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Prognosis in node-negative primary breast cancer: a neural network analysis of risk profiles using routinely assessed factors.

BACKGROUND: The present study investigated complex time-dependent effects of routinely assessed factors on the risk of breast cancer recurrence over follow-up time, with a partial logistic artificial neural network (PLANN) model. PATIENTS AND METHODS: PLANN was applied to data from 1793 patients with node-negative breast cancer, not submitted to any adjuvant treatment and with a minimal potential follow-up of 10 years. RESULTS: The shape of the hazard function changed according to histology, which showed a time-dependent effect, partly modulated by estrogen receptors (ERs). Age and progesterone receptors (PgR) showed protective effects; the latter was more evident for short follow-up and high ER values. Tumour size and ER content showed time-dependent unfavourable effects at early and long follow-up times, respectively. Predicted values of disease recurrence probability at 2 years of follow-up showed that low steroid-receptor content, young age and large tumour size were associated with the highest risk of relapse. Although the oldest patients with high ER content seem to be those most protected overall, high risk predictions tend to spread also to higher steroid-receptor contents, intermediate ages and small tumour size, with an increase in follow-up time. CONCLUSION: PLANN with suitable visualisation techniques provided thorough insights into the dynamics of breast cancer recurrence for improving individual risk staging of node-negative breast cancer patients.

Breast Neoplasms↗

Radiotracer-based strategies to image angiogenesis.

Tumour-induced angiogenesis plays an important role in tumour progression. Great efforts are made to develop therapeutic strategies to interfere with this process resulting in the starvation of the tumour. However, strategies to monitor conventional therapies seems to be inappropriate to control these approaches. Thus, there is a keen interest in developing methods supplying information about the corresponding therapeutical effects. Several radiotracer-based approaches focused on different targets in the angiogenic process are currently investigated. One class of tracers is based on matrix metalloproteinases inhibitors. These compounds show promising results in in vitro assays. However, initial data from in vivo studies using murine tumour models could not confirm successful non-invasive monitoring of MMP activity yet. Another strategy uses a radiolabelled single chain fragment against the ED-B domain of fibronectin, an extracellular matrix protein. Promising results demonstrated selective accumulation of the tracer in the tumour vasculature of a murine tumour model. Most of the studies are concentrated on the development of radiolabelled antagonists of the integrin alpha(v)beta(3). This heterodimeric transmembrane glycoprotein is involved in the migration of activated endothelial cells during formation of new vessels. Different compounds have been labelled with (18F), (111)In, (99m)Tc, (90)Y and several iodine isotopes. In in vitro assays most of them revealed high alpha(v)beta(3) affinity and selectivity. Moreover, in different murine tumour models successful non-invasive determination of alpha(v)beta(3) expression has been shown. Some of these approaches indicate that tumour-induced angiogenesis can be monitored in animal studies. Nevertheless, translation of these approaches into clinical settings allowing visualisation of tumour-induced angiogenesis in patients needs still to be demonstrated.

Animals↗

Normative values of 99mTc-MIBI distribution in myocardium in males and females, as a basis for quantitative planar scintigraphic method for detection of coronary artery disease in patients of both sexes.

