The role of cathepsin D in pathogenesis of acute post-streptococcal glomerulonephritis. Cathepsin D activity has been studied by a fluoremetric assay in the urine of acute post-streptococcal glomerulonephritic (APSGN) patients aged from 3 to 14 years and has been found elevated when compared with four groups of controls. This activity cannot be accounted for by erythrocytes and/or leukocytes in the urine of these patients since haematuric and pyuric controls did not exhibit an amount of enzyme activity greater than the normal control group. Cathepsin D activity can be attributed to lysosomal enzymes released from polymorphonuclear leukocytes which are in close contact with glomerular basement membrane. Complement C3 levels in serum and cathepsin D activity in urine of these patients showed no correlation.


The role of haemolysis in neonatal hyperbilirubinaemia as reflected in carboxyhaemoglobin levels. Carboxyhaemoglobin levels were measured in 250 consecutive, normal, term newborns and in a group of 75 severely jaundiced infants in an effort to assess the role of haemolysis in non-specific neonatal hyperbilirubinaemia--"Physiologic jaundice"-as well as in severe jaundice of various etiologies. In normal newborns a significant correlation (r=0.3293, p less than 0.001) was found between third-day carboxyhaemoglobin and serum bilirubin levels. Significant correlations were also found between the cord and third day values for carboxyhaemoglobin (infants of non-smoking mothers) for reticulocyte count, and for serum bilirubin. Third day haemoglobin showed no correlation with any of the other parameters including cord haemoglobin. Of the infants with third day carboxyhaemoglobin up to 0.75%, 1.7% had third day serum bilirubin values above 16.0 mg/100 ml. The corresponding percentage for the infants with carboxyhaemoglobin above 0.75% was 6.1%. It is concluded that increased rates of haemolysis due to as yet unspecified caused play an important role in the non-specific hyperbilirubinaemia of normal term newborns. As expected, high levels of carboxyhaemoglobin were found in infants with severe jaundice due to Rhesus and ABO haemolytic disease and glucose-6-phosphate dehydrogenase deficiency but also in jaundiced prematures and in Greek infants with severe jaundice of unknown cause.


Treatment of idiopathic autoimmune hemolytic anemia in children. Review and report of two fatal cases in infancy. Report of two cases of severe idiopathic autoimmune hemolytic anemia (AIHA) in infants who underwent splenectomy and received corticosteroids and cyclophosphamide without benefit. One infant, additionally, was treated with thymectomy and azathioprine without influencing his disease. Experience of therapy for childhood AIHA is reviewed. Four children with AIHA have been thymectomized. Two of these failed to benefit from surgery. There have been fifteen previous trials with immunosuppressive agents in childhood AIHA. About 60% of the children so treated (9 of 15) have shown improvement. Additional clinical trials with this agent are warranted.


Familial occurrence of cerebral gigantism, Sotos' syndrome. Since the original description of cerebral gigantism, about 85 cases have been reported. Four papers comment on familial occurrence but never in parents and their children. This paper describes the syndrome in a mother and her child, which, together with facts pointing towards prenatal etiology, such as excessive birthweight, striking mutual resemblance and abnormal dermatoglyphics, points to a genetic defect. Previous endocrine studies are enlarged by the findings of normal serum somatomedin and serum prolactin.


Unstable-haemoglobin haemolytic anaemia. A 6-year-old girl suffering from chronic haemolytic anaemia with crisis induced by drugs and infections is described. The disorder was diagnosed as an unstable-haemoglobin haemolytic anaemia. The heat stability test, simple and specific for unstable haemoglobins is mentioned, it should be done in every child suffering from unexplained chronic haemolytic anaemia. The haemoglobin variant is also known in a patient in Brazil as Hb Niteroi.


An ultrastructural study on precancerous and cancerous lesions of the glandular stomach in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine. Electron microscopic study was made on precancerous and cancerous lesions in glandular stomach of rats induced by MNNG. Three types of lesions, were found: regenerative glandular hyperplasia, adenomatous hyperplasia  and adenocarcinoma. These were compared with the fine structure of similar lesions produced by X-irradiation in the glandular stomach of mice. The precancerous lesion in the present study demonstrated formation of adenomatous hyperplasia by epithelial cells which included mucoid cells characterized by sparce surface microvilli, a few erratic terminal webs, small number of mucous granules, many small mitochondria, and a bizarre nucleus. The development of these mucoid cells seems to be related with the growth of gastric carcinoma. The ultrastructure of adenocarcinomas revealed many structural variations or abnormalities of cellular differentiation. They were classified into 1) surface and pit mucous cell type, 2) pyloric gland cell type, 3) goblet cell type, 4) paneth cell type, 5) intestinal epithelial cell type, 6) endocrine cell type, 7) oncocyte type, 8) filament-rich cell type, and 9) anaplastic cell type involving intracellular microcyst cells. Filament-rich cells were found in poorly differentiated adenocarcinoma or scirrhous carcinoma and may be derived from metaplasia of tumor cell.


Abnormal intracranial vascular networks ("moyamoya" disease), possibly due to occlusion of bilateral internal carotid arteries--a case report with histometrical analysis. An autopsy case of abnormal intracranial vascular networks at the base of the brain corresponding to so-called rete mirabile, associated with occlusion of bilateral internal carotid arteries was reported. This patient was a 62 year-old female who died about two months after sudden onset of subarachnoid hemorrhage. At autopsy, abnormal vascular networks termed as rete mirabile were observed to be collateral blood supplies among the cerebral regions with flow of the anterior, middle, and posterior cerebral arteries, caused by long-standing obstruction of bilateral internal carotid arteries at the syphon level. Morphometrical analysis was done by measuring the length of internal elastic membrane of the internal carotid arteries in cross section, and comparing it with those of controlled persons of the same sex and age without any intracranial disorders and hypertensive histories. The result that no significant difference was observed between the former and the latter values suggested that the unusual cerebro-vascular disorder of this case developed not on the base of congenital anomaly including hypoplasia of internal carotid arteries or arteriovenous malformation but as an acquired lesion established for a long time.


Ultrastructure of the giant cell in de Quervain's subacute thyroiditis. The author made an electron microscopic observation on multinucleated giant cells which appear in the thyroid gland in subacute thyroiditis (de Quervain). Numerous typical desmosomes, which intermingled with myriad of mitochondria and small electron dense granules, were found in the cytoplasm of giant cell. Desmosome is one peculiar to the intercellular junction of follicular epithelium of the thyroid gland, and the fact that many desmosomes were found in the cytoplasm is one of the proofs showing this giant cell to be possibly derived from the follicular epithelium.


Histological study on the numerical change of plasma cells in regional lymph nodes of the carcinomatous stomach. The relationship between metastatic lesions and the degree of appearance of plasma cells in regional lymph nodes affected by carcinoma of the stomach was observed in this study. At the initial stage of metastasis to a lymph node, numerous plasma cells were found in tje lymphatic parenchyma adjacent to the metastatic lesion. As the metastatic lesions increased, the number of plasma cells decreased. Few plasma cells appeared in the intact lymph node distant from the primary lesion of carcinoma. It is suspected that this phenomenon may be tentatively explicable from  the antigen-antibody reaction at the initial stage of metastasis in a lymph node.


A histopathological study on diabetic nephropathy -- light and electron microscopic observations. A historical review and the present author's study on diabetic nephropathy have been presented. Three characteristic lesions in KW-lesion, namely nodular, exudative and doughnut lesion may all be regarded as to be caused by severe circulatory disturbance occurring in intraglomerular branches of the afferent artery. This circulatory disturbance is considered to be brought about by sudden spasm of the peripheral portion of the afferent branches. The diffuse form of Bell may be regarded as to be a slighter type without severe mesangiolysis. Arteriolar hyalinosis and arteriosclerosis and/or atherosclerosis may be caused by intraglomerular circulatory disturbances. The most important problem in diabetic nephropathy, including KW-lesion and Bell's diffuse form, is to elucidate the mechanism leading to the occurrence of spasm of the peripheral portion of intraglomerular afferent branches. Becker found fixation of antiactomyosin-antibody in the mesangial tissue by the immunofluorescent method. Many studies along this line have been made, but none are adequate in fully explaining the mechanism involved.


Inhibition of senile amyloidosis of mice by biscarboxyethyl germanium sesqui-oxide. A mouse strain, ICR/SLC, was involved in spontaneous amyloidosis with high incidence. The amyloid deposition in this strain was seen mainly in the mucosal propria of duodenum and terminal ileum, liver, spleen, adrenal cortices, and renal glomeruli. The mice, orally administered more than 300 mg/kg of organic germanium for 22 months since 5 weeks old, did not develop amyloidosis. Half of the mice, given 30 mg/kg of organic germanium  for 22 months developed amyloidosis. The mice given 5% carboxymethylcellulose, the solvent of organic germanium, were affected with systemic amyloidosis with high frequency. The results showed that the organic germanium successfully inhibited the occurrence of senile amyloidosis with dose response. The agent did not have any apparent relation to the incidence of hepatic cell carcinoma or pulmonary adenoma which is frequently combined with aged mice. Although the actual mechanism involved is not clear, the evidence of the inhibition of senile amyloidosis by organic germanium may give a light to elucidate the pathogenesis of amyloidosis.


The role of coagulation and fibrinolysis in the development of rabbit Masugi nephritis. The role of coagulation and fibrinolysis in the pathogenesis of rabbit Masugi nephritis was studied. Fibrinolytic activity of urine decreased rapidly to the minimum values at the peak of the disease. Histologic observations showed a severe proliferative glomerulonephritis. Immunofluorescent studies revealed localization of rabbit gamma globulin along the glomerular basement membrane in a typical linear pattern. Fibrin was positive in glomeruli not only within fibrinoid deposits, but also often diffusely in the places where no obvious fibrin was detected in histologic sections. Bright strands of fibrin was present between the cells forming a cresent. Electron microscopy indicated accumulation of fibrinoid materials beneath the endothelium. The basement membrane was damaged by the deposition of fibrinoid and followed by massive escape of intracapillary contents into the Bowman's space. Abundant fibrin and fibrinoid were seen in newly formed "monocytic-epithelial" crescents. Todd's fibrinolysis autography revealed diminished fibrinolytic activity in the severely affected glomeruli. Treatment with heparin prevented crescent formation and glomerular disorganization, while treatment with t-AMCHA increased fibrin and fibrinoid deposition and aggravated the glomerular injuries. It was concluded that the coagulation-fibrinolysis system could play an important role in the course of rabbit Masugi nephritis.


