Myocardial metabolism and performance during sodium salicylate infusion in dogs. The effect of sodium salicylate on net myocardial free fatty acid (FFA) uptake, myocardial oxygen consumption (MVO2), and the mechanical activity of the heart was studied in eight intact, anesthetized dogs. Sodium salicylate was given intravenously under basal conditions and during isoproterenol-stimulated lipolysis. Under basal conditions, sodium salicylate significantly reduced arterial FFA concentration, but did not influence net myocardial uptake of FFA, and MVO2 was unchanged. During isoproterenol infusion sodium salicylate reduced arterial FFA concentration 28% (P less than 0.01) and significantly reduced net myocardial uptake of FFA from 44.5 +/- 9.0 (mean +/- S.E.M.) to 22.3 +/- 2.1 mumol/min-100g tissue (P less than 0.05) and MVO2 from 20.3 +/- 2.2 to 160 +/- 1.9 ml/min-100g tissue (P less than 0.05). The reduction in MVO2 could not be explained by reduced mechanical activity of the heart. Most probably the mechanism for the reduction in MVO2 effected by sodium salicylate during isoproterenol infusion was mediated by reduced myocardial FFA consumption.


The influence of acetylsalicylic acid (aspirin) on gastric mucosal content of energy-rich phosphate bond. The mucosal content of adenosine triphosphate, adenosine diphosphate and adenosine monophosphate in mini-pig corpus gland area and in pyloric gland area was examined after aspirin ingestion in acute experiments and after ingestion for several weeks. Ingestion of aspirin led to a statistically significant decrease of adenine nucleotide content in corpus gland and in pyloric gland area. An inverse correlation between the pH of the aspirin suspensions and the size of the decrease was established in the short-time experiments. In non-affected pyloric gland area mucosa and adenine nucleotide content was significantly lower than in the corpus gland area. Pyloric mucosa was more susceptible to aspirin-induced lowering of adenine nucleotide content than was the corpus mucosa. Prolonged aspirin ingestion led to statistically significant reductions of adenine nucleotide pool. The findings explain the decrease in mucous secretion and in acid secretion demonstrated in several studies. The finding of lower and more susceptible adenine nucleotide pool in the pyloric area might be the explanation for the preponderant occurrence of aspirin ulcerations in this region.


Effects of different doses of acetylsalicylic acid on renal function in the dog. This study was carried out in order to examine the effect of increasing doses of intravenously administered lysine-acetylsalicylic acid (ASA) on renal function in dogs. The first purpose was to examine the acute effects on renal water and solute output. The second purpose was to correlate the para-aminohippuric (PAH) clearance measurements with measurement of renal PAH extraction and renal blood flow (RBF). After 7 mg/kg ASA (20-80 microgram SA/ml plasma) a decrease in sodium excretion was observed in all dogs. With increasing ASA doses, the urine sodium excretion declined to 23% of the control period excretion. Tubular reabsorption of free water increased 10%. A significant and dose-related decrease in PAH clearance was observed in all dogs, from 108.7 ml/kg ASA to 58.8 ml/min after 200 mg/kg ASA. The creatine clearance was unchanged. PAH extraction fell in all dogs, RBF (measured by flowmeter decreased 21% at the highest plasma SA levels, as compared with 46% decrease in PAH clearance. ASA seems to inhibit tubular transport of PAH. Inhibition of prostaglandin synthesis by ASA offers one explanation of the effects of RBF and sodium excretion.


Effects of different doses of chlorpromazine on renal function in the dog. This study was carried out to examine the effects of low 'alpha-blocking' and higher 'membrane-stabilizing' doses of chlorpromazine (CPZ) on renal function. CPZ was given at slow infusion rate either intravenously or into the left renal artery at three levels (0.5-1.0, 3-8, and 10-15 mg/kg) to 10 anesthetized dogs. An increase in plasma hemoglobin sometimes occurred within few minutes after infusion of more than 10 mg/kg CPZ, probably due to a hemolytic effect of such high doses. Systemic infusion of 0.5-1 mg/kg CPZ caused an increase in urine volume, sodium excretion, and renal plasma flow, and a decrease in filtration fraction and free water clearance was demonstrated in all dogs. At higher CPZ doses renal plasma flow increased further, whereas urine volume and electrolyte excretion were of the same order at all dose levels. A 21% decrease in tubular maximum para-aminohippurate transport (Tm(PAH)) was observed at the highest CPZ doses. After unilateral renal intra-arterial CPZ infusion the percentage change in urine volume, urinary sodium excretion, and Tm(PAH) were of the same order on the infused side as on the contralateral side. Even though the results at all dose levels can be explained by an 'alpha-blocking' effect of CPZ, possible membrane-stabilizine effects of CPZ cannot be excluded.


Effects of androgens on oxygen affinity in vivo and 2,3-diphosphoglycerate content of red cells in peripheral arterial insufficiency. The effect of testosterone on the red cell concentration of 2,3-diphosphoglycerate (2,3-DPG) and on the in vivo oxygen affinity of venous blood was investigated. Six male patients with peripheral arteriosclerosis received 500 mg testosterone enantas intramuscularly for 15 weeks. Six matched controls received 2 ml NaCl weekly for the same period of time. The hemoglobin concentration, the hematocrit, and the 2,3-DPG concentration increased significantly during testosterone treatment, while no significant changes in the oxygen affinity could be detected. It is concluded that testosterone in the doses applied here does not improve oxygen unloading from the blood.


Differences between capillary and venous blood glucose during oral glucose tolerance tests. The simultaneous capillary and venous blood glucose concentrations were measured during 36 oral glucose tolerance tests performed in 36 postmenopausal women. Three of the subjects had chemical diabetes mellitus. In samples obtained before and 120-180 min after the glucose load the differences between capillary and venous blood glucose concentrations were low, whereas samples taken after 15-90 min showed a mean capillary-venous difference of 1.8 mmol/l. This is higher than previously stated by the World Health Organization and the British Diabetes Association. If the definitions that were recommended by these two bodies are used for defining whether the result of an oral glucose tolerance test is to be considered 'normal' or 'abnormal', the present results indicate that the verdict will in some cases be influenced by the route by which the blood was obtained.


Radioimmunological determination and characterization of cathodal trypsin-like immunoreactivity in normal human plasma. A radioimmunological method for determination of human cathodal trypsin-like immunoreactivity is described. DFP-treated human cathodal trypsin is used as standard and tracer. Freshly drawn normal human plasma contains about 25 microgram/l of cathodal trypsin-like immunoreactivity measured as DFP-treated cathodal trypsin. The normally circulating cathodal trypsin-like immunoreactivity is shown to consist mainly of cathodal trypsinogen.


Determination of bradykinin in blood by a sensitive radioimmunoassay. Antibodies of high avidity (maximum Km 1.3 X 10(10) L/M) were produced in rabbits against bradykinin coupled to ovalbumin with toluene 2,4-disocyanate. Tyrosin8- bradykinin was labelled to a specific activity of 530-700 Ci/mmol with 125I by means of lactoperoxidase. Sensitivity of the radioimmunoassay was 0.01 microgram/l blood. Specificity studies demonstrated the essential role of the C-terminal arginine of bradykinin for binding to antibody. Mean recovery of [3H]bradykinin internal standard after the preparation of 86 blood samples was 39.0%. The major loss occurred during ethanol precipitation. In venous blood collected at random conditions from 32 normal subjects the bradykinin concentration ranged 0.04-0.46 microgram/l and showed no sex difference.


Radioimmunoassay of vasopressin in unextracted plasma. A radioimmunoassay (RIA) for arg8-vasopressin (AVP) in unextracted human plasma was based on a sensitive anti-AVP rabbit antiserum, inhibition of enzymatic damage to [125I]AVP and AVP, and the use of an individual plasma blank, to correct for interference of plasma factors with the RIA. Sensitivity was 0.4 pg of synthetic AVP detected, corresponding to 1.2 pg/ml of AVP in human plasma. Recovery of AVP added to pooled plasma was 94 +/- 9.3% (mean +/- S.D.) in the low range (AVP, 2.8 pg/ml added) and 106 +/- 11.7% in the high range (45.0 pg/ml added). In 26 healthy, ambulatory subjects on ad lib, water intake, plasma AVP concentration was 2.0 +/- 1.22 pg/ml in the supine position and in 28 healthy subjects, 6.2 +/- 4.3 pg/ml in the upright position. Water loading suppressed the plasma AVP concentration. Smoking caused increased plasma AVP in 3 subjects despite water loading.


Evaluation of the sampling technique and storage of blood using the B 109 Arterial Blood Sampler syringe. To evaluate the B 109 Arterial Blood Sampler (Radiometer), 10 different samples were analyzed for Pco2, Po2, and pH. The aerobic sampling technique, followed by storage for 2 h in water at 1 degrees C, induced small, but clinically insignificant, changes in the measured values.


Relation between corpus allatum and haemolymph proteins in Sphaerodema rusticum Fabr. The active and inactive stages of the corpora allata have been described on the basis of size and nucleo-cytoplasmic ratio. The polyacrylamide gel disc electrophoresis of the haemolymph has been done in the males and different stages of reproducing females. A protein fraction with a value 14 less than or equal to Rm less than 16 has been observed only in females. Out of 8 protein fractions, 5 showed oscillations in their concentration at the time of vitellogenesis. Finally active stages in the corpora allata are correlated with the fluctuations in haemolymph protein concentration.


The role of hypertrophic cartilage in endochondral ossification. Normal stages of histogenesis of long bones show that the hypertrophy of cartilage cells is the pre-requisite for the perichondrium to take up osteoblastic activity, (Fell 1925, Lutfi 1971). Cooper (1965) found the cartilage cells from epihysis of the long bones of chick failed to induce chondrogenesis in somites in mice and chick whereas flat cells and early Peripheral cells could do same. Fell and Landauer (1935) noticed that in avian phocomelia the hypertrophied cartilage cells fail to hypertrophy leading subsequently to deformities of long bones. Presently an attempt is made to analyse this process further by culture experiments. It is found that complete tibial rudiment or part of it grows normally in vitro with good differentiation of various zones and the development of osteoid tissue. However it is noticed that when cartilage and the associated perichondrial tissues are grown separately, there is no patterned growth of cartilage and the absence of development of osteoid tissue in either types of cultures. The role of perichondrium and cartilage is discussed in the light of experimental findings.


