Qualitative and quantitative preservation of the fine structure of absorptive cells in cultured biopsies of human small-intestine. The fine structure of the absorptive cells in human small-intestinal biopsies cultured for 6, 24, and 48 h was analyzed qualitatively and quantitatively. The findings show generally good preservation of the cultured absorptive cells and a normal distribution, size, and relative volume of their cell organelles, but there was a systematic decrease in the apical cell surface and an increase in the number of apical vesicles and tubules after culturing. Since the apical vesicles and tubules are thought to have a function in the transport of cell-coat material from the Golgi apparatus to the cell surface, these findings raise the question of whether a delayed transport or extrusion of cell surface material occurs. The diminished relative volume of the mitochondria and the increased signs of autophagy in some poorly preserved absorptive cells, are assumed to be an adaption to less favourable culture conditions.


Changes within vascular bundles of rodent kidneys caused by different diets. Morphological effects caused by two different diets (low protein-high water intake, and high protein-restricted water) on the vascular bundles in the outer medullary zone of the kidney were studied in the laboratory white mouse and in the golden spiny mouse (Acomys russatus, Muridae). In both rodents, when on a low protein-high water intake diet, considerable interstitial substance was found between the vasa recta of the bundles. No interstitial substance was found in animals on high protein-low water intake diet; as a result the vasa recta of the vascular bundle adhered closely. The low protein-high water intake diet caused a marked diuresis, low urine osmolality and low urinary urea concentration. It is assumed that the increase in interstitial substance between the vasa recta of the vascular bundle lowers the efficiency of the counter current barrier system for urea in the kidney and, as a consequence, the medullary urea gradient and urine concentrating capacity decreases. In animals on a high protein diet, the closely juxtaposed vasa recta assure an efficient countercurrent exchange, leading to accumulation and maintenance of a large urea gradient in the medulla and maximal urine concentration. It is suggested that the amount of interstitial material between the vasa recta of the vascular bundle might serve as a modulating factor for the urea concentration in the kidney.


Studies on the surface coat of Paramecium aurelia. II. Relationship to the immobilization antigen. Correlations between the presence of surface coat and immobilization antigen of Paramecium tetraurelia were studied. Supravital, partial removal of the surface coat resulted in accelerated response of monobacterially and axenically grown cells to the homologous antiserum. Ciliates pretreated with trypsin or pronase (0.5 mg/ml for 45 min at 0-4 degrees C) were immobilized approximately twice as fast as untreated control cells. The probable localization of at least part, of the immobilization antigen within the surface coat of P. tetraurelia is discussed.


Induction of mixed function oxidases on oral administration of dieldrin. The administration of dieldrin (30 mg/kg body weight) caused an increase in the liver weight of rats. The metabolism of aflatoxins B1 and G1 by the microsomes obtained from the liver of dieldrin-treated animals was enhanced significantly as compared to the controls showing that dieldrin increased the activity of mixed function hydroxylases. Dieldrin caused an increase in the activity of liver microsomal NADPH oxidase and a decrease in the lipid peroxidation. Dieldrin brought about an increase in the phosphatidylcholine content of rat liver.


Heavy metal complexation in polluted molluscs II. Oysters (Ostrea edulis and Crassostrea gigas). Cadmium, zinc and copper, accumulated from polluted habitats by the oysters Ostrea edulis and Crassostrea gagas, were studied. Three distinct low molecular weight (less than 3000 daltons) zinc complexes were separated from highly contaminated C. gigas, one of which may be a complex with the amino acid taurine. Only one of these zinc complexes was present in less contaminated specimens of O. edulis. On gel permeation chromatography of oyster extracts, copper was eluted together with amino acids (principally taurine) and the betaine homarine. No evidence of metallothionein type proteins was found.


Tumor induction in intact and regenerating liver of adult rats by a single treatment with methylazoxymethanol acetate. Methylazoxymethanol (MAM) acetate was given once i.p. to intact adult rats and to rats at 24 h after partial hepatectomy. In each group, tumors developed as early as 10 months. The incidence of neoplastic nodules and of hepatocellular carcinomas in the carcinogen-treated intact adult rats was approximately 70% and, in the rats treated after partial hepatectomy, it was approximately 80%. The data suggest that both dividing and resting liver cells are sensitive to the tumor-initiating effects of methylazoxymethanol acetate.


Selenium inhibition of avian fatty acid synthetase complex. Injection of 0.48 or 0.72 mg of selenium/100 g body weight (as Na2SeO3) into 3-week-old chicks depressed hepatic activity of fatty acid synthetase compared with saline-injected controls. In in vitro experiments with fatty acid synthetase purified to homogeneity, Na2SeO3 was a competitive inhibitor (Ki = ca. 70 micronM). Dithiothreitol (DTT) at low concentrations increased the inhibition of the enzyme by Na2SeO3. At higher DTT concentrations the potentiating effect of DTT on selenium inhibition of the enzyme disappeared. At still higher DTT concentrations, selenium inhibition of fatty acid synthetase was partically relieved. If DTT and Na2SeO3 (2 : 1 molar ratio, respectively) in inhibitory concentrations, were reacted together prior to addition to enzyme and substrate, no inhibition was observed. Potentiation of selenium inhibition of fatty acid synthetase was observed with 2-mercaptoethanol but not with ascorbate. Several organic seleno-compounds were not inhibitory. The data suggest that selenium inhibits fatty acid synthetase by reversible bonding to the sulfhydryl (SH) groups (possibly at the active sites for acetyl-CoA and/or malonyl-CoA binding) of the enzyme. Selenotrisulfide formation involving selenium and the SH groups from the enzyme and thiol compounds is advanced as a possible explanation for the interaction among Se, DTT and enzyme observed in these experiments.


Sterol synthesis. Syntheses of 15-oxygenated 5alpha, 14beta-cholest-7-en-3beta-ol derivatives. Treatment of 3beta-benzoyloxy-14alpha, 15alpha-epoxy-5alpha-cholest-7-ene with boron trifluoride-etherate gave, in 43% yield, 3alpha-benzoyloxy-5alpha, 14beta-cholest-7-en-15-one with the unnatural C-D ring juncture. Reduction of the latter compound with lithium aluminum hydride gave 15alpha, 14beta-cholest-7-en-3beta, 15alpha-diol and 5alpha, 14beta-cholest-7-en-3beta, 15beta-diol in 9% and 81% yields, respectively.


Quantum-chemical and empirical calculations on phospholipids, III. Hydration of the dimethylphosphate anion. The binding of water to the dimethylphosphate anion (DMP-) was calculated using the PCILO method. We found binding energies of 25.95 kcal-mol-1 in the O1-P-O3 plane bridgeing the anionic oxygen atoms and 19.3 kacl-mol-1 for the one-site association of a water molecule to an anionic oxygen atom of DMP-. In this range on water molecule added to DMP- in the O1...O3 bridged configuration has a significantly higher binding energy to DMP- than water molecules added to other binding sites. The total binding energy of 5 water molecules to DMP- is 92 kcal-mol-1, a quantity which is about 10% less than the sum of the binding energies of the corresponding monohydrates.


Configurations of fatty acyl chains in egg phosphatidylcholine-cholesterol mixed bilayers. Based on the structural properties of cholesterol and egg phosphatidylcholine, and on the assumption that the van der Waals' type attactive interaction between the steroid nucleus and the fatty acyl chains provides a stabilizing force for the cholesterol-egg phosphatidylcholine complex, some specific orientation and configurations of the fatty acyl chains around the steroid nucleus in the interacting system are proposed in terms of an optimal packing. The proposed model suggests thathe saturated chains are largely facing the flattened (alpha) surface of the steroid nucleus of cholesterol, while the unsaturated chains can interact with both the alpha and beta surfaces of the steroid nucleus. It is also suggested that the angular methyl groups on the beta surface of the steroid nucleus lock the unsaturated fatty acyl chain in a relatively immobile configuration. Experimental evidence which provides support for the proposed stereochemical model is presented.


Laser Raman studies of molecular interactions with phosphatidylcholine multilayers. I. Effect of iodine-iodide system. The interactions of iodine, iodide and triiodide with phosphatidylcholine multilayers have been investigated in order to find supporting data for conduction mechanisms of iodine-doped bimolecular lipid membranes. On the basis of order-disorder parameters it can be concluded that phospholipid multilayers interact with iodine rather than with its ionic forms. No evidence for the existence of triiodide chains in iodine-doped multilayers has been found. Consequently, the resistance-lowering effect of iodine must be based upon direct iodine-lipid interaction and iodine penetration rather than upon ion transport processes.


Substituent effects on the PMR signals of methyl groups in methyl steroids. Proton magnetic resonance (PMR) signals were assigned to each of the methyl groups for a variety of C-3 oxygenated 4-monomethyl, 6-monomethyl, 4, 4-dimethyl, and 2, 2-dimethyl steroids related to 5alpha-cholestane series. The effects of various substituents (i.e. methyls at C-4, C-6, or C-2, functional groups at C-3, and unsaturated bonds) on the methyl proton resonances have been derived from the assignment. The application of such data to structural and stereochemical problems has also been discussed.


Isosteres of natural phosphates. 5. The preparation of phosphotidycholine, phosphotidylethanolamine and phosphotidylglycerol. Isosteric phosphonate analogues of phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol have been prepared in which the normal oxygen atom of the phosphate ester linkage in the glycerol backbone of the molecule has been replaced by a methylene group. These have been prepared by the coupling of the previously reported phosphotidic acid (isosteric analogue of phosphatidic acid) with the appropriate protected hydroxyl compound mediated by trichloroacetonitrile. In all cases, racemic materials have been isolated: for the analogue of phosphatidylglycerol, a mixture of two enantiomeric pairs is isolated.


Thyroxine and triiodothyronine levels in hyperthyroid patients during treatment with propranolol. Serum triiodothyronine (T3) and thyroxine (T4) levels were measured in twelve hyperthyroid patients before and after treatment with propranolol, 40 mg four times daily, for 2 weeks. There was a significant fall in serum T3 and a significant rise in serum T4 concentrations in the group as a whole and it was concluded that the clinical effectiveness of propranolol in hyperthyroidism may be mediated in part by its action on the peripheral metabolism of thyroid hormones. Propranolol treatment should be withdrawn gradually as removal of the suppressive action of the drug on thyroid hormone metabolism is potentially hazardous, particularly in patients with ischaemic heart disease.


