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1.
Hippokratia ; 26(2): 62-69, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37188045

RESUMO

BACKGROUND: Our study aimed to identify the total costs of inpatient treatment for coronavirus disease 2019 (COVID-19) in a tertiary institution in Serbia, an upper-middle-income country in Southeast Europe. METHODS: An observational, retrospective, cost-of-illness study was performed from the perspective of the National Health Insurance Fund and included a cohort of 78 females and 118 males admitted to the COVID-19 ward units of a tertiary center during the first wave of the pandemic. RESULTS: The median of the total costs in the non-survivors subgroup (n =43) was 3,279.16 Euros [interquartile range (IQR): 4,023.34; range: 355.20-9,909.61) which is higher than in the survivors (n =153) subgroup 747.10 Euros (IQR: 1,088.21; 46.71-3,265.91). The cut-off value of 156.46 Euros regarding the total costs per day was estimated to have 95.3 % sensitivity and 91.5 % specificity for predicting patients' dismal prognosis, with the area under the curve (AUC) of 0.968 (95 % confidence interval: 0.940-0.996, p <0.001). CONCLUSIONS: Direct medical inpatient treatment costs for COVID-19 represent a significant economic burden. The link between increased costs and an ultimate unfavorable outcome should be further explored.HIPPOKRATIA 2022, 26 (2):62-69.

2.
Appl Opt ; 60(31): H12-H19, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34807148

RESUMO

Results concerning the controllable ablation of nano-layered thin films (NLTF) by femtosecond laser pulses are presented. Investigated samples were titanium-aluminum bilayers, deposited on a silicon substrate, with the top titanium or aluminum layer of variable thickness on the surface. Irradiation was done in ambient air with single femtosecond laser pulses under standard laboratory conditions. The samples were analyzed by complementary methods of optical and scanning electron microscopy and optical profilometry, exhibiting laser-fluence-dependent ablative removal either of the top layer or the entire bilayer or even partial ablation of the underlying silicon substrate. The removal (spallation) threshold fluences for the topmost layer are scalable versus its thickness almost irrespectively of its material, being rather selective for the Ti-coated samples and much less selective for the Al-coated samples. The removal of the entire bilayers was found to be strongly influenced by electronic properties of the underlying metallic layer, dictating the NLTF-Si adhesion, heat conduction, and capacity in the NLTFs toward the NLTF-Si interface and beyond, as well as by their thermophysical characteristics, e.g., almost twice higher melting temperature and enthalpy for Ti. As a result, precise fs-laser machining of the entire NLTFs is pronounced and selective for the samples with the fusible Al at the low-adhesion Al-Si interfaces, compared with the incomplete NLTF removal from the high-adhesion and refractory Ti-Si interfaces.

3.
Clin Nutr ; 40(5): 2754-2761, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33933741

RESUMO

BACKGROUND & AIMS: Nutrition education is not well represented in the medical curriculum. The aim of this original paper was to describe the Nutrition Education in Medical Schools (NEMS) Project of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: On 19 January 2020, a meeting was held on this topic that was attended by 51 delegates (27 council members) from 34 countries, and 13 European University representatives. RESULTS: This article includes the contents of the meeting that concluded with the signing of the Manifesto for the Implementation of Nutrition Education in the Undergraduate Medical Curriculum. CONCLUSION: The meeting represented a significant step forward, moved towards implementation of nutrition education in medical education in general and in clinical practice in particular, in compliance with the aims of the ESPEN Nutrition Education Study Group (NESG).


Assuntos
Educação Médica/organização & administração , Ciências da Nutrição/educação , Faculdades de Medicina/organização & administração , Sociedades Científicas/organização & administração , Universidades/normas , Currículo , Educação de Graduação em Medicina , Europa (Continente) , Humanos
4.
Acta Endocrinol (Buchar) ; 13(1): 40-46, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31149146