The behaviour of the donor melanoblasts in the non-pigmented host embryos. The behaviour of the donor melanoblasts from the leg bud mesoderm of Silver Campine implanted into White Leghorn embryos has been studied. Their schedule of migration from intracoelomic grafts to various parts of hosts is worked out. Different hypotheses for differentiation of grafted spherical melanoblasts in various tissues of hosts have been investigated.


Effect of luteinizing hormone on female Puntius ticto (Ham.). Low doses (0.2 mg and 0.4 mg) of LH did not reveal any effect on the ovary of Puntius ticto (Ham.), but with 0.6 mg of LH the vitellogenesis began. Full maturation in the ovary was recorded with a total dose of 1.2 mg of LH and the fish spawned with a dose of 1.4 mg of LH.


Ventral exocrine gland of larva of Spodoptera (Prodenia) litura (Fabricius) (Lepidoptera: Noctuidae). The morphological and histological structure of the ventral exocrine gland of the larva of the tobacco caterpillar, Spodoptera (Prodenia) litura (Fab.) is shown. The proximal region of the gland is capable of protrusion through the prothoracic sternal slit as an elongate organ reaching upto the spinneret. The middle region of the gland shows characteristic giant cells in only one of the walls of the epithelium, while the distal region shows a thin flat epithelium with small round closely situated nuclei resting against the tunica propria. The gland probably secretes a gummy fluid for larval movements rather than a stinking odourous fluid for defense.


Relationship of blood vessels to small intensely fluorescent cells in the autonomic ganglion. In our experiments we observed the relationship of the blood vessels to the small, intensely fluorescent cells (SIF cells) in the lower mesenteric ganglion of the cat. We injected the solution of Evan's blue into the ganglia and processed them with the fluorescent histochemical method by Falck and Hillarp. We observed that the SIF cells are placed in the ganglia closely to the blood vessels or closely round them. When observing lager groups of SIF cells placed at the edge of the ganglia a dense network of the blood vessels was observed among these cells.


[Afferent nerve endings in the small intestine and the stomach. Light and electron microscopic studies]. 1. In the mucous membrane of the duodenum and pylorus there have been identified free club- and tree like endings by ligth and electron microscopy. These endings lie flat between the muscularis mucosae and the glandular basis. 2. In the duodenum of the dog the receptors are undoubtly formed by myelinated axons. 3. According to neurophysiological results these free afferent endings are similar to PAINTAL'S (1957, 1963) mucosal mechanoreceptors.


[Connective tissue in the perivascular spaces of subependymal capillaries of the spinal cord in the rabbit]. The normal structure of the subependymal capillaries and venules of the spinal cord was studied in rabbit. The endothelial cells of the capillaries and venules are surrounded by an irregularly formed perivascular space, about 0.5 to 3.3 micrometer wide, which is delimited by an endothelial and glial basal lamina. The space contains a framework of collagen fibers. A period-acid-bisulfit-aldehydthionine-method (Specht) permits to find the perivascular connective tissue lightmicroscopically, while they can be identified by electron microscopy. The significance of the perivascular connective tissue is open to discussion. Structural and functional problems have been reviewed in this context.


[Enzyme histochemical studies of the general body surface apocrine glands in the domestic cat]. With enzyme histochemical methods, the distribution and the activities of various oxidative and hydrolytic enzymes in the apocrine glands of the general body surface of the domestic cat were investigated. The results obtained support the view that these glands are clearly active in function. On the whole, however, the relatively weak enzyme activities in the secretory portion of the glands point to only unimportant secretion production rates.


Follicular and reticular arrangements of medullary cells in the adrenal gland of Göttingen Miniature pigs. In the adrenal gland of Göttingen miniature pigs adrenaline- and noradrenaline-storing cells showed follicular and reticular arrangements, which were not observed in the domesticated form (German land race) of Sus scrofa. Chromaffin cells could contain vacuoles, which were sometimes connected with follicles and filled with a material indistinguishable from that in follicles. Coated and smooth vesicles with contents of various electron densities were particularly abundant around vacuoles and Golgi areas, which were often found to be closely associated. Chromaffin cells were unconspicious with respect to other ultrastructural details. A comparison was made between this mode of arrangement and that seen after intense stimulation of the adrenal medulla using insulin, reserpine, or vinblastine. The possible significance of this particular pattern of arrangement of chromaffin cells is discussed.


Lysosomal disposal of secretory granules and their transformation into pigment particles in spontaneous prolactin cell adenomas of the rat pituitary. Light and electron microscopic study of spontaneous prolactin cell adenomas, found at autopsy of 26 aging female Long-Evans rats and of 9 aging male Wistar rats, revealed pigment particles in the cytoplasm of some adenoma cells. It is postulated that most of the pigment particles derive from secretory granules. The presence of crinophagy and autophagy are interpreted as the morphologic expressions of lysosomal activation. The causative mechanisms accounting for lysosomal disposal of secretory granules and their transformation to pigment particles remain to be elucidated.


Ultrastructural and cytochemical localization of calcium in a rat cardiac muscle in normal and experimental conditions. The experiment carried out by us on the, stimulated by adrenaline, cardiac muscle allowed the activation of calcium localized mainly in the mitochondria, MA and FA of the intercalated discs and SR to be translocated in the direction of the sarcomere myofilaments and this especially to the thin actin filaments. The authors' experimental proves, that during the contraction--relaxation function of the cardiac muscle there exists a circulation rythm or a oscillatory functional flow of calcium ions between the mitochondria, intercalated discs and SR and the contractile fibrillae of the sarcomere.


[The dorsomedial envelope in the human thalamus. A pigment architectonic study]. The shape and extension of the dorsomedial envelope (HASSLER 1959) in the human thalamus was examined in 800 micron thick slices stained with aldehyde-fuchsin. By means of selective staining of intracellular lipofuscin granules the pigment architecture of these grisea can be clearly depicted. The dorsomedial envelope consists of the nucleus cucullaris and the nucleus parataenialis. It covers the ventricular surface of the territorium mediale with an almost unbroken cellular layer stretching caudally as far as the nucleus pulvinaris superficialis. The strongly pigmented nucleus cucullaris can be seen as the main nucleus of this part of the envelope. It can be divided into three areas: nucleus cucullaris oralis, interpolaris, and caudalis.


[Spermatogenesis in the yellow-bellied toad (Bombina variegata variegata L.) during the seasonal activity period and in correlation with the mating call activity (Discoglossidae, Anura)]. The spermatogenic tissue in the yellow-bellied toad Bombina variegata has certain properties not shared by other Central European anurans. Sertoli cells are lacking; the sperms are not bundled within the seminiferous tubules, but rather they form and mature in a connective-tissue follicle that is cellular in nature. Spermatogenesis is not a continuous process, at either the spermatocyte or the spermatozoa formation stage. Rather, there are periods of stagnation and of proliferation, which can be correlated with the periods during which the male toads produce mating calls and with the pauses between the calling periods. The crucial participation of hormonal factors in these processes is discussed.


Studies on the seasonal histocytological changes in the internal and chromaffin cells of male Puntius sophore (Ham) in relation to its reproductive cycle. An attempt has been made to correlate the activities of interrenal and chromaffin cells with the reproductive cycle of Puntius sophore. Chromaffin cells do not have any significant bearing while interrenal cells undergo qualitative and quantitative changes which have been correlated with the various phases in the reproductive cycle of this fish. These cells undergo degranulation and vacuolisation during spawning phase, disorganisation during regression phase, and reorganisation and gradual growth during resting and prespawning phases. These cells thus appear to play an important role in the reproductive physiology of this fish.


Further observations on the B-type neurosecretory cells in the thoracic ganglion of the crab, Potamon magnum magnum (Pretzman). Only four types of the secretory neurones were observed in the thoracic ganglion of the fresh water crab, Potamon magnum magnum (Pretzman). These cells are classified as A, A', B and C types. Our results also confirmed that the B and B' types of cells (BAID et al. 1968) are one and the same type, the B cells. The B cells are of two forms, with and without the axons. They clearly showed sequential histological patterns pointing out to their phases. The secretory material is discharged either through the periphery or through the axon and periphery both. The vacuoles were observed in both the forms of the B cells. The remarkable sign of the activity of the nuclear membrane especially at the beginning of the secretory cycle and the appearance of the first secretory granules around the nucleus strongly support the vital role of the nucleus in the initiation of the secretory cycle.


Death-discordant twins--a new method to evaluate genetic factors in chronic diseases. One of the most important lines of research on unselected large scale twin registries are mortality followups. Death-specific concordance rates have been calculated using different measures of concordance. These estimates are of great importance but they only reflect an "all or-none" classification of the genetic effect. It is suggested that mortality studies could be extended to, and include studies on, death-discordant twins. Such studies combine the advantages from mortality follow-ups on total twin populations with the detailed clinical investigation on subsamples. By examining the surviving cotwins with respect to various traits and supposed risk factors, an opportunity has been provided to study the genetic determination on the development of disease. This approach has been used in a study of ischaemic heart disease (IHD) and its risk factors in a representative subsample from the Swedish Twin Registry.


Alcohol consumption in relation to factors associated with ischemic heart disease: a cotwin control study. Moderately alcohol-discordant male twin pairs, aged 45-65 years, have been examined with respect to ischemic heart disease (IHD) and associated factors. No conclusion can yet be drawn with regard to manifest or subclinical IHD, while significant disparities were found with regard to systolic and diastolic blood pressures, high cigarette consumption, hyperglycemia, and serum cholesterol; the greater number of findings of pathological values were found in the high alcohol-consumption as compared to the low alcohol-consumption cotwins. These findings offer a possible explanation for the increased number of reports showing a connection between high consumption of alcohol and occurrence heart disease.


