bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colonization of HIV-infected outpatients in Taiwan with methicillin-resistant and methicillin-susceptible Staphylococcus aureus
Authors: McDonald L Clifford , Lauderdale Tsai-Ling , Lo Hsiu-Jung , Tsai Jih-Jin , Hung Chien-Ching 
Published: June 2003

To better understand the epidemiology of bacterial pathogens with particular public health importance in Taiwan, we determined the prevalence of nasal colonization with methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a cohort of HIV-infected patients attending two hospital outpatient departments. All HIV-infected patients followed regularly between May and September 1999 were enrolled and cultures of the anterior nares were performed using a dry sponge swab. All confirmed S. aureus isolates underwent antimicrobial susceptibility testing using disk diffusion according to recommendations of the National Committee for Clinical Laboratory Standards. Of a total of 162 outpatients studied, 48 (30%) were found colonized with S. aureus including 39 (24%) colonized with MSSA and 9 (6%) colonized with MRSA. The only factor associated with MSSA colonization was receipt of trimethoprim-sulphamethoxazole which appeared protective (relative risk 0.4, 95% confidence interval [CI95] 0.2-0.78, P = 0.006). In contrast, ciprofloxacin use was an independent risk factor for MRSA colonization (conditional odds ratio [OR] 11.9, CI95 1.8-77.8, P = 0.010) along with a one-quartile reduction in CD4 count (OR 3.9, CI95 1.1-14.3, P = 0.04). Although MRSA colonization was not associated with hospitalization within the previous three months, the multi-drug resistance pattern of MRSA isolates suggests strains were at some point acquired in the healthcare setting. Our study shows that the rate of S. aureus colonization in Taiwanese HIV-infected outpatients is 30%. Low CD4+ counts are most likely associated with other unmeasured risk factors for MRSA. Antimicrobial use may function alternatively as a protective or risk factor for colonization with S. aureus, depending upon the drugs involved and resistance encountered. Fluoroquinolone use may have an important role in the spread of MRSA from inpatient to outpatient settings.
Atovaquone–Proguanil for Prophylaxis and Treatment of Malaria
Authors: Marra Fawziah , Salzman James R , Ensom Mary HH 
Published: June 2003

OBJECTIVE: To review the currently available information on atovaquone–proguanil for treatment and prophylaxis of malaria. DATA SOURCES: A MEDLINE search was conducted from 1966 to February 2003 using key phrases Malarone, atovaquone, proguanil, and malaria. Further articles were identified from a manual search of the references of identified articles. STUDY SELECTION AND DATA EXTRACTION: English-language studies with animal and human data evaluating preclinical pharmacology, human studies on pharmacokinetics, and clinical trials were evaluated. Relevant data were extracted from identified articles. DATA SYNTHESIS: Atovaquone–proguanil has been evaluated for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum in 8 clinical trials. In these studies, treatment with atovaquone–proguanil led to a higher (87–100% vs. 72–88%) or equally effective (94–100% vs. 90–100%) cure rate than the comparator antimalarial agents. Atovaquone–proguanil has been evaluated for prophylaxis of malaria in 6 clinical trials. In the 4 placebo-controlled trials for semi-immune residents or nonimmune migrants, the prophylaxis success rates in the atovaquone–proguanil and placebo arms ranged from 98% to 100% and 48% to 82%, respectively. The prophylaxis with success rates were similar among the 2 arms when atovaquone–proguanil was compared with other antimalarial regimens in nonimmune travelers. Atovaquone–proguanil was well tolerated in these clinical trials. CONCLUSIONS: Atovaquone–proguanil is a safe and effective alternative to current recommended regimens for prophylaxis and treatment of malaria.
Olanzapine for Psychotic and Behavioral Disturbances in Alzheimer Disease
Authors: Schatz Robin A 
Published: June 2003

OBJECTIVE: To evaluate the efficacy and safety of olanzapine for the treatment of psychotic and behavioral disturbances in Alzheimer disease. DATA SOURCES: MEDLINE (1966–January 2003) and Science Citation Index searches were performed. Key search terms included olanzapine, Alzheimer(s), and dementia. DATA SYNTHESIS: Four trials of olanzapine and subsequent post hoc analyses were reviewed. Three trials found a benefit associated with olanzapine use, but a fourth trial did not. CONCLUSIONS: Olanzapine appears to be effective in treating psychotic and behavioral disturbances associated with Alzheimer disease. However, the most appropriate dose remains to be determined. The benefit of olanzapine therapy must be weighed against the adverse effect profiles of olanzapine and alternative treatment options.
Severe Hypersensitivity Pneumonitis Associated with Anagrelide
Authors: Raghavan Murugan , Mazer Mark A , Brink David J 
Published: June 2003

