[Interstitial linear keratitis (author's transl)]. There cases of interstitial linear keratitis are described. A linear infiltration was found in the anterior part of the corneal stroma, which remained stable throughout the observation period and became a dense scar. The disease shows frequent recurrencies, the etiology remains unknown. All three patients treated were of young age.


[Occlusion contact lenses (author's transl)]. A reliable inconspicuous occlusion therapy is achieved by fitting different, specially manufactured contact lenses. Based on a study of a number of cases, the author discusses the indications for a occlusion contact lens. These lenses provide a means for treating amblyopia in schoolchildren and adults, as well as for eliminating diplopia, photophobia and metamorphopsia.


[Acute glaucoma attack due to an operation on a serious carotis stenosis (author's transl)]. The subject of this report is an acute glaucoma attack, which occurred eight hours after an operation on a serious carotis stenosis following the increase in blood-pressure.


[Choroideremie in childhood (author's transl)]. By means of fluorescein angiography extensive defects in the pigmented epithelium found in choroideremia can be shown to be present in the first ten years of life. The degeneration of the vessels of the choroid and the functional damage to the retina do not seem to take place until later.


[Light microscope and scanning electron microscope findings in acute keratoconus (author's transl)]. An acute keratoconus was examined for the first time using a scanning electron microscope. The alterations in the epithelium of the cornea consisted of a reduction in microvilli and microplicae structures, disruption of the intercellular spaces with raised protrusions of epithelial cells in the region of the peak of the keratoconus or even of the complete disappearance of all regular surface structures. In the stroma distinct irregularities in the lamellae, sometimes even the formation of cavities in the region of the cornea peak, could be seen. These findings correlate well with the light microscope pictures and with the published transmission electron microscopic results.


[Refractometry after treating with atropine and cyclopentolat in childhood (author's transl)]. Using Rodenstock's Refraktometer refractometry was done on 314 hyperopic children (3--14 years) first after treating with Atropine and some weeks later after Cyclopentolat-hydrochlorid. 53,1% of them showed higher hyperopia after Atropine than after Cyclopentolat, the maximum in difference was 1,75 dptr. In another group of children with Cyclopentolat-treating the residual accommodation was determined by four different methods (Refactometer, Apparatus of Schober, Phoropter in a distance of 5,0 and 0,4 mtrs). The results show a minimum of accommodation 45 minutes after application of the drops under special conditions. These conditions are reported as well as a method of correction of hypermetropia due to the values of refractometry or residual accommodation.


[Fusion and aniseikonic problems in unilateral aphakia (author's transl)]. In 67 unilateral aphakic patients corrected with three different optic systems (conventional contact lens, spheric overcorrection and intraocular lens) aniseikonia and binocular vision are tested. Conventional contact lens leads to 7% aniseikonia and to fusion in only half of the cases. Patients with the two other systems show less than 3% aniseikonia and fusion in most cases. With each system only 10% of the patients reach normal stereoscopic vision. The poor results in unilateral aphakia corrected by conventional contact lens are pointed out.


[Multiple conjunctival malignant melanomas (author's transl)]. 5 1/2 years after excision of pigmented malignant melanoma which apparently arose in a nevus of the paralimbal bulbar conjunctiva, this 42-year-old male presented himself with a nonpigmented mass of the lid margin which also proved to be a malignant melanoma. "Acquired melanosis sine pigmento" was considered as a site of origin, but histopathologically there is more evidence that this melanoma arose in a non-pigmented compound nevus.


[Case report of a gonoblennorrhoea in both eyes (author's transl)]. It is reported of a serious form of a gonoblennorrhoea in both eyes of a five-week old girl. The baby had the typical symptoms of this disease. An intense local and general therapy with Penicillin G was applied and the infection ceased within two weeks after reception. The reason of the infection was a transfer from hand to eye, because her mother suffered from a gonorrhoeal urethritis.


[The Hruby-lens--used inverse (author's transl)]. The Hruby-lens may be used as a contact lens with the plano surface in contact with the cornea and the concavity facing the microscope. The observer surveys a large field of the fundus. By decentering the lens, adjacent and peripheral areas of the fundus are drawn into the observer's field. This increases further the total area of fundus that can be observed.


[Ophthalmological opinions for liability affairs. The question of smart-money (author's transl)]. Besides the compensation of the damage German Law includes also to compensate the noneconomical damage as pain, cosmetic or psychic damage etc. The ophthalmological expert is to state his opinion in accordance with individual consequences of the damage for the given person. He is not obliged to make proposition about the amount of financial compensation of smart-money because this point has to deal with other juridical circumstances of the specific conditions of every individual case.


[Primary hyperparathyroidism--bone turnover and osteitis fibrosa assessed by x-ray (author's transl)]. 1. In primary hyperparathyroidism an increased bone turnover is seen, accompanied by osteitis fibrosa (= fibroosteoclasia, FO) in severe forms of the disease. Both types of bone reaction may be detected by microradioscopy X-rays of the hand, extensive striation of metacarpal cortical bone indicating increased bone turnover and subperiosteal resorption of phalanges pointing to FO. 2. In the present study 65 patients with proven PHPT were evaluated before and 39 after operation. Microradioscopy was combined with biochemical assessment of hyperparathyroidism including alkaline serum phosphatase (aPh) as an index of osteoblastic activity, hydroxyprolin excretion (HyPro) reflecting bone turnover, immunoreactive parathyroid hormone levels (PTH), serum calcium (SCa), urinary calcium (UCa), serum inorganic phosphorus (SP) and clearance of phosphate (Cp). A comparison was made with the incidence of renal stone disease and the degrees of metacarpal striation (StG) and subperiosteal resorption (UG) were followed after operation. 3. Preoperative X-rays of 60% of the PHPT subjects showed increased StG and/or UG, and in 41,5% the diagnosis of PHPT was possible from the X-ray findings only. There existed a significant correlation between StG and UG on one hand and aPh, HyPro and PTH on the other. No correlation, either positive or negative, was seen between FO and the incidence of renal stones. After surgery, subperiosteal bone lesions disappeared in all patients, while intracortical striations persisted in half of the subjects despite the normalised bone turnover. Thus, primary hyperparathyroidism may not only lead to endosteal bone loss but to an irreversible intracortical bone deficit as well.


[Diagnostic procedures in diencephalo-hypophyseal insufficiency (author's transl)]. A functional diagnosis of the diencephalohypophyseal system was carried out in patients with Sheehan syndrome, chromophobic adenoma, craniopharyngioma, prolactin-producing pituitary tumours, acromegaly, hypothalamo-pituitary dwarfism and constitutional retardation. A combined insulin  hypoglycaemia/LH-RH/TSH test was performed to define frequency and extent of anterior pituitary insufficiency. With these illnesses, almost generally, a somatotropic insufficiency (except in acromegaly) was found. An impairment of gonadotropic function was often present, in general a pathologic LH-RH test correlating with a more or less developed androgen deficiency. An adrenocorticotropic insufficiency was found in most patients with sheehan syndrome, chromophobic adenoma and craniopharyngioma while in acromegaly and hypothalamo-pituitary dwarfism it was present less frequently, necessitating a substitution with corticoids. The TRH test reflects only incompletely a secondary hypothyroidism, and can be normal with organic processes of the diencephalo-hypophyseal region, making a T3 and T4 estimation in the blood decisive for a thyroid hormone substitution. A clear-cut separation of the hypothalamic from the pituitary cause of the insufficiency is neither possible with the LH-RH nor with the TRH test.


The distribution of HLA-Antigens in German patients with idiopathic hemochromatosis. HLA-phenotypes were determined in 31 (30 unrelated) patients with hemochromatosis and compared to the distribution of HLA-antigens in the general German population. A significant excess of HLA-A3 was observed (76.7% vs. 30.2%). The frequency of HLA-B7 was also increased (53.3% vs. 27.0%). However, the difference did not quite reach the level of statistical significance, when correction for multiple comparisons was made. Our findings are in accord with previous observations for different ethnic groups, indicating an association of IH with the A3/B7 haplotype.


[Reduced urinary prostaglandin E2-excretion and diminished responsiveness of plasma renin activity in patients with essential hypertension (author's transl)]. Under basal conditions prostaglandin (PG) E2-excretion was significantly lower in 35 patients with essential hypertension studied than in 22 age- and sex-matched controls (p less than 0.02). PGF 2 alpha--excretion was similar in both groups. Within the first 15 minutes after furosemide i.v., PGE2-excretion rose substantially less in the patients than in the controls (p less than 0.001), while the increase in PGF 2 alpha-excretion was not different for both groups. The coincident rise of plasma renin activity was significantly lower in the hypertensive (167% +/- 11, SEM) than in the normotensive (386% +/- 46) group (p less than 0.001). Our results support the assumption that a decrease in renal cortical (vascular?) synthesis of vasodilatating PG's may be the cause for both, the diminished secretion of renin and the increase of vascular resistance in the kidney, which are often associated in essential hypertension.