RESUMO

CONTEXT: Clinical research suggests that vitamin D deficiency correlates with mental illnesses. OBJECTIVE: The aim was to prove that the patients from the psychiatric health care service in Serbia had higher vitamin D deficiency than patients from general practice. DESIGN: The study had a cross-sectional design. METHODS: The study included 47 patients aged 19 - 76 of both sexes with different mental disorders. We performed sample size calculation on available data for vitamin D deficiency in patients in health care facilities compared with the general population. The concentrations of vitamin D in serums were measured by HPLC (high performance/pressure liquid chromatography). RESULTS: The mean value of vitamin D (standard deviation) in the whole group of study subjects was 16.27(10.62) ng/mL; 68.1% of the patients had a deficiency of vitamin D (25(OH)D<20 ng/mL). The difference is statistically significant from expected proportion of people with vitamin D deficiency in general practice (p=0.040). Serum concentrations of 25(OH)D were significantly correlated with serum concentrations of phosphorus (ϱ=0.336, p=0.024) and sodium (ϱ=0.304, p=0.038). CONCLUSIONS: The patients of psychiatry health care had significantly higher frequency of vitamin D deficiency than expected. There is a significant association between serum levels of vitamin D, and phosphate and sodium.

5.
Balkan J Med Genet ; 19(1): 21-28, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27785404

RESUMO

The aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

6.
Bratisl Lek Listy ; 116(10): 591-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26531869

RESUMO

OBJECTIVES: The aim of this study was to investigate the role of the lactic acidosis, as an early predictor of significant consequences and/or a fatal outcome in term neonates after a perinatal asphyxia. BACKGROUND: Severe perinatal asphyxia can generate multiple organ dysfunction and neonatal mortality. METHODS: In routine clinical practice, after an admission to the Intensive Care Unit, lactate concentration was determined in capillary blood samples during the first one to six hours after birth in 55 term newborns with the post-asphyxial hypoxic-ischemic encephalopathy. The control group consisted of 36 healthy term neonates randomly selected in the maternity ward at the Gynecology and Obstetrics Clinic. RESULTS: Significantly higher concentrations of lactate (p 8.7 mmol/L with 80 % sensitivity and 82% specificity indicated the development of the hypoxic-ischemic encephalopathy stage II/III, while the lactate level>9.95 mmol/L was a predictor of death, with 75% sensitivity and 74.4% specificity. CONCLUSION: Determination of lactate concentrations in serum of term newborns associated with risk factors for the perinatal asphyxia is a useful tool in diagnosing metabolic disorders and ischemic damage, particularly severe clinical forms (Tab. 2, Fig. 3, Ref. 34).


Assuntos
Estado Terminal , Ácido Láctico/sangue , Síndrome do Desconforto Respiratório do Recém-Nascido/sangue , Biomarcadores/sangue , Feminino , Humanos , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Masculino , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Estudos Retrospectivos , Sérvia/epidemiologia
7.
Urol Int ; 80(4): 389-97, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18587250

RESUMO

OBJECTIVES: The main purpose of the study was to identify and quantify clinical variables which predisposed incorrect diagnosis based on ultrasonography (US) and computed tomography (CT) findings in the patients with suppurative renal infections. PATIENTS AND METHODS: A retrospective review of radiological records of patients at 3 tertiary Serbian clinics of urology from 1999 to January 2006 was conducted. The series consisted of 49 women and 26 men, mean age = 56.7 years, ranging from 21 to 78. All patients underwent US examinations. Forty-one patients had undergone CT examinations, on 42 renal units (1 bilateral perirenal infection). The patients were categorized into 4 groups according to the type of suppurative infection: (a) unilocular renal or perirenal abscesses; (b) with pyonephrosis only; (c) with multiple renal or pyonephrosis infections along with extension on perirenal space, and (d) emphysematous infections. RESULTS: Incorrect diagnosis based on US record only depended on the suppurative entity. In the presence of pyonephrosis only, the risk of incorrect diagnosis was reduced for 4 times [odds ratio (OR) = 0.25], and in presence of emphysematous infections the risk increased 19.5 times (OR = 19.49). Perinephric abscesses which were not seen on US were those associated with pyonephrosis, abscesses smaller than 6 cm and gas-forming abscesses. The diagnosis of abscesses considerably varied in the cases of unilocular purulent collections compared to complex purulent collections (chi(2) = 8.177, p = 0.004). Overall, the risk for incorrect diagnosis is about 14 times higher using US only (OR = 14.5), while CT reduced the risk of it for about 37 times (OR = 0.027). CONCLUSIONS: CT was much more reliable than US to correctly identify the pathological entity of renal suppuration. Guiding treatment on US findings only seems hazardous as omission of some pathological processes is very likely.


