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Biomedical subjects

N Hamajima

Publications and source records attributed to N Hamajima.

At least 91 records · Page 5Linked to original sources

Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan.

OBJECTIVES: The purpose of this study was to examine the hypothesis that tea and coffee consumption have a protective effect against development of digestive tract cancers. METHODS: A comparative case-referent study was conducted using Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) data from 1990 to 1995 in Nagoya, Japan. This study comprised 1,706 histologically diagnosed cases of digestive tract cancers (185 esophagus, 893 stomach, 362 colon, 266 rectum) and a total of 21,128 non-cancer outpatients aged 40 years and over. Logistic regression was used to analyze the data, adjusting for gender; age; year and season at hospital-visit; habitual smoking and alcohol drinking; regular physical exercise; fruit, rice, and beef intake; and beverage intake. RESULTS: The odds ratio (OR) of stomach cancer decreased to 0.69 (95 percent confidence interval [CI] = 0.48-1.00) with high intake of green tea (seven cups or more per day). A decreased risk was also observed for rectal cancer with three cups or more daily intake of coffee (OR = 0.46, CI = 0.26-0.81). CONCLUSIONS: The results suggest the potential for protective effect against site-specific digestive tract cancer by consumption of green tea and coffee, although most associations are limited only to the upper category of intake and have no clear explanation for site-specificity.

Adult↗

Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene.

Dihydropyrimidinase (DHP) deficiency (MIM 222748) is characterized by dihydropyrimidinuria and is associated with a variable clinical phenotype. This disease might be associated with a risk of 5-fluorouracil toxicity, although no cases have been reported. We present here both the molecular characterization of the human DHP gene and, for the first time, the mutations causing DHP deficiency. The human DHP gene spans >80 kb and consists of 10 exons. It has been assigned to 8q22, by FISH. We performed mutation analysis of genomic DNA in one symptomatic and five asymptomatic individuals presenting with dihydropyrimidinuria. We identified one frameshift mutation and five missense mutations. Two related Japanese adult subjects were homozygous for the Q334R substitution, whereas two other, unrelated Japanese infant subjects were heterozygous for the same mutation, but this mutation is not common in the Japanese population. A Caucasian pediatric patient exhibiting epileptic attacks, dysmorphic features, and severe developmental delay was homozygous for W360R. Using a eukaryotic expression system, we showed that all mutations reduced enzyme activity significantly, indicating that these are crucial DHP deficiency-causing mutations. There was no significant difference, in residual activity, between mutations observed in the symptomatic and those observed in the asymptomatic individuals.

Adult↗

Nested consent design for clinical trials.

BACKGROUND: Since random treatment allocation is hardly understood by the majority of patients, a new 'nested consent design' for clinical trials is proposed. PROPOSED DESIGN: The design consists of a two-step enrollment of study subjects. The first step is the enrollment of participants into a follow-up study, where consent to be subjects involved in the follow-up is obtained. The second step is the enrollment of randomly sampled eligible participants into a new treatment group. After the explanation of (1) treatment mode, (2) additional burdens associated with the proposed treatment and (3) expected effects and possible adverse events, written informed consent is obtained. Those who reject participation and those who are not allocated into the new treatment are treated by standard care. Endpoints are set to be the same for all follow-up study participants whether allocated into the new treatment or not, and follow-up is carried out in the same manner. Analyses are performed between those allocated to the new treatment and those non-allocated on an intent-to-treat basis. EXAMPLE: Although not a clinical trial, this design was applied in a smoking cessation program at Aichi Cancer Center Hospital for first-visit patients who answered in a questionnaire survey that they were smokers. Out of 1330 necessary participants, 324 were enrolled in the follow-up study during the first three months of enrollment. CONCLUSIONS: The design was found to be feasible for prevention trials, and possibly for clinical trials to compare a new treatment with a standard treatment. There seems to be no ethical difference between this design and the one-arm study design.

Clinical Trials as Topic↗

Patients' views on residual blood use for research purposes.

