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11.
Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study
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Aditi Shastri Anjali Budhathoki Stefan K. Barta Noah Kornblum Olga Derman Ramakrishna Battini Radha Raghupathy Amit K. Verma Paul S. Frenette Ira Braunschweig Murali Janakiram 《American journal of hematology》2017,92(10):1047-1051
Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 106 CD34+ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 106 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 106 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation. 相似文献
12.
Dual treatment with sofosbuvir plus ribavirin is as effective as triple therapy with pegylated interferon plus sofosbuvir plus ribavirin in predominant genotype 3 patients with chronic hepatitis C
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13.
14.
K Radha Krishna Murthy 《Japanese heart journal》1982,23(5):835-842
Acute myocarditis is produced in rabbits with scorpion (Buthus tamulus) (a common scorpion found in South India) venom. Acute myocarditis is confirmed by changes in the ECG taken before and after venom injection. The atrial and ventricular sarcolemmal Na+-K+ ATPase, Mg++ ATPase, and Ca++ ATPase activities are assayed in control and venom injected rabbits. Atrial and ventricular sarcolemmal ATPase activities are similar in control animals. A significant reduction in atrial Ca++ ATPase activity is seen in venom treated rabbits. Animals injected with 2 mg/Kg venom exhibited significant increases in Mg++ ATPase and Ca++ ATPase activities in the ventricular sarcolemma. However, significant reductions in Na+-K+ ATPase and Ca++ ATPase activities are observed in ventricular tissue from rabbits treated with 4 mg/Kg of venom. 相似文献
15.
Frances M. Sobierajski Graeme M. Purdy Charlotte W. Usselman Rachel J. Skow Marina A. James Radha S. Chari Rshmi Khurana Michael K. Stickland Sandra T. Davidge Maureen Devolin Craig D. Steinback Margie H. Davenport 《The Canadian journal of cardiology》2018,34(4):485-491
Background
Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy.Methods
Fifty-eight third trimester (31.9 ± 3.0 weeks) normotensive pregnant women (31.2 ± 2.8 years) were tested. Heart rate (electrocardiogram) and blood pressure (systolic blood pressure and MAP; finger photoplethysmography) were collected on a beat-by-beat basis, and averaged over 3 minutes of rest. Spontaneous cBRG was calculated as the slope of the relationship between fluctuations in systolic blood pressure and heart rate. Objective measures of MVPA and sedentary behaviour were collected over a 7-day period using an ActiGraph accelerometer (model wGTX3-BT; ActiGraph LLC, Pensacola, FL).Results
Participants spent 67.5 ± 7.9% of waking hours engaged in sedentary behaviour, and performed 68.6 ± 91.9 minutes of MVPA per week. Sedentary behaviour was not related to cBRG (r = ?0.035; P = 0.793) or MAP (r = ?0.033; P = 0.803). However, MVPA was positively associated with cBRG (r = 0.315; P = 0.016), but not MAP (r = ?0.115; P = 0.389). The association between MVPA and cBRG remained significant after controlling for age, pre-pregnancy body mass index, gestational age, and wear time (r = 0.338; P = 0.013), indicating that women who engaged in greater amounts of MVPA showed increased cBRG.Conclusions
Our data suggest that increased MVPA, but not necessarily reduced sedentary behaviour, might be beneficial for reflex control of blood pressure during pregnancy. 相似文献16.
Shelley A. Wiechman Kara McMullen Gretchen J. Carrougher Jame A. Fauerbach Colleen M. Ryan David N. Herndon Radha Holavanahalli Nicole S. Gibran Kimberly Roaten 《Archives of physical medicine and rehabilitation》2018,99(7):1311-1317
Objective
To identify important sources of distress among burn survivors at discharge and 6, 12, and 24 months postinjury, and to examine if the distress related to these sources changed over time.Design
Exploratory.Setting
Outpatient burn clinics in 4 sites across the country.Participants
Participants who met preestablished criteria for having a major burn injury (N=1009) were enrolled in this multisite study.Interventions
Participants were given a previously developed list of 12 sources of distress among burn survivors and asked to rate on a 10-point Likert-type scale (0=no distress to 10=high distress) how much distress each of the 12 issues was causing them at the time of each follow-up.Main Outcomes Measures
The Medical Outcomes Study 12-Item Short-Form Health Survey was administered at each time point as a measure of health-related quality of life. The Satisfaction With Appearance Scale was used to understand the relation between sources of distress and body image. Finally, whether a person returned to work was used to determine the effect of sources of distress on returning to employment.Results
It was encouraging that no symptoms were worsening at 2 years. However, financial concerns and long recovery time are 2 of the highest means at all time points. Pain and sleep disturbance had the biggest effect on ability to return to work.Conclusions
These findings can be used to inform burn-specific interventions and to give survivors an understanding of the temporal trajectory for various causes of distress. In particular, it appears that interventions targeted at sleep disturbance and high pain levels can potentially effect distress over financial concerns by allowing a person to return to work more quickly. 相似文献17.
