Endolymphatic sac drainage in Meniere's disease. Endolymphatic sac drainage was applied in 7 cases of severe Meniere's disease. The results were favorable in 4 patients, while 3 patients had insufficient relief. The management of Meniere's disease is discussed in relation to surgery.


Bromide partition test in the evaluation of the blood-cerebrospinal barrier in children with congenital hypothyroidism and central nervous system disease. Serum and cerebrospinal fluid bromide partiton was studied in 11 children with congenital hypothyroidism, in 12 children with tuberculous meningitis, and in 10 children with various neurological disorders. The ratio serum bromide per cerebrospinal fluid bromide (bromide index) was below the critical value of 1.65 in 5 of 11 children with hypothyroidism as compared with 10 of the 12 children with tuberculous meningitis. No clear correlation was found between the test and the clinical and laboratory signs of hypothyroidism. The test is a valuable index of blood-cerebrospinal fluid barrier involvement in hypothyroidism.


Sugar metabolism in obese children.

Sugar metabolism in obese children. In obese children the glucose tolerance curve results in high blood sugar values. A pathologic rise of the serum insulin level may occur even with normal blood sugar curves and the insulin levels tend to be higher in obesity of long standing. In obese children of families with diabetes, post-loading insulin levels were comparatively lower. It is suggested that this weaker insulin response is related to a prediabetic state.


Leukocyte migration inhibition by a brain tissue antigen and electroencephalography in uncomplicated measles. In 11 patients with uncomplicated measles and in 10 control patients with acute enteritis, electroencephalography and leukocyte migration inhibition test using basic myelin protein as antigen were carried out. There were no EEG abnormalities and no migration inhibition in the control group. Leukocyte migration inhibition was observed in 9 measles patients; among these 5 had slight or moderate EEG abnormalities. It is suggested that EEG abnormalities have the same pathological background in uncomplicated measles as in measles encephalitis.


Influence of maternal thymectomy on development of the offspring in the rat. Average body weight of the offspring of thymectomized mother rats is significantly less than normal at the age of 17-20 days. At other ages the difference is less pronounced. Though the mortality rate of such offspring seemed to be doubled, the difference was not significant. As compared to the controls, the sham operation itself decreased the thymus weight.


Bactericidal capacity of plasma and granulocytes in small-for-dates newborns. The bactericidal activity of plasma and granulocytes as measured against a Staphylococcus aureus strain was significantly lower in small-for-dates than in normal newborn infants.


The concentration of invidual monocarboxylic short chain fatty acids in serum of normal children. The normal serum concentrations of short-chain fatty acids C2--C6 (acetic to n-caproic) were estimated by gas chromatography in 35 children aged 4-16 years. Individual fluctuations were wide. The highest mean level concerned acetic acid (6.98 +/- 3.71 mug/ml), whereas the mean concentrations of other SFA were considerably lower and did not exceed 1.0 mug/ml except for n-caproic acid (1.34 mug/ml).


Monocarboxylic short-chain fatty acids C2-C6 in serum of obese children. The serum concentrations of monocarboxylic short-chain fatty acids (acetic to n-caproic) were estimated in 12 children with simple obesity aged 4-16 years and in a control group of 35 normal subjects. In the obese patients, significantly decreased values for acetic and n-caproic acid and an increased total free fatty  acid level were found. The presumable causes of the phenomenon are discussed.


The partition of maintenance energy expenditure and the pattern of substrate utilization in intrauterine malnourisheed newborn infants before and during recovery. Total heat production and its major components, as well as the pattern of substrate utilization were measured by indirect calorimetry during a period of several hours in 15 small-for-gestational-age infants between the 2nd and 15th postnatal day (non-growing period) and between 16th and 39th day (growing period). 1. Mean total heat production of the non-growing infants did not exceed 50 Cal/kg/24 hrs. Mean basal metabolism in this period was not higher than that reported for premature infants of similar body size and postnatal age. It is concluded that the caloric input necessary to meet the cost of maintenance was less than that calculated from the components of energy metabolism. 2. Total energy expenditure was significantly higher in the growing period, and its partitioning showed that all the three components (basal-, resting-, and activity metabolism) were contributing to the increment. 3. The increase in total heat production, as well as that of the components, was closely related to the difference in age and body weight at the first and second examination. The individual increment in heat production during growth was determined chiefly by postnatal age and weight gain. 4. Carbohydrate utilization was the dominant component of the total energy expended by the non-growing infants. During recovery, a further rise occurred in carbohydrate oxidation, while there was a moderate decrease in the participation of fat and protein.


Activity, energy metabolism and postnatal age relationship in low-birth-weight infants. The relationship between heat production and different activity levels was examined in 30 low-birth-weight (premature and small-for-gestational age) infants. A low level of spontaneous activity was preponderant, with a gradual shift from activity scores near zero to higher intensities with increasing postnatal age. There was a close correlation between activity and heat production. Older infants displayed a greater amount of spontaneous activity and a larger variation in heat production and activity-intensity relationship. The rise in heat production at a given activity intensity was greater in older than in younger infants indicating that the energy cost of identical activity increases with postnatal age. "Maximum" oxygen consumption increased with postnatal age.


Low dose irradiation in advanced tumours of head and neck. A material of 19 patients with T3 and T4 tumours of the mouth and pharynx was treated by fractionated low dose rate irradiation. Regression occurred in a large proportion of tumours but at the expense of a high rate of necrosis.


Epidermoid carcinoma of the tongue. Histologic grading in the clinical evaluation. In a series of 49 patients with epidermoic carcinoma of the tongue microscopy of the primary biopsy was performed, using a multifactorial grading system consisting of 8 parameters, each of 4 grades. The score value (degree of malignancy) revealed a statistically significant correlation with the frequency of regional metastases. As this was particularly marked in the T1 and T2 groups, it seems to be an important supplement to the clinical evaluation of risk groups.


Pre-operative short intensive radiation therapy of T3-T4 laryngeal carcinoma. A group of 33 patients with T3-T4 laryngeal carcinomas received in the period 1968 to 1972 pre-operative irradiation with 60Co followed by surgery. A total dose of 2 500 rad was given in 5 equal sesssions. The tumour free survival rates of these patients are compared to those of a comparable group of 57 patients receiving radiation therapy only. The overall results in the pre-operative group (64%) are superior to those in the group irradiated only. In glottic tumours the results were similar in both groups, but significantly superior in supraglottic tumours receiving pre-operative radiation therapy. The treatment schedule proposed is well-tolerated and surgery is usually performed before the onset of reaction.


Evaluation of time-dose factors in glottic tumors. Sixty patients with localized squamous cell carcinoma of the vocal cord without nodal or metastatic disease were treated with four fractions per week. No serious complications occurred with the dose and fractionation schedule as outlined. Voice quality after treatment has been satisfactory. After a minimum of two years follow-up the control rates for T1 and T2 tumors are 80% and 81.5%, respectively. All radiation therapy failures were cured surgically. A dose-response curve was constructed for T1 lesions, utilizing the Ellis' formula to derive the NSD, from data from different therapy centers. There appears to be no differences in the parameters studied between four and five fractions per week treatment schedules. A ret dose of approximately 1800 appears somewhat low for optimal control rates in T1 and T2 tumors.


Electron depth absorbed doses for small phantom depths. Comparison between different accelerators. Depth dose distributions at small phantom depths in polystyrene were measured with a liquid ionization chamber at six different accelerators. The absorbed dose at 0.5 mm depth relative to the absorbed dose maximum in the central beam varied between 0.77 and 0.92 for 10 MeV electrons. Generally the surface absorbed dose increased with increasing energy or decreasing field size. Results from measurements off axis indicate small differences from the data available for the central beam.


Treatment of disseminated carcinoma of the breast by metenolone enanthate. Forty-three patients with disseminated or inoperable carcinoma of the breast were treated with Metenolone Enanthate (Primobolan Depot) with doses of 400 to 1 200 mg/week for at least 3 months. Objective remissions lasting longer than 3 months occurred in 8 out of 41 evaluable patients. Soft tissue metastases responsed best. Liver and brain metastases were unaffected. The therapeutic efficiency of Primobolan Depot is comparable to that of testosterone propionate but the agent is less virilising.


Thyroid hormones and lymphoid cells.

Thyroid hormones and lymphoid cells. The impact of D- and L-forms of triiodothyronine and thyroxine on DNA-synthesis of human lymphoid cells was tested in vitro. The incorporation of 14C-thymidine into DNA was increased by addition of large quantities of both types of hormone in either racemic form.


Protection of the skin of mice against irradiation with cyclotron-accelerated helium ions by 2-mercaptoethylamine. Mouse skin was exposed to doses of 1 250 to 3 000 rad using a helium ion beam with modal LET of 15 keV per micron. The skin reactions were evaluated for mice treated with a topical application of 10% MEA in a cream base or a placebo 15 minutes before irradiation. A comparison of the skin reactions indicated that the MEA treatment resulted in a DMF of at least 1.2. The implication for radiation therapy was discussed.


99Tcm-solcocitran in the detection of bone malignancy. A new 99Tcm-labelled compound, 99Tcm-Solcocitran, has been introduced for detection of bone and brain malignancy. It is claimed to be specific for neoplastic tissue. In the present material, however, 99Tcm-Solcocitran was less sensitive in indicating metastatic bone lesions in patients than was 99Tcm-Diphosphonate or conventional radiography. Both 99Tcm compounds accumulated in fractures in dogs. 99Tcm-Solcocitran seems to offer no advantage over existing techniques in the detection of bone malignancy.


[Determination of the diffusion function of 25 MV x-rays in a tissue equivalent medium]. The diffusion function of 25 MV Roentgen rays in a tissue-equivalent material was determined experimentally as a function of the size of the beam and of the depth into the material. In order to characterize the beam, the attenuation of the beam in various materials was previously investigated. The results of the investigation demonstrate the important contribution of diffused radiation to the dose when using very high energy radiation.


Effect of low temperature on isolated mammalian heart. Effect of perfusion with low temperature Locki solution on the isolated hearts of adult rabbits and mongrel puppies was studied. The study showed no arrhythmias or myocardial fibrillation at low temperatures in the isolated mammalian heart.


