bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Approach to Accurate Diagnosis of Acute Appendicitis
Authors: Tzanakis Nikolaos E. , Efstathiou Stamatis P. , Danulidis Kecaris , Rallis Georgios E. , Tsioulos Dimitrios I. , Chatzivasiliou Anthimos , Peros Georgios , Nikiteas Nikolaos I. 
Published: August 2005

AbstractThis study aimed (1) to develop a simple scoring system incorporating ultrasound (US) examination and clinical or laboratory predictors for increasing diagnostic accuracy in acute appendicitis (AA), and (2) to evaluate the performance of the scoring system as compared to that of previous models. Fifteen variables including US assessment for patients admitted with suspected AA were considered in multivariate analysis using the finding of AA at operation as the end point (internal study). The new score, together with 11 previous ones, was applied to a prospective independent population of subjects with suspected AA, and the respective performances were compared (external validation study). Among 303 patients (170 males, mean age 28.3 ± 13.3 years) of the internal study, 161 went on to surgery, and 130 had AA at operation. Four independent correlates of AA were identified and used for the derivation of the following integer‐based scoring system: number of points = 6 for US demonstrating AA + 4 for tenderness in the right lower quadrant + 3 for rebound tenderness + 2 for leukocyte count >12,000/μl. In the external study (201 subjects, 105 males, mean age 28.7 ± 11.9 years, 109 operated, 87 with AA), when the cut‐off of ≥ 8 points for AA was used, sensitivity, specificity, accuracy, and area under the curve of the proposed score were 95.4%, 97.4%, 96.5%, and 93%, respectively, exceeding noticeably the previous models. The proposed scoring system introduces a quantitative combination of the clinical evaluation with US imaging and a marker of inflammatory response, which may enhance the diagnostic accuracy for subjects with suspected AA especially in geographical areas where CT scanning is not readily available on a 24‐hour basis.
The Delay in Diagnosis of Slipped Capital Femoral Epiphysis: A Review of 102 Patients
Authors: Green Daniel W. , Reynolds Richard A. K. , Khan Safdar N. , Tolo Vernon 
Published: August 2005

Objectives The aim of this study were (1) to evaluate the incidence of apparent missed diagnosis of slipped capital femoral epiphysis (SCFE) by the primary care system and (2) to identify possible factors leading to a delay in diagnosis of this disorder. Setting and Design A retrospective review of emergency department records, outside medical charts, and preoperative and postoperative radiographs of children treated surgically for SCFE at the Children's Hospital of Los Angeles (CHLA) from 1989 to 1997 was done to assess the delay in diagnosis for SCFE. The primary care system included outside emergency department visits, urgent care clinic visits, and private office visits. Results Of 102 patients (69 men, 33 women; mean age at surgery, 11.9 years), 68% were above the 95th percentile mean weight for age. Pain in the hip and/or groin was documented in 60%. The mean duration of symptoms experienced before being seen at CHLA was 140 days (hours to 1.5 years) and the mean delay after the first primary care visit till being seen at CHLA was 76 days (hours to 1 year). Fifty-two percent of primary care visits for hip, groin, knee, or thigh pain in obese children did not lead to either a diagnosis of SCFE or a referral for orthopedic evaluation. Conclusions This study documents a 2 1/2-month delay and a 52% incidence of apparent missed diagnosis for SCFE by the primary care system. There seems to be a need for increased orthopedic education for primary care providers.
Mechanisms of xenon‐ and isoflurane‐induced preconditioning – a potential link to the cytoskeleton via the MAPKAPK‐2/HSP27 pathway
Authors: Weber Nina C , Toma Octavian , Wolter Jessica I , Wirthle Nicole M , Schlack Wolfgang , Preckel Benedikt 
Published: August 2005

