Quantitative autoradiographic light- and electron microscopic studies on the retinohypothalamic connections in the rat.

Light microscopic autoradiography performed subsequent to intraocular injection of 3H-leucine revealed silver grains (SG) above axons of the optic tract which could be followed into the ventral and caudal portion of the suprachiasmatic nuclei (SCN) and above the contralateral anterior hypothalamic nucleus (AHN). By high resolution photometric measurement and computer processing the labelled areas were analysed, thus yielding statistical data of the relative grain distribution. The highest SG density was found in the ventrolateral part of both SCN (SCvl), confirming earlier reports concerning retinohypothalamic connections. That area exhibiting a cytoarchitecture different from the remaining nucleus was traversed, however, by numerous labelled axons. In the caudal part of both SCN a specific projection field of retinal fibres could be located. Here, almost no traversing fibres contribute to the rather circumscribed marked area. In the ventral part of the contralateral AHN, diffuse labelling well above background levels could be observed. Distinction between bypassing and terminating fibres within the SCvl could not be made using light microscopy. Analysis of SG distribution of the SCvl with electron microscopic autoradiography revealed a specific localization of SG within presynaptic terminals containing clear vesicles and pale mitochondria.


Ultrastructural study of embryonic and post-hatching development in the pineal organ of the chicken (brown leghorn, gallus demosticus).

The pineal organ of the chicken was investigated electron microscopically during embryonic and post-hatiching development with special regard to photosensory and secretory features. Throughout the developmental period both pinealocytes and supporting cells, of which the pineal parenchyma is composed, were rich in ribosomes, granular endoplasmic reticulum and mitochondria, but lacked agranular endoplasmic reticulum. The outer segments of pinealocytes barely showed formation of lamellar structures (disks) at the 17th and 21st day of incubation. Before and after hatching the follicular lumen was ofter filled with amorphous material presumed to be derived from outer or inner segments. By 15 days after hatching thw whorl-like structures were occasionally connected to bulbous outer segments, and their relation appeared similar to that of the adult. Mitochondria disappeared from the inner segments after 21 days of incubation. Dense core vesicles (about 80-120 nm in diameter), regarded as secretory granules, appeared first at the 10th day of incubation in the supranuclear region of the pinealocyte. With the extending of basal processes the dense core vesicles gradually migrated into these processes, attained maximum number one month after hatching and increased further in the adult; they are located both around the Golgi apparatus and in the basal process. These results provide evidence that secretory activity is maintained from embryonic stages to adulthood.


Substructure of solitary cilia in mouse kidney.

Recent scanning electron microscopic studies confirm the presence of solitary cilia on most epithelial cells along the mammalian nephron and collecting ducts. By transmission electron microscopy we have found that the axonemata of such cilia consist of a maximal number of 9 doublet and no singlet filaments. 10% of the cross-sectioned cilia contain 9 doublets arranged in peripheral ring (9 + 0 pattern). 30% of the cross-sections contain 8 or 7 doublets  in peripheral ring and 1 or 2 doublets in the central region (8 + 1 and 7 + 2 patterns). Serial sections and goniometer tilt reveal the central doublets to originate as dislodged peripheral doublets. 60% of the sectioned cilia contain filament numbers between 8 and 4. In patterns of 5 and 4 filaments single microtubules predominate. The functional significance of these atypical cilia is discussed.


Synaptic organization of the cabbage looper moth ocellus.

Chemical and electronic synapses are present in the ocellar synaptic region of the moth, Trichoplusia ni. The chemical synapses all appear to be of "conventional" type. Four different chemical synaptic contacts were observed: Receptor cell axons presynaptic to receptor cell axons, receptor cell axons presynaptic to 1st order interneurons, 1st order interneurons presynaptic to receptor cell axons, and 1st order interneurons presynaptic to 1st order interneurons. Two different types of contact made by electronic synapes were observed: Contacts between receptor cell axons and 1st order interneurons, and contacts between 1st order interneurons. The significance of this synaptic arrangement for the generation of "on" and "off" responses in the 1st order interneurons is discussed.


Haemocyanin synthesis in pore cells of the terrestrial snail Helix aspersa.

Ultrastructural evidence is presented that the pore cells of the interrestrial snail Helix aspersa are involved in the production and secretion of haemocyanin.


Renewal of mouse gastric mucous cells following fast neutron irradiation. An ultrastructural and carbohydrate histochemical study.

Mouse gastric mucosa was studied ultrastructurally and histochemically after exposure to fast neutron irradiation, the number of cells per gastric gland was decreased and the glands were shorter. At day 9, several glands showed a dilated lumen lined by flattened cells. Between days 9 and 16, some of the glands disappeared. Parietal and chief cells disappeared from the remaining glands. At the same time, restoration of the mucosa started. At day 6, proliferative cells were scattered along the isthmus. As in controls, the isthmus contained a few undifferentiated cells many differentiating surface mucous cells (SMC) with developing rough endoplasmic reticulum and silver proteinate-reactive Golgi elements and small secretory granules. At day 9, numerous proliferative cells were clustered in foci. Almost all these cells contained silver proteinate-reactive Golgi elements, granules and vesicles. Most of them were SMC, others mucous neck cells (MNC) or intermediates. At day 16, proliferative foci were larger and consisted of differentiated mucous cells. Regenerated foveolae and glands consisted of large SMC and MNC and a few fibrillovesicular cells. In conclusion, proliferative activity is confined to undifferentiated cells and differentiating mucous cells, which identifies them as the progenitors of the other gastric cell types.


Fine structure of the ultimobranchial cysts in the thyroid of the adult guinea pig.

The ultimobranchial cysts in the thyroid of the adult guinea pig are identified by a cytochemical method. The ultimobranchial tissue has the shape of an irregular cyst, with non-specific esterase activity that is resistent to HgCl2 inhibition. The TEM reveals five different types of epithelial cell in the cyst wall: 1. cells with deeply invaginated nuclei and of varying shape, from flat to cylindrical but most of them cuboidal. 2. Mucous cells that are tall and similar to goblet cells. 3. Tall cells with big granules that have a dense core. 4. Ciliated cells similar to those in the respiratory tract. 5. C-cells crowded with the small dense granules typical for the cell type. The cyst is enveloped by rather coarse collagen fibers and many wide sinusoids.


An ultrastruct study of the innervation of the musculature of the pond snail Lymnaea stagnalis (L.) with reference to peripheral neurosecretion.

The ultrastructure of nerve endings in the musculature of Lymnaea stagnalis was studied. Seventeen different types of axon ending were distinguished according to the size and morphology of the granules or vesicles they contain. Nine types of axon endings form neuromuscular synapses. Some of these types also form axo-somatic synapses on peripheral neurones. One axon may innervate several muscle cells. Furthermore more than one type of axon may innervate one muscle cell. One type of axon ending forms axo-axonic synapses on the presynaptic part of neuromuscular junctions. In the connective tissue near muscle cells seven types of free axon endings were found. These seem to be peripheral neurosecretory endings. Some of these are probably derived from known types of neurosecretory cells in the central nervous system, whereas others appear to originate from peripheral neuronal perikarya. Body wall muscles appear to be innervated by neuromusculatur synapses, whereas in the visceral musculature both neuromuscular junctions and free axon endings are found.


Unit gravity sedimentation separation of cells comprising the caput epididymidis of the rat.

Cells from the rat caput epididymidis were separated by unit gravity sedimentation. Purest 12-ml fractions contained 88-95% basal cells or 64-76% principal cells. Ultrastructure of separated cells was similar to that of cells in intact tissue. Viability of separated cells was excellent as determined by dye exclusion tests and cellular ATP content. By combining fractions pools containing 4.0 +/- 0.9 X 10(6) cells (86 +/- 8% basal cells) and 1.4 +/- 0.4 X 10(6) cells (56 +/- 7% principal cells) were obtained. Thus, studies on the function of basal and principal cells from the rat caput epididymidis should be possible.


Cellular and subcellular localization of 3h-diethylstilboestrol in the central nervous system.

The cellular and subcellular localization of radioactivity in the brain of immature female rats was determined by dry-mount autoradiography 2 h after iv injection of 1.0 microgram of (monethyl-3H) diethylstilboestrol per 100 g body weight. A specific topographic pattern of nuclear concentration of the synthetic oestrogen was obtained similar to that for 3H-oestradiol-17 beta in specific neurons of the basal hypothalamus, preoptic region and amygdala. In competition experiments, the nuclear concentration of radioactivity in all areas studied was inhibited by unlabeled oestradiol, while unlabeled testosterone had no effect. These data suggest that although oestradiol can bind to androgen receptors, the oestrogen receptor itself can account for the localization seen after the injection of 3H-oestradiol.


The fine structure of testicular interstitial cells in the adult golden hamster with special reference to seasonal changes.

The fine structure of the testicular interstitium was studied in normal adult golden hamsters sacrificed in the reproductive season (spring and summer) and in the winter. The Leydig cells in the reproductively active testes contain abundant endoplasmic reticulum (ER) and numerous mitochondria. The ER occurs in the form of flattened cisternae and tubules, the former prevailing. The cisternae are extremely extensive and are partly granular and partly agranular, their ends being continuous with the tubluar reticulum. Mitochondria intervening between the cisternae are closely associated with the agranular portions of the latter. Adjacent to the Golgi complex and continuous with the centrosome a unique filamentous body with a dense laminar core is often observed. In the regressive testes, the Leydig cells show a great reduction of cytoplasmic volume and a remarkable decline of the organelles, especially agranular tubules. The possible functional significance of the tubular and cisternal ER with the associated mitochondria is discussed in relation to the biosynthesis of androgens. Macrophages appear to constitute another important population of the interstitial cell clusters.


The development and ultrastructure of previously dissociated foetal human cerebral cortical cells in vitro.

Cells from foetal human cerebral cortex were mechanically dissociated and subsequently maintained in vitro for periods ranging between three and twenty-eight days. The ultrastructure of these cells at different stages of their development in culture was extensively examined. Nuclear and cytoplasmic features were extremely variable and a wide range of cell types was evidently represented. Of the three principal cell types found i.e. neurons, neuroglia and mesenchymal cells, only a minority of cells was classified with confidence, particularly during the first two weeks in culture. Extensive intercellular junctions of the adhaerens variety, common after 14 days in vitro were present at an earlier stage of development than synaptic profiles. First indications of synapse formation were observed after 21 days in vitro and after 24 days presynaptic sites filled with synaptic vesicles and with well defined presynaptic and postsynaptic thickenings were found. The significance of some of the features observed are both considered and discussed.


