bluuebunny/crossref_metadata_2025 huggingface dataset:
Prior Intraperitoneal Injection of Rat Recombinant IL-6 Increases Hypothalamic IL-6 Contents in Subsequent Forced Swim Stressor in Rats
Authors: Matsumoto Takuya , Komori Teruhisa , Yamamoto Masato , Shimada Yasuhito , Nakagawa Masanori , Shiroyama Takashi , Inui Koji , Okazaki Yuji
Published: February 2007

Background: Cytokines do not only mediate responses to infection, but are also involved in behavioral and physiological responses to psychological stressors. IL-6 has received special attention in relation to the development of posttraumatic stress disorders and depression. Objective: We tested effects of prior injection of rat recombinant IL-6 (rrIL-6) on behaviors induced by the forced swim (FS) stressor, and central and peripheral responses of IL-6 to FS. Methods: Rats were injected intraperitoneally with either rrIL-6 (250 ng/0.5 ml) or equal-volume sterile saline twice within an interval of 24 h. One hour after each injection, the rats were exposed to FS or remained at the home cage (control). Results: Injection of rrIL-6 did not affect immobility, swimming or climbing behaviors during FS compared with the saline control. Although FS was not a significant factor for hypothalamic and midbrain IL-6 mRNA and plasma IL-6 responses, FS with prior administration of rrIL-6 significantly increased hypothalamic IL-6 contents in response to FS compared with the saline injection-FS condition. Conclusions: Our results suggested that stressor alone had no influence on plasma IL-6 levels and IL-6 mRNA expression levels in midbrain and hypothalamus, but administration of rrIL-6 followed by FS significantly increased hypothalamic IL-6. Our results support the notion that the interaction between IL-6 and stressor might have implications for the pathophysiology of IL-6-induced depressive symptoms.
Changes in Autobiographical Memory Specificity following Cognitive Behavior Therapy and Pharmacotherapy for Major Depression
Authors: McBride Carolina , Segal Zindel , Kennedy Sidney , Gemar Michael
Published: February 2007

Background: An important cognitive marker of clinical depression is a reduced ability to be specific in recalling personal memories, a phenomenon coined ‘overgeneral memory’. Overgeneral memory is considered as a stable cognitive trait that is intrinsically linked with depression and independent of mood state. Previous studies show that autobiographical memory is modifiable. Sampling and Methods: This study investigated whether autobiographical memory is differentially affected by treatment type. Depressed patients were randomly assigned to receive either cognitive behavior therapy (CBT) for depression or pharmacotherapy (PHT). Results: The proportion of categoric memories decreased and the proportion of specific memories increased following both types of treatments, adding support to the view that overgeneral memory is modifiable. CBT also had a greater impact on reducing extended overgeneral memories compared to PHT. Conclusions: The results from the current study are important in that they show that overgeneral memory can be targeted and modified through brief treatment. The clinical significance of the finding that there was a greater decrease in extended memories in the CBT group is unclear.
Psychiatric Disorders in the Parents of Individuals with Infantile Autism: A Case-Control Study
Authors: Mouridsen Svend Erik , Rich Bente , Isager Torben , Nedergaard Niels Jørgen
Published: February 2007

Background: The rates and types of psychiatric disorders were studied in the parents of individuals with infantile autism (IA). Sampling and Methods: To estimate the prevalence and types of psychiatric disorders, the parents of 115 individuals with IA and the parents of 330 controls from the general population were screened through the nationwide Danish Psychiatric Central Register covering a period of 33 years. The IA individuals had been seen as in-patients at two university clinics of child psychiatry during a 25-year period and had been referred from the entire country of Denmark. Results: Psychiatric disorders were found in 15.7% of mothers with autistic children, which was significantly higher than the 8.2% found in the control group. The only diagnostic category in which a statistically significant overrepresentation could be found was that of personality disorder. A personality disorder diagnosis was found in 7.8% of mothers with autistic children in comparison to 2.1% of mothers in the control group. Conclusion: The findings so far suggest that in future studies it is important to pay attention to issues such as relatives examined, control groups and methods of data collection.
Hodgkin Lymphoma Accompanied by Aplastic Anemia and Polyclonal Expansion of Large Granular Lymphocytes
Authors: Saitoh Takayuki , Matsushima Takafumi , Yamane Arito , Sakuraya Masataka , Irisawa Hiroyuki , Yokohama Akihiko , Handa Hiroshi , Tsukamoto Norifumi , Karasawa Masamitsu , Nojima Yoshihisa , Murakami Hirokazu
Published: February 2007

Immunologic abnormalities have been described in patients with Hodgkin lymphoma, including autoimmune hemolytic anemia and immune thrombocytopenic purpura. The concurrent diagnoses of Hodgkin lymphoma and acquired aplastic anemia, however, is extremely rare. We report a 56-year-old Japanese female patient with severe aplastic anemia and increased large granular lymphocytes prior to the recurrence of Hodgkin lymphoma. After being in remission for 10 years from Hodgkin lymphoma, she developed progressive pancytopenia. The large granular lymphocytes (expressed CD3+ CD8+ TCRαβ+) had a polyclonal distribution, the serum-soluble FasL concentration was significantly elevated, and bone marrow biopsy showed severely hypocellular bone marrow without infiltration of abnormal lymphocytes. No lymphadenopathy was observed that would suggest a relapse of Hodgkin lymphoma. A diagnosis of aplastic anemia was made, and treatment with corticosteroids and cyclosporine was initiated. Two months later, she suddenly developed celiac and mediastinal lymphadenopathy. She underwent one cycle of chemotherapy before she died of progressive pancytopenia. Autopsy revealed the recurrence of Hodgkin lymphoma, nodular sclerosis in the lymph nodes and markedly hypocellular bone marrow. Although autoimmune disorders are described in Hodgkin lymphoma, our case shows a rare instance of a patient who had aplastic anemia as the first manifestation of a relapse of Hodgkin lymphoma.
Challenging Oral Contraception after Weight Loss by Bariatric Surgery
Authors: Merhi Zaher O.
Published: February 2007

