bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of the efficacy and side-effect profile of lower doses of intrathecal morphine in patients undergoing total knee arthroplasty
Authors: Hassett Patrick , Ansari Bilal , Gnanamoorthy Pachaimuthu , Kinirons Brian , Laffey John G 
Published: September 2008

Abstract

Background
Intrathecal (IT) morphine provides excellent post-operative analgesia, but causes multiple side effects including nausea and vomiting (PONV), pruritus and respiratory depression, particularly at higher doses. The lowest effective dose of spinal morphine in patients undergoing total knee arthroplasty is not known.

Methods
We evaluated the analgesic efficacy and side effect profile of 100 – 300 μg IT morphine in patients undergoing elective total knee replacement in this prospective, randomized, controlled, double-blind study. Sixty patients over the age of 60 undergoing elective knee arthroplasty were enrolled. Patients were randomized to receive spinal anaesthesia with 15 mg Bupivacaine and IT morphine in three groups: (i) 100 μg; (ii) 200 μg; and (iii) 300 μg.

Results
Both 200 μg and 300 μg IT morphine provided comparable levels of postoperative analgesia. However, patients that received 100 μg had greater pain postoperatively, with higher pain scores and a greater requirement for supplemental morphine. There were no differences between groups with regard to PONV, pruritus, sedation, respiratory depression or urinary retention.

Conclusion
Both 200 μg and 300 μg provided comparable postoperative analgesia, which was superior to that provided by 100 μg IT morphine in patients undergoing total knee arthroplasty. Based on these findings, we recommend that 200 μg IT morphine be used in these patients.

Trial registration
ClinicalTrials.gov Identifier NCT00695045
The role of polyclonal intravenous immunoglobulin in treating HIV-infected children with severe bacterial infections: A retrospective cohort study
Authors: Huang Lyen C , Myer Landon , Jaspan Heather B 
Published: September 2008

Abstract

Background
Mortality among HIV-infected children in developing countries remains high after serious bacterial infections despite the use of antibiotics. Intravenous immunoglobulin (IVIG) has been used as an adjuvant therapy to treat these infections, but little data exists regarding its efficacy, and previous studies have focused on IVIG as a prophylactic agent. We examined the impact of IVIG as an adjuvant therapy in reducing mortality and length of hospital stay in HIV-infected children with serious bacterial infections.

Methods
This retrospective study focused on pediatric admissions at a large urban hospital between 2002 and 2006. Children between the ages of one month and nine years of age with laboratory confirmed HIV-status, serious bacterial infection, no prior exposure to IVIG, and a hospital length of stay of 5 days or more, were eligible for inclusion.

Results
A total of 140 children (median age 1.2 years) met inclusion criteria; lower respiratory tract infection was diagnosed in 94 (67%) of the children, while 74 (53%) had bacterial sepsis. Fifty-four (39%) children were receiving antiretroviral therapy and 39 (28%) were receiving tuberculosis treatment. Overall 73 (52%) were treated with IVIG, with the majority (74%) of children receiving a single dose. Thirteen (9%) died during their hospital admission. In crude analysis IVIG was significantly associated with increased mortality was (Odds Ratio (OR): 5.8; 95% Confidence Interval (CI): 1.2–27.1) and this association was weakened by adjustment for other predictors of mortality (OR 4.3, 95% CI 0.7–27.9, p = 0.123). IVIG use was also associated with longer hospital stays.

Conclusion
Administration of one to three doses of IVIG during the acute phase of illness does not appear to reduce mortality or the length of hospital stays in HIV-infected children with serious bacterial infections. However, the retrospective nature of this study makes confounding by indication difficult to control and further studies regarding the timing, dosing, and method of administration are required. Nonetheless the routine use of IVIG in resource-limited settings should be carefully considered given its high cost.
Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria
Authors: Leoratti Fabiana MS , Durlacher Rui R , Lacerda Marcus VG , Alecrim Maria G , Ferreira Antonio W , Sanchez Maria CA , Moraes Sandra L 
Published: September 2008

