Characteristics of optic nerve innervation in the rat superior colliculus as revealed by field potential analysis. With lightly anesthetized rats, field responses to single optic nerve (ON) and optic chiasm shocks were studied in superficial layers of the superior colliculus, i.e., St. zonale (SZ), St. griseum superficiale (SGS) and St. opticum (SO). Based upon characteristics in the depth profile of the field response within the superficial layers, we identified three zones of N3, N2, and N1 from the SZ in this order. The narrow N2-zone was localized around the middle part of the SGS and less distinct than the other two zones. The N3-zone was characterized by a N3-wave and the N1-zone with N1- and P3-waves. N3- and P3-waves were activated by slowly conducting ON fibers (5.0 +/- 1.4 and 4.2 +/- 0.6 m/sec, respectively) while the N1-wave was by fastest conducting fibers (16.3 +/- 4.1 m/sec). According to recent Golgi studies, hypothetical mechanisms underlying the three waves were proposed: the N3-wave was ascribed to the activities of small vertical fusiform cells in the SZ or the upper half of SGS, the N1-wave to those of narrow field vertical cells which predominate in the lower half of SGS, and the P3-wave to those of wide field vertical cells whose somata are in the lower half of SGS or in the SO. The N3-, N1-, and P3-waves were found to differ from each other in recovery function tested with double ON shocks as well as in the topographical analysis of amplitudes through a whole extent of the colliculus. The three systems represented by the three waves were suggested to play different roles in visual information processing within the superficial strata.


A four group classification of the rat superior collicular cells responding to optic nerve stimulation. With lightly anesthetized rats, activities of single cells responding to single optic nerve (ON) shocks were recorded from the superficial layers of the superior colliculus, i.e., St. zonale(SZ), St. griseum superficiale (SGS) and St. opticum (SO). According to response latencies and recording depths, four classes of cells were identified: I-, II-, III-, and IV-cells. Class I cells, recorded in the SZ or the upper half of SGS, were innervated by slowly conducting ON fibers of velocities slower than 4 m/sec. Class II cells, recorded from the middle part of the SGS, were innervated by ON fibers of intermediate velocity (4--8 m/sec). Class III cells, recorded from the lower half of SGS or the upper part of SO, were innervated by fast conducting ON fibers (faster than 8 m/sec). Class IV cells were recorded from the depth similar to the class III but they were innervated by slowly conducting fibers (4-1.7 m/sec). Class I cells revealed a long-lasting inhibition after initial excitation, being a sharp contrast with cells of classes II and III which were almost free from inhibition. Inhibition exerted upon class IV cells were of intermediate strength. Possible anatomical correlates of the four classes of cells and hypothetical modes of their ON innervation were discussed.


Visual receptive-field properties of single cells in the rat superior colliculus. Receptive-field properties were studied in single cells in the visual layer of the albino rat's superior colliculus. All the samples (N = 195) were identified as one of the four classes (I-, II-, III- and IV-cells) which were established previously on the bases of the response properties to single shocks to the optic pathway and of the recording sites. The four classes were located more deeply in the superior colliculus roughly in the order of from I to IV. Response latencies to single shocks to the optic chiasm were shortest in the III-cells, intermediate in the II-cells and longest in the I- and IV-cells. These cell classes turned out to be different from each other in a number of visual properties. 1) Receptive-field centers in the I- and II-cells (N = 26 and 27, respectively) were of either the ON-OFF or the ON type. Of class III (N = 47), one subgroup (IIIa) consisted mostly of the OFF type whereas the other (IIb) was made up mostly of the ON-OFF type. About two-thirds of the IV-cells (71/95) were of either the ON, the OFF or the ON-OFF type; except for two cells, the rest were all of the moving-sensitive type. 2) The average size of the receptive-field center was small (5.4 degrees +/- 2.3 degrees) in the class I, intermediate in the classes II and III (8.1 degrees +/- 2.1 degrees and 7.1 degrees +/- 2.7 degrees, respectively) and large in the class IV (18.1 degrees +/- 15.9). 3) Responsiveness to moving light stimuli (speeds, 40 degrees--90 degrees/sec) decreased in the order of IIIa, II and IIIb, and I and IV. 4) Maintained activity was lower in the superficially located cells (I, II and IIIa) than in the deeply located ones (IIIb and IV).


[State of the "contraction-relaxation" mechanism and the bioelectric activity of the myocardium in acute arterial occlusion]. The results of 57 experiments on adult mongrel dogs are shown. Acute occlusion of the terminal aorta was reproduced by means of a balloon catheter. The pressure in the cavity of the left ventricle and in the office of the aorta and the ECG were recorded synchronously. The load experienced by the heart grew by the 6th hour of occlusion of the terminal aorta. This is attended by disorders in excitability and trophics of the myocardium and inhibition of the rate of myocardial contractions. At the same time the potency of the system of myocardial relaxation grows. By the 12th hour of occlusion of the terminal aorta, not only are the myocardial contractility and bioelectric activity impaired, but the capacity of the myocardial relaxation mechanism diminishes. The restoration of the circulation in the involved extremities is attended with further inhibition of the main functions of the heart. A new index of the functional condition of the myocardium, the restoration index, is proposed.


[Effect of obsidan on the cardiovascular system under conditions of high-altitude hypoxia]. The effect of beta-adrenergic block on the circulatory reactions of a human being induced by high altitude hypoxia was studied by multi-channel rheography and indirect determination of systolic pulmonary arterial pressure. In healthy people not subjected to a pharmacological effect, 25-day stay at an altitude of 3,200 m was marked by an increase in cerebral blood flow at the beginning of adaptation and the development of pulmonary hypertension the maximum signs of which were recorded during the first days in the mountains. Daily intake of 80 mg of obsidan begun 3 days before the ascent levelled out the adaptative increase in cerebral perfusion and intensified the marked character and stability of hypoxic pulmonary vasoconstriction. It is concluded that great care should be exercised in giving obsidan at high altitude to individuals with even latent forms of right ventricular pathology since under conditions of hypobaric hypoxia beta-adrenergic block increases the load suffered by the right ventricular myocardium.


[Effect of high-altitude hypoxia on the course of experimental mitral heart defect]. The course of dosed insufficiency of the mitral valve in animals under lowland conditions is characterized by marked compensatory capacity of the organism. Under the effect of high-altitude hypoxia (3,200 m), the disease of the mitral valve is attended with overloading of the left atrium with the volume of blood and leads to acute hypertension of the pulmonary artery with subsequent decompensation of the right heart. In animals with mitral valvular disease under conditions of high altitude, strophanthin K produces a sufficiently complete cardiotonic effect which prevents weakening of the myocardial contractions, particularly in the early period of the defect in the mitral valve.


[Circulatory insufficiency and edema in experimental constriction of the thoracic segment of the vena cava inferior]. A method for reproducing circulatory insufficiency in rats by constriction of the intra thoracic portion of vena cava inferior is described. A sham operation on the control animals was restricted to thoracotomy. Rats which had been subjected to constriction of the vena cava consumed 0.85% sodium chloride solution intensively under conditions of free choice. This lead to rapid increase in mass with the development of subcutaneous edema, hydrothorax, and ascites within two to three days after the operation. Thinned out muscle fibres with decreased SDH activity were found in the myocardium of the both ventricles. Study of THO, 22Na, 36Cl, and thiocyanate distribution spaces showed that the total body water increase was consequent upon growth of the extracellular space with a constant intracellular volume.


[Role of electric stimulation of the heart during selective contrast examination of the coronary arteries with the use of the data of continuous recording of the bundle of His potentials and arterial pressure]. The frequency of disorders of the cardiac rhythm during injection of a contrast medium into the coronary vessel under different conditions was studied in 214 patients. Atropine premedication was applied as a preventive factor in 142 patients, atrial stimulation in 60, and both factors simultaneously in 12. In 10 patients a single injection of the contrast medium was performed without preventive measures. In 20 patients the changes were studied by recording the potentials of the bundle of His and the arterial pressure. On the basis of the bundle of His ECG data it is concluded that atropine and atrial stimulation produce an effect on individual links of the complex mechanism underlying the effect of the contrast medium on the cardiac conduction system.


[Retrospective evaluation of the pre-infarct period]. It is shown on the basis of retrospective appraisal of the course of ischemic heart disease in 235 patients hospitalized for acute macrofocal myocardial infarction that 78% of them had a prodromal period. The prodromal symptoms corresponded to those registered by WHO as preinfarction state. It was also shown that stable ischemic changes in the ECG during dynamic examination are of vital importance in the diagnosis of a preinfarction state. Problems of the medical tactics employed in the prodromal period of acute myocardial infarction are discussed.


[Characteristics of the indicators of the blood coagulation and fibrinolysis systems in the pre-clinical stage of ischemic heart disease]. Signs of dysfunction of the coagulation system and fibrinolysis were determined in 45 healthy young individuals who had such risk factors in relation to ischemic heart disease as arterial hypertension, hypercholesterolemia, smoking, aggravated heredity, permanent emotional overstress, etc. These signs were manifested by a tendency to augmentation of blood coagulation and compensatory activation of fibrinolysis. Ischemic-type changes were detected on the ECG after a physical load. It is assumed that dysfunction of the coagulation system and fibrinolysis is an additional risk factor in relation to ischemic heart disease, while derangement of compensatory fibrinolysis tension with the subsequent tension of its components may lead to the development of coronary thrombosis.


[Effect of the type of work on the development of coronary arteriosclerosis]. The aorta and coronary arteries taken from 4,000 cadavers were studied by the visual-planimetric method. Atherosclerotic changes (fibrous patches, complicated lesions, calcinosis, stenosis of the coronary vessels) were significantly more frequent and more severe in individuals who had been concerned with mental work, males in particular, than in those who had performed physical work. This regular feature was less distinct among countrypeople, females in particular. It is concluded from thorough additional analysis of morphological material that the coronary atherosclerosis risk factor is not only the character of work but its intensity too, especially in individuals engaged in mental work for a lengthy period of time.