As surgical weight loss becomes more commonly performed in fertile women, adequate contraception is more frequently becoming an issue. The purpose of this article is to appraise the literature to ascertain whether the use of oral contraception is effective and adequate after bariatric surgery. The literature search revealed that the combination of lower oral contraception dosages and surgical gastrointestinal disturbances might place patients at higher risks of unintended pregnancy. Until clinical trials show its efficacy, physicians should use oral contraception with prudence after bariatric surgery.
Effect of Melatonin on Healing of Colonic Anastomosis in a Rat Model of Peritonitis
Authors: Özen İ.O. , Ekingen G. , Taşlıpınar M.Y. , Bukan N. , Demiroğulları B. , Karabulut R. , Sönmez K. , Başaklar A.C. , Kale N.
Published: February 2007

Background: The aim of this study is to determine the effect of melatonin on intestinal anastomosis in the presence of peritonitis. Material and Methods: 32 Wistar albino rats were randomized into four groups (n = 8): A (sham), B (control), C (melatonin 5 mg/kg), and D (melatonin 10 mg/kg). In group A, only cecal dissection was carried out. In the other groups, cecal ligation and puncture (CLP) followed cecal dissection in order to induce bacterial peritonitis. 24 h after the previous operation, cecal resection and iliocolic anastomosis were performed in the rats of all groups. In group C (5 mg/kg) and group D (10 mg/kg), melatonin was injected for 5 consecutive days starting after CLP. At the 48th hour of the CLP procedure, blood was drawn via the tail vein for tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) analysis, and on the 4th day of the experiment relaparotomy was carried out for bursting pressure (BP) measurements. The intestinal tissue containing the anastomotic line was then snap-frozen in liquid nitrogen and stored at –80°C for determination of tissue levels of malondialdehyde (MDA) and glutathione (GSH). Results: The tissue MDA level, blood TNF-α and IL-6 levels of group B were significantly higher than in the other groups, whereas the BP results and GSH levels of group B were found to be significantly lower than in the other groups. The results of groups C and D are statistically different from those of group B. When we compared the results of groups C and D, we found significantly higher results in terms of BP and GSH levels in group D and also significantly lower results in terms of MDA, blood TNF-α and IL-6 levels in group D. Conclusion: The findings of this experiment suggest that melatonin has a dose-independent positive effect on wound healing of colonic anastomosis.
Automatic Pressure Titration with APAP Is as Effective as Manual Titration with CPAP in Patients with Obstructive Sleep Apnea
Authors: Fietze Ingo , Glos Martin , Moebus Isabel , Witt Christian , Penzel Thomas , Baumann Gert
Published: February 2007

Background: The optimal approach to initiate positive-pressure therapy in patients with obstructive sleep apnea is still debated. Current options are autotitrating positive airway pressure (APAP) or manual titration with continuous positive airway pressure (CPAP). Procedures differ by parameters and by algorithms used for adapting pressure. Objectives: To evaluate the efficacy of attended automatic titration in a randomized crossover study compared with manual titration over 2 nights where the sequence of the titration mode was changed. Therapy outcome was controlled after 6 weeks. Methods: 21 sleep apnea patients were treated using manual CPAP versus automatic APAP titration. The mode used during the 2nd night was continued for 6 weeks. Cardiorespiratory polysomnography, Epworth Sleepiness Scale (ESS), SF-36 score and compliance were assessed. Results: Apnea-hypopnea index reduction was equally effective at similar effective pressure independent of the titration mode. If APAP was applied during the 1st night, total sleep time was longer (384 vs. 331 min, p < 0.01) and sleep efficacy was higher (91 vs. 81%, p < 0.01) than after starting with manual titration with CPAP. Compliance was comparable in both groups (4.6 ± 1.9 h). The ESS improved in both groups (from 12.9 to 6.5). SF-36 scores and therapeutic pressure did not much change. Conclusions: Taking the sequence of titration into account, we found equal effectiveness of CPAP and APAP. Sleep quality was better with initial application of APAP – which favors attended automatic titration if only 1 titration night is possible. Both modes are comparable after 6 weeks regarding therapeutic pressure, efficacy, compliance and quality of life.
Cthrc1 Is a Novel Inhibitor of Transforming Growth Factor-β Signaling and Neointimal Lesion Formation
Authors: LeClair Renée J. , Durmus Tahir , Wang Qiaozeng , Pyagay Peter , Terzic Aleksandra , Lindner Volkhard
Published: February 2007

We identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene expressed in the adventitia and neointima on arterial injury and found that it functionally increases cell migration while reducing collagen deposition. To address the in vivo role of Cthrc1, we generated transgenic mouse lines that constitutively overexpress Cthrc1. An intercross of 2 transgenic lines produced offspring with brittle bones caused by a reduction in collagenous bone matrix. Hemizygous Cthrc1 transgenic mice developed normally but neointimal lesion formation and adventitial collagen deposition in response to carotid artery ligation were significantly reduced compared with wild-type littermates. In 75% of Cthrc1 transgenic mice, cartilaginous metaplasia of medial smooth muscle cells was observed as assessed by Alcian blue staining and expression of the chondrocyte marker collagen type II. Transforming growth factor-β signaling was reduced in smooth muscle cells of Cthrc1 transgenic arteries, as demonstrated by reduced phospho-Smad2/3 immunoreactivity, whereas Smad signaling related to bone morphogenetic proteins was unaffected. Similarly, primary smooth muscle cells and PAC1 smooth muscle cells overexpressing Cthrc1 had reduced levels of phospho-Smad2/3 as well as procollagen. Furthermore, Cthrc1 inhibited transforming growth factor-β–sensitive reporter constructs in smooth muscle but not endothelial cells. These data indicate that Cthrc1 is a cell-type–specific inhibitor of transforming growth factor-β, which in turn impacts collagen type I and III deposition, neointimal formation, and dedifferentiation of smooth muscle cells.
Ambulatory Arterial Stiffness Index and 24-Hour Ambulatory Pulse Pressure as Predictors of Mortality in Ohasama, Japan
Authors: Kikuya Masahiro , Staessen Jan A. , Ohkubo Takayoshi , Thijs Lutgarde , Metoki Hirohito , Asayama Kei , Obara Taku , Inoue Ryusuke , Li Yan , Dolan Eamon , Hoshi Haruhisa , Hashimoto Junichiro , Totsune Kazuhito , Satoh Hiroshi , Wang Ji-Guang , O’Brien Eoin , Imai Yutaka
Published: February 2007

Background and Purpose—

Ambulatory arterial stiffness index (AASI) and pulse pressure (PP) are indexes of arterial stiffness and can be computed from 24-hour blood pressure recordings. We investigated the prognostic value of AASI and PP in relation to fatal outcomes.

Methods—

In 1542 Ohasama residents (baseline age, 40 to 93 years; 63.4% women), we applied Cox regression to relate mortality to AASI and PP while adjusting for sex, age, BMI, 24-hour MAP, smoking and drinking habits, diabetes mellitus, and a history of cardiovascular disease.

Results—

During 13.3 years (median), 126 cardiovascular and 63 stroke deaths occurred. The sex- and age-standardized incidence rates of cardiovascular and stroke mortality across quartiles were U-shaped for AASI and J-shaped for PP. Across quartiles, the multivariate-adjusted hazard ratios for cardiovascular and stroke death significantly deviated from those in the whole population in a U-shaped fashion for AASI, whereas for PP, none of the HRs departed from the overall risk. The hazard ratios for cardiovascular mortality across ascending AASI quartiles were 1.40 (
P
=0.04), 0.82 (
P
=0.25), 0.64 (
P
=0.01), and 1.35 (
P
=0.03). Additional adjustment of AASI for PP and sensitivity analyses by sex, excluding patients on antihypertensive treatment or with a history of cardiovascular disease, or censoring deaths occurring within 2 years of enrollment, produced confirmatory results.

Conclusions—

In a Japanese population, AASI predicted cardiovascular and stroke mortality over and beyond PP and other risk factors, whereas in adjusted analyses, PP did not carry any prognostic information.
CT Angiography “Spot Sign” Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage
Authors: Wada Ryan , Aviv Richard I. , Fox Allan J. , Sahlas Demetrios J. , Gladstone David J. , Tomlinson George , Symons Sean P.
Published: February 2007

Background and Purpose—

Morbidity and mortality in spontaneous intracerebral hemorrhage (ICH) are correlated with hematoma progression. We hypothesized that the presence of tiny, enhancing foci (“spot sign”) within acute hematomas is associated with hematoma expansion.

Methods—

We prospectively studied 39 consecutive patients with spontaneous ICH by computed tomography angiography within 3 hours of symptom onset. Scans were reviewed by 3 readers. Patients were dichotomized according to the presence or absence of the spot sign. Clinical and radiological outcomes were compared between groups. The predictive value of this sign was assessed in a multivariate analysis.

Results—

Thirteen patients (33%) demonstrated 31 enhancing foci. Baseline clinical variables were similar in both groups. Hematoma expansion occurred in 11 patients (28%) on follow-up. Seventy-seven percent of patients with and 4% without hematoma expansion demonstrated the spot sign (
P
<0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for expansion were 91%, 89%, 77%, 96%, and 8.5, respectively. Interobserver agreement was high (κ=0.92 to 0.94). In patients with the spot sign, mean volume change was greater (
P
=0.008), extravasation more common (
P
=0.0005), and median hospital stay longer (
P
=0.04), and fewer patients achieved a good outcome (modified Rankin Scale score <2), although the latter was not significant (
P
=0.16). No differences in hydrocephalus (
P
=1.00), surgical intervention (
P
=1.00), or death (
P
=0.60) were noted between groups. In multiple regression, the spot sign independently predicted hematoma expansion (
P
=0.0003).

Conclusions—

The computed tomography angiography spot sign is associated with the presence and extent of hematoma progression. Fewer patients achieve a good clinical outcome and hospital stay was longer. Further studies are warranted to validate the ability of this sign to predict clinical outcomes.
Characterizing Tissue Fate After Transient Cerebral Ischemia of Varying Duration Using Quantitative Diffusion and Perfusion Imaging
Authors: Bardutzky Juergen , Shen Qiang , Henninger Nils , Schwab Stefan , Duong Timothy Q. , Fisher Marc
Published: February 2007

Background and Purpose—

The purpose of this study was to investigate the effects of reperfusion on ischemic lesion evolution and pixel-by-pixel apparent diffusion coefficient–cerebral blood flow (ADC-CBF) dynamics of core and mismatch tissues after 35, 60, and 95 minutes of transient focal ischemia in rats (n=28).

Methods—

Serial diffusion-, perfusion-, and T2-weighted imaging were performed up to 24 hours. The evolution of the magnetic resonance image-derived lesion volume was investigated and ADC-CBF scatterplots were performed to prospectively characterize the ADC and CBF dynamics of core and mismatch tissues with different fates. For comparison, similar analysis was performed on a historical 60-minute transient ischemia and permanent ischemia group.

