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Selected AbstractsImmunotherapy against metastatic renal cell carcinoma with mature dendritic cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007Akihiko Matsumoto Objective: We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC). Methods: Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-, treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-,, interleukin (IL)-1,, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging. Results: The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation. Conclusions: We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria. [source] Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trialJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2006Antonella Tosti Abstract Background, Clinical efficacy of topical corticosteroids in alopecia areata (AA) is still controversial. Positive clinical results have been obtained using ointments with occlusive dressing but this approach has a low patient compliance. Recently, a new topical formulation (thermophobic foam: Versafoam®) of clobetasol propionate 0.05% has been introduced on the market (Olux®, Mipharm, Milan, Italy) (CF). This formulation is easy to apply. After application to the skin the foam quickly evaporates without residues and it has a good patient compliance. In vitro studies have also shown that this formulation enhances the delivery of the active compound through the skin. Aim, To evaluate the efficacy, safety and tolerability of CF in the treatment of moderate to severe AA. Subjects and methods, Thirty-four patients with moderate to severe AA (eight men, mean age 40 ± 13 years) were enrolled in a randomized, double-blind, right-to-left, placebo-controlled, 24-week trial. Alopecia grading score (AGS) was calculated at baseline and after 12 and 24 weeks of treatment using a 0,5 score (0 = no alopecia; 5 = alopecia totalis). Clobetasol foam and the corresponding placebo foam (PF) were applied twice a day for 5 days/week for 12 weeks (phase 1) using an intrapatient design (right vs. left). From weeks 13 to 24 each enrolled patient continued only with the treatment (both on the right and left site) that was judged to have a greater efficacy than that on the contralateral side (phase 2). The primary outcome of the trial, evaluated on an intention-to-treat basis, was the hair regrowth rate, which was evaluated using a semiquantitative score (RGS) (from 0: no regrowth, to 4: regrowth of 75%). Results, At baseline the AGS was 4.1 (range: 2,5). Nine (26%) patients prematurely concluded the trial. At the end of phase 1, a greater hair regrowth was observed in 89% of the head sites treated with CF vs. 11% in the sites treated with PF. The RGS was 1.2 ± 1.6 in the CF-treated sites and 0.4 ± 0.8 in the PF-treated sites (P = 0.001). A RGS of 2 (hair regrowth of more than 25%) was observed in 42% CF-treated sites and in 13% of PF-treated sites (P = 0.027). In seven subjects (20%) a RGS of 3 to 4 (hair regrowth of 50%) was observed in CF-treated sites. In three subjects (9%) a RGS of 4 (hair regrowth of 75%) was observed in CF-treated sites. In one patient only, in a PF-treated region, a RGS of 3 was observed. The AS was reduced to 3.8 by CF treatment at the end of phase 1 and to 3.3 at the end of phase 2 (P = 0.01). From weeks 12 to 24 the treatment with CF induced a further increase in the RGS (from 1.2 to 1.5 ± 1.4). Forty-seven per cent of CF-treated patients had a RGS of 2 at the end of the trial. A total of eight patients (25%) at the end of the treatment with CF showed a RGS of 3. Folliculitis occurred in two patients. No significant modifications in cortisol and ACTH blood levels were observed during the trial. Conclusion, This new formulation of clobetasol propionate foam is an effective, safe and well-tolerated topical treatment for AA. This formulation has a good cosmetic acceptance and patient compliance profile. [source] Cross-reactivity among p -amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testingCONTACT DERMATITIS, Issue 2 2004P. Tornero We studied 28 patients with fixed drug eruption (FDE) caused by sulfonamide antibiotics to investigate cross-reactivity between sulfonamide derivatives and p -amino compounds and to explore the usefulness of patch testing, as an alternative to controlled oral challenge testing (COCT), in diagnosis within this clinical area. COCT with sulfamethoxazole (SMX), sulfadiazine (SDZ), sulfamethizole (SMZ), furosemide (FU), procaine (PRO) and glipizide (GPZ) was performed. Patch testing (PT) with SMX and SDZ was carried out. In all patients, the diagnosis of FDE was confirmed by positive COCT and allergy to trimethoprim ruled out by COCT. 42.8 and 31.8% of the SMX-induced FDE patients reacted to SMZ and SDZ, respectively. All patients (n = 28) tolerated FU, PRO and GPZ. COCT performed with the 3 sulfonamide antibiotics in 12 patients was positive in 2 subjects with the 3 drugs, in 2 patients only with SMX and SMZ and in the remaining 8, SMX was the only causative drug. PT was positive in 5 of 25 patients positive on COCT. The probability of obtaining a positive PT was higher among patients who had a residual lesion than that among those who lacked this. Cross-reactivity between different sulfonamide antibiotics is thus variable, being most likely between SMX and SMZ. We have found no cross-reactivity between sulfonamide antibiotics and other sulfonamide derivatives or p -amino drugs in FDE. PT is a useful tool in the diagnosis of FDE, especially if there are residual lesions, because it avoided the need for COCT in 20% of patients. [source] A randomized controlled study of paroxetine and cognitive-behavioural therapy for late-life panic disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010G.