Teratology and percutaneous toxicity studies on hair dyes.

Twelve hair dye formulations were tested for systemic toxicity by topical application twice weekly for 13 wk to groups of 12 New Zealand white rabbits and for teratologic effects following applications to groups of 20 pregnant Charles River CD rats on days 1, 4, 7, 10, 13, 16, and 19 of gestation. The three semipermanent formulations were applied as is, and the nine oxidation dyes were mixed 1:1 with 6% hydrogen peroxide just prior to application, as in normal use. The formulations induced a broad spectrum of dyes and dye intermediates used or considered useful in oxidative and semipermanent hair color products. In the teratology study no biologically significant soft tissue or skeletal changes were noted. Similarly, the mean numbers of corpora lutea, implantation sites, live fetuses, and resorptions per pregnancy, as well as numbers of litters with resporptions, were not significantly affected by the dye treatment. In the percutaneous toxicity study there was no evidence of compound-induced systemic effects. Microscopic examination of 25 tissues from each animal gave no indication of histomorphologic evidence of toxicity. No dye discoloration of urine was seen at any time during the test or at necropsy. Some of the dye groups showed epidermal hyperplasia, which was probably a reflection of slight irritation due to the frequency of application of the oxidation formulations.


Strain differences in histopathologic, hematologic, and blood chemistry changes induced in mice by a technical and a purified preparation of 2,4,5-trichlorphenoxyacetic acid.

Including controls, 978 mice were studied. On days corresponding to days 6 through 14 of pregnancy, groups of pregnant and nonpregnant CD-1 mice and male and nonpregnant female dihybrid cross F2 mice received by gavage 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) ranging in dosage from 30 to 140 mg/kg. Some groups received a technical preparation containing 97.9 +/- 0.4% 2,4,5-T and some a purified preparation containing 99 +/- 0.3% 2,4,5-T. Mice were sacrificed when they became moribund and at 1, 2, 4, 6, 8, and 11 days after beginning treatment. Sick or moribund mice sacrificed after 2-9 doses of 2,4,5-T often showed severe myocardial lesions, hypocellularlity of the bone marrow, and depletion of lymphocytes in the thymus, spleen or lymph nodes. They also showed marked hematologic and blood chemistry changes. Treated mice remaining healthy showed few or no lesions or blood chemistry changes, but often developed a mild anemia attributable to a hemolytic effect of 2,4,5-T. The incidence of animals becoming moribund was less than 1% in the CD-1 mice, including those given 140 mg/kg, and 53-82% in groups of male and female F2 mice receiving 120 mg/kg 2,4,5-T. The incidence of moribund mice tended to be higher in male than in female F2 mice and in those given the purified compound. These findings indicate that impairment of maternal health by severe lesions early in gestation is not the primary cause of an increase in incidence of fetal abnormalities observed in mice given 2,4,5-t. they also indicate that the lesions are due primarily to 2,4,5-T, rather than contaminants in the technical preparation, and illustrate the importance of using more than one strain of mouse in a toxicologic or teratologic study.


Metabolism of 109Cd in rats fed normal and low-calcium diets.

Growing male rats were fed purified diets that contained either 0.6% or 0.1% calcium to investigate the relationship of calcium intake to the uptake, tissue distribution, and excretion of 109Cd. An equal number of rats were fed either the 0.6 or 0.1% calcium diets for 4 wk before they were used for experiments. In the first experiment 11 rats from each dietary group were administered 5 muCi 109Cd by stomach tube and were then maintained in metabolism cages for 72 hr. Animals fed the low-calcium diet took up more 109Cd, as significantly higher levels of radioactivity were found in the intestinal mucosa, serum, lungs, liver, kidneys, and urine and a significantly lower level was found in the feces. Higher levels of 109Cd, associated with low-molecular-weight proteins that may be related to the absorption process, were found in the intestinal mucosa of the low-calcium group. In the second experiment 10 rats from each dietary group were administered 5 muCi 109Cd by subcutaneous injection and then maintained in a metabolism cage for 72 hr. No significant differences were found in the distribution or excretion of 109Cd except for the lungs where radioactivity was greater in the low-calcium group. The results of the study indicate that the enhanced cadmium toxicity observed in calcium-deficient animals exposed to the heavy metal is the result of an increased uptake from the small intestine.


Effects of platinum and palladium salts on parameters of drug metabolism in rat liver.

The effects of various salts of platinum of palladium were determined on the parameters of the microsomal mixed-function oxidase system from rat liver. The intraperitoneal injection of PtCl4 or Pd(NO3)2 increased the hexobarbital-induced sleeping time in vivo and generally decreased the aminopyrine demethylase and the content of cytochrome P-450 in isolated hepatic microsomes. The dietary administration of various salts of platinum or palladium for 1 wk generally decreased or had no effect on the parameters of drug metabolism by isolated microsomes and after 4 or more wk generally had no effect on, or increased, the parameters. The addition of 0.15-0.2 mM PtCl4 or 0.2-0.3 mM Pd(NO3)2 to the incubation medium (containing 5 mM MgCl2) inhibited the aminopyrine demethylase of isolated hepatic microsomes by 50%.


Lupin alkaloids from teratogenic and nonteratogenic lupins. III. Identification of anagyrine as the probable teratogen by feeding trials.

Alkaloidal extracts from teratogenic lupins produced congenital deformities in calves typical of crooked calf disease when the extracts were administered to pregnant cows during the susceptible gestational period. These data and previous epidemiologic studies suggest that one of the four alkaloids in the preparation, anagyrine, is the responsible teratogen. Severity of the malformations was directly related to the level of anagyrine present in the preparations administered.


Lupin alkaloids from teratogenic and nonteratogenic lupins. IV. Concentration of total alkaloids, individual major alkaloids, and the teratogen anagyrine as a function of plant part and stage of growth and their relationship to crooked calf disease.

The concentrations of total alkaloids and individual major alkaloids including the teratogen anagyrine were measured in various plant parts of teratogenic lupins as the plants matured. All alkaloids including angyrine were high in concentration in above-ground parts early in growth and decreased as plants matured, except for an increase in mature, intact seeds. Seeds were highest, followed by early growth leaves and stems. Roots were lowest with mature leaves and stems only slightly higher. Pregnant cows have the greatest risk of giving birth to calves with crooked calf disease when the concentration of the teratogen anagyrine is highest and the cows are in the susceptible 40-75 day gestation period when ingesting the plant.


Reproductive, teratologic, and mutagenic studies with some polydimethylsiloxanes.

The purpose of these studies was to evaluate the effects of selected polydimethylsiloxanes on reproduction and fetal development in rats and rabbits and to determine the mutagenic potential of one such material in mice. In two separate three-phase studies in rats and rabbits with a 350 centistoke medical grade fluid, the only significant effect noted was an apparent dose-related incidence of in utero mortality at dose levels of 200 and 1,000 mg/kg sc in rats in one study. No evidence of fetotoxicity was obtained in the second study at the same dose levels. The incidence of talipes varus at a sc dose level of 200 mg/kg in rabbits (8.8%) is at or above that expected for control populations. The nonoccurrence of talipes varus at the higher level of 1,000 mg/kg and the absence of this defect in the companion study casts doubt on the significance of this finding. A 7-cs pump fluid was nonteratogenic in rats at oral doses as high as 1,000 mg/kg and was nonmutagenic in ma1e mice at ip doses of 5 and 10 g/kg. A 10-cs fluid was nonteratogenic in rabbits at a dermal dose level of 200 mg/kg.


Sublethal effects of chronic lead ingestion in mallard ducks.

Mallard drakes (Anas platyrhynchos) fed 1, 5, or 25 ppm lead nitrate were bled and sacrificed at 3-wk intervals. No mortality occurred, and the pathologic lesions usually associated with lead poisoning were not found. Changes in hematocrit and hemoglobin concentration did not occur. After 3-wk ducks fed 25 ppm lead exhibited a 40% inhibition of blood delta-aminolevulinic acid dehydratase activity that persisted through 12 wk exposure. After 12 wk treatment similar enzyme inhibition was present in the ducks fed 5 ppm lead. At 3 wk there was a small accumulation of lead (less than 1 ppm) in the liver and kidneys of ducks fed 25ppm lead; no further increases occurred throughout the exposure. No significant accumulation of lead occurred the the tibiae or wing bones. Groups of ducks fed 5 and 25 ppm diets for 12 wk were placed on clean feed and examined through a 12 wk posttreatment period. After 3 wk on clean diet delta-aminolevulinic acid dehydratase activity and lead concentrations in the blood had returned to pretreatment levels. Even though lead concentrations in the blood, soft organs and bone were low, a highly significant negative correlation between blood lead and blood enzyme activity was obtained. This enzyme bioassay should provide a sensitive and precise estimate for monitoring lead in the blood for waterflow.


Phytochemical and toxicological screening of household ornamental plants potentially toxic to humans. I.

Thirty different genera of household ornamental plants have been investigated to determine the loci and natures of potential toxins and any injurious effects produced in experimental animals. Different plant parts were tested for alkaloids, glycosides, steroids, saponins, and cyanogenic glycosides. At least seven genera showed detectable concentrations of alkaloids. Glycoside tests were variable, and there was an indication that several species may contain steroid components. Sixteen genera showed positive saponin foam tests. None of the species were clearly cyanogenic. Preliminary biologic screening on rats and mice is given.


Heptachlor: toxicity to and uptake by several estuarine organisms.

Technical-grade heptachlor (65% heptachlor, 22% trans-chlordane, 2% cis-chlordane, and 2% nonachlor) was tested in 96-hr bioassays to determine its toxicity to estuarine animals. The test organisms and the 96-hr LC50 or EC50s based on measured concentrations in water) are as follows: American oyster (Crassostrea virginica), 1.5 mug/liter; pink shrimp (Penaeus duorarum), 0.11 mug/liter; grass shrimp (Palaemonetes vulgaris), 1.06 mug/liter; sheepshead minnow (Cyprinodon variegatus), 3.68 mug/liter; pinfish (Lagodon rhomboides), 3.77 mug/liter; and spot (Leiostomus xanthurus), 0.85 mug/liter. Analytical-grade heptachlor (99.8% heptachlor) and heptachlor epoxide (99%) were also studied. The analytical-grade heptachlor 96-hr LC50 for pink shrimp and spot was 0.03 mug/liter and 0.86 mug/liter, respectively, while that for pink shrimp exposed to heptachlor epoxide was 0.04 mug/liter. Heptachlor was accumulated and some metabolized to its epoxide by all animals tested. Fish and oysters accumulated heptachlor in their tissues 2,800-21,300 times the measured concentration in water; shrimp, only 200-700 times.


