bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice
Authors: Lui S L , Tsang R , Wong D , Chan K W , Chan T M , Fung P C W , Lai K N 
Published: October 2002

Mycophenolate mofetil (MMF), an immunosuppressive drug commonly used in organ transplantation, is increasingly being used to treat autoimmune diseases including systemic lupus erythematosus (SLE). Excessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesisof lupus nephritis. We evaluated the effect of MMF on the severity of nephritis and the production of NO in lupus-prone MRL/lpr mice. Eight-week-old female MRL/lpr mice (n = 20) were treated with MMF (100 mg/kg/day) by oral gavage for 12 weeks. Control mice (n = 20) received vehicle on the same schedule. The mice were killed after 12 weeks of treatment. Treatment with MMF significantly decreased the amount of proteinuria, prolonged survival and reduced the histological severity of glomerulonephritis.Urinary nitrite/nitrate excretion in the MMF-treated mice was significantly reduced during the first 8 weeks of treatment. However, by the end of the 12 weeks' treatment period, there was no significant difference between vehicle and MMF-treated mice in terms of urinary nitrite/nitrate excretion, intra-renal production of NO, expression of iNOS protein and induction of iNOS mRNA. We conclude that MMF is effective in attenuatingthe severity of nephritis in MRL/lpr mice. The beneficial effects of MMF on lupus nephritis during the early phase of the disease might be partly attributed to the inhibition of NO production. The inhibitory effect of MMF on NO production diminishes as the disease progresses. MMF probably has additional, as yet undefined mode of actions to fully account for its beneficial effects on lupus nephritis.
Development and assessment of a World Wide Web site for systemic lupus erythematosus patient information
Authors: Young S P , Henderson E , Cheseldine D L , Wilson A S , Skan J , Heaton S , Bowman S J , Situnayake D , Bacon P A , Southwood T R , Gordon C 
Published: October 2002

Patient education is an important component of the management of chronic diseases such as SLE. We have investigated the value of the World Wide Web as a medium for delivery of SLE patient information. Volunteers recruited from the clinic and from the website completed interviews and questionnaires aimed at defining their information needs. A new website was then established and its impact on users tested using knowledge questionnaires. The new website was used extensively (20–30 users each day) over the 24 month period of study until April 2001. A total of 510 participants completed an online questionnaire that showed that for some users it was their first use of the internet to gather lupus information, but the majority (58.9%) accessed it at least monthly for this purpose. We also found that, while most users (56.9%) found current disease information was at an appropriate level, 37.5% thought it was too basic. Knowledge questionnaires from 42 participants before and after using the site showed a significant rise in users’ knowledge of the areas covered by the site. As far as we are aware this study is the first to show that a patient-oriented website can have a positive effect on disease knowledge. The relative ease with which good quality information can be disseminated via the web suggests that this medium is likely to be less costly and perhaps more educationally effective than printed information, and so is likely to become a primary vehicle for patient education. The website tested can be found at: www.rheumatology.bham.ac.uk/lupus/intro.html
Systemic lupus erythematosus presented as non-inflammatory necrotizing vasculopathy-induced ischemic glomerulopathy and small vessels-related ischemic cardiomyopathy
Authors: Sung J M , Hsu S C , Chen F F , Huang J J 
Published: October 2002

