bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended‐ and Continuous‐Cycle Oral Contraceptives
Authors: Shrader Sarah P. , Dickerson Lori M.
Published: July 2008

Five new oral contraceptives, classified as extended‐ or continuous‐cycle oral contraceptives, have been approved by the United States Food and Drug Administration. These agents have various combinations of estrogen and progestin, and different effects on the length of women's menstrual cycles. Usually they shorten the duration of menses, decrease the frequency of menses to 4 times/year, or completely eliminate menses. These new oral contraceptives are given in the following regimens: 24 days followed by placebo for 4 days (24/4), 84 days followed by placebo for 7 days (84/7), or continuously (without placebo). These agents contain ethinyl estradiol 20 μg‐drospirenone 3 mg (24/4); ethinyl estradiol 20 μg‐norethindrone 1 mg (24/4); ethinyl estradiol 30 μg‐levonorgestrel 150 μg (84/7); ethinyl estradiol 30 μg‐levonorgestrel 150 μg (84/7) with very low‐dose ethinyl estradiol (10 μg/day) for 7 days; and ethinyl estradiol 20 μg‐levonorgestrel 90 μg continuously. Clinical trials have demonstrated that extended‐ and continuous‐cycle oral contraceptives are as effective in preventing pregnancy as traditional oral contraceptives. These new agents also have similar adverse effects; however, the only significantly different adverse effect compared with traditional oral contraceptives in clinical trials was change in bleeding pattern. These oral contraceptives are associated with more breakthrough bleeding and spotting than the traditional pills. Long‐term effects on efficacy and safety are not known, as these new products generally have been used for only 1–2 years. Extended‐ and continuous‐cycle oral contraceptives are a new option for women desiring decreased menses or for whom decreased menses may alleviate symptoms of coexisting medical conditions.
Key Articles and Guidelines in the Management of Hypertension: 2008 Update
Authors: Gaffney Sarah M. , de Denus Simon , Olson Kari L. , Ripley Toni L. , Robinette Bryan , Summers Kelly M. , Spencer Anne P.
Published: July 2008

Hypertension remains a major risk factor for cardiovascular disease. The optimal choice of pharmacologic and nonpharmacologic treatment regimens is based on a plethora of published literature. This compilation is the initial update to the Key Articles and Guidelines in the Management of Hypertension authored by members of the Cardiology Practice and Research Network of the American College of Clinical Pharmacy, which appeared in Pharmacotherapy in 2004. We present synopses of clinical trials, meta‐analyses, clinical practice guidelines, and other pertinent literature published between May 2003 and June 2007.
Cesium‐Induced QT‐Interval Prolongation in an Adolescent
Authors: O'Brien Catherine E. , Harik Nada , James Laura P. , Seib Paul M. , Stowe Cindy D.
Published: July 2008

Alternative medicine is becoming increasingly popular, especially with terminally ill patients. Most alternative remedies have not been adequately studied or proven effective for the diseases for which they are promoted. In the worst cases, these therapies are harmful. We describe a 16‐year‐old girl with metastatic hepatocellular carcinoma who experienced cesium‐induced QT‐interval prolongation after the start of a cesium chloride‐based alternative treatment regimen. She had received seven courses of chemotherapy, with a cumulative doxorubicin dose of 500 mg/m2 over 5 months, resulting in minimal tumor regression. Against the advice of her oncologist, she abandoned traditional therapy and started an alternative regimen that included cesium chloride supplements. Two weeks later, the patient went to a local emergency department after experiencing two brief syncopal episodes. An electrocardiogram revealed occasional premature ventricular contractions, a QTc interval of 683 msec (normal range for females 450–460 msec), and R on T phenomenon. She was admitted to the hospital and later experienced monomorphic ventricular tachycardia, which resolved spontaneously. Lidocaine therapy was started, and the patient was transferred to a cardiac intensive care unit at our hospital. Her plasma cesium level was 2400 μg/dl (normal <1 μg/dl), and her family was told to stop her alternative treatment regimen. On hospital day 5, as no additional arrhythmias had occurred, lidocaine was discontinued. Two days later, the patient's QTc interval had decreased to 546 msec, and she was discharged home. Two months later, at a follow‐up visit, her serum cesium level was 1800 μg/dl, and her QTc interval was 494 msec. According to the Naranjo adverse drug reaction probability scale, cesium was the probable cause of the patient's arrhythmia. In animal models, cesium chloride has induced cardiac arrhythmias, including torsade de pointes. It inhibits delayed rectifier potassium channels in the myocardium, causing delayed repolarization and QT‐interval prolongation. Patients with cancer should be aware that alternative remedies may be harmful and ineffective. Because patients may be unlikely to self‐report alternative remedies, health care providers should specifically ask their patients about any alternative treatments they may be taking and should be knowledgeable about their toxicities.
Sunitinib‐Related Fulminant Hepatic Failure: Case Report and Review of the Literature
Authors: Mueller Eric W. , Rockey Michelle L. , Rashkin Mitchell C.
Published: July 2008

