Five handred sixty eight premature infants were admitted in the premature nursery of Kansai Medical University Hospital during 8 years from 1968 to 1975.102 infants of them developed IRDS, among whom 26 cases showed a course of Prolonged Respiratory Distress, suffering from tachypnea and cyanosis over four weeks duration. The author investigated clinically on these infants, especially on effects of oxygen administration for development of “Prolonged Respiratory Distress”, and the following results were obtained. (1) Out of twenty six Prolonged Respiratory Distress infants, eleven infants revealed characteristic signs of W-M Syndrome on chest x-ray finding. Two infants died of W-M Syndrome. All of twenty six Prolonged Respiratory Distress infants were born before 38 weeks of gestation and thein birthweights were under 2000g, several of them were small for dates babies. (2) Oxygen (FiO2,23-37%) were administered to prolonged respiratory distress infants untill central cyanosis was subsided. The durations were longer than 2 weeks, sometimes as long as 4 weeks.11 infants out of 26 prolonged respiratory distress revealed characteristic features of W-M Syndrome in chest x-ray. The W-M Syndrome Cases recieved oxygen therapy for 34 days in average, but O2 concentration administered was relatively low as 23-37%. (3) In this study series the author paid eff erts to shorten duration of O2 admimistration. Nevertheless, central cyanosis made it evitable to administer O2 longer than two weeks. Tachypnea had nothing to do with a reason of oxygen therapy. (4) Prolonged respiratory distress was diagnosed by long st anding respiratory distress with tachypnea and cyanosis longer than 4 weeks and characteristic finding of empyssma found in chest x-ray. (5) 45% of prolonged respiratory distress infants developed socalled lacey pattern (or bubbly pattern) in chest x-ray and became into W-M Syndrome. (6) Two out of eleven W-M Syndrome died of cor pulmo nale and their clinical coures were described in details, with histological findings. Prolonged Respiratory distres is a chinical course of recovery from IRDS, and an extrmely severe case is W-M Syndrome. Duration of O2 administration may have something to do with development of PRD from IRDS.
The medial thickness of the small pulmonary arteries was measured histometrically on sixty one autopsied cases, ranging from still born infants to five year old children. The studied cases were classified in to four groups. (1) Infants died of v arious diseases except of pulmonary disorders. (2) Wilson-Mikity Syndrome. (3) Massive aspiration syndrome of mature infants and hyaline menbrane disease of premature infants. (4) Congenital heart diseases. The results were summarized as follows. (1) Infants died of various disease s except of pulmonary disorders. a) The thickness of media at 100μ radius wide pulmo nary arteries were 1.47μ in embryos,9μ in neonates,7.8μ in six month infant,7it in one year old infant,6μ in two years old child,5.5p in three years old child, and 5μ in five years old child. The media of the small pulmonary arteries is relatively thick in embryonic period and becomes rapidly thinner after birth, especially remarkable by six months. After 6 months and up to 5 years decrease of the thickness is slow and it becomes the same as adult after 5 years. b) The media thickness of the small pulmonary arteries is rather thin in prem ature infants without. pulmonary disease. The thickness at 100μ radius wide arteries was ranging from 8.5μ to 3.5μ. ( 2 ) Wilson-Mikity S yndrome Thickness of the me dia at 10μ wide arteries showed the higest value,20μ in average. This thickest media may be caused by prolonged anoxia and resulted in pulmonary hypertension which is obviously effective to develop cor pulmonale in this syndrome. This observation is an important clue to study the causes of W-M Syndrome. (3) Massive aspiration syndrome of mature infants and h yaline menbrame disease of premature infants. In both mature and premature infants, thickness of the media at 100μ wide arteries were 11.7μ and 12.4μ in average, respectively. They were thicker than those of infants without pulmonary lesions. The thinning of the muscular media after birth would be insufficient in these pulmonary diseases. (4) Congenital Heart Diseases Thickness of the med ia at 10μ wide arteries was 13μ in average which is 2.4 times thicker than those of infants without pulmonary diseases. Though the variation was wide, it was likely that either anoxia or pulmonary hypertention causes a pulmonary vasoconstriction in some cases of congenital heart diseases then cases as in massive aspiration syndrome and hyaline menbrane disease.
