The magnitude of early response to methotrexate therapy predicts long-term outcome of patients with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the relationship between the magnitude of clinical response in the first 6 months of methotrexate (MTX) therapy and long-term outcome in children with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts of 125 JIA patients who were started with MTX and then followed for at least 5 years were reviewed. Based on the level of American College of Rheumatology (ACR) Pediatric response at 6 months, patients were divided in four mutually exclusive groups: (1) non-responders, (2) responders at 30%, (3) responders at 50%, and (4) responders at 70%. The long-term outcome in each response group was evaluated by calculating the percentage change in active and restricted joint counts from baseline to 1, 2 and 5 years and the frequency of inactive disease at 5 years. RESULTS: At 6 months, 42 patients were classified as non-responders, 24 as 30% responders, 26 as 50% responders, and 33 as 70% responders. Patients who had achieved a 70% response showed a significantly greater percentage improvement in active joint count between baseline to 5 years compared with non-responders and 30% responders, and a significantly greater percentage improvement in restricted joint count between baseline to 5 years compared with 30% responders. The 70% responders also had a greater frequency of inactive disease at 5 years compared with 30% responders, CONCLUSIONS: Our results show that the achievement of an ACR Pediatric 70 response at 6 months after start of MTX therapy predicts a more favorable long-term outcome of patients with JIA.

Glycogen storage disease type II: clinical overview.

Glycogen storage disease type II has a broad continuous clinical spectrum in terms of onset, involvement of organs and life expectancy. Infantile onset is the most severe form, presenting with prominent cardiomyopathy, hypotonia, hepatomegaly and death before 12 months of life. Late onset form has onset at any age, lack of severe (or absence of) cardiac involvement, progressive skeletal muscle dysfunction and less dismal short-term prognosis. In addition to muscle and heart involvement, other tissues are affected liver, spleen, endothelium, lung, brain, anterior horns, peripheral nerves. In fact some patients with infantile form have hearing loss, abnormal brain myelination and central fever and some adult patients show aneurysms of brain arteries due to accumulation of glycogen in vessels. As for other treatable lysosomal diseases, the advent of enzyme replacement therapy will change the natural history of this disease and also will increase our knowledge concerning clinical heterogeneity.

Systemic lupus erythematosus-like disease in a 6-year-old boy with prolidase deficiency.

This report describes the case of a boy with prolidase deficiency who presented with splenomegaly and leg ulcers. Laboratory examination revealed hypergammaglobulinaemia, hyperimmunoglobulinaemia E, increased erythrocyte sedimentation rate, elevated transaminases, positive antinuclear and anti-double-stranded DNA antibodies, and complement consumption. No haematological, renal or articular problems were detected; neutrophil count was normal. The skin lesions were thought to be of vasculitic origin, and a diagnosis of systemic lupus erythematosus was made although the requirements for diagnosis of systemic lupus erythematosus based on American Rheumatism Association criteria were not satisfied. The child was treated with immunosuppressive drugs with worsening of skin lesions before the diagnosis of prolidase deficiency. Prolidase deficiency and systemic lupus erythematosus share a number of common immunological features and at least three patients with prolidase deficiency and immunological and clinical findings fulfilling the diagnostic criteria for systemic lupus erythematosus of the American Rheumatism Association are reported in the literature. Here we review pathogenetic hypothesis linking the metabolic defect to the disturbance in immune function. In particular we discuss the role of highly increased rates of apoptosis and/or abnormal processing of apoptotic keratinocytes in prolidase deficiency and the role of C1q deficiency, which is associated with the failure of normal clearance of apoptotic cells bearing on their surfaces many of the autoantigens involved in systemic lupus erythematosus.

[Deep vein thrombosis in the psychiatric patients under physical restraint].