AbstractBackgroundThe development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response againstPlasmodium falciparumblood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions.MethodsDifferent isotypes againstP. falciparumblood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population.ResultsThe highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic individuals with this allele, suggesting the protective role of IgG2 in this population.ConclusionTogether, the results suggest a differential regulation in the anti-P. falciparumantibody pattern in different clinical expressions of malaria and showed that even in unstable transmission areas, protective immunity against malaria can be observed, when the appropriated antibodies are produced.
Comprehensive study of proteasome inhibitors against Plasmodium falciparum laboratory strains and field isolates from Gabon
Authors: Kreidenweiss Andrea , Kremsner Peter G , Mordmüller Benjamin 
Published: September 2008

Abstract

Background
The emergence and spread of Plasmodium falciparum resistance to almost all available antimalarial drugs necessitates the search for new chemotherapeutic compounds. The ubiquitin/proteasome system plays a major role in overall protein turnover, especially in fast dividing eukaryotic cells including plasmodia. Previous studies show that the 20S proteasome is expressed and catalytically active in plasmodia and treatment with proteasome inhibitors arrests parasite growth. This is the first comprehensive screening of proteasome inhibitors with different chemical modes of action against laboratory strains of P. falciparum. Subsequently, a selection of inhibitors was tested in field isolates from Lambaréné, Gabon.

Methods
Epoxomicin, YU101, YU102, MG132, MG115, Z-L3-VS, Ada-Ahx3-L3-VS, lactacystin, bortezomib (Velcade®), gliotoxin, PR11 and PR39 were tested and compared to chloroquine- and artesunate-activities in a standardized in vitro drug susceptibility assay against P. falciparum laboratory strains 3D7, D10 and Dd2. Freshly obtained field isolates from Lambaréné, Gabon, were used to measure the activity of chloroquine, artesunate, epoxomicin, MG132, lactacystin and bortezomib. Parasite growth was detected through histidine-rich protein 2 (HRP2) production. Raw data were fitted by a four-parameter logistic model and individual inhibitory concentrations (50%, 90%, and 99%) were calculated.

Results
Amongst all proteasome inhibitors tested, epoxomicin showed the highest activity in chloroquine-susceptible (IC50: 6.8 nM [3D7], 1.7 nM [D10]) and in chloroquine-resistant laboratory strains (IC50: 10.4 nM [Dd2]) as well as in field isolates (IC50: 8.5 nM). The comparator drug artesunate was even more active (IC50: 1.0 nM), whereas all strains were chloroquine-resistant (IC50: 113 nM).

Conclusion
The peptide α',β'-epoxyketone epoxomicin is highly active against P. falciparum regardless the grade of the parasite's chloroquine susceptibility. Therefore, inhibition of the proteasome is a highly promising strategy to develop new antimalarials. Epoxomicin can serve as a standard to compare new inhibitors with species-specific activity.
Child-OIDP index in Brazil: Cross-cultural adaptation and validation
Authors: Castro Rodolfo AL , Cortes Maria IS , Leão Anna T , Portela Margareth C , Souza Ivete PR , Tsakos Georgios , Marcenes Wagner , Sheiham Aubrey 
Published: September 2008

Abstract

Background
Oral health-related quality of life (OHRQoL) measures are being increasingly used to introduce dimensions excluded by normative measures. Consequently, there is a need for an index which evaluates children's OHRQoL validated for Brazilian population, useful for oral health needs assessments and for the evaluation of oral health programs, services and technologies. The aim of this study was to do a cross-cultural adaptation of the Child Oral Impacts on Daily Performances (Child-OIDP) index, and assess its reliability and validity for application among Brazilian children between the ages of eleven and fourteen.

Methods
For cross-cultural adaptation, a translation/back-translation method integrated with expert panel reviews was applied. A total of 342 students from four public schools took part of the study.

