bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardioprotection initiated by reactive oxygen species is dependent on activation of PKCε
Authors: Kabir Alamgir M. N. , Clark James E. , Tanno Masaya , Cao Xuebin , Hothersall John S. , Dashnyam Semjidmaa , Gorog Diana A. , Bellahcene Mohamed , Shattock Michael J. , Marber Michael S.
Published: May 2006

To examine whether cardioprotection initiated by reactive oxygen species (ROS) is dependent on protein kinase Cε (PKCε), isolated buffer-perfused mouse hearts were randomized to four groups: 1) antimycin A (AA) (0.1 μg/ml) for 3 min followed by 10 min washout and then 30 min global ischemia (I) and 2 h reperfusion (R); 2) controls of I/R alone; 3) AA bracketed with 13 min of N-2-mercaptopropionyl- glycine (MPG) followed by I/R; and 4) MPG (200 μM) alone, followed by I/R. Isolated adult rat ventricular myocytes (ARVM) were exposed to AA (0.1 μg/ml), and lucigenin was used to measure ROS production. Murine hearts and ARVM were exposed to AA (0.1 μg/ml) with or without MPG, and PKCε translocation was measured by cell fractionation and subsequent Western blot analysis. Finally, the dependence of AA protection on PKCε was determined by the use of knockout mice (−/−) lacking PKCε. AA exposure caused ROS production, which was abolished by the mitochondrial uncoupler mesoxalonitrile 4-trifluoromethoxyphenylhydrazone. In addition, AA significantly reduced the percent infarction-left ventricular volume compared with control I/R (26 ± 4 vs. 43 ± 2%; P < 0.05). Bracketing AA with MPG caused a loss of protection (52 ± 7 vs. 26 ± 4%; P < 0.05). AA caused PKCε translocation only in the absence of MPG, and protection was lost on the pkcε−/− background (38 ± 3 vs. 15 ± 4%; P < 0.001). AA causes ROS production, on which protection and PKCε translocation depend. In addition, protection is absent in PKCε null hearts. Our results imply that, in common with ischemic preconditioning, PKCε is crucial to ROS-mediated protection.
Ontogeny of excitatory and inhibitory control of gastrointestinal motility in the African clawed frog,Xenopus laevis
Authors: Sundqvist Monika , Holmgren Susanne
Published: May 2006

The transparent body wall of Xenopus laevis larvae during the first developmental stages allows in vivo studies of gastrointestinal tract activity. The purpose of this study was to chart the ontogeny of gut motility in Xenopus larvae and to identify the most important control systems during the first developmental stages. Coordinated descending contraction waves first occurred in the gut at Nieuwkoop and Faber stage 43 [0.8 ± 0.1 contractions/min (cpm)] and increased to 4.9 ± 0.1 cpm at stage 47. The cholinergic receptor agonist carbachol (5–10 μM) increased contraction frequency already at stage 43, as did neurokinin A (NKA, 0.3–1 μM). The muscarinic antagonist atropine (100 μM) first affected contraction frequency at stage 45, which coincides with the onset of feeding. The tachykinin antagonist MEN-10,376 (6 μM) blocked NKA-induced contractions but not spontaneous motility. Both sodium nitroprusside [nitric oxide (NO) donor, 1–10 μM] and vasoactive intestinal peptide (VIP, 0.1–1 μM) inhibited contractions from the earliest stage onward. Blocking NO synthesis using NG-nitro-l-arginine methyl ester (100 μM) had no effect per se, but antagonized VIP evoked inhibition at stage 47. We conclude that gastrointestinal motility is well developed in the Xenopus laevis larvae before the onset of feeding. Functional muscarinic and tachykinin receptors are present already at the onset of motility, whereas a cholinergic tone develops around the onset of feeding. No endogenous tachykinin tone was found. Functional VIP receptors mediate inhibition at the onset of motility. NO seems to mediate the VIP effect at later stages.
Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are Clock independent
Authors: Kennaway David J. , Owens Julie A. , Voultsios Athena , Varcoe Tamara J.
Published: May 2006

The circadian rhythmicity of hormone secretion, body temperature, and sleep/wakefulness results from an endogenous rhythm of neural activity generated by clock genes in the suprachiasmatic nucleus (SCN). One of these genes, Clock, has been considered essential for the generation of cellular rhythmicity centrally and in the periphery; however, melatonin-proficient ClockΔ19 + MEL mutant mice retain melatonin rhythmicity, suggesting that their central rhythmicity is intact. Here we show that melatonin production in these mutants was rhythmic in constant darkness and could be entrained by brief single daily light pulses. Under normal light-dark conditions, per2 and prokineticin2 ( PK2) mRNA expression was rhythmic in the SCN of ClockΔ19 + MEL mice. Expression of Bmal1 and npas 2 was not altered, whereas per1 expression was arrhythmic. In contrast to the SCN, per1 and per2 expression, as well as Bmal1 expression in liver and skeletal muscle, together with plasma corticosterone, was arrhythmic in ClockΔ19 + MEL mutant mice in normal light-dark conditions. npas2 mRNA was also arrhythmic in liver but rhythmic in muscle. The ClockΔ19 mutation does not abolish central rhythmicity and light entrainment, suggesting that a functional Clock homolog, possibly npas2, exists in the SCN. Nevertheless, the SCN of ClockΔ19 + MEL mutant mice cannot maintain liver and muscle rhythmicity through rhythmic outputs, including melatonin secretion, in the absence of functional Clock expression in the tissues. Therefore, liver and muscle, but not SCN, have an absolute requirement for CLOCK, with as yet unknown Clock-independent factors able to generate the latter.
Ouabain-sensitive bicarbonate secretion and acid absorption by the marine teleost fish intestine play a role in osmoregulation
Authors: Grosell M. , Genz J.
Published: May 2006

