Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases

Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make the exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mtDNA mutations in 61 Korean unrelated families (or isolated patients) with MELAS or MERRF. In particular, the mtDNA sequences were completely determined for 49 patients. From the mutational analysis of mtDNA obtained from blood, 5 confirmed pathogenic mutations were identified in 17 families, and 4 unreported pathogenically suspected mutations were identified in 4 families. The m.3243A>G in the tRNA(Leu(UUR)) was predominantly observed in 10 MELAS families, and followed by m.8344A>G in the tRNA(Lys) of 4 MERRF families. Most pathogenic mutations showed heteroplasmy, and the rates were considerably different within the familial members. Patients with a higher rate of mutations showed a tendency of having more severe clinical phenotypes, but not in all cases. This study will be helpful for the molecular diagnosis of mitochondrial diseases, as well as establishment of mtDNA database in Koreans.

Clinical Course of Idiopathic Central Diabetes Insipidus in Adults / 대한내분비학회지

BACKGROUND: Idiopathic Central Diabetes Insipidus in children or adolescents requires a frequent follow-up regimen using serial brain MRI and CSF examinations especially if an isolated pituitary stalk thickening or loss of a hyperintense signal in the posterior pituitary lobe is observed. Although a detailed description has not been made in adults who had Idiopathic Central Diabetes Insipidus, the clinical course of a Central Diabetes Insipidus in children or in adolescents can not be applied to adults because a follow-up study is so invasive and expensive. In this report, we evaluated the clinical course of Idiopathic Central Diabetes Insipidus in adults. METHODS: The diagnosis of Idiopathic Central Diabetes Insipidus was based on the presenting clinical symptoms, the water deprivation test, biochemical studies and a brain MRI. We measured the urine specific gravity, urine and plasma osmolarity, electrolytes, and daily urine amount and we also performed an anterior pituitary evaluation. Patients had contrast-enhanced MRI and biochemical studies every 4 to 12 months. RESULTS: The patients included 8 females and 4 males. Their ages ranged from 20 to 76 years and their mean age was 45+/-17 years. Tumor markers in the CSF were not detected any of the patients. An anterior pituitary evaluation showed that four patients had hyperprolactinemia, and five patients had impaired secretory responses of Growth Hormone to an insulin induced hypoglycemia. Nine of the 12 patients had thickening of the pituitary stalk, seven had lacked the hyperintense signal of a normal neurohypophysis. The abnormalities of MRI disappeared in 3 patients by the 4th, 27th and 36th month follow up periods, respectively. The follow up duration was between 8 months and 11 years 3 months and the mean follow up duration period was 50.6+/-45.5 months. Clinical symptoms were corrected by DDAVP administration. Other symptoms were absent. CONCLUSION: In our study, of Idiopathic Central Diabetes Insipidus in adults there were no observed germinomas or other disease that were observed. Therefore this disorder may have a benign course.

A Case of an Organoaxial Type of Chronic Gastric Volvulus / 대한소화기내시경학회지

Gastric volvulus is a rotation of the stomach of at least 180 associated with a closed loop obstruction. Pare described the first case of gastric volvulus m 1579. Laxity of the gastric ligament, a congenital or acquired diaphragmatic defect, increased abdominal pressure, and a genetic component contributing to gastric volvulus. Gastric volvulus has been classified clinically as acute and chronic gastric volvulus, and can be classified anatomically as organoaxial, mesenteroaxial or a mixed type. Gastric volvulus occurs in children usually before 1 year of age or elderly patients. In acute gastric volvulus, and be patients complain of sudden abdominal or chest pain. The chest pain, which can radiate to the arms and neck accompanied by dyspnea, may initially lead to consideration of ischemic heart disease. Chronic gastric volvulus is difficult to diagnose because it may be associated with mild and nonspecific symptoms such as epigastric discomfort, fullness or heartburn. We experienced a case of 83 year old male with an organoaxial type of chronic gastric volvulus, iagnosed by upper gastrointestinal series, and treated with conservative rnanagement.

A Case of Crohn's Disease with Blood Pressure Falling Intestinal Bleeding / 대한소화기내시경학회지

Life-threatening gastrointestinal hemorrhage is a rare complication in Crohn's disease. The authors experienced a case of Crohn's disease manifested with massive lower intestinal bleeding. A 22-year-old woman, who had underwent small bowel resection for bowel perforation and intestinal fistula, was admitted with lower abdominal pain and massive hernatochezia. A radioisotope bleeding scan and mesenteric angiography revealed suspi- cious intestinal bleeding in the small bowel area. The colonoscopy showed multiple shallow ulcers at the terminal ileum and scars on the cecum. In spite of medical management with the diagnosis of Crohn's disease, she continuecl to rebleed and required fistuloplasty and ileal resection. In the surgical specimen was discovered multiple exposed small vessels and diffuse blood oozing at terminal ileum. After surgery, there were no more bleeding episodes and she recovered with the aid treatment of sulfasalazine and prednisolone.

