bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Follicle-Stimulating-Hormone-Stimulated Dimeric Inhibin and Estradiol Responses as Indicators of Granulosa Cell Function in Polycystic Ovary Syndrome and Normal Women
Authors: Wachs Deborah S. , Coffler Mickey S. , Malcom Pamela J. , Chang R. Jeffrey
Published: May 2006

Context: Follicular phase secretion of inhibin B, like that of estradiol (E2), correlates with the quantity and quality of developing follicles. However, it has not been established whether inhibin B responses to gonadotropin stimulation parallel those of E2 as a reflection of granulosa cell functional capacity.

Objective: Our objective was to determine whether inhibin B responses to FSH stimulation are similar to those of E2 in women with polycystic ovary syndrome (PCOS) and normal women.

Design and Setting: We conducted a prospective study to compare ovarian responses in two groups of women at a general clinical research center in a tertiary academic medical center.

Patients: Women with PCOS, 18–35 yr (n = 19), and normal ovulatory controls, 18–35 yr (n = 7), were recruited for study.

Interventions: Serum samples were measured over a 24-h period after an iv injection of recombinant human FSH, 150 IU.

Main Outcome Measures: Serum E2, inhibin A, and inhibin B responses after FSH administration were assessed.

Results: In PCOS women, the 24-h production of inhibin B and E2 after FSH was significantly greater than that of normal controls. Within the PCOS group, the fold change in inhibin B was significantly greater than that of E2. Inhibin A responses between groups were similar and of markedly lower magnitude.

Conclusions: FSH-stimulated inhibin B responses may be employed to assess the functional capacity of granulosa cells in PCOS and normal women.
C-3 Epimers Can Account for a Significant Proportion of Total Circulating 25-Hydroxyvitamin D in Infants, Complicating Accurate Measurement and Interpretation of Vitamin D Status
Authors: Singh Ravinder J. , Taylor Robert L. , Reddy G. Satyanarayana , Grebe Stefan K. G.
Published: May 2006

Context: We have recently introduced liquid chromatography-tandem mass spectrometry (LC-MS/MS) for 25-hydroxyvitamin D2 (25OHD2) and 25OHD3 testing. During subsequent clinical use, we identified significantly elevated results in some infants. We hypothesized this might represent assay interference caused by C-3 epimers of 25OHD2 or 25OHD3.

Objective: Our aims were to 1) determine the prevalence of C-3 epimers of 25OHD2 or 25OHD3 in human serum, and 2) identify the patient populations that might be affected.

Study Design: We modified our LC-MS/MS method to allow detection of C-3 epimers. We retested specimens from four patient groups with the new method and an extracted RIA: 1) children less than 1 yr old, 2) children 1–18 yr old, 3) adults aged 20–87 yr with liver disease, and 4) adults aged 19–91 yr without liver disease.

Results: In 172 children from group 1 with detectable 25OHD2 or 25OHD3, we identified C-3 epimers in 39 (22.7%). The epimers contributed 8.7–61.1% of the total 25-OHD. There was an inverse relationship between patient age and epimer percentage (r = 0.48; P < 0.002). The RIA gave accurate 25-OHD results that correlated with the modified LC-MS/MS method. No C-3 epimers were detected in any of the other groups.

Conclusions: Significant concentrations of C-3 epimers of 25OHD2 or 25OHD3 are commonly found in infants. This can lead to overestimation of 25-OHD levels. Measurements in children less than 1 yr should therefore be performed with an assay that allows accurate detection of 25-OHD in the presence of its C-3 epimers.
Gli3-mediated somiticFgf10expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes
Authors: Veltmaat Jacqueline M. , Relaix Frédéric , Le Lendy T. , Kratochwil Klaus , Sala Frédéric G. , van Veelen Wendy , Rice Ritva , Spencer-Dene Bradley , Mailleux Arnaud A. , Rice David P. , Thiery Jean Paul , Bellusci Saverio
Published: May 2006

Little is known about the regulation of cell fate decisions that lead to the formation of five pairs of mammary placodes in the surface ectoderm of the mouse embryo. We have previously shown that fibroblast growth factor 10(FGF10) is required for the formation of mammary placodes 1, 2, 3 and 5. Here,we have found that Fgf10 is expressed only in the somites underlying placodes 2 and 3, in gradients across and within these somites. To test whether somitic FGF10 is required for the formation of these two placodes, we analyzed a number of mutants with different perturbations of somitic Fgf10 gradients for the presence of WNT signals and ectodermal multilayering, markers for mammary line and placode formation. The mammary line is displaced dorsally, and formation of placode 3 is impaired in Pax3ILZ/ILZ mutants, which do not form ventral somitic buds. Mammary line formation is impaired and placode 3 is absent in Gli3Xt-J/Xt-J and hypomorphic Fgf10 mutants, in which the somitic Fgf10 gradient is shortened dorsally and less overall Fgf10 is expressed, respectively. Recombinant FGF10 rescued mammogenesis in Fgf10-/- and Gli3Xt-J/Xt-J flanks. We correlate increasing levels of somitic FGF10 with progressive maturation of the surface ectoderm, and show that full expression of somitic Fgf10, co-regulated by GLI3, is required for the anteroposterior pattern in which the flank ectoderm acquires a mammary epithelial identity. We propose that the intra-somitic Fgf10 gradient, together with ventral elongation of the somites,determines the correct dorsoventral position of mammary epithelium along the flank.
Palmitoylation determines the function of Vac8 at the yeast vacuole
Authors: Subramanian K. , Dietrich L. E. P. , Hou H. , LaGrassa T. J. , Meiringer C. T. A. , Ungermann C.
Published: May 2006

