Acute Idiopathic Thrombocytopenic Purpura Research Articles

Hypermethylation of the FOXP3 gene regulates Tregs immunodysregulation in chronic idiopathic thrombocytopenic purpura.

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a breakdown of immune tolerance; in ITP, the body's immune system mistakenly attacks and destroys platelets. This study aims to investigate the role and underlying mechanisms of FOXP3 in chronic ITP. Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in CD4+CD25+ T lymphocytes from 20 patients with chronic ITP (CITP), 20 acute ITP (AITP) controls, and 20 healthy individuals.CD4+CD25+ Treg cells were isolated from peripheral blood of patients with CITP using magnetic beads and then treated with phosphate-buffered saline solution or decitabine (a methylation inhibitor) for 48 h. The levels of interleukin-2 (IL-2), IL-10, and transforming growth factor-beta1 (TGF-β1) in the plasma and CD4+CD25+ Treg cells were assessed by Enzyme-linked-immunosorbent serologic assay and quantitative real-time polymerase chain reaction (qRT-PCR). FOXP3 level was measured by qRT-PCR and Western blot analysis. Methylation-specific PCR (MS-PCR) was adopted to detect the status of FOXP3 methylation. The number of Treg cells and the contents of IL-2, IL-10, and TGF-β1 decreased in patients with CITP, compared to the AITP control group and normal group. FOXP3 expression was reduced and FOXP3 methylation increased in patients with CITP, compared to the AITP control group and normal group. Hypermethylation of FOXP3 promoter led to decrease in FOXP3 level in Treg cells. Inhibition of FOXP3 promoter hypermethylation promoted the secretion of IL-2, IL-10, and TGF-β1 in Treg cells. The number of Treg cells in CITP patients decreased, and the hypermethylation of FOXP3 promoter led to reduction of its expression in Treg cells, thus affecting the immune functioning of Treg cells.

Unilateral Sensorineural Hearing Loss in Children Associated With Sjögren's Syndrome

The occurrence of unilateral sensorineural hearing loss (SNHL) during school age is relatively rare and accounts for approximately 6% of all deafness in childhood. We present two cases involving children who were diagnosed with SNHL associated with Sjögren's syndrome (SS). Case 1: An eight-year-old girl with an approximately two-year clinical history of gradual hearing loss was diagnosed with SNHL associated with SS based on histological findings of inflammation in the salivary glands and the presence of serum anti-Sjögren's syndrome-A antibody. Case 2: An eight-year-old boy with acute idiopathic thrombocytopenic purpura in whom unilateral hearing loss, which was not associated with any problems in daily life, was detected during hospitalization and who was finally diagnosed with SNHL and SS. Steroid treatment was ineffective for both patients. The previously unrecognized combination of SNHL with SS should be considered in the diagnosis of unilateral SNHL, even in children.

Thiol / disulfide balance and oxidative stress parameters in pediatric patients diagnosed with acute and chronic idiopathic thrombocytopenic purpura.

Changes in oxidative stress and thiol / disulfide balance are thought to play a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Our study investigates total oxidant level (TOS), total antioxidant level (TAS), oxidative stress index (OSI) levels and thiol / disulfide balance in pediatric patients with acute and chronic ITP. Thirty four patients with acute ITP, eighteen patients with chronic ITP and thirty three healthy children (control) were included. TOS, TAS, OSI, thiol / disulfide balance were analyzed. In acute ITP, TAS levels were lower than chronic ITP and control, TOS and OSI levels were higher than control, and native thiol level was lower than chronic ITP (p < 0.05). In acute ITP; disulfide level, disulfide / native thiol and disulfide / total thiol ratios were higher than chronic ITP and control, and native thiol / total thiol ratio was lower than chronic ITP and control group (p = 0.038, p = 0.018, respectively). TOS and OSI levels of the chronic ITP were higher than the control group (p < 0.05). The results of this study have shown that oxidative stress increases in children with acute ITP and chronic ITP, that thiol / disulfide balance is disrupted in favor of disulfide in acute ITP, and that thiol / disulfide balance isn`t disrupted in chronic ITP patients whose platelet count is close to normal and who don`t require treatment.