Gene interaction in the phenotypic expression of mental diseases. A genealogical analysis is carried out on the pedigrees of 10 twin pairs with two or more psychoses. The probands' symptoms reveal some peculiar aspects, i.e., an atypical phenomenology possibly due to the interference of more pathological genes. Schizophrenia, depression, epilepsy, and obsessive neurosis, are found in the pedigrees in different combinations. The study of these pedigrees would lead to the conclusion that interaction of more than one psychosis gives rise to atypical forms as a result of an attempt to establish a state of balance between opposing dynamic actions, as in reversible chemical reactions. Probands' symptoms are less severe and with an often more favourable prognosis. Epilepsy tends to become independent and the major psychoses seem to be epistatic on it. As for obsessive-compulsive neurosis, probands may progress into schizophrenia or depression if one of these psychoses is present in the pedigree, or may represent the neurotic form of the major disease.


Twin pregnancy as a high risk pregnancy: new medical statistical data from the German Democratic Republic. In 1972 the rate of multiple births showed a much more substantial decrease than in the years before. In the period 1963-1971 it dropped from 20.3% to 19.3% and in 1972 to 18.3%. The frequency of low birth weight in children from a multiple birth is 10 times higher than in all newborn children and the early neonatal mortality of children from a multiple birth is 8 times higher than that of all newborn infants. Cerebral damage is 30 times higher in children of low birth weight than in children of normal birth weight. In the period 1965-1967 perinatal death associated with cerebral damage (recorded on the death certificate) accounted for 5.7% of all children of low birth weight and for 0.2% of children weighing at birth over 2500 g. Early diagnosis of multiple pregnancy and early in-patient care of women with multiple pregnancy will improve the development of multiple fetuses and give children from a multiple birth much better chances in life. In all twin studies it has to be considered that a relatively high proportion of twins is affected to a higher or lesser degree by cerebral damage.


A case of simultaneous interstitial bilateral pregnancy. Twin pregnancies may present tubal involvement in the following cases: (1) simultaneous intra- and extrauterine pregnancy; (2) interstitial bilateral pregnancy (either simultaneous or not); (3) multiple pregnancy in the same tube; and (4) simultaneous interstitial and ovarian pregnancy. Interstitial bilateral pregnancy appears to be by far the rarest kind of tubal twin pregnancy, apparently only one case having been reported in the literature, and this referring to a nonsimultaneous pregnancy. A case is now reported that therefore appears to represent the first observation of simultaneous interstitial bilateral pregnancy.


Hypothesis of an ovular regulation of pregnancy weight-gain. A retrospective study of 127 twin pregnancies has been carried out, considering the relation between maternal weight-gain and zygosity of the ovum. At 28 weeks of gestation, the maternal weight-gain distribution goes on according to a bimodal curve, the analysis of which shows that each pike corresponds to one twin-pregnancy variety. Whatever the considered term might be (28-32-36 weeks), the maternal weight-gain is higher in DZ than in MZ pregnancies, and it should be pointed out that toxemic pregnancies, in each group, have nothing to do with this difference. This maternal weight-gain difference may reflect the known quality difference between MZ and DZ ova. The data lead to set up the more general hypothesis of an ovular regulation factor of the maternal weight-gain, in addition to classic data such as the own fetal weight, its annexes, and maternal diet.


Leukemia in twins: antenatal and postnatal factors. Two factors emerged from a search for obstetric phenomena that might explain concordance of leukemia in both members of a twin pair within days or months of each other: antenatal exposure to ionizing radiation; and antenatal cojoined intrauterine circulation. In addition, antenatal tumor metastasis and chromosomal changes, antenatal or postnatal, may be contributory. Continued observation of reports should be carried out.


Frequency of thoracoomphalopagus conjoined twins in Thailand. Twenty-two cases of conjoined twins have been collected in Thailand. The numbers occurring in the various parts of Thailand are listed. No known cases have occurred between the years 1968-1973. The extent of union between the conjoined twins is described and illustrated. Some theories are offered as to etiological factors which might account for the occurrence of conjoined twins.


Morphological and cytogenetic studies on conjoined twins. Two cases of monoamniotic conjoined male twins, born at term after normal pregnancies, are reported. The first case, a bicephalus, shows hypoplastic and malformed left-side organs, absence of the left umbilical artery, and two communicating hearts, the left one with three cameras. The second case, a pygothoracopagus, consists in a twin "parasite", with no head but with two upper and two lower limbs, slightly less developed than those of the formed twin. The left eye of the formed twin is double than the right one and contains two eye apples -- one well-formed and the other rudimentary. There is a rudiment of a second mouth on the left cheek. The umbilical cord contains five blood vessels --- one umbilical vein and four umbilical arteries. The cytogenetic study of the pygothoracopagus reveals aneuploidy, more pronounced in the "parasite" than in the formed twin.


A case of conjoined twins.

A case of conjoined twins. Among 56,249 maternities in the Collaborative Perinatal Project, 615 were twin maternities. One of these resulted in stillborn thoracoomphalopagus MZ female twins with multiple cardiovascular, alimentary and other malformations. The case is of further interest in that the mother had a surgically removed brain tumor in childhood and exhibited neurological symptoms and bizarre behavior before and during pregnancy. Drugs and treatments which she received during pregnancy are not known to be teratogenic.


Monoamniotic twins.

Monoamniotic twins. Six new cases of monoamniotic twins are reported. All had true knots of the cord, the result being double survival in 5 cases and 11 normal children. The mechanism of twin development is described and monoamniotic twins are placed in accordance with the two theories from the literature. A short review of both the Scandinavian and the world cases is presented.


Delayed ovulation and monozygotic twinning. Aiming to show that delayed ovulation may induce MZ twinning, follicular maturation was induced in the rabbit by a small quantity of Pregnant Mare Serum Gonadotropin (16 UI four times): coitus, which induces ovulation in the rabbit, was delayed 60 hours after the last injection. From the 387 blastocysts obtained after this treatment, 6 (1.5%) were pairs of MZ twins, twinning being otherwise exceptional in the rabbit. Other anomalies were shown by the embryos, apparently related to a deficient quality of the eggs: high embryonic mortality (62% vs. 27% in controls) and chromosomal anomalies (20%) such as trisomies, triploidies, and chimaeras. The relation between MZ twinning, chromosomal anomalies, and embryonic mortality induced by delayed ovulation, could be connected and related to the poor perinatal conditions frequently observed in human MZ twins.


Triplet pregnancy in a subfertile woman treated with clomiphene citrate. A 26-year-old subfertile woman with a history of abortions at the 7-9th week was treated with Clomid, 50 mg for 5 days. A pregnancy resulted, which ended in the premature birth of a set of alive triplets that sex and blood-group determinations showed to be trizgotic. It is suggested that this production of a multiple ovulation in a woman with luteal deficiency be the result of excessive dosage of Clomid.


Pathogenesis of acute pancreatitis: pancreatic ductal-interstitial-vascular and lymphatic pathways. The generally accepted theory explaining the pathogenesis of pancreatic autodigestion (acute pancreatitis) is analysed. The pathways are discussed through which the content of the pancreatic duct system, the digestive enzymes, may escape to enter the acinar cells and the pancreatic interstices, together with the effect of the enzymes on the pancreatic vessels and thus on pancreatic blood flow. The potential consequences of vascular damage are described as well as the importance of pancreatic lymphatics in the transport of the escaped enzymes from the interstices. Although no definite answer can be given to the basic problem whether acute autodigestion of the pancreas is a result of some intra- or extra-acinar process, it is suggested that the intra- and extra-acinar processes are linked and are decisive in launching the pathological process.


Effect of immunosuppressive therapy on the serum glycoprotein levels in chronic aggressive hepatitis. The sera of 24 patients with chronic aggressive hepatitis receiving combined immunosuppressive therapy were studied for the concentrations of the carbohydrate components of glycoproteins and the IgG, IgA, IgM, alpha-2-macroglobulin, coeruloplasmin, beta-1-C-globulin and transferrin levels over a period of 2 years. Liver biopsy was performed repeatedly in 50% of the cases. On the evidence of the results, combined immunosuppressive treatment is regarded as apt to normalize the serum concentrations of IgG, IgA, IgM and to reduce those of alpha-2-macroglobulin and coeruloplasmin. Among the carbohydrate components of glycoproteins only the amount of hexose was reduced.


Serum lipids and lipoproteins in chronic liver disease. Serum cholesterol, triglyceride, total lipids and the lipoprotein pattern were studied in 169 cases chronic liver disease confirmed by biopsy. On the ground of the immunological and morphological results the patients were classified into five groups. In chronic persistent hepatitis no significant abnormality was found. In chronic aggressive hepatitis and in cirrhosis of the liver the serum cholesterol level was significantly reduced. In fatty infiltration of the liver the serum cholesterol, triglyceride and total lipid concentrations were significantly increased, as compared with the normal values and with the figures obtained in the cases of chronic inflammatory liver disease. In the cases of cirrhosis with additional diabetes the lipid values were likewise increased. In chronic aggressive hepatitis and in cirrhosis of the liver the levels of pre-beta and alpha lipoprotein were decreased, in fatty infiltration of the liver those of beta and pre-beta lipoprotein were increased.


Carbohydrate metabolism in various types of hyperlipoproteinaemia. Insulin secretion has been studied after an oral glucose load in 81 patients with primary hyperlipoproteinaemia and 15 control sugjects. Glucose tolerance was reduced mainly in Type IV, and to a lesser extent in Type IIB hyperlipoproteinaemia. Insulin secretory response to glucose was reduced in Type V and heterogeneous in Type IV hyperlipoproteinaemia. No correlation was found between the triglyceride level and the rate of insulin secretion.


Diagnostic evaluation of gastric analysis (test meal) in Hungary. On the basis of information received from 128 medical wards, the frequency of gastric analysis (test meal) used as a clinical diagnostic procedure, the spreading of the different methods and other problems connected with the examination are analysed. In about 3/4 of the institutions the test meal is performed in patients with all kinds of gastric complaint. This incidence decreases to 50% if the X-ray finding is positive. As acid-stimulants caffeine and a moderate dose of histamine are used most frequently. Of the data supplied by the test meal, the value for acid concentration (acidity) is registered by most of the examiners. The authors consider it as suprising that outdated methods such as a qualitative lactic acid assay (47%), isolation of Boas-Oppler's bacillus (25%) and of sarcinas (21%) are still in frequent use. The data are compared to the results of a similar survey made in England.