Drug‐induced hepatotoxicity is an infrequent but life‐threatening complication. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma and gastrointestinal stromal tumor. However, results from preapproval clinical trials suggest an equivocal hepatic risk profile for sunitinib. We describe a 75‐year‐old woman with renal cell carcinoma who was admitted to the intensive care unit after experiencing fulminant hepatic failure during sunitinib therapy. The patient's hepatic and renal chemistries had been within normal limits throughout four previous cycles of sunitinib therapy spanning 9 months. After the fifth cycle, she complained of a 3‐day history of severe diarrhea and dehydration. Her abnormal laboratory test results included the following: total bilirubin level 5.9 mg/dl, aspartate aminotransferase level 3872 U/L, alanine aminotransferase level 3332 U/L, ammonia level 897 μg/dl, and an international normalized ratio of 4.8. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between sunitinib and hepatotoxicity. Supportive care including aggressive intravenous hydration and reversal of coagulopathy was successful. The patient was discharged home on hospital day 7 without apparent longstanding sequelae. Clinicians should be aware of this possible adverse effect of sunitinib, and continued pharmacovigilance is imperative to accurately quantify the possible risk of sunitinib‐related hepatotoxicity.
Bicalutamide‐Associated Fulminant Hepatotoxicity
Authors: O'Bryant Cindy L. , Flaig Thomas W. , Utz Kenneth J.
Published: July 2008

Bicalutamide is a nonsteroidal antiandrogen used extensively during the start of androgen deprivation therapy with a luteinizing hormone‐releasing hormone agonist to reduce occurrence of the symptoms of tumor flare in patients with metastatic prostate carcinoma. The most common adverse effects of bicalutamide are induced by its pharmacologic property of competitive androgen receptor blockade and include gynecomastia, hot flashes, fatigue, and decreased libido. Although not as common, increases in liver function test results are also seen with bicalutamide therapy. These elevations are typically transient, and patients remain asymptomatic. We describe a 59‐year‐old man with metastatic prostate carcinoma treated with bicalutamide as part of androgen deprivation therapy before starting chemotherapy. At baseline, his liver function test results and serum creatinine concentration were within normal limits, and an abdominal computed tomographic scan did not demonstrate liver metastasis. After 4 days of bicalutamide therapy, the patient came to the emergency department with complaints of abdominal pain, distension, and tenderness. His liver function tests were abnormal, and bicalutamide was discontinued. After 2 days of increasing liver function tests and symptoms of hepatotoxicity, the patient developed tachycardia and hypotension that was resistant to fluid resuscitation. Multiorgan damage was manifested by an alanine aminotransferase level greater than 40 times the upper limit of normal, serum creatinine concentration of 4.2 mg/dl, and troponin I level of 18 ng/ml. The patient died 8 days after bicalutamide therapy was begun secondary to multiorgan failure, most likely as a result of fulminant hepatotoxicity. The Naranjo adverse drug reaction probability scale showed a probable (score of 5) causal relationship between bicalutamide and fulminant hepatotoxicity. Fulminant hepatotoxicity is a rare but potentially fatal adverse effect of bicalutamide. Liver function tests should be monitored before and during bicalutamide therapy, even for patients who have previously completed a course of this therapy with no signs or symptoms of toxicity.
Concomitant Use of Voriconazole and Rifabutin in a Patient with Multiple Infections
Authors: Schwiesow Joshua N. , Iseman Michael D. , Peloquin Charles A.
Published: July 2008

Concomitant administration of azole antifungal agents and rifamycins is contraindicated because an interaction between these drugs results in subtherapeutic azole concentrations. We describe a 30‐year‐old woman with severe pulmonary disease associated with Mycobacterium xenopi and Aspergillus fumigatus, necessitating simultaneous antimycobacterial and antifungal therapy. She was treated with rifabutin—the rifamycin with the least cytochrome P450 (CYP) enzyme induction—and therapeutic drug monitoring was performed so that target serum concentrations of all antimicrobial agents could be achieved. As a result of this monitoring, the frequency of voriconazole 300 mg needed to be increased from twice/day to 3 times/day. The patient's clinical outcome improved dramatically. She was discharged from the hospital and continued treatment for her mycobacterial infection while remaining free of the Aspergillus infection. We believe that careful drug selection combined with therapeutic monitoring of antimicrobial drug serum concentrations is a practical model that clinicians can use to manage coexisting mycobacterial and fungal infections.
Proton Pump Inhibitor Use and Risk of Hip Fractures in Patients without Major Risk Factors
Authors: Kaye James A. , Jick Hershel
Published: July 2008

Study Objective. To estimate the relative risk of hip fracture associated with proton pump inhibitor (PPI) use in a population without major risk factors.

Design. A two‐phase, matched, nested case‐control study.

Data Source. United Kingdom General Practice Research Database (GPRD).

Patients. Phase 1 identified 4414 case patients (aged 50–79 yrs) with an incident hip fracture between 1995 and 2005 who had at least 2 years of recorded history in the GPRD; each case was matched by age, sex, and index date (date of first‐time hip fracture for cases, same date for matched controls) to up to 10 controls who did not have hip fracture. Phase 2 included the 1098 case patients identified as having no major medical risk factors for hip fracture (as assessed in phase 1) and a new set of 10,923 controls without major risk factors for hip fracture matched by sex, age, index date, and duration of history in the GPRD.