We previously demonstrated that the anesthetic gas xenon exerts cardioprotection by preconditioning in vivo via activation of protein kinase C (PKC)‐ɛ and p38 mitogen‐activated protein kinase (MAPK). P38 MAPK interacts with the actin cytoskeleton via the MAPK‐activated protein kinase‐2 (MAPKAPK‐2) and heat‐shock protein 27 (HSP27). The present study further elucidated the underlying molecular mechanism of xenon‐induced preconditioning (Xe‐PC) by focusing on a potential link of xenon to the cytoskeleton.
Anesthetized rats received either xenon (Xe‐PC, n=6) or the volatile anesthetic isoflurane (Iso‐PC, n=6) during three 5‐min periods interspersed with two 5‐min and one final 10‐min washout period. Control rats (n=6) remained untreated for 45 min. Additional rats were either pretreated with the PKC inhibitor Calphostin C (0.1 mg kg−1) or with the p38 MAPK inhibitor SB203580 (1 mg kg−1) with and without anesthetic preconditioning (each, n=6). Hearts were excised for immunohistochemistry of F‐actin fibers and phosphorylated HSP27. Phosphorylation of MAPKAPK‐2 and HSP27 were assessed by Western blot. HSP27 and actin colocalization were investigated by co‐immunoprecipitation.
Xe‐PC induced phosphorylation of MAPKAPK‐2 (control 1.0±0.2 vs Xe‐PC 1.6±0.1, P<0.05) and HSP27 (control 5.0±0.5 vs Xe‐PC 9.8±1.0, P<0.001). Both effects were blocked by Calphostin C and SB203580. Xe‐PC enhanced translocation of HSP27 to the particulate fraction and increased F‐actin polymerization. F‐actin and pHSP27 were colocalized after Xe‐PC.
Xe‐PC activates MAPKAPK‐2 and HSP27 downstream of PKC and p38 MAPK. These data link Xe‐PC to the cytoskeleton, revealing new insights into the mechanisms of Xe‐PC in vivo.

British Journal of Pharmacology (2005) 146, 445–455. doi:10.1038/sj.bjp.0706324
Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating adenosine A1 receptor in a manner different from its classical agonists
Authors: Liu Da‐Zhi , Xie Ke‐Qiang , Ji Xin‐Quan , Ye Yang , Jiang Cheng‐Liang , Zhu Xing‐Zu 
Published: August 2005

The effects of paeoniflorin (PF), a compound isolated from Paeony radix, on neurological impairment and histologically measured infarction volume following transient and permanent focal ischemia were examined in Sprague–Dawley rats.
In transient ischemia model, rats were subjected to a 1.5‐h occlusion of the middle cerebral artery (MCA). The administration of PF (2.5 and 5 mg kg−1, s.c.) produced a dose‐dependent decrease in both neurological impairment and the histologically measured infarction volume. Similar results were also obtained when PF (2.5, 5, and 10 mg kg−1, s.c.) was given in permanent ischemia model.
The neuroprotective effect of PF (10 mg kg−1, s.c.) was abolished by pretreatment of DPCPX (0.25 mg kg−1, s.c.), a selective adenosine A1 receptor (A1R) antagonist.
PF (10, 40, and 160 mg kg−1, i.v.) had no effect on mean arterial pressure (MAP) and heart rates (HR) in the conscious rat. Additionally, PF (10−3 mol l−1) had no effect on noradrenaline‐ (NA‐) or high K+ concentration‐induced contractions of isolated rabbit primary artery.
In competitive binding experiments, PF did not compete with the binding of [3H]DPCPX, but displaced the binding of [3H]NECA to the membrane preparation of rat cerebral cortex. This binding manner was distinguished from the classical A1R agonists.
The results demonstrated that activation of A1R might be involved in PF‐induced neuroprotection in cerebral ischemia in rat. However, PF had no ‘well‐known’ cardiovascular side effects of classical A1R agonists. The results suggest that PF might have the potential therapeutic value as an anti‐stroke drug.

British Journal of Pharmacology (2005) 146, 604–611. doi:10.1038/sj.bjp.0706335
Intracellular pathways triggered by the selective FLT‐1‐agonist placental growth factor in vascular smooth muscle cells exposed to hypoxia
Authors: Bellik Lydia , Vinci Maria Cristina , Filippi Sandra , Ledda Fabrizio , Parenti Astrid 
Published: August 2005

We have previously shown that hypoxia makes vascular smooth muscle cells (VSMCs) responsive to placental growth factor (P1GF) through the induction of functional fms‐like tyrosine kinase (Flt‐1) receptors. The aim of this study was to investigate the molecular mechanisms involved in the P1GF effects on proliferation and contraction of VSMCs previously exposed to hypoxia (3% O2).
In cultured rat VSMCs exposed to hypoxia, P1GF increased the phosphorylation of protein kinase B (Akt), p38 and STAT3; activation of STAT3 was higher than that of other kinases. In agreement with this finding, the proliferation of hypoxia‐treated VSMCs in response to P1GF was significantly impaired by the p38 and the phosphatidylinositol 3‐kinase inhibitors SB202190 and LY294002, respectively, and was almost completely prevented by AG490, a janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) inhibitor.
Since hypoxia was able to reverse the vasorelaxant effect of P1GF into a vasoconstrictor response, the mechanism of this latter effect was also investigated. Significant Flt‐1 activity was measured in isolated preparations from rat aorta exposed to hypoxia. Inhibitors of mitogen‐activated protein kinase kinase, Akt and STAT3 induced a modest inhibition of the vasoconstrictor response to P1GF, while the p38 inhibitor SB202190 markedly impaired the P1GF‐induced contractile response. These effects were selectively mediated by Flt‐1 without any involvement of foetal liver kinase‐1 receptors.
These data are the first evidence that different intracellular pathways activated by Flt‐1 receptor in VSMCs are involved in diverse biological effects of P1GF: while mitogen activated protein kinase kinase/extracellular signal regulated kinase1/2 and JAK/STAT play a role in VSMC proliferation, p38 is involved in VSMC contraction. These findings may highlight the role of P1GF in vascular pathology.

