bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart Rate Variability in Emergency Department Patients with Sepsis
Authors: Barnaby Douglas , Ferrick Kevin , Kaplan Daniel T. , Shah Sachin , Bijur Polly , Gallagher E. John 
Published: October 2002

Abstract Objective: To test the hypothesis that heart rate variability (HRV) can provide an early indication of illness severity among patients presenting to the emergency department (ED) with sepsis. Methods: The authors enrolled a convenience sample of 15 ED patients meeting the American College of Chest Physicians/Society of Critical Care Medicine criteria for sepsis. Each patient had continuous Holter monitoring performed in the ED. Acute Physiology and Chronic Health II (APACHE II) and Sequential Organ Failure (SOFA) scores were calculated for the day of presentation. Holter tapes obtained in the ED were analyzed off‐line to calculate HRV variables for the 5‐minute segment with the least artifact and non‐sinus beats. These variables were correlated with APACHE II and SOFA scores. Results: LFnu (normalized low‐frequency power), an assessment of the relative sympathetic contribution to overall HRV, was correlated with increased illness severity as calculated using APACHE II (r = ‐0.67, r2= 0.43) and SOFA (r = ‐0.80, r2= 0.64) scores. LF/HF ratio (low‐frequency/high‐frequency ratio), a measure of sympathovagal balance, was correlated with the SOFA score [r = ‐0.54 (95% CI = ‐0.83 to ‐0.01), r2= 0.29]. All five patients who required critical care monitoring or ventilatory support or who died during the first 5 days of their hospitalization had LFnu values below 0.5 and LF/HF ratios less than 1.0. None of the patients with measurements greater than these threshold values died or required these interventions during the five days following admission. Conclusions: A single variable, LFnu, which reflects sympathetic modulation of heart rate, accounted for 40‐60% of the variance in illness severity scores among patients presenting to the ED with sepsis. HRV, as reflected in LFnu and the LF/HF ratio and measured with a single brief (5‐minute) period of monitoring while in the ED, may provide the emergency physician with a readily available, noninvasive, early marker of illness severity. The threshold effect of LFnu and LF/HF in the prediction of early clinical deterioration was an unexpected finding and should be regarded as hypothesis‐generating, pending further study.
Gamma Hydroxybutyric Acid (GHB) Intoxication
Authors: Mason Phillip E. , Kerns William P. 
Published: October 2002

AbstractGamma hydroxybutyric acid (GHB) is a naturally occurring analog of gamma‐aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. In the past decade it has become very popular as a dietary supplement and recreational drug. Acute overdose leads to profound alteration of mental status and variable amounts of respiratory depression. With proper management, most patients recover fully within six hours. However, respiratory arrest and death have been reported in severe GHB intoxication. In addition to acute overdose, there is a GHB withdrawal syndrome that is similar to sedative/hypnotic and ethanol withdrawal. Recently several congeners of GHB, gamma butyrolactone and 1,4‐butanediol, have emerged as drugs of abuse and show toxidromes similar to GHB. Emergency physicians should be familiar with the presentation and management of GHB‐related emergencies.
Hepatocellular Carcinoma in Children and Adolescents: Results From the Pediatric Oncology Group and the Children’s Cancer Group Intergroup Study
Authors: Katzenstein Howard M. , Krailo Mark D. , Malogolowkin Marcio H. , Ortega Jorge A. , Liu-Mares Wen , Douglass Edwin C. , Feusner James H. , Reynolds Marleta , Quinn John J. , Newman Kurt , Finegold Milton J. , Haas Joel E. , Sensel Martha G. , Castleberry Robert P. , Bowman Laura C. 
Published: October 2002

PURPOSE: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B). PATIENTS AND METHODS: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children’s Cancer Group (CCG) 8881). After initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or regimen B (n = 26). RESULTS: For the entire cohort, the 5-year EFS estimate was 19% (SD = 6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD = 12%), 8% (SD = 5%), and 0%, respectively. Five-year EFS estimates were 20% (SD = 9%) and 19% (SD = 8%) for patients on regimens A and B, respectively (P = .78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for regimen B when compared with regimen A. Outcome was similar for either regimen within disease stages. Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy. CONCLUSION: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was uniformly poor for children with advanced-stage disease treated with either regimen. New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.
Decision-Analytic Model and Cost-Effectiveness Evaluation of Postmastectomy Radiation Therapy in High-Risk Premenopausal Breast Cancer Patients
Authors: Lee Jason H. , Glick Henry A. , Hayman James A. , Solin Lawrence J. 
Published: October 2002