Ultrastructure of the "non-pathologic" human pituitary gland. The ultrastructure of "non-pathologic" human pituitary gland obtained from eight cases at autopsy, who received no hormonal therapy and who revealed no significant changes in the pituitary and its target organs, was investigated in an attempt to identify human adenohypophyseal cells by comparing their secretory granules with those of experimental animals. Besides the follicular cell, five different granulated cell types were distinguished The Type 1 cell contained abundant, dense secretory granules (350-500 mmu across). The Type II cell was characterized by dense granules, which were the largest in size (500-700 mmu across) and the most irregular in shape. Granules of the Type III cell were less characteristic (200-300 mmu across). The Type IV cell contained dense granules, which were the smallest in size (100-150 mmu across) and were characteristically arranged along the plasma membrane. The Type V cell was characterized by the presence of small, haloed granules (100-200 mmu across). The cells of these five types could presumably be the somatotroph, lactotroph, gonadotroph, thyrotroph and corcitotroph, respectively.


Enzyme histochemical observations of diffuse pulmonary fibrosis of rats experimentally induced by ionizing irradiation. The right lungs of Sprague-Dauley rats were irradiated with single doses of 1000 r, 2000 r or 3000 r to induce radiation pneumonitis and diffuse fibrosis, and the alkaline and acid phosphatase (A1-Pase, Ac-Pase) activities of the lungs were observed histochemically. Only the lungs irradiated with 3000 r steadily exhibited sequential changes leading to radiation pneumonitis and subsequent diffuse fibrosis, whereas the lungs irradiated with 2000 r developed only some degree of radiation pneumonitis. Alveolar capillary endothelia in the lesion of pulmonary fibrosis exhibited an intense activity of A1-Pase, while the endothelia in all the other experimental conditions did not show this activity. Alveolar macrophages increased their sizes and the activity of Ac-Pase after the irradiation. In the later stages, large foamy macrophages with thin diffuse deposits of the reaction products became predominant. These macrophages never exhibited A1-Pase activity. Type II alveolar epithelial cells showed an intense A1-Pase activity on their microvilli, and their Ac-Pase activity was negligible in non-irradiated lungs. Bizarre cells, appearing at the stage of radiation pneumonitis, showed an intense A1-Pase activity on their cell membranes and a weak and diffuse Ac-Pase activity in their cytoplasms. Septal cells achieved the A1-Pase activity 3 or 4 weeks after the irradiation when mast cells were not yet seen in the alveolar septa.


Two autopsy cases of primary adenoacanthoma of the stomach. The incidence of primary adenoacanthoma of the stomach is extremely low. In the Sasebo City Hospital, there were only two autopsy cases of adenoacanthoma among 46 cases of gastric cancer during the past four years. The first case was a 45-year-old female with metachronous triple cancers; adenoacanthoma of the stomach, squamous cell carcinoma of the uterus and squamous cell carcinoma of the tongue. Histological examination showed muconodular adenoacarcinoma of the stomach at the time of first operation and adenocanthoma at the time of autopsy. These two cases suggest that adenoacanthomas of the stomach may originate from squamous metaplasia or squamous differentiation of a preexisting glandular carcinoma.


Mesenchymal hamartoma of the liver--an autopsy case with serial sections and some comments on its pathogenesis. An autopsy case of mesenchymal hamartoma of the liver was reported and from the macroscopical observation and serial sections of the tumor the following findings were found: (1) macroscopically the tumor is supplied by only one large triad, (2) in the tumor hepatic lobular structure is fundamentally preserved and prolifereated bile ducts with surrounding fibrosis and many bile thrombi are mainly elongated and dilated Hering's canals, (3) the cysts connect with dilated interlobular bile ducts, (4) there are two portions, where connection of bile ducts is incomplete, that is, from Hering's canals to interlobular bile ducts and from interlobular ducts to large ducts in the large triad of (1), (5) almost all portal veins in the large triad of (2) are stenosed or obliterated by loose intimal fibrosis. From these findings it is considered that intrahepatic bile duct obstruction resulting in regional biliary cirrhosis is the fundamental process of this disease, and in addition the role of hemodynamic disturbance was discussed.


Membranous glomerulonephritis associated with active liver cirrhosis both involved by HBs antigen. This is a case report of a 35-year-old female who showed a relatively short clinical course of severe liver cirrhosis and proteinuria. On light microscopical studies of autopsy material, besides active postnecrotic type liver cirrhosis, typical membranous glomerulonephritis was found. Immunofluorescent study disclosed not only clustered HBsAg (hepatitis type B surface antigen) in occasional hepatic cells but also beaded granular type deposition of HBsAg, IgG, IgM, IgA and complement C3 along renal glomerular basement membrane (GBM). Electron microscopical study disclosed multiple particulated material in occasional inclusion bodies of hepatic cells and in subepithelial and subendothelial dense deposits along the GBM. Enzymatic immunoelectron microscopical study confirmed these particles especially along the GBM being HBsAg themselves. It was concluded that HBsAg-Ab (antibody) complex was the pathogenetic factor responsible for the glomerular change of this particular case. Although HBsAg and Ab were examined to be negative in serum throughout the patient's clinical course, the possibility of the presence of circulating HBsAg-Ab complex in serum was discussed.


Myositis ossificans progressiva with parathyroid hyperplasia and polycystic ovary. A report was made on an autopsy case of myositis ossificans progressiva in a girl who died at the age of 8 year and 11 months. The first symptom appeared as right wryneck ten days after birth. Parathyroid hyperplasia and polycystic ovary with high level of serum parathyroid hormone, FSH and LH were confirmed at autopsy. Parathyroid hyperactivity might be a secondary response to the continuous stimulation by increased peripheral consumption of calcium ions due to relentlessly progressive ossification in fibrous connective tissue.


Congenital brain and facial anomalies in the D1 trisomy syndrome--report of a case and a review of literature--. On 58 cases of D1 trisomy, which were classified as those with seven separate D chromosomes, including the one in this report, congenital brain and facial anomalies were reviewed and discussed. Congenital brain defects in this syndrome might be classified into three groups: (I) grossly normal brain, (II) absence of olfactory bulbi and tracts, but normally-separated cerebral hemisphere, and (III) completely or incompletely uncleaved hemispheres with absence of olfactory bulbi and tracts. 25.9% of the cases were found in group I, 56.9% in group II, and 17.2% in group III, respectively. Although facial anomalies predicted the brain defects in group III, malformations of the face were not concerned with the brain defects in group I and II. There were no cases with both, normal brain and face.


Increase in the amount of nuclear RNA in liver of ascites tumour-bearing mice. The effect of tumour growth on the liver of the host was studied in the Ehrlich ascites tumour system. During the experimental period there was no infiltration of tumour cells in the liver, and the increase in the proliferation rate of Kupffer cells and parenchymal cells was only small. An increasing stability of the liver cell nuclei towards disruption during the isolation procedure was found to accompany the ascites tumour growth. In parallel, there was an increase in the amount of nuclear RNA and in the cellular speridine concentration. The major cause of these changes is probably an increasing demand on the liver by the growing tumour, illustrated by the fact that an amount of protein exceeding that of the whole liver accumulates in the ascites fluid during tumour growth. A hypothesis according to which the cellular accumulation of spermidine may be involved in the stabilization of cell nuclei and in the accumulation of nuclear RNA is advanced.


The role of thymus for the development and prognosis of hypertension and hypertensive vascular disease in mice following renal infarction. Partial infarction of one kidney and contralateral nephrectomy was followed by a rapid and significant increase in blood pressure both in haired mice with a normal thymus function and in nude mice with genetical aplasia of the thymus. The level of blood pressure and the prognosis were not influenced by the presence of thymus within the first 3 months after partial infarction of the kidney; but a significantly more pronounced increase in blood pressure after 4 months was observed in a small group of haired mice than in a similarly treated small group of nude mice. A marked degree of round cell infiltration around intrarenal arteries was only found in the haired mice, commencing 2 months after partial infarction of the kidney. Degenerative changes were observed in the kidneys of the haired mice 2-4 months after infarction. Very few of these lesions were found in the nude mice. Atempts to transfer the hypertension by means of viable lymph node cells from hypertensive donors to normotensive syngeneic recipients failed. The results support the assumption that high intravascular pressure induces thymus-dependent immune reactions against substances in teh vascular walls which, in turn, may have a prognostic significane; the results give no support for the assumption that the earlier phase of the hypertension which follows partial infarction of the kidney and contralateral nephrectomy is thymus-dependent.


Cronic non-rheumatic valvular heart disease. An autopsy study. The frequency of chronic non-rheumatic valvular heart disease in Iceland was investigated via autoposies performed from November 1965 through December 1974. During this period, about 12.400 Icelanders died at the age of 16 years and older and 28.8 per cent of these were included in the study. At autopsy, males outnumbered females by 2:1. The frequency of calcific aortic stenosis was found to be 3.63 per cent and the prevalence was calculated to be 3.17 per cent among males and 4.50 per cent among females. Calcific aortic stenosis in tricuspid valves was more frequent in females and calcific aortic stenosis in bicuspid valves was more frequent in males. Among the hearts with calcific aortic stenosis, 70.8 per cent were found to have normally tricuspid valves, 25.4 per cent bicuspid valves and 3.8 per cent tricuspid valves with an unicommissural fusion. In 0.59 per cent of the hearts the aortic valve was either bicuspid or had an uncommissural fusion without the features of calcific stenosis. However, a functional stenosis was suggested by the increased weight of most of these hearts. The frequency of bicuspid aortic valves was 1.2 per cent with a prevalence in males of 1.54 per cent and in females 0.50 per cent. A calcified mitral annulus was found in 1.98 per cent of the hearts and in most, it was either associated with calcific aortic stenosis in a tricuspid valve, or it was a single valvular disease. Rheumatic valvular disease was found in 1.08 per cent of the heart examined.


