BACKGROUND: Methylmalonic aciduria can be caused by inherited defects in the methylmalonyl-CoA mutase enzyme, Inherited defects in the metabolism of vitamin Bl2 and acquired or inherited vitamin Bl2 deficiency. Quantitation of urinary methylmalonic acid (MMA) is very useful In diagnosis of methylmalonic acidemia and cobalamin deficiency. We evaluated a quantitation method of urinary MMA and determined reference values. METHODS: The method involved stable isotope dilution gas chromatographymass spectrometry (GC-MS) with (methyl 2H3)-MMA as the internal standard. We determined the detection limit, linearity and periodic variations of the assay. Urinary MMA levels were measured in 70 individuals of ages newborn to 58 years with no metabolic disorders. RESULTS: The lower limit of detection calculated from blank runs (mean+/-3SD) was 2.62nmo1/m1. One control urine tramp)e analyzed 23 times within 3 weeks game results of 7.83+/-1.09 (mean+/-SD, CV=13.8%) nmol/mL. The linearity at four different concentrations of MMA was acceptable (R2=0.9992). The concentration of urinary MMA in 70 individuals was 2.33+/-2.19 mmol/mol creatinine (mean+/-SD). Age related reference values which decreased with age were also reported (p=1.23x10-9). CONCLUSIONS: The described method is sensitive, specific and noninvasive, which is considered the gold standard method for measuring MMA. The method could be used as a screening test for cobalamin deficiency and inherited methyl malonic acidemia. On the basis of the narrow range of normal concentration, it is expected that the method would readily detect mild cobalamin deficiency.
Chromatography, Gas* ; Creatinine ; Diagnosis ; Gas Chromatography-Mass Spectrometry* ; Humans ; Infant, Newborn ; Limit of Detection ; Mass Screening ; Metabolism ; Methylmalonic Acid* ; Methylmalonyl-CoA Mutase ; Reference Values ; Spectrum Analysis ; Vitamin B 12 ; Vitamins

BACKGROUND: Therapeutic drug monitoring (TDM) has been shown to be effective in minimizing the risk for toxicity and maximizing the efficacy of the drugs. The application of pharmacokinetics principles to indiviualization and optimization of dosage is necessary. We evolved interpretative report system of digoxin determination in a view of individual's pharmacokinetics. The alto of the present study is to validate the effectiveness of the interpretative report system in digoxin therapeutic monitoring service. METHODS: We reviewed 125 inpatients of two groups. 4 group, before interpretative reporting, had 86 inpatients from February 1996 to March 1996. B group included 39 inpatients from September 1996 to October 1996 after the practice of the sytem. Digoxin concentrations were measured in serum by TDxFlex (Abbott Laboratories, U.S.A.). Each patient's digoxin pharmacokinetics was determined by using the Abbott-base Pharmacokinetics system (Abbott Laboratories, U.S.A.) . The interpretation for the assayed digoxin level, the recommendation of maintenance dosage and the simulation graph with predicted serum levels were included in the report. The effectiveness of the reporting system was evaluated by comparing the appropriateness of digoxin level measurement between both groups. RESULTS: It revealed that appropriate measurements of digoxin level were 59.5 % of the tests in A group and 77.1% of those in B group (p=0.006). Evaluation of serum digoxin concentrations stratified by digoxin concentration showed also significant difference among the percentage of tests in each concentration range between both groups (p=0.011). CONCLUSIONS: Interpretative report system for the assayed results caused to increase in the appropriateness of digoxin measurement. The report system with some improvement which is achieved through the active approach to physician helps us use TDM effectively. The system can be applied to the other TDM drugs.
Digoxin ; Drug Monitoring* ; Humans ; Inpatients ; Pharmacokinetics