OBJECTIVE: To report a case of severe life-threatening hypersensitivity pneumonitis temporally associated with the use of anagrelide in a patient with myeloproliferative disorder. CASE SUMMARY: A 60-year-old white woman with chronic myeloid leukemia who had been treated with hydroxyurea for 7 years was offered anagrelide to control thrombocytosis. She developed severe hypersensitivity pneumonitis soon after the drug was initiated and required intubation and mechanical ventilation. A high-resolution computed tomography scan of the chest demonstrated extensive multifocal ground glass attenuation and patchy alveolar consolidation involving both lungs. Bronchoalveolar lavage revealed a preponderance of lymphocytes, suggesting hypersensitivity phenomenon, but was otherwise negative for malignancy and other causes of interstitial pneumonitis. An objective causality assessment revealed that an adverse drug event was probable. Discontinuation of anagrelide and hydroxyurea, and institution of corticosteroid therapy resulted in dramatic improvement. DISCUSSION: To our knowledge, this is the first case report of severe hypersensitivity pneumonitis closely related to anagrelide therapy. Pulmonary infiltrates have rarely been noted in patients treated with anagrelide. Anagrelide does not depress white blood cell production, causes mild anemia, and is devoid of the leukemogenic potential characteristic of radioactive phosphorus and other alkylating agents. Common adverse effects to anagrelide include headache, nausea, diarrhea, peripheral edema, and palpitations. Frank congestive heart failure and cardiomyopathy have occurred in a small number of patients, but severe pulmonary adverse effects have not emerged as a frequent problem. CONCLUSIONS: Vigilance is advised in patients who develop dyspnea while taking anagrelide and hydroxyurea. Healthcare providers need to be aware of the possibility of the development of serious life-threatening hypersensitivity pneumonitis. These patients may benefit from serial chest X-rays, pulmonary function testing, and echocardiography.
Effect of co‐administration of retinoids on rat embryo development in vitro
Authors: Ritchie Helen E. , Brown‐Woodman Patricia D. , Korabelnikoff Ann 
Published: June 2003

AbstractBACKGROUNDExcess retinyl palmitate (vitamin A) induces a variety of malformations in many mammalian species, yet retinyl palmitate is not thought to be the proximate teratogen. Many metabolites are generated after oral dosing several of which are, individually teratogenic. It is not known whether these metabolites when present simultaneously interact in an additive or synergistic manner.METHODSWhole rat embryos were cultured with retinol, all‐trans retinoic acid (tRA), 4‐oxo all‐trans retinoic acid (4otRA) or 9‐cis retinoic acid (9cRA). Retinoids were added singly or in paired combinations at the start of culture and embryos were examined for evidence of dysmorphogenesis at the end of culture. Retinoids were added at both subthreshold and supra‐threshold concentrations.RESULTSCo‐administration of subthreshold concentrations of tRA and 4otRA, retinol and tRA or 4otRA and 4otRA and 9cRA resulted in a greater frequency of abnormal embryos compared to single administration of each retinoid.CONCLUSIONSKnowledge of the way in which retinyl palmitate metabolites interact should refine our ability to predict risk from a potentially teratogenic event e.g., accidental overdose with RP during human pregnancy. Birth Defects Research (Part A) 67444–451, 2003. © 2003 Wiley‐Liss, Inc.
Papillary microcarcinoma of the thyroid—Prognostic significance of lymph node metastasis and multifocality
Authors: Chow Sin‐Ming , Law Stephen C. K. , Chan John K. C. , Au Siu‐Kie , Yau Stephen , Lau Wai‐Hon 
Published: June 2003

