bluuebunny/crossref_metadata_2025 huggingface dataset:
Neoadjuvant FOLFOX chemotherapy in 34 consecutive patients with mucinous peritoneal carcinomatosis of appendiceal origin
Authors: Sugarbaker Paul H. , Bijelic Lana , Chang David , Yoo Dal
Published: August 2010

Background

A treatment option for patients with peritoneal mucinous carcinomatosis (PMCA) from an appendiceal neoplasm is cytoreductive surgery and perioperative intraperitoneal chemotherapy. Also, these patients are recommended for systemic chemotherapy using an oxaliplatin and 5‐fluorouracil (FOLFOX) regimen. A major question concerns the proper timing (neoadjuvant vs. adjuvant) of the systemic chemotherapy.

Methods

In January of 2005 a prospective study was initiated to routinely treat patients with peritoneal dissemination of a mucinous adenocarcinoma of the appendix with neoadjuvant chemotherapy using FOLFOX. All patients had a clinical, CT, intraoperative, and histopathological assessment of chemotherapy effects. The study was closed in July of 2009.

Results

Thirty‐four consecutive patients were available for evaluation. In the clinical evaluation and CT evaluation, 24 (71%) and 22 (65%), respectively, had stable disease on chemotherapy. By intraoperative examination 17 (50%) patients were observed to have progressed. By histopathology seven had a partial response and three patients a complete response (29%).

Conclusions

In these carcinomatosis patients clinical and CT assessment of response to neoadjuvant chemotherapy seldom provided useful data over this short time period. Intraoperative findings indicated progression in 50% of patients. By histopathology, 29% of patients had a response. J. Surg. Oncol. 2010;102:576–581. © 2010 Wiley‐Liss, Inc.
Optimizing resection for “responding” hepatic metastases after neoadjuvant chemotherapy
Authors: Thomay Alan A. , Charpentier Kevin P.
Published: August 2010

Fifty percent of patients with colorectal cancer will develop metastases at some time during their disease, with the liver being the most common site. Recent advances in the treatment of metastatic colorectal cancer have led to a change in treatment paradigm. What follows is a review of the surgical management of hepatic colorectal metastases responding to neoadjuvant chemotherapy. In addition, the complexity of treating patients with “disappearing” colorectal liver metastases is discussed. J. Surg. Oncol. 2010;102:1002–1008. © 2010 Wiley‐Liss, Inc.
In vitro investigation of the biological effects associated with human dermal fibroblasts exposed to 2.52 THz radiation
Authors: Wilmink Gerald J. , Rivest Benjamin D. , Roth Caleb C. , Ibey Bennett L. , Payne Jason A. , Cundin Luisiana X. , Grundt Jessica E. , Peralta Xomalin , Mixon Dustin G. , Roach William P.
Published: August 2010

Background

Terahertz (THz) radiation sources are increasingly being used in military, defense, and medical applications. However, the biological effects associated with this type of radiation are not well characterized. In this study, we evaluated the cellular and molecular response of human dermal fibroblasts exposed to THz radiation.

Methods

In vitro exposures were performed in a temperature‐controlled chamber using a molecular gas THz laser (2.52 THz, 84.8 mW cm−2, durations: 5, 10, 20, 40, or 80 minutes). Both computational and empirical dosimetric techniques were conducted using finite‐difference time‐domain (FDTD) modeling approaches, infrared cameras, and thermocouples. Cellular viability was assessed using conventional MTT assays. In addition, the transcriptional activation of protein and DNA sensing genes were evaluated using qPCR. Comparable analyses were also conducted for hyperthermic and genotoxic positive controls.

Results

We found that cellular temperatures increased by 3°C during all THz exposures. We also found that for each exposure duration tested, the THz and hyperthermic exposure groups exhibited equivalent levels of cell survival (≥90%) and heat shock protein expression (∼3.5‐fold increases). In addition, the expression of DNA sensing and repair genes was unchanged in both groups; however, appreciable increases were observed in the genotoxic controls.

Conclusions

Human dermal fibroblasts exhibit comparable cellular and molecular effects when exposed to THz radiation and hyperthermic stress. These findings suggest that radiation at 2.52 THz generates primarily thermal effects in mammalian cells. Therefore, we conclude that THz‐induced bioeffects may be accurately predicted with conventional thermal damage models. Lasers Surg. Med. 42:152–163, 2011 © 2010 Wiley‐Liss, Inc.
The Matrix‐Binding Domain of Microfibril‐Associated Glycoprotein‐1 Targets Active Connective Tissue Growth Factor to a Fibroblast‐Produced Extracellular Matrix
Authors: Weinbaum Justin S. , Tranquillo Robert T. , Mecham Robert P.
Published: August 2010

It is advantageous to use biomaterials in tissue engineering that stimulate extracellular matrix (ECM) production by the cellular component. Connective tissue growth factor (CTGF) stimulates type I collagen (COL1A1) transcription, but is functionally limited as a free molecule. Using a matrix‐binding domain (MBD) from microfibril‐associated glycoprotein‐1, the fusion protein MBD–CTGF was targeted to the ECM and tested for COL1A1 transcriptional activation. MBD–CTGF produced by the ECM‐synthesizing fibroblasts, or provided exogenously, localized to the elastic fiber ECM. MBD–CTGF, but not CTGF alone, led to a two‐fold enhancement of COL1A1 expression. This study introduces a targeting technology that can be used to elevate collagen transcription in engineered tissues and thereby improve tissue mechanics.

