Compartment syndrome due to extravasation of peripheral parenteral nutrition: extravasation injury of parenteral nutrition / 소아과

Compartment syndrome is a rare but devastating condition that can result in permanent neuromuscular or soft tissue injuries. Extravasation injuries, among the iatrogenic causes of compartment syndrome, occur under a wide variety of circumstances in the inpatient setting. Total parenteral nutrition via a peripheral route is an effective alternative for the management of critically ill children who do not obtain adequate nutrition via the oral route. However, there is an inherent risk of extravasation, which can cause compartment syndrome, especially when detected at a later stage. Herein, we report a rare case of compartment syndrome and skin necrosis due to extravasation, requiring emergency fasciotomy and skin graft in a 7-month-old boy who was treated with peripheral parenteral nutrition via a pressurized infusion pump. Although we cannot estimate the exact time at which extravasation occurred, the extent and degree of the wound suggest that the ischemic insult was prolonged, lasting for several hours. Pediatric clinicians and medical teams should carefully examine the site of insertion of the intravenous catheter, especially in patients receiving parenteral nutrition via a peripheral intravenous catheter with a pressurized infusion pump.

First Korean Family with a Mutation in TPM2 Associated with Sheldon-Hall Syndrome

Sheldon-Hall syndrome (SHS) is a rare autosomal dominant, inherited arthrogryposis syndrome characterized by multiple congenital contractures of the distal limbs. To date, four genes that encode the skeletal muscle fiber complex have been confirmed as the causative genes. Mutations in MYH3 have been identified most frequently and few cases of SHS caused by TPM2 mutations have been reported worldwide. This report describes, for the first time, a Korean family with two generations of SHS resulting from a rare TPM2 mutation, p.R133W. The affected mother and daughter manifested typical facial features of SHS including a triangular face with downslanting palpebral fissures, small mouth, high arched palate, and prominent nasolabial folds, and showed camptodactyly of fingers and deformities of feet with congenital vertical tali. Generalized myopathy with relative sparing of the slow-twitch muscle fibers was also revealed by electromyography in the affected mother.

Apoptosis Induced by Manganese on Neuronal SK-N-MC Cell Line: Endoplasmic Reticulum (ER) Stress and Mitochondria Dysfunction

OBJECTIVES: Manganese chloride (MnCl2) is one of heavy metals for causing neurogenerative dysfunction like Manganism. The purpose of this study was to determine the acute toxicity of MnCl2 using different times and various concentrations including whether manganese toxicity may involve in two intrinsic pathways, endoplasmic reticulum (ER) stress and mitochondria dysfunction and lead to neuronal apoptosis mediated by organelle disorders in neuroblastoma cell line SK-N-MC. METHODS: In the acute toxicity test, five concentrations (200, 400, 600, 800, 1,000 uM) of MnCl2 with 3, 6, 12, 24, 48 hours exposure were selected to analyze cell viability. In addition, to better understand their toxicity, acute toxicity was examined with 1,000 uM MnCl2 for 24 hours exposure via reactive oxygen species (ROS), mitochondria membrane potential, western blotting and mitochondrial complex activities. RESULTS: Our results showed that both increments of dose and time prompt the increments in the number of dead cells. Cells treated by 1,000 microM MnCl2 activated 265% (+/-8.1) caspase-3 compared to control cell. MnCl2 induced intracellular ROS produced 168% (+/-2.3%) compared to that of the control cells and MnCl2 induced neurotoxicity significantly dissipated 48.9% of mitochondria membrane potential compared to the control cells. CONCLUSIONS: This study indicated that MnCl2 induced apoptosis via ER stress and mitochondria dysfunction. In addition, MnCl2 affected only complex I except complex II, III or IV activities.

The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin Induced Headache Model in Rats

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicin-induced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.

