bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Autologous Platelet-rich Plasma to Treat Muscle Strain Injuries
Authors: Hammond Jason W. , Hinton Richard Y. , Curl Leigh Ann , Muriel Joaquin M. , Lovering Richard M.
Published: March 2009

Background

Standard nonoperative therapy for acute muscle strains usually involves short-term rest, ice, and nonsteroidal anti-inflammatory medications, but there is no clear consensus on how to accelerate recovery.

Hypothesis

Local delivery of platelet-rich plasma to injured muscles hastens recovery of function.

Study Design

Controlled laboratory study.

Methods

In vivo, the tibialis anterior muscles of anesthetized Sprague-Dawley rats were injured by a single (large strain) lengthening contraction or multiple (small strain) lengthening contractions, both of which resulted in a significant injury. The tibialis anterior either was injected with platelet-rich plasma, was injected with platelet-poor plasma as a sham treatment, or received no treatment.

Results

Both injury protocols yielded a similar loss of force. The platelet-rich plasma only had a beneficial effect at 1 time point after the single contraction injury protocol. However, platelet-rich plasma had a beneficial effect at 2 time points after the multiple contraction injury protocol and resulted in a faster recovery time to full contractile function. The sham injections had no effect compared with no treatment.

Conclusion

Local delivery of platelet-rich plasma can shorten recovery time after a muscle strain injury in a small-animal model. Recovery of muscle from the high-repetition protocol has already been shown to require myogenesis, whereas recovery from a single strain does not. This difference in mechanism of recovery may explain why platelet-rich plasma was more effective in the high-repetition protocol, because platelet-rich plasma is rich in growth factors that can stimulate myogenesis.

Clinical Relevance

Because autologous blood products are safe, platelet-rich plasma may be a useful product in clinical treatment of muscle injuries.
Confucian Politics and Its Redress: From Radicalism to Gradualism
Authors: Jiande Lu
Published: March 2009

This paper addresses the current revival of Confucianism in China. It analyzes its political issues and outcomes, underlines the possible defects in Confucianism as a theory of politics, i.e., as a science and art of government and a public ethics. It looks back to the dialectical relationship between Confucius and Mencius and shows how the presence of Confucianist elements in 20th-century politics contributed to shape the public and political sphere in contemporary China. The strains between revolutionary and reformist orientations through the last century are still at work in current social movements and reflected in political debates.
Decannulation Following Tracheostomy for Prolonged Mechanical Ventilation
Authors: O'Connor Heidi H. , Kirby Kelly J. , Terrin Norma , Hill Nicholas S. , White Alexander C.
Published: March 2009

Background: We examined the process of decannulation following tracheostomy in patients transferred to a long-term acute care (LTAC) hospital for weaning from prolonged mechanical ventilation (PMV). Methods: A retrospective chart review of 135 patients. Results: Decannulation was successful in 35% of patients a median of 45 days (IQR, 32-76) following tracheostomy. Patients who failed decannulation had a tracheostomy tube placed earlier (14 days; IQR 11-18 vs. 18 days; IQR 14-30, P = .04) and had a shorter length of stay at the acute facility (20 days; IQR, 16-23 vs. 31 days; IQR, 24-45, P = .003) compared with patients who were decannulated. Length of stay and cost of care at the LTAC did not differ with decannulation status. At 3.5 years, 35% (47/135) of all patients and 62% (29/47) of decannulated patients were alive. Conclusions: Decannulation was achieved in 35% of patients transferred to an LTAC for weaning from prolonged mechanical ventilation.
The Effect of Processing on Fiber Dispersion, Fiber Length, and Thermal Degradation of Bleached Sulfite Cellulose Fiber Polypropylene Composites
Authors: Le Baillif Marie , Oksman Kristiina
Published: March 2009

The goal of this study is to examine how the extrusion process affects the dispersion, length, and thermal degradation of cellulose fibers (CF) in polypropylene (PP) composites. Bleached sulfite CF are pelletized and then compounded (20 and 30wt%) in a co-rotating twin screw extruder. The pelletizing process of CF is found to cause extensive fiber breakage. The fiber length is decreased from an initial 1.7 to 0.8 mm. The results show that higher screw speed, higher fiber content, and two extrusions not only increase the shear energy, resulting in improved fiber dispersion but also cause fiber breakage and thermal degradation. The composite's mechanical properties are not improved with better fiber dispersion and the reason for this might be the extensive fiber breakage and thermal degradation. Moreover, it is found that the PP polymer is also slightly degraded during the compounding process.
Enteral and Parenteral Nutrition for the Diabetic Patient: A Case-Based Approach
Authors: McKeever Andrea L. , Fetterman James W.
Published: March 2009

