The Effects of Preoperative 18F-FDG PET/CT in Breast Cancer Patients in Comparison to the Conventional Imaging Study / 한국유방암학회지

PURPOSE: There have been recent studies of the 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) in the staging, detection, and follow-up of the breast cancer occurrence and recurrence. There was controversy concerning the use of 18F-FDG PET/CT for staging primary breast cancer. In this study, we investigated the potential effects of 18F-FDG PET/CT in the initial assessment of patients with primary breast cancer. METHODS: From January 2008 to December 2009, 154 consecutive biopsy-proven invasive breast cancer patients were enrolled in this study. Patients underwent conventional imaging studies including mammography, breast ultrasonography (USG), and magnetic resonance imaging for local assessment, and plain chest X-ray, liver USG, and bone scan to rule out distant metastasis. All 154 patients underwent 18F-FDG PET/CT in the initial assessment. RESULTS: 18F-FDG PET/CT did not detect primary breast lesions in 16 patients with a sensitivity of 89.6% and detected only 5 multiple lesions (12.5%) out of 40 cases. Histologically confirmed axillary lymph node (LN) metastases were in 51 patients, and the sensitivity and specificity of 18F-FDG PET/CT to detect metastatic axilla were 37.3% and 95.8%, respectively; whereas the corresponding estimates of USG were 41.2% and 93.7%, respectively. Eleven extra-axillary LN metastases were found in eight patients, and seven lesions were detected by 18F-FDG PET/CT only. The sensitivity and specificity of 18F-FDG PET/CT in detecting distant metastasis were 100% and 96.4%, respectively; whereas the sensitivity and specificity of the conventional imaging were 61.5% and 99.2%, respectively. CONCLUSION: 18F-FDG PET/CT cannot be recommended as a primary diagnostic procedure in breast cancer, but it has the potential to be used as an additional imaging tool for the detection of axillary metastasis, distant metastasis, and extra-axillary LN metastasis. 18F-FDG PET/CT cannot solely replace the conventional diagnostic procedure in primary breast cancer. The best approach may be the combination of different imaging modalities.

Usefulness of Urinary Cotinine Test to Discriminate between Smokers and Nonsmokers in Korean Adolescents / 대한진단검사의학회지

BACKGROUND: Recently we have demonstrated that urinary cotinine test by an enzyme immunoassay is valid to discriminate smoking status among adults. This study was conducted for the same purpose among Korean high school students. METHODS: Questionnaire on smoking and urinary cotinine tests were performed for 1, 267 high school students. Cotinine concentrations in urine were measured by Cotinine Enzyme Immunoassay (Diag-nostic Reagents Inc., CA, USA) on 502X Multiple Chemistry Unit (A&T Co., Tokyo, Japan). RESULTS: The questionnaire was responded by 1, 227 of the 1, 267 students (96.8%); 6 male (0.8%) and 34 female students (5.9%) did not respond. Among the responders, 13.4% (92/685) of male students and 3.0% (16/542) of female students answered as smokers. By using 6 ng/mL as a cutoff, the sensitivity and specificity of the urinary cotinine test were 79.6% (86/108) and 91.4% (1023/1119), respectively. According to the results of urinary cotinine, 96 additional students were presumed as smokers. Of 85 abstainers and 40 non-responders, 41 (32.8%) tested positive for urinary cotinine. CONCLUSIONS: Unlike in a previous study with adults, the urinary cotinine test is shown not to be able to replace the self-reported questionnaire due to the lack of sensitivity for young adolescents. But the urinary continine test is valid to discriminate smokers among purported nonsmokers, espe-cially among non-responders and those who claimed abstinence.

