Reproducibility of the intravenous galactose tolerance test. The reproducibility of the intravenous galactose tolerance test was investigated in eight healthy volunteers by performing the test five times under identical conditions in each individual. The results show that the interindividual scattering is much greater than the intraindividual variation. Therefore, and in connexion with the results of a previous investigation, the conclusion can be drawn that the intravenous galactose tolerance test is more suitable for the longitudinal course of patients than for the detection of an impaired liver function. A simplification of the test is possible by measuring the fasting galactose concentration and the blood galactose concentration 40 minutes after the galactose load.


On the applicability of statements on drinking and dietary habits for the calculation of risks or organ damage in chronic alcoholics. Data from 12 alcoholics admitted to a detoxication ward on two separate occasions revealed great differences in statements on drinking and dietary habits between the two interrogations. The findings clearly demonstrate that such statements do not give reliable informations on drinking and dietary habits during prolonged periods. Furthermore, data from 61 patients show that a classification into chronic and intermitent drinkers only to some extent improves the possibilities to calculate the alcohol consumption over prolonged periods, since because of e.g. frequent or prolonged hospitalizations many chronic drinkers may be intoxicated during fewer days of the year than intermittent drinkers.


Elimination of paracetamol in chronic liver disease. Serum concentrations of paracetamol were followed after oral administration of the drug to 21 patients with liver cirrhosis, 4 patients with secondary liver cancer, and 15 hospitalized patients without clinical evidence of liver disease. The cirrhotic patients had 50 per cent longer half-lives of the drug. They also had significantly higher values of AUC during the first 360 minutes, in spite of almost identical means values of Cmax and tCmax. Significant differences in paracetamol elimination between cirrhotics with and without ascites, or between cirrhotic with and without porto-caval shunt could not be demonstrated.


Endopeptidase activity of the brush border of human enterocyte. Succinyl-trialanine-p-nitroanilide (Suc-Ala3-pNA) has been described earlier as a convenient substrate for pancreatic elastase which is not split by trypsin and chymotrypsin. An enzyme activity splitting Suc-Ala3-pNA has been found in the supernatant of the mucous membrane of human small intestine homogenized with Triton X-100.


The role of prostaglandines in peristalsis of the human colon. Prostaglandines (PG) of the E and F series cause peristaltic activity in isolated longitudinal muscle strips of the human colon. As this phasic motor reaction can be varied by acetyl choline and adrenaline it was supposed, that prostaglandines contribute to peristalsis. The role of PG E and F in the human colon was studied by inhibiting the prostaglandine synthesis and by antagonizing the prostaglandine-effects. Indomethacin proved to be a suitable inhibitor. HR 546 was found a powerful antagonist. The effect of Pentagastrin and Cholecystokinin (CCK) on peristaltic activity were suppressed by Indomethacin and HR 546. The inhibition of peristalsis by Indomethacin and HR 546 was removed by high doses of PG E and F. On the basis of these results the role of PG for the motility of the gut is discussed.


The pressure profile of the common bile duct an experimental study in 15 mongrel dogs. In clinical urology the urethral pressure profilometry, developed by Brown and Wickham in 1969, is a well known diagnostical method. To our knowledge this type of investigation was not made in the common bile duct. In order to evaluate this method as an eventual clinical preoperative endoscopic method, especially in disorders of the choledocho-duodenal junction, choledochal pressure profile studies were made in 15 anesthesized mongrel dogs via a duodenotomy. The method was made according to the internationally advised standards of the urethral pressure profilometry. The mean contact basal pressure level in the choledochal duct amounted to 10,9 +/- 2,17 (sem) mm Hg. A statistically significant biphasis pressure elevation was seen in the region of the choledocho-duodenal junction (p less than or equal to 0,05). The mean pressures of the proximal and distal pressure elevation amounted to 59,8 +/- 8,51 (sem) mm Hg and to 54,3 +/- 7,13 (sem) mm Hg. The proximal top was located at 3,68 +/- 0,28 (sem) cm and the distal top at 0,96 +/- 0,07 (sem) cm distance from the orifice of the papilla. The total length of the elevated pressure zone amounted to 5,50 +/- 0,29 (sem) cm and the length of the elevated pressure zone of the distal top was 1,58 +/- 0,10 (sem) cm. These data correlate with the morphological structure of the choledocho-duodenal junction as mentioned in literature and illustrated with X-ray investigation and casts of the distal choledochal lumen. Our data show that with choledochal pressure profilometry pressure and length of the sphincter of Oddi can easily and safely be determined. In combination with endoscopy the technique can be of value in preoperative and postoperative evaluation of the function of the choledocho-duodenal junction.


Functional and morphological abnormalities of the small intestinal mucosa in pernicious anemia--a prospective study. Small intestinal mucosal function and structure was investigated in 13 patients with pernicious anemia prior to and after treatment with vitamin B12. Histological abnormalities of the jejunal mucosa were shortening of villi of varying degree, increased infiltrate of the lamina propria with monocytes and plasma cells and megalocytosis of the absorptive epithelial cell. Malabsorption of d-xylose occurred in 45%, fat in 30%, vitamin B12-IF complex in 69%, hypocarotinemia in 23% and hypoalbuminemia in 30% of the patients. By contrast, digestive brush border enzymes, i.e. disaccharidases, alkaline phosphatase and leucyl-naphthylamidase were not altered in pernicious anemia. Patients with significant jejunal mucosal abnormalities and decrease of the absorptive surface demonstrated malabsorption of one or more nutrients. Morphological and functional abnormalities were restored to normal after treatment with vitamin B12, suggesting that small intestinal changes in pernicious anemia constitute primary systemic manifestations.


Focal nodular hyperplasia of the liver and contraceptive steroids. A case of Focal Nodular Hyperplasia of the liver in a young woman taking oral contraceptives is described. The parenteral administration of an elevated dosage of progesterone in a concentrated period of time is a remarkable feature of this case. The vascular alterations, which consisted of a marked increase of arterial and venous formations, intimal proliferation, diffused thrombosis, and the presence of large blood spaces recalling "peliosis hepatis" are the most salient microscopic findings. We should not exclude the possibility that these peculiar vascular alterations be the real effect of steroid hormones on a pre-existent hepatic lesion.


Defective neutrophil chemotaxis corrected by levamisole in Crohn's disease. In a 26-year-old man with Crohn's disease, evaluation of the neutrophil polymorphonuclear (PMN) function showed marked impairment of chemotaxis, while NBT tests, phagocytosis, random migration and adhesiveness were all normal. PMN chemotaxis was found normal after levamisole therapy.


Maternal, foetal and neonatal blood creatine-phosphokinase-activities and creatine-phosphokinase-isoenzymes after labour with and without epidural analgesia and after caesarean section. Maternal, cord and neonatal blood creatine-phosphokinase (CK) activities and CK-isoenzymes were determined in connection with 24 labours after normal pregnancies. In eight cases there was a normal vaginal delivery; in another eight cases there was a normal vaginal delivery with segmental epidural analgesia; and in the remaining eight cases there was an elective caesarean section under general anaesthesia. The lowest maternal blood CK-activities were seen in connection with caesarean section. There was a statistically significant difference in the maternal CK levels after delivery between cases with caesarean section and normal labour (P less than 0.05) and between cases with caesarean section and labour with segmental epidural analgesia (P less than 0.001). Most of the maternal CK-activity was of muscular type, and there were no statistically significant differences in isoenzyme fractions between the different groups. The neonatal blood CK-activities were at their peak at the age of 1 day in all groups. Between the groups there were no statistically significant differences in cord or neonatal blood CK-activities at any time. Most of the cord and neonatal blood CK-activity was also of muscular type, and there were no significant differences in the CK-isoenzyme fractions between the groups.


Serum cholinesterase variants in the Danish population. A total of 1278 adult patients were screened for serum cholinesterase (E.C. 3.1.1.8) variants. The following were used for phenotyping of variants: dibucaine, fluoride, chloride, and urea. The observed incidence of cholinesterase variants in the Danish population was similar to that found in other European countries.


Hepatic release of fluoride from halothane under hypoxic and non-hypoxic conditions in the dog. Six dogs were subjected to halothane anaesthesia under hypoxic and non-hypoxic conditions. Plasma fluoride levels in hepatic venous and arterial blood, as well as blood flow to the liver, were measured during anaesthesia. The amount of fluoride released by the liver could thus be calculated. Release of fluoride took place in all animals during non-hypoxic halothane anaesthesia. The amount released varied between the individual animals and in three of them it rose further during hypoxic anaesthesia. The occurrence of defluorination of halothane, even under nonhypoxic conditions, may indicate a reductive metabolism in at least some parts of the liver. The significance of this hypothesis is discussed.


In vivo lung uptake of lidocaine in pigs. A mixture of 14C-labelled lidocaine and indocyanine green dye (IG) (Cardiogreen) was injected as a bolus into the pulmonary artery in pigs (15-25 kg). Time-concentration curves for both substances were constructed from 20s blood samples taken from the common carotid artery for approximately 20s. The extraction of lidocaine in each sample and the 95% first passage uptake (FPU) were calculated, assuming that IG is inert with respect to the lung and that it remains within the vascular compartment. The IG curves were also used to calculate cardiac output. The acid-base status and arterial blood pressure or ECG were also followed. Each animal was given two injections. When 0.5 mg/kg b.w. lidocaine was injected, FPU was 41 +/- 3%; at a dose of 2 mg/kg b.w., FPU was 28 +/- 3% (P less than 0.05). The initial extraction during the first 2 s after appearance of the substances was approximately 80%. This level declined with subsequent samples, and the decline was equally rapid at both dose levels.


The influence of thoracic epidural analgesia on the circulation at rest and during physical exercise in man. The effects of thoracic epidural analgesia (TEA) on the circulation at rest, during, and after physical exercise were investigated in 10 volunteers. At rest, TEA did not affect oxygen consumption (VO2) or cardiac output (Q), but heart rate (HR) was,  increased by 7 beats/min, and stroke volume decreased correspondingly by 13 ml. Systolic arterial blood pressure was slightly reduced, but no other changes in systemic or pulmonary circulatory parameters were produced. TEA did not change VO2 during exercise, a 2.11/min reduction of Q being accompanied by a 4.2% increase of oxygen utilization coefficient. HR showed a relative reduction of about 10%. At moderate work loads during TEA, systemic arterial blood pressures were significantly lower than during control exercise. The resulting rate pressure product (RPP) was markedly reduced, while total peripheral resistance (TPR) remained unchanged. During recovery after the termination of exercise during TEA, VO2, Q, HR, RPP and TPR fell more rapidly towards values obtained at rest. From a clinical point of view the results support the safeness of TEA and also support its use in surgical patients with heart disease.