Regulatory hyperparathyroidism: the role of C-cell hyperplasia. Four cases with clinical and biochemical evidence of hyperparathyroidism are reported. The syndrome was due to DHT-intoxication of iatrogenic origin in the first case to histologically confirmed C-cell hyperplasia of the thyroid in the three others. The collective term "regulatory hyperparathyroidism" is porposed for the syndromes which, in distinction to secondary parathyroidisms, have a pathogenesis other than a negative calcium balance. Management of the syndrome is discussed with particular emphasis on the removal of the TCT-producing hyperplasia or adenoma, and the restoration of the electrolyte balance.


Heart block: histological and clinical features. The clinical types of A-V-block and the localization of the underlying lesion to the conduction pathway have been examined in 25 patients. On the evidence of the post mortem studies the lesions were of the following types: 1) Necrosis or fibrosis of ischaemic origin: 13 cases; 2) lesions of inflammatory character: 5 cases; 3) nonspecific lesions; 6 cases; 4) malignant infiltration: one case. Correlations between the site of lesion and the clinical type and pattern of block could be demonstrated in a large proportion of the cases. The characteristic features of the individual types of block and their localization are discussed and a review of the literature is given.


ECG changes in benzene, toluene and xylene poisoned rats. Electrical activity of the heart was studied in acute, subacute and chronic benzene, toluene and xylene poisoning by means of NEK-2 type apparatus in CFY male rats. In the early period of acute intoxication benzene and its methyl derivatives, injected either intraperitoneally or subcutaneously or administered by inhalation did not cause changes in the ECG. Intravenously injected toluene induced a rapid and permanent decrease in blood pressure, in higher doses respiratory paralysis. In acute inhalation toluene and xylene poisoning the anesthesia was followed by respiratory paralysis, bradyarrhythmia and asystole, while inhalation of benzene induced respiratory paralysis followed by ventricular fibrillation. Subacute poisoning with benzene, toluene and xylene caused disorders in repolarization and arrhythmia. The degree, incidence and development of these phenomena depended on the dose and the duration of exposure. The effect of benzene influencing ECG was appreciably more intensive than that of toluene or xylene. Owing to the high number of spontaneous ECG changes due to ageing, it is difficult to evaluate the effect of chronic exposure to the agents under investigation.


Modification of the biologic dose to normal tissue by daily fraction. Model for calculating normal tissue tolerance. A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD in predicting rib fracture. Neither model predicts pericardial effusion. In no case were the results  of BIR inferior to those of NSD.


Anti-oestrogen therapy of advanced mammary carcinoma. Forty mg daily of tamoxifen (Nolvadex) was administered orally to 89 patients with advanced soft tissue mammary carcinoma. At two months 43 per cent of the patients responded. At 6, 12 and 18 months, 42, 35 and 32 per cent, respectively, were still responding to therapy. The side effects were limited, fatique being the most frequent complaint. Oestrogen dependent side effects were not encountered. The therapeutic effect of tamoxifen is similar to that of oestrogen, but the side effects are less.


Scanning electron microscopy of cells in the lymph of the human thoracic duct in advanced malignancies. At scanning electron microscopy of cells from the lymph of the thoracic duct, collected by cannulation of patients with malignant tumours of different types, lymphocytes and red blood cells were found, but few malignant cells. The latter came from patients with pulmonary carcinoma and mammary carcinoma with lung metastases. Various abnormal shapes of the red blood cells were observed, possibly due to extrinsic factors such as administered drugs of abnormal metabolites from the malignant disease. The lymphocytes had no consistent pathologic shape, but appeared to act as immunologic, active cells against the malignant cells in the thoracic lymph.


Radiation sensitizing effect of diamide on human cells cultivated in vitro. Human cells of line NHIK 3025 were irradiated suspended in growth medium (E2a) in absence and presence of diamide under aerobic and extremely hypoxic (less than 4 ppm O2) conditions. A sensitizing effect of diamide was found for doses exceeding 8 Gy (800 rad) on cells irradiated under extremely hypoxic conditions in presence of diamide of concentration 200 micrometer, whereas no significant effect was observed for 20 micrometer.


Histochemical and morphometrical changes in the adrenal glands in the course of circulatory failure. The histological and biochemical changes in adrenal function has been studied in 50 male cats with circulatory failure. The adrenal glands were examined by morphometric, histochemical and histoenzymological methods after a preliminarily study of the histoenzymological profile of the adrenal glands in intact animals. Five hours after hypotension induced by intravenous injection of trimethaphan and 5 hours after a single massive bleeding, a decrease in adrenal function was observed. Adrenal insufficiency especially of the glucocorticoid release in the course of acute circulatory failure can be considered as a peculiar adaptation of the organism to preserve its life. The demonstrated decrease of adrenal function in the first hours of hypoxia may help in planning hormonal therapy under suitable conditions.


Development of collagenous fibres in autologous and preserved homologous tendon grafts. Collagen synthesis has been studied in preserved autologous and homologous tendon grafts, applied in dogs. The stages of collagen morphogenesis observed in the synthetizing fibroblasts appearing in the decomposing original structure of the transplants as well as in the extracellular ground substance are described. The results suggest that autologous tendon grafts and homologous ones preserved by irradiation, stored in cold physiological saline and beta-propiolactone, are rebuilt within eight weeks; meanwhile the original collagenous fibre structure is decomposed. When other preserving procedures such as deep-freezing or gamma irradiation are applied recomposition of the graft is retarded or fails to occur; the result is a cicatrizing adhesion.


Selective sympathetic denervation induced by 6-hydroxy-dopamine in the small intestine. The structure of the nerve fibres in the intact and neurally isolated intestine of the cat was studied after 6-OHDA treatment by fluorescence and electron microscopy. A gradual disappearance of green fluorescence in the monoaminergic fibers was observed. Degeneration of nerve fibres containing 30--60 nm agranular and 30--60 nm densecore (granular) vesicles could be seen in all layers of the small intestine. Sporadically, degeneration of the presynaptic elements occurred also in the synapses of myenteric ganglia. A large number of degenerating fibres could be observed in close relation to blood vessels. These were thought to be monoaminergic because 6-OHDA selectively affected their terminals. In the chronically isolated small intestine degenerated nerve processes could not be observed following 6-OHDA treatment. It is concluded that the intrinsic nerve elements do not contain monoamines. Accordingly, the previously observed yellow fluorescence of the nerve elements of the isolated small intestine might be due to some other kind of neurotransmitter, possibly tryptamine.


Parenchymal destruction and arterial changes (haemodialysis intimal fibrosis) of glomerulonephritic kidneys in chronic intermittent haemodialysis. The kidneys of 13 chronic diffuse glomerulonephritis patients who had been subjected to chronic intermittent haemodialysis were compared with those of 6 patients treated in the conservative way. Their renal parenchyma was examined with a semiquantitative histological method and advanced complete destruction of the glomeruli was demonstrated in the dialysed cases. There was no perceptive difference in the distribution of the various grades of damage of the recognizable glomeruli and tubules. With the exception of the chronic lobular glomerulonephritis cases, a marked obliterative mucoid intimal proliferation ("haemodialysis-intimal-fibrosis") had developed in the dialysed glomerulonephritis patients. It affected the renal arteries of all size from the segmental to the interlobular arties. Haemodialysis-intimal-fibrosis did not develop in the additionally examined 13 dialysed chronic pyelonephritis cases nor in 8 such treated conservatively. The change seems to be characteristic, but not specific, for chronic diffuse glomerulonephritis treated by chronic intermittent haemodialysis.


Reversibility and interaction with hepatic regeneration of toluene induced liver injury. Acute and subacute toluene poisoning was induced in CFY rats. Routine histological, enzyme histochemical and electron microscopic investigations revealed that following discontinuation of exposure, the hepatic changes indicating an enhanced load on the detoxicating function (increased SDH activity, increase of mitochondria and smooth endoplasmic reticulum, decrease in Best carmine staining and PAS positivity) as well as degeneration (dilation of endoplasmic reticulum, accumulation positivity) as well as degeneration (dilation of endoplasmic reticulum, accumulation of autophagous vacuoles) show a rapid regression. The toxic effect of toluene and the functional load on the liver is thus reversible. In another series, toluene exposure was combined with partial hepatectomy. It has been established by routine histological, enzyme histochemical and electron microscopic techniques as well as by quantitative light and electron microscopic methods that the two interventions show a peculiar interaction: hepatic regeneration following partial hepatectomy inhibited the effect of toluene. On the other hand, the rate of regeneration was not influenced by toluene.


Myeloid metaplasia in the spleen after acute haemolysis. Copper sulphate, phenyl hydrazine and antiserum were administered to adult albino rats to produce equivalent haemolysis. Red pulp activity was studied for myeloid metaplasia after 24, 48 and 72 h, 5 and 7 days. Myeloid metaplasia was not related to the marginal zone proliferation. The activity rose rapidly with all the three agents and followed a similar curve despite the different patterns of haemolysis and erythrophagocytosis. Splenic erythrophagocytosis acts as a powerful feedback for splenic myeloid metaplasia. With copper, the release of reticulocytes and iron binding in haemoglobin is rapid as compared to the other agents, in spite of the initial lag phase, due to its effect on cellular metabolism.


Frequency of juxtaglomerular granulated cells in the mouse kidney. Studies of 23 untreated adult mouse kidneys revealed that in mouse kidney sections the frequency of juxtaglomerular granulated cells as compared to the glomeruli is 38.5 +/- 1.79%, the value for the JGI, 71.8 +/- 3.93. Following 100 glomeruli through complete serial sections prepared from a single mouse kidney, it was shown that in the cortex of the mouse kidney all juxtaglomerular apparatus related to the glomeruli contain renin-producing modified smooth muscle cells with granulated cytoplasm.


A glycoprotein precipitate in the blood vessels of kidneys stored in cold homologous blood. Dog kidneys were stored three hours at 4 degrees C in heparinized homologous blood. Their histological examination revealed the presence of a homogeneous precipitate in the glomerular capillaries and afferent and efferent arterioles, and histochemical analysis indicated that it consisted of glycoprotein. It is tentatively suggested that the substance is cryoglobulin, a conclusion supported by the disappearance of the deposit on reimplantation of the kidney.


