bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock
Authors: Link Andreas , Selejan Simina , Maack Christoph , Lenz Monika , Böhm Michael 
Published: December 2008

Abstract
Introduction
Stimulation of beta2-adrenergic receptors (β2-ARs) inhibits tumor necrosis factor-alpha (TNF-α) release in monocytes. In septic shock, endogenous catecholamines induce β2-AR downregulation, leading to an increased TNF-α release. The aims of this study were to analyze the molecular mechanisms of β-adrenergic downregulation and to explore therapeutic interventions with maintained anti-inflammatory efficacy in septic shock using the inhibition of phosphodiesterase 4 (PDE4).

Methods
We conducted in vitro stimulation of peripheral blood mononuclear cells of healthy volunteers (n = 20) and patients with septic shock (n = 20) with lipopolysaccharide (LPS) or Staphylococcus aureus enterotoxin B (SEB) without or with isoprenaline, forskolin (an activator of adenylate cyclase), or ropipram (an inhibitor of PDE4). We also conducted flow cytometric analysis of Toll-like receptor (TLR) 4 and TLR2 surface expression and intracellular TNF-α production of untreated and stimulated CD14+ monocytes. Protein expression of β-ARs, of G proteins, of adenylate cyclase, and of TLRs was measured by Western blotting.

Results
Investigations were done by LPS (100 ng/mL) or SEB (10 ng/mL) when TLR4 and TLR2 were maximally expressed. LPS- or SEB-treated CD14+ monocytes of healthy volunteers were able to produce TNF-α. This effect was attenuated by isoprenaline, forskolin, or rolipram in a concentration-dependent manner. In CD14+ monocytes of patients with septic shock, the anti-inflammatory effect of isoprenaline was completely blunted whereas efficacy of forskolin and rolipram was maintained. CD14+ monocytes of healthy volunteers were compared with patients with septic shock: protein expression of β2-ARs was reduced and inhibitory G protein was increased, whereas no changes in adenylate cyclase and stimulatory G protein were found.

Conclusions
In septic shock, the anti-inflammatory effects of catecholamines are blunted by downregulation of β2-ARs and upregulation of the inhibitory G protein in CD14+ monocytes. Beta-adrenergic downregulation is overcome by inhibitors of PDE4. These results provide a mechanistic rationale for the therapeutic use of selective PDE4 inhibitors in the treatment of septic shock.
Dermatan sulfate proteoglycan biglycan as a potential selectin L/CD44 ligand involved in selective recruitment of peripheral blood CD16(−) natural killer cells into human endometrium
Authors: Kitaya Kotaro , Yasuo Tadahiro 
Published: December 2008

AbstractUnique CD16(−) NK cells acutely increase in the human uterine endometrium after ovulation. The origin of these NK cells remains unknown, but they may be recruited selectively from the circulation. Proteoglycans and their glycosaminoglycan side-chains expressed on endometrial microvascular endothelial cells play a key role in lymphocyte tethering/rolling, the initial step of lymphocyte extravasation. In this study, we sought for the potential proteoglycans involved in tethering/rolling of peripheral blood CD16(−) NK cells on endometrial microvascular endothelial cells. As compared with CD16(+) NK cells and non-NK cells, enriched peripheral blood CD16(−) NK cells bound preferably to immobilized glycosaminoglycans except for keratan sulfate. CD16(−) NK cells bound maximally to dermatan sulfate (DS), which was diminished by enzymatic pretreatment with dermatanase and chondroitinase ABC, but not with chondroitinase ACII. The binding capacity of CD16(−) NK cells to DS was attenuated by blocking antibodies against selectin L and CD44 or pretreatment of CD16(−) NK cells with IL-15. Of three known DS proteoglycans, biglycan and decorin but not epiphycan were expressed in the human cycling endometrium. In the endometrial microvessels, the immunoreactivity for biglycan was greater in the secretory phase than in the proliferative phase, and there was little, if any, immunoreactivity for decorin throughout the menstrual cycle. The ovarian steroid progesterone enhanced biglycan expression in cultured human uterine microvascular endothelial cells. These findings demonstrated that DS proteoglycan biglycan is a potential selectin L/CD44 ligand involved in tethering/rolling of peripheral blood CD16(−) NK cells on endometrial microvascular endothelial cells.
Hypoglycemia with Intensive Insulin Therapy: A Systematic Review and Meta-Analyses of Randomized Trials of Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections
Authors: Fatourechi Mitra M. , Kudva Yogish C. , Murad M. Hassan , Elamin Mohamed B. , Tabini Claudia C. , Montori Victor M. 
Published: December 2008

