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PubMed1991

Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy.

BACKGROUND: We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy. METHODS AND RESULTS: Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01). CONCLUSIONS: DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention.

Coronary Angiography↗
PubMed1991

Occlusion of cremaster collateral circulation alters microvascular reactivity.

Surgical preparation of the rat cremaster skeletal muscle for microvascular study usually involves occlusion of the deferential artery and vein which supply a collateral circulation to the tissue. This allows removal of the testis and ductus deferens, and permits direct observation of the cremaster microvasculature. We examined with intravital microscopy the effect of this occlusion on alpha-adrenergic and nonreceptor-mediated (KCl) constriction of large arterioles (1A, 136 microns i.d.) and venules (1V, 193 microns i.d.). The acutely denervated cremaster was suspended in a tissue bath containing propranolol to block beta-adrenergic receptors. alpha 1-adrenergic (norepinephrine (NE) + rauwolscine), alpha 2-adrenergic (NE + prazosin), and KCl (+ phentolamine) concentration-response curves were obtained for bath-added agonists before vs after occlusion of the deferential circulation. Occlusion had no effect on baseline 1A diameter but increased 1V diameter slightly. Arteriolar alpha 1- and alpha 2-adrenergic sensitivities were unaffected by occlusion, but venular sensitivities were reduced by the same amount (approximately fourfold) for both receptor types. Occlusion increased arteriolar sensitivity to KCl but had no effect of venular KCl sensitivity. These data indicate that occlusion of the deferential collateral circulation can produce significant and varied effects on alpha-adrenoceptor and nonreceptor-mediated constriction of cremaster large arteriolar and venular smooth muscle, and underscore the need to avoid collateral occlusion for certain studies of the cremaster microcirculation.

Animals↗
PubMed2002

p53-independent apoptosis is induced by the p19ARF tumor suppressor.

p19(ARF) is a potent tumor suppressor. By inactivating Mdm2, p19(ARF) upregulates p53 activities to induce cell cycle arrest and sensitize cells to apoptosis in the presence of collateral signals. It has also been demonstrated that cell cycle arrest is induced by overexpressed p19(ARF) in p53-deficient mouse embryonic fibroblasts, only in the absence of the Mdm2 gene. Here, we show that apoptosis can be induced without additional apoptosis signals by expression of p19(ARF) using an adenovirus-mediated expression system in p53-intact cell lines as well as p53-deficient cell lines. Also, in primary mouse embryonic fibroblasts (MEFs) lacking p53/ARF, p53-independent apoptosis is induced irrespective of Mdm2 status by expression of p19(ARF). In agreement, p19(ARF)-mediated apoptosis in U2OS cells, but not in Saos2 cells, was attenuated by coexpression of Mdm2. We thus conclude that there is a p53-independent pathway for p19(ARF)-induced apoptosis that is insensitive to inhibition by Mdm2.

Adenoviridae↗
PubMed1985

[Intracoronary electrocardiography during transluminal coronary angioplasty].

To continuously record an intracoronary ECG during the crucial phase of percutaneous transluminal coronary angioplasty, the coronary guide wire was connected to an ECG recorder. In 25 patients the intracoronary ECG was recorded simultaneously with standard leads I, II and III during balloon occlusion of a coronary artery for 30-60 sec. The wire serving as electrode was positioned in the distal third of the coronary artery to be dilated, thus reflecting changes in the pertinent area of the myocardium. This was the left anterior descending coronary artery in 19 patients, the left circumflex coronary artery in 4 patients, and the right coronary artery in 2 patients. Electrocardiographic signs of ischemia were observed in 16 patients (62%). They were present in both the intracoronary ECG and at least 1 of the standard leads I, II or III in 11 patients, in the intracoronary ECG exclusively in 4 patients, and in the standard lead I exclusively in 1 patient. Sensitivity and specificity as an indicator for chest pain during balloon occlusion were 88% and 89% respectively for the intracoronary ECG and 63% and 78% respectively for the standard leads I, II and III. Sensitivity and specificity as an indicator for poor collateralization (coronary wedge pressure less than or equal to 25 mm Hg) were 100% and 69% respectively for the intracoronary ECG, and 60% and 62% respectively for the standard leads, I, II and III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Sonographic evaluation of patients with portal hypertension.