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Establishment of an orthotopic transplantable gastric cancer animal model for studying the immunological effects of new cancer therapeutic modules
Authors: Shan Yan‐Shen , Fang Jung‐Hua , Lai Ming‐Derg , Yen Meng‐Chi , Lin Pin‐Wen , Hsu Hui‐Ping , Lin Chian‐Yuh , Chen Yi‐Ling
Published: August 2010

Tumor cell growth is influenced by the cellular microenvironment including the presence of immune cells and blood vessels. Currently, no transplantable gastric cancer syngeneic animal models exist; therefore, we set out to establish a mouse gastric carcinoma cell line, which was named mouse gastric carcinoma cell line 3I (MGCC3I), from forestomach carcinoma developed in benzo[a]pyrene‐treated ICR mice. MGCC3I cells showed epithelial‐like morphology, multinuclear giant cell formation, and retained an intestinal phenotype, which are similar to human gastric cancer carcinoma cells. The expression of gastric cancer markers MUC1, MUC2, and MUC5AC, and oncogenes c‐myc, c‐met, cyclin E1, and cancer stem cell marker CD44 was determined in MGCC3I cells. MGCC3I cells formed poorly differentiated stomach tumors following orthotopic implantation into the stomachs of syngeneic ICR mice. Histone deacetylase inhibitors are recognized as a new class of anticancer drugs. The immunological therapeutic effects of the histone deacetylase inhibitors sodium butyrate and valproic acid were evaluated in this new animal tumor model. Sodium butyrate inhibited MGCC3I stomach tumor formation in animal models. Increased tumor infiltration by CD8 T cells and neutrophils was observed in mice treated with sodium butyrate or valproic acid. Depletion of CD8 T cells significantly attenuated tumor regression mediated by histone deacetylase inhibitors, which is correlated with enhancement of the MHC class I pathway in MGCC3I cells. Taken together, we have successfully established an orthotopic transplantable gastric tumor animal model and demonstrated its usefulness in revealing the role of CD8 T cells in the therapeutic effects of sodium butyrate. © 2010 Wiley‐Liss, Inc.
Long‐term effects of coordinative training in degenerative cerebellar disease
Authors: Ilg Winfried , Brötz Doris , Burkard Susanne , Giese Martin A. , Schöls Ludger , Synofzik Matthis
Published: August 2010

Few clinical studies have evaluated physiotherapeutic interventions for patients with degenerative cerebellar disease. In particular, evidence for long‐term effects and transfer to activities of daily life is rare. We have recently shown that coordinative training leads to short‐term improvements in motor performance. To evaluate long‐term benefits and translation to real world function, we here assessed motor performance and achievements in activities of daily life 1 year after a 4 week intensive coordinative training, which was followed by a home training program. Effects were assessed by clinical rating scales, a goal attainment score and quantitative movement analysis. Despite gradual decline of motor performance and gradual increase of ataxia symptoms due to progression of disease after 1 year, improvements in motor performance and achievements in activities of daily life persisted. Thus, also in patients with degenerative cerebellar disease, continuous coordinative training leads to long‐term improvements, which translate to real world function. © 2010 Movement Disorder Society
Prevalence and clinical profile of restless legs syndrome in Parkinson's disease
Authors: Verbaan Dagmar , van Rooden Stephanie M. , van Hilten Jacobus J. , Rijsman Roselyne M.
Published: August 2010

Parkinson's disease (PD) and restless legs syndrome (RLS) have a dopaminergic link. More insight in the clinical profile of RLS in patients with PD may benefit our understanding of this link. The aims of this study were to evaluate the frequency and clinical profile of RLS in a large cohort of PD patients. In 269 nondemented Caucasian PD patients, the four diagnostic criteria for RLS were administered by a RLS trained researcher. In patients with definite RLS, the severity of these symptoms was assessed. Furthermore, in all patients, relevant motor and nonmotor symptoms in PD were evaluated. Definite RLS was present in 11% of the patients. RLS patients were more often female (69% vs. 32%, P < 0.001), but no other significant differences existed between PD patients with and without RLS. Within the PD patients with RLS, severity of RLS correlated positively with PD severity, motor fluctuations, depressive symptoms, daytime sleepiness, cognitive problems, autonomic symptoms, and psychotic symptoms. This study in a large PD cohort shows that prevalence of RLS is similar to that in the general population, which might be caused by underestimation of RLS due to dopaminergic treatment. No relations were found between the presence of RLS and PD symptoms, but the severity of RLS was related to the severity of PD‐related, mainly nondopaminergic, symptoms. It is hypothesized that, nondopaminergic systems, such as the noradrenergic system may play a role in the possible link between PD and RLS. © 2010 Movement Disorder Society
Psychiatric symptoms associated with focal hand dystonia
Authors: Voon Valerie , Butler Tracy R. , Ekanayake Vindhya , Gallea Cecile , Ameli Rezvan , Murphy Dennis L. , Hallett Mark
Published: August 2010

