Value and limitations of Holter monitoring and electrophysiologic testing in the evaluation of the treatment of sustained monomorphic ventricular tachycardia

The authors studied the value and limitations of Holter monitoring and electrophysiological investigation in the evaluation of treatment of sustained monomorphic ventricular tachycardia (VT). One hundred and twenty-four consecutive patients were included in the study from January 1981 to February 1988. The etiologies were chronic myocardial infarction (N = 54), dilated cardiomyopathy (N = 24), right ventricular dysplasia (N = 31), and idiopathic VT (N = 15). All the tachycardias could be induced during baseline electrophysiological investigations and presented as complex ventricular arrhythmias on the Holter recordings. The investigations were repeated after treatment which was maintained irrespective of the results, unless the tachycardia which was induced or recorded was over 130 cycles/min and/or poorly tolerated. Recurrence was defined as the recording of VT in the absence of a change of treatment and/or the occurrence of sudden death. The follow-up period averaged 29 +/- 21 months. The Kaplan-Meier method was used to study the prevalence of absence of recurrence and survival rates. We observed 28 recurrences of VT and there were 21 deaths. Eighty-five per cent of patients had normal Holter monitoring after treatment. The prevalence of absence of recurrence was 0.751 when the Holter was normal and 0.485 when an arrhythmia was recorded (p = 0.03). The sensitivity was 25 per cent and the specificity 88 per cent. The survival rates were 0.66 and 0.585 respectively (p = 0.008). Fifty-three per cent of patients remained inducible after treatment with a prevalence of absence of recurrence of 0.572. This value rose to 0.877 when VT could not be induced (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Epac signaling is required for hippocampus-dependent memory retrieval

Previously we uncovered a critical role for norepinephrine and β₁-adrenergic signaling in hippocampus-dependent memory retrieval. Because the β₁ receptor couples to G_s, we examine here whether cAMP is also required for contextual memory retrieval. Using pharmacologic and genetic approaches to manipulate cAMP and downstream signaling, we demonstrate that cAMP and two of its targets, protein kinase A (PKA) and exchange protein activated by cAMP (Epac), are both required for retrieval. These findings demonstrate that cAMP signaling through Epac (as well as PKA) plays an essential role in cognition.     

Safety of cardiac catheterization via peripheral vascular grafts

There are few data concerning the complications and technical difficulties encountered when cardiac catheterization is performed using peripheral bypass grafts for vascular access. All cardiac catheterizations performed at our institution from January 1, 1984 to April 1, 1991 were retrospectively reviewed to assess the in-hospital clinical outcomes in patients who had arterial access for catheterization achieved via prosthetic graft puncture. Seventeen procedures had percutaneous puncture of a vascular graft from a total of 2,929 arterial catheterizations performed. The interval from graft placement to catheterization was 7.5 ± 1.1 years. Arterial sheaths were employed in all cases and corresponded to the catheter size, with 5F systems used in 53% and 7F or larger systems used in the remaining patients. No intraprocedural or postprocedural complications were recognized. Technical difficulties were limited to the inability to selectively cannulate a nondominant right coronary artery in 1 patient. We conclude that percutaneous introduction of an arterial sheath and left heart catheterization via remotely implanted vascular bypass grafts is not associated with an increased risk of procedural complications or technical difficulties. © 1993 Wiley-Liss, Inc.     

3alpha-Hydroxysteroid dehydrogenase type III deficiency: a novel mechanism for hirsutism

CONTEXT: Dihydrotestosterone (DHT), the primary active androgen in peripheral target tissues, is metabolized by 3alpha-hydroxysteroid dehydrogenase type III (3alpha-HSD), encoded by the AKR1C2 gene, forming 5alpha-androstane-3alpha,17beta-diol (3alpha-diol). 3alpha-HSD may play a role in the pathogenesis of hirsutism. OBJECTIVES: Our objective was to evaluate the role of 3alpha-HSD in hirsutism by comparing 1) tissue levels of active androgens, 2) relative gene expression of AKR1C2, and 3) activity of 3alpha-HSD in genital skin from normal and hirsute women. DESIGN: Genital skin was obtained from normal and hirsute women. After homogenization, testosterone (T) and DHT levels were quantified by conventional RIA. From isolated RNA, relative expression of AKR1C2 was determined by real-time PCR. In addition, minced genital skin was incubated with [(3)H]DHT, and the product, [(3)H]3alpha-diol, was quantified by radio-HPLC. SETTING: The study took place at an inner-city hospital. Patients: Patients included women undergoing posterior colporrhaphy. MAIN OUTCOME MEASURES: We assessed 1) tissue levels of T, DHT, and 3alpha-diol; 2) relative expression of AKR1C2; and 3) conversion ratio of [(3)H]3alpha-diol to [(3)H]DHT. Results: In genital skin, tissue DHT and T concentrations in hirsute women were 1.90-fold and 1.84-fold higher than in normal women (P =0 .002 and 0.03), and relative expression of AKR1C2 mRNA was reduced approximately 7-fold (P = 0.04). Genital skin from hirsute women showed less metabolism of [(3)H]DHT to [(3)H]3alpha-diol (conversion ratio, 0.24 +/- 0.19 vs. 0.85 +/- 0.55, P = 0.01). CONCLUSIONS: In genital skin of hirsute women, reduced AKR1C2 gene expression and 3alpha-HSD activity results in decreased DHT metabolism and elevated tissue levels of DHT. Diminished DHT metabolism may play an important role in the pathogenesis of hirsutism.     

