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Biomedical subjects

J Leal

Publications and source records attributed to J Leal.

At least 19 recordsLinked to original sources
PubMed2006

Cost of cardiovascular diseases in the United Kingdom.

OBJECTIVE: To estimate the economic burden of cardiovascular disease (CVD) in the United Kingdom, including health and non-healthcare costs, and the proportion of total CVD cost due to coronary heart disease (CHD) and cerebrovascular disease. DESIGN AND SETTING: Prevalence-based approach to assess CVD-related costs from a societal perspective. PATIENTS: All UK residents in 2004 with CVD (International classification of diseases, 10th revision (ICD-10) codes I00-I99) and subgroups with CHD (ICD-10 codes I20-I25) or cerebrovascular disease (ICD-10 codes I60-I69). MAIN OUTCOME MEASURES: Healthcare costs were estimated from expenditure on community health and social services, accident and emergency care, hospital care, rehabilitation and drugs. Non-healthcare costs were estimated from data on informal care and from productivity losses arising from morbidity and premature death. RESULTS: CVD cost the UK economy 29.1 billion pound in 2004, with CHD and cerebrovascular disease accounting for 29% (8.5 billion pound) and 27% (8.0 billion pound) of the total, respectively. The major cost component of CVD was health care, which accounted for 60% of the cost, followed by productivity losses due to mortality and morbidity, accounting for 23%, with the remaining 17% due to informal care-related costs. CONCLUSIONS: CVD is a leading public health problem in the UK measured by the economic burden of disease. This study identified the size and main components of that burden, and will help to inform decisions about research priorities and to monitor the impact of policy initiatives.

Absenteeism↗
PubMed2004

[Nonthermal levels of electric currents applied in capacitive electric transfer therapy provokes partial cytotoxic effects in human neuroblastoma cultures].

The present study investigates the cellular response to weak, sine wave, 0.5-MHz electric currents. The experimental exposure to identical signals at an intensity high enough as to significantly increase the temperature in target tissues, has provided positive responses in clinical treatments of tumors with capacitive electric transfer (CET) thermal therapy. The present results show that the in vitro exposure to CET signals at athermal doses causes cytotoxic effects in human neuroblastoma cells. Such a response seems to be due to signal-induced alterations in the cell cycle. As a whole, the results suggest that the potential therapeutic effects of the CET strategy could be due to the thermal response of the tissues to the currents, added to an athermal response of the cells to the electric current itself.

Cell Division↗
PubMed2004

Co-existence of anemia, vitamin A deficiency and growth retardation among children 24-84 months old in Maracaibo, Venezuela.

Iron deficiency anemia has been associated with alterations in child development and psychomotor function, being myelination and dopaminergic functioning especially vulnerable. Iron deficiency, at different ages, has different reversible and irreversible effects on CNS. Anemia has also been related to vitamin A deficiency (VAD) and growth retardation. The aim of the present paper was to determine the coexistence of micronutrient deficiency, iron and vitamin A, and macronutrient deficiency (growth retardation). The sample consisted of 202 Venezuelan children, aged 24-84 month old, (104 girls, 98 boys); Anemia, VAD and growth retardation was evaluated by means of blood hemoglobin concentration analysis, HPLC serum retinol (values <20 microg/dl reveal VAD) and height/age and weight/age Z scores (< or = - 2 SD express stunting and underweight). Prevalence of anemia was 38.11%; VAD, 21.78%; stunting, 14.36% and underweight, 9.40%. Anemia and VAD clustered in 7.92%; anemia + stunting or + underweight coexisted in 5.94% and 2.97%, respectively. Stunting and underweight clustered with VAD in 2.97% and 1.48%. The three-way combination with anemia was only seen with stunting in 0.99% of the sample. The prevalence of micronutrient deficiencies remain as significant public health problems which should be simultaneously treated as virtually independent, giving priority to infant, toddler and preschool age groups.

Anemia↗
PubMed2000

Inhibition of farnesyltransferase with A-176120, a novel and potent farnesyl pyrophosphate analogue.