-J. Hendriks Hendriks G-J, Keijsers GPJ, Kampman M, Oude Voshaar RC, Verbraak MJPM, Broekman TG, Hoogduin CAL. A randomized controlled study of paroxetine and cognitive-behavioural therapy for late-life panic disorder. Objective:, To examine the effectiveness of paroxetine and cognitive-behavioural therapy (CBT) in elderly patients suffering from panic disorder with or without agoraphobia (PD(A)). Method:, Forty-nine patients aged 60+ years with confirmed PD(A) were randomly assigned to 40 mg paroxetine, individual CBT, or to a 14-week waiting list. Outcomes, with avoidance behaviour and agoraphobic cognitions being the primary measures, were assessed at baseline and at weeks 8, 14 (conclusion CBT/waiting list), and at week 26 (treated patients only) and analysed using mixed models. Results:, All outcome measures showed that the patients having received CBT and those treated with paroxetine had significantly better improvement compared with those in the waiting-list condition. With one patient (1/20, 5%) in the CBT and three (3/14, 17.6%) in the paroxetine condition dropping out, attrition rates were low. Conclusion:, Patients with late-life panic disorder respond well to both paroxetine and CBT. Although promising, the outcomes warrant replication in larger study groups. [source] One-Year Postoperative Autobiographical Memory Following Unilateral Temporal Lobectomy for Control of Intractable EpilepsyEPILEPSIA, Issue 3 2007Virginie Voltzenlogel Summary:,Purpose: To examine the effects of temporal lobectomy (TL), particularly concerning its lateralization. Methods: Patients completed autobiographical memory tests, preoperatively and 1-year postoperatively. Results: (a) right TL (RTL) patients recalled significantly more memories from the year after surgery than from the year before TL; (b) their pre to postoperative improvement on autobiographical memory scores was positively correlated to improvement of delayed story recall scores; and (c) 1 year after surgery, performance on recent personal memory recall was normalized for RTL patients only. Conclusion: We suggest that, in the absence of recurrent seizures, the relative integrity of the left hemisphere together with residual right hemisphere structures sustains postoperative autobiographical memory consolidation, at least 1 year postoperatively. [source] Association Between Migraine and Headache Attributed to Stroke: A Case,Control StudyHEADACHE, Issue 10 2008Katiuscia Nardi MD Background., Several studies were carried out to investigate the occurrence of headache attributed to acute stroke in patients with a lifetime history of migraine. Methods., In a case,control series of 96 acute stroke patients with a lifetime history of migraine (M+) and 96 stroke patients without (M,), ischemic stroke patients only, without secondary infarction, were selected. The headache attributed to acute ischemic stroke was then analyzed. Results., (M+) patients complained of headache more often than (M,) patients (P < .0001), mainly in the 24 hours before stroke onset (P < .0001). Migraine-like features of headache were recognized in a greater proportion of cases in the (M+) patient group with ischemic stroke (P < .018). A preferential brainstem location of ischemic stroke in (M+) patients emerged compared with (M,) patients (P = .014). Discussion., The high prevalence of headache attributed to stroke in (M+) patients, in a relevant proportion of cases presenting as a sentinel headache, suggests that cerebral ischemia lowers the threshold for head pain more easily in these "susceptible" patients. The most frequent involvement of the brainstem in (M+) patients with ischemic infarction concurs with recent reports that emphasized a greater headache frequency when cerebral infarctions are localized in this structure or deep brain gray matter. [source] The IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene-environment interactionINFLAMMATORY BOWEL DISEASES, Issue 1 2005Marie Pierik MD Abstract Background and Aims: The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis are complex disorders with an important genetic determinant. One gene associated with CD has been identified: NOD2/CARD15. Two independent genome-wide scans found significant evidence (logarithm of odds [LOD] 3.6) and suggestive evidence (LOD 2.8) for linkage on locus 14q11-12, also known as the IBD4 locus. To further characterize this locus, we assessed gene-environment interaction (IBD4 × smoking) and phenotypic heterogeneity in a large cohort of IBD-affected sibling pairs as part of an ongoing international collaborative effort. Patients and Methods: A total of 733 IBD families, comprising 892 affected sibling pairs, were genotyped for microsatellites