bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of lupus skin involvement with quinacrine and hydroxychloroquine
Authors: Cavazzana I , Sala R , Bazzani C , Ceribelli A , Zane C , Cattaneo R , Tincani A , Calzavara-Pinton PG , Franceschini F
Published: June 2009

To evaluate the efficacy of hydroxychloroquine (HCQ) and quinacrine (Qn) association, at two different dosages, in treatment of lupus skin lesions not responding to HCQ alone. Thirty-four patients, affected by cutaneous and systemic lupus erythematosus, were retrospectively analysed. They were treated by HCQ (5 mg/Kg/qd) and Qn with two regimens: 100 mg/qd (29 cases) and 50 mg/qd (5 cases). Discoid lupus erythematosus (19 cases), acute malar rash (6 cases), chilblain lupus (4 cases) showed a significant improvement with combination therapy ( P = 0.009, P = 0.019, and P = 0.04, respectively). Ten patients with subacute cutaneous lupus showed a partial response, whereas lupus profundus didn’t improve. The same overall response rate was recorded comparing two Qn regimens, but subjects taking 100 mg/qd improved more rapidly than the others ( P = 0.001). Ten patients developed side effects, mainly represented by skin yellowish discolouration. Depression and severe headache with nausea, which were globally recorded in two cases, led to drug withdrawal. One additional case of hepatitis was recorded in a patient with preexisting Hepatitis C virus (HCV) infection. Combination of HCQ and Qn is rapidly effective at 100 mg/qd and well tolerated in the treatment of lupus skin lesions unresponsive to HCQ alone.
Efficacy and safety of infliximab in active SLE: a pilot study
Authors: Uppal SS , Hayat SJ , Raghupathy R
Published: June 2009

Tumour necrosis factor-α (TNF-α) plays a major role in propagating the inflammatory processes responsible for tissue damage in systemic lupus erythematosus (SLE) and is overexpressed both systemically and locally in this disease. Hence, this pilot study was carried out to assess the safety and efficacy of TNF blockade in patients with active SLE. A total of 46 individuals (27 patients with active SLE and 19 healthy control volunteers) were the subjects of this study. Nine patients with SLE were allocated to treatment arm and 18 were allocated to control arm. In addition to conventional treatment, treatment arm received infliximab infusions 3 mg/kg body weight at 0, 2, 6 weeks and then q 8 weeks for a total of 24 weeks, that is, a total of five doses. Patients were closely monitored for infection. Clinical, laboratory and treatment data were entered into a pre-designed proforma. Health status (SF-36), patient global assessment (PGA) of disease activity, disease activity scores by SLEDAI and organ damage by SLICC/ACR-DI (American College Rheumatology) were measured at baseline and end of the study. Relevant immunological studies included serum levels of TNF-α and soluble TNF receptors-1 (p55 srTNF-α) and -2 (p75 srTNF-α), C3 and C4 complement levels, anti-dsDNA antibody titres (IgM, IgG and IgA isotypes), anti-cardiolipin titres (IgM, IgG and IgA isotypes) and anti-β2GPI (Glycoprotein I) antibody titres (IgM, IgG and IgA isotypes). Four patients from treatment arm dropped out due to infliximab infusion reaction and 12 patients dropped out from the control arm. The treatment group showed significantly greater improvement in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Improvements in several SF-36 subscales, PGA and VAS-Fatigue (Visual Analogue Scale) were also greater in the treatment group but did not achieve statistical significance. The mean levels of TNF-α, soluble TNF receptors-1 (p55 srTNF-α) and -2 (p75 srTNF-α) were higher in the SLE group compared with the healthy controls but did not change significantly over the study period. We did not face any safety issues with infliximab in this study. In view of improvement in several SLE parameters and good safety profile of infliximab, anti-TNF-α therapy is an interesting candidate approach for treating SLE.
The detecting and clinical value of anti-cyclic citrullinated peptide antibodies in patients with systemic lupus erythematosus
Authors: Qing Y-F , Zhang Q-B , Zhou J-G , Yuan G-H , Wei J , Xing Y , Liu J-P , Jiang L , Chen J-P
Published: June 2009

The aim of this article is to compare the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in systemic lupus erythematosus (SLE) patients with and without arthritis and in patients with rheumatoid arthritis (RA). Anti-CCP antibodies were measured using ELISA in 159 SLE patients with arthritis (12 patients with erosive arthritis), 108 SLE patients without arthritis, 76 RA patients, and 87 healthy subjects (controls). The following had anti-CCP antibodies above the cut-off level (5 U/ml): 27.3% of SLE patients, 42.1% SLE patients with arthritis, 5.6% SLE patients without arthritis, 85.5% RA patients and 1.1% controls. The mean titre of anti-CCP antibodies in the SLE group was much lower than that in the RA group (33 ± 72 vs. 160 ± 125 U/ml), but higher in SLE patients with erosive arthritis than those with non-erosive arthritis (221 ± 88 vs. 32 ± 42 U/ml). Hand poly-arthritis occurred more frequently in anti-CCP-positive SLE patients with erosive arthritis than those with non-erosive arthritis. Anti-CCP antibodies were prevalent in some SLE patients, more prevalent in SLE patients with arthritis than those without arthritis. Anti-CCP-positive SLE patients were more likely associated with hand poly-arthritis, and high titre of anti-CCP antibodies might be used as a predictor for the complication of erosive arthritis.
Are endothelial microparticles potential markers of vascular dysfunction in the antiphospholipid syndrome?
Authors: Pericleous C , Giles I , Rahman A
Published: June 2009