Myoclonus dystonia and idiopathic dystonia are associated with a greater frequency of obsessive compulsive disorder (OCD) and major depression. We investigated the frequency of OCD in 39 patients with primary focal hand dystonia (FHD) using a semistructured interview. OCD and subsyndromal OCD was diagnosed in 5 of 39 (12.82%) patients with FHD, whereas OCD occurs in 2.3% of the general population. Recurrent depression occurred in (7 of 39) 17.95% of patients with FHD along with a family history of depression in (16 of 39) 41.02%. Overlapping mechanisms manifesting as FHD may also predispose to OC symptoms and likely implicates a common striatal dysfunction. © 2010 Movement Disorder Society
Meta‐analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications
Authors: Naumann Markus , Carruthers Alastair , Carruthers Jean , Aurora Sheena K. , Zafonte Ross , Abu‐Shakra Susan , Boodhoo Terry , Miller‐Messana Mary Ann , Demos George , James Lynn , Beddingfield Frederick , VanDenburgh Amanda , Chapman Mary Ann , Brin Mitchell F.
Published: August 2010

This meta‐analysis evaluated the frequency of neutralizing antibody (nAb) conversion with onabotulinumtoxinA (BOTOX®; Allergan) across five studied indications. The analysis was based on large, controlled or prospective, open‐label trials (durations 4 months to ≥2 years). Serum samples were analyzed for nAbs using the Mouse Protection Assay. Subjects who were antibody negative at baseline and had at least one analyzable postbaseline antibody assay result were included. The 16 clinical studies included 3,006 subjects; of these, 2,240 met the inclusion criteria for this analysis. Subjects received 1–15 treatments (mean 3.8 treatments) with onabotulinumtoxinA. Total doses per treatment cycle ranged from 10 or 20 units in glabellar lines to 20–500 units in cervical dystonia. The numbers of subjects who converted from an antibody‐negative status at baseline to antibody‐positive status at any post‐treatment time point were: cervical dystonia 4/312 (1.28%), glabellar lines 2/718 (0.28%), overactive bladder 0/22 (0%), post‐stroke spasticity 1/317 (0.32%), and primary axillary hyperhidrosis 4/871 (0.46%). Across all indications, 11/2,240 subjects (0.49%) converted from antibody negative at baseline to positive at one or more post‐treatment time points, but only three subjects became clinically unresponsive to onabotulinumtoxinA at some point following a positive assay. Based on these large trials, the frequency of antibody conversion after onabotulinumtoxinA treatment is very low, and infrequently leads to loss of efficacy. © 2010 Movement Disorder Society
Restless legs syndrome and Parkinson's disease in men
Authors: Gao Xiang , Schwarzschild Michael A. , O'Reilly Eilis J. , Wang Hao , Ascherio Alberto
Published: August 2010

We examined whether men with restless legs syndrome (RLS) have a higher prevalence of Parkinson's disease (PD) among 23,119 US participants of the Health Professional Follow‐up Study who were free of diabetes and arthritis. RLS was assessed using a set of standardized questions recommended by the International RLS Study Group. PD cases were identified by self‐reported questionnaires and confirmed by review of medical records. Compared to men without RLS, multivariate‐adjusted odds ratios for PD were 1.1 (95% confidence interval: 0.4, 3.0) for men with RLS symptoms 5–14 times per month and 3.09 (95% confidence interval: 1.5, 6.2; P trend = 0.003) for those with symptoms 15 times or more per month, after adjusting for age, smoking, use of antidepressant, and other covariates. In conclusion, men with RLS are more likely to have concurrent PD. Prospective studies are warranted to clarify the temporal relationship between RLS and PD. © 2010 Movement Disorder Society
Incidence of Parkinson's disease among hospital patients with methamphetamine‐use disorders
Authors: Callaghan Russell C. , Cunningham James K. , Sajeev Gautam , Kish Stephen J.
Published: August 2010

Because methamphetamine exposure to experimental animals can damage brain dopamine neurones, we examined whether hospital patients diagnosed with methamphetamine‐related disorders might have greater risk of subsequent admission with a Parkinson's disease diagnosis. This was a population‐based cohort study using all statewide inpatient hospital discharge records from July 1, 1990, through June 30, 2000, in California, USA, in which subjects aged at least 50 years were followed for up to 10 years. Individuals with reported methamphetamine‐related conditions (n = 1,863; ICD‐9 codes 304.4, 305.7, 969.7, and E854.2) were matched on demographic variables and follow‐up time with those with primary appendicitis conditions (n = 9,315). The appendicitis group had a Parkinson's disease incidence rate no different than the rate found among members of a large health maintenance organization in California. Cox regression procedures were used to estimate group differences in the rates of receiving a subsequent inpatient diagnosis of Parkinson's disease (ICD‐9 332.0). The methamphetamine group showed increased risk of a subsequent admission with Parkinson's disease compared with that of the matched appendicitis group (adjusted hazard ratio = 2.65, 95% CI, 1.17–5.98, P= 0.019). Study limitations include a population limited to hospital admissions, an uncertainty regarding diagnostic validity of the ICD‐9 code 332.0 (Parkinson's disease), and a small number of incident cases with suspected Parkinson's disease. We strongly emphasize the preliminary nature of the findings. Nevertheless, these data, requiring replication, provide some evidence that methamphetamine users might be at greater than normal risk for developing Parkinson's disease. © 2010 Movement Disorder Society
The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: A randomized, double‐blind, placebo‐controlled study
Authors: Pal Endre , Nagy Ferenc , Aschermann Zsuzsanna , Balazs Eva , Kovacs Norbert
Published: August 2010

