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Rare presentation of intestinal amyloidosis with acute intestinal pseudo-obstruction and perforation Gastrointestinal manifestations of amyloidosis include dysmotility and pseudo-obstruction. Here, we report an exceptional case of acute small bowel obstruction [...]

Following acute-phase infection, activated T cells are terminated to achieve immune homeostasis, failure of which results in lymphoproliferative and autoimmune diseases. We report that sterile α- and heat armadillo-motif-containing protein (SARM), the most conserved Toll-like receptors adaptor, is proapoptotic during T-cell immune response. SARM expression is significantly reduced in natural killer (NK)/T lymphoma patients compared with healthy individuals, suggesting that decreased SARM supports NK/T-cell proliferation. T cells knocked down of SARM survived and proliferated more significantly compared with wild-type T cells following influenza infection in vivo. During activation of cytotoxic T cells, the SARM level fell before rising, correlating inversely with cell proliferation and subsequent T-cell clearance. SARM knockdown rescued T cells from both activation- and neglect-induced cell deaths. The mitochondria-localized SARM triggers intrinsic apoptosis by generating reactive oxygen species and depolarizing the mitochondrial potential. The proapoptotic function is attributable to the C-terminal sterile alpha motif and Toll/interleukin-1 receptor domains. Mechanistically, SARM mediates intrinsic apoptosis via B cell lymphoma-2 (Bcl-2) family members. SARM suppresses B cell lymphoma-extra large (Bcl-xL) and downregulates extracellular signal-regulated kinase phosphorylation, which are cell survival effectors. Overexpression of Bcl-xL and double knockout of Bcl-2 associated X protein and Bcl-2 homologous antagonist killer substantially reduced SARM-induced apoptosis. Collectively, we have shown how T-cell death following infection is mediated by SARM-induced intrinsic apoptosis, which is crucial for T-cell homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: Congenital tracheal stenosis is a rare but life-threatening obstructive airway disease. It usually presents in early infancy and requires surgical intervention. This study is a review of our experience in the management of congenital tracheal stenosis in children at KK Women's and Children's Hospital, Singapore., Methods: All children who had undergone tracheoplasty for congenital tracheal stenosis between January 1999 and December 2008 were included. The patients' medical records were retrieved from our database, and the demographic data, comorbidities, clinical presentation and management, surgery performed, postoperative complications, final outcomes and follow-up were reviewed., Results: A total of 11 children aged 12 days to six years underwent surgery for congenital long-segment tracheal stenosis, of which ten (90.9 percent) had associated cardiac and vascular anomalies and nine (81.8 percent) had left pulmonary artery sling predominance. Five (45.4 percent) children had associated bronchopulmonary abnormalities. All the patients underwent slide tracheoplasty with concomitant repair of congenital heart defects. Overall mortality was 45.4 percent (n is 5), including one late mortality due to an unrelated cause. With the exception of one, the follow-up of all patients was complete at this writing. One patient had mild residual tracheal stenosis and another had bilateral bronchomalacia., Conclusion: This is the largest case series of congenital long-segment tracheal stenosis reported in Southeast Asia to date. Slide tracheoplasty with concomitant repair of cardiac lesions is currently the preferred management for long-segment stenosis. Management of such patients remains a challenge for clinicians and the patients' families, and requires a multidisciplinary approach.

A nine-year-old boy presented with increasingly worsening right shoulder pain of 18 months' duration. On physical examination, there was a tender firm swelling over the right upper arm. Radiographs showed a large osteolytic lesion in the proximal humeral diaphysis, with prominent mixed acute-on-chronic periosteal reaction in a lamellar fashion. There was a pathological fracture. The lesion appeared to be radiographically aggressive in nature. Bone scintiscan showed solitary marked uptake. On-table frozen section histopathological examination of the lesion showed an osteoblastic lesion with aggressive features. Completion curettage and high speed burring of the cavity was performed. In view of the patient's young age, which required a biological solution, and potential for local recurrence, that necessitated a radiopaque filler, the lesion was packed with a calcium phosphate cement paste. The final diagnosis was osteoblastoma with aggressive features. The patient remained well on follow-up to date. The filler continues to be remodelled to native tissue and there is no evidence of local recurrence. Osteoblastoma is a relatively rare benign tumour that typically occurs in the posterior elements of the vertebral column. The humerus is a very rare site of disease in the appendicular skeleton, and poses a diagnostic dilemma which implicates the possibility of osteogenic sarcoma.

