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Biomedical subjects

A Nicolaides

Publications and source records attributed to A Nicolaides.

At least 37 records · Page 2Linked to original sources
PubMed1999

Vascular surgical society of great britain and ireland: transcranial doppler ultrasonography as a predictor of haemodynamically significant carotid stenosis

BACKGROUND: Transcranial Doppler (TCD) ultrasonography can detect evidence of collateral flow across the anterior communicating artery and/or the posterior communicating artery, which occurs when there is significant alteration of 'inflow' to the brain. The aim of the study was to determine the blood flow velocity produced by a carotid stenosis which produces this haemodynamic effect on the cerebral circulation and evokes collateral circulation. METHODS: Forty-eight patients with varying degrees of carotid stenosis (10 per cent to occlusion) who underwent both carotid duplex and TCD examination were reviewed. An ATL HDI 3000 ultrasound system was used for the carotid and TCD studies. The carotid examination recorded peak-systolic velocity (PSV) and end-diastolic velocity (EDV) in the carotid systems bilaterally. TCD recorded Doppler spectra from the bilateral middle cerebral, anterior cerebral, posterior cerebral, intracranial vertebral and basilar arteries. Collateral flow was assessed in two ways: 'intracranial crossover' collateral and 'posterior to anterior' collateral. Each internal carotid artery (ICA), together with the ipsilateral hemisphere, was analysed for the presence or absence of collateral flow. Data were expressed as mean(s.e.m.). RESULTS: The PSV of the group with collateral circulation was 472(14) cm s-1 and that of the group without collateral flow was 164(3) cm s-1 (P < 0.0001, Mann-Whitney test). The respective EDVs were 158(13) and 58(7) cm s-1 (P < 0.0001). CONCLUSION: PSVs and EDVs in the ICA, in conjunction with collateral flow measured by TCD, are indicators of a haemodynamically significant carotid lesion, and provide more information than two-dimensional imaging studies. In the future, parameters set by combining carotid duplex and TCD investigations may represent the 'gold standard' for evaluation of cerebral blood flow.

Journal Article↗
PubMed1999

Grading internal carotid artery stenosis using B-mode ultrasound (in vivo study)

OBJECTIVE: to determine the value of percentage area and diameter reduction in grading ICA stenosis using colour-coded B-mode transverse ultrasonic images. MATERIALS AND METHODS: measurement of the percentage area and diameter reduction of the common carotid, external carotid and internal carotid (at the point of maximum stenosis) were performed, using duplex scanning with colour-flow imaging preoperatively, in 33 patients (six patients were excluded). The duplex measurements were compared to the percentage area and diameter reduction from transverse section of the specimens. Peak systolic (PSV) and end-diastolic velocities (EDV) were measured at the proximal CCA and ICA within the jet of turbulence. A mm scale was placed next to the specimen block, which was captured by video. The area reduction was measured by playing the video and using the same duplex software. RESULTS: linear-regression analysis of the percentage area reduction of the in vivo against the specimen measurements showed a good linear relationship (r=0.9047). The in vivo duplex measurements had 95% confidence interval (CI) of 8% (95% CI of diameter reduction 5%). CONCLUSION: using the gold standard of fixed histological endarterectomy specimen, the results indicate that transverse image obtained with colour B-mode imaging is more appropriate in determining the degree of stenosis.

Blood Flow Velocity↗
PubMed1999

A simple test to monitor oxidative stress.