Alterations of the Z-band in cardiac and skeletal muscles. The heart muscle may react to various hypoxic damaging effects (e.g.N2, CO, haemorrhagic shock, electroshock) by identical responses similarly as in the case of skeletal muscle damages. One of the early manifestations of the process is the alteration of the Z-band, which is considered pathological. The alterations of the Z-band region precede the changes of the mitochondrial and sacrotubular systems and might form the morphological basis of functional changes induced by hypoxic effects. The alterations observed are differentiated from the hypertrophy of the Z-band. In the development of the alterations of the Z-band the role of other factors (e.g. calcium metabolism, sacroplasmatic membrane changes) is emphasized.


The cytoarchitecture of the adrenal medulla in the rat. The disposition of adrenaline and noradrenaline storing cells in the adrenal medulla has been studied in the rat. It has been demonstrated that no morphological or functional reason exists for the follicular designation of clumps of chromaffin cells in the medulla. No significant difference was found between the outer and inner zone as regards the frequency of NA cells by morphometric and statistical methods. The cytoarchitectural differences between adrenaline- and noradrenaline-storing cell arrangement are described. Special features of the interrelation between noradrenaline storing cells, cortical cells and the connective tissue framework are stressed. The light and electron microscopic appearance of two types of cortical cells, assumed to represent different states of functional activity is described.


Central core in the spinal grey matter.

Central core in the spinal grey matter. Golgi--Kopsch impregnated spinal cord sections of adult cats revealed a regular orientation of the dendrites in the intermediate region forming a circular or elliptical grey matter. The orientation of the dendrites is strictly transverse in the central core. A new interpretation of the spinal grey matter is proposed by viewing the dorsal, lateral and ventral horns (or columns) as crest-like appendages attached to the rod-like central core. A structural and possibly functional similarity between the central core and the brain stem reticular formation is emphasized.


Intimate contact between human yolk sac endoderm and haemopoietic precursor cells. Although the localization of embryonic haemopoietic cells in the endodermal epithelium of the human yolk sac had been discovered several decades ago, the nature and significance of the localization were dubious, and it was supposed that light microscopic pictures represent technical artifacts. Our ultamicrographs now demonstrate that at 16--26 mm CR-length there is an intimate contact between yolk sac endoderm and free haemopoietic precursor cells: apart from interdigitations various types of intercellular contact could be discovered. These contacts, especially the gap-like ones with associated electron dense cytoplasmic areas speak for intercellular communication, i.e., the role of endoderm in early human embryonic haematopoiesis appears likely. The demonstrability of these contacts, however, does not mean that endodermal associations are indispensable for haemopoietic differentiation.


Blood supply of the rat hypothalamus. IV. Retrochiasmatic area, median eminence, arcuate nucleus. The vascular supply of the rat hypothalamo-hypophyseal complex was studied by aid of a double injection technique (two dyes different in colour injected successively). The vascular bed of the median eminence, the arcuate nucleus, and the retrochiasmatic area are intimately interconnected among themselves, but isolated from the vascular system of all other parts of the hypothalamus. The arterial supply of this ensemble of the medial basal hypothalamus is common from the hypophyseal arteries, via the primary plexus and the specific vascular loops of the median eminence. From here a separation of the vascular bed leads the blood flow towards the pituitary portal vessels on the one hand, and over a subependymal vascular network towards the arcuate nuclei on the other. The venous drainage of the arcuate nuclei and the retrochiasmatic area is secured by a special set of tuberal and retrochiasmatic veins. --The unity of the vascular bed of the median eminence, arcuate nucleus, retrochiasmatic area complex, with a blood flow largely in the direction indicated by this sequence, is of considerable importance for the interpretation of the results of experimental interference with this region.


[Clinical and hematogenic considerations on 2 cases of cerebral venous thrombosis occuring during the use of oral estro-progestational preparations]. The authors illustrate the clinical peculiarities and the laboratory data of thrombotic accidents as complications of oral contraceptives and other estrogen-containing drugs, concerning modern literature. Moreover, they describe two cases of cerebral venous thrombosis verified in Neuropathology Department of Maria Vittoria Hospital-Torino. The problem of prevention of these accidents is debated in the second part of the article.


[Analysis of nitrocompound pesticides by potentiography (author's transl)]. This paper describes a potentiographic technique developed for determining nitrocompound pesticides. The statistical analysis of the results showed that it is precise and accurate. Rapidity is another important characteristic of the developed potentiographic technique. It is not specific and for that in some cases a column chromatographic cleanup is necessary.


[Kinetics of the binding 14C-DDT-and haemolymph lipoproteins of Periplaneta americana (author's transl)]. A study of the kinetics of the complexation of the 14C-DDT and lipoproteins of the haemolymph of Periplaneta americana (L.) was made, the method employed was that described by WINTER et alii (7). It was found that the above complex was unstable when kept at low temperatures (5 degrees) for more than twenty four hours; the incorporation of 14C-DDT in the proteic fraction increased with temperature up to 42 degrees C, and at least 6 hours of incubation were necessary to bind the 14C-DDT to the lipoprotein.


[Morphology of experimental argyrosis in kidneys]. Prolonged per os administration of silver nitrate solution in rats will result in the development of experimental argyrosis with particles of silver in the kidneys being deposited mainly in the glomerular basal membranes. Apart from that, particles of silver in the glomeruli were also found in the mesangioma and, in minor quantities, in podocytes and endothelial cells. Outside the glomerular structures, silver was found deposited in tubular basal membranes, in the proximal tubule epithelium and minute vessel wals. -- A discussion is presented of the possible mechanisms involved in the development of such deposits, as well as of the relationship between intravital silver depositing and some of the tissues affinity to silver, a property taken advantage of in histological methods.


[Experimental administration of a fatal dose of antiglomerular antibodies]. The administration of a sufficient dose of heterologous antibodies against renal glomeruli in rats produces symptoms of respiratory insufficiency and pulmonary oedema causing death of the animals. Under these experimental conditions the basic pathogenic mechanism appears to be binding of the injected antibodies on the basement membrane structures of pulmonary capillaries resulting in their damage. Such changes are followed by widespread haemorrhagic exsudative changes in the lungs. Localization of the injected antiglomerular antibodies has been studied with the aid of immunohistochemical methods and in addition, by a method using antibodies labelled with radioactive isotopes of iodine, the so-called "paired administration technique". After the administration of a lethal dose of antiglomerular antibodies, they later appeared to be predominantly localized in the lungs. This fact correlates well with the idea of the effect of the antibodies upon pulmonary parenchyma in the present experiment. A remarkable finding was a rather high localization of the injected antibodies in the liver parenchyma which could be explained either by a cross reaction between the antibodies and the antigens of hepatic vascular spaces, or by a shock reaction associated with heart failure and circulatory disturbances.


[Functionally active tumor of the carotid body]. The clinical and biochemical pictures of a woman of 60 suffering from paroxysmal hypertension appeared to be clear evidence of a functionally active neoplasm of the sympathoadrenal tissue. A surgical operation ruled out the possibility of the tumour being localized adrenally so that the actual site of noradrenaline release was never found during the patient's lifetime. An autopsy discovered the presence of a carotid body tumor sized. 4.5X3X3 cm. The histological picture, electron microscopy as well as the positive isolation of noradrenalin all seemed to offer clear evidence of a functionally active tumour although the chromaffin reaction was negative. This is just additional evidence of the fact that the carotid body does belong among sympathetic paraganglia and that the chromaffin reaction is not sufficiently sensitive and reliable either for the determination of biogenic amines in the tissue or for a clear, unequivocal detection of functionally active tumours of the sympathetic.


[Kinetics and morphology of immune reaction cells in the spleen studied using the immuno-cyto-adherence reaction. V. Secondary response and its modification by whole-body irradiation at different intervals following administration of antigen]. Observations were made of the course of secondary immunological response, using the immuno-cyto-adherence method under the influence of 450 r general body irradiation on murine spleen following secondary ram erythrocyte immunization. Irradiation was applied 24 hours, 72 hours and 6 days after an i.p. administration of antigen. Irradiation was immediately followed by an absolute as well as relative drop in RFC number and by an overall drop in splenic cell number. In case of irradiation applied prior to reaching the secondary reaction quantitative maximum, there was a development of the increment and another RFC quantitative maximum was reached between days 15--20 after irradiation. Small and medium size lymphocyte values were seen decreasing immediately after irradiation. Where irradiation took place prior to reaching the quantitative maximum of a normally proceeding anamnestic reaction, large lymphocytes constituting RFC were increasingly represented after a certain period of stagnation or even without it. Plasmatic series cells on irradiation tended to  increase their total share to become a prominent cell element after delayed quantitative RFC maxima had been reached and to reach complete predominance towards the end of the period of time under observation. A relative increase in the proportion of macrophages was seen immediately after irradiation.


Rehabilitation of the voice after pharyngolaryngectomy and skin repair. I. Cineradiography. Eleven patients who had undergone pharyngolaryngectomy and who had poor or no speech were studied to find out why. An absent oesophageal stripping wave and the presence of a 'sump effect' are described. It is concluded that these are two positive anatomical factors mitigating against the acquisition of oesophageal speech in pharyngolaryngectomized patients.


A morphometric study of the laryngeal saccule and sinus. A morphometric study of 111 larynxs from both sexes was performed with the initial intention of assessing the incidence of asymptomatic laryngeal pouches. Certain basic measurements were made also to determine the dimensions of the laryngeal saccule and sinus relative to the height and width of the larynx in the two sexes. Asymptomatic pouches were found in 2 patients, one from each sex and there was no obvious difference in the height of the saccule relative to the height of the larynx in the two sexes. However, since the male larynx was deeper in the anteroposterior plane relative to its height, the male saccule tended to be relatively shallower than the female.


Late recurrence or radiation induced cancer of the larynx. Twenty five patients with squamous carcinoma of the glottis (T1a and T1b) had undergone successful irradiation. Many years later they developed a so-called  late recurrence. The following evidence shows that these 'late recurrences' are radiation induced: the interval of 5-18 years (mean 9.9 years) between the first and the second cancer correlates with the interval seen usually in radiation induced malignancy, recurrences generally appear during the first 2 years after irradiation, all the second cancers were found in the previously irradiated area, in patients treated by surgery only, late recurrences are extremely rare, histological examination clearly shows that the second carcinoma originates from the squamous epithelium and not from dormant nests in the deeper layers of the vocal cord. These factors should be taken into consideration when deciding between surgical or radiation therapy in younger patients with high life expectation.