Larval adhesive organs and metamorphosis in ascidians. I. Fine structure of the everting papillae of Distaplia occidentalis.

The larava of Distaplia occidentalis bears three cup-shaped adhesive papillae, each with a prominenta axial protrusion, At the onset of metamorphosis these organs rapidly evert through fenestrations in the cuticular layers of tunic exposing hyaline caps of adhesive. Additional adhesive material is secreted from collocytes during eversion. The stickiness of the papillae facilitates attachment to a variety of substrates. Each papilla is composed of more than 900 cells; six different types were identified. The wall of the cup contains about 260 myoepithelial cells with long attenuated processes. These extend from the rim of the cup to the base in the parietal (inner) layer. The apices of the myoepithelial cells are held in place by 11 pairs of specialized anchor cells bearing long bulbous microvilli. When the myoepithelial cells contract they force the axial protrusion forward and transform the papilla into a hyperboloidal configuration. The papilla is innervated by small motor fibers, but sensory fibers were not detected. The adhesive papillae of Distaplia are discussed in relationship to nine other recognizable types of papillae in the ascidians.


Fine structure of the olfactory epithelium in the goldfish, Carassius auratus. A study of retrograde degeneration.

The fine structure of the goldfish olfactory epithelium was studied by transmission and scanning electron microscopy. Six different cell types were distinguished. Identification of the olfactory receptor cell was accomplished by use of retrograde degeneration studies. Two morphologically distinct types of olfactory receptor cells were identified: one type bears radially oriented cilia (Type I cell); the other type bears microvilli (Type II cell). The other four cell types were not identifiable as olfactory receptor cells: they are ciliated cells (Type III), rod-shaped cells (Type IV), supporting cells (Type V), and basal cells (Type VI).


Effects of blinding on the ultrastructure of mouse pinealocytes with particular emphasis on the dense-cored vesicles.

The mammalian pineal is thought to produce an antigonadotropic principle under conditions of reduced photoperiod, constant darkness or blinding by optic enucleation. A number of previous studies on mammalina pineals have suggested that the dense-corde vesicles present in pinealocytes may represent morphological evidence of secretory activity. In the present study the ultrastructure of pinealocytes was studied in adult Charles River CD-1 mice blinded by optical enucleation. By one month following optic enucleation the mean number of dense-corde vesicles in the cytoplasm of pinealocytes adjacent to pericapillary spaces had significantly decreased by 55% when compared with intact controls, and remained at this low level at two months and six months. A relative increase in the proportion of large agranular vesicles and an increased number of large, irregular vacuoles was observed also in the pinealocytic polar processes of blinded mice. When compared to control mice the pinealocytic Golgi regions appeared to be hypertrophied in blinded mice. The apparent stimulation of pinealocytic organelles coupled with the observed decrease in dense-corde vesicles suggest an increased synthesis and release of secretory product.


Glycoprotein secretion in the mouse submandibular gland as revealed by radioautography after L-3H-fucose injection.

Glycoprotein secretion in the mouse submandibular gland was investigated by light microscope radioautography of semi-thin sections after the administration of L-3H-fucose. The incorporation of the precursor in the acini was negligible. 3H-fucose was taken up in the paranuclear region of the cells lining the intercalated, secretory, striated and excretory ducts. This labeling pattern was interpredted as addition of the precursor to glycoproteins within the Golgi apparatus. Incoropration in the intercalated duct was restricted to the cells with fine cytoplasmic granules. The glycoproteins synthesized by the intercalated and secretory ducts were transported to the saliva by the secretion granules. It is assumed that the glycoproteins synthesized in the striated and excretory ducts are plasma membrane glycoproteins which seem to renew continuously. Quantitation of the radioautographs supplied data concerning the incorporation of 3H-fucose into newly synthesized glycoproteins as well as the renewal of the labeled macromolecules in each duct.


A scanning electron microscopic survey of the brain ventricular system of the female armadillo.

The scanning electron microscope was used to survey the brain ventricular system of the female armadille (Dasypus novemcinctus) with emphasis on the third ventricle. The walls of the lateral ventricles, aqueduct, and fourth ventricle are covered by long cilia. In the lateral ventricle, the cilia are arranged in groups; but in the aqueduct and fourth ventricle, they are evenly placed over the cellular surfaces. The ependymal cells of the third ventricle are densely ciliated except for the organum vasculosum and infundibular recess. The non-ciliated luminal surface of these areas has a pebblestone appearance punctuated by numerous microvilli and two types of supraependymal cells.


Special dendritic and axonal endings formed by the cerebrospinal fluid contacting neurons of the spinal cord.

The cerebrospinal fluid (CSF) contacting neurons have a dendritic process which protrudes into the central canal, and is provided with one long kinocilium and many shorter stereocilia (about 80 in the turtle) as revealed by scanning electron mecroscopy. The shape, number and arrangement of the cilia are similar to those of known receptor endings. The silver impregnated axons of these cells converge to a paired centrosuperficial tract forming terminal enlargements at the ventrolateral surface of the spinal cord. Lying among glial endfeet these terminals are ultrastructurally similar to those present in known neurosecretory areas. The nerve endings are attached to the basal lamina, and they comprise many synaptic vesicles (200 to 400 A in diameter), as well as granular vesicles of different sizes (diameter 600 to 1800 A). The axons may lie within finger-like protrusions on the surface of the spinal cord, or they may terminate around vesseles. Morphological evidence suggests that these nerve terminals and the corresponding CSF contacting perikarya represent a spinal neurosecretory system possibly influenced by information taken up by its special dendrites protruding into the inner CSF space.


A new cell type in the taste buds of anurans. A scanning and transmission electron microscopic study.

A hitherto undescribed cell type within the fungiform papillae of the tongue of the toad, Bufo bufo (L.) and the taste-disks of the soft palate of Bombina variegata L. was identified by means of scanning and transmission electron microscopy. This cell type is characterized by an apical protrusion carrying numerous microvilli. Bundles of filaments are present in the cytoplasm of the protrusion. Vesicles with electron lucent content and microtubules are present thoughout the cytoplasm of the cell.


Immunocytochemical investigation of the hypothalamo-neurohypophysial system in birds.

The results of an immunohistochemical investigation of the hypothalamo-neurohypophysial system in several species of birds have shown that: (1) mesotocin and vasotocin are synthesized in separate neurons; (2) in all species investigated the distribution of mesotocinergic and vasotocinergic perikarya follows a common pattern; (3) the external zone of the avian anterior median eminence contains exclusively vasotocinergic nerve fibers, originating in supraoptic and ventral paraventricular regions; (4) the distribution of immunoreactive elements in the neural lobe shows a definite species-dependent pattern.


Sympathetic innervation of the carotid bifurcation in the rabbit and cat: blood vessels, carotid body and carotid sinus. A fluorescence and electron microscopic study.

Two postganglionic branches of the superior cervical ganglion enter the area of the carotid bifurcation in the rabbit and the cat. The common and external carotid arteries receive a rich adrenergic nerve supply, which can be demonstrated by fluorophores of biogenic amines appearing after formaldehyde treatment. The internal carotid artery is only sparsely innervated; however, it shows a dense sympathetic supply at the site of pressor receptors. Following removal of the superior cervical ganglion, a total loss of fluorescent adrenergic nerves occurs and degeneration of nerve endings possessing dense core vesicles is conspicuous. These nerve terminals are situated mainly subendothelially in the carotid body sinusoids; they only rarely terminate on type I cells.


An in vitro morphological study of the mouse visceral yolk sac and possible yolk sac immunocyte precursors.

Mouse visceral yolk sac has been organ cultured from 9 days of gestation, a time prior to the thymus being lymphoid, until 12 days of gestation, a time after which the thymus is lymphoid. During the culture period the endodermal epithelial cells survived well, erythropoiesis diminished, endothelial-lined cavities formed in the mesodermal mass, and cells developed which have been classified as large, medium and small immunocyte precursors. The cytoplasm of the immunocyte precursors contains polysomes, spherical mitochondria, a few profiles of rough endoplasmic reticulum, occasional granules and a large Golgi complex. This study offers morphological support for the yolk sac origin of immunocyte precursors in the mouse which may seed the thymus and liver.


Electron microscopical study on the development of the nerve supply of the pituitary pars intermedia of the mouse.

The development of the nerve supply of the pituitary pars intermedia (PI) of C3H mice was studied by electron microscopy. Nerve fibres and terminal structures, most probably adrenergic, first appear in the newborn. The adult innervation pattern is achieved by the end of the first postnatal week. In the adult animal two types of nerve terminals were distinguished; type A (peptidergic or neurosecretory) and type B (adrenergic). The peptidergic fibres were scarce and exhibited no synapse-like contacts. It is suggested that they are of secondary importance in a direct nervous hypothalamic control of PI function. Type B terminals were found throughout the PI. They formed synapse-like contacts with the glandular cells, indicating that the primary innervation is exerted by adrenergic neurons. An autonomous differentiation of the glandular cells and in the adult a combined direct nervous and neurohumoral control of PI function is suggested.


An unusual organelle in the pineal gland of the rat.

An electron microscopic survey of pinealocytes from normal rats revealed a highly organized arrangement of cytoplasmic tubules. Such tubules had been previously observed in normal rats (Lin, 1967) and in rats after melatonin administration or two weeks exposure to darkness (Freire and Cardinali, 1975). In a later publication the presence of the tubules was attributed to experimental manipulation resulting in infertility (Gusek, 1976). The present study resolves the discrepancy in the literature by establishing that the tubular organelle does indeed occur in untreated male rats, but rather rarely.


Tight junctions of oligodendrocytes.

Freeze-fracture replicas of the rat corpus callosum revealed prominent junctional strands in fractured cell membranes of the somata of oligodendrocytes. The junctional strands were characterized by an elaborate system of straight or slightly undulating rows of linear aggregates of particles or ridges in the P face and furrows in the E face.