Helicobacter pylori Eradication in Adult Patients with Acute Idiopathic Thrombocytopenic Purpura (ITP)

Helicobacter pylori Eradication in Adult Patients with Acute Idiopathic Thrombocytopenic Purpura (ITP)

Regulatory T cell CD4 ‏&CD25‏ expression and chemokine C-X-C ligand 13 level before and after corticosteroid therapy in pediatric ITP patients

Childhood Idiopathic thrombocytopenic purpura (ITP) is one of the most commons autoimmune bleeding disorders characterized by isolated, immune-mediated low platelet count, the T-follicular helper (Tfh) cells are a subset of effector CD4 (+) T cells, that plays a pivotal role in maintaining self-tolerance, deregulation of Tfh activities has a key role in immune process taking place in ITP in which the production of platelet autoantibodies might be caused by cytokine network dysregulation. The objective of our study was to analyze the relationship of Tfh cells CD4&CD25 and C-X-C ligand 13 (CXCL13) expressions before and after steroid thereby in pediatric ITP. Material and method: the study included 45 pediatric patients with acute ITP and 20 healthy controls; we used flowcytometry to assess percentages of CD4‏ and CD25‏ cells as markers of regulatory T cells, also, the serum level of interleukin- CXCL13 was measured by ELISA at diagnosis and after 4 weeks receiving corticosteroid. Results: the expression of CD4‏ & CD25‏ ‏ markers were significantly reduced in ITP cases, who also showed an elevated CXCL13 level in comparison to controls, however, the level of CXCL13 declined after treatment, the CXCL13 optimum cut off point for predicting ITP response to therapy was determined to be 90 pg/ml with AUC 0.976, Sensitivity 88.89% and Specificity 100% P-value < 0.00. Conclusion: Serum CXCL-13 levels could be used as a significant predictor of response to therapy in ITP patients, CD4&‏CD25 expression has a role in the pathogenesis of childhood acute ITP principally linked to the level of platelet count drop.

Trombocitopenia inmune primaria aguda presentación clínica y manejo en pacientes pediátricos, Hospital Mario Catarino Rivas

Antecedentes: La trombocitopenia inmune primaria, conocida como púrpura trombocitopénica idiopática (PTI), es un trastorno autoinmune adquirido que afecta adultos y niños. Objetivo: Caracterizar los pacientes pediátricos con PTI aguda mediante su identificación y seguimiento en el Hospital Nacional Mario Catarino Rivas (HNMCR) entre 1 febrero del 2016 al 31 enero del 2017. Pacientes y Métodos: Estudio cuantitativo, diseño no experimental longitudinal – prospectivo, alcance descriptivo. La población es todo paciente menor de 18 años de edad, que acudió al HNMCR con PTI aguda. La muestra 47 pacientes. Excluidos pacientes previamente diagnosticados con PTI, con segundos episodios o recaídas, con patologías sobre agregadas. Información recopilada mediante un instrumento tipo encuesta: situación demográfica, área geográfica y revisión del expediente clínico, los datos fueron analizados con el programa EPIINFO y EXCEL. Resultados: En cuanto al grupo etario el 56% fueron menores de cinco años de edad, la distribución por sexos hubo predominio del sexo masculino. 81% de los niños fueron hospitalizados, el resto recibió manejo ambulatorio; sin embargo en el 100% se inició alguna terapia con resolución de la trombocitopenia a los 3 meses. Luego del seguimiento, el diagnóstico final de los casos captados fue PTI aguda 58%(n=27), evolucionaron a la cronicidad 20% (n=9), el 22% (n=10) abandonaron seguimiento. Conclusiones: La mayoría de los pacientes con PTI son admitidos al hospital, aunque su conteo de plaquetas no los ponga en riesgo claro de hemorragias espontáneas, por no haber guías de manejo en nuestro hospital.&#x0D; Palabras clavePurpura, Immune, Trombocitopenia

Characteristics of functional somatic syndromes and bodily distress syndrome in the general Danish population–The DanFunD study