BACKGROUND: Radionuclide perfusion studies of myocardium are being performed using planar and tomographic (SPECT) procedures. The latter method enables better detection as well as assessment of localisation and severity of scintigraphically visualised perfusion defects. On the other hand, lower cost of planar procedures using 99mTc-MIBI as the tracer and their much wider availability in countries of Central and Eastern Europe could significantly increase the diagnostic potential of nuclear cardiology in this region. The aim of the study was an assessment of normal distribution of 99mTc-MIBI in the myocardium and generation of normative basis for quantitative planar scintigraphic procedure, aiming at detection of CAD in patients of both sexes. MATERIAL AND METHODS: The study was based on 250 patients. The reference (control) group consisted of 53 individuals (29 men, 24 women) with the low (< 10%) initial probability of CAD as estimated on basis of Diamond's tables. The second group included 197 patients (132 men, 65 women) with diagnosed CAD or with substantiated suspicion of its presence. In all patients of the latter group coronary angiography was performed and was used as the reference method for assessment of diagnostic efficacy of the scintigraphic procedure. RESULTS: The original own method of acquired data evaluation was based on creation of circumferential profiles of activity and on using the procedure of trend-fitting for obtaining average curves and their dispersion around the mean values. The mean profile curves were obtained for three projections (anterior, LAO 45 degrees and LAO 70 degrees ). These mean curves differed significantly between both sexes. In LAO 45 degrees projection the differences affected mostly the region of the septum and postero-lateral wall of the left ventricle (LV). In LAO 70 degrees projection differences were most pronounced in the antero-septal wall of the LV. CONCLUSION: Sensitivity, specificity and accuracy of CAD detection using the elaborated method, taking into account inter-sex differences, amounted to 86, 87 and 86% respectively in males, and correspondingly 81, 84 and 83% in females. The differences between corresponding indices for two sexes were statistically insignificant. For the whole group of patients the sensitivity, specificity and accuracy was 85, 86 and 85%, respectively.

Journal Article↗

Visualisation and measurement of the calcium message in guard cells.

We have applied several novel technologies to investigate the role of cytosolic free calcium [Ca2+]i in signal transduction in guard cells of Commelina communis L. Fluorescence ratio imaging and photometry together with the fluorescent Ca2+ indicator Indo-1 were used to directly visualise and measure dynamic spatial and temporal changes in [Ca2+]i in response to various exogenous stimuli. More subtle manipulation of the Ca2+ signal transduction pathway was achieved through the use of photoactivateable, caged Ca2+ and caged inositol-1,4,5-triphosphate (InsP3) released directly into the cytoplasm of the guard cell after microinjection. In these experiments, changes in [Ca2+]i were simultaneously monitored with the fluorescent Ca2+ indicator, Fluo-3. Resting levels of [Ca2+]i (100-200 nM) increased in response to elevated [Ca2+]e, lowering [K+]e, application of the ionophore A-23187 or cytosolic release of either Ca2+ or InsP3 from their caged forms. Stomatal closure was triggered if [Ca2+]i increased above a threshold of about 600 nM. Abscisic acid (ABA) had little effect on [Ca2+]i in the majority of cells studied, being elevated in only a minority of cells investigated. However, stomatal closure occurred in all cases after ABA application. This suggests that ABA acts through both Ca(2+)-independent and Ca(2+)-dependent pathways. The imaging data revealed a substantial heterogeneity in [Ca2+]i within the guard cell. Cytoplasmic regions, particularly near the nucleus, often showed marked elevations and sometimes oscillations. The origin and kinetics of the Ca2+ fluxes leading to the dynamic spatial patterns is discussed along with several new approaches directed towards identification of the source of the Ca2+. These methods include optical sectioning and 3-D reconstruction of both the endomembrane system and [Ca2+]i in living guard cells using confocal microscopy. Overall, our data is consistent with multiple sources for [Ca2+]i, including uptake across the plasma membrane and InsP3- or Ca(2+)-induced Ca2+ release from internal stores.

Calcium↗

Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS.