BACKGROUND: The role of oxygen free radicals is considered important in the development of cardiovascular disease. However, until recently determination of free radicals plasma levels and the effect of antioxidant therapy on these levels has been difficult. The aim of the study was to determine the oxidative stress and the effect of the antioxidant compound AR(D) Stenovit on this stress in normal subjects and patients with intermittent claudication after oral administration for one week. METHODS: A portable, free radicals (FRs) determination system (D-Roms test, Diacron, Grosseto, Italy) was used. This test is based on the ability of transition metals to catalyse in the presence of peroxides with formation of FRs which are trapped by an alchilamine. The alchilamine reacts forming a coloured radical detectable at 505 nm. The reagents utilised are the cromogen (R1, an alchilamine) and a pH 4.8 buffer (R2). Ten microl of hemolysis-free serum are to 1 ml of R2 and to 10 microl of R1. The sample is mixed, incubated (1 min; 37 degrees C) and read for optical density. After another minute, the sample is read again. The average delta A/min is multiplied by a K factor and calculated using serum with defined value. RESULTS: In normal subjects the mean (+/-SD) levels of free radicals were 312+/-49 U.CARR (Carratelli units) before treatment and 218+/-33 U.CARR after treatment (p<0.05). A decrease of at least 10% was detected in every subject. In patients with peripheral vascular disease the mean (+/-SD) levels of free radicals were 404+/-42 U.CARR before treatment and 278+/-33 U.CARR after treatment (p<0.02). A decrease of at least 15% was detected in every patient (medium value 31%). CONCLUSIONS: The D-Roms test provides a simple, inexpensive and practical method to identify subjects with a high level of oxidative stress and to demonstrate the effect of treatment. The compound AR(D) Stenovit is effective in reducing circulating free radicals. Its action on the progression of atherosclerotic disease should be assessed in future studies.

Adult↗
PubMed1998

Evaluation of the tumorigenic and angiogenic potential of human fibroblast growth factor FGF3 in nude mice.

Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of human Kaposi's sarcoma (KS) tumor tissues examined, while almost no expression of FGF3 was found in normal skin. To further these studies, human FGF3 cDNA were constructed by the overlap-extension method. The proteins translated from two FGF3 cDNA, which differ only in the sequences preceding the AUG presumed to be the initiation codon, were shown to have the same molecular mass. This result suggests that translation of human FGF3, which is different from mouse FGF3, begins only at the AUG site. The human FGF cDNA was transfected into NIH3T3 cells. The NIH 3T3 cells transformed by FGF3 were then injected subcutaneously into athymic nude mice. Nodular lesions developed at the injection sites in all seven mice injected with the F3-1 cell clone, which showed high expression of FGF3, and in two out of six mice injected with the F3-2 cell clone, which expressed a low level of FGF3. Histopathological features of these tumors contained fascicles of spindle-shaped cells surrounding irregular endothelial lined vascular clefts, similar to those observed in human KS lesions. Immunohistochemical staining for factor V111 antigen revealed reactivity in multiple areas, especially in abundant vascular structures of the tumor sections examined. The expression of FGF3 together with the FGF receptors FGFR1, FGFR2, and FGFR3, was detected in the mouse tumors by Northern blot analysis. Our results indicate that tumors induced by FGF3-transformed NIH3T3 cells show some similarities to human KS tumors. In conclusion, our results demonstrate the potential tumorigenic and angiogenic role of human FGF3.

Animals↗
PubMed1998

The objective characterisation of ultrasonic carotid plaque features.

OBJECTIVE: To determine the influence of ultrasonic carotid plaque morphology on the incidence of ipsilateral hemispheric symptoms (IHS). DESIGN: Cross-sectional study. MATERIALS: A consecutive series of 80 patients (96 plaques) with more than 50% ICA stenosis was studied. METHODS: B mode ultrasonic images were captured and transferred to a computer on magneto-optic disk and standardised using linear scaling so that adventitia would have a grey scale median (GSM) value of 185-195 and blood 0-5. The GSM and the percentage of echolucent pixels (PEP) in plaques were determined to measure echodensity. Homogeneity, entropy, and contrast were also determined to measure spatial distribution (heterogeneity) of grey shades in each plaque. Each measurement was correlated to presence or absence of IHS. RESULTS: Twenty-five plaques were associated with IHS and 71 plaques were asymptomatic. In symptomatic plaques the mean of GSM was 23 and the mean of PEP was 70%, compared to 38 and 55% respectively in asymptomatic plaques (p = 0.02; Wilcoxon test). Sixty per cent of symptomatic plaques were associated with a homogeneity, entropy, and contrast values of > 0.2, < 2.95, < 150 respectively as compared to 40% in asymptomatic plaques. Multiple regression analysis revealed that the GSM and the PEP were the most significant variables (p = 0.001) that are related to presence or absence of IHS. CONCLUSION: This study indicates that computer aided analysis of ultrasonic B mode features of carotid plaques could identify a potentially high-risk subgroup (patients with IHS). A GSM less than 40 or PEP greater than 50% is a good predictor of IHS related to carotid plaques. The fact that these measurements are operator independent and performed after image standardisation should encourage their use in multicenter clinical trials where different operators and equipment are used.

