Prediction of Acquired Taxane Resistance Using a Personalized Pathway-Based Machine Learning Method / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to develop and validate an individualized prediction model for automated detection of acquired taxane resistance (ATR). MATERIALS AND METHODS: Penalized regression, combinedwith an individualized pathway score algorithm,was applied to construct a predictive model using publically available genomic cohorts of ATR and intrinsic taxane resistance (ITR). To develop a model with enhanced generalizability, we merged multiple ATR studies then updated the learning parameter via robust cross-study validation. RESULTS: For internal cross-study validation, the ATR model produced a perfect performance with an overall area under the receiver operating curve (AUROC) of 1.000 with an area under the precision-recall curve (AUPRC) of 1.000, a Brier score of 0.007, a sensitivity and a specificity of 100%. The model showed an excellent performance on two independent blind ATR cohorts (overall AUROC of 0.940, AUPRC of 0.940, a Brier score of 0.127). When we applied our algorithm to two large-scale pharmacogenomic resources for ITR, the Cancer Genome Project (CGP) and the Cancer Cell Line Encyclopedia (CCLE), an overall ITR cross-study AUROC was 0.70, which is a far better accuracy than an almost random level reported by previous studies. Furthermore, this model had a high transferability on blind ATR cohorts with an AUROC of 0.69, suggesting that general predictive features may be at work across both ITR and ATR. CONCLUSION: We successfully constructed a multi-study–derived personalized prediction model for ATR with excellent accuracy, generalizability, and transferability.

Long-term Activation of c-Jun N-terminal Kinase through Receptor Interacting Protein is Associated with DNA Damage-induced Cell Death

Activation of c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is an important cellular response that modulates the outcome of the cells which are exposed to the tumor necrosis factor (TNF) or the genotoxic stress including DNA damaging agents. Although it is known that JNK is activated in response to genotoxic stress, neither the pathways to transduce signals to activate JNK nor the primary sensors of the cells that trigger the stress response have been identified. Here, we report that the receptor interacting protein (RIP), a key adaptor protein of TNF signaling, was required to activate JNK in the cells treated with certain DNA damaging agents such as adriamycin (Adr) and 1-beta-D-arabinofuranosylcytosine (Ara-C) that cause slow and sustained activation, but it was not required when treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and short wavelength UV, which causes quick and transient activation. Our findings revealed that this sustained JNK activation was not mediated by the TNF (tumor necrosis factor) receptor signaling, but it required a functional ATM (ataxia telangiectasia) activity. In addition, JNK inhibitor SP-600125 significantly blocked the Adr-induced cell death, but it did not affect the cell death induced by MNNG. These findings suggest that the sustained activation of JNK mediated by RIP plays an important role in the DNA damage-induced cell death, and that the duration of JNK activation relays a different stress response to determine the cell fate.

Prevention of TNF-induced necrotic cell death by rottlerin through a Nox1 NADPH oxidase

Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2") through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2(-) production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.

Ventriculostomy-Associated Infection : Analysis of Risk Factors and the Venue of External Ventricular Drainage / 대한뇌혈관외과학회지

OBJECTIVE: The purpose of this study is to evaluate the risk factors for ventriculostomy-associated infections (VAI) and to examine the differences among VAI according to the venue of catheter placement in our institute. Materials and METHODS: During a four-year period, 114 patients of the neurosurgical intensive care unit (NICU) who received an external ventricular drainage (EVD), were retrospectively studied. The use of prophylactic systemic antibiotics was not included in the evaluation of the risk factors for VAI, because this was applied to all patients in our trial. RESULTS: One hundred sixty-five catheters were placed, in 114 patients, among whom 7.9% developed ventriculitis. The risk of VAI was not significantly associated with age, intial Glasgow coma scale (GCS) score, indication for the catheter, craniotomy, duration of catheter, DM, hypertension and repeated catheter insertion. Furthermore, EVD catheterization in non-operating places was not associated with a trend toward higher VAI as well. CONCLUSION: Risk factors for an increased incidence of VAI were not observed in our trials. In our study, the risk of VAI was not associated with the venue of catheter placement. These findings suggest that EVD catheter insertion in non-operating places may be a safe procedure without the risk of VAI.

