Identification of Neisseria gonorrhoeae by carbohydrate disc reactions on a modified fermentation medium.

The identification of Neisseria gonorrhoeae by the use of a carbohydrate disc reaction on a modified fermentation medium is described. 70 out of the 71 strains tested produced detectable acid in 18--24 hours from the dextrose disc and no acid from Maltose, sucrose or lactose discs. One strain required 48 hours for good growth and acid production from dextrose disc only. The carbohydrate disc method was compared with a standard fermentation method using sugars incorporated in serum-free medium, 64 out of 71 strains of gonococci tested were identified after 18--24 hours incubation. All the strains gave clear-cut confirmatory results after 48 hours incubation. The importance of serum-free fermentation media in the identification of gonococci in tropical areas where meningococcal infections are also prevalent is discussed.


Pseudomonas colonization in cystic fibrosis. A study of 160 patients.

We investigated the role of Pseudomonas aeruginosa colonization in the respiratory tracts of cystic fibrosis (CF) patients to relate the effect of this colonization to progression of bronchial airway pathologic conditions and to the patients' clinical progress, and to identify predisposing factors to persistence of P aeruginosa colonization and bronchial tree damage. Half of 160 CF patients studied had persistent P aeruginosa respiratory tract colonization; the other half had none. Pseudomonas aeruginosa seems to have an exclusive propensity for the respiratory tract and may appear at any age. Treatment with antibiotics, including aminoglycosides, failed to eradicate P aeruginosa. The continuous use of antibiotics seemed to contribute to the persistence of P aeruginosa and the appearance of mucoid strains of P aeruginosa.


Intrathecal gentamicin for refractory gram-positive meningitis.

The mortality for meningitis due to Staphylococcus aureus or Listeria monocytogenes remains high, ranging from 32% to 77%. We treated a patient with staphylococcal meningitis refractory to methicillin sodium and oxacillin sodium, and a patient with Listeria meningitis refractory to penicillin G potassium and ampicillin sodium; both patients were cured when intrathecal gentamicin sulfate was added to the regimen. The combination of intrathecal gentamicin and a penicillin may be beneficial in refractory staphylococcal or Listeria meningitis.


Massive theophylline overdose. Rapid elimination by charcoal hemoperfusion.

Shock, seizures, cardiac arrhythmias, and respiratory and cardiac arrests developed in a patient who ingested 8.5 g of theophylline. Her condition improved and her serum theophylline concentration decreased from 170 to 20 mg/ml during six hours of charcoal hemoperfusion. Theophylline was removed from the serum by the uncoated charcoal column, as shown by an extraction efficiency approaching 100%. The maximum charcoal clearance of theophylline was 163 ml/kg/hr. The average endogenous theophylline clearance in adults is 50 ml/kg/hr and that achieved with hemodialysis is only 24.3 ml/kg/hr. Uncoated charcoal efficiently removes theophylline from the serum; charcoal hemoperfusion should be considered in severe theophylline toxic reactions.


Prevalence of hepatitis B surface antigen and antibody in healthy subjects and patients with liver disease.

The frequency of Hepatitis Bs antigen and antibody was determined in healthy subjects and patients with acute and chronic liver disease. The frequency of HBs Ag in healthy subjects was 2.9% and HBs Ab 35%. The high prevalence of antibody in normal individuals suggests a constant non-parenteral sub-clinical exposure to hepatitis virus. Thirty-three per cent patients with acute viral hepatitis, 20% with cirrhosis and 10% with hepatocellular carcinoma were HBs Ag positive, while HBs Ab was detected in 22% cases of acute viral hepatitis and 37% with other liver disorders. This pattern of prevalence of HBs Ab suggests that hepatitis B virus may be an important etiological agent in acute and chronic liver disease in Pakistan.


Tetanus neonatorum treated by a single high dose of A.T.S. subcutaneously around umbilicus.

Thirteen cases of neonatal tetanus were treated conservatively between 1976 and 1977. A single dose of A.T.S. was infiltrated subcutaneously around the umbilicus and sedation and antibiotics were given as required along with special nursing care. In a previous study (Rathore 1976) large amounts of A.T.S. were given in divided doses by both intravenous and intramuscular routes, the mortality rate was 74 per cent, while in the present series the mortality was reduced to 30.7 per cent.


Antitoxin treatment of tetanus.

A random study of 300 cases suffering from tetanus was conducted at the Lady Reading Hospital Peshawar. Three groups each of hundred patients were formed depending on the dose of A.T.S. administered. No particular difference was noted in the mortality of groups receiving 100,000 units and 20,000 units. A dose of 20,000 units is thus sufficient for most of the tetanus cases. 1000,000 units A.T.S. may be given to postpartum and abortion cases where the infection is more generalised and severe.


Sub-specificities of hepatitis Bs antigen.

A preliminary survey of HBsAg subtypes shows that ayw is the most common subtype in Pakistan. adw. was detected in one blood donor and ayr in a Baluchi female with acute viral hepatitis.


[Oxygen transport by solutions for blood replacement in comparison with other infusion solutions (author's transl)].

To investigate the oxygen transport capacity of solutions for blood replacement the oxygen solubility coefficients (ml/ml atm) at 37 degrees C of 12 solutions for volume replacement were determined and compared with those of 12 solutions for parenteral nutrition, 4 electrolyte solutions and 5 solutions for osmotherapy. All solutions for volume replacement have lower values for oxygen solubility than human plasma which shows a very constant oxygen solubility value even under extreme conditions. For clinical use of volume replacement solutions it is recommended that the oxygen solubility of the substitute be considered when any of the following conditions presents: a) large amounts are infused (hemodilution), b) isobar of hyperbar oxygen therapy is employed (hyperoxia), c) the body temperature is lowered (hypothermia). This is valid especially in the case of any impairment of the microcirculation.


Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse.

NZB X NZW F1 mice initiated on calorie restriction at weaning or at 4 to 5 months of age or initiated on moderate protein restriction at weaning, were afforded significant protection from the development of immune nephritis. Whereas animals on normal calorie intake demonstrated deposition of immune reactants in glomerular basement membrane-oriented pattern, those on either protein or calorie restriction exhibited mesangial confinement of immunoglobulins and complement. Associated with these divergent patterns of immune deposition, mice on normal calorie intake evidence extensive cellular proliferation and glomerular sclerosis while dietary restricted mice demonstrated virtually no hyalinization and only mild cellular proliferation. Autoantibody formation of calorie-restricted animals was significantly decreased compared to mice fed a normal diet. Thus, moderate dietary restriction may serve as either a prophylactic or effective therapeutic approach to ongoing autoimmune disease.


Immunohistochemical localization of histaminase (diamine oxidase) in decidual cells of human placenta.

An immunohistochemical technique has been developed for the localization of histaminase (diamine oxidase) in human placenta. The procedure utilizes antibody to highly purified human placental enzyme prepared in rabbits. Histaminase is shown to be present in the cytoplasm of the decidual cells of the maternal placenta; the staining is specific and can be removed by preabsorption of the antisera with purified antigen. The present demonstration of histaminase in the maternal portion of placenta confirms previous biochemical data suggesting that the enzyme is not a fetal product in this tissue. This study also provides further evidence that the presence of histaminase in some human tumors and in normal tissues like kidney and intestine is the result of the expression of a mature and not a fetal genome.


Acquired auditory verbal agnosia and seizures in childhood.

The syndome of acquired aphasia with associated seizures in children has been known since the first report in 1957. Since then, 42 cases have been reported. This paper presents a review of these cases and discusses clinical features of three additional children in whom the specific syndrome of auditory verbal agnosia was identified. Presenting features, medical and neurological findings, and results of detailed psychometric and speech and language evaluations are discussed. The syndrome should be suspected in any child who develops loss of previously acquired language, preceded, accompanied, or followed by seizures. Joint diagnostic evaluation and therapeutic planning by neurologists, speech-language pathologists, and teachers are recommended.


Cerebral hypothermia and circulatory arrest. Review and commentary.

Through the application of low-temperature technology, the critical limits of circulatory arrest to the mammalian brain--the most complex of all body organ systems--can be significantly extended. This presentation reviews three recently developed methods of cooling the brain. The first demonstrates the unique preservation of cerebral tissue as an isolated organ near 0 degrees C with donor perfusion reanimation. The second emphasizes the ability of the intact animal to literally cool its own brain when a simple extracorporeal shunt is utilized. The third outlines a technique of direct hypothermic infusion of the ventricular pathways to achieve deep temperature reductions in brain tissue. Their clinical applications and implications are discussed.


Modification of visual functions of the parietal lobe at early age in the monkey.

In addition to the visual pathway ending in the visual cortex, visual information is also processed in the associative areas of the cortex. We have studied the posterior parietal association area (Brodmann's area 7), and in our sample about 40% of the neurons were influenced by visual stimulation or ocular movements. The visually activated neurons in this region in normal adult monkeys have large, binocular receptive fields and they respond well to all moving visual stimuli near the animal. They do not differentiate between different patterns of visual stimuli but respond well to objects of interest, such as food, drinks, new objects, etc. Many visual neurons also respond to somatic stimulation. Preliminary experiments on two young monkeys suggest that the visual input into area 7 is strongly modified by early visual deprivation. In one monkey monocular deprivation lead to total absence of any influence from the deprived eye to area 7. No deprivation effect was observed in the lateral geniculate nucleus of the thalamus and the effect in area 7 was stronger than in the visual cortex (area 17). One monkey raised with bilateral eye closure was behaviourally blind after the opening of the eyes and remained so for the observation period of one month. In area 7 of this monkey the proportion of recording sites responsive to visual stimulation was sharply reduced. In kittens binocular deprivation is known to effect the function of the visual cortex much less than monocular deprivation. It seems possible that at early age inputs representing different sensory systems compete for influence in the associative cortical areas in the same way as there is competition between inputs from the two eyes to the visual cortex.


The significance of antidromic potentiation and induced activity in the retina.

It is argued that "The significance of antidromic potentiation and induced activity in the retina" (the title of this article) concerns two identical effects and that both are the outward sign of the existence of a specific organization in the retina. For this reason they can serve as a valuable criterion for identifying activity in this organization. This activity is assumed to be in the nature of a self-excitation by positive feedback in the amacrine circuits of certain Y-cells. Relevant literature has been reviewed. These Y-cells, whose spectral response curve is of the dominator type, play a prominent role in stimulation by intermittent light and in the perception of luminosity. Several properties of intermittent stimulation are mentioned and held to motivate a renewal of the attention of visual experimenters to 'flicker' and its after-effects.