[Characteristics of central and regional hemodynamics in certain variants of the course of myocardial infarct]. In 96 patients with myocardial infarction the indices of central hemodynamics were studied by radiocardiography and the indices of regional circulation in the brain, lungs, liver, and distal parts of the extremity by rheoplethysmography. Peculiarities of regional and central hemodynamics depending on the clinical picture were revealed and the dynamics of the indices being studied were followed from the first to the 40th day of the disease. The authors discuss the mechanisms of the hemodynamic disorders and express their opinion on the expediency of the appropriate approaches to the treatment of patients depending on the hemodynamic changes revealed.


[Comparison of the data of the veloergometric test and coronarography in ischemic heart disease]. The results of the bicycle ergometry test were compared with the findings of coronarography in 254 patients with ischemic heart disease or suspicion of it. The high diagnostic significance of the test was demonstrated; stenosis of the heart coronary arteries was found in 73% of patients producing a positive test. The occurrence of an attack of angina pectoris with simultaneous "ischemia" reduction of the ST segment by 1 mm and more is a significant sing of a positive test. The severity of changes in the coronary arteries grows when these signs are combined with poor tolerance of physical load. With the higher degree of stenosis and an increase in the number of involved arteries load tolerance decreases, while the percentage of positive results of the load test increases.


[Electrocardiography in women with angina pectoris during physical exertion]. Comparative study was conducted of ECG changes during an attack of angina pectoris induced by physical exertion on a bicycle ergometer in 74 females and 100 males suffering from angina pectoris. It is shown that with a similar clinically determined severity of angina pectoris, tolerance to physical exertion is significantly lower in females than in males. Essential differences were also revealed in the ECG changes during an anginose attack. The data obtained are evidence that the approach to the appraisal of the results of load tests in ischemic disease of the heart in females should evidently differ from that in males.


[Informative value of the indicators obtained during catheterization and ventriculography of the left heart ventricle]. It is found that the main indices determined in catheterization and ventriculography of the left ventricle still provide insufficient information. This is displayed by their considerable variations under normal conditions (conventional normal values). The functional left ventricular volumes vary least in adults; the ejection fraction is most informative. Contraction of the longitudinal axis of the left ventricle and of its transverse diameters and the circular rate of myocardial contraction are most variable. It is necessary to generalize a great scope of material to obtain the normal sex and age values of all indices.


Malignancies of the urinary tract and their relation to analgesic abuse. A relationship between analgesic abuse and urothelial renal pelvic tumors was first observed in 1965. Since then more than 100 cases of such tumors have been reported in abusers of phenacetin-containing drugs; most of these cases have been from Sweden. Many patients had a preexisting nephropathy with renal papillary necrosis. The total consumption of the drugs could be estimated to several kilograms, and the average period of consumption was 17 yr in the Göteborg study. The manifest development of the tumor often came a few years after the cessation of the drug abuse. The clinical picture and the pathologic findings are described and the five-year survival rate is given. Multiple tumors in the urinary tract were common. Carcinogenic factors are discussed. Phenacetin is an aromatic amide with N-hydroxylated metabolites, closely related to known carcinogenic amines like the naphthylamines which earlier caused occupational bladder cancer. Furthermore, the data on exposition (consumption) time and tumor induction time were very similar in occupational bladder cancer and in renal pelvic cancer related to analgesic abuse. Animal experiments of long-term phenacetin feeding have produced a high degree of papillary epithelial hyperplasia. Further investigations are under way.


Changing concepts in pathogenesis and morphology of analgesic nephropathy as seen in Europe. A detailed analysis of 60 autopsy cases of AN is presented. Renal papillary necrosis is the hallmark of AN. Special emphasis is given to early changes in the basement membranes and the ground substance of the renal papilla observed by light and electron microscopy. The "interstitial nephritis" in the renal cortex is secondary to papillary changes. The histologic picture of the cotex is often complicated by bacterial infection and, therefore, is complex. An unusual hyalinization of small vessels beneath the urothelium of the mucosa of the urinary tract, similar to that seen in the inner medullary zone, has been called "analgesic microangiopathy". Its significance is not clear. The renal papillae, the mucosal membranes of the urinary tract, the liver, the cartilages, and the skin often display a striking brownish discoloration caused by a lipid-containing pigment. Statistical data from out autopsies in Switzerland show no decrease in death rates of AN. This is in contrast to reports from Denmark and Sweden where the sale of phenacetin has been restricted by prescription.


Pathology of analgesic nephropathy: Australian experience. Analgesic nephropathy was first studied in Switzerland and Scandinavia, and most observers thought that papillary necrosis, a feature of the pathology, was the result of chronic interstitial nephritis, the other principal feature. From 1962, reports indicated a high incidence of analgesic nephropathy in Australia and suggested that papillary changes preceded cortical damage. Later, associated uroepithelial carcinoma was noted. Early papillary lesions consist of necrosis of elements around groups of collecting ducts. Necrosis extends upward through the medulla from the papilla and gradually intensifies to total papillary destruction. Fat and calcium accumulation and changes in matrix mucopolysaccharide are markers of papillary injury. Cortical atrophy is dependent upon collecting duct obstruction and is proportional to the degree of obstruction. Infection may complicate late pathologic changes. It is suggested that in the early stages the disease represents an injury to "concentrating columns" in the medulla.


Epidemiological study in Switzerland.

Epidemiological study in Switzerland. A study group of originally 623 employed women of Northwestern Switzerland who were aged 30 to 49 yr and showing objective evidence of intake of phenacetin-containing analgesics, and a control group of 621 comparable women showing no such intake, were examined in 1968 and followed-up five times from 1969 to 1975 for laboratory evidence of urorenal disorders. Mortality was higher in the study group, with 21 deaths, compared to the control group, with 5 deaths, and was higher than expected in a comparative population in Switzerland (P less than or equal to 0.05). In both study and control groups, morbidity was low. There was no difference between the study and control groups with respect to subsequent proteinuria and hematuria. The seven-year incidence of low urine specific gravity after overnight thirsting was higher in the study group than in the control group (2.9% vs. 1.0%), and the incidence of raised serum creatinine was also significantly higher in the study group (2.9% vs. 0%). However, when the study group was further subdivided into a subgroup showing evidence of high intake of phenacetin-containing analgesics and one showing low-intake, only the high-intake subgroup had an incidence of raised serum creatinine concentrations (5.3%), significantly higher than the control group (0%), whereas the low-intake subgroup had an incidence (0.4%) similar to the control group. Also the high-intake subgroup showed significantly higher rates of bacteriuria than the controls (P less than or equal to 0.004).


Experimental renal papillary necrosis.

Experimental renal papillary necrosis. Review of experimental work indicates that renal papillary necrosis (RPN) is more readily induced by mixtures of analgesics which include phenacetin or paracetamol, than by either of the latter drugs alone. In an experiment in which moderate doses of analgesics were given to rats over a long period, it was shown that aspirin had a greater nephrotoxic effect than either phenacetin or paracetamol although less than in combination with either. In a study of the evolution of aspirin-induced damage, the earliest changes were shown to occur in the interstitial cells. There was also loss of medullary mucopolysaccharides. Occlusive lesions were demonstrated in the vasa recta. Using partial papillectomy, it was shown that the development of analgesic-induced cortical lesions did not depend on the presence of papillary necrosis. It was suggested that the early papillary changes might be due to ischemia, medullary blood flow being reduced as a result of aspirin's action as an inhibitor of prostagladin synthesis. The lesions in the vasa recta might cause ischemia at a late stage, leading to total RPN.


Genesis of analgesic nephropathy in the United Kingdom. Analgesic nephropathy is more common in Western Scotland than elsewhere in the United Kingdom. This appears to be a consequence of the frequency with which local people take Askit, a preparation different from most other British analgesics in that they contain more caffeine and in their presentation as powders. Surveys of different populations in Glasgow suggest that while aspirin and paracetamol tend to be taken relatively infrequently and for appropriate reasons such as pain, Askit is more likely to be taken with excessive frequency for its supposed mood-altering properties. Working-class women with psychiatric problems are especially prone to daily self-medication. Study of individuals with analgesic nephropathy reveals that in Western Scotland, at least, the cause is dependence on analgesics. The characteristics of this include a need to continue taking and to slowly increase the dose of analgesics, partly owing to tolerance and partly to treat symptoms the analgesic ingestion has caused, as well as a psychic dependence resulting from appreciation of the psychotropic effects of the compound analgesics. When compared with matched controls, those who develop the "analgesic abuse syndrome" are more likely to have a family history of analgesic abuse, alcoholism, and psychiatric disorder. They tend to be introverted and neurotic, are prone to abuse other drugs and many have had previous psychiatric treatment.


Radiological changes of renal papillary necrosis. The radiological changes of renal papillary necrosis are independent of its etiology. If total papillary necrosis (TPN) or partial papillary necrosis (PPN) is present, radiological findings are diagnostic. Whereas, if the necrotic papillae remain in situ (NIS) none of the typical radiologic features of papillary necrosis are seen. Serial radiologic studies are useful in renal papillary necrosis. Extension of papillary or medullary cavities, shrinkage of the kidney, and calcification thereby may be noted. Radiologic changes involving the ureter and bladder are those of complications such as ureteritis or development of a transitional cell carcinoma. The latter most often appears in the renal pelvis.


Renal response to phosphorus deprivation in the isolated rat kidney. In order to study further the adaptation of inorganic phsophate (Pi) reabsorption during phosphorus depletion, Pi transport was measured at three perfusate Pi concentrations in isolated perfused rat kidney preparations, utilizing synthetic albumin-containing cell-free perfusate. With elevation of the perfusate Pi, phosphaturia was significantly less, and absolute Pi reabsorption was significantly greater in kidneys derived from phosphorus-deprived rats than in organs from nondeprived counterparts. Prior parathyroidectomy did not affect the transport of Pi by the isolated kidney preparation. Increasing the perfusate Pi did not diminish hypercalciuria in kidneys from phosphorus-deprived rats. The results indicate that the adaptive response in Pi reabsorption during phosphorus deprivation can be demonstrated independently of the composition of fluid perfusing the kidney. The mechanism underlying the adaptation, however, remains unclarified.