BACKGROUND: Therapeutic drug monitoring (TDM) has been shown to be effective in minimizing the risk for toxicity and maximizing the efficacy of the drugs. The application of pharmacokinetics principles to indiviualization and optimization of dosage is necessary. We evolved interpretative report system of digoxin determination in a view of individual's pharmacokinetics. The alto of the present study is to validate the effectiveness of the interpretative report system in digoxin therapeutic monitoring service. METHODS: We reviewed 125 inpatients of two groups. 4 group, before interpretative reporting, had 86 inpatients from February 1996 to March 1996. B group included 39 inpatients from September 1996 to October 1996 after the practice of the sytem. Digoxin concentrations were measured in serum by TDxFlex (Abbott Laboratories, U.S.A.). Each patient's digoxin pharmacokinetics was determined by using the Abbott-base Pharmacokinetics system (Abbott Laboratories, U.S.A.) . The interpretation for the assayed digoxin level, the recommendation of maintenance dosage and the simulation graph with predicted serum levels were included in the report. The effectiveness of the reporting system was evaluated by comparing the appropriateness of digoxin level measurement between both groups. RESULTS: It revealed that appropriate measurements of digoxin level were 59.5 % of the tests in A group and 77.1% of those in B group (p=0.006). Evaluation of serum digoxin concentrations stratified by digoxin concentration showed also significant difference among the percentage of tests in each concentration range between both groups (p=0.011). CONCLUSIONS: Interpretative report system for the assayed results caused to increase in the appropriateness of digoxin measurement. The report system with some improvement which is achieved through the active approach to physician helps us use TDM effectively. The system can be applied to the other TDM drugs.
Digoxin ; Drug Monitoring* ; Humans ; Inpatients ; Pharmacokinetics

No abstract available in English.

Carcinosarcomas of the female genital tract have generally been regarded as a type of sarcoma. Recent studies, however, suggest the tumor may be more closely related to carcinoma and may represent metaplastic carcinoma in histogenesis. We analyzed clinicopathologic and immunohistochemical features of 10 carcinosarcomas to evaluate the relative importance of the carcinomatous and sarcomatous components in metastasis and recurrence. The primary tumor originated in the uterine body in seven cases, the uterine cervix in two and the ovary in one. Patient,s ages ranged from 54 to 71 years (mean, 64). The most common symptom of the uterine mass was vaginal bleeding. The median survival time was 21 months following diagnosis in five cases. Surgico-pathologic FIGO stages of five patients who received an operation were stage III and IV, but clinical FIGO stage of three patients (60%) among them were I. Lymphovascular invasions were identified in seven areas; five vascular invasion lesions showed the carcinomatous component alone, one the sarcomatous component alone, and remained one admixture of both components. Metastatic and recurrent lesions to the paraaortic lymph node, ovary, pelvic wall, or vaginal vault showed characteristically carcinomatous component only. Immunohistochemically, positive reactions for cytokeratin and epithelial membrane antigen were noted in the sarcomatous component of five cases. Vimentin positivity was detected in carcinomatous component of three cases. We conclude that the dominant element in carcinosarcomas of the female genital tract is the carcinomatous component. The survival rate of carcinosarcoma is extremely poor. The surgico-pathologic stage is better indicator of survival than the clinical stage. Immunohistochemical findings suggest that carcinosarcoma may represent a metaplastic carcinoma in histogenesis.
Carcinosarcoma* ; Cervix Uteri ; Diagnosis ; Female* ; Humans ; Keratins ; Lymph Nodes ; Mucin-1 ; Neoplasm Metastasis ; Ovary ; Recurrence ; Sarcoma ; Survival Rate ; Uterine Hemorrhage ; Vimentin

Rud's syndrome (RS), basically composed of ichthyosis, mental deficiency and hypogonadism, is a rare hereditary disease. Some varying dermatologic, neurologic, endocrinologic, ophthalmologic and musculoskeletal abnormalities have coincided with RS. No case of RS has been documented from Asian countries except one from Japan. We describe a 16-year-old girl who presented with lamellar ichthyosis, mental retardation, hypogonadism, short stature, alopecia, sparse eyebrows, strabismus, cataracts, and congenital dislocation of the hip. To our knowledge, RS coexisting congenital dislocation of the hip herein is the first case in English literature.
Adolescent ; Alopecia ; Asian Continental Ancestry Group ; Cataract ; Dislocations ; Eyebrows ; Female ; Genetic Diseases, Inborn ; Hip ; Humans ; Hypogonadism ; Ichthyosis ; Ichthyosis, Lamellar ; Intellectual Disability ; Japan ; Musculoskeletal Abnormalities ; Strabismus

