BACKGROUND AND PURPOSE: Cerebrovascular reactivity (CVR) can be estimated by measuring the change of cerebral blood flow that occurs during vasostimulation. To estimate the cerebrovascular reactivity, we investigated the change of flow velocity of the internal carotid artery (ICA) and the middle cerebral artery (MCA) during hyperventilation and hypoventilation with the transcranial doppler. So we studied whether the CVR measured by this method could show a significant difference between the normal and the atherosclerotic subjects and whether the CVR may decrease with age in normal gubjects. METHODS: Using transcranial doppler, we measured the mean velocity (Vm), the pulsatility index (P.I.) at the resting state, the end of breath-holding and the end of hyperventilation in 30 normal and 10 atherosclerotic subjects, so we calculated the percentile change of mean velocity (% Vm) and P.I. (% P.I.) after the vasostimulation. We estimated the change of Vm, P.I., % Vm and % P.I. By the age group and compared those parameters between the age-matched normal control and atherosclerotic subjects. RESULTS: The Vm in ICA and MI significantly decreased with age (p<0.01), but there was no significant difference in Vm and P. I. Between normal and atherosclerotic subjects. The % Vm and % P.I. In response to hyperventilation significantly decreased with age in ICA, M1, M2 and there was significant difference in % Vm of ICA and M1 after breath-holding and % Vm of ICA after hyperventilation between the normal and atherosclerotic subjects. CONCLUSION: The breath-holding and hyperventilation tests could be non-invasive and useful methods in estimation of the cerebrovascular reactivity and could be applied in the basal and follow-up evaluation of the cerebrovascular reserve of the ischemic stroke patients.
Carotid Artery, Internal ; Humans ; Hyperventilation ; Hypoventilation ; Middle Cerebral Artery ; Stroke

No abstract available.
Aorta, Thoracic* ; Rupture*

OBJECTIVE: To define the incidence, the prognosis, and the risk factors of neurologic complications of open heart surgery. Background. Open heart surgery poses many hemodynamic, embolic, and metabolic threats to the brain with multiple factors relating to neurologic complications. Despite the progress in surgical technique, neurologic complications remain major causes of morbidity and occasional mortality. METHODS: Data were obtained from the charts of 297 patients submitted to open heart surgery at SNUH in 1993. We analysed the risk factors for CNS complications and identified the incidence, the type, and the results of the complications. RESULTS: Among 297 patients, CNS complications occurred in 34 patients(11.4%). The incidences of each complication were as follows. ; 6 anoxic encephalopathies(17.7%), 12 encephalopathies of uncertain etiology(35.3%), 7 seizures (20.6%), 6 TIAs or. Infarctions(17.7%), and 3 other complications(8.8%). Of the 34 patients, there were 6 deaths (17.7%), 1 vegetative state(2.9%), 1 major neurologic deficit(2.9%), 3 minor neurologic deficits(8.8%), and full recovery in 23 patients(67.7%). The risk factors such as age, presence of thrombi, type of operation, duration of bypass, duration of aortic clamping time, use of total circulatory arrest, re-operation, and use of ventricular assist device were statistically significant. CONCLUSION: The CNS complications of open heart surgery are infrequent but still remain important causes of morbidity and mortality. Evaluating the risk factors could be of help to prevent the CNS complications.
Brain ; Constriction ; Heart* ; Heart-Assist Devices ; Hemodynamics ; Humans ; Incidence ; Mortality ; Prognosis ; Risk Factors ; Seizures ; Thoracic Surgery*