Pre-eclampsia with the nephrotic syndrome. Heavy proteinuria and/or the nephrotic syndrome rarely occur late in pregnancy. We report the clinical and renal biopsy findings on 11 patients with the nephrotic syndrome occurring during pregnancy in whom light and electron microscopic findings were characteristic of pre-eclampsia. Immunofluorescent microscopy revealed deposits of IgG, IgM, IgA, beta 1C globulin, and fibrinogen, predominantly in the subendothelial position. Only two patients were primigravid; three were in their second or third pregnancy; in six, pre-eclampsia first occurred in the fourth to eighth pregnancy. Clinical abnormalities appeared first between the 23rd and 39th week of gestation. All patients had marked elevation of blood pressure and of serum uric acid levels. Of the 12 infants, eight were alive and well, including one set of twins; four were stillborn. Following delivery, clinical resolution was similar to that in less severe pre-eclampsia. The findings suggest the possible importance of the role of intravascular coagulation in the genesis of pre-eclampsia.


Micropuncture studies of the transport of individual amino acids by the Necturus proximal tubule. Absorption of amino acids by the necturus proximal tubules was measured under free-flow conditions The coexistence of proximal tubular amino acid influx was determined by infusing saline into tubular lumens by the stopped-flow microperfusion technique. Under free-flow conditions, fractional absorption of individual amino acids ranged from 0.30 +/- 0.18 (glutamic acid) to 0.96 +/- 0.02 (proline), with 14 of 19 values greater than 0.75. The transport avidity for a given amino acid bore no relationship to its molecular weight, transport class, or plasma concentration. The values obtained for tubular fluid/plasma (TF/P) were very comparable to those reported for the rat. In stopped-flow microperfusion experiments, samples of isotonic saline residing in tubule lumens for 20 min were found to contain all the amino acids present in plasma (filtrate). The concentrations of all except the acidic anionic pair, glutamic acid and aspartic acid, were remarkably similar to those obtained by collection of end proximal samples in free-flow studies. The very high concentrations of the acidic amino acids may reflect their passive distribution across the luminal cell membrane, active absorption having been impaired by the absence of some substance normally present in glomerular filtrate.


Renal micropuncture study of normotensive and Milan hypertensive rats before and after development of hypertension. Earlier studies of renal transplantation and of sodium metabolism indicated that the cause of high blood pressure in the Milan strain of genetically hypertensive rats (MHS) was altered renal function. To pinpoint the active factors, we used micropuncture to study several indices of renal function in normal (NR) and MHS rats at three different ages: A) 26 to 30 days, before development of hypertension (pre-MHS); B) 35 to 40 days; and C) 75 to 90 days, after the development of hypertension. The indices studied and the important differences found between the two strains were: 1) Single nephron filtration rate (SNFR) and late proximal tubular fluid delivery to the distal nephron (LPF). In group A, the pre-MHS rats had significantly lower values than did the NR (SNFR = 6.3 +/- 0.8 nl/min [MHS] vs. 8.3 +/- 1.2 [NR], P less than 0.01; LPF = 3.14 +/- 0.25 nl/min [MHS] vs. 4.1 +/- 0.35 [NR], p less than 0.05). In group C, the values in the MHS rats were significantly higher than those of the NR (SNFR = 17.3 +/- 1.4 nl/min [MHS] vs. 12.1 +/- 0.8 [NR], P less than 0.05; LPF - 7.4 +/- 0.5 nl/min [MHS] vs. 5.3 +/- 0.3 [NR], P less than 0.01). 2) Number of glomeruli. In group C only, the MHS rats had significantly fewer than did the NR rats (MHS = 55, 253 +/- 2,821 vs. NR = 64,527 +/- 2,900, P less than 0.05). 3) Glomerular filtration rate (GFR) and SNFR as a function of the mean blood pressure (MAP). In group A, the GFR of the MHS rats was lower than that of the NR rats (GFR = 0.38 +/- 0.03 ml/min . 100 g of body wt [MHS], 0.50 +/- 0.03 [NR] P less than 0.05). In group C, there was no longer any significant difference. At equal MAP, SNFR was equal in all the groups, except group A, where SNFR was significantly lower in MHS. 4) Pressure differences: Glomerular capillary pressure (gP). GP was significantly higher in MHS rats than in NR rats (group A, + 5.2 mm Hg; group C, + 6.7 mm Hg). In the pre-MHS rats, anesthesia significantly increased (P less than 0.001) the blood pressure difference between the two strains. This effect was not seen in the adult MHS rats. This may increase the differences in GP between pre-MHS and NR. 5) Afferent effective filtration pressure (EFPA). EFPA values were also higher in MHS rats (+ 2.9 mm Hg in group A, + 6.8 mm Hg in group C), but once again the effects of anesthesia probably account for the differences in magnitude seen between pre-MHS and NR. Only 22% of the absolute differences in systemic arterial pressure in the adult MHS and NR rats was transmitted to the glomerular capillary, while 33% of the difference was transmitted in the younger rats. These values suggest a reduced glomerular hydraulic conductivity, even though other explanations could not be excluded, and they are consistent with the hypothesis that the primary cause of development of hypertension in the MHS rats may be a decrease in SNFR.


Prolonged complement activation in mice. Because antibody responses to the alternative complement pathway activator, cobra venom factor, are T-dependent and B mice therefore do not develop resistance to its action, it was possible to examine whether renal injury occurs under circumstances of protracted third-phase alternative pathway activation. After periods of up to three months, no evidence from measurements of blood urea or proteinuria or from examinations with light microscopy immunofluorescence or electron microscopy was obtained to indicate a directly nephrotoxic effect of this type of complement activation.


Reduced renin activity in essential hypertension: a reappraisal. The apparent suppression of plasma renin activity in essential hypertensive patients compared to normotensive controls prompted an examination of factors which might be responsible for this difference in people taken from a blood pressure screening survey. Plasma renin activity was lower in 89 previously untreated "hypertensive" subjects than in an equal number of age- and sex-matched "controls" from the same community. The rise in plasma renin activity on standing or after frusemide was proportional to the resting level, and it was generally less in hypertensives, but small or absent responses were also seen in those with normal blood pressure. There was no evidence for a "low renin sub-group" among the hypertensives. Plasma renin activity fell with both increasing age and increasing arterial pressure. A low renin activity is more likely to be a consequence of hypertension than to be associated with its cause.


Hereditary polycystic kidney disease (adult form): a microdissection study of two cases at an early stage of the disease. Kidney fragments from two cases of hereditary polycystic kidney disease (adult form) at an early stage were examined by microdissection. Localized cystic cystic dilatations were found in proximal and distal tubules, loops of Henle, and collecting tubules. Entirely normal nephrons and collecting tubules were also observed. Abnormal branching of collecting tubules or the abnormal attachment of nephrons, as described in other microdissection studies, were not found. Our observations do not confirm the hypothesis that the adult form of hereditary polycystic kidney disease is the consequence of ampullary dysfunction during early development.


[Lactic acidosis--a possible complication in buformin-treated diabetics (author's transl)]. Lactic acidosis is defined as a state of metabolic acidosis (arterial pH below 7.36) due to an increase in the blood concentration of lactate above 2 mEq/l. Lactic acidosis may occur under a variety of conditions; the biguanide-induced lactic acidosis is due to the toxic effects of biguanides (buformin, metformin, phenformin). The clinical picture is characterized by the occurrence of disturbances of consciousness, severe acidosis with Kussmaul's respiration, shock, hypothermia and in about 30% of all cases hypoglycemia. Apart from the general principles of intensive medical care, therapy should comprise correction of the acid-base-disturbances and elimination of the offending biguanide. The efficacy of hemodialysis in the treatment of biguanide-induced lactic acidosis is difficult to evaluate. By a more sensible use of biguanides, lactic acidosis secondary to drug administration should become a rare event.


Differentiation between subtypes of primary hyperaldosteronism by multiple steroid measurement after dexamethasone administration. In 6 patients with primary hyperaldosteronism (P.H.) and a unilateral adrenal adenoma (A) and in 5 patients with P.H. obviously due to bilateral adrenal hyperplasia (H), multiple serum corticosteroids were measured after different dietary or drug regimens. After administration of dexamethasone on a normal sodium diet, serum levels of 11-deoxycorticosterone (DOC), corticosterone (B) and cortisol (F) were much lower in the H than in the A group. With respect to 11-deoxycorticosterone levels, there was no overlap between the two groups. Multiplication of individual serum DOC, B and F levels allowed a clearer separation of patients with A and H. This non-invasive method may offer an additional means in the differential diagnosis of P.H.


[Saralasin-induced changes of blood pressure, renin and aldosterone in essential and renal hypertension (author's transl)]. In 34 patients saralasin was infused after variable degrees of sodium depletion in order to differentiate between essential and renin-induced hypertension. After sodium-depletion of short duration mean arterial pressure dropped more than 10 mm Hg in 9 of 25 patients with essential and in 7 of 9 patients with renin-induced hypertension. After long-lasting sodium depletion the fall of mean arterial pressure exceeded 10 mm Hg in 11 of 16 patients with essential and in 8 of 9 patients with renin-induced hypertension. Thus saralasin did not discriminate essential and renin-induced hypertension. Also, plasma renin concentration before and after saralasin did not allow to differentiate between the two forms of hypertension. The changes of renin during infusion of saralasin was negatively correlated to the change of blood pressure. Renal vein renin ratio in patients with renovascular hypertension was not modified by saralasin. Renin and aldosterone changed inversely during saralasin infusion.


[Simultaneous comparative renal clearances and renal iodo (I125)-hippurate in man (author's transl)]. In 111 Patients with a wide range of renal function (normal to advanced renal failure) the renal clearances of Na-paraaminohippurate (CPAH) and of Na-orthojodohippurate--J125(COJ(J125(H) have been simultaneously determined under standardized clearance conditions. We found a significant correlation between the 2 parameters, defined by the equation CPAH = 1.11.COJ(J125)H. The scatter of the single observations however is considerable and hence the +/- 2Sy range is very large. The difference between the 2 clearances is not die to a competition at the same tubular carrier, since adding inactive carrier of OJH does not improve the ratio of the 2 clearances: CPAH = 1.13.COJ(J125)H. Rather the renal extraction of OJ(J125)H(EOJ(J125)H is considerably lower (74% than EPAH (90%). Our datas suggest that OJ(J125)H is not a suitable indicator to replace PAH for measurements of real renal plasma flow.