Sympathetic nervous system response to lidocaine induced seizures in cats. The effect on arterial pressure, EEG, preganglionic sympathetic nervous activity and pulse rate of repeated intravenous administrations of lidocaine (3 mg/kg) was investigated in cats anaesthetized with nitrous oxide. A continuous high voltage, burst-suppression EEG indicating constant seizure activity was found, whereas arterial pressure and sympathetic nervous activity did not change significantly. Although the onset of EEG seizure activity did not change the mean sympathetic activity level, the pattern of firing changed dramatically as every EEG seizure triggered a burst of sympathetic impulses. Barostatic reflexes were active after lidocaine administration unless seizure activity occurred. Thiopental 5 mg/kg given intravenously to cats during continuous lidocaine-induced EEG seizures always abolished the seizure activity without excessive depression of arterial pressure.


Adsorption of insulin by infusion materials. Doubt about insulin adsorption has been an obstacle to rational insulin treatment by i.v. infusion. The influence of several factors on adsorption was therefore studied using a radioimmunoassay technique to determine insulin levels. When 8 to 128 IU of insulin were added to 500- and 1,000-ml containers, a linear relationship was found between the amount added and the amount delivered to the patient, permitting the design of a practical nomogram. In other experiments, 32 IU of insulin was added to 1,000 ml containers. The type of insulin did not influence adsorption. Half of the 32 IU added to soda-glass and siliconized bottles were adsorbed, while plastic containers adsorbed less. Neither the type of infusion solution (except for 60% glucose), nor the type of infusion set infuenced adsorption. Human serum albumin prevented adsorption only incompletely.


Epithelial mucins of the gastro-intestinal tract of Egernia cunninghami. Epithelial mucins of the gastro-intestinal tract of Egerina cunninghami, an Australian lizard, were investigated by several histochemical stains. The results obtained showed that the gastro-intestinal tract of this reptile has several types of mucus-secreting cells. Mucins secreted by the oesophagus, intestines and cloaca were predominantly acid-sulphated mucins, while the mucus neck cells of the gastric glands produced neutral mucins and the epithelial cells lining the gastric surface secreted a mixture of both neutral and acid mucins.


The exocrine pancreas in triamcinolone-treated mice. A light and electron microscopy study. 6-week-old ICR strain female mice were given between 16 and 21 daily injections of the synthetic glucocorticoid, triamcinolone diacetate (8 mg/kg body weight). Portions of their pancreas were examined by light and electron microscopy and compared with untreated littermate controls. Despite marked variability from animal to animal and lobule to lobule, triamcinolone treatment induced increased zymogen depletion and also the development of large basal vacuoles in many acinar cells. At the ultrastructural level, acinar cells show pronounced mitochondrial swelling, which in many instances is accompanied by the development of myelin whorls. The number of cells with distended granular endoplasmic reticulum is increased as is the number of atrophying cells and cells apparently undergoing disintegration. In addition, there are indications of marked activation of interlobular perivascular macrophages which show marked vacuolation. Our observations suggest that pancreatic acinar cells show cytological changes as a result of experimental hypercorticoidism.


Correlations between tooth dimensions of man and apes. Computation of simple, multiple and canonical correlation coefficents between the mesiodistal and buccolingual crown diameters showed a high degree of association between the overall crown dimensions of man and chimpanzee. Information regarding the partitioning of genetic and environmental influences on crown form must therefore await further data regarding the degree of correlation between detailed intra-crown dimensions. Nevertheless, the data from this study suggested that dentitions should be regarded as whole biological entities rather than a series of discrete teeth.


Ultrastructural data and chronobiological patterns of the synaptic ribbons in the outer plexiform layer in the retina of albino rats. Synaptic ribbons of the outer plexiform layer in the retina of albino rats are examined, with particular regard to their ultrastructure and to their chronobiological behaviour. As to the ultrastructure, aside from the typical lamellar and granular morphology, synaptic ribbons, whose central bar is roundish and granular, delaminate or furnished with enlarged extremities, are shown. As to the chronobiological pattern, synaptic ribbons undergo to circadian changes in their absolute number, being particularly numerous during the light phase, and few during darkness. It is also considered the morphology (ratio between granular and lamellar) and the size (long, intermediate and short) during the 24-hour cycle; in both cases, diphasic curves are observed. On the basis of these results, in the junction photoreceptors-bipolar cells, synaptic ribbons are polymorphic, dynamic structures, whose number and morphology strictly depend on environmental light conditions.


Positional relationships of structures attached to long bones during growth. Cross-sectional studies. The various soft structures attached to bones maintain relatively constant relationships during growth. The exact number of these relationships has, however, never been studied. As part of our ongoing research into the factors controlling muscle migration, we have determined these relationships for some structures. We studied the positions of 37 muscles from 24 New Zealand white rabbits ranging in age from birth to maturity. The muscles were selected to illustrate different kinds of attachments: fleshy and tendonous, restricted and extensive, and at both ends of a bone. The proximal and distal edges of attachments were carefully exposed and measured in a device that allowed us to measure the position relative to the ends of the bones without parallax distortion. We used the data to compute correlation coefficients and regression equations for position vs. length of bone. Results show that the correlation coefficient was above 0.9 for most cases and was significant at the 0.5 level for all but 4 cases. Slopes of the regression equations varied considerably, but in all cases they indicated that the closer to the end of a bone, the greater the distance migrated. The significance of these results is discussed.


New capillary collagen of cutaneous scars. The capillary collagen of several human keloids was studied. In the majority of the preparations, the collagen had the appearance of an amorphous mass where the amorphous material of the intercellular component was mixed with the newly formed collagen. The vessels of these regions offered neither definite form nor structure but rather a mixture of well-formed fibers and of other fibers still in the process of formation. The principal characteristic of the newly formed vascular collagen was its distribution in the form of rings, each of which was united in turn to other rings. Fibers could be seen radiating from the periphery of these rings and served to join the rings to the surrounding intercellular amorphous substance. The vessels presented different disposition and structures depending upon their grade of development, which is never complete.


Sexual dimorphism of skeletal robusticity in several mammalian orders. This study tries to determine whether a phylogenetic trend exists in the sexual dimorphism of skeletal robusticity and whether domestication has an effect on it. The problems were studied in the metatarsals of marsupials, insectivores, rodents and primates including Homo, and in various skeletal sections of wild and domesticated rats and dogs. No clear phylogenetic trend could be found and domestication cannot be shown to have an effect on diminishing skeletal robusticity. Sexual dimorphism of skeletal robusticity seems to be highly species-specific and to have a mosaic distribution in a given taxon. Conclusions on phylogenetic trends of sexual dimorphism of skeletal robusticity and the effect of culture on it seem to be premature.


Ultrastructural evidence of thin intercapillary anastomoses in the renal glomerulus. Electron-microscopic examination of mouse kidneys revealed in the glomeruli very thin (0.7 micron) vessels, the wall of which has the same structure as the remaining glomerular capillaries. The authoress considers them intercapillary anastomoses which were detected already previously by injection with India ink, however, the structure of their wall was not known hitherto.


Atypical thyroid follicles arising from an ultimobranchial-like cyst in a postnatal canine thyroid gland. While investigating the intrinsic vasculature of the canine thyroid gland, atypical thyroid follicles were observed histologically, arising from a postnatal thyroid cyst of unknown origin, in stained sections of a male, 1-year-old, mesaticephalic dog. The animal was anesthetized, bled, killed by injection of Toxital directly into the heart, and perfused with 10% buffered neutral formalin solution. The thyroid tissue was fixed, embedded in paraffin, sectioned serially, and mounted on glass slides. Concordant with descriptions in the literature, this structure appeared to be a postnatal ultimobranchial-like cyst with direct connections to both ultimobranchial and mixed follicles. Seemingly, this observation has never been reported previously in the canine and would lend support to the hypothesis that ultimobranchial-like cysts may give rise to these atypical follicles. However, the authors are not totally convinced that all such thyroid cysts are solely ultimobranchial in orgin. A review of the literature supporting this contention is discussed.


Functional and hormonal control of pelvic width in the rat. Absolute sacral dimensions of the rat are influenced by muscular, ovarian and testicular action, and all affect absolute sacral length more than absolute width. However, relative to trunk-length dimensions are rather stable and drop with a higher level of significance only in castration combined with estrogen or progesterone treatment. Relative pelvic width, as expressed by the transverse interiliac distance, is greatly widened in extreme muscular hypofunction but the sacrum does not participate in this widening. The widening results from a broadening of the proximal part of the ilium, following a genral response of long bones to extreme muscular hypofunction. Pelvic width is reduced in castration and ovariectomy with and without testosterone or estrogen treatment, but not in the combination of castration with progesterone treatment. Changes of sacral width are, however, more often independent from than concomitant with the width changes of the pelvis. The transverse interventral spine distance is dependent on rectus femoris muscle activity and drops drastically in hind-leg removal. It also drops in castration and particularly when castration is combined with estrogen treatment; but progesterone adds little to the effect of castration alone. The effect of ovariectomy alone or combined with testosterone treatment is negligible.


Association of mitochondria with the plasma membrane of the acinar cells of the mouse submaxillary glands1. Electron micrographs of resting and pilocarpine-stimulated acinar cells of mouse submaxillary glands revealed the majority of mitochondria in close association with lateral and basal portions of the acinar cell membranes. The qualitative observations were confirmed by quantitation. Speculations as to the functional significance of this observation are discussed.