[Carcinoembryonic antigen (CEA) and CEA-like activities in ascites and pleura-effusions (author's transl)]. Carcinoembryonic antigen (CEA) was assayed in 18 samples of non-malignant and 21 samples of malignant effusions. In 95% of benign effusion CEA activity was found within normal limits and increased only in one case of Klebsiella pneumonia. In 57% of the 21 malignant effusions CEA levels were elevated and in 4 cases elevated titers were first indications of the malignancy of the effusion. In some cases remarkable differences between serum titer and effusion titer were found. Combined measurement of CEA activity in plasma and effusion increases diagnostic value.


Activity of procollagen-prolyl-hydroxylase and N-acetyl-beta-glucosaminidase in liver biopsies from patients with chronic liver diseases. In 5 mg of liver tissue obtained by needle biopsy from patients with chronic liver diseases, activity of both Procollagen-prolyl-hydroxylase and N-Acetyl-beta-glucosaminidase was measured. The activity of both enzymes increased due to the activity of fibrosis, but prolylhydroxylase increased more. The relation of these two enzyme activities in the development of liver fibrosis is discussed.


Dysfunction of the sympathetic nervous system in tetanus. A study of 3 cases. In severe cases of tetanus an overactivity of the sympathetic nervous system has been postulated because of the clinical symptoms including hypertension, fluctuating blood pressure, tachycardia, tachyarrhythmia and peripheral vasoconstriction. In the present study the involvement of the sympathetic nervous system in tetanus was investigated by serial determinations of plasma adrenaline (A) and noradrenaline (NA) in 2 patients who developed severe symptoms of tetanus and the characteristic cardiovascular disturbances. Sustained high circulating levels of NA and A could be observed indicating a prolonged overactivity of the sympathetic nervous system. In one case, the elevation of the NA level in plasma persisted until the disturbances of the motor nervous system ceased. In a third case of tetanus without cardiovascular abnormalities, the plasma NA and A only increased slightly on a few occasions. The results demonstrate that an overactivity of the sympathetic nervous system can complicate the course of severe tetanus.


Activation of human large bowel adenylate cyclase by methylated prostaglandin E2 analogues. The effects of methylated analogues of prostaglandin E2 upon the adenylate cyclase system in human colonic mucosa were tested. 16,16-dimethyl-prostaglandin E2 and 15-(S)-methyl-prostaglandin E2 increased the cyclase system in a dose-related manner. Maximal stimulation (about 250%) of enzyme activity occurred at a prostaglandin analogue concentration of 0.1 g/l. Diarrhea seen in patients treated with these orally effective prostaglandin analogues might in part be explained by activation of large bowel adenylate cyclase which is supposed to play a key role in the secretory process in this organ.


Enzyme-linked immunosorbent assay of allergen-specific IgG antibodies in bee sting allergic patients hyposensitized with pure bee venom. An ELISA is presented for detection of IgG antibodies to bee venom. By this method, sera of 11 bee sting allergic patients, who were treated with rapid hyposensitization with pure bee venom, were tested. The highest antibody titers were observed after 30 days of treatment, a maximum rise of 7.4 +/- 1.5 log 2-titer steps. Pure bee venom is shown to be more potent immunologically than whole body bee extract. Prediction of the clinical success, measured by tolerance to a bee sting challenge, is not yet possible using venom specific IgG determinations.


[Water-salt metabolism in members of the crew of Saliut-4]. The paper presents the results of studying the fluid-electrolyte metabolism in P. I. Klimuk and V. I. Sevastyanov before and after their 63-day flight aboard the orbital station Salyut-4. Postflight weight losses in P.I. Klimuk and V.I. Sevastyanov were 5.6 and 3.5%, respectively, the losses being attributed to body dehydration. Postflight both cosmonauts showed a trend for an increased renal excretion of potassium, magnesium, and calcium as compared with their food intake. Those were more expressed on the day after the water load application. Possible causes of the changes and the pattern of recovery of fluid-electrolyte metabolism after a prolonged space flight are discussed.


[Regulation of the vertical posture after flights on the Saliut-4 orbital station]. Stabilographic examinations of the crewmembers of the orbital station Salyut-4 demonstrated that one of the most characteristic manifestations of posture-tonic deconditioning induced by a prolonged exposure to weightlessness was an emergence of high-frequency oscillations (with a cycle of 0.1--0.15 sec) of the common center of body gravity, the fraction of the oscillations decreasing during the first weeks of the postflight period. After flight all the crewmembers showed signs of postural hypotension: an increase in the cardiac rhythm and a decrease in the pulse arterial pressure.


[Intensity of DNA synthesis in animal organs after a flight on the Kosmos-782 biosatellite]. With respect to H3-thymidine incorporation the rate of DNA synthesis in the liver, spleen and thymus of rats was determined in flight and synchronous rats. Six hours post-flight the rate of H3-thymidine incorporation into the liver of flight rats did not differ from the normal (vivarium controls) and was 50% higher than in the synchronous rats. In the spleen and thymus of flight animals this parameter was 60 and 33% below the norm. Similar but less pronounced changes in the spleen were found in the synchronous rats. Twenty-five days postflight the rate of DNA synthesis in lymph organs recovered completely and tended to increase, whereas in the liver it remained significantly below the norm.


[Human energy expenditures during a prolonged stay in a cyclically changing atmosphere]. The paper presents the results of studying man's gas exchange and energy expenditures as related to the composition of a cyclically changing environment of an altitude chamber. The experiments were carried out on a 24-hour basis. The paper gives the environmental parameters that physiologically were most adequate as the training factor. The respiratory reactions suggest that the enclosed environment used is suitable to prevent hypokinesia effects.


[Electrolyte makeup of the blood plasma and skeletal muscles of rats after a flight on the Kosmos-690 biosatellite]. Measurements of Na+, K+, Mg2+ and Ca2+ concentrations in the functionally different muscles (soleus, plantaris, diaphragm muscles) and plasma of the rats flown for 20.5 days aboard the biosatellite Cosmos-690 did not show any significant changes as compared with the controls. At the same time a decrease of the K+/Na+ ratio and a similar shift of Mg2+ and Ca2+ concentrations in plasma of irradiated rats as compared with these of non-irradiated animals demonstrated that the combined effects of space flight factors and gamma-irradiation influenced the system of ionic homeostasis in the blood. In the animals sacrificed on the R + 1 day the K+/Na+ ratio in the soleus muscle changed in favor of Na+ and in the plantaris muscle in favor of K+, and remained essentially unchanged in the diaphragm. The comparison of the flight experiments with the ground-based controls showed that ion changes in muscles occurred due to ionizing radiation rather than due to weightlessness.


[Characteristics of the effects of the midbrain reticular formation on the heart and respiration in exposure to centripetal accelerations]. Experiments were carried out on white rats and rabbits exposed to transverse accelerations of 6--10 g for 5 min. Before, during and after centrifugation the reticular formation of the midbrain underwent high-frequency electric stimulation. During centrifugation the inhibitory effects of the reticular formation on the cardiorespiratory rhythm decreased, whereas stimulatory effects either remained unchanged or increased.


[Ultrastructure of the lymph nodes of dogs under prolonged external gamma irradiation]. The purpose of the present investigation was electron microscopy study of lymph nodes of dogs exposed to chronic gamma-irradiation during 6 years (with a total dose of 125 rad/year). The exposure induced changes in the cell composition of the paracortical regions due to a decrease of the count of small lymphocytes and a predominant increase of young blast cells with an altered ultrastructure. Chronic gamma-irradiation led to an increase of the number of plasma cells and emergence of intermediate cell forms due to "plasmatization" of lymphocytes and reticular cells.


[Significance of the vibration component in the injurious action of impact acceleration]. Animal experiments demonstrated that damped oscillations of the support construction induced by impact accelerations enhanced their damaging effect on dogs. Within the frequency range tested--from 20 to 178 Hz--the threshold of lesions of the lungs, heart and liver decreased and reached 34% at a frequency of 85 Hz. The level of liver lesions was inversely proportional to the frequency of the support oscillations. Lesions of the lungs and the heart were more expressed at 85 Hz and decreased with an increase or a decrease of the oscillation frequency. At a frequency of 130--176 Hz the effect of the vibration component was not seen.


