bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Biological Activity of a Growth Hormone (GH) Mutant (R77C) and Its Impact on GH Responsiveness and Stature
Authors: Petkovic Vibor , Besson Amélie , Thevis Mario , Lochmatter Didier , Eblé Andrée , Flück Christa E. , Mullis Primus E. 
Published: May 2007

AbstractContext and Objective: A single missense mutation in the GH-1 gene converting codon 77 from arginine (R) to cysteine (C) yields a mutant GH-R77C peptide, which was described as natural GH antagonist.Design, Setting, and Patients: Heterozygosity for GH-R77C/wt-GH was identified in a Syrian family. The index patient, a boy, was referred for assessment of his short stature (−2.5 sd score) and partial GH insensitivity was diagnosed. His mother and grandfather were also carrying the same mutation and showed partial GH insensitivity with modest short stature.Interventions and Results: Functional characterization of the GH-R77C was performed through studies of GH receptor binding and activation of Janus kinase 2/Stat5 pathway. No differences in the binding affinity and bioactivity between wt-GH and GH-R77C were found. Similarly, cell viability and proliferation after expression of both GH peptides in AtT-20 cells were identical. Quantitative confocal microscopy analysis revealed no significant difference in the extent of subcellular colocalization between wt-GH and GH-R77C with endoplasmic reticulum, Golgi, or secretory vesicles. Furthermore studies demonstrated a reduced capability of GH-R77C to induce GHR/GHBP gene transcription rate when compared with wt-GH.Conclusion: Reduced GH receptor/GH-binding protein expression might be a possible cause for the partial GH insensitivity with delay in growth and pubertal development found in our patients. In addition, this group of patients deserves further attention because they could represent a distinct clinical entity underlining that an altered GH peptide may also have a direct impact on GHR/GHBP gene expression causing partial GH insensitivity.
Effects of Diet-Induced Moderate Weight Reduction on Intrahepatic and Intramyocellular Triglycerides and Glucose Metabolism in Obese Subjects
Authors: Sato Fumihiko , Tamura Yoshifumi , Watada Hirotaka , Kumashiro Naoki , Igarashi Yasuhiro , Uchino Hiroshi , Maehara Tadayuki , Kyogoku Shinsuke , Sunayama Satoshi , Sato Hiroyuki , Hirose Takahisa , Tanaka Yasushi , Kawamori Ryuzo 
Published: May 2007

Abstract
Context: Although moderate weight reduction is recommended as primary therapy of metabolic syndrome, little information is known regarding metabolic changes associated with moderate weight reduction in nondiabetic obese subjects.
Objective: The aim of this study was to determine the effects of a moderate weight reduction program on intracellular lipid and glucose metabolism in muscle and liver.
Participants: Data for 13 nondiabetic obese subjects were evaluated.
Intervention: Subjects were put on a 3-month mildly hypocaloric diet therapy (∼35 kcal/kg of ideal body weight).
Main Outcome Measures: Intrahepatic lipid (IHL) and intramyocellular lipid were measured by using 1H magnetic resonance spectroscopy. Peripheral insulin sensitivity and splanchnic glucose uptake were evaluated by euglycemic-hyperinsulinemic clamp with oral glucose load.
Results: Diet therapy for 3 months resulted in 6% reduction in body weight (from 99.9 ± 7.3 to 93.8 ± 6.6 kg, P &lt; 0.0001). This change was accompanied by reduction of plasma glucose and insulin excursions during 75-g oral glucose tolerance tests, decrease in diastolic blood pressure, glycated hemoglobin, serum low-density lipoprotein cholesterol, and triglyceride. These changes were also accompanied by a decrease in IHL (from 12.9 to 8.2%, P &lt; 0.01) and increase in splanchnic glucose uptake (from 13.5 to 35.0%, P &lt; 0.03). On the other hand, the diet program did not affect intramyocellular lipid or glucose infusion rate during euglycemic hyperinsulinemic clamp.
Conclusions: Our results suggest that moderate weight reduction in obese subjects decreased IHL and augmented splanchnic glucose uptake. This mechanism is at least in part involved in improvement of glucose metabolism by moderate weight reduction in obese subjects.
Insulin Sensitivity after Metformin Suspension in Normal-Weight Women with Polycystic Ovary Syndrome
Authors: Palomba Stefano , Falbo Angela , Russo Tiziana , Manguso Francesco , Tolino Achille , Zullo Fulvio , De Feo Pierpaolo , Orio Francesco 
Published: May 2007

