[in Japanese]

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Radionuclide ventriculography was made in 49 asymptomatic diabetic patients, aged 30-70 years, to investigate cardiac function. Comparisons were made with 33 age- and sex-matched non-diabetic controls.
Radionuclide ventriculography was performed at rest and during dynamic exercise by multigraded, supine bicycle ergometer. The resting left ventricular ejection fractions were similar between the diabetic patients and control subjects. No significant rise in the left ventricular ejection fractions during dynamic exercise was observed in the diabetic patients [58.4±9.8% (mean±SD) to 60.3±9.9] . In the control subjects, the left ventricular election fractions increased during dynamic exercise [59.3±8.4 to 63.0±11.4 (p<0.05) ]. Peak ejection rates were similar in both groups at rest [-2.62±0.64 (s^-1) vs-2.66±0.52] and during dynamic exercise [-3.25±0.74 vs-3.23±0.90] . Time to end-systole were similar in both groups at rest [315±42 (ms) vs 309±42] and during dynamic exercise [258±37 vs 262±37]. The resting peak filling rates were similar in both groups [2.27±0.62 (s^-1) vs 2.45±0.58], and the peak filling rates increased (p<0.001) during dynamic exercise in both groups [2.68±0.61 vs 3.28±0.74] . However, the percent changes of the peak filling rates were significantly lower in diabetic patients (p<0.001). In four of the diabetic patients, hypokinesis of the intraventricular septum was observed. No relation was indicated between the percent changes of the left ventricular ejection fraction and the value of HbA_1c in the diabetic patients. These results suggest that diabetic patients have less cardiac reserved performance.

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To evaluate the etiologic and pathophysiolagical characteristics of the aged cirrhotics, a total of 219 cirrhotic patients who admitted to our department between 1975 and 1989 was divided into the three age groups; ≤49 (Group A, n=70), 50-59 (Group B, n=77) and ≥60 (Group C, n=72) years and compared. The frequency of female patients was significantly higher in Group B and C than Group A, respectively. The age-related variation in etiologies of cirrhosis was analyzed among patients between 1975 and 1989, as well as those observed in 1990, when the assay for antibody to hepatitis C virus (anti-HCV) was available. Compared with Group A, patients with Group C had a lower incidence in HBsAg positive and alcoholic cases. The incidence in cases of unknown cause increased with age and in the elderly over 70 anti-HCV negative cases were found in approximately 45 per cent, the incidence being significantly higher than that of the 50-to-59 year age group. Of the Group C patients 10.6 Per cent had gastrointestinal bleeding, which was significantly lower in frequency as compared with 28.6 per cent of Group A. In contrast, the frequency of the other symptoms including jaundice, ascites and encephalopathy did not differ with age. Among various liver function indices the value of γ-GTP was significantly lower and that of cholesterol was significantly higher in Group C than in Group A, although albumin tended to decline with age. When the extent of endoscopic findings of esophageal varices were compared between the elderly over 60 and the under 60s, the former included the less advanced cases than the latter. The hemodynamic studies revealed that the portal pressure and hepatic blood flow did not differ among the three age groups, but the cardiac index reduced and total systemic vascular resistance increased with age. Regarding the cause of death, the frequency of gastrointestinal bleeding was lower in Group B and C than in Group A.
From these results it may be concluded that an approximately half of cirrhosis of the elderly occurs for no known cause other than HBV, HCV and alcohol, and that the frequency of gastrointestinal bleeding as well as the extent of esophageal varices appear to decline with age.

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In order to elucidate the nature of cardiovascular involvement in diabetes mellitus (DM), we analyzed a high-resolution time-activity curve obtained from a gated equilibrium radionuclide left ventriculography (RLVG) in 50 cases consisting of 3 groups; G-C: normal controls (n=17, male 10 and female 7, age 49.6±9.6 years old), G-DM: patients with DM without clinical signs of ischemic heart disease (n=17, male 13 and female 4, age 58.3±9.9 years old), and G-DM+MI: patients with DM complicated myocardial infarction (n=16, male 14 and female 2, age 59.5±10.0 years old). Indexes of cardiac performance during both systole and diastole obtained from RLVG were as follows: ejection fraction (EF), peak ejection rate (PER), peak filling rate (PFR), time from the start of systole to PER (T-PER₁), time from end-systole to PFR (T-PFR₂), diastolic relaxation rate (DRR) during the first third of diastole (DRRe) and during the whole diastole (DRRt).
There were no significant differences in EF and PER (systolic parameters) between G-C and G-DM. These parameters were significantly lower only in G-DM±MI. However, DRRe and DRRt (diastolic parameters) were significantly smaller, and T-PFR₁ and T-PFR₂ were longer in G-DM and G-DM+MI than in G-C. PFR was significantly lower in G-DM+MI than in the other two groups and there was no significant difference between G-DM and G-C. In addition, DRRe was significantly lower in patients with retinopathy than in patients without retinopathy in both G-DM and G-DM+MI.
It is concluded that DM can cause impairment of diastolic relaxation of the left ventricle before the appearance of distinct cardiac dysfunction during systole and that it might be probably due to microangiopathy. These results suggest a poor prognosis of MI in patients with DM.

