Kawasaki disease triggered by parvovirus infection: an atypical case report of two siblings.

BACKGROUND: There are reports of the familial occurrence of Kawasaki disease but only a few reports described Kawasaki disease in siblings. However, the familial cases were not simultaneous. In these patients the idea of infective agents as trigger must be considered. CASE PRESENTATION: We describe two siblings with atypical presentations of Kawasaki disease; the sister was first diagnosed as having parvovirus infection with anemia and the brother was diagnosed as having myocarditis. The first patient was a 9-month-old Caucasian girl with fever, conjunctivitis, rash, and pharyngitis, and later she had cervical adenopathy, diarrhea and vomiting, leukocytosis, and anemia, which were explained by positive immunoglobulin M against parvovirus. However, coronary artery lesions with aneurysms were documented at day 26 after fever onset. An infusion of intravenous immunoglobulin and high doses of steroids were not efficacious to resolve the coronary lesions. She was treated with anakinra, despite a laboratory test not showing inflammation, with prompt and progressive improvement of coronary lesions. Her 7-year-old Caucasian brother presented vomiting and fever at the same time as she was unwell, which spontaneously resolved after 4 days. Four days later, he again presented with fever with abdominal pain, associated with tachypnea, stasis at the pulmonary bases, tachycardia, gallop rhythm, hypotension, secondary anuria, and hepatomegaly. An echocardiogram revealed a severe hypokinesia, with a severe reduction of the ejection fraction (20%). He had an increase of immunoglobulin M anti-parvovirus, tested for the index case of his sister, confirming the suspicion of viral myocarditis. He received dopamine, dobutamine, furosemide plus steroids, with a progressive increase of the ejection fraction to 50%. However, evaluating his sister's history, the brother showed a myocardial dysfunction secondary to Kawasaki shock syndrome. CONCLUSIONS: We report on familial Kawasaki disease in two siblings which had the same infectious trigger (a documented parvovirus infection). The brother was diagnosed as having post-viral myocarditis. However, in view of the two different and simultaneous evolutions, the girl showed Kawasaki disease with late coronary artery lesions and aneurysms, whereas the brother showed Kawasaki shock syndrome with myocardial dysfunction. We stress the effectiveness of anakinra in non-responder Kawasaki disease and the efficacy on coronary aneurysms.

Clinically relevant pleiotropic effects of statins: drug properties or effects of profound cholesterol reduction?

Clinical trials have firmly established that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) can induce the regression of vascular atherosclerosis and reduce cardiovascular-related morbidity and death in patients with and without coronary artery disease. It is usually assumed that these beneficial effects are due to the ability of statins to reduce cholesterol synthesis. However, because mevalonic acid is not only the precursor of cholesterol but also of many non-steroidal isoprenoid compounds, the inhibition of HMG-CoA reductase may lead to pleiotropic effects. As shown by the data reported in this review, some statins can interfere with major events involved in the formation of atherosclerotic lesions, regardless of their hypolipidemic properties. The relevance of these effects in humans remains to be established (particularly in view of the high statin doses required to produce a direct vascular action), thus their contribution to the reduction in cardiovascular events observed in clinical trials has become one of the major challenges for future studies aimed at clarifying the anti-atherosclerotic benefits of statins.

Upregulation and activation of Stat6 precede vascular smooth muscle cell proliferation in carotid artery injury model.

The role of signal transducers and activators of transcription (STAT) proteins in modulating proliferation and differentiation of various cell types in the hematopoietic system and the central nervous system has been well established. In contrast, the pathophysiological role of these proteins in vascular proliferative diseases has remained unproven, despite in vitro observations emphasizing the involvement of the STAT system in mediating vascular smooth muscle cell (VSMC) proliferation. On the basis of our previous observations demonstrating the occurrence of a specific modulation of Stat6 protein during the proliferative, migratory, and differentiation phases of the developing brain, we investigated whether Stat6 protein is present and modulated in arterial tissue challenged by perivascular injury. The time course of expression and localization of Stat6 after arterial injury was analyzed by immunohistochemistry, Western blot analysis, and confocal microscopy. Six hours after injury, the expression of Stat6 was markedly increased. This overexpression preceded the onset of VSMC proliferation and was downregulated starting from 7 days after injury, coincident with the decline of VSMC proliferation. Moreover, early after injury, Stat6 was predominantly localized at the nuclear level, denoting its functional activation. Conversely, Stat6 staining at later time points was largely cytosolic, suggesting silencing effects of this signaling pathway. These data indicate that Stat6 signaling may contribute to the modifications of gene expression underlying VSMC activation in the context of acute vascular proliferative diseases.

