Various surgery techniques performed on 26 advanced cancer patients using forehead, deltopectoral(D-P) and musculocutaneous(M-C) flaps were reviwed. The D-P flap presents few cosmetic problems in the head and neck region and can be used in elder patients because of little operative invasion. The M-C flap allows for reconstruction of defects in a one-stage operation which may shorten hospitalization and permit an ealier return to social life. The forehead flap is the most durable and reliable flap among them for reconstructive surgery, though it offers some cosmetic problems. In reconstruction of the esophagus after a pharyngolaryngoesophagectomy for cancer of the hypopharynx and the cervical esophagus, it seems more advantageous to use a hige flap in reconstruction than Bakamjian's original method since early detection of a local recurrence of the tumor is rendered easier with the former. There were no fatal postoperative complication, though minor necrosis, fistula, suture insufficiency and esophageal stenosis were observed, but improved with conservative treatment. Conseqently, the reliability and versatility of pedicle and muculocutaneous flaps were confirmed.
As to the prognosis, the 2-year survival rate was 42.2%. The cause of death was local recurrence in 4 patients, who all died within two years, and distant metastasis in 4 patients, who all died within one year of the operation. Local recurrence and distant metastasis were also seen in 4 patients who survived.

View full abstract

An electrode was implanted to stimulate unilaterally the mesencephalic ventromedial tegmentum (VMT) in 27 adult cats. Abnormal involuntary movements (AIM) such as contraversive head turning, bucco-lingual movements and choreoathetoid movements of the contralateral forelimb were elicited by high frequency electrical stimulation (20-100 Hz); the cats were unrestrained. Such AIM were abolished by damaging the thalamic ventrolateral nucleus ipsilateral to the stimulated side.
In order to investigate the neural pathway related to AIM, kainic acid (2μg) was injected stereotaxically into either the caudate nucleus or the globus pallidus in cats which had AIM during electrical stimulation of the VMT. These experimentally produced AIM did not changed with injection of kainic acid into the ipsilateral anteroventral part of the caudate uncleus, but were abolished by injection either into the ipsilateral rostromedial part of the caudate nucleus or into the globus pallidus. It was confirmed histologically that the intracerebral microinjection of kainic acid produced degeneration of nerve cell bodies and dendrites near the injection site while not affecting axons terminating in or passing through it.
These results suggest that the neural pathway arising from the substantia nigra and leading to the ventrolateral thalamus via the rostromedial part of the caudate nucleus and the globus pallidus are essential in producing AIM by electrical stimulation of VMT, and that this neural pathway contains at least one synapse each within the caudate nucleus and the globus pallidus.

View full abstract

The effects of histamine and its analogues on the cyclic AMP levels in the submandibular glands of guinea pigs and the characteristics of the receptors which mediate such effects were investigated.
Histamine and 4-methylhistamine dose-dependently increased the cyclic AMP levels in chopped submandibular glands. The ED₅₀ values for histamine and 4-methylhistamine were approximately 1.3×10^-5 M and 2.2×10^-5 M, respectively. 4-Methylhistamine had a higher efficacy than histamine. 2-(2-Pyridyl)ethylamine was far less effective than either histamine or 4-methylhistamine.
Although metiamide markedly inhibited the cyclic AMP-increasing effects of histamine and 4-methylhistamine, mepyramine was completely ineffective. A combination of aminoguanidine and quinacrine had no influence on the effect of histamine on the cyclic AMP levels.
From these results it was concluded that histamine H₂-receptors which mediate the cyclic AMP increase are present in the guinea-pig submandibular gland.

View full abstract

The in vivo antitumor activity of NCS-immune IgG (NCS conjugated with rabbit IgG antibody against the human leukemia cell line NALL-1) was evaluated in immunosuppressed newborn Syrian hamsters implanted with a transplantable human leukemia cell line (BALL-1). After i.p. injection of the conjugate, hamsters preinoculated i.p. with BALL-1 cells survived longer than hamsters treated with control solutions (p<0.01). The control solutions included NCS, immune IgG, a mixture of NCS and immune IgG, NCS-normal IgG conjugate and physiological saline. Growth retardation was not observed in NCS-immune IgG treated hamsters. The growth of s.c. implanted BALL-1 tumors was inhibited by i.p. administrations of NCS-immune IgG, however, the degree of inhibition was not significantly different from that obtained by NCS alone, a mixture of NCS and immune IgG or NCS-normal IgG conjugate. These results indicate that NCS-immune IgG was effective against i.p. implanted BALL-1 tumors, but was no so effective against s.c. implanted tumors.

