Tratamiento de heridas complejas mediante fibrina rica en plaquetas y leucocitos (L-PRF), experiencia inicial de un centro / Treatment of complex wounds using platelet rich fibrin and leukocytes (L-PRF), initial experience of a center

Resumen Introducción El uso de concentrados plaquetarios para el tratamiento de heridas complejas y regeneración tisular está siendo ampliamente utilizado a nivel mundial. Durante el último tiempo, la segunda generación de concentrados plaquetarios, particularmente el L-PRF, ha permitido tratar de manera efectiva a pacientes con esta patología. Debido a su bajo costo y versatilidad, ha sido posible aplicar esta técnica en variadas situaciones clínicas con buenos resultados. El objetivo de este trabajo es presentar nuestra experiencia utilizando L-PRF para la curación de heridas complejas (CHC) como una alternativa al uso de injertos de distinto grado de complejidad. Materiales y Método: Se realizó un análisis prospectivo de una serie de casos de pacientes que fueron sometidos a tratamiento quirúrgico de heridas complejas mediante el uso de L-PRF en el Hospital Santiago Oriente - Luis Tisné Brousse, entre los meses de enero de 2017 y diciembre de 2018. Mediante examen clínico y parámetros de inclusión, de éxito y de fracaso definidos previamente, se evaluó un total de 11 pacientes con heridas complejas a los cuales se les realizó un tratamiento local con injerto de L-PRF. Resultados: _La etiología de las heridas fue variada. 8 (72%) de los casos lograron una epitelización del 100% y 3 (28%) fracasaron. Se identificaron factores predisponentes para el fracaso de la técnica, y también fue posible establecer una relación de predicción de éxito en donde se relaciona una probabilidad alta de epitelización cuando la granulación de la herida ocurre durante los primeros 10 días sobre el injerto de L-PRF. Conclusión: El tratamiento de heridas complejas mediante L-PRF es una alternativa factible, de bajo costo y requerimientos (comparada con el uso de injertos, colgajos y sustitutos dérmicos), es segura en la resolución de heridas complejas, permitiendo disminuir la morbilidad, los costos asociados al tratamiento y estadía hospitalaria.

Introduction: The use of platelet concentrates for the treatment of complex wounds and tissue regenera-tion is being widely used worldwide. During the last time, the second generation of platelet concentrates, particularly L-PRF, has made it possible to effectively treat patients with this pathology. Due to its low cost and versatility, it has been possible to apply this technique in various clinical situations with good results. The objective of this work is to present our experience using L-PRF for the healing of complex wounds (HCC) as an alternative to the use of grafts of different degrees of complexity. Materials and Method: A prospective analysis was carried out with a series of cases who underwent surgical treatment of complex wounds using L-PRF at Santiago Oriente - Luis Tisné Brousse Hospital, between the months of January 2017 and December 2018. Through clinical examination and previously defined inclusion, success, and failure parameters, a total of 11 patients with complex wounds were evaluated who underwent local treatment with an L-PRF graft. Results: The etiology of the wounds was varied. 8 (72%) of the cases achieved 100% epithelialization and 3 (28%) failed. Predisposing factors for the failure of the technique were identified, and it was also possible to establish a predictive relationship of success where a high probability of epithelialization is related when the granulation of the wound occurs during the first 10 days on the L-PRF graft. Conclusion: The treatment of complex wounds using L-PRF is a feasible alternative, with low cost and requirements (compared to the use of grafts, flaps and dermal substitutes) and safe in the resolution of complex wounds, allowing to reduce morbidity, the costs associated with treatment and hospital stay.