Patients’ nutritional status is essential to ensure beneficial outcomes. However for the diabetic, the caloric energy required is not only sustaining but problematic if not managed appropriately. Uncontrolled hyperglycemia places these patients at risk of complications such as infections, neuropathy, and retinopathy. Health care providers can assist in tailoring nutritional support for diabetic patients. Possible interventions include adjusting caloric requirements to minimize carbohydrates and maximize fat as a main calorie substitute and to suggest appropriate macronutrient sources. Other disease state complications such as diabetic-associated nephropathy and gastroparesis affect nutritional support and present opportunity for further interventions. Diligence regarding blood glucose monitoring is imperative. Additional anti-diabetic therapies can be used to maintain tight glucose control; however, close monitoring must occur to minimize hypoglycemic episodes, which can be life-threatening.
Hepatic Angiomyolipoma and Intramural Small Intestinal Schwannoma: A Coincidence or a Relationship?
Authors: Marsilia Giuseppina Marino , Boscaino Amedeo , La Mura Anna , Ceriello Antonio , De Ritis Rosaria
Published: March 2009

We report a case of hepatic angiomyolipoma associated to a small bowel schwannoma in a 40-years old woman. Both lesions were asyntomatic. Histologically, hepatic angiomyolipoma showed oncocytic features and scanty adipose tissue, the tumor cells expressed desmin, smooth muscle actin, S-100 protein and HMB45. The tumor cells of intramural small intestinal mass were positive for S-100 protein and GFAP and negative for CD117, CD34 and desmin. To the best of our knowledge, no case of hepatic angiomyolipoma has been previously reported in association with intestinal schwannoma.
Mature Solid Teratoma of the Fallopian Tube Mimicking Metastasis of Endometrial Adenocarcinoma: A Case Report
Authors: Roncati Luca , Barbolini Giuseppe , Ghirardini Giuseppe , Rivasi Francesco
Published: March 2009

We report a mature solid teratoma of the fallopian tube in an elderly woman. This mass was noted on CT scan and considered metastatic in nature since following a bioptical diagnosis of endometrial adenocarcinoma. Hysterectomy and bilateral salpingectomy and ovariectomy were performed and a second minor mature solid teratoma was discovered inside the right ovary. Neoplasms of the fallopian tube are very uncommon and this is the first Italian case to be added to about other 60 of the literature. Moreover it joins minimum teratomatous diameter with maximum recorded age.
Endosalpingiosis of the Urinary Bladder: A Case of Probable Implantative Origin With Characterization of Benign Fallopian Tube Immunohistochemistry
Authors: Maniar Kruti P. , Kalir Tamara L. , Palese Michael A. , Unger Pamela D.
Published: March 2009

Müllerianosis of the bladder is an infrequently described lesion consisting of multiple Müllerian-type tissues within the urinary bladder. Few previous cases of pure endosalpingiosis have been described. Here we present a 54-year-old post-menopausal female with a history of prior pelvic surgery with traumatic bladder injury, who was found to have a cystic lesion in the posterior wall of the bladder. Routine histology demonstrated cyst epithelium characteristic of endosalpingiosis. Three benign Fallopian tube specimens were obtained and stained with the relevant immunohistochemical markers for comparison. Results showed an identical immunohistochemical profile between the bladder cyst lining and the normal Fallopian tube controls. This case represents a rare instance of pure endosalpingiosis of the urinary bladder, with a likely implantative origin. This form of bladder Müllerianosis should therefore be considered within the differential diagnosis of cystic lesions of the bladder.
Modification of vincristine dosing during concomitant azole therapy in adult acute lymphoblastic leukemia patients
Authors: Harnicar Stephen , Adel Nelly , Jurcic Joseph
Published: March 2009

Objective. Vincristine is an important component in the treatment of acute lymphoblastic leukemia (ALL) and is now the backbone of therapy in the induction and consolidation phases of this disease. Proper dosing of vincristine is required to maximize disease control while avoiding toxicity. The gastrointestinal toxicity of vincristine such as decreased peristalsis can potentially be increased if the CYP 3A4 enzyme is inhibited. This interaction may become more prevalent with increasing use of CYP 3A4 inhibitors such as the azole antifungals. Since azoles are increasingly being used for prophylaxis and treatment of fungal infections in this patient population, an assessment of vincristine dosing and toxicity is the first step to constructing guidelines for the coadministration of these agents.

Methods. ALL patients !18 years of age receiving vincristine-based therapy from August 2003 through December 2007 with or without azole therapy were included. Data was collected using electronic patient medical records and the pharmacy system (RxTFC). Information was entered into a database for this retrospective study. Patients were separated into two arms; vincristine with azoles and vincristine only. Patient demographic information, chemotherapy regimen, vincristine-induced symptoms, and concurrent strong CYP 3A4 inhibitors and inducers were collected.