Assuntos
Abscesso/diagnóstico por imagem , Nefropatias/diagnóstico por imagem , Infecções Urinárias/complicações , Abscesso/etiologia , Adulto , Idoso , Análise de Variância , Erros de Diagnóstico , Estudos de Avaliação como Assunto , Feminino , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Probabilidade , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Supuração/diagnóstico por imagem , Supuração/etiologia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Doppler/métodos , Infecções Urinárias/diagnóstico
8.
Acta Chir Iugosl ; 53(4): 99-104, 2006.
Artigo em Sérvio | MEDLINE | ID: mdl-17688043

RESUMO

Digital video technologies are new and powerful tools with wide applications in orthopaedics. Already integral to several common medical devices, digital images can be used for case documentation and presentation as well for diagnostic and surgical patient care information. Digital technologies allow easy manipulation of photographic, video and graphic materials in ways that were impossible with conventional techniques. Educational presentation has been transformed by use of computers and digital projectors. Understanding the basic foundations of digital imaging technology is important for effectively creating digital images, videos and presentations. In this review, we are going to discuss some of the issues that are raised by digital imaging in orthopaedics, digital image processing, as well as, we are giving some recommendations for good quality of pre-, post- and intra-operative photographs in clinical use.


Assuntos
Ortopedia , Gravação em Vídeo , Humanos
9.
Methods Find Exp Clin Pharmacol ; 24(10): 661-8, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12616958

RESUMO

Although the contractile effects of glutamate and related excitatory amino acids on gut smooth muscle strips have been demonstrated, the mechanisms, and particularly the physiological importance of that action, remain unknown. In this study, glutamate, aspartate, AMPA, quisqualate, cis-ACPD and (2R,4R)-APDC evoked concentration-dependent contraction of isolated adult rat gastric fundus, with EC50 values of 210 microM, 150 microM, 20 microM, 33 microM, and 2.7 microM and 7.9 microM, respectively. L-SOP (0.1 microM-1.9 mM) did not change the basal tone of the preparations. The maximal contractions evoked by glutamate (20 mM) were 38.83% compared with those elicited by acetylcholine (20 microM). The glutamate-evoked contractions were not affected by atropine, verapamil and nicardipine, blocked by CNQX (0.01 microM), or potentiated by Mg2+ (0.01-100 microM), ketamine (0.01-100 microM) and DL-AP5 (0.1-100 microM), as well as L-trans-2,4-PDC (1-100 microM). Analysis of glutamate's action on rat rectum (EC50 = 44 microM) could only be carried out at the early stages, as half of the preparations were not affected by glutamate. Only 5 out of 26 human longitudinal and circular smooth muscle preparations taken from the stomach and three segments of the large intestine were very slightly contracted by glutamate, excluding further analysis. The contractile effects of glutamate on rat gut smooth muscles were mediated by multiple GluR (non-NMDA > NMDA > group I/II mGluRs) located primarily on smooth muscle cells but functional GluRs on neurons and/or nerve fibers of myenteric nervous plexuses could not be excluded. To fully understand the physiological significance of glutamate-evoked contractions in the gut, more research is required, most likely using many different methodological approaches.


Assuntos
Cicloleucina/análogos & derivados , Ácido Glutâmico/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Prolina/análogos & derivados , Idoso , Animais , Ácido Aspártico/antagonistas & inibidores , Ácido Aspártico/farmacologia , Cicloleucina/farmacologia , Potencial Evocado Motor/efeitos dos fármacos , Feminino , Fundo Gástrico/química , Fundo Gástrico/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Humanos , Técnicas In Vitro , Intestino Grosso/efeitos dos fármacos , Intestino Grosso/cirurgia , Masculino , Pessoa de Meia-Idade , Prolina/farmacologia , Ácido Quisquálico/farmacologia , Ratos , Receptores de Glutamato/metabolismo , Reto/química , Reto/efeitos dos fármacos , Estômago/química , Estômago/efeitos dos fármacos , Estômago/cirurgia
10.
Srp Arh Celok Lek ; 129 Suppl 1: 47-50, 2001.
Artigo em Sérvio | MEDLINE | ID: mdl-15637991

