Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute lymphocytic leukemia

Mucormycosis is a rare but invasive opportunistic fungal infection with increased frequency during chemotherapy-induced neutropenia. The clinical infections due to Mucor include rhinocerebral, pulmonary, cutaneous, gastrointestinal and disseminated diseases. The first two are the most common diseases and all entities are associated with a high mortality rate. Still hepatic involvement of Mucor is rarely reported. We experienced a case of hepatic and small bowel mucormycosis in a 56-year-old woman after induction chemotherapy for B-cell acute lymphocytic leukemia. Initial symptoms were a high fever unresponsive to broad spectrum antibiotics and pain in the left lower abdominal quadrant. It was followed by septic shock, deterioration of icterus and progressively elevated transaminase. An abdominal CT demonstrated multiple hypodense lesions with distinct margins in both lobes of liver and pericolic infiltration at small bowel and ascending colon. Diagnosis was confirmed by biopsy of the liver. The histopathology of the liver showed hyphae with the right-angle branching, typical of mucormycosis. The patient was managed with amphotericin B and operative correction of the perforated part of the small bowel was performed. However, the patient expired due to progressive hepatic failure despite corrective surgery and long-term amphotericin B therapy.     

Veno-occlusive disease (VOD) of the liver in Korean patients following allogeneic bone marrow transplantation (BMT): efficacy of recombinant human tissue plasminogen activator (rt-PA) treatment.

Veno-occlusive disease (VOD) of the liver is a clinical syndrome characterized by hyperbilirubinemia, painful hepatomegaly, and fluid retention. In the bone marrow transplantation (BMT) setting, VOD is caused by dose-intensive chemotherapy and/or radiotherapy used to prepare patients for transplant. VOD occurs in up to 50% of the patients who undergo BMT and is usually associated with a high mortality rate. Until recently, there was no proven effective medical therapy for this condition once it was clinically apparent. We report here on the frequency and treatment result of VOD with rt-PA in our allogeneic BMT patients. Eight patients (median age 28.5 years) underwent allogeneic BMT from December, 1993 to June, 1995 in Asan Medical Center. Six leukemia patients were prepared for BMT with busulfan and cyclophosphmide, while two aplastic anemia patients received cyclophosphamide and antithymocyte globulin. VOD was defined as having two of the following features before day 20 posttransplant: jaundice (bilirubin > or = 2 mg/dL), tender hepatomegaly and/or right upper quadrant pain, ascites and/or unexplained weight gain (> 2% from baseline). All patients who were diagnosed with VOD received rt-PA (10-20 mg/day) and heparin (10,000 U/day). Three (37.5%) of the eight patients developed VOD that occurred between 6 and 10 days posttransplant. All three patients developed jaundice, weight gain, and tender hepatomegaly. Ascites and renal insufficiency occurred in two patients and pleural effusion in one patient. rt-PA and heparin were begun 6 to 26 days posttransplant and rt-PA was administered for 7 to 14 days. All three patients responded to the therapy; bilirubin levels began to decrease at 4 to 13 days from the start of therapy. They are all alive at day 111, 316, and 548 days posttransplant. None of the patients had significant hemorrhagic complications after rt-PA treatment. Prolonged administration of rt-PA was feasible without bleeding episode and it seems that rt-PA may alter the natural course of VOD.     

An explanation of renal hemodynamics in acute renal failure based on sequential CT in patients with Korean hemorrhagic fever

The pattern of renal enhancement and washout of contrast medium was observed on sequential follow-up CT in 12 patients with Korean hemorrhagic fever, in which acute renal failure is one of the most important clinical features. Renal contrast enhancement and contrast medium washout were delayed longer in patients with severe oliguric renal failure. The delayed washout peaked at 4-5 days and did not return to normal until 8-9 days in the patients with severe oliguria; in the patients without severe oliguria the times were 1-2 days and 3-4 days, respectively. A characteristic "cart-wheel" pattern was observed during the washout stage in patients without severe oliguria. This "cart-wheel" pattern of washout is thought to result from relief of vasoconstriction and repair of tubular function. Multifocal "wedge-shaped" nonenhanced areas of the kidney, seen on the 2 week follow-up postcontrast CT, are thought to be ischemic zones due to persistent vasoconstriction. On the 6 week follow-up postcontrast CT in one patient, scarring of the kidney was detected in the same area that did not enhance on the 2 week CT. This scarring is thought to be a result of permanent vasoconstriction.     

Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.     

GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis

The quality of articular cartilage engineered using a cell-polymer construct depends, in part, on the chemical composition of the biomaterial and whether that biomaterial can support the chondrocytic phenotype. Acknowledging the supportive influence of tissue-specific matrix molecules on the chondrocytic phenotype, we have combined chondroitin sulfate-A (CSA) and chitosan, a glycosaminoglycan (GAG) analog, to develop a novel biomaterial to support chondrogenesis. Chitosan is a polycationic repeating monosaccharide of beta-1,4-linked glucosamine monomers with randomly located N-acetyl glucosamine units. Chitosan may be combined with the polyanionic CSA such that ionic crosslinking results in hydrogel formation. Bovine primary articular chondrocytes, when seeded onto a thin layer of CSA-chitosan, form discrete, focal adhesions to the material and maintain many characteristics of the differentiated chondrocytic phenotype, including round morphology, limited mitosis, collagen type II, and proteoglycan production. Our findings suggest CSA-chitosan may be well suited as a carrier material for the transplant of autologous chondrocytes or as a scaffold for the tissue engineering of cartilage-like tissue.     

A case of leukemia-associated arthritis--identification of leukemic cells in synovial fluid by light microscopy

One case of arthritis complicating leukemia is described in which leukemic cells were identified in synovial fluid by light microscopy. Although arthritis is a well-known manifestation of leukemia with an incidence of 13.5%, the pathogenesis often is unclear, and the direct demonstration of leukemic cells in synovial fluid has been very uncommon. A 16 year-old male patient was admitted due to left elbow joint pain and swelling. Synovial fluid examination revealed blast cells and this finding has directed to a final diagnosis of acute lymphoblastic leukemia.     

Preclinical evaluation of prototype products

Preclinical evaluation of medical devices (prototype products) offers the opportunity to investigate and study the intended use of device materials. Preclinical evaluation programs are designed to determine the efficacy, safety, and biocompatibility of biomaterials, prostheses, and medical devices. The purpose of safety testing is to determine if a material presents potential harm to the human; it evaluates the interaction of the material with the in vivo environment and determines the effect of the host on the implant. Preclinical evaluation is the determination of the ability of the prototype product to perform with appropriate host response in a specific application, considered from the perspective of human clinical use. Therefore, preclinical data should include materials science and engineering, biology, biochemistry, medicine, host reactions and their evaluation, the testing of biomaterials, and the degradation of materials in a biological environment.     

The role of radiotherapy in the treatment of aggressive fibromatosis

Aggressive fibromatosis is a rare benign soft tissue tumor that is difficult to cure because of its infiltrative nature and high tendency to recur locally. The authors retrospectively analyzed 20 patients with histologically-confirmed fibromatosis. All patients underwent surgery with a wide or marginal margin. Five (25%) cases with histologically-negative margins had recurred. External beam radiotherapy was administered to patients whose margins were positive or who had local recurrence. However, out of concern for safety, radiotherapy was not given to two babies and a reproductive-aged woman. The average dose was 5,020 cGy. During the follow-up (mean 32.6 months), all the patients undergoing radiotherapy showed no evidence of local recurrence. A wide local excision has traditionally been the treatment of choice. However, postoperative radiotherapy could be an effective measure for preventing local recurrence in patients with a histologically-positive surgical margin and recurrence independent of any signs of relapse.     

Differential modulation by baclofen on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the formalin test

Our previous studies have demonstrated that supraspinal GABAergic receptors are differentially involved in the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) in the tail-flick and hot-plate tests. These two models employed a phasic, thermal nociceptive stimulus. The present study was designed to examine the possible involvement of supraspinal GABAergic receptors in opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed the almost complete inhibitory effects against the hyperalgesic response in both phases. Muscimol (75-100 ng) and baclofen (5-10 ng) injected i.c.v. produced the hypoalgesic response in the both phases. The hypoalgesic response induced by muscimol and baclofen observed during the second phase was more pronounced than that observed during the second phase. Baclofen (2.5 ng), at the dose which did not affect the hyperalgesic response, resulted in a significant reversal of the i.c.v. administered beta-endorphin-induced hypoalgesic response observed during the second, but not the first, phase. However, the hypoalgesic response induced by i.c.v. administered morphine was not changed by the same dose of muscimol or baclofen injected i.c.v. Our results indicate that, at the supraspinal level, GABA(B)receptors appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin test model.     

Central core disease--a case report.

Central core disease is a rare congenital myopathy characterized by the formation of "cores" that consist of abnormal arrangement of myofibrils inside the myofibers. We report a 5-year-old Korean girl who showed a fairly typical clinical course of non-progressive muscle weakness. Electrodiagnostic studies showed low-amplitude polyphasic electromyograph and normal nerve conduction velocity. Gastrocnemius muscle biopsy showed central cores in over 80% of the fibers on H&E section. Histochemistry revealed deficient or absent mitochondrial enzyme in the cores and type I predominance. Ultrastructurally both structured and non-structured cores were found separately or simultaneously in one fiber. This case is the first report in the Korean literature.