MORPHOLOGICAL DIFFERENCES IN HEARTS OF RATS WELL ADAPTED AND POORLY ADAPTED TO CHRONIC HYPOXIA

We carried out an experiment to analyze morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia. Male and female Wistar rats, 1 week, 4 weeks and 9 weeks old, were employed on the assumption that adaptive ability was dependent on age and sex. These rats were raised at an altitude of 2,400 m and were kept for 7 to 9 weeks. Control groups were maintained at an altitude of 600 m during the same period of time. Each group consisted of 4 to 6 rats. At the end of the experiment, body weight, heart weight, ratio of heart weight to body weight and hematocrit were measured, and ventricular wall thickness, myocardial fiber diameter, capillary supply and mitochondria were morphometrically studied. Of the 6 experimental groups, the 4-week-old male rats (M2) had the highest body weight, as compared with the other experimental groups. In addition, relative to these other experimental groups, the following features were found for M2. Heart weight was intermediate, heart weight/body weight ratio was low and hematocrit was also low. Ventricular wall thickness was intermediate in the right ventricle (RV) and interventricular septum (IVS) but was thin in the left ventricle (LV). Myocardial fiber diameter was intermediate in the RV, large in the IVS and small in the LV. Capillary supply was intermediate in the RV and dense in the IVS and LV. Mitochondria were small but cristal density and percentage area, estimated from electron micrographs, were found to be high. These data showed that in well developed rats under chronic hypoxia, there is good development of capillary supply with corresponding restriction of cardiac hypertrophy, while hematocrit count and mitochondria are also affected.     

ALPHA FETOPROTEIN and GARGINOEMBRYONIC ANTIGEN PRODUCING HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) showing marked elevation of serum alpha fetoprotein (AFP) (maximum; 70942.0 ng/ml at the end stage) and serum carcinoembryonic antigen (CEA)(maximum; 7368.4 ng/ml at the end stage) was surgically resected. In the resected liver, there were two different tumor nodules which were adjacent to each other but clearly separated by a thin connective tissue. One of the nodules was a well differentiated and the other was poorly differentiated HCC. Immunoperoxidase study revealed that both CEA and AFP were localized in the tumor cells of the poorly differentiated HCC. This is the first report which clearly proved CEA synthesis in the cells of HCC. Serial staining showed that there was simultaneous synthesis of CEA and AFP in some of the tumor cells. ACTA PATHOL. JPN. 35: 969–974, 1985.     

Effect of dobutamine on the arterial ketone body ratio and portal blood flow velocity in cirrhosis

ABSTRACT— We studied the relationship between the portal blood flow velocity and the arterial ketone body ratio in patients with chronic liver disease receiving a dobutamine infusion. We used an ultrasonic Doppler duplex system to evaluate the portal blood flow velocity. Dobutamine was given intravenously at 5 μg/kg/min for 20 min. Dobutamine infusion induced smaller changes in the portal blood flow velocity and ketone body ratio in liver cirrhosis than in chronic hepatitis. The existence of shunts and the poor increase of the cardiac index in response to dobutamine explained the limited improvement of portal blood flow velocity in cirrhosis patients. The ketone body ratio was improved by dobutamine in cirrhosis patients whose portal blood flow velocity was increased by more than 10%, while this ratio decreased when the increase of it was less than 10%. There was no change in portal oxygen extraction in the cirrhosis group, and portal oxygen uptake only increased when the portal blood flow velocity rose by more than 10%. Dobutamine should only be used to treat liver failure if the portal blood flow velocity is increased by more than 10% or the arterial ketone body ratio is improved by a test infusion.     