Results
Overall, 80.7% of the sample reported at least one oral impact in the last three months. Cronbach's alpha was 0.63, the weighted kappa 0.76, and the intraclass correlation coefficient (ICC) 0.79. The index had a significant association with self-reported health measurements (self-rated oral health, satisfaction with oral health, perceived dental treatment needs, self-rated general health; all p < 0.01).

Conclusion
It was concluded that the Child-OIDP index is a measure of oral health-related quality of life that can be applied to Brazilian children.
Fatigue testing of three peristernal median sternotomy closure techniques
Authors: Wangsgard Cameron , Cohen David J , Griffin Lanny V 
Published: September 2008

Abstract

Background
Failure of a sternotomy closure because of closure system fatigue is a complication that may result in dehiscence and put the individual at risk for serious complications. The purpose of this study was to assess the fatigue performance of three peristernal median sternotomy closure techniques (figure-of-eight stainless-steel wires, figure-of-eight stainless-steel cables, or Pectofix Dynamic Sternal Fixation [DSF] stainless-steel plates) in order to quantify the potential risk of fatigue failure of these devices when subject to cyclic loads in physiologically relevant loading directions.

Study Design
All tests were conducted on polyurethane foam sternal models. A cardiothoracic surgeon divided each sternal model longitudinally and repaired it with a closure device. Tests were performed using a materials testing system that applied cyclic loading in a uniaxial direction until the test model catastrophically broke or data run-out occurred. For each loading direction (lateral distraction and longitudinal shear), five trials of each closure technique were tested. Life data and location of device failure (if present) were evaluated. Statistical analysis was performed using regression with life data allowed for correlation between life data and the various closure techniques to develop risk assessment curves for each device.

Results
The data show that the figure-of-eight stainless-steel cable and the DSF plate systems are considerably less likely to fail under both lateral distraction and longitudinal shear cyclic loading conditions as compared to the figure-of-eight stainless-steel wire system. Moreover, the figure-of-eight stainless-steel cable system is the most resistant to failure, particularly for high cycle counts.

Conclusion
This study in addition to Cohen and Griffin's earlier published biomechanical comparison of the ultimate strength of these same three closure techniques provide extensive experimental evidence regarding the mechanical differences among these three peristernal median sternotomy closure techniques. All data support the hypothesis that both the DSF plate system and the stainless-steel cable system offer important advantages over figure-of-eight wire closure techniques; although twisted wires are the weak-link in the systems we tested.
Tv-RIO1 – an atypical protein kinase from the parasitic nematode Trichostrongylus vitrinus
Authors: Hu Min , LaRonde-LeBlanc Nicole , Sternberg Paul W , Gasser Robin B 
Published: September 2008

Abstract

Background
Protein kinases are key enzymes that regulate a wide range of cellular processes, including cell-cycle progression, transcription, DNA replication and metabolic functions. These enzymes catalyse the transfer of phosphates to serine, threonine and tyrosine residues, thus playing functional roles in reversible protein phosphorylation. There are two main groups, namely eukaryotic protein kinases (ePKs) and atypical protein kinases (aPKs); RIO kinases belong to the latter group. While there is some information about RIO kinases and their roles in animals, nothing is known about them in parasites. This is the first study to characterise a RIO1 kinase from any parasite.

Results
A full-length cDNA (Tv-rio-1) encoding a RIO1 protein kinase (Tv-RIO1) was isolated from the economically important parasitic nematode Trichostrongylus vitrinus (Order Strongylida). The uninterrupted open reading frame (ORF) of 1476 nucleotides encoded a protein of 491 amino acids, containing the characteristic RIO1 motif LVHADLSEYNTL. Tv-rio-1 was transcribed at the highest level in the third-stage larva (L3), and a higher level in adult females than in males. Comparison with homologues from other organisms showed that protein Tv-RIO1 had significant homology to related proteins from a range of metazoans and plants. Amino acid sequence identity was most pronounced in the ATP-binding motif, active site and metal binding loop. Phylogenetic analyses of selected amino acid sequence data revealed Tv-RIO1 to be most closely related to the proteins in the species of Caenorhabditis. A structural model of Tv-RIO1 was constructed and compared with the published crystal structure of RIO1 of Archaeoglobus fulgidus (Af-Rio1).

