Amiodarone-associated changes in human neutrophils.

Amiodarone and its major metabolite, desethylamiodarone, were measured in the plasma, white blood cells (WBCs) and red blood cells (RBCs) of 14 patients receiving chronic amiodarone therapy. The mean plasma concentrations (+/- standard error of the mean) of amiodarone and desethylamiodarone were 2.4 +/- 0.6 and 1.6 +/- 0.4 microgram/ml, respectively. The drug level in the WBCs was 62 +/- 12 micrograms/g protein during the early loading phase and 106 +/- 33 micrograms/g protein during maintenance phase of amiodarone therapy. Desethylamiodarone concentration in the WBCs was 42 +/- 18 and 190 +/- 33 micrograms/g protein during the loading and maintenance phases, respectively. Although a trend in WBC to plasma concentration was seen, there was no linear correlation between these levels. In 1 patient with severe neuropathy, biopsy of the nerve and muscle showed high concentrations of both amiodarone and desethylamiodarone. Although there was a decrease in tissue drug levels, proportionately high tissue:plasma drug levels were detected at the time of necropsy approximately 6.5 months after amiodarone was discontinued in this patient. Neutrophils from all patients receiving chronic amiodarone therapy showed multiple myelin-like polymorphic inclusion bodies (onionoid bodies) upon electron microscopic examination. Our observations suggest that WBC drug concentrations and electron microscopic changes may provide a means of correlating tissue concentrations and of following patients receiving chronic amiodarone therapy.

Evidence of remodeling in dura mater cardiac valves.

Subcellular changes in 12 dura mater cardiac valves (in the mitral or aortic position) surgically removed after 23 to 108 months of implantation owing to calcification, rupture, or endocarditis show signs of a remodeling process. Significant morphologic changes in the connective tissue fiber matrices and cell populations were noted in the recovered valvular leaflets. Macrophages were found within electronlucent (cleared-out) areas, and they seemed to play an essential role in the remodeling process by ingesting and digesting selected connective tissue components. Fibroblasts found within these "rebuilding" areas in the dura mater tissue possessed small cytoplasmic vesicles (65 nm in diameter) being extruded from the cell. Evidence of early collagen formation was also found in association with both peripheral filaments and peripheral condensations, as well as within the connective tissue matrices surrounding the cellular elements, where electron dense amorphous material was observed. In conclusion, the long-term durability of dura mater bioprosthetic cardiac valves may be directly related to (1) glycerin stabilization and preservation of the collagen fibers, (2) the viability of the fibroblasts and macrophages within the implanted valves, and (3) the unique morphology and fine structure of the double-layered dura mater encephali. We hypothesize that the fibroblasts or myofibroblast-like cells found within the implanted leaflets, no matter what their origin, are capable of giving form and organization to the early developing connective tissue.

Microscopic study of normal parietal pericardium and unimplanted Puig-Zerbini pericardial valvular heterografts.

This investigation used light microscopy and transmission and scanning electron microscopy to study native human and bovine parietal pericardium, glutaraldehyde-fixed bovine pericardial patch-grafts, and bovine pericardial cusps of unimplanted Incor or Puig - Zerbini heart valves. The primary objective was to obtain a data base for the future evaluation of postimplantation structural alteration in this valve and in other cardiac valvular bioprostheses constructed of pericardium. The mesothelial cell layer in normal pericardium was best preserved in the bovine tissue. In both bovine patch-grafts and Puig - Zerbini valvular cusps, the serosal surface usually was completely devoid of mesothelial cells and revealed an underlying, finely fibrillar basal lamina. The fibrosa varied in thickness and organization, both within and between the two species, but similar nervous, vascular, and connective tissue components were observed in each. The epipericardial surface was smoother, had fewer elastic fibers, and possessed more surface cells in the human tissue than in the bovine tissue. No evidence of significant tissue degeneration or remodeling was noted in either the stored patch-grafts or heart valves when compared with control bovine and human pericardial tissue layers.

Unusual arrangement of agranular endoplasmic reticulum in the interstitial cells of the cat ovary.

An unusual arrangement of agranular endoplasmic reticulum in the interstitial cells of the cat ovary is described. The structural unit of this arrangement in cross section consists of five membranous sacs (800 to 900 A long and 250 to 350 A wide) radially coverging toward a microtubule. The sacs are separated from each other by three angles of 60 degrees and two of 90 degrees. In longitudinal section, the sacs appear to be long parallel cisternae. The geometric, radial arrangement seems to arise from a gradual incurvation and convergence of parallel units in these membranes. The microtubules may act as guides for the polarization and resulting unusual arrangement of the membranes. The purpose of such polarization may be related to a change from protein to steriod synthesis in these cells.

