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Biomedical subjects

J D Thomas

Publications and source records attributed to J D Thomas.

At least 235 records · Page 13Linked to original sources

NMDA prevents alcohol-induced neuronal cell death of cerebellar granule cells in culture.

Neuronal cell loss is one of the most debilitating effects of alcohol exposure during development of the nervous system. In this study, primary cultures of neuronal cells (cerebellar granule cells) were used to examine mechanisms of alcohol-induced neuronal cell death. Previously, we established that (Pantazis et al., Alcohol Clin Exp Res 17:1014-1021, 1993): (1) alcohol exposure caused neuronal cell death in cultures of cerebellar granule cells and this cell loss was both time-dependent and dose-dependent; and (2) the vulnerability of cerebellar granule cells to alcohol-induced loss changed with the length of time the cells were in culture before initiating alcohol exposure-that is, younger cultures (1 day in vitro) were much more susceptible to alcohol-induced neuronal cell death than older cultures (4 or 7 days in vitro). The primary goal of the present study was to examine the potential role of the NMDA receptor in alcohol-induced death of cerebellar granule cells in culture. Experiments were performed to test the hypothesis that the alcohol-induced death of cerebellar granule cells can be prevented or reduced by NMDA treatment. Our results indicate that stimulation of the NMDA receptor has a neuroprotective effect and can significantly reduce the alcohol-induced neuronal cell death of newly established cerebellar granule cell cultures. This neuroprotective effect of NMDA is blocked by 2-amino-5-phosphonovalerate, a competitive inhibitor of the NMDA receptor, confirming that this neuroprotective effect is mediated via the NMDA receptor. This is the first report that alcohol's neurotoxic effect can be ameliorated by activation of the NMDA receptor.

Animals↗

Flow characteristics of aortic cannulae.

Atheroembolism from the ascending aorta is an emerging cause of noncardiac complications after open heart surgery. We designed a new arterial cannula specifically to reduce the exit force and velocity of blood flow, thereby reducing the "sandblasting" effect of the exiting blood jet. The cannula has a closed tip and an internal cone that diffuses blood flow such that it enters the aorta via multiple side holes. Fluid dynamics of the cannula were tested against five frequently used cannulae: Sarns High-Flow (3M Sarns High-Flow, Ann Arbor, MI, USA), DLP 83024 (DLP Inc., Grand Rapids, MI, USA), RMI ARS 024C (Research Medical Inc. of Research Industries Corp., Midvale, UT, USA), Bard 1966 (C.R. Bard Inc., Haverhill, MA, USA), and Argyle THI (Sherwood Medical Co. Sub American Home Products Corp., St. Louis, MO, USA). All cannulae had an 8.0-mm external diameter. The new cannula demonstrated a similar pressure drop and internal tip diameter as the others. The exit force (newtons) of the Soft Flow cannula was significantly less than the Sarns High-Flow (p < 0.05), DLP (p < 0.001), RMI (p < 0.01), Bard (p < 0.001), and the Argyle (p < 0.001) cannulae. Peak velocity (cm/s) of the Soft Flow cannula was significantly less than the DLP (p < 0.01), RMI (p < 0.01), Bard (p < 0.01), and Argyle (p < 0.001). The cannulae all had similar hemolysis rates. The new arterial cannula produced the lowest exit force and flow velocity with no increase in hemolysis and may help to decrease the incidence of atheroemboli and its sequelae.

Cardiac Surgical Procedures↗

Selection of patients for transesophageal echocardiography after stroke and systemic embolic events. Role of transthoracic echocardiography.

