Consensus on hemophilia in Mexico.

Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles, and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion-transmitted infections), or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology characterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

La hemofilia es un trastorno hemorrágico con patrón de herencia ligado al sexo, caracterizado por una incapacidad en la amplificación de la coagulación ocasionada por la deficiencia del factor VIII (hemofilia A o clásica) o del factor IX (hemofilia B). La secuenciación de los genes involucrados en la hemofilia ha permitido la descripción y registro de las principales mutaciones, así como la correlación con los diversos grados de severidad. Las manifestaciones hemorrágicas se relacionan con los niveles de factor deficiente circulante, afectando principalmente al sistema musculoesquelético y en particular a las grandes articulaciones (rodillas, tobillos y codos). El presente documento hace una revisión y consenso de los principales aspectos genéticos de la hemofilia, desde el patrón de herencia y el concepto de mujeres portadoras, la fisiopatología y clasificación de la enfermedad, los estudios básicos y de confirmación ante la sospecha de hemofilia, y de los diversos esquemas de tratamiento basados en la infusión del factor de coagulación deficiente hasta las terapias innovadoras libres de factor, así como de las recomendaciones para el manejo de las complicaciones asociadas al tratamiento (desarrollo de inhibidores y/o infecciones transmitidas por transfusión) o secundarias a los eventos hemorrágicos a nivel articular (artropatía hemofílica). La parte final del documento revisa los aspectos clínicos y de tratamiento relevantes de una patología hemorragica caracterizada por la deficiencia adquirida del FVIII mediada por anticuerpos neutralizantes denominada hemofilia adquirida.

Consenso de hemofilia en México / Mexican Consensus in Haemophilia

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Abstract Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion transmitted infections) or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology charachterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

Procollagen type III amino terminal peptide and myocardial fibrosis: A study in hypertensive patients with and without left ventricular hypertrophy.

INTRODUCTION AND OBJECTIVES: An exaggerated accumulation of type I and type III fibrillar collagens occurs throughout the free wall and interventricular septum of patients with primary hypertension and left ventricular hypertrophy (LVH). In the present study the serum concentration of procollagen type III amino terminal peptide (PIIIP) was measured to determine the value of this peptide as a potential marker of ventricular fibrosis in hypertensive patients, particularly those with LVH. METHODS: The study population consisted of patients with never-treated mild to moderate essential hypertension and 30 normotensive control subjects. Clinical, echocardiographic, electrocardiographic and biochemical parameters were assessed in all patients. RESULTS: Heart rate, body mass index and levels of blood pressure were increased in hypertensives, particularly those with LVH, compared to normotensive controls. Posterior wall thickness, left ventricular (LV) mass and LV mass index, and serum PIIIP concentration were also increased in hypertensives, with significant differences between the two hypertensive groups. The ratio between maximal early and late transmitral flow velocity measured during diastole was lower in hypertensives, particularly those with LVH, than in normotensive controls. CONCLUSIONS: The increase in PIIIP indicates that type III collagen synthesis increases in hypertensives, particularly those with LVH, implying that alterations in the heart in hypertension are the result not solely of hypertrophied LV muscle, but also of increased collagen deposition within the ventricular wall and around the coronary vessels. Thus, measurement of serum PIIIP could be a practical and useful tool in the non-invasive assessment of myocardial remodeling in hypertension.

In situ effect of titanium tetrafluoride and sodium fluoride on artificially decayed human enamel.

This study compared in situ the application of 4% titanium tetrafluoride (TiF4) solution and 2% sodium fluoride (NaF) gel on artificial white-spot lesions in human enamel. A crossover, double-blind study using in situ caries models was carried out. Eleven volunteers used an intraoral appliance containing five demineralized human enamel blocks. The blocks (n=170) were randomly divided according to treatment into the following groups: TiF4 (n=55), NaF (n=55), positive control (n=55). A negative control group was composed of demineralized specimens (n=5). The microhardness test was performed using a Knoop penetrator. Energy dispersive spectrometer (EDS) was used to analyze the concentration of titanium, calcium, phosphate and oxygen. The enamel microhardness at different depths for TiF4, NaF and positive control samples was not statistically different (p>0.05). The samples from these three groups had statistically higher microhardness values than the negative control samples (p<0.05). EDS analysis did not provide conclusive results about the penetration of titanium in the TiF4 samples. While in some fragments it had substantial penetration, in other fragments it only had superficial penetration. It was possible to conclude that, under in situ conditions, 4% TiF4 solution and 2% NaF gel were able to remineralize artificial white-spot lesions in human enamel. However, the magnitude of the remineralization did not differ between groups.

