Osteoclastogenesis, inflammatory cytokines and biomarkers of bone metabolism in psoriatic arthritis

RESUMO:A artrite psoriática (AP) é uma doença inflamatória crónica caracterizada por várias manifestações nas articulações, nas enteses e na pele. A formação de novo osso após inflamação nas enteses é um dos aspetos mais intrigantes desta doença. Os mecanismos celulares e moleculares deste processo ainda não são completamente conhecidos. Este estudo tem como objetivo compreender melhor os mecanismos subjacentes à formação e reabsorção óssea, bem como o efeito de anti-inflamatórios não esteroides (AINEs) nestes processos. Para atingir este objetivo foram quantificados biomarcadores do metabolismo ósseo e citocinas inflamatórias em doentes AP, antes e após terapêutica com AINEs. Os biomarcadores selecionados foram marcadores de remodelação óssea como CTX-I e P1NP, fatores de diferenciação e ativação de osteoclastos como o RANKL e a OPG, inibidores da via de sinalização Wnt, nomeadamente o DKK-1 e a SOST e ainda citocinas pro-inflamatórias como a IL-22 e a IL-23 e a prostaglandina PGE2. Neste contexto foram também estabelecidas culturas celulares de monócitos, isoladas de doentes AP e de controlos saudáveis. Os monócitos foram cultivados in vitro em condições não estimuladas e estimuladas e realizados dois ensaios funcionais: coloração com TRAP e ensaio de reabsorção. Foi observada uma diminuição nos níveis séricos de CTX-I e OPG em doentes AP em relação aos controlos. De igual forma os níveis séricos de SOST encontram-se significativamente mais baixos, em comparação com os controlos saudáveis. Estes valores de SOST são semelhantes aos dos doentes com espondilite anquilosante (EA), documentados anteriormente. Os ensaios com osteoclastos confirmaram a necessidade da presença de RANKL para estimulação da osteoclastogénese e que o celecoxib parece ter um papel inibitório neste processo. Os resultados obtidos sugerem que a população de doentes com AP analisados têm baixos níveis de reabsorção óssea e alguma atividade na formação óssea. --------------------------- ABSTRACT: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by several manifestations involving the joints, enthesis and the skin. New bone formation after inflammation at enthesis site has been one of the most intriguing aspects of the disease. Cellular and molecular mechanisms in this process are still not completely understood. This study aims to understand better the mechanisms underlying bone formation and resorption and the effect of non-steroid anti-inflammatory drugs (NSAIDs) in these processes. To access that, biomarkers of bone metabolism and inflammatory cytokines were measured in PsA patients’ serum before and after NSAID therapy. These selected biomarkers were bone turnover markers such as CTX-I and P1NP, osteoclast differentiation and activation factors RANKL and OPG, Wnt pathway inhibitors DKK-1 and SOST and pro-inflammatory cytokines IL-22, IL-23 and prostaglandin PGE2. In this context monocyte cell culture was also established after PBMC isolation from PsA patients and healthy controls. Monocytes were cultured in vitro under unstimulated and stimulated conditions and two functional assays were performed: TRAP staining and resorption pit assay. It was demonstrated that CTX-I and OPG serum levels in PsA patients were lower than controls. SOST levels were extremely decreased in comparison with controls, resembling the ankylosing spondylitis patients results already documented. Osteoclast assays confirmed the need of RANKL in stimulating osteoclastogenesis and that celecoxib seems to have an inhibitor role in this process. The results obtained suggest that PsA patient population analyzed in this study have low bone resorption levels and some bone formation activity.