[Diagnostic significance of heat-induced inhibition of erythrocyte sedimentation (author's transl)]. Heat-induced inhibition of erythrocyte sedimentation (HIES) was examined in 158 cases. HIES is significantly lower in patients with a liver cell damage isolated or due to metastases of a neoplastic process in comparison to that in patients suffering from inflammation or malign tumor not involving the liver. Generally, HIES depends upon the concentration of lysophosphatidyl choline (lysolecithin) which is set free in plasma by lecithin-cholesterol-acyltransferase (LCAT) during incubation. In patients with lever cell damage, LCAT is diminished. HIES is being influenced by several factors: Lysophosphatidyl choline is bound to albumin, and this prevents its reaction on the erythrocyte surface. Lysophospholipase reduces the concentration of lysophosphatidyl choline in the plasma by splitting off its fatty acid in the alpha-position. Specific serum proteins, the so-called agglomerines, which are responsible for the acceleration of erythrocyte sedimentation, are counteracting the HIES. The concentration of albumin and agglomerines in plasma and the activity of lysophospholipase are subject to physiologically and pathologically caused deviations. Thereby, HIES is being influenced individually at varying degrees. This makes it difficult to estimate the LCAT activity which represents the principal cause of HIES. As a consequence, HIES seems not to be suitable for clinical diagnostics.


[Analysis of the hydroxyproline containing serum proteins in connective tissue diseases (author's transl)]. The serum proteins were fractionated on Sephadex G 200, their hydroxyproline content determined. Three protein peaks (I-III) containing different hydroxyproline concentrations could be separated. In connective tissue disorders accompanied by increased collagen synthesis or collagen degradation, an elevation of hydroxyproline was found in peak II. An increase of hydroxyproline always was associated with an increase of the serum proteins in the same fractions. Hydroxyproline serum levels above normal obviously are due to a certain capacity of the serum proteins binding free hydroxyproline and collagen metabolites.


[Detection of human proteins in the epoxy housing of implanted cardiac pacemakers (author's transl)]. On cardiac pacemakers with epoxy resin encapsulation of a certain type which had been implanted in humans for a considerable time, sessile human proteins were detected in the epoxy by means of immunofluorescence microscopy. These proteins are not extractable from shavings of the epoxy casing using the method described, as was shown by two different methods. The results of LOWRY's test on the eluate are invalid, because we assume that extractable amino groups are responsible for the positive results.


Tuberculin and dinitrochlorobenzene (DNCB) tests in cancer patients before and after cytostatic drug therapy. In 137 patients with different kinds of cancer and different cancer stage, cell-mediated immunity was investigated by DNCB (dinitrochlorobenzene) and tuberculin test. These two skin tests were performed before and after cytostatic drug combination therapy. For a collective of cancer patients we found a positive correlation between skin reactions and prognosis and a negative correlation between skin reactions and cancer stage. After cytostatic drug therapy skin reactions could be significantly stronger. This could be observed in 50% when one test was positive before chemotherapy and in only 20% when both tests were negative before chemotherapy. There existed a significant correlation between an increased reaction after cytostatic drug therapy and objective tumor regression. When skin reactions decreased, tumor progression was seen in all cases. Due to these observations we use skin reactions as a good parameter for therapy results. When delayed cutaneous hypersensitivity impairs 2--3 weeks after chemotherapy, we then change the cytostatic drug combination immediately. We cannot say at this moment, whether an improvement of cytostatic drug therapy can be reached in this way.


[On kinetics of the paraoxon hydrolysing enzyme in human serum (EC 3.1.1.2) (author's transl)]. Human serum contains an enzyme which hydrolyses Paraoxon (E-600, an organic ester of phosphoric acid) by splitting of p-nitrophenol. This enzyme is very specific and shows a statistically significant polymorphism: I.e. in a normal population there are three groups with high, middle and low enzyme activity. The results presented in this paper confirm this polymorphism by showing a differing kinetic behaviour of the enzyme in the three groups. Paraoxon, methyl-paraoxon and chlor-methyl-paraoxon are most likely hydrolysed by the same enzyme and in the same way. On the other hand hydrolysation of n-propyl-paraoxon seems to be dependent on a different enzyme. A kompetitive inhibition of paraoxon-hydrolysation is exerted by S-substituted analogues of paraoxon. Paraoxon-hydrolysation is not influenzed by the addition of singly or doubly desalcylized derivatives of Paraoxon or compounds in which the nitro group is not in the p-position.


[Biochemistry and clinical significance of oral exocrine pancreatic function test by means of fluoresceinedilaurate (author's transl)]. Column chromatography of extracts and secretions of the pancreas as well as of sera from patients suffering from inflammations of this organ yields three esterases different from each other in molecular size. These enzymes could be shown to be not identical with lipase. They may be classified as aryl-esterases considering their activities in hydrolyzing synthetic substrates such as esters of fluoresceine with fatty acids. Fluoresceinedilaurate, therefore, proved to be very advantageous in an orally performed test of exocrine pancreatic function. Healthy persons show in this procedure relative excretion of fluoresceine during ten hours of 66.3 +/- 30.4%, patients suffering from pancreatic diseases only 12.7 +/- 9.8% of the dye.


[Investigations on pituitary-testes axis in males with chronic liver diseases (author's transl)]. In 27 male patients (age 31--60 years) with chronic hepatic diseases--10 of which with alcohol-toxic cirrhosis (ACi), 10 with hepatitic cirrhosis (HCi) and 7 with chronic aggressive hepatitis (CHAH)--total testosterone (T) and total oestradiol-17 beta (E2) in plasma were determined before and after HCG i.m. as well as LH and FSH before and 30 min and 60 min after LH-RH i.v. T, E2, LH and FSH were evaluated by specific RIA. Basal T was significantly decreased in ACi in comparison to normals and to HCi and CHAH. The increase after stimulation with HCG was reduced in all patient groups. Mean E2 before stimulation was altered in none of the groups compared to controls. After HCG there was an inadequate response only in ACi. Before as well as after stimulation with LH-RH, LH and FSH were increased in all patient groups. Our results point to the following: In males with chronic hepatic failure a testes insufficiency often occurs, which may depend on the etiology and the stage of the liver disease. An additional pituitary insufficiency appears not to exist.


Esophageal dysfunction and its pathogenesis in progressive systemic sclerosis. In 25 patients with progressive systemic sclerosis esophageal involvement was studied prospectively by analysing subjective symptoms and radiological and manometric criteria. In all patients abnormal motility could be demonstrated by X-ray and/or manometry: radiologically in 18 (72%), manometrically in 22 (88%) cases. Dysphagia was present only in 11 patients (44%). Six patients (24%) had no subjective symptoms in spite of severe objective esophageal abnormalities. Therefore, the absence of esophageal symptoms does not exclude advanced affliction of the esophagus. To determine the pathogenesis of esophageal dysfunction the effects of 3.5 microgram/kg carbachol and of 0.6 microgram/kg pentagastrin i.m. on the lower esophageal sphincter pressure (LESP), on the amplitude and on the duration of peristaltic esophageal contractions were studied at random in 12 of the patients and 12 normal controls. The results suggest a primary myogenic genesis of the motor abnormalities by atrophy and sclerosis of esophageal smooth muscle.


[Involvement of the exocrine pancreas in Wilson's disease? (author's transl)]. A normal exocrine pancreatic function was demonstrated by the secretin-pancreozymin-test in five patients with Wilson's disease either without (n = 2) or with cirrhosis of the liver but without portal hypertension (n = 3). In another patient with cirrhosis of the liver without portal hypertension the pancreas was normal at post mortem examination. In two patients with cirrhosis of the liver and portal hypertension bicarbonate (n = 1) and amylase secretion (n = 2) were diminished. The regression of portal hypertension under therapy with penicillamine in one of the latter cases was paralleled by the return to normal of exocrine pancreatic function. It is concluded that exocrine pancreatic insufficiency in Wilson's disease is dependent on the development and the progression of chirrhosis of the liver and not due to a primary manifestation of the disease itself.


[Haptoglobin phenotypes and liver cirrhosis. I (author's transl)]. The distribution of haptoglobin phenotypes (Hp) 1--1, 2--1 and 2--2 in 174 patients suffering from liver cirrhosis was determined and compared with a reference group consisting of 194 healthy subjects. The study revealed a high frequency of the Hp 1--1 phenotype (32%) in the patients as compared with the control group (14%). This difference is statistically highly significant (p less than 0.00025). It was calculated that in individuals of type Hp 1--1, the risk of liver cirrhosis is 4.3-fold higher than in persons with the phenotype Hp 2--2.


[Improvement of pathological glucose tolerance by bradykinin in diabetics and in surgical patients (author's transl)]. Intravenous glucose tolerance tests (GTT) were performed in 13 metabolically healthy patients at the first and second day after abdominal surgery. GTT were carried out during an additional infusion of bradykinin (BK) (80 microgram/h) in six of these patients at the first day (group A) and in seven patients at the second day (group B). Furthermore, GTT were performed in six patients with chemical diabetes with and without BK-infusion. In addition, the effect of BK on blood glucose concentration in the postabsorptive state was investigated in nine maturity onset diabetics and in five healthy volunteers. As a control, another nine diabetics received physiological saline. In both groups of surgical patients BK improved glucose tolerance (k-values: group A without BK 1.03 +/- 0.12, with BK 1.31 +/- 0.07; group B without BK 0.85 +/- 0.18, with BK 1.25 +/- 0.21). This was also true in chemical diabetics (without BK 0.81 +/- 0.03, with BK 1.08 +/- 0.04). While BK did not change blood glucose concentration in healthy volunteers, it reduced that of diabetics by 12.2 +/- 1.4% continuously during 100 min. No spontaneous drop of blood glucose was observed in diabetics receiving saline. These results are in good accord with the present view that kinins may play a role within the regulation of carbohydrate metabolism.