The clinical significance of lupus non-inflammatory necrotizing vasculopathy (NINV) is not well established. For example, since lupus renal NINV is usually reported to coexist with proliferative and active glomerulonephritis, it is difficult to demonstrate the role of NINV on renal pathophysiology. Here we report a 16-year-old SLE boy with renal NINV presenting as ischemic glomerulopathy and small vessels-related ischemic heart failure. The renal biopsy demonstrated mild proliferative glomerulonephritis and NINV initially, and one month later repeated renal biopsy showed NINV with ischemic glomerulopathy. These findings established that NINV, but not proliferative glomerulonephritis, was responsive for his acute renal failure (ARF). Another interesting question is about the pathophysiology of his myocardial dysfunction. This patient presented typical angina and congestive heart failure (CHF). Echocardiograms and ventriculography revealed dilatation of four chambers and low ejection fraction. Serial electrocardiograms demonstrated evolutionary ischemic changes. Coronary angiography revealed no abnormality of large vessels. These findings suggested small vascular lesions-induced myocardial ischemia was the underlying mechanism of dilated cardiomyopathy. As myocardial biopsy was not done in our case, we could only speculate, but not prove, that the NINV observed in renal biopsy may also involve in cardiac microvascular beds. Nevertheless, this interesting case emphasized the role of obliterative small vascular lesions in the pathophysiologyof ARF and myocardial dysfunction. The patient was treated with high-dose corticosteroid, plasma infusion and hemodialysis. His cardiac function improved gradually, however the renal function did not recover.
Psychiatric effects of traumatic brain injury events in Cambodian survivors of mass violence
Authors: Mollica Richard F. , Henderson David C. , Tor Svang 
Published: October 2002

BackgroundThe prevalence of brain injury and its effects in populations exposed to war violence has not been studied in recent years.AimsTo examine the association between traumatic brain injury events and psychiatric symptoms of major depression and post-traumatic stress disorder (PTSD) in Cambodian survivors of mass violence.MethodThe population comprised a multi-stage random sample of Cambodian refugees livingin a Thai refugee camp. The main results analysed the relationship between six categories of trauma events and psychiatric symptoms of depression and PTSD during two time periods.ResultsAlmost 15 000 trauma events were reported (n=13481, Pol Pot period;n=1249, past year). Traumatic brain injury was most common in the highly educated and in individuals with the highest levels of cumulative trauma. Of all trauma categories, traumatic brain injury revealed the strongest association with symptoms of depression, and a weaker association with PTSD. Brain injury represented 4% of the total number of traumatic events for both time periods, contributing 20% of the total symptom score for depression and 8% of that for PTSD.ConclusionsClinical identification and treatment of traumatic brain injuries in highly traumatised populations must be maintained in order to develop a new public health model for their treatment.
Utility of Troponin I in Patients with Cocaine‐associated Chest Pain
Authors: Kontos Michael C. , Anderson F. Philip , Ornato Joseph P. , Tatum James L. , Jesse Robert L. 
Published: October 2002

AbstractBaseline electrocardiogram abnormalities and market elevations not associated with myocardial necrosis make accurate diagnosis of myocardial infarction (MI) difficult in patients with cocaine‐associated chest pain. Troponin sampling may offer greater diagnostic utility in these patients. Objective: To assess outcomes based on troponin positivity in patients with cocaine chest pain admitted for exclusion of MI. Methods: Outcomes were examined in patients admitted for possible MI after cocaine use. All patients underwent a rapid rule‐in protocol that included serial sampling of creatine kinase (CK), CK‐MB, and cardiac troponin I (cTnI) over eight hours. Outcomes included CK‐MB MI (CK‐MB ≥ 8 ng/mL with a relative index [(CK‐MB × 100)/total CK] ≥ 4, cardiac death, and significant coronary disease (≥50%). Results: Of the 246 admitted patients, 34 (14%) met CK‐MB criteria for MI and 38 (16%) had cTnI elevations. Angiography was performed in 29 of 38 patients who were cTnI‐positive, with significant disease present in 25 (86%). Three of the four patients without significant disease who had cTnI elevations met CK‐MB criteria for MI, and the other had a peak CK‐MB level of 13 ng/mL. Sensitivities, specificities, and positive and negative likelihood ratios for predicting cardiac death or significant disease were high for both CK‐MB MI and cTnI and were not significantly different. Conclusions: Most patients with cTnI elevations meet CK‐MB criteria for MI, as well as have a high incidence of underlying significant disease. Troponin appears to have an equivalent diagnostic accuracy compared with CK‐MB for diagnosing necrosis in patients with cocaine‐associated chest pain and suspected MI.
Expression of Multidrug Resistance GenesMVP,MDR1, andMRP1Determined Sequentially Before, During, and After Hyperthermic Isolated Limb Perfusion of Soft Tissue Sarcoma and Melanoma Patients
Authors: Stein Ulrike , Jürchott Karsten , Schläfke Matthias , Hohenberger Peter 
Published: October 2002

