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Kinds of Treatment. Selected AbstractsEpidural Neurostimulation of Posterior Funiculi for the Treatment of Buerger's DiseaseNEUROMODULATION, Issue 2 2009Lorena Vaquer Quiles ABSTRACT Background., Buerger disease is a nonatherosclerotic, segmental, occlusive and recurrent inflammatory vascular disorder that affects small and medium-sized arteries and veins of the upper and lower extremities. Case reports., We report two cases of Buerger disease. Medical History., Smoking habit. No autoimmune diseases. No diabetes mellitus. Intermittent vascular claudication at 100,150 m. Several hospital admissions for amputations. Prior Medical Treatment., Antiplatelet agents, vasodilators, nonsteroidal anti-inflammatory drugs, third-step analgesics, fibrinolytic treatment and lumbar sympathectomies. Following all of the above treatments, Synergy®spinal cord (ECP) stimulator with two electrodes (Quad PISCES©) placed at the level of T9,T10. Results., There has been a reduction in pain of about 80% and an improvement of intermittent claudication (one of the patients no longer claudicates, whereas the other patient claudicates at 400 m). Conclusion., Neurostimulation of the posterior funiculi could be considered not only as palliative care but also as a therapeutic option. [source] Growth, etching morphology and spectra of LiAlO2 crystalCRYSTAL RESEARCH AND TECHNOLOGY, Issue 8 2008Taohua Huang Abstract ,-LiAlO2 single crystal was successfully grown by Czochralski method. The crystal quality was characterized by X-ray rocking curve and chemical etching. The effects of air-annealing and vapor transport equilibration (VTE) on the crystal quality, etch pits and absorption spectra of LiAlO2 were also investigated in detail. The results show that the as-grown crystal has very high quality with the full width at half maximum (FWHM) of 17.7-22.6 arcsec. Dislocation density in the middle part of the crystal is as low as about 3.0×103 cm,2. The VTE-treated slice has larger FWHM value, etch pits density and absorption coefficient as compared with those of untreated and air-annealed slices, which indicates that the crystal quality became inferior after VTE treatment. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] CD203c-based basophil activation test in allergy diagnosis: Characteristics and differences to CD63 upregulation,CYTOMETRY, Issue 5 2010Eva M. Sturm Abstract Background: The basophil activation test (BAT) based on CD203c upregulation has been validated as a reliable tool for the diagnosis of IgE-mediated allergies. Nevertheless, CD203c-based BAT is hardly comparable with that of CD63-based tests, as the mechanisms of CD203c versus CD63 induction differ considerably. The aim of the present study was to identify potent influencing factors of the CD203c-based BAT and to emphasize differences between CD63 and CD203c detection. Methods: CD203c-based BAT was determined in 82 healthy controls and in 79 allergic patients. The effects of interleukin (IL)-3 and degranulation enhancing substances were investigated and compared with CD63 upregulation. Furthermore, the influence of different storage conditions and incubation times was evaluated and the impact of antiallergic drugs on the test results was assessed. Results: CD203c and CD63 expression was rapidly upregulated reaching a maximum after 20,30 min. Basophil CD203c upregulation assayed after storage times up to 48 h declined already after 4 h. IL-3 treatment increased CD203c and CD63 baseline levels and decreased basophil CD203c responses in a dose-dependent manner. In contrast, cytochalasin B and latrunculin B did not affect CD203c responses but decreased CD63-based BAT. Finally, therapeutic concentrations of dimetindene and desloratadine did not affect CD203c upregulation. Conclusion: CD203c-based basophil activation test should be performed preferentially within 4 h after taking the blood samples. Priming and degranulation-enhancing factors are not required for CD203c-based BAT. In contrast to skin testing, CD203c-based BAT can be performed in patients undergoing antiallergic treatment. © 2010 International Clinical Cytometry Society [source] Improved methods for carbon adsorption studies for water and wastewater treatmentENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY, Issue 2 2006Wei-chi Ying Abstract An improved method was developed to rank activated carbon in removing organic water pollutants. The simple and standardized evaluation method uses a set of four adsorptive capacity indicators: phenol, iodine, methylene blue, and tannic acid numbers; those four indicator compounds were selected because they cover the molecular size range of most organic water pollutants. An improved microcolumn rapid breakthrough (MCRB) test method was developed from the existing HPMC (high-pressure minicolumn) and RSSCT (rapid small-scale column test) methods by simplifying the experimental procedure and using readily available low-cost pump, sampler, piping, and fittings. This method can be practiced in an ordinary environmental laboratory to select the best carbon, to verify the treatment effectiveness, and to estimate the adsorption treatment cost based on the observed capacity utilization rate for carbon in the adsorber without the problems often encountered with using small and mini traditional columns. The benefits of the four-parameter carbon selection method and the MCRB method were demonstrated by adsorption isotherm and breakthrough data for several indicator compounds and organic water pollutants. These improved methods will enable efficient carbon adsorption studies necessary for more applications