Childhood Idiopathic thrombocytopenic purpura (ITP) is one of the most commons autoimmune bleeding disorders characterized by isolated, immune-mediated low platelet count, the T-follicular helper (Tfh) cells are a subset of effector CD4 (+) T cells, that plays a pivotal role in maintaining self-tolerance, deregulation of Tfh activities has a key role in immune process taking place in ITP in which the production of platelet autoantibodies might be caused by cytokine network dysregulation. The objective of our study was to analyze the relationship of Tfh cells CD4&CD25 and C-X-C ligand 13 (CXCL13) expressions before and after steroid thereby in pediatric ITP. Material and method: the study included 45 pediatric patients with acute ITP and 20 healthy controls; we used flowcytometry to assess percentages of CD4‏ and CD25‏ cells as markers of regulatory T cells, also, the serum level of interleukin- CXCL13 was measured by ELISA at diagnosis and after 4 weeks receiving corticosteroid. Results: the expression of CD4‏ & CD25‏ ‏ markers were significantly reduced in ITP cases, who also showed an elevated CXCL13 level in comparison to controls, however, the level of CXCL13 declined after treatment, the CXCL13 optimum cut off point for predicting ITP response to therapy was determined to be 90 pg/ml with AUC 0.976, Sensitivity 88.89% and Specificity 100% P-value < 0.00. Conclusion: Serum CXCL-13 levels could be used as a significant predictor of response to therapy in ITP patients, CD4&‏CD25 expression has a role in the pathogenesis of childhood acute ITP principally linked to the level of platelet count drop.

Analysis of Differentially Expressed Genes and the Interaction Network between Acute and Chronic Idiopathic Thrombocytopenic Purpura in Children

Objective To analyze the differentially expressed genes and key proteins in T cells between acute and chronic idiopathic thrombocytopenic purpura (ITP) in children and provide the basis for the prevention and therapies of this disease. Methods Microarray gene chip data from T cells of children with acute or chronic ITP were downloaded from the GEO Database. The gene expression profiles,gene function,and protein interaction network were analyzed by R,QOE,Networkanalyst,GCBI,and GenClip. Results The gene expression profiles between these two groups were significantly different. Among the 54 675 genes analyzed,there were 457 (0.84%) differentially expressed genes between these two groups. In the protein interaction networks among top 20 differentially expressed genes,the core was JUN(down-regulated) and ITCH(up-regulated),which were both related to the tumor necrosis factor signaling pathway;differentially expressed genes were mainly related to the activation and tolerance of T cell. Conclusions The gene expression profiles differ between acute and chronic ITP patients,suggesting that the gene transcription profile plays a regulatory role in the different stages of ITP. JUN and ITCH may play a role in predict the progression of ITP and may exert their biological functions by regulating the tumor necrosis factor signaling pathway.

IDIOPATHIC THROMBOCYTOPENIC PURPURA

Idiopathic thrombocytopenic purpura is an autoimunne disease with low platelet count and bleeding manifestation like purpura, echymosis, petechie, mucosa membrane bleeding. The cause of ITP is platelet coated with specific thrombocyte autoantibody. Idiopathicthrombocytopenic purpura is classified as primary or secondary. The primary ITP is classified as acute and chronic.. Children and adultonset idiopathic thrombocytopenic purpura are different. An Acute ITP can be found in children and chronic onset can be found in adult.The duration of bleeding may help to distinguish acute and chronic idiopathic thrombocytopenic purpura. The diagnosis of idiopathicthrombocytopenic purpura remains one of exclusion after other thrombocytopenic disease are ruled out based on history and needanamnesa, physical examination, thrombocyte count, perifer blood smear examination, bone marrow smear examination. The treatmentis to raise the platelet count into a hemostatically safe range. This article presented a study case of idiopathic thrombocytopenic purpuraon an old woman with DIC which caused her death.

Acute Kidney Injury, Immune Thrombocytopenic Purpura, and the Infection That Binds Them Together: Disseminated Histoplasmosis.

Untreated human immunodeficiency virus (HIV) can be complicated by opportunistic infections, including disseminated histoplasmosis (DH). Although endemic to portions of the United States and usually benign, DH can rarely act as an opportunistic infection in immunocompromised patients presenting with uncommon complications such as acute kidney injury and idiopathic thrombocytopenic purpura. We report a rare presentation of DH presenting with acute kidney injury and immune thrombocytopenic purpura in an immunocompromised patient with HIV.

