Effects of L-carnitine on exercise tolerance in patients with stable angina pectoris

The effects of L-carnitine (900 mg, p.o. daily) on exercise performance were studied in 12 patients with stable effort angina using a multistage treadmill exercise test. Exercise tests were performed at the end of the placebo period and after 4 and 12 weeks of carnitine therapy. While 12 patients experienced angina during treadmill tests in the placebo period, 2 patients were free of angina after treatment with carnitine. The mean exercise time was 11.4 +/- 0.7 min (mean +/- SE) in the placebo period. This increased significantly to 12.2 +/- 0.5 min (p less than 0.05) after 4 weeks and 12.8 +/- 0.5 min (p less than 0.01) after 12 weeks of treatment with carnitine. The time required for 1 mm ST depression to occur was 6.4 +/- 0.9 min in the placebo period. This increased significantly to 7.6 +/- 0.9 min (p less than 0.01) after 4 weeks and 8.8 +/- 1.0 min after 12 weeks of treatment with carnitine. There was significantly less ST segment depression during the same exercise load after 12 weeks of treatment as compared with that in the placebo period (p less than 0.05). The heart rate and the pressure rate product at the same work load showed no significant difference among the 3 testing periods. The results of this study suggest that L-carnitine may improve exercise tolerance in patients with effort angina.     

Venous pressure and compliance of the peripheral capacitance vessels.

Compliances of the peripheral capacitance vessels decreased gradually in accordance with the increase in pressure of the brachial vein. The relationship between them formed a number of hyperbolic-like curves, the same results as those found in many cases of both normal subjects and patients with congestive heart failure. The decrease of compliance of the peripheral capacitance vessels was not the result of an organic change, but of a functional change of the vessels caused by distention.     

A clinical study of bacteremia in the last fifteen years]

Between 1976 and 1990, 208 cases of bacteremia in our department were studied. Community acquired bacteremias were only 18 (8.7%) cases. Bacteremias, particularly caused by Gram positive organisms, increased significantly after 1981, compared with the first five years. It was related to the marked increase in cases of venous access devices and less sensitivity of the Gram positive organisms to the new cephem antibiotics. In the study, 144 (69.2%) cases were eradicated. Severe underlying diseases or complication of pneumonia influenced the eradication rate of bacteremia. Bacteremia caused by methicillin resistant Staphylococcus aureus or Pseudomonas aeruginosa showed poor prognosis. The average duration from onset to death, was 5.1 days. Forty cases (62.5%) died within 3 days. Among the 201 cases, leukocytosis (WBC greater than 10,000/mm3) was present in 38.3%, while leukopenia (WBC less than 1000/mm3) in 25.3%. Eradication rate between the two groups was not significant. CRP was elevated (greater than 8.5 mg/dl) in 63.5%. The prognosis of this group was significantly poor. Elevation of serum bilirubin was also related with increase of mortality. According to these results, empiric therapy before the isolation of organisms is the most important strategy for treatment of bacteremia.     

Electrophysiological and pharmacological studies on the mechanisms of ventricular tachycardia

Employing electrophysiological and pharmacological methods, the mechanisms of recurrent ventricular tachycardia were studied in 31 patients, 18 with old myocardial infarction and 13 with idiopathic ventricular tachycardia. In the cases of ventricular tachycardia with old myocardial infraction, the initiation and termination of the tachycardia could be achieved by programmed electrical stimulation in 13 out of 18 patients. Endocardial mapping showed that the earliest excitation site during tachycardia was at the border zone of infarction, where the diastolic fragmented activity was detected. Programmed electrical stimulation sometimes provoked more than two kinds of QRS morphology of tachycardia in the same patient. Class IA antiarrhythmic agents were effective in terminating tachycardia. These data suggest that there are multiple reentrant pathways consisting of partially depressed fast fibers at the border zone of infarction. In the cases with idiopathic ventricular tachycardia, the induction and termination of tachycardia was effected by electrical stimulation in 8 out of 13 patients. For the termination of tachycardia, long overdrive pacing was sometimes necessary. The diastolic fragmented activity could not be detected by endocardial mapping. A class IV drug such as verapamil was more effective for the termination of tachycardia than class I drugs, and there were repetitive short runs of ventricular extrasystole observed until the final termination. These data support the reentrant pathways containing slow with enhanced automaticity as the circuit of idiopathic ventricular tachycardia.     

Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase

Myeloperoxidase (MPO), which is located within neutrophils capable of producing hypochlorous acid, is active in vitro against bacteria and fungi. However, MPO-deficient persons are usually healthy. To define the in vivo contribution of MPO to early host defense against pulmonary infections, MPO-deficient and control mice were intranasally infected with various fungi and bacteria, and the number of residual microorganisms in lungs was compared 48 h later. MPO-deficient mice showed severely reduced cytotoxicity to Candida albicans, Candida tropicalis, Trichosporon asahii, and Pseudomonas aeruginosa. However, the mutant mice showed a slight but significantly delayed clearance of Aspergillus fumigatus and Klebsiella pneumoniae and had comparable levels of resistance to the wild type against Candida glabrata, Cryptococcus neoformans, Staphylococcus aureus, and Streptococcus pneumoniae. These results suggest that the MPO-dependent oxidative system is important for host defense against fungi and bacteria, although the effect varies by pathogen species.     