Measurements and Main Results. In phase 1, we identified major medical risk factors for hip fracture. In phase 2, we restricted the study to case patients with none of these risk factors and matched them to new controls, who also had none of the risk factors. Data on use of PPIs were collected and compared between the groups. The relative risk (RR) for hip fracture among patients who received any PPI prescription was 0.9 (95% confidence interval 0.7‐1.1) compared with those with no PPI prescription. We found no evidence of an increased risk of hip fracture with increased PPI use. The RR estimates were similar in both sexes and in all age subgroups. No specific PPI was associated with an increased risk of hip fracture.

Conclusion. Use of PPIs does not increase the risk of hip fracture in patients without major risk factors. The difference in results between our study and that of another, which indicated that PPI use increases the risk of hip fracture, may be due to residual confounding or effect modification in the latter study.
Thromboembolic Consequences of Subtherapeutic Anticoagulation in Patients Stabilized on Warfarin Therapy: The Low INR Study
Authors:   Warfarin‐Associated Research Projects and Other Endeavors (WARPED) Consortium, Clark Nathan P. , Witt Daniel M. , Delate Thomas , Trapp Melissa , Garcia David , Ageno Walter , Hylek Elaine M. , Crowther Mark A.
Published: July 2008

Study Objective. To quantify the absolute risk of thromboembolism associated with a significant subtherapeutic international normalized ratio (INR) in patients with previously stable anticoagulation while receiving warfarin.

Design. Retrospective, matched cohort analysis.

Setting. Centralized anticoagulation service in an integrated health care delivery system.

Patients. A total of 2597 adult patients receiving warfarin from January 1998‐December 2005; 1080 patients were in the low INR cohort and were matched to 1517 patients in the therapeutic INR cohort based on index INR date, indication for warfarin, and age.

Measurements and Main Results. Stable, therapeutic anticoagulation was defined as two INR values, measured at least 2 weeks apart, within or above the therapeutic range. The low INR cohort included patients with a third INR value of 0.5 or more units below their therapeutic range. The therapeutic INR cohort included patients with a third therapeutic INR value and no INR value 0.2 or more units below their target INR range in the ensuing 90 days. The primary outcome was anticoagulation‐related thromboembolism during the 90 days after the index INR. Secondary outcomes were times to the first occurrence of anticoagulation‐related complications (bleeding, thromboembolism, or death) in the 90 days after the index INR. Four thromboembolic events (0.4%) occurred in the low INR cohort and one event (0.1%) in the therapeutic INR cohort (p=0.214). The differences in the proportions of thromboembolism, bleeding, or death were not significant between the cohorts (p>0.05). No significant differences were noted in the hazard of thromboembolism, bleeding, or death between the cohorts (p>0.05).

Conclusion. Patients with stable INRs while receiving warfarin who experience a significant subtherapeutic INR value have a low risk of thromboembolism in the ensuing 90 days. The risk was similar to that observed in a matched control population in whom therapeutic anticoagulation was maintained. These findings do not support the practice of anticoagulant bridge therapy for patients stabilized on warfarin therapy to reduce their risk for thromboembolism during isolated periods of subtherapeutic anticoagulation.
An In Vivo‐In Vitro Study of Cefepime and Cefazolin Dialytic Clearance During High‐Flux Hemodialysis
Authors: Maynor Lena M. , Carl Daniel E. , Matzke Gary R. , Gehr Todd W. B. , Farthing Christine , Farthing Don , Brophy Donald F.
Published: July 2008

Study Objectives. To assess the influence of in vitro and in vivo hemodialysis with a new high‐flux dialyzer on the clearance of cefazolin and cefepime; to assess the correlation of in vivo dialytic clearance of these antibiotics with blood flow rate; and to assess the correlation between in vitro and in vivo dialytic clearances of these antibiotics.

Design. Prospective, open‐label, dialysis clearance study.

Setting. A tertiary‐care, university health science center.

Patients. Five adults who received high‐flux hemodialysis 3 times/week.

Intervention. For the in vivo experiment, patients received a single intravenous infusion of cefazolin 1 g and cefepime 1 g before dialysis and then underwent a modified hemodialysis session. For the in vitro experiment, a buffered simulated plasma water (SPW) solution containing cefazolin and cefepime was used. Hemodialysis for both experiments was performed with use of a new high‐flux polysulfone dialyzer.

Measurements and Main Results. Cefazolin and cefepime dialytic clearances were determined at blood and/or SPW flow rates of 100, 200, 300, and 400 ml/minute after a 15‐minute equilibration period. The degree of correlation of in vitro and in vivo clearances with blood flow rate was determined. Cefepime dialytic clearance increased proportionally with blood flow rate (p<0.01), reaching a maximum mean ± SD value of 178.9 ± 24.3 ml/minute at a blood flow rate of 400 ml/minute. Cefazolin dialytic clearance ranged from a mean ± SD of 42.3 ± 7.7 to 52.7 ± 16 ml/minute; no significant correlation was noted between blood flow rate and dialytic clearance. In vitro cefazolin and cefepime dialytic clearances increased proportionally with SPW flow rate (p<0.05). After adjusting the in vitro cefazolin and cefepime dialytic clearances based on their degrees of protein binding, the correlation between the in vitro and in vivo cefepime dialytic clearances was significant (r2=0.91, p=0.04), but no significant correlation was noted between the in vitro and in vivo cefazolin clearances (r2=0.61, p=0.22).

