Morphologic changes in age-related maculopathy

Age-related maculopathy (ARM) is a degenerative disorder of the central part of the retina with a rising prevalence in patients 50 years of age and older, and comprises different histopathological changes. The morphologic changes in ARM are described and illustrated with light-microscopical, electron microscopical, and fundus pictures. Furthermore, the most important biochemical data are given. The most prominent aging changes in early stages of ARM are drusen and basal laminar deposit (BLD), both extracellular deposits, that are assumed to be important in the development of ARM. Drusen accumulate within Bruch's membrane, whereas BLD is present between Bruch's membrane and the retinal pigment epithelium. Although the histopathologic characteristics of the deposits are well documented, the chemical composition has only been partly resolved. Biochemical analysis of these deposits is necessary to determine the source of the deposits and to find possible ways to avoid or treat them. The late stages of ARM, geographic atrophy, and neovascular (disciform) degeneration, are called age-related macular degeneration (AMD), and result in severe and irreversible visual impairment. Since there is still no adequate therapy for the majority of people disabled by AMD, and because of the aging population resulting in even more patients with this disease, it is necessary to intensify the research on ARM in order to prevent AMD or find a therapy for it.     

Histopathological changes in rabbit uterus carcinoma after transcatheter arterial embolization using cisplatin

Axenic mass cultivation of Acanthamoeba castellanii in laboratory fermentors (141) yielded after 20 days approximately 3 g cells (wet weight). After a short lag phase amoebal cell numbers increased exponentially to a maximum of 3.5 x 10(5) cells per ml until cell death occurred after 20 days. Optical density and protein concentrations revealed identical patterns. During amoebal growth only 12-19% of the initially added glucose (100 mM) as sole carbon source was used. Large amounts of ammonia (1 g in 10.51 culture volume) were excreted into the medium which subsequently raised the pH from 6.6 to 7.7, and from 6.6 to 6.8 in 2 and 20 mM buffered media, respectively. Growth inhibition and cell death could not be explained by a depletion of glucose or oxygen limitations during growth. The production of ammonia had a growth inhibitory effect, however, the sudden termination of the exponential growth phase and cell death could not be explained by the toxic influence of ammonia only.     

Morphologic changes in the elastic fibers of the temporomandibular joint after experimental disc perforation in the rabbit

PURPOSE: Elastic fibers in the attachment regions of the temporomandibular joint (TMJ) are considered important in the movements of the disc during jaw motion. This study was designed to determine whether there are change in the elastic fibers of the TMJ when the disc is perforated for a long period. MATERIALS AND METHODS: Each TMJ of five rabbits was surgically exposed, and a mediolateral perforation was made in the center of the articulating region of the disc with a scalpel. Five untreated and three sham-operated rabbits were used as controls. The TMJs were removed after 10 months and processed for histochemical demonstration of elastic fibers. RESULTS: Osteoarthritic changes and a significant decrease in number of the elastic fibers in the anterior-inferior attachment and posterior-inferior attachment of the TMJ disc were observed after disc perforation. Conversely, elastic fibers appeared in the fibrous tissue on the resorbed bone of the articular eminence. CONCLUSIONS: Experimental disc perforation changes the distribution and density of the elastic fiber in the TMJ as well as causes osteoarthritis. A knowledge of these facts may improve our understanding of perforation of the disc.     

Superselective arterial catheterization in the rabbit

RATIONALE AND OBJECTIVES: To improve the safety and success of selective and superselective arterial catheterization in the rabbit. METHODS: A 2-F catheter introducer system was devised that consisted of the sheath of an 18-gauge, 5.1-cm sheath needle and a hemostatic valve attached to the hub of the sheath. The system was tested in 14 adult male New Zealand white rabbits with regard to ease of insertion and facilitation of superselective arterial catheterization. RESULTS: The introducer system was easily placed in all rabbits, and no bleeding was seen around the sheath at the puncture site. Preshaped 2-F polyethylene catheters were readily inserted through the assembly and sheath. The valve prevented bleeding from around the catheter, and the side-arm flush tube served as a route for heparinization. The system greatly facilitated the manipulation of 2-F angiographic catheters. CONCLUSION: Use of the introducer system with a 2-F polyethylene angiographic catheter improved the success of selective and superselective arterial catheterization in the rabbit.     

Manifestations of asymmetry during regeneration of microvessels of rabbit ears]

Diabetic pregnant women have many potential reasons to have genital infections such as poor metabolic control and impairement of leucocyte function. Relative immune deficiency exists in pregnancy. This study was designed to test the hypotheses that pregnant patients with insulin-dependent diabetes have a higher rate of ante partum genital infections when compared with a pair-matched control population. Two groups of pregnant women consisting of 23 patients with and 23 without diabetes mellitus, underwent colposcopy and cytology between 16th and 24th week of gestation to detect the presence of human papilloma virus (HPV), Gardnerella vaginalis, Candida albicans and aspecific infections. No significant differences were observed between the two groups.     