[Clinical and in-vitro studies of the therapeutical range of acetylsalicylic-acid to prevent deep vein thrombosis (author's transl)]. In three consecutive studies, acetylsalicyliclysine using the dosages 0.9 g/48 h, 1.8 g/24 h and 3.6 g/24 h, was examined in order to see its effect in preventing deep vein thrombosis (DVT) after elective hip joint surgery. DVT was diagnosed by the 125-i-fibrinogen-test.  No reduction of postoperative DVT was found under any of the administered AS-lysine dosages. The collagen-induced platelet aggregation was significantly decreased in all three groups. However, under the low AS-lysine dosages, aggregation was less inhibited with the incidence of DVT than without DVT. In the group with the 3.6 g-dosage, aggregation was maximally inhibited, without any significant difference related to the occurrence of DVT. The results reveal no therapeutic range of AS-lysine to prevent postoperative venous thrombosis.


Pharmacokinetic investigations in adult humans after parenteral administration of the lysine salt of acetyl-salicylic acid. The lysine salt of acetylsalicylic acid was administered intravenously to four volunteers and intramuscularly to three of them. The drug was tolerated without any observed side effects. Immediately after intravenous application most of the plasma salicylate was acetylsalicylic acid. The highest concentration of acetylsalicylic acid was found after 2 minutes, highest levels of salicylic acid after 60 minutes. Elimination of acetylsalicylic acid was relatively quick within the first period after intravenous administration according to a half-life of 8 minutes. Half-life of salicylic acid was determined to be 3 hours. Intramuscular application results in a constant blood level for a longer period. Bioavailability of acetylsalicylic acid was slightly lower after intramuscular application than after intravenous administration.


Prenatal diagnosis of Tay-Sachs disease in cell-free amniotic fluid. The diagnosis of 6 known Tay-Sachs cases was confirmed by isoelectric focusing of the cell-free amniotic fluid. The presence of an additional--hitherto unknown--heatstable, acid hexosaminidase X in normal and pathological amniotic fluids must be taken into account especially when the heat denaturation method of detecting Tay-Sachs disease is applied. Hexosaminidase X shows some properties similar to those of hexosaminidase B.


[The influence of tinofedrine on fibrinogen and platelet aggregation in patients with recent cerebral infarction (author's transl)]. The influence of Tinofedrine (0.12--0.17 mg/kg. bodyweight) on fibrinogen and platelet aggregation has been investigated in 45 patients (mean age 65 years) with recent cerebral infarction. Depending on the duration of medication a significant decrease of the fibrinogen level as well as of enhanced platelet aggregation has been observed. It is concluded from the present results that the decrease of enhanced platelet aggregation may be mediated by the fall of fibrinogen.


Renal insufficiency in nephrosclerosis (benign nephrosclerosis resp. transition from benign to secondary malignant nephrosclerosis) correlations between morphological and functional parameters. 62 tissue specimens with the only diagnosis benign nephrosclerosis (or benign nephrosclerosis with transition to secondary malignant nephrosclerosis) were investigated attempting to correlate morphological findings (relative interstitial volume of the renal cortex, types of hyalinisation and kinds of periglomerular changes, vessel index) with each other and with the serum creatinine concentration as a parameter of renal function. There are significant correlations in form of exponential and parabolic functions between relative interstitial volume of the renal cortex and the serum creatinine concentration at the time of biopsy. Furthermore 5 types of glomerular and periglomerular changes, which could be discriminated, seem to influence renal function in a different way and at different stages of the disease. An additional factor are the arteriolar changes. There are positive rank correlations between vessel index and serum creatinine concentration as well as between vessel index and relative interstitial volume. In cases with a higher percentage of hyalinized glomeruli more pronounced arteriolar lesions (partly alterations which can be found in secondary malignant nephrosclerosis) were observed. No connections seem to exist between mean blood pressure and the mentioned morphological and functional parameters. The reduction of renal function seems to be caused by tubular and interstitial factors: the often observed atrophy of tubules in fibrotic areas possibly impairs resorptional capacity. The mechanisms of the glomerular-tubular-balance may lead to a diminished glomerular filtration. On the other hand alterations of the capillaries may induce perivascular edema, which, if not reabsorbed, leads to interstitial fibrosis. The produced collagen fibres may reduce the cross sectional area of the postglomerular vessel network. This may lead to a slowing of the renal cortical and glomerular blood flow, thus inducing an increase of the serum creatinine concentration. Weighing all factors, the interstitial fibrosis seems to be the most important.


[Comparative histometrical studies in minimal proliferative intercapillary glomerulonephritis with (minimal changes) and without nephrotic syndrome (author's transl)]. Minimal changes in the glomerular structure and definitively provable only by the aid of morphometric methods. This is of value especially for the minimal proliferative intercapillary glomerulonephritis with and without nephrotic syndrome where, because of the different clinical symptomatology, changes in the morphology may be expected too which however, usually are not recognizable with the methods of light-microscopy. That is why morphometric analyses of kidney tissues of ever ten patients of both groups of the disease were made and the results compared with each after and against normal kidneys. It could be shown that the minimal proliferative intercapillary glomerulonephritis with nephrotic syndrome (minimal changes, lipoid-nephrosis) is accompanied by an increase of local cells, especially the mesangial cells, just as the same disease without nephrotic syndrome. Besides that there exists a clear increase of the mesangiummatrix in the minimal proliferative intercapillary glomerulonephritis without nephrotic syndrome. Because of the morphometric findings it is justified to make a demarcation of both groups of the disease as well as against the mesangioproliferative glomerulonephritis.


[Calcium and phosphate metabolism in hemofiltration (author's transl)]. In 10 patients undergoing hemofiltration treatment acute changes of parameters in the calcium-phosphate metaboism were investigated. Balance studies were also performed in all patients. Control studies were conducted after a 3-month interval in 7 patients. Whereas ionized calcium and 25-HCC remained constant, there was a significant decrease in phosphate, magnesium, fluoride and parathyroid hormone. Corresponding to these results, negative balances could be seen during the course of a hemofiltration treatment: for phosphate a mean value of -593 mg, for magnesium -8.4 mEq and for fluoride -458 microgram. When a calcium content of 3.75 mEq/l was used in the substitution solution, an only slightly positive calcium balance of +1.51 mEq/l (mean value) was found. A significant correlation between calcium and fluid balance was demonstrated by means of 197 filtration treatments of one patient: the calcium balance became negative whenever the fluid loss was greater than 3.86 liters. After a 3-month period no significant changes in the above parameters were found, which indicates, that disturbances in the calcium-phosphate-parathyroid hormone metabolism do not only lie in a reduced renal elimination. Even though our results do not indicate that hemofiltration treatment induces or increases the chances of renal osteodystrophy, the calcium concentration of the substitution solution should be increased to 4.0 mEq/l, in order to guarentee a positive calcium balance even by forced filtration.


Digoxin and digitoxin elimination in man by charcoal hemoperfusion. Since there is no widely used causal means of reducing the severity of massive digitalis intoxication the capability of hemoperfusion with coated activated charcoal to remove toxicologically relevant amounts of digoxin and digitoxin was evaluated in vitro and in man. At a blood flow rate of 100 ml/min the digoxin clearance by hemoperfusion in vitro was 51 +/- 8 ml/min in comparison to 24.3 +/- 11.3 ml/min by hemodialysis. The average hemoperfusion clearance of digitoxin was 31.7 +/- 13.4 ml/min, whereas almost no digitoxin was removed by hemodialysis. These clearance values point to the ability of hemoperfusion of eliminating digitalis glycosides from the blood.  They do not clarify the essential question whether it is possible to lower the toxic concentrations in the tissues.


[Dynamic medical control over the members of the flight crews in the process of long flights]. On the basis of the study of cardiovascular, respiratory, nervous and motor systems of crewmembers (60 people) who made prolonged aircraft flights (over 10 hours) two types of physiological reactions have been defined. One type includes emotional reactions to short-term complications in the flight, and the other involves fatigue and relative exhaustion of the functional systems as a result of strenuous work and adverse flight effects. It has been demonstrated that the dynamic medical control is an important addition to the preflight and interflight physical examinations of the flying personnel.


[Effect of an increased level of hydration on human tolerance to orthostatism and the action of LBNP]. Intake of fluid, water-salt solutions, water and sodium chloride resulted in hyperhydration, the level and duration of which varied with respect to the pattern and composition of the ingredients consumed. As applied to real space flights, fractional consumption of water and sodium chloride proved most promising. This regimen yielded a distinct and prolonged hyperhydration and incrased orthostatic and LBNP tolerance of the test subjects.


[Change in human kidney activity in passive orthostatism and head-down tilting]. Changes in the natriuretic and water excretory renal functions of healthy people during tilt table tests--with the head-end lifted upwards at an angle of 45 degrees and lowered at an angle of -15 degrees--were investigated. The renal excretion of sodium, water and osmotically active substances decreased drastically during the first 20 min of the headdown tilting and continued to fall down during the next 20 min. These changes were induced by an increase in the rate of tubular reabsorption of filtrate, sodium and osmotically free water rather than by a significant decrease of glomerular filtration rate. After tilting to the horizontal position circulation and glomerular filtration parameters rapidly returned to the normal. However, sodium clearance, diuresis and osmolar clearance remained decreased till the end of the experiment due to the further increase in the tubular reabsorption rate of sodium and water. During head-down tilting an increase in natriuresis, diuresis and osmolar clearance was seen which was related to an increase in the glomerular filtration rate and a decrease in the tubular reabsorption rate of filtrate, sodium and osmotically free water.


[Constancy of the circadian system of the body]. With respect to the biorhythmological selection of cosmonauts the concept of the biorhythmological status is understood as a sum total of biorhythmological properties of the human body. Two components of the biorhythmological properties of the human body. Two components of the biorhythmological status--constancy and lability of the circadian system--are described. Their interaction is discussed from the point of view of the hierarchical principle of the arrangement of the circadian system. Certain methods of quantitative evaluation of constancy of circadian rhythms are presented. Particular attention is given to the assessment of stability of the position of circadian rhythms on the 24-hour scale.


[Dynamics of the biochemical makeup of the blood in cosmonauts during flights]. Prolonged space flights (15 to 63 days) led to changes in the biochemical composition of the blood that were observed both during and after flight. Blood samples were withdrawn inflight, stored in a special device onboard and analyzed on return to Earth. The data obtained in real flights were compared with those from the 30-day simulation flight. In real and simulated flights the urea content showed the most significant changes. Inflight it increased to 40 mg% versus 31 mg% preflight. The urea content grew on the 3rd-5th flight day, reaching maximum on the 15-30th day and decreasing again afterwards. The content of glucose and inorganic phosphorus increased slightly whereas that of acid-soluble and lipid phosphorus remained unaltered. The level of cholesterol decreased. The striking similarity between the changes in blood biochemistries during real and simulated flights suggests that they are induced by factors other than weightlessness.