Elution of benzo[alpha]pyrene from carbon particles in the respiratory tract of mice.

The effect of carrier particle size on the rate of dissociation of benzo[alpha]pyrene (BaP) from carrier particles deposited in the respiratory tract of mice was studied. BaP-coated carbon particles (in two size ranges, 0.5-1.0 and 15-30 mum) plus 103Ru-tagged carbon tracer particles were intratracheally instilled in mice. The clearance of carbon particles and the simultaneous rate of elimination of BaP from the respiratory tract was measured. BaP adsorbed to 15- to 30-muM carbon particles was eliminated from the lung at essentially the same rate as the carbon particles were cleared. In contrast, BaP adsorbed to 0.5- to 1.0-muM carbon particles was eliminated from the lung approximately 4 times faster than the carbon particles were cleared. The persistence of carcinogens and their rates of elution from carrier particles are discussed in relation to the pathogenesis of lung cancer in animals treated with carcinogen-carrier particle preparations.


DNA damage produced by povidone-iodine in cultured human diploid cells.

Povidone-iodine is capable of selective altering the DNA of human diploid cells growing in culture. This finding extends to eukaryotic cells, the previously reported DNA-modifying activity of this agent for bacteria. In view of the known relationship between DNA-modifying activity and potential carcinogenicity, the results suggest that the potential hazards posed by the widespread use of this agent be evaluated.


Effect of mycotoxins on uptake and degradation of [125I] albumin in mouse liver and kidney lysosomes.

Some mycotoxins have been evaluated with respect to effects on the reticuloendothelial function of uptake and degradation of a soluble, denatured protein in phagolysosomes isolated from mouse liver and kidneys. Toxins were dissolved in dimethylsulfoxide and administered intraperitoneally. Particulate fractions isolated from liver and kidney homogenates were assayed for proteolytic activity within osmotically active particles (phagolysosomes). Treatment with citrinin, penitrem A, streigmatocystin, and zearalenone produced inhibition of proteolysis in kidney but not in liver phagolysosomes. Moniliformin and T-2 toxin had no detectable effect on lysosome formation or function in either tissue. The phagolysosomal toxicity of these compounds appeared to be more toward kidney than liver. Both sterigmatocystin and zearalenone caused an increase in kidney phagolysosomal fragility at early times after treatment, and all agents except penitrem A caused a decrease in uptake of labeled albumin into kidney cells. Citrinin labelized kidney phagolysosomes in vitro but not in vivo, while only citrinin and zearalenone inhibited in vitro preparations of cathepsin.


Influence of certain metals on the level of metallothionein-like proteins in the liver and kidneys of rats.

Rats were given certain metal salts once every other day for six to eight doses and therafter the levels of metallothionein-like proteins (MTP) were determined in their liver and kidneys. The normal level of those proteins ranged from 0.1 to 0.4 mg/g in the liver and 0.2 and 0.6 mg/g in the kidney. Beryllium, magnesium, barium, strontium, tin, arsenic, selenium, chromium, and nickel administration did not influence the tissue levels of MTP. There was a tendency toward increased MTP levels in the liver after the application of high doses of iron. A significant increase in MTP levels in the liver resulted from cobalt administration and in the kidneys of bismuth-treated rats. Applying molecular filtration it was shown that both metals were partially bound in vivo to protein fractions, the molecular weights of which are close to that of metallothionein.


A quantitative rotational test of vestibular function.

This paper describes a quantitative vestibular test in which the stimulus is a constant angular acceleration of 3 degrees/sec2 for 80 sec. The nystagmus output is plotted as cumulative slow phase eye displacement against time and is displayed on an oscilloscope screen along with the output from a mathematical model describing vestibulo-oculomotor function. External dials allow one to change the equation constants thereby altering the shape of the model output. Values for equation constants which match the model output to the patient can be read directly from the dials, thus providing a description of the vestibular system under test. Results indicate that vestibular asymmetry (manifest by spontaneous nystagmus is not uncommon in normals, and only when spontaneous nystagmus is coupled with vestibular gain does one get a measure of abnormality. The significance of altered vestibular parameters in certain pathological states is discussed.


[Long-term antibiotic therapy in chronic purulent otitis media].

A new therapeutic approach is proposed for chronic purulent otitis media. This clinical condition is often a recurring phenomenon in spite of all forms of treatment. Ten cases are reviewed and the results encourage the authors to pursue this form of treatment consisting of a longterm antibiotherapy of Ampicilline and Cloxacilline in a further study.


Hydrocephalus following translabyrinthine surgery.

Hydrocephalus has been identified and surgically treated with ventricular peritoneal shunts in two of 150 patients following translabyrinthine microsurgical removal of acoustic tumors. This problem has prompted a review of the subject of hydrocephalus in general and "otitic hydrocephalus" in particular in relation to contemporary extended temporal bone surgery.


Epidural hemorrhage, a rare complication of otitis media.

Extradural hemorrhage caused by otitis media is so rare that only four cases were found in a search of the literature. Certain striking similarities and the singular absence of a major demonstrable bleeding vessel in all cases appear more than coincidental and we have proposed a theory to explain the cause of the hemorrhage.


Bilateral temporal bone metastases of a uterine cervix carcinoma.

A case is reviewed of bilateral temporal bone metastases from a carcinoma of the uterine cervix. The pertinent literature is reviewed and the temporal bone histology is described.


Vocal restoration following laryngectomy.

Methods of vocal restoration after laryngectomy are summarized and a new approach briefly described. It is emphasized that surgical procedures should only be contemplated when a satisfactory esophageal voice has not been achieved.


Systemic lupus erythematosus with a vocal cord granulomatous nodule.

Systemic lupus erythematosus (SLE) with subcutaneous granulomatous nodules, joint symptoms, and a positive latex titre for rheumatoid factor may cause diagnostic confusion with rheumatoid arthritis (RA). This has been a subject of renewed interest in recent medical literature, but reports of nodules in SLE outside the subcutis are rare. This report presents a patient with SLE and with a vocal cord granulomatous nodule, arthralgia, and a positive latex titre for rheumatoid factor. The laryngeal manifestations of SLE are discussed.


[Non-instrumental traumatic rupture of the hypopharynx and the cervical esophagus].

We present four cases of non-instrumental traumatic ruptures of the hypopharynx and the esophagus. Three are ruptures with closed neck and one with a rupture associated with a cervical wound. A conjoined lesion of the airway is usual, except in one of our observation. All people injured come from car, sport, or work accidents. The esophageal wound, contaminating the mediastinum, is life-threatening and requires a rapid therapeutic solution: wide drainage tube and antibiotics. The diagnosis, often difficult due to poor symptomatology, must be thought of when there is any severe trauma of the cervical region.


Mucocele of the sphenoid sinus presenting as spontaneous pneumocephalus.

A 60 year old woman presented with headaches and a destructive lesion in the sella turcica. She refused treatment but returned seven years later with a spontaneous pneumocephalus and dementia. A mucocele of the sphenoid sinus was discovered. Her symptoms resolved after removal of the mucocele and obliteration of the sphenoid sinus.


[Physiopathology of spontaneous extravasation of urine in the upper urinary tract. Apropos of 24 cases].

Extravasation of urine was seen in 24 intravenous pyelograms taken for renal colic during the year 1973-74. A number of the patients presented with an acute abdomen. Extravasation took place of retained urine under pressure in the renal pelvis with leakage either around the clayces, from a fissure in the pelvis or even around the ureter. Extravasations of this type are in general rabsorbed without trace. In 5 cases, operation was necessary to drain a purulent collection which had developed in association with the extravasated urine.


[Post-operative course in tetraplegics after urological surgers (author's transl)].

The authors report their experience with 33 tetraplegics undergoing surgery. The operations were varied, endoscopic (resection of the bladder neck, of the prostate or striate sphincter, lithot-itiasis) or surgical (lombotomies, transintentinal cutaneous ureterostomies). The post-operative course may be dramatic or even fatal (acute hypertension with cerebral haemorrhage). Respiratory insufficiency poses no particular problem and can be controlled. Epidural anaesthesia maintained for several days makes it possible to avoid the more serious problems: -- autonomic hyperreflectivity, -- delayed resolution of ileus and digestive complication. The authors hence use epidural anaesthesia routinely and are satisfied with the technique.


[Standardisation of the terminology of function of the lower urinary tract. Incontinence, cystometry, ureteral profile, units of measurement (author's transl)].

This report contains an initial series of recommendations concerning the terminology of function of the lower urinary tract. It is related specifically to the storage of urine in the bladder, urinary continence and units of measurement. These recommendation were discussed during the 4th Annual Meeting of the International Continence Society at Maintz, Germany in September 1974. This standardisation is proposed in order to facilitate the comparison of results obtained by investigators who use urodynamic methods. It is recommended that the taking into consideration of these standards by noted in written publications, in the "Material and Methods" paragraph or its equivalent: "The methods, definitions and units conforme with the standards proposed by the International Continence Society".


[Hypertension due to limited coarctation of the right renal artery occurring 2 years after left nephrectomy for a "small kidney". 5 year cure obtained by enlargement angioplasty (author's transl)].

The case of a young boy developing hypertension 3 years after removal of a small kidney due to pyelonephritis and vesico-ureteral reflux. Discovery in the artery of the remaining kidney of a limited coarctation without any of the lesions usually responsible for hypertension. Cured by enlargement angioplasty with a 5 year follow-up. This case is interpreted as an example (to our knowledge the only case in the literature) of hypertension, the mechanism of which is that revealed by Schlegel's experiments.


[Association of a benign renal tumor with renal tuberculosis (author's transl)].

The authors present what seems to be the first case in the world of the association of urinary tuberculosis with a benign tumor of the kidney.


Relationship between intrarenal distribution of blood flow and renin secretion during ureteral occlusion.

The present study was undertaken to evaluate the relationship between renin secretion from the denervated kidney and intrarenal distribution of blood flow during reductions in renal perfusion pressure by partial constriction of the aorta with and without ureteral occlusion in the anesthetized dog. In addition, renin contents in different zones of the kidney were measured. A reduction in renal arterial pressure from normal pressure (125-135 mmHg) to 77 mm Hg resulted in significant increase in renin secretion and redistribution of cortical blood flow. A further reduction of renal arterial pressure to 51 mmHg produced a marked increase in renin secretion rate (RSR) without further changes in the intrarenal distribution pattern of blood flow. The pressure reductions during ureteral occlusion increased RSR without any change in the distribution pattern of blood flow, and a decrease in the amounts of extractable renin was found in the outer cortex of the experimental kidney. These findings suggest that renin release occurs mainly in the outer cortex, and this process may be stimulated when the mechanism of autoregulation fails as the perfusion presure approaches to the lower range of autoregulation in the outer cortex.