High dose, short course prednisolone for acute idiopathic thrombocytopenic purpura (ITP) in children

Background: Immune thrombocytopenia (ITP) is a relatively benign and self-limiting condition. Though its dramatic presentation with skin or mucosal bleeds could be worrisome, the incidence of serious bleeding like intracranial hemorrhage (ICH) is relatively low (&lt;1%) occurs at a very low count of &lt;20,000 /mm3. The aim of the study was to compare a high dose, short course prednisolone with conventional Prednisolone therapy in the treatment of acute ITP of childhood.Methods: 20 cases and 18 retrospective controls with acute ITP were enrolled. The study group received 5mg/kg/day of oral prednisolone for four days. All the controls had received 2mg/kg/day of oral prednisolone for 14 days, tapered and stopped over the third week.Results: The study group was found to have significant decrease in clinical bleeding, (p=0.02), and significant increase in platelet count by day 3 of treatment (p=0.03) but no significant difference in platelet counts on day 7 of treatment (p=0.07) when compared with the control group.Conclusions: We conclude that the high dose short course oral prednisolone is significantly better than the conventional regimen in reducing clinically significant bleeding and raising the platelet count to safe levels within first 72 hours of therapy.

Evaluation of treatment modalities of acute idiopathic throm- bocytopenic purpura in Al-zahraa teaching hospital in Al-Najaf

Background: Acute idiopathic thrombocytopenic purpura(I.T.P) is a bleeding disorder in which the immune system for unknown reason produce antibodies against platelets, which are necessary for normal blood clotting resulting in decrease number of circulating platelets, manifested itself by bleeding tendency, easy brusing or extravasation of blood from capillaries in the skin and mucous membrane .Objective: to choose the most appropriate therapy for acute idiopathic thrombocytopenic purpura management .Methods : 65 patients were enrolled in this retrospective study, who were admitted to AL-Zahraa teaching hospital from January 2000 to January 2010 . Relevant information were collected according to preceding data collection sheet that include age, sex, initial hemoglobin and platelets count, treatment given, response to therapy…These patients subdivided into 3 groups according to initial drug used for their management either prednisolone, I.V.immunoglobulin-G, or anti-D. The response was analyzed according to rapid rise of platelets number in the pre-treatment state. chronic cases of I.T.P were excluded from this study .Results: All patients were aged from 2-12 years with peaks of 2-5 years. Sex ratio (female\male) of 1:1.7 .Our study showed that out of 65 patients, 37(57%) of them were assigned as group 1 who received prednisolone as a conventional therapy ,the response was noted in 31( 86.5%) after few days of treatment. Regarding group 2 patients received I.V immunoglobulin-G, the response of platelets rise was noted in 16( 89%) of cases out of 18 patients . While(10) patients in group 3 who received anti-D as main line of treatment to Rh-positive individuals, the response is observed in only 6( 60%) of cases .Conclusion: Regarding various treatment modalities of idiopathic thrombocytopenic purpura ,it has been noted that oral prednisolone is the best, single, readily available, inexpensive drug that can be taken orally and as outpatient .Recommendation:The availability of other treatment options such as I.V-immunoglobulin-G should be adopted in our hospitals in cases of life- threatening illness as it induces more rapid rise in platelets in comparison with other drugs.

Evaluation of prevalence, clinical spectrum and outcome of acute ITP in children in a tertiary care centre in Odisha, India

Background: Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenic purpura is one of the commonest bleeding disorders encountered in children between the ages of 2 to 10 years affecting both sexes. The objectives of the study were to collect the prospectively data including age, gender, bleeding type, platelet count and other laboratory tests, treatments, responses to treatment and outcomes in children with acute ITP from 1month to 14 years of age over a period of two years.Methods: The present study was conducted in the Department of Paediatrics Shrirama Chandra Bhanj, Medical College and Hospital and Sardar Vallabhbhai Patel Post Graduate Institute of Paediatrics, Cuttack during the period October 2011-Septmber 2013.Results: Total 36 cases of hospitalized acute ITP patients were studied out of 29200 cases. Prevalence of acute ITP was found to be 12.3 per 10,000 of all hospitalized children above 1 month. Male children outnumbered female children by Ratio 1.2. Past history of URTI was present in 78% of cases. Petechaie/purpura was the universal presenting features followed by Oral / Gum bleeding in 67% of cases. 8% of patient experienced clinical bleeding requiring blood transfusion and platelet transfusion. Mean duration of Hospital stay was 6.34 days. Maximum number of Patients (69%) had complete recovery and 14% each had persistent and chronic course.Conclusions: ITP is a common pediatrics disease presenting at any age with low morbidity and mortality. Most children with acute ITP recover in weeks to months. A long-term hospital based prospective study is suggested to know any significant risk factor in patient presenting with acute ITP.