Results. A total of 50 patients received vincristine of which 29 (58%) had concurrent azole therapy. No patients received concurrent major CYP 3A4 inhibitors and the baseline characteristics were similar between groups. Vincristine dosing modifications were more common in the azole group (58.6 vs. 23.8%; p = 0.02). The mean dose reduction of vincristine when combined with an azole was 46.5%. Symptoms of decreased peristalsis were more common in patients receiving azoles (65.5 vs. 28.6%; p = 0.019) and on average occurred after the second vincristine dose. Symptoms occurred in 50, 75, and 66.6% of patients receiving fluconazole, voriconazole, and posaconazole, respectively. Patients were more likely to have an incomplete course of vincristine when receiving azole therapy (48.3 vs. 9.5%; p = 0.004).

Conclusion. Caution should be used with the coadministration of vincristine and azoles. It is recommended that institutional guidelines be developed to standardize care for patients receiving vincristine with azole therapy. Potential measures to avoid this interaction include revisiting azole prophylaxis in this patient group and being judicious in azole selection.
Social Support and Homicide
Authors: Worrall John L.
Published: March 2009

This article tests social support theory with a focus on the relationship between general relief payments to the poor and homicide. General relief, a new and untapped measure of social support, represents an improvement on earlier measures of social support, such as welfare spending, because it (a) reflects local priorities, (b) includes both cash grants and in-kind services, and (c) is sufficiently variable at the local level to make it statistically useful. Data from Worrall (2005) were reanalyzed, revealing that general relief was inversely related to homicide, even in the face of various robustness checks.
Abnormalities in brain synchronization are correlated with cognitive impairment in multiple sclerosis
Authors: Arrondo G , Alegre M , Sepulcre J , Iriarte J , Artieda J , Villoslada P
Published: March 2009

Background

Cognitive functions are supported by brain networks and they are highly dependent on the integrity of long white matter tracts that mediate the information flow between such distant cortical areas. Brain damage in multiple sclerosis (MS) may produce cognitive impairment by preferentially damaging these tracts, thereby impairing brain synchrony. Auditory amplitude modulation following responses (AMFR), are oscillatory steady-state responses to rhythmic auditory stimuli that indirectly measure brain synchrony.

Objective

To study the effect of MS lesions in brain synchrony and its relationship with cognitive function.

Methods

We assessed the correlation between cognitive performance, as assessed with the brief repeatable battery–neuropsychology (BRB-N), and the AMFR in a group of 27 MS patients and 22 healthy controls.

Results

The maximal AMFR frequency – but not the amplitude – in the 30–60 Hz range was lower in patients with cognitive impairment than in patients with no cognitive impairment or the healthy controls (39.79 Hz, 43.85 Hz, and 43.84 Hz, respectively, P < 0.05). Indeed, the frequency of the AMFR was negatively correlated with the scores obtained in verbal memory, attention, and executive function. The multiple regression analysis indicates that the AMFR was the best predictor of the BRB-N scores after controlling for potential confounding factors such as age, education, disability, and years of disease evolution.

Conclusions

These results suggest that the loss of synchronization in different central nervous system (CNS) pathways caused by demyelinating lesions might involve both the slowing of brain oscillatory activity and less efficient cognitive processing.
Spontaneous intracerebral hemorrhage in a patient with multiple sclerosis and tumefactive demyelinating lesion
Authors: Stich O , Janowitz D , Rauer S
Published: March 2009

In this report, we discuss the occurrence of intracerebral hemorrhage in a patient with multiple sclerosis during treatment with natalizumab, a humanized monoclonal antibody against the α4β1-integrin. Hemorrhage was located in a previously tumefactive demyelinating lesion. The mechanisms of leukocyte recruitment to the sites of inflammation through interaction of leukocyte α4β1-integrins and endothelial vascular cell adhesion molecule-1 are well known. However, α4β1-integrins are also expressed on endothelial cells and CD34+ bone marrow–derived progenitor cells, controlling several key pathways in angiogenesis. Neovascularization may contribute to tissue repair, particularly in large inflammatory cerebral lesions with increased vascular fragility. We discuss possible interaction of natalizumab with angiogenesis during tissue repair.
Local renin-angiotensin system regulates left ventricular hypertrophy induced by swimming training independent of circulating renin: a pharmacological study
Authors: Oliveira Edilamar M. , Sasaki Maurício S. , Cerêncio Marcela , Baraúna Valério G. , Krieger José E.
Published: March 2009

Introduction.This study addressed the role of the local renin-angiotensin system (RAS) in the left ventricular hypertrophy (LVH) induced by swimming training using pharmacological blockade.

Materials and methods. Female Wistar rats treated with enalapril maleate (60 mg.kg-1.d-1, n=38), losartan (20 mg.kg-1.d-1, n=36) or high salt diet (1% NaCl, n=38) were trained by two protocols (T1: 60-min swimming session, 5 days per week for 10 weeks and T2: the same T1 protocol until the 8thweek, then 9thweek they trained twice a day and 10thweek they trained three times a day). Salt loading prevented activation of the systemic RAS. Haemodynamic parameters, soleus citrate synthase (SCS) activity and LVH (left ventricular/body weight ratio, mg/g) were evaluated.