PURPOSE: To present a decision model that describes the clinical and economic outcomes of node-positive breast cancer with and without postmastectomy radiation therapy (PMRT). METHODS: A Markov process was constructed to project the natural history of breast cancer following mastectomy in premenopausal node-positive women. Biannual hazards of local and distant recurrence without PMRT were derived from a large meta-analysis of adjuvant systemic therapy trials for breast cancer. The addition of PMRT reduced the risk of disease relapse by an odds ratio of 0.69. Costs of PMRT ($11,600) and recurrent breast cancer ($4,250 to 16,200/year) were estimated from available literature. The model projected number of recurrences, relapse-free and overall survival, and costs to 15 years, using a discount rate of 3%. Cost-effectiveness ratios were calculated per incremental year of life and quality-adjusted year of life gained. One- and two-way sensitivity analyses were performed to determine the sensitivity of results to clinical and economic assumptions. RESULTS: The model projected 15-year relapse-free survival of 52% and 43% with and without PMRT, respectively. Overall survival was increased from 48% to 55% with PMRT, resulting in an incremental 0.29 years of life gained per subject. PMRT increased 15-year costs from $40,800 to $48,100. Cost per year of life gained was $24,900, or $22,600 when survival was adjusted for quality of life. Results of the model were relatively sensitive to radiation therapy cost and breast cancer relapse risk. CONCLUSION: This analysis suggests that PMRT offers substantial clinical benefits achieved in a cost-effective manner, with an average cost per year of life gained of $24,900. Results of the model were robust under a wide range of clinical and economic parameters.
Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91
Authors: Perel Yves , Auvrignon Anne , Leblanc Thierry , Vannier Jean-Pierre , Michel Gerard , Nelken Brigitte , Gandemer Virginie , Schmitt Claudine , Lamagnere Jean-Pierre , De Lumley Lionel , Bader-Meunier Brigitte , Couillaud Gerard , Schaison Gerard , Landman-Parker Judith , Thuret Isabelle , Dalle Jean-Hugues , Baruchel Andre , Leverger for the Guy ,   Group LAME of the French Society of Pediatric Hematology and Immunology
Published: October 2002

PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% ± 6% and 48% ± 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% ± 19% v 50% ± 15%; P = .25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% ± 13% v 58% ± 15%; P = .04) due to a higher salvage rate after relapse. CONCLUSION: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.
Outcomes of Growth Hormone Replacement Therapy in Survivors of Childhood Acute Lymphoblastic Leukemia
Authors: Leung Wing , Rose Susan R. , Zhou Yinmei , Hancock Michael L. , Burstein Stephen , Schriock Elizabeth A. , Lustig Robert , Danish Robert K. , Evans William E. , Hudson Melissa M. , Pui Ching-Hon 
Published: October 2002

PURPOSE: Little is known about the long-term efficacy or adverse effects of growth hormone (GH) replacement therapy in survivors of childhood acute lymphoblastic leukemia (ALL) who have GH deficiency. We investigated the adult height of patients who had received GH and estimated their risk of leukemia relapse or development of a second malignancy. PATIENTS AND METHODS: Of 910 patients treated for ALL at a single institution, 47 had received GH replacement therapy. The linear growth of these 47 patients was retrospectively evaluated. Their risk of leukemia relapse or second malignancy was compared with that of survivors who did not undergo GH therapy. RESULTS: The median height SD score at the start of GH therapy had decreased by 1.0 since the time of diagnosis of ALL. After a median duration of 4.5 years of GH therapy, adult height SD scores improved and approached height SD scores at the time of diagnosis of ALL. The median adult height for male patients was 173.2 cm (range, 157 to 191.9 cm), and for female patients, it was 158.1 cm (range, 141 to 168 cm). None of the patients developed adverse effects requiring discontinuation of GH treatment. At the 7-year and 11-year landmarks in continuous hematologic remission, there was no statistical evidence that GH therapy was associated with leukemia relapse or development of a second malignancy. CONCLUSION: This study suggests that GH replacement therapy is safe and efficacious for the correction of GH deficiency in survivors of childhood ALL.
Comparative Detection of Lymph Node Micrometastases of Stage II Colorectal Cancer by Reverse Transcriptase Polymerase Chain Reaction and Immunohistochemistry
Authors: Noura Shingo , Yamamoto Hirofumi , Ohnishi Tadashi , Masuda Norikazu , Matsumoto Takashi , Takayama Osamu , Fukunaga Hiroki , Miyake Yasuhiro , Ikenaga Masakazu , Ikeda Masataka , Sekimoto Mitsugu , Matsuura Nariaki , Monden Morito 
Published: October 2002