Palmitoylation stably anchors specific proteins to membranes, but may also have a direct effect on the function of a protein. The yeast protein Vac8 is required for efficient vacuole fusion, inheritance and cytosol-to-vacuole trafficking. It is anchored to vacuoles by an N-terminal myristoylation site and three palmitoylation sites, also known as the SH4 domain. Here, we address the role of Vac8 palmitoylation and show that the position and number of substrate cysteines within the SH4 domain determine the vacuole localization of Vac8: stable vacuole binding of Vac8 requires two cysteines within the N-terminus, regardless of the combination. Importantly, our data suggest that palmitoylation adds functionality to Vac8 beyond simple localization. A mutant Vac8 protein, in which the palmitoylation sites were replaced by a stretch of basic residues, still localizes to vacuole membranes and functions in cytosol-to-vacuole transport, but can only complement the function of Vac8 in morphology and inheritance if it also contains a single cysteine within the SH4 domain. Our data suggest that palmitoylation is not a mere hydrophobic anchor required solely for localization, but influences the protein function(s).
Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells
Authors: Utama B. , Shen Y. H. , Mitchell B. M. , Makagiansar I. T. , Gan Y. , Muthuswamy R. , Duraisamy S. , Martin D. , Wang X. , Zhang M.-X. , Wang J. , Wang J. , Vercellotti G. M. , Gu W. , Li Wang X.
Published: May 2006

Human cytomegalovirus (HCMV) infection results in endothelial dysfunction, typically known as dysregulated apoptosis, and aberrant expression and sub-cellular localization of p53, a tumor suppressor that accumulates at the late stage of infection. In this study, we examined three hypotheses that could be responsible for HCMV-induced cytoplasmic p53 accumulation at the later stage of infection: hyperactive nuclear export, cytoplasmic p53 tethering and delayed p53 degradation. Leptomycin B treatment, a nuclear export inhibitor, was unable to reduce cytoplasmic p53, thereby eliminating the hyperactive nuclear export mechanism. The findings that nascent p53 still entered nuclei after the nuclear export inhibition indicated that cytoplasmic tethering may play a minor role. Cytoplasmic p53 was still observed after the translation activities were blocked by cycloheximide. There was more than an eight-fold increase in the cytoplasmic p53 half-life with abnormal p53 ubiquitination. Taken together, these results suggest that delayed degradation could be responsible for the cytoplasmic p53 accumulation. The general slow-down of the proteasomal activity and the dysregulated p53 ubiquitination process at the later stage of infection could contribute to the reduced cytoplasmic p53 degradation and might be relevant to dysregulated endothelial apoptosis. The HCMV-induced changes in p53 dynamics could contribute to endothelial dysfunction.
Upregulation of chicken p15INK4b at senescence and in the developing brain
Authors: Kim S.-H. , Rowe J. , Fujii H. , Jones R. , Schmierer B. , Kong B.-W. , Kuchler K. , Foster D. , Ish-Horowicz D. , Peters G.
Published: May 2006

In mammalian cells, products of the INK4a-ARF locus play major roles in senescence and tumour suppression in different contexts, whereas the adjacent INK4b gene is more generally associated with transforming growth factor β (TGF-β)-mediated growth arrest. As the chicken genome does not encode an equivalent of INK4a, we asked whether INK4b and/or ARF contribute to replicative senescence in chicken cells. In chicken embryo fibroblasts (CEFs), INK4b levels increase substantially at senescence and the gene is transcriptionally silenced in two spontaneously immortalised chicken cell lines. By contrast, ARF levels are unaffected by prolonged culture or immortalisation. These expression patterns resemble the behaviour of INK4a and ARF in human fibroblasts. However, short-hairpin RNA (shRNA)-mediated knockdown of chicken INK4b or ARF provides only modest lifespan extension, suggesting that other factors contribute to senescence in CEFs. As well as underscoring the importance of the INK4b-ARF-INK4a locus in senescence, these findings imply that the encoded products have assumed different roles in different evolutionary niches. Although ARF RNA is not detectable in early chicken embryos, the INK4b transcript is expressed in the roof-plate of the developing hind-brain, consistent with a role in limiting cell proliferation.
Maximum Equivalent Stress in a Pin-Loaded Lug Subject to Inclined Loading
Authors: Strozzi A , Baldini A , Nascimbeni M
Published: May 2006

The elastic maximum equivalent stress in a pin-loaded, straight- or taper-shanked, round-ended lug subject to inclined loading is investigated using the finite element and the boundary element methods, and, partly, photoelasticity. The influence of the load direction, of the ratio between the bore diameter and lug width, and of the shank taper angle are particularly addressed. In addition, the effects of the axial length of the lug trunk and, partially, of the initial clearance between the lug bore and pin are numerically examined in the presence of a loading variously inclined to the lug axis. An interpolating expression for the maximum equivalent stress as a function of the ratio between the bore diameter and lug width, taper angle, and load inclination angle is proposed.
An Effective Route for Porous Ferrihydrite Preparation from Layered Double Hydroxide Precursors
Authors: Xia Wei , Meng Weiqing , Yu Ranbo , Xing Xianran , Wang Dan , Chen Yunfa , Takano Mikio
Published: May 2006