Results. Resting heart rate decreased in all trained groups. SCS activity increased 41% and 106% in T1 andT2 groups, respectively. LVH was 20% and 30% in T1 andT2 groups, respectively. Enalapril prevented 39% of the LVH in T2 group (p<0.05). Losartan prevented 41% in T1 and 50% inT2 (p<0.05) of the LVH in trained groups. Plasma renin activity (PRA) was inhibited in all salt groups and it was increased in T2 group.

Conclusions.These data provide evidence that the physiological LVH induced by swimming training is regulated by local RAS independent from the systemic, because the hypertrophic response was maintained even when PRA was inhibited by chronic salt loading. However, other systems can contribute to this process.
Association between the angiotensin-converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms and breast cancer among Brazilian women
Authors: Alves Corrêa Silvana Aparecida , Ribeiro de Noronha Samuel Marcos , Nogueira-de-Souza Naiara Correa , Valleta de Carvalho Cristina , Massad Costa Ana Maria , Juvenal Linhares José , Vieira Gomes Mariano Tamura , Guerreiro da Silva Ismael Dale Cotrim
Published: March 2009

Introduction.We evaluated the association between components of the renin-angiotensin system and the development of breast cancer in a case-control study by means of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type 1 (AT1)-receptor A1166C polymorphisms.

Methods. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) or PCR (polymerase chain reaction) using genomic DNA extracted from buccal cells of subjects with (101 cases) or without (307 controls) breast cancer.

Results.The frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, χ2); and for AT1receptor were:AA,AC and CC (in %: cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, χ2).The results suggested that the A1166C polymorphism was not associated with breast cancer risk. On the other hand, for the ACE (I/D), there seemed to be different risks for cancer between cases and controls.

Conclusions.The ID genotype was less frequently associated with the disease than were the DD or II; that is, women with the ID genotype were 3.1 times less likely to develop breast cancer than those with the other genotypes.The ID genotype might be protective against breast cancer and the ACE (I/D) polymorphism a possible target for developing genetic markers for breast cancer.
Role of oxidative stress in the natriuresis induced by central administration of angiotensin II
Authors: Israel Anita , Arzola Jorge , De Jesús Sara , Varela Maider
Published: March 2009

Introduction. Central administration of angiotensin II (Ang II) is known to reduce urinary volume and to increase sodium and potassium excretion. Recently, a novel signalling mechanism for Ang II in the periphery has been shown to involve reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase-derived reactive oxygen species (ROS).Although ROS are now known to be involved in numerous Ang II-regulated processes in peripheral tissues, and are increasingly implicated in CNS neurodegenerative diseases, the role of ROS in central regulation of Ang II-induced hydromineral metabolism remains unexplored.The hypothesis that ROS are involved in central Ang II signalling and in Ang II-dependent antidiuresis, natriuresis and kaliuresis was tested by the use of selective antagonists of the NAD(P)H oxidase cascade. Materials and methods. In intracerebroventricular (ICV)-cannulated rats,Ang II was injected ICV and urinary sodium and potassium excretion was assessed at 1-, 3-, and 6-hour periods of urine collection. Urine sample was analysed for sodium and potassium concentration using a flame photometer. The role of NAD(P)H oxidase-dependent signalling cascade was evaluated using the selective NAD(P)H oxidase inhibitor, apocynin; the superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol); and the protein kinase C inhibitor, chelerythrine. Results. ICV administration of Ang II to conscious hydrated rats resulted in a significant decrease in urinary volume in the first hour, and an increased sodium and potassium excretion during the 6-hour period of urine collection, which was most effective during the 3 and 6 h. Interference with the NAD(P)H oxidase signalling by central administration of apocynin, tempol or chelerythrine, blunted the natriuretic and kaliuretic effect induced by central administration of Ang II, without affecting its antidiuretic action.

Conclusion.This study demonstrates that increases of urinary sodium and potassium excretion elicited by central administration of Ang II are mediated by NAD(P)H oxidase- dependent production of superoxide and protein kinase C activation in conscious hydrated rats.
Inventado: Between Transnational Consumption and the Gardening State in Havana's Urban Spectacle
Authors: Binkley Sam
Published: March 2009

This article presents a theoretically oriented photographic essay on consumer practices and urban spectacle, gathered from a visit to Havana in June of 2006. Employing Zygmunt Bauman's conception of the modern state as a “gardening state,” and other widely theorized depictions of global consumer culture as a force of imaginary investment and ephemerality, the article considers the imbrication of state and market as illustrated in an impressionistic photographic study of everyday urban spectacle in the streets of Havana. The article concludes with a consideration of the plight of everyday Havanans in their effort to improvise survival strategies between the forces of a highly controlling state and a nascent culture in transnational consumerism.
Conservative Treatment of the Cubital Tunnel Syndrome
Authors: SVERNLÖV B. , LARSSON M. , REHN K. , ADOLFSSON L.
Published: March 2009