PURPOSE: Inconsistent conclusions have been drawn about the clinical significance of micrometastases in lymph nodes (LNs) of node-negative colorectal cancer (CRC) patients. We performed a comparative study of detection of micrometastases using immunohistochemistry (IHC) by anti-cytokeratin antibody and carcinoembryonic antigen (CEA)-specific reverse-transcriptase polymerase chain reaction (RT-PCR) in the same patients, in an attempt to move closer to their clinical application. PATIENTS AND METHODS: Sixty-four CRC patients, with RNA of good quality available from paraffin-embedded LN specimens, were selected from 84 stage II patients who underwent curative surgery between 1988 and 1996. We investigated associations between the presence of micrometastases by each method and prognosis. RESULTS: Micrometastases were detected in 19 (29.6%) of 64 patients by RT-PCR and in 35 (54.7%) of 64 patients by IHC. By RT-PCR analysis, patients exhibiting a positive band for CEA mRNA had a significantly worse prognosis than those who were RT-PCR–negative, with respect to both disease-free and overall survival (P = .027 and .015, respectively). By IHC analysis, the presence of micrometastasis did not predict patient outcome in terms of either disease-free or overall survival. Infiltrating pattern of tumor growth characteristic was significantly associated with shorter disease-free survival among various clinical or pathologic factors. By multivariate Cox regression analysis, micrometastasis detected by RT-PCR and the Crohn’s-like lymphoid reaction were both independent prognostic factors. CONCLUSION: Micrometastases detected by RT-PCR, but not IHC, may be of clinical value in identifying patients who may be at high risk for recurrence of CRC and who are therefore likely to benefit from systemic adjuvant therapy.
Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases With a Proposal for Low-Grade and Intermediate-Grade Groups
Authors: Hochwald Steven N. , Zee Sui , Conlon Kevin C. , Colleoni Roberto , Louie Otway , Brennan Murray F. , Klimstra David S. 
Published: October 2002

PURPOSE: In some organs (eg, the lung), endocrine tumors are classified on the basis of mitotic rate and necrosis. The purpose of this study was to evaluate prognostic factors in pancreatic endocrine neoplasms recently treated at a single institution. PATIENTS AND METHODS: In 136 patients undergoing surgery from 1979 to 1998, the influence on disease-free survival (DFS) and disease-specific survival (DSS) of tumor size, mitotic rate, vascular invasion, necrosis, metastases, and nuclear grade was determined. Cases were further grouped according to an existing proposed classification system and then regrouped on the basis of mitotic rate (< 2 mitoses per 50 high-power fields v higher) and necrosis (present or absent) into low- and intermediate-grade groups. RESULTS: Correlations with DFS and DSS in univariate analysis included ≤ 2 mitoses per 50 high-power fields (P = .001, P = .002), vascular invasion (P = .02, P = .04), size ≤ 2 cm (P = .01, P = .05), metastases (P = .0002, P = .07), necrosis (P = .002, P = .16), and nuclear grade (P = .04, P = .33), respectively. By multivariate analysis, for DFS, tumor necrosis and presence of metastases retained significance (P = .01, P = .04, respectively). For DSS, only mitotic rate was a prognostic factor (P = .02). Among the 18 macroadenomas, eight borderline tumors, and 48 low-grade carcinomas, there was no significant difference in DSS between any groups (P = .3). However, in evaluating our newly proposed groups, the differences in DFS and DSS between low- and intermediate-grade groups were highly significant (P = .0007, P = .006, respectively). CONCLUSION: Pancreatic endocrine neoplasms exhibit a spectrum of biologic behavior, and the proposed benign (macroadenoma) and borderline groups contain potentially aggressive tumors. An alternative system based on mitotic rate and necrosis correlates strongly with survival without specifically designating any group as benign.
Phase II Study of Anti–Gastrin-17 Antibodies, Raised to G17DT, in Advanced Pancreatic Cancer
Authors: Brett B. T. , Smith S. C. , Bouvier C. V. , Michaeli D. , Hochhauser D. , Davidson B. R. , Kurzawinski T. R. , Watkinson A. F. , Van Someren N. , Pounder R. E. , Caplin M. E. 
Published: October 2002

