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Replacement Therapy (replacement + therapy)
Kinds of Replacement Therapy Selected AbstractsStimulated IFN, and IL-10 Secretion of Blood Mononuclear Cells in Patients on Renal Replacement Therapies Show Different Secretion PatternsARTIFICIAL ORGANS, Issue 10 2000Dominik Mark Alscher Abstract: Infection is still a leading cause of morbidity and mortality in patients on renal replacement therapy (RRT). Although the role of the immune system is of great importance, little is known about the influence of the mode of RRT to the preferential excretions of regulator cytokines of mononuclear cells. Therefore, we investigated the stimulated IFN, (Th1) and IL-10 (Th2) secretions of mononuclear cells from patients on RRT. Blood was drawn from 10 controls, 15 patients on hemodialysis (HD), 15 on peritoneal dialysis (PD), and 10 after kidney transplantation (Tx). The cells were separated, and phytohemagglutinine (PHA) was added for stimulation. After 0, 6, and 24 h, IFN, and IL-10 (pg/ml) were measured by enzyme-linked immunosorbent assay. IFN, secretion was significantly enhanced 6 (p < 0.001) and 24 h (p = 0.002) after stimulation in all groups (in mean ± SEM). The analysis of the subgroups 6 h after adding PHA showed significant differences (p = 0.0239) with the lowest IFN, in Tx (16 ± 5) and the highest in PD (79 ± 30). For IL-10, secretion was enhanced in all groups 6 h after stimulation (p < 0.0116). The lowest secretions were seen in HD (18 ± 8) and controls (27 ± 9); the highest secretions were in Tx (98 ± 20) and PD (57 ± 12). The differences between HD and Tx (p < 0.01) and HD versus PD (p = 0.05) were significant. The stimulated cytokine secretion of blood mononuclear cells is preserved with RRT. The modes of RRT could influence the pattern of cytokine secretion. Surprisingly, the cells from patients on PD showed enhanced IL-10 secretion compared to HD. Presumably, this is due to the chronic contact of peritoneal dialysis fluids with monocytes and the lymphatic system in PD. [source] Bone-Targeted Replacement Therapy for Hypophosphatasia,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008Matthew T Drake No abstract is available for this article. [source] Enzyme Replacement Therapy for Murine Hypophosphatasia,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008José Luis Millán PhD Abstract Introduction: Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5,-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6 -dependent seizures. There is no established medical treatment. Materials and Methods: Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2,/,), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, ,CT, and histomorphometry. Results:Akp2,/, mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Conclusions: Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2,/, mice. [source] Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement TherapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006Louis G Ste-Marie Abstract The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Introduction: Teriparatide {rhPTH(1-34)}, given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 ,g/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400,1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Results: Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Conclusions: Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar. [source] Effect of Hormone Replacement Therapy on Bone Quality in Early Postmenopausal WomenJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2003Ep Paschalis PhD Abstract HRT is an effective prophylaxis against postmenopausal bone loss. Infrared imaging of paired iliac crest biopsies obtained at baseline and after 2 years of HRT therapy demonstrate an effect on the mineral crystallinity and collagen cross-links that may affect bone quality. Several studies have demonstrated that hormonal replacement therapy (HRT) is an effective prophylaxis against postmenopausal bone loss, although the underlying mechanisms are still debated. Infrared spectroscopy has been used previously for analyzing bone mineral crystallinity and three-dimensional structures of collagen and other proteins. In the present study, the technique of Fourier transform infrared microscopic imaging (FTIRI) was used to investigate the effect of estrogen on bone quality (arbitrarily defined as mineral/matrix ratio, mineral crystallinity/maturity, and relative ratio of collagen cross-links [pyridinoline/deH-DHLNL]) at the ultrastructural level, in mineralized, thin tissue sections from double (before and after administration of HRT regimen; cyclic estrogen