Usefulness of Urinary Cotinine Test to Distinguish Smokers from Nonsmokers / 대한진단검사의학회지

BACKGROUND: Self-reports of smoking may not always be reliable. A number of biochemical markers have been used to validate claims of nonsmoking, among which the most widely used specific marker has been the nicotine metabolite cotinine. This study was conducted to evaluate the performance of the enzyme immunoassay (EIA) for urinary cotinine to determine smoking status. METHODS: Questionnaires on smoking and urinary cotinine measures were studied in 287 persons. Urinary cotinine concentration was measured by the Cotinine Enzyme Immunoassay (Diagnostic Reagents, Inc., CA, USA) on the 502X Multiple Chemistry Unit (A &T Co., Tokyo, Japan). RESULTS: Using cutoffs of 0 ng/mL, 20 ng/mL or 100 ng/mL for urinary cotinine measured by the EIA method, the sensitivities were 100%, 97.6%, and 94.4% respectively and the specificities were 97.5%, 98.8%, and 100% respectively. By retrograde telephone questionnaires, 3.8% of the subjects were confirmed as deceiving their smoking status. Active smokers of or =10 cigarettes (1, 052 ng/mL). CONCLUSIONS: Urinary cotinine measured by EIA is a rapid, lab-based test that can reliably determine smoking status. Considering the various purpose of the test, different cut-offs should be used.

Analysis of Effectiveness of the Maximum Surgical Blood Order Schedule / 대한수혈학회지

BACKGROUND: The maximum surgical blood order schedule (MSBOS) is a viable option for reducing unnecessary crossmatching and achieving significant cost savings in the blood bank. In this study, we showed the process establishing MSBOS and through a prospective study, we evaluated the efficacy of MSBOS. METHODS: We organized task force team for transfusion management improvement composed of a director of the blood bank, surgeons and anesthesiologists in the Committee for Quality Improvement (CQI) of Asan Medical Center. In this team, we established MSBOS for most elective surgeries through the review of the previous transfusion and crossmatching data. We introduced MSBOS in April 1998 and prospectively analyzed surgeon's acceptance rate of MSBOS, crossmatch-to-transfusion ratio (C/T ratio), blood wastage rate, and cost savings. RESULTS: During the first 19 months after introducing MSBOS at our hospital, there was gradual increase in the surgeon's compliance rate of MSBOS from 30% to 94.0% through continuous education. The C/T ratio was changed from 3.5 to 1.6 and blood wastage rate was decreased from 4.0% to 1.9%. And also we could save more than 38,400,000 won through not performing the unnecessary crossmatches of 7,680 cases per year. CONCLUSION: Introduction of MSBOS can have a significant impact in reducing C/T ratio, blood wastage rate, and unnecessary crossmatches for the unused blood units. For successful application of MSBOS, cooperation with surgeons and anesthesiologists and continuous education is essential.

Usefulness of IMI and HPC of Sysmex SE-9000, and IRF and HFR of Sysmex R-3000 to Refine Apheresis Timing of Peripheral Blood Stem Cell Harvest / 대한혈액학회지

BACKGROUND: The Sysmex SE-9000 and R- 3000 automated cell counters provide estimates of immature cells referred to as immature myeloid information (IMI), hematopoietic progenitor cells (HPC), immature reticulocyte fraction (IRF) as high and medium fluorescent reticulocytes, and high fluorescence ratio (HFR) as high fluorescent reticulocytes. The aim of this study was to evaluate whether these parameters were useful to refine apheresis timing of peripheral blood stem cell (PBSC) harvest. METHOD: For 140 peripheral blood harvest procedures of 26 patients, pre-harvest peripheral blood (PB) WBC, mononuclear cells (MNC), IMI, HPC, CD34-positive cells, reticulocyte (%, number), IRF and HFR were tested and compared with harvested CD34-positive cell content. RESULTS: Correlation coefficients between pre-harvest WBC, MNC, IMI, HPC, CD34-positive cells, reticulocyte %, reticulocyte number, IRF and HFR of PB and harvested CD34-positive cell content were 0.15, 0.06, 0.60, 0.78, 0.77, 0.004, 0.06, 0.28 and 0.40. Applying the criteria IMI 300X10degrees/L, HPC 5X10degrees/L and CD34-positive cells 5X10derees/L of PB on the first day of 30 cycles of harvests, positive predictive value to predict the mean CD34+ cell count over 0.5X106/kg per one leukapheresis and negative predictive value to predict the mean CD34+ cell count less than 0.5X10derees/kg per one leukapheresis were 73.3%/93.3%, 57.8%/90.9% and 78.6%/ 93.7% respectively. CONCLUSION: Pre-harvest PB IMI and HPC of Sysmex SE-9000 are comparable with PB CD34- positive cells in terms of correlation with harvested CD34-positive cell content. For PB IMI and HPC are simple, inexpensive and rapid to get results, PB IMI and HPC are useful to refine apheresis timing of PBSC harvests and to screen poor-mobilizers.