[The immediate reconstruction of a large lip-chin defect with two muscular pedicled and innervated island flaps (author's transl)].

Different methods of defect closure in the lipchin region through lateral advancement-flaps have been described by Bernard, Fries, Hertig, Meyer and others. Is there not enough material available, can neck-, breast-or forehead flaps cover the defect, although they do not fulfill the demands for a satisfactory restoration of specific function. In the following work is the possibility of covering of a three layered facial defect with a combined skin muscle flap taken into consideration in view of the disadvantages of a simple or doubled skin flap. By this operation method the procedure consists of preparing various sized cervical island flaps which are connected with on the mastoid pedicled M. sternocleidomastoideus. We are describing a case of extensive tumorresection in the lip-chin area with neurofibromatosis Recklinghausen, whereby we have closed a large defect with two separately laid on muscle-pedicled, innervated island flaps from the fossa supraclavicularis. These bilateral compound flaps fulfill the demands of an immediate restoration of contour and prominence in this area. Apart from this they allow satisfactory voluntary activity, unpleasant dribbling of saliva is prevented.


Comparative in-vitro activity of ticarcillin and carbenicillin against 100 clinical isolates of Pseudomonas aeruginosa.

The in-vitro activity of ticarcillin was found to be greater than that of carbenicillin against 97 out of 100 strains of Pseudomonas aeruginosa which were recently isolated from clinical specimens at the Royal Perth Hospital complex. These results indicate that ticarcillin should be considered for use in place of carbenicillin for treating infections caused by P. aeruginosa.


[Radioimmuno-assay of TSH before and after TRH in 350 patients with previous resection of euthyroid goiter (author's transl)].

Radioimmuno-Assay (RIA) of Thyroid-Stimulating-Hormone (TSH) was performed before and after i.v.-injection of Thyrotropin-Releasing-Hormone (TRH) in 350 patients subsequent to previous resection of euthyroid goiter to find out the optimal treatment schedule for preventing recurrent goiter. In patients without recurrent goiter the dosis of thyroid hormone was considered to be sufficient, if the difference in TSH-levels before and after TRH (delta-TSH) was equivalent to or less than 10 microunits/ml. In patients with recurrent goiter the optimal suppressive dosis of thyroid hormone was accepted for a delta-TSH less than or equal to 2,5 microunits/ml. 126 out of 135 patients, who were set on an immediate and continuous postoperative treatment were free of goiter, 58 presented a delta-TSH less than or equal to 10 microunits/ml (average interval of treatment = 2,5 years), 68 patients had elevated delta-TSH (average interval of treatment 2,1 years) as a sign of insufficient treatment. In 9 patients recurrent goiter was detected in spite of "adequate" treatment. 41 out of 57 patients, set on delayed and partly continuous, partly discontinuous treatment had recurrent goiter (in average after 10 years). delta-TSH was not indicative. 158 patients without any treatment had borderline or slightly increased delta-TSH (in average after 10 years). 122 of these 158 patients had recurrent goiter, 36 were free of goiter. The results favor the necessity of treatment with thyroid hormones starting immediately after operation and with continuous treatment. The combined use of TSH-RIA and TRH-test reliably informs about the individual thyroid hormone dosis necessary for prevention or treatment of recurrent goiters.


[Exolipases of some Pseudomonas species].

The production of exolipase was studied in various Pseudomonas species, most of which did not possess the lipolytic activity in the conditions of the experiment, whereas in some strains this activity was rather high. The highest activity was displayed by the Pseudomonas fluorescens 533 strain and its mutant obtained upon UV irradiation. Lipase biosynthesis depended on the composition of a growth medium, the highest lipolytic activity being found on media with a high content of complex organic substances. No correlation was established between the growth and the lipolytic activity. A lipase preparation was isolated from the Ps. fluorescens 533-5b mutant, partly purified by precipitation with ammonium sulphate and dialysis, and its response to the action of inhibitors and heavy metal ions was studied. The enzyme activity was inhibited by these ions, and stimulated by Mg2+ ions. EDTA was found to be the strongest among all the inhibitors tested.


Fluorometric determinations of the relative immunoglobulin content of plasma cells of patients with monoclonal gammopathy.

The relative cytoplasmic immunoglobulin content of fixed plasma cells taken from the bone marrow of five patients with myeloma and five patients with benign monoclonal gammopathy was determined with a microscope fluorometer. In eight of the ten piasma cell populations studied, the distribution of the fluorescence intensities was close to normal. In three of these eight populations a significant difference in the variances of the heavy and light chain fluorescence intensities was found. Variances of heavy and light chain fluorescence intensities were smaller in patients with an immunoglobulin A-type gammopathy than in those with an immunoglobulin G-type gammopathy. No difference was found if normalized relative frequency distribution patterns of heavy or light chain fluorescence intensities of patients with myeloma were compared with those of patients with benign monoclonal gammopathies.


Continuous cultivation in a chemostat of the phototrophic procaryote, Anacystis nidulans, under nitrogen-limiting conditions.

Anacystis nidulans was grown photoautotrophically in a chemostat in the presence of light, air and CO2 as the sole carbon source. Either the amount of the nitrogen source in the medium or light intensity were used as growth-limiting parameters. 1. Cells of high glycogen content obtained by pre-incubation under nitrogen starvation conditions maintained their glycogen content during continuous cultivation. Both growth rate and the amount of cell-mass and of glycogen depended on the nitrate content of the medium and the light intensity. The values for the growth rate, the maximal rates of glycogen synthesis and of cell mass formation were 0.1 h-1, 6 mg/l.h and 17 mg/l.h, respectively. 2. Cells without glycogen which had been transferred from an exponentially growing batch culture to chemostat conditions showed increasing rates of growth and of cell mass formation when the light intensity was increased. A determination of specific values resulted in 0.15 h-1 for growth rate and 23 mg/1.h for cell mass formation. 3. The chemostat apparatus is described in detail.


[Anesthesiological problems in maxillo-facial surgical interventions and reconstructive plastic surgery].

11 years of anaesthesiological experience in maxillofacial and reconstructive plastic surgery (1-4-1966/1-4-1977) are reviewed. The problems connected with these operations are examined. On the basis of localizations, types of operation and surgical requirements, the problems of greatest importance in these branches of surgery may be indicated in the following 5 parameters: 1. Control of the respiratory ways with naso-tracheal intubation under direct view or blind (more than a thousand cases), oro-tracheal intubation: their indications and contraindications as alternatives to pre- intra- and postoperative tracheotomy. 2. Local control of bleeding. 3. Arousal and prevention of possible postnarcotic complications. 4. Prevention and treatment of postoperative oedema. 5. Nutrition of the patient undergoing surgery. In the interests of history, the superseded problem of whether to use local anaesthesia and general anaesthesia in maxillofacial surgery is mentioned and the various problems are discussed exhaustively. Personal anaesthesiological conduct is then specified in relation to the parameters examined and results reported. The importance in certain endo- and extraoral operations of prolonged intubation in the immediate postoperative period (10-15-30 hours) with respect to the indication for postoperative tracheostomy is highlighted. Apart from certain special pathological situations, tracheostomy is rather exceptional and is no longer employed on a routine basis as it was 2-3 years ago.


[EEG-results in early-treated children with phenylketonuria 4 through 10 years under treatment (author's transl)].

EEG-results in 21 children with Phenylketonuria (PKU), put on a diet at least since their 3rd month of life, now aged 4 through 10 years, with normal psychomotor development, lacking abnormal neurological signs, are compared with the results in 796 healthy children of the same age. Visual evaluation and frequency analysis of the background activity of the EEGs reveal no differences between children with PKU and controls. Generally, there is no close correlation between mean plasma levels of phenylalanine (phe-means) during treatment, and the composition of the EEG when combined age groups are compared. But a trend can be demonstrated: In the small group of 8 years old children phe-means up to 6 mg-% can be associated with a faster (alpha), and phe-means above 6 mg-% with a slower (theta) background activity. The frequency of metabolic derailment (single phe-values above 10 mg-%) does not correlate with the EEG. Focal and generalized hypersynchronous activity (HSA) is observed significantly more often even in early treated, normally developing children with PKU. In children aged 4--8 years, HSA is associated with a high proportion of slow waves compared with those who do not display HSA. In children 9 and 10 years old, however, no such differences can be seen. It is hypothesised that even early treated children with PKU, in their first years show a retardation in the development of their background activity but catch up by 9--10 years. It still remains uncertain whether further age-appropiate development of the EEG can be observed after liberating or discontinuing the dietary regimen at this age.


[Success at school of children with early recognized phenylketonuria. Catamnesis of 50 children whose dietary treatment was started within their first or second month of life (author's transl)].

The success at school of 50 children is evaluated whose phenylkenuria was detected within the first 8 weeks of life and treated since. Recent reports on normal psychological development can now be augmented by this criteria established outside the hospital. For the evaluation the following items were taken into account: age at start of schooling; postponed admission to school; repetition of a class; move to secondary schools, and social background. The success at school is further confirmation of a normal mental development in these children, and a normal school leaving certificate or later an ordinary occupation are to expected.


[Participation of rat immunoglobulin light chains of the kappa and lambda type in formation of antibodies to the polysaccharide of group A streptococcus].

The role of light kappa and lambda chains and also allelic variants of kappa chains of rat immunoglobins in the formation of antibodies to beta-N-acetyl-glucosamine polysaccharides of streptococcus group A of inbred rat strains MSU, WAG, August and hybrids of the first generation (MUS X WAG)F1 and (MSU X August)F1 was studied. From individual sera of immune rats fractions of specific antibodies to beta-N-acetyl-glucosamine were isolated. These antibodies differ in their affinity to antigenes. The retio of molecules with kappa and lambda light chain types was determined for the fraction of specific antibodies. The ratio of molecules kappa and lambda depends on the affinity of antibodies to beta-N-acetyl-glucosamine and on the genotype of the animals studied. Data obtained allow to conclude that differences in the functional activity of lambda chains between strains WAG and August, on one hand, and strain MSU, on the other, do exist. Functional differences releaved between these rat strains were confirmed by analyzing corresponding antibody fractions to beta-N-acetylglucosamine in F1 hybrids. Differences between allelic variants of kappa chains in the formation of antibodies to beta-N-acetylglucosamine of polysaccharides were not found.