Liver biopsies from psoriatics related to methotrexate therapy. 1. Findings in 123 consecutive non-methotrexate treated patients. A prospective study was started in 1969 to describe morphological features of liver biopsies from patients with severe psoriasis. Among 123 patients evaluated for possible MTX therapy, liver biopsies disclosed pathological histology (maninly fatty change and/or non-specific reactive hepatitis) in 51 per cent. The incidence of pathological liver histology did not statistically correlate with psoriasis parameters such as duration and extent. However, statistically significant correlations (p less than 0.0001) were found between the frequency of pathological liver histology and other factors such as age, obesity, and daily alcholic intake. Comparison of liver histology with SGOT value at the time of liver biopsy showed that while the diagnostic specificy of this test high (1.00), the diagnostic was low (0.17). Normal values of SGOT should not be relied upon to indicate all types of liver pathology. A "risk index" indicating the probability of pathological liver histology was developed. It is calculated as follows: two times the height (cm) minus weight (kg) minus age (years) minus 50 (in case of daily alcoholic intake) minus 50 (in case of elevated SGOT). To elucidate liver histology and particularly to rule out fibrosis and cirrhosis, a liver biopsy should be performed in every psoriatic patient with a low score in the risk index prior to beginning MTX therapy.


Liver biopsies from psoriatics related to methotrexate therapy. 2. Findings before and after methotexate therapy in 88 patients. A blind study. Eightyeight patients with severe, recalcitrant psoriasis had liver biopsies performed before and after Methotrexate (MTX) therapy. MTX was given for an average of 26 months as a single, weekly, oral dose of 25 mg maximum. The mean cumulative dose was 1733 mg (range 175-4590 mg). A statistically significant increase in the number of pathological post-MTX liver biopsies was found (p less than 0.0001). Of the 88 patients 6 developed cirrhosis and another 5 developed fibrosis, in all 12.5 per cent, during MTX therapy (95 per cent confidence limits for cirrhosis: 3-14 per cent). There was no statistically significant correlation between the number of pathological post-MTX liver biopsy findings in the 88 patients and the following variables one by one: cumulative dose of MTX, duration of MTX therapy and admitted alcoholic intake during MTX therapy. Cirrhosis and fibrosis did not develop statistically more frequently from pathological than normal pre-MTX liver histology (p = 0.062). The liver damage appeared to be due to a multifactorial interaction of straining factors on the liver during MTX therapy. A multifactorial index comprising: cumulative dose of MTX, admitted alcoholic intake during MTX therapy, age, obesity and, if available, pre-MTX liver histology gave an estimate of the probability of developing cirrhosis or fibrosis during treatment of psoriasis with weekly, oral doses of MTX. For use of MTX therapy in psoriasis  the following precautions are suggested: MTX therapy should be used only in disabling cases; a pre-MTX liver biopsy and repeat liver biopsies at regular intervals of 1/2-1 year should be performed, alcohol should be prohibited and frequent inquiries should be made about the patient's alcoholic intake; and strong reliance should not be placed on the SGOT as an indicator of abnormal liver histology.


Bile canalicular alkaline phosphatase in necropsy specimens of the liver and its relation to disease. The histochemical patterns of the alkaline phosphatase reaction in liver specimens obtained at 185 consecutive autopsies were studied for any correlation with clinical data and post mortem findings. Alkaline phosphatase activity of bile canaliculi was found in 71 per cent of the subjects with malignant tumours not involving the liver, and in 77 per cent of the subjects with malignant tumours involving the liver. The histochemical pattern did not differ with the type of tumour. Most subjects with rheumatoid arthritis as well as most of those with centrolobular hepatic necrosis due to heart incompensation also showed alkaline phosphatase activity in the bile canaliculi.


Vast and apparently paradoxical continuous rise in plasma renin after removal of gently manipulated submaxillary glands in nephrectomized mice. Gentle manipulation of the submaxillary glands of previously nephrectomized mice results in a vast increase in plasma renin concentration. The concentration reaches 1 to 7 G.U. renin/ml, which is 1,000-fold higher than normal plasma concentrations. The rise is much less pronounced if the glands are removed after the manipulation, confirming the site of the release. However, an apparent paradox is seen: the renin concentration continues to rise even after removal of submaxillary glands as well as kidneys, indicating that a bound a form of renin is also released. The bound renin can be in the form of exocytosed granules or (and) in the form of "protein", the renin of which is activated with time. In spite of the very high renin concentrations the blood pressure is normal or only moderately increased. This disproportion between plasma renin and blood pressure can be caused by a simultaneous release of submaxillary kallikrein and renin, which have conteracting effects on the blood pressure.


Enterotoxin, haemolysin and cytotoxic protein in Aeromonas hydrophila from human infections. Three different toxins were detected in culture supernatants from 11 strains of Aeromonas hydrophila. The haemolysin and the cytotoxic factor(s) interferred in the three test systems for enterotoxin, but they could be neutralized by heating at 56 degrees C or by specific antihaemolysin.


The effect of acute rise in intracranial pressure on the sympathetic cardiac, vertebral and phrenic nerve activities. A transient rise of intracranial pressure in cats under chloralose-urethane anaesthesia increased the activity of the sympathetic vertebral nerve, cardiac nerve and in the first phase phrenic nerve. If the vagus nerves were intact this rise in sympathetic activity was associated with bradycardia. These effects developed with a delay, as a rule after abatement of the transient intracranial pressure rise. The authors suggest that Cushing's reaction is caused by medullary ischaemia and development of local metabolic acidosis activating simultaneously the sympathetic and parasympathetic neurons in the medulla oblongata.


Lack of stimulating effect of hypertonic Nacl intravenous injection on the release of melanocyte-stimulating hormone from the hypothalamic end of the cut pituitary stalk. After removal of the whole pituitary gland in the rat, intravenous injection of 5% NaCl solution (0.5% of body weight) had no effect on MSH release from the washed hypothalamic end of the cut pituitary stalk and the ventral surface of the median eminence.


A method of evoking fast baroreceptor responses for the measurement of the baroreflex latency. A method for measurement of latency in the baroreflex is described. Standardised square pressure pulse was applied to the isolated carotid sinus and simultaneous recordings of the carotid sinus nerve or sympathetic fibers were performed. Relatively short time of the increase of the pressure makes possible more exact measurements of latency in the baroreflex than other known methods used for this purpose.


Effects of acetylcholine and other vasodilatory substances in the vascular bed of skeletal muscles during and after muscular contractions. In dogs and cats perfusion pressure or femoral venous outflow and changes in the volume of the hind limb were measured. The influence of muscular contractions on the effects of acetylcholine, histamine, isoprenaline and papaverine in the vascular bed of the limb was investigated. It was found that after muscular excerise the effects of i. a. injection of acetylcholine into the isolated limb were markedly potentiated, whereas the effects of histamine and isoprenaline were diminished.


Effect of propranolol on thyroxine-induced changes in body temperature and metabolism during exercise in dogs. Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s.c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (Tre) during exercise as early as 5h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest Tre, blood FFA and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in Tre and blood LA concentrations during the next 30 min of exercise.


The effects of bradykinin on electrobiological phenomena in isolated right atrium of the rat. Bradykinin induces or accelerates the already present electrobiological activity in isolated right atrium of rats. Acceleration of the electrobiological activity induced by bradykinin decreases with increase of initial activity. Bradykinin disturbs transiently the course of the repolarization period in action potential. It may be one of the mechanisms of arrhythmia development caused by bradykinin.


Effect of physical training on the permeability of vascular bed to albumin labelled with T-1824. Two-week physical training caused in dogs a rise in vascular permeability by 40--50% persisting for at least 24 hours after the last run. Simultaneously, the obtained results point out that physical training leads to increased production and flow of lymph and to increased turnover rate of substances between the intra- and extravascular spaces in the animals at rest.


Experimental studies on osmotic mechanisms and vegetative regulations of intraocular hydrodynamics as well as the distribution of elecrolytes and amino-acids in refractive environments of the eye. The studies were carried out on the influence of hyperosmolar loading with glycerol and hypoosmotic glucose, as well as on the effect of pharmacological stimulation of the adrenergic system after sympathetic decentralization of the eyes, and of the cholinergic stimulation, on intraocular hydrodynamics, and on the distribution of electrolytes and amino-acids in refractive environments. The results showed a dependence between the changes in blood osmolality and osmotic intraocular activity, and the secretion and flow of the aqueous humor, as well as the distribution of electrolytes and amino-acids. No specific, antagonistic influence of the adrenergic and cholinergic stimulation on the hydrodynamics and the distribution of electrolytes and amino-acids in refractive environments has been found. The opposite reactions to stimulation of adrenergic alpha or beta-receptors have been observed.


The post-exercise glycogen recovery in tissues of trained rats. The post-exercise glycogen recovery in myocardium, liver, diaphragm muscle and musculus biceps femoris was compared in untrained and trained rats. The glycogen level in myocardium of the trained rats was significantly higher than that in the untrained ones only immediately after the exercise-test and on the second day after the exercise. The liver glycogen levels on each of the examined post-exercise days were similar in both groups and did not differ from the control values. The post-exercise glycogen recovery in the diapraghm muscle of the untrained rats was also similar to that in the trained animals. In musculus bicpes femoris similar post-exercise supercompensation was found in both groups except on the second day when the glycogen level in the trained animals was significantly higher than that in the untrained ones. The results suggest that it is necessary to separate the effects of training from those of the last bout of exercise in the training program when the effect of training is examined.


Neural control of breathing: a system analysis. A model of the neural control of quiet breathing in an anaesthetised and tracheostomised laboratory animal is presented. The loop consisting of the brain generator with its respiratory "master function", the phrenic command, the aerodynamics of the lungs and the volume information carried by the vagus nerves is described in mathematical terms. Computer model experiments are presented and compared with corresponding physiological situations. The stability of the model is demonstrated.


A decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise in dogs. The aim of the investigations carried out on dogs was to elucidate possible causes of the decreased hyperglycemic response to adrenaline after exhausting exercise. The k-values of i.v. glucose tolerance tests were calculated and the dose-response relationship to infused adrenaline was analyzed under control, resting conditions, and after exhausting exercise. K-values (KG-exc.) were significantly higher (p less than 0.01) after exercise than in control experiments, whereas hyperglycemic responses to the applied doses of adrenaline: 0.25, 0.5, 1.0, 2.0 and 3.0 mug-kg-1min-1 were considerably lower. In both situations a linear relationship was found between the hyperglycemic response and the dose of adrenaline, although the slope of the regression line, expressing this relationship, was significantly lower after exercise than that under control conditions. It is suggested that the decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise may be attributed to both the increased rate of glucose elimination from blood, and a decreased responsiveness of the liver to adrenaline.


An influence of exercise of increasing intensity on aminotransferase activity and electrolyte level in red blood cells and blood serum in men with average and very high physical working capacity. Healthy subjects with average and very high physical working capacity were submitted to two 6-min periods of work on a cycloergometer at the work loads 70 and 90 percent VO2max. Changes in the activity of Asp AT and Al AT as well as in the concentrations of NA, K and lactates in erythrocytes and serum were determined. In the subjects with average physical working capacity the serum concentrations of lactate and sodium, as well as the activity of Asp AT were much more increased than in the highly efficient subjects. In both groups similar changes of electrolyte concentrations in erythrocytes occured. The activity of Al AT was increased only in the group of subjects with high physical working capacity after the first period of work and showed a tendency to return to the resting values after the second period.


The effect of poisoning with Dithane M-45 on oxygen uptake and energy balance in adult rats. Adult white rats were kept on natural diet containing various doses of Dithane M-45 (Mn and Zn ethylene-bisdithiocarbamate). Oxygen uptake (VO2), metabolic rate and energy balance were determined at intervals of several days. Oxygen uptake and metabolic rate were not significantly changed in animals receiving Dithane M-45 in concentrations of 5 and 50 ppm but they were significantly decreased in the animals kept on the diet containing the preparation in concentrations of 500, 2000 and 5000 ppm. The authors conclude that changes in body weight of animals after poisoning with Dithane M-45 are due, both to reduced supply and requirements for energy.


Diurnal and seasonal variations of glycogen content in the rat brain. The effect of seasonal and diurnal variations on glycogen content in the brain was investigated in 3-month old Wistar rats. In the first experimental series, the glycogen content in the brain was determined every 2-months, throughout a whole year. In each experiment, the material was taken at the same time of a day. The results indicated that the brain glycogen content did not change significantly, during the periods of a year examined. In the second series of experiments, the glycogen content in the rat brain was assayed every 3 hours, during a 24-hour-period. A low content of glycogen in the rat brain was found during the night, with a pronounced decrease of this value between 9.00 p.m. and midnight. A possible relationship between the diurnal changes in the brain glycogen content and catecholamine metabolism in the central nervous system is discussed.


Studies of cerebral osmoreceptors in anesthetized dogs: the effect of intravenous and intracarotid infusion of hyper-osmolar sodium chloride solutions during sustained water diuresis. The function of the suggested hypothalamic osmoreceptors was investigated in dogs during light chloralose anesthesia. The dogs were subjected to an i.v. load of 40 ml/kg b.w.t. of a hypo-osmolar solution of sodium chloride and glucose. This degree of hydration was kept constantly by a specially constructed servo system based on the weight of the animal. During water diuresis the renal free water clearance remained essentially constant for several hours (mean about 0.2 ml/kg b.w.t. min). Renal sodium excretion was low (mean 0.82 mumol/kg b.w.t. min) and decreased continuously throughout the experimental period. I.v. infusion of hyperosmolar sodium chloride solution (1.33 mmol/kg b.w.t. in 30 min) was followed by prolonged parallel increases in free water clearance and sodium excretion, without any detectable change in the excretion of osmoles and potassium. The renal response to bilateral infusion of hyper-osmolar NaCl (1.33 mmol/kg b.w.t. in 30 min) into the common carotid arteries was identical to the response to i.v. infusion. The estimated increase in the osmolality of the carotid blood was 2.2%. In seven out of eight experiments intracarotid infusion of NaCl (1.33 mmol/kg b.w.t. in 8 min) did not elicit any reduction in free water clearance. On the contrary, an increase was found similar to that obtained after i.v. infusion. The estimated increase in the osmolality of the carotid blood was 8.4%. The present results question the validity of the currently held view that hypothalamic osmoreceptors play an important role in the control of the osmolality of plasma.


Normal values of blood morphotic elements, haematocrit and bone marrow cell pattern in adult Wistar rats. Since normal values of blood morphotic elements, haematocrit, and bone marrow cell pattern reported for adult Wistar rats by various authors differ investigations were carried out on a relatively large group of animals. The results were compared with the normal values obtained by other authors.


Effects on renal water and sodium excretion of infusions of either iso-osmolar saline or a hypo-osmolar solution of non-electrolytes. The effects of iso-osmolar and hypo-osmolar volume expansion on renal water and sodium excretion were studied in dogs during light chloralose anesthesia. Saline or a hypo-osmolar of glucose and urea was given i.v. (20 ml/kg b.w.t. in 60 min). From the start of this infusion the combined weight of the hydration infusate and the dog was maintained constant by a servo system, which controlled the rate of infusion of a hypo-osmolar solution. Consequently the degree of hydration increased linearly during the infusion period after which it remained constant throughout the experiment. No increase in free water clearance was seen after iso-osmolar volume expansion. The rate of excretion of sodium increased considerably. Hypo-osmolar volume expansion provoked a water diuresis during which the rate of excretion of sodium fell to less than 0.1 mumol/kg b.w.t. min. It is concluded that under the present circumstances infusion of iso-osmolar saline is not associated with a decrease in the rate of secretion of vasopressin.


Distribution and retention of indium113m in the organism of pregnant rats. The distribution and retention of intravenously administered indium (113mInCl3) were determined in pregnant female rats. The highest accumulation of indium was found in the placenta during the last period of pregnancy. Five hours after administration the retention of indium in the placenta was about 38% of the administered dose. In the fetuses of these females the amount of radioactive indium did not exceed 1% of the injected dose. In the last period of pregnancy the placenta is the critical organ for intravenously administered administered indium (InCl3).


Effects of lesions in the parabrachial nucleus on the mechanisms for central and reflex termination of inspiration in the cat. The effects of PCO2 and body temperature on the time course and peak amplitude of the central inspiratory activity (CIA) and the inspiratory "off-switch" threshold was studied in apneustic and non-apneustic cats. Apneusis resulted from lesions of the inspiratory inhibiting structures of the medial parabrachial nucleus (NPBM) and by interrupting vagal volume feedback. The cats were paralyzed and ventilated either proportionally to their phrenic output or at predetermined rate and volume. The dependence of the rate of rise and maximal amplitude of phrenic activity on PCO2 and body temperature were comparable in apneustic and non-lesioned animals. The Hering-Breuer volume threshold for inspiratory termination was increased following the rostral pontine lesions. Both hyperthermia and hypercapnia caused augmentation of the absolute rate of rise of inspiratory activity but hypercapnia, in contrast to hyperthermia, caused virtually no change in the fractional increment per unit time. With hypercapnia the inspiratory "off-switch" threshold was raised in the apneustic animals in intact ones, whereas hyperthermia did not seem to influence this threshold. In apneustic conditions expiratory duration remained constant, independent of the large variations in the inspiratory durations. Our results suggest that the NPBM merely provides an excitatory, threshold-lowering input to the inspiratory "off-switch" mechanism.


The effect of restriction of physical activity on adaptation to prolonged exercise in dogs. Eight-week restriction of physical activity markedly reduced the capacity for prolonged running. The rate of exercise-induced Tre increases was also significantly higher in comparison with control experiments. At the point of exhaustion blood glucose concentration and muscle glycogen content were similar in the control and cage-confined animals, however the rate of decrease in blood glucose level and muscle glycogen depletion during exercise were higher in the cage-confined dogs than in the controls.


Temperature effects on the inflation reflex during expiratory time in the cat. In order to obtain further information on the mechanisms controlling expiratory duration (TE) we have studied the effects of changes in body temperature on reflex characteristics of the TE-prolonging inflation reflex. In cats under light pentobarbitone anesthesia controlled volume changes were applied at various times in expiration and the changes in TE were measured from records of phrenic activity. Inflations falling in the last 20% of the control expiratory time were without effect. This reflex insensitive phase remained a constant fraction of expiratory time when respiratory rate was changed with temperature. The relative reflex responsiveness increased, and the volume threshold was reduced with increasing respiratory rate. The inflation reflex characteristics showed integration of the incoming pulmonary stretch receptor activity. The integrating mechanism exhibited a "leaky" character, the decay rate of which changed with body temperature. Functionally the duration of the inspiration-inhibiting activity controlling expiratory duration can be regarded as dependent on 3 main factors 1) the initial peak level of the inhibitory activity, 2) the amount and timing of the vagal afferent activity which adds to this inhibition, and 3) its rate of decay. The results suggest that all these factors are influenced by changes in temperature.


Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. II. Effects from segmental flexor reflex pathways. Interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as "Ia inhibitory interneurones") were recorded in the lumbar spinal cord of the cat. Volleys in ipsilateral and contralateral high threshold muscle afferents, cutaneous and high threshold joint afferents evoked a mixture of polysynaptic excitation and inhibition. These effects were ascribed to pathways activated by flexor reflex afferents (FRA) and in addition a specific ipsilateral low threshold cutaneous pathway. Ia inhibitory interneurones excited monosynaptically from flexor nerves received stronger net excitation by volleys in ipsilateral FRA than did extensor coupled interneurones, while the opposite pattern was seen from the contralateral FRA. These patterns are similar to those found in flexor and extensor motoneurones respectivey. The FRA inhibition in Ia inhibitory interneurones was partly mediated by "opposite" Ia inhibitory interneurones, i.e. those which are mediating the Ia inhibition of Ia inhibitory interneurones. The extent to which the FRA inhibition is transmitted by Ia inhibitory interneurones was roughly estimated by its susceptibility to recurrent depression by antidromic ventral root stimulation. The main conclusion is that most segmental pathways seem to evoke their effects in parallel to motoneurones and Ia inhibitory interneurones which are monosynaptically linked to the same muscle. The functional importance of this conclusion is discussed in a following report.