[Tasks in planning biological experiments]. The paper describes certain cases of using mathematical methods in the planning of biological experiments. The paper presents an algorithm of the distribution of the experimental data based on dynamic programming. The paper discusses an application of computer-aided calculations for the formation of homogeneous groups of experimental and control tests.


Effect of sequential bleeding on body weight gain in rats. Monthly withdrawal of a total of 1.25--2.0 ml of blood from young, mature, inbred Fischer 344 rats produced no noticeable effects on common hematologic parameters, but it did cause a decrease in the rate of body weight gain. The difference in body weight between rats bled and not bled was evident 3 weeks after the study began, and the difference persisted throughout the 23-week study.


[Effect of motion sickness on the absorption of B group vitamins and ascorbic acid in the small intestine of dogs]. On the dogs with a Thiry-Pavlov fistula (an isolated loop of the small intestine) the effect of 30-min acceleration on the absorption of thiamine-bromide, riboflavine, pyridoxine-hydrochloride and ascorbic acid as well as on the gastric juice secretion was studied. It was demonstrated that back-to-forth linear acceleration increased vitamin B1 absorption, decreased vitamins B2 and B6 and ascorbic acid absorption, and altered secretion of gastric juice.


Recovery rate of the cardiovascular system in rabbits following short-term halothane anesthesia. Mean arterial pressure, cardiac output and heart rate were determined in eight male New Zealand white rabbits while conscious and after being anesthetized with halothane plus nitrous oxide for 15 minutes. Delivery of the anesthetic agent was stopped and the measurement repeated at 15, 30, 60 and 210 minutes. In a separate experiment blood samples were obtained for plasma renin activity in six rabbits before anesthesia, after 15 minutes of halothane plus nitrous oxide administration, and again 210 minutes after cessation of the anesthesia. Later, this experiment was repeated with the same rabbits except that they were allowed to breathe room air instead of the anesthesia. The halothane anesthesia resulted in decreased mean arterial pressure and cardiac output, but these returned to the preanesthetic levels by 15 minutes after stopping the anesthesia. Heart rate increased during halothane administration, and although it tended to return toward control levels after cessation of the halothane, heart rate was still elevated 210 minutes later. Halothane plus nitrous oxide produced an increase in plasma renin activity, which then subsided to normal by 210 minutes following anesthesia; breathing room air did not result in increases in plasma renin activity. These studies revealed that although short-term anesthesia with halothane plus nitrous oxide resulted in cardiovascular changes in rabbits, after cessation of the anesthetic agent the cardiovascular system quickly returned to normal.


Cardiovascular function in anesthetized miniature swine. Miniature swine anesthetized with pentobarbital were studied with respect to their cardiovascular function under control conditions and in response to catecholamines, baroreceptor inhibition, bilateral vagotomy and vagal nerve stimulation. Measurements included aortic pressure, heart rate, intraventricular pressure and its maximum rate of rise during contraction, carotid blood flow and resistance, femoral blood flow and resistance, and renal blood flow and resistance. The cardiovascular actions of norepinephrine, epiniphrine and isoproterenol were similar to those in other mammals, and the adrenergic receptor mechanisms also were susceptible to blockade with phentolamine or propranolol. Inhibition of the carotid baroreceptors was accompanied by elevation of aortic pressure, reflex bradycardia and increased femoral and renal resistances. Bileteral vagotomy was followed by hypertension, tachycardia and increased renal resistance. Changes in femoral resistance to these procedures differed between the two strains of miniature swine studied. Stimulation of the peripheral end of either vagus nerve was accompanied by bradycardia without hypotension.


A natural outbreak of transmissible murine colonic hyperplasia in A/J mice. Transmissible murine colonic hyperplasia was diagnosed in 6-month-old A/J mice kept under standard laboratory conditions. Bacterial cultures revealed the presence of Citrobacter freundii (4280). Clinical signs included rough coats, feces adhering to the anus, slight dehydration and rectal prolapses. A nonclotting sanquinous intestinal fluid and gross colonic thickening were frequently seen at necropsy. Morbidity was approximately 50%; mortality approximately 25%. Tetracycline appeared to be effective in controlling the disease.


An unusual neoplasm of adipose tissue in a rat. The light microscopic features of a spontaneous neoplasm of adipose tissue from a rat were suggestive of a mixed liposarcoma with a myxoid matrix. However, ultrastructurally, the cell characteristics were those of a hibernoma. These characteristics included cells containing lipid droplets of variable size, numberous pleomorphic mitochondria and close apposition to blood vessels. Lipofuscin granules and subplasmalemmal condensations were not observed ultrastructurally.


Comparison of pyloric ligation and pyloric cuff techniques for collecting gastric secretion in the rat. A comparison was made between two methods for collecting gastric secretion in the rat. The two included a pyloric ligation technique and a snare-type pyloric cuff which was surgically implanted 2 weeks before the collection was initiated. It was hypothesized that the surgical trauma associated with pyloric ligation would inhibit gastric secretion and thus yield smaller gastric samples with this procedure as compared to the cuff technique. No differences in volume of gastric secretion or total acid output were observed between the two methods.


[Venous blood circulation in the crew of the Saliut-5 orbital station]. Studies of venous circulation were continued in the space crewmembers of the orbital station Salyut-5. New data which demonstrated again that weightlessness induced symptoms specifically assoicated with blood redistribution and pressure increase in the jugular veins were obtained. It is suggested to further the studies of venous circulation and regional hemodynamics aimed at determining the time and degree of human body adaptation to weightlessness.


Multiple biopsies of guinea pig mammary glands during pregnancy and lactation. Mammary gland biopsies were obtained from 39 guinea pigs during late pregnancy, lactation and weaning. Up to eight samples, each weighing 60--200 mg, were taken from each animal in two independent studies. No mortalities resulted, and no interference with lactation or suckling was observed.


Surgical exposure of the optic nerve in the guinea pig. A lateral orbitotomy approach was used to surgically expose the optic nerve in the guinea pig. This approach was excellent for experimental access to the optic nerve with minimal trauma to the eye.


A semiautomated procedure for rapid intrarectal instillation of fluids in the guinea pig. A penumatic operated semiautomatic system was developed for the intrarectal instillation of solutions in the guinea pig. The apparatus permitted one person to inject large numbers of animals at considerable savings in time compared to manually operated syringe techniques. The procedure was shown to be both rapid and safe for administering solutions intrarectally in the guinea pig.


Urolithiasis in ferrets (Mustela putorius). Urinary calculi was observed frequently in ferrets which were from a group used for influenza research. They were submitted for necropsy with various clinical signs. The calculi were composed of magnesium ammonium phosphate hexahydrate and were found in the pelvis of the kidney, urinary bladder and urethra. Crystals of undetermined nature occasionally were observed in the kidneys.


Determination of body surface area in neonatal swine. The body surface area of 30 neonatal pigs of both sexes, weighing 445--1,976 g, were determined by the direct skinning technique. The range of measured body surface area values was 635--1,400 cm2 (mean = 895.1 cm2). The regression line, fitted to a scatter diagram and calculated by the least square method, was found to be Y = 337.2 + 0.553X; where X was body weight expressed in grams and Y was body surface area expressed in square centimeters.


General anesthesia for newborn pigs.

General anesthesia for newborn pigs. A safe technique for the induction and maintenance of general anesthesia in newborn pigs was accomplished. After premedication with atropine sulphate, anesthesia was induced by giving a mixture of oxygen, nitrous oxide and 2.5% halothane introduced by face mask. An endotracheal tube was inserted, and anesthesia was maintained using 0.5--1% halothane. Recovery was prompt, and there were no postoperative complications related to anesthesia.


A simple, reliable and inexpensive method for the collection of rat urine. Aluminum foil attached to the bottom of hanging-type rat cages approximately 10 cm from the front of the cage was used for collecting rat urine. Most urine samples were obtained within 1 hour of placing the rat in the cage.


Rodent housing units for field studies.

Rodent housing units for field studies. Rodent housing and nesting units were constructed from acrylic and provided with concrete tops. These hexagonal units, placed in a wooded field, were inhabited by deer mice (Peromyscus maniculatus). The use of the field housing units provided an effective method for observing free-ranging wild rodents.


Accelerated serum sickness in the rabbit. IV. Characteristic endarteritis in the pulmonary artery. A unique angiitis developing in acute serum sickness in the rabbit was studied by immunofluorescence and light microscopy and by transmission and scanning electron microscopy. The angiitis occurred predominantly in the pulmonary artery and was characterized by a prominent accumulation of monocytes in the subendothelial space. During the early stage, scanning electron microscopy revealed the occurrence of various endothelial alterations, especially the formation of many endothelial holes leading to a subendothelial emigration of monocytes. There was neither emigration of polymorphs nor significant thrombotic lesion, and it is possible that this was due to a paucity in the amount of immune complexes deposited. The monocytes ingested platelets and fibrin, suggesting their preventive role in the development of thrombotic changes. The intimal change resolved within several days, leaving only slight fibrosis. A distinct resemblance in the disease process between this type of angiitis and acute serum sickness nephritis is emphasized.