RESUMO

INTRODUCTION: Choledochal cyst, although a rare disease, is the most frequent malformation of the extrahepatic biliary ducts. The review of the world medical literature gives the overall number of 2500 cases of choledochal cyst. The incidence of this disease is about 1 in 2000000, but it is about four times more frequent in the Yellow race, and 3 times more frequent in females. Congenital choledochal cyst is a disease of paediatric population, as 60% of all patients are younger than 10 years. The basic anomaly of the disease is the embryological arrest of the normal migration of the pancreaticobiliary junction towards the duodenal wall. The result of the disturbance is the extraduodenal location of the pancreaticobiliary junction and the abnormally long common biliopancreatic channel. The flow of bile and pancreatic juice in the duodenal luminary space is insufficient, so the accumulation of bile and pancreatic juice in the common channel and the reflux of this activated mixture towards biliary ducts occur. Choledochal cyst is formed with all its complications: cholangitis, liver abscess, biliary stone formation, biliary cirrhosis, acute and chronic relapsing pancreatitis, and after many years, biliary cancer. Our results in the treatment of this disease are given. We operated on 31 paediatric patients for choledochal cyst over the period 1978-1998. The study is both retrospective and prospective. RESULTS: There were 24 girls and 7 boys, from neonates to teenagers. In 83 percent of patients the complaints started during the first 3 years of life. Unfortunately, only in 22% of patients the complaints were lasting less than 3 months untill the time of operation. The basic complaints were: abdominal pain and jaundice in 95% of patients, vomiting in 74%, high temperature and fever in 56% and palpabile tumour in 48%. About 30% of children had a relapsing cholangitis and 35% of patients an acute or chronic relapsing pancreatitis. Biliary stones were found in 18% of patients. High level of bilirubins was found in 52% of patients, serum transaminase (SGOT and SGPT) in 69%, amylase level was elevated in blood and urine in about half of the patients, and in choledochal cyst in 91%. Ultrasonography was carried out in 78% of patients and has proved to be a very good screening diagnostic tool. Endoscopic retrograde cholangiopancreaticography (ERCP) was performed in most of the patients. DISCUSSION: The only treatment of choledochal cyst is surgical. The conservative treatment is reserved only for complications (pancreatitis, cholangitis). The only adequate surgical treatment is the radical treatment, which consists of the resection of the whole anomalous choledochus and definitive separation of bile ducts from the pancreatic duct. This is achieved by the technique of Roux-en-Y hepaticojejunostomy. The paliative method of internal drainage of choledochal cyst consists of cystoduodeno or cystojejunostomy, but is now abandoned, as the disease continues with all its manifestations and complications. The internal drainage was performed in 6 our patients, but one of them died (a neonate with sepsis at admitance). Three patients were excluded from the study, and 2 girls were later radically reoperated on. In all other 25 patients resection of the whole choledohus and Roux-Y hepaticojejunostomy were carried out. There were neither operative, nor postoperative deaths. Except the temporary bile leaking, spontaneously healed, there were no significant intraoperative complications. All patients were regularly followed-up, they had no complaints, and all their laboratory and ultrasonographic findings were normal. CONCLUSION: Congenital dilatation of biliary ducts is a rare disease, but it must be considered in differential diagnosis of unclear upper abdominal pains, jaundice and pancreatitis in children. In the diagnosis of this disease the ultrasound imaging is of utmost importance as a screening method, and endoscopic retrograde cholangio-pancreaticography as a method of complete visualization. Resection of the diseased common bile duct and Roux-Y hepatico-jejunostomy are the method of choice in the treatment of children with choledochal cyst.


Assuntos
Cisto do Colédoco , Adolescente , Criança , Pré-Escolar , Cisto do Colédoco/diagnóstico , Cisto do Colédoco/cirurgia , Feminino , Humanos , Lactente , Masculino
11.
Srp Arh Celok Lek ; 128(5-6): 191-3, 2000.
Artigo em Sérvio | MEDLINE | ID: mdl-11089420

RESUMO

The paper deals with the advantages of ultrasound diagnosis of hypertrophic pyloric stenosis in newborns. Ultrasound decreases the number of radiological examinations of gastroduodenum and reduces diagnostic exposure of children to X-rays. In the last three years 107 children had manifested clinical signs of hypertrophic pyloric stenosis. The ultrasound studies revealed hypertrophic pyloric stenosis in 55 patients (51.4%). There were 48 boys (87.3%) and 7 girls (12.7%). Patients were aged 17 to 75 days (average about 40 days). The sonogram finding was typical for hypertrophic pylorus, which made the diagnosis easier. There were no false positive or false negative ultrasound findings. All patients with hypertrophic pyloric stenosis were operated on and diagnosis was confirmed. Ultrasound is reliable in diagnosis of hypertrophic pyloric stenosis. Ultrasound examination is technically easy and fast, what is important for urgent surgical therapy. In children with persistent projectile vomiting, suspected of hypertrophic pyloric stenosis, ultrasound is the method of choice and should replace X-ray examinations.