Farnesylation of Ras is required for its transforming activity in human cancer and the reaction is catalysed by the enzyme farnesyltransferase. Recently, we discovered a novel chemical series of potent farnesyl pyrophosphate (FPP) analogues which selectively inhibited farnesyltransferase. Our most potent compound to date in this series, A-176120, selectively inhibited farnesyltransferase activity (IC(50) 1.2+/-0.3 nM) over the closely related enzymes geranylgeranyltransferase I (GGTaseI) (IC(50) 423+/-1.8 nM), geranylgeranyltransferase II (GGTaseII) (IC(50) 3000 nM) and squalene synthase (SSase) (IC(50)>10000 nM). A-176120 inhibited ras processing in H-ras-transformed NIH3T3 cells and HCT116 K-ras-mutated cells (ED(50) 1.6 and 0.5 microM, respectively). The anti-angiogenic potential of A-176120 was demonstrated by a decrease in Ras processing, cell proliferation and capillary structure formation of human umbilical vein endothelial cells (HUVEC), and a decrease in the secretion of vascular endothelial growth factor (VEGF) from HCT116 cells. In vivo, A-176120 reduced H-ras NIH3T3 tumour growth and extended the lifespan of nude mice inoculated with H- or K-ras-transformed NIH3T3 cells. A-176120 also had an additive effect in combination with cyclophosphamide in nude mice inoculated with K-ras NIH3T3 transformed cells. Overall, our results demonstrate that A-176120 is a potent FPP mimetic with both antitumour and anti-angiogenic properties.

Alkyl and Aryl Transferases↗
PubMed2000

Two-chain high molecular weight kininogen induces endothelial cell apoptosis and inhibits angiogenesis: partial activity within domain 5.

We previously reported that the binding of two-chain high molecular weight kininogen (HKa) to endothelial cells may occur through interactions with endothelial urokinase receptors. Since the binding of urokinase to urokinase receptors activates signaling responses and may stimulate mitogenesis, we assessed the effect of HKa binding on endothelial cell proliferation. Unexpectedly, HKa inhibited proliferation in response to several growth factors, with 50% inhibition caused by approximately 10 nM HKa. This activity was Zn(2+) dependent and not shared by either single-chain high molecular weight kininogen (HK) or low molecular weight kininogen. HKa selectively inhibited the proliferation of human umbilical vein and dermal microvascular endothelial cells, but did not affect that of umbilical vein or human aortic smooth muscle cells, trophoblasts, fibroblasts, or carcinoma cells. Inhibition of endothelial proliferation by HKa was associated with endothelial cell apoptosis and unaffected by antibodies that block the binding of HK or HKa to any of their known endothelial receptors. Recombinant HK domain 5 displayed activity similar to that of HKa. In vivo, HKa inhibited neovascularization of subcutaneously implanted Matrigel plugs, as well as rat corneal angiogenesis. These results demonstrate that HKa is a novel inhibitor of angiogenesis, whose activity is dependent on the unique conformation of the two-chain molecule.

Amino Acid Sequence↗
PubMed1999

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Alkyl and Aryl Transferases↗
PubMed1997

[Importance of nutritional aspects in attention deficit hyperactivity disorders].

The attention deficit hyperactivity disorder is a common childhood syndrome that is recognized as an important medical-social problem, being the object of an exhaustive investigation related to its etiology, diagnostic approach and prevention, and treatment forms. Among the factors that can alter the cerebral function, is the malnutrition. The authors discuss the association of the syndrome with the nutritional condition of students from elementary schools.

Analysis of Variance↗
PubMed1997

[Clinical significance of episodes of apnea in babies].

INTRODUCTION: The presence of episodes of apnea (EA) in infants is very alarming and requires rapid, precise determination of the etiology in view of the relationship with the syndrome of sudden death of infants. MATERIAL AND METHODS: We therefore studied 16 patients, aged between 1 and 12 months, admitted to to hospital after having episodes where they stopped breathing for more than 15 seconds, with or without associated bradycardia. Patients with previous or associated convulsions, premature birth or low birth weight for gestational age were excluded from the study. In all cases a prolonged EEG was recorded. RESULTS: The commonest age of presentation of EA was 3-4 months. In one case there was a history of a sudden infant death occurring in a brother. The etiology was determined in 12 cases: gastroesophageal reflex in 5, epilepsy in 3, hyponatremia in 2, drug reaction in 1, bronchiolitis in 1 and hypoglycemia in another. In three cases where no cause was found the EA was not repeated, although apnea monitorization was necessary for several months because of the anxiety of the family. CONCLUSIONS: Of the 3 cases in which EA was a critical epileptic sign, only 2 could be demonstrated on a Holter recording. In one of these, progress was poor and resistant crises of different morphology later occurred. We consider that EA in infants requires a thorough etiological study. Cases of unknown etiology require prolonged EEG recording to determine whether the apnea is cerebral in origin, followed by prolonged monitorization of apneas to avoid possible sudden death.

Apnea↗
PubMed1997

The value of Hughes-Cardiff classification in the management of perianal Crohn's disease.

