Inhibition of NF-kappaB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells

Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-kappaB (NF-kappaB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-kappaB activation. Also, we determined whether selective inhibition of NF-kappaB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-kappaB or expression of a recombinant adenovirus vector encoding an IkappaB-alpha mutant (Ad-IkappaBalphaM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-kappaB activation was determined by immunohistochemical staining, NF-kappaB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-kappaB activity. Treatment with inhibitors of NF-kappaB such as MG132, PDTC or expression of Ad-IkappaB-alphaM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-kappaB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression.

Changes in Somatostatin Receptor mRNA Levels by G Protein Mutation in GH3 Cells Which Show Responsiveness to Growth Hormone-Releasing Hormone / 대한내분비학회지

BACKGROUNDS: GH3 cells lack growth hormone(GH)-releasing hormone(GHRH) receptors. In this study, GH3 cells permanently transfected with human GHRH receptor cDNA(GH3-GHRHR cells), were established in order to examine the effects of GHRH and G protein mutation(gsp oncogene) on the levels of somatostatin receptor mRNA. METHODS: GH3 cells were permanently transfected with a plasmid expressing human GHRH receptor cDNA. The GHRH receptor mRNA was detected by RT-PCR. The responsiveness to GHRH was evaluated using a GHRH binding assay, Western blot analysis, Northern blot analysis, and measurements of the intracellular cAMP levels and GH release. Cells were transiently transfected with the gsp oncogene, and then treated with GHRH or octreotide for 4h. The sst1 and sst2 mRNA levels were measured using real-time RT-PCR analyses. RESULTS: GHRH receptor mRNA was detected in the GH3 cells permanently transfected with human GHRH receptor cDNA. The GHRH binding assay showed that GHRH was bound to the GH3-GHRHR cells. The GHRH treatment increased the intracellular cAMP levels, GH release, GH mRNA levels, and MAPK activity, as well as the levels of sst1 and sst2 mRNA. Transient expression of the gsp oncogene for 48h increased the cAMP, GH release, and levels of sst1 and sst2 mRNA. In the gsp-transfected GH3-GHRHR cells, GHRH stimulation resulted in decreases in the magnitude of the increase in the levels of sst1 and sst2 mRNA compared to those transfected with a control vector. Octreotide treatment did not alter the levels of sst1 and sst2 mRNA in either the control or gsp-transfected cells. CONCLUSION: These results suggest that GH3 cells permanently transfected with the GHRH receptor are useful in the in vitro studies on the actions of GHRH. The gsp oncogene was shown to increases the levels of sst1 and sst2 mRNA in GH3 cells, but these findings are unlikely to be the major mechanism by which gsp-positive pituitary tumors show a greater response to somatostatin. The discrepancy between the in vivo and these in vitro results should be examined further.

Assessment of an Apo-1/Fas Promoter Polymorphism in Korean Schizophrenia Patients

Apoptosis has been hypothesized to be involved in the pathogenesis in schizophrenia. A large number of genes are known to mediate the apoptotic process; Apo-1/Fas (CD95) is a well-known example of such genes. In the present study, MvaI restriction fragment length polymorphism, a polymorphic marker present within the Apo-1/Fas gene, was examined in a population consisting of 226 control subjects and 110 schizophrenia patients, all of them Korean in ethnicity. No statistically significant difference in the genotypic distribution and allelic frequencies was observed between the control and the schizophrenia patient group. To find out the precise effect of Apo-1/Fas gene polymorphisms on the susceptibility to schizophrenia, further studies are warranted to investigate possible involvement of other polymorphisms with a larger sample population.

Gene Expression of Somatostatin Receptor (Subtype 2 & 5), Gi2 alpha and Pit-1 in GH-secreting Pituitary Adenomas / 대한내분비학회지