Cell stroma interactions in aortic endothelial cell cultures. The behavior of bovine aortic endothelial cell cultures indicates that they interact with the extracellular materials they produce. In nonconfluent cultures the basal part of the cell is oriented on the plastic of the culture dish with the apex facing the culture medium. At confluence, fibrillar and ruthenium red-stained material, partly proteoglycan in nature, appears beneath the cells. In older cultures, a second layer of endothelial cells grows beneath the original one next to the plastic. This layer is oriented differently, being inverted in that the apex of the cells points to the plastic and the base toward secreted extracellular materials. Because of this orientation, cells tend to peel off the dish. The morphologic sequences thus suggest that polarity of endothelial cells in culture depends on its environment, with a hierarchy of polarity. In the absence of matrix materials, orientation is determined by the plastic. When extracellular materials form, endothelial cells then orient on them. Thus, the cells appear to manufacture and secrete the molecules on which their topography depends. Smooth muscle cells from the same bovine aortas do not seem to have this polarity. Glycosaminoglycans synthesized by the two cell types also differ.


Ultrastructural localization of complex carbohydrates in rat monocytes and peritoneal and alveolar macrophages. Complex carbohydrates are demonstrated in lysosomes and other organelles of rat monocytes and macrophages by means of ultrastructural morphochemical techniques for localizing acidic groups and vicinal glycols that are characteristic of glycoconjugates. The presence of glycoconjugates in various cell organelles differ in monocytes and macrophages from different sites. Bone marrow and blood monocytes contained glycoproteins with periodate-reactive vicinal glycols, as shown by the periodate-thiocarbohydrazide-silver proteinate sequence in lysosomes, a population of small vesicular structures, and Golgi lamellae. However, these cells contained no dialyzed iron or high iron diamine reactivity indicative of acidic groups. Alveolar macrophages were similarly periodate-thiocarbohydrazide-silver proteinate-reactive, and contained a variable degree of dialyzed iron and high iron diamine reactivity demonstrative of acid mucosubstances in lysosomes. Peritoneal macrophages, on the other hand, exhibited highly reactive lysosomes with all three techniques, and revealed a population of periodate-thiocarbohydrazide-silver proteinate-positive vesicles not previously recognized and not readily discernable by other means. These cells also displayed periodate-thiocarbohydrazide-silver proteinate staining in large cisternal elements, possibly related to Golgi-endoplasmic reticulum-lysosome (GERL) and in other Golgi complex-related elements, as well as in cisternae of rough endoplasmic reticulum.


Ultrastructural study of nephritis induced in Brown Norway rats by mercuric chloride. Chronic intoxication by mercuric chloride induces a two-phased nephropathy in Brown Norway rats characterized at first by a linear fixation of antiglomerular basement membrane antibody, then by a granular arteriolar and glomerular fixation of IgG superimposed on the linear one. On the 8th and 9th days, concomitant with the glomerular fixation of antiglomerular basement membrane antibodies, electron microscopy studies demonstrated an influx of monocytes into the glomerular and interstitial capillaries and a focal detachment of the glomerular endothelial cells. On the 14th and 15th days, subendothelial heterogeneous material and scattered subepithelial deposits appeared in glomeruli. By the 60th day, no cellular infiltration nor glomerular endothelial alterations persisted. Subepithelial glomerular deposits were seen in half of the animals, and abnormal deposits situated between muscular cells of the arteriolar walls were seen in all of them. These observations suggest that the glomerular fixation of antiglomerular basement membrane antibodies induces transient alterations of the inner aspect of the glomerular capillary wall. Arteriolar and subepithelial glomerular deposits confirm the idea that an immune-complex disease replaces the antiglomerular basement membrane antibody-mediated process. The morphologic expression of the transition between these two mechanisms is evident around the 15th day.


Characterization of lipid-laden aortic cells from cholesterol-fed rabbits. III. Intracellular localization of cholesterol and cholesteryl ester. The subcellular sites of accumulation of cholesterol and cholesteryl esters in rabbit atheromatous cells, were investigated by morphologic and biochemical techniques. Electron microscopy of lipid-filled cells in situ in atheromatous aortas of cholesterol-fed rabbits revealed lipid accumulation in the cytoplasm as lipid droplets and within lysosomes in the form of lipid globules, membranous whorls, and crystals. When such cells were isolated from the rabbit aortas by enzymic digestion, and then treated with Flickinger's aldehyde fixative containing 0.2 per cent digitonin, characteristic digitonide-lipid complexes ("spicules") were observed in discrete sites of the cytoplasm distinct from the cytoplasmic droplets. If these cells were first stained cytochemically for acid phosphatase and then treated with digitonin-aldehyde fixative, enzyme reaction product was found associated with the spicules indicating that the lysosomes of the atheromatous cells possess digitonin-reactive lipid. Subcellular fractionation of isolated rabbit aortic foam cells by sucrose density gradient centrifugation demonstrated the coequilibration of most of the intracellular unesterified cholesterol with low density lysosomes. Some cholesteryl ester was also associated with low density lysosomes, although most was found in a lipid droplet fraction of very low density. Together the results indicate that in rabbit atheromatous cells, lysosomes are the site of accumulation of intracellular cholesterol in excess of that structurally associated with membranes and that both cytoplasmic droplets and lysosomes are depot sites for cholesteryl esters.


The use of Reuber hepatoma cells for the study of a lipopolysaccharide-induced macrophage factor: glucocorticoid-antagonizing factor. Endotoxin-stimulated glucocorticoid-antagonizing factor (GAF) was assayed by its specific inhibition of hydrocortisone-induced synthesis of phosphoenolpyruvate carboxykinase. Defined induction of phosphoenolpyruvate carboxykinase synthesis in hydrocortisone-treated rat hepatoma cells permitted reliable quantitation of GAF and analysis of the mechanism of cortisol antagonism. GAF was present maximally in serum 2 hours after endotoxin challenge in mice; however, GAF production could be suppressed by pretreating mice with indomethacin or cortisol. Endotoxin-tolerant mice were also nonresponsive to endotoxin-stimulated GAF production. Gel filtration on Sephadex G-200 resolved four regions of glucocorticoid-antagonizing activity in serum from endotoxin-poisoned mice, two of which were not present in normal serum. Cortisol antagonism by GAF resembled that of insulin; however, insulin differed from GAF in its ability to antagonize dibutyryl cyclic AMP. Unlike insulin, endotoxin-induced serum glucocorticoid-antagonizing activity was heat-labile at 70 degrees C. GAF antagonism of hydrocortisone was partially reversible but did not act in a competitive manner. Production of hepatoma growth inhibitory activity and glucocorticoid-antagonizing activity in serum were closely associated, indicating a common methanism for their generation.


Morphology of the hemostatic plug in human skin wounds: transformation of the plug. The transformation of hemostatic plugs in human skin wounds was studied in vivo after bleeding had stopped. Standardized bleeding time incisions were made on the dorsal side of the forearm of four normal male volunteers. The wounds were excised by punch biopsy 10 minutes, 30 minutes, or 2 hours after they had been made and studied by light and electron microscopy. The wounds were filled with red blood cells, and a network of fibrin strands was found in the wound, particularly near transected vessels. Polymorphonuclear leukocytes were encountered within transected vessels and at 2 hours also in the wounds and in concentric rings around the vessels up to 0.5 mm. from the wound. On top of the wounds a superficial scab, consisting of red blood cells and presumably air-dried proteins, had formed. Hemostatic plugs were found at the ends of transected blood vessels. At 10 minutes the plugs consisted of largely degranulated platelets which showed strong interdigitation. Fibrin was still absent from the center of the plugs. At 30 minutes the platelets became less densely packed, and small fibrin fibers were deposited between the platelets in large peripheral areas of the plugs. At 2 hours some of the platelets had assumed rounded shapes with few interdigitations and larger spaces between them. Areas in the plug with platelets that had lost their integrity alternated with areas where platelets still had their cytoplasmic matrix and were interdigitated. Fibrin fibers were especially demonstrable between the degenerated platelet vesicles. This occurred everywhere in small hemostatic plugs and in the periphery of larger plugs. In one individual it was also observed in the center of large hemostatic plugs. In the other individuals fibrin was present centrally as amorphous dark staining material which was fibrillar in tangential sections.