Conservative treatment of the cubital tunnel syndrome was evaluated in a randomised study of 70 patients with mild or moderate symptoms ( Dellon, 1989 ). All patients were informed about the cause of symptoms and allocated to three groups: night splinting, nerve gliding and control. Evaluation consisted of Canadian Occupational Performance Measure, visual analogue pain scales, strength measurements and neurophysiological examination, before treatment and after six months. Fifty-seven patients were followed for six months. Fifty-one (89.5%) were improved at the follow-up. There were no significant differences between the groups in any of the recorded variables. Night splints and nerve gliding exercises did not add favourably. Routine neurophysiological examination seems unnecessary since 76% of the patients with typical symptoms had normal findings and 75% with pathological findings improved. Patients with mild or moderate symptoms have a good prognosis if they are informed of the causes of the condition and how to avoid provocation.
The Gigogne Flap: An Original Technique for an Optimal Pulp Reconstruction
Authors: BAKHACH J. , GUIMBERTEAU J. C. , PANCONI B.
Published: March 2009

The reconstruction of digital pulp defects is still a challenge in hand surgery. Several reconstructive techniques are available, but in some cases, their advancement capacities are not sufficient for the flap to cover the whole defect. The Gigogne flap is a new, very simple and safe technique. It consists of harvesting two cutaneous flaps successively on the same neurovascular digital palmar bundle. The first plasty may be chosen among the well-known flaps usually applied in pulp reconstruction. The second plasty, the Gigogne flap, is an advancement VY plasty done on the main cutaneous paddle of the first proximal flap. We performed 15 Gigogne flaps in 13 patients, who suffered zone II and III digital pulp amputations. The Gigogne flap increased the advancement capacity of the proximal flap as well as restoring the physiological pulp fatty pad, thus reconstructing a functional and aesthetic fingertip.
Outcome following coronal fractures of the hamate
Authors: Wharton D. M. , Casaletto J. A. , Choa R. , Brown D. J.
Published: March 2009

This is a case series of 14 hamate body fractures, in the coronal plane, with 12 patients having an associated metacarpal injury. Treatment was either conservative or operative and was decided according to the degree of fracture displacement and presence of carpometacarpal subluxation. Patient follow-up was 14.8 months on average, using DASH scores and postoperative radiographs to determine functional and anatomical outcomes. Undisplaced fractures were treated in a cast with good outcome. Postoperative radiographs of patients treated with Kirschner wires for displaced fractures showed incomplete reduction and the outcomes were less favourable. Rigid internal fixation gave excellent radiographic results, although these did not correlate with functional outcome in all patients.
Radial Tunnel Syndrome: Emphasis on the Superficial Branch of the Radial Nerve
Authors: BOLSTER M. A. J. , BAKKER X. R.
Published: March 2009

Reported success rates for decompressing the radial nerve in patients with radial tunnel syndrome vary between 10 and 95%. The combined treatment, releasing both the posterior interosseous nerve and the superficial branch of the radial nerve, has been described only three times, but seems to show more consistent success rates compared with releasing the posterior interosseous nerve alone. We present the results of decompressing the superficial branch of the radial nerve only, the anatomical basis for this approach and a description of the surgical technique. Our results are comparable to the results of the combined treatment. Eleven of 12 patients were satisfied with the results of the operation. This study indicates that pain in patients with radial tunnel syndrome may be treated successfully by surgical decompression of the superficial branch of the radial nerve.
Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase
Authors: Fava Carmen , Kantarjian Hagop M. , Jabbour Elias , O'Brien Susan , Jain Nitin , Rios Mary Beth , Garcia-Manero Guillermo , Ravandi Farhad , Verstovsek Srdan , Borthakur Gautam , Shan Jianqin , Cortes Jorge
Published: March 2009

Second-generation tyrosine kinase inhibitors are effective in Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). Occasionally, patients with Ph+ ALL, or accelerated phase (AP) or blast phase (BP) CML achieve a major cytogenetic response (MCyR) but not a complete hematologic response (CHR). We analyzed 126 patients with CML in AP or BP, or with Ph+ ALL treated with dasatinib or nilotinib after imatinib failure. Twenty patients received sequential treatment with both dasatinib and nilotinib for a total of 146 instances. CHR and MCyR rates were 54% and 37%, respectively in AP, 17% and 39% in BP, and 33% and 50% in Ph+ ALL. Failure to achieve a CHR at the time of achievement of a MCyR was associated with an inferior outcome, similar to that of patients without a MCyR (2-year survival rate, 37% and 35%, respectively). In contrast, patients with MCyR and concomitant CHR had a 77% 2-year survival rate. Twelve of 29 patients with MCyR without concomitant CHR later achieved a CHR; the 2-year survival rate for these patients was 55% compared with 22% for those who never achieved a CHR. These results suggest that achievement of a MCyR without concomitant CHR is associated with poor outcome.
A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis
Authors: Migliori G. B. , Eker B. , Richardson M. D. , Sotgiu G. , Zellweger J-P. , Skrahina A. , Ortmann J. , Girardi E. , Hoffmann H. , Besozzi G. , Bevilacqua N. , Kirsten D. , Centis R. , Lange C.
Published: March 2009

Linezolid is used to treat patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-tuberculosis (TB) cases, although clinical data on its safety, tolerability and efficacy are lacking.