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The pulmonary function and microscopic change of the lungs of diabetic patients were examined and compared with those of non-diabetic patients to assess the diabetic microangiopathy in lung.
For pulmonary function study, spirogram flow-volume curve, diffusing capacity and arterial blood gas analysis were performed in 52 diabetic patients and 48 age- and sex-matched control subjects. Diffusing capacity, % vital capacity, total lung capacity, residual volume and 25% maximal expiratory flow were significantly less in the diabetic group than in the control group. Pa0₂ was also decreased in the diabetic group. There were no significant differences between the two groups in the other parameters.
For histopathological study, the lungs of 35 autopsied cases of a diabetic group and 26 autopsied cases of a non-diabetic group. There were no significant differences in age and sex between the two groups. The two groups were compared and studied by measuring the thickness of alveolar capillary walls, pulmonary arteriolar walls and alveolar walls with a light microscope and an eye piece micrometer. The alveolar capillary walls, the pulmonary arteriolar walls and the alveolar walls had thickened significantly in the diabetic patients.
These studies suggested that histological changes (microangiopathy) in the lungs are a cause of pulmonary function abnormalities.

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Recombinant tumor necrosis factor α (TNF-α) significantiy enhanced epiderrnal growth factor receptor (EGF-R) expression in U373-MG glioma cell line as determined by binding of anti-EGF-R monoclonal antibody (MAb) 425. The optimal dose of TNF-α was 1000U/ml of media. When TNF-α was combined with recombinant interferon γ (IFN-γ), further upregulation of EGF-R was observed. However, IFN-γ itself did not show any EGF-R enhancement in this cell line. Scatchard analysis of receptor binding revealed that this enhancement of EGF-R expression was due to an increase in the EGF-R density. TNF-α did not affect expression of other brain tumor-associated antigens defined by MAb ASHE2, ASHG4 and ASAY1. Cultured fibroblasts showed no upregulation of EGF-R by TNF-α, suggesting a differential effect of TNF-α on EGF-R expression on glioma cells and normat cells.
We investigated whether TNF-α treatment of glioma cells increased the tumoricidal effects of radiolabeled MAb 425 which correlate with MAb density on tumor cell surfaces. Growth inhibition of glioma cells in culture by ¹²⁵I-labeled MAb 425 was significantly enhanced after treatment of the cells with TNF-α. In previous clinical trials, ¹²⁵I-labeled MAb 425 has shown immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with ¹²⁵I-labeled MAb 425 and cytokines.

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Of 242 patients who were given antiepileptic drugs (AEDs), 40 exhibited a high level of serum γ-glutamyl transpeptidase (γ-GPT). The significance of the high level was examined. “Antipyrine test” was also performed on 9 healthy controls and 39 patients with AEDs administration, and the antipyrine half-life (APt1/2), a reliable index for hepatic microsomal enzyme activity (MEA), was calculated for each subiect.
A high level of serum γ-GTP occurred more frequently in phenytoin (PHT) administered group than in PHT non-administered group. Furthermore, the maximam level was significantly higher in the former than in the latter. In 17 out of the 40 cases, the serum γ-GTP level was decreased to a normal level without reducing AED doses or stopping the AED administration, or changing to different AEDs. On the other hand, in almost all cases with AED administration, APt1/2 was shortened (i. e., induction of the microsomal enzyme). Furthermore, there was no correlation between serum γ-GTP level and APt1/2 in the cases with AED administration, indicating that the serum γ-GTP level was not a proper index for MEA. It was also shown that phenobarbital, PHT and carbamazepine, each being used alone within the therapeutic dose, could cause almost the maximal degree of hepatic micresomal enzyme induction.
Thus it is suggested that the elevation of serum γ-GTP level due to AED does not necessarily indicate hepatocellular damages. If this is accepted, it follows that even if patients with AED administration have a high level of serum γ-GTP, it is not necessary to reduce the AED doses, or discontinue them, or change to different AEDs.

