Immunogenicity and safety of a combined DTPa-IPV/Hib vaccine administered as a three-dose primary vaccination course in healthy Korean infants: phase III, randomized study.

We assessed the immunogenicity and safety of a three-dose primary vaccination schedule with the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Korean infants. In this phase III open-label, multicenter study (NCT01309646), healthy infants aged 42-69 days (randomized 1:1) received three doses of either pentavalent DTPa-IPV/Hib (DTPa-IPV/Hib group) or DTPa-IPV and Hib vaccines administered separately (DTPa-IPV+Hib group) at 2, 4, 6 months of age. The primary objective was to demonstrate non-inferiority of DTPa-IPV/Hib compared to DTPa-IPV+Hib vaccines in terms of immune responses to all vaccine antigens, 1 month post-dose 3. Solicited symptoms (local and general) were recorded during 4 days, and unsolicited adverse events (AEs) during 31 days, after each vaccination. Serious AEs (SAEs) were recorded throughout the study duration. The immunogenicity of the pentavalent DTPa-IPV/Hib vaccine was non-inferior compared to concomitant administration of DTPa-IPV+Hib vaccines. One month post-dose 3, nearly all infants had antibody levels above the seroprotective thresholds for anti-diphtheria toxoid, anti-tetanus toxoid, anti-polyribosyl-ribitol phosphate, and anti-poliovirus type 1, 2 and 3, and had antibody levels above the seropositive thresholds for anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies. A vaccine response for PT, FHA and PRN was observed in at least 96.7% of study participants. Anti-PRP geometric mean concentrations appeared lower for the DTPa-IPV/Hib group (8.456 µg/mL) than for the DTPa-IPV+Hib group (18.700 µg/mL). In both groups, the most common solicited symptoms were injection site redness and irritability. Fifty-seven SAEs were reported throughout the study; none were considered to be vaccination related.

Erratum: Addition of Co-Authors: Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response.

[This corrects the article e110 in vol. 33, PMID: 29573252.].

Rebound thymic hyperplasia after adrenalectomy in a patient with Cushing syndrome caused by adrenocortical adenoma: A case report.

RATIONALE: The development of rebound thymic hyperplasia (RTH) has been reported in patients who have recovered from stressful conditions such as surgery and steroid therapy. We report a case of RTH following the resolution of hypercortisolism after adrenalectomy for the treatment of adrenocortical adenoma in a patient with Cushing syndrome. PATIENT CONCERNS: A 5-month-old female infant with a history of overeating, hirsutism, and excessive weight gain for the previous 2 months was referred to the hospital. The laboratory results revealed elevated 24-hour urinary free cortisol levels. An overnight dexamethasone suppression test showed no response. Abdominal imaging revealed a right-sided suprarenal mass measuring 4_3cm. Histology showed an adrenocortical adenoma. Thus, she underwent a right adrenalectomy. DIAGNOSES: The patient showed clinical improvement with weight loss and normal cortisol levels over the next 4 months. Six months after the operation, a chest computed tomography showed enlargement of the left thymic lobe, which was previously nonexistent. INTERVENTIONS: A fine needle aspiration biopsy was performed, and histological examination revealed diffuse thymic hyperplasia. OUTCOMES: At the 1-year follow-up, the chest imaging studies showed resolution of the RTH. LESSIONS: An understanding of RTH after adrenalectomy as a treatment for cortisol-producing adrenocortical tumors is important for the prevention of unnecessary surgical intervention and therapy.

Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response.