No abstract available.
Broad Ligament* ; Female ; Leiomyosarcoma*

BACKGROUND: Unexpected deaths of the patients at ED are surprising to the medical staffs as well as the families. It may also increase the possibilities of medico-legal problems. This study was conducted to review the unexpected death in ED and find the predictive factors leading patients to unexpected death. METHODS: A retrospective study with reviewing available medical records of 183 patients who were expired at ED of Shinchon Severance Hospital from Mar. 1997 to Feb. 1998 and 103 patients of Youngdong Severance Hospital from Mar. 1996 to Feb. 1998 was done. Analyses were 4one on 30 variables of physical findings, laboratory results, procedures and therapies. We used univariate analysis, such as t-test and x2-test and multiple logistic regression analysis. RESULTS: Of the total 286 deaths in ED, 153 cases were enrolled in this analysis. The number of unexpected deaths were 76. Age, mental status, fraction of neutrophil count, BUN level, whether endotracheal incubation was done, use of inotropics were the factors with statistical ,significance on the univariate analysis, but only comatose mentality, endotracheal incubated case, and use of the inotropics were significant on logistic regression analysis. The longer the ED length of stay, the higher the rate of mortality and unexpected death. CONCLUSION: This result suggest that medical attention is needed on the patients with comatose decreased mental stylus, endotracheally intubated case and needing inotropic agents to prevent unexpected deaths. Shortening the ED length of stay may also be a factor for decrease the unexpected death rate.
Coma ; Emergencies* ; Emergency Service, Hospital* ; Humans ; Length of Stay ; Logistic Models ; Medical Records ; Medical Staff ; Mortality ; Neutrophils ; Retrospective Studies

OBJECTIVE: Behcet? disease (BD) is a chronic inflammatory disorder affecting several organs. The etiology of BD remains unclear, although genetic factors, infectious agents, and immune mechanisms have been studied. The association of BD with certain genetic factors, especially HLA-B51 antigen, is well known in some geographical areas. Nevertheless, the familial occurrence of BD is rare. In this paper, HLA phenotype was evaluated in one family member showing the clustering of BD. METHODS: The serological tissue typing of HLA class I and class II antigens was performed by standard National Institutes of Health microlymphocytotoxicity method in seven family members in which four siblings were affected by BD. The diagnosis of BD was established by the criteria of the International Study Group of BD in these four siblings. RESULTS: In this family study, all members had HLA-A2 and DQ3 antigens. Although HLA-B51 antigen was positive in six out of seven family members, BD was developed in three of the six having HLA-B51 antigen. Three siblings had the exact same HLA phenotype. However, only one person had BD among three siblings with identical HLA phenotype. In addition, all siblings who developed erythema nodosum-like lesion had HLA-B51 antigen. CONCLUSION: This family suggests that the familial clustering of BD may not be explained solely by a susceptible HLA phenotype. The environmental factor or other genetic factors besides HLA-B51 might play a role in the development of BD. Furthermore, more studies and information will be needed to clarify the role of A2 and DQ3 antigens in BD.
Diagnosis ; Erythema ; Histocompatibility Antigens Class II ; Histocompatibility Testing ; HLA Antigens* ; HLA-A2 Antigen ; HLA-B51 Antigen ; Humans ; National Institutes of Health (U.S.) ; Phenotype ; Siblings

BACKGROUND: The dose-responses of neuromuscular blocking agents may be influenced by many factors including age and inhalation anesthetics. This study was designed to determine the dose-response relationships of a new, short-acting muscle relaxant, mivacurium during nitrous oxide-halothane or nitrous oxide-enflurane anesthesia in two age groups, infants and 1 to 6 years old preschool children. METHODS: Neuromuscular blockade was monitored by recording the accelerographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relationships, 24 infants or children of two anesthetic subgroups for each age group received single bolus doses of 45~100 g/kg of mivacurium. The ED50 and ED95 were estimated from linear regression plots of log-dose vs probit of twitch depression. The lag time, onset time and maximal depression of twitch height for the selective medium dose were mesured. RESULTS: The ED50 and ED95 for the infants group were 38.2 and 53.3 g/kg during halothane anesthesia, and 29.8 and 48.6 g/kg during enflurane anesthesia, respectively. And, those for preschool children group were 49.4 and 90.7 g/kg during halothane anesthesia, and 32.3 and 81.4 g/kg during enflurane anesthesia, respectively. There was a parallelism of the dose-response curve between halothane and enflurane anesthesia in either age group. Also, there was statistically significant difference in the maximal twitch depression for the selective medium dose of mivacurium between halothane and enflurane anesthesia in either group. CONCLUSIONS: The potency of mivacurium during enflurane anesthesia is higher than that during halothane anesthesia in infants and preschool children, and during either inhalation anesthesia the dose of mivacurium is less required in infants than preschool children.
Anesthesia* ; Anesthesia, Inhalation ; Anesthetics, Inhalation ; Child ; Child, Preschool* ; Depression ; Enflurane* ; Halothane* ; Humans ; Infant* ; Linear Models ; Neuromuscular Blockade ; Neuromuscular Blocking Agents ; Ulnar Nerve