of carbon adsorption technology in water and wastewater treatment. © 2006 American Institute of Chemical Engineers Environ Prog, 2006 [source] Vulvar Pain: A Phenomenological Study of Couples in Search of Effective Diagnosis and TreatmentFAMILY PROCESS, Issue 2 2008JENNIFER J. CONNOR PH.D. Vulvar vestibulitis syndrome (VVS), a vulvar pain disorder, continues to puzzle medical and mental health professionals due to its unknown etiology and lack of effective treatment. This study used transcendental phenomenology methodology to explore the experiences of couples in which the woman has a diagnosis of VVS. Sixteen in-depth semi-structured interviews were conducted with 13 heterosexual couples and 3 women. Four essences emerged: (1) In search of, the medical journey required extensive searching for knowledgeable and respectful practitioners to provide treatment. (2) The process of developing a personal understanding of this disorder led many couples to question their role in causing and maintaining VVS. (3) Developing strategies for coping with painful intercourse led to three strategies: becoming non-sexual, using alternatives to vaginal sex, and altering or enduring painful intercourse. (4) Feelings of isolation were experienced as adapting to this chronic pain syndrome was often a lonely process. Clinical suggestions included: treating the couple, not just the woman with VVS; encouraging couples to broaden definitions about the importance and primacy of vaginal intercourse and suggest alternative sexual activities less likely to cause vulvar pain; developing shared meaning as a couple, and assisting couples in locating physicians and resources. Suggestions are relevant for couples with VVS and those with chronic health problems affecting sexual relationships. RESUMEN Dolor vulvar: estudio fenomenológico de parejas que buscan un diagnóstico y tratamiento efectivos El síndrome de vestibulitis vulvar (svv), un trastono de dolor vulvar, continúa dejando perplejos a los profesionales de la salud física y mental debido a su etiología desconocida y a la inexistencia de un tratamiento efectivo. Este estudio utilizó metodología fenomenológica experimental para explorar las experiencias de parejas en que a la mujer se le ha diagnosticado el svv. Se llevaron a cabo dieciséis entrevistas (en profundidad y semiestructuradas) con 13 parejas heterosexuales y 3 mujeres, de las que se obtuvieron cuatro conclusiones esenciales: (1) En busca de , la investigación médica requería una búsqueda más exhaustiva de médicos eruditos y respetuosos que aportasen un tratamiento. (2) El proceso de desarrollar una comprensión personal del trastorno condujo a varias parejas a plantearse su papel en la causa y la prolongación del svv. (3) Desarrollar estrategias para afrontar un coito doloroso condujo a tres estrategias: prescindir del sexo, optar por alternativas al sexo vaginal y modificar o soportar el coito doloroso. (4) Se experimentaron sensaciones de aislamiento, pues el proceso de adaptación a este síndrome de dolor crónico resultó, a menudo, un proceso solitario. Entre los consejos clínicos se incluyen tratar a la pareja, y no sólo a la mujer con svv; animar a las parejas a ampliar las definiciones de la importancia y preferencia por el coito vaginal, así como sugerir actividades sexuales con menor riesgo de causar dolor vulvar; desarrollar un significado común como pareja; y ayudar a las parejas a encontrar médicos y recursos. Palabras clave: síndrome de vestibulitis vulvar; dolor vulvar; terapia de pareja. [source] Efficacy of diagnostic upper node evaluation during (salvage) laryngectomy for supraglottic carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2009Ronald J. E. Pennings MD Abstract Background. The effectiveness of selective upper node dissection or inspection during laryngectomy for supraglottic squamous cell carcinoma was evaluated. These diagnostic procedures aimed to cause less morbidity than elective neck dissection in patients with a clinically N0 neck. Methods. In 93 patients, 166 clinically N0 necks (73 bilateral and 20 contralateral) were evaluated. Lymph nodes at levels II and III were inspected or dissected and directly sent in for frozen section histopathology. This way, occult neck metastases were identified and treated by neck dissection. Results. Occult neck metastases were identified in 19% of the examined necks (31/166). Regional recurrence rate in the postoperative N0 necks was 0%, and 10% in the postoperative N+ necks. Conclusions. Selective upper node dissection and inspection during laryngectomy reduced the need for an elective neck dissection with its morbidity in the clinically N0 neck. In addition, it selects the patients who need such extensive treatment. © 2008 Wiley Periodicals, Inc. Head Neck, 2009. [source] Mycobacterium fortuitum,induced persistent parotitis: Successful therapy with clarithromycin and ciprofloxacinHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2007Chien-Cheng Chen MD Abstract Background. Parotitis caused by nontuberculous mycobacteria, a very rare disease entity, has never been reported to be caused by Mycobacterium fortuitum (M. fortuitum) in the literature. Methods and Results. An 8-year-old girl was seen with painful swelling of the right parotid gland despite antibiotic treatment of more than 1 month. Elevated serum amylase activity and diffuse contrast-enhanced CT of the parotid gland confirmed the diagnosis of parotitis. Histopathological study of specimens taken from the right parotid tail mass showed granulomatous inflammation with acid-fast positive bacilli; culture later confirmed M. fortuitum. After administration of clarithromycin and ciprofloxacin for 9 consecutive months, the parotitis and parotid tail mass were completely resolved at follow-up examination. Conclusion. To our knowledge, this is the first case report of parotitis caused by M. fortuitum and its successful medical treatment. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Complete hypopharyngeal obstruction by mucosal adhesions: A complication of intensive chemoradiation for advanced head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2006Elizabeth J. Franzmann MD Abstract Background. Severe swallowing dysfunction is the dominant long-term complication observed in patients treated for head and neck squamous cell carcinoma (HNSCC) with treatment protocols using intensive concurrent chemotherapy with radiation therapy (chemo/XRT). We identified a subset of these patients, who were seen with complete obstruction of the hypopharynx distal to the site of the primary cancer, and in whom we postulate that the obstruction was caused by separable mucosal adhesions rather than obliteration by a mature fibrous stricture. Methods. Seven patients were referred to the senior author with a diagnosis of complete hypopharyngeal obstruction between 1992 and 2001. The diagnosis was confirmed by barium swallow imaging and/or endoscopy before referral in all patients. Patients underwent recanalization by passing a Jesberg esophagoscope under general anesthesia, followed by serial dilations and intensive swallowing therapy. Patient charts were reviewed retrospectively after institutional review board approval. Results. All seven patients were successfully recanalized. No patient had a perforation or other significant complication related to the recanalization procedure or subsequent dilations. Five of the seven patients showed improvement in swallowing at some point after the initial procedure, but just two patients recovered sufficiently to have their gastrostomy tube removed permanently. Conclusions. We conclude that complete hypopharyngeal obstruction secondary to mucosal adhesions is one cause of gastrostomy tube dependence in patients who have been treated with chemo/XRT for HNSCC. It is a difficult problem to treat, but most patients can recover useful swallowing function without undergoing laryngectomy or major surgical reconstruction. The postulated pathophysiology has implications for prevention as well as treatment. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Treatment of early stage squamous-cell carcinoma of the glottic larynx: Endoscopic surgery or cricohyoidoepiglottopexy versus radiotherapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2001Lue P. Bron MD Abstract Background Both surgery and radiotherapy are recognized treatments of T1-T2 squamous cell carcinoma of the larynx. We retrospectively analyze and compare the oncological outcome of patients treated in a single institution, either by endoscopic surgery or partial supracricoid laryngectomy versus radiation therapy. Methods The medical records of 156 patients treated between 1983 and 1996 with either surgery (n = 75) or radiotherapy (n = 81) were reviewed. Male to female ratio, median age, and T-stage distribution were comparable. Results With a median follow-up time of 59 months, the 5-year cause-specific survival rate of 93% was identical for both groups. The actuarial incidence of metachronous second primaries was 7% at 5 years. Local control at 5 years remained 84% after surgery and 77% after radiotherapy. Anterior commissure infiltration was shown to represent a negative predictive factor of local control for radiotherapy (p = .01). Salvage treatment brought ultimate local control to 96% of patients after surgery and 94% after radiation therapy with long-term laryngeal preservation rate altered significantly (p = .05) in the group of patients who received radiotherapy (90.1% vs 97.4%). Conclusion The treatment of laryngeal cancer is always a compromise between oncological efficiency and preservation of function. Our data suggest that, assuming proper selection of patients, radiation therapy and surgery yield similar local control and survival rates. The functional disadvantages after surgery are moderate and clearly counterbalanced by a significant decrease in long-term laryngeal preservation rate after radiotherapeutic treatment. © 2001 John Wiley & Sons, Inc. Head Neck 23: 823,829, 2001. [source] Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C,HEPATOLOGY, Issue 4 2010Robert Roomer Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C virus (HCV) infection is a common cause of dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and can be attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to identify potential risk factors for infections during HCV treatment. In this single-center cohort study, 2,876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions, and potential risk factors for infection during HCV treatment. The baseline mean absolute neutrophil count (ANC) was 3,420 cells/,L, and 16 patients had a baseline ANC of <1,500 cells/,L. During treatment, neutropenia, which was defined as ANC <750 cells/,L, was observed in 95 patients (29.7%) and ANC <375/,L was observed in 16 patients (5%). Ninety-six infections were observed in 70 patients (21.8%). Thirteen infections (13.5%) were defined as severe. Infections were not correlated with neutropenia during treatment. Dose reductions did not lead to a decrease in infection rate. Multivariate logistic regression analysis revealed that age >55 years (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.19-3.56, P = 0.01) and baseline hyperglycemia (OR 2.17, 95% CI 1.15-4.10, P = 0.016) were associated