Evaluation of tricuspid valvuloplasty with mitral valve replacement in severely ill patients. A group of twenty cases of class IV of New York Heart Association Classification is reported. They were selected among 55 cases of mitral valve replacement. Three patients died and this leaves us with a mortality rate of 15% which corresponds with that of others. Tricuspid valvuloplasty had to be carried out in seven cases. In two cases, reported in detail, two commissures and ring had to be repaired. The nature of pathology was organic and functional while in the remaining five cases it was only functional. None of the cases required tricuspid valve replacement. We believe that tricuspid valvuloplasty has an important position in heart surgery and should not be underestimated. Also, we conclude that no patient should be denied operation on the basis of the severity of his disease unless advanced coronary disease or primary myocardiac disease are also involved.


Osteochondromatosis of the hip joint. Report of a cast. Osteochondrmatosis of the hip is a rare disease in which segments of synovial membrane become cartilaginous. These may calcify or ossify forming osteocartilaginous masses as loose bodies. It occurs most often in young or middle-aged adults and the etiology of the condition is unknown. The diagnosis can be apparent with due consideration on clinical history and proper X-ray examination of the joint. One case of such disease with typical X-ray findings is reported.


Serum enzyme activity of hydroxybutyric dehydrogenase (HBD) and heat inactivated lactate dehydrogenase (LD) after operations on intracranial aneurysms. The relation between clinical signs of parenchymatous cell damage after brain surgery and the serum activity of the LD-isoenzymes determined either as HBD or as heat inactivated LD, has been studied in 44 patients operated upon for intracranial aneurysms. Seven patients had a postoperative increase of the serum enzyme activity above the upper normal limit. All these showed neurological symptoms as compared to only 14% of those who had a postoperative enzyme level within normal limits. This speaks strongly in favour of a relation between the brain cell damage and the increase of the serum activity of the LD-isoenzyme. Since only 15% of the patients had a pathological enzyme level, it is further suggested that an uncomplicated operation for intracranial aneurysm should not cause an increase of the HBD or heat inactivated LD above the upper normal limit.


Creatine kinase and lactate dehydrogenase in the cerebrospinal fluid in patients with head injuries. The concentration of CK and LDH in the cerebrospinal fluid was determined in 290 patients with head injuries. The highest concentration of these enzymes appeared in patients with the most severe brain injury. CK correlated somewhat better than LDH with the severity of the head injury. In the group with moderate head injuries there was no significant difference statistically between patients with increased CK level and patients with normal CK level in the cerebrospinal fluid with regard to the duration of posttraumatic headache, dizziness or working disability.


[The nosological position and histogenic origin of the so-called cerebellar astrocytomas (author's transl)]. The unusual status of the cerebellar astrocytoma is based upon clinical and histological evidence. "Bergstrand Tumour" is proposed as a new name for it. A new concept of its origin is put forward, namely that it is derived from the "tanycytes" (Horstmann) of the periventricular structures.


Epidemiology of chronic subdural haematoma. During the seven year period 1967-1973 a total of 64 residents of the City of Helsinki were diangosed as having chronic subdural haematomas. Forty of the patients were diagnosed during life at the Departments of Neurology and Neurosurgery, University of Helsinki, and treated surgically. Twenty four were diagnosed at autopsy at the Department of Forensic Medicine, University of Helsinki, at which the autopsies in virtually all cases of subdural haematoma in Helsinki are performed. The total of 64 cases gives an incidence of 1.72/100,000/year in the average population, the incidence increasing steeply with advancing age up to 7.35/100,000/year in the age groups 70-79 years.


Control of diabetes insipidus by continuous monitoring of the electrical conductivity of the urine with a simple device. An apparatur is desribed for continuous monitoring of electrical conductivity of urine for the control of diabetes insipidus. It consists of a flow through measuring cell connected to the urinary catheter, and a simple conductivity meter. Experiences with this measuring device, and its advantages, are described and  discussed.


Intracranial ganglioneuromas in children. Two cases of tumours of the sellar and suprasellar region in children, manifested clinically by visual and endocrine disturbances, are reported. In both cases surgical removal of the intracranial tumour was performed. The histological diagnosis was central ganglioneuroma, an extremely rare tumour in children. Also worthy of note was the altogether exceptional location in these children of central ganglioneuromas in the sellar and suprasellar region.


[Spinal cord compression caused by spinal aneurysmal bone cyst (author's transl)]. Spinal aneurysmal bone cyst is sufficiently rare for the authors to report this case with rapid evolution and development of paraplegia. Total removal was achieved, and clinical recovery remained complete six months after operation. The pathogenic, clinical, radiological, histological and therapeutic aspects are briefly reviewed and discussed.


Total removal of a craniopharyngioma. Technical note. A technique is described for dealing with large solid calcified fragments of craniopharyngiomas whose size would ordinarily render such a lesion inoperable.


Multiple tuberculomas of the brain. Report of a case. A case of multiple tuberculomas of the brain in a pregnant patient is reported. The symptoms and signs suggested a lesion of the cerebellum which was found to be only congested and oedematous at craniotomy. The correct diagnosis was made at autopsy.


[Von Eulenburg's congenital paramyotonia and aptitude for military service. Cases taken from a family with 25 cases since 1789]. The authors present four cases of von Eulenberg's paramyotonia. From the family history it was possible to follow the condition through seven generations since 1780; it confirms the autosomal dominant nature of genetic transmission, with almost complete penetrance. From the clinical standpoint, the condition observed is particularly pure, occurring exclusively in the cold. At no time were paralyses or adynamia independent of the myotonic phenomena and of temperature variations observed. The laboratory investigations carried out, ionic and enzyme, showed no abnormalities. Electromyographic study showed the presence of numerous true myotonic out-bursts, variable in shape and in amplitude, independant of the myotonic phenomenon, and present in the absence of exposure to cold. The effects of the condition on aptitude for military service are examined and in this respects the author recalls that the history of myotonia is intimately bound up with medico-military problems.


[Arteriovenous fistulae of the dura mater. Clinical and radiological study of 13 cases]. The authors studied 13 new cases of fistulae of the dura mater. With reference to these 13 cases, and to the literature, they propose a classification according to the type of drainage of the fistula: direct, into a dura mater lake, into a cortical vein. This clasification enables a better clinical and radiological approach to these anomalies.


[Recrudescence of imported malaria (apropos of 30 recent cases)]. 30 cases of imported malaria were diagnosed in the Laboratoire Central de Parasitologie of the Pitié-Salpêtrière C.H.U. in less than five months. The circumstances of appearance and the conditions of the patients' stay, the difficulties of the clinical diagnosis of the primary invasion, the gravity of P. falciparum attacks and the therapeutic schedules are presented. The accent is placed on the deficiencies of correctly prescribed anti-malaria chemotherapy and on the importance of information and sensitization of travellers.


Unusual glioma of the optic nerve.

Unusual glioma of the optic nerve. A 3 1/2-year-old white girl presented with unilateral proptosis and an orbital tumor that was diagnosed histopathologically as an unusual form of glioma of the optic nerve. The optic foramen was not enlarged but the ultrasonogram indicated a definite retrobulbar mass.


The treatment of acute horseshoe retinal tears by transconjunctival cryopexy. During the past 6 years, 59 consecutive eyes with operculated retinal tears have been treated successfully by transconjunctival cryopexy. This type of treatment risks fewer complications than scleral buckling. Its success implies that vitreous traction upon the retina may be short lived in most eyes or that its intensity diminishes considerably after the development of a retinal tear.


Granuloma pyogenicum of the conjunctiva. Granuloma pyogenicum or telangiectatic granuloma is an unusual clinical lesion which may occur anywhere on the body, but on rare occasions presents with ocular manifestations. Its occurrence on the lids has been reported in several instances, but few cases of isolated conjunctival changes have been documented. The purpose of this paper is to present a previously unreported case of histologically proven bilateral granuloma pyogenicum of the conjunctiva and to alert other ophthalmologists as to its significance in the differential diagnosis of conjunctival masses.


Cataract surgery: review of 500 consecutive cases. We believe that most cataract extraction procedures may be good in competent hands, but that complicated techniques do not necessarily give the best results. With inexperienced residents, or the occasional surgeon, a safe, simple method needs to be used until the skill of the operating surgeon may warrant more advanced techniques. A simple cataract procedure consisting of local anesthesia, limbal-based conjunctival flap, 3 postplaced 7-0 mildly chromicized gut sutures, 2 peripheral iridotomies and tumbling extraction of the lens with capsule forceps (indirect acting) is described. The low incidence of complications of all types would seem to negate the current trend of complicating the procedure. Further reports will include large series of cataracts done by resident physicians rather than by the instructors to try to further justify this position.


Use of ophthalmic gelfilm in retinal surgery. This report describes our experience with absorbable gelfilm in retinal detachment and intraocular foreign body surgical cases. The material was used as an intrascleral implant in 100 trapdoor retinal procedures. In 10 other cases it was used as a meridional implant under a silicone buckle, and in 2 cases it was used as a vitreous tamponade over the site where an intraocular foreign body was removed. The gelatin was found to be an excellent adjunct in retinal surgery. The material was easy to work with and there were no complications of erosion, extrusion, or infection. The indications for use of this material, as well as the advantages and disadvantages, are discussed.


Surgical management of persistent diplopia in blowout fractures of the orbit. Persistent diplopia continues as a problem in a significant number of patients following the surgical management of a blowout fracture of the orbital floor even when repaired within 15 days of the traumatic incident. Inferior rectus and inferior oblique muscles which have been incarcerated in a blowout fracture for longer periods have a worse prognosis for adequate functioning postoperatively. There is some presumptive evidence to suggest a myogenic or neurogenic cause for such dysfunction. Experiments with posterior fractures clearly demonstrate that the nerve entering the inferior rectus can be damaged. Vertical diplopia which persists beyond 3 months following release of entrapped muscle tissue requires surgical correction depending upon the degree of vertical dissociation. Motility surgery was required in 18 of 20 patients with persistent diplopia. Multiple muscle combinations were frequently required to achieve success. The criterion for a successful result was elimination of vertical diplopia in the primary and reading position. The elimination of persistent diplopia in association with blowout fractures of the orbit is usually possible even in late treated cases when one uses specific criteria for success. Three cases were considered cured since there was no diplopia in any direction of gaze, while 17 cases developed single binocular vision in the primary and reading positions. In these latter patients, on extreme upward or downward gaze, diplopia could still be demonstrated in all patients, especially when the individuals were specifically requested to look for diplopia.


