[Clinical experience with CS-1170 in children (author's transl)].

CS-1170 was tried in children with various infections, and the following results were obtained. Some studies on the drug's pharmacokinetics were also made, and the results were as shown below: 1. The time course of serum concentration following one-shot intravenous injections of 30 mg/kg in 8 patients aged between 3 and 13 was studied. The results were: 53.4 microgram/ml, 23.4 microgram/ml, 6.6 microgram/ml, 1.8 microgram/ml and 0.5 microgram/ml at 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours after the drug administration, respectively. Urinary recovery rate was 36% to 69.8% by 2 hours after, 10.9% to 70% by 2 to 4 hours after, 0.6% to 5.4% by 4 to 6 hours after the administration, and by 8 hours after the injection 91.3% of the drug was excreted in the urine. 2. Of 13 cases including 8 cases of bronchopneumonia, 2 cases of urinary tract infections, a case each of suppuration in the neck, lymphadenitis and pyothorax, CS-1170 was found to be effective in 10 cases (83.3%), while effectiveness of the drug was undeterminable in one case. 3. No remarkable side effect including allergic symptom such as eruption was observed, though transient elevation of GOT and GPT was noted in one case.


[Pharmacokinetics and results of clinical administration of CS-1170. II. Results of clinical administration of CS-1170 (author's transl)].

The intravenous preparation of CS-1170 was administered in 9 cases of pediatric disease and was excellent or good in 5 cases (55.6%). It was poor in 3 of 4 cases of Mycoplasma pneumonia. We think that the dose of 50 mg/kg/day can exert an effect regardless of the intensity of symptoms. Through our present experiences with the excellent or good cases, an intravenous drip or intratracheal injection for 3 approximately 5 days is effective. Although there was no abnormality in the biochemistry or electrolyte findings before or after administration, eruption developed in one of the cases in which the drug was administered for 6 days.


[Toxicological studies on fosfomycin-Na salt. I. Acute toxicity in mice and rats (author's transl)].

The acute toxicity of sodium fosfomycin (FOM-Na), a new antibiotic in ICR mice and Wistar rats has been investigated. The LD50 values in mice were: 1,230 (male), 1,225 (female) mg/kg by i.v.; 2,175 (m), 2,467 (f) mg/kg by i.p.; 2,625 (m), 2,662 (f) mg/kg by i.m.; 5,100 (m), 6,150 (f) mg/kg by s.c. and 8,020 (m), 7,300 (f) mg/kg by p.o. The LD50 values in rats were: 1,650 (m), 1,560 (f) mg/kg by i.v.; 2,060 (m), 2,000 (f) mg/kg by i.p.; 2,630 (m), 2,460 (f) mg/kg by i.m.; 5,100 (m), 4,320 (f) mg/kg by s.c. and 4,700 (m), 4,550 (f) mg/kg by p.o. Animals dosed only i.v. died within 2 minutes. Signs of toxicity in mice or rats given FOM-Na were similar and included motor activity depression, reduced respiration and occasionally tremors. Surviving mice or rats given FOM-Na developed no pathological changes of the drug specificity.


[Toxicological studies on fosfomycin-Na salt. II. Subacute toxicity in rats and rabbits (author's transl)].

FOM-Na solution in distilled water for injection, J.P., with its pH adjusted to 7.0 +/- 0.2 with diluted hydrochloric acid, was administered to rats and rabbits for subacute toxicity test. The results revealed the following: 1. It was intraperitoneally administered to Wistar rats each weighing 100 +/- 10 g at their age of 5 weeks, and intravenously into auricular veins of male albino rabbits each weighing about 3 kg, for 35 successive days except Sundays through one administration per day. There was no death in rats of both sexes with the doses less than 1,000 mg/kg, while 3/10 males and 5/10 females died with the dose of 2,000 mg/kg. In terms of general conditions, both stretched physical position and vocalization were noted, which were presumed to be attributable to the stimuli of the administration. In the postmortem examination mutual adhesion of organs in the peritoneum was noted, while in the lightmicroscopic examinations histological proliferation and adhesion were found out in the hepatic capsules or serous membrane of the intestine etc., but no abnormalities were detected in the other organs. In the mean body weights, there were no significant differences between the control group and the groups of males with doses less than 500 mg/kg and females with doses less than 1,000 mg/kg whereas in the groups of males with doses more than 1,000 mg/kg and the females with a dose of 2,000 mg/kg, a trend of reduced weight gain was noted in comparison with the control group. The feed intake also was reduced as the dose was elevated. In terms of the male group hematology, the In. P increased with doses higher than 250 mg/kg, while BUN was reduced in the groups with a dose of 250 mg/kg and doses higher than 1,000 mg/kg, and Na was reduced in the groups with doses from 125 up to 500 mg/kg. In the female groups, the loss of Hgb and rise in the Cl were noted in the doses higher than 500 mg/kg while the loss of WBC was noted in almost all the treated groups. However, none of these changes was suggestive of specific abnormalities when compared with the photomicroscopic findings and our hematological background data. 2. There were no significant changes in the general conditions of any group of rabbits. Their mean body weights and their mean feed intakes proceeded almost similarly with those of the control group. In the hematological and histopathological tests also, no specific abnormal finding was experienced, which were deemed to be attributable to the administration of FOM-Na.


[Ultrastructure of the microcirculatory pathways of the lungs in chronic penumonia].

Study of the ultrastructure of the microcirculation tract in patients suffering from chronic pneumonia with bronchiectasis and abscess formation revealed involvement of all parts of the pulmonary and pleural microcirculation system, including intra-and extravascular disorders and changes in the vascular wall. Combination of rheological disorders and dyscoagulation in the microvessels with stable increase in vascular permeability and changes in the components of the aerohematic barrier leads to disturbances of metabolic and hemodynamic homeostasis in the lungs, advancement of the suppurative process, and increase of pulmonary hypertension.


[Problem of pulmonary hypertension in determining the indications for an operation in congenital heart defects].

The authors studied the indications for surgical treatment of patients with congenital heart diseases and increased pulmonary blood flow, depending on the degree of pulmonary hypertension. Particular attention is focused on the indications for operation in ventricular septal defect. The work is based on the experience of the workers of the institute, embracing 3,521 operations performed on this category of patients among whom there were 863 children under 3 years of age. The indications for surgery are determined in conformity with clinico-hemodynamic groups according to a classification elaborated at the institute. The late results studied in 213 patients in follow-up periods of up to 12 years show that the main evidence of the efficacy of surgical treatment are the hemodynamic data, which determine the prognosis and the subsequent working capacity of the patients.


[Evolution of lesser circulation hypertension in patients with congenital heart defects based on the example of an interventricular septal defect].

The results of direct pressure measurement in pulmonary circulation in 452 patients with ventricular septal defect (216 males and 236 females), whose age ranged from 12 months to 37 years, were analysed. The findings of diagnostic catheterization of the heart in 150 practically healthy persons 12 months to 40 years of age were used to elaborate the normal values of pressure in pulmonary circulation. The results of pressure measurement in pulmonary circulation repeated at intervals of 1 to 6 years in 46 patients with ventricular septal defect, 18 months to 23 years of age, were analysed. Reverse evolution of pressure in pulmonary circulation after surgical rehabilitation was followed up in 85 patients in 1, 2, 3, 5, and 7 years after the operation. At the age of 12 months to 7 years, systolic pressure in the right ventricle and pulmonary artery comes down to a possible minimum due to expenditure of the adaptational reserve. In large ventricular septal defects, however, the organism proves incapable of reducing the pressure in the early and first periods of childhood as a rule, and so the pressure increases throughout life.


[Characteristics of the pathogenesis of pulmonary hypertension and the formation of cor pulmonale in the basic forms of chronic nonspecific lung diseases].

A group of 206 patients with the main forms of chronic nonspecific diseases of the lungs (chronic bronchitis, chronic pneumonia, and bronchiectasis--local and diffuse) was studied. The condition of pulmonary ventilation, bronchial patency, and hemodynamics of pulmonary circulation were analysed. Comparison of the data obtained in different groups of patients made it possible to determine the main peculiarities of the pathogenesis of pulmonary hypertension and formation of cor pulmonale.


[Myocardial contractile capacity of the right ventricle in lesser circulation hypertension and in right ventricular insufficiency].

The informative value of some indices of myocardial contractility, calculated from curves of pressure in the right ventricle and pulmonary artery, was determined in 119 patients suffering from mitral heart disease with various grades of pulmonary hypertension in 25 patients who did not have a heart disease. The dependence of these indices on the grade of pulmonary hypertension and severity of the clinical symptoms of right-ventricular insufficiency was also studied. The Siegel-Sonnenblick contractility index proved to be the most informative index of myocardial contractile function. It was reduced in patients with right-ventricular insufficiency. With an increase in pulmonary hypertension, the average rate of increase in intraventricular pressure in the phase of isovolumic contraction grows sharply, which indicates to considerable hyperfunction of the right ventricle.


[State of the indices of external respiration and hemodynamics in the greater and lesser circulations in hypertension].

Six hundred and ninety patients with hypertensive disease and 37 with hypertensive disease and concomitant chronic pneumonia were examined. It was found that, besides disorders of hemodynamics in systemic circulation, circulatory disorders in pulmonary circulation and disturbances in external respiration develop due to increased tonus of the vessels of the pulmonary artery system and pulmonary arterial hypertension. These disorders appear before the development of left-ventricular insufficiency and increase with the progress of the disease, and their degree correlates with the degree of arterial hypertension of systemic circulation. Concomitant cardiovascular insufficiency aggravates these disorders.


[State of the myocardial contractile function of the right sections of the heart and of the pulmonary hemodynamics in liver cirrhosis (based on clinical instrumental and morphological study data)].

The state of pulmonary hemodynamics and the contractile function of the right parts of the heart were studied clinically and instrumentally in 35 patients with diffuse chronic pathological conditions of the liver. The lungs and heart were examined morphologically in 24 persons who had died from cirrhosis of the liver in the edematous-ascitic stage. Pulmonary hypertension was found to be directly dependent on the degree of the diffuse affection of the liver. Secondary-compensatory changes in the contractile function of the myocardium of the right parts of the heart in response to increase of pressure in the pulmonary artery in patients with cirrhosis of the liver were proved to occur.


[Sanatorium stage in the rehabilitation of patients with rheumatic defects after heart valve prosthesis].