Analysis of transmembrane dynamics of cholera toxin using photoreactive probes. Using sodium dodecyl sulfate--polyacrylamide gel electrophoresis and autoradiography, we have shown that 125I-labeled cholera toxin binds to Newcastle disease virus. Pretreatment of Newcastle disease virus with "cold" cholera toxin (at 37 degrees C for 30 minutes) inhibits the binding of 125I-labeled toxin in a subsequent incubation (at 37 degrees C for 30 minutes). These results suggest that cholera toxin binds to Newcastle disease virus in a specific manner. The precise receptor for toxin is unknown in Newcastle disease virus but it is presumed to be the ganglioside GM1. We have previously shown that the photoreactive probe 12-(4-azido-2-nitrophenoxy)stearoylglucosamine[1-14C] labels the membrane proteins of Newcastle disease virus. Since the reactive group of the probe, ie, N3, resides within the membrane bilayer, studies were initiated to determined which, if any, of the subunits of cholera toxin cross the membrane of Newcastle disease virus and become radioactively labeled upon photoactivation of the probe at 360 nm. After a 15-minute incubation of cholera toxin with Newcastle disease virus containing the photoreactive probe, irradiation effected the 14C-labeling of the active A1 subunit of cholera toxin. Irradiation of cholera toxin in solution with an equivalent amount of probe but without virus resulted in no labeling of toxin subunits.


Substructure of human erythrocyte spectrin. The human erythrocyte structural protein spectrin and its subunits I, II were isolated in the presence of Na-dodecyl-sulfate by gel filtration and preparative gel electrophoresis. After removal of the detergent, spectrin alpha-helical content is comparable to spectrin isolated without detergent. Subunits I and II formed single bands in isoelectric focusing (pI = 5.6) and in Ornstein-Davis disc gel electrophoresis systems, indicating the individual subunits are homogenous in nature. The molecular weights of the subunits I and II, determined by Ferguson plot, are 237,500 and 238,600, respectively, which is in good agreement with values obtained by the standard SDS gel relative mobility method. Limited tryptic digestion of spectrin and two-dimensional peptide maps of the individual subunits cleaved by S-cyanylation reaction showed dissimilar patterns, suggesting differences in primary structure between the two subunits.


Role of bound water in biological membrane structure: fluorescence and infrared studies. Bound water is a major component of biological membranes and is required for the structural stability of the lipid bilayer. It has also been postulated that it is involved in water transport, membrane fusion, and mobility of membrane proteins and lipids. We have measured the fluorescence emission of membrane-bound 1-anilino-8-naphthalenesulfonate (ANS) and the infrared spectra of membranes, both as a function of hydration. ANS fluorescence is sensitive to polarity and fluidity of the membrane-aqueous interface, while infrared absorption is sensitive to the hydrogen bonding and vibrational motion of water and membrane proteins and lipids. The fluorescence results provide evidence of increasing rigidity and/or decreasing polarity of the membrane-aqueous interface with removal of water. The membrane infrared spectra show prominent hydration-dependent changes in a number of bands with possible assignments to cholesterol (vinyl CH bend, OH stretch), protein (amide A, II, V), and bound water (OH stretch). Further characterization of the bound water should allow its incorporation into current models of membrane structure and give insight into the role of membrane hydration in cell surface function.


Malignant mesothelioma presenting in the pleura and peritoneum. Malignant mesothelioma presenting in the pleura and peritoneum is described in a middle-aged man. The patient lacked significant asbestos exposure which is not unexpected from both the clinical literature and animal inhalation tumor data. Computerized axial tomographic correlation is provided. Partial remission was achieved with the administration of adriamycin and DTIC.


Metastases from carcinoma of mammary gland: an autopsy study. Information on metastases from carcinoma of the mammary gland in an autopsy study of 707 cases occurring in white women over a 15-year period are presented and tabulated. Multiple primary cancers occurred in 19% of the cases. Of the 137 cases that exhibit more than one neoplastic malignancy, 31 (23%) were present in the contralateral mammary gland. Seventy patients had no metastasis from the mammary cancer at the time of death, and 55 of these patients had another cancer. Additional information has been added concerning the frequency of metastasis in parathyroid and thymus. When a parathyroid contains a metastasis, extensive metastases were noted in many organs and thus represents a late stage of the cancer.


Five-day continuous infusion of 5-fluorouracil for advanced colorectal, gastric, and pancreatic adenocarcinoma. In a retrospective study, 58 patients with advanced colorectal carcinoma received one or more 5-day infusions of 5-FU at 20 mg/kg per 24 hours followed by weekly IV 5-FU at 15 mg/kg. In 36 patients who received the infusion as first treatment (Group A), the response rate was 23% with a median duration of response of 8.0 months. No improvement in survival was noted. In 22 patients treated with the infusion after relapse on weekly 5-FU (Group B), the response rate was 10.5% with a median duration response of 4.5 months. Stable disease for 3-6 months was seen in 21%. Survival in Group B was improved when compared with a similar group of patients treated by weekly 5-FU without infusion (Group CB), but statistical significance was not obtained. Twenty percent of patients were alive two years after relapsing on weekly 5-FU when given the five-day infusion 5-FU and re-initiated on weekly 5-FU. Toxicity to the five-day infusion of 5-FU was minimal. Three of 69 (4.3%) infusions were not completed because of toxicity. A separate review of procarbazine indicated that it was minimally active in colorectal carcinoma. Other patients with gastric and pancreatic carcinoma were reviewed but no statistical significance for 5-FU infusion was seen for survival. A five day continuous infusion of 5-FU is recommended for colorectal cancer patients who relapse on weekly 5-FU therapy. Further study of the infusion in combination with other chemotherapy is warranted.


Increased incidence of breast carcinoma in patients with irradiation for post-partum mastitis: a screening situation. In Rochester, New York, 606 women were treated with ionizing radiation for post-partum mastitis, mostly between 1940 and 1955. Two-thirds of all breasts were treated, the average dose per breast being 377 rads (at 2.5 cm breast depth). Mammographic examinations were performed on 265 of these women still residing in this vicinity. Two nonpalpable carcinomas (with no axillary node metastases) were found in the twelve breast lesions that have been biopsied. Some of the biopsies revealed premalignant changes. It is recommended that women in this high-risk category have close medical supervision, as well as periodic mammographic evaluation, and that the importance of periodic breast self-examinations should be emphasized.


Reductive surgery of unresectable lung cancer: a case report. The only effective therapy for non-small-cell lung cancers has been surgical resection. In the present study a patient with unresectable adenocarcinoma of the lung was treated by chemoimmunotherapy and surgery, and has been doing well for 19 months following surgery. The case is presented as an example of treatment of advanced lung cancer by combined modality approach.


Fibroxanthosarcoma of the head and neck. Fibroxanthosarcoma is a variant of malignant fibrous histiocytoma probably derived from the primitive tissue histiocyte. It occurs rarely in the head and neck. This lesion may be confused with the benign atypical fibroxanthoma. However, newer histologic criteria may allow definitive differential diagnosis which is important because of the agressive biologic behavior of fibroxanthosarcoma. Aggressive initial surgery with a consideration of regional lymphadenopathy offers the best chance for cure.


Survival rates of breast carcinoma patients after surgery and anaesthetic. Eighty-nine breast cancer patients were studied for the end result of therapy. During surgery, the anaesthesia administered was either halothane (61 cases) or ether (28 cases) mixture with nitrogen and oxygen. The holstead method for mastectomy was used for all cases. The results showed that the type of anaesthesia influenced the end results of therapy of breast cancer patients. The survival rates of patients receiving halothane were much higher than those of ether anaesthetized cases. The differences were most pronounced among cases who received both preoperative radiotherapy and postoperative chemotherapy, and in cases with metastasis into regional lymph node. A comparison  of groups of patients on the basis of such parameters as the anaesthetic used, age and degree of tumor progression (according to TNM classification and post-operative histological assays) showed them to well matched. These results may be explained by the effects of the anaesthesia on the role of immunity in controlling tumor cell implantation and growth of metastasis.


Spontaneous retroperitoneal hemorrhage from a ruptured hypernephroma. The clinical presentation and roentgenographic findings of renal cell carcinoma have been consistently variable. These patients can appear with flank pain mimicking ureteral colic, flank tumors, or symptomatic metastasis [1]. Systemic cardiac manifestations including cardiomegaly with congestive heart failure due to arteriovenous fistula formation have been reported [2] Roentgenographic findings may show the tumor to be either vascular or avascular. It may present as a spontaneous perforation of the pelvic ureteral system which is demonstrated by intravenous pyelography (3). In this article, we describe a case of hypernephroma in a cyst wall causing severe spontaneous hemorrhage in the retroperitoneal space resulting in a state of hypovolemic shock.