Clinical aspects and long-term prognosis in supratentorial tumors of infancy and childhood. A total of 132 children, less than 15 years of age at the time of diagnosis of an intracranial supratentorial tumor, were followed from 1 to 40 years. The patient material was unselected and the follow-up 100%. 73 were boys and 59 were girls. The tumors were located in the lateral region of the brain in 70 children and in the midline in 62. Astrocytoma was the most common histological type, followed by craniopharyngioma. The occurrence of the most malignant tumor types was significantly higher in the lateral than in the midline region. 84 children survived for more than 1 month after the initial diagnosis or surgery, and 29 of these were alive 15 to 40 years after operation. 45% of the children with tumors situated laterally and 30% of those with midline tumors were alive after 15 years. 14% of those who survived at least 15 years had severe and 34% slight neurological defects.


Clinical features and long-term follow-up of patients with reversible ischemic attacks (RIA). The clinical features of 102 cases with transient attacks due to cerebral ischemia were evaluated, and 94 out of 102 cases were followed for an average of 6 years. 1) The clinical study makes comparisons between two groups of patients grouped under the somewhat new definition of Reversible Ischemic Attacks (RIA): classical Transient Ischemic Attacks (TIA) and Stroke with Full Recovery (SFR), in which a complete recovery took place over a longer period, on the average 3 weeks. 2) SFR constitutes the 34.31% of the total cases with transient ischemic episodes. In the carotid district the onset was more frequently gradual in SFR than in TIA and aphasia more frequent in TIA than in SFR. Multiple attacks prevailed in TIA over the SFR group. The definition of transient attack due to ischemia is discussed. 3) Completed strokes occurred in 11 cases (11.7%) with RIA. Hypertension and cardiac disease were significantly frequent in cases with subsequent stroke. The conclusion was reached that TIA is a symptom, not a pathological state, and TIA should be considered an important symptom but not a specific harbinger of completed stroke.


Osteoarthropathy of hepatolenticular degeneration. Ninety-six joints of 25 patients with hepatolenticular degeneration have been studied by means of scintigraphs with technetium (99mTc), a method which can disclose early synovial inflammation and postinflammatory articular degeneration. Signs of synovitis were found in 22 joints of 10 patients (40%) and degenerative changes were present in 15 joints of eight patients (32%). Eleven patients complained of joint pains; in four of them they were the presenting symptom. The radiological study showed osteoporosis in 22 patients (88%); flexion deformity was found in two cases, anomalous osteophytes in two, and signs of growth arrest, features of rheumatoid arthritis and aseptic necrosis in one case each. The pathogenesis of osteoarticular changes in Wilson's disease is discussed.


Morphological, biochemical, ultrastructural, tissue culture and clinical observations of typical and aggressive craniopharyngiomas. Craniopharyngiomas are tumors of the suprasellar area, which are often cystic, encapsulated and slow-growing. Certain of these tumors can behave in an aggressive manner and either invade surrounding structures or recur. In order to determine characteristics which may aid in distinguishing typical from atypical lesions, a study of biopsy and tissue culture specimens from 25 human craniopharyngiomas was undertaken. Tissue culture observations reveal two distinct cell populations. Typical lesions grew in culture in an orderly epithelial pattern and had desmosome-tonofibril aggregates and smooth surface topography demonstrable by electron microscopy. In the atypical tumors the cell growth was irregular, with mitotic activity, cholesterol crystals and features characteristic of neoplastic transformation, such as surface microvilli, an increase of cytoplasmic basophilia, size and number of nucleoli and retraction of cytoplasm. Correlation with the clinical status of the patients suggests that tumors of the four patients which exhibited atypical features in culture behaved more aggressively.


Heterotopic brain tissue in the submandibular region and lung. Report of two cases and comments about pathogenesis. Two cases of extracranial heterotopia of the brain are reported. Case 1, in an otherwise normal female baby, had a brain heterotopia in the submandibular region. Case 2, in a still-born female baby with anencephaly, had the heterotopia in the lung. The lesion in case 1 is believed to be an encephalocele that has been pinched off through a cleft in the bone or through a foramen of the skull; the pathogenesis is similar to that of the so-called "nasal glioma". Concerning the pathogenesis of case 2, contrary to the generally supported embolism theory, observation of serial sections of the tumor in the lung favors the aspiration theory according to which amniotic brain tissue fragments, which are dislocated into the amnion because of nonclosure of the ventricle or following destruction of the fetal brain, are aspirated by fetal respiratory movements in the 4th to 6th month of intra-uterine life.


[Effects of thyroid hormones and heat value restriction of food intake on the glial surrounding and soma development of Purkinje cell (author's transl)]. Hyper- and hypothyroidism repercussions on soma, nucleus and cytoplasm increases were studied by electron microscopy on 7-, 14-, 21-, and 35-day-old rats. Adult normal animals were compared with adult ones made hypothyroid until they were 35 days old. Also heat value restriction of food intake effects were compared with hypothyroid ones at 14 and 35 days. Hyperthyroidism accelerated the soma and cytoplasm size increase as early as 14 days, and the nucleus size increase as early as 21 days. It did not change the nucleo-cytoplasmic ratio (N/P) markedly, except that maximal value of this ratio was reached earlier than in normal animals. Heat value restriction of food intake led to a transitory soma size decrease at 14 days and a high nucleus size increase. This diet did not change markedly either cytoplasm size or N/P ratio value. Hypothyroidism slackened the rate of the soma, nucleus and cytoplasm size increase during the third postnatal week especially. Beyond, these structures went on increasing and their size became greater than normal in adult hypothyroid animals. N/P ratio was always superior to normal. Hypothyroidism led to a high volumetric and linear density of Purkinje cell soma glial surrounding. Hyperthyroidism caused a slight increase of these parameters which were not greatly changed by heat value restriction of food intake.


Canine distemper virus-associated encephalitis: modification by passive antibody administration. Gnotobiotic puppies were intraperitoneally infected with R252-canine distemper virus (CDV), and treated with normal serum (NS) or CDV-specific antibody. Resultant central nervous system (CNS) lesions were evaluated by light and immunofluorescence microscopy. Lesions in NS-treated dogs, if present, consisted of small foci of neuronal degeneration and accompanying microgliosis, restricted to grey matter of the frontal lobe. Dogs receiving anti-CDV antibody, in contrast, had extensive lesions in the brain. Laminar cortical necrosis, gliosis and astrocytic activation of the grey matter of the frontal lobe was the most consistent lesion observed. In addition, foci of cerebellar granule cell layer degeneration and necrosis was seen along with segmental poliomalacia of the spinal cord. In several dogs, eosinophilic intracytoplasmic and intranuclear viral inclusion bodies were observe in neurons. The lesions observed in these dogs are compared to previously reported lesions of CDV infection in dogs.


Reactivity patterns of nerve cell-glia-complexes in mice during pentylenetrazole-induced seizures. Cytometric-cytophotometric studies. The relationships between nerve cell-glia-complexes (NGCs) and surrounding capillaries were studied by combined cytometric-cytophotometric methods in male mice up to 60 min after injection of 70 milligrams/kilograms of pentylenetetrazole (PTZ). The nuclear area in neurons from cortical layers IV and V of the motoric area 8 increased by 13%, and in neurons from the hypoglossal nucleus there was an increase of 23%, associated with phasic changes in the nuclear area of their glial satellites. The number of perfused capillaries increased in both brain regions and there was a 20%-elongation of erythrocyte-filled capillary segments. The cytoplasmic RNA content enlarged in the hypoglossal neurons but decreased in cortical neurons from area 8. Peptidergic neurons and their glial satellites (supraoptic nucleus) showed nuclear shrinkage. Fifty percent of these peptidergic neurons reacted by reduction of their cytoplasmic RNA content. The measured cell reactions seem to be specific for different groups of NGCs which were defined by their histotopography, their neuronal interconnections, and a prevalence of secretory or nonsecretory neurons.


Morphological demonstration of the virus of tick-borne encephalitis in the human brain. A case is presented in which the fourfold increase of the HI titer during the progression of the disease, and an increase in IgM content found at the beginning of the second week of the disease confirmed the diagnosis of tick-borne encephalitis. The light microscopic changes correspond to the findings accepted as characteristic to tick-borne encephalitis. Viruses, morphologically belonging to the Flavivirus genus were found by electron microscopy in the thalamus, substantia nigra, and cerebellum of the dissected brain. This paper presents the first demonstration of the virus in a case of a human tick-borne encephalitis.


Megalencephaly and chromosomal anomaly.

Megalencephaly and chromosomal anomaly. A 6-year-old mentally retarded boy died after cardiac surgery for Fallot's tetralogy. The brain was of enormous size, weighing 2230 grams and showing widespread polymicrogyria and dysdifferentiation to regular large pyramidal neurons without increased DNA content. Nuclear Barr bodies indicated a XXY-chromosomal (Klinefelter) syndrome, which has not been previously reported in megalencephaly. True megalencephaly (excluding the symptomatic forms) should remain a pathological diagnosis and restricted to cases with an abnormally high brain weight in addition to morphological alterations. There is evidence for a genetic base in many cases of megalencephaly, and chromosomal studies may yield more information in this respect


CAP, HCS and urinary oestriol assays in diabetic pregnancy. The value of serial estimations of plasma CAP, HCS and urinary oestriol assays in pregnancies complicated with diabetes has been studied. The material consists of 31 patients, 16 of whom delivered normal infants and 15 delivered newborns with diabetic foetopathy. It is concluded that the levels of CAP, HCS and urinary oesteriol excretion in diabetic pregnancies are comparable to those found in normal pregnancy. No significant differences in the biochemical parameters were detected between diabetic women who delivered infants with foetopathy compared to diabetic women who delivered normal infants. The maternal oestriol excretion was, however, somewhat higher in diabetic women who delivered infants with macrosomia.


Ultrastructure and variations of human cervical mucus during pregnancy and the menopause. Ultrastructural aspect and variations of cervical mucus have been studied by scanning electron microscopy in 58 pregnant and 29 menopausal women. In both groups, a striking tightening of the ultrastructural glycoprotein framework was demonstrated. The phenomenon appears to occur very rapidly at the beginning of pregnancy while patients near the menopause show more variable patterns. The results are compared to the known evolution of cervical mucus ultrastructure during the ovarian cycle and discussed from a rheological point of view. Particular attention was paid to the eventual antibacterial role of cervical mucus in pregnancy, which was found to be very plausible.