PURPOSE: Isolated, hyperthermic limb perfusion (ILP) with recombinant human tumor necrosis factor alpha and melphalan is a highly effective treatment for advanced soft tissue sarcoma (STS) and locoregional metastatic malignant melanoma. Multidrug resistance (MDR)-associated genes are known to be inducible by heat and drugs; expression levels of the major vault protein (MVP), MDR1, and MDR-associated protein 1 (MRP1) were determined sequentially before, during, and after ILP of patients.PATIENTS AND METHODS: Twenty-one STS or malignant melanoma patients were treated by ILP. Tumor tissue temperatures were recorded continuously and ranged from 33.4°C initially to peak values of 40.4°C during ILP. Serial true-cut biopsy specimens from tumor tissues were routinely microdissected. Expression analyses for MDR genes were performed by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry.RESULTS: In 83% of the patients, MVP expression was induced during hyperthermic ILP. MVP-mRNA inductions often paralleled the increase in temperature during ILP. Increased MVP protein expressions either were observed simultaneously with the MVP-mRNA induction or were delayed until after the induction at the transcriptional level. Inductions of MDR1 and MRP1 were observed in only 13% and 27% of the specimens analyzed. Temperatures and drugs applied preferentially led to an induction of MVP and were not sufficient to induce MDR1 and MRP1 in the majority of tumors.CONCLUSION: This study is the first to analyze the expression of MDR-associated genes sequentially during ILP of patients and demonstrates that treatment might lead to increased levels of MVP, whereas enhanced levels of MDR1 and MRP1 remain rare events.
Symptom Experiences: Perceptual Accuracy Between Advanced-Stage Cancer Patients and Family Caregivers in the Home Care Setting
Authors: Lobchuk Michelle M. , Degner Lesley F. 
Published: October 2002

PURPOSE: This study used a comparative descriptive design to compare family caregivers’ and advanced-stage cancer patients’ perceptions of patients’ multidimensional symptom experiences on presence, frequency, severity, and distress. PATIENTS AND METHODS: A convenience sample of 98 dyads, composed of advanced-stage heterogeneous cancer patients and their caregivers, completed the Memorial Symptom Assessment Scale in the home care setting on a one-time basis. This scale is a 32-item Likert-type scale for assessing the presence, frequency, severity, and distress arising from symptoms in cancer patients. RESULTS: There was confirmation of trends previously described in related studies where, for example, caregivers tend to overreport on symptom experiences. However, the degree of absolute difference between patient and caregiver responses was normally around 1 unit (on a theoretical range of 0 to 4 units). Levels of patient-caregiver agreement were better on more concrete questions related to symptom frequency, severity, and distress than on broad questions related to the presence of a symptom. Patients and caregivers achieved better levels of agreement on physical versus psychological symptoms. CONCLUSION: The findings indicated that family caregivers can provide reasonable proxy or complementary reports on patient symptom experiences of frequency, severity, and distress. However, family caregivers have greater difficulty in achieving high levels of accuracy on psychological versus physical symptoms.
Phase I Trial of Intravesical Gemcitabine in Bacillus Calmette-Guérin–Refractory Transitional-Cell Carcinoma of the Bladder
Authors: Dalbagni Guido , Russo Paul , Sheinfeld Joel , Mazumdar Madhu , Tong William , Rabbani Farhang , Donat Machelle S. , Herr Harry W. , Sogani Pramod , dePalma Dominique , Bajorin Dean 
Published: October 2002

