GROWTH HORMONE MODULATION OF ARGININE-INDUCED GLUCAGON RELEASE: STUDIES OF ISOLATED GROWTH HORMONE DEFICIENCY AND ACROMEGALY

Plasma glucagon and insulin responses to l -arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.     

An early gallstone clearance following repeat piezoelectric lithotripsy

Piezoelectric extracorporeal litotripsy was performed in 128 symptomatic patients with radiolucent gall-bladder stones to assess the significance of disintegration in fragment clearance. Up to 10 repeat lithotripsy sessions were scheduled to achieve a fragment target size of <3 mm. Fragmentation assessed by the size of the largest fragments after the last session was graded into three classes. I: sludge-like disintegration, 18%; II: <3 mm (mean ± s.d., 1.7 ± 0.5 mm), 56%; and III: < 3 mm (3.3 ± 0.6), 26%. All patients were initially subjected to lithotripsy alone. Bile acid dissolution therapy was started only when ultrasonography failed to show the evidence of decrease in the <3 mm fragments during a 1 month follow up. Finally, 69 patients (54%) were treated by lithotripsy alone, and the remaining 59 received additional dissolution therapy at a mean period of 2.5 months after the initial lithotripsy. The rate of complete clearance in class I, II and III patients was 91, 42 and 10% at 6 months and 100, 68 and 49% at 18 months, respectively. Significant differences were noted between the three fragmentation grades (I vs II, III, P <0.0001; II vs III, P <0.02). The patients with complete clearance within 6 months were seen only in those treated by lithotripsy alone, while the majority (87%) of patients with complete clearance during the later period were seen in those treated by additional dissolution therapy. We conclude that a high degree of fragmentation appears to lead stones to an earlier period clearance, and reduce the need for dissolution therapy.     

Sympathetic Nervous System Response to Dynamic Exercise in Complete AV Block Patients Treated with AV Synchronous Pacing with Fixed AV Delay or with Auto-AV Delay

IGAWA, O., ET AL.: Sympathetic Nervous System Response to Dynamic Exercise in Complete AV Block Patients Treated with AV Synchronous Pacing with Fixed AV Delay or with Auto-AV Delay. To investigate the sympathetic nervous system (SNS) responses and circulatory responses to exercise in eight patients (five male and three female) with complete atrioventricular block (CAVB) treated with atrio-ventricular (AV) synchronous pacing, a symptom-limited, multistaged treadmill stress test was performed, and plasma norepinephrine (NE) and circulatory parameters were measured at rest, at peak exercise, and in the recovery period. The eight patients were tested using the fixed AV interval (150 or 156 msec). Their exercise tolerance was generally poor. In all measured points, plasma NE levels were significantly higher in the eight study patients than those in the 12 normal subjects (eight male and four female). Systolic blood pressure (SBP) of CAVB patients elevated significantly after exercise compared to that at peak exercise. Heart rate (HR) responses of CAVB patients were characterized by their poor increase at peak exercise. These results suggest that some latent cardiac dysfunction continues in the CAVB patients however satisfactorily the AV synchronous pacing might perform. AV synchronous pacing with three different kinds of auto-atrioventricular delay (auto-AVD) was applied to three of the eight patients. In each AVD mode, a treadmill stress test was performed repeatedly according to the same protocol. Plasma NE concentrations under the condition with fixed AVD at peak exercise increased compared to those under the other two conditions with auto-AVD. These findings suggest that AV synchronous pacing with auto-AVD WQS better than that with fixed AVD during exercise. Plasma NE response to exercise seems to be a useful indicator for evaluating the condition of patients treated with DDD pacemakers and their adaptation for cardiac function.     

SUBCELLULAR TYROSINASE ACTIVITY IN FORTNER''S MALIGNANT MELANOMA

SUMMARY. —Biochemical and macromolecular characterizations of Fortner's melanotic melanoma of Syrian (golden) hamsters and of B-16 melanotic mouse melanoma were made using the Warburg manometric technique for estimation of the subcellular distribution of tyrosinase activity.
The results showed that the major amount of tyrosinase activity was located in the soluble fraction of Fortner's malignant melanoma. This differs from the B-16 melanoma in which the major activity was in the large granule fraction with virtual absence of activity in the soluble fraction.
Substantial increase in the tyrosinase activity of Fortner's melanoma fractions was observed after prolonged incubation. The biological significance of this delay in attaining V_max is discussed.     

Risk of Long‐Term Dual Antiplatelet Therapy Following Drug‐Eluting Stent Implantation in Octogenarians

Objectives

To evaluate the risk of long‐term dual antiplatelet therapy (DAT) following drug‐eluting stent (DES) implantation in octogenarians.

Background

DES implantation requires DAT; however, DAT‐associated risk in octogenarians remains unclear.

Methods

Two‐hundred and six consecutive octogenarians (130 men, 83.3 ± 3.4 years) underwent stent implantation (104 bare metal stents [BMSs] and 102 DESs) and 38.0 ± 13.2 months of follow‐up.

Results

Significantly more DES patients received DAT. The incidence of bleeding events was similar in the DES and BMS groups for 1 year (total: 10.8% vs 5.8%, P = 0.19; major: 4.9% vs 2.9%, P = 0.70). However, after 2 years, significantly more bleeding events occurred in the DES group than the BMS group (total: 2 years, 21.6% vs 9.6%, P = 0.02; 3 years, 29.4% vs 11.5%, P = 0.001; 4 years, 31.4% vs 15.4%, P = 0.007; major: 2 years, 12.7% vs 3.8%, P = 0.04; 3 years, 18.6% vs 5.8%, P = 0.005; 4 years, 19.6% vs 6.7%, P = 0.006). Overall, significantly more total bleeding events (31.4% vs 15.4%, P = 0.007) and major bleeding events (19.2% vs 6.7%, P = 0.006) were observed in the DES group than in the BMS group. The adjusted hazard ratios and 95% confidence intervals (CI) were as follows: total bleeding events, 2.203 (95% CI: 1.065–4.556; P = 0.033); major bleeding events, 4.324 (1.506–12.414; P = 0.007).