Intrahepatic portal venopathy leads to various entities that are important causes of portal hypertension. Noncirrhotic portal fibrosis (NCPF) occurs in the Indian subcontinent, whereas idiopathic portal hypertension (IPH) occurs in Japan although the pathogenesis and presentation of both are similar. NCPF presents mainly with upper gastrointestinal bleeding; IPH presents with massive splenomegaly. The liver functions are preserved. Wedged hepatic venous pressure is normal, but portal venous pressure is high indicating a presinusoidal block. Patients are best managed with endoscopic therapy or surgery, with better results than in patients with cirrhosis. Nodular regenerative hyperplasia is a histological diagnosis characterized by development of nodules in the liver due to uneven perfusion of the portal venous blood. These patients may develop portal hypertension and if they bleed would require treatment as in NCPF/IPH. Schistosomiasis produces portal hypertension by the development of fibrous tissue around the portal veins as a response to schistosome eggs. Gratifying results have been reported with praziquantel therapy. Rarely sarcoidosis and chronic biliary obstruction may also produce portal venopathy. 相似文献
18.
Dhiman RK Sawhney MS Chawla YK Das G Ram S Dilawari JB 《Digestive diseases and sciences》2000,45(8):1549-1552
To investigate the role of lactulose in the treatment of cirrhotic patients with subclinical hepatic encephalopathy (SHE), 40 cirrhotic patients, 33 males and 7 females, were included in the study. The diagnosis of SHE was made by quantitative psychometric tests including the number connection test (NCT), figure connection test (FCT) parts A and B, and two performance subtests of Wechsler adult intelligence scale, ie, picture completion (PC) and block design (BD) tests. SHE was diagnosed in 26 (65%) of 40 patients. Of these 26 patients, 14 patients were randomized to treatment group (lactulose 30–60 ml/day for three months, SHE-L) and 12 patients to no treatment group (no lactulose, SHE-NL). Psychometric tests were repeated in all patients in both groups and in six patients with no SHE (group NSHE, N = 14) after three months. The mean scores and number of the abnormal psychometric tests at entry were significantly higher in patients in groups SHE-L and SHE-NL than in patients in group NSHE; however, there was no significant difference between SHE-L and SHE-NL. The mean number of the abnormal psychometric tests decreased in patients in group SHE-L after three months of treatment with lactulose (2.9 ± 0.9 vs 0.8 ± 1.2; P = 0.004); however, there was no change in patients in group SHE-NL after three months (3.7 ± 1.5 vs 3.5 ± 1.3; P = NS). While SHE improved in 8 of 10 patients in group SHE-L, none of the patients in group SHE-NL improved after three months of follow-up (P < 0.001). Two patients in group SHE-NL also developed overt encephalopathy during the study period. We conclude that lactulose treatment in cirrhotic patients with SHE is effective. 相似文献
19.