[Dynamics of the disturbances in pilot activities in hypoxia]. Changes in the structure of the work done by aircraft flyers during piloting and oxygen starvation were studied. The experiments were carried out on 10 pilots who performed simulation flights while breathing hypoxic gas mixtures containing 10.5% O2 (at an altitude of 5000 m) or 9.6% O2 (at an altitude of 5600 m). These findings suggest that the earliest sign of disordered piloting during hypoxia was a delayed formation of controlling actions. At greater hypoxia noticeable changes were seen in the structure of motor activities together with distinct disturbances of coordination relations of muscles-antagonists involved in the realization of controlling movements. The sensory component suffered from the hypoxic effect to a lesser extent. Complex forms of the mental activity proved to be most resistant to hypoxia.


[Combined effect of hyperoxia, hypobarism and physical work on the rate of methyl ketone excretion from the human body]. When working under the conditions of lowered atmospheric pressure (energy expenditures 400 kCal/hour, barometric pressure 308 mm Hg, oxygen breathing, comfortable environmental parameters), the test subjects showed an increased rate of methyl ketone excretion in the exhaled air. The content of acetone in the excreted methyl ketones was 70%. The methyl ketone excretion with perspired water developed uniformly.


[Basic results of an experiment with mammals on the Kosmos-782 biosatellite]. The rat experiments carried out onboard the biosatellite Cosmos-782 contributed to our understanding of mechanisms of animal adaption to prolonged weightlessness. Postflight analysis helped to study nonspecific changes related to the stress-reaction accompanying space flight and return to the Earth gravity as well as specific changes associated with functional unloading of the musculoskeletal system in weightlessness. The flight results confirmed the previously made conclusions concerning possible adaptation of mammals to prolonged weightlessness and lack of pathological changes in vital weightlessness. They included: metabolic and hormonal changes, muscle atrophy, osteoporosis and delayed bone growth, decrease of ATPase activity of myocardial myosin, inhibition of erythropoiesis.


[Spermatogenesis in dogs during chronic gamma irradiation over years and in the aftereffect period]. Morphological parameters of spermatogenesis of 60 test and 12 control dogs exposed to a 6-year irradiation with total doses of 21 to 1140 rad were studied. The capacity for reparative regeneration of testes was maintained during the 5-6 years of irradiation at a dose rate of 0.06 and 0.17 rad/day. Early signs of radiation injury of testes were clearly observed during the first years of irradiation at a dose rate of 125 rad/year and progressively developed with an increase in the total dose. Inhibition of spermatogenesis reached maximum (atrophy of the spermatogenic epithelium, depletion of canaliculi) by the end of the first year of combined irradiation (190 rad/year). Spermatogenesis returned to normal in the animals that received a total dose of 570 rad during a 3-year irradiation exposure and were sacrificed 4.5 years after the onset of the experiment.


[DNA content in the organs of animals in space flight on the Kosmos-690 satellite]. The DNA content in the liver, spleen and bone marrow of white rats exposed to a prolonged gamma-irradiation at a dose of 220 and 800 rad on the 10th day of the 20.5-day space flight and the ground-based synchronous experiment was measured. Space flight factors produced a modifying effect on the postradiation changes in the DNA content. This modifying influence was detected in all organs tested, although in a different degree, and involved an enhancement of the radiation effect which was associated with retardation of postradiation regenerative processes.


[Blood coagulation state on exposure to prolonged hypokinesia]. The effect of 14- and 30-day hypokinesia on hemocoagulation of rabbits was studied. Hypokinesia caused noticeable changes in the hemostatic system. By the 14th hypokinetic day the experimental animals developed hypercoagulation which in some cases ended in intravascular blood-clotting. By the 30th hypokinetic day there was a decrease in the total blood coagulatory capability which to be associated with the utilization of procoagulants during blood clotting and an increase in the anticoagulant activity in response to primary hypercoagulemia. Thus, hypokinesia-induced changes in the blood clotting system develop like the thrombohemorrhagic syndrome.


[Combined action on the body of carbon monoxide and normobaric hyperoxia]. Thirty-day experiments on white male rats were carried out to determine the combined effect of carbon monoxide and hyperoxic atmosphere on the animal body. The two factors showed an antagonistic biological effect, the influence of hyperoxic atmosphere prevailing over that of carbon monoxide. It is suggested that during a combined exposure of animals to the two factors maximally allowable concentrations of each can be used without any corrections.


[Blood lipid changes in rats in hypoxia]. Changes in the total lipid spectrum of serum of rats exposed to acute hypoxia were examined. Quantitative measurements of lipids showed a decrease of total lipids and a redistribution of lipid components in absolute and relative values. A distinct decrease in the quantity of cholesterol ester and a concomitant increase of free cholesterol, an elevation in the relative content of free fatty acids and emergence of diglycerides were noted. The qualitative composition of phospholipids remained unaltered, whereas the absolute amount of glycerophosphates, lysoforms of phosphatids, phosphatid acids and lecithin fraction increased. The changes in the ratio of lipid components are closely connected with the qualitative and quantitative changes in the composition of serum lipoproteins.


The pathogenesis of papillary muscle rupture complicating myocardial infarction: hemorrhage accompanying contraction band necrosis. Although frank rupture of the papillary muscle complicating myocardial infarction is gaining widespread interest as its incidence continues to rise, the mechanism of rupture remains unclear. Of all patients who died with myocardial infarction and who came to autopsy at this institution over the past 21 years, 13 were found to have papillary muscle rupture. Twelve of these 13 had severe contraction band necrosis with interstitial hemorrhage in the areas surrounding the site of rupture. The hemorrhages infiltrated the interstitium and appeared to have dissected both longitudinally and transversely through the myocardium. In contrast, those patients with papillary muscle infarction without rupture were found to have coagulation necrosis. These findings suggest that the interstitial hemorrhages occurring with contraction band necrosis may act as dissecting masses of blood, thereby causing the rupture.


[Hemodynamic and cardiac cycle phase structure study of the Saliut-4 crew]. The paper gives the results of physical examinations of P.I. Klimuk and V.I. Sevastyanov during their flight aboard the orbital station Salyut-4. The examinations were carried out by means of the Polynomial-2 device at rest and under the conditions approximating basal metabolism. Since the end of the first flight week the circulation parameters did not differ substantially from the preflight values. Stroke volume and cardiac output increased slightly. In weightlessness circulation parameters varied with respect to the work done by the cosmonauts. On the first postflight day peripheral resistance, arterial pressure and cardiac output were increased.


Granular and agranular cell counts in the juxtaglomerular apparatuses of rats with unilateral renovascular hypertension. Counts were made of granular and agranular cells in the juxtaglomerular apparatuses of rats with unilateral renovascular hypertension, using light and electron microscopy. Both granular and agranular cells may appear binucleated; therefore, nuclear counts need to be corrected by 4 to 8 per cent to get true cell counts. The polar cushion (Polkissen) corresponds to the cells included in the juxtaglomerular cell count, which is really a nuclear count. Interstitial or inflammatory cells may lie close to the polar cushion and should be excluded from the counts. The polar cushions in sham-operated rats contained mostly agranular cells: less then 6 per cent of the cells were granular. Most of the granular cells lay outside the polar cushion in afferent and efferent arteriolar walls. With acute hypertension the cells in the polar cushion increased 26 per cent due to increases in both granular and agranular cells, with the result that 11 per cent of the cells were granular and 89 per cent agranular. The number of granular cells seemed to decrease with chronic hypertension while the number of agranular cells remained elevated. This suggests the agranular cells have a function which is independent of that of granular cells.


Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Adult Sprague Dawley rats were subjected to spinal cord trauma at the lower thoracic-lumbar levels utilizing a weight dropping technique onto the surgically exposed dorsal surface. The experimental conditions of trauma consistently produced severe paraplegia without spontaneous movement of the hindlimbs, a sensory level, and neurogenic bladder dysfunction. Changes in blood vessels and the development of tissue necrosis were studied in a posttrauma time sequence by light and electron microscopy. Fibrinoid necrosis and disruption of major arteries as well as veins were observed immediately after impact, antedating the evolution of parenchymal necrosis. A fusiform zone of spinal cord necrosis, involving the complete cross-sectional area beneath the site of impact, evolved over a period of 8 to 24 hours, being initially complete in the gray matter by 4 hours and thereafter in the white matter. Ultrastructural observations revealed that the evolution of necrotic cellular constituents was piecemeal. Except for the occurrence of intracellular calcification and heterophagocytosis in the traumatized tissue, the electron microscopic features of cellular necrosis were comparable to those of postmortem spinal cord autolysis, studied in parallel. The observations are consistent with trauma producing ischemic necrosis, resulting from major blood vessel disruption occurring at the moment of impact.


Pathology of experimental spinal cord trauma. II. Ultrastructure of axons and myelin. Adult male Sprague Dawley rats were subjected to spinal cord trauma of the lower thoracic-upper lumbar spinal cord using a weight dropping technique onto the surgically exposed dorsal surface. This experimental model, which results in severe paraplegia and development of complete segmental necrosis, was studied in a time sequence varying from immediately to 30 days afterward by electron microscopy, in order to characterize the pathologic changes in axons and myelin in the area of impounding. The results revealed tubulovesiculation within axons immediately posttrauma. Axonal fragmentation, axonal and adaxonal swelling accounted for the progressively increasing spongy appearance of the white matter. Beginning at 30 minutes and progressing until completion of tissue necrosis at 8 to 24 hours, axonal necrosis characterized by a finely granular alteration gradually evolved. Spheroids containing increased mitochondria, neurofilaments, lysosomes, and smooth endoplasmic reticulum appeared both in and peripheral to the zone of necrosis. Axonal calcification, rarely observed within 30 minutes, appeared maximally after the evolution of tissue necrosis. Two basic abnormalities of myelin were found: vesicular degeneration and intramyelinic vacuolization. These characteristically occurred late and involved fibers with abnormal axoplasm and were interpreted as being secondary in origin.