Pulmonary thromboembolism induced by deep vein thrombosis (DVT), which is known as economy-class syndrome, is one of sudden death in psychiatric patients under physical restraint. (1) A decrease in venous blood flow, (2) damage to vessel walls, and (3) the enhancement of blood clotting are the major risk factors for DVT (Virchow triad). It has been speculated that physical restraint inhibits venous blood flow, and that antipsychotic drugs facilitate blood clotting. In order to prevent sudden death due to DVT, prophylactic measures and early diagnosis are crucial. Whereas Doppler ultrasonography and contrast venography are the gold standards for the diagnosis of DVT, more simplified methods are now under development. Of those, D-dimer measurement, which can be conducted with a small blood sample, is the most potent candidate for the biochemical diagnosis of DVT. Although there are many prophylactic measures, including anticoagulant medications and physical therapies, it is not clear which is the most effective and suitable in psychiatric practice. Psychiatric professionals should pay closer attention to DVT in psychiatric patients under physical restraint.

Roles of the vestibular system in controlling arterial pressure in conscious rats during a short period of microgravity.

In order to evaluate the roles of the vestibular system in controlling arterial pressure (AP) during exposure to a short period of microgravity (microG), the AP was measured in conscious free-moving rats having intact vestibular systems and those having vestibular lesions (FM-Intact and FM-VL groups, respectively). During free drop-induced microG, the AP increased in the FM-Intact group; it was 38+/-4 mmHg more than the AP observed during 1G. However, the increase in AP was significantly lower in the FM-VL group (20+/-2 mmHg). Further, to examine the sudden effect of a body floating in the midair in response to the AP during exposure to muG a body stabilizer was placed on the back of rats having intact vestibular systems and those having vestibular lesions (STAB-Intact and STAB-VL groups, respectively). The increase in the AP was significantly depressed in the STAB-Intact group; when compared with that in the FM-Intact group, but the increase was still significant (27+/-2 mmHg). On the other hand, the increase in the AP was completely eliminated in the STAB-VL group (7+/-5 mmHg). These results indicate that the AP increases during exposure to muG in conscious rats, and the vestibular system and body stability are significantly involved in this response.

Effects of high NaCl diet on arterial pressure in Sprague-Dawley rats with hepatic and sinoaortic denervation.

The Na(+) receptor that exists in the hepatoportal region plays an important role in postprandial natriuresis and the regulation of Na(+) balance during NaCl load. Thus it would be considered that a dysfunction of the hepatic Na(+) receptor might result in the elevation of arterial pressure under a condition of high NaCl diet. To elucidate this hypothesis, arterial pressure was continuously measured during three weeks of high NaCl diet (8% NaCl) in four groups of rats: (i) intact rats, (ii) rats with hepatic denervation (HD), (iii) rats with sinoaortic denervation (SAD), and (iv) rats with SAD+HD. During a 1-week normal NaCl diet period, there was no difference in arterial pressure among the four groups. A high NaCl diet had no influence on arterial pressure in intact or HD rats; however, it significantly increased by 11 +/- 3 mmHg in SAD rats. The addition of HD to SAD had no synergistic effect on arterial pressure; i.e., in SAD+HD rats, mean arterial pressure increased by 13 +/- 1 mmHg. In conclusion, sinoaortic baroreceptor, but not hepatic Na(+) receptor, has a significant role in the long-term regulation of arterial pressure on a high NaCl diet.

Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight.

To examine a hypothesis that change in regional blood flow due to decreased hydrostatic pressure gradient and redistribution of blood during reduced gravity (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and blood flow in the temporal muscle (MBF) with exposure to rG were measured in anesthetized rats in head-up tilt and flat positions during parabolic flight. Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal aortic pressure were also measured simultaneously. In the head-up tilt group, CBF increased by 15 +/- 3% within 3 s of entry into rG and rapidly recovered during rG. MBF also increased, but the change was significantly greater than that of CBF. JVP increased by 1.8 +/- 0.5 mmHg, probably due to loss of hydrostatic pressure gradient, since the measuring point of JVP was 2-3 cm above the hydrostatic indifference point. CAP and abdominal aortic pressure increased by 16.7 +/- 2 and 7.7 +/- 2 mmHg, respectively, compared with the 1-G condition. Muscle vascular resistance [(CAP-JVP)/MBF] decreased on entry into rG, but no significant change was observed in cerebrocortical vascular resistance [(CAP-JVP)/CBF]. In the flat group, no significant change was observed in all the variables. The results indicate that arteriolar vasodilatation occurs in the temporal muscle but not in the cerebral cortex. Thus the blood flow control mechanism at the onset of rG is different between intra- and extracranial organs.