Conclusion. The in vivo hemodialysis clearances of cefepime and cefazolin with the new high‐flux polysulfone dialyzer used in this study are markedly higher than values reported with conventional dialyzers but similar to values observed with other high‐flux hemodialyzers. The in vivo dialytic clearance of cefazolin was significantly lower than the in vitro values, most likely due to cefazolin's high degree of protein binding. These results highlight the limitation of directly applying in vitro data to clinical situations.
Pharmacogenomic Biomarker Information in Drug Labels Approved by the United States Food and Drug Administration: Prevalence of Related Drug Use
Authors: Frueh Felix W. , Amur Shashi , Mummaneni Padmaja , Epstein Robert S. , Aubert Ronald E. , DeLuca Teresa M. , Verbrugge Robert R. , Burckart Gilbert J. , Lesko Lawrence J.
Published: July 2008

Study Objectives. To review the labels of United States Food and Drug Administration (FDA)‐approved drugs to identify those that contain pharmacogenomic biomarker information, and to collect prevalence information on the use of those drugs for which pharmacogenomic information is included in the drug labeling.

Design. Retrospective analysis.

Data Sources. The Physicians' Desk Reference Web site, Drugs@FDA Web site, and manufacturers' Web sites were used to identify drug labels containing pharmacogenomic information, and the prescription claims database of a large pharmacy benefits manager (insuring > 55 million individuals in the United States) was used to obtain drug utilization data.

Measurements and Main Results. Pharmacogenomic biomarkers were defined, FDA‐approved drug labels containing this information were identified, and utilization of these drugs was determined. Of 1200 drug labels reviewed for the years 1945–2005, 121 drug labels contained pharmacogenomic information based on a key word search and follow‐up screening. Of those, 69 labels referred to human genomic biomarkers, and 52 referred to microbial genomic biomarkers. Of the labels referring to human biomarkers, 43 (62%) pertained to polymorphisms in cytochrome P450 (CYP) enzyme metabolism, with CYP2D6 being most common. Of 36.1 million patients whose prescriptions were processed by a large pharmacy benefits manager in 2006, about 8.8 million (24.3%) received one or more drugs with human genomic biomarker information in the drug label.

Conclusion. Nearly one fourth of all outpatients received one or more drugs that have pharmacogenomic information in the label for that drug. The incorporation and appropriate use of pharmacogenomic information in drug labels should be tested for its ability to improve drug use and safety in the United States.
Characterization of Side Population Cells from Human Airway Epithelium
Authors: Hackett Tillie-Louise , Shaheen Furquan , Johnson Andrew , Wadsworth Samuel , Pechkovsky Dmitri V. , Jacoby David B. , Kicic Anthony , Stick Stephen M. , Knight Darryl A.
Published: July 2008

The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45− SP, CD45+ SP, and non-SP cells were isolated and sorted. CD45− SP cells made up 0.12% ± 0.01% of the total epithelial cell population in normal airway but 4.1% ± 0.06% of the epithelium in asthmatic airways. All CD45− SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45− SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45− SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and long-term proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium.

Disclosure of potential conflicts of interest is found at the end of this article.
Regulation of Embryonic Stem Cell Self-Renewal and Pluripotency by Foxd3
Authors: Liu Ying , Labosky Patricia A.
Published: July 2008

The Foxd3 forkhead transcription factor is required for maintaining pluripotent cells in the early mouse embryo and for the establishment of murine embryonic stem cell (ESC) lines. To begin to understand the role of Foxd3 in ESC maintenance, we derived ESC lines from blastocysts that carried two conditional Foxd3 alleles and a tamoxifen-inducible Cre transgene. Tamoxifen treatment produced a rapid and near complete loss of Foxd3 mRNA and protein. Foxd3-deficient ESCs maintained a normal proliferation rate but displayed increased apoptosis, and clonally dispersed ESCs showed a decreased ability to self-renew. Under either self-renewal or differentiation-promoting culture conditions we observed a strong, precocious differentiation of Foxd3 mutant ESCs along multiple lineages, including trophectoderm, endoderm, and mesendoderm. This profound alteration in biological behavior occurred in the face of continued expression of factors known to induce pluripotency, including Oct4, Sox2, and Nanog. We present a model for the role of Foxd3 in repressing differentiation, promoting self-renewal, and maintaining survival of mouse ESCs.