Primary cilia and the regulation of hedgehog signaling: link to cardiac development

RESUMO: As células eucarióticas evoluíram um sistema de sinalização complexo que lhes permite responder aos sinais extracelulares e intracelulares. Desta forma, as vias de sinalização são essenciais para a sobrevivência da célula e do organismo, uma vez que regulam processos fundamentais, tais como o desenvolvimento, o crescimento, a imunidade, e a homeostase dos tecidos. A via de transdução de sinal Hedgehog (Hh) envolve o receptor Patched1 (Ptch1), que tem um efeito inibidor sobre a proteína Smoothened (Smo) na ausência dos seus ligandos, as proteínas Sonic hedgehog (Shh). Estas proteínas são reguladores fundamentais do desenvolvimento embrionário, como ilustrado pelas malformações drásticas observadas em embriões humanos e de murganho com perturbações da transdução de sinal da via Hh e que incluem polidactilia, defeitos craniofaciais e malformações ósseas. Igualmente importantes são as consequências da ativação inapropriada da via de sinalização Hh na formação de tumores. Curiosamente, os componentes desta via localizam-se nos cílios primários. Além disso, demonstrou-se que esta localização é crucial para a sinalização através da via Hh. Na presença dos ligandos, Ptch1 é internalizado e destinado a degradação ou sequestrado num compartimento da célula de onde não pode desempenhar o seu papel inibitório. A proteína Arl13b é uma pequena GTPase pertencente à família Arf/Arl da superfamília Ras de pequenas GTPases e foi implicada no síndrome de Joubert, uma ciliopatia caracterizada por ataxia congénita cerebelar, hipotonia, atrso mental e cardiopatia congénita. Murganhos deficientes para Arl13b, chamado hennin (hnn) morrem morrem prematuramente ao dia 13,5 de gestação (E13,5) e exibem anomalias morfológicas nos cílios que levam à interrupção da sinalização Hh. Além disso, a Arl13b está diretamente envolvida na regulação da via Hh, controlando a localização de vários componentes desta via nos cílios primários. Neste trabalho, mostramos que a Arl13b se localiza em circular dorsal ruffles (CDRs), que são estruturas de actina envolvidas em macropinocitose e internalização de recetores, e que regula a sua formação. Além disso, aprofundámos o conhecimento do processo de ativação da via de sinalização Hh, mostrando que as CDRs sequestram seletivamente e internalizam o recetor Ptch1. As CDRs formam-se minutos após ativação da via por ligandos Shh ou pelo agonista de Smo SAG e continuam a ser formadas a partir daí, sugerindo uma indução contínua da reorganização do citoesqueleto de actina quando a via está ativada. Observámos ainda que a inibição da formação de CDRs através do silenciamento de WAVE1, uma proteína necessária para a formação destas estruturas, resulta na diminuição da ativação da via de sinalização Hh. Além disso, o bloqueio da macropinocitose, que se segue ao fecho das CDRs, através do silenciamento de uma proteína necessária para a cisão de macropinossomas, nomeadamente a proteína BARS, tem um efeito semelhante. Estes resultados sugerem que as CDRs e a macropinocitose são necessárias para a ativação da via de sinalização Hh e indicam que esta via de internalização controla os níveis de sinal Hh. Durante o desenvolvimento, as células proliferativas dependem do cílio primário para a transdução de várias vias de sinalização. A via Hh induz a diferenciação do músculo cardíaco. Por conseguinte, os murganhos deficientes na via de sinalização Hh exibem uma variedade de defeitos de lateralidade, incluindo alteração do looping do coração, como pode ser visto em murganhos deficientes para Arl13b. Por conseguinte, investigámos o papel da Arl13b no desenvolvimento do coração. Mostramos que a Arl13b é altamente expressa no coração de embriões de murganho e de murganhos adultos ao nível do mRNA e da proteína. Além disso, o perfil de distribuição da Arl13b no coração segue o dos cílios primários, que são essenciais para o desenvolvimento cardíaco. Corações de murganhos hnn no estadio E12,5 mostram um canal átrio-ventricular aberto, espessamento da camada compacta ventricular e aumento do índice mitótico no ventrículo esquerdo. Além disso, um atraso de 1 a 2 dias no desenvolvimento é observado em corações de murganhos hnn, quando comparados com controlos selvagens no estadio E13,5. Assim, estes resultados sugerem que a Arl13b é necessária para o desenvolvimento embrionário do coração e que defeitos cardíacos podem contribuir para a letalidade embrionária de murganhos hnn. Em suma, foi estabelecido um novo mecanismo para a regulação dos níveis de superfície do recetor Ptch1, que envolve a remodelação do citoesqueleto de actina e a formação de CDRs após a ativação da via de sinalização Hh. Este mecanismo permite um feedback negativo que evita a repressão excessiva da via através da remoção de Ptch1 da superfície da célula. Além disso, determinou-se que uma mutação de perda de função na Arl13b causa defeitos cardíacos durante o desenvolvimento, possivelmente relacionados com a associação dos defeitos em cílios primários e na sinalização Hh, existentes em murganhos deficientes para Arl13b. A via de sinalização Hh tem tido um papel central entre as vias de sinalização, uma vez que a sua regulação é crucial para o