U.N. Riede

Experimental use of an albumin-glutaraldehyde tissue adhesive for sealing pulmonary parenchyma and bronchial anastomoses.

OBJECTIVE Despite advanced surgical techniques, major complications of bronchial anastomoses and parenchymal repair, including early leak, fistula formation and granulations still occur. The purpose of this study was to test the performance of an albumin-glutaraldehyde tissue adhesive (BioGlue), CryoLife Inc., Kennesaw, GA) as a sealant for bronchial anastomoses and parenchyma lesions. METHODS Twenty-four sheep were split into two surgical groups. The first group consisted of six control sheep receiving standard sutured bronchial anastomosis with a 4-week end-point. The second group included 18 sheep receiving both a bronchial anastomosis and parenchymal defect repair using the adhesive with 2, 4, and 12 week end-point. Histopathologic evaluation was conducted at the study end-points. RESULTS Bronchial anastomosis and parenchymal tissue repair can be sealed successfully against air leakage with adhesive. Macroscopic evaluation revealed a tight closure of the anastomosis and parenchyma defect in all postoperative stages, initially by the adhesive layer, and later by connective tissue. On microscopic examination, an inflammatory tissue response consisting of polymorphonuclear neutrophils, macrophages, granulation tissue and foreign body giant cells were found surrounding the glued area after 2 weeks. After 4 weeks the tissue response presented a granulomatous character. No granulomatous or foreign body reaction was present in the hand sutured group. After 12 weeks few remnants of adhesive surrounded by fibrous scar tissue were detectable in bronchial anastomosis and parenchymal repair. Healing was not considerably complicated by foreign body reaction or tissue granulation. CONCLUSION This study supports BioGlue to be effective as an adjunct in sealing bronchial anastomosis and lung parenchyma defects in sheep, with minimal secondary healing disruptions such as granuloma formation. The results of this study indicate that the use of BioGlue in human pulmonary surgery should be effective.

The pulmonary air-blood barrier of human shock lungs (a clinical, ultrastructural and morphometric study).

Interstitial edema in the alveolar septa is the first morphologically recognisable change to be observed in cases of shock. It is brought about by the altered function of the membranes of the damaged epithelium and endothelium in the alveolar wall. At the same time there is an impairment of gaseous exchange, which is rendered more difficult by the exudative process in the interstitium. Pari passu with these events there is injury to the cells of both the alveolar epithelium and the alveolar capillary endothelium. Both these processes are still reversible. The point of irreversibility appears to be reached--so far as time is concerned--at the end of the first week, after which the injurious effects on the cell are established, since the thin alveolar wall necessary for the exchange of gases becomes overgrown with bulky alveocytes (Tpye II), and the fibroblasts in thealveolar interstitium push the capillaries away from the surface of the alveolus. In most of the advanced cases of shock this process of thickening of the alveolar wall exceeds the critical value, and respiratory exchange is so impaired that satisfactory functioning of the lungs is no longer possible.

Morphologic development of human shock lung.

In the initial phase of shock, edema spreads throughout the alveolar interstitium even before injury occurs in the alveolar epithelium and endothelium. The endothelium and the epithelium are damaged only subsequently, causing reduction in the average barrier thickness of the epithelium and the endothelium. A point of irreversibility is reached by the end of the first week. While early cell regeneration may be observed within the alveolar endothelium and epithelium, proliferation of fibroblasts and fibrosis of the alveolar wall occur in addition to edema which spreads within the interstitium. This widening of the gas exchange barrier may be considered as the anatomic substrate of respiratory insufficiency induced by shock. This enlargement continues up to the moment when thickening of the alveoli impedes satisfactory functioning of the lung, and, as consequence, threatens the life of the patient.