Abstract
Context: To date, the metabolic effects of the long-term metformin administration in anovulatory patients with polycystic ovary syndrome (PCOS) are known, whereas few data are available on the effects of its suspension.
Objective: The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients.
Design: This was a prospective, randomized, placebo-controlled study.
Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Italy.
Patients: Patients included 30 normal-weight anovulatory PCOS women and 10 age- and body mass index-matched healthy controls.
Intervention: PCOS patients were randomized to receive 1700 mg daily metformin (metformin group) or placebo tables (placebo group) for 12 months, whereas no treatment was administered in healthy women (control group).
Main Outcome Measures: Clinical, endocrine, and metabolic profile and clamp insulin sensitivity index were evaluated at study entry and after 6, 12, 18, and 24 months.
Results: At baseline, the clamp insulin sensitivity index resulted significantly different (P &lt; 0.05) in PCOS patients in comparison with healthy controls, without difference between metformin and placebo groups. During treatment, the clamp insulin sensitivity index was significantly improved (P &lt; 0.05) in the metformin group in comparison with baseline and placebo group, without significant differences between the 6- and 12-month assessments. At 6 and 12 months after treatment suspension, in the metformin group, insulin sensitivity index significantly (P &lt; 0.05) worsened in comparison with that observed at baseline and during treatment and with that observed in the placebo and control groups.
Conclusion: In normal-weight anovulatory PCOS patients, long-term metformin administration exerts beneficial effects on peripheral insulin sensitivity. Furthermore, this effect disappears at treatment suspension.
Determinants of Early Atherosclerosis in Obese Children and Adolescents
Authors: Beauloye Véronique , Zech Francis , Tran Thi Mong Hiep , Clapuyt Philippe , Maes Marc , Brichard Sonia M. 
Published: May 2007

Abstract
Context: Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity.
Objective: The aim of the study was to investigate determinants of increased carotid intima-media thickness (IMT), an early marker of atherosclerosis, in obese children.
Design: A total of 104 obese children [age, 12.7 ± 0.2 yr; body mass index (BMI)-z-score, 2.8 ± 0.7] underwent an oral glucose tolerance test. Fasting levels of glucose, insulin, C-reactive protein and adhesion molecules (sICAM, sVCAM, sE-selectin), lipid profile, adiponectin, and resistin were determined. IMT was measured by ultrasound. Insulin resistance was estimated by the homeostatic model assessment index. Baseline measurements of blood parameters were obtained from 93 nonobese children (age, 13.0 ± 0.2 yr; BMI-z-score, −0.2 ± 0.9), and IMT was measured in 23 other control children with similar characteristics.
Results: Univariate analysis showed a significant positive correlation between IMT and relative BMI, the degree of systolic hypertension, fasting insulin levels, homeostatic model assessment-R index, and resistin concentrations, whereas an inverse correlation with adiponectin levels was found. No correlation was obtained between IMT and classical CV risk factors such as positive familial history of type 2 diabetes or precocious CV disease, visceral obesity, or the lipid profile. C-reactive protein and adhesion molecule levels were not associated with IMT in our obese population. When controlled for sex, Tanner stage, and relative BMI, only adiponectin levels remained an independent determinant of IMT.
Conclusion: Adiponectin more than conventional CV risk factors and inflammation status may be related to early atherosclerosis in obese children.
Modafinil Augmentation for Residual Symptoms of Fatigue in Patients with a Partial Response to Antidepressants
Authors: Lam Jenny Y , Freeman Maisha Kelly , Cates Marshall E 
Published: May 2007

