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PubMed1996

Coronary vascular and endothelial reactivity changes in transgenic mice overexpressing atrial natriuretic factor.

Recent advances in genetic methods permit the introduction of random and defined mutations into the mouse germ line, producing novel mouse strains, some of which affect the heart and vasculature. A TTR-ANF transgenic strain of mice, which constitutively expresses a fusion gene consisting of the transthyretin promoter and the ANF structural gene, has been shown to result in a lifelong elevation of plasma atrial natriuretic factor (ANF) and a chronically lowered arterial blood pressure. However, no established method for efficient functional analysis of possible alterations in coronary vascular function in mice has been reported. In the present study, we describe an isolated mouse coronary artery preparation that permits an effective and reproducible evaluation of coronary endothelial and vascular function. Both left main and right coronary arteries (resting luminal diam 70-90 microns) were isolated and pressurized, and changes in luminal diameter were determined by videomicroscopy. The coronary pressure-luminal diameter relationship was not significantly different between TTR-ANF transgenic and nontransgenic littermates. Relaxation of coronaries to 0.1-100 nM ANF was significantly reduced in transgenic [maximum effect (Emax) = 43 +/- 10% (mean +/- SE) of 11 vessels] compared with nontransgenic (Emax = 73 +/- 7%, n = 15) mice. Similarly, the relaxant response to an endothelium-dependent dilator, acetylcholine, but not to endothelium-independent dilators sodium nitroprusside and isoproterenol, was significantly decreased in transgenic (Emax = 46 +/- 10%, n = 12) compared with nontransgenic (Emax = 85 +/- 5%, n = 14) mice. In contrast, the dose-dependent vasoconstriction to endothelin-1, KCl and the thromboxane mimetic U-46619 was not significantly different between the two groups. These results indicate that lifelong ANF elevation in mice is associated with a decreased responsiveness of coronary vasorelaxation to ANF, possibly resulting from receptor downregulation and/or desensitization. Endothelium-dependent relaxation was also significantly depressed in transgenic mouse coronary arteries, but smooth muscle-specific dilation and constriction were not affected. The present findings are consistent with previous studies of TTR-ANF transgenic mice showing that ANF regulates arterial blood pressure and vascular function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts.

PURPOSE: To develop novel orthotopic xenograft models of medulloblastoma in severe combined immunodeficient mice and to evaluate the in vivo antitumor efficacy of valproic acid. EXPERIMENTAL DESIGN: Orthotopic xenografts were developed by injecting 10(3) to 10(5) tumor cells from four medulloblastoma cell lines (D283-MED, DAOY, MHH-MED-1, and MEB-MED-8A) into the right cerebellum of severe combined immunodeficient mice. Animals were then examined for reproducibility of tumorigenicity, cell number-survival time relationship, and histopathologic features. Tumor growth was monitored in vivo by serially sectioning the xenograft brains at 2, 4, 6, and 8 weeks postinjection. Valproic acid treatment, administered at 600 microg/h for 2 weeks via s.c. osmotic minipumps, was initiated 2 weeks after injection of 10(5) medulloblastoma cells, and treated and untreated animals were monitored for differences in survival. Changes in histone acetylation, proliferation, apoptosis, differentiation, and angiogenesis in xenografts were also evaluated. RESULTS: Tumorigenicity was maintained at 100% in D283-MED, DAOY, and MHH-MED-1 cell lines. These cerebellar xenografts displayed histologic features and immunohistochemical profiles (microtubule-associated protein 2, glial fibrillary acidic protein, and vimentin) similar to human medulloblastomas. Animal survival time was inversely correlated with injected tumor cell number. Treatment with valproic acid prolonged survival time in two (D283-MED and MHH-MED-1) of the three models and was associated with induction of histone hyperacetylation, inhibition of proliferation and angiogenesis, and enhancement of apoptosis and differentiation. CONCLUSION: We have developed intracerebellar orthotopic models that closely recapitulated the biological features of human medulloblastomas and characterized their in vivo growth characteristics. Valproic acid treatment of these xenografts showed potent in vivo anti-medulloblastoma activity. These xenograft models should facilitate the understanding of medulloblastoma pathogenesis and future preclinical evaluation of new therapies against medulloblastoma.

Animals↗
PubMedDate not supplied

Ankle instability: evaluation of the lateral ligaments.