Fracture and chemical composition of the deposit formed on the Lippes loop after prolonged use. In order to confirm or refute the theory that there is the need to replace IUD's every few years due to their breaking, 26 Lippes Loops were tested. The sediment found on the devices was composed mainly of calcium carbonate. After removal of the sedimentation, it was seen that there was some corrosion of the body of the devices which caused a decrease in the IUD thickness. Pressure tests showed that an IUD which has been in use for a long period of time is more rigid, has less ability to deform and breaks under less pressure. It seems that the current medical opinion stating that IUD's should be replaced every few years, is valid.


Cryosurgical treatment of dysplasia and carcinoma in situ of the cervix uteri. Fifty-nine patients (age range 18-40 years, mean 28 years) with dysplasia or carcinoma in situ of the cervix uteri were treated with cryosurgery. Healing occurred in 54 patients (91.6%) after one treatment ("double-freeze" technic) and in 2 patients after refreezing. No early or late complications occurred during a follow-up period of 7-37 months. Five of the patients with carcinoma in situ were followed immunologically with determinations of serum TPA (tissue polypeptide antigen), which can be employed as a parameter of malignancy. In all instances, the initially elevated TPA normalized after cryosurgical treatment. Cryosurgery is a simple, painless and safe treatment method in ectocervically localized carcinoma in situ and dysplasia that is particularly suited for out-patient use.


Human placental lactogen levels in amniotic fluid in normal and toxemic pregnancies. Amniotic fluid human placental lactogen (HPL) levels were measured by radioimmunoassay in 162 cases of women with normal pregnancy and 43 with toxemic pregnancy, in the last trimester of pregnancy. A significant differences in levels was observed.


The site of placental attachment as a factor in the aetiology of breech presentation. The frequency of cornu-fundal implantation of the placenta in association with breech presentation was investigated in the following study. In a series of 124 women with breech presentation, and 125 women with cephalic presentation at or near term, the implantation site of the placenta was demonstrated by ultrasonography. It was found that with breech presentation the placenta was implanted in the cornual region in 72.6% of the cases, as compared with 4.8% in cephalic presentation. The placental implantation site may therefore have a determining effect upon the presentation of the foetus.


Pregnancy in a case of Nelson's syndrome. A woman suffering from Cushing's disease from the age of 17 who had been treated consecutively with pituitary irradiation, bilateral partial adrenalectomy and o,p'-DDD (Mitotane, USP) presented the clinical picture of Nelson's syndrome (hypoadrenalism with secondary hypersecretion of ACTH and MSH) at the age of 32. Under substitution therapy with corticoids she became pregnant for the first time at the age of 38. The course of the pregnancy was normal and at term she was delivered of a normal child by Cesarean section. The materno-fetal relationship, the increased risk of pituitary infarction during pregnancy and the possible teratogenic effect of chemotherapy in such cases are discussed.


The Landry-Guillain-Barré syndrome and pregnancy. The Landry-Guillain-Barré syndrome is considered rare in connection with pregnancy. In mild cases the course of the pregnancy is unaffected. In severe cases, with respiratory depression and bulbar symptoms, especially during late pregnancy, the syndrome entails an increased risk to both mother and foetus. Therapeutic abortion of cesarean section are not considered to be indicated. A pregnant woman developed the disease during the final trimester and gave birth to premature twins during respirator treatment. The mother and the infants survived.


Recurrent hydatidiform mole. Report of a case with five recurrences. A report on a patient having five consecutive molar pregnancies is presented. None of the pregnancies was associated with a fetus and all five hydatidiform moles  were histologically benign. The treatment of recurrent moles is discussed and the literature concerning this problem is reviewed.


Implantation of a scleral strip into the supraciliary space and cyclodialysis in glaucoma. Since 1975 the operation of implantation of a scleral strip (10 mm long and 2 mm wide) has been performed on 75 glaucomatous patients. The following variants of surgical technique were used: (1) implantation of an autoscleral strip into the supraciliary space, (2) implantation of an autoscleral strip combined with cyclodialysis and (3) implantation of a homoscleral (cadaver) strip combined with cyclodialysis. The first technique was employed in 12 cases. The intraocular pressure was controlled by surgery alone in only four eyes, though a decrease in the level of the intraocular pressure and an increase in the C-value occurred in each case. No significant difference between the results obtained with the second and the third techniques was found. Of 63 eyes operated on, the intraocular pressure was controlled in 41 eyes (65%) by surgery alone and in 11 other eyes with the help of miotics 3 to 4 weeks after surgery. Follow-up was for a period of from 12 to 23 months in 51 cases. The pressure was under control in 36 eyes (71%) without medication and in 10 more eyes with miotics. The rate of complications was low. Hyphaema appeared in 10 cases and mild iridocyclitis occurred in 11 cases. There was no case of choroidal detachment, persistent hypotony or flat anterior chamber after surgery.


The ultrastructure of the human lens capsule. I. Cataractous lenses from eyes with simple glaucoma. A transmission electron microscopic study. The lens capsules from five cataractous lenses removed from eyes with glaucoma simplex have been compared with capsules from five cataractous lenses removed from eyes without glaucoma. Glaucoma simplex, cataracta senilis or the treatment of the glaucoma by drug therapy or surgical intervention do not seem to influence the ultrastructure of the lens capsule. The findings are identical with those observed in the normal aging human lens.


The ultrastructure of the human lens capsule. II. Cataracta complicata. A transmission electron microscopic study. Eight human cataractous lenses extracted from eyes suffering from uveitis have been examined by transmission electron microscopy. The following changes have been demonstrated: cellular proliferation, fibrillogenesis and formation of osmiophilic, electron-dense amorphous structures. The changes were most pronounced in young lenses but had no features in common with the FEC (fibrillopathia epitheliocapsularis) syndrome.


The existence of smooth muscle adjacent to the Schlemm's canal of the normal albino rat eye. The existence of smooth muscle adjacent to the rat aqueous outflow pathway was confirmed in this study. The smooth muscles ran parallel to the Schlemm's canal and reached the level of the posterior end of Schlemm's canal. The characteristics of these muscles were similar to smooth muscles in other organs. The existence of smooth muscle in this region depends on the fact that the rat eye lacks the scleral spur and the poorly developed meridional fibers of ciliary muscles come to lie close to the endothelial cells of Schlemm's canal. The innervation and function of these smooth muscles are unknown.


Secondary haemorrhage following traumatic hyphaema. A comparative study of conservative and tranexamic acid treatment. Three out of 56 consecutively admitted patients with traumatic hyhaema, treated conservatively, developed secondary haemorrhage. Of the following 64 patients treated with tranexamic acid, none developed secondary haemorrhage. Statistical analysis, using chi2 test with Yate's correction showed no statistical difference with regard to the occurrence of secondary haemorrhage between the two groups.


Vitreo-scleral fluid transfer in the rabbit. Experiments were carried out to see whether a radioactive tracer placed in the vitreous of a rabbit eye could be detected on the sclera. A solution of Xenon-133 dissolved in saline was injected into the vitreous of six rabbits and collecting tubes containing activated charcoal were placed on the sclera. The presence of Xenon in these tubes confirmed that vitreoscleral transfer had occurred. It was calculated that on average, 2% of the Xenon had appeared over the whole sclera. A mathematical analysis of the shape of the activity curve of the tracer on the sclera revealed that its appearance was probably due to diffusion across the outer layers of the eye.


Amino acid transport in human ciliary epithelium. A statistical study of the co-variation of the concentrations of 19 amino acids and related compounds from 21 persons was performed as a factor analysis of Caq/Cpl and of Caq. Six factors explained about 83% of the observed variation. Factor 1 showed a correlation to alpha-amino-N-butyric acid, valine, methionine, isoleucine, leucine, tyrosine and phenylalanine, factor 2 to lysine, histidine, arginine and glutamine (containing serine), factor 3 to taurine and proline, factor 4 to glycine and cystine, factor 5 to urea and factor 6 to glutamic acid. Only alanine and threonine showed a correlation to different factors in the Caq/Cpl- and the Caq-matrix. This correlation of groups of substances to different and independent factors is considered to be an argument in favour of the existence of six transport systems in the ciliary epithelium for the investigated substances.


Fluorescein angiography of the iris. A correlation of microangiopathy in the iris and retina. Fluorescein angiography of the iris using filters that eliminated pseudofluorescence was performed. In 10 of 40 non-diabetic healthy eyes, a fine-grained leakage of dye occurred from capillaries of the pupillary margin (PML). In 87 of 94 diabetic eyes with or without retinopathy a PML was present. The vascular changes of the iris were compared with those of the retina as disclosed by fundus fluorescein angiography. In 14 of 18 eyes without retinopathy PML was observed. In 25 of 28 eyes with non-proliferative retinopathy there was a PML, 12 of those in addition showed extravasation to the iris stroma. All 48 eyes with proliferative retinopathy showed PML. In addition, 19 of these had extravasation to the iris stroma and 26 iris neovascularization. When iris neovascularization is present, larger fibrovascular proliferations are usually found in the vitreous space, often associated with recurrent vitreous haemorrhages or retinal detachment. Iris angiography yields valuable information on the vitreo-retinal diabetic sequelae and is useful for selection of such eyes for vitrectomy.


Pulfrich pendulum phenomenon in patients with a history of acute optic neuritis. The Pulfrich phenomenon is a stereoillusion in which a pendulum swinging at right angles to the line of gaze appears to be describing an elliptical path when absorbing filters are placed in front of one eye. We used two sets of polaroid glasses as adjustable filters. A spot on a modified oscilloscope served at a pendulum bob. Twenty-nine former patients with a history of optic neuritis and visual acuities of greater than or equal to 6/6 in both eyes and twenty-two normal subjects underwent examinations. The patients showed pathological recordings which separated them from the control subjects. The test seems to expose minor residual dysfunction of affected optic nerves where the visual acuity is normalized. This abnormal response when viewing the moving Pulfrich pendulum is probably caused by disturbed neural conduction. The degree of acute visual loss and the time elapsed since the attack did not seem to influence the Pulfrich response. The results may explain why some patients who have recovered from optic neuritis complain of difficulties when viewing moving objects. In addition to the use of Pulfrich illusion test for diagnostic work; i.e. clinical or subclinical attacks of optic neuritis, it can serve as a valuable supplement to the more sophisticated method of visual evoked response.