D14S261, D14S283, D14S972, and D14S275, spanning the IBD4 locus. Information on gender, ethnicity, age at onset, smoking at diagnosis, extraintestinal manifestations, and disease location was available. Results: A significant distortion in the mean allele sharing (MAS) between affected siblings was observed for CD patients only at each of the four markers (54.6%, 52.8%, 50.4%, and 53.3%, respectively). Maximum linkage for CD was observed at marker D14S261 (multipoint nonparametric linkage score 2.36; P , 0.01; MAS 54.6%). MAS was higher in CD families in which all siblings or at least one sibling smoked compared with nonsmoking CD families (MAS, 58.90%, 57.50%, and 52.80%, respectively). Conclusions: The IBD International Genetics Consortium replicated the IBD4 locus on chromosome 14q for CD and also showed evidence for a gene-environment interaction at this locus. Further studies are needed to explore the mechanism by which smoking influences IBD4. [source] Screening for depression and anxiety: correlates of non-response and cohort attrition in the Netherlands Study of Depression and Anxiety (NESDA)INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 4 2009Willem Jan Van Der Veen Abstract A major problem in the analysis of attrition of cohorts in studies on mental health problems is that data on those who do not participate at the outset of a study are largely unavailable. It is not known how underlying psychopathology affects the first stages of screening where non-response and selectivity are usually highest. This article presents results of one of the centres of the Netherlands Study of Depression and Anxiety (NESDA), a longitudinal study aimed at describing the long-term course and consequences of depression and anxiety disorders. The aim is to describe the different ways of attrition during the first NESDA-wave in a cohort of patients aged 18,65 years of the Registration Network Groningen and to analyse whether attrition is related to gender, age and psychopathology as recorded in general practice. The attrition of the study cohort (n = 8475) was highest during the first stages, eventually leading to a population of 169 patients only who participated in the full NESDA-programme. Probabilities of transition from one stage of the screening process to the next were regressed on selected background variables using binary logistic regression. Correlates of participation were being female and being older (>40). Psychopathology was an important variable in the formation of the initial sample cohort, but only had a weak influence on patient response to the screening questionnaire. Study design factors had a stronger impact on the changing composition of the cohort at each screening stage compared to patient factors. Copyright © 2009 John Wiley & Sons, Ltd. [source] ,-thalassaemia carrier detection by ELISA: A simple screening strategy for developing countriesJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2005M. Shyla Ravindran Abstract The frequency of ,-thalassaemia in India ranges from 3.5% to 15% in the general population and of the 100,000 children born with thalassaemia major in the world, 10,000 are in India alone. Affected children do not die immediately, but treatment by regular transfusion is costly and leads to iron overload and death. Therefore, health services in lower-economic countries can sustain patients only if the numbers can be limited. Detecting carrier couples by simple blood test can prevent thalassaemia and at-risk couples can be identified and informed of their genetic risk before having children. A prevention programme including population screening, counselling, and prenatal diagnosis will markedly reduce the birth prevalence of affected individuals. Hemoglobin A2 (HbA2) measurement in human hemolysates has great significance, since its level can indicate ,-thalassaemia carrier status in otherwise healthy individuals. We have developed a rapid, simple, and inexpensive enzyme linked immunosorbent assay (ELISA) for the quantitation of HbA2, which can be used in carrier screening programmes in developing countries like India. In a limited trial for ,-thalassaemia carrier screening, the results obtained with ELISAs were compared with those obtained with the microcolumn chromatography method (r=0.89). J. Clin. Lab. Anal. 19:22,25, 2005. © 2005 Wiley-Liss, Inc. [source] Small bowel hydro-MR imaging for optimized ileocecal distension in Crohn's disease: Should an additional rectal enema filling be performed?JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2005Waleed Ajaj MD Abstract Purpose To assess the impact of an additional rectal enema filling in small bowel hydro-MRI in patients with Crohn's disease. Materials and Methods A total of 40 patients with known Crohn's disease were analyzed retrospectively: 20 patients only ingested an oral contrast agent (group A), the other 20 subjects obtained an additional rectal water enema (group B). For small bowel distension, a solution containing 0.2% locust bean gum (LBG) and 2.5% mannitol was used. In all patients, a breathhold contrast-enhanced T1w three-dimensional volumetric interpolated breathhold examination (VIBE) sequence was acquired. Comparative analysis was based on image quality and bowel distension as well as