The collicular recess organ: evidence for structural and secretory specialization of the ventricular lining in the collicular recess.

The collicular recess organ and adjacent portions of the collicular recess were studied by light microscopy, scanning electron microscopy and transmission electron microscopy. In the collicular recess, the ventricular wall contains folds and is well vascularized. The adluminal ependymal cells generally bear kinocilia and microvilli on their ventricular surface. Among the cilia, many secretory droplets, some axons, and few supraependymal cells are seen. Various stages of apocrine ependymosecretion are observed. In addition to tanycytes, coelocytes are found scattered throughout the ependymal lining of the collicular recess. Coelocytes, characterized by lumina containing cilia and a few microvilli, are accumulated in ependymal and hypependymal positions of the collicular recess organ at the roof of the collicular recess.


The fine structure of the compound eyes of mysids (crustacea: mysidacea).

The ultrastructure of the compound eyes of five species of mysids (Crustacea: Mysidacea), Praunus flexuosus, Siriella norvegica, Mysidopsis gibbosa, Neomysis integer and Erythrops serrata, is described. The ommatidia are constructed on a common plan, but there are considerable differences in detail. Common features include the arrangement of the cornea, crystalline cone and the basement membrane. The number of retinular cells differ: in Neomysis and Erythrops there are seven, whereas in the other species there are eight, the eighth cell forming a distal rhabdom, which consequently is lacking in the ommatidia of Neomysis and Erythrops. Another difference is the epirhabdom, which is lacking in Erythrops, but present in the other species. The epirhabdom is an extracellular structure, probably serving as a dioptric element. The pigment arrangement is similar in the first four species. The pigment shield consists of the distal pigment, distal reflecting pigment, proximal pigment (in the retinular cells) and the proximal reflecting pigment. The distal and proximal pigments are dark screening pigments. In addition to these, there are basal red pigment cells, which are mainly located below the basement membrane. In Erythrops there are three kinds of pigment cells: distal pigment cells, distal reflecting pigment cells and basal red pigment cells. Besides the basal red pigment cells, the distal pigment cells contain red pigment granules.


Neurosecretion. XVI. Protrusions of bounding membranes of neurosecretory granules.

Protrusions of bounding membranes of neurosecretory granules, comparable to those demonstrated by Castel (1977) in the mammalian neurohypophysis, were observed under various experimental conditions in the corpora cardiaca of the insects Leucophaea maderae and Periplaneta americana. Electrical stimulation in vitro of the nervus corporis cardiaci I, which elicited a marked rise in the amount of neurohormone discharged, as determined by bioassay, also yielded a significantly larger number of membrane protrusions than were observed in unstimulated controls. However, no comparable response was obtained in glands subjected to stimulation of hormone release by exposure to serotonin or high potassium concentrations. On the other hand, membrane protrusions were numerous under certain conditions not expected to stimulate neurohormone release, i.e., in tissue exposed to a zinc iodide mixture without prior fixation. The present results support the conclusion drawn by Castel that these configurations appear to be related to the process by which neurosecretory material is discharged. Too transient to be much in evidence under physiological condition, they become more prominent not only after appropriate acceleration of the rate of release, but also when such membrane arrangements are "frozen" by procedures that interfere with the regular milieu.


Testicular involution following optic enucleation. An ultrastructural and cytochemical study.

The testes of adult male Syrian hamsters underwent involution within six weeks after optic enucleation. The diameter of the seminiferous tubules was 39% less than controls. Sertoli cells, spermatogonia, and primary spermatocytes were still present, but all steps of spermatids were completely absent from the involuted testes. Lipid droplets filled the Sertoli cell cytoplasm and often encroached upon the nucleus. Sertoli cells had sparse mitochondria and smooth endoplasmic reticulum, but Golgi cisternae were abundant. Typical Sertoli-Sertoli junctions attached contiguous Sertoli cells. With lanthanum tracers it was demonstrated that these junctions were impenetrable; therefore, the blood-testis barrier was deemed intact. Irregularly shaped protrusions often arose from the peritubular tissue and extended inward toward the seminiferous epithelium, often displacing the cytoplasm of the Sertoli cells and spermatogonia. The core of these protrusions consisted of irregular extensions of myoid cell cytoplasm surrounded by the myoid cells' basal lamina. External to the myoid cell basal lamina were bundles of collagen filaments with the basal lamina of the seminiferous epithelium forming the outermost layer of these protrusions. The apices of the Sertoli cells gave rise to numerous leaf-like processes that extended into and obliterated the lumen of the tubules. The Sertoli cell basal cytoplasm often contained phagocytized degenerating germ cells that appeared to give rise to the lipid droplets that filled the Sertoli cell cytoplasm. Acid phosphatase rich lysosome-like organelles were seen fusing with the degenerating germ cells and lipid droplets. The degenerating germ cells also were shown to contain acid phosphatase activity.


The eyes of mesopelagic crustaceans: I. Gennadas sp. (penaeidae).

The eye of the deep-sea penaeid shrimp Gennadas consists of approximately 700 square ommatidia with a side length of 15 micrometer. It is hemispherical in shape and is located at the end of a 1.5 mm long eye stalk. The cornea is extremely thin, but the crystalline cone is well-developed. A clear zone between dioptric structures and the rhabdom layer is absent. A few pigment granules are found within the basement membrane; otherwise they, too, are absent from the eye of Gennadas. The rhabdom is massive and occupies 50% of the eye. It consists of orthogonally oriented microvilli (the latter measuring 0.07 micrometer in diameter) and is 75 micrometer long. In cross sections adjacent rhabdoms, all approximately 8 micrometer in diameter, form an almost continuous sheet and leave little space for retinula cell cytoplasm. In spite of a one h exposure to light, rhabdom microvilli show no disintegration or disruption of membranes. Vesicles of various kinds, however, are present in all seven retinula cells near the basement membrane. Bundles of seven axons penetrate the basement membrane. On their way to the lamina they often combine and form larger aggregations.


Ultrastructure of rat ovarian interstitial gland cells during pregnancy.

The fine structure of the interstitial gland of the rat ovary was studied at estrus and on Days 4, 6, 10, 14 and 18 of pregnancy. At estrus, ovarian interstitial cells have small nuceli with dense irregular clumps of heterochromatin. Mitochondria are small and rod-shaped and have predominantely lamellar cristae. Numerous osmiophilic lipid droplets are present. At Days 4 and 6, nuclear heterochromatin is reduced, and nucleoli are larger and complex. Mitochondria are enlarged and often bizarre-shaped and have tubular cristae. Golgi and smooth endoplasmic reticulum are more conspicuous. At Day 10, prominent ultrastructural features include nuclei with conspicuous heterochromatin, smaller mitochondria with both lamellar and tubular cristae, numerous ribosomes and lipid droplets with decreased osmiophilia. At Days 14 and 18, nuclei have increased heterochromatin, mitochondria are small and have lamellated cristae and an increase in the size and number of lipid droplets occurs. These observations suggest that steroidogenic activity of interstitial cells is highest during the first half of pregnancy and regresses during the last half. It is suggested that the interstitial gland is an important ovarian source of pregnancy hormone(s) during the first half of gestation and that LH may modulate steroidogenic activity is this ovarian component.


Changes in nuclear DNA and RNA during epidermal keratinization.

The distribution of nucleic acids within nuclei of epidermal cells in skin from guinea-pig ear was investigated using an indirect enzyme digestion technique to observe both DNA and RNA, and a direct Schiff-Thallium reaction technique, to observe DNA alone. Similar results were obtained by both methods. The distribution of DNA and RNA change gradually in nuclei as epidermal cells differentiate. DNA in cells of the lower strata is localized in essentially the same areas in which electron-opaque components are seen by conventional electron microscopy. With the cytochemical treatments, however, we found that DNA is not present in all electron-opaque areas of nuclei in superficial granular cells. RNA is present in the nucleoli of cells in all layers, but its density is also lower in the upper granular cells. We postulate that nucleic acids in nuclei of granular cells gradually decrease and that the space is filled with newly synthesized electron-dense protein, as part of the differentiation process.


The migration of osteoblasts.

The endocranial matrix surfaces of parietal bones of 2-week old Albino Wistar rats were partly denuded of osteoblasts and then cultured for various periods up to 24 h, in control or PTE-enriched medium. They were examined by scanning electron microscopy and evidence for cell locomotion was found. Osteoblasts traversed the denuded bone surface and cut edges of bone in either medium, and cells also migrated out from vascular channels. Glass spicules were placed on the otherwise undisturbed osteoblast layer in similar organ cultures for 2, 3 or 5 days. Osteoblasts migrated from the bone to populate the glass, negotiating any angle. The cells in PTE-enriched media were always aligned parallel to one another and elongated, tended to align with the edges of the glass and, in time, formed a substrate of aligned fibrils whose axes were parallel to those of the cells. Osteoblasts in control medium on glass showed variable degrees of alignment and elongation and were less influenced by edges of the glass. Non-locomotory, nearly equidiametrical cells on glass in 5d control cultures had formed a substrate of randomly oriented fibrils. Migrating osteoblasts on bone matrix did not have leading edge ruffles; isolated, migrating ones on glass did.


Arrangement of smooth muscle cells and intramuscular septa in the taenia coli.

Bands of electron-dense material beneath the cell membrane of smooth muscle cells of the guinea-pig taenia coli provide attachment to thin myofilaments and to intermediate (10nm) filaments; about 50% of the cell membrane is occupied by dense bands in muscle cells transversely sectioned at the level of their nucleus, and between 50 and 100% in small cell profiles nearer the cell's ends. In addition to the known cell-to-cell junctions (intermediate contacts), more complex apparatuses anchor muscle cells together, either end-to-end or end-to-side of side-to-side. They consist of elaborate folds, invaginations and protrusions accompanied by large amounts of basal lamina material. In the end-to-end anchoring apparatuses numerous finger-like and laminar processes from the two cells interdigitate. Other muscle cells have a star-shaped profile in the last few microns of their length, or show longitudinal invaginations occupied by a thickened basal lamina and occasionally by collagen fibrils. The septa of connective tissue extend only for a few hundred microns along the length of the taenia. In taeniae fixed in condition of mild stretch the muscle cells form an angle of about 5 degrees with the septa. In muscles fixed during isotonic contraction the angle increases to about 29--22 degrees, and in longitudinal sections the muscle cells appear arranged in a herring-bone pattern. The collagen concentration in the taenia coli is 4--6 times greater than in skeletal and cardiac muscles. These various structures are discussed in terms of their possible role in the mechanism of force transmission.