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. © 2010 Movement Disorder Society
Falls in Parkinson's disease: Kinematic evidence for impaired head and trunk control
Authors: Cole Michael H. , Silburn Peter A. , Wood Joanne M. , Worringham Charles J. , Kerr Graham K.
Published: August 2010

Changes in stride characteristics and gait rhythmicity characterize gait in Parkinson's disease and are widely believed to contribute to falls in this population. However, few studies have examined gait in PD patients who fall. This study reports on the complexities of walking in PD patients who reported falling during a 12‐month follow‐up. Forty‐nine patients clinically diagnosed with idiopathic PD and 34 controls had their gait assessed using three‐dimensional motion analysis. Of the PD patients, 32 (65%) reported at least one fall during the follow‐up compared with 17 (50%) controls. The results showed that PD patients had increased stride timing variability, reduced arm swing and walked with a more stooped posture than controls. Additionally, PD fallers took shorter strides, walked slower, spent more time in double‐support, had poorer gait stability ratios and did not project their center of mass as far forward of their base of support when compared with controls. These stride changes were accompanied by a reduced range of angular motion for the hip and knee joints. Relative to walking velocity, PD fallers had increased mediolateral head motion compared with PD nonfallers and controls. Therefore, head motion could exceed “normal” limits, if patients increased their walking speed to match healthy individuals. This could be a limiting factor for improving gait in PD and emphasizes the importance of clinically assessing gait to facilitate the early identification of PD patients with a higher risk of falling. © 2010 Movement Disorder Society
A mouse model for sleeve gastrectomy: Applications for diabetes research
Authors: Schlager Avraham , Khalaileh Abed , Mintz Yoav , Gazala Mahmoud Abu , Globerman Anat , Ilani Nadav , Rivkind Avraham I. , Salpeter Seth , Dor Yuval , Zamir Gideon
Published: August 2010

Introduction.

Discovery of enhanced glucose tolerance following bariatric surgery has sparked renewed interest in the investigation of unchartered underlying pathways of glucose homeostasis. Delineation of this pathway may ultimately be the first step in the creation of a novel therapy for type II diabetes. Nevertheless, the technical complexity and formidable nature of these surgeries coupled with the fragile nature of small rodents has made the creation of a mouse model to study these effects incredibly challenging. We have created a simplified sleeve gastrectomy mouse model to study the effects of bariatric surgery on glucose tolerance and beta cell proliferation.

Methods.

Nineteen mice were randomized to undergo either sleeve gastrectomy (SG) (9) or sham operation (SH) (10). Weight and serum glucose were measured three times weekly and serum insulin measurements and pancreatic harvest were performed at the time of sacrifice. Five mice from each group were sacrificed after one week and the remainder sacrificed after one month.

Results.

Survival of mice was 100% for both groups. The SG group demonstrated an initial drop in weight and serum glucose as compared to SH, which normalized by one month following surgery. Serum insulin levels and rate of beta cell proliferation were similar in both groups after one week and one month.

Conclusion.

The simplified sleeve gastrectomy is a technically straightforward, low‐mortality technique for creating a bariatric mouse model which most faithfully replicates bariatric surgery performed in humans. This model can be a valuable tool to investigate the glucose tolerance and beta cell effects of bariatric surgery. © 2010 Wiley‐Liss, Inc. Microsurgery, 2011.
Antegrade anterolateral thigh perforator flap advancement for soft‐tissue reconstruction of the knee: Case report
Authors: Fujiwara Takashi , Chen Chien‐Chang , Ghetu Nicolae , Jeng Seng‐Feng , Kuo Yur‐Ren
Published: August 2010

Reconstruction of soft‐tissue defects of the knee has always been a challenging task to the plastic surgeon. In some cases, local or regional flaps are too small or have limited arc of rotation for adequate coverage. Free flaps can be technically demanding and time consuming. We report for the first time an antegrade anterolateral thigh perforator flap advancement, used to reconstruct the knee soft tissue defect in a 54‐year‐old man. The operative procedure required skeletonizing the perforators of anterolateral thigh flap and advancing the flap in the defect. The postoperative course was uneventful with the patient returned to normal daily activity and full range of motion 3‐months postoperatively. The shorter operating time with decreased donor‐site morbidity make this flap as a valuable alternative for soft‐tissue reconstruction of the knee. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
Composite skull and dura defect reconstruction using combined latissimus dorsi musculocutaneous and serratus anterior muscle‐rib free flap coupled with vascularized galea transfer: A case report
Authors: Lee Jing‐Wei , Hsueh Yuan‐Yu , Lee Jung‐Shun
Published: August 2010