Disclosure of potential conflicts of interest is found at the end of this article.
Insulin-like growth factor-1 delays Fas-mediated apoptosis in human neutrophils through the phosphatidylinositol-3 kinase pathway
Authors: Himpe Eddy , Degaillier Céline , Coppens Astrid , Kooijman Ron
Published: July 2008

Apoptosis of human neutrophils is a crucial mechanism for the resolution of inflammation. We previously showed that insulin-like growth factor-1 (IGF1) delays spontaneous neutrophil apoptosis without influencing the secretion of cytokines by these cells. In the present study, we further addressed the role of IGF1 in regulating neutrophil survival in the presence of other factors present during inflammation, and the mechanism involved in delaying apoptosis. We show that IGF1 delays neutrophil apoptosis triggered by the agonistic anti-Fas antibody CH11 and that the effect of IGF1 is comparable in magnitude to that of the acknowledged anti-apoptotic cytokines interferon-γ (IFNG) and granulocyte–macrophage colony-stimulating factor (GM-CSF; now known as CSF2). Furthermore, IGF1 exerted additional effects on cell survival in the presence of these cytokines. IGF1 did not affect Fas expression or activation by anti-Fas of caspase-8, but inhibited the depolarization of the mitochondrial membrane. Inhibitor studies indicate that the phosphatidylinositol-3 kinase (PI3K) pathway, but not the MEK–ERK pathway, mediates the effects of IGF1. However, in contrast to CSF2, IGF1 did not induce phosphorylation and translocation to the membrane of AKT, the canonical downstream target of PI3K. We therefore speculate that other downstream targets of PI3K are involved in the delay of neutrophil apoptosis by IGF1, possibly through stabilization of the mitochondrial membrane.
Inhibition of GATA2-dependent transactivation of the TSHβ gene by ligand-bound estrogen receptor α
Authors: Nagayama Koji , Sasaki Shigekazu , Matsushita Akio , Ohba Kenji , Iwaki Hiroyuki , Matsunaga Hideyuki , Suzuki Shingo , Misawa Hiroko , Ishizuka Keiko , Oki Yutaka , Noh Jaeduk Yoshimura , Nakamura Hirotoshi
Published: July 2008

Transcriptional repression of the TSH-specific β subunit (TSHβ) gene has been regarded to be specific to thyroid hormone (tri-iodothyronine, T3) and its receptors (TRs) in physiological conditions. However, TSHβ mRNA levels in the pituitary were reported to decrease in the administration of pharmacologic doses of estrogen (17-β-estradiol, E2) and increase in E2 receptor (ER)-α null mice. Here, we investigated the molecular mechanism of inhibition of the TSHβ gene expression by E2-bound E2-estrogen receptor 1 (E2-ERα). In kidney-derived CV1 cells, transcriptional activity of the TSHβ promoter was stimulated by GATA2 and suppressed by THRBs and ERα in a ligand-dependent fashion. Overexpression of PIT1 diminished the E2-ERα-induced inhibition, suggesting that PIT1 may protect GATA2 from E2-ERα targeting by forming a stable complex with GATA2. Interacting surfaces between ERα and GATA2 were mapped to the DNA-binding domain (DBD) of ERα and the Zn finger domain of GATA2. E2-dependent inhibition requires the ERα amino-terminal domain but not the tertiary structure of the second Zn finger motif in E2-ERα-DBD. In the thyrotroph cell line, TαT1, E2 treatment reduced TSHβ mRNA levels measured by the reverse transcription PCR. In the human study, despite similar free thyroxine levels, the serum TSH level was small but significantly higher in post- than premenopausal women who possessed no anti-thyroid antibodies (1.90 μU/ml±0.13 s.e.m. vs 1.47 μU/ml±0.12 s.e.m., P<0.05). Our findings indicate redundancy between T3-TR and E2-ERα signaling exists in negative regulation of the TSHβ gene.
Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats
Authors: Murakami Masahiro , Matsuzaki Toshiya , Iwasa Takeshi , Yasui Toshiyuki , Irahara Minoru , Osugi Tomohiro , Tsutsui Kazuyoshi
Published: July 2008

Gonadotropin-inhibitory hormone (GnIH), a newly discovered hypothalamic RFamide peptide, inhibits reproductive activity by decreasing gonadotropin synthesis and release in birds. The gene of the mammalian RFamide-related peptides (RFRP) is orthologous to the GnIH gene. This Rfrp gene gives rise to the two biologically active peptides RFRP-1 (NPSF) and RFRP-3 (NPVF), and i.c.v. injections of RFRP-3 suppress LH secretion in several mammalian species. In this study, we show whether RFRP-3 affects LH secretion at the pituitary level and/or via the release of GnRH at the hypothalamus in mammals. To investigate the suppressive effects of RFRP-3 on the mean level of LH secretion and the frequency of pulsatile LH secretion in vivo, ovariectomized (OVX) mature rats were administered RFRP-3 using either i.c.v. or i.v. injections. Furthermore, the effect of RFRP-3 on LH secretion was also investigated using cultured female rat pituitary cells. With i.v. administrations, RFRP-3 significantly reduced plasma LH concentrations when compared with the physiological saline group. However, after i.c.v. RFRP-3 injections, neither the mean level of LH concentrations nor the frequency of the pulsatile LH secretion was affected. When using cultured pituitary cells, in the absence of GnRH, the suppressive effect of RFRP-3 on LH secretion was not clear, but when GnRH was present, RFRP-3 significantly suppressed LH secretion. These results suggest that RFRP-3 does not affect LH secretion via the release of GnRH, and that RFRP-3 directly acts upon the pituitary to suppress GnRH-stimulated LH secretion in female rats.
Briefing: Tracking site staff with wireless technology
Authors: Manning James
Published: July 2008