Epidemiological studies of cerebro-and cardiovascular diseases in the northeast of Japan Part I. Pathological approach to the study in Akita Prefecture.

To define the etiologic factors of Japanese cerebrovascular diseases, a pathological research was conducted on autopsy cases of stroke in Akita Prefecture. In most cases of cerebral hemorrhages, especially in the middle age group (30-59 of age), arteriosclerotic deviations in basal berebral arteries of the circle of Willis and intracerebral small arteries are not found. The authors conclude that cerebral hemorrhage may occur without relationship to disturbances of lipid metabolism, biochemically, and to atherosclerosis, pathologically. Concerning cerebral infarction, especially in the old generation (over 60 years of age), severe arteriosclerotic deviations were recognized both in basal cerebral and intracerebral arteries. These changes were highly influenced by the grade and duration of hypertension, and rarely influenced by hypercholesterolemia. According to the above-mentioned facts, the results obtained from out epidemiological survey were confirmed by the pathological studies.


Quantitative detection of cerebral arteriosclerosis by means of the pressure-velocity hysteresis technique.

The quantitative detection of cerebral arteriosclerosis by means of the pressure-velocity hysteresis technique composed of the cerebral blood velocity pattern (blood velocity pattern in the internal carotid artery measured by the ultrasonic Doppler technique) and the cerebral pressure pulse pattern (common carotid arteriogram measured by non-invasive sphygmography) was investigated in 17-normal young males, normal middle-aged males and patients with cerebral vascular disorders. The ratio of blood pressure/blood velocity in the maximum blood velocity was used as a measure of resistance of the blood flow. The resistance of the cerebral blood flow was significantlpy increased in the patients with cerebral vascular disorders compared to that in the normal young males. The resistance of cerebral blood flow in the middle-aged males was prone to be intermediate between the former two. The results suggest that the pressure-velocity hysteresis technique is useful for the quantitative detection of cerebral vascular resistance as well as cerebral arteriosclerosis. Several factors related to the technique were discussed.


Correlation between myocardial and plasma concentration of digitoxin and its metabolites with special reference to digitoxin radio-immunoassay.

According to our prevous study, the metabolites of digitoxin show nearly dentical affinity with digitoxin antibody. The present study reveals relatively constant ratio of heart to plasma in total 3H-counts, and the concentration of metabolites are ver similar between the two throughout the time investigated which indicates digitoxin concentration of plasma as determined by radioimmunoassay reflects well that of myocardium, although it may contain metabolites.


A histopathological study on the conduction system of the so-called "Pokkuri disease" (sudden unexpected cardiac death of unknown origin in Japan).

The conduction system of seven cases died of the so-called "Pokkuri disease", was histopathologically studied with serial sectioning method. Fibrosis with a significant reduction of conduction fibers was observed in the sinoartrial node and junction between the node and atrial muscle fibers in 6 cases. Abnormal course and branching of the sinus node artery was seen in 6 cases of which 3 had no penetration of its main branch into the node. Some pathological lesions exsisted in the atrioventricular conduction system in 4 cases: 2 had fibrotic lesion in the distal bundle of His and proximal left and right bundle branches which were sandwiched between the abnormal conal muscle and the summit of ventricular septum. Remaining 2 had lipomatous partial interruption in the mid-and distal bundle of His. Simultaneous involvement of sinoartrial node and the atrioventricular conduction system was observed in 4 cases. One of such cases showed abnormal ECG consisted of a left axis deviation and right bundle branch block. As a conclusion, pathological lesions in the conduction system are revealed in more than half of cases of "Pokkuri disease/. The pathgenesis seems to be related to minor anomalies such as abnormal sinus node artery, abnormal conal muscle situation.


The concept of afterload mismatch and its implications in the clinical assessment of cardiac contractility.

The characteristics of left ventricular ejection (velocity and extent of wall shortening) can be analysed in relation to the appropriateness of the matching between afterload and the level of inotropic state (contractility), as modified by the preload (Frank-Starling) reserve. In the normal left ventricle if the preload is not allowed to compensate for an acute increase in afterload, or if the limit of preload reserve is reached, velocity (V CF) and stroke volume will diminish; that is an afterload mismatch occurs. This acute mismatch can be corrected by administration of a positive inotropic agent. In normal conscious animals and in man the ejection phase measures in the basal state  (such as ejection fraction, and VCF corrected for heart size) encompass a relatively narrow range, and when the normal heart adapts successfully to a chronic pressure or volume overload such measures remain normal per unit of muscle. These findings provide the basis for their use in detecting a depressed basal level of inotropic state, even in the presence of certain valvular lesions. When there is mild depression of the basal inotropic state, enhanced preload and dilatation can allow full compensation of VCF, but acute pressure loading can allow detection of the the reduced preload reserve by inducing a substantial fall in stroke volume and VCF. When the basal inotropic state is greatly reduced, a mismatch between afterload and contractility, expressed as reduced VCF or ejection function, will become evident in the basal state even if the afterload is normal. Any increase in aortic pressure will then cause a sharp reduction in stroke volume or VCF. Also, under these circumstances therapeutic afterload reduction with agents such as nitroprusside can increase velocity and extent of wall shortening, and the cardiac output, providing the preload is maintained. The concept of afterload mismatch with limited preload reserve provides a framework for understanding the behavior of the normal or depressed ventrile and how it can operate on a "descending limb" of function. It helps to explain why measures of the ejecting phase (which are sensitive to afterload) appear to be more reliable than isovolumic phase indices (which are relatively insensitive to afterload) for detecting depressed basal inotropic state. Finally, the concept allows for interpretation of the responses observed in the clinical setting to acute and chronic increases and decreases in loading conditions on the left ventricle.


Vascular protein metabolism in the pathogenesis of hypertension.

Labelled proline incorporation into collagenous and noncollagenous proteins of aorta or mesenteric arteries was significantly increased in 70-day-old spontaneously hypertensive rats (SHR) at the early stage of hypertension in comparison with normotensive Wistar-Kyoto (WK) rats; however such an increase was not detected in 30-day-old SHR at the prehypertensive stage. Similar increases in the  proline incorporation were noted in 70-day-old renal hypertensive rats and in DOCA hypertensive rats in which hypertension had been induced similarly to that om SHR. Furthermore, the decay of the specific activity of noncollagenous and collagenous proteins was studied for 100 days after labelled proline infusion. The dacay of the noncollagenous protein activity was clearly accelerated in the heart, aorta and especially in the mesenteric arteries of SHR compared with WK. The decrease in the hydroxyproline radioactivity of the collagenous protein was significantly faster in the aorta and mesenteric arteries in SHR. These results proved the increased protein metabolism in the arterial walls in the relatively early stage of hypertension in SHR as well as in experimental hypertension, and then suggested its importance in the common pathogenetic mechanisms of hypertension.


Plasma renin and vascular complications in substrains of the spontaneously hypertensive rat, with a reference to water and electrolyte balance.

The stroke-prone and stroke-resistant substrains of the spontaneously hypertensive rat (SHR) were employed for an evaluation of possible role of reninangiotensin system and of water and electrolyte balances in inducing hypertensive vascular lesions. Serial study on plasma renin level and vascular changes did not support the hypothesis that plasma renin is a major risk factor in the development of cardiovascular complications. The high plasma renin level seen in advanced stages of hypertension appeared to be a result of severe vascular damages, indicating malignant transformation of hypertension. In this state, water turnover was enhanced without any abnormality in electrolyte balances. A possible mechanism involved in the malignant course of hypertension is discussed.


Renin inhibition by synthetic phosphatidyl and phosphorylethanolamines.

Renin inhibitory effects of about 30 kinds of newly synthesized Phosphatidyl-E and Phosphoryl-E were studied in vitro and in vivo. Among the synthetic Phosphatidyl-E, PE (SEE ARTICLE) SERies were the most potent and these were stronger than natural Phosphatidyl-E. We also confirmed that the converison from the original Phosphatidyl-E, so called prerenininhibitor, to lyso-form to exhibit renin inhibition as mentioned by Sen et al15,16 and Baggio et al.20 was not essential. But a stronger inhibition to renin was observed in PE-72, one of synthetic Phosphoryl-E analogues. PE-104, Phosphoryl-E without long fatty acid chain, was the most potent inhibitor in this study. PE-72 and PE-104 inhibited the reaction between dog renin and substrate in a competitive way. In dogs and rats, Phosphoryl-E decreased hypertensive responce and increase angiotensin I concentration induced by the exogenous renin. Hypotensive effects of Phosphatidyl-E and Phosphoryl-E were also demonstrated in renal hypertensive rats and not in normotensive rats.


Plasma catecholamine levels in the coronary sinus, aorta and femoral vein of subjects undergoing cardiac catheterization at rest and during exercise.

Plasma catecholamine (CA) levels in the coronary sinus (CS), aorta (Ao) and femoral vein (fv) were simultaneously measured in 22 patients with various heart diseases at rest and during handgrip exercise (IHG). The mean resting levels of plasma norepinephine (NE) in CS, Ao and FV were 359 +/- 49 (SEM) pg/ml, 290 +/- 27 and 234 +/- 24, respectively. The corresponding values of epinephrine (E) were 127 +/- 18 pg/ml, 186+/- 30 and 97 +/- 11, respectively. The E values in Ao were significantly greater than those in CS and in FV (p less than 0.05). IHG exercise induced an obvious elevation of plasma CA levels in every portion of the circulation studied. The mean increments of NE concentration were 81%, 54% and 67% of the resting levels at CS, Ao and FV, respectively, while IHG induced elevation of E were 70% of the resting values at each portion studied. Significant correlations were observed between individual CA concentrations in CS and in Ao, and also between those in Ao and in FV at rest. Under raised sympathoadrenal conditions, however, individual values of NE in CS failed to correlate signficantly to those in Ao and in FV, respectively. The NE output from CS was limited to only 3% and 5% of those in Ao at rest and during IHG, respectively. An actual mean increment of NE on its passing through the coronary circulation was only 2% or less of NE output in ao at both stages. It appears, thus, to be untenable that the cardiac tissue is one of the major source of circulating CA at physiological condition. From these reasons, the direct measurement of NE levels in CS may be mandatory, when plasma CA assay is designed for the purpose of studying the role of the sympathetic nerve activity in the regulation of cardiac function.