Assuntos
Estenose Pilórica/diagnóstico por imagem , Feminino , Humanos , Hipertrofia , Lactente , Recém-Nascido , Masculino , Ultrassonografia
12.
Int J Med Inform ; 58-59: 29-37, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10978907

RESUMO

Many diagnostic and therapeutic procedures depend on medical images. In order to overcome imperfections of the obtained images, which are due to the acquisition process, and to extract new information from the available images, many techniques have been developed. In this study, a new method of image segmentation and 3D reconstruction based on active contour models ('snakes') was applied in analyzing computed tomography (CT) images in patients with acute head trauma. Using this method, lesion to brain (LBR) and ventricle to brain ratio (VBR) parameters, as well as 3D reconstruction of traumatic lesion, was obtained accurately. In our study group, 215 patients (mean age 42.4+/-23.5 years, 138/215 (64.2%) males) were included. Among them, 72 (33.5%) did not survive during hospitalisation in the Emergency Department. LBR correlated with the Glasgow Coma Score and the intrahospital outcome (r=-0.457 and r=0.515, respectively). Besides, non-survivors had greater LTB values (0.042+/-0.034) than survivors (0.005+/-0.011). However, VBR did not correlate with these clinical parameters. In addition, LBR was significantly higher in the patients with other pathologic CT findings. The proposed methodology, based on extracting maximum information from available CT scans, could be a basis for further medical decision making in patients with acute head trauma.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Adulto , Artefatos , Ventrículos Cerebrais/patologia , Ventriculografia Cerebral , Técnicas de Apoio para a Decisão , Feminino , Humanos , Imageamento Tridimensional , Masculino
13.
Srp Arh Celok Lek ; 128(3-4): 97-103, 2000.
Artigo em Sérvio | MEDLINE | ID: mdl-10932618

RESUMO

INTRODUCTION: The Hartnup mutation affects the amino acid transport system of the intestine and kidney used by a large group of neutral amino acids (monoamino-monocarboxylic acids) resulting in a characteristic pattern of neutral aminoaciduria [2, 5, 6]. METHODS AND PATIENTS: In this research clinical and neurological methods and a great number of laboratory tests were used. Patient 1. A 16-year-old girl, born in 1972, was a full-term newborn. Her psychomotor development was normal. She is the eldest of three children in the family. Till the age of 10 the girl was healthy, except for the mild skin disorders on uncovered parts of the body, face and hands, occurring in springtime almost every year. She had had two exacerbations of the disease. The first exacerbation lasted between the end of April and August 22, 1982. The second began in the middle of November 1987 and finished on May 31, 1988. A changeable and severe clinical feature in this girl was characterized by polymorphic, transient mainly cerebral symptoms, papilloedema with peripapillary haemorrhage and pellagra-like skin rash. At the beginning of the disease the left spastic haemiplegia with bilateral Babinski's reflex and diffuse brain oedema were observed. Signs of the upper motor neurone lesion and myoclonic jerks of limbs and face were most persistent during the first and second exacerbation of the disease. Dysinhibition phenomenon: mandibular, snout and palmomental reflexes were sometimes positive. Mental states at the time of hospitalization were changed and characterized by bradypsychic, torpid, disoriented in time and confused at the beginning of the disease. She had severe psychotic episodes during the second relapse of the disease. The symptoms and signs of the disease as well as pellagra-like skin rash resolved with nicotinamide therapy. Patient 2. A 38-year-old man; clinically healthy, with no skin lesions. A gross aminoaciduria was found in this case. However, the amino acids pattern was atypical. DISCUSSION: This new, rare disease was described [1] with complex and variable clinical symptoms, intermittent course, permanent aminoaciduria and other biochemical features. In our symptomatic patient diagnosis of Hartnup disease was established during the second exacerbation of the disease. CONCLUSION: Two cases of Hartnup disease, one symptomatic and one asymptomatic, were diagnosed in a five member family. A child in this family died at the age of 3.5 probably from Hartnup disease.