The place of cytology in laryngeal diagnosis. A cytological procedure providing useful supplementary information in the diagnosis of laryngeal malignancy is described. Of 51 patients, 22 had complete correlation with histological examination in confirming a benign condition. Twenty patients had complete correlation in confirming a malignant lesion. Five patients showed cellular atypia in the presence of benign conditions. Three showed atypia, of which 2 were malignant, 1 being unstable histologically but with no evidence of frank malignancy. Ten patients had been irradiated previously; in all cases the distinction between residual disease and no evident disease was correctly diagnosed with respect to the histological appearance.


Cardiac arrest in otorhinolaryngology.

Cardiac arrest in otorhinolaryngology. A study has been carried out of 42 episodes of cardiac arrest related to 90 000 otorhinolaryngological operations. The basic pathology, factors precipitating the arrest, and the results of treatment are analysed. Clinical areas presenting special problems are the surgery of cancer of the postcricoid area, deliberate hypotension, anaesthesia for laryngoscopy and respiratory obstruction.


Temporary threshold shift and the auditory evoked response. A preliminary report. A preliminary study was performed on 5 normal subjects to investigate and compare the reduction and recovery of the auditory evoked response (AER), and to compare this with the temporary threshold shift (TTS) that occurs with fatiguing sounds. The findings are discussed in relation to the basic nature of the AER.


Facial spasm.

Facial spasm. There are many varieties of abnormal facial movement. This paper discusses hemifacial spasm and blepharospasm in particular. A technique found useful for the symptomatic relief of idiopathic hemifacial spasm is described, and experience with its use on 15 patients also described. Experiences in the operative treatment of 6 patients with essential blepharospasm are recounted.


Transtympanic electrocochleography in the diagnosis of retrocochlear tumours. Transtympanic electrocochleography has been used as a diagnostic procedure in over 250 adult patients with sensorineural deafness. No complications have been encountered. Among these patients vestibulocochlear Schwannoma (acoustic neuroma) has been confirmed in 56 ears while 11 other ears have been found to be affected by other space-occupying lesions. As a result of our observations in these patients, we would like to propose that there are at least three separate criteria to be considered in reaching or strongly suspecting a diagnosis of such pathology. These are broadening of the action potential (loss of P1), observation of a clear microphonic response, and preservation of the action potential even when using stimulus intensities which are not audible in the patients' affected ears. The merits of each of these criteria are discussed and compared with other clinical and operative findings. With the electrocochleographic techniques now employed in searching for acoustic neuromas, false negative results are rare though false positive results are still obtained.


Growth rate and recurrence of residual epidermoid cholesteatoma after tympanoplasty. One hundred and forty-one consecutive patients with chronic otitis media and cholesteatoma treated mainly by open surgical techniques between 1965 and 1972 were studied to investigate the phenomenon of residual cholesteatoma. The average rate of emergence of residual cholesteatoma was 0.25% of the cases per month during the first 5 years, after which the rate of discovery almost ceased. Observed cumulative frequencies of recurrence were 1.4% at 10 months, 14.9% at 5 years and 17.0% at 8.3 years postoperatively. The null hypothesis of no apparent predilection of cholesteatoma for recurrence at any one site was retained. Parameters of growth rates of epidermoid cysts arising from residual cholesteatoma were estimated. Epitympanic cysts grew fairly rapidly, doubling in diameter every 10 months. Mastoid cysts were slower, doubling in diameter every 25 months. Results for the mesotympanum were inconclusive. The practical implications of this information for the management of future cases is discussed.


Percutaneous teflon injection of a vocal cord under fibre optic laryngoscopic control. The technique of percutaneous injection of Teflon paste into a paralysed abducted vocal cord using a fibre optic laryngoscope to observe and control the effect is described. Its use in vocal cord paralysis caused by inoperable bronchogenic carcinoma and the results in 14 patients are discussed.


A second method for induction of a transmissible entity in the control of cancer in mice. Spontaneous tumour-bearing mice of the C3H/St and subline C3HB/St inbred strains received injections of three nucleosides, adenosine, 6-methyl adenosine, and 5-methyl cytidine, prepared in the same molecular concentration as they had occurred in an alcohol-soluble liver extract which in previous work had suppressed tumour growth. Two transmissible entities appear to be present and they show different degrees of effect upon the growth and regression of spontaneous tumours of mammary gland origin (adenocarcinoma). The first transmissible entity (TE) occurred in the lineal descent of mice following injection of the liver extract. The second entity (TE2) appeared following injection of 5-methyl cytidine. TE manifested its maximum effect in suppressing cancer in mice during the 20th generation of a lineal descent following the injection of the original liver extract into a mother of the cancer proband. TE2 appears to be optimal in controlling cancer in the F11 generation of a second lineal descent derived from an original cancer proband of the C3H/St inbred strain injected with 5-methyl cytidine.


Salivary gland chromosomes of Lucilia cuprina (Diptera, Caliphoridae). The salivary gland chromosome complement in Lucilia cuprina consists of five pairs of autosomes and two sex chromosomes X and Y, all with characteristic banding patterns. A standard map for the salivary gland chromosomes of this species has been prepared, and compared with the known map of Lucilia cuprina dorsalis from Australia. The differences in their banding patterns indicate the existence of different varieties within the same species.


Ultrastructural and physiological changes induced by atractylate in the canine myocardium. The myocardial cellular response to the cardiac glycoside atractylate, a known inhibitor of mitochondrial adenine nucleotide translocation, was examined physiologically, morphologically, and morphometrically in eight dogs. An isolated in situ segment of left ventricular tissue was employed in these experiments to eliminate collateral flow and the potential for large sampling error. It was found that atractylate infusion rapidly induced physiological and morphological changes suggestive of a loss of membrane regulation of ion flux in the arteriole, capillary endothelium, and myocardial cell. Also mitochondrial changes suggestive of adenine nucleotide translocase inhibition were observed. As these responses are similar to those induced by acute myocardial ischaemia, it is suggested that ischaemia and atractylate induce cell injury by similar mechanisms.


[Postnatal development of the adrenal gland in the rat (author's transl)]. Postnatal development of adrenocortical function of rats was studied. During the first week after birth the increase in adrenal weight was very slight. Consequently, the relative weight of the gland per body weight decreased progressively during the postnatal 14 days. However, adrenal corticosterone concentration showed a gradual elevation over this period of postnatal days. Adrenal corticosterone response to ether stress did not appear in male rats at 12 days of age, but a distinct response was observed in female ones at the same age. A sex difference in the duration of the stress-nonresponsive period is likely to exist in newborn rats. In accord with the stress-nonresponsive period, the thymus-lymphatic system showed a marked development. The pattern of circadian periodicity of plasma corticosterone levels in 21-day-old rats was somewhat different from that in adult rats. Peak value of the corticosterone rhythm was attained at 0300 in the infant rats. A sex difference was again noticed in the evening rise of plasma corticosterone level in these infant rats: the rise was steeper in females than in males. A significant circadian periodicity was observed in female rats at 14 days of age, but the periodicity was equivocal in male ones at the same age.


[Atrophy of adrenal gland and thymus following cortisol treatment in newborn rats (author's transl)]. Effects of neonatal treatment with cortisol on the mortality, growth rate, the weight of thymus, spleen and adrenal gland, blood lymphocyte counts and stress responses were examined in the rat. In rats treated with 1 mg cortisol the survival rate was only 13 percent, and in those given 0.75 mg the rate was 47 percent. Large doses of cortisol produced "wasting syndrome" and the animals died during a period from 5 to 13 days after the injection. Over the first week the body weight did not increase in rats injected with cortisol in doses of 1 and 0.75 mg. A marked atrophy of the thymus and a great reduction of the blood lymphocyte counts were observed in rats treated with large doses of cortisol. The development of spleen was temporarily inhibited. The adrenal gland was remarkably atrophied: the gland weight at 21 days of age was similar to that at birth and only 22 percent of the control value. In rats injected with 0.5 mg cortisol plasma corticosterone response to ether inhalation was not different from that of normal controls at 21 days of age. However, rats treated with 0.75 and 1 mg cortisol did not show plasma corticosterone response on exposure to a strange environment. The effect of several kinds of corticoids was also examined. Dexamethasone and betamethasone caused a marked atrophy of the thymus and spleen. Cortisol and deoxycorticosterone produced a large decrease in the adrenal corticosterone content. The effect of exogenous corticosterone was less in extent as compared with that of cortisol.


The use of fibroblast and epidermal growth factors to lower the serum requirement for growth of normal diploid cells in early passage: a new method for cloning. The proliferation of animal cells in tissue culture requires unidentified macromolecules that are contained in serum. Since serum is an extremely complex mixture, efforts to purify these growth-promoting components of serum have met only limited success. On the assumption that these growth-promoting macromolecules in serum are synthesized in active form in some tissue other than blood, we investigated the possibility that they may be purified more readily from specific organs than from serum. We have concentrated our efforts on two likely sources: the pituitary gland, since partially-purified preparations of pituitary hormones have been reported to stimulate the growth of cells in vitro and brain, since neural tissue is essential for the regrowth of amputated limbs in lower vertebrates capable of regeneration. Both pituitary and brain have yielded a strongly mitogenic polypeptide that we call Fibroblast Growth Factor (FGF). FGF was named on the basis of early studies demonstrating its effect on fibroblastic cells: 3T3 cells, amniotic fluid-derived cells, and fibroblasts from human foreskin and mouse embryos. Further work has revealed that FGF promotes the growth of several other mesoderm-derived cell types including adrenal cells, chondrocytes, myoblasts, vascular smooth muscle cells, and vascular endothelial cells. The effect of FGF will be compared to that of EGF and its use for cloning mammalian cells will be described.


Large-scale cultivation of cells in closed systems: stationary and moving. Basic metabolic differences have been observed for cell cultures propagated in conventional stationary or rotating systems. The influence of these differences on virus characteristics is largely unknown but could be significant in maintenance of genetic stability of attenuated strains. Current requirements for good manufacturing procedures prompted the development of closed systems for both stationary and rotating cultures. Both are suitable for large-scale virus production. The methods will be described along with data on yields of a number of vaccine viruses.