The gulf toadfish ( Opsanus beta) intestine secretes base mainly in the form of HCO3−via apical anion exchange to serve Cl−and water absorption for osmoregulatory purposes. Luminal HCO3−secretion rates measured by pH-stat techniques in Ussing chambers rely on oxidative energy metabolism and are highly temperature sensitive. At 25°C under in vivo-like conditions, secretion rates averaged 0.45 μmol·cm−2·h−1, of which 0.25 μmol·cm−2·h−1can be accounted for by hydration of endogenous CO2partly catalyzed by carbonic anhydrase. Complete polarity of secretion of HCO3−and H+arising from the CO2hydration reaction is evident from equal rates of luminal HCO3−secretion via anion exchange and basolateral H+extrusion. When basolateral H+extrusion is partly inhibited by reduction of serosal pH, luminal HCO3−secretion is reduced. Basolateral H+secretion occurs in exchange for Na+via an ethylisopropylamiloride-insensitive mechanism and is ultimately fueled by the activity of the basolateral Na+-K+-ATPase. Fluid absorption by the toadfish intestine to oppose diffusive water loss to the concentrated marine environment is accompanied by a substantial basolateral H+extrusion, intimately linking osmoregulation and acid-base balance.
Effects of prior exercise and a low-carbohydrate diet on muscle sarcoplasmic reticulum function during cycling in women
Authors: Duhamel T. A. , Green H. J. , Perco J. G. , Ouyang J.
Published: May 2006

The effects of exercise and diet on sarcoplasmic reticulum Ca2+-cycling properties in female vastus lateralis muscle were investigated in two groups of women following four different conditions. The conditions were 4 days of a low-carbohydrate (Lo CHO) and glycogen-depleting exercise plus a Lo CHO diet (Ex + Lo CHO) ( experiment 2) and 4 days of normal CHO (Norm CHO) and glycogen-depleting exercise plus Norm CHO (Ex + Norm CHO) ( experiment 1). Peak aerobic power (V̇o2peak) was 38.1 ± 1.4 (SE); n = 9 and 35.6 ± 1.4 ml·kg−1·min−1; n = 9, respectively. Sarcoplasmic reticulum properties measured in vitro in homogenates (μmol·g protein−1·min−1) indicated exercise-induced reductions ( P < 0.05) in maximal Ca2+-ATPase activity (0 > 30, 60 min > fatigue), Ca2+uptake (0 > 30 > 60 min, fatigue), and Ca2+release, both phase 1 (0, 30 > 60 min, fatigue) and phase 2 (0 > 30, 60 min, fatigue; 30 min > fatigue) in Norm CHO. Exercise was without effect in altering the Hill slope ( nH), defined as the slope of relationship between Ca2+-ATPase activity and Ca2+concentration. No differences were observed between Norm CHO and Ex+Norm CHO. Compared with Norm CHO, Lo CHO resulted in a lower ( P < 0.05) Ca2+uptake, phase 1 Ca2+release (30 min), and nH. Ex + Lo CHO resulted in a greater ( P < 0.05) Ca2+uptake and nHcompared with Lo CHO. The results demonstrate that Lo CHO alone can disrupt SR Ca2+cycling and that, with the exception of Ca2+release, a glycogen-depleting session of exercise before Lo CHO can reverse the effects.
Respiratory responses to cold water immersion: neural pathways, interactions, and clinical consequences awake and asleep
Authors: Datta Avijit , Tipton Michael
Published: May 2006

The ventilatory responses to immersion and changes in temperature are reviewed. A fall in skin temperature elicits a powerful cardiorespiratory response, termed “cold shock,” comprising an initial gasp, hypertension, and hyperventilation despite a profound hypocapnia. The physiology and neural pathways of this are examined with data from original studies. The respiratory responses to skin cooling override both conscious and other autonomic respiratory controls and may act as a precursor to drowning. There is emerging evidence that the combination of the reestablishment of respiratory rhythm following apnea, hypoxemia, and coincident sympathetic nervous and cyclic vagal stimulation appears to be an arrhythmogenic trigger. The potential clinical implications of this during wakefulness and sleep are discussed in relation to sudden death during immersion, underwater birth, and sleep apnea. A drop in deep body temperature leads to a slowing of respiration, which is more profound than the reduced metabolic demand seen with hypothermia, leading to hypercapnia and hypoxia. The control of respiration is abnormal during hypothermia, and correction of the hypoxia by inhalation of oxygen may lead to a further depression of ventilation and even respiratory arrest. The immediate care of patients with hypothermia needs to take these factors into account to maximize the chances of a favorable outcome for the rescued casualty.
Glucose kinetics differ between women and men, during and after exercise
Authors: Horton Tracy J. , Grunwald Gary K. , Lavely Jennifer , Donahoo W. Troy
Published: May 2006

As exercise can improve the regulation of glucose and carbohydrate metabolism, it is important to establish biological factors, such as sex, that may influence these outcomes. Glucose kinetics, therefore, were compared between women and men at rest, during exercise, and postexercise. It was hypothesized that glucose flux would be significantly lower in women than men during both the exercise and postexercise periods. Subjects included normal weight, healthy, eumenorrehic women and men, matched for habitual activity level and maximal oxygen uptake per kilogram lean body mass. Testing occurred following 3 days of diet control, with no exercise the day before. Subjects were tested in the overnight-fasted condition with women studied in the midluteal phase of the menstrual cycle. Resting (120 min), exercise (85% lactate threshold, 90 min), and postexercise (180 min) measurements of glucose flux and substrate metabolism were made. During exercise, women had a significantly lower rate of glucose appearance (Ra) ( P < 0.001) and disappearance (Rd) ( P < 0.002) compared with men. Maximal values were achieved at 90 min of exercise for both glucose Ra (mean ± SE: 22.8 ± 1.12 μmol·kg body wt−1·min−1 women and 33.6 ± 1.79 μmol·kg body wt−1·min−1 men) and glucose Rd (23.2 ± 1.26 and 34.1 ± 1.71 μmol·kg body wt−1·min−1, respectively). Exercise epinephrine concentration was significantly lower in women compared with men ( P < 0.02), as was the increment in glucagon from rest to exercise ( P < 0.04). During the postexercise period, glucose Ra and Rd were also significantly lower in women vs. men ( P < 0.001), with differences diminishing over time. In conclusion, circulating blood glucose flux was significantly lower during 90 min of moderate exercise, and immediately postexercise, in women compared with men. Sex differences in the glucagon increase to exercise, and/or the epinephrine levels during exercise, may play a role in determining these sex differences in exercise glucose turnover.
Pharyngeal critical pressure in children with mild sleep-disordered breathing
Authors: Fregosi R. F. , Quan S. F. , Morgan W. L. , Goodwin J. L. , Cabrera R. , Shareif I. , Fridel K. W. , Bootzin R. R.
Published: May 2006