Production and secretion of proteolytic enzymes by normal and neoplastic cells. A possible mechanism for tumor cell invasion of normal tissue might be secretion of proteolytic enzymes. This study compares and contrasts production and secretion of proteinases by cell cultures of normal and chemically transformed mouse epithelial cells. Lysates of normal and neoplastic cells contain similar amounts of neutral proteinase, cathepsin D and plasminogen activator. Neither collagenase nor elastase could be identified in lysates of, or serum-free culture medium bathing, normal or neoplastic cells. Neoplastic cells secrete ten times more plasminogen activator than normal cells. Our data support the hypothesis that plasminogen activator produced by neoplastic cells could fuction to activate latent proteolytic enzymes secreted by connective tissue cells which might result in spread of neoplastic cells into normal tissue.


Thoracic surgeons and their surgical practice. The work characteristics of thoracic surgeons were studied as part of a national study of surgeon manpower. Thoracic surgeons were found to have the greatest operative work loads, longest workweeks, and equivalent median incomes compared with all other surgical specialties. The major conclusion that the number of thoracic surgeons was adequate concurs with the findings of the National Thoracic Surgery Manpower Study on number of practitioners.


Survival with residual tumor on the bronchial margin after resection for bronchogenic carcinoma. Sixty-four (14.7 percent) of 434 consecutive patients having pulmonary resection for bronchogenic carcinoma were found to have microscopic residual tumor on the cut margins of the resected specimens. These subjects were further subdivided histologically into those with direct extension of the tumor (34 patients), lymphatic permeation (14 patients), clumps of cancer cells in parabronchial tissues (six patients), and the presence of carcinoma in situ change (10 patients). Bronchopleural fistulas developed in eight (12.5 percent) of 64 patients. The operative mortality rate was 15.6 percent, with four of the deaths occurring as the result of bronchopleural fistulas. Thirty-two patients (50 percent) survived 1 year, 21 (32.8 percent) survived 3 years, and 15 (23.4 percent) lived for 5 years or more. The patients with tumor in the submucosal and peribronchial lymphatics had the worst prognosis. 78.6 percent having died within 1 year and the remainder within 3 years. All 5-year survivors were men with squamous cell carcinoma and had relatively small tumors (mean diameter 2.9 cm). No direct relationship between the length of the resected bronchial stump and survival could be established; a short stump did not preclude long survival. The possible factors involved in the relatively high 5 year survival rate in this group of patients and the therapeutic implications of these factors are discussed.


Esophageal-atrial perforation due to recurrent esophagitis 18 years after esophageal bypass surgery. A 62-year-old man presented with a grand mal seizure, progressive abdominal distention, and refractory hypotension 18 years after colonic bypass of a benign stricture of the low middle third of the esophagus. He died 3 hours after admission to the hospital. The patient had a history of liniment ingestion in childhood plus a long history of dysphagia and substernal pain. Autopsy disclosed a large ulcer of the anterior wall of the distal esophagus, which had eroded through the posterior wall of the left atrium. Histologic examination revealed chronic esophagitis with fibrous obliteration of the esophageal wall, pericardium, and left atrial myocardium near the site of perforation. Foreign material was present within small arteries of multiple viscera, and in several of these fragments transverse striations were demonstrated. Esophageal-atrial perforation is a rare but fatal complication of chronic esophageal ulceration. The clinical and pathological features of this and previously reported cases of nontraumatic esophageal-atrial perforation are reviewed.


Specific afterload reduction with parenteral hydralazine following cardiac surgery. In a group of seven patients who had had cardiac operations, intravenous (IV) hydralazine was used to provide afterload reduction in situations of severe left ventricular dysfunction. Despite fluid loading, inotropic support with dopamine, and afterload reduction with sodium nitroprusside, the patients had persistent states of low cardiac output and high systemic vascular resistance. Administration of sodium nitroprusside was limited by its effect on preload and blood pressure, so that it necessitated frequent fluid challenges. The addition of IV hydralazine to this regimen caused a mean increase of 44.7% in the stroke index and a mean reduction of 28.6% in systemic vascular resistance without significant change in pulmonary artery wedge pressure, mean arterial pressure, or heart rate. Rapid weaning of sodium nitroprusside and, on occasion, dopamine was facilitated. Frequent fluid challenges to restore preload were unnecessary. Dose requirements of hydralazine were small: 2.5 to 5.0 mg IV initially, and then a maintenance dose of 2.5 to 7.5 mg IV every 4 to 6 hours. These preliminary clinical observations indicate that in patients with low cardiac output--high resistance states and normal or elevated preload, the important benefit of specific afterload reduction may be provided by parenteral hydrolazine in the early period following cardiac surgery. Prospective, controlled studies with this agent in this situation appear warranted.


Hepatitis risk in cardiac surgery patients receiving factor IX concentrates. Experience with the clinical use and hepatitis risks of factor IX concentrate (Proplex) in cardiac surgical patients is presented in this report. Seventy-five patients received the concentrate for severe intraoperative or postoperative hemorrhage and 75 patients constituted matched controls. The incidence of probable type B viral hepatitis in patients receiving factor IX concentrate was 13.8 percent (four of 29) versus zero percent (zero of 29) in control patients (difference not significant). However, there was a greater incidence (p less than 0.05) of anti-HBs in patients receiving factor IX concentrate as compared to control subjects. No hepatitis-associated deaths or major morbidity were noted in these patients. It is confirmed that factor IX concentrate carries an associated significant risk of hepatitis. However, its use is justified in certain severe, acquired coagulopathies in which conventional platelet and fresh-frozen plasma therapy is inadequate.


Myocardial respiration and edema following hypothermic cardioplegia and anoxic arrest. The effects of 1 and 2 hours of hypothermic anoxic arrest and cardioplegia induced by Mg-lidocaine, K-Mg, or K on left ventricular mitochondrial respiratory function, blood flow, and edema were studied in 41 mongrel dogs. Mitochondrial respiration was assessed by the indices of oxidative phosphorylation. Myocardial temperature recorded in ventricular septum was kept at 20 degrees C during ischemic arrest and 10 minutes of reperfusion. Cardioplegic solutions did not influence noncoronary blood flow during cross-clamping of the aorta. Mitochondrial respiratory function remained at control levels after 1 hour of ischemia induced by hypothermic anoxic arrest or by Mg-lidocaine or K-Mg hypothermic cardioplegia. Mitochondrial state 3 respiration after 2 hours of anoxic arrest was significantly higher in Mg-lidocaine cardioplegia than in anoxic arrest (p less than 0.05), but myocardial edema was equivalent in both groups. Mg in the cardioplegic solution suppressed mitochondrial nonphosphorylating oxygen consumption. These data suggest that mitochondrial function after 1 hour of ischemic arrest at 20 degrees C and 10 minutes of reperfusion is not significantly depressed, but at 2 hours of ischemic arrest, mitochondrial respiration is significantly impaired. However, hypothermic Mg-lidocaine cardioplegia appears to be more effective in sustaining myocardial respiration than does simple hypothermic anoxic arrest when the anoxic period is extended to 2 hours.


Iatrogenic myocardial edema with potassium cardioplegia. Postischemic myocardial edema depresses left ventricular function and coronary perfusion. Pharmacologic cardioplegia is being used increasingly to enhance myocardial protection during cardiac operations. In the present study we varied the colloid osmotic and osmotic pressures and the infusion pressures of four cardioplegic solutions to determine their respective roles in producing or preventing myocardial edema in a nonischemic setting. We found that myocardial edema during potassium cardioplegia (1) is independent of infusion pressures, (2) is caused by isosmotic crystalloid solutions, (3) is worsened by hyposmolar crystalloid solutions, (4) is avoided by the addition of colloid, and (5) is avoided if the solution is made hyperosmotic with the addition of mannitol.


Surgical treatment for hypoplastic left heart syndrome: case reports. A 58-day-old girl with hypoplastic left heart syndrome underwent bypass grafting from the pulmonary artery to the descending aorta, ligation of the ductus arteriosus, and banding of the main pulmonary artery distal to the graft. Anastomoses of the graft were performed by partial clamping of the arteries under moderate surface hypothermia. The patient tolerated the procedure well and was discharged from the intensive care unit on the eleventh postoperative day, but she died on the twentieth day of metabolic derangement. Our total experience with this anomaly includes three other infants, and a summary of these patients and applied surgical procedures are presented. Surgical and diagnostic considerations for this anomaly based on our experiences are discussed.