Transcriptional Regulation of the Estrogen Receptor alpha Gene by Testosterone in Cultures of Primary Rat Sertoli Cells / 대한내분비학회지

BACKGROUND: We wanted to identify the presence of the estrogen receptor (ER) alpha in Sertoli cells and gain insight on the regulation of the ER alpha gene expression by testosterone in Sertoli cells. The transcriptional regulation of the ER alpha gene was investigated in primary Sertoli cell cultures by in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). METHODS: Primary Sertoli cell culture was performed. The expression levels of ER alpha and ER beta mRNA in Sertoli cells were detected by Northern blot, RT-PCR, immunocytochemistry and in situ hybridization. RESULTS: The ovary, testis and epididymis showed a moderate to high expression of ER alpha while the prostate, ovary and LNCap cells showed the ER beta expression. ER alpha mRNA and protein were detected in the germ cells and Sertoli cells by in situ hybridization and immunocytochemistry. The level of ER alpha mRNA was gradually decreased in a time-dependent manner after testosterone treatment, and the changes of ER alpha mRNA were dependent on the concentration of testosterone. Androgen binding protein and testosterone-repressive prostate message-2 (TRPM-2) mRNA were reduced at 24 hour by estradiol, while the transferrin mRNA was not affected. ER alpha mRNA was strongly detectable in the testes of 7 days-old-rats, but it was gradually decreased from 14 to 21 days of age. The primary Sertoli cells also showed the same pattern. The ER alpha gene expression was also regulated by testosterone in the Sertoli cells prepared from the 14- and 21-day old rats. CONCLUSIONS: These results suggest that ER alpha is transcriptionally regulated by testosterone and it may play some role in the Sertoli cells.

Mechanism of Castration-induced Apoptosis of Ventral Prostate in Rat / 대한내분비학회지

BACKGROUNDS: Castration-induced androgen deprivation triggers a sequence of events, which activates apoptotic cell death of the androgen-dependent epithelial cells within the rat ventral prostate. To investigate the mechanism of castration-dependent apoptosis in the rat ventral prostate, the regulation of apoptosis-related genes was been investigated. METHODS: Azaline B was subcutaneously injected into Sprague-Dawley rat. The Fas receptor (Fas), Fas ligand (FasL) and bcl-2 mRNA, as well as the protein levels were detected by RT-PCR and Western blot analyses. Azaline B-dependent apoptosis was determined using TUNEL and a DNA fragmentation assay. The transacting factor of the FasL promoter was identified by DNA footprinting and a DNA mobility shift assay. RESULTS: The rat prostate was regressed after castration, with and the involuted ventral prostate regenerated by testosterone pretreatment, but not by that with FSH. Apoptosis of the ventral prostate was detected, after castration, using toluidine blue staining, a TUNEL assay and an apoptotic DNA fragmentation assay. The levels of Fas, FasL mRNA and protein were increased after castration. In the DNase I footprinting assay, using the FasL promoter and a nuclear extract prepared from a control prostate, at least two sites were protected: the SP-1 binding site at -283 bp and the prostate-unidentified factor(P-UF) binding site at -247 bp. The SP-1 binding activity vanished in the nuclear extract prepared from castrated rats. In the DNA mobility shift assay, the SP-1 binding activity was slightly decreased after castration. Both the Bcl-2 mRNA and Bcl-2 protein were downregulated after castration. CONCLUSION: These results suggest that the Fas/FasL system and Bcl-2 may be important to castrationdependent apoptosis in the rat ventral prostate, with SP-1 related to the castration-dependent regulation of the FasL gene

Mechanism of Castration-induced Apoptosis of Ventral Prostate in Rat / 대한내분비학회지

BACKGROUNDS: Castration-induced androgen deprivation triggers a sequence of events, which activates apoptotic cell death of the androgen-dependent epithelial cells within the rat ventral prostate. To investigate the mechanism of castration-dependent apoptosis in the rat ventral prostate, the regulation of apoptosis-related genes was been investigated. METHODS: Azaline B was subcutaneously injected into Sprague-Dawley rat. The Fas receptor (Fas), Fas ligand (FasL) and bcl-2 mRNA, as well as the protein levels were detected by RT-PCR and Western blot analyses. Azaline B-dependent apoptosis was determined using TUNEL and a DNA fragmentation assay. The transacting factor of the FasL promoter was identified by DNA footprinting and a DNA mobility shift assay. RESULTS: The rat prostate was regressed after castration, with and the involuted ventral prostate regenerated by testosterone pretreatment, but not by that with FSH. Apoptosis of the ventral prostate was detected, after castration, using toluidine blue staining, a TUNEL assay and an apoptotic DNA fragmentation assay. The levels of Fas, FasL mRNA and protein were increased after castration. In the DNase I footprinting assay, using the FasL promoter and a nuclear extract prepared from a control prostate, at least two sites were protected: the SP-1 binding site at -283 bp and the prostate-unidentified factor(P-UF) binding site at -247 bp. The SP-1 binding activity vanished in the nuclear extract prepared from castrated rats. In the DNA mobility shift assay, the SP-1 binding activity was slightly decreased after castration. Both the Bcl-2 mRNA and Bcl-2 protein were downregulated after castration. CONCLUSION: These results suggest that the Fas/FasL system and Bcl-2 may be important to castrationdependent apoptosis in the rat ventral prostate, with SP-1 related to the castration-dependent regulation of the FasL gene