[Pharyngeal constrictors and deglutition (apropos of 4 cases]. The authors describe four cases of deglutition disorders, even resulting in aphagia in two cases, in which the constrictor muscles of the pharynx were quite clearly entirely responsible. Electromanometry made diagnosis possibe for these patients and it is the only method capable of distinguishing crico-pharyngeal achalasis from paralysis of the constrictor muscles. The authors draw attention to the fundamental importance of this method of investigation in the pathology of deglutition. The propellent role of the constrictors, emphasized by some authors, rather than the upthrust of the tongues seems to be the borne theory out by these cases. Despite surgical ablation as recommended by most authors, or the spontaneous pathological disappearance of the crico-pharyngeal, the condition of the patients described was not improved; therefore it would seem wise, if a decision is taken to operate, not to make any promises to the patients about improvement of function insofar as aphagia is due to paralysis of the constrictors. Diagnosis, it should be remembered, can only be made after electromanometric investigation which is an essential preliminary to any therapeutic decision.


[Routine endoscopy of the esophagus in buccal, pharyngeal and laryngeal cancers]. We practiced a systematic endoscopy of the upper part of the aero-digestive tract on 160 patients suffering from a cancer in the mouth, the pharynx and the upper part of the larynx. This unit, going from the mouth to the cardia does really exist: it has the same epithelial coating, the same function and is liable to suffer the same damages. It is the seat of many well-known cancerous localizations that always need to be searched for on principle when face to face with any cancer. The endoscopic examination so conceived allowed the authors to find a cancerous association on the very level of the upper sero-digestive tract among 14 per cent of the patients; 4 out of these 14 per cent having oesophageal damages impossible to detect clinically on one hand, and often radiologically on the other hand. Morever, 3 out of 7 of lesions were tiny: from 1 to 3 millimetres, extending the limits of the diagnosis of the cancer of the aesophagus and perhaps leaving better therapeutic possibilities.


[Comparative analysis of electrophsiologic audiometric methods (A-EEG and ECoG)]. The authors consider technical problems, problems of interpretation and significance of responses posed by electrophysiological audiometric methods (electro-encephalographic audiometry and electro-cochleography) from their personal experience involving several hundred investigations. They have attempted to assess the respective diagnostic importance of these two method while stressing the fact that they are, in fact, complementary.


[Ultrasonic echography for exploration of parotid tumors]. The authors describe results obtained with ultrasonic echotomography for differential diagnosis of parotid tumours. A picture of the neoplasms is obtained and its benign or malignant nature is ascertained by graded sensitivity investigation.


[Effect of some antibiotics and chemotherapeutic preparations on Leptospira in vitro]. It was shown in vitro with the method of successive serial dilutions that polymyxin M, thilan, streptomycin, neomycin, sodium levomycetin succinate, brilliant green, tripaphlavin, azidin, aminoacrichin, and novarsenol had the most pronounced bactericidal effect on Leptospira. Combination of the antibiotics or the chemotherapeutics apart from azidin and tripaphlavin did not increase the bactericidal effect as compared to their use alone. The clinical and collection strains of Leptospira had the same sensitivity to the substances tested. The above drugs should be tested on animals with leptospirosis.


[Comparison of the effect of trypsin and chymotrypsin on the pharmacokinetics of penicillins in the body of rats]. Trypsin and chemotrypsin administered intramuscularly to rats in doses of 2 and 10 mg/kg respectively prior to benzylpenicillin, ampicillin or oxacillin administered also intramuscularly were studied with respect to their effect on the pharmacokinetics of the antibiotics. The latter 2 antibiotics were additionally studied after their oral administration. It was found that trypsin and chemotrypsin had almost the same effect on the pharmacokinetics of the penicillins in the animals, when administered intramuscularly and the effect did not depend on the doses of trypsin and chemotrypsin (2 and 10 mg/kg). No significant differences in the effect of the enzymes on the pharmacokinetics of ampicillin and oxacillin administered orally was registered. Combination of prior injection of every of the enzymes followed by oral administration of the semisynthetic penicillins resulted in a more pronounced increase in the levels of the antibiotics in the blood serum and organs of the rats as compared to that after intramuscular administration of the antibiotics.


[Isolation of Mycoplasma from the urine of patients with chronic pyelonephritis]. Bacteriological analysis of urine of 150 patients with chronic pyelonephritis was performed. As a result mycoplasma was isolated from urine of 25 patients. Mycoplasma and Coli bacteria or Proteus were isolated simultaneously from urine of 10 patients. Biochemical properties and sensitivity to antibiotics of 9 isolates were studied. The data provided recommendation of the urine analysis for the presence of mycoplasma.


[Clinical morphological picture of the mucosa of the middle ear in experimental chronic otitis media in rabbits treated with combined antibiotic aerosol preparations]. An new method of treating chronic purulent middle otitis with combined aerosol drugs (oxycyclosol, polysol, levovinylsol, vinysol) was developed at the USSR Research Institute on Antibiotics and tested experimentally on 20 Shinshilla rabbits. A 0.3 ml volume of microbial suspensition: Staphylococcus (group I), Ps. aeruginosa (group II), Proteus vulgaris (group III) and mixed microbial flora (group IV) were administered into the cavities of the middle ear of the rabbits from both sides. The acute process was made chronic by using decreased daily food ration and repeated putting of the rabbit extremeties into cool water. After that the rabbits were subjected to treatment with the above drugs for a week. Damages in the drum cavity mucosa with dystrophy, necrosis and cell separation were observed in the control (not treated) animals. Analogous changes were found also in the auditory tube. Signs of necrosis followed by decomposition were detected in the bone tissue. Only some thickening of the mucosa and bone wall of the drum cavity in the ears and single lymphoid and plasmic cells were recorded in the rabbits subjected to the treatment with the aerosol drugs.


[Biosynthesis and the isolation of the new anthracyclin antibiotics, violamycins A, BI, BII and their aglycones]. The conditions of fermentation, isolation and some of the physico-chemical properties of the new anthracycline antibiotics, i. e. viomycin A, BI, BII and their aglycones, produced by a strain of Streptomyces violaceus IMET JA 6844 are described. Violamycin A is mainly a complex of aminoglycosides of epsilon- and dzeta-isorhodomycinone, beta-rhodomycinone and (alpha)2-rhodomycinone. The sugar component is rhodosamine. Violomycin BI is mainly a complex of trisaccharides of the same aglycones mentioned above. The sugar components are rhodosamine, 2-desoxy-L-fucose and rhodinose. Violomycin BII is mainly a rhodosaminyl-2-desoxy-L-fucosyl-derivative of epsilon- and dzeta-isorhodomycinone, beta- and epsilon-rhodomycinone and (alpha)2-rhodomycinone. Violamycin complexes A, BI, BII mainly consist of 6 aglycone components which are similar to the other members of anthracyline antibiotics but can be diferentiated from them by physico-chemical and biological properties. Epsilon- and dzeta-isorhodomycinone, epsilon- and (alpha)2-rhodomycinone and dzeta-rhodomycinone one of the 8 minor components contained in the mixture of the aglycones of the violomycin complex so far has been determined as constituents of an antibiotic.


[Polymorphism of a culture of Actinomyces chromogenes var. trienicus, the producer of chromotrienine]. Variation of Actinomyces chromogenes var. trienicus 141-18 MSU, an organism producing trienin was studied under laboratory conditions. Nine stable spontaneous variants were isolated from the population of the initial culture when grown on Gause medium No. 1. The variants varied in differentiation and biosynthetic capacity, including such characteristics as size and form of the colonies, ability for formation of the aerial mycelium and its colour, capacity for sporulation, form of the spore chains and antibiotic production property. In the secondary structures the spores formed only in 6 variants out of 9 isolates. The spore form and spore membrane surface were close in all sporogenic variants, while there were significant differences in the structure of the sporophores. The variants forming the aerial mycelium of the same colour as that of the initial culture did not differ from it also by the nature of the spore chains (spirals with 3--8 turns). The variants with lighter aerial mycelium than that of the initial population formed straight sporophores or spirals with a small number of the turns (1--3). The comparative study of the antimicrobial spectrum of the variants and the component composition of the synthesized antibiotic complex showed that the asporogenic variants and dwarf variant signifcantly differed with respect to their phenotypes from the other cultures and had no antagonistic action. One of the assporogenic variants had only insignificant activity. All the spore forming variants did not differ from the initial culture in the complex of the antibiotics synthesized.


[Effect of gamma-irradiation on some biological and physico-chemical properties of polyene antibiotics]. Deep effect of gamma-rays on polyenic antibiotics was studied. It was shown that gamma-radiation induced radiation-chemical oxidation of the substances. The chromatographic analysis showed that the levorin degradation products were identical to the polyenic products of the antibiotic oxidative destruction. As for mycoheptin and amphotericin B, destruction of their molecules to non-polyenic products was observed. It was found that toxicity of the levorin aromatic heptaen did not practically change after gamma-irradiation in high doses. The toxicity of mycoheptin and amphotericin B, non-aromatic heptaens increased after exposure to high doses of gamma-rays.


[Sensitivity of Yersinia enterocolitica to antibiotics]. Sensitivity of 33 foreign and 10 native strains of Y. enterocolitica to tetracycline, aminoglycosides, penicillins, levomycetin and polymyxin was studied. All the strains proved to be resistant to penicillin, oxacillin and ampicillin: they produced penicillinase. The level of resistance to penicillin did not always correlate with penicillin activity. The ability of the native strains to acquire R-factor in vitro from Coli bacteria was shown.


[Optical rotary dispersion of some heptaene antibiotics]. Experimental differences in the curves of the optic rotation dispersion (ORD) of cystrans-heptaenic antibiotics were found. The ORD curves of amphotericin B, mycoheptin, levorin components and isolevorin A2, components of criptomycin and candidin were registered. The curves of the ORD which were smooth had been prepared in dimethylsulphoxide in the spectral range at 450 to 600 nm. In the spectral range at 300 to 420 nm the ORD curves appeared to be anomal with a complex Kotton effect, they were prepared in methyl alcohol. The Kotton effect was probably due to asymmetry of the electron membranes of polyenic chromophore induced by the other part of the polyen molecule. This was evident from the fact that the curve of the Kotton effect was situated in the same spectral range as the absorption bond of the polyenic chromophore. The oscillating structure in the absorption spectrum and the curve of the complex Kotton effect were analogous.