and progestogen [norethisterone acetate]) iliac crest biopsy specimens from 10 healthy, early postmenopausal women who were not on any medication with known influence on calcium metabolism. FTIRI allows the analysis of undemineralized thin tissue sections (each image analyzes a 400 × 400 ,m2 area with a spatial resolution of ,6.3 mm). For each bone quality variable considered, the after-treatment data exhibited an increase in the mean value, signifying definite changes in bone properties at the molecular level after HRT treatment. Furthermore, these findings are consistent with suppressed osteoclastic activity. [source] Hormone Replacement Therapy Dissociates Fat Mass and Bone Mass, and Tends to Reduce Weight Gain in Early Postmenopausal Women: A Randomized Controlled 5-Year Clinical Trial of the Danish Osteoporosis Prevention Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2003LB Jensen MD Abstract The aim of this study was to study the influence of hormone replacement therapy (HRT) on weight changes, body composition, and bone mass in early postmenopausal women in a partly randomized comprehensive cohort study design. A total of 2016 women ages 45,58 years from 3 months to 2 years past last menstrual bleeding were included. One thousand were randomly assigned to HRT or no HRT in an open trial, whereas the others were allocated according to their preferences. All were followed for 5 years for body weight, bone mass, and body composition measurements. Body weight increased less over the 5 years in women randomized to HRT (1.94 ± 4.86 kg) than in women randomized to no HRT (2.57 ± 4.63, p = 0.046). A similar pattern was seen in the group receiving HRT or not by their own choice. The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat. The main determinant of the weight gain was a decline in physical fitness. Women opting for HRT had a significantly lower body weight at inclusion than the other participants, but the results in the self-selected part of the study followed the pattern found in the randomized part. The change in fat mass was the strongest predictor of bone changes in untreated women, whereas the change in lean body mass was the strongest predictor when HRT was given. Body weight increases after the menopause. The gain in weight is related to a decrease in working capacity. HRT is associated with a smaller increase in fat mass after menopause. Fat gain protects against bone loss in untreated women but not in HRT-treated women. The data suggest that women's attitudes to HRT are more positive if they have low body weight, but there is no evidence that the conclusions in this study are skewed by selection bias. [source] Effects of Current and Discontinued Estrogen Replacement Therapy on Hip Structural Geometry: The Study of Osteoporotic Fractures,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2001Thomas J. Beck Abstract It is assumed that estrogen influences bone strength and risk of fractures by affecting bone mineral density (BMD). However, estrogen may influence the mechanical strength of bones by altering the structural geometry in ways that may not be apparent in the density. Repeated dual energy X-ray absorptiometry (DXA) hip scan data were analyzed for bone density and structural geometry in elderly women participating in the Study of Osteoporotic Fractures (SOF). Scans were studied with a hip structural analysis program for the effects of estrogen replacement therapy (ERT) on BMD and structural geometry. Of the 3964 women with ERT-use data, 588 used ERT at both the start and end of the ,3.5-year study, 1203 had past use which was discontinued by clinic visit 4, and 2163 women had never used ERT. All groups lost BMD at the femoral neck, but the reduced BMD among users of ERT was entirely due to subperiosteal expansion and not bone loss, whereas both bone loss and expansion occurred in past or nonusers. BMD increased 0.8%/year at the femoral shaft among ERT users but decreased 0.8%/year among nonusers. Section moduli increased at both the neck and shaft among ERT users but remained unchanged in past and nonusers. Current, but not past, use of estrogen therapy in elderly women seems to increase mechanical strength of the proximal femur by improving its geometric properties. These effects are not evident from changes in femoral neck BMD. [source] The Effects of Smoking and Nicotine Replacement Therapy on Blood PressureJOURNAL OF CLINICAL HYPERTENSION, Issue 5 2001DPhil, Thomas G. Pickering MD No abstract is available for this article. [source] Women With Primary Antibody Deficiencies Requiring IgG Replacement Therapy: Their Perception of Prenatal Care During PregnancyJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 5 2004Susanne Hansen RN Objective: To investigate how a group of women with primary antibody deficiencies (PAD) and receiving replacement therapy with IgG experienced the care they received in their prenatal clinics in relation to PAD and IgG therapy. Design: An exploratory study using a written questionnaire. Setting: The study originates from an immunodeficiency unit but evaluates care experienced at prenatal clinics. Participants: Nine women (25,43 years) attending an immunodeficiency unit and who fulfilled inclusion criteria for simultaneously having PAD, replacement IgG therapy, and full-term pregnancy (the latter within the past 5 years). Main outcome: Women's perception of the response of midwives and physicians at their prenatal clinics to their PAD and IgG therapy during pregnancy. Results: Women perceived that the obstetricians and the midwives had insufficient knowledge about PAD and IgG replacement therapy. Two women reported that their IgG therapy during pregnancy had been questioned. All nine women felt marginalized and unheard by staff regarding their PAD and need for IgG therapy. However, the women were satisfied with the checkups regarding the pregnancy as such. Conclusions: This study is the first attempt to investigate the prenatal experience of women with PAD (Search of PubMed, 1980 to present, including search terms primary immunodeficiency, pregnancy, and prenatal care). This study demonstrates that increased knowledge about PAD and IgG replacement therapy among midwives and physicians working in prenatal care clinics is needed. This can prevent misleading advice that puts the health of the mother and her fetus at risk. Sensitizing staff about this special group of women can create conditions in which women feel respected, heard, and satisfied with their prenatal care. [source] Influence of Hormone Replacement Therapy on the Accuracy of Screening MammographyTHE BREAST JOURNAL, Issue 2 2006María del Mar Vernet MD Abstract: The use of hormone replacement therapy (HRT) is currently a subject of debate because of the possibility of an increase in the incidence of breast cancer and difficulties associated with breast cancer detection. The objective of this study was to determine the influence of HRT on specificity and sensitivity in a breast cancer screening program. We found that although specificity was significantly lower in menopausal women who had ever used or were currently using HRT (93.3%) compared to HRT nonusers (94.8%) at the expense of a greater number of recalls (6.9% versus 5.6%), this difference seems to be clinically irrelevant. There were no significant differences with regard to the number of invasive procedures (2.5% in the HRT versus 2.1% in the control group). We conclude that the slight decrease in sensitivity of screening mammography in HRT users is not clinically significant in our setting, and in any case, false positives (recalled women) are diagnosed correctly with additional imaging studies without the need for invasive procedures. Most women given HRT are candidates to participate in population breast cancer screening campaigns., [source] Clomiphene Citrate and Testosterone Gel Replacement Therapy for Male Hypogonadism: Efficacy and Treatment CostTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Frederick Taylor MD ABSTRACT Introduction., The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. Aim., The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. Main Outcome Measures., The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Methods., Men receiving CC or TGRT with either Androgel® 1% or Testim® 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1,2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. Results., A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8,40 months) vs. 46 months (TGRT, range 6,149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value < 0.001). The monthly cost of Testim® 1% (5 gm daily) is $270, Androgel® 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83. Among CC patients, the average pretreatment ADAM score was 4.9 vs. 2.1 at follow up (P < 0.05). Average pretreatment ADAM sexual function domain score was 0.76 vs. 0.23 at follow up (P < 0.05). There were no adverse events reported. Conclusion., CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT. Taylor F, and Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: Efficacy and treatment cost. J Sex Med 2010;7:269,276. [source] Effects of Hormone Replacement Therapy on Heart Rate Variability in Postmenopausal WomenANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2001Aylin Yildirir