The availability of real-time sonography has facilitated its use in the assessment of patients suspected of portal hypertension. Dilatation of the portal venous system may occur in portal hypertension, and a portal vein diameter greater than 13 mm is indicative of portal hypertension with a sensitivity of about 50%. Sonographic demonstration of lack of caliber variation of the portal system has a sensitivity of about 80%. The presence of venous collaterals can be demonstrated in about 90% of patients suitable for sonography. The coronary gastroesophageal varices can be seen in 90% when they are large sized, and in 65% when they are small sized. Other collaterals such as umbilical vein, duodenal varices, and gastrorenal and splenorenal varices can be detected. Sonography is a valuable screening procedure in the evaluation of portal hypertension and provides valuable information regarding the size and morphology of the liver and spleen, caliber and patency of the portal venous system, and the existence and location of the varices.

Collateral Circulation↗
PubMed2002

Comparison of accuracy and interreader agreement in side-by-side versus independent evaluations of MR imaging of the medial collateral ligament of the elbow.

RATIONALE AND OBJECTIVES: The authors compared independent and side-by-side evaluation of magnetic resonance (MR) images of the medial collateral ligament (MCL) of the elbow, with regard to sensitivity, specificity, and interreader agreement MATERIALS AND METHODS: Six MR imaging sequences were used to image the MCLs in 28 cadaveric specimens, eight with surgically created lesions. Two reading methods were used. For independent evaluation, the images were first evaluated independently and rated on a five-point scale by two musculoskeletal radiologists experienced in interpreting MR images and blinded to the MCL integrity. The images were then reevaluated on the same scale by both readers after at least 2 weeks, with images from all six sequences shown side by side. For each MR sequence and reading method, the sensitivity and specificity were estimated nonparametrically, and differences were tested with the McNemar test. Interreader agreement was assessed with a K statistic, and differences were tested with Z and chi2 tests after adjustment for the dependence structure between correlated K statistics. RESULTS: For all sequences, side-by-side evaluation generally yielded higher specificity than independent evaluation, as well as better agreement between readers. CONCLUSION: Observer performance is superior when multiple MR imaging pulse sequences are reviewed simultaneously rather than independently and separately. Side-by-side review of different MR pulse sequences enabled higher accuracy and lower interreader variability for evaluation of the elbow MCL. These findings have implications for the design of studies to optimize MR imaging protocols by using multiple pulse sequences and multiple readers.

Aged↗
PubMed1997

Transcranial Doppler ultrasound battery reliably identifies severe internal carotid artery stenosis.

BACKGROUND AND PURPOSE: There is a clinical imperative for noninvasive tests for carotid disease that have high sensitivity. Previous studies have shown that transcranial Doppler ultrasound (TCD) can identify intracranial collateral flow patterns and other hemodynamic consequences of carotid occlusion. We hypothesized that a battery of such TCD findings would have a greater sensitivity than any one TCD finding alone and would have clinical utility in identifying carotid disease. METHODS: We determined the prevalence of seven TCD findings in patients with various degrees of carotid stenosis as measured by a blinded observer on 138 cerebral angiograms. We further determined the sensitivity and specificity of any one finding or any single abnormality in the TCD battery (the combination of all seven findings) for identifying severe (> or = 70%) carotid stenosis by angiography. RESULTS: The following four individual TCD findings were associated (P < .001) with > or = 70% carotid stenosis on cerebral angiography: ophthalmic and anterior cerebral artery flow reversal and low middle cerebral artery flow acceleration and pulsatility. The presence of any single abnormality in the TCD battery had a similar association (P < .001) with > or = 70% carotid stenosis. The individual TCD findings had sensitivities of 3% to 83% and specificities of 60% to 100% for identifying > or = 70% carotid stenosis. The TCD battery had a sensitivity of 95% and specificity of 42% for identifying > or = 70% carotid stenosis. CONCLUSIONS: A battery of TCD findings that can be routinely measured reliably identified patients with > or = 70% angiographic internal carotid artery stenosis with high sensitivity.

Carotid Artery, Internal↗
PubMed2001

Low dose dobutamine echocardiography for predicting functional recovery after coronary revascularisation.