Transplantation of myelin-forming glial cells may provide a means of achieving remyelination in situations in which endogenous remyelination fails. For this type of cell therapy to be successful, cells will have to migrate long distances in normal tissue and within areas of demyelination. In this study, 40 Gy of X-irradiation was used to deplete tissue of endogenous oligodendrocyte progenitors (OPCs). By transplanting neonatal OPCs into OPC-depleted tissue, we were able to examine the speed with which neonatal OPCs repopulate OPC-depleted tissue. Using antibodies to NG-2 proteoglycan and in situ hybridisation to detect platelet-derived growth factor alpha-receptor Ralpha (PDGFRalpha) mRNA to visualise OPCs, we were able to show that neonatal OPCs repopulate OPC-depleted normal tissue 3-5 times more rapidly than endogenous OPCs. Transplanted neonatal OPCs restore OPC densities to near-normal values and when demyelinating lesions were made in tissue into which transplanted OPCs had been incorporated 1 month previously, we were able to show that the transplanted cells retain a robust ability to remyelinate axons after their integration into host tissue. In order to model the situation that would exist in a large OPC-depleted area of demyelination such as may occur in humans; we depleted tissue of its endogenous OPC population and placed focal demyelinating lesions at a distance (< or =1 cm) from a source of neonatal OPCs. In this situation, cells would have to repopulate depleted tissue in order to reach the area of demyelination. As the repopulation process would take time, this model allowed us to examine the consequences of delaying the interaction between OPCs and demyelinated axons on remyelination. Using this approach, we have obtained data that suggest that delaying the time of the interaction between OPCs and demyelinated axons restricts the expression of the remyelinating potential of transplanted OPCs.

Animals↗

Detection of maternal cell contamination in amniotic fluid cell cultures using fluorescent labelled microsatellites.

A rapid PCR based assay was used to ascertain the presence of maternal cell contamination (MCC) in amniotic fluid cell cultures and to exclude MCC in cases where cytogenetic analysis was possible only from one primary cell culture. Six 6-carboxyfluorescein (FAM) and three 6-carboxyfluorescein hexachloride (HEX) labelled primer sets were used to amplify two tetra- and seven dinucleotide repeat polymorphisms. The PCR amplifications were multiplexed in (three) three primer set reactions and visualised on an Applied Biosystems 373A sequencer running Genescan 672 software. The microsatellite products obtained from 200 amniotic fluid cell cultures where the karyotype was female were compared against corresponding maternal blood PCR products. A single case of MCC was detected indicating the usefulness of such assays. We suggest that screening for MCC should be considered in instances where the amniotic fluid sample is bloodstained or was obtained with difficulty, or where the karyotype is female and chromosome analysis is not possible from more than one primary cell culture.

Amniocentesis↗

VIEWER: a program for visualising, recording, and analysing animal behaviour.

In order to determine the influence of environmental interventions, medical substances, drugs, or diseases on an animal, it is a common to observe the behaviour of the animal in the open field or in other environments. Changes in animal behaviour can be the first indicators for an influence of a substance or an intervention on the organism and certain kinds of behavioural changes can permit speculations about the underlying physiological mechanisms. Behavioural properties which are of interest in this respect are movement parameters such as velocity or direction, activity patterns, spatial distribution and occurrence of several types of standard behaviours of an animal. Observation of simple behaviours such as determining the average activity level can help to detect general changes of the internal state of an animal, while changes in complex behaviours may point to specific influences of a substance or an intervention. Our system 'VIEWER' uses a microcomputer (IBM-compatible PC running WINDOWS 95, WINDOWS 98, WINDOWS NT, or WINDOWS 2000), a low budget framegrabber card (e.g. WinTV, Hauppauge) and a standard black-and-white video camera (if necessary with infrared sensitivity). The software records the position of the animal online with a sample rate of up to 25 frames/s. After identification of the animal in the arena, animal location and orientation with respect to time is determined. In addition, movement velocity and direction, general activity level, and several other behavioural parameters which can include complex behavioural patterns are processed online. Data are presented as graphics and/or tables. Results may also be exported into those programs that are capable of importing graphics (wmf or bmp format) or ASCII-files. VIEWER offers an inexpensive, fast and easy way for analysing simple and complex behaviours of many species of animals in a variety of behavioural situations.

Animals↗

Sinus venosus syndrome: atrial septal defect or anomalous venous connection? A multiplane transoesophageal approach.

