Traumatic wound of the heart: value of intraoperative colour Doppler flow imaging

A patient who sustained a traumatic ventricular septal defect from a stab wound is presented. Intraoperative echo-Doppler imaging provided an additional diagnosis of avulsion of anterior papillary muscle of the tricuspid valve prior to cardiotomy. It was concluded that intraoperative echo-Doppler imaging proves a useful guide for cardiac surgery following penetrating trauma.     

Cytogenetic analysis of 52 Indian patients with de novo myelodysplastic syndromes—a comparative analysis of results with reports from Asia

Most published data on myelodysplastic syndromes (MDS) are derived from Western countries, which report MDS as a disease of the elderly. However, it was observed that Asian MDS patients were younger than subjects in Western reports. With this in mind, the study was conducted prospectively on 52 Indian patients to define chromosomal abnormalities and to understand ethno-geographical differences, if any, underlying the pathogenesis of MDS among this Asian population. Cytogenetic analysis was performed using GTG banding and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). The incidence of MDS was predominant in the age group of 41–60 years (44.23%), with a median age at diagnosis of 55 years. The disease was more frequent in males (33 patients, 63.46%) than females (19 patients, 36.53%). Of 48 patients successfully karyotyped, 17 had normal karyotype (35.4%) and 31 patients (64.5%) had a chromosomal abnormality. The most frequent chromosome abnormalities were del 5q/–5 in 13 patients (42%), –7/7q– in 10 patients (32.2%), +8 and del 20q– in 6 cases each (19.3%) and i(17)(q10) in 1 patient (3.2%). In addition to these non-random chromosomal abnormalities, some rare abnormalities were also encountered. A higher rate of transformation to acute myeloid leukaemia (AML) was observed in the Chinese population compared to other Asian countries. The incidence of chromosomal abnormalities varied considerably across the different Asian populations. The overall frequency of chromosomal abnormalities in our study was comparable to most Western reports. Further prospective studies are warranted to elucidate precisely the ethnic differences in the pathogenesis of MDS in the Indian population.     

Concurrent outbreak of leptospirosis and dengue in Mumbai, India, 2002

This prospective study was undertaken to investigate the possibility of a concurrent outbreak of leptospirosis and dengue and to describe the clinical illnesses. From 20 June to 14 November 2002, children who presented to our hospital with a suspected diagnosis of leptospirosis or dengue were admitted. In every child with suspected leptospirosis, a screening latex agglutination test was carried out to detect anti-Leptospira antibodies. The diagnosis of leptospirosis was confirmed by a positive enzyme-linked immunosorbent assay (ELISA) test or microagglutination test. The diagnosis of dengue was confirmed by a positive IgM antibody capture ELISA test. Clinical features in the leptospirosis and leptospirosis-negative groups, and dengue and dengue-negative groups were analysed. Of 90 children screened, 15 (16.7 per cent) had leptospirosis. Two children with Weil's disease died and the remaining 13 responded well to intravenous penicillin. Five clinical features were significantly associated with leptospirosis, namely conjunctival suffusion (p=0.007), haemorrhage (p=0.020), abdominal pain (p=0.011), hepatosplenomegaly (p=0.044), and oedema (p=0.007). As the number of these five features concomitantly present increased, the chances of the child having leptospirosis also increased significantly (p<0.0001). Of 90 children screened, 16 (17.8 per cent) had dengue. All responded well to the treatment and went home. Two clinical features were significantly associated with dengue, namely arthralgia (p=0.020) and thrombocytopenia (p=0.001). If both these features were present, the chances of the child having dengue increased significantly (p=0.001). Our study shows that a concurrent outbreak of leptospirosis and dengue had occurred in the slums of Mumbai city.     