OBJECTIVE: To evaluate the effects of chronic coronary occlusion on the accuracy of low dose dobutamine echocardiography in predicting recovery of dysfunctional myocardium after revascularisation. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 53 consecutive patients with >/= 70% stenosis of the left anterior descending coronary artery (LAD) and regional ventricular dysfunction (group 1, non-occluded LAD; group 2, occluded LAD) who underwent dobutamine echocardiography. INTERVENTIONS: 26 patients underwent coronary artery bypass grafting and 27 had percutaneous transluminal coronary angioplasty. MAIN OUTCOME MEASURES: Baseline studies before revascularisation included cross sectional echocardiography at rest and during dobutamine infusion (5-10 microgram), and coronary angiography. The dobutamine study was performed mean (SD) 35 (28) days before revascularisation. Echocardiography at rest was repeated 90 (48) days after revascularisation. RESULTS: Of 296 dysfunctional segments, 63 in group 1 (43%; 63/146) and 69 in group 2 (46%; 69/150) (NS) improved at follow up. Mean (SD) regional wall motion score index decreased from 1.97 (0.48) (95% confidence interval (CI) 1.01 to 2.93) before revascularisation to 1.74 (0.52) (95% CI 0.70 to 2.78) at follow up in group 1 (p = 0.001), and from 2.12 (0.41) (95% CI 1.30 to 2.98) to 1.88 (0.36) (95% CI 1.16 to 2.60) in group 2 (p = 0.0006). In group 1, sensitivity (87% v 52%; p < 0.0001), negative predictive value (88% v 65%; p = 0.001), and accuracy (77% v 64%; p = 0.01) were all significantly higher than in group 2, despite the angiographic evidence of collaterals in patients with occluded vessels. CONCLUSIONS: Dobutamine echocardiography shows reduced sensitivity in predicting recovery of dysfunctional myocardium supplied by totally occluded vessels. Thus caution should be used in selecting such patients for revascularisation on the basis of a viability assessment made in this way.

Angioplasty, Balloon, Coronary↗
PubMed1997

Changes in the flexibility characteristics of the ankle complex due to damage to the lateral collateral ligaments: an in vitro and in vivo study.

This study was part of a long-term effort to develop a reliable diagnostic procedure for ankle ligament injuries. Earlier efforts led to the development and validation of a six-degrees-of-freedom instrumented linkage capable of measuring the flexibility characteristics of the ankle complex in vitro and in vivo. The major goal of the present study was to determine if these flexibility measurements are sufficiently sensitive to detect the presence of damage to the lateral collateral ligaments of the ankle joint both in vitro and in vivo. The in vitro testing was conducted on the legs from six fresh cadavers before and after serial sectioning of the anterior talofibular ligament and the calcaneofibular ligament. The flexibility in inversion-eversion, anterior drawer, and internal-external rotation was measured before and after resection of the ligaments. The in vivo testing was conducted on five patients with unilateral injuries to the ankle ligament. The flexibility evaluation used for in vitro specimens was also performed on both the injured and the intact ankles. For the in vitro testing, the data analysis was based on comparison of flexibility values before and after resection of the ligaments, whereas the data analysis for the in vivo testing was based on comparison of the flexibility of the injured joint with that of the intact contralateral joint. The results of the in vitro study indicated that both an isolated rupture of the anterior talofibular ligament and combined damage of the anterior talofibular and calcaneofibular ligaments produce statistically significant changes in flexibility. Furthermore, the most sensitive parameters to the presence of ligament injuries were found to be early flexibility in anterior drawer, early flexibility in inversion, and the amount of coupling between internal rotation and inversion. These parameters provided a basis for differentiating between an isolated injury to the anterior talofibular ligament and a combined anterior talofibular and calcaneofibular ligament injury. For an isolated anterior talofibular ligament injury, a significant increase in flexibility in anterior drawer was present, whereas the increase in inversion flexibility or in the amount of coupling was insignificant. However, the increases in inversion flexibility and the amount of coupling became significant when both ligaments were involved. The results of the in vivo study indicated that significant changes in flexibility can be detected in patients with lateral ankle injuries. Finally, both the in vitro and in vivo results suggest that development of a reliable diagnostic test for ankle ligament injury based on changes in passive flexibility may be possible.

Adult↗
PubMed1993

Importance of routine T2-weighted or T2*-weighted coronal images in magnetic resonance imaging of the knee.

Magnetic resonance imaging of the knee is most commonly performed with T1-weighting in the coronal plane. This type of imaging is insensitive to meniscocapsular separation and tears of the medial collateral ligament. T2-weighted and T2*-weighted coronal imaging is sensitive to these abnormalities and should be a part of the routine protocol for imaging the knee.

Collateral Ligaments↗
PubMed2005

[Sensitivity and related factors in iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid myocardial scintigraphy to detect stable effort angina pectoris].