OBJECTIVE: To discuss the anatomical features of sinus venosus atrial defect on the basis of a comprehensive transoesophageal echocardiography (TOE) examination and its relation to surgical data. METHODS: 24 patients (13 men, 11 women, mean (SD) age 37 (17) years, range 17-73 years) with a posterior interatrial communication closely related to the entrance of the superior (SVC) or inferior vena cava (IVC) who underwent TOE before surgical repair. Records of these patients were retrospectively reviewed and compared with surgical assessments. RESULTS: In 13 patients, TOE showed a deficiency in the extraseptal wall that normally separates the left atrium and right upper pulmonary vein from the SVC and right atrium. This deficiency unroofed the right upper pulmonary vein, compelling it to drain into the SVC, which overrode the intact atrial septum. In three patients, TOE examination showed a defect in the wall of the IVC, which continued directly into the posterior border of the left atrium. Thus, the intact muscular border of the atrial septum was overridden by the mouth of the IVC, which presented a biatrial connection. In the remaining eight patients, the defect was located in the muscular posterior border of the fossa ovalis. A residuum of atrial septum was visualised in the superior margin of the defect. Neither caval vein overriding nor anomalous pulmonary vein drainage was present. CONCLUSIONS: Sinus venosus syndrome should be regarded as an anomalous venous connection with an interatrial communication outside the confines of the atrial septum, in the unfolding wall that normally separates the left atrium from either caval vein. It results in overriding of the caval veins across the intact atrial septum and partial pulmonary vein anomalous drainage. It should be differentiated from posterior atrial septal defect without overriding or anomalous venous connections.

Adolescent↗

Bilirubin, ferritin, D-dimers and erythrophages in the cerebrospinal fluid of patients with suspected subarachnoid haemorrhage but negative computed tomography scans.

AIM: To assess the diagnostic value of cerebrospinal fluid (CSF) spectrophotometry, cytology, ferritin, and D-dimer measurements in the investigation of suspected subarachnoid haemorrhage in patients with negative or equivocal computed tomography (CT) scans. METHODS: CSF specimens submitted for assessment of xanthochromia were examined for erythrophages using a cytospin preparation stained with Wright's stain, for ferritin using the Ciba-Corning Magic IRMA assay, D-dimers using the Dimertest 2 latex agglutination slide test, and for bilirubin by scanning spectrophotometry. The patients were divided into three groups for data analysis and the results compared with the existing methods, CT, and angiogram results. Final diagnoses were reviewed by a consultant neurologist. RESULTS: Thirty six patients were recruited. In those patients with confirmed subarachnoid haemorrhage CSF cytology had a low sensitivity and there were false negative results with both the D-dimer and ferritin assays. Eleven patients with a negative or equivocal CT scan underwent angiography, but only one aneurysm and no arterio-venous malformations or bleeding points were identified. In the patient with the aneurysm there was no laboratory evidence of subarachnoid haemorrhage. Six patients had CSF abnormalities detected by the special tests only and in none of these cases was subarachnoid haemorrhage confirmed. All results were normal in four out of five cases of traumatic tap. CONCLUSIONS: This is a small study, but it shows that, depending on the timing of the lumbar puncture, false negative results can occur with both ferritin and D-dimer measurements. It suggests that neither of these tests adds significantly to the information provided by CT, visualisation of CSF, and spectrophotometry and confirms that, despite the use of spectrophotometry, D-dimer and ferritin assays in selecting patients for angiography, the proportion of patients with negative CT scans and colourless CSF with demonstrable vascular lesions remains low.

Bilirubin↗

Multi-dimensional visualisation of laboratory findings and functional test results for analysing the clinical course of disease in medicine.

