Crescents in diabetic glomerulopathy. Incidence and clinical significance. Crescents, defined as any proliferative or fibrous space occupying reaction of the parietal layer of Bowman's capsule, occur as a regular and integral feature of the glomerular changes of diabetes mellitus. The frequency of crescents and adhesions to the capsule increases with increasing total severity of diabetic glomerular and vascular disease in glomeruli with mild-moderate diffuse glomerulosclerosis (GS), severe diffuse GS, and nodular GA. The high frequency (greater than 90 per cent) of crescents and adhesions in glomeruli with exudative lesions is unrelated to over-all severity of diabetic renal disease. The 8.73 per cent of glomeruli with exudative lesions had 45 per cent of the total crescents observed. The mechanism of crescent formation in diabetes is probably similar to the proposed pathogenesis of crescents in other renal diseases. The underlying injury in the glomerular capillaries in diabetes is mainly the "exudative lesion." The percentage of diabetic glomeruli with crescents correlated better with blood urea nitrogen and creatinine that did the percentage of end stage glomeruli (a measure of severity of vascular disease), the percentage of diabetic glomeruli with severe diffuse GS, the percentage of diabetic glomeruli with nodular GS, or the percentage of diabetic glomeruli with exudative lesions. The percentage of diabetic glomeruli with crescents correlated better with severity of vascular disease than did any of the other diabetic glomerular changes. No correlation existed between incidence of crescents and "capsular drops."


Morphometric and autoradiographic study of developing ventricular and atrial myocardium in fetal rats. The ventricular and atrial myocardia of 19- to 21-day-old rat fetuses have been studied by electron microscopic morphometry and quantitative autoradiography following the injection of 3H-leucine. The myocytes in both these regions contain numerous myofibrils located predominantly near the sarcolemma and oriented parallel to each other and to the long axis of the cell. The width of myofibrils at this stage of development is 0.428 +/- 0.240 mum. in the ventricle and 0.365 +/- 0.185 mum. in the atrium. The volume fractions of myofibrils, mitochondria, smooth endoplasmic reticulum, sarcoplasmic matrix, and sarcolemma in ventricular myocytes are nearly equal to the corresponding fractions in atrial cells. A similarity between ventricular and atrial myocytes was also found in the distribution of newly synthesized proteins as indicated autoradiographically by the concentration of grains over various sarcoplasmic structures. In both tissues the concentration of grains was consistently above average over the sarcolemma, smooth endoplasmic reticulum, and myofibrils; average over the mitochondria; and below average in association with the sarcoplasmic matrix. The specificity of this autoradiographic procedure for labeled amino acids actually incorporated into protein was tested biochemically, and it was found that glutaraldehyde-paraformaldehyde fixation leads to a negligible contamination with non-specifically bound leucine. It is suggested that the high concentration of protein labeling near the sarcolemma is related to the imminent development of the T-system and its associated channels of sarcoplasmic reticulum.


Alterations of the renal papilla during mercuric chloride-induced acute tubular necrosis. Marked morphologic changes were seen in all structural elements of the renal papilla during mercuric chloride-induced acute tubular necrosis. Expect for the descriptions of increased numbers of leukocytes within the medullary vasa recta, papillary changes have not been described previously. The techniques used in this study included light microscopy, scanning electron microscopy, and transmission electron microscopy. The renal interstitial cells developed an extremely irregular contour and were penetrated by large irregular cavelike structures. A marked decrease occurred in the size and number of the cytoplasmic lipid droplets in these cells. The volume of the Golgi area, and of the rough and smooth endoplasmic reticulum increased. The morphologic changes in the renal interstitial cells were indicative of increased activity rather than of cellular injury. This is of insterest because several investigators have postulated that the interstitial cells are the site of renal prostaglandin synthesis Incrreased prostaglandin synthesis and release have been proposed to play a role in the redistribution of renal blood flow seen during acute renal failure.


Development of lymph hypertension during lymphatic occlusion. The effects of obstruction of lymph flow on the intralymphatic pressure are studied through a mathematical model using a digital computer and intralymphatic pressure was observed to increase.


Xeroradiography of the lymphatics.

Xeroradiography of the lymphatics. Lymphograms of 40 patients were made on xeroradiographic plates and conventional X-ray films. Both imaging procedures are compared in regard to their spatial and contrast resolution. Although xeroradiography offers little advantage in retroperitoneal lymphography, it essentially improves imaging of brachial lymphatic vessels and lymph nodes.


Lack of genetic control of the lymphatic pathway. Studies on rats. The lymphatic route from the testis to the cisterna chyli is studied in two inbred and one random bred strain of rats. The pathway varied similarly in all three groups with no indication of genetic control.


Electrophysiological responses from the cochlea and inferior colliculus in guinea pigs after head injury. Electrical responses from the inferior colliculus (ER) and round window (CP) to acoustical stimuli were compared in control and experimental guinea pigs which had received a single blow to the freely movable head. After the blow to the head, all of the animals showed signs of commotio cerebri, and some of them died. The experimental animals were divided into two groups so that the physiologic responses to sound could be evaluated one day (early group) and seven days (intermediate group) following the head blow. The animals of the early group had elevated ER thresholds over the entire frequency range tested with an average threshold of 37.8 db. The animals of the intermediate group also had elevated ER thresholds which averaged 23.9 db. Input-output intensity function of ER for the experimental animals showed a recruitment-like phenomenon. The CP thresholds in the injured animals did not differ significantly from those in the control group. Damage to the VIIIth nerve and higher central pathways is very likely a more frequent cause of the otoneurologic manifestations following head injury than end organ damage.


alpha and piDL helical states of alternating poly(gamma-benzyl D-L-glutamate) in solution. As in solid state, strictly alternating poly(gamma-benzyl D-L-glutamate) in solution can adopt two different helical conformations. Besides the alpha helix, a second helical conformation is found at higher temperatures in dioxane and chloroform, the properties of which correspond to that of the piDL4 helix. As the molecules have a finite length a screw sense is favored for both helical forms thus giving rise to optical activity allowing the study of the transconformation by optical rotatory dispersion and circular dichroism besides infrared and dielectric measurements. Thus, as the temperature is raised the equilibria right-left handed alpha helices and alpha-piDL helical forms can be followed. The favored screw senses are determined by the number of interacting side chains for the alpha helix and by the number of hydrogen bonds which are formed in the piDL helical conformation. The side chain-side chain interactions in the alpha helix are experimentally shown to be attractive.


Bell's palsy and the chorda tympani nerve: a clinical and electron microscopic study. The chorda tympani nerve plays an important role in the pathogenesis of Bell's palsy. The chorda tympani nerve is altered early in the course of the disease, perhaps before involvement of the facial nerve occurs. This was demonstrated by studying the pathophysiologic alterations of the chorda tympani nerves of 15 patients with Bell's palsy. Fifty-seven percent of the patients noted taste aberrations two days before the onset of the facial paralysis. In addition, chorda tympani nerve function, tested by electrogustometry and by determining submandibular salivary flow, was altered before the response to nerve excitability became reduced; further, the electron micrographic findings in two patients indicated that the involvement of the chorda tympani nerve preceded the time of onset of the facial paralysis. The study established a relationship between the pathologic involvement of the chorda tympani nerve and the facial nerve. There was a direct relationship between the severity of changes noted microscopically in the chorda tympani nerve specimens and the ultimate recovery of facial motor function. Examination of the chorda tympani nerve specimens was used to correlate the effectiveness of treatment. The results of steroid therapy and surgical decompression were compared. Steroids had no beneficial effect. Complete return of facial function was associated with surgical management when surgery was performed based on reduced salivary flow to 25 percent of normal and while the response to maximal stimulation was still normal.


Otologic history, audiometry and tympanometry as a case finding procedure for school screening. An algorithm for identification of hearing loss and middle ear effusion based on otologic history, audiometry and tympanometry was designed and tested on 771 first grade school children. Each ear was profiled as being normal, at risk, or in need of otologic referral based on test-retest screening. In addition, each child was categorized on the basis of the worse ear. Results showed 57 percent of the children as being normal; otologic referral was indicated in 14 percent. The remaining children (29 percent) were at risk or at high risk. The combination of medical history, audiometry and tympanometry constitutes an excellent case finding procedure for screening the otologic status of young school children. Through the utilization of specific criteria, optimal referrals can be made, thereby providing better health care.


High-resolution nuclear magnetic resonance studies at 270 MHZ of alternating and random poly(benzyl D,L-glutamates). The solution conformations of several D,L copoly benzyl glutamates both random and alternating are studied by comparing their NMR spectra in chloroform and also in dioxane and dimethylformamide. The alpha CH chemical shifts characteristic of the alpha helix of strictly alternating DL copolymers in chloroform/0.5% TFA are established (3.65 and 3.82 ppm) and differ from that of the regular alpha helix (3.92 ppm). It is concluded that alternating copolymers prepared by an essentially racemization-free method are completely in the alpha-helical conformation which is characteristic of strictly alternating D-L copolymers, whereas random copolymers are largely regular alpha. The alpha leads to piDL helix/helix transition of an alternating copolymer in dioxane has been monitored and the alpha CH resonance characteristic of the piDL helix is found to be at the unusually low chemical shift of 4.45 ppm.


Surgery for chronic hyperplastic rhinosinusitis. Davison pointed out in 1953 that his purpose in treating sinusitis was to utilize the smallest amount of surgery that would produce permanent relief of symptoms. By 1963 he had become convinced that extensive disease required extensive surgery. Hyperplastic rhinosinusitis is treated by a variety of surgical techniques including polypectomy, turbinate cautery, submucous resection of the turbinates or nasal septum, anterior ethmoidectomy, and spheno-ethmoidectomy. Sixty-eight patients are presented who have undergone bilateral sphenoethmoidectomy between January, 1969, and January, 1974. These patients were predominantly allergic, with a high percentage of previous polypectomies and desensitization which failed to control their recurring nasal polyps. Ten patients were lost to follow-up. Forty-seven of 68 patients have had no recurrence of polyps in from 12 to 60 months. All patients continued to have mucosal manifestations of allergy or infection, but the recurrence of late polyps was limited to 11 patients. The spheno-ethmoidectomy technique is utilized, stressing complete removal of the middle turbinate. Kidder has shown an improved rate of polyp control in patients following ethmoidectomy with middle turbinate removal rather than with partial or total preservation of the middle turbinate. Complete resection of the middle turbinate with opening of the sphenoid air sinus permits a thorough exenteration of the ethmoid labyrinth and better control of chronic disease. A complication rate of 5.9 percent is presented and is deemed acceptable, since there no disabling complications or complications related to poor visualization.