In Situ Effect of Titanium Tetrafluoride and Sodium Fluoride on Artificially Decayed Human Enamel

This study compared in situ the application of 4% titanium tetrafluoride (TiF4) solution and 2% sodium fluoride (NaF) gel on artificial white-spot lesions in human enamel. A crossover, double-blind study using in situ caries models was carried out. Eleven volunteers used an intraoral appliance containing five demineralized human enamel blocks. The blocks (n=170) were randomly divided according to treatment into the following groups: TiF4 (n=55), NaF (n=55), positive control (n=55). A negative control group was composed of demineralized specimens (n=5). The microhardness test was performed using a Knoop penetrator. Energy dispersive spectrometer (EDS) was used to analyze the concentration of titanium, calcium, phosphate and oxygen. The enamel microhardness at different depths for TiF4, NaF and positive control samples was not statistically different (p>0.05). The samples from these three groups had statistically higher microhardness values than the negative control samples (p<0.05). EDS analysis did not provide conclusive results about the penetration of titanium in the TiF4 samples. While in some fragments it had substantial penetration, in other fragments it only had superficial penetration. It was possible to conclude that, under in situ conditions, 4% TiF4 solution and 2% NaF gel were able to remineralize artificial white-spot lesions in human enamel. However, the magnitude of the remineralization did not differ between groups.

Este estudo comparou in situ a aplicação de uma solução de tetrafluoreto de titânio (TiF4) a 4% e um gel de fluoreto de sódio (NaF) sobre lesões de mancha branca artificiais em esmalte dentário humano. Foi realizado um estudo cruzado, duplo-cego utilizando um modelo in situ de cárie. Onze voluntários usaram um aparelho intraoral contendo cinco blocos de esmalte humanos desmineralizados. Os blocos (n = 170) foram divididos aleatoriamente de acordo com o tratamento nos seguintes grupos: TiF4 (n = 55) , NaF (n = 55) , controle positivo (n = 55). Um grupo controle negativo foi composto de espécimes desmineralizados (n = 5). O teste de microdureza foi realizado utilizando um penetrador Knoop. Espectrômetro de energia dispersiva (EDS) foi utilizado para analisar a concentração de titânio, cálcio, fosfato e oxigênio. A microdureza do esmalte em diferentes profundidades para as amostras dos grupos TiF4, NaF e controle positivo não diferiram estatisticamente (p>0,05). As amostras destes três grupos apresentaram valores de microdureza estatisticamente maiores do que as amostras do controle negativo (p<0,05). A análise EDS não forneceu resultados conclusivos sobre a penetração de titânio nas amostras de TiF4. Apesar de apresentar, em alguns fragmentos, uma penetração substancial, em outros fragmentos apresentou apenas penetração superficial. Foi possível concluir que, sob as condições do estudo in situ, a solução de TiF4 a 4% e o gel de NaF a 2% foram capazes de remineralizar lesões de mancha branca em esmalte humano. No entanto, a magnitude da remineralização não diferiu entre os grupos.

[Hypertension and exercise]. / Hipertensão arterial e exercício físico.

Levels of physical activity in modern urbanized society are clearly insufficient to maintain good health, and to prevent cardiovascular and other disease. Aerobic exercise is almost completely free of secondary effects, and is a useful adjunctive therapy in treating hypertension. There are several possible mechanisms to account for the beneficial effects of exercise in reducing blood pressure, the resulting physiological effects usually being classified as acute, post-exercise or chronic. Variations in genetic background, hypertension etiology, pharmacodynamics and pharmacokinetics may explain the different blood pressure responses to exercise among hypertensive patients. The present review discusses the different pathophysiological aspects of the response to exercise in hypertensives, including its modulators and diagnostic and prognostic usefulness, as well as the latest guidelines on prescribing and monitoring exercise regimes and drug therapy in the clinical follow-up of active hypertensive patients.

The importance of dental care for a child with severe congenital neutropenia: a case report.

Congenital neutropenia is characterized by a decrease in the absolute number of circulating neutrophils and an increased susceptibility to infections. This paper describes the case history of a child with severe congenital neutropenia who had aggressive periodontitis associated with generalized carious lesions. She had Kostmann syndrome, which is associated with recessive mutation of the HAX-1 gene. She had extensive dental caries, which is not common in patients with Kostmann syndrome. The caries caused oral pain and loss of weight and could have been avoided if the parents had received early oral hygiene instructions, and if the child had received regular, professional dental care.

Prevalence, awareness, treatment and control of hypertension in Portugal. The PAP study.