Relationship between renin secretion and renal autoregulation in the dogs.

The present investigation examined the relationship between renin release and renal autoregulation of blood flow in the anesthetized dogs. A reduction in renal arterial pressure from control pressure to 100mmHg changed neither the flow rates of all cortex zones nor renin secretion. Further reductions of renal arterial pressure to 70mmHg and 50mmHg resulted in a significant increase of renin secretion and a decrease of blood flow in the outer cortex. Intrarenal arterial infusion of acethylcholine abolished an autoregulation of blood flow and pressure reduction to 100mmHg during acetylcholine infusion resulted in a marked increase of renin secretion without any further change in afferent arteriolar resistance. Intrarenal arterial infusion of norepinephrine at a control pressure increased a renin release. However, norepinephrine infusion at reduced pressure suppressed the renin release with recovery a vascular resistance to the control level. These results suggest that the changes in the degree of blood flow and pressure in the renal afferent arterioles are not essential for the renin release, but renin release by the pressure reduction might be related to the autoregulatory capapcity of afferent arterioles in the outer cortex.


An experience in clinical application of real-time two-dimensional echocardiography.

An experience with a real-time two-dimensional echocardiographic system was presented. In this report a sagittal plane section, i.e., the section which was parallel to the long axis of the left ventricle was used. The two-dimensional section of the normal heart, mitral stenosis, interventricular septal defect (preoperatively and postoperatively), mitral prosthetic valve, pericardial effusion, and acute myocardial infarction were studied. Easy applicability, quick recording, and non-invasive nature of the procedure, make the indications widened including acutely distressed patients. We conclude that real-time two-dimensional echocardiography is one of the most promising cardiac examinations.


Serum dopamine beta-hydroxylase in cardiovascular diseases.

Dopamine-beta-hydroxylase (DBH), the enzyme responsible for the biosynthesis of norepinephrine from dopamine was assayed in the blood serum of 23 normal adults, 16 patients with congestive heart failure, 19 patients with asymptomatic ischemic heart disease, 4 patients with angina pectoris at rest, 15 patients with essential hypertension, 8 patients with essential hypotension, 5 patients with neurocirculatory asthenia, and 9 normal adults before and after the exercise test. The serum DBH activity varied within a wide range in the control population. The DBH activity increased about 16% after the exercise stress. A tendency to increase DBH activity was shown in the patients with congestive heart failure. There was no significant difference between asymptomatic ischemic heart disease, essential hypertension and normal controls. A lower value was observed in the patients of angina pectoris at rest, while a higher DBH activity was demonstrated in the patients with essential hypotension. There was no significant difference between the neurocirculatory asthenia group and the normal control group.


Syphilis and its cardiovascular complications in the elderly.

The prevalence of syphilis and its cardiovascular complications were investigated in the living population more than 60 years of age. The prevalence of positive serologic test for syphilis (STS) were 16.9% (124/736) in males and 17.1% (236/1380) in females, which were not statistically different. Aortic regurgitation (AR) was significantly more frequent in those with positive STS (9.68% in males, 5.08% in females) compared with negative STS (0.98% in males, 1.75% in females) in both sexes (p less than 0.01) and it was marked in males. AR with positive STS had a significantly lower minimal blood pressure than AR with negative STS (p less than 0.05). Calcifications in the ascending aorta were noticed in 5 out of 24 syphilitic AR. Myocardial infarctions were almost equally found among those with positive STS (1.67%) and negative STS (1.65%), and 2 out of 6 syphilitic cases were complicated by AR. The measurement of the aortic width was not valuable for the diagnosis of uncomplicated syphilitic aortitis.


Echocardiographic measurement of aortic root diameter.

One hundred and thirty patients with various heart diseases who underwent angiocardiography were studied to assess the clinical usefulness of echocardiographic aortic root diameter. The echocardiographic aortic root diameter was measured from the anterior surface of the anterior wall to the anterior surface of the posterior wall at end-diastole. A significant correlation was found between aortic root diameters measured by angiocardiograms and those by echocardiograms (r = 0.944, p less than 0.001). The aortic root diameter in normal subjects was 15 to 40 mm with a mean value of 29.0 mm. The corrected aortic root diameter by body surface area in normal subjects ranged from 10.1 to 29.5 mm/M2 with a mean value of 19.18 mm/M2. There appeared to be direct relationship between corrected aortic root diameter and the age. Echocardiography is a simple, safe, and reliable noninvasive method for estimating aortic root diameter.


Severity of coronary sclerosis in the aged: a pathological study in 968 consecutive autopsy cases.

Severity of the coronary sclerosis was estimated in a total of 968 aged cases of consecutive autopsy. Incidence of myocardial infarction was elevated in the high stenotic indices (sum of the coronary stenosis of the 3 vessels). There were 594 cases (61.4%) of balanced stenosis, 238 cases (24.6%) of unbalanced stenosis, and 136 cases (14.0%) of rare type (extreme difference of degree of stenosis between 3 vessels). There were 155 cases (16.0%) of 3 vessel disease, 154 cases (15.9%) of 2 vessel disease, 215 cases (22.2%) of 1 vessel disease, and 444 cases (45.9%) of no significant coronary sclerosis. Incidence of myocardial infarction in these 4 groups was 47.1%, 22.1%, 9.3%, and 2.3%, respectively. The left anterior descending artery was the leading artery in 1 and 2 vessel diseases, followed by the right coronary artery and then the left circumflex coronary artery.


Hypotensive action and increased plasma renin activity by Ca2+ antagonist (Nifedipine) in hypertensive patients.

The Ca2+ antagonistic coronary vasodilator, Nifedipine, was sublingually administered by a dose of 30 mg to 19 patients with hypertension. Blood pressure of patients with with essential hypertension (n=14) decreased from 177 +/- 24 to 123 +/- 13 mmHg systolic and from 108 +/- 12 to 80 +/- 11 mmHg diastolic (mean +/- SD) (p less than 0.01). Plasma renin activity (PRA) increased significantly from 0.73 +/- 0.62 to 1.50 +/- 1.02 ng/ml/h (p less than 0.05). The same tendency was observed in malignant and renovascular hypertension. In primary aldosteronism (n = 2), blood pressure decreased but PRA did not increase. Hypotensive action and increased plasma renin activity by Ca2+ antagonist, Nifedipine, were clearly demonstrated in patients with hypertension.


Influence of alpha- and beta-sympathetic blockade on hypoxic sensitivity of the coronaries.

The effect of 2 types of adrenergic blockade on the capacity of the coronaries for hypoxic dilatation was studied in open chest dogs under chloralose anesthesia. Reactive hyperemia following the temporary occlusion of the left coronary artery and the vasodilatation elicited by general arterial hypoxia served to determine the range of coronary adaptation. beta-adrenergic blockade induced by propranolol (0.3 mg/Kg i.v. or 0.05 mg/Kg intracoronarially) failed to reduce the range of hypoxic dilatation. On the other hand, the alpha-blocking agent phentolamine (0.45 mg/Kg i.v. or 0.15 mg/Kg i.c.), in association with a decrease of the vascular tone, significantly limited the coronary adaptation to hypoxia.


Phasic coronary blood flow patterns as related to the balance between oxygen demand and supply in the myocardium.

To explore possible relationship between changing coronary arterial flow patterns and states of coronary circulation, the left circumflex arterial flow (mean and phasic) was measured simultaneously with the oxygen saturation of the great cardiac vein blood (SGCVO2) in anesthetized open-chest dogs. Coronary vasomotion was altered either with administration of drugs or with mechanical interventions. The "intermittent" flow pattern observed in the resting state persisted as far as SGCVO2 remained unchanged or lowered regardless of changes in coronary flow, aortic pressure or heart rate. On the other hand, when increase in circumflex flow occurred simultaneously with elevation of SGCVO2, a "continuous" flow pattern of the circumflwx flow was noticed. We suggest that (1) the "intermittent" flow pattern would indicate that efficient O2 uptake from the supplied arterial blood is taking place in the myocardium and (2) the "continuous" flow pattern would indicate presence of arterial flow excess to the myocardial requirement, rendering the increased coronary blood flow less effective for its amount in terms of O2 supply to the myocardium.


Renin and nervous system.

The renin release is controlled mainly by 3 mechanisms which are mutually not exclusive. The mechanisms can work together or 1 mechanism may play an important role than the other 2. The 3 mechanisms are the sympathetic nervous system, intrarenal baroreceptors, and the macula densa. In this paper, the renin release by electrical stimulation of brain stem, renin release by beta-adrenergic receptor, renin release by catecholamine infusion and angiotensin=sensitive site in brain are reported and discussed.


Positive feedback hypothesis on development of essential hypertension.

A hypothesis is presented on a possible mechanism of development of the essential hypertension. The present theoretical consideration with Laplace's law and Poiseuille's law indicates that arteriolar constriction increases, unless the blood flow is reduced, both arterial blood pressure and vascular circumferential wall tension which is considered a trigger of medial hypertrophy of the constricted arteriole. If the medial hypertrophy aggravates the vascular constriction, it all the more increases arterial pressure and wall tension. Therefore, the initial arteriolar constriction, however slight, may progressively produce hypertension and augment medial hypertrophy by such a positive feedback mechanism.


Changes in P-R interval immediately before, during, and after acute myocardial infarction.

A 48 years old male developed acute cardiac pain manifested by prolonged P-R interval as the only electrocardiographic sign. Subsequently the electrocardiogram evolved an acute myocardial infarction with a normal P-R interval. Immediately therafter prolonged P-R interval reappeared to become established even after digitalis was long discontinued.


Behaviors of a vigorous protease-producing strain of Staphylocollus aureus in the skin tissue of mice.

The behaviors of a protease-producing strain of Staphylococcus aureus, including the production of alpha- and beta-hemolysin, protease, and nuclease in the skin tissue of mice, were examined by the fluorescent antibody technique and hematoxylin and eosin staining. When about 10(6) viable cells were subcutaneously inoculated into a mouse, they were phagocytized by leukocytes and a suppurative focus developed in situ. No active extracellular substances other than alpha-hemolysin were demonstrated in this mouse. When 10(7) viable cells were inoculated, most of them were also phagocytized by leukocytes, and a rather large suppurative focus was formed. In this focus a low degree of multiplication of the organisms was observed. Protease and alpha-hemolysin could be detected in the neighborhood of the leukocytes. When 10(8) to 10(9) cells were inoculated, they multiplied transitorily in the subcutaneous tissue and produced the four substances mentioned above. The multiplication of bacterial cells as well as the production of extracellular substances ceased within a comparatively short period and the transitory state was similar to that in a batch fermenter. Necrotic and histolytic lesions were observed only in the mice inoculated with 10(8) to 10(9) viable cells. Similar dermatolytic lesions were also found in mice injected with 0.5 to 1.0 mg of pure protease.