The c-wave of the human electroretinogram in central retinal artery occlusion. The pigment epithelium-receptor complex, which is supplied from the choroidal circulation, is the main source of the c-wave of the ERG. Occlusion of the central retinal artery (OCRA), which causes serious damage to the inner retinal layers, should therefore not primarily be expected to affect the c-wave amplitude. Nevertheless, conflicting reports of increased, decreased and unchanged c-waves have appeared in the literature. In the present study on four patients with OCRA the affected eyes showed diminished b- and c-waves. On the other hand, both the a-wave and the trough between the b- and c-waves were accentuated in the diseased eyes. Experiments in progress on Cynomolgus monkeys with experimentally induced unilateral OCRA show similar results.


Malignant melanoma of the conjunctiva and the iris in a case of primary acquired melanosis of the conjunctiva. A case of primary acquired melanosis of the conjunctiva is reported. During the 18 years of observation the patient developed a malignant melanoma in the iris, and seven years later a malignant melanoma appeared in the lower lid. The iris melanoma may be an extension from the precancerous melanosis, but the most likely explanation is that the condition represents two independent diseases.


Simultaneous traumatic posterior dislocation of both hips. A case report. Simultaneous traumatic posterior dislocation of both hips, uncomplicated by fracture, is an exceptionally rare entity. The authors could not find any record of a similar case in the world medical literature up till now, and are therefore reporting this case with special consideration of the mechanism of injury and the management.


Effect of indomethacin on collagen metabolism of rat fracture callus in vitro. The collagen metabolism of callus tissue from closed, non-immobilized rat femoral fractures was studied in vitro after in vivo treatment with indomethacin 2 mg/kg/day for 6, 9 and 12 days after fracture. Total hydroxyproline synthesis and incorporation of hydroxyproline into collagen were found to be significantly increased after indomethacin treatment, whereas no significant difference was found regarding collagen resorption. The results suggest that the recently demonstrated inhibition of fracture healing by indomethacin is not brought about by an inhibition of collagen synthesis.


Glycosaminoglycan metabolism in experimental osteoarthrosis caused by immobilization. A study was made of glycosaminoglycan metabolism of articular cartilage in developing experimental osteoarthrosis caused by immobilization of the rabbit knee. Cartilage samples from various sites in the knee and hip joints were analysed, samples from the mobile limb serving as controls. The concentration of glycosaminoglycans in the tissue was measured by determinations of hexosamine and uronic acid after prior papain proteolysis and subsequent purification. The uptake of 35S-sulphate was used as an indicator of the synthesis rate of sulphated glycosaminoglycans. Metabolic changes characteristic of osteoarthrosis, i.e., glycosaminoglycan depletion and increased uptake of 35S-sulphate, were found in tibial weight-bearing and femoral condylar cartilages. Net synthesis of glycosaminoglycans occurred in the tibial marginal cartilage.


Compression of the suprascapular nerve after fracture of the scapular notch. A 32-year-old man with a fracture of the scapular notch associated with a lesion of the suprascapular nerve is reported. A nerve decompression operation was performed 20 months after the injury with relief of pain. The possibility that residual disability following a fracture of the scapula can be due to a lesion of the suprascapular nerve is underlined. The value of X-ray examination with projections visualizing the notch and diagnostic local anaesthetic block of the nerve passing through the notch are emphasized. Primary wide resection of the scapular notch is a preferable procedure preventing recurrence of nerve compression symptoms.


Operative treatment of scoliosis with Harrington instrumentation technique. Thirty-five patients with scoliosis were treated with posterior fusion including the Harrington instrumentation technique. The operation was followed by a 1-year period of treatment in a Milwaukee brace. The patients had a thoracic or a thoracolumbar curve averaging 74 degrees. The mean initial correction was 45 per cent, and the mean final correction 33 per cent, after 2 3/4 years. There were no cases of pseudarthrosis and only one case of transient paresis. There were no deaths. It is concluded that these results are satisfactory and that the method is a safe one in experienced hands.


Postural equilibrium in adolescent idiopathic scoliosis. Postural equilibrium has been quantified by stabilometry in 57 patients with adolescent idiopathic scoliosis aged 10-16 years. Treatment was required in 39 cases whereof 18 were placed under observation only. The control group comprised 32 healthy children of the same age. An experimental design was made to vary the degree of difficulty of upright standing in four different test situations. The postural sway was analysed in the sagittal and lateral direction as well as in the area of total sway. The scoliotic patients had a significantly poorer postural control compared with the healthy children in all the tests. The difference was most pronounced in tests in which the proprioceptive functions were most important for maintaining the postural equilibrium. The left convex patients had quantitatively more pronounced reactions than the right convex patients. Patients with small curvatures, i.e., patients placed under observation only, had significantly increased postural sway compared with patients with more severe deformity. This fact, together with findings in patients with double primary curvatures, and the results of the study of brace effects, indirectly indicate the possibility of a postural disequilibrium as a contributory causative factor in adolescent idiopathic scoliosis.


A rational approach to the use of epidural medication in the treatment of sciatic pain. The results of a series of 120 epidural injections given as treatment for backache and sciatica using Methylprednisolone and local anaesthetic, performed in the Gloucestershire area, are presented and compared with other published results. Wide variations in the results of this treatment are found and these may in part be explained on the basis of the variable severity of the histological changes known to occur in and around nerve roots in cases of sciatica. The pathogenesis of sciatica in lumbar disc disease is discussed in relation to its treatment by epidural injections of a long-acting steroid. It is shown that the treatment is more successful in acute onset cases and cases that have epidurals within 6 months of the onset of symptoms and it is suggested that earlier epidurals are given in cases that do not respond to the usual conservative measures. Manipulation of the spine and sciatic stretch should not be carried out at the same time as the epidural, as these procedures may adversely affect the results in some cases and certainly tend to make them more difficult to assess.


Hip joint instability after the neonatal period. Diagnosis and treatment of 20 consecutive cases. A consecutive series of 20 children (21 hips) with idiopathic hip joint instability, diagnosed after the neonatal period, is presented. The diagnosis was confirmed by hip joint arthrography. In all the children, 1.5-21 months old at the time of diagnosis, closed reduction could be achieved. They were treated in plaster directly or after treatment of contractures in the adductor muscles of the hip joint. Stability was rapidly attained during plaster treatment. The results of the treatment in plaster were checked by a second arthrography in two thirds of the cases, and all cases have been clinically and radiologically evaluated 1-4.5 years after diagnosis. All of the children developed clinically stable hips and they walk normally. In two hips signs of avascular necrosis of the femoral head were found and in three hips (two children) the skeletal development was markedly delayed. In 81 per cent (17/21 hips) the prognosis was considered good; it is uncertain in the remaining four hips. The appropriate period of fixation in plaster related to the age of the child is discussed.


Evaluation of painful hip arthroplasty.

Evaluation of painful hip arthroplasty. The evaluation of chronic pain after hip arthroplasty has always been a difficult problem and recently scintigraphy has been recommended as a suitable method of examination for this purpose. On the basis of radiographic and laboratory studies, scintigraphy, allergy tests, cultures and histological examinations, in 16 patients with chronic pain in the hip after arthroplasty, it is concluded that radiography and scintigraphy together give valuable information about the cause of pain, especially if the prosthesis is infected. Fenestration of the femoral cortex may verify the diagnosis before replacement of the prosthesis.


Secular tendencies of the incidence of fracture of the upper end of the femur. On the basis of an epidemiological study of the incidence of fracture of the upper end of the femur, undertaken in the city of Malmö for the period 1951-1960, the expected number of fractures in 1967 and 1968, and in 1974 and 1975, was calculated taking into account the changes in the size and the composition of the population. It was demonstrated that during the first period the previously described increasing trend continued so that more fractures were observed than could be expected from changes in the population only, whereas later on this trend became insignificant. The changes observed after 1968 could be explained by the increasing number of old residents in the city, and there was no obscure secular trend.


Unstable trochanteric fractures treated with the sliding screw-plate system. A biomechanical study of unstable trochanteric fractures. III. Eighty unstable trochanteric fractures were treated with the sliding screw-plate system. Early weight-bearing was encouraged and mobilization was obtained within the first week in 47 per cent of the cases (37/78). Technical complications were encountered in 5 per cent of the patients (4/76) but none required re-operation. Telescoping of the screw occurred in 49 per cent (37/76). Through this secondary fracture impaction a stable load transmission system was established. Fracture union in the postoperative position was obtained in 49 per cent of the patients (37/76) and non-union did not occur.


Findings at arthroscopy and arthrography in knee injuries. The diagnostic accuracy of arthroscopy and arthrography was investigated. A total of 135 patients were examined by the two methods. All were operated on and 90 of them were analyzed in detail, the X-ray examinations being done at this hospital. In 82 patients arthroscopy gave correct information. In eight (9 per cent) the diagnosis was incorrect, in most cases a rupture of the posterior horn of the medial meniscus being overlooked. Arthrography gave accurate preoperative information in 52 patients, but in 38 (42 per cent) the diagnosis was inaccurate. This difference in correlation with the operation findings between arthroscopy and arthrography was highly significant (P less than 0.001), and it is concluded that endoscopy gives more complete and more useful preoperative information than arthrography. Arthrography, however, remains a valuable diagnostic tool, as arthroscopy cannot be performed in every patient with knee symptoms.


Responses of auditory nerve fibres to noise stimuli show cochlear nonlinearities. The frequency selectivity of the peripheral auditory frequency analyser was determined on the basis of recordings from single auditory nerve fibres in the rat, using pseudorandom noise as stimulus. The impulse response function was arrived at by cross-correlating period histograms of the recorded activity with the noise. Frequency transfer functions were computed by Fourier transformation of the derived impulse response function. The impulse response function was observed to become shorter with increasing stimulus intensity. A concomitant widening of the frequency transfer function and a downward shift in the centre frequency were seen. Since the method used is insensitive to nonlinearities, the derived impulse and frequency respone functions are assumed to be valid approximations of the basilar membrane properties. The results, then, support the hypothesis that the basilar membrane is a nonlinear frequency analyser whose selectivity decreases as sound intensity increases.