In 93.2% of 104 patients treated at a cardiological sanatorium after heart valve prosthetics the condition had improved by the time of discharge and only in 2.9% (3 patients) it had grown worse. The measures of rehabilitation comprised curative, physical, and psychologic aspects. The improvement in the condition of patients who had been operated on was attested by the results of ECG, polycardiography, and external respiration tests. The increased tolerance to physical load and the improved ability for coping with the tasks of every-day life are also objective indicators of the effectiveness of the stage of sanatorium treatment in the general complex of rehabilitation of patients who had been subjected to heart valve prosthetics.


[Changes in the cholesterol metabolism during electric stimulation of the skeletal muscles].

The effect of electric stimulation of the skeletal muscles on the content of cholesterol and atherogenic lipoproteins in blood serum, tissues, and bile was studied in experiments on rats subjected to long-term fixation and kept on an atherogenic diet. It is shown that electric stimulation of the muscles leads to a decrease in the content of cholesterol and atherogenic lipoproteins in blood serum and an increase in the tissue cholesterol content.


[Effect of hypokinesia on the contractile function of the myocardium].

Rats were subjected to hypokinesia for two months and the contractile function of isolated papillary muscles was studied. Hypokinesia reduced significantly the isotonic contraction velocity which depended on the ATPase activity of the myofibrils; it also reduced the velocity and index of relaxation which depended on the functional capacity of the Ca++-pump of the sarcoplasmic reticulum. The maximum force of isometric contraction determined by the quantity of actomyosine bridges in the myofibrils did not change after hypokinesia. This complex of changes is contrary to that observed in adaptation to exercise, when the velocity of isotonic contraction and relaxation increases while the force of isometric contraction does not change. The possible mechanism of this stability of the contractile force during adaptation and readaptation of the heart is discussed.


[Internal organs as a blood depot during different extreme exposures].

The results of an experimental study of fluctuations in the relative content of blood in 15 internal organs on exposure of the intact organism to the effect of various factors are discussed. A total of 25 experimental series was conducted, with 14 animals used in each series. Four types of regional blood redistribution reactions were distinguished according to the changes in blood filling (in the brain, heart, liver, and other organs of the abdomen and true pelvis). In most cases these reactions are accepted as a sign of mobilization of the dynamic intravascular blood reserve from the large-capacity vessels, mainly of the abdominal organs and organs of the true pelvis, with or without the participation of the liver, and also as a sign of utilization of the "reserve" blood in organs and tissues experiencing functional stress. The results of correlative analysis bear evidence of the reciprocal character of fluctuations in the amount of blood during stress, in the brain, lungs, and heart on the one hand and in the organs of the abdomen and true pelvis on the other, and also testify to the autonomous character of changes in the amount of blood in the liver. The internal organs of the abdomen and true pelvis are not a functionally single vascular region.


[Effect of adaptation to physical load on the efficiency of oxygen utilization by the heart].

The mechanical performance, oxygen consumption, and external efficiency of isolated working hearts taken from control and trained rats were studied. Elevation of calcium concentration in perfusate from 1.25 to 2.5 mm and increase in external work were noted in the hearts of both the groups. This increase in the trained hearts was two-and-a-half times of that in the control rat hearts, while oxygen consumption was equally elevated in both the groups. As a result the efficiency of oxygen utilization by the heart for external work was higher in the trained hearts than in the controls. The results obtained may be explained by the greater functional power of the calcium transport system in the myocardial cells of trained animals.


[Glycoproteins: their biological and clinical significance. I (author's transl)].

Increasing knowledge on structure, biosynthesis and catabolism of glycoproteins have given new insights on the patho-biochemical and clinical significance of these macromolecules. The most important results and conclusions are summarized in this review. 1. The terminal sugars of glycoproteins--N-acetylneuraminic acid (NANA) and L-fucose--as well as the penultimate galactose molecule have important functions in cell interaction, adhesion and recognition. Moreover, these carbohydrates mediate the migration and distribution of cells and it is believed that they are essential part of the feto-maternal "immunological barrier". 2. Evidence indicating that the composition and pattern of plasma membrane glycoproteins is associated with tumour growth and metastatic formation is accumulating. Moreover, the determination of serum glycosyltransferase activity is gaining increasing interest, because the level of these enzymes is substantially elevated in patients with neoplastic disease. 3. Diseases of the autoimmunosystem are likely linked to a disturbed glycoprotein metabolism. The clinical importance is underlined by studies on immunotherapy of tumours.


[Digoxin induced changes in the exercise ECG and its relation to plasma concentrations (author's transl)].

The effects of a single intravenous dose (1.5 mg) of diogoxin on the resting and exercise ECG were studied over several days in twelve normal subjects. Maximal ST-segment and T-wave changes were observed 24 h after drug administration. A significant ST-segment depression and decrease in T-wave amplicude were still observed on the 7th and 11th day after the glycoside dose, in spite of undetectable digoxin plasma concentrations. There was no correlation between digoxin plasma concentration and ECG-changes. In order to avoid false positive ischaemic ST-segment responses to exercise, a therapy with digoxin should be discontinued for at least 2 weeks before the exercise test.


Disassembly of microtubules in the Lesch-Nyhan Syndrome? (Lesch-Nyhan syndrome and microtubules).

The Lesch-Nyhan syndrome is an unusual disease. It combines neurological disorders, behavioural disturbances, metabolic changes and haematological symptoms. The syndrome is caused by an X-chromosomal transmitted enzyme deficiency of the 'salvage pathway' in purine metabolism. The hitherto unexplained pathogenesis was the reason for investigations into metabolism and morphology of the blood cells of a patient suffering from the syndrome. Along with the defect in guanine nucleotide resynthesis there was a defect of microtubules in platelets and a sphaerocytosis in red cells, which could be the result of a disassembly of structural proteins. The development and maintenance of the highly heteromorphic structure of nerve cells and the neuronal function including axonal transport of cell organelles and transmitters is dependent on microtubules. Thus a disassembly of microtubules could be the mechanism in the pathogenesis of this complex syndrome.


Elimination of ampicillin and gentamicin by hemofiltration.

Elimination of ampicillin and gentamicin by hemofiltration was measured in 5 and 4 patients, respectively, being treated for end stage renal failure. Serum half-life time of ampicillin after a single I.V. dose of 2 g, was found to be 2.97 +/- 0.73 h, and the filtrate concentrations declined parallel to the serum ampicillin levels, as was to be expected. The serum half-life time after a single I.V. dose of 1 mg/kg body weight gentamicin was 3.26 +/- 0.42 h, and considerably shorter than T/2 of gentamicin in conventional hemodialysis, while the filtrate concentrations increased paradoxically with declining serum levels. This could be explained by binding of this aminoglycoside to the polyacrylnitril membrane of the RP 6 dialyser used for hemofiltration.


[Changes in the soleus muscle tissue metabolism of rats after a flight on the Kosmos-690 biosatellite].

The soleus muscle of flown rats did not show any effect of gamma-irradiation on the composition and enzymic activity of protein fractions. On the Ist postflight day a significant decrease in the content of myofibrillar and sarcoplasmatic proteins in the soleus muscle was found. Besides, a drastic increase in the activity of aspartate aminotransferase and lactate dehydrogenase of sarcoplasmatic proteins and an atrophic type change in the LDH pattern were demonstrated. Those changes were similar to the weighttlessness-induced processes of atrophy and dystrophy and proved reversible.


[Morphological study of the adrenals of rats exposed on the Kosmos-690 satellite].

Adrenals of 12 rats flown aboard the biosatellite Cosmos-690 and 30 rats used in the ground-based experiments Control-1 and Control-2 were studied morphologically. The animals were sacrificed on the 2nd and 27th days after completion of the experiments (i. e., on the 12 and 37th days after irradiation at a total dose of 800 rad). A comparative study of morphological changes in the adrenals of flight and control rats did not show any distinct differences. It is therefore concluded that space flight factors did not produce a significant effect on the adrenal response to irradiation at a dose of 800 rad.


[Antiorthostatic hypokinesia as an approximate model of weightlessness].

Eight test subjects were exposed to a five-day bed rest experiment in the recumbent and head-down position (at an angle of 0 degrees,--4 degrees,--8 degrees, and--12 degrees) to study the physiological effects of the exposure. The head-down tilting at--4 degrees and--12 degrees was shown to simulate physiological effects of real space flight better than bed rest at 0 degrees. The results made it possible to model an acute stage of weightlessness adaptation and to assay the contribution of gravity-induced blood redistribution to the physiological reactions.


[Bioelectrical activity of the brain during 49-day antiorthostatic hypokinesia in persons with the early signs of autonomic vascular dysfunction].

Cerebral bioelectric activity of 18 male test subjects (9 test subjects with early manifestations of autonomic-vascular dysfunctions of the hypertensive, hypotensive or cardiac type, and 9 healthy test subjects), aged 25 to 42, was studied during their 49-day head-down tilting (-4 degrees) and during recovery. On the 5th experimental day their EEG showed signs of CNS irritation and increased excitation in response to photostimulation. That was very marked in the test subjects with autonomic-vascular dysfunctions. On the 15, 30 and particularly 45th experimental day their EEG showed both diffusion and paroxysmal slow activity; CNS excitability decreased significantly during rhythmic photostimulation. By the 20th--22nd day of recovery EEG parameters returned to normal. This indicates that the changes were reversible and that the therapeutic measures applied were effective.


[Effect of a 49-day space flight on immunological reactivity indices and on the blood protein makeup in the crew of Saliut-5].

The prolonged 49-day space flight resulted in a significant inhibition of immunological reactivity of the Salyut-5 crewmembers which involved a decline in bactericidal activity of the serum and lysozyme activity of the saliva, and a decrease in the content of immunoglobulins in the saliva and tonsillary lacunae. After the flight recovery of reduced immunoreactivity took a longer time than after shorter-term flights. The prolonged space mission led to an increase of most globulin fractions and a decrease of albumin in blood. With respect to globulin fractions, a predominant increase in the content of C3c and C4-factors of the complement and immunoglobulins G, A, M was noted. Blood proteins returned to normal within a long period of time.


[Blood coagulation factors of the vascular wall and myocardium in hypokinesia in rabbits].

