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Biomedical subjects

D Georgiadis

Publications and source records attributed to D Georgiadis.

At least 55 records · Page 3Linked to original sources

Doppler microembolic signals in patients with two different types of bileaflet valves.

OBJECTIVES: This study was performed to evaluate the prevalence and counts of Doppler microembolic signals in patients with St Jude Medical valves (St Jude Medical, Inc, St Paul, Minn) and patients with ATS valves (ATS Medical, Inc, Minneapolis, Minn) and their relation to clinical parameters. METHODS: A total of 179 outpatients of the department of cardiothoracic surgery were examined. They included 98 men and 81 women, aged 61 +/- 11 years, with ATS (n = 91) or St Jude Medical (n = 88) valves in the aortic (n = 110), mitral (n = 39), or both positions (n = 30). Neurologic examination was followed by transcranial Doppler monitoring for microembolic signals. Monitoring was performed bilaterally over the middle cerebral arteries for 1 hour per session. RESULTS: Microembolic signal counts and prevalence were significantly higher in patients with St Jude Medical as compared with ATS valves. Valve type and presence of diabetes mellitus were the only predictors of microembolic signal prevalence on multivariate analysis. No influence of microembolic signals on cerebral embolic complications was established. Additionally, patients with a postoperative history of cerebral embolic complications did not have a higher number of microembolic signals than remaining patients. Interobserver variability was satisfactory. CONCLUSIONS: Patients with St Jude Medical valves were shown to have significantly higher microembolic signal counts than patients with ATS valves. However, our results suggest that microembolic signal counts cannot be used to predict cerebral embolic complications. Their relation to neuropsychologic deficits remains to be evaluated.

Aged↗

Microembolic signal counts increase during hyperbaric exposure in patients with prosthetic heart valves.

BACKGROUND: Patients with prosthetic heart valves have an increased risk of thromboembolic events, and transcranial Doppler sonography reveals microembolic signals. Whereas microembolic signals were initially assumed to be of particulate matter, recent studies suggest that they are partially gaseous in origin. If this is true, alteration of environmental pressure should change microembolic signal counts. We undertook this study to evaluate the influence of hyperbaric exposure on microembolic signal counts in persons with prosthetic heart valves. METHODS AND RESULTS: Microembolic signal counts were monitored by transcranial Doppler sonography of both middle cerebral arteries under normobaria (normobaria 1), 2 subsequent periods of hyperbaria (2.5 and 1.75 bar), and a second period of normobaria (normobaria 2) in 15 patients with prosthetic heart valves. Each monitoring period lasted 30 minutes. Compression and decompression rates were 0.1 bar/min. Microembolic signal counts increased from 20 (12-78) at normobaria 1 to 79 (30-165) at 2.5 bar (P <.01 vs normobaria 1 and 2), decreased to 44 (18-128) at 1.75 bar (P <.01 vs normobaria 1 and 2.5 bar; P <.001 vs normobaria 2), and returned to 20 (8-96) at normobaria 2 (values are medians and 95% confidence intervals). CONCLUSIONS: Our results strongly suggest that gaseous bubbles are underlying material for part of the microembolic signals detected in patients with prosthetic heart valves.

Aortic Valve↗

Feasibility and safety of moderate hypothermia after massive hemispheric infarction.

BACKGROUND AND PURPOSE: Moderate hypothermia decreases ischemic damage in experimental stroke models. This multicenter study was performed to evaluate (1) the safety and feasibility of moderate hypothermia and (2) its potential to reduce intracranial hypertension in acute stroke patients. METHODS: Fifty prospective patients with cerebral infarction involving at least the complete middle cerebral artery territory treated with moderate hypothermia were evaluated. Hypothermia was induced with the use of cooling blankets as well as alcohol and ice bags within 22+/-9 hours after stroke onset and maintained for 24 to 72 hours; subsequently, patients passively rewarmed over a mean duration of 17 hours. Outcome was assessed at 4 weeks and at 3 months. RESULTS: Time required for cooling to <33 degrees C varied from 3.5 to 11 hours. The most frequent complications of hypothermic therapy were thrombocytopenia (70%), bradycardia (62%), and pneumonia (48%). Four patients (8%) died during hypothermia as a result of severe coagulopathy, cardiac failure, or uncontrollable intracranial hypertension. An additional 15 patients (30%) died during or after rewarming because of rebound increase in intracranial pressure (ICP) and fatal herniation. A shorter (<16 hours) rewarming period was associated with a more pronounced rise of ICP. Elevated ICP values were significantly reduced under hypothermia. Neurological outcome according to the National Institutes of Health Stroke Scale score 4 weeks after stroke was 29, and Rankin Scale score 3 months after stroke was 2.9. CONCLUSIONS: Moderate hypothermia is feasible in patients with acute stroke, although it is associated with several side effects. Most deaths occur during rewarming as a result of excessive ICP rise. Our preliminary observation that a longer duration of the rewarming period limits the ICP increase remains to be confirmed in future studies.