Recalcitrant epidural abscess following cranioplasty is a complicated problem, which becomes even more trying when large span of dura and skull bone are being replaced by alloplastic materials. A 22‐year‐old male underwent right fronto‐temporo‐parietal craniectomy and duroplasty with artificial dura graft after traumatic brain injury. Epidural abscesses recurred after cranioplasty with autologous bone graft as well as with a methyl methacrylate bone plate. The massive defects of both the dura and skull bone (15 × 9 cm) caused by radical debridement were reconstructed successfully with a combined free latissimus dorsi and serratus anterior myo‐osseous flap transfer plus galea flap transposition. Proper contour and adequate stability of the construct were maintained during 2‐year follow up without episodes of relapsing infection. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
Modern adjuncts and technologies in microsurgery: An historical and evidence‐based review
Authors: Pratt George F. , Rozen Warren M. , Chubb Daniel , Whitaker Iain S. , Grinsell Damien , Ashton Mark W. , Acosta Rafael
Published: August 2010

Background:

While modern reconstructive surgery was revolutionized with the introduction of microsurgical techniques, microsurgery itself has seen the introduction of a range of technological aids and modern techniques aiming to improve dissection times, anastomotic times, and overall outcomes. These include improved preoperative planning, anastomotic aides, and earlier detection of complications with higher salvage rates. Despite the potential for substantial impact, many of these techniques have been evaluated in a limited fashion, and the evidence for each has not been universally explored. The purpose of this review was to establish and quantify the evidence for each technique.

Methods:

A search of relevant medical databases was performed to identify literature providing evidence for each technology. Levels of evidence were thus accumulated and applied to each technique.

Results:

There is a relative paucity of evidence for many of the more recent technologies described in the field of microsurgery, with no randomized controlled trials, and most studies in the field comprising case series only. Current evidence‐based suggestions include the use of computed tomographic angiography (CTA) for the preoperative planning of perforator flaps, the intraoperative use of a mechanical anastomotic coupling aide (particularly the Unilink® coupler), and postoperative flap monitoring with strict protocols using clinical bedside monitoring and/or the implantable Doppler probe.

Conclusion:

Despite the breadth of technologies introduced into the field of microsurgery, there is substantial variation in the degree of evidence presented for each, suggesting the role for much future research, particularly from emerging technologies such as robotics and modern simulators. © 2010 Wiley‐Liss, Inc. Microsurgery, 2010.
NMR quantification using an artificial signal
Authors: Farrant Roger D. , Hollerton John C. , Lynn Sean M. , Provera Stefano , Sidebottom Philip J. , Upton Richard J.
Published: August 2010

We have developed QUANTAS (QUANTification by Artificial Signal), which is a software‐based protocol for concentration measurement by NMR. QUANTAS is an absolute intensity external standard method for quantification by NMR that compensates for various experimental parameters. It is applicable to all nuclei and modern spectrometers. QUANTAS is demonstrated here for 1H and 19F NMR, enabling heteronuclear integrals to be compared. It can be applied using fixed probe tuning, matching and pulse length, for samples with the same effective loading on the probe coil as the appropriate reference spectrum. Otherwise, an optimised tuning and matching approach is adopted for every sample together with explicit PULCON (PUlse Length‐based CONcentration measurements) absolute intensity corrections. Copyright © 2010 John Wiley & Sons, Ltd.
Enhanced chromatographic NMR with polyethyleneglycol. A novel resolving agent for diffusion ordered spectroscopy
Authors: Kavakka Jari S. , Parviainen Viktor , Wähälä Kristiina , Kilpeläinen Ilkka , Heikkinen Sami
Published: August 2010

NMR analysis of complex mixtures can be significantly simplified using polyethyleneglycol (PEG) as resolving additive in DOSY NMR technique, which allows the extraction of individual spectra of mixture components with differing polarity. Resolving power of PEG‐assisted DOSY was demonstrated with natural product mixtures. Copyright © 2010 John Wiley & Sons, Ltd.
Sperm status and DNA dose play key roles in sperm/ICSI‐mediated gene transfer in caprine
Authors: Shadanloo Farshad , Najafi Mohammad Hasan , Hosseini Sayed Morteza , Hajian Mehdi , Forouzanfar Mohsen , Ghaedi Kamran , Abedi Parvaneh , Ostadhosseini Somaye , Hosseini Laleh , Eskandari‐Nasab Morad‐Pasha , Esfahani Mohammad Hossein Nasr
Published: August 2010

In relation to the growing recent interest in the establishment of sperm‐mediated gene transfer (SMGT) technology as a convenient and effective method for the simple production of transgenic animals, in this study the possibility of using SMGT to produce transgenic caprine embryos was investigated for the first time. Buck sperm were directly incubated with different concentrations (0–500 ng) of pcDNA/his/Lac‐Z plasmid and used for IVF or ICSI. Sperm used for ICSI were categorized into motile or live‐immotile group before being injected into oocytes. In a separate experiment, dead sperm prepared by repeated freezing/thawing were used for DNA‐incubation before ICSI. Sham injection was carried out by intracytoplasmic injection of approximately the same volume of media containing different doses of DNA using an ICSI needle. Transgene expression and transmission were detected by X‐Gal staining and PCR analysis of developed embryos, respectively. A reasonable blastocyst rate was observed in all the groups. Only embryos in the sham group were negative for transgene transmission. Transgene expression was completely dependent on the delivery technique and status of sperm, and was only observed in the live‐immotile and dead ICSI groups. The results of this study showed that the technique (IVF vs. ICSI vs. sham injection), sperm status (motile vs. live‐immotile vs. dead) and to some extent DNA concentration affect embryo development, transgene transmission and expression. Mol. Reprod. Dev. 77:868–875, 2010. © 2010 Wiley‐Liss, Inc.
Caffeine treatment of ovine cytoplasts regulates gene expression and foetal development of embryos produced by somatic cell nuclear transfer
Authors: Choi Inchul , Lee Joon‐Hee , Fisher Pat , Campbell Keith H.S.
Published: August 2010