OBJECTIVES: This study evaluated the sensitivity and the related factors in iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy to detect stable angina. METHODS: The subjects were 198 patients with stable angina who underwent BMIPP before percutaneous coronary intervention or coronary bypass graft surgery. Patients with unstable angina, myocardial infarction, congestive heart failure, cardiomyopathy and vasospastic angina were excluded. After investigation of the sensitivity of BMIPP, the patients with single-vessel disease without collateral flow were classified into the normal (123)I-BMIPP uptake group (normal group)or decreased (123)I-BMIPP uptake group (decreased group), and various factors were compared between the two groups. RESULTS: Sensitivity was 61% overall, 58% in single-vessel disease, 69% in double-vessel disease, 53% in triple-vessel disease, 43% in only left main vessel disease, and 89% in left main and other vessel disease (NS). In single-vessel disease, the sensitivity was 40% in 75% coronary artery stenosis, 58% in 90% stenosis, 89% in 99% stenosis, and 69% in total occlusion (p = 0.003). Comparing the deoreased and normal groups, diabetes mellitus was more frequent in the normal group (14.6% vs 39.5%), minimal lumen diameter was smaller (0.75 +/- 0.37 vs 0.98 +/- 0.49 mm) and lesion length was longer in the decreased group (15.4 +/- 4.9 vs 11.6 +/- 5.5 mm). Logistic multivariate analysis showed that the independent factors were diabetes mellitus [odds ratio 0.20, 95% confidence interval (CI) 0.04-0.87, p = 0.03], minimal lumen diameter (odds ratio 0.10, 95% CI 0.02-0.48, p = 0.003) and lesion length (odds ratio 1.12, 95% CI 1.00-1.25, p = 0.03). CONCLUSIONS: BMIPP is useful in stable angina patients because of the acceptable sensitivity. Diabetes mellitus, minimal lumen diameter and lesion length were independent factors associated with decreased BMIPP uptake.

Aged↗
PubMed1990

[Non-invasive evaluation of the greater and collateral circulation in arterial occlusive diseases of the lower extremities].

A method of dosed compressive loads with a simultaneous registration of linear blood flow rate in the femoral artery was used in 32 healthy people and 30 patients with different localization of atherosclerotic process in major vessels with the help of an ultrasound apparatus of Bi-Doppler class and specific blood filling of lower extremities by the method of tetrapolar rheography. It was shown that most sensitive and objective index for the assessment of major and collateral blood circulation is a decrease or absence of the retrograde blood flow.

Aorta, Abdominal↗
PubMed2006

Collateral sprouting of human epidermal nerve fibers following intracutaneous axotomy.

Despite the clinical need, there are no therapeutic compounds available to promote peripheral nerve regeneration. In part, this may be due to a lack of sensitive measures of nerve growth. Here, we describe a novel approach of measuring collateral sprouting of epidermal nerve fibers (ENF) in human subjects and describe the effect of the neuroimmunophilin ligand timcodar dimesylate on collateral nerve sprouting. The objective of this study was to describe a model of intracutaneous axotomy and evaluate the ability of timcodar dimesylate to accelerate human cutaneous nerve regeneration through collateral sprouting. Subjects were randomized to receive placebo, 12.5 or 50 mg/day timcodar dimesylate in a prospective, two-center, double-blind, placebo-controlled trial. A 3-mm distal thigh punch skin biopsy was performed at baseline, and a 4-mm overlapping concentric biopsy was taken after 56 days of treatment. Biopsies were processed to visualize ENF, and the collateral sprouting distance (CSD) was measured. Sixty-two subjects completed the trial, and the CSD was measurable in 52. The CSD (mean +/- SEM) was 474.5 microm +/- 38.3, 473.4 microm +/- 28.4, and 450.8 microm +/- 26.5 for the placebo, low and high dose groups, respectively (p = 0.84). The baseline ENF density was associated with the CSD (p = 0.02). Collateral sprouting was efficiently measured using an intracutaneous axotomy model and suggests a collateral sprouting rate of 8.5 microm/day in healthy subjects. The model was consistent across treatment groups and had a low coefficient of variation. Timcodar dimesylate treatment was safe over an 8-week period but did not improve collateral sprouting among healthy subjects.

Adult↗
PubMed1996

Increased DT-diaphorase expression and cross-resistance to mitomycin C in a series of cisplatin-resistant human ovarian cancer cell lines.