Regulatory and Memory B Lymphocytes in Children With Newly Diagnosed Immune Thrombocytopenia.

BackgroundImmune (idiopathic) thrombocytopenic purpura (ITP) is a primary autoimmune disease. It is characterized by a diminished peripheral platelet count (< 100 × 109/L) caused by platelet destruction with an increased risk of mucocutaneous bleeding. The diagnosis of ITP depends on clinical characteristics and the laboratory examinations conducted, as well as the ability to exclude other diseases associated with thrombocytopenia. Antiplatelet autoantibodies are responsible for platelet destruction and probably for inhibition of megakaryopoiesis. B lymphocytes participate in immune responses through production of antibodies, antigen presentation to T cells, and cytokine secretion. The aims of this study were to investigate the levels of Bregs and memory B lymphocytes in newly diagnosed pediatric ITP patients and to correlate their levels with the course of the disease.MethodsThis study was a case-control study. The study included 30 patients with acute ITP. The patients were recruited from Pediatric Clinical Hematology Unit of Children Hospital, Assiut University. In addition, 20 healthy children of comparable age and sex were taken as controls. The institutional review board approved the study and informed consents were obtained.ResultsThere is a significant alteration of B-cell homeostasis in patients with ITP.ConclusionAnalysis of Bregs and memory B cells could serve as prognostic markers and might guide therapy in ITP patients in the future.

Analysis of HPA gene Polymorphisms in Children with Acute or Chronic ITP

To investigate the frequency distribution of human platelet antigen allele HPA-2 and HPA-15 among the pediatric patients with acute or chronic idiopathic thrombocytopenic purpura (ITP) in Chinese Guangxi area, and to explore the potential correlation of ITP with HPA-2 and HPA-15 gene polymorphisms. The clinical and laboratorial data of 46 children diagnosed as acute ITP and 46 children diagnosed as chronic ITP between January 2007 and December 2014 were collected. Genotyping of HPA-2 and HPA-15 in 92 ITP patients and 48 healthy controls was performed by using polymerase chain reaction (PCR) combined with direct sequencing. The allele frequencies of HPA-2 and HPA-15 were significantly different among the acute, chronic and control groups; the allele frequencies were significantly different between the chronic ITP group and the control group (P<0.0167), while the difference was not statistically significant between the acute and chronic ITP groups as well as between the acute ITP and the control group (P>0.0167). The gene polymorphism of HPA-2 and HPA-15 may correlate with the risk of chronic ITP, but may not correlate with acute ITP in children.

DNA methyltransferase 3B gene promotor and interleukin-1 receptor antagonist polymorphisms in Egyptian children with immune thrombocytopenic purpura

Background and objectives Idiopathic thrombocytopenic purpura (ITP) is an autoimmune condition characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. Many gene polymorphisms have been reported to be closely associated with the susceptibility to ITP. Aim of the work The current study aimed to investigate the association between the DNA methyltransferase DNMT3B-46359 C/T promoter and IL-1Ra polymorphism and the risk for acquisition of pediatric ITP in a cohort of Egyptian children. Patients and methods Genotyping of the studied genes using PCR-RFLP assays was conducted on 40 children with ITP and 20 age-matched and sex-matched normal controls. Results Our results revealed that DNMT3B-46359 C/T heterotype was higher in patients than in controls but did not reach statistical significance and conferred 2.2-fold increased risk for ITP (odds ratio=2.2, confidence interval = 1.4–2.6). There was no statistically significant difference between ITP patients and controls as regards allele frequency. Moreover, there was no statistically significant difference in the clinical and laboratory data between ITP patients with wild or mutant genotypes. Moreover, there was no statistically significant difference in the distribution of DNMT3B-46359 . C/T genotypes between acute and chronic ITP patients. Conclusion This genetic polymorphism cannot be considered as a molecular marker for ITP risk among Egyptian children. Moreover, it is not a molecular predictor for chronicity.