Treatment of ovine oocytes during the latter stages of maturation in vitro with caffeine, a phosphodiesterase inhibitor, can increase the activities of maturation promoting factor and mitogen‐activated protein kinases at metaphase II. When used as cytoplast recipients for somatic cell nuclear transfer (NT), caffeine‐treated oocytes produced blastocysts with increased cell numbers. The objectives of these studies were to determine the effects of caffeine treatment on the expression profile of genes involved in early embryonic development and whether induction or maintenance of pregnancy was subsequently altered. No differences in overall expression patterns were observed between fertilised, caffeine‐treated fertilised and parthenogenetic embryos. In control NT embryos, altered levels of gene expression were found for OCT4, five genes regulated by OCT4 (H2AF.Z, NANOG, SOX2, FGF4 and INFT) and the heat‐shock response genes (HSP27 and HSP70.1). Levels of OCT4, H2AF.Z, NANOG, HSP 27 and FGF4 decreased, while those of INFT, HSP70.1 and SOX2 increased. In contrast, expression levels of these genes in caffeine‐treated NT embryos were similar to those in fertilised controls. Following transfer to surrogate recipients no differences were observed in the frequency of pregnancy; however, ewes receiving caffeine‐treated embryos maintained pregnancies for longer periods and delivered a live lamb. Taken together, these results suggest that treatment of ovine oocytes with caffeine can affect gene expression and improve developmental competence. Further studies on the mechanisms behind this alteration of gene expression are required and will aid in understanding the molecular mechanisms involved in nuclear reprogramming. Mol. Reprod. Dev. 77:876–887, 2010. © 2010 Wiley‐Liss, Inc.
MRI contrast from relaxation along a fictitious field (RAFF)
Authors: Liimatainen Timo , Sorce Dennis J. , O'Connell Robert , Garwood Michael , Michaeli Shalom
Published: August 2010

A new method to measure rotating frame relaxation and to create contrast for MRI is introduced. The technique exploits relaxation along a fictitious field (RAFF) generated by amplitude‐ and frequency‐modulated irradiation in a subadiabatic condition. Here, RAFF is demonstrated using a radiofrequency pulse based on sine and cosine amplitude and frequency modulations of equal amplitudes, which gives rise to a stationary fictitious magnetic field in a doubly rotating frame. According to dipolar relaxation theory, the RAFF relaxation time constant (TRAFF) was found to differ from laboratory frame relaxation times (T1 and T2) and rotating frame relaxation times (T1ρ and T2ρ). This prediction was supported by experimental results obtained from human brain in vivo and three different solutions. Results from relaxation mapping in human brain demonstrated the ability to create MRI contrast based on RAFF. The value of TRAFF was found to be insensitive to the initial orientation of the magnetization vector. In the RAFF method, the useful bandwidth did not decrease as the train length increased. Finally, as compared with an adiabatic pulse train of equal duration, RAFF required less radiofrequency power and therefore can be more readily used for rotating frame relaxation studies in humans. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Contrast‐enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood‐brain barrier with ultrasound
Authors: Howles Gabriel P. , Bing Kristin F. , Qi Yi , Rosenzweig Stephen J. , Nightingale Kathryn R. , Johnson G. Allan
Published: August 2010

The use of contrast agents for neuroimaging is limited by the blood‐brain barrier (BBB), which restricts entry into the brain. To administer imaging agents to the brain of rats, intracarotid infusions of hypertonic mannitol have been used to open the BBB. However, this technically challenging approach is invasive, opens only a limited region of the BBB, and is difficult to extend to mice. In this work, the BBB was opened in mice, using unfocused ultrasound combined with an injection of microbubbles. This technique has several notable features: it (a) can be performed transcranially in mice; (b) takes only 3 min and uses only commercially available components; (c) opens the BBB throughout the brain; (d) causes no observed histologic damage or changes in behavior (with peak‐negative acoustic pressures of 0.36 MPa); and (e) allows recovery of the BBB within 4 h. Using this technique, Gadopentetate Dimeglumine (Gd‐DTPA) was administered to the mouse brain parenchyma, thereby shortening T1 and enabling the acquisition of high‐resolution (52 × 52 × 100 micrometers3) images in 51 min in vivo. By enabling the administration of both existing anatomic contrast agents and the newer molecular/sensing contrast agents, this technique may be useful for the study of mouse models of neurologic function and pathology with MRI. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Noninvasive detection of pulmonary tissue destruction in a mouse model of emphysema using hyperpolarized 129Xe MRS under spontaneous respiration
Authors: Imai Hirohiko , Kimura Atsuomi , Iguchi Satoshi , Hori Yuki , Masuda Shoko , Fujiwara Hideaki
Published: August 2010

