Review of standard paediatric neuroradiology MRI protocols from 12 UK tertiary paediatric hospitals: is there much variation between centres?

AIM: To investigate how magnetic resonance imaging (MRI) examinations are protocolled in tertiary paediatric neuroradiology centres around the UK for some of the more common presentations encountered in paediatric neuroradiology, and to identify any variations of note. MATERIALS AND METHODS: All 19 UK tertiary paediatric neuroradiology centres registered with the British Society of Neuroradiologists-Paediatric Group were contacted and asked if they could provide a copy of their standard MRI protocols. Twelve responded (63%) and 10 of the more common presentations were selected and the standard acquired sequences obtained at each participating centre were compared. Where available the collated protocols were also compared against current published guidance. RESULTS: The basic sequences carried out by centres around the UK are similar; however, there are lots of variations overall. The only standardised protocol currently being implemented nationally in paediatric imaging is that for brain tumours. Otherwise, chosen protocols are generally dependent on the preferences and technical capabilities of individual centres. Suggested published protocols also exist for non-accidental injury (NAI), multiple sclerosis, epilepsy, and head and neck imaging. CONCLUSIONS: The differences in MRI protocolling depend in part on technical capabilities and in part on the experience and preferences of the paediatric neuroradiologists at each centre. For most presentations, there is no consensus as to what constitutes the perfect protocol. The present results will be useful for specialist centres who may wish to review their current protocols, and for more generalist centres to use as a reference to guide their MRI protocolling.

Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

Safety, Precautions, and Modalities in Cancer Rehabilitation: an Updated Review.

PURPOSE OF REVIEW: Providing rehabilitation to patients with cancer can be challenging due to the medical complexity associated with the illness and its treatments. This article provides the reader with a summary of frequently encountered medical conditions in the cancer population and associated safety considerations and precautions. An update on treatment modalities commonly used for symptom management is also presented. RECENT FINDINGS: Cancer and cancer treatments can cause changes in multiple organ systems. Special considerations and precautions are necessary to provide safe and effective rehabilitation. Physical modalities can be used as monotherapy or adjunct to treatment for common cancer-related side effects with recent studies noting benefit with a variety of modalities. SUMMARY: Detailed assessment of the cancer patient is necessary before implementing a rehabilitation program. Understanding cancer and side effects of treatments, including newer options, are necessary to provide safe care.

CD4+ CD25+ FOXP3+ T cell frequency in the peripheral blood is a biomarker that distinguishes intestinal tuberculosis from Crohn's disease.

BACKGROUND: Distinguishing between Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) has been a challenging task for clinicians due to their similar presentation. CD4+FOXP3+ T regulatory cells (Tregs) have been reported to be increased in patients with pulmonary tuberculosis. However, there is no such data available in ITB. The aim of this study was to investigate the differential expression of FOXP3+ T cells in patients with ITB and CD and its utility as a biomarker. METHODS: The study prospectively recruited 124 patients with CD, ITB and controls: ulcerative colitis (UC) and patients with only haemorrhoidal bleed. Frequency of CD4+CD25+FOXP3+ Tregs in peripheral blood (flow cytometry), FOXP3 mRNA expression in blood and colonic mucosa (qPCR) and FOXP3+ T cells in colonic mucosa (immunohistochemistry) were compared between controls, CD and ITB patients. RESULTS: Frequency of CD4+CD25+FOXP3+ Treg cells in peripheral blood was significantly increased in ITB as compared to CD. Similarly, significant increase in FOXP3+ T cells and FOXP3 mRNA expression was observed in colonic mucosa of ITB as compared to CD. ROC curve showed that a value of >32.5% for FOXP3+ cells in peripheral blood could differentiate between CD and ITB with a sensitivity of 75% and a specificity of 90.6%. CONCLUSION: Phenotypic enumeration of peripheral CD4+CD25+FOXP3+ Treg cells can be used as a non-invasive biomarker in clinics with a high diagnostic accuracy to differentiate between ITB and CD in regions where TB is endemic.

T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load.

Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo-endothelial system caused by protozoan parasites Leishmania donovani and L. infantum, which are known to induce host T cell suppression. To understand the impact of parasite load on T cell function, the present was focused on parasite load with T cell function in bone marrow of 26 VL patients. We observed significant enrichment of forkhead box protein 3 (FoxP3)+ (P = 0·0003) and interleukin (IL)-10+ FoxP3+ regulatory T cells (Treg ) (P = 0·004) in the bone marrow (BM) of patients with high parasite load (HPL) compared with low parasite load (LPL). Concordantly, T effector cells producing interferon (IFN)-γ (P = 0·005) and IL-17A (P = 0·002) were reduced in the BM of HPL. Blocking of Treg -cell derived suppressive cytokines [(IL-10 and transforming growth factor (TGF)-ß] rescued the effector T cells and their functions. However, it was observed that TGF-ß levels were dominant, favouring Treg cell differentiation. Furthermore, the low ratio of IL-6/TGF-ß favours the suppressive milieu in HPL patients. Here we show the change in levels of various cytokines with the parasitic load during active VL, which could be helpful in devising newer immunotherapeutic strategies against this disease.

Exonal switch down-regulates the expression of CD5 on blasts of acute T cell leukaemia.

To date, CD5 expression and its role in acute T cell lymphoblastic leukaemia (T-ALL) have not been studied closely. We observed a significant reduction in surface expression of CD5 (sCD5) on leukaemic T cells compared to autologous non-leukaemic T cells. In this study, we have shown the molecular mechanism regulating the expression and function of CD5 on leukaemic T cells. A total of 250 patients suffering from leukaemia and lymphoma were immunophenotyped. Final diagnosis was based on their clinical presentation, morphological data and flow cytometry-based immunophenotyping. Thirty-nine patients were found to be of ALL-T origin. Amplification of early region of E1A and E1B transcripts of CD5 was correlated with the levels of surface and intracellular expression of CD5 protein. Functional studies were performed to show the effect of CD5 blocking on interleukin IL-2 production and survival of leukaemic and non-leukaemic cells. Lack of expression of sCD5 on T-ALL blasts was correlated closely with predominant transcription of exon E1B and significant loss of exon E1A of the CD5 gene, which is associated with surface expression of CD5 on lymphocytes. High expression of E1B also correlates with increased expression of cytoplasmic CD5 (cCD5) among leukaemic T cells. Interestingly, we observed a significant increase in the production of IL-2 by non-leukaemic T cells upon CD5 blocking, leading possibly to their increased survival at 48 h. Our study provides understanding of the regulation of CD5 expression on leukaemic T cells, and may help in understanding the molecular mechanism of CD5 down-regulation.

Unsupervised Learning in PET Radiomics.

In this study, we investigated large scale radoimics on 116 breast cancer patients. We are particularly interested in unsupervised learning to bicluster patients and features in order to associate such biclusters with the disease characteristics. The results show that radiomics features with wavelet features have a better biclustering ability. And 172 radiomics features have shown a better classification capability.

Programmed death-1+ T cells inhibit effector T cells at the pathological site of miliary tuberculosis.