Vascular dysfunction is key to the development of thrombosis in the antiphospholipid syndrome. This has been largely demonstrated by the upregulation of various cell surface and intracellular signalling molecules, as well as proinflammatory cytokine release from activated endothelial cells. Endothelial microparticles (EMP) are a further marker of endothelial activation but have been less extensively studied. We summarise evidence suggesting that these microparticles may be critical effectors of thrombosis in the antiphospholipid syndrome. There is evidence that levels of EMP are raised in patients with circulating antiphospholipid antibodies and that these EMP may be prothrombotic. The balance between markers of endothelial dysfunction (including EMP and circulating endothelial cells) and markers of repair such as circulating endothelial progenitor cells may be abnormal in patients with APS but this has not been proved and requires further study.
Angiogenic activity in sera of patients with systemic lupus erythematosus
Authors: Sakly N , Mirshahi P , Ducros E , Soria J , Ghedira I , Mirshahi M
Published: June 2009

Angiogenesis plays a critical role in the pathogenesis of several connective tissue diseases. There is, however, relatively little information available on the role of angiogenesis in systemic lupus erythematosus (SLE). The aim of this study was to investigate the angiogenic activity in sera of patients with SLE and to determine the association between angiogenic activity and clinical complications. Sera from 66 Tunisian females with SLE and from 32 healthy blood donors were studied for their angiogenic activity using the in-vitro tube formation test on Matrigel. Samples were divided into five groups according to their angiogenic activity, which was scored from 0 (no angiogenesis) to 4 (high angiogenic activity). Samples from each group were then tested randomly to assess serum concentration of vascular endothelial growth factor (VEGF). No correlation was found between angiogenic activity scores and serum VEGF levels. Considering angiogenesis assessment in-vitro, sera of patients with SLE showed a much higher angiogenic activity than healthy controls since a high angiogenic score (score 4) is present in 43.9% of patients and in 6.3% of controls ( P < 0.0002). This high angiogenic activity is not correlated with disease activity; however, SLE patients with anti-dsDNA antibodies and those with nephritis showed higher angiogenic activity compared with patients without these complications since score 4 is found in 50.9% and 67.9% versus 9.1% ( P = 0.017) and 26.3% ( P < 0.001), respectively. In conclusion, our study showed that high serum angiogenic activity in SLE was not correlated with the VEGF levels. We suggest the use of the ‘in-vitro’ tube formation test as a better tool to study the angiogenic potential of sera. We found that in patients with SLE, serum angiogenic activity is increased compared with healthy controls. This high angiogenic activity is associated with renal complications and with the presence of anti-dsDNA antibodies. These findings suggest an involvement of angiogenesis disturbance in the pathogenesis of SLE.
Factors Affecting Vocational Rehabilitation Intervention Outcomes
Authors: Mwachofi Ari K. , Broyles Robert , Khaliq Amir
Published: June 2009

Vocational rehabilitation (VR) services are designed to help individuals with disabilities achieve gainful employment. This study examines VR’s effectiveness in assisting minorities achieve gainful employment. The study uses case management data from 617,149 cases closed by VR in 2006 in all states. It examines differences in access, employment, and earnings for White and ethnic minority clients. Multivariate techniques are used to assess factors that influence competitive employment outcomes, hourly earnings, and hours worked. Findings show significant differences in employment and earnings outcomes for minority and majority clients, with minorities faring worse. VR intervention length and per capita expenditures for services significantly influence employment and earnings outcomes. VR is more effective with White than with minority clients. There is a need to implement policies or practices that ensure equity in access to services that might translate into more equitable employment and earnings outcomes.
History and Expansion of Section 504 Student Eligibility: Implications for School Nurses
Authors: Zirkel Perry A.
Published: June 2009

This article presents an explanation of the eligibility criteria for K-12 students under Section 504 and its sister statute, the Americans with Disabilities Act (ADA). The explanation shows the evolving application of Section 504 to students in terms of three phases: awareness, constriction, and expansion. The latest phase, expansion, started with the January 1, 2009, effective date of the ADA Amendments (ADAA), which dramatically reversed the previous phase of judicial constriction of the eligibility criteria. The changes affect two of the three criteria in the definition of disability under Section 504 and the ADA: (a) an expanded list of illustrations of “major life activities” and (b) much less restrictive standards for interpreting “substantially limits.” As a result, the school nurse plays a more critical role as a member of or consultant to the school teams that determine student eligibility for and the contents appropriate in 504 Plans.
Vitamin E Does Not Regress Hypercholesterolemic Atherosclerosis
Authors: Prasad Kailash
Published: June 2009