Colgajos Locales en Reconstrucción Facial. Alternativas de Tratamiento

RESUMEN: Los defectos faciales de piel son frecuentemente secuelas producto de carcinomas basoceulares, carcinomas espinocelulares, melanomas, grandes tumores benignos o traumatismos de tejidos blandos. Las unidades y subunidades estéticas de la cara, la textura y color de la piel, junto a otros parámetros deben ser considerados durante la planificación de la reconstrucción mediante colgajos locales. El objetivo de este artículo de revisión bibliográfica fue describir y definir las técnicas más relevantes en los de colgajos locales aplicados en la reconstrucción facial y sus algoritmos actuales, en relación con la unidad o subunidad facial involucrada; sus consideraciones estéticas y cirugía complementaria. Las unidades y subunidades estéticas de la cara se dividen en regiones de la frente, párpados, mejillas, nariz, labios y mentón. Los colgajos de rotación, en isla, de avance y transposición son la base para la mayoría de los colgajos faciales; los más conocidos según la zona donante son: el colgajo frontal, colgajo de rotación y avance de mejilla; colgajo cérvico-facial, y colgajos nasolabiales, entre otros. La elección del colgajo depende de la zona y la unidad estética facial involucrada, siendo importante elegir y usar las líneas, los surcos y márgenes de estas unidades cuando sea posible con el fin de mejorar los resultados estéticos y reducir la posibilidad de secuelas. La cirugía complementaria y los procedimientos estéticos pueden lograr un buen camuflaje de algunas complicaciones estéticas o secuelas.

ABSTRACT: Skin face defects are frequently sequels of basal cell carcinomas, squamous cell carcinomas, melanomas, and large benign tumors or soft tissue trauma. Aesthetics units and subunits of the face, texture, color, and other parameters must be considered in the local flaps reconstructive planning. This review article aims to describe and define the most relevant techniques of facial local flaps in facial reconstruction and their current algorithms, regarding the unit or subunit, involve, their aesthetics considerations and complementary surgery. The aesthetics units and subunits of the face are divided into forehead, eyelids, cheek, nasal, lips, and chin. There are several well-known concepts and flaps used in these proceedings as rotation, island, advancement, and transposition flaps, and they are the basis for facial local flaps; The most relevant are: forehead flap, cheek advancement, and rotate flap; rhomboid, cervicofacial and bilobed flap, nasolabial flaps. The flap election depends on the zone and unit involve; it is important to choose the lines, sulcus, and borders of these units when is possible to enhance these aesthetics outcomes. These concerning improve the aesthetics outcomes and reduce the aesthetics sequels. Complementary surgery and aesthetics proceedings may accomplish a good camouflage of some aesthetics complications or sequels.

A comparison of secondary prevention practice in poststroke and coronary heart disease patients.

OBJECTIVES: It is evident that patients with atherosclerotic vascular disease (AVD) benefit from appropriate secondary prevention. In clinical reality, the secondary prevention in AVD patients other than those with coronary heart disease (CHD) is often overlooked. Therefore, we compared the adherence to secondary prevention principles between poststroke and CHD patients. STUDY DESIGN: Descriptive (cross-sectional) study with prospective mortality follow-up. METHODS: We examined 1729 chronic patients with AVD (mean age 65.9 (±SD 9.6) years), 964 with CHD, and 765 poststroke (pooled data of Czech samples of EUROASPIRE III, IV, and the ESH stroke survey). The interview was performed 6-36 months after the coronary event/revascularization or the first ischemic stroke, while the mortality follow-up 5 years after this interview. RESULTS: Poststroke patients had a significantly higher risk of persistent smoking, blood pressure ≥140/90 mmHg and LDL ≥2.5 mmol/L than CHD patients [odds ratios adjusted for age, gender and survey were 1.63 (95% CI: 1.13-2.33), 1.38 (95% CI: 1.13-1.69) and 2.26 (95% CI: 1.84-2.78), respectively]. In contrast, poststroke patients showed a lower risk of inappropriate glucose control and hypertriglyceridemia [0.66 (95%CI: 0.54-0.82) and 0.74 (95%CI: 0.61-0.91), respectively]. The prescription rates of antiplatelets/anticoagulants, antihypertensives and statins were also significantly lower in poststroke than in CHD patients (89.4 vs 93.7, 85.9 vs 97.5, and 57.7 vs 89.8, respectively). Mortality analysis was performed in a subsample of 815 subjects interviewed in 2006/07. The 5-year all-cause mortality rates were 25.8% and 13.3% in poststroke and coronary patients, respectively (P = 0.0023); the hazard ratio for stroke adjusted for major risk factors was 1.85 (95% CI: 1.31-2.63). CONCLUSIONS: Compared to CHD patients, poststroke patients are strongly handicapped in terms of poor adherence to secondary prevention target, prescription of basic pharmacotherapies and mortality risk.

Tobacco smoking strongly modifies the association of prothrombin G20210A with undetermined stroke: consecutive survivors and population-based controls.

