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81.
Voiding and sexual dysfunction after deep rectal resection and total mesorectal excision 总被引:3,自引:0,他引:3
Sterk P Shekarriz B Günter S Nolde J Keller R Bruch HP Shekarriz H 《International journal of colorectal disease》2005,20(5):423-427
OBJECTIVE: Voiding and sexual dysfunction after deep rectal resection have been described with various frequencies in the literature. In this study, we prospectively evaluated the baseline preoperative voiding and sexual function in a cohort of patients undergoing deep rectal resection with mesorectal excision to determine any pre-existing abnormalities. Postoperatively, we sought first to determine the frequency of a urinary or sexual dysfunction, secondly whether there is a time-dependent change of a dysfunction and thirdly whether there is a relationship between postoperative urological dysfunction and the patient's age. PATIENTS AND METHODS: Fifty-two patients (36 men and 16 women) with a primary rectal carcinoma were prospectively examined directly before and after the operation, as well after the third and sixth postoperative month. The preoperative urological evaluation consisted of a careful voiding and sexual history, uroflowmetry and a sonographic residual urine determination. A detailed sexual history was obtained via the use of a questionnaire. RESULTS: Urological dysfunction: Preoperatively, 49 of the 52 patients had a completely normal bladder function and three patients had post void residual >100 ml. Postoperatively, 12 of the 49 patients with normal preoperatively urinary function had voiding dysfunction, but only four male patients had residual urine in the third postoperative month. Therefore, in about 90% of the patients, postoperative bladder function became normal and only 10% suffered from vesical denervation after 6 months. We could not determine a relationship between the degree of bladder dysfunction and the patient's age due to a relatively small patient cohort in this study. Sexual dysfunction: Preoperatively, 36 (seven women, 29 men) of the 52 patients were potent and had regular sexual intercourse. Eleven men specified a limited erection, but all had occasional sexual intercourse. One of the potent men experienced no ejaculation. Postoperatively, eight of the 29 men were impotent and two of the 29 men experienced retrograde ejaculation. Therefore, 30% of the preoperatively potent men had sexual dysfunction postoperatively. There was no correlation between the postoperative impotence and the age of the patients at the time of surgery. Although it is likely that the potency may diminish with advanced age, the incidence of impotence was not higher in the older patients of our study. CONCLUSIONS: The results of our study underline the importance of risk estimation for possible postoperative urological dysfunction by means of preoperative urologic evaluation in this patient collective. Of patients with postoperative bladder dysfunction, 90% improved within 6 months after surgery and only 10% continued to have bladder dysfunction beyond 6 months, indicating irreversible nerve damage. 相似文献
82.
Dimberg A Rylova S Dieterich LC Olsson AK Schiller P Wikner C Bohman S Botling J Lukinius A Wawrousek EF Claesson-Welsh L 《Blood》2008,111(4):2015-2023
Selective targeting of endothelial cells in tumor vessels requires delineation of key molecular events in formation and survival of blood vessels within the tumor microenvironment. To this end, proteins transiently up-regulated during vessel morphogenesis were screened for their potential as targets in antiangiogenic tumor therapy. The molecular chaperone alphaB-crystallin was identified as specifically induced with regard to expression level, modification by serine phosphorylation, and subcellular localization during tubular morphogenesis of endothelial cells. Small interfering RNA-mediated knockdown of alphaB-crystallin expression did not affect endothelial proliferation but led to attenuated tubular morphogenesis, early activation of proapoptotic caspase-3, and increased apoptosis. alphaB-crystallin was expressed in a subset of human tumor vessels but not in normal capillaries. Tumors grown in alphaB-crystallin(-/-) mice were significantly less vascularized than wild-type tumors and displayed increased areas of apoptosis/necrosis. Importantly, tumor vessels in alphaB-crystallin(-/-) mice were leaky and showed signs of caspase-3 activation and extensive apoptosis. Ultrastructural analyses showed defective vessels partially devoid of endothelial lining. These data strongly implicate alphaB-crystallin as an important regulator of tubular morphogenesis and survival of endothelial cell during tumor angiogenesis. Hereby we identify the small heat shock protein family as a novel class of angiogenic modulators. 相似文献
83.