Acute Disease↗

Influence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke.

BACKGROUND AND PURPOSE: We undertook this study to evaluate the influence of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with acute stroke. METHODS: A total of 20 ventilated patients of a neurological intensive care unit were examined under a protocol entailing variation of PEEP to 4, 8, 12, and 4 mm Hg; mean arterial blood pressure (MAP), ICP, heart rate, and mean velocity of the middle cerebral arteries (V(m) MCA) were recorded. RESULTS: CPP significantly changed depending on the various PEEP levels. No significant differences in remaining parameters were evident. Three distinct reaction patterns of the parameters monitored were observed: (1) All parameters remained stable through the various PEEP levels (15 patients, 40 examinations). (2) Increase in PEEP resulted in a significant decrease of MAP, while V(m) MCA remained unchanged, indicating an intact cerebral autoregulation. A slight (statistically insignificant) increase in ICP, which was significantly related to the MAP changes, was evident (7 patients, 16 examinations). (3) Increase in PEEP resulted in a decrease of MAP and V(m) MCA; ICP remained unchanged or demonstrated a slight decline (3 patients, 6 examinations). CONCLUSIONS: PEEP increase up to 12 mm Hg does not significantly influence ICP. The observed marked changes in CPP are mediated through the MAP. Thus, PEEP application should be safe, provided that MAP is maintained.

Adult↗

Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach.

BACKGROUND AND PURPOSE: We undertook this study to evaluate the feasibility of inducing and maintaining moderate hypothermia with the use of endovascular rather than surface cooling. METHODS: Six patients with severe acute ischemic stroke were treated with moderate hypothermia. This was induced and maintained by circulating temperature-adjusted normal saline in a closed-loop system entailing 3 balloons located near the tip of a central line, which dwelled in the inferior vena cava. RESULTS: The mean+/-SD initial temperature of the patients was 37+/-1 degrees C (range, 35.5 degrees C to 38.4 degrees C). The pace of cooling was 1.4+/-0.6 degrees C/h, and target temperature was reached after 3+/-1 hours (range, 2 to 4.5 hours). During hypothermia, the maximal temperature observed was 33.4 degrees C, and the minimal temperature was 32.2 degrees C. Temperature deviations >0.2 degrees C or >0.3 degrees C were observed during 21% or 10% of the hours under hypothermia, respectively. Singultus was the only device-related complication encountered. Pulmonary infection, arterial hypotension, bradycardia, arrhythmia, and thrombocytopenia were the most common side effects. CONCLUSIONS: Induction and maintenance of hypothermia with an intravenous cooling device are feasible. The safety of this approach remains to be evaluated.

Acute Disease↗

Potent and selective inhibition of zinc aminopeptidase A (EC 3.4.11.7, APA) by glutamyl aminophosphinic peptides: importance of glutamyl aminophosphinic residue in the P1 position.

Through the development of a new chemical strategy, aminophosphinic peptides containing a pseudoglutamyl residue (Glu Psi(PO2-CH2)Leu-Xaa) in the N-terminal position were synthesized and evaluated as inhibitors of aminopeptidase A (APA). The most potent inhibitor developed in this study, Glu Psi(PO2-CH2)Leu-Ala, displayed a Ki value of 0.8 nM for APA, but was much less effective in blocking aminopeptidase N (APN) (Ki = 31 microM). The critical role of the glutamyl residue in this phosphinic peptide, both in potency and selectivity, is exemplified by the P1 position analogue, Ala Psi(PO2-CH2)Leu-Ala, which exhibited a Ki value of 0.9 microM toward APA but behaved as a rather potent inhibitor of APN (Ki = 25 nM). Glu Psi(PO2-CH2)Leu-Xaa peptides are poor inhibitors of angiotensin converting enzyme (Ki values higher than 1 microM). Depending on the nature of the Xaa residue, the potency of these phosphinic peptides toward neutral endopeptidase 24-11 varied from 50 nM to 3 microM. In view of the in vivo role of APA in the formation of brain angiotensin III, one of the main effector peptides of the renin angiotensin system in the central nervous system, highly potent and selective inhibitors of APA may find important therapeutic applications soon.