[Synthesis of virus-specific products following introduction of tobacco mosaic virus RNA pereparations and the native virus into acetabularia].

The possibility to synthesize the viral-specific products after microinjection of Tobacco mosaic virus (TMV) preparations and the TMV RNA into the single-celled seaweed Acetabularia was studied. The accumulation of the newly synthesized protein and double-stranded RNA 24 hours after injection of TMV RNA and native virus preparations was demonstrated by immunological and immunofluorescent methods. The virus titer sharply dropped 3--4 hours after introduction into Acetabularia and in 48 hours it reached a maximum level. The presented data showed the possibility of TMW RNA replication and translation involving formation of viral-specific proteins and the production of a virus of full value in the Acetabularia cell.


[Conformational isomers of rat liver 5S ribosomal RNA].

The rat liver 5S RNA when denaturated by urea or EDTA, or even without any special treatment, undergoes conformational changes leading to the formation of three electrophoretically distinct isomeres of the molecules with relative mobilities 0.39, 0.44 and 0.47. The band with the slowest mobility corresponds apparently to the native 5S RNA since it is specific for both freshy isolated and renaturated 5S RNA. Moreover, it was found that denaturation of the immobilized 5 S RNA decreases significantly its ability to form a complex with the rat liver 60S ribosomal subunit proteins L6, L7, L8, L18 and L35.


Mutagenic effects of petrol in Drosophila melanogaster I. Effects of benzene and 1,2-dichloroethane.

Commercial petrol and two of its components, benzene and 1,2-dichloroethane, were tested for mutagenicity in Drosophila melanogaster. The chemicals were given to larvae through their food supply. A genetically unstable sexlinked test system caused by a transposable genetic element was used. Mutagenicity was measured by the frequency of somatic mutations for eye pigmentation. Commercial petrol and 1,2-dichloroethane showed mutagenic activity. With the system used, benzene did not show any mutagenic activity. The high frequency of mutations induced by 1,2-dichloroethane indicate the existence in Drosophila of a metabolic activating system.


The influence of electrostatic and magnetic fields on mutation in Drosophila melanogaster spermatozoa.

Canton-S Drosophila melanogaster males were exposed to electrostatic and magnetic fields for 24 h to determine the influence of low energy fields on the production of sex-linked recessive lethal mutations in the mature, motile sperm. To detect sex-linked recessive lethal production in mature sperm the standard Muller-5 test was done. Exposure of the males to the magnetic field or the electrostatic field did not significantly affect the mutation frequency in mature sperm.


Prevention of the Wernicke-Korsakoff syndrome: a cost-benefit analysis.

The Wernicke-Korsakoff syndrome is a thiamine-deficiency disorder occurring primarily among alcoholics. To determine the economic feasibility of preventing this disease by fortification of alcoholic beverages with thiamine, we compared the cost of fortification with the cost of institutionalizing alcoholics with the disorder. The estimated annual incidence of institutionalization is eight per million adult population. The cost of long-term institutionalization, discounted to present value, is $70 million per year. The cost of adequately fortifying alcoholic beverages is estimated to range from $3 million per year if allithiamines are used, to as much as $17 million per year if thiamine hydrochloride proves necessary. Thus, the cost-benefit ratio may range from 1:23 to 1:4. It is economically advantageous to prevent the Wernicke-Korsakoff syndrome by fortification of alcoholic beverages with thiamine. The stability, safety and marketability of thiamine and the allithiamines in alcoholic beverages should be studied further.


[Duodenal diverticulosis].

The problem of duodenal diverticuli is discussed. The best therapy is reviewed and a personal series compared with those of other workers. In most cases, the medical approach appears preferable, surgery being reserved exclusively for variously complicated cases.


Obstetric factors in cerebral palsy.

A study was carried out on the patient population of two cerebral palsy facilities serving Northeast New York State to evaluate obstetric factors which might be associated with the development of cerebral palsy. A combination of available medical records and a maternal questionnaire was used for analysis. Of 605 contracted, 158 mothers (26%) provided valid and detailed data, and the study was confined to these 158 patients. A positive association was found with increased reproductive loss, prematurity, and vaginal breech delivery. The need to develop and adopt a comprehensive uniform record system for the pregnant patient and her child is underscored. The limitations of a single factor retrospective study are acknowledged.


Hurler/Scheie phenotype. Report of an inbred sibship with tapeto-retinal degeneration and electron-microscopie examination of the conjuctiva.

An inbred sibship with corneal opacities and deficient alpha-L-iduronidase activity showed signs of a Hurler/Scheie phenotype. The children were of normal intelligence. In one of the children, electron microscopy of the conjunctiva showed membrane-bound intracellular vacuoles and the electroretinogram was extinguished. The consanguinity of the parents is taken to indicate the presence of homozygosity of a mutant gene different from both the Hurler and Scheie mutants, thus rejecting the concept of a genetic compound in our patients.


The treatment of bacterial endophthalmitis.

Restoration of good visual acuity following bacterial endophthalmitis is dependent on prompt diagnosis, immediate treatment, proper selection of antibiotics, high-dose parenteral and periocular antibiotic therapy, and systemic and periocular corticosteroids. Antibiotic selection should be based on the statistical incidence of pathogens rather than on the result of a Gram stain from the aqueous or vitreous humor. Recent experimental studies in the primate eye suggest that there is little to choose between the subconjunctival and retrobulbar routes of antibiotic administration. The role of intravitreal injection of antibiotic, although promising, requires further definition.


Iron therapy and refeeding in experimentally malnourished rats.

1. Rats suffering from protein-energy malnutrition were found to have low serum iron, low PCV, and low hemoglobin concentrations. 2. Oral iron supplement during the refeeding of these animals caused various types of infection, the severity of which was related to the dose given. 3. A close association between high serum iron, low serum transferrin, and high incidence of bacterial infection was found. 4. A high protein diet without any oral iron supplement was found to raise the PCV and hemoglobin concentration to the same levels as a high protein diet containing 65 mg iron/kg body wt/day, although this dose of iron was sufficient to produce infection in the malnourished rats during refeeding. Speculation Iron supplementation during the treatment of children with protein-energy malnutrition may predispose to bacterial infection, the severity of which depends on the dose of iron given.


Prolonged apnea in infant monkeys resulting from stimulation of superior laryngeal nerve.

We measured characteristics of apnea resulting from electrical stimulation of the superior laryngeal nerve (SLN) in 28 anesthetized infant monkeys ranging from a gestational age of 141 days to 49 days postterm and in four adult monkeys. Progressive reduction in ventilation accompanied weak suprathreshold SLN stimulation. Poststimulus apnea followed stronger stimulation. Apnea duration was directly proportional to stimulus duration, provided that stimulus intensity was at least 1.5 X threshold. Poststimulus apnea periods were briefer in older infants and did not occur in adults. Pao2 measurements in four animals showed that lower values were associated with the longer poststimulus apnea episodes. Upper airway resistance measurements obtained from a subglottal cannula revealed that glottal closure was transiently associated with the onset of SLN stimulation, but the degree of closure diminished during the course of stimulation and was not present during the subsequent period of apnea. The parameters of SLN stimulation determine specific changes in cardiovascular functions independently of their respiratory effects. The results suggest that a brief afferent input from the SLN may have prolonged effects on respiratory regulation in infants. These persisting effects may be an important consideration in sudden infant death syndrome mechanisms.


Hyperthyroidism in juvenile diabetes mellitus.

Three cases of hyperthyroidism occurring in juvenile patients with diabetes mellitus are presented. The presence of hyperthyroidism should be suspected in patients with diabetes mellitus when goiters develop and when there is unexplained weight loss, tachycardia, tremors, unexplained increases in insulin requirement, or instability of the diabetes with a tendency toward development of ketosis and/or ketoacidosis.


Growth, health, and development after neonatal gut surgery: a long-term follow-up.

Growth and development data on 19 children who survived gut surgery in the immediate newborn period are presented. The follow-up period ranges from seven months to seven years six months, with a mean of three years eight months. Neonates who undergo gut resection are at a higher risk for delay in height and weight gain compared to those who have gut surgery without resection. Six of the 12 children who had gut resection showed delay in height gain and seven showed delay in weight gain. Of the seven children who had gut surgery but no resection, only one showed delay in height and weight gain after the age of 1 year. An individual approach and careful serial follow-ups are recommended for all children undergoing gut resection in the newborn period. Of the eight children who had psychometric testing in the gut-resected group, only two are normal. Three of the four older children in this group show signs of perceptuomotor defects, suggesting the need for subtesting such children at about 6 years of age so that remedial help, if necessary, may be provided when formal schooling begins.


Suppression of visual observing by rhesus monkeys produced by conditioned aversive visual stimuli.

Nine rhesus monkeys were tested in a visual observing situation to determine the influence of conditioned aversive visual stimulation. A set of meaningless visual stimuli was selected on the basis of cumulative frequency and cumulative duration of observing during a pretest phase of the experiment. Three subsets of stimuli (low, medium, high) were formed indicating level of observing during pretesting. A portion of the "medium" category of slides then served as conditioned stimuli in a classical conditioning procedure by being paired with electric shock. Following conditioning the entire set of stimuli was again presented in a visual observing situation. The results showed a significant decrease in both frequency and duration of observing of the slides with conditioned aversive qualities, relative to non-shock control slides. These findings support an aversion-produced suppression of observing relatively unconfounded by methodological, procedural, and other differences existing among previous reports on the role of fear or anxiety in this context.


[Blood prolactin in insulin-dependent diabetics. Basal study and effect of stimulation].

Blood prolactin levels were measured under basal conditions and following the intravenous injection of TRH at time 0, 30, 60 and 120 minutes in 22 men and 21 women insulin-dependent diabetics, aged less than 50 years and not taking any drug influencing prolactin secretion. Prolactin levels were significantly higher (alpha = 0.05) at the 120th minute in male diabetics and under basal conditions and at the 60th minute in female controls. There was no correlation with retinopathy, age and control of diabetes. At the 30th minute, prolactin levels were higher when diabetes was of more recent onset. These results confirm the absence of any participation of prolactin in the development of retinopathy, although variations in prolactin may be seen in association with the presence of diabetes.