The illustration of a patient's history by a graphical primitive is discussed. Illustration technology is presented which simultaneously represents quantitative examination findings (e.g., laboratory values) and qualitative findings (e.g., from function diagnostics) by a single geometrical figure. Depending on the medical results, this figure takes on characteristic forms which can be identified as patterns typical for a specific disease. The procedure developed is integrated in a user interface which is implemented in the form of a computerized medical record for use on a pentop computer. This portable computer assists the physician during ward rounds, supplies additional, intelligence-based information, serves quality control, and streamlines working procedures making them more efficient.

Clinical Laboratory Information Systems↗

A functional bipartite nuclear localisation signal in the cytokine interleukin-5.

Interleukin (IL)-5 is central in regulating eosinophilia in allergic disease and parasitic infections. We have identified a bipartite nuclear localisation signal (NLS) within amino acids 95-111 of human IL-5 (hIL-5), also present in mouse IL-5 (mIL-5). hIL-5 and mIL-5 were labelled fluorescently, and nuclear uptake subsequent to membrane binding and internalisation by intact receptor expressing cells visualised and quantified using confocal laser scanning microscopy. hIL-5 and mIL-5 were shown to be transported to the nucleus in in vivo and in vitro nuclear protein import assays. The hIL-5 NLS was able to target a heterologous protein to the nucleus both in vivo and in vitro. Mutations within the proximal arm of the NLS abrogated nuclear targeting activity, confirming its bipartite nature. The results imply a nuclear signalling role for IL-5 additional to pathways linked to the membrane receptor system.

Amino Acid Sequence↗

GENOLYTE: a PC-based computer program for visualisation of genomic DNA sequences.

This paper describes the program "GENOLYTE" which has been developed for the visualisation and identification of the global and local patterns of long genomic DNA sequences quickly in a few minutes, with the aid of a microcomputer. Apart from global and local identification, GENOLYTE comparatively depicts the similarity of two or more than two genomic DNA sequences. The utility of the program has been demonstrated by analysing the complete mitochondrial DNA sequences (taken from EMBL databank) as an example and the results are discussed from therein. The program written in TURBO C++ has the following minimum requirements: (i) PC 386 AT, (ii) SVGA colour monitor, (iii) the [BGI] directory of TURBO C++ version 3.0.

Animals↗

99mTc-Demotate 1: first data in tumour patients-results of a pilot/phase I study.

Somatostatin receptor (SSTR) scintigraphy with indium-111 DTPA-octreotide has become a routine diagnostic procedure in oncology. However, it suffers some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of (111)In. We have recently been involved in the development of a new tetraamine-functionalised [Tyr(3)]octreotate derivative (Demotate 1) that can be easily labelled with technetium-99m at high specific activities. (99m)Tc-Demotate 1 showed promising properties in preclinical studies. In this study we report on the first experience with (99m)Tc-Demotate 1 in patients. Six patients (mean age 56 years) with carcinoid tumours ( n=2) or endocrine pancreatic tumours ( n=4) with previously positive SSTR scintigraphy were enrolled in the study. Patients were injected with 500-600 MBq (99m)Tc-Demotate 1. Clinical and laboratory parameters were controlled up to 3 months p.i. Blood samples were taken at various time points up to 24 h p.i., and urine was collected up to 24 h. Whole-body images were acquired at 15-30 min, 1-2 h, 4 h and 24 h p.i. with additional single-photon emission tomography imaging at 1-4 h. Blood excretion was very rapid, with <2%ID in plasma after 1 h, and urinary excretion <20% ID after 6 h. Two patients complained of mild gastrointestinal problems and paraesthesia, but no other adverse reactions were observed. SSTR-positive tumours were rapidly visualised as early as 15 min p.i., with maximum tumour uptake (up to 19% ID) and tumour/organ ratios as early as 1 h p.i. Organs of predominant physiological uptake were the spleen and the kidneys, with no intestinal excretion detectable up to 24 h. (99m)Tc-Demotate 1 detected 11 lesions while In-Oct detected ten; differences in uptake behaviour were observed in three patients. This study shows for the first time that peptides derivatised with a tetraamine ligand for labelling with (99m)Tc show suitable properties for receptor imaging in patients. (99m)Tc-Demotate 1 is a promising agent for the visualisation of SSTR-positive lesions in patients, allowing rapid imaging as early as 1 h p.i.; some differences are observed in pharmacokinetic behaviour compared with (111)In-DTPA-octreotide.