British Journal of Pharmacology (2005) 146, 568–575. doi:10.1038/sj.bjp.0706347
Abolition of chondral mineralization by group III metabotropic glutamate receptors expressed in rodent cartilage
Authors: Wang Liyang , Hinoi Eiichi , Takemori Akihiro , Takarada Takeshi , Yoneda Yukio 
Published: August 2005

Previous studies have demonstrated the functional expression by osteoblasts of glutamate (Glu) signaling machineries responsible for the stimulation of cell proliferation and differentiation in bone, while there is no information available on the expression of the Glu signaling system by cartilage to date.
In cultured mouse embryonic metatarsals isolated before vascularization, chondral mineralization was almost completely inhibited in the presence of the group III metabotropic Glu receptor (mGluR) agonist L‐(1)‐2‐amino‐4‐phosphonobutyrate (L‐AP4) in a manner sensitive to an antagonist, with the total length being unchanged.
A group II mGluR agonist was similarly more effective in inhibiting the mineralization than a group I mGluR agonist, while none of ionotropic GluR agonists drastically affected the mineralization.
Both histological and in situ hybridization analyses revealed that L‐AP4 specifically inhibited chondral mineralization, without apoptotic cell death, in cultured metatarsals.
In addition to the constitutive expression of mRNA for particular mGluRs in both cultured mouse metatarsals and rat costal chondrocytes, L‐AP4 significantly inhibited the accumulation of cyclic AMP by forskolin and parathyroid hormone in a manner sensitive to a group III mGluR antagonist in cultured chondrocytes.
Moreover, L‐AP4 drastically inhibited the expression of osteopontin mRNA in both cultured metatarsals and chondrocytes.
These results suggest that Glu may at least in part play a role as a signal mediator in mechanisms associated with chondral mineralization through the group III mGluR subtype functionally expressed by chondrocytes in rodent cartilage.

British Journal of Pharmacology (2005) 146, 732–743. doi:10.1038/sj.bjp.0706358
Caspase Inhibition Enhances Ischemic Tolerance of Fasciocutaneous Flaps
Authors: Sumer Baran D. , Gastman Brian R. , Gao Feng , Haughey Bruce H. , Paniello Randal C. , Nussenbaum Brian 
Published: August 2005

AbstractObjectives/Hypothesis: To demonstrate the significance of apoptosis in ischemia‐reperfusion injury in revascularized fasciocutaneous flaps and test the hypothesis that pharmacologic inhibition of caspases prolongs the allowable primary ischemia time of these flaps.Study Design: Animal study using the epigastric flap in adult male Sprague‐Dawley rats.Methods: Fifty‐nine rats were treated with the caspase inhibitor (Q‐VD‐OPH) reconstituted in dimethylsulfoxide (DMSO) (n = 20, 8 mg/kg:0.8 mL/kg), DMSO alone (n = 19, 0.8 mL/kg), or saline (n = 20, 0.8 mL/kg). Treatment was given as a single intraperitoneal injection 30 minutes before starting primary ischemia. Epigastric flaps were subjected to increasing ischemia times followed by reperfusion. The flaps were harvested and analyzed 7 days later, and viability was assessed. Probit statistical analysis was used to determine the critical ischemia time. This was defined as the time point when 50% of the flaps in each group were expected to survive.Results: The calculated critical ischemia times were 8.92 hours (95% confidence interval 7.19–10.47 h) for the saline group, 16.35 hours (95% confidence interval 11.82–19.89 h) for the DMSO group, and 21.73 hours (95% confidence interval 19.39–25.37 h) for the DMSO with Q‐VD‐OPH group. These differences were significantly different from each other.Conclusions: Pretreatment of fasciocutaneous flaps with a free radical scavenger alone or in combination with a caspase inhibitor significantly increases the flap's tolerance of primary ischemia. The added benefit of the caspase inhibitor suggests that apoptosis plays an important role in ischemia‐reperfusion injury in soft tissue flaps.
Perioperative Parathyroid Hormone Assay for Diagnosis and Management of Postthyroidectomy Hypocalcemia
Authors: Scurry W Cooper , Beus Kirt S. , Hollenbeak Christopher S. , Stack Brendan C. 
Published: August 2005