There is evidence that narrowing or collapse of the pharynx can contribute to obstructive sleep-disordered breathing (SDB) in adults and children. However, studies in children have focused on those with relatively severe SDB who generally were recruited from sleep clinics. It is unclear whether children with mild SDB who primarily have hypopneas, and not frank apnea, also have more collapsible airways. We estimated airway collapsibility in 10 control subjects (9.4 ± 0.5 yr old; 1.9 ± 0.2 hypopneas/h) and 7 children with mild SDB (10.6 ± 0.5 yr old; 11.5 ± 0.1 hypopneas/h) during stable, non-rapid eye movement sleep. None of the subjects had clinically significant enlargement of the tonsils or adenoids, nor had any undergone previous tonsillectomy or adenoidectomy. Airway collapsibility was measured by brief (2-breath duration) and sudden reductions in pharyngeal pressure by connecting the breathing mask to a negative pressure source. Negative pressure applications ranging from −1 to −20 cmH2O were randomly applied in each subject while respiratory airflow and mask pressure were measured. Flow-pressure curves were constructed for each subject, and the x-intercept gave the pressure at zero flow, the so-called critical pressure of the upper airway (Pcrit). Pcrit was significantly higher in children with SDB than in controls (−10.8 ± 2.8 vs. −15.7 ± 1.2 cmH2O; P < 0.05). There were no significant differences in the slopes of the pressure-flow relations or in baseline airflow resistance. These data support the concept that intrinsic pharyngeal collapsibility contributes to mild SDB in children.
Preserved autonomic function in amenorrheic athletes
Authors: Wenner Megan M. , Prettyman Allen V. , Maser Raelene E. , Farquhar William B.
Published: May 2006

Reproductive hormones such as estradiol and progesterone are known to influence autonomic cardiovascular regulation. The purpose of this study was to determine whether amenorrheic athletes (AA) have impaired autonomic cardiovascular regulation compared with eumenorrheic athletes (EA). Thirty-five athletes were tested: 13 AA (19 ± 1 yr), 13 EA (21 ± 1 yr), and 9 EA (23 ± 1 yr) on oral contraceptives (EA-OC). Multiple indexes of autonomic cardiovascular regulation were assessed: respiratory sinus arrhythmia (RSA), cardiovagal baroreflex sensitivity (BRS) via phase IV and phase II of the Valsalva maneuver, a spontaneous index of BRS, and the heart rate and blood pressure responses to orthostatic stress (20-min 60° head-up tilt). RSA was not different among the groups. There were no group differences in the spontaneous index of BRS (AA = 30 ± 6, EA = 24 ± 3, EA-OC = 29 ± 5 ms/mmHg) or in phase II (AA = 8 ± 2, EA = 7 ± 1, EA-OC = 8 ± 1 ms/mmHg) of the Valsalva. There was a difference in BRS during phase IV (AA = 21 ± 3, EA = 15 ± 1, EA-OC = 26 ± 6 ms/mmHg; ANOVA P = 0.04). Tukey's post hoc test indicated that BRS was greater in the EA-OC group compared with the EA group ( P = 0.04). There were no differences in cardiovascular responses to orthostatic stress among the groups. In conclusion, AA do not display signs of impaired autonomic function and orthostatic responses compared with EA or EA-OC during the follicular phase of the menstrual cycle.
Neural Bases of Postural Control
Authors: Deliagina Tatiana G. , Orlovsky Grigori N. , Zelenin Pavel V. , Beloozerova Irina N.
Published: May 2006

The body posture during standing and walking is maintained due to the activity of a closed-loop control system. In the review, we consider different aspects of postural control: its functional organization, the distribution of postural functions in different parts of the central nervous system, and the activity of neuronal networks controlling posture.
The Kindling Fluorescent Protein: A Transient Photoswitchable Marker
Authors: Henderson J. Nathan , Remington S. James
Published: May 2006

Passive fluorescent protein markers are indispensable for dynamic cellular imaging; however, they are unselective, introduce constant background fluorescence, and require continuous observation. Photoactivatable fluorescent proteins have now been developed whose fluorescence can be switched on and off by illumination, allowing selective and direct tracking of tagged objects without the need for continuous imaging. The “kindling fluorescent protein” is a photoactivatable marker with a novel twist: it turns itself off after a selectable period.
Evaluation of Mild Head Injury in a Pediatric Population
Authors: Boran Burak O. , Boran Perran , Barut Nehir , Akgun Cem , Celikoglu Erhan , Bozbuga Mustafa
Published: May 2006