Background: Suppression of hypercholesterolemic atherosclerosis with vitamin E is associated with reductions in oxidative stress without reductions in serum lipids. The objectives of this study were to determine if (1) vitamin E regresses hypercholesterolemic atherosclerosis; and (2) regression is associated with reductions in serum lipids and aortic oxidative stress. Methods and Results: The studies were conducted in 4 groups of rabbits: group I, control, regular diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (2 months) followed by regular diet (2 months); and group IV, 0.25% cholesterol diet (2 months) followed by regular diet with vitamin E (40 mg/kg body weight/day) (2 months). Blood samples were collected monthly for the measurement of serum lipids and oxidative stress (chemiluminescent activity of white blood cells [WBC-CL]). Aortas were removed at the end of the protocol for assessment of atherosclerotic lesions, and oxidative stress (malondialdehyde [MDA] and CL). Increases in serum lipids in group II were associated with an increase in oxidative stress and development of atherosclerosis. Serum lipids decreased to a similar extent in groups III and IV but the atherosclerotic lesions increased by 63% and 141% compared to group II. Acceleration of atherosclerosis in the rabbits on regular diet with or without vitamin E was associated with practically no change in the oxidative stress. Conclusion: These results suggest that (1) regular diet following a high-cholesterol diet decreased oxidative stress but did not induce regression of atherosclerosis; (2) vitamin E did not produce regression; and (3) regular diet with vitamin E following a high-cholesterol diet was not associated with an increase in oxidative stress but produced acceleration of atherosclerosis.
Perindopril decreases P wave dispersion in patients with stage 1 hypertension
Authors: Ozben Beste , Sumerkan Mutlu , Tanrikulu Azra Meryem , Papila-Topal Nurdan , Fak Ali Serdar , Toprak Ahmet
Published: June 2009

Introduction. Angiotensin-converting enzyme inhibitors prevent atrial fibrillation episodes by effective control of blood pressure and improving electrical and structural remodelling in the atria. Increased P wave dispersion (PWD) is a non-invasive electrocardiographic marker for paroxysmal atrial fibrillation. The aim of the study was to evaluate the effect of perindopril treatment on PWD in hypertensive patients. Methods. Forty-eight hypertensive patients (mean age 57.4±11.8 years, 18 men) were included. Blood pressure values were determined and 12-lead electrocardiograms were recorded at the beginning and at the first week, first month, third month and sixth month of the perindopril treatment.The difference between maximum and minimum P wave durations was calculated as PWD.

Results. PWDs were significantly shortened at the first, third and sixth months (41.7±8.8 ms, 39.1±6.9 ms and 38.3±7.1 ms, respectively) compared with baseline and first-week measurements (54.3±9.2 ms and 49.0±9.1 ms, respectively, p<0.001). Baseline PWD was correlated with body mass index (r=0.32, p=0.026), while PWD at the sixth month of treatment was significantly correlated with left atrial volume index (r=0.30, p=0.042). Multiple linear regression analysis revealed that PWD at the sixth month was related to baseline PWD (p=0.001).

Conclusion. Perindopril treatment significantly reduced PWD in hypertensive patients.
Effects of enalapril or nifedipine on muscle strength or functional capacity in elderly subjects. A double blind trial
Authors: Bunout Daniel , Barrera Gladys , de la Maza María Pía , Leiva Laura , Backhouse Claudia , Hirsch Sandra
Published: June 2009

Introduction. The inhibition of angiotensin-converting enzyme could be useful to avoid sarcopenia in the elderly.

Materials and methods. We compared in a prospective double blind trial, the effects of treatment with enalapril or nifedipine on muscle performance in hypertensive elderly subjects. Patients were followed for nine months, and at baseline, 4.5 months and the end of follow-up, quadriceps and hand grip muscle strength, walking capacity, timed up and go and the short physical performance test were measured. Results. During follow-up, more subjects on nifedipine than on enalapril discontinued the medication due to side-effects. No differences in the evolution of muscle strength, walking capacity or functional measures were observed. At nine months, plasma angiotensin-converting enzyme activity decreased by 6.0±2.5 U/L among patients on enalapril and increased by 8.5±4.2 U/L (p<0.001) among patients on nifedipine.

Conclusion. In this group of elderly subjects, enalapril was not superior to nifedipine with regard to the age-related decline of muscle performance.
Communicating Cancer Risk Reduction
Authors: Terre Lisa
Published: June 2009

This review discusses considerations in the development and dissemination of cancer risk reduction appeals and associated challenges to the amelioration of health-compromising behaviors. Strategic implications for empirically driven public policy initiatives and primary care also are addressed.
Imaging Features of Thyroid Involvement by Langerhans Cell Histiocytosis
Authors: Junewick Joseph J. , Braunreiter Chi , Fulton Barbara , Olsen Andrew
Published: June 2009

A 2-year-old male presented with fever, rash, right upper quadrant pain, and hyperbilirubinemia and was diagnosed with Langerhans cell histiocytosis (LCH). Periportal, hepatic, pulmonary, thymic, and thyroid involvement was noted on initial imaging. Thyroid gland involvement by LCH is rare. This case illustrates computed tomography, ultrasonography, and magnetic resonance imaging features of LCH of the thyroid.
Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome
Authors: Nawtaisong Pruksa , Keith James , Fraser Tresa , Balaraman Velmurugan , Kolokoltsov Andrey , Davey Robert A , Higgs Stephen , Mohammed Ahmed , Rongsriyam Yupha , Komalamisra Narumon , Fraser Malcolm J
Published: June 2009