We performed a retrospective, nonrandomised, unblinded observational study evaluating the safety and tolerability of linezolid at 600 mgq.d.orb.i.d.in MDR/XDR-TB treatment in four European countries. Efficacy evaluation compared end-points of 45 linezolid-treated against 110 linezolid-nontreated cases.

Out of 195 MDR/XDR-TB patients, 85 were treated with linezolid for a mean of 221 days. Of these, 35 (41.2%) out of 85 experienced major side-effects attributed to linezolid (anaemia, thrombocytopenia and/or polyneuropathy), requiring discontinuation in 27 (77%) cases. Most side-effects occurred after 60 days of treatment. Twice-daily administration produced more major side-effects than once-daily dosing (p = 0.0004), with no difference in efficacy found. Outcomes were similar in patients treated with/without linezolid (p = 0.8), although linezolid-treated cases had more first-line (p = 0.002) and second-line (p = 0.02) drug resistance and a higher number of previous treatment regimens (4.5versus2.3; p = 0.07).

Linezolid 600 mgq.d.added to an individualised multidrug regimen may improve the chance of bacteriological conversion, providing a better chance of treatment success in only the most complicated MDR/XDR-TB cases. Its safety profile does not warrant use in cases for which there are other, safer, alternatives.
Physiological responses to linear treadmill and cycle ergometer exercise in COPD
Authors: Hsia D. , Casaburi R. , Pradhan A. , Torres E. , Porszasz J.
Published: March 2009

Incremental cardiopulmonary exercise testing work rate ideally increases linearly to the subject’s tolerance within approximately 10 min. Widely used treadmill protocols often yield shorter exercise times in debilitated patients. We compared a recently described treadmill protocol featuring linear work rate increase, weight adjustments anda prioriexercise tolerance estimates with standard cycle and treadmill protocols. We also compared treadmill and cycle responses to examine mechanisms of oxyhaemoglobin desaturation differences.

In total, 16 subjects with chronic obstructive pulmonary disease (COPD; mean±sdforced expiratory volume in 1 s of 36.5±10.9% predicted) performed incremental exercise using cycle, linear treadmill and modified Bruce protocols.

Initial linear treadmill speed and grade yielded oxygen uptake (V′O2) similar to cycle unloaded pedalling; Bruce protocol first stage elicited much higherV′O2. Exercise duration was much shorter in Bruce than in cycle or linear treadmill protocols. At peak exercise, greater desaturation was noted in linear treadmill and Bruce protocols compared with cycle (-8.9±4.9versus-8.5±4.7versus-3.7±3.3%; p<0.001); at iso-V′O2values this difference widened as exercise proceeded. Iso-V′O2desaturation differences were largely related to higher ventilatory response to cycle than to treadmill exercise.

The linear incremental treadmill protocol generates responses similar to cycle ergometry in severe COPD. However, cycle ergometry elicits less desaturation than does ambulation, making the linear treadmill protocol advantageous when evaluating COPD patients.
Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD
Authors: Klagas I. , Goulet S. , Karakiulakis G. , Zhong J. , Baraket M. , Black J. L. , Papakonstantinou E. , Roth M.
Published: March 2009

Glycosaminoglycans (GAG) are essential extracellular matrix molecules which regulate tissue flexibility, a parameter that is reduced in airways of patients with asthma and chronic obstructive pulmonary disease (COPD). We investigated the expression of GAG and their metabolising enzymes in primary human airway smooth muscle cells (ASMC) obtained from healthy donors (controls) and patients with asthma or COPD.

Total GAG synthesis was assessed by [3H]-glucosamine incorporation. GAG were isolated, purified, fractionated by electrophoresis and characterised using specific GAG-degrading enzymes. Secretion of hyaluronic acid (HA) by ASMC from patients with asthma or COPD was significantly decreased compared with controls. RT-PCR analysis and western blotting revealed that this decrease was associated with a significant reduction in the expression of HA synthase-1 and -2 and a significant increase of hyaluronidase-1. Furthermore, the expression of the HA receptor CD44 was significantly decreased, whereas the receptor for HA-mediated motility was not expressed in asthma or COPD.