BACKGROUND AND PURPOSE: This study examined whether patients suffering from stroke and other systemic embolic events may be selected for transesophageal echocardiography on the basis of clinical and transthoracic echocardiographic findings. METHODS: We performed transthoracic and transesophageal echocardiography on 824 patients after stroke and other suspected embolic events. Patients were classified into group A if they were in sinus rhythm and had a normal transthoracic echocardiogram. Group B consisted of all other patients. Transesophageal echocardiographic findings of left atrial spontaneous contrast, left atrial thrombus, complex aortic atheroma, and interatrial septal anomalies were correlated with clinical and transthoracic echocardiographic results. RESULTS: Transesophageal echocardiography detected at least one potential source of embolism in 399 patients (49%): spontaneous contrast in 214 patients (26%), left atrial thrombus in 54 (7%), complex atheroma in 111 (13%), and interatrial septal anomalies in 126 (15%). In group A (n = 236), only 3 (1%) had spontaneous contrast, 11 (4.6%) had complex atheroma, and none had left atrial thrombus. In group B (n = 588), 211 patients (36%, P < .001) had spontaneous contrast, 54 (9.2%, P < .001) had atrial thrombus, and 100 (17%, P < .001) had complex atheroma. Interatrial septal anomalies were detected in similar proportions of patients (18% in group A versus 14% in group B). Left atrial spontaneous echo contrast, thrombus, and complex atheroma were significantly more prevalent in older patients, but interatrial septal anomalies were more prevalent in younger patients irrespective of transthoracic echocardiographic findings. Multivariate analysis identified both an abnormal transthoracic echocardiogram and patient age to be independent predictors of transesophageal echocardiographic findings of left atrial spontaneous echo contrast, left atrial thrombus, or complex atheroma. CONCLUSIONS: Transesophageal echocardiography has a low yield for left atrial spontaneous contrast, left atrial thrombus, or complex aortic atheroma in patients with normal transthoracic echocardiogram and sinus rhythm and in younger patients. Interatrial septal anomalies are more prevalent in younger patients. Transthoracic echocardiogram should be performed in patients after stroke or systemic embolic events as a noninvasive screening tool. We recommend transesophageal echocardiogram for patients with abnormal transthoracic echocardiogram and in younger patients when the finding of a patent foramen ovale may contribute to patient management.

Age Factors↗

Multiplane transesophageal echocardiographic evaluation of mitral valve disease.

With the additional ability to rotate the image around the axis of the centerline of the sector, multiplane transesophageal echocardiography (TEE) improves over single or biplane TEE in ease of use and diagnostic accuracy. This article reviews the anatomic, physiological, and topographic considerations that affect the use of multiplane TEE in evaluation of patients with mitral valve disease. The optimum mitral valve examination includes a true "short-axis" view, obtained by a transverse (zero-degree angle) transgastric image orientation with the probe tip flexed anteriorly, and several "long-axis" views, obtained from various rotations of the basilar multiplane TEE image planes. This provides a useful and accurate means to determine the mechanism of mitral regurgitation, which is useful in planning and timing, determining the likelihood, and predicting the surgical techniques that will be required for mitral valve repair. The postcardiopulmonary bypass (postpump) TEE examination in a patient with mitral regurgitation is a second important component of the process of repair, to determine the presence and severity of residual mitral regurgitation, and identify any complications of surgery. Of 1,550 mitral repair operations studied with postpump echocardiography at our hospital since 1987, a total of 105 (7%) have had second pump runs. Multiplane TEE is also useful to pinpoint the exact site of periprosthetic regurgitation around a mitral prosthesis, enabling direct surgical closure in some cases. Understanding special technical features of multiplane TEE is an important component for optimum utilization of this powerful diagnostic modality.

Echocardiography, Transesophageal↗

Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci.

Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule.

Agammaglobulinaemia Tyrosine Kinase↗

Comparison of persistent thallium perfusion defects by quantitative washout analysis with thallium reinjection in patients with coronary artery disease.

