A nonparametric method for estimating interaction effect of age and period on mortality.

In this paper we introduce a new model and develop an estimation strategy to analyze mortality data. The model we dealt with has the specific structure E[log qij] = mu + alpha i + beta j + rho ij subject to the linear restrictions sigma i alpha i/sigma 2i = sigma j beta j = sigma i pij/sigma 2i = sigma j rho ij = 0 for any i and j; here, qij denotes the mortality for the jth period category and ith age category, mu denotes the overall mean, alpha i denotes the ith age effect in antichronological order, beta j the jth period effect, rho ij the general interaction effect; and sigma 2i is the common error variance of log qij for the ith age group. We propose a combined technique of ANOVA and nonparametric smoothing for estimating these parameters. The methods described are illustrated by mortality data on rectum cancer in Japanese males and females between 1950-1986.

Application of log-linear model in inference on karyotypic evolution in chronic myelocytic leukemia.

Relationships among additional chromosome abnormalities in chronic myelocytic leukemia (CML) with translocation 9;22 [Philadelphia chromosome (Ph1)-positive CML] were analyzed by log-linear models on 709 karyotypes reported in the literature. Additional abnormalities, such as the gain of chromosome 8 (+8), gain of Philadelphia chromosome (+Ph1), isochromosome of the long arm (q) of chromosome 17 [i(17q)], and the gain of chromosome 19 (+19), were frequently observed. A four-way 2 x 2 x 2 x 2 contingency table was considered with respect to the appearance of these four abnormalities, then the hierarchical log-linear models having at least four main effects were fitted to the observed contingency table. Akaike's information criteria of the models reflected the fitness of the model very well. Parameter estimates of the interaction terms indicated that the combinations of two abnormalities, '+8 and +19', '+Ph1 and +19', and '+8 and i(17q)' were positively associated, while '+Ph1 and i(17q)', and '+19 and i(17q)' were negatively associated. Based on the results of the data analysis, an inference was made on the route of karyotypic evolution in Ph1-positive CML; it statistically supports the hypothesis presented by Heim and Mitelman.

Estimation of chronic phase duration in Ph-positive chronic myelocytic leukemia treated with busulfan: statistical analysis on Japanese patients.

Chronic phase duration was analyzed in 148 Japanese patients with Ph-positive chronic myelocytic leukemia (CML) treated only with busulfan, and multivariate proportional hazard models were constructed to infer the prognosis of a given patient, and to evaluate the prognostic importance of the clinical findings. To make an accurate estimation of an individual patient's prognosis, we introduced a piecewise linear model for describing a hazard function in each prognostic variable. Of the 11 prognostic variables initially analyzed, the absolute count of peripheral basophils was revealed as the most important prognostic factor. A high basophil count was clearly a factor in cases with poor prognosis. The statistical model selection based on the criteria of model approximation finally suggested a model with three covariates; absolute count of peripheral basophils, platelet count, and presence or absence of additional chromosome abnormalities superimposed on the translocation of 9;22. By analyses based on the above model, we estimated that the median of the chronic phase duration for the patients with poor and good prognosis was 12 and 75 months, respectively. The piecewise linear model was well suited for an accurate estimation of an individual patient's prognosis. Thus, the model constructed here would become a reliable control to evaluate investigational approaches, such as hydroxyurea, interferons, and/or bone marrow transplantation.

Analysis and rearrangement of human karyotypes by computer.

A system useful for the collection and analysis of a large number of abnormal karyotypes and for studies on the relationship between cytogenetic abnormalities and clinical features of diseases is reported. The program is based on the disintegration and rearrangement of abnormal karyotypes recorded according to the 1978 International System for Human Cytogenetic Nomenclature (ISCN).

Study of stomach cancer in atomic bomb survivors. Report 1. Histological findings and prognosis.

For the purpose of studying the histological findings and prognosis of stomach cancer in atomic bomb survivors, a histological diagnosis of 600 cases of stomach cancer observed between 1964 and 1986 in three medical institutions in Hiroshima City was made by a single pathologist and, furthermore, analysis of 231 cases thereof was performed using the DS86 dose estimated by the Radiation Effects Research Foundation. 1) By histological type of stomach cancer, the frequency of poorly differentiated adenocarcinoma (poorly differentiated adenocarcinoma and signet ring cell carcinoma) was significantly higher in the 1 rad or more group (average stomach organ dose of 30.6 rad) than in the 0 rad group. 2) As for stromal type, the frequency of scirrhous type was significantly higher in the 1 rad or more group, but no difference in infiltrative behavior could be demonstrated. 3) Early cancer tended to be observed at a low rate in the 1 rad or more group. 4) As for average survival time, of the early cancers only well differentiated adenocarcinoma showed a significantly lower survival time in the 1 rad or more group when compared to the 0 rad group.