Diabetes gestacional: evaluación de un nuevo método diagnóstico / Pregnancy diabetes: evaluation of a new diagnosis method

La diabetes gestacional es la alteración del metabolismo de los hidratos de carbono durante el embarazo que puede revertirse o no en el puerperio. Se efectuó un estudio retrospectivo a fin de evaluar el nuevo método de diagnóstico de Diabetes Gestacional, consistente en la prueba de tolerancia a la glucosa previa ingesta de 75 gr. de la misma. Se evaluaron las pruebas realizadas entre los meses de enero y julio de 1999. El total fue de 376 pruebas, de las cuales 27 fueron patológicas (7,18 por ciento), donde el grupo etario de mayor prevalencia fue entre 30 y 40 años(55,55 por ciento) el porcentaje de cesárea fue el 25,9 por ciento con un 84,6 por ciento, se manejaron con dieta y la incidencia de macrosomía fetal de un 18,5 por ciento. Se analizaron los valores obtenidos entre 130-140 mg/dl donde se obtuvo un total de 12 casos (3,19 por ciento), con resultado de macrosomía fetal de un 25 por ciento. También se evaluaron las pruebas con valores menores a 130 mg/dl hallándose un número de 337 (90,10 por ciento con una incidencia de macrosomía de 11.57 por ciento. Concluimos que este método no debería realizarse a pacientes menores de 20 años sin factores de riesgo, y si el punto de corte para diagnóstico de Diabetes Gestacional no deberá ser menor al estipulado actualmente (140 mg por ciento) dado el índice de macrosomía mayor encontrado con glucemias superiores a 130 mg por ciento. Se necesitarían estudios multicéntricos nacionales a fin de avalar esta conclusión

Effect of lercanidipine and its (R)-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits.

The in vivo antiatherogenic activity of the calcium antagonist lercanidipine and its (R)-enantiomer was investigated in two different types of atherosclerotic lesions (hyperplastic and fatty-streak lesions) in rabbits. Lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) as well as its (R)-enantiomer at 3 mg kg(-1) week(-1) were given by subcutaneous injection for 10 weeks to White New Zealand rabbits, with cholesterol feeding beginning at week 2. The hyperplastic lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty streak lesions were induced by cholesterol feeding. In untreated animals (n=5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries without collar showed a intima/media (I/M) ratio of 0.03+/-0.02, whereas in carotids with a collar the ratio was 2+/-0.42. In lercanidipine-treated animals a significant and dose-dependent effect on intimal hyperplasia was observed. I/M ratios were 0.73+/-0.4, 0.42+/-0.1, 0.32+/-0.1 for 0.3, 1, and 3 mg kg(-1) week(-1), respectively (P<0.05). The lercanidipine enantiomer (3 mg kg(-1) week(-1)) was as effective as the racemate (0.41+/-0.11). Proliferation of smooth muscle cells, assessed by incorporation of BrdU into DNA, was reduced by about 50%, 70%, 85%, and 80% by lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) and its (R)-enantiomer, respectively. The area of fatty-streaks in the aorta (n = 11-15) was significantly reduced by lercanidipine (3 mg kg(-1) week(-1), 16% vs 27%, P<0.05), a trend was observed also with lower doses. When different segments of the aorta were considered (arch, thoracic, abdominal) a significant and dose-dependent effect in the thoracic and abdominal aorta was observed also at lower doses. The (R)-enantiomer was as effective as lercanidipine. These results suggest a direct antiatherosclerotic effect of lercanidipine, independent of modulation of risk factors such as hypercholesterolemia and/or hypertension as demonstrated by the absence of stereoselectivity.