Comparison of Treatment Modalities in Hyperprolactinemia / 대한내분비학회지

BACKGROUND: Prolactinomas have been treated primarily with bromocriptine, a dopamine agonists, rather than by transsphenoidal pituitary adenomectomy. However, lower success rates, as well as intolerance or resistance to medical therapy, have been reported in some recent series. The purpose of this study was to compare the effects of surgery and bromocriptine in the treatment of prolactinomas patients. Also we investigated the natural history and effects of bromocriptine on patients with idiopathic hyperprolactinemia. METHEODS: We retrospectively compared the effects of treatment with surgery and with bromocriptine in 27 idiopathic hyperprolactinemia patients, 35 microprolactinoma patients and 61 macroprolactinoma patients. RESULTS: (1) In 14 patients with untreated idiopathic hyperprolactinemia, 8 (57%) achieved remission. In patients without remission, preoperative serum prolactin level was significantly higher than patients with remission (p<0.05). In 13 patients on bromocriptine, 11 (85%) achieved remission, while the other 2, taking bromocriptine irregularly because of side effects, had persistent hyperprolactinemia. (2) In 35 patients with microprolactinoma, 11 (30%) surgery as initial therapy and surgical remission was achieved in only 5 of the 11 (45%). In 23 patients on bromocriptine, 17 (74%) achieved remission. Among the 6 patients without remission, 5 patients took bromocriptine irregularly because of side effect. (3) In 61 patients with macroprolactinoma, 49 (80%) underwent surgery as initial therapy and surgical remission was achieved in only 9 of the 49 (18%). In 50 patients on bromocriptine, 30 (60%) achieved remission. Among the 20 patients without remission, 13 took bromocriptine irregularly because of side effect and 5 were resistant to bromocriptine. CONCLUSION: In idiopathic hyperprolactinemia, the requirement for medical treatment is doubtful because of a high tendency to ward spontaneous cure. In spite of the low success rate, surgery has been used as the primary therapy for prolactinoma in Korea. And yet, medical treatment with bromocriptine is superior to surgery. However, irrgular administration of medication due to drug side effects was the main cause of the low success rate. Therefore, the necessity for new drug development is emphasized

Kallmann's Syndrome Associasted with Slipped Capital Femoral Epiphysis / 대한내분비학회지

The Kallmanns syndrome is the most common form of isolated hypogonadotropic hypogonadism in which anosmia or hyposmia resulting from agenesis of hypoplasia of the olfactory lobes is associated with LHRH deficiency, This syndrome is genetically heterogeneous and can be trans-mitted as an X-linked, autosomal dominant or autosomal recessive trait. The hypogonadotropic hypogonadism results in absent or incomplete pubertal development and may be associated with anosmia or hyposmia, mid-line defect(color blindness, cleft-lip or

Right-side Bochdalek Hernia with Unusual Kidney Herniation in an Old Patient / 대한내과학회지

Bochdalek hernia through Bochdalek foramen, defect at the posterolateral side of the diaphragm is one of the congenital diaphragmatic hernias. It usually occurs in infants, but very rare in old age and also on the right side. We experienced the right-side Bochdalek hernia including kidney herniation in 68 years old man man ifested by hemoptysis. CT scan revealed diaphragmatic defect and herniated liver, colon and kidney. Thoracotomy was performed and the 10 cm-sized large defect was closed with patch. After then, the patient has been well without symptom.

Diagnosis of Cushing's Disease by Inferior Petrosal Sinus Sampling (IPSS): Evidence of False Negative Results / 대한내분비학회지