Sun Z Wu J Fujii H Wu J Li SH Porozov S Belleli A Fulga V Porat Y Li RK 《European journal of heart failure》2008,10(6):525-533
BACKGROUND: We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro. AIMS: In the present study, we used a nude rat model of ischaemic cardiomyopathy to compare the efficacy of intramyocardial and intracoronary ACP implantation, and to evaluate effects on cardiac function, scar size and angiogenesis. METHODS AND RESULTS: Adult nude rats underwent coronary artery ligation. Six days later, ACPs (characterized in vitro prior to implantation) or culture media were injected directly into the ischaemic myocardial region or into the coronary artery via the aorta. Cardiac function was measured by echocardiography prior to and at 2 and 4 weeks after implantation. Scar morphology, cell engraftment, and myocardial angiogenesis were evaluated at 4 weeks. Two and four weeks after implantation, cardiac function declined in both of the control groups but improved in both the intramyocardial and intracoronary ACP groups. Significant reductions in myocardial scar area were only observed in the intramyocardial ACP group, while increases in blood vessel density, which were observed in all ACP recipients, were greatest in the intracoronary ACP group. CONCLUSIONS: Human ACPs, delivered via intramyocardial or intracoronary injection, engrafted into damaged cardiac tissue and improved cardiac function within 4 weeks through effects on scar morphology and blood vessel formation. 相似文献
84.
Larisa Rudenko Julia Desheva Sergey Korovkin Alexander Mironov Andrey Rekstin Elena Grigorieva Svetlana Donina Alexandra Gambaryan Anton Katlinsky 《Influenza and other respiratory viruses》2008,2(6):203-209
Objective Our studies aimed to evaluate in clinical trials the safety and immunogenicity of an H5 live influenza vaccine candidate obtained using classical reassortment techniques from a low pathogenicity avian influenza (LPAI) A/Duck/Potsdam/1402‐6/86(H5N2) virus and the cold‐adapted (ca) donor strain A/Leningrad/134/17/57(H2N2). Methods During Phase I–II clinical trials, volunteers received intranasally two doses of reassortant influenza vaccine strain A/17/Duck/Potsdam/86/92 (H5N2) 21 days apart. Clinical examination of all vaccinees was conducted 7 days post‐vaccination. Serum antibody responses were measured by hemagglutination‐inhibition and microneutralization and local antibodies were estimated using an enzyme‐linked immunosorbent assay test. Results The vaccine was safe and of low reactogenicity with no febrile reactions. After revaccination 47·1–54·8% of subjects showed ≥fourfold seroconversions of Hamagglutination inhibition (HAI) antibodies to the hemagglutinin (HA) antigen of the A/17/Duck/Potsdam/86/92 (H5N2) virus and 29·4–30·8% were seroconverted to the HA antigen of the reverse genetics reassortant A/Indonesia/05/2005 × PR8 IBCDC‐RG (H5N1). Virus‐neutralizing antibody levels in sera of volunteers were similar to those shown in HAI test. The virus‐specific nasal IgA antibody response after two vaccine doses demonstrated significant increases of ≥fourfold rise SIgA antibodies (65%) geometrical mean titers (16·0) and a rise in SIgA antibodies (2·8) compared with one dose. Conclusion The live attenuated influenza vaccine candidate prepared using the LPAI A(H5N2) strain was well tolerated and elicited serum and local immune responses. There was evident cross‐reactivity to the A(H5N1) strain in the HAI test. 相似文献
85.
Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors 总被引:4,自引:3,他引:4 下载免费PDF全文
Chen W Antonenko S Sederstrom JM Liang X Chan AS Kanzler H Blom B Blazar BR Liu YJ 《Blood》2004,103(7):2547-2553
Type 1 interferon-producing cells (IPCs), also known as plasmacytoid dendritic cell (DC) precursors, represent the key effectors in antiviral innate immunity and triggers for adaptive immune responses. IPCs play important roles in the pathogenesis of systemic lupus erythematosus (SLE) and in modulating immune responses after hematopoietic stem cell transplantation. Understanding IPC development from hematopoietic progenitor cells (HPCs) may provide critical information in controlling viral infection, autoimmune SLE, and graft-versus-host disease. FLT3-ligand (FLT3-L) represents a key IPC differentiation factor from HPCs. Although hematopoietic cytokines such as interleukin-3 (IL-3), IL-7, stem cell factor (SCF), macrophage-colony-stimulating factor (M-CSF), and granulocyte M-CSF (GM-CSF) promote the expansion of CD34+ HPCs in FLT3-L culture, they strongly inhibit HPC differentiation into IPCs. Here we show that thrombopoietin (TPO) cooperates with FLT3-L, inducing CD34+ HPCs to undergo a 400-fold expansion in cell numbers and to generate more than 6 x 10(6) IPCs per 10(6) CD34+ HPCs within 30 days in culture. IPCs derived from HPCs in FLT3-L/TPO cultures display blood IPC phenotype and have the capacity to produce large amounts of interferon-alpha (IFN-alpha) and to differentiate into mature DCs. This culture system, combined with the use of adult peripheral blood CD34+ HPCs purified from G-CSF-mobilized donors, permits the generation of more than 10(9) IPCs from a single blood donor. 相似文献
86.