Thallium reinjection can improve the detection of severely ischemic viable myocardium in patients with coronary artery disease. However, a disadvantage of this method is that it requires the acquisition of 3 separate sets of images and the administration of an additional dose of the radiotracer. Alternatively, quantitative analysis of the regional myocardial washout of thallium-201 can be easily obtained from the conventional postexercise and redistribution images without additional imaging time or radiation exposure to the patient. To determine whether this method can predict the results of thallium reinjection, this study analyzed thallium-201 images of 31 patients who had persistent perfusion defects in qualitative exercise/delayed redistribution single-photon emission computed tomographic thallium studies and who underwent thallium reinjection. The quantitative mean radioactive counts of each myocardial segment that had a persistent perfusion defect in the initial and delayed redistribution on 4-hour short-axis tomographic slices were measured to derive a delayed/initial ratio, and these values were compared with the results of thallium reinjection. The delayed/initial ratio was 1.06 +/- 0.22 in 39 segments that improved, versus 0.58 +/- 0.18 in 43 segments without improvement after reinjection (p < 0.001). Thirty-eight of the 39 segments that improved had a ratio of > or = 0.75, versus only 3 of the 43 segments that showed no improvement (sensitivity, 98%; specificity, 91%). The correlation between the delayed/initial ratio and reinjection results was equally high at any segment location or severity. It is concluded that quantitative regional thallium washout analysis predicts the results of thallium reinjection in segments with persistent thallium defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Continuous wave Doppler echocardiography for noninvasive assessment of left ventricular dP/dt and relaxation time constant from mitral regurgitant spectra in patients.

OBJECTIVES: We previously demonstrated experimentally that the mitral regurgitant velocity spectrum can be used to estimate left ventricular pressure throughout systole and may provide a new noninvasive method for estimating maximal dP/dt and the relaxation time constant. This study was designed to test this method in patients. BACKGROUND: The maximal first derivative of left ventricular pressure (dP/dt) and the time constant of left ventricular isovolumetric relaxation (tau) are important variables of left ventricular function, but the need for invasive measurement with high fidelity catheters has limited their use in clinical cardiology. METHODS: Twelve patients with mitral regurgitation were studied. The Doppler mitral regurgitant velocity spectrum was recorded simultaneously with micromanometer left ventricular pressure tracings in all patients. The regurgitant velocity profiles were digitized and converted to ventriculoatrial (VA) pressure gradient curves using the simplified Bernoulli equation and differentiated into instantaneous dP/dt. The relaxation time constant (tau) was calculated assuming a zero pressure asymptote from catheter left ventricular pressure decay (tau c) and from the Doppler-derived VA gradient curve with corrections. Two methods were used to correct the Doppler gradient curve to better approximate the left ventricular pressure decay before calculating the relaxation time constant: 1) adding an arbitrary 10 mm Hg (tau 10), and 2) adding the actual mean pulmonary capillary pressure (tau LA). RESULTS: The Doppler-derived maximal positive dP/dt (1,394 +/- 302 mm Hg/s [mean +/- SD]) correlated well (r = 0.91) with the catheter-derived maximal dP/dt (1,449 +/- 307 mm Hg/s). Although the Doppler-derived negative maximal dP/dt differed slightly from catheter measurement (1,014 +/- 289 vs. 1,195 +/- 354 mm Hg/s, p < 0.01), the correlation between Doppler and catheter measurements was similarly good (r = 0.89, p < 0.0001). The correlation between tau 10 and tau c was excellent (r = 0.93, p < 0.01), but the Doppler-derived tau 10 (50.0 +/- 11.0 ms) slightly underestimated the catheter-derived tau c (55.5 +/- 12.8 ms, p < 0.01). This slight underestimation could be corrected by adding the actual pulmonary capillary wedge pressure to the Doppler gradient curve. CONCLUSIONS: Doppler echocardiography provides an accurate and reliable method for estimating left ventricular maximal positive dP/dt, maximal negative dP/dt and the relaxation time constant (tau) in patients with mitral regurgitation.

Adult↗

Left ventricular diastolic dysfunction in lymphocytic myocarditis as assessed by Doppler echocardiography.