Fructose Induced Glycogenosis IV. Morphometric Analysis of Organelle Regeneration in Rat Liver Cells During the Recovery Phase Following an Initial Loading with Fructose

Abstract Introduction: The intake of fructose has been shown to stimulate the SER and reduce the RER in the rat liver cell. After feeding with fructose for seven days glycogenosis is found in the cells of the liver, and this is accompanied by a hypoplasia of the organelles - especially the endoplasmic reticulum. It was therefore thought to be of interest to analyse the regenerating organelles morphometrically a short time after the return to a normal diet. Material and methods: A 60% solution of fructose in water was given as the sole diet to rats (body weight 180 g). Controls had unrestricted access to an Altromin-R standard diet and drinking water. After fructose overloading for 7 days the experimental animals were returned to the control diet for three days, and the hepatic tissue analysed morphometrically according to the method described by Weibel. Results and discussion: After 7 days administration of a 60% solution of fructose in water as the only source of food and drink, a massive storage of glycogen is found in the hepatocytes, accompanied by a hypoplasia of the organelles. Three days return to a normal diet of Altromin-R standard food is sufficient to bring about regeneration of these cytoplasmic organelles. The enormous fructose induced glycogen store is again reduced to normal size with the development of lysosomal hyperplasia. Following this, phosphorylation occurs, together with a hyaloplasmatic reduction in glycogen rather than a lysosomal glycogenolysis. Oedema of the nucleus and cytoplasm disappears, and the mitochondrial hypoplasia is replaced by hyperplasia. Hypoplasia of the peroxisomes is followed by a hyperplasia, in which the micrope roxisomes play the major part. The surface area and volume of the RER return to normal under the influence of the normal Altromin-R diet, and this is accompanied by an increase in the number and volume of the nucleoli, suggesting a return to protein synthesis. On the other hand, the three days of normal feeding are sufficient to bring the surface area of the SER within normal limits again. However, it is worth to remarking that the pattern of distribution of glucose-6-phosphatase activity returns to normal once again, since it is well known that this enzyme is a marker enzyme of the endoplasmic reticulum.

Increased growth-stimulating activity of thoracic lymph after hemorrhagic shock

Summary During the late phase of shock, which must be regarded as an acute generalized circulatory failure, pronounced cell proliferation and increasing fibrosis is seen in the pulmonary interstitial space. Cell proliferation and fibrosis result in irreversible pulmonary changes and frequently cause death. Fibroblasts of different origin are stimulated in vitro by the thoracic lymph of pigs to produce increased proliferation after shock (Mittermayer et al., 1978). The question arises as to whether or not this stimulated growth is organ-specific and whether this phenomenon can also be demonstrated in vivo. The present study investigates the effect of thoracic lymph of the pig after a hemorrhagic shock which stimulates cell proliferation in vivo. Hemorrhagic shock was induced in domestic pigs by removal of 40-50% of the blood volume for 3 hours. Thoracic lymph which had been obtained before the beginning of the experiments, at the end of the shock phase, and 2-3 hours following retransfusion, was quick-frozen and lyophilized. The mitotic rate and DNA synthesis (3HTdR-index) were used as parameters of cell proliferation in various cell populations of the rat following intraperitoneal injection of lymph powder dissolved in saline solution. Application of thoracic pig lymph harvested before the shock-inducing event does not influence the mitotic rate as compared either to bovine serum albumin or to physiological saline solution. Pig lymph obtained during the shock-inducing event produces a significantly increased mitotic rate in the squamous epithelium of the stomach, which is even more increased by pig lymph after the shock-inducing event. This effect is most significant in the squamous epithelium of the stomach and in the alveolar cells of the lung. The mitotic rate of the glandular epithelium in the ileum is only slightly increased. DNS synthesis (3HTdR-incorporation) is significantly increased in the squamous epithelium of the stomach and the mouth as well as in the alveolar and endothelial cells of the lung. The DNA synthesis in the cells of the ileum mucosa is increased only insignificantly. As for the mitotic rate, DNA synthesis following application of pig lymph obtained during the shock-phase shows a significant increase only in the squamous epithelium of the stomach. Thoracic pig lymph from normal animals does not influence DNA synthesis. The effect of pig lymph following the shock-inducing event reveals the highest increase of cell proliferation in different cell populations, and is therefore not organ-specific. Aggregates of thrombocytes are most likely at least one possible source for the release of these growth factors.