Approximately 5 million children present to emergency departments, seeking care for head injuries, each year, and 80% of these children are classified as cases of mild head injury. Due to the huge number of patients and low frequency of intracranial lesions in this group, obtaining a computed tomography scan for each and every patient is a significant economic problem. This study was conducted to identify the clinical parameters and the radiographic findings that may be associated with intracranial lesions in children with mild head injury. 421 patients, with a Glasgow Coma Scale score of 15 and without any focal neurological deficit, were studied. Intracranial lesion was noted in 37 cases (8.8%). Sensitivity of a plain radiogram was 43.2%, and specificity was 93%. An intracranial pathology was demonstrated in 28.9% of the patients with a linear skull fracture. The only clinical parameters associated with an increase in the frequency of detection of intracranial lesions were posttraumatic seizures and loss of consciousness. Age, sex, headache, vomiting and scalp lacerations were not associated with a higher frequency. Even when patients with a history of loss of consciousness or posttraumatic seizure were subtracted from the study group, intracranial lesions were noted in 4.1% of the cases, and in 1.8% neurosurgical intervention was required. Computed tomography is the gold standard in the evaluation of pediatric patients with mild head trauma, and every child who has experienced a head injury should undergo a cranial computed tomography evaluation, even if he or she appears in perfect health.
Insurance Barriers for Childhood Survivors of Pediatric Brain Tumors: The Case for Neurocognitive Evaluations
Authors: Taylor Lloyd , Simpson Kit , Bushardt Reamer , Reeves Cara , Elkin T. David , Fortson Beverly L. , Boll Thomas , Patel Sunil
Published: May 2006

Objective: The purpose of the present study was to provide empirical evidence of system-based barriers to psychological services for pediatric brain tumor patients when they are medically indicated. Method: Insurance claims data covering 263,866 insured lives during the 1996 fiscal year were pooled from a cross-sectional national sample of adults and their families insured byprivate insurance companies or self-insured firms. Based on inclusion criteria, records for 209 pediatric brain tumor patients aged 18 and under were extracted and analyzed. Claims data including total amount of payments made on behalf of a member, total length of hospital stays, and total number of unique admissions were recorded for all patients, and current procedural terminology (CPT) codes were analyzed to determine frequency of payment for routinely billed psychological procedures. Results were then compared to the frequency of payment for routinely billed psychological procedures for children with other medical conditions. Results: Results indicate that two of the CPT codes commonly associated with neurocognitive evaluations were reimbursed by these third-party payers for pediatric brain tumor patients during the 1996 fiscal year. Additionally, seven of the CPT codes commonly associated with psychological therapy were also reimbursed. Conclusions: The present findings provide empirical evidence of system-based obstacles (i.e., lack of third-party reimbursement) for medically indicated psychological services in pediatric brain tumor patients.
A Case of Type III Cystic Sacrococcygeal Teratoma
Authors: Yoon Soo Han , Park Se-Hyuck
Published: May 2006

We report a rare case of congenital type III cystic teratoma that may be falsely diagnosed as an anterior sacral meningocele. A female newborn baby presented with a long, white-colored 4 × 1 cm coccygeal cyst posterior to the anus. Magnetic resonance imaging (MRI) demonstrated that a 10 × 4 cm elliptical intrapelvic and -abdominal mass anterior to the sacrum and coccyx extended inferiorly to the retrorectal space. We intraoperatively found that the cyst consisted of a mostly thin, white wall, but also with small posterior narrow nodules. We suggest that all cysts in the sacrococcygeal area should be excluded from teratoma carefully, with MRI.
Mycotic Aneurysm
Authors: Ahmad Faiz Uddin , Mahajan Harsh , Mahapatra Ashok Kumar , Suri Ashish
Published: May 2006

Intracranial aneurysms in early childhood are rare. Mycotic aneurysms as a cause of pyrexia of unknown origin has never been reported. We present a 9-month-old immunodeficient boy who had a long history of irregular fever from neonatal period and presented to us with subarachnoid hemorrhage. Investigation revealed a basilar top aneurysm. We present the clinicoradiological profile and discuss the management strategies.
Successful Chemotherapy for Congenital Malignant Gliomas: A Report of Two Cases
Authors: Tamiya Takashi , Takao Soichiro , Ichikawa Tomotsugu , Chayama Kosuke , Date Isao
Published: May 2006

We describe the cases of 2 patients with a congenital malignant glioma that responded to chemotherapy. In the first case, a 2-month-old boy had a conjugate deviation to the right side and nystagmus. A T1-weighted gadolinium-enhanced magnetic resonance image showed a large tumor in his right frontal lobe. The tumor was partially resected, and the histological diagnosis was malignant ganglioglioma. The child then underwent 6 cycles of chemotherapy (mainly carboplatin and etoposide), and the residual tumor shrank. The tumor was then partially resected during a second operation, after which the patient underwent 5 cycles of chemotherapy (a combination of carboplatin, etoposide, vincristine, ifosfamide, cisplatin and cyclophosphamide). The tumor has not recurred in more than 8.5 years. In the second case, a 2-month-old boy had bulging of the anterior fontanel. The T1-weighted gadolinium-enhanced magnetic resonance image showed a large suprasellar tumor. The tumor was partially resected, and the histological diagnosis was anaplastic astrocytoma. The patient underwent 8 cycles of chemotherapy (MCNU, carboplatin and etoposide) and the tumor has not recurred in more than 7.5 years. Our experience indicates that, if surgical removal and chemotherapy are done aggressively for malignant gliomas in neonates and infants, long-term survival is possible.
Third Ventricular Ependymal Cyst Presenting with Acute Hydrocephalus
Authors: Yano Shigetoshi , Kuroda Jun-ichiro , Makino Keishi , Tsuiki Hiromasa , Morioka Motohiro , Kuratsu Jun-ichi
Published: May 2006