Optimal T cell activation is vital for the successful resolution of microbial infections. Programmed death-1 (PD-1) is a key immune check-point receptor expressed by activated T cells. Aberrant/excessive inhibition mediated by PD-1 may impair host immunity to Mycobacterium tuberculosis infection, leading to disseminated disease such as miliary tuberculosis (MTB). PD-1 mediated inhibition of T cells in pulmonary tuberculosis and TB pleurisy is reported. However, their role in MTB, particularly at the pathological site, remains to be addressed. The objective of this study was to investigate the role of PD-1-PD-ligand 1 (PD-L1) in T cell responses at the pathological site from patients of TB pleurisy and MTB as clinical models of contained and disseminated forms of tuberculosis, respectively. We examined the expression and function of PD-1 and its ligands (PD-L1-PD-L2) on host immune cells among tuberculosis patients. Bronchoalveolar lavage-derived CD3 T cells in MTB expressed PD-1 (54·2 ± 27·4%, P ≥ 0·0009) with significantly higher PD-1 ligand-positive T cells (PD-L1: 19·8 ± 11·8%; P ≥ 0·019, PD-L2: 12·6 ± 6·2%; P ≥ 0·023), CD19+ B cells (PD-L1: 14·4 ± 10·4%; P ≥ 0·042, PD-L2: 2·6 ± 1·43%; not significant) and CD14+ monocytes (PD-L1: 40·2 ± 20·1%; P ≥ 0·047, PD-L2: 22·4 ± 15·6%; P ≥ 0·032) compared with peripheral blood (PB) of MTB and healthy controls. The expression of PD-1 was associated with a diminished number of cells producing effector cytokines interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-2 and elevated apoptosis. Locally accumulated T cells were predominantly PD-1+ -PD-L1+ , and blocking this pathway restores the protective T cell response. We conclude that M. tuberculosis exploits the PD-1 pathway to evade the host immune response by altering the T helper type 1 (Th1) and Th2 balance at the pathological site of MTB, thereby favouring disease dissemination.

Status Report ­ The Cancer in Young People in Canada surveillance system.

TITRE: Rapport d'étape - Le système de surveillance Cancer chez les jeunes au Canada. INTRODUCTION: Même si le cancer infantile demeure la principale cause de décès lié à la maladie chez les enfants de moins de 14 ans, il est relativement rare. Chaque année au Canada, environ 910 enfants reçoivent un diagnostic de cancer et 139 meurent de la maladie. Sur le plan biologique, les cancers infantiles diffèrent de ceux habituellement observés chez les adultes. Chez ces derniers, la majorité des cancers sont des carcinomes du tissu épithélial qui tapisse les organes comme le sein, le poumon, le colon et la prostate. Chez les enfants, les carcinomes sont rares, et les tumeurs pédiatriques sont le plus souvent d'origine embryonnaire ou hématopoïétique. Les groupes de diagnostic les plus nombreux sont ceux de la leucémie, du lymphome et des cancers du système nerveux central. Comparativement aux cancers chez les adultes, les cancers chez les enfants ont des périodes de latence plus courtes et sont généralement plus agressifs, envahissants et avancés au moment du diagnostic. Malgré le rang élevé qu'occupe le cancer comme cause de décès chez les enfants, le taux de survie s'est grandement amélioré au cours des vingt dernières années, de sorte que les enfants survivent au cancer plus que jamais auparavant. Toutefois, plus de 60 % des survivants d'un cancer infantile sont confrontés aux effets secondaires physiques et psychologiques à long terme de la maladie et de son traitement, et presque 30 % d'entre eux éprouvent des effets tardifs graves ou potentiellement mortels. Les survivants d'un cancer infantile présentent un risque 11 fois plus élevé de décès, un risque accru de développer un second cancer jusqu'à 30 ans après le traitement ainsi qu'un large éventail de problèmes chroniques d'ordres physique, psychosocial et cognitif. La prise en compte de la nature particulière des cancers dans ce groupe d'âge et des effets tardifs à long terme d'ampleur considérable ont incité de nombreux pays à mettre sur pied des systèmes spécialisés de surveillance et de suivi du cancer chez les enfants. En 2009, l'Agence de la santé publique du Canada (ASPC) a lancé à l'échelle du pays un système spécialisé de surveillance du cancer chez les enfants qui assure un suivi actif des enfants de 14 ans et moins ayant été traités dans l'un des 17 centres d'oncologie pédiatrique du Canada. En fait, le programme Cancer chez les jeunes au Canada (CCJC) est le renouvellement du Programme canadien de surveillance et de lutte contre le cancer chez les enfants (PCSLCE) du gouvernement fédéral. Créé en 1992 dans le cadre de l'initiative Grandir ensemble, ce programme recueille des données exhaustives sur le diagnostic de cancer chez les enfants, les traitements, l'issue de la maladie et l'utilisation des services de santé. Dans cet article, nous décrivons les forces et les réussites de CCJC en mettant en lumière la rigueur appliquée dans les méthodes de collecte et de contrôle de la qualité des données, ses dernières réalisations et ses orientations futures.