Intrapleural Chemotherapy with Cisplatin and Cytarabine in the Management of Malignant Pleural Effusion / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the efficacy of intrapleural chemotherapy (IPC) with cisplatin and cytarabine in the management of malignant pleural effusion (MPE) from non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: A prospective analysis was carried out on 40 patients with pathologically proven MPE from NSCLC who had received IPC. A single dose of cisplatin 100 mg/m2 plus cytarabine 1200 mg/m2 in 250 ml normal saline was instilled into the pleural space via a chest tube and drained 4 hours later. Patients were evaluated for toxicities and responses at 1, 2, & 3 weeks and then at monthly intervals if possible. Systemic chemotherapy was administered, if the patient agreed to receive it, after achieving complete control (CC) of MPE. RESULTS: The median duration of chest tube insertion for drainage was 7 (3~32) days. Among the assessable 37 patients, CC and partial control (PC) were 32 (86.5%) and 4 (10.8%) patients, respectively (overall response rate 97.3%). The median duration of response was 12 months (2~23) and there were only two relapses of IPC after achieving CC. Among the 35 patients who were assessable until they died, 28 patients (80.0%) maintained CC until the last follow-up. There was only one toxic death and the toxicities of IPC, versus the results obtained, were deemed acceptable. CONCLUSION: The procedures were tolerable to the patients and chemotherapy-induced complications were at an acceptable level. The outcome of this trial indicates that IPC has a superior and long lasting treatment response in the management of patients with MPE from NSCLC.

The Effectiveness of IL-12 Administration and Fusion on Tumor Antigen Sensitization Methods for Dendritic Cells Derived from Patients with Myelogenous Leukemia

BACKGROUND: Immunotherapy using dendritic cells (DC) loaded with tumor antigens may represent a potentially effective method for inducing antitumor immunity. We evaluated the effectiveness of DC-based antitumor immune response in various conditions. METHODS: DC were cultured from peripheral blood mononuclear cells (PBMNC) in myelogenous leukemia (ML) and lysates of autologous leukemic cells are used as tumor antigen. The effectiveness of interleukin-12 (IL-12) and CD40L (CD154) on the antigen presenting function of lysates-loaded DC was analyzed by proliferation, cytokine production, and cytotoxicity tests with activated PBMNC (mainly lymphocytes). For generating antigen-loaded DC, direct fusion of DC with ML was studied. RESULTS: Antigen loaded DC induced significantly effective antitumor immune response against autologous leukemic cells. Administration of IL-12 on the DC based antitumor immune response showed higher proliferation activity, IFN-gamma production, and cytotoxic activity of PBMNC. Also, fused cell has a potent antitumor immune response. CONCLUSION: We conclude that lysates-loaded DC with IL-12 may be effectively utilized as inducer of antitumor immune reaction in ML and in vivo application with DC-based antitumor immunotherapy or tumor vaccination seems to be feasible.

A Study of Effective Unified Medical Language System Concept Indexing in Radiology Reports / 대한의료정보학회지

OBJECTIVE: For the effective retrieval of clinical information, the elaborate indexing is essential. Two major types of indexing are the human indexing and the automatic or machine indexing. Human indexing shows higher quality but is time consuming, labor-intensive and inconsistent in term assignment activity. METHODS: Using the Unified Medical Language System (UMLS) MetaMap program, we mapped the free text from the diagnosis section of radiology reports into UMLS concepts. To improve the precision of UMLS concept indexing by MetaMap, we evaluated the UMLS subset mapping and semantic type filtering methods, determining the best combination for improved precision. RESULTS: After calculating the candidates from subset combinations, we obtained more enhanced results by semantic-type filtering. CONCLUSION: The results may be improved for the complete automation of indexing process.

The Effect of Mesenchymal Stem Cells on the Activation of Dendritic Cells in the Cell Culture Insert System

BACKGROUND: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigen- presenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. METHODS: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. RESULTS: MSC inhibit the CD83 and HLA- class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-gamma production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. CONCLUSION: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.

Myelodysplastic Syndrome with Erythroid Aplasia following Pure Red Cell Aplasia

Myelodysplastic syndrome (MDS) with erythroid aplasia is a very rare disorder that has not been clearly defined. We experienced a case of pure red cell aplasia (PRCA), which evolved to MDS with erythroid aplasia. A 59-year-old male with transfusion-dependent PRCA was referred to our hospital for an evaluation of newly developed thrombocytopenia. Two years ago, PRCA was diagnosed by the laboratory findings and a bone marrow examination, which showed no evidence of any myelodysplastic features and thymoma. Upon admission, the bone marrow findings showed marked hypercellularity. with numerous dysplastic features in the three lineages including erythroid hypoplasia. These findings were compatible with a diagnosis of MDS with red cell aplasia. It is very interesting that the PRCA evolved to MDS with red cell aplasia, which strongly suggests an autoimmune mechanism for the development of MDS.