Effects of isolation and transplantation of the corpus cardiacum on hormone release from its glandular cells after flight in Locusta migratoria. A quantitative electron microscopical study.

The glandular lobe of the corpus cardiacum (CC) of Locusta migratoria contains secretory cells and axon terminals. It is generally accepted that the glandular cells produce an adipokinetic hormone which stimulates the release of diglycerides from the fat body. The axon terminals are supposed to be involved in the regulation of the secretory activity of these cells. CC were transplanted into locust hosts. The secretory activity of the glandular cells and axons was studied in the transplants as well as the intact host CC. Quantitative electron microscopical examination of the glandular cells of the CC in animals both at rest and after flight shows that only in the host CC the secretory activity of the glandular cells is stimulated by flight, as indicated by an increase in the activity of the Golgi zones and in the number of exocytotic pits. In the axon terminals release of secretory products, indicated by synaptic vesicles and membrane indentations, is reduced as a result of the transplantation. It is concluded that the glandular cells need excitatory input from outside the CC for stimulation of their secretory activity. Furthermore, it is proposed that the transplanted glandular cells decrease the level of activity of the intact host cells by way of a negative feedback mechanism.


Electron microscopic studies of the innervation of the human spleen.

The innervation of four normal human spleens was investigated by electron microscopy. Unmyelinated nerve fibers accompanied the arterial vascular system up to the arterioles of the red pulp. Neither myelinated nerve fibers nor ganglion cells were seen in the splenic hilum or in the splenic tissue itself. The nerve fibers terminated against the smooth muscle cells of the blood vessels in a manner that is typical of the autonomic nervous system. The terminal axons contained small and large granular vesicles and thus were adrenergic nerve fibers. In contrast to the results of previous studies using silver impregnation methods innervation of the red or white pulp could not be demonstrated. The findings on human spleens agree with those on mammalian spleens obtained by other authors using ultrastructural and fluorescence histochemical methods.


Functional mediation of compensatory enlargement of the parotid gland.

The role of functional activity in mediating compensatory enlargement of the parotid gland after removal of the other major salivary glands was investigated. Increased levels of activity were achieved by feeding rats a bulk diet. Conversely, a liquid diet was used to reduce the functional demands on the parotid. It was found that the liquid diet completely prevented the compensatory response from occurring. Bulk diet, on the other hand, caused an even greater compensatory response than did the standard chow diet. Compensatory enlargement of the parotid, therefore, depends on its functional activity and not on other, e.g., humoral factors dissociated from function. The character of the cellular response in compensatory enlargement was also examined. The chow diet caused compensatory enlargement by an increase in cell size with little, if any, increase in cell number.


Ultrastructure of the different fibre types in axial muscles of the sharks Etmopterus spinax and Galeus melastomus.

Red, intermediate and white axial muscle fibres of the sharks Etmopterus spinax and Galeus melastomus were studied by electron microscopy and morphometry. The mitochondrial content is more than thirty percent in red, less than one percent in white, and up to fifteen percent in intermediate fibres. About one third of the mitochondria in red fibres are accumulated close to the sarcolemma. Red fibres contain much glycogen, present as rosettes (alpha particles). Intermediate fibres contain less glycogen (as beta particles). White fibres have scarcely any visible energy reserves. Red fibres contain slightly less (4-5%) of the sarcotubular system than the other fibre types (6-8%). In all fibre types, the terminal cisternae of the SR are regularly divided by clefts. Triads or dyads are generally positioned at the Z discs, but in Galeus white fibres two dyads may be present, one on each side of the Z disc. The morphology is discussed in relation to current views on the functions of different muscle fibre types.


Cytochemical localization of acid phosphatase in regenerated and dark-adapted eyes of a snail, Helix aspersa.

The role fo the Golgi apparatus and the Golgi-endoplasmic reticulum-lysosomal complex (GERL) in the formation of lysosomes in the photosensory cells of regenerating and dark-adapted eyes of the garden snail Helix aspersa was examined with use of acid phosphatase as a marker enzyme. In newly regenerated eyes, lead reaction deposit was restricted to the cisternae of GERL, a few small vesicles and some large secondary lysosomes. Dark-adapted sensory cells, on the other hand, were characterized by a heavy reaction product in the hypertrophied Golgi cisternae and GERL. Primary lysosomes were packaged by GERL cisternae in both the regenerating and the degenerating dark-adapted eyes. In the latter, these lysosomes may have been produced also by the Golgi apparatus. No reaction product was found in the rough endoplasmic reticulum, microvilli, or large aggregations of 800 A photic vesicles in either kind of eye. In this study the lytic activity in differentiating sensory cells was significantly lower than that in degenerating cells suggesting that the increase in lysosomal activity in the latter was due to the absence of light. The effects of long dark-adaption appear to be: 1. decrease in the production of photic vesicles; 2. increase in the formation of lysosomes; and 3. breakdown of photic vesicles by lysosomal activity.


On the ultrastructure of the abdominal sense organ of the giant scallop, Placopecten magellanicus (gmelin).

The abdominal sense organ of the giant scallop, Placopecten magellanicus, is composed of two cell types. The presumed receptor cells bear a single cilium 60 to 70 micrometer in length. The microvilli at the apices of these cells may also be modified into microvillous whorls. From eight to twelve ciliated cells are associated with a single mucous cell. The mucous cells have a much greater diameter than the ciliated cells and contain many electron-dense mucous granules. No function has yet been determined for the ciliated cells, although a number of theories are presented.


Ultrastructural studies on the ciliated receptors of the long tentacles of the giant scallop, Placopecten magellanicus (gmelin).

The long tentacles of the Giant scallop Placopecten magellanicus (Gmelin) have been examined with light, scanning, and transmission electron microscopy. Three types of ciliated cells have been observed, one of which is located in specialised papillae born on the distal third of the tentacle. There are two separate cell types within the papillae. Type I cells are non-ciliated supporting cells, which form a capsule within which are found the Type II cells. These cells bear up to five cilia at their apices, and it is suggested that these are the receptor cells of the organ. No function has yet been determined for the receptors, but is suggested that they might be mechanoreceptors. A third cell type, Type III cells, occur at the base of the papillae. These cells bear many cilia and also macrocilia. Another ciliated cell type occurs on the proximal two thirds of the tentacle. These cells bear many cilia that are thought to be motile and not sensory.


Identification of a secretomotor centre in the brain of Locusta migratoria, controlling the secretory activity of the adipokinetic hormone producing cells of the corpus cardiacum.

After retrograde filling of axons terminating in the glandular lobe of the corpus cardiacum (CC) of Locusta migratoria with cobalt chloride, a paired group of about 15 cobalt containing cells was demonstrated in the lateral area of the protocerebrum. The axons of these cells run via the NCC II into the glandular lobe of the CC. These small neurons have the characteristics of secretory cells; they contain secretory granules of about 1000 A in diameter. The axon terminals in the glandular lobe, making synaptic contacts with the glandular cells, contain secretory granules of the same size. It is therefore concluded that the cell groups in the protocerebrum control the activity of the glandular cells which produce an adipokinetic hormone. Arborizations of fibers of the lateral secretomotor cells are present in the dorsal neuropile of the protocerebrum, ventral of the mushroom bodies and along the tracts of the NCC I within the brain. It is proposed that these arborizations are sites of synaptic input. It is discussed that the axons of these cells might receive additional synaptic input in the storage lobe of the CC. The localization of cell bodies, the axons of which enter the storage part of the CC is described. The course of the axon tracts of the various cell groups in the protocerebrum and their connections with the NCC I and NCC II are demonstrated.


The ultrastructure of an olfactory sensillum on the maxillary palps of locusta migratoria (L.).

The olfactory sensilla on the maxillary palp tip of Locusta migratoria (L.) resemble the surrounding contact chemoreceptors in general morphology. The perforated peg has a thicker wall than is commonly found in olfactory sensilla. The form and position of the sensilla are considered in relation of the olfactory function. The fine structure of the dendrites is discussed in relation to that described in other olfactory sensilla.


Effect of actinomycin D on the structure of the chromatoid body in the rat spermatids.

The effect of actinomycin D on the chromadoid body of rat spermatids has been studied by light and electron microscopy, high resolution autoradiography and biochemical methods. Actinomycin D caused structural changes in the chromatoid body of young round nucleated spermatids. The normal irregularily lobulated chromatoid body acquired a ring-like configuration 12 h after an intratesticular injection of 2 microgram of the drug. The labelling of the chromatoid body with 3H-uridine which can normally be seen after 12 h was also abolished by actinomycin D. These observations lead to the suggestion that the chromatoid body contains a store of long-lived mRNA molecules that are activated later during spermiogenesis when transcription in the spermatid nucleus has ceased but a high level of protein synthesis still persists.


Septate junctions in the cephalic epidermis of Turbellarians (bipalium).

In the epidermis of turbellarians septate junctions of the pleated sheet type have been demonstrated in conventional thin sections and freeze fractured preparations. The structure of these junctions entirely agrees with that found in molluscs and arthropods.


Hemoglobin synthesis in cell hybrids formed between teratocarcinoma and Friend erythroleukemia cells.

Viable hybrid cells have been isolated following fusion of Friend erythroleukemia cells and undifferentiated teratocarcinoma cells. The hybrids formed between near-diploid parental cells resembled Friend cells in the ability to grow in suspension and to synthesize hemoglobin in the presence of the chemical inducers dimethyl sulfoxide (DMSO) and ouabain. Erythropoietin (EPO) was effective in inducing hemoglobin synthesis in some of the hybrid cell lines. The hemoglobins synthesized by the hybrids were of the adult forms, but were quantitatively different from those hemoglobins synthesized by the parental Friend cells, suggesting that the fusion event modulated the expression of the hemoglobin chain genes.


Germ line integration of moloney leukemia virus: effect of homozygosity at the m-mulV locus.