Effects of two types of motor practice on stuttering adaptation. The present study identifies and compares the effects of two types of motor practice on stuttering adaptation. The study was designed to determine if whispered reading practice affects stuttering adaptation, and if practice in reading aloud is superior to whispered reading in promoting adaptation. In a control condition, eight stutterers read one of two matched passages aloud five times in succession. In an experimental condition, the remaining passage was read aloud on the first and fifth trials, and was read in a whisper on Trials 2, 3, and 4. The results indicated that (1) the stutterers' adaptation in the control condition was similar to the typical course of adaptation, (2) the three intervening whispered readings in the experimental condition neither inhibited nor facilitated adaptation, and (3) practice in reading aloud was superior to whispered practice in promoting stuttering adaptation. It was concluded that whispered reading practice does not facilitate stuttering adaptation when the measurement of that process requires reading aloud. Traditionally, adaptation has been measured only during reading done aloud. Consequently, practice in reading aloud has the greatest positive influence on the adaptation process.


Performance of children with good and poor articulation on tasks of tongue placement. This study determined whether children could learn to replicate four positions of lingual-palatal contact with and without topical anesthesia that eliminated touch-pressure sensations. First-grade boys, nine with good articulation skills and nine with poor articulation skills, were used as subjects. Results suggest that individuals are able to learn nonspeech tasks of tongue positioning by relying on muscle spindles or deep receptors within the tongue, or both, or by relying on lingual touch-pressure or other surface receptors within the tongue, or, by a combination of deep and surface receptors of the tongue. Further, tongue positioning need not be dependent on touch-pressure or superficial tactile mechanisms. Children with relatively severe articulation problems performed more poorly on the tasks of precise tongue placement than children with good articulation skills. And finally, children with relatively severe articulation problems may be able to improve their initially poor performance on tongue placement tasks with specific training on those tasks, implying that this group did receive the intraoral sensory feedback necessary to learn the task, but that more experience was needed for the learning to occur.


Room acoustics effects on monosyllabic word discrimination ability for normal and hearing-impaired children. The monosyllabic work discrimination of normal and hearing-impaired children was evaluated in situations selected to simulate acoustical conditions in current educational environments. All listeners were tested in a high-fidelity (loudspeaker-aided) condition under 12 combinations of reverberation and noise. Hearing-impaired subjects were also evaluated in the same 12 conditions while listening through a monaural hearing aid. Performance of the normal-hearing group was superior to the hearing-impaired listeners in all environments. Results suggest that classroom acoustics should be considered a critical variable in the educational achievement of children.


The effects on stuttering of self-recording the frequency of stuttering or the word "the". The effect of self-recording the frequency of stuttering or the word "the" during spontaneous speech by three adult stutterers was assessed within a single-subject experimental design. The effect of these procedures on stuttering frequency, use of the word "the," and speech rate differed for each subject. Subject 1 showed no systematic change in stuttering and an initial increase in "the" responses. Subject 2 reduced stuttering to almost zero during self-recording conditions. Subject 3 increased stuttering during self-recording stuttering and self-recording "the" conditions. These results, which indicated that self-recording procedures have a variety of effects on the stuttering behavior of different individuals, are not consistent with previous studies that have shown only reductions in stuttering during self-recording conditions.


Some airflow, volume, and duration characteristics of oral reading. Inspiratory and expiratory airflow (oral + nasal), volume, and duration characteristics during oral reading were investigated for eight young adults. Flow signals, sensed through a facemask-pneumotachometer-pressure transducer system, were quantified and analyzed by a computer program. Results showed that the modification of volume and flow during oral reading was primarily related to the timing of inspiratory and expiratory phases and secondarily to the magnitude of oronasal air volume. Effects of linguistic constraints were observed in inspiratory behavior, within and between sentences. Connected utterances showed lower and more variable peak flows than those reported for isolated syllables or words.


Use of optical distance sensing to track tongue motion. We have designed a device that uses a reflected-light-sensing technique to monitor tongue movement in the frontal oral cavity. The sensing unit is composed of a LED light source and a phototransistor, mounted together onto an artificial palate, and attached to the had palate. The basic sensing function of this unit is governed by the formula r/(r2 + xo2)3/2 rather than by the inverse square distance law. In this equation, r is the distance between the sensor and the reflector, namely, the tongue surface. The xo is the separation between the source and the photosensor. Two potential problems, the beam dispersion effect of the light source and the nonparallel movement of the tongue, were anticipated. They can be theoretically represented or technically prevented. The softness of the tongue and the protuberances of its surface are also favorable aspects of this method, creating special light reflection from the tongue surface. The available output function was from 0 to 40 or 50 mm. This gives the device the capability of detecting both vowel and consonantal articulation. The method can be useful to further speech research and the development of a language teaching aid system.


Speech-discrimination scores modeled as a binomial variable. Many studies have reported variability data for tests of speech discrimination, and the disparate results of these studies have not been given a simple explanation. Arguments over the relative merits of 25- vs 50-word tests have ignored the basic mathematical properties inherent in the use of percentage scores. The present study models performance on clinical tests of speech discrimination as a binomial variable. A binomial model was developed, and some of its characteristics were tested against data from 4120 scores obtained on the CID Auditory Test W-22. A table for determining significant deviations between scores was generated and compared to observed differences in half-list scores for the W-22 tests. Good agreement was found between predicted and observed values. Implications of the binomial characteristics of speech-discrimination scores are discussed.


Language and sensorimotor development during the early period of referential speech. The relation between sensorimotor attainments and linguistic development in children using referential speech at the single- and two-word utterance levels was examined. When age was controlled, the sensorimotor task performance of normal children who produced two-word utterances was highly similar to that of normal children limited to single-work utterances. Identical findings were observed for language-disordered children functioning at the single- and two-word utterance levels. In addition, several children's performances on the sensorimotor tasks were below the level previously thought necessary for the emergence of referential speech. The position is taken that the relationship between sensorimotor development and linguistic development is not as close as has been presumed.


Understanding indirect requests: an investigation of children's comprehension of pragmatic meanings. Two experiments examined four-, five-, and six-year-old children's understanding of indirect requests. The experimental tasks required the children to judge the appropriateness of a listener's response to indirect requests involving an affirmative syntactic construction (Can you shut the door?), requests containing a negative element (Can't you answer the phone?), and requests for the state of affairs mentioned in the predicate to be changed (Must you play the piano?). Even the youngest age group exhibited an understanding of the first two types of indirect requests. However, only the six year olds showed any understanding of requests for a change in the state of affairs mentioned in the predicate. Possible factors responsible for children's difficulty with these requests are discussed.


Laryngeal muscle activity during stuttering. Laryngeal muscle activity during fluent and stuttered utterances was investigated via electromyography. Analysis revealed that stuttering was accompanied by high levels of laryngeal muscle activity and disruption of normal reciprocity between abductor and adductor muscle groups. Results are interpreted as demonstrating the existence of a laryngeal component in stuttering and showing a strong correlation between abnormal laryngeal muscle activity and moments of stuttering.


A laterality effect in isometric and isotonic labial tracking. Hemispheric dominance for sensorimotor control of lip activity was investigated by use of a pursuit auditory tracking task. This task involves continuous frequency matching of a computer-generated target tone and a subject-controlled cursor tone. Thirty right-handed subjects were tested under isometric lip and hand control, and 20 right-handed subjects under isotonic lip control. Subjects tracked 10 1-min trials under each laterality condition--cursor/right ear, target/left ear, and vice versa. In both experiments tracking performance was better when the lip-controlled cursor tone was presented to the right ear (hence direct contralateral route to left hemisphere). A significant (p less than 0.05) cursor/right-ear advantage was found under isometric hand-tracking. Analysis routines examined relative laterality advantages across several time intervals within each 1-min trial. Consistent lateralization scores in favor of cursor/right-ear presentations (REAs) were independent of the time interval measured. For isometric tracking, 58% of subjects having laterality advantages (p less than 0.10) revealed REAs. For isotonic tracking, 71% of subjects revealed REAs. Implications of the latter finding are discussed relative to a left hemisphere mechanism specialized to integrate movement-generated auditory feedback with dynamic kinesthetic information from the articulators.


A right-ear effect for auditory feedback control of children's newly acquired phonemes. To determine the relative importance of binaural, right-ear, and left-ear auditory feedback control on the correct production of newly acquired articulatory patterns in children, 40 children exhibiting misarticulations were tested under four experimental conditions. The children were individually administered a shortened version of the Deep Test of Articulation (McDonald, 1964) under (1) a no-masking condition, followed in a counterbalanced order by readministration of the Deep Test under conditions of (2) binaural masking, (3) monaural right-ear masking, and (4) monaural left-ear masking. Correct articulatory production by the children was significantly reduced under binaural and monaural right-ear masking. There was, however, no significant reduction in the children's correct production under the condition of monaural left-ear masking. The results extend previous findings of right-ear superiority for children's auditory processing of externally produced stimuli to the closed-loop auditory feedback control of children's own speech production.


Stuttering as operant behavior: effects of the verbal stimuli wrong, right, and tree on the disfluency rates of school-age stutterers and nonstutterers. This study assessed the effects of the verbally presented stimuli wrong, right, and tree on the frequency of disfluencies during oral reading by 18 school-aged stutterers and 18 matched nonstutterers. No differences were found between the three stimulus words' effect on the disfluency rate of either subject group. Because decreases in the disfluency rates of stutterers were observed during the presentation of all three stimulus words, the data failed to support the operant model. A discussion of theoretical and experimental implications is given.


Factors influencing morbidity and mortality in esophageal carcinoma. In 1977, 152 patients with carcinoma of the esophagus were admitted under our care. The lesions were located from the hypopharynx to the cardiac portion of the stomach. A prospective study was conducted and the results (mortality and morbidity) were analyzed by computer. Resection was possible in 88 patients and a bypass procedure in 15. On exploration in five patients, the disease was found to be so extensive that no further operative procedures were undertaken. The mortality rate was high, hospital deaths being included in the operative mortality statistics. The best results were obtained by applying the Lewis-Tanner one-stage esophagectomy. When the disease was extensive, a bypass procedure using the Kirschner operation and postoperative irradiation was the method of choice. When the general condition of the patient was poor, the best procedure was a staged esophagectomy, with the reconstruction being undertaken at a later date.


