[The influence of biophysical factors on biological oxidation and redox processes. 17. Changes in electron transfer and of oxidative phosphorylation steps in liver mitochondria after ultrasonic treatment (author's transl)]. Ultrasonic treatment in vivo brought about distinct changes in liver mitochondria which developed in two directions as to oxygen consumption and oxidative phosphorylation. An increase of oxygen incorporation occurs with short term as well as with long-term experiences. The ratio P/O which expresses the step of oxidative phosphorylation decreases to 1 in the course of one hour after ultrasonic treatment. The results obtained and the supposition that they are related to modifications of NAD-coenzymes and flavoproteins, likewise of the activity of succinic dehydrogenase, of NADH2-cytochrom-c-reductases and cytochrom-c-oxidase, lead to the conclusion that ultrasonic energy is a factor intensifying the transfer of reduced equivalents in the shortened respiratory chain, a factor disturbing electron-proton transfer in the normal respiratory chain of NAD-coenzymes, and a releasing factor for two of the sites of coupling electron transfer with oxidative phosphorylation.


Changes of the activity of certain lysosomal enzymes in the blood serum of whole-body irradiated rats. The activities of acid phosphatase, beta-glucuronidase, beta-galactosidase, acid ribonuclease, and acid deoxyribonuclease were studied in the blood serum of rats after total, either single or franctionated, exposure. After the single, total exposure to 800 R of X-rays, remarkable increases in the activities of acid phosphatase and acid deoxyribonuclease were observed in the blood serum immediately after the irradiation. At later stages were observed statistically significant decreases of beta-glucuronidase and beta-galactosidase in the rat blood serum after the total, single exposure. The serum acid ribonuclease activity remained essentially unaltered over the whole time interval of interest. In the blood serum of the rats exposed to total, fractionated irradiation, statistically significant decreases in the acid phosphatase and beta-glucuronidase activities were observed 1 and 8 days after completing the irradiation. In the case of beta-galactosidase, this decrease lasted even up to the 15th day after the end of irradiation. The activities of serum acid deoxyribonuclease and acid ribonuclease exhibited no statistically significant changes.


The effect of X-irradiation on phytohemagglutinin (PHA)-stimulated rat lymphocytes. The effect of X-irradiation on PHA-stimulated rat lymphocytes has been investigated. The animals were exposed to doses of 100 to 800 R. Blood obtained by cardiac puncture was defibrinated and the lymphocytes sedimented by Dextraven. Lymphocytes were separated from supernatant and cultivated for three days in standard medium supplemented with rat serum and PHA. It was found that irradiation reduces the percentage of blast cells in function of the doses of irradiation. This reduction is accompained by an increased number of macrophage-like cells. The labelling index with tritiated thymidine in PHA-transformed lymphocytes was also reduced following irradiation.


[Carcinoma of the penis: symptomatics, therapy and prognosis (author's transl)]. During the period from 1912 through 1970, 150 cases with a carcinoma of the penis have been examined and treated in the clinics of the university of Göttingen. The preferred age of incidence was between fifty to sixty years. Primary phimosis could be verified in 17.3%, a secondary phimosis, caused by the tumor, in 5.3%. Eighty patients were graded stage I, seventy stage II and more advanced stages. Metastases to the inguinal region were observed in 60.6% out of 99 patients who had undergone lymphadenectomy. Distinctly enlarged inguinal lymph nodes proved to be metastases in only a third of the cases. The staging of a case with carcinoma of the penis, therefore, is not possible by means of clinical criteria alone but needs also a biopsy from the inguinal region. The 3-year, 5-year, and 10-year survival rates amounted to 52.5%, 46.7% and 32.4% and did not depend on treatment techniques. The most promising survival rate resulted from a combination of surgical treatment with high-voltage therapy.


[Irradiation therapy of vertebral angionomas: results in 62 patients during the years 1939 to 1975 (author's transl)]. 62 cases with vertebral hemangiomas and clinical symptoms from 1939-1975, treated by radiotherapy are reported. In about 60%, radiotherapy resulted in permanent significant improvement or freedom of angioma related symptoms. In 7 cases with symptoms of severe compression of the myelon, decompressive laminectomy was performed, followed by radiotherapy. The radiation dose in the vertebrae were: 3000-5000 rd, 100-200 rd single dose, 5 times per week. Hemangiomas of the vertebrae are an accepted indication for irradiation. We recommend doses about 4000 rd, 150-200 rd single dose, 5 times per week. In cases with severe cord compression decompressive surgery is to be performed first.


[Struma maligna after X-ray irradiation of the neck (author's transl)]. Case report of a papillary thyroid gland carcinoma which was possibly induced by the irradiation of a parotid gland carcinoma.


[Tests of the sensitivity of histologically characterized carcinomas of the ovary or corpus to 4-hydroperoxicyclophosphamide, amethopterine, mitopodozide and VM-26 sandoz, using the technique of primary culture (author's transl)]. Cells from three carcinomas of the uterine corpus and from 14 ovarian carcinomas have been cultured in vitro by the monlayer and sandwich methods. They were evaluated on the basis of morphological criteria after 24 hours of incubation with 4-hydroperoxicyclophosphamide, amethopterine, mitopodozide and VM-26 Sandoz, using two dose ranges in each case. The index of 3H-thymidine was determined by means of two parallel experiments. Later results concerning pharmacokinetics of the cyclophosphamide have lead us to apply the technique of primary culture. Owing to the long duration of the incubation period, the 4-hydroperoxicyclophosphamide with its secondary and degradation products can influence the greatest possible numbers of cells through several phases of the cell cycle, thus obtaining an approach to in-vivo kinetics. A concentration of substrate per unit of volume, higher than the actually in vivo expected, is to compensate the short half-life of 4-hydroperoxicyclophosphamide as well as the lack of the supply-function of current dynamics. 4-hydroperoxicyclophosphamide was the cytostatic agent with the largest range of effectiveness, followed by amethopterine, while the mitotic poisons mitopodozide and VM-26 Sandoz were less effective. The histology and degree of differentiating of the tumors as well as the proliferation rate are not correlated in a distinct manner with sensitivity to cytostatics. Pretreatment with cytostatics of with irradiation revealed no certain influence upon subsequent sensitivity to cytostatics.


[Comparative examination by means of radiograms and computer tomograms on body-like phantoms with equivalent tissues (author's transl)]. A comparative examination of three Alderson phantoms by means of radiograms and computer tomograms shows that there are significant differences between the individual phantoms. Phantom I, for example, is inferior to phantom II because of the bad insertion of the bones into the surrounding plastic material (covered by air bubbles) and the inclusions of air in the soft parts. All phantoms have a rather strong osteoporosis of the skeleton which is most probably due to the production method [1,2]. Furthermore, the average absorption coefficients of the soft tissues show remarkable differences from one phantom to another.


[Biochemical investigations for interpretation of in vivo measurements of 32P-incorporation into irradiated or nonirradiated experimental tumors (author's transl)]. In view of results of extracorporal measurements of the 32 P-incorporation into irradiated or nonirradiated tumors biochemical investigations of the 32P-incorporation have been performed, aiming at comprehension of the meaning and at clarification of the interpretability of these measurements. The results show that irradiation mostly decreases the content of 32P in nucleic acids. In principle, however, the latter is so low as compared to the total content of 32P, especially three hours after 32P-injection, that variations are hardly to be recorded by means of extracorporal measurements, particularly because they are superposed by changes in the 32P-content of other fractions.


Radioprotective effectiveness and toxicity of ATP, AET and serotonin applied individually or simultaneously to mice. III. Radioprotective effects of pair combinations. The work reported was done as part of an intensive investigation on toxic and radioprotective properties of three substances, ATP, AET and serotonin, administered singly or in combination to mice, with a view to identifying optimal dose ratios for cocktails. Male C57BL mice were exposed to 850 R X-rays (LD100/11) following pretreatment with drug pairs at various dose ratios. Thirty-day survival was scored. For ATP-AET, protection increased with the amount of ATP in the combination; this pair was found to be most effective at an ATP-to-AET ratio of 11:1. A similar trend was observed with ATP-Serotonin, though only up to a certain ATP level beyond which no further increase in protective effect were produced; the most favorable ratio was of 24:1. A maximum synergistic action was displayed by the AET-Serotonin pair as compared to the other two pairs; its best ratio was of 4:1. Using probit analysis, a number of PD50 (protectant dose affording 50% survival in lethal irradiation) values were estimated for the three pairs of protective agents.


Predictibility of the stability constant of a radium-cryptate by means of in vivo data from radioactive alkaline earthes. By means of a formula, developed by J. Schubert[9] and A. Catsch, H.J. Heller[3] as well as a relation postulated by A. Catsch[1] the "thermodynamic" stability constant of the Radium (222)-cryptate (KRaRa(222) was calculated from measurements of the total body retention of the total body retention of the radioactive alkaline earthes 85SR, 140Ba and 224Ra and its (222)-cryptates in rats [5-7]. From the same in vivo data a direct lineary relationship between the log of the effectiveness quotient, log EQM(222), and the log of the "thermodynamic" stability log KMM(222) was found graphically. The values from the graph correspond with those of the calculation.


Studies on the effect of leukocyte and erythrocyte extracts on the hemopoetic regeneration of sublethally X-irradiated mice. The cell extracts prepared from leucocytes and erythrocytes of normal rats were applied to C57B1 mice exposed to 300 Rad in 5 injections of 0.5 ml each, during the period of 50-80 hours after irradiation. Significant inhibition in the proliferative compartments of both granulocytic and erythrocytic cells were found in mice submitted to the corresponding cell extract. Our results indicate that cell extracts tested in an animal system demonstrated the same type of inhibitory action as previously reported for the bone marrow cells cultivated in vitro.


Occurrence of lanosterol and lanostenol in seeds of red pepper (Capsicum annuum). Cycloartenol and cycloartanol are the major components of the 4,4-dimethylsterol fraction separated from the seeds of red pepper (Capsicum annuum, Solanaceae). Lanosterol and lanostenol, whose occurrence in higher plants has hitherto been known as extremely rare, are identified in the fraction by gas liquid chromatography, combined gas liquid chromatography-mass spectrometry, and isolation as their epoxides.