Carotid Artery, Internal↗
PubMed1998

The effect of B-mode ultrasonic image standardisation on the echodensity of symptomatic and asymptomatic carotid bifurcation plaques.

BACKGROUND: To develop a method that allows B-mode ultrasonic images of carotid plaques to be standardised so that measurements of plaque echodensity become comparable and clinically useful. METHODS: Design. Cross sectional study. Setting. Teaching hospital, England. PATIENTS: a random consecutive series of 23 patients in part I, 19 in part II and 77 in part III. Measures. Part I: twenty-three images of carotid bifurcation plaques from 2 duplex scanners were digitised. Images were standardised by 4 observers so that the grey scale median (GSM) would be 0-5 for blood and 185-195 for adventitia. Part II: the effect of three different recording media: video, magneto-optical disk (MOD) and thermal paper on the echodensity of 19 plaques' images was determined. Part III: the echodensity of 91 carotid bifurcation plaques with greater than 50% stenosis was correlated to the presence or absence of ipsilateral hemispherical symptoms. RESULTS: Part I: the coefficient of variation (CV) among 4 observers was 0.7%, 0% and 4.7% after image standardisation for the adventitia, blood and plaques respectively. Part II: a near perfect agreement was obtained between the GSM of plaques from images on video and MOD (r = 0.97) after standardisation. Part III: after standardisation, the GSM of symptomatic plaques was lower (21 +/- 14.8) than in asymptomatic plaques (38 +/- 26) p = 0.002. Plaque echolucency was more likely to be associated with symptoms (relative risk 4.1 90% CI 1.8-9.4). CONCLUSIONS: Images from different scanners by different ultrasonographers and through different peripherals can be standardised so that measurements of plaque echodensity may become comparable. The method is recommended for use in future natural history studies on carotid plaques where stroke is the end-point.

Carotid Artery Thrombosis↗
PubMed1997

Expression and mutation of the tumor suppressor gene p53 in AIDS-associated Kaposi's sarcoma.

Alteration of the p53 gene is the most frequent event reported in human cancer, and p53 mutations have been observed in various neoplasms, including certain forms of skin cancer. Therefore, we postulated that p53 may also be involved in Kaposi's sarcoma associated with AIDS (AIDS-KS). Expression of the p53 gene was examined in freshly isolated tumor biopsy specimens from 15 patients with AIDS-KS. p53 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in both the AIDS-KS tumors and in normal skin control samples. p53 protein was detected in 4 of the 15 AIDS-KS specimens by immunohistochemical staining. Single-strand conformation polymorphism analysis PCR-products (PCR-SSCP) was used for detection of mutations of the p53 gene. One of the p53 positive AIDS-KS samples showed mobilized shifts in exon 6 suggestive of a mutation. Sequencing data showed the mutation to be located in codon 210. We examined other mechanisms that could stabilize p53 protein. SV40 large T antigen and adenovirus E1B protein were not found in the AIDS-KS specimens. MDM2, a p53-binding protein, was also detected in five of the AIDS-KS specimens, two of which also contained p53-positive cells. These observations suggest that the tumor suppressor gene p53 may be involved in the pathogenesis of AIDS-KS.

AIDS-Related Opportunistic Infections↗
PubMed1997

The ultrasonic evaluation of the carotid intima-media thickness and its relation to risk factors of atherosclerosis in normal and diabetic population.