Solid state side chain transitions of poly(alpha-amino acids). I. Investigation by differential scanning calorimetry. The differential scanning calorimetric behavior of a series of alpha-amino acid homopolymers and copolymers was investigated in the range of temperature from -80 to +130 degrees C. The following polymers have been examined: poly(N'-carbobenzoxy-L-lysine), poly(O-carbobenzoxy-L-tyrosine), random copolymers of O-carbobenzoxy-L-tyrosine and N'-carbobenzoxy-L-lysine, poly(Ngamma-carbobenzoxy-L-diaminobutyric acid), and poly(N sigma-carbobenzoxy-L-ornithine). Each sample exhibited a prominent glass-like transition between +30 and +60 degrees C with a specific heat increment deltacp of the order of 0.03-0.11 cal/(g degrees C). Endothermal peaks, developed by annealing, have been also been revealed. It is concluded that in poly(alpha-amino acids) side chain motions are capable of undergoing glass-like transition.


Spontaneous laryngeal disease in the canine. This report describes the type and incidence of spontaneous laryngeal disease in the dog. Signs of laryngeal disease are similar to those in other species. Dogs are usually presented with inspiratory obstructive dyspnea or stridor, since earlier signs are often missed. Severe, congenital abnormalities may occur unrecognized due to neonatal death. Subtle anomalies are seldom presented. Congenital paralysis of the laryngeal musculature has been seen in the Bouvier des Flandres and the Siberian Husky. Laryngeal obstruction occurs commonly in brachycephalic dogs (Bulldog, Boxer, Boston Terrier, Pug, Pikingese). The forshortened nasal cavity and pharynx result in reduced airway space. The result is inspiratory obstruction varying from noisy respiration to severe obstruction with cyanosis and syncope. Everted laryngeal ventricles are most common in these dogs. Mild degrees of ventricular edema are common in small breed dogs with lower respiratory disease and in field-trial Beagles due to voice abuse. Traumatic injuries to the larynx and hyoid apparatus are not rare. Bite wounds from dog fights are the most common cause. Compression fractures are rare, but injuries associated with shearing stresses, due to being shcken by the neck cause airway obstruction. These types of injuries include avulsion of the aryepiglottic folds, longitudinal tearing of the epiglottis, arytenoid displacement, hyo-laryngeal separation, and laryngotracheal separation. Delayed signs of recurrent nerve damage are common in severe laryngotracheal injuries.


Drugs and the otolaryngologist.

Drugs and the otolaryngologist. Numerous clinical problems arise as a result of our use of pharmaceuticals. They include untoward pharmacologic effects, socio-economic problems (excessive cost, abuse), improper administration and various medicolegal difficulties. Two areas of direct concern to the otolaryngologist are drug interactions and drug-induced diseases, problems which precipitate and prolong hospitalization and which introduce a new clinical entity, "diseases of medical progress." Otolaryngologic examples of these diseases are abundant; some are considered here in a brief explication of an area of growing concern.


Audiological evaluation following acupuncture for hearing loss. Six patients, diagnosed as having bilateral, sensori-neural hearing losses received audiological evaluations before and after acupuncture treatments. A comparison of mean pre- and post-treatment pure tone air conduction and speech reception thresholds indicated no significant improvement with respect to auditory acuity. Although most threshold shifts were within a +/- 5 db clinical error envelope, there was a general tendency for poorer hearing levels.


Laryngopharyngeal injuries.

Laryngopharyngeal injuries. The patient who sustains trauma to the neck may present with symptoms strongly suggesting an acute injury to the larynx. The laryngeal injury may be real or imagined; however, the clinical manifestations may be so overwhelmingly indicative of a laryngeal injury that a small tear in the adjacent upper gut may be overlooked. Failure to diagnose an upper gut injury can result in a confusing parade of symptoms and signs, great morbidity and even death. Two cases are presented, each illustrating certain unique aspects of upper gut and laryngeal injuries. The history, diagnosis, operative management and clinical course of each patient are described. Attention is given to the unique facets of each case which make upper gut injury a fascinating and challenging surgical entity. Each case is discussed in terms of diagnostic and management errors or areas of controversy. Finally, certain general concepts of management of upper gut injuries are described.


Meningoencephalocele of the paranasal sinuses. Meningoencephaloceles are not commonly seen by the otolaryngologist. They occur most frequently in the lumbosacral area where they are five times as common as in the occipital area. The anterior cranial presentation is quite rare. Most patients with meningoencephaloceles present early with large lesions and are treated by the neurosurgeon. Two patients are presented who had small meningoencephaloceles which are located in the paranasal sinuses and successfully treated by an extracranial approach. This approach is recommended for those lesions of the paranasal sinus where the resulting bony defect from the removal of the lesion is small and the sinus in not infected.


Evaluation of Fagara zanthoxyloides root extract in sickle cell anemia blood in vitro. An aqueous extract was prepared from roots of Fagara zanthoxyloides and examined for evidence of an antisickling effect in vitro. Addition of 25 mg/ml of the extract to fresh blood samples from sickle anemia subjects produced no change in the blood oxygen dissociation curves, and approximately equal percentages of sickled cells were observed at comparable oxygen saturation levels in the presence or absence of the extract. These observations fail to confirm previous reports describing an antisickling effect of root extracts of Fagara zanthoxyloides.


Plant-insect interactions. I. Biological and phytochemical evaluation of selected plants. Extracts from more than 325 different plants have been tested for their effects on larvae of Aedes aegypti, and from these initial tests, 16 plants were selected for further study. Extracts from plant parts of these 16 plants were screened using tlc and the results are tabulated along with the observed biological activity.


Akaloid screening. VII.

Akaloid screening. VII. One thousand and five plant extracts were screened for the presence of alkaloids. The number of positive tests obtained was 190, or 18.91%. There were 153 species found to contain alkaloids that are new to the literature. In the six previous communications (1-6) we have reported on the screening of 5,995 plant extracts for alkaloids. These extracts represented 4,888 species of plants, of which 1,336 gave positive alkaloid tests.


Experimental ulcerative disease of the colon. The oral administration to guinea-pigs of an aqueous solution of carrageenan derived from the red seaweed, Eucheuma spinosum, provides a useful, readily available experimental model for the study of ulcerative disease of the colon. Two types of ulcerative disease can be produced within a 4-6 week period, viz., ulceration localised mainly to the caecum by using 1% undegraded carrageenan in the drinking fluid, and extensive ulceration involving caecum, colon, and rectum by using 5% degraded carrageenan. Ulceration is probably due to the local action of carrageenan in the bowel.


[Quantifying the effect of antitussive drugs (author's transl)]. An experimental instruction for automatic recording of fits of coughing is being described. In contrast to the recording on a tape recorded mentioned on entering the above-mentioned installation is especially suited for short-term examinations. The advantages and disadvantages of this instruction for recording are being discussed.


Specific locus mutation rates after repeated small radiation doses to mouse oocytes. When female mice were given a dose of 20 X 20 rad X-rays, the specific locus mutation rate among offspring conceived up to 7 weeks after the end of treatment was 1/39887 or 0.18-10(-7)/rad/locus, whereas when the same total dose of 200 rad was given in a single exposure the mutation rate was 9/34813 or 1.85-10(-7)/rad/locus. The lower mutation rate after the 20 X 10 rad dose was obtained whether the total or 200 rad was given over a period of 5 days or 4 weeks, and if only young conceived in the first 20 days, rather than 7 weeks, were considered. It is suggested that each 10 rad fraction had the same small effect, and hence that these results confirm and extend RUSSELL's previous finding that the dose-response relationship for specific locus muations in females is curved.


DNA damage, DNA repair and chromosome aberrations of xeroderma pigmentosum cells and controls following exposure to nitrosation products of methylguanidine. Nitrosation of methylguanidine (MG) led to products that caused DNA fragmentation  (shift in sedimentation profiles of velocity centrifugation through alkaline sucrose gradients), a DNA repair synthesis (unscheduled uptake of (3H]TdR), chromosome aberrations and a lethal effect of cultured human fibroblasts. The response of repair-deficient xeroderma pigmentosum cells did not differ from that of controls. The nitrosation of MG must be carried out at a pH level below 3, in order to obtain products that react with cellular DNA. The results show that a DNA repair synthesis of human fibroblasts appears to be a sensitive assay for carcinogenic and mutagenic nitrosation products which may be formed within an organism from non-carcinogenic compounds.


Preparation of peritoneal cell metaphases of rats, mice and chinese hamsters after mitogenic stimulation with magnesium sulfate and/or aluminum hydroxide. A new cytogenetic system in vivo is presented using peritoneal cells, collected from unanesthetized rats, mice and Chinese hamsters, 48 h after an i.p. injection of a mitogen. The test is useful for periodic monitoring of chromosome aberration rates in the investigation of such problems as aging and chronic effects of mutagens and carcinogens. Among the 2 mitogens tested, aluminum hydroxyde was more efficient than magnesium sulfate in all 3 species. The rat is considered to be the most suitable animal for this test, in view of its easy handling, high cell yield and favourable response to mitogens. The spontaneous chromosome aberration rate in this animal was found to be comparable with that of bone-marrow cells.


The impact of induced mutations on human populations. The major impact of an increase in genetic damage will be expressed as an increase in autosomal dominant and X-linked traits as well as chromosomal disorders. The present incidence of dominant traits has been estimated at 1% of live births, but recent data from British Columbia indicate the true value in that population may be an order of magnitude lower. These estimates are important if one measures the damage in terms of doubling dose. Neither the average mutation rate nor the number of loci capable of mutating to dominant detrimental form is known. Mutations that cause sterility or early embryonic loss are detrimental in the Darwinian sense but have little impact on society. Mutations that are more fit biologically may be a heavy burden to society if the affected persons require medical or institutional care. Since exposure to some mutagens is unavoidable, these factors must ultimately be included in a cost-benefit analysis.