Pulsed-wave Doppler echocardiography of left ventricular (LV) inflows was performed in 30 consecutive patients with biopsy-proven lymphocytic myocarditis. There were 21 men and 9 women (mean age 50 +/- 15 years). LV ejection fraction was < or = 30% in 73% of the patients. Sixty-six percent were in New York Heart Association functional class III to IV. Peak early (E) velocity, late (A) velocity, deceleration time and filling pattern were assessed. These values were compared with a control population. E velocity in lymphocytic myocarditis was significantly higher than in control subjects (79 +/- 34 vs 67 +/- 14 cm/s, p = 0.0034). A velocity was lower in patients with myocarditis than in control subjects (38 +/- 20 vs 49 +/- 12 cm/s, p = 0.0001). Correspondingly, the E/A ratio was greater in the myocarditis group (2.5 +/- 1.3 vs 1.5 +/- 0.5, p < 0.0001). In particular, mean deceleration time in patients with myocarditis was significantly lower than that of control subjects (151 +/- 52 vs 194 +/- 30 ms, p < 0.0001). Diastolic filling patterns were abnormal in 29 of 30 patients (97%) with lymphocytic myocarditis, revealing a restrictive pattern in 25, abnormal relaxation in 4 and a normal pattern in 1. Lymphocytic myo-carditis is therefore associated with LV diastolic dysfunction of a predominantly restrictive pattern.

Adult↗

Spatial and temporal variability in the pattern of recovery of ventricular geometry and function after acute occlusion and reperfusion.

Myocardial ischemia and infarction are known to cause changes in both ventricular shape and function. Little is known about the recovery of ventricular geometry after transient myocardial ischemia and its relationship to recovery of function. To examine the pattern of recovery of ventricular geometry following transient coronary artery occlusion and to assess the relationship of this to the return of systolic function, we used echocardiography to study 13 dogs following 15-minute occlusion of the left anterior descending coronary artery. During ischemia, total endocardial surface area (ESA) increased from 32.55 +/- 1.77 to 45.36 +/- 3.18 cm2 (p = 0.001). The most striking increase was at the apex, where circumference increased from 5.04 +/- 0.24 at baseline to 7.86 +/- 0.43 cm at the end of occlusion (p = 0.0001), an increase of 58%. During reperfusion, ventricular geometry rapidly returned toward normal (baseline), with recovery of 80% of the increase in ESA evident by 15 minutes of reperfusion. Recovery of systolic function was substantially slower (p < 0.005 for all periods of observation during the 2 hours of reperfusion). During reperfusion, recovery of ventricular geometry and function was not uniform throughout the ischemic bed. The apex recovered most slowly, with the centroid of the area of abnormal contraction progressively moving along the long axis of the left ventricle toward the apex. There was also a progressive decrease in the radius of the area of dysfunction, from 2.0 +/- 0.15 at end occlusion to 0.13 +/- 0.07 cm at 120 minutes of reperfusion (p = 0.0001). There was no difference in blood flow between the apical and anterior segments during ischemia or reperfusion. Reperfusion favorably reduced the ischemic zone dilation before recovery of active systolic function and geometric recovery thus may be important in determining ultimate functional recovery. In addition, recovery of function proceeded inward towards the center of the ischemic territory and in a wavefront from the base to apex. This heterogeneous and asymmetric recovery suggests that sampling at one point within the ischemic zone may not reflect the true temporal pattern of recovery.

Acute Disease↗

Quantification of tricuspid regurgitation by means of the proximal flow convergence method: a clinical study.

