The risk model of choice for coronary surgery in the UK.
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Coronary Artery Bypass↗
Biomedical subjects
M Petrou
Publications and source records attributed to M Petrou.
Diagnostic features of Alzheimer's disease extracted from PET sinograms.
Texture analysis of positron emission tomography (PET) images of the brain is a very difficult task, due to the poor signal to noise ratio. As a consequence, very few techniques can be implemented successfully. We use a new global analysis technique known as the Trace transform triple features. This technique can be applied directly to the raw sinograms to distinguish patients with Alzheimer's disease (AD) from normal volunteers. FDG-PET images of 18 AD and 10 normal controls obtained from the same CTI ECAT-953 scanner were used in this study. The Trace transform triple feature technique was used to extract features that were invariant to scaling, translation and rotation, referred to as invariant features, as well as features that were sensitive to rotation but invariant to scaling and translation, referred to as sensitive features in this study. The features were used to classify the groups using discriminant function analysis. Cross-validation tests using stepwise discriminant function analysis showed that combining both sensitive and invariant features produced the best results, when compared with the clinical diagnosis. Selecting the five best features produces an overall accuracy of 93% with sensitivity of 94% and specificity of 90%. This is comparable with the classification accuracy achieved by Kippenhan et al (1992), using regional metabolic activity.
Adult↗
Influence of clenbuterol treatment during six weeks of chronic right ventricular pressure overload as studied with pressure-volume analysis.
OBJECTIVES: Chronic pressure overload cardiac hypertrophy produces ventricular dysfunction. There is evidence that clenbuterol, a beta(2)-adrenoceptor agonist, produces cardiac hypertrophy with preserved function in rodents. We sought to determine the cardiac hypertrophic effects of clenbuterol on the thin-walled ventricles of large animals undergoing chronic pressure overload by means of pulmonary artery banding. METHODS: Right ventricular pressure-volume loops were obtained in open-chest sheep before and after 6-1/2 weeks of pulmonary artery banding by using micromanometer conductance catheters. Animals were randomly assigned to treatment with either saline solution (n = 7) or clenbuterol (n = 8). Treatment was started immediately after pulmonary artery banding. RESULTS: Acute pulmonary artery banding increased the right ventricular systolic pressure equally in both groups (saline group, 23.9 +/- 3.3 to 48.1 +/- 9.7 mm Hg; clenbuterol group, 24.3 +/- 2.8 to 48.6 +/- 10.7 mm Hg [mean +/- standard deviation]). Six weeks of treatment produced no significant differences in the body weight, heart weight, heart/body weight ratio, right ventricular wall thickness, heart rate, and stroke volume between the groups. However, the slope of the end-systolic pressure-volume relation and the slope of the first derivative of the right ventricular developed pressure/end-diastolic volume relation were significantly increased when compared with baseline values in clenbuterol-treated animals but not in saline-treated animals. CONCLUSION: Clenbuterol treatment during pulmonary artery banding improves systolic function of the chronically pressure-overloaded right ventricle. This has important implications for the use of pharmacologic agents in modulating cardiac adaptation.
Adrenergic beta-Agonists↗
A national register for surveillance of inherited disorders: beta thalassaemia in the United Kingdom.
OBJECTIVE: To demonstrate the value of a national register for surveillance of services for an inherited disorder. METHODS: Data from the United Kingdom Thalassaemia Register and the United Kingdom Register of Prenatal Diagnosis for Haemoglobin Disorders were combined in a database; these registers include all fetuses known to have been diagnosed with beta thalassaemia major, beta thalassaemia intermedia, or haemoglobin E/beta thalassaemia in the United Kingdom. Data were extracted to show outcomes (selective abortion or live birth) of all fetuses and the status of those born with a disorder (alive, dead, successful bone marrow transplant, or lost to follow-up) by parents' region of residence and ethnicity. FINDINGS: At the end of 1999 the register included 1074 patients, 807 of whom were alive and residing in the United Kingdom. A successful bone marrow transplant has been performed for 117 out of 581 (20%) patients born since 1975. Residents of Pakistani origin are now the main group at risk in the United Kingdom, replacing residents of Cypriot origin. This has led to a marked shift in the need for services from the south-east of England to the Midlands and the north of England. Despite the acceptability of prenatal diagnosis, the proportion of affected births remains 50% higher than would be expected, reflecting a widespread failure to deliver timely screening and counselling to carriers. Even though effective treatment is available the annual number of deaths is rising, indicating that better tolerated treatments are needed. CONCLUSION: A national diagnosis register is a powerful instrument for monitoring the treatment and prevention of inherited disorders and for highlighting correctable shortcomings. In view of the increasing possibilities for genetic screening there is a strong case for central funding for such databases within modern health services.