The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the level of awareness, treatment, and control of hypertension in the Portuguese adult population. The study was conducted in 2003, using a multistage cluster sampling method to select a representative national sample. A total of 5023 adults, aged 18 to 90 years, were examined. Three blood pressure measurements were obtained by trained observers using an OMRON M4-1 sphygmomanometer after a 5-minute seated rest. Information on history of hypertension and use of antihypertensive medication was obtained using a standard questionnaire. Hypertension was defined as mean systolic blood pressure > or =140 mmHg and/or diastolic blood pressure > or =90 mmHg, or use of antihypertensive medication. Overall, 42.1% of the Portuguese adult population aged 18 to 90 years, representing 3,311,830 people, would have hypertension. The age-specific prevalence of hypertension in the three age-groups studied--under 35 years, 35-64 years, and over 64 years--was 26.2%, 54.7% and 79% in men and 12.4%, 41.1% and 78.7% in women respectively. Among hypertensive subjects, only 46.1% were aware of their high blood pressure, 39.0% were taking antihypertensive medication, and 11.2% had their blood pressure controlled (<140/90 mmHg). Our results indicate that hypertension is highly prevalent in Portugal. The percentages of hypertensives who are aware of their condition, are being treated, and whose hypertension is controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of hypertension in Portugal.

Thyroid morphology and function in adults with untreated isolated growth hormone deficiency.

OBJECTIVE: GH influences thyroid function and anatomy. Although goiter is frequent in acromegalic patients, the effects of GH deficiency (GHD) are difficult to assess, because hypopituitaric subjects who lack GH often also have a partial or complete deficit of TSH. STUDY DESIGN: We studied thyroid morphology and serum levels of thyroid hormones in adult members of a large Brazilian kindred with untreated isolated GHD due to a homozygous mutation in the GHRH receptor gene (GHRHR; nine men and 15 women; GHD group) and compared them to subjects heterozygous for the same mutation (eight men and 10 women; HET group) and subjects homozygous for the wild-type allele [seven men and 11 women; control (CO) group]. RESULTS: GHD subjects had a smaller thyroid volume (TV) than HET and CO. The TV of the HET group was intermediate between those of the GHD and CO groups. When TV was corrected by body surface area, it remained smaller in the GHD and HET groups than in the CO group, but the difference between GHD and HET groups disappeared. The GHD group had lower serum T3 levels than the CO group and higher free T4 levels than HET and CO groups. CONCLUSIONS: Individuals with severe untreated GHD due to a homozygous GHRHR mutation and heterozygous carriers of the same mutation have smaller TV than normal subjects, suggesting that GH has a permissive role in the growth of the thyroid gland. In addition, GHD subjects have reduced serum total T3 and increased serum free T4, suggesting a reduction in the function of the deiodinase system.

Lack of adequate blood pressure control in the morning and evening periods in medicated hypertensive patients considered to be controlled in the office.

BACKGROUND AND AIM: In hypertensive patients tight blood pressure (BP) control during the critical morning and evening periods may be relevant for preventing cardiovascular events, which most frequently occur at these times of the day. METHODS: In a prospective study we evaluated 24h ambulatory BP (ABP) values (24h, daytime, nighttime, morning period between 6-10 am and evening period between 6-10 pm), in 103 hypertensive patients (HTs), aged between 18-79 years, considered to be controlled in the office in the previous two months (office BP < 140/90 mmHg, 2 x 3 readings, before taking medication), who were being treated with antihypertensive drugs taken once daily in the morning. Based on ABP data, HTs were considered to have good BP control if daytime BP values were < 135/85 mmHg, < 133.1/85.4 mmHg during the morning period, and < 138.1/89.3 mmHg during the evening period. Otherwise control of ABP was considered poor. These limits correspond to the upper 95% confidence limits of BP calculated for each period in a normotensive control population of 210 subjects age-matched to the HTs. RESULTS: Of the 103 HTs, 39 were under monotherapy and the remaining 64 on combination regimens (34 with two drugs, 29 with three and one with four). Based on ABP data of the 103 HTs, poor ABP control was observed in 36 (35%) in the morning period, in 24 (23%) in the evening period and in 29 (28%) for daytime BP values. ABP values during both the morning and evening periods correlated significantly with daytime values (r = 0.72 and r = 0.89 respectively, p < 0.01) but not with office values. CONCLUSIONS: A significant proportion of treated HTs who are considered to be controlled in the office present abnormally high ABP levels, particularly in the critical early morning period, but also during the evening and throughout the daytime period.