Mice genetically transmitting the exogenous Moloney leukemia virus (M-MuLV) have been previously derived. These animals carried one copy of M-MuLV DNA in their germ line and were heterozygous for the M-MuLV locus (Jaenisch, 1976). Experiments were performed to investigate whether homozygosity at the M-MuLV locus would be compatible with normal development. Animals heterozygous for the M-MuLV locus were mated [female (+/-) X male(+/-)] and the genotype of the offspring was analyzed. Molecular hybridization experiments revealed three classes of offspring carrying two copies (++), one copy (+/-) and no (--) M-MuLV-specific DNA sequences, respectively, in their liver DNA. Genetic experiments indicated that males of the first class transmitted the virus to 100% of their offspring, males of the second class to 50% and males of the third class not at all when mated with normal females. These results demonstrated that homozygosity at the M-MuLV locus has no detectable effect on normal development of the animals and that the M-MuLV gene is transmitted from one generation to the next strictly according to Mendelian expectations. Development of M-MuLV-induced leukemia is not influenced by the genotype of these animals--that is, animals carrying two or one copies of M-MuLV in their germ line or animals congenitally infected from the mother developed disease at similar rates.


The initiation sites for RNA transcription in Ad2 DNA.

Six restriction fragments of Ad2 DNA which contain sites for RNA initiation have been identified by their ability to hybridize nascent labeled RNA less than 1 kb in length. Four RNA initiation sites early in infection are identified in regions where previous work (Flint, 1977) had mapped mRNAs. The major late RNA initiation site is the origin of a giant nuclear transcript extending from approximately 16.3 map units to (or close to) 100 units at the end of the genome. This transcription unit encompasses at least four or five mRNA sites; processing of this long transcript appears necessary to generate the mRNA.


The gene and messenger RNA for adenovirus polypeptide IX.

A small RNA species, distinct from the VA RNAs, has been identified in HeLa cells infected with adenovirus type 2. The RNA, which has been purified using a novel screening procedure, is polyadenylated, sediments at 9S and has an estimated length of 550 nucleotides. In a cell-free translation system, the 9S RNA directs the synthesis of virion polypeptide IX, molecular weight 12,000 daltons. The location of its gene has been established by hybridization of the RNA to fragments of viral DNA produced by cleavage with restriction endonucleases: it spans position 10.0 on the r strand of the viral genome. These results unexpectedly place the gene for a "late" protein within a region of the genome which is transcribed early during infection


Inhibition of colchicine binding to rat liver tubulin by aldehydes and by linoleic acid hydroperoxide.

The onset of fat accumulation within CCl4 poisoned hepatocytes, occurring as early as 1 h after treatment, is known to be provoked by a block in lipoprotein secretion. Lipoprotein secretion involves the function of the microtubular system. Several data indicate that this early block in lipoprotein secretion is not primarily the consequence of impaired protein synthesis. Therefore effects of some derivatives of lipid peroxidation, i.e. aldehydes and linoleic acid hydroperoxide were investigated. The results described in this paper shown that the above mentioned lipid peroxidation derivatives inhibit, with different activities, [3H] colchicine binding to liver high-speed supernates. Percentage binding inhibition is directly related to concentrations of aldehydes of LAHPO. LAHPO is more effective than aldehydes. Among the aldehydes tested, 4-hydroxypentenal, produced during lipid peroxidation of biological materials, was the most active. The presence of thiols, added to the incubation medium, partially protects against the inhibition of [3H] colchicine binding by aldehydes. This suggests that aldehydes act by reacting with -SH groups of tubulin. The possibility that interaction between lipoperoxidation derivatives and tubulin in vivo may contribute to the onset of fat infiltration in CCl4 poisoning is discussed.


Copper thionein in the kidneys of copper-poisoned sheep.

A study has been made of the distribution of copper in the kidneys of  copper-poisoned sheep, containing up to 240 microgram copper/g fresh cortex. About 64% of the copper in the cortex was present in the cytosol and 75% of this occurred in a form with molecular weight of approx. 12 000. This was partially purified by gel filtration on Sephadex G-75 and Bio-Gel P.10 and ion exchange chromatography on DEAE Sephadex A-25 to give three sub-fractions, which also contained zinc. The amino acid composition, copper content and chromatographic behaviour of these proteins indicated that they were copper-thioneins. No significant amounts of the proteins were detected in the plasma or erythrocytes of the copper-poisoned sheep when they were undergoing the haemolytic crisis typical of this syndrome. It is concluded that metallothionein constitutes the major copper-binding protein in the kidneys of copper-poisoned sheep. However the rapid accumulation of the protein in the kidney, and the development of kidney damage, are unlikely to have arisen from the release of the intact copper-protein from the liver and its transport via the blood to the kidneys.


In vivo alkylation studies with dichlorvos at practical use concentrations.

Twenty male CFE rats were exposed to atmospheres containing 0.064 microgram/l of [Me-14C] dichlorvos (113 Ci/mol) for 12 h. Analysis of the DNA and RNA from the total soft tissues of these rats revealed no methylation of the N7 atom of guanine moieties. The limits of detection of methylation were one methyl group per 6.0 X 10(11) and per 2 X 10(9) nucleotide units for DNA and RNA, respectively. Only 0.000001% of the administered dose would have needed to react with DNA in order to produce detectable methylation of this macromolecule. The exposure period employed in this study (12 h) constituted a significant fraction of the half-life of 7-methylguanine moieties in DNA (3 days). On the basis of this information and the extremely rapid metabolism of dichlorvos in a wide range of mammalian tissues and species it was concluded that dichlorvos does not methylate the nucleic acids of mammalian tissues when it is inhaled continuously at practical use concentrations.


Cytopathogenic effects of atoxyl, an ototoxic compound, on human diploid fibroblasts in vitro.

Atoxyl, an arsenic compound, may cause degeneration in vivo of the inner ear including cells of the stria vascularis and hair cells. The mechanism behind the cytotoxic effect is not known. The effects of atoxyl at the subcellular level were investigated in this study using human diploid embryonic lung fibroblasts in monolayer cultures as an in vitro model system. Atoxyl caused a subtle but significant increase in the permeability of the fibroblast plasma membrane, as measured by release of a low molecular weight cytoplasmic marker (alpha-amino isobutyric acid). At higher concentrations or after longer incubation times, protein synthesis was impaired. This effect occurred in parallel with alterations in the cellular morphology as viewed by light microscopy. In the final stages of atoxyl intoxication the cells released also a higher molecular weight marker (nucleotide), indicating a further increased membrane permeability following the primary damage. It is concluded that atoxyl exerts a dual effect on the human fibroblasts, namely on membrane permeability and protein synthesis. Although the concentrations used were higher than those exerting the ototoxic effects in vivo, the prolonged exposure times to low concentrations obtained in whole animals may very well compensate for this fact. The effects observed in the in vitro fibroblast model system may thus be relevant to the mechanism of action of atoxyl during induction of ototoxic effects in vivo.


[Surgical treatment of gastric carcinoma in the elderly. Clinical considerations on a group of patients undergoing major surgical destruction].

A group of 24 patients in senile age was subjected to major demolition operations, for purposes of radical removal of gastric carcinoma (total gastrectomy, subtotal resection, oesophago-gastric resection). In six patients the major operation was widened by partial demolition of neighbouring organs (liver, colon, pancreas). The flattering results (both immediate and long-term) obtained from this operation and the progress reached in the knowledge and correction of the senile physiopathological alterations allow encouraging developments to be forecast for this surgery, the success of which is subject to careful tactical selections and to close multidisciplinary cooperation directed to strengthening vital reserves, assistance of main functions and prompt recognitions and treatment of any complications.


[Role of the vasa vasorum in the process of remote vascularization of the Wesolowski Weavenit arterial prosthesis (experimental research)].

Experimental research was carried out for the purpose of studying the behaviour of the vasa-vasorum in a group of animals in which, by means of a Weavenit prosthesis, the section of aorta lying between the branches of the renal arteries and the trifurcation of the terminal oartic section had been substituted. From the results of the research the Authors conclude by asserting that above all the technique they used allowed excellent visualisation of the vasa-vasorum, as shown both by the histological preparation coloured with haematoxylin-eosin and by the preparations carried out under the stereomicroscope. Furthermore, in the microscopic observations there is the indisputable presence of vessels of varying calibre which, from the neo-adventitia through the meshes of the prosthesis, are carried to the level of the neointima, confirming that the vasa-vasorum constitute the most important reactive phenomenon for purposes of vascularisation of the prosthesis.


[Use of mannitol and propranolol in the treatment of experimental acute renal failure (histomorphological study)].

Experimental research was carried out in order to ascertain whether administration of drugs capable of acting on the renal circulation, such as mannitol and propanol, in addition to improving the renal function, also have a protective effect on the histomorphological alterations induced by the acute renal ischemia. On the basis of the results of the research the Authors conclude by asserting that the combined use of mannitol and propanol has a real protective effect in preventing or attenuating lesions of the kidney caused by serious acute renal failure.


[Leiomyosarcoma of the esophagus].

The authors describe the anatomo-clinical characteristics of a case of leiomyosarcoma of the oesophagus which came under their observation, emphasizing its rarity: 39 cases in the literature examined. They then discuss the numerous problems that this neoplasia involves, especially diagnostic differentiation from other sarcomas and the pseudo-sarcomatous reaction of the stroma during the course of carcinomas. Lastly they divide leiomyosarcoma of the oesophagus into polypoid forms and infiltrating forms, owing to the different therapeutic and prognostic implications that such distinction implies.


[Value of transduodenoscopic wirsungography in the diagnosis of pancreatic pseudocysts].

The radiographic pictures obtained by endoscopic wirsungraphy in a group of 24 patients suffering from pancreatic pseudocysts and subsequently examined intraoperatively by wirsungraphy and cystography are analysed and commented. Pre-operative endoscopic visualisation of the lesion was obtained in 70% of the cases. In 55% of the cases there were co-existing alterations of calibre and trend of the main pancreatic duct, chiefly attributable to chronic basic pancreatitis and to a very small extent to the pseudocystic lesion. The following are discussed: a) the diagnostic value of the endoscopic procedure, which reaches absolute values in the direct visualisation of the sac, with a power of resolution that is difficult to reach with other methods; b) the probable prognostic significance with reference to the not absolutely precluded possibilities of spontaneous regression; c) the notable usefulness of the procedure, combined with intra-operative wirsungraphy and cystography, for anatomo-topographical definition of the lesion and its relations with the ductal system, indispensable for a correct formulation of the surgical tactic.