Transfer of I125-albumin from blood into brain and cerebrospinal fluid in newborn and juvenile rats. Human fetuses, rabbit fetuses and newborn rats have a relatively high concentration of protein in cerebrospinal fluid (csf) as compared with the adult. The present study was undertaken in an attempt to evaluate whether this high protein concentration in newborn rats is caused by a high permeability of the blood-brain-csf barrier to protein or by a low production rate of csf. The results suggest that the high concentration protein in csf in newborn rats is due to a low rate of production of csf rather than to an increased transfer of protein across the blood-brain-csf barrier.


Inhibition of reserpine, guanethidine and imiparmine of the uptake of 5-hydroxytryptamine by rat peritoneal mast cells in vitro. The effect of reserpine, guanethidine and imipramine of the uptake of tritiated 5-hydroxytryptamine by rat peritoneal mast cells was studied in vitro. The Km value for uptake of 5-hydroxytryptamine was 3 x 10(-7) M in this study. Kinetic analysis of the data obtained suggests that the drugs inhibits the uptake in a competitive manner, in the order of decreasing potency: reserpine, imipramine, guanethidine. For reserpine the Dixon plot resulted in two curves, each composed of 2 linear components suggesting inhibition of uptake of 5-hydroxytryptamine at 2 different levels or by 2 different mechanisms with different K1 values. It is suggested that the higher K1 value, representing an immediate effect of reserpine, stands for inhibition of uptake at the cell membrane. The lower K1 value possibly represents inhibition at the level of the membrane surrounding the intracellular storage organelles.


The vagal control of the ileo-cecal sphincter in the cat. In acute experiments on chloralosed cats the effect of efferent cervical vagal stimulation on a flow through the ileo-cecal sphincter (ICS) was studied. The motor activity of the jejunum, ileum and large intestine adjacent to the sphincter was recorded simultaneously. Vagal stimulation caused a decrease in the transphincteric flow and increased motor activity in the ileum. Increased motor activity in the proximal colon was recorded only occasionally. When the vagal nerves were stimulated during continuous splachine stimulation the transsphincteric flow was decreased although the tone and motility of the ileum was suppressed. Furthermore, guanethidine (1-3 mg/kg b.w.) blocked or suppressed the effect  of vagal stimulation on the transsphincteric flow while the excitatory response of the proximal colon was greatly enhanced. This indicates that the reduction of the transsphinctteric flow following vagal stimulation was at least partly due to a direct effect of the vagal nerves on the sphincteric muscle and not to a squeezing effect of that part of the colonic wall that surrounds the sphincter. Atropine (0.1 and 1 mg/kg b.w.) blocked all responses to vagal stimulation. Thus, both guanethidine and atropine blocked the vagally induced contraction of the ICS. Relaxation to the ICS  was never obtained by vagal stimulation even when the tone of the sphincter had been increased by infusion of noradrenaline.


A computer program for an open two compartment system distinguishing three models. A digital computer program is described for the estimation of parameters in an open two compartment system distinguishing 3 models. The mathematical function to be fitted to a given set of experimental data is given initial estimates for the parameters of the function. The program uses an iterative procedure to adjust the parameters until the sum of squares of residuals has converged to a minimum. Assuming that a given substance is introduced into compartment 1, the function can be fitted to the set of experiment data of that compartment. A set of experimental data from compartment 2 can also be included in the minimizing function. Two optional weighting functions are presented. From the constants of the two-exponential functions the physiological parameters of the three models are determined. Experimental observations of compartment 1 only allow for calculation of physiological parameters of two of the models.


The effect of local application of vinblastine or cholchinine on acetylcholine accumulation in rat sciatic nerve. The accumulation of acetylcholine (ACh) following nerve crush was inhibited by high concentration of colchicine (10(-1), 10(-2 M) and vinblastine (10(-2)-10(-4 M) in a dose-dependent manner. The two mitotic inhibitors were effective both when applied to axons (subepineural injections) and to perikaraya (injections into the lumbar intumescence). The results indicate that mitotic inhibitors, when applied locally to cholinergic motor neurons, may block the proximo-distal transport of ACh. The possibility is discussed that this blockade is caused by an interference with a microtubule mechanism in the axons. Evidence for an increased local synthesis of ACh near the site of injection into nerves also obtained with the highest concentrations of either substance used.


Release of vitamin B12-binding protein from isolated rat liver perfused with a synthetic medium. The unsaturated vitamin B12-binding capacity (UBBC) of the small molecular size vitamin B12-binding protein (SBP) release and albumin release into the medium and the fluid pressure in the portal vein were studied with respect to their ability to reflect the state of isolated perfused rat liver. The liver was perfused in vitro with a synthetic medium either with or without a gas carrier. Liver damage was induced by hypoxia or noradrenalin. Variations in experimental conditions resulted in different patterns of parameters reflecting different aspects of the liver state. The fluid pressure in the portal vein reflected sensitively the circulatory state but is not always a criterion of the general condition of the isolated liver. The albumin release is a criterion of functional state but did not always reflect liver damage. However, the amount of UBBC of SBP released into the medium is a parameter reflecting sensitively the functional capacity of the liver to produce protein and also seems to indicate liver damage. The use of this parameter provides supplementary information that cannot be obtained by either of the two more conventional parameters.


Gravitational stress and autonomic cardiac blockade. Arterial pressure, heart rate and cardiac output were recorded in eight healthy, male volunteers in the sitting position at normal gravity (1 G) and during a 4 min exposure in a human centrifuge to 3 G, the G vector in both conditions acting in the head-foot direction. The responses of the observed variables to the change from 1 G to 3 G were compared before and after combined beta-adrenergic and parasympathetic blockade of the heart induced by the i.v. administration of propranolol, 0.25 mg/kg bwt, and atropine, 0.03 mg/kg bwt. After blockade the heart-rate response to increased G averaged 22% of that observed without blockade. Mean arterial pressure at 3 G, and thus G tolerance, was significantly lowered after blockade, resulting in symptoms of retinal hypoxia ("greyout") towards the end of the 3 G runs in some of the subjects. G-induced reductions in cardiac output and stroke volume were significantly larger after blockade. Associated increases in total peripheral resistance were 56% before and 79% after blockade, the stronger vasoconstrictor response in the latter case thus being insufficient for maintenance of arterial pressure homeostasis.


Interaction between the hypothalamic defence reaction and cardiac ventricular receptor reflexes. The interference with regard to the cardiovascular and gastric motility responses which follows stimulation of the hypothalamic defence area (D.A.) and a simultaneous afferent input from cardiac ventricular receptors was analysed in chloralose-anesthetized cats. In spinalized animals with only the vagal efferent innervation of autonomic effectors from supraspinal structures intact, a D.A. stimulation increased the heart rate to the same level irrespective whether the cardiac receptor afferents were stimulated or not. This suggests that the vagal component of the reflex bradycardia of cardiac receptor origin was completely suppressed by the D.A. stimulation. The reflex gastric relaxation to cardiac receptor activation, mediated via vagal efferent non-adrenergic fibres, was similarly completely blocked by D.A. stimulation. In contrast, the reflex inhibition of the sympathetic outflow to the heart and vessels from cardiac receptors was still effective during a D.A. stimulation, a phenomenon which seems compatible with a simple summation of excitatory D.A. and inhibitory cardiac receptor influences on the sympathetic neurons. The modifying influence from ventricular receptors on D.A. responses closely resembles that exerted by the arterial baroreceptors. The two reflex mechanisms thus work in concert and synergistically with the hypothalamic influences to produce maximal cardiac output and skeletal muscle perfusion without undue increases of pressure load on the pump during a defence reaction.


The effects of neuraminidase and protamine chloride on potential clamp parameters of the node of Ranvier (Xenopus laevis). The effects of neuraminidase and protamine chloride on the ionic currents associated with step changes in membrane potential were studied. Neuraminidase (a hydrolase which cleaves glycosidically bound sialic acid) had negligible effects on the permeability properties. The polycation protamine chloride decreased the sodium as well as the potassium currents. The sodium equilibrium potential decreased during the experiments which indicates a gain in internal sodium concentration. The analysis showed that the effects on the currents were caused by a decrease of the specific permeability changes. No shift along the potential axis of the potential dependent parameters was observed.


Effects of gonadotrophins on the cumulus oophorus of isolated rat Graafian follicles. Graafian follicles were extirpated before the endogenous LH surge on the day prior to ovulation from PMS-injected immature rats. They were incubated in chemically defined medium in presence or absence of gonadotrophins for 4-10 h. After incubation the oocyte-cumulus complexes were recovered from the follicles and one group inspected by Nomarski interference contrast microscopy and one group was placed in saline containing hyaluronidase. In hormone-free medium both the oocyte and the cumulus cells remained morphologically unchanged: a dictyate oocyte surrounded by a compact mass of cumulus cells. Hyaluronidase did not detach cells from the cumulus structure. However, in presence of LH or FSH morphological changes developed in both cell types: the oocyte resumed meiosis as revealed by germinal vesicle breakdown and polar body formation; the cumulus structure became dispersed and embedded in a viscous matrix. The individual cumulus cells displayed pseudopodia-like processes of the cell surface. Treatment with hyaluronidase resulted in detachment of cells from the cumulus. The effects of LH described on the oocyte and cumulus cells were unimpaired in presence of cyanoketone or aminoglutethimide although these agents blocked the follicular relase of progesterone, estradiol and androstenedione as revealed by RIA. The results indicate that a close functional relationship exists between the two cell types of the cumulus oophorus, the oocyte and the cumulus granulosa cells. Both cell types are affected directly or indirectly by gonadotrophins and characteristical morphological changes develop synchronously in both cell types.