Effect of aminoglutethimide on urinary cortisol and cortisol metabolites in adolescents with Cushing's syndrome. The effect of aminoglutethimide (AG) 4 X 250 mg (670 mg/m2 daily by mouth) on the excretion of the free cortisol (radio-immunoassay) and of its metabolites THE, THF-allo THF, cortolone and beta-cortolone (gas chromatography on capillary column) was studied monthly during 3-5 months in four adolescents (one girl, three boys) aged  15.9-18 years with Cushing's syndrome due to bilateral adrenal hyperplasia, but without evidence of a pituitary tumour. Under AG, all compounds decreased to a minimum after 1-2 months. The decrease of THE- THF-allo THF was most marked, followed by cortolone-beta-cortolone and free cortisol. The sum of the conjugated metabolites was normalized, but free cortisol remained high. A rebound was noted after 3-5 months of continued treatment. This was associated with clinical relapse (weight gain, increasing blood pressure). With AG, a non-steroidal peak appeared on the chromatograms. It is concluded that: (1) AG is only temporarily effective in diminishing the excretion of cortisol and its metabolites; (2) paradoxical increments of 17-ketosteroids as reported from colorimetric analysis are non-specific and are probably due to the non-steroidal peak; and (3) AG appears to modify steroid catabolizing liver enzymes (inhibition of 5beta-reductase and/or 3alpha-dehydrogenase, possibly stimulation of 20alpha- and 20beta-dehydrogenases). This could increase the biological half-life of cortisol and contribute to the clinical rebound, which is due to increased ACTH-secretion. Because of its excellent short-term effects, AG appears to be useful to prepare patients for bilateral adrenalectomy.


Effects of orally administered oestradiol decanoate on plasma oestradiol, oestrone and gonadotrophin levels, vaginal cytology, cervical mucus and endometrium in ovariectomized women. Six ovariectomized women with the uterus left in situ were given a daily oral dose of 0.5 mg of oestradiol decaneoate in oil for 14 days. After a single dose of oestradiol decanoate mean plasma oestradiol rose from 26.8 pg/ml to 66.8 pg/ml within 30 min. There was a further rise to 100-110 pg/ml (P less than 0.001) remaining at the same level over a 24 h period. On repeated daily administration of oestradiol decanoate this rise continued reaching the mean value of 187.1 pg/ml (P less than 0.001) at 2 weeks, while plasma oestrone remained at the same level (147.1 pg/ml) as it was at 24 h. The ratio of plasma oestrone:oestradiol was less than 1 at 2 weeks. Plasma FSH and LH fell progressively during the medication. Changes of the Maturation Index, cervical mucus Ferning and Spinnbarkeit demonstrated the strong 'peripheral' activity of this dose of oestradiol decanoate. All endometrial specimens showed late proliferative changes at 2 weeks. It was concluded that the favourable properties of oestradiol decanoate offer new possibilities for a more physiological oestrogen supplementation therapy.


Influence of presyncope and postural change upon plasma arginine vasopressing concentration in hydrated and dehydrated man. Plasma arginine vasopressin concentrations were measured in five healthy volunteers during postural change under conditions of dehydration and normal hydration. A rise in plasma arginine vasopressin was observed only after dehydration and standing for 40 min. Five further volunteers who developed presyncopal symptoms during orthostasis had exceedingly high plasma arginine vasopressin levels. Changes in plasma arginine vasopressin concentration occurred with no signficant alterations in plasma osmolality.


Penetrance and expressivity of the gene responsible for the Gardner syndrome. The Gardner syndrome is an autosomal dominant condition characterized by multiple polyposis of the colon, associated with various soft- and hard-tissue tumors. Our original kindred, first reported in the early 1950's has been updated and serves as the basis for a discussion of the penetrance and expressivity of the gene responsible for the syndrome. The family consists of 188 members spread over six generations, with 28 individuals clearly documented as having the syndrome. Using two different methods of calculating penetrance, the responsible gene was found to be fully penetrant. This observation was confirmed by an analysis of 160 additional sibships from the literature. This estimation of penetrance is considerably higher than has been previously reported. The expressivity of the gene, however, is quite variable, and this is illustrated using examples from both our kindred and the literature.


Probable dominant inheritance in Blount's disease. A family is described with infantile Blount's disease (tibia vara) following an autosomal dominant mode of inheritance. The bow legs in infancy of family members seem to improve with age, although the literature appears to imply that this is a progressive condition. It is speculated that infantile Blount's disease may be inherited as an autosomal dominant condition with variable penetrance, and that genetic factors have been noted only infrequently, as parents may have improved with age or have been affected only mildly.


Gonadal dysgenesis with 45,X/46,X,dic(Yp) mosaicism. A female patient with a gonodal mucinous cystadenoma on the right side and a gonadoblastoma on the left was found to be a 45,X/46,X,dic (Yp) mosaic. This brings the total number of cases with dicentric Y chromosome reported to date to 23. Together with the available evidence, the information derived from this case supports the hypothesis that the gene on the long arm of the Y chromosome is responsible for the initiation of testicular differentiation, whereas that on the short arm is responsible for the maturation of the testes.


Somatic segregation and Fanconi anemia.

Somatic segregation and Fanconi anemia. A case of Fanconi anemia with terminal acute leukemia is reported. Clones with chromosome abnormalities were observed in bone marrow cells. The patterns of marker chromosome distribution in these clones suggests the occurrence of a somatic segregation mechanism.


Aglossia-adactylia syndrome (special emphasis on the inheritance pattern). Three cases, one with aglossia-adactylia and two with aglossia, are presented, all of whom were born to consanguineous families. Although none of the cases had similarly affected sibs, the possibility of the autosomal recessive mode of inheritance might be taken into account in this syndrome. The dermatoglyphic findings in one previously reported patient showed great similarity to those of one of our cases.


Facio-cardio-renal syndrome: a newly delineated recessive disorder. A previously undescribed genetic syndrome with multiple congenital malformations is described. The major components include: 1) horseshoe kidneys; 2) severe mental retardation; 3) characteristic facies; and 4) heart defects. Evidence for considering it to be an autosomal recessive syndrome is also discussed.


Hypoplasia of the fibula.

Hypoplasia of the fibula. Fibular hypoplasia occurs in differing degrees of severity with fibular hemimelia as its most severe form. Normally the distal epiphyseal plate of the fibula is at the same level as the distal end of the distal tibial epiphysis, whereas the tip of the proximal fibular epiphysis is level with the proximal tibial epiphyseal plate. Varying degrees of shortening of the fibula in relation to the tibia were found in 14 children, 6 of them boys. Shortening at the distal end of the tibia leads to instability of the ankle. Shortening at the proximal end of the fibula leads to hypoplasia of the lateral tibial plateau and valgus deformity of the knee. Syme type ankle disarticulation became necessary in five cases of fibular hemimelia because of leg length discrepancies or ankle instability.


Deformity of the foot following anterior transfer of the posterior tibial tendon and lengthening of the Achilles tendon for spastic equinovarus. Twenty-four children with spastic equinovarus deformity due to cerebral palsy were treated by anterior transfer of the posterior tibial tendon and Achilles tendon lengthening. In five patients, the operation was performed on both sides, making a total of 29 feet available for evaluation after an average follow-up of five years. Only 38 per cent of the results were graded "good" or "satisfactory." Sixty-two per cent were rated as "poor" because of valgus, calcaneus or equinus deformity severe enough to require re-operation. The post-operative deformity was generally evident one or more years after surgery, often progressive, and more disabling as well as more difficult to correct than the original condition. Although the percentage of acceptable results was considerably higher for hemiplegic patients than for others in the study, we conclude that in this group and in all other categories of spastic patients anterior transfer of the posterior tibial tendon should not be performed.


Congenital clubfoot: pathomechanics, Radiographic analysis, and results of surgical treatment. Twenty-one patients with resistant or relapsed clubfeet, ranged in age from four months to 7 years, and all had initially been treated with plaster by board certified orthopaedic surgeons. Surgery was recommended only after an Achilles tenotomy failed to bring the foot into dorsiflexion after approximately four months of age. Surgical correction was based upon the derotation and dorsiflexion of the talus in the ankle mortise. The criteria for a satisfactory result were: no recurrence of the equinus or varus; neutral position of the heel; dorsiflexion of the ankle to at least neutral; a fairly straight forefoot so that the center line of the foot bisected either the second or third toes or passed no further laterally than the third and fourth toes. Of the 33 feet surgically treated, 28 had satisfactory results following the first procedure, and five required additional procedures.


Musculoskeletal abnormalities and ichthyosis. Musculoskeletal abnormalities and the associated findings of ichthyosis were seen in three patients between 1972 and 1975. Review of the literature revealed that musculoskeletal abnormalities had previously been recognized in patients with ichthyosis, but not emphasized because of the more frequent and profound neurological abnormalities. Interestingly, our patients had no neurological abnormalities. Ichthyotics should have thorough musculoskeletal as well as neurological and dermatological examinations.


Multiple joint infections with Enterobacter cloacae. An infant with multiple joint infections from Enterobacter cloacae seems not to have been reported previously. The infant survived, incurred a pathologic dislocation of the left hip, but at 18 months of age was well with all other joints functioning normally.


Fractures in children treated with methotrexate for leukemia. Multiple fractures occurred in 7 children treated with methotrexate for leukemia. Non-union or delayed union in spite of adequate immobilization also occurred in children on methotrexate. When the methotrexate was discontinued the fractures usually healed. Methotrexate appears to be a drug which inhibits osteogenesis, and may be promising in heterotopic ossification and related orthopedic conditions.


Treatment of severe rigid contractures of cerebral palsied upper limbs. Flexion contractures caused by cerebral palsy in adult patients can become so rigid and so severe that skin breakdown and infection on the flexor surfaces of the palm and elbow can result. In 11 such patients we have utilized tendon resections, ray amputations, elbow resection arthroplasties and other techniques to correct deformities. Because improvement of hygiene and not functional rehabilitation was the goal in these patients, these aggressive measures could be utilized more freely than usual without fear of jeopardizing the patient's ability to use the hand post-operatively. Treatment of combined intrinsic and extrinsic contracture usually required resection of the sublimi and metacarpal head resection. Thumb-in-palm deformities were difficult to correct and required osteotomies of the first metacarpal or greater multangular resection. Elbow resection was useful in correcting flexion deformities of that joint but deformity recurred unless the biceps tendon was released as part of the procedure.