BACKGROUND: Mutation of Gs protein subunit (gsp oncogene), detected in about 30~40% of growth hormone (GH)-secreting pituitary tumors, is associated with an increased long-acting somatostatin analog octreotide sensitivity. However, the mRNA expression of somatostatin receptor (sst) was not changed in the GH-secreting pituitary tumor, regardless of whether they were gsp oncogene positive or negative. This suggests that the expression of genes coding for Gi2 alpha , Pit-1 and the other factors involved in the regulation of secretory activity in somatotrophs is likely to be altered in gsp oncogene positive tumors. We observed the impact of the gsp oncogene on the expression of the genes coding for Gi2 alpha, Pit-1 and sst (2&5) in GH-secreting pituitary tumors. METHODS: The GH response to octreotide was examined in 13 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were extracted from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gs gene. Sst2, sst5, Gi2 alpha and Pit-1 mRNA levels were measured by semi-quantitative RT-PCR. RESULTS: Sst2 and sst5 mRNA transcripts were detected in all tumors (7 gsp +, 6 gsp-). The amount of sst transcripts varied considerably varied between the tumors. There were no significant differences in sex, age, tumor size, grade or basal GH levels. Pit-1 and sst2 mRNA levels were not different. In contrast, Gi2 alpha mRNA levels were significantly higher in gsp (+) while sst5 mRNA levels were higher in gsp (-). CONCLUSION: These data suggests that gsp oncogene may increase Gi2 alpha levels but decrease sst5 mRNA levels. However, Pit-1 and sst2 mRNA expression may not be affected by gsp oncogene. The increased expression of the Gi2 alpha gene might be an inhibitory compensatory response to the action of gsp oncogene.

Gene Expression of the Somatostatin Receptors, Gi2 alpha and Pit-1 alpha in GH3 Cells Permanently Transfected with a Mutant Gs alpha Gene / 대한내분비학회지

BACKGROUND: Cyclic AMP stimulates the expression of the somatostatin (SRIF) receptor (sst1-5) and human growth hormone (GH)-secreting pituitary tumors with the gsp oncogene which increases intracellular cAMP levels, and shows a good inhibitory response of the GH to SRIF. Taken together, we hypothesized that the gsp oncogene may increase the SRIF receptor expression or and factors related to the postreceptor signal transduction of the SRIF, in order to enhance its responsiveness to SRIF. To test this hypothesis, we investigated if the gsp oncogene could increase the sst1, sst2, Gi2 alpha, and pit-1 alpha gene expression in GH3 cells. METHODS: GH3 cells were permanently transfected with the plasmid expressing Gs alpha gene, where the arginine of codon 201 was replaced with histidine. Intracellular cAMP levels and GH concentrations were measured by radioimmunoassays. Gene expressions of the sst1, sst2, Gi2 alpha, and pit-1 alpha were determined by RT-PCR. RESULTS: Intracellular cAMP levels and medium GH release were increased by 1.7 and 2.7-fold in GH3 cells expressing the gsp oncogene, respectively. In GH3 cells expressing the gsp oncogene, the sst1 mRNA levels were decreased, whereas those of the sst2, Gi2 alpha and pit-1 alpha mRNA were increased. A 4-h forskolin (10 M) stimulation remarkably increased the sst1 and sst2 mRNA levels in GH3 cells expressing wild and mutant Gs alpha . However, forskolin did not affect the Gi2 alpha and pit-1 alpha mRNA levels. In contrast, SRIF (1 M, 2 h) decreased the sst2 mRNA levels only in GH3 cells expressing the gsp oncogene. CONCLUSION: These results suggest that higher expressions of sst2, Gi2 alpha, and pit-1 alpha, induced by the gsp oncogene may be a mechanism by which gsp-positive pituitary tumors show a greater response to SRIF. The discrepancy between these and in vivo results should be explored further.

Indomethacin induces apoptosis in NCI-H1299 human lung carcinoma cells

Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to be useful in the chemoprevention of colon cancer. To investigate whether indomethacin, an NSAIDs, induces apoptosis and thus assess the possibility of its application in the chemoprevention of human lung cancer, we have performed MTT assay, TUNEL assay, DAPI staining, and flow cytometric analysis using human lung carcinoma cell line NCI-H1299. Through morphological and biochemical analyses, it was demonstrated that NCI-H1299 cells treated with indomethacin (0.5 mM) exhibit classical apoptotic features. These results suggest that indomethacin induces apoptosis in NCI-H1299 cells and that NSAIDs, including indomethacin, may be a useful tool for the chemoprevention of human lung cancer.