Mass spectra of sterically crowded trialkylsilyl ether derivatives of steroids. The electron-impact mass spectra of the title compounds have some important features which give these derivatives certain advantages over the widely studied trimethylsilyl analogues. There is significantly less extensive fragmentation, and abundant ions at (M - t.Bu)+ or (M - i.Pr)+ serve as indicators of molecular weight and should be useful for selected ion monitoring. From various precursors, the ease of elimination of HX2SiOH, via a proposed multi-centre transition state, appears to depend upon conformational and stereochemical factors, as well as the position of the parent silyloxy group, RX2SiO, on the steroid skeleton. This particular fragmentation appears to be a powerful diagnostic method for distinguishing between stereoisomers, being especially useful for differentiation between epimers. In addition, the presence of a 17-silyloxy function promotes a characteristic cleavage of ring B in a skeletally saturated steroid. Elimination of silanol, RX2SiOH, at various stages in the fragmentations of bis-silylated steroids is also an important process, but other familiar features of the spectra of steroid trimethylsilyl ethers, though usually present, are very much suppressed.


Sterically crowded trialkylsilyl ether derivatives for the analysis of steroid metabolites. The applications of sterically crowed trialkyksilyl ether derivatives to the analysis and characterization by thin-layer chromatography, gas chromatography and mass spectrometry, of metabolites of 2alpha, 3alpha-cyclopropano-5alpha-androstan-17beta-ol in the rabbit are described. These derivatives are complementary to the familiar trimethysilyl ether derivatives, but have greater hydrolytic stability (an advantage for TLC), generally give better GC separations, and have characteristic mass spectra. Isomer differentiation by GC and MS is also more readily achieved than via the TMSi ether derivatives. These properties should make SCTASi ethers useful derivatives for studies of steroid metabolism.


Formylated bile acids: improved synthesis, properties, and partial deformylation. Pure performylated bile acids are obtained in quantitative yield by a new formylation procedure. The procedure involves heating the bile acids in 90% formic acid containing catalytic amount of perchloric acid and then adding acetic anhydride slowly until effervescence occurs. Pure performylated bile acids are then isolated simply by diluting the reaction mixture with water. Contrary to what was believed by past investigations, the formyl groups on these compounds are quite stable to various reaction conditions. The stability and ready availability of these compounds make them more suitable candidates than their counterpart--bile acid acetates for use as starting material in various synthetic schemes, such as C-24 labeled bile acids, etc. The partial deformylation of these formates can be effected by using methanolic ammonia, sodium methoxide in methanol, or sodium hydroxide in aqueous acetone. The resultiing 3-hydroxy formyl bile acids are obtained in high yield and are the best starting materials for the synthesis of bile acids with specific modification at 3-hydroxyl group, such as the synthesis of bile acid 3-monosulfates and 3-monoglucuronides.


Effect of thyroid state on estradiol-17beta metabolism in the rabbit. It is well known that the metabolic clearance rate (MCR) of a hormone is influenced highly by the level of its specific binding protein. It was interesting, therefore, to study the metabolism of estradiol-17beta (E2) in an animal model such as the rabbit where there is a lack for a highly specific binding protein for the steroid. The kinetics of the hormone was studied in relation to the thyroid state, namely in rabbits receiving thyroxin or propylthiouracil. In the absence of any significant decrease of the level of the rabbit androgen binding protein (R-ABP), the accelerated MCRE2 and the elevated conversion ratio of estradiol to estrone (CR E2 leads to E1) observed in hyperthyroid rabbits were attributed to the important role of metabolizing enzymes in the liver and/or extrahepatic tissues. In hypothyroid rabbits, while the CR E2 leads to E1 decreased significantly the MCRE2 was not altered.


The in vivo metabolism of progestins. IV. The metabolic clearance rate and plasma binding of 6alpha-methylpregn-4-ene-3, 20-dione in women. [3H]6alpha-methylprogesterone (6MP) was synthesized by selective catalytic tritiation of the delta1-olefinic bond of 6alpha-methylpregna-1,4-diene-3,20-dione. The metabolic clearance rate of 6MP (MCR6MP) was determined in 6 women by the single injection technique. The plasma MCR6MP was 4047 +/- 298 L/day (59 +/- 15 L/day/kg) which was higher than the MCR of progesterone and medroxyprogesterone acetate (6alpha-methyl-17alpha-hydroxy-pregna-4-ene-3,20-dione acetate). The high clearance was not due to binding or metabolism of 6MP by red cells. Although 6MP was bound to CBG with a lower affinity than progesterone, this could not entirely explain the high MCR6MP. When considered with the reports of progesterone and medroxyprogesterone acetate clearance, the present studies suggest that the 6alpha-substitution of progesterone leads to an increased rate of steroid metabolism in women.


Plasma prednisolone concentrations: comparison of radioimmunoassay and competitive protein binding assay. A comparison was made between plasma concentrations of prednisolone measured by both competitive protein binding radioassay (CPB) and radioimmunoassay (RIA) and, with each assay, using a calibration curve generated from individual subject data and from pooling the individual calibration curva data. The plasma samples were obtained from six normal adult male volunteers who were pretreated with dexamethasone to suppress endogenous hydrocortisone and who then ingested 10 mg of prednisolone. Both the standard curve data and the plasma concentrations were evaluated statistically. It was shown that the CPB method has considerably greater precision than the RIA method and could be employed in bioavailability and pharmacokinetic studies of both prednisolone and prednisone. It was also shown that corticosteroid binding globulin cross-reacts considerably less with the major metabolite of prednisolone, 20beta-dihydroprednisolone, than the particular antiserum used in the RIA.


Comparative studies of the effects of fasting on bile salt pool sizes of hamsters and rats. Comparative studies of the effects of fasting on the total bile salt pool sizes of intact and cholecystectomized hamsters and rats were made. Rats, a species which has no gallbladder, are able to maintain the size of their total bile salt pool during 24, 48 and 72 hour fasts by an undetermined effective mechanism. Intact hamsters fasted 24, 48 and 72 hrs maintained and even increased the size of their bile salt pool. Bile salt conservation was effected by storage of the salts in the gallbladder, and to some extent, the small intestine. Cholecystectomized hamsters apparently lack any mechanism to effect bile salt conservation during fasting since their bile salt pool size decreased precipitously during 24 and 48 hr fasts.


Experimental subarachnoid hemorrhage from a middle cerebral artery. Neurologic deficits, intracranial pressures, blood pressures, and pulse rates. Devices to produce experimental subarachnoid hemorrhage (SAH) can be implanted in animals. After SAH is produced by the puncture of a middle cerebral artery (MCA) in awake cats, neurologic deficits develop that are not as severe as those caused by MCA occlusion. Biphasic increases of epidural pressure occur and are related to the extent and distribution of the hemorrhage. Ischemic changes are more severe if the flow of blood through the MCA is interrupted.


Relationships among intracranial pressure, blood pressure, and superficial cerebral vasculature after experimental occlusion of one middle cerebral artery. A cranial window conforming to the contours of the underlying cerebral cortical surface was implanted successfully in 18 cats. Subsequently the left middle cerebral artery (MCA) was occluded inside the sealed cranium and changes in the superficial cortical vasculature were related to measurements of intracranial pressure (ICP), measured extradurally, and to the resulting infarcts. Vascular changes early after MCA occlusion were not predictive of the outcome of the occlusion, except for aggregation of formed elements of the blood in arterioles, which was a bad prognostic sign. Secondary reactive hyperemia was not beneficial; increases of ICP suggested that hyperemia led to increased cerebral edema as well as to swelling.


Automatic end-tidal gas sampling system for non-invasive rCBF measurements. Non-invasive measurements of regional cerebral blood flow (133Xe inhalation or IV injection) require knowledge of the arterial 133Xe concentrations, which is usually estimated from the end-tidal expiration. An automated sampling system is described for measurement of end-tidal 133Xe concentration that can be used in both spontaneously breathing and mechanically ventilated patients. A comparison is made between the automatic sampling system and manual measurements performed on a continuous gas sample.


Cardiac arrhythmias in experimental subarachnoid hemorrhage. Experimental subarachnoid hemorrhage (SAH) in dogs was produced by introducing blood into the subarachnoid space through a catheter connected to an artery of the animal. The intact animals and those with preserved vagi and heart sympathetic innervation, developed arrhythmias with short latencies which correlated with the sudden increase in the intracranial pressure. The animals with sections of both vagi and heart sympathetic innervation, but with an intact spinal cord, developed arrhythmias that were delayed and did not correlate with the changes in intracranial pressure. These arrhythmias were preceded by changes in the QT interval, T wave and ST segment. It was concluded that the arrhythmias could be produced either by direct autonomic discharges to the heart or by increased circulating and tissue catecholamines. The clinical implications of these findings are discussed.


Electrocardiographic changes and myocardial damage in patients with acute cerebrovascular accidents. In 100 consecutive patients with acute cerebrovascular accident, due to cerebral thrombosis in 72, cerebral hemorrhage in 12, embolus in 6, and subarachnoid hemorrhage in 10, there were 90 who had electrocardiographic abnormalities during the first three days after admission, compared to 50% in a control group. The patients with cerebrovascular accident had a 7- to 10-fold higher incidence of ST segment depression, prolonged Q-Tc interval and atrial fibrillation, and a 2- to 4-fold higher incidence of T wave inversion, conduction defects, premature ventricular beats and left ventricular hypetrophy. Patients who died had a 2-, 3- and 5-fold higher incidence of electrocardiographic evidence of recent myocardial infarction, atrial fibrillation and conduction defects than those who survived, but these changes occurred in only 5, 21 and 14% of all patients, and other electrocardiographic changes could not be correlated with mortality. During the first three days after admission 29 patients had elevation of serum enzymes which may be derived from cardiac muscle, particularly CPK, which was increased 6-fold, compared to 2-fold increases in HBDH, GOT, and LDH. Only 5 of these patients had electrocardiographic evidence of recent myocardial infarction. Patients with elevated serum CPK had a 2-fold higher incidence of ST segment depression, T wave inversion, conduction defects and atrial fibrillation than those with normal CPK, and a mortality of 66%, compared to 30%. Of 41 patients who died, 49% had elevated serum CPK, compared to 15% of 59 patients who survived. These differences were significant (P less than 0.01). Serum CPK was more frequently helpful than the electrocardiogram in evaluating the extent of cardiac damage and in predicting mortality. Patients with acute cerebrovascular accident should have repeated evaluation of serum CPK and the ECG, and be monitored for arrhythmias.