Recurrent dislocation of the head of the radius. Traumatic dislocation of the radius at the elbow may be more common than previously appreciated. It may not be diagnosed, or may belatedly be diagnosed as a congenital dislocation of the radial head. Recurrent dislocation does not seem to have been previously reported in the literature.


A review of supernumerary thumb and its surgical management. Type II polydactyly is relatively easy to treat by simple ablation. Central wedge resection is an alternative treatment, providing sufficient bone and soft tissue are excised. Duplication at the MP joint may be difficult to treat because of the frequently associated problems of joint deviation and limited motion, which may produce unacceptable results. MP joint deviation in the ulnar direction of less than 30 degrees does not require treatment. Treatment may be necessary for ulnar deviation greater than 50 degrees. Metacarpal osteotomy, arthrodesis, and central wedge resection are methods of treatment. Collateral ligament reconstruction and tendon transfer were unsuccessful in one patient. IP joint deviation of greater than 15 degrees may need treatment. If there is less than 10 degrees of motion associated with it, arthrodesis is indicated when the joint is skeletally mature. When opposition is impaired thenar muscle tendon transfer is an effective treatment.


Varus derotational osteotomy of the femur in cerebral palsy. Varus derotational osteotomy of the femur is designed to correct coxa valga and femoral anteversion which contribute to progressive hip subluxation and dislocation in certain cases of cerebral palsy. By the application of a careful preoperative evaluation, vigorous postoperative rehabilitation and treatment of complications, satisfactory results were obtained in 17 of 20 patients followed for one to 17 years after osteotomy. No hip subsequently dislocated and dysplastic acetabulae were predictably remodeled in those patients less than 8 years of age.


The surgical correction of congenital elevation of the scapula. A review of seventy-seven cases. Of 77 cases of surgically treated congenital high scapula, the procedure was scapular resection in 36, and scapula relocation in 41. Seventeen had a Woodward-type repair, 14 a Shrock procedure, four cases a Green repair and 6 cases had Petries modification of the Green repair. Follow-up was from two to 14 years with a mean of 11 years. Preoperatively, the mean of shoulder abduction was 90 degrees. Post-operatively, proximal resection increased shoulder abduction to 126 degrees but did not change scapular position. Scapular relocation increased abduction to a mean of 134 degrees and shoulder position was altered from a mean of 1.8 inches of elevation as compared to the normal side, to a mean of 0.5 inches of residual elevation. Significant loss of initial correction occurred in 14 out of 36 cases of proximal resection and 9 of 41 patients with scapular relocation.


Postoperative dislocation in the Charnley and Brunswik total hip arthroplasty. An analysis of 351 total hip arthroplasties according to the method and design of Charnley and 194 Brunswik snap-fit deepened socket design failed to show any significant difference in the incidence of dislocation. Neither were the angulation of the acetabular prosthesis in the anteroposterior projection, time after operation, experience of the surgeon and displacement of the greater trochanter significantly related to dislocation. The variables of significance were anatomical superior-inferior position of the acetabular prosthesis and possibly the number of previous operations on the hip joint.


Unicameral bone cyst in the scapula.

Unicameral bone cyst in the scapula. This is a case report of a 21 year old man with a unicameral bone cyst of the scapula. The occurrence here, as in other flat bones, is rare. The unusual location presents a diagnostic problem, but as in other flat bones, the prognosis after treatment by bone grafting is very good.


A new intramedullary fixation device for the distal third of the femur. A new fixation device was designed for fractures of the distal third of the femur. An additional use has been for the stabilization of supracondylar osteotomies. The device consists of two- pre-shaped rods which are inserted through the medial and lateral femoral condyles into the medullary canal. The proximal end is ductile and the distal end rigid. Cross compression screws through the distal condylar ends anchor the rods and provide additional fixation for inter-condylar fractures. The preliminary experience in 17 patients demonstrates case of insertion and satisfactory internal fixation.


Total knee replacement in hemophilia.

Total knee replacement in hemophilia. Hemophilia produces severe destruction of the knee joint resulting frequently in intractable pain. Total knee replacement with synovectomy can be safely performed with the proper use of blood concentrates. Four Modular knee replacements were performed on three patients without complications, and at follow up of two years or more, the patients were pain free but one had an occasional recurrence of bleeding in the joint.


Bone mineral content and fragility fractures. In 249 patients with fractures characteristic of bone fragility, i.e. femoral neck fracture, vertebral crush fracture, fracture of the upper end of the humerus, Colles' fracture, fracture of the lateral condyle of the tibia and various ankle fractures, and forearm bone mineral content was measured by gamma absorptiometry. Vertebral crush fracture, fracture of the upper end of the femur and fracture of the distal end of the forearm are associated with a generally decreased bone mineral mass. In young women with femoral neck fracture the difference between fracture cases and control cases was greater than in older women. In Colles' fracture, the difference from normal controls was the greatest in the youngest and the oldest women. Bone mass in the forearms is low also in cases of fracture in the upper end of the humerus, of the ankle and of the lateral tibial condyle. In each of the above groups, however, there was so much over-lap between fracture cases and control cases that the measurement of mineral in the forearm cannot be recommended as a very good tool for determination of fracture susceptability in individual subjects.


Fluoride in the prevention of osteopenia: studies of the skeletal mass in calcium deficient rats. Growing rats, five weeks old and weighing 80 g at the beginning of the experiment, during 30 weeks were given a normal diet and distilled water with, in one group, a fluoride supplement of 50 ppm. During this period all animals gained weight similarly. The skeletal mass of the fluoride treated animals became slightly but siginficantly larger than that of the controls. After 30 weeks half of the animals were given a calcium deficient diet for another 16 weeks. Osteopenia developed regardless of a simultaneous fluoride supplement. However, animals given fluoride during the initial 30 weeks only, did not lose bone during the subsequent period of calcium deficiency. Conceivably, fluoride could be a long-term preventative measure but should not be considered a therapeutic agent alone.


The effect of chronic heparin administration on the mineralization of an experimental osseous defect. Adult roosters with experimental circular osteotomy defects in the metatarsus were placed on chronic heparin therapy. In vivo measurement of bone mineral content changes of the osteotomy using Iodine-125 show no adverse affect of heparin treatment on remineralization. However, the weight of dry-defatted femurs was decreased and suggests that there was significant heparin-induced systemic bone demineralization.


The effects of zinc deprivation on the host response to intramuscular bone matrix implants in the rat. Sterile sequentially extracted insoluble bone matrix gelatin and freeze-dried allogeneic demineralized whole bone matrix was implanted into a lumbar muscle pouch of 12 Sprague-Dawley rats fed a diet containing 0.9 ppm zinc and into 6 rats fed a diet containing 50 ppm zinc. Histological sections and microradiography demonstrated that skeletal tissue induction occurred in all instances. In the zinc-supplemented hosts, four weeks postimplantation, trabecular bone and bone marrow grew on both sides of the matrix implant which had been almost completely resorbed by matrixclast activity. However, in the zinc-deficient hosts, the central cavity of the matrix was first filled with mesenchyme and then cartilage cells which grew in the form of thin wedges into the implanted matrix. Poor vascularization appears to be an important factor in cell proliferation and abnormal differentiation in zinc deficiency.


Experimental arthritis in rabbit knees: a study of relief of pressure on one tibial plateau in immature and mature rabbits. The Hall model of experimental arthritis of the knee (excision of the lateral femoral condyle) offers a unique way of investigating the earliest changes of degenerative arthritis. Predictable degeneration of the lateral tibial plateau occurs when there is lack of contact with an opposing surface. Previous work by Hall and Thompson has not concentrated upon the early changes in proven mature animals of optimum age for a study of simulated osteoarthritis. In this work using mature rabbits, two important findings are documented. The earliest observed change in the joint, beginning at 7 days is loss of matrix protein-polysaccharides from the lateral plateau, with no evidence of change in the subchondral bone until much later; in this respect mature differ from immature animals. Furthermore, there is strong evidence for late (three to 6 months) protein-polysaccharide synthesis in the previously degeneraing articular cartilage in which the residual cells reconstitute an effective matrix.


Hematogenous osteomyelitis of the clavicle in children. Recognition of acute hematogenous osteomyelitis of the clavicle can be difficult. The condition may even to confused with fracture or malignancy. Treatment with parenteral antibiotics must be continuous for at least three weeks. If there is evidence of abscess formation, incision and drainage is indicated. If surgery is performed, a thorough debridement or partial resection may be required to prevent recurrence. If inadequately treated, the process becomes chronic. Resection of involved portion of the clavicle has been effective in the chornic stage of the disease. In the young child the resected segment often regenerates and the clavicle completely reconstitutes itself.


Voluntary subluxation of the acromioclavicular joint. A case report. This is a case report of a 19-year-old girl with bilateral voluntary subluxation of the acromioclavicular joint, a condition which seems not to have been described in the literature. The complaints of pain were avoidable by desisting from habitual movements that subluxated her shoulders.


Hereditary arthro-ophthalmopathy (the Stickler syndrome). Report of a kindred with protrusio acetabuli. Hereditary Arthro-ophthalmopathy (The Stickler Syndrome) is a relatively common dominantly inherited disorder of connective tissue. A wide range of musculoskeletal involvement occurs including marfanoid habitus, kyphosis, scoliosis, slipped epiphyses, joint laxity and degenerative arthritis. Congenital myopia and micrognathia are the most characteristic non-skeletal features. An affected family is reported who also exhibit protrusio acetabuli. It is important to recognize this syndrome for both diagnostic and therapeutic purposes.


Congenital deficiency of the extrinsic extensor mechanism of the hand. In a 16-year-old girl, congenital extensor deficiency of the hand with absence of true clasping of the thumb was transmitted by an autosomal dominant mechanism of inheritance. The age of presentation was more advanced than usual. This case is the basis for proposing an hypothesis that the condition is a manifestation of a failure of innervation to develop in the extensor muscles of the forearm.


Harrington rod distraction instrumentation: its effect on vertebral rotation and thoracic compensation. The effects of Harrington rod distraction instrumentation on vertebral rotation and thoracic decompensation were investigated radiographically both pre- and post-operatively. A method for semiquantitatively evaluating thoracic decompensation is introduced to serve as an adjunct to the evaluation of spinal deformity. Although little derotation of the vertebrae occurs with lateral correction, thoracic decompensation should be significantly improved.