"Hitch-hike" grafts for limb salvage in peripheral arterial disease

A technique of arterial reconstruction suitable for patients with extensive arterial occlusions and for previous failed arterial surgery is described. The "hitch-hike" graft consists of a proximal limb of 6-mm velour Dacron prosthesis and a distal limb of autogenous vein. The intermediate prosthesis-to-vein anastomosis is made into an endarterectomized segment of upper popliteal artery. The results in the first 16 limbs are described. Eleven grafts are functioning from 2 to 14 months after operation and 5 of these have functioned for more than 1 year. The advantages of the technique are: long arterial occlusions may be bridged; autogenous vein is used to cross the knee joint; good measured blood flows may be demonstrated at operation; acceptable patency rates may be obtained up to 1 year.     

Morphologic changes in collagen fibers after 830 nm diode laser welding

BACKGROUND AND OBJECTIVE: The mechanism of laser tissue welding is elusive, but collagen transitions are somehow involved. Collagen fiber modifications observed after 830 nm diode laser welding are presented in this study. STUDY DESIGN/MATERIALS AND METHODS: A 830 nm diode laser assisted longitudinal aortorrhaphy was performed on 37 Wistar rats, with shots of 0.5 W in power, 8 sec in duration and 250 W/cm2 in irradiance. Energy utilized ranged from 400-550 J/ mm2 for 1 cm-length of anastomosis. After laser welding, histological modifications in collagen fibers were observed through optic, scanning electron, and electron microscopic examination. RESULTS: After laser welding, collagen fibers lost a proportion of birefringence. Under electron microscope, the different changes in collagen fibers were visualized being either fused, "roped," swollen, or dissolved, surrounded by normal ones situated in the same zone. CONCLUSION: These data suggest that diode laser heating denatured part of the collagenic fibers, and that these morphologic changes play an important role in laser welding.     

Morphologic changes in the thrombus and venous wall in experimental phleobothrombosis and thrombophlebitis

Phlebothrombosis and thrombophlebitis were induced in dogs by percutaneous intraoperative introduction of thrombotic mass, obtained in vivo (20-40 animal blood per 3-4 ml thrombin solution) into jugular vein and studied in postoperative days 1, 3, 5, 7, 10 and 14 through light microscope. The preparations were stained with hematoxylin and eosin and after Hart, Van-Gieson and MSB. Venous intima was established to alter already on the next day following thrombophlebitis modeling. On d 3 and 5 epithelium desquamation and moderate leukocytic infiltration of media between smooth myocytes were found. On d 7 signs of thrombus organization, i.e. invasion of fibroblastic series cells and small capillaries inside it, were demonstrated. Muscular layer and adventitia display leukocytic infiltration. Venous wall thickens due to disorders of blood passage in vasa vasorum. On d 10 the portion of the thrombus attached to the wall was essentially organized. Fibroblasts and capillaries invade inside the thrombus, connective tissue fibres are formed. Sclerotic changes were noted in adventitia. By the end of the 2nd week venous wall showed muscular layer atrophia and sclerosis. Middle portions of the thrombus were involved in organization, canals lined with endothelium are formed in it. In case of thrombophlebitis changes in thrombus and venous wall develop earlier and are more pronounced.     

Morphologic changes in hepatocyte nuclei of streptozotocin (SZ)-induced diabetic mice

Morphological examinations were carried out on hepatocyte nuclei of streptozotocin (SZ)-induced diabetic mice. The area of hepatocyte nuclei in diabetic mice was about two times larger than that in control mice, and the incidence of hepatocytes with intranuclear inclusions was 3.4 +/- 0.2% in diabetic mice and 0% in control mice, respectively. Although the incidence of binuclear hepatocytes was not significantly different between diabetic (14.5 +/- 4.6%) and control mice (16.4 +/- 4.4%), the morphology of the nuclei of binuclear hepatocytes was apparently different between diabetic and control mice. Namely, the nuclei of binuclear hepatocytes of control mice were round and identical in ultrastructural appearance, and they did not differ from those of mononuclear diploid hepatocytes. On the other hand, the nuclei of binuclear hepatocytes of diabetic mice were not identical in distribution pattern of chromatin granules, and they frequently varied in size and showed irregular contours.     

