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D Georgiadis

Publications and source records attributed to D Georgiadis.

At least 19 recordsLinked to original sources

Phosphinic pseudo-tripeptides as potent inhibitors of matrix metalloproteinases: a structure-activity study.

Several phosphinic pseudo-tripeptides of general formula R-XaaPsi(PO(2)-CH(2))Xaa'-Yaa'-NH(2) were synthesized and evaluated for their in vitro activities to inhibit stromelysin-3, gelatinases A and B, membrane type-1 matrix metalloproteinase, collagenases 1 and 2, and matrilysin. With the exception of collagenase-1 and matrilysin, phosphinic pseudo-tripeptides behave as highly potent inhibitors of matrix metalloproteinases, provided they contain in P(1)' position an unusual long aryl-alkyl substituent. Study of structure-activity relationships regarding the influence of the R and Xaa' substituents in this series may contribute to the design of inhibitors able to block only a few members of the matrix metalloproteinase family.

Kinetics

Diagnostic yield of a 1-MHz transducer in evaluation of the basal cerebral arteries.

The authors examined the efficacy of a 1-MHz transducer in routine ultrasound monitoring. Fifty outpatients (34 women, 16 men; mean age, 65 +/- 2) with inadequate temporal bone window for examination with 2-MHz transducers were re-examined with a 1-MHz transducer. Additionally, 50 controls (34 men, 16 women; mean age 49 +/- 2) with adequate temporal bone window were examined with both the 1- and 2-MHz transducers. Signal quality was classified as good (GQ), adequate (AQ), or poor (PQ). Finally, 30 normal controls were examined with both transducers under standardized conditions, to evaluate potential differences in velocity measurements. A total of 90 temporal windows were lacking in the 50 patients. Use of the 1-MHz transducer resulted in identification of the middle cerebral artery in 68 cases (76%; PQ, n = 13; AQ, n = 29; GQ, n = 26), the anterior cerebral artery in 51 cases (57%; PQ, n = 23; AQ, n = 17; GQ, n = 11) and the posterior cerebral artery in 46 cases (51%; PQ, n = 12; AQ, n = 21; GQ, n = 13). Examination was feasible with both transducers in the 50 controls, with minimal differences in signal quality between the two transducers. Correlation between velocity values acquired with the 1- and 2-MHz transducers was significant for all vessels examined. Best values were measured for the middle cerebral artery, followed by the anterior cerebral artery and posterior cerebral artery. The authors conclude that the use of the 1-MHz transducer increases the yield of transcranial Doppler sonography.

Aged

Intracranial microembolic signals in patients with artificial heart valves: drowning in numbers.

Five years after the first description of Doppler microembolic signals, both their clinical significance and underlying material remain a matter of debate. It appears certain that MES depend on valve type and position, while their relation to other clinical parameters, including neurological complications, is still unclear. A number of clinical and experimental studies are reviewed, most of which argue towards gaseous embolic material.

Embolism, Air

Further evidence of gaseous embolic material in patients with artificial heart valves.

OBJECTIVE: We undertook this study to evaluate the hypothesis that most microemboli signals in patients with artificial heart valves are gaseous, assuming that microemboli counts in cerebral arteries would progressively decline with increasing distance from the generating heart valve. METHODS: A total of 10 outpatients with CarboMedics (Sulzer Carbomedics Inc., n = 5) and ATS prosthetic heart valves (n = 5) in the aortic (n = 8), mitral (n = 1), or both aortic and mitral positions (n = 1) were recruited. Monitoring was performed simultaneously over the middle and anterior cerebral arteries and the common carotid artery for 30 minutes with the 2 MHZ transducers of a color duplex scanner (common carotid artery) and pulsed-wave Doppler ultrasonography (intracranial arteries). All data were harvested in an eight-channel digital audio tape recorder, and microembolic signal counts were evaluated online by two separate observers. RESULTS: Significantly higher microembolic signal counts were recorded in the common carotid artery (112 [75 to 175]) compared with the middle and anterior cerebral arteries (30 [18 to 36], p < 0.0001). Interobserver variability was satisfactory (k = 0.81). CONCLUSIONS: Our results strongly argue for gaseous underlying embolic material in patients with artificial heart valves because bubbles are bound to implode with time.

Adult

[Hearing loss as the leading symptom in anterior inferior cerebellar artery infarction].