[The post-cholecystectomy cystic-stump syndrome].

A study was made of five patients, all of female sex, suffering from cystic stump syndrome, occurring among a total of 726 operations on the biliary ducts performed from January 1959 to June 1975, and hence with the incidence of 0.7%. The diseases which brought the patients to the operating table consisted of two cases of long cystic stump, two cases of neuroma of the cystic stump, and one case of asymptomatic long cystic stump with the presence of a serous cyst of the head of the pancreas. The surgical operation always consisted in the removal of the long cystic stump or the neuroma and led to the patient's cure in each case. It is asserted that the cystic stump syndrome must be considered as a nosological entity in itself, affecting patients operated on the bile ducts with a by no means negligible frequency. After considering the various pathogenetic hypotheses covering this syndrome, the Authors finally conclude by reiterating the necessity of careful isolation of the cystic duct during a cholecystectomy operation and of its resection very close to the hepatocholedochus, and then to carry out reliable and effective prophylaxis of the often considerable disturbances which may threaten the results of the operation. Once the syndrome has established itself, however, removal of the cystic stump becomes essential to cure of these patients.


[Pathology of Meckel's diverticulum. Apropos of a case. Notes on surgical anatomy and surgical technic].

Remembering an observed case of intestinal invagination from Meckel's diverticle the A. describe the most important anatomical and anatomo-surgical characteristics of the diverticle of Meckel, laying particular stress on the variation in form; position and size with reference to the part they have in surgical operations. The operation tecnique of transportation of the diverticle in its various pathologic cases is also a point treated in this work; the principle methods of ablation are brought up to date with synthetic iconography.


Ultrastructural changes in the gastric mucosa following hemorrhagic shock in pigs.

Ultrastructural changes in the gastric mucosa of 14 piglets subjected to transient hemorrhagic shock (3 hr duration; mean arterial pressure 40 mmHg) are described. After 30 min there was mucosal edema and extravasation of red blood cells. Microthrombi with degranulating thrombocytes and fibrin strands were seen in the capillaries. These changes were also seen in the antral mucosa where no subsequent ulceration usually occurs. At this stage the cells of the neck region of the gastric glands showed mitochondrial dilatation and their apical parts were seen to bulge into the lumen of the gastric glands. Other cell types were affected later and necrosis progressed from the surface into deeper parts of the mucosa. Mast cells and mucosal endocrine cells were relatively resistant, being mostly undamaged at the end of the shock period and later. The findings suggest that, during the shock, local formation of thrombi contributes to mucosal ischemia and ulcer formation, and that the cells at the neck region of the gastric glands form the locus of limited resistance to ulcerogenic effects.


Intestinal lysosomal enzyme activity in regional simulated shock: influence of methylprednisolone and albumin.

A 2 hr-period of regional intestinal simulated shock in cats results in small intestinal mucosal lesions and a general cardiovascular derangement, probably secondary to the release of cardiotoxic material into the intestinal venous blood. These phenomenona are accompanied by release of lysosomal and cytoplasmatic enzymes from the intestinal tissue. The effects of methylprednisolone treatment and deposition of albumin in the intestinal lumen during the regional shock period were studied. Administration of methylprednisolone early and late in the regional shock period prevented mucosal lesions and cardiovascular deterioration as well as lysosomal and cytoplasmatic enzyme release. Albumin deposition in the intestinal lumen during the regional shock period prevented lysosomal enzyme release and cardiovascular derangement and to a minor extent mucosal lesions. It is suggested that release of intestinal lysosomal enzymes is of importance for development of mucosal lesions and for production of cardiotoxic material.


Cerebral hemodynamics, vascular reactivity, and metabolism during canine endotoxin shock.

Cerebral hemodynamics, vascular reactivity, and metabolic alterations were studied in anesthetized, spontaneously respiring dogs for 4-6 hr of gram-negative endotoxin shock. Cerebral venous outflow (cerebral blood flow) was measured directly from the cannulated confluence of the sagittal, straight, and lateral sinuses, with the lateral sinuses occluded. Cerebral blood flow and cerebral perfusion pressure decreased immediately upon administration of 1,2, or 5 mg/kg endotoxin and consistently remained below control values. By the fourth hour of shock, cerebral blood flow was decreased 37, 48, and 45% respectively. Cerebral vascular resistance initially decreased, then progressively increased to levels significantly above control, and it was primarily responsible for the reduced cerebral blood flow in the later stages of shock. Cerebral autoregulatory and "venous-arteriolar" responses were well maintained, although cerebral vascular reactivity to arterial hypercapnia was depressed. Cerebral venous blood pH and pO2 decreased, and arterial-venous differences of percentage oxygen saturation, total CO2, and HCO3 increased. These alterations in cerebral vascular hemodynamics and tissue acid-base balance indicate that cerebral ischemia and resulting acidosis occur during canine endotoxin shock.


Comparative splanchnic blood flow effects of various vasodilator compounds.

We examined the visceral blood flow distribution during infusion of three vasodilators at doses that produced similar depression of systemic arterial pressure. The studies were performed in pentobarbital-anesthetized dogs using the radioactive microspheres technique. Minoxidil did not alter renal, total visceral, or visceral organ flow distribution with the exception of a modest increase in relative stomach blood flow. Nitroprusside increased the percentage of total visceral flow to the spleen and the hepatic artery. Dopamine increased blood flow to the stomach, intestine, and kidney. After phenoxybenzamine, the augmentation of stomach blood flow by dopamine was greatly increased, while blood flow to the splenic, pancreatic, and hepatic arteriolar vascular beds decreased. The decreases in blood flows may be due to decreased perfusion pressure in the absence of active vasodilation or to myogenic or metabolic autoregulation. Thus, at equivalent hypotensive responses, the vasodilator compounds that we studied produced markedly different patterns of visceral blood flow.


Blood flow in rats during hemorrhagic shock: differences between surviving and dying animals.

Cardiac output distribution was measured during hemorrhage and hemorrhagic shock in unanaesthetized rats. In comparison to control animals, a varying degree of decreased blood flow was found in the skin, kidneys, splanchnic bed, and carcass. Bronchial and hepatic arterial blood flows were within normal limits for the entire experiment. Whereas the coronary blood flow fluctuated between values higher and lower than normal, the cerebral blood flow values were normal or decreased. When survivors were compared to dying rats, differences were foun in the early and late stages of shock. Initially, the carcass flow in survivors was higher, while the splanchnic flow was lower, than in dying rats. This redistribution of cardiac output may be responsible for an increased venous return and improved chances for survival. At the late stages of shock, survivors had significantly higher bronchial and hepatic arterial blood flow.


The chemical nature of a pancreatic cardiodepressant factor.

The presence of a cardiodepressant factor of pancreatic origin has been reported in the plasma of experimental animals and man in a variety of shock states. It has been suggested that the depression of developed tension of the isolated cat papillary muscle may be caused by excess NaCl in the bathing medium rather than a specific cardiodepressant peptide. Incubated pancreatic homogenate was used as a source of this factor, and after protein precipitation, ultrafiltration (10,00 and 1,000 MW), dialysis and lyophilization, the residue was applied to a Sephadex G-10 column in order to ensure the removal of all salts. The protein effluent of the Sephadex column contained all the cardiodepressant activity of the filtered, dialyzed pancreatic homogenate and none of the salt content. To further isolate this cardiodepressant factor, the active residue was applied to a cellulose column and eluted with butanol: glacial acetic acid: water (25:26 v/v/v). This elution gave 8 distinct peptide peaks, one of which, peak 4, contained significant depressant activity. Thus, a cardiodepressant peptide of approximately 250-1,000 MW exists in pancreatic homogenates and this compound is not excess NaCl in the assay system.


Effects of ganglionic blockade upon the renal and cardiovascular dysfunction induced by thermal injury.

Studies to test the effects of partial ganglionic blockade on renal and cardiovascular function were carried out in 16 mongrel dogs that under chloralose anesthesia had been subjected to full thickness flame burns to approximately 25% of their body surface. All animals received intravenous fluid replacement according to the same resuscitation formula we use in burned children. Half of the animals received 0.3 mg/kg of chlorisondamine hydrochloride 40 minutes after the burn; the remaining 8 dogs received only the vehicle. Among the variables monitored before burning and before and after blockade were glomerular filtration rate, renal plasma flow, water and osmolar clearance, sodium and potassium excretion, cardiac output, mean arterial, right atrial, and left ventricular end diastolic pressure, peripheral resistance, peak dP/dt/P, blood pH, and blood gases. Analysis of the data has revealed that pharmacologic blockade of the sympathetic system during the immediate postburn period results in a marked improvement in cardiac output and moderate improvement in kidney function.


Skeletal muscle pH, CO2, and electrolyte balance during hemorrhagic shock.

Previous reports have indicated a significant degree of hindlimb skeletal muscle vasodilation coincident with the decompensatory phase of shock induced by prolonged hemorrhagic hypotension. The first objective of the present investigation was to examine the relationship between this apparent vascular decompensation and the arterial and venous skeletal muscle PO2, PCO2, VO2, VCO2, pH, Na+ and K+. The second objective was to examine the possibility that a stable blood-borne, remotely or locally released, vasodilator substance caused the vascular decompensation. Anesthetized dogs were bled in 5 ml/kg steps into a suspended reservoir until mean arterial pressure (MAP) was 35-40 mm Hg; this pressure was maintained until signs of decompensation were apparent. The blood remaining in the reservoir was returned and the animals were followed until MAP fell below 50 mm Hg. MAP, central venous pressure (CVP), lead II of ECG, heart rate (HR), and skeletal muscle venous flow were monitored and correlated with arterial and venous CO2, O2, and electrolytes. The results suggest that the skeletal muscle vascular decompensation was not caused by a stable blood-borne substance but may at least in part be due to the increased H+ and K+ in skeletal muscle blood and to mild skeletal muscle hypoxia.


Histamine biosynthesis in shock.