Delayed paresis following spinal fusion with Harrington instrumentation. Immediate postoperative paresis following spinal fusion for scoliosis is uncommon. This neurological disaster can occur either within hours or days after surgical correction of the curvature. Paresis of the right lower extremity occurred on the third postoperative day in a 15-year-old boy who underwent spinal fusion for a pseudarthrosis of a previous fusion and in whom a Harrington rod was inserted for stability but not correction. The rod was removed within four hours of recognition of the paresis; within 18 months the child made an almost complete recovery of all motor function; slight residual weakness of the anterior dorsiflexors of the foot still remain.


Long-term follow-up of Perthes' disease treated nonoperatively. Forty-six patients with Perthes disease treated nonoperatively were reviewed 10 to 43 years later. The median follow-up was 17 years. The patients were analyzed according to sex, age of onset, quantity of head involvement, type of treatment, duration of treatment, functional end result based on the Harris hip scale, and anatomic end result based on Mose templete evaluation. Most patients were treated with an ischial weight-bearing brace. The anatomic results of this treatment tended to be poor, probably worse than no treatment at all. In general, poor results were correlated with late onset, greater quantity of head involvement, and lateral subluxation of the femoral head. As reported in other series, the anatomic results did not correlate well with the functional results, only two patients having Harris hip scales below 70.


Avascular necrosis of the capital femoral epiphysis in a child receiving corticosteroids: a case report. Exogenous steroids are known to induce aseptic necrosis in the femoral head of adults. This case report of a 9-year-old girl with corticosteroid induced femoral head necrosis demonstrates effective treatment with an abduction device in a manner similar to that prescribed for the treatment of Legg-Calve-Perthes disease.


Double contrast knee arthrography in children. The indications for knee arthrography in children consist of: suspected internal derangement; osteochondritis dissecans; Blount's disease; popliteal cysts; loose bodies; synovial tumors; and miscellaneous abnormalities including unexplained knee pain.


Tibial lengthening: a preliminary report. A preliminary review of 9 tibial lengthenings has been made to assess the value of a modification of the Anderson operation. The procedure can be carried out in one stage and is applicable to the older child and young adult. This is important as it may be used in the late or neglected case where epiphyseal arrest has failed or was never done. Five out of 9 patients in this series were skeletally mature. Leg lengthening procedures will always entail certain hazards. Complications occurred in 7 of the 9 patients, but were recognized early and expeditiously managed, and in several instances resulted in only minor deformity. The satisfactory end results in this series are attributable to the principle of limiting tibial lengthening to no more than 10 per cent of the overall bone length, i.e. 5 cm or less. No neurovascular complications occurred. Although tibial lengthening is hazardous and can cause severe disability, the results reported here suggest that in selected cases, it is a valuable procedure for correction of leg length discrepancy.


Distribution of constitutive heterochromatin in carnivores. The distribution of constitutive heterochromatin (C-banding) in the genomes of nine species of Felidae, one species of Mustelidae, two species of Procyonidae, one species of Viverridae, one species of Canidae, and one species of Ursidae has been studied. In the chromosomes of several felid species the C-band is apparently absent. A few chromosomes show only telomeric staining in one arm or sometimes in both arms. Centromeric and interstitial distribution of heterochromatin has also been demonstrated in other species of Carnivors, but, in general, the C-banded material in felids is comparatively less in amount, and more weakly staining, than in other mammals. Induction of C-banding patterns in certain carnivore species is rather difficult, probably because of the minimal amount of heterochromatin present.


Training disadvantaged preschoolers on various fantasy activities: effects on cognitive functioning and impulse control. Preschool children were trained in 1 of 3 different types of fantasy activities over a school year. The effects of this training were evaluated over a variety of tasks measuring cognitive development and impulse control. The same basic experiment was replicated over 3 different years. Results indicated that physical enactment of fantasy experiences (viz., acting fairy tales or enacting previous experiences) had a sizable effect on many of these variables; while simply listening and discussing was often no more effective than the control condition that merely cut, pasted, etc. Evidence suggested that fantasy play remoter from reality was more facilitative for development than more realistically oriented fantasy play.


Swallowing and the organization of sucking in the human newborn. The effect of varying amount and concentration of a sucrose solution on swallowing and sucking activity of newborns was studied. Swallowing activity increased relative to the number of sucks, and sucking rate slowed as amount and concentration of sucrose was increased. Sucking interresponse times associated with swallowing were approximately 200 msec longer than interresponse times not associated with swallows. The results are discussed in relation to previous studies of sucking in the newborn.


Self-reinforcement in high- and low-aggressive boys following acts of aggression. Preadolescent boys either high or low in characteristic level of peer-directed aggression were initially annoyed by a peer confederate and then delivered aversive auditory stimulation to him via headphones. Half the boys of each aggression status were led to believe that they had injured their victim, through high pain-cue feedback, whereas the other half were given low pain-cue feedback. Subsequently, boys self-dispensed rewards with instructions to take what they deserved for what they had done to the other boy. Low aggressive boys severely curtailed their self-reinforcement following high pain cues, whereas high-aggressive boys did not. Results supported the view that high-aggressive boys fail to experience the negative self-reactions following injurious behavior that are experienced by boys lower in aggressive tendencies.


Localization of sequences specifying messenger RNA to light-staining G-bands of human chromosomes. Total cytoplasmic polyadenylated RNA was isolated from the human lymphocyte cell line Wil2 by oligo(dT)-cellulose chromatography. Tritiated complementary DNA (cDNA) was transcribed from the RNA and used as a probe for in situ hybridization to metaphase chromosomes. The majority of G-negative or lightly staining bands were found to be preferential sites of hybridization.


The location of DNA homologous to human satellite III DNA in the chromosomes of chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orang utan (Pongo pygmaeus). Radioactive RNA with sequences complementary to human DNA satellite III was hybridised in situ to metaphase chromosomes of the chimpanzee (Pan troglodytes), the gorilla (Gorilla gorilla) and the orangutan (Pongo pygmaeus). A quantitative analysis of the radioactivity, and hence of the chromosomal distribution of human DNA satellite III equivalent sequences in the great apes, was undertaken, and the results compared with interspecies chromosome homologies based upon Giemsa banding patterns. In some instances DNA with sequence homology to human satellite III is present on the equivalent ("homologous") chromosomes in identical positions in two or more species although quantitative differences are observed. In other cases there appears to be no correspondence between satellite DNA location and chromosome homology determined by banding patterns. These results differ from those found for most transcribed DNA sequences where the same sequence is located on homologous chromosomes in each species.


Effect of cycloheximide on RNA synthesis in Chironomus polytene chromosomes. Modifications in the synthesis of salivary gland RNA were induced by treatments with 10 microgram/ml cycloheximide (CHM) on 4th instar larvae of Chironomus pallidivitattus. After 3, 6 and 24 h CHM treatment, RNA was labeled "in vitro", by incubating the salivary glands in a medium containing H3-uridine. The electrophoretical analyses corresponding to the 3 and 6 h treatment showed a stimulation of the non-ribosomal components of the newly synthesized RNA, while preribosomal RNA synthesis appeared depressed. This fact was also confirmed at cytological level, since autoradiograms made after 3 h of CHM treatment showed a reduced H3-uridine label over the nucleolus and an increase of diffuse labeling over the chromosomes. Longer treatments (24 h) causes a considerable inhibition of the synthesis of all RNA species. The role played by protein synthesis inhibition in the aforementioned effects is discussed.--Some of the morphological implications of CHM treatment, such as modifications of the nucleolar structure (nucleolar segregation) are also reported. The use of a squash technique based on glutaraldehyde fixation of the salivary glands, considerably facilitates such studies.


Purification and characterization of two transcribed repetitive DNA fractions from the pigeon genome. Two fractions of the repeats belonging to intermediate frequency repetitive DNA were isolated from the total pigeon nuclear DNA fragmented to about 450 nucleotides. One fraction was designated as "rare repeats" (repetition frequency about 35 per haploid genome) and another termed as "moderate repeats" (repetition frequency about 2500 per haploid genome). The rare repeats, which constitute about 7% of the total DNA, include at least 75% of the repetitive DNA sequences transcribed into the high molecular fraction (greater than 45S) of HnRNA in erythroid cells. These repeats have properties compatible with the characteristics of the class of low frequency interspersed DNA found in genomes of many other Metazoan species. The moderate repeats contribute only about 10-20% of the total repetitive DNA copies present in greater than 45S HnRNA and differ from the rare repeats in some other properties.--The possible role of the rare repeats in the genome is discussed.


Cytological evidence of male heterogamety in sex determination of Telmatoscopus albipunctatus (Diptera: Psychodidae). Telmatoscopus albipunctatus is polymorphic for several polytene chromosome bands. In examining the inheritance of a polymorphic heterochromatin-like band in chromosome IV we verified that it is inherited like a sex-linked factor. There are two types of chromosome IV in regard to this band: one bears a very thick heterochromatin-like band (H+), and the other bears a thinner corresponding band (H-). Three kinds of combinations are found in our stocks: H+H+, H+H- and H-H-. All three combinations can be found in females; however, in males, only the combinations H+H- and H-H- are found. Through specific crosses, it was concluded that the sex determining factor is located in chromosome IV in close vicinity to these bands.


Developmental puffing patterns in salivary gland chromosomes of Rhynchosciara hollaenderi. An analysis of puff formation and regression has been carried out in 3 morphologically distinct regions of the Rhynchosciara hollaenderi salivary gland during mid-larval through pupal development. Puffing differences among these 3 regions have been found and analysed for both trna and DNA puffs. The presence of such differences suggests that the gland regions may also be functionally differentiated. - Developmentally specific sequences of puffs have been distinguished and correlated with morphological and physiological events which occur during the development of Rhynchosciara. The DNA puffs as well as the RNA puggs enlarge and regress at predictably specific developmental stages. The presence of particular puffing sequences in the late larval to pupal period has been compared with the occurrence of known changes in the developmental ecdysone titre for Rhynchosciara. Certain aspects of this developmental picture appear to fit the ecdysone-stimulated puffing model for Drosophila, but other aspects indicate that the tdrosophila-based model may not be completely applicable to Rhynchosciara.