Acute and late effects of A-bomb radiation studied in a group of young girls with a defined condition at the time of bombing.

Ninety girl students have been identified, who were 14-15 years old when exposed to the atomic bomb while at the Central Telephone Office in Hiroshima located at a distance of 550 meters from the hypocenter. The mortality rate of the students exposed on the second floor of the building was estimated to be 50.9% and those exposed on the first floor (ground level) 33.3%. Doses to the students exposed on the second floor were estimated from cytogenetic evidence to be around 6 Gy in the T65 Dose system or appear to be 4 Gy in the DS86 system. These data indicate that LD50 is around 4 Gy in these young females. Among 28 students who were confirmed to be alive in 1965 and followed to the end of 1988, six students had breast cancer, mostly of invasive ductal type carcinoma. The incidence of breast cancer in the adolescent group was very high, the relative risk being 23.1 with 95% confidence limits of 12.9 to 42.2.

New mathematical modelling of blood lactate kinetics during ramp mode exercise in man.

The lactate (LA) kinetics of the whole body in exercise was described using the two-compartment model in consideration of the underlying physiological mechanism, and LA kinetics during the ramp mode exercise was analyzed. The estimated pattern of the glycolytic energy supply showed the progressive increase concurrently with the onset of ramp mode exercise and this pattern was just like a ramp phenomenon. Based on this result, it is proposed that blood LA kinetics during ramp exercise should be described mathematically as a continuous model, called "2nd-order model."

Comparison of objective methods for determining ventilatory threshold.

This study was undertaken to compare and re-examine the relation of lactate threshold (LT) and ventilatory threshold (VT), using six objective determination methods proposed previously. Twenty-one young male subjects performed a cycle exercise test in which the work rate was increased by 150 kg.m every 2 min up to his limit of volitional fatigue. Through each test, gas exchange parameter measurements were made every 1 min (every 30 s at nearly maximal level), and the venous blood samples were taken from a warmed ear lobe at each work rate for determining blood lactate concentration. LT and its variance were determined by the intersecting straight lines regression. LT ranged from 0.72 to 1.40 l/min in terms of VO2, and the mean value of S.D. for each LT was about 0.1 l/min. Each objective method for determining VT used in this study was based on the simple modelling of the criterion for visual detection of VT, that is the non-linear increase in VE or the systematic increase in VE/VO2. When the relationship between LT and VT was examined, VT by the objective methods based on determining minimum value of VE/VO2 showed relatively high consistency with LT. Of 16-20 individuals out of all 21 subjects, there were VT within LT +/- 0.2 in VO2. It is concluded that VE/VO2 is a more sensitive index for detecting VT than VE in the gas exchange parameters, and the objective VT determination method based on minimum value of VE/VO2 could facilitate estimation of LT within an error of +/- 0.2 l/min VO2 in most normal individuals.

Non-invasive automatic determination of anaerobic threshold using double gas exchange parameters.

A new technique for determining the anaerobic threshold (AT) in real-time during a progressive exercise test was proposed with special consideration to its safety. We applied the discriminant analysis based on the linear logistic regression model to two groups of gas exchange parameters at times just before and after the lactate (LA) threshold (determined by blood LA kinetics; the external criterion of AT) during the incremental exercise test in 21 young males. As a result, the selected variables for estimating AT accurately (the discriminant rate = 100%), were VE/VO2 and the relative change in VE. Our idea of the new technique for determining AT is based on the probability function (p(x)) derived from the discriminant analysis. At each time at which the gas exchange parameters are acquired during the exercise test, p(x) is calculated, and the decision whether the present exercise level is in the pre, just, or post-AT level is made by the p(x). The technique is able to stop the exercise test as quickly as possible after passing through the AT level. To evaluate the new technique, the data set of 66 females (aged 16-57) was applied as a form of simulation. It was shown that the exercise test could be stopped by the technique at a level of only 0.2-0.5 l/min in VO2 higher than AT. This advantage of the technique makes the exercise test safer for middle-aged or old men, and patients during cardiac rehabilitation.