Ependymal cysts are generally located in the cerebral parenchyma but rarely found in the third ventricle. A 4-year-old boy presented with headache, vomiting, and upward gaze palsy. His consciousness gradually deteriorated in the course of 6 h. A magnetic resonance imaging study disclosed dilation of the lateral ventricle and a cystic mass in the third ventricle. We performed an endoscopic resection of the cyst wall. The cyst originated on the lateral wall of the third ventricle and obstructed the aqueduct. Histological examination confirmed a diagnosis of ependymal cyst. The patient recovered quickly and his headache and nausea disappeared. Third ventricular ependymal cysts are a rare cause of acute hydrocephalus but an important differential diagnosis. Their neuroendoscopic resection can resolve disturbances in cerebrospinal fluid circulation, is useful for cyst wall removal, and appears to be superior to shunt placement.
Atypical Teratoid-Rhabdoid Tumor Spreading along the Trigeminal Nerve
Authors: Beschorner R. , Mittelbronn M. , Koerbel A. , Ernemann U. , Thal D.R. , Scheel-Walter H.-G. , Meyermann R. , Tatagiba M.
Published: May 2006

We here describe the case of a boy with an atypical teratoid-rhabdoid tumor (ATRT) of the 4th ventricle at 1 year of age and a local tumor recurrence at 19 months of age. Due to brainstem infiltration, only incomplete tumor resection was possible each time. High-dose chemotherapy, stem cell transplantation and irradiation resulted in complete tumor remission on a control MRI. At 8 years of age, another tumor appeared extending from the cerebellopontine angle along the right trigeminal nerve through Meckel’s cave into the cavernous sinus. The trigeminal tumor was not in continuity with the primary ATRT but was located within the field of prior irradiation, neuroradiologically mimicking a schwannoma or a meningioma. The origin of the trigeminal tumor as a late metastasis of the former ATRT or as a less likely irradiation-induced secondary ATRT and the operative approach are discussed.
Effect of Simvastatin on Coronary Lesion Site Remodeling: A Serial Intravascular Ultrasound Study
Authors: Jensen Lisette Okkels , Thayssen Per , Mintz Gary S. , Carlier Stéphane G. , Pedersen Knud Erik , Haghfelt Torben
Published: May 2006

Background: Direct evidence of coronary artery remodeling can be derived only from serial changes in the external elastic membrane (EEM) and plaque area. The aim of the study was to assess the effect of simvastatin on coronary remodeling in serial intravascular ultrasound (IVUS) studies. Methods: In 39 male patients ECG-triggered transducer pullback IVUS was performed at baseline, after 3 months on a lipid-lowering diet (control period), and after another 12 months of simvastatin 40 mg/day. The lesion site was the image slice with maximum plaque burden at 3 months. Results: Absolute changes in the EEM area correlated significantly with changes in plaque area during the control period [B = 0.966, r = 0.792 (95% CI 0.71–1.22); p < 0.001] and during simvastatin treatment [B = 0.945, r = 0.822 (95% CI 0.73–1.16); p < 0.001], but there was no significant difference in the slope (ΔEEM/Δplaque) between the two time intervals. After 12 months of simvastatin, there was a significant reduction in the lesion EEM area of 4.6% (p = 0.006) and in the lesion plaque area of 5.9% (p < 0.001), but there was no change in reference measurements. As a result, the remodeling index was reduced by simvastatin from 1.01 ± 0.12 to 0.95 ± 0.09 (p < 0.001). Conclusion: Simvastatin decreases the remodeling index by reducing lesion, but not reference plaque and EEM area. However, simvastatin does not affect direct evidence of remodeling (ΔEEM/Δplaque) obtained using serial IVUS studies.
An Ongoing Pregnancy after Frozen Thawed Embryo Transfer in a Patient with Klinefelter’s Syndrome
Authors: Yarali Hakan , Bozdag Gurkan
Published: May 2006

Background: Pregnancy following frozen thawed embryo transfer in a patient with nonmosaic Klinefelter’s syndrome is extremely rare. A healthy ongoing pregnancy achieved with frozen thawed embryo transfer in a patient with nonmosaic Klinefelter’s syndrome was described. Method: A case report from a tertiary center for assisted reproductive technologies. A 34-year-old man with azoospermia and nonmosaic Klinefelter’s syndrome and his 26-year-old wife presented with primary infertility of 8 years’ duration. Frozen thawed embryo transfer following intracytoplasmic sperm injection using surgically retrieved spermatozoa was performed. Results: A healthy ongoing pregnancy with a normal 46,XY karyotype was achieved with day 3 frozen thawed embryo transfer. Conclusion: Frozen thawed embryo transfer may be a viable option to achieve pregnancy in patients with Klinefelter’s syndrome.
Accuracy of Conventional plus Transoral Carotid Ultrasonography in Distinguishing Pseudo-Occlusion from Total Occlusion of the Internal Carotid Artery
Authors: Fujimoto Shigeru , Toyoda Kazunori , Kishikawa Kazuhiro , Inoue Tooru , Yasumori Kotaro , Ibayashi Setsuro , Iida Mitsuo , Okada Yasushi
Published: May 2006

Background: To investigate the accuracy of conventional carotid ultrasonography (CCU) combined with transoral carotid ultrasonography (TOCU) for distinguishing pseudo-occlusion from total occlusion of the internal carotid artery (ICA). Methods: This study included 95 patients who were suspected of having an occlusion of the ICA on magnetic resonance angiography (MRA) and underwent both CCU and conventional digital subtraction angiography (DSA) in order to confirm the diagnosis. TOCU was also performed to observe the cervical portion of the ICA distal to the stenosis. We compared the ultrasonographic findings with the DSA findings. Results: Twelve of the 95 patients were defined as having an ICA pseudo-occlusion on DSA. On B-mode images with CCU color Doppler, slight residual flow signals in the ICA lumen were shown in 20 patients. Among them, 2 patients had a pulsed Doppler waveform of the distal ICA occlusion pattern. Among the remaining 18 patients, 4 had a pulsed Doppler waveform of the to and fro flow pattern, and 14 had a weak antegrade flow pattern in the ICA lumen. The conventional ultrasonographic method showed 100% sensitivity with 93% specificity for diagnosing an ICA pseudo-occlusion. The addition of TOCU findings increased the specificity to 98%. In 2 patients, who were overdiagnosed as having an ICA pseudo-occlusion even using TOCU, DSA revealed an occlusion of the ICA distal to the ophthalmic artery with a severe stenosis of the proximal ICA. Conclusions: Using conventional and transoral carotid ultrasonography, an ICA pseudo-occlusion can be diagnosed with higher accuracy.
Changes in Brain Volume 2 Years after Extracranial-Intracranial Bypass Surgery: A Preliminary Subanalysis of the Japanese EC-IC Trial
Authors: Jinnouchi Juro , Toyoda Kazunori , Inoue Tooru , Fujimoto Shigeru , Gotoh Seiji , Yasumori Kotaro , Ibayashi Setsuro , Iida Mitsuo , Okada Yasushi
Published: May 2006