The temporary and constantly changing nature of construction sites creates special challenges that are not found in other industries. The site itself transforms daily, the workers even change from day to day as phases get completed and different subcontractors come and go. Some of the ways in which the latest wireless time and attendance technology can help to monitor staff and maintain site security are described in this article.
UK civil engineering education in the twenty-first century
Authors: Barr B.
Published: July 2008

The paper reviews many of the recent changes in the general and specific education of civil engineering graduates including: grade inflation at GCSE, AS and A level; the pressure on engineering education due to university expansion in non-traditional subject areas; the negative effect of research assessment exercises leading to skewed academic appointments; common teaching for three years for MEng and BEng (Hons) degrees; the proliferation of MSc degrees; the potential threat arising from the Bologna declaration; together with some views from industry. The paper concludes with a proposal to maintain the ‘gold standard’ MEng degree by developing closer relationships between industry and academia via the initial professional development of graduates.
The impact of multiskilling on UK's construction manpower
Authors: Ejohwomu O. A. , Proverbs D. G. , Olomolaiye P.
Published: July 2008

The overall significance of the construction and building services sector internationally cannot be overemphasised. In the UK, the industry currently accounts for 10% gross domestic product (GDP) and employs 2 million people, which is more than 1 in 14 of the total workforce. However, regardless of its output (approximately £65 billion annually) there has been a steady decline in the number of trade entrants into the construction and building services sector. Consequently, the available ‘pool of labour’ is inadequately resourced; productivity is low; the existing labour force is overstressed; there is an increase in site deaths; and a long-term labour shortage is envisaged. Today, the evidence seems to suggest that multiskilling is a tentative redress for ameliorating the skills crisis in the construction and building sectors. A 43-year time-series of data on 23 manpower attributes was evaluated as part of this investigation. The developed linear regression models show that the concept of multiskilling obeys the ‘law of diminishing returns'. That is, a weak relation was found between construction output and a three or more combination of manpower attributes. An optimisation model is prescribed for traditional trades.
Briefing: Culture and mindset—the NEC approach
Authors: Lofty John
Published: July 2008

This is the first of a series of briefings prepared by the NEC Panel to help clients, consultants and contractors in their understanding of the NEC approach when using NEC contracts. This first briefing introduces the positive culture and mindset which are at the heart of the NEC approach.
Briefing: Knowledge and information management for major projects
Authors:   Institution of Civil Engineers ICT Panel
Published: July 2008

This article identifies the issues facing the adoption of best practice on information management for major projects and the practical steps needed to address the knowledge gap. A number of projects were consulted by the authors in preparing the article.
An Innovative Bitumen Extraction Process for Oil Sands: Sand Reduction Technology (SRT) and Bitumen Concentration
Authors: Yildirim Erdal , Gregoli A.A. , Jamshar J.A. , Rimmer D.P.
Published: July 2008

In 1991, Canadian Occidental undertook the development of a new process designed for efficient extraction of bitumen from oil sands which would be suitable for employment at remote sites. The new process, Sand Reduction Technology (SRT), is based on the separation of solids from an oil sand slurryin a system of hydrocyclones. The sand and clay in the slurry exit as a concentrated tails stream containing 70 to 75 percent solids. The remaining bitumen, water, and fine solids form an overhead stream containing 5 to 15percent bitumen. The objective of this new program was to test process concepts for efficient removal of water from this stream to produce a concentratedbitumen product stream containing 40 to 75 percent bitumen.

Following a series of laboratory investigations, a small scale processdevelopment unit (PDU) was constructed in Canadian Occidental's laboratory in Tulsa to test the bitumen concentration process. The PDU was sized to feed 10Ibs/min of oil sands to a slurry preparation unit which consisted of a heatedtumbler. The slurry was screened to remove oversize solids and unconditioned oil sands and was then pumped to a one-inch hydrocyclone for separation of most of the slurry solids. The overhead stream from the hydrocyclone was tested in several process options to concentrate the contained bitumen, which averaged about 8 percent in this stream. Oil sands feed for this project was obtained from Syncrude Canada Ltd. and consisted of two grades described as "typicalgrade" and "low grade".

