Effect of bases and accelerants on the anti-inflammatory activity of topical corticosteroids.

The use of measurement of skin thickness in guinea pigs has been compared with other techniques for assessment of topical applications. This method has provided us with an accurate evaluation of the corticosteroid dose-response curve and the effect of bases. The method has shown that non-steroid prostaglandin synthesis inhibitors can also be demonstrated to possess topical anti-inflammatory activity. As expected, indomethacin acts synergistically when formulated with hydrocortisone. Contrary to our expectation, both salicylic acid and acetylsalicylic acid show antagonism with hydrocortisone. This finding may be of clinical significance. We have also found that a combination of salicylic acid and indomethacin produces striking inflammatory changes in guinea pig skin which points to interaction of these two drugs in the guinea pig. The relevance of this phenomenon to both the mode of action of the two drugs and their use in clinical practice remains to be elucidated, but preliminary tests suggest that similar changes take place in human skin.


Vasoconstriction in response to corticosteroids observed in human lips.

Following epimucous application of corticosteroids on the lips, narrowing and shortening of the terminal network of vessels occurs within 5-7 min. The decrease in infrared radiation needs a few more minutes. Contrary to the application of epinephrine-like substances, the change of the vessels occurs first in the superficial layers and only later on in the deeper layers. In addition to the effect on the muscles of the vessels, a narrowing of the capillaries can also be influenced by the effect of corticosteroids on the endothelial cells. Changes of the ground substance of the capillary vessel bed are also a possibility.


Thyroid thermogenesis: minimal contribution of energy requirement for protein synthesis.

Cycloheximide (5.0 mug/ml) had no significant effect on respiration of liver slices prepared from euthyroid rats (i.e., QO2 of 15.5 +/- 0.8 vs. 14.9 +/- 0.8 mul/mg protein) despite an 83.8 +/- 2.1% inhibition of protein synthesis as judged by [3H]leucine incorporation into the trichloroacetic acid precipitable fraction. Injection of triiodothyronine increased the QO2 of rat liver slices to 22.6 +/- 1.1 mul/h/mg protein. The QO2 of hyperthyroid slices remained high in the presence of cycloheximide although protein synthesis was inhibited by 84.4 +/- 2.0%. These results imply that the energy requirement for protein synthesis contributes little to QO2 of euthyroid liver and does not account for a significant fraction of the increase in hepatic QO2 obtained in the transition from the euthyroid to the hyperthyroid state.


Dynamics of steroid uptake in rat testis studied by quantitative autoradiography.

Localization of radioactive steroids in rat testis was studied by autoradiography of tissue section. For autoradiography small tissue samples were frozen, freeze-dried under vacuum, fixed with osmium vapor and embedded in epon. The transfer of radioactive steroids was studied after in vitro perfusion of radioactive steroids in the testes isolated from hypophysectomized animals, thereby excluding the interference of endogenous steroids. Quantitative autoradiography on the basis of grain densities after perfusion of testes with tritiated pregnenolone or testosterone, revealed an accumulation of the label in the Leydig cell cytoplasm. After longer perfusion periods the amount of label in the seminiferous tubules increased and a preferential localization was observed in the basal cytoplasm of Sertoli cells and in lipid droplets. Perfusion of testes with estradiol-17 beta resulted in a distinctly different pattern of radioactivity in the autoradiographs. A high labeling of the Leydig cell nuclei was observed in combination with a low general labeling of all the other cell structures. The results suggest that different steroids are localized in different specific areas of the rat testes in vivo.


Transport of thyroglobulin and peroxidase in the thyroid follicle cell.

The purpose of this study was to explore the nature of the protein(s) in the exocytotic vesicles in the thyroid follicle cells and to ascertain whether or not thyroglobulin and peroxidase are transported by the same vesicles through the apical region of the cells to the follicle lumen. The study was performed on rats pretreated with thyroxine for 2 days in order to inhibit endocytosis. A fraction of exocytotic vesicles was isolated by centrifugation in continuous and discontinuous sucrose density gradients. The protein content of the vesicles were analysed by electrophoresis in continuous polyacrylamide gradient gels. The vesicles contained (uniodinated) thyroglobulin, 12-S protein and thyralbumin. Parallel histochemical studies in the electron microscope. These observations have important bearings on the mechanisms for thyroglobulin iodination, since it has been demonstrated that iodination does not occur in the exocytotic vesicles but in connection with the opening of the vesicles at the apical cell surface.


Hormonal control of vitellogenin synthesis in avian liver.

Estradiol induces the synthesis of vitellogenin in the avian liver. We describe the precursor-product relationship between vitellogenin and the yolk proteins phosvitin and lipovitellin. The high rate of vitellogenin synthesis is a consequence of the accumulation of a stable messenger RNA. We suggest that estradiol acts at the level of the genome by opening a hitherto non-transcribed gene.


Effect of prolactin on vitamin D metabolism.

The effect of ovine prolactin on the renal 25-hydroxycholecalciferol-1-hydroxylase was studied in the chick. Prolactin was found to increase the activity of this enzyme in both long-term and short-term experiments. In the long term, 7 days treatment with prolactin caused a marked stimulation of the 1-hydroxylase activity, however this effect was only seen when the enzyme was assayed 2-3 hours after the final injection of prolactin. A single subcutaneous injection of prolactin was also effective in increasing the 1-hydroxylase activity, this effect was maximal at one hour and had largely disappeared 3 hours after prolactin administration.


RNA synthesis in different stages of rat seminiferous epithelial cycle.

In vitro RNA synthesis has been analyzed using autoradiographic and electrophoretic methods in isolated 1-2 mm segments of rat seminiferous tubules. The cellular composition of each segment was accurately identified using microscopic analysis of the transillumination pattern of the freshly isolated, unstained, seminiferous tubules combined with phase-contrast microscopy of the living spermatogenic cells. The RNA synthesized in the seminiferous tubules was found to be mostly heterogenous nuclear RNA (HnRNA), which appeared to have a long lifetime. It was most actively formed in the stages which contain mid-pachytene spermatocytes. Formation of rRNA was slow in all stages and it was first observed when a 2-h pulse with [3H]uridine was followed by a 6-h chase. A very low RNA synthetic rate was observed in the stage containing the meiotic reduction divisions. The function of the meiotic RNA in regulation of spermiogenesis is discussed.


Uptake of biogenic amines by thyroid glands.

The biogenic amines, serotonin (5-HT) and norepinephrine, activate follicular cells and are endogenous thyroid constitutents. Both amines are taken up by throid lobes incubated in vitro. Uptake of 5-HT is temperature and concentration dependent, is inhibited by chlorimipramine more than by desmethylimipramine, and although it is inhibited by norepinephrine, 5-HT uptake is unaffected by chemical sympathetomy with 6-hydroxydopamine. Electron microscopic radioautography reveals that follicular cells are responsible for uptake of 5-HT and adrenergic nerves for uptake of norepinephrine. These data are consistent with the hypothesis that biogenic amines are intrathyroidal transmitters acting on follicular cells, and that uptake mechanisms may contribute to their inactivation.


Induction of avidin in the chick oviduct by tissue damage. Effect of promethazine chloride, CaCl2 and hydrocortisone on local induction.