Background and Methods: We studied changes in brain volume on magnetic resonance imaging in 10 patients with and without extracranial-intracranial (EC-IC) bypass surgery who met the inclusion criteria for the Japanese EC-IC Bypass Trial, a multicenter, randomized, prospective study of patients with hemodynamic brain ischemia due to cerebral artery occlusive disease. We also examined the association of cerebral hemodynamics on single-photon emission computed tomography with the changes in brain volume. Results: The affected/unaffected ratio of the percent brain volume declined in patients without EC-IC bypass surgery (p < 0.02, n = 4), and the affected/unaffected percent regional cerebral blood flow ratio increased in patients with the surgery (p < 0.03, n = 6). Acetazolamide reactivity increased in the affected hemisphere of patients with surgery (p < 0.01). Two-year increase (decrease) in acetazolamide reactivity of the affected hemisphere showed a significant positive correlation with 2-year changes in the affected/unaffected percent brain volume ratio (R2 = 0.737, p = 0.0007). Conclusions: Change in acetazolamide reactivity might be a good predictor for brain atrophy in cerebral artery occlusive disease.
Early Mobilisation after Stroke: Review of the Literature
Authors: Diserens Karin , Michel Patrick , Bogousslavsky Julien
Published: May 2006

Background: Mobilisation of acute stroke patients – in bed and out of bed as early as possible – is currently recommended to prevent general and neurological complications. However, mobilisation protocols are poorly defined and need to be standardised in order to evaluate their clinical benefits. The purpose of this study is to highlight recent advances in recommendations for mobilisation of acute stroke and early neurological rehabilitation as found in the recent literature. Methods: A Medline research was conducted from January 1950 to August 2005. Results: Data synthesis of the observational studies and meta-analyses suggests that for most patients with acute stroke, early mobilisation is not harmful and may well be beneficial. However, no controlled study exists comparing early (e.g. 1–3 days) versus late (e.g. 1–2 weeks) mobilisation. Based on the available data and on pathophysiological considerations, we have developed a partially individualised procedure with precise entry and exit points for early mobilisation according to clinical status. Conclusions: Insufficient data are available to prove the beneficial effects of early mobilisation after stroke, although early neurological rehabilitation as part of routine stroke unit care seems to contribute to good long-term outcome. This article presents a standardised procedure for early mobilisation that may be tested in a randomised study between early mobilisation out of bed (3 days) compared to late mobilisation (6 days).
A Two-Base Deletion –439delGC in the Melanocortin-4 Receptor Promoter Associated with Early-Onset Obesity
Authors: Valli-Jaakola Kaisa , Palvimo Jorma J. , Lipsanen-Nyman Marita , Salomaa Veikko , Peltonen Leena , Kontula Kimmo , Schalin-Jäntti Camilla
Published: May 2006

Background/Aims: Mutations in melanocortin-4 receptor (MC4R) are the most common genetic cause of human obesity. Mutations in MC4R promoter could also underlie obesity, but have so far not been reported. Transcription factor nescient helix-loop-helix 2 (Nhlh2) is a novel obesity candidate gene. We searched for mutations in MC4R promoter and Nhlh2 gene in 152 children with severe early-onset obesity. Lean subjects (n = 447) served as controls. Methods: MC4R promoter and Nhlh2 gene were investigated by sequencing. Gel shifts and reporter gene assays were used to investigate a deletion in MC4R promoter. Mutation carriers were carefully characterised. Weight charts from index patients and relatives were analysed. Results: We identified a deletion, –439delGC, in MC4R promoter in 2 severely obese, unrelated children and their family members, but not in controls. Index patients and mutation-carrying relatives were affected by early-onset obesity, while non-carriers had normal childhood weight development. The deletion is located at a potential Nhlh2-binding site and gel shift assays showed that Nhlh2 binds to this site. No significant differences in mutant compared to wild-type MC4R promoter activities were detected. No mutations were identified in Nhlh2 gene. Conclusion: We report an MC4R promoter mutation, –439delGC, associated with early-onset obesity and show that transcription factor Nhlh2 recognises this site in vitro. Nhlh2 mutations unlikely underlie severe human obesity.
Iron Deficiency in Goitrous Schoolchildren of Semirom, Iran
Authors: Siavash Dastjerdi Mansour , Hashemipour Mahin , Rezvanian Hasan , Kazemi Fatemeh , Najafian Alireza , Mohammady Mohammad , Aminorroaya Ashraf , Amini Masoud , Kachuei Ali , Hassan Moaddab Mohammad
Published: May 2006

