Allogeneic Bone Marrow Transplantation for the Treatment of Acute Leukemia: The Kanazawa Experience

Twelve patients with acute leukemia (7 with nonlymphoblasticleukemia and 5 with lymphoblastic leukemia) were treated withhigh-dose cyclophosphamide and 1,000 rad total body irradiationfollowed by allogeneic bone marrow transplantation from theirHLA-identical sibling donors. Of eight patients given transplantsat relapse, only one patient has become a long-term survivor;he is alive in disease-free complete remission (CR) 4 yr afterthe transplantation. A cure is probable in this patient. Offour patients given transplants during remission, two have survivedin unmaintained CR for almost 1 yr or more. Recurrent leukemiawas observed in two patients whose disease was resistant toconventional therapy at the time of transplantation. Major causesof treatment failure were interstitial pneumonia, hepatic failuredue to veno-occlusive disease, severe infection and relapse.Transplantation-related complications were more frequent andserious in patients who received transplants at relapse thanin those receiving them during remission. The incidence of graft-versus-hostdisease was relatively high but the disease was neither primarynor leading cause of death. These preliminary but relativelyencouraging data suggest that transplantation during remissionmay reduce posttransplant morbidity and mortality. This approachwill contribute to producing long-term survival or cure in patientswith adult acute leukemia if a suitable donor is available.     

EFFECT OF PROPRANOLOL ON THE VENTRICULAR ARRHYTHMIAS INDUCED BY HYPERCARBIA DURING HALOTHANE ANAESTHESIA IN MAN

The effects of propranolol on arterial blood pressure, heartrate, and cardiac rhythm during ventricular arrhythmias initiatedby hypercarbia were investigated in thirteen subjects during1 per cent halothane anaesthesia. Propranolol was consistentlyeffective in the treatment of ventricular arrhythmia inducedby hypercarbia in all subjects. The successful use of propranololsuggests that the mechanism for ventricular arrhythmia producedby respiratory acidosis during halothane anaesthesia was relatedto beta adrenergic receptors. Blockade of these receptors bybeta adrenergic agents decreased markedly the sensitizationof myocardium to sympathetic stimulation.     

BIPHASIC EFFECTS OF ALCOHOL DRINKING ON METHAMPHETAMINE METABOLISM IN MAN

In methamphetamine (MAP) addicts, long-term ethanol ingestion3–4 times per week induced an increased rate of p-hydroxylationof MAP and amphetamine (AMP). Simultaneous ingestion of ethanoland MAP inhibited both p-hydroxylation of MAP and AMP and N-demethylationof MAP in inebriated addicts. The p-hydroxylation of MAP andAMP was also significantly inhibited in daily drinkers despitethe almost total absence of urinary ethanol. This suggests thatthe intensity of MAP-induced behavioral and psychological effectsin MAP addicts may, in part, depend upon their drinking habits.     

IMMUNOHISTOCHEMICAL STUDY OF OVEREXPRESSION OF FIBROBLAST GROWTH FACTOR-1 (FGF-1), FGF-2, AND FGF RECEPTOR-1 IN HUMAN MALIGNANT SALIVARY GLAND TUMOURS

Fibroblast growth factor-1 (FGF-1) and FGF-2 are broad spectrum mitogens. The expression of FGF-1, FGF-2, and their receptor, FGF receptor-1 (FGFR-1), was examined in malignant salivary gland tumours and normal salivary glands, using immunohistochemical methods. In seven cases of adenoid cystic carcinoma (ACC), both duct-like cells and modified myoepithelial cells were apparently immunopositive for FGF-1, FGF-2, and FGFR-1. In five cases of mucoepidermoid carcinoma (MC), all three types of tumour cells including epidermoid cells, mucous cells, and intermediate cells expressed immunoreactive FGF-1, FGF-2, and FGFR-1. In these malignant salivary gland tumours, increased expression of FGFR-1 correlated with the intensity of both FGF-1 and FGF-2 immunoreactivity. In contrast to malignant salivary gland tumours, eight cases of normal salivary gland showed negative immunostaining for FGF-1, FGF-2, and FGFR-1 while four cases were weakly immunoreactive for FGF and its receptor. These results demonstrate that malignant salivary gland tumours overexpress FGF-1, FGF-2, and FGFR-1 compared with normal salivary glands and suggest that these growth factors may play an important role in facilitating neoplastic progression in human salivary glands.     