Our results indicate that there is a decreased expression of HA in asthma and COPD associated with a synergistic regulation of HA metabolising enzymes that may regulate the pathological airway remodelling in these lung diseases.
Informed participation in a randomised controlled trial of computed tomography screening for lung cancer
Authors: van den Bergh K. A. M. , Essink-Bot M. L. , van Klaveren R. J. , de Koning H. J.
Published: March 2009

The actual lung cancer (screening) knowledge, attitudes, risk perceptions, reasons to participate in or decline participation, and informed decisions of subjects who decided to or decided not to participate in the Dutch-Belgian randomised controlled trial for lung cancer screening in high-risk subjects (the NELSON trial) were evaluated.

A total of 2,500 high-risk subjects were asked to complete a questionnaire 3 weeks after they had received a brochure with information about the trial. Differences in knowledge, attitude and risk perception between participants and nonparticipants were analysed with logistic regression analyses adjusted for sex and smoking status.

The questionnaire response of trial participants was 80% (n = 889) whereas the response of nonparticipants was low (7%, n = 97) and selective. Participants' responses to knowledge items on lung cancer as a disease were on average more often correct (mean±sd68±17%) than items on lung cancer screening (49±29%). Participants had adequate knowledge on lung cancer screening (51%) more often than the nonparticipants (38%; p = 0.009). Of the decisions regarding participation, 49% were uninformed, mainly due to insufficient knowledge. Most of the participants (99%) and 64% of the nonparticipants had a positive attitude towards lung cancer screening.

Additional efforts are required to improve the knowledge and understanding of subjects who are in the process of decision-making regarding participation in a lung cancer screening trial.
Reliability of ventilatory parameters during cycle ergometry in multicentre trials in COPD
Authors: O’Donnell D. E. , Travers J. , Webb K. A. , He Z. , Lam Y-M. , Hamilton A. , Kesten S. , Maltais F. , Magnussen H.
Published: March 2009

We studied the distribution profiles and repeatability of key exercise performance parameters in the first large multicentre trials to include these measurements in chronic obstructive pulmonary disease (COPD).

After a screening visit, 463 subjects with COPD (mean±sdforced expiratory volume in 1 s 43±13% predicted) completed two run-in visits before treatment randomisation. At the run-in visits, measurements were conducted at rest, at a standardised time near end-exercise (isotime) and at peak exercise during constant work rate (CWR) cycle tests at 75% of each individual’s maximum work capacity. The intraclass correlation coefficient was used to evaluate the test-retest repeatability of measurements of endurance time (ET), inspiratory capacity (IC), ventilation and dyspnoea intensity (Borg scale) during exercise.

IC, ventilation and dyspnoea ratings were normally distributed; ET showed rightward skew (median<mean, skewness of 10.9 (much greater than zero)) with 16% of the sample exceeding 1 sdof the mean. ET was highly repeatable across run-in visits: 7.9±4.8 and 8.4±5.1 min (R = 0.84). IC values at rest, isotime and peak exercise were all highly repeatable (R≥0.87). Ventilation was repeatable over the same time-points (R≥0.92), as was dyspnoea intensity at isotime (R = 0.79) and at peak exercise (R = 0.81).

In conclusion, key perceptual and ventilatory parameters can be reliably measured during CWR cycle exercise in multicentre clinical trials in moderate to very severe COPD.
Mechanisms of the noxious inflammatory cycle in cystic fibrosis
Authors: Rottner Mathilde , Freyssinet Jean-Marie , Martínez M Carmen
Published: March 2009

Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508), accounting for this pathology, is retained in the endoplasmic reticulum (ER), induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis.
Missing call bias in high-throughput genotyping
Authors: Fu Wenqing , Wang Yi , Wang Ying , Li Rui , Lin Rong , Jin Li
Published: March 2009

Background

The advent of high-throughput and cost-effective genotyping platforms made genome-wide association (GWA) studies a reality. While the primary focus has been invested upon the improvement of reducing genotyping error, the problems associated with missing calls are largely overlooked.

Results

To probe into the effect of missing calls on GWAs, we demonstrated experimentally the prevalence and severity of the problem of missing call bias (MCB) in four genotyping technologies (Affymetrix 500 K SNP array, SNPstream, TaqMan, and Illumina Beadlab). Subsequently, we showed theoretically that MCB leads to biased conclusions in the subsequent analyses, including estimation of allele/genotype frequencies, the measurement of HWE and association tests under various modes of inheritance relationships. We showed that MCB usually leads to power loss in association tests, and such power change is greater than what could be achieved by equivalent reduction of sample size unbiasedly. We also compared the bias in allele frequency estimation and in association tests introduced by MCB with those by genotyping errors. Our results illustrated that in most cases, the bias can be greatly reduced by increasing the call-rate at the cost of genotyping error rate.