M.D. Background: Hormone replacement therapy (HRT) is associated with reduced cardiovascular risk, but the underlying mechanism(s) are not fully understood. This study investigated the effects of a 6-month course of HRT on cardiac autonomic function parameters assessed by heart rate variability (HRV) in postmenopausal women. Methods: Forty-six healthy postmenopausal women (age 48 ± 5, range 40,60) with normal baseline electrocardiogram and negative exercise testing were enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate or 0.625 mg/day CEE alone were administered depending on hysterectomy status. Power spectral analysis of HRV was performed to calculate the low frequency component in absolute (LF) and normalized units (LF nu), high frequency component in absolute (HF), and normalized units (HF nu), and the LF/HF ratio. The standard deviation of RR intervals (SDNN) was calculated from the time series of RR intervals. Results: A 6-month course of HRT did not significantly alter resting heart rate (P > 0.05). The LF/HF ratio and LF nu significantly decreased after HRT (P = 0.022 and P = 0.032), whereas a significant increase was noted in the HF component of HRV (P = 0.043), indicating an improvement in cardiac autonomic function. The SDNN value, which was 28.8 ± 11.8 ms before HRT significantly increased to 35.4 ± 16.7 ms after 6 months (P = 0.011). Conclusion: Our results indicate that a 6-month course of HRT may significantly improve cardiac autonomic function parameters, a finding that could at least partly explain the potential cardiopro-tective effect(s) of HRT. A.N.E. 2001;6(4):280,284 [source] A Very Cheap Renal Replacement Therapy in the Intensive Care Unit: Is It Possible?ARTIFICIAL ORGANS, Issue 6 2010Michele Ferrannini MD No abstract is available for this article. [source] Response to Dr. Ferrannini's Letter to the Editor: A Very Cheap Renal Replacement Therapy in the Intensive Care Unit: Is It Possible?ARTIFICIAL ORGANS, Issue 6 2010Stefan Farese MD No abstract is available for this article. [source] Continuous Venovenous Renal Replacement Therapy With a Pulsatile Tubular Blood Pump: Analysis of Efficacy ParametersARTIFICIAL ORGANS, Issue 1 2006Jesús López-Herce Abstract:, A three-valve pulsatile tubular pump was used in 10 pigs weighing 9.9 ± 0.3 kg, connected to a neonatal hemofiltration (HF) circuit to analyze the parameters to determine the ultrafiltration effectiveness for venovenous continuous renal replacement therapy. Forty 30-min periods were studied to analyze the influence of the catheter diameter, purification technique (HF or hemodiafiltration), pump pulsation frequency, percentage time in diastole, percentage time in diastole in which the postpump valve was closed, and percentage time in systole in which the postfilter valve was closed, on ultrafiltrate volume and blood flow through the filter. A higher ultrafiltrate flow was achieved with a frequency of 60 bpm than with 30 bpm, a diastolic time of 65% of the total cycle versus 50%, and a blood flow of greater than 20 mL/min versus less than 20 mL/min. The ultrafiltrate flow increases in relation to the blood flow, the frequency of the pump, and the diastolic time. [source] Renal Replacement Therapy in Acute Renal FailureARTIFICIAL ORGANS, Issue 9 2003William R. Clark No abstract is available for this article. [source] The Bradykinin Response and Early Hypotension at the Introduction of Continuous Renal Replacement Therapy in the Intensive Care UnitARTIFICIAL ORGANS, Issue 12 2001J. Stoves Abstract: We assessed the relationship of certain clinical variables (including bradykinin [BK] release and dialysis membrane) to initial mean arterial pressure (MAP) reduction in 47 patients requiring continuous renal replacement therapy (CRRT) in an intensive care unit. The pretreatment MAP was 84 ± 14 mm Hg for the group as a whole. The initial MAP reduction was 11.5 (7,20) mm Hg, occurring 4 to 8 min after connection. MAP reduction was 9 (6,15) mm Hg with polyacryonitrile (PAN) membranes versus 14 (5-19) mm Hg with polysulfone (PS) (not significant). There were positive correlations between MAP reduction and BK concentration at 3 (BK3; r = 0.58, p < 0.01) and 6 (BK6; r = 0.67, p < 0.001) min with PAN but not with PS. A greater reduction in MAP was seen in patients who were not receiving inotropic support (Mann-Whitney test, p < 0.01). BK3 and BK6 values for the PAN and PS groups were not significantly different. However, BK concentrations greater than 1,000 pg/ml were only seen with PAN (6 patients, MAP reduction 27 [17,31] mm Hg). There were positive (albumin) and negative (age; acute physiology, age, and chronic health