involvement including pulmonary and renal dysfunctions, and the less common acute circulatory failure. We herein addressed the outcome of patients with sepsis-like shock related to aggressive hematologic malignancies. A 10-year (2007-2016) monocenter retrospective study. A medical ICU in a tertiary care center. Patients with circulatory shock requiring vasopressors and who subsequently received chemotherapy. Shock was presumably related to the underlying malignancy after ruling out an ongoing or new-onset infectious process. The extent and time course of organ failures was assessed by a modified Sequential Organ Failure Assessment score devoid of the platelet component. None. Seventeen patients were included, including 13 with non-Hodgkin lymphoma, two with hyperleukocytic acute myeloid leukemia, and two with "Human Herpes virus 8"-associated multicentric Castleman's disease. The following associated conditions prompted urgent administration of chemotherapy: tumor lysis syndrome (n = 10), hemophagocytic lymphohistiocytosis (n = 3), compressive bulky tumor (n = 3), pulmonary involvement (n = 3), and disseminated intravascular coagulation (n = 1). Following the initiation of chemotherapy, a number of patients died rapidly from untractable multiple organ failure. In contrast, chemotherapy led to a fast and dramatic improvement in organ failures in early survivors, as shown by the decrease in the modified Sequential Organ Failure Assessment score. However, the overall outcome was poor since only four and three patients could be discharged alive from the ICU and the hospital, and three and two patients remained alive at 6 months and 1 year. Multiple organ dysfunction syndrome related to hematologic malignancies is associated with a dismal outcome. A chemotherapy trial may provide a fast prognostic assessment of the reversibility of organ failure.

Molecular mechanisms of inner ear development.

PubMed

Wu, Doris K; Kelley, Matthew W

2012-08-01

The inner ear is a structurally complex vertebrate organ built to encode sound, motion, and orientation in space. Given its complexity, it is not surprising that inner ear dysfunction is a relatively common consequence of human genetic mutation. Studies in model organisms suggest that many genes currently known to be associated with human hearing impairment are active during embryogenesis. Hence, the study of inner ear development provides a rich context for understanding the functions of genes implicated in hearing loss. This chapter focuses on molecular mechanisms of inner ear development derived from studies of model organisms.

Organ failure avoidance and mitigation strategies in surgery.

PubMed

McConnell, Kevin W; Coopersmith, Craig M

2012-04-01

Postoperative organ failure is a challenging disease process that is better prevented than treated. Providers should use close observation and clinical judgment, and checklists of best practices to minimize the risk of organ failure in their patients. The treatment of multiorgan dysfunction syndrome (MODS) generally remains supportive, outside of rapid initiation of source control (when appropriate) and targeted antibiotic therapy. More specific treatments may be developed as the complex pathophysiology of MODS is better understood and more homogenous patient populations are selected for study. Copyright © 2012 Elsevier Inc. All rights reserved.

What is regressive autism and why does it occur? Is it the consequence of multi-systemic dysfunction affecting the elimination of heavy metals and the ability to regulate neural temperature?

PubMed Central

Ewing, Graham E.

2009-01-01

There is a compelling argument that the occurrence of regressive autism is attributable to genetic and chromosomal abnormalities, arising from the overuse of vaccines, which subsequently affects the stability and function of the autonomic nervous system and physiological systems. That sense perception is linked to the autonomic nervous system and the function of the physiological systems enables us to examine the significance of autistic symptoms from a systemic perspective. Failure of the excretory system influences elimination of heavy metals and facilitates their accumulation and subsequent manifestation as neurotoxins: the long-term consequences of which would lead to neurodegeneration, cognitive and developmental problems. It may also influence regulation of neural hyperthermia. This article explores the issues and concludes that sensory dysfunction and systemic failure, manifested as autism, is the inevitable consequence arising from subtle DNA alteration and consequently from the overuse of vaccines. PMID:22666668

Preliminary evaluation of a self-directed video-based 1-2-3 Magic parenting program: a randomized controlled trial.