funcionamento apropriada da célula. Assim, a descoberta de um novo mecanismo de tráfego através de macropinocitose e CDRs que controla a ativação e repressão da via de sinalização Hh traz novas perspetivas de como esta via pode ser regulada e pode ainda conduzir à identificação de novos alvos e estratégias terapêuticas. --------------------ABSTRACT: Eukaryotic cells have evolved a complex signaling system that allows them to respond to extracellular and intracellular cues. Signaling pathways are essential for cell and organism survival, since they regulate fundamental processes such as development, growth, immunity, and tissue homeostasis. The Hedgehog (Hh) pathway of signal transduction involves the receptor Patched1 (Ptch1), which has an inhibitory effect on Smoothened (Smo) in the absence of its ligands, the Sonic hedgehog (Shh) proteins. These proteins are fundamental regulators of embryonic development, as illustrated by the dramatic malformations seen in human and mouse embryos with perturbed Hh signal transduction that include polydactyly, craniofacial defects and skeletal malformations. Equally important are the consequences of inappropriate activation of the Hh signaling response in tumor formation. Interestingly, the components of this pathway localize to primary cilia. Moreover, it has been shown that this localization is crucial for Hh signaling. However, in the presence of the ligands, Ptch1 is internalized and destined for degradation or sequestered in a cell compartment where it no longer can play its inhibitory role. ADP-ribosylation factor-like (Arl) 13b, a small GTPase belonging to Arf/Arl family of the Ras superfamily of small GTPases has been implicated in Joubert syndrome, a ciliopathy characterized by congenital cerebellar ataxia, hypotonia, intellectual disability and congenital heart disease. Arl13b-deficient mice, called hennin (hnn) die at embryonic day 13.5 (E13.5) and display morphological abnormalities in primary cilia that lead to the disruption of Hh signaling. Furthermore, Arl13b is directly involved in the regulation of Hh signaling by controlling the localization of several components of this pathway to primary cilia. Here, we show that Arl13b localizes to and regulates the formation of circular dorsal rufles (CDRs), which are actin-basedstructures known to be involved in macropinocytosis and receptor internalization. Additionally, we extended the knowledge of the Hh signaling activation process by showing that CDRs selectively sequester and internalize Ptch1 receptors. CDRs are formed minutes after Hh activation by Shh ligands or the Smo agonist SAG and keep being formed thereafter, suggesting a continuous induction of actin reorganization when the pathway is switched on. Importantly, we observed that disruption of CDRs by silencing WAVE1, a protein required for CDR formation, results in down-regulation of Hh signaling activation. Moreover, the blockade of macropinocytosis, which follows CDR closure, through silencing of a protein necessary for the fission of macropinosomes, namely BARS has a similar effect. These results suggest that CDRs and macropinocytosis are necessary for activation of Hh signaling and indicate that this pathway of internalization controls Hh signal levels. During development, proliferating cells rely on the primary cilium for the transduction of several signaling pathways. Hh induces the differentiation of cardiac muscle. Accordingly, Hh-deficient mice display a variety of laterality defects, including alteration of heart looping, as seen in Arl13b-deficient mice. Therefore, we investigated the role of Arl13b in heart development. We show that Arl13b is highly expressed in the heart of both embryonic and adult mice at mRNA and protein levels. Also, Arl13b localization profile mimics that of primary cilia, which have been shown to be essential to early heart development. E12.5 hnn hearts show an open atrioventricular channel, increased thickening of the ventricular compact layer and increased mitotic index in the left ventricle. Moreover, a delay of 1 to 2 days in development is observed in hnn hearts, when compared to wild-type controls at E13.5. Hence, these results suggest that Arl13b is necessary for embryonic heart development and that cardiac defects might contribute to the embryonic lethality of hnn mice. Altogether, we established a novel mechanism for the regulation of Ptch1 surface levels, involving cytoskeleton remodeling and CDR formation upon Hh signaling activation. This mechanism allows a negative feedback loop that prevents excessive repression of the pathway by removing Ptch1 from the cell surface. Additionally, we determined that the Arl13b loss-offunction mutation causes cardiac defects during development, possibly related to the associated ciliary and Hh signaling defects found in Arl13b-deficient mice. Hh signaling has taken a center stage among the signaling pathways since its regulation is crucial for the appropriate output and function of the cell. Hence, the finding of a novel trafficking mechanism through CDRs and macropinocytosis that controls Hh signaling activation and repression brings new insights to how this pathway can be regulated and can lead to the discovery of novel therapeutic targets and strategies.