View full abstract

Substrate-permeable cells were prepared by treatment of Rous Sarcoma virus-induced mouse ascites sarcoma cells (SR-C3H/He) with a low concentration of digitonin. Using relatively small amounts of the digitonin-treated permeable cells, mitochondrial functions such as a respiratory rate, respiratory control ratio(RCR), and ADP/O ratio of oxidative phosphorylation were easily measured by the oxygen electrode method. The permeable ascites sarcoma cell mitochondria had a slightly lower RCR and ADP/O ratio than mitochondria isolated from mouse liver and ascites sarcoma cells. This result was found to be mainly due to higher extramitochondrial Mg²⁺-ATPase activity in the permeable ascites sarcoma cells. The effects of hexokinase and pyruvate kinase on the RCR and the ADP/O ratio were investigated by the additions of glucose and phosphoenolpyruvate as substrates, but these enzymes can not be the main factors in decreasing the RCR and the ADP/O ratio in the permeable ascites sarcoma cells since the glycolytic pathway was not continuous in these cells. The digitonin-treated permeable cell system is an extremely useful system for studying mitochondrial functions and their relations to other organelae and metabolic pathways under near in vivo conditions.

View full abstract

This study was undertaken to clarify the characteristics of pneumatization with aging by measuring the area of temporal pneumatizations of malformed ears as shown in roentgenograms. Roentgenograms of 23 patients afflicted unilaterally and 8 bilaterally with congenital atresia auris with microtia were examined. These patients, aged 3 to 27 years, were admitted to the Department of Otolaryngology, Okayama University Medical School Hospital for surgical treatment from January 1953 to Novembar 1978. A considerable number of X-ray photographs of normal ears of outpatients of the same hospital were used for statistical comparison during the same period.
It was revealed that the area of pneumatization was statistically smaller in the malformed ear, and that the correlation between the area of pneumatization and age was high in the nomal ear. There was some difference between the bitateral and unilateral cases as to the mode of the development. In bilateral cases, it was thought that the development of pneumatization might have occurred during the embryonal stage and be attributable to congenital causes. Pneumatization in unilateral cases might have been influenced strongly by postnatal suppression.

View full abstract

⁴⁵Ca uptake by rat peritoneal mast cells was observed, and the inhibitory effect of nifedipine, a Ca²⁺ antagonist, on ⁴⁵Ca uptake by mast cells, stimulated by an antigen, comp. 48/80, concanavalin A and Ca ionophore A 23187, was examined. The increase in ⁴⁵Ca uptake by mast cells induced by the antigen paralleled the increase in mast cell number. A significant increase in the uptake of ⁴⁵Ca by mast cells was observed with the stimulation by the antigen, comp. 48/80, concanavalin A and Ca ionophore A 23187. The increased uptake of ⁴⁵Ca induced by antigen was inhibited by nifedipine, and this dose-dependent inhibitory effect of nifedipine on ⁴⁵Ca uptake was also observed in the mast cells stimulated by comp. 48/80, concanavalin A and Ca ionophore A 23187.

View full abstract

A pancreatic function test (PFT) by peroral intake of a synthetic peptide (N-benzoyl-L-tyrosyl-P-aminobenzoic acid) was performed on 29 healthy controls and 131 patients with various pancreatic diseases in order to evaluate its validity and limitations. PFT was found to be a simple and useful exocrine pancreatic function test with good reproducibility. PFT values were significantly lower in patients with noncalcified chronic pancreatitis, pancreatolithiasis, pancreatic cancer, pancreatectomy or acute pancreatitis than in healthy controls. Furthermore PFT values were abnormal in 13.6 percent of 22 patients with suspected chronic pancreatitis, 78.1 percent of 32 patients with noncalcified chronic pancreatitis, 81.5 percent of 27 patients with pancreatolithiasis and 88 percent of patients with pancreatic cancer. Mild damage of the pancreas could not be detected by PFT, though moderate to severe damage could be in most cases. As for pancreatic cancer, the PFT values were not abnormal unless the main pancreatic duct was obstructed within 6 cm of the Vaterian papilla, and as for chronic pancreatitis, values were abnormal only when dilatation of the pancreatic duct was accompanied by stenosis, irregular margin, rigidity and/or obstruction. Evaluation of patients who had undergone a pancreatectomy indicated that PFT values were abnormal when more than the proximal half or the distal three-fourths of the pancreas was resected. PFT was useful in following up recovery from acute pancreatitis. PFT is slightly less sensitive than the pancreozymin secretin test in detecting exocrine pancreatic dysfunction, and a normal PFT value does not necessarily rule out pancreatic disease.