OBJECTIVE: To evaluate the literature discussing the use of modafinil in the treatment of residual symptoms of fatigue in patients with depression. DATA SOURCES: PubMed (1966–March 2007) and International Pharmaceutical Abstracts(1970–March 2007) were searched using the key words modafinil and depression. A manual search of the reference section of the articles retrieved was conducted to identify articles not indexed in either of these sources. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated. Studies were included if modafinil was used to treat patients with residual fatigue from depression and the effects were measured with validated fatigue subscales. DATA SYNTHESIS: One retrospective study, 5 open-label trials, and 2 randomized controlled clinical trials met the inclusion criteria for assessment of residual symptoms of fatigue as assessed by commonly used fatigue subscales after modafinil administration. Although improvement with fatigue has occurred with modafinil therapy, literature regarding the topic is limited by the lack of well-controlled clinical trials. Modafinil does appear to improve residual fatigue with depression as evidenced by open-label trials; however, the efficacy of this agent has not been duplicated in randomized controlled trials. The open-label trials that have been conducted often had no comparator and a small number of patients. In addition, outcome measures used in the studies were not consistent between trials. Modafinil appears to be well tolerated, with the main adverse effects being headache and nausea. CONCLUSIONS: Open-label trials indicate that modafinil may be effective in ameliorating fatigue associated with depression; however, this effect has not been reproduced in randomized, double-blind, placebo-controlled clinical trials. Therefore, the use of modafinil for the treatment of residual fatigue is not recommended due to the lack of reproducible data of its efficacy. Long-term, adequately powered clinical trials should be conducted to determine its place in therapy.
Tigecycline: A Novel Broad-Spectrum Antimicrobial
Authors: Slover Christine M , Rodvold Keith A , Danziger Larry H 
Published: May 2007

OBJECTIVE: To review the literature on tigecycline, a novel antibiotic. DATA SOURCES: References were identified through MEDLINE (1966–February 2007) and International Pharmaceutical Abstracts(1970–February 2007) databases, using the key words tigecycline, glycylcycline, complicated skin and skin structure infections (cSSSI), complicated intraabdominal infections (cIAI), and in vitro. Additional articles for this review were identified by reviewing the bibliographies of articles cited. The package insert was also used as a reference. STUDY SELECTION AND DATA EXTRACTION: In vitro, clinical, and pharmacokinetic studies evaluating tigecycline's safety and efficacy were selected. DATA SYNTHESIS: A tigecycline 100 mg intravenous loading dose followed by an intravenous infusion of 50 mg every 12 hours was shown in clinical trials to be as effective as comparator antibiotics in treating cSSSI and cIAI. Tigecycline has a broad spectrum of activity that includes many resistant bacteria with few treatment options, such as methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase—producing bacteria such as Escherichia coli and Klebsiella pneumoniae. In cSSSI studies, tigecycline was found to be noninferior to vancomycin plus aztreonam with test-of-cure rates of 86.5% and 88.6%, respectively. Tigecycline was also found to be noninferior to imipenem/ cilastatin in cIAI studies; clinical cure rates were 86.1% and 86.2%, respectively. In vitro activity has been demonstrated against other multidrug-resistant microorganisms of concern, such as Acinetobacterspp. Although it has a broad spectrum of activity, tigecycline has inadequate activity against Pseudomonasspp. Nausea and vomiting were the most frequently reported adverse effects. CONCLUSIONS: Tigecycline is approved for the treatment of cSSSI and cIAI infections. To date, little resistance to tigecycline has been reported; however, with widespread use of the drug, resistance will likely occur. Since published studies have not dealt with seriously ill patients, it is recommended that, until further studies have been completed, other agents be used in the treatment of these patients unless no option other than tigecycline exists.
Corticosteroid Treatment of Severe Community-Acquired Pneumonia
Authors: Gorman Sean K , Slavik Richard S , Marin Judith 
Published: May 2007