OBJECTIVE: Due to contradictory results of previous studies evaluating the association between ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS patients, particularly those older than 60 years, is not recommended. We evaluated the differences in the distribution of rs6025 and rs1799963 polymorphisms according to IS subtypes and their interaction with smoking. METHODS: We conducted a case-control study of 423 hospital-based consecutive survivors of their first-ever IS and 614 population-based controls. Survivors (18-81 years) with IS documented by brain imagining were examined at a median of 16 months after the index event. The stroke subtype was categorized using the Causative Classification of Stroke System. Controls (50-75 years) were free of a history of stroke/TIA, coronary heart disease, and venous thromboembolism. RESULTS: Age- and gender-adjusted prevalence of individuals carrying at least one copy of the rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion, and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR: 3.67; 95% CI: 1.52-8.85; p = 0.004). There was strong evidence of rs1799963 × smoking synergistic interaction (OR: 5.14; 95% CI: 1.65-16.01; p = 0.005). There was no association of rs6025 with IS in general, or with any subtype. CONCLUSIONS: In our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers.

Fibroma cemento osificante: análisis clínico, radiológico e histológico de 2 casos en una misma familia / Cemento-ossifying fibroma: clinical, radiological and histological analysis of 2 cases in one family

El Fibroma Cemento Osificante (FCO) es una lesión pseudo tumoral benigna de origen odontogénico, que se ubica preferentemente a nivel de molares y premolares mandibulares. Nuestro objetivo es presentar casos de FCO dentro de una misma familia, describiendo las características clínicas, radiográficas, histológicas, tratamiento y seguimiento de cada uno de ellos. Dos pacientes hermanos con FCO mandibulares atendidos en el Hospital de Carabineros fueron incluidos en este estudio. La evolución completa de cada caso es expuesta, resaltando el componente familiar de esta patología poco prevalente. Todos los pacientes fueron tratados con remoción completa de la lesión y relleno del defecto óseo con injerto autólogo de cresta iliaca o con injerto óseo particulado sintético (ChronOS®). Un paciente presento recidiva de la lesión y posteriormente un nuevo FCO en el lado contra lateral. En este tipo de lesiones, es muy importante valerse de todas las herramientas diagnosticas que estén a nuestro alcance, ya que la baja ocurrencia de estas lesiones, junto con la gran similitud tanto clínica, radiográfica e histológica que presenta con otras entidades patológicas de los maxilares, hacen que un estudio superficial, puedan llevar a un diagnostico y tratamiento erróneo, afectando la calidad de vida del paciente. El tratamiento de estas lesiones es conservador, y las recidivas son raras.

The Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of odontogenic origin, that is preferentially localized in the molar and premolar mandibular area. Our goal is to present cases of COF that occurred within the same family, describing clinical, radiological and histological characteristics, in addition to treatment and monitoring of each case. Two patients who are brothers, treated at the Hospital de Carabineros, who had mandibular COF, were included in this study. The complete evolution of each case is presented, highlighting the family component of this uncommon disease. All patients were treated with complete removal of the lesion and filling the bone defect with autologous iliac crest graft or synthetic particulated bone graft (ChronOS®). One patient had recurrence of the injury and then presented a new COF on the contralateral side. In this type of injury it is very important to use all the diagnostic tools within our reach. The rarity of these lesions, and the great similarity of both clinical, radiological and histological features with other pathological conditions of the jaws, and a poorly conducted study can lead to wrong diagnosis and treatment affecting the quality of life of patients. The treatment of these lesions is conservative, and relapses are rare.

Tratamiento de fracturas en mandíbulas atróficas: presentación de dos casos clínicos / Management of Atrophic Mandible Fractures: Report of Two Clinical Cases

El siguiente trabajo tiene por objetivo presentar la experiencia del equipo de Cirugía Maxilofacial del Hospital San José, para el manejo de las fracturas en mandíbulas atróficas, reportando el tratamiento médico-quirúrgico y evolución post operatoria de casos clínicos. Se presentan dos casos clínicos de pacientes de sexo femenino, con enfermedades sistémicas de base, edéntulas, con diagnóstico de fractura en mandíbula atrófica consecutivos a caídas de nivel. De los casos tratados, el equipo logró resultados satisfactorios, mediante un tratamiento integral para los pacientes con este tipo de fracturas, basado en protocolos actuales encontrados en la literatura. El tratamiento de elección para este tipo de fracturas corresponde a la reducción anatómica quirúrgica y fijación mediante placas y tornilos de osteosíntesis. Fundamentado por sus favorables resultados y a la rápida rehabilitación funcional del paciente. El manejo multidisciplinario es fundamental para tratar este tipo de pacientes, por la posible concomitancia de enfermedades de base que pudiesen poseer estos pacientes.