PURPOSE: We determined the clinical significance of telomerase activity and telomere length in breast cancer patients and also developed the measuring system of telomerase activity change with RNAse A pre-treatment. MATERIALS AND METHODS: We measured the telomerase activity in 71 breast cancer tissues and paired normal tissues with TRAP (Telomeric Repeat Amplification Protocol) assay. Telomerase activity was calculated by computer-assisted densitometry compared to telomerase activity of the 293 control cell line. To develop the measuring system of telomerase activity modulation, we measured the telomerase activity after the treatment with RNAse A, 150microgram/ml, which inhibited 70% of telomerase activity compared to control in the 293 control cell line. In 59 paired tissues with telomerase activity, terminal restriction fragment (TRFs) length were measured using Southern blotting. RESULTS: Sixty-three out of 71 cancer tissues showed telomerase activity (88.7%), while no telomerase activity was detected in their paired normal tissues. Telomerase activity was correlated to the node metastasis (p=0.02) and stage (p=0.005), but not to the tumor size or the hormonal receptor status. TRFs were neither specific to tumor tissues nor related to any of the clinical parameters. However, changes of TRFs of the tumor tissues from their paired normal tissues were correlated to the telomerase activities. Also the patients with different TRFs between cancer and normal tissues were in more advanced stage. After pre-treatment with the 150microgram/ml of RNAse A, telomerase activity in the tumor tissues showed variable inhibition. Relative inhibition, the ratio of inhibited telomerase activity in each tumor tissue compared to the inhibition of 293 control cell line, was proportional to the telomerase activity. CONCLUSION: In breast cancer, telomerase activity was specific to the tumor tissues and correlated to tumor progression. A combination of telomerase activity and TRFs changes can be used as a guidline in detecting a better candidate for telomerase inhibition. Semi-quantitative assay with RI system can be used in evaluating the changes of telomerase activity after treatment with a new telomerase inhibitor with TRAP assay.
Biological Therapy* ; Blotting, Southern ; Breast Neoplasms* ; Breast* ; Cell Line ; Densitometry ; Humans ; Neoplasm Metastasis ; Ribonuclease, Pancreatic ; Telomerase* ; Telomere

BACKGROUND: Coronary artery bypass graft (CABG) surgery is performed more frequently than before in Korea. Central nervous system (CNS) complications are often the major prognostic determinants following the surgery. We carried out a prospective study to clarify the incidence and risk factors of neurologic complications after CABG surgery. METHODS: A consecutive series of 150 patients undergoing 152 CABG operations from March 1995 to July 1997 by one cardiac surgeon was evaluated by a team of neurologists before and after the surgery. The patients received extensive preoperative examinations including the evaluation of intracranial & extracranial cerebral artery disease. RESULTS: In 44 operations (28.9%), we detected various neurologic complications, including encephalopathy (36 operations, 23.7%), cerebral infarction (5 operations, 3.3%), and seizure (7 operations, 4.6%). Eight patients died postoperatively including one due to neurologic complication. On univariate analysis, age, degree of intracranial artery disease (ICAD), duration of bypass time, hypotension index, duration of ventricular assistant device (VAD), intraoperative event, intra- or postoperative arrhythmia, reoperation, and postoperative bleeding were statistically significant risk factors of CNS complications (p< 0.05). After multivariate analysis, however, age alone remained significant (p=0.02). The degree of ICAD showed marginal significance (p=0.06). CONCLUSIONS: The incidence of CNS complication in the patients undergoing CABG surgery was 28.9%. Our results showed that age was an independent risk factor of CNS complications. And the possibility of ICAD as a risk factor was suggested. Further study with a large number of patients would be necessary to prove the above suggestion.
Arrhythmias, Cardiac ; Arteries ; Central Nervous System* ; Cerebral Arterial Diseases ; Cerebral Infarction ; Coronary Artery Bypass* ; Coronary Vessels* ; Hemorrhage ; Humans ; Hypotension ; Incidence ; Korea ; Multivariate Analysis ; Prospective Studies ; Reoperation ; Risk Factors ; Seizures ; Transplants