A porous ferrihydrite has been synthesized from layered double hydroxide precursors via selective extraction. The characterization results show that the porous ferrihydrite possesses not only large total pore volume but also uniform micropore size distribution, which make it exhibit a good charge/discharge capacity and cycling performance as the lithium battery cathode.
Multiplex Gene Mutation Analysis Using Affinity Capillary Electrophoresis in a Single Microfluidic Channel
Authors: Inoue Akira , Ito Toshiyuki , Sato Kae , Hosokawa Kazuo , Makino Kimiko , Maeda Mizuo
Published: May 2006

This communication describes a novel strategy for multiplex gene mutation analysis in a single microfluidic channel. The method is based on affinity capillary electrophoresis with multiple probes immobilized to the sieving polymer matrix. Single-step detection of two point mutations is demonstrated with a simple setup and procedure.
Enhancement of Singlet Oxygen Sensitization of Tetraphenylporphyrin by Silylation
Authors: Horiuchi Hiroaki , Tanaka Toru , Yoshimura Kimio , Sato Kenta , Kyushin Soichiro , Matsumoto Hideyuki , Hiratsuka Hiroshi
Published: May 2006

Photophysical and singlet oxygen sensitization processes of 5,10,15,20-tetrakis(4-trimethylsilylphenyl)porphyrin have been studied. It was found out that the quantum yield (ΦΔ) of singlet oxygen production increased by the silylation of 5,10,15,20-tetraphenylporphyrin (TPP). The silylation does not affect the photophysical processes of TPP but enhances the sensitization efficiency of singlet oxygen by the triplet sensitizer (fΔT). This enhancement can be explained by the suppression of the process from the triplet encounter complex composed of the triplet sensitizer and ground-state oxygen to the ground-state sensitizer and oxygen.
Synthesis and Photovoltaic Properties of Tetrathiafulvalene–Oligothiophene–Fullerene Triads
Authors: Kanato Hiroki , Narutaki Masashi , Takimiya Kazuo , Otsubo Tetsuo , Harima Yutaka
Published: May 2006

Novel tetrathiafulvalene–oligothiophene–fullerene triads have been synthesized as single-component materials for photovoltaic cells. They showed somewhat improved photovoltaic performances, when compared to the corresponding oligothiophene–fullerene dyads.
A Facile Route to Prepare Mesoporous Anatase TiO2 Nanotubes Assembly
Authors: Fan Wugang , Gao Lian
Published: May 2006

Anatase TiO2 nanotube assembly was prepared by vapor-phase method using carbon nanotubes as template. Large surface area and mesoporous structure of the product favor the applications in gas sensing and photocatalysis.
In-cement technique for revision hip arthroplasty
Authors: Quinlan J. F. , O’Shea K. , Doyle F. , Brady O. H.
Published: May 2006

The in-cement technique for revision hip arthroplasty involves retaining the original cement-bone interface. This has been proven to be a biomechanically stronger method than recementing after complete removal of the original cement mantle.

This study reviewed a series of 54 consecutive revision hip arthroplasty procedures, using the in-cement technique, between November 1999 and November 2003. Clinical and radiological follow-up included functional assessment.

There were 54 procedures performed in 51 patients, whose mean age at surgery was 70.3 years (45 to 85). A total of 42 were available at a mean follow-up of 29.2 months (6 to 51). There was no radiological evidence of loosening. Functional assessments were available for 40 patients who had a mean Harris hip score of 85.2 (51.9 to 98.5), a mean Oxford hip score of 19.6 (12 to 41), a mean UCLA activity profile score of 5.9 (3 to 8) and a mean SF-36 score of 78.0 (31.6 to 100).

The in-cement technique provides consistent, high functional outcomes and should be considered in appropriately selected cases.
The effect of a neck-retaining femoral implant on leg-length inequality following total hip arthroplasty
Authors: Khanduja V. , Tek V. , Scott G.
Published: May 2006

The aim of this study was to assess whether a femoral component which retained the neck reduced the incidence of leg-length inequality following total hip arthroplasty. A retrospective review was undertaken of 130 consecutive primary total hip arthroplasties performed between April 1996 and April 2004 using such an implant. There were 102 suitable patients for the study. Standardised pre- and post-operative pelvic radiographs were measured by an independent investigator to the nearest millimetre.