PURPOSE: The prognosis for advanced pancreatic cancer remains poor. Gastrin acts as a growth factor for pancreatic cancer. We describe the first study of the antigastrin immunogen G17DT in pancreatic cancer. Our aims were to determine the antibody response, safety, tolerability, and preliminary evidence of efficacy of G17DT in advanced pancreatic cancer. PATIENTS AND METHODS: Thirty patients with advanced pancreatic cancer were immunized with three doses of either 100 μg or 250 μg of G17DT. RESULTS: In the whole group, 20 (67%) of 30 patients produced an antibody response. The 250-μg dose resulted in a significantly greater response rate of 82% compared with 46% for the 100-μg group (P = .018). The most significant side effects, seen in three patients, were local abscess and/or fever. The median survival for the whole group from the date of the first immunization was 187 days; median survival was 217 days for the antibody responders and 121 days for the antibody nonresponders. The difference in survival between the antibody responders and nonresponders was significant (P = .0023). CONCLUSION: Patients with advanced pancreatic cancer are able to mount an adequate antibody response to G17DT. The 250-μg dose is superior to the 100-μg dose, and it appears to be generally well tolerated. Antibody responders demonstrate significantly greater survival than antibody nonresponders. Phase III studies are currently underway in order to determine efficacy.
Increased Oral Bioavailability of Topotecan in Combination With the Breast Cancer Resistance Protein and P-Glycoprotein Inhibitor GF120918
Authors: Kruijtzer C. M.F. , Beijnen J. H. , Rosing H. , ten Bokkel Huinink W. W. , Schot M. , Jewell R. C. , Paul E. M. , Schellens J. H.M. 
Published: October 2002

PURPOSE: We discovered that breast cancer resistance protein (BCRP), a recently identified adenosine triphosphate–binding cassette drug transporter, substantially limits the oral bioavailability of topotecan in mdr1a/1b(−/−) P-glycoprotein (P-gp) knockout and wild-type mice. GF120918 is a potent inhibitor of BCRP and P-gp. The aim was to increase the bioavailability of topotecan by GF120918. PATIENTS AND METHODS: In cohort A, eight patients received 1.0 mg/m2 oral topotecan with or without coadministration of one single oral dose of 1,000 mg GF120918 (day 1 or day 8). In cohort B, eight other patients received 1.0 mg/m2 intravenous topotecan with or without 1,000 mg oral GF120918 to study the effect of GF120918 on the systemic clearance of topotecan. RESULTS: After oral topotecan, the mean area under the plasma concentration-time curve (AUC) of total topotecan increased significantly from 32.4 ± 9.6 μg·h/L without GF120918 to 78.7 ± 20.6 μg·h/L when GF120918 was coadministered (P = .008). The mean maximum plasma concentration of total topotecan increased from 4.1 ± 1.5 μg/L without GF120918 to 11.5 ± 2.4 μg/L with GF120918 (P = .008). The apparent bioavailability in this cohort increased significantly from 40.0% (range, 32% to 47%) to 97.1% (range, 91% to 120%) (P = .008). Interpatient variability of the apparent bioavailability was 17% without and 11% with GF120918. After intravenous administration of topotecan, coadministration of oral GF120918 had a small but statistically significant effect on the AUC and systemic clearance of total topotecan but no statistically significant effect on maximum plasma concentration and terminal half-life of total topotecan. CONCLUSION: Coadministration of the BCRP and P-gp inhibitor GF120918 resulted in a significant increase of the systemic exposure of oral topotecan. The apparent oral bioavailability increased from 40.0% without to 97.1% with GF120918.
Pharmacobiologically Based Scheduling of Capecitabine and Docetaxel Results in Antitumor Activity in Resistant Human Malignancies
Authors: Nadella Padma , Shapiro Charles , Otterson Gregory A. , Hauger Marsha , Erdal Selnur , Kraut Eric , Clinton Steven , Shah Manisha , Stanek Mike , Monk Paul , Villalona-Calero Miguel A. 
Published: October 2002