Conclusions

DAT was associated with an increased risk of bleeding events in octogenarians after 2 years. DAT discontinuation should be considered for octogenarians 1‐year post‐DES implantation. (J Interven Cardiol 2013;26:114–122)

     

Recent Perspective on Coronary Bifurcation Intervention: Statement of the “Bifurcation Club in KOKURA”

The treatment of coronary bifurcation lesion remains a challenging issue even in the drug‐eluting stent era. Frequent restenosis and stent thrombosis have been recently shown to be related not only to geometrical gap or stent structural deformation but also to rheological disturbance. Low wall shear stress at the lateral side of the bifurcation is likely to cause atherosclerotic changes due to easy access of the macrophages that induce chemical mediators. The turbulent flow over stent metal may facilitate accumulation of platelets, which results in thrombosis. The jailed strut and excess metal overlap may increase these risks. Since dramatic changes of the coronary flow pattern at the bifurcation are closely related to the genesis of atherosclerosis, future bifurcation intervention technique should be considered to restore the original physiological state as well as the anatomical structure. This article summarizes the global consensus of the members of the Asian Bifurcation Club and European Bifurcation Club at the KOKURA meeting. It also provides a perspective of basic sciences relating to bifurcation anatomy, physiology, and pathology, in the search for a best strategy for bifurcation intervention. (J Interven Cardiol 2010;23:295–304)     

Clinical Study of Cyclocytidine in Children With Acute Leukemia

One hundred children with various types of leukemia were given113 treatments with cyclocytidine. Eighty-four of these patientshad been treated previously. Cyclocytidine was daily given intravenouslyfor four to 11 consecutive days in amounts of 20mg/kg or 500mg/m².The treatment course . was repeated, when necessary. Complete remission was obtained in one case of monocytic leukemiaamong six treated by cyclocytidine alone. Combined therapy withsteroid hormone gave 14 complete and eight partial remissionsin 38 cases, the remission rate standing at 58%. There were30 complete and 16 partial remissions in 69 cases treated withcombination therapy with two or more agents, and the remissionrate was 67%. Transient pains in the region of the parotid gland were themost characteristic toxicity. GI tract symptoms were less commonand milder than those of cytosine arabinoside. Dizziness wasnoticed in three cases. Nine children with acute leukemia who were given cyclocytidineorally showed no remarkable response. Cyclocytidine, given parenterally, seems beneficial for varioustypes of leukemia in children.     

Association of Humps on Monophasic Action Potentials and ST-T Alternans in a Patient with Romano-Ward Syndrome

A case of Romano-Ward syndrome had episodes of torsade de pointes preceded by ST-T alternans. ST-T alternans was induced by isoproterenol and abolished by verapamil, lidocaine, mexiletine and MgSO4. A monophasic action potential (MAP) showed humps in MAPs at the right ventricular outflow tract but not at the right ventricular apex in alternate beats. Differences in the MAP duration were noted between the two areas and were associated with ST-T alternans. Atrial pacing abolished both humps and ST-T alternans. These results suggest that humps are a possible reflection of early afterdepolarizations and their appearance is limited to localized regions of the ventricles, which produces regional disparity of repolarization and ST-T alternans.     

Adrenocorticotropin-independent macronodular adrenal hyperplasia treated by simultaneous bilateral laparoscopic adrenalectomy

A 61-year-old woman was admitted to our hospital with hypertension and diabetes mellitus, and was found to have Cushing's syndrome. Radiological and endocrinological findings suggested adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. Simultaneous bilateral laparoscopic adrenalectomy was performed, minimizing the number of trocar sites and operation time. Success was attributed to the careful selection of trocar sites to permit safe dissection.     

Prominent induction of cyclin B1 in G2/M renal cancer cells with butyrolactone 1

BACKGROUND: Butyrolactone 1 (BL) is a cyclin dependent kinase (CDK) inhibitor derived from Aspergillus terreus. None of the present drugs are effective for the treatment of renal cell carcinoma. The use of BL is expected to promote a new type therapy of renal cancer. METHODS: We investigated three human renal cancer cell lines: ACHN, OS-RC-2 and RCC10RGB, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and two-color flow cytometry. Simultaneous measurements of DNA content and cyclin expression allowed us to perform cell cycle specific analysis. Western blot analysis was performed using ACHN to represent cell lines. RESULTS: BL inhibited cell proliferation and caused cell accumulation at G2/M phase associated with the emergence of the third peak. Moreover, BL induced cyclin B1 over-expression in G2/M cells. These changes were quite definite, whereas cyclins D1, E and A showed no changes at all. Cyclin B1 accumulation was confirmed by western blot analysis. The chronological observation revealed that the emergence of the third peak preceded the regression of the increased cyclin B1 positive G2/M cells. These results suggested that BL accelerated cyclin B1 accumulation in G2/M cells, which then shifted to G1 phase without cell division. New G1 cells started DNA synthesis most likely as endoreduplication to form the third peak and the mechanism of cyclin B1 accumulation converted into down-regulation. CONCLUSION: BL induced significant cell kinetic interference in the tested human renal carcinoma cell lines. This might indicate the possibility of a new medical treatment modality for renal cancer.