PURPOSE: The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg. RESULTS: Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology). CONCLUSION: Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.
Factorial Design Considerations
Authors: Green Stephanie , Liu Ping-Yu , O’Sullivan Janet 
Published: October 2002

PURPOSE: Factorial designs may be proposed to test extra questions within a clinical trial. A common approach to sample size and analysis for factorial trials assumes no statistical interactions and does not adjust for multiple testing. This investigation considered the trade-off between potential gains from testing more questions with fewer patients versus how often a factorial trial might arrive at an incorrect conclusion. METHODS: A simulation study of a 2 × 2 design (observation v chemotherapy v radiation therapy v the combination) was performed under various conditions, including effect of one, both, or neither treatment and absence or presence of statistical interaction (effect of one treatment differed according to the presence of the other). Three analysis approaches were investigated, one assuming no interaction, a second testing first for interaction, and the third testing for interaction as well as adjusting for multiple testing. The approaches were compared with respect to the probability of selecting the correct treatment arm. RESULTS: No one approach was superior. Testing for interaction was beneficial in some settings but detrimental in others. Under some scenarios, the factorial design improved efficiency, but under others, all three approaches resulted in poor probability of selecting the correct treatment arm at the end of the trial. CONCLUSION: Extra efficiency is possible, but it is difficult to predict when favorable conditions exist. If a factorial design is used, potential efficiency gains should be weighed against potential loss of power to arrive at the correct conclusion under possible scenarios of interest.
Treatment of Unresectable and Metastatic Hepatoblastoma: A Pediatric Oncology Group Phase II Study
Authors: Katzenstein Howard M. , London Wendy B. , Douglass Edwin C. , Reynolds Marleta , Plaschkes Jack , Finegold Milton J. , Bowman Laura C. 
Published: October 2002

PURPOSE: To estimate the disease-response rate, proportion of patients whose tumors can be made resectable, event-free survival (EFS), and toxicity in children with unresectable or metastatic hepatoblastoma (HB) after sequential treatment with the following: (1) carboplatin (CARBO); (2) CARBO, vincristine, and fluorouracil (CARBO-VCR-5-FU); and (3) high-dose cisplatin and etoposide (HDDP-ETOP). PATIENTS AND METHODS: Thirty-three assessable patients with stage III (n = 22) and stage IV (n = 11) HB were treated sequentially with one course of CARBO (700 mg/m2), followed by three courses of CARBO (700 mg/m2), day 0; 5-FU (1,000 mg/m2/d), by continuous infusion days 0 to 2; and VCR (1.5 mg/m2), days 0, 7, and 14. After that therapy, patients whose tumors were resectable underwent surgery and then received two additional courses of CARBO-VCR-5-FU. Children whose tumors remained unresectable after CARBO-VCR-5-FU or who demonstrated no response or progressive disease during this therapy received two courses of HDDP (40 mg/m2/d), days 1 to 5; and ETOP (100 mg/m2/d), days 2 to 4. RESULTS: Five-year EFS estimates were 59% ± 11% for stage III disease (n = 22) and 27% ± 16% for stage IV disease (n = 11), respectively (P = .037). Twenty-seven (82%) of 33 patients had at least a partial response to chemotherapy; 18 (55%) of 33 responded to CARBO; 24 (80%) of 30 responded to CARBO and CARBO-VCR-5-FU; and nine (75%) of 12 responded to HDDP-ETOP. Surgical resection was achieved in 19 (58%) of 33 patients, including 15 (68%) of 22 stage III patients and four (36%) of 11 stage IV patients. Five-year EFS for patients whose tumors were completely resected was 79% ± 10%. CONCLUSION: Patients treated sequentially with CARBO, CARBO-VCR-5-FU, and HDDP-ETOP had response rates and EFS comparable to other therapeutic regimens. This regimen is effective in treating localized, unresectable HB and potentially has less toxicity than other regimens. Novel approaches are needed for patients with metastatic disease.
Phase II Evaluation of Low-Dose Oral Etoposide for the Treatment of Relapsed or Progressive AIDS-Related Kaposi’s Sarcoma: An AIDS Clinical Trials Group Clinical Study
Authors: Evans Scott R. , Krown Susan E. , Testa Marcia A. , Cooley Timothy P. , Von Roenn Jamie H. 
Published: October 2002