Studies on delayed hypersensitivity of antigens isolated from Mycoplasma pneumoniae cells.

Cells of Mycoplasma pneumoniae Mac strain were fractionated into acetone-soluble and insoluble fractions. Acetone-insoluble fractions were digested with pronase and further purified by chromatography on Sephadex G-75, yielding three water-soluble fractions which were free from lipid and consisted mainly of polysaccharide-protein complex. All these water-soluble fractions possessed eliciting antigenicity to delayed hypersensitivity for M. pneumoniae as measured by skin reactions and macrophage migration inhibition tests, but not to complement-fixing antibodies. In contrast, the acetone-soluble fraction was reactive with the complement-fixing antibodies but not for the delayed hypersensitivity.


The ability of athymic nude mice to survive intracerebral infection of lymphocytic choriomeningitis (LCM) virus.

Adult athymic nude mice were protected against the lethality of intracerebral infection with LCM virus. Although the multiplication of LCM virus in the brain was almost equal between nu/nu and nu/+ mice, the delayed hypersensitivity reaction was not evoked in nu/nu mice as evidenced by foot pad reaction.


Effects of oxygen supply on electrical and secretory responses of humorally stimulated acinar cells in isolated rat pancreas.

A technique is described for perfusing isolated rat pancreas with a modified Krebs-Henseleit solution. This preparation made feasible the simultaneous measurement of transmembrane potential, effective membrane resistance, rate of flow of pancreatic juice and amylase output. The hyperpolarizing effect of cholecystokinin-pancreozymin (CCK-PZ) was confirmed by perfusion with a solution containing 5 mU CCK-PZ/ml. The hyperpolarizing efffect of CCK-PZ was enhanced when the pancreas was perfused with an oxygenated solution containing dog erythrocytes. This effect was inhibited by ouabain and anaerobic conditions. It is suggested that the oxidative metabolism supplies energy for a mechanism which is responsible for the hyperpolarizing effect of CCK-PZ. The amylase output and the rate of flow of pancreatic juice were enhanced concurrently under conditions that augumented the hyperpolarizing effect, and they were inhibited under conditions that suppressed the effect. Cellular events in stimulus-secretion coupling in the pancreatic acinar cell are discussed by correlating the electrophysiological responses and the secretory responses under various conditions.


Role of superficially membrane-bound calcium on excitation-contraction coupling in frog skeletal muscle.

Single fibers isolated from frog semitendinosus muscle continued to twitch for 5-8 min in calcium-free Ringer solution containing 1 mM ethylene glycol bis (beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA). Even after twitching was completely abolished, the tension of potassium contracture was not depressed, although the time course was markedly shortened. The resting potential recorded from single fibers 10 min after immersion in EGTA-Ringer solution decreased slightly. These fibers failed to generate action potential, however, in a whole sartorius muscle the self-exchangeable calcium was not significantly reduced by 1mM  EGTA, while it was reduced by about 27% during the potassium contracture induced in the EGTA solution. From these results, it is suggested that the calcium bound on the surface sites of the transverse tubular membrane and the sarcolemma can serve as a trigger for the release of calcium from the sarcoplasmic reticulum and can produce a resting potential and maintain relatively long duration excitability under the condition of extracellular calcium deficiency.


Contracture and hyperpolarization of the rabbit sinoatrial node cells in Na-depleted solution.

A study was made on both hyperpolarization and contracture which developed in the rabbit sinoatrial node cell during perfusion with Na-depleted solution. The membrane was hyperpolarized in 19 out of 27 specimens (-69.5 +/- 6.0 mV), while in the remaining 8 specimens the value of the membrane potential remained low (-39.4 +/- 2.7 mV). Slope conductance increased as the membrane was hyperpolarized in Na-depleted solution, but not when the value of the membrane potential remained at low. The amplitude of hyperpolarization increased with decrease in Na concentration, increase in Ca concentration and increase in perfusate temperature. A marked increase in diastolic tension was observed in 23 out of 29 specimens but in the 6 remaining specimens the increase in tension was small. Tension increased with decrease in Na concentration, increase in Ca concentration, and increase in perfusate temperature. Pretreatment with ouabain caused a consistent increase in contracture tension, while its effect on the membrane hyperpolarization was variable among different specimens. These results may be explained by assuming that intracellular Ca concentration increased with Na-Ca exchange in Na-depleted solution. In addition to contracture, increase in intracellular Ca concentration might have caused an increase of membrane K conductance and produced marked hyperpolarization.


Contraction produced by intracellular injection of calcium, strontium, and barium in the single crayfish muscle fibers.

Ca ions were ionophoretically injected through an intracellular microelectrode into the single muscle fiber of a crayfish, and the resulting contraction sphere was observed under a microscope and photographed with a movie camera. The minimum contraction produced by the threshold current involved usually three or four, sometimes two, sarcomers on both sides of the injecting pipette but contraction involving only one sarcomere was not observered. The rheobase of the Ca-injecting current was 3.2 X 10(-9) A. The strength-duration curves were determined for Ca-, Sr-, and Ba-injecting currents; all fitted a similar hyperbolic equation. The threshold amount of Ca above rheobasic injection was 2.1 X 10(-15)mol, and the ratios between threshold amounts were Ca: Sr: Ba=1: 1.9: 3.0. The effects of Ca and Sr were additive for the contraction. More current was required for the Ca-injection to produce the contraction in the K-depolarized-or 15mM-procaine-treated muscle, although less current was sufficient for the muscle treated with 0.5-1.0 mM of caffeine. The participation of the Ca-induced Ca release mechanism in the contraction produced by Ca injection and the role of Sr or Ba as a substitute for Ca were discussed.


Novel action of a piperazine derivative on the end-plate of the frog.

The effects of a piperazine derivative, trimetazidine (1-(2, 3, 4-trimethoxybenzyl) piperazine dihydrochloride) on the frog end-plate membrane were studied. Action and resting membrane potentials and the input resistance of muscle fibers were not affected by trimetazidine (82-165 muM). Under these conditions, the frequency of the miniature endplate potentials was unchanged while its amplitude was slightly decreased. The amplitude of acetylcholine (ACh) potentials were markedly and reversibly decreased after application of trimetazine (82-165 muM). The dose response curve of the end-plate membrane to ACh showed a non-competitive type of blockade. Trimetazidine (165 muM) not only decreased the amplitude of the end-plate currents (EPC) recorded from the glycerinated muscles using a voltage clamp technique, but also drastically shortened its time course. Under these conditions, the falling phase of the EPC became completely voltage insensitive. The equilibrium potential for the EPC slightly shifted to a more negative value in the presence of trimetazine (165 muM). Coefficient of variation of EPC was increased by Trimetazidine (165 mum), indicating a decrease in the quantal content of the EPC. The rate of desensitization of the end-plate to ACh was facilitated and the rate of decrease in EPC amplitude during tetanic stimulation became voltage sensitive by the action of trimetazidine (133 muM). It is concluded that trimetazidine mainly acts on the postsynaptic membrane with a weak presynaptic action. The agent seems to block a step subsequent to the interaction of ACh with its receptor, which presumably involves changes in the ion conductance of the membrane and is responsible for the voltage sensitivity of the response.


Effects of diets on cold tolerance and metabolic responses to cold in fasted rats.

Effects of high-fat and high-protein diets on cold tolerance in fasted rats were investigated. High-fat diets caused significant increases in body weight, blood-free fatty acids (FFA), ketone bodies and glucose, while high-protein diet did not modify any of these parameters. Rats on high-fat diets that were exposed to cold after clipping exhibited an intermediate cold tolerance as assessed by the rate of fall in colonic temperature between control rats on a standard diet and cold-acclimated rats. The extent of increase of blood FFA and decrease of blood glucose due to cold exposure was less in the high-fat diet group than in control group, but greater than in cold-acclimated group. The lower fall in colonic temperature due to cold exposure was signifcantly associated with less increase in blood FFA and less decrease in blood glucose. In this relation the high-fat diet group was also intermediate between the control and cold-acclimated groups. The high-protein diet did not make any difference in cold tolerance and cold-induced changes in blood metabolites as compared with those in control standard diet, although it resulted in a marked increase in urinary nitrogen excretion. These results indicate that a high-fat diet could exert a significant favorable effect on cold tolerance in fasted rats, but the effect would not be as much as as in cold acclimated rats.


The effects of D600 and verapamil on action potential in the X-organ neuron of the crayfish.

The effects of D600 and verapamil on the membrane activity of the X-organ neuron of the crayfish were investigated. In TTX solution, D600 and verapamil reversibly reduced the amplitude and the maximum rate of rise of the Ca-dependent action potential as well as delayed rectification. The decrease and the recovery in amplitude of the Ca spike were usually accompanied by parallel changes in delayed rectification. The threshold concentration for observable effects on the Ca spike was from 5 X 10(-6) g/ml to 1X 10(-5) g/ml for both drugs. At 1 X 10(-4) g/ml, the Ca spike was almost blocked. The dose-response relation  with regard to the maximum rate of rise of the Ca spike showed no noticeable difference in effect between D600 and verapamil. By increasing the extracellular Ca concentration, the Ca spike, which had been reduced by these drugs, was restored by the delayed rectification remained to be reduced. In Mn solution, both D600 and verapamil reduced the amplitude and the maximum rate of rise of the Na-dependent action potential as well as the delayed rectification. At 1 X 10(-4) g/ml, the maximum rate of rise of the Na spike was reduced by 30 to 50% with each drug. From the experiments in the Ca and the Mn solutions, it was inferred that the decrease in K activation by these drugs was not brought about secondarily by the decrease in Ca activation but both activation were inhibited independently. It was concluded that both D600 and verapamil are the inhibitors for Ca activation in the X-organ neuron of the crayfish, although they are not Ca specific.


[Disorders of intraventricular conductivity in ischemic heart disease].

An analysis of 439 cases of interventricular blocks in ischaemic heart disease is presented, 75.2% of the disorders developing in the branches of the left His' bundle. Intraventricular block was more common in cases of large focal myocardial changes. Bifascicular blocks preceeded full atrioventricular block more often than other forms of intraventricular conductivity dosorders. The greatest difficulties were encountered in the electrocardiographic diagnosis of focal changes in the posterior wall of the left ventricle when the left anterior branch of His' bundle was blocked.