[Spontaneous and induced variability in Actinomyces rubiginosohelvolus, a new producer of the antibiotic rubomycin]. Mutants possessing 3 times higher activity as compared to the initial culture were obtained as a result of selection of active variants of Act. rubiginosonelvolus, a new organism producing rubomycin against the background of variation induced by N-methyl-N1-nitro-N-nitrozoguinidine, diethylsulphate and their combinations. Further selection among the mutants stable to 6-mercaptopurine and riboflavine resulted in obtaining an active culture No. 3912 at least 7 times more active with respect to rubomycin production than the initial soil culture.


[Effect of lyophilization methods on the formation of free radicals, the survivability and makeup of a population of the lincomycin producer]. It was shown that a short-time exposure of the spores of Act. roseolus 981 to air (oxygen) on their lyophilization by the chamber method resulted in formation of increased numbers of the free radicals in the lyophilized spores suspension and decreased the survival of the spores on their further storage under vacuum. The phenomena were less pronounced when the exposure of the spores to the air was excluded by using the collector method of lyophilization. This testified to the advantages of the latter method as compared to the chamber one. No effect of the lyophilization methods on the population composition of the spontaneous variants of Act. roseolus 981 was observed.


[Optimization of the nutrient medium makeup for the biosynthesis of carminomycin using mathematical methods of experimental design]. The nutrient medium for biosynthesis of carminomycin by Actinomadura carminata, strain 4281 was optimized with the methods of mathematical planning of the experiment. The starting variant of the medium, production of carminomycin on which was assumed equal to 100 per cent was enriched during the experiments carried out according to the patterns of the orthogonal latin squares. The production levels of carminomycin on the above medium was more than 3 times higher than those on the starting medium.


[New antibiotically active fluoroglucide from Pseudomonas aurantiaca]. A new metabolite with an antibiotic activity against grampositive bacteria in concentrations of 0.1--1.0 gamma/ml was isolated from the culture fluid of Pseudomonas aurantiaca. The study of its physico-chemical properties showed that it was di-2,4-diacetylfluoroglucylmethan. The conclusion was confirmed by synthetic studies. Di-2,4-diacetylfluoroglucylmethan belongs to the group of the antibiotics, derivatives of fluoroglucin, characteristics metabolites of Pseudomonas aurantiaca.


[Trichothecene inactivation by proteolytic enzymes from Trichothecium roseum Lk ex Fr]. Trichothecium roseum Lk ex Fr produces simultaneously trichothecin and proteolytic enzymes possessing fibrinolytic, thrombolytic and esterase activity. In addition to the function of splitting and consuming the substrate, the proteolytic enzymes of T. roseum are probably able to hydrolize the other bond in the molecule of trichothecin, which results in partial inactivation of the antibiotic in both the fungus culture and the model experiment on trichothecin contact with the preparations of the proteolytic enzymes. Presence of proteases of T. roseum may be considered as a protective mechanism for detoxication of the metabolites toxic for the organism.


[Mathematical model for the control and standardization of discs]. Analysis of tetracycline and erythromycin diagnostic discs manufactured in the USSR showed their conformity with the requirements of the USA Federal Register. Comparison of the antibiotic amounts extracting and diffusing from the discs showed that as an average 92 and 90 per cent of the extracted amounts of erythromycin and tetracycline respectively diffused into the agar. Subsequently, it is desirable that on control testing of the disc quality both the similarity of the antibiotic content in the discs and the real amount of the antibiotic diffusing into the agar should be considered. A statistically reliable correlation between the values of the growth inhibition zones around the discs with definite and constant amounts of erythromycin, tetracycline or oxacillin and different resistance levels for every staphylococcal strain was found. On the basis of such a control system it is possible to divide the staphyloccal strains into the groups with high, low and intermediate resistance levels to the above antibiotics. However, it is not possible to use such data for accurate calculation of the value of the minimum inhibitory concentration of unknown strains because of a high value of the main error.


[Joint action of nitrofuran preparations and bile acids on bacteria of the genus Proteus]. Sensitivity of 25 fresh isolates of Proteus to some nitrofuran drugs most widely used in the clinical practice, such as furacillin, furagin, furazolidone and nitrofurantoin was studied. When the drugs were used in combination with some bile acids, i.e. desoxycholic, dehydrocholic, cholic and glycocholic acids, significant in vitro potentiation of the antibacterial activity of the nitrofurans against the isolates was observed. The combinations of the drugs with desoxycholic acid proved to be most effective. In the presence of this acid the bacteriostatic dose of the drugs decreased several thousand times. Combination of the nitrofurans with the other acids resulted in an increase in the antimicrobial activity amounting to several hundred times. The combinations of the drugs with the bile acids had not only bacteriostatic but also bactericidal effect.


[New producer of carminomycin, Actinomycer cremeospinus sp. nov]. An actinomycete strain No. 85 was isolated from a soil sample on media with bleomycin. It was described as a representative of a new species. Actinomyces cremeospinus sp. nov. An antibiotic substance identical with carminomycin, an antitumor antibiotic was isolated from the culture fluid of the strain.


[Production of active mutants of a new species of rifamycin producer resistant to specific actinophage]. Selection of a phage-stable strain of a new species of the rifamycin-producing organism was carried out. The phage-stable mutants were selected with respect to the virulent phage 2739 isolated from a lysogenic culture of the rifamycin-producing organism. Spontaneous phage-stable mutants formed at a rate of 0.8 per cent. Most of them belonged to the morphological colony type with a decreased activity level. No shifts in variation with respect to the property of the antibiotic production were noted under the action of phage 2739. 62 per cent of the phage-stable variants isolated from the secondary growth colonies after infection with the phage were lysogenic and liberated phage 2739 to the culture fluid. Induction of mutations with MNNG, UV and gamma(Co30) rays increased the frequency of the phage-stable mutanta by 1.5 times. Active phage-resistant mutants stable to the phage because of its adsorption and liberating no phage 2739 into liquid media during its cultivation were selected.


[Polymorphism of a culture of the chromomycin producer, Actinomyces aburaviensis var. verrucosus]. Polymorphism of the chromomycin-producing orgnaism Act. aburaviensis var. verrucosus 144--3 was studied. The stable variants differed in the morphologo-cultural properties, assimilation of the carbon sources, the component composition of the luminescence substances and the quantitative property of the antibiotic production. A substance with violet luminescence was found in the culture of varient I in addition to chromomycin. Similarity of the phenotypes observed in variants 1 and 2 when grown on complex organic media is explained by intensive chromomycin production by variant 1 on such media. Active colonies may be selected according to the colour due to chromomycin. Forms with an activity almost 4 times higher than that of the initial culture were found among the colonies of variant 2.


[Isolation of new species of the genus Actinomadura on selective media with streptomycin and bruneomycin]. In the screening programme using selective media with streptomycin (25, 50 and 100 gamma/ml) and bruneomycin (0.5, 1 and 2 gamma/ml) 3 unusual actinomycetous cultures forming short, rarely long chains of straight, hook-like or spiral spores with 1 or rarely 2 turns were isolated. The study of the cell wall composition of the isolates showed that the walls contained meso-diaminopimelic acid and a sugar madurose. On the basis of the morphological structure and the cell wall composition the isolates were classified as belonging to Actinomadura. Comparison of the cultures with the Actinomadura species described in the literature showed that the isolates were new species of the genera, i. e. Am. coerulea sp. nov., Am. cremea sp. nov. and Am. salmonea sp. nov.


[Study of the effect of certain factors on the process of tetracycline antibiotic crystallization]. Since such factors as temperature and time of the process had a significant effect on the residual activity of the mother solution during crystallization of tetracyclines, it was necessary to study the effect of the above factors on the process for determination of the crystallization optimal conditions. The experimental data provided creation of the regression equations and the curves for similar levels of the main parameters for tetracycline and oxytetracycline were calculated. The lowest values of the mother solution activity within the ranges tested were observed at the temperature of 2 degrees and the time of 3 hours.


[Study of the antiviral action of gentamicin]. Experimental data on the effect of various concentrations of gentamycin on reproduction of VEE and Sindbis viruses in tissue culture are presented. It was found that gentamycin had no cytotoxic effect on the primary tripsinized chick embryon fibroblasts (CEF) when used in doses of 10, 20 or 30 mg/ml and only when used in a dose of 50 mg/ml it induced 50 percent destruction of the cell layer. Multiplication of the VEE and Sindbis viruses in the culture of CEF was inhibited in the presence of gentamycin by 1.5--3.5 lg PFU/ml. Two stages in the virus inhibiting effect of gentamycin were determined on the model of VEE, i. e. the stage of inhibition in the absence of visible damages of the cells and the stage associated with their destruction. The doses of gentamycin higher than 3 mg/ml inhibited in parallel the virus specific synthesis and synthesis of the cell proteins and nucleic acids. At the same time, when gentamycin was used in a dose of 10 mg/ml, no impairement of the cell viability was observed and the cell capacity to produce high titers of the model virus was reduced after incubation without the antibiotic for 24 hours. The antiviral activity of gentamycin were therefore determined by revers inhibition of the cell metabolic activity.


[Methods for detecting drug-resistant staphylococci in the human body under natural conditions]. Two methods were compared for determination of drug resistant staphylococci on the nasal mucosa of patients, i. e. the routine method for determination of staphylococcal sensitivity to antibiotics and the method of direct plating out of the starting material onto agarized media containing antibiotics. Staphylococci resistant to streptomycin, tetracycline, chloramphenicol, erythromycin, monomycin, axacillin and less frequent to penicillin were found more often with the 2nd method. A method of proportions was developed for testing sensitivity of staphylococci in purulent inflammatory foci of the patients. It provided characterization of the staphylococcal population from the foci by the number of the antibiotic resistant microbial cells.