The local effect of the mechanical induction of avidin by ligature was studied in diethylstilbestrol-primed chicks. The highest induction of avidin was always found in the immediate vicinity of the silk ligature of the oviduct. The locality of the induction was highly dependent on the position of the ligature. The nonligated parts of the ligated oviduct also showed a slight avidin induction. These results indicate a strictly local effect of avidin induction by ligature. An antihistamine, promethazine chloride, has a potentiating effect on the avidin induction by ligature when administered after the ligature. On the other hand, membrane stabilization by hydrocortisone or CaCl2 did not influence the ligature-induced avidin synthesis. On the basis of these results it is concluded that the avidin induction is not mediated by histamine activation or membrane damage.


Chemical composition of porcine thyroid cell plasma membranes.

Plasma membranes were isolated from thyroid cells obtained by trypsinization of porcine glands and maintained in culture conditions in the presence or absence of thyrotropin or dibutyryl cyclic AMP. The protein, phospholipid, cholesterol and sialic acid content of the 3 types of cell plasma membranes were very similar. High cholesterol and sialic acid content characterized these membranes. The amino acid and carbohydrate composition was similar to that shown for other eukaryotic plasma membranes. Sodium dodecylsulfate-polyacrylamide gel electrophoresis disclosed the presence of more than 20 protein bands, of which six corresponded to glycoproteins.


Possibilities of immunization against cholera and related enterotoxic enteropathies.

Scientifically controlled field studies have established that parenterally administered killed vibrio vaccines or somatic antigen preparations offer only limited degrees of protection in certain population groups and have  made it obvious that new approaches to the immunoprophylaxis of cholera are needed. It has now also been established that the symptoms of cholera result from the action of the cholera enterotoxin (choleragen) on the epithelial cells of the small intestine.  Immulogically related enterotoxins have been incriminated in other newly recognized diarrheal diseases (e.g., those caused by Escherichia coli and "non-agglutinable" (NAG)vibrios). Additionally, volunteer studies have shown that induced cholera results in rather solid and lasting immunity against homologous re-challenge thus proving that immunity against cholera is feasible. Although numerous studies have demonstrated the efficacy of purely antitoxic immunity in experimental animal models, the protective effect of parenterally administered glutaraldehyde treated toxoid in man has shown to be limited, at best. The protection attained following an attack of cholera suggests that local immune  mechanism may be of predominant importance. Immunity has  been stimulated, experimentally in mice, by toxin antigen administered per os on a single occasion. Choleragenoid, which is non-toxic but binds to the same receptors as cholera toxin, has been shown to provide immediate resistance as well as later immunity to toxin challenge. More ideal, however, would be a colonizing mutant of V. cholerae which elaborates a non-toxic cross-reactive material (CRM) like choleragenoid and which could stimulate local antitoxic as well as anti-vibrio immune mechanisms. A tox-mutant of V. cholerae which is avirulent for man has been shown to elicit substantial immunity in man but the ideal CRM-mutant has yet to be found.


Influenza.

The author reminds us of the significance of hemagglutinin and neuraminidase, as well as their respective antibodies, in the development of influenza in man and other organisms. These factors are certainly not the only ones responsible for clinical symptomatology. The value of killed or attenuated virus vaccines is then discussed, together with the application of the viruses at the portal of entry, antigenic recombinants and particularly the elaboration of a "master strain" of virus (for example "Alice", WRL 105). Particular attention is devoted to the ts mutants, their genetic stability, transmissibility and protecting power against wild strains. The virus which Chanock and his associates have developed during the last few years offers considerable advantages; nevertheless continued research by several teams is suggested in order to improve still further the qualities of this virus.


Pathogenicity, immunogenicity and genetic stability in mice and ferrets of a cold inhibitor-resistant mutant of influenza H3N2 virus.

A cold inhibitor-resistant mutant was derived from MRC-2 virus by means of serial passages in the presence of rabbit serum and at gradually decreasing temperatures. This virus, denoted MRC-2 IRc, grew well at both 26 and 37 degree C. The pathogenicity and immunogenicity of the virus was examined in mice and ferrets. No clinical reactions were detected in either species. Both mice and ferrets developed high levels of hemagglutination inhibition and neuraminidase inhibition antibodies. The virus was reisolated from the lungs of intranasally inoculated mice; in ferrets it was recovered from nasal washing and trachea but not from lungs. The properties of the isolated viruses were examined. The viruses reisolated from mice lost their reproductive capacity at 26 degree C and were less resistant to inhibitors than the original virus. The virus isolated from the ferret nose was identical with the original virus, however the tracheal isolate exhibited a certain degree of reversion in both the markers tested.


Preparation and characterization of live recombinant influenza vaccine.

Strain WRL 105 was prepared by recombination between the A/Finland/4/74 (H3N2) and attenuated A/Okuda/57 (H2N2) strains by a method previously described. A single intranasal dose of WRL 105 strain live attenuated influenza vaccine was administered to volunteers at three dose levels and homologous serum antibody titres and virus excretion were monitored. Doses greater than 10(6.3)EID50 gave 4-fold or greater increases in antibody titre in 80% of seronegative volunteers.


Recombination of influenza A virus strains: effect on pathogenicity.

Influenza viruses can recombine genetic information, and progeny virus can be selected for desired genetic traits. A newly isolated strain can develop the ability to grow to higher titer in embryonated eggs by acquiring this trait from the AOPR8(HON1) strain, and can be selected by the terminal dilution technique and by treatment with anti-HON1 antisera. In addition to acquiring the ability to grow to high titer, surface antigens  may also be transferred, and the progeny can be selected by immunologic methods. It appeared likely that other genes, including those coding for virulence or attenuation might also be exchanged during the recombination procedure. We explored this  question by infecting mice with recent strains of H3N2 influenza virus, and with some of their progeny which had been selected for high virus yields from eggs, after recombination with the AOPR8(HON1) virus, a strain known to be virulent for mice. Influenza (H3N2) virus strains A/Scotland, A/Port Chalmers and A/England which  were isolated and passaged in embryonated eggs did not cause death when administered intranasally to three-week-old Swiss mice; however, after recombination with the A/PR8(HON1) virus, these viruses become lethal in mice. This acquisition of virulence appears to be secondary to exchange of genetic information from the parent AOPR8 virus. Virus isolated from  mice infected with these recombinants is antigenically H3N2, the mice develop anti-H3N2 antibodies.


Response of ferrets  to infection with a live attenuated influenza virus and to subsequent heterologous challenge.

Groups of three ferrets were inoculated with a live influenza vaccine ("Alice" strain) and the degree of protection afforded against a challenge inoculation was measured by several parameters. After vaccination, virus excretion was studied and the genetic characteristics of the virus isolates were investigated. After 5-8 weeks, the challenge inoculations were  performed with antigenic drifts of the H3N2 virus: A/Dunedin/4/73  (Port-Chalmers-like), A/England/635/74 and A/Scotland/840/74. The following parameters of infection were evaluated: temperature rises, clinical symptoms, viral excretion, serological responses and increases in the nasal protein contents (Potter et. al(1972). Immunity to influenza in ferrets. I. Response to live and killed virus.  Brit. J. Exp. Path., 53, 153-167.) A very high degree of protection was observed in the immunized animals.


Intranasal versus subcutaneous rubella vaccination in schoolgirls.

In this study a venous blood specimen was drawn and, at the same time, rubella vaccine was given to 1906 schoolgirls mostly in the pre-pubertal age. To assess the pre-vaccination immune status and the effect of the vaccine, a  second  blood sample was taken 6 weeks later and tested for rubella HAI antibody simultaneously with the first one. RA 27/3 rubella vaccine administered by intranasal route to 81 girls produced a 100% seroconversion rate and the same vaccine strain, given by subcutaneous route to 460 girls,  produced a 94.73% seroconversion rate. Among the 1, 365 schoolgirls who received subcutaneous Cendehill vaccine, the seroconversion rate was 86.68%. Side effects were mild and transient and occurred, as headache, most frequently among the girls who received RA 27/3 vaccine by intranasal route.