Bilateral ankle stress testing was performed on 25 subjects in a device which controlled position of the foot and the amount of force applied during the examination. Both inversion testing in the anteroposterior plane and anterior drawer testing in the lateral plane were performed in the same group of symptom-free patients. The reproducibility of the test was demonstrated. Previous history of injury, left vs. right handedness, side and anthropometric measurements did not affect the test. There was no difference in the inversion test between ankles tested in neutral and plantar flexion. In functionally normal ankles, the range of inversion "talar tilt" was 0 to 18 degrees while the maximum of anterior displacement on drawer testing was 3 mm. The effective stiffness of the anterior talofibular ligament was thus computed as 65 +/- 34 N/m. Anterior drawer testing appears to evaluate lateral ligamentous integrity of the ankle more critically than the talar tilt test.

Adolescent↗
PubMed2002

Kinematic behavior of the ankle following malleolar fracture repair in a high-fidelity cadaver model.

BACKGROUND: Previous studies involving axially loaded ankle cadaver specimens undergoing a passive range of motion after fracture have demonstrated rotatory instability patterns consisting of excessive external rotation during plantar flexion. The present study was designed to expand these studies by using a model in which ankle motion is controlled by physiologically accurate motor forces generated through phasic force-couples attached to the muscle-tendon units. METHODS: Eight right unembalmed cadaver feet were tested in a dynamic gait simulator that reproduces the sagittal kinematics of the tibia while applying physiological muscle forces to the tendons of the major extrinsic muscles of the foot. Six-degrees-of-freedom kinematics of the tibia and talus were measured with use of a VICON motion-analysis system. The experimental conditions included all combinations of lateral and medial injury to reproduce the clinical classifications of ankle fracture. Statistical analysis was performed with repeated-measures analyses of variance. RESULTS: The talus of the intact ankles demonstrated coupled external rotation and inversion relative to the tibia as the ankle plantar flexed. Osteotomy of the fibula, simulating a lateral ankle fracture, slightly but significantly increased external rotation and inversion of the talus (p < 0.001), whereas disruption of either the superficial or the deep deltoid ligament increased talar eversion (p < 0.003) and disruption of the deep deltoid ligament increased internal rotation (p < 0.0001). The aberrant motions were corrected by repair of the injured structure. CONCLUSIONS: The predominant coupled rotation of the talus is external rotation associated with plantar flexion. Following progressive ankle destabilization, talar external rotation and inversion increased. CLINICAL RELEVANCE: The clinical decision-making process regarding the treatment of ankle fractures centers on determination of whether the injury is expected to result in abnormal motion, which is thought to predispose to the development of arthritis. The present study demonstrated a remarkable degree of ankle stability during stance phase even when there was severe disruption of medial and lateral structures. This finding suggests that a main determinant of clinical outcome after ankle fracture may be ankle motion during swing phase, when ankle stability is not augmented by the combination of axial loading and active motor control of motion. If swing-phase motion is abnormal, then the ankle may be in a vulnerable position at the point of heel-strike.

Aged↗
PubMed1999

Age and sex differences in latencies of waves I, III and V in auditory brainstem response of normal hearing subjects.

Latencies of auditory brainstem response are known to be affected by age and sex. We have investigated the effects of age and sex on absolute latencies of waves I, III and V, the interpeaks intervals I-V, I-III and III-V for left and right ears in 67 healthy subjects with normal hearing. We evaluated the reproducibility of the response between ears which showed consistent data. Latency-intensity plots for waves I, III and V were compared among men and women by estimating the regression equations, with no significant difference in the slopes. Regression analysis revealed that latencies of waves I and V were increased with age in men from childhood up to fifties, according to a linear function. However, in women latencies were not dependent on age. The intervals I-V, I-III and III-V were independent on age for both men and women. The latencies of waves III and V and the I-III and I-V intervals were significantly shorter in women than in men in both ears. The findings obtained in the present study show that gender have a stronger effect on latencies of waves III and V, shortening the I-III and I-V intervals in women. Moreover, latencies of waves I and V increase with age in men.

Adolescent↗
PubMed2001

[Rapid recovery after colonic resection. Multimodal rehabilitation by means of Kehlet's method practiced in Vasteras].