Adolescent↗
Informed choice in genetic screening for thalassaemia during pregnancy: audit from a national confidential inquiry.
OBJECTIVE: National audit of informed choice in antenatal screening for thalassaemia. DESIGN: Audit from the UK Confidential Enquiry into Counselling for Genetic Disorders. SETTING: Thalassaemia module of the UK Confidential Enquiry into Counselling for Genetic Disorders. SUBJECTS: 138 of 156 couples who had had a pregnancy affected by a major beta thalassaemia from 1990 to 1994. MAIN OUTCOME MEASURES: How and when genetic risk was identified for each couple, and whether and when prenatal diagnosis was offered. RESULTS: Risk was detected by screening before or during the first pregnancy in 49% (68/138) of couples and by diagnosis of an affected child in 28% (38/138) of couples. Prenatal diagnosis was offered in 69% (274/400) of pregnancies, ranging from 94% (122/130) for British Cypriots to 54% (80/149) for British Pakistanis and from 90% in the south east of England to 39% in the West Midlands. Uptake of prenatal diagnosis was 80% (216/274), ranging from 98% (117/120) among British Cypriots in either the first or second trimester to 73% (35/48) among British Pakistanis in the first trimester and 39% (11/28) in the second trimester. A demonstrable service failure occurred in 28% (110/400) of pregnancies, including 110 of 126 where prenatal diagnosis was not offered and 48 of 93 that ended with an affected liveborn infant. CONCLUSION: Although antenatal screening and counselling for haemoglobin disorders are standard practices in the United Kingdom, they are delivered inadequately and inequitably. An explicit national policy is needed, aiming to make prenatal diagnosis in the first trimester available to all couples and including ongoing national audit.
Choice Behavior↗
Long-term effect of prospective detection of high genetic risk on couples' reproductive life: data for thalassaemia.
Prospective risk detection with availability of prenatal diagnosis is the best service currently available for couples at high genetic risk Here we describe the long term effect of this service on the reproductive life of 102 couples at risk of thalassaemia, whose risk was detected prospectively by carrier screening, who made use of prenatal diagnosis, and where the woman is now over 40. Overall outcome for couples is described in terms of number of favourable versus unfavourable pregnancy outcomes. (A favourable pregnancy outcome = unaffected livebirth, or affected livebirth resulting from informed parental choice.) The 102 couples had a total of 356 pregnancies, including 302 viable pregnancies, and 88% achieved a family unburdened by thalassaemia. 68% of viable pregnancies had a favourable outcome, but only 43% of couples had only favourable outcomes, and 26% lost two or more viable wanted pregnancies. When early losses are included 58% of pregnancies had a favourable outcome, but only 30% of couples had only favourable outcomes, and 41% lost two or more pregnancies. Even with the best available service, at risk couples remain victims of chance, and a significant minority experience great difficulty in obtaining even one healthy child. Research is needed on approaches that may allow couples better control of reproductive outcomes.
Adult↗
A global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion. Global Antifungal Surveillance Group.
An improved fluconazole 25-mg disk diffusion method was used to test the susceptibility of 20,900 consecutively isolated clinical strains of Candida species from 40 hospital laboratories in 26 countries. The procedure is similar to the National Committee for Clinical Laboratory Standards (NCCLS) M2-A6 method for testing bacteria, except Mueller-Hinton agar is supplemented with 2% glucose and 0.5 mcg/mL methylene blue. Plates were incubated at 35 degrees C and read after 18 to 24h. Tentative zone interpretive criteria were based on the correlation by regression analysis with the NCCLS M27-A Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: > =19mm Susceptible, < = 12mm Resistant, and 13-18 mm Susceptible-Dose Dependent. Of 14,368 isolates of Candida albicans, 2,073 C. glabrata, 869 C. tropicalis, 752 C. parapsilosis, and 351 C. krusei, 99%, 67%, 90%, 94%, and 26%, respectively, were susceptible in vitro to fluconazole. All study sites used the BIOMIC System to electronically read zones on plates, interpret, record test results and verify quality control data. This is the largest study to date that evaluated a broad range of sequentially collected yeasts from various infections and different types of hospitals. The modified disk testing procedure is facile and economical to perform and offers a reproducible and accurate means to assess the in vitro susceptibility of Candida species to fluconazole.
