Panniculitis in childhood and adolescence

Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs.     

Intestinal parasitic infection: prevalence,knowledge, attitude,and practices among schoolchildren in an urban area of Taiz city,Yemen

BackgroundIntestinal parasitic infections (IPIs) are regarded as one of the main public health problems and socio-economic issues adversely affecting the health of millions of people worldwide. Our study aimed to describe the knowledge, attitude, and practices of local urban schoolchildren in Taiz City towards intestinal parasitic infections.Methods and materialThis is a cross-sectional study conducted in Taiz, Yemen from March to May 2019. A total of 385 schoolchildren were selected using a random sampling technique from 7 primary schools. Wet-mount microscopic examination, formol-ether concentration techniques, and Lugols'' iodine were employed in parasite detection and cyst identification.ResultsOf the 385 schoolchildren examined for IPIs, 107 (27.8%) were positive for the presence of enteric parasites, some having multiple infections. The prevalence was slightly higher in males 46 (28.6%) than in females 61 (27.2%) but have no statistical difference (P = 0.77). Entamoeba histolytica/dispar was the most common infection with 16.4% of cases. A substantial percentage (40.5%) of the respondents displayed poor knowledge. The respondents also revealed inappropriate attitudes and practices that contribute to the prevalence of IPIs in the study.ConclusionsThe study revealed the prevalence of intestinal parasites among the schoolchildren in Taiz, Yemen, suggesting that IPIs remain a major public health problem. Entamoeba histolytica/dispar was the most prevalent intestinal parasites identified among the schoolchildren. Age, poor knowledge of the mode of transmission, prevention, and acquisition of IPIs, and poor habitual hygiene practices increase the risk of acquiring intestinal infections.     

Prediction of successful dose reduction or discontinuation of adalimumab,etanercept, or infliximab in rheumatoid arthritis patients using serum drug levels and antidrug antibody measurement

Background: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug antibodies (ADAb) can predict successful dose reduction (in patients with high DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid arthritis (RA) patients.

Research design and methods: RA patients that were using adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing well, were tapered until discontinuation or flare (1–1.5 year follow up). Random timed DL for adalimumab and etanercept and trough DL for infliximab were measured before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut-off DL were determined.

Results: No predictive value of adalimumab and infliximab DL for all outcomes were found, except for an inverse association of lower etanercept DL and higher chance for successful dose reduction (Area Under the Curve (AUC) 0.36, 95% CI 0.23–0.49; cut-off <2.6 mg/l). In sub analyses, higher adalimumab trough DL predicted successful dose reduction (AUC 0.86, 0.58–1.00; cut-off >7.8). ADAb were infrequent and not predictive of successful discontinuation.

Conclusions: No predictive value of baseline adalimumab, etanercept and infliximab DL or ADAb for successful dose reduction or discontinuation in RA was found in this context, with the possible exception of high adalimumab trough levels for successful dose reduction.     

Risk factors for tuberculosis in older children and adolescents: a matched case–control study in Recife,Brazil

Background

Tuberculosis is a major disease worldwide and most research focus on risk factors for adults, although there is a marked adolescent peak in incidence. The objective of this study was to identify risk factors for tuberculosis in children aged 7 to 19.

Methods

A case control study matched by age with 169 cases and 477 controls. The study population consisted of adolescents and older children from Recife, Brazil. Cases were individuals diagnosed with tuberculosis in the control programme and controls were selected in the neighborhood of cases. Conditional logistic regression was used to identify risk factors.

Results

Cigarette smoking increased by 50% the risk of tuberculosis but that this was not statistically significant (OR?=?1.6). Other risk factors were sleeping in the same house as a case of tuberculosis (OR?=?31.6), living in a house with no piped water (OR?=?7.7) (probably as a proxy for bad living conditions), illiteracy (OR?=?3.7) and male sex (OR?=?1.8). The increase in risk with living in houses with no piped water was much more marked in males. The proportion of cases of tuberculosis attributed to contact with someone with TB was 38% and to illiteracy, lack of piped water and smoking, 20%.

Conclusion

Household contact with tuberculosis, social factors and male sex play the biggest role in determining risk of TB disease among children and adolescents in the study. We recommend further research on the relationship of cigarette smoking on tuberculosis in adolescents, and on whether the sex differentials are more marked in bad living conditions. Separate studies should be conducted in older children and in adolescents.

     

4α-phorbol 12,13-didecanoate activates cultured mouse dorsal root ganglia neurons independently of TRPV4

Background and Purpose

The Ca²⁺-permeable cation channel TRPV4 is activated by mechanical disturbance of the cell membrane and is implicated in mechanical hyperalgesia. Nerve growth factor (NGF) is increased during inflammation and causes mechanical hyperalgesia. 4α-phorbol 12,13-didecanoate (4αPDD) has been described as a selective TRPV4 agonist. We investigated NGF-induced hyperalgesia in TRPV4 wild-type (+/+) and knockout (–/–) mice, and the increases in [Ca²⁺]_i produced by 4αPDD in cultured mouse dorsal root ganglia neurons following exposure to NGF.

Experimental Approach

Withdrawal thresholds to heat, von Frey hairs and pressure were measured in mice before and after systemic administration of NGF. Changes in intracellular Ca²⁺ concentration were measured by ratiometric imaging with Fura-2 in cultured DRG and trigeminal ganglia (TG) neurons during perfusion of TRPV4 agonists.

Key Results

Administration of NGF caused a significant sensitization to heat and von Frey stimuli in TRPV4 +/+ and –/– mice, but only TRPV4 +/+ mice showed sensitization to noxious pressure. 4αPDD stimulated a dose-dependent increase in [Ca²⁺]_i in neurons from +/+ and –/– mice, with the proportion of responding neurons and magnitude of increase unaffected by the genotype. In contrast, the selective TRPV4 agonist GSK1016790A failed to stimulate an increase in intracellular Ca²⁺ in cultured neurons. Responses to 4αPDD were unaffected by pretreatment with NGF.

Conclusions and Implications

TRPV4 contributes to mechanosensation in vivo, but there is little evidence for functional TRPV4 in cultured DRG and TG neurons. We conclude that 4αPDD activates these neurons independently of TRPV4, so it is not appropriate to refer to 4αPDD as a selective TRPV4 agonist.     

破坏泛素依赖的蛋白水解通路对p53转录激活的抑制作用

目的 :研究功能性泛素化及蛋白酶体水解过程对p5 3转录激活的影响。方法 :通过瞬时转染报告基因法 ,测定内源、外源性p5 3或p5 3转录活性片断的转录能力 (荧光素酶活性 ) ;Western blot法测定细胞内p5 3及其靶蛋白p2 1waf1 的表达水平。结果 :抑制蛋白酶体水解过程 ,细胞内源、外源性p5 3及p5 3转录活性片断的转录能力均降低 ;泛素化途径缺失时 ,p5 3转录能力被显著抑制 ,虽然细胞内p5 3蛋白堆积 ,但其下游靶蛋白p2 1waf1 的表达却无增加。结论 :p5 3泛素蛋白酶体水解途径与其转录激活过程存在功能性联系