Benchmark test of transport calculations of gold and nickel activation with implications for neutron kerma at Hiroshima.

A benchmark test of the Monte Carlo neutron and photon transport code system (MCNP) was performed using a 252Cf fission neutron source to validate the use of the code for the energy spectrum analyses of Hiroshima atomic bomb neutrons. Nuclear data libraries used in the Monte Carlo neutron and photon transport code calculation were ENDF/B-III, ENDF/B-IV, LASL-SUB, and ENDL-73. The neutron moderators used were granite (the main component of which is SiO2, with a small fraction of hydrogen), Newlight [polyethylene with 3.7% boron (natural)], ammonium chloride (NH4Cl), and water (H2O). Each moderator was 65 cm thick. The neutron detectors were gold and nickel foils, which were used to detect thermal and epithermal neutrons (4.9 eV) and fast neutrons (> 0.5 MeV), respectively. Measured activity data from neutron-irradiated gold and nickel foils in these moderators decreased to about 1/1,000th or 1/10,000th, which correspond to about 1,500 m ground distance from the hypocenter in Hiroshima. For both gold and nickel detectors, the measured activities and the calculated values agreed within 10%. The slopes of the depth-yield relations in each moderator, except granite, were similar for neutrons detected by the gold and nickel foils. From the results of these studies, the Monte Carlo neutron and photon transport code was verified to be accurate enough for use with the elements hydrogen, carbon, nitrogen, oxygen, silicon, chlorine, and cadmium, and for the incident 252Cf fission spectrum neutrons.

Hyperbaric oxygen therapy adjunctive to mild hypertensive hypervolemia for symptomatic vasospasm.

The efficacy of hyperbaric oxygen (HBO) therapy was evaluated retrospectively in 43 patients who developed symptomatic vasospasm following acute aneurysm surgery. HBO therapy was given as an adjunct to mild hypertensive hypervolemia in 24 patients. Before HBO therapy, 17 patients had no infarct (Group 1), and seven had infarcts (Group 2) caused by vasospasm. A further 19 patients received mild hypertensive hypervolemia alone (Group 3). Cerebral infarcts developed in four Group 1 and 12 Group 3 patients. A good outcome 1 month after surgery was achieved by 13 Group 1 (76%), one Group 2, and seven Group 3 patients (37%). Fifteen of the 24 patients who received HBO therapy responded to HBO exposure, and 12 responding patients (80%) had a good outcome. During HBO exposure, electroencephalographic improvements were all accompanied by neurological improvements. There were no complications related to HBO therapy. HBO therapy adjunctive to mild hypertensive hypervolemia is helpful in preventing cerebral infarction associated with symptomatic vasospasm.

[An international repatriation of a cervical cord injury patient who was under mechanical ventilation].

The patient was a 55-year old Japanese man, who had a traffic accident and suffered cervical cord injury in Thailand. Although he received an emergency operation and intensive care, he had respiratory paralysis and received a tracheostomy. One month after the accident, he still needed to receive mechanical ventilatory support. He and his wife hoped to return to Japan. We were asked to transport the patient from Bangkok to Tokyo. With some help from an assistance company, we could transport the patient safely from Bangkok to Tokyo on a commercial airline under mechanical ventilatory support. We experienced the several regulations and difficulties in performing medical treatment and transportation of a critical patient in a commercial airline.

[New approaches in neurosurgery and hyperbaric medicine--the importance of preventive and industrial medicine].

Neurosurgical patients have been mainly treated by surgical procedures over the past decades. In addition, hyperbaric oxygen (HBO) therapy in neurosurgery has been used in patients with ischemic cerebrovascular diseases, head trauma, spinal damage, postoperative brain edema and others. However, the main therapeutic methods for neurosurgical diseases have changed dramatically due to developments in radiological techniques, such as radiosurgery and intravascular surgery. With changes in therapeutic methods, HBO therapy may become a very important treatment option for neurosurgical patients. For example, HBO therapy combined with radiotherapy (UOEH regimen) and anticoagulant therapy appear to be very effective in the treatments of malignant brain tumors and ischemic cerebrovascular diseases, respectively. On the other hand, medical examinations under hyper- and hypobaric environments have not yet been fully studied in the central nervous system compared to those in the cardiopulmonary systems. Moreover, the mechanisms of cerebral lesions in decompression sickness and acute mountain sickness remain unclear. Clinical neurologic approaches are very important in these fields. Hence, clinicians and researchers skilled in both neurosurgery and hyperbaric medicine will be required for advanced treatment and preventive and industrial medicine.