[Action of antibiotic combinations with furacilin on the synthesis of proteins and nucleic acids in intact NAG-vibrio cells]. Furacillin in combination with such antibiotics as tetracycline, levomycetin or neomycin inhibited the synthesis of proteins in the cells of NAG-vibrios. Combination of 8 gamma/ml of furacillin and 0.125 gamma/ml of tetracycline inhibited the protein synthesis by 58.8 per cent, 8 gamma/ml of furacillin and 0.5 gamma/ml of levomycetin inhibited the synthesis by 61 per cent, 8 gamma/ml of furacillin and 4 gamma/ml of neomycin inhibited it by 59.5 per cent. At the same time furacillin alone in concentrations of 16 and 8 gamma/ml inhibited the protein synthesis by 69.1 and 37 per cent respectively, tetracycline alone in doses of 0.25 and 0.125 gamma/ml inhibited it by 51.3 and 34.7 per cent respectively, levomycetin alone in doses of 1 and 0.5 gamma/ml inhibited it by 54.4 and 33.2 per cent, enomycin in doses of 8 and 4 gamma/ml inhibited it by 54.4 and 22.6 per cent respectively. Therefore, when the above antibiotics were used in combination with furacillin the inhibitory effect of the drugs on the protein synthesis was summarized. When furacillin was combined with tetracycline or levomycetin in the above concentrations, the inhibitory effect on RNA synthesis (42 or 32 per cent respectively) was lower than that of furacillin alone (50.5 per cent). When furacillin was used in combination with neomycin, the inhibition of RNA synthesis increased up to 69 per cent. The increase in the inhibitory effect was also noted with respect to the synthesis of DNA. Combination of furacillin with tetracycline, levomycetin or neomhcin decreased the synthesis of DNA by 79.7, 85 or 85.8 per cent respectively as compared to the inhibitory effect of 8 gamma/ml of furacillin equal to 61 per cent.


[Efficient use of a combination of ampicillin and chymotrypsin]. The effect of chimotripsin on the level and duration of the ampicillin concentration increase in rats, as well as the effect of the enzyme on the in vitro antibiotic detection in the blood serum and organ homogenates of the animals was studied. It was found that rational combined use of ampicillin and chimotripsin required the enzyme administration not later than 1 hour before the antibiotic injection. Chimotripsin provided increased ampicillin levels in the blood serum and liver of the rats for at least 5 hours and in the kidneys and lungs for at least 4 hours. The enzyme present in the rats for 2 hours had no effect on determination of ampicillin activity in vitro in the presence of the blood serum and organ homogenates of the animals.


[Functional state of the adrenal cortex in experimental animals administered leyorin and its sodium salt perorally]. The effect of oral levorin and its sodium salt on the function of the adrenal cortex was studied experimentally on albino rats. The functional activity of the adrenal cortex was tested by the content of corticosterone in the peripheral blood determined fluorometrically. The results showed that levorin in a dose of 300 000 Unit/kg and its sodium salt in doses of 300 000 and 1 200 000 Units/kg used orally induced at definite periods of their administration a decrease in the corticosterone blood levels. At the same time a decrease in the weight coefficients of the thymus and prostate was observed.


[Study of the therapeutic effectiveness of oxacillin in treating the infectious forms of syphilis]. Data on efficiency of oxacillin therapy as applied to 45 patients with contagious forms of syphilis are presented. The drug was administered orally and intramuscularly to 40 and 5 patients respectively for 20 days. The periods of clearance from Trepanoma pallidum, disappearance of the external syphilis manifestations and the rate of the decrease in the titer of the serological reaction reagins are presented. The levels of oxacillin in the blood serum of 24 patients were determined for 5--6 hours from the moment of the treatment beginning. The study showed therapeutic efficiency of oxacillin.


[Acid-base properties and the thermodynamics of amphotericin B ionization in aqeous solutions]. Acid-base properties of amphotericin B, polyenic antibiotic in aqueous solutions was studied. A special procedure provided the use of potentiometric titration for investigation of ionization of the groups of the water-insoluble substance. The ionization constants of the carboxylic and amine groups of the antibiotic were determined at several temperatures. It was found that ionization of the acid group did not depend on the temperature. At the same time the heat effect of the amine group ionization was significant and amounted to about 10 kcal/mole. Thermodynamic analysis of the ionization process of amphotericin B in aqueous solutions was performed. Integral components defining the process energetics were calculated.


[Action of heliomycin on the incorporation of labelled protein precursors and nucleic acid in Staphylococcus aureus cells]. In concentrations of 0.05-0.10 gamma/ml geliomycin suppresses inclusion of C14-uracyl into the acid-soluble fractions of the staphylococcal cells. Inclusion of C14-leucine at the same concentrations of the antibiotics was suppressed to a lesser extent. The above concentrations of geliomycin had practically no effect on inclusion of C14-thimine. Suppression of C14-uracyl inclusion was observed in 5 minutes of the cell incubation with the antibiotic, a significant decrease in C14-leucine inclusion being observed only in 30 minutes of the incubation. The effect of geliomycin on the staphylococcal cells within the concentrations inhibiting the microbial growth and suppressing inclusion of labeled uracyl and leucine into the cells was of the bacteriostatic nature. It was supposed that the antibacterial effect of geliomycin was based on suppression of RNA synthesis.


[Changes in the mitotic regime of cultures of continuous human amniotic cells (line A1) subjected to the action of decamethoxin]. The effect of decamethoxin solutions on the cultures of the permanent line of the amniotic human cells (A1) was studied. In concentrations of 1000 and 50-500 gamma/ml decamethoxin induced fixation of the cell layer and destruction of cells A1 respectively. Higher dilutions of decamethoxin from 10 to 0.1 gamma/ml induced suppression of the mitotic activity and arrest of the cells in the telophase. Possible causes of the changes in the mitotic regimen are discussed. Therefore, decamethoxin slackened the cell dividing process in vitro and blocked passage of the cells from the telophase into period G1 of the interphase.


[Biological and physicochemical properties of the alpha- and beta-forms of cephaloridine]. Alfa- and delta forms of cephalosporin were compared. Biological activity, lantimicrobial spectrum and innocuousness of the forms and their physico-chemical properties were investigated with the methods of infrared and ultraviolet spectrophotometry and derivatography. No significant differences in the biological properties of alfa- and delta forms of cephalosporin were found. However, the ingrared spectrum of the delta-form was indicative of higher stability of its molecule, which was confirmed by higher thermostability of delta-cephalosporin.


[Gentamicin stability and a method for its quantititive determination]. Stability of gentamycin in solutions at various pH levels was studied. It was shown that in acid media inactivation proceeded according to the equation of the 1st order reaction. Dependence of the inactivation rate constant on the temperature corresponded to Arrenium equation. A polarimetric procedure for determination of gentamycin providing the assay of the antibiotic levels at various purification stages biginning from the eluates after the ion-exchange columns is described. The results obtained with the above procedure were shown to correlate satisfactorily with those of the microbiological analysis.


[Method of oblique illumination in studying the morphology of Staphylococcus aureus colonies sensitive and resistant to antibiotics]. The morphology of the colonies of Staph. aureus sensitive and resistant to antibiotics and the colonies with artificial resistance to benzylpenicillin, ampicillin, oxacillin, methicillin, cephaloridin and lincomycin was studied with the method of slanting light. Changes in the morphology of the colonies were most pronounced at the beginning of the microbial resistance development first of all in the cultures of Staph. aureus resistant to cephaloridin and lincomycin.


[Effect of penicillin on the intensity of formation of penicillin-resistant staphylococcal populations in the suppurative foci of patients]. The dynamics of sensitivity to penicillin of staphylococcal populations in purulent inflammatory foci of patients treated and not treated with antibiotics was estimated according to 4 indices. No reliable differences in the dynamics of sensitivity to penicillin were found in 2 groups of the patients, when estimation was performed with respect to the frequency of the penicillin resistant or penicillin sensitive staphylococci and detection of the penicillin resistant staphylococci by direct inoculation of the focal excretion to the medium with penicillin. A reliable increase in the percentage of the penicillin resistant staphylococci in the microbial population was observed only in the patients treated with penicillin.


[Microexudation phenomenon in the testing of antibiotics]. Changes in formation of the surface protein-polysaccharide layer (microexudate) on the cell surface under the action of inhibitor antibiotics, such as puromycin, actinomycin D and mitomycin C, as well as protein substances with adhesive action, such as horse serum and triprotamine in low doses were characterized quantitatively on a model of HeLa cells ellipsometrically. Under the action of puromycin, actinomycin D and mitomycin C formation of the microexudate ceased, which was in full accordance with the data on ceasation of the intracellular synthesis of protein, RNA and DNA under the action of the above antibiotics respectively. Inhibition of the microexudate formation was reversible. Still, the time of the inhibitory effect of puromycin and actinomycin D was longer than that of mitomycin C. Under the action of horse serum and triprotamine production of the microexudate by the cells was increased and accelerated. Accounting with the relative simplicity of the ellipsometric method and possibility of rapid estimation of the results, the data substantiate the expediency of using the phenomenon of microexudation as a cytopharmacological test.


[Change in the alkaline phosphatase activity and glycogen content in the leukocytes of white rat blood under the influence of penicillin preparations]. The contents of alkaline phosphatase and glycogen in the neutrophils of the peripheral blood of unbred albino rats weighing 170-200 gm were determined. Benzylpenicillin and oxacillin in doses of 50000 and 20000 Units/kg respectively were administered intramuscularly once a day over a long period of time. Two-phase changes in the contents of alkaline phosphatase and glycogen under the effect of penicillin were found. An increase in their contents was observed on the 5-10th days then it was followed by a decrease. Increase in the contents of the metabolites proceeded simultaneously with enhancing of the digestive capacity of the leucocytes and activity of lysozyme in them.


[Effect of streptomycin on the hearing function]. One of the main problems of the modern medicines within the last 10-15 years has been so-called drug disease. Toxic effect of the aminoglucoside antibiotics and streptomycin on the vestibular and auditory analysers is one of frequent and severe complications of their use. According to the author's observations treatment of 200 patients with streptomycin resulted in affection of their hearing in 40 to 80 cases. The ototoxicity was confirmed by audiograms, while the level of clinical signs and subjective complains did not always coincided with the audiograms. Audiometry should be performed at the beginning of the treatment and before the repeated courses of streptomycin therapy, and later it should be repeated during the treatment course every 10-15 days. Under the experimental conditions low doses of streptomycin used at early stages induced fine damages in the sensor cells of the cochlea which could be detected only histochemically.