Hearing impairment is a rare but characteristic symptom of vertebrobasilar occlusive disease. Two patients with anterior inferior cerebellar artery (AICA) infarction and hearing loss as presenting complaint, are described. In patient 1 progressive bilateral AICA infarction was caused by occlusion of the basilar artery, verified by transcranial Doppler sonography. Initial dizziness and bilateral hearing loss were followed by ataxia, dysarthria, dysphagia and right facial sensory impairment. Hearing loss improved during the second week, parallel to a temporary partial recanalisation of the basilar artery, but the patient subsequently developed further progressive brain stem symptoms and died. A right-sided AICA-infarction was diagnosed in patient 2. Initial symptoms were right-sided deafness and dizziness. Neurological examination revealed nystagmus, ataxia and involvement of th 5th and 6th cranial nerve. A progressive improvement of hearing loss and total recovery of the other brain stem symptoms was evident. In conclusion every patient with sudden hearing loss should be examined for additional brain stem symptoms since this can be the presenting sign of a life-threatening basilar artery thrombosis.

Aged

Influence of transducer frequency on Doppler microemboli signals in an in vivo model.

The purpose of this study was the comparison between 1 MHz and 2 MHz transducers in the detection of Doppler microembolic signals (MES). Intraoperative monitoring was performed over the arterial tubing of the extracorporal circulation circuit in 10 patients undergoing coronary artery bypass surgery, using a pulsed ultrasound machine (DWL X-4). 1 MHz and 2 MHz probes were mounted to insonate sequential tubing segments and all monitoring sessions saved on digital audio tapes (DAT). MES counts and intensity as detected by each probe were subsequently evaluated. Specific interobserver agreement was assessed using Cohen's kappa-statistic. Time delay in the appearance of MES between the transducers was minimal (0-0.1 msec). A total of 5293 (64%) MES were detected by both probes, 2796 (33.8%) only with the 1 MHz and 181 (2.2%) only with the 2 MHz probe. Significant differences in MES intensity were evident when comparing the 1 MHz to the 2 MHz transducer (16.4 +/- 0.1 and 11 +/- 0.1 dB with the 1 MHz and 2 MHz transducers respectively, p < 0.0001). Specific interobserver agreement was satisfactory (k = 0.78). Use of 1 MHz instead of 2 MHz transducers increases the yield of embolus detection in vitro. Evaluation of the applicability and performance of this transducer in clinical settings is warranted.

Catheters, Indwelling

Cerebral hemodynamics during induced tachycardia in routine electrophysiologic studies: a transcranial Doppler study.

Supraventricular and ventricular tachyarrhythmia are established causes of syncope. We investigated the mean blood flow velocities (Vmean) of the middle cerebral arteries (MCA) during routine cardiac electrophysiologic studies in patients with supraventricular and ventricular tachyarrhythmias in order to evaluate the changes in cerebral hemodynamics associated with pre-syncopal and syncopal states. Thirty-two patients with a history of supraventricular (n = 14) or ventricular (n = 18) tachyarrhythmias were investigated in the nonsedated, post-absorptive state in supine position. Vmean was assessed in both MCAs by means of transcranial Doppler under resting conditions, during atrial and ventricular pacing at constant rates (n = 28) and during induction of tachyarrhythmia (n = 4). Mean arterial blood pressure (MABP) and heart rate were also recorded. Seven patients suffered pre-syncope at a heart rate of 187 +/- 45 bpm (mean +/- SD) with an average drop of 44% in the Vmean MCA, and statistically insignificant changes in MABP. Five patients suffered syncope during tachyarrhythmia (mean heart rate 283 +/- 42 bpm) with a reduction of 69% in the Vmean MCA. MABP could be assessed in two of those patients and showed a drop of 15 and 43 mmHg, respectively. During tachyarrhythmia pre-syncope and syncope are associated with an average reduction in Vmean MCA by 44% and 69%, respectively. The decrease in MCA blood flow velocity is a more important predictive factor for the development of pre-syncope and syncope than the MABP.

Adult

Automated intraoperative detection of Doppler microembolic signals using the bigate approach.

BACKGROUND AND PURPOSE: We undertook this study to evaluate the performance of an automated detection software in the detection of Doppler microembolic signals (MES) during cardiac surgery. METHODS: Intraoperative monitoring was performed over two spatially separated vessel segments of each middle cerebral artery in 18 patients undergoing coronary artery bypass surgery (n= 16) or cardiac valve replacement (n=2). All monitoring sessions were saved on digital audiotape and subsequently played back to the same ultrasound machine, set up to automatically detect MES by evaluating the temporary delay in their appearance between the two segments, in the presence of an experienced examiner. Software sensitivity and specificity in MES detection were then evaluated, with the results of the human observer considered the gold standard. RESULTS: A total of 44,933 high-intensity signals (artifacts and MES) were evaluated. Overall sensitivity and specificity of the software, with the human observer considered the gold standard, were 64% and 78.5%, respectively, ranging from 54% to 96% and from 74% to 90% in individual patients. When the overall results of the software were compared with those of the human observer, kappa was 0.72. CONCLUSIONS: The tested software displayed a satisfactory specificity. Provided that the sensitivity is further improved, it could provide a valuable tool in intraoperative monitoring.