View full abstract

A comparative study of a pancreatic function test utilizing a synthetic peptide(PFT) and the pancreozymin secretin test (PS test) was performed to evaluate the validity and limitations of PFT. PFT was found to be less sensitive than the PS test in detecting exocrine pancreatic dysfunction. PFT values were always abnormal when the exocrine pancreatic dysfunction was moderate to severe; i.e., the amylase output 40, 000 units, maximal bicarbonate concentration 70 mEg/l and secretory volume 55 ml. When the pancreatic dysfunction was of a milder degree, PFT values were abnormal only half of the time. Consequently, a normal PFT value does not necessarily rule out pancreatic disease. PFT can give a false positive result in cases of cirrhosis of the liver, irritable bowel syndrome and renal insufficiency. When renal insufficiency is ruled out, a PFT value of less than 65 percent is diagnostic of pancreatic dysfunction. A PFT value of 65-70 percent can be obtained in diseases of other organs such as cirrhosis of the liver and irritable bowel syndrome. PFT is not as sensitive as the PS test, but it is a simple and useful exocrine pancreatic function test. It is an especially good screening test for pancreatic diseases.

View full abstract

A comparison of blood flow and myocardial oxygen consumption (MVO₂) in the right and left ventricles was made in 24 open-chest dogs. Simultaneous measurements were made of the left anterior descending (LAD) and right coronary arterial (RC) blood flow, and of O₂ saturation in the coronary sinus and in from one to four anterior cardiac veins. Blood flow was greater in the LAD than in the RC, 87.4±36.0 and 46±22.0 ml/min/100g, respectively. The O₂ extraction was 51.3±11.0 in the anterior cardiac veins and 60.0±6.3% in the coronary sinus. The mean MVO₂ was greater for the left than for the right ventricles, 8.6±3.3 vs. 4.0±2.1 ml/min/100g. An increase in LAD flow without an increase in O₂ extraction accounted for the enhancement of MVO₂ of the left ventricle induced by pacing, isoproterenol or methoxamine. In contrast, pacing, isoproterenol or constriction of the pulmonary artery increased MVO₂ of the right ventricle with an increase in both O₂ extraction and right coronary blood flow. These results indicate that the right coronary arterial blood flow is lower per unit weight of tissue and is less dependent on MVO₂ than is LAD blood flow.

View full abstract

A cardiovascular epidemiologic survey was performed in three areas (Sakuto-cho, Sanyo-cho and Osafune-cho) of Okayama prefecture in 1981 to determine age and sex differences in serum HDL-and total-cholesterol. A total of 1077 subjects, 389 male and 688 female, with 412 under 60 years of age (younger group) and 655 over 60 years of age (elder group) were studied, and the following results were obtained. The ratio of HDL-cholesterol to total-cholesterol in subjects from the mountain town of Sakuto-cho was higher than in those from urban areas (Sanyo-cho and Osafune-cho). In the female group, HDL-and total-cholesterol values were higher and the HDL- total-cholesterol ratio lower than in the male group. Among healthy individuals, the value of HDL-cholesterol was higher in the younger and female groups. However, in the female group, the total-cholesterol value was also high, so there was no significant difference between sex concerning the HDL-cholesterol to total-cholesterol ratio. In those with hypertension, ECG abnormalities and obesity, we found a higher total cholesterol level and lower HDL-cholesterol to total-cholesterol ratio than in the healthy subjects. This tendency was especially remarkable in the elder group. We found no differences in the HDL-cholesterol values according to sex and age. However there was lower HDL-cholesterol to total-cholesterol ratio in the female group than in the male group resulting from a higher total-cholesterol value in the former.