Twenty-two PDU runs were made from November 1993 through June 1994. The operating plan for each run included a start-up period in which process conditions were established, followed by a one-hour material balance period. Two basic bitumen concentration concepts were evaluated, with several variations of each. The first process concept was based on the flotation of bitumen from the cyclone overhead stream. A four-cell Denver flotation unit was employed for this phase of the project, which included eight PDU runs. Good bitumen recovery was achieved in the flotation tests with up to 99 percent retention of bitumen in this part of the process. The bitumen was also concentrated, with bitumen concentration in the flotation froth averaging greater than 40 percent during optimal run periods.
Gauge Accreditation Facility -- History and Future Recommendations
Authors: Vik S. A. , Botto G. , Kviljo K. , Roffey M.
Published: July 2008

This paper presents the history of the ‘Gauge Accreditation Facility’ project. Twelve large oil companies sponsored a joint industry project to test and compare a large number of memory and permanent pressure gauges. The project experienced a significant improvement in gauge quality and services during and after the project. This paper will present information about the project focusing on memory gauges as these were the bulk of the gauges tested.
Petroleum Engineering Education: Innovation to Meet the Needs of Industry
Authors: Schenewerk Philip , Alman Rex
Published: July 2008

In the grand scheme of engineering disciplines, petroleum engineering is a relative newcomer. Early curricula focused on the entire field of endeavor from exploration to refining depending on the expertise of the faculty. The modem curriculum, however, has been fairly standardized through the process of accreditation. Throughout its relatively short history there have been numerous arguments about what elements of the curriculum were more important, strong fundamentals, and applied sciences vs. specialization in petroleum engineering; business skills vs. humanities and social sciences.

Today, as we are all aware, our industry is in a continual state of change. Since 1988 extraction has lost 53% of its workforce. Industry has become more efficient, doing more with better technology and fewer people. The industry, which has always had an international side, has moved overseas as companies seek exploration opportunities outside the US. As the perceived need for petroleum engineers in the US has declined, so has the number of petroleum engineering departments. These trends have been a cause of concern to petroleum engineering educators because of the historically strong ties between industry and university petroleum engineering departments.

Over the last five years, a series of three colloquia has been held to discuss issues related to petroleum engineering education. The first colloquium, held during the summer of 1991, focused on supply and demand issues along with a variety of issues related to perspectives on the educational needs of future petroleum engineering students (Wilhite, 1991). During this first colloquium, schools were asked to indicate their desired enrollment levels. Evaluating these desired enrollments showed that enrollments would be in excess of the projected needs of industry. It was clear that if enrollments were to rise, other employment outlets for petroleum engineers would need to be found.
A New Cost Effective Philosophy for Upgrading Passive Fire Protection
Authors: Aune Stig , Skotnes Ole , Rasmussen Olav , Schumacher Robert R.
Published: July 2008

A platform complex in the Norwegian Sector of the North Sea has been in operation since 1983. As the installation is exposed to a rather hostile environment, the original spray-on passive fire protection has experienced extensive degradation and a replacement or upgrade was required in order to maintain the fire resistance rating originally planned for when the coating was applied.

As part of the replacement and upgrade project, a new philosophy for passive fire protection was developed. The new philosophy focused on demonstrating the actual need of replacement, something that was determined through a thorough evaluation of the different functions the passive fire protection would have for the different fire compartments. The functions evaluated took into account the protection of personnel, environment and assets. Dimensioning fire loads were defined considering fire types, heat loads and fire duration.

Every type of structure; wall, floor or ceiling (with associated load-bearing members) was analysed, and functional requirements to the structures and areas were established for a range of fire scenarios. Based on this, the need for passive fire protection was determined and summarised in tables in order to ease any future replacements or upgrades. A plot-plan indicating the required fire protection was then developed for all areas of each platform.

Applying this new methodology on the first platform (of four) resulted in significant savings in the time spent offshore replacing the degraded passive fire protection. This again resulted in a cost reduction of more than 1 million dollars for this platform alone.

Based on the success of the new passive fire protection philosophy with regards to time and cost savings, it has been decided that this also will be applied in the design phase of any new platforms that the company will build in the future.
Impact of Composition Variation with Depth on Volatile Oil
Authors: Syahrial E.
Published: July 2008

It has been known that the distribution of hydrocarbon components in a fluid column is affected of gravity. Many authors have shown the effect of composition variation within a hydrocarbon column due to gravity. In thick reservoirs as the depth increases, the mole fraction of the lighter hydrocarbon decreases, whereas the heavy fraction fraction increases. These variations may affect reservoir fluid properties considerably. In studying reservoir processes, especially with miscible displacements, it is essential to have of underlying mechanisms.

In this paper, we investigate the effect of composition variation with depth on volatile oil under depletion and miscible gas processes. A ternary diagram was used to identify the process displacement mechanisms at different locations. A new efficient compositional simulation approach was used to model the volatile oil reservoir bahaviour.

It was shown that the decreasing light component with depth caused different miscible displacement processes as the oil composition move toward limiting tie line in the ternary diagram. Saturation and reservoir pressures variation with depth were not linear in a thick reservoir. This non linearity increased with the increased in volatility of the oil. In the case of depletion, the concentration of light component decreased below its original composition in the produced layers. In vaporising-gas drive the light component gradually vaporized from the bottom to the top of reservoir, whereas the intermediate component decreased below its original composition from the bottom to the top of the reservoir.
Views on Exercise Maintenance: Variations Among Patients With Rheumatoid Arthritis
Authors: Swärdh Emma , Biguet Gabriele , Opava Christina H
Published: July 2008

Background and Purpose

Individuals with rheumatoid arthritis (RA) often have to make changes in exercise behavior in order to gain and sustain health benefits. The purpose of this study was to explore and describe ways of understanding exercise maintenance among individuals with RA who had already started to exercise.