evaluation score; C-reactive protein [CRP]; calcium) correlations with BK3/BK6 in the PAN and PS groups, some of which (albumin, CRP) reached statistical significance. In summary, MAP reduction at the start of CRRT correlates with BK concentration. The similarity of response with PAN and PS suggests an importance for other clinical factors. In this study, hemodynamic instability was more likely in patients with evidence of a less severe inflammatory or septic illness. [source] Common variable immunodeficiency: 20-yr experience at a single centrePEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2009Ma Pilar Llobet Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It can present at any age in patients with a history of recurrent bacterial infections, with or without a family history of other primary immunodeficiencies (PID), and shows a wide range of clinical manifestations and immunological data. Diagnosis is based on low IgG, IgM and/or IgA levels. Delayed diagnosis and therapy can lead to bronchiectasis and malabsorption. The aim of this study was to describe a paediatric population diagnosed of CVID and its evolution in the population. Memory B-cell (MB) classification carried out in these patients was correlated with clinical manifestations and outcome. Clinical and immunological data of 22 CVID children under 18 yr treated at our centre between 1985 and 2005 are presented. Immunological studies included those for diagnosis and MB quantification. Differences in form of presentation, familial incidence and MB classification were reviewed. A statistical descriptive analysis was made. Infections were the commonest manifestation, affecting mainly respiratory (19/22) and gastrointestinal (10/22) tracts. Bronchiectasis was present in seven cases, and detected prior to CVID diagnosis in five. Replacement therapy led to a significant reduction in the number of infections. Severe complications appeared mostly in patients without MB. Patients of the same family share the same MB group. Family members had also been diagnosed of CVID in seven cases. Early diagnosis and therapy are essential to improve outcome in these patients. MB studies are useful in children to orient prognosis and further genetic studies. [source] Patterning the heart, a template for human cardiomyocyte developmentDEVELOPMENTAL DYNAMICS, Issue 7 2006Susana M. Chuva de Sousa Lopes Abstract Although in mice, the dynamics of gene expression during heart development is well characterized, information on humans is scarce due to the limited availability of material. Here, we analyzed the transcriptional distribution of Mlc-2a, Mlc-1v, Mlc-2v, and atrial natriuretic factor (ANF) in human embryonic hearts between 7 and 18 weeks of gestation and in healthy and hypertrophic adult hearts by in situ hybridization and compared expression with that in mice. Strikingly, Mlc-2a, Mlc-1v, and ANF, which are essentially chamber-restricted in mice by mid-gestation, showed a broader distribution in humans. On the other hand, Mlc-2v may prove to be an adequate ventricular marker in humans in contrast to mouse. This study emphasizes the importance of careful comparative human,animal analyses during embryonic development and adulthood, as avoiding erroneous extrapolations may be critical to develop new and successful myocardial replacement therapies. Development Dynamics 235:1994,2002, 2006. © 2006 Wiley-Liss, Inc. [source] A randomized trial of the effects of two novel nicotine replacement therapies on tobacco withdrawal symptoms and user satisfactionADDICTION, Issue 7 2010Hayden McRobbie ABSTRACT Aims To determine effects on craving, user satisfaction, and consumption patterns of two new nicotine replacement therapies (NRT) used for eight hours after overnight tobacco abstinence. Design In a within-subject, cross-over trial participants were randomly assigned Zonnic® nicotine mouth spray (1 mg/spray), Zonnic® nicotine lozenge (2.5 mg), Nicorette® gum (4 mg) and placebo lozenge on each of four study days. Setting University research unit. Participants Forty-seven dependent adult smokers. Measurements Participants rated their urges to smoke, irritability, concentration and restlessness before and during the first hour of product use on a 100-point scale. A subsample of 11 participants provided blood samples for nicotine analysis. Findings All active products reduced craving significantly more than placebo (mean reductions of 28.6, 25.8, 24.7 and 8.9 points for mouth spray, gum, lozenge and placebo). Mouth spray relieved craving faster than placebo and gum with significant reductions within five minutes of use (mean differences of ,14.5 (95% CI: ,23.0 to ,6.0) and ,10.6 (95% CI: ,19.1 to ,2.1) with placebo and gum respectively. Mouth spray produced a faster time to maximum plasma nicotine concentration (14.5 minutes, 95% CI: 8.0 to 21.0) compared to the lozenge (30.3 minutes, 95% CI: 21.1 to 39.5) and gum (45.8 minutes, 95% CI: 36.2 to 55.4). Maximum concentrations of blood nicotine were higher with mouth spray (10.0 ng/ml) and lozenge (10.8 ng/ml) compared to gum (7.8 ng/ml). Both lozenge and mouth spray were well tolerated. Conclusions The mouth spray and lozenge are at least as effective as 4 mg nicotine gum in relieving craving suggesting that they are likely to be effective in aiding smoking cessation. The mouth spray may be particularly useful for acute craving relief. [source] The future of plasma-derived clotting factor concentratesHAEMOPHILIA, Issue 2001W.K. Hoots In developed countries, preferred treatments for both haemophilia A and B have moved toward recombinant clotting factor concentrates, while plasma-derived replacement therapies are still required by many patients. Great improvements have been made in producing relatively pathogen-free clotting factor replacements from pooled plasma. The fluidity and complexity of the worldwide plasma product market are discussed in the context of the ,yin and yang' of plasma therapeutics, showing how multiple issues can influence the safety and availability of clotting factor concentrates. Use of plasma-derived products will likely continue for the next decade for patients with inhibitors, patients with von Willebrand disease, those requiring bypassing agents, in immune tolerance induction, and for treatment of rare inherited deficiencies of procoagulant or anticoagulant proteins. Furthermore, in developing countries many of the most advanced therapies are not available for the majority of haemophilia patients, and thus plasma-derived replacement concentrates will continue to be used even for noninhibitor patients. [source] A forward genetic screen for genes regulating mineralized tooth and bone formation in zebrafish (Danio rerio)JOURNAL OF APPLIED ICHTHYOLOGY, Issue 2 2010P. C. Yelick Summary Our laboratory studies craniofacial skeletal and tooth regeneration. One approach we are using is to exploit the zebrafish model via a large-scale, forward genetic, chemical N-ethyl-nitroso-urea (ENU) mutagenesis screen to identify genes regulating mineralized craniofacial, axial and dental development. The fact that zebrafish continuously regenerate their teeth makes them an extremely useful model to study tooth regeneration. Our goal is to identify and characterize molecular genetic signaling pathways regulating these processes, which can be manipulated via targeted gene delivery strategies. Through these efforts, we hope to eventually define methods for effective, clinically relevant bone and tooth replacement therapies in humans. Here, we describe our studies using the zebrafish model, which are proving to be useful for the identification and characterization of genes regulating mineralized tissue formation, regeneration, and homeostasis. Although preliminary at the present time, we anticipate the elucidation of novel signaling pathways regulating bone and tooth regeneration, which will eventually facilitate the repair of human skeletal and dental dysplasias. [source] Stemness, fusion and renewal of hematopoietic and embryonic stem cellsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2003S. Constantinescu Abstract Development of replacement cell therapies awaits the identification of factors that regulate nuclear reprogramming and the mechanisms that control stem cell renewal and differentiation. Once such factors and signals will begin to be elucidated, new technologies will have to be envisaged where uniform differentiation of adult or embryonic stem cells along one differentiation pathway can be induced. Controlled differentiation of stem cells will require the engineering of niches and extracellular signal combinations that would amplify a particular signaling network and allow uniform and selective differentiation. Three recent advances in stem cell research open the possibility to approach engineering studies for cell replacement therapies. Fusion events between stem cells and adult cells or between adult and embryonic stem cells have been shown to result in altered fates and nuclear reprogramming of cell hybrids. Hematopoietic stem cells were shown to require Wnt signaling in order to renew. The purification of Wnt proteins would allow their use as exogenous purified cytokines in attempts to amplify stem cells before bone marrow transplantation. The homeodomain protein Nanog has been