with an increased risk of infection during HCV treatment. Cirrhosis and chronic obstructive pulmonary disease were not risk factors for infection. Conclusion: Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus have a greater risk of developing infections during HCV treatment. (HEPATOLOGY 2010) [source] Sorafenib: Where do we go from here?,HEPATOLOGY, Issue 1 2010Abby B. Siegel The approval of sorafenib as the first effective drug for the treatment of hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. A better understanding of HCC pathogenesis has led to the development of several novel targeted treatments. HCC is treated in a uniquely multidisciplinary way requiring surgeons, hepatologists, interventional radiologists, and oncologists. This review describes the molecular pathogenesis of HCC, explores current and future treatments based on these pathways, and describes how these new therapies may augment existing approaches to HCC treatment.(HHEPATOLOGY 2010;) [source] HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity In Vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus,HEPATOLOGY, Issue 3 2009Norman M. Kneteman Anti-hepatitis C virus (HCV) drug development has been challenged by a lack of experience with inhibitors inclusive of in vitro, animal model, and clinical study. This manuscript outlines activity and correlation across such a spectrum of models and into clinical trials with a novel selective nonstructural protein 5B (NS5B) polymerase inhibitor, HCV796. Enzyme assays yielded median inhibitory concentration (IC50) values of 0.01 to 0.14 ,M for genotype 1, with half maximal effective concentration (EC50s) of 5 nM and 9 nM against genotype 1a and 1b replicons. In the chimeric mouse model, a 2.02 ± 0.55 log reduction in HCV titer was seen with monotherapy, whereas a suboptimal dose of 30 mg/kg three times per day in combination with interferon demonstrated a 2.44 log reduction (P = 0.001 versus interferon alone) Clinical outcomes in combination with pegylated interferon and ribavirin have revealed additive efficacy in treatment naïve patients. Abnormal liver function test results were observed in 8% of HCV-796 patients treated for over 8 weeks, resulting in suspension of further trial activity. Conclusion: The RNA-dependent RNA polymerase inhibitor HCV796 demonstrated potent anti-HCV activity consistently through enzyme inhibition assays, subgenomic replicon, and chimeric mouse studies. Strong correlations of outcomes in the mouse model were seen with subsequent clinical trials, including a plateau in dose-related antiviral activity and additive impact from combination therapy with interferon. These outcomes demonstrate the utility of the range of in vitro and in vivo models now available for anti-HCV drug development and support the potential utility of polymerase inhibitors in future combination therapies for HCV treatment. (HEPATOLOGY 2009.) [source] Lack of response to exogenous interferon-, in the liver of chimpanzees chronically infected with hepatitis C virus,,HEPATOLOGY, Issue 4 2007Robert E. Lanford The mechanism of the interferon-alpha (IFN,),induced antiviral response is not completely understood. We recently examined the transcriptional response to IFN, in uninfected chimpanzees. The transcriptional response to IFN, in the liver and peripheral blood mononuclear cells (PBMCs) was rapidly induced but was also rapidly down-regulated, with most interferon-alpha,stimulated genes (ISGs) returning to the baseline within 24 hours. We have extended these observations to include chimpanzees chronically infected with hepatitis C virus (HCV). Remarkably, using total genome microarray analysis, we observed almost no induction of ISG transcripts in the livers of chronically infected animals following IFN, dosing, whereas the response in PBMCs was similar to that in uninfected animals. In agreement with this finding, no decrease in the viral load occurred with up to 12 weeks of pegylated IFN, therapy. The block in the response to exogenous IFN, appeared to be HCV-specific because the response in a hepatitis B virus,infected animal was similar to that of uninfected animals. The lack of a response to exogenous IFN, may be due to an already maximally induced ISG response because chronically HCV-infected chimpanzees already have a highly up-regulated hepatic ISG response. Alternatively, negative regulation may block the response to exogenous IFN,, yet it does not prevent the continued response to endogenous ISG stimuli. The IFN, response in chronically HCV-infected chimpanzees may be mechanistically similar to the null response in the human population. Conclusion: In chimpanzees infected with HCV, the highly elevated hepatic ISG expression may prevent the further induction of ISGs and antiviral efficacy following an IFN, treatment. (HEPATOLOGY 2007.) [source] Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis,,§HEPATOLOGY, Issue 6 2006Vincenzo Mazzaferro Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA,positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc],negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc,positive) groups, then randomized to IFN-, (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09,0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment. (HEPATOLOGY 2006;44:1543,1554.) [source] Quality of life in patients with primary biliary cirrhosisHEPATOLOGY, Issue 2 2004Renée Eugénie Poupon The impact of primary biliary cirrhosis (PBC) on health-related quality of life (HRQOL) is poorly documented. We assessed quality of life in a group of 276 unselected patients with PBC using the Nottingham Health Profile (NHP). This is a generic