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.     

Solid-phase synthesis of human osteocalcin by using a γ-carboxyglutamic acid derivative

Human osteocalcin, also called bone Gla protein (BGP), consisting of 49 amino acids with two to three γ-carboxyglutamate residues, was chemically synthesized for the first time by a novel solid-phase peptide synthesis. An l -enantiomer of N-tert-butyloxycarbonyl-γ,γ′-dicyclohexyl-γ-carboxyglutaniic acid was designed, prepared and utilized as a monomeric compound and proven to be useful for the solid-phase peptide synthesis of human osteocalcin. The synthesis and optical resolution of the γ-carboxyglutamic acid (Gla) derivative are first described, followed by the synthesis and characterization of Gla¹⁷-human osteocalcin.     

Loss of heterozygosity and analysis of mutation of p53 in hepatocellular carcinoma

Abstract Thirty-six hepatocellular carcinoma (HCC) tissues obtained from 34 patients were classified according to histological diagnosis into six well-differentiated HCC, 20 moderately differentiated HCC and 10 poorly differentiated HCC. High molecular weight DNA was prepared from each tumour and the corresponding non-tumour tissue. Loss of heterozygosity (LOH) on chromosomes 4q, 5q, 10q, 11p, 16q, 17p, mutation of the p53 gene and polymorphism of intron 25 of the retinoblastoma (RB) gene were simultaneously analysed. The patients were composed of three cases of small HCC (the diameter of which was < 3 cm) and 31 cases of advanced HCC. Twenty-nine of 34 (85.3%) patients analysed had been exposed to hepatitis B virus and/or hepatitis C virus. The frequencies of LOH on seven chromosomes were 57.9% in 17p13.3, 45.1% in 17p, 45.1% in 11p, 41.9% in 5q, 41.9% in 16q24, 29.0% in 4q, 25.8% in 10q in advanced HCC (four of well differentiated, 18 of moderately differentiated and nine of poorly differentiated carcinoma). In contrast, LOH was observed on 4q, 5q, 16q and 17p in 33% (1/3) of the small HCC (two of well differentiated and one of moderately differentiated carcinoma). The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC. LOH on every chromosome and the p53 mutation were observed more frequently in more advanced tumours, and the genetic changes accumulated with the increase of the histopathological grade. These findings suggest that the accumulation of genetic changes in multiple tumour suppressor genes is involved in the progression of HCC.     

Effects of oral nizatidine on preoperative gastric fluid pH and volume in children

We have studied the effect of oral nizatidine 6 mg kg^–1in total on preoperative gastric fluid pH and volume in children.One hundred and four healthy children, aged 4–11 yr, wereallocated randomly to four groups (n=26): placebo administeredat 21:00 and 06:30 the night before and on the day of surgery,respectively (placebo-placebo: control); nizatidine 6 mg kg^–1at 21:00 and placebo at 06:30 (nizatidine-placebo); placeboat 21:00 and nizatidine 6 mg kg^–1 at 06:30 (placebo-nizatidine);and nizatidine 3 mg kg^–1 at 21:00 and 06:30 (nizatidine-nizatidine).Each child ingested a large volume of apple juice 3 h beforeestimated induction of anaesthesia. After induction of anaesthesia,pH and volume of gastric fluid obtained via an orogastric tubewere measured. Mean pH in the placebo-nizatidine and nizatidine-nizatidinegroups was significantly higher than that in the placebo-placebogroup (5.7 (sem 0.3), 6.0 (0.3) vs 1.8 (0.2), respectively)(P<0.05). Mean pH in the nizatidine-placebo group was similarto that in the control group (2.3 (0.3) vs 1.8 (0.2)). The numberof children with pH < 2.5 and volume > 0.4 ml kg^–1in the nizatidine-nizatidine (0%) and placebo-nizatidine (4%)groups was reduced compared with the control (46%) or nizatidine-placebo(38%) group. These data suggest that oral nizatidine 6 mg kg^–1in total, if given at one dose on the morning of the day ofsurgery or in two equal doses at bedtime before surgery andon the morning of surgery, may have a role in the prophylaxisof acid aspiration syndrome. Further studies are needed to determinethe optimal dose and safety of the drug in children.     