Computer analysis of optokinetic nystagmus in patients with spontaneous nystagmus of peripheral vestibular origin. The bias of slow phase velocity (SPV) of optokinetic nystagmus (OKN) caused by an acute labyrinthine lesion was examined in 8 patients using differnet optokinetic stimulus velocities. In all patients a directional preponderance of OKN-SPV was found corresponding to spontaneous nystagmus. This was due to enhancement of nystagmus SPV to the side of the lesion and depression of SPV in the opposite horizontal direction. The preponderance of OKN on the average increased with the intensity of spontaneous nystagmus and decreased along with recovery. These vestibularly induced differences in OKN-SPV range up to 70%. A differentiation is discussed between OKN preponderances caused by labyrinthine lesions and brain stem lesions.


Vertigo as reflected by the nystagmogram. A clinical analysis. Efforts to evaluate findings in the nystagmogram were made in a material of 338 vertiginous and dizzy patients. A spontaneous nystagmus, a positional nystagmus as well as a difference in caloric reactivity are as solitary findings of lettle value for revealing peripheral disorders. On the other hand, central disturbances are frequently revealed by inability to track a moving optic target, resulting in an irregular or a saccadic pattern, by persistence of vestibular nystagmus in light, by persistence of such nystagmus at eye-closure, by an increase in spontaneous nystgmus on eye-closure or by dysrhythmic nystagmus in caloric tests. Cases of functional vertigo seem to differ from cases of vertigo from other sources by their increase of spontaneous nystagmus (when present) or by persistence of caloric nystagmus on eye-closure.


Nasal mucociliary function during penicillin treatment. Nasal mucociliary function was studied in 21 healthy subjects before, during and after penicillin administration. No change in the mucociliary function occurred during penicillin treatment. Nor was any difference observed between men and women or between smokers and non-smokers. On the other hand, the measurements revealed a significantly smaller intra-individual than inter-individual variation. As the epithelia of nasal cavity and Eustachian tube are morphologically of the same type it is concluded that the increased incidence of serous otitis media which has been observed after the introduction of penicillin in the treatment of acute otitis media can scarcely be due to an inhibitory effect of penicillin on the mucociliary function of the Eustachian tube.


A possible involvement of acidic glycosaminoglycans in kanamycin ototoxicity. The content of acidic glycosaminoglycans (AGAG) was determined quantitatively by electrophoretic microanalysis in the cochlea, kidney and brain of the guinea pig. Kanamycin treatment (400 mg/kg body weight/day, i.m., 10 successive days) reduced the content of AGAG markedly in the lateral wall of the membranous cochlea. Furthermore, from the results of the ultrahistochemical and freeze-fracturing study, we propose here an "excretion system for basic aminoglycoside antibiotics" by means of the co-operation of spiral ligament cells and AGAG produced by them. Thus we have tentatively concluded both that kanamycin is excreted via the above mentioned "excretion system" in the lateral wall of the membranous cochlea and that it damages this system to form the circulus vitiosus of its opopoxicity.


Gentamicin-induced mitochondrial damage in inner ear sensory cells of the lizard Calotes versicolor. Earlier morphological and histochemical studies on the effects on inner ear sensory cells caused by aminoglycoside antibiotics have failed to give sufficient information of the genesis of these effects. The present study was focused on the phases of progessive mitochondrial changes in sensory cells of the the lizard basilar papilla induced by consecutive large doses of gentamicin. The mitochondria react by swelling, changes in the configuration and number of the cristae and formation of matrical inclusions. Myelin figures are a consistent finding in degenerating cells after gentamicin exposure. These are shown to be derived from changed mitochondria. The final product is an "onion-like" structure which is built of primitive membranes. There is a marked difference in reaction to the damage between individual mitochondria in the same cell. This difference is also evident between individual sensory cells in the same specimen. By studying the phases of the mitochondrial breakdown process in the sensory cell, some additional information on the changes in cell metabolism caused by ototoxic drugs, may be extracted.


Breast feeding and biological development. The superiority of human milk as compared with milk of other origin for the feeding of newborns, term or preterm, can be analysed in terms of biological development related to digestive, metabolic and excretory functions during foetal and postnatal life. The macro- and micro-anatomical developments of the intestine are complete in the 6th foetal month. The brush border and some of its enzymes (saccharase-isomaltase) exist already from the 6th foetal week, whereas other enzymes (lactase and intracellular transport enzymes) appear much later. The major gastric and pancreatic enzymes, as well as the synthesis of biliary acids, do not reach maturity until after birth. Several metabolic functions, e.g. the synthesis of cystine from methionine, of tyrosine from phenylalanine, and of urea from ammonia, are still limited at the time of birth. The capacity for excretion of sodium, the osmotic urinary load, and hydrogen ions is suboptimal, especially in the prematurely born. All these circumstances imply that human milk, with its protective properties, represents optimal adaptation to the needs of the child in the perinatal period.


Comments on the acoustic-reflex response for bone-conducted signals. Previous studies which have measured acoustic-reflex responses to bone-conducted signals have not effectively differentiated reflex responses from artifacts. A convenient method for identifying such artifacts was developed and employed on some acoustic-reflex measures for bone-conducted signals. The findings indicated that artifacts result when a frequently-used acoustic admittance meter (Grason-Stadler 1720B) and a conventional bone vibrator were used to measure reflex responses for tonal and noise-activating signals. It was suggested that the method be employed in future studies which investigate the acoustic reflex in response to bone-conducted signals.


WHO collaborative study on breast feeding. WHO, concerned with the declining breast feeding rate in developing countries, has organized investigations in nine different countries of different aspects of breast feeding and breast milk with the ultimate aim of formulating programmes of intervention. The basic epidemiological study on 24000 mother/child pairs is just completed and some preliminary data are reported on the pattern of breast feeding in the three studied socio-economic groups--urban elite, urban poor and traditional rural--which differ significantly in their breast feeding rate as well as in the pattern of return of menstruation in breast-feeding and non-breast-feeding mothers.


New knowledge in human milk immunoglobulin. One of the anti-infection principles of maternal milk is the predominant milk immunoglobulin, secretory IgA. This immunoglobulin contains antibodies against many pathogens and potential pathogens, viruses as well as bacteria, including several members of Enterobacteriacae. The antigenic stimuli for these milk antibodies seem to take place in the Peyer's patches of the intestine. Lymphoid cells leaving the patches after antigenic exposure seem to home to the mammary glands via the lymph and blood circulation. As a result, the milk contains secretory IgA antibodies against, among other things, the intestinal bacteria of the mother. These milk antibodies might reflect the spectrum of bacteria and viruses in the community and may be important for the protection of the breast-fed baby. Via the same homing mechanism the maternal milk obtains antibodies against dietary antigens, including cow's milk proteins. Studies of infants on mixed feeding suggest that the secretory IgA antibodies against the bovine proteins diminish the antigenic exposure, indicating the possibility of an anti-allergic mechanism.


The volume of trapped gas: a new and sensitive test for the detection of exercise-induced bronchospasm in children. The volume of trapped gas (VTG) was measured at the end of a nitrogen multiple breath wash out procedure in 16 asthmatic and 10 healthy children before and after exercise. When compared to conventional spirometric variables VTG was the most sensitive test for detection of exercise-induced asthma (EIA). The VTG was significantly higher before exercise in the asthmatic children and increased significantly after exercise, while it did not change in the healthy controls. The significance of changes caused by EIA increased if VTG/TLC % or VTG/VC % wer used. Salbutamol inhalation normalized the VTG in all the asthmatic children.


Tissue levels of kanamycin in correlation with oto- and nephrotoxicity. The time courses of kanamycin (KM) levels in the perilymph, kidney, liver, brain and blood were observed by a bioassay method in normal guinea pigs and in animals pretreated with KM for 10 successive days. In the kidney and perilymph of the normal guinea pigs, the injected KM became highly concentrated and was eliminated only after a protracted delay. This tendency was much more intensified in kidney and perilymph of the pretreated animals. By contrast, the KM in blood and brain was eliminated rapidly both in the normal and in the pretreated animals. It is concluded that the high accumulation and slow elimination of KM by the inner ear and kidney and, moreover, the enhancement of these phenomena by successive pretreatment are one of the important factors in the origin of oto- and nephrotoxicity.


Congenital defects in a cohort followed for seven years. A geographically limited cohort of Finnish children was followed from birth for seven years, and all congenital abnormalities were recorded and classified and special attention was given to the cumulative detection rate, and the time of detection of various defects. Of 3674 pregnancies 135 babies with or without defects were stillborn or died during the neonatal period. The remaining 3539 were followed up to seven years, when the percentage follow-up was 81.7%. Detailed information on 76 malformed livebirths registered in the neonatal period was available in 63 cases (82.9%). The diagnosis was found to be incorrect in 6 cases and additional defects were registered in 7 of these children. Additional congenital abnormalities detected in the follow-up study were divided into three groups: all congenital disorders or abnormalities with prenatal etiology (248 children), all congenital defects (111 of these 248) and structural malformations (31 of these 111). The cumulative detection rates in these groups increased with time and at the end of the study when the children were aged seven were 9.4%, 5.6% and 2.6%, respectively.


Organ culture of the 16th gestation day mouse labyrinth. A model suggestion for pre- and post-partum development. The 16th day mouse embryo inner ear was explanted and cultured "in vitro" for 6 days, which corresponds to 1 day post-partum development "in vivo". A normal development occurred both when the inner ear anlage was divided into a vestibular and a cochlear portion and when it was cultured as a whole. The present model system may provide a helpful tool in the study of both normal development and inner ear pathology.


Increased intracranial pressure in cystic fibrosis. Three cystic fibrosis infants with severe respiratory distress had increased intracranial pressure (with bulging fontanels) which cleared parri passu with improvement in the chest condition. It is proposed that the intracranial hypertension is a result of raised venous pressure, itself secondary to the intrathoracic obstruction to venous return, consequent on the bronchial obstructive disease.


Sonotubometry. An acoustical method for objective measurement of auditory tubal opening. The sound conduction method for measurement of the Eustachian tube opening has been studied and modifications made in the test procedure to increase its easy performance and reliability. By holding the sound source near to the nostril, mounting the microphone into a circumaural ear defender and by feeding the output of the microphone through a filter with a very narrow bandwidth (3.16 Hz) many of the pitfalls of the sound conduction technique described earlier could be removed. Recording of the transfer function between the nasal tip and external auditory meatus and recording of the spectrum of swallowing sound revealed that the useful frequency rang for the measurements was upwards from 5--6 kHz. By using the three frequencies 6, 7 and 8 kHz the method showed tubal opening in 90 or 95% of normal ears depending on whether the minimum amplitude accetped was greater than or equal to 5 or 1--4 dB, respectively.