Abstract
Context: Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear.
Objective: The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia.
Data Sources: We searched electronic databases between 2002 and March 2008.
Study Selection: We selected published randomized trials of CSII vs. MDI.
Data Extraction: Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events.
Data Synthesis: We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, −0.2%; 95% confidence interval (CI), −0.3, −0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificantly fewer minor hypoglycemia episodes per patient per week (−0.08; 95% CI, −0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; Pinteraction = 0.03). Outcomes were not different in patients with type 2 diabetes.
Conclusions: Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data.
Aromatase and 5α-Reductase Inhibition during an Exogenous Testosterone Clamp Unveils Selective Sex Steroid Modulation of Somatostatin and Growth Hormone Secretagogue Actions in Healthy Older Men
Authors: Veldhuis Johannes D. , Mielke Kristi L. , Cosma Mihaela , Soares-Welch Cacia , Paulo Remberto , Miles John M. , Bowers Cyril Y. 
Published: December 2008

Abstract
Background: How endogenous testosterone (Te), 5α-dihydrotestosterone (DHT), and estradiol (E2) regulate pulsatile GH secretion is not understood.
Hypothesis: Conversion of Te to androgenic (Te→DHT) or estrogenic (Te→E2) products directs GH secretion.
Subjects and Location: Healthy older men (N = 42, ages 50–79 yr) participated at an academic medical center.
Methods: We inhibited 5α-reduction with dutasteride and aromatization with anastrozole during a pharmacological Te clamp and infused somatostatin (SS), GHRH, GH-releasing peptide-2 (GHRP-2), and l-arginine/GHRH/GHRP-2 (triple stimulus) to modulate GH secretion.
Endpoints: Deconvolution-estimated basal and pulsatile GH secretion was assessed.
Results: Administration of Te/placebo elevated Te by 2.8-fold, DHT by 2.6-fold, and E2 concentrations by 1.9-fold above placebo/placebo. Te/dutasteride and Te/anastrozole reduced stimulated DHT and E2 by 89 and 86%, respectively. Stepwise forward-selection regression analysis revealed that 1) Te positively determines mean (P = 0.017) and peak (P &lt; 0.001) GH concentrations, basal GH secretion (P = 0.015), and pulsatile GH secretion stimulated by GHRP-2 (P &lt; 0.001); 2) Te and E2 jointly predict GH responses to the triple stimulus (positively for Te, P = 0.006, and negatively for E2, P = 0.031); and 3) DHT correlates positively with pulsatile GH secretion during SS infusion (P = 0.011). These effects persisted when abdominal visceral fat was included in the regression.
Conclusion: The present outcomes suggest a tetrapartite model of GH regulation in men, in which systemic concentrations of Te, DHT, and E2 along with abdominal visceral fat determine the selective actions of GH secretagogues and SS.
Eigenstrain analysis of residual strains and stresses
Authors: Korsunsky A M 
Published: December 2008

Experimental stress evaluation procedures often rely on the measurement of some component(s) of elastic strain followed by point-wise calculation of stress based on continuum elasticity assumptions. Such point-wise assessments are, however, incomplete and not entirely satisfactory, as calculations conducted for different points can easily give rise to values that may not satisfy requirements of global force balance. The real purpose of experimental data interpretation is in fact to obtain a reasonably internally consistent description of the state of stress everywhere in the object to the greatest possible level of detail. What is usually being sought is a residual-stress-admissible (RS-admissible) field, i.e. such that would satisfy boundary conditions imposed both in terms of tractions and displacements, and would correspond to a divergence-free stress field (i.e. such that satisfies stress equilibrium conditions everywhere). Note, however, that elastic strains are no longer required to be compatible. The lack of compatibility of elastic strains arises from the presence of incompatible plastic strains, acting as the origin of residual stresses throughout the object. The present study considers the practical challenge of finding the most probable RS-admissible stress–strain field that corresponds to a set of experimental measurements of residual elastic strains at a number of experimental points. A simple optimization formulation is introduced, and the procedure for finding the unknown underlying distribution of eigenstrains is described. It is then illustrated using examples of one- and two-dimensional residual stress profiles. The implications of this approach are discussed for the analysis of residual stress effects on the durability of engineering structures and assemblies.
Can clinicians benefit from patient satisfaction surveys? Evaluating the NSF for Older People, 2005–2006
Authors: lliffe Steve , Wilcock Jane , Manthorpe Jill , Moriarty Jo , Cornes Michelle , Clough Roger , Bright Les ,   Older People Researching Social Issues (OPRSI)
Published: December 2008