The objective of the present case report is to present the experience of the maxillofacial surgery team of the Hospital San Jose in the management of atrophic mandible fracture, through the medical-surgical treatment and post-operatory evolution of two clinical cases. We studied two women with systemic conditions, edentulous with a diagnosis of atrophic mandible fracture subsequent to fall injury. In all treated cases the surgical team achieved satisfactory results through an integral treatment of patients with this type of fracture, based on actual literature reported protocols. The treatment of choice for this type of fractures is an anatomical open reduction, by internal fixation with osteosynthesis plates and screws on the basis of favorable results and functional rehabilitation of patients. The multidisciplinary management is fundamental for treatment of this type of patient due to the concomitant systemic conditions of these patients.

The interaction of endothelial nitric oxide synthase polymorphism and current smoking in terms of increased arterial stiffness.

Nitric oxide belongs to the most important factors influencing structural and functional properties of vessel wall. Both genetic and environmental factors may influence its metabolism. The aim of this study was to explore whether two common polymorphisms of endothelial nitric synthase (eNOS) may, jointly with smoking, influence the stiffness of large arteries, quantified as pulse wave velocity (PWV). One hundred ninety four subjects free of manifest atherosclerotic disease or chronic pharmacotherapy were selected from population-based postMONICA study. PWV´s were measured using Sphygmocor® device between carotic and femoral arteries (aortic PWV) and between femoral and tibialis-posterior arteries (peripheral PWV). Two common polymorphisms, T786C and G894T, were assessed. Among current smokers, homo- or heterozygous carriers of T786C mutation showed significantly higher peripheral PWV than normal genotype carriers (14.0 vs 10.7 m/s, p<0.002); the same was true for the carriers of G894T mutation (13.9 vs 11.0 m/s, p<0.015). No differences were found in non-smokers, and neither of the eNOS polymorphisms influenced aortic PWV in our setting. In conclusion, genetically determined disorder of nitric oxide metabolism was associated with increased stiffness of peripheral, muscular-type arteries in generally healthy, untreated subjects, but only in the interaction with current smoking.

Detection of disseminated tumour cells in mediastinoscopic lymph node biopsies and endobronchial ultrasonography-guided transbronchial needle aspiration in patients with suspected lung cancer.

PURPOSE: Ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes (EBUS-TBNA) is apparently more accurate for cancer diagnosis than standard transbronchial needle aspiration (TBNA), but it is less sensitive than mediastinoscopy. The detection of disseminated tumour cells in transbronchial needle aspiration and mediastinoscopic biopsies could improve staging and might be helpful concerning indications for neoadjuvant regimen. The goal of this study was to develop a quantitative method for the detection of disseminated tumour cells (DTCs) in lymph node samples from patients with suspected lung cancer. PATIENTS AND METHODS: We compared in a prospective trail EBUS-TBNA (n=58 patients, 86 samples) and mediastinoscopy (n=22 patients, 37 samples) in two largely independent cohorts of lung cancer patients. Eleven patients, 14 samples were analysed using both methods. Patients without evidence of malignant disease were available as controls for EBUS-TBNA (n=20 patients, 28 samples) and mediastinoscopy (n=6 patients, 8 samples). Real-time quantitative mRNA analysis was performed for the cytokeratin 19 (CK19) and MAGE-A genes (MAGE-A 1-6, MAGE-A12) as markers, using a LightCycler 480 instrument. RESULTS: CK19 mRNA expression in EBUS-TBNA samples was detected in 84/86 (98%) and in 28/28 control samples (100%). After mediastinoscopy 16/37 (43%) samples of lung cancer patients were CK19 mRNA positive while controls showed no CK19 mRNA expression (0/8). MAGE-A expression was detectable in 42/86 (49%) EBUS-TBNA samples and in 13/37 (35%) mediastinoscopy samples. MAGE-A expression was detected in EBUS-TBNA controls in 3/28 (11%) and 1/8 (12%) mediastinoscopy controls. High MAGE-A expression correlated with increased tumour stage. CONCLUSION: Since CK19 expression was detected in all EBUS-TBNA samples from the control patients, but not in mediastinoscopy samples, we conclude that CK19 is not suitable as a marker for disseminated tumour cells in samples attained by EBUS-TBNA. One possible explanation is a contamination with epithelial cells from the bronchial tubes. MAGE-A genes are promising markers for disseminated tumour cells in lymph nodes in patients with suspected lung cancer which merit further investigation.