Doppler cerebrovascular examination: improved results with refinements in technique. Doppler ultrasonic assessment of extracranial carotid occlusive disease has been modified to decrease the incidence of false positive and negative diagnoses. The technique, which assessed directional flow in the frontal artery and the influence of sequential compression of each temporal, infraorbital, facial and common carotid artery, was performed on 152 vessels visualized by contrast arteriography. Presence or absence of significant (greater than 50%) stenosis or occlusion of the internal carotid artery was identified correctly in 150 vessels (98.7%). Inasmuch as the classic temporal artery compression test only detected 39 of the 61 abnormal Doppler studies (64%), the more complete examination is recommended for screening patients for significant carotid artery obstruction.


Developmental course of hypertension and regional cerebral blood flow in stroke-prone spontaneously hypertensive rats. Regional cerebral blood flow (rCBF) was repeatedly measured by the hydrogen clearance method in the frontal cortex of stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 50 days and thereafter. When SHRSP rats developed severe hypertension (over 200 mg Hg at the age of 60 days) rCBF began to decrease abruptly in the frontal cortex--one of the three predilection sites of stroke in these rats. In contrast, such a reduction in rCBF was not noted in either stroke-resistant spontaneously hypertensive rats (SHRSR) which developed moderate hypertension (under 200 mg Hg), or in Wistar-Kyoto rats (WK) with normal blood pressure (under 15 mm Hg). A similar marked reduction of rCBF with severe hypertension (over 200 mm Hg) was also detected in apoplectic gene-free renal infarction hypertensive rats (RHR) experimentally produced from age-matched WK animals. Blood samples were obtained through an implanted femoral artery canula without disturbing the nonanesthetized SHRSP, SHRSR and WK rats. Arterial blood gas analysis (PaCO2, PaO2 and pH) showed no significant differences at the age of 5 months in any of these rats. Chemical cerbrovascular reactivity, that is, an increase in rCBF in response to CO2 inhalation, showed no significant difference among SHRSP rats from the age of 50 days to 5 months. However, it markedly decreased in SHRSP rats at the age of 9 months and thereafter (the average age of male SHRSP rats which develop stroke is 9 months). The present study showed stroke did not occur in antihypertensive agent-treated SHRSP rats. In these SHRSP rats rCBF did not decrease as long as blood pressure was well-controlled.


Oxidative metabolism in cerebral ischemia. Part 1. Measurement of oxygen extraction slopes of grey and white matter in vivo. Regional oxidative metabolism was studied in vivo. Oxygen availability was monitored from polarographic electrodes in frontal cortical and subcortical tissue. The rate of oxygen extraction in these regions was estimated at frequencies of up to 3 measurements per minute. Transient ischemia of the frontal regions was induced and the resultant decay in the oxygen trace was analyzed kinetically. The oxygen extraction slopes (OES) were steeper in grey than in white matter. They were relatively insensitive to alterations of arterial blood gas concentrations within the physiological range. The slopes were predictably influenced by pharmacologic agents known to alter the rate of oxidative metabolism. Artifacts which may interfere with the OES measurments were considered. This method of estimating regional tissue oxygen extraction may be appropriate for studying aspects of focal CI.


Cerebral arterial smooth muscle contraction by thromboxane A2. The contractile effects of thromboxane A2 (TxA2), a labile arachidonic acid metabolite, were studied in arterial smooth muscle strips. TxA2 was generated upon the addition of 255 nM prostaglandin cyclic endoperoxide H2 to human platelet particles in the muscle bath. Using the isometric contaction produced by 40 mM K+ in isotonic saline as the reference contraction, bovine middle cerebral artery strips contracted to 153 +/- 14% of the reference response while bovine coronary and porcine coronary, renal and common carotid strips contracted to 47 +/- 3, 26 +/- 5, 43 +/- 2 and 2 +/- 1% of reference, respectively. The cerebral artery response to the TxA2 generating system was as great as the maximum response to prostaglandin F2alpha and two times the maximum response to 5-hydroxytryptamine. Because TxA2 is formed by brain tissue and released from aggregating platelets, it may be important in the pathogenesis of spasm associated with injured brain tissue or pathologic changes leading to platelet aggregation.


Relationship of transient ischemic attacks and angiographically demonstrable lesions of carotid artery. Eighty-eight percent of arteries in patients with amaurosis fugax or hemispheric transient ischemic attacks had angiographically demonstrable lesions at the carotid bifurcation. Eighty-one percent had stenoses or occlusions at the carotid bifurcation; 7 percent had ulcerative lesions without stenoses at this site. Forty-nine percent of arteries in these patients demonstrated ulcerative lesions with or without stenosis at the carotid bifurcation. There was no significant difference in the incidence or types of ulcerations between those patients with amaurosis fugax and those with hemispheric transient ischemic attacks. Eighty-eight percent of arteries examined in this series were amenable to surgical reconstruction. Amaurosis fugax and hemispheric transient ischemic attacks were of equal value in predicting the possibility of a surgically treatable lesion at the carotid bifurcation.


Evoked potential changes during brain retraction in dogs. Brain retraction and induced hypotension are surgical adjuncts capable of compromising cerebral blood flow. To evaluate their effects upon brain function, cortical evoked potentials, neurological status and cortical histological changes were determined as a function of graded levels of brain retractor and systemic perfusion pressure in the dog. Somatosensory evoked potentials recorded from the site of application of brain retraction showed a decrement as a function of both the amount of retraction pressure and the systemic perfusion pressure. An electrode distant from the retractor site showed similar, though reduced and more variable changes in amplitude. For higher levels of brain retractor pressure, induced hypotension to 50 mm Hg systemic perfusion pressure produced greater reductions in evoked potentials than in normotensive subjects. It was demonstrated that a reduction of 50% of the evoked potential amplitude after sixty minutes brain retraction signaled, with high probability, the occurrence of postoperative sensory and/or motor deficits and cortical histopathology. It was concluded that cortical evoked potentials represent a reliable indicator of the functional effects produced by applied cortical retraction pressure at several levels of systemic perfusion pressure. It was suggested that the recording of evoked potentials would prove most useful during neurosurgical procedures employing induced hypotension and brain retraction.


[Modeling the cell cycle of complex populations]. A model of cell cycle kinetics of complex populations is developed, by using systems of difference equations, and simulated on the computer. This model provides theoretical curves of labeled mitoses (PLM) percentage, labeling index and grain count histograms for different time intervals after 3H-thymidine administration. The PLM curve corresponding to a mixed population is a weighed sum of PLMs for populations, comprising the mixture, the weights being determined by parameters of populations. The model appeared to give a good agreement with the PLM curves obtained elsewhere.


[Cell population mechanisms of inhibition of erythropoiesis in polycythemia]. The ciliary activity of Ctenophore bolinopsis is inhibited by decreasing concentration of Mg2+ and increasing concentration of Ca2+ in the medium. The same changes in Mg2+ and Ca2+ concentration trigger muscle contractions and bioluminescence. Co2+ arrests the cilia beating in the rectangular position. An increase in Mg2+ concentration or decrease in Ca2+ concentration switch off the nervous inhibitory mechanisms of ciliary activity, suppress muscle contractions and bioluminescence. Ni2+ produces a similar effect, but the ciliary heating is only slightly accelerated, by the contrast to the effect of increased Mg2+ concentration. A Cl-free medium Mn2+ and tetrodotoxin in commonly used concentrations are of no effect on the systems studied. Experiments involving changes in K+ concentrations and administration of tetraethylammonium suggest that the resting potential in the examined cells may be due to K+ as the most permeant ion, and that K+-channels in the cell membrane may be voltage--controlled. The proposal about "biionic" (Ca2+/Mg2+) bioelectric control of a number of intracellular reactions is discussed.


[Ultrastructure of rat cerebral cortex neurons at different levels of motor activity]. The reaction of neurons in rat motor cortex during the intensive motor activity and fatigue caused by swimming was investigated with the electron microscope. In both the cases the nuclear envelope in the neuron perikaryon was sharply enlarged resulting in the appearance of deep invaginations; the nucleolus displaced towards the nuclear envelope. Components of the endoplasmic reticulum and Golgi complex increase in size and number, ribosomes become more numerous, the cytoplasm getting denser. During fatigue the above changes appear more pronounced in addition to mitochondrial swelling, the matrix becomes less dense and cristae less numerous. These changes suggest the intensification of metabolitic activity of the cortical neurons during both the intensive motor activity and fatigue.


[Antimutagenic activity of tryptophan].

[Antimutagenic activity of tryptophan]. Antimutagenic activity of tryptophan in concentrations of 2-10(-3), 1-10(-2), and 5-10(-2) M was found in Allium cepa L. seedlings. These concentrations of tryptophan inhibit cell mitotic activity. By decreasing the frequency of spontaneous mutations and suppressing the mitotic activity of cells, tryptophan affects various functions of cells. The spectrum of chromosome mutations in tryptophan-treated seedlings does not differ from that observed under natural conditions.


[Use of Allium fistulosum L. seeds as a preliminary test for studying mutagenic factors in the environment (drugs)]. The mutagenic activity was studied for the following 14 psychotropic drugs: aminazinum, fluphenazinum-decanoate, thioproperazinum, reserpinum, chlordiazepoxidum, diazepam, oxazepam, trioxazin, tavor, dipheninum, hexamidinum, benzonalum, carbamazepinum, ethosuximidium. It is shown that carbamazepinum, benzonalum, chlordiazepoxidum considerably increase the frequency of chromosome aberrations in the Allium fistulosum L. cells. These drugs were selected for studying their mutagenic activity on the laboratory animals.


[Electron microscopic study of rat hepatocytes following exposure to dicyclohexylamine nitrite and an oil-soluble salt of cyclohexylamine]. Ultrastructural changes were studied in the rat liver under the effect of dicyclohexylamine nitrite and oil-soluble salt of cyclohexylamine in doses of 1/10 LD50. Both substances are stated to cause damages in the structure of hepatocytes even after three days of exposure. Dicyclohexylamine nitrite shows a more pronounced effect displayed in developed dystrophic changes of cytoplasmic organelles and in the presence of osmiophil bodies.


Influence of autologous serum on in vitro reactivity of peripheral lymphocytes of  patients with breast cancer. The influence of autologous serum on DNA synthesis and phytohemagglutinin (PHA) or pokeweed mitogen (PWM) stimulation of peripheral blood lymphocytes from mammary tumor-bearing women has been studied. Blood samples were collected from patients at the 4 stages of the TNM classification who had not undergone any therapeutic treatment. Lymphocyte functions were significantly reduced only in patients with the largest tumors and in the latest stage of disease. Autologous cancer sera inhibited spontaneous DNA synthesis of lymphocytes and did not inhibit lymphocyte stimulation by mitogens. It is possible that unrecognized inhibiting and stimulating factors, possibly acting in synergism with mitogens, are present in mammary cancer sera.


Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice. The interaction between cyclophosphamide (CPA) and phenobarbital (PB) was investigated in B6D2F1 mice, checking both the antileukemic and immunosuppressive activity together with the serum levels of CPA and its metabolites. A reduced cytotoxic activity of CPA has been observed when PB is given for 2 days before CPA and an interval of at least 6 hours elapses between the last treatment of PB and the administration of CPA. On the contrary, when PB is given simultaneously with CPA for 2 or 4 consecutive days, an increased antileukemic activity of CPA occurs. In the experimental condition where PB decreases the activity of CPA, serum levels of CPA, assayed by means of a new specific gas-chromatographic method, and of its NBP-alkylating metabolites, indicate that this effect may be explained on a pure pharmacokinetic basis. However, for the situation where an increased effect of CPA was observed under the influence of PB, pharmacokinetic data did not provide a clear explanation.


Effects of high doses of peptichemio upon the humoral response to sheep erythrocytes and delayed hypersensitivity reactions to oxazolone in CBA mice. A study has been carried out on the immunosuppressive activity of high doses of peptichemio (PTC) in CBA mice. Humoral response to sheep erythrocytes, delayed hypersensitivity to oxazolone, and cellular proliferation in lymph nodes and spleen of animals sensitized with oxazolone have been investigated. The results demonstrated that PTC had a definite immunosuppressive action, as shown by the inhibition of primary response to inoculation of sheep erythrocytes, by depression of delayed hypersensitivity to oxazolone, and by marked inhibition of 125IUdr incorporation in lymph nodes of sensitized animals. It is suggested that the inhibitory action is mediated by an effect on actively proliferating B or T lymphoid cells, although involvement of macrophages cannot be ruled out.


Interferon in breast cancer.

Interferon in breast cancer. The interferon production ability by leukocytes in vitro from 37 patients with mammary cancer was studied. The leukocytes were derived from patients between 27 and 80 years of age, 6 months and up to 28 years after removal of the primary tumor. The interferon titer of 34/37 human breast cancer leukocytes was 2-8 times lower than that of 35 normal donor leukocytes and 3 non-neoplastic diseases. No correlation between interferon titers, the patient's age, and the histologic tumor features was observed; however, interferon production was observed to return to normal in those patients who had a long remission period or whose tumors were locally confined. Interferon response of patients under different therapy was modified: radiotherapy affected interferon production more severely than chemotherapy. A tendency for association between the skin DNCB test and interferon response was found. An inverse correlation was observed between interferon titers and the PHA-induced transformation index.


Parotid gland tumors in infants and children. Eleven cases of parotid tumors in children under 16 years of age are considered. The series accounts for 1.6% of 657 cases of parotid tumor of all ages observed during the period 1930-1975 and consists of 6 mixed tumors, 2 mucoepidermoid tumors, 2 angiomas, and 1 benign lymphoepithelial lesion. All the patients underwent surgical treatment, 6 radical and 5 limited. The results of treatment point out that mixed tumors require radical parotidectomy. The attitude towards pediatric parotid tumors is dicussed.


Serum copper and ceruloplasmin levels in patients with neoplasias localized in the stomach, large intestine or lung. Serum copper and ceruloplasmin levels were determined in patients with solid neoplasias in different sites (stomach, large intestine, lung). Statistical analysis showed that serum copper levels increased significantly in all the forms studied. The serum ceruloplasmin level, on the contrary, was high in gastric and pulmonary cancer, while in tumors localised in the large intestine the increase was not significant. In 58 cases, there was a correlation between copper and ceruloplasmin levels in the same subject; this correlation proved significant solely in gastric forms. Moreover, statistical analysis of the two parameters in question did not reveal any significant differences between localized and metastasized in forms.


A quantitative test for chemosensitivity of short-term cultures of human lymphomas. An in vitro chemosensitivity test is described for the quantitative determination of the interference of antitumoral drugs on nucleic acid metabolism in short-term cultures of non-Hodgkin's malignant lymphomas. Preliminary biochemical studies have defined the optimal culture conditions and have guaranteed the reliability and the reproducibility of the test. Our results for adriamycin and prednisone are in agreement with those obtained on experimental systems with other techniques.


A combination of cyclophosphamide, methotrexate, vincristine and VP 16-213 (NSC 141 540) in the treatment of bronchogenic carcinoma. Thirty patients with bronchogenic carcinoma were treated with an 8-week induction therapy consisting of cyclophosphamide, methotrexate, vincristine and VP 16-213 (NSC 141 540). Those who achieved objective remission of tumor stabilization were then placed on an intermittent treatment schedule with the same drugs. Of the 30 patients, 17 had an objective response, 5 remained without change, and 8 progressed. Responses were more frequent among anaplastic (13/19) than epidermoid or adenocarcinoma (4/11). The toxicity consisted mainly of leucopenia, thrombopenia, alopecia, nausea and vomiting. The implications of these findings in the planning of further chemotherapeutic programs are discussed.


Lymphographic evaluation in bone and soft tissue sarcomas. A group of 79 patients with soft tissue sarcomas and 46 with primary malignant bone tumors underwent lymphangiography as part of the initial diagnostic workup. In the group of soft tissue sarcomas, the overall incidence of metastases was 22 of 79 (28%). According to the site of origin, the highest incidence was found in tumors originating from the buttocks (57%), followed by those from the inferior limbs (31%). Considering the histology, the incidence ranges from 50% in anaplastic sarcoma, to 43% in rhabdomyosarcoma, to 23% for liposarcoma and fibrosarcoma. The incidence of lymphographically proven metastases in bone tumors was 8 to 46 (17%), with 1 out of 4 in reticulum cell sarcoma, 1/1 in chordoma, and 22% in Ewing's sarcoma. A radiographic/histologic correlation on the lymph nodes was obtained in 19/79 (24%) soft tissue sarcomas and in 4/46 (9%) bone tumors. In the 12 radiographically negative and 11 radiographically positive cases, this correlation was always correct. The results of this study suggest a larger use of lymphography in these tumors.


A statistical approach to detection of the primary cancer based on the site of neck lymph node metastases. Preoperative differential diagnosis of a swelling in the neck is mandatory for a good therapeutic planning. Indiscriminate biopsy as first approach is to be disregarded, since it can compromise the result of a radical neck dissection in cases where a metastasis of epidermoid cancer is histologically recognized. A cervical biopsy is not to be performed until a complete HNT examination (including the thyroid and major salivary glands) has excluded the presence of a primary tumor in these regions. Since every localization of the head and neck malignancies shows rather fixed patterns in its lymphatic spreading, a correlation between site of T and particular localizations of N within the neck can be found. The knowledge of the probabilities that an adenopathy in a given region of the neck correlates with a primary tumor located in a given site of the body could strongly aid the physician in detecting the latter, following a rational statistically based approach. This study was performed applying Bayes theorem for probability calculus to the maps of distribution of metastases of tumors of different site in 3,700 patients who were taken into National Cancer Institute of Milan during 7 consecutive years. The results are gathered in tables and text-figures showing the great significance of some correlations, who become more evident when the adenopathies are multiple, but who usefully direct the physician also when the adenopathy is only one.


Hyperthermic isolation-perfusion with melphalan, a preliminary appraisal of local and general effects in malignant melanoma. Ten hyperthermic isolation-perfusions with melphalan were performed for invasive malignant malenoma of the limbs. Four cases at stage II and with in transit metastases (up to 15 cm in diameter) had a complete regression. However, no improvement of survival was noticed: 4 out of 5 stage II patients who died, within 1 year after perfusion, developed a generalized disease. Systemic chemotherapy was administered in 3 patients after perfusion, but they died from distant metastases. The need for an adequate adjuvant treatment added to isolation perfusion is discussed.


Experience with BCG adjuvant immunotherapy in stage II malignant melanoma. Three years experience with post operative BCG adjuvant immunotherapy in stage II malignant melanoma is reported. Compared to a historical control group (35 cases), 23 melanoma patients showed a significantly improved remission duration and survival rate. It appears that patients with weak initial BCG reactions, which become gradually positive after several immunizations, get more benefit from the adjuvant immunotherapy than do patients with strongly positive initial BCG reactions.


Regional chemotherapy of maxillofacial malignant melanoma with intracarotid artery infusion of DTIC. Six intracarotid artery infusions of DTIC were performed in 4 patients with invasive malignant melanoma of the maxillo-facial region. A total dose of 3.5 to 7 g was well tolerated. Only 1 patient who received 9.5 g in 25 days developed a reversible bone marrow depletion. Two out of the 4 patients presented a transient 50% tumor surface regression, but no response was seen after the second infusion. Of the 2 remaining patients, 1 had no measurable effect and 1 experienced tumor progression.


[Effect of deuteration on some IR-spectral characteristics of gelatin]. The IR-spectra of normal and deuterated gelatin samples were studied. The 3300 cm-1 band is determined by the valence vibrations of the peptid bond NH-groups, OH-groups of oxyproline and structural water. The 1280-1220 cm-1 bands cannot be intepreted for gelatin as amide III; their appearance is caused by the skeleton vibrations. The 1460 cm-1 band is not Amide II in gelatin, it is associated with the deformation vibrations in free methyl groups of the amino acid residues. The effect of OH-groups of hydration water forming the intramolecular hydrogen bond is displayed by 1670 cm-1 band. Disappearance of the 1560 and 1530 cm-1 bands with deuterating and appearance of the 1580 cm-1 band may evidence for a structural transition of the gelatin molecule from one conformation to another, is more ordered, conformation.


[Application of ion-selective electrodes for determining ion concentration in blood of irradiated rabbits]. Concentration of potassium and sodium ions as well as chlorides in rabbit blood serum was determined by applying the direct potentiometric method using the ion-selective electrodes. The techniques on calibration of the applied ion-selective electrodes are described and comparative data are presented of determining the concentration of potassium and sodium by the potentiometric method and that of flame photometry and of chlorides by the potentiometric and chemical methods. By high-specific ion-selective electrodes (glass for Na+, membrane one for Cl- and valinemycinic for R+) the character of ionic disturbances is established in the blood serum of rabbits irradiated with a dose of 2000 R. The concentration of potassium ions decreases 15-18 degrees min after irradiation. The concentration of sodium ions and chlorides is not changed noticeably. The concentration of calcium determined by the method of flame photometry decreases after irradiation within a range of 30 min-72h. The found changes may be explained by the damaging effect of radiation on the structure and function of the cell membranes.