Choice of treatments for small hepatocellular carcinoma: Hepatectomy, embolization or ethanol injection

The results of hepatectomy, percutaneous ethanol injection therapy and transcatheter arterial embolization for small hepatocellular carcinoma (HCC) of 3 cm or less in diameter from the published literature were compared with the authors' experiences with surgical treatment. The survival rates for those treated by hepatectomy and ethanol injection were almost the same, being more than 90% at 1 year and 70% at 3 years. The overall results achieved by embolization were inferior to those achieved by the other two therapeutic modalities, although the 1 year survival rate was not worse. The cancer-free survival rates after hepatectomy and ethanol injection were also similar. Most of the patients with small HCC had associated liver cirrhosis or chronic active hepatitis, but the degree of liver dysfunction and the level of hepatic reserve varied. Anatomically, the number, size, and location of the cancer also varies. Choice of treatment for small HCC should be made based upon the degree of liver function and the anatomic status of the cancer. For example, a patient with multiple (more than four) cancer nodules is a good candidate for embolization. Ethanol injection is indicated for a small HCC, deeply seated in a severely diseased liver. Hepatectomy is the first choice for a small HCC situated near the surface of a liver with relatively good liver function.     

Endoscopic Diagnosis and Treatment of Local Residual/Recurrent Lesions after Endoscopic Mucosal Resection for Early Colorectal Carcinoma

Local residual/recurrent lesions have been observed with some frequency after endoscopic mucosal resection (EMR) for colorectal tumors. Many reports have revealed that the rate of recurrence after piecemeal resection is higher than that after en bloc resection. Thus, to accomplish an appropriate trimming in EMR, it is important to closely observe the lesions to be resected, possibly by magnification. Our data show that, with careful trimming of lesions, there are no significant differences in rates of local residual recurrence between en bloc and piecemeal resections. The manner of recurrence and the biological characteristics of residual/recurrent tumors depend on whether the resected lesion is an adenoma, carcinoma in adenoma, de novo carcinoma, mucosal (m) or submucosal (sm) carcinoma. Therefore, it is essential to choose the appropriate method of follow‐up observation according to histopathologic findings of resected lesions. In local residual/recurrent lesions of intramucosal carcinomas, the treatment policy should be decided from an overall evaluation of histological findings on both recurrent and resected primary lesions. After EMR of sm carcinomas, attention should always be paid to both the loci of resection and possible metastasis during follow‐up observation; surgical treatment is inevitable in the case of recurrence.     

Factors influencing Helicobacter pylori eradication with 2 week combination therapy of lansoprazole and amoxycillin: Intragastric distribution of colonization and gastric mucosal atrophy

In Japan, gastric ulcers are often accompanied by marked gastric mucosal atrophy. We evaluated the dual therapy of double-dose lansoprazole and amoxycillin for Helicobacter pylori eradication in Japanese ulcer patients and investigated the effects of intragastric distribution of H. pylori colonization and gastric mucosal atrophy on eradication with this combination therapy. Seventy-six H. pylori-positive ulcer patients received lansoprazole (30 mg) plus amoxycillin (500 mg) twice daily for 2 weeks (LA-60 group), lansoprazole (30 mg once daily) plus amoxycillin (500 mg twice daily) for 2 weeks (LA-30 group) or lansoprazole (30 mg once daily) for 6 or 8 weeks (LPZ group). Infection was evaluated by light microscopy, culture and biopsy urease tests. Helicobacter pylori colonization was classified as localized to the corpus (localized type) or involving the antrum and corpus (whole type). Fundic mucosal atrophy was graded according to endoscopic and histological features. Eradication was achieved in 67.6% in the LA-60 group, 31.6% in the LA-30 group, and 0% in the LPZ group, and moderate or severe histological gastritis was improved in the LA-60 group. Eradication was better in localized-type colonization (92%) than whole-type (56%), and better with fundic mucosal atrophy (84%) than without, but poor in both whole-type colonization and scanty mucosal atrophy (47%). The LA-60 therapy achieves better eradication in Japanese ulcer patients with localized H. pylori colonization and/or gastric mucosal atrophy, which are likely to be important predictors for the successful eradication with dual therapy.     