Aged↗

Baculovirus-mediated high level expression of a human thiopurine methyl transferase.

We have expressed the human thiopurine methyltransferase cDNA in a baculovirus vector in Sf21 (Spodoptera frugiperda) cells. This system expresses the enzyme at levels such that the thiopurine methyltransferase enzyme may be readily visualised by Coomassie blue stained sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expressed enzyme catalysed the methylation of 6-mercaptopurine with an apparent Km of 892 microM, similar to that observed in human liver cytosol ie. 657 microM however, the Vmax was 13,500 pmole/mg/min, which is approximately 400 times higher than the Vmax observed in human liver cytosol ie. 33 pmole/mg/min. The thiopurine methyltransferase inhibitors 6-thioxanthine, p-methoxybenzoic acid and 3,5-dimethoxy benzoic acid were found to be potent inhibitors of the expressed enzyme.

Animals↗

Three-dimensional MR imaging in the assessment of physeal growth arrest.

The purpose of this study is to describe an imaging method for identifying and characterising physeal growth arrest following physeal plate aggression. The authors describe the use of three-dimensional MRI performed with fat-suppressed three-dimensional spoiled gradient-recalled echo sequences followed by manual image reconstruction to create a 3D model of the physeal plate. This retrospective series reports the analysis of 33 bony physeal bridges in 28 children (mean age 10.5 years) with the use of fat-suppressed three-dimensional spoiled gradient-recalled echo imaging and 3D reconstructions from the source images. 3D reconstructions were obtained after the outlining was done manually on each source image. Files of all patients were reviewed for clinical data at the time of MRI, type of injury, age at MRI and bone bridge characteristics on reconstructions. Twenty-one (63%) of the 33 bridges were post-traumatic and were mostly situated in the lower extremities (19/21). The distal tibia was involved in 66% (14/21) of the cases. Bridges due to causes other than trauma were located in the lower extremities in 10/12 cases, and the distal femur represented 60% of these cases. Of the 28 patients, five presented with two bridges involving two different growth plates making a total of 33 physeal bone bars. The location and shape of each bridge was accurately identified in each patient, and in post-traumatic cases, 89% of bone bars were of Ogden type III (central) or I (peripheral). Reconstructions were obtained in 15 min and are easy to interpret. Volumes of the physeal bone bridge(s) and of the remaining normal physis were calculated. The bone bridging represented less than 1% to 47% of the total physeal plate volume. The precise shape and location of the bridge can be visualised on the 3D reconstructions. This information is useful in the surgical management of these deformities; as for the eight patients who underwent bone bar resection, an excellent correspondence was found by the treating surgeon between the MRI 3D model and the per-operative findings. Accurate 3D mapping obtained after manual reconstruction can also visualise very small physeal plates and bridges such as in cases of finger physeal disorders. MR imaging with fat-suppressed three-dimensional spoiled gradient-recalled echo sequences can be used to identify patterns of physeal growth arrest. 3D reconstructions can be obtained from the manual outlining of source images to provide an accurate representation of the bony bridge that can be a guide during surgical management.

Adolescent↗

Visualising the dissociation of sequence selective ligands from individual binding sites on DNA.

We have used a modification of the footprinting technique to measure the dissociation of mithramycin, echinomycin and nogalamycin from their binding sites in a natural DNA fragment. Complexes with radiolabelled DNA were dissociated by addition of unlabelled DNA. Samples were removed at various times and subjected to DNase I digestion, and the rate of dissociation from each site was estimated from the time-dependent disappearance of the footprints. For echinomycin the slowest rate of dissociation is from ACGT, while the slowest site for mithramycin contains four contiguous guanines. The dissociation of nogalamycin is extremely slow, even from its weaker sites; the slowest rate was from ACGTA, which took longer than 4 h, even at 37 degrees C.