Diffuse panbronchiolitis: an underdiagnosed disease? Study of 4 cases in Brazil

BACKGROUND: Diffuse panbronchiolitis is a clinical pathologic condition characterized by chronic inflammation of respiratory bronchioles, with clinical features that position it as a differential diagnosis among the sinopulmonary syndromes. METHODS AND RESULTS: We present 4 cases (1 Black, 2 Japanese descendants, and 1 Japanese), living in Brazil, in which the diagnosis was made by the clinical and radiological features and confirmed by transbronchial biopsy. The clinical findings included chronic sinusitis, productive cough, rhonchi, and wheezes. The pulmonary function tests showed an obstructive pattern. High resolution computerized tomography showed a diffuse nodular pattern, airway ectasia, and airway wall thickening. The biopsy showed interstitial accumulation of foam cells and lymphoid cells in the walls of respiratory bronchioles: 2 of our cases had bronchus-associated lymphoid tissue hyperplasia. We searched for the HLA Bw54 in all of our patients, but only 1 was positive. A low dose macrolide treatment was introduced, resulting in with clinical and functional improvement. A score that rated the extent of nodules, airway ectasia, mucus plugging, and airway wall thickening was applied on pre- and post-treatment High resolution computerized tomography results, revealing an improvement in tomographic pattern related to that observed in the pulmonary function tests. CONCLUSION: We conclude that diffuse panbronchiolitis is a systemic disease that is not exclusive to the Asian population, whose clinical and radiological features should be better known by occidental pulmonary physicians.

Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship?

Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50%) have recurrent wheezing during childhood. Nevertheless, the relationship between these two entities, if any, has not been established. In order to explain this observation, several hypotheses have been proposed. The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. The virus could be a marker of this condition, and the individual predisposition could in turn be related to an individual hypersensitivity to common allergens (atopy), airway hyperreactivity, or to some disorder related to pulmonary anatomy or physiology that was present before the acute episode of bronchiolitis. Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. For this review, we analyzed the studies that discuss these hypotheses with the purpose of clarifying the mechanisms for the important issue of recurrent wheezing in childhood.

Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy

Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. METHOD: Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each) and their respective controls (sham-operated controls - Sh), Sh4 and Sh8 (8 rats each). Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. RESULT: Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg), used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 ± 4.1) than in Sh8 (100.8 ± 1.3), but comparable between aortocaval fistula 4 (50.0 ± 8.9) and Sh4 (84.8 ± 2.3). Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r² = .86, P <.001), whereas left ventricular systolic pressure (r² = 0.73, P = .004) and end-diastolic pressure (r² = 0.55, P = 012) correlated positively and independently with interstitial fibrosis. CONCLUSION: Coronary driving pressure falls and ventricular pressures increase early after aortocaval fistula and are associated with subsequent myocardial fibrosis deposition.

The effect of intravenous zoledronic acid on glucocorticoid-induced multiple vertebral fractures in juvenile systemic lupus erythematosus

Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.