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In 36 patients with acute myocardial infarction (AMI) ²⁰¹Tl single-photon emission computed tomography (SPECT) examinations were performed in a relatively early phase of AMI. The short and long axis views of the left ventricle (LV) were divided into 6 segments. Images of each segment were assigned scores (segmental scores) based on a visual evaluation of the extent of ²¹⁰Tl accumulations as follows: 1=normal; 2=relatively low; 3=low; 4=severely low; 5=cold. The sum total of the segmental scores constituted the SPECT score. SPECT scores were compared with maxGOT, maxLDH, maxCPK and maxCK-MB, Killip classification and Forrester hemodynamic subset on admission, and LV ejection fraction (LVEF). Segmental scores were compared with LV wall motion evaluated by left ventriculography.
The results are summarized as follows:
1) There were significant correlations between SPECT scores and maxGOT, maxLDH, maxCPK and maxCK-MB (r=0.62, r=0.60, r=0.51 and rn=0.39, respectively).
2) SPECT scores in patients with Killip group III were significantly higher than in patients with Killip group I+II (p<0.05). However, no significant differences in maxGOT, maxLDH, maxCPK and maxCK-MB were observed between patients with Killip group III and those with Killip group I+II.
3) SPECT scores were significantly higher in patients with Forrester group III+IV than in patients with Forrester group I+II (p<0.001).
4) Segmental scores in segments evaluated as akinesis, dyskinesis and aneurysm by left ventriculography were significantly higher than those evaluated as hypokinesis or normal (p<0.01, p<0.001). Segmental scores in segments evaluated as hypokinesis were significantly high in comparison with normal segments (p<0.001).
5) Significant correlations were observed between LVEF and SPECT scores (r=-0.74, p<0.001). However, LVEF correlated poorly with maxGOT, maxLDH and maxCPK (r=-0.45, r=-0.40, r=-0.47, p<0.05), and no significant correlation was observed between LVEF and maxCK-MB.
6) SPECT examinations were Performed in 11 patients in both the acute and chronic phase of AMI. SPECT scores in the chronic phase did not change in 4 patients, decreased in 5, increased in 2.
These results suggest that SPECT scores and segmental scores can be useful indices in the evaluation of AMI.

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Secondary vascularized flaps made from implanted vascular bundles in the subcutaneous tissues have dominant vascularities. Animal experiments were performed using white rabbits, two types of skin flaps were made on their backs. The first delay procedure was performed on the left side where the vascular bundle had been implanted with an elevation of distaiiy based flap (size 2cm×7cm). 28 out of 32, secondary vascularized skin island flaps survived either partially or completely in the first procedure. Moreover, the first delay method was observed to be efficacious in 15 out of 16 cases (p<0.01).
The viability of vascular bundles of secondary vascularized flap was thus proved. The first stage of the second delay procedure was performed in bilateral side using the same procedure as the first delay. Two weeks later, two types of delay method were carried out. On the left side, a proximally based flap (size 2cm×7 cm) was made at the distal area of the first delay flap. On the right side, a bipedicled flap was made (size 2cm × 14cm). These flaps were elevated as secondary vascularized skin island flaps two weeks later. In all cases, the latter procedure produced a longer survival rate compaired with the former (p<0.01).
It was concluded experimentally that the most effective second delay procedure was the bipedicled flap method.

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Effects of a 5-second external vibratory acoustic stimulation (VAS, 500Hz, 75db) were studied in 155 healthy pregnant women from 34 to 41 weeks' gestational age on the fetal heart rate and gross fetal body movement. Fetal behavioral states were also studied in 88 out of the 155 patients.
The following results and conclusions were obtained.
1) VAS induced significant increases in the fetal heart rate baseline, the mean amplitude, the mean duration, and the mean time spent % of fetal heart rate accelerations and gross fetal body movements.
2) VSA induced significant changes in fetal behavioral states at states 1F and 3F, but no changes in states 2F and 4F.
3) Reaction to VAS was recognized also in the low birth weight (<2, 500g) group, but the duration of the reaction was shorter than that in the normal (2, 500g) group.
4) By lowering the incidence of false non reactive NST with VAS test, it was possible to predict the fetal prognosis beter than NST alone.
5) Inasmuch as VAS changed the fetal behavioral state from resting phase to active phase, the use of VAS in addition to NST was very helpful in more accurate understanding of fetal heart rate monitoring.

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Macroscopical and histological studies were carried out to clarify nerve innervation of the sacroiliac joint which is believed to have a role in the development of low back pain. Eighteen Japanese adult cadavers were used for gross anatomical examination and six for histological examination of the nerve supply to the joint. The results were as follows:
1) It is suggested by the gross examination that the upper ventral portion of the joint is mainly innervated by the ventral ramus of the 5th lumber nerve.
2) The lower ventral portion of the joint was mainly supplied by the ramus of the 2nd sacral nerve or branches from the sacral plexus.
3) Lateral branches of the dorsal ramus of the 5th lumber nerve were considered to be the main nerves which innervated the upper dorsal portion of the joint.
4) The lower dorsal portion was innervated by nerves arising from a plexus composed of lateral branches of the dorsal rami of the sacral nerves.
5) The nerves which innervate the joint range in diameter from 0.292mm to 0.997mm, and no difference was found among those in the four subdivisions of the joint.
6) Histological examination revealed that nerve fibers and the terminals were present in the joint eapsule and adjoining ligaments. The nerve fibers varied from 0.2μm to 2.5μm in diameter and ended with five morphologically different terminals.

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[in Japanese]

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[in Japanese]

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