In order to document patients' views on residual blood use for research purposes, a questionnaire survey was conducted at Aichi Cancer Center Hospital in October 1997. Subjects were patients who had undergone blood tests at a central blood sampling room in the morning during the week of the study enrollment. The questionnaire was handed out and collected at a waiting area in front of the blood sampling room. Of the 583 patients to whom we tried to hand out the questionnaire, 558 participated (258 males, 294 females, and 6 of sex unknown) and 25 refused. Those who regarded research to improve health care as important were 76.7% of those sampled. Only 28 patients (5.0%) answered that they would not permit the use of their residual blood for research purposes. Although logistic analysis did not detect significant factors influencing the giving of permission, the percentage who would not permit the use of their residual blood for research purposes was significantly higher in cancer outpatients (6.7%) than in inpatients (1.0%). It seems desirable for hospitals to establish an open policy concerning residual blood use for research purposes.

Blood↗

Smoking and dietary risk factors for cervical cancer at different age group in Japan.

The importance of the major risk and protective factors for cervical cancer in women by age group was evaluated with the use of data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. This study included 416 cervical cancer cases and 20,985 referents confirmed as free of cancer. Cases and referents were divided into three age groups: the younger, middle and older age groups (30-44, 45-54 and 55-69 years old, respectively). Logistic model was applied separately to the three groups to estimate odds ratios (ORs) of smoking, beverage and dietary habits with adjustment for marital and reproductive factors. The elevated OR of current smokers was observed consistently in all age groups, while alcohol intake did not show any increased ORs. Dietary control for health lowered ORs for all three age groups, and the effect appeared to be more pronounced among the older age group (OR = 0.49, 95% confidence interval: 0.30-0.80). Higher frequency intake of green-yellow vegetables consistently afforded lower ORs among all three age groups. This risk increment of smoking and risk reduction by dietary control were consistent in all age groups. These findings suggested practicable prevention strategy for the cervical cancer by modifying general life style.

Acculturation↗

Agreement of endoscopic findings and serum pepsinogen levels as an indicator of atrophic gastritis.

Serum pepsinogen I and II levels have recently become popular as indicators of atrophic gastritis in epidemiological studies. Previous studies show a significant association between serum pepsinogen levels and endoscopically diagnosed atrophic gastritis. This study assesses the level of agreement between the degree of atrophic gastritis as assessed by endoscopic examination and by serum pepsinogen assays. Study subjects were 200 outpatients at Aichi Cancer Center Hospital, Nagoya, Japan, who were endoscoped between February and August 1995. Agreement of the degree of atrophic gastritis was assessed by endoscopic examination and by serum pepsinogen levels. Agreement in assessing the extent of atrophic gastritis between the two methods was 57%, and the presence of atrophic gastritis was 79%. Serum pepsinogen assays identify the majority of patients with atrophic gastritis, although they are less useful in assessing the degree of atrophy in detail.

Adult↗

[A randomized controlled trial with methotrexate (MTX), 5-fluorouracil (5-FU) and pirarubicin (THP) vs 5-FU alone in advanced or recurrent gastric carcinoma. Tokai Hokuriku THP Study Group].

A randomized controlled trial was designed to investigate the therapeutic benefit of a combination chemotherapy consisting of MTX, 5-FU and THP in patients with advanced or recurrent gastric carcinoma. The patients were randomized into two groups; Group A patients (n = 37) underwent our combined chemotherapy, whereas Group B (n = 34) underwent chemotherapy with 5-FU alone as a control. There were no significant differences in various background factors between the groups. The median survival time was roughly 170 days after the randomization for the patients with advanced cancer (n = 26 for Group A and n = 25 for Group B), with no significant difference between the groups. Two long survivors, however, belonged to Group A. The median survival time of 161 days for Group A (n = 11) was longer than that of Group B (84 days, n = 9), but the difference was not statistically significant. The incidence of toxicities (leukopenia in particular) exceeding JCOG grade 3 was significantly higher for Group A, but no morbidity was observed. These results imply that patients with advanced or recurrent gastric carcinoma may benefit from a regimen of MTX, 5-FU and THP.

Aged↗

Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity.

5-Fluorouracil (5-FU) is used widely in the treatment of several common neoplasms. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. Several recent studies have described a pharmacogenetic disorder in which cancer patients with decreased DPD activity develop life-threatening toxicity following exposure to 5-FU. We reported recently the first Japanese case of decreased DPD activity accompanied by severe 5-FU toxicity. The present study describes the results of molecular analysis of this patient and her family, in which three novel mutations (Arg21Gln, Val335Leu, and Glu386Ter) of the gene coding for DPD were identified. We also revealed that Arg21Gln and Glu386Ter are on the same allele and that Val335Leu is on the other allele, on the basis of analysis of the family genome. Expression analysis in Escherichia coli showed that Val335Leu and Glu386Ter led to mutant DPD protein with significant loss of enzymatic activity and no activity, respectively. The Arg21Gln mutation, however, resulted in no decrease in enzymatic activity compared with the wild type. The present data represent the first molecular genetic analysis of DPD deficiency accompanied by severe 5-FU toxicity in a Japanese patient.