Primary endocardial fibroelastosis is mainly the disease of infancy, but adult cases rarely have been reported. This disease is characterized by diffuse endocardial thickening due to the proliferation of elastic and collagenous tissue. The etiology and pathogenesis of this disease remains obscure. A boy reported here ha d been apparently in good health until the age of 11, since when palpitation, nausea, vomitting, facial edema and epigastric pain developed. On a chest x-ray examination the heart was found to be greatly enlarged (CTR: from 0.62 to 0.72)and an electrocardiographic study revealed QS-pattern and inverted T-wave. He received treatment with digitalization, and repeated hospitalization and discharge from hospital. At the age of 13, following a lapse of common cold, his congestive heart failure rapidly deteriorated and he died 16 months after the onset of congestive cardiac failure. At autopsy, the heart, weighed 370gm, was remarkably enlarged and hypertrophied, especially in the left ventricle. The endocardial surface of the left ventricle was smooth and yellow-white. Microscopic examination revealed diffuse proliferation of elastic and collagenous tissue in the endocardium, which had various thickness of about 500p to 3.0 mm. Multiple organizing thrombi were found in the mural endocardium of the left ventricle, some of which were covered by the thick layer of elastic and collagenous tissue. The myocardium of the left ventricle showed the mixture of atrophic and hypertrophic muscle fibers, furthermore fatty degeneration and diffuse interstitial fibrosis. Neither myocardial inflammation nor infarction was found. There were neither congenital cardiac anomalies such as Bland-White-Garland syndrome and aortic stenosis, nor the evidence of the congenital metabolic disorders such as glycogen storage disease. All the liver, spleen, lungs and other organs showed severe congestion, and especially the liver, weighed 870gm, did “nutmeg liver” -like appearance. On the basis of these clinical and pathological findings, it is supposed that slight endocardial fibroelastosis was present in the left ventricle of this boy from birth, and has been increased in thickness gradually over a very long period as the result of being affected by some factors such as an elevated intra-ventricular blood pressure and a long-standing mild ischemia of endocardium. For these reasons, he seems to have been able to maintain good health without cardiac symptoms or signs until the age of 11, despite the presence of the endocardial lesion. In conclusion, this autopsy case is regarded as a very rare and interesti ng one of primary endocardial fibroelastosis in point of having been able to survive until the age of 13.
Using dyes to observe the influence on capillary permeability produced by antibiotics (CBPC, SBPC, CET, and CEZ administered i. v. at 400 & 9mg/kg) in rats, the changes in dye concentrations in the blood vessels were examined at 5,15,30, and 60 minutes following antibiotic administration in comparison with i. v. NaC1 administration. The results were as follows 1) Using Ev a ns blue 25mg/kg: Evans blue was decreased after antibiotic (400mg/kg) i. v. administration at 5 to 30minutes, markedly so after 5 minutes. 2) Using Evans blue 5mg/kg or Rhodamine B 5mg/kg: These dye concentrations were decreased by antibiotics (400mg/kg)at 5 to 30 minutes, clearly so after 5 minutes, and by antibiotics (9mg/kg) at 5 to 15 minutes, the effects of the latter dosage being weaker than these of the former. 3) The Evans blue concentrations varied with the quantity of phys. NaC1 solution. 4) Using Histamine i. m. and i. v.: Evans blue concentrations were de creased by Histamine i. m. and i. v. at 30 to 60minutes, markedly so after 60 minutes. 5) Using Urokinase i. v.: Urokinase i. v. had no influ ence on dye concentration.