Regulation of 3HNorepinephrine Release by Opioids in Human Cerebral Cortex

To investigate the receptors mediating the regulation of norepinephrine (NE) release in human cerebral cortex slices, we examined the effects of opioid agonists for mu-, delta-, and kappa -receptors on the high potassium (15 mM) -evoked release of [3H]NE. [3H]NE release induced by high potassium was calcium-dependent and tetrodotoxin-sensitive. [D-Pen2, D-Pen5]enkephalin (DPDPE) and deltorphin II (Delt II) inhibited the stimulated release of norepinephrine in a dose-dependent manner. However, Tyr-D-Ala-Gly- (Me) Phe-Gly-ol and U69, 593 did not influence the NE release. Inhibitory effect of DPDPE and Delt-II was antagonized by naloxone, naltrindole, 7-benzylidenaltrexone and naltriben. These results suggest that both delta 1 and delta 2 receptors are involved in regulation of NE release in human cerebral cortex.

Membranous Nephropathy after Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Aplastic Anemia: A Case Report

Nephrotic syndrome has been described as one of the clinical forms of chronic graft-versus-host disease (cGVHD), but a limited number of cases have been described. We experienced a young female patient with nephrotic syndrome developed 22 months after allogeneic hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia. She had been well after successful management for gut-limited cGVHD until she developed a clinical nephrotic syndrome with hypoalbuminemia of 2.0 g/dL and 24-hr urine protein of 6.88 g/dL. On physical examination and laboratory findings, there was no other evidence of cGVHD. Clinical and renal biopsy findings were consistent with cGVHD-related membranous nephropathy, and immunosuppressive agents with cyclosporine and prednisone were prescribed. After 3 month of treatment, the proteinuria decreased to normal range; and the patient from nephrotic syndrome nearly recovered. We recommend cGVHD-related glomerulonephritis should be considered in all patients with hypoalbuminemia following allogeneic HSCT, even if there is no other evidence of clinical GVHD.

Resting and Acetazolamide-Challenged Technetium 99m-ECD SPECT in Transient Global Amnesia

BACKGROUND AND OBJECTIVE: Transient global amnesia(TGA) is a neurological syndrome affecting preferentially middle-aged or elderly people and characterized by sudden onset of transient impairment of antegrade amnesia with variably retrograde amnesia. TGA was defined over 30 years ago, but the etiology remain unclear. Several mechanisms have been proposed, including arterial thromboembolic ischemic attacks in both posterior cerebral artery territories, epilepsy, and migraine. Although many studies have reported TGA, only a few reported cerebral perfusion studies using SPECT because of the brief duration of the episode. Technetium-99m-ethyl cysteinate dimmer(ECD) is superior to sensitivity of lesion detection and lesion to normal contrast, probably due to lower back diffusion from the brain to the blood and its excellent radiochemical stability. So we evaluate pathophysiologic mechanism of TGA by using 99mTC-ECD SPECT with or without acetazolamide(ACZ) stress. METHODS: We evaluated six patients with transient global amnesia, four women and two men, age ranges 56 to 78 years, mean 62.2 years. Measurements of CBF and vascular reserve using 99mTC-ECD with or without ACD stress were performed during or after TGA episode. RESULTS: One patient, who was evaluated in TGA episode showed that regional cerebral blood flow was decreased in both anteroinferior frontal, both temporal, right thalamus, both inferior parietal and left parietal region with impaired vascular reserve in left inferior temporal and right thalamus. Others, who were evaluated more than 6days in TGA episode showed that regional cerebral blood flow was decreased in left temporal (4), both temporal region (1), left thalamus (2) and both basal ganglia (1) with preserved vascular reserve except one, showed impaired vascular reserve in left thalamus. CONCLUSION: This result show that severe hypoperfusion of bilateral temporal region and impaired vascular reserve in left temporal region in TGA episode. Other patients who were recovered from TGA showed hypoperfusion of left temporal region and preserved vascular reserve. 99mTc-ECD with acetazolamide SEPCT that sensitively detects localized impaired cerebraovascular reserve should help elucidate these processes. But further study with more cases is necessary for evaluation of pathophysiology of TGA.