Antimetabolites, Antineoplastic↗

Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia.

The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) developed MDS/AML; 8 of these were within 36 months of the diagnosis of AA, much earlier than previous reports. Six of the 11 children received rhG-CSF exceeding 10 microg/kg/d, and 9 received rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no development of MDS/AML among 41 children treated with either CSA or rhG-CSF or among 48 children who underwent bone marrow transplantation. A well-controlled clinical trial is warranted to determine whether therapeutic modalities affect the development of MDS/AML in children with severe acquired AA.

Acute Disease↗

Epidemiological features of first-visit outpatients in Japan: comparison with general population and variation by sex, age, and season.

To evaluate the methodological issues in using first-visit outpatients as controls in epidemiological studies, the features of general lifestyles of non-cancer outpatients at Aichi Cancer Center Hospital (ACCH) were compared with those of the general population, and their variation by sex, age, and season was determined by using a self-administered questionnaire. The study included 1231 subjects randomly selected from the Nagoya electoral roll (CRG), and three groups of non-cancer ACCH outpatients living in Nagoya; 800 from the period September to December 1992 (OPG1), 2326 from January to December 1992 (OPG2), and 12,243 from January 1991 to December 1992 (OPG3). In the younger age group, the proportion of current smokers was higher in the CRG than in the OPGs. In the older age groups, the proportion of those who consumed fresh vegetables and fruit everyday was higher in the OPGs than in the CRG. For other items, the features of the OPGs were not significantly different from those of the CRG. Among the OPG3, there were differences in the features of general lifestyles between sexes and consumption of several food items varied with age. Seasonal variation, however, was only observed in the specific food items where supply varied seasonally. It was concluded that, with due consideration of age, sex, and season in the analysis, it is feasible to use non-cancer outpatients as controls in epidemiological studies.

Adult↗

Case-control study of leukemia and diagnostic radiation exposure.

A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.

Adolescent↗

Estimation of adult T-cell leukemia incidence in Kyushu District from vital statistics Japan between 1983 and 1982: comparison with a nationwide survey.

To investigate the change in adult T-cell leukemia incidence between 1983 and 1992 and to evaluate the sensitivity of the nationwide adult T-cell leukemia survey, we estimated adult T-cell leukemia incidence in the Kyushu district, southern Japan, where adult T-cell leukemia is endemic. The incidence of adult T-cell leukemia was calculated from the difference between Kyushu and the rest of Japan in mortality from malignant lymphoid neoplasms, i.e., Kyushu's excess rate was assumed to be due to adult T-cell leukemia. In Kyushu, average annual adult T-cell leukemia cases aged > or = 20 years were estimated for men as 252 during the period 1983-87 and 341 during 1988-92, and for women as 201 and 246 respectively. The age-adjusted mortality rate tended to be higher in the latter period [6.29 per 100000 (95% confidence interval 5.59-7.00) vs. 5.25 (4.60-5.90) in men, and 3.33 (2.85-3.80) vs. 3.18 (2.71-3.66) in women]. By contrast, the registered number of adult T-cell leukemia cases nationwide during 1988-93 was only 35% (203/587) of the estimated number, and the number of registered versus estimated cases decreased with age, especially when cases were > 60 years old. In conclusion, the estimated adult T-cell leukemia incidence for 1983-92 increased in the latter half of the period. The estimation suggests that 65% of adult T-cell leukemia cases might be missed by a nationwide survey, and older cases were more likely than younger ones to be missed.

Adult↗

A new macroscopic classification predicts prognosis for patient with liver metastases from colorectal cancer.