Bronchopleural fistula. Thirteen-year experience with 77 cases. Bronchopleural fistula, although reduced in incidence in recent years, remains a grave complication of pulmonary disease and of pulmonary resection. In a series of 77 patients treated for bronchopleural fistula over a 13 year period, 49 of whom had postresection fistulas, only 44 (57.1 percent) were cured of the fistula and 15 (19.5 percent) died. Prevention assumes great importance. Key factors in prevention are avoidance of pulmonary resection in tuberculous patients with positive sputum; overzealous dissection of the bronchus; a long bronchial stump; tumor in the bronchial stump; contamination of the pleural cavity; and too little tissue left behind to fill the pleural space. Treatment should be surgical. In none of the six patients treated conservatively was the fistula obliterated. Seventy-one patients were treated surgically, and 133 operations were needed to effect fistula obliteration in the 44 patients (62 percent) in whom this was achieved. Adequate surgical drainage has always been the sine qua non of effective treatment, and yet this alone brought about closure of the fistula in only nine patients. Early resuture of the bronchial stump succeeded in only two of five patients. Thoracoplasty combined with drainage effected closure in seven of 11 patients. The highest rate of fistula closure with the lowest mortality occurred among the 20 patients who underwent myoplasty, usually combined with a limited thoracoplasty. In this group, the fistula was obliterated in 16 patients, with one death.


Long-term clinical and hemodynamic evaluation of the Ionescu-Schiley pericardial xenograft and the Braunwald-Cutter and Björk-Shiley prostheses in the mitral position. Single mitral valve replacement was undertaken in 220 patients between March, 1971, and October, 1977. Bjork-Shiley prostheses (BS) were inserted in 42 patients, Braunwald-Cutter prostheses (BC) in 52, and Ionescu-Shiley pericardial xenografts (PX) in 126. No attempt was made at randomization. The actuarial survival rate was 81.9 +/- 12.8 percent at 7 years for patients with BS prostheses, 41.7 +/- 22.9 percent at 6 years for patients with BC prostheses, and 89.0 +/- 9.3 percent for patients with PX valves 7 years following valve replacement. Of the late deaths in patients with BC prostheses, 62.5 percent were valve related. The incidence of thromboembolism was 4.7, 1.8, and 1.5 episodes per 100 patient-years in the BS, BC, and PX groups, respectively. Long-term anticoagulation was used only in patients with BS and BC prostheses. Late postoperative hemodynamic studies were performed in six patients each with BS and BC prostheses and in 29 patients with PX valves. The mean diastolic gradients at rest were 6.2, 8.3, and 6.4 mm. Hg in the respective groups. The corresponding figures for calculated valve area were 1.8, 1.6, and 2.0 sq. cm. There was no statistically significant difference between the data recorded from the three groups of patients except for the survival rate of the BC prosthesis and the PX valve. The BS prosthesis and the PX valve have similar durability and hemodynamic performance for an almost identical duration of follow-up. Because of the improved quality of life and reduced morbidity without anticoagulants, we are using the PX valve exclusively for heart valve replacement.


In vitro hydrodynamic comparison of mitral valve prostheses at high flow rates. A pulse duplicator system for evaluating the hemodynamic performance of mitral prostheses is described. Under conditions stimulating normal resting physiology, all valves tested had measurable but acceptably small pressure drops. Under conditions simulating exercise, all were moderately to severely stenotic. Valves with nearly equal mounting diameters were compared. The Hancock, Beall, and Starr-Edwards valves (Group A) were found to be significantly more stenotic than the Björk-Shiley, Cutter-Cooley, Ionescu-Shiley, and Lillehei-Kaster valves (Group B). In the 29 to 30 mm. mounting diameter size at cardiac outputs of 5 and 9 L. per minute, Group A had average pressure drops of 3.2 and 10.5 mm. Hg and Group B, pressure drops of 1.6 and 5.3 mm. Hg, respectively. In the 24 to 26 mm. mounting diameter size, at cardiac outputs of 9 L. per minute, all the valves had critically large pressure drops (9 to 17.6 mm. Hg). The standard Gorlin formula is inappropriate for computing the orifice area of prosthetic valves. The discharge coefficient for a valve (a measure of how well the valve uses its primary flow area) and a performance index (a measure of how well the valve uses its mounting area) have been computed from a knowledge of the orifice size, without the necessity of assuming a value for the discharge coefficient required by the Gorlin formula. The biological valves (Hancock and Ionescu-Shiley) provide an efficient orifice for fluid flow at the free leaflet margins and have large discharge coefficients. On the basis of the fluid dynamic equation of motion, steady flow, root mean square (RMS) flow, and peak flow, combined with the appropriate transvalvular gradients, were all shown to yield equally accurate characterizations of valvular hydrodynamic performance. Mean flow, unfortunately the only value obtainable clinically, yielded effective orifice areas 10 percent smaller than either of the other three flow values.


Non--cloth-covered caged-ball prostheses. The second decade. The Starr-Edwards Models 6120 mitral and 1200/60 aortic valves are caged-ball prostheses with cloth-covered sewing rings and bare-metal struts. Introduced in 1965, they have been in continuous clinical use longer than any other currently available heart valve prostheses. Late results with this valve are analyzed and compared with recent series employing other current valve prostheses. One hundred thirty-four mitral 6120 prostheses were inserted at the University of Oregon Health Sciences Center from 1965 through 1977, with 118 operative survivors followed for  a mean of 5.4 years. Twelve-year survival rate (+/- standard error) was 50 (+/-8) percent. Twelve percent of late deaths were valve related. Eighty-eight (+/-5) percent of valves were still in place at 12 years. The embolic rate was 5.8 (+/-1.0) percent per patient-year for all emboli and 2.2(+/-0.6) percent per patient-year for serious emboli. Two hundred forty-nine operative survivors among 282 patients undergoing aortic valve replacement during the same period of time were followed for a mean of 4.3 years. Twelve-year survival was 61 (+/-6) percent and the removal-free rate was 92(+/-5) percent. Six percent of late deaths were valve related.  Embolic rates were 5.0 (+/-.7) percent and 1.8 (+/-.4) percent per patient-year for all emboli and serius emboli, respectively. Structural failure, specifically ball variance, was not encountered with this prosthesis. Ninety percent of 10 year survivors are in N.Y.H.A. Functional Class I or II. There was one anticoagulant-related death in 1,698 patient-years of follow-up. The current non--cloth-covered caged-ball valves provide unquestionable durability and well-documented results into their second decade of use. They provide a base line for comparison with newer prostheses and offer a valid, current choice for both aortic and mitral valve replacement.


The surgical anatomy of Kent bundles based on electrophysiological mapping and surgical exploration. The development of the procedure for interruption of a Kent bundle for the correction of the tachyarrhythmias associated with the Wolff-Parkinson-White syndrome has been hampered by the lack of anatomic descriptions of the pathways. Only 21 descriptions are given in enough detail for guidance to the surgeon. Our experience with our first 100 patients operated upon for serious dysrhythmias associated with Kent bundles has supplemented this information. In our first 40 patients the Kent was divided in 22 of 39, one having elective and four having forced interruption of the His bundle, with success in 28. In the next 60 the Kent was divided in 52 of 59 attempts, one had elective and three had forced His bundle interruption, and the success rate was 56 of 60 patients. This increased success occurred because we learned the following: (1) The anomalous pathways are best approached through the atrium and can be for out in the  fat, even subepicardial in the coronary sulcus or adjacent to the anulus. (2) Interruption should be started with an incision made just above the anulus fibrosus. (3) Posterior septal pathways can be adjacent to the His bundle or in the septum from this point posteriorly to the crux. (4) Anterior septal pathways can be divided and the His bundle protected. The details for the approach to the right and left free wall, posterior septal, and anterior septal pathways will be given. The approach to all pathways is now safe enough to allow the surgeon to offer this operation to patients with life-threatening tachyarrhythmias as well as the ones with rhythm disturbances that are either burdensome or impossible to treat medically.


Composite replacement of the aortic valve and ascending aorta. This report comprises 16 consecutive patients with ascending aortic aneurysms caused by cystic medical necrosis. We replaced the ascending aorta and aortic valve with a tightly woven Dacron graft containing a Lillehei-Kaster valve prosthesis and implanted the coronary ostia in the sides of the graft. All but two patients had massive aortic insufficiency. Postoperative catheterization was performed in 13 patients, and all surviving patients have been seen within the past 6 months. There was one perioperative death (6 percent) and two late deaths. Eleven survivors are in Class I and two are in Class II (N.Y.H.A.). Angiographically demonstrated late complications have included psuedoaneurysms of the coronary ostium (two), paravalvular leak (one), and pseudoaneurysm of the distal suture line (one). Two of these four patients were asymptomatic. Two of the four patients have had successful repair of these defects and a third is awaiting operation. Compositive replacement carries a low operative risk and minimizes problems of intraoperative bleeding. In view of the incidence of late suture line problems, routine angiography 6 to 12 months postoperatively is recommended. If new symptoms occur or if there is a change in the cardiac silhousette on chest roentgenogram, the patient should be recatheterized.


Lymph node mapping and curability at various levels of metastasis in resected lung cancer. By means of lymph mapping, the prognosis significance of lymph node metastasis in lung cancer was studied in 270 patients who had undergone radical operations--pulmonary resection combined with complete mediastinal lymph node disection, which is used for patients in whom all cancer could thereby be ablated. Mediastinal lymph node metastasis was found in 64 patients, and 12 patients lived 5 years or more (an absolute 5 year survival rate of 18.8 percent). After radical surgery, there was a significant difference between the prognosis for patients who had metastases to the subcrainal lymph nodes as compared to the prognosis for those who did not. The 5 years survival rates were 9.1 percent and 29.0 percent, respectively. On the other hand, prognosis was not significantly affected by involvement or noninvolvement of the superior mediastinal, paratracheal, tracheobronchial, pretracheal, and the subaortic and para-aortic lymph nodes. No significant difference in survival was detected between patients who were given adjuvant therapy and those who were not. Lymph node mapping gives valuable prognostic information.