scale that assesses six major areas commonly associated with HRQOL. Data were compared with those of a sex- and age-matched control group. The associations between NHP scores and the severity of PBC were tested. Patients (86% women) had a median age of 62 years (range 33,87). Most patients were treated with UDCA. PBC patients showed a strong statistically significant difference in energy compared to controls (respectively, 40.6 vs. 22.9, P < .0001) and had worse scores for emotional reactions (22.2 vs. 16.1, P < .005). No other differences were observed. No associations of the dimension subscores were found with biochemical liver tests, histological stages, or duration of the disease. Among the signs or symptoms, fatigue was the finding most often associated with the dimension subscores. In conclusion, patients with PBC feel that their overall quality of life is worse than that of the control population. This difference is mainly due to the decrease in the subscores of energy and emotional reactions, both associated with fatigue. These effects must be taken into account by clinicians when treating these patients, as they constitute the clinical outcomes that have the most impact on patients' lifestyle and adherence to treatment. (HEPATOLOGY 2004;40:489,494.) [source] Long-term follow-up after successful interferon therapy of acute hepatitis CHEPATOLOGY, Issue 1 2004Johannes Wiegand Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-,-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. Ex vivo interferon gamma (IFN-,) ELISPOT analysis detected HCV-specific CD4+ T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8+ T-cell responses were found in 4 of 5 HLA -A2,positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. In conclusion, early treatment of symptomatic acute hepatitis C with IFN-,-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8+ (but not CD4+) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment. (HEPATOLOGY 2004;40:98,107.) [source] Hepatitis B virus variants in patients receiving lamivudine treatment with breakthrough hepatitis evaluated by serial viral loads and full-length viral sequencesHEPATOLOGY, Issue 3 2001Chun-Jen Liu Both viral loads and genome variations have been implicated in the pathogenesis of acute exacerbation of chronic hepatitis B. Hepatitis B exacerbation in patients receiving lamivudine treatment represented a unique setting to clarify their importance. Three organ recipients with posttransplantation hepatitis B exacerbation and 3 patients with chronic hepatitis B were studied. All received lamivudine treatment and their alanine aminotransferase (ALT) levels and hepatitis B virus (HBV) loads were regularly followed. Full-length genomic sequences before and during lamivudine treatment were determined in patients who had breakthrough of serum HBV DNA or elevation of serum ALT. Breakthrough of serum HBV DNA occurred after 6 to 15 months of lamivudine treatment in all. A rapid increase of viral load accompanying the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) variant was followed by hepatitis B exacerbation in each patient. The mean number of nucleotide and amino acid substitutions per genome pair was equivalent in immunosuppressed or immunocompetent patients (6.3 vs. 6.3 for nucleotide, P > .05; 6.0 vs. 6.7 for amino acid, P > .05). Changes of nucleotide and amino acid beyond the YMDD motif were distributed along the whole HBV genome but none occurred within the known B-cell epitopes and human leukocyte antigen class I, or II,restricted T-cell epitopes. Our results suggest that a resurgence of viral load rather than changes of the known immunogenic viral epitopes is more closely associated with the development of hepatitis B exacerbation after the emergence of YMDD variants in patients receiving lamivudine treatment. (HEPATOLOGY 2001;34:583-589.) [source] The clinical relevance of infancy: A progress reportINFANT MENTAL HEALTH JOURNAL, Issue 3 2008Daniel Stern In the past few decades, findings from infant observations have played a key role in the following selected areas: (a) The emphasis now is on interpersonal and intersubjective processes rather than on intrapsychic processes. This is a paradigm shift towards a two-person psychology. (b) The elaboration of the attachment domain has reoriented our views of development and treatment. (c) The success of extended home-visiting programs as a preventive measure for parents and infants at risk has brought an agonizing reappraisal of what makes prevention (and therapy) work. (d) By default, the baby's world is nonverbal. This has led to a productive reexploration of unconsciousness, especially the domain of implicit knowledge. For the future, the following are some of the areas of great promise: (a) Attachment, love and "holding" must be disentangled. (b) We must study how and when the mirror neuron system gets micro- and macroregulated. One is not always open to empathic reception. (c) The articulation between the nonverbal (implicit) with the verbal (explicit) needs far more study. (d) The nonspecific factors of psychotherapy seem to be the most important in bringing about change and prevention. We need a greater systematic study of the nonspecific. (e) The triad and quartet, and so on need further exploration. (f) There are many more, but the beauty of research is that you can't know where it will go next. [source] Kennedy's disease: pathogenesis and clinical approachesINTERNAL MEDICINE JOURNAL, Issue 5 2004K. J. Greenland Abstract Kennedy's disease, also known as spinal and bulbar muscular atrophy, is a progressive degenerative condition affecting lower motor neurons. It is