The effect of hypokinesia on the hemocoagulatory and fibrinolytic properties of aorta, myocardium and venae cavae was studied. Hypokinesia decreased thromboplastic activity of the intima and increased that of the mid- and outer layers of the aorta. Anticoagulatory properties of aortal and myocardial tissues increased whereas their antithrombin properties decreased. Rabbit immobilization increased the content of fibrinolytic stimulants in the aorta and myocardium.


[Effect of hypokinesia on the resistance of animals to the action of chemical substances].

Resistance of rats exposed to 20-day hypokinesia to high concentrations of vapors of ethylacetate, dioxan, and liquid fluorochlorocarbon was studied. As compared with controls, lethality of the hypokinetic animals increased upon ethylacetate and dioxan breathing and decreased upon intoxication with liquid fluorochlorocarbon. The hypokinetic animals showed decreased resistance to chronic effects of ethylacetate and perfluorated ester vapors (at a concentration of 10 and 100 mg/m3 for 90 and 30 days, respectively). This was suggested by functional and pathomorphological studies.


[Change in the properties of the femoral bones of rats due to exarticulation of the crus and hypokinesia].

Rat experiments demonstrated that unilateral calf exarticulation leading to the loss of the leg weight-bearing function resulted in a decrease of the density, ash content and mineral content in the femoral diaphysis. This manipulation reduced the mechanical strength and did not change the elastic properties of the bone. Histological examinations showed osteoporosis in the cortical plate. Partial maintenance of the weight-bearing function in the animals with bilateral exarticulation of the calf prevented these changes. The results suggest that special steps taken to provide static load on leg may be effective countermeasures against atropic changes in bones devoid of their weight-bearing function.


[Change in the content and makeup of the phospholipids in the microsomal fraction of rat skeletal muscles under the influence of a flight on the Kosmos-690 biosatellite].

The content and composition of phospholipids in the microsomes isolated from the back femoral muscles of rats flown for 20.5 days aboard the biosatellite Cosmos-690 were studied. Gamma-irradiation applied in the ground-based control experiments did not change the amount of total phospholipids in microsomes of skeletal muscles and altered insignificantly the content of their individual fractions. On the 2nd postflight day a substantial increase in the content of total and fractional phospholipids in microsomes was found. The decrease seems to be induced by weightlessness. On the 26th postflight day the content of total phospholipids returned to the normal whereas their fractional composition still remained changed.


[Effect of prolonged unidirectional migration of the sleep--wakefulness rhythm phase on human physiological functions, mental productivity and sleep].

The paper gives the results of three 30-day experiments carried out to study the effect of migration of the sleep--alertness cycle on physiological functions, psychic productivity and sleep of man. The migration was agravated by the initial change of the cycle which varied from +/- 7 to +/- 11 hours. All test subjects showed a counter-clockwise migration which amounted to a 1.5 hour shift every 4-5 days. All test subjects demonstrated functional cerebral changes, decline of psychic productivity and sleep disorders. The level of those disturbances depended on the value of the initial shift of the sleep--alertness cycle and on the cumulation of the migration effect. Those disorders were noted even when the prechanged sleep--alertness cycle approximated the normal pattern as a result of migration. The results indicate that the migrating day--night pattern, particularly in combination with the initial shift of the sleep--alertness cycle, cannot be recommended for manned space missions. Good health condition and high work capacity of cosmonauts can be maintained, only if a 24-hour sleep--alertness cycle with a normal sleep pattern is provided.


[Cerebral hemodynamics and the functioning of the visual analyzer after intensive light exposures].

Non-anesthetized rabbits were exposed to short-term intensive photostimulation. The experiments showed that the resultant increase in cerebral circulation occurred independently from systemic circulation, cardiac and respiratory function. Simultaneously, substantial adaptive changes in the optic system measured by electroretinography and optokinetic nystagmus developed.


Interference of tris(hydroxymethyl)aminomethane with structure and function of Golgi membranes.

Short term perfusion of isolated rat liver with tris(hydroxymethyl)aminomethane or other nonamphoteric amines (glycine amide, diethylamine) in moderate concentrations (10 to 20 micron) causes blistering of Golgi stacks on the concave side as well as swelling of lysosomes and of secretory vesicles in otherwise unaltered hepatocytes. Similar vacuolization is observed in Kupffer cells, pancreatic beta-cells, intestinal epithelial cells, and renal proximal tubule cells, but not in alpha-cells of the pancreas or in kidney glomerular podocytes. Fusion of the vesicles occurs frequently and involves denudation of intramembranous particles from contact areas. Since protein synthesis is not affected, inhibition by tris(hydroxymethyl)aminomethane of protein secretion into the perfusate indicates a block in protein processing at a postribosomal level. This finding together with morphologic evidence unravels the Golgi and post-Golgi membranes as specific site of tris(hydroxymethyl)aminomethane interaction with intracellular structures.


[Ergometric studies in the practice of medical aviation expertise].

In order to assess standard and relative indices of ergometry, exercise tolerance and physical work capacity, 64 members of flight crews with compensated atherosclerotic coronary cardiosclerosis (aged 28 to 56) were examined. The studies were carried out using the Siemens cardiopulmonary complex at rest, at work load of 100 Wt/min for 5 min and during recovery for 10 min. At the initiation of the experiment and during recovery ECG in 12 standard leads was recorded every other minute. With respect to the age and clinical data, the test subjects were subdivided into two groups. Electrocardiographic study revealed insufficiency of coronary circulation in 63.7% of the first group and in 80,6% of the second group test subjects. Ergometric measurements showed a distinct decrease of the chronotropic, inotropic and aerobic cardiac reserves, especially of the second group test subjects. Ergometric parameters correlated well with the clinical and electrocardiographic data. The results can be used in the diagnostics, evaluation of cardiopulmonary functional and reserve capabilities, and support of expertise recommendations.


Neuronal and oligodendroglial infection by the WW strain of Theiler's virus.

Newborn ICR mice were infected by intracerebral inoculation of 10(5.3) LD50 of the WW strain of Theiler's virus and examined serially by virologic and ultrastructural methods. Maximal titers of 10(6) LD50 developed in the brain by day 8 when 90 per cent of the animals were dead or moribund. The virus first appeared and was most prominent in the thalamus, basal ganglia, and midbrain. It spread from these areas throughout the cortex, brainstem, and spinal cord but spared the cerebellar cortex. Both neurons and oligodendroglia were infected. Infected cells first showed dispersion of polyribosomes, accumulation of vesicles, and widening of perinuclear cisternae. Normal cytoplasmic organelles and the nucleus were displaced by an accumulation of viral crystals, membranous profiles, and fibrillar material. Within degenerating cells the nuclear chromatin became clumped and marginated and the cytoplasm was filled either with vesicles or masses of paracrystalline viral arrays. These changes were accompanied by a vigorous inflammatory response of lymphocytes, plasma cells, macrophages, neutrophils, and eosinophils. Lysis of oligodendroglia during acute infection with the WW strain of Theiler's virus may provide a stimulus for the late autoimmune demyelination that has been described in animals that survive the acute encephalitis.


[Effect of space flight on the course of radiation lesions in the lymphoid organs of rats].

The spleen, thymus and inguinal lymph nodes of rats exposed to a prolonged (24 hours) irradiation at a dose of 800 rad on the 10th day of the 20-day space flight aboard the biosatellite Cosmos-690 were examined histologically and cytologically. The lymph organs showed the changes typical of radiation-induced lesions. They did not display an aggravating or modifying effect of space flight factors on the development of radiation-induced lesions in lymph organs. It is emphasized that radiation-induced lesions at the above irradiation dose may mask weightlessness-induced effects in lymph organs.


The collagen network of the heart.

An extensive collagen skeleton in the myocardium is clearly demonstrable by scanning electron microscopy. This system mechanically connects myocytes to contiguous myocytes, connects myocytes to contiguous capillaries, and is responsible for orienting myocytes into anatomical units. The extent and location of the system involves it in a variety of physical parameters of the heart under both normal and abnormal conditions. The myocyte to myocyte collagen struts may provide for sarcomere alignment from cell to cell, ensure equal stretch of contiguous cells, and prevent slippage of adjacent cells. The numerous myocyte to web network connections would ensure that the entire group of cells function in a consistent fashion. The origin and course of the myocyte to capillary collagen struts could account for capillary patency during systole in the presence of high ventricular wall pressures. The complex web network surrounds groups of myocytes and is mechanically coupled to the contained myocytes. The loose collagen connections between groups easily permits slippage and rearrangement of groups of cells as expected in acute dilation. The web network itself could be the site of some of the viscoelastic properties of the heart.


In vivo responses to inhaled proteins. II. Induction of interstitial pneumonitis and enhancement of immune complex-mediated alveolitis by inhaled concanavalin A.

An animal model of environmental lung disease is described in which phytomitogen, antigen, or both, are administered in aerosol form to previously immunized or immunologically naive rabbits. Inhalation of concanavalin A alone induced an interstitial pneumonitis in nonimmunized rabbits. Inhalation of concanavalin A alone induced an interstitial pneumonitis in nonimmunized rabbits. Inhalation of bovine serum albumin (BSA) alone typically produced only focal eosinophilic granulomas in BSA-immunized animals, and no injury whatever in nonimmune animals. However, simultaneous administration of BSA-concanavalin A aerosol mixtures to BSA-immunized rabbits induced a severe interstitial pneumonitis and granulomatous vasculitis, together with areas of frank parenchymal necrosis. When repeated on a chronic basis over a 4- or 8-week interval, challenge with BSA-concanavalin A aerosols resulted in both acute necrotic lesions as well as areas of frank interstitial fibrosis. Necrotic foci in acutely injured lungs were associated with interstitial deposits of BSA, rabbit anti-BSA antibody, and complement. Electron microscopy revealed numerous neutrophils within the pulmonary interstitial spaces of these animals, often in association with collagen and elastin fibers. The pattern of injury in immune rabbits induced by antigen-concanavalin A aerosols, in its nonnecrotizing form, is consistent with that of an extrinsic allergic alveolitis. However, the severe, necrotizing form of acute injury closely resembles changes seen in Wegener's granulomatosis. Possible mechanisms of injury produced by antigen and phytomitogen inhalation are discussed.


The cardiac component of the orienting response: effects of signal intensity, clinical interpretation, and procedural limitations.