Using Evans blue to observe the influence on capillary permeability produced by antibiotics (CBPC, SBPC, CET, and CEZ administered i. v. at 400 & 9 mg/kg), the diameter changes in the bluing lesions induced on the dorsal skin of rats of histamine, bradykinin, and urokinase were measured at 5 and 30 minutes following antibiotic administration in comparison with i. v. NaC1 administration. The results were as follows: 1) Using Histamine: a) At 5 minutes, t h e diameter of the bluing lesion was increased by both administrations, the effects of the weaker administration being weaker. b) At 30 minutes, the diameter of the bluing lesion was increased by both administrations, their effects being the same. c) The effects of both admini s t rations were stronger at 5 minutes than they were at 30 minutes. 2 ) Using Bradykinin: a) At 5 minutes, th e diameter of the bluing lesion was increased by both administrations, the effects of the greater dosage being only slightly stronger than that of the lesser dosage. b) At 30 minutes, the diameter of the bluing lesion produced by the higher bradykinin concentrations were increased by both administrations. c) At 5 and 30 minutes, the effects o f the antibiotic administrations were about the same, but on lesions induced by low concentrations of bradykinin, the effects were slightly weaker at 5 minutes than they were at 30 minutes. 3) Using Urokinase: No effects of antibiotic administration could be observed. 4) The effects of CBPC, SBPC, CET, and CEZ were almost same.
The interactions between antibiotics, Evans blue, and serum protein were measured by the ultracentrifuge (300,000 X gravity) method. In addition, the effects of antibiotics on blood coagulation (prothrombin time, and partial thromboplastin time). platelet function (aggregation and adhesiveness), and electrolyte (Na, and K) were also observed. The results were as follows: 1) No interactions be tween antibiotics, Evans blue, and serum protein were seen. 2) No antibiotic influences on prothrombin time and partial thromboplastin t ime could be found. 3 ) No antibiotic influences on platelet aggregation and adhesiveness were present. 4) Electrolyte Na was slightly elevated by antibiotics (400mg/kg i. v. ), bu t electrolyte K was slightly lowered by the same ciosage. No antibiotic influence on electrolytes were shown by the lower dosage (9mg/kg). The results reported in P arts I, I I, and III suggest that antibiotics may increase capillary permeability, which may be the cause of their increasing concentration in the tissues and their changing rates of concentration (tissue/blood) following i. v. administration.
Pseudomonas aeruginosa is an ubiquitous organism in nature and has been thought to be low-virulent. The discovery and practical use of penicillin followed by exploitation of various antibiotics such as streptomycin and chloramphenicol, lead to the effective treatment of infectious diseases that were due to certain bacterial species. Gram-positive pyogenic cocci, representative of such organism, were successfully eradicated by therapeutic usage of these drugs whereas the cases of infection due to Gram-negative rods known as low-virulent or even non-pathogenic became increasingly important. This phenomenon is understood as “microbisme sèlectioné et substitute” or “opportunistic infection”. Although the discovery of gentamicin (GM) and penicillin delivatives such as carbenicillin and sulbenicillin resulted in fairly effective control of human P. aeruginosa infection, certain predisposed patients developed fatal infection due to this organism. In the present study, the author attempted to find an effective way to control human P. aeruginosa infection with a combined administration of GM, one of the most eff ective antibiotics for P. aeruginosa, and several samples of γ globulin (γ-G) in tests on experimental P. aeruginosa infection in mice. The bacterial strain used in this experiment was P. aeruginosa NC-5. Minimum inhibitory concentration (MIC) of GM against P. aeruginosa NC-5, estimated by broth dilution method, was 6.25 mcg/ml. ICR strain male mice,3 to 4 weeks old (about 15 grams), w ere infected with an intraperitoneal injection of 0.5 ml of bacterial suspension. GM combined with or without -G was intramuscularly injected shortly after the inoculation. The mice were o brserved for survival up to 3 days. The median lethal doses (LD50) of strain NC-5 to mice, estimated with and without mucin, were ca 10 3.2 cells/ml and ca 10 6.2 cells/ml, respectively. The results of therapeutic experiments obtained were as follows: 1. The median effective doses of GM for the mice challenged with 1,000 LD50 and 100LD50 of NC-5 were 312.5 mcg/0.1 ml and 70.7 mcg/0.1 ml, respectively. 2. Neither fractionated γ-G (150 mcg/0.1 ml) nor γ-G in. whole serum (500 mcg/0.1ml) of normal rabbits protected the mice against the challenge of 1,000 LD50 of the organism. But therapeutic effects were observed in the combined administration of 50mcg/0.1 ml (1/6 ED50) of GM and 250 mcg/O.1 ml of serum (or 150 mcg/0.1 ml of γ-G). 