Renal artery clipping attenuates the progression of adriamycin nephropathy

This study was designed to analyze the impact of diminished renal perfusion pressure due to renal clipping on the rat model of adriamycin nephropathy. Male Wistar rats, divided into four groups (n = 9 per group) were injected with saline as control (C), adriamycin 3 ml/kg (Ad), saline with the left renal artery clipped (Rv), and adriamycin plus clip (AdRv). After 24 weeks mean arterial pressure (MAP), inulin, and p-aminohippurate (PAH) clearances were performed to evaluate renal function. Morphologic analysis included histologic criteria of percentage of glomerulosclerosis and tubulointerstitial lesion index (TILI). The MAP (mm Hg) was similar between Rv (143 +/- 13) and AdRv (154 +/- 20), but higher (P < .05) than C (120 +/- 8) and Ad (124 +/- 11). Inulin clearance (mL/min/100 g) in Ad (0.2 +/- 0.05) was smaller than in C (0.53 +/- 0.17) and Rv (0.4 +/- 0.01) (P < .05), and was at an intermediate level in AdRv (0.33 +/- 0.2). The level of PAH (mL/min/100 g) was normal at 1.76 in C, and diminished more in Ad (0.58) than in Rv (1.06) and AdRv (1.18) (P < .05). Both Ad and the AdRv nonclipped kidneys had the highest degree of glomerulosclerosis (33% and 25%) and TILI (7% and 8%), respectively, compared with C and Rv (both 0%), whereas the clipped kidneys displayed intermediate degrees (9% and 5%) (P < .05 v nonclipped). The data suggest that diminished perfusion pressure of the clipped kidney, by decreasing the intraglomerular pressure, protects the glomerulus from damage and attenuates the evolution of adriamycin nephropathy. Am J Hypertens 1998;11:1124-1128 (C) 1998 American Journal of Hypertension, Ltd.

Proxy-reported health-related quality of life of patients with juvenile idiopathic arthritis: Pediatric rheumatology international trials organization multinational quality of life cohort study

Objective. To investigate the proxy-reported health-related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).Methods. In this multinational, multicenter, cross-sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.Results. A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 +/- 10.6 versus 54.6 +/- 4.0, P < 0.0001; psychosocial: 47.6 +/- 8.7 versus 51.9 +/- 7.59 P < 0.0001), with the physical well-being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score > 1 and a pain intensity rating > 3.4 cm on a 10-cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.Conclusion. We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well-being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.

Growth and juvenile development of Uca maracoani Latreille 1802-1803 in laboratory conditions (Crustacea, Decapoda, Brachyura, Ocypodidae).

The life cycle of decapod crustaceans can be classified into three distinct morphological phases: larval, juvenile and adult. Despite its recognized importance, studies of the juvenile phase have been neglected. The present Study aimed to analyze the growth of juveniles from a single population of Uca maracoani under laboratory conditions, and also to describe the morphological differentiation of pleopods in each sex. Megalopae and juvenile crabs or U. maracoani obtained on a Mud beach at Jabaquara, Paraty, on the southern coast of the state of Rio de Janeiro (Brazil), were reared in the laboratory. The specimens were checked daily for molts and deaths. The carapace widths (CW) of intact exuviae and dead individuals were measured under a stereoscopic microscope provided with a micrometer rule. These data allowed the definition of a growth equation as well as the stages related to the beginning of pleopod development, which begins when females reach 3.0 mill CW (6th juvenile developmental stage), similar to the sizes reported for other species of the genus. In males, however, pleopods appear when the crabs reach 3.5 mm CW, equivalent to the 7th developmental stage. This difference may be related to differential growth between sexes. It also may be a consequence of laboratory rearing, or may represent an actual feature of the species.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis

ObjectiveTo compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America.MethodsPatients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course.ResultsFour hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron's papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians.ConclusionThe demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

Effects of ambient colour on colour preference and growth of juvenile rainbow trout Oncorhynchus mykiss (Walbaum)

Colour preference of individual juvenile rainbow trout Oncorhynchus mykiss was tested at 1 and 12 degrees C, and also at 12 degrees C after a 42 day growth experiment under white, blue, green, yellow or red ambient colour. All experiments were carried out under controlled laboratory conditions and the preference was assessed by the location of the fish in a preference tank with four chambers. Rainbow trout showed a preference for blue and green at 1 degrees C and for green at 12 degrees C. After the growth experiment the fish reared in blue tanks preferred blue and green but green was the most preferred colour for the fish reared in green, yellow and red tanks. Yellow and especially red chambers were avoided, irrespective of the ambient colour during the growth trial. The final mass of fish reared in the red aquaria was significantly smaller than that of the fish in green tanks. In addition, when the data of the preference tests were correlated with the data of the growth experiment using mean values of the four tested colours, a very good linear relationship was observed between the preference (i.e. visit frequency in coloured compartments) and growth rate as well as food intake. When considering the results both from the preference and growth trials it is suggested that green is the best environmental colour for rearing juvenile rainbow trout while rearing in a red environment cannot be recommended. (c) 2008 The Authors Journal compilation (c) 2008 The Fisheries Society of the British Isles.