Some relations between teratogenesis and mutagenesis. The nonactinic environmental agents that have been found to induce mutations in laboratory mammals are almost without exception of a single chemical class, alkylating chemicals, whereas this class is only one of the numerous sorts of environmental agents that induce congenital structural malformations. Many other types of chemical teratogens as well as nonchemical teratogens exist. This conspicuous difference between the known means of producing these phenomena reflects the fact that the mechanism by which malformations and mutations arise are for the most part distinctly different from each other. Therefore, environmentally induced malformations and mutations cannot be equated with each other and used as mutual indicators in monitoring potential harmful effects of the environment.


Environmental mutagenesis: evolving strategies in the USA. A recent Environmental Mutagen Society report (the "Committee 17" report) made recommendations regarding the screening of environmental mutagens and the use of the resulting data. It is important in this respect to employ highly sensitive tests which detect heritable genetic damage of all possible molecular types. Mutagens of artificial origin which are being considered for continued production must be characterized with respect to their level and pattern of distribution and their persistence in the environment in order to perform realistic risk evaluations. Risk evaluation itself, particularly the summation of the effects of numerous distinct mutagens, may be assisted by adopting a common measure of mutagenicity such as the REC (rem-equivalent-chemical). Finally, the Committee 17 report laid out highly specific recommendations concerning maximum permissible exposures to environmental mutagens. Federal regulatory agencies and their enabling legislation are in fact evolving toward the effective control of this highly complicated problem.


Mutagenicity research and testing in Sweden. A survey is given of Swedish legislation for control of chemicals in the environment. Although no direct legal requirements for mutagenicity testing of chemicals exist at present in Sweden, such requirements can be enforced within the existing laws. Testing and research in chemical mutagenicity are especially performed at the Environmental Toxicology Unit of the Wallenberg laboratory, University of Stockholm. An outline is given of the organization of the unit, which is based on an interdisciplinary cooperation, among divisions of organic and analytical chemistry, cellular toxicology, and genetics. As examples of projects under joint investigation results on polychlorinated biphenyl (PCB) and on vinyl chloride are briefly described.


Hypothetical dose-response curves for chronic exposures to mutagens or carcinogens subject to simple enzymatic detoxification in the mammalian body. Dose-response curves for chemical carcinogenesis and mutagenesis in the whole mammal may be influenced (a) by processes affecting the delivery of the applied dose to the DNA of the target cell or (b) by processes affecting the response of the cell to the initial DNA damage. As an example of the former, the effect of a simple enzymatic detoxification system on the delivery to the target organ of an applied chronic dose has been considered. In certain circumstances as the applied dose is lowered, the delivered dose may become proportionately less than at high doses so that a new linear relation of lower slope is established. Such a biphasic curve is termed quasi-threshold to distinguish it from a true threshold. The slope at low doses could in principle be extrapolated to very low doses in the estimation of genetic risk.


Estimation of the effects of chemical mutagens: lessons from radiation genetics. Years of work with ionizing radiations have given us a wealth of data on radiation-induced mutations. These data, which have given insights regarding the mutational processes, should form the background for all mutagenesis work. In chemical mutagenesis, as in radiation mutagenesis, it is important to know the shape of the dose-effect curve in order to make further interpretations and calculations. It is also important to be on the constant alert for new relations that can be explored.


Kinetics and metabolism of amphetamine in the brain of rats of different ages. The kinetics and tissue distribution of amphetamine and its metabolites p-hydroxyamphetamine (p-PH-A) and p-hydroxynorephedrine (p-OH-NE) were investigated in young adult (3-4 months) and old (20-25 months) male rats, after i.p. injection of 5 mg/kg tritium labelled D-amphetamine. The concentrations of these drugs were determined in plasma, cerebral cortex, brainstem and hypothalamus, by thin layer chromatography. 1. From 60 min up to 4 hrs after injection of amphetamine the concentration of amphetamine in plasma and brain tissue of old rats was significantly (P less than 0.05 higher than in young adult animals. In both age groups the levels of amphetamine in cerebral cortex greater than brain stem greater than hypothalamus. 2. The blood-brain barrier is permutle to p-OH-A; 10 to 20 min afer i.v. injection of 10 muCi/kg of p-OH-A (10 mCi/m mole) the ratio of brain/blood plasma was found to be 1:3. The half life of p-OH-A in blood plasma was almost identical after injection of amphetamine and p-OH-A (90 min and 98 min respectively). 3. The levels of p-OH-NE in different brain areas were significantly lower (P less than 0.05) in old animals than in young adult rats 4 hrs after application of amphetamine. This metabolite of amphetamine shows a higher concentration in the hypothalamus earlier than in other brain regions.


Effects of reserpine and propranolol on anoxia-induced enzyme release from the isolated perfused guinea-pig-heart. The possibility of a protective effect by reserpine or propranolol on anoxia-induced released of malate and lactate dehydrogenase was investigated in isolated perfused hearts of guinea-pigs. After allowing 30 min of aerobic perfusion for the development of a steady state, the hearts from the nontreated group as well as the reserpine-pretreated or propranolol-treated group were subjected to a prolonged anoxia of 5 hrs. A marked enzyme release which occurred from the anoxic nontreated hearts was significantly inhibited by reserpine or propranolol. These findings suggest that the enzyme release from the anoxic myocardium is partly related to the liberation of endogenous catecholamines.


Norepinephrine release from nerve terminals within the rabbit superior cervical ganglion. Norepinephrine-3H (NE-3H) and its metabolic normetanephrine-3H were released from the superfused rabbit SCG incubated in tyrosine-3H in response to preganglionic stimulation. Neither dopamine-3H nor its metabolite, 3-methoxy-tyrosine could be detected in the superfusate from "control" or "nerve stimulated" tissues. Nerve stimulated NE-3H release a) was calcium dependent, b) had a stimulus threshold similar to that of C fibers, c) was not blocked by either 50 micromolar curare or 100 micromolar atropine, d) was abolished by chronic decentralization and e) was elicited by stimulation of both the cervical sympathetic and internal carotid nerves. These results suggest that there is a here-to-for undescribed, noradrenergic pathway which originates elsewhere in the sympathetic chain but terminates in the superior cervical ganglion.


Some physiological and pharmalogical characteristics of the stimulus induced release of norepinephrine from the rabbit superior cervical ganglion. The cervical sympathetic nerve stimulated release of norepinephrine (NE) from the rabbit superior cervical ganglion (SCG) was characterized. The quantity of NE released per impulse declined with increasing stimulation frequency over the range of 3/sec to 15/sec. Nerve stimulated NE release was potentiated by 1 micromolar desmethylimipramine and 25 micromolar phenoxylbenzamine and inhibited by 1 micromolar bretylium, 25 micromolar methoxamine and 1 micromolar prostaglandin E1. These results suggest that nerve stimulated NE release in the rabbit SCG occurs from sympathetic fibers which are subject to the same neurosecretory control mechanisms as sympathetic fibers elsewhere in the autonomic nervous system.


Oxygen uptake by suspension of mouse brain cells. A cell suspension was prepared by sieving mouse brain cortices in an isotonic  solution of purified polyvinylpyrrolidone. A large increase on the O2-uptake by the suspension could be obtained with the preparation procedure described. The respiratory rate of suspension, incubated in saline medium, containing 6.2 mM K+, 10 mM pyruvate, 5 mM fumarate and 0.9 mM 5'-AMP, was equal to 68% of the respiratory rate of slices. High K+ concentration (65 mM) stimulated O2-consumption of suspension by 64% (73% in slices).


Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. III. Analysis of amino acids after long-term potentiation. Following 30-min intermittent post-tetanic potentiation of monosynaptic reflexes in the ventral horn of the spinal cord of 10 cats, the amino acid composition was analyzed after reacting with 14C-dansylchloride and by two-dimensional chromatography. The amino acids in comparable segments of the spinal cord from eight animals after ether anesthesia and from five animals who were operated on but not stimulated were also analyzed. In the latter the operation itself influenced the amino acid composition as compared to those animals who were anesthetized. Comparison between the different control groups showed that the operated animals can be used as a control for calculation of the changes caused by potentiation. The amino acids glycine, glutamic acid and aspartic acid, which act as either inhibitory or excitatory neurotransmitters, increased significantly after potentiation, as did the amino acids lysine, histidine, leucine, isoleucine, and proline.


Brain lipids in pyridoxine-deficient young rats. Pyridoxine deficiency produced in rats during the period of development of the central nervous system resulted in a decreased incorporation of (1-14C) acetate into total lipid extracts of brain. It also resulted in a uniform decrease in the incorporation of the labeled precursor into the cholesterol, glycolipid and phospholipid fractions of brain. The specific radioactivity of purified cerebrosides and sulfatides was decreased by 78% in pyridoxine-deficient rats with respect to controls. The decreased incorporation of labeled precursor in the deficient rats was not due to the labeled precursor, since the specific radioactivity of brain acetate and the brain concentrations of acetyl coenzyme A and acetate were similar in both deficient and control rats. The results indicate that in pyridoxine deficiency established in the young rat there is an impaired formation of myelin.


Chloride compartments in embryonic brain tissue after intracerebral ouabain administration. The "chloride space" in brain tissue of 15- and 19-day-old chick embryos was studied during the 3 h following intracerebral administration of 3.4-10(-4) M ouabain. Total tissue water, dry substance, plasma and liquor and tissue chloride concentrations were determined. The chloride space in brain tissue was calculated on the basis of the brain-cerebrospinal fluid ratio and the brain-plasma ratio. The chloride concentration in blood plasma was generally unchanged after ouabain treatment. The chloride concentration in cerebrospinal fluid was lower in younger embryos during the whole 3-h period, whereas in 19-day-old embryos only during the 1st h. Tissue chloride concentration was generally elevated, but to a greater extent in younger embryos. Total brain tissue water increased for 3 h after ouabain treatment in 15-day-old embryos and for the first 2 h in 19-day-old embryos. The expansion of chloride space reached a new steady state during the 1st h after ouabain treatment and amounted to 12-15% of control values in 15-day-old embryos. The increase of chloride space in older embryos reached its maximum (14.8% of control values) within the 1st h and gradually decreased thereafter. The age-dependent changes of chloride compartmentation in embryonic brain tissue are discussed in relation to the previously investigated spongy state of the brain tissue in chick embryo.


Studies on the action of nerve growth factor. II. Neurotubule protein levels during neurite outgrowth. The neurotubule protein content of chick embryo 8-day dorsal root and 14-day sympathetic ganglia, induced to extend neurites in the presence of Nerve Growth Factor, was determined by the time-decay colchicine binding assay procedure and by two independent polyacrylamide gel electrophoresis systems. The initial level of neurotubule protein in dorsal root ganglia was approximately 16% of the total soluble protein. This value was constant during Nerve Growth Factor-mediated neurite outgrowth. The initial level of neurotubule protein in sympathetic ganglia was also approximately 16%, and was unchanged during neurite outgrowth. In addition, C1300 mouse neuroblastoma cells, induced to extend neurites in 0.1% serum, also did not exhibit a change in neurotubule protein concentration, which remained approximately 9% of the total soluble protein.


S100 on isolated neurons and glial cells from rat, rabbit and guinea pig during early postnatal development. The brain specific S100 protein has been demonstrated by immunofluorescence microscopy on neuronal cell membranes during postnatal development of rat, rabbit and guinea pig. S100 has been found in glial cell aggregates of rats 4-5 days old, of rabbits 2-3 days old, and of newborn guinea pig. The neuronal plasma membrane-bound portion of the protein appears later during development. In rats 10 to 12 days of age S100 could be found on one part of the cell membrane of Deiters' neurons and of Purkinje cells. In rats 12 to 15 days old cells from the cerebral cortex contained a heterogeneously distributed cell membrane-bound portion of S100. The protein on neuronal cell membranes could be seen somewhat earlier in rabbits as compared to rats. Newborn guinea pigs showed a heterogeneous distribution of the protein similar to that seen in adult animals. In rat and rabbit adults distribution and amounts of S100 were reached at days 25-30 and at days 20-24, respectively. The results obtained here are in agreement with biochemical results. Our findings suggest that the membrane-bound part of the S100 protein with its heterogeneous and polar distribution on the nerve cell plasma membranes (demonstratable in parallel with physical and behavioral maturation of the animals) is a sign of a protein differentiation of the neuron.


[Needle therapy in neurology].

[Needle therapy in neurology]. The term "needle treatment" has been used by the author for designation of all analgetic procedures in which the skin receptors are stimulated by insertion of needles. Acupuncture and its modification proposed by the author fall into this category. In the new method needles are inserted into painful points and 0.1-0.2 ml of 10% sodium chloride solution is injected. The method is used for treatment of pain in ischalgia, facial neuralgia and shoulder pains and in refractory, so-called idiopathic headaches. The author describes three neural mechanisms participating in pain inhibition by means of peripheral receptor stimulation.


[Sural nerve phospholipids in some genetically determined nervous system diseases]. Phospholipid fraction pattern was determined in sural nerve in cases of suspected storage diseases. The material was obtained by means fo biopsy from 22 patients. In some patients features of polyneuropathy were found. Normal values of phospholipids were determined in 22 dying patients who had to neurological diseases. The most frequently observed change concerning the biochemical composition of the sural nerve in this material was a fall in the total amount of phosphatidyl ethanolamine (cephalin) and appearance of lysolecithins which are normally absent. In attempted correlation of histological and biochemical findings in the sural nerve with clinical signs of polyneuropathy it was observed that biochemical changes were present in cases without clinical evidence of polyneuropathy. Biochemical as well as histological investigations of sural nerve may help in intravital diagnosis of diseases belonging to the group of thesauroses.


[Development of righting reflexes and their influence on the development of static functions in children with infantile cerebral palsy]. In a group of 55 children with signs of central nervous system lesions the development of righting reflexes and static functions was observed during the first 3 years of life. A delay and disturbances in the development of righting reflexes and static functions was observed with differences between the individual groups of infantile cerebral palsy.


[Catalase-like activity in cerebrospinal fluid in patients with cerebral stroke]. Catalase-like activity was determined in the cerebrospinal fluid of 16 patients with cerebral haemorrhage, 24 cases od encephalomalacia due to thrombosis, and 10 controls. It was demonstrated that catalase-like activity in the cerebrospinal fluid of patients with cerebral stroke is significantly raised in relation to the activity observed in controls. This rise is patricularly evident in the first 24 hours after the onset. The rise was statistically significant only in the group of encephalomalacia.


[Conduction velocity in peripheral nerves in healthy and sick children]. Conduction velocity was determined in motor fibres of peripheral nerves in healthy children aged from 4 months to 15 years and in children with spinal muscular atrophy, untreated phenylketonuria, myopathies and infantile cerebral palsy. Conduction velocity equalling that in adults is reached in the ulnar and peroneal nerves at the age of about 3 years, in the median nerve somewhat later (at the age of 4-5 years). In cases of untreated phenylketonuria, myopathies and infantile cerebral palsy conduction velocity was about normal. In spinal muscular atrophy decreased conduction velocity in the youngest children may indicate delayed myelination of peripheral nerves.


[Familial occurrence of Crouzon's disease]. The authors report a family of 8 subjects in which 6 members demonstrate significant abnormalities in the development of the facial skeleton and the skull in the form of craniofacial dysostosis (Crouzon's disease) with complications including optic nerve atrophy, divergent squint in 4 children and borderline mental retardation in 3 of these children.


[Epidemic of lymphocytic cerebrospinal meningitis in the fall of 1974 at Grudziadz]. In 1974 an epidemic of lymphocytic cerebrospinal meningitis occurred in the Province of Bydgoszcz. Thirty-nine cases of this disease were hospitalized at the neurological department of the hospital in Grudziadz. Virological investigations demonstrated presence of Coxsackie A9 virus. The manifestations of the disease, diagnostic methods and treatment are described.


[System of rapid automatic digital recording of cerebrospinal fluid pressure]. The authors describe a system for rapid digital automatic recording of cerebrospinal fluid pressure. The results are recorded in numerical form by a recorder. Owing to this quantitative expression of results the subjective evaluation of analog curves is avoided. The system may be used also to measure other slowly changing physiological processes.


[Angiomas of blood vessels supplying the basal ganglia and the diencephalon]. The author discusses the problem of surgical treatment of intracranial angiomas situated in basal ganglia and diencephalon. Vascular malformations in this area were found in 7.5% of cases in a group of 80 patients with intracranial angiomas. In all 6 cases the onset of the disease was sudden with meningocerebral haemorrhage, prolonged coma and hemiplegia. The malformations had usually the features of arteriovenous angioma. The afferent vessels come usually from the medial short and long vessels branching off from the anterior and middle cerebral arteries, the choroid arteries and the posterior communicating artery. The author isolated two types of malformations differing in their situation, shape and range of vascularization. In the "subventricular" type situated within the nucleus caudatus and lenticularis, internal capsule and thalamus the malformation can be exposed well from the approach through the lateral ventricle. The angiomas situated nearer to the base of hemisphere (the parabasal type), in the diencephalon, in the area of the olfactory triangle, substantia perforata anterior and even crus cerebri can be exposed best using the subfrontal approach. The author believes that in many cases of these malformations regarded usually as inoperable, radical operation can be done with selective removal of angioma by means of microsurgery. This procedure was applied in 2 cases (Fig. 2 and 3).


[Case of multiple sclerosis with Devic's syndrome and secondary cerebellar signs]. The authors describe a 43-year-old woman treated for multiple sclerosis during 11 years in whom at the end of her life tetraplegia, bulbar syndrome and cerebellar syndrome developed. Postmortem examination of the brain disclosed changes compatible with the diagnosis of multiple sclerosis, diffuse sclerosis and neuromyelitis optica. The variability of the demyelinating process is discussed. In this case this variability was responsible for successive appearance of various nosological entities depending on the "balance of power" between the factors damaging myelin and the resistance of the organism.


[Comparison of the bronchodilator action of fenoterol and salbutamol by aerosol administration in patients with bronchial asthma]. A comparison was made between the bronchodilatatory activity of phenoterol (hydroxyphenylorciprenaline) and salbutamol in patients with bronchial asthma. The results showed that both drugs had marked activity at therapeutic doses, though phenoterol was more rapid (within 10 min of inhalation) and more longlasting (up to 6-7 hr). Its loss of therapeutic effect was also slower than that of hitherto experimented drugs.


[Case of Behcet's disease].

[Case of Behcet's disease]. The author reports a case of Behçet's disease in a 45-year-old man with eye lesions, changes on the skin and in the nervous system with inflammatory changes in the cerebrospinal fluid. The course of the disease was chronic, with periodic exacerbations. Steroid treatment gave good results.


[Antihypertensive activity of a new molecule, 2,6-dichloro-benzylidene aminoguanidine acetate]. The anti-hypertensive action of 2,6-dichlorobenzylideneaminoguanidine acetate (BR 750) is described. Inter-patient comparison pointed out its excellent tolerance, together with an anti-hypertensive activity at least equal to that of alpha-methyldopa.


[Origin of oncogenic viruses].

[Origin of oncogenic viruses]. On the basis of the literature, and particularly of recent paraprocessing studies, the possible origin of oncogenous RNA viruses in human is discussed. The concept of the irritative theory as the origin of most such viruses, according to the "wandering gene" concept, is reiterated.


[Epileptic seizures in children caused by developmental anomalies of meningocerebral vessels]. In the light of pertinent literature the authors discuss two interesting cases of developmental anomalies of cerebral vessels demonstrated by means of angiography which were the cause of epileptic seizures and progressive dementia.


Immune responses to infections with coccidia in chickens: gut hypersensitivity. Sporulated oocysts or oocyst hulls of Eimeria acervulina given via the crop, and oocyst juice or sporozoites inoculated directly into the intestinal lumen, were tested for their effects on the hypersensitivity of the intestines of immunized and susceptible birds. Only viable sporozoites consistently caused an increase in the permeability of the immunized intestine to macromolecules, shown by the leakage of intravenously injected dye. Repulsion of epithelium and disruption of the villi were seen more often in immunized than in susceptible chickens but there was no correlation with treatment or with dye leakage. The hypersensitive response of immune intestines challenged with a heterologous organism was approximately half as intense as the response to homologous challenge. The significance of these findings in relation to immunity to coccidiosis is discussed.


Enzyme variation in Eimeria species of the chicken. A method for the biochemical identification of protozoa belonging to the genus Eimeria is described for the first time. Starch gel electrophoresis of the enzymes lactate dehydrogenase, glucose phosphate isomerase, 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase from parasite extracts revealed both intra- and inter-species differences when 11 strains representative of 6 species of Eimeria were examined. Oocysts were the most accessible parasite stage for investigation but sporozoites and merozoites of an embryo-adapted strain of E. tenella were also examined for enzyme activity.


Genetic control of immune responses to parasites: selection for responsiveness and non-responsiveness to Trichuris muris in random-bred mice. Populations of Schofield strain, random-bred mice were shown to have a bimodal variation in ability to bring about immune expulsion of the nematode Trichuris muris. This variation was genetically determined and independent of the size of infection experienced. The proportion of mice unable to achieve worm expulsion (non-responders) was relatively constant in various populations of the strain but was increased by selective breeding from mice of known status. Crosses made between non-responder and responder mice produced progeny that were almost all (92%) of responder phenotype, showing that the ability to achieve worm expulsion was inherited as a dominant characteristic. It is suggested that the genetic control involves a small number of genes; the possible immunological mechanisms by which control is mediated are briefly discussed.


Structure and invasive behaviour of Plasmodium knowlesi merozoites in vitro. The structure and invasive behaviour of extracellular erythrocytic merozoites prepared by a cell sieving method have been studied with the electron microscope. Free merozoites contain organelles similar to those described in late schizonts of Plasmodium knowlesi. Their surface is lined by a coat of short filaments. On mixing with fresh red cells, merozoites at first adhere, then cause the red cell surface to invaginate rapidly, often with the formation of narrow membranous channels in the red cell interior. As the merozoite enters the invagination it forms an attachment by its cell coat to the rim of the pit, and finally leaves this coat behind as it is enclosed in a red cell vacuole. Dense, rounded intracellular bodies then move to the merozoite periphery, and apparently rupture to cause further localized invagination of the red cell vacuole. The merozoite finally loses its rhoptries, the pellicle is reduced to a single membrane and the parasite becomes a trophozoite. Invasion is complete by 1 min after adhesion, and the trophozoite is formed by 10 min.


An experimental investigation of a direct life-cycle in Reighardia sternae (Diesing, 1864), a pentastomid parasite of the herring gull (Larus argentatus). A direct life-cycle in Reighardia sternae, a cephalobaenid pentastomid of gulls was investigated: the work was prompted by a report of eggs and larvae recovered from the stomach and intestine of a naturally infected gull. Infective pentastomid eggs were obtained by surgically transplanting maturing female Reighardia, taken from freshly shot wild gulls, into captive recipients. Faecal material from birds thus artificially infected was collected daily and examined for eggs. Eggs were force fed to 33 hand-reared (from eggs or nestlings) juvenile gulls which were selected at random and sacrificed at intervals thereafter and examined for pentastomids. One hour after infection, primary larvae appear in the body cavity where they moult immediately. They grow steadily and by 27-35 days are sexually differentiated, and by 66 days have copulated. Fertilized females take a further 116 days to produce eggs by which time they are 7-6 cm long. The complex migrations undertaken by developing larvae in the gull, and the problems of the mechanism of direct transmission, are discussed.


Observations on the development of Haemonchus contortus in young sheep given a single infection. Worm free lambs 2-4 months old were given a single infection of 50,000 Haemonchus contortus larvae. The changes in packed red cell volume were compared with those of uninfected sheep and the infected sheep were divided into two groups according to the rate of change of packed cell volume. In group 1, packed cell volume fell sharply from the 10th day of infection and the sheep eventually died. In group 2, the fall was less marked and the packed cell volume returned to normal after about 40 days. The rates of increase of parasite body length and dry weight were compared for the two groups. Parasites in group 1 sheep grew more slowly than their group 2 contemporaries. Accurate planning of metabolic studies on H. contortus was made possible by using this information to predict the course of an infection and the size of the worms. Parasite development was also measured in sheep for which the packed cell volume was not recorded. Computer analysis showed that adult worm length increase did not follow a simple growth pattern starting from the last ecdysis, but consisted of a rapid elongation followed by a simple negative exponential increase. Dry weight increase also followed a negative exponential during the second phase. Measurements of dry weight as a percentage of wet weight indicated that the rapid elongation was possibly linked with cell enlargement by the uptake of water.


Some influences of population density on Hymenolepis diminuta in rats. When measured 56 days postinfection the length, wet weight and dry weight of Hymenolepis diminuta were all found to decrease with increasing number of cysticercoids given up to 20. The mean position of the worms in 10, 12 and 20 worm infections is significantly posterior to that of 1, 2 and 5 worm infections and the worms are attached over a wider area of the intestine. Egg production by the worms was followed up to day 56 postinfection; the number of eggs produced per worm and even per rat decreased with increasing population density. Thus the best way to get most eggs and to maintain the parasite in the laboratory is to have rats infected with only one tapeworm. Rats given 1-20 cysticercoids showed a mean recovery of 100-65%, while rats given 40-200 cysticercoids showed a mean recovery ranging from 13 to 2%. In addition to 'normal' worms, defined as worms greater than 10 mm, small, most probably destrobilated, worms were found. In the 50 and 100 cysticercoid infections, worm recoveries were, respectively, 8% 'normal', 16% small, and 2% 'normal', 5% small. From the significantly lower recovery from heavy infections it is concluded that a deleterious factor is operating during the 8 weeks after the infection.


Possible immunological damage to the tegument of Hymenolepis diminuta in mice and rats. Opaque or darkened areas (DA) of variable size and position occur on Hymenolepis diminuta in mice and rats. In mice DA normally first appear in the neck region of the worm but subsequently they appear elsewhere and increase in number until destrobilation or worm expulsion. The posterior of destrobilated worms is often darkened. In the more immunogenic infections with six cysticercoids there are more DA per worm than in infections with one cysticercoid. DA are areas of the tegument with a homogeneous increase in electron density; abnormal mitochondria; reduced granular endoplasmic reticulum, Golgi complexes and discoidal secretory bodies; and accumulation of lipid droplets. DA disappear from worms maintained for up to 4 h in Hanks' balanced salt solution and can be induced by mechanical damage to the worms. As the numbers of DA increase with the duration and intensity of infection and have similarities with types of cell injury, they are probably sites of worm pathology induced by host immunity.


Increased lysosomal hydrolase activity in kidney and brain from the vitamin B6-deficient developing rat. Between 7 and 9 postnatal days, the kidney, spleen heart, and liver from vitamin B6-deficient young either plateaued and failed to gain weight or lost weight, whereas brain continued to gain weight but at a more reduced rate than normal. The level of cofactor in kidney of experimental animals was below that of controls at all time points studied. alpha-L-Fucosidase activity was already moderately increased in deficient kidney at 3 postnatal days and remained elevated throughout the time course. beta-D-galactosidase, acid phosphatase, and hexosaminidases A and B in vitamin B6-deficient young all showed moderate increases in activities after 9 days, at one or more time points. In brain, alpha-L-fucosidase activity was increased somewhat throughout the time course, but changes in beta-D-glucuronidase, beta-D-galactosidase, alpha-D-mannosidase, acid phosphatase, and hexosaminidases A and B did not occur until after 7 postnatal days. When weights of kidney and brain were both normal, there was a marked elevation in alpha-L-fucosidase activity in these organs suggesting that this increase in enzyme activity may be a specific effect of vitamin B6 deficiency. Elevated alpha-L-fucosidase activity in kidhney may reflect alterations in fucose-containing glycosubstances of glomerular basement membranes.


The bilirubin-induced photodegradation of deoxyribonucleic acid. The widespread use of phototherapy for neonatal jaundice has caused some concern since little is known about the cellular consequences of such treatment. The present study was undertaken to determine the effects of photoactivated bilirubin on the structure of purified deoxyribonucleic acid. DNA illuminated in the presence of bilirubin exhibited altered physical chemical properties as evidence by (1) a changed thermal helix coil transition profile, (2) a sensitivity of the treated DNA to alkaline degradation, and (3) a limited depolymerization of single-stranded DNA. The above changes were observed with a total light dosage representing only 5% of that received by a newborn infant during a 24-hr period of phototherapy in our nursery. In view of the known relationship between ability to modify cellular DNA and mutagenic and/or carcinogenic potential, the present results suggest that phototherapy is a complex process which may have potentially dangerous sequelae.


Maple syrup urine disease: analysis of branched chain ketoacid decarboxylation in cultured fibroblasts. Kinetic data are presented for the decarboxylation of branched chain alpha-ketoacids (BCKA) by intact human fibroblasts. Cultured cells of normal individuals and nine patients with different clinical pictures of maple syrup urine disease (MSUD) are studied with both alpha-ketoisocaproic acid (2-oxo-4-methylpentanoic acid (KIC)) and alpha-ketoisovaleric acid (2-oxo-3-methylbutanoic acid (KIVA)) as substrates. One normal cell strain and one patient cell strain is analyzed with alpha-keto-beta-methyl-n-valeric acid (2-oxo-3-methylpentanoic acid (MEVA)) as a substrate. A biphasic degradation kinetic for each BCKA is obtained for normal control subjects. The component with higher substrate affinity is affected in MSUD: for KIC the normally hyperbolic substrate curve is changed to sigmoid shape, for KIVA and MEVA as substrates this component is not detectable at all. Considering qualitative aspects of the BCKA decarboxylation kinetics intact fibroblasts yield the same results as our recent studies with the decarboxylase moieties of partially purified kidney BCKA dehydrogenase of normal individuals and one patient with classic MSUD (27). The decarboxylation velocities for normal and patient fibroblasts with one exception differ widely at low but not at high substrate concentrations of BCKA. To get meaningful data on the residual substrate degradation activities with intact fibroblasts of different phenotypes of MSUD physiologically low substrate concentrations are required in the assay.


Polyamines in cystic fibrosis.

Polyamines in cystic fibrosis. Polyamine concentrations have been measured in blood samples from a series of cystic fibrosis (CF) patients and control subjects. Analyses were made by a fluorometric method, in which the amines were reacted with dansyl chloride and separated by thin layer chromatography on Kieselguhr. There was no significant difference between the polyamine concentrations of blood samples from CF patients and control subjects. Also, the spermidine-spermine ratio was similar in both groups. Polyamines were also analyzed in exocrine fluids, and although none could be detected in either CF or control sweat or saliva, significant amounts of spermine and spermidine were present in all samples of bile and duodenal fluids. It thus seems likely that the biliary route is a significant pathway in the human for excretion of polyamines. The observation that polyamines are excreted in considerable concentrations via the bile in children may be of interest in view of the reports of elevated urinary polyamine concentrations in neoplastic states. Since measurable amounts of spermine and spermidine were detected in all six bile preparations available for this study, analysis of these substances in bile may be of benefit in particular cases.


Periluminal antigen in fetal kidneys.

Periluminal antigen in fetal kidneys. Eighty-nine kidneys obtained from human fetuses, 6-31 weeks of gestational age, were studied for the presence of apical periluminal antigen. Sera of rats in which nephrotic renal disease had been produced and which were known to contain considerable amounts of periluminal antibodies were used. Of the less than 12-week-old fetal kidneys, 24% showed the presence of periluminal antigen and this value increased (up to 100%) in older fetuses. It is believed that this observation favors the concept that this antigen is synthesized in proximal tubular cells rather than reabsorbed into them. This supports the concept that the experimental model is an endogenous complex disease. In accordance with these results, the disease incidence, using human fetal kidneys and kidneys obtained from newborn rats, was 60% and 62%, respectively.


Deficiency of arginine esterase in cystic fibrosis of the pancreas: demonstration of the proteolytic nature of the activity. Proteolytic activity, defined as the hydrolysis of peptide bonds involving the carboxyl group of L-arginine, in plasma of patients with cystic fibrosis, heterozygotes, and control subjects has been assayed using a fluorometric method with protamine as the substrate and fluorescamine as the reagent. The mean total proteolytic activity in plasma of patients with cystic fibrosis was approximately one-half the mean total activity in control subjects and heterozygotes. The mean proteolytic activity inhibited by soybean trypsin inhibitor in plasma of patients with cystic fibrosis was approximately one-third that of control subjects and heterozygotes. The relationship of arginine esterase activity to proteolytic activity was investigated. The pH optimum and action of reversible and irreversible inhibitors were similar for both activites, suggesting that the arginine esterase activity and proteolytic activity represent similar catalytic entities. These findings are consistent with our hypothesis that the basic defect in cystic fibrosis may reside in the deficieny of a proteolytic enzyme which results in the accumulation of the various cationic macromolecular "factors" described by other investigators in serum of patients with cystic fibrosis. The demonstration of a deficiency of proteolytic activity as assayed by the hydrolysis of protamine, a cationic polypeptide, could explain the presence of ciliotoxic cationic protein or polypeptide factors in serum of patients with cystic fibrosis and may, in some unknown manner, be related to the clinical manifestations of the disease.


Effect of adrenergic blockade on glucagon and growth hormone secretion in normal and diabetic children. Studies were conducted in four normal and six diabetic children to assess the role of adrenergic blockade on basal and arginine-stimulated growth hormone and glucagon secreation. Each subject had, on three separate occasions, infusion of arginine alone or in conjunction with alpha (phentolamine) or beta (propranolol) adrenergic blockade. Clinically, there was evidence of adequate blockade by each agent. Basal hormone growth levels were not significantly different in the two groups (1.3 +/- 0.2 to 2.1 +/- 1.0 ng/ml in normal subjects; 3.0 +/- 1.1 to 6.0 +/- 3.1 ng/ml in diabetics (mean +/- 1 SEM)) but the peak growth hormone after arginine was significantly greater in the diabetic children than control subjects (34.3 +/- 7.2 versus 12.3 +/- 3.1); in both groups alpha-blockade suppressed the growth hormone response, whereas beta-blockade had no significant effect. Basal glucagon concentrations were similar in both groups (147 +/- 31 to 214 +/- 21 pg/ml in normal subjects; 100 +/- 20 to 124 +/- 17 pg/ml in diabetics on three different occasions) despite the coexistent hyperglycemia of the diabetics. Neither basal nor maximally stimulated glucagon secretion was significantly affected by alpha or beta blockade in the juvenile diabetic or control children. The results suggest that sympathetic overactivity via alpha receptors may contribute to the hypersecretion of growth hormone in juvenile diabetes and that the alpha or beta adrenergic receptor alone does not appear to modulate basal or arginine stimulated glucagon secretion.


[Diagnosis of left auricular myxomas by echocardiography. 2 cases]. The echocardiograms of two patients with a myxoma of the left atrium are presented. In each case there was an abnormal echo mass visible in diastole behind the greater mitral cusp. In addition, in one case, the mass was seen in the left atrium in tricuspid and aortic projection. The diagnosis was not suspected clinically and it was the ultrasound examination, carried out on a routine basis, which led to its discovery. This noninvasive technique is thus a valuable study in the demonstration of myxomas of the left atrium.


[The blood chloride-phosphorus ratio in the diagnosis of hyperparathyroidism. 31 parathyroid adenomas]. The authors relate their experience in the study of chloremia, phosphatemia and their relationship in the diagnosis of parathormonal hypersecretion states, 31 cases of parathyroid adenoma are compared to 26 cases of hypercalcemia depending on other mechanisms. The studied relationship appears to be interesting in the diagnostic work-up of parathyroid adenoma as well as in appreciating the mechanism of hypercalcemia during the course of other neoplastic disorders.


[Cerebral infarctions. Study of their prevention]. 1) In 113 patients with cerebral infarction, the cause of infarction was cardiac embolism in 35, atherosclerotic thromboembolism in 45. It was either cardiac embolism or atherosclerosis but undetermined in 30. 2) Seven risk factors have been analysed. Eight patients (7 p.cent) had none of these factors. In the 105 remaining patients risk factors were: a) atrial fibrillation in 36, diagnosed in 21. Efficient treatment was applied in 1 or perhaps in 2 patients; b) High blood pressure in 39, diagnosed in 32, efficiently treated in 5; c) dyslipidemia in 42, diagnosed in 9, efficiently treated in 3; d) obesity in 50, efficiently tackled in 2; e) diabetes in 24, diagnosed in 11, efficiently treated in 2; f) hyperuricemia in 28, diagnosed in 1 with no efficient treatment; g) smoking in 44, abandonned by 1 only. 3) The high frequency of cardiac embolism is briefly commented. 4) Non diagnosis or unefficient treatment was present in a high proportion of cases. Realizing this regrettable state of affairs should result in better preventive diagnosis and treatment which, is assumed, could significantly reduce cerebral infarction.


[Operated primary bronchial cancer. Study of the survival of 560 patients]. 560 patients with primary broncho-pulmonary carcinoma underwent surgery, excision being possible in 78 p. cent. Overall post-operative survival is 29 p. cent at 5 years and 11.5 p. cent at ten years. Among the various prognostic factors, lymph node involvement is the most important. In the most favourable cases, survival at 5 years is 46 p. cent. Such a result shows that the prognosis in primary carcinoma of the lung is not as grim as it is usually said to be.


[Labile arterial hypertension. Hemodynamic study with measurement of renin activity]. Plasma renin activity (PRA) was increased and highly sensitive to stimulation in eight cases of labile hypertension (HT), which were also studied haemodynamically. This increase in PRA would appear to result from neuro-adrenergic hyperactivity. The haemodynamic were characterised by a diversity which may be explained on the basis of differentiated sympathetic hyperactivity: exclusive or predominant beta-adrenergic activity causing a hyperkinetic cardiac state with moderate HT adapted to the increased cardiac output; A simultaneous alpha- and beta-adrenergic activity resulting in cardiac hyperkinesis with a relative or potential increase in peripheral resistance; isolated or predominant alpha-adrenergic hyperactivity causing a potential increase in peripheral resistance revealed or increased by effort, in the presence of a normal cardiac output. In certain cases of labile HT however, despite an increased PRA, haemodynamic findings were normal at rest and with effort, at the time of catheterisation.


[Aortic ruptures in traffic accident traumatology]. 8 cases of rupture of the aorta seen in a series of 62 autopsies were studied in the context of a multidisciplinary enquiry into road accidents. In the light of these cases, the literature and experimental findings, different mechanisms are described, an essential step in the prevention of this lesion which is the main cause of death in 15 p. cent of cases.


The treatment of urinary tract infection. Urinary infections are due to organisms gaining entry from the genital area and are therefore much commoner in females than in males. In male patients of any age urinary infection is often associated with some underlying abnormality and warrants full investigation. Recurrent infections in girl children may lead to renal scarring and later impairment of function and require careful management. Occult infections occur. The majority of patients with urinary symptoms are adult women, and symptoms tend to recur. These can produce great distress but in this age-group they do not lead to renal scarring. When symptoms occur for the first time during pregnancy they are associated with a high prevalence of underlying radiological abnormalities and should be investigated after the pregnancy. Care should be taken to ensure that apparent uprinary symptoms due to other causes are not mistakenly treated with antibiotics. The immediate management of patients with urinary symptoms consists in relief of discomfort, combined with treatment by an antibacterial drug appropriate for the infecting organism. The urine culture should be repeated after the course of treatment. Simple measures can prevent or reduce recurrences in adult women.


The management of pregnancy in diabetes mellitus. A personal series of 100 consecutive diabetic pregnancies of over 28 weeks' gestation in 78 mothers during the period from January 1961 to June 1973, is described. There were 92 live births (including two pairs of twins) and 10 foetal deaths (9.8 per cent). The findings show that in diabetic pregnancies good results can be obtained by meticulous control and carefully coordinated obstetric and paediatric care.


Failures in the management of congenital hip displacement in the newborn. Congenital hip displacement in the newborn presents in two forms: (1) Those babies in whom the capsule of the hip-joint is mechanically stretched. Spontaneous reduction and recovery is high in this group, if the babies are nursed in the prone posture with double nappies (Fig 5). (2) One in a thousand babies is born with infolding of the posterior capsule and secondary contracture of the anterior capsule. This soft tissue deformation occurs in varying degrees, but it frequently prevents spontaneous reduction. Most of these cases are missed and present as infantile congenital hip displacements, when the child is 12-18 months old. In those who are unfortunate enough to be detected and treated conservatively, in the first year of life, there is a high risk of iatrogenic bony deformation. For, as in talipes equinovarus, the bony components of the neonatal hip-joint are more susceptible to mechanical compression than the soft tissue structures.


Haematoporphyrins in the diagnosis and treatment of carcinoma of the bladder. The localization of an haematoporphyrin derivative (HpD) was studied in the operative specimens of three patients with carcinoma of the bladder. The drug was found to localize preferentially in malignant and premalignant mucosa and not in normal bladder tissues. It is suggested that HpD fluorescence might be useful as a diagnostic aid and its photosensitizing properties be used as a mode of therapy for carcinoma of the bladder.


An approach to the surveying of radiation environments for radiation protection purposes. Many of the inadequacies of the system presently used for surveying environments containing penetrating radiation stem from the impossibility of defining a radiation parameter which is additive, measurable and closely related to peak dose equivalent in the body. Many of the present conceptual difficulties would be eliminated if surveys were made in terms of a quantity 'dose equivalent ceiling' defined as the sum of the peak dose equivalents generated by all the components of the field if each were incident normally to the front face of an anthropomorphic phantom. 'Dose equivalent ceiling' is close to the quantity measured by existing instruments, is both additive and measurable, and can be rigorously related to primary radiation field quantities. It is always greater than peak dose equivalent in the body, and would be used to define an exposure period during which a given dose equivalent could not be exceeded. The dose to specific parts of the person's body would then be estimated by personal dosimetry. Fields of low penetrating radiation could continue to be surveyed in terms of dose to specific superficial organs. Dose equivalent ceiling, which corresponds to the instrumental measurement, exceeds dose equivalent index, an indication of peak dose equivalent in the body, by a factor which can be as large as six.


Study of contrast and modulation mechanisms in X-ray/photon transverse axial transmission tomography. The ultimate capabibity and a detailed study of contrast and modulation in the context of photon transmission tomography (or computerized transverse axial tomography (CTAT)) is presented. Quantitative evaluation of atomic number, density and electron density of compound materials were made by X-ray fluorescence and combustion analysis, and the attenuation coefficients of photoelectric and Compton effect were measured with high resolution Ge(Li) and Si(Li) detectors. This study provides a guide to an understanding of the high resolution of the currently existing X-ray transmission CTAT scanner (EMI scanner) and to the future development of high resolution scanners.


Spectra and dosimetry related to neutron irradiations of the human body. Neutron spectra at various locations in a phantom, irradiated by collimated beams of 14 MeV neutrons and neutrons from 252 Cf and Po-Be sources, were calculated using the Monte Carlo technique. These spectra give an indication of the distortion in source spectra associated with neutron irradiations of the body for therapeutic and diagnostic purposes. The effect of the spectral distortions on the dose response of several activation and damage track detectors was investigated. Of the dosemeters studied, Np has a dose response most nearly independent (+/-10%) of the spectral changes.


An approach to microdosimetry in a pi- meson beam using nuclear emulsions. K5 emulsions 10 mum thick were exposed at various depths in a perspex phantom to a 70 MeV pi- meson beam and counts taken of the tracks in emulsion volumes 7x7x10 mum3. Data are presented on the number of track events and also the total number of grains associated with each event in each of four categories spanning the LET range of the secondary particles. The number of heavy tracks (category 4) shows an increased incidence in the region of the stopping pi- mesons (14-5 cm in perspex) while the number of single grains (category 1) decreases with depth. Categories 2 and 3 (grain clusters and light tracks) are approximately constant with depth. An estimate of the grain sensitivity is obtained by taking the proton as representative of the whole range of secondary particles. This procedure gives a value of 5 keV per grain in the pi- peak. The LET of light tracks was therefore in the range 1-10 keV mum-1 in emulsion, scaling to 0-4-4 keV mum-1 in water. Heavy tracks have LET values in excess of 4 keV mum-1 in water.


Cross-sections for the inactivation of ribonuclease by slow heavy ions. Average cross-sections for inactivation of dry ribonuclease by H, He and N projectiles with energies between 100 eV and 10 keV are presented. The trend of the damage cross-sections with particle energy is consistent with the trend of the molecular quasi-elastic scattering and ionization cross-sections. A tentative radiation damage model is proposed in which single hit damage attributed to direct physical interactions by the primary and secondary radiations is supplemented by chemical action of the elastically scattered knock-on atoms which inactivate additional targets with an efficiency of 50-100%. Further experiments at energies below 100 eV are required for positive confirmation of the chemical efficiency. Free electrons (sub-ionizing) are chemically relatively innocuous (less than 10% efficiency). Saturation effects are satisfactorily accounted for in this model. Inactivation penetration depths measured in the microcrystalline enzyme agree with the theoretical predictions if a residual range of about 8 mug cm-2 is included. The mean energy expenditure to produce inactivation of a ribonuclease molecule is found to vary from 30 eV for 100 eV protons to 220 eV He and N ions.


Hit cross-sections in single target theory. A theoretical single target, single or multi-hit model for the biological effect cross-section for charged particles and gamma rays is expressed in terms of the fundamental physical interaction cross-sections. The model allows for the chemical action of the fragments and includes correction for saturation effects. An interesting conclusion, based on very limited experimental evidence, is that there are prospects of constructing a new system of radiation dosimetry with only two significant parameters; the effective volume of the target and the concentration of events. No energy parameters are necessary.


Experimental determination of W for oxygen ions in nitrogen. 'Differential' and integral measurements were made of the W value (average energy required to form an ion pair) for oxygen ions in nitrogen gas. A variable pressure cylindrical ionization chamber with a differential pumping section was employed. The average energy deposited per particle in the chamber was determined by integrating the energy spectrum measured with a heavy ion solid state detector. In the integral measurement of W, the particle was completely stopped in the chamber and the total ionization produced in the chamber was measured. The integral W value for 34-5 MeV oxygen ions was found to be 38-6 +/- 0-54 eV per ion pair. For 'differential' measurements, the pressure in the chamber was raised to 0-003, 1, 5, 15 and 20 Torr; and measurements of ionization currents and average energy deposited per particle were made at each pressure. From differences between these measurements 'differential' W was found. The average value of fifteen 'differential' W values was found to be 38-6 +/- 1-16 eV per ion pair.


Secondary radiation from a spherical tissue-equivalent phantom irradiated with 60Co gamma radiation and 6 MV X-rays. The angular dependence and the dependence on the phantom mass of the secondary exposure rate from spherical tissue-equivalent phantoms irradiated with 60Co gamma radiation and 6 MV X-rays have been investigated both by measurement and by calculation using the Monte Carlo method and approximate methods. A nonlinear dependence on the phantom mass was found. Calculation of the differential photon fluence was also made. These measurements and calculations can be used when calculating the required barrier thickness for walls which are not hit by primary radiation.


Experimental X-ray attenuation coefficients at low photon energies for substances of medical importance. Recent experimental values of X-ray mass attenuation coefficients for the elements zota = 6 to zota = 18 in the energy range from 4 to 25 keV suggest improvements to the data set presented in the ICRU Report 17. The results are, however, in excellent agreement with the theoretical data of Storm and Israel (1970). Values of mass attenuation coefficient for these elements and for a selection of materials of medical and biological importance are presented.


Rapid depth dose determination by a computer-controlled dosimetry system. A comprehensive depth dose measuring system controlled by a small computer has been designed to enable full depth dose information for a linear accelerator to be obtained within one day. An ionization microchamber is moved rapidly under computer control in a horizontal plane to preselected points within a water phantom by two stepping motors to a spatial resolution of 0-025 mm. The ionization current pulses are converted to DC voltages by an interface providing complete charge integration and yet having a rapid response to drastic changes in dose level. These are fed to the computer for analysis and subsequent conversion to depth dose data. The chamber path follows a preselected fan-shaped grid after automatic determination of the X-ray beam central axis. The combination of rapid chamber motion with halts for charge integration and computer sampling has resulted in fast data acquisition independent of measurement response times. This information, which is stored on disc, can be directly read by a treatment planning program. The overall accuracy of measurement lies within 0-5% of the true depth dose at any point. Central axis and transverse profiles can be assessed at the time of measurement through visualization on the computer storage oscilloscope.


Ion distributions in plane and cylindrical chambers. The ion chamber equations of Thomson include both ion recombination and space-charge terms. Neglecting the space-charge term, an exact solution is obtained for the ion densities across a plane ionization chamber. The method is extended to the cylindrical chamber, and examples are given of the expected ion distributions in both geometries. Current-voltage relationships are derived for both chambers and compared with those of other workers. If the space-charge term is retained, the ion chamber equations for both geometries are not soluble in closed form. The cylindrical chamber is considered and a computer solution is obtained for the ion distributions and current. Comparison with the nonspace-charge solution shows that while there is only a small difference in the current-voltage relationship, a significant difference can occur in the ion concentrations.


[Prevention of venous thrombosis in surgery. Very brief advice]. Avoid immobilization before and immediately after the operation : do not rely simply on raising of the legs but ensure that the patient walks as soon as po-sible. Apply elastic support bandages to the lower limbs before, during, and after the operation. Limit the duration of the operation and of the general anaesthesia. Reduce trauma of the vessels to a minimum during the operation. Give aspirin before and after the operation : 3 X 0,50 g.


[General practitioner's approach to deep phlebitides of the leg]. The approach of a general practitioner to deep phlebitis of the lower limbs.


[Approach of the general practitioner to deep phlebitides of the leg]. The author recalls that it is not only difficult but often impossible to diagnose venous thrombosis and to establish the frequency with which pulmonary embolisms are not recognized. He also deals thoroughly with the subject of anticoagulant therapy. He does not consider age to be a contraindication but does regard lesions that bleed as such. However, lack of discipline on the part of the patient and his family constitutes a real contraindication of a psychological type, in certain cases. The author considers that the association of anticoagulants and anti-inflammatory drugs is dangerous.


[Cardiologist's approach to deep phlebitides of the leg]. The frequency with which pulmonary embolism remains unrecognized clinically is well known and explains the value of pulmonary scintigraphy when there is the slightest suspicion of pulmonary embolism or in cases of unexplained dyspnoea of effort after a standard cardiac and pleuro-pulmonary examination. The practical value of a regular pre-operative electrocardiogram and of anticoagulant treatment during the acute phase of myocardial infarction are emphasized. Certain precautions to be observed during the use of antivitamins K in cases of heart failure are outlined.


[Approach of the gynecologist-obstetrician to deep phlebitis of the leg]. The authors recall that early diagnosis and treatment are essential if cure without sequelae is to be obtained. The principle of treatment is based on two essential phases : heparinization (with continuous infusion), antivitamins K, which follow on. Several products, known empirically, may be used in addition, either during the acute phase (hydergine, infiltrations of novocaine, etc.) or during the secondary phase (vitamins P associated with vitamin E, ETC.). Special points :phlebitis during pregnancy requires heparin treatment of short duration. Antivitamins K are strictly contraindicated and ineffective ; great importance is attached to prophyllaxis.


[Psychiatrist's attitude towards deep phlebitides of the leg]. Intervening at the end of the debate, the psychiatrist may be tempted to analyse the role played by the therapist's anxiety in the sometimes impassioned discussions on certain aspects of the preventive treatment of phlebothromboses. How can one remain indifferent to the risk of a pulmonary embolism ; these are sometimes mortal following such common happenings as childbirth, a simple surgical operation, or a sleep cure? In the domain of psychiatric diseases, the problem has been considered solved over the last ten years in that the technique of daily active and passive mobilization has been rigourously applied each time that treatment necessitated rest in bed : in effect, this technique alone has resulted in the complete disappearance of phlebothrombosis and its resulting embolic complications in both hospital services and clinics.


[Our experience with functional ascending cinephlebography]. Over the last three years, ascending, functional cine-phlebography has been used on 43 patients with different lesions of the venous system. The patient is placed in the decubitus dorsal position, on a radiological table inclined at 70 degrees. The opaque liquid is injected into the dorsal vein of the foot. Its movement is helped by the flexing of the muscles of the leg, and is followed on a screen. This method makes it possible to follow the morphological and functional aspects of the veins of the lower limbs. In this way it is possible to assess valvular function, the location of the perforating veins and their competence, the limits of a thrombosis, and the therapeutic results. This examination, which is painless and harmless, makes it possible to improve the precision of the diagnosis in patients with different vein lesions, and gives most valuable information on the functioning of the venous system of the lower limbs.


[Anticoagulants and the prevention of deep venous thrombosis of the leg]. Because of its frequency, the risk of migration to the lungs, and the gravity of the sequelae, phlebitis requires prophylaxis even more than a curative treatment. The ideal prophylactic agent should have, on one hand, an efficacity equal or superior to that of existing therapeutic agents--heparin and antivitamin K--and, on the other hand, should be easy to administer, should not result in haemoragic complications, and should not necessitate complex laboratory tests, these last three conditions not being fulfilled by either heparin or by the antivitamins K. These disadvantages probably explain the present vogue for anti-aggregant substances. Nevertheless, the knowledge of the primordial role of stasis and the phenomena of coagulation, and not least the platelets, in the matter of venous thrombogenesis, and knowledge of the results of studies on experimental thrombosis and of the first clinical trials lead to the conclusion that it is dangerous, at least at the moment, to abandon therapy for the prevention of venous thrombosis the efficacity of which is certain (heparin), in favour of substances the efficacity of which only hypothetical(anti-aggregants).


[Aspirin as treatment for platelet aggregation]. The efficacity of therapy against platelet aggregation, as a preventive treatment in cases of venous thrombosis has been questioned : however, some good, little known pieces of work suggest that such treatment is of value.


[Fibrinolytics and defibrinating agents]. Therapeutic fibrinolysis represents the only logical means of curing thromboses, by assuring the destruction of the thrombus. This kind of therapy, which was introduced clincally over 10 years ago, has been used on only a limited scale because of the high risk of haemorrhage and the need for highly specialized laboratory control tests. Different methods of administration, overcoming one or other of these disadvantages, have resulted recently in its wider use but this has been accompanied by a reduction in efficacity. The very satisfactory clinical results obtained in some cases remain limited and thus in this context the indications should not be restricted.


[Biological supervision of heparin therapy]. Laboratory surveillance of heparin therapy includes a simplied investigation of haemostasis before the treatment (Quick's time, the cephalin-kaolin time, fibrinogen, platelet count) and requires exact adherence to the timetable of injections and taking of samples. According to the degree of hypocoagulability desired, there is a choice between the three tests most often used (Howell's test, heparinaemia, cephalin-kaolin time). For the control of a high degree of hypocoagulability the Howell's time is the best guide. On the other hand, for the surveillance of moderate hypocoagulability (preventive treatment) it is preferable to combine two of these three tests.


[Aspects of defibrinogenation therapy].

[Aspects of defibrinogenation therapy]. Fibrinolysis threatment works by means of enzymatic action. It is an effective therapy for occlusive disease of the arteries at Fontaine's stages III and IV. New developments in this treatment will be of interest to phlebologists in the near future. No studies have been reported in the world literature that broaden the present indications : critical study is still required.


[Anti-K vitamins].

[Anti-K vitamins]. Antivitamins K remain the anticoagulant of choice when treatment lasts several days, because they can be ingested orally, and they require relatively in frequent laboratory tests, and because of the absence of any superior haematological treatments for thrombosis. Physiological studies have explained the effects on the anticoagulant action of the antivitamins K, of imbalance of the intestinal microbial flora and of pathological changes in diuresis. This knowledge is indispensable for national treatment. Surveillance by means of laboratory tests remains indispensable but continues to pose practical problems, as non-specialized biologists have difficulty in achieving the necessary basic conditions (quality of venous puncture, control and test...). Determination of the Quick time remains the most practical method. Laboratory determination of the different constituents of the prothrombin complex makes it possible to regulate perfectly the treatment with antivitamins K of a patient who is also receiving heparin.


[Place of anti-inflammatory agents in the prevention of deep phlebitis]. The inflammatory reaction includes, after an initial tissue lesion, a catabolic phase with proteolysis, an exudative reaction phase, and finally an anabolic phase with the formation of an inflammatory granuloma. The reaction should be considered, however, as an initial inflammation, rapid and limited to the affected tissues, and a secondary inflammation induced at a distance by a humoral mechanism with the appearance of pathological globulins. Only certain anti-inflammatory agents act at these two levels : steroids and non-steroids. Corticosteroids can be used effectively in small doses. Courses of salicylates are difficult to manage and are not standardized. Fenamates and indometacine lead to psychiatric disorders. The only useful drugs are phenylbutazone and hydroxyphenylbutazone. These two drugs can be used alone, or in combination, or eventually being superseded by anti-coagulants. As they are derived from pyrazolidine, they are above all preventive. Their absorption in the digestive tract is rapid and almost complete ; the maximum plasma concentration occurs 2-4 h. after injection. Delayed accidents occur 7-15 days after the last dose. Suppotanderil and suppophenylbutazone are used at the dose of 250ml, 2 or 3 times a day. They may be combined with AVK depending on the clinical signs and the prothrombin and Howell's time. These drugs are contraindicated in patients with ulcers, with haematological diseases, and with severe cirrhosis. They should always be replaced straight away by anti-coagulants in patients with valve prostheses or with severe rhythm disorders.


[Prevention of complications of ligation of the inferior vena cava in recent emboligenic phlebitides]. Ligature of the inferior vena cava, which is often necessary, is usually complicated by severe oedema of the lower limbs. The wearing of an appropriate support bandage over a period of several months will overcome this oedema.


[Heparins].

[Heparins]. For the therapist, there is only one heparin, characterized by its anticoagulant action, but two methods of administration : intravenous and subcutaneous. Heparin is a true anticoagulant, and directly opposes fibrin formation (antithrombotic action) and potentiates the inactivation of prothrombinase ; this global action, immediately effective, makes heparin undoubtedly superior to the antivitamins K. Nevertheless, its action on thrombogenesis is incomplete : it reacts only slightly or not at all on platelet aggregation and fibrinolysis. In the treatment of phebitis, its efficacity is closely bound with its rational use : early use, continuous and sufficiently prolonged infusion, and carefully adapted dosage are the key factors. The practice of interrupted intravenous injections should be abandoned because it is illogical and dangerous. The subcutaneous method ensures a heparinotherapy in all ways closely comparable with the ideal perfusion. Accidents during heparin therapy are neither more frequent nor more serious than those of a really efficient treatment with antivitamins K. At present, heparin is our most effective weapon in the prevention of post-surgical phlebitis.


[Vasomotor substances and anti-inflammatory agents in the treatment of phlebitis]. Intrafemoral injections of substances known as "vasodilators" are still of the utmost value in the treatment of deep phlebitis as are the anti-inflammatory drugs, particularly in their injectable forms (Butazolidine, Ketazone). The indications are : cases of phlebitis that are just developing ; failure of anticoagulants ; and contraindications to the use of anticoagulants, notably phlebitis during pregnancy. As always in the treatment of phlebitis, therapeutic results are only complete and lasting if an effective support bandage is also applied.


[General surgeon's approach to deep phlebitis of the leg]. The therapeutic problems of the general surgeon, faced with a case of deep phlebitis of the lower limbs, differ according to whether it is diagnosed before or after surgery. If possible, pre-surgical phlebitis should be treated before the operation. Heparinotherapy remains the basic treatment. But there are numerous arguments against, or for the modification of, its use : old age, haemorrhagic lesions, haemorrhagic risks during surgery, or simply great operational urgency. In all these cases, an elastic bandage is invaluable. Treatment of post-operative phlebitis is also based on the heparins, combined if necessary with antibiotics and corticoids, but these products can result in iatrogenic complications (ulcers, haemorrhage). It is often difficult to choose between embolic and haemorrhagic risks ; it is always easy to apply an elastic bandage which suffices in most cases to remove the inflammatory signs of the phlebitis. This problem is not so frequent since systematic prevention has made post-operative phlebitis more rare. The use of anticoagulants in vascular surgery seems to the authors to be not so much an effective therapeutic method as a method to be feaved close surveillance of coagulation is indispensable during treatment.


[Preventive and therapeutic approach to deep phlebitis of the leg]. Preventive and therapeutic approaches in cases of deep thrombosis of the lower limbs.