AbstractObjectives/Hypothesis: The purpose of this study was to assess the relationship between perioperative changes in parathyroid hormone (PTH) level and the likelihood of postthyroidectomy hypocalcemia.Study Design: In a series of 78 patients undergoing total or completion thyroidectomy, PTH levels were measured before surgery and at 10 minutes after removal of the thyroid gland.Methods: A prospective, nonrandomized collection of serum from 78 consecutive total or completion thyroidectomy procedures performed by a single surgeon was carried out over 18 months. Analysis is made of PTH levels, serum calcium values, need for calcium supplementation, and symptoms of hypocalcemia.Results: Both a PTH change of 75% and an absolute postoperative PTH of 7 pg/mL are accurate standards for predicting symptomatic hypocalcemia after total or completion thyroid surgery.Conclusions: Perioperative PTH levels are a tool for the prediction of postoperative symptomatic hypocalcemia after thyroidectomy. A PTH level drawn 10 minutes after removal of the thyroid predicts the likelihood of postoperative hypocalcemia.
Intranasal Lysine‐Aspirin in Aspirin‐Sensitive Nasal Polyposis: A Controlled Trial
Authors: Parikh Abhi A. , Scadding Glenis K. 
Published: August 2005

AbstractObjectives/Hypothesis: Intranasal lysine‐aspirin has been used as a method of desensitization in patients with aspirin‐sensitive nasal polyps to control their recurrence and prevent frequent surgical intervention. However, the studies are limited in number, and their design is open to criticisms. Thus, we conducted a controlled trial to study the clinical effectiveness of topical lysine‐aspirin in patients with aspirin‐sensitive nasal polyposis.Study Design: Prospective, randomized, double blind, placebo controlled, crossover trial.Methods: Aspirin‐sensitive patients confirmed by intranasal challenge were enrolled and randomized to receive 16 mg of topical lysine‐aspirin every 48 hours or placebo for 6 months before crossover. Polyp growth and nasal and chest symptoms were monitored using acoustic rhinometry, nasal inspiratory peak flow, peak expiratory flow rate, and a daily diary of symptom scores.Results: Twenty‐two patients were enrolled. After withdrawals and drop outs, data were available on 11 patients for analysis. Multivariate analysis of measured parameters did not reveal a significant clinical benefit to patients receiving topical lysine‐aspirin compared with placebo. Deterioration was similar while on lysine‐aspirin or placebo.Conclusions: This is the first controlled clinical trial of topical desensitization in aspirin‐sensitive nasal polyp patients. Despite the failure to demonstrate clinical benefit, tissue studies have shown a significant improvement at the microscopic level.1 Further work with larger numbers of patients along with conventional treatment may show a clinical improvement in these patients.
Differential Penetration of Ototopicals and Water through Tympanostomy Tubes
Authors: Smith Lee P. , Smullen Jennifer L. , Younis Ramzi T. 
Published: August 2005

AbstractObjective: To evaluate the penetration of ototopicals and water through tympanostomy tubes (TT) using a physical model.Study Design: An in vitro model was created to measure the ability of various solutions to penetrate a variety of TT.Methods: A TT was placed through a perforation (myringotomy) in a silastic sheet (tympanic membrane) fixed between the ends of two 1 mL syringes. Measurements were obtained of the maximum height various liquids (tap water, 2% soapy water, ocean water, ofloxacin otic, corticosporin otic, and ciprofloxacin/dexamethasone otic) achieved before penetrating different TTs (1.0 mm or 1.27 mm Paparella silicone, 1.14 mm or 1.27 mm Reuter Bobbin titanium, 1.27 mm Collar Button fluoroplastic or 1.14 mm T‐type silicone).Results: Two percent soapy water was significantly more permeable than water and ocean water in all tubes studied. Ciprofloxacin/dexamethasone otic was significantly more permeable than tap water, ocean water, and ofloxacin otic in only the Collar Button fluoroplastic TT. Our results suggest that titanium TTs are more permeable than other TT. Otherwise, ototopicals, tap water, and ocean water behaved similarly across all TT studied.Conclusions: Our results demonstrate that ototopicals, tap water, and ocean water behave similarly with regard to TT penetration. Ciprofloxacin/dexamethasone otic may have better penetration than other ototopicals. Titanium TT may be easier to penetrate than other TT.
Factors Affecting Cancer Recurrence after Microvascular Flap Reconstruction of the Head and Neck
Authors: Roostaeian Jason , Suh Jeffrey D. , Sercarz Joel A. , Abemayor Elliot , Lee Jivianne T. , Blackwell Keith E. 
Published: August 2005