[Discriminative analysis in detecting cardiac insufficiency in myocardial infarct on the basis of the values of stroke volume and blood lactic acid level].

In 203 patients with large focal and transmural myocardial infarctions the cardiac output was studied by means of the dye dilution method, as well as the content of the lactic (Barker and Summerson's technique) and pyruvic acids (Travina's technique). Along with the growth of cardiac insufficiency a fall was observed in the cardiac and stroke indices, and a growing content of the lactic and pyruvic acids and of the L/P factor. The stroke index and the blood lactate level proved to be the most informative values. With a stroke index below 24 ml/m2 all patients with myocardial infarction displayed signs of cardiac insufficiency, while with a stroke index above 54.2 ml/m2 cardiac insufficiency was lacking. A stroke index falling between 24 and 54.2 ml/m2 was observed in both the patients with cardiac insufficiency, and in those without it. A lactic acid content above 31.8 mg% was always concomitant with cardiac insufficiency. With the lactic acid level ranging from 16 to 31.8 mg% the probability of cardiac insufficiency was doubtful.


[Strophanthin sensitivity of animals after coronary artery occlusion and pharmacological action on adrenergic innervation of the heart].

In 95 feline experiments it was established that coronary artery occlusion does not affect the Strophantin lethal dose, but it increases the sensitivity to the arrhythmogenic effect of the cardiac glycoside after 24-48 hours. Premedication of intact animals with such a beta-adrenergic blocking agent as Anapriline (Inderal) significantly increases the toolerance of Strophantin while the stimulation of the beta-adrenergic structures with Isadrine, on the contrary, decreases the arrhythmogenic and lethal dose of Strophantin. In coronary circulation disorders the pharmacological block of the adrenergic heart innervation did not produce any significant reduction of the sensitivity to the cardiac glycoside.


[Study of the relation between cardiac function and the tonus of resistant vessels in experimental disorder of coronary circulation].

In tests set up on dogs under morphine-chloralose anesthesia features specific for upset cardio- and hemodynamics following a primary and repeated (against the background of a preliminarily provoked myocardial infarction) acute disruption of the coronary circulation were investigated. The development of an acute ischemia of the myocardium in animals with preliminarily induced chronic disruption of the coronary circulation was shown to be attended by more intensive than in healthy dogs hemodynamic shifts and functional disorders of the heart, whereas the reflex component of the reaction, the vasodilating reactions of the peripheral vessels, in particular, proved much less marked. Possible mechanisms accounting for differences in the derangement of the cardio- and hemodynamics in primary and repeated ischemia of the myocardium are discussed.


[Myocardial changes in rats after considerable physical exertion and the effect of pyridoxilate on the severity of these changes].

Under significant physical exercises the myocardium of rats displays distinct enzymopathy, increased permeability of the cell membranes with a considerable dispersion of plasma proteins and damage to the ultrastructures of the myocytes. The employment of pyridoxilate reduces the severity of the damaging reaction, and to some extent normalizes the structure of the cellular and sub-cellular elements of the myocardium. This indicates to the prospects of using the regulators of cellular respiration under total and tissue hypoxia.


[Lipid peroxides and arteriosclerosis].

The significance of free radical oxidation of phospholipids in tissues of animals with experimental atherosclerosis was investigated. By using modern physico-chemical methods an elevated content of polyunsaturated fatty acids and other lipids peroxides was discovered in the blood and the aorta of rabbits with experimental atheromatosis. The human blood demonstrated a low level of protective enzymatic systems and a high content of products secondary to peroxidal oxidation of the lipids. The mechanism accounting for the action of lipids peroxides on the vascular wall resulting in the formation of atheromatous plaques is considered.


[Mechanism of lipoprotein and cholesterol transport into the vascular wall].

Penetration of radioactive lipoproteins of very low and low density, of free cholesterol and its esters into the aortal wall of rabbits was studied. Close values for ratios between lipids and protein, cholesterol and esterified cholesterol contained in the perfusate's lipoproteins and corresponding lipoprotein fractions separated from normal and atherosclerotic aortas following their perfusion were registered. These findings bear evidence to the fact of atherogenic lipoproteins penetrate the vascular wall in the form of intact particles. Quantitative regularities educed in this connection point to a greater permeability of atherosclerotic aortas to lipoproteins. An analysis of aortal lipids uncombined with lipoproteins showed the ratio between cholesterol and etherified cholesterol to be on the average 5.5 times as high as in the lipoproteins of the aorta and the perfusate. The prevalence of cholesterol in the lipids of the aortal tissue uncombined with lipoproteins points to the existence of other mechanisms governing the entrance of radioactive cholesterol into the vascular wall. Tests in vivo involving intravenous administration of C14-cholesterol yielded the same regularities as "in vitro" experiments.


[Role of foam cells in lipoprotein transformation within the vascular wall].

Foam cells were isolated from atherosclerotic aortas of rabbits following their intima incubation with collagenase and elastase. The viability of the cells, their incidence and nativity were supported histochemically and electron-microscopically. The interaction of the foam cells with lipoproteins was studied in vitro with perfusions of isolated atherosclerotic aortas of rabbits during 6 hours with a medium containing beta- and pre-beta-lipoproteins labelled with I125 or simultaneously with I125 and C14-cholesterol. It was found that after the perfusion the foam cells contain a much higher proportion of radioactivity of the total lipids, cholesterol and cholesterol esters, to that of the proteins, than the perfusate. The foam cells must selectively "capture" the lipids from the lipoprotein particles. The proportion "free cholesterol/cholesterol esters" (according to the radioactivity) proved to be much higher in the foam cells than in the perfusate. The possible mechanisms of the participation of the foam cells in the metabolism of lipoproteins and in the pathogenesis of atherosclerosis are discussed.


[Free hydroxyproline content of the blood serum in patients with coronary arteriosclerosis].

In 47 patients with atherosclerosis of the coronary arteries the concentration of the blood serum free oxyproline was up by comparison with the normal figure and it depended not so much on the stage of the disease, but rather upon the character of hyperlipoproteinemia. A higher oxyproline concentration was revealed in the blood serum of patients presenting the IIb and IV types of hyperlipoproteinemia. The results of experimental investigations suggest that the activation of the glucocorticoid function of the adrenal cortex in patients with atherosclerosis of the coronary arteries results in a more intensive catabolism of the vascular wall collagen and in attending it rise of the blood serum free oxyproline concentration.


[Various changes in the composition of blood serum phospholipids and lipoproteins in arteriosclerosis].

The composition of phospholipids of plasma lipoproteins was studied in normal individuals and in patients with coronary atherosclerosis with type IIb and IV hyperlipoproteidemia using two-dimentional thin-layer chromatography. It was demonstrated that in normals the fractions of lipoproteins of a very low, low and high density have an even distribution of most of the phospholipid components, lecithin and sphyngomyelin being the prevailing phospholipids in all fractions of lipoproteins. In type IIb and IV hyperlipoproteidemia, lipoprotein fractions of very low density have a relatively elevated content of lecithin and those of high density have an elevated content of lecithin and lysolecithin and a decreased level of sphyngomyelin. The obtained data are discussed in terms of the possible effect of the chemical composition of phospholipids on the properties of lipoproteins in atherosclerosis.


[Lipid content of the blood serum in relatives of patients with ischemic heart disease].

The method of calculating the threshold levels of blood plasma cholesterol and triglycerids was analysed. The threshold levels were used for a genetic analysis of the relatives of the probands with coronary heart disease combined with hyperlipoproteinemia. Among 25 relatives of probands suffering coronary heart disease combined with hyperlipoproteinemia the latter was found in 15, while among 25 relatives of probands suffering coronary heart disease and having normal lipid levels hyperlipoproteinemia was found only in 2. The presented data characterise the peculiarities of the diagnosis of familial (primary) hyperlipoproteinemia and support the importance of the hereditary factor in the regulation of lipid metabolsm in the families of coronary atherosclerosis patients.


[Plasma renin activity in patients with coronary arteriosclerosis with different types of hyperlipoproteinemia].

The examination was conducted in 142 patients with coronary atherosclerosis, aged 33 to 74 years, and in 40 normal persons, aged 25 to 48 years. The pain form of the disease was observed in 96 patients, the arrhythmic one--in 38, the painless one--in 8 patients. The arterial pressure was within the normal limits in the examined patients. In 67.6% of the patients hypercholesterolemia was diagnosed, in 47.3%--hypertriglyceridemia. Type II hyperlipoproteinemia was found in 67.6% of the cases, types III and IV--in 5.3 and 9.1%, respectively, type V--in 0.5% of the patients; the type of hyperlipoproteinemia could not be identified in 10.6%, and in 6.9% of the cases the blood level of lipoproteins did not differ from the normal. The plasma renin activity examined by the radioimmunoassay in normals comprised 1.26 +/- 0.21 ng/ml/hour; in patients with the pain form of coronary atherosclerosis--6.67 +/- 0.72 ng/ml/hour; in those with arrhythmias--6.89 +/- 1.20 ng/ml/hour; in those with the painless form--2.39 +/- 1.02 ng/ml/hour. The highest renin activity was revealed in types IIa, IIb and III hyperlipoproteinemia, as well as in paroxysmal arrhythmia and cardiac fibrillation.


[Quantitative composition of blood plasma prostaglandins in patients with ischemic heart disease].

From the blood plasma of 34 patients with ischemic heart disease and hyperlipoproteinemia and without it and in 10 practically healthy persons prostaglandins E, A and F2alpha were isolated and the proportion of each one of them was determined by the radioimmunological method. Changes in the quantitative composition of the blood plasma prostaglandins in patients with ischemic heart disease and hyperlipoproteinemia were disclosed, these changes suggesting the participation of the substances in question in the pathogenesis of atherosclerosis.


[Diagnostic possibilities of veloergometry in ischemic heart disease].

The results of a veloergometric investigation of 160 persons, most of whom were patients with ischemic heart disease, are analyzed. The method of graded physical loads is a necessary complement and continuation of clinical and instrumental examination of patients afflicted with ischemic heart disease. A key electrocardiographic indication of coronary insufficiency identifiable following physical loading is a shift of the ST segment. This sign helps disclose the presence of latent coronary insufficiency in most patients with typical angina pectoris and in 25 per cent of patients with an atypical form of this ailment. In some of the patients with ischemic heart disease the results of the test can be utilized in recognizing early stages of cardiac incompetence. A feature distinguishing the response to a physical load in patients with ischemic heart disease is a greater accretion of systolic pressure than in the case of healthy individuals.