Studies on the Prevalence of Complicated Atrial Arrhythmias, Flutter, and Fibrillation in Patients with Reciprocating Supraventricular Tachycardia Before and After Successful Catheter Ablation

Atrial flutter and AF are complications in approximately 30% of cases of paroxysmal supraventricular tachycardia (PSVT)-indicated catheter ablation, and it is of interest to determine if therapeutic modification for PSVT would eliminate combined atrial tachyarrhythmia like atrial flutter and AF. The aim of this study was to determine the incidence and the risk of atrial tachyarrhythmias after catheter ablation of PSVT. A total of 152 patients (age range 12-74, mean 41 +/- 17 years) with accessory pathway (n = 106) and/or dual atrioventricular nodal conduction (n = 46) were enrolled in a 2-year follow-up program after successful catheter ablation. Possible risks on clinical background (age, sex, PSVT duration, hemodynamic instability during attacks), premature atrial contraction (PACs) on Holter monitoring, echocardiographic left atrial size, and electrophysiological property (insertion site, conduction type, effective refractory period) were evaluated. Atrial flutter and AF were complications in 53 (35%) of the subjects, who were elderly and had a longer PSVT history with a larger left atrial dimension and frequent PACs; however, the electrophysiological properties were similar. After a 2-year follow-up period 36 (24%) of the patients still exhibited PAC runs, including 13 (9%) with atrial flutter and AF, each one of whom were complicated with nonlethal cerebral thromboembolism and congestive heart failure. Multiplelogistic-regression analysis revealed that advanced age (> or = 41 years, P = 0.0152) and frequent PACs (> or = 1% of total daily QRS counts, P = 0.0426) on Holter monitoring are the risk factors of PAC runs and/or atrial flutter and AF. In conclusion, successful ablation for PSVT is thought to be beneficial for preventing atrial flutter and AF. However, careful follow-up to monitor for the recurrence and atrial flutter and AF related complications, especially in patients of solitary atrial flutter and AF without reciprocating tachycardia and with frequent PAC.     

Optimal Programming of the Atrioventricular Delay Using the Phonocardiogram

Purpose: To predict the optimal atrioventricular (AV) delay using the phonocardiogram (PCG).
Methods: We studied 12 recipients of cardiac resynchronization therapy (CRT) system and eight recipients of dual-chamber pacemakers implanted for AV block with normal left ventricular (LV) function. The amplitude of the first heart sound (S1) was recorded by PCG and the LV outflow tract (OT) time-velocity integral (TVI) was measured by pulsed Doppler echocardiography. The AV delay was prolonged in 20-ms increments, from 60 ms to 240 ms. Ishikawa's method was used for the echocardiographic optimization of the AV delay. The relation between S1 amplitude and the AV delay was analyzed.
Results: The correlation between the amplitude of S1 and the length of AV delay showed an S-shaped curve. The AV delay at the inflection point of each patient's S-shaped curve (161.2 ± 19.5 ms) was positively correlated with the optimal AV delay determined by echocardiography (148.3 ± 16.9 ms, r = 0.83, P < 0.001). In addition, there was a positive correlation between the AV delay at the maximal TVI of LVOT (150.8 ± 22.7 ms) and the AV delay at the inflection point of the S-shaped curve (159.5 ± 24.9 ms, r = 0.87, P < 0.001). In two CRT system recipients, an optimal AV delay could not be found by echocardiography; however, an optimal AV delay could be determined by PCG.
Conclusions: A high correlation was observed between the optimal AV delay determined by phonocardiography versus echocardiography.