UNLABELLED: By using a multimodal rehabilitation program professor Kehlet has shown accelerated recovery after colonic surgery with hospital stay of only two days, irrespective of open or laparoscopic technique. These results have not been confirmed in other studies. The aim of this study was to replace our traditional approach with Kehlet's multimodal regimen and try to reproduce his reported data. METHODS: 22 patients (median age 67 years) underwent right- or leftsided colectomies, 15 open (7 with midline incisions) and 7 laparoscopically. Continuous thoracic epidural, immediate mobilization and oral nutrition were used. Discharge was planned three days after surgery. On the first postoperative day all had oral intake and on the third day patients were mobilized for a median of 9.7 hours and all had resumed defecation. Pain and fatigue scores (VAS) were low. The median post-operative hospital stay was 3.5 (range 3-8) days. Two patients returned with complications. No cardiopulmonary or infectious complications were seen. The multimodal rehabilitation programme resulted in a quick recovery and a hospital stay of three days in most patients after colonic surgery.

Adult↗
PubMedDate not supplied

Acute muscle stretching and shoulder position sense.

CONTEXT: Stretching is common among athletes as a potential method for injury prevention. Stretching-induced changes in the muscle spindle properties are a suggested mechanism, which may imply reduced proprioception after stretching; however, little is known of this association. OBJECTIVE: To evaluate whether acute stretching of the shoulder muscles affects position sense. DESIGN: A crossover design with subjects randomized to 3 groups. SETTING: A university human research laboratory. PATIENTS OR OTHER PARTICIPANTS: Nine male (age = 24 +/- 3 years) and 9 female (age = 21 +/- 2 years) healthy volunteers. INTERVENTION(S): Stretching of shoulder (1) agonists or (2) antagonists or (3) nonstretching control. MAIN OUTCOME MEASURE(S): We determined position sense acuity of the right shoulder before and after the interventions by having subjects attempt to reproduce arm positions of 15 degrees and 30 degrees (shoulder adduction) while starting at 45 degrees to the sagittal plane. The outcome variables were response variability (variable error) and overall accuracy (absolute error). RESULTS: The relative change in variable error (ie, variable error after/variable error before) was not significantly different between the interventions ( P = .38). Similarly, no change in absolute error was found ( P = .76). Furthermore, no differences were noted regarding test sequence or the interaction of intervention x sequence for either variable error ( P = .73 and .53, respectively) or absolute error ( P = .71 and .67, respectively). CONCLUSIONS: We found no effect on shoulder position sense after an acute bout of stretching of either agonist or antagonist shoulder muscles.

Journal Article↗
PubMed1990

[Congenital atresia of the left main coronary artery ostium--a case suffering from ventricular tachycardia].

A case of congenital atresia of the left main coronary ostium suffering from ventricular tachycardia underwent coronary artery bypass operation. The patient was 17 years old boy. When he was 9 years old he visited our department for the purpose of examining cardiac disease. The diagnostic impression was mitral regurgitation. At 16 years old he suddenly complained tachycardia during exercise. He admitted to our hospital and the tachycardia was proved to be ventricular tachycardia. Left ventriculogram demonstrated a small range of akinesis at the left ventricular apex. And coronary cineangiogram revealed atresia of the left main coronary artery. The left coronary artery was perfused with collateral circulations from right coronary artery. Electrophysiological study was performed. The ventricular tachycardia could be reproducibly initiated and terminated by programmed stimulation. The catheter endocardial mapping was also performed. The source of ventricular tachycardia was supposed to be at the left ventricular apex. At 18 years old coronary artery bypass operation was performed. Internal mammary artery graft was placed to the left anterior descending artery and a saphenous vein graft was placed from the ascending aorta to the left circumflex artery. A small size of myocardial infarction was recognized at the left ventricular apex. And epicardial mapping revealed that the source of arrhythmia was the same region as the myocardial infarction was recognized. Endocardial resection or cryoablation was not performed. Post-operative study was performed 8 months after surgery. The graft flow of the internal mammary artery to the left anterior descending artery was not sufficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1997

Interobserver variability in grading lumbar fusions.

Inter- and intraobserver variability in grading lumbar fusion status radiographically was assessed. The objective was to determine the interobserver variability and intraobserver reproducibility in the assessment of two level noninstrumented lumbar fusions. Fifty sets of radiographs with anteroposterior, left and right bending, and flexion-extension lateral views were assessed by six observers of varying experience and background, with fusion status graded. Kappa statistical analysis revealed only fair interobserver agreement in grading lumbar fusion status. Intraobserver reproducibility was higher in more experienced observers. The results indicate only fair reliability in terms of interobserver agreement to grading of lumbar fusion status. Variability in assessing lumbar fusion radiographically may explain some of the variability in fusion rates reported in the literature and poor correlation that can be seen between clinical outcome and radiologic outcome.