The development of rabbit ovarian follicles following copulation.

The morphologic development of rabbit ovarian follicles was studied by means of light and electron microscopy 0, 2, 4, 6, 8, and 10 hours after copulation. The progressive changes at the apex of the follicle included extensive edema, hyperemia, and rupture of blood vessels, and then rupture of the follicular wall. Ovulation occurred when the cohesive forces in the cellular layers of the follicular apex became less than the physical forces within the follicle. Most of the morphologic changes in the follicle as it approached ovulation could be related to the effects of locally produced estrogens.

Posterior gastric artery and its significance as seen in angiograms.

The posterior gastric artery was detected angiographically in 46 or 100 patients (46 percent). The importance of radiologic detection of the presence or absence of this artery is emphasized, especially in surgical procedures related to the stomach and immediately adjacent structures.

Intestinal transit time is delayed by artificial sphincters after massive enterectomy in dogs.

Artificial sphincters were created in three groups of dogs after the resection of 87.5 percent of the intestine in each animal. Intestinal transit time was measured after 6 weeks by observing the passage of a radiopaque medium through the animals' intestinal tracts. No statistically significant differences were found between the intestinal transit times of dogs with one artificial sphincter and control animals. In dogs with two artificial sphincters there was a delay in the radiologically monitored intestinal transit time that was statistically significant compared with that of the control group.

History of the pancreas.

The pancreas was generally ignored in antiquity, both as an organ and as a seat of disease. The first description of the pancreas is attributed to Herophilus. It was in the 17th century that the main duct of the organ was described and its significance demonstrated. At that time, Brunner thought that the pancreas was not essential to digestion, and he failed to associate the pancreas with diabetes. Claude Bernard discovered the function of the pancreas in digestion. In 1922, Banting and Best obtained isletin and demonstrated the capacity of the substance to cause a dog to recover from diabetic coma. In 1889, Reginald Fitz firmly established pancreatitis as a disease entity. In 1927, the first case of hyperinsulinism due to a tumor of the islet cells was reported. Twenty-eight years later, Zollinger and Ellison described two patients with unusually severe peptic ulcer disease, both of whom had noninsulin-secreting tumors of the pancreatic islets. Subsequently, gastrin was isolated as the hormone responsible for this syndrome. In March 1940, Dr. O. Whipple performed the first recorded one-stage pancreaticoduodenectomy. Much progress has been made since then and today transplantation of isolated islets and portions of whole pancreas is a reality.

Artificial sphincters as surgical treatment for experimental massive resection of small intestine.

A modification of the technique of Schiller, DiDio, and Anderson was adopted by extending removal of the longitudinal layer of the muscular coat to the entire perimeter of a segment of the small intestine in dogs, resulting in the construction of artificial sphincters, to assist animals undergoing enterectomy. The creation of one or two artificial sphincters prolonged the survival of dogs undergoing massive resection of the small intestine (87.5 percent of the total length).

Microfilaments in granulosa cells of rabbit ovary: immunological and ultrastructural observations.

The present observations demonstrated that the granulosa cells of developing follicles in the rabbit ovary bind antimyosin-like antibodies (AMA). The same granulosa cells studied with the electron microscope showed bundles of microfilaments in the cortical areas of the cytoplasm and within microvilli and large cellular evaginations. The immunochemical and ultrastructural results suggest that the ovarian follicles are not passive organs, but, containing contractile granulosa cells, are capable of producing "in vivo" discrete movements.

Anatomical variations of the human suprarenal arteries.

This is on anatomical study of the suprarenal arteries and their variations in 30 cadavers aimed at providing in a subsequent article the anatomical basis of arterial segments of the gland. The suprarenal glands were supplied by 3 main groups of suprarenal arteries: superior, middle and inferior. Only the superior and the inferior groups were present in all cases, since the middle vessels appeared in only 93.3% +/- 4.6 of the cases. The superior group included on each side 4 arteries in males and 5 in females; the middle group presented only 1 artery on each side in both males and females, and the inferior group exhibited on each side 2 arteries in males and 1 artery in females. The most variable group was the middle one, the aortic origin being the most frequent but with a relatively low incidence (53.3% +/- 9.1 on the right and 46.7% +/- 9.1 on the left). The superior group originated from the posterior branch of the ipsilateral inferior phrenic artery in 83.3% +/- 6.8 on the right and 80% +/- 7.3 on the left. The arteries of the inferior group were branches of the ipsilateral renal artery in 70% +/- 8.4 on the right and 50% +/- 9.1 on the left. The origin of the middle suprarenal arteries from the trunk of the inferior phrenic artery on both sides (26.7% +/- 8.1 on the right and 36.7% +/- 8.8 on the left) should be considered relevant. The anatomical findings warrant a further investigation for the identification, illustration and nomenclature of arterial anatomicosurgical segments.