Longer wavelengths of light improve the growth, intake and feed efficiency of individually reared juvenile pikeperch Sander lucioperca (L.)

We tested the effects of monochromatic light on the specific growth rate (SGR), feed intake and feed efficiency (FE) of juvenile pikeperch, Sander lucioperca (L.). Pikeperch were reared individually for 42 days in aquaria covered with blue, green, yellow or red gelatin filters or white paper (control; n=5). Linear regression analysis indicated a significant positive effect of longer wavelengths of light on the condition factor (CF), FE and SGR. The final weight, SGR and CF were significantly higher in fish reared under red than under white light, and FE was better under green, yellow and red light than under white light (Dunnett's post hoc test, P < 0.05) while blue was comparable to white light in terms of the measured parameters. After the growth trial, the spectral sensitivity of photoreceptor cells in the retina was tested using microspectrophotometry, which revealed the presence of rods with lambda(max) at ca. 530 nm and two cone classes, absorbing maximally at ca. 535 and 603 nm, all containing a porphyropsin-based pigment. These results suggest that the presence of mid and long wavelength-sensitive cones enhances visual sensitivity under mid-wavelength and long-wavelength environments, and thus supports the finding that longer wavelengths of incoming light can improve FE and SGR of the cultivated pikeperch.

Long-Term Outcome and Prognostic Factors of Juvenile Dermatomyositis: A Multinational, Multicenter Study of 490 Patients

Objective. To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study.Methods. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL).Results. A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%.Conclusion. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb.

ANALISE FAMILIAL DO COMPORTAMENTO IN VITRO DOS MACROFAGOS HUMANOS FRENTE AO MYCOBACTERIUM LEPRAE

The lysogenic capacity of human macrophages facing M. leprae in vitro may be dependent on an important genetic component. Although the familial aggregation of the trait is demonstrated, this is a necessary but not sufficient condition to prove genetic influence. The data do not fit some simple genetic models (autosomal dominant or incompletely dominant gene; dominant or recessive sex-linked gene). The results obtained are consistent with the hypothesis that the macrophages' lysogenic capacity is mainly due to a major gene with variable expressivity. This hypothesis may be too simple to account for the whole variability detected and therefore must be considered a working hypothesis.

The hemolytic uremic syndrome as a complication of adriamycin nephropathy

Rats treated with two injections of adriamycin (week 0 and week 12) developed glomerusclerosis and severe tubulointerstitial lesions as described in the literature. In addition, a number of glomerular alterations were present. These included capillary loop dilation, insudation of eosinophilic material, necrosis, duplication of the glomerular basement membrane, severe mesangiolysis with disruption of the mesangial matrix and segmental double- contours. The renal arterioles and interlobular arteries showed endothelial cell swelling. The subendothelial space was infiltrated by fibrinoid material and there was intensive fibrinoid necrosis of the wall of both arteries and arterioles extending into the glomerular tuft. These alterations were very similar to those observed in the hemolytic uremic syndrome. This observation suggests that the two injections of adriamycin, with a long interval in between them, might induce renal lesions similar to those observed in the hemolytic uremic syndrome.

Effects of cyclosporine on adriamycin induced nephropathy

The effect of cyclosporine on adriamycin nephropathy was studied over both short (6 weeks) and long (26 weeks) periods. In the short-term study, cyclosporine was introduced 2 weeks after nephritis induction and in the long-term study, 14 weeks after the first adriamycin injection. The animals with adriamycin nephropathy treated with cyclosporine, studied for 6 weeks, developed proteinuria with increased renal size and glomerular area. The nephrotic animals treated with cyclosporine showed less proteinuria than the nephrotic control animals. There were no differences in glomerular area, creatinine clearance or serum creatinine and kidney weight between the treated nephrotic group and the health control group. The nephrotic animals, studied for the longer period, developed intense proteinuria, decreased creatinine clearance, glomerular necrosis and sclerosis, severe tubulointerstitial nephritis, increased hydroxyproline concentration and tubulointerstitial area. No difference was observed between the nephrotic animals treated with cyclosporine and those not treated. In conclusion, Cyclosporine A reduced proteinuria, glomerular hypertrophy and kidney weight in rats with short-term nephropathy but had no effect on the established nephropathy.

Effect of allopurinol in the course of adriamycin induced nephropathy

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, and 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 ± 6.39 mg/24 h; NCG = 59.8 ± 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 ± 17.5 mg/24h; TNG-I = 49.1 ± 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 ± 22.23 mg/24 h ad 72.66 ± 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48% and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.