A case of primary pulmonary Hodgkin's disease / 대한내과학회지

Primary pulmonary involvement of Hodgkin's disease is unusual, and can be distinguished from nodal Hodgkin's disease involving the lung secondarily. We report a case of with primary pulmonary manifestation of Hodgkin's disease in young woman who survived 2 years after diagnosis with literature reviews. She had unilateral cavitating lung lesions. After pathological examination, we diagnosed as primary pulmonary Hodgkin's disease, mixed cellularity type and treated with conventional chemotherapy and adjuvant radiation.

A Patient with Epstein-Barr Virus-associated B-cell Anaplastic Large Cell Lymphoma and Human Immunodeficiency Virus Infection / 대한혈액학회지

Epstein-Barr virus (EBV), a human lymphotropic herpesvirus, is presently the best known viral contributor to the development of human lymphomas and transforms normal resting B cells into immunoblasts. Especially a positive correlation has been found between the EBV- associated lymphadenopathy and the later development of EBV-carrying lymphoma in patients with acquired immune deficiency syndrome. Anaplastic large cell lymphoma(ALCL) is a clinicopathologically distinct category of non-Hodgkin's lymphoma (NHL) and classified as T-/null-cell type lymphomas in the revised European-American Classification of lymphoid neoplasms. We report a patient with EBV- associated B-cell ALCL and HIV positive. EBV-associated ALCL in HIV-positive patient usually has B-cell phenotype, so this lymphoma should be distinguished from the classical ALCL as were defined by the revised European-American Classification of lymphoid neoplasms.

The Relationship between Clinical Drug Sensitivity and Expression of Drug Resistance Genes in Patients with Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: The occurrence of drug resistance (DR) is one of the obstacles in the successful chemotherapeutic treatment of cancer. Multidrug resistance-1 (MDR-1), multidrug resistance associated protein (MRP), topoisomerase IIalpha (Topo IIalpha) and cytidine deaminase (CDA) have been reported to be genes associated with DR in acute myelogenous leukemia (AML). But the relationship between drug sensitivity and expression of DR genes in AML has not been well defined. We investigated the expression of those DR genes in AML, at diagnosis and in relapse, with the assessment of clinical response. METHODS: Leukemic cells isolated from bone marrow of 20 patients with AML [complete remission (CR); 10, non-CR; 10] and 10 patients with non-malignant hematological diseases as control. The expression level of DR genes was determined by reverse transcription polymerase chain reaction (RT-PCR) and as sessed semiquantitatively as the optical density ratio of PCR product of the target gene to that of beta2-microglobulin (beta2-MG). RESULTS: The results are as follows. 1) The expression of DR genes was not different between CR and control group. 2) The expressions of MDR-1 and MRP in non-CR group were significantly higher than those of CR and control group (P<0.05), but there were no differences in Topo IIalpha and CDA. 3) In several relapsed cases after CR, the expressions of all of those DR genes in relapse were much increased as compared with those at diagnosis. CONCLUSION: RT-PCR and semiquantitative assessment of DR genes in AML shows that the increased expression of MDR-1 and MRP is a poor prognostic factor in the chemotherapy of AML. The development of effective strategy to suppress the increased expression of those genes, especially in relapsed AML, should be required.

A case of basophilic crisis in a patient with chronic myelogenous leukemia / 대한내과학회지

Chronic myelogenous leukemia (CML) is a clonal disorder of pluripotent hematopoietic stem cell. Transformation of CML can take place at different stages of stem cell development. The common terminal event in CML is blastic crisis in the majority of cases. Basophilic crisis of CML is very rare event and we experienced a case in 48-year-old patient with philadelphia chromosome positive CML. He had received conservative treatment for 3 years. In the basophilic crisis phase, the WBC count was 64,800 /mm3 with 70 % basophils in the peripheral blood and 43.6% in bone marrow. These basophils had left-shifted maturation. Cytogenetic study revealed the philadelphia chromosome without other abnormalities.