Loss of Runx2 in committed osteoblasts impairs postnatal skeletogenesis.

The Runx2 transcription factor is critical for commitment to the osteoblast lineage. However, its role in committed osteoblasts and its functions during postnatal skeletogenesis remain unclear. We established a Runx2-floxed line with insertion of loxP sites around exon 8 of the Runx2 gene. The Runx2 protein lacking the region encoded by exon 8 is imported into the nucleus and binds target DNA but exhibits diminished transcriptional activity. We specifically deleted the Runx2 gene in committed osteoblasts using 2.3-kb col1a-Cre transgenic mice. Surprisingly, the homozygous Runx2 mutant mice were born alive. The Runx2 heterozygous and homozygous null were grossly indistinguishable from wild-type littermates at birth. Runx2 deficiency did not alter proliferative capacity of osteoblasts during embryonic development (E18). Chondrocyte differentiation and cartilage growth in mutants was similar to wild-type mice from birth to 3 months of age. Analysis of the embryonic skeleton revealed poor calcification in homozygous mutants, which was more evident in bones formed by intramembranous ossification. Runx2 mutants showed progressive retardation in postnatal growth and exhibited significantly low bone mass by 1 month of age. Decreased bone formation was associated with decreased gene expression of osteoblast markers and impaired collagen assembly in the extracellular matrix. Consequently, Runx2 mutant bones exhibited decreased stiffness and structural integrity. By 3 months of age, bone acquisition in mutant mice was roughly half that of wild-type littermates. In addition to impaired osteoblast function, mutant mice showed markedly decreased osteoclast number and postnatal bone resorption. Taken together, functional deficiency of Runx2 in osteoblasts does not result in failed embryonic skeletogenesis but disrupts postnatal bone formation.

MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes.

Recent advances in cancer biology have emerged important roles for microRNAs (miRNAs) in regulating tumor responses. However, their function in mediating intercellular communication within the tumor microenvironment is thus far poorly explored. Here, we found miR-206 to be abrogated in human pancreatic ductal adenocarcinoma (PDAC) specimens and cell lines. We show that miR-206 directly targets the oncogenes KRAS and annexin a2 (ANXA2), thereby acting as tumor suppressor in PDAC cells by blocking cell cycle progression, cell proliferation, migration and invasion. Importantly, we identified miR-206 as a negative regulator of oncogenic KRAS-induced nuclear factor-κB transcriptional activity, resulting in a concomitant reduction of the expression and secretion of pro-angiogenic and pro-inflammatory factors including the cytokine interleukin-8, the chemokines (C-X-C motif) ligand 1 and (C-C motif) ligand 2, and the granulocyte macrophage colony-stimulating factor. We further show that miR-206 abrogates the expression and secretion of the potent pro-lymphangiogenic factor vascular endothelial growth factor C in pancreatic cancer cells through an NF-κB-independent mechanism. By using in vitro and in vivo approaches, we reveal that re-expression of miR-206 in PDAC cells is sufficient to inhibit tumor blood and lymphatic vessel formation, thus leading to a significant delay of tumor growth and progression. Taken together, our study sheds light onto the role of miR-206 as a pleiotropic modulator of different hallmarks of cancer, and as such raising the intriguing possibility that miR-206 may be an attractive candidate for miRNA-based anticancer therapies.

Runx2 activity in committed osteoblasts is not essential for embryonic skeletogenesis.