Objective: To assess the evidence for adjunctive corticosteroids for severe community-acquired pneumonia (CAP). Data Sources: MEDLINE (1966–February 2007) and EMBASE (1980–February 2007) were searched to identify English- and French-language publications that evaluated the use of corticosteroids for CAP in adults. Major search terms included community-acquired pneumonia, intensive care unit, steroids, glucocorticoids, and adrenal cortex hormones. Study Selection and Data Extraction: Clinical studies that evaluated the use of corticosteroids for CAP in adults were included. Clinical and surrogate markers of pneumonia were evaluated. Data Synthesis: Severe CAP is associated with an increase in pulmonary and circulatory cytokines such as interleukin-6 and tumor necrosis factor-α that may be associated with higher mortality. Corticosteroids suppress inflammatory reactions and prevent migration of inflammatory cells from the circulation to tissues by suppressing the synthesis of chemokines and cytokines. One observational comparative study and 2 randomized, controlled studies examined the effects of corticosteroid therapy at various doses on endpoints of pulmonary and systemic inflammation and clinical outcomes. One small observational pilot study revealed that methylprednisolone blunted some of the pulmonary and systemic markers of inflammation. One small, randomized, placebo-controlled study revealed that hydrocortisone had no significant effects on markers of pulmonary and systemic inflammation or clinical outcomes. Another small, randomized, placebo-controlled preliminary study with methodological limitations revealed improvements in oxygenation, organ dysfunction score, and markers of inflammation favoring hydrocortisone over placebo. Conclusions: Given the lack of proven benefit on clinically meaningful endpoints and adverse events, corticosteroids cannot be recommended for adjunctive treatment of severe CAP.
Outcome of cognitive‐behavioural therapy in training practice with anxiety disorder patients
Authors: Bados Arturo , Balaguer Gemma , Saldaña Carmina 
Published: May 2007

Objectives This study aims to assess the effectiveness of cognitive‐behavioural therapy applied by trainee therapists in patients with anxiety disorders seen in a private university service and to examine whether this effectiveness is comparable to that observed in controlled studies.Design We compared the effectiveness of cognitive‐behavioural therapy at a private centre with that observed in meta‐analyses and reviews of controlled studies.Methods Out of the 96 initial patients with anxiety disorder, 64 completed the cognitive‐behavioural treatment and 59 also answered a series of questionnaires pre‐ and post‐treatment. The effect size of the intervention was calculated, as were the percentages of patients who improved and those who recovered.Results The pre‐post effect size (1.09) was large, although somewhat lower than those observed in a meta‐analysis of Spanish studies and in a range of international meta‐analyses; moreover, twice as many hours of treatment were administered (M=27.4) and the drop‐out rate was higher (33.3%). The percentages of patients who improved (61%) and those who recovered (52.5%) were roughly comparable to those reported in various reviews of studies performed in anxiety disorders.Conclusions Cognitive‐behavioural therapy applied by trainee therapists in a private university service appears effective, although this efficacy may be somewhat lower than that in controlled studies. Moreover, the duration of treatment and the drop‐out rate may be higher.
Heavenly Khao Chae——Aromatic Soaked Rice
Authors: yu su-mei 
Published: May 2007

Khao chae--aromatic soaked rice--is served only during the hot summer months in Thailand. Its exquisite taste and laborious preparation beckoned the author, Su-Mei Yu, back to her birthplace. Skilled elderly cooks recruited by friends abruptly changed their minds about sharing their methods. These refusals led to an understanding of their superstitious beliefs.
With those who believe otherwise, the author not only learned how to make several versions of khao chae, but their shared memories taught her the dish's history and its influence on the people who make and eat it. Its ancient tradition binds together the people of a displaced nation, the Mon, among whom khao chae originated. Their ancient New Year custom, adopted by the Thais, became a summer food tradition in the Royal court of King Chulalongkhorn (1868-1910), one of the most celebrated times for Thai culinary art. The court turned the cooking of khao chae into a competitive feat. Although more than a century has passed, and despite climatic change and westernization of Thai culture, the remembrances of magical feasts of khao chae floated back as the summer heat stirred the minds of elderly folks.
Lactose Intolerance and Evolution: No Use Crying Over Undigested Milk
Authors: scheindlin benjamin 
Published: May 2007