Dry aerosol vaccination against Newcastle disease. I. Safety and activity controls on chickens.

A new technic or immunization against Newcastle disease in chicken was developed: this method  consists of dispersing lyophilized products by aerosols. One to fourteen day old chickens, with and without parental antibodies, were vaccinated with increasing amounts (10(-1) to 10(5)EID50) of HB1 and LaSota attenuated viruses. 10(4)EID50, inhaled theoretical dose, gave better results when the animals were challenged with the virulent strain. Under laboratory conditions, no respiratory problems  occurred in vaccinated animals; but there is 10 to 20% mortality among animals treated by aerosols in poultry houses, because of respiratory diseases developed after vaccination.


Research and development of unconventional systems for immunization.

The problems raised by the ever expanding world population justify the work of USAID (U.S. Agency for International Development). Continual efforts must be made to develop and efficiently operate methods of control of the microbial and parasitic infections which menace our sources of protein. This programme includes immunization, technical methods in bacterial and viral genetics to obtain attenuated strains, and improvements in production, preservation and distribution of preparations. An example of  an unconventional but promising system of application is the pilot study recently begun in the Missouri-Mississippi River region.


Dry aerosol vaccination against Newcastle disease: II. Serological response in chicks.

Day-old chickens with Newcastle disease maternal antibodies are separated in two batches. One batch (S) is vaccinated by liquid spray method with HB1 strain: the other one (NS) is not vaccinated. At 2, 3 or 4 weeks subgroups from S and NS batches are vaccinated with HB1 strain by dry aerosol method. Serological controls reveal an important increase of Newcastle antibodies within two weeks after dry aerosol vaccination. Then a drop of the antibody quantities is observed during weeks 2 to 4 post dry aerosol vaccination. In the following weeks, the antibody level increases very slowly.


Aerosol administration of Newcastle disease vaccines at one day of age.

Newcastle disease vaccines were administered at one day of age by 3 general procedures: 1) discharge of a vaccine aerosol over chicks confined in an enclosed space, 2) aerosol adminstration in a poultry house, 3) a commercial device which emits a fine spray into the nasopharynx while the chick is being debeaked. From this work the following conclusions have been drawn: 1) All 3 methods are of some value with respect to the development of antibody titers and resistance to challenge. 2) The efficacy is universely proportional to the maternal antibody titer. 3) Aerosol vaccination into an enclosed air space is superior to the other methods tested. 4) Day-old vaccination is useful primarily in conferring some early resistance until a subsequent aerosol vaccination at 9-14 days of age confers additional protection. Other important factors include strain of vaccine, vaccine titer, the nature of the diluent, and site of the aerolized particles.


Studies on vaccination against Newcastle disease with the "Komarov" strain of virus by the drinking water.

After a brief reference to the ordinary use of the "Komarov" mesogenic vaccinal strain of Newcastle disease virus for the secondary  vaccination of domestic fowls, the authors deal with laboratory experiments conducted to ascertain that this strain can be used for the same purpose by the drinking  water method. Three groups of chickens 45 days old previously vaccinated with LaSota strain in the drinking water at 20 days old, were revaccinated with the normal dose by the "Komarov" strain, as follows: a) intramuscularly, b) by the drinking water and c) per os. A fourth group was left as negative control. To investigate the effect of the revaccination by the two different routes of administration, the hemagglutination-inhibition test was used. The results of these tests are finally compared and discussed.


Antibodies in blood and secretions of chickens immunized parenterally and locally with killed Newcastle disease virus vaccine.

In mammals the antibody activity in secretions is associated with the secretory IgA. This unique immunoglobulin plays a major role in immunity against infectious diseases of the alimentary and the respiratory tracts. We found a similar system of local immunity against Newcastle disease virus (NDV) in the fowl. Airway washings and bile globulins of chickens were examined by immunodiffusion and immunoelectrophoretic methods. No antigenic differences were found between the serum IgA  and the secretory IgA of airway washings and of bile. The chicken IgA differs from mammalian IgA by lacking secretory component. Antibodies in the airway washings and in tears of chickens immunized by aerosol ir i.m. NDV vaccine (attenuated or inactive) were compared to serum antibodies produced by similar methods of administration. HI antibodies in secretions reached higher levels after aerosol vaccination than after i.m. administration, whereas in serum the situation was reversed. The antibody activity in airway washings and in tears is associated with IgA, while in serum the main antibody is IgG.


An interim report on the work of the Avian Products Standardization Committee.

This Committee was established during the course of the IABS International Symposium on Requirements for Poultry Virus Vaccines held in conjunction with the Foundation Mérieux at Lyon, France, from 28-30 August, 1973. The sub-committees appointed by this Committee have now submitted resports of their individual activities and it is the purpose of this communication to present in summary form the work which they have so far accomplished.


The oral rabies immunization of foxes and dogs with sausage baits.

Foxes wer immunized orally with an attenuated rabies vaccine, ERA, grown on BHK cells. The liquid vaccine was placed in plastic straws, which in turn were incorporated into smoked sausage baits, acceptable to and readily ingested by the animals. When the baits were bitten and the meat swallowed, an oral immunizing dose of vaccine resulted in circulating antibody titers in foxes (and dogs); the animals with antibody resisted a "street" rabies virus challenge that killed unvaccinated controls. The immunization was strictly lingual and buccal, and foxes with interrupted esophagi developed antibody only if the vaccine was deposited in the mouth, while those given a similar dose in the ventral esophagostomy opening (below the interruption and close to the stomach) failed to develop antibody. A casein hydrolysate derivative resulted in such stabilization of the liquid that even when baits were held at 35 degree C for 3 days, similar to extreme field conditions, an immunizing titer for foxes (greater than or equal to 10(4.5)LD50) was still maintained.


Experiments with a model of aerosol immunization of mice and swine against Erysipelothrix insidiosa (E. i.).

Whole antigens  as well as antigen fractions from E.i. were tested as aerosol vaccines. The aerosol produced by a jet nebulizer (Pari, Standard 088) with a capacity of 15 1 air per min and about 10g vaccine per hour was tested by size measuring of the aerosol particles and bacteriological evidence of E.i. in lung tissue. The main concern of the studies was to test the immunogenicity for laboratory animals which were exposed to the vaccines in a modified Henderson apparatus or in boxes of 30 1 respectively. Vaccination trials with conventional mice and piglets did not produce 100% protection against challenge infection by aerosol or subcutaneous route. Experiments with gnotobiotic piglets resulted in sufficient immunity against aerosol challenge with 100 LD50  when aerosols with living avirulent bacteria (strain B 10) were applied three times for one hour or once during three hours. A commercial vaccine from lyzed bacteria immunized only when aerosols were applied three times for three hours. For further immunological evaluation the sera of piglets were tested by means of an indirect fluorescent technique and by other serological methods.


Oral immunization against tetanus.