Phrenic nerve palsy in severe tetanus

Unilateral or bilateral raised hemidiaphragms were observed on chest X-ray in three patients with severe tetanus. Diaphragmatic movement was absent on ultrasonography and fluoroscopy. Nerve conduction study confirmed phrenic nerve palsy. Bilateral involvement caused delayed weaning from the ventilator, whereas unilateral involvement was asymptomatic. There was complete recovery from phrenic nerve palsy in all patients.     

Cyclophilin a modulates dendritic cell differentiation from myeloblastic cell KG1

Introduction. Cyclophilin A (CypA) is a ubiquitously distributed intracellular protein as well as secreted protein and has recently been reported to be an immunomodulatory molecule. The objective of this study was to determine the effect of CypA on dendritic cell (DC) differentiation, activation, and functional maturation. Methods. KG1 cells (CD34⁺ human myeloblastic cell line) were treated with cytokines (GM-CSF+IL-4) and/or CypA and expression of cell-surface markers was analyzed by FACS analysis. The antigen uptake capacity of different DCs was determined by FITC-dextran uptake assay. Antigen presentation capacity of DCs was determined by allogeneic mixed lymphocyte reaction (MLR) by [³H]thymidine incorporation assay. To check the T cell polarization of KG1-derived DCs, various Th1 and Th2 cytokines secreted by allo-stimulated CD4⁺ and CD8⁺ T cells were determined by Bioplex cytokine assay. Role of p38 MAP kinase in DC functions was also investigated. Results. During the differentiation of KG1 cells to immature DCs, cell-surface expression of CD11b was increased by 30.6% for CypA alone; 55% for CypA plus cytokines; and 44% for cytokines alone. Similarly, CypA alone increased the cell-surface expression of CD11c by 59% as compared to CypA plus cytokines (68%) and cytokines alone (50%). CypA up regulated the antigen uptake capacity of the immature DCs to a greater extent (5 times) as compared to cytokines alone (2.5 times). Moreover, CypA augmented the capacity of DCs to present antigens to allogenic CD8⁺ T cells and also increased the secretion of Th1-type cytokines TNF-α and IFN-γ from the allogenic CD4⁺ T cells. Furthermore, CypA induced the phosphorylation and hence activation of MAP kinase p38. Pretreatment with SB-203580, a p38 inhibitor, significantly reduced MLR stimulatory capacity of CypA-induced DCs in both CD8⁺ T cells and CD4⁺ T cells (P < 0.05). Conclusions. CypA enhances DC differentiation and maturation by up regulating CD11b and CD11c expression. CypA can also augment DC antigen uptake and antigen presentation, which may be mediated by the P38 signaling pathway.     

Thymosin-α1 modulates dendritic cell differentiation from human CD14+ monocytes

Introduction. Thymosin-α1 (Tα1) has established immunomodulatory effects on T cells, NK cells, and macrophages. The objective of this study was to determine the effect of Tα1 on DC differentiation, activation, and functional maturation. Methods. CD14-positive monocytes were purified from human peripheral blood mononuclear cells (PBMC) by MACS separator. Cells were treated with GM-CSF and IL-4 in the absence or presence of Tα1 and cell-surface markers were monitored using FACS analysis. Functional endocytosis of DCs was analyzed by antigen-uptake of FITC-conjugated Dextran beads. Ability of antigen presentation of matured DCs (mDCs) was monitored using an allogeneic mixed lymphocyte reaction assay (MLR) by [³H]-thymidine incorporation. Finally, the release of Th1 and Th2 polarizing cytokines by allogeneic T cells was analyzed by Bioplex cytokine assay. Results. Tα1 up regulated the iDC surface expression of CD11c^lo and CD11b^lo by 2- and 30-fold, respectively. iDC surface costimulatory molecules CD40, CD83, and CD86 were also up-regulated about 10% by Tα1 treatment. There was about 10% of reduced antigen uptake ability by Tα1-treated iDCs. During TNF-α-induced maturation, levels of MHC class II^lo and CD4^lo markers were up regulated by 3-fold in the presence of Tα1. Furthermore, Tα1-treated mDCs increased allogeneic CD3⁺ T cell proliferation by 2-fold as compared with non-Tα1-treated mDCs. However, there were no significant differences in Th1 or Th2 types of cytokines production by allogeneic T cells stimulated by either Tα1-treated or nontreated mDCs. Conclusions. Tα1 significantly enhances the differentiation and maturation of CD14⁺ monocytes derived iDCs. Furthermore, Tα1 decreases iDCs to endocytose foreign antigens and increases mDCs capacity for antigen presentation and stimulation of allogeneic T cell proliferation. These results suggest that Tα1 exerts its immunomodulatory effects on the immune system via direct interaction with DCs.     