Assuntos
Doença de Hartnup/diagnóstico , Adolescente , Adulto , Feminino , Doença de Hartnup/genética , Humanos , Masculino
14.
Pharmacogenomics ; 1(2): 187-97, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-11256590

RESUMO

RNA splicing is a tightly regulated process. It is essential for gene expression and, therefore, intervenes in every biological phenomenon in mammals. RNA splicing regulation is cell type-specific in such a way that a cellular situation can be characterised by its repertoire of spliced events, the spliceome. Comparison of the splicing repertoire of two situations identifies alternative exons and introns. This regulation involves cis-acting sequences and transacting factors. Mutations, as well as modifications of signalling pathways, can alter the accuracy of splicing. Since deletion of exons or retention of introns within coding sequences modifies the corresponding proteins and functional domains of proteins are encoded by contiguous exons, identifying changes in the spliceome pinpoints functional domains, which are specifically regulated at the level of RNA splicing. We have developed a new method of gene profiling, qualitative gene profiling, that allows the comparative study of the repertoires of spliced events that characterise distinct physiopathological situations. We present in this review the different uses of this new genomic technique that can help each step of the R&D process in the pharmaceutical industry, and that represents a short cut towards functional genomics and pharmacogenomics.


Assuntos
Biologia Molecular/métodos , Farmacogenética/métodos , RNA Mensageiro/genética , Animais , Humanos , Isoformas de Proteínas , Splicing de RNA , RNA Mensageiro/química
15.
Pharmacol Res ; 39(2): 143-8, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10072705

RESUMO

Glutamate and aspartate are excitatory neurotransmitters in both central and peripheral nervous systems, acting on ionotropic and metabotropic receptors. In our study we have examined the effects of glutamate, aspartate, N-methyl-d-aspartate (NMDA), kainic acid and (+/-)-1-aminocyclopentane-cis-1,3-dicarboxylic acid (ACPD) on tone and spontaneous activity of isolated rat gastric fundus, jejunum, ileum, ascending colon and rectum. Both glutamate and aspartate produced concentration-dependent tonic contractions of rat fundus and rectum; the other gut segments used in the study were not responsive. While only NMDA and kainic acid produced concentration-dependent tonic contractions of isolated rat gastric fundus, all three type-selective agonists of glutamate receptors (NMDA, kainic acid and ACPD) produced tonic contractions of isolated rat rectum. The results of our study suggest that glutamate and aspartate in rat gastric fundus activate excitatory intrinsic neurons through only ionotropic receptors (NMDA and non-NMDA receptors), while the same action in rat rectum is mediated through both ionotropic and metabotropic receptors.


Assuntos
Sistema Digestório/efeitos dos fármacos , Aminoácidos Excitatórios/farmacologia , Animais , Ácido Aspártico/farmacologia , Cicloleucina/análogos & derivados , Cicloleucina/farmacologia , Sistema Digestório/anatomia & histologia , Fenômenos Fisiológicos do Sistema Digestório , Agonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ácido Glutâmico/farmacologia , Técnicas In Vitro , Ácido Caínico/farmacologia , Masculino , Contração Muscular/efeitos dos fármacos , Tono Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , N-Metilaspartato/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos , Receptores de Glutamato Metabotrópico/agonistas , Receptores de N-Metil-D-Aspartato/agonistas
16.
Croat Med J ; 40(1): 67-70, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9933898

RESUMO

Calculation of the pA2 value and dissociation constants for an antagonist from the effects observed on isolated smooth muscles can be done in two ways: using Schild's plot procedure or Schild's equation. In our study we used the effects of muscarinic antagonists observed in experiments on isolated human and feline stomach and rat gastric fundus. Only the estimates of pA2 values and dissociation constants made using the Schild's equation on the basis of the lowest antagonist concentrations were not significantly different from the values calculated using the Schild's plot procedure. This suggest that, when it is impractical to perform the full Schild's plot procedure, the best estimate of pA2 values and dissociation constants can be done with the lowest antagonist concentration that significantly inhibits the effects of an agonist on an isolated smooth muscle preparation.