Background: Iodine deficiency produces the spectrum of iodine deficiency disorders (IDDs): endemic goiter, hypothyroidism, cretinism, and congenital anomalies. Other factors, including goitrogens and micronutrient deficiencies, may influence the prevalence and severity of IDDs and response to iodine supplementation. This cross-sectional, descriptive study was performed in 2003 on elementary school children of Semirom, a mountainous region of Iran, where goiter was hyper-endemic in 1994, but the goiter prevalence had not decreased as expected many years after salt iodization and iodine injection. Some possible risk factors associated with goiter in that area were evaluated, and the results of iron study are presented here. Methods: 1,869 cases were selected by a multistage cluster sampling procedure. Grade 2 goitrous children were compared with equal number of nongoitrous children for serum iron, ferritin, transferrin, thyroxin, TSH and urine iodine concentrations (UIC). Results: 210 children (105 goiter grade 0 and 105 goiter grade 2) entered this sub-study. Of 210 participants, 70 children had low transferrin saturation, 13 had low serum ferritin and 9 children had both problems. There was no significant difference in goiter rate between children with low iron indices and others.There was no significant correlation between serum iron, ferritin or transferrin saturation with other variables including T4, UIC and goiter stage. Conclusion: The present study reveals that in the area studied, iron deficiency cannot explain the high prevalence of goiter, so other responsible factors should be investigated.
Susceptibility of Mycobacterium tuberculosis Strains to Gatifloxacin and Moxifloxacin by Different Methods
Authors: Somasundaram Sulochana , Paramasivan N. Chinnambedu
Published: May 2006

Background: Considering the potentials of gatifloxacin and moxifloxacin in the treatment of tuberculosis, the present study was aimed to define resistance to both these drugs. Methods: Fifty Mycobacterium tuberculosis isolates, consisting of 30 ofloxacin-susceptible and 20 ofloxacin-resistant strains, were tested for their susceptibility to gatifloxacin and moxifloxacin using different susceptibility testing methods, namely the absolute concentration method on Lowenstein-Jensen medium (LJ), the proportion susceptibility testing method (PST) on LJ and 7H11 agar media, and the BACTEC radiometric method. Result: The minimal inhibitory concentration (MIC) of gatifloxacin and moxifloxacin was 1 µg/ml by the absolute concentration method on LJ. In the PST method on LJ and 7H11, using a criterion of ≧1% growth as resistant, there was 100% agreement with the absolute concentration method at a concentration of 0.5 µg/ml for gatifloxacin, and 96% agreement with the BACTEC method at a concentration of 0.25 µg/ml. For moxifloxacin, results by the PST method showed 96% agreement with the absolute concentration method on LJ at a concentration of 1 µg/ml and 92% agreement at a concentration of 0.5 µg/ml for both the absolute concentration method on 7H11 and the BACTEC method. Conclusions: The MICs of gatifloxacin and moxifloxacin were much lower than the MICs of other quinolones like ofloxacin and ciprofloxacin. Additionally, these two drugs have shown a low mean MIC and low concentration as a definition of resistance, which might help in treating the patients with low levels of quinolone resistance.
Role of Oxidative Stress in Remodeling of the Myocardial Microcirculation in Hypertension
Authors: Zhu Xiang-Yang , Daghini Elena , Chade Alejandro R. , Rodriguez-Porcel Martin , Napoli Claudio , Lerman Amir , Lerman Lilach O.
Published: May 2006

Objective—

We tested the hypothesis that in early hypertension (HT), increased oxidative stress leads to myocardial microvascular remodeling.

Methods and Results—

Pigs were studied after a 12-week observation: normal (n=8), untreated renovascular HT (n=8), or HT+chronic antioxidant supplementation (HT+A, n=6). Left ventricular muscle mass (LVMM) and myocardial blood flow (MBF) reserve were determined using electron beam computer tomography (CT), and the spatial density and tortuousity of myocardial microvessels (<500 μm) was then measured in myocardial samples with micro-CT. Myocardial microvascular morphology, oxidative stress, inflammation, and growth factor expression were determined in vitro. HT and HT+A had similarly increased arterial pressure and LVMM, but only HT showed impaired MBF response to adenosine. Compared with normal, HT had increased spatial density of myocardial microvessels, which was preserved in HT+A (111.8±7.8, 166.3±15.7, and 106.4±6.1 vessels per cm
2
, respectively). HT also showed microvascular wall thickening, increased systemic and tissue oxidative stress, inflammation, and expression of vascular endothelial growth factor and its receptor Flk-1, most of which were attenuated by antioxidants.

Conclusions—

Myocardial microvascular remodeling in early HT is accompanied by tissue oxidative stress, inflammation, and altered growth factor expression, and attenuated by antioxidant intervention. This study underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early HT.
Laminar Shear Stress Inhibits Cathepsin L Activity in Endothelial Cells
Authors: Platt Manu O. , Ankeny Randall F. , Jo Hanjoong
Published: May 2006

Objective—The cysteine proteases, cathepsins, have been implicated in vascular remodeling and atherosclerosis, processes known to be regulated by shear stress. It is not known, however, whether shear regulates cathepsins. We examined the hypothesis that shear stress regulates cathepsin activity in endothelial cells.

Methods and Results—Mouse aortic endothelial cells (MAECs) exposed to atheroprotective, unidirectional laminar shear (LS) degraded significantly less BODIPY-labeled elastin and gelatin in comparison to static and proatherogenic oscillatory shear (OS). The cathepsin inhibitor E64 also reduced this activity. Gelatin zymography showed that cathepsin activity of MAECs was blunted by LS exposure and by a cathepsin L inhibitor but not by cathepsin B and S inhibitors, whereas a cathepsin K inhibitor had a minor effect. Cathepsin L siRNA knocked down cathepsin L expression, gelatinase, and elastase activity in OS and static MAECs. A partial reduction of cathepsin B protein raised the possibility that the siRNA effect on the matrix protease activity could have been attributable to cathepsin L or B. Cathepsin B activity study using the synthetic peptide showed it was not regulated by shear.

Conclusions—These results suggest that cathepsin L is a shear-sensitive matrix protease and that it may play an important role in flow-mediated vascular remodeling and atherogenic responses.
Reciprocal and Coordinate Regulation of Serum Amyloid A Versus Apolipoprotein A-I and Paraoxonase-1 by Inflammation in Murine Hepatocytes
Authors: Han Chang Yeop , Chiba Tsuyoshi , Campbell Jean S. , Fausto Nelson , Chaisson Michelle , Orasanu Gabriela , Plutzky Jorge , Chait Alan
Published: May 2006

Objectives—

During inflammation, the serum amyloid A (SAA) content of HDL increases, whereas apolipoprotein A-I (apoA-I) and paraoxonase-1 (PON-1) decrease. It remains unclear whether SAA physically displaces apoA-I or if these changes derive from coordinated but inverse transcriptional regulation of the HDL apolipoprotein genes. Because cytokines stimulate the hepatic expression of inflammatory markers, we investigated their role in regulating SAA, apoA-I, and PON-1 expression.