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.     

Influence of nifedipine on left ventricular systolic and diastolic function: Relationships to manifestations of ischemia and congestive failure

In addition to the favorable effects of calcium antagonists on symptoms related to coronary spasm, we recently documented preclusion of ergonovine-induced coronary spasm angiographically in four patients with proved Prinzmetal's angina.To determine whether nifedipine has similar “relaxing” or negative inotropic actions on left ventricular myocardial function, we studied 19 patients with various degrees of left ventricular dysfunction before and after nifedipine (20 mg sublingually) during cardiac catheterization. Left ventricular afterload was reduced, with a significant (13 percent) decline in arterial pressure; left ventricular diastolic pressures were unchanged. Left ventricular ejection function was augmented, with significant increases in ejection fraction (14 percent), mean velocity of circumferential fiber shortening (41 percent), systolic ejection rate (25 percent), and end-systolic $\text{pressure}\text{volume}$ ratio (19 percent). Cardiac index increased significantly by 16 percent. Early diastolic relaxation, diastolic pressure-volume relations and end diastolic stiffness remained unchanged after nifedipine. When patients were categorized (Group I: left ventricular end-diastolic volume ≤ 90 ml/m², end-diastolic pressure ≤ 20 mm Hg; Group II: end-diastolic volume > 90 ml/m², end-diastolic pressure > 20 mm Hg), highly pertinent differences were apparent. Nifedipine significantly reduced left ventricular preload and end-diastolic pressures in Group II but not in Group I patients. Enhancement of left ventricular ejection function in Group II patients was significantly more prominent than that in patients with normal baseline function. Although diastolic properties were insignificantly changed overall, the left ventricular diastolic pressure-volume relation was displaced downward by nifedipine in Group II, but not in Group I patients. Both systemic and pulmonary vascular resistance declined significantly more in Group II patients, whereas cardiac index was increased 25 percent compared with a negligible change in group I patients. These results indicate beneficial effects of nifedipine on myocardial oxygen requirements, particularly in patients with impaired left ventricular function in whom left ventricular preload and afterload were both significantly reduced, cardiac index augmented and the pressure-volume relation shifted downward.To confirm predicted symptomatic benefits in 13 other patients with fixed coronary, disease, incremental atrial pacing to anginal threshold was performed before and 30 minutes after nifedipine (20 mg sublingually). Mean paced heart rate at onset of angina increased 19.3 percent after nifedipine. Concomitantly, aortic pressure decreased significantly by 22.1 percent at the onset of angina; double product was unchanged at the anginal threshold. Thus, although left ventricular afterload was reduced by nifedipine, the anginal threshold was unchanged in terms of myocardial oxygen requirements.In concert, these results indicate that therapeutically effective influences of nifedipine in patients with fixed coronary disease are attributable basically to hemodynamic alterations consequent upon left ventricular afterload reduction. Nevertheless, such effects imply therapeutic benefit, the reduced afterload concomitantly permitting greater exercise-induced tachycardia before the anginal threshold is reached.     

The metabolism of gonadotropin in goldfish, Carassius auratus: Tissue uptake and distribution during the reproductive cycle

The time course of gonadal uptake of intraarterially injected radioiodinated carp glycoprotein gonadotropin (¹²⁵I-cGtH) was determined in goldfish maintained at 12 ± 1 or 20 ± 1°, during different stages of the annual reproductive cycle. The results indicated that elevated temperature could alter the pattern of uptake in goldfish undergoing ovarian recrudescence but not in sexually regressed female goldfish. Also when changes in the ovarian surface area to volume ratio are accounted for, the amount of ¹²⁵I-cGtH incorporated into the ovary on a per-unit-weight basis, is much greater in sexually maturing and mature female goldfish compared to sexually regressed fish. The tissue distribution of trichloroacetic acid-precipitated ¹²⁵I-cGtH determined in sexually regressed male and female goldfish; 15 min after injection, indicated that the kidney provided the greatest concentration of tissue-specific activity. In contrast, the gonads of sexually regressed goldfish accumulated a relatively small amount of ¹²⁵I-cGtH in terms of both tissue-specific activity and whole-organ accumulation. The possible roles of the gonad in ovarian recrudescence are discussed in relation to recent information concerning both the pituitary gland secretion and plasma metabolic clearance rate of gonadotropin.     

Cocaine, not morphine, causes the generation of reactive oxygen species and activation of NF-κB in transiently cotransfected heart cells

This study was designed to determine levels of NF-κB reporter gene activity and free radical generation in cultured striated myocytes (H9C2 cells) exposed to cocaine or morphine in the presence of free radical scavengers. Cells were transiently transfected with a NF-κB reporter gene and changes in luciferase activity were detected, by bioluminescence. Using confocal microscopy and 2′,7′-dichlorofluorescin diacetate, cocaine-induced or morphine-induced free radicals were quantified in H9C2 cells. Cocaine and morphine (0–1×10⁻² M) were tested separately. Cocaine but not morphine significantly activated Nf-κB reporter gene, activity in H9C2 cells. Overexpression of IκB inhibited NF-κB reporter activity at low (1×10⁻⁴ M) but not high (1×10⁻² M) cocaine concentrations. Free radicals were generated in H9C2 cells stimulated with cocaine but not with morphine. The production of free radicals and NF-κB reporter gene activity could be blocked with N-acetylcysteine, glutathione, and to a lesser extent, lipoic acid. The results suggest that cocaine induces free radical production, which leads to the activation of NF-κB signal transduction and possible inflammatory responses.