signal-to-noise ratio (SNR) measurements. MR findings were compared with those of conventional colonoscopy, as available (N = 25). Results The terminal ileum and rectum showed a significantly higher distension following the rectal administration of water. Furthermore, fewer artifacts were seen within group B. This resulted in a higher reader confidence for the diagnosis of bowel disease, not only in the colon, but also in the ileocecal region. Diagnostic accuracy in diagnosing inflammation of the terminal ileum was 100% in group B; in the nonenema group there were three false-negative diagnoses of terminal ileitis. Conclusion Our data show that the additional administration of a rectal enema is useful in small bowel MRI for the visualization of the terminal ileum. The additional time needed for the enema administration was minimal, and small and large bowel pathologies could be diagnosed with high accuracy. Thus, we suggest that a rectal enema in small bowel MR imaging be considered. J. Magn. Reson. Imaging 2005;22:92,100. © 2005 Wiley-Liss, Inc. [source] Dihydropyrimidine dehydrogenases and cytidine-deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2008Juan J. Grau MD Abstract Background and Objectives Single nucleotide polymorphisms of dihydropyrimidine dehydrogenases gene (DPYD) induces dihydropyrimidine dehydrogenase enzyme (DPD) deficiency resulting in increased activity of 5-fluorouracil derivatives. Cytidine-deaminase gene (CDA) polymorphisms have been involved in prognosis in experimental tumours. Methods Analysis of 50 consecutive resected gastric cancer patients who received adjuvant chemotherapy with Tegafur for polymorphisms of genes DPYD1 (A/G; Ile543Val), DPYD2 (C/T; Arg29Cys) and CDA (A/C; Lys27Gin). The status of alleles (wild-type or at least one polymorphism) was correlated with outcome and toxicity. Results Polymorphisms frequencies wild-type/non-wild-type were 36/14 in DPYD1 (A/G; Ile543Val); 26/24 in DPYD2 (C/T; Arg29Cys); and 17/23 in CDA (A/C; Lys27Gin) or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow-up (SD,=,26.3), 18 patients died of tumour relapse. Better survival was observed in DPYD1 patients only, for non-wild-type over wild-type (P,=,0.0214); and in patients with one or more heterozygous polymorphisms in any of the three genes tested (P,=,0.0017). In 10 pts (20%) total dose was reduced by toxicity, only 3 of them were homozygous. Conclusions Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy. J. Surg. Oncol. 2008;98:130,134. © 2008 Wiley-Liss, Inc. [source] UVB in the management of early stage mycosis fungoidesJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2006F Pavlotsky Background, Several options for treatment of early mycosis fungoides (MF) offer similar success rates. Previous small studies have shown UVB to be at least as effective as PUVA. Objective, To summarize our experience with UVB treatment of early MF. Methods, A retrospective analysis of early-stage MF patients treated by narrow band (NB) or broad band (BB) UVB in our institution between 1996 and 2002. Most patients achieving complete response (CR) were put on maintenance until natural sun exposure was possible and followed up every 3,6 months. The results were compared to those previously reported regarding PUVA. Results, Sixty-eight and 43 patients were treated by NB and BB UVB, respectively. Eighty-six per cent (84 and 89% in NB and BB UVB groups, respectively) of IA and 71% (78 and 44% in NB and BB UVB groups, respectively) of IB patients achieved CR within a mean of 12.8 and 10.6 weeks, respectively. When maintenance was stopped, 65 and 30% had not relapsed after an average follow up of 27 and 222 weeks, respectively. Non-relapse rate was 33 and 48% for those having had vs. those not having had maintenance, respectively. Conclusions, Our results are comparable to all previously reported for skin-targeted treatments, including PUVA and, to our belief, reflect the nature of early MF, in which CR can probably be achieved in most of the patients. Among the responding patients there is no relapse during prolonged follow-up in about one third of the cases. Thus, we believe treatment should be stopped completely following first CR induction and maintenance treatment should be considered for relapsing patients only. Both broad and narrow UVB options are good and future choices should be made on the basis of short- and long-term side-effects. [source] Influence of HFE gene polymorphism on the progression and treatment of chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 2 2004P. Lebray Summary., We analysed liver histology findings in a large cohort of patients with chronic hepatitis C and in roughly half of them their response to interferon- , -based on iron parameters and HFE status. Histological activity and virological response to antiviral therapy (n = 146) were analysed in 273 immunocompetent and nonalcoholic patients with chronic hepatitis C, in terms of serum iron load, intrahepatic iron load (n = 110) and HFE mutations. Patients who were heterozygous for the C282Y and H63D mutations exhibited higher iron serum parameters than subjects without these mutations. The intrahepatic iron load was higher in H63D patients only. No association was observed between