View full abstract

A total of 55 patients were treated with ifosfamide on two different treatment schedules. Twenty-four patients (22 with bronchogenic carcinomas and two with metastatic lung tumors) received 50 mg/kg of ifosfamide each day for three consective days, every three weeks (Regimen I), and the remaining 31 patients (24 with bronchogenic carcinomas and seven with metastatic lung tumors) received 40 mg/kg each day for five consective days, every three weeks (Regimen II). All patients had disseminated cancer, and 20 had had prior chemotherapy. Of the 20 evaluable patients with bronchogenic carcinoma who underwent Regimen I, five patients with small cell carcinoma had positive responses (one complete and four partial), whereas seven patients with other histologic cell types did not respond to the treatment. Of two metastatic lung tumor patients under Regimen I, one with cervical carcinoma had a partial response. The overall response rate for Regimen I was 6/22 (27%). With Regimen II, of 22 evaluable patients with bronchogenic carcinoma, nine (seven with small cell carcinoma, one with adeno carcinoma and one with squamous cell carcinoma) had partial responses. Of seven evaluable patients with metastatic lung tumor, two patients with cervical carcinoma had positive responses (one complete and one partial). The overall response rate for Regimen II was 11/29 (38%). Myelosupressive toxicity was mild: leukopenia (less than 2, 000/cmm) occurred in 12% of the patients under Regimen I and 6% under Regimen II, and thrombocytopenia (less than 100, 000/cmm) in 12% under Regimen I and 3% under Regimen II. Bladder toxicity occurred in 50% of the patients under Regimen I and 52% under Regimen II. Upper gastrointestinal symptoms, such as nausea and vomiting occurred in one half of the patients under either Regimen. In conclusion, there were no significant differences in response rate and toxicity between the two treatment schedules. Ifosfamide appears effective in the management of disseminated cervical carcinoma, as well as small cell lung carcinoma. The agent should be considered in combination with other active agents in the treatment of bronchogenic carcinoma.

View full abstract

A new method for quantitative analysis of ifosfamide and its active metabolite, 4-hydroxy-ifosfamide, was applied to determine the optimal mode of administration of ifosfamide. Three each of six patients with extensive bronchogenic carcinoma were given a single 40mg/kg dose of ifosfamide by either a five-minute or 60-minute intravenous infusion, with a second course of treatment 7-21 days later. Using the NaOH method, the pharmacokinetics was investigated to determine which administration schedule, the five-minute or 60-minute infusion, was preferable for the treatment of clinical malignancies. Ifosfamide was quite stable, but 4-hydroxy-ifosfamide was labile in blood samples, though immediate extraction with dichlorethane minimized the lability of 4-hydroxy-ifosfamide. The distribution volume and the transfer constant into 4-hydroxy-ifosfamide of ifosfamide were rather large, while the transfer constant for urinary excretion was rather small after the 60-minute infusion. The amount of unchanged ifosfamide excreted into urine was larger and its excretion more rapid after the five-minute infusion. As for 4-hydroxy-ifosfamide, the elimination constants and the maximum concentration in the blood were similar for both schedules, but the distribution volume was larger after the 60-minute infusion. The urinary excretion of 4-hydroxy-ifosfamide was delayed and the ratio of 4-hydroxy-ifosfamide to unchanged ifosfamide was larger after the 60-minute infusion. These results suggest that the 60-minute intravenous infusion is preferable to the five-minute intravenous infusion.

View full abstract

Using the Raji cell radioimmunoassay (RCRIA) reported by Theofilopoulos et al., 26 serum samples from systemic lupus erythematosus (SLE) patients were evaluated. All of those patients had definite granular immune deposits in renal biopsy specimens, and the presence of circulating immune complex in these patients was also suspected. RCRIA values of these patients were generally higher than those of normal human sera.
RCRIA values were compared with other serological parameters of SLE including serum complement (CH₅₀), serum gammaglobulin, anti-double stranded DNA antibody, anti-nuclear ribonucleoprotein (RNP) and anti-lymphocyte antibody. There was no correlation between the RCRIA values and anti-lymhocyte antibody. The correlation with CH₅₀ was also rather negative. There was positive correlations between the RCRIA values and serum gammaglobulin and anti-ds DNA antibody. However there were four serum samples which were negative to anti-ds DNA antibody but high RCRIA values. Three samples had high anti-RNP antibody titiers. The data suggest that not only the ds-DNA antigen-antibody system, but also other kinds of antigen-antibody systems may compose the circulating immune complex. The RCRIA values of sera from SLE patients using Raji cells killed by 100% acetone instead of living cells were generally higher. The increases in the RCRIA values were regarded as being due to the participation of antinuclear antibodies present in the patients' sera. Thus, in evaluating SLE sera, there is the possibility that the RCRIA may give false positive results due to the presence of antibodies, including anti-nuclear antibodies, which react with Raji cells. As long as this possibility is kept in mind, the RCRIA value may become a valuable serological index of SLE.