Neutralising antibody, CTL and dendritic cell responses to hepatitis C virus: a preventative vaccine strategy

Hepatitis C virus (HCV) accounts for the majority of cases of transfusion acquired hepatitis and hepatitis transmitted by injecting drug use. The patients who do not clear the infection become chronic carriers of HCV and form a reservoir of infection within human populations. Furthermore, these carriers are at serious risk of developing cirrhosis of the liver and hepatocellular carcinoma. The disease is of major concern in developing as well as in developed countries and yet there are no vaccines against HCV, treatment is confined to the use of chemotherapy which is expensive and not always effective. The major obstacle in vaccine development is a limited understanding of the type of immune response that is necessary for viral clearance and the occurrence of various genotypes and quasispecies of HCV. The problems are further compounded by difficulties in growing the virus in vitro and the lack of a suitable and economical animal model.     

Post-transplant lymphoproliferative disorder limited to the skin

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a condition affecting immunosuppressed transplant patients and has a variety of clinical presentations. It is rarely found in the skin, and cases of PTLD in the skin are usually linked with lymph node or other organ involvement. METHODS: We report a case of plasmacytoid PTLD that is limited to the skin. A 63-year-old man with a history of cardiac transplant presented with exophytic tumors involving the lower extremity. The diagnosis and classification of the various forms of PTLD are discussed. RESULTS: Histology, immunohistochemical stains, and in situ hybridization revealed an aggressive plasmacytoid tumor that was Epstein-Barr virus positive. The patient's tumors resolved with decreased immunosuppression and localized radiation. CONCLUSION: This case is unusual for several reasons including involvement limited to the skin, presentation 15 years following transplant, and plasmacytoid phenotype of the tumor. This disorder will likely be seen by dermatologists and dermatopathologists with the increasing use of immunosuppressive medications in the dermatologist's patient population.     

Cytoskeletal organization in tropomyosin-mediated reversion of ras-transformation: Evidence for Rho kinase pathway

Tropomyosin (TM) family of cytoskeletal proteins is implicated in stabilizing actin microfilaments. Many TM isoforms, including tropomyosin-1 (TM1), are down-regulated in transformed cells. Previously we demonstrated that TM1 is a suppressor of the malignant transformation, and that TM1 reorganizes microfilaments in the transformed cells. To investigate how TM1 induces microfilament organization in transformed cells, we utilized ras-transformed NIH3T3 (DT) cells, and those transduced to express TM1, and/or TM2. Enhanced expression of TM1 alone, but not TM2, results in re-emergence of microfilaments; TM1, together with TM2 remarkably improves microfilament architecture. TM1 induced cytoskeletal reorganization involves an enhanced expression of caldesmon, but not vinculin, alpha-actinin, or gelsolin. In addition, TM1-induced cytoskeletal reorganization and the revertant phenotype appears to involve re-activation of RhoA controlled pathways in DT cells. RhoA expression, which is suppressed in DT cells, is significantly increased in TM1-expressing cells, without detectable changes in the expression of Rac or Cdc42. Furthermore, expression of a dominant negative Rho kinase, or treatment with Y-27632 disassembled microfilaments in normal NIH3T3 and in TM1 expressing cells. These data suggest that reactivation of Rho kinase directed pathways are critical for TM1-mediated microfilament assemblies.