AbstractObjective: Our objective was to determine which factors are associated with cancer recurrence after microvascular reconstruction of the head and neck for squamous cell carcinoma (SCC).Study Design: A cohort of patients who fit the inclusion/exclusion criteria were identified retrospectively.Methods: A group of 184 patients who underwent successful surgical resection and simultaneous microvascular reconstruction of the head and neck for treatment of SCC were identified. The mean age was 60 (range 23–90) years, there were 115 males and 69 females, and mean follow‐up was 26.2 (range 1–99) months. Various factors were analyzed to determine whether they were associated with cancer recurrence, including those pertaining to 1) recipient vessel choice, 2) prior cancer treatment, and 3) cancer staging criteria. Statistical analysis was performed using SPSS statistical software.Results: Overall cancer stage (P = .005), T stage (P = .0001), history of previous cancer treatment (P = .004), and history of previous chemotherapy (P = .044) were found to be statistically significant predictors of cancer recurrence on univariate analysis. However, on multivariate analysis, only T stage (P = .005) and history of previous cancer treatment (P = .008) remained as statistically significant predictors of cancer recurrence. Recipient vessel selection was not statistically associated with cancer recurrence.Conclusions: In our study, only T stage and a history of previous cancer treatment were associated with increased cancer recurrence. Neither the recipient vessel chosen nor its location impacted cancer recurrence. This suggests that recipient vessel selection and preparation for microvascular reconstruction do not jeopardize the adequacy of oncologic resection and are therefore oncologically sound.
Methylation‐Associated Silencing of Death‐Associated Protein Kinase Gene in Laryngeal Squamous Cell Cancer
Authors: Kong Wei‐Jia , Zhang Song , Guo Changkai , Zhang Sulin , Wang Yanjun , Zhang Dan 
Published: August 2005

AbstractObjectives/Hypothesis: Death‐associated protein kinase (DAPK) is a Ca2+/calmodulin‐regulated Ser/Thr kinase that functions as a positive mediator of programmed cell death. It has been found that DAPK gene is frequently inactivated by its promoter hypermethylation in some cancers and tumor cell lines. However, it is not clear whether promoter hypermethylation of DAPK gene exists in laryngeal squamous cell cancer (LSCC). The aim of this study was to investigate the promoter methylation status of the DAPK gene in LSCC and the effect of 5‐Aza‐2'‐deoxycytidine (5‐Aza‐CdR), a demethylating agent, on Hep‐2 cells, a human laryngeal cancer cell line, and on xenografts of Hep‐2.Methods: Methylation‐specific polymerase chain reaction (PCR) and reverse‐transcription PCR techniques were used to determine the promoter methylation status and mRNA expression of DAPK gene in LSCC. Furthermore, Hep‐2 cells in vitro and in vivo were treated by 5‐Aza‐CdR to explore the effect of demethylating agents on DAPK mRNA expression and tumor growth.Results: Hypermethylation of DAPK gene promoter was found in 39 (67.2%) of 58 LSCC samples. There was no significant difference in the promoter hypermethylation rate among the samples of different histologic grades or samples from patients with different T stages. However, there was significant difference in methylation status of DAPK gene between the samples from patients in N0 stages and those from patients in N1 stages. No promoter hypermethylation of DAPK gene was found in any of the five normal laryngeal tissue samples. DAPK mRNA expression was not detected in tumor specimens with promoter hypermethylation. On the contrary, DAPK mRNA expression was observed in the unmethylated tumor specimens, specimens from tissues adjacent to the tumor, and normal laryngeal tissues samples. Promoter hypermethylation of DAPK gene was found, and no DAPK mRNA expression was detected in Hep‐2 cells. DAPK mRNA expression in Hep‐2 cells and xenografts could be restored by treating cells and xenografts with 5‐Aza‐CdR. The tumors' xenografts, induced by way of Hep‐2 cell injection in nude mice treated with 5‐Aza‐CdR, were obviously smaller than those in nude mice treated with phosphate‐buffered saline.Conclusions: Abnormal loss of DAPK expression could be associated with aberrant promoter region methylation in the LSCC. 5‐Aza‐CdR may slow the growth of Hep‐2 cells in vitro and in vivo by reactivating tumor suppressor gene DAPK silenced by de novo methylation.