Thyrotropin-releasing Hormone(TRH) Receptor Gene Expression in GH3 Cells Permanently Transfected with a Mutant Gs alpha Gene / 대한내분비학회지

BACKGROUND: Gs alpha gene mutation, that constitutively increases intracellular cAMP, is found in some acromegalic patients. It was demonstrated that increased intracellular cAMP levels suppress the expression of rat TRH receptor (TRH-R) mRNA. We previously demonstrated that transient expression of a mutant Gs alpha gene suppress the rat TRH-R gene expression in the cultured rat growth hormone-secreting tumor cell line (GH3), whereas TRH-R gene expression in adenomas with Gs alpha gene mutation (gsp oncogene) did not differ from that in tumors without the mutation. The discrepancy suggests the possibilities that the effect of permanent expression of mutant Gs alpha gene on TRH-R gene expression is different from that of transient expression of the mutant gene and hypothalamic hormones including TRH regulate the gene expression. METHODS: We investigated whether permanent expression of the mutant-type Gs alpha does not suppress the TRH receptor gene expression in GH3 cells, and whether TRH suppresses the gene expression by using reverse transcription-polymerase chain reaction (RT-PCR) and in vitro transcription. RESULTS: Permanent expression of a mutant-type Gs alpha increased basal cAMP levels up to 1.7-fold relative to the controls, whereas the wild-type cell line did not show increased cAMP levels. Permanent expression of a mutant-type Gs alpha increased TRH receptor mRNA level up to 2.8 fold compared with the controls. Treatment of the permanently transfected GH3 cells with TRH suppressed TRH-R gene expression more prominently compared to the wild type GH3 cells. CONCLUSION: These results suggest that permanent expression of mutant Gs alpha enhances the expression of TRH-R in GH-secreting pituitary tumors with gsp oncogene, but the gene expression may also be regulated by other factors including TRH.

Two dinucleotide repeat polymorphisms (AC/TG and GT/CA) in the 5' upstream region of the mouse tryptophan hydroxylase gene

Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is primarily expressed in serotonergic neurons of the raphe nuclei. Simple tandem repeat polymorphisms, typically one to four nucleotides long, are tandemly repeated several times and often characterized by many alleles. To identify the presence of polymorphic repeats, we sequenced the 5'-upstream region of the mouse TPH gene. For the detection of any allelic variants, polymerase chain reaction, nonisotopic single-strand conformation polymophism, and DNA sequencing analyses of the tandem repeat sequences were performed using genomic DNA extracted from 60 ICR mice. Two dinucleotide repeats, 5'-(AC/TG)22-3' and 5'-(GT/CA)17-3', were identified at approximately -5.7 kb and -3.4 kb upstream from the transcriptional initiation site of the mouse TPH gene, respectively. Minor allelic variants, 5'-(AC/TG)21-3' and 5'-(GT/CA)18-3', were observed in heterozygous pairs from 3 of 60 and 1 of 60 ICR mice, respectively. The identification of these microsatellites in the mouse TPH promoter raises the possibility that identical and/or other polymorphic sequences might exist in the upstream region of the human TPH gene.

Radiologic and Clinical Evaluation after Arthroscopic Reconstruction of Anterior Cruciate Ligament Using Autogenous Bone-Patellar Tendon-Bone Graft

PURPOSE: The purpose of this study was to correlate radiological analysis(as divergence of femoral tun-nel and interference screw and tunnel placement) with clinical results(as physical examination, Lysholm knee scoring scale, and side to side difference of anterior displacement in an arthrometer). MATERIALS AND METHODS: This study reviewed radiological and clinical results in 48 endoscopic single-incision ACL reconstruction, using autogenous bone-patellar tendon-bone graft and interference screw fixation, between January 1995 and October 1997. We measured the femoral divergence in antero-poste-rior and lateral views of the knee(APD/LD), the angle between a line through the longitudinal axis of dis-tal femoral shaft, and the axis of femoral tunnel in antero-posterior and lateral views(APFT/LFT). We also measured the placement of a tunnel in antero-posterior and lateral views. RESULTS: Significant correlation was present between APD and APFT(negatively) and between LD and LFT(positively), while other variables had no significant correlation. Furthermore, there was no signifi-cant correlation between divergence and clinical results. Clinical results correlated positively with posteri-or femoral tunnel placement on lateral radiographs and negatively with excessive anterior tibial tunnel placement. Therefore, when femoral tunnels were placed at least 60% posterior along the Blumenssat's line and tibial tunnels were placed at least 20% posterior along the tibial plateau, 77.1% of the patients had good or excellent Lysholm score and 80% of the patients had a KT-2000 Arthrometer maximum manual side-to-side difference of 3 mmor less. When the above criteria were not met, however, only 53.8% of the patients had good or excellent Lysholm score and 53.8% had a KT-2000 Arthrometer maximum manual side-to-side difference of 3 mmor less. CONCLUSIONS: This close correlation indicated that satisfactory radiographic tunnel position influences the outcome of an ACL reconstruction.