[Content of collagen fractions and synthesis of collagen in lung tissues of rats of various ages]. The content of soluble fractions and biosynthesis intensity of collagen were studied by means of 3H-proline incorporation into the lung tissues of different-age rats. The method with incorporation of a radioactive label is shown to detect more clearly the age peculiarities in collagen metabolism. The most considerable decrease in the intensity of 3H-proline incorporation into lung collagen is observed during the first four months of the rat life.


[Significance of adrenal hormones in brain energy metabolism]. Intensity of glycolysis was studied under conditions of immobilization stress and adrenalectomy as well as with administration of adrenaline and hydrocortisone. The processes of aerobic glycolysis, activity of enzymes of the tricarboxylic acid cycle and mitochondria respiratory chain, content of total, free and protein-bound glycogen, glucose-I-phosphate, glucose-6-phosphate, pyruvate, alpha-ketoglutarate, cytrate and macroergs in the brain are shown to depend on the level of adrenal hormones producing a multilateral effect on a series of energy metabolism links.


[Acetylcholinesterase of subcellular structures of rabbit brain in ontogeny]. Subcellular fractions of the cerebral hemispheres of rabbits of different age groups are isolated by differential centrifugation in the sucrose gradient. The acetylcholinesterase activity of the fractions is also determined. It is found that in the postnatal period the specific activity of the enzyme increases in synaptosomes and pure mitochondria, is unchanged in the initial homogenate and in the subfraction of mieline fragments. The relative specific activity of acetylcholinesterase is unchanged in mitochondria, increases sharply in synamptosomes and decreases in the subfraction of myeline fragments. Changes in the specific and relative specific activity of acetylcholinesterase in the subcellular fractions of the developing brain are concluded to reflect the degree of functional maturation of cholinergic structures responsible for conducting the nervous impulse.


[Effect of tetrachloromethane on alpha-ketoglutarate dehydrogenase and succinate dehydrogenase activity in mitochondria of rat liver under conditions of administration of polycyclic hydrocarbons]. The activity of the mitochondria internal membrane ensymes alpha-ketoglutarate dehydrogenase and succinate dehydrogenase was studied after rats poisoning with CCl4. It is established that the activity of these enzymes lowers considerably under effect of CCl4, which is more pronounced for alpha-ketoglutarate dehydrogenase. The pretreatment of animals with inducer of microsomal oxidases intensifies the damaging effect of CCl4 on the internal membranes of mitochondria and decreases the LD50 value for CCL4. Administration of actinomycin D simultaneously with polycyclic hydrocarbons prevents intensification of the CCl4 hepatotoxic effect caused by 3-methylcholanthrene and dibenz (a, h) anthracene.


[Dependence of vitamin C content in animal tissues on the dose of UV radiation]. The content of vitamin C in tissues was determined for animals synthetizing (rabbits) and nonsynthetizing (guinea pigs) it with UV radiation. Significant doses of radiation cause a considerable decrease in the content of vitamin C in blood of both animal species. In the adrenal, liver, spleen, lung, small intestine, kidney, brain tissues and vitamin C content decreases in animals nonsynthetizing the vitamin and, vice versa, it rises in the vitamin-synthetizing animals. After irradiation with small doses the vitamin C content in blood and tissues of animals nonsynthetizing it lowers but not below the normal level. Additional administration of 100 mg of ascorbic acid (under conditions of sufficient supply of vitamin C with food) does not prevent a decrease in the content of vitamin C in blood of the animals irradiated with significant UV doses. An opinion is advanced as to necessity of vitamin C rationing taking into account "the UV climate" of the area and dose of radiation from the artifical sources.


[Low temperature and cryoprotectant effect on oxygen uptake in rat kidney cortex homogenates]. Respiration and oxidative phosphorylation of the rat kidney cortex mitochondria are studied as affected by low temperatures and cryoprotectants. There is no change in respiration in state 2 during freezing and thawing of the rat kidney cortex slices both in case of using the succinate oxidation substrate and alpha-ketoglutarate. Respiration in state 3 is inhibited in the medium with alpha-ketoglutarate during freezing under protection of polyethylene oxide-100 (PEO-100) and glycerol, and does not significantly change in case of using dimethyl sulphoxide (DMSO). The effectiveness of cryoprotectants used in the experiments reduces in the following sequence: DMSO--glycerol--PEO-100. Preservation of the main mitochondria function, ATP synthesis, is shown to be possible for the kidney cortex slices exposed to freezing and thawing.


[Effect of oxygen, water and hydrophobic medium in model reactions of thiamine pyrophosphate]. Oxygen and water are inhibitors of acyloin and benzoin condensations. An intermediate paramagnetic compund is formed in the benzoin condensation catalyzed with 3-benzyl-4-methyl thiazolium chloride, 3,4-dimethyl thiazolium iodide, 3-benzyl-4,5-dimethyl thiazolium chloride, 3-methyl-4-phenyl thiazolium perchlorate and 3-methyl-4,5-diphenyl thiazolium perchlorate. The formation of benzoin in dimethyl sulphoxide, when the air oxygen is absent, is an irreversible reaction. The presence of hydrophobic solvent in the reaction medium provides more favourable conditions for benzoin condensation proceeding. The reaction mechanism is suggested.


[Effect of estradiol on content of monoamines and acetylcholine in rat hypothalamus]. Administration of estradiol-benzoate in a dose of 0.5 Mg for 4 days causes a twice increase in the content of acetylcholine in hypothalamus of impuberal female rats and statistically significant decrease in the content of GABA. The level of serotonin, dopamine, noradrenaline and histamine in the hypothalamus of the animals is not affected by 0.5 Mg of estradiol-benzoate. Administration of prolactin against a background of estradiol--benzoate normalizes the content of GABA and produces a statistically significantly drop in the level of acetylcholine in the hypothalamus. A conclusion is drawn that acetylcholine and GABA are involved into regulation of prolactin secretion in rats.


[Effect of cryoprotectants on protein-synthesizing activity of cell-free system from rat liver]. The protein-synthetizing activity in postmitochondrial supernatant (S15) was studied as affected by ethylene glycol, PEG-400, PEG-4000, DMSO, ethanol, methanol, and glycerol. It is found that cryoprotectants inhibit 14C-leucine incorporation in the presence of physiological concentrations of Mg2+ (5 mM) in the cell-free system. All cryoprotectants, exept of glycerol, shift the maximum of 14C-leucine incorporation towards lower Mg2+ concentrations in the cell-free system.


[Changes in protein spectrum of cattle blood serum with lympholeukosis]. The protein spectrum of blood serum was studied in healthy cows and those suffering from leucosis. The total amount of protein at the early stages of the disease is established to be unchanged. But with lympholeucosis the content of the globulin fraction increases with a simultaneous decrease in the amount of albumins within 20%. The globulin fraction content rises due to immunoglobulin G. The albumin: globulins coefficient is 0.56 for animals with leucosis and 0.84 for the healthy ones. A problem on possible qualitative changes in this fraction similar to those occurring with other forms of malignant growth is under discussion.


[Postnatal changes of gamma-aminobutryric acid in rat brain with acute benzene poisoning]. Benzole vapours cause a decrease in the content of glutamic acid in the motor cortex, cerebellum, pons varolii and spinal cord of the rat brain at different stages of ontogeny. The content of GABA increases in all the areas during ontogeny with benzole intoxication. The glutamate decarboxylase activity increasing in all brain areas in different periods of postnatal development rises after the benzole action. The activity of GABA transamination enzyme in the brain motor cortex under the benzole effect is not changed in newborns and three-month rats, in 10- and 21-days rats it decreases, in 12- and 24-months animals it increases. In the cerebellum, pons varolii and spinal cord the activity of this enzyme rises in newborns, three- 12- and 24-months rats and lowers in 10- and 21-day ones. The rise in the level of GABA and activity of the enzymes of its metabolism in the different brain areas under the benzole effect is considered as an adaptation reaction of the nerve cells.


[Effect of carboxylation reactions stimulation on intensity of 14CO2 fixation in rabbits with posthemorrhage anemia and on repairing of blood components in human anemia]. The repair processes with posthemorrhage anemia were studied in experiment and clinics as affected by the preparation (sodium bicarbonate and magnesium, manganese and zinc sulphates in a ratio of 25:5:0.1:0.1) which stimulates the carboxylation reactions in the organism. Stimulation of the carboxylation reactions in the rabbits with experimental posthemorrhage anemia increases the intensity of 14CO2 carbon transformation of organic compounds in the tricarboxylic cycle, intensifies 14C incorporation into the liver, kidneys, spleen and marrow proteins as well as into serum albumin and globulins. Under clinical conditions stimulation of CO2 fixation with the preparation favours an intensified formation of the red series cells and biosynthesis of hemoglobin and serum proteins as well as the repair of their disturbed balance in patients with posthemorrhage anemia. The content of magnesium in blood plasma normalizes.


A high resolution ultrasonic microscope. The construction and imaging capabilities of a scanning high resolution ultrasonic microscope are considered in this paper. Theoretical expressions for the resolution limits of the microscope and some of the most important properties of the ultrasonic lenses are given. Ultrasonic through-transmission and back-scattering images of different objects are presented and a quasi-three-dimensional display mode is introdued. A resolution of about 4 micron is demonstrated at 300 MHZ by the present ultrasonic microscope.


Ultrasound grey scale display on storage oscilloscope system. A grey-scale display system for ultrasound contact B-scanning has been developed that produces six shades of grey on a high resolution storage oscilloscope. The grey shades are displayed by varying the density distribution of dots of a constant intensity. The system design and clinical results are presented. Advantages of our system are: 1. the non-degraded image is immediately displayed as the scan is performed. 2. the writing speed is faster than most scan converter tube systems son that many closely spaced scans can be rapidly performed in order to improve visualization of small anatomic structures, and 3. images comparable to those of scan converter display systems are produced at a significantly lower equipment cost.


Tumour detection by ultrasonic Doppler blood-flow signals. Ultrasonic Doppler blood-flow signals which seem to be associated with malignant tumour neovascularization have been detected in the female breast. No such signals have been detected from cysts. This discovery may lead to the development of a highspeed ultrasonic Doppler scanner which might make breast screening for cancer practicable.