Background: We undertook an audit of paediatric perioperative incidents in the first 10000 anaesthetics administered in KK Women's and Children's Hospital in Singapore between May 1997 and April 1999. The spectrum of surgery performed ranged from simple ambulatory surgery to open heart surgery for complicated congenital heart diseases., Methods: An audit form is completed for every anaesthetic delivered and critical incidents are reported on the reverse blank page of the audit form. An anaesthetic incident was defined as 'any incident which affected, or could have affected, the safety of the patient under anaesthetic care'., Results: Two hundred and ninety-seven critical incidents were reported. The majority of them happened in healthy patients (80.1% ASA I and II) scheduled for elective surgery (73.3%). Critical incidents in infants less than 1 year of age were four times as common as in older children (8.6% versus 2.1%). Incidents occurred mainly during maintenance (80.6%). There was no anaesthetic mortality. Respiratory events were the most common (77.4%) with laryngospasm accounting for 35.7%. Cardiovascular incidents (10.8%) included hypotension from haemorrhage and sepsis, and dysrhythmias. The incidence of equipment and pharmacologically related problems was low., Conclusions: Future reviews of a larger patient population may be helpful to determine trends of perioperative events and whether quality assurance programs have made a difference.

Introduction: Primitive neuroectodermal tumours (PNETs) of the chest wall are rare entities and little is known regarding its biological activity and prognostic factors. Two cases are reported and the available literature reviewed to highlight the presentation and management of these tumours., Clinical Features: We report 2 patients who were diagnosed with PNET of the chest wall in our centre. As there are no clinical features or basic diagnostic measures which are characteristic of these tumours, diagnosis is based on special tests. With the advent of newer immunohistochemical methods, it is now diagnosed more confidently., Treatment: Both patients received multidisciplinary modalities of treatment, comprising extensive surgical resection, chemotherapy and radiotherapy., Outcome: One patient succumbed to the disease one year after diagnosis and the other is currently disease-free, both clinically and radiologically at 24 months., Conclusion: Despite multidisciplinary modalities of treatment, the prognosis of PNET is still generally poor. Early diagnosis and treatment are important to improve the chances of survival.

Pulmonary metastases from choriocarcinoma can very rarely give rise to a 'miliary' pattern on the chest X-ray. A 23-year-old woman with a diffuse nodular pattern on chest X-ray died due to acute respiratory failure and cor pulmonale. At autopsy, choriocarcinoma of the uterus was found. In the lungs, multiple macrovascular tumour emboli within branches of pulmonary muscular arteries in the region of segmental/subsegmental bronchi were detected. There was no evidence of pulmonary parenchymal metastases, pneumonia or tuberculosis. The 'miliary' pattern of pulmonary metastases described in cases of choriocarcinoma may be due to large vessel intra-arterial tumour emboli rather than disseminated parenchymal metastases.

Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy (SHML) is primarily a nodal-based, idiopathic, benign proliferative disorder of histiocytes with 43% of these cases also involving extranodal sites. The breast is an unusual site of occurrence of RDD. We report two cases of this exceptional event. The first represents an intramammary nodal Rosai-Dorfman disease, while the second is an extranodal disease with sole involvement of the breast. In both, the possibility of malignancy was raised. Histological examination of the two breast lesions revealed sheets of characteristic large histiocytes displaying emperipolesis, a microscopic hallmark of this disease. Immunohistochemical and ultrastructural studies were also performed; the former showed cytoplasmic staining of histiocytes for S-100 protein, while histiocytes that engulfed lymphocytes and plasma cells were identified on electron microscopy.

Unlabelled: BACKGROUND AND AIMS OF STUDY: All current international practice guidelines recommend that treatment of acute asthma in the emergency room (ER) should be guided by the peak expiratory flow rate (PEFR). The aim of this study was to assess the efficacy of a PEFR guided protocol in treating ER asthma., Methods: We compared two different management protocols in adult asthmatics who presented to the ER with acute exacerbations. The routine protocol (RP) assessed and dispensed patients according to overall subjective and clinical response without predetermined criteria. The peak protocol (PP) used serial measurements of PEFR to guide intensity of bronchodilator treatment and fitness for hospital discharge. On the PP, a threshold PEFR of > or = 60% predicted had to be achieved before the patient could be discharged from the ER., Results: There were 79 patients in the RP group and 70 in the PP group. There was no significant difference between the two groups in baseline PEFR, PEFR after treatment and percentage increase in PEFR with treatment. The PP resulted in a higher hospital admission rate than RP., Conclusion: We conclude that in the management of acute asthma in the ER, a PEFR guided protocol neither improved overall PEFR response to treatment nor reduced admission rates when compared with current management as it is practised in Singapore.