Renal functional adaptation in the remnant kidney in patients with renal agenesis and in patients nephrectomized in childhood. The renal response to volume expansion was determined in four patients with renal hypertrophy due to unilateral renal agenesis (URA) and in four patients with renal hypertrophy due to nephrectomy (Nz). Four healthy controls were also studied. The studies were performed during water diuresis and following i.v. infusion of isotonic saline solution. Conventional clearance techniques were used. GFR and PAH clearence were increased to about the same extent in Nz and in URA. Fractional Na+ excretion was highest in the Nz group and lowest in the control group. It was higher in the Nz group than in the URA group. Fractional water excretion (V/GFR) and free water clearance (CH2O) were also determined and the results indicate that the high fractional excretion of Na+ from the hypertrophied kidney can be attributed to reduced fractional reabsorption of filtrated Na+ both in the proximal and the distal tubules. The fractional Na+ reabsorption in the distal tubule appears to be higher in URA than in Nz. It is concluded that glomerular tubular balance for Na+ is more similar to that found in healthy controls if the stimulus to hypertrophy occurs prenatally than if it occurs postnatally.


A computer-controlled binaural balance test. The commonly used ABLB procedure (Alternate Binaural Loudness Balance) is strongly influenced by two psychological factors: the consistency of the referred side and the increase in intensity in equal stages on this side. To avoid this influence, side and intensity have to be randomized. The test has therefore been subjected to computer control and the results are continuously checked as to their significance. 26 patients with suspected inner-ear disturbance showed a significant relative recruitment; by contrast, in not one of 14 normal-hearing persons was the result positive. This test takes no longer than the conventional procedure.


Relationship of maternal smoking to morbidity and mortality of the child up to the age of five. The effect of maternal smoking during pregnancy on the morbidity and mortality of the child up to the age of five was studied in 12068 births. The children of the smokers were compared with those of controls of similar age, parity, marital status and place of residence. Perinatal mortality was no higher among the smokers, but postneonatal mortality from 28 days to 5 years was almost significantly (p less than 0.05) higher. The children of the smokers were highly significantly (p less than 0.001) more often hospitalized in pediatric departments, the difference being clearest below the age of one. The average duration of hospital admissions was longer among the children of the smokers, and similarly the numbers of visits to the doctor and hospital admissions to any hospital under the age of one were more frequent among the children of the smokers. Respiratory diseases caused highly significantly more hospitalizations among these children.


Oesophageal varices as a late complication to neonatal umbilical vein catheterization. Three recent cases are presented. Haematemesis in children with splenomegalia and a history of neonatal umbilical vein catheterization should involve careful examination for oesophageal varices due to portal hypertension.


Effect of maternal anaemia on the placenta and the newborn infant. Foetal birthweight, placental morphometry and maternal, cord blood and placental haemoglobin and iron levels were studied in 69 anaemic mothers (haemoglobin less than 110 g/l) and 16 mothers without anaemia (haemoglobin greater than or equal to 110 g/l). The birthweight, placental weight and number of placental cotyledons were significantly reduced in the severely anaemic mothers (haemoglobin less than or equal to 60 g/l) and had direct relationships with the maternal haemoglobin levels. However, placental volume and surface area showed no constant relation to maternal haemoglobin. The haemoglobin and iron levels in the cord blood and placental tissue were found to have linear correlations with the maternal haemoglobin levels. The low levels of placental and cord serum iron in the severely anaemic mothers suggest that iron supply to the placenta and the foetus is affected in maternal anaemia and the foetus takes iron in direct proportion to the levels available in the mother.


Relationship between haemoglobin and serum testosterone in normal children and adolescents and in boys with delayed puberty. The concentrations of haemoglobin  and of serum testosterone were measured in 215 normal children and adolescents aged 7--20 years, and in 8 boys with constitutional delayed puberty. From the age of 14 years onward haemoglobin and testosterone rose in normal boys and differed significantly from the stable levels observed in prepubertal children and pubertal girls. In the entire series of normal boys (n = 118, age 7--20 years) concentrations of haemoglobin and testosterone were found to be closely correlated (r = 0.73, p less than 0.001). These results provide further evidence for a major role of testosterone in the control of erythropoiesis. Therefore, this correlation suggests the use of serum testosterone determination for the proper selection of haemoglobin reference ranges in boys. The respective reference ranges of haemoglobin corresponding to testosterone levels at 0 and 30 nmol/l were 120.5--148.5 and 143.5--171.5 g/l (95% confidence limits). Boys with delayed puberty were found to have significantly reduced median values of haemoglobin and testosterone for their chronological age, and 6 of the 8 boys investigated were truly anaemic on this background. Nevertheless, their haemoglobin concentration did appear appropriate as judged from their testosterone levels. This observation supports the idea that the selection of the relevant reference range for haemoglobin in boys should depend on the state of physical development as expressed by serum testosterone.


Disseminated Herpes simplex virus infection in ataxia-telangiectasia. The clinical and pathological features are described in a child with ataxia-telangiectasia, complicated by fatal disseminated herpes simplex virus infection. Herpes simplex virus was isolated from the patient's blood, and the histopathological findings in the skin, liver and adrenals were consistent with herpes simplex virus infection. The patient had a combined immune deficiency state, as a part of the ataxia-telangiectasia syndrome. She had imparied cellular immune response to herpes simplex virus and developed no antibodies against the virus. To our knowledge, this is the first fatal case of disseminated herpes simplex virus infection in ataxiatelangiectasia.


Scanning electron microscopy of neoplastic neurogenic rat cell lines in culture. The surface structure of a series of malignant neurogenic rat cell lines in culture has been investigated by scanning electron microscopy. Neoplastic transformation was induced by a single transplacental administration of the carcinogen ethylnitrosourea (ENU) to BD-IX rats on the 18th day of gestation. The malignant cell lines were established either by explantation into culture of cells from solid gliomas or neurinomas developed in the offspring, or by transfer of fetal brain cells to culture where they subsequently underwent malignant transformation. A high degree of surface activity was observed, as evidenced by microvilli, filopodia, ruffling membranes and zeiotic blebs. Surface activity was highest in cell cultures giving rise to glioma-like tumours upon re-implantation into syngeneic hosts, and low in those giving rise to neurinoma-like tumours, with one exception. The lowest surface activity was seen in a cell line which was not tumourigenic. High surface activity was mostly correlated with a high degree of aneuploidy. No correlation was apparent with other properties of the neoplastic cell lines, e.g., stem line ploidy and population doubling time in cell culture.


The myocardial capillary vasculature in repeated physical exercise. An experimental investigation in the rat. The neoformation of myocardial blood capillaries was investigated on cardiac autoradiograms from 3H-thymidine injected rats that had been swimming-exercised for two weeks, rats that had been resting for three months following the exercise, and rats in which the rest had been followed by a second two-weeks period of exercise. The initial period of exercise induced a signficant capillary neoformation in the hearts. The newly-formed vasculature was found of functional significance still at the end of the resting period and available for the increased demands on the myocardial vasculature when the exercise was resumed.


The effect of tobacco smoke condensate on the growth and longevity of human diploid fibroblasts. Human embryonic diploid lung fibroblasts were exposed to various fractions of cigarette smoke condensate over their in vitro life-time. Most fractions were toxic at a concentration of 50 microgram/ml, with the exception of the strong acid and one water soluble basic fraction, which stimulated growth and increased longevity significantly at this concentration. Most fractions produced no effect on cell growth at 10 microgram/ml, with the exception of another basic fraction which inhibited growth at 1 microgram/ml. Nicotine had no apparent effect on growth and longevity at 50 microgram/ml. The neutral fraction containing the polynuclear hydrocarbon carcinogens produced normal growth and longevity at 10 microgram/ml. No cell transformations were observed.


Studies on the rat liver following iron overload. 1. Fine structural appearance. Iron overload of the rat liver following parenteral administration of Jectofer (an iron sorbitol citric acid complex) was studied in the electron microscope. Abundant ferritin-like granules were present in parenchymal and Kupffer cells, partly free in the cell sap and partly concentrated in 3 types of membrane-bound organelles, with characteristic appearances. In the parenchymal cells these organelles consisted of lysosome-like structures, apparent autophagic vacuoles, and vacuoles lacking features linking them to specific cytoplasmic elements. Organelle-bound ferritinlike granules in the Kupffer cells were demonstrated in lysosomelike structures, in phagocytic vacuoles, and in tubular and vacuolar elements referred to as "type 1" and "type 2" bodies. No ferritin-like granules were observed in other cell types than parenchymal and Kupffer cells.


Absence of association between oestrogen-receptor content and in vitro oestrogen sensitivity in human breast cancer. Breast-cancer tissue from 25 consecutive patients was investigated for oestrogen receptor content and for oestrogen-induced changes in tritiated thymidine uptake by explanted cells. A higher oestrogen receptor content was not associated with any statistically significant increase in oestrogen sensitivity. Neither the dissociation constant (Kd values), nor the oestrogen binding capacity (f mol oestrogen bound/mg supernatant protein) was found to be associated with in vitro oestrogen sensitivity. One receptor-negative tumour showed oestrogen sensitivity in vitro.


Incidence of salivary gland neoplasms in Greenland with special reference to an anaplastic carcinoma. Forty-two salivary gland neoplasms were diagnosed in Greenland 1955--1974. Twenty-five cases were malignant of which 92 per cent were an undifferentiated carcinoma, histologically identical to malignant lymphoepithelial lesion. Age adjusted incidence rates for salivary gland carcinomas 1965--1974 were among the highest on record, significantly higher than in Denmark. Prognosis was poor with a 5-year determinate survival rate of 14 per cent. The majority of previously reported malignant lymphoepithelial lesions of salivary glands have occurred in Arctic dwellers in Alaska and Northern Canda. Virus infection and/or dietary deficiencies may be etiological factors. In the present study secondary nasopharyngeal carcinoma could not always be excluded.