The effects of stimulus intensity on the cardiac component of the orienting response were explored in male and female subjects. The acoustic stimuli were 10 recorded repetitions of an identical consonant vowel cluster spoken by an adult male. Heart rate data were obtained for both subject groups at three sensation levels across the baseline heart rate and at 10 stimulus presentation trials. A significant main effect was noted for trials. Significant linear and quadratic trend components were observed, reflecting habituation of the orienting response as a function of trials, and indicating the nonmonotonicity of heart rate change over trials. A lower mean heart rate was observed for Condition Two (20 dB SL) than for either of the other conditions, 10 dB and 30 dB SL respectively. Analysis of group variability and individual subjects' heart rate data suggested limitations in generalizing from group to individual data, as well as a need for further investigation if proper interpretation of single subject heart rate data are to be useful in the clinical situation.


Utilization of a central auditory processing test battery in evaluating residual effects of decompression sickness.

Six professional divers were examined as patients who presented peripheral auditory, vestibular, or central symptoms attributed to incidents which occurred while diving. Each diver received a central auditory processing (CAP) test battery consisting of: (1) a dichotic sentence listening task, (2) a monotic filtered word task, (3) a binaural fusion task, and (4) an alternating speech task. The CAP test results, in all cases substantiated other neurological/vestibular test battery results which we have reported in detail previously.


Evaluation of relationship between hearing threshold and loudness discomfort level in sensorineural hearing loss.

The relationship between hearing level and loudness discomfort level (LDL) for narrow-band noise was evaluated in two groups of patients with sensorineural hearing loss. Group I had thresholds ranging from 25-60 dB SPL and Group II's thresholds ranged from 65-100 dB SPL. LDLs were determined for narrow bands of noise centered at 500, 1000, 2000, and 4000 Hz. The LDLs for Group II were greater than those for Group I and the differences were statistically significant. It is speculated that one reason for others not finding differences as a function of hearing level may be the absence of severe to profound hearing loss in the test populations.


Suggested threshold sound pressure levels for frequency-modulated (warble) tones in the sound field.

The problems inherent in using frequency-specific stimuli in the sound field to determine threshold sensitivity are reviewed, including a discussion of some of the specific problems encountered when introducing pure tones, narrow bands of noise, and frequency-modulated (FM) tones. The results of two experiments are reported. In Experiment I, the relationship between pure tones and frequency-modulated tones is developed under earphones in an anechoic chamber, and in two sound-isolated auditory test rooms (not anechoic). Experiment I resulted in the development of a reference threshold sound pressure level for frequency-modulated signals in the sound field. In Experiment II the reference level was applied to a clinical test facility and evaluated with a group of hearing-impaired individuals. The results suggest that the sound-field reference levels accurately reflect monaural threshold under earphones, when the earphone is calibrated to the ANSI, 1969 standard, and the sound field is calibrated to the suggested standard.


The dysarthrias of Shy-Drager syndrome.

Shy-Drager syndrome is a degenerative disease of the central nervous system that may include among its signs some form of dysarthria. Of 80 patients with Shy-Drager syndrome, 35 presented some form of dysarthria. Of these, 15 presented dysarthria indicative of cerebellar dysfunction, 11 with dysarthria indicating involvement of the striatum, and nine with various mixed dysarthrias indicative of multiple motor system involvement. The results of this study reaffirm the value of assessing motor speech in the differential diagnosis of neuromotor impairments and emphasize the importance of maintaining effective modes of communication for patients having progressive disorders.


Three experiments on the California Consonant Test.

Three experiments were conducted using the California Consonant Test (CCT). Initially, performance-intensity functions were obtained for both normal hearers, and those with high frequency sensorineural hearing loss. Results demonstrated almost a linear function for both subject groups (approaching asymptote at 50 dB SL) as compared to the typical sigmoidal function obtained with conventional word recognition tests. Experiment II compared results of the CCT to those of the N.U. No. 6 lists in 60 subjects with high frequency hearing loss. Consistent with previous findings, relatively high word recognition scores were obtained for the NU-6 materials whereas the range of scores on the CCT approximated a normal distribution. Experiment III examined the internal consistency and split-half reliability of the CCT. Despite significant (p less than or equal to 0.05) correlation coefficients, the wide variability between half-list scores among individual listeners doses not support the use of half-list testing.


Psychometric characteristics of the WISC-R Performance Scale with deaf children.

The WISC-R Performance Scale was administered to 59 prelingually deaf children. The internal consistency reliability to four of subtests and the Performance IQ were assessed anf found to be similar to the reliability reported by Wechsler (1974) with the standardization sample. Two aspects of criterion-related validity were computed. Concurrent validity as demonstrated by the correlation with the Hiskey-Nebraska Test of Learning Aptitude was found to be adequate. Predictive validity as defined by the correlation with achievement test results was also computed. Statistically significant correlations were found for six of the eight achievement areas. Implications for use are discussed.


Application of visual reinforcement audiometry (VRA) to low-functioning children.

Visual reinforcement audiometry (VRA) was studied on a group of low-functioning children in an ongoing clinical program. After establishing the specific reinforcing value of the visual stimulus, threshold assessments were made. VRA was an effective test procedure for most of the children tested, providing their developmental ages reached approximately the 10-month level or higher. On the basis of VRA thresholds and tympanometry, 52% of the children seen were referred for medical evaluation. A variation of VRA was used to assess syllable-discrimination performance on a pilot basis. Results are discussed in terms of the potential use of VRA to assess infant spedch-sound discrimination in addition to its current use as an indicator of hearing sensitivity.


The Hearing Handicap Scale as a measure of hearing aid benefit.

Use of the Hearing Handicap Scale as a measure of hearing aid benefit was investigated. New hearing aid users with bilateral, sensorineural hearing losses ranging from 5 dB HL to 55 dB HL served as subjects. Changes in speech reception threshold, word identification, and Hearing Handicap Scale were derived by comparing data obtained prior to hearing aid use with that obtained following four weeks of hearing aid use. Results showed a significant improvement for all three measurements and indicated that improvement in word identification presented at conversational level was more related to self-reported hearing aid benefit than was improvement in speech reception threshold. Also, word identification ratings obtained with the stimuli presented at conversation speech level produced a significant correlation with Hearing Handicap Scale scores.


Rheumatoid pericarditis. Clinical significance and operative management.

The incidence of subclinical pericarditis associated with rheumatoid pericarditis may be as high as 50 percent, but significant impairment of cardiac performance owing to this type of pericarditis rarely occurs. In the past 7 years, we have encountered eight men with congestive heart failure owing to rheumatoid pericarditis. Cardiac catheterization and echocardiography were useful in establishing the diagnosis of pericardial constriction. Pericardiocentesis was unsuccessful in relieving symptoms in the three patients in whom the procedure was performed. Seven patients underwent pericardiectomy; six had constrictive pericarditis and one patient had an acute pericarditis with the sudden onset of cardiac tamponade. The other patient died of cardiac tamponade prior to operation. All patients improved after operation and have remained free of cardiac symptoms 3 months to 4 1/2 years later. The frequent occurrence of adhesive and obliterative pericarditis with loculated effusions suggests the need for pericardiectomy rather than pericardiocentesis in the patient with rheumatoid arthritis and symptomatic pericardial involvement. Immediate and lasting relief of this unusual nonarticular manifestation of rheumatoid arthritis can be expected after pericardiectomy.


Use of biological glue in acute aortic dissection. Preliminary clinical results with a new surgical technique.

Use of a biological glue (GRF) is common in certain fields such as hepatic or renal surgery, but its use in vascular surgery, especially in acute aortic dissection, has not yet been reported. Our experience has demonstrated many advantages: The glue is very simple and safe to use. The aortic tissues are firmly reinforced and the sutures tighten immediately. The proximal aortic stump is anatomically reconstructed, and generally the aortic valve can be preserved and coronary reimplantation avoided. The preoperative and postoperative bleeding rates are low and the postoperative course generally is simple. The risk of maintenance or recurrence of the dissection process is reduced. Consequently, the hospital mortality rate can be reduced to about 10 percent and the long-term survival rate greatly improved.


Detection, localization, and treatment of occult bronchogenic carcinoma in nickel workers.

Asymptomatic men exposed to nickel sulfide prior to 1963 were studied prospectively to investigate cytologic abnormalities in the sputum. We discovered a considerably greater incidence of squamous cell tumors that would have been expected from subjects exposed only to cigarette smoke.


Decision-making in repair of tetralogy of Fallot based on intraoperative measurements of pulmonary arterial outflow tract.

The equation that we proposed in this JOURNAL (1977), relating the postrepair ratio between peak right ventricular pressure and peak left ventricular pressure (PRV/LV) to the intraoperatively measured internal diameter of the narrowest point in the pulmonary arterial outflow tract (formerly called pulmonary "anulus"), performed well when prospectively tested in 25 patients undergoing repair of the tetralogy of Fallot. The observed PRV/LV in all 21 patients in whom no transannular patch was used fell within the 70 percent confidence limits (1 standard deviation) of that predicted from the measured diameter. A trivial difference (-0.03 +/- 0.069 PRV/LV units, P = 0.08) was found between predicted PRV/LV and that observed after repair, with body surface area (BSA) used for normalization. When the four additional patients who had secondary transannular patching are included, or where the normalization was with weight, the differences were not significant (p greater than 0.2). A slightly revised equation has been devised using the combined data from our original group and the patients used for prospective testing. This equation predicts with reasonable accuracy (r = -0.69, p less than 0.0001) postrepair PRV/LV without transannular patching from the intraoperatively measured diameter of the pulmonary arterial outflow tract. We believe it is therefore helpful in the operating room in making the important decision for or against using transannular patching.


Morphologic and functional effects of esophageal cryotherapy.

With advances in equipment design, cryotherapy has been applied increasingly in the management of various integumentary disorders. Recently, endobronchial cryotherapy has been utilized in the treatment of acquired tracheal strictures. To evaluate the effects of cryotherapy upon the esophagus, we cooled the distal esophagus of 12 cats to -70 degrees to -80 degrees C. for 2 minutes with a specially constructed cryoprobe. The animals were put to death in pairs 90 minutes, 4 days, 10 days, 14 days, 28 days, and 42 days following cryotherapy. Immediately prior to sacrifice, all animals were studied with esophageal cinefluoroscopy and esophageal manometrics. All animals tolerated this degree of cryotherapy and gained weight on an ad libitum diet. Manometric studies demonstrated diminished amplitude of peristalsis immediately following cryotherapy, but prompt return to a normal manometric pattern. There was no evidence of esophageal dysfunction on esophageal cinefluoroscopy. Morphologic examination demonstrated superficial ulceration between 4 and 10 days following cryotherapy, with subsequent healing. The esophagus in animals put to death 28 and 42 days following cryotherapy appeared histologically normal. These studies demonstrate the safety of cryotherapy to -70 to -80 degrees C. upon the esophageal wall and suggest investigation of the usefulness of this modality in the treatment of local esophageal webs and strictures.