Aminopeptidases↗

Relation between maximum discharge rates on electromyography and motor unit number estimates.

To improve quantitative assessment of motor unit recruitment by standard concentric needle electromyography (CNEMG), hypothenar muscles of 22 healthy subjects, 18 with denervation, and 10 with a myopathy were studied. Discharge rates of motor units were measured in CNEMG recordings comprising action potentials of, at most, 4 motor units. Motor unit number estimation (MUNE) was done using the manual incremental method. In controls, the upper 95% limit of the discharge rate was 16.2/s. In all subjects, a strong nonlinear correlation between the number of motor units and the maximal discharge rate was found (r = 0.88, P < 0.0001). Increased discharge rates were found in all but one of the paretic muscles with denervation, but in none of the myopathic muscles. Measurement of the discharge rate is a simple and reliable procedure. If the discharge rate is high in a hypothenar muscle, loss of motor units can be inferred. Moreover, the discharge rate value gives an estimate of the number of motor units in that muscle. Thus, we suggest that maximal discharge rate be included in electromyographic reports.

Action Potentials↗

Predictive value of S-100beta and neuron-specific enolase serum levels for adverse neurologic outcome after cardiac surgery.

OBJECTIVES: The aim of this study was to evaluate the time course of S-100beta and neuron-specific enolase serum levels after cardiac surgery and their clinical relevance in predicting postoperative adverse neurologic outcomes; the 2 proteins are only released in peripheral blood in association with nervous system lesions. METHODS: We neurologically assessed 190 consecutive patients undergoing elective cardiac operations for coronary artery bypass (n = 147), valve replacement (n = 29), or both (n = 14), before as well as after the operation. Postoperative outcome was classified as type I (uncomplicated), type II (confusion, agitation, disorientation, or epileptic seizures), or type III (stroke, stupor, or coma). Levels of S-100beta and neuron-specific enolase were evaluated in venous blood samples drawn preoperatively and then daily in the first 5 postoperative days. RESULTS: Levels of S-100beta and neuron-specific enolase differed significantly among the 3 groups (type III > type II > type I) throughout the postoperative period and had a diagnostic specificity and specificity of 89% and 79%, respectively, in identifying patients with type III outcome. S-100beta (but not neuron-specific enolase) levels were identified as significant independent predictors for type II and III outcomes (odds ratio 16.2, P <.0004). The same was true for duration of cardiopulmonary bypass (odds ratio 1.02, P <.006). CONCLUSIONS: Serum levels of S-100beta are reliable markers for adverse neurologic outcomes after cardiac surgery.

Biomarkers↗

Differentiation between true microembolic signals and artefacts using an arbitrary sample volume.

We evaluated a new discrimination technique between microemboli (MES) and artefact signals. Monitoring was performed over the middle cerebral artery (55 mm) and the brain parenchyma (29 mm). Intensity changes were expressed as percent of change compared to the value measured in the proximal depth. The cut-off value providing the highest sensitivity and specificity in the differentiation was evaluated using 250 MES and 250 artefact signals, and subsequently analysed in the first part of the study. Intensity values derived from the distal depth were subsequently evaluated in 10 patients undergoing cardiac surgery and 45 patients with potential arterial or cardioembolic source. Intensity changes of 87% (84%-90%) and -58% (-71%-(-48%)) were measured in the initial 500 signals for MES and artefact signals, respectively. The best intensity cut-off value was calculated at 27%. This value was subsequently applied to a total of 1858 MES and 1958 artefacts, resulting to sensitivity and specificity of 96% and 98%, respectively. The proposed technique provided adequate results, warranting further evaluation.

Artifacts↗

Maternal cerebral hemodynamics in pregnancy-related hypertension. A prospective transcranial Doppler study.