Model experiments in mice were used for the investigation of oral immunization against tetanus. The efficacy of oral tetanus toxoid application was tested by subcutaneous challenge (10 LD50 tetanus toxin) and antitoxin determination by L+-method. Reasonable protection could only be achieved when toxoid was in intensive contact with the mucous membranes of the oral cavity, whereas immunization by way of the gastrointestinal tract failed completely. After a single oral vaccination with 200 Lf fluid tetanus toxoid onto mucous membranes of the oral  cavity the efficiency index was 75.  A 100% protection was obtained in challenge after 3 applications of 200 Lf toxoid. In comparison, a single subcutaneous dose of 2 Lf tetanus toxoid resulted in an efficiency index of 100 and a  single intranasal immunization with 100 Lf in an efficiency index of 93. Development of immunity after oral immunization was much accelerated if compared with parenteral immunization. 20% of the orally treated animals were immune  5 days after vaccination. After the same period subcutaneously treated animals had failed to develop any protection at all. Antitoxin titers after one oral vaccination (200 Lf) were similar to the ones after one subcutaneous dose (2 Lf). A distinct increase in antitoxin titers could only be observed when revaccination was done subcutaneously. The results obtained with mice apply analogically to guinea pigs.


Active avoidance and brain DNA after postnatal food deprivation in rats.

Fond deprivation was produced in infant rats, from 2 to 20 days of age, by a procedure designed to minimize reduction in maternal care. Body weights in the deprived animals were 60% of control weights at 7 days, 65% at 20 days, and, after ad lib feeding, 89% at 4 months. No change was observed in the rate of acquistion of a conditioned active avoidance response in the food-deprived rats when compared with their littermate controls when tested as adults. No lasting reduction in cerebral desoxynucleic acid (DNA) was observed despote a 9% reduction in cerebellar DNA.


Depth perception after infant and adult visual neocortical lesions in light- and dark-reared rats.

In 2 experiments the behavior of light- and dark-reared infant- and adult-operated striate rats were compared at 20-160 days of age on a visual cliff apparatus in which the depth of the deep side could be varied. Differential depth thresholds revealed that depth discriminative ability did not develop normally following removal of the striate cortex in infancy. Further, infant-operates who were reared in darkness following their operations performed less well than their light-reared, infant-operated counterparts. The infant-operated animals, regardless of their postoperative rearing condition, performed significantly better than did adult-operated animals after comparable post-operative recovery periods and testing. The results are discussed in terms of further specification of the role played by age of operation and by the interaction between visual experience and age of operation.


Effects of differential cue availability in an active avoidance CS for young and adult rats.

In Experiment I, groups of 22-and 140+-day rats were trained in acquisition and extinction of 1-way avoidance with a CS that consisted of the opening of a guilotine door 5 sec before US onset or a combination of door-opening plus a tonal signal that remained on until the occurrence of the motor response. Under both CS conditions, avoidance acquistion was similar at each age level. The extinction date indicated comparable performance for the young subjects but differential performance and greater resistance to extinction for the adult subjects. Adults trained with the door-opening CS persisted in responding for an entire series of 100 extinction trials, whereas the adults trained with the compound CS extinguished well within the 100-trial, whereas the adults trained with the compound CS extinguished well within the 100-trial limit. A 2nd experiment included 10 pre-exposures of the simple or compound CS's prior to avoidance training. Although the pups were insensitive to pre-exposure effects, the adults that were pre-exposed and trained with identical CS's showed evidence of pre-exposure effects. Results of both experiments were interpreted as indicative of differential cue saliency between ages.


Scopolamine's effect on passive avoidance behavior in immature rats.

Male albion rats ranging in age from 15-30 days were injected with either scopolamine hydorbromide or saline, prior to training and retention testing on a black-white passive avoidance (PA) task. Pretraining administration of a 1.0-mg/kg dose of scopolamine significantly increased the median number of trails to criterion for 18-, 21-, and 30-day-old rat pups when compared with their saline controls. Fifteen-day-olds showed drug-related PA deficits when a 2.0-mg/kg dose was given. Retention data reflect characteristic age-dependent memory loss over the 1-week acquistionretention period with no apparent state-dependent effects. The data suggest the presence of cholinergic inhibitory mediation of PA responding in preweanling and postweanling pups.


The influence of early auditory experience on later auditory and tactual variation seeking in the rat.

Albino rats were raised under 1 of 4 conditions of auditory stimulation from 22-35 days of age. At 40 days, preferences for auditory and tactual variation were assessed in separate runway tests. Results were analyzed in a split-plot design for each of 2 measures of variation seeking. Subjects experiencing more-variable early stimulation scored higher than subjects receiving less-variable stimulation on 1 measure of variation-seeking and lower on the 2nd measure. The effect was intermodal since these results were obtained for tactual as well as auditory variation seeking.


A comparison of live and videorecord viewing of infant behavior under sound stimulation. III. Six-month-old babies.

Ten clinically normal 6-month-old infants were presented with a series of sound stimuli while their behavior was simultaneously videotaperecorded and assessed live by 2 sound-masked observers. Two weeks later the same observers assessed the behavior from the videorecords. In both situations observers were permitted to see the babies for 13 sec at each trial. The first 5 sec formed a prestimulus observation period and the following 8 sec possibly contained a sound stimulus. Between trials the observers were allowed 20 sec in which to not (1) prestimulus activity, (2) confidence in response, and (3) facial, digit, and limb movements and "wholistic"impressions (e.g., "stilling"). The agreement between the live and video situations was modest for prestimulus activity and confidence in response, and fair to good for movement item. The outcome was rather similar to that of our earlier work on neonates and 6-week infants, although it did suggest a small loss of information with the videorecording of 6-month infants.


The stability and interrelationships of newborn sucking and heart rate.

The sucking behavior of 44 newborns was recorded along with heart rate (HR) and respiration. These 3 systems showed stability over a 24-hr period. Sucking parameters varied markedly depending upon whether the infant was sucking for sucrose or under a no-fluid condition. Moreover, HR was strikingly affected by sweetness. The direction of HR change was toward increasing rates when sucking for sweet, even though sucking for sweet substances occurs more slowly than for no fluid.


Position reversal deficit in young ferrets.

Young ferrets (6 and 10 weeks old at the start of the experiments) were compared to adult ferrets on learning (1) a Lashley III maze, (2) a left-right discrimination in T-maze with identical choice arms, and (3) a reversal of the left-right discrimination. The young were not inferior to the adults in learning either the Lashley III maze or the initial discrimination in the T-maze. However, the young were markedly (and significantly) inferior to the adults in learning to reverse.


Behavioral development in three hamster species.

The preweaning behavioral development was compared in 3 hamster species: the golden (Mesocricetus auratus), Chinese (Cricetulus griseus), and Djungarian (Phodopus sungorus). Differences in the age of appearance of action patterns could not be summarized by simply ranking species on either precocity or developmental speed, nor were they eliminated by measuring age from conception. Problems in the interpretation of species differences in the age of appearance of action patterns are discussed.


The effect of reinstatement stimulus conditions on the maintenance of long-term memory.

Weanling rats trained on an appetitive SDSdelta discrimination were subsequently exposed to different components of the training stimulus for 15 min each week for 10 successive weeks. On the week following the final stimulus exposure retention was measured by a 2-hr relearning test. Those subjects exposed to all acquisition cues (SDSdelta with reinforcement), as well as those exposed to Sdelta conditions alone, demonstrated enhanced retention relative to a control group receiving no reinstatement experience. All other exposure conditions including presentation of SD with reinforecement were either ineffective or impaired retention.


Motor reactions during the antenatal period correlated with the periodic change in the activity of the cardiovascular system.