Total Antioxidant Status, Lipid Peroxidation and Autoantibody to Oxidized Low Density Lipoprotein in Diabetes Mellitus / 대한임상병리학회지

BACKGROUND: Oxidative stress, lipid peroxidation and immune response to oxidized low density lipoprotein(oxLDL) are important events in the progression of atherosclerosis in diabetes mellitus(DM). Though, many clinical studies used man-made reagents that the reproducibility of the tests was not reliable and showed controversial results in some aspects. We performed above three tests in DM patients by the commercial kits and compared our results with previous results. METHODS: Total 67 DM patients and sex- and age-matched healthy persons were tested about total antioxidant status(TAS), lipid peroxidation(LPO) and autoantibody to oxLDL(anti-oxLDL) by Total Antioxidant Status kit(RANDOX Labs., Crumlin, UK), BIOXYTECH LPO-586 kit(OXIS International Inc., Portland, OR, USA) and Ox-LDL IgG ELISA kit(BIODESIGN International, Kennenbunk, ME, USA) each. RESULTS: The intra-run and between-run coefficients of variation of TAS and LPO were 2.6/2.7% and 13.4/15.6% respectively. The intra-run coefficient of variation of anti-oxLDL was 1.8 to 6.9%. DM patients showed decreased TAS(1.31+/-0.15 mmol/L) when compared with normal controls(1.38+/-0.09 mmol/L, P <0.01). TAS was inversely correlated with HbA1c(r=-0.38, P <0.01). LPO and anti-oxLDL in DM patients did not differ significantly from normal controls. CONCLUSIONS: By commercial kits, we could get reproducible results of TAS and anti-oxLDL, but not LPO test. The results of TAS and HbA1c among the DM patients and normal controls suggested that poor glycemic control might be associated with decrease of TAS. We could not find significant difference in the results of LPO and anti-oxLDL between two groups.

Evaluation of MicroScan Neg Combo Panel type 21 to Detect ESBL / 대한임상미생물학회지

BACKGROUND: Escherichia coli and Klebsiella pneumoniae resistant to 3rd generation cephalosporin have been reported with increasing frequency in tertiary-care hospital in Korea. MicroScan Neg Combo Panel Type 21 (Type 21) contains a 1 microgram/mL cepfodoxime (POD) in addition to other screen wells containing ceftazidime, cefotaxime, ceftriaxone, and aztreonam, which are designed for detecting extended-spectrum beta-lactamase (ESBL)-producing E. coli and Klebsiella species. We evaluated the Type 21 panel for its ability to detect ESBL. METHODS: From November to December in 1998, 496 E. coli and 326 K. pneumoniae strains isolated from clinical specimens were tested with Type 21 panel The isolates flagged as ESBL producers by the panel were confirmed by the double disk synergy test (DDS). To evaluate the specificity of POD, n-lactamases of 54 E, coli and 20 K. pneumoniae strains that were flagged by, POD only from January to May 1999 were analyzed by isoelectric focusing(IEF). RESULTS: 75/496(15%) E. coli and 68/326(21%) K. pneumoniae were flagged as ESBL producers by Type 21 panel. Of those, 94 isolates including 38/75 (51%) of E. coli and 56/68 (82%) of K. pneumoniae were positive for DDS. Among the 94 ESBL producers, all were detected by POD, 84% by cefotaxime, 85% by ceftazidime, 84% by ceftriaxone, and 86% by aztreonam. The 74 strains that were flagged as ESBL producers by POD screen well only were mostly DDS-negative, cefoxitin- resistant and showed beta-lactamases with pls of 5.4 and 7.6 or no band, which could be interpreted as the presence of TEM-1 or SHV-1 type beta-lactamases and/or basal AmpC beta-lactamases, not ESBL. CONCLUSION: MicroScan Neg Combo Panel Type 21 was able to detect a greater number of ESBL producers by inclusion of POD in its screening well. However, the specificity of POD was compromised by flagging a significant number of DDS negative strains. We conclude that the isolates with reduced susceptibility to 3rd generation cephalosporins as well as POD can be reported as ESBL-producers and those resistant to POD only should be confirmed by DDS.