3. Anti-NC-5 rabbit serum was more effective than normal serum. That is, therapeutic effects were observed in the group treated with 200 mcg/0.1 ml of the antiserum or its γ-G. The combined usage of 25 mcg/0.1 ml (1/8 ED50) of antiserum γ-G and a 50 mcg/0.1 ml (1/6 ED50) of GM was markedly synergized. 4. The effect, of γ-G combined with GM was verified as the activity of a specific antibody by its absorption test with corresponding antigen. 5. IgG and IgM fractions from rabbit antiserum for NC-5 were compared with each other for their therapeutic effect. IgG, was more effective than IgM despite its lower agglutination titer. 6. In the group of mice treated with GM combined with γ-G (or IgG) the viable bacterial number in peritoneal exsudate was decreased and the animals survived. In the use of IgM instead of IgG, however, the decrease of viable bacterial number was less and the mice failed to survive. From the above described results, it was concluded that synergism between the antiserum or its γ-G and GM was observed in the treatment of experimental P. aeruginosa infection in mice. The mechanism of this synergism claimed that the bacteria were easily phagocytized by the opsonization with the antiserum or its γ-G, and GM exert bactericidal activity in cooperation with the host cells.
Statistical observations were made on the 102 leukemia cases observed during the past twenty-five years at the First Department of Internal Medicine of Kansai Medical University. The distribution of the cases as to age, sex, and disease type was similar to the statistical observations reported by other Japanese authors on the cases of the same era, except that the present cases showed a higher percentage of monocytic leukemia, and, during the final nine years of the era (1967-1975), a marked increase in myelogenous leukemia. A pronounced prolongation in survival time was observed among the recent cases. In concomitance with course prolongation, the main direct cause of death changed from bleeding to infection, but more recently, deaths from infection were seen tending to decrease. Hepatic function was checked by laboratory tests (GOT, GPT, alkaline phos phatase, total protein, and A/G ratio of sera) at each of the five clinical stages (KIMURA) of leukemia cases without any circulatory failure, severe infections, or drug intoxications: Abnormal data by these tests were more frequently encountered at the terminal stage as well as at the non-effective stage than at the remission of the disease; thus, the incidence of elevated alkaline phosphatase activity paralleled the severity of the clinical picture in myelogenous leukemia, while no significant abnormalities were found in lymphocytic leukemia. Comparing the results of these tests with the histological findings in the liver in eighteen autopsy cases without any severe circulatory disturbances, severe infections or drug intoxications, no significant correlations could be detected.
Experiment I: Both 18 70-day old and 15 29-day old male rats of the Sprague-Dawley JCL strain were administered TMBA 30mg/kg i. v. four times fortnightly. In 15 out of the 18 “effective” rats (i. e. those survived longer than four months after the first injection of TMBA),7 lymphatic,6 myelogenous, and 2 unclassified leukemia or subleukemic states were induced, while none of the 15 nontreated control rats yielded leukemia. Experiment II: Both 4 male and 5 female 63-day old rats and 6 fem ale and 5 male 28-day old rats of the Long-Evans strain were treated with DMBA 30mg/kg i. v. four times fortnightly. All four females out of the 7 effective rats yielded leukemic states of the erythroblast ic type. In addition, one case of lymphocytic leukemia was found among the 5 Sprague-Dawley males treated intragastrically with 0.72mg of DMBA 6 times a week in the age between 50-78 days and and another case of lymphocytic leukemia spontaneously occurred in an old male Wistar rat. In compariso n with 22 untreated controls and non-leukemically treated rats, the animals bearing chemically induced leukemia showed the following abnormalities: 1) anemia (RBC less than 2.5 million, hemoglobin content less than 30%) 2) thrombocytopenia (less than 100,000) 3) many atypical blood cells in the peripheral blood 4) loss of body weight and hepatosplenomegaly (average relative weight per body weight: liver 3.37%, spleen 0.38%)5) various degrees of leukemic cell colonization in the bone marrow, liver, spleen, lymph nodes, etc. In ord er to check the hepatic function of the hosts, the sera were examined for the enzymic activity of GOT, GPT, and alkaline phosphatase, total protein content, and the A/G ratio: Severe hypoproteinemia and a slight elevation of seral GPT were commonly observed in the leukemic animals. A fall in A/G and an elevation in alkaline phosphatase were also detected in the leukemic Sprague-Dawley rats, but not in the Long-Evans rats. This last finding did not seem to be strain-specific, but rather to be dependent on the leukemic states. It was of interest that high alkaline phosphatase activity was frequently observed among SD rats with diffuse leukemic cell infiltration of moderate grade into the hepatic lobules.