The leg-length inequality was reduced from a mean pre-operative value of −0.71 cm to a mean of 0.11 cm post-operatively. Of the 102 patients 24 (23.5%) had an equal leg-length post-operatively, and 95 (93.1%) had a leg-length inequality between −1 cm and 1 cm.
Posterior lumbar interbody fusion with an autogenous iliac crest bone graft in the treatment of pyogenic spondylodiscitis
Authors: Lee J. S. , Suh K. T.
Published: May 2006

There are few reports on the treatment of pyogenic lumbar spondylodiscitis through the posterior approach using a single incision. Between October 1999 and March 2003 we operated on 18 patients with pyogenic lumbar spondylodiscitis. All underwent posterior lumbar interbody fusion using an autogenous bone graft from the iliac crest and pedicle screws via a posterior approach. The clinical outcome was assessed using the Frankel neurological classification and the criteria of Kirkaldy-Willis. Under the Frankel classification, two patients improved by two grades (C to E), 11 by one grade, and five showed no change. The Kirkaldy-Willis functional outcome was excellent in five patients, good in ten and fair in three. Bony union was confirmed six months after surgery in 17 patients, but in one patient this was not achieved until two years after operation. The mean lordotic angle before operation was 20° (−2° to 42°) and the mean lordotic angle at the final follow-up was 32.5° (17° to 44°). Two patients had a superficial wound infection and two a transient root injury. Posterior lumbar interbody fusion with an autogenous iliac crest bone graft and pedicle screw fixation via a posterior approach can provide satisfactory results in pyogenic spondylodiscitis.
Results of arthrodesis in neuropathic feet
Authors: Schwarz R. J. , Macdonald M. R. C. , van der Pas M.
Published: May 2006

We describe the results of arthrodesis for the treatment of recurrent acute neuropathic bone disease in 24 feet and of chronic disease with deformity in 91 feet, undertaken between January 1984 and December 2003. All were due to leprosy.

Correction of the deformity was achieved in 80 of 106 feet (76%) and fusion in 97 of 110 feet (88%). In the 24 feet in which recurrent neuropathic bone disease was the reason for surgery, 17 (71%) obtained stability while in seven (29%) symptoms recurred postoperatively. Complications were experienced following 58 of the 110 operations (53%). In patients presenting primarily with deformity with a minimum follow-up of two years (79 feet), there was a reduced frequency of ulceration in 40 (51%). Normal footwear could be worn by 32 patients (40%) after surgery, while 40 (51%) required a moulded insole. Arthrodesis of the ankle in the neuropathic foot due to leprosy has a good overall rate of success although the rate of complications is high.
Continuous monitoring of the performance of hip prostheses
Authors: Hardoon S. L. , Lewsey J. D. , Gregg P. J. , Reeves B. C. , van der Meulen J. H. P.
Published: May 2006

New brands of joint prosthesis are released for general implantation with limited evidence of their long-term performance in patients. The CUSUM continuous monitoring method is a statistical testing procedure which could be used to provide prospective evaluation of brands as soon as implantation in patients begins and give early warning of poor performance. We describe the CUSUM and illustrate the potential value of this monitoring tool by applying it retrospectively to the 3M Capital Hip experience.

The results show that if the clinical data and methodology had been available, the CUSUM would have given an alert to the underperformance of this prosthesis almost four years before the issue of a Hazard Notice by the Medical Devices Agency. This indicates that the CUSUM can be a valuable tool in monitoring joint prostheses, subject to timely and complete collection of data. Regional or national joint registries provide an opportunity for future centralised, continuous monitoring of all hip and knee prostheses using these techniques.
The relationship between acetabular retroversion and osteoarthritis of the hip
Authors: Kim W. Y. , Hutchinson C. E. , Andrew J. G. , Allen P. D.
Published: May 2006

Excessive acetabular cover secondary to a retroverted acetabulum causes pincer impingement, which may cause early osteoarthritis of the hip. Our aim was to determine if there was a relationship between acetabular version and osteoarthritis of the hip. Using image processing and analysis software we studied 117 CT images of the hip in patients aged less than 65 years who had undergone a CT virtual colonoscopy. The mean CT joint space of the 18 hips with acetabular retroversion was narrower compared with the 99 hips with normal acetabular alignment (p < 0.0001). A correlation of r = 0.46 (p < 0.01) was found between right hip acetabular version and the mean right hip joint space and of r = 0.31 (p = 0.02) between left hip acetabular version and the mean left hip joint space. Acetabular retroversion is associated with radiological evidence of osteoarthritis of the hip. An understanding of the mechanical basis of osteoarthritis of the hip allows early treatment of the underlying structural abnormality and prevents progression of the degenerative condition.
Percutaneous drilling for the treatment of secondary osteonecrosis of the knee
Authors: Marulanda G. , Seyler T. M. , Sheikh N. H. , Mont M. A.
Published: May 2006

Osteonecrosis of the knee comprises two separate disorders, primary spontaneous osteonecrosis which is often a self-limiting condition and secondary osteonecrosis which is associated with risk factors and a poor prognosis. In a series of 61 knees (38 patients) we analysed secondary osteonecrosis of the knee treated by a new technique using multiple small percutaneous 3 mm drillings.

Total knee replacement was avoided in 59 knees (97%) at a mean follow-up of 3 years (2 to 4). Of the 61 knees, 56 (92%) had a successful clinical outcome, defined as a Knee Society score greater than 80 points. The procedure was successful in all 24 knees with small lesions compared with 32 of 37 knees (86%) with large lesions. All the procedures were performed as day cases and there were no complications. This technique appears to have a low morbidity, relieves symptoms and delays more invasive surgery.
An alternative method for the treatment of nonunion of the tibia with bone loss
Authors: Sen C. , Eralp L. , Gunes T. , Erdem M. , Ozden V. E. , Kocaoglu M.
Published: May 2006

In this retrospective study we evaluated the method of acute shortening and distraction osteogenesis for the treatment of tibial nonunion with bone loss in 17 patients with a mean age of 36 years (10 to 58). The mean bone loss was 5.6 cm (3 to 10). In infected cases, we performed the treatment in two stages. The mean follow-up time was 43.5 months (24 to 96). The mean time in external fixation was 8.0 months (4 to 13) and the mean external fixator index was 1.4 months/cm (1.1 to 1.8). There was no recurrence of infection. The bone evaluation results were excellent in 16 patients and good in one, while functional results were excellent in 15 and good in two. The complication rate was 1.2 per patient.