Selective cytotoxicity of a novel platinum (II) coordination complex on human gastric cancer cell lines and normal kidney cells

We have synthesized novel platinum (II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis(diphenylphosphino)ethane (DPPE) as leaving group. Furthermore, nitrate was added to improve the water-solubility. A new series of (Pt(cis-DACH)(DPPE)) cntdot 2NO3 (PC) was evaluated its antitumor activity on various MKN-45 human gastric adenocarcinoma cell-lines and normal primary cultured kidney cells. The new platinum complex demonstrated high efficacy in the cytotoxicity on MKN-45 cell-lines as well as adriamycin-resistant (MKN-45/ADR) and cisplatin-resistant (MKN-45/CDDP) cells. The cytotoxicities of PC were found quite less than those of cisplatin in rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues using MTT assay, (3H)-thymidine uptake and glucose consumption tests. Based on these results, this novel platinum (II) coordination complex, was considered as better a valuable lead for improving antitumor activities with low nephrotoxicities in the development of a new clinically available anticancer chemotherapeutic agents.

Staging of Esophageal Cancer Using Positron Emission Tomography: Comparing to Computed Tomography / 대한흉부외과학회지

BACKGROUND: Correct preoperative staging of esophageal cancer is a prerequisite for adequate treatment. We prospectively compared the accuracy of positron emission tomography (PET) with [fluorine-18]FDG in the staging of esophageal cancer to that of computed tomography (CT). MATERIAL AND METHOD: The findings of FDG PET and of chest CT including lower neck and the upper abdomen of 20 biopsy-proven squamous cell carcinoma patients (male, 19; female, 1; mean age, 61) were compared with the pathologic findings obtained from a curative esophagectomy with lymph node dissection. RESULT: The sensitivities of FDG PET and CT for diagnosis of primary tumor were the same, 90.0% (18/20). Both FDG PET and CT failed to show the primary tumor in 2 of 20 patients; one had a 1cm sized carcinoma in situ and the other had T1 stage cancer. By using the results of the pathologic examinations of 193 removed lymph node groups, we calculated the diagnostic sensitivities, specificities and accuracies of PET and CT (*x2 p < 0.005). Sensitivity** Specificity Accuracy* PET 55.6%(30/54) 97.1%(135/139) 85.5%(165/193) CT 13.0%(7/54) 98.6%(137/139) 74.6%(144/193) One of four patients with a false-positive for PEThad had active pulmonary tuberculosis. Among the 24 tumor involved lymph node groups, PET failed to show tumor metastasis in 5 lymph node groups abutting the tumor and in 14 lymph node groups located where the decay correction was not performed. CONCLUSION: Based on the above findings, it is suggested that [F-18]FDG-PET is superior to CT in the detection of nodal metastases and in the staging of patients with esophageal cancer.

Relationship between the Expression of Growth Hormone-Releasing Hormone Receptor Gene and Endocrinologic Profiles in GH-Secreting Pituitary Adenomas / 대한내분비학회지