Outbreaks of Dengue impose a heavy economic burden on developing countries in terms of vector control and human morbidity. Effective vaccines against all four serotypes of Dengue are in development, but population replacement with transgenic vectors unable to transmit the virus might ultimately prove to be an effective approach to disease suppression, or even eradication. A key element of the refractory transgenic vector approach is the development of transgenes that effectively prohibit viral transmission. In this report we test the effectiveness of several hammerhead ribozymes for suppressing DENV in lentivirus-transduced mosquito cells in an attempt to mimic the transgenic use of these effector molecules in mosquitoes. A lentivirus vector that expresses these ribozymes as a fusion RNA molecule using an Ae. aegypti tRNAval promoter and terminating with a 60A tail insures optimal expression, localization, and activity of the hammerhead ribozyme against the DENV genome. Among the 14 hammerhead ribozymes we designed to attack the DENV-2 NGC genome, several appear to be relatively effective in reducing virus production from transduced cells by as much as 2 logs. Among the sequences targeted are 10 that are conserved among all DENV serotype 2 strains. Our results confirm that hammerhead ribozymes can be effective in suppressing DENV in a transgenic approach, and provide an alternative or supplementary approach to proposed siRNA strategies for DENV suppression in transgenic mosquitoes.
Dissembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients
Authors: Nural Hikmet , He Ping , Beach Thomas , Sue Lucia , Xia Weiming , Shen Yong
Published: June 2009

The PARK7 gene encodes a protein, DJ-1, with several functions such as protection of cells from oxidative stress, sperm maturation and fertilization, and chaperone activity. Mutations in the PARK7 gene are associated with autosomal recessive early-onset Parkinson's disease (PD). DJ-1 has been reported to be expressed in multiple cells in the central nerve system. Here, by using both native and denatured Western blots, we examined levels of total DJ-1 and high molecular weight complexes of DJ-1 (HMW) in both the substantia nigra and cortex from rapidly autopsied 18 PD and 9 non-pathological control (NPC) brains. We have discovered that the level of total DJ-1 protein is significantly reduced in the substantia nigra in brains of sporadic PD patients. Moreover, in the PD cortex mitochondria fraction, the HMW DJ-1 complex is significantly lower than in the NPC. These results suggest abnormal DJ-1 expression levels and DJ-1 complex changes may contribute to PD pathogenesis.
Lemierre's syndrome resulting from streptococcal induced otitis media and mastoiditis: a case report
Authors: Harris Che M , Johnikin Micean , Rhodes Hope , Fuller Theresa , Rana Sohail R , Nabhani Hasan , Hussain Dulara , Kurukumbi Mohan , Jayam-Trouth Annapurni , Gajjala Jhansi , Farhat Faria , Mody Vinod
Published: June 2009

Introduction

Lemierre's syndrome is an extremely rare and almost universally fatal disease characterized as thrombophlebitis of the internal jugular venous system with subsequent metastatic infection. Fusobacterium necrophorum is the most common organism implicated in causation of Lemierre's syndrome. Group A Streptococcus has mainly been observed as a polymicrobial organism in the syndrome. We report a rare finding of a rare disease where Group A Streptococcus was the sole organism triggering Lemierre's syndrome. To our knowledge, this is only the third recorded patient with such an occurrence.

Case presentation

We describe a 9-year-old African American boy, who presented with otitis media and mastoiditis that culminated in Lemierre's syndrome. Isolates bore only Group A Streptococcus. The patient was appropriately treated and responded with full recovery from the syndrome.

Conclusion

Since Lemierre's syndrome is classically detected by clinical diagnosis, these findings should prompt clinicians to consider Group A Streptococcus as an alternative catalyst. It should be pondered that patients who present with typical Group A streptococcal infections have the possibility for developing Lemierre's syndrome. Though this complication appears to be rare, early diagnosis and prompt intervention have proven critical in survival outcome. Indeed, what would seem to be a routine case of strep throat or otitis media easily treated with antibiotics could end up being an unalterable progression to death unless Lemierre's syndrome is immediately diagnosed and treated.
Paradoxical response during antituberculous therapy in a patient discontinuing infliximab: a case report
Authors: Yoon Young Kyung , Kim Jeong Yeon , Sohn Jang Wook , Kim Min Ja , Koo Ja Seol , Choi Jai Hyun , Park Dae Won
Published: June 2009

Introduction

The use of the drug infliximab for the treatment of patients with Crohn's disease can be complicated by tuberculosis. A paradoxical reaction during antituberculosis chemotherapy and immunologic reconstitution after discontinuation of infliximab can result in severe disseminated tuberculosis.

Case presentation

A 38-year-old Korean man with severe Crohn's disease presented with fever and diffuse abdominal pain. Infliximab had been started 2 months before admission. A chest X-ray and abdominal computed tomography scan revealed numerous miliary nodules in both lung fields and microabscesses in the spleen. Given the diagnosis of disseminated tuberculosis, the infliximab therapy was discontinued and antituberculosis therapy was promptly started. Over the next 3 months, the patient was diagnosed with tuberculosis lymphadenitis on a right supraclavicular lymph node and surgical excision of the lesion was performed. With the diagnosis of a paradoxical response, anti-tuberculous therapy was continued for 12 months.