Mechanism of Azaline B-induced Apoptosis in Rat Testis / 대한비뇨기과학회지

PURPOSE: To identify the mechanism of azaline B-dependent apoptosis, the regulation of Fas and FasL genes has been investigated. MATERIALS AND METHODS: Azaline B was subcutaneously injected into Sprague-Dawley rats. The levels of Fas receptor (Fas) and Fas ligand (FasL) were detected by reverse transcription-polymerase chain reaction (RT- PCR). Azaline B-dependent apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL) and DNA fragmentation assay. Transacting factor of FasL promoter was identified by DNase I footprinting and DNA mobility shift assay. RESULTS: The azaline B-treated testis (250microgram/kg body wt/day) had decreased to 70+/-2.5% and 38+/-1.8% of the normal testis weight at 3 and 5 days after the injection, respectively, but the weights of the testis were not changed after pretreatment of follicle-stimulating hormone (FSH) and testosterone. Apoptosis of the testis was detected by DNA fragmentation assay and TUNEL assay after the azaline B treatment. The levels of Fas and FasL mRNA were increased by the treatment of azaline B in both time- and dose-dependent manners. In DNase I footprinting assay with FasL promoter, the nuclear factor prepared from control was bound with at least four sites: SP-1 binding site at 283, NF-kappa B binding site at 219, TATA at 132 and the gamma-interferon response element (gamma-IRE) at 78. gamma-IRE was completely protected by the nuclear extract prepared from azaline B-treated rat testis. In DNA mobility shift assay, the binding activity of gamma-IRE binding protein was increased after azaline B treatment. CONCLUSIONS: These results suggest that Fas-FasL system may be important to azaline B-dependent apoptosis in rat testis and that gamma-IRE binding protein is related to the azaline B-dependent regulation of FasL gene.

Enhancement of ATP-induced Currents by Phospholipase D1 Overexpressed in PC12 Cells

Using phospholipase D1 (PLD1) -overexpressing PC12 (PLD1-PC12) cells, the regulatory roles of PLD1 on ATP-induced currents were investigated. In control and PLD1-PC12 cells, ATP increased PLD activity in an external Ca2+ dependent manner. PLD activity stimulated by ATP was substantially larger in PLD1-PC12 cells than in control cells. In whole-cell voltage-clamp mode, ATP induced transient inward and outward currents. The outward currents inhibited by TEA or charybdotoxin were significantly larger in PLD1-PC12 cells than in control cells. The inward currents known as Ca2+ permeable nonselective cation currents were also larger in PLD1-PC12 cells than in control cells. However, the difference between the two groups of cells disappeared in Ca2+ -free external solution, where ATP did not activate PLD. Finally, ATP-induced 45Ca uptakes were also larger in PLD1-PC12 cells than in control cells. These results suggest that PLD enhances ATP-induced Ca2+ influx via Ca2+ permeable nonselective cation channels and increases subsequent Ca2+ -activated K+ currents in PC12 cells.