View full abstract

Using the Raji cell radioimmunoassay of Theofilopoulos et al, soluble immune complex (IC) in sera from 26 patients with systemic lupus erythematosus was measured. The distribution and amount of renal immune deposits were examined.
According to the distribution of glomerular immune deposits, patients were divided into four groups. There were 3 patients with the focal segmental mesangial pattern, 8 with the diffuse global mesangial pattern, 11 with the granular pattern and 4 with the membranous pattern. In 2 of the 3 patients with the focal segmental mesangial pattern, serum IC levels were only slightly elevated and mesangial immune deposits were very light. In 7 of the 8 patients with the diffuse global mesangial pattern, serum IC levels were markedly elevated with large amount of mesangial glomerular immune deposits in spite of minimal urinary finding. In patients with this pattern, wide deviation of serum IC levels was observed. In 7 of the 11 patients with the granular pattern, marked elevation of serum IC levels was observed. Three patients with sclerotic glomerurlar changes had relatively low serum IC levels. In 3 of the 4 patients with the membranous pattern, serum IC levels were low. Of the 26 patients of this study, 12 having renal interstitial deposits had higher serum IC levels than 14 patients without renal interstitial immune deposition. This difference was statistically significant. There were no relationships between the serum IC levels and the grade of hematuria or proteinuria.
The data suggests that the serum IC levels measured by the Raji cell radioimmunoassay may give us some information about the degree of renal immune deposition and become a useful index of lupus nephritis.

View full abstract

There are two major surgical procedures for pure or predominant mitral stenosis, open mitral commissurotomy (OMC) and mitral valve replacement (MVR). The purpose of this study was to assess the left ventricular (LV) function and exercise tolerance after mitral surgery by these procedures.
Forty-eight patients underwent mitral valve surgery, and were divided into 3 groups, namely, Sellors type I+II (OMC, 18 patients), Sellors type III (OMC, 13 patients) and Sellors type III (MVR, 17 patients). Björk-Shiley disc prosthetic valves were used in most of the MVR cases.
Although the incidences of the NYHA Class (III+IV) in the Sellors type I+II, Sellors type III and MVR groups were 44.4%, 76.9% and 64.7%, respectively, before surgery, they improved to 0%, 15.4% and 5.9% postoperatively. No remarkable changes in the CI of the Sellors type I+II and Sellors type III groups were recognized through the entire postoperative period, but in the MVR group, both the CI and SVI increased significantly 6 months after the operation compared to preoperative values. The postoperative LV function at rest was best in the Sellors type I+II group (OMC), moderate in the MVR group and worst in the OMC patients of the Sellors type III group. The same results were recognized when scored using the NYHA functional classification. Six months after the operation, both the CI and SVI during exercise markedly decreased in the Sellors type III and MVR groups, and no improvement in the exercise tolerance of either group was recognized. Also, the Heather index increased significantly in comparison with preoperative values. Therefore, improvement in LV contractility and exercise tolerance hoped for in valvular reconstructive surgery was not realized. On the contrary, there was a tendency to become worse at the 6th postoperative month.
It is difficult to decide whether to reconstruct or to replace a severely distored mitral valve. Considering the above results, we conclude that OMC of a remarkably distored valve was not necessarily indicated since the possibility of postoperative restenosis and regurgitation is rather high. In light of postoperative LV function and exercise tolerance, MVR seems preferable to OMC.

View full abstract

This paper describes a new type of penicillin action on the cytoplasmic membrane of Escherichia coli. The ability of filamentous cells to uptake amino acids induced by low concentrations of penicillin increased with cell elongation. This defect in amino acid transport was mostly observed on the substrate of the osmotic shock resistant transport system. Penicillin treatment, however, did not disturb the other membrane functions such as the uptake of α-D-methyl glucopyranoside and triphenylmethylphosphonium ion.

View full abstract