BACKGROUND: Growth hormone-releasing hormone (GHRH) plays a key role in the regulation of the proliferation and differentiation of somatomammotroph cells as well as secretion of GH. The actions of GHRH are mediated through the GHRH receptor (GHRH-R) that is a G protein coupled receptor with seven transmembrane domains. It has been demonstrated that alternative splicing occurs in the third cytoplasmic domain of rat and human GHRH-R mRNA, However, the clinical significance of the altemative splicing remains to be unsolved. To find an insight into the clinical significance, we investigate the correlation between the GHRH-R gene expression and a variety of clinical clinical and endocrinological findings in 11 acromegalic patients. METHODS: Eleven acromegalic patients (3 males and 8 females, mean age 43.5 years) were included in this study. Six endocrine tests were carried out to evaluate the GH seeretory function of tumors. Invasiveness of tumors were evaluated by preoperative MRI findings on the basis of Hardys classification. Sequence the gsp oncogene and estimate the GHRH-R gene expression by RT-PCR and in vitro transcription. RESULTS: Three different sized cDNA fragments, 250 bp, 700 bp and 810 bp, were found after RT-PCR. The amount of 250 bp fragment was higher than those of the other two fragments. The clinical findings (age, size, GH level, frequency of paradoxical response to TRH or GnRH, octreotide response, hypothalamic somatostatinergic activity) of the group with high expression of the 250 bp fragment did not significantly differ from those of the group with low expression. The GHRH-R gene expression of tumors with gsp oncogene did not significantly differ from that of tumors without gsp oncogene. CONCLUSION: These results suggest that the expression of GHRH-R gene may not be an important determinant for tumor growth, and the lower GH response to GHRH of tumors with gsp oncogene may not be attributed to the lower expression of GHRH-R gene. The expression of GHRH-R is likely to be regulated by a certain property of tumors for GH secretion and growth.

In vitro cytotoxicity of novel platinum(II) coordination complexes containing diaminocyclohexane and diphenylphosphines

We have synthesized new platinum(H) analogs containing 1,2-diaminocyclohexane (dach) as a carrier ligand, 1,3-bis(diphenylphosphino) propane (DPPP) /1,2-bis(diphenylphosphino)ethane (DPPE) as a leaving group and nitrates to improve solubility. In the present study, the cytotoxicity of (Pt(trans-l-dach)(DPPP))cntdot2NO3 (KHPC-001) and (Pt(trans-l-dach)(DPPE)) cntdot 2NO3 (KHPC-002) was evaluated and compared on various P-388 cancer cell lines and porcine kidney cell line (LLC-PK1). The new platinum complexes demonstrated high efficacy on P-388 mouse leukemia cell line as well as cisplatin-resistant (P-388/CDDP) and adriamycin-resistant (P-388/ADR) P-388 cell lines. The intracellular platinum content was measured by a flame atomic absorption spectrophotometer (FAAS), and it was comparable to the results of IC50 of the three complexes on LLC-PK1I and P-388/S cells, while only DPPE compound was accumulated in high volume in P-388/ADR and P-388/CDDP cells. While the DNA-interstrand cross-links of KHPC-001, KHPC-002 and cisplatin were similar on P-388/S leukemia cells, these new platinum complexes were much less DNA cross-linking to a kidney derived cell line, LLC-PK1. These results indicate that KHPC-001 and KHPC-002 are a third-generation platinum complexes with potent antitumor activity and low nephrotoxicity.

Expression of TRH Receptor Gene in GH-Secreting Piruitary Adenomas / 대한내분비학회지

Background: To test the hypothesis that Galphas gene mutation may suppress the expression of TRH-R gene, we investigated whether hTRH-R gene expression is lower in human GH-secreting pituitary adenomas with Galphas mutation than in tumors without the mutation. Method: TRH-induced paradoxical response of GH was observed in 8 acromegalic patients. The mutation of gene was identified by direct sequencing of the genomic DNA prepared from GH-secreting pituitary adenomas. The expression of hTRHT mRNA was quantitated by RT-PCR. Results: The transcript of hTRH-R gene was detected in 6 of 8(75%) tumors. Three of these(50%) showed the paradoxical GH response to TRH and the other three patients did not show the response. The relative expression of hTRH-R mRNA in the tumors from patients with the paradoxical response of GH to TRH did not differ from that in the tumors from patients without the paradoxical response. Direct PCR sequencing of Galphas disclosed a mutant allele and a normal allele only at codon 201 in 4 of 8 tumors. The paradoxical response to TRH was observed in 2 of 4 patients without the mutation, and 2 of 4 patients with the mutation. The hTRH-R gene expression of pituitary adenomas did not differ between the tumors without the mutation and those with mutation. Conclusion: This study suggests that the expression of TRH-R gene is not likely to be a main determinant for the paradoxical response of GH to TRH, and that Galphas mutation does not seem to suppress the gene expression of TRH-R in GH secreting adenoma.