Activation of epidermal growth factor receptor is responsible for pervanadate-induced phospholipase D activation

Pervanadate, a complex of vanadate and H2O2, has an insulin mimetic effect, and acts as an inhibitor of protein tyrosine phosphatase. Pervanadate-induced phospholipase D (PLD) activation is known to be dependent on the tyrosine phosphorylation of cellular proteins and protein kinase C (PKC) activation, and yet underlying molecular mechanisms are not clearly understood. Here, we investigated the signaling pathway of pervanadate-induced PLD activation in Rat2 fibroblasts. Pervanadate increased PLD activity in dose- and time- dependent manner. Protein tyrosine kinase inhibitor, genistein, blocked PLD activation. Interestingly, AG-1478, a specific inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR) blocked not only the PLD activation completely but also phosphorylation of p38 mitogen- activated protein kinase (MAPK). However, AG-1295, an inhibitor specific for the tyrosine kinase activity of pletlet drived growth factor receptor (PDGFR) did not show any effect on the PLD activation by pervanadate. We further found that pervanadate increased phosphorylation levels of p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK). SB203580, a p38 MAPK inhibitor, blocked the PLD activation completely. However, the inhibitions of ERK by the treatment of PD98059 or of JNK by the overexpression of JNK interacting peptide JBD did not show any effect on pervanadate-induced PLD activation. Inhibition or down-regulation of PKC did not alter the pervanadate-induced PLD activation in Rat2 cells. Thus, these results suggest that pervanadate-induced PLD activation is coupled to the transactivation of EGFR by pervanadate resulting in the activation of p38 MAP kinase.

Meningeal Chloromain in Acute Lymphoblastic Leukemia

Isolated chloromas(granulocytic sarcomas) are rare tumors. Chloromas are masses composed of immature granulocytic cells. Granulocytic sarcoma occurs primarily in patients with acute myelogenous leukemia as well as in patients with other myeloproliferative disorders, but rarely in patients with acute lymphoblastic leukemia(ALL). We now describe one patient affected by ALL with isolated granulocytic sarcoma as initial CNS relapses. These unusual clinical manifestation and radiological finding in acute lymphoblastic leukemia should be considered as recurrence of leukemia. Early detection and antileukemic treatment of granulocytic sarcoma are necessarily important for favorable prognosis.

Accuracy of References in Journal of the Korean Pediatric Society and Journals of the Korean Pediatric Subspecialty Societies and Citation Pattern Analysis

PURPOSE: We tried to check the accuracy of references in the Journal of the Korean Pediatric Society and Journals of the Korean Pediatric Subspecialty Societies. We also wanted to know the citation patterns of authors by analyzing the frequency of cited materials. METHODS: Three journals were randomly selected from the 2000 issues of Journal of the Korean Pediatric Society and nine journals were selected mainly from the second half of 2000 issues of each Journal of the Korean Pediatric Subspecialty Societies for the study. Then the accuracy of references was checked with Medline. Journals before 1964, books, and journals which were not written in English were used only in the citation pattern analysis. RESULTS: Author errors were the most common(21.3%) among the reference elements. The next was title errors, followed by page errors, journal errors, volume errors and year errors. Total average error rate was 34.7% and we were unable to find journals in 89 cases(2.2%). The journal of the Korean Society of Neonatology had the lowest error rate(17.4%) and the journal of the Korean Pediatric Cardiology Society had the highest error rate(53.2%). The reference journals which were published and quoted in the most recent three years were only 612 cases(15%). Foreign journals were selected as reference(78.4%) more than domestic journals; The Journal of the Korean Pediatric Society was the most frequently cited reference(43.3%) among domestic journals. CONCLUSION: Authors are ultimately responsible for the accuracy of references and they should check the reference list with responsibility. Hopefully, authors also will have to use more domestic journals and recent journals.

A Sedimentation Level in Pituitary Adenoma on Magnetic Resonance Imaging

We present a rare case of a pituitary adenoma revealing a sedimentation level on MRI, which has not been previously documented. This 55-year-old woman was referred with the diagnosis of craniopharyngioma. She presented with four-month history of progressive headache and visual dimness. Neurological examination revealed a bitemporal hemianopsia and decreased visual acuity. Laboratory data including endocrine examination were unremarkable. An additional three-dimensional MRI was taken for further evaluation, and demonstrated a sedimentation level within the tumor. The patient underwent transcranial removal of the tumor. About 12cc of dark-red blood was aspirated from the tumor. Histological examination revealed a pituitary adenoma with hemorrhage. Postoperatively, the patient showed gradual improvement of visual function. Considering that the pituitary adenoma is one of more common tumors that cause tumoral bleeding, a cystic sellar tumor that has a sedimentation level should be sought first for a pituitary adenoma rather than a craniopharyngioma. This may have an important impact when deciding surgical approach.