Methods and Results—

A cytokine mixture (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) simultaneously induced SAA and repressed apoA-I and PON-1 expression levels. These effects were partially inhibited in cells pretreated with either nuclear factor κB (NF-κB) inhibitors (pyrrolidine dithiocarbamate, SN50, and overexpression of super-repressor inhibitor κB) or after exposure to the peroxisome proliferator-activated receptor-α (PPARα) ligands (WY-14643 and fenofibrate). Consistent with these findings, the basal level of SAA was increased, whereas apoA-I and PON-1 decreased in primary hepatocytes from PPARα-deficient mice as compared with wild-type mice. Moreover, neither WY-14643 nor fenofibrate had any effect on SAA, apoA-I, or PON-1 expression in the absence of PPARα.

Conclusion—

These results suggest that cytokines increase the expression of SAA through NF-κB transactivation, while simultaneously decreasing the expression of apoA-I and PON-1 by inhibiting PPARα activation. Inflammation may convert HDL de novo into a more proatherogenic form by coordinate but inverse transcriptional regulation in the liver, rather than by physical displacement of apoA-I by SAA.
Familial Elevated Factor VIII in Children With Symptomatic Venous Thrombosis and Post-Thrombotic Syndrome
Authors: Kreuz Wolfhart , Stoll Monika , Junker Ralf , Heinecke Achim , Schobess Rosemarie , Kurnik Karin , Kelsch Reinhard , Nowak-Göttl Ulrike
Published: May 2006

Objective—

To evaluate the role of factor (F) VIII in children with non-cancer related venous thrombosis (DVT), post-thrombotic syndrome (PTS) or recurrent DVT.

Methods and Results—

FVIII levels were measured in White patients and age- and gender-matched healthy controls. Heritability of factor VIII was estimated in 99 pedigrees by the variance component method implemented in SOLAR. The group of 103 patients showed higher median values of FVIII than 206 controls [FVIII:Ag, 115 versus 96 IU/dL,
P
<0.0001; FVIII:C, 119 versus 106 IU/dL,
P
=0.0009], and had a significantly increased odds ratio (OR) for fibrinogen-adjusted elevated FVIII levels [FVIII >90th percentile versus values below the cut-off: FVIII:Ag, OR 4.3, 95% confidence interval (CI) 1.5 to 12.1; FVIII:C, OR 5.5, CI 2.03 to 15.06]. PTS occurred in 19 of 59 children and persisted in 5 individuals. Recurrent DVT was seen in 8 patients. The heritable(h2)/household(c2) components were calculated for FVIII:Ag levels (h2, 0.48±0.15,
P
=0.0008; c2, 0.21), and FVIII:C (h2, 0.61±0.15,
P
<0.0001; c2, 0.41). When incorporating h2 and c2 in the estimate, the phenotypic variance for FVIII:Ag levels is predominantly explained by h2, whereas c2 stayed significant in the model for FVIII:C (
P
=0.00002).

Conclusions—

Elevated FVIII levels increase the DVT-risk in children.
Pathogenesis of Calcific Aortic Valve Disease
Authors: O’Brien Kevin D.
Published: May 2006

Background—

Over the past 10 to 15 years, calcific aortic valve disease, which includes aortic sclerosis and aortic stenosis, has come to be recognized as an active process, based on: (1) epidemiologic studies demonstrating associations of specific risk factors with increased prevalence or rate of progression of aortic valve disease; (2) identification, in valve lesions, of histopathologic features of chronic inflammation, lipoprotein deposition, renin-angiotensin system components, and molecular mediators of calcification; and (3) identification of cell-signaling pathways and genetic factors that may participate in valve disease pathogenesis. These studies will be reviewed and organized into a proposed global hypothesis for the pathogenesis of calcific aortic valve disease.
Inhibition of Fibroblast Growth Factor Receptor Signaling Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice
Authors: Raj Tina , Kanellakis Peter , Pomilio Giovanna , Jennings Garry , Bobik Alex , Agrotis Alex
Published: May 2006

Objective—

To determine the significance of fibroblast growth factor receptor (FGFR) expression for the development of atherosclerotic lesions in apoE-deficient (apoE
−/−
) mice.

Methods and Results—

ApoE
−/−
mice fed a high-fat diet were administered the FGFR tyrosine kinase inhibitor SU5402 (25 mg/kg/d sc), which inhibited neointima growth by 85%. We measured its effects on lesion size at the aortic sinus, macrophage and smooth muscle cell (SMC) accumulation, the expression of monocyte chemotactic and retention factors, as well as its effects on FGFR expression/phosphorylation. FGFR tyrosine kinase inhibition reduced phosphorylated FGFRs in lesions by 90%, associated with a 65% reduction in lesion size measured using Oil Red O. Macrophages and SMCs within lesions were reduced by 58% and 78%, respectively. Monocyte chemotactic protein-1 (MCP-1) expression was also reduced, as was the expression of hyaluronan synthase, cyclooxygenase-2, CD36, and endothelial monocyte-activating polypeptide-II. Although 3 FGFR types were expressed in lesions, the effects of SU5402 could be attributed largely to inhibition of FGFR-1 phosphorylation.

Conclusions—

Atherosclerotic lesions in apoE
−/−
mice express multiple FGFRs and an active FGF:FGFR-1 signaling system that promotes atherosclerosis development via increased SMC proliferation, and by augmenting macrophage accumulation via increased expression of MCP-1 and factors promoting macrophage retention in lesions.