The histidine decarboxylase activity of the lung and spleen was determined in rats made resistant to trauma either by prior sublethal exposure or by injection of extracts prepared from the spleens and plasma of trauma-resistant rats. The data describe the posttraumatic period in the normal animal as being associated with an increased histidine decarboxylase activity. In trauma-resistant animals, changes in the enzyme activity were prevented in the lung and were less pronounced in the spleen. The administration of extracts from trauma-resistant rats was similarly effective in impeding the changes in enzyme induction following trauma. It is suggested that an active humoral factor previously shown to be elaborated during conditioning and associated with the RES may act by inhibiting the activation of histidine decarboxylase.


The effects of reserpine on myocardial lesions in dogs subjected to hemorrhagic shock.

Anesthetized dogs were subjected to severe hemorrhagic hypotension, with blood pressure maintained at 35 mm Hg for 30 or 90 minutes. In these dogs myocardial zonal lesions were present and subendocardial hemorrhage and necrosis resulted. In two other groups of dogs, similarly subjected to hemorrhage but previously depleted of catecholamines by a 3-day regime of reserpine treatment, there was a markedly lower or no incidence of myocardia lesions.


Effects of dopamine on endotoxin and hemorrhagic shock in the canine stomach.

Studies were conducted to evaluate the effects of dopamine on gastric electrophysiopathology in endotoxin and hemorrhagic shock. Intraarterial infusion of dopamine (15.5 or 31 microgram/kg/min) in the in vivo stomach preparation produced an immediate decrease in electrical potential difference (PD), which then returned and exceeded control values. No changes in resistance (R) and blood pressure were observed. These electrophysiological responses of the gastric mucosa to dopamine are very similar to the actions of epinephrine. The in vitro studies demonstrated that active transport of Na+ was stimulated with an addition of dopamine or epinephrine (2 X 10(-4) M) to the serosal solutions of the isolated gastric mucosa. In addition, the in vivo studies demonstrated that both 40% hemorrhage and 1 mg/kg of endotoxin given as an intravenous bolus decreased PD and blood pressure and increased R although dopamine was continuously infused intraarterially for 60 minutes prior to and following hemorrhage or endotoxin. Administration of endotoxin at the onset of dopamine infusion decreased both blood pressure and PD initially. While PD showed a complete recovery at a later stage, blood pressure never returned to control levels. These results, combined with previous observations, suggest that: 1) dopamine has no beneficial action on the gastric mucosa during hemorrhagic or endotoxin shock; 2) dopamine acts on the electrophysiology in vivo and Na+ fluxes in vitro in the gastric mucosa in a manner similar to epinephrine; and 3) decrease in blood flow may be responsible for the observed decrease in transmural PD after dopamine and epinephrine in vivo.


Platelets, fibrinogen, and pulmonary haemodynamics in early experimental septic shock.

The relationship between platelet trapping, fibrinogen, and pulmonary haemodynamics after iv injection of disintegrated Pseudomonas bacteria into dogs were studied. Platelets were labeled with 51Cr and fibrinogen with 125I. The number of circulating platelets and white cells decreased abruptly within 2 minutes after injection, remained low at 5 minutes, and thereafter slowly increased. At the same time there was a transient increase of 51Cr activity in the lung occurring simultaneously with a decrease in cardiac output and an increase in pulmonary vascular resistance. Pulmonary artery pressure remained constant during the first phase of the experiment and thereafter decreased. There were no signs of 125I-fibrinogen accumulation in the lungs during the 2 hours of the experiment. The results indicate that trapping of platelets and eventually leucocytes in the lungs are closely related to the initial pulmonary haemodynamic changes after injection of disintegrated bacteria, possibly both by release of vasoactive substances and mechanical blocking. This microembolism in the pulmonary microcirculation might be of importance for the development of the shock lung syndrome.


Favorable influence of dopamine on left ventricular performance in patients refractory to discontinuation of cardiopulmonary bypass.

Of 410 consecutive patients undergoing cardiopulmonary bypass, 13 (3.2%) required pressor and inotropic support beyond volume replacement with whole blood and administration of CaCl2 to discontinue bypass. In 4 patients, isoproterenol was ineffective in maintaining cardiac output and systemic arterial pressure. In 12 patients addition and/or substitution of dopamine permitted discontinuation of cardiopulmonary bypass. In 7 patients who had serial hemodynamic measurements, mean systemic arterial pressure increased by 26%; cardiac index increased by 36%; stroke volume increased by 31%; and stroke work index increased by 83% (all p less than 0.005). There were no significant changes in central venous and mean pulmonary arterial wedge pressures, heart rate, or pulmonary and peripheral vascular resistances. Eleven of the 13 patients survived. We conclude that dopamine is an effective pressor and inotropic agent in the management of left ventricular dysfunction immediately after cardiopulmonary bypass.


The role of the canine spleen in cardiovascular homeostasis during halothane anesthesia.

Barbiturate anesthesia is known to increase canine splenic sequestration of red blood cells. In our laboratory, high halothane concentrations have produced a decreased arterial hematocrit in the dog. In order to assess the role of the spleen in this phenomenon, central hematocrit, plasma volume, and ventricular hemodynamics were studied at low and high halothane concentrations before and after splenectomy in the same group of dogs. Although the hematocrit difference was less after splenectomy, it was not abolished. In addition, there was more cardiovascular depression by equivalent or lower halothane doses after splenectomy. It appears that the dog has other areas of red cell sequestration than the spleen accounting for the persistently lower hematocrit with high halothane concentrations after splenectomy. The modifying effect of the canine spleen on the circulatory depression produced by halothane should be taken into account when the drug is used in the dog.


Pulmonary insufficiency produced by norepinephrine: a comparison with epinephrine.

An intravenous infusion of norepinephrine, 2 microgram/kg/min, for 5 hr in anesthetized, mechanically ventilated dogs produced a statistically significant increase in the pulmonary shunt, the cardiac output, and the mean pulmonary artery pressure, but no significant change in the pulmonary wedge pressure and the pulmonary vascular resistance except at 5 min. These hemodynamic changes are qualitatively similar to those produced by the same dose of epinephrine infused for the same time period. However, there were differences in the magnitude of the hemodynamic changes between norepinephrine and epinephrine, as might on the basis of their different pulmonary pharmacologic effects, but the changes were not statistically significant at all times, and more studies are necessary to determine if the differences are real. These studies add support to the thesis that adrenergic stimulation plays an important role in the pathogenesis of the pulmonary insufficiency associated with shock.


Role of colonic bacteria in the pathophysiology of fecal peritonitis.

This study was designed to clarify the role of colonic bacteria in the reactions accompanying fecal peritonitis. Rats were subjected to septic or nonseptic peritonitis induced by fresh fecal suspensions or suspensions pretreated with heat or antibiotic. Measurements during 8 hr in rats with septic peritonitis recorded bacteremia, hypoglycemia dn progressive hemoconcentration, lactacidemia, and hypocapnea. Mortality was 100% by 24 hr. Nonseptic peritonitis produced significantly lesser degrees of hemoconcentration and hypocapnea. Plasma lactate remained in control ranges while plasma glucose concentrations increased slightly. Mortality was 5% in 24 hr. Parameters in control rats were stable over 8 hr. Hepatic oxygen supply was estimated in each group by multiple platinum wire electrodes. Severe hepatic hypoxia was recorded by 6 hr in rats with septic peritonitis. By contrast, nonseptic peritonitis caused a comparatively mild degree of hypoxia. The pathophysiologic developments in septic rats appear to be largely the result of hypovolemia induced by colonic bacteria. Administration of a colloid solution was effective in preventing its development.


Intravascular platelet aggregation and acute respiratory insufficiency.

Respiratory effects of long-lasting episodes of intravascular platelet aggregation have been studied in cats. Animals in 1 group had the chest opened and were given mechanical ventilation with a constant tidal volume. Animals of another group were breathing spontaneously. Platelet aggregation was induced by intravenous infusion (for 1 hr) of a suspension of collagen fibrils. Such infusions caused acute respiratory distress in both groups. Severe arterial hypoxemia and rapid breathing as well as constriction of airways and lung vessels occurred. Most of these changes were reversed within 2 hr after collagen infusion had ended. Deep lung inflations markedly improved lung function. It is concluded that an acute, but reversible pulmonary insufficiency might be caused by pulmonary microembolization due to intravascular platelet aggregation. The arterial hypoxemia is suggested to be caused by disturbances in the ventilation-perfusion ratio secondary to airway constriction and closure. The present findings also imply that besides platelet aggregation, some additional factors are necessary for irreversible or progressive respiratory insufficiency to develop.


Multiple pathways of capillary permeability.

Morphological and physiological studies indicate multiple routes for transport across capillary endothelium. However, the identification of the morphological counterparts of specific transport processes (or the assignment of specific transport roles to morphologically identifiable pathways) has been only partly achieved: the contribution of endothelial cell membranes to transport of water and small, lipid-insoluble molecules needs to be evaluated. The identification of the "small pore" pathway for water and lipid-insoluble molecules with the intercellular junctions still remains questionable. The contributions to total macromolecular transport of junctions, single vesicles (pinocytosis, cytopempsis), chains of vesicles, and fenestrae are not yet known.


Effect of digitalis on left ventricular function in exercising dogs.

The effect of ouabain on left ventricular function in nonfailing hearts was assessed in 14 chronically instrumented dogs during graded treadmill exercise. At rest, ouabain increased the maximum first derivative of the left ventricular pressure (dp/dtmax) and stroke volume by 38% and 16%, respectively. No change occurred in end-diastolic left ventricular diameter or peak systolic left ventricular pressure. During exercise, ouabain reduced maximum running speed and limited the increments in heart rate and systolic pressure but did not alter dp/dtmax, stroke volume, or end-diastolic diameter. When atropine and ouabain were given and severe exercise was performed, there were no differences from controls in running speed, heart rate, dp/dtmax, or other parameters. When ouabain and propranolol were given dp/dtmax increased at rest and during exercise, compared with results with propranolol alone. It is concluded that the inotropic effect of ouabain is negligible during strenuous physical activity because of the presence of high levels of sympathetic stimulation. However, during exercise in the presence of beta-adrenergic blockade, increases in myocardial contractility do occur in response to ouabain.