AbstractBACKGROUNDIt is known that patients with papillary microcarcinoma (PMC) of the thyroid gland have a very favorable prognosis. The rising incidence of PMC among papillary thyroid carcinoma (PTC) necessitates the identification of prognostic factors and the formulation of treatment protocols.METHODSThe authors conducted a retrospective analysis of 203 patients with PMC who were diagnosed on or before 1999 and were treated at the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong.RESULTSThe cause specific survival, locoregional (LR) failure free survival, and distant metastases failure free survival rates at 10 years were 100%, 92.1%, and 97.1%, respectively. Five patients had lung metastases; 2 patients died of their metastases 12.9 years and 14.8 years after diagnosis, and 3 patients achieved clinical remission after radioiodine (RAI) treatment. Twelve patients had LR recurrences. Patients with LR recurrence were highly salvageable with a combination of surgery, RAI treatment, and external radiotherapy; all but one (who refused treatment) were alive without disease at last follow‐up. Multivariate analyses did not reveal any independent prognostic factor for survival. The risk of cervical lymph node (LN) recurrence increased 6.2‐fold (P= 0.01) and 5.6‐fold (P= 0.02) when LN metastases and multifocal disease were present at diagnosis. RAI ablation reduced the LN recurrence rate to 0.27 (P= 0.04). The presence of LN metastasis increased the rate of distant metastasis 11.2‐fold (P= 0.03). Age was not a significant factor in predicting disease recurrence or survival. Subdivision by tumor sizes ≤ 5 mm and > 5 mm did not affect the outcome, but no patient with tumors ≤ 5 mm had mortality related to PMC.CONCLUSIONSDespite the overall excellent prognosis for patients with PMC, PMC was associated with a 1.0% disease‐related mortality rate, a 5.0% LN recurrence rate, and a 2.5% distant metastasis rate. Therefore, the treatment of patients with PMC should be no different from the treatment of patients with conventional PTC: i.e., complete surgery with consideration for RAI and/or external radiation therapy if poor prognostic factors are present. Cancer 2003;98:31–40. © 2003 American Cancer Society.DOI 10.1002/cncr.11442
Evidence of a preferred molecular pathway in patients with synchronous colorectal cancer
Authors: Dykes Sharon L. , Qui Hongming , Rothenberger David A. , García‐Aguilar Julio 
Published: June 2003

AbstractBACKGROUNDA small proportion of patients with colorectal carcinoma (CRC) have synchronous tumors at the time of diagnosis. A subset of sporadic CRCs display microsatellite instability (MSI) that is associated with MLH1 silencing due to promoter methylation. In the current study, the authors investigated the proportion of tumors with MSI in patients with synchronous colorectal carcinoma (SCRC) and the concordance in MSI status among tumors in a given individual. In addition, the authors examined MLH1 and MSH2 expression and MLH1 promoter methylation in SCRCs.METHODSThe current study included 77 patients, with a combined total of 170 invasive SCRCs, who were identified from a database of 2884 patients with CRC. Instability was determined by polymerase chain reaction (PCR) amplification using a set of five markers. Tumors that were unstable at two or more markers were considered unstable (MSI); otherwise, they were considered microsatellite stable (MSS). Expression of MLH1 and MSH2 was determined by immunohistochemistry. Methylation of the MLH1 gene promoter was determined by a methylation‐specific PCR assay. Statistical comparisons were made using the chi‐square test or the Student t test.RESULTSOf the 77 patients in the study, 21 (27%) had a family history of hereditary nonpolyposis colon carcinoma–related malignancy, but none fulfilled the Amsterdam II criteria. Fifty‐four of 170 tumors (32%) were found to be MSI. Patients with MSI tumors were older and more frequently female. All but 1 MSI tumor lacked expression of MLH1 (n = 44) or MSH2 (n = 8), or both (n = 1). All MLH1‐negative tumors, compared with only 3 MLH1‐positive tumors, were methylated at the MLH1 promoter. Most patients (n = 67; 87%) had either all MSS tumors (n = 48; 62%) or all MSI tumors (n = 19; 25%); 10 patients (13%) had both MSS and MSI tumors. The observed MSI/MSS distribution was significantly different from the distribution expected based on an assumption of independence (P < 0.0001).CONCLUSIONSThere is a strong concordance in MSI/MSS status among tumors in the same individual. This finding suggests that the tumors in patients with SCRC develop along a preferred molecular pathway. Cancer 2003;98:48–54. © 2003 American Cancer Society.DOI 10.1002/cncr.11445
Distribution of HER‐2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma
Authors: Høgdall Estrid V. S. , Christensen Lise , Kjaer Susanne K. , Blaakaer Jan , Bock Johannes E. , Glud Eva , Nørgaard‐Pedersen Bent , Høgdall Claus K. 
Published: June 2003