Bone Transplantation↗
PubMed1998

Computer-aided automated landmarking of cephalograms.

The computer-aided method presented is able to interpret and measure radiological structures automatically and reproducibly on a large number of randomly selected lateral head films of different film quality. For example the hard and soft tissue expression of the profile is used to discuss method, application and disadvantages. The performance of the system depends on image quality. The algorithm cannot be influenced by opacifications due to metal structure. In 90% of all cases the contours are identified correctly. Even if the image quality is poor, the recognition rate is about 84%. The selected cephalometric landmarks are placed in the right way in 85% of all cases. The constraint mathematical conditions and the high reproducibility improve the quality process of the cephalometric analysis. Recognition rates of 84% to 90% justify even nowadays the routine use of semi-automatic systems in PC-based analysis. With advancing digital radiography and improved computer performance, image interpreting systems will certainly become established.

Cephalometry↗
PubMed1983

Assessment of left ventricular pressure-volume relations using gated radionuclide angiography, echocardiography, and micromanometer pressure recordings. A new method for serial measurements of systolic and diastolic function in man.

This study was designed to validate the use of combined invasive and noninvasive methods in assessing serial pressure-volume relations in man. Ten patients undergoing cardiac catheterization were studied with simultaneous intracardiac micromanometer pressure recordings, gated radionuclide angiography and echocardiography. Systolic and diastolic function were measured at rest, during right atrial pacing rates of 100 and 120 beats/min and after nitroglycerin administration. Right atrial pacing studies (rate of 100 beats/min) were performed in duplicate to determine the reproducibility of the method. At the conclusion of each study, the model was validated with contrast angiography. Good reproducibility was evident when measuring the maximum and average filling and ejection rates, time to peak filling rate, ejection fraction, the modulus of chamber stiffness, the time course of left ventricular relaxation, global average stress and ventricular work indexes using the model described above. These data were not significantly different (p greater than 0.05) from comparable data obtained from contrast angiography. Right atrial pacing and nitroglycerin administration resulted in predictable alterations in the pressure-volume loop and in the systolic and diastolic measurements. The maximum and average filling rates, ejection rates and time to peak filling rate appeared to be heart rate-dependent variables. By combining available invasive and noninvasive methods, accurate pressure-volume relationships can be determined. Because the method we tested provides accurate volumetric and timing measurements for cardiac events and does not alter hemodynamics, it may be useful for obtaining serial assessments of the pressure-volume relationship in man.

Adult↗
PubMed1997

Reproducibility of ultrasonographically determined intima-media thickness is dependent on arterial wall thickness. The Tromsø Study.

BACKGROUND AND PURPOSE: We compared the reproducibility of B-mode ultrasonographic measurements of intima-media thickness (IMT) in various segments of the right carotid artery and examined whether measurement error was associated with IMT or cardiovascular risk factor levels. METHODS: In 1994/1995 a total of 6676 participants in the Tromsø Study underwent ultrasound examination of common carotid artery IMT. Reproducibility of measurements was assessed by inviting 111 participants to a second ultrasound scan within 3 weeks of the first scan. On each occasion the subjects were examined by three sonographers. RESULTS: The mean between-observer absolute differences in IMT in the far wall of the bifurcation and the near and far walls of the common carotid-artery were 0.15, 0.10, and 0.08 mm, respectively. The corresponding within-observer differences were 0.15, 0.10, and 0.06 mm, respectively. Approximately 70% to 80% of total measurement variability was due to differences among sonographers; the rest was attributable to within-reader variability. Measurement error increased significantly with increasing IMT: the increase was more than twofold over the range of measurements. Cardiovascular risk factor levels were not associated with measurement variability when we controlled for IMT. CONCLUSIONS: We conclude that B-mode ultrasound provides reproducible estimates of the IMT in both the near and far walls of the carotid artery. Although measurement error is generally small, it increases proportionally with the level of IMT.

Aged↗
PubMed2003

Human assisted procreation and human rights--the Greek response to the felt necessities of the time.

The new reproductive technologies enable otherwise infertile couples to reproduce noncoitally. Problems arising from the new reproductive techniques refer to the persons entitled to have access thereto, to the methods accepted (such as procreation by means of a surrogate mother), to the storage and donation of gametes and embryos, to donor anonymity etc. Although homologous and heterologous insemination and in vitro fertilisation have been performed in Greece for a long time, legal provisions thereon have been established only recently: Law 3089/2002 on assisted procreation builds the respective legal frame, regulating main aspects in this crucial field of interwoven human rights and social duties.