Cytophotometric Measurements of the DNA in Hodgkin Lymphomas and Non-Hodgkin Lymphomas*

In smear preparation of lymph nodes excised from 36 patients with a malignant lymphoma the DNA content was estimated in different tumor cells following Feulgen staining by means of quantitative cytophotometric measurements. The tumors investigated included 11 Hodgkin lymphomas and various types of Non-Hodgkin lymphomas (altogether 25). Whereas the small lymphoid cells found in Hodgkin lymphomas show a diploid DNA content with a wide scattering, in the large mononuclear reticular cells (Hodgkin cells) as well as in Sternbergs giant cells only aneuploid DNA values are seen lying in the hyperdiploid, hypertetraploid and hyperoctoploid regions. DNA stemlines are found in the aneuploid regions, but in some cases they are missing. This indicates that we are dealing with malignant tumor cells. In Non-Hodgkin lymphomas with a low grade of malignancy (centrocytic-centroblastic lymphoma, centrocytic lymphoma, CLL) an aneuploid DNA content is found particularly in the large cells (centroblasts, lymphoblasts) with or without a DNA stemline. These cells must be considered as primary malignant tumor cells. In the immunoblastic lymphoma of high malignancy only aneuploid tumor cells are present showing a particularly intense DNA content in the large immunoblasts, whereas a DNA stemline is usually missing. The range of aneuploid values, the number of polyploid tumor cells and the presence or absence of a DNA stemline are important criterions in determining the degree of malignancy. By means of cytophotometric measurements of the DNA content in the tumor cells of malignant lymphomas it is possible to assertain the degree of malignancy and to establish an objective prognosis.

Pathologie und Pathophysiologie des Kreislaufschocks mit besonderer Berücksichtigung der Schocklunge

ZusammenfassungDer Kreislaufschock stellt ein akutes generalisiertes Versagen des Kreislaufs insbesondere der Kreislaufperipherie mit oder ohne Blutdruckabfall und Gewebsschädigung durch Sauerstoffmangel dar. Kausalpathogenetisch sind Sauerstoffmangel, Endotoxin, Komplement und vasoaktive Amine in einem noch nicht vollständig bekannten Zusammenspiel mit einer Mikrothrombose verantwortlich zu machen. Bezüglich der Organmanifestation des Schocks steht die Schocklunge als Krankheitsbild der modernen Intensivmedizin im Vordergrund, die sich klinisch als akute respiratorische Insuffizienz mit einer Perfusions- und einer Diffusionsstörung für Sauerstoff, einer vermehrten Totraumventilation, einem vermehrten Shunt-Volumen und einer vermehrten Atmungsarbeit äußert. Der pathologische Vorgang der Schocklunge verläuft biphasisch, beginnt mit einer exsudativen Alveolitis und endet in einer alveolären Fibrose, welche therapeutisch kaum mehr zu beherrschen ist. Diagnostisch und für das weitere therapeutische Procedere entscheidend ist die Frühphase der Schocklunge sowie die exsudative Alveolitis. Von ihrer Eindämmung hängt das weitere Schicksal des Patienten ab.AbstractThe circulatory shock presents an acute generalized failure of the circulation, in particular of the lesser peripheral circulation, and may possibly but not necessarily be accompanied by a decrease in blood pressure and damage to the tissue due to a lack of oxygen. The main question concerning the causal pathogenesis of shock is still unsettled, but an interaction between a lack of oxygen as well as of other factors, like endotoxin, complements and vasoactive amines, and the presence of a microthrombosis must be held responsible for the appearance of this condition. In modern intensive medicine the lung must be considered as the preferential area for the manifestation of shock. The clinical picture of shock lung may be described as acute respiratory deficiency accompanied by an impaired diffusion of oxygen, an increase in dead-space ventilation together with an increased shunt volume and intensified respiratory activity. The pathology of shock lung shows two phases and has its onset in exudative alveolitis followed by alveolar fibrosis which can hardly be controlled by therapy. The early phase of shock lung manifesting itself by exudative alveolitis is decisive with regard to diagnosis and further therapeutic measurements. If the condition can be brought under control at this stage there is a chance that the patient may survive.The circulatory and acute generalized failure of the circulation, in particular of the lesser peripheral circulation, and may possibly but not necessarily be accompanied by a decrease in blood pressure and damage to the tissue due to a lack of oxygen. The main question concerning the causal pathogenesis of shock is still unsettled, but an interaction between a lack of oxygen as well as of other factors, like endotoxin, complements and vasoactive amines, and the presence of a microthrombosis must be held responsible for the appearance of this condition. In modern intensive medicine the lung must be considered as the preferential area for the manifestation of shock. The clinical picture of shock lung may be described as acute respiratory deficiency accompanied by an impaired diffusion of oxygen, an increase in dead-space ventilation together with an increased shunt volume and intensified respiratory activity. The pathology of shock lung shows two phases and has its onset in exudative alveolitis followed by alveolar fibrosis which can be hardly be controlled by therapy. The early phase of shock lung manifesting itself by exudative alveolitis is decisive with regard to diagnosis and further therapeutic measurements. If the condition can be brought under control at this stage there is a chance that the patient may survive.

