Fibrose pulmonaire idiopathique: nouveautés diagnostiques et thérapeutiques [Idiopathic pulmonary fibrosis: recent diagnostic and therapeutic advances].

Idiopathic pulmonary fibrosis (IPF) is the most frequent of the idiopathic interstitial pneumonias. It is a progressive disorderwith a poor prognosis. Its diagnosis requires the careful exclusion of potential causes, and a pattern of usual interstitial pneumonia at high-resolution computed tomography or video-assisted surgical lung biopsy. Several recent randomized trials have profoundly modified the therapeutic management of IPF. The combination of prednisone and azathioprine, often prescribed until recently, has been shown to be harmful and is no longer indicated. N-acetylcystein, also used in the past decade, failed to show an efficacy. However, two new antifibrotic drugs, pirfenidone and nintedanib, have for the first time proven effective in slowing disease progression.

Crescimento inicial do cafeeiro Rubi em resposta a doses de nitrogênio, fósforo e potássio e a regimes hídricos

O objetivo deste trabalho foi avaliar o crescimento da parte aérea do cafeeiro (Coffea arabica L.) cultivar Rubi MG 1192 submetido a três doses de N, P e K e dois regimes hídricos durante o primeiro ano após o transplante, em 20 de novembro de 2000. O crescimento da planta foi avaliado aos 134, 196, 236, 284, 334 e 383 dias após o transplante (dat). Houve resposta ao N e ao K no crescimento em número de ramos plagiotrópicos por planta, ao passo que no número de nós com gemas por planta, observou-se resposta apenas ao nitrogênio. Não houve resposta ao N, P e K no aumento da massa seca da parte aérea e no índice de área foliar. Além de mostrar efeito significativo no crescimento do cafeeiro, a irrigação antecipou o rápido crescimento para julho (236 dat) proporcionando plantas mais vigorosas. Nas plantas não-irrigadas, o rápido crescimento ocorreu em meados de outubro (334 dat). Entretanto, a irrigação não impediu a queda na taxa de crescimento durante o inverno. O desenvolvimento das gemas em frutos ou ramos secundários nas plantas não-irrigadas alterou a distribuição de matéria seca e reduziu o crescimento do caule, ramos e folhas.

Atypical Kawasaki disease with peripheral gangrene and myocardial infarction: therapeutic implications.

We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to gangrene is a rare but serious complication of KD in infants younger than 7 months of age. Treatment has been targeted at reducing arterial inflammation, arteriospasm and thrombosis. We report the first patient with incomplete KD and peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating and antithrombotic agent appeared successful, restoring hand and foot perfusion without significant long-term sequelae. However, PGE1 could have supported development of myocardial infarction by shunting blood away from ischaemic areas distal to a giant coronary artery aneurysm with beginning thrombosis. CONCLUSION. Atypical KD with peripheral gangrene appears to react favourably to treatment with PGE1, but needs careful monitoring to detect early signs of cardiac ischaemia.

Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance.

Therapeutic drug monitoring (TDM) and pharmacogenetic tests play a major role in minimising adverse drug reactions and enhancing optimal therapeutic response. The response to medication varies greatly between individuals, according to genetic constitution, age, sex, co-morbidities, environmental factors including diet and lifestyle (e.g. smoking and alcohol intake), and drug-related factors such as pharmacokinetic or pharmacodynamic drug-drug interactions. Most adverse drug reactions are type A reactions, i.e. plasma-level dependent, and represent one of the major causes of hospitalisation, in some cases leading to death. However, they may be avoidable to some extent if pharmacokinetic and pharmacogenetic factors are taken into consideration. This article provides a review of the literature and describes how to apply and interpret TDM and certain pharmacogenetic tests and is illustrated by case reports. An algorithm on the use of TDM and pharmacogenetic tests to help characterise adverse drug reactions is also presented. Although, in the scientific community, differences in drug response are increasingly recognised, there is an urgent need to translate this knowledge into clinical recommendations. Databases on drug-drug interactions and the impact of pharmacogenetic polymorphisms and adverse drug reaction information systems will be helpful to guide clinicians in individualised treatment choices.

Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update

Captopril, an orally active angiotensin-converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long-term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin-angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.

Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy

BACKGROUND : Status epilepticus (SE) treatment ranges from small benzodiazepine doses to coma induction. For some SE subgroups, it is unclear how the risk of an aggressive therapeutic approach balances with outcome improvement. We recently developed a prognostic score (Status Epilepticus Severity Score, STESS), relying on four outcome predictors (age, history of seizures, seizure type and extent of consciousness impairment), determined before treatment institution. Our aim was to assess whether the score might have a role in the treatment strategy choice. METHODS : This cohort study involved adult patients in three centers. For each patient, the STESS was calculated before primary outcome assessment: survival vs. death at discharge. Its ability to predict survival was estimated through the negative predictive value for mortality (NPV). Stratified odds ratios (OR) for mortality were calculated considering coma induction as exposure; strata were defined by the STESS level. RESULTS : In the observed 154 patients, the STESS had an excellent negative predictive value (0.97). A favorable STESS was highly related to survival (P < 0.001), and to return to baseline clinical condition in survivors (P < 0.001). The combined Mantel-Haenszel OR for mortality in patients stratified after coma induction and their STESS was 1.5 (95 % CI: 0.59-3.83). CONCLUSION : The STESS reliably identifies SE patients who will survive. Early aggressive treatment could not be routinely warranted in patients with a favorable STESS, who will almost certainly survive their SE episode. A randomized trial using this score would be needed to confirm this hypothesis.

Doses e épocas de aplicação de nitrogênio no feijoeiro irrigado cultivado em plantio direto

O nitrogênio é o nutriente exigido em maiores quantidades pela cultura do feijão. A resposta à sua aplicação depende da dose aplicada e da época de sua aplicação. O objetivo deste trabalho foi avaliar os componentes de produção, produtividade de grãos e a qualidade fisiológica de sementes de feijão, decorrentes de diferentes doses de N (uréia) aplicadas em cobertura em três estádios da cultura. O experimento foi conduzido no sistema plantio direto. Os tratamentos foram constituídos por 0, 40, 80, 120,160, 200 e 240 kg ha-1 de N aplicados em cobertura nos estádios V4-5, R5 e R6, correspondendo, respectivamente, a 21, 32 e 38 dias após a emergência das plantas. A qualidade fisiológica de sementes foi avaliada por meio do teste de germinação e testes de vigor. O N aplicado nas diferentes fases da cultura não interferiu nos componentes de produção. A máxima produtividade de grãos foi obtida com 164 kg ha-1 de N em cobertura, independentemente do estádio de desenvolvimento. A qualidade fisiológica das sementes não foi influenciada pelos tratamentos.

Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM.

Potentiation of glucose-induced insulin secretion by intestinal factors has been described for many years. Today, two major peptides with potent insulinotropic action have been recognized: gastric inhibitory peptide and truncated forms of glucagon-like peptide I, GLP-I(7-37) or the related GLP-I(7-36)amide. These hormones have specific beta-cell receptors that are coupled to production of cAMP and activation of cAMP-dependent protein kinase. Elevation in intracellular cAMP levels is required to mediate the glucoincretin effect of these hormones: the potentiation of insulin secretion in the presence of stimulatory concentrations of glucose. In addition, circulating glucoincretins maintain basal levels of cAMP, which are necessary to keep beta-cells in a glucose-competent state. Interactions between glucoincretin signaling and glucose-induced insulin secretion may result from the phosphorylation of key elements of the glucose signaling pathway by cAMP-dependent protein kinase. These include the ATP-dependent K+ channel, the Ca++ channel, or elements of the secretory machinery itself. In NIDDM, the glucoincretin effect is reduced. However, basal or stimulated gastric inhibitory peptide and glucagon-like peptide I levels are normal or even elevated, suggesting that signals induced by these hormones on the beta-cells are probably altered. At pharmacological doses, infusion of glucagon-like peptide I but not gastric inhibitory peptide, can ameliorate postprandial insulin secretory response in NIDDM patients. Agonists of the glucagon-like peptide I receptor have been proposed as new therapeutic agents in NIDDM.