Gene Expression of Somatostatin Receptor Subtype 2 and 5 in GH-Secreting Pituitary Adenomas / 대한내분비학회지

BACKGROUND: SSTR2 and SSTR5 are most frequently observed in GH-secreting pituitary tumors, and SSTR5 is believed to be more specific to mammosomatotroph lineage. Octreotide binds with high affinity to those two types. There is no report that investigates the quantitative comparison of the two subtype gene expressions, and the correlation between their gene expressions and GH response to octreotide in GH-secreting pituitary adenomas. METHOD: GH response to octreotide was examined in 8 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were prepared from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gas gene. mRNAs of SSTR2 and SSTRS were quantitated by the comparative RT-PCR and in vitro transcription. RESULTS: The in vitro transcripts of SSTR2 and SSTR5 cDNA were detected in all tumors. The amount of SSTR transcripts was considerably variable between the tumors. The amount of SSTR5 transcript was significantly smaller than that of SSTR2 transcript (0.07+-0.02 vs. 0.87+-0.10), and they did not show any correlation . There was no signicant difference in sex, age, tumor size and grade, basal GH levels, and the GH responses to octreotide between the group with high and low SSTR gene expression. No significant correlation was found between the GH response to octreotide and the amount of SSTR2 transcript, wherease the amount of SSTR5 transcripts showed a tendency of negative correlation with the octreotide response. Tumors with gsp oncogene showed significantly higher response to octreotide than those without the oncogene. The amount of SSTRS transcript in gsp-positive tumors was significantly smaller than in gsp-negative tumors (0.03+-0.01 vs. 0.12+-0.03). CONCLUSION: These results suggest that SSTRS gene expression is lower than that of SSTR2 in GH-secreting adenomas. It is probably attributed to the binding of somatostatin to SSTR5 which has a higher affinity to the hypothalamic somatostatin, Tumors with gsp-oncogene is likely to express a higher density of SSTR5 than those without the oncogene.

Surgical treatment of pulmonary aspergillosis / 대한흉부외과학회지

No abstract available.

Surgical resection of double primary cancer in esophagus & stomach / 대한흉부외과학회지

No abstract available.

A Clinical Review of Miliary Tuberculosis in Children

A Clinical study was made of 88 pediatric patients with miliary tuberculosis, who were admitted to the Pediatric Department of Kwangju Christian Hospital during the period of January, 1971 through December, 1980. 1) The incidence of miliary tuberculosis in children was 0.6%(88 cases) of the total pediatric admission cases(13969), and 12.5% (88 cases) of the total pediatric tuberculous patiens(705). 2) The highest incidence was found in those under the age of 3 years, comprising 63.7%(56 cases) of all cases. The sex ratio of male to female was 1.5:1, which is not significant. 3) The most prevalent season was Spring, with 34.1% (30 cases). 4) The source of infection was found within their family in 36.3% (32cases). 5) Only 14.8% (13 cases) had received BCG innoculation. 6) Predisposing factors were found in 24.9% (21 cases) and these were measles, chicken pox, pertussis, typhoid fever in decreasing order of frequency. 7) Chief complaints on admission in the order of frequency were:fever (72.7%), coughing (68.2%), general weakeness (37.5%), vomiting (35.2%). 8) Principal clinical features on admission were marked adnormal auscltatory findings (68.2%), emaciation (54.5%), adnormal neurologic sings (42.0%), cervical lymphaderopathy (39.8%) and hepatosplenmegaly (22.7%). 9) Tuberculin skin test was done in 55 cases and positive reaction was obtained in 21.8% (12 cases). 10) Hematologic findings revealed a mild degree of anemia in 52.3% of all patients and leukocytosis in 75.0%. 11) AFB smear was positive in only 19.3% (17 cases/88), and the highest positive rate was found in sputum (40.0%). 12) Tuberculous meningitis was the most most common disease associated with miliary tuberculosis. 40.9% (36 cases( of all miliary tuberculosis cases were complicated by tuberculous meningitis, with the highest incidence of 72.2% (56 cases) under the age of 3 years. 13) The usual treatment was the triple regimen of INH, PAS and SM, though PAS was replaced by EMB or Rifampin in recent cases, Corticosteroids were added in complicated cases. 14) In 21.6% (19 cases) of total cases, the clinical symptoms and the miliary density on X-ray disappeared after 3 months of treatment. 15) The mortality rate was 10.2% (9 cases/88).