Intrathoracic lipomas. Report of three cases and review of the literature with emphasis on endobronchial lipoma.

Intrathoracic lipomas are rare, benign neoplasms of unknown origin, with symptoms depending primarily on their location and size. They frequently represent on incidental roentgenographic finding and are clinically significant in that they may simulate malignant tumors and, when located endobronchially, may cause irreparable lung damage. Three cases of intrathoracic neoplasms are reported herein, and the English literature on the subject reviewed. In some cases, bronchoscopic examination may yield the diagnosis of endobronchial lipoma but, in general, thoracotomy is required for diagnosis. A more complete classification is suggested and the preferred mode of treatment is discussed.


Cardiac rhythm disturbances during fiberoptic bronchoscopy: a prospective study.

Twenty-six patients undergoing transnasal fiberoptic bronchoscopy (FOB) were electrocardiographically monitored for 12 hours before, during, and 12 hours after bronchoscopy. We measured arterial lidocaine concentrations during the procedure as well as arterial blood gases before and after the procedure. The incidence of total arrhythmias, including sinus tachycardia, during the control period was 69 percent; minor arrhythmias, 69 percent; and major arrhythmias, 8 percent. During FOB, the incidence of total and minor arrhythmias increased to 77 and 73 percent, respectively; however, the incidence of major arrhythmias decreased to 4 percent. Arterial lidocaine concentrations ranged widely, from 0.1 to 8.7 microgram per milliliter with a mean peak level of 5.0 +/- 0.6 microgram per milliliter, which was reached between 5 and 30 minutes after the insertion of the bronchoscope. We conclude that the incidence of cardiac arrhythmias, excluding sinus tachycardia, during FOB is low and that lidocaine anesthesia probably exerts a protective effect against the development of major arrhythmias during the procedure.


Earlier operation for left-sided Pseudomonas endocarditis in drug addicts.

Three consecutive patients with Pseudomonas endocarditis were treated by early operation with no deaths. The indications for operation were severe failure, systemic embolization, and infection refractory to antibiotics. The organism is aggressive, characterized by early invasion of the myocardium. Wide débridement of the anulus is necessary to remove any vegetations or intramyocardial abscessed wall. Because multiple valve infection is common, it is important to evaluate all four cardiac valves at the time of operation. Removing a second rim of the mitral anulus for separate culture at the time of mitral valve replacement may demonstrate the degree to which the valve resection has removed all infection. Early operation is necessary for reinfection of the prosthetic valve; however, metastatic abscess should also be considered in the face of continued signs of infection postoperatively. Patients should receive a 6 week postoperative course of antibiotics which have been shown by in vitro testing to be serum bactericidal in at least a 1:8 dilution. The operative findings of invasion of the myocardium by the organism and the surgical success in this small series have resulted in our recommending earlier operation in patients with these indications.


Arteriovenous ECMO for neonatal respiratory support. A study in perigestational lambs.

A study was undertaken to investigate the applicability of the arteriovenous mode of perfusion for partial support of neonatal respiration. Perigestational lambs, delivered by cesarean section, served as the animal model of respiratory distress. Arteriovenous flow was accomplished between a single umbilical artery and vein. A microchannel membrane oxygenator was used to provide partial respiratory support to the newborn lambs. Total systemic flow, pulmonary blood flow, and pulmonary vascular resistance were assessed at various rates of arteriovenous perfusion and correlated with systemic oxygenation. A reduction in right-to-left shunting of blood and pulmonary vascular resistance occurred as arterial oxygenation rose from conditions of hypoxemia to PaO2 values higher than 50 torr. Myocardial performance was not impaired at rates of arteriovenous perfusion below 30 percent of the total systemic flow, as evidenced by normal electrocardiographic tracings, pulmonary capillary wedge pressures, and central venous pressures. Arteriovenous extracorporeal membrane oxgenation (ECMO) may be particularly suitable for use in infants with hypoxia and high pulmonary vascular resistance.


Potassium-induced cardioplegia during normothermic cardiac arrest. Morphologic study of the effect of varying concentrations of potassium on myocardial anoxic injury.

Most corrective procedures as well as myocardial revascularization require a period of cardiac arrest, and numerous methods have been proposed to protect the myocardium during this ischemic episode. Potassium-induced cardioplegia is one method that appears to be of benefit in this setting. Since it is recognized that myocardial necrosis may result at very high doses of potassium, we examined the effect of varying concentrations of potassium on myocardial anoxic injury. Using an isolated rat heart preparation, we evaluated anoxic injury occurring with cardioplegic solutions containing various concentrations of K+, ranging from 15 to 200 mEq. per liter, during a 50 minute normothermic arrest followed by 60 minutes of reperfusion. The transverse  histologic sections of the left ventricular myocardium were analyzed for contraction band injury by morphometric and qualitative methods. Among the 62 animals studied the least severe anoxic injury was seen with K+ cardioplegia at concentrations of 25 and 30 mEq. per liter. At lower and higher concentrations there was little difference between the hearts exposed to anoxia with or without K+ cardioplegia. Potassium administered in very high doses, i.e., 100 or 200 mEq. of K+ per liter, led to contracture and extensive myocardial cell injury. This study suggests that potassium-induced cardioplegia is effective in reducing cell injury due to anoxia, and in this model an optimal concentration range was 25 to 30 mEq. per liter.


Myocardial depression after elective ischemic arrest. Subcellular biochemistry and prevention.

The hemodynamic and cardiac biochemical effects of global ischemic arrest during cardiopulmonary bypass (CPB) were studied in 54 animals and compared to seven animals without ischemic arrest. Ischemic arrest alone reduced the first derivative of left ventricular force of contraction (LV dF/dt) to 52 percent of control 10 minutes after resuming function and to 64 percent after 1 hour of reperfusion. Cardiac output was depressed to 52 percent of control after 10 minutes of reperfusion, and to 74 percent of control after 60 minutes of reperfusion. In six animals, moderate hypothermia (26 degrees C.) resulted in no protection of cardiac function from ischemic arrest, whereas profound hypothermia to 18 degrees C. resulted in values of LV dF/dt and cardiac output nearly equivalent to the CPB control group (no arrest). A continuous infusion of a hyperkalemic hypothermic solution slightly improved the degree of protection over hypothermia alone. The sarcoplasmic reticulum (SR) isolated from hearts which had undergone 60 minutes of ischemic arrest bound significantly less calcium when the isolation was done after 10 minutes of reperfusion as well as when it was done after 60 minutes of reperfusion. The time to spontaneous release of calcium from the SR also was significantly longer. Moderate hypothermia did not result in improved SR function, whereas deep hypothermia induced by local cooling or by hypothermic potassium infusion retained SR function at normal levels. Oxidative phosphorylation of mitochondria isolated after 60 minutes of reperfusion was also depressed. The mitochondrial respiration rate after normothermic ischemic arrest was 155 natoms of oxygen per minutes versus 237 natoms for the hypothermic hyperkalemic group. Respiratory control index was 5.5 for the normothermic group versus 9.4 for the hypothermic group. It is concluded that hypothermia, whether effected by surface cooling or by hypothermic potassium infusion, allowed full recovery of hemodynamic and biochemical functions within 1 hour of reperfusion.


Acute hypertension: its significance in traumatic aortic rupture.

Traumatic aortic rupture is a common occurrence associated with 16 percent of deaths from automobile accidents. Through a review of current literature and two recent cases from The Milton S. Hershey Medical Center, we have attempted to elucidate a common physical finding, acute hypertension associated with blunt chest trauma, and prove its significance as a diagnostic clue to traumatic rupture of the aorta. New laboratory findings of an aortic sympathetic reflex stimulated by stretching the aortic wall in the area of the isthmus provides a physiological explanation for the cause of hypertension after aortic trauma.


Placement of two transvenous permanent pacemaker leads in a single vein. Report of two cases.

In two cases of permanent transvenous pacemaker failure, the defective pacing electrode could not be removed. A second pacing electrode was placed in the same vein to avoid an additional operation. To our knowledge, this simple and effective procedure has not been previously reported.


Cardiac valve replacement in congestive heart failure due to infective endocarditis.

From January 1961 to July 1974, 138 patients underwent cardiac valve replacement because of complications of infective endocarditis. The overall operative mortality was higher in patients with Class IV cardiac functional disability (17%) than in patients with Class III (7%) or II (8%). The mortality for patients who had undergone aortic valve replacement with Class IV disability was higher (22%) than that for patients with Class III (0) or II (6%). When compared with patients without infective endocarditis who had undergone cardiac valve replacement, the operative mortality per valve replacement was approximately the same when the degree of cardiac disability was the same at the time of surgery for both groups of patients. Patients with aortic regurgitant murmurs caused by infective endocarditis should be observed closely for the onset of heart failure, especially during the first month of disease. In patients with aortic or mitral incompetence, if heart failure develops or progresses during the first month, we believe that prompt cardiac valve replacement should be considered, because even heart failure that may initially appear mild often progresses to severe heart failure during this period.


Drug abuse and dependency in patients with chronic pain.

Of 144 patients with chronic pain of nonmalignant cause, 35 (24%) were drug-dependent, 59 (41%) drug abusers, and 50 (35%) nonabusers. Codeine and oxycodone (Percodan) were most frequently abused. In regard to characteristics tested, differences between the groups were not great; but there was a significant difference in outcome between nonabuse and dependent groups. Early detection and treatment of drug abuse should minimize some of the difficulties involved in management of treatment-resistive patients with chronic pain.


Cancer of the pancreas in Olmsted County, Minnesota, 1935-1974.