Results—

ADC-derived lesions markedly decreased on reperfusion at 35 minutes to an average of 15±5% of prereperfusion lesion size (
P
<0.00001). At 24 hours, lesion volume as determined by T2 imaging increased again to 51±10% of prereperfusion lesion size. In the 95-minute group, ADC lesions only briefly decreased on reperfusion and then secondarily enlarged at 180 minutes, almost reaching prereperfusion lesion volume. Pixel-based analysis demonstrated that >85% of mismatch pixels were salvaged by reperfusion independent of ischemia duration. Recanalization at 35, 60, and 95 minutes resulted in recovery of 46%, 28%, and 9% of core pixels, respectively. Core and mismatch pixels that were ultimately salvaged had persistently higher (
P
<0.001) CBF values during ischemia in all reperfusion groups, associated with higher (
P
<0.05) ADC values.

Conclusion—

This study demonstrated substantial salvage of mismatch tissue after reperfusion independent of ischemia duration and substantial permanent recovery of initial core pixels with early reperfusion. Severity of CBF reduction during ischemia seems to be the main factor determining tissue fate.
Model-Based Linkage Analyses Confirm Chromosome 19q13.3 as a Susceptibility Locus for Intracranial Aneurysm
Authors: Mineharu Youhei , Inoue Kayoko , Inoue Sumiko , Yamada Shigeki , Nozaki Kazuhiko , Hashimoto Nobuo , Koizumi Akio
Published: February 2007

Background and Purpose—

In previous studies of familial intracranial aneurysm (IA), parametric linkage analyses have been undertaken for five unrelated families, four providing maximum logarithm of odds (LOD) scores with dominant models and one with a recessive model. Each family was linked to a distinct locus, indicating locus heterogeneity. This study aimed to examine whether Japanese IA families consistent with autosomal-dominant mode of inheritance support linkage to these loci.

Methods—

We performed genomewide linkage analysis using the GENEHUNTER program. Affected-only parametric linkage analysis was used for 41 affected members in nine unrelated IA families with dominant models, which were selected from 29 families used for a nonparametric (model-free) linkage analysis in our previous study.

Results—

We failed to support the linkage to previously reported autosomal-dominant loci. Instead, we found linkage to chromosome 19q13.3 with a maximum multipoint LOD score of 4.10. The LOD-1 interval (regions with LOD scores of >1) was 8.0 cM between D19S198 and D19S902.

Conclusions—

A genomewide scan for IA families with dominant models in Japan confirmed the locus at chromosome 19q13.3, which has also been reported as a candidate locus in a Finnish population.
Missed Diagnosis of Subarachnoid Hemorrhage in the Emergency Department
Authors: Vermeulen Marian J. , Schull Michael J.
Published: February 2007

Background and Purpose—

Subarachnoid hemorrhage (SAH) can be devastating, yet its initial presentation may be limited to common symptoms and subtle signs, potentially leading to misdiagnosis. Little is known about population rates of misdiagnosis of SAH, or hospital factors that may contribute to it. We estimated the population-based rate of missed SAH among emergency department (ED) patients and examined its relationship with hospital characteristics.

Methods—

We studied persons admitted with a nontraumatic SAH to all Ontario hospitals over 3 years (April 2002 to March 2005). SAH was defined as missed if the patient had an ED visit related to the SAH (based on a prespecified definition) in the 14 days before admission. We examined the association between hospital teaching status and missed SAH and explored whether annual ED volume of SAH or CT availability explained this association.

Results—

Of 1507 patients diagnosed with SAH, 5.4% (95% CI, 4.3 to 6.6) had a missed diagnosis. The risk was significantly higher among patients triaged as low acuity (odds ratio 2.65; 95% CI, 1.46 to 4.80), as well as in nonteaching hospitals (adjusted odds ratio 2.12; 95% CI, 1.02, 4.44). Neither ED SAH volume nor on-site CT availability explained the effect of teaching status.

Conclusions—

About 1 in 20 SAH patients are missed during an ED visit. Lower acuity patients are at higher risk of misdiagnosis, suggesting the need for heightened suspicion among patients with minimal clinical findings. The risk is also greater in nonteaching hospitals, but this is not explained by the annual volume of SAHs seen in the ED or access to CT.
The Relation Between Knowledge About Hypertension and Education in Hospitalized Patients With Stroke in Vienna
Authors: Samal Doris , Greisenegger Stefan , Auff Eduard , Lang Wilfried , Lalouschek Wolfgang
Published: February 2007

Background and Purpose—

Knowledge about hypertension and its control influences blood pressure control in patients with hypertension. We assessed these parameters in a large cohort of patients with ischemic stroke or transient ischemic attack and analyzed their association with educational attainment.

Methods—

Five hundred ninety-one consecutive patients with stroke with a medical history of hypertension were interviewed about knowledge concerning hypertension within a multicenter hospital-based stroke registry. We analyzed answers in relation to educational level with multivariate logistic regression adjusted for age and sex.

Results—

Seventy-seven percent of the patients stated to have known about hypertension being a risk factor for stroke, but only 30% felt at increased risk of stroke. Less than half (47%) could identify 140 mm Hg or less as the maximum tolerated systolic blood pressure, and 53% had their blood pressure only controlled monthly or less often. Knowledge of possible consequences of myocardial infarction, nephropathy, peripheral vascular disease, and retinopathy was 64%, 20%, 11%, and 16%, respectively. Approximately half of patients were acquainted with the nonpharmacologic treatment options of physical activity (49%), reduction of salt intake (54%), and reduction of caloric intake (48%), whereas relaxation techniques were only known to 17%. Adherence to those treatment options ranged from 42% to 67%. Educational level was significantly associated with knowledge of increased risk, possible consequences of hypertension, and knowledge about nonmedication treatment options.