BACKGROUND: While inferior petrosal sinus sampling (IPSS) correctly diagnoses pituitary dependent Cushings syndrome if a significant ratio of plasma ACTH between the IPS and the peripheral blood is demonstrated, little has been said about the significance of a negative ratio in Cushings disease (e.g. false negative result). We evaluated the results of IPSS with Cushings disease, and compared them with imaging findings through transsphenoidal surgery. METHODS: 29 patients with Cushings disease underwent transsphenoidal examination of the pituitary gland from 1989 to 1998 at Seoul National University Hospital were evaluated. We compared the results of IPSS and imaging findings with sellar CT or dynamic MRI. The ratio of the ACTH concentrations at the IPS and in the peripheral blood (IPS:P ratio) and the ratio of the ACTH concentrations between the IPSs (interpetrosal ratio) were calculated before and after CRH infusion. RESULTS: With IPSS the diagnosis of Cushings disease was possible in 90% (26/29), and 3 cases in whom IPSS did not show significant IPS:P ACTH ratio were confirmed to be Cushings disease through hemihypophysectomy of lesion suspected by sellar dynamic MRI and achieved remission after operation (e.g. false negative result of diagnosis for Cushings disease by IPSS). However, accurate localization of microadenoma was achieved in only 59% (17/29). Imaging study detected microadenoma in 76% (22/29) and correctly localized in 66% (19/29). Both IPSS and imaging study precisely localized the pituitary microadenoma in 10 (34.5%) cases of 29 cases and a discrepancy between two studies existed in 7 (24.1%) cases in which the imaging study correctly localized microadenoma in 6 cases and IPSS in 1 case. CONCLUSION: Only when a significant IPS:P ACTH ratio is present can Cushings disease be established by IPSS. The absence of a significant IPS:P ACTH ratio does not necessarily imply ectopic secretion of ACfH, nor does it exclude Cushings disease. The results of lateralization by IPSS do not remove the need for transsphenoidal examination of the sella turcica because false negative result can be. IPSS and radiologic study should be complementary used in diagnosis of Cushings disease and localization of microadenoma, as IPSS can be used when sellar imaging study failed to visualize the lesion and hemihypophysectomy of suspected lesion by imaging study can be considered when IPSS did not show significant ratio of ACTH.

Clinical Usefulness of 24-hour Ambulatory Blood Pressure Monitoring in Hypertensive Pregnancy / 대한내과학회지

OBJECTIVES: In the third trimester hypertensive pregnancies, we would like to evaluate effects of white coat hypertension, severity of hypertension and diurnal variation of blood pressure on the fetal outcome by using 24- hour ambulatory blood pressure monitoring. METHODS: Hypertensives(n=50) and normotensives (n=14) in the third trimester of the pregnancy underwent 24-hour ambulatory blood pressure monitoring. We excluded hypertensives(n=5) who became pre-eclampsia patients. Hypertensives(n=45) were classified as white coat hypertensives(n=14, mean ambulatory blood pressure 160 mmHg or diastolic blood pressure >100mmHg) and mild hypertensives(n=26). Sustained hypertensives were also divided into two groups which had diurnal variation of blood pressure or not. To exclude effects of hypertension severity, effects of diurnal variation were evaluated in hypertensives with similar mean arterial blood pressure. Gestational age, body weight, body weight for gestational age were used as parameters of the fetal outcome. RESULTS: 1) The prevalence of white coat hypertension was 28%(14/50). 2) There were no significant differences in the fetal outcome between normotensives(n=14) and white coat hypertensives(n=14). 3) Body weight of fetus and body weight for gestational age in moderate to severe hypertensives(n=5) were less than those of mild hypertensives(n=26), but gestational age was not significantly different between two groups. 4) Body weight of fetus and body weight for gestational age in sustained hypertensives without diurnal variation(n=10) were less than those with diurnal variation(n=8), but gestational age was not significantly different between two groups. 5) All hypertensives who became pre-eclampsia (n=5) were severe hypertensives and had no diurnal variation of blood pressure. CONCLUSION: White coat hypertension in the third trimester was quite often and did not affect on the fetal outcome. The more severe hypertension and/or absence of diurnal variation of blood pressure caused poor fetal outcome. Patients who became pre-eclampsia were severe hypertensives and had no diurnal variation of blood pressure. Ambulatory blood pressure monitoring may have several roles in the antenatal management of hypertenison.

The Comparison of the Urine RBC Phase Contrast Microscopy and Immunoperoxidase Stain in Differentiation of Hematuria / 대한신장학회잡지

Differentiation of renal(RH) and non-renal(NRH) hematuria is important in the diagnosis and treatment of the patients with hematuria. Recently, urine RBC immunoperoxidase(IPx) staining method was developed, but there was no report on the usefulness of IPx in Korea. We validated the usefulness of IPx by comparing with the PCM. Both PCM and IPx were performed at the same time in 26 patients with RH confirmed by renal biopsy and 23 patients with NRH confirmed by radiologic and/or pathologic studies who were admitted to Chungbuk National University Hospital from January 1996 to December 1996. The age of RH and NRH group were 36.6+/-15.0 and 56.5+/-22.2 years. 35.7+/-30.4% of urine RBC were stained by IPx in RH group and only 1.6+/-4.4% were stained in NRH group(P<0.001). 23.4+/-29.9% of urine RBC by PCM were counted as dysmorphic RBC in RH group and 5.7+/-13.6% were counted in NRH group(P<0.05). At the cut-off value of 20%, the sensitivity and specificity of IPx were 57.7% and 100%. At the cut-off value of 30%, those of PCM were 30.9% and 95.7%, respectively. When comparing overall test performance by calculating AUCs of ROC(receiver operating characteristics) curve, IPx was better than PCM. IPx was better than PCM in localizing the origin of hematuria. The NRH might be excluded when IPx(+) cells are more than 20% of total urine RBC.