[Actinomyces fulvoviolaceus ver. achromogenes var. nov., a producer of the new heptaene complex, fulvomycin]. An actinomycetous culture designated as LIA-0721 was isolated from a soil sample. It was close to Act. fulvoviolaceus by its morphologo-cultural features and differed from it in production of melanoid pigments and the spectrum of carbohydrate assimilation. This justified its classification as Act. fulvoviolaceus var. achromogenes var. nov. The culture produced new aromatic heptaens, i. e. fulvomycins A, B and C. Their physico- chemical and biological characteristics are presented.


[Effect of the degree of dilution of the antibiotic fermentation broths on the filtration indices]. Dilution of the fermentation broths with water before the mycelium separation lowered the specific cake resistance. The effect of the dilution on the filtration duration was different and depended on the fermentation broth type. As for the erythromycin fermentation broth, the time of its filtration decreased after the dilution, while the filtration time of the fermentation broths of the other 2 antibiotic-producing organisms increased after the dilution.


[Effect of thiamine, riboflavin and ascorbic acid on tetracycline, erythromycin and levomycetin activity]. The effect of antibiotics was estimated by inhibition of the protein increase in the broth culture of Staph, aureus during incubation at a temperature of 37 degrees for 18 hours. In some experiments preincubation of the antibiotic solutions with the vitamins for 2 hours at light and in dark was used. The antibiotic concentrations in gamma per 1 ml were equal to those of the vitamins. In the experiments with tetracycline and 2-hour preincubation at light the antibiotic in a concentration of 0.1gamma ml inhibited for certain the protein increase by 58.9%, in combination with thiamin it inhibited the protein by 60 per cent and in combination with ascorbic acid by 59%. Riboflavin lowered the activity of tetracycline to a value not differing for certain from the control one. In the experiments with preincubation in dark tetracycline inhibited the protein increase by 55.2%, in combination with thiamin it inhibited the protein increase by 50.5%, in combination with riboflavin by 53% and in combination with ascorbic acid by 57.2%. Erythromycin in a concentration of 0.03gamma/ml when preincubated at light inhibited the protein increase by 48.8% and in combinations with thiamin, riboflavin or ascorbic acid by 23, 27, 47.2% respectively. When preincubated in the darkness erythromycin alone inhibited the protein increase by 47.8% and in combinations with thiamin, riboflavin or ascorbic acid by 32.5, 51.1 or 49.8% respectively. The above vitamins has no effect on levomycetin activity.


[Study of the sensitivity of Halprowia (microorganisms of the OLT group) isolated in joint pathology to antibiotics and sodium sulfapyridazine in in ovo experiments]. Sensitivity to antibiotics and sodium sulfapiridasin of the microorganisms of group OLT, i. e. Halprowia and Chlamidia isolated from the joint fluid and synovial of the affected joints in patients with rheumatoid or non-specific infectious arthritis and Raiter syndrome was studied in ovo. The data provided determination of the spectrum of their sensitivity to various drugs. The antibiotics of the tetracycline group, i. e. olemorphocycline, tetracycline and rondomycin were shown to have the highest inhibitory effect. Penicillin and ampicillin only delayed the death of the infected embryons. As for kanamycin and streptomycin used in the doses tested, the agents were not sensitive to them. The isolates were also resistant to sodium sulfapiridasin which once more confirmed the questionable value of this criterion for differentiation of Halprowia.


[Dicloxacillin: its chemotherapeutic action and experimental kinetic characteristics]. Activity against 50 clinical staphylococcal strains, chemotherapeutic efficiency, absorption and distribution of dicloxacillin in animals were studied in comparison with oxacillin. It was found that dicloxacillin was superior to oxacillin with respect to a number of their properties. The antibiotic was characterized by a higher antistaphylococcal activity, especially with respect to methicillin resistant strains. It was more effective in treatment of staphylococcal pneumonia and septicopiemia of albino mice. The drug was better absorpted when used orally and was detected in the blood in therapeutic concentrations for long periods of time. The antibacterial titer of the blood serum after dicloxacillin administration was 4 times higher than that of oxacillin.


[Comparative study of the circulation of semisynthetic cephalosporins in the blood of rabbits]. Circulation of 4 semisynthetic cephalosporins, such as cephaloridin, cephalotin, cephradin and cephacetryl in the blood of rabbits after their intramuscular administration in single doses of 5 or 20 mg/kg was studied. The above antibiotics were satisfactorily absorbed into the blood reaching the maximum level within 15 to 30 minutes. The blood levels of cephalotin were the lowest and the rate of its elimination from the blood was higher than that of the other drugs. A four-fold increase in the doses of cephalosporins was not accompanied by a proportional increase in their levels in the rabbit blood, the time of the antibiotic circulation in the blood being not significantly changed.


[Study of the action of nystatin on the plasmatic membranes of the liver of rabbits]. The effect of mystatin on the plasmic membranes of the rabbit liver after intravenous administration of the antibiotic to the animals in a dose of 5 mg/kg was studied. It was found that intravenous administration of nystatin had no effect on the quantitative content of protein, lipids and nucleic acids in the plasmic membranes of the liver. The method of electrophoresis in polyacrylamide gel revealed significant changes in the composition of the liver membrane protein due to the treatment with nystatin. The effect of nystatin on the composition of lipids and fatty acids contained in the membrane lipids was also investigated. The data of the thin layer chromatography showed that nystatin did not affect the qualitative composition and the content of separate lipid fractions in the lipids of the liver plasmic membranes. However, the fatty acid analysis of the membrane lipids after intravenous administration of nystatin revealed a number of qualitative and quantitative differences in the composition of the lipid fatty acids of the membranes tested. The results showed that nystatin affected the membrane structures of the rabbit liver cells.


[Blood insulin levels during oral glucose tolerance tests in the obese child. Influence of age, sex, degree and duration of obesity]. A significant increase in basic and post-stimulation insulin secretion was observed in 173 obese children undergoing oral glucose tolerance tests. The hyperinsulinism, which was not related to hyperclycemia, was more important in older and heavier children. It was also observed however in younger children since the onset of obesity. It may therefore play a role in the maintenance of the obesity but also in its development. Various hypothesis to explain the origin of this hyperinsulinism and the adaptation of the system to it are discussed.


[A form of late propionic acidemia].

[A form of late propionic acidemia]. Report of 3 cases of propionic acidemia which concern one boy (O.M.) in whom a formed diagnosis of hyperglycemia with ketosis had been established, and two sisters (C.V. and K.V.) of another family. The activities of propionyl-CoA carboxylase in O.M. and C.V. fibroblasts were reduced to 4.5 and 2.5% of control. After two severe metabolic crisis, at 6 and 44 months of age, O.M. has at the present time (11yrs) a normal psychical development, and very few neurological disorders. Propionic acidemia was manifested only at 34 months of age in C.V. with a very severe crisis of acidoketosis with hypoglycemia, leading to neurological sequellae which are still important at 56 months of age. The disease was entirely latent in K.V. at 26 months, when the diagnosis was proven; it remains latent at 40 months. These case reports represent a special form of propionic acidemia with late clinical expression. Biological evolution does not seem to be affected by prolonged administration of biotine.


[Association of Fanconi's disease and hepatic tumor in a patient undergoing long-term androgen treatment]. A Fanconi's disease was discovered in a 9 1/2 year old girl. She received androgens daily and died with a severe aplastic attack after 4 years of evolution. Hepatic involvement of treatment with androgens was regularly checked. Autopsy however, showed a multinodular adenoma of the liver without any malignant manifestation. Relationships between aplastic anemia, long-term treatment with androgens and tumour of the liver are discussed. The difficulty of in vivo diagnosis is emphasized.


[Experimental results with new radiopharmaceuticals in autochthon brain tumors of rats (author's transl)]. It could be demonstrated by own investigations that ENU-tumors (brain-tumors induced with Ethyl-Nitroso-Urea) are better for clinical questions than the usual transplantation tumors. In this experimental study the temporal and quantitative condition of accumulation of 64Cu-Dimethylglyoxim and 59Fe-Acetyl-Acetone was investigated in rats with ENU-tumors compared with 99mTc-Pertnetate and and 67Ga-Citrate to answer the questions wether 64Cu-Dimethylglyoxim and 59Fe-Acetyl-Acetone are qualified for brain scanning. 64Cu-Dimethylglyoxim and 59Fe-Acetyl-Acetone show like 99mTc-Pertechnetate and 67Ga-Citrate certain affinity to the tumor. At the same time they accumulate in healthy tissues, too. The kinetice of the single radiopharmaceuticals is different. The rates of accumulation of 64Cu-Dimethylglyoxim after 24 hours and of 59Fe-Acetyl Acetone after 4 hours correspond to the rates of accumulation of 99mTc-Pertechnetate after 1 hour. Opposite to this rates of accumulation of 67Ga-Citrate are, because of the high accumulation in the bone, distinctly worse. There are 3 consequences: 1. Brain scintigraphical investigations should not be made with 67Ga-Citrate. 2. Brain scans with 64Cu-Dimethylglyoxim and 59Fe-Acetyl-Acetone will give no better results than scans with 99mTc-Pertechnetate. 3. Further investigations with 64Cu-Dimethylglyoxim and 59Fe-Acetyl-Acetone are not indicated.


[On the mode of action of heterologous antileukemic sera. Growth of syngeneically transplanted leukemia cells on serum treated neonatally thymectomized mice (author's transl)]. A heterologous antiserum against a Nitrosomethylurea--induced mouse leukemia prevented the outgrowth of syngeneically transplanted leukemia cells in neonatally thymectomized mice. After subcutaneous challenge with 50 000 leukemia-ascites cells thymectomized CBA mice at the age of 8 weeks were given 5 intraperitoneal injections each of 0,1 ml of the heterologous serum. While the antileukemic serum protected 9 out of 11 mice all of the 11 mice treated with normal rabbit serum developed a tumor. The absence of the thymus was confirmed by macroscopic control and by the absence of antibodies against the injected rabbit serum. With regard to previous findings showing a cooperation of heterologous antibodies with host cells as responsible for the antileukemic effect this result indicates that the effector cells are thymus-independent.