Puffing activity in the salivary gland chromosomes of Rhynchosciara under experimental conditions. By using the techniques of ligation of the larvae (brain and endocrine glands extirpation) and salivary gland implantation, the hormonal dependence of the activity of certain puffs of Rhynchosciara was investigated. Our results have shown that the puffing behaviour--activation and deactivation--varies according to the developmental stage in which the larvae were ligated. When the larvae were ligated just before the drastic changes in the puffing pattern, which occur prior to pupation, these changes fail to occur. When the larvae were ligated after the onset of these changes we have observed: a) some of the puffs active at the time of the ligature regress promptly, earlier than their normal timing observed in controls; b) others remain active indefinitely and c) there are still some which regress accordingly to the normal timing. The puff B2 which behaves as those in b was double checked by means of implantation experiments. Salivary glands which had puff B2 at its maximum expansion were implanted into younger larvae and that puff also remained active in the body cavity of these larvae. Hypotheses to explain the results obtained are discussed.


Patterns of disjunction frequencies in heterozygous reciprocal translocations from the German cockroach. Metaphase I cells from heterozygotes in eight reciprocal chromosome translocation stocks of Blattella germanica (L.) have been examined and counted. The data show that three stocks have random disjunction (adjacent and alternate orientations are equally frequent), but the cell types adjacent-1, alternate-1, adjacent-2, and alternate-2 are present in a ratio of 2:1:1:2. Four stocks with directed disjunction have similar patterns, except for a heavy preponderace of alternate-2 cells. This difference is reflected in the finding that 60-65% of all cells in these interchanges are type II cells (alternate-2 plus adjacent-2), and individual percentages agree closely with percent directed disjunction is distinctly different in that the frequencies of both alternate-1 and alternate-2 cells are elevated and contribute to directed disjunction. It has also been demonstrated with two stocks that changes in disjunction frequencies can be brought about by genetic manipulation. These observations provide a better understanding of the differences between random and directed disjunction.


The circadian rhythm of rat motor activity and the effect of brain monoamine inhibitors (PCPA and nialamide). The study of the circadian motor rhythm in free-running conditions of 500 g rats during 6 successive days shows that the endogenous period of the rhythm in these conditions is 23.40 hrs. The two poisons studied (PCPA in 40 mg/100 g dose and nialamide 5 and 10 mg/100 g doses) have both a deep effect on the functioning of the endogenous rhythm. PCPA reduces the amplitude of the increase of night over day activity to a fourth of the control value. The reducation may be attributed either to increased day activity or to reduced night activity. Nialamide reduces the amplitude of this increase to 80 or 70/100 of control value; this was observed with 5 or 10 mg nialamide/100 g body weight. The most important effect of nialamide on the endogenous rhythm lies in the disappearance of the regular shortening of nearly 20 min of the endogenous rhythm in DD conditions. The abrupt transition for LD 12:12 conditions to DD disturbs the endogenous period for 24 hrs.


Nonstationarity in human perceptual ultradian rhythms. Thirty subjects tests on the SAE for 8 hrs during morning and evening periods demonstrated significant ultradian rhythms in perception. The perceptual rhythms were nonstationary with respect to 1) the frequency of the rhythms reflected in some slowing of the rhythms during the course of the testing period, and in frequency differences between the morning and afternoon rhythms, and 2) the level of the illusion reflected in abrupt shifts in the magnitude of the SAE during the course of the testing period without subsequent recovery.


Circadian study on serum gastrin in patients with duodenal ulcers and in a control group. Two groups of subjects (one consisting of fourteen apparently healthy subjects, the other of fourteen patients with peptic ulcers) were kept for a least 7 days on the same living schedule (nocturnal sleep for 22(00) to 05(00) and meals standardized at 08(00)-08(30), 12(00)-12(30), 17(30)-18(00)). During 24 hors, samples of venous blood were obtained from each subject every 4 hours for the serum gastrin radioimmunoassay. The results were analyzed by mean cosinor method. The control group has a statistically significant circadian rhythm, while we were not able to detect a circadian rhythm in the patients with duodenal ulcers. The daily mean of serum gastrin levels appears to be significantly reduced in the ulcer group.


Towards a typology of relapse: a preliminary report. This paper outlines an empirical investigation into alcoholic relapse. The model underlying this work hypothesized that relapse in alcoholics is an interaction between (1) situations seen as dangerous in precipitating relapse, (2) the behaviours available within the individuals' repertoire to cope with these situations, (3) the perceived effectiveness of these "coping" behaviours and (4) the degree of alcohol dependence. The results of a "principal components" analysis indicated that "dangerous situations" or relapse precipitants could be categorized as (1) an unpleasant affect, (2) external events and euphoric feelings, (3) social anxiety and (4) lessened cognitive vigilance. Except for "external events", these relapse precipitants seemed to be associated with certain styles of coping, with varying degrees of effectiveness. The therapeutic implications of these findings are discussed in the context of designing treatment regimes geared towards more effective coping behaviours given specific types of situations.


[An alcohol contact program: training for increased security of alcoholics in trial situations]. Alcoholics who have taken the decision to abstain are known to develop, partially out of fear of a relapse, an almost phobic avoidance behaviour towards situations where alcoholic drinks may be proffered. Starting from this observation a four-hour behavioural programme, involving modeling and the discussion of appropriate behaviour, was developed to prepare patients for such situations. The two methods resulted in equally highly significant improvement, as measured both by self-assessment and by the assessment of independent observers.


The pharmacology of drug abuse--a novel approach to drug education at San Quentin. A novel and successful undergraduate-level course in pharmacology has been established as part of the drug education program at California's San Quentin State Prison. The program was designed to create a two-way teaching--learning experience between former drug abusers and their teachers, all of whom were doctoral candidates and post-doctoral scholars in pharmacology at a nearby university medical center. In reviewing the pharmacology of psychoactive drugs, the emphasis was on the principles of drug action in the central nervous system, with additional attention to those factors that contribute a potential for abuse. An attempt was made to present information in a strictly objective and non-prejudical manner. An initial analysis has shown a possible change in attitude among the student-inmates toward drugs of abuse. It is likely that courses following a similar design would be well received and successful in any type of undergraduate program that addresses the subject of drug abuse.


[The value of stimulation of the renin-angiotensin-aldosterone system as a screening test for hypertension (author's transl)]. Renin activity, angiotensin-II concentration and venous aldosterone concentration were measured in 20 healthy subjects and 18 hypertensives before and after stimulation of the renin-angiotensin-aldosterone system. The test did not distinguish between the two groups: in the individual case there was no relationship between renin-activity, angiotensin-II concentration and aldosterone concentration in peripheral venous blood. Stimulation of the system without sodium balance is not a reliable screening test for hypertension.


[A simple and reliable atrial pacemaker electrode: technique of transvenous implantation and clinical results with a metal hook electrode (author's transl)]. At present only about 1% of all implanted pacemakers are atrial triggered ones, although an indication for them exists in about 77% of cases. This disproportion is due to an overestimate of the difficulties encountered in fixing the electrode. The electrode developed by Irnich has now been modified to provide good fixation for atrial stimulation, as well as recording of atrial potentials. Preliminary results in 20 patients have been favourable. Over a seven-month observation period there have been no instances of dislocation or loss of effective stimulation.


[Emptying of goitre cysts by small-needle aspiration (author's transl)]. Small-needle aspiration was practised up to 16 times (average 2.7 times) in 89 patients with cystic thyroid nodules. Re-examination 7 days to 22 months later showed that the nodule had disappeared or the amount of cystic fluid had decreased to 30% or less in 32 patients. All patients also received suppressive doses of thyroid hormones. It is suggested that additional injection of sclerosing fluid into the cyst may improve results further.


[Cytogenetic paternity test in father-daughter incest (case report) (author's transl)]. Cytogenetic test for paternity proved superior to serological tests in a case in which possible father-daughter incest was to be proven or disproven. Of seven fetal chromosomal markers three were derived from the putative father, two from the mother and two paternal markers were present in both fetus and mother as a consequence of the incest. The fetus was homozygous for a paternal marker on chromosome 22.


[Early digitalisation of patients with arterial hypertension (author's transl)]. Haemodynamic tests were performed at rest and during exercise in 41 patients with arterial hypertension and early impairment of left-ventricular function, before and after administration of a single dose of 0.6 mg beta-methyl-digoxin. After clinical, ECG and coronary-angiographic studies, the patients were assigned to two groups. Group I: 17 patients with transmural infarcts in the chronic stage or with angina. Cardiac output was within normal limits at rest and on exercise and was not significantly altered by administration of beta-methyl-digoxin. There was no significant fall during exercise of the abnormally elevated pulmonary "wedge" pressure or of other pressures in the lesser circulation after digitalis. Group II: 24 patients without signs of coronary heart disease. They, too, had a normal cardiac output at rest and on exercise, not significantly changed by digitalisation with beta-methyl-digoxin. But pulmonary "wedge" pressure and right-atrial mean pressure were significantly reduced during exercise. Before beta-methyl-digoxin the mean "wedge" pressure rose on exercise to an average of 27.3 +/- 5.4 mm Hg, but after beta-methyl-digoxin to only 21.7 +/- 5.1 mm Hg (P less than 0.001). The mean right atrial pressure changed similar. These results indicate that acute digitalisation at the stated dosage in general has an effect on abnormal myocardial function only if there is no additional coronary heart disease.


[Myxoma of the left atrium (author's transl)]. Clinical picture, course and routine cardiological diagnostic methods may give important clues indicating the presence of myxoma of the left atrium, but a definite diagnosis can only be made using echocardiography or cineangiography. The former is free of risk and thus should always precede the latter. Three patients were observed with a stalked myxoma of the left atrium which could be demonstrated echocardiographically. Every proven myxoma should be operated on as soon as possible as otherwise sudden unexpected complications leading to death may occur. In patients with changing cardiological signs and changing clinical symptoms this tumour should be excluded promptly by echocardiography. Necropsy statistics do not accurately reflect the incidence.