Molecular genetic approaches to Mycobacterium tuberculosis

Recent progress of molecular genetics has been providing tools for new approaches to disease treatment and diagnosis of Mycobacterium tuberculosis. In 1998, Cole et al. reported the complete genome sequence of Mycobacterium tuberculosis. The new information will provide us the knowledge and understanding of the biology of Mycobacterium tuberculosis. Further, it will provide us new conception of diagnosis and treatment of the disease. Four topics were selected in this symposium. Dr. Iinuma reviewed and prospected the clinical utility of nucleic acid amplification methods of Mycobacterium tuberculosis. Dr. Suzuki reviewed the molecular mechanism of acquired resistance to anti-TB drugs and reported the early detection of genetic mutation by new designed DNA tip method. Dr. Takahashi reviewed the method of molecular epidemiology and genetic elements as a tool for strain differentiation of tuberculosis. Dr. Mizuguchi interpreted the essential feature of mycobacterial genome maps, and genes and their biological activity. He also reviewed the importance and the utility of the complete genome sequence of tuberculosis in association with pathogenecity. These topics were summarized in this report, based on the symposium of "Molecular genetic approaches to Mycobacterium tuberculosis" in the 75th annual meeting of the Japanese Society for Tuberculosis.     

Prognostic significance of time-delay to peak creatine kinase after direct percutaneous coronary intervention in acute myocardial infarction patients

The aim of the present study was to investigate the prognostic significance of time-delay to peak creatine kinase (CK) after successful direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Our 240 consecutive first AMI attack subjects admitted within 5 hours from onset were successfully reperfused by direct PCI therapy. Subjects were divided into two groups according to the upper quartile value of peak-CK time from onset, the early peak-CK group (peak-CK time < or = 16 hours from onset, n = 180) and the late peak-CK group (peak-CK time > 16 hours, n = 60). (I) The early ST-segment resolution rate was lower in the late peak-CK group compared with the early peak-CK group (P < 0.05), and there were significantly fewer patients with preinfarction angina pectoris in the late peak-CK group than in the early peak-CK group (P < 0.01). (II) LVEF in the chronic stage was significantly lower in the late peak-CK group than in the early peak-CK group (49 +/- 13% versus 57 +/- 13%, P < 0.001). (III) There were significantly more patients with major complications in the late peak-CK group than in the early peak-CK group (required CABG: 10% versus 3%, P < 0.05; cardiac death: 18% versus 3%, P = 0.0001). (IV) Multivariate analysis identified late peak-CK as an independent predictor of cardiac death (Odds ratio 7.91, 95% C.I. 1.40-44.11, P < 0.05). In patients with AMI, the time-delay to peak-CK after successful direct PCI may be closely related to left-ventricular systolic dysfunction and poor patient outcome, including mortality.     

Clinical effects of nitrendipine on variant angina pectoris

The clinical effects of nitrendipine, a new calcium antagonist, were investigated in a single-blind test on 21 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during different treatment periods at doses of 10 mg once a day (period I) and 20 mg once a day (period II). The number of anginal attacks decreased significantly from a pretreatment level of 2.1 +/- 0.3 per day to 0.7 +/- 0.2 per day in treatment period I and 0.3 +/- 0.1 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with the observation period before treatment (p less than 0.01, p less than 0.001, respectively). In 20 patients with continuous ECG monitoring, the frequency of ST-segment elevation was 4.5 +/- 1.0 per day during the pretreatment period; it decreased significantly to 0.9 +/- 0.6 per day in treatment period I and 0.5 +/- 0.3 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The duration and the maximum magnitude of ST-segment elevation also improved significantly in both treatment periods. These results demonstrate the efficacy of nitrendipine in the treatment of variant angina at a single daily dose of 10 mg.     

Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations

BACKGROUND: Recurrence is frequent after piecemeal snare resection of large sessile colorectal polyps. The aim of this study was to evaluate the safety and efficacy of argon plasma coagulation (APC) in preventing recurrence when applied to the edge and base of the polypectomy site after apparently complete piecemeal resection. METHODS: Patients with large (>1.5 cm) sessile polyps removed by piecemeal snare cautery were placed into 2 groups. The first consisted of patients with polyps believed by the endoscopist to be completely excised. These patients were randomized to either no further therapy (control) or to APC of the rim and any residual mucosal or submucosal tissue in the base of the polypectomy site. The second group comprised patients in whom polyps, as judged by the endoscopist, were incompletely excised by snare polypectomy; APC was routinely applied without randomization to all visible remaining adenomatous tissue. Follow-up colonoscopy was performed within 3 months and 1 year; biopsy specimens were taken routinely from the resection site and further polypectomy was performed as indicated. RESULTS: There were fewer recurrences after APC in the randomized group (1/10 APC, 7/11 no APC; p = 0.02). In the group with initial incomplete snare polypectomy, recurrence was detected at 3 months in 6 of 13 despite APC. One patient was hospitalized with abdominal pain and minor rectal bleeding but required no intervention. There were no other episodes of significant late bleeding caused by piecemeal polypectomy. One patient was referred for surgery after unsuccessful endoscopic management. CONCLUSIONS: In patients with apparent complete endoscopic snare resection of large adenomas, postpolypectomy application of APC reduces adenomatous recurrence.