High-resolution ultrasound provides an excellent tool for the non-invasive assessment of the severity of atherosclerosis. It allows the measurement of the common carotid artery (CCA) intima media thickness (IMT) which has been found to be a feasible and reliable method for the evaluation of the progression and regression of the disease. The aim of this study was to evaluate the influence of risk factors of atherosclerosis on the mean CCA IMT in both normal and non-insulin dependent diabetic (NIDDM) individuals and to determine the effect of diabetes as a major atherosclerotic risk factor on the CCA IMT. Four hundred and eighty-four subjects were studied, 244 normal individuals and 240 non insulin dependent diabetic patients. The right and left CCA IMT were measured using high resolution ultrasonography. Both in the normal and diabetic individuals, the mean CCA IMT was found to increase linearly with age (p < 0.01), was directly related to total serum cholesterol and triglyceride and inversely related to HDL-cholesterol (p < 0.01). Multiple linear regression analysis showed the most important risk factor influencing the CCA IMT and hence early athrosclerosis to be the presence of diabetes, followed by serum HDL-cholesterol (inverse relation), total cholesterol, age and serum triglyceride. This study has shown that high resolution ultrasonography can be used to evaluate the effect to risk factors on early atherosclerosis and could be used to monitor future clinical trails aiming to modify the progression of atherosclerosis in the population.

Adult↗
PubMed1996

Relative fasting hypoinsulinaemia and ultrasonically measured early arterial disease in type 2 diabetes. The SENDCAP Study Group, St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study.

Macrovasular disease is the most important cause of morbidity and mortality in Type 2 (non-insulin-dependent) diabetes. Dyslipidaemia and hyperinsulinaemia have been proposed as aetiological factors. This paper describes the interrelationships between fasting serum insulin, serum lipids, and the extent of ultrasonically measured early arterial disease in Type 2 diabetic subjects screened for entry into a prospective study set up to ascertain whether improving serum lipids can alter the progress of arterial disease in Type 2 diabetes. Measurements were made of the initima media thickness (IMT) in the carotid artery, and an arterial ultrasound score (AUS) based on appearances of both carotid and femoral arteries was calculated for 192 established Type 2 diabetic subjects, males and females, mean age 51 (range 35-66) years, median duration of diabetes 3.5 years, with no known cardiovascular disease. Multiple regression analysis showed that carotid IMT increased with age and was inversely related to serum insulin (variance accounted for, R2, = 8.8%, p = 0.0002). AUS increased with age and was related inversely to serum insulin, or to C-peptide when this was substituted in the model. In addition to age and serum insulin, AUS was positively associated with non-HDL cholesterol and negatively with HDL 3 cholesterol (R2 = 26%, p = 0.0001). Early thickening and damage to the arterial wall in Type 2 diabetes may be related to relative fasting hypoinsulinaemia.

Adult↗
PubMed1996

Ultrasonographic carotid plaque morphology in predicting stroke risk.

A number of new studies have provided evidence which suggests that carotid plaque surface characteristics and internal structure, as seen on ultrasonography, contribute to the development of cerebrovascular endpoints. This review is a critical presentation of the evidence that has emerged so far supporting the hypothesis that the ultrasonographic morphology of the carotid plaque may be an independent variable in predicting the risk of stroke. It is concluded that ultrasonographic plaque morphology should be used together with other local risk factors in prospective natural history studies which aim to identify a subgroup of patients at high risk of stroke.

Carotid Artery Diseases↗
PubMed1996

Histological verification of computerised carotid plaque characterisation.

The correlation between the computerised measurement of carotid plaque echogenicity on high resolution ultrasound imaging and plaque histology was studied in 52 patients undergoing carotid endarterectomy. Thirteen plaques were from asymptomatic patients, 15 were associated with amaurosis fugax, 10 with transient ischaemic attacks and 14 with stroke. Longitudinal images of the anterior and posterior component of each plaque were obtained by ATL Ultramark-4 Duplex scanner and were transferred to a computer. Using an image analysis program the median of the overall grey scale content of each plaque component was evaluated and used as a measure of echogenicity. Following carotid endarterectomy each plaque specimen was divided into anterior and posterior component and then fixed, oriented, sectioned and stained in the longitudinal plane corresponding to the ultrasound image. Plaque histology sections were then examined by computer morphometric analysis and the percentage surface areas of fibrous tissue, lipid deposits and haemorrhage were calculated. This was then correlated with the grey scale median for each plaque component. Plaques with a high lipid and haemorrhage content as established histologically had a low grey scale median (Spearman correlation r=-0.351, p<0.05) and those with a high fibrous content had a high grey scale median (r=0.411, p<0.001). This study has shown that computerised measurement of carotid plaque echogenicity correlates well with histology and could be used to predict plaque composition, thus identifying high risk plaques with high lipid and haemorrhage content.