Conclusion—

Knowledge in our population was insufficient and partly associated with educational level, leaving much room for improvement by educational campaigns. Furthermore, we found a gap between knowledge of the increased risk for stroke in patients with hypertension and awareness of their own risk.
Blood Pressure and Estimated Risk of Stroke in the Elderly Population of Spain
Authors: Redón Josep , Cea-Calvo Luis , Lozano José V. , Martí-Canales Juan C. , Llisterri José L. , Aznar Jose , González-Esteban Jorge
Published: February 2007

Background and Purpose—

The objective of this study was to estimate the high blood pressure values and the 10-year risk of stroke in the Spanish general population aged 60 years or older using the Framingham scale.

Methods—

This was a multicenter, population-based, cross-sectional study performed in Spanish primary care centers. A randomized selection of centers and recruitment population was used. We collected clinical, biochemical, and electrocardiographic data.

Results—

We analyzed 7343 subjects (mean age, 71.6 years; standard deviation, 7.0; 53.4% females, 34.4% obese subjects, and 27.1% diabetic subjects). Electrocardiographic–left ventricle hypertrophy was present in 12.9% of the subjects, atrial fibrillation in 8.4%, and established cardiovascular disease in 28.9%; 73.0% already had hypertension diagnosed, and 12.8% showed high blood pressure without a prior diagnosis of hypertension. Among hypertensive subjects, 29.1% had high blood pressure on therapeutic objective, and of the total population 35.7% had high blood pressure under control. Those with hypertension already diagnosed showed a higher prevalence of other stroke risk factors (left ventricle hypertrophy, atrial fibrillation, diabetes, or established cardiovascular disease). The estimated 10-year stroke risk was 19.6% (standard deviation, 17.3%), and was greater in hypertensive patients (23.7%; standard deviation, 18.5) than in patients with high blood pressure without known hypertension (12.4%; standard deviation, 9.2), or in normotensive subjects (5.3%; standard deviation, 0.2;
P
<0.001).

Conclusion—

The 10-year estimated stroke risk was 19.6%, and it was greater in hypertensive patients as compared with the remainder people at any blood pressure range. The concomitant stroke risk factors are more prevalent in patients with hypertension already diagnosed, which implies an important additional estimated risk of stroke.
Morphological Observation and In Vitro Angiogenesis Assay of Endothelial Cells Isolated From Human Cerebral Cavernous Malformations
Authors: Zhao Yao , Tan Yu-Zhen , Zhou Liang-Fu , Wang Hai-Jie , Mao Ying
Published: February 2007

Background and Purpose—

Little is known about the role of endothelial cells (ECs) in the pathogenesis of cerebral cavernous malformation because of the difficulties to obtain highly pure ECs. Thus, this study attempted to establish a reliable procedure to isolate and culture ECs from human cerebral cavernous malformation lesions. The biological features and the angiogenic potential of the cultured ECs were also investigated.

Methods—

A modified protocol was developed to isolate and culture cerebral cavernous malformation endothelial cells (CECs)from surgically resected human specimens. The biological features of CECs were investigated by electron microscope, immunostaining, real-time polymerase chain reaction, fluorescence-activated cell sorter, and Western blotting. The tube formation by CECs was examined in an in vitro angiogenesis model with or without the addition of vascular endothelial growth factor.

Results—

CECs from the specimens unaffected by the intraoperative bipolar coagulation were cultivated successfully with higher than 95% purity. Comparing to the ECs from control brain tissue, CECs presented primitive nucleus in ultrathin section, expressed higher levels of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, and spontaneously formed tube structures in a 3-dimensional collagen matrix. The tube formation by CECs was significantly promoted by vascular endothelial growth factor treatment.

Conclusions—

A modified protocol for the attainment of purified CECs and the first in vitro angiogenesis model of CECs were successfully established. We provided initial evidence that CECs had enhanced angiogenic potential and showed increased responsiveness to vascular endothelial growth factor.
Altered Retrobulbar Hemodynamics in Patients Who Have Transient Monocular Blindness Without Carotid Stenosis
Authors: Chao A-Ching , Hsu Hung-Yi , Chung Chih-Ping , Chen Yen-Yu , Yen May-Yung , Wong Weng-Jang , Hu Han-Hwa
Published: February 2007

Background and Purpose—

This study was to evaluate the retrobulbar hemodynamics in patients who have transient monocular blindness (TMB) without carotid stenosis.

Methods—

Fifty-nine patients who have TMB without carotid stenosis were studied along with 59 age- and sex-matched controls. Color Doppler–imaging was used to study the retrobulbar hemodynamic by measuring the flow velocities (peak-systolic velocity, and end-diastolic velocity), vascular resistance indices (pulsatility index, and resistance index) in central retinal arteries, short posterior ciliary arteries, and ophthalmic arteries. The patients were divided into 2 groups according to the attack frequency: group 1 (occasional TMB, 2 or fewer attacks, 26 patients) and group 2 (frequent TMB, 3 or more attacks, 33 patients).

Results—

The risk factors for atherosclerosis were similar between the cases and controls. The means of end-diastolic velocity were significantly lower in central retinal arteries and ophthalmic arteries, and the pulsatility index and resistance index were significantly higher in all the 3 retrobulbar vessels in TMB patients than for the controls. The differences between patients and controls were greater for the group-2 patients.