Conclusion

Our case suggests that patients who develop tuberculosis after infliximab exposure are at an increased risk of developing a paradoxical reaction. The current recommendation of discontinuing infliximab during tuberculosis treatment should be re-evaluated.
Intravascular lymphoma presenting as a specific pulmonary embolism and acute respiratory failure: a case report
Authors: Georgin-Lavialle Sophie , Darmon Michael , Galicier Lionel , Fysekidis Marinos , Azoulay Elie
Published: June 2009

Introduction

The occurrence of an intravascular lymphoma with severe pulmonary involvement mimicking pulmonary embolism is described.

Case presentation

A 38-year-old man was referred to our intensive care unit with acute respiratory failure and long lasting fever. Appropriate investigations failed to demonstrate any bacterial, viral, parasitic or mycobacterial infection. A chest computed tomography scan ruled out any proximal or sub-segmental pulmonary embolism but the ventilation/perfusion lung scan concluded that there was a high probability of pulmonary embolism. The cutaneous biopsy pathology diagnosed intravascular lymphoma.

Conclusion

Intravascular lymphoma is a rare disease characterized by exclusive or predominant growth of neoplastic cells within the lumina of small blood vessels. Lung involvement seems to be common, but predominant lung presentation of this disease is rare. In our patient, urgent chemotherapy, along with adequate supportive care allowed complete recovery.
Fetal death due to upper airway compromise complicated by thyroid storm in a mother with uncontrolled Graves' disease: a case report
Authors: Yildizhan Recep , Kurdoglu Mertihan , Adali Ertan , Kolusari Ali
Published: June 2009

Introduction

We report an unusual case of upper airway compromise complicated by thyroid storm in a pregnant woman with Graves' disease, ending with the in utero death of the fetus. This complication might have developed due to upper airway edema as a result of poorly controlled hyperthyroidism.

Case presentation

A 41-year-old Turkish woman at 27 weeks' gestation suffering from Graves' disease was referred to our emergency department with a diagnosis of respiratory arrest. She was unconscious and had been intubated. Her laboratory results were compatible with thyrotoxicosis. The patient had suffered from respiratory difficulty for a long time and had stopped using her antithyroid medications after the first trimester of pregnancy. One day before, she had visited an obstetrician because her respiratory distress had increased. At that time, her fetus was still alive. She was given oxygen therapy and then sent home. With a presumptive diagnosis of thyroid storm, she was admitted to the intensive care unit and treated with aggressive medical therapy. The baby was found to be no longer alive and was delivered vaginally after labor induction. The mother was discharged 10 days later with maintenance therapy.

Conclusion

Hyperthyroidism during pregnancy warrants very close attention and should almost always be treated with appropriate antithyroid medications. Maternal respiratory distress in such patients can be an early sign of impending upper airway compromise and thyroid storm, which can endanger the mother and fetus unless prompt and aggressive therapy is initiated.
High flow biphasic positive airway pressure by helmet – effects on pressurization, tidal volume, carbon dioxide accumulation and noise exposure
Authors: Moerer Onnen , Herrmann Peter , Hinz José , Severgnini Paolo , Calderini Edoardo , Quintel Michael , Pelosi Paolo
Published: June 2009

Introduction

Non-invasive ventilation (NIV) with a helmet device is often associated with poor patient-ventilator synchrony and impaired carbon dioxide (CO2) removal, which might lead to failure. A possible solution is to use a high free flow system in combination with a time-cycled pressure valve placed into the expiratory circuit (HF-BiPAP). This system would be independent from triggering while providing a high flow to eliminate CO2.

Methods

Conventional pressure support ventilation (PSV) and time-cycled biphasic pressure controlled ventilation (BiVent) delivered by an Intensive Care Unit ventilator were compared to HF-BiPAP in an in vitro lung model study. Variables included delta pressures of 5 and 15 cmH2O, respiratory rates of 15 and 30 breaths/min, inspiratory efforts (respiratory drive) of 2.5 and 10 cmH2O) and different lung characteristics. Additionally, CO2 removal and noise exposure were measured.

Results

Pressurization during inspiration was more effective with pressure controlled modes compared to PSV (P < 0.001) at similar tidal volumes. During the expiratory phase, BiVent and HF-BiPAP led to an increase in pressure burden compared to PSV. This was especially true at higher upper pressures (P < 0.001). At high level of asynchrony both HF-BiPAP and BiVent were less effective. Only HF-BiPAP ventilation effectively removed CO2 (P < 0.001) during all settings. Noise exposure was higher during HF-BiPAP (P < 0.001).

Conclusions

This study demonstrates that in a lung model, the efficiency of NIV by helmet can be improved by using HF-BiPAP. However, it imposes a higher pressure during the expiratory phase. CO2 was almost completely removed with HF-BiPAP during all settings.
MAPK signaling pathways in the regulation of hematopoiesis
Authors: Geest Christian R , Coffer Paul J
Published: June 2009

Relevance of mitogen-activated protein kinases ERK, JNK, and p38 in the regulation of myeloid differentiation.