Female↗
PubMed2001

Test-retest reliability of functional transcranial Doppler ultrasonography.

The present study evaluates the reproducibility of lateralised blood flow velocity (BFV) changes measured with transcranial Doppler (TCD) ultrasonography during various cognitive paradigms. A total of 20 right-handed volunteers were confronted twice with 13 verbal and visuospatial tasks, with a time interval of 23 to 71 days. No statistically significant differences were found between the lateralisation indices (left BFV change minus right BFV change) on the first and second examinations. Lateralisation indices of eight tasks showed a significant test-retest reliability (r = 0.61 to 0.83). The reproducibility of cognitively induced lateralised BFV changes appears to be task-dependent. The possible influence from technical, physiological, and psychological factors is discussed. We conclude that functional neuroimaging studies based on blood flow data should preferably select cognitive paradigms that demonstrated sufficient test-retest reliability.

Adult↗
PubMed1991

Validation of the thermodilution technique for the estimation of the cardiac output in the unsedated calf.

The purpose of this study was to establish a standardized protocol in order to obtain accurate and reproducible cardiac output (CO) measurements by the thermodilution technique in the unsedated calf. In 5 healthy calves, the effect of various temperatures, volumes, rates, means and sites of injection of the thermal indicator were tested for their effect on accuracy and reproducibility of CO measurement by the thermodilution technique, the Fick method being used as the standard technique. Five milliliters of an iced 5% dextrose solution per 100 kg body weight constituted the correct amount of thermal indicator. Manual injection of the indicator bolus and/or injection of this bolus through the proximal lumen of a thermodilution Swan-Ganz catheter gave poor results of CO measurements by the thermodilution technique. On the other hand, results of CO measurements were highly reliable when the bolus injection was performed by an ECG-synchronized injection pump and/or through a right atrial catheter with a larger diameter and a shorter length than the classical Swan-Ganz catheter. It was concluded that an iced 5% solution of dextrose (5 ml/100 kg body weight) injected through a right atrial catheter by an ECG-synchronized pump gives the most accurate and reproducible CO measurements by the thermodilution technique in unsedated calves.

Animals↗
PubMed1988

Total cavopulmonary connection: a logical alternative to atriopulmonary connection for complex Fontan operations. Experimental studies and early clinical experience.

To understand better the contribution of a right atrium in a valveless atriopulmonary connection, we performed some basic hydrodynamic studies. Pulsation of a valveless chamber in a simple continuous flow circuit was found to generate turbulence and thereby to increase resistance to net forward flow. Visualization of flow through cavities and around corners and measurements of energy losses across nonpulsatile cavities, corners, and stenoses indicated the importance of streamlining. These studies suggested ways in which hydrodynamic designs of the Fontan circulation might be improved. In parallel with these in vitro studies, we have developed a modified approach to Fontan reconstruction that entails exclusion of most or all of the right atrium (total cavopulmonary connection). The operation consists of three parts: (1) end-to-side anastomosis of the superior vena cava to the undivided right pulmonary artery; (2) construction of a composite intraatrial tunnel with the use of the posterior wall of the right atrium; and (3) use of a prosthetic patch to channel the inferior vena cava to the enlarged orifice of the transected superior vena cava that is anastomosed to the main pulmonary artery. The operation was performed in 20 patients between March 1987 and March 1988. The diagnoses were double-inlet ventricle (11 patients), hypoplastic systemic or pulmonary ventricle (seven patients), and absent right atrioventricular connection (two patients). There were two early deaths and one late death. None of the deaths was related to the actual procedure but rather to increased pulmonary vascular resistance (two patients) or systemic ventricular failure (one patient). Total cavopulmonary connections have the following advantages: (1) They are technically simple and reproducible in any atrioventricular arrangement and are away from the atrioventricular node; (2) most of the right atrial chamber remains at low pressure, which reduces the risk of early or late arrhythmias; (3) reduction of turbulence prevents energy losses and should minimize the risk of atrial thrombosis; (4) postoperative cardiac catheterization performed in 10 patients confirmed these favorable flow patterns with minimal gradients throughout the connections. These encouraging early results support the continuing use of total cavopulmonary connection, at least for patients with a nonhypertrophied right atrium.

Anastomosis, Surgical↗