A connection between the periodic appearance of vagal bradycardia and of intrauterine large-amplitude respiratory movements, as well as the appearance of generalized jerky-type and more sustained extensor motor reactions, has been established in experiments on dog fetuses connected with the mother through the umbilical cord. Brief vagal bradycardia also arises immediately after completion of these reactions and is an analogue of the vagal phase in adults after motor activity. These correlated phenomena are caused by periodic reversible mild hypoxemia which through the chemoreceptors of the sinocarotid zone stimulates the centers of vagal innervation of the heart and the centers of innervation of skeletal muscles. These phenomena disappear when the mother inhales a gas mixture containing less than 14-15% oxygen or greater than 50-60% oxygen, as well as when the mother is under deep anesthesia.


Stability of motor OR and heart rate habituation rates of infancy.

The stability of the OR habituation rate as an individual difference trait was investigated in 2 studies. The 1st focused on motor OR's to auditory stimuli at 3 ages within the 1st month of life, and the 2nd examined the HR responses to auditory stimuli at 4 and 8 months. The results indicate that motor OR's did not differ significantly with age and were moderately stable across ages. The stability decreased with age across consecutive days but increased across consecutive weeks. The cross-age correlation for HR responses was moderate. The results were compared with similar findings on other parameters of the OR.


Effects of pre- and postnatal litter size reduction on development and behavior of rat offspring.

Litter size was reduced to 2-5 rat pups either prenatally by unilateral maternal oviduct ligation (Group PRN) or postnatally by removing pups (Group PST). Normal size litters (8-10 pups) of sham ligated (SHM) and intact (CON) mothers served as controls. Weights at 30 days were increased by prenatal or postnatal reduction and reduced by prenatal stress (SHM); the sex difference in weight was most pronounced in PRN rats. At 75 days PRN rats were heaviest, with no differences between the other groups. Relative ovarian weights were reduced in PRN females and absolute testes weights increased in PST males. The PRN and SHM females had smaller relative adrenal weights than CON and PST females. Open-field activity was generally increased by prior avoidance conditioning and effects of treatments were found only in groups tested after avoidance-conditioning: PRN and SHM rats were more active than PST and CON rats, particularly on Days 1 (SHM) and 4 (SHM and PRN) of testing. Passive-avoidance behavior of PRN rats was also more susceptible to previous test experience: they emerged more slowly if they had prior open-field experience. The PST animals, in contrast, emerged more rapidly after prior test experience. Plasma corticosterone levels and shuttlebox conditioning and extinction were unaffected by treatments.


Escape learning in infant mice as a function of drive level and drive shifts during acquisition.

Separate groups of 9-day-old Swiss-Webster mice began straight-alley escape training at .1 or .4 mA. After 12 trials, half of the mice in each group were shifted to .4 or .1 mA, respectively, whereas the remaining half continued at their original level for an additional 12 trials. Twenty-four hours later, half of each of the 4 shock-level groups were retested at .1 mA, half at .4 mA. The results indicated that those groups which made a large number of competing responses during early trials and showed a gradual reduction over training trials (.1-.1 and .1-.4) emitted the fewest number during retest at either shock level. In contrast, those groups with either limited (.4-.1) or no (.4-.4) opportunity to decrease competing responses during training showed evidence of poor (.4-.1) and no (.4-.4) retention of learned inhibition of that response. Running speed was clearly a performance measure, as it only reflected existing shock levels during both training and retention trials.


Carbohydrate metabolism and capillary basement-membrane thickness in children. I. cross-sectional studies.

Thirty-nine children from three to 16 years of age were included in this study. Nineteen were diabetics, seven were "suspected" diabetics (with evidence of glucose intolerance but without repeated fasting hyperglycemia), and 13 were controls. Mean glucose disappearance rates (K) during intravenous glucose tolerance tests (IVGTTs) were 2.19 for the controls, 1.23 for the suspected diabetics, and 0.70 for 14 diabetics tested; the differences were statistically significant. Diabetics had the smallest and suspected diabetics the greatest plasma insulin responses during IVGTTs. Fasting plasma growth hormone (GH) varied widely. GH generally decreased or remained unchanged during IVGTTs, but two diabetics exhibited slight increases and two sustpected diabetics pronounced increases. Basement-membrane thickness (BMT) was examined in 42 quadriceps femoris needle biopsies. Average BMT (ABMT) and minimum BMT (MBMT) correlated well (r = 0.91). BMT did not correlate well with age or, in the diabetics, with duration of clinical disease. Diabetics had the greatest and controls the least mean ABMT and MBMT, but the differences were not statistically significant. High values (those exceeding mean control values by more than two standard deviations) were much more common among the suspected diabetics and the diabetics. One of 13 controls, three of six suspected diabetics, and six of 19 diabetics had high ABMT values; two suspected diabetics and five diabetics had high MBMT values. Correlations between BMT and K were negative for the most part, but correlation coefficients were small. Serial studies in four of the children suggest that BMT and glucose tolerance tend to change in opposite directions.


Carbohydrate metabolism and capillary basement-membrane thickness in children. II. Longitudinal studies.

Longitudinal biochemical and histologic studies were carried out in 11 children receiving oral hypoglycemic agents. There were five "suspected" diabetics (with evidence of glucose intolerance but without repeated fasting hyperglycemia) and six diabetics. Mean fasting plasma glucose (FPG) values showed no significant change during treatment with phenformin alone. The mean FPG decreased significantly within six to 10 weeks after addition of tolazamide to the regimen, but the decrease was not sustained during long-term observation (seven months to four years). Glucose disappearance rate (K) generally increased as FPG decreased, but the number of observations was smaller, and mean values showed no significant change. Mean values for fasting plasma insulin and for peak insulin response to intravenously administered glucose did not change significantly. Changes in capillary basement membrane thickness (BMT) were found to be statistically significant in a number of individual instances. Decreasing BMTs were associated with increasing Ks and vice versa. A similar trend was apparent among other patients, in whom individual changes in BMT were not statistically significant. The pooled data were therefore subjected to chi-square analysis; K and average BMT were found to change in opposite directions (P less than 0.001); a similar relationship held for K and minimum BMT (P less than 0.05). But K and BMT did not correlate well as regards magnitude of change. Influences of phenformin and tolazamide on these changes could not be evaluated. Both BMT and K may be influenced by many complex variables, but the present findings indicate that glucose tolerance and BMT have a close interdependence.


Locating the site(s) of insulin resistance in patients with nonketotic diabetes mellitus.