Artifacts

Clinical correlations of Doppler microembolic signals in patients with prosthetic cardiac valves: analysis of 580 cases.

BACKGROUND: The clinical relevance of Doppler microembolic signals (MES) in patients with prosthetic cardiac valves was evaluated by merging and statistically reanalyzing patient data from four research institutions (Departments of Neurology, Universities of Aachen, Halle, and Münster, Germany; Department of Medicine and Therapeutics, University of Glasgow, Scotland, and Department of Cardiothoracic Surgery, Western Infirmary, Glasgow, Scotland). METHODS: Transcranial Doppler monitoring for MES was performed over the middle cerebral arteries for 30 to 60 minutes per patient. Prevalence of neurological complications was evaluated with a standard neurological questionnaire in patients carrying the valve implant longer than 3 months (n=369). RESULTS: Significant differences in MES prevalence and counts were noted among the 580 patients depending on valve type (presented with medians and [95% confidence intervals]): St Jude Medical, n=200, 72%, 4 [3 to 6]; Björk Shiley Monostrut, n=99, 92%, 133 [93 to 181]; Medtronic Hall, n=80, 47%, 1 [2 to 5]; ATS, n=61, 52%, 3 [2 to 5]; Tecna, n=38, 71%, 2 [1 to 4]; Carbomedics, n=37, 81%, 8 [5 to 13]; Carpentier-Edwards supraannular, n=54, 39%, 1 [0 to 3]; Sorin biological, n=11, 9%, 0 [0 to 0]. No relation between MES counts and valve size, international normalized ratio, patients' age, cardiac rhythm, or implant duration was noted. No significant differences in MES counts or prevalence (22 [3 to 68] versus 5 [3 to 6] and 63% versus 69%, both P>.05), in valve duration, valve position, valve type, patients' age, sex, cardiac rhythm, or international normalized ratio were evident between neurologically symptomatic (n=42) and asymptomatic patients. CONCLUSIONS: MES in patients with prosthetic cardiac valves depend on the type and, in certain valve types, the position of the valve implant and possess no direct clinical significance.

Age Factors

Differentiation between intracerebral hemorrhage and ischemic stroke by transcranial color-coded duplex-sonography.

BACKGROUND AND PURPOSE: The differential diagnosis of intracerebral hemorrhage versus ischemic stroke has critical implications for stroke management. Transcranial color-coded duplex sonography (TCCS) has been shown to identify intracerebral hemorrhages and intracerebral vessel occlusions. We conducted this study to evaluate the sensitivity and specificity of TCCS in this differential diagnosis and in the detection of stroke complications. METHODS: One hundred fifty-one patients (58 women, 93 men; mean age, 65.6 years [range, 32 to 89 years] ) with acute hemiparesis were enrolled in this prospective study. On admission all patients had a complete neurological examination. A cranial CT scan and a sonographic examination of the brain parenchyma and all extracranial and intracranial cerebral arteries were conducted. The sonographer was blinded for the radiological findings. RESULTS: According to CT criteria, 60 patients had an intracerebral hemorrhage and 67 patients had an ischemic stroke, and in 24 patients CT findings were inconclusive, showing neither bleeding nor an ischemic stroke. On sonographic examination, 18 patients (12%) had no sufficient acoustic bone window. Of the remaining 133 patients, 126 (95%) were diagnosed correctly by sonography in agreement with CT. Sonography missed 3 atypical bleedings (2 with upper parietal location). In 4 patients without bleeding, an intracerebral hemorrhage was suspected by TCCS because of increased white matter echo density due to microangiopathy. Stroke complications depicted by CT (disturbance of cerebrospinal fluid circulation, hemorrhagic transformation, midline shift, ventricular bleeding) (n=54) were correctly shown by TCCS in 45 patients (83%). No complication was missed that would have required further treatment. CONCLUSIONS: In comparison to the "gold standard" of CT, TCCS identified stroke complications and differentiated between intracerebral hemorrhage and ischemic stroke with reasonable sensitivity. Thus, if CT is not readily available, TCCS may complement clinical examination in patients with acute stroke. In addition, it may also be useful in detecting stroke complications in the follow-up of stroke patients.