Glucose consumption in rat cerbral cortex in normoxia, hypoxia and hypercapnia. Glucose consumption was measured in the cerebral cortex of rats, anesthetized with 70% N20, under normoxic conditions, as well as in hypoxia (Pao2 about 25 mmHg) and hypercapnia (Paco2 80-85 mmHg). The method used was that Hawkins et al (1974), modified to allow studies of transients in glycolytic rate. Cortical glucose consumption in normoxia was 0.77 mumol-g(-1)-min(-1). It is concluded that whereas glucose consumption in the whole brain of unanesthetized rat may be close to 0.6 mumol-g(-1)-min(-1), that of the cerebral cortex is close to 0.8 mumol-g(-1)-min(-1). During the first 2 min of hypoxia, glucose consumption was increased to twice the normal, and during the fist 2 min of hypercapnia, the corresponding value was less thane third of the normal. After 15 min of hypoxia, the glucose consumption had returned towards control values. In "steady state" hypercapnia, the glycolytic flux was higher than in the inital phase although still below normocapnic values.


Blood flow changes in the submaxillary gland of the rat on parasympathetic and sympathetic nerve stimulation. Blood flow and secretion from the submaxillary gland of the rat was recorded. Stimulation of the chordalingual nerve evoked vasodilatation which was little, it at all, decreased after administration of atropine. The secretion evoked on parasympathetic nerve stimulation was greatly reduced but not totally abolished by parasympatholytic agents. Stimulation of the cervical sympathetic trunk evoked secretion, which was mediated both via alpha and beta-adrenoceptors and vasoconstriction which was abolished by dihydroergotamine, and thus seemed to be mediated via alpha-adrenergic receptors. After alpha-adrenoceptor blockade vasodilatation was seen on sympathetic nerve stimulation. This was abolished by the beta-adrenoceptor blocking agent propranolol.


The origin of impulses recorded from dentinal cavities in the tooth of the cat. Intradental nerve impulse activity can be recorded by means of electrodes inserted into dentinal cavities in the tooth of the cat. The following study has been conducted to investigate the origin ofthis impulse activity. The results suggest that the fibres from which the impulses are recorded must pass through the major part ofthe pulp between the recording electrodes. Furthermore, the results show that it is not possible to record discharges in the finest terminal branches in thepulpo-dentinal border zone using the present technique. However, the data obtained indicate that these terminal branches were activated during stimulation  resulting in recordable propagated axonal impulses.


Metabolic reactions to changes in core and skin temperature in man. The metabolic cold response, i.e. the increase in oxygen consumption above that for the given activity in a neutral environment, was measured in 7 subjects during cooling, resting or swimming in cold water (14, 16, 18, 20degrees C) and during rewarming in air (Ta 20, 30, 40degrees C), bicycling or resting. Esophageal temperatures varied between 38 and 34degrees C. Mean skin temperature was considered as equal to water temperature during cooling, and ranged between 25-35degrees C during rewarming in the different environments. Both central and peripheral cold stimulation induced metabolic cold responses. The skin temperature was the dominating factor in determining the response, especially in transient states. During rewarding a rising skin temperature suppressed the effects of even very low core temperatures.


Cardiac receptors in ducks--a link between vasoconstruction and bradycardia during diving. It has been demonstrated that cardiac receptors, most likely of the left ventricular type, are present also in the duck's heart. These receptors and their reflex responses (i.e. bradycardia and hypotension) could be blocked by intrapericardial administration of lidocaine. Initially, usch receptor blockade did not affect efferent vagal control of heart rate, as revealed by undiminished bradycardia in response to a standardized vagal stimulation. After cardiac receptor blockade, however, the duck's normal bradycardia response to head immersion was greatly reduced. The cardiovascular response to submersion was now instead characterized by a marked rise in arterial pressure, with superimposed bouts of intensified bradycardia and pressure reduction, evidently induced reflexly from the arterial baroreceptors. Meanwhile, the bradycardia response to standarized efferent vagal stimulation was still the same as before intrapericardial lidocaine injection. These results suggest that the marked rise in cardiac filling pressure following the intense shemo-receptor-induced constriction of both resistance and capacitance vessels, activates ventricular stretch receptors signalling in vagal afferents. Apparently, the activation of these receptors contributes crucially to the bradycardia and reduction of cardial output, which balance off the greatly increased peripheral resistance in the diving duck.


Protein synthesis with special reference to S-100 protein in brain slices from rats receiving a restricted protein supply. The synthesis of S-100 protein and that of soluble and total proteins was investigated using cerebral slices from rats fed a 20% or 3% protein containing diet for 6 days. Incorporation of radioactive amino acids into S-100 protein was significantly higher when rats were fed a diet containing 20% protein. No significant differences were obtained in the radioactivity incorporated into total or soluble proteins between the 2 dietary groups. 14C-leucine of aspecific radioactivity of 55 mCi/mmol or 3.2 mCi/mmol incorporated with time into total protein was similar for the 2 dietary groups. The time-dependent uptake of 14C-leucine by the slices and theinulin space remained unaffected by the dietary conditions used; and amino acid analyser estimates of the free amino acid pool showed no significant differences. Brain wet weight was 1.54+/-0.02 g and1.39+/-0.02 g for protein-fed and protein-restricted rats respectively. The corresponding body weight increased by 7.8 g/day or fell by 0.5 g/day. Although the differences observed in total protein synthesis were small the synthesis of a nervous tissue specific protein S-100 was markedly affected by short-term protein restriction.


Pathways for chloride and sodium transport across toad skin. The voltage dependecies of Na and Cl fluxes were investigated in the isolated toad skin. With Cl-Ringer's on both sides Cl outflux varied very little with clamping voltage. The same was true for the influx of Cl at depolarizing voltages (psii -psio lessthan0 mV), wheras hyperpolarization led to a marked increase in this flux. A net chloride influx under short circuit conditions indicated active transport of chloride. The outflux of Cl was a saturable function of outside Cl concentration. The outflux of urea was hardly affected by raising outside Cl concentration, and the effect of varying outside nitrate concentration on Cl outflux was likewise small. Both influx and outflux could be inhibited partially bt acetazolamide. The outflux of Na varied with the clamping voltage as would be expected for an ion transported by electrodiffusion, and it was shown that amiloride had no effect on Na outflux, so it was concluded that the Na outflux route is particular. In the absence of Cl in the outside solution a small outflux of Cl persists. Also this flux varied with the clamping voltage according to laws for electrodiffusion. The variation of the ratio of sodium outflux to chloride outflux with clamping voltage indicated free passive diffusion of both these ions under the conditions mentioned. A comparison of the outfluxes of Na and Cl in skins bathed with gluconate Ringer's outside showed that the outflux route of these two ions was cation selective (PNa/PCl=1.88). When the paracellular leak pathway of the skins was opened by exposing the outside to hyperosmolar urea solutions, the ratio of the transport numbers was found to be TNa/TCl=1.71. The roles of the two ions in determining the steady state current-voltage relationships were compared. At hyperpolarizing voltages most or all of the clamping current was carried by an inward Cl flux. By depolarization sodium influx plays an increasing role with increasing depolarization. Under short circuit conditions active chloride transport was found to contribute to the short circuit current.


Prostaglandin-mediated inhibition of noradrenaline release: its resistance to variations in rate of prostaglandine synthesis. Isolated rabbit hearts were perfused according to Langendorff. The bilateral sympathetic nerve supply to the organ was stimulated at intervals, and the overflow of noradrenaline and of prostaglandins of the E series in the effluent was assayed, using fluorimetric and bioassay methods, respectively. The synthesis of prostaglandins in the organ was stimulated, either by perfusing the heart at a low pO2, or by infusing nicotinic acid. Hypoxia increased the coronary flow, provided the prostaglandin synthesis was not inhibited, probably as a consequence of hypoxia stimulation was however, unaffected by hypoxia. Nicotinic acid also stimulated prostaglandin formation, doubling the overflow of the lipid in response to nerve stimulation. In this series, too, the release of NA induced by nerve stimulation was unaffected by stimulation of prostaglandin synthesis. It is concluded that local variations in the rate of prostaglandin synthesis are unable to change the degree to which the release of sympathetic neurotransmitter is inhibited. Furthermore, it is suggested that the prostaglandin synthesis in rabbit heart takes place in compartments, separated functionally or morphologically.


Prediction of propagation block on the basis of impulse shape in single unit recordings from human nerves. The occurrence of impulse block was studied in single unit recordings and related to impulse shape when peripheral nerves were impaled with tungsten needle electrodes. Exposed nerves were exploited in frog and cat and non-exposed nerves in man. Three different impulse shapes were seen: 1. Negative spikes of very short durations which nearly all propagated. 2. Positive double peaked spikes which all propagated. 3. Positive single peaked spikes which were of two different natures: one which propagated and one which did not. The findings suggest that urinary impulses recorded witha needle electrode impaling the myelin are positive and single peaked when the injury is minimal. Gradually a propagation delay might develop at the site of impalement giving rise to a double peak. Later the propagation may be blocked which is seen as a drop out of the second peak. The collected sample of observations indicates that it was possible to predict in practically all cases whether the propagation was blocked or not from the shapes of the single unit impulses and their alterations as seen by the tungsten needle electrode.