one of nine neurodegenerative disorders caused by a polyglutamine repeat expansion. Affecting only men, Kennedy's disease is the only one of these conditions that follows an X-linked mode of inheritance. The causative protein in Kennedy's disease, with a polyglutamine expansion residing in the first N-terminal domain, is the androgen receptor. Research in this field has made significant advances in recent years, and with the increased understanding of pathogenic mechanisms, feasible approaches to treatments are being investigated. In Kennedy's disease research, the most significant issue to emerge recently is the role of androgens in exacerbating the disease process. On the basis of animal experiments, a viable hypothesis is that higher circulating levels of androgens in men could trigger the degeneration of motor neurons causing this disease, and that lower levels in heterozygous and homozygous women are protective. This is a major issue, as treatment of individuals affected by Kennedy's disease with testosterone has been considered a reasonable therapy by some neurologists. The rationale behind this approach relates to the fact that Kennedy's disease is accompanied by mild androgen insensitivity. It was therefore believed that treatment with high doses of testosterone might compensate for this loss of androgen action, with the added benefit of preventing muscle wasting. The current review provides an overview of recent advances in the field of Kennedy's disease research, including approaches to treatment. (Intern Med J 2004; 34: 279,286) [source] Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patientsINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Srilatha Swami Abstract Soy and its constituent isoflavone genistein inhibit the development and progression of prostate cancer (PCa). Our study in both cultured cells and PCa patients reveals a novel pathway for the actions of genistein, namely the inhibition of the synthesis and biological actions of prostaglandins (PGs), known stimulators of PCa growth. In the cell culture experiments, genistein decreased cyclooxygenase-2 (COX-2) mRNA and protein expression in both human PCa cell lines (LNCaP and PC-3) and primary prostate epithelial cells and increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA levels in primary prostate cells. As a result genistein significantly reduced the secretion of PGE2 by these cells. EP4 and FP PG receptor mRNA were also reduced by genistein, providing an additional mechanism for the suppression of PG biological effects. Further, the growth stimulatory effects of both exogenous PGs and endogenous PGs derived from precursor arachidonic acid were attenuated by genistein. We also performed a pilot randomised double blind clinical study in which placebo or soy isoflavone supplements were given to PCa patients in the neo-adjuvant setting for 2 weeks before prostatectomy. Gene expression changes were measured in the prostatectomy specimens. In PCa patients ingesting isoflavones, we observed significant decreases in prostate COX-2 mRNA and increases in p21 mRNA. There were significant correlations between COX-2 mRNA suppression, p21 mRNA stimulation and serum isoflavone levels. We propose that the inhibition of the PG pathway contributes to the beneficial effect of soy isoflavones in PCa chemoprevention and/or treatment. © 2008 Wiley-Liss, Inc. [source] The screening of the second-site suppressor mutations of the common p53 mutantsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Kazunori Otsuka Abstract Second-site suppressor (SSS) mutations in p53 found by random mutagenesis have shown to restore the inactivated function of some tumor-derived p53. To screen novel SSS mutations against common mutant p53s, intragenic second-site (SS) mutations were introduced into mutant p53 cDNA in a comprehensive manner by using a p53 missense mutation library. The resulting mutant p53s with background and SS mutations were assayed for their ability to restore the p53 transactivation function in both yeast and human cell systems. We identified 12 novel SSS mutations including H178Y against a common mutation G245S. Surprisingly, the G245S phenotype is rescued when coexpressed with p53 bearing the H178Y mutation. This result indicated that there is a possibility that intragenic suppressor mutations might restore the protein function in an intermolecular manner. The intermolecular mechanism may lead to novel strategies for restoring inactivated p53 function and tumor suppression in cancer treatment. © 2007 Wiley-Liss, Inc. [source] Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndromeINTERNATIONAL JOURNAL OF CANCER, Issue 4 2007Laura Renkonen-Sinisalo Abstract The estimated lifetime risk for endometrial carcinoma (EC) in hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is 32,60%, thus supporting surveillance. The survival rate of EC patients is, however, favourable questioning the need for surveillance. Yet, the effectiveness of gynecological surveillance remains to be shown. The 2 previously published studies were based on transvaginal ultrasound (TVUS) alone. Intrauterine biopsy has not been tested in surveillance for EC in HNPCC families. The effect of gynecological surveillance was evaluated among 175 Finnish mutation carriers. During 759 person years at risk, there were 503 surveillance visits including TVUS and intrauterine biopsy of endometrium at 94% and 74% of the visits, respectively. EC occurred in 14 cases, 11 of which were diagnosed by surveillance, 8 by intrauterine biopsies. TVUS indicated only 4 EC patients but missed 6 other cases. Intrauterine sampling detected 14 additional cases of