[The treatment of congestive heart failure by using vasodilators. I. Physiological basis. Different vasodilators (author's transl)].

The use of vasodilators represents a new approach in the treatment of heart failure. These drugs have the property of causing vasodilatation of either arterial or venous predominance or balanced between these two vascular beds. Arterio-dilators (phentolamine, hydralazine) increase stroke volume and cardiac output by decreasing ventricular afterload. Veno-dilators (nitroglycerine) have little effect on cardiac output but decrease ventricular filling pressure, thereby relieving pulmonary venous hypertension. Mixed vasodilators (Sodium nitroprussideate, trimetaphan) combine these two groups of properties in various degrees. The majority of these drugs can only be administered intravenously, with careful haemodynamic surveillance.


[The treatment of Crohn's disease in the child. 12 cases (author's transl)].

Therapeutic aspects of Crohn's disease in pediatrics are discussed. New renutrition techniques are pointed out: total parenteral nutrition in 4 cases, and constant rate enteral nutrition in 6 cases (with elemental diet). In association with anti-anflammatory and anti-bacterial drugs results seemed very remarkable: in all cases, dramatic clinical recovery, and even radiologic improvement. In two cases surgery appeared to be defered after more than one year of evolution.


The localization of tRNA4Glu genes from Drosophila melanogaster by "in situ" hybridization.

Transfer RNAGlu4 was isolated from Drosophila melanogaster by affinity chromatography. The tRNA was iodinated "in vitro" with Na[25I] and hybridized "in situ" to salivary gland chromosomes from Drosophila. Subsequent autoradiography allowed the localization of the genes for tRNAGlu4 to the right arm of the second chromosome and to the left arm of the third chromosome in the regions 52 F, 56 EF and 62 A.


Pre-proparathyroid hormone; amino acid sequence, chemical synthesis, and some biological studies of the precursor region.

The precursor of bovine proparathyroid hormone was synthesized by translation of parathyroid mRNA in a wheat-germ cell-free system. The amino acid sequence of the NH2-terminal extension (the pre sequence) was determined by repetitive Edman degradation of the polypeptide labeled with radioactive amino acids (radiosequencing). The pre sequence of pre-proparathyroid hormone is (formula: see text) which is followed by the sequence of proparathyroid hormone. It is significant that 20 of the 25 amino acids in the sequence are hydrophobic. This high hydrophobicity is consistent with the proposed role of the pre sequence as a membrane-penetrating peptide. The precursor-specific sequence of 31 amino acids was snythesized chemically by the solid-phase technique. This synthetic peptide was shown to bind to the microsomal fraction of homogenates prepared from extracts of parathyroid glands, a finding consistent with the proposed role of the precursor peptide in the attachment of the nascent chain--mRNA--ribosome complex to the endoplasmic reticulum.


[Diagnosis of malignant neoplasms by studying the changes in the concentration of fetal hemoglobin, hemoglobin A2 and carbonic anhydrases B and C. An application of discriminating function].

This publication proposes the utilization of an analytical discriminatory method in the diagnosis of malignant neoplasia. The multiple variable technique of analysis is suggested employing the quantification of the HbF, HbA2, AcB and AcC. This has already been demonstrated in a previous study which suffered from quantifiable variations important in neoplastic disease. The confidence of the procedure has been proven when applied to 198 known cases, having classified them adequately 94 per cent of the time.


Synthesis of cold-insoluble globulin by cultured calf endothelial cells.

Radiolabeled amino acids were incorporated into nondialyzable protein by cultures of endothelial cells derived from calf aorta. Antibody prepared against purified bovine plasma cold-insoluble globulin (CIG) formed a strong precipitin line upon immunodiffusion against 3H-labeled proteins from endothelial cell culture media. This precipitin line formed a line of identity with the precipitin line formed by anti-CIG and purified CIG. Double-antibody immunoprecipitation of 3H-labeled protein showed that 36.3% of the radioactivity was specifically precipitated by the anti-CIG antibody. Gel filtration and polyacrylamide gel electrophoresis of the immunoprecipitate indicated that it contained a single protein species whose molecular weight was consistent with that of CIG isolated from plasma. When cultured cells were examined by indirect immunofluorescence microscopy, the endothelial cells stained specifically with anti-CIG antibody. These data indicate that cultured endothelial cells derived from calf aorta synthesize and secrete a protein antigenically similar to CIG.


Isolation and characterization of a highly repetitious inverted terminal repeat sequence from Oxytricha macronuclear DNA.

The low-complexity "gene-sized" linear DNA duplexes of the Oxytricha macronucleus sport short inverted terminal repeats; thus, each single strand is capable of forming a circle held together by a duplex "neck" [Wesley, R. D. (1975) Porc. Natl. Acad. Sci. USA 72, 678--682]. We have isolated necks from total, circularized, single-stranded macronuclear DNA by treatment with nuclease S1. Necks represent at least 2.2% of the total DNA, are homogeneous in size (23 base pairs), melt at 55 degrees in 0.18 M Na+, and reassociate extremely rapidly at 22 degrees (Cot1/2 = 1.1 X 10(-5) mol-liter-1.sec) to form hybrid necks of the same thermal stability. From these and other results, we conclude that all necks on all the many thousands of different single-stranded circles are the same. The neck sequence is therefore highly repetitious--found in multiple copies (as inverted terminal repeats at flush duplex ends and probably also internally) on each natural "gene-sized" macronuclear DNA molecule--implying the possible participation of this sequence both in the general vegetative metabolism of macronuclear DNA and in the pre-vegetative process whereby macronuclear DNA is excised from the total Oxytricha genome.


Pseudomonas cytochrome c551 at 2.0 A resolution: enlargement of the cytochrome c family.

The structure of respiratory cytochrome c551 of Pseudomonas aeruginosa, with 82 amino acids, has been solved by x-ray analysis and refined to a crystallographic R factor of 16.2%. It has the same basic folding pattern and hydrophobic heme environment as cytochromes c, c2, and c550, except for a large deletion at the bottom of the heme crevice. This same "cytochrome fold" appears to be present in photosynthetic cytochromes c of green and purple sulfur bacteria, and algal cytochromes f, suggesting a common evolutionary origin for electron transport chains in photosynthesis and respiration.


Immunological screening method to detect specific translation products.

We describe a very sensitive method to detect as antigens the presence of specific proteins within phage plaques or bacterial colonies. We coat plastic sheets with antibody molecules, expose the sheet to lysed bacteria so that a released antigen can bind, and then label the immobilized antigen with radioiodinated antibodies. Thus, the antigen is sandwiched between the antibodies attached to the plastic sheet and those carrying the radioactive label. Autoradiography then shows the positions of antigen-containing colonies or phage plaques. A few molecules of antigen released from each bacterial cell generatean adequate signal.


Chromosomal locations of mouse immunoglobulin genes.

The chromosomal locations of the structural genes coding for the constant portions of mouse heavy (H) and light chain immunoglobulins were studied by molecular hybridization techniques. Complementary DNA probes containing the constant-region sequences of kappa and lambdaI light chain and alpha, gamma2b, and mu heavy chain mRNAs were annealed to a large excess of DNA from a series of eight mouse-human hybrid cell lines that are deficient for various mouse chromosomes. The lines were scored as positive when a high proportion of a probe annealed and negative when an insignificant proportion annealed. Some lines were clearly negative for H and lambda and clearly positive for kappa. Others were positive or intermediate for lambda, positive for kappa and negative for H. Still others, including a line that was selected for the absence of the mouse X chromosome, were positive for all immunoglobulin species. These results demonstrate that the Clambda, Ckappa, and CH genes are located on different autosomes in the mouse. In contrast, the three heavy-chain families exhibited consistently uniform hybridization results, suggesting that the genes for Calpha, Cgamma, and Cmu are located on the same chromosome. A comparison of karyotypic data with hybridization data has limited the possible locations of the Ig genes to only a few chromosomes.


Direct demonstration of immunoglobulin kappa chain RNA in thymus T cells by in situ hybridization.

Mouse thymuses with more than 99% T cells have been reported to contain immunoglobulin kappa mRNA-like molecules (kappa RNA) in relatively large quantities. The present study was undertaken to rule out the possibility that the kappa RNA was mainly a product of a few contaminating B cells of the thymus and to determine whether all T-cell subpopulations contained kappa RNA. By in situ hybridization with DNA complementary to kappa mRNA (kappa cDNA) the following observations were made: 98.5% of thymus cell preparations hybridized with kappa cDNA; the 1.5% unlabeled cells were generally larger and paler staining than the majority of thymus cells. Only 0.015% of thymus cells were intensely labeled and appeared to be plasma cells. Also, 87% of spleen cells hybridized with kappa cDNA; most of these showed similar labeling intensity to the majority of thymus cells. The number of unlabeled cells corresponded to the percentage of hemopoietic cells and macrophages in the spleen. Spleen cells in the range of 0.37-0.85% were intensely labeled and appeared to be plasma cells. The following controls supported the conclusion that the results with thymus and spleen were due to specific hybridization: most of the kappa mRNA-deficient tissue culture cells of the plasmocytoid tumor ABPL-4 did not hybridize with kappa cDNA. The kappa mRNA-producing cells from myeloma PC 3741 hybridized in situ with kappa cDNA. Furthermore, all cells from this tumor and all spleen cells hybridized uniformly with a cDNA probe complementary to most of the total cellular poly(A)-containing RNA species of these cells. These results indicate that T cells of all types in the thymus as well as in the periphery contain substantial quantities of kappa RNA.


Stimulation of fetal hemoglobin synthesis in baboons by hemolysis and hypoxia.

Fetal hemoglobin (Hb F) levels in the peripheral blood of baboons (Papio cynocephalus) increased from an average value of 0.78% to 18.1% during the recovery phase from phenylhydrazine-induced hemolytic anemia. A similar increase was observed in animals exposed to hypobaric hypoxia. Large individual variations in the maximal Hb F levels were observed which could not be correlated with the ages of the animals. Reinduction of hemolysis in two fully recovered animals resulted in Hb F levels that were of similar magnitude as in the preceding episode, suggesting the possibility of genetically determined individual variations in the rate of Hb F synthesis under the same conditions of erythropoietic stimulation. Reticulocytes from the animals subjected to hemolysis of hypobaric hypoxia synthesized similar absolute quantities of Hb F in vitro. The results of the present studies indicate that the physiological switch from the synthesis of Hb F to that of Hb A during ontogeny can be reversed in adult nonhuman primates by conditions of erythropoietic stress known to be associated with high erythropoietin levels. These findings open the possibility that Hb F synthesis in adult humans may be therapeutically modulated in individuals who might benefit from increased levels of Hb F, such as patients with sickle cell anemia.