All confirmed cases of pancreatic carcinoma in bona fida residents of Olmsted County, Minnesota, from 1935 through 1974 were identified and reviewed. The average annual age-adjusted incidence rates were 7.4 for males and 3.5 for females per 100,000 population. Rates increased with age for both sexes and increased slightly over the 40-year period of study, with lower incidence rates observed for rural inhabitants in the first 2 decades. At the time of diagnosis, almost 75% of patients were 60 years of age or older and adenocarcinoma was histologically identified in 92% of the cases. One-year survival was 11%, and all patients died within 3 years of the initial diagnosis. An association between pancreatic carcinoma and diabetes was noted. There does not appear to be a clear association with cholelithiasis or chronic pancreatitis. There was a high percentage (20%) of multiple primary carcinomas and an overrepresentation of metal workers observed among patients with pancreatic carcinoma.


Ceroidosis in the "brown bowel syndrome".

A middle-aged patient with "brown bowel syndrome" or gastrointestinal ceroidosis manifested as malabsorption of undetermined cause is described. Autopsy revealed involvement of the entire gastrointestinal tract and unusual cardiac findings. Microscopically, the pigment responsible for the discoloration is a lipofuchsin that is deposited in the smooth muscle cells of the gastrointestinal tract. In all reported cases, ceroidosis was associated with some abnormality of the gastrointestinal tract--that is, malabsorption, steatorrhea, or gross local disease--with the possible exception of prolonged malnutrition. This case is also unusual because of the unexplained multifocal proliferative endocarditis. Vitamin E deficiency may be the common denominator of all these various disorders.


Osteoma: an unusual cause of amaurosis fugax.

A 16-year-old white boy presented with a history of amaurosis fugax associated with an afferent pupillary defect, proptosis, discomfort of the left eye. Tomograms of the skull and of the orbit revealed a lobulated 4-cm ivory osteoma arising from the left ethmoid sinus and extending into the maxillary sinus and left orbit. After surgical extirpation, visual acuity returned to normal and the papilledema resolved after 4 months. This patient is 1 of 37 patients with osteoma of the paranasal sinuses or of the orbit (or of both) who underwent surgical treatment at the Mayo Clinic between the years 1948 and 1977. Twelve of these patients had orbital involvement, and only these patients had ocular signs and symptoms.


Primary cardiac myxosarcoma in a child.

This is a detailed clinical and autopsy documentation of a rare entity--primary cardiac myxosarcoma in a 29-month-old girl. The patient had sudden onset of right hemiplegia and angiographic evidence of multiple occlusions of the left middle cerebral artery. Subsequent M-mode and sector echocardiography showed a mobile, pedunculated left atrial tumor, which was excised. No other tumor mass was noted at the time of surgical exploration, and postoperatively, the patient received a course of chemotherapy (vincristine, dactinomycin, and cyclophosphamide). After a temporary improvement in her condition, the patient died following several days of rapid deterioration; this was 3 months after the onset of symptoms. Autopsy showed that death was due to brainstem herniation secondary to massive infiltration of the brain by tumor, and there were also widespread systemic metastases.


Development and degeneration of hearing in the C57/b16 mouse: relation of electrophysiologic responses from the round window and cochlear nucleus to cochlear anatomy and behavioral responses.

In disorders of the auditory organ associated with hearing loss, a correlation of the anatomical, behavioral and electrophysiological studies furnishes the investigator several parameters of study to better comprehend the hearing mechanism and the various anatomical structural dysfunctions that relate to the hearing loss. Mice are interesting to study because they carry several types of genes for hereditary deafness. Until recently, it was very difficult to train mice for behavioral hearing threshold testing; however, having developed such a method, the next step was to study the normal mice in these three parameters and extend the studies to mice with hereditary hearing loss. The type of mouse studied in this research was the C57/b16 strain which carries such a gene. The results of the studies indicate that the results of the behavioral and electrophysiological studies relate well to each other, and that light microscopic studies (if taken alone) do not furnish us with the actual functional capability of the structures of the inner ear. It is recommended (and it would be most valuable) that efforts should be made to collect and study human temporal bones with all three parameters of study for a better understanding of the structures of the human inner ear. Reference is made and recommendations given as to the parameters of studies while performing human electrocochleography.


Tympanoplasty: TORPS and PORPS.

We reviewed 106 cases in which PlastiPoreTM prostheses were used for ossicular reconstruction. In all cases a piece of cartilage was interposed between the prosthesis and the tympanic membrane graft to prevent the potential problem of prosthesis extrusion. With total ossicular replacement prostheses (TORPs) 55% closed to within 10 db and 85% closed to within 20 db of the bone conduction level. Closure to within 10 db of the bone conduction level was accomplished in 64% of partial ossicular replacement prostheses (PORPs) cases. These results are better than obtained previously with either ossicles or cartilage alone.


Mucoepidermoid carcinoma of the air passages: report of three cases.

A review of the literature on tumors of the small salivary and mucous glands reveals that mucoepidermoid carcinoma of the upper respiratory system is a very rare occurrence. Three such cases are reported in detail, representing 3% of all tumors of small salivary and mucous gland origin recorded by the authors over a period of 20 years. This incidence is high. Follow-up was from 3 to 12 1/2 years.


Transbronchial drainage of pulmonary abscesses with the flexible fiberoptic bronchoscope.

Flexible fiberoptic bronchoscopy with multiplanar fluoroscopic control is shown to be effective in the transbronchial drainage of pulmonary abscesses. A new technique which permits the intracavitary placement of brush forceps and fine arterial catheters is described. This has facilitated the rapid defervescence of fever and established immediate endobronchial drainage. Seventy percent of patients had complete radiographic closure of their abscess cavities at three months. Clinical findings are presented and the role of aspiration in pathogenesis of pulmonary abscess is stressed.


Spasmodic dysphonia: abductor type. A clinical report of acoustic, aerodynamic and perceptual characteristics.

Two case studies of spasmodic dysphonia (abductor type) are presented with acoustic and aerodynamic documentation. The abductor type is characterized clinically as exhibiting intermittent moderate to severe breathiness accompanied by sudden drops in pitch. These phenomena are interpreted as intermittent abductor vocal fold spasms. Complete case histories including voice therapy and their results are presented.


Wegener's granulomatosis: unusual indication for orbital decompression.

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the upper and lower respiratory tract together with glomerulonephritis. The majority of cases have ocular, sinus and ear symptomatology. A case is presented with severe granulomatous disease of the sinuses with contiguous spread to the orbit producing exophthalmos and decreased vision. An orbital decompression relieved the pressure and preserved vision. The definitive medical therapy for WG is cyclophosphamide. Emergency orbital decompression may be necessary to preserve vision in WG in patients with rapidly decreasing vision secondary to high intraocular pressure produced by the granulomatous process.


Technique for construction of facial moulage.

A technique for fabrication of a facial moulage is described which is both simple and useful in preoperative evaluation for selected facial plastic-reconstructive procedures. There are many alternative methods and materials that could be used; the one described here is the one which best suits our needs. These techniques have been used by many people for many years and no claim is being made for any innovation in this regard. However, a simple, clear, step by step explanation of this technique is described.


Epidemiology of otitis media--an interracial study.

An epidemiologic study was done comparing blacks versus whites with regard to the incidence of altered middle ear function or otitis media. Three separate groups were evaluated. All variables were controlled except for race. There appears to be statistically significant less otitis media or altered middle ear function in the black race than the white race.


Endolymphatic hydrops and otitis media.

Clinical observation of patients with fluctuant sensorineural hearing loss following or occurring with chronic otitis media led to the hypothesis that endolymphatic hydrops can result from chronic otitis media. Illustrative case reports are described. This hypothesis resulted in a temporal bone study of 560 cases in which 109 temporal bones demonstrated the presence of hydrops and 194 evidenced otitis media. Seventy-five cases demonstrated both otitis media and hydrops, of which 20 cases were selected for more detailed histopathological study. An interesting finding was the presence of apical hydrops in every case of the latter group. Statistical interpretation of this data helped rule out a coincidental or chance occurrence. A discussion of this clinical relationship included the significance of subclinical (silent) otitis media as a possible cause of endolymphatic hydrops.


The double-membrane break syndrome in sudden hearing loss.

Some patients with sudden hearing loss actually have two membrane breaks, one at the oval or round window and one further inside the cochlea. One may heal spontaneously and the other not, or both, or neither. It is very likely impossible to detect this early from the threshold audiogram, because the intracochlear breaks allows endolymph and perilymph mixing which spreads over much of the anatomically normal clchlea causing diffuse loss of function. This theory is illustrated by three case histories.


Cholesteatoma surgery: management of the labyrinthine fistula--a report of 97 cases.

Preoperative, operative and postoperative findings in 97 cases of labyrinthine fistula are presented. Most of these patients had had symptoms of chronic otitis media for 20 years or more and manifested some degree of sensorineural hearing impairment. Two-thirds had experienced dizziness. The fistula was limited to the lateral semicircular canal in 83 cases and involved the labyrinth more extensively in 14 instances. The intact canal wall technique was used in less than 60% and an open cavity technique in 25% of the cases. Severe or total sensorineural hearing impairment developed postoperatively in 8% of the lateral canal cases and in over half of the extensive fistula cases. Five percent had incapacitating dizziness for up to six months postoperatively. When a labyrinthine fistula is encountered in an only hearing ear we usually recommend a classical modified radical mastoidectomy. In other instances the procedure performed will vary with the status of the opposite ear, the extent of the fistula, the sensorineural function of the involved ear and the size of the mastoid.


The ultrastructure of the endolymphatic sac in Ménière's disease.

Meniere's disease is a well recognized clinical entity, yet the etiology and pathophysiology of the disease is not fully understood. Impaired endolymphatic sac function resulting in faulty reabsorption of endolymph has been implicated in the production of the disease. The histopathological findings from biopsied sac specimens and observed by transmission (TEM) and scanning (SEM) electronmicroscopy in two patients with early Meniere's disease are presented and discussed. Extensive subepithelial fibrosis with loss of vascularity and obliteration of portions of the lumen of the endolymphatic sac by an ingrowth of collagen is noted in both specimens. The implications of these findings are discussed and the need for more TEM and SEM studies of inner ear disorders is stressed.


New patterns in genetic and congenital otonephropathies.