Effect of vasodilating drugs on external carotid and pulpal blood flow in dogs: "stealing" of dental perfusion pressure. Blood flow in the external cartoid artery (ECBF) and dental pulp (PBF) was measured during arterial infusion of vasodilators (isoprenaline, papaverine, acetylcholine and bradykinin). Systemic arterial pressure (AP) and local arterial pressure of the teeth (LAP) were recorded in a femoral and the lateral nasal artery respectively. All four vasodilators were found to increase ECBF and simultaneously reduce lateral nasal arterial pressure--or in other words-to STEAL" PERFUSION PRESSURE FROM THE TEETH. AP remained practically unchanged whereas PBF was variably affected. During infusion of isoprenaline PBF decreased on average by 19% of control. Papaverine nearly doubled PBG, while bradykinin caused no consistent change. Great pulpal flow variations were often recorded during constant acetylcholine infusion rate. The variable effect of the four vasodilators on PBF could partly be explained by the fall in LAP. Calculated pulpal resistance (LAP/PBF) showed no consistent change during isoprenaline infusion, bradykinin caused a slight fall and papaverine reduced LAP/PBF by 49%. The experiments demonstrate that due to the "stealing" of dental perfusion pressure caused by vasodilation in the neighbouring tissues, the effect of vasodilators on pulpal resistance vessels cannot be estimated without knowledge of the pressure in the small arteries directly feeding the teeth.


Aging of schizophrenic patients as seen through the Rorschach test. The authors have repeated, on the average 29.7 years later, Rorschach test in 11 schizophrenic men and 19 schizophrenic women. This work was carried out in the course of a follow-up study of schizophrenics more than 65 years of age. Analysis of the records showed that the only differences between the first and second examinations were increases in animal and popular responses in old age. The authors have tried to relate these findings to the general trends of schizophrenic development in senescence.


Effect of brain injury on social adaptability. Longitudinal study on frequency of criminality. The study tried to clarify social adaptability of persons with brain injuries by using a long-term criminal development as a criterion. Randomly chosen 507 subjects whose open injury originated from the Second World War were followed up for about 30 years. The criminal acts commited by 29 (5.7%) of these subjects were so severe that they led to imprisonment. Criminality was not found in the subjects with fronto-temporal injuries more often than in those with injuries to the other areas. Subjects with injuries to the dominant hemisphere appeared to have more criminality than subjects with injuries to the non-dominant hemisphere. The criminal acts were often very accidental and had happened only after several decades following the head injury.


Phylogenetic adaptations and the genetics of psychosis. There is evidence that many social skills and responses which are of adaptive value are under a significant degree of genetic control. It is suggested that in states of hyper-arousal these skills are displayed in inappropriate and incomplete forms and that such behaviour constitutes psychosis. Genetic variation in these skills, under polygenic control, appears to be a determinant of the adaptiveness of the personality, with individuals at the extremes of the distribution tending to be maladjusted, chronically overaroused, and vulnerable to psychotic breakdown. Since the individual subjects's psychotic symptomatology will relflect the make-up of his genotype, the hypothesis is consistent with observed familial occurence of the different froms of functional psychosis. The hypothesis explains many of the characteristic manifestations of psychosis, including those in symptomatic psychosis, and also the genetic association with personality disorder. Evidence for the hypothesis and some predictions it generates are briefly reviewed.


A hospital population of schizophrenic patients undergoing change. From a census investigation in 1953 at the Aarhus Psychiatric Hospital, 393 schizophrenic patients were selected (Population 53, P53) and compared with 282 schizophrenics from the 1962 census at the hospital (Population 62, P62). Through hospital records and the central psychiatric register in Denmark, the population from 1953 was followed for 18 years, the 1962 population for 9 years. At admission it appeared that few of the patients had ever married. This was patriculary so for the males. The males were also found to belong to a lower social group than would have been the case in a sample from the general Danish population. In 1962 more patients had obtained State Disability Pension before admission than the 1953 population. More than two-thirds of all admitted schizophrenic patients were in psychiatric hospital within 3 months after onset of illness. Around two-thirds were admitted upon the request of relatives. In the investigated period the expenses for medicine per patient had increased eightfold, whereas expenses for food had less than doubled. Only 15% of the schizophrenic patients in the investigated populations were discharged to their homes. Four per cent were discharged to a nursing home; 22% had died. Of the 15% discharged to their homes, about 50% were readmitted for some time at a later period. In 1962, however, many more patients were discharged after less than 2 years of hospital stay than was the case for the 1953 population. The readmission rates increased from 38% in the 1953 population to 62% in the 1962 population.


Long-term follow-up of schizophrenic patients in Edinburgh. This study is a 12-year follow-up of 153 subjects diagnosed as suffering from schizophrenia or paranoid psychoses. They had their key discharge in the years 1959-61 and were first followed-up at 12 months after discharge (Renton et al. ((1963)). Important findings were that outcome was related to mental state on discharge and also to the factor of continued neuroleptic medication. At this second follow-up 12 years later the important issues that have emerged are the differences in outcome between men and women and the apparently high death rate for men. The outcome in term of work, re-admission to hospital and death was much worse for male subjects.


A reliable clinical technique for investigation of the experienced reality and unreality qualities connected with everyday life experiences in psychotic and non-psychotic persons. Eight different pairs of positive and negative qualities of experienced reality are defined. It is described in detail how these qualities can be recorded in relation to specified varieties of experience: a)sensory perceptions, b)fantasies, and c)"thinking of actually existing objects or properties in persons." In a study of 15 non-psychotic patients it was found with a very high reliability that the three varieties of experience each had their characteristic constellation of positive and negative values of the eight qualities of reality. It is pointed out that knowledge of such normal constellations is a logical prerequisite for being able to classify other varieties of experience (hallucinations, delusions, and others) as being pathological.


The token economy in the National Health Service: possibilities and limitations. The effects after 1 year of the introduction of a token economy system into a long-term male psychiatric ward of 45 mainly schizophrenic patients are described. The main objectives were (1) to define the limits of such programmes in "average" National Health Service conditions, where additional resources in staff, finance, and facilities are very limited and (2) to introduce the principles and techniques of behaviour modification to nursing staff. The programme succeeded in reducing social withdrawal and apathy and in increasing self-care skills and involvement in constructive activity. There was no change in the level of socially embarrassing behaviour. The major limitation affecting the maintenance of the programme was found to be the rapid turnover and unpredictable changes in nursing staff. It was concluded that such programmes are feasible with very little in the way of increased resources, and that such efforts will continue to be necessary in view of the existing large numbers of long-tern patients and the slow but significant accumulation of new patients.


Dimensions of adolescent in-patient behaviour. 140 adolescent in-patients were rated on a 40-item, 3-point behaviour scale. A principal component analysis was made and two major factors emerged which accounted for 44.3% of the total variance: one factor related to level of functioning and overinhibition and the other to aggression. A graphical representation of the patients with respect to the above factors provided important information as regards prognosis and clinical diagnosis. As in previous related studies (Klein & Davis (1969)), the validity of clinical diagnostic categories was confirmed and information on the process of making these diagnoses was provided.


Frequency of mental disorders in old age. Examples of comparability of epidemiological investigations in relation to utility in planning. Due to the increase in the number of old people, diseases of old age have acquired more and more importance. In estimating the need for psychiatric hospitals and nursing homes, epidemiological investigations are necessary. Only relatively few population investigations of the old-age population have been carried out, and most of these have been carried out in countries in Northern Europe, which are closely related culturally and socially. In the present paper nine investigations are described in relation to certain central factors which include the purpose of the investigation, description of the population, selection of probands, and statistical concepts used, the collection of data, and the main results. Seven of the investigations give results in the form of prevalence, two investigations calculate incidence and morbidity risk. It is concluded that comparison of the various results is difficult as most of the authors have not intended their investigations for mutual comparison. It is clear that there are many dissimilarities in the milieus involved, in the methods used, in the prerequisites of the interviewers and assessors, and in the classification of the results. The investigations presented have been used for evaluation of prognosis and planning of care for the old-age population. It must be said that an investigation is an expression of local truth and as such often usable in local planning, but on the other hand it is not often possible to utilize results from investigations carried out in outside regions for more than a rough basis for local prognosis and local planning. It must therefore be stressed that in future investigations more standardized methods and better correlated descriptions are necessary.


The duration of maintenance therapy in chronic schizophrenia. The incidence of relapse was compared between two groups of chronic schizophrenic patients (mean duration periods 19 months and 29.5 months) discontinuing depot neuroleptic injections, and matched controls remaining on depot injections. The results show a higher relapse rate in patients discontinuing injections, significant at the 1% level, in both groups. The proportion of patients improving upon resumption of depot injections confirms the importance of this form of medication in comparison to prescribed oral medication. The results strongly suggest that there is a significant therapeutic gain in continuing maintenance therapy with depot neuroleptic injections for a minimum period of 3 years after the last relapse in a substantial proportion of chronic schizophrenic patients.


Exploratory behavior in patients suffering from senile dementia: a comparison with children. Thirty-seven patients with the diagnosis of senile dementia and 70 children aged 6 months to 4 years were observed in three tasks that stimulated exploratory behavior. The subjects were rated according to the frequencies of certain forms of behavior in 52 variables. It was assumed that certain behavior would be more frequent among children in specific age periods and for that reason a factor analysis of the children's behavior would generate factors characterizing clusters of behavior typical for certain periods. The factor analyses of the children's behavior yielded three factors, which were interpreted as an oral factor, a factor characterizing interest in three-dimensional relationships, and a factor regarding goal-directed manipulation. Indices of the three factors demonstrated that the oral factor had a very high frequency in the infants 6-11 months old; after that age it decreased steeply and disappeared at about 2 years of age. Activities involving three-dimensional relationships and goal-directed manipulation were scarcely displayed in the youngest infants but appeared at about 12 months. Both modes of exploratory behavior tended to disappear before the age of 4. Analyses were carried out to see if the behavior of the patients yielded similar factors, and to see if the distributions of the factor indices for the group of patients, when broken down according to the degree of mental deterioration, had forms similar to the distributions for the children in the different age groups. Similar factors were obtained for the patients, but the structures were less clear and less meaningful than those obtained for the children. The forms of the distributions of factor indices over the degree of mental deterioration were similar to the distributions over the age groups for the children. Motor activity was reduced among more deteriorated patients. When explaining the childlike strategies in the exploratory behavior of the demented patients, it was hypothesized that, due to deficient memory, the patients had to manipulate the objects to find their qualities. This exploratory behavior was more or less advanced and flexible depending on the degree of mental deterioration. However, possible negative effects of high anxiety and high social inhibition were also touched upon.