We conclude that acute shortening and distraction osteogenesis is a safe, reliable and successful method for the treatment of tibial nonunion with bone loss, with a shorter period of treatment and lower rate of complication.
Boost your surgical training: visit South Africa
Authors: Millar Tim
Published: May 2006

Bottlenecks to the progression of surgical careers have been around since the year dot. Not so long ago, the bottleneck was in progressing from senior registrar to consultant surgeon. Then it was shifted to getting onto an SpR rotation. Soon the problem may be securing a foundation post or an 'ST1' post. Looking further into the future, the bottleneck may once again return to obtaining a consultant post, as Certificate of Completion of Training holders are forced to accept non-consultant 'specialist' posts or to take up short-term jobs in the independent sector. Another possibility is that the post of 'senior consultant' or 'head of department' will be created and hence there will be one final bottleneck before retirement.

Surgery has always been a desirable and competitive field of medicine. Bottlenecks are here to stay. All we can do as individuals is to strive to be the best we can be, for ourselves and for our patients.

In this month's Trainees' Forum we hear how one trainee has managed the gap between basic and higher surgical training and at the same time given his training a lift, by going abroad. It seems his surgical experience and skills were hugely boosted while his horizons were broadened. It is possible that as our training hours reduce, this may be something that more and more trainees consider…
What's in a name?
Authors: Morrison MCT
Published: May 2006

'A rose by any other name may smell as sweet' but words are important as they confer clarity of communication and understanding. It may be fashionable for politicians, managers and accountants to abuse words but in surgery words should be used precisely if any sort of misunderstanding is to be avoided between ourselves – and, more importantly, between ourselves and our patients.
Basic surgical training outcomes in the era of the EWTD
Authors: Frost BM , Beaton C , Hopper AN , Stephens MR , Lewis WG
Published: May 2006

The European Working Time Directive (EWTD) represents the latest challenge to surgical training in the UK, following Calmanisation and the implementation of the New Deal on junior doctors' hours. Compliance with the EWTD in the UK demands shift working patterns and as such it has received a mixed response from the UK medical profession. While physicians in training are relatively content with the regulations of the EWTD, surgical trainees have voiced concerns regarding the potential impact of an altered working week on their clinical experience and training as well as quality of life.
Thinking globally, acting locally: the College's international activities
Authors: Thomas Bill , Kelly Andrea
Published: May 2006

The College has a long tradition of pioneering the highest standards of care and professional ethics. At this time of globalising health agendas it is uniquely positioned to offer itself as an international resource, particularly regarding education and training, and also to access the experience of other surgical communities worldwide. The development of institutional links in both the developed and developing world has the potential to offer major benefits all round, especially in terms of developing professional solidarity and a unified voice for surgery.
Presidential visit to Ghana
Authors: Armitage James , Cathcart Paul , Gooneratne Mayoni
Published: May 2006

The College president Mr Bernard Ribeiro was invited by the West African College of Surgeons (WACS) to participate in its annual conference in Ghana in February 2006. Along with the Association of Surgeons of Great Britain and Ireland (ASGBI), our College had also been asked by the conference committee to run an intercollegiate Basic Surgical Skills (BSS) course together with a Research Methods course. Mr Martyn Coomer, head of research at the College, assembled a team that included Professor Jerry Kirk (former Council member), Dr Jan van der Meulen (director of the College's clinical effectiveness unit) and three of the College's research fellows.
Human factors – what's that about?
Authors: Mitchell David
Published: May 2006

On 22 June 2006 the Faculty of Dental Surgery will be running a one-day conference entitled Implementing Human Factors in Clinical Practice. The subject of the course sounds strange and perhaps a little important but what exactly are human factors?
Teamworking in dentistry
Authors: Pocock Ian
Published: May 2006

July 2006 will see a major change for dentistry. This is when the General Dental Council (GDC) will begin the task of registering four new groups of dental care professionals (DCPs): dental nurses, orthodontic therapists, clinical dental technicians and dental technicians. These are added to those groups already regulated by the GDC: dentists, dental therapists and dental hygienists.
Steroid Therapy for a Case of Severe Drug-Induced Cholestasis
Authors: Giannattasio Antonietta , D'ambrosi Mariangela , Volpicelli Monica , Iorio Raffaele
Published: May 2006

Objective:

To report a Severe case of cholestatic liver disease successfully treated with corticosteroids following combined therapy with clarithromycin and nimesulide.