Dessecação pré-colheita de soja e Brachiaria brizantha consorciadas com doses reduzidas de graminicida

O objetivo deste trabalho foi avaliar os efeitos da dessecação pré-colheita de soja consorciada com Brachiaria brizantha cv. Marandu, com doses reduzidas de graminicida, na viabilização de colheita mecânica de soja e na capacidade de rebrota e formação de palha de B. brizantha. Foi utilizado esquema fatorial 5x3, com cinco doses do graminicida fluazifop-p-butil - 0, 15, 30, 45 e 60 g ha-1 - e três manejos de dessecação do consórcio - sem dessecação e com dessecação nos estádios R7 ou R8 da soja -, em delineamento de blocos casualizados, com quatro repetições. Foram avaliadas duas testemunhas, soja e B. brizantha em monocultivo, capinadas manualmente. A braquiária foi altamente suscetível à ação do graminicida. O consórcio entre soja e B. brizantha, submetido a 15 g ha-1 de graminicida e dessecado no estádio R7 da soja, permitiu a colheita mecânica da soja e a produção de grãos semelhante à alcançada no monocultivo, proporcionando acúmulo de matéria seca de B. brizantha de 4,6 t ha-1, 60 dias depois da colheita da soja. A B. brizantha consorciada com soja, sem aplicação de graminicida, acumulou 6 t ha-1 de matéria seca na colheita da soja e 9,3 t ha-1 60 dias depois da colheita da soja, e o acúmulo de matéria seca de B. brizantha em monocultivo, nessas duas épocas, foi de 13,3 e 21,6 t ha-1, respectivamente.

Influence of triamcinolone intravitreal injection on retinochoroidal healing processes.

To analyze the effects of triamcinolone intravitreal injection on the wound healing processes after argon laser retinal photocoagulation, wild type C57BL/6J mice, 8-12 weeks old underwent a standard argon laser photocoagulation protocol. After pentobarbital anesthesia and pupil dilatation, argon laser lesions were induced (50microm, 400mW, 0.05s). Two photocoagulation impacts created two disc diameters from the optic nerve in both eyes. The photocoagulated mice were divided into four groups: Group I (n=12), photocoagulation controls, did not receive any intravitreous injection. Group II (n=12), received an intravitreous injection of 1microl of balanced salt solution (BSS). Group III (n=12), received an intravitreous injection of 1microl containing 15microg of triamcinolone acetonide (TAAC) in BSS. Two mice from each of these three groups were sacrificed at 1, 3, 7, 14 days and 2 and 4 months after photocoagulation. Group IV (n=10) received 1.5, 3, 7.5, 15, or 30microg of TAAC and were all sacrificed on day 14. The enucleated eyes were subjected to systematic analysis of the cellular remodeling processes taking place within the laser lesion and its vicinity. To this purpose, specific antibodies against GFAP, von Willebrand factor, F4/80 and KI67 were used for the detection of astrocytes, activated Müller cells, vascular endothelial cells, infiltrating inflammatory cells and actively proliferating cells. TUNEL reaction was also carried out along with nuclear DAPI staining. Temporal and spatial observations of the created photocoagulation lesions demonstrate that 24h following the argon laser beam, a localized and well-delineated affection of the RPE cells and choroid is observed in mice in Groups I and II. The inner retinal layers in these mice eyes are preserved while TUNEL positive (apoptotic) cells are observed at the retinal outer nuclear layer level. At this stage, intense staining with GFAP is associated with activated retinal astrocytes and Müller cells throughout the laser path. From day 3 after photocoagulation, dilated new choroidal capillaries are detected on the edges of the laser lesion. These processes are accompanied by infiltration of inflammatory cells and the presence of proliferating cells within the lesion site. Mice in Group III treated with 15microg/mul of triamcinolone showed a decreased number of infiltrating inflammatory cells and proliferating cells, which was not statistically significant compared to uninjected laser treated controls. The development of new choroidal capillaries on the edges of the laser lesion was also inhibited during the first 2 months after photocoagulation. However, on month 4 the growth of new vessels was observed in these mice treated with TAAC. Mice of Group IV did not show any development of new capillaries even with small doses. After argon laser photocoagulation of the mouse eye, intravitreal injection of triamcinolone markedly influenced the retina and choroid remodeling and healing processes. Triamcinolone is a powerful inhibitor of the formation of neovessels in this model. However, this inhibition is transient. These observations should provide a practical insight for the mode of TAAC use in patients with wet AMD.