potentially premalignant hyperplasia. The stage distribution and survival tended to be more favorable in the 14 EC cases of the surveilled group (no deaths) than in the group of 83 symptomatic mutation carriers of whom 6 died of EC, but with no statistical significance. Four cases of ovarian cancer occurred but none was detected by surveillance in TVUS examinations. In conclusion, EC surveillance in HNPCC seems more effective with endometrial biopsies than with TVUS alone. A definite improvement in survival remains to be shown. The detection of early cancer stages and premalignant lesions offers the opportunity to avoid extensive adjuvant treatment. © 2006 Wiley-Liss, Inc. [source] The involvement of hypoxia-inducible factor-1, in the susceptibility to ,-rays and chemotherapeutic drugs of oral squamous cell carcinoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Eri Sasabe Abstract The transcription factor hypoxia-inducible factor-1, (HIF-1,) is the key regulator that controls the hypoxic response of mammalian cells. The overexpression of HIF-1, has been demonstrated in many human tumors. However, the role of HIF-1, in the therapeutic efficacy of chemotherapy and radiotherapy in cancer cells is poorly understood. In this study, we investigated the influence of HIF-1, expression on the susceptibility of oral squamous cell carcinoma (OSCC) cells to chemotherapeutic drugs (cis -diamminedichloroplatinum and 5-fluorouracil) and ,-rays. Treatment with chemotherapeutic drugs and ,-rays enhanced the expression and nuclear translocation of HIF-1,, and the susceptibility of OSCC cells to the drugs and ,-rays was negatively correlated with the expression level of HIF-1, protein. The overexpression of HIF-1, induced OSCC cells to become more resistant to the anticancer agents, and down-regulation of HIF-1, expression by small interfering RNA enhanced the susceptibility of OSCC cells to them. In the HIF-1,-knockdown OSCC cells, the expression of P-glycoprotein, heme oxygenase-1, manganese-superoxide dismutase and ceruloplasmin were downregulated and the intracellular levels of chemotherapeutic drugs and reactive oxygen species were sustained at higher levels after the treatment with the anticancer agents. These results suggest that enhanced HIF-1, expression is related to the resistance of tumor cells to chemo- and radio-therapy and that HIF-1, is an effective therapeutic target for cancer treatment. © 2006 Wiley-Liss, Inc. [source] Antitumor effects of a recombinant fowlpox virus expressing Apoptin in vivo and in vitroINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Xiao Li Abstract Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. To explore the use of the Apoptin gene in cancer gene therapy, we constructed a recombinant fowlpox virus expressing the Apoptin protein (vFV- Apoptin) and compared the tumor-killing activity of the recombinant virus with that of wild-type fowlpox virus in the human hepatoma cell line HepG2. We found that although cells were somewhat resistant to the basal cytotoxic effect of wild-type fowlpox virus, infection with vFV- Apoptin caused a pronounced, additional cytotoxic effect. Furthermore, cell death and disruption of tumor integrity were apparent in the vFV- Apoptin -infected cells. We also tested whether fowlpox virus-mediated expression of Apoptin in tumor cells could stimulate an antitumor effect by injecting aggressive subcutaneous tumors derived from H22 mouse hepatoma cells in C57BL/6 mice with vFV- Apoptin. We found that fowlpox virus-mediated intratumoral expression of the Apoptin gene can induce protective and therapeutic antitumor effects and significantly increase survival. Taken together, these data indicate that infection of tumors with fowlpox virus expressing Apoptin inhibits tumor growth, induces apoptosis and may be an effective cancer treatment. © 2006 Wiley-Liss, Inc. [source] Signalling responses linked to betulinic acid-induced apoptosis are antagonized by MEK inhibitor U0126 in adherent or 3D spheroid melanoma irrespective of p53 statusINTERNATIONAL JOURNAL OF CANCER, Issue 5 2006Manuel Rieber Abstract MEK1/2 inhibitors like U0126 can potentiate or antagonize the antitumor activity of cytotoxic agents such as cisplatin, paclitaxel or vinblastine, depending on the drug or the target cells. We now investigated whether U0126, differentially regulates melanoma signaling in response to UV radiation or betulinic acid, a drug lethal against melanoma. This report shows that U0126 inhibits early response (ERK) kinase activation and cyclin A expression in wt p53 C8161 melanoma exposed to either UV radiation or betulinic acid. However, U0126 does not protect from UV damage, but counteracts betulinic acid-mediated apoptosis in the same cells. Protection from the latter drug by joint treatment with U0126 was also evident in wt p53 MelJuso melanoma and mutant p53 WM164 melanoma. The latter cells were the most responsive to betulinic acid, showing a selective decline in the cdk4 protein, without a comparable change in other key cell cycle proteins like cdc2, cdk2, cdk7 or cyclin A, prior to apoptosis-associated PARP fragmentation. Laser scanning cytometry also showed that betulinic acid induced a significant increase in chromatin condensation in WM164 melanoma irrespective of whether they were in adherent form or as multicellular spheroids. All these betulinic acid-induced changes were counteracted by U0126. Our data show for the first time that (a) cdk4 protein is an early target of betulinic acid-induced apoptosis and (b) unrestricted ERK signaling favours betulinic acid-induced apoptosis, but this is counteracted by U0126, partly through counteracting