The MAPKs are a family of serine/threonine kinases that play an essential role in connecting cell-surface receptors to changes in transcriptional programs. MAPKs are part of a three-component kinase module consisting of a MAPK, an upstream MEK, and a MEKK that couples the signals from cell-surface receptors to trigger downstream pathways. Three major groups of MAPKs have been characterized in mammals, including ERKs, JNKs, and p38MAPKs. Over the last decade, extensive work has established that these proteins play critical roles in the regulation of a wide variety of cellular processes including cell growth, migration, proliferation, differentiation, and survival. It has been demonstrated that ERK, JNK, and p38MAPK activity can be regulated in response to a plethora of hematopoietic cytokines and growth factors that play critical roles in hematopoiesis. In this review, we summarize the current understanding of MAPK function in the regulation of hematopoiesis in general and myelopoiesis in particular. In addition, the consequences of aberrant MAPK activation in the pathogenesis of various myeloid malignancies will be discussed.
The Mediator Complex Subunit 1 Enhances Transcription of Genes Needed for Adrenal Androgen Production
Authors: Nakamura Yasuhiro , Xing Yewei , Sasano Hironobu , Rainey William E.
Published: June 2009

There are three enzymes involved in the biosynthesis of the adrenal androgen dehydroepiandrosterone (DHEA) sulfate. Cholesterol side-chain cleavage (CYP11A1) and 17α-hydroxylase/17,20-lyase (CYP17) metabolize cholesterol into DHEA, whereas steroid sulfotransferase family 2A1 (SULT2A1) is responsible for conversion of DHEA to DHEA sulfate. We previously examined the mechanisms regulating CYP11A1, CYP17, and SULT2A1 transcription and found that each is regulated, in part, by the transcription factor GATA-6. Previous studies suggested that mediator complex subunit 1 (MED1, also called PPARBP or TRAP220) is a cofactor involved in not only the regulation of nuclear receptors but also the activation of GATA-6 transcription. Herein we demonstrated a role for MED1 in the regulation of CYP11A1, CYP17, and SULT2A1 transcription. Transient transfection assays with SULT2A1 deletion and mutation promoter constructs allowed the determination of specific the GATA-6 binding cis-regulatory elements necessary for transactivation of SULT2A1 transcription. Binding of MED1 and GATA-6 was confirmed by coimmunoprecipitation/Western analysis and chromatin immunoprecipitation assay. We demonstrated expression of MED1 mRNA and protein in the human adrenal and determined that knockdown of MED1 expression via specific small interfering RNA attenuated CYP11A1, CYP17, and SULT2A1 expression levels in H295R cells. In addition, we demonstrated that MED1 enhanced GATA-6 stimulated transcription of promoter constructs for each of these genes. Moreover, the activity of MED1 for SULT2A1 promoter was mediated by GATA-6 via the −190 GATA-binding site. These data support the hypothesis that MED1 and GATA-6 are key regulators of SULT2A1 expression, and they play important roles in adrenal androgen production.
Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement
Authors: Diamanti-Kandarakis Evanthia , Bourguignon Jean-Pierre , Giudice Linda C. , Hauser Russ , Prins Gail S. , Soto Ana M. , Zoeller R. Thomas , Gore Andrea C.
Published: June 2009

There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.
Iodine Deficiency
Authors: Zimmermann Michael B.
Published: June 2009

Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. However, about 50% of Europe remains mildly iodine deficient, and iodine intakes in other industrialized countries, including the United States and Australia, have fallen in recent years. Iodine deficiency during pregnancy and infancy may impair growth and neurodevelopment of the offspring and increase infant mortality. Deficiency during childhood reduces somatic growth and cognitive and motor function. Assessment methods include urinary iodine concentration, goiter, newborn TSH, and blood thyroglobulin. But assessment of iodine status in pregnancy is difficult, and it remains unclear whether iodine intakes are sufficient in this group, leading to calls for iodine supplementation during pregnancy in several industrialized countries. In most countries, the best strategy to control iodine deficiency in populations is carefully monitored universal salt iodization, one of the most cost-effective ways to contribute to economic and social development. Achieving optimal iodine intakes from iodized salt (in the range of 150–250 μg/d for adults) may minimize the amount of thyroid dysfunction in populations. Ensuring adequate iodine status during parenteral nutrition has become important, particularly in preterm infants, as the use of povidone-iodine disinfectants has declined. Introduction of iodized salt to regions of chronic iodine deficiency may transiently increase the incidence of thyroid disorders, but overall, the relatively small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency.
MBD4 and MLH1 are required for apoptotic induction in xDNMT1-depleted embryos
Authors: Ruzov Alexey , Shorning Boris , Mortusewicz Oliver , Dunican Donncha S. , Leonhardt Heinrich , Meehan Richard R.
Published: June 2009