Conclusion
This study provides the first insights into the RIO1 protein kinases of nematodes, and a foundation for further investigations into the biochemical and functional roles of this molecule in biological processes in parasitic nematodes.
Trial femoral head loss in to the soft tissues of pelvis during primary total hip replacement: a case report
Authors: Vertelis Arunas , Vertelis Linas , Tarasevicius Sarunas 
Published: September 2008

Abstract
The loss of trial femoral head in the soft tissues is a rare per operative complication in total hips replacement. We report the loss of the femoral head in surrounding hip joint soft tissues and unsuccessful attempts to locate and remove it. Surgeons should be aware of such complication as trial femoral heads usually are made from non radiolucent material and cannot be detected by regular x-ray examination during surgery. The industry should consider manufacturing trial femoral heads from x-ray visible material.
Dynamic activation of bone morphogenetic protein signaling in collagen-induced arthritis supports their role in joint homeostasis and disease
Authors: Daans Melina , Lories Rik JU , Luyten Frank P 
Published: September 2008

Abstract
Introduction
Rheumatoid arthritis is a chronic systemic autoimmune disease affecting peripheral joints and leading to loss of joint function. The severity and outcome of disease are dependent on the balance between inflammatory/destructive and homeostatic or repair pathways. Increasing evidence suggests a role for bone morphogenetic protein (BMP) signaling in joint homeostasis and disease.

Methods
Activation of BMP signaling in collagen-induced arthritis as a model of rheumatoid arthritis was studied by immunohistochemistry and Western blot for phosphorylated SMAD1/5 at different time points. Expression of different BMP ligands and noggin, a BMP antagonist, was determined on synovium and cartilage extracts of arthritic knees, at different time points, with quantitative polymerase chain reaction. At the protein level, BMP2 and BMP7 were studied with immunohistochemistry. Finally, the effect of anti-tumor necrosis factor-alpha (TNFα) treatment on the expression of BMP2, BMP7, and growth and differentiation factor-5 (GDF5) in synovium and cartilage of arthritic knees was investigated.

Results
A time-dependent activation of the BMP signaling pathway in collagen-induced arthritis was demonstrated with a dynamic and characteristic expression pattern of different BMP subfamily members in synovium and cartilage of arthritic knees. As severity increases, the activation of BMP signaling becomes more prominent in the invasive pannus tissue. BMP2 is present in cartilage and the hyperplastic lining layer. BMP7 is found in the sublining zone and inflammatory infiltrate. Treatment with etanercept slowed down progression of disease, but no change in expression of GDF5, BMP2, and BMP7 in synovium was found; in the cartilage, however, blocking of TNFα increased the expression of BMP7.

Conclusions
BMP signaling is dynamically activated in collagen-induced arthritis and is partly TNFα-independent. TNFα blocking increased the expression of BMP7 in the articular cartilage, possibly enhancing anabolic mechanisms. Different types of source and target cells are recognized. These data further support a role for BMP signaling in arthritis.
Menopause, postmenopausal hormone use and serum uric acid levels in US women – The Third National Health and Nutrition Examination Survey
Authors: Hak A Elisabeth , Choi Hyon K 
Published: September 2008

Abstract
Introduction
Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representative sample of women.

Methods
Using data from 7662 women aged 20 years and older in the Third National Health and Nutrition Examination Survey (1988 to 1994), we examined the relation between menopause, postmenopausal hormone use and serum uric acid levels. We used multivariate linear regression to adjust for other risk factors for hyperuricaemia such as dietary factors, age, adiposity, alcohol use, renal function, hypertension and diuretic use.