[Various aspects of the pathogenesis of arteriosclerosis in the light of data of geographic pathology].

An analysis of 9.550 autopsies of males, aged 10 to 69 years, demonstrated that the time and incidence of the appearance of lipid spots did not depend on the place of residence and ethnic characteristics of the person, while the appearance and further progressive development of fibrous plaques and other more severe kinds of atherosclerotic changes varied greatly from one geographic zone and ethnic group to other. The results of the study of different stages of atherosclerosis and the analysis of literature data support our earlier concept that indicates that fibrous plaques do not necessarily develop from lipid spots, and the latter do not necessarily transform into fibrous plaques.


[ECG changes during an attack of stenocardia caused by physical exertion].

In 85 patients suffering from ischemic heart disease ECG changes appearing at the time of an attack of angina pectoris provoked by a physical effort were studied. An analysis of these changes helps substantiate an objective choice of criteria for stopping a physical load test in this category of patients. As shown by pertinent investigations there is good reason for broadening the criteria for cancelling the load test in persons with a manifest coronary incompetence. A complete scientific justification of criteria for cancelling tests involving physical efforts is possible through contrasting the described changes against coronarographic, clinical and catamnestic findings.


Water extraction from the inner medullary collecting tubule system: a role for urea.

Recent examinations of the inner medullary collecting tubule membrane in vitro have demonstrated that its reflection coefficient to urea (sigma urea) is significantly less than unity and less than sigma NaClhe presence of antidiuretic hormone. Fluid entering the inner medullary collecting tubule has a higher urea concentration and lower NaCl concentration than does the medullary interstitium, although total osmolarity is nearly equal on either side of the membrane. The transtubular difference in solute composition, together with the difference between sigma urea and sigma NaCl, should result in a driving force for extraction of water from the tubule. This hypothesis was examined in a differential analysis of water and solute fluxes across the collecting tubule epitheliu. The results indicate that this driving force contributes significantly to water extraction from the inner medullary collecting tubule.


Mineralocorticoid and glucocorticoid receptors in human kidney.

Currently, studies on renal mineralocorticoid and glucocorticoid receptors have been confined to experimental animals. In experiments made upon human kidneys removed at operation, tritiated aldosterone has been shown to bind specifically to a single class of cytoplasmic sites which show steroid specificity requisite for physiological mineralocorticoid receptors. Tritiated dexamethasone, similarly, binds specifically to a single class of cytoplasmic sites with affinity characteristics appropriate for glucocorticoid receptors. The similarity between the human renal receptor profile for adrenocorticoids and that found in experimental animals may validate cautions extrapolation from animal models of adrenocorticoid effector mechanisms to man.


The role of volume contraction in the hypocalciuric action of chlorothiazide.

Thiazide-induced hypocalciuria usually requires two to four days of drug treatment for its full expression. The present experiments were designed to test the possibility that an immediate hypocalciuria could be produced in subjects whose extracellular volumes were already contracted. In previously untreated subjects, chlorothiazide (2 g/day) did not produce hypocalciuria on the first day of treatment. Hypocalciuria occurred on the second day and was somewhat enhanced on the third and fourth days of treatment. In subjects pretreated with furosemide (40 mg two or three times a day for two days), chlorothiazide produced hypocalciuria on the first day of its use. Under the influence of chlorothiazide, there was a strong linear correlation between the changes in the excretion of calcium and sodium. The results are consistent with the idea that chlorothiazide enhances the ratio of calcium to sodium reabsorptions and that this tendency for absolute hypocalciuria can be overridden by a large natriuretic response to the drug. Volume contraction, which minimizes the natriretic response to diuretics, allows a more immediate and pronounced hypocalciuric response to thiazides.


[Bull's-eye disease (author's transl)].

Bull's-eye disease is observed in all degenerative maculopathies whether hereditary or acquired, whether primary or secondary, which have as cause an elective or obvious pigment-cell condition. In evolutionary maculardegeneration is bull's-eye disease a temporary occurrence, which precedes the diffuse depigmentation of the macular pigmentepithelium.


[Clinically unsuspected malignant melanomas of the posterior uvea (author's transl)].

Out of 1300 eyes enucleated between 1966-1974, 300 subsequently revealed histologically-proved malignant melanomas of the uvea. In 264 cases the clinical diagnosis was correctly made. In 36 cases the i.o. malignant melanomas were clinically unsuspected. The incorrect clinical diagnoses included: secondary glaucoma (30), retinal detachment (2), iritis (2), and end/panophthalmitis (2). The clinical symptomatology and morphology of the secondary glaucoma caused by the i.o. melanomas did not differ from that due to other, non-neoplastic etiologies. In almost all of the 36 cases the eyes revealed unilateral severe opacity of the media. It is important that one consider an intraocular melanoma in cases of secondary glaucoma, retinal detachment, or intraocular inflammation in which the etiology is uncertain. This is also true in cases of blind, painful eyes in which there is no obvious etiology. Early diagnosis is of vital interest to the patient because this group, in which the malignant melanoma was unsuspected, may be, as suspected in this study, is characterised by extreme aggressivness and invasive capacity. One third of these eyes revealed extension of tumor through the sclera and optic nerve. Also these tumors often revealed more malignant cell types.


[Tonography after trabeculotomy (author's transl)].

In 25 eyes suffering from primary open angle glaucoma the facility of outflow was measured before and 1 to 3 months after surgery in consideration of the rigidity. Trabeculotomy improved the facility on an average of 0.14+/-0.02 to 0.28+/-0.03 units. This means that the outflow resistance is decreased from 10.58+/-1.34 to 4.31+/-0.45 units. The statistically highly significant improvement of the outflow conditions must be a consequence of the surgical opening in the trabecular meshwork as the sclera had been closed watertightly at the end of the trabeculotomy. The coefficient of rigidity (graphically determined by applanation tonometry and Schiötz tonometry in recumbent position) was decreased from 0.0208+/-0.0010 to 0.0172+/-0.0008. This means that measuring the intraocular pressure postoperatively with a Schiötz tonometer results in data which are 3.08+/-0.65 mm Hg lower than the actual pressure level.


[Hydrophthalmia and configuration of the optic disc (author's transl)].

Three sisters, one brother, and the father of a female patient with primary hydrophthalmus on both eyes had abnormally great physiologic cups. The cup/disc ratio was between 0.5 and 0.72. Two other brothers showed a cup/disc ratio between 0.37 and 0.42, whereas the mother had a cup/disc ratio of 0.2 on both sides. The enlarged physiologic cups of the sisters, the brother, and the father of the propositus correspond to the 4th category of the classification according to Elschnig. Like the hydrophthalmus as a result of a functional disturbance of the eye cup, the occurrence of abnormally big physiologic cups is also referred to the organizing and forming effects of the eye cup. Whether there exists an intrafamiliar relationship between the hydrophthalmus and the abnormally big physiologic cups or not is to be elucidated by further investigations.


[The influence of a metabolic stimulator on the vitality of preserved human corneas (author's transl)].

20 human donor corneas were placed in a tissue culture medium (TC 199 + 5% Dextran = MK-Medium) at +4 degrees C for 5 and 7 days. After that the temperature reversal effect was measured and the corneal endothelial cells were stained. The living cells were counted every 24 hours until no more cells could be seen. Another group of 20 human donor eyes were placed in to the same medium with a additional content of 5% Actihaemyl resp. Solcoseryl. Same procedure as above. It could be shown that under the influence of the metabolic activator 22.0% and 23.3% more living endothelial cells could be counted and that the total survival time could be prolonged by 1 1/2 days.


[Distraneurin (Chlormethiazol) as an anaesthetic for high-risk cases in ophthalmology (author's transl)].

A new anaesthesia, through Chlormethiazol i.v. is described, which is especially used in cataract (lens) operations. There is no excitation during induction and the depth of anaesthesia (stage) depends on dosage-time ratio. Recovery is calm without undesirable side-effects. The intraocular pressure is significantly diminished during anaesthesia.


[Cataract during intermittent hemodialysis. The influence of hypocalcemia on the development of opacities (author's transl)].

Twenty uremic patients on intermittent hemodialysis were followed up for lens changes over 4-53 months. Only one patient of 22 years with megaureters and megacystis developed bilateral anterior and posterior subcapsular cataracts during dialysis treatment. The morphology of these cataracts was similar to that of fresh hypocalcemic opacities. The patient had actually been hypocalcemic before the onset of the opacification. Possible reasons for the development of hypocalcemic cataracts during intermittent dialysis might be: 1. a reduced calcium-phosphate ratio due to phosphate accumulation, 2. a decrease of ionized calcium due to removed metabolic acidosis, and 3. a permissive effect of longer latencies.


[The influence on the speed of epithelialisation of rabbit's eyes of IDU- and tromantadine-containing eye ointments (author's transl)].

The viro-static drugs IDU and tromantadin were tested in view of their influence on epithelial regeneration. IDU slows down the speed of epithelisation only slightly, and produces no irreversible damage in the corneal stroma, Descemet's membrane and endothelium of the rabbit eye. Tromantadin, however, slows down the speed of epithelisation quite a lot, even if the dosis is relatively small. We also found substantial changes in corneal stroma and Descemet's membrane, which have been partly recognized histologically as fibrous tissue. Application of these medicaments is recommended only if the relation between side effects and viro-static potency has been carefully rated.


[Physical symptoms in the orbit during ophthalmodynamography (author's transl)].

Analysing physical process occurring in the orbit during ophthalmodynamography the author comes to the conclusion that the "systolic pressure" as recorded ophthalmodynamographically is not a real pressure present in the ophthalmic artery, but a sum of this pressure and of that which is necessary to overcome the resistence of the orbital tissues. A considerable influence of the blood flow in the system of the external carotid artery is explained by superficial localisation of arterial branches belonging to the system and consequently by direct transmission of volume and pressure changes in the blood flow to the registering device, practically without damping effect of the orbital tissues.


[The two-way syringe. A comparison to modified aspiration methods in cataract surgery, and more recent indications for its use (author's transl)].

After description of construction, indication, and application of the two-way syringe in cataract surgery, this instrument is compared to some of its numerous modfications. The original device has the advantage of simplicity, and enables the surgeon to perform simultaneous irrigation and aspiration under zero pressure conditions without an assistant. More recent indications for the use of the two-way syringe are vitreous prolapse, and retinal detachment. These operations are described in detail.


[Diabetes mellitus--not an aetiological factor of uveitis? (author's transl)].