Asymmetric dimethylarginine and the effect of folate substitution in children with familial hypercholesterolemia and diabetes mellitus type 1.

A recently discussed cardiovascular risk factor, asymmetric dimethylarginine (ADMA), is known to act as an endogenous inhibitor of endothelial nitric oxide synthase. The aim of this study was to establish 1) the relationship between ADMA and ultrasonographically or biochemically determined endothelial dysfunction in children, and 2) the effect of folate supplementation on these parameters. The study cohort included 32 children with familial hypercholesterolemia (FH), 30 with diabetes mellitus type 1 (DM1) and 30 age-matched healthy children as the control group. Furthermore, twenty-eight randomly selected FH and DM1 children were re-examined after 3-months supplementation with folic acid. Baseline levels of ADMA and oxidized low density lipoproteins (oxLDL) were significantly higher in FH group than in DM1 and healthy children. Children in DM1 group had significantly lower concentration of homocysteine, but ADMA levels were normal. Folic acid supplementation significantly lowered homocysteine and hsCRP levels in both FH and DM1 group; however, ADMA and oxLDL concentrations remained unaltered. In conclusion, ADMA and oxLDL appear to be associated with endothelial dysfunction in children with FH. Administration of folic acid did not influence these markers in both FH and DM1 children.

Mild hyperhomocysteinaemia is associated with increased aortic stiffness in general population.

Total homocysteine (tHcy) level was identified as a strong and independent predictor of cardiovascular events. We investigated the association between tHcy and mechanical properties of large arteries in a random, general population-based sample of 251 subjects (mean age 48 years). Large artery properties, such as aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation index of radial artery were measured using semi-automatic Sphygmocor device. Aortic PWV (APWV) positively correlated with tHcy (r = 0.28, P<0.0001), and a significant increasing trend of APWV was found by tHcy quartiles (P = 0.0003 by ANOVA). This association remained significant after adjustment for conventional cardiovascular risk factors (age, gender, smoking, overweight, hypertension, dyslipidaemia and impaired glucose metabolism) and for usual homocysteine confounders (folate, B12, renal function). Subjects with mild hyperhomocysteinaemia (i.e. with tHcy > or = 15 micromol/l) had 2.74 times higher risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such association was found either for PWV measured at lower extremity or for radial augmentation index. In conclusion, in our series of subjects from general population, we found a strong and independent relationship between homocysteine concentration and APWV, a parameter of stiffness of central arteries.

[Recommendations for the treatment of tobacco dependence]. / Doporucení pro lécbu závislosti na tabáku.

This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.

Educational level and risk profile of cardiac patients in the EUROASPIRE II substudy.

STUDY OBJECTIVE: To ascertain, whether, conventional risk factors and readiness of coronary patients to modify their behaviour and to comply with recommended medication were associated with education in patients with established coronary heart disease. DESIGN AND METHODS: EUROASPIRE II was a cross sectional survey undertaken in 1999-2000 in 15 European countries to ascertain how effectively recommendations on coronary preventions are being followed in clinical practice. Consecutive patients, men and women

[D-dimers in the diagnosis of deep venous thrombosis]. / D-dimery v diagnostice hluboké zilní trombózy.

D-dimers (D-d) are degeneration products of fibrin. According to some recommendations (Lee et al., Ann Rev Med, 2002; 53: 15-33) the vein thromboembolism may be excluded by the determination of D-dimers level especially when the probability of diagnosis of deep vein thrombosis is less strong. The determination of D-dimers with made possible was the development of monoclonal antibodies and their detection is based on the determination using the principle of ELISA or agglutination techniques. An increased D-d level is not completely specific for venous thrombo-embolism; it may be enhanced during tumorous diseases, infections, kidney failure etc. In contrast, a negative result of the test is highly sensitive for exclusion of deep vein thrombosis or pulmonary embolism (sensitivity 90% to 100%). The authors also present their own results of a prospective study on the dynamism of D-dimer level in plasma of patients with deep vein thrombosis demonstrated by sonography at the time of start and in the course of the anticoagulant therapy. D-dimers were determined by two methods, the quantitative agglutination latex method and the rapid VIDAS ELISA method. At the time of admission, an increased level was established in up to 80% of patients using the VIDAS method and in 70% using the latex method. In the period of five to seven days after the beginning of treatment the proportions were 75% and 60%, respectively, according to the method used. After six weeks, a slightly elevated level above normal may be expected in 1/3 of patients and less than in 1/5 of patients in the later months.