Adult

Intracranial microembolic signals during radiofrequency ablation of accessory pathways.

Intracranial microembolic signals, probably caused by gaseous emboli, are readily detectable in patients undergoing radiofrequency ablation in the left side of the heart only. Clinical value of the detected signals could not be equivocably assessed, because only 2 of the patients who were examined (both emboli positive) had transient neurologic symptoms.

Adult

Identification of Doppler microembolic signals with a bigate probe in patients with prosthetic heart valves.

BACKGROUND AND PURPOSE: The applicability of a bigate probe, simultaneously harvesting two spatially separated vessel segments, in the identification of Doppler microembolic signals (MES) was evaluated. METHODS: One hundred and ninety-seven patients with artificial heart valves were bilaterally monitored over two segments of each middle cerebral artery, with a minimal distance of 5 mm between them, using 2 MHz probes. Time delay in the appearance of high intensity transients between the two segments was calculated off-line, using dedicated software, integrated in the Doppler device. RESULTS: Bigate monitoring was feasible in 96% of patients. MES prevalence and counts were 37% and 26 (18-44) respectively. All but 8.8% of the 2932 MES signals recorded appeared in both Doppler channels, with a time delay of 4.4 (4.2-4.7) msec (range between 0 and 34 msec). Time delay in 97% of artifact signals was under 1 msec. Application of 1 msec as low and 20 msec as high cut-off point between MES and artifacts resulted in the correct identification of 97% of artifacts and 89.6% of MES. CONCLUSIONS: The multigate approach is a reliable method for identification of Doppler microembolic signals in patients with prosthetic heart valves. The value of this technique in other patient groups remains to be evaluated.

Aortic Valve

Ophthalmoplegia plus: clinical relevance of magnetic resonance tomogaphy findings.

The diagnostic value of magnetic resonance imaging (MRI) in patients with ophthalmoplegia plus was evaluated. Twenty patients in whom the diagnosis of opthalmoplegia plus was clinically and histochemically established underwent magnetic resonance and electrophysiological studies. Three types of neuroradiological abnormalities were found in 14 patients: (1) cerebral and/or cerebellar atrophy (n = 11), (2) hyperintense lesions of the white matter or pyramidal tract (n = 2), or (3) both (n = 1). The diagnostic yield of MRI was low, since clinically or electrophysiologically manifest lesions were missed in 4 cases and the pathological findings were non-specific, since they are seen in several demyelinating diseases. Our results suggest that MRI provides no additional information in patients with manifest ophthalmoplegia plus. We conclude that clinical presentation and evidence of ragged red fibers are the cornerstones in diagnosis of ophthalmoplegia plus.

Adult

[Transcranial color-coded duplex ultrasound in interventional therapy of cerebral aneurysms. A pilot study].

PURPOSE: To assess the diagnostic potential of transcranial colour-coded duplex sonography in the recognition of residual perfusion of coiled cerebral aneurysms. METHOD: 10 patients (7 female, 3 male) with angiographically verified cerebral aneurysms (basilar artery n = 2, mean size 8.5 mm; supraclinoid internal cerebral artery n = 2, mean size 15.5 mm; posterior communicating artery n = 2, mean size 7 mm; anterior communicating artery n = 2, mean size 4.5 mm) were examined by TCCD using a 2.25 MHz probe immediately following embolisation and 12-24 hours prior to angiographic evaluation. RESULTS: 9 patients had a sufficient temporal bone window. Transtemporal localization of the embolised aneurysms was feasible in 7 of the 9 cases. One partially thrombosed aneurysm of the basilar artery (1 mm) and one completely thrombosed aneurysm of the anterior communicating artery could not be visualised. In 7 cases no discrepancies between TCCD and angiography were evident, since rest, perfusion (n = 6) and complete thrombosis were unanimously diagnosed as such. Mean size of the rest perfused lumina was 4.4 mm (minimum 1.5 mm; maximum 8 mm). Platinum coils appeared as hyperechogenic lesions with an echogenicity comparable to the skull. CONCLUSION: With TCCD residual perfusion of coiled aneurysms was feasible in most cases. The method seems to be specific but not sensitive in the detection of incompletely coiled aneurysms. Limitations are insufficient transtemporal bone windows and inaccessible aneurysm location, especially the anterior communicating artery.