In the present study, a chemical shift saturation recovery method in hyperpolarized 129Xe MR spectroscopy measurements was applied to two groups of spontaneously breathing mice, an elastase‐induced emphysema model and a control group. Parameters detected were those related to lung structures and functions, such as alveolar septal thickness, h, the ratio of the alveolar septal volume relative to gas space volume, Vs/Va, and the transit time of blood through the gas exchange region, τ. To investigate the potential of these parameters as biomarkers, an attempt was made to detect physiologic changes in the lungs of elastase‐treated mice. Our results showed that Vs/Va was significantly reduced in elastase‐treated mice, reflecting emphysema‐like destruction of the alveolar wall. Compared with histologic results, this degree of reduction was shown to reflect the severity of wall destruction. On the other hand, significant changes in other parameters, h and τ, were not shown. This study is the first application of hyperpolarized 129Xe MR spectroscopy to a mouse model of emphysema and shows that the Vs/Va volume ratio is an effective biomarker for emphysema that could become useful in drug research and development through noninvasive detection of pathologic changes in small rodents. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Ongoing dual‐angle measurements for the correction of partial saturation in 31P MR spectroscopy
Authors: Tyler Damian J. , Lopez Orlando , Cole Mark A. , Carr Carolyn A. , Stuckey Daniel J. , Lakatta Edward , Clarke Kieran , Spencer Richard G.
Published: August 2010

Use of a repetition time similar to, or shorter than, metabolite T1s is common in NMR spectroscopy of biological samples to improve the signal‐to‐noise ratio. Conventionally, the partial saturation that results from this is corrected using saturation factors. However, this can lead to erroneous results in the presence of chemical exchange or nonconstant T1s. We describe an alternative approach to correction for saturation, based on ongoing dual‐angle T1 measurement. Using 31P magnetic resonance spectroscopy of the perfused rat heart undergoing ischemia‐reperfusion, we demonstrate that signal alternations in the data acquired by the dual‐angle approach are eliminated by the ongoing dual‐angle T1 measurement correction scheme, meaning that metabolite concentration and T1 measurement can be made throughout the course of the ischemia‐reperfusion protocol. Simulations, based on parameters pertinent to the perfused rat heart, demonstrate that accurate saturation correction is possible with this method except at times of rapid concentration change. Additionally, compared to the conventional saturation factor correction method, the ongoing dual‐angle T1 measurement correction scheme results in improved accuracy in determining the [phosphocreatine] recovery time constant. Thus, the ongoing dual‐angle T1 measurements procedure permits accurate monitoring of metabolite concentrations even in the setting of chemical exchange and T1 changes and allows more accurate analysis of bioenergetic status. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Human brain atlas‐based volumetry and relaxometry: Application to healthy development and natural aging
Authors: Hasan Khader M. , Walimuni Indika S. , Kramer Larry A. , Frye Richard E.
Published: August 2010

This work investigated the feasibility and utility of using T2‐weighted or dual spin‐echo data to provide volume and T2 relaxation time for regional and global gray and white matter using standardized brain templates and anatomically labeled atlases. A total of 130 healthy males and females (age range 15–59 years) were included. Dual echo magnetic resonance imaging data were acquired and analyzed using standardized International Consortium for Human Brain Mapping atlas‐based tissue segmentation procedures implemented in the statistical parametric mapping toolbox to obtain the age trajectories of volume and corresponding T2 relaxation time in whole brain white and gray matter, in the caudate nucleus and in the anterior limb of internal capsule. Whole brain gray matter and caudate nucleus volumes linearly decreased with age while whole brain white matter and anterior limb internal capsule volume increased slowly with age bilaterally in males and females. The relation between T2 relaxation time and age of whole brain gray and white matter, and caudate nucleus and anterior limb internal capsule followed a quadratic U‐curve. The T2 relaxation times of the human brain followed a U curve both globally and regionally in both white and gray matter. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Strain and torsion quantification in mouse hearts under dobutamine stimulation using 2D multiphase MR DENSE
Authors: Zhong Jia , Yu Xin
Published: August 2010

In this study, a 2D multiphase magnetic resonance displacement encoding with stimulated echoes (DENSE) imaging and analysis method was developed for direct quantification of Lagrangian strain in the mouse heart. Using the proposed method, <10 ms temporal resolution and 0.56 mm in‐plane resolution were achieved. A validation study that compared strain calculation by displacement encoding with stimulated echoes and by magnetic resonance tagging showed high correlation between the two methods (R2 > 0.80). Regional ventricular wall strain and twist were characterized in mouse hearts at baseline and under dobutamine stimulation. Dobutamine stimulation induced significant increase in radial and circumferential strains and torsion at peak systole. A rapid untwisting was also observed during early diastole. This work demonstrates the capability of characterizing cardiac functional response to dobutamine stimulation in the mouse heart using 2D multiphase magnetic resonance displacement encoding with stimulated echoes. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Performance of external and internal coil configurations for prostate investigations at 7 T
Authors: Metzger Gregory J. , van de Moortele Pierre‐Francois , Akgun Can , Snyder Carl J. , Moeller Steen , Strupp John , Andersen Peter , Shrivastava Devashish , Vaughan Tommy , Ugurbil Kamil , Adriany Gregor
Published: August 2010