[Relationship between patient delay and prognosis in gastric cancer in an unselected population (author's transl)]. Whereas the morphology of malignant neoplastia is well known, exact information on the natural history of cancer is lacking. Some hints in this direction can be gained from detailed observations of the course of disease and from correlations between duration of history and prognosis. In the literature, views on the dependence of prognosis on duration of delay are conflicting. This was the reason why we examined this relationship in gastric cancer in the region of Erfurt, GDR, based on the unselected data of the cancer registry. 1838 cases of gastric cancer in male in 1960--1969 could be evaluated concerning prognosis and patient delay. In 2575 cases, relationship between duration of delay and clinical stage as well as mode of treatment could be investigated. From the statistical evaluation it was concluded that a long history is a sign of a less aggressive tumour growth. A short delay seems to be an index of adverse host-tumour relations. Better treatment results can be expected by shortening of patient delay. Possibilities to change the situation are discussed. A more centralized organisation of surgical care is proposed.


[Problems in the diagnostic of primary gastric stump cancer and recurrences of gastric cancer. A comparison of X-ray diagnostic and endoscopy (author's transl)]. X-ray findings and gastroscopic findings of patients with primary gastric stump cancer and recurrences of gastric cancer are compared. These findings are compared with the observations of operations. The reasons of false diagnoses and doubtful tentative diagnoses were analyzed. In the analysis of X-ray pictures especially the benign operative caused and the postoperative alterations of the wall and mucosa of the stomach must delimit from infiltrative and polypous increasing tumors. The postoperative control examination may be valuable for the diagnosis, because it gives the possibilities for comparison. Roentgenography in double contrast relieves the diagnosis. Stenosing processes of the cardia and anastomose causes difficulties in differential diagnosis in gastroscopy opposite to scared alterations. The aimed biopsy improves the tumor protection. Both examination techniques shows difficulties in recognition of recurrences, which develop from the duodenal stump. Only a special examination technique leads to an improvement of the results. The instruction and experience of the examiner, the knowledge of tumor diagnostics and of the methods of operations and of the postoperative alterations are for the diagnosis of these processes of decisive importance. X-ray examination and endoscopy are two supplementing examination methods.


[The present state of chemotherapy of gastric cancer (author's transl)]. The therapeutic results in stomach cancer are still very poor. Especially in advanced stages of the disease, cytostatic treatment is of little value. The most promising drugs available at present are 5-fluoroaracil or its analogues, Mitomycin C, and Chromomycin A3. Proper combinations of cytostatics are expected to become more therapeutic tools. Further chances of improving therapeutic results are seen in the combination of surgery with irradiation and chemotherapy. Such efforts should include individualization of the therapy with regard to factors of the tumor-host relationships influencing the prognosis, and utilization of tumor-biological data.


[Patho-anatomical characteristics of renal cell cancer]. A total of 61 observations on nephrocellular cancer were carried out. It was established that the tumour was not uniform by its histological structure neither in the primary node nor in metastases. Four variants of a histological structure of the cancer were identified: clear-cell, granular, sarcoma-like, and grandular. The one-type histological structure (one variant) in the primary node and in the most common metastases was identified nearly with the same frequency--in 60-66% of the cases. In the rest of the cases the tumour was of a mixed structure; more often there were observed combinations of 2 variants and more seldom--of 3 or 4 combinations. As a rule, metastases histologically corresponded to the primary node, but had peculiar features of their own depending on their localization. Divercity of morphological structures of tumours should be born in mind in making the histological diagnosis of nephrocellular cancer, partitularly if the volume of tissues obtained is small.


[Dynamics of morphological changes in the spleen in lymphogranulomatosis in children (according to the results of the study of surgical material)]. Results of pathomorphological studies of the spleens removed during the operation in 17 children with lymphogranulomatosis are discussed. An attempt is made to follow up stages of initiating and development of a pathological process in the spleen. A classification of specific changes in the spleen with singling out of established morphological variants is presented. It was found out that a lymphogranulomatous process in the cervical lymph nodes "outstripped" the development of specific changes in the spleen.


[Transformation in the lymphatic system of the heart and myocardium in congestion with lymph]. Changes in the heart in regional songestion of the lymph were studied both on sectional (26 observations) and experimental (20 dogs) material. It was shown that blocking of the lymphatic ways brought about dilatation and deformation of lymphatic capillaries and vessels, growth of capillaries, formation of lymphatic lacunas, varicosis of the wall of lymphatic vessels, and -- in complete obstruction of the lymph flow -- the appearance of lympho-venous shunts. In the myocardium stroma there were observed oedema, lympho-histiocytic and plasmocellular infiltrations, and in muscle cells -- dystrophic and necrobiotic changes. The degree of manifestation of the disorders depended upon the duration of congestion of the lymph; their outcome is replacing and stromogenous cardiosclerosis.


[State of the mucus membrane of the small intestine in upper intestinal fistulas]. In modeled experiments of 23 polyfistulous dogs with a reproduced high complete small-intestine fistula it was established that enteral compensation of water-electrolyte losses by means of a saline solution, isotonic and isoionic to the chyme, contributed to the maintenance of the water-salt balance for a prolonged period of time, kept up the animals' life and ensured the return to normalcy following the closure of the fistula. Preservation of the function of absorption by the small intestine was confirmed by the data of morphological investigations of 403 bioptic specimens of the mucosa from various parts of the small intestine repitedly taken in the course of the experiments. The data obtained testify to the absence of atrophy of villi and nakedness of their stroma, despite the intravital detachment of the epithelium into the lumen of the intestine, as well as to hyperproduction of the mucus, dilatation of the vessels of the circulatory and lymphatic systems, to retention of the mitotic activity.


[Ultrastructure of the neuromuscular junction in myasthenia]. The ultrastructure of neuromuscular synapses were investigated in bioptic specimens of muscles in 15 patients with myasthenia. Changes were detected in the pre- and postsynaptic structures. As a rule, the process initiates with appearance of destructive changes in the terminals of axones and in the adjacent to them areas of the "sole" of the neuromuscular junction, which may lead to destruction of synaptic contacts. In some part of synapses, together with destructive changes, there were observed also regenerative changes. The most representative group of synapses were those possessing the following characteristics of the ultrastructure: an increased electron density of the axoplasm and a greater number of mitochondria in the terminals of the axones; changes in the organization of the symaptic cleft and folds; impoverishment of the "sole" in organellas; all these signs, according to the literature reports, should be considered as typical of myasthenic lesions of the neuromuscular synapses. Collation of the changes observed with the duration periods of the disease, as well as the fact that these changes can be seen in the same patients, justify the assumption about the existence of different stages of the synaptic defect: destructive, destructive-regenerative and myasthenic. From this point of view, the appearance of "myasthenic" synapses may be considered as a result of the proceding destructive-regenerative process.


[Influence of iodine preparations and triiodothyronine on the histological structure of the thyroid gland in experimental goiter]. Histological changes in the thyroid gland of rats in experimental goiter caused by administration of 6-methylthiouracil during 9 months, as well as changes in the structure of these glands under the effect of diurnal ingestion with food of microiodine (iodized potassium 2 mg+iodine 0.2 mg per animal), diiodotyrosine (1.25 mg per animal) and triiodthyronine (5 mcg per animal) are described. As a result of the exposure to the above mentioned preparations, there were noted a decrease in the weight of the thyroid glands reduction in the number and size of microadenoms therein, a drop of the intensity of hyperplastic processes in the thyroid epithelium, and an increased proliferation of clear cells. The greatest effect was observed in the animals which received triiodothyronine: weight and histological structure of the glands in these animals was approximating the norm. There were revealed anaplastic changes in the microadenomas remained after the exposure to iodine preparations and triiodothyronine, and an increased proliferation of clear cells with formation of microadenoms out of them.


[Chronic gastric ulcer penetrating into the heart]. A case of penetration of chronic gastric ulcer into the thickness of the posterior wall of the heart in a 65-year-old female patient is described. Rupture of the wall at the site of penetration caused hemorrhage into the gastric cavity and the patient died due to loss of blood.


[Histological properties of the endothelium of major vessels]. The article deals with histological properties of the endothelium of the major vessels in mammals and in man. Biological features of this tissue and analysis of its organization are discussed. The material presented justifies consideration of the endothelial lining of the major vessels and veins as a specialized tissue of the vascular system which retains its capacity of capillaroformation. Its epitheliomorphic character and belonging to the angiodermal type of tissues are beyond doubt.


[Vessels of the microcirculatory bed of the heart in myocardial infarction]. Vessels of the microcirculatory bed of the heart in myocardial infarction were studied on the basis of the material of 21 section observations using histological, histochemical methods and the technique of impregnation of films of the epicardium developed by V. V. Kupriyanov. In the ischemic stage in the zone of ischemia and in perifocal areas there were noted signs of increased vascular permeability and impairment of hemodynamics: plethora of the venous department of the microcirculatory system, stasis of the blood in capillaries, spasm and paresis of vessels of the microcirculation. In the necrotic stage in the zone of necrosis there were observed destruction of vessels of the microcirculatory bed; in the peri-infarction zone--drastic plethora of veins, venules and capillaries, higher vascular permeability, leucostasis, leucopedesis, perivascular cellular infiltrates, destruction of vessels of the microcirculatory bed, dilatation of lymphatic vessels; in the intact zone--venous plethora and elevated permeability. In cases of shocks and collapses in vessels of the microcirculatory bed of the heart beyond the zone of necrosis aggregations of erythrocytes were found. In the reparative stage newly formed vessels in the granulation tissue were observed; In the post-infarction scars sinusoid vascular cavities and arteries of the closing type were noted.


[Pathomorphology of the vascular bed of the lungs and pleura in the presence of hypervolemia of the pulmonary circulation]. Blood and lymphatic vessels of the lungs and the pleura in 23 infants aged below one year, who had died of congenital cardiac defects with hypervolemia of the lesser circulation (coarctation of the aorta, transposition of the major vessels, general arterial trunk in combination with septal defects, open arterial canal and other anomalies) and in 5 dogs with artificial anastomosis of Blalock (3), Cooley (I) and Pootts (I) were studied; In treatment of the materials various histological and histochemical methods, micropreparation and impregnation of total preparation according to Ranvier's and V. V; Kupriyanov's techniques were used. The results obtained showed that an excessive blood content of the lesser circulation was accompanied by onset in the vessels of the lungs and the pleura of various accomodative changes, which were particularly pronounced in the system of microcirculation. It was established that functional insufficiency of the adaptive mechanisms led to the "breakdown" of compensation, impairment of blood and lymph circulation in the terminal vascular bed of the lungs and to grave secondary alterations in the organ. It was shown that early correction of hypervolemia of the lesser circulation in the experiment brought about normalization of hemodynamics in the lungs and more or less full recovery of the structure of microvessels of the regional bed.