AbstractBACKGROUNDThe HER‐2 (Human Epidermal Growth factor receptor‐2, also known as c‐erb‐2/neu) protooncogene encodes a transmembrane receptor protein,Mr185,000. Studies have shown that the HER‐2 oncogene is overexpressed in approximately 25–30% of ovarian carcinoma (OC) cases, but to the authors' knowledge, to date no consensus regarding overexpression and prognosis has been possible. The objective of the current study was first to analyze the presence of HER‐2 overexpression in tissue from Danish OC patients and correlate the distribution of HER‐2 overexpression with clinical and biochemical data and second to investigate the value of HER‐2 overexpression as a prognostic marker in OC and to compare this value with the prognostic value of other biochemical markers.METHODSThe study population was comprised of the first 181 patients diagnosed with epithelial OC who were included in the MALOVA study. The staining procedure for HER‐2 overexpression was performed using the p185 antibody.RESULTSHER‐2 overexpression was found in 95 of the 181 investigated cases (52.5%), in which 71 carcinomas (39.2%) were weakly positive (1+) and 24 carcinomas (13.3%) were moderately (2+) to intensely positive (3+). Increased HER‐2 expression was found to be correlated with reduced survival. Significant differences in survival between patients with (1+, 2+, and 3+) and those without HER‐2 overexpression were found for patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I, Stage III, and Stage III/IV OC (Stage I:P= 0.021; Stage III:P= 0.0078; and Stage III/IV:P= 0.0054). Multivariate survival analyses including all 181 OC patients demonstrated that HER‐2 overexpression is a prognostic marker (P= 0.003) together with disease stage, serum tetranectin level, and patient age. For patients with Stage III OC, the only independent prognostic factors detected were HER‐2 overexpression (P= 0.009) and serum tetranectin level (P≤ 0.0001).CONCLUSIONSThe results of the current study show that HER‐2 overexpression has prognostic value both in univariate and multivariate survival analyses. Therefore, the clinical relevance of this observation should be established conclusively by therapy that targets HER‐2 in a prospective Phase II clinical trial. Cancer 2003;98:66–73. © 2003 American Cancer Society.DOI 10.1002/cncr.11476
Sudden onset of the blastic phase of chronic myelogenous leukemia
Authors: Kantarjian Hagop , O'Brien Susan , Cortes Jorge , Giles Francis , Thomas Deborah , Kornblau Steven , Shan Jianquin , Beth Rios Mary , Keating Michael , Freireich Emil , Talpaz Moshe 
Published: June 2003

AbstractBACKGROUNDTherapeutic options in Philadelphia chromosome‐positive chronic myelogenous leukemia (Ph‐positive CML) in chronic phase include allogeneic stem cell transplantation (SCT) and treatments other than allogeneic SCT. The choice of therapy often depends on the mortality risk of allogeneic SCT. Delaying SCT until the disease demonstrates resistance to other strategies (e.g., imatinib mesylate or interferon‐α) entails the risk of the development of a sudden blastic phase, which may not permit enough time to perform a SCT.METHODSThe current study was performed to define the incidence and patterns of sudden‐onset blastic‐phase CML in relation to the risk inherent in delaying allogeneic SCT. Of a study group of 1286 patients who were referred in early chronic‐phase CML between 1981–2001 and who received therapies other than allogeneic SCT, 1093 patients had regular follow‐up at the study institution. A sudden onset of blastic phase was defined as having its onset within 3 months from a previously documented complete hematologic response.RESULTSAmong the 1093 patients, 183 patients developed blastic‐phase disease, which was of sudden onset in 46 patients (25%; 4% of the total). The incidence of sudden blastic phase was 0.4% in the first year, 1.8% in the second year, and 2.6% in the third year. Patients with sudden blastic‐phase disease were found to have more often low‐risk features at the time of presentation, including low incidences of blasts and thrombocytosis. Sudden blastic‐phase CML was found to be associated with a higher incidence of lymphoid blastic morphology (67% vs. 22%; P < 0.0001), which resulted in a higher response rate to blastic‐phase therapy (70% vs. 29%; P < 0.0001) and significantly longer survival from the onset of blastic‐phase disease (median of 12 months vs. 6 months; P < 0.01). Twenty‐four of the 42 patients with sudden blastic‐phase disease who were treated at the M. D. Anderson Cancer Center were able to undergo allogeneic SCT in second chronic phrase (n = 13) or transformed phase (n = 11); at the time of last follow‐up, 6 patients were alive without evidence of disease at a median of 18 months.CONCLUSIONSThe low rates of sudden blastic transformation in the first 3 years of the course of disease for CML and the salvage rate of these patients with allogeneic SCT should be considered in relation to the transplantation mortality in patients with early chronic‐phase disease and the early promising results with imatinib mesylate therapy. Cancer 2003;98:81–5. © 2003 American Cancer Society.DOI 10.1002/cncr.11477
A Phase I–II trial of polyethylene glycol‐conjugated L‐asparaginase in patients with multiple myeloma
Authors: Agrawal Neeraj R. , Bukowski Ronald M. , Rybicki Lisa A. , Kurtzberg Joanne , Cohen Lewis J. , Hussein Mohamad A. 
Published: June 2003