Antifungal Agents↗
The long-term morbidity of pleuroperitoneal shunts in the management of recurrent malignant effusions.
OBJECTIVE: Over the last 15 years we have managed patients with malignant pleural effusion, using a single procedure with thoracoscopy and talc pleurodesis or shunt as appropriate. Talc pleurodesis remains our primary treatment option but in those patient shown to have the 'trapped lung syndrome', in whom pleurodesis would fail, we have been using a pleuroperitoneal shunt. METHODS: This retrospective review was undertaken to evaluate the mortality and morbidity of pleuroperitoneal shunts in the management of malignant pleural effusions and to assess their long-term results. Three hundred and sixty patients were treated for malignant effusions during the period 1983-1998, 160 (44.4%) of whom had a pleuroperitoneal shunt inserted. There were no intraoperative deaths and the hospital mortality was three patients (1.87%). Follow up was available for 88.1% of patients. The median survival of all malignant cases was 7.7 months (range 1-72 months). Mesothelioma patients survived somewhat longer with a median survival of 10.1 months. RESULTS: Shunt complication occurred in 21 patients (14.8%). Twelve patients developed shunt occlusion, requiring revision in five and replacement in seven. The shunt was removed in eight patients due to skin erosion in one patient and infection in seven patients. The distal limb of shunt was broken in one patient and the shunt was replaced. One patient developed malignant seeding along the chest wall at the site of shunt insertion but there were no incidences of peritoneal deposits. Effective palliation was achieved in 95% of patients. CONCLUSIONS: Pleuroperitoneal shunt insertion provides effective and safe palliation for malignant pleural effusion when associated with the 'trapped lung syndrome'. There are however complications which require revision or shunt removal. There is no evidence that peritoneal deposits result from pleuroperitoneal shunting.
Adult↗
Thalassaemia control in developing countries--the Sri Lankan perspective.
Beta thalassaemia is a Mendelian recessive disorder. The economic and social cost of the disease is high due to patients' life long need for monthly blood transfusions and treatment with desferrioxamine, an iron chelating agent. Wider availability of cheaper drugs is on the horizon. If there is no concomitant reduction in the number of new thalassaemia major births, there will be a cumulative increase in numbers requiring treatment. The frequency and severity, and the economic and social costs of thalassaemia, support the case for the introduction of a carrier screening and counselling program in Sri Lanka. A three-pronged plan emphasising professional, political and public education in outlined.
Birth Rate↗
Prenatal diagnosis of beta-thalassaemia in Pakistan: experience in a Muslim country.
A service for prenatal diagnosis of beta-thalassaemia was introduced in Pakistan in May 1994. Two renowned Islamic scholars, consulted before the service was introduced, ruled that a pregnancy can be terminated if the fetus is affected by a serious genetic disorder, and if termination is before 120 days (17 weeks) of gestation. During the first 3(1/2) years of the service 300 couples requested the test. Almost all the couples had been informed by their treating doctors. Most diagnoses were made between 10 and 16 weeks of gestation, and only 15 (5%) were reached after the 16th week. DNA analysis was by the amplification refractory mutation system (ARMS). A multiplex ARMS was developed in which three primer combinations identified the mutations in 91.5% of the couples. In 13 couples (4. 3%) linkage analysis was required for the fetal diagnosis. In 47/53 (88.7%) women carrying an affected fetus the pregnancy was terminated. In six cases it was declined principally on religious grounds. Postnatal confirmation of the prenatal diagnosis was possible in 117 unaffected children. One year after the start of the service, interviews with 141 couples with an affected child showed that 72% knew of the availability of prenatal diagnosis. Thirty-two of the informed couples had had a pregnancy, but only 18 (56%) used prenatal diagnosis. The main reasons for non-utilization of prenatal diagnosis were the cost of the test and fear of undergoing the test, though some gave no clear explanation. This study demonstrates that prenatal diagnosis is feasible and acceptable in a Muslim country such as Pakistan.
Attitude↗
Accuracy of prenatal diagnosis for haemoglobin disorders in the UK: 25 years' experience.