Anatomical and surgical aspects of splenic segmentectomies.

Based upon the anatomicosurgical segments of the spleen, suggested by DiDio and demonstrated in cadavers, classified and named by Neder (1958) and Zappalá (1958, 1959, 1963), the normal segmental organization was anatomically and radiologically confirmed in 51 human spleens, after studying corrosion casts and radiograms of intraparenchymal vessels (Christo, 1959 a, b, 1960, 1962, 1963, 1993). From 1958 to 1965, pioneer segmental resections were performed successfully in 34 dogs and in 9 patients to safely remove traumatic injured splenic segments. At the same time, the overwhelming postsplenectomy infection (OPSI) became well identified. Consequently, to save normally functioning splenic parenchyma became the most important issue in the management of splenic injuries. The anatomical basis for partial splenectomy and splenic segmentectomy is discussed. The term "splenorrhaphy" was employed to designate all conservative or parenchyma saving operations of spleen based upon its vascular supply: from topical packings to splenic sutures including "cappings" and partial splenectomies. From analysis of 38 consecutive reports in 20 years, covering 4,076 patients, it was concluded that "splenorrhaphies" had been electively employed in 46% of the injuries and partial splenectomies were identified in 8.6% of these surgical interventions. However, the critical minimal mass of splenic tissue to be preserved after partial splenectomies is still to be defined. Postoperative complications directly related to "splenorrhaphies" are rare. Uncommonly performed after splenectomies, the heterotopical splenic autotransplantation has presented dubious results. Trials with nonoperative management of splenic blunt trauma injuries have been safer among children, whose spleens are predominantly transversally disrupted and have a higher relationship "capsular resistance/parenchymal bulk". Splenectomies have been most frequently the ultimate result of delayed laparotomy and underlying risks of growing blood requirements may surpass the advantages of preventing OPSI.

Endoscopic study of the ileal papilla in a normal case and in patients under several pathological conditions.

The ileal protrusion into the lumen of the large intestine was studied in 9 patients (8 adults and 1 girl), 6 females and 3 males, all Brazilians and Caucasians. One of the patients resulted to have no disease, whereas in the others was confirmed the suspected diverticulosis, non specific ulcerative colitis, polyposis, regional ileitis or tuberculosis. In all cases the papillary and bilabial types of the termination of the ileum was documented by endoscopic photography, justifying the change of the expression "Bauhin's ileocecal valve" to that of "eminentia ilealis". Even in cases (one with regional ileitis and the other with tuberculosis) in which the disease altered the eminentia ilealis, it was possible to recognize the ileal papilla. Endoscopy confirmed direct, in vivo observations of ileal papilla, excluding the influence of the surgical procedure (incision and exteriorization in cases of cecostomy) in the morphological aspect of the normal eminentia ilealis.

Morphology of the swine ileum terminale.

The morphology of the terminal ileum was studied in 33 male adult pigs of unknown breed. The ileum ended in the cecocolic junction at an acute angle to the cecum. The terminal ileum displayed a cylindrical form (63.6% +/- 8.4 of the cases) more frequently than an ampullary (21.2% +/- 7.1) and/or an infundibular form (15.2% +/- 6.2). The ampullary form is not related to the quadrupedal position of the animal, but is related to the functional phase of the intestine at the time of death. In the mucous tunica of the terminal ileum, longitudinal folds and aggregated lymphoid nodules appeared concentrated along the antimesenteric border.

Myocardial bridges over coronary arteries in Cercopithecus.

The presence of myocardial bridges over the coronary arteries has been studied in 29 monkey (Cercopithecus aethiops) hearts. The great resemblance between the Cercopithecus subepicardial arterial net with the corresponding one in humans has been revealed. There is a high incidence (83%) of myocardial bridges only over the ventricular branches of both coronary arteries. Myocardial bridges are usually (90%) located over the left coronary artery branches, and the left anterior interventricular branch is the most frequently (69%) overbridged vessel. The bridges are always single over the vessel examined and their length varies from 0.5 mm to 31.6 mm. No statistically significant sexual difference in myocardial bridges distribution is reported.