Early loss of splenic Tfh cells in SIV-infected rhesus macaques

Early loss of splenic Tfh cells in SIV-infected rhesus macaques

RNA-seq analysis of the Quercus suber root response to drought

Dissertação de mestrado em Plant Molecular Biology, Biotechnology and Bioentrepreneurship

Reprogramming energy metabolism and inducing angiogenesis : co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas.

Myocardial repair with long-term and low-dose administration of a nitric oxide synthesis inhibitor. Myofibroblasts, type III collagen and fibronectin

OBJECTIVE: To study the healing process of the myocardium in hypertensive rats undergoing inhibition of nitric oxide synthesis. METHODS: Two groups of animals were studied: one received L-NAME, 12mg/kg/day, and the other was a control group. The presence of type III collagen, fibronectin, and alpha-smooth muscle actin-positive cells was assessed by immunohistochemistry. RESULTS: Fibronectin was seen in both early and late lesions, while type III collagen was seen mainly in areas of incomplete healing, situated among myocytes and around the intramyocardial branches of the coronary arteries. Areas representing early and late lesions showed a population of spindle-shaped cells. Immunohistochemistry showed that these cells were positive for alpha-smooth muscle actin. CONCLUSION: In the myocardium of hypertensive rats, the alpha-smooth muscle actin-positive cells are related to the accumulation of type III collagen and fibronectin in the areas of myocardial damage.

Effects of lisinopril on experimental ischemia in rats. Influence of infarct size

OBJECTIVE - Angiotensin-converting enzyme inhibitors (ACEIs) have gained importance in preventing or attenuating the process of ventricular remodeling after myocardial infarction. The significance of infarct size in regard to the response to ACEIs, however, is controversial. This study aimed to analyze the effects of lisinopril on mortality rate, cardiac function, degree of cardiac hypertrophy and fibrosis in rats with different infarct sizes. METHODS - Lisinopril (20 mg/kg/day) dissolved in drinking water was administered to rats immediately after coronary artery occlusion. After being sacrificed, the infarcted animals were divided into two groups: one group of animals with small infarcts (< 40% of the left ventricle) and another group of animals with large infarcts (> 40% of the left ventricle). RESULTS - The mortality rate was 31.7% in treated rats and 47% in the untreated rats. There was no statistical difference between the groups with small and large infarcts in regard to myocardial concentration of hydroxyproline. In small infarcts, the treatment attenuated the heart dysfunction characterized by lower levels of blood pressure and lower values of the first derivative of pressure and of the negative derivative of pressure. The degree of hypertrophy was also attenuated in small infarcts. In regard to large infarcts, no differences between the groups were observed. CONCLUSION - Treatment with the ACEIs had no effect on mortality rate and on the amount of fibrosis. The protective effect of lisinopril on heart function and on the degree of hypertrophy could only be detected in small infarcts

A new surgical approach for treating dilated cardiomyopathy with mitral regurgitation

OBJECTIVE: To evaluate the early outcome of mitral valve prostheses implantation and left ventricular remodeling in 23 patients with end-stage cardiomyopathy and secondary mitral regurgitation (NYHA class III and IV). METHODS: Mitral valvular prosthesis implantation with preservation of papillary muscles and chordae tendinae, and plasty of anteriun cuspid for remodeling of the left ventricle. RESULTS: The surgery was performed in 23 patients, preoperative ejection fraction (echocardiography) varied from 13% to 44% (median: 30%). In 13 patients associated procedures were performed: myocardial revascularization (9), left ventricle plicature repair (3) and aortic prosthese implantation (1). Early deaths (2) occurred on the 4th PO day (cardiogenic shock) and on the 20th PO day (upper gastrointestinal bleeding), and a late death in the second month PO (ventricular arrhythmia). Improvement occurred in NYHA class in 82.6% of the patients (P<0.0001), with a survival rate of 86.9% (mean of 8.9 months of follow-up). CONCLUSION: This technique offers a promising therapeutic alternative for the treatment of patients in refractory heart failure with cardiomyopathy and secondary mitral regurgitation.