A Follow-up Study of Newborns who had Exchange Blood Transfusion for Hyperbilirubinemia

A follow up study was made of 59 cases of neonatal hyperbilirubinemia receving blood exchange transfusion at Kwangju Christian Hospital from early 1976 to early 1979, with the following results. 1. 42patients(71.2%) returned for followup: 12 patients(20.3%) did not return; and 5 patients(8.5%) had died. 2. Of those returning, developmental status was studied by D.D.S.T. 38 patients(90.5%) had normal development , 3(7.1%) were retarded, and 1(2.4%) was questionable. 3. There was no retardation among patients exchange-Transfused at the age of 5 days or less, except for one patients with severe dehydration. All the other retarded or dying patients were over 5 days at the time of exchange transfusion. 4. Serum bilirubin level was above 27 mg% in all retarded patients . Of the 5 patients dying, 3 had serum bilirubin levels of over 40mg%, one with S.B. of 25mg% had BET at 10 days of age, and one died of necrotizing enterocolitis without evidence of kernicterus. 5. In patients with normal development, 23 were male, and 15 were female. All females had normal development, whereas all four babies with retardation were male. 6. Because S.B. remained over 25mg%, three patients underwent a second BET, with good results. 7. ABO incompatibility was etiologically responsible in 23 cases (55.9%), followed by idiopathic hyperbilirubinemia in 16 cases (27.4%), Other causes of hyperbilirubinemia were infection, respiratory distress syndrome, immune neonatal thrombocytopenia, enclosed hemorrhage, small-for-date infant, etc. 8. Mean values with standard errors of pre BET serum bilirubin level were as follows. Normal development group: 28.10.69mg% Retarded development group: 30.21.15mg% There was a tendency toward higher S.B. levels in retarded development group. 9. Nine patients who had early signs of kernicterus on admission, developed normally after BET, but those patients , shown later to be retarded, had only transient improvement of early signs of kernicterus at the time of discharge. 10. Thirty-three patients had siblings, among whom 8 also had history of hyperbilirubinemia or mental retardation due to kernicterus, or had undergone blood exchange transfusion. All of the were cases of ABO incompatibility. 11. Motor distrubance was the predominant handicap in all 4 cases of typical cerebral palsy, but no speech disturbance or hearing loss was seen. Choreoathetosis was evident in two patients over 3 years of age, but it was not possible to classify the cerebral palsy in two patients less than 1 1/2years of age.

Clinical Observations on Tuberculous Meningitis in Childhood

A clinical study was carried out on patients with tuberculous meningitis who were admitted to the Department of Pediatrics, Kwangju Christian Hospital during a 9 year period from January, 1971 to December, 1979. The following results were obtained. 1) About 3/4 of all cases were under the age of 6, the majority being between the age of one and three. The male-to-female ratio was 1.3:1. 2) Seasonal incidence was in the order of spring, summer, winter and autumn, but no sign ificant differences were noted. 3) A family history of tuberculosis was found in 41.5%, usually in one of the parents. 4) A history of B.C.G. vaccination was found in 16.7% of tuberculous meningitis cases. The tuberculin test was positive in 28.9%. 5) The most frequent symptoms on admission were vomiting, fever, convulsion and headache, in that order. 6) The major neurologic findings were unconsciousness(34.0%), neck stiffness(76.4%), and positive Kernig's sign(63.2%). 7) Leukocytes in the C.S.F. on admission were generally elevated, but below the range of 500/mm3 in 74.5% of cases, and the mean count was 278.7/mm3 with 66.7% lymphocytes. Mean protein level in the C.S.F. was 162.5mg/dl, and 94.3% of all cases were over 50mg/dl. Sugar in the C.S.F. was definitely reduced to less than 120 mEq/L in 78.3%, with the mean level being 112.8mEq/L. 8) Chest X-ray revealed tuberculous lesions in 69.8% and miliary tuberculosis was found in 36.8% of cases. 9) The highest mortality was seen in young infants. Among 26 patients of clinical stage I on admission, 21(80.3%) recovered, and 35(79.5%) of 44 patients of stage II recovered, whereas only 13(36.1%) out of 36 patients of stage III were cured. Over-all mortality rate was 5.7% of those followed.