PURPOSE: Intravenous 5-Fluorouracil (5-FU) and oral doxifluridine were compared with respect to therapeutic efficacy, drug toxicity, and quality of life to clarify the efficiency of oral doxifluridine. METHODS: One hundred sixty-six (166) patients who underwent a curative resection for TNM stage II and III rectal cancer between Oct. 1997 and Feb. 1999 were randomized to receive intravenous 5-FU (450 mg/m2/day) or oral doxifluridine (700 mg/m2/day) in combination with leucovorin (20 mg/m2/day). 5-FU was infused intravenously 5 consecutive days per month for a total of 12 cycles (IV arm, N=74) in one group, and doxifluridine was given orally daily for 3 weeks with a rest of 1 week for a total of 12 cycles (Oral arm, N=92). Drug toxicity and quality of life were observed. Quality of life was scored according to twenty-two daily activity items (good,>71, fair,53< or =and<70, poor,< or =52). RESULTS: There was no significant difference in the mean age, sex, TNM stage distribution, or type of operation between the two groups (>0.05). Mean number of chemotherapy cycles was 6.5+/-3.7 (IV arm) vs 7.2+/-4.3 (Oral arm). The recurrence rate was 9/74 (12.1%) in IV arm and 6/92 (6.5%) in oral arm (P=0.937). Local recurrence was 2/74 (stage III; 2.7%) in IV arm and 1/92 (stage II; 1.1%) in oral arm. Systemic recurrence was 7/74 (Stage III; 9.4%) in IV arm and 5/92 (Stage III; 5.4%) in oral arm. Toxicity pro-files are as follows: Leukopenia (30/74, 17/92) and alopecia (21/74, 13/92) were more common in IV arm than in oral arm, and the difference was statistically significant. Diarrhea was more common in oral arm. The quality of life score was better at 1 month (19.5%, 49%) and at 2 months (47%, 72%) in the oral arm group (<0.05). CONCLUSION: Oral Doxifluridine with leucovorin as a postoperative adjuvant therapy shows a therapeutic efficacy comparable to the intravenous 5-FU regimen and has a high quality of life. The oral regimen also can be safely given with an appropriate toxicity and tolerability.
Alopecia ; Arm ; Diarrhea ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Fluorouracil* ; Humans ; Leucovorin ; Leukopenia ; Prospective Studies* ; Quality of Life ; Rectal Neoplasms* ; Recurrence

OBJECTIVE: The purpose of this study was to examine the pharmacological treatment patterns and clinical responses in inpatients and/or outpatients with obsessive compulsive disorder (OCD) at a university hospital. METHODS: A total of 71 OCD patients were included and followed during the first 4 months, first year and second year from 1998. The patterns of medication use and clinical responses according to the Yale-Brown obsessive-compulsive scale (Y-BOCS) were analyzed descriptively in this period. RESULTS: During the first 4 months, 26.7% of the patients underwent monotherapy in which most of the drugs were serotonin reuptake inhibitors (SRIs). Therapy with two or more drugs was administered in 66.6% of the patients and combination drugs with SRIs were atypical antipsychotics and clonazepam. The clinical response rate using Y-BOCS was 24.0% compared with baseline score. During the first year, the frequency of the monotherapy decreased to 6.5%, while that of therapy with two or more drugs increased to 80.6% (two and three drug frequencies were 35.3%, and 32.3%, respectively). The clinical response rate was 26.4% during this period. During the second year, the frequency of the monotherapy was 25% and that of multidrug therapy was 70.8% (two and three drug frequencies were 20.8%, and 45.8%, respectively). The clinical response rate was 39.3% compared with baseline score. CONCLUSIONS: In this study, the frequency of the combination therapy was relatively high compared with SRI monotherapy during the first 4 months and it increased further during the first year. The combination therapy was maintained without change of SRI dosage during the second year. Most of the drugs used in the combination therapy were atypical antipsychotics and clonazepam.
Antipsychotic Agents ; Clonazepam ; Drug Therapy* ; Humans ; Inpatients ; Obsessive-Compulsive Disorder* ; Outpatients ; Serotonin Uptake Inhibitors