Carotid Arteries↗
PubMed1996

The identification of the high risk carotid plaque.

OBJECTIVE: To determine the influence of carotid plaque morphology and severity of stenosis on symptoms of cerebrovascular disease and cerebral infarction. PATIENTS AND METHODS: One hundred and ninety patients with 329 carotid plaques producing 50-99% stenosis were studied. Carotid plaque echogenicity on ultrasonography was evaluated using computerised measurement of the median of the overall grey scale content (GSM). Heterogeneity was evaluated as the difference between the GSMs of the most echogenic and the most echolucent areas within each plaque and expressed as the heterogeneity index (HI). All patients had a CT brain scan and the presence of ipsilateral cerebral infarction noted. RESULTS: Cerebral infarction was more common in symptomatic than asymptomatic plaques (42% vs. 29%, p<0.02) and in echolucent than echogenic plaques (mean GSM of 37.8 vs. 29.7, p<0.01). Plaques with GSM below or equal to 32 were associated with a higher incidence of cerebral infarction as compared to those above this level, this was significant in both symptomatic and asymptomatic plaques. Symptomatic carotid plaque were less heterogenous than asymptomatic plaques. Plaques associated with cerebral infarction were less heterogenous than those not associated with infarction. CONCLUSION: This study has shown that the identification of the high risk carotid plaques, i.e. those associated with a high incidence of cerebral infarction is possible both in symptomatic and asymptomatic patients. The potential of such analysis in the identification of patients with asymptomatic carotid stenosis with high and low risk of stroke should be explored in a natural history study.

Carotid Stenosis↗
PubMed1996

A comparison of isotope penile blood flow and colour Doppler ultrasonography in the assessment of erectile dysfunction.

OBJECTIVES: To determine whether the measurement of penile blood flow by colour Doppler imaging (CDI) and the subjective impressions generated from CDI correlate with the results of measuring isotope penile blood flow (IPBF), and thus determine if CDI is a useful screening investigation for vasculogenic impotence. PATIENTS AND METHODS: The study comprised 37 men with impotence of > 6 months duration. All patients underwent CDI of the penis; the maximum systolic (vmax) and minimum diastolic velocity (vmin) were recorded. Video recordings of the CDI were reviewed subsequently with no knowledge of the erectile response. Twenty-seven patients then underwent measurement of IPBF. RESULTS: There was no relationship between the results obtained from IPBF and those from CDI, nor was there a significant difference between the vmax of patients identified as having arteriogenic impotence on IPBF and that of normal men or those with venous leakage on IPBF. There was no relationship between the subjective impressions from CDI and the results from IPBF, or with erectile response. CONCLUSIONS: There was no correlation between the results obtained on IPBF and those obtained from CDI; the latter is not useful in differentiating between venogenic and arteriogenic impotence in men who have failed to have a full response to papaverine.

Adult↗
PubMed1996

Changes in energy metabolism of calf muscle in patients with intermittent claudication assessed by 31P magnetic resonance spectroscopy: a phase II open study.

Energy status and metabolism in skeletal muscle of nine patients with peripheral arterial disease and suffering from intermittent claudication were evaluated using 31phosphorus magnetic resonance spectroscopy (MRS) before and after treatment for 3 months with propionyl-L-carnitine (PLC; 2 g/day p.o.). Maximum walking distance (MWD) was assessed on a standard treadmill (4 km/h, zero incline). For the group as a whole 31P MRS results did not change significantly with PLC. Although MWD increased by a mean of 36%, this change did not reach significance. However, when these variables were assessed with respect to the change in MWD, there were significant differences between those who increased MWD by > 30% (responders, R; n = 5) and those who did not (nonresponders, NR; n = 4). Compared with pretreatment values, during exercise the decrease in muscle pH in R relative to the decrease in phosphocreatine was less after PLC (p = 0.04). After exercise there was a significant inverse correlation between the changes in recovery half-time (t1/2) for phosphocreatine and in MWD (r = -0.91, p = 0.01). With PLC, Vmax increased in R (p = 0.04), but not in NR. For the patient group as a whole, the changes in Vmax and MWD correlated positively (r = 0.90, p = 0.01). This study helps to identify the changes in muscle metabolism that correlate with changes in exercise performance, and may accompany treatment with PLC.