HFE mutations and histological activity. Increased iron parameters were associated with liver disease severity by univariate analysis only. Genotype 1 and ferritinaemia were associated with a poor response to antiviral therapy, whereas the H63D mutation emerged as a positive predictive factor for end of treatment and sustained antiviral response. Therefore, in chronic hepatitis C patients serum and intrahepatic iron levels were weakly correlated with histological activity, while HFE mutations were not. As for the response to interferon- ,, elevated ferritinaemia constituted a negative predictive factor whereas the H63D mutation was a positive one. The H63D mutation might form part of an immunogenetic profile influencing the response to interferon therapy. [source] Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patientsLIVER TRANSPLANTATION, Issue 4 2007Edie Y. Chan Acute cellular graft-vs.-host disease (GVHD) following liver transplantation has an incidence of 1 to 2% and a mortality rate of 85%. Our aim was to identify a patient population at high risk for developing GVHD using a large clinical database to study both recipient and donor factors. We compared our liver transplant patients who developed GVHD to those that did not for recipient and donor factors and combinations of factors. For 2003,2004 we had 205 first-time liver transplant patients surviving >30 days. From this group, 4 (1.9%) developed GVHD. Compared to the control group, there were no significant differences in recipient age, recipient gender, donor age, donor gender, total ischemia time, donor-recipient human leukocyte antigen (HLA) mismatch, or donor-recipient age difference. Percentages of liver disease etiologies among the patients who developed GVHD were as follows: 16% (1/6) autoimmune hepatitis (AIH) (P = 0.003), 5.6% (3/54) alcoholic liver disease (ALD) (P = 0.057), and 7.1% (3/42) hepatocellular carcinoma (HCC) (P = 0.026). The incidence of GVHD in patients with glucose intolerance (either Type I or Type II diabetes mellitus [DM]) was significant (P = 0.022). Focusing on patients only with high-risk factors for GVHD during the years 2003,2005, we had 19 such patients. Four of these high-risk patients developed GVHD. Three of these 4 patients had received a donor liver with steatosis of degree ,mild compared to only 2 of the 15 high-risk patients who did not develop GVHD (P = 0.037). In conclusion, we have identified liver transplant patients with AIH or the combination of ALD, HCC, and glucose intolerance who receive a steatotic donor liver as being at high risk for developing GVHD. Liver Transpl 13:516,522, 2007. © 2007 AASLD. [source] Real-time single-heartbeat fast strain-encoded imaging of right ventricular regional function: Normal versus chronic pulmonary hypertension,MAGNETIC RESONANCE IN MEDICINE, Issue 1 2010Monda L. Shehata Abstract Patients with pulmonary hypertension and suspected right ventricular (RV) dysfunction often have dyspnea at rest, making reliable assessment of RV function using traditional breath-holding methods difficult to perform. Using single-heartbeat fast strain encoding (Fast-SENC) imaging, peak systolic RV circumferential and longitudinal strains were measured in 11 healthy volunteers and 11 pulmonary hypertension patients. Fast-SENC RV longitudinal strain and circumferential strain measurements were compared to conventional SENC and MR tagging, respectively. Fast-SENC circumferential and longitudinal RV shortening correlated closely with SENC measurements (r = 0.86, r = 0.90, P < 0.001 for all). Circumferential strain, by conventional tagging, showed moderate correlation with Fast-SENC in pulmonary hypertension patients only (r = 0.5, P = 0.003). A nonuniform pattern of RV circumferential shortening was depicted in both groups. Peak systolic circumferential strain was significantly reduced at the basal RV in pulmonary hypertension patients (,18.06 ± 3.3 versus ,21.9 ± 1.9, P < 0.01) compared to normal individuals, while peak systolic longitudinal strain was significantly reduced at all levels (P < 0.01 for all). Fast-SENC is a feasible and reliable technique for rapid quantification of RV regional function in a single-heartbeat acquisition. Information derived from Fast-SENC allows characterization of RV regional function in normal individuals and in pulmonary hypertension patients. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [source] Mechanical strain increases cytokine and chemokine production in bronchial fibroblasts from asthmatic patientsALLERGY, Issue 1 2009F. Le Bellego Background:, Mechanical strain and cytokine stimulation are two important mechanisms leading to airway remodeling in asthma. The effect of mechanical strain on cytokine secretion in airway fibroblasts is not known. The aim of this study was to determine whether bronchial and nasal fibroblasts differentially alter cytokine secretion in response to mechanical strain. Methods:, We measured secretion of the pro-fibrotic cytokine, interleukin-6 (IL-6), and the pro-inflammatory cytokines, IL-8 and monocyte chemotactic protein 1, before and after mechanical strain in bronchial fibroblasts obtained from asthmatic patients [asthmatic bronchial fibroblasts (BAF)] and normal volunteers [normal