Objective symmetry detector method for gammaencephalography. V. Variation in the subjective analysis of brain scintigrams. The variation caused by the subjective interpretation of brain scintigrams was evaluated and found considerable. It was concluded that the objective analysis of results offered by the objective symmetry detector method for gammaencephalography is advantageous, especially in the screening of large patient materials with a low incidence of brain lesion cases.


Adverse effects of lumbar myelography with amipaque and dimer-X. The adverse effects in a series of 50 lumbar myelographies with Amipaque were compared with those in a corresponding series, examined with Dimer-X. Side effects occurred in 58% of the cases examined with Amipaque and in 68% of the Dimer-X series. No seizures occurred in 58% of the cases examined with Amipaque and in 68% of the Dimer-X series. No seizures occurred in either series but slight fibrillations of fasciculations appeared in 2 Dimer-X patients. Hyperreflexia of the legs was recorded in 22% of the Amipaque and in 36% of the Dimer-X cases. Other adverse reactions to the media were mild to moderate. Some burst activity, but no definite paroxysmal abnormality was noted in EEG recordings in 2 Amipaque cases. The low epileptogenicity of Amipaque has ensured a wider safety margin of lumbar myelography.


Persistent hypoglossal artery, diagnostic criteria. Report of a case. After a brief racapitulation of the embryology of the vertebrobasilar arterial system, one new case (the 26th) with a persistent hypoglossal artery is presented. As in this case a well developed posterior communicating artery existed, new diagnostic criteria have been formulated.


Spinal cord vascularity. II. Extraspinal sources of spinal cord arteries in the rat. The arrangement of extravertebral sources of spinal cord arteries in the rat is similar to that in man. Some differences, however, do exist, concerning mainly the arrangement of spinal branches supplied by the subclavian-vertebral arteries. Contrary to the situation in man, the vertebral artery in the rat appears to be the sole source of blood supply to the cervical cord. A high incidence of variations or anomalies of the vertebral artery in the rat existed. Vascular variations in the upper left thoracic spaces were frequent in the rat and more complicated than in man. In both species, a poor supply of significant spinal cord feeders from the superior intercostal artery of the costocervical trunk was found. Variations in the origin and branching of the aortic segmental arteries occur in both species. In man the major variation consists of two or more intercostal arteries arising from a common stem, while the rat more often displays a rudimentary subcostal artery. Finally, the ileolumbar arteries in the rat are constant branches of the lumbar aorta. Despite these differences in the vascular anatomy, the rat seems to be well suited for experimental comparative investigations, not feasible in man.


Spontaneous carotid-cavernous fistulas: phlebographic appearance and relation to thrombosis. Six consecutive cases with spontaneous carotid-cavernous fistulas were examined with orbital phlebography and bilateral carotid angiography. One of the fistulas was fed only by one internal carotid artery, 1 only by the accessory meningeal branch of the maxillary artery, while 4 were supplied by external as well as internal carotid arteries. The findings at phlebography seem to be characteristic. Thrombosis was demonstrated in all 6 cases. Different mechanisms for the genesis of thrombosis in association with carotid-cavernous fistulas are proposed. Alternative therapy methods are discussed.


Radiology for detecting brain tumor recurrences. Angiography, 99Tcm-pertechnetate scintigraphy and encephalography are compared in their efficacy in the detection of tumor recurrences in 45 patients following brain tumor resection. No single method is always preferable and the best way of detecting a particular tumor recurrence is based on the location and nature of the primary tumor. Scintigraphy is the method of choice for performing routine postoperative follow-up. In cerebral hemisphere tumors angiography may be replaced by brain scanning which is a lesser procedure for the patient and does not necessitate hospitalisation. Encephalography is the examination favoured for detecting recurrences near the base of the skull. Angiography is the best method for demonstrating recurrences near the surface in the region of craniotomy and is essential before reoperation.


Vascular complications following needle puncture of the liver. Clinical angiography. Angiography after liver puncture was performed at different intervals in 51 patients. Fourteen cases had abnormalities believed to be caused by the puncture. Most of these were small but there were also 4 cases with large liver hematomas and 1 case with an abscess between the liver and the abdominal wall, none requiring acute surgery. No certain correlation between the severity of the injury and the diameter of the puncture instrument could be assessed.


Radiographic measurements of the radio-carpal joint in normal adults. Radiography of 60 normal wrists was performed in 50 adults to determine the inclination of the distal joint surface of the radius. The central ray was directed 10 degrees proximally in postero-anterior projection and 15 degree proximally in lateral projection. The values obtained were compared with those from perpendicular projections. No dfferences were found between the two p.a. projections. In the lateral projection with the central ray directed proximally the measuring points were better defined, resulting in significantly increased exactness of the measurement. The mean value for the volar inclination was 9 degrees in the latter projection.


Prognostic factors in mammary carcinoma. The simultaneous prognostic influence of multiple clinical and microscopic features of mammary carcinoma was analysed in 581 women with radical mastectomy. The most important of these features were connected with the extent of the disease in the axillary lymph nodes. In substantial groups of patients, however, a favourable outcome could be predicted from microscopic features of the primary tumour, viz. tubule formation, mitotic frequency and elastosis.


Results of irradiation of tumors in the region of the pineal body. The clinical findings and results of radiation treatment in 14 patients with tumors in the region of the pineal body are presented. The neurologic signs and symptoms improved significantly in 11 patients (79 per cent). The survival rate for five years or more was 50 per cent. Radiation therapy as the primary method of treatment is discussed.


DNA-synthesis of lymphocytes in hyperthyroid and euthyroid subjects. Effect of 131I therapy on hyperthyroidism. The DNA-synthesis of human lymphoid cells as estimated by the measurement of thymidine incorporation in vitro was investigated in healthy controls and in patients with various thyroid disorders before and after therapy. Hyperthyroid patients treated with 131I and surgery (euthyroid at initial blood sampling before surgery), patients with atoxic nodular goitre treated by surgery and healthy untreated control individuals comprised the material. The synthesis of DNA in lymphocytes was higher in hyperthyroid patients in comparison with euthyroid individuals, and decreased subsequent to 131I therapy in the hyperthyroid patients. No decrease was recorded in the other groups of patients. No evidence suggesting a change in the lymphocyte reactivity to thyroglobulin was found in any of the patient groups.


A preliminary experiment on regression of human ovarian tumor transplants in athymic nude mice following a single exposure to 60Co radiation. Human ovarian tumour transplants (AN-LE) are grown in the thymus defective nude mouse mutant (nu/nu BALB/c/A/Bom). Procedures for local irradiation of the tumors with 60Co-radiation are described. An introductory test of the usefulness of these transplants in studies of radiation effects on human tumors is performed by investigation of the time course of regression of AN-LE transplants in 6 mice, following single exposures to 375, 750 1 180, and 1 575 rad, respectively.


Influence of diagnostic roentgen doses on human chromosomes and influence of age on the aberration yield. Urography was performed in 2 groups of patients (one comprising patients aged 7-18 years, the other patients aged 8-32 months) under constant conditions. The skin dose ranged between 1 and 4 R. Blood samples were taken before, immediately after and 24 hours after the irradiation. A significantly increased number of aberrant cells was found only in the blood samples taken 24 hours after irradiation. No age-dependent influence on the radiation sensitivity in vivo was found.


Liver biopsies in epileptics during anticonvulsant therapy. Liver function tests, performed in 11 epileptics under antiepileptic treatment for 10-35 years, showed a slight increase in serum alanine amino-transferase in six patients and a marked increased level of serum alkaline phosphatases in four. Liver biopsies revealed few uni- or paucicellular necroses in five patients. Granulomatous hepatitis was found in one patient in whom sarcoidosis was later diagnosed. None of the biopsies showed signs of permanent liver damage.


Anticonvulsant osteomalacia determined by quantitative analysis of bone changes. Population study and possible risk factors. Material has been obtained by biopsy from the right iliac crest of 60 adult epileptic out-patients receiving chronic anticonvulsant therapy with diphenylhydantoin (DPH), either in single-drug or combined-drug regime, and of 16 controls with the same distribution by sex and age. Four (7%) of the epileptics were hypocalcemic and 25 (42%) had elevated serum alkaline phosphatase values. A quantitative analysis of the morphological bone changes was performed on decalcified and undecalcified bone, using integrating filters and the point count principle. An increased amount of unmineralized bone was found in 32 (53%) of the epileptics. The trabecular osteoclastic resorption surfaces and the mean volume of periosteocytic lacunae were increased in 36 (69%) and 45 (75%) patients, respectively. The calcification rate was decreased in relation to what is referred to elsewhere as normal. The bone changes suggest a mineralization defect analogous to osetomalacia with secondary hyperparathyroidism. An increased osteoid volume or thickness and decreased calcification rate were correlated to low dietary vitamin D intake, low exposure to sunlight, high hepatic clearance rate of DPH, combined-drug treatment and the male sex. These parameters should be considered risk factors of anticonvulsant osteomalacia.


Serum lipids in alcoholics.

Serum lipids in alcoholics. Fasting serum lipid values (cholesterol, triglycerides and phospholipids) have been analysed in a group of 85 male and 10 female alcoholics of various ages in connection with an acute drinking bout and compared to the values of twice as many control subjects. The most prominent finding was an increase in the mean concentration of triglycerides and phospholipids, most marked in the younger age groups. The elevations, however, were moderate and most alcoholics had the same serum lipid values as the controls. Serum triglyceride values above 2 and 3 mmol/1, respectively, occurred in 23% and 4% in controls and in 28% and 13% in alcoholics. It is suggested that excessive intake of alcohol induces hypertriglyceridaemia only when other factors are present. One such factor may be a reduced i.v. fat tolerance.


Ventricular fibrillation after intravenous atropine for treatment of sinus bradycardia. A patient with acute myocardial infarction and sinus bradycardia has been treated with 0.5 mg atropine intravenously. Shortly after the injection he showed a sinus tachycardia, then developed ventricular ectopic beats, ventricular tachycardia and ventricular fibrillation, which was treated successfully with electrical countershock.