Conclusion—

Patients who have TMB without carotid stenosis had altered retrobulbar hemodynamics with a generalized increase in vascular resistance in the retrobulbar arteries. The role of venous hypertension as an etiology needs further study.
Targeting Ligand-Induced Binding Sites on GPIIb/IIIa via Single-Chain Antibody Allows Effective Anticoagulation Without Bleeding Time Prolongation
Authors: Stoll Patrick , Bassler Nicole , Hagemeyer Christoph E. , Eisenhardt Steffen U. , Chen Yung Chih , Schmidt Rene , Schwarz Meike , Ahrens Ingo , Katagiri Yasuhiro , Pannen Benedikt , Bode Christoph , Peter Karlheinz
Published: February 2007

Objective—Therapeutic anticoagulation is widely used, but limitations in efficacy and bleeding complications cause an ongoing search for new agents. However, with new agents developed it seems to be an inherent problem that increased efficiency is accompanied by an increase in bleeding complications. We investigate whether targeting of anticoagulants to activated platelets provides a means to overcome this association of potency and bleeding.

Methods and Results—Ligand-induced binding sites (LIBS) on fibrinogen/fibrin-binding GPIIb/IIIa represent an abundant clot-specific target. We cloned an anti-LIBS single-chain antibody (scFvanti-LIBS) and genetically fused it with a potent, direct factor Xa (fXa) inhibitor, tick anticoagulant peptide (TAP). Specific antibody binding of fusion molecule scFvanti-LIBS-TAP was proven in flow cytometry; anti-fXa activity was demonstrated in chromogenic assays. In vivo anticoagulative efficiency was determined by Doppler-flow in a ferric chloride–induced carotid artery thrombosis model in mice. ScFvanti-LIBS-TAP prolonged occlusion time comparable to enoxaparine, recombinant TAP, and nontargeted mutant-scFv-TAP. ScFvanti-LIBS-TAP revealed antithrombotic effects at low doses at which the nontargeted mutant-scFv-TAP failed. In contrast to the other anticoagulants tested, bleeding times were not prolonged by scFvanti-LIBS-TAP.

Conclusions—The novel clot-targeting approach of anticoagulants via single-chain antibody directed against a LIBS-epitope on GPIIb/IIIa promises effective anticoagulation with reduced bleeding risk.
Predominance of a Proinflammatory Phenotype in Monocyte-Derived Macrophages From Subjects With Low Plasma HDL-Cholesterol
Authors: Sarov-Blat Lea , Kiss Robert S. , Haidar Bassam , Kavaslar Nihan , Jaye Michael , Bertiaux Melissa , Steplewski Klaudia , Hurle Mark R. , Sprecher Dennis , McPherson Ruth , Marcel Yves L.
Published: February 2007

Objective—

Reduced plasma concentrations of high-density lipoprotein-cholesterol (HDL-C) are a significant risk factor for cardiovascular disease. Mechanisms that regulate HDL-C concentrations represent an important area of investigation.

Methods and Results—

Comparative transcriptome analyses of monocyte-derived macrophages (MDM) from a large population of low HDL-C subjects and age- and sex-matched controls revealed a cluster of inflammatory genes highly expressed in low HDL-C subjects. The expression levels of peroxisome proliferator activated receptor (PPAR) γ and several antioxidant metallothionein genes were decreased in MDM from all low HDL-C groups compared with controls, as was the expression of other genes regulated by PPARγ, including CD36, adipocyte fatty acid binding protein (FABP4), and adipophilin (ADFP). In contrast, PPARδ expression was increased in MDM from low HDL-C groups. Quantitative RT-PCR corroborated all major findings from the microarray analysis in two separate patient cohorts. Expression of several inflammatory cytokine genes including interleukin 1β, interleukin 8, and tumor necrosis factor α were highly increased in low HDL-C subjects.

Conclusions—

The activated proinflammatory state of monocytes and MDM in low HDL-C subjects constitutes a novel parameter of risk associated with HDL deficiency, related to altered expression of metallothionein genes and the reciprocal regulation of PPARγ and PPARδ.
P-Selectin Glycoprotein Ligand-1 Is Expressed on Endothelial Cells and Mediates Monocyte Adhesion to Activated Endothelium
Authors: da Costa Martins Paula , García-Vallejo Juan-Jesús , van Thienen Johannes V. , Fernandez-Borja Mar , van Gils Janine M. , Beckers Cora , Horrevoets Anton J. , Hordijk Peter L. , Zwaginga Jaap-Jan
Published: February 2007

Objective—

The purpose of this study was to investigate the presence and functionality of P-selectin glycoprotein ligand-1 (PSGL-1) on activated endothelial cells (ECs).

Methods and Results—

We show here that PSGL-1 is expressed at the mRNA and protein levels in umbilical vein and microvascular ECs. Furthermore, this endothelial PSGL-1 (ePSGL-1) is functional and mediates adhesion of monocytes or platelet-monocyte complexes (PMCs) to the activated endothelium in a flow model. ePSGL-1 expression was not affected by treating ECs with inflammatory stimuli (tumor necrosis factor α, interleukin-1β, thrombin, or histamine). However, the functional binding capacity of ePSGL-1 to monocytes or P-selectin/Fc chimera significantly increased by stimulation of the ECs with TNFα. By means of a siRNA approach to specifically knock-down the genes involved in the glycosylation of PSGL-1 we could show that tumor necrosis factor α–induced glycosylation of ePSGL-1 is critical for its binding capacity.