In a series of chronic renal and congenitally deaf patients 24 were identified as having inborn renal and otologic disease. Sixteen patients, representing 14 families, had genetic disorders. Only two had the features of Alport's syndrome. The patients were classified as follows: 1) Probable Alport's--2 patients (1 family); 2) Atypical hereditary nephritis and sensorineural hearing loss--7 patients; 3) Renal and inner ear anomalies--1 patient; 4) Renal, inner ear and multiple anomalies--4 patients. The temporal bone pathology in one case showed primary neural atrophy and a mild Mondini malformation. In another a Scheibe defect and unusual calcific structures were found in the cochlear duct. 5) Renal, external or middle ear and multiple anomalies--6 patients (5 families); 6 Renal, middle and inner ear anomalies and multiple anomalies--2 patients. A temporal bone obtained from one case showed combined middle and inner ear defects. In the other, who had a chromosome defect, predominantly middle ear anomalies were found. 7) Nephrotic syndrome and congenital hearing loss--1 patient; 8) Unclassified--1 patient. Some cases represent entities apparently not previously described. Probably most interesting is the delineation of hereditary nephritis and deafness distinct from Alport's disease.


Hearing results following atticotomy.

Transmeatal atticotomy, a common otosurgical procedure near the turn of the century, has since enjoyed only sporadic periods of popularity. An earlier report illustrated the efficacy of the atticotomy operation in ablating cholesteatoma in 83% of cases. However, the ossicular chain usually suffers discontinuity either through erosion by cholesteatoma or surgical disarticulation. In ears with an intact chain, the incudostapedial joint is usually separated to avoid injury that may be transmitted to the inner ear if the rotating burr contacts the ossicles. The purpose of this paper is to portray the types of hearing restoration attempted and the results achieved in 55 patients who had an atticotomy procedure and had been followed for six months to eight years. The number of patients who attained serviceable hearing are compared to those that did not, with regard to such factors as the hearing level and state of the ossicles preoperatively as well as the extent of the surgery required for removal of the disease. The hearing results in these patients who underwent atticotomy compare favorably to those cited in the literature for tympanoplasties done with the modified radical mastoidectomy or the intact canal wall tympanomastoidectomy.


Surgical management of petrous apex meningioma.

When centered in the petrous apex, meningiomas behave like other neoplasms occuring in that region. The petrous apex can be approached by several routes: posterior craniectomy; middle fossa craniectomy; translabyrinthine, transcochlear, and transethmoidosphenoid approaches. A patient harboring a malignant meningioma in her petrous apex is presented. A middle fossa craniectomy, coupled with posterior displacement of the facial nerve, allowed access to the entire temporal bone from above. The patient received postoperative irradiation.


Brain radiation necrosis following treatment of an esthesioneuroblastoma (olfactory neurocytoma).

Esthesioneuroblastoma is an uncommon malignant nasal tumor which may be difficult to diagnose. Once diagnosed, selection of treatment may be a dilemma. Some advocate preoperative radiation and surgery; others, surgery and postoperative radiation if needed. A case that developed brain necrosis from postoperative radiation is presented. It is felt that the possibility exists that the patient might still be living with tumor had irradiation not been given. This is a plea for the conservative approach to treatment. The author agrees with John S. Lewis that it is unwise to use all modalities at once as there is no definite evidence that any one method of treatment or a combination of surgery and irradiation will alter the prognosis. The paper stresses the brain hazards of irradiation.


The ultrastructural diagnosis of tumors of the head and neck.

Electron microscopy has proved to be a valuable diagnostic tool in surgical pathology. As shown in three illustrative cases, the procedure is most useful in accurately classifying light microscopically diagnosed undifferentiated tumors of the head and neck, and is also helpful in predicting the origin of cervical lymph node metastasis in occult cancer. It also serves to quality control diagnoses made by light microscopy. All surgical specimens are fixed in a fixative that gives adequate ultrastuctural preservation and allows retrieval and examination by electron microscopy, if indicated. Recent technical improvements have resulted in a turn-around time of less than two days, thus making diagnostic electron microscopy clinically useful. The ultrastructural examination of undifferentiated tumors has a high diagnostic yield, often obviating additional diagnostic procedures and exploratory surgery. The correct diagnosis results in appropriate therapy and accurate assessment of prognosis.


Treatment of spastic dysphonia by recurrent laryngeal nerve section.

The problem of management of patients with spastic dysphonia has been complicated by a general resistance to speech therapy, psychotherapy, hypnotherapy, and drug therapy. Dedo introduced the concept of recurrent laryngeal nerve section in an attempt to eliminate the hyperfunction and excessive adduction of the vocal folds. Eleven patients were treated by RLN section with satisfactory results in 8 and some improvement in the other 3. The operation was found to be generally uncomplicated and required on average 4 days of hospitalization. Dedo's theory that spastic dysphonia is caused by a neurotropic viral-induced proprioceptive nerve deficit represents a new search for organic cause. His most recent report of finding unmyelinated fibres in one-third of the resected recurrent laryngeal nerves is of questionable significance. The evidence of deep emotional conflict and/or compulsive life-style is found in the majority of the patients, but the syndrome is not typical of an hysterical or conversion neurosis. Regardless of etiologic theory, RLN section is an effective treatment in selected, long-standing, and resistant instances of spastic dysphonia.


Prevention of major and minor fistulae after laryngectomy.

Every Head and Neck surgeon has special techniques which he uses to get maximum rates of five-year survival and minimum fistula formation, especially major fistula and carotid rupture. The literature reflects a wide variation in the rate of fistula formation. We reviewed the senior author's prior 78 total laryngectomies and noted a fistula rate of 10.3% (6.4% minor fistulae and 3.9% major fistulae). We also reviewed contributing factors and discuss surgical techniques designed to minimize fistula formation.


A retrospective study of traumatic tympanic membrane perforations in a clinical practice.

A retrospective study of 227 traumatic tympanic membrane perforations was made. These perforations were treated in a clinical practice of otolaryngology between January 1969 and July 1977. The following conclusions were supported by the data obtained: 1. Larger perforations are less likely to heal spontaneously. 2. Lightning and molten metal injuries are less likely to heal spontaneously. 3. Final healing and hearing results are good regardless of the mode of therapy employed. 4. Spontaneous healing gives better results than early surgical intervention. 5. Infection adversely affects healing in traumatic perforations. Based on information delineated in the paper, a logical plan of treatment for traumatic perforations is presented.


Medullary carcinoma of the thyroid as a laryngeal problem.

A neuroendocrine secreting tumor, initially presenting as a laryngeal problem, is reported. Subglottic biopsy, first interpreted as paraganglioma, was finally diagnosed as medullary carcinoma of the thyroid. The complex testing required to arrive at an accurate diagnosis of this uncommon thyroid malignancy is discussed. The sparse occurrence of the neoplasm in the laryngologic field, as well as the necessity for differentiating it from other neuroendocrine tumors, bear consideration.


Clinical trial of diaminodiphenylsulfone (DDS) in nasal and nasopharyngeal rhinosporidiosis.

Rhinosporidiosis is a fairly common problem for the Otolaryngologist in many parts of the world, because of its prompt recurrence after surgical excision. Though not a fatal disease, it inflicts various kinds of social and economic strain on the patients and their families. No medical treatment has been found to be effective in controlling rhinosporidiosis. Such drugs as griseofulvin and amphotericin have been tried without much benefit. In this clinical trial with dapsone on 32 patients (71.4%) did not have recurrence in a three year period and none of them needed surgery in that period. Thirty-two patients were used as controls, and 93% of them needed surgery for recurrent rhinosporidiosis in the same three year period. Dapsone (diaminodiphenylsulfone) is a relatively safe drug to use, and no major side effects were noticed in this trial.


Dermoid cysts of the floor of the mouth and lateral neck.

Dermoid cysts of the floor of the mouth and submandibular area represent an unusual clinical entity. We present three such cases and review their clinical presentation and pathologic classification. This study stresses the importance of recognizing and excising any tract leading from such cysts to the midline mandible or hyoid, in order to avoid a recurrence, since these tracts may be epithelialized.


The effect of static tympanic pressure gradients on hearing sensitivity in normal subjects.

The effects of static tympanic air pressure gradients on hearing sensitivity was studied by introducing overpressures of 100 mm H2O to 400 mm H2O into the ear canals of 22 normal subjects. Sweep frequency threshold measures were obtained using a pressure-tight probe transducer driven by a Bekesy automatic audiometer. These gradients of tympanic pressure disequilibrium produced threshold losses through 4000 Hz, most prominently for the region of 500 to 1000 Hz, that increased systematically with the degree of overpressure. The data may be useful in estimating the degree of conductive loss associated with middle ears presenting retraction without effusion and normally compliant though negatively skewed tympanograms.


The screening value of monothermal caloric tests.

A valid screening caloric test should decrease examination time, increase patient comfort and maintain a high degree of sensitivity in predicting bithermal (BT) caloric results. This prospective study of 362 consecutive electronystagmograms (ENG) compared right/left (R/L) difference results obtained using monothermal (MT) warm and cold irrigations alone with that of the (combined) BT tests. Comparing MT warm and cold irrigations, false negative (normal MT but abnormal BT test) results were obtained in 14% and 25% of irrigations, while false positive (abnormal MT but normal BT test) information was obtained in 22% and 15% of irrigations, respectively. False negative MT tests preclude detection of the abnormal BT test, while false positive tests require unnecessary completion of the BT caloric irrigations. This lack of diagnostic sensitivity limits the usefulness of the MT irrigation as a screening test.


Lipogenesis in the developing brain: utilization of radioactive leucine, isoleucine, octanoic acid and beta-hydroxybutyric acid.

Incorporation of radioactivity from intracranially injected radioactive leucine, isoleucine (ketogenic amino acids), octanoic acid and beta-hydroxybutyric acid into the brain lipids of 15 to 16 day-old rats was examined. The results showed that radioactivity from all the above precursors was incorporated into brain lipids. Radioactivity from injected isoleucine was incorporated into odd numbered fatty acids indicating an alternate pathway to alpha-oxidation for the biosynthesis of these fatty acids in the brain. For some as yet unclear reasons, a substantial portion of the radioactivity from injected octanoic acid was incorporated into free fatty acids. Utilization of these compounds for providing carbon for lipogenesis during development under unstressed normal conditions is discussed.


Occurrence of plant sterols in aquatic vertebrates.