Controlling arterial blood pressure using a computer-brain interface.

There has been recent interest in the concept of connecting a computer to the brain to control brain functions. However, there are challenges that must be overcome in developing such a computer-brain interface, including a selection of nucleus that is stimulated, and an implantable electrode and electrical stimulator. Another important issue is the designing of the controller, that is, determining how to encode as an electrical signal the information to be sent to the brain. We have applied system identification theory, a method for evaluating dynamic characteristics of a system, to the arterial blood pressure control system of the brain. Our results show that (1) the stimulation-arterial blood pressure response relationship can be described as a mathematical model, which gives a good prediction of the arterial blood pressure response, facilitating the designing of a computer-brain interface, and (2) the arterial blood pressure can be actually controlled using a computer-brain interface.

Sequence of forebrain activation induced by intraventricular injection of hypertonic NaCl detected by Mn2+ contrasted T1-weighted MRI.

In order to define the sequence of forebrain activation involved in osmoregulation, central activation in response to intracerebroventricular injection of NaCl solution (10 microl of 0.15, 0.5, or 1.5 M) was detected using manganese-contrasted magnetic resonance imaging (MRI) in anesthetized rats. Changes in renal sympathetic nerve activity (RNA) were also measured, and the time courses of forebrain activation and RNA changes compared. NaCl injection resulted in rapid activation of the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), and periventricular regions and the lateral hypothalamic area (LHA), then of the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON). The delay in activation in the PVN and SON showed a wide variation from 0 to 5.78 min, and the average delay in the PVN (2.88+/-0.34 min) and SON (2.90+/-0.39 min) was significantly greater than that in the SFO (0.40+/-0.10 min) and OVLT (0.74+/-0.13 min). NaCl (1.5 M) injection elicited a rapid, large increase in RNA, which consisted of two components, an early rapid increase at 99 s after injection (160+/-27%) and a slower increase at 9 min after injection (209+/-34%). These results suggest that the PVN and SON are activated not only by the afferent input from the SFO and OVLT but also by diffusion of the hypertonic stimulus to these regions and probably by their intrinsic osmosensitivity. The PVN might be responsible for the second slower component of the RNA response, but cannot be responsible for the first component.

R-R interval variability with lower body positive pressure assessed by wavelet packet transform.

Lower body positive pressure (LBPP) is used for simulation of microgravity due to central fluid shift. In the present study, we evaluate R-R interval variability, which is sometimes considered as an index of human cardiovascular autonomic nerve status. 10 healthy male subjects were set in a chamber with standing position. Chamber pressure was raised 10 mmHg each for every 3 minutes, up to +40 mmHg. Wavelet packet transform (WPT) followed by Hilbert transform was employed to analyze time-dependent changes in low frequency component (LF) and high frequency component (HF) of R-R interval variability. Calf circumference lowered according to chamber pressure. ABP was maintained throughout measurements. R-R interval was significantly higher at +30 and +40 mmHg compared to that of control. Standing LBPP causes higher HF and lower L/H probably due to central fluid shift, and WPT followed by Hilbert transform shows time-dependent changes in R-R interval variability.

Skin blood flow with elastic compressive extravehicular activity space suit.

During extravehicular activity (EVA), current space suits are pressurized with 100% oxygen at approximately 222 mmHg. A tight elastic garment, or mechanical counter pressure (MCP) suit that generates pressure by compression, may have several advantages over current space suit technology. In this study, we investigated local microcirculatory effects produced with negative ambient pressure with an MCP sleeve. The MCP glove and sleeve generated pressures similar to the current space suit. MCP remained constant during negative pressure due to unchanged elasticity of the material. Decreased skin capillary blood flow and temperature during MCP compression was counteracted by greater negative pressure or a smaller pressure differential.