[Conductometry in determining measurements of urine electrolyte concentration (author's transl)]. 1. Na+ concentration, measured by the flame photometer, cryoscopic osmolality, and the specific electrolyte conductivity of urine show a close statistical correlation if only small amounts of a molecular disperse solution are dissolved in the urine. 2. Since conductance of a fluid is an expression of its ion concentration, better relationships exist between Na+ concentration and conductivity than between Na+ concentration and osmolality. 3. In the presence of large amounts of glucose in the urine, osmolality no longer represents the electrolyte content, and therefore no longer serves as a parameter of renal concentration power. On the other hand, the close correlation between conductance and Na+ concentration remains. 4. Conductometry supplements osmometry significantly by its selective capacity to determine electrolyte components in the urine. 5. Owing to the short time spent on the method and small errors in technique, it remains debatable whether conductometry is preferable to osmometry in normal cases for determining measurements in concentration in the urine.


[Regional lymph node metastases in renal cell cancer. Morphologic findings and clinical consequences (authors transl)]. With a uniform pathohistological technique of investigation the frequency of histological verified lymph node metastases in tumor nephrectomy depends on the surgical approach. Lymph node metastases were seen twice (6%) in 33 cases of lumbar nephrectomy, 22 times (17%) in 132 cases of abdomino-paracolic operations without systematic lymphadenectomy, 11 times (37%) in 30 abdomino-transplical nephrectomies with systematic lymphadenectomy. Primarily, one can expect lymph node metastases in case of infiltration of capsula adiposa, macroscopic invasion of veins, histologic grade 3 of malignancy, and/or if the tumor exceeds a size of 10 cm. Metastases are also possible in not enlarged and macroscopic normal lymph nodes. Without systematic dissection of the regional abdominal lymph nodes unknown regional lymph node metastases are likely to remain. Therefore, the treatment of choice in renal cell cancer is abdominal transplical nephrectomy with systematic lymphadenomectomy.


[Pain relief by means of continuous epidural analgesia after retroperitoneal lymph node dissection (author's transl)]. A retrospective study compares the effectiveness of postoperative epidural analgesia with conventional analgetic medication in cases of retroperitoneal lymph node dissection. Epidural analgesia is noted for its reduced need for additional medication and for its lower incidence of complications.


[Coral calculus in the cystic kidney (author's transl)]. A clinical case is described featuring bilateral lithiasis of the renal pelvis and calices in conjunction with cystic kidney in a female patient. Progression was shown by tumor enhancement in the lower abdomen, a distension of the concretions in pyelogram, and an increment of creatine in the serum. In this case there was no indication for surgery.


[Oxalate urolithiasis--an occupational disease? (author's transl)]. A patient working as a stove-fitter suffers from calciumoxalate urolithiasis. The exploration of his typical occupation and the special investigation of lithogenic factors in urine and serum points to deterioration of oxalate urolithiasis.


[Experiences with lavage cytology from renal pelvis and ureter (author's transl)]. In 41 cases of roentgenologic filling defects in renal pelvis and ureter, which could not be determined exactly preoperatively, we could confirm the diagnostic value of cytology from washings of renal pelvis and ureter (lavage cytology), especially in preoperative diagnosis of carcinoma of renal pelvis and ureter. Ten of fourteen tumors (71%) were detected by this method. The diagnostic reliability increased with tumor-stage and was more accurate than the normal exfoliative urinary cytology. In five cases of hypernephromas invading the renal pelvis lavage cytology was not successful and we had obtained only false negative results. In roentgenologic filling defects that were not tumor-induced especially uric acid stones, inflammatory processes, blood clots and renal cysts, we had no false positive results. Our findings are discussed together with the literature.


[Balloon ureter catheter for temporary endo-drainage (author's transl)]. A new balloon ureter catheter (catheter 7-French, balloon 9-French) is described. It offers important advantages over conventional catheters for temporary endo-drainage in the treatment of urinary obstruction as well as renal and ureteral fistulas. An angled whistle-tipped catheter facilitates placement. Sufficiently large drainage openings above and below the balloon and an additional outflow lumen prevent obstructions. The special catheter is held in an optimal position inside the balloon underneath the whistle tip. Thus, no further fixation is necessary, and the patients need not be confined to bed.


[Septic shock in the uroseptic patient. I. General and specific pathomechanisms of the septic shock (author's transl)]. Failure of microcirculation in septic shock is due to the generalized release of catecholamins following a fall in cardiac output by the activity of bacterial toxin. The failure of the microcirculation can be defined as 1. a failure of the distribution of the tissue perfusion, and 2. a decrease of capillary flow due to obstructed inflow, reduced capillary flow passage and obstructed outflow. Bloodviscosity increases because of fluid sequestration, aggregation of rbc's and decrease in velocity of the blood flow. All this results in a dispariaty of oxygen consumption and availability to the tissue. The characteristics of specific organ disturbances in shock go along with the distribution of the alpha-receptors in each organ, the specific physiological function and architecture of the organ as well as previous diseases of the organ.


[Septic shock in the urologic patient. II. Pathomechanisms of hemostatic disorders (author's transl)]. In urosepsis endotoxins usually deriving from gram-negative bacteria can initiate primary disturbances of hemostasis by activation of coagulation up to clinically manifest consumption coagulopathy. The reaction is triggered by an endotoxin induced alteration of granulocytes, endothelial cells, and platelets, thereby releasing procoagulant activities that possibly cause diffuse intravascular coagulation with impairment of vital organs. Additional negative effects on hemostasis can be caused by secondary hyperfibrino(geno)lysis. Secondary disturbances of hemostasis occur in urosepsis as a consequence of an impairment of liver (hypoproduction of coagulation factors, decrease of the clearance of activated coagulation factors) and kidney function (thrombocytopathy by uremic toxins). Disturbances of hemostasis induced by the treatment of urosepsis are the K-hypovitaminosis in parenteral feeding accompanied by antibiotics affecting the intestinal bacterial growth and the alteration of platelet function and fibrin formation by carbenicillin.


Five-hour renal functional evaluation.

Five-hour renal functional evaluation. Children with urogenital disease frequently require evaluation of glomerular and tubular functions. Herein is presented a practical method of performing glomerular and tubular functional studies requiring short time periods and utilizing readily availabe laboratory techniques.


Urinalysis in patients on chronic hemodialysis. To determine what urinalysis findings are normal in patients maintained on chronic hemodialysis, we have studied the urine in 25 such patients. In end stage renal disease correlation with the original disease is lost, and urine characteristically contains many white blood cells and frequent white blood cell casts; microscopic hematuria is unusual even in patients whose original disease was a proliferative nephritis.


Vesicoureteric reflux and ureterovesical obstruction. The unusual combination of reflux and obstruction as seen in 8 of a series of 40 unduplicated ureters reimplanted for reflux is presented, with particular reference to the mechanical obstructing factors which can be demonstrated. These involve the extravesical rather than the intravesical ureter so that separate pathologic mechanisms for obstruction and reflux must be postulated. This unusual obstruction/reflux combination appears to be more common than is generally recognized, and the need for its early recognition and surgical correction contrasts with the less urgent indications for operative intervention in ureteric reflux alone.


Traumatic ureteral injuries with delayed recognition. Review of ureteral injuries treated in the past ten years at the Los Angeles County-University of Souther California Medical Center revealed 9 cases of traumatic injury which escaped immediate recognition. These patients were found to have a poor prognosis with a higher incidence of nephrectomy when compared with those patients with immediate diagnosis and treatment.


Experimental bladder substitution using biodegradable graft of natural tissue. A controlled experimental study has been performed using a biodegradable graft of natural tissue to achieve vesical augmentation. The graft is progressively reabsorbed while normal capacity is maintained by concomitant regeneration of the layers of the bladder remnant. No significant complications were encountered, and the graft was equally successful when applied either to a histologically normal bladder or to a pathologic bladder of intramural fibrosis. This material is potentially ideal for clinical bladder substitution in humans.


Cystitis glandularis.

Cystitis glandularis. We present 12 cases of cystitis glandularis which fall into two distinct groups, one characterized by hematuria and the other by urinary tract infection. We can produce no clinical evidence that this disease is premalignant, but emphasize the necessity of histology to exclude malignancy since, macroscopically, the condition is indistinguishable from mitotic changes. We also describe the association of cystitis glandularis and pelvic lipomatosis.


Dynamic activity of bladder neck and external sphincter in ejaculation. The bladder neck shows a typical electromyographic pattern in ejaculation. It consists of periods of heightened activity rhythmically alternating with intervals of reduced activity signifying muscular contraction and relaxation. This behavior of the bladder neck is confined to its ventral part. Concurrently, the external sphincter shows a short period of increased activity before the typical rhythmical pattern which corresponds to that of the ventral bladder neck.


Pheochromocytoma: recent experience with detection and management. Our experiences spanning a ten-year period have been reviewed with regard to pheochromocytoma. During this period 1,890 metanephrine excretion levels were performed; 91 of these were elevated. An over-all incidence of 1.9 per cent false positive studies was found. Factors contributing to the false positive studies are discussed. Fourteen patients had 15 pheochromocytomas resected. The presenting features, diagnosis, localization, preoperative and operative management, as well as the results are presented.


Acute scrotal swelling in Henoch-Schönlein syndrome. A review of the literature regarding scrotal swelling in Henoch-Schönlein purpura is compared with our own experience at the Mayo Clinic over the previous ten years. Of 59 boys seen with Henoch-Schönlein purpura, 9 were noted to have scrotal swelling, and in 4 the presentation was of sufficient severity to suggest torsion. Two of these 4 were managed conservatively, and spontaneous recovery resulted. Surgical exploration of the scrotum in the other 2 revealed evidence of vasculitis in both and the possibility of torsion of appendix epididymis in 1. In patients with Henoch-Schölein purpura and scrotal pain and swelling, a conservative approach with cautious observation appears justified.


Corpus cavernography prior to insertion of penile prostheses. Our experience with corpus cavernography prior to the insertion of a penile prosthesis is presented. We suggest that this investigative procedure should be used as a routine to determine the patency of the "corporal tubes," particularly in patients in whom corporal fibrosis is a possibility, such as a previous episode of priapism.


Renal cell carcinoma and vaginal metastasis. A case of left renal cell carcinoma which presented as vaginal bleeding from a vaginal metastasis is reported. Less than 60 cases of this occurrence have been described.