Proapoptotic effect of atorvastatin on stimulated rabbit smooth muscle cells.

The in vitro and in vivo activity of atorvastatin and other 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (fluvastatin, pravastatin and simvastatin) has been investigated. Atorvastatin, fluvastatin, pravastatin and simvastatin caused a significant and dose-dependent (0.1-50 microM) reduction in cell multiplication of vascular smooth muscle cells (SMC) in cultures associated with the retardation of cycling cells in the G1 and G2/M compartments at 24 h, a phenomenon leading to apoptosis (programmed cell death) in several experimental in vitro models. The effects on the cell cycle resulted in a strong inhibition of cell proliferation at 48 h, followed by apoptosis when incubation was prolonged to 72 h as assessed by nuclei morphology and cytofluorimetric analysis of DNA. The apoptotic effect observed for the statins is completely prevented by the addition of exogenous mevalonate at a 100 microm concentration. in vivo SMC proliferation was stimulated by applying a silastic collar to the outside surface of carotid arteries in normocholesterolemic rabbits in the presence of an anatomically intact endothelium. The positioning of the collar promoted apoptosis in control vessels as assessed by Terminal Deoxynucleotidyl Transferase-dUTP-Biotin Nick-End Labeling (TUNEL) assay. The pre-treatment with 5 mg kg-1 per day of atorvastatin before collar insertion strongly increased the number of TUNEL-positive cells, suggesting a pro-apoptotic effect of HMGCoA reductase inhibitors also in vivo, even though cell DNA rearrangement still needs to be excluded. No apoptotic signal was detectable in sham operated arteries with no collar in either control or atorvastatin-treated rabbits. These data indicate that HMGCoA reductase inhibitors effect on the arterial wall may involve the modulation of both cell proliferation and programmed cell deaths supporting a possible role of statins in the prevention of early lesion and restenosis.

Systolic anterior motion of the mitral valve in patients with hypertrophic cardiomyopathy. Disappearance after treatment with amiodarone.

We used amiodarone as the only drug in three consecutive patients with hypertrophic cardiomyopathy, marked systolic anterior motion of the mitral valve on M-mode echocardiogram, and paroxysmal atrial fibrillation. The effective control of atrial fibrillation was associated with good symptomatic relief and with reduction until disappearance of the systolic anterior motion of the mitral valve. These data were confirmed in a follow-up of 46, 30 and 30 months.

[Prognostic value of echocardiographic finding of valvular vegetations in patients with infectious endocarditis]. / II valore prognostico del rilievo ecocardiografico di vegetazioni valvolari in pazienti con endocardite infettiva.

42 consecutive patients with infective endocarditis on native valves, according to Pelletier and Petersdorf's criteria of definite (13 pts), probable (12 pts.) and possible (17 pts) endocarditis, were identified and prospectively followed-up with M-mode and two-dimensional echocardiography, since 1980. We compared: 1) these three groups; 2) survivors not referred for surgery versus surgical patients plus nonsurvivors; 3) patients who suffered embolic events versus those who did not; 4) patients with severe-moderate heart failure versus those with no failure or mild failure; 5) patients with aortic valve echocardiographic vegetations versus those with mitral valve vegetations. Furthermore 11 of these patients who did not undergo surgery (9 with mitral and 2 with mitro-aortic vegetations on echo) were serially followed-up with echocardiography for 6-42 months (average: 32 months). The presence of ultrasound detectable vegetations itself and their size, without considering their site, did not identify a major risk of embolization, heart failure, death or need of surgery. The site of vegetations was the only significant feature in our series. It identified a high-risk group and a relatively low-risk group. Aortic valve involvement, with echocardiographic vegetations, was related to severe or moderate heart failure (P less than 0.01), death or need of surgery (P less than 0.05). Mitral valve involvement carried on a relatively low risk. The 9 patients with mitral valve vegetations only, not referred for surgery and followed-up, did well on medical treatment and returned to work. They did not have relapses or embolization. On serial echocardiographic examinations, mitral vegetations become smaller in the long run. Two years after the acute episode, usually echocardiography did not allow identification of vegetations.