The large-scale cultivation of diploid cell strains in microcarrier culture. Improvement of microcarriers. The use of diploid cell strains for virus vaccine production is mostly retarded by the inefficient culture techniques used for the propagation of these cells. The microcarrier culture system might be a good solution for this problem. DEAE-gels appear to be the most satisfactory microcarrier. The best results are obtained by using DEAE-gels with a rather low anionic exchange capacity or at higher capacity after coating with polymers.


Development of a perfusion culture system for production of biologicals using contact dependent cells. Design and evaluation of a new type of culture vessel for contact dependent cells is described. Cells are grown on both sides of stationary glass plates in a laminar flow of medium supplied from separate reservoirs. Construction and operation of vessels ranging in growth surface from 0.02 to 10 m2 is relatively simple and there are no moving parts. Cells can be inspected by low power microscopy in the usual way. Evaluation of this equipment was carried out using the human diploid cell line MRC-5. Saturation densities of up to 1 million cells per square centimetre of growth surface were obtained where appropriate medium volumes were used. Application of this sytem to other cell types and the production of biological products is briefly discussed.


Updated results on the karyology of the WI-38, MRC-5 and MRC-9 cell strains. Data concerning cumulative results obtained from studies of the karyology of the characterized MRC-5 cell strain and the MRC-9 strain at present being characterized, indicate that these cells have karyological characteristics similar to each other and to the extensively studied WI-38 cell strain. The general inference from these studies is that the cells are karyotypically stable and that their karyological characteristics are within the limits recommended for normal cell populations.


Reappraisal of karyological monitoring of diploid cell substrates. The practical aspects of present requirements for karyological monitoring of diploid human fibroblasts used in vaccine production are critically re-examined. A brief review of known chromosomal instabilities and their correlations with neoplasia and with in vitro conversions of cell growth is presented and discussed in relation to karyological criteria in the selection of mammalian diploid cell substrates. It is proposed that extensive experience with the growth and karyological characteristics of human diploid fibroblast cell strains of embryonic origin may warrant the reduction or elimination of karyological monitoring of production lots. Additional requirements for characterization of cell strains for approval as substrates for vaccines are suggested which involve evaluations of chromosomal stability based upon (a) viral transformation rate and (b) aberration production rate in response to x-irradiation.


The need for non-cultural methods for the detection of mycoplasma contaminants. Mycoplasmas are common contaminants of cell cultures and are of great importance because of the deleterious effects they have upon the infected host cells. Routine detection testing usually relies upon cultural methods and demonstration of characteristic colonies on agar. Questions as to the efficacy of this method have been raised because of increasing realization of the presence of "non-cultivable" mycoplasmas. Several non-cultural detection methods have been developed to aid in the detection of these fastidious microorganisms. These methods include morphology by light and electron microscopy, immunofluorescence, enzyme assays, autoradiography, sucrose gradient separation, altered transport of nucleic acid precursors and altered nucleic acid profiles. A comparison of the relative sensitivities of these methods will be outlined. The need for, and the feasibility of non-cultural detection methods as quality control tests in human virus vaccine production will be discussed.


Tumourigenicity testing in immunosuppressed mice: advantages and disadvantages. Optimal conditions for the detection of malignant cells substrates were investigated. Three approaches were used: (1) neonatally thymectomized, antithymocyte serum (ATS) treated mice, (2) thymectomized, lethally irriadiated, bone marrow reconstituted (T-B+mice, and (3) congenitally athymic nu/nu (nude) mice. All three systems successfully distinguished between normal and malignant cell lines. However, differences were observed between different colonies of nude mice as to their capacity to support progressive growth of certain tumours. Advantages and disadvantages of the immunosuppressed mouse model system will be discussed. They will include: (a) detection of malignant cells in mixed populations, (b) need for different routes of inoculation for different cell types, (c) comparison with other malignancy testing systems, (d) long term versus short term immunosuppression.


Production and control of rabies vaccines made on diploid cells. Introductory remarks on the advantages of antirabies vaccines obtained from human diploid cell cultures in comparison with brain tissue vaccine and duck embryo vaccine. The characteristics of these new types of vaccine are: (i) high antigenicity, (ii) rapid development of antibodies, (iii) absence of adverse reactions even when the booster inoculation was given two years later. The disadvantage is the high cost of production to obtain a highly purified product.


Observations of the incidence of structural abnormalities in the chromosomes of WI-38 cells prepared for vaccine manufacture. Chromosome monitoring of 500 batches of WI-38 cells prepared for vaccine manufacture involved examining 50-60,000 metaphases at p31-32. Results collected over 6 years showed the mean incidence of aneuploidy and breaks to decrease slightly, whereas the incidence of structural abnormalities followed a sharply rising trend, eventually reaching a level where a substantial proportion of cell batches exceeded the limit set for this parameter for vaccine substrates. No technical or cultural factor accounted for the trend which appeared to be correlated with the date of receipt of the seed ampoule. The confidence limits set for this parameter in 1971 were regarded then as provisional. It is suggested that in the light of the observations reported, the position should now be reconsidered.


The significance of positive controls in testing the oncogenic potential of cell material for virus vaccine production. For all the parts involved in the production and control of virus vaccine it is important that controls of the cell material should be carried out under optimal conditions for the detection of any abnormal characteristics of the cells. The experiments reported here attempt to establish some of the optimal parameters for testing out the tumor-inducing properties of a human diploid cell culture. All experiments were carried out on 6-week old Syrian hamsters and the main objectives were: (i) to devise an optimal immunosupression scheme and (ii) to find a more suitable positive control for testing the oncogenic potential of the human diploid cells. The anti-hamster lymphocyte serum proved to be a more potent immunosuppresser than hydrocortisone succinate as seen from the development of tumors following injections with KB cells; this scheme was subsequently used in assessing the usefulness of KB and Swiss-12 cells as positive controls. The experiments lend support to the suggestion that a heteroploid fibroblastic culture (such as Swiss-12) should become a standard positive control since not only are the tumors so obtained larger and less prone to early necrosis but, more important, they bear a closer resemblance to the kind of tumors likely to be induced by the diploid cell cultures being tested.


Post-exposure use of human diploid cell culture rabies vaccine. 880 individuals, 120 of which were exposed to rabid animals, were immunized pre- or post-exposure with 2 different BPL-inactivated and concentrated rabies vaccines prepared in HDC strains WI-38 and MRC-5. The vaccines were well tolerated and no major side effects were observed after primary immunization with 3-10 doses or 1 booster vaccination. The dynamics of neutralizing, antibody formation and persistence of antibodies in 4 different groups of vaccinees are described. The groups were vaccinated pre-exposure (I) on days 0, 28 and 56; (II) on days 0, 7 and 14; (III) on days 0, 3, 7 and 21; and (IV) post-exposure on days 0, 3, 7, 14, 30 and 90. High antibody levels--persisting for at least 30 months--were obtained in all patients. The CFT, using a concentrated and purified virion antigen, was highly specific for rabies virus antibody demonstration. Since in some 50 patients under severe risk, after having been bitten and/or scratched by proven rabid animals, not a single breakthough of immunity was observed during an observation time between 1/2 and 3 years, the protective effect of the HDCS-rabies vaccines seems to be excellent. With regard to their high immunogenicity and extremely low reactogenicity, the new HDCS-vaccines can be recommended for prophylactic and post-exposure immunization of man without any reserve. Data on simultaneous application of homologous anti-rabies gammaglobulin from man (20 I.E./kg body-weight) and HDCS-vaccines are also presented and discussed.


Karyological characterization of WI-38 cells used in the production of vaccines. According to the valid requirements, samples of WI-38 cells taken prior to the final subcultivation for vaccine production by the manufacturer, were reconstituted, subcultivated and investigated in our control laboratories. Chromosome monitoring was done using permanent orcein stained slide preparations for direct evaluation and photographs of all selected cells for exact counts, scoring for breaks and karyotype analysis in the case of abnormalities. The tabulated summary of karyological analyses on more than 2000 cells shows that with one exception, the chromosome abnormalities did not exceed the upper limits of karyological acceptability. Photographs of abnormalities detected are presented as well as metaphases and reconstructed karyotypes. Our data are compared with those provided by the manufacturer. Obvious discrepancies in the frequency of abnormalities might be due to higher passage levels of the identical cell material tested by us and to slight differences in the methods of preparation and evaluation.


Production of RA27/3 rubella vaccine and clinical results with the vaccine. Adaptation of rubella virus to human diploid cell strains was achieved in 1964, with attenuation in the same cells being accomplished by 1967. The production of rubella vaccine in HDCS is featured by the long period required to build up high titer. High multiplicity of infection gives optimal results. Since rubella virus does not produce a cytopathic effect in HDCS, virus harvests must be made blindly and titrated individually before pooling. A unique feature of this cell-virus relationship is the continuous virus production which takes place for months. For vaccine purposes, however, virus-containing supernatant fluids may be harvested each 48 hrs from the 5th to the 21st day post-infection. Lyophilization presents no particular problems and final titers in ampoules can be as high as 10(5.0) PFU, which represents about 100 subcutaneous doses. Control of rubella vaccine presents only the problem that viral CPE is absent or mild. Therefore the presence or absence of virus may have to be determined by interference. Titration of rubella virus produced in HDCS must be by plaquing in RK13 rabbit kidney cells or by interference in cynomolgus monkey kidney cells. Rubella vaccine (RA27/3 strain) produced in HDCS has been more immunogenic than other strains and retains an ability to infect intranasally as well as subcutaneously.


Use of human diploid cell MRC-5, for production of measles and rubella virus vaccines. A further attenuated strain of measles virus, called AIK strain, developed by Makino and his colleagues at the Kitasato Institute, Tokyo, was adapted to human diploid cells (HDC), MRC-5. In a field trial it was found that this strain initiates a low rate of clinical reactions and 100% seroconversion in vaccines. An attenuated strain of rubella virus, called Takahashi strain, isolated by Shishido at the National Institute of Health, Japan, was also adapted to HDC, MRC-5. Brief details of production of an experimental rubella vaccine are given. Up to 20 harvests of virus were made from each culture without any apparent alteration of diploid cells.