Loss of the of the maintenance methyltransferase xDNMT1 during Xenopus development results in premature transcription and activation of a p53-dependent apoptotic program that accounts for embryo lethality. Here,we show that activation of the apoptotic response is signalled through the methyl-CpG binding protein xMBD4 and the mismatch repair pathway protein xMLH1. Depletion of xMBD4 or xMLH1 increases the survival rate of xDNMT1-depleted embryos, whereas overexpression of these proteins in embryos induces programmed cell death at the onset of gastrulation. MBD4 interacts directly with both DNMT1 and MLH1, leading to recruitment of the latter to heterochromatic sites that are coincident with DNMT1 localisation. Time-lapse microscopy of micro-irradiated mammalian cells shows that MLH1/MBD4 (like DNMT1) can accumulate at DNA damage sites. We propose that xMBD4/xMLH1 participates in a novel G2 checkpoint that is responsive to xDNMT1p levels in developing embryos and cells.
Protein phosphatase 2A regulates self-renewal ofDrosophilaneural stem cells
Authors: Wang Cheng , Chang Kai Chen , Somers Gregory , Virshup David , Ang Beng Ti , Tang Carol , Yu Fengwei , Wang Hongyan
Published: June 2009

Drosophila larval brain neural stem cells, also known as neuroblasts, divide asymmetrically to generate a self-renewing neuroblast and a ganglion mother cell (GMC) that divides terminally to produce two differentiated neurons or glia. Failure of asymmetric cell division can result in hyperproliferation of neuroblasts, a phenotype resembling brain tumors. Here we have identified Drosophila Protein phosphatase 2A (PP2A) as a brain tumor-suppressor that can inhibit self-renewal of neuroblasts. Supernumerary larval brain neuroblasts are generated at the expense of differentiated neurons in PP2A mutants. Neuroblast overgrowth was observed in both dorsomedial (DM)/posterior Asense-negative (PAN) neuroblast lineages and non-DM neuroblast lineages. The PP2A heterotrimeric complex,composed of the catalytic subunit (Mts), scaffold subunit (PP2A-29B) and a B-regulatory subunit (Tws), is required for the asymmetric cell division of neuroblasts. The PP2A complex regulates asymmetric localization of Numb, Pon and Atypical protein kinase C, as well as proper mitotic spindle orientation. Interestingly, PP2A and Polo kinase enhance Numb and Pon phosphorylation. PP2A, like Polo, acts to prevent excess neuroblast self-renewal primarily by regulating asymmetric localization and activation of Numb. Reduction of PP2A function in larval brains or S2 cells causes a marked decrease in Polo transcript and protein abundance. Overexpression of Polo or Numb significantly suppresses neuroblast overgrowth in PP2A mutants, suggesting that PP2A inhibits excess neuroblast self-renewal in the Polo/Numb pathway.
Cell volume regulation is initiated in mouse oocytes after ovulation
Authors: Tartia Alina P. , Rudraraju Nirmala , Richards Tiffany , Hammer Mary-Anne , Talbot Prudence , Baltz Jay M.
Published: June 2009

Fertilized mouse eggs regulate their size principally by accumulating glycine as an intracellular osmolyte using the GLYT1 (SLC6A9) transporter, a mechanism of cell volume homeostasis apparently unique to early embryos before the morula stage. However, nothing was known of cell volume regulation in oocytes before fertilization. We show here that GLYT1 is quiescent in mouse germinal-vesicle-stage oocytes but becomes fully activated within hours after ovulation is triggered. This initiates accumulation of substantial amounts of intracellular glycine in oocytes during meiotic progression, reaching a maximal level in mature eggs. Measurements of endogenous free glycine showed that there were nearly undetectable levels in ovarian germinal-vesicle-stage oocytes, but high levels were present in mature ovulated eggs and in preimplantation embryos through the two-cell stage, but not in morulae. Furthermore, intracellular glycine was regulated in response to changes in external tonicity in eggs and embryos through the two-cell stage, but not in oocytes or embryos after the two-cell stage. Before activation of GLYT1,oocytes were unable to independently regulate their volume. As GLYT1 became active, however, oocyte volume decreased substantially and oocytes gained the ability to regulate their size, which required GLYT1 activity. Before ovulation, oocyte size was instead determined by a strong adhesion to the rigid extracellular matrix of the oocyte, the zona pellucida, which was released coincident with GLYT1 activation. The ability to acutely regulate cell size is thus acquired by the oocyte only after ovulation, when it first develops glycine-dependent cell volume regulation.
Frequent incidental discovery of phaeochromocytoma: data from a German cohort of 201 phaeochromocytoma
Authors: Kopetschke Robert , Slisko Mario , Kilisli Aylin , Tuschy Ulrich , Wallaschofski Henri , Fassnacht Martin , Ventz Manfred , Beuschlein Felix , Reincke Martin , Reisch Nicole , Quinkler Marcus
Published: June 2009

Context

Adrenal and extra-adrenal phaeochromocytoma are chromaffin cell-derived tumours that are discovered due to classical symptom triad with headache, sweating and palpitations combined with persistent or paroxysmal hypertension. However, an increasing proportion of phaeochromocytoma seems to be discovered incidentally upon abdominal imaging.

Objective

To specify the exact circumstances of discovery of adrenal and extra-adrenal phaeochromocytoma.

Design and patients

Four German endocrine centres participated in this retrospective study. Medical records of 201 patients with adrenal and extra-adrenal phaeochromocytoma who were diagnosed between 1973 and 2007 were analyzed.