Base Sequence↗

The role of two-dimensional echocardiography in the detection of potentially embolic intracardiac masses in patients with cerebral ischaemia.

The M-mode and two dimensional echocardiographic data of 62 consecutive cardiac patients referred from neurology centres were analysed retrospectively to establish the use of these techniques in detecting underlying cardiac pathology. All patients had presented initially to a neurologist with transient or permanent focal cerebral or retinal ischaemia, and had been referred for cardiac assessment after neurological investigations failed to establish the underlying cause of the neurological event. Patients were divided into two groups. In 30 patients the referring neurologist had found no evidence of cardiac disease (Group I); in the other 32 patients either heart disease or an arrhythmia had been diagnosed prior to cardiac referral (Group II). One of the patients in Group I had echocardiographic evidence of mitral valve prolapse not detected by the neurologist prior to referral; no cardiac pathology was recognised in the other 29 patients in this group. In seven of the 32 (22%) patients from Group II, a cardiac mass presumed responsible for the neurological manifestations was demonstrated echocardiographically, and in six of these histological confirmation was obtained following surgery or at necropsy. Two dimensional echocardiography was the only investigation which visualised the intracardiac pathology in four patients. In the remaining three patients, valve vegetations (two cases) and an atrial tumour (one case) were demonstrated by both echocardiographic methods. In patients with either clinical evidence of cardiac disease or an arrhythmia who have experienced one or more episodes of cerebral or retinal ischaemia, the presence of an intracardiac mass is not uncommon. Two dimensional echocardiography was the method of choice for detecting cardiac thrombus but the use of both methods of ultrasound should be considered as complementary techniques in the investigation of these cases. Routine echocardiography is unlikely to be of value in screening patients who have had a cerebrovascular event and who do not have clinical evidence of heart disease or an arrhythmia.

Adolescent↗

[Evaluation of diastolic function of in patients addicted to recreational cocaine].

BACKGROUND AND AIMS: The recreational use of cocaine is associated with cardiovascular pathologies, such as ischemic cardiopathy, myocarditis and cardiomyopathies, owing to the increased catecholamine stimulus, a propensity to coronary spasm, increased coagulative activity and inflammatory and degenerative phenomena of myocardiac cells. Early alterations of the diastolic phase may be visualised by evaluating the diastolic Doppler pattern of left ventricular filling. METHODS: For this purpose the authors compared blood pressure, heart rate, heart mass, protodiastolic (E wave) and telediastolic (A wave) filling rate and their ratio (E/A) on the Dopper mitral diastolic profile in a group of 10 patients addicted to the recreational use of cocaine (mean age 33 +/- 7) with those of 10 normal subjects (mean age 34 +/- 2). RESULTS: Patients using cocaine presented mean systolic arterial blood pressures of 130 +/- 12 versus 127 +/- 8 in control subjects (p = ns); mean heart rate was statistically significant with 98 +/- 14 versus 76 +/- 12 in controls (p < 0.05). There were no differences in cardiac mass between the two groups. In cocaine addicts the speed of the E wave was significantly slower: 58.4 +/- 8.6 versus 73 +/- 7.4 cm/sec (p < 0.05), and the speed of the A wave was significantly higher: 70.5 +/- 10.5 versus 62.6 +/- 4.3 cm/sec (p < 0.05), when compared with normal controls subjects; the E/A ratio of cocaine addicts was lower (0.75 +/- 0.34) compared to normal subjects (1.07 +/- 0.7), (p < 0.05). CONCLUSIONS: These data show that patients addicted to the recreational use of cocaine show preclinical alterations of the left ventricular diastolic phase prior to the onset of clinically evident pathologies.

Adult↗