Morphology and function of preserved microvascular arterial grafts: an experimental study in rats

The aim of this study is to examine the morphology and function and small-caliber, arterial grafts after preservation in the University of Wisconsin solution (UW). Rat carotid arteries were stored in UW (n = 10) or in phosphate-buffered saline (PBS) (n = 10) for 1, 3, 7, and 14 days and were examined with light microscopy (LM) and scanning electron microscopy (SEM). Rat aortic preparations were stored in UW or PBS for 1 hour, 24 hours, 72 hours, 7 days, and 14 days and assessed for functional responses (stimulated contraction and endothelium-dependent relaxation). Segments (5 mm) of rat carotid arteries were stored in UW or PBS for 3 days, 7 days, and 14 days and orthotopically implanted as autografts and allografts. No immunosuppressive or anticoagulant agents were used. After 28 days of implantation, the grafts were assessed for patency and excised for LM and SEM. In UW, the endothelial layer remained intact up to 9 days of storage. In PBS, the endothelial layer showed deterioration after 1 day and was completely lost after 3 days. Functional responses were demonstrated to exist for as long as 7 days storage in UW. In PBS, no responses could be evoked after 24 hours storage. Autografts preserved in UW for 3 days (n = 6), 7 days (n = 6), and 14 days (n = 6) showed patency rates of 83.3%, 66.6%, and 66.6%, respectively, whereas patency rates of allografts were 66.6%, 33.3%, and 33.3%, respectively. Autografts stored in PBS for 3 days (n = 6), 7 days (n = 6), and 14 days (n = 6) showed patency rates of 33.3%, 33.3%, and 50%, respectively, whereas patency rates of allografts were 16.7%, 0%, and 33.3%, respectively. The UW preserved autografts showed normal morphology. All other groups showed vessel wall degeneration which in the allograft groups, were accompanied by lymphocellular infiltration. In conclusion, the endothelial layer and vessel wall of arteries are adequately preserved in UW. Functional responses are retained up to 14 days storage in UW, but, are lost after 24 hours storage in PBS. Autograft implantation studies accordingly show good performance of arterial segments preserved in UW, whereas allografts are subject to degradation as a result of rejection.     

The effect of probucol on intimal thickening of autologous vein grafts in hyperlipidemic rabbit

OBJECTIVE: To define whether there is any relation between the iron status of patients with hepatitis C virus (HCV) chronic liver disease and their response to interferon therapy. DESIGN: To evaluate the long-term response to 1 year of interferon therapy with addition of phlebotomies after 3 months of treatment if at that time alanine aminotransferase (ALT) had not normalized in a group of patients with HCV-positive chronic liver disease whose iron status had been characterized. SETTING: A northern Italian hospital. PARTICIPANTS: Fifty-eight anti-HCV-positive patients (four HCV-RNA negative) with biopsy proven chronic hepatitis and no evidence of iron overload as indicated by normal transferrin saturation at the time of enrollment in the study. INTERVENTION: Three times a week intramuscular injection of alpha interferon 3 MU for 1 year with addition of phlebotomies (350 ml/week) till iron depletion if after 3 months of interferon therapy ALT had not normalized. RESULTS: A long-term response was observed in 19 of the 52 patients who completed the treatment, four HCV-RNA negative and 15 positive. The four RNA-negative and seven of the 15 RNA-positive long-term responders had been treated with interferon alone, and the other eight also with phlebotomies. At univariate analysis only HCV genotype, gamma-glutamyltranspeptidase and liver iron concentration were significantly associated with response whereas sinusoidal iron deposition was of borderline significance. No association was found with sex, age, duration of disease, histology, Knodell score, transferrin saturation %, serum ferritin, hepatocytic iron score, and portal iron score. HCV-RNA serum levels, measured in 29 patients, did not correlate with response. At multivariate analysis liver iron concentration was still significant and one unit reduction of liver iron concentration (natural logarithm transformed) was associated with 2.95 odds ratio of response. CONCLUSION: These results indicate that iron in the liver is more closely related to response to interferon than the other variables considered, including HCV characteristics.     

Admittance tympanometry in otosclerotic ears

Twenty-eight surgically confirmed otosclerotic ears were evaluated to determine whether tympanometric admittance measurements could differentiate otosclerosis from a normal population. Subjects were tympanometrically measured at test conditions B220, B660, G220 and G660 Hz. When comparing mean curve peak amplitude to normative standards, 20 ears showed significantly low admittance tympanograms. Further investigation revealed no significant differences in curve width or pressure of the curve peak. Of the remaining eight otosclerotic ears, all produced diphasic "W"-notched tympanometric configurations. Diagnostic implications and physiological hypothesis are discussed.     