Samantha R. Slight Leticia Monin Radha Gopal Lyndsay Avery Marci Davis Hillary Cleveland Tim D. Oury Javier Rangel-Moreno Shabaana A. Khader 《The American journal of pathology》2013,183(5):1397-1404
IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10–deficient mice (Il10−/−), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10−/−-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain.Francisella tularensis, a facultative intracellular bacterium, because of its infectious nature and the severe disease caused by low doses of airborne bacteria, has been classified as a category A select bioterrorism agent.1 Infection in humans is caused by two main subspecies, F. tularensis (type A) and Francisella holarctica (type B).2 An F. tularensis live vaccine strain (LVS) has been developed from the F. tularensis B strain as an experimental vaccine, but is not licensed for use in humans.1
F. tularensis LVS has been used as a representative attenuated model to address the immune requirements for protection against Francisella. By using this model, the importance of IL-12 in driving interferon γ (IFN-γ) and T-helper cell 1 (Th1) responses in immunity to F. tularensis LVS infection is well described.3–5 In contrast, IL-17 is generally thought to play a role in protection against extracellular, but not intracellular, pathogens.6 However, we and others recently identified a protective role for IL-17 in the induction of cellular immunity to F. tularensis LVS pulmonary infection,7–9 by driving the production of IFN-γ through IL-12 induction.7 IL-17 is a proinflammatory cytokine also known to induce chemokines, such as keratinocyte chemoattractant, macrophage inflammatory protein 2 (MIP-2), and granulocyte colony-stimulating factor (G-CSF), to mediate granulopoiesis, neutrophil recruitment, and inflammation.6 Accordingly, the absence of IL-17 during F. tularensis LVS pulmonary infection also results in decreased induction of G-CSF and MIP-2, as well as decreased accumulation of neutrophils and lung inflammation.7 Neutrophil depletion alone does not affect bacterial control after pulmonary infection with F. tularensis LVS,10 suggesting that the role for IL-17 in driving Th1 responses, and not neutrophil recruitment, was the primary immune mechanism mediating protection in this model.7 These data together suggest that both IL-17 and IFN-γ are required for generating protective immunity to pulmonary F. tularensis LVS infection.IL-10 is an anti-inflammatory cytokine best studied for its inhibitory effects on IL-12 production and down-regulation of Th1 responses.11 Accordingly, IL-10–deficient mice show enhanced protection in models of intracellular bacterial infections, such as Mycobacterium tuberculosis12 and Listeria monocytogenes.13 In addition, in a cutaneous model of F. tularensis LVS infection, IL-10–deficient mice exhibit increased protection, and this was reversed when IL-17 was depleted.14 In contrast to these published studies, in the current study, we report that after pulmonary infection with F. tularensis LVS, mice deficient in IL-10 (Il10−/−) exhibit increased mortality. We clearly demonstrate that the increased mortality in the Il10−/−-infected mice is not associated with loss of protective immunity, because bacterial burden between wild-type and Il10−/− mice is similar, but is caused by exacerbated inflammation and increased lung pathology. We demonstrate that the exacerbated inflammation observed in Il10−/−-infected mice is the result of unrestrained IL-17 production and IL-17–dependent recruitment of neutrophils and resulting lung pathology. These data together suggest that, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis LVS,7,9 IL-17 production is tightly regulated by anti-inflammatory cytokines, such as IL-10. Our studies highlight how inflammatory cytokines, such as IL-17, can be beneficial for host protection, but when produced unrestrained, can mediate host pathology. 相似文献
20.
Impact of the basic skin cancer triage curriculum on providers’ skin cancer control practices
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Mikkilineni R Weinstock MA Goldstein MG Dube CE Rossi JS 《Journal of general internal medicine》2001,16(5):302-307
OBJECTIVE: To evaluate the effect of a 2-hour, multicomponent educational intervention on provider skin cancer control practices. DESIGN: Nonrandomized intervention study. The intervention was a 2-hour curriculum designed to augment provider skin cancer control practices through instruction in basic skin cancer triage (BSCT) and a brief summary of skin cancer epidemiology, prevention, and counseling. SETTING: Five staff-model health maintenance organizations in southeastern New England. PARTICIPANTS: Convenience sample of primary care providers. Providers older than age 75, individuals in practice for less than 1 year, or individuals planning to retire in the next 2 years were excluded from the study. Twenty-two of 28 participants completed the study. RESULTS: Providers completed preintervention and postintervention surveys asking them to rate their attitudes towards skin examination and skin cancer counseling and to rate the frequency of their skin cancer control practices, using 5-point Likert scales. We independently assessed provider behavior through surveys of their patients, eliciting information on provider practices before and after BSCT participation. Following participation in the curriculum, there was significant improvement in provider attitudes towards the total body skin examination but not towards skin cancer prevention counseling. Significant increases in provider self- reported skin cancer control practices during an initial visit with a new patient (2.17 to 3.21, P <.0001) and a routine visit with a patient at high risk for melanoma (2.15 to 3.00, P <.0001) were demonstrated. Analysis of the patient exit interviews independently confirmed these changes in practice patterns. CONCLUSIONS: The study results suggest that the BSCT curriculum may be a useful tool in increasing the practice of skin cancer control measures by primary care providers. 相似文献