Respiratory mechanics in brain injured patients

BACKGROUND: Brain injured patients have an increased risk of extracerebral organ failure, mainly pulmonary dysfunction. The prevalent cause of pulmonary failure is ventilator associated pneumonia (VAP) which increases morbidity and mortality. The respiratory dysfunction is mainly characterized by the presence of alveolar consolidation of the dependent lobes. METHODS: We investigated the mechanical changes of the respiratory system and the effects of positive end-expiratory pressure (PEEP) in 10 normal subjects, in 10 brain injured patients without respiratory failure and in 10 brain injured patients with respiratory failure (PaO2/FiO2 lower than 200 mmHg) due to VAP. RESULTS: We found that: 1) Intra-Abdominal Pressure (IAP) was increased in brain injured patients with or without respiratory failure compared to normal subjects; 2) the Elastance of respiratory system (Est,rs), the Elastance of the chest wall (Est,cw) and Resistance max of the Lung (Rmax,L) increased in brain injured patients independently from the presence of respiratory failure; 3) in brain injured patients with respiratory failure application of 15 cmH2O of PEEP increased the Elastance of the Lung (Est,L), Est,rs and Rmax,L, while did not result in significant alveolar recruitment and oxygenation improvement. CONCLUSIONS: In conclusion, in brain injured patients 1) the respiratory mechanics is altered; 2) PEEP is uneffective to improve respiratory function in respiratory failure due to ventilator associated pneumonia. Further studies are warranted to better elucidate the pathophysiology and clinical management of respiratory dysfunction in brain injured patients.     

HISTOLOGICAL STUDY OF CONGENITAL and ACQUIRED CYTOMEGALOVIRUS INFECTION

Of 180 autopsied cases in children, of which 85 infants were less than one month of age, seven cases of cytomegalovirus infection are described here. Two patients died of congenital cytomegalovirus infection with generalized cytomegalic inclusion disease and one of them was associated with leukemoid mononucleosis. Five cases, 2,8 per cent of 180 cases, were acquired cytomegalovirus infection with localized lesions of cytomegalic cells in the lungs, incidentally found at postmortem examination. The youngest case of acquired cytomegalovirus infection was one month of age. These spontaneous pulmonary infectious changes early in life, associated occasionally with cytomegalic cells in the vascular wall, may suggest that the lung is one of the initial sites of the acquired cytomegalovirus infection preceeding viruria or elevation of antibody titer at later period of life.     

Hypoproduction of erythropoietin contributes to anemia in chronic cadmium intoxication: clinical study on Itai-itai disease in Japan

Itai-itai disease is a condition caused by longterm exposure of the inhabitants of Toyama prefecture, Japan, to cadmium intoxication. The characteristic clinical features of this disease include renal tubular dysfunction, osteomalacia, and anemia. In order to clarify the pathogenesis of the anemia, the red blood cell count, hemoglobin concentration, hematocrit, serum iron level, total ironbinding capacity, serum ferritin level, serum erythropoietin level, creatinine clearance, fractional excretion of β₂-microglobulin, and bone marrow morphology were determined in ten patients with Itai-itai disease. Low serum iron or ferritin levels were not observed, and bone marrow aspiration did not reveal any specific hematological disorders. A close relationship was observed between the decrease in the hemoglobin level and the progression of renal dysfunction. Low serum erythropoietin levels were detected despite the presence of severe anemia. These results suggest an important role of renal damage in the anemia which develops in Itai-itai disease.     

Taurine conjugate of ursodeoxycholate plays a major role in the hepatoprotective effect against cholestasis induced by taurocheno-deoxycholate in rats