[Changes in the risk profile and the development of hypertension in the population of Plzen 1987-1989 and 1995-1996]. / Zmeny rizikového profilu a vývoj hypertenze v plzenské populaci mezi lety 1987-1989 a 1995-1996.

OBJECTIVE: To evaluate risk factors and the general risk profile in a longitudinally followed-up cohort of the Plzen population. MATERIAL AND METHODS: The investigation was made in a cohort of 332 men and 280 women selected from the epidemiological study PILS II (Plzen longitudinal study) examined in 1987-1989 and 1995-1995. Both investigations adhered to the standard protocol. Anamnestic data were assessed, anthropometric parameters (BMI). Blood pressure (BP) was assessed by means of a mercury sphygmomanometer using the standard procedure, biochemical parameters were examined from a blood sample on fasting in the routine laboratories of the Faculty Hospital Plzen. Changes of individual factors were evaluated by the paired Wilcoxon test and chi 2 group test resp. The global coronary risk was calculated by means of logistic coefficients from the Framingham study. RESULTS: In the cohort which aged on average by 7.6 years the number of smokers decreased in men by 8.1% and by 3.6% in women. The blood pressure increased significantly in both sexes, there was an increase in the number of hypertensive subjects by 26.8% in men and 21.7% in women. In men there was a significant decrease of non-HDL cholesterol, in women, there was a significant increase of subjects with diabetic dyslipidaemia. The total coronary risk (Framingham score) increased after standard transposition to the age of 60 years only by 0.5% in men and women, which reflects the risk due to increased BP. The standard of treatment of hypertension was quite unsatisfactory. When using criteria SBP > or = 140 and/or DBP > or = 90 mm Hg during the second examination 71% of the patients remained without treatment. The number of subjects not aware of hypertension declined from 54% to 19.3% of subjects. A favourable indicator was the finding that there was a decline of hypertensive subjects with a high coronary risk (> or = 20% from ca 11 to 6%). CONCLUSION: During the investigation period in the cohort which to a certain extent represents the Plzen population a certain improvement of the risk profile occurred in particular as regards smoking and disorders of the lipid spectrum, however not as regards the prevalence and treatment of hypertension. Despite the favourable development in the Czech population in the investigated cohort, obviously at the expense of poor control of hypertension, the average coronary risk did not improve.

[Effect of folates, vitamin B12 and life style factors on mild hyperhomocysteinemia in a population sample]. / Vztah folátu, vitaminu B12 a nekterých faktoru zivotního stylu k mírné hyperhomocysteinémii v populacním vzorku.

BACKGROUND: Mild hyperhomocysteinaemia (MHHcy) is a significant and independent risk factor for vascular diseases, however, its causality has not yet been unequivocally confirmed. The total homocysteine (Hcy) blood level is considered a product of genetic and lifestyle interactions, mainly folates, vitamin B12 and pyridoxine intake. In this paper we estimated the influence of these factors on MHHcy in the population. METHODS AND RESULTS: The population sample included 292 males a 251 women, mean age 53.4 years, selected from the population study PILS II. All subjects were examined by a standard protocol for clinical, anthropometrical and laboratory examination. Hcy levels were examined by ion exchange chromatography, all other factors by commercial kits. Statistical analysis was done in quartiles of distribution by Kruskal-Wallis ANOVA, Wilcoxon's un-paired test and multiple logistic regression (stepwise). Serum total Hcy levels were in significant positive associations with age in both sexes, with BMI in males only. Negative associations of Hcy were found with plasma folates and B12 concentrations in both sexes, with alcohol consumption again only in males. Smoking and physical activity and serum methionine concentration were not associated with Hcy levels. The established associations remained significant when adjusted by multiple logistic regression. About 40% of subjects with MHHcy had low folates and/or B12 levels and a deficiency in both vitamins was found in 17% of subjects. In contrast, MHHcy also was assessed in 14% of subjects with high folates and in 17% with high B12 concentration and in as few as in 3.7% of subjects with high concentrations of both vitamins as well. CONCLUSIONS: Nutritional factors, i.e. folates and B12 intake, seem to be the most important ones responsible for Hcy levels. A predominating influence of genetic factors may be assumed in less than one fifth of subjects with MHHcy.