Participants

Fourteen women and 4 men with RA of at least 2 years’ duration, selected from 4 hospitals or primary health care physical therapy clinics, participated. They had exercised regularly at least twice weekly during the previous 2 months with various levels of support from a physical therapist, and they had attempted to exercise without support outside of the health care environment during the previous year.

Method

A phenomenographic approach was used to analyze semistructured interviews. A pattern of categories of descriptions was constructed based on the participants’ conceptions and ways of understanding the phenomenon of exercise maintenance.

Results

Five categories were identified: “external control,” “sticks and carrots,” “a joint venture,” “the easy way,” and “on one's own terms.” The categories became clear by elucidating 2 aspects related to exercise maintenance: (1) the way the participants talked about and experienced the type of support needed and (2) personal factors.

Discussion and Conclusion

The results highlight the importance of finding the proper context and support for each patient's needs. Furthermore, preparing for exercise maintenance by strengthening the patient's beliefs in his or her ability to exercise in different settings, by discussing pros and cons of exercise, and by exploiting the patient's ability to adapt and continue exercise outside of the health care environment might be valuable.
Habitual Physical Activity Behavior of Patients After Primary Total Hip Arthroplasty
Authors: Wagenmakers Robert , Stevens Martin , Zijlstra Wiebren , Jacobs Monique L , van den Akker-Scheek Inge , Groothoff Johan W , Bulstra Sjoerd K
Published: July 2008

Background and Purpose

Despite recognized health benefits of physical activity, little is known about the habitual physical activity behavior of patients after total hip arthroplasty (THA). The purpose of this study was to analyze this behavior and the fulfillment of guidelines for health-enhancing physical activity of these patients compared with a normative population.

Subjects and Methods

The participants were 273 patients who had undergone a primary THA (minimum of 1 year postoperatively). Comparisons were made between this group and 273 age- and sex-matched individuals from a normative population. Comparisons also were made between participants with THA under 65 years of age and those 65 years of age and older and among participants with THA in different Charnley classes. Level of physical activity was assessed with the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH).

Results

No significant differences in total amount of physical activity or time spent in different categories of physical activity were found between the THA group and the normative group. Participants with THA spent significantly more minutes in activities of moderate intensity compared with the normative group. Participants with THA who were under 65 years of age were significantly more active than older participants with THA. Charnley class had significant effects on time spent at work, time spent in moderate-intensity activities, and total amount of activity, with the least activity performed by participants in Charnley class C. The guidelines were met by 51.2% of the participants with THA and 48.8% of the normative population. Female participants met the guidelines less frequently than male participants in both the combined groups (odds ratio=0.50, 95% confidence interval=0.35–0.72, P<.001) and the THA group (odds ratio=0.48, 95% confidence interval=0.28–0.80, P=.001).

Discussion and Conclusion

The results suggest that patients after THA are at least as physically active as a normative population. Nevertheless, a large percentage of these patients do not meet the guidelines; therefore, they need to be stimulated to become more physically active.
Possible New Reaction Mechanisms of Dideoxynucleosides as Anti-Aids Drugs
Authors: Mamantov Andrew
Published: July 2008

Evidence is presented that a major class of drugs, the dideoxynucleosides (ddNs) and nucleoside/nucleotide analogues, may inhibit the symptoms of acquired immunodeficiency syndrome (AIDS) by initiation of inactivation at the ribonucleotide reductase (RNR) enzyme stage and/or inactivation of reverse transcriptase enzyme or at a stage more initial than that of the currently accepted DNA chain termination hypothesis. For example, it has been previously shown that ribonucleotide diphosphate reductase (RDPR) and ribonucleotide triphosphate reductase (RTPR) are inactivated with 2′-chloro-2 ‘-deoxyuridine 5′-diphosphate-([3′-3H]ClUDP) and triphosphate ([3′-3H]ClUTP) by reaction with an intermediate furanone, Scheme 2. RDPR has also been inactivated by 2‘-azido-2‘-deoxyuridine 5‘-diphosphate (N3UDP). Furthermore, addition of hydroxyurea to RNR can inhibit DNA synthesis which results in a rapid depletion of limiting deoxynucleotide triphosphate (dNTP) pools. There are similar perturbations of dNTP pools upon interaction of human RNR with 3‘-azido-2‘,3 ‘-dideoxythymidine (AZT), in human cell studies involving AZT/HIV and in adenosine/coformycin experiments in relation to inherited immunodeficiency, Table 1. Also, the herein proposed reduction mechanisms of nucleotides by RNR ( e.g., a single electron transfer from the nucleotide base to the phenol moiety of the tyrosyl radical of RNR via a pathway involving the thiyl radical of a cysteine residue) can also account for the chemistry of some antiretroviral drugs, the ddNs. Analyses are presented that the RNR reductions of regular unsubstituted nucleotides may occur predominantly via initial 2’ C-H abstraction instead of the originally proposed 3’ C-H abstraction mechanism. Also, it is noted that the fate of the phenol moiety of the tyrosyl unit in some RNR reactions with 2‘-halo-2‘-deoxynucleotides is not clear. The proposed reaction mechanisms may provide guidance for the development of potentially effective anti-AIDS drugs.