Results
Menopause was associated with higher serum uric acid levels. After adjusting for covariates, serum uric acid levels among women with natural menopause and surgical menopause were greater than premenopausal women by 0.34 mg/dl (95% confidence interval [CI], 0.19 to 0.49) and 0.36 mg/dl (95% CI, 0.14 to 0.57), respectively. Current postmenopausal hormone use was associated with a lower serum uric acid level among postmenopausal women (multivariate difference, 0.24 mg/dl [95% CI, 0.11 to 0.36]). The serum uric acid levels increased with increasing age categories (crude difference between 20 to 29 years and 70 years and over = 1.03 mg/dl, p for trend < 0.001), but this increase was not present after adjusting for other covariates (p for trend = 0.66).

Conclusions
These findings from a nationally representative sample of US women indicate that menopause is independently associated with higher serum uric acid levels, whereas postmenopausal hormone use is associated with lower uric acid levels among postmenopausal women. The age-associated increase in serum uric acid levels in women may be explained by menopause and other age-related factors.
Dickkopf-Like1 Regulates Postpubertal Spermatocyte Apoptosis and Testosterone Production
Authors: Dakhova Olga , O'Day Diana , Kinet Noe , Yucer Nur , Wiese Mary , Shetty Gunapala , Ducy Patricia 
Published: September 2008

Dickkopf-like1 (Dkkl1) encodes a glycoprotein secreted by postmeiotic male germ cells. We report here that adult Dkkl1-deficient males have elevated sperm counts caused by a decrease in postpubertal spermatocyte apoptosis and display, upon aging, increased local production of testosterone. Molecular analyses identified the Fas death ligand (FasL) as a target for Dkkl1 pro-apoptotic activity in adult mice. Accordingly, adult FasL-deficient gld mice display an increased sperm count and decreased spermatocyte apoptosis phenotype similar to the one observed in Dkkl1-deficient mice. We also show that the elevated testosterone level observed in aging Dkkl1-deficient males is secondary to increased expression in Leydig cells of CYP11A and CYP17, two genes implicated in steroidogenesis. Furthermore, treatment of Leydig cells with Dkkl1 decreases DNA binding and transcriptional activity of steroidogenic factor 1, a pivotal regulator of gene expression in testis. Thus, this study establishes Dkkl1 as a negative regulator of adult testis homeostasis and identifies a novel, Dkkl1/FasL-dependent, regulation that specifically controls the number of postpubertal spermatocytes.Dickkopf-like 1 negatively regulates adult testis biology by promoting spermatocyte apoptosis via Fas ligand activation and by limiting testosterone synthesis in Leydig cells.
Prospective Study of High-Dose Cabergoline Treatment of Prolactinomas in 150 Patients
Authors: Ono Masami , Miki Nobuhiro , Kawamata Takakazu , Makino Rena , Amano Kosaku , Seki Toshiro , Kubo Osami , Hori Tomokatsu , Takano Kazue 
Published: September 2008

Context: Cabergoline fails to normalize hyperprolactinemia in a considerable proportion of prolactinomas, especially macroadenomas.
Objective: We examined the effect of individualized high-dose cabergoline treatment on hyperprolactinemia in prolactinomas.
Patients: The study included 122 women and 28 men (93 microadenomas and 57 macroadenomas). Forty-seven had undergone transsphenoidal surgery. According to the preceding medical treatment, the participants were separated into untreated (group U; n = 60), intolerant (group I; n = 64), and resistant (group R; n = 26) groups.
Interventions: We promptly increased cabergoline dose on the basis of individual prolactin levels. Length of treatment was 1 yr.
Results: Cabergoline normalized hyperprolactinemia in all patients except one. The proportion of prolactin normalization in both groups U and I was 83% at 3 months and 95% at 6 months. By contrast, that in group R was 35% at 3 months and 58% at 6 months. Mean cabergoline dose in milligrams per week at the time of prolactin normalization was 2.0 ± 0.3 in group U, 0.9 ± 0.1 in group I, and 5.2 ± 0.6 in group R. Prolactin normalization rate at the 3 mg/wk dose was 84% overall but only 35% in group R. Serum progesterone or testosterone levels, diminished in 122 women or 16 men, respectively, were recovered in all except one resistant and four postmenopausal or panhypopituitary patients.
Conclusion: Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.