bronchial fibroblasts (BNF)], and in nasal fibroblasts (NF) obtained from nasal polyps. Cells were grown on flexible membranes and a mechanical strain of 30% amplitude, 1 Hz frequency was applied for 3, 6 and 24 h. Control cells were unstrained. IL-6, IL-8 and monocyte chemotactic protein 1 was measured after 24 h strain using enzyme-linked immunoassay; mRNA was measured by real time polymerase chain reaction. We also measured mRNA for versican, a matrix proteoglycan, known to be upregulated in the asthmatic airway wall. Results:, In unstrained conditions, no differences in cytokine secretion were observed. After 24 h strain, BAF secreted more IL-6 than BNF. Mechanical strain increased IL-8 mRNA in BAF, BNF and NF; and IL-6 and versican mRNA, in BAF, only. Conclusions:, Cytokine responses to mechanical strain varied in different airway fibroblast populations, and depended on the site of origin, and the underlying inflammatory state. Strain resulted in IL-6 upregulation and increased message for extracellular matrix protein in bronchial fibroblasts from asthmatic patients only, and may reflect these patients' propensity for airway remodeling. [source] Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using 1H and 31P magic angle spinning MRS of intact tissueNMR IN BIOMEDICINE, Issue 2 2009Sonali S. De Silva Abstract The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n,=,5), cervical intraepithelial neoplasia (CIN; mild, n,=,5; moderate/severe, n,=,40), and invasive cancer (n,=,23). 1H HR-MAS MRS data were acquired using a Bruker Avance 11.74,T spectrometer (Carr,Purcell,Meiboom,Gill sequence; TR,=,4.8,s; TE,=,135,ms; 512 scans; 41,min acquisition). 31P HR-MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a 1H-decoupled pulse-acquire sequence (TR,=,2.82,s; 2048 scans; 96,min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P,=,0.0001) and phosphocholine (P,=,0.002) in tissue from patients with cancer than from patients with high-grade dyskaryosis, but no differences between non-cancer groups. Division by histology of the sample also showed increases in choline (P,=,0.002) and phosphocholine (P,=,0.002) in cancer compared with high-grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P,=,0.0001). Estimated concentrations of alanine (P,=,0.01) and creatine (P,=,0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non-cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non-cancer patients (P,=,0.0001). Estimated concentrations of choline-containing metabolites increased from pre-invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue. Copyright © 2008 John Wiley & Sons, Ltd. [source] Safety and Acceptability of Implantation of Internal Cardioverter-Defibrillators Under Local Anesthetic and Conscious SedationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2007DAVID J. FOX B.M.Sc., M.B.Ch.B., M.R.C.P. Background: Implantation and testing of implantable defibrillators (ICDs) using local anesthetic and conscious sedation is widely practiced; however, some centers still use general anesthesia. We assessed safety and patient acceptability for implantation of defibrillators using local anesthetic and conscious sedation. Methods: The records of 500 consecutive device implants from two UK cardiac centers implanted under local anesthetic and conscious sedation from January 1996 to December 2004 were reviewed. Procedure time, left ventricular ejection fraction (LVEF) sedative dosage (midazolam), analgesic dosage (fentanyl or diamorphine), requirement for drug reversal, and respiratory support were recorded. Patient acceptability of the procedure was also assessed. Results: Of 500 implants examined, 387 were ICDs, 88 were biventricular ICDs, and 25 were generator changes. Patients with biventricular-ICDs had significantly longer (mean ± SD) procedure times 129.7 ± 7.6 minutes versus 63.3 ± 32.3 minutes; P < 0.0001 and lower LVEF 24.4 ± 8.4% versus 35.7 ± 15.4%; P < 0.0001. There were no differences in the doses (mean ± SD) of midazolam 8.9 ± 3.5 mg versus 8.0 ± 3.1 mg; P = NS, diamorphine 4.3 ± 2.0 mg versus 3.8 ± 1.7 mg; P = NS or fentanyl 94.4 ± 53.7 mcg versus 92.2 ± 48.6 mcg; P = NS, between the two groups. There were no deaths or tracheal intubations in either group. Acceptability was available for 373 of 500 (75%) patients, 41 of 373 (11%) described "discomfort," but from these 41 patients only 14 of 373 (3.8%) declined a second procedure under the same conditions. Conclusions: Implantation of defibrillators under local anesthetic and sedation is safe and acceptable to patients. General anesthesia is no longer routinely required for implantation of defibrillators. [source] Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: A children's oncology group study,,PEDIATRIC BLOOD & CANCER, Issue 4 2010MRCP, Rani E. George MD Abstract Background Demethylating agents may alter the expression of genes involved in chemotherapy resistance. We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors. Procedure Stratum A included children with any solid tumor; Stratum B included neuroblastoma patients only. Patients received a 1-hr decitabine infusion for 7 days, followed by doxorubicin (45,mg/m2) and cyclophosphamide (1,g/m2) on day 7. Pharmacokinetic studies were performed after the first dose of decitabine. Biological studies included methylation and gene expression analyses of caspase-8, MAGE-1 and fetal hemoglobin (HbF), and expression profiling of pre- and post-treatment peripheral blood and bone marrow cells. Results The maximum-tolerated dose of decitabine was 5,mg/m2/day for 7 days. Dose-limiting toxicities at 10,mg/m2/day were neutropenia and thrombocytopenia. Decitabine exhibited rapid clearance from plasma. Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for ,4 months. Sustained MAGE-1 demethylation and increased HbF expression were observed in the majority of patients post-treatment (12/20 and 14/16, respectively). Caspase-8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples. Differentially expressed genes were identified by microarray analysis. Conclusion Low-dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children. However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination. Alternative strategies of combining demethylating agents with non-cytotoxic, biologically targeted agents such as histone deactelyase inhibitors should be explored. Pediatr Blood Cancer. 2010;55:629,638. © 2010 Wiley-Liss, Inc. [source] Sequence of cardiovascular changes in IUGR in pregnancies with and without preeclampsiaPRENATAL DIAGNOSIS, Issue 5 2008Giancarlo Mari Abstract Objective The aim of this study was to determine the cardiovascular changes sequence in intrauterine-growth-restricted (IUGR) fetuses using Doppler ultrasound. Methods Sequential Doppler evaluations were carried out in 29 severe IUGR fetuses in pregnancies without maternal medical complications (group A) and in pregnancies complicated by preeclampsia (group B) delivered at , 32 weeks. Nine fetal vessels and two cardiac valves were studied. Results One hundred and forty three Doppler studies were performed (median: five studies; range 3,9 per patient). There were 19 fetuses in the preeclamptic group and 10 fetuses in the second group. In group A IUGR fetuses, a progressive change was observed in the parameters studied more often than in group B IUGR fetuses (P < 0.05). In six cases, an abnormal tricuspid valve (TV) followed by an abnormal mitral valve (MV) Doppler was recorded prior to the occurrence of the intrauterine-fetal demise. Conclusions Our data indicate that (1) in patients without preeclampsia a series of cardiovascular changes almost always occurs in severe IUGR fetuses; (2) the changes preceding intrauterine demise are right cardiac failure followed by left cardiac failure; (3) in patients with preeclampsia, the sequential Doppler changes are unpredictable and are seen in a few patients only. Copyright © 2008 John Wiley & Sons, Ltd. [source] Improving Outcomes of Liver Retransplantation: An Analysis of Trends and the Impact of Hepatitis C InfectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008M. Ghabril Retransplantation (RT) in Hepatitis C (HCV) patients remains controversial. Aims: To study trends in RT and evaluate the impact of HCV status in the context of a comprehensive recipient and donor risk assessment. The UNOS database between 1994 and October 2005 was utilized to analyze 46 982 LT and RT. Graft and patient survival along with patient and donor characteristics were compared for 2283 RT performed in HCV and non-HCV patients during 1994,1997, 1998,2001 and 2002,October 2005. Overall HCV prevalence at RT increased from 36% in the initial period to 40.6% after 2002. In our study group, 1-year patient and graft survival post-RT improved over the same time intervals from 65.0% to 70.7% and 54.87% to 65.8%, respectively. HCV was only associated with decreased patient and graft survival with a retransplant (LT-RT) interval (RI) >90 days. Independent predictors of mortality for RT with RI >90 days were patient age, MELD score >25, RI <1 year, warm ischemia time ,75 min and donor age ,60 (significant for HCV patients only). Outcomes of RT are improving, but can be optimized by weighing recipient factors, anticipation of operative factors and donor selection. [source] Use of octreotide and lanreotide in the treatment of symptomatic non-resectable carcinoid tumoursANZ JOURNAL OF SURGERY, Issue 9 2002Muhammad Rohaizak Background: Carcinoid tumours are rare neoplasms that secrete hormones and biogenic amines, most commonly serotonin. Octreotide and long acting lanreotide are found to be useful in the management of carcinoid syndrome by its interaction with somatostatin receptor, found on the carcinoid tumour. The aim of this study is to look at the efficacy of octreotide and long acting lanreotide in the treatment of symptomatic non-resectable carcinoid tumours. Method: The effects of octreotide and long-acting lanreotide were studied in 10 patients with symptomatic non-resectable carcinoid tumours. Results: Symptom improvement occurred in nine of 10 patients. Three patients responded only to octreotide, three patients responded to both octreotide and long-acting lanreotide and three patients only responded to long-acting lanreotide. Slight reductions in 24-h urine 5-hydroxyindoleacetic acid levels occurred in three of six patients but no patients were found to have objective tumour regression on computed tomography scan. Conclusions: Octreotide and long-acting