Detection of Pyrazinamide Resisitance in Mycobacterium Tuberculosis by Sequencing of pncA Gene / 결핵

BACKGROUND: Examining the biological susceptibility of Mycobacterium tuberculosis to pyrazinamide (PZA) in vitro is very difficult as PZA is inactive under normal culture conditions. The susceptibility test, an enzyme assay for Pzase activity, and a genetic test for pncA gene mutations, were performed in order to predict PZA resistance. METHODS: 28 cultured clinical isolates of Mycobacterium tuberculosis were tested. The biological susceptibility was performed by the absolute concentration method using Lowenstein-Jensen media. The PZase activity was tested by means of Wayne's method. A 710-bp region includes the entire open reading frame of pncA was amplified and sequenced. RESULTS: All six strains with positive PZase activity exhibited no pncA mutations with one strain showing a false resistance in the biological susceptibility test. Among the 22 strains with no PZase activity, 21 exhibited showed pncA mutations. In the biological suscaptibility test, 20 strains were resistant, and one was susceptible, and the other failed to test. The mutation types varied with ten missense, one silent and one nonsense mutation 1 slipped-strand mispairing, and 6 frameshift mutations. Three strains had an adenine to guanine mutation at position - 11 upstream of the start codon. CONCLUSION: The mutation at the pncA promotor region is frequent at -11 upstream position. Automatic sequencing of pncA is a useful tool for rapid and accurate detection of PZA resistant M.tuberculosis, and for demonstrating the epidemiological relatedness of the PZA-resistant M.tubersulosis strains.

Evaluation of the Efficacy and Tolerability of Isradipine in the Treatment of Mild to Moderate Hypertension

An open clinical trial was conducted to evaluate the efficacy and tolerability of isradipine in 30 cases (male 16, female 14 cases, average age 52.6+/-7.94) of mild to moderate essential hypertension using 1.25-2.5mg twice a day for 8 weeks of active treatment. Blood pressure was significantly reduced from 168.5+/-14.33/108.3+/-6.37mmHg, 163.7+/-9.74/105.5+/-7.1mmHg to 141.0+/-13.69/92.0+/-9.27mmHg, 138.8+/-13.46/92.3+/-11.16mmHg in sitting and standing position respectively. The extent of reduction was 27.5/16.3mmHg in sitting position and 29.9/13.2mmHg in standing position. This comprised the mean response rate in terms of reduction of DBP of 10mmHg or more being 90% and the normalization rate, deficed as DBP lowering to 90mmHg or below, being 70%. Heart rate, hematology and blood chemistry including blood sugar and lipids were not changed significantly after treatment with isradipine. No significantl side effect was observed except 2 cases of mild transient facial flushing and nausea during the treatment, so could proceed the trial without drug discontinuation in all 30 cases. The results suggest that isradipine is one of the useful and safe drugs in the treatment of mild to moderate essential hypertension.

Clinical Evaluation on Serial Changes of Serum Immunoglobulin E in Patients with Acute Myocardial Infarction

Serial changes of serum IgE, IgG, eosinophils were observed in 25 patients with acute myocaridial infarction and 20 ischemic heart disease without evidence of acute myocardial infarction and evaluated in terms of several parameters and its clinical significance. The results observed were as follows : 1) Serum IgE levels were propgressively elevated from the first hospital day(259+/-3IU/ml) up to peak level of the fifth hospital day(415+/-2IU/ml) and progressively lowered and returned to almost same level as the first hospital day on the twenty first hospital day. On the other hand control group showed significantly lower IgE levels throughout all hospital day and also did not showed serial change. 2) In the patient group with the initial serum IgE level above 200IU/m; showed significantly lower level of serum SGOT, CPK level than the group of below 200IU/ml group. This suggests the initial serum IgE level might have some correlation of the extent of myocardial necrosis. 3) In patients of acute myocardial infarction, ejection fraction was checked at discharge. Initial serum IgE level above 200IU/ml group showed significantly higher ejection fraction than below 200IU/ml group(59.4+/-13.5% vs 38.4+/-13.7%). 4) Serum IgE was checked concomittantly with serum IgE. It showed slightly decreasing tendency at third hospital day but not statistically significant. Eosinophil changed similar pattern as serum IgE but it was also not statistically significant. In conclusion, serial checking of serum IgE level in patient of acute myocardial infarction may give some help in prediction the clinical course and prognosis.

Clinical Effects of Isosorbide 5-Mononitrate(Elantan(R)) on Angina Pectoris

An open trial was carried out to investigate the efficacy and tolerance of isosorbide 5-mononitrate(Elantan(R)) in 30 patients diagnosed as angina pectoris at Pusan national university hospital. Drugs were given 20mg two times daily for 2 to 3 weeks and the results were assessed in terms of effects on anginal pain and untoward side effects experienced during administration of medication. Treament resulted in an overall improvement in 25 patients(83.4%), complete abolition of anginal attacks in 17 patients(56.7%) and reduction in frequency of attacks in 8 patients(26.7%). So called "Nitrated headache" was observed in 5 patients(16.6%) but improved with proceeding of administration in 3 patients. This trial indicates that isosorbide 5-mononitrate should be efficacious as well as tolerated in patients with coronary heart disease.