PURPOSE: Capecitabine and docetaxel have demonstrated preclinical antitumor synergy. This synergy is thought to occur from docetaxel-mediated upregulation of thymidine phosphorylase (dThdPase), an enzyme responsible for the relative tumor selectivity of capecitabine. On the basis of the time-dependency and transiency for this upregulation, we performed a phase I study of capecitabine in combination with weekly docetaxel. We hypothesized that weekly docetaxel would result in sustained dThdPase expression and that capecitabine administration at times of maximum dThdPase upregulation would increase the therapeutic index for this combination. PATIENTS AND METHODS: Patients with advanced solid malignancies received docetaxel on days 1, 8, and 15, and capecitabine bid on days 5 to 18, every 4 weeks. Docetaxel was fixed at 36 mg/m2/wk, whereas capecitabine was escalated in successive patients cohorts. RESULTS: Sixteen patients received 77 courses at capecitabine doses from 950 to 1,500 mg/m2/d. The most common toxicities were hand-foot syndrome, diarrhea, nausea/vomiting, and asthenia. Grades 3 to 4 hematologic toxicities were infrequent and no treatment-related hospitalizations occurred. Three of three patients treated at 1,500/36 mg/m2 capecitabine/docetaxel developed grade 3 hand-foot syndrome or diarrhea during either their first or second course, whereas only two of 13 patients at 1,250/36 mg/m2 doses developed significant toxicity. Antitumor responses (n = 7) occurred in patients with hepatocellular, non–small-cell lung, and chemotherapy-refractory breast, bladder, and colorectal carcinomas. Prolonged stabilizations occurred in patients with metastatic mesothelioma (n = 2), chemorefractory non–small-cell lung carcinoma, and bronchioloalveolar carcinoma. CONCLUSION: Capecitabine in combination with weekly docetaxel is well tolerated. Recommended doses are capecitabine 1,250 mg/m2/d (625 mg/m2 bid) with docetaxel 36 mg/m2/wk. The acceptable toxicity profile in this dose schedule, and the antitumor activity observed, warrant further evaluation of this regimen.
Spasmolytic effects of Baccharis conferta and some of its constituents
Authors: Weimann C , Göransson U , Pongprayoon-Claeson U , Claeson P , Bohlin L , Rimpler H , Heinrich M 
Published: October 2002

Abstract
The Nahua of the Mexican state of Veracruz use Baccharis conferta in the treatment of a variety of gastrointestinal illnesses, especially diarrhoea associated with gastrointestinal cramps. The aerial parts of B. conferta were investigated phytochemically and pharmacologically using the guinea pig ileum assay as a model (histamine, KCl and electric stimulation). The crude ethanolic extract showed a dose-dependent antispasmodic effect that was particularly strong in flavonoid-rich fractions (e.g. IC50 value for fraction E.3.1 from the ethyl acetate fraction, in histamine-induced contraction, 10 μg mL−1). Several flavonoids (apigenin-4′,7-dimethylether, naringenin-4,7-dimethylether, pectolinarigenin and cirsimaritin) were isolated, while others were identified in complex fractions by GC-MS. The flavonoids play an important role in the antispasmodic activity of this indigenous drug. Additionally, oleanolic acid and its methyl ester as well as erythrodiol were isolated. Oleanolic acid methyl ester shows weak antibacterial activity against M. luteus and E. coli (20 μg/spot in a TLC assay). The phytochemical as well as the pharmacological data provide some in-vitro evidence for the use of B. conferta in the treatment of gastrointestinal cramps.