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.     

Intrahepatic CD8+ T-lymphocyte response is important for therapy-induced viral clearance in chronic hepatitis B infection

BACKGROUND/AIMS: To determine which immune cells contribute to HBV-clearance during antiviral therapy, we performed a longitudinal analysis of intrahepatic immune cells during interferon-alpha therapy of chronic HBV-patients using the FNAB technique. METHODS: Twenty chronic HBeAg+-patients were treated with pegylated alpha-interferon combined with lamivudine or placebo for 52 weeks. FNAB and blood specimens were obtained at week 0, 2, 8 and 52. CD4+- and CD8+ T-lymphocytes, CD56+ cells, IFNgamma and granzyme B (GrB) were immunocytochemically quantified. RESULTS: The relative numbers of CD56+ cells and CD8+ T-lymphocytes were significantly higher in FNAB compared to blood at all time-points. Responders (n=9) exhibited significant increases in intrahepatic CD8+ and CD8+GrB+ lymphocytes, a small elevation in CD8+IFNgamma+ T-lymphocytes, no change in CD4+ T-lymphocytes, and a decrease in intrahepatic CD56+ cells during the first weeks of therapy. In non-responders (n=11) no significant changes in CD4+- and CD8+ T-lymphocytes and an increase in intrahepatic and CD56+ cells were observed during therapy. CONCLUSIONS: The intrahepatic CD8+ T-lymphocyte, but not the CD4+ T-lymphocyte or NK/NKT-cell response, is important for HBV clearance during interferon-alpha therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms.     

Neuromorbidity in preterm twins in relation to chorionicity and discordant birth weight

OBJECTIVE: The purpose of this study was to determine the incidence of neurologic morbidity in preterm monochorionic (MC) and dichorionic (DC) twins. STUDY DESIGN: We collected perinatal, neonatal, and infant follow-up data of 76 MC and 78 DC twins born between 24 and 34 weeks of gestation (295 infants). Risks of neuromorbidity in the surviving infants were evaluated in relation to chorionicity, discordant birth weight (>20%), twin-twin transfusion syndrome (TTTS), and cotwin death. RESULTS: The overall incidence of cerebral palsy and minor neurologic disabilities in surviving twins was 4% and 9%, respectively. MC infants had a higher incidence of cerebral palsy (8% vs 1%, P<.05) and neurologic morbidity (15% vs 3%, P<.05) than DC infants. The risk of impaired neurodevelopment was higher in MC infants with discordant birth weight (42%, P<.01), TTTS (37%, P<.01), and cotwin death (60%, P<.01) than those with concordant birth weight (8%). In MC pregnancies, the cerebral palsy risk was higher in infants with discordant birth weight than those with chronic TTTS (19% vs 4%, P<.05). Similarly, discordant DC infants had higher neuromorbidity than concordant group (5% vs 1%, P<.05). In both MC and DC discordant infants, neurologic morbidity was independent of growth restriction. CONCLUSION: Neurologic morbidity in the preterm MC infants was 7-fold higher than DC infants because of chronic TTTS, discordant birth weight, and cotwin death in utero.     

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.