shown to be crucial for the embryonic stem cell renewal and pluripotency. However, the cardinal question of how stemness is preserved in the early embryo and adult stem cells remains opened. [source] Neural crest-derived stem cells display a wide variety of characteristicsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Narihito Nagoshi Abstract A recent burst of findings has shown that neural crest-derived stem cells (NCSCs) can be found in diverse mammalian tissues. In addition to their identification in tissues that are known to be derived from the neural crest, recent studies have revealed NCSCs in tissues that are not specifically derived from the neural crest, such as bone marrow. NCSCs can express a wide range of characteristics, and which properties are expressed mainly depends on their tissue sources and the ontogenic stage of the animal. The identification of NCSCs in various tissues opens an entirely new avenue of approach to developing autologous cell replacement therapies for use in regenerative medicine. In this review, we discuss the origin, migration, and lineage potential of NCSCs from various mammalian tissue sources. J. Cell. Biochem. 107: 1046,1052, 2009. © 2009 Wiley-Liss, Inc. [source] Adult cerebrospinal fluid inhibits neurogenesis but facilitates gliogenesis from fetal rat neural stem cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2009Judith Buddensiek Abstract Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Administration of NSCs into the cerebrospinal fluid (CSF) offers a nontraumatic transplantation method into the brain. However, cell survival and intraparenchymal migration of the transplants are limited. Furthermore, CSF was recently reported to be an important milieu for controlling stem cell processes in the brain. We studied the effects of adult human leptomeningeal CSF on the behavior of fetal rat NSCs. CSF increased survival of NSCs compared with standard culture media during stem cell maintenance and differentiation. The presence of CSF enhanced NSC differentiation, leading to a faster loss of self-renewal capacity and faster and stronger neurite outgrowth. Some of these effects (mainly cell survival, neurite brancing) were blocked by addition of the bone morphogenic protein (BMP) inhibitor noggin. After differentiation in CSF, significantly fewer MAP2ab+ neurons were found, but there were more GFAP+ astroglia compared with standard media. By RT-PCR analysis, we determined a decrease of mRNA of the NSC marker gene Nestin but an increase of Gfap mRNA during differentiation up to 72 hr in CSF compared with standard media. Our data demonstrate that adult human leptomeningeal CSF enhances cell survival of fetal rat NSCs during proliferation and differentiation. Furthermore, CSF provides a stimulus for gliogenesis but inhibits neurogenesis from fetal NSCs. Our data suggest that CSF contains factors such as BMPs regulating NSC behavior, and we hypothesize that fast differentiation of NSCs in CSF leads to a rapid loss of migration capacity of intrathecally transplanted NSCs. © 2009 Wiley-Liss, Inc. [source] Evaluation of human fetal neural stem/progenitor cells as a source for cell replacement therapy for neurological disorders: Properties and tumorigenicity after long-term in vitro maintenanceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Daisuke Ogawa Abstract It is expected that human neural stem/progenitor cells (hNS/PCs) will some day be used in cell replacement therapies. However, their availability is limited because of ethical issues, so they have to be expanded to obtain sufficient amounts for clinical application. Moreover, in-vitro-maintained hNS/PCs may have a potential for tumorigenicity that could be manifested after transplantation in vivo. In the present study, we demonstrate the in vitro and in vivo properties of long-term-expanded hNS/PCs, including a 6-month bioluminescence imaging (BLI) study of their in vivo tumorigenicity. hNS/PCs cultured for approximately 250 days in vitro (hNS/PCs-250) exhibited a higher growth rate and greater neurogenic potential than those cultured for approximately 500 days in vitro (hNS/PCs-500), which showed greater gliogenic potential. In vivo, both hNS/PCs-250 and -500 differentiated into neurons and astrocytes 4 weeks after being transplanted into the striatum of immunodeficient mice, and hNS/PCs-250 exhibited better survival than hNS/PCs-500 at this time point. We also found that the grafted hNS/PCs-250 survived stably and differentiated properly into neurons and astrocytes even 6 months after the surgery. Moreover, during the 6-month observation period by BLI, we did not detect any evidence of rapid