[Innervation of the m. sphincter pylori in cats]. The ultrastructure of neuro-muscular relations in m. sphincter pylori of a cat was examined by fixation with CsO4 using imersion and staining of a sample of tissue with uranyl acetate during delydration. There were regular, dense and parallel muscular cells with intersticial spaces in the range of 250 A. Structures with various round and oval forms fitted closely to the smooth muscle cells. They had homogeneous amorphous structure and small electronic density. Nervous bundles with variable size were located in the intersticial spaces. Isolated single nervous fibres were encountered at some sites. Axonic profiles were located from the plasmatic membrane of the muscular cells at a distance of least 430 A. There were contacts with structure similar to the synapses among isolated nervous profiles. There were also nervous profile which contained large (around 1500 A) granular vesicules. The author discuses the type of inervation of m. sphincter pylori as well as the vesicular content of axons.in view of the eventual functional significance.


[Symmetry and asymmetry of the orbital opening in Bulgarians]. The authors examined 412 skulls of grown up individuals of male sex and 15 dimensions were measured for aditus orbitae. The data were prepared biostaticaly both for the most important six and for the orbital index amd orbital entrance. The dimensions showed equal size at both sides in considerable, but various for the single numbers of skulls (1/5 up to over 1/3). In the majority of the remaining skulls the absolute differences were small in favour of the one or the other side (1--2 mm). The width of the entrance was in most cases (63%) larger in the right with mean value of the differences of 1,72 mm, but the height-on the left of the average with 1,41 mm. Hamachonchia was encountered more frequiently on the right, but hypoikonchia-on the left. The dimensions, which passed through the orbital entrance transversly (three dimensions) and obliquely (one dimension) had larger values more frequently on the right.


[Pathomorphological and histochemical changes in the intestines of white rats due to low-frequency vibration]. The authors carried out experiments on animals (40 white male rats) which were subjected to daily a two-hour action of the common vertical sinusoidal vibrations with a frequency of 20 Hr (I group) and 50 Hr (II group) with acceleration of 22,0 m/sec2 for a period of ten days (I group--A and second group--A) and 30 days (I group--B and II group--B). Histomorphological and histochemical methods were used and the authors found changes in microcirculation and structure of the intestinal wall manifested in the animals of the II group. The obtained results were in support of the clinical data on the disturbances in intestinal function in patients with vibration disease and corresponded to the experimental data on the occurrence of vascular and dystrophic changes in the internal organs under vibration action.


[Morphology of the spleen and immune response in experimental nutritional deficiency in rats]. The author examined 60 white rats of the strain "Wistar" with initial age of four months and body weight of 180--220 gm, subjecter to nutritive deficit regimens with various protein content. He described the morphological changes in the spleen, made a qualitative analysis of IgG and IgM in serum and examined also some links of the immune response after antigen stimulation with human gamma-globulin. Very limited nutrition (5,74 of protein) for 16 weeks caused immune deficit with definite morphological substrate-atrophy and fibrosis of the lymphoid tissue. Moderate limited feeding (11, 48% of protein) did not induce substantial deviations from the functions the immune system.


[Influence of taliblastin and vinblastine on serum agglutinins determined by 2 methods]. The authors examined the influence of the potential antitumorous preparation taliblastin and the well known cytostatic vinblastin on the formation of serum agglutinins in mice. Two methods were used--the classical reaction of agglutination and the method for inhibition of passive migration of erythrocytes (IPM) described by Schweicer and Gilisen (1974). It was established that vinblastin markedly inhibited the formation of specific agglutinating antibodies, while taliblastin was considerably weaker immunosupresor; The method of IPM was more sensitive than the classical reaction of agglutination and gave a possibility for better determination of immunosuppresive action of cytostatics.


[Comparative studies of enzyme-inducing ability of phenobarbital, methylphenobarbital, glutethimide and their N-substituted morphoalkylic derivatives]. The authors examined the capability of N-substituted morpholinoalkyl derivated of phenobarbiral methylphenobarbital and glutetimide to induce drug-dissimilated enzymes in liver microsomes as those newly syntesized compounds were compared with the initial substances, which were enzyme inductors. They examined the following indices: duration of hexobarbital narcosis after a six day treatment of male white rats with one of the substances liver weight, related to the percentage of the whole body weight, protein content in liver homogenates and in microsomal fraction of liver, the activity of N-demetilase in liver. There was a considerable shortening of the duration of hexobarbital sleep due to barbiturates, more manifested in animals, treated with methylphenobarbital. Glutetimide shortened the narcosis statisticaly insignificant. The respective morpholonoalkylic derivatives not only did not shortened the narcotic sleep, but even slightly prolonged. it. The liver weight of the rats, treated with barbiturates, was increased with 25--30% while that of the rats treated with morpholinoalkylic derivatives did not differ from the liver weight of the control animals. The protein content in liver homogenates did not show statistically significant differences in the single groups. The protein content of the microsomal liver fraciton was increased in the animals, treated with barbiturates and glutetimide, while in the rats, treated with morphoalkylic derivatives the protein content did not differ from that of the controls, but it was even reduced after treatment with a derivative of glutetimide. Phenobarbital and methylphenobarbital increased significantly the activity of pyrimidone N-demetilase, while their N-substituted morpholinc-alkyli derivatives inhibited it.


[Effect of Bulgarian preparation, Nivalin, on bioelectrical activity of the ureter]. The authors examined the influence of the Bulgarian preparation Nivalin on the bioelectrical activity of practicaly healthy ureters of cats under the conditions of acute experiment. They used on the average 1,5--2 mg of Nivalin per kg of body weight as the whole amount was used singly and administered intravenously. They found that Nivalin caused the appearence of more frequent bioelectrical complexes of ureters, which in most cases was manifested in two phages--the first almost 1--15 minutes after the injection and the second-after 60--90 minutesmthere was also an improvement of the rhythm of the bioelectrical activity and amplitude changes in bioelectrical complexes. There was stabilization of the obtained effects around two hours after administration of Nivalin under the conditions of the experiment. The authors consider that in this direction the experiments should be continued and should be examined practicaly the therapeutic effect of Novalin on persons with disturbances in the dynamics of urinary pathways.


[Study of the dithiocarbamate-basfungin, action on the body of pregnant white rats]. The authors carried out experiments on 120 pregnant rats and treated them oraly with basfungin in daily doses of 1/13 of LD50--1/100 of LD50. They examined the activity of serum enzymes-cholinesterase, glutamat-oxalacetic and glutamatryuvic transaminases, alkaline phosphatases, lactatdehydrogenase; in liver homogenates. They determined the content of sulphydryl and disulphide groups, cytochromexidase activity as well as pathomorophological studies on liver, thyroid gland, trachea, lung, myocardium, spleen and kidneys. There was reduced activity of cholinesterase, glutamatpyruvic transaminase, lactatdehydrogenase and elevated activity of alkaline phosphatase; inhibited activity of cytochromoxidase and reduced content of sulphydryl and disulfide groups in liver. The changes revealed marked dependence between dose and response. There were pathological findings only in liver, presenting manifested parenchymatous distrophy involving hepatocytes centraly located after administration of 250 mg of basfungine per kg of bogy weight, but after administration of 125 mg per kg of body weight there was only acute venous stasis.


[Biochemical characteristics of soluble collagen in glued and sewed liver wounds]. The author examined soluble fractions of collagenalkaline soluble, acid soluble and neutral soluble in sewed and glued with cyanacrylic glue experimental wounds of liever in rabbits. The operative wounds were treated as regenerating tissues with various metabolism in respect to the soluble collagen. There was higher percentage ratio of the fractions revealing the synthesis of the collagenous molecule and the formation of colagemous fibre in the sewed wounds.


[Model of formation of chronic volume loading in the right heart]. The authors describe an experimental model for examining the changes occuring in the haemodynamics of the small circuit as a result of created artificial defect of the interatrial septum. An original operative technique is used, by which the complete clamping of the right lung artery and vera is avoided and lung complications are prevented. The performed control haemodynamic studies up to one vear after the operation support the efficiency of the proposed model.


[Age characteristics in vascularization of the intestinal mucosa]. The authors examined age peculiarities in the microcirculation bed of the intestinal mucosa in 20 individuals, aged from 0 to 83 years. The vessels were manifested by injection with Indian ink-gelatine mass. There was also complication of their angioarthitectonics parallel to the age and progressive thickening of glandular layer and enlargement and clongation of the villi. The arterial sources were increased and varified. Villus-capillary nest was changed in vertical direction. Togethe with this the outflow venous system was complicated as over the basal plexus a second venous plexus was formed-over the basis of the villi. The mucosa was enriched with arterio-venous anastomosis. Maximal development of the microcirculatory system was found at the end of the third decade, after which their reduction begins. This process was more manifested after the  sixth decade, when the blood vessels were folded and received uneven constructions and dilatations, and then the capillary nest is rearranged and simplified.


Dog liver 3-hydroxy-3-methylglutaryl coenzyme A reductase. A rapid and sensitive assay method for 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-coA reductase, EC 1.1.1.34) is described. HMG-coA reductase is demonstrated in dog liver microsomes, and the converted reaction product has been identified as mevalonolactone. The enzyme activity undergoes cyclic variation and increases by more than tenfold 5 h after feeding. The properties of dog liver enzyme are generally similar to the rat liver enzyme in the method of solubilization, cold inactivation, pH optimum, and Km values.


Isolation of human trypsin by affinity chromatography. A method is described to prepare an affinity adsorbent for human trypsin by coupling bovine pancreatic trypsin inhibitor (Kunitz) to CNBr-activated Sepharose. The highly selective adsorbent permitted the rapid isolation of trypsin from an activated extract of human pancreas. The trypsin obtained was completely free of chymotryptic activity and of sufficient purity to serve as a standard for the development of a specific radioimmunoassay for human trypsin.


Purification and characterization of human hypoxanthine/guanine phosphoribosyltransferase. Human hypoxanthine/guanine phosphoribosyltransferase (EC 2.4.2.8) was purified from red blood cells by the following two methods. Method A includes (a) elimination of hemoglobin by DEAE-cellulose, (b) DEAE-Sephadex chromatography, (c) specific elution of the enzyme from CM-Sephadex by pyrophosphate and (d) Sephadex G-100 gel filtration. Method B includes (a) elimination of hemoglobin by DEAE-cellulose, (b) acid treatment at pH 4.5, (c) ammonium sulfate fractionation, (d) DEAE-Sephadex chromatography, (e) heat treatment at 85 degrees C and (f) Sephadex G-100 gel filtration. Homogeneous enzyme preparation was obtained by the two methods with 8000-9000-fold purification. The sedimentation coefficient (S20,w) was 5.5--5.6 S, and the molecular weight of the enzyme was estimated at about 85000 by the sedimentation equilibrium method. The subunit molecular weight of the untreated protein and S-carboxymethylmaleyl protein was estimated as 41000--45000 by the sedimentation equilibrium method in the presence of guanidine hydrochloride. However, the subunit size estimated by the sodium dodecylsulfate gel electrophoresis was only 26000. Amino acid composition of the enzyme was determined. Glucosamine, sialic acid and hexose were not detected in the enzyme.