Case Summary:

A 15-year-old girl was admitted with cholestasis probably related to treatment with clarithromycin and nimesulide for an upper respiratory tract infection. Other causes of liver disease (infections, metabolic liver disorders, genetic cholestatic syndromes, autoimmune diseases, primary biliary tract disorders) were excluded. Liver biopsy showed a severe canalicular cholestasis with bile plugs in dilated bile canaliculi, giant cell transformation, and portal and lobular infiltrate. An objective causality assessment suggested that cholestasis was probably related to clarithromycin and/or nimesulide use. No benefit was derived from a course of ursodeoxycholic acid therapy. Since the patient experienced a progressive worsening in cholestasis, prednisone was started after 20 days. This therapy was promptly followed by improvement in clinical and laboratory test results. After 2 months of prednisone treatment, the patient became symptom-free with normal liver function tests.

Discussion:

The manifestations of drug-induced hepatotoxicity are highly variable, ranging from asymptomatic hypertransaminemia to fulminant hepatic failure. No specific treatment for drug-induced hepatotoxicity exists. Early recognition and drug withdrawal are the keys to management of hepatotoxicity, but in some cases, liver disease may persist despite discontinuation of the drug. Possible advantages of corticosteroid therapy have not been well demonstrated.

Conclusions:

Application of the Naranjo probability scale indicates a probable relationship between cholestasis and nimesulide plus clarithromycin use. This case draws attention to a possible therapeutic option for some cases of drug-induced hepatotoxicity that show a severe course without any sign of improvement.
Coxibs Versus Combination NSAID and PPI Therapy for Chronic Pain: An Exploration of the Risks, Benefits, and Costs
Authors: Hur Chin , Chan Andrew T , Tramontano Angela C , Gazelle G Scott
Published: May 2006

Objective:

To systematically review studies qualitatively to compare the risks (gastrointestinal [Gl] and cardiovascular) and benefits (pain control) of cyclooxygenase-2 inhibitors (coxibs) relative to an alternative therapy of a nonselective nonsteroidal antiinflammatory drug (NSAID) combined with a proton-pump inhibitor (PPI) and explore circumstances when coxibs may be appropriate.

Methods:

Relevant studies were identified through a search of MEDLINE (Ovid Technologies, 1985–November 2005; English language, clinical trial), PubMed (1985–November 2005; English language, clinical trial, humans), and the Cochrane Collaboration using the terms selective COX-2 inhibitors and coxibs, as well as the various chemical names for specific coxib agents. Studies that compared a coxib with a nonselective NSAID and provided data concerning our outcomes of interest were included and categorized by the outcome variable, as well as by the specific coxib studied.

Results:

The majority of the numerous studies that evaluated pain as an endpoint showed no difference between coxib and nonselective NSAID therapy. However, while limited, preliminary safety data regarding the effects of both classes on the upper and lower Gl tract suggest coxib superiority. Although coxibs are associated with an increased risk of cardiovascular adverse events (CVEs) compared with placebo, this effect has not been conclusively shown compared with nonselective NSAIDs. Currently, coxib therapy is more expensive than combination therapy using a nonselective NSAID plus a PPI.

Conclusions:

Compared with combination therapy including a nonselective NSAID and PPI, coxibs provide equivalent pain control and may have a lower Gl tract complication profile, but at an unknown increased risk of CVEs and a greater financial cost. Coxib therapy may be an appropriate treatment for chronic pain in select patients with higher risks of Gl complications, lower risk of CVEs, and in whom greater cost is not a restraint.
Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir
Authors: Bates Duane E , Herman Robert J
Published: May 2006

Objective:

To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.

Case Summary:

A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms.

Discussion:

Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966–May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage.

Conclusions:

An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine–protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25–50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3–5 days after the protease inhibitors are started.
Vancomycin-Induced Elevation of Liver Enzyme Levels
Authors: Cadle Richard M , Mansouri Mohammad D , Darouiche Rabih O
Published: May 2006

Objective:

To report a case of oral vancomycin-induced elevation of liver enzyme levels.

Case Summary:

A 57-year-old man with multiple medical conditions requiring systemic antibiotic therapy developed numerous Clostridium difficile–associated enterocolitis episodes. The patient did not respond adequately to oral metronidazole, as evidenced by his continuing diarrhea. He was treated with oral vancomycin on 5 separate occasions (with doses from 125 to 500 mg/day), each of which resulted in significant elevations in alanine aminotransferase (to 371 U/L) and aspartate aminotransferase (to 203 U/L) levels. The elevations resolved on each occasion with discontinuation of vancomycin.

Discussion:

Vancomycin, a glycopeptide antibiotic, has primary activity against gram-positive bacteria. Oral vancomycin can be used for the treatment of C. difficile–associated enterocolitis in patients who fail to respond to or are intolerant to metronidazole therapy. Oral vancomycin has very poor bioavailability and, as of May 4, 2006, has not been associated with hepatic toxicity. Inflammatory bowel disease processes can result in increased absorption of oral vancomycin.

Conclusions:

This is the first reported case of oral vancomycin–induced elevation of hepatic enzyme levels. Use of the Naranjo probability scale indicated that this was a probable adverse drug-associated event.
Withdrawal from Lorazepam in Critically III Children
Authors: Dominguez Karen D , Crowley Mark R , Coleman Denise M , Katz Robert W , Wilkins Diana G , Kelly H William
Published: May 2006

Background:

Sedatives are used in critically ill children to facilitate mechanical ventilation. Although tolerance and withdrawal are associated with use of sedatives, information about withdrawal from benzodiazepines in children is limited.