Insulin resistance and the ability of insulin to inhibit hepatic glucose production and to increas efficiency of glucose uptake were determined in 24 nonobese individuals: eight subjects with normal oral glucose tolerance, eight patients with chemical diabetes, and eight nonketotic patients with fasting hyperglycemia (greater than 150 mg. per cent). Insulin resistance was estimated by measuring the steady-state plasma glucose response to a continuous infusion of insulin, glucose, epinephrine, and propranolol. This approach permits us to inhibit levels of exogenous insulin, and use the height of the steady-state plasma glucose response as a direct estimate of insulin resistance. The ability of insulin to inhibit hepatic glucose production and to increase efficiency of glucose uptake was calculated from the results of two studies in which a continuous infusion of 3H-2-glucose was used to measure glucose turnover rate. The first study was performed after an overnight fast, under conditions of basal insulin levels, while the second was conducted during the infusion of insulin, glucose, epinephrine, and propranolol. Hepatic glucose production is equal to glucose turnover rate during the basal study and is equal to glucose turnover rate minus the infusion rate of cold glucose during the second study. Glucose uptake in both studies is equal to glucose turnover rate minus urinary glucose loss, and the efficiency of glucose uptake is calculated by dividing glucose uptake by the plasma glucose pool size. The mean (+/- S.E.) steady-state plasma glucose response was 113 +/- 9 mg. per cent in normal subjects, 205 +/- 14 mg. per cent in chemical diabetics, and 346 +/- 30 mg. per cent in patients with fasting hyperglycemia. Thus, insulin resistance exists in monoketotic diabetes, and the greater the degree of glucose intolerance, the greater the insulin resistance. The resistance to the insulin infusion in patients with chemical diabetes seemed to be mainly a function of the inability of insulin to increase efficiency of glucose uptake, since insulin did retain its ability to inhibit glucose production (although not to normal levels). In contrast, the infusion of insulin neither inhibited hepatic glucose production nor increased efficienty of glucose uptake in patients with fasting hyperglycemia. Thus, the insulin resistance that exists in patients with nonketotic diabetes cannot be considered to be a global phenomenon. Significant differences exist in the responsiveness of various tissues to the two general aspects of insulin's action on glucose homeostasis, and these differences provide a physiologic basis for the variations in degree of over-all insulin resistance that are present in the three groups of subjects.


Nodular intercapillary glomeruloscerosis in diabetes secondary to chronic calcific pancreatitis.

Nodular (specific) intercapillary glomerulosclerosis (Kimmelstiel-Wilson) was found at autopsy in a 47-year-old man who had been diabetic for 20 years. The family history for this disease had been negative. Both the clinical course and the autopsy findings strongly suggest that this patient's diabetes was secondary to chronic fibrocalcific pancreatitis. This is only the fourth recorded case of histologically documented nodular glomerulosclerosis occurring in a patient with pancreatogenic diabetes.


Is cigarette smoking more frequent among insulin-treated diabetics?

During epidemiologic investigations of vascular complications of diabetes in Warsaw the habit of cigarette smoking was analyzed in the subjects studied (4,530 diabetics). It was found that in the group of diabetics the number of ex-smokers was much greater (p less than 0.01) and that of present smokers lower (p less tan 0.01) than in a representative sample of the Warsaw population. Furthermore, it was observed that in the subgroup of insulin-treated diabetics the number of smokers was highest and the number of ex-smokers and nonsmokers was lowest in relations to other treatment subgroups.


Plasma glucose and insulin responses to orally administered simple and complex carbohydrates.

We have studied the effects of glucose, sucrose, and various starches on postprandial plasma glucose and insulin responses in 19 subjects. All carbohydrate loads were calculated to contain 50 gm. of glucose, and the response to each carbohydrate was tested twice: when given alone in a drink or when given in combination with other nutrients as a meal. The data demonstrate: (1) Glucose and sucrose elicited similar plasma glucose response curves, but sucrose elicited a somewhat greater (20 per cent) plasma insulin response. (2) Raw starch ingestion resulted in a 44 per cent lower glucose response and a 35-65 per cent lower insulin response than did either glucose or sucrose ingestion. (3) When carbohydrate was given as a meal the plasma glucose responses were 40-60 per cent lower than when the same carbohydrate was given as a drink, while the insulin responses were generally similar, and (4) when different cooked starches were compared, the plasma glucose and insulin responses to rice were significantly lower (50 per cent) than to potato. In conclusion, the size of the carbohydrate molecule appears to influence the postprandial glucose and insulin responses such that more complex carbohydrates (starches) elicit lower responses. This effect may be related to differences in digestion rather than to differences in absorption.


Total cardiac denervation in diabetic autonomic neuropathy.

Total loss of the autonomic regulation of heart rate is described in a 28-year-old diabetic with extensive autonomic neuropathy. The patient had an almost fixed heart rate that barely responded to any of the tests that stimulate or inhibit the autonomic nerves. Its behavior was similar to that of the transplanted heart.


Effect of ethanol on the glucose-mediated insulin release in triply catheterized anesthetized pigs.

In order to further elucidate the potentiating effect of ethanol on the glucose-mediated insulin response, triply catheterized anesthetized pigs were submitted to an intravenous glucose infusion test after a four-hour preinfusion with ethanol (11 pigs) or saline (six pigs, control experiment). During the tests portal, hepatic, and peripheral venous blood was drawn simultaneously. Two series of ethanol-preinfusion experiments were carried out: in one series the serum ethanol concentration was maintained at approximately 10 mM and in the other at 19 mM. Compared with saline, 10 mM of serum ethanol induced a more than threefold increment in the insulin secretory response to glucose as estimated in the portal blood (p less than 0.01). Likewise, hepatic and peripheral venous blood insulin levels were enhanced (p less than 0.01). In contrast, 19 mM of serum ethanol did not elevate serum insulin levels above those found in the control experiments. When individual incremental portal insulin areas were plotted against the corresponding average value of serum ethanol in the preinfusion period, a significant inverse relationship was found (p less than 0.02), indicating a decrease in the potentiating effect of ethanol on the glucose-mediated insulin response with increasing levels of serum ethanol. Comparison of portal and hepatic incremental insulin areas revealed that ethanol did not, in the concentration range investigated, influence the hepatic insulin degradation rate. In conclusion, ethanol seems to potentiate, in an inverse concentration-dependent manner, the glucose-mediated insulin response through an action directly on the pancreas.


Insulin and brain metabolism. Absence of direct action of insulin on K+ and Na+ transport in mouse brain.

This is a study of the effect of insulin on the transport of K+ and Na+ from the blood into the brains of normal mice. Despite profound reductions in plasma and brain glucose levels, reduction of plasma K+ concentration and progressive deterioration of neurologic function 30-120 minutes after insulin injection, in 20-22-day-old animals there was no increase in brain K+ and Na+ concentrations. In fact, at 120 minutes, when the brain water content increased 0.7 per cent, brain K+ concentration was significantly reduced, not elevated. The effect of insulin on brain electrolyte and water content in adult mice was also studied. Although brain water increased 0.5 per cent at 120 minutes, there was no changes in brain Na+ or K+ concentrations at any time after insulin injection. The data from mice do not support a role of insulin in electrolyte transport in brain.


Effect of diabetes mellitus and insulin on the turnover and metabolic response to ketones in man.

To determine the effect of diabetes mellitus on ketone removal rates, Na DL-beta-hydroxybutyrate was administered as a continuous three-hour infusion (3 mg./kg./min.) to healthy volunteers and insulin-dependent diabetics in the postabsorptive state. An additional group of healthy controls received intravenous glucose (50 gm.) or glucose and insulin during the ketone infusion to determine the effect of hyperinsulinemia on ketone removal. Following ketone infusion, total blood ketone levels in the diabetics were twofold greater than in controls (p less than 0.001). The metabolic clearance rate of ketones (MCRk) in the diabetics was reduced by 42% from that of controls (p less than 0.001). In contrast, the calculated production rate of ketones (PRk) in diabetics was not consistently different from that observed in controls. In diabetics with normal PRk, MCRk remained significantly below control values (p less than 0.001). The ketone infusion resulted in a fall in plasma glucose and alanine levels in the normals as well as diabetics. However, the decline in plasma glucose induced by the ketone infusion was five- to sixfold greater in the diabetics than in controls (p less than 0.005) and correlated linearly with the decline in plasma alanine (p less than 0.02). Administration of intravenous glucose during an ongoing ketone infusion in normal subjects resulted in 37 +/- 5% reduction in beta-hydroxybutyrate, but no change in acetoacetate concentration. The decline in beta-hydroxybutyrate was two- to threefold greater than would be expected if glucose had acted solely to inhibit endogenous ketone production. Similar results were observed when hyperinsulinemia without hyperglycemia was produced by simultaneous administration of insulin and glucose. It is concluded that (1) ketone disposal is reduced in diabetes even when ketone production is normal, suggesting the rate of ketone utilization may be a more sensitive index of insulin deficiency than is ketone production; (2) hyperinsulinemia stimulates beta-hydroxybutyrate utilization without influencing acetoacetate concentration; and (3) increased blood ketone levels induced by infusion of Na DL-beta-hydroxybutyrate reduce plasma glucose and alanine concentrations in diabetes. These findings thus support a role for insulin in influencing ketone disposal in normal as well as diabetic man and a role for ketones in influencing substrate availability for gluconeogenesis in diabetes.