Lactose intolerance is an inability to digest milk sugar, characterized by abdominal cramps, nausea, and diarrhea after ingesting milk products. It develops in adolescence or adulthood among those whose bodies naturally stop producing the lactose-digesting enzyme lactase after childhood. Although uncommon in the United States, lactose intolerance actually occurs in the majority of people around the world. The ability to continue producing lactase, and thus to digest milk products, is a relatively recent evolutionary development.
After presentation of an illustrative clinical example, the biology of lactase production and lactose intolerance is reviewed. The "culture-historical" hypothesis of Simoons in the 1970's held that persistent lactase production developed in a dairy herding population in Northern Europe during a time of food scarcity, when the ability to digest milk would have provided a survival advantage. Simoons demonstrated that low prevalence of lactose intolerance was associated with pastoral practices among early populations around the world.
Hirschhorn recently provided strong genetic evidence for the culture-historical hypothesis using contemporary techniques of genomics and single nucleotide polymorphisms. His research group found that European derived persistent lactase production is due to a mutation near the lactase gene that occurred only about 10 million years ago and rapidly increased in prevalence.
Multi-Institutional Phase II Study of S-1 Monotherapy in Advanced Gastric Cancer with Pharmacokinetic and Pharmacogenomic Evaluations
Authors: Jeung Hei-Cheul , Rha Sun Young , Kim Hoon Kyo , Lim Ho Young , Kim Samyong , Kim Si Young , Gong Soo Jeong , Park Chan Hee , Ahn Joong Bae , Noh Sung Hoon , Chung Hyun Cheol 
Published: May 2007

Abstract
This study describes the first phase II study of S-1, a novel oral fluoropyrimidine, in a non-Japanese Asian population with advanced gastric cancer. S-1 was administered twice daily for 28 days every 6 weeks. A pharmacokinetic study was performed on day 28 of cycles 1 and 3. Genomic DNA from peripheral mononuclear cells was analyzed using a cDNA microarray-based comparative genomic hybridization (CGH) method. Thirty-one patients were initially given a dose of 35 mg/m2 twice daily (bid) (group 1); then, the protocol was amended by increasing the dose to 40 mg/m2 bid for an additional 31 patients (group 2) because of good tolerability to S-1. The overall response rate was 19.3% (95% confidence interval, 9.2%–29.5%). Over a median follow-up duration of 265 days, the median time to progression and overall survival time were 126 and 264 days, respectively. The 1-year survival rate was 34%. There was no grade 4 toxicity and the major adverse event was anemia. Pharmacokinetic parameters were similar to those of the previous Japanese reports. Microarray CGH identified 18 genes with copy number changes that were associated with hemoglobin reduction with S-1 treatment. A logistic regression analysis, integrating one clinical parameter (initial hemoglobin level) combined with three genetic copy number variations (HIST1H2BL, C10orf127, and XPNPEP2), provided a predictive model for the development of severe hemoglobin reduction. In conclusion, this study showed the feasibility of using S-1 at 35 mg/m2 bid in gastric cancer. We suggest that the pharmacogenomic markers identified in this study may be potential candidates for predicting anemia after S-1 treatment.
Intensity-Modulated Radiation Therapy for Head and Neck Carcinoma
Authors: Grégoire Vincent , De Neve Wilfried , Eisbruch Avraham , Lee Nancy , Van den Weyngaert Danielle , Van Gestel Dirk 
Published: May 2007

Learning Objectives
After completing this course, the reader will be able to: Outline innovations related to targeted radiation therapy.Describe trials proving an advantage using IMRT.Assess treatment planning modalities and how IMRT fields are designed.Evaluate when there is a toxicity advantage for IMRT.Discern when conventional radiotherapy should be used instead of IMRT.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Primary Effusion Lymphoma
Authors: Chen Yi-Bin , Rahemtullah Aliyah , Hochberg Ephraim 
Published: May 2007

Abstract
Primary effusion lymphoma (PEL) is a rare HIV-associated non-Hodgkin's lymphoma (NHL) that accounts for approximately 4% of all HIV-associated NHL. PEL has a unique clinical presentation in having a predilection for arising in body cavities such as the pleural space, pericardium, and peritoneum. PEL cells are morphologically variable with a null lymphocyte immunophenotype and evidence of human herpesvirus (HHV)-8 infection. The exact oncogenic mechanisms of HHV-8 have not been clearly defined. Treatment is usually with combination CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and antiretroviral therapy (if HIV positive). The prognosis for PEL is poor, with a median survival time of around 6 months. As the exact molecular steps in HHV-8–driven oncogenesis are unraveled, it is hoped that more specific therapeutic targets will be revealed.