Valve replacement for Ebstein's anomaly of the tricuspid valve. The role of valve replacement in the treatment of Ebstein's anomaly of the tricuspid valve remains controversial. Between 1965 and 1977, five patients with Ebstein's anomaly ranging in age from 11 to 57 years (mean 29) underwent tricuspid valve replacement in our institution. All of the patients were cyanotic but one, three were in Functional Class III, and two were in Class IV (New York Heart Association classification). The valve was placed above the coronary sinus. Plication of the atrialized portion of right ventricle was required in only one patient. Four patients had additional closure of an atrial septal defect. There were no deaths. On follow-up (range 1 to 13 years), four patients are in Functional Class I and one is in Class II. None is cyanotic. Four patients are in sinus rhythm and one has a pacemaker because of postoperative complete heart block. We conclude that valve replacement and, when necessary, plication of the atrialized right ventricle produce excellent clinical improvement.


Effects of phenylephrine on transmural distribution of myocardial blood flow in regions supplied by normal and collateral arteries during cardiopulmonary bypass. Cardiopulmonary bypass is frequently accompanied by decreased peripheral vascular resistance with resultant hypotension that is unresponsive to increased flow rates. Alpha adrenergic agonists are routinely used to increase peripheral vascular resistance and augment blood pressure. In this study, the effects of the alpha adrenergic stimulant phenylephrine on blood flow distribution during cardiopulmonary bypass in myocardium supplied by normal and collateral arteries were studied in eight mongrel dogs. Microsphere determinations of blood flow were made following augmentation of perfusion pressure with phenylephrine and were compared with intraoperative normotensive and hypotensive control levels. With systemic flow rates held constant, phenylephrine was infused in doses adequate to raise perfusion pressure to normotensive levels following hypotension. In the normal region (NR), blood flow was returned to normotensive control levels with flow favoring the subendocardium. In the region supplied by collateral vessels (CR), however, phenylephrine infusion failed to return flow to the normotensive control level in the subendocardial layer, and the flow imbalance present during hypotension was not corrected. An analogue model of the calculable resistances in the CR is presented, which indicates that phenylephrine increased resistance in the collateral vessels. Associated with this inflow restriction is decreased resistance or vasodilatation of the intramyocardial vessels supplied by collateral coronary arteries.


Efficacy of nitroprusside therapy in postcardiotomy low-output syndrome necessitating intra-aortic balloon counterpulsation. Serial hemodynamic measurements were obtained before, during, and after nitroprusside therapy over a 24 hour period in 19 patients requiring intra-aortic balloon pumping (IABP) for successful weaning from cardiopulmonary bypass. Nitroprusside, administered in doses ranging from 0.5 to 5 micrograms/kg/min, effected significant reductions in mean aortic pressure and systemic vascular resistance within 20 to 30 minutes. Mean aortic pressure decreased from 108 +/- 22 mm Hg to 85 +/- 27 mm Hg (p less than 0.005). Systemic vascular resistance decreased from 2,705 +/- 1,072 to 1,942 +/- 823 dynes sec cm-5 (p less than 0.005). 2n response to nitroprusside-induced decreases in left venticular afterload, cardiac indes increased from 1.83 +/- 0.58 to 2.04 +/- 0.54 L/min/m2 (p less than 0.025). Pulmonary capillary wedge pressure (PCW), right atrial pressure, right and left ventricular minute work indices, and the rate-pressure products did not change, indicating that nitroprusside administration during IABP further increased cardiac output without increasing ventricular filling pressure, ventricular work, or indices of myocardial oxygen consumption. The data suggest that nitroprusside, in conjunction with volume loading to optimal preload levels (PCW = 15 to 18 mm Hg), augments ventricular performance in postcardiotomy low-output syndrome by lowering impedance to left ventricular ejection through a direct dilator effect on vascular smooth muscle, without a direct effect on cardiac muscle. Thus it is a valuable pharmacologic adjunct during mechanical (IABP) support of the failing circulation.


Surgical correction of severe mitral prolapse without mitral insufficiency but with pronounced cardiac arrhythmias. Despite what was considered adequate pharmacological treatment, the condition of six patients with severe mitral valve prolapse but with trivial or no mitral regurgitation deteriorated. These patients had marked weakness, chest pain, dyspnea, and arrhythmias. Because these patients found their condition to be intolerable, the prolapsed mitral valve was repaired. Electrocardiography, treadmill stress testing, and left ventirculography performed following operation showed complete repair of the valve and significant improvement over the preoperative findings in all six patients. Repair of the floppy mitral valve did not eradicate all abnormalities; however, it did significantly improve the chest pain, weakness, dyspnea, and arrhythmias in all six patients. Five patients no longer require any medication. The prolapsed mitral valve contributed significantly to the symptoms and arrhythmias, but it could not have been the sole cause for these patients' signs and symptoms. With complete correction of the prolapse in all six patients, few of the signs and symptoms of the disease persisted. Repair of severe mitral valve prolapse without mitral regurgitation is recommended only for those patients who continue to be severely symptomatic from chest pain, dyspnea, or ventricular arrhythmias after an extensive trial of adequate medical therapy.


St. Jude Medical cardiac valve prosthesis: in vitro studies. The St. Jude Medical cardiac valve prosthesis is an all-pyrolitic carbon, bileaflet, low profile, central flow device. Prior to clinical use on intensive program of in vitro and in vivo testing was undertaken. Simulated radiographic studies determined that the tungsten impregnation needed to make the valve leaflets radiopaque was 0.013 inch. Steady-state flow and pulse duplicator studies demonstrated a high ratio of flow orifice to tissue anulus diameter with low transvalvular pressure gradients. Regurgitation was found to be acceptable. Flow visualization revealed central flow through all three flow orifices with minimal turbulence and vorticeal current formation. In vitro comparison with other available cardiac valve devices of various sizes demonstrated superior hemodynamic performance of the St. Jude Medical cardiac valve.


The porous-surfaced electrode: a new concept in pacemaker lead design. Three major problems which may be encountered with endocardial pacemaker electrodes are a lack of stable position, a chronic increase in stimulation threshold, and a diminishing magnitude of the sensed endocardial signal. These problems are particularly manifest in the atrium. Having previously shown that porous metal surfaces can support stable tissue ingrowth in both bloodstream and soft tissue environments, we set out todetermine the performance of porous-surfaced endocardial pacing electrodes in the atrial position. In two groups of six dogs each, J-shaped atrial leads with Elgiloy electrode tips (2.3 mm. in diameter, 2.3 mm. in length), having either conventional smooth surfaces (control) or porous surfaces (20 to 50 micron particle size) produced by powder metallurgy techniques, were positioned in the right atrial a-pendage. Stimulation thresholds and P-wave amplitude were repeatedly measured until the dogs were put to death 30 w-eks following implantation. The presence or absence of electrode fixation was observed and the atrial tissue reaction was examined grossly and by both light and scanning electron microscopy (SEM). The porous-surfaced electrodes demonstrated superior long-term stimulation thresholds which, at 30 weeks, averaged less then one third of those in the control group. In addition, the porous group showed a small but significant improvement in the amplitude of the sensed P wave. None of the smooth-surfaced electrodes showed fixation, and the tissue reaction consisted of a thick layer of granulation and fibrous tissue on the underlying endocardium, widely separating the electrode from the myocardium. In contrast, all of the porous-surfaced electrodes were fexed to the endocardium by fibrous tissue ingrowth into the surface pores. This tissue fixation of the electrode tip in close proximity to underlying myocytes explains their superior performance.


Long-term atrial pacing for sinus node disease with output-terminal programmagle pacemakers. Long-term transvenous atrial pacing for symptomatic sinus node disease, in the absence of atrioventricular conduction disease, confers the advantages of increased cardiac performance and probable freedom from systemic thromboembolism. Conventional ventricular pacing has been preferred, however, because of the complications of atrial pacing, mainly those of electrical and mechanical instability of currently available atrial electrodes. These complications have been circumvented with a new pacemaker, programmable for output terminal. This has allowed the institution of atrial pacing in seven patients, with its attendant advantages and the ability to reprogram noninvasively to ventricular pacing should atrial pacing fail. Such reprogramming has been accomplished without difficulty in one patient who developed second-degree atrioventricular block and one with electrode microdisplacement.


[Incidence of painful menstruation in Macedonia]. A total of 6930 pupils born between 1955 and 1966 were inquired by a questionnaire. It has been found that painful menstruation was present in 2786 pupils (40.20%) Along with a high percentage of painful menstruations, a high percentage of menstrual disturbances was recorded in younger pupils. Certain differences were found among the nationalities and also in relation to pupils from towns and villages.