We have reviewed the accuracy of prenatal diagnosis for the thalassaemias and sickle cell disorders performed for UK residents since the service began in 1974. Prenatal diagnosis has been performed in 3254 pregnancies: 517 by fetal blood analysis, 681 by Southern blotting and 2056 by polymerase chain reaction (PCR) methods, the majority using the amplification refractory mutation system (ARMS). The number of homozygotes diagnosed was 808 (24.8%). Twenty-five diagnostic errors have been recorded, ten arising from non-laboratory errors (0.31%) and 15 due to technical problems associated with the diagnostic techniques. The latter group consisted of eight misdiagnoses by globin chain synthesis (1.55%), five by Southern blot analysis (0.73%) and two by PCR methods (0. 10%). The data show that the accuracy of prenatal diagnosis has improved with each development of diagnostic technique, and confirms that prenatal diagnosis of beta-thalassaemia and sickle cell disorders by ARMS-PCR is very accurate and reliable. The overall error rate for prenatal diagnosis by PCR methods in the UK is now 0. 41%.
Blotting, Southern↗
Clenbuterol increases stroke power and contractile speed of skeletal muscle for cardiac assist.
BACKGROUND: Skeletal muscle assist (SMA) may be limited by loss of power, slowing of contraction and relaxation, and atrophy of the transformed latissimus dorsi muscle (LD). Clenbuterol (clen), a beta2-adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep. METHODS AND RESULTS: The following 4 groups were used: A (n=6), untrained controls; B (n=6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240- microsec pulse duration, 35 Hz, 3 to 6 pulses per burst, and up to 40 bursts per minute); C (n=6), clen-treated (0.5 mg/kg SC) for 12 weeks; and D (n=6), clen+trained. In a terminal experiment, the mobilized LD was wrapped around a rubber aorta of a mock circulation and stimulated to contract 40 times per minute. Group A had an initial mean pressure augmentation (DeltaP) of 24.6 mm Hg and stroke power of 2.28 W/kg, but both fell to <20% of their original values by 15 minutes because of fatigue (P<0.005). Group B was fatigue-resistant, with a DeltaP and stroke power at 60 minutes of 13 mm Hg (70% of initial) and 0.34 W/kg (39% of initial), respectively. The performance of group C was similar to that of controls. In group D, however, the muscles were stronger at all time points than in B, with a DeltaP of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:DeltaP) and relaxation (-dP/dt:DeltaP) were significantly greater in group D than B. Protein analyses showed group D to have only a trend toward greater abundance of the fast isoforms of myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase (P>0.1). CONCLUSIOINS: ++Clen improves the performance of trained skeletal muscle in a model of aortomyoplasty by unknown mechanisms. These findings may have important implications in SMA.
Adrenergic beta-Agonists↗
Multiresolution restoration of medical signals using the renormalization group and the super-coupling transforms.
This paper presents a multiresolution approach to the restoration of Magnetoencephalographic (MEG) signals corrupted by colored Gaussian noise. We compare two methods, namely the renormalization group transform (RGT) and the super-coupling transform (ST). We conclude that although the RGT approach requires fewer site updates than the ST approach in order to converge, the ST approach is overall much faster. The multiresolution algorithm was tested with real and simulated data. In the case of simulated data, where the original signal's peak-to-peak value is known, the algorithm worked well with noise levels up to 80% of this value.
Algorithms↗
Transcervical cells and the prenatal diagnosis of haemoglobin (Hb) mutations.
Prenatal diagnoses of haemoglobin (Hb) mutations were performed using transcervical cells, retrieved by aspiration from the endocervical canal of ten selected pregnant women at about 10 weeks of gestation, prior to chorionic villus sampling (CVS). Both parents were carriers of haemoglobinopathies (thalassaemia or HbS). Clumps of fetal cells were isolated by micromanipulation under an inverted microscope and aliquots of the extracted DNA tested separately for the presence of paternally derived chromosome markers and Hb mutations by quantitative fluorescent polymerase chain reaction (PCR). The correct prenatal diagnosis of Hb diseases, using selected single clumps of trophoblastic cellular elements free of maternal contaminating cells, was achieved in six out of ten cases.
Anemia, Sickle Cell↗
Audit of prenatal diagnosis for hemoglobin disorders in the United Kingdom. The first twenty years.