lanreotide are useful palliative treatments for the control of symptoms in patients with non-resectable carcinoid tumours but there is no evidence of tumour stasis. [source] Enucleation of renal cell carcinoma with ablation of the tumour baseBJU INTERNATIONAL, Issue 6 2008Alexander Kutikov OBJECTIVE To retrospectively assess the effectiveness of cancer control with enucleation of renal cell carcinoma (RCC), which is surgically expedient, allows preservation of maximal renal parenchyma, and makes intraoperative renal ischaemia unnecessary, by two surgeons routinely enucleating renal tumours and ablating the tumour bed with argon beam and the Nd-YAG laser. PATIENTS AND METHODS Between 1996 and 2006 at our institution, 97 patients had RCC enucleated, with ablation of the tumour base. Patients with lesions other than RCC and those with von Hippel-Lindau disease or Birt-Hogg-Dube syndrome were excluded from the study. The mean follow-up was 24.9 months. Patients were evaluated for RCC recurrence with cross-sectional imaging at least every 6 months for the first 2 years and then annually thereafter. RESULTS The mean (median, range) tumour size was 2.8 (2.5, 0.8,7.0) cm. Of the 97 patients only one had disease progression after a mean follow-up of 24.9 months. This patient presented with a solitary grade 2 clear cell RCC and had a local recurrence 30 months after original surgery. CONCLUSIONS The present series and other available clinical data suggest that enucleation with cavity ablation is an oncologically sound approach that is simple, versatile and obviates the need for renal ischaemia. [source] The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescenceBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005Birgit Burkhardt Summary We analysed the impact of age and gender on biology and outcome of 2084 patients diagnosed with non-Hodgkin lymphoma (NHL) between October 1986 and December 2002 and treated according to the Berlin-Frankfurt-Münster (BFM) multicentre protocols NHL-BFM-86, -90 and -95. Median age at diagnosis was 8·0 years for 97 precursor B-lymphoblastic lymphoma (pB-LBL) patients, 8·8 years for 335 T-lymphoblastic lymphoma (T-LBL) patients, 8·4 years for 1004 Burkitt's lymphoma/leukaemia (BL/B-AL) patients, 11·4 years for 173 diffuse large B-cell lymphoma (centroblastic subtype) (DLBCL-CB) patients, 13·2 years for 40 primary mediastinal large B-cell lymphoma (PMLBL) patients and 10·8 years for 215 anaplastic large-cell lymphoma (ALCL) patients (P < 0·00001). The male:female ratio was 0·9:1 for pB-LBL and PMLBL, 1·7:1 for DLBCL-CB, 1·8:1 for ALCL, 2·5:1 for T-LBL and 4·5:1 for BL/B-AL (P < 0·00001). The probability of event-free survival at 5 years (5-year pEFS) was 85 ± 1% for all 2084 patients [median follow-up 5·7 (0·1,15·9) years], and was significantly superior for male T-LBL and DLBCL-CB patients. Comparing age-groups 0,4, 5,9, 10,14 and 15,18 years, pEFS was inferior for the youngest patients only in the pB-LBL- and ALCL-groups. T-LBL and DLBCL-CB adolescent females had worse outcome than younger girls while age had no impact on pEFS for boys. We conclude that the distribution of age and gender differed between NHL-subtypes. The impact of gender on outcome differed between NHL subgroups. The prognostic impact of age differed not only by NHL-subtype but also according to gender in some subtypes. [source] Intravitreal bevacizumab (Avastin) as a treatment of the neovascular complications of laser-induced chorioretinal anastomosis for nonischaemic central retinal vein occlusionCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 5 2009Kenneth C S Fong FRCOphth Abstract Purpose:, To describe the use of intravitreal bevacizumab followed by sectorial retinal photocoagulation to treat the neovascular complications of laser-induced chorioretinal anastomosis (L-CRA) for nonischaemic central retinal vein occlusion (CRVO). Methods:, Prospective interventional case series of three patients with nonischaemic CRVO who were treated with L-CRA. Patients were followed up every 2 weeks after the laser treatment. If neovascularization occurred at the site of the anastomosis, intravitreal bevacizumab (1.25 mg) was injected followed by laser photocoagulation to areas of retinal ischaemia and the area of retina anterior to the L-CRA 1 week later. Fluorescein angiography was performed to confirm the presence of neovascularization. Best-corrected visual acuity measurements were performed at every visit. Results:, Three patients (one woman, two men) with a mean age of 76.3 years developed neovascularization at the L-CRA site and underwent treatment as described with a mean follow-up time of 7 months. The neovascularization developed within 1 month after the laser anastomosis in all three cases. All patients only required one intravitreal bevacizumab injection to control the neovascularization. No complications of the intravitreal injections were noted. Conclusions:, Intravitreal bevacizumab appears to be an effective tool in the immediate control of neovascularization following L-CRA for nonischaemic CRVO. This appears to cause immediate regression of the neovascular frond and allows time for the laser, which is applied subsequently to have its effect. [source] | |||||||||||||||||||||||||