In a series of ovarian carcinoma cell lines selected in vitro for resistance to cisplatin by continuous exposure to increasing drug concentrations, the level of resistance is proportional to the expression of gamma-glutamylcysteine synthetase (gamma-GCS). To determine if other detoxicating genes are coordinately expressed, we measured the activity of DT-diaphorase and cytochrome P450 reductase. The specific activity of DT-diaphorase, but not that of cytochrome P450 reductase, increased with increasing resistance to cisplatin. Steady-state mRNA levels for DT-diaphorase correlated with enzyme activity and hence with cisplatin resistance. Since the activity of DT-diaphorase has been associated with sensitivity to quinones, we studied the cytotoxicity of mitomycin C under oxic conditions. Unexpectedly, resistance to mitomycin C increased proportionally with that to cisplatin (r = 0.997). Pretreatment with buthionine sulfoximine, which inhibits glutathione (GSH) synthesis, failed to sensitize either the sensitive or the resistant lines to mitomycin C. Thus, the basis for collateral resistance to mitomycin C in the cisplatin-resistant lines under oxic conditions is unrelated to overproduction of GSH. Under hypoxia, the toxicity of mitomycin C to the most sensitive (A2780) cell line was unchanged. However, the most resistant (C200) line was 2-fold more resistant to mitomycin C under hypoxic conditions. The coordinate overexpression of DT-diaphorase and gamma-GCS in the resistant cell lines is thus associated with hypoxic cell resistance, and supports the involvement of shared mechanisms of gene regulation in the observed resistant phenotype.

Antineoplastic Agents↗
PubMed1994

Dipyridamole angina: a specific symptom of severe multivessel disease.

BACKGROUND: Several studies have indicated that ischemia induced by dipyridamole is frequently associated with angina or ischemic ST-segment depression and that it occurs mainly in patients with three-vessel disease, those with collateral vessels, or those with both. METHODS: In order to analyze the diagnostic relationships among them, we studied 227 consecutive patients who underwent coronary angiography and dipyridamole-thallium scintigraphy. RESULTS: A perfusion defect was found in 134 patients. Of these, 88 patients (66%) showed no significant ECG modifications or angina; 46 (34%) had a transient ST-segment depression, which was associated with typical angina ('dipyridamole angina') in 12. These 12 patients had three-vessel disease with intercoronary collateral circulation. Among the 134 patients with coronary critical stenoses and a positive thallium-dipyridamole test, collateral vessels were detected in 91 (68%). CONCLUSION: Dipyridamole angina, occurring during a positive dipyridamole-thallium test, is usually a manifestation of severe coronary stenoses with collateral circulation. However, as a diagnostic symptom it is characterized by high specificity but low sensitivity.

Aged↗
PubMed1976

Synaptic organization and acetylcholine sensitivity of multiply innervated autonomic ganglion cells.

The principal cells of the mudpuppy cardiac ganglion receive synapses from three sources: vagal axons, interneurons and axon collaterals from other principal cells. The simplicity of the structural organization and the visual clarity in the living preparation provide favorable conditions for examining the function of these synapses and how different classes of synapses on the same cell influence its function. We have studied the sensitivity of the principal cells to iontophoretically applied acetylcholine--the transmitter at synapses made by the vagal axons and by postganglionic axon collaterals from other principal cells. In normal ganglia, the ACh sensitivity on the cell surface is highest at the region of synapses. Partial denervation, produced by severing the vagus nerves, results in an increased ACh sensitivity in nonsynaptic areas but does not appear to affect synaptic transmission at the remaining synapses.

Acetylcholine↗
PubMed1994

Chronic ankle instability: evaluation with MR arthrography, MR imaging, and stress radiography.

PURPOSE: To compare the efficacy of conventional magnetic resonance (MR) imaging, MR arthrography, and stress radiography in the detection of lateral collateral ligament abnormalities in patients with chronic ankle instability. MATERIALS AND METHODS: Seventeen patients with chronic lateral ankle instability underwent stress radiography, MR imaging, and MR arthrography after intraarticular injection of gadopentetate dimeglumine. Imaging findings were correlated with surgical findings. RESULTS: The anterior talofibular (ATF) ligament was torn in 14 patients, and the calcaneofibular (CF) ligament was torn in 10. MR arthrography was more accurate and sensitive in the detection of ATF tears than was MR imaging or stress radiography (P < or = .05). Associated injuries were detected with both MR imaging and MR arthrography. CONCLUSION: MR arthrography is a sensitive technique for detecting and staging tears of the lateral collateral ligaments.

Adult↗