AIM: To compare maternal cerebral hemodynamics, as assessed by transcranial Doppler studies, with the clinical and radiological findings in different types of pregnancy-related hypertension and to determine their pathophysiology. METHODS: A prospective study of 66 consecutive pregnant women with hypertensive disorders (eclampsia, n = 3; pre-eclampsia, n = 41; isolated hemolysis, elevated liver enzymes, and low platelet count (HELLP)-syndrome, n = 12; pre-eclampsia superimposed on chronic hypertension, n = 5; chronic hypertension, n = 5) and 21 women with uncomplicated pregnancies. Mean blood flow velocities (Vmean) were assessed serially by means of transcranial Doppler in all basal arteries and correlated with changes in mean arterial blood pressure (MABP) and the clinical course. RESULTS: Patients with the pre-eclampsia/eclampsia syndrome showed significantly elevated Vmean values as compared to controls. In the course of the illness Vmean over the whole length of all insonated basal arteries rose simultaneously. The three eclamptic patients showed the highest Vmean values (156, 182, 192 cm/s, respectively), of the middle cerebral artery (MCA) while MABP was 135, 135, and 150 mmHg, respectively. In pre-eclamptic patients the maximal Vmean MCA ranged from 80 (67, 93) to 145 (114, 151) cm/s [median (25th, 75th percentile)] depending on the severity of clinical presentation. In patients with isolated HELLP-syndrome changes in Vmean were either mild (5/12 cases) or absent (7/12 cases). CONCLUSIONS: Considerable differences in cerebral hemodynamics were observed in the various types of pregnancy-related hypertensive disorders examined in this study. Our findings in patients with pre-eclampsia/eclampsia syndrome suggest a breakdown of autoregulation with hyperperfusion and vasogenic edema being the most probable pathophysiological mechanism.

Cerebrovascular Circulation↗

Cerebrovascular reactivity is impaired in patients with cardiac failure.

AIMS: We undertook this study to evaluate potential changes in cerebral vasoreactivity in patients with cardiac failure and their consequent dependence upon cardiac functional variables. METHODS AND RESULTS: A total of 50 patients with various degrees of heart failure, 20 age-matched controls and 20 normal controls were examined. Cerebrovascular reactivity was examined with the carbon dioxide technique. Mean flow velocities of both middle cerebral arteries as well as end-tidal carbon dioxide partial pressure were continuously registered. Normal controls were examined on two different occasions, to evaluate the technique's reproducibility. Cerebrovascular reactivity was significantly reduced in all examined patients as compared to controls, and in NYHA IV as compared to NYHA II and III patients. A significant relationship between cerebrovascular reactivity and left ventricular ejection fraction was evident. Reproducibility of the technique was satisfactory. CONCLUSION: Our study provided evidence of significantly reduced cerebrovascular reactivity in patients with cardiac failure, which was significantly related to the NYHA grade and the left ventricular ejection fraction.

Blood Flow Velocity↗

Automated identification of Doppler microembolic signals: comparison of two techniques.

An alternative technique for identification of Doppler microemboli signals (MES), based on intensity measurements in the vessel and in an arbitrary sample volume was recently reported. We evaluated the applicability of this approach as stand alone system, and compared it to the standard bigate method (TCD 8, version 8T). Bilateral TCD monitoring was performed in 11 patients with prosthetic heart valves and 15 patients during elective cardiac surgery, using three sample volumes (29 mm, 50 mm and 55 mm). All data was saved on digital audio tapes and evaluated by two experienced observers. Only signals unanimously identified as MES or artifacts by both observers were evaluated. A total of 6189 MES and 11,241 artifacts were further analysed. Sensitivity and specificity of the bigate approach and the technique utilising the arbitrary sample volume were 90.7%, 91.3% and 88%, 91.9% respectively. Simultaneous monitoring over three sample volumes and combination of the two detection algorithms could potentially provide an adequate stand-alone system for MES detection.

Aged↗

Phosphinic peptide inhibitors as tools in the study of the function of zinc metallopeptidases.

The development of the combinatorial chemistry of phosphinic peptides has led to the discovery of both highly potent and selective inhibitors of various zinc metalloproteinases. Several properties of these compounds are reviewed, supporting the view that this class of inhibitors should represent useful tools for probing several aspects of the function of this broad family of proteases in vivo.

Aminopeptidases↗

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↗