Summary Background A transformation of healthcare is underway, from a sellers' market to a consumers' market, where the satisfaction of the patient's needs is part of the definition of quality. Patient satisfaction surveys are widely used to judge service quality, but clinicians are sceptical about them because they are too often poorly designed measures that do not lead to improvements in the quality of care. Aim To explore the use of patient satisfaction survey data in identifying problems with the provision of inpatient care for older people. Methods A case study using secondary analysis of postal survey data about older people's experiences of health and social care services, obtained during the evaluation of the National Service Framework for Older People in 2005–2006. The survey asked about experiences of inpatient care and of discharge from hospital, and sought perceptions of the avoidability of the admission. Settings and participants A total of 4170 people aged 50 years and over returned a postal questionnaire in six local authority areas of England. Responses from 584 who had experienced a recent overnight stay in hospital are reported and discussed. Findings The response rate was 35%, ranging from 26% to 44% in the six areas surveyed. The great majority of those who had recent direct experience of inpatient care reported that they had been engaged in decision-making, that staff promoted their independence and maintained their dignity. There were widespread examples, however, of the opposite experiences. Discharge from hospital was problematic for about one-third of survey respondents with this experience, and there were different accounts of poorly managed discharges from all areas. Conclusions Case studies using local survey data can be used as formative assessments of services. The response rate to the survey and the likelihood of responder bias mean that patient satisfaction survey data of this sort cannot be used to judge or compare services in a summative way, but can highlight areas where remedial action is needed. Small-scale local surveys may seem to lack the robustness of larger studies, but do identify similar areas of concern. Commissioners and clinicians could use the findings of such surveys to inform dialogues about the quality of hospital care for older people.
Jacques-Louis David’s tumour: an opportunity to study the natural history of a pleomorphic adenoma of the parotid gland
Authors: Wine Humphrey , Baum Michael 
Published: December 2008

Summary The great artist and one-time revolutionary, Jacques-Louis David died in 1825. The cause of his death has been open to speculation. An extraordinary sequence of portraits of the artist describes his transition from handsome middle age to a deformed old man. During this phase a swelling appears at the angle of his left jaw and over a period of 20 years a facial palsy can be diagnosed. We submit that this evidence suggests that malignant transformation of a pleomorphic adenoma of the parotid gland was the proximal cause of his death.
Subsidence of the stem after impaction bone grafting for revision hip replacement using irradiated bone
Authors: Hassaballa M. , Mehendale S. , Poniatowski S. , Kalantzis G. , Smith E. , Learmonth I. D. 
Published: December 2008

Loss of bone stock is a major problem in revision surgery of the hip. Impaction bone grafting of the femur is frequently used when dealing with deficient bone stock. In this retrospective study a consecutive series of 68 patients (69 hips) who had revision of a hip replacement with femoral impaction grafting were reviewed. Irradiated bone allograft was used in all hips. Radiological measurement of subsidence of the stem, incorporation of the graft and remodelling was carried out and showed incorporation of the graft in 26 of 69 hips (38%). However, there was no evidence of trabecular remodelling. Moderate subsidence of 5 mm to 10 mm occurred in ten hips (14.5%), and massive subsidence of > 10 mm in five (7.2%). The results of this study are less favourable than those of others describing studies of revision of the femoral stem using impaction bone grafting. The absence of the characteristic changes of graft remodelling noted in other series raises the question as to whether irradiated bone graft may be a significant factor influencing the post-operative outcome.
The low contact stress mobile-bearing total knee replacement
Authors: Hooper G. , Rothwell A. , Frampton C. 
Published: December 2008

We have examined the outcome of 400 consecutive patients who underwent total knee replacement with the Low Contact Stress mobile-bearing system between 1993 and 1994 and were followed up for a minimum of ten years. All operations were performed by surgeons in Christchurch, New Zealand, who used no other knee prosthesis during the study time. At ten years after operation 238 patients (244 knees) remained for independent clinical and radiological assessment. There was a significant improvement (p < 0.001) in the postoperative knee scores at one, three, seven and ten years, although a slight deterioration in the score occurred between seven and ten years which did not reach statistical significance. The survival for polyethylene wear or loosening was 97% (95% CI 96 to 98) and survival using reoperation for any cause was 92% (95% CI 90 to 94) at 12 years. Polyethylene wear was more common in the meniscal-bearing component, with five knees requiring revision and a further eight demonstrating early wear. Osteolysis was not seen in the rotating platform component, but was present in three of the meniscal-bearing knees. There was no association between the radiological alignment at one year and those knees that subsequently required revision. However, there was an association between the overall limb alignment and the Western Ontario McMasters University score (p < 0.001). The Low Contact Stress mobile-bearing total knee replacement has proved to be a reliable implant at ten years when used in primary knee replacement irrespective of the deformity and diagnosis.
The effect of an associated ulnar styloid fracture on the outcome after fixation of a fracture of the distal radius
Authors: Zenke Y. , Sakai A. , Oshige T. , Moritani S. , Nakamura T. 
Published: December 2008