Adenosine Diphosphate↗
PubMed1995

Computer-assisted carotid plaque characterisation.

OBJECTIVE: To determine the relationship between plaque echogenicity as measured by computer and the incidence of cerebral brain infarction. PATIENTS AND METHODS: Eighty-seven patients with 148 plaques producing more than 50% internal carotid artery stenosis were studied. Sixty-nine plaques were in asymptomatic patients, 35 were associated with amaurosis fugax, 19 with transient ischaemic attacks and 25 with stroke. All patients had a CT brain scan and the presence of ipsilateral cerebral infarction was noted. Images of the plaques obtained with an ATL Ultramark-4 Duplex scanner (7.5 MHz high resolution probe) were transferred to a computer. Using an image analysis program a histogram for each plaque was obtained with the number of pixels plotted against the grey scale (0-225). The median of the grey scale was used as a measure of echogenicity. RESULTS: Fifty-three (36%) of the 148 plaques were associated with ipsilateral CT brain infarction. Plaques with a grey scale median more than 32 (echogenic) were associated with an incidence of 11% (7/64) CT infarction. In contrast, plaques with grey scale median below or equal to 32 (echolucent) were associated with 55% (46/84) incidence of CT infarction (chi 2 = 30.35, p < 0.001, relative risk = 22, 95% confidence interval from 4.7 to 108). CONCLUSION: This study indicates that computer analysis of carotid plaque can identify high-risk carotid plaques. The potential of such analysis in the identification of asymptomatic high-risk patients should be explored in further studies.

Arteriosclerosis↗
PubMed1995

Calf muscle mitochondrial and glycogenolytic ATP synthesis in patients with claudication due to peripheral vascular disease analysed using 31P magnetic resonance spectroscopy.

1. We set out to define abnormalities of oxidative ATP synthesis, cellular proton efflux and the efficiency of ATP usage in gastrocnemius muscle of patients with claudication due to peripheral vascular disease, using data obtained by 31P magnetic resonance spectroscopy during aerobic exercise and recovery. 2. Eleven patients with moderate claudication were studied and results were compared with 25 age-matched control subjects. Changes in pH and phosphocreatine concentration during recovery were used to calculate the maximum rate of oxidative ATP synthesis (Qmax.) and the capacity of net proton efflux. Changes in pH and phosphocreatine concentration were used to estimate rates of non-oxidative and (indirectly) oxidative ATP synthesis throughout exercise, taking account of abnormalities in proton efflux during exercise. 3. In patients with claudication, slow post-exercise phosphocreatine recovery showed a 42 +/- 9% decrease in Qmax., and the slow ADP recovery was consistent with this. pH recovery was slow, showing a 77 +/- 9% decrease in the capacity for proton efflux. Both abnormalities are compatible with a substantial reduction in muscle blood flow. 4. During exercise, increased phosphocreatine depletion and intracellular acidification were a consequence of impaired oxidative ATP synthesis and the consequent increase in non-oxidative ATP synthesis, compounded by reduced proton efflux. The acidification prevented an increase in ADP concentration which could otherwise partially compensate for the oxidative defect. All these abnormalities are compatible with a reduced muscle blood flow. 5. In addition, initial-exercise changes in pH and phosphocreatine concentration implied a 44 +/- 5% reduction in 'effective muscle mass', necessitating an ATP turnover (per litre of muscle water) twice as high for given power output as in control muscle. Some of this is probably due to a localized loss of muscle fibres, but the rest appears to reflect reduced metabolic efficiency of the muscle. This is not a direct consequence of reduced blood flow, and may be related to change in muscle fibre type.

Adenosine Triphosphate↗