chromatin condensation and restoring Akt activation decreased by betulinic acid treatment. © 2005 Wiley-Liss, Inc. [source] B and CTL responses to the ALK protein in patients with ALK-positive ALCLINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Kamel Ait-Tahar Abstract Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) has a good prognosis compared to ALK-negative ALCL, possibly as a result of the immune recognition of the ALK proteins. The aim of our study was to investigate the presence of both a B and cytotoxic T cell (CTL) response to ALK in ALK-positive ALCL. We confirmed the presence of an antibody response to ALK in all 9 ALK-positive ALCL patients investigated. An ELISpot assay was used to detect a ,-interferon (IFN) T cell response after short term culture of mononuclear blood cells with 2 ALK-derived HLA-A*0201 restricted peptides: ALKa and ALKb. A significant ,-IFN response was identified in all 7 HLA-A*0201-positive ALK-positive ALCL patients but not in ALK-negative ALCL patients (n = 2) or normal subjects (n = 6). CTL lines (>95% CD8-positive) raised from 2 ALK-positive ALCL patients lysed ALK-positive ALCL derived cell lines in a MHC-Class I restricted manner. This is the first report of both a B cell and CTL response to ALK in patients with ALK-positive ALCL. This response persisted during long-term remission. The use of modified vaccinia virus Ankara (MVA) to express ALK is also described. Our findings are of potential prognostic value and open up therapeutic options for those ALK-positive patients who do not respond to conventional treatment. © 2005 Wiley-Liss, Inc. [source] Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancerINTERNATIONAL JOURNAL OF CANCER, Issue 3 2002Barbara Bachtiary Abstract To obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin-fixed, paraffin-embedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal-amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression-free survival (PFS) and cervical cancer-specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety-six patients (90.6%) were HPV-positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment. © 2002 Wiley-Liss, Inc. [source] Parental medical neglect in the treatment of adolescents with anorexia nervosaINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2001Victor Fornari Abstract Objective Although childhood sexual abuse has been a frequent focus of research on eating disorders, other forms of maltreatment have been less commonly reported. Parental medical neglect is examined in this study as having serious consequences for the treatment and prognosis of patients with anorexia nervosa. Method Two case studies illustrate parental interference with treatment in which Child Protective Services (CPS) had to be involved in compliance with state law. Two adolescent females who were admitted for treatment for anorexia nervosa are presented. Results In both cases, the parents refused to comply with the recommendations of the treatment team, placing their children's health in jeopardy. In compliance with reporting guidelines, CPS was notified in both cases. Conclusions Clinicians who treat minors with anorexia nervosa must consider parental compliance with treatment. Indications for the involvement of CPS are outlined. Optimally, this notification can ensure that the patient and family receive the requisite treatment. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 29: 358,362, 2001. [source] Reinforcement and antioxidation effects of fullerenol-containing natural rubberJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2010Hiroaki Kondo Abstract Natural rubber (NR) containing fullerenol, C60-OH, was prepared by two methods; one by mixing C60-OH aqueous solution to NR latex followed by coagulation (wet method) and the other by mixing C60-OH powder with solid rubber by an open roll mixer (dry method). C60-OH mixed by wet method was homogeneously dispersed in the rubber, while one mixed by dry method was particles in the size up to 70 ,m. The former exhibited large reinforcing and antiaging effect than the latter. The large antiaging effect was explained by the finding that C60-OH had large radical scavenging ability and gel forming ability during heat treatment. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] Influence of high temperature and pressure ammonia solution treatment on interfacial behavior of carbon fiber/epoxy resin compositesJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2009L. H. Meng Abstract The method of high temperature and pressure ammonia solution treatment to improve the interfacial performances of carbon fiber/epoxy composites is discussed in this study. Besides, the influence of high temperature and pressure ammonia solution treatment on carbon fiber and its reinforced epoxy composite interface performance were studied. The untreated and treated carbon fibers were characterized by monofilament tensile test, X-ray photoelectron spectroscopy (XPS), and atomic force microscope (AFM). The interfacial adhesion of the untreated and treated carbon fibers reinforced epoxy resin composites were also evaluated by interface shear strength (IFSS) test, interlaminar shear strength (ILSS) test, and fracture morphology analysis. It was found that the interfacial adhesion of composites increased greatly after high temperature and pressure ammonia solution treatment. The improvement of interfacial adhesion was attributed to the increase of polar functional groups and surface roughness of carbon fibers surface after treatment. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009 [source] | ||||||||||||||||||||||||||||||||||||||||||||||