Although tumor necrosis factor (TNF) and interleukin-1 (IL) induce the expression of the IL-8, TNF-stimulated gene 6, and plasminogen activation inhibitor-2 genes and the activation of NF-kappa B with nearly identical kinetics, the two cytokines differ significantly in the induction of the IL-6 gene in all primary fibroblasts tested. IL-1 induces IL-6 gene expression after 30 min of IL-1 treatment, reaching a maximum level by 7 h, and is sustained for up to 14 h. TNF also induces the IL-6 gene expression at 30 min but the induction was low. A similar differences in the amount of IL-6 secreted was observed in the IL-1/TNF-treated cells. Measurement of IL-6 gene transcription by nuclear run-on transcription assays indicated a 4-fold higher rate of IL-6 gene transcription in IL-1-treated than in TNF-treated cells. The IL-1-induced IL-6 mRNA has a significantly longer half-life (> 6 h) compared to 30 min for TNF-treated cells. These results suggest that the induction of the IL-6 gene expression in primary human fibroblasts by TNF and IL-1 is differentially regulated at the transcriptional as well as at the post-transcriptional level.

Isoforms of heat shock protein (Hsp) 27 were used as intracellular markers to study tumor necrosis factor/interleukin-1 (TNF/IL-1) regulation of protein phosphatases in primary human fibroblasts. These isoforms were rapidly phosphorylated to varying degrees when fibroblasts were treated with either TNF, IL-1, okadaic acid, calyculin A, ARS, epidermal growth factor, fibroblast growth factor, H2O2, buthionine sulfoximine, N-ethylmaleimide, diethylmaleimide, or iodoacetate. However, inhibitors of protein kinases A and C, tyrosyl protein kinases, and general protein kinases had no effect on the enhanced phosphorylation of these isoforms in TNF, IL-1, okadaic acid, or calyculin A-stimulated cells, suggesting that the activation of protein kinases by itself is insufficient to produce these changes. Isoforms of 32P-labeled Hsp27 were dephosphorylated during cold-chases with excess phosphate in the absence but not in the presence of TNF/IL-1 or inhibitors of protein phosphatases suggesting that inactivation of protein phosphatase(s) plays a role in TNF/IL-1 signal transduction. Assays of phosphatase activity of cytosolic fractions from TNF or okadaic acid treated human fibroblasts showed an inactivation of protein phosphatase activity against the 32P-labeled Hsp27 protein substrates. In vitro assays of partially purified phosphatase activity from primary human fibroblasts with Hsp27 substrate also showed the protein phosphatase activity to be inhibited by ARS. Like okadaic acid, ARS mimics TNF in inducing specific patterns of cellular protein phosphorylation. Taken together these findings are consistent with the hypothesis that a SH-dependent protein phosphatase is inactivated during the early events of TNF/IL-1 signal transduction, hence inhibitors of protein phosphatases and SH modifying compounds can mimic the early effects of TNF/IL-1 on cells.

Primary B lymphocytes can be induced to proliferate and certain haemopoietic cell lines such as HL60 and U937 can be induced to differentiate by the addition of phorbol esters, which have been shown to activate protein kinase C. Several non-phorbol esters, such as the bryostatins, have also been shown to bind to and activate protein kinase C. Although bryostatin-1 and 12-O-tetradecanoylphorbol-13-acetate (TPA) compete for and activate protein kinase C to the same degree and with similar kinetics and also induce similar levels of expression of the CD23 cell-surface antigen, bryostatin-1 is a weak mitogen for B lymphocytes and fails to induce the differentiation of both HL60 and U937 cells. Such an outcome suggests that these two activators have different binding properties for the enzyme that have a physiological consequence which may be useful for analysing the role that protein kinase C plays in both differentiation and proliferation. Analysis of competition assays between bryostatin-1 and TPA leads us to put forward a model where protein kinase C is required to be constantly reactivated and recycled during proliferation and differentiation which can be accomplished by TPA but not by bryostatin, although we cannot exclude the differential activation of some of the sub-species of the kinase by the two agonists.

High resolution two-dimensional gel electrophoresis was used to analyze the signal transduction pathways of tumor necrosis factor (TNF-alpha) and interleukin 1 (IL-1 alpha and -beta) in human fibroblasts. Approximately 450 discrete radioactive spots were electrophoretically resolved from cytosolic extracts of cells prelabeled with 32P. At least 63 of these polypeptides exhibited significant and concordant phosphorylation or dephosphorylation in response to TNF or IL-1, despite the fact that different receptors are involved. Most of these changes concerned serine/threonine residues although enhanced tyrosine phosphorylation of several polypeptides was also observed. Phosphorylation patterns induced by a number of other agonists were compared with the patterns induced by IL-1 and TNF. These included activators of protein kinases C and A, bradykinin (a stimulator of inositol phospholipid hydrolysis), epidermal growth factor, heatshock, and mellitin (an activator of phospholipase A2). Although each of these agonists induced changes resulting in a distinct pattern of protein phosphorylation, none of these patterns had significant homology with that induced by IL-1 and TNF. Other assays were performed to verify the involvement of specific kinases. Collectively, these data indicate that IL-1 and TNF activate multiple protein kinases viz. a kinase(s) which activates microtubule-associated protein 2 (MAP-2) kinase, a kinase that phosphorylates the cap-binding protein, and a possibly novel serine/threonine protein kinase.