Quantitation of valvular regurgitation remains an important goal in clinical cardiology. It has been described previously that with the use of color Doppler flow mapping, simple measurements of apparent jet size do not correlate closely with quantitative regurgitant indices. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Assuming hemispherical convergence, flow rate Q can be calculated as Q = 2 pi r2va, where va is the aliasing velocity at a distance r from the orifice. For maximal accuracy, previously validated correction factors must be used to account for the flattening effect of the isovelocity contours close to the orifice and for the actual sector angle subtended by the valve leaflets (alpha), to yield a flow rate formula Q = 2 pi r2va.(vp/vp - va).(alpha/180), where vp is the orifice velocity obtained by continuous wave Doppler. In 45 patients (35 in sinus rhythm, 10 with atrial fibrillation) with tricuspid regurgitation, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated using the proximal flow convergence method and were compared with values obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (SV) calculated by the proximal flow convergence method correlated very closely with values obtained by the Doppler two-dimensional method with r = 0.95 (y = 0.94x + 0.99) and delta SV = -0.3 +/- 5.2 cm3. Regurgitant flow rates (Q) calculated by both methods showed a similar correlation: r = 0.96 (y = 0.97x + 45) and delta Q = 1.6 +/- 429 cm3/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effective regurgitant orifice area in tricuspid regurgitation: clinical implementation and follow-up study.

Analysis of the flow-convergence zone proximal to a regurgitant orifice permits the noninvasive, quantitative measurement of clinically useful parameters of valvular insufficiency. However, many indexes such as flow rate reflect not only the size of the regurgitant lesion but are also highly dependent on the hemodynamic loading conditions. The effective regurgitant orifice area (ROA) in contrast is a more fundamental parameter, less dependent on hemodynamics and more reflective of real changes in the geometry of the valve, making it a promising index for serial assessment of patients. In this study, the measurement of regurgitant orifice area by the flow-convergence method was tested in tricuspid regurgitation and then used to monitor patients noninvasively over time. The effective ROA was calculated in 45 patients with tricuspid regurgitation by means of the flow-convergence method and compared with the ROA obtained with pulsed Doppler echocardiographic methods. An excellent correlation was obtained between the two assessments of ROA (r = 0.96, delta ROA = -0.09 +/- 6.5 mm2). ROA also showed an excellent correlation with other indexes of valvular insufficiency such as regurgitant stroke volume (r = 0.89) and regurgitant fraction (r = 0.88). In a subgroup of 22 patients thought to be clinically stable, ROA was calculated serially over a mean follow-up period of 2 months and its variability compared with that of other flow-based parameters obtainable from proximal acceleration. The variation between the two studies in regurgitant stroke volume and regurgitant flow rate was 5% +/- 20.6% and 5.2% +/- 35.7%, respectively. The effective ROA showed significantly less variability at 1.8% +/- 15%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Should all patients undergo transesophageal echocardiography before electrical cardioversion of atrial fibrillation?

The management of anticoagulant therapy in patients with atrial fibrillation undergoing electrical cardioversion remains controversial, largely because of inadequate studies demonstrating risk or benefit, a relatively inconvenient anticoagulation management strategy and the increasing use of transesophageal echocardiography. Recent investigations into the potential mechanisms involved in the development of thrombus and systemic embolism in patients undergoing electrical cardioversion of atrial fibrillation may provide insight into underlying predisposing factors, with subsequent modification of management strategies. Conventional wisdom suggests that preexisting thrombus is responsible for thromboembolic events after cardioversion. However, development of a thrombogenic milieu after cardioversion, particularly in the left atrial appendage, may also be an important predisposing factor. To protect against both potential mechanisms of embolization, these data support therapeutic anticoagulation for all patients with atrial fibrillation of > 2 days in duration from the time of, as well as after cardioversion for a total of 4 weeks, undergoing cardioversion, even in the absence of thrombus on echocardiography. Therefore, the role of transesophageal echocardiography in this setting should be to enable early cardioversion if atrial thrombus is excluded and to identify high risk patients with atrial thrombi so as to postpone cardioversion and avoid the risk of embolization. Ultimately, however, a controlled, randomized and prospective clinical trial will be required to compare conventional management with a transesophageal echocardiography-guided strategy.