Out of 103 patients with uveitis, 14.5% of the cases showed pre-clinical diabetes mellitus. This number exceeds by far the average frequency of approx. 6% of pre-clinical diabetes. On account of these findings, the diabetes mellitus is assumed to be a co-factor of the development of uveitis. In order to clarify the cause of uveitis, the glucose tolerancetest should be given preference in the diagnosis.


[The clinical picture, fluorescence angiography and histologie of a ringmelanoma of the iris (author's transl)].

Report on a rare case of an iris-ringmelanoma. Arising from the iris base the primary tumor spread in a continuous line along the anterior chamber angle and a shedding of tumor cells in other places of the iris surface could be stated as well. A unilateral dark spotted colouring of the iris with a secondary glaucoma was clinically observed. Gonioscopy, diaphanoscopy, 32P-test, and iris fluorescence-angiography aided the diagnosis. Fluorescence angiography appears to be of particular value in the diagnosis of malignant melanoma of the iris: The peculiar filling pattern seen at the pupillary border of the tumor has up to now only been found in malignant processes of the anterior uvea. The clinical tentative diagnosis of malignant ringmelanoma of the iris, could histopathologically be verified.


[A case of healed orbital phlegmona of sinus origin (author's transl)].

In the etiology of the orbital phlegmona the initial focus originates most frequently in the sinuses. In our case we had the opportunity to observe an orbital phlegmona caused by a purulent inflammation of the sinuses by streptococcus pyogenes (hemolyticus). The course of the process was explosive, with toxic symptoms. After a successful operation and conservative treatment, recovery was achieved.


[Fibrosarcoma of the orbit (author's transl)].

During a period of 8 months a capsulated orbital tumour--not adherent the orbital walls or the bulbus--developed in a 21-year-old female patient. The tumour was exstirpated in toto. The histological findings show a fibrosarcoma with poorly differentiated cells, giant cells and numerous mitoses. The comparatively small incidence of the tumour as well as the prognosis quoad vitam are discussed.


[Ocular myasthenia caused by D-penicillamine (author's transl)].

This report concerns a 55-year-old woman who developed ocular myasthenia after 12 months treatment with D-Penicillamine for her rheumatoid arthritis. In the last 2 years the literature contains reports of 22 similar cases.


[Stimulus deprivation amblyopia (author's transl)].

36 patients who had unilateral occlusion early in life were examined. Only 1 deprivation amblyopia due to unilateral occlusion during 9 weeks was found. Deprivation amblyopias did not occur after unilateral occlusion for periods up to 10 days.


[The correction of labile metamorphopsias with cylindrical lenses (author's transl)].

The author describes a procedure for correction of labile i.e. reversible metamorphopsias by means of cylindrical lenses. The possibility of a curative effect by long-time application of an adequate correction is discussed.


[Observations on long term medication with atropine eye-drops (author's transl)].

It is reported on two children which had moderate general symptoms after long term application of atropine eye-drops. This was observed the day after discontinuing this medication. The symptoms of nausea, vomiting and perspiration were similar in both children and disappeared after one day. The reason for the symptoms is discussed and it is warned against an excessive application of atropine eye-drops.


[Spontaneous healing of central-vein-thrombosis in early gravidity (author's transl)].

The author reports on spontaneous healing of central-vein-thrombosis of both eyes in gravidity (Mens III). The 24-years-old patient is still healthy.


[Sclerodermie en coup de sabre with spontaneous filtering bleb (author's transl)].

In a 43-year-old female patient with sclerodermie en coup de sabre on the right forehead, the following changes of the right eye were observed: Partial lack of hairs of the eyebrow; distortion of the upper eyelid, similar to a coloboma; paralysis of the inferior oblique and the superior rectus muscles; decrease of corneal sensibility; formation of a spontaneous filtering bleb in the upper limbal region; ocular hypotension with changes of the papilla.


[Remarks concerning the neuroparalytic keratitis (author's transl)].

A brief reminder is given of the antagonism between cellular pathology (Virchow) and the pathology of relation (Ricker), as well as a reference to the American paper on the "Systems of material transport in nerve fibers" by Sidney Ochs.


[A training device for intraocular surgery (author's transl)].

Description of a new holder for experimental intraocular surgery on human autopsy eyes. Stability of shape and position of the experimental eyes is achieved by a vacuum surrounding the posterior segment.


[Excision of the ciliary-body in cases of secondary closed-angle glaucoma (author's transl)].

Six cases are reported, in which an excision of the ciliary-body has been performed: 5 cases with secondary closed-angle glaucoma, and one case with secondary open-angle glaucoma. All eyes were aphakic, and in all cases other surgical interventions preceded. The ciliary-body excision is the easiest exactly doseable procedure, compared with other procedures regarding the ciliary-body. Usually excision of the ciliary-body represents the last choice to offer, however in selected cases it might be the method of choice. In this aspect our results are encouraging. The technical details of this procedure are described.


[Phacolytic and hemolytic glaucoma (author's transl)].

Clinical and histological data of four patients with acute secondary open-angle glaucoma are described. These included two hemolytic and one phacolytic glaucoma. Another patient showed a transition of hemolytic to a hemosiderotic glaucoma. The hemolytic glaucoma follows a hemorrhage of the vitreous, it is characterised by an open-angle with red-brown pigment deposits on the trabecular meshwork. Macrophages can be isolated from the aqueous humor by zentrifugation. The same macrophages and fragments of lysed red blood cells are histologically visible in the vitreous as well as in the anterior chamber and the trabecular meshwork. The cause of the large vitreous hemorrhage is often a retinal detachment. The hemolytic glaucoma must be clearly distinguished from hemosiderotic and neovascular glaucoma. A transition from hemolytic to hemosiderotic glaucoma is possible. The simultaneous description of hemolytic and phacolytic glaucoma follows by reason of the same pathogenetic mechanism. The treatment of hemolytic glaucoma follows the standard medical therapy of glaucoma. If this therapy will be unsuccessful, a paracentesis with irrigation of the anterior chamber may be required. The only therapy of phacolytic glaucoma is immediate intracapsular cataract extraction.


[Echography of the vitreous body in case of aphakia and malignant aphakic glaucoma (author's transl)].

The senile destructions of the vitreous body which can be seen with the slit-lamp (formation of visible fibres, vacuoles and posterior vitreous detachment) cause, if sufficiently advanced, small echoblips visible at echographic examination. We reexamined aphakic patients who had no complications during cataract cryo-extraction. In aphakic eyes without postoperative vitreous prolapse into the anterior chamber the echograms usually consisted of uninterrupted series of small amplitude echoes in the vitreous area. In aphakic eyes with postoperative vitreous prolapse into the anterior chamber echo-free parts were found in the vitreous area and also parts showing closer placing of vitreous echoes. The echo-free parts may represent fluid-filled vacuoles. In malignant aphakic glaucomas, which could not be controlled otherwise, we succeeded inaspirating aqueous humour from these echo-free parts by punction. Echography facilitated, in this way, the punction of the trapped aqueous. Echography of the senile vitreous destructions approaches the limits of present ultrasonographic facilities; artefacts may occur, and technical improvements are desirable and possible.


[Computer tomography in ophthalmology (author's transl)].

The computer-aided tomography system (EMI-Scan) represents a new X-ray method in neuroradiology. Some cases of various space occupying retrobulbar orbit processes are presented, and it is demonstrated that this method is also well suited to the diagnosis of orbit diseases. Physicotechnical basis, technique of examination, the indication for computer tomography and the diagnostic possibilities are described.


[Computer tomography of the eye and the orbit (author's transl)].

Princips of computer tomography is demonstrated and the absorption coefficients of ocular and orbital tissue are calculated. The advantages and disadvantages of this procedure are discussed. 39 patients with ocular and orbital diseases were examined by computer tomography. The main indication was tumors, including metastases and diseases arising from ethmoidal cells. Vascular anomalies and tumors were better demonstrated by angiography. Dislocated lens, enlarged tumors of the choroid and prostheses (cerclage and orbital implants) are demonstrable. In contrast to echography, the computer tomography gives certainly better results in the posterior part of the orbit. Technical improvement of the apparatus could lead to a wider use in ophthalmology.


[On iris reposition in case of extraction of lens (author's transl)].

A description is given of a pair of iris retractors which avoid certain shortcomings of other instruments or of other methods of retracting the iris in connection with cryo-extraction, particularly in case where the pupil cannot be dilated or only insufficiently. This pair of iris retractors has proved useful. In addition, information is given about our own technique to achieve a round functional pupil, after complicated lens-extractions with vitreous prolapse, by peripheral iridotomy parallel to the limbus and discission of the body.


[Siderosis of the lens (author's transl)].

Incipient siderosis of the lens is reflected by an extremely fine granular, almost homogenous closely subcapsular brown discoloration between the anterior capsule of the lens and the epithelium. Advanced siderosis of the lens leads to subcapsular "rust spots" of varying size, especially in the region below the pupil; to increasing permeability cataract with protein breakdown and also to brown discoloration of the developing hollow spaces and clefts containing protein. In extensive siderosis of the lens, there was the following histological evidence of iron infiltration colour reactions: Between epithelium and capsule: (fusiformly) changed epithelia, intercellular substance formed by metaplasia of epithelia with connective tissue fibrillae (birefractive capsular cataract), in large, balloon-like epithelial cells freely occurring in the liquefied capsule, by decomposition of these cells in all fluid cavities containing protein (water clefts, etc.). On the other hand, there were no siderous granulations of protein: in normal epithelial cells of the lens, in unchanged fibres of the lens, in Wedl's cells and in Morgagni's or myelin droplets.


[Corneal pathology in rheumatoid arthritis and Sjögren-syndrome with special reference to "rheumatoid keratomalacia" (author's transl)].

The corneal pathology in rheumatoid arthritis and Sjögren's syndrome is described with emphasis on rheumatic keratomalacia. This particular disorder whether affecting the central and paracentral or the peripheral parts of the cornea is characterized by thinning of the corneal stroma, loss of epithelium, ulceration and eventually by corneal perforation. 7 cases are reported. Reduced tear production and simultaneous corticosteroid treatment seem to be the essential pathogenetic factors of this corneal disease. Therapeutic consequences and differential diagnosis are discussed.


[Combined contactoptical system (author's transl)].

The indications and the adaptation method of a combined contactoptical system called piggy-back system, are dealt with. This system comprises the adaptation of a soft contact lens on which is applied afterwards, a hard one. The optical and the therapeutic results obtained in 7 groups of patients (56 eyes) with astigmatism, aphakia, keratokonus, keratoplasty, injuries, chronic lesions of the epithelium, and hyposecretion of the tear fluid, are discussed together with the results of the adaptation of the lenses.