Runx2 transcription factor is essential for the development of mineralized tissue, and is required for osteoblast commitment and chondrocyte maturation. Mice with global deletion of Runx2 exhibit complete failure of bone tissue formation, while chondrocyte-specific Runx2-deficient mice lack endochondral ossification. However, the function of Runx2 after commitment of mesenchymal cells to the osteoblast lineage remains unknown. Here, we elucidate the osteoblast-specific requirements of Runx2 during development of the tissue. Runx2 was deleted in committed osteoblasts using Cre-recombinase driven by the 2.3kbCol1a1 promoter. Surprisingly, Runx2(ΔE8/ΔE8) mice were born alive and were essentially indistinguishable from wild-type littermates. At birth, we failed to detect any alterations in skeletal patterning or extent of bone development in homozygous mutants. However, by 4 weeks of age, mutant mice showed obvious growth deficiencies, and weighed 20-25% less than sex-matched wild-type littermates. Micro-CT analysis of the hindlimb revealed a dramatic decrease of 50% in both cortical and trabecular bone volume compared with wild-type mice. Consistent with this observation, trabecular number and thickness were decreased by 51% and 21%, respectively, and trabecular space was increased by 2-fold in limbs of Runx2(ΔE8/ΔE8) mice. In addition to poor acquisition of bone mass, the average density of hydroxyapatite was markedly decreased in bone of Runx2(ΔE8/ΔE8) mice. Together, these findings demonstrate that loss of Runx2 activity in committed osteoblasts impairs osteoblast function, and that Runx2 is critical for postnatal, but not embryonic endochondral ossification.

Runx2 regulates endochondral ossification through control of chondrocyte proliferation and differentiation.

Synthesis of cartilage by chondrocytes is an obligatory step for endochondral ossification. Global deletion of the Runx2 gene results in complete failure of the ossification process, but the underlying cellular and molecular mechanisms are not fully known. Here, we elucidated Runx2 regulatory control distinctive to chondrocyte and cartilage tissue by generating Runx2 exon 8 floxed mice. Deletion of Runx2 gene in chondrocytes caused failure of endochondral ossification and lethality at birth. The limbs of Runx2(ΔE8/ΔE8) mice were devoid of mature chondrocytes, vasculature, and marrow. We demonstrate that the C-terminus of Runx2 drives its biological activity. Importantly, nuclear import and DNA binding functions of Runx2 are insufficient for chondrogenesis. Molecular studies revealed that despite normal levels of Sox9 and PTHrP, chondrocyte differentiation and cartilage growth are disrupted in Runx2(ΔE8/ΔE8) mice. Loss of Runx2 in chondrocytes also impaired osteoprotegerin-receptor activator of NF-κB ligand (OPG-RANKL) signaling and chondroclast development. Dwarfism observed in Runx2 mutants was associated with the near absence of proliferative zone in the growth plates. Finally, we show Runx2 directly regulates a unique set of cell cycle genes, Gpr132, Sfn, c-Myb, and Cyclin A1, to control proliferative capacity of chondrocyte. Thus, Runx2 is obligatory for both proliferation and differentiation of chondrocytes.

Studies on production of fructo-oligosaccharides (FOS) by gamma radiation processing of microbial levan.

Microbial levan, a natural polymer of fructose, was produced and purified by alcohol precipitation from culture supernatants of Bacillus megaterium type 1 grown in an optimized liquid sucrose medium. GPC analysis showed that the yield of the major fraction of levan having molecular weight ~5000 D increased with increase in sucrose concentration in the broth. Levan subjected to (60)Co-gamma radiation as well as acid hydrolysis was investigated by rheometry, UV-visible spectrophotometry and gel permeation chromatography (GPC) techniques. Unlike most of the polysaccharides, levan powder exhibited good radiation degradation stability up to 150 kGy. Gamma irradiation of 10% levan aqueous solution at 250 kGy yielded 63.0% fructo-oligosaccharide (FOS) with an average molecular weight of 1250 D. Acid hydrolysis of levan using 0.5 N HCl for 60 min treatment time gave rise to the desired FOS with lower yield (23.1%) as compared to that obtained in gamma radiolysis process.

Synchronous x-ray and radio mode switches: a rapid global transformation of the pulsar magnetosphere.

Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.

Langerhans cell histiocytosis: a multisystem disorder.

Langerhans cell histiocytosis can involve single or multiple organ/tissue systems and may go undiagnosed for years until it enters the clinician's differential diagnosis framework. We report on a young patient who initially presented with diabetes insipidus and subsequently with pyrexia of unknown origin. She progressed from single system Langerhans cell histiocytosis to multisystem involvement and remains in long-term remission following chemotherapy.