Prevalence, awareness, treatment and control of hypertension in Portugal: the PAP study.

BACKGROUND: The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment and control in the Portuguese adult population. METHODS: This study was conducted in 2003, and a multistage cluster sampling method was used to select a national representative sample. A total of 5023 adults, age 18-90 years, were examined. Three blood pressure measurements were obtained by trained observers using an OMROM M4-I sphygmomanometer after a 5-min sitting rest. Information on the history of hypertension and the use of antihypertensive medications was obtained by use of a standard questionnaire. RESULTS: Hypertension was defined as a mean systolic blood pressure > or = 140 mmHg and/or diastolic blood pressure > or = 90 mmHg, or the use of antihypertensive medications. Overall, 42.1% of the Portuguese adult population aged 18-90 years, representing 3 311 830 people, had hypertension. The age-specific prevalence of hypertension in the three age groups studied--younger than 35 years, 35-64 years old and older than 64 years--was 26.2, 54.7 and 79% in men and 12.4, 41.1 and 78.7% in women, respectively. Among hypertensive patients, only 46.1% were aware of their high blood pressure, 39.0% were taking antihypertensive medication and 11.2% achieved blood pressure control (< 140/90 mmHg). CONCLUSIONS: Our results indicate that hypertension is highly prevalent in Portugal. The percentages of those with hypertension that are aware, treated and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection and treatment of hypertension in Portugal.

Resistência ao cisalhamento e remanescente adesivo de diferentes sistemas ortodônticos / Shear bond strength and adhesive remnant index of different orthodontic systems

O objetivo deste estudo foi avaliar a resistência ao cisalhamento (RC) e o índice de remanescente adesivo (ARI) de diferentes sistemas de colagem ortodôntica. Um total de 60 corpos-de-provas foram distribuídos (n=15) nos grupos: GI (Concise Ortodôntico), GII (Concise Ortodôntico diluído), GIII (Alpha Plast Ortodôntico) e GIV (Concise Restaurador). Verificou-se, através do teste de Kruskal-Wallis, que não houve diferença estatisticamente significante quanto à RC de GI, GII e GII (p>0,05), sendo todos eles superiores ao GIV (p<0,05). Quanto ao ARI, o comportamento do GIV foi semelhante aos demais grupos (p>0,05), entretanto, o GII foi estatisticamente superior ao GI e GII (p<0,05).

Hormônio do crescimento ou somatotrófico: novas perspectivas na deficiência isolada de GH a partir da descrição da mutação no gene do receptor do GHRH nos indivíduos da cidade de Itabaianinha, Brasil / Growth or somatotrophic hormone: new perspectives in isolated GH deficiency after description of the mutation in the GHRH receptor gene in individuals of Itabaianinha county, Brazil

Além de influenciar o crescimento corpóreo, o hormônio do crescimento, ou somatotrófico, desempenha importante papel no metabolismo, composição corporal, perfil lipídico, estado cardiovascular e longevidade. Seu controle é multi-regulado por hormônios, metabólitos e peptídeos hipotalâmicos. Dados sobre a Deficiência Isolada de GH (DIGH) obtidos a partir da descrição da mutação IVS1+1G®A no gene do receptor do hormônio liberador do GH (GHRH-R) em indivíduos da cidade de Itabaianinha, SE, são revisados. São abordadas novas perspectivas sobre o modelo de resistência ao GHRH, a importância do GHRH no controle da secreção de GH, a freqüência das mutações do gene do GHRH-R, a relevância diagnóstica do IGF-I e os achados metabólicos, cardiovasculares e de qualidade de vida nestes indivíduos.

[Growth or somatotrophic hormone: new perspectives in isolated GH deficiency after description of the mutation in the GHRH receptor gene in individuals of Itabaianinha County, Brazil]. / Hormônio do crescimento ou somatotrófico: novas perspectivas na deficiência isolada de GH a partir da descrição da mutação no gene do receptor do GHRH nos indivíduos da cidade de Itabaianinha, Brasil.

In addition to stimulating body growth, growth or somatotrophic hormone plays an important role in metabolism, body composition, lipid profile, cardiovascular status and longevity. Its control is multiregulated by hormones, metabolites and hypothalamic peptides. Obtained data of the isolated growth hormone deficiency (IGHD) after the description of the IVS1+1G-->A GHRH receptor gene mutation in individuals of Itabaianinha County are reviewed. New perspectives about the growth hormone resistance model, the importance of GHRH in the control of GH secretion, the frequency of GHRH-R gene mutations, the diagnostic relevance of IGF-I and the metabolic, cardiovascular and quality of life findings are approached.