Endothelial F-actin changes in the alkali burned rabbit cornea

The healing mechanism of corneal endothelium after alkali burn was not completely understood. Rabbit cornea was burned with 1N sodium hydxoside for 1 minute. Endothelial F-actin was stained with NBD-phallacidin in regular sequence to find out the details of endothelial healing after alkali burn. F-actin was completely destroyed leaving a sharp margin against the unaffected area 1 hour after the burn. In the 3, 5 and 7 day specimens, highly active F-actin reactions were noted at the wound margin. New multiple F-actin layers, arising from the intact endothelium near the wound margin, were noted in the 9 day specimen. In the 8 1/2 month specimen, the endothelial defected area was covered by large primitive cells, each of which showed F-actin fiber bundles in the cytoplasm with a large nuclear shadow. Nearly all of the large primitive cells showed F-actin fibers arranged in shapes of cell junctions. Twelve months after the burn, endothelial defects were not found. Nearly all of the endothelial cells were normal in size and shape except for some mushroom-like projections toward the anterior chamber in some areas. Nineteen months after the burn, the endothelial cells were normal. Endothelial wound healing process can be continued even 1 year after the alkali burn in rabbit cornea.     

Molecular and cellular changes in vein grafts: influence of pulsatile stretch

Sudden cardiac death is frequent in patients with dilated cardiomyopathy. To assess the risk of an arrhythmic event is still difficult. Here the analysis of the heart rate variability offers new possibilities. METHOD: 25 patients (18 males, 7 females, age 53 +/- 9 yrs) with dilated cardiomyopathy were included in the study. Analysis of heart rate variability assessed by time- and frequency-domain measures was determined from Holter recording. The mean follow-up was 18 +/- 5 months. RESULTS: 6 patients died (5 of sudden cardiac death, 1 of heart failure), 1 patient with an implanted defibrillator received an adequate shock. Parameters influenced by low- and mid-frequent oscillations of the heart rate were significantly lower in patients who died suddenly or had adequate shocks. The best predictive parameter was the s.d.RR: all patients with an s.d.RR < 50 ms had lethal arrhythmias whereas the s.d.RR of the surviving patients was > or = 50 ms. No significant difference was found or high frequency parameters, which are mainly influenced by parasympathetic activity. CONCLUSION: The analysis of heart rate variability is of prognostic relevance in patients with dilated cardiomyopathy. Especially the s.d.RR is able to identify patients with a high risk of a sudden cardiac death.     

Internal iliac arterial infusion chemotherapy for rabbit invasive bladder cancer

Eleven patients with T4 breast cancer received induction intraarterial chemotherapy (IACT) as the first step in multidisciplinary therapy. The IACT agents (epirubicin and mitomycin C), were delivered weekly in the outpatient department by bolus injection through an implantable port-catheter system. A modified technique of port-catheter system implantation was used. The precise localization of the catheter was dually confirmed by angiography and dye test. The effectiveness of the treatment was evaluated by clinical appearance, image study, and microscopic examination. A 91% response rate was obtained, and the lesions were resectable in < or = 8 weeks. No obvious systemic toxicity resulted from the IACT. Our results show that weekly IACT by bolus injection through a port-catheter system for treating locally advanced T4 breast cancer is feasible and efficacious.     

Morphologic and metabolic changes in rat osteoblast cultures during the dark reaction with 8-methoxypsoralen

The dark reaction of 8-methoxypsoralen (8-MOP) with cultured rat osteoblasts did not cause significant changes in cellular replication rates or in the synthesis of RNA and proteins. Microscopic examination, however, revealed that the dark reaction resulted in massive accumulation of perinuclear lipids and in the statistically significant enhancement of alkaline phosphatase activity. A sharp, and statistically significant, upsurge of lipid synthesis in osteoblasts preceded microscopically detectable accumulation of lipids and occurred only during the initial, but not during the subsequent stages of the dark reaction. These results suggest that in the course of the dark reaction the plasma membrane of osteoblasts is a target of psoralen.     

Morphologic changes in the urinary bladder of mice induced by metabolites of tryptophan and tyrosine

45-day-old 229 mice of lines C57Bl and CC57Br were injected subcutaneously water solutions of tryptophan and thyrosine metabolites 2.5 mg twice a week, the total dosage being 45-50 mg per mouse. For the control mice of the same line were taken. Within the period from 3.5 to 19 months following injection of the metabolites in the urinary bladder of animals, there were observed focal proliferates of the epithelium not infrequently with its atypism, and also lymphoid infiltration of submucous and muscle layers, reticulosarcomas, papillomas, precancerous conditions and cancer. The question of the importance of endogenous blastomogenic substances in the development of "spontaneous" tumors of the urinary bladder in man is discussed.     

Clinical experience with expanded polytetrafluoroethylene (Gore-Tex) grafts for femoropopliteal arterial bypass

Thirty-seven grafts of expanded polytetrafluoroethylene were implanted in 28 patients in whom autogeneous saphenous vein was not available, either for symptoms of severe claudication or limb salvage. The length of follow-up ranges from 8 to 28 months . The patency rate is 86.9 percent for the patients with severe claudication and 71.4 percent in the limb salvage group; the overall patency rate is 81 percent. We believe that expanded polytetrafluoroethylene is a good prosthetic substitute when autogenous vein is unavailable.