Large T1 oligonucleotides of Moloney leukemia virus missing in an env gene recombinant, HIX, are present on an intracellular 21S Moloney viral RNA species.

HIX, a recombinant derived from Moloney leukemia virus, has an envelope glycoprotein different from that of the Moloney virus. HIX and Moloney viruses share the majority of the large T1 oligonucleotides derived from their genomes but each possesses a set of distinctive oligonucleotides that lie clustered in corresponding regions in the 3' halves of their oligonucleotide maps. These regions presumably contain envelope glycoprotein coding sequences. The type C viral envelope glycoprotein is believed to be translated from a 21S RNA. Thus, at least part of the region of the Moloney virus genome that is altered relative to HIX was expected to be present on such a species. To test this prediction, we purified an intracellular 21S Moloney viral RNA species and analyzed its large T1 oligonucleotides by two-dimensional polyacrylamide gel electrophoresis. This RNA contains one T1 oligonucleotide that is probably derived from the 5' end of the Moloney virus genome, the Moloney virus T1 oligonucleotides that are missing in HIX, and those that lie to their 3' side on the Moloney virus T1 oligonucleotide map.


Clusters of intramembranous particles on cultured myotubes at sites that are highly sensitive to acetylcholine.

Electrophysiological and autoradiographic studies have shown that the distribution of acetylcholine (AcCho) receptors on uninnervated cultured chicken muscle cells is not uniform. Regions of high receptor density (hot spots 10--40 times more sensitive than surrounding areas are localized as discrete patches or clusters about 10 micrometer in diameter o myotube muscle membranes. Hot spots were also found on fusion-arrested mononucleated myoblasts. We have developed a method for freeze-fracturing monolayer cultures that allows the unambiguous reidentification of membrane patches previously assayed for ACCho sensitivity. The freeze-fractured membranes at physiologically defined hot spots contain aggregates of many (10--20) small clusters of large (10--19 nm in diameter) intramembranous particles. Clusters are found on both fracture faces, but the particle density is much greater on the protoplasmic (P) face than on the extracellular (E) face (about 2000/micrometer2 vs. 700/micrometer2). Some of the particles appear to be composed of five or six "subunits" arranged cylindrically around a central dark dot. Because the aggregates are present at sites of high AcCho sensitivity, it is likely that the intramembranous particles are in some way related to the AcCho receptor molecule.


Toward a mechanism of myoblast fusion.

Myoblasts derived from chick pectoral muscle explants and grown in vitro in low calcium medium are harvested with EDTA. These cells, when agitated in suspension, show a calcium mediated, reversible aggregation which is relevant to myoblast function. With time, progressively harsher methods are required to disrupt the aggregates until, finally, dispersion resistant aggregates and multinucleate cells appear. From these kinetic data we conclude that myoblast fusion results from a sequence of stages including recognition, adhesion, membrane union, and further morphologic changes. Various agents and manipulations, known to inhibit myotube formation, affect these stages differently. Our observations are compatible with protein mediated recognition and adhesion-stages, and with a role for the cytoskeleton, Ca2+, and fluid membrane lipids at a stage at, or just prior to, membrane union. One model consistent with our observations is an adhesive step, possibly via a gap junction-like structure, followed by directed movement of protein, which results in closely apposed or exposed regions of lipid bilayer, which then fuse.


Effects of perphenazine enanthate injections on prolactin levels in plasma from schizophrenic women and men.

Levels of prolactin (PRL) in plasma were determined in schizophrenic women and men after i.m. injections of 50-150 mg perphenazine enanthate (PE). In both sexes PRL levels increased dose-dependently. In men the effect was significant for 2 and in women for 9 days. Biperiden treatment did not influence the effect of PE on the PRL levels. The data support the view that clinically used doses of PE induce a small but significant blockade of central dopamine receptors.


Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone.

The effects of methaqualone on isonicotinic acid hydrazide, 6-mercapto propionic acid, picrotoxin, and strychnine-induced convulsion were studied in mice and the results compared with diazepam. Methaqualone, like diazepam, was found to be a selective antagonist of isoniazid-induced convulsion and a much less effective inhibitor of strychnine convulsion. Methaqualone elicits muscle-relaxant, sedative, and anticonvulsant effects at different dose levels. At low, nonsedative doses the drug produces anticonvulsant effects, and at higher doses, muscle-relaxant and sedative effects. It appears that the mechanism(s) of action of methaqualone in on GABA deficiency or receptor blockade, rather than on glycine receptors.


Antidepressant activity and pharmacological interactions of ciclazindol.

Ciclazindol, a new tetracyclic compound, appears to be a potentially important antidepressant of the same order as amitriptyline, but with significantly fewer subjective side effects. Although as a group the patients treated with ciclazindol lost weight, clinical improvement was observed to be significantly correlated with the weight gain in both groups. The peripheral adrenergic interactions were studied. In the dosage used (100 mg/day) ciclazindol was observed to be a peripheral Na-reuptake blocker with no significant effect on the postsynaptic alpha-receptors. Plasma concentrations of the drug were estimated and their relationship to the therapeutic outcome, side effects, and adrenergic interaction were studied. No significant change in resting BP or ECG was observed following 4--6 weeks' treatment with ciclazindol.


The effects of methylphenidate on repeated acquisition of serial discrimination reversals.

Rats were trained to bar-press for sucrose solution in the presence of one of two stimulus conditions. On each daily training session, the stimulus during which bar-pressing was reinforced was reversed. The subjects were trained in this Serial Discrimination Reversal procedure until successive acquisitions of the discrimination had stabilized. Drug treatments consisting of saline or 0.25, 1.0, 2.0, 4.0, 6.0 or 8.0 mg/kg of methylphenidate were then administered 20 min prior to the daily training sessions. Acquisition of the discrimination was enhanced by low doses of methylphenidate (1,2, and 4 mg/kg) and attentuated by higher doses (6 and 8 mg/kg).


Comparative effects of cocaine and pseudococaine on EEG activities, cardiorespiratory functions, and self-administration behavior in the rhesus monkey.

The effects of cocaine and pseudococaine on the EEGs, heart and respiratory rates, and self-administration behavior were studied in rhesus monkeys. An intravenous injection of cocaine (2.5 and 4.0 mg/kg) in the monkey produced low-voltage fast waves (LVFWs) in the EEGs and behavioral hyperexcitation accompanied by marked increases in the heart and respiratory rates with mydriasis and excessive salivation. In contrast, pseudococaine produced high-voltage slow waves (HVSWs) in the EEGs and behavioral depression accompanied by the same symptoms of the autonomic functions as those produced by cocaine. Both isomers were self-administered by the monkeys. During cocaine self-administration sessions, the animals showed hyperexcitation in their overall behavior, while with pseudococaine they showed almost normal behavioral responses. These results suggest that cocaine produced excitatory effects and pseudococaine inhibitory effects on the EEGs and behavior. Both isomers stimulate the heart and respiratory rates, and were self-administered by the monkeys.


Narcotic cuing and analgesic activity of narcotic analgesics: associative and dissociative characteristics.

By using a discrete-trial, two-lever, food-reinforced discrimination learning paradigm, rats were trained to discriminate the narcotic analgesic fentanyl (0.05 mg/kg) from saline. Stimulus generalization experiments with lower fentanyl doses (0.0025 to 0.02 mg/kg) were carried out to generate individual threshold doses. The latter were compared with the sensitivity of the same rats to the analgesic effect of fentanyl, and it was found that there is no correlation between these two sets of data. In a time-effect experiment, the duration of fentanyl's cuing effect was compared with that of its analgesic effect, and it was found that the time-effect characteristics of the narcotic cue are similar to those of analgesia. Again, however, there was no correlation between the duration of both effects within the same group of animals. The results further deliniate the associative and dissociative characteristics of the narcotic cue and narcotic analgesia.


The caloric and intoxicating properties of fluid intake as components of stress-induced ethanol consumption in rats.

Rats housed continuously in a test environment for 25 days were offered water, 5% v/v ethanol, 10% v/v ethanol, and propylene glycol at 7.5% w/v. The propylene glycol concentration represented a caloric midpoint between the 5 and 10% ethanol. After 10 baseline sessions, during which preference for the four solutions was shown to be statistically equal, shock schedules were introduced. The consumption of ethanol at both concentrations showed significant peaks for the interval immediately following 12 min of shock each hour. Intake peaks were not observed for the water or propylene glycol. Baseline blood alcohol levels were negligible, but blood levels under shock averaged 143 mg/dl and ranged from 45.0 mg/dl to 295.0 mg/dl. After the shock sessions were terminated, baseline drinking indicated no significant change in preference relative to pre-shock baselines. but there was an elevation in preference for 5% ethanol relative to the other fluids. The preference for propylene glycol or water did not change.


Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the 'cheese effect'.

After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.


Inhibition of phenylethanolamine-N-methyltransferase and brain-stimulated reward.

The centrally active inhibitors of phenylethanolamine-N-methyl transferase (PNMT; E.C. 2.1.1.28), the terminal enzyme for epinephrine biosynthesis in the brain, produced dose-related decreases in rats of responding for rewarding brain stimulation in adult male rats. Decreases occurred at dosages that did not produce measurable neurologic impairment. This suggests a possible role for central epinephrine-containing neurons in the maintenance of reward-mediated behaviors.


Lysergic acid diethylamide antagonizes shaking induced in rats by five chemically different compounds.

Thyrotropin-releasing hormone (TRH), sodium valproate, AF-3-5 (1-[2-hydroxyphenyl]-4-[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one), RX336-M (7,8-dihydro-5',6'-dimethylcyclohex-5'-eno-1',2',8',14 codeinone), and Sgd 8473 (alpha-[4-chlorobenzylideneamino)-oxy]-isobutyric acid) each induced repetitive shaking of the body of rats after intraperitoneal injection. This action of the five diverse chemicals appears to be subserved by a common pharmacological component, because pretreatment with d-lysergic acid diethylamide (0.03--1.0 mg kg-1, s.c.) attenuated the shaking behavior in a dose-related manner, and cross tolerance was found between RX336-M and TRH, sodium valproate, and AG-3-5.