Clinical and Electrographic Characteristics of Intractable Childhood Epilepsy with Complete Seizure Remission Over 6 Months After Ketogenic Diet / 대한소아신경학회지

PURPOSE: The efficacy of ketogenic diet in intractable childhood epilepsy has been reported in Korea. The aim of this retrospective study is to elicit the clinical and electrophysiological characteristics of intractable chilhood epilepsy, who can be successfully treated by ketogenic diet and to determine the favorable outcome group for ketogenic diet in intractable chilhood epilepsy. METHODS: We investigated clinical seizure type, epilepsy classification, underlying etiologies, clinical characteristics, EEG findings, response to treatments, and prognosis were studied in 41 patients with complete seizure remission over 6 months after ketogenic diet as compared with unsuccessful group among 96 patients of trial from July 1995 to October 1999 at the pediatric department of and epilepsy center at Sang-gye Paik Hospital, Inje University. RESULTS: 1) Complete seizure remission over 6 months were obtained in 15 patients of infantile spasms (IS), 6 cases of Lennox-Gastaut syndrome (LGS), 4 cases of periodic spasms, 3 cases of severe myoclonic epilepsy in infancy (SMEI), 1 case of Landau-Kleffner syndrome, 8 cases of other type of partial epilepsies. 2) Ketogenic diet was more effective in infantile spasms and periodic spasms but least effective in Lennox-Gastaut syndome. 3) In same types of epilepsies, ketogenic diet was more effective in patients with less frequent seizures, less severe EEG findings and earlier controlling seizures. CONCLUSIONS: Ketogenic diet was most effective in infantile spasms, patients with less frequent seizure in same type of epilepsy, less severe EEG findings in same seizure type, and patients who seizures stopped sooner after administration of ketogenic diet.

Five Cases of Prader-Willi or Angelman Syndrome Diagnosed by FISH in Neonate and Infancy

The Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct syndromes with a shared cytogenetic deletion of chromosome 15q11q13 in most patients. Currently the diagnosis of PWS/AS is clinically suspected and can be confirmed by genetic laboratory tests. However, their diagnosis remains difficult in neonates and early infants because many features of the syndromes change with age and the typical features do not present in this early period. Recently, we experienced 5 cases of PWS/AS, confirmed by fluorescence in situ hybridization (FISH) study in neonates and infants admitted to neonatal intensive care unit due to hypotonia and feeding problems. We believe that these syndromes are far more common than previously thought, and report thes 5 cases to emphasize the importance of early diagnosis in order to provide appropriate counselling for the parents. We recommend molecular genetic studies of PWS/ AS in floppy infants who have feeding problems during the neonate stage and infancy.

Five Cases of Prader-Willi or Angelman Syndrome Diagnosed by FISH in Neonate and Infancy

The Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct syndromes with a shared cytogenetic deletion of chromosome 15q11q13 in most patients. Currently the diagnosis of PWS/AS is clinically suspected and can be confirmed by genetic laboratory tests. However, their diagnosis remains difficult in neonates and early infants because many features of the syndromes change with age and the typical features do not present in this early period. Recently, we experienced 5 cases of PWS/AS, confirmed by fluorescence in situ hybridization (FISH) study in neonates and infants admitted to neonatal intensive care unit due to hypotonia and feeding problems. We believe that these syndromes are far more common than previously thought, and report thes 5 cases to emphasize the importance of early diagnosis in order to provide appropriate counselling for the parents. We recommend molecular genetic studies of PWS/ AS in floppy infants who have feeding problems during the neonate stage and infancy.

A Retrospective Analysis of MRI-verified 29 Cases of Transverse Myelitis

No abstract available.

The Effect of Pentoxifylline on IL-1beta and TNF-alpha mRNA Gene Expression in Hypoxic-Ischemic Brain Injury of Immature Rat / 대한소아신경학회지