Conclusion

The commonly used 'no-call' procedure for the observations of borderline quality should be modified. If the objective is to minimize the bias, the cut-off for call-rate and that for genotyping error rate should be properly coupled in GWA. We suggested that the ongoing QC cut-off for call-rate should be increased, while the cut-off for genotyping error rate can be reduced properly.
Discovering genes associated with dormancy in the monogonont rotifer Brachionus plicatilis
Authors: Denekamp Nadav Y , Thorne Michael AS , Clark Melody S , Kube Michael , Reinhardt Richard , Lubzens Esther
Published: March 2009

Background

Microscopic monogonont rotifers, including the euryhaline species Brachionus plicatilis, are typically found in water bodies where environmental factors restrict population growth to short periods lasting days or months. The survival of the population is ensured via the production of resting eggs that show a remarkable tolerance to unfavorable conditions and remain viable for decades. The aim of this study was to generate Expressed Sequence Tags (ESTs) for molecular characterisation of processes associated with the formation of resting eggs, their survival during dormancy and hatching.

Results

Four normalized and four subtractive libraries were constructed to provide a resource for rotifer transcriptomics associated with resting-egg formation, storage and hatching. A total of 47,926 sequences were assembled into 18,000 putative transcripts and analyzed using both Blast and GO annotation. About 28–55% (depending on the library) of the clones produced significant matches against the Swissprot and Trembl databases. Genes known to be associated with desiccation tolerance during dormancy in other organisms were identified in the EST libraries. These included genes associated with antioxidant activity, low molecular weight heat shock proteins and Late Embryonic Abundant (LEA) proteins. Real-time PCR confirmed that LEA transcripts, small heat-shock proteins and some antioxidant genes were upregulated in resting eggs, therefore suggesting that desiccation tolerance is a characteristic feature of resting eggs even though they do not necessarily fully desiccate during dormancy. The role of trehalose in resting-egg formation and survival remains unclear since there was no significant difference between resting-egg producing females and amictic females in the expression of the tps-1 gene. In view of the absence of vitellogenin transcripts, matches to lipoprotein lipase proteins suggest that, similar to the situation in dipterans, these proteins may serve as the yolk proteins in rotifers.

Conclusion

The 47,926 ESTs expand significantly the current sequence resource of B. plicatilis. It describes, for the first time, genes putatively associated with resting eggs and will serve as a database for future global expression experiments, particularly for the further identification of dormancy related genes.
Differential patterns of reactive oxygen species and antioxidative mechanisms during atrazine injury and sucrose-induced tolerance in Arabidopsis thaliana plantlets
Authors: Ramel Fanny , Sulmon Cécile , Bogard Matthieu , Couée Ivan , Gouesbet Gwenola
Published: March 2009

Background

Besides being essential for plant structure and metabolism, soluble carbohydrates play important roles in stress responses. Sucrose has been shown to confer to Arabidopsis seedlings a high level of tolerance to the herbicide atrazine, which causes reactive oxygen species (ROS) production and oxidative stress. The effects of atrazine and of exogenous sucrose on ROS patterns and ROS-scavenging systems were studied. Simultaneous analysis of ROS contents, expression of ROS-related genes and activities of ROS-scavenging enzymes gave an integrative view of physiological state and detoxifying potential under conditions of sensitivity or tolerance.

Results

Toxicity of atrazine could be related to inefficient activation of singlet oxygen (1O2) quenching pathways leading to 1O2 accumulation. Atrazine treatment also increased hydrogen peroxide (H2O2) content, while reducing gene expressions and enzymatic activities related to two major H2O2-detoxification pathways. Conversely, sucrose-protected plantlets in the presence of atrazine exhibited efficient 1O2 quenching, low 1O2 accumulation and active H2O2-detoxifying systems.

Conclusion

In conclusion, sucrose protection was in part due to activation of specific ROS scavenging systems with consequent reduction of oxidative damages. Importance of ROS combination and potential interferences of sucrose, xenobiotic and ROS signalling pathways are discussed.
Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)
Authors: van den Broek Frank JC , de Graaf Eelco JR , Dijkgraaf Marcel GW , Reitsma Johannes B , Haringsma Jelle , Timmer Robin , Weusten Bas LAM , Gerhards Michael F , Consten Esther CJ , Schwartz Matthijs P , Boom Maarten J , Derksen Erik J , Bijnen A Bart , Davids Paul HP , Hoff Christiaan , van Dullemen Hendrik M , Heine G Dimitri N , van der Linde Klaas , Jansen Jeroen M , Mallant-Hent Rosalie CH , Breumelhof Ronald , Geldof Han , Hardwick James CH , Doornebosch Pascal G , Depla Annekatrien CTM , Ernst Miranda F , van Munster Ivo P , de Hingh Ignace HJT , Schoon Erik J , Bemelman Willem A , Fockens Paul , Dekker Evelien
Published: March 2009

Background

Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications.

The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas.

Methods/design

Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma ≥ 3 cm, located between 1–15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment.

Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures.

Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group.

Discussion

The TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas.

Trial registration number

(trialregister.nl) NTR1422