BACKGROUND: The aggravating factors still remained unclear in inflammatory bowel disease (IBD). Despite many different therapeutic approaches, many patients do not respond to the therapy. The anti-inflammatory effect of insulin-like growth factor-binding protein-3 (IGFBP-3) was suggested because of its capability of nuclear factor-κB (NF-κB) signaling inhibition. Therefore, we hypothesized that the up-regulation of IGFBP-3 would inhibit an inflammatory process. METHODS: Lipopolysaccharides (LPS) treated intestinal epithelial cell 6 (IEC-6) and dextran sodium sulfate (DSS) induced colitis mice were used as colitis models. Exogenous IGFBP-3 expression was accomplished using the adenoviral vector system expressing IGFBP-3 (Ad/IGFBP-3). The inflammatory responses and relevant cellular responses in IEC-6 cells influenced by IGFBP-3 expression were evaluated by western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and reactive oxygen species (ROS) measurement. The severity of colitis was evaluated with the colon tissues of DSS-induced mouse model. RESULTS: We found that the IGFBP-3 expression reduced the production of inflammatory cytokines (cyclooxygenase-2, interleukin-1ß, tumor necrosis factor-α) and ROS formation. IGFBP-3 expression also induced cell viability and inhibited NF-κB activation. In line with this data, the severity of DSS-induced mouse colitis was greatly ameliorated by the treatment of IGFBP-3 expressing adenoviral particles characterized with less weight loss and preserved colon length compared with the mice treated with DSS alone. The histopathology of the colon showed the reducing signs of colitis in Ad/IGFBP-3 treated DSS-mice group. CONCLUSION: Therefore, our data suggest that Ad/IGFBP-3 up-regulation reduces colonic inflammatory response as a novel therapeutic protocol for IBD.

A Case of a Girl with Arnold-Chiari Type 1 Malformation with Precocious Puberty.

A small percentage of individuals have the neurological anomaly of central precocious puberty (CPP). Common neurologic causes of CPP include a tumor or congenital lesions. Although Arnold-Chiari malformation can be caused by congenital or acquired causes, it is unusual in patients with CPP. We present the case of a girl aged 4.5 years who complained of breast budding. Her neurological examination and growth pattern were normal. She had no endocrinological abnormality, except for true precocious puberty. We performed brain magnetic resonance imaging, which showed an Arnold-Chiari type 1 malformation. Currently, this case represents the youngest girl who exhibited both Arnold-Chiari type 1 malformation and precocious puberty. Furthermore, it is likely that there is a meaningful association between the brain lesion and precocious puberty in this case.

Awareness about past diagnosis and treatment history: nationwide survey of childhood cancer survivors and their parents.

OBJECTIVE: To assess the awareness of past medical history and long-term care issues of childhood cancer survivors (CCS) in Korea. METHODS: A nationwide survey was conducted on CCS and their parents in 10 regional cancer centers in Korea. Answers regarding cancer diagnosis and treatment history were compared with the treatment summary and categorized into three ('specific,' 'general,' and 'no') or two ('yes' and 'no') groups. RESULTS: Out of 343 contacts, 293 dyads completed the survey, and 281 dyads were analyzed. Awareness of cancer diagnosis was mostly specific for parents (76.5%) and CCS (35.2%). Awareness of anti-cancer treatment exposure was mostly general (84.6% for surgery, 67.9% for chemotherapy, and 53.9% for hematopoietic stem cell transplantation) rather than specific. In particular, more than half of the parents were not aware of the exposure to cardiotoxic agents (72.9%) or radiation therapy (56.3%). Providing information about long-term side effects and prevention of secondary cancer was significantly correlated only with more concern and more follow-up visits (P ≤ 0.001, respectively), without correlation with more specific awareness of exposure to cardiotoxic agents or radiation. CONCLUSION(S): Most of the parents of CCS were not aware of treatment-related risk factors necessary for long-term care. Providing information was significantly correlated with more concern and more follow-up visits, without improving corresponding knowledge about their past medical history. Effort aimed towards improving awareness about risk factors, the manner of providing information, and the patient referral system within which we use this information is warranted.

A Case of Cap Polyposis with Epidermal Nevus in an Infant.

Cap polyposis is extremely rare in children. We report a case of an 11-month-old male infant who visited our hospital because of rectal prolapse and small amount of hematochezia lasting several days. He also had an epidermal nevus in the sacral area. Colonoscopy showed erythematous, multilobulated, circumferential, polypoid lesions with mucoid discharge from the rectum. He was diagnosed with cap polyposis by endoscopy and histologic examination. He was treated with surgical resection, and was closely followed up. In the relevant literature, there is no report of cap polyposis in an infant. We report the first case of cap polyposis in the youngest infant.

Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas.

Rare Case of Primary Gastric Burkitt Lymphoma in a Child.