Conclusion—

Our results show that ECs express functional PSGL-1 which mediates tethering and firm adhesion of monocytes and platelets to inflamed endothelium.
Pair duets in the yellow-naped amazon (Amazona auropalliata): Phonology and syntax
Authors: Dahlin Christine , Wright Timothy
Published: February 2007

Pair duets are acoustically complex communication signals formed jointly by members of a mated pair. Duets may serve multiple communication functions; quantitative studies of the acoustic structure and organization of notes (or 'syntax') within duets are an important step in identifying these functions. This study examined duets of the yellow-naped amazon (Amazona auropalliata) at two sites in Costa Rica to determine the syntactical rules underlying duet variation. Duets were composed of contact calls and three other note types found only in duets. These latter note types were sex-specific, with one type performed by females and the other two types by males. Sex-specific notes were delivered antiphonally and in distinct pairs, with the male note following and often overlapping that of the female. Note types appeared in a strict sequential order in which each note could be repeated a variable number of times or omitted entirely, a pattern previously termed 'combinatorial syntax'. Additionally, there was considerable variation in acoustic parameters of notes within types. Many of these parameters varied significantly with note order within a duet. These syntactical features suggest a preliminary hypothesis that males and females encode different, and possibly multiple, messages in their respective contributions to duets.
Predictive Population Pharmacokinetic/Pharmacodynamic Model for a Novel COX‐2 Inhibitor
Authors: Rohatagi S. , Kastrissios H. , Gao Y. , Zhang N. , Xu J. , Moberly J. , Wada R. , Yoshihara K. , Takahashi M. , Truitt K. , Salazar D.
Published: February 2007

The objectives of these analyses were to (1) develop a population pharmacokinetic/pharmacodynamic model for a novel COX‐2 inhibitor (CS‐706) using data from primarily Caucasian subjects, (2) predict responses in subpopulations of interest (including Japanese subjects), and (3) correlate pharmacodynamic parameters to safety outcomes. The model was developed using data from 130 healthy adults following single or multiple doses of CS‐706. Serial plasma concentrations of CS‐706 and ex vivo whole‐blood cyclooxygenase‐1 (COX‐1) and COX‐2 activity were determined up to 72 hours postdose. An Emax model described relationships between CS‐706 plasma concentrations and COX‐1 and COX‐2 inhibition. CS‐706 potency (EC50) was 397 ng/mL for COX‐1 and 20 ng/mL for COX‐2. None of the tested covariates influenced the pharmacodynamics of CS‐706. Japanese subjects are expected to show a slightly reduced response to CS‐706, consistent with lower exposure following the same dose given to Caucasian subjects. Predictive pharmacokinetic/pharmacodynamic modeling for COX‐1 and COX‐2 inhibition indicates a 20‐fold potency ratio that is expected to be similar in Japanese and Caucasians. There was good correlation between COX‐1 inhibition and the incidence of 7‐day gastroduodenal mucosal injury. A dose of less than 25 mg bid could be adequate to inhibit COX‐2 activity with a low risk of gastrointestinal mucosal injury.
Is Once‐Daily Mesalazine Equivalent to the Currently Used Twice‐Daily Regimen? A Study Performed in 30 Healthy Volunteers
Authors: Gandia Peggy , Idier Isabelle , Houin Georges
Published: February 2007

A randomized, 2‐way, crossover study was conducted in 30 volunteers to compare the pharmacokinetic profile of a new once‐daily dosing regimen of mesalazine (1 × 4 g/d) with the current twice‐daily dosage (2 × 2 g/d) used in many European countries. The 2 dosages were administrated orally for 8 days, separated by a 2‐week washout. Plasma concentrations of mesalazine and N‐acetyl‐mesalazine were determined on days 1 and 8 by a validated high‐performance liquid chromatography method and Cmax, tmax, and AUCs calculated. The bioequivalence was obtained for a 90% confidence interval of the AUC0–24hratio (test/reference) for mesalazine and N‐acetyl‐mesalazine on days 1 and 8, within the range of 0.80 to 1.25. The bioequivalence was demonstrated on day 1 for mesalazine and N‐acetyl‐mesalazine and on day 8 for mesalazine. As it is desirable to offer patients a preparation with a less frequent administration to enhance compliance, this once‐daily regimen may be an attractive dosing option.
Absolute and Relative Bioavailability of Fentanyl Buccal Tablet and Oral Transmucosal Fentanyl Citrate
Authors: Darwish Mona , Kirby Mary , Robertson Philmore , Tracewell William , Jiang John G.
Published: February 2007

This study assessed the absolute and relative bioavailabilities and transmucosal and gastrointestinal absorbency of fentanyl buccal tablet (FBT) and oral transmucosal fentanyl citrate (OTFC). In a randomized crossover design, 26 healthy subjects received FBT 400 μg (transmucosal), FBT 800 μg (oral), OTFC 800 μg (transmucosal), and fentanyl 400 μg (intravenous). The transmucosal FBT had the highest absolute bioavailability (0.65) compared with the oral FBT (0.31) or transmucosal OTFC (0.47). More fentanyl was absorbed transmucosally from FBT than OTFC (48% vs 22%). Median tmax values were shorter following the transmucosal FBT (47 minutes) than the oral FBT (90 minutes) or the transmucosal OTFC (91 minutes). Transmucosal administration of FBT compared with dose‐normalized OTFC resulted in higher total systemic fentanyl exposure, higher early systemic exposure, and higher Cmax. The rate and extent of fentanyl absorption were greater following administration of FBT compared to OTFC. An approximately 30% smaller dose of FBT achieved systemic exposures comparable to OTFC.
A 6-Year Follow-up of the Effect of Graft Site on Strength, Stability, Range of Motion, Function, and Joint Degeneration after Anterior Cruciate Ligament Reconstruction
Authors: Keays Susan L. , Bullock-Saxton Joanne E. , Keays Anthony C. , Newcombe Peter A. , Bullock Margaret I.
Published: February 2007

Background

The choice of graft material for anterior cruciate ligament reconstruction remains controversial. Despite the need for well-controlled, long-term outcome studies comparing patellar tendon with hamstring grafting, few studies have followed results for more than 5 years.