Effects of ethanol on pregnant rats and their offspring.

Pregnant rats were intubated with either 1.0 or 2.0 g/kg of ethanol daily throughout gestation. Pair-fed vehicle-treated, and nontreated rats fed ad libitum, served as control groups for ethanol-treated animals. Ethanol treatment reduced food and water consumption and attenuated the gain in body weight of pregnant animals relative to nontreated animals fed ad libitum. Litter size, litter weight, and the mean weight per pup were reduced in both the ethanol-treated and pair-fed control groups. There was no evidence of gross malformations in any of the off-spring. Since the reduction in litter size and litter weights did not differ significantly between ethanol-treated and pair-fed controls, the effects of treatment with ethanol appeared to be related to a reduction in maternal intake of calories rather than to the direct effect of ethanol on the developing fetus. There were no significant differences between any of the groups of offspring on one-way shock avoidance learning, water maze escape learning, spontaneous alternation, or brightness discrimination learning in tests beginning at 75 days of age. Thus, at the doses of alcohol used in this study, there was no evidence of behavioral teratogenesis comparable to that reported for higher doses in animals or in man characterized by the fetal alcohol syndrome.


Blockade of photically induced epilepsy by 'dopamine agonist' ergot alkaloids.

The effect of the intravenous administration of ergot alkaloids on epileptic responses to intermittent photic stimulation )IPS) has been studied in adolescent baboons, Papio papio, from Senegal. Ergocornine, 1--2 mg/kg, produced marked autonomic and behavioural effects, slowed the EEG, and abolished myoclonic responses to IPS for 30--90 min. Ergometrine, 1 mg/kg, activated the EEG and blocked the induction of myoclonic responses for 1--3 h. Bromocriptine, 0.5--4 mg/kg, did not consistently prevent myoclonic responses to IPS. After pretreatment with a subconvulsant dose of allylglycine (180--200 mg/kg), lysergic acid diethylamide, 0.1 mg/kg, retained the capacity to block myoclonic responses to IPS, and ergocornine 1 mg/kg reduced such responses. The convulsant effect of allylglycine was enhanced, however, so that prolonged seizure sequences began 19--96 min after ergocornine administration. The protective action of ergot alkaloids against epileptic responses induced by sensory stimulation is interpreted in terms of effects at several sites, including dopaminergic and serotoninergic synapses.


A twin study on three enzymes (DBH, COMT, MAO) of catecholamine metabolism. Correlations with MMPI.

Ina a sample of 48 healthy adult male twin pairs (24 MZ, 24 DZ) the activities of DBH (serum),  COMT (red blood cells), and MAO (platelets) were determined. The twins had undergone a detailed psychodiagnostic test procedure before. Interindividual variability of enzyme activities is almost exclusively genetically determined. No correlation between enzyme activities within one subject is found. Correlations between enzyme activities and MMPI test scores were calculated. As in a comparable investigation by Murphy et al. (1977), negative correlations between MAO activity and MMPI scores prevailed.


Dopamine metabolites in human brain.

The relationship of human brain levels of 3,4-dihydroxyphenylacetic acid (DOPAC) to cerebrospinal fluid levels of this domapine (DA) metabolite was studied. The effect of postmortem delay was evaluated in the rat. DOPAC was resistant to postmortem changes in brain kept in situ. The level of DOPAC (free and conjugated) determined in DA-rich areas of six human brains amounted to only a fraction of the homovanillic acid (HVA) found in the same regions. The DOPAC/HVA ratio in human brain was similar to that found in CSF. We conclude that HVA is the major DA metabolite in human brain and that DA metabolite levels in CSF reflect DA metabolite levels in brain.


Haloperidol and lithium blocking of the mood response to intravenous methylphenidate.

The euthymic manic-d-pressive patients with therapeutic plasma lithium levels were each given two i.f. infusions of 30 mg of methylphenidate. The infusions were separated by at least 3 days. Before one infusion each patient was given 5 mg of haloperidol i.v. and before the other infusion each was given an identical volume of saline. A psychiatric observer was blind to the nature of the pretreatment and the order of pretreatment was randomized. Saline pretreated patients showed marked activation and euphoriant responses despite therapeutic lithium levels. Haloperidol pretreatment reduced this response in three patients and eliminated the euphoriant and activating response in the remaining seven patients. These results agree with the existence of a dopaminergic step in the induction of methylphenidate-induced activation and euphoria.


Brain and liver aldehyde dehydrogenase activity and voluntary ethanol consumption by rats: relations to strain, sex, and age.

Voluntary ethanol consumption and brain and liver aldehyde dehydrogenase (ALDH) activity were measured in male and female rats of the Tryon Maze-Bright (S1), Tryon Maze-Dull (S3), and Wistar strains. The levels of brain ALDH measured in the different groups, corresponded well to the levels of ethanol consumption, while differences in liver ALDH corresponded well to only the strain differences in ethanol intake. Within individual groups, levels of ethanol consumption correlated better with levels of brain and liver aldehyde-oxidizing capacity. Age affected both voluntary ethanol intake and liver ALDH levels, but there were no systematic relations between the two effects. Age did not significantly affect the cerebral-aldehyde oxidizing capacity. It is argued that inherent variation in brain ALDH activity may be a principal biochemical counterpart of the differences in ethanol intake amoung different strains and sexes of laboratory rats.


Radiotherapy in marginal resectable and non-resectable rectum cancer.

66 patients with inoperable rectum cancer were treated with megavoltage irradiation. These patients were studied in order to see if high dose radiotherapy could cure inoperable patients. No patients were cured. The palliative effect was important, because in most patients a colostomy was avoided. 21 patients with marginal resectable rectum cancer received preoperative irradiation. The effect of combined therapy in this highly selected group of patients gives an indication for a 50% 5-year cure rate.


Improving performance by multiple interpretations of chest radiographs: effectiveness and cost.

The accuracy and cost of four methods of duplicate reading were evaluated. Eight radiologists interpreted 100 random chest radiographs. Using a third independent interpretation to resolve disagreements between pairs of readers ("Pseudoarbitration") was the most effective method overall, reducing errors 37%, increasing correct interpretations 18%, and adding 19% to the cost of an error-free interpretation. Resolving disagreements in facor of positive diagnoses was the best method for reducing omissions, but it almost doubled false-positive diagnoses. The choice between single and multiple interpretations must be evaluated in each clinical setting and should consider expected improvements in accuracy, implications for patient care, and additional costs.


Computed tomography in a private practice office.

Since 1975, the author examined over 6,000 outpatient and hospital inpatients with computed tomography in a private practice CT office. The patients were referred by 368 physicians and 26 hospitals. A CT center in a private radiology office available for immediate utilization by several hospitals and many physicians is an effective method of controlling costs and containing unnecessary capital equipment expenditures, and contributes to the preservation of the private practice of radiology and medicine.


Variations in depth-dose data between open and wedge fields for 4-MV X-rays.

Central-axis depth-dose data for 4-MV x rays, including tissue-maximum ratios, were measured for wedge fields. Comparison with corresponding open-field data revealed differences in magnitude which increased with depth, field size, and wedge thickness. However, phantom scatter correction factors for the wedge fields differed less than 1% from corresponding open-field factors. The differences in central-axis per cent depth doses between the two types of fields indicate beam hardening by the wedge filter. This study also implies that the derivation of tissue-maximum ratios from central-axis per cent depth is as valid for wedge as for open fields.


Improved technique for obtaining teletherapy portal radiographs with high-energy photons.

H & D curves were obtained for various film/screen combinations exposed to 60Co, 4-MV, and 45-MV photons. Data indicate that contrast is enhanced more by light-emitting screens than by lead screens or direct exposure. Flexible film cassettes are more comfortable for the patient, and extra-large film can be used for larger patients.


Primary treatment of carcinoma of the lower rectum and anal canal by a combination of external irradiation and interstitial implant.

Ten patients with carcinoma of the anorectum were treated with a combination of external irradiation and after-loading interstitial 192Ir implant, which seems to be effective in controlling relatively small cancers of the anorectum and providing effective palliation of extensive lesions. Five of the 10 patients remain free of tumor after a minimum follow-up of 15 months. Four of the 10 were treated with one interstitial implant and 4,000--5,000 rads of external irradiation and 6 were treated with the same amount of irradiation and two implants. When two implants were used, complications were minimal.


A comparison of the effects of 50 MeVd leads to be neutron and cobalt-60 irradiation of the kidneys of rhesus monkeys.

Twenty rhesus monkeys had one kidney irradiated (after undergoing unilateral nephrectomies) with one of four doses: 960 or 1080 rads of 50 MeVd leads to Be neutrons, or 2350 or 2700 rads of 60Co. Whereas animals treated with the lower dose of neutrons or 60Co are alive with relatively normal renal function, those treated with the higher dose of neutrons died of radiation nephritis. Animals treated with the higher dose of 60Co developed radiation nephritis but survived. The physiological and histopathological changes of radiation nephritis secondary to neutron irradiation are not qualitatively different from those reported for radiation nephritis secondary to photon irradiation.


Risk factors in complications of aqueous myelography.

The adverse reactions from aqueous myelography in 88 primates were reviewed to determine what factors increase the risk of complications. Seventy-four iocarmate (Dimeray) myelograms were obtained on 41 animals, and 90 metrizamide (Amipaque) myelograms were obtained on 47 animals. The risk of seizures and death from iocarmate myelography was higher than from metrizamide myelography. In animals that had previous myelograms or showed evidence of arachnoiditis, the risk of complications from aqueous myelography was higher. Additional precautions may be indicated if aqueous myelography is performed in patients with arachnoiditis.


Dosimetry for tangential chest wall irradiation.

The skin-sparing effect of megavoltage photons is lost to a varying extent when tangential beams are used to irradiate the chest wall. The skin dose for this technique, with and without a bolus, was investigated for 4- and 6-MV photons using film, thermoluminescent dosimeters, and an ionization chamber. Metal/tissue interface effects were observed when a flexible brass fabric material was used as a bolus.


Total-body irradiation with 25-MV photons in advanced non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Preliminary results and complications.

Patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma were treated with total-body irradiation (TBI). One group was treated after chemotherapy failed, while the other group received TBI initially. TBI was ineffective against CLL after chemotherapy failed. All patients with lymphocytic lymphoma who initially responded to chemotherapy but later relapsed were helped by TBI, as were 88% of patients with previously untreated lymphocytic lymphomas.


Decreased smooth muscle side effects with 16, 16-dimethyl-trans-delta2-PGE1 methyl ester in Japanese monkey (Macaca Fuscata Fuscata).

The smooth muscle stimulating activity of a new PGE1 analog, 16, 16-dimethyl- trans delta2 -PGE1 methyl ester (ONO-802) was evaluated by simultaneously recording the EMG of the uterus and intestines, along with urinary bladder pressure, and blood pressure in pregnant and non-pregnant Japanese monkeys (Macaca fuscata fuscata). Single intravenous injections of ONO-802 in increasing dosages (0.2-5 microgram/kg) were found to be 50-100 times or more effective in inducing uterine contraction than PGF2alpha and PGE1. A mild, transient gastrointestinal muscle stimulating activity was observed, but change in urinary bladder pressure and blood pressure was not evident. ONO-802 induced uterine contractions in the pregnant animals were 10 times greater than in the non-pregnant animals. These results suggest that ONO-802 may be a suitable clinical prostaglandin for use in therapeutic abortion.


Dithiothreitol inactivation of frog epidermis tyrosinase.

Frog epidermis tyrosinase inactivation by dithiothreitol (DTT), both in the proenzyme and active forms, have been studied. Upon increasing DTT:enzyme-up to 1o(6):1 ratios and depending on the incubation period, two inactivation steps both in proenzyme and enzyme were observed. Enzyme lost its activity faster than proenzyme. Oxygen favoured inactivation. After dialysis of the DTT:protein (10(6):1) incubation medium, 20% of the original enzyme activity was recovered. However it decreased to 15% if the enzyme had been incubated with substrate. Conformational changes due to loss of activity were not shown on the fluorescence spectra.


Absorption, tissue distribution and excretion of 14C ethylenethiourea by the rhesus monkey and rat.

Two female rhesus monkeys and four Sprague-Dawley rats were give 14C ethylenethiourea by gastric intubation and the rate of excretion was evaluated for 48 hours. The animals were subsequently sacrificed and the tissue distribution of 14C determined. The major route of 14C excretion was by way of the urine with 47 and 64% of the total radioactivity in the monkey urine and an average of 82% in the rat urine. The feces accounted for less than 1.5% of the radioactivity in both animal species. Tissue distribution accounted for 21 and 28% of the administered 14C in the monkey, while less than 1% was located in the rat tissues. The skin and musculature contained the largest amount of radioactivity in both species.


Some response characteristics of CO2 electrodes.

Radiometer carbon dioxide electrodes and probably other electrodes of similar design do not give the same readings, except under certain very limited conditions, when used to measure carbon dioxide concentrations in solution and the gas phase with which the liquid is in equilibrium. Blood samples of high P(CO2), when introduced into the sample chamber of an electrode at low P(CO2), lose CO2 to the electrode resulting in a reduction of sample P(CO2) and hence, because the sample size is very small, a recorded value much below the real P(CO2) of the sample is obtained. The reverse occurs if the P(CO2) of the sample is below that of the electrode. To avoid these problems the electrode should be held at the same P(CO2) as the sample, or sample replacement should be used to establish the real P(CO2). The differences in response of the electrode to gases and liquids should also be taken into account.


[Lafora disease (author's transl)].

On the basis of 21 personal observations as well as those (82) from the litterature, it is concluded that the progressive myoclonic epilepsy with Lafora bodies (P.M.E.) constitutes a disease on its own. The clinical features are those described in the litterature observations and completed by some characteristics; the high frequency of visual symptoms (47 p. 100 personal cases); the relatively less bad evolution of epilepsy, perhaps in relation with use of modern drugs; the relatively moderate intensity of myoclonus which becomes complete only at the end of the evolution. From E.E.G. point of view, we can distinguish three periods: an initial one at the very onset of disease, who will show the same features as observated in primary generalized epilepsy, i.e. a well preserved background activity with superimposed generalized fast spikes and waves facilitated by the I.L.S. Then follows a period of evolutive E.E.G. (1-2 years after the onset of the disease) characterized by progressive slowing of the posterior background, enlargement of posterior slow activity and appearance of diffuse theta and delta activity. Simultaneously spikes and waves are taking less typical and bisynchronous aspect. Finally after 3 to 5 years from the onset there is a diffusely slow E.E.G. with superimposed fast multiple spikes. The E.E.G. findings in litterature usually refer only to this last period (stationary or terminal period). Occipital independent multiple spikes are frequently observed and could correlate with the visual symptoms observated in the Lafora disease. Some elements of differential diagnosis are given with respect to primary generalized epilepsy at the onset of the disease and later on with respect to dyssynergia cerebellaris myoclonica and to the progressive myoclonic epilepsy without Lafora bodies.


[Clinical and electrophysiological aspects of the gangliosidoses (author's transl)].

The gangliosidoses belong to the family of diseases known as the lipidoses and are due to an excess of ganglioside I (GM1) or II (GM2). The illness described by Landing belongs to Group I, whilst Tay-Sachs and Sandhoff's disease are type 2. This study was particularly concerned with the electro-clinical aspects of group 2, and 4 stages have been differentiated: --the first occurs between 4-10 months: the child is apathetic, hypotonic and has occasional audiogenic seizures; fundoscopy revealing the classical cherry red spot on the macula. The diagnosis can be confirmed by biopsy. The EEG is irregular but abnormalities are minor. --the second stage (10 months-2 years) the child spastic and amaurotic, often unresponsive is suffering from frequent seizures. The EEG is of high voltage, with slow and sharp waves. Auditory stimulation does not produce EEG changes. --in the third and 4th stages (after 2 years) the child is in a vegetative state with a progressive reduction in EEG voltage and sharp waves until death aged 3 or 4. Although there is a good correlation between clinical signs and EEG this is of no diagnostic value.


Studies on the determination of plasma prolactin.

A double antibody solid-phase (DASP) and a plyethylene glycol (PEG) radioimmunoassay method for plasma prolactin determination were developed and evaluated as to their reliability. The iodination of prolactin was carried out using a lactoperoxidase sorbent with iodination conditions being optimized by studying the effect of reaction buffer pH in the range 5.0--7.0 at two ionic strengths. With the DASP-technique, intra-assay coefficient of variation was 6% (n = 30) and the inter-assay coefficient of variation 12% (n = 12), and with the PEG-technique, intra-assay coefficient of variation was 10% (n = 10). The sensitivity, with the DASP system, was 0.098 ng/tube and the detection limit for plasma, 0.8 microgram/l. The use of the PEG-technique was abandoned because of poor precision and nonparallelism of plasma dilution curves with the standard curve. The whole mean basal plasma value was 34.0 +/- 19.5 microgram/l (mean +/- 2SD, n = 35). The response after administration of 200 mg sulphiride was an increase of between 119--220% of basal values and after administration of 100 mg of chlorpromazine, an increase of 85--140%. After administration of TRH (thyrotropine releasing hormone) an increase of between 60 and 330% was obtained, the mean increments after 20 min in outpatients being 87.0 microgram/l and in hospitalized subjects, 51.2 microgram/l.


Purification and immunochemical quantitation of human pancreatic secretory trypsin inhibitor.

Human pancreatic secretory trypsin inhibitor has been purified from pancreatic juice obtained on connection with surgery in the pancreas. The purification was accomplished by gel filtration on Sephadex G-75 and ion-exchange chromatography on SP-Sephadex C-50 giving 49% yield. Five forms of the inhibitor were demonstrated by combined chromatographic and electrophoretic methods. On gel filtration the inhibitor was shown to have the same molecular weight as the Kunitz inhibitor, i.e. about 6500. Inhibitor purified by affinity chromatography on trypsin-Affi-Gel 10 was used for stimulating antiserum production in rabbits. The antiserum was used for immunochemical quantitation of the inhibitor by means of Mancini's single radial immunodiffusion method alone or in combination with a more sensitive double antibody technique followed by autoradiography. It was possible to measure concentrations of inhibitor as low as 1.5 mg/l and 0.2 mg/l using these methods.


Surface immunoglobulin of human lymphocytes.

Using ferritin as surface marker, the localization of the surface immunoglobulin (Ig) was studied on peripheral lymphocytes from normal human individuals and patients with macroglobulinaemia Waldenström by scanning immunoelectron microscopy. Normal IgG-, IgM-lymphocytes and pathological IgM-lymphocytes were then compared with regard to their topographical differences. In all cells examined, IgG- and IgM-conjugated ferritin particles were detected all over the cell surface, but the distribution of the former on the normal IgG-lymphocytes was slightly more diffuse than that of the latter on the normal and pathological IgM-lymphocytes. Furthermore, in the pathological IgM-lymphocytes, the clustered IgM-conjugated ferritin particles were found in great number on the microvilli. Normal IgG-lymphocytes were almost always characterized by short rod-like microvilli standing densely and vertically on the cell surface. Some of normal IgM-lymphocytes had a similar appearance to those of normal IgG-lymphocytes (type A) but others (type B) had tilted rod-like microvilli or wide plate-like processes on their surface. As for IgM-lymphocytes of macroglobulinaemia, most lymphocytes had tilted rodlike mirovilli and wide plate-like processes similar to type B, whereas a minor population of the pathological lymphocytes carried long, thin rod-like microvilli standing vertically on the surface.


Immunochemical assays for an early diagnosis of endemic nephropathy.

Comparative studies aiming at the detection of certain tubular protein elements by means of Ouchterlony's immunodiffusion, in parallel with lysozyme and guanase assays, were carried out in the unconcentrated urines of 746 subjects, of whom 655 apparently healthy inhabitants (mostly children) from a region with endemic nephropathy (EN) and from Bucharest, as well as 91 adults with EN or various other diseases with renal involvement. The presence of light chains, of lysozymuria exceeding 2 microgram/ml, of beta2 microglobulin and of guanase in the urines of children and adults from the endemic area was significantly more frequent than in the control groups. These immunochemical changes are hence considered as valuable criteria for the detection of EN prior to the uremic stage. They should be looked for, first and foremost, in the young relatives of patients with this disease. In the stage of nitrogen retention the diagnostic value of these tests is reduced, since the same changes can also be found in the urines of patients suffering from other diseases with renal involvement, which show nitrogen retention as well.