Primary gastric tumors are very rare in children. Burkitt lymphoma is a common type of non-Hodgkin's lymphoma, and gastric Burkitt lymphoma usually occurs in the aged. When involving the gastrointestinal tract, primary gastric Burkitt lymphoma is very rare in younger childhood. Many gastric lymphomas including mucosa-associated lymphoid tissue lymphoma are associated with Helicobacter pylori infection or acute bleeding symptom. We report a seven-year-old boy who presented with only some vomiting and postprandial pain. His upper gastrointestinal endoscopy and biopsy revealed a large primary Burkitt lymphoma with no acute bleeding and no evidence of H. pylori infection. After chemotherapy, he remains in remission.

Effects of cisplatin on potassium currents in CT26 cells.

AIMS: Cisplatin, a platinum-based drug, is an important weapon against many types of cancer. It is well-known that cisplatin induces apoptosis. Potassium channel plays very important role in several signaling pathways. To investigate the possibility that potassium channels also have a role in the cellular response to cisplatin, we examined the effect of cisplatin on the activity of potassium channels on CT26 cell, the colon carcinoma cell line. MATERIALS AND METHODS: The cells were cultured in DMEM, supplemented with 10< heat-inactivated fetal bovine serum. At mid-log phase, cultures were harvested, washed twice in phosphate-buffered saline, and resuspended in culture medium before use. Cells were voltage-clamped using the whole-cell patch clamp technique. Membrane current data were collected and amplified. STATISTICAL ANALYSIS: Differences between two groups were assessed by paired t-test and one sample t-test to compare the relative values. One-way ANOVA was used for all experiment with more than two groups. RESULTS: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells. CONCLUSION: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.

Simultaneous presentation of malignant peripheral nerve sheath tumor and moyamoya disease associated with neurofibromatosis type 1 in a child.

Neurofibromatosis type 1 (NF-1) is a rare hereditary disorder, which is inherited as an autosomal dominant trait. It is characterized by multiple caféau- lait spots of the skin, benign cutaneous neurofibromas, skeletal dysplasia and learning disability. The association of NF-1 with benign and malignant tumors is well established. The lifetime risk of patients with NF-1 developing malignant peripheral nerve sheath tumors (MPNSTs) has been estimated to be 8-13%. Such tumors can develop in any part of the body, but their occurrence in the gastrointestinal tract is rare. Patients with NF-1 have a wide spectrum of vascular abnormalities. Cerebrovascular lesions have been found in approximately 2.5% of children with NF1. We encountered a case of NF-1 with MPNSTs in the gastrointestinal tract and moyamoya disease.

A Gonadotropin-Releasing Hormone (GnRH) Stimulation Test Before and After GnRH Analogue Treatment for Central Precocious Puberty: Has the GnRH Test been Adequately Simplified?

OBJECTIVE: To investigate and simplify the gonadotropin-releasing hormone (GnRH) stimulation test for assessing pubertal activation and suppression. METHODS: The authors identified 72 girls diagnosed with central precocious puberty who were treated with a GnRH analogue (GnRHa). Patients who underwent an assessment regarding GnRHa-mediated puberty suppression had been diagnosed via the GnRH stimulation test prior to GnRHa treatment. The authors analyzed the diagnostic values of the during/before-treatment LH levels at different time points by a receiver-operating characteristic (ROC) curve. RESULTS: Before GnRHa treatment, the mean luteinizing hormone (LH) level was higher at the 30-min test time point than at baseline or the 15, 60, 90, and 120-min points (P < 0.001). After GnRHa treatment, the LH levels were suppressed in 62 patients (86.1%) and inadequately suppressed in 10 (13.9%). The LH level was higher at the 30-min test time point than those at baseline or the 45 and 60-min level (P < 0.001). The area under the curve in a post-GnRHa treatment was greatest at 30 min. CONCLUSIONS: The simplified GnRH test is adequate for evaluating pubertal activation (30 and/or 45-min time points of the GnRH test) and suppression (the 30-min time point).

Abdominal fibromatosis in a young child: a case study and review of the literature.