Lithium-induced focal interstitial fibrosis in the rat kidney. An early stage of focal cortical interstitial fibrosis and nephronic atrophy was found by light microscopy in the kidneys of nine out of twelve rats which had received lithium for 9 weeks. The animals had excessive polyuria and increased requirement for sodium. The histological changes were in their distribution and the morphological structure similar to the lesions recently found in renal biopsy specimens from patients on long-term lithium treatment.


Acute hypertensive damage of arterial vessels of the heart. Experimentally-induced acute angiotensin hypertension has been shown to increase the permeability of cardial arteries and arterioles to plasma components within a few hours. Only in one of the coronary arteries was an increased and focal permeability for plasma components demonstrated, the penetration taking place into the entire thickness of the vessel wall. However, the permeability observed in intramyocardial small arteries and arterioles showed a distinct deposition of plasma components, both in the tunica intima and the tunica media and usually in the entire circumference of the vessels. The results support the view that an increased arterial permeability of the myocardial vessels for plasma components is an important initial stage in the development of hypertensive vascular disease of the heart.


Biliary hamartomas (von Meyenburg complexes) in liver needle biopsies. 2000 consecutive liver needle biopsies were examined for the occurrence of biliary hamartomas (von Meyenburg complexes, microhamartomas). In 12 biopsies (corresponding to 0.6 per cent) a total of 15 hamartomas were found as 2 biopsies contained 2 and 3 hamartomas, respectively. The incidence, morphology, location and differential diagnosis are discussed. In serial sections a communication between all the lumina in each hamartoma was found. In no case the diagnosis of biliary adenoma, congenital hepatic fibrosis or polycystic liver could be made. The hamartomas are of no clinical importance.


Bacterial contamination of heat-sterilized, heat-disinfected and chemically-disinfected haemodialysis monitors. The bacterial contamination of one heat-sterilized, three heat-disinfected and four chemically-disinfected monitor types was evaluated before and after dialysis. All monitor types were contaminated. In the heat-treated monitors the level of contamination varied with the intensity of the heat treatment and the technical design. They were less contaminated than the chemically-disinfected recirculating single-pass monitors. The latter were contaminated to a marginal degree, irrespective of the quality of the water supply. Each monitor showed a characteristic microbial flora, indicating that recontamination occurred from the same persistent focus. Aquired antibiotic resistance characters were rare among the potential human pathogens isolated from the dialysate. The level of contamination during dialysis is determined by a complex of factors, including the mode of disinfection, the technical design of the dialysis equipment, the duration of the dialyses, and the flora of the dialysate.


Bacitracin production by the high-yielding mutant Bacillus licheniformis strain AL: stimulatory effect of L-leucine. The high-yielding mutant Bacillus licheniformis AL produced only small amounts of bacitracin in the chemically defined M2 medium. L-leucine markedly stimulated bacitracin production and restored the mutant strain to its place as a superior producer as compared to Bacillus licheniformis ATCC 10716. Leucine also stimulated the growth rate of the mutant. The stimulatory effect of leucine on bacitracin production is discussed in relation to control mechanisms and overproduction of antibiotics.


The role of cell wall carbohydrates in binding of microorganisms to mouse peritoneal exudate macrophages. The recognition by macrophages of unopsonized bacteria was studied, employing a binding assay, performed at 4 degrees C. Various Gram positive and Gram negative bacteria were shown to bind to glass-adherent mouse peritoneal exudate cells under these conditions, Str. pneumoniae being the only exception. The binding could be inhibited by pretreatment of the macrophage monolayers with various monosaccharides. The role of particular components of the bacterial cell wall in binding was examined further using different strains of K. aerogenes and S. typhimurium with a known cell wall composition and mutant strains deficient in certain sugars. The ability of a particular constituent to inhibit binding was found to correlate closely with its presence in the bacterial cell wall. It is concluded, that this form of binding, mediated by cell wall carbohydrates represents a primitive recognition mechanism enabling phagocytes to bind microorganisms.


Deoxyribonucleic acid hybridization between different species of mycobacteria. The homology percentages between DNA from M. smegmatis ATCC 607 and DNA from nine various species of mycobacteria have been determined. DNA-DNA hybridization was measured in a spectrophotometer. The technique, calculation of results and the uncertainty of the method are described.


The importance of C5 and the role of the alternative complement pathway in leukocyte chemotaxis induced in vivo and in vitro by Bacteroides fragilis lipopolysaccharide. Chambers implanted subcutaneously in C5 normal (C5 N) and C5 deficient (C5 D) mice were used to examine the migration of polymorphonuclear leukocytes (PMNs) into the wound chamber fluid in response to injected Bacteroides fragilis lipopolysaccharide (LPS). The difference in PMN migration was highly significant between the two mouse strains, the C5 D mice showing no initial, but a low, delayed migration. The results from the study indicated that chemotaxis plays a major role in the accumulation of PMNs in the acute inflammatory response. Intraperitoneal endotoxin stimulation also showed a significantly lower total number of leukocytes in the exudate from C5 D mice as well as a delayed migration of cells compared to C5 N mice. No leukotactic mediators were elaborated in C5 D serum or exudate upon incubation with LPS when tested in a modified Boyden chamber. However, endotoxin-induced wound chamber fluid in C5 D mice showed an increasing leukotactic activity at the same time as the acute inflammatory response subsided in C5 N mice. Incubation of B. fragilis LPS in C4 deficient (C4 D) guinea pig serum indicated that the LPS was able to activate complement components to generated split products chemotacic for rabbit PMNs via the alternative complement pathway.


Rapid oncogenesis in vivo by chicken retrovirus OK10. The OK10 virus complex is known to contain two detectable viruses: a) focue-forming virus OK10V that transforms chick embryo cells, and b) an associated virus OK10AV present in excess that converts the morphology of cultured chick embryo cells. The pathogenesis of OK10 virus infection was studied, using 2--4 day old Brown Leghorn chickens. A group of chickens was sacrificed at weekly intervals, serum samples were taken and tissues were examined for virus. Autopsies of the chicken were performed and gross and microscopic changes were registered. After intraperitoneal injection of 10(4) focus-forming units of OK10 virus, infectious OK10AV was detected after one week in Bursa Fabricius, thymus and liver, and OK10V after two weeks in Bursa Fabricius but in no other organ. Neutralizing serum antibodies developed within three weeks. The first malignant changes, in the mesentery, were detected after three weeks. The infection was lethal in all experiments within 6--8 weeks. In the mesentery, the tumors consisted of large tumour cells with clear cytoplasm, a large nucleus and prominent nucleoli. The origin of these cells could not be established. The cells were surrounded by lymphoid cells. From the tumours, vontinuous cell lines were established which produced both viruses OK10V and OK10AV and had blast-like morphology. After intravenous injection of OK10 virus, tumours could also be found in liver, kidneys and testes. The associated virus OK10AV was injectious for chickens and induced neutralizing serum antibodies. One out of seven chickens died of leukosis after 1 1/2 years. The OK10 virus complex, consisting of a tumour-forming and a weakly oncogenic associated virus, appears to have a multiple oncogenic potential in its rapid oncogenic action in vivo.


Experimental endocarditis in rabbits. I. Technique and spontaneous course of non-bacterial thrombotic endocarditis. Insertion of a polyethylene catheter into the heart was used for regular establishment of sterile endocarditis in 52 rabbits. The catheter was inserted with the aid of guide wire, and distance marking on the catheter was used to obtain precise positioning, so that the catheter was retained with the curved distal end inside the left ventricle of the heart. The results showed that the catheterization procedure could be carried out with a high degree of accuracy. Uniform localization of the vegetations was obtained, these reaching a suitable size of development in all rabbits after insertion of the catheter for 3 days. Histological examination of the sterile vegetation showed that catheter withdrawal at this time would still permit the regular development of an infection. After withdrawal of the catheter, the sterile vegetations rapidly decreased in size and disappeared almost completely by 10 days. Sterile endocarditis in rabbits induced by a catheter for a period of 3 days proved to be a harmless and self-limiting disease. The model presented seems to be suitable for futher investigations on experimental bacterial endocarditis.


The presence in faecal extracts of bacterial cell wall components resembling viral structures. Electron microscopy of faecal extracts frequently shows organized structures which have a superficial resemblance to viral material in that it is more heterogenous and consists mainly of vesicles and tubules covered by subunits arranged in different patterns. Evidence is presented that this kind of material is derived from detached outer layers of bacterial cell walls.


Toxicity studies with human leukocyte interferon in newborn rabbits. Daily subcutaneous injections of 5 to 10 million units of partially purified human leukocyte interferon were given to newborn rabbits for 2 weeks or 1 month. The control groups received mock interferon, saline or nothing. The interferon treatment had no overt effect on the development of the animals during the period of treatment. The rabbits treated with interferon had leukocytosis, splenomegaly and prolonged postnatal extramedullary hematopoiesis in the liver and spleen. Certain immune responses were also demonstrated in the rabbits treated with interferon and mock interferon preparations. Platelet counts and the serum-ASAT, -ALAT, -LD and alkaline phosphatase values were normal.


Leukocyte chemotactic activity in cultures of unstimulated human lymphocytes. We have shown earlier that unstimulated human lymphocytes in in vitro cultures produce migration inhibitory factor into the supernatant. The evidence of spontaneous lymphokine synthesis is strengthened further by this study, which demonstrates leukocyte chemotactic activity in these culture supernatants. The factor has a molecular weight of more than 5000 daltons, it resisted heating for 15 min at 100 degrees C, and showed maximum activity at dilution 1:4-1:8 of the supernatants.


The role of C1s, C1r and properdin in the initiation of the C3b-dependent feedback mechanism of the complement system. The influence of activated C1s, C1r and properdin in the fluid phase initiation of the C3b-dependent feedback mechanism of the human complement was studied. It was found that C1s caused conversion of C3 and factor B in a normal serum, but not in a serum genetically deficient in C4 or in a serum to which Na2EDTA had been added. When a normal serum was incubated with C1r before incubation with C1s, only C3 was converted, whereas factor B remained in the unaltered native state. Properdin did not influence the C1s mediated conversion of C3 and factor B. When activated properdin was added to a properdin-depleted serum, both C3 and factor B were converted. Activated properdin was also incubated with purified C3 and purified C3b. It was shown that C3 was converted to C3b, but C3b was not degraded despite prolonged incubation.