Birth order, family size and school failure.

The effect of birth order on educational outcome in the Netherlands is reported for two major social classes, manual and non-manual. The rates of school failure (those who attended schools for the mentally retarded and who failed lower school) were studied in a population of some 200,000 young adult Dutch males born between 1944 and 1946 and whose families of origin had from one to six children. The data used were the records of the Dutch military pre-induction examination. Rates of school failure rose both with increased birth order and with increased family-size, with the exception of one-child families. School failure rates for the first, middle-and last-born were examined for the two social classes, with family size controlled. In general, school-failure rates were significantly related to birth-order position. For each family size and in both social classes, the last-born were at greater risk of school failure than were the first-born.


The prevalence of language delay in a population of three-year-old children and its association with general retardation.

Using a simple assessment of language and a behaviour screening questionnaire, a one-in-four random sample of a total population of three-year-olds was screened for the presence of language delay and behaviour problems. A full psycho-developmental assessment was carried out in children with suspected language delay or a behaviour problem, and in a group of control children, and the sensitivity and specificity of the language screening-test was examined. The results showed the importance of investigating language delay in relation to nonverbal abilities. Of those children with a language age less than two-thirds of their chronological age, 37 per cent also had similarly delayed non-verbal mental abilities. 50 per cent of the children with a language age of less than 30 months were generally retarded in their non-verbal abilities. The estimated prevalence of delayed language development is 31 per 1000, of specific language delay 5-7per 1000, and of severe retardation 4-2 per 1000. Boys were most likely than girls to have language and general developmental delay.


Tactile-perceptual functioning in relation to intellectual, cognitive and reading skills in younger and older normal children.

Forty-eight 12- to 14-years-olds and 40 six- to eight-year-old normal boys and girls were distributed into two groups on the basis of the number of errors they made on several tests of tactile-perceptual ability. The groups were then compared on measures of intellectual, cognitive and reading ability. In the older group, children with poor tactile-perceptual skills performed significantly less well on the other measures than children with few tactile-perceptual errors. This relationship was not so clearly demonstrated in the younger groups. The results are discussed in terms of individual differences in brain function.


Early hospital admissions and later disturbances of behaviour: an attempted replication of Douglas' findings.

This study confirms the findings of Douglas (1975) that single hospital admissions of children for up to a week carry no increased risk of later emotional or behavioural disturbance. The study also confirms Douglas' finding that repeated hospital admissions are significantly associated with disturbance in later childhood. The association probably applies to both emotional and conduct disorders, is most marked in the case of children from disadvantaged homes, and it may well reflect a causal influence. The validity of the finding is strengthened by the fact that detailed psychiatric assessments gave rise to much the same findings as did teacher questionnaire scores. However, in both cases, repeated hospital admissions are associated with only a small minority of disorers and account for little of the variance in children's behaviour.


Obstetric history and the heart-rate response of newborns to sound.

Two groups of clinically normal newborns, differing in the number of non-optimal factors in their obstetric history, were compared by measuring heart-rate response to a series of auditory stimuli. There was a significant difference between the groups in the direction of the average heart-rate response. The high risk" group showed more heart-rate acceleration and less deceleration compared with the "low-risk" group. The heart-rate responses were significantly related to the number of non-optimal obstetric conditions and to parity, but not to the maternal pre-delivery medication score. The greater the "risk" at birth, the less was the deceleration; the greater the maternal parity, the less did acceleration occur in response to auditory stimulation. There was no significant difference between the high-risk and low-rsik groups in heart-rate response trends over trials. Both groups showed reliable diminution of deceleration heart-rate response over trials.


Prognosis of infants of diabetic mothers in relation to neonatal hypoglycaemia.

A prospective follow-up study was conducted to determine whether neonatal hypoglycaemia in infants of diabetic mothers affects subsequent neurological and intellectual performance. 37 such infants (25 hypoglycaemic and 12 non-hypoglycaemic) were examined for physical, neurological and developmental performance at an average age of 4 1/2 years. 11 children were abnormal, with generalised retardation and neurological abnormalities, or delays in particular areas of development; three children were possibly abnormal; and 23 children were normal. Abnormality at follow-up could not be related to neonatal blood glucose level, to the duration of hypoglycaemia or to any other measurement made in the neonatal period, nor to any factor relating to the maternal diabetes. Compared with the normal children, the abnormal group had slightly small head-circumferences at birth relative to their gestational age, but a follow-up there was no difference in head size. At follow-up the children of diabetic mothers tended to be shorter than average. The poor prognosis of the infants in this study was not due to brain damage caused by neonatal hypoglycaemia.


Central nervous system damage as a possible component of unexpected deaths in infancy.

A longitudinal study of 1553 infants, designed to provide early indicators of gross developmental problems by using a behavioral assessment scale, included 12 infants who later died suddenly and unexpectedly. In a retrospective examination of neonatal records, considerable evidence of central nervous system damage was found. Anoxic conditions and even possible seizure activity were implicated. Abnormalities of muscle tonus, skin color and cry were found, together with some visual problems. These findings on behavioral assessment in the neonatal period appear to identify a population which is at greater risk of sudden death in infancy. The need for oxygen therapy as a high-risk indicator of sudden unexpected death has been reported in a previous study and is further substantiated by the present findings: they are also compatible with thos of Naeye (1973), who found long-term hypoxic conditions in autopsy studies on the sudden infant death syndrome. It is suggested that the possibility of central nervous system involvement in the aetiology of the sudden infant death syndrome should be more thoroughly investigated.


Immunological status in tuberous sclerosis.

Cellular and humoral immunity, and lymphoid organ pathology, have been investigated in 10 institutionalized patients with tuberous sclerosis and 10 institutionalized matched controls without the disease. Type and incidence of infections and tumours were reviewed for each group, as was current medication. Elevated serum IgM levels were found in the patients with tuberous sclerosis, but no immunological deficiency of either cellular of humoral immunity was found, nor was there a difference in infection between the groups. Only patients with tuberous sclerosis had evidence of neoplasia. No morphological or histological abnormalities of lymph nodes, spleen or thymus were present. Explanations for the difference between tuberous sclerosis and ataxia telangiectasia are discussed, together with the effect of immuno-surveillance on the development of malignancy.


Hydrocephalus and congenital clasped thumbs: a case report with electromyographic evaluation.

A one-month-old male infant with hydrocephalus, aqueductal stenosis and congenital clasped thumbs is reported. Electromyographic evaluation supported the hypothesis that the clasped thumbs were a consequence of flexion-extension imbalance, with subsequent muscle contracture secondary to hypoplasia or aplasia of the thumb extensors.