AbstractBACKGROUNDMultiple myeloma remains an incurable disease. New agents are needed to improve therapy for patients with this disease. Previous investigators evaluated in vitro sensitivity of myeloma cells to polyethylene glycol‐conjugated L‐asparaginase (PEG‐L‐asparaginase) using the human tumor clonogenic assay. Of the 19 myeloma samples evaluated, 63% were inhibited at 0.075 IU/mL, and 74% were inhibited at 0.75 IU/mL. PEG‐L‐asparaginase is a form of Escherichia coli‐derived L‐asparaginase that is bound covalently to polyethylene glycol. Compared with the native form, it has a longer half‐life and is less likely to cause allergic reactions.METHODSThe authors conducted a Phase I–II trial using PEG‐L‐asparaginase as a single agent in patients with recurrent and/or refractory multiple myeloma.RESULTSTwenty‐two patients received a median of two doses of PEG‐L‐asparaginase. In the 17 patients who are evaluable for response, a complete response was observed in one patient after four doses, and stable disease was observed in eight patients. Progression of disease was the reason for termination from study in the remaining eight patients. The median survival was 31.7 months, with four patients who were alive at 72 months after the start of therapy. Grade 3–4 toxicity was noted by the PEG‐L‐asparaginase 2000 mg/m2 level. Severe allergic reactions were noted only at the highest dose level.CONCLUSIONSCurrent data suggest that the maximal tolerated dose for single agent PEG‐L‐asparaginase in relapse/refractory multiple myeloma patients is 1000 mg/m2 every 4 weeks. We could not identify any correlation between dose, plasma level and response. In this advanced group of patients we noted stable disease and/or reponse in 52% of evaluable patients. PEG‐L‐asparaginase has lower tolerance when used in the standard dosage as a single agent in this group of patients. We therefore recommend further studying of PEG‐L‐asparaginase dose of 1000 mg/m2 on alternate weeks with steroids and/or other immune modulators. Cancer 2003;98:94–9. © 2003 American Cancer Society.
Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma
Authors: Pan Hung‐Wei , Ou Yueh‐Hsing , Peng Shian‐Yang , Liu Shu‐Hsian , Lai Po‐Lin , Lee Po‐Hwaung , Sheu Jin‐Chuan , Chen Chi‐Ling , Hsu Hey‐Chi 
Published: June 2003

AbstractBACKGROUNDIntrahepatic metastasis via portal vein spread is an important feature and a crucial unfavorable prognostic factor of hepatocellular carcinoma (HCC). To identify the molecular factors for tumor progression, the authors used differential display (DD) to analyze aberrant gene expression in HCC. The goal of the current study was to elucidate the clinicopathologic and prognostic significance of osteopontin (OPN) in HCC progression.METHODSOPN mRNA levels, which were increased preferentially in HCC in a DD assay and verified with Northern blotting, were measured in 240 surgically removed, unifocal, primary HCCs using the reverse transcription–polymerase chain reaction at the exponential phase. OPN mRNA expression was correlated with clinicopathologic features, particularly portal vein invasion, early tumor recurrence, and prognosis.RESULTSOsteopontin mRNA was overexpressed in 133 tumors (55%). The OPN overexpression was associated closely with α‐fetoprotein elevation (P = 0.001), p53 mutation (P = 0.021), larger tumors (P = 0.002), high‐grade HCC (P < 0.001), late‐stage HCC (P < 0.001), early tumor recurrence and/or metastasis (P = 0.003), and a lower 10‐year survival rate (P = 0.00013). Multivariate analysis revealed that tumor stage and early tumor recurrence were crucial prognostic factors. In early‐stage HCC, which has no vascular invasion and a lower early tumor recurrence than late‐stage HCC, OPN mRNA overexpression predicted a higher early recurrence rate (P = 0.003).CONCLUSIONSOPN mRNA overexpression was correlated closely with high‐grade, late‐stage, and early tumor recurrence, which lead to poorer prognosis. Osteopontin overexpression might serve as an unfavorable prognostic factor and a useful marker for predicting early recurrence in early‐stage HCC. Cancer 2003;98:119–27. © 2003 American Cancer Society.DOI 10.1002/cncr.11487