ABSTRACT— Rats which were taurine-deprived through ß-alanine administration and untreated rats were used to elucidate the mechanism of hepatoprotective effects of ursodeoxycholate (UDC). Animals were infused with taurochenodeoxycholate (TCDC, 0.4 μmol · min^-1 · 100 g^-1) alone or in combination with tauroursodeoxycholate (TUDC), or with UDC (both 0.6 μmol · min-1 · 100 g^-1) for 2 h. Ursodeoxycholate as well as TUDC prevented severe cholestasis and liver damage induced by TCDC infusion in both untreated and taurine-deprived rat groups. In untreated rats, however, UDC was less effective in hepatoprotection than TUDC as indicated by sequential changes in biliary LDH output during the period of 30 to 120 min (P<0.05). In rats receiving UDC and TCDC, total biliary output of LDH for 2 h was significantly higher in taurine-deprived rats than that in the control (73.40±10.10 vs 41.14±12.56: P < 0.05), suggesting that the difference became greater upon taurine deprivation. In contrast, in rats receiving TUDC and TCDC, the protective effect was comparable for the taurine-deprived and untreated rats. When the animals were infused with UDC and TCDC, taurine-deprived rats exhibited a biliary excretion rate for TUDC half that of control rats (P<0.05). Furthermore, a highly significant correlation was observed between the biliary excretion rate of TUDC and biliary output of LDH (r = –0.886, P<0.0001). These results suggest that UDC conjugates, especially TUDC, and not UDC may play a major role in the prevention of cholestasis and liver cell damage caused by TCDC infusion.     

Diaphragmatic Hernia Induced in Rat Fetuses by Administration of Bisdiamine

Administration of N, N'-bis (dichloroacetyl)-l,8-octamethylenediamine, bisdiamine, to pregnant Donryu rats on a single day of gestation induced unilateral and bilateral diaphragmatic hernias in fetuses with high incidence. The protruded liver was not covered with a serous membrane or a muscular layer. Incidence of unilateral diaphragmatic hernia on the left side was high when bisdiamine was administered on day 9 or 13 of gestation, and that on the right side was high when administered on day 12 of gestation. Incidence of bilateral diaphragmatic hernia was high when bisdiamine was administered on day 12 of gestation. Differences in sensitivity to hernia formation according to day of bisdiamine administration between right and left sides may reflect differences in developmental chronology between the two sides. Two distinct times for induction of left diaphragmatic hernia might be attributed to at least two different mechanisms. The present model is expected to help analyzing not only anatomical characteristics of congenital diaphragmatic hernia but also possible mechanisms responsible for their development.     

Correlation of Active Folate Availability with Effects of Folic Acid on Pyrimethamine Teratogenesis in Rats

Oral administration of pyrimethamine (PYR) 3.6 mg/kgBW/day to the pregnant rats from day 11 to day 15 of gestation caused malformations in all the fetuses, but concomitant intraperitoneal administration of folic acid (ip FA) 50 mg/kg/day inhibited the incidence of malformations by 25%. On the other hand, the same dose of oral FA (in feed) had an opposite effect on PYR teratogenesis; the incidences of malformed fetuses were 0% in the PYR 1.6 group, but 100% in the PYR with oral FA group. The plasma levels of 5-methyltetrahydrofolic acid (5MF), a principal transfer form of folate, were measured after single oral administration of PYR with or without FA (ip or oral) in non-pregnant female rats. The area under the plasma concentration-time curve (AUC) after the concomitant administration of PYR with ip FA was larger than that after PYR alone. This result indicated that the available 5MF for the peripheral tissues was increased by the concomitant administration of ip FA. The AUC after the concomitant administration of PYR with oral FA was smaller than that after PYR alone. These results suggested that ip FA increased the available 5MF to ameliorate, but oral FA decreased the availability to aggravate the PYR teratogenesis.     

SIGNET RING CELL CARCINOMA IN A POLYP OF THE COLON

Undifferentiated adenocarcinoma of the colon occurring in a 6-year-old boy was presented. The tumor characterized by the signet ring cell appearance developed in a polyp of the descending colon. The signet ring cell carcinoma is in general a rare morphologic form of colonic carcinoma. According to our review of the literature there have been described 16 patients under 10 years of age with colonic or rectal carcinoma, disclosing 2 cases of undifferentiated or signet ring cell carcinoma including the present case. In children, mucin producing adenocarcinoma is the most predominant type of colonic carcinoma, and 48% of the colonic carcinomas are of signet ring cell carcinoma in children under 17 years of age.