Mortality statistics of major causes of death among atomic bomb survivors in Hiroshima Prefecture from 1968 to 1982.

A comparative study was made on mortality during a 15-year period from 1968 to 1982 between atomic bomb survivors resident in Hiroshima Prefecture and non-exposed controls. The mortality rate for all causes of death was lower in atomic bomb survivors than in the non-exposed, but the rate was higher among those directly exposed within about 1 km than in the non-exposed. The mortality rate for malignant neoplasms was higher in atomic bomb survivors than in the non-exposed, but that for cerebrovascular disease and heart disease was lower. In examining the rate for malignant neoplasms by site, the sites showing a high mortality rate among atomic bomb survivors were almost identical to the results of the Life Span Study. For these sites, the shorter the exposure distance the higher was the mortality rate. The rate for malignant neoplasms of the uterus and stomach, and leukemia was unnaturally high among early entrants whose period after issuance of atomic bomb survivor's health handbook was short. In observing the atomic bomb survivors by the level of family destruction due to the bombing as a socio-economic factor, a tendency was observed for the mortality rate for malignant neoplasms, diseases of blood and blood-forming organs, and peptic ulcer, to be higher among survivors with severe family destruction.

[Successful treatment of huge arteriovenous malformation in the basal ganglia].

This report describes successful therapeutic results of a huge and high flow arteriovenous malformation (AVM) in the left basal ganglionic region. A 39-year-old female was admitted to our hospital presenting recent progression of aphasia, hemianopsia, hemiparesis, hemisensory disturbance on the right side. Progression of disturbance in consciousness was rapid, and the patient became comatose shortly after admission. A CT scan revealed a densely enhanced lesion in the left basal ganglia which caused aqueductal obstruction and hydrocephalus. Angiography demonstrated a huge and high flow AVM that was supplied by the anterior and posterior choroidal arteries, the lateral striate arteries and the insular branches of the middle cerebral arteries. This AVM drained into the vein of Galen via the inferior ventricular and basal vein. The draining vein was markedly dilated at the level of midbrain by a prominent stenosis of the junction between the vein of Galen and straight sinus, and it severely compressed the midbrain. Superselective embolization of the feeding arteries was done in two sessions. This was followed by surgical intervention for the embolized AVM one month after the second session. Embolization and surgery were carried out under barbiturate protection to reduce the risk of normal perfusion pressure break-through. The patient recovered well from these interventions without any hemodynamic changes and showed dramatic improvement of all focal neurological abnormalities. Postoperative angiography showed only a small residue of AVM.

[Gliosarcoma associated with von Recklinghausen's disease: a case report].

A very rare case of gliosarcoma with von Recklinghausen's disease is presented. A 51-year-old man was admitted to our hospital in March 1990, because of a 2-month history of personality change and left hemiparesis. Multiple neurofibroma over his whole body with many café au lait spots had been present since early childhood. His mother, brothers and children also had café au lait spots. Neurological examination on admission revealed memory disturbance, left homonymous hemianopsia and left hemiparesis. CT scan showed a large lobular lesion in the right temporoparietal region. The medial hypodense part was sharply demarcated by a ring-like enhancement, while the lateral isodense part was homogeneously enhanced. MRI showed a sharply demarcated high intensity lesion with Gd-EDTA enhancement corresponding to the enhanced area on CT. Faint staining on angiography revealed that the blood supply to the tumor was predominantly dural. At surgery, the tumor was solid and highly vascular, and adhered tightly to the dura. The superficial part of the tumor was well demarcated from the brain tissue, but the demarcation was obscure in the deeper part. Histological findings showed two clearly defined neoplastic components: a gliomatous component that was stained for GFAP, and a sarcomatous component that had spindle-shaped nuclei and eosinophilic fibers. The patient underwent radiotherapy after surgery, but the tumor soon recurred. A second operation was performed, but the tumor had infiltrated into the scalp and he died 10 months after the first operation. This combination is very rare and has not been reported previously.

[Effect of smoking cessation on body mass index, blood pressure and serum lipids in middle-aged male workers].