Human genomic DNA isolation and chromosomal localization of fetal brain cDNA (FB174) / 대한해부학회지

Eventhough surmountable amounts of genes are being cloned and a number of methods are being developed by human genome project, it's not easy to predict possible functions of genes and determine the chromosomal locations of genes. In this experiment, cDNA pool was made from 18 weeks old human fetal brain and analyzed the sequences. FB174 clone was chosen, in situ hybridization histochemistry was performed on developing and adult rat tissue section to observe the tissue specificity and developmental expression of this gene. To observe the chromosomal location of FB174 clone, the genomic DNA from human genomic library was isolated and fluorescence in situ hybridization was carried out. By sequencing and sequence search with GenBank data it was revealed that cloned FB174 cDNA was quite similar to translationally controlled tumor protein which is known to locate to human chromosome 13q14. The expression of FB174 mRNA was not detected in rat tissue sections by in situ hybridization histochemistry. Fluorescence in situ hybridization using biotin labeled FB174 probe resulted in specific labeling of human chromosome 7q22. These results and high sequence homology of FB174 to known translationally controlled tumor protein suggest that FB174 clone may be a new translationally controlled tumor protein-related gene.

Expression of protein kinase C-gamma mRNA on the spinal cord in a rat model of neuropathic pain / 대한해부학회지

Partial peripheral nerve injury occasionally results in neuropathic pain, including spontaneous burning pain and increased sensitivity to sensory stimuli such as hyperalgesia and allodynia. The pathophysiological mechanisms underlying this disease are poorly understood and the available treatments unsatisfactory. Presently, the neuropathic pain is believed to result from an increase in the excitability of the dorsal horn neurons (central sensitization), which is induced by abnormal signals from injured afferents. PKC-gamma is known to play a pivotal role in central sensitization following peripheral nerve injury. In the present study, we examine the expression of PKC-gamma mRNA of the spinal dorsal horn after neuropathic injury. There was no significant difference of PKC-gamma mRNA between lesion and control sides. These results suggest that PKC-gamma mRNA is not a key factor for the generation of neuropathic pain.

The effect of convulsive treatments on the expression of heat shock protein 72 mRNA in the rat brain / 대한해부학회지

Recently, there are numerous efforts to explain the psycho-, neurological events through molecular biological standards. Because of the property as a strong stimulant to neural cells, convulsions induced by electroconvulsive shock (ECS) or kainic acid are used for neurobiological research. In this study, the effect of systemic administration of kainic acid and ECS on the expression of hsp 72 mRNA in the rat brain was investigated with in situ hybridization histochemistry. The induction of hsp 72 mRNA was observed in the dentate gyrus from 2 hr after KA treatment. After that, the expression was gradually increased in the various areas including dentate gyrus, hippocampus, olfactory bulb, cerebral cortex, caudate-putamen, thalamus, and peaked at 9 hr after KA treatment. At the 72 hr after KA treatment, weak expression was found only in the CA3 area of hippocampus. However, the expression of hsp 72 mRNA was not detected in any ESC treated rat brains, we examined.The inducton of c-fos was observed from 15 min, peaked at 6 hr, and returned to basal level at 48 hr after KA treatment. The expression of c-fos was observed in the same areas that showed induction of hsp 72 mRNA. In the ECS treated rat brains, the induction of c-fos was found in the dentate gyrus, olfactory bulb and cerebral cortex at 15 min and 30 min after ESC. From these results, it may be suggested that the effects of KA treatment and ECS on the neuronal cells are different, and it is due to difference in induction mechanism of convulsion between KA and ECS. And, the similarity between the expression pattern of hsp 72 mRNA by KA and KA receptor suggests that the induction of hsp 72 mRNA is based on the direct effect of KA through KA receptor.