Results

The typical triad of symptoms was found only in 10% of cases. Ten percent of patients presented were without clinical symptoms and 6.1% were normotensive. Documented blood pressure peaks occurred in 44.1% of cases. In 24 patients (12.2%), phaeochromocytoma was malignant. Before 1985, <10% of cases were incidentally discovered, whereas thereafter the frequency was >25% (29.4% of the total study population). Patients with incidentally detected phaeochromocytoma were significantly older (53.1±1.9 vs 47.0±1.3 years; P<0.05) and often had less blood pressure peaks (37.0 vs 70.7%; P<0.001) than patients in whom the diagnosis was suspected on clinical grounds. Of phaeochromocytomas 94.4% were intra-adrenal tumours, of which 12.9% were bilateral. Bilateral tumours were significantly smaller than unilateral tumours (36.6±14.7 vs 52.5±34.3 mm; P<0.05), whereas extra-adrenal tumours had a mean diameter of 52.6±28.7 mm.

Conclusions

Owing to better availability and accessibility of imaging procedures, the number of incidentally discovered phaeochromocytoma is increasing and reaches nearly 30% in our study population. Every adrenal incidentaloma should be investigated for the presence of phaeochromocytoma.
Tuning the Threshold Voltage in Organic Field Effect Transistors by Space Charge Polarization of Gate Dielectrics
Authors: Sakai Heisuke , Konno Koudai , Murata Hideyuki
Published: June 2009

Studies of gate dielectrics in organic field effect transistors (OFETs) have been attractive because the electric properties of OFETs are susceptibly affected by the choice of the gate dielectrics. Here, we demonstrate a tunable threshold voltage in an organic field effect transistor (OFET) using an ion-dispersed gate dielectrics. By applying external electric field (Vex) to the gate dielectrics, the dispersed ions in the gate dielectrics are separated by electrophoresis and form space charge polarization. The drain current of the OFET increased over 1.9 times and the threshold voltage (Vth) decreased 22 V (from -35.1 V to -13.1 V).

The shift direction of Vth was easily tuned by the polarity of the external voltage. The dielectric permittivity of the gate dielectrics and mobility of the active layer were unchanged after the polarization of the gate dielectrics. The UV-VIS differential absorption spectra of the OFETs indicate that there is no chemical doping in the active layer of the OFETs. These results indicated the shifts of threshold voltages were originated from the polarization of gate dielectrics.
Enhanced Efficiency of CIGS Thin Film Solar Cells on Polyimide Substrates
Authors: Caballero Raquel , Kaufmann Christian A. , Eisenbarth Tobias , Eicke Axel , Unold Thomas , Klenk Reiner , Schock H.W.
Published: June 2009

The effect of the amount of Na present during the 3-stage growth of CIGS at very low temperature T2 on polyimide (PI) foils is studied. While at higher growth temperatures Na seems to impede In-Ga interdifussion, at very low temperatures it appears to further the process. An increase in Voc for a higher Na concentration can be explained by a higher net carrier concentration as measured by drive level capacitance profiling. Admittance spectroscopy measurements show shallow defects when the Na concentration increases. These results suggest that the main role of Na could be the passivation of InCu donor deep defect, in agreement with Wei's theory. Efficiencies of up to 15.1 % (0.5 cm2 active area with antireflection coating) and 13.6%, 14.1% (1 cm2 total and active area respectively without antireflection coating) for nominal T2=420° C were achieved on PI substrates so far.
Nucleation and Grain Boundaries in Thin Film CdTe/CdS Solar Cells
Authors: Major Jon D , Proskuryakov Yuri Y , Durose Ken
Published: June 2009

The early stage formation mechanisms operating during the sublimation growth of CdTe films on CdS has been evaluated using a growth interrupt methodology for deposition under 100 Torr of N2. Key stages of the growth were identified and are discussed in terms of the processes of island nucleation, island growth/coalescence, channel formation and secondary nucleation that have been reported for other materials systems. It was demonstrated that the grain size could be manipulated by means of controlling the gas pressure in the range 2 – 200 Torr, with the grain diameter increasing with pressure linearly as D (μm) = 0.027(± 0.011) × P (Torr) + 0.90(± 0.31). For a series of solar cells made using such material, the performance parameters were seen to increase with grain size up to a plateau corresponding to grains of ∼4 μm in this case. Equivalent circuit parameters for resistive components arising from grain boundaries, and the contact to the CdTe, were measured. It is considered that grain boundary barriers in CdTe are harmful to PV performance, and that the plateau in performance occurs when the grain size is increased to the level where the contact resistance is greater than that due to grain boundaries.
Preliminary Evaluation of Conductive Adhesive Tapes as Potential Interleafing Connects for Flexible Thin-Film PV Applications
Authors: Pern Fu-Jann , Jones Ryan A. , Gedvilas Lynn M. , Gessert Tim A.
Published: June 2009

Two types of commercial electrically conductive adhesive (CA) tapes, one isotropic and the other anisotropic, were investigated for their potential application as interleafing connects for flexible thin-film photovoltaic modules. The performance stability of their vacuum-laminated sample constructs between two 50-μm stainless steel (SS) foils and between the SS foil and bilayer ZnO/Mo-coated SS foil was evaluated upon damp-heat and dry-heat exposure. Preliminary results indicated that the isotropic CA tape was more stable than the anisotropic tape.