Diacylglycerol acyltransferase from rat liver microsomes. Separation and acyl-donor specificity. 1. Diacylglycerol acyltransferase was resolved from rat liver microsomes and separated from glycerolphosphate acyltransferase and 1-acylglycerolphosphate acyltransferase. The separation was achieved by sucrose-density-gradient centrifugation of the enzyme preparation which was obtained by molecular-sieve chromatography of microsomes solubilized with a nonionic detergent, Triton X-100. 2. Although diacylglycerol acyltransferase and 1-acylglycerolphosphorylcholine acyltransferase were not separated from each other, the two acyltransferases were distinguishable with respect to heat stability and sensitivity to sulfhydryl-binding reagents. 3. Studies with the diacylglycerol acyltransferase preparation obtained have shown that this enzyme possesses a broad acyl-donor specificity, utilizing saturated, monoenoic, dienoic and tetraenoic fatty acyl-CoA thioesters efficiently. 4. A simplified assay method for diacylglycerol acyltransferase is described.


Characterization of a protein factor stimulating RNA synthesis by DNA-dependent RNA polymerase II from plant cell cultures. During purification of DNA-dependent RNA polymerase II (or B) from cell cultures of parsley a protein fraction was separated by phosphocellulose chromatography which enhanced RNA synthesis in the presence of native homologous DNA. This 'stimulatory factor' was characterized in respect to some effects on the reaction catalyzed by RNA polymerase II. In the presence of the factor the metal ion requirements as well as the ionic strength for optimal RNA synthesis were markedly changed; addition of the factor to RNA polymerase II purified by cellulose chromatography restored those enzyme properties which had apparently changed upon this purification step. The chain length of the RNA product synthesized is favouring the view that the factor acts mainly by stabilizing the elongation step during transcription. The stimulatory factor was further purified by several steps of column chromatography. As derived from the results of gel electrophoresis under denaturing conditions the factor consists of several small polypeptides. Those of Mr = 26000, 25000 and 14000 apparently have counterparts among the smaller subunits of highly purified RNA polymerase II from parsley cells. Another polypeptide of the factor, with Mr = 30000, was only found in those preparations of RNA polymerase II which had not been subjected to phosphocellulose chromatography.


An analysis of the bovine genome by density gradient centrifugation: fractionation in Cs2SO4/3,6-bis(acetatomercurimethyl)dioxane density gradient. The fractionation of calf thymus DNA by centrifugation in density gradients of Cs2SO4/BAMD, where BAMD = 3,6-bis(acetatomercurimethyl)dioxane, is described. A large-scale separation of (dG+dC)-rich DNA fractions has been obtained, allowing the relative amounts of minor and satellite components in the bovine genome to be precisely assessed.


Investigation into the occurrence and structure of lectin receptors on human and bovine erythrocytes milk fat globule and lymphocyte plasma-membrane glycoproteins. The reduced disaccharide beta-D-galactosyl(1-3)-N-acetyl-D-galactosaminitol was released, after alkaline borohydride and neuraminidase treatment, from human and bovine erythrocyte membrane and fat globule membrane glycoproteins as well as from human and bovine lymphocyte plasma membranes. This disaccharide was found to be substituted to different extents by sialic acid in the various fractions. beta-D-Galactosyl(1-3)-N-acetyl-D-galactosamine is the immunodominant disaccharide of the Thomsen-Friedenreich antigen (TF) and was detected serologically using specific lectins and antibody-containing sera. Bovine fat globule membrane glycoproteins were the only source of Tn antigen. The Tn antigen was detected by anti-Tn-containing sera and by the lectins from Salvia sclarea and Helix pomatiea as well as gas chromatographic detection of N-acetylgalactosaminitol after alkaline borohydride treatment of the native glycoproteins. Human milk fat globule membrane glycoproteins showed the presence of blood group A substance by reaction with rabbit anti-A serum.


Regulation of ATP pools, rRNA and DNA synthesis in 3T3 cells in response to serum or hypoxanthine. The serum-induced transition of 3T3 fibroblasts from resting to growing state is characterized by a marked increase in cellular ATP content, the maximal level of which is reached at the onset of DNA replication. This increase in cellular ATP during the G 1 period of the cell cycle is correlated with about 3-fold stimulation of transcription of rRNA measured in permeabilized cell in vitro. Addition of hypoxanthine to serum-depleted quiescent 3T3 cells gives rise to an increase in both the ATP pool and the rate of rRNA synthesis. The expansion of cellular ATP pools after growth induction by serum seems to be a prerequisite for initiation of DNA synthesis since inhibition of purine de novo biosynthesis by azaserine inhibits both ATP pool expansion and DNA replication. This effect of azaserine can be abolished by addition of hypoxanthine to the culture medium. It is concluded that (a) the increase of the rate of rRNA synthesis in 3T3 cells in response to growth factors or serum is controlled by the cellular purine nucleoside triphosphate concentration and (b) an increased ATP level is necessary for initiation of DNA synthesis but is not sufficient to trigger the events that lead to DNA replication.


Snake venom toxins. The amino-acid sequence of a short-neurotoxin homologue from Dendroaspis polylepis polylepis (black mamba) venom. The third most abundant component of black mamba venom, named FS2, was sequenced with the aid of sequenator studies and peptides derived by tryptic and chymotryptic digestion. Cyanogen bromide digests provided extra information to support the proposed structure. This protein is a homologue of the short neurotoxins of snake venom, but is much less toxic. Its structure is quite different from both neurotoxins and the other mamba proteins, called angusticeps types (neurotoxin homologues). Comparison of the known angusticeps-type toxins from mamba venom with mamba neurotoxins and each other leads to proposals that these proteins of low toxicity are inventions of the group of mambas and that three different, as yet unknown, functions will be associated with the three subgroups that are discernable.


Fluorescence urinary cytology in bladder cancer. 300 patients have been studied by means of a fluorescence exfoliative urinary cytology procedure based on the fluorochromatic properties and the affinity of acridine orange for the nucleic acids. The patients were divided inot two groups: in the first group including 238 cases we tried to establish the correlation between the urinary cytological grade and the histological grade of malignancy on biopsy; the rate of accuracy was approximately 77% for low-grade and approximately 88% for the high-grade tumours. In the second group including 62 cases we studied the value of cytology in predicting recurrences; 38 and 66.6% of the cases with grades IV and V, respectively, developed recurrences thus confirming the necessity of cytologic controls in patients under conservative treatment. The overall rate of accurate cytological diagnosis with this staining method has reached 90%.


Pressure-controlled nephrostography.

Pressure-controlled nephrostography. Nephrostomy tubes are often left in the kidney after renal operations. Radiographic studies with contrast medium via the tube post-operatively give anatomical information but little or sometimes even misleading information concerning the dynamics of the upper urinary tract. A pressure/flow-controlled nephrostogram allows not only the passage of medium to be watched but the significance of any hold-up or narrowing to be assessed in dynamic terms. In this way small degrees of obstruction can be identified. There are many situations in which this information is of considerable clinical value.


Results of the clinical use of a 'dry' kidney's hypothermia. This report describes the operative treatment of staghorn renal stones under ischaemia and hypothermia. The renal artery is blocked by digital pressure and the vascular pedicule is clamped. The kidney is cooled to an optimal level as established by the author (between 20 and 25 degrees C) by means of his own device for local hypothermia. Late results observed over a period of 0.5--5 years in 30 out of 40 patients showed no renal stone relapse and 3 (10%) 'false' relapses. In 25 cases (83.3%) the function of the kidney improved and in 8 out of 10 cases (80%) the arterial blood pressure returned to normal.


Pelvi-ureteric obstruction due to renal pelvis cyst. Intramural cysts of the renal pelvis are a separate clinical entity and must not be mistaken for neoplasms. Simple enucleation can result in complete restoration of renal function previously impaired by pelvi-ureteric obstruction.


Insemination of aspired sperm from an alloplastic reservoir: further results in bulls. Following encouraging results in rats, a similar cup-shaped silicone prosthesis of 1 ml volume was implanted 8 times upon the cauda of the epididymis in bulls. Aspirations from this prosthesis showed 10-70% motile spermatozoa up to 14 days after surgery. Aspired spermatozoa were deep-frozen in pellet form for 6 weeks. Artificial insemination in 8 cows under field conditions resulted in pregnancies in 4 of them. Clinical application for patients with aplasia or lengthy stenosis of the vas is under way.


Autoradiographic studies on DNA synthesis in renal carcinoma after preoperative radiation. In order to study, autoradiographically, DNA synthesis in tumors, kidneys containing renal carcinomas were for the first time perfused with normothermic oxygenated blood with an addition of radioactively labelled thymidine. Tumor cells preserve the ability of synthesizing DNA in spite of an unavoidable postoperative ischemia. In most cases the incorporation of 3H-TdR was inhibited significantly after preoperative irradiation with a total dose of 1,600 rad applicated 48 h before operation.


Effect of beta-adrenergic blockade on blood pressure variation in patients with moderate hypertension. The effect of beta-adrenergic blockade on blood pressure variation was studied in ten patients with moderate hypertension. Supine systolic and diastolic blood pressures were measured every 5 min during six hours sessions, using an ultrasonic method. Systolic and diastolic variation in each six hour session was defined as the standard deviation of the mean of systolic and diastolic readings made in that period. After 3 weeks of single-blind placebo, a 12 week double-blind randomized crossover study was initiated with placebo (6 weeks) and atenolol (100 mg b.i.d. for 3 weeks and 200 mg b.i.d. for 3 weeks). Systolic and diastolic blood pressure and heart rate decreased significantly (p less than 0.01) during atenolol treatment. Diastolic variation did not change significantly, whereas systolic variation decreased slightly but significantly (p less than 0.05) when expressed in absolute values, but not when expressed as a percentage of systolic blood pressure. It is concluded that beta-adrenergic blockade decreases blood pressure and heart rate without causing significant changes in spontaneous systolic or diastolic variation.