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Anemia, Sickle Cell↗
Clenbuterol induces cardiac hypertrophy with normal functional, morphological and molecular features.
OBJECTIVE: Several pharmacological agents have been shown to produce 'physiological' or 'pathological' hypertrophy based on their functional characteristics. The aim of this study was to examine the features of cardiac hypertrophy induced by the selective beta 2-adrenergic agonist, clenbuterol. METHODS: Cardiac hypertrophy was induced in 7-week-old Sprague-Dawley rats by daily injections of clenbuterol for 3 weeks. Thyroxine and isoproterenol were also used to produce cardiac hypertrophy to serve as positive controls for physiological and pathological hypertrophy, respectively. Left ventricular function was determined using an isolated rat heart preparation. Ventricular samples were used for morphological examination while interstitial collagen was measured using high-pressure liquid chromatography. Expression of sarcoplasmic reticulum Ca(2+)-ATPase2a (SERCA2a) and phospholamban (PLB) were measured by dot blot analysis. RESULTS: Clenbuterol treatment induced 26% left ventricular hypertrophy. These hearts demonstrated normal systolic isovolumic parameters and diastolic (active relaxation and passive stiffness) function. In addition, left ventricular concentration of collagen and morphology was normal as were the expression of SERCA2a and PLB mRNA. CONCLUSION: These results suggest that clenbuterol-induced hypertrophy is 'physiological' in terms of its function, extracellular structure and gene expression.
Adenosine Triphosphatases↗
Assessment of diagnostic quantitative fluorescent multiplex polymerase chain reaction assays performed on single cells.
We have refined polymerase chain reaction (PCR) assays for the detection of sickle cell anaemia, the delta F 508 deletion causing cystic fibrosis, and the IVS1-110 mutation leading to beta thalassaemia, allowing them to be successfully performed upon single cells using fluorescent primers. We have also assessed the possibility of detecting aneuploidies of chromosomes 13, 18 and 21 using a quantitative fluorescent polymerase chain reaction (QF-PCR) with primers flanking polymorphic short tandem repeat (STR) markers. Trisomies were readily diagnosed by the detection of tri-allelic patterns. However some heterozygote normal and trisomic diallelic patterns did not produce the expected ratios of amplified PCR products due to preferential DNA sequence amplification. Total allelic drop out (ADO) did not occur with any of the cells tested. Multiplex QF-PCR assays can be performed on a single cell in under 6 h and simultaneously provide diagnosis of single gene defects, sex determination and an indication of selected chromosome aneuploidy.
Anemia, Hemolytic, Congenital↗
Pharmacological modulation of pressure-overload cardiac hypertrophy: changes in ventricular function, extracellular matrix, and gene expression.
BACKGROUND: Appropriate cardiac hypertrophy (CH) is necessary in several clinical settings, such as pulmonary artery banding in the two-stage arterial switch operation for transposition of the great arteries. Pressure-overload CH, however, produces ventricular dysfunction due to structural and molecular changes. The beta2-adrenergic receptor agonist clenbuterol has been shown to induce CH without such adverse effects to the rat heart. This study was performed to determine its effects on left ventricular (LV) function, structure, and gene expression in pressure-overload CH. METHODS AND RESULTS: Sprague-Dawley rats were assigned to one of four groups: 1, sham-operated (n=15); 2, banding of ascending aorta (n=22); 3, banding+clenbuterol (n=18); and 4, banding+thyroxine (n= 17). At the end of 3 weeks, groups 2, 3, and 4 showed an increase in LV mass index of 49.7+/-5.1%, 66.1+/-3.8%, and 47.6+/-4.6%, respectively, relative to group 1. A subgroup with severe CH (>50%) in group 2 was found to have significantly impaired developed pressure and diastolic relaxation and an increase in passive stiffness, with significantly reduced LV expression of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a) mRNA and increased LV collagen concentration. In comparison, similarly hypertrophied animals in groups 3 and 4 demonstrated improved developed pressure, normal relaxation and diastolic stiffness with normal collagen concentration, and a greater abundance of SERCA2a mRNA. CONCLUSIONS: Clenbuterol administration in conjunction with pressure overload produces a specific type of CH with preserved LV function. In addition, an increase in LV mass was associated with less fibrosis and greater expression of SERCA2a mRNA than banding alone.
Analysis of Variance↗