Three different coil configurations were evaluated through simulation and experimentally to determine safe operating limits and evaluate subject size‐dependent performance for prostate imaging at 7 T. The coils included a transceiver endorectal coil (trERC), a 16‐channel transceiver external surface array (trESA) and a trESA combined with a receive‐only ERC (trESA+roERC). Although the transmit B1 (B) homogeneity was far superior for the trESA, the maximum achievable B is subject size dependent and limited by transmit chain losses and amplifier performance. For the trERC, limitations in transmit homogeneity greatly compromised image quality and limited coverage of the prostate. Despite these challenges, the high peak B close to the trERC and subject size‐independent performance provides potential advantages especially for spectroscopic localization where high‐bandwidth radiofrequency pulses are required. On the receive side, the combined trESA+roERC provided the highest signal‐to‐noise ratio and improved homogeneity over the trERC resulting in better visualization of the prostate and surrounding anatomy. In addition, the parallel imaging performance of the trESA+roERC holds strong promise for diffusion‐weighted imaging and dynamic contrast‐enhanced MRI. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Reference‐based linear curve fitting for bolus arrival time estimation in 4D MRA and MR perfusion‐weighted image sequences
Authors: Forkert Nils Daniel , Fiehler Jens , Ries Thorsten , Illies Till , Möller Dietmar , Handels Heinz , Säring Dennis
Published: August 2010

The bolus arrival time (BAT) based on an indicator dilution curve is an important hemodynamic parameter. As the direct estimation of this parameter is generally problematic, various parametric models have been proposed that describe typical physiological shapes of indicator dilution curves, but it remains unclear which model describes the real physiological background. This article presents a method that indirectly incorporates physiological information derived from the data available. For this, a patient‐specific hemodynamic reference curve is extracted, and the corresponding reference BAT is determined. To estimate a BAT for a given signal curve, the reference curve is fitted linearly to the signal curve. The parameters of the fitting process are then used to transfer the reference BAT to the signal curve. The validation of the method proposed based on Monte Carlo simulations showed that the approach presented is capable of improving the BAT estimation precision compared with standard BAT estimation methods by up to 59% while at the same time reduces the computation time. A major benefit of the method proposed is that no assumption about the underlying distribution of indicator dilution has to be made, as it is implicitly modeled in the reference curve. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Protein polymer MRI contrast agents: Longitudinal analysis of biomaterials in vivo
Authors: Karfeld‐Sulzer Lindsay S. , Waters Emily A. , Kohlmeir Ellen K. , Kissler Hermann , Zhang Xiaomin , Kaufman Dixon B. , Barron Annelise E. , Meade Thomas J.
Published: August 2010

Despite recent advances in tissue engineering to regenerate biological function by combining cells with material supports, development is hindered by inadequate techniques for characterizing biomaterials in vivo. Magnetic resonance imaging is a tomographic technique with high temporal and spatial resolution and represents an excellent imaging modality for longitudinal noninvasive assessment of biomaterials in vivo. To distinguish biomaterials from surrounding tissues for magnetic resonance imaging, protein polymer contrast agents were developed and incorporated into hydrogels. In vitro and in vivo images of protein polymer hydrogels, with and without covalently incorporated protein polymer contrast agents, were acquired by magnetic resonance imaging. T1 values of the labeled gels were consistently lower when protein polymer contrast agents were included. As a result, the protein polymer contrast agent hydrogels facilitated fate tracking, quantification of degradation, and detection of immune response in vivo. For the duration of the in vivo study, the protein polymer contrast agent‐containing hydrogels could be distinguished from adjacent tissues and from the foreign body response surrounding the gels. The hydrogels containing protein polymer contrast agent have a contrast‐to‐noise ratio 2‐fold greater than hydrogels without protein polymer contrast agent. In the absence of the protein polymer contrast agent, hydrogels cannot be distinguished by the end of the gel lifetime. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Highly localized positive contrast of small paramagnetic objects using 3D center‐out radial sampling with off‐resonance reception
Authors: Seevinck Peter R. , de Leeuw Hendrik , Bos Clemens , Bakker Chris J. G.
Published: August 2010

In this article, we present a 3D imaging technique, applying center‐out RAdial Sampling with Off‐Resonance reception, to accurately depict and localize small paramagnetic objects with high positive contrast while suppressing long T2* components. The center‐out RAdial Sampling with Off‐Resonance reception imaging technique is a fully frequency‐encoded 3D ultrashort echo time acquisition method, which uses a large excitation bandwidth and off‐resonance reception. By manually introducing an offset, Δf0, to the central reception frequency (f0), the typical radial signal pileup observed in 3D center‐out sampling caused by a dipolar magnetic field disturbance can be shifted toward the source of the field disturbance, resulting in a hyperintense signal at the magnetic center of the small paramagnetic object. This was demonstrated both theoretically and using 1D time domain simulations. Experimental verification was done in a gel phantom and in inhomogeneous porcine tissue containing various objects with very different geometry and susceptibility, namely, subvoxel stainless steel spheres, a puncture needle, and paramagnetic brachytherapy seeds. In all cases, center‐out RAdial Sampling with Off‐Resonance reception was shown to generate high positive contrast exactly at the location of the paramagnetic object, as was confirmed by X‐ray computed tomography. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.