A comparison of the acid and gastrin secretory responses to hypoglycaemia and meals in duodenal ulcer with and without acid hypersecretion to pentagastrin.

In 60 uncomplicated duodenal ulcers (DU), maximum acid output (MAO) and acid output following insulin hypoglycaemia (IAO) were measured, and in 30 patients also the serum gastrin responses to insulin and to standard meals, In 7 normal controls, all 4 items were measured. Thirty-six of the DU had MAO within normal limits (normosecretors) and 24 were hypersecretors. Hypoglycaemic vagal response was higher in all DU than in normals and was, in normo-secreting DU associated with an abnormally large functioning G cell mass. This mass is not increased in hypersecreting DU and the greater vagal capacity is related to a supranormal parietal cell mass. An unknown mechanism, perhaps genetic, directs the trophic effects of an increased vagal drive to the gastrin cell mass in one group of DU and to the parietal cell mass in the other.


Serum and intestinal fluid immunoglobulins and jejunal IgA secretion in Crohn's disease.

Immunoglobulins in serum and proximal intestinal fluids and secretion of IgA by cultured jejunal mucosa were measured in 12 healthy subjects and 36 patients with Crohn's disease. Concentrations of IgA, IgG, IgM, and IgE in serum and intestinal fluids were similar in the two groups, except for increased serum IgA concentrations in the patients. Elevation of IgA and chronicity of disease were correlated, which suggests that the IgA alteration was a response to duration of disease rather than a primary pathogenetic factor. IgA secretion by cultured jejunum was similar in control and patient groups. Thus, no evidence was found that abnormalities of secretory immunoglobulins are pathogenetically involved in Crohn's disease.


LDH isoenzyme pattern of uninvolved gastric mucosa of patients with gastric carcinoma and benign gastric disease.

The LDH isoenzyme pattern of the uninvolved mucosa of gastric cancer patients differs as regards the LDH isoenzyme pattern from that of similar tissue of patients with benign gastric disease; the former tissue is characterised by a high M/H ratio of the LDH isoenzymes (M and H sub-units). A high M/H ratio characterises antral mucosa when the latter is compared with fundic mucosa. Mucosa showing superficial and atrophic gastritis also has a higher M/H ratio, whereas the presence of intestinal metaplasia does not appear to influence the M/H ratio. These observations are consistent with the concept that the tissue from which the cancer arose may possess a pre-malignant biochemical lesion.


The distribution and enteric loss of 51Cr-labelled lymphocytes in normal subjects and in patients with coeliac disease and other disorders of the small intestine.

Peripherally harvested lymphocytes have been labelled with 51Cr, reinjected into human subjects and their distribution then studied. Evidence is presented which suggests faecal loss of 51Cr represents loss of T lymphocytes and that there is normally a pathway of lymphocyte removal into the gut of probable importance in lymphocyte migration streams. In 9 normal subjects, without structural intestinal disease, faecal loss of lymphocytes over 5 days was 0.20% (SEM +/- 0.06) whereas in 5 patients with untreated coeliac disease faecal loss was 1.13 +/- 0.34%, in 7 with Crohn's disease it was 1.01 +/- 0.21% and in 5 with intestinal lymphangiectasia loss was 0.61 +/- 0.10%. In 1 patient with acute tropical sprue, enteric loss was 0.97%. By contrast, faecal loss was normal in 3 coeliac patients in remission on a gluten-free diet. Measurements were also made using an external counter. In contrast to the normals, where count rates steadily diminished, an increasing activity was recorded over the umbilicus over 7 days after dose administration in all the disease categories studied with the exception of the treated coeliacs. The finding of an increased enteric loss of lymphocytes may explain many of the immunological abnormalities in the conditions studied.


Effect of secretin, glucagon and VIP on gallbladder contraction.

The effects on gallbladder contraction of three structurally related peptides, secretin, glucagon and the vasoactive intestinal peptide (VIP) have been compared in urethane-anesthetized guinea pigs. Secretin and glucagon had no effect alone but augmented cholecystokinin (CCK)-induced contractions. VIP decreased CCK-induced contractions.


Effects of acetylsalicylic acid (ASA), ASA plus L-glutamine and L-glutamine on healing of chronic gastric ulcer in the rat.

A chronic gastric ulcer model was produced in rats by the subserosal injection of 20% acetic acid solution (0.015 ml) in order to examine whether (1) acetylsalicylic acid (ASA) irritates the chronic gastric ulcer in active or healed or diminished stage, (2) L-glutamine, given together with ASA, inhibits the adverse effect of ASA. Oral ASA 200 mg/kg/day, given in two divided doses for 10 consecutive days, apparently delayed the healing of the gastric ulcer and irritated the healed ulcer to reulcerate. L-Glutamine, 1,500 mg/kg/day, which was given together with ASA in two divided doses, markedly protected the gastric ulcer both in active and healed stages from the deleterious activity of ASA.


Double wave cohort increase for oesophageal and laryngeal cancer in France in relation to reduced alcohol consumption during the second world war.

Mortality from oesophageal cancer is increasing in France. A cohort analysis indicates that there were two successive waves of increase separated by a non-increase interval for the cohorts born between 1902 and 1916. A similar effect was observed for laryngeal cancer and liver cirrhosis but not for lung and pancreas cancer. This might be related to the reduction of alcohol consumption during the second world war.


The medical treatment of cholesterol gallstones: experience with chenodeoxycholic acid.

Chenodeoxycholic acid has been administered to 50 patients with cholelithiasis and 8 with choledocholithiasis for a period of 15 months at doses varying between 2- and 15 mg/kg/day. Among the 50 patients with cholelithiasis, complete dissolution occurred in 16 and partial dissolution in 15 cases. Among the 8 patients with choledocholithiasis, complete dissolution occurred in 3 and partial dissolution in 2 cases. Lower doses were adopted in an attempt to determine the minimum effective daily dose required to produce gallstone dissolution and to lower the cholesterol saturation index (mean 1.52 +/- 0.73 before and 0.98 +/- 0.36 after treatment). Routine liver function tests were carried out before, during and after treatment; no significant alterations were produced by therapy. Studies of the antipyrine half-life, to estimate hepatic microsomial function were found to be normal (mean 13.61 +/- 2.62 before and 13.21 +/- 3.04 after treatment). In addition, histological investigations of the liver were described. This study confirms the efficacy of chenodeoxycholic acid in the treatment of cholesterol gallstones and gives an indication of the minimum effective dose (7.8 mg/kg/day). At the present doses, it has been shown that there are no substantial modifications in fundamental liver function.


The effect of intravenous theophylline ethylenediamine on serum gastrin concentration in control subjects and patients with duodenal ulcers and Zollinger-Ellison syndrome.

Serum gastrin concentrations were determined after an intravenous infusion of theophylline ethylenediamine (aminophylline) in 10 patients with duodenal ulcer, 9 patients with Zollinger-Ellison syndrome, 7 control subjects and 3 patients with pernicious anemia. Increases of serum gastrin levels were observed in each group. It is concluded that an aminophylline test would not be useful in the differential diagnosis of the Zollinger-Ellison syndrome.


A demonstration that the ratios between human pancreatic enzymes can change in 4 days.

Electrophoretic studies of inactive ductal pancreatic secretions, collected on five successive days following operation, demonstrated up to 18 protein bands. Comