Factors influencing the percutaneous absorption of drugs. The skin is the most readily accessible organ of the human body; only a fraction of a millimeter separates its surface from the underlying capillary network. Yet, skin protects superbly against damage by micro- and macro-molecular entities, as well as against uncontrolled loss of vital biological substances, by virtue of its astonishingly low permeability to such substances. We have reexamined and attempted to reconcile the barrier characteristics of skin in terms not only of its composition and microstructure, but also of present understanding of membrane permeability and permselectivity. The principal barrier to percutaneous transport is localized within the stratum corneum. We have developed a mathematical model of this tissue as a two-phase protein-lipid heterogeneous membrane, which correlates the permeability of the membrane to a specific penetrant with the water solubility of the penetrant and with its lipid-protein partition coefficient. We have also found that a simplistic model of the sorption process, which invokes the coexistence of dissolved and mobile sorbed molecules in equilibrium with site-bound and immobile molecules within the membrane, accurately correlates experimental sorption data and transient transport measurements. The interstitial lipid phase of the stratum corneum is the cause of the exceedingly low, apparent diffusivity of drugs (e.g. scopolamine) and, in this regard, acts as the principal permeation barrier, whereas the drug sorbed by the stratum corneum is localized predominantly within the protein phase of the tissue. We have also found that the effects of the permeation adjuvant, dimethyl sulfoxide, on skin permeability are entirely consistent with accepted sorption-diffusion models of membrane transport, when changes in penetrant activity with changes in solvent composition and tissue microstructure induced by osmotic shock are properly allowed for.


Gentamycin serum levels in a patient with severe skin damage. Pseudomonas aeruginosa grew in blood cultures taken from a 30-year-old woman with a 45% burn of second and third degree. Because of wound infection, skin grafting was unsuccessful and the wounds were left uncovered and treated topically with Eusol and saline solution. During this period 7 mg/kg gentamycin was administered to the patient daily; the blood level of the antibiotic was 3 microgram/ml, rather than the expected 8--12 microgram/ml in a patient without burns. On the eighth day, 40% of the administered dose was recoverable in the urine. With partial covering of the wounds, a dose of 5 mg/kg gentamycin daily gave blood levels of 6.5 microgram/ml. When most of the burn wounds were covered, a dose of 5 mg/kg gentamycin daily gave a blood level of 12 microgram/ml. Kidney function remained normal throughout the whole period. The possibility that gentamycin was eliminated through the burn wounds is suggested.


Exploratory skin penetration findings relating to the use of lead acetate hair dyes. Hair as a test tissue for monitoring uptake of systemic lead. Two experiments were conducted. In the first, 9 adult male subjects applied a marketed hair dye containing 2% lead acetate according to prescribed directions daily for a period of 90 days. Scalp, axillary and pubic hair were monitored for lead content before and at the end of the test period. Scalp hair analyses were used to confirm application of the hair dye; axillary and pubic hair were analyzed as biologic indicators of systemic lead absorption, i.e., metabolic incorporation of lead in hair growing at sites different from the dyed site. The axillary and pubic hair lead levels ranged from less than 6 to 41 ppm at the start and rose to 27 to 466 ppm at the conclusion of the experiment. Using 80 ppm hair lead as a measure of significant systemic absorption, 7 of 9 subjects showed this effect according to uptake by axillary hair and 4 of 9 according to pubic hair uptake. In the second experiment, blood and hair lead levels and blood erythroporphyrin were measured in 11 children from a pica clinic. Blood lead and hair lead levels were significantly correlated, i.e., r = +0.84. A regression formula was constructed relating these two parameters and blood lead values were predicted for the data of experiment 1, using observed hair lead values. The technique has important limitations; nevertheless, within these limitations, 1 of 9 subjects might be expected to have sustained an elevated blood lead level, i.e., in excess of 50 microgram/100 ml. It therefore appears that in the use of lead acetate hair dyes, some lead is absorbed systemically from the scalp.


The finite dose technique as a valid in vitro model for the study of percutaneous absorption in man. An in vitro model of percutaneous absorption has been developed which permits close stimulation of conditions commonly associated with topical drug use in living man. Quantitative comparison of the absorption of selected compounds in the model and in living man was made to test the validity of the model. Excellent agreement has been found between the two sets of data, both with respect to the total amount absorbed and the kinetics of absorption.


Quantitative determination of percutaneous absorption of radiolabeled drugs in vitro and in vivo by human skin. We have measured concentrations of about 30 drugs in the living layers of the skin under conditions which provide data which are applicable in therapeutic treatment. Since the skin is a thin organ and small amounts of drug represent high target concentrations, it is necessary to select a sensitive quantitative method; observation of the kinetics of absorption using radiolabeled drugs is the method of choice. Because of possible hazards--and legal and ethical problems--absorption studies in human skin are commonly performed in vitro. Related in vivo investigations demonstrate the relevance and the limitations of the in vitro experiments. The main hindrance against penetration of drugs is by the horny layer. The barrier-function of this layer--if it is undisturbed--may be described by a multilayer model. The reciprocal function, the reservoir function, is important for the efficiency of topical treatment; it also plays a role in determining the unique pharmacokinetics of drug absorption in the skin and percutaneous resorption. If the horny layer is injured, i.e. in diseased skin, both the barrier and the reservoir functions are disturbed. In consequence, drug concentrations in the skin--and percutaneous resorption--may be greatly enhanced, and topically applied drugs may enter preferentially into diseased areas. The form of application, such as ointment, solution, etc. influences the penetration kinetics in such a specific manner that a specific vehicle for a specific drug should always be postulated. The frequently discussed hazards of side effects due to percutaneous resorption of drugs like corticosteroids are a function of the treated area rather than of its penetration capacity. Thus the indication for local or oral treatment of severe dermatoses should be considered in terms of the affected area. The relatively frequent side effects in the skin itself which originate from unnecessarily high drug concentrations and long term treatment must also be taken into account.


Factors affecting the permeability of skin. The relation between in vivo and in vitro observations. At the same temperature and with adequate circulation of blood or receptor solution beneath it the permeability of the stratum corneum of the rabbit ear to T2O or to 32P-TPP was the same in vivo as in vitro. When skin permeability was measured in vitro, the subcutaneous adipose tissue present in the full-thickness skin of the rat delayed the penetration of CR, a lipophilic substance with a low water solubility, and decreased the permeability constant by nearly 3x. The retardant solvent PEG 300 did not penetrate the stratum corneum; it formed a hydrogen-bonded complex with the cholinesterase inhibitor VX, thereby reducing the thermodynamic activity and penetration rate of this compound through the stratum corneum. The accelerant solvent DMSO removed protein components from the stratum corneum; electron microscope studies showed that the cells of stratum corneum so treated became separated from one another, and their contents became stainable in bulk with Pb++, indicating the creation of new diffusion pathways. When the temperature, clearance of penetrant from the lower surface of the stratum corneum and penetrant formulation were the same in vivo as in vitro, and the surface of the stratum corneum was saturated with the penetrant or its solution, the results of permeability measurements made in vivo were similar to those made in vitro.


Analysis of crossingover in man.

Analysis of crossingover in man. Methods for constructing maps of male and female recombination are reviewed, including reporting of raw data, construction of standard lod tables, and analysis of heterogeneity. Chiasma distributions, physical assignments, nondisjunction, and chromosomal rearrangements are considered.


The use and limitations of chiasma scoring with reference to human genetic mapping. Human chiasma data are summarized, and some preliminary new observations in fetal oocytes are presented. Male chiasma data may give reliable estimates of genetic lengths, both for individual chromosome arms and for the total autosomal complement. Female data are as yet less accurate and give information according to chromosome group only. Movement of chiasmata before they can be reliably scored is unlikely. In both sexes, chiasmata are seen to be clustered along the length of the chromosomes, which may reflect crossingover interference and a tendency for crossingover to more often take place in certain chromosome segments; there are some indications of sex differences in these preferences.


[Myocardial protective effect using membrane stabilization in ischemic heart arrest in hypothermia]. Membrane stabilization with steroid pretreatment, procaine, or both protect against postischemic left ventricular performance after one hour of topical hypothermic ischemic arrest, but do not prevent myocardial edema. Combining steroids and procaine provide no apparent added benefit, but procaine has the technical advantage of almost immediate cardioplegia.


[Myocardial potassium and H-ion loss during normothermic, ischemic heart arrest]. Arterial and venous [K+] and [H+] concentrations were determined during normothermic ischemic arrest in cat hearts intermittently perfused without resuscitation. The slight loss in [K+] was taken as evidence of a stable membrane potential. The decrease in [H+] activity appearing in the perfusate correlated well with the previously described increase in coronary resistance. This was interpreted as a sign of restricted coronary perfusion and not as evidence for reduced anaerobic metabolic activity. Thus the functional impairment of the coronary system was confirmed to be a limiting factor when resuscitating ischemically arrested hearts.


[Metabolic status of acute myocardial infarction as a function of residual blood flow with and without revascularization]. In mongrel dogs anesthetized with Nembutal, the left anterior descending coronary artery was ligated for 2 h. The residual blood flow (RBF) was correlated with tissue levels of various myocardial metabolites after 1 and 24 h and 7 days of reperfusion. ATP and the sum of adeninnucleotides showed a better recovery with an increasing RBF. Initial increased value of creatine phosphate was followed by a decrease to subnormal values, which cannot be sufficiently explained. There was an accelerated overshoot beyond normal values in glycogen levels after 7 days with increasing RBF. After 7 days there was no recovery to normal values, and below a RBF of 5 ml/100 g/min metabolic recovery was poor.


[Haemochron--a simple method of monitoring heparin level during extracorporeal circulation]. Tow forms of heparin management during cardiopulmonary bypass were compared in order to analyze the role of the heparin level in relation to postoperative blood loss. The study was divided in three groups: In group I, the control group, 3 mg/kg body weight heparin was given as an initial dose and maintained at a dose of 1.0 mg/kg every 60 min during cardiopulmonary bypass; group II received the same initial dose, but additional doses were based upon the activated clotting time measured with a Haemochron; in group III, the Haemochron time was measured at 10-min intervals to establish a base value. In group II we found a significant decrease in postoperative blood loss as well as a decrease in the amount of heparin administered during cardiopulmonary bypass. In addition, fewer transfusions were required in the immediately postoperative period. In group III, wide variations in the activated clotting time curve were observed. No patients was underheparinized, but some had markedly prolonged Haemochron times.


[Organ blood flow in graduated, controlled hypotension induced with sodium nitroprusside]. Metabolic acidosis is a characteristic feature of SNP-induced hypotension; this acidosis is of hepatic origin and is not due to underperfusion of the organ but to cyanide-induced anaerobic metabolism. For SNP doses higher than 3 mg/kg body weight, lactate is produced in the myocardium, brain, and skeletal muscles. The observed changes were reversible after hypotension of 20 min duration.


[Animal experiments of emptying and reflux response to terminolateral gastroduodenostomy]. The reflux and emptying mechanisms of the terminolateral gastroduodenostomy after two-thirds gastrectomy was examined in dogs. Intraluminal pressure in the gastric remnant and proximal duodenum as well as cineradiographic examinations showed that the anastomosis behaves like the intact stomach. The duodenal segment which regulates gastric emptying prevents reflux into the gastric remnant by means of rising pressure.


[Substrate metabolism of muscles during the early postoperative period: the effect of glucose infusions]. Muscle substrate metabolism was studied by measuring arterial deep-venous substrate concentration differences across the forearm in metabolically healthy volunteers 3 h after abdominal surgery. Despite elevation of insulin levels following glucose infusion, no effect on muscular fractional extraction of glucose and no decrease of lactate and alanine production was found, whereas muscular lipolysis was inhibited to a normal extent and ketone utilization was reduced.


[Coagulation inhibition caused by selective thrombin blockade with hirudin]. Hirudin causes a rapid inhibition of blood coagulation as shown by in vitro and in vivo experiments in the dog. The substance appears to be a rather specific antithrombin. Its inhibitory action is linearly dose related and therefore easy to control and reproduce. Side effects can be expected to be abolished after further purification of the substance.


[The effect of citrate or heparin coagulation on the dog's heart work in autotransfusion]. During massive autotransfusion in the dog, the different anticoagulation processes have an important influence on heart work and performance. This is especially marked with citrate, depending on the amount and the transfusion rate. In spite of normovolemia both parameters show a transient decrease up to 40% - 50% with ACD and up to 60% - 70% with CPD. These different reactions may be due to the corresponding composition of each stabilizer. The effect is abolished by simultaneous use of citrate and calcium, which may prove that the observed changes are caused mainly by a depletion of ionized calcium caused by the rapid transfusion. This is comparable to the well-known citrate intoxication. In contrast both cardiac parameters decrease only about 10% with heparin anticoagulation. Heparinization seems to be preferable to citrate as regards heart work and performance during massive autotransfusion. Also the two citrate stabilizers significantly differ in their effect on both cardiac parameters, the use of ACD being favoured.


[Pre and postoperative EEG monitoring as illustrated in various routine anesthesia methods]. EEG monitoring was performed on 600 patients during anesthesia or postoperatively. Typical courses were evaluated. Examples of EEG dependence on the kind of anesthesia, the age of the patient, and individual sensitivity to the dosage of the anesthetic agent are given. These results may indicate that EEG monitoring is valuable in the clinical routine and in adjusting the dosage of anesthetics to the individual cerebral situation.


[Approach to a differentiated recurrence prevention following struma surgery]. Changes of the pituitary-thyroid axis were studied in 70 patients (45 with euthyroid goiters, 25 with autonomous adenomas) preoperatively; over a 6-week postoperative interval without thyroid-hormone treatment; under T4 therapy increased stepwise and maintained for 1 year; and over a period of 12 weeks after its withdrawal. The postoperative thyrotropic function obviously depends on the preoperative condition and thereby on the quality of the remaining tissue as well as on the extent of the operation and thus the amount of remaining tissue. The frequency of a "prehypothyroid" status in the early postoperative course is high (77%) after bilateral resection for euthyroid goiter, but decreased 1 year after the operation (47%). After unilateral resection for euthyroid goiters and after bilateral and unilateral resection or enucleation for autonomous adenomas, the remaining tissue is for the most part sufficient to avoid increased pituitary stimulation. Prophylaxis of recurrent goiter with thyroid hormones could be prescribed individually on the basis of the postoperative function of the pituitary-thyroid axis.


[Patch widening technic of benign bile duct stenosis in dogs using teflon and Solco grafts]. In 30 dogs, weighing 20 to 30 kg, the common bile duct was ligated. Pre- and postoperative bilirubin, GOT, GPT and alc. phosphatase were controlled. Eight days later a longitudinal incision was made across the stenosed segment, which was then widened with a patch. 15 dogs received a Teflon patch - 15 other dogs a Solcograft pathch. After patch-widening-plasty laboratory parameters returned to normal within a few days. X-ray controls could not find any stenosis two years after Teflon-patch-plasty, while after Solcograft-patch-plasty four dogs showed a common bile duct-stenosis within the first following year. Four weeks after Teflon-patch-plasty the patch was covered with bile duct epithelium inside. After Solcograft-patch-plasty within the first postoperative year no epithelization could be observed.


[Antibiotic concentrations of the gallbladder following cystic duct stenosis. Clinical studies and animal experiments]. Serum and bile kinetics are measured after experimental cystic duct ligation in 24 rabbits and after acute stone obstruction in 24 clinical cases. Tissue, bile, and serum levels are compared. The results clearly demonstrate that pharmacologic data alone do not give sufficient indications for antibiotic therapy in biliary tract infection. Expected pathologic bacteria and their actual resistance are considered to be of great importance in the indication of antibiotic therapy.


[Improvement of the oxygen supply of the cirrhotic rat liver by selection of portacaval shunt method]. Intrahepatic disturbances of circulation following various portasystemic shunting procedures can be monitored by means of the Pt-multiwire surface electorde. The normal liver is capable of compensating for each degree of portal blood deprivation. In the presence of a thioacetamide-induced liver cirrhosis in the rat a side-to-side PCS significantly improves oxygen supply of the liver. Preserving residual portal perfusion of the liver by choice of different portasystemic shunts, the oxygen supply is slightly improved, too. This effect does not correlate with the quantity of residual liver perfusion, but is possibly due to vasocative hormonal substances, from a pancreatico-duodenal source, that regualte liver circulation.


[The effect of liver arterialization on the regeneration process of the cirrhotic rat liver]. A portocaval shunt in the normal and cirrhotic rat liver results in a considerably diminished regenerative response following a 70% hepatectomy. Increased regenerative activity of a normal liver after arterialization of the portal vein is not necessarily due to improvement of total blood supply, since a similar regenerative response in the cirrhotic liver does not occur, although regenerative activity in a cirrhotic liver is quite similar to that in a normal liver. In the presence of a TAA-induced liver cirrhosis, liver regeneration 7 days after PCS and 70% hepatectomy is not improved by additional arterialization of the portal vein.


[Long-term study of endocrine inhibition of exocrine pancreas secretion in the conscious dog]. A new model of a reversible long-term pancreatic fistula was used on an alert, unrestrained dog to test the effect of four substances of the GEP system on the exocrine pancreatic function. The results indicate that SST significantly inhibits not only the basal secretion but also the stimulated secretion of volume, bicarbonate, and trypsine. Calcitonine inhibits only the stimulated secretion whereas PGE1 inhibits only the secretin-stimulated output of trypsine. Glucagon inhibits secretin stimulation in all three parameters.


[Diagnosis of malignant processes of the colon and rectum using a new method for the demonstration of sensitized lymphocytes (PAL-test)]. Peripheral blood lymphocytes of 45 patients with colon-rectum disease and 30 healthy controls were tested in a simple rapid microagglutination test (PAL test) for cancer diagnosis. In 30 cancer patients 28 positive reactions were obtained. All healthy controls were negative. The 15 patients with benign or premalignant lesions showed 5 positive and 10 negative reactions. Results of the PAL test were about 90% accurate.


[Leukocyte migration test and determination of carcinoembryonic antigens in the postoperative follow-up care of colon and rectum carcinoma]. Preoperative and serial postoperative CEA determinations have become widely accepted tools to aid the early detection of recurrent colorectal cancer. The panel modification of the direct leukocyte migration test (LMT) has proved to be an excellent monitor in these tumor patients. In this study LMT and CEA-RIA were compared. Peripheral blood leukocytes were pulsed with a high dose (2.5 and 0.5 mg/ml) of 3 m KCl extracts of five different colorectal tumors as well as with one 3m KCL extract of normal colonic mucosa. Patients showing a pathologic migration index (less than 0.80 and greater than 1.17) of 3 or more out of five tumor extracts were considered to be "positives." With this test mode 51 of 59 (86%) patients with resectable tumors were reactive, while only 24 of 69 (41%) yielded elevated CEA values. Both LMT and CEA-RIA were positive in 12 of the 13 patients with nonresectable tumors. After curative surgery most patients' leukocyte migration and CEA values were in tne normal range. Of the nine patients with localized tumor recurrence, eight were LMT reactive and five showed elevated CEA values. Of five patients with distant metastases, four demonstrated a positive reaction in the LMT and five a rise in CEA levels. The combination of the LMT with the CEA-RIA promises to improve the detection of recurrent colorectal cancer before the appearance of clinical evidence of recurrence.


Pretherapeutic cytostatic agent sensitivity testing of breast cancer. With and without addition of cytostatic agents, incorporation of radiolabeled precursors into the nucleic acid of breast cancer cells was determined in short-term culture. The labeling index, a measure of tumor proliferation, depended largely on cytologic differentiation. Incorporation of radiolabeled precursors in moderately and low differentiated breast cancers was significantly high, whereas only in a part of these tumors was incorporation inhibited by adriamycin and cyclophosphamide. Therefore a group of drug sensitive and metabolic drug resistant tumors could be defined in vitro. Primary resistance against the tested cytostatic agents has been proved in low proliferating and high differentiated breast cancer cells.


[Permeability of the gastric mucosa for carcinogens in taurocholate-induced injury of the mucosa barrier]. The influence of taurocholate-induced damage of the gastric mucosal barrier on transmucosal movement of methyl-N-nitro-N-nitrosoguanidine (MNNG) was investigated on dogs with Heidenhain pouches. We also investigated whether or not MNNG influences the mucosal barrier. The results of 10 experiments revealed no effect of MNNG on the mucosal barrier, but a significant time-related decrease of intraluminal MNNG concentration in the presence of taurocholate.


[Animal experiments on the modification of fracture healing by growth hormone (STH)]. Human growth hormone seems to improve fracture healing. Using rat experiments, the clinical experiences of other authors were reviewed critically. Examination of metabolic parameters showed no useful results. Measurement of bone length and circumference and comparison of radiographs, scintigraphs, and histologic examinations indicated positive results with regard to the improvemnt of osseous consolidation when influenced by growth hormone.


[Osteogenetic potential of gelatin and collagen in poorly regenerating bone layers (animal experiments)]. Normal tissue defects in the tibiae of 16 sheep were filled with gelatine, collagen or a mixture of both. Comparable rates of new bone formation occurred after observation periods of 6 and 12 weeks. The difference is not statistically significant. In our experiment collagen and gelatine showed neither a positive nor a negative influence on new bone formation.


[The effect of selective proximal vagotomy on gastrin, GIP and insulin blood levels in patients with duodenal ulcer]. 1. In duodenal ulcer patients SPV results in an increase of basal and postprandial serum gastrin levels. There is no decrease of hypergastrinemia even five years after SPV. 2. After SPV there is a significant increase in basal serum GIP levels; postprandial GIP concentrations show a faster increase after food intake. 3. Serum insulin and blood glucose concentrations are not altered by SPV.


[In vitro culture system for the characterization of growth potential of cartilage transplants]. In order to find reliable criteria for determining the prognosis of transplanted cartilage, the quality of isolated rabbit chondrocytes was assayed in vitro. A culture system of semisolid medium was able to detect colony-forming units of chondrocytes. Also their proliferative and differentiating capacity could be investigated. Colony formation in vitro follows a strict dose-response relationship. An inverse relationship was observed between age of the donor and the colony incidence in vitro. Cells from neonatal cartilage could be induced to grow as fibroblastic colonies in the presence of conditioned medium from fibroblastic monolayer cultures. No effect, however, could be observed with chondrocyte-derived conditioned medium.


[Tension changes of the anterior cruciate ligament in the movement process of the knee joint]. Relative tension of the anteromedial part of the anterior cruciate ligament of five cadaver knees is measured. The ligament is taut at 80 degrees - 90 degrees flexion and loosened to a maximum at 30 degrees and 130 degrees flexion. On internal rotation it is taut at each stage of flexion, on external rotation, only at full extension and full flexion.


[Tensile strength of partially cut lateral knee ligaments following, or without plaster immobilization]. The tension strength of partially cut medial collateral ligaments of rabbits was higher after functional treatment than after casting. Therefore we conclude, that functional therapy after surgical treatment recommeneded by Burri et al. (3) has a beneficial effect on tension strength of human collateral ligaments.


[Metabolic status of hypothermically stored dog kidneys with various perfusion solutions and ischemia pretreatment]. In experiments on canine kidneys, cortical edema formation during hypothermic storage following a period of normothermic ischemia of up to 30 min duration was - according to the osmolality of the perfusion fluid - lower after flush perfusion with Sacks II solution than with Biotest-"Collins" solution or Ringer-mannitol solution, which resulted in the highest edema. The adenine nucleotide content fell corresponding to the duration of the hypothermic storage or the duration of an initial normothermic ischemia, but only small further changes were found during storage following initial normothermic damage. Moreover, with respect to the maintenance of nucleotide contents the strong hyperosmolar intracellular solutions were not superior to Ringer-mannitol solution of 330 mosmol/liter.


[Effect of adenosine and inosine on the metabolic status of preserved kidneys]. Isolated rat kidneys were preserved by continuous perfusion or retrograde oxygen persufflation in a medium of the extracellular type with and without addition of adenosine or inosine at 6 degrees C. After 4 and 24 hours of preservation the metabolic states was analysed. In the kidneys preserved by continuous perfusion, only adenosine was able to slow down the loss of nucleotides. With the retrograde oxygen persufflation the stock of high-energy phosphates could be preserved in any case, but no increase in the nucleotide content by neosynthesis was achieved by means of the addition of adenine nucleotide precursors.


[Stomach movement following selective gastric vagotomy: correlation of roentgen contrast studies and electromyography in the conscious dog]. Electrical gastric activity in the alert dog was continuously registered by bipolar steel electrodes simultaneously with contrast x-ray studies. Delayed gastric emptying in the postoperative period following selective gastric vagotomy and pyloroplasty can be attributed to specific changes of electrical activity: 1. Electrical potential units become irregular in amplitude and frequency; 2. electrical activity of antrum is no longer synchronized with the corpus; 3. appearance of high frequency, atypical electrical activity in the antrum is associated with gastric motor inactivity; 4. peristalsis and emptying are linked to the de novo appearance of action-potential bursts.


[Significance of the hemodynamics for the extent of the rejection. Comparison of immunological reactions in artery transplantation in high pressure and vein transplantation in low pressure systems in matching inbred rat strain combinations]. Systemic sensitization is induced by arterial transplants in the high pressure system and by venous transplants in the low pressure system. In aorta transplantation the severity of the rejection corresponds directly to the immunogenetic differences between donor and recipient; the efferent limb is triggered into action. For application of allogeneic veno-venous transplants this is not the case: despite systemic sensitization, even strongly allogeneic venous transplants are maintained over long periods. A threshold value is not reached unless there is presensitization with strong antigens, after which morphologically comprehensible rejection reactions, i.e. round cell infiltration, are demonstrated even in veno-venous transplants.


[The effect of vagus and sypathetic nerves on blood flow in the swine stomach]. Porcine gastric blood flow (radioactive microspheres) was studied (aortic blood pressure controlled) under five conditions: control (n = 8), electric stimulation of the splanchnic nerves (n = 8) and the vagus nerves (n = 8), truncal vagotomy (n = 8), and gastric sympathectomy (splanchnicotomy, n = 5). Highly significant increase in corpus mucosa flow after vagal stimulation or gastric sympathectomy is antagonistic to changes after splanchnic stimulation and truncal vagotomyand is often contrary to changes of the antrum mucosa. This might be an explanation fir ischemic gastric lesions (stress ulcer) after stress-induced high sympathetic tone (1, 2) and stress ulcer prophylaxis by gastric sympathectomy (3, 4).


[Energy metabolism of the intestinal wall in ileus]. In dogs, a segment of an aborrally occluded small intestine was anastomosed to the right colic flexure; thus, distal to the trapping ileocecal valve a local intestinal obstruction developed within a week in the small and large intestines, which locally stimulates the ileus situtation in man. Distrubances of the energy metabolism, as demonstrated by significant changes in the adenylic acid and phosphocreatine system, were more intensive in the mucosal layers of the small intestine than in those of the large intestine, whereas the smooth muscle layers were unaffected. The results reflect different disturbances of blood flow, energy needs, and adaptability of intestinal mucosa and musculature.


[Function of the lower esophageal sphincter in infants]. Main basal pressure and the deglutition-induced behavior of the lower esophageal sphincter (LES) in 115 infants between the ages of 6 hr and 6 mo were evaluated by continuous perfusion manometry. In comparison to the adult, higher pressures were found, especially in the first weeks and months of life. The relaxation stimulated by the deglutition reflex and the pressure increase following abdominal compression were similar to the responses observed in adults. Singificant differences between vomiting and nonvomiting infants could be determined. From these results we conclude that the vomiting often observed in early infancy results from factors other than the previously proposed hypotonia or neuromuscular underdevelopment of the LES.


[Cardia function following Billroth I and Billroth II gastrectomy (studies on the significance of duodenal passage for cardia function)]. To clarify whether the duodenum is important to the regulation of cardia function, patients with B-I and B-II resections were investigated manometrically. A test meal can stimulate the LES in patients with a B-I resection almost to the same extent as that in healthy test persons. Symptom-free patients with the distal stomach resection and gastrojejunostomy (B-II) do not show this pressure reaction. Therefore, the duodenal passage could be of importance to cardia function. In patients with a transformation operation of B-II in B-I, because of postgastrectomy symptoms a stimulation of the LES cannot be achieved either before or after the transformation operation. We cannot presently clarify the type of the cardia regulation since the IRG levels measured do not explain this phenomenon.


[Reflux and prevention of reflux in the resected stomach]. 1. After gastrectomy or vogotomy with pyloroplasty the reflux of bile acids and lysolecithin increased. 2. The highest values of reflux were observed in the retrocolic (short loop) B-II anastomosis. The different types of B-I antrectomy and the antecolic B-II with Braun's enterostomy have each the same reflux, which is significantly lower than the retrocolic B-II. Even these types of gastrectomy have 6 - 10-fold elevated reflux values compared to the controls. After vagotomy with pyloroplasty the reflux was reduced to two or three times normal. After selective proximal vagotomy without pyloroplasty no reflux was observed. 3. After an isoperistaltic jejunal transportation, the reflux was reduced, the reduction depending on the length of the transposed segment. The same result was obtained with a ROUX-en-Y-gastro-enterostomy. 4. After hemigastrectomy and isoperistaltic transposition of 25 cm of jejunum, more reflux could be observed under experimental and clinical conditions.


[Experimental model of protracted traumatic-hemorrhagic shock. I. Organ blood flow]. Experimental trauma and hemorrhage acutely reduce capillary blood flow in all organs except the heart. After reinfusion of the withdrawn blood a long-lasting increase of pulmonary bronchial blood flow and hepatic and renal blood flow is observed parallel to a rise in cardiac output. However, blood flow in the intestines, pancreas, and spleen remains significantly reduced. Particularly, renal and pulmonary bronchial blood flow is significantly higher in animals surviving for 72 hr than in animals succumbing after an average of 32 hr.


[Experimental protracted shock. II. Blood coagulation and histological changes]. Twenty mongrel dogs are subjected to a standardized traumatic hemorrhagic shock. After reinfusion of the dogs' own blood the animals are continuously observed for the 72 hr. Deterioration of general hemodynamics and activation of intravascular coagulation is more pronounced in the nonsurviving animals. Correspondingly, histologic alterations particularly of the liver and intestine are more marked in the nonsurvivors. Increase of partial thromboplastin time and long-lasting increase of the prothrombin time (Quick) appear to be early signs of a fatal prognosis.


[Blood flow in the swine stomach in hemorrhagic shock]. In nine conscious piglets, total and regional gastric blood flow was measured (8 microns radioactive microspheres) in the same animals before (control) and at the end of a 3-h hemorrhagic shock period (mean AoBP = 40 mm Hg). Gastric blood flow decreased dramatically (88.4%) during shock. This decrease was most severe in the mucosa of corpus and fundus, where the highest flow was registered during control and where stress lesions are usually found. The reduction in gastric flow was significantly greater than the reduction in cardiac output (45.1%). The disproportional reduction in gastric blood flow may be explained by the high alpha-adrenergic activity of splanchnic organs (2) and by the impediment to liver outflow (1) during hemorrhagic shock.


[Inhibition of thrombocyte aggregation in hemorrhagic shock using acetylsalicylic acid and mechanical ventilation]. Platelet aggregation in flowing venous and arterial blood during hypovolemic hypotension is followed by a previously described photoelectric method. It is shown that platelet aggregation can be inhibited by acetylsalicyclic acid (ASA) and by artificial ventilation. The inhibition of platelet aggregation by artificial ventilation is significantly more pronounced than that by ASA. That different times are needed for platelet aggregation in venous and arterial blood in dogs treated with ASA and with artificial ventilation is informative about the canine lung not only as a filter for aggregates but also as a source of aggregating substances.


[Animal experiment evaluation of myocardial protection with a magnesium-asparaginate-procaine solution]. Cardioplegic myocardial protection with magnesium asparaginate procaine (Cardioplegin) is assessed in normothermic ischemia by left ventricular function curves. Different ischemic times (20, 30, 40, and 50 min) and different doses of Cardioplegin (2, 4, and 6 ml/kg) were studied in 68 mongrel dogs. Postischemic myocardial function was depressed in all experiments. However, in the Cardioplegin groups all animals showed signs of recovery and a significant, but not dose-related, hemodynamic improvement compared to the controls.


Delta-9-tetrahydrocannabinol inhibition of suckling-induced prolactin release in the lactating rat. To study effects of delta-9-tetrahydrocannabinol (THC) on the regulation of prolactin (PRL) release, a chronic cannula was placed in the right atrium of postpartum lactating rats. Two or more days later their pups were removed for 6--8 hours. A blood sample was drawn from the mother just prior to reintroducing the pups, for determination of basal levels of plasma PRL. A second sample was drawn following 30 min of continuous suckling. THC (1.25 or 4.0 mg/Kg) or vehicle was then injected intravenously and blood samples obtained 30, 60, 120 min later. Relative to vehicle-injected controls, both doses of THC significantly reduced plasma PRL levels and disrupted all components of maternal behavior. These findings indicate that THC inhibits suckling-induced PRL release in the postpartum rat.


An improved method for the measurement of 1,25-(OH)2D3 in human plasma. Here we report a highly sensitive and convenient ligand binding assay for the determination of 1,25(OH)2D3 in small volumes of human plasma. This method involves: (1) extraction of vitamin D3 and its metabolites using methanol-methylene chloride with separation of phases by centrifugation; (2) gel chromatography and high pressure liquid chromatography for the quantitative isolation of 1,25-(OH)2D3; and (3) a sensitive ligand binding assay for 1,25-(OH)2D3 employing cytosol receptor from the intestinal mucosa of rachitic chicks. Using modified rachitogenic chick diets allows early (less than 4 wks) harvesting of active receptor for 1,25-(OH)2D3 in high yield. The method includes a rapid and effective procedure for stable and long-term storage of the active cytosol receptor. A convenient dextran-charcoal means is used for the separation of receptor bound from free 1,25-(OH)2D3 resulting in the achievement of a lower (less than 5%) background (i.e., nonspecific binding) than reported for other 1,25-(OH)2D3 assays. Analysis of this receptor shows it to be a saturable, single class of binding sites with a dissociation constant (Kd) of approximately 3.7 x 10-11. The final recovery of 1,25-(OH)2D3 following extraction and chromatography is 80 +/- 3% and triplicate determinations can be made on a 3 ml plasma sample. The ligand binding assay routinely detects less than or equal to 5pg of 1,25-(OH)2D3 per assay tube and the inter- and intraassay variation, based on repeated determinations of 1,25-(OH)2D3 in pooled normal human plasma, is less than 5%. Preliminary studies indicate that our methodology will permit measurement of plasma 1,25-(OH)2D3 levels in all normal subjects and in pathophysiologic states where 1,25-(OH)2D3 levels may be below or above normal values. 1,25-(OH)2D3 values (pg/ml +/- SEM) in human plasma obtained from both normals and patients with various untreated calcium homeostatic disorders were: normals = 33.5 +/- 1.8; end-stage chronic renal failure = 5.1 +/- 1.2; primary hypoparathyroidism = 18.3 +/- 2.8; primary hyperparathyroidism = 61.4 +/- 7.1; and hyperthyroidism with associated hypercalcemia = 42.1 +/- 8.4.


Pineal serotonin N-acetyltransferase activity and melatonin concentrations in prepubertal and adult Syrian hamsters exposed to short daily photoperiods. Pineal serotonin N-acetyltransferase activity (NAT) and melatonin concentrations were determined at various intervals in prepubertal (35 days old) and adult male hamsters (74 day old) throughout a 24 hour period with the animals kept in a light:dark cycle of 6:18 (lights on at 0600 h and off at 1200 h). In prepubertal animals, daytime pineal NAT activity of 0.20-0.28 nmoles 14C-N-acetyltryptamine/pineal/hour was maintained for 8 hours after the initiation of darkness. Peak pineal NAT activity of 0.46 +/- 0.64 nmoles 14C-N-acetyltryptamine/pineal/hour occurred 13 hours after the onset of darkness and remained significantly elevated until 0400 h (p less than 0.001). Daytime pineal melatonin concentrations of 78-194 pg/pineal gland also were maintained for 8 hours after the initiation of darkness. At 13 hours into the dark period, pineal melatonin concentrations rose to 788 +/- 150 pg/pineal gland (p less than 0.01 vs all other time points except 0230 h and 0400 h). At one hour before the onset of light both the pineal NAT activity and pineal melatonin concentrations returned to daytime values. Adult male hamsters had diurnal pineal NAT and melatonin rhythms which are indistinguishable from those found in the prepubertal animals.


Prevention of normal mouse uterine maturation by antipain and elastatinal: suppression of peroxidase activity. We had shown previously that the serine protease inhibitors, antipain and leupeptin, restrict uterine DNA snythesis and function in adult mice. The present study is an extension, focusing on the perimaturation period. The protease inhibitors, antipain and elastatinal were tested and the end points were uterine development and peroxidase activity in the uterus. Four week old mice were treated with eigher antipain (3 mg), elastatinal (5 mg) or vehicle (control) twice daily for 3 weeks. The uteri were excised, weighed and homogenized. Subcellular fractions were prepared by differential centrifugation. Each fraction was analyzed for peroxidase activity. The weights and protein content of uteri from control mice averaged greater than twice those in either antipain or elastatinal treated mice (p less than 0.001). Peroxidase activity was sharply curtailed by both inhibitors, antipain being more active than elastatinal. Mechanistically, antipain and elastatinal may act directly on the uterus either by inhibiting key enzymes or by preventing the formation of macromolecules crucial to normal function. Alternatively, the protease inhibitors may interfere with ovarian function, thereby restricting normal uterine development.


Specific binding of estrogen to nuclei from Japanese quail kidney cells. The binding properties of estrogen to Japanese quail kidney cell nuclei were evaluated by 3H-17 beta-estradiol exchange. Kidney cell nuclei from estrogenized male, as well as laying female quail, had a single class of saturable (0.1-0.2 pmol/mg DNA), high affinity (Kd = 1-2 x 10-10M) nuclear binding sites for 17 beta-estradiol. High affinity estrogen binding sites were not found in kidney cell nuclei from untreated males. Various non-radioactive estrogens (17 beta-estradiol, estrone, estriol and diethylstilbestrol) competed effectively with 3H-17 beta-estradiol for the high affinity binding sites, whereas nonestrogens (testosterone and progesterone) did not complete. It is concluded that the 3H-estradiol binding characteristics of kidney cell nuclei provides strong evidence for a nuclear estrogen receptor in the avian kidney.


Effect of the calcium antagonist nifedipine on uterine blood flow in non-treated and oestradiol-treated rats. Organ blood flow, as estimated by the radioactive labelled microsphere technique, was studied in rats before and after intracaval administration of the calcium antagonist nifedipine. Intra-uterine and arterial blood pressures were registered simultaneously. Two groups of animals were investigated, one non-treated and one treated with oestradiol. After administration of nifedipine, an increase in the blood flow to the brain, the heart and the kidneys was seen in both groups of animals. However, in the uterus, blood flow was markedly increased in non-treated, but not so in oestradiol-treated animals. The arterial blood pressure and intra-uterine pressure were almost unaffected. The results suggest that nifedipine can markedly increase blood flow to the uterus of non-oestrogen-treated rats with only minor effects on intra-uterine and arterial blood pressures.


Changes in semen quality and fertility in response to endocrine treatment of subfertile men. 786 subfertile men received hormonal treatment in order to improve their semen quality and concentration. Most of the patient's semen was characterised as idiopathic oligo or asthenozoospermia. No cases of hypothalamohypopituitary-hypogonadism were included in this study. 117 men received human chorionic gonadotropin (hCG); 47% showed improvement in semen quality mainly in motility and morphology: 10 pregnancies were recorded among 44 couples (23%). 37 received human menopausal gonadotropin (hMG) + hCG; 46% improvement in semen quality, mainly in the motility and concentration was seen: 3 pregnancies were recorded among 20 couples (15%). 60 men received clomiphene citrate; 47% showed improvement in semen quality mainly in the concentration and motility: 2 pregnancies were recorded among 33 couples (6%). 270 men received androgen, usually in small doses; 61% had improvement in semen quality, mainly in the motility and morphology: 24 pregnancies were recorded among 58 couples (41%). 262 men received pregnant mare serum (PMS; Gestyl) and testosterone; 71% had improvement in semen quality in all the parameters measured especially in motility and vitality, but only 24 pregnancies were recorded among 87 couples (28%). 40 men received treatment for improvement of potency which included androgen, yohimbine and strychnine; 60% improvement in sexual potency, 65% showed a significant improvement in semen quality: 4 pregnancies were recorded among 15 couples (27%). The parameters for improvement of sperm quality were motility, concentration, morphology and vitality. Improvement in semen quality was not necessarily correlated with impregnation of the wives.


Limitations of a single extra-amniotic injection of prostaglandins in viscous gel to induce midtrimester abortion. A dose-response study using PGE2 in a viscous gel has been undertaken for induction of midtrimester abortion. A direct relationship was found between the time to abortion and the dose administered. However, even using PGE2 3.5 mg induced uterine activity was noticed to subside in a significant number of women after approximately 6 h. For routine management it is suggested that PGE2 3.5 mg be injected and followed by repeat doses 6 h later with removal of the injecting catheter on each occasion.


Characterization of relaxin radioimmunoassay using Bolton-Hunter reagent. First results in plasma during pregnancy, and in placenta, corpora lutea and ovarian cysts in woman. Application of a porcine relaxin radioimmunoassay system using Bolton and Hunter reagent was characterized in different biological fluids. In pregnant woman, plasma reveals concentrations from undetectable values to 1,800 pg/ml. Maximal concentrations are found between the 8th and the 13th weeks of pregnancy. These peak values are significantly different from those at other stages of pregnancy. Appreciable relaxin concentrations are detected in gestational corpus luteum extract, and in corpora lutea cyst fluid of pregnant and nonpregnant women. No relaxin was detected in a cyclus corpus luteum extract, in a placental extract, or in an ovarian serous cyst. The presence of immunoreactive relaxin in the nonpregnant woman is reported.


Short-term variations in urinary estriol and renal function. Possible effects of extraneous conditions. Variation in urinary excretion of estriol was found to be related to physical activity and climate conditions. Estriol content of sweat was studied but was found not to be of an order to explain the variation observed. Estriol clearance rate was significantly reduced even by moderate physical activity. Creatinine clearance was not affected to the same extent. Different explanations to the findings are discussed. The need for strictly standardized conditions during urine sampling for estriol assays in risk pregnancies is stressed.


Alcohol and drug education: models and outcomes. Knowledge-attitude-behavior and values-based models are analyzed with regard to their application to development and evaluation of drug education programs; theoretical problems of these models are identified. The experimental evidence regarding the application of these models to drug education is reviewed. Recommendations are made concerning theoretical, programming, and research implications for drug education and for health education in general.


The potential of grounded theory for health education research: linking theory and practice. This paper offers a critique of present research methods used in the literature drawn upon by health education practitioners, students, and teachers. Weaknesses of deductive methods and of theory which is highly general are noted in terms of their implications for the advancement of health education theory and practice, and in terms of their consistency with traditional principles of practice. The grounded theory method--an inductive approach usually used with participant observation and interview data--is described, and the major arguments for its value are presented. In particular, the empirical generation of middle-range theory can provide a strong link between more general theory and situations faced by practitioners, and definitions of problems are not prematurely closed to reinterpretation from other perspectives. Several recommendations are given for changing the research orientation of health education.


Cutting back after a heart attack: an overview. Increasingly, health workers are concerned with the alteration of complex and deeply embedded behaviors; essential to these tasks is an understanding of the other's situation as he or she views it. This study took the perspective of the patient, inductively generating a conceptual formulation to explain and understand life after a heart attack. The basic problem of minimizing losses under conditions of uncertainty and unknown parameters of action is confronted. Resolution is achieved through "cutting back," which has three major stages: (1) immobilization, characterized by explaining and estimating the damage; (2) resumption, in which patients figure the complex calculus of the new situation to determine what they must cut back, what they should cut back, and what they will and will not cut back; and (3) new normal, when the major work is that of adjusting to the permanent changes wrought by the heart attack experience which affect identity. Exploratory diagnosis of complex health education problems through a "grounded theory" approach is demonstrated by the study.


A procedure for using peak expiratory flow rate data to increase the predictability of asthma episodes. An examinaton was conducted of the relationship between Peak Expiratory Flow Rate (PEFR) measurements obtained in the homes of two boys with asthma and the predictability of asthma episodes. An approach was developed for assessing the predictive utility of PEFR data. Results indicated approximately three-fold increases in the predictability of asthma episodes for the two experimental subjects. Potential applications of these results to the management of asthma are discussed.


Ca2+ binding, ATP-dependent Ca2+ transport, and total tissue Ca2+ in embryonic and adult avian dystrophic pectoralis. Avian muscular dystrophy is an autosomal recessive genetic disease characterized by early hypertrophy and loss of function of pectoralis major. The disease is progressive, ultimately resulting in atrophy and heavy lipid deposition. Previous investigators have noted a decrease in the ability of the dystrophic sarcoplasmic reticulum to concentrate Ca2+. More recently, other investigators have shown an abnormal calcium uptake in avian dystrophic sarcoplasmic reticulum. They indicated, using freeze-fracture techniques, that a 90 A particle of the vesicle membrane exhibited a decreased population and suggested that they might be the ATPase involved in calcium transport. Our studies confirm earlier observations of a decreased rate of Ca2+ uptake and Ca2+ binding capacity of dystrophic fragmented sarcoplasmic reticulum vesicles which are isolated from both embryonic and adult pectoralis. These observations correlate in turn with a 75% drop in the Ca:ATP transport efficiency of the dystrophic sarcoplasmic reticulum determined by measuring the rate of 32Pi liberation from gamma-ATP32 during active calcium transport by the isolated sarcoplasmic reticulum SR. In addition, we have found a quantitative deficiency in a 65,000 dalton component of the dystrophic fragmented SR at the time of myoblast fusion by measuring 35S-Methionine incorporation into the SR, coupled to high resolution polyacrylamide gel electrophoresis and radioautography. Analysis of total tissue calcium by atomic absorption spectroscopy revealed a decrease in the total calcium content of dystrophic muscle.


Metabolic stimulation of polymorphonuclear leucocytes: effects of tetravalent and divalent concanavalin A. Polymorphonuclear leucocytes (PMNL) undergo a marked activation of their oxidative metabolism upon interaction with surface-reactive soluble stimuli as well as with phagocytosable objects. To get some insight into the mechanism of this stimulation, we have compared the stimulatory activity of the tetravalent lectin concanavalin A (Con A) with that of the divalent derivative succinyl-Con A (S-Con A). Both lectins bind to the PMNL surface to the same extent. S-Con A, however, is much less efficient in stimulating the PMNL metabolism. When S-Con A-treated PMNL are further reacted with antiserum to Con A, a potentiation of the metabolic stimulation is observed. Normal serum or addition to PMNL of antiserum to Con A in the absence of lectin has no effect. Furthermore, if S-Con A is displaced from its receptors on the cell membrane with alpha-methyl mannopyranoside, the addition of antiserum fails to cause a respiratory stimulation. These results suggest that the initial triggering of the metabolic stimulation of PMNL is in part accomplished through cross-linkage of membrane constituents.


Effects of conditioning polarization on the membrane ionic currents in rat myometrium. Membrane ionic currents were measured in pregnant rat uterine smooth muscle under voltage clamp conditions by utilizing the double sucrose gap method, and the effects of conditioning pre-pulses on these currents were investigated. With depolarizing pulses, the early inward current was followed by a late outward current. Cobalt (1 mM) abolished the inward current and did not affect the late outward current per se, but produced changes in the current pattern, suggesting that the inward current overlaps with the initial part of the late outward current. After correction for this overlap, the inward current reached is maximum at about +10 mV and its reversal potential was estimated to be +62 mV. Tetraethylammonium (TEA) suppressed the outward currents and increased the apparent inward current. The increase in the inward current by TEA thus could be due to a suppression of the outward current. The reversal potential for the outward current was estimated to be -87 mV. Conditioning depolarization and hyperpolarization both produced a decrease in the inward current. Complete depolarization block occurred at membrane potential of -20 mV. Conditioning hyperpolarization experiments in the presence of cobalt and/or TEA revealed that the decrease in the inward current caused by conditioning hyperpolarization was a result of an increase in the outward current overlaping with the inward current. It appears that a part of the potassium channel population is inactivated at the resting membrane potential and that this inactivation is removed by hyperpolarization.


Radiology of multiloculated fibrous dysplasia of the jaws. Three cases of multiloculated lesion of the jaw (two in the mandible and one in the maxillar) closely mimicking ameloblastoma are described. Histology showed all three to be fibrous dysplasia. Against a diagnosis of ameloblastoma were (1) the relative fuzziness of the margins of the loculi and septae; (2) the mineralization of the matrix which gave a ground-glass background instead of the distinct radiolucency seen in ameloblastoma; and (3) the non-resorption of the dental root apices within the lesion.


Research in the family physician's office. Family medicine as a specialty has now "come of age." To maintain its new status, the specialty must be able to survive the vigorous assessment that is given other specialties by the public, the profession, and the academic community. One way of achieving this is for the family physician to do research of excellent quality and quantity. Traditionally, medical research has been done by secondary and tertiary care specialists and little has been done on the primary care needs of the black patient. The research done is of limited value for the family physician's daily work, a reason why family practitioners must do their own research. A research methodology has been described which is readily applicable to the family physician's office. It is an extension of good record keeping and includes Problem-Oriented Medical Records, an Age-Sex Register, a Daily Worksheet or Encounter Form, and a Morbidity Index, incorporating the "Pri-Care" (ICHPPC) code. The system is simple to use and requires only a small increase in administrative time. Every family physician is encouraged to consider its use.


Antibiotic prophylaxis in high-risk obstetrics. Unregistered patients, who subsequently had cesarian section for obstetric indications, were placed on prophylactic chloramphenicol in doses of 2-6 gm a day. These were matched with an equal number of randomly selected, similarly unbooked patients not receiving prophylactic antibiotics. These groups were given a fever work-up when sepsis manifested even in those previously on antibiotic therapy.Results showed little or no significant difference in the two groups when length of hospitalization and cost of care were compared. During the period of the study, a sample of booked patients, who subsequently had cesarian section, were also compared. Highly significant differences were noted. In Nigeria, a more rational approach to this group of significantly high-risk patients is advocated. A review of current practices in obstetrics is discussed.


Lead poisoning in children.

Lead poisoning in children. In this study of the phenomenon of lead poisoning in children, the various approaches that several cities have employed to combat the problem are discussed. Several suggestions for dealing with the situation are proposed. These include educational programs, followup reports, legislation, and research.


Frequency analysis of the EEG in children with sickle cell disease. An automated technique for EEG frequency analysis was employed in the study of nine children with sickle cell disease. Quotients, Q(1) (delta+theta/alpha+beta) and Q(2) (theta/alpha+8), were calculated from the computed power in each frequency range. Recordings from occipital-parietal and temporal-frontal areas resulted in a higher Q(1) for sickle cell disease patients than for reported normals (p<.002 and p<.05 respectively). Q(2) value from the occipital-parietal sites were also higher for the sickle cell group (p<.05).The technique reported here lends itself to serial studies in appropriate patient groups and suggests the possibility of an organic basis for some of the results found.


Test method for the absence of active clotting factors in dried human blood coagulation factor IX complex. Adverse effects possibly due to the active clotting factors are sometimes reported upon administration of some preparations of Factor IX complex having conformed to the specifications in the Japanese Minimum Requirements for Biological Products. The author, therefore, proposed the revision of the test method for the absence of active clotting factors in the Minimum Requirements by introducing calcium ion into the test medium.


Semi-micro plaque neutralization test for rubella antibody. Attenuated rubella virus, strain Cendehill, was found to produce small, distinct and ring-shaped plaques in Vero cell cultures. This finding was utilized to develop a semi-micro plaque neutralization test for a rubella antibody in 14 cmX9cm (24 wells) plastic trays. The procedure represents a reproducible and economical way to measure rubella neutralizing antibody.


Endotoxin, histamine-sensitizing factor and lymphocytosis-promoting factor contents of pertussis vaccines produced in Japan. The amounts of endotoxin, histamine-sensitizing factor and lymphocytosis-promoting factor contained in combined diphtheria-pertussis-tetanus and combined diphteria-pertussis vaccines recently produced in Japan were determined and the relationships among them were statistically analyzed. The estimated values in histamine-sensitizing units (HSU) and lymphocytosispromoting units (LPU) per human dose ranged from 0.3 to 6 and from 0.4 to 5, respectively. A fairly wide range of endotoxin contents, which were expressed in body weight-decreasing units (BWDU), was also demonstrated. All the ranges were larger than those expected from experimental error. There was a positive correlation between the HSU and LPU values although the individual HSU-LPU ratios ranged from 0.3 to 3, but the range was markedly larger than the width of the 95% confidence interval of the mean ratio. Negative correlation between BWDU and LPU was also significant, probably because of the relatively large number degrees of freedom, though the coefficient was fairly small; while that between BWDU and HSU was not significant. The frequency distribution of individual values of HSU was divided into two lognormal distributions. With one of the two groups obtained by this subdivision, a distinct positive correlation bewteen HSU and LPU was demonstrated, but with the other group there was little correlation. Some differences between the two groups were also found in the correlations between BWDU and the other two variates. No factors responsible for the separation of the groups have yet been found.


Isolation of orthomyxoviruses from migrating and domestic ducks in northern Japan in 1976--1977. Ortho- and parmyxoviruses were isolated at high frequencies from cloacal and tracheal samples of 334 domestic and 161 migrating ducks in Miyagi and Akita Prefectures, Japan, in the winter of 1976--77. Forty-four hemagglutinating agents were isolated from these ducks. The frequency of virus isolation was much higher from the cloacal samples (6.3%) than the tracheal samples (2.6%). However, no significant difference was found in the isolation ratio between the domestic (7.8%) and migrating (6.8%) ducks. Nine strains of the hemagglutinating agents were identified as influenza A viruses and confirmed to be in pure form by complement-fixation (CF) tests and from their polypeptide profiles. The antigenic characterization of the influenza A viruses revealed the presence of several subtypes; Hav5Nav-2-3, Hav6Neq2, Hav6N2, Hav7Neq2 and Hav7N2.


Neuraminidase effect on the growth of a transplantable nickel sulfide-induced rat tumor. Exposure of a weakly immunogenic nickel sulfide-induced Fischer rat tumor to Vibrio cholerae neuraminidase inhibited tumor growth in normal recipients. These recipients were found to be more resistent to a subsequent tumor inoculation.


[Structure of chromosomal deoxyribonucleoproteins. IX. Heterogeneity of chromatin subunits in vitro and location of histone H1]. Chromatin subunits ("nucleosomes") isolated from a mild staphylococcal nuclease digest of chromatin by a sucrose gradient centrifugation have been studied. We found that such preparation contains nucleosomes of the two discrete types which can be separated from each other by a low-ionic-strength polyacrylamide gel electrophoresis. Nucleosome of the first type contains all five histones and a DNA fragment 170--180 base pairs long, whereas nucleosome of the second type lacks histone H1 and its DNA fragment is approximately 140 base pairs long. Purified dimer of the nucleosome (dinucleosome) can be fractionated by gel electrophoresis into three discrete bands which correspond to dinucleosomes, containing two, one and no molecules of H1 histone. Similar heterogeneity with respect to the content of histone H1 probably exists in the case of larger oligonucleosomes. These and related findings strongly suggest that the H1 molecule is bound to a short (30--40 base pairs) terminal stretch of the nucleosomal DNA segment which can be removed by nuclease (possibly in the form of H1--DNA complex) without any significant disturbance of the main structural features of the nucleosome.


[Kinetic method for the determination of sequences of purine and pyrimidine blocks for circular nucleic acids]. We prove that the sequence of purine and pyrimidine blocks can be restored for circular nucleic acids if molecular weight distributions of fragments of various stages of hydrolysis are known. Hydrolysis of nucleic acid is considered as a progressive fragmentation of a "ciphering", an arbitrary circular polymer, monomers of which have weights from 1 to 6 (corresponding to the real number of purines or pyrimidines in the block), while the site of fragmentation is selected at random. The hydrolysis of circular RNA under the action of pancreatic RNase proceeds in accordance with the model of ciphering. Heuristic method for restoration of the monomer sequence in the ciphering based upon some characteristics of molecular weight distributions (such as Sj(m)-number of the fragments with the weight m containing j unbroken bonds) is considered. Uniqueness of restoration of the monomers sequence of the ciphering based upon known set [Sj(m)] is proved.


[B-A transition of DNA in aqueous solutions of nonelectrolytes]. Circular dichroism spectra of DNA in ternary water-nonelectrolyte solutions (water--ethanol--isopropanol and water--ethanol--dioxane) show that the decrease in water content at various nonelectrolyte ratios leads to the transition of DNA from B- to A-form. Water activity values in B-A transition region were calculated. The transition takes place within the range of water activity and DNA conformations have been plotted on triangular diagrams.


[A comparative characteristic of DNA pyrimidine sequences of shark, protopterus and perch]. Pyrimidine sequences of DNA from three fishes: shark, protopterus and perch have been studied. These data together with the evidence from the literature were used to support earlier conclusions that dipnoi and cartilagenous fishes should be distinguished as independent classes. The clustering index, beta, and the total molar percentage of long pyrimidine oligonucleotides (Z) containing greater than or equal to 8 nucleotides--a new parameter offered by us--have been used in comparative investigation of DNAs. The new parameter has permitted to obtain a higher resolution in the analysis of our own and literature data on DNA pyrimidine clusters in fishes. Investigation of pyrimidine clusters and of the base composition of individual isoplits of these clusters using statistical analysis showed that DNA from shark, protopterus, sturgeon and perch significantly differ by many features. Significant differences between these DNAs were found also in the base composition. Thus, new evidence for distinguishing cartilagenous fishes and dipnoi as independent classes have been received.


[Quantitative relationships in the theory of active transport]. Quantitative relations for the active transport across a membrane are derived according to Mitchell's theory using an approach based on thermodynamic and kinetic principles. The main formula predicts that the flow rate depends on the "oxidative power" of the membrane in case of a big ionic flow. In case of a low current the rate is determined by the redox potential of the respiratory substrate. The relations derived in the paper are in qualitative agreement with Kaback's data on the active transport in bacterial vesicles.


[Compact form of DNA in solution. X. Peculiarities of circular dichroism spectra of DNA compact particles forming polyethylene glycol-containing water-salt solutions]. The experimental data indicating that the amplitude of the negative band in CD spectra of DNA compact particles forming in PEG-containing water-salt solutions intensifies with the decrease of DNA molecular weight are presented. This effect is not explained by the light scattering on the compact particles. The presence of the negative band in CD spectrum of DNA compact particles is interpreted as result of formation of dichrographic-active "microcrystalline" region ("domains") (if DNA compact particles are formed from double-stranded molecules with unaltered secondary structure); it is also supposed that the number of these regions in the particle and their dichrographic activity doesn't depend on the particles size. This interpretation is in agreement with experimental data on the increase of the number of compact particles with the decrease of DNA molecular weight. Proportionality coefficient in the linear dependence of the amplitude of negative band on the size of DNA compact particles in solution depends apparently on dichrographic activity of "microcrystalline" regions, and this activity is connected with structural peculiarities of initial DNA molecules.


[Nucleotide composition and digestion by nucleases of RNA from muscle amylose isomerase]. The primary structure of homogeneous low molecular RNA preparation with the sedimentation coefficient 2.5S isolated from amilose isomerase (A1) of muscle (E.C. 2.4.1.18) was analysed. This RNA can be digested by venom phosphodiesterase as well as by pancreatic and T2 RNAases; hence we conclude that the polynucleotide chain of A1 RNA consists of 3.5-phosphodiester bonds common for all RNAs. The nucleotide composition of the RNA was studied by two-dimensional TLC followed by spectrophotometry. The results show that its chain is 31--32 nucleotides long. High content of unusual components (about 30%) and guanine (about 40%) are specific features of this RNA.


[Kinetics of the order-disorder transition in the system of two interacting macromolecules (computer simulation)]. Kinetics of the model reaction between oligomeric planar lattice-model chains has been studied by Monte--Carlo method. Simulation of the chain's motion was performing using rules of Verdier--Stockmayer. The length of chains has been varied from 8 to 24 beads. The probabilities of breaking of a contact between two chains was given by w=exp(--U); the formation of an adjacent contact was controlled by mobility of chains. The probability of the formation of any isolated contact was given by w0=exp(--U0). Kinetic curves were obtained for mean number of contacts Z(t) with different initial conditions and U, U0 values. The estimation of mean rates of formation-breaking of contacts (V+ and V-) and their dependences on the time, U and U0 have been obtained. Rate constants for the formation-breaking of a contact (k+ and k-) were estimated as well as the distribution for k+/- over states of the binary complex. The calculations were made for the case of homopolymers, intrachain interactions were omitted.


[Conformational transitions in adsorbed macromolecules with secondary structure]. An analytical theory is presented taking into account the effects of the flat adsorbing surface on the equilibrium properties of the long single-stranded macromolecule possessing a secondary structure. Change of the secondary structure is described in terms of Zimm--Bragg theory; adsorbtion properties are calculated for the lattice model without taking into account the 3-dimensional interactions. It is shown that the presence of the adsorbing surface sharpens helix-coil transition, displacing it towards the lower constants of equilibrium (s). A relation of the critical energy of adsorbtion (--epsilonkappa) on s is obtained at different values of the cooperativity factor sigma. This relationship represents a phase diagram of the system. Various sections of this phase diagram corresponding to different dependence of s and --epsilon on the external factors are considered. It is shown that the process of adsorbtion may occur in different manners: either cooperatively or by the phase transition of type II with jumps in one or in three points.


[Nuclear ribonucleoproteins containing messenger RNA. 12. Fluorescence studies of the secondary structure of pre-mRNA in nuclear RNP-particles]. Secondary structure of pre-mRNA in nuclear ribonucleoprotein particles (30S-particles) was examined using fluorescent dyes: acridine orange, acriflavine and ethidium bromide. Comparison of ethidium bromide and acriflavine adsorption isotherms for RNP-particles and free RNA and a study of acridine orange dimerization on binding to RNP revealed that 70% of pre-mRNA in 30S-particles is accessible for the dye binding. Dye molecules were adsorbed on double-stranded sequences (11--12% of the total amount of RNA in 30S-particles) and on the single-stranded parts of RNA (58--59% of 30S-particles), the rest part of RNA was unaccessible for the dye binding. A method involving measurements of acriflavine fluorescence quantum yields was used for the determination of nucleotide composition of double-stranded parts of RNA in the 30S-particles. AU-nucleotide content thus obtained was approximately 50%, as was established also for free pre-mRNA. Na+ ions weaken the interaction between the protein and pre-mRNA in 30S particles and increase mobility of double-stranded parts of this nucleic acid.


[Properties of different classes of low molecular weight RNAs]. Low molecular weight (LMW) RNAs from early fish embryos were characterized by investigating their migration in polyacrylamide gels, solubility in 1.5 M NaCl, in vivo methylation by the methionine methyl group, metabolic stability, and effects of low doses of alpha-amanitin on their syntheses. At blastula stage, the mature tRNA and 4.3--4.8 S metabolically unstable molecules described as precursors of tRNA in pulse-chase experiments were found. The syntheses of stable methylated LMW RNAs, different from tRNA, were also shown. The sizes of these molecules, determined by their migration in polyacrylamide gels, were 5.3S; 5.8S; 6.3S and 6.9S These RNAs resemble the nuclear LMW RNAs, discovered in different animal cells, in infertilized eggs and developing embryos of sea urchin among them. The data obtained allow one to suppose an existance of a maturation stage during formation of these RNAs. The synthesis of a certain fraction of LMW RNAs (4.9S) was sensible to low doses of alpha-amanitin and therefore involved RNA-polymerase II.


[Autocatalytic enzyme reactions].

[Autocatalytic enzyme reactions]. Kinetic aspects of enzymatic reactions proceeding in the autocatalytic mode are considered. Kinetic analysis of a mechanism with proenzyme-enzyme interaction and of mechanism in which activation involves an interaction with the product of enzymatic reaction is presented. It is shown that these mechanisms are distinguished by the dependences of kinetics of the process on enzyme and substrate concentrations. Method is developed for the determination of concentration of active centers of enzyme in the case of activation by reaction product. Conclusions obtained are illustrated using autocatalytic enzymatic systems such as trypsin-trypsinogen and bacterial hydrogenases-hydrogen-4,4'-dimethylbipyridinium.


[Proteolytic mechanism of deproteinization of influenza virus by plasmatic membranes]. A mechanism responsible for proteolytic deproteinization of influenza virus A2 Hong-Kong (I)68 by plasmatic membranes of sensitive cells was studied. Presence of trypsinlike protease in plasmatic membranes of white mice lungs was demonstrated. A considerable inhibition of the membrane proteolitic activity was obtained in the presence of epsilon-aminocaproic acid. Disintegration of the virus labeled by [3H]uridine by plasmatic membranes was investigated and it was found that this process required ATP. Inhibition of the protease activity by epsilon-aminocaproic acid led to the suppression of deproteinization of influenza virus. The experimental data obtained indicate that the proteolytic enzymes of plasmatic membranes participate in the complex process of virus "uncoating".


[Simple procedure for the isolation of animal mitochondrial deoxyribonucleic acid]. A simple procedure for the isolation of animal mitochondrial DNA is described. It includes deproteinization of mitochondrial lysates with phenol, precipitation of total nucleic acids with polyethylene glycol, RNA precipitation by saet and final purification of DNA using gel chromatography on a Sepharose 4B column. MtDNA preparations obtained were free from protein and RNA and were represented predimonantly by the covalently closed molecules. The content of D-looped molecules in these preparations was equal to 45%.


[DNA compact form in solution. XI. Melting of the DNA compact state, formed in water-salt solutions, containing poly(ethylene glycol)]. Temperature dependences of absorption and CD spectra of DNA compact particles, formed in water-salt solutions in the presence of poly(ethylene glycol) (PEG), have been compared. It has been shown that the disappearance of a specific negative CD band, characteristic of the DNA compact form, occures prior to the destruction of the DNA secondary structure and is not connected with changes of the number or the size of compact particles. The disappearance of this band is believed to reflect the destruction of ordered structure of microcrystalline regions in DNA compact particles. The temperature, at which this "melting" takes place (taum) increases with the rise of PEG concentration, but always remains below the melting temperature of the DNA secondary structure. The thermodynamic parameters, deltaH and deltaS, which characterize the "melting" of the microcrystalline regions in DNA compact particles, were calculated for each CD "melting" curve and were shown in increase, similarly to taum, with the rise of PEG concentration. These data indicate that the regularity of the internal structure of DNA compact particles depends not only on the structural characteristics of the initial DNA, but also on the solvent properties, in particular, on the PEG concentration.


[Kinetics of reactions in multienzyme systems. I. Steady state processes in bienzyme systems. Lineal multienzyme sequences]. Kinetic aspects of reactions in multienzyme systems are discussed. Detailed formal-kinetic discription of bienzyme system is made for the steady-state conditions. Two important cases--constant and variable concentration of initial substrate are discussed. The criteria for realization of steady-state condition of system are formulated. Equations which describe the steady rates and steady state concentrations of intermediates as functions of initial concentrations and kinetic parameters of individual enzymes were developed. The time range of steady-state conditions was estimated and methods for the determination of kinetic parameters of enzymes in steady-state condition were developed. The regulation aspects of bienzyme system are considered. An analysis of reactions kinetics in lineal multienzyme systems was made and criteria of steady-state condition were formulated. Methods of determination of kinetic parameters Vmax and Kmax for each individual enzyme of multienzyme system were developed. The principle of limiting step was formulated quantitatively, criteria and methods of the finding of limiting step were developed.


The Brazelton Neonatal Behavior Assessment Scale: introduction. In summary, the Neonatal Behavioral Assessment Scale attempts to capture the complexity of behavioral responses to social stimuli as the neonate moves from sleep states to crying and to alert states of consciousness. The 20 relfex items tap neurological intergrity. The 27 behavioral items attempt to assess the neonate's capacity to respond to the environment. As such, these item scores become a reflection of the baby's capacity to organize his or her autonomic and central nervous system in order to respond to stimuli (both animate and inanimate), and the exam is used to predict to the environment's response to the baby as an individual. Characteristic of this exam is that it scores the infant's "best" performance, which is captured after a series of trials often without a fixed order, and assesses the baby's capacity to organize responses within different states of consciousness.


[Role of water in the thermal instability of DNA]. We studied structural changes of DNA heated for long times at temperatures between 20 to 100 degrees C at different relative humidities (range 0--100%). DNA structure was analyzed by the following criteria: solubility changes, optical melting, ultraviolet spectroscopy, potentiometry and equilibrium dialysis. It has been found that irreversible changes in DNA secondary structure take place at around 37 degrees C, temperature optimal for the function in many living systems. These irreversible changes may be interpreted as a consequence of formation of interchain contacts (non-covalent "cross-links"). We demonstrate that the whole range of relative humidities may be divided onto three regions. For each of these regions DNA has somewhat different molecular structure and peculiarities are observed in the stabilizing and destabilizing action of water on DNA three-dimensional structure. Irreversible changes of DNA secondary structure as a function of bound water are represented by a bell-shaped curve. Similarity between this curve and a curve for the survival microorganisms is discussed.


[Protein factor from regenerating rat liver destabilizing secondary DNA structure]. In DNA preparations isolated from regenerating rat liver 22 hours after partial hepatectomy, i.e. at the period of the most intensive DNA synthesis a "Denaturating Protein Factor" (DPF) tightly bound to DNA was found. Isolated protein fraction with a molecular weight of 6500 dalton was found to be homogenous upon SDS-polyacrylamide electrophoresis. The degree of destabilisation of DNA was estimated by its reaction with water-soluble [14C]CME-carbodiimide which modifies selectively guanine and thymine residues only in the denatured DNA regions. Pronase treated DPF loses its DNA-denaturing capacity. Pronase treatment of DNA--DPF complex restores native DNA structure. DPF from rat liver was able to denature DNA from calf thymus and bacteriophage T7 DNA. A hypothesis is proposed that the DPF is responsible for the destabilization of DNA secondary structure in the process of replication.


[Molecular mechanisms of spontaneous transversions and transitions]. Molecular mechanisms of spontaneous base substitutions during template directed nucleic acid synthesis have been considered. For this purpose calculations of interaction energy in various coplanar base pairs with approximately such glycoside bond positions as for Watson--Crick base pairs have been carried out by means of atom-atom potential function method. A number of this energy local minima which could be realized in double helix during template synthesis have been found. The calculation results permit to present purine-purine pair formation with transition of one of nucleotides to syn-conformation as the main transversion pathway and formation of wobble pairs UG and AC as the transition pathway. A possible contribution of interactions between base pairs and enzyme to fidelity of template synthesis have been evaluated. Calculation results are in accord with experimental data on spontaneous mutation frequencies of errors in nucleic acid synthesis in vitro.


[Nucleoprotein melting. II. Melting of irreversible DNA-protein complexes]. Three with different complexity models: single-stranded, periodic theeropolymer, two-stranded periodic heteropolymer and complex of DNA with irreversible bound proteins have been considered. It is shown that the individual bands on the differential melting curve appear if the length of protein bound regions exceed 25 base pairs. In this case the melting temperature of free and protein bound regions depends on their reciprocal length in almost linear manner. Moreover, the temperature of the peak corresponding to the protein bound regions is independent on the length of the adjacent free DNA regions if their length exceeds 15 base pairs. If the length of free and protein bound regions exceed 300 base pairs, their melting temperatures becomes almost equal to that of infinitely long polymer with the analogous structure. A simple method for determination of length of the free and the protein bound regions length has been proposed.


II. Assessing an assessment: conceptual considerations, methodological issues, and a perspective on the future of the Neonatal Behavioral Assessment Scale. The Brazelton Neonatal Behavioral Assessment Scale is a behavior analysis instrument which provides the researcher with a systematic way of eliciting and documenting a series of complex behavioral parameters reflecting the healthy term newborn's current repertoire of organization and functioning. This assessment focuses on the newborn's adaptation as a social interactive organism embedded in a feedback system with an adult caregiver. It brings out those processes which the individual newborn uses to deal with his animate and inanimate environment and yields a series of defined and scaled behavioral descriptors which permit quantification of aspects of behavioral parameters reflecting such subsystems of functioning as physiological organization, motoric organization, state organization, and interactive organization. As such, it provides a window on the complexity of current organization of the human newborn. It does not provide a ready-made method of synthesizing the information gained about the individual newborn. It becomes the researcher's task to develop a synthesis method appropriate to the question under investigation.


[Nuclear ribonucleoprotein particles containing messenger RNA. 12. Studies of dissociation and reconstruction of 30S particles]. Protein of purified 30S particles analyzed by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis is present mainly as two bands with the apparent molecular weight of 38 000 and 41 000 daltons. These bands contain not less than 90% of the total protein. When the same material is electrophoresed in the presence of urea (pH 4.5) it migrates as one homogeneous band. The procedure for isolation of free informofers in preparative scale is described. The free informofers do not contain rapidly labeled RNA and are not stable: they dissociate reversibly into protein subunits of lower molecular weights. The dissociation is concentration dependent: low concentration of protein facilitates the dissociation process. Both whole informofers and their protein subunits easily interact with free pro-mRNA yielding 30S RNP. However only the product of reconstruction with informofers is similar to native 30S particles, according to several biochemical tests. These data support the model of the structure of nuclear RNP particles according to which pro-mRNA is distributed on the surface of globular protein particles.


IV. Issues in grouping items from the Neonatal Behavioral Assessment Scale. The various analyses of the NBAS that we have described do not permit any simple understanding of the significance of the scales. We have shown that other variables associated with the scale may have more significance than the scales themselves. Predominant state appears to be one of these variables. When the NBAS scores are correlated with behavior only 4 months later, only tiny relationships are evident, and, what is more, many of these relationships do not make obvious sense. In recent times there has been growing evidence that infant behavior shows little consistency or continuity over time (McCall, Eichorn, & Hogarty 1977). These data from the Brazelton NBAS seem to conform that notion. The message we want to end with is that we have still not reached the point where we can adequately understand the behavior of the human newborn. Simple relations between antecedent and consequent behaviors assessed by simple statistical procedures will not solve our problem. Bridging the gap between our global theorizing about newborn behavior and concrete deomonstrations of those theories will require a complex interplay of common sense and statistical sophistication.


[Nomographs for determination of sedimentation constants of nucleic acids by means of centrifugation in sucrose gradients using the "Sinco" ultracentrifuge]. A set of nomographs for determination of standard sedimentation constant values for DNA and RNA directly from the results of centrifugation without any marker is calculated and plotted for 9 Spinco bucket-rotors, 5 temperatures, and two commonly used sucrose gradients (5--20 and 15--30%).


[Extra-intracranial artérial by-pass. A clinical experience based upon 40 cases (author's transl)]. Extra-intracranial by-pass between a branch of the external carotid artery and a branch of middle cerebral artery has been used since 1972 in the treatment of cerebral ischemia. 40 patients have been operated on (34 men and 6 women) aged from 28 to 68. Clinical data were TIA's or PRIND in 11 patients and stroke in 29 patients. The left hemisphere was involved in 25 cases and the right one in 15 cases. No patient was operated on in emergency; operation was performed after 2 or 3 weeks in most cases. The branch of external carotid artery was the superficial temporal artery in 36 patients and the occipital artery in 4 patients. As for the cerebral artery, were used the anterior temporal artery (9), the middle temporal artery (2), the posterior temporal artery (15), the angular artery (6), a frontal artery (15) and a parietal artery (1). In 8 patients, two anastomosis were performed using both branches of STA. Patency of the by-pass was confirmed in most cases by means of angiography, performed early after operation, and if possible one year later.


[Extra-intracranial arterial bypasses. Evaluation of their permeability by use of the Doppler effect]. 40 temporo-sylvian anastomoses were controlled using Doppler ultrasonic examination. The results are compared to post-operative arteriograms. The Doppler examination has proved to be highly accurate when compared to contrast arteriography in the survey of extra-intracranial anastomosis. This non invasive procedure can easily be repeated. However the size of the revascularized area cannot be estimated. The simultaneous isotopic studies of regional cerebral blood flow could provide a means of quantifying the results of the anastomoses.


[Direct surgery of traumatic injuries of the radial nerve (author's transl)]. 33 cases of traumatic lesions of the radial nerve are reported. Etiological features, prognosis, surgical treatment including micro-surgical techniques, leading to a larger indication of direct nerve repair are discussed. Recent nerve wounds must be repaired early. Surgical exploration will be carried out on unopened lesions when no recovery occurs within two months. According to the lesion, peri-fascicular neurolysis or fascicular resection-graft will be achieved. Tendon transfer techniques will be proposed only after one or two years without recovering, according to the level of the injury.


[Diastematomyelia. About a series of 6 cases (author's transl)]. The authors report 6 cases of diastematomyelia in children. They stress the rarety of this spinal cord diformity whose pathogenesis is obviously of dysraphic origin. From the clinical point of view, "orthopedic syndrom" is the most common complaint (cypho-scoliosis and - or - malformation of the feet) in a child with dorsal or lumbar cutaneous dysplasia. Neurological disorders or sphincterian disturbance are less frequent. Radiologic examination shows the high frequency of spina occulta. The diagnosis is assessed when bony spur is demonstrated on films. Vertebral body diformities are not constant and often far seated from spur. Air myelography demonstrates site and length of spinal cord cleft and often the low position of conus medullaris. Surgery allows the liberation of bifid cord by resection of spur. It should be suitable to cut filum terminale when it is accessible by laminectomy. Exposure of results stress the preventive effect of surgery for diastematomyelia.


[Medulloblastoma in childhood. Survival rates and functional results (author's transl)]. The authors report on a series of 57 medulloblastomas operated upon in children from 1964 ot 1976. Among these children, 44 completed the treatment with radiotherapy of the whole central nervous system. The post-operative mortality rate in 10,5%. Postoperative death occurred mainly in infants or when the tumor involved the brain stem. The five years survival rate is 46,6% in the whole series. It raises up to 50% in the series of the patients who completed the treatment with radiotherapy. The study shows that the life of survivals is frequently impaired by mental or behavioural disturbances. I.Q. varies from 70 to 90 in 66% of the children; it is below 70 in 20%. Behavioural disturbances are found in 91% of cases, wrong space orientation, speech or writing disabilities in 87%. In order to evaluate the responsibility of ray therapy in the development of these sequelae, the results have been compared to those of a series of cerebellar astrocytomas surgically removed, but not irradiated. The comparison shows that radiotherapy is at least partially responsible for the mental and behavioural disturbances.


[Compression and obstruction of the internal carotid artery by sellar and parasellar tumors]. It is classicaly admitted that the intracranial internal carotid artery after a first intracavernous segment, becomes intra-dural by perforating or passing through the dura. Since 1949, the first of us has refuted this conception as well as that of the artery floating in the venious blood of the cavernous sinus and has described to so-called cavernous sinus as a latero-seller extradural space into which the artery has but neighbourhood relationship with a venous plexus. During embryonic development the internal carotid artery is englobed by the dura which differentiates around the cerebral vessels. At a later stage, owing to the adhesion of the dural leaf to the intracranial periosteum, the internal carotid artery becomes closely attached to the bone at the level of the base of the anterior clinoid process. This explains that tumors developping in the sellar and parasellar region may compress or obstruct the carotid artery at this level causing neurologic symptoms of ischemic origin. Three similar cases are reported, a glioma of the optic nerve, an adenoma of the hypophysis and meningioma of the sphenoidal wing.


[Inter thalamo-trigonal approach to the third ventricle (author's transl)]. The exploration and surgical treatment of the lesions of the 3rd ventricle may be carried out without sectioning the anterior columns of the trigonum. The body of the trigonum and the choroid tissue are lifted sometimes at the cost only of the sectioning of the thalamostriated vein. The absence of mnesic trouble particularly in benign tumours of the third ventricle is the essential advantage of same. Access is very much wider particularly for the posterior part of third ventricle.