Beta-adrenergic blocking agents in heart failure

Cardiac dysfunction in heart failure is widely recognized as a progressive process, regardless of the clinical signs and symptoms. An increase in cardiac sympathetic drive is one of the earliest neurohormonal responses occurring in patients with heart failure and may be one of the major causes of the progressive remodeling leading to the decline in myocardial function, and responsible for the poor prognosis of patients with heart failure. Therefore, recent data provided by several appropriately designed clinical trials clearly indicate the benefits of beta-adrenoceptor blocking agents, combined with diuretics, ACE inhibitors, and digoxin in chronic heart failure class II to IV due to systolic ventricular dysfunction. The benefits are related to symptoms, functional capacity, remodeling, and improvement in left ventricular function, reduction in cardiovascular hospitalization, a decrease in the overall and sudden cardiac death rate, and are similar in patients with ischemic or nonischemic cardiomyopathy, independent of age, gender, or functional class. In this review we describe the cardiovascular effects of the increase in sympathetic drive, the pharmacological properties of the beta-blockers most evaluated in heart failure therapy (metoprolol, bisoprolol, and carvedilol), the major clinical trials related to these agents in heart failure, the recommendations for their appropriate use in clinical practice, the precautions to be adopted, and how to handle the more common adverse reactions.

Echocardiographic assessment of the different left ventricular geometric patterns in hypertensive patients

OBJECTIVE: To identiy left ventricular geometric patterns in hypertensive patients on echocardiography, and to correlate those patterns with casual blood pressure measurements and with the parameters obtained on a 24-hour ambulatory blood pressure monitoring. METHODS: We studied sixty hypertensive patients, grouped according to the Joint National Committee stages of hypertension.. Using the single- and two-dimensional Doppler Echocardiography, we analyzed the left ventricular mass and the geometric patterns through the correlation of left ventricular mass index and relative wall thickness. On ambulatory blood pressure monitoring we assessed the means and pressure loads in the different geometric patterns detected on echocardiography RESULTS: We identified three left ventricular geometric patterns: 1) concentric hypertrophy, in 25% of the patients; 2) concentric remodeling, in 25%; and 3) normal geometry, in 50%. Casual systolic blood pressure was higher in the group with concentric hypertrophy than in the other groups (p=0.001). Mean systolic pressure in the 24h, daytime and nighttime periods was also higher in patients with concentric hypertrophy, as compared to the other groups (p=0.003, p=0.004 and p=0.007). Daytime systolic load and nighttime diastolic load were higher in patients with concentric hypertrophy ( p=0.004 and p=0.01, respectively). CONCLUSIONS: Left ventricular geometric patterns show significant correlation with casual systolic blood pressure, and with means and pressure loads on ambulatory blood pressure monitoring.

Reversibility of ventricular dysfunction: clinical experience in a medical office

OBJECTIVE - To describe clinical observations of marked improvement in ventricular dysfunction in a medical office environment under circumstances differing from those in study protocols and multicenter studies performed in hospital or with outpatient cohorts. METHODS - Eleven cardiac failure patients with marked ventricular dysfunction receiving treatment at a doctors office between 1994 and 1999 were studied. Their ages ranged from 20 and 66 years (mean 39.42±14.05 years); 7 patients were men, 4 were women. Cardiopathic etiologies were arterial hypertension in 5 patients, peripartum cardiomyopathy in 2, nondefined myocarditis in 2, and alcoholic cardiomyopathy in 4. Initial echocardiograms revealed left ventricular dilatation (average diastolic diameter, 69.45±8.15mm), reduced left ventricular ejection fraction (0.38±0.08) and left atrial dilatation (43.36±5.16mm). The therapeutic approach followed consisted of patient orientation, elimination of etiological or causal factors of cardiac failure, and prescription of digitalis, diuretics, and angiotensinconverting enzyme inhibitors. RESULTS - Following treatment, left ventricular ejection fraction changed to 0.63±0.09; left ventricular diameters changed to 57.18±8.13mm, and left atrium diameters changed to 37.27±8.05mm. Maximum improvement was noted after 16.9±8.63 (6 to 36) months. CONCLUSION - Patients with serious cardiac failure and ventricular dysfunction caused by hypertension, alcoholism, or myocarditis can experience marked improvement in ventricular dysfunction after undergoing appropriate therapy within the venue of the doctor's office.