Anticoagulants↗

Evaluation of an ammonium ionophore for use in poly(vinyl chloride) membrane ion-selective electrodes: solvent mediator effects.

A macrotetrolide nonactin-based ammonium ionophore (AI) preparation containing 25% nonactin optimized for use in liquid membrane ion-selective electrodes was investigated for its possible use in poly(vinyl chloride) (PVC) matrix membrane-type electrodes. Nine different plasticizing solvent mediators were employed in the ammonium ion-selective membranes with PVC and the AI preparation. Near Nernstian responses were observed in aqueous solution with electrodes fabricated with dioctyl sebacate-, 2-nitrophenyl phenyl ether-, dibutyl sebacate-, trioctyl phosphate-, dioctyl adipate-, dioctyl phenyl phosphonate- and 2-nitrophenyl octyl ether-plasticized membranes. The responses of these electrodes were found to improve in the presence of a background concentration of non-interfering calcium ions.

Chemical Phenomena↗

Relationship of aortic regurgitant velocity slope and pressure half-time to severity of aortic regurgitation under changing haemodynamic conditions.

The slope and pressure half-time of the aortic regurgitant velocity spectrum have been used as non-invasive markers of regurgitant severity. Recent in vitro and theoretical work, however, has suggested a confounding effect of systemic vascular resistance and left ventricular compliance on these parameters. To study this situation in vivo, we have investigated the determinants of the aortic regurgitant velocity profile in an animal model of aortic regurgitation in which the regurgitation was induced surgically and in which the afterload was varied pharmacologically. Specifically, we examined the relationship of slope and pressure half-time of the aortic regurgitant velocity profile to the severity of aortic regurgitation under varying conditions of afterload using multilinear analysis. Slope varied directly with regurgitant orifice area and inversely with systemic vascular resistance and both left ventricular and aortic compliance (all P < 0.001). Pressure half-time related to these variables in the opposite direction. When the regurgitant orifice was variable in size, slope related directly (P < 0.001) and half-time inversely to the severity of the aortic regurgitation (the clinically expected response). In contrast, when the regurgitant orifice area was constant, slope varied inversely (P < 0.001) and half-time varied directly (P < 0.07) with the severity of the aortic regurgitation. Following nitroprusside infusion, slope tended to increase (P = 0.08) and pressure half-time tended to shorten (P = 0.08) despite a significant reduction in the regurgitant fraction (P = 0.009). Similarly, following dopamine infusion, a significant increase in regurgitant fraction (P = 0.01) was associated with a slight fall in aortic regurgitation slope and a lengthening of the half-time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of angle and flow rate upon hemodynamics in distal vascular graft anastomoses: a numerical model study.

Flow in distal end-to-side anastomoses of iliofemoral artery bypass grafts was simulated using a steady flow, three-dimensional numerical model. With the proximal artery occluded, anastomotic angles were varied over 20, 30, 40, 45, 50, 60 and 70 deg while the inlet Reynolds numbers were 100 and 205. Fully developed flow in the graft became somewhat skewed toward the inner wall with increasing angle for both Reynolds numbers. Separated flow regions were seen along the inner arterial wall (toe region) for angles > or = 60 deg at Re = 100 and for angles > or = 45 deg at Re = 205 while a stagnation point existed along the outer arterial wall (floor region) for all cases which moved downstream relative to the toe of the anastomosis with decreasing angles. Normalized shear rates (NSR) along the arterial wall varied widely throughout the anastomotic region with negative values seen in the separation zones and upstream of the stagnation points which increased in magnitude with angle. The NSR increased with distance downstream of the stagnation point and with magnitudes which increased with the angle. Compared with observations from chronic in vivo studies, these results appear to support the hypothesis of greater intimal hyperplasia occurring in regions of low fluid shear.

Anastomosis, Surgical↗