Over fist-sized Douglaus' tumor was found in a 27 year-old primipara complained of edema of the legs and abdominal pain at her 25 gestation weeks. At her 35 gestation weeks, she revealing general edema arid ascites entered into the Kouri Hospital of Kansai Medical University for the laparotomy. After the removal of 6,000m1 of hemorrhagic ascites, childhead-sized tumor without the peritoneal adhesion could be seen in the left ovary. In addition, many finger-sized nodular and hemorrhagic tumors were observed around the uterine cervical cannal, on the posterior wall of the uterus, and on the peritoneum of Douglaus pouch. No any tumors could be detected macroscopically on the right ovary, upper abdominal cavity, liver and digestive tracts. A female baby weighing 2,520g was delivered by cesarotomy, and she is growing up normally now. Bilateral tubo-ovariectomy, hysterectomy and extirpation of almost all tumors in the Douglaus pouch were performed. At the end of operation anti-cancer drugs were administered intraperitoneally. An oval, somewhat ragged ovarian tumor, sized 15 x 12 x 10cm and weighed ca 500g, had the uneven fibrous capsule, some parts of which were perforated by the hemorrhagic tumor tissues. On the cut surface,2/3 of the tumor was solid elements, in which bone, cartilage, brain, multivesicular tissue, and foci of hemorrhagic necrosis could be detected. and the other was multiple serous cysts. Macroscopic appearance of the metastatic tumors looked to be the solid primary tumor. Histologically, both abundancy of mature elements of 3 germ layers (Ectoderm; epidermis and its belongs, tooth and nervous tissue including chorioid plexus, Mesoderm; cartilage, bone, muscle and the other mesenchymal cells, Endoderm; bronchus, intestine and tubular epithels) and focally located few immature elements (nervous tissue including retinoblast and tubular structure including a glomeruloid body?)could be detected in 14 blocks of the primary tumor. On 15 blocks of the metastatic foci, the histologic appearances were mainly teratoma mixed with immature nervous elements. All metastatic foci were located in the peritoneal walls, and none of them infiltrated into the intraperitoneal organs. After the operation, her general condition was no good. She was suffered from severe anemia and died of respiratory insufficiency 8 months after the operation. In the postoperative course,5 times removals of abundunt, non-hemorrhagic ascites and a transitional elevation of α-fetoprotein in serum (3 days after the operation; 300ng/ml,2-3 months after the operation; 1060-2310ng/rnl, and thereafter; subnormal)were marked. Squamous epithelial cells could be detected in the ascites cytologically, and columnar epithels could be also found in the pleural fluids besides of the suspect for pulmonary metastasis on X-ray examination. Many points, e. g. histological classification of ovarian teratoma and her pathological diagnosis, ovarian immature teratoma and prognosis, metastasis of teratoma (ovarian teratoma with the elements of 3 germ layers in the metastatic foci), gliomatosis per itoni and tumor maturation, changes of serum 0a-fetoprotein in the neoplastic disease, and neoplasms in the pregnant women, were discussed, although her autopsy could not be done.