Hypothesis

Graft source will not affect outcome 6 years after reconstruction.

Study Design

Cohort study; Level of evidence, 2.

Methods

Sixty-two patients with anterior cruciate ligament reconstruction and 18 uninjured control subjects were studied over 6 years. Thirty-one patients received patellar tendon grafts, and 31 received hamstring tendon grafts. Assessment included knee joint stability, range of motion, muscle strength, subjective function, objective function (running, sidestepping, carioca, and hop tests), and joint degeneration.

Results

Clinical stability was restored to all patients other than to the 2 hamstring graft recipients who suffered reinjuries. The KT-1000 arthrometer side-to-side differences were similar in the patellar tendon (1.9 mm) and hamstring tendon (2.0 mm) groups but were significantly greater than that of uninjured control subjects (P < .001). There were no significant strength differences between surgical and control groups, although a 6% quadriceps deficit existed after patellar tendon grafting. In the more demanding functional tests (hop and triple-hop indices and carioca), the hamstring graft recipients performed similarly to the control group, whereas a significant difference (P < .05) existed between the patellar tendon graft and the control group. The incidence of early tibiofemoral osteoarthritis was significantly greater after reconstruction using patellar tendon (62%) than after hamstring tendon grafting (33%; P = .002).

Conclusion

Six-year outcomes were very satisfactory irrespective of graft source. However, reconstruction using the hamstring tendons resulted in improved functional performance and a lower incidence of osteoarthritis.
Biomechanical Evaluation of Minimally Invasive Repairs for Complete Acromioclavicular Joint Dislocation
Authors: Wellmann Mathias , Zantop Thore , Weimann Andre , Raschke Michael J. , Petersen Wolf
Published: February 2007

Background

The conventional coracoclavicular ligament augmentation with a single polydioxanone loop has been shown to have some pivotal disadvantages.

Hypothesis

A minimally invasive flip button/polydioxanone repair provides similar biomechanical properties to the conventional polydioxanone cerclage around the coracoid. However, the authors expected a difference in linear stiffness, ultimate load, and permanent elongation between suture anchor repairs and polydioxanone repairs.

Study Design

Controlled laboratory study.

Methods

The tensile fixation strength of 4 different minimally invasive repairs was tested in a porcine metatarsal model: (1) 1.3-mm single polydioxanone cerclage with a subcoracoidal flip button fixation, (2) 1.3-mm single polydioxanone cerclage, (3) Twinfix Ti 3.5-mm/Ultrabraid 2-suture anchor, and (4) Twinfix Ti 5.0-mm/Ultrabraid 2-suture anchor. The testing protocol included cyclic superoinferior loading and a subsequent load to failure trial.

Results

The flip button repair (646 N) and the conventional polydioxanone banding (663 N) revealed significant higher ultimate loads than did the suture anchor repairs (295 and 331 N, respectively; P < .001), whereas no significant differences were found for the elongation behavior under cyclic loading.

Conclusion

There was no significant difference between the 2 polydioxanone repairs. The ultimate load of the flip button procedure reaches the level of the native coracoclavicular ligament complex as it has been quantified in the literature.

Clinical Relevance

Although the biomechanical results comparing a minimally invasive flip button procedure versus a conventional polydioxanone cerclage are similar, the authors recommend the flip button procedure because of its minimally invasive approach and the secure subcoracoidal fixation technique with a minimized risk of anterior loop dislocation and neurovascular damage.
Engaging Men and Boys in Preventing Violence Against Women
Authors: Crooks Claire V. , Goodall George R. , Hughes Ray , Jaffe Peter G. , Baker Linda L.
Published: February 2007

Although historically the prevention of relationship violence has been seen as a women's issue, more recently recognition has emerged regarding the need to engage men as partners in these initiatives. Early attempts have been mainly driven by grassroots efforts and have not been consistent with a particular theory of behavior and attitude change. This article investigates the application of cognitive–behavioral strategies to engaging men and boys in violence prevention, within a profeminist framework. Three fundamental components of a cognitive–behavioral therapy approach—goal setting, core beliefs, and strategies for change—are discussed and examples of promising initiatives are used to highlight these ideas.
Differing Effects of Partner and Nonpartner Sexual Assault on Women's Mental Health
Authors: Temple Jeff R. , Weston Rebecca , Rodriguez Benjamin F. , Marshall Linda L.
Published: February 2007

This study contrasted the effects of intimate partner and nonpartner sexual assault on women's mental health among a sample ( N = 835) of low-income, ethnically diverse community women. Compared to sexual assault by a previous partner or by a non-intimate partner, sexual assault by a current partner was the strongest predictor of PTSD, stress, and dissociation. Non–intimate partner sexual assault was only a significant predictor of PTSD and only for African American women. These findings suggest that the victim-offender relationship is important when considering the impact of sexual assault. Specifically, sexual assault perpetrated by an intimate partner may be especially traumatic.
No Refuge
Authors: Rasmussen Brian
Published: February 2007

This exploratory survey examined the dreams, nightmares, and sleep patterns of 30 women who were dealing with relationship violence. The sample of women was taken from two transition homes and a family counseling center. The findings indicate that 50% of the sample experienced nightmares on a weekly basis. Some of the dream images included drowning, being chased, being killed, or killing others. Slightly more than half (56%) experienced a recurring dream. Most women had trouble falling asleep and, on average, slept for 6.1 hours per night. Implications for practice and future research are discussed.