Fibromatoses comprise many different entities of well-differentiated fibroblastic proliferation with variable collagen production and form a firm nodular mass. Abdominal fibromatosis is distinguishable from other forms of fibromatosis because of its location and its tendency to occur in women of childbearing age during or following pregnancy. Abdominal fibromatosis in children is an extremely rare condition. A 15-month-old boy presented with an abdominal wall mass that had recently increased in size. Mass excision was perfomed. The tumor was 4.3×4.1 cm and partly circumscribed. Histologically, the tumor was composed of parallel long fascicles of spindle-cells with a uniform appearance. The edges of the resected mass were infiltrative, and the surgical margins were positive. Mitotic figures were <1/10 high power fields. No cellular atypia or necrosis was present. The tumor cells were positive for vimentin and nuclear ß-catenin staining.

Davallialactone from mushroom reduced premature senescence and inflammation on glucose oxidative stress in human diploid fibroblast cells.

Mushrooms are both food and a source of natural compounds of biopharmaceutical interest. The purpose of this study was to clarify whether davallialactone from mushroom extract affected the pathogenesis of hyperglycemia oxidative stress and the aging process in human diploid fibroblast (HDF) cells. The high-glucose state with glucose oxidase resulted in glucose oxidative stress, induction of inflammatory molecules, dysfunction of antioxidant molecules, and activation of mitogen-activated protein kinase (MAPKs) and its downstream signaling in old HDF cells. The exposure of glucose oxidative stress in middle-stage cells led to stress-induced premature senescence (SIPS) via senescence-associated ß-galactosidase (SA ß-gal) activity and displayed replicative senescence phenomena. However, davallialactone reduces the pathogenesis of glucose oxidative stress and the aging process through down-regulation of SA ß-gal activity. These results strongly suggest that natural compounds, especially mushroom extract davallialactone, improve the pathogenesis of glucose oxidative stress and the aging process. Hence, davallialactone has potential in the treatment of diabetes mellitus or age-related disease complications.

Nitric oxide suppresses L-type calcium currents in basilar artery smooth muscle cells in rabbits.

OBJECTIVES: Nitric oxide (NO) is well known to be a vasodilator, and NO donor compounds are currently used for treating vasospasm following subarachnoid hemorrhage. However, the action mechanism of cerebral vascular relaxation is not yet clear. L-type calcium channels have been determined to play an essential role in smooth muscle contraction. To investigate the role of L-type calcium channels in NO-induced relaxation of basilar smooth muscle cells, we examined the effect of the NO donor, sodium nitroprusside (SNP) on calcium (Ca2+) currents using smooth muscle cells isolated from a rabbit basilar artery. METHOD: The smooth muscle cells were isolated from rabbit basilar artery by enzyme treatment. To identify L-type Ca2+ currents, we used cesium chloride, a potassium channel blocker and Bay K8644, an activator of L-type Ca2+ channel. RESULTS: The L-type calcium currents (91±13.0 pA; n = 11) were significantly reduced by SNP (32±5 pA; n = 11; P<0.05). 1H-[1,2,4] Oxadiazolo [4,3-a] quinoxalin-1-one, a 3',5'-cyclic guanosine monophosphate inhibitor, blocked the effect of SNP on L-type Ca2+ currents, and similar results were obtained after the application of 7-nitroindazole, a specific NO synthase inhibitor. Furthermore, inward currents were enhanced by Bay K8644 (170±22 pA; n = 5) and were suppressed by SNP (54±13 pA; n = 5; P<0.05). DISCUSSION: These results demonstrate that NO suppresses the L-type Ca2+ currents in rabbit basilar smooth muscle cells, and suggest that L-type Ca2+ channels may play a pivotal role in NO-induced vascular relaxation.

Hispidin analogue davallialactone attenuates carbon tetrachloride-induced hepatotoxicity in mice.

In this study the protective effects of davallialactone (1), isolated from Inonotus xeranticus, have been examined against carbon tetrachloride (CCl4-induced acute liver injury. Mice received subcutaneous injection of 1 (2.5, 5, and 10 mg/kg) for three days before CCl4 injection (1 mg/kg). Protection from liver injury by 1 was confirmed by the observation of decreased serum transaminases and diminished necrosis of liver tissue. Reduced hepatic injury was very similar to that observed with silymarin, a known hepatoprotective drug used in this work for comparison. The groups treated with 1 had reduced reactive oxygen species (ROS), reduced serum malonyldialdehyde levels, and increased levels of liver Cu/Zn superoxide dismutase, as compared to the CCl4 control group. The expression of heme oxygenase-1 in the liver tissue was increased and the activity of liver cytochrome P4502E1 was restored in the mice treated with 1. In addition, levels of serum tumor necrosis factor-alpha (TNF-α), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), numbers of macrophage, and cleaved caspase-3-positive hepatocytes were reduced in the groups treated with 1. These findings suggest that davallialactone has protective effects against CCl4-induced acute liver injury, and this protection is likely due to the suppression of ROS-induced lipid peroxidation and inflammatory response.