[Morphologic analysis of a case of Sheehan's postpartal hypophyseal necrosis]. The post-mortem finding of a 39-year-old woman with the Sheehan postpartal necrosis of the hypophysis is described. This was the only such case of 16,580 obductions of women in the period from 1961 to 1976. The cause of death was cerebral encephalomalacia and non-specific bronchopneumonia. The death occurred five years after the last delivery and almost three years after the established clinical diagnosis.


[Tuberculous endometritis in the post-menopause]. During a period of 15 years, 71 cases of genital tuberculosis were diagnosed. Out of the two had postmenopausal tuberculous endometritis and were hospitalized for postmenopausal bleeding. The diagnosis was confirmed by the histological examination of the tissue obtained from the uterus.


[Acute myocardial infarct and pregnancy. A case report]. The authors describe a case of acute myocardial infarction in a healthy parturient in the 10th I. m. who had a spontaneous delivery without any major complications. Except for a strong stenocardial pain and unequivocal ECG findings, there were no other clinical or laboratory findings characteristic of acute myocardial infarction. The authors consider that a healthy heart in pregnancy is probably protected from myocardial infarction by some known and unknown factors. They claim, however, that myocardial infarction can occur and that it is possible to detect it if adequate attention is paid to stenocarial pain in pregnancy.


[Our 1st experience with paracervical analgesia in cerclage of the cervix]. Cerclage cervicis in paracervical analgesia with lidocaine and diazepam premedication has proved a very simple procedure. It can successfully be applied in pregnancy, without any harm to mother or fetoplacental unit. Out of a total of 50 cerclage cervicis in 48 women (96%) completed their pregnancy successfully. Earlier these women had had 94 pregnancies but with a successful issue only in 31 cases (32.97%). These results, supported by data on the decreased perinatal mortality from 232.5% to 40%, also fully justify the use of paracervical analgesia by lidocaine.


[Qualitative diagnosis of pregnancy using the immunologic Gonavislide test]. Gonavislide is the latex agglutination "slide" test in which, on the basis of a new reaction principle, a direct reaction between HCG and anti-HCG occurs. The test was applied in 300 pregnant and 200 non-pregnant patients. The accuracy of the test in either group was 100% after correction.


[Hysterosalpingography in sterility].

[Hysterosalpingography in sterility]. From 1967 to 1975 the authors performed 500 hysterosalpingographies in 851 women examined for sterility. Hysterosalpingography was carried out under the diascopic control of an electronic amplifier and a tele-monitor. As a contrast medium only the water-soluble Joduron U-S (Cilag) was used. In 286 women (57%) primary sterility and 214 (43%) secondary sterility were established. Radiographic analysis revealed 209 anomalies of the uterus, 114 of which related to hypoplastic uterus. In 286 women with primary sterility there was occlusion of one or both tubes in 62 cases (21.67%) and the sactosalpinx of one or both tubes in 48 cases (16.78%). In 214 women with secondary sterility, there was occlusion of one or both tubes in 66 cases (31.30%) and the sactosalpinx of one or both tubes in 48 cases (22.42%). In 500 hysterosalpingographies the intravasation of the contrast medium into the venous system occurred in 23 cases (4.60%) but there was not a single case of unatoward side-effects. Sixty-six women became gravid 1--6 months after hysterosalpingography, without the use any other kind of therapy.


Statistical methods in cancer research.

Statistical methods in cancer research. This chapter has presented and elaborated upon some of the more fundamental statistical methods that can be applied to medical data and that appear most frequently in the present literature. Familiarity with these concepts is necessary for understanding information so analyzed and is the foundation for critical evaluation of a variety of medical data.


Cancer of the breast. Screening.

Cancer of the breast. Screening. Screening is a more complicated issue than has been indicated in this chapter. Long-term followup is essential to exclude misleading initial impressions, and survival predictions must stand this test. The problem of interval cancers must be acknowledged, and methods of developing more cost-effective systems that might provide even broader coverage of the population at risk have to be considered. Suffice it to say that mass screening for breast cancer can be accomplished. Large numbers of American women are sufficiently concerned about this disease to participate, as evidenced by the success of the National Cancer Institute/American Cancer Society Breast Cancer Detection Demonstration Projects. It has been demonstrated that breast cancers so small that they would previously be considered a pathological curiosity are detected with surprising frequency. The ultimate effect on survival time by this screening can of course only be determined after passage of time, but there is every reason to believe that it represents one of the really great advances in detection-diagnosis in recent history. The chief detection modality is mammography, and it is to be expected that technological advances in this area will permit images of even greater reliability and resolution at a level of radiation exposure that will be acceptable to everyone. The definitive role of thermography in detection of breast disease has yet to be fully determined. The maximal scientific benefit and the true impact of the screening demonstration projects will be realized only after long-term followup of the 280,000 participants.


Total joint arthroplasty. Introduction to the upper extremity. Total joint replacement in the upper extremity has developed in step with that of the lower extremity. The indications for treatment, the place of total joint arthroplasty in contrast to other forms of arthroplasty, and the criteria for patient selection have recently been classified. A number of problem areas are under biomechanical and clinical study, and most investigators are proceeding cautiously. In properly selected patients, however, prosthetic replacement offers great improvement in both relief of pain and joint function, and improvement should continue. The patient and physician should recognize the limitations that are inherent in any "artificial joint" replacement. Realistic  expectations would be for improvement that approaches, but rarely achieves, normal function.


Total joint arthroplasty. The shoulder.

Total joint arthroplasty. The shoulder. The experience with total shoulder replacement has led to a greater understanding of the large spectrum of pathology which is associated with glenohumeral cartilage loss. For the majority of patients, a simple "resurfacing" prosthesis with muscle repair is the best choice. With this type of implant, pain relief is consistent (92% in 50 shoulders), mechanical failures are rare (2%), and, with repair of all muscles, an opportunity is provided for maximal return of function.


Total joint arthroplasty. The elbow.

Total joint arthroplasty. The elbow. The first total elbow arthroplasty at the Mayo Clinic was performed in 1972, and it provided markedly superior results compared with previously performed procedures for elbow arthritis. However, a high revision rate (14%), due mainly to loosening (75%), tempered early enthusiasm for the procedure. Prospects for improved design and surgical technique based on our clinical experience and biomechanical data are encouraging. For the present, however, more limited procedures are recommended, and the total elbow arthroplasty is reserved for only a relatively few patients for whom there are no other viable surgical options.


Total joint arthroplasty. The wrist.

Total joint arthroplasty. The wrist. Total wrist arthroplasty, which has been performed in 101 patients, has proved to be a satisfactory procedure for the relief of pain and provision of mobility in the deformed wrist involved with rheumatoid arthritis. This procedure should not be performed after traumatic conditions in patients who expect to make heavy use of the wrist. Early cases were associated with technical problems in the development of the concept, but at present the procedure is reliable and is most often preferred to arthrodesis inpatients with rheumatoid arthritis.


Total joint arthroplasty. The hand.

Total joint arthroplasty. The hand. Joint replacement in the hand has developed on the basis of improved understanding of the pathophysiologic and the biomechanical factors involved in normal and diseased joints. Compromises are required in prosthetic design and surgical reconstruction, but function and appearance in deformed hands are susceptible to surgical improvement.


Series on pharmacology in practice. 2. Antiarrhythmic drug therapy. The selection of appropriate antiarrhythmic drug therapy depends on a knowledge of the drugs available, their spectrum of action, their pharmacokinetics, and their major side effects. It is important to know how the pharmacokinetics of a drug vary with different disease states so that appropriate adjustments to dosage can be made. Drugs with similar actions can be assigned into groups, and five different groups can be identified. The commonly used antiarrhythmic drugs are reviewed, and some of the newer drugs are discussed.


Usher's syndrome with unusual otologic manifestations. Usher's syndrome is characterized by a congenital hearing loss and retinitis pigmentosa. Ocular symptoms and signs are usually established at adolescence, and the hearing loss, the onset of which is at a young age, generally remains stable. The following case is of interest, therefore, because the hearing loss that had been present since birth progressed suddenly to total bilateral deafness in adulthood. There were no ocular symptoms at any time; the classic findings of retinitis pigmentosa were disclosed only on routine examination of the eyes.


Use of computed tomography in diagnosis of soft-tissue tumors. Soft-tissue tumors can evade the usual diagnostic methods. In the case presented, computed tomography proved to be the best diagnostic tool in demonstrating a malignant extranodal lymphoma. Computed tomography is useful not only in detecting a tumor but also in determining its extent. This aids the surgeon in selecting and conducting the most appropriate operation.