Distribution and elimination of digoxin in infants. The distribution and elimination of intravenous digoxin were investigated in seven neonates and infants with heart failure. Serum digoxin concentrations during a 24 h period were determined by radioimmunoassay, using 125I as tracer. The serum values declined biexponentially after the injection and could be fitted to a two-compartment open model by non-linear least-squares regression. The calculated mean half-lives of the distribution (alpha) phase in neonates and infants were 37 and 28 min, respectively. The mean half-life of the elimination (beta) phase in neonates was 44 h, as compared to 19 h in infants. The mean volume of the central compartment and the mean volume of distribution at steady-state were calculated to be 1.3 and 9.91/kg, respectively; no significant differences between neonates and infants were found. The relation between these volumes indicates that digoxin is extensively distributed in tissues. The steady-state distribution volumes of digoxin in neonates and infants exceed those reported in adults. The larger volume of distribution might explain in part why infants with cardiac insufficiency require larger doses of digoxin than adults (on a mg/kg body weight basis) to obtain the same serum concentrations. Elimination of digoxin from the body was slower in neonates than in infants.


Diazepam actions and plasma concentrations following ethanol ingestion. In eight normal volunteers, the combination of ethanol (0.5 g/kg) and diazepam (10 mg) administered orally produced a greater decrease in motor performance on a pursuit rotor than diazepam alone. The pharmacologic effect of diazepam was enhanced by 73% and this potentiation was associated with significantly greater diazepam concentrations (p less than 0.01) than after diazepam alone. The failure to observe any increase in the concentrations of the principal metabolite, N-desmethyl diazepam, during the period of enhanced pharmacologic effect precludes any change in the demethylating metabolic process as being responsible. The data suggest (0.10 greater than p greater than 0.05) a trend to a smaller volume of distribution of diazepam when ethanol is administered prior to diazepam ingestion. The subjects showed acute tolerance to  the effects of diazepam. Lower plasma concentrations on the ascending side of the plasma diazepam concentration versus time profile were linked with the same pharmacologic responses associated with a greater drug concentration on the descending portion, of the same curve.


A contribution to a new test method for dandruff-inhibiting and "keratolytic" action of drugs. Free cholesterol in lipids from the scalp and hair is predominantly a constituent of epidermal lipids. Therefore, a reduction in cholesterol content induced by a drug indicates a reduction in cell turnover in the epidermis. As, according to the literature, increased cell turnover in the epidermis results in formation of dandruff, a reduction in the proportion of cholesterol should indicate inhibition of the formation of dandruff. Conversely, an increase in free cholesterol should generally indicate a "keratolytic" effect. So unequivocal an interpretation has not so far been possible in persons with dandruff, as it was not known whether free cholesterol was increased or decreased. In addition, this interpretation was not possible after use of antimicrobial substances, as in vitro investigations had failed to exclude microbial esterification of cholesterol on the scalp. The present investigation has shown that correlation of free cholesterol level with cell turnover is permissible in patients with dandruff, even if antimicrobial drugs are being tested.


A rotating iterative procedure (RIP) for estimating hybrid constants in multi-compartment analysis on desk computers. The rotating iterative procedure (RIP) is a programming concept for non-linear least squares fitting of multiexponential equations to experimental data in pharmacokinetics. The method is economical in its use of program and active register capacity and can be employed in  modern electronic desk-top computers. The algorithms necessary for obtaining primary estimates of various logarithmic components and their subsequent correction are presented, with as little higher mathematics as appeared permissible. The procedure is described in the sequence that would actually be followed in a pharmacokinetic analysis, and an example is included, as well as a skeleton version of a program written in BASIC. Some instructions for obtaining overall statistical parameters are given.


Inhibition of growth in young mice treated with d,1-methadone. Neonatal mice were treated with d,1-methadone, 1-alpha-acetylmethadol (LAAM) or the narcotic antagonists, naloxone, nalorphine or levallorphan. Litter mates were injected with normal saline solution and handled in the same way. Treatment began on the second postpartum day and continued daily or on alternate days for up to 6 weeks. Injection of methadone in dosages of 2 mg/kg to mg/kg inhibited weight gain in a log dose-related fashion. LAAM, 1 mg/kg or 2 mg/kg also retarded weight gain. Mice gained weight normally when naloxone, 10 mg/kg was injected with methadone, 2 mg/kg. Furthermore the daily injection of d-methadone, 4 mg/kg, did not inhibit weight gain nor did any of the narcotic antagonists. There findings indicate that growth inhibition induced by methadone is a stereospecific, opioid effect.


The effects of zinc sulphate on vagal-induced mast cell changes and ulcers in the rat stomach. The effects of zinc sulphate pretreatment on the formation of gastric ulcers, changes in intragastric pressure and changes in the gastric mucosal mast cell count induced by electrical vagal stimulation were studied in anaesthetized rats. Vagal stimulation produced a high gastric glandular ulcer incidence and ulcer index, increased the intragastric pressure, and reduced the number of granulated mast cells in the gastric mucosa and submucosa. Pretreatment with zinc sulphate (22, 44 ot 88 mg/kg), injected i.p. 48 h beforehand, reversed the changes in these parameters in a dose-related manner. These observations suggest that the inhibitory effects of zinc sulphate on mucosal mast cell degranulation may account for its ability to antagonise vagal-induced gastric glandular ulceration. The mechanisms involved in the aetiology of this type of gastric ulcer are discussed in the light of these results.


Propranolol in DOCA hypertensive rats: development of hypertension inhibited and pressor responsiveness enhanced. D,L-Propranolol given in single doses by gavage or s.c. injection to awake rats, always slowed the heart without affecting blood pressure. Doses of 0.2 mg/100 g injected twice daily lowered systolic pressure after 3 days in DOCA hypertensive but not in normotensive or spontaneously hypertensive rats. When chronic treatment with propranolol preceded the induction of DOCA hypertension, the pressure elevation attained 14 weeks later was less in treated than in untreated rats. Pressor responses to injected norepinephrine and to posterior hypothalamic stimulation were significantly larger in DOCA hypertensive rats that had been treated chronically with propranolol than in those that had not. These results suggest that propranolol's antihypertensive effects are unimpressive because they are simultaneously opposed by an enhanced cardiovascular responsiveness to pressor stimuli.


Differential distribution of type A and B monoamine oxidase in neuronal tissues. Various neuronal tissues of the albino rabbit were assayed for type A and type B monoamine oxidase, using  norepinephrine and 2-phenylethylamine as substrates, respectively. There was an apparent positive correlation between the sympathetic character of peripheral nerves and the presence of type A monoamine oxidase activity. Type A enzyme activity was 15 fold higher in the superior cervical ganglion than in the vagus nerve. Type B activity was more uniformly distributed.


Modification by indomethacin of the blood pressure lowering effect of pindolol and propranolol in conscious rabbits. In conscious rabbits, the intravenous administration of pindolol (0.125 mg/kg) and propranolol (1 mg/kg) induced a highly significant (p less than 0.001) decrease of mean arterial blood pressure and with propranolol, a significant (p less than 0.01) bradycardia. In the same model the intravenous administrtion of saline (1 ml/kg) and of indomethacin (1 mg/kg) did not affect mean arterial blood pressure or heart rate (p greater than 0.3). Pretreatment of the animals with indomethacin (1 mg/kg) abolished the effect of both beta-blockers on mean arterial blood pressure (p greater than 0.05) and had no significant effect on heart rate.


Extracellular free calcium and potassium during paroxsmal activity in the cerebral cortex of the cat. Extracellular calcium and potassium activities (aCa and aK) as well as neuronal activity were simultaneously recorded with ion-sensitive electrodes in the somatosensory cortex of cats. Baseline aCa was 1.2-1.5 mM/l, baseline aK 2.7-3.2 mM/l. Transient decreases in aCa and simultaneous increases in aK were evoked by repetitive stimulation of the contralateral forepaw, the nucleus ventroposterolateralis thalami and the cortical surface. Considerable decreases in aCa (by up to 0.7 mM/l) were found during seizure activity. A fall in aCa preceded the onset of paroxysmal discharges and the rise in aK after injection of pentylene tetrazol. The decrease in aCa led also the rise in aK during cyclical spike driving in a penicillin focus. It is concluded that alterations of Ca++ dependent mechanisms participate in the generation of epileptic activity.


Tetanus toxin induced actions on spinal Renshaw cells and Ia-inhibitory interneurones during development of local tetanus in the cat. In anaesthetized cats the activities of Renshaw cells (RCs) and Ia-inhibitory interneurones (IaINs) were recorded during the accumulation of tetanus toxin in the spinal cord following injection into the gastrocnemius muscle. The early response of the RCs increased during the period of development of local tetanus. With some cells there was a subsequent decrease in the early response in later periods of the observation time (16-44 hrs after intramuscular injection). The effects on the spontaneous activity of the RCs were in good correspondence to those on the early response. The hyperactivity of the RCs is proposed to be mediated mainly via disinhibited cholinergic gamma-motoneurones using muscarinic postsynaptic receptors. The "pause" which follows the early response and the recurrent inhibition of IaINs was not reduced during the development of local tetanus. These results indicate that the central action of tetanus toxin in local tetanus does not consist of a general loss of postsynaptic inhibition. It is suggested that tetanus toxin acts mainly on synaptic elements of the alpha- and gamma-motoneurones or on presynaptic nerve terminals in their vicinity. In later periods of disturbing influence on the cholinergic transmission at Renshaw cells seems to occur.


The depth distribution of optimal stimulus orientations for neurones in cat area 17. Neurones recording during penetrations through cat area 17 as near parallel to the radial fibre bundles as possible have been quantitatively tested as to their optimal orientation. Optimal orientation within any one penetration was similar though considerable variability was observed. Histological reconstruction and other considerations showed that this variability could not be attributed to poor penetration angle or limitations of the microelectrode technique. These results confirm that neurones with similar optimal orientations are found in all cortical layers at one cortical locus, but it is difficult to reconcile the variability observed with a mosaic-like distribution of orientation across the cortical surface. The findings were consistent, however, with the assumption of a continuous distribution of orientation sensitivity across the cortical surface with considerable superimposed scatter.