Excitation-contraction coupling in skeletal muscle: blockade by high extracellular concentrations of calcium buffers.

High concentrations (80 to 90 millimolar) of the calcium buffers EGTA and citrate (less than 10(-7) molar free calcium ion) reversibly block excitation-contraction coupling in intact frog skeletal fibers, but do not block caffeine-induced contractures. Solutions containing the same free calcium concentration but lower concentrations of calcium buffer (1 millimolar) do not block excitation-contraction coupling. These results suggest that excitation-contraction coupling requires the presence of calcium in a "protected" extracellular compartment, probably the transverse tubular network, and that calcium is actively transported into this compartment from the muscle cell cytoplasm.


Malignant neoplasms of genetic origin in Drosophila melanogaster.

Malignant neoplasms that develop in 12 recessive-lethal, larval mutants of Drosophila melanogaster are discussed. These mutations affect the adult optic neuroblasts and ganglion-mother cells in the larval brain, the imaginal discs, and the hematopoietic organs. The malignant neoplasms exhibit fast, autonomous growth, loss of the capacity for differentiation, increased mobility and invasiveness, lethality in situ and after transplantation, and histological, fine structural, and karyotypic abnormalities. Intermediate neoplasms are also found. These combine both benign and malignant qualities. They grow in a noninvasive, compact fashion, typical of benign tumors, yet they also exhibit malignant qualities such as fast, autonomous, and lethal growth, loss of differentiation capacity, changes in cellular morphology, and lethal growth after transplantation into wild-type hosts. Thus Drosophila and vertebrate neoplasms show striking similarities.


Thermorestoration of mutagenic radiation damage in bacterial spores.

The frequency of mutations in Bacillus subtilis spores irradiated anoxically with ionizing radiation decreased as a result of subsequent anoxic heating to the same extent as the increase in spore survival. This result indicates that DNA damage is the origin of the "thermorestoration" phenomenon.


Chronic focal epileptiform discharges induced by injection of iron into rat and cat cortex.

A single injection of 5 or 10 microliters of ferrous or ferric chloride into rat or cat sensorimotor cortex resulted in chronic recurrent focal paroxysmal electroencephalographic discharges as well as behavioral convulsions and electrical seizures. Recurrent focal epileptiform discharge caused by cortical injection of iron salts suggests that the development of human posttraumatic epilepsy may depend, in part, on the neurochemical alterations induced by the principal metallic ions found in whole blood.


Light-stimulated morphogenesis in the fruiting myxobacterium Stigmatella aurantiaca.

When the fruiting myxobacterium Stigmatella aurantiaca, a gliding prokaryote, is starved on an agar surface, the cells form multicellular aggregates resulting from morphogenetic movements. In the presence of incandescent light, each aggregate develops into a structurally complex fruiting body, possessing a stalk and several sporangia. In contrast, this pattern of development is not seen when cultures are incubated in the dark. The cells form irregular interconnecting aggregates, which rarely develop into fruits. However, aggregates formed in the light will develop into fruits even if placed in the dark, suggesting that the light produced a relatively stable alteration in the phenotype of the cells.


Abnormal auditory evoked potentials in early infancy malnutrition.

Computer-averaged auditory evoked potentials were found to be abnormal in infants hospitalized because of severe malnutrition (marasmus). They improved as the infants' somatic growth improved during the course of treatment, but were still deviant at the time of discharge from the hospital and at subsequent outpatient follow-up. Abnormalities in evoked potentials may reflect a long-lasting effect of malnutrition on brain function.


Suid evolution and correlation of African hominid localities: an alternative taxonomy.

New phylogenies were recently proposed by White and Harris, who recognized 7 genera and 16 species of fossil and extant suids from sub-Saharan Africa. This scheme is regarded here as oversimplified and an alternative is suggested, in which 9 genera and 21 species are recognized. The taxonomic and phylogenetic differences do not have any significant effect on the stratigraphic interpretations offered by White and Harris.


Choice behavior in rhesus monkeys: cocaine versus food.

Rhesus monkeys were allowed to choose between intravenous injections of cocaine and food reinforcement for lever pressing. A choice trial was available every 15 minutes continuously for 8 days. The animals chose cocaine almost exclusively, which resulted in high cocaine intake, decreased food intake, weight loss, and marked behavioral toxicity. The study provides evidence of the reinforcing efficacy of cocaine.


Vasectomy increases the severity of diet-induced atherosclerosis in Macaca fascicularis.

Diet-induced atherosclerosis developed more extensively in vasectomized cynomolgus monkeys (Macaca fascicularis) than in sham-vasectomized control monkeys fed the same diet. The effect was most pronounced in the abdominal aortas, carotid arteries, distal segments of the coronary arteries, and intracranial cerebral arteries. Antibodies to sperm developed in all vasectomized monkeys, and complement and immunoglobulins were associated with atherosclerotic plaques in some of the vasectomized animals. The immunological response to sperm antigens that often accompanies vasectomy may exacerbate atherosclerosis.


Admission screening for hepatitis B surface antigen in a university hospital.

Upon admission to the hospital, 7,984 patients were tested for hepatitis B surface antigen (HBsAg) by radioimmunoassay. Seventy-one patients had sera positive for HBsAg. Twenty-four (34%) were possible asymptomatic carriers in whom liver function was not further evaluated and occult liver disease could not be excluded: 16 (23%) had either a previous history or admitting diagnosis of hepatic dysfunction; eight(11%) had occult liver disease, revealed after HBsAg antigenemia was discovered; and 25 (34%) were unsuspected asymptomatic carriers whose liver function was normal. We concluded that screening for HBsAg was an effective preventive tool in identifying HBsAg-positive patients. Screening solely for the detection of occult liver disease is not an effective method because of the high cost. Perhaps because of the unsolicited nature of this data collection, screening for HBsAg was not clinically effective for the majority of patients, as evidenced by the high incidence of inadequate clinical evaluations and lack of serologic follow-up. Proposals to alleviate ineffectiveness are discussed.


Multivalvular vegetations in a patient with enterococcal endocarditis diagnosed by echocardiography.

A patient with enterococcal endocarditis of 11 months' duration is presented, and the role of surgery and echocardiography is reviewed. Echocardiography revealed vegetations of the aortic and mitral valves. After appropriate antibiotic therapy the patient had successful aortic and mitral valve replacement with porcine heterografts. Enterococcal endocarditis is increasing in frequency and is likely to infect young women of childbearing age, elderly men who have had genitourinary tract manipulation, and abusers of intravenous drugs. Aortic and mitral valves are most frequently affected, cardiac failure is common, and often no evidence of underlying heart disease can be found. The use of echocardiography in this patient provided accurate diagnosis of valvular vegetations and assessment of the hemodynamic severity of the lesion, thus preventing the need for cardiac catheterization and its potential risk of septic embolization.


Chronic peritoneal dialysis in a patient with primary amyloidosis, renal failure, and factor X deficiency.

Chronic peritoneal dialysis was used in a patient with renal failure due to primary amyloidosis. Paraprotein was demonstrated in serum and urine, and was removed in peritoneal dialysate. The patient objectively improved as long as he was receiving peritoneal dialysis. When dietary indiscretion necessitated hemodialysis for fluid removal, he died shortly thereafter of subdural hematomas, possibly aggravated by factor X deficiency. Reasons for selecting chronic peritoneal dialysis as the treatment of choice in patients with renal failure associated with overproduction of paraprotein are discussed.


The occurrence of Candida in hospital patients and normal subjects.

The distribution of different Candida species and different serogroups of C. albicans have been analysed. C. albicans is by far the most predominant species isolated from all clinical specimens. Group A of C. albicans was isolated 10 times more frequently than group B strains from patients who had respiratory infection and 4.4 times more frequently from those who had other clinical conditions. However, both serogroups were isolated at comparable frequencies from the genitals. In the instances where repeated isolation were made, colonization by one serogroup often occurs to the exclusion of the other serogroup and species. Thus, it was frequently observed that individual patients often gave repeated isolation of one serogroup of C. albicans only. These findings are of obvious diagnostic relevance and may facilitate the evaluation of possible clinical significance of laboratory studies.


Enostosis of the spine.

Five patients with single sclerotic vertebral body lesions had serial radiographs demonstrating no change in size of the radiodensities. Radionuclide bone imaging, obtained in 4 of these patients, showed no increased radioisotopic uptake in the areas in question. The absence of growth of the lesions on follow-up radiographs and the presence of negative bone scans support the diagnosis of enostoses of the spine. It is important for the radiologist to realize that benign sclerosis of a single vertebral body may simulate skeletal metastasis.


Cell fusion between temperature-sensitive mutants of a Drosophila melanogaster cell line.

Temperature-sensitive (ts) mutants were isolated in a cell line of Drosophila melanogaster, GM1, by ethyl methanesulfate treatment. Two of them, ts15 and ts58, formed colonies at 23 degrees C but not at 30 degrees when inoculated at densities of/or less than 10(5) cells per 60 X 15-mm dish. By using these ts mutants, cell fusion was attempted with polyethylene glycol (PEG) 6000. Several colonies per dish developed at 30 degrees C when different ts mutants were mixed, treated with PEG, and inoculated at a density of 10(4) cells per dish. Cells in some of the colonies thus developed were propagated and their temperature-sensitive character and karyotypes were studied. The results indicated that cell fusion could be induced with PEG and that the cells which formed colonies at 30 degrees C after PEG treatment were the hybrids in which the temperature-sensitive lesions in the mutants were complemented.


The interneural incision for biliary tract operations.

The interneural incision has clearly been demonstrated to be efficient, being executed rapidly and providing excellent exposure to the right upper abdominal quadrant. The postoperative period is marked by less subjective complaints; decreased narcotic requirements, and increased ease of walking, coughing and deep breathing. The result is improved pulmonary toilet and a negligible incidence of pulmonary complications. At long term observation, there is a scar which is cosmetically preferable, without neuroma or hernia formation and with no complaints of numbness or paresthesias in the area of the incision. For all these reasons, we have concluded that the interneural incision is superior, in the appropriate anatomic situation, than is either a vertical or subcostal incision for biliary tract operations.