Objective:

To document the occurrence of lorazepam withdrawal in critically ill children and identify predictors for the development of withdrawal.

Methods:

This prospective, investigational, open-label study enrolled pediatric patients receiving a continuous infusion of lorazepam for at least 72 hours. The lorazepam dosage was tapered in a uniform fashion over 6 days by decreasing the total daily dose by 50% every other day on 3 occasions; it was then discontinued. The occurrence of withdrawal from lorazepam was determined by pediatric intensive care unit attending physicians based on clinical judgment. Patients were assessed for withdrawal twice daily beginning 48 hours after the initiation of the lorazepam taper. Assessments were continued for 72 hours after lorazepam discontinuation or until the patient experienced withdrawal, whichever came first. Patient demographic, sedative dosing, and lorazepam serum concentration data were collected to identify risk factors for withdrawal.

Results:

Twenty-nine patients completed the study. They received lorazepam for a median duration of about 21 days, and withdrawal occurred in 7 patients. There were no significant differences in demographic variables, lorazepam dosage or other sedative therapy, or lorazepam serum concentrations between patients with withdrawal and those without withdrawal. No predictors of withdrawal were identified.

Conclusions:

Withdrawal occurred in 24% of critically ill children receiving long-term sedation from lorazepam. Risk factors for withdrawal are unknown.
Physical and Chemical Stability of Pemetrexed in Infusion Solutions
Authors: Zhang Yanping , Trissel Lawrence A
Published: May 2006

Background:

Pemetrexed is a multitargeted, antifolate, antineoplastic agent that is indicated for single-agent use in locally advanced or metastatic non-small-cell lung cancer after prior chemotherapy and in combination with cisplatin for the treatment of malignant pleural mesothelioma not treatable by surgery. Currently, there is no information on the long-term stability of pemetrexed beyond 24 hours.

Objective:

To evaluate the longer-term physical and chemical stability of pemetrexed 2, 10, and 20 mg/mL in polyvinyl chloride (PVC) bags of dextrose 5% injection and NaCI 0.9% injection.

Methods:

Triplicate samples of pemetrexed were prepared in the concentrations and infusion solutions required. Evaluations for physical and chemical stability were performed initially and over 2 days at 23 °C protected from light and exposed to fluorescent light, and over 31 days of storage at 4 °C protected from light. Physical stability was assessed using turbidimetric and particulate measurement as well as visual observation. Chemical stability was evaluated by HPLC.

Results:

All pemetrexed solutions remained chemically stable, with little or no loss of pemetrexed over 2 days at 23 °C, protected from light and exposed to fluorescent light, and over 31 days of storage at 4°C, protected from light. The room temperature samples were physically stable throughout the 48 hour test period. However, pemetrexed admixtures developed large numbers of microparticulates during refrigerated storage exceeding 24 hours.

Conclusions:

Pemetrexed is chemically stable for 2 days at room temperature and 31 days refrigerated in dextrose 5% injection and NaCI 0.9% injection. However, substantial numbers of microparticulates may form in pemetrexed diluted in the infusion solutions in PVC bags, especially during longer periods of refrigerated storage. Limiting the refrigerated storage period to the manufacturer-recommended 24 hours will limit particulate formation.
Pharmacoeconomics Impact of Linezolid on Economic Outcomes and Determinants of Cost in a Clinical Trial Evaluating Patients with MRSA Complicated Skin and Soft-Tissue Infections
Authors: McKinnon Peggy S , Sorensen Sonja V , Liu Larry Z , Itani Kamal MF
Published: May 2006

Background:

In clinical trials, linezolid has demonstrated higher clinical cure rates and shorter hospital duration for patients than has vancomycin for the treatment of complicated skin and soft-tissue infections (cSSTIs).

Objective:

To assess economic outcomes of linezolid versus vancomycin and evaluate determinants of treatment costs for cSSTIs.

Methods:

Economic data were obtained from US subjects enrolled in a multinational, open-label, clinical trial of cSSTIs caused by suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects were randomized to receive intravenous or oral linezolid or intravenous vancomycin for 7–21 days. Costs for each patient were evaluated by applying nationally representative per diem hospital costs by hospital ward. Intravenous administration costs were applied to the duration of intravenous treatment. Factors contributing to the cost of therapy were evaluated using multivariate regression analysis.

Results:

Seven hundred seventeen US patients were included in the study. Demographics were similar between treatment groups. Length of stay and duration of intravenous therapy were shorter for linezolid-treated patients. Mean ± SD cost for intent-to-treat population patients treated with linezolid versus vancomycin was $4865 ± 4367 versus $5738 ± 5190, respectively (p = 0.017), and in the MRSA population was $4881 ± 3987 versus $6006 ± 5039, respectively (p = 0.041). Factors significantly associated with increased cost included vancomycin therapy, age, and comorbidities, including diabetes. After adjusting for all other factors, treatment with linezolid was associated with significantly lower treatment costs compared with vancomycin.