PURPOSE: Interleukin-1beta(IL-1beta) and Tumor necrosis factor-alpha(TNF-alpha) are multifunctional cytokines that may play important roles both in the normal development of central nervous system and in the response of brain to diverse forms of injury. IL-1beta and TNF-alpha have potent proinflammatory action and the potential to modulate cell growth. Cerebral hypoxia-ischemia selectively stimulates IL-1beta and TNF-alpha gene expression in brain regions susceptible to irreversible injury in perinatal rats. Pentoxifylline, a cAMP phosphodiesterase inhibitor, attenuates hypoxic-ischemic brain injury in immature rats and inhibits TNF-alpha expression at the transcription level. We hypothesize that pentoxifylline would attenuate the expression of IL-1beta and TNF-alpha mRNA gene expression on hypoxic-ischemic brain injury in immature rats. METHODS: To elicit focal hypoxic-ischemic brain injury, 7-d-old(P7) rats underwent right carotid artery ligation, followed by 3 hr of hypoxia(fractional concentration of inspired O2=0.08). In 3 rats, pentoxifylline(40mg/kg) was injected into the intraperitoneal cavity immediately before and after hypoxia. The other 4 rats were given PBS solutions. IL-1beta and TNF-alpha mRNA content were measured by reverse transcription followed by polymerase chain reaction amplification(RT-PCR) in the samples prepared from the lesioned and contralateral hemispheres killed 4 hr post-hypoxia. cDNA were amplified with primers specific for IL-1beta and TNF-alpha. and also amplified with GAPDH primers which served as an internal control. RESULTS: In control group, hypoxia-ischemia induced IL-1beta and TNF-alpha mRNA expression from the lesioned hemisphere in immature rat brain. In pentoxifylline treated group, IL-1beta and TNF-alpha mRNA expression were attenuated at 4 hr post hypoxia- ischemia. CONCLUSION: Preteatment with pentoxifylline decreased incidence and severity of hypoxic-ischemic injury in immature rat brain. Pentoxifylline attenuated the expression of IL-1beta and TNF-alpha gene on hypoxic-ischemic injury in immature rat brain. IL-1beta and TNF-alpha may play important roles in the response of the developing brain to acute hypoxic-ischemic injury.

A Case of Listeria Meningoencephalitis in a Healthy Child

Listeriosis in a healthy child is extremely rare. A previously healthy 9-year-old male was admitted with pyrexia, headache and lethargy. The CSF cultures, taken on admission and on the 5th day, showed growth of Listeria monocytogenes. L. monocytogenes was identified by various methods, including polymerase chain reaction(PCR). Serologically, it showed type 1/2a. However, blood cultures, which were taken on the same days, revealed no growth of L. monocytogenes. Ceftriaxone and amikacin had no effect on the progress of the disease. The combination of ampicillin plus gentamicin, which is regarded as the treatment of choice for L. monocytogenes infection, had an effect in this case. Patient showed severe neurological symptoms and signs, such as diplopia, esotropia, nystagmus, ptosis and other meningeal signs during the hospital days, even though all such symptoms and signs were improved at discharge. We report the case with brief review of related literatures.

Neuroprotective Effects by Magnesium Sulfate Pretreatment against Hypoxia-Ischemia in the Newborn Rat: Preliminary report / 대한소아신경학회지

PURPOSE AND BACKGROUND: Recently several clinical studies suggested that maternal treatment with magnesium sulfate had protective effects against cerebral palsy in premature infants. But previous studies with differing perinatal animal models resulted in inconclusive results with regard to magnesium neuroprotection. Our purpose was to study the neuroprotective effect of magnesium sulfate and optimal dosage on hypoxicischemic brain damage in the newborn rat. METHOD: Seven-day-old rats(n=68) underwent right carotid ligation, followed by 3 hours of hypoxia(8% oxygen in 92% nitrogen). Rats received magnesium sulfate immediately before and again after hypoxia(two doses, 150mg-600mg/kg/dose, n=39), or saline solution(n=29). Severity of injury was assessed 5 days later, by visual evaluation of ipsilateral hemisphere infarction and by measurement of bilateral hemispheric cross sectional areas. RESULTS: Magnesium sulfate pre-treatment reduced the incidence of liquefactive cerebral infarction and atrophy from 80.8% in controls to 22.2% with magnesium sulfate(450 mg/kg/dose, P<0.05). Quantitation of hemispheric areas confirmed these findings. Percent protection based on inter-hemisphere area differences by pre-treatment with magnesium sulfate 450mg/kg/dose ranged from 71.1%(hippocampus) to 90.8%(striatum). However higher dose of magnesium(600mg/kg/dose) did not attenuate hypoxic-ischemic brain injury in the newborn rat but increased mortality. CONCLUSION: Pretreatment of magnesium sulfate has neuroprotective effects against hypoxia-ischemia in the newborn rat and adequate dose of magnesium sufate is important to protect the brain. Magnesium pretreatment may be an effective strategy to decrease the severity of neonatal hypoxic-ischemic brain injury in the adequate dose.