Testicular torsion in adults: plea for its consideration early in clinical evaluation of acute scrotum. A case of a thirty-eight-year-old man with acute scrotum is presented. Past history of transient episodes of testicular pain, negative findings on urinalysis, and lack of symptomatic relief despite antibiotic therapy plus a high index of suspicion helped establish the correct diagnosis of testicular torsion. A long delay between onset of symptoms and surgical exploration resulted in testicular infarction. A plea is made to consider torsion of the testis even in the adult with scrotal pain when all of the classic clinical criteria of epididymitis are not present.


Renal malacoplakia.

Renal malacoplakia. A case of malacoplakia of the kidney is presented. The incidental finding of asymptomatic pyuria focused attention on the urinary system. Urologic evaluation concluded an avascular renal mass. The diagnosis of malacoplakia was established only after histologic studies of the surgical specimen were completed. Purulent perinephritis complicated the postoperative outcome.


Percutaneous ureteral splinting.

Percutaneous ureteral splinting. Percutaneous ureteral splinting using a modified catheter technique is described, and experience in treating 5 patients (4 with postoperative fistulas and 1 with stricture) is reported. The method offers an effective alternative to surgery in achieving ureteral splinting and renal drainage.


Urographic imaging in neonatal period: radionuclide scan and x-ray. A retrospective study of efficacy of radioisotopic renal scan intravenous urogram in 10 infants with various urologic diseases showed the scan to be more rapid and accurate in depicting the lesions. Since the radioisotopic renal scan requires less irradiation than the intravenous pyelogram, it should be used first as a screening test in infants suspected of having urologic problems.


Male infertility practice and Orthodox Jewish law. The evaluation and management of infertility problems in Orthodox Jewish couples can be made difficult because of restrictions which may be imposed by religious rules. The origins of the religious laws governing semen collection, diagnostic and therapeutic genital surgery, menstruation, and homologous and donor insemination are reviewed. Contemporary rabbinic authorities are quoted; their opinions may serve as guidelines for the patient and urologist dealing with infertility problems.


Systemic effects of hypernephroma.

Systemic effects of hypernephroma. In a study of 30 patients with hypernephromas, 23 patients manifested systemic effects of the tumor, and in 5 of these, the systemic effects were the presenting feature that led to the diagnosis. In contrast to this, only 17 patients had urologic complaints, and no single patient in this study had the classic triad of hematurial, loin pain, and mass. Weight loss (52 per cent), pyrexia, and elevated sedimentation rate (36 per cent) were seen most frequently. Anemia was seen in 25 per cent of patients. Other features seen in this group wer abnormalities in liver function, elevated alkaline phosphatase, hypertension, erythrocytosis, and hypercalcemia. In the majority of instances, removal of tumor was associated with remission of these effects. The effects were classified as those of a general toxic nature, those due to normal or abnormal production of hormones, and those due to production of abnormal substances by tumor cells. The evaluation of these effects was useful in making an early diagnosis and in follow-up care.


Renal cyst puncture and abscess formation. Percutaneous needle puncture and aspiration of suspected cystic renal masses may provide accurate diagnosis in selected cases. However, renal cyst puncture is not a totally innocuous procedure and certain complications may be encountered. Report is made of 2 cases of renal cyst puncture followed by abscess formation, necessitating surgical intervention. An improved technique involving surgical preparation of the operative area and utilization of double-needle method of cyst puncture is advocated.


Glaucoma after pars plana vitrectomy.

Glaucoma after pars plana vitrectomy. Elevation of intraocular pressure is a relatively common complication after pars plana vitrectomy. Seven cases illustrate the diverse causes of the pressure rise that may be seen in these patients. Blood in the anterior chamber, retained lens material, inflammatory debris, topical corticosteroid administration, rubeosis iridis, and pre-existing, chronic open-angle glaucoma have all been implicated, singly or in combination, in the elevation of intraocular pressure that occurs after pars plana vitrectomy. Diabetic patients are particularly susceptible to the simultaneous occurrence of more than one of these factors.


Plateau iris syndrome.

Plateau iris syndrome. Eight cases of the plateau iris syndrome are presented. The "plateau iris syndrome" should be differentiated from the "plateau iris configuration." The "configuration" refers to a preoperative condition in which gonioscopically confirmed angle-closure glaucoma occurs, but the iris plane is flat and the anterior chamber is not shallow axially. In most cases, the angle-closure glaucoma associated with the plateau iris configuration is cured by a peripheral iridectomy. "Plateau iris syndrome" refers to a postoperative condition in which a patent iridectomy has removed the relative pupillary block which is ordinarily important in causing angle closure, but gonioscopically confirmed angle closure recurs without shallowing of the anterior chamber axially. Plateau iris syndrome is rare compared to the configuration, which itself is not common. In the syndrome, angle closure usually occurs in the early postoperative period but may occur long after iridectomy when the pupil dilates spontaneously or in response to mydriatic agents. It usually occurs in a younger age group than ordinary angle-closure glaucoma. The treatment is the use of pilocarpine postoperatively as long as it is needed. This syndrome must be considered in the differential diagnosis when the intraocular pressure rises unexpectedly following an adequate peripheral iridectomy procedure for angle-closure glaucoma.


Problems in the differential diagnosis of choroidal nevi and malignant melanoma. XXXIII Edward Jackson Memorial lecture. Failure to appreciate the variability in the natural course of choroidal nevi (benign melanomas) has caused the adoption of a misleading cytologic classification of malignant melanomas. This classification is not based on adequate clinical observation, reliable cytologic criteria for malignancy, or sufficient autopsy information. The available evidence suggests that spindle A tumors are benign and that spindel B tumors, although capable of local destruction of the eye, metastasize infrequently. The risk of observation of small melanocytic tumors must be weighed against the risk that early enucleation or other forms of therapy may not favorably affect prognosis. The clinical observations to date at the Bascom Palmer Eye Institute indicate that the risks of observation are low.


Visual field changes following acute elevation of intraocular pressure. Visual field, acuity, and optic nerve head were evaluated in 24 patients with transient but marked elevations in intraocular pressure. The patient population consisted of 16 patients with angle-closure glaucoma and 7 with high tensions following cataract surgery. In all cases, duration and extent of pressure elevation is documented as well as subsequent visual field, acuity, and fundus examinations. In selected cases, visual field determinations were made during the acute pressure elevation. Previous reports of patients with acute pressure elevation are reviewed. The general absence of glaucomatous field defects in this patient population is discussed with respect to the possible pathogenesis of field loss seen in chronic simple glaucoma.


The use of the 32P test in the management of malignant melanoma of the choroid: a five-year follow-up study. We have presented mortality, clinical, and histopathologic data on a consecutive group of patients with malignant choroidal melanoma studied by a radioactive phosphorus uptake test. The mortality of 14% is the lowest reported in the literature (Table 11) and suggests that early diagnosis followed by prompt enucleation affords the patient a favorable prognosis. There is no evidence to suggest that the surgical manipulations involved expose the patient to added risks. Factors of importance regarding prognosis of malignant melanoma include tumor size, cell type, and presence or absence of extrascleral extension. Of these, we believe that cell type is the most important factor. Our data to date do not permit us to predict from the 32P tests the prognosis for patient survival.


Operative complications of goniotomy.

Operative complications of goniotomy. During 320 anesthesias, 401 goniotomies were performed and are here reviewed. Significant complications were cardiopulmonary arrest (1.8%) and postoperative hemorrhage (0.5%). Useful vision was lost in one case (0.2%). No complications could be attributed to operating on both eyes during the same anesthesia. The authors believe that both eyes should be operated on during the same anesthesia when bilateral goniotomy is indicated.


Histopathologic observations on human eyes following cyclocryotherapy for glaucoma. This is a clinicopathologic study of 12 human eyes that previously had been subjected to cyclocryotherapy. In ten cases detailed information was available regarding technical factors, such as temperature of the cryoprobe at the time of surgery and the like. The interval from treatment to enucleation ranged from 12 days to 4 1/2 years. On pathologic examination permanent, often massive, destruction and scarring of both layers of the ciliary body's epithelium was found in all 12 patients. The pigment epithelium was more susceptible to cryosurgical damage than was the nonpigment epithelium. Scarring of the ciliary body stroma and muscle occurred in 11 patients, scleral damage was present in 9, and a fibrous membrane lined the inner surface of the ciliary body in  5. This study indicates that cyclocryotherapy is an effective way of inducing permanent destruction of the human ciliary epithelium. Factors other than regrowth of epithelial cells account for failure to control the intraocular pressure in those patients in whom cyclocryotherapy proves ineffective.


6-Hydroxydopamine therapy in glaucoma.

6-Hydroxydopamine therapy in glaucoma. At the inception of this study, 6-hydroxydopamine (6-HD) was administered to 137 eyes of 100 glaucoma patients by subconjunctival injection (27 applications) and later by iontophoresis (202 applications). Eighty-four patients were receiving maximum medical therapy, and 24 had had previous glaucoma surgery. Seventy-seven had primary open-angle glaucoma. In 49 patients with data adequate for analysis, 6-HD therapy was effective in 41%, questionable in 31%, and not effective in 28%. The median peak-pressure drop was 13 mm Hg from a baseline of 26 by subconjunctival injection and 6 mm Hg from a baseline of 24 by iontophoresis. The median effective period before return to baseline pressure was 2.5 months. There was a direct correlation between the effectiveness of epinephrine therapy with and without 6-HD. Iontophoresis is a much more practical method for the administration of 6-HD.


Correction of facial contour deformities resulting from loss of soft tissue or bone. Two methods of recovering normal contour of the orbit are presented in which ocularists and ophthalmologists equally participate. One method is for correction of the deep supratarsal retraction following soft tissue atrophy; the other technique is indicated when there has been loss of or major displacement of bone of the orbital rim. Frequently, these two techniques must be used concomitantly in complex reconstructive cases.


Primary optic nerve meningiomas: clinical presentation and management. Fifteen patients with meningiomas arising from the optic nerve sheath within the orbit occurred in a large series of patients with orbital tumors. Eleven patients were women; there was only one child. Thirteen patients had a similar clinical appearance. In each case visual loss was the first symptom. Proptosis, which occurred in only ten patients, developed later (the time interval was three months to five years). Optic disc edema or atrophy was present in all 15 patients, some of whom had optociliary shunt vessels on the optic disc. The new fine-matrix EMI scanner (320x320) demonstrated the tumors but even clearer pictures of the lesion could be obtained using a c-mode ultrasonic scanner. The treatment of these meningiomas is essentially surgical.