Conclusions:

Linezolid therapy was associated with improved clinical outcomes and significantly lower treatment costs than was vancomycin. The largest cost advantage was demonstrated in patients with documented MRSA cSSTIs.
Improving Police Performance with Human Performance Technology (HPT): Watch One, Do One, Teach One
Authors: Pullen William , De Champlain Yvon , Muir Graham
Published: May 2006

Effective policing is an expectation of citizens and communities, a priority concern for the funding jurisdiction, and a matter of accountability and professional pride for police forces. Starting in 2003, the Royal Canadian Mounted Police (RCMP) began a force-wide effort to improve performance in criminal investigations and more broadly to enhance operational readiness. The Bridging the Gap (BTG) initiative used Human Performance Technology (HPT) to find, assess, and remove performance barriers. This is one of the first large-scale applications of HPT in policing. To date, more than 70 detachments and units across Canada have used this process. There are encouraging results. Accelerated and expanded implementation is being planned. The process will be integrated with RCMP performance management systems and business planning.
Film spectatorship between queer theory and feminism: transcultural readings
Authors: Dias Belidson , Sinkinson Susan
Published: May 2006

This article presents an emergent stance in critical literature on visual culture education. A study focused on queer and feminist spectatorship, it considers intersections among critical pedagogy, art education, film, feminist studies, queer studies and transculturalism. Through the
lenses of postcolonialism, feminism and queer theory, it pursues an understanding of how a shift from traditional models of spectatorship to feminist and queer spectatorship might affect teaching and learning in visual culture education. It constitutes a dialogue between two scholars concerned
with spectatorship as a pedagogical device and includes a critical discussion of Pedro Almodúvar and Trinh T. Minh-ha's films because they expose the subject as a crucial element for understanding spectatorship and subjectivity in visual culture education.
Reviews
Authors: Trafí Laura , Batezat Maria-Lucia Batezat
Published: May 2006

Understanding Art: A Guide for Teachers, Martin Wenham, (2003) London: Paul Chapman Publishing. 164 pp., ISBN 0-7619-7477-6 (hbk), £50; ISBN 0-7619-7478-4 (pbk), £17.99

Drawing and Painting: Children and Visual Representation, John Matthews (2003),
2nd edn. London: Paul Chapman Publishing, 225 pp., ISBN 0-7619-4785-X (hbk), £60.00; ISBN 0-7619-4786-8 (pbk), £18.99
Integrating dance and drawing in the kindergarten curriculum in Taiwan
Authors: Shu-Ying Liu
Published: May 2006

This paper and the images therein report on an action research that investigated and developed strategies for teacher training in Taiwan. The aim was to help generalist teachers to develop young children's abilities to make, perform and appreciate dance. The research used Mollie Davies'
Movement Framework (DMF) as a basis for exploring ways in which drawing and painting can be used to motivate kindergarten children to dance and help them to reflect upon it. DMF prioritizes body, space, dynamics and relationships (i.e. what the body does, where it moves, how it moves and with
whom). The research was also informed by John Matthews' theory of figurative representation and action representation (2003) and his explanation of how young children's drawings and paintings are action based and influenced by their previous experiences of movement.
Book Reviews
Authors: Mary L Blatherwick
Published: May 2006

Social and Critical Practices in Art Education, Dennis Atkinson and Paul Dash (eds.), (2005) Stoke-on-Trent: Trentham Books, 164 pp., ISBN 1-85856-311-9 (pbk), £18.99
Pinhead politics? Fox News versus the Canadian regulators
Authors: Regan Shade Leslie
Published: May 2006

Typically, the New York Times isn’t strong on presenting Canadian news to its readers - unlike the Canadian counterpart, The Globe and Mail, which features a daily diet of American news - politics and entertainment. In the last year the New York Times’s
Canadian-focused articles included topics such as antismoking legislation in Nunavut, potential terrorist ties to Canada, acrimonious debates over border safety, the travails of ageing boomers and seniors crossing the border to avail themselves of cheaper Canadian pharmaceuticals, legalized
gay marriages, hockey, sordid politics (a patronage scandal in the Liberal party), softwood lumber disputes under NAFTA, the decriminalization of marijuana, and the synergy between Prime Minister Martin and rock star Bono.
A modest proposal: the class-action case against television
Authors: Rowland Wade
Published: May 2006

First it was big tobacco. Now, some of the victors in those multibillion-dollar David-and-Goliath class-action suits have turned their guns on the fast food industry, charging that junk food is responsible for a public health disaster no less appalling than tobacco’s. They have
snack food giants like Kraft and Frito Lay running scared, stoking up their PR machines. The basic defence being offered is very similar to the one put up by the tobacco industry, and it’s based on freedom of choice. It amounts to arguing that nobody holds a gun to your head to make
you eat deep-fried onion rings or Big Macs - we all have the power to choose what we consume.
Understanding the emergence of digital media
Authors: Domingo David
Published: May 2006

With this volume, Pablo J. Boczkowski plants the roots to approach media production from a perspective that can grasp the changes in the content industry in the Internet era. Building on the tradition of socio-technical change studies, the author traces the factors that shaped the newspaper
industry exploration of electronic media in the 1980s (videotext, teletext, audiotext) and explores how three website projects of US newspapers followed sharply different paths in their definition of the Internet as a new medium. His research is a powerful antidote for the generalized technological
hype that has seduced the industry and the academia for years since the Internet became the dominant solution for digital information delivery. Boczkowski tells three stories of innovation and change which demonstrate that the prophecies of interactivity, hypertext and multimedia are not a
given in news websites: their development depends on organizational, economic, technological and cultural factors that vary from newsroom to newsroom.