PURPOSE: Preoperative radiation treatment with concomittant intravenous infusion of 5-fluorouracil has been known to be effective in shrinking and downstaging the tumor. Treatment with Doxifluridine (synthetic 5-deoxynucleoside derivative) medication prolongs drug exposure to tumor tissue, so it can be considered synergistic to concurrent radiotherapy. Intravenous 5-FU and oral Doxifluridine were compared with respect to tumor response, toxicity, and quality of life of patients. METHODS: Twenty eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998 were included. Intravenous 5-FU (450 mg/m2/day) and leucovorin (20 mg/m2) was given for five consecutive days during first and fifth weeks of irradiation therapy (50.4 Gy) (N=14). Oral Doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) was given daily during radiation treatment (N=14). Quality of life was scored according to twenty two activity items (good: >77, fair: >58, poor: <57). Surgical resection was performed four weeks after completion of concurrent chemoradiation treatment. Tumor response was classified as CR (Complete Response), PR (Partial Response: 50% diminution of tumor volume or downstaging), or NR (No Response). RESULTS: Tumor response was CR: 3/14 (21.4%), PR: 7/14 (50%) and NR: 4/14 (28.6%) in IV arm versus CR: 2/14 (14.2%), PR: 6/14 (42.9%) and NR: 6/14 (42.9%) in oral arm (p=0.16, 0.23, 0.24, respectively). Quality of life was poor (36.4% vs 33.3%), fair and good (63.6% vs 66.7%, respectively) between IV arm and oral arm. Systemic recurrence during follow up periods was 1/14 (7.1%) in IV arm and 2/14 (14.3%) in oral arm, respectively (p=0.307). One local recurrence was observed in oral arm. Hematologic toxicity was 3/14 (21.4%) in IV arm versus 4/14 (28.5%) in oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) versus 5/14 (35.7%) and stomatitis was observed in IV arm (1/14, 7.1%) CONCLUSION: Oral doxifluridine based chemotherapy shows a comparable tumor response and oncologic results, but there was no benefits as far as quality of life and toxicity were concerned.
Arm ; Drug Therapy ; Fluorouracil* ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Leucovorin ; Prospective Studies* ; Quality of Life ; Radiotherapy ; Rectal Neoplasms* ; Recurrence ; Stomatitis ; Tumor Burden ; Ultrasonography

OBJECTIVE: This study sought to identify candidate genes related to the clinical effects of several mood stabilizers through gene expression profiles using microarrays and real time RT-PCR. METHOD: Rats were treated with lithium carbonate, valproate, or clozapine for 10 days. Total RNA was extracted from the rat brains and used for microarray analysis. Of 54 genes showing more than 1.5-fold changes induced by all three mood stabilizers, seven genes were selected, and drug-induced changes in gene expression were confirmed by real time RT-PCR. In addition, genotype distribution of the GRIK2 gene was compared between 181 patients with bipolar disorder and 350 normal controls. RESULTS: Of the seven candidate genes, GRIK2 and PRKAR were confirmed as being downregulated by lithium and valproate. However, none of the genes was affected by all three drugs. The allele and genotype distribution in two SNPs of GRIK2 did not differ between the patient and control groups. CONCLUSIONS: Although this study demonstrated overall negative results, the present findings will be used in future studies for establishing various mechanisms of mood stabilizers.
Alleles ; Animals ; Bipolar Disorder ; Brain* ; Clozapine ; Gene Expression* ; Genotype ; Humans ; Lithium ; Lithium Carbonate ; Microarray Analysis ; Polymorphism, Single Nucleotide ; Rats* ; RNA ; Transcriptome ; Valproic Acid

OBJECTIVES: The purpose of this study was to investigate the changes of cognitive dysfunctions in patients with obsessive compulsive disorder (OCD) over the two-year of pharmacological treatment. METHODS: The thirty-three OCD patients and thirteen normal subjects were administered the neuropsychological tests and clinical evaluations twice (at the baseline and two-year). RESULTS: In spite of the two-year treatment, the accuracy of delayed recall on the Rey-Osterrieth Complex Figure Tests (RCFT), the numbers of responses on the category and letter test of Controlled Oral Word Association Test (COWA), the response time on the Trail Making Test part A (TMT-A) remained significantly impaired in the OCD patients compared with the normal controls. CONCLUSION: These findings suggest that the cognitive dysfunctions such as visuospatial memory and verbal fluency might be the underlying persisting neuropathophysiology of OCD.
Follow-Up Studies* ; Humans ; Memory ; Neuropsychological Tests ; Obsessive-Compulsive Disorder* ; Reaction Time ; Trail Making Test ; Word Association Tests