A total of 118 consecutive patients with a fracture of the distal radius were treated with a volar locking plate; 50 patients had no ulnar styloid fracture, 41 had a basal ulnar styloid fracture, and 27 had a fracture of the tip of the ulnar styloid. There were no significant differences in radiological and clinical results among the three groups. The outcome was good and was independent of the presence of a fracture of the ulnar styloid. A total of five patients (4.2%) had persistent ulnar-sided wrist pain at final follow-up. Nonunion of the ulnar styloid fracture did not necessarily lead to ulnar wrist pain. Patients with persistent ulnar pain had a higher mean initial ulnar variance and increased post-operative loss of ulnar variance. The presence of an associated ulnar styloid fracture of the ulnar styloid does not adversely affect the outcome in patients with a fracture of the distal radius treated by volar plating.
Revision of the humeral component for aseptic loosening in arthroplasty of the shoulder
Authors: Cil A. , Veillette C. J. H. , Sanchez-Sotelo J. , Sperling J. W. , Schleck C. , Cofield R. H. 
Published: December 2008

Between 1976 and 2004, 38 revision arthroplasties (35 patients) were performed for aseptic loosening of the humeral component. The mean interval from primary arthroplasty to revision was 7.1 years (0.4 to 16.6). A total of 35 shoulders (32 patients) were available for review at a mean follow-up of seven years (2 to 19.3). Pre-operatively, 34 patients (97%) had moderate or severe pain; at final follow-up, 29 (83%) had no or only mild pain (p < 0.0001). The mean active abduction improved from 88° to 107° (p < 0.01); and the mean external rotation from 37° to 46° (p = 0.27). Excellent or satisfactory results were achieved in 25 patients (71%) according to the modified Neer rating system. Humeral components were cemented in 29, with ingrowth implants used in nine cases. There were 19 of standard length and 17 were longer (two were custom replacements and are not included). Bone grafting was required for defects in 11 humeri. Only two glenoid components were left unrevised. Intra-operative complications included cement extrusion in eight cases, fracture of the shaft of the humerus is two and of the tuberosity in four. There were four re-operations, one for recurrent humeral loosening, with 89% survival free of re-operations at ten years. Revision surgery for aseptic loosening of the humeral component provides reliable pain relief and modest improvement of movement, although there is a substantial risk of intra-operative complications. Revision to a total shoulder replacement gives better results than to a hemiarthroplasty.
Simultaneous bilateral sequential total knee replacement is as safe as unilateral total knee replacement
Authors: Kim Y.-H. , Choi Y.-W. , Kim J.-S. 
Published: December 2008

We wished to determine whether simultaneous bilateral sequential total knee replacement (TKR) carried increased rates of mortality and complications compared with unilateral TKR in low- and high-risk patients. Our study included 2385 patients who had undergone bilateral sequential TKR under one anaesthetic and 719 who had unilateral TKR. There were no significant pre-operative differences between the groups in terms of age, gender, height, weight, body mass index, diagnosis, comorbidity and duration of follow-up, which was a mean of 10.2 years (5 to 14) in the bilateral and 10.4 years (5 to 14) in the unilateral group. The peri-operative mortality rate (eight patients, 0.3%) of patients who had bilateral sequential TKR was similar to that (five patients, 0.7%) of those undergoing unilateral TKR. In bilateral cases the peri-operative mortality rate (three patients, 0.4%) of patients at high risk was similar to that (five patients, 0.3%) of patients at low risk as it was also in unilateral cases (two patients, 1.0% vs three patients, 0.6%). There was no significant difference (p = 0.735) in either the overall number of major complications between bilateral and unilateral cases or between low- (p = 0.57) and high-risk (p = 0.61) patients. Also, the overall number of minor complications was not significantly different between the bilateral and unilateral group (p = 0.143). Simultaneous bilateral sequential TKR can be offered to patients at low and high risk and has an expected rate of complications similar to that of unilateral TKR.
Applying the International Classification of Functioning, Disability and Health (ICF) to Clinical Practice and Research in Acquired Brain Impairment
Authors: Tate Robyn L. , Perdices Michael 
Published: December 2008

AbstractThe International Classification of Functioning, Disability and Health (ICF) is a taxonomy that classifies health states and health conditions. It is a complex and detailed taxonomy, with 1,424 categories, covering body structures and functions, activities and participation, and environmental factors. The complexity and detail, however, can serve as a barrier in its everyday application. A number of strategies have been developed to facilitate use of the ICF in clinical and research practice, including the development of ‘core sets’. In this article, we present another method which will assist both the newcomer and those more familiar with the ICF. Along with a description of the ICF structure and contents, the article presents a graphical representation of ‘ICF trees’ as a vehicle to more readily grasp the detail of the ICF structure and contents and facilitate its use in the area of acquired brain impairment.