Plant sterols were found by gas liquid chromatography in the sterols of five species of aquatic vertebrates; mackerel (Scomber japonicus), rainbow trout (Salmo gairdnerii), smelt (Osmerus dentex), sardine (Sardinops melanosticta) and chimera (Chimera phantasma). The sterols of chimera liver, sardine flesh and sardine viscera contained 9.0, 2.4 and 3.1% of C28 and C29 sterols in addition to 86.7, 96.6 and 95.2% of cholesterol. The occurrence of norcholestandienol, campesterol, beta-sitosterol and C28 stanol was shown by combined gas chromatography-mass spectrometry. Sperm whale (Physeter catodon) sterols consisted of more than 99% cholesterol with only traces of 22-dehydrocholesterol.


A comparison of the ganglioside distributions of fat tissues in various animals by two-dimensional thin layer chromatography.

The ganglioside distributions of various fat tissues from human, rabbit, rat, mouse, chicken and frog were compared with pig adipose gangliosides by two-dimensional thin layer chromatography. It was found that there is a remarkable species variation in ganglioside distribution, especially in the composition and relative concentration of complex gangliosides. Differing from pig adipose tissues, those of human, rabbit, rat, mouse, chicken, but not frog, contained GM3 as a most abundant ganglioside. The data for human, rabbit and chicken indicated a simple distribution of only NeuAc-type gangliosides, while those for rat and mouse indicated a rather complicated pattern containing both NeuAc- and NeuGc-type gangliosides. The ganglioside pattern of the frog fat body differed markedly from those of mammalian fat tissues because of the presence of three different, unusual monosialosylgangliosides as major components. In other respects, a substantial amount of disialosylgangliosides was commonly found in all animal fat tissues.


Effect of marine oil and rapeseed oil on composition of fatty acids in lipoprotein triacylglycerols from rat blood plasma and liver perfusate.

The fatty acid patterns of triacylglycerols (TG) from very low density lipoprotein (VLDL) in blood plasma and liver-perfusate from rats fed partially hydrogenated marine oil or rapeseed oil were determined. In the plasma from rats fed rapeseed oil for three days and three weeks, there was a small but significant decrease in the percentage of 22:1 fatty acid from 17.2 to 11.2% with length of feeding. In liver-perfusate, the comparable decrease with dietary rapeseed oil was from 18.5 to 5.2%, and with dietary marine oil from 13.4 to 8.0%. In contrast to the liver-perfusate, the remaining liver had only a very low 22:1 composition (ca 2%) independent of feeding period or diet. The results indicated that the liver exported the very long chain fatty acids and that an adaptation took place after three days feeding with rapeseed oil or marine oil. This adaptation in the liver could possibly explain why TG accumulation in hearts, which appears after three days' feeding with rapeseed oil or marine oil, disappears after an extended feeding period.


Isolated brain capillary endothelia: influence of various levels of essential fatty acids on the acyl group composition of glycerophospholipids.

On day seven of gestation. Wistar rats were assigned to a high essential fatty acid (EFA), low EFA, or a fat free diet. The same diets were continued during lactation. On weaning, the offspring were fed the same diets as their mother. Rats were killed at 222 days, brain capillary endothelia isolated, and total lipids extracted from the purified capillaries. The composition of the constituent fatty acids of ethanolamine glycerophospholipid (EGP), choline glycerophospholipid (CGP), and the alk-1-enyl EGP composition from each diet is reported. A decrease in dietary EFA led to reduced proportions of total saturated acyl groups in EGP with no change observed in the total saturated acyl groups from CGP, and an increase in monoenoic fatty acids, particularly 18:1n-9 for each phospholipid class. The proportions of 20:4n-6 in alk-1-enyl EGP were reduced in fat-free fed animals. In addition, the relationship between 20:3n-9 and 20:4n-6 fatty acids in brain capillary endothelia were markedly increased with a reduction in dietary fat. Low EFA and fat deficient animals showed a tendency to sequester 22:6n-3.


1,25-Dihydroxyvitamin D3 increases the activity of the intestinal phosphatidylcholine deacylation-reacylation cycle.

The activity of the intestinal phosphatidylcholine deacylation-reacylation cycle has been found to be stimulated by 1,25-dihydroxy-vitamin D3. The stimulation of this cycle thus provides a possible mechanism for the reported retailoring of the fatty acid composition of phosphatidylcholine in intestinal cell membranes by 1,25-dihydroxy-vitamin D3 and its analogue, 1alpha-hydroxyvitamin D3.


The importance of the steric configuration of lysophosphatidylcholine in the lymphatic transport of fat.

The importance of the steric configuration of lysophosphatidylcholine in the lymphatic transport of fat was investigated in bile fistula rats. It was found that the feeding of 1-palmitoyl-sn-glycero-3-phosphocholine increased the lymphatic output of phosphatidyl choline and triacylglycerol, while the feeding of 3-palmitoyl-sn-glycero-1-phosphocholine had no effect. In intestinal microsomes of the bile fistula rats, it was found that the lysophosphatidylcholine acyltransferase was stereospecific in acylating the 1-acyl-sn-glycero-3-phosphocholine enantiomer. The significance of these findings is briefly discussed.


Isolation and partial characterization of the neutral glycosphingolipids and gangliosides of the human heart.

The glycosphingolipids (GSL) of the human heart muscle have been isolated from total lipids by column and thin layer chromatography and their sugars and fatty acids analyzed by gas liquid chromatography. Hearts from traffic victims were obtained at autopsy between 12 and 16 hr after death and dissected into parts (left and right ventricular walls, intraventricular septum and papillary muscle). The neutral GSL content for those parts of the hearts of two males aged 22 and one female aged 14 ranged from about 90 to 160 nmoles/g wet weight. Trihexosyl ceramide and globoside were the most abundant neutral GSL. Total ganglioside content was about 50 nmoles/g wet weight, and the most abundant gangliosides were partially characterized as GM3 and GM1; other mono-, di- and trisialogangliosides were also present. Differences in the content and composition of neutral GSL and gangliosides between the heart and other human tissues are discussed. It is concluded that the patterns of these two GSL fractions of the heart are more complex than those of the extraneural human tissues.


Leucine as an in vitro precursor to lipids in rat sciatic nerve.

The in vitro incorporation of lucine, isoleucine and pyruvate into lipids was compared and the possibility that leucine might serve as an in situ precursor to the corresponding iso fatty acids in the rat sciatic nerve was studied. The relative incorporation of 14C from leucine into lipids vs. nonlipids was 20%, and the incorporation of label into total lipids from leucine was one-halp that from pyruvate. The incorporation of label from leucine and pyruvate into sterols was nearly equivalent, but the incorporation of label into all other lipid classes from leucine was less than that from pyruvate, and the incorporation of label from isoleucine into lipids was much less in all cases. No detectable label from leucine was incorporated into brached chain fatty acids. It is concluded that leucine may be a substantial in vitro precursor to all major lipids in peripheral nerve, espeically sterols. The possibility and significance of a leucine catabolic pathway in the cytosol in relation to availability of 3-hydroxy-3-methylglutaryl CoA for sterol biosynthesis is discussed.


Fatty acid positional specificity in phospholipids of L1210 leukemia and normal mouse lymphocytes.

The positional distribution of fatty acids in the choline and ethanolamine phosphoglycerides of the L1210 murine leukemia cells was determined and compared to that of normal mouse lymphocytes. The major phospholipids of both cell types had appreciable degrees of positional specificity as evident from the higher percentage of saturated fatty acids in position 1 and of polyunsaturated fatty acids in position 2. The L1210 cells had less arachidonate and more linoleate in position 2 of choline and ethanolamine phosphoglycerides as compared to the normal lymphocytes. However, there were similar proportions of saturated, monoenoic and polyenoic fatty acids in positions 1 and 2 of the phospholipids of the L1210 leukemia cells and the lymphocytes, These data demonstrate that fatty acid positional specificity is retained in the major phospholipids of this rapidly growing tumor.


Composition of lipids bound to pure cytochrome P-450 of cholesterol side-chain cleavage enzyme from bovine adrenocortical mitochondria.

Phospholipids bound to highly purified cytochrome P-450 from bovine adrenocortical mitochondria, part of the enzyme complex responsible for catalyzing the conversion of cholesterol to pregnenolone, have been examined for comparison with the bulk phospholipids of the mitochondria from the same tissue. In both cases, the major phospholipids are phosphatidylcholine (PC) (37%) and phosphatidylethanolamine (PE) (56%), as well as smaller amounts of sphingomyelin and diphosphatidylglycerol. The fatty acid compositions of the four classes of phospholipids and of the neutral lipids bound to the pure enzyme are indistinguishable from those of the respective mitochondrial lipids. They are also similar to those of mitochondria from other organs except for high levels of arachidonate and low levels of diphosphatidylglycerol.


The metabolism of dihomo-gamma-linolenic acid in man.

Orally administered dihomo-gamma-linolenic acid (DHLA) is well absorbed in man; it appears in blood after ca. 4 hr first as triglyceride ester and later as phospholipid. After sustained-dosing, DHLA penetrated membrane pools and all phospholipid components but, depending on the dosage, reached a metabolic equilibrium in 4-16 days. Intact platelets do not accumulate arachidonate following DHLA administration, and species differences occur in the capacity of animals to metabolize DHLA to arachidonic acid (AA). The rat appears to be unusual in having a very active hepatic delta5-desaturase enzyme system. Potentially antithrombotic changes in platelet function which followed the administration of DHLA to man were accompanied by a significant increase in the capacity of platelets to synthesize PGE1. Concomitant increases in PGE2 synthesis do not apparently result from an  increased production of AA and suggest that DHLA, or a DHLA metabolite, interferes with the metabolism of AA. Effects on thromboxane and prostacyclin synthesis are being studied.


The relationship of dietary fats to prostaglandin biosynthesis.

The direct and indirect evidence that the fatty acid composition of dietary fat is involved in the regulation of prostaglandin biosynthesis was reviewed. Direct evidence included effects of essential fatty acid deficiencies and excesses on endogenous tissue levels and production rates of prostaglandins by several tissues. Indirect evidence included lipolytic, platelet aggregatory, hypertensive, inflammatory and immune responses. In general, composition of dietary fat did not affect prostaglandin biosynthesis unless a biochemical essential fatty acid deficiency was induced or the linoleate to saturated fatty acids ratio of the dietary fat was greater than 5. Most results were interpreted in light of changing fatty acid composition; however, very few direct measurements have been made.