Expression of P53, Bcl-2, Bax, and P-glycoprotein in Relation to Chemotherapeutic Response in Patients with Advanced Non-Small-Cell Lung Cance / 대한암학회지

PURPOSE: To evaluate the relationship between the expressions of p53, bcl-2, bax, and p-glycoprotein and the chemotherapeutic response seen in patients with advanced NSCLC. MATERIALS AND METHODS: Forty-four patients pathologically proven as NSCLC were reviewed. They had undergone at least two cycles of the same chemotherapeutic agents (cisplatin 60 mg/m2 day 1+ vinorelbine 25 mg/m2 day 1, 8, 21-day cycle) and the clinical response was evaluated by WHO criteria. The expressions of p53, bcl-2, bax, and p-glycoprotein were determined by immunohistochemistry. RESULTS: Patients recorded as CR (2/44) and PR (20/44) were classified as the responder group (22/44) and stable (17/44) and progression (5/44) as the non-responder group (22/44). Positive expression of p53, bcl-2, bax, and p-glycoprotein were 84.1%, 65.9%, 88.6%, and 61.4% respectively. The expression score of p53 was significantly higher in the non-responder group than that seen in the responder group (8.59+/-1.89 vs 5.32+/-2.15, p<0.05). However, the expression scores of bcl-2, bax, and p-glycoprotein were not significantly correlated with the clinical response. CONCLUSION: This study suggests that p53 gene mutation plays an important role in the clinical response to chemotherapy including cisplatin and vinorelbine. In future investigations, the correlation with the survival time will be studied.

In vitro Culture of Dendritic Cells and Activation of Peripheral Blood Mononuclear Cells in Patients with Chronic Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells whose function is to present antigen to naive T cells and play a cental role in the induction of T- cell and B-cell immunity in vivo. Immunotherapy using DCs loaded with tumor antigens may represent a potentially effective method of inducing antitumor immunity in patients with cancer. We evaluated the possibility of adoptive immunotherapy using in vitro-generated dendritic cells (DCs) and activated mononuclear cells (mainly T lymphocytes) with cytotoxic activity against autologous malignant cells in patients with Philadelphia chromosome and chimeric p210 bcr-abl fusion protein positive chronic myelogenous leukemia (CML). METHODS: DCs were cultured from peripheral blood adherent cells in the presence of GM-CSF and interleukin-4 and the morphology and immunophenotype of the cultured DCs were determined by light micro- scope and flow cytometry. As functional assays of DCs, the stimulatory function of mononuclear cells against allogeneic mononuclear cells and autologous tumor cell lysat-es were studied in co-culture reaction. Also, the cytotoxic activity of mononuclear cells against autologous malignant cells were examined using LDH release test. RESULTS: The cultured cells have higher levels of CD40, CD80, CD86, and MHC class II fluorescence intensity, which are markers of DCs, after culture as compared with those before culture. These cells were potent stimulators in the proliferative response of mononuclear cells in allogeneic co-culture reaction and in the proliferative response against autologous tumor lysates. Also, autologous mononuclear cells stimulated with in vitro-generated DCs pulsed with autologous tumor lysates displayed cytotoxic activity against autologous tumor cells. CONCLUSION: We concluded that in vitro- generated DCs can be effectively utilized as inducer of antitumor immune reaction in CML and further in vivo applications with DCs- based antitumor immunotherapy seems to be feasible.

A Case of Hairy Cell Leukemia / 대한혈액학회지

Hairy cell leukemia (HCL) is a chronic B- cell disorder characterized by the presence of typical hairy cells in the peripheral blood and marrow, pancytopenia, and a variable degree of splenomegaly. Identification of typical hairy cells in the peripheral blood and demonstration of tartrate-resistant acid phosphatase (TRAP) are critical findings in HCL. Hepatic involvement of HCL is a common feature and liver biopsy show diffuse mono-nuclear cell infiltration throughout the hepatic sinusoids and in the portal areas. We report a case of hairy cell leukemia in a 52-year-old man who presented with pneumonia and hepatic infiltration with review of the literatures.

A case with mucosa-associated lymphoid tissue(MALT) lymphoma and tuberculous enteritis at jejunum / 대한내과학회지

Mucosal-associated lymphoid tissue(MALT) lymphoma is derived from the marginal zone B-cell compartment and can be found at wide variety of extranodal sites, most frequently at the gastrointestinal sites. Recent clinicopathologic studies suggest a relationship between MALT lymphoma and chronic inflammatory disorders, such as Helicobacter pylori infection in stomach or autoimmune disorders, such as Sj gren's syndrome in salivary glands. Primary gastrointestinal MALT lymphoma most commonly arises in the stomach and less often in the small and large intestine. Recently we experienced a case who had MALT lymphoma and tuberculous enteritis at the same site (jejunum) confirmed by exploratory laparotomy.