OBJECTIVE: The authors defined a new macroscopic classification of liver metastases from colorectal cancer. SUMMARY BACKGROUND DATA: There were different prognostic results after the same operative procedure for liver metastases with similar background factors. METHODS: Eighty-one resected liver metastases were classified into simple nodular (SN) or confluent nodular (CN) types according to the characteristics of the cut surface of the tumor. RESULTS: The 5-year survival rates after hepatectomy were 41.7% for the SN lesions (n = 39) and 23.1% for the CN lesions (n = 42). The difference between the survival curves was statistically significant (p = 0.0307). Multivariate analysis using Cox's proportional hazards model revealed that the macroscopic type (p = 0.023), the tumor diameter (p = 0.0001), and the presence of lymph node metastases (p = 0.0016) were statistically significant independent prognostic factors. CONCLUSION: The new macroscopic classification may be valuable as a prognostic factor reflecting the biologic behavior of liver metastases.

Colorectal Neoplasms↗

Lifestyle and anti-Helicobacter pylori immunoglobulin G antibody among outpatients.

Since eradication of Helicobacter pylori (H. pylori) is thought to be a preventive measure against stomach cancer, several studies have examined factors associated with the infection. This paper reports the association of the infection with lifestyle factors observed in a hospital-based case-control study. Cases were 140 anti-H. pylori IgG antibody-positive outpatients (75 males and 65 females). Controls were 52 antibody-negative outpatients (22 males and 30 females). Both groups had undergone gastroscopy at Aichi Cancer Center Hospital between February 1995 and February 1997, and lifestyle data collected on the first visit were linked to calculate odds ratios. A strong association was observed with smoking among males; age-adjusted odds ratio (OR) = 7.85, 95% confidence interval (CI), 2.03-30.4. Rice breakfast (OR = 3.74; 95% CI, 1.30-10.8) and soybean paste soup (every day vs. occasionally, OR = 5.24; 95% CI, 1.80-15.2) were also associated with antibody positivity in males, but not in females. In females, pickled Chinese cabbage (> or = 1/week vs. < or = 3/month, OR = 2.82; 95% CI, 1.06-7.48) and lettuce (> or = 1/week vs. < or = 3/month, OR = 2.90; 95% CI, 1.09-7.76) were significantly associated with positivity. Multivariate analysis gave similar estimates for the above factors. Although the association between smoking and H. pylori infection has not been detected in past studies of a general population, except one recent one, this study on outpatients suggested a possible association. Smoking may work as a cofactor disturbing incidental eradication of H. pylori by antibacterial agents administered for other reasons.

Adult↗

Impact of family history on the risk of breast cancer among the Japanese.

To assess the impact of family history on the risk of developing breast cancer, a case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. In total, 1,551 breast cancer cases were included and 28,450 women, confirmed as free of cancer, were recruited as the reference group. The odds ratios (ORs) and their 95% confidence intervals (95% CIs) were estimated by using an unconditional logistic regression model. Stratification by age at diagnosis was done to evaluate the impact of family history on early (< 40 years of age) vs. later (> or = 40 years of age) onset. New findings obtained from the present study were as follows. 1) For women having a family member with ovarian cancer, the OR for breast center diagnosed under age 40 was 5.04 (95% CI: 1.48-17.1). 2) The effect of family history on the risk of breast cancer was greater when a sister(s) was (were) positive (OR = 3.51) than when the mother was positive (OR = 1.47). 3) The estimated proportional ratio (PR) for breast cancer was 2.63 (95% CI: 2.05-3.38) among sisters excluding probands, while PR for cancers other than breast cancer was 1.09 (95% CI: 0.94-1.27). This result suggested that a family history of breast cancer, especially among sisters, elevated the risk of developing breast cancer. Furthermore, when women had a sister(s) with breast cancer diagnosed prior to 40 years of age, their family history of breast cancer affected their risk of cancer of the breast and other organs.

Adult↗

Patients' views on reference to clinical data.

In order to survey patients' views on reference to clinical data for research purposes, an anonymous self-administered questionnaire was distributed to Aichi Cancer Center Hospital patients in 1995. All eligible first-visit outpatients (97 persons), randomly selected revisit outpatients (99 persons), and all eligible inpatients in a good condition at discharge except six cases (97 persons), responded to the questionnaire. Out of 293 patients (115 males, 174 females and 4 unspecified), 85.3% (standard error 2.1%) considered that hospitals should make active efforts to improve their health care and treatment skills. And 88.1% (standard error 1.9%) answered that reference to their own clinical data to improve health care and treatment skills was "preferable" or "don't mind".

Adult↗