Effects of Increased Lymphocytes and B Cell Clonality of Marrow Aspirates on Marrow Involvement and Prognosis in Children with Neuroblastoma / 대한혈액학회지

BACKGROUND: The lymphocytes including morphologically immature lymphoid cells are frequently increased in the marrow aspirates of children with neuroblastoma. We studied about the clonality of these lymphoid cells and its effects on the marrow involvement and prognosis of disease. METHODS: We evaluated 30 marrow aspirates of 23 children with neuroblastoma from 1990 to 1998. We tested the immunoglobulin heavy chain gene rearrangement PCR for B cell clonality and T cell receptor gamma gene rearrangement PCR for T cell clonality with bone marrow specimens. RESULTS: Younger children showed negative bone marrow involvement more than older children. In this group, the proportions of immature lymphoid cells and total lymphocytes were higher (3.4+/-3.2% vs. 0.8+/-1.9%, 31.3+/-17.0% vs. 14.7+/-12.0%). Immunoglobulin heavy chain gene rearrangements were present in 19/30 (64%) specimens and more frequently observed in negative marrow involvement cases. Seven cases with the proportions of total lymphocytes more than 30% showed significantly high long-term survival probability (P=0.05). Ten cases with B cell monoclonality showed the tendency of high long-term survival probability (P=0.13). CONCLUSION: The increase of lymphocytes including morphologically immature lymphoid cells in the marrow aspirates of children with neuroblastoma were frequently observed in the children without marrow involvement of malignancy and closely related to B cell clonality. The increase of total lymphocytes and related B cell monoclonality may be one of possible explanations of goodprognosis of children with neuroblastoma.

The expression of new rat Ulip mRNA in the developing rat brains / 대한해부학회지

One cDNA was cloned out of developmentally differentially expressed genes in developing rat brains with ordered differential display method (ODD). The expression of cloned cDNA was observed from embryonal day 12 (E12), peaked at postnatal day 7 (P7), decreased to undetectable level at adult. By sequencing and sequence search with GenBank data, it was revealed that cloned cDNA was very similar to mouse Unc-33-like phosphoprotein (Ulip), which is known to be involved in the axonal outgrowth, thus, named as new rat Ulip (nrUlip). In situ hybridization histochemistry of developing rat brains showed that nrUlip mRNA was highly expressed in the area for differentiating neurons and the expression was observed just after neurogenesis in the various brain areas including thalamus, septal area, cerebral cortex, caudate-putamen, hippocampus, cerebellum, and dentate gyrus in the order of neurogenesis. These developmental expression pattern was well matched with the result of ODD. This may justify ODD as one of the best way to clone the genes differen-tially expressed among samples. These results and high sequence homology of nrUlip to mouse Ulip related with axonal outgrowth suggest that nrUlip may be also involved in the outgrowth of axon.

The mRNA Expression of Phosphoinositide-specific Phospholipase C-beta Isozymes in Postnatal Rat Brains / 대한해부학회지

Phosphoinositide-specific phospholipase C(PLC) is known as a key enzyme which produces two major second messengers: diacylglycerol and inositol 1,4,5 trisphosphate. Although it has been suggested that PLC beta isozymes have important roles in nervous system, less is known about the function of PLC beta in development of nervous system. We have localized the mRNA expressions of PLC beta isozymes in the postnatal rat brains by id firm hybridization histochemistry. In the postnatal rat brains, each isozyme of PLC beta showed differential expression pattern. The expression of PLC beta1 mRNA was found in various areas including olfactory bulb, cerebral cortex, caudate putamen, hippocampus, dentate gyrus, and cerebellum. In general, the expression in these areas was gradually increased after birth (PO) until postnatal day 21 (P2l) and slightly decreased to adult level. The expression of PLC beta2 mRNA was not found in postnatal rat brains. The expression of PLC beta3 mRNA was found from P0, peaked at Pl4, and decreased to adult level in the purkinje cells of cerebellum. PLC beta4 mRNA was strongly expressed in the thalamus, cerebellum, cerebral cortex, and olfactory bulb. In these areas, the expression was gradually increased after birth, peaked at P2l, and decreased to adult level. In whole body parasagittal sections of 18 day old rat embryo, PLC betal mRNA was exclusively expressed in nervous tissue, PLC beta3 and PLC beta4 were expressed in various tissues, and the expression of PLC beta2 was not found in any kind of rat tissues. From the different spatiotemporal mRNA expression patterns of PLC beta isozymes in the postnatal rat brains, it is suspected that each PLC beta isozyme may have specific role in signal transduction for postnatal development of rat brain.