Pharmacokinetics of orally administered estradiol valerate. Results of a single-dose cross-over bioequivalence study in postmenopausal women.

A randomized, single-dose cross-over study in 32 postmenopausal women was performed to demonstrate bioequivalence of two estradiol valerate containing formulations (first sequence of Klimonorm as test preparation). The serum levels of estradiol, free and conjugated estrone were measured until 48 h after an oral dosage of 4 mg estradiol valerate (CAS 979-32-8). The mean AUC(0-48) of estradiol was calculated as 1006.6 +/- 479.4 h x pg x ml-1 (Test) and 1015.2 +/- 555.2 h x pg x ml-1 (Reference). The corresponding (AUC(0-48) of the active metabolite, free estrone, exceeded that of estradiol at 3578.3 h x pg x ml-1 (Test) and 3485.1 h x pg x ml-1 (Reference). Much higher was the AUC(0-48) for conjugated estrone at 132.4 h x ng x ml-1 (Test) and 133.6 h x ng x ml-1 (Reference). Mean estradiol Cmax values of 39.8 +/- 17.7 pg/ml (Test) and 42.9 +/- 21.0 pg/ml (Reference) were attained 8.2 +/- 4.5 h (Test) and 10.0 +/- 5.9 h (Reference) after the administration of 4 mg estradiol valerate. Maximal free estrone concentrations of 163 pg/ml (Test) and 174.3 pg/ml (Reference) were reached after 7.2 h (Test) and 7.5 h (Reference). Maximal conjugated estrone concentrations of 15.5 ng/ml (Test) and 16.2 ng/ml (Reference) were reached after 2.4 h (Test) and 2.0 h (Reference). The terminal elimination half-life of estradiol was calculated at 16.9 +/- 6.0 h (Test) and 15.0 +/- 4.8 h (Reference), that of free estrone at 16.3 h (Test) and 13.5 h (Reference), that of conjugated estrone at 11.8 h (Test) and 10.6 h (Reference). After logarithmic transformation, the 90% confidence intervals of the AUC(0-48) and Cmax ratios for estradiol and also for the metabolites (free and conjugated estrone) were within the acceptance ranges for bioequivalence. Therefore the test preparation and the reference preparation are bioequivalent.

[Analysis of mortality trends in the West Bohemian Region in comparison with the entire Czech Republic 1988-1995]. / Analýza trendu mortality v západoceském regionu v letech 1988-1995 ve srovnání s celou Ceskou republikou.

BACKGROUND: Unfavourable trends in Czech republic (CR) started in the sixties and peaked in the late eighties i.e. in years when a dramatic mortality fall was observed in most western european countries. So, CR belonged among those Eastern European countries in that total and cardiovascular mortality showed increasing and alarming trends. West Bohemia Region (WB) was characterised by the concentration of heavy industry and high environmental pollution. Because of its geographical position on the western frontier, it was generally restricted in capital investment in the past. We wondered whether these phenomenon were reflected in higher mortality rates than in the rest of CR and which changes occurred after the year 1989. METHODS AND RESULTS: We compared the age standardized mortality data from 1988, 91, 93 and 95 in CR and WB for total mortality, cardiovascular mortality, coronary heart disease, strokes, malignancies and respiratory diseases. Data were age-adjusted for "World Population Standards" and rates were given for 100,000 inhabitants. In the whole CR a significant decrease of total, cardiovascular and cancer mortality was observed from 1988 to 1995. In WB these trends were similar, however in comparison to the whole CR the mortality rates remained in each respective period higher for total, cancer (mainly lung cancer) mortality and for non specific respiratory disease. In contrast, the coronary mortality rates in CR and WB were similar, however in WB after a temporary decrease in 1993 a significant increase in 1995 was observed. On the other hand the stroke mortality rates which were until 1993 in WB higher, significantly decreased in 1995 below the rates for CR. The cause of higher mortality rates in WB are far from being clear. To elucidate this observation epidemiologic studies of environmental pollution, life style of the population and socioeconomic factors are necessary, even as a further monitoring of regional mortality rates and trends.