PURPOSE: The aim of this study was to assess the value of Hughes' pathogenic classification in the prognosis and management of perianal Crohn's disease (CD). PATIENTS AND METHODS: This classification differentiates between purely inflammatory lesions and their mechanical or septic complications, and defines the presence of ulceration (U), fistula (F) and stricture (S), which are assigned a score of 0, 1 or 2 according to the severity and associated conditions, proximal intestinal involvement and disease activity (A, P and D). Of a series of 96 patients with CD, 12 underwent 16 procedures involving anesthesia to treat symptomatic anal lesions. Patients presenting with severe pain were explored and treated by surgical drainage or, in cases in which there was no demonstrable sepsis, by gentle dilation or infiltration with steroids. For superficial, non-specific fistulas, conventional fistulotomy was performed, and long-term seton drainage was implanted for complex fistulas. Strictures were treated by gentle dilation. Uncontrolled sepsis or proctocolitis was managed by proximal stoma creation or proctocolectomy. RESULTS: The association of cavitating ulcers (U2) and contiguous active rectal involvement (P1) was a contraindication for rectal preservation, making proctectomy or stoma creation the most feasible therapeutic option. The etiology of most, but not all, complex fistulas (F2) was the progressive cavitation of U2, whilst F1 was either of cryptoglandular origin or the result of epithelialized fissures (U1). The treatment was also adjusted to this association, and it was confirmed that most of the severe lesions (F2) and S2) were secondary to U2. CONCLUSIONS: Hughes' pathogenic classification: 1) makes it possible to set up an easily stored registry of anal and perianal Crohn's disease; 2) identifies predefined lesions, allowing the individualization of therapeutic procedures and the comparison of results, and 3) provides prognostic information.

Adolescent↗
PubMed1994

Schinzel-Giedion syndrome: autopsy report and additional clinical manifestations.

Schinzel-Giedion syndrome (SGS) is a rare and incompletely defined condition. This is the third postmortem study on a boy with SGS and other unusual findings. He had a primitive neuroectodermal tumor in the lumbosacral region, bilateral syndactyly of hands and feet, and brain anomalies in addition to the major manifestations of the syndrome. We consider these clinical findings as possible additional manifestations of the syndrome since, of 19 SGS patients reported, 4 had syndactyly and 3 had embryonal tumors. In addition, the 3 published necropsy studies report brain anomalies. Knowledge that these changes occur in SGS may help facilitate diagnosis and improve our understanding of the syndrome.

Abnormalities, Multiple↗
PubMed1994

Chick embryo development can be irreversibly altered by early exposure to weak extremely-low-frequency magnetic fields.

Several reports have shown that weak, extremely-low-frequency (ELF), pulsed magnetic fields (PMFs) can adversely affect the early embryonic development of the chick. In this study, freshly fertilized chicken eggs were exposed during the first 48 h of postlaying incubation to PMFs with 100 Hz repetition rate, 1.0 microT peak-to-peak amplitude, and 500 microseconds pulse duration. Two different pulse waveforms were used, having rise and fall times of 85 microseconds (PMF-A) or 2.1 microseconds (PMF-B). It has been reported that, with 2 day exposure, these fields significantly increase the proportion of developmental abnormalities. In the present study, following exposure, the eggs were allowed to incubate for an additional 9 days in the absence of the PMFs. The embryos were taken out of the eggs and studied blind. Each of the two PMF-exposed groups showed an excess in the percentage of developmental anomalies compared with the respective sham-exposed samples. This excess of anomalies was not significant for the PMF-A-treated embryos (P = 0.173), whereas it was significant for the PMF-B-exposed group (P = 0.007), which showed a particularly high rate of early embryonic death. These results reveal that PMFs can induce irreversible developmental alterations and confirm that the pulse waveform can be a determinant factor in the embryonic response to ELF magnetic fields. The data also validate previous work based on the study of PMFs' effects at day 2 of embryonic development under field exposure.

Abnormalities, Radiation-Induced↗
PubMed1994

Genotoxic and mutagenic effects of guarana (Paullinia cupana) in prokaryotic organisms.

Aqueous extracts of Paullinia cupana (guarana), a species that belongs to the Sapindaceae family, were analyzed for the presence of genotoxic activities in bacterial cells. The extracts of guarana were genotoxic as assessed by lysogenic induction in Escherichia coli and they were also able to induce mutagenesis in Salmonella typhimurium. Addition of S9 microsomal fraction, catalase, superoxide dismutase or thiourea counteracted the genotoxic activity of guarana, suggesting that oxygen reactive species play an essential role in the genotoxicity of aqueous guarana extracts. The genotoxic activity in the extracts was related to the presence of a molecular complex formed by caffeine and a flavonoid (catechin or epicatechin) in the presence of potassium.

Caffeine↗