CD55 and CD59 : New Diagnostic Tests for Paroxysmal Nocturnal Hemoglobinuria / 대한임상병리학회지

BACKGROUND: To diagnose paroxysmal nocturnal hemoglobinuria (PNH), the conventional methods such as sucrose lysis test and Ham's test have been used. But their sensitivities were so low that it has been difficult to confirm the diagnosis of PNH. And it has been reported that during the follow up of aplastic anemia patients, PNH clones were developed. So, we investigated the usefulness of newly introduced CD55 and CD59 tests for the diagnosis of PNH compared with conventional tests and the significance of previous history of aplastic anemia in PNH patients. METHODS: We performed the flow cytometric measurements with indirect immunofluorescence method using monoclonal antibodies to each CD55 or CD59 on the surface of red cells or neutrophils. Among fifty one patients who were requested of CD55 and CD59 tests, we reviewed the medical records of ten patients who showed the defective expression of CD55 and/or CD59 expression. RESULTS: Of ten patients who showed the defective expression of CD55 and/or CD59 expression on red cells or neutrophils, six patients were requested of sucrose lysis test also and seven patients Ham's test. Only three of six (50%) showed positive results in sucrose lysis test and two of seven (29%) in Ham's test. One showed detective CD59 expression on only neutrophils. Four (40%) had the history of aplastic anemia and two (20%) were diagnosed as aplastic anemia and PNH at the same time. Another one had the refractory anemia of excess blasts and another acute mixed lineage leukemia at the time of CD55 and CD59 tests. Two were diagnosed as PNH in the course of cytopenia workup and had no previous history of hematologic diseases. CONCLUSION: CD55 and CD59 tests are considered to be the most useful and specific tests to diagnose PNH. During the follow up of patients with aplastic anemia, CD55 and CD59 tests are valuable to detect the development of complicated PNH clones.

Bone Marrow Findings and Possible Indices of Treatment Response afterChemotherapy and/or ATRA therapy in Acute Promyelocytic Leukemia / 대한혈액학회지

BACKGROUND: For acute promyelocytic leukemia (APL), NCI criteria (1990) does not provide reliable information regarding therapeutic response. We studied APL cases in our hospital and evaluated various criteria for their predictability of therapeutic response. METHODS: Group I (GI) included 8 APL cases treated with chemotherapy and group II (GII), 10 cases with ATRA plus chemotherapy. Four treatment response indices were; (1) NCI criteria, (2) the percent sum of myelocyte and metamyelocyte (PSMM), (3) Differentiation Index[ (myelocyte+metamyelocyte+band neutrophil+segmented neutrophil)%/ (myeloblast+promyelocyte)%, DI], and (4) Maturation Index[ (metamyelocyte+band neutrophil+segmented neutrophil)%/ (myeloblast+promyelocyte+myelocyte)%, MI]. RESULTS: Among those achieving complete remission (CR), four of GI and eight of GII showed normocellularity or hypercellularity, two were in partial remission and three in persistence of GI by NCI criteria and one of GII showed persistent Auer rods at D14. Applying NCI criteria, the blast plus leukemic promyelocyte as leukemic cell were correlated well with clinical outcome. PSMM of GII were relatively constant as 20 to 29.7% at D28. DI showed wide variation and MI over 2 (Nakajima, 1996) did not correlate with CR by NCI criteria in 5 cases at D14 and 1 case at D28. CONCLUSION: NCI criteria are the reliable predictor of CR at D28 after chemotherapy if blasts plus leukemic promyelocytes are regarded as leukemic cell while they are inappropriate at D14. The persistence of Auer rods dose not exclude CR. After ATRA plus chemotherapy therapy, PSMM over 20% at D28 may be considered as a marker for CR.