Adult

Influence of oxygen ventilation on Doppler microemboli signals in patients with artificial heart valves.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the influence of inhalation of 100% oxygen on microembolic signal (MES) counts in patients with artificial cardiac valves. METHODS: A total of 134 outpatients were examined. Transcranial Doppler baseline monitoring (45-minute duration) was performed in all patients under resting conditions. The first 30 patients subsequently underwent transcranial Doppler monitoring for at least 20 minutes under noninvasive positive pressure ventilation with 100% oxygen and for an additional 30 minutes under resting conditions. The same protocol was applied to all following patients with a baseline MES count > or = 10, while the examination was discontinued in the remaining patients. RESULTS: Baseline MES counts < 10, which remained unchanged during oxygen inhalation and the subsequent resting period, were observed in 26 of 30 initial patients. A total of 46 patients with MES counts > or = 10 were identified. Oxygen application was feasible in 43 patients. An exponential MES decrease was noted in 42 patients during oxygen inhalation (statistically significant in 38 patients), followed by a subsequent increase in 38 of 43 patients (statistically significant in 25 patients) under resting conditions. CONCLUSIONS: The exponential reduction of MES counts observed in this study corresponds to blood denitrogenation, thus strongly arguing for nitrogen bubbles as underlying embolic material in prosthetic valve carriers.

Adolescent

Intracranial microembolic signals in 500 patients with potential cardiac or carotid embolic source and in normal controls.

BACKGROUND AND PURPOSE: We undertook this study to evaluate the prevalence and clinical correlations of Doppler microembolic signals (MES) in stroke-prone patients. METHODS: Patients with potential cardiac (n = 300) or carotid (n = 100) embolic source and control subjects (n = 100) were monitored with transcranial Doppler sonography for MES. Transthoracic (n = 192) and/or transesophageal (n = 134) echocardiography and carotid studies (continuous-wave Doppler, n = 181; color-coded duplex, n = 47) were performed in all patients with potential native cardioembolic source. Carotid disease was evaluated by means of continuous-wave Doppler (n = 87), color-coded duplex (n = 70), or intra-arterial angiography (n = 24) in patients with potential carotid embolic source. RESULTS: Overall MES prevalence was 23% in patients with potential native cardioembolic source (infective endocarditis [n = 7] 43%, left ventricular aneurysm [n = 38] 34%, intracardiac thrombus [n = 23] 26%, dilative cardiomyopathy [n = 39] 26%, nonvalvular atrial fibrillation [n = 24] 21%, valvular disease [n = 80] 15%), 55% in patients with prosthetic cardiac valves (mechanical [n = 77] 58%, porcine [n = 7] 43%, homografts [n = 5] 20%), 28% in patients with carotid disease (symptomatic [n = 46] 52%, asymptomatic [n = 54] 7%; P < .01), and 5% in control subjects. No relationship between MES counts and patients' age, sex, or actual medication was noted. The sensitivity and specificity of MES detection in identifying patients with potential embolic sources were 31% and 95%, respectively. CONCLUSIONS: Our study confirmed the reported clinical significance of MES in patients with carotid disease and the high specificity of this technique. The demonstrated low sensitivity of MES detection could be due to short monitoring duration or application of antihemostatic treatment. Prospective large-scale studies are needed to determine the definitive value of MES detection as a diagnostic method in patients with potential cardioembolic source.

Adult

Doppler microembolic signals in children with prosthetic cardiac valves.

BACKGROUND AND PURPOSE: The aim of this study was the evaluation of the prevalence and counts of Doppler microembolic signals (MES) in children with prosthetic cardiac valves and their comparison to those obtained in corresponding adult patients. PATIENTS AND METHODS: Nine children and 43 adults with ATS valves implanted in the aortic position were monitored over both middle cerebral arteries with transcranial Doppler ultrasound. MES were identified on-line according to standard criteria. Heart rate and rhythm, valve type, size and duration, patients' height, International Normalized Ratio, and prevalence of neurological complications were obtained from all study participants. RESULTS: MES prevalence and counts were significantly higher in children compared with adult patients (100% versus 25.5% and 58 [18.5 to 115.5] versus 55 [2 to 10.5], median, 95% CI, respectively). No corresponding differences in valve duration of valve implant were evident, but children has heart rates and were significantly smaller compared with adults. A positive correlation between patients' size, heart rate, and MES counts was noted. CONCLUSIONS: MES counts in children with mechanical prosthetic valves are significantly higher compared with those in corresponding adults. We hypothesize that this is due to (1) the shorter distance between aortic valve and middle cerebral artery, since cavitation bubbles have a short life span and are bound to dissolve with time, and (2) the faster heart rate in children, resulting in a higher number of valve closures per minute.

Adolescent