Analysis of Early Gastric Cancer Cases Collected from Major Hospitals and Intitutes in Japan

An analysis of 17,212 lesions from 15,933 patients with earlygastric cancer collected from 110 major hospitals and institutesin Japan is presented. The percentage of patients with early gastric cancer was highamong persons in their 60s and 50s. The sex ratio (F/M) was0.5 but it was higher for younger people than for old people.Regarding distribution of the types of early gastric cancer,the depressed group (Types IIe, III) accounted for 73.9% andthe elevated group (Types I, IIa) accounted for 15.3%. The elevated group was more frequent in the older age group.In regard to the type and invasion, slight invasion was prominentin types lIb and IIa, while deep invasion was prominent in IIa+ IIc. The metastatic rate was 18.4% for IIa + IIc, 11.8% forI and 11% for IIe. The frequency of lymph node metastasis was+4% in intramucosal cancer, 18.9% in submucosal cancer and 11.4%in total. The type in which multiple cancers were most frequentwas lIb, followed by IIa. The percentage of differentiated adenocarcinoma was 91.9% inthe elevated group and was found more often among the aged. Undifferentiated adenocarcinoma occurred more often among theyoung. The relationship between site and histology, locationand invasion, location and lymph node metastasis etc. were alsoinvestigated. We believe that these results should be very usefulfor detection and treatment of early gastric cancer. The rate of detection of small cancer is increasing year byyear. This increase can be explained by the progress and widespreadapplication of endo-scopy, which will continue to play a largerole in diagnosis and treatment of gastric cancer.     

CONCURRENT GASTRIC AND COLONIC LOW‐GRADE MUCOSA‐ASSOCIATED LYMPHOID TISSUE LYMPHOMATA IN A PATIENT WITHOUT HELICOBACTER PYLORI INFECTION

Mucosa‐associated lymphoid tissue (MALT) lymphomata observed simultaneously in the stomach and colon are rare. We report concurrent gastric and colonic low‐grade MALT lymphomata that originated from the same clone in a 58‐year‐old Japanese man without Helicobacter pylori infection. Endoscopy showed multiple erosive lesions in the gastric body and antrum, and a single flat elevation with an irregular margin in the sigmoid colon. Histopathological findings of both lesions suggested low‐grade MALT lymphoma. Lymphoepithelial lesions were evident in the gastric lesions, but not in the colonic lesion. Southern blot analysis of lymphoma cells revealed the same immunoglobulin heavy‐chain rearrangement pattern. The chromosomal translocation t(11;18)(q21;q21) was also observed. After six courses of cyclophosphamide, doxorubicin, vincristine and predonisolone, the gastric lesions disappeared endoscopically, while the colonic lesion persisted. A sigmoidectomy was consequently performed. The chromosomal translocation may be related to the pathogenesis of the present MALT lymphoma case without H. pylori infection. It is interesting that the gastric and colonic lesions differed in response to treatment and in their endoscopic and histologic features, despite having the same origin.     

Partial attenuation of the cardiovascular responses to tracheal intubation with oral manidipine

We conducted a placebo–controlled, randomized, and double–blinded study to evaluate the efficacy of manidipine given orally in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation. Thirty normotensive patients (ASA physical status 1) undergoing elective surgery were allocated to one of three groups (n= 10 for each); placebo, 5 mg manidipine, and 10 mg manidipine groups. These tablets were orally administered 3 h before induction of anaesthesia. Anaesthesia was induced with thiopentone 5 mg kg^-1 iv , and tracheal intubation was facilitated with vecuronium 0.2 mg–kg^-1. Laryngoscopy lasting 30 sec was attempted 2 min after induction of anaesthesia. Patients receiving placebo showed a significant increase in systolic and diastolic blood pressure associated with tracheal intubation. These increases following tracheal intubation were significantly reduced in patients receiving manidipine 10 mg compared with patients receiving placebo or manidipine 5 mg ( P < 0.05). Oral administration of manidipine 10 mg before induction of anaesthesia is a simple and effective method for attenuating pressor response to laryngoscopy and tracheal intubation. We stressed that the potential beneficial effect of a reduced haemodynamic reaction to intubation might be obtained at the expense of hypotension later on.     

Early Cancer of the Stomach Treated Successfully with an Endoscopic Neodymium-YAG Laser

A 61-year old man with poor pulmonary function was seen with two early cancers of the stomach. Neodymium-YAG laser treatment was applied to these lesions since surgery was contraindicated. The lesions were treated four times. Both tumors completely disappeared and the patient was left with ulcer scars that formed three to seven months after the treatment. Our results suggest that endoscopic Nd-YAG laser therapy is applicable in the treatment of early gastric cancer when a surgical operation is contraindicated.