Clinical and hematologic manifestations in patients with Diamond Blackfan anemia in Korea.

BACKGROUND: Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years. METHODS: The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study. RESULTS: The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1±1.9 g/dL, mean corpuscular volume was 93.4±11.6 fL, and mean number of reticulocytes was 19,700/mm(3). The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%). CONCLUSION: The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.

Adriamycin inhibits adipogenesis through the modulation of PPARγ and restoration of adriamycin-mediated inhibition of adipogenesis by PPARγ over-expression.

Adriamycin is an anti-cancer drug, effective against a wide range of cancers. However, its clinical application is limited by its cardiotoxicity. A number of reports suggest that adriamycin induces bodyweight loss also. The aim of this study was to investigate the effect of adriamycin on adipogenesis as bodyweight chancges can be directly correlated with adipocytes. Fat accumulation in 3T3-L1 pre-adipocytes, as a result of adipogenesis was detected using oil red O staining. We performed western immunoblot for the expression of adipocyte differentiation related genes to analyze the molecular mechanism of adriamycin-mediated inhibition of adipogenesis. Over-expression of target gene was done by using recombinant adenoviruses. Adriamycin inhibited adipogenesis in a dose-dependent manner. It was observed that adriamycin down-regulated the expression of PPARγ. Moreover, up-stream elements of PPARγ were also found to be down-regulated by adriamycin. Adriamycin might prevent bodyweight gain through inbibition of adipogenesis by the down-regulation of PPARγ and its up-stream transcriptional regulators like C/EBPß and KLF4. To reverse the adriamycin-mediated inhibition of adipogenesis, PPARγ was over-expressed by adenoviral mediated gene delivery. Over-expression of PPARγ partially restored adipogenesis. Moreover, the early regulators of adipogenesis were also found to be restored after the over-expression of PPARγ. Adriamycin down-regulates the expression of PPARγ which leads to prevention of bodyweight gain through inhibition of adipogenesis. Activation of PPARγ by either adenoviral mediated gene delivery or by using PPARγ agonist may be useful in controlling the bodyweight loss.

Magnesium sulfate suppresses L-type calcium currents on the basilar artery smooth muscle cells in rabbits.

OBJECTIVES: Although magnesium is a well-known treatment for vasospasm following subarachnoid hemorrhage, its mechanism of action for cerebral vascular relaxation is not clear. In addition, it is known that L-type calcium (Ca(2+)) channels play a pivotal role in smooth muscle contraction. To investigate the role of L-type Ca(2+) channels in the magnesium-induced relaxation of basilar smooth muscle cells, we examined the effect of magnesium sulfate on L-type Ca(2+) currents using freshly isolated smooth muscle cells from rabbit basilar arteries. METHOD: Rabbits were anesthetized with ketamine (50 mg/kg) with xylazine (25 mg/kg) and exsanguinated. Smooth muscle cells were isolated from rabbit basilar arteries by enzyme treatment. Cells were stored at 4°C before use. Whole-cell patch clamp technique was used to identify L-type Ca(2+) currents, using the potassium channel blocker, cesium chloride, and nimodipine and Bay K8644 as a blocker and activator of L-type Ca(2+) channels, respectively. RESULTS: Inward currents induced by step pulses were significantly reduced by nimodipine (n = 5, P<0·05) and increased by Bay K8644 (n = 5, P<0·05). The L-type Ca(2+) currents (122±14·0 pA, n = 12) were significantly reduced by the application of 5 mM magnesium sulfate (28±4 pA, n = 12, P<0·05). The inward currents enhanced by Bay K8644 were further suppressed by the application of magnesium sulfate. DISCUSSION: These results demonstrate that L-type Ca(2+) channels are functionally expressed in rabbit basilar smooth muscle cells and suggest that L-type Ca(2+) channels may play a pivotal role for magnesium-induced relaxation.