Effects of therapy on maximal walking time following femoral ligation in the rat.

Maximal walking times at a constant rate of 10 m/min were compared in normal rats, normal rats that had been exercised daily for 6 weeks, and rats that had undergone bilateral femoral artery ligation followed by 6 weeks of either an oral vasodilator, absence of sympathetic impulses to the extremities, cold exposure, or daily exercise. Rats maintained on the vasodilator could walk no farther than untreated, ligated rats. Both chronic cold exposure and sympathectomy significantly increased maximal walking distances of ligated rats and daily exercise increased maximal walking distances 7-fold. Rats that had received 6 weeks of exercise training following femoral artery ligation could walk longer than normal untrained rats; therefore, the increased exercise tolerance could not be explained solely by the restoration of normal large artery conductance by enlargement of collaterals bypassing the femoral occlusion.


Effects of acute, passive hepatic congestion on blood flow and oxygen uptake in the intact liver of the cat.

Raising the hepatic venous pressure experimentally duplicates the type of hepatic congestion seen in many clinical situations including congestive heart failure. Venous pressure was controlled using a hepatic venous long circuit preparation and was raised by 6 cm blood (4.7 mm Hg) or 10 cm (7.8 mm Hg). Total splanchnic blood flow and oxygen uptake were reduced by these maneuvers but hepatic arterial flow was not altered nor was hepatic oxygen uptake. Blood flow in the portal vein decreased to 65 +/- 12% of control and gut oxygen uptake decreased to 60 +/- 14% of control. The data confirm that raised hepatic venous pressure does not produce hepatic edema in spite of massive prolonged fluid filtration across the liver into the peritoneum. In spite of a reduced (to 84 +/- 3% of control) hepatic oxygen delivery, the liver can maintain oxygen uptake (99 +/- 7% of control) by increasing oxygen extraction to appropriate levels. The hepatic artery in these cats were capable of myogenic vasoconstriction in response to altered arterial pressure, but in response to raised venous pressure no tendency for constriction was seen. This is in marked contrast to the vasoconstriction seen in isolated perfused livers where portal blood flow is held constant during the raised venous pressure.


Diffusion permeability of an isolated rete mirabile.

The rete mirabile of the swimbladder of the eeel is a countercurrent exchange organ composed of alternately disposed and venous capillaries. A countercurrent perfusion of these was set up by isolating arterial input and outflow, and venous input and outflow, and perfusing each set of capillaries with oxygenated albumin-containing Krebs-Ringer bicarbonate buffer. Constant arterial infusions containing tracer albumin, inulin, 3-O-methylglucose, urea, and water were begun and tracer concentrations at the outlets of arterial and venous beds were determined. Capillary permeabilities were determined from the resulting steady state values. The method of calculation of permeability values from the data acquired in the rete involves no approximations and appears to yield unequivocal values. For the solutes, the values appear compatible with transcapillary passage by free diffusion. No evidence of increasing restriction (in comparison to the diffuse coefficients) was found over the range of molecular sizes explored. The permeability for labeled water, in relation to the solutes, was too high, and this augmentation was attributed to the larger surface available for its exchange. Despite this larger value, labeled water did not undergo flow-limited exchange. A significant barrier to its distribution is present in this capillary system.


Lack of correlation of plasma norepinephrine and dopamine-beta-hydroxylase in hypertensive and normotensive subjects.

Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) have been determined in over 350 plasma samples from 174 subjects while resting supine (basal sample), standing, or exercising. Although increments in both NE and DBH were found with postural change, the further increase in plasma levels of NE during exertion was not attended by any change in levels of DBH. There was no significant correlation between basal levels of DBH and NE nor was there any correlation in their increments after standing or exercising. DBH activity in plasma of subjects with moderate essential hypertension was not different from that of normotensive subjects. It is concluded that plasma DBH is a poor index of acute sympathetic neuronal activity.


The effect of mannitol following permanent coronary occlusion.

Quantitative comparisons of infarcts 24 hours after ligation of the left anterior descending coronary artery (LAD) via thoracotomy were made in 13 control and 13 dogs treated with i.v. 25% mannitol, 2 ml/min for 4 hours following occlusion. Mannitol increased serum osmolarity by 44+/-4 mOsm/L (mean +/- 1 SE) with hemodynamic effects limited to a small increase in left ventricular dP/dt. Nonperfusible tissue measured by planimetry at 24 hours was similar in both groups (46+/-4% of area defined with dye injected into the distal LAD for control versus 48+/-5% for mannitol treated dogs, P = NS). Creatine phosphokinase activity in infarcted tissues was also similar in both groups. Myocardial blood flows measured with radioactive microspheres were also similar in both groups. Collateral conductance calcultaed from retrograde flow and aortic pressure increased with the 24 hour period by 146+/-23% in the control dogs; in the mannitol treated dogs, collateral increased only 38+/-14% (P less than 0.001). Thus mannitol had no effect on ultimate infarct size. Moreover, mannitol appeared to hinder the development of collateral vessels.


Analysis of left ventricular function from multiple gated acquisition cardiac blood pool imaging. Comparison to contrast angiography.

Global ventricular function was evaluated by both multiple gated cardiac blood pool scans (MUGA) and contrast ventriculograms in a group of 17 patients with suspected coronary artery disease. The contrast ventriculograms were analyzed frame by frame to generate a volume versus time curve for each patient, while the tracer data were analyzed by two methods: 1) the standard method, in which the left ventricle is identified on the end-diastolic frame and the background corrected activity under the region of interest obtained from the entire cardiac cycle, and displayed as a time versus activity curve; and 2) by a semi-automatic method in which the computer applies a threshold detection program to define the ventricular borders, and activity in the chamber at each point in the cardiac cycle is defined after background correction. The tracer data in each patient were analyzed independently by four observers. The tracer data correlated with the contrast data on a point by point basis r = 0.87 for the standard method, and 0.93 for the semi-automatic technique. An F test of variance revealed the semi-automatic method superior to the standard approach (P less than 0.05).


Effect of methylprednisolone upon technetium-99m pyrophosphate assessment myocardial necrosis in the canine countershock model.

Repeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-99m pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P less than 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in Mp dogs, resulting in accelerated urinary excretion of PYP (46.9+/-3.6 vs 35.8+/-2.4 percent injected dose in one hour, P less than 0.01), and reduced blood PYP. Thus MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data.


Congenital mitral stenosis. A review of 20 years' experience.

The clinical course of 38 patients with congenital mitral stenosis (MS) is reviewed. Associated cardiac defects were present in 28 patients, including tetralogy of Fallot in five. In all but one of the eight patients with supravalvar mitral ring (SVR), there were concomitant abnormalities of the mitral valve. Delay in the diagnosis of MS was common. Serial cardiac catheterizations and pulmonary pathologic examination indicated that pulmonary vascular obstructive disease develops during childhood. Mitral valve surgery was performed in 19 of 38 patients: valvotomy alone in eight, excision of SVR in five (two ofwhom also had valvotomy) and mitral valve replacemtnt in seven. Additional non-mitral cardiac surgery was performed in 18 patients. Overall surgical mortality was 49%; mortality for surgery on the mitral valve was 26%. Only patients having mitral valve replacement or with isolated SVR which was then resected became asymptomatic and had normal hemodynamics on postoperative catheterization.


Radiographic assessment of leaflet motion of Gore-Tex laminate trileaflet valves and Hancock xenograft in tricuspid position of dogs.

Six samples of various thicknessess of Gore-Tex compounds were fashioned into trileaflet valves. A radiopaque marker was placed on the center of the free margin of each cusp, and the prostheses were implanted in the tricuspid position of dogs. Two Hancock valves were studied for comparison. Catheterization revealed that the hemodynamic function was normal in all valves tested. High-speed radiography permitted analysis of leaflet movement throughout the cardiac cycle. Of the six Gore-Tex valves, five opened completely. The cusps of these five valves were fabricated from 4, 6, 8, 10, and 12 layers of Gore-Tex film. The remaining valve, which was fabricated from 15 layers of Gore-Tex film, and both porcine xenograft aortic valves did not open completely. We postulate that the laminates of 12 layers or less of Gore-Tex film are suitable for further study to evaluate their potential applicability in trileaflet cardiac valve prostheses.


The evolution of peripartal heart failure in Zaria, Nigeria. Some etiologic factors.

The subsequent course of 173 women with severe congestive heart failure hospitalized within 6 months of delivery has been analyzed after 4 to 7 year follow-up periods. Forty-seven normotensive women and 50 women hypertensive only during the initial 48 hours have little long term morbidity. Thirty-six women with hypertension initially improved, but many are now showing enlarging cardiac silhouettes. Morbidity is increasing in this group. A similar, less severe pattern is developing in 36 women with intermittent hypertension. The uniquely high incidence of this condition in Zaria is associated with several locale factors. These Hausa-Fulani women eat large quantities of a local lake salt, kanwa, for 40 days postpartum. The syndrome is markedly more common in the hot rainy season, when evaporative water loss is less, than in the dry season. The first postpartum days are spent confined to bed in a small heated room. Once or twice daily the new mother is given hot baths with branches which have been dipped in boiling water. The combination of excessive sodium intake and diminished evaporative water excretion seems to precipitate failure in both normotensive and hypertensive patients.


Dose-response relation of diazoxide in children with hypertension.

Diazoxide was administered to sixteen pediatric patients (ages 10 months to 13 years) with secondary forms of hypertension. Admission BP was 178+/-8/130+/-5 mm Hg (mean +/- SEM). Diazoxide was administered rapidly intravenously in doses ranging from 2 to 7.5 mg/kg. A significant (P less than 0.001), linear log dose-response relation was obtained which showed that a 3 mg/kg dose of diazoxide lowered diastolic BP by an average of 30 mm Hg. In five patients reduction of idastolic BP by a single injection of diazoxide was no different than when the same total dose was given as two or three small injections repeated at fifteen to twenty minute intervals. It is concluded that 1) many hypertensive children respons significantly to doses of diazoxide smaller than the usually recommended 5 mg/kg; 2) diazoxide has a significant dose-response relation in hypertensive pediatric patients; and 3) the desired blood pressure response in hypertensive children can be titrated using repeated small injections of diazoxide.