Dental considerations on the management of Idiopathic Thrombocytopenic Purpura in children: case report

Idiopathic Thrombocytopenic Purpura (ITP) is a hematological disease characterized by decreased number of blood platelets. Clinically, children with ITP may present petechiae, ecchymoses, haematuria, epistaxis and occasionally hemorrhage. Oral manifestations include spontaneous gingival bleeding, petechiae or hematomas of the mucosa, palate and tongue. It is important for dentists to be aware of ITP in order to properly recognize this condition and offer the adequate treatment to the patient. The aim of this report was, therefore, to relate the case of a 4-year-old patient with acute ITP, to review its main clinical signs in children and describe the management of these patients at the dental office.

特発性血小板減少性紫斑病を急性発症したC型肝硬変症例に対し集学的加療を行うことで生体肝移植を施行し得た1例

特発性血小板減少性紫斑病を急性発症したC型肝硬変症例に対し集学的加療を行うことで生体肝移植を施行し得た1例

Acute immune thrombocytopenic purpura in childhood Presentation and treatment A Hospital based study

Background: Acute idiopathic thrombocytopenic purpura (ITP) is a self – limiting illness, usually occurring after an infectious disease, and it is due to decrease number of circulating platelets manifests as a bleeding tendency, easy bruising (purpura), or extravasations of blood from capillaries into skin and mucous membranes. &#x0D; Objective: To study and analyze the natural history of idiopathic thrombocytopenic purpura and treatment used in children below 15years. &#x0D; Patients and methods: A cross sectional descriptive study was carried on total of 72 patients their ages range between(1-15)years who were admitted to Children Welfare Teaching Hospital / Baghdad from 1st of July 2010 to30th of June 2011. Seventy two cases admitted during that period and diagnosed as acute immune thrombocytopenic purpura but bone marrow aspiration study was done in 57cases and those cases that were studied and were analyzed to all types of clinical presentation &amp; management used. &#x0D; Results: Age group were ranged from (1-15) years with peak in age group of (1-5) years 38(66.7%), male were 29 (50.9%) equal to female 28 (49.1%). Most cases were reported in spring 25(43.9%), with preceding viral illness was encountered in 37 (64.9%) patients. Most cases were presented with skin rash 54(94.7%) except three cases, the epistaxis was the second presentation 21(36.9%), and the least presentations were intracranial hemorrhage &amp; menorrhagia 1(1.8%). Most of the cases were treated with steroid (91.1%). &#x0D; Conclusions: Bone marrow exanimation is recommended in each case of the thrombocytopenia, and if decision of bone marrow exanimation is taken, it is essentially to do it prior to steroid therapy. Oral prednisolone is the readily available, inexpensive drug that can be taken orally in hospital and as outpatient. Methylprednisolone rapidly increases platelet counts so reduces period of hospitalization, but it is not always available and can be used as in patient treatment only.

Chronic immune thrombocytopenia in childhood

Chronic thrombocytopenias are pathological conditions defined as a persistent platelet count below the normal range for more than 6-12 months, clinically characterized by mucocutaneous bleeding. Recently, an International Working Group of expert clinicians has redefined standard terminology and definitions of primary and secondary chronic immune thrombocytopenia (ITP). A document issued on acute childhood idiopathic thrombocytopenic purpura (AIEOP) provides parents and physicians with guidelines for the management of chronic ITP and gives prominence to the periodic re-evaluation of differential diagnosis. The majority of chronic ITP children do not require pharmacological treatments, especially if symptoms are absent or minimal and the treatment decision depends on several factors, in particular clinical conditions rather than platelets count. The recommendations distinguish three therapeutic strategies: emergency or symptomatic treatment, maintenance therapy and treatment aiming at definitive remission. Experimental/off-label treatment of chronic ITP are reported in the literature, such as the use of rituximab. Currently, other drugs (thrombopoiesis stimulating factors, mycophenolate, dapsone, danazol, azathioprine, rFVIIa, cyclophosphamide, vinca alkaloids and cyclosporine) are recommended in special cases or trials.