Reaction patterns of cell organelles in vitamin B6 deficiency: Ultrastructural-morphometric analysis of the liver parenchymal cell

Under the influence of seven weeks of vitamin B6-free nutrition, the hepatocyte single volume is diminished in the face of an unchanged nuclear single volume, posing the question of whether there is proportional atrophy of all cell organelles or single organelle atrophy with counter-regulatory hyperplasia in other cellular compartments. The nucleoli hypertrophy, as the result of segregation and protein synthesis inhibition. The rough endoplasmic reticulum experiences hypoplasia, but the ultrastructural-morphometric analysis does not determine which metabolic steps are attacked. By contrast one observes hyperplasia in the smooth endoplasmic reticulum, which may be regarded as a counter-regulatory mechanism to the choking of protein synthesis. As with the rough endoplasmic reticulum, the mitochondria also show hypoplasia. This is due to the dependency of the mitochondria upon the endoplasmic protein synthesis. The disturbed functional output of the endoplasmic reticulum is seen in the reduced number of orthoperoxisomes as well. The Golgi apparatus experiences hypoplasia as a result of B6 hypovitaminosis, and this must be considered in the context of fatty change in the liver.

Cardiac Echinococcosis with Pulmonary Embolism

The case of a 37-year-old Italian man with cardiac involvement by echinococcus granulosus is presented. The patient showed symptoms of severe cardiac failure and died suddenly on cardiorespiratory arrest. Autopsy revealed a ruptured parent hydatid cyst attached to the right ventricular wall and massive embolism, by daughter cysts, of the right branch of the pulmonary artery. Although cardiac involvement is present in only 0.5% to 3% of all cases of echinococcal disease, it represents a very serious clinical condition which is followed by sudden death in 29% of the cases of ruptured cysts.

Quantitativ-Logische Homologien in der Diagnostischen Elektronenmikroskopie: Anwendung der Morphometrie and der mathematischen Logik am Beispiel der GM1-Gangliosidose

Abstract The multiplicity of morphometric investigations has led to an explosive growth in data. The following paper lays the foundation for a “recycling” of these data, using a quantitative organelle pathology of growth disorders expressed in terms of symbolic logic, in which nine pathologic states suffice to describe the entire rang of cellular injury. These nine pathologic states in turn correspond to five morphologic states which give the mean change in oranelle size. These nine pathologic and five morphologic states make it possible to expresss the average ultrastructural change in a cell during cellular injury which is both easy to visualize and unambiguous. The rule of homology as introduced in the field of pathology by W. Doerr has proved to be very prosperous in helping to elucidate incomprehensible relationships. The present study tries to show that this also holds true of quantitative organelle pathology. The types of homology occurring in the ergastoplasmic-mitochondrial-peroxisomal system reveal the evidence of existing interactions that will only be determined by means of symbolic logic. These homology types allow to draw conclusions regarding the capacity of the cell to adapt itself and the extent of the cellular injury produced as shown by the example given of GM 1 — gangliosidosis type I. In addition, these homology types as determined by the method of mathematical logics may serve as a suitable model for the pathological anatomy of the human.