Trends in incidence of childhood cancer in Canada, 1992-2006.

INTRODUCTION: Cancer is the leading cause of disease-related death in children aged 1 to 14 years in Canada. Despite the importance to public health of childhood cancer, there have been few reports on Canadian trends published in the peer-reviewed literature. This study examines childhood cancer trends by age, sex, and province of residence using the most current cancer registration data. METHODS: Data from the population-based Canadian Cancer Registry were used to compute incidence trends in primary cancers diagnosed between 1992 and 2006 in children (0-14 years) for the 12 major diagnostic groups of the International Classification of Childhood Cancer, 3rd Edition. RESULTS: Between 1992 and 2006, incidence rates for all cancers remained stable, although trends varied by cancer type. We observed a significant decrease in retinoblastoma in boys for the entire period (-6.5% per year) and an increase in leukemia from 1992 to 1999 (+3.5% per year). In girls, there was a significant decrease in renal tumours from 1998 to 2006 (-5.7% per year) and an increase in hepatic tumours from 1997 to 2006 (+8.1% per year). Differences by age and province were also apparent. Some caution should be exercised when interpreting trends involving a small number of cases per year and those with wide 95% confidence intervals. CONCLUSIONS: Our findings suggest an ongoing need for population-based surveillance and etiologic research.

Study of clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo undergoing melanocyte transplantation.

BACKGROUND: Stability is considered the most important parameter before performing any melanocyte transplantation procedure in vitiligo; however, current criteria rely on the history given by the patients. OBJECTIVE: This study was undertaken to determine the clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo to facilitate better patient selection for melanocyte transplantation and to understand immunological mechanisms for disease activity. METHODS: Thirty-three patients with generalized vitiligo with < 10% body surface area involved were allocated to three clinical stability groups: Group 1 (stability > 3 months but < 1 year), Group 2 (≥ 1 year but < 2 years) and Group 3 (≥ 2 years). Melanocyte transplantation was done using suction blister epidermal grafting (SBEG) on a single patch. Blood was drawn for catalase estimation from all patients and from 10 healthy control subjects. A 3-mm punch biopsy was taken on the day of transplantation from the margin of the macule in the first five patients in each group for the immunohistochemistry of CD4, CD8, CD45RO, CD45RA and FoxP3. Those with ≥ 75% repigmentation at 6 months were labelled as responders. RESULTS: The success rate was 0% in Group 1, 37·5% in Group 2 and 77·8% in Group 3. The difference in the success rate between the groups was statistically significant (P = 0·005). The median period of stability was significantly higher in the responders compared with that in the nonresponders (P = 0·001). Catalase levels were not significantly different between patients in the three groups of cases and in controls, or between responders and nonresponders. Lesional CD8 cells were significantly higher in Group 1 compared with Group 3. The percentages of CD8 and CD45RO cells were significantly higher in the nonresponders compared with the responders. CONCLUSION: Along with clinical stability, the proportion of CD8 and CD45RO cells in skin biopsies might help to determine the stability of the disease and thereby predict the success of transplantation.

Frequency of T cell expressing Th1 and Th2 associated chemokine receptor in patients with renal allograft dysfunction.

Acute rejection of human renal allografts is a frequent, serious posttransplantation complication, occurring in up to 50% of recipients. Leukocyte recruitment is a central feature of acute allograft rejection. Chemokine receptors are expressed on leukocytes in a cell type-specific manner. Recently CCR5+ and CXCR3+ cells have been observed in allograft biopsy specimens of patients undergoing acute cellular rejection (ACR). Herein we investigated the expression of Th1 (CCR5, CXCR3, and CCR2) and Th2 (CCR4, CCR3, and CCR8)-associated chemokine receptors on CD4 and CD8 T-cell populations. We sought to correlate chemokine receptor expression in peripheral blood T-cell subsets with the types of graft dysfunction (biopsy-proven rejections). In the peripheral blood CD4+ and CD8+ T-cell populations of patients with graft dysfunction, we observed a high frequency of Th1-associated chemokine receptors CCR5+ and CCR2+ but not CXCR3.