New diagnostic techniques for the evaluation of orbital trauma. Midfacial trauma can produce fractures and soft tissue injuries and can embed foreign bodies within the eye, orbit, and brain. A careful history and ocular examination are fundamental to the evaluation of any patient who has suffered orbital injuries. Damage to the paranasal sinuses and the nasolacrimal system should be considered as a possible consequence of trauma to the orbit. Fractures are best evaluated by conventional roentgenograms with linear or hypocycloidal tomography. Bony fragments can be well visualized by xeroradiography. Positive contrast orbitography may be hazardous and has been replaced by noninvasive diagnostic techniques. Computerized tomography is useful in localizing soft tissue injuries and foreign bodies. Damage within the eye may be evaluated by ultrasonography. Cerebrospinal fluid leaks can be diagnosed by radionuclide cisternography, using nasal sample counting or scintiphotographic imaging. Carotid-cavernous sinus fistulas and other vascular abnormalities may be investigated by radionuclide angiography at minimal risk to the patient.


The use of scleral transplantation in cicatricial entropion and eyelid retraction. Scleral transplantation has given excellent results in the surgical repair of eyelid problems. The advantages of using scleral transplantation in repairing eyelid retraction are the relative predictability of the final eyelid position and curve and the decreased incidence of repeated retraction. The characteristics of sclera make it a desirable homologous transplant material for use in transplant surgery.


The use of cryotherapy for trichiasis.

The use of cryotherapy for trichiasis. Cryosurgical destruction of aberrant eyelashes was performed on 72 eyelids. Seven of nine failures occurred following major deviation from recommended technique. All but one recurrence were successfully re-treated. Notching of the eyelid was observed in one patient. The technique utilized a nitrous oxide gas-cooled cryoprobe. Tissue temperature was monitored by a subcutaneous microthermocouple in the region of the lash follicle to -20 C in a double freeze-thaw cycle.


The role of cryosurgery in external ocular and periocular disease. This preliminary report suggests that cryosurgery has a definite place in the management of certain external periocular and ocular problems. Cryosurgery for basal or squamous cell carcinoma of the lid is easily performed, gives excellent cosmetic results, and has a low recurrence rate. It is not recommended for lesions involving the fornices, or sclerotic and morphea-type basal cell carcinomas. Tumor recurrences following radiation, surgery, or cryosurgery can still be retreated with cryosurgery. To date, there is no evidence that cryosurgery at temperatures above -40 C causes damage to the lacrimal outflow system. Cryosurgery is of value in the management of trichiasis, reactive lymphoid hyperplasia, spider hemangioma, molluscum contagiosum, and conjunctival dysplasia. Cryotherapy for management of intraepithelial epithelioma and squamous cell carcinoma of the conjunctiva and cornea is still under investigation. Cryosurgery will, in our opinion, become the treatment of choice for basal and squamous cell carcinomas of the eyelids. The 96% cure rate with one treatment for these lesions reported here is artificially high since the follow-up  period is too short. However, retreatment with cryosurgery is a simple ten-minute outpatient procedure which is certainly not the case with recurrences after other forms of therapy.


IgE in respiratory tract allergies.

IgE in respiratory tract allergies. The IgE concentration was determined in the sera and nasal secretions of 166 patients with nasal allergy, 40 patients with bronchial asthma, and 50 control subjects, using Phadebas IgE kits. The IgE level was significantly elevated in both the sera and nasal secretions of allergic patients. The sera and nasal secretions of 142 patients, who were positive in HD or mites skin test, were subjected to a radioallergosorbent test (RAST) for estimating the specific IgE antibody activity to mites. The gradings of the specific antibody activity were significantly correlated with the strengths of the HD skin tests. The results of this study proved the usefulness of the determination of IgE and specific IgE antibodies in the diagnosis and study of the pathogenesis of respiratory tract allergies. The IgE in nasal secretions was much more closely related to pathogenesis of respiratory allergies than was IgE in sera. However, unless more concentrated nasal secretions are assayed, the diagnostic value is limited.


Comparison of electrically and acoustically evoked responses in the auditory cortex of the guinea pig: implications for a cochlear prosthesis. Guinea pigs have been used to develop an animal model for evaluation of electric stimulation of the cochlea. Techniques were developed for recording from single neural units in the auditory cortex. Acoustic responses exhibit similar patterns of neural discharge ("on", "off", sustained excitation and inhibition, etc) to those reported for auditory neurons in other species. Similar response patterns are obtained when electric stimulation is used. However, cortical units display characteristic frequency tuning with acoustic stimulation, whereas it becomes increasingly difficult to evoke electric responses as stimulus frequency increases. Recording of gross evoked responses from the same cortical area indicates that the intensity function for electric stimulation is much steeper than that seen for acoustic stimulation.


Studies on immunity to mouse sarcomas using the tumor-cell neutralization test. Statistical analysis of the results of tumor-cell neutralization (Winn) tests has been presented in a refined manner using three variables: tumor incidence, time to palpable tumor, and growth rate. The concept of relative risk and the Z statistic were used to describe the latter two variables. This analysis is then applied to a particular experiment. Lymphocytes sensitized in vitro were compared with specifically immune lymphocytes and were found to facilitate the growth rate. Further applications of this analysis are discussed.


Rehabilitation of partial laryngectomy patients. Rehabilitation and function following three anatomically discrete forms of partial laryngectomy (hemilaryngectomy, subtotal supraglottic laryngectomy, and partial laryngopharyngectomy) were studied in 68 patients. Study parameters included posttreatment respiration, deglutition, taste, smell, and hearing function; articulation and voice analysis; and social, communicative, and vocational adjustment. The major portion of the study involved specific testing of posttreatment voice quality and articulation. Recorded word lists and sentences were evaluated by independent observers regarding breathiness, hoarseness, harshness, pitch, loudness, and intelligibility. These data were analyzed employing a Statistical Package for the Social Sciences (SPSS) through the Washington University computer facilities.


The observation, using an infrared video system, of patients' eye movements resulting from vestibular stimulations and their comparison with electronystagmographic data. An infrared video technique is presented for the observation and documentation of patients' eye movements during vestibular stimulations in total darkness. Results from the comparison of the video and electronystagmographic information indicate that the infrared video technique is a useful diagnostic aid for vestibular evaluation and in some instances may be necessary. Further, the data from two-channel electronystagmographic recordings may be misleading even when the patient is tested in total darkness with eyes open.


Hearing loss of a central type secondary to carbon monoxide poisoning. The effect of carbon monoxide poisoning on the threshold sensitivity of the responses from the auditory cortex, inferior colliculus, and cochlea to acoustic stimuli in guinea pigs was studied. The toxicity of carbon monoxide is believed to be secondary to tissue hypoxia and is partially reversible. Loss of auditory threshold sensitivity in carbon monoxide poisoning is most prominent at the auditory cortex. The loss of sensitivity at the inferior colliculus is the next most severe. There is no loss of sensitivity at the cochlea. The relative vulnerability of the central auditory pathway to carbon monoxide poisoning as compared with the end organ is demonstrated.


Asymptotic threshold shift in people with sensorineural hearing loss. Twelve men with mild to moderate sensorineural hearing loss in the frequency range of 3 to 6 kHz were exposed to 24 hours of continuous noise. The noise was an octave band centered at 4 kHz at a level of 85 dB. Hearing thresholds were measured monaurally at 11 test frequencies ranging from 250 to 10,000 Hz prior to exposure and at selected intervals during and after exposure. Temporary threshold shift (TTS) development followed a similar time course to that observed in normal hearing subjects, asymptotic levels being reached between 8 and 12 hours of noise exposure. Maximum TTS occurred at 4 and 6 kHz. The amount of TTS was less for the subjects with sensorineural hearing loss than for people with normal hearing. However, the sound pressure level required to detect pure tone (shifted thresholds) following noise exposure was greater in the group with hearing loss than was measured in the normal hearing subjects. Within the limits of this experiment, a sensorineural hearing loss does seem to exert a significant effect on change in hearing sensitivity resulting from noise exposure.


Predicting hearing loss from stapedial reflex thresholds in patients with sensorineural impairment. We have demonstrated the elevated reflex thresholds and decreased bandwidth effect in listeners with sensorineural hearing loss, and we have extended this generalization to include those with hearing loss related to presbycusis. A bivariate plotting method has been described for predicting hearing loss from reflex threshold data that is characterized by a low rate of false positives, while successfully identifying those with a moderate degree of hearing loss (greater than 32 dB) more than 80% of the time. We found no evidence of decreasing reflex threshold with age. Instead, our reflex thresholds for normal hearing subjects tend to remain the same or increase slightly as age increases. It is hoped that these findings will stimulate further work to correlate reflex thresholds with hearing levels. This information should be used to test infants (especially those at high risk for hearing loss) and other subjects unable to respond to conventional audiometric testing.


The onset of a refractory response to androgens in the anemia of bone marrow failure. Patients with bone marrow failure may have a hematopoietic response to an androgen preparation after they have no response from the use of a previous testosterone preparation. The failure to try a variety of hormone preparations may lead to improper conclusions as to a potential marrow proliferation for a clinical response. In some instances the use of a 5beta steroid metabolite may initiate stem cell proliferation in patients previously refractory to testosterone or nontestosterone esters. These obsevations suggest that some patients refractory to testosterone may be unable to form adequate 5beta metabolities by alterations in 5alpha reductase or enhanced metabolic transformation of the androgen. All patients should be evaluated with several androgen esters before concluding that their marrow cannot achieve a hematopoietic response.


Cartilage regeneration: a clinical and experimental study. Regeneration of the alar cartilage has been observed in patients undergoing revision rhinoplasty. Material preserved from the first procedure was compared to that removed at the secondary procedure. Microscopic findings confirm the cartilage regrowth. An experimental study was undertaken to determine if cartilage regeneration could be reproduced in animals. White New Zealand rabbits were utilized in the study. Gross and microscopic findings indicate that cartilage does regenerate if the perichondrium is not removed.


Studies on the pathogenesis of cancer hypercalcemia. The pathogenesis of hypercalcemia in cancer continues to challenge the clinical investigator. Some aspects of this subject have been reviewed, notably with respect to the possible roles of prostaglandins and osteoclast activating factor, with particular reference to breast cancer. There is considerable evidence that the former humoral factor is operative and beginning evidence that the latter may be also. The hope in this continued work is that with better understanding of the mechanisms of hypercalcemia and bone loclization of tumors we will be in a far better position to control and interdict this localization.