The purpose of this study was to examine the effects of smoking cessation on body mass index (BMI), blood pressure and serum lipids in middle-aged male workers considering the effect of BMI which would increase by smoking cessation. The subjects were 1431 middle-aged men who worked in an enterprise in Hiroshima prefecture. Cross-sectional data measured in 1989 and longitudinal data measured from 1985 to 1989 were used in this analysis. The effect of smoking cessation on BMI, blood pressure and serum lipids were evaluated by two models of analysis of covariance (PC-SAS: GLM procedure) for the cross-sectional data and longitudinal data. In analysis of the cross-sectional data, model 1 was controlled for BMI and model 2 was not controlled for BMI. In analysis of the longitudinal data, model 3 was controlled for BMI change and model 4 was not controlled for BMI change. The main results are summarized as follows: 1. BMI was increased over the short period by smoking cessation, but over the long period BMI of ex-smokers remained at almost the same level as non-smokers'. 2. Blood pressure was increased over the short period by both the effect of smoking cessation and BMI increase from abstention from smoking. But over the long period blood pressure of ex-smokers remained at almost the same level as non-smokers. 3. Triglycerides (TG) and atherogenic index (AI) tended to decrease and HDL-cholesterol (HDLC) tended to increase over the short period by smoking cessation, but the concomitant BMI increase may have blunted any independent beneficial effect of smoking cessation on TG, AI and HDLC. But over the long period TG, AI and HDLC of ex-smokers recovered to almost the same level as non-smokers', and remained at that level. 4. These results suggest that smoking cessation have beneficial effects for health promotion in middle-aged men.

[Effect of habitual physical activity on physical fitness and serum cholesterol in middle-aged male workers].

The effects of habitual physical activity on physical fitness parameters and serum cholesterol profile were studied in middle-aged male workers. The subjects were 3376 middle-aged men (age: 30-59 yrs) who worked at two enterprises in HIROSHIMA Prefecture. As for physical fitness parameters, grip strength, vertical jump, side step, and step test scores were measured. Atherogenic index was calculated as (total Chol-HDL Chol)/(HDL Chol). Because daily physical activity mainly consists of physical activities during leisure time and working time, by using a questionnaire, physical activity during leisure time was assessed and categorized by frequency into three categories: 'frequently', 'sometimes', and 'seldom': and physical activity during work was categorized as 'high' or 'low' according to the average walking time per day during work. The effect of these physical activities on physical fitness parameters and serum cholesterol profile was evaluated by analysis of covariance (PC-SAS: GLM procedure) adjusting for several confounding factors such as age, body mass index, type of job, smoking and drinking habits. The main results are summarized as follows: 1) Physical activity during leisure time was positively related to vertical jump, side step, and step test score, independent of physical activity during working time, and 2) physical activity during leisure time was negatively associated to LDL-C and AI in the group with 'low' physical activity during work. These results show that in middle-aged male workers, even moderate or light physical activity during leisure time has some beneficial health promoting effects through changes in physical fitness and serum cholesterol profile.

[New quantification of regional cerebral blood flow measurements by 123I-IMP SPECT with the rotating gamma camera--theory and validation of the look-up table method].

A new method of quantifying regional cerebral blood flow (rCBF) measurements by N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT with a rotating gamma camera was designed. By assuming the 2 compartment model of the kinetic for 123I-IMP, two parameters of rCBF and distribution volume (Vd) of 123I-IMP from brom brain tissue to blood were obtained by the look-up table method and were derived from two simultaneous equations of the early and delayed images. The rCBF values of 3 cases (two normal adults and one brain infarct patient) were calculated by this method and were compared with the values of positron emission tomography (PET) measured at the same time. The average rCBF values in gray and white matter by this method were 40 ml/100 g/min, 27 ml/100 g/min, respectively and correlated significantly to rCBF values by PET (r = 0.598 (p less than 0.001)).

[Quantification of regional cerebral blood flow (rCBF) measurement with one point sampling by 123I-IMP SPECT].

A handy method of quantifying regional cerebral blood flow (rCBF) measurement by 123I-IMP SPECT was designed. A standard input function was made and the sampling time to calibrate this standard input function by one point sampling was optimized. An average standard input function was obtained from continuous arterial samplings of 12 healthy adults. The best sampling time was the minimum differential value between the integral calculus value of the standard input function calibrated by one point sampling and the input function by continuous arterial samplings. This time was 8 minutes after an intravenous injection of 123I-IMP and an error was estimated to be +/- 4.1%. The rCBF values by this method were evaluated by comparing them with the rCBF values of the input function with continuous arterial samplings in 2 healthy adults and a patient with cerebral infarction. A significant correlation (r = 0.764 (p less than 0.001)) was obtained between both.