The prostate in pregnant and non-pregnant Praomys (Mastomys) Natalensis at the subcellular level.

The prostate of the pregnant Praomys appears more active than that of the non-pregnant Praomys. At the light microscopic level, the most obvious features are heightening of secretory cells and increased secretory product in acinar lumina. Apparent at the electron microscopic level are an increase and dilation of the rough endoplasmic reticulum, numerous scattered secretion granules, and a dilated Golgi apparatus. Therefore, stimulation of the gland is evident upon cytological evaluation and this increased activity may be due to the direct or indirect effects of androgenic stimulation.

Subcellular organization of the placenta in the Atlantic sharpnose shark, Rhizoprionodon terraenovae.

The Atlantic sharpnose shark, Rhizoprionodon terraenovae, is a viviparous anamniote that develops a yolk sac placenta composed of: a) uterine mucosa, b) egg envelope and c) fetal yolk sac mucosa. The transporting uterine mucosa is a squamous epithelial bilayer with prominent lateral and basal infoldings between contiguous cells. The surface cells have prominent secretion vesicles that empty their contents to the exterior. Immediately beneath the epithelium is a basal lamina and a profuse vascular supply with a continuous endothelium. The epithelium of paraplacental uterine sites is mucous. The tertiary egg envelope is retained throughout gestation and separates the distal part of the yolk sac from the maternal uterine mucosa. The egg envelope is compact on the yolk sac surface but displays delaminations on the uterine surface. The fetal yolk sac is composed of two portions, viz., a proximal, saccular region and a heavily vascularized, rugose, distal portion. The proximal portion has ultrastructural characteristics of a steroid hormone producing tissue, including massive smooth endoplasmic reticulum frequently forming whorled arrays. However, definitive evidence that the yolk sac is an endocrine organ is lacking. The distal portion of the fetal yolk sac is composed of a squamous epithelial bilayer that is separated from the underlying vascular network by a continuous basal lamina. The endothelium of the vessels is fenestrated. Cytoplasmic characteristics of these cells include an extensive Golgi complex, smooth walled caveolae, vesicles with electron-dense contents that are presumably endocytotic in nature and dense bodies that are suggested to be lysosomes that are involved in the digestion of material that may be yolk metabolites.

Subcellular alterations of cardiac fibers in rats subjected to hypothyroidism.

Subcellular changes of the atrial cardiomyocytes of rats submitted to hypothyroidism caused by administration of 1 mg/100 g of body weight of propylthiouracil showed a) swollen mitochondria and lysis of their cristae; b) myofibrils with marked heterogeneity of patterns, some exhibiting rupture and loss of continuity of their myofilaments; c) lesser concentration of atrial granules in the perinuclear area; d) abundant granular interstitial tissue and collagen separating the myofibrils.

Action of propranolol on the atrial cardiomyocytes of rats submitted to cold stress.

Subcellular changes of the atrial cardiomyocytes of rats caused by cold showed a) altered mitochondria with edema and lysis of crests; b) myofibrils with marked heterogeneity of patterns and ruptures, c) myofilaments disarrangement, partial necrosis and disintegration of filaments, d) lesser concentration of atrial granules in the perinuclear area. Atrial muscle fibers of propranolol-treated rats previously stressed by cold showed a marked decrease of the morphological alterations observed in the animals submitted to cold stress without propranolol protection.

Subcellular structure of the atrial myocardium of children in cases of atrial septal defect.

In order to study the initial development of myocardial ultrastructural changes owing to right atrium volume overload, myocytes have been studied in specimens taken from the right atrial wall and auricle of four children aged 1 to 6 years with ostium secundum atrial septal defect undergoing cardiac surgery. The younger patients (1 to 4-year-old children) we observed did not show diffuse and significant myocardial ultrastructural damages. The most significant myocardial changes were observed in the 2 older patients (six years old) as we found subcellular signs of myocardial hypertrophy such as an increased number of mitochondria, increased glycogen inclusions, areas of new sarcomerogenesis and nuclei lobulated and variably shaped. Focal degenerative changes, such as rupture of mitochondrial cristae and intercellular fibrosis were also noted. These changes may be considered as the initial features of myocardial hypertrophy because they were not as severe and diffuse as those usually seen in a marked functional failure.