[Morphogenesis of experimental primary pulmonary coccidioidal mycosis]. Morphogenesis of experimental primary pulmonary coccidioidomycosis in white mice was studied. The aspirated particles of the mycelium by the 5th day formed sporilating sporangiums, the latter being the main cause of a specific inflammatory process. Three stages in the development of the infectious process were singled out: incubation, in the course of which accumulation of the pathogene in the lungs took place (the first seven days), initiation and progressing of pneumonia, culminated with the animals' perish in the course of 12-14 days.


[Melanosis of the large intestine].

[Melanosis of the large intestine]. Studies of 100 appendices and 20 snips of the large intestine in cancer (17) and in Hirschprung's disease (3) were carried out, which showed that enterochromaffin cells containing greyish-brown pigment in cytoplasm, constituted the permanent constituent of the epithelial linings of these organs. A possibility of phagocytosis of this pigment by macrophages of the connective layer of the mucous membrane is described. Basing on the analysis of literature data and her own findings the author comes to the conclusion that the phagocytoused enterochromaffin pigment in macrophages of the mucous membrane corresponds to the so-called melanin of the large intestine. This is evidenced from the similarity of histochemical reachions and the pattern of distribution of the said pigment and the enterochromaffin cells. An analogy with epiphysis is drawn, where as a side product of serotonin--melanin, a specific pigment, is also formed.


[Morphologic characteristics of the late results of sigmoid colpopoiesis]. Results of morphological investigations of an artificial vagina of the wall of the sigmoid flexure 29-44 pears after the plastics are presented. In two cases there were revealed atrophy of the mucous membrane, sclerosis of the submucous layer and non-uniform hypertrophy of muscular layers. In one patient signs of nonspecific ulcerative colitis which developed several years before the incision of the artificial vagina were noted. Changes observed in the large intestine following sigmoidal colpopoiesis indicate to the stability of structures of the organs transferred under unusual conditions of existence;


[Use of apparatus POOS-I for determination of the DNA concentration of lymphoid tissue]. Using the apparatus "POOS-I" (a device for measuring the reflecting power) the author carried out microspectrophotometric determination of the DNA content in the lymphoid tissue of mice following gamma-irradiation and transplantation of the syngenic and allogenic bone marrow. An amount of DNA was expressed as a relative value representing optical density of histological sections stained after Feulgenmthis method has proved to be a sensitive objective test for evaluation of the extent of lesion and restoration of the lymphoid tissuek0


[Orientation of the wall of the small intestine for electron microscope studies]. A simple and reliable technique for orientation of small pieces of the intestine is suggested; the technique makes it possible to investigate semi-thin sections under light microscope, and ultrastructural topography of the intestine wall--in electron microscope.


Retention of 45Ca in rats and lambs associated with the onset of nutritional muscular dystrophy. Nutritional myopathy has been induced in both rats and lambs by feeding diets low in selenium. The distribution of 45Ca, administered as 45CaCl2, has been examined firstly by autoradiography, and secondly by measuring the excretion of 45Ca in urine and faeces. Autoradiographs of skeletal muscle from unsupplemented animals showed radioactivity over discrete muscle fibres at a stage when no abnormalities were apparent using conventional staining techniques. Similar retention of 45Ca was found in some of the tubules in the kidneys of selenium-deficient rats. Total excretion in urine and faeces of lambs, examined for 48 h after intravenous administration of 45CaCl2, showed that in normal animals 18-6% of the dose was excreted, whereas in dystrophic lambs 12-0% was lost. The difference was significant at the 2% level. The respiratory rates of isolated skeletal muscle mitochondria, measured polarographically in the presence of glutamate and pyruvate as substrates, were low for dystrophic rats. Respiratory control indices were 1-0 for the same preparations but for supplemented rats they were all above 1-0. The differences in respiratory rates were significant at the 1% level. The major conclusion drawn from the results of these experiments is that one of the first effects of sleenium deficiency which can be visualized is the abnormal retention of calcium by individual muscle fibres.


Characterization of the RNA synthesizing activity of isolated kidney nuclei. The limiting factor in RNA synthesis by isolated kidney nuclei is RNA nucleotidyltransferase at high salt concentrations but at low salt concentrations template availability becomes limiting. alpha-Amanitin inhibits 85% of the activity at high salt concentrations but only 20-50% of the activity at low salt concentrations. Exogenous DNA is utilized at low salt concentrations [up to 0-1M (NH4)2SO4] but not at high salt concentrations. The effect of increasing salt concentration is mainly to cause an increase in the length of chains synthesized. Initiation rates are not increased by high salt concentrations. The apparent Km for UTP is 8-10 muM at high salt concentrations, indicating that assays performed at low UTP concentrations are likely to give inaccurate results. The activation energy for the reaction at low salt concentration is less than that for the reaction at high salt concentration. The RNA synthesizing capacity of kidney nuclei is dependent on the method of isolation, and preparation by a modification of the Chauveau method (Chauveau et al. 1956) yields the most active nuclei.


Responses to the lowering of magnesium and calcium concentrations in the cerebrospinal fluid of unanesthetized sheep. A technique for ventriculolumbar perfusion of the cerebrospinal fluid space has been used to study the neuromuscular effects of low concentrations of magnesium and calcium in the cerebrospinal fluid of conscious sheep. Perfusion with synthetic cerebrospinal fluid solutions containing less than 0-6 mg magnesium/100 ml produced episodes of tetany which were abolished by perfusion with a solution of normal magnesium concentration. This suggests that the low cerebrospinal fluid magnesium concentrations reported in cases of hypomagneseamic tetany may result in changes within the central nervous system that could produce the nervous signs. Perfusates with a calcium concentration below 2-0 mg/100 ml caused hyperpnoea and continuous muscle tremors. Magnesium (0-6 mg/100 ml) and calcium (2-0 mg/100 ml) perfused simultaneously acted synergistically to produce signs characteristic of low levels of each of the ions.


Effects of intravenous infusion of mimosine on wool growth of Merino sheep. Merino sheep were given continuous intravenous infusions of L-mimosine for periods of 1 1/2, 2 or 21 days; efficacy as a defleecing procedure and effects on subsequent wool growth were measured. In addition, the amino acids tyrosine, phenylalanine and cystine were investigates as antagonists to the effects of mimosine. Infusions for 1 1/2 or 2 days at the daily rate of 80-120 mg/kg caused a cessation of wool growth by 1 1/2-2 days from the start of infusion, and all sheep were subsequently defleeced. It was estimated that, on average, fibre growth stopped for 10 1/2-13 days in four sheep after a 2-day infusion, and for 5 1/2 and 9 1/2 days in two sheep after an infusion for 1 1/2 days. There was considerable variation in the time taken for new fibres to recommence growth. During the period 3-5 weeks after infusion of mimosine, length growth rate was consistently greater than the pretreatment rate. Likewise, fibre diameter was greater in three out of the four sheep. As a result, the volume growth rate of fibres was greater post-treatment than it was pretreatment. Infusion for 3 weeks at the daily rate of 21-24 mg/kg did not stop wool growth. However, both length growth rate and fibre diameter were considerably depressed, and after 12 days' infusion, fibre diameter and volume growth rate were reduced to less than half the pretreatment values, and wool fibres were very weak. After the mimosine infusion stopped, fibre diameter increased to above pretreatment values and remained ther for the period of 2-3 weeks studied. The concurrent infusion of tyrosine, phenylalanine or cystine with mimosine failed to prevent any of the effects of mimosine on wool growth.


Fate of mimosine administered orally to sheep and its effectiveness as a defleecing agent. Mimosine was administered orally to Merino sheep once daily for periods of 1-3 days, either as the isolated compound or in the foliage of Leucaena leucocephala. A single daily dose of mimosine of 450 or 600 mg/kg body weight was effective for defleecing sheep. A daily dose rate of 300 mg/kg was effective for defleecing sheep if given on two successive days. The effectiveness of a treatment for defleecing sheep was related to the concentration of mimosine in plasma following dosing; defleecing ensued when the concentration of mimosine in plasma was maintained above 0-1 mmol/l for at least 30 h. The main products excreted in urine were mimosine and 3,4-dihydroxypyridine (DHP); small amounts of mimosinamine were also excreted. During the first day following dosing, the major excretory product was mimosine; DHP was an important component during the second and third days. In the three days following the start of dosing, between 32 and 53% of the mimosine given was accounted for as mimosine in the urine. Following an intravenous infusion of mimosine, no DHP was detected in urine; most of the mimosine was excreted intact but a small amount (c. 9%) was excreted as mimosinamine.


Effects of insulin hypoglycaemia in the sheep on jugular haematocrit and plasma corticosteroid concentrations. Insulin hypoglycaemia, by acting as a stressor, caused an increase in plasma corticosteroid concentration in sheep. It did not increase jugular haematocrit in splenectomized sheep, but caused an increase, presumably by splenic contraction, in the following sheep: two control, one with one adrenal cortex as its only adrenal tissue, two with denervated spleens, and two splanchnicotomized animals. These preparations showed that insulin hypoglycaemia can cause a splenic contraction in the absence of an increase in plasma adrenaline and after splenic extrinsic denervation.


Renal response to intravenous phosphate infusion in the sheep. Renal clearance experiments were performed on six Merino ewes in which plasma phosphate concentrations were increased by the intravenous infusion of isohydric sodium phosphate. As the phosphate load to the kidney increased, the renal tubular reabsorptive capacity became saturated and a definite tubular maximum for phosphate reabsorption (Tmp) was demonstrated. The Tmp was directly related to the glomerular filtration rate and had a mean value of 333-1+/-27-0 (s.e.m.) mumol/min or 416-6+/-13-5 mumol/100 ml glomerular filtrate. Calcium infused concurrently with phosphate in order to maintain plasma total calcium levels did not alter the Tmp. Ultrafilterability of calcium and phosphate in the plasma decreased with phosphate infusion and this was accentuated by an accompanying calcium infusion. The Tmp in sheep's kidney is higher than in non-ruminant animals and the implications of this are discussed.