PubMed

Porzig-Drummond, Renata; Stevenson, Richard J; Stevenson, Caroline

2015-03-01

The current study examined the effectiveness of a self-directed video-based format of the 1-2-3 Magic parenting program in reducing dysfunctional parenting and child problem behaviors. Eighty-four parents of children aged 2-10 were randomly assigned to either the intervention group (n = 43) or the waitlist control group (n = 41). Participants in the intervention group reported significantly less problem behaviors for their children, and significantly less dysfunctional parenting, at post-intervention when compared to the control group. The results were maintained at 6-month follow-up. There was no significant change on measures of parental adjustment for either group. The current results provide preliminary support for the conclusion that the video-based self-directed format of the 1-2-3 Magic parenting program is suitable as an entry-level intervention in a multi-level intervention model and is suitable for inclusion in a population approach to parenting program delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning.

PubMed

Kumar, Vijay; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

2016-10-04

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle weakness, paralysis and finally death. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and proteasomal dysfunction. Although numerous pathological mechanisms have been explained, ALS remains incurable disease because of failure of clinical trials and lack of any effective therapy. The rapid advancement in genetic discoveries in ALS emphasizes the point that ALS is a multi-subtype syndrome rather than a single disease. This can be argued as one of the single reason why many previous therapeutic drug trials have failed. Efforts to develop novel ALS treatments which target specific pathomechanisms are currently being pursued. Herein, we review the recent discovery and preclinical characterization of neuroprotective compounds and compare their effects on disease onset, duration and survival. Furthermore, the structure-activity relationships of these agents are analyzed with the overall goal of developing a screening strategy for future clinical applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Long lasting effects of chronic heavy cannabis abuse.

PubMed

Nestoros, Joannis N; Vakonaki, Elena; Tzatzarakis, Manolis N; Alegakis, Athanasios; Skondras, Markos D; Tsatsakis, Aristidis M

2017-06-01

The purpose of this study was to evaluate the extent of short-term memory impairment and schizophrenia-like symptoms in heavy and systematic cannabis users and the association between the severity of abuse and the longevity of its persistent symptoms after refraining from such use. A complete psychiatric examination and a psychometric evaluation were performed in 48 solely cannabis users. Additionally, head hair samples were analyzed and the detected cannabinoids levels were correlated with the psychometric findings. A total of 33.3% (n = 16) of the total examined cannabis users were currently imprisoned. The years of abuse ranged from 1 to 35 years and the median daily dose was 5.84.4 gr and 4.84.0 gr for prisoners (n = 16) and non prisoners (n = 32), respectively. A total of 39.6% of the users experienced hallucinations (mostly auditory), 54.2% experienced delusions (mostly ideas of reference and persecution), 85.4% had organic brain dysfunction in a test addressing visual-motor functioning and visual perception skills, and all users (100%) were found to have organic brain dysfunction in a test of visual memory immediate recall. The cannabinoid metabolite levels in the hair samples were consistent with the reported history of substance abuse and total grams of consumption for the participants below 35 years old (p < .001). Statistically elevated cannabinoids levels were observed in users with auditory hallucinations compared to users without any hallucinations (p = .019). The existence of hallucinations, delusions, and organic brain dysfunction in heavy cannabis users seems to be associated with cannabinoid levels in hair. The continuation of persistent symptoms 3 months after the discontinuation of cannabis abuse, was a remarkable finding. We provide evidence that chronic and heavy cannabis abuse results in long-lasting brain dysfunction in all users and in long-lasting schizophrenia-like psychotic symptoms in more than half of all users. These findings suggest a reevaluation of the current classification of cannabis as a "soft narcotic" which erroneously, therefore, is typically considered harmless. (Am J Addict 2017;26:335-342). © 2017 American Academy of Addiction Psychiatry.