tumorigenic growth of the grafted hNS/PCs, and neither PCNA/Ki67-positive proliferating cells nor significant malignant invasive features were detected histologically. These findings support the idea that hNS/PCs may represent a nontumorigenic, safe, and appropriate cell source for regenerative therapies for neurological disorders. © 2008 Wiley-Liss, Inc. [source] The use of the nicotine inhaler in smoking cessationJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 3 2006CCRN (Staff Nurse), Jenny Sigel Burkett RN Abstract Purpose: To raise awareness among nurse practitioners (NPs) about the nicotine inhaler by providing clinical and practical information about the use of the nicotine inhaler as a treatment option for smoking cessation. Data sources: This included data-based and review articles in the medical literature, tobacco use and dependence clinical practice guideline, and Medline and Cinahl search engines. Criteria for search keywords were "nicotine inhaler" and "nicotine replacement therapy." Initial search was done in December 2004. Conclusions: The nicotine inhaler has been tested as safe and efficacious in the treatment of tobacco cessation. Clinical trials show the nicotine inhaler to be useful alone or as an adjunct to other pharmacological therapies. Current national guidelines recommend that the nicotine inhaler be used in smoking cessation therapy. Implications for practice: The nicotine inhaler is appropriate for many different smokers, including certain types of cardiac patients. NPs can include the nicotine inhaler in a group of nicotine replacement therapies to ensure that smokers are successful in tobacco cessation. [source] Thrombosis in inherited factor VII deficiencyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2003G. Mariani Summary., Thrombosis in congenital factor (F) VII deficiency was investigated through extensive phenotypic and molecular-genetic studies. Patients with a history of thrombosis among 514 entries in the FVII Deficiency Study Group database were evaluated. Thrombotic events were arterial in one case, disseminated intravascular coagulation in another and venous in seven. Gene mutations were characterized in eight patients: three were homozygous, three compound heterozygous and two heterozygous. FXa and IIa generation assays were consistent with the genetic lesions. One patient was heterozygous for the FV Leiden and one for the FIIG20210A mutation. In seven patients, surgical interventions and/or replacement therapies had a close temporal relationship with thrombosis, while in the remaining, events were apparently spontaneous. Thromboses were not associated with any specific age, phenotype, mutation zygosity or thrombophilic abnormalities. In particular, severe FVII deficiency did not seem to offer protection from strong thrombosis risk factors such as surgery and replacement therapy. [source] Cognitive impulsivity in Parkinson's disease patients: Assessment and pathophysiology,MOVEMENT DISORDERS, Issue 16 2009Gabriel Robert MSc Abstract Impulsivity may be induced by therapeutic interventions (dopamine replacement therapies and sub-thalamic nucleus (STN) stimulation) in patients with Parkinson's disease (PD). The present review has two goals. First, to describe the most frequently encountered facets of cognitive impulsivity and to stress the links between cognitive impulsivity and aspects such as reward-related decision making, risk-taking, and time-processing in healthy population. The most widely used related cognitive impulsivity paradigms are presented. Second, to review the results of studies on cognitive impulsivity in healthy volunteers and in patients with PD, the latter support the applicability and clinical relevance of this construct in PD population. Data show that PD treatments may favor impulsivity via different mechanisms. Suggestions on the roles of dopamine and STN in the pathophysiology of cognitive impulsivity are proposed. © 2009 Movement Disorder Society [source] Excessive dopamine neuron loss in progressive supranuclear palsyMOVEMENT DISORDERS, Issue 4 2008Karen E. Murphy BSc(Hons) Abstract Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) differ in their response to dopaminergic replacement therapies, despite having a similar degree of neuronal degeneration in the dopaminergic substantia nigra. We observed more widespread dopamine neuron loss in the extranigral A10 midbrain cell groups in PSP compared with PD. These cell groups innervate subcortical and cortical regions and may be required for adequate response to levodopa therapy. © 2007 Movement Disorder Society [source] | ||||||||||||||||||||||||||||||||||||||||