Clinical responses to T(n)BP-disrupted HDCS (WI-38) rabies vaccine. Study of 10 batches of an antirabies vaccine made from purified, concentrated subunits (Pitman-Moore strain adapted to Wistar HDCS). One single dose of vaccine is insufficient; three or more doses induce high antibody levels. Among more than 2000 vaccines secondary reactions were rare and generally mild and transient. All the individuals vaccinated post-exposure remained without rabic symptoms. The vaccine was also particularly efficacious for booster doses.


The nutrient requirements of MRC-5 human diploid cells. Nutrients were assayed by their effect on maximum cell yield (maximum cell population less inoculum) of MRC-5 cells previously maintained in Eagle's basal medium with 10% (v/v) serum, trypsinised, centrifuged and washed. When nonlimiting amounts of iron, methylcellulose and a 68-component supplement were included in our defined medium, cell yields obtained were equivalent to those obtained with 2 to 3% whole serum. Growth then became limited by serum growth factors which, when serum was fractionated by the low temperature ethanol procedure, appeared to precipitate with the alpha-globulins, although the distribution of activity varied from batch to batch of serum. Column chromatography (DEAE and concanavalin A-Sepharose) of serum resulted in much (20 to 45%) loss of growth factor activity during exhaustive dialysis or Sephadex G-25 desalting suggesting that the growth factor may be a diffusible molecule bound in serum to a large protein carrier.


[Lipid and phospholipid content of canine liver tissue after portacaval anastomosis with or without additional arterialization of the intrahepatic portal vein]. The concentration of phospholipids and total lipids was determined 4 weeks after a portocaval shunt (PCS) in liver tissue of adult mongrel dogs. The concentration of total lipids increased from 33.5 +/- 3.6 to 71.2 +/- 6.9 mg/g ww, whereas the concentration of phospholipids declined from 26.1 +/- 3.1 to 19.8 +/- 7.8 mg/g ww. These changes are not observed when, in addition to the PCS, a pressure-adapted arterialization of the liver is established. They are therfore caused by the decreased blood supply to the liver after PCS alone.


[Etiology of benign papillary stenoses]. In domestic pigs repeated applications of gastrointestinal hormones (pancreozymin, secretin) as well as cholecystectomy lead to histologic transformation of the epithelium in the area of the papilla of Vater and to inconstant pressure changes in the common duct.


[Myocardial blood flow and oxygen consumption in the fibrillating and empty-beating heart]. Myocardial flow and oxygen consumption are reduced during cardiopulmonary bypass. In ventricular fibrillation both flow and O2 consumption are higher than in the empty beating heart; after the fibrillation flow remains elevated although O2 consumption decreases. Aortic pressure is the major determinant of the myocardial flow rate, especially in hemodilution.


[Studies on the local motility and blood circulation of the heart muscle during and after long-term coronary strangulation]. In ten young pigs a severe prolonged and critical stenosis of a major coronary artery was produced under control of an electromagnetic flowmeter. With stepwise constriction flow could be reduced to 55% of control with only minor hemodynamic changes. Local myocardial segment shortening was depressed to approximately 30% of control values. Hypokinesis was partially reversible within the first 135 min after reperfusion and had disappeared 24 h later. Computerized perfusion scintigraphy with radioactive microspheres gives a reliable approximation of the degree of myocardial blood flow reduction.


[Myocardial blood flow and ventricular function in dependence on the size of myocardial infarct]. In eight dogs three branches of the left anterior descending coronary artery were occluded by successive ligations. Each time coronary flow reserve was measured by injecting dipyridamole (0.4 mg.kg-1). After an infarction of 13% of the left ventricle there was a significant decrease of Vmax and dp/dtmax (p less than 0.05). Measurements of regional myocardial blood flow detected an infarction of 5% of the left ventricle, whereas the total myocardial blood flow was reduced significantly when 17% of the left ventricle was infarcted.


[Animal experiments with a new intracardial pacemaker electrode]. In order to reduce the rate of dislocation of intracardiac pacemaker electrodes, a new electrode was developed. The tip of this new electrode is helical and can be fixed between the trabecles of the right ventricle by clockwise rotation. Since the tip of this new electrode has no sharp hooks the myocard cannot be damaged by fixation.


[Frequency-optimal pacing in chronic pacemaker therapy]. Hemodynamic studies were performed in 15 pacemaker patients at rest and during exercise by thermodilution technique and impedance cardiography. Particularly in myocardial failure, individual optimal heart rates were observed, ranging from 90 to 120/min. Mean increase of cardiac output at optimal pacing rate was 1.31/min against stimulation at 70/min. Impedance cardiography showed high correlation to thermodilution technique.


[Criteria for the choice of a membrane oxygenator in long-term oxygenation]. Five different membrane oxygenator devices were tested in dogs. The following criteria were compared: operating reliability, gas exchange rates, and changes of the mean erythrocyte volume.


[Study of turbulence in the normal and stenotic vessel]. Velocity measurements were performed at the test bench, in dogs and in patients with pulsed ultrasound. A new zero crossing counter was used to measure the different frequencies of the doppler spectrum in real time. The ratio of the standard deviation of the radial mean velocity to the radial mean velocity expressed as a percentage proved to be a useful turbulence index to describe stability of flow.


[Significance of various implantate localizations of Sparks prostheses, experimental studies in rats]. Our investigations show that Sparks prostheses after subcutaneous implantation are suitable for vascular grafting. At the end of the organization period the connective tissue becomes strong, and after the third and fourth weeks collagenous and elastic fibers can be seen. Ten weeks after s.c. implantation, collagenous fibers predominate. After this the Sparks prostheses can be used as a vascular graft. Intraperitoneal implantation, however, shows a histologically different picture with characteristic findings: only fat cells can be observed, a strong granulation tissue with elastic and collagenous fibers is not present. After intraperitoneal implantation Sparks prostheses are therefore unsuitable for vascular grafts.


[Morphological and functional changes in the closing sphincter of the lower esophagus after experimentally-induced hiatal hernia]. Report of an experimental model of axial hiatal hernia in dogs, always combined with reflux (roentgenologic control). Using a new method of pressure measurement, the authors succeeded in proving the distention of the esophageal "sphincter". Morphologic investigations demonstrated, that in hernia the muscle fiber is no longer an apolar helical fiber, but runs nearly horizontally. The reduced susceptibility to pentagastrin is caused by diminished tension of the muscle fiber. The distal esophageal closing mechanism consequently seems to be a function of the whole organ and not of a hormonally regulated sphincter.


[Influence of somatostatin (GIF) and human gastrin I on the lower esophageal sphincter]. The influence of gastrin and somatostatin on the lower esophageal sphincter was investigated in 10 metabolically healthy volunteers and one patient with Zollinger-Ellison syndrome. It could be shown that only unphysiologically high concentrations of gastrin produced a rise in pressure in the lower esophageal sphincter, while somatostatin has neither an effect on the lower esophageal sphincter pressure, nor is it able to inhibit the pharmacologic effect of exogeneous gastrin administration. The results emphasize that gastrin and somatostatin have no influence on the tone of the lower esophageal sphincter.


[Manometric studies on the influence of selective proximal vagotomy on the lower esophageal sphincter]. Selective proximal vagotomy (SPV) decreases the LES pressure (resting pressure and pentagastrin-stimulated pressure), significantly 6 months postoperatively without achieving LES insufficiency by clinical means. Immediately after stimulation LES pressure is identical, compared to preoperative measurements. Concentration of serum gastrin is not a major determinant of LES tone in humans.


[Myoelectrical changes of activity of the Vater's ampulla after various forms of vagotomy in the dog]. The effects of varying the extent of vagotomy on the myoelectrical activity of the sphincter of Oddi have been successfully studied in 12 dogs undergoing either truncal, selective, or highly selective vagotomy. Both the amplitude and the shape of the single action potentials as well as the interval change in the electrical activity in the sphincter of Oddi in relation to the extent of the vagal denervation. No significant change of frequency and amplitude of the myoelectrical activity occurred after highly selective vagotomy which proves to be the best method.


[Reproducibility and specificity of insulin-injection and insulin-infusion tests in the examination of complete vagotomy]. The reproducibility of insulin injection tests, the comparison of insulin injection and insulin infusion tests and the specificity of the insulin injection tests were investigated in 74 duodenal ulcer patients. New failures of the insulin test were detected. The criterion of BACHRACH produced more positive "insulin tests" after injection of sodium chloride than after insulin itself. Therefore it is recommended that in single cases (recurrent ulcer) insulin injection tests (HOLLANDER criterion) should be repeated and that a sodium chloride test should be performed.


Effects of vagotomy on the catecholamine-containing cells in the gastric mucosa of the rat: an electron microscopic study. The ECL cells in the fundic mucosa from five different groups of fasted rats were examined by means of electron microscopy; in the control animals, the majority of the secretory granule of the ECL cells contained electron-dense material. Previous studies in our laboratory indicate that this material probably represents a catecholamine. In the second and third groups, in which truncal vagotomy plus pyloroplasty was performed, the secretory granules were depleted of their content. In the fourth group in which vagotomized animals were treated with iproniazid and L-dopa, the mature secretory granules were depleted but formation of new granules was apparent. In the fifth group, in which pyloroplasty alone had been performed, the content of the granules was the same as in the control group. It was concluded that the endocrine function of the ECL cells is under vagal control and that vagotomy causes release of catecholamines from these cells.


[Experimental studies of the effects of gastrin, neostigmine and prostaglandin on the motility of the trunculary vagotomized stomach]. The working effect of Gastrin, neostigmine and prostaglandin in regard to the emptying of the stomach was tested on 31 dogs that had undergone a truncular vagotomy. Gastrin and neostigmine were proved to increase the motility at the stomach pylorus but was not able to bring about a coordinated emptying pattern. Prostaglandin shows different effects on the emptying reflex of the stomach. PGF 2 alpha increases the motility on the measuring marks, but at different time intervals. Because of this a coordinated motility is made possible.


[Studies on the hormonal regulation of the esophago-gastric and gastro-duodenal high-pressure zone after vagotomy and resection of the antrum]. Studies on gastric emptying after antrectomy and vagotomy with gastroduodenostomy show that the gastric remnant empties in the same way as the intact stomach by hormonal control. If gastrointestinal passage after gastric resection is restored by gastrojejunostomy no endocrine regulation can be found.