Robins T Barbaro M Lajic S Wedell A 《The Journal of clinical endocrinology and metabolism》2005,90(4):2148-2153
More than 90% of all cases of congenital adrenal hyperplasia result from steroid 21-hydroxylase (CYP21) gene mutations. Around 95% of these are either gene deletions or any of nine sequence aberrations that have been transferred from the nearby pseudogene through apparent gene conversions. One such recurrent pseudogene-derived mutation is Cluster E6, a combination of three amino acid substitutions in exon 6: I236N, V237E, and M239K. Cluster E6 is associated with the most severe, salt-wasting form of congenital adrenal hyperplasia. We studied the functional consequences of each missense mutation individually as well as the combined effect of the three mutations comprising Cluster E6. V237E abolished enzyme function and is thus a null mutation, whereas very low but measurable activity remained for I236N. M239K, on the other hand, had no effect on enzyme activity and consequently does not contribute to the disease. Although no allele has been reported yet to contain only one or two missense mutations of Cluster E6, it is a well-known feature of CYP21 that it can harbor many different combinations of pseudogene-derived mutations. The exclusion of M239K as a disease-causing mutation is thus relevant when designing protocols for genetic diagnostics. 相似文献
87.
88.
Svetlana Grabauskiene Edward J. Bergeron Guoan Chen Dafydd G. Thomas Thomas J. Giordano David G. Beer Meredith A. Morgan Rishindra M. Reddy 《The Journal of surgical research》2014
Background
When presenting with advanced stage disease, lung cancer patients have <5% 5-y survival. The overexpression of checkpoint kinase 1 (CHK1) is associated with poorer outcomes and may contribute to therapy resistance. Targeting CHK1 with small-molecule inhibitors in p53 mutant tumors might improve the effectiveness of chemotherapy and radiotherapy in non–small cell lung cancer (NSCLC).Methods
We evaluated CHK1 messenger RNA and protein levels in multiple NSCLC cell lines. We assessed cell line sensitization to gemcitabine, pemetrexed, and radiotherapy by CHK1 inhibition with the small molecule AZD7762 using proliferation and clonogenic cell survival assays. We analyzed CHK1 signaling by Western blotting to confirm that AZD7762 inhibits CHK1.Results
We selected two p53 mutant NSCLC cell lines with either high (H1299) or low (H1993) CHK1 levels for further analysis. We found that AZD7762 sensitized both cell lines to gemcitabine, pemetrexed, and radiotherapy. Chemosensitization levels were greater, however, for the higher CHK1 protein expressing cell line, H1299, when compared with H1993. Furthermore, analysis of the CHK1 signaling pathway showed that H1299 cells have an increased dependence on the CHK1 pathway in response to chemotherapy. There was no increased sensitization to radiation in H1299 versus H1993.Conclusions
CHK1 inhibition by AZD7762 preferentially sensitizes high CHK1 expressing cells, H1299, to anti-metabolite chemotherapy as compared with low CHK1 expressing H1993 cells. Thus, CHK1 inhibitors may improve the efficacy of standard lung cancer therapies, especially for those subgroups of tumors harboring higher expression levels of CHK1 protein. 相似文献89.
Background: Maltreated children experience a variety of adverse outcomes including substance use problems. Although previous research indicated that there may be distinct trajectories of substance use among these youth, studies have examined them as if they were a single homogeneous group. Objectives: The goals of this study were to explore substance use trajectories among child welfare-involved youth and to identify characteristics that distinguish substance use trajectories. Methods: Data from the National Survey of Child and Adolescent Well-Being (NSCAW II) were used. Multilevel latent growth mixture modeling (MLGMM) was performed using a subsample of 625 youth from ages 11–17 years investigated for maltreatment in 2008–2009. Measures included self-reported use of substance use during the previous 30 days, demographic characteristics, maltreatment history, placement in out-of-home care, and behavioral health problems. Results: MLGMM identified two distinct substance use trajectory classes including High Stable Substance Use and Rapid Progression Use. Findings suggest that the experience of physical abuse is the key factor that distinguishes the two groups. When the effects of class-specific covariates were examined, results suggest that involvement in substance use behavior and its escalation vary between groups and are affected by youth’s different previous experiences. Conclusions/Importance: The results have important implications for understanding individual differences in substance use behavior over time and how these differences were shaped by youth’s experiences of family adversity. Study findings may be helpful for developing and enhancing the effectiveness of interventions targeted at decreasing substance use behaviors in child welfare-involved youth. 相似文献
90.
Veedamali S. Subramanian Svetlana M. Nabokina Hamid M. Said 《Digestive diseases and sciences》2014,59(3):583-590