PURPOSE: Liposomal anthracyclines and paclitaxel are considered the best available cytotoxic therapies for Kaposi’s sarcoma (KS), but relapse is common. To identify new interventions for relapsed or progressive KS, a phase II study of low-dose etoposide to assess its toxicity and efficacy was conducted. PATIENTS AND METHODS: Thirty-six patients with high-risk KS were treated with oral etoposide 50 mg/d for 7 consecutive days of every 2-week cycle. All patients’ disease had relapsed or progressed after prior combination chemotherapy or anthracycline therapy. For patients without a complete or partial response after two cycles of therapy and no toxicity greater than grade 2, the dose of etoposide was escalated to 100 mg/d orally on days 1 to 7 of each 14-day cycle. Treatment-related and disease-specific quality of life was evaluated using patient reports on the General Health Self-Assessment Form and a KS-specific measure. RESULTS: One patient achieved a complete response, 12 patients had a partial response (overall response rate, 36.1%), and stable disease was observed in 12 patients (33.3%). Tumor responses were seen in all disease sites. Fourteen patients had their dose escalated, of whom five responded. The median time to response was 17.7 weeks; the median duration of response was 25 weeks. The most frequent hematologic abnormality was neutropenia, which was grade 4 in seven patients and grade 3 in six. Opportunistic infections occurred in eight patients during the treatment period. Both response to treatment and toxicity influenced patient-reported quality of life. CONCLUSION: We conclude that low-dose oral etoposide at a dose of 50 mg/d is safe and effective for the treatment of refractory or progressed AIDS-related KS and has an overall positive effect on the quality of life of responding patients.
Retinoid X Receptor Dominates the Nuclear Import and Export of the Unliganded Vitamin D Receptor
Authors: Prüfer Kirsten , Barsony Julia 
Published: October 2002

AbstractLiganded and unliganded vitamin D receptors (VDRs) carry out distinct functions; both types of functions require heterodimerization with retinoid X receptors (RXRs). Our recent studies with fluorescent protein chimeras of VDR and RXR, termed GFP-VDR, YFP-RXR, and RXR-BFP, indicated that RXR regulates VDR functions in part by regulating subcellular localization. Here we explored the mechanisms of this regulation. Photobleaching experiments demonstrated that YFP-RXR and both unliganded and liganded GFP-VDR shuttle constantly between nucleus and cytoplasm. To characterize RXR import, we identified a nuclear localization sequence (NLS) in the DNA-binding domain. Mutations in this NLS caused predominant cytoplasmic localization of nlsYFP-RXR and prevented transcriptional activity. The nlsRXR-BFP retained unliganded GFP-VDR in the cytoplasm and reduced baseline transcriptional activity. After calcitriol exposure, however, both GFP-VDR and nlsRXR-BFP entered the nucleus. We characterized receptor export rates and mechanisms using permeabilization experiments. Mutations in the calreticulin binding region slowed both GFP-VDR and YFP-RXR export. Coexpression of RXR-BFP slowed the export of unliganded GFP-VDR, whereas calcitriol treatment tripled the rate of GFP-VDR export. Treatment with leptomycin B, an inhibitor of CRM-1 receptor-mediated export, inhibited export of unliganded GFP-VDR but did not influence export of liganded GFP-VDR or YFP-RXR. Leptomycin B added before calcitriol similarly decreased hormone-induced luciferase activity but was ineffective when added subsequent to calcitriol. These results indicate that the unliganded and liganded VDR interact differently with the import and export receptors and with RXR. Most likely, the regulation of VDR nuclear import by RXR is essential for ligand-independent functions.