Assuntos
Antagonistas Muscarínicos/farmacologia , Músculo Liso/efeitos dos fármacos , Animais , Gatos , Humanos , Ratos
17.
Adv Exp Med Biol ; 467: 191-7, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10721056

RESUMO

Each headache can be a complex diagnostic, therapeutic, prognostic and social problem. The pain in the head can be connected with many organic and non-organic causes. In this work, the levels of plasma and urinary free 5-HT and 5-HIAA were investigated in eight migraine (aged 23-59 years) and ten tension-type headache suffers (aged 38-61 years). Based on the data obtained and their correlation with clinical features and in comparison with a control group, the following can be stated: (1) there is involvement of serotonin in migraine and tension-type headache during the attacks, although the positive 5-HT values from plasma were small; (2) urinary 5-HT values in migraine and tension-type headache were normal in comparison to the control group; (3) significantly decreased values of 5-HIAA in urine were found both in migraine and tension-type headache groups. These findings show that catabolism of 5-HT is probably decreased during headache periods; (4) visual aura was found in five out of ten subjects with tension-type headache.


Assuntos
Ácido Hidroxi-Indolacético/sangue , Transtornos de Enxaqueca/sangue , Serotonina/sangue , Cefaleia do Tipo Tensional/sangue , Adulto , Idade de Início , Eletroencefalografia , Feminino , Humanos , Ácido Hidroxi-Indolacético/urina , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/fisiopatologia , Transtornos de Enxaqueca/urina , Valores de Referência , Serotonina/urina , Cefaleia do Tipo Tensional/fisiopatologia , Cefaleia do Tipo Tensional/urina
18.
Adv Exp Med Biol ; 467: 289-95, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10721068

RESUMO

In this work clinical and biochemical findings are presented in three untreated children with phenylketonuria in a family. Their clinical pictures were not typical for classical phenylketonuria. As a result, diagnosis was missed. It has been shown that patterns of large neutral amino acids in serum and urine were somewhat different. Significantly lower serum TRP/LNAA ratio was observed in all patients with phenylketonuria, compared to the control group. These findings suggest that there was subnormal tryptophan availability in the central nervous system leading to its decreased metabolism through the serotonin and kynurenine pathways. These results may explain decreased children's growth and their mental deficiency.


Assuntos
Aminoácidos/sangue , Fenilcetonúrias/sangue , Fenilcetonúrias/genética , Triptofano/sangue , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Linhagem , Fenilcetonúrias/urina , Valores de Referência , Triptofano/urina
19.
Adv Exp Med Biol ; 467: 297-302, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10721069

RESUMO

Alteration of monoamine levels by some antiepileptic drugs (AEDs) was elucidated in this study. Lamotrigine (LTG) is a new AED, acting the sodium-channels. LTG was given as add-on therapy to 16 patients aged 4.5-18 yrs with intractable epilepsy and comedicated with carbamazepine or valproate. An equal group of epileptics with comparable clinical characteristics and treatment served as control. Plasma and urinary (24 h-samples) serotonin and 5-HIAA were determined before onset of LTG therapy and after 2-3 months. HPLC and electrochemical detection was used for the determination of serotonin (5-HT) and 5-hydroxy indoleacetic acid (5-HIAA). No significant effect of LTG on both urinary 5-HT and 5-HIAA levels was found, whereas plasma 5-HT concentrations significantly decreased in comparison with levels before LTG starting and relevant values in controls. This findings was noted in 7/16 children with favourable response to LTG. Increased serotonin catabolism may be result of LTG action.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Ácido Hidroxi-Indolacético/sangue , Serotonina/sangue , Triazinas/uso terapêutico , Adolescente , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Epilepsia/urina , Feminino , Humanos , Ácido Hidroxi-Indolacético/urina , Lamotrigina , Masculino , Serotonina/urina , Ácido Valproico/uso terapêutico
20.
Stud Health Technol Inform ; 68: 395-9, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10724914

RESUMO

Many diagnostic and therapeutic procedures depend on medical images. In order to overcome imperfections of obtained images which are due to acquisition process and to obtain new information from available images, many techniques have been developed. In this study relatively new method of image segmentation, active contour model--"snakes" was applied in analyzing computed tomography (CT) images in patients with acute head trauma. Using this method, lesion to brain (LBR) and ventricle to brain ratio (VBR) were obtained accurately. Quantitative variable LBR, is significantly higher in patients with other pathologic CT findings and who do not survive during hospitalization. Thus, by applying segmentation "snakes" model it is possible to extract maximum information from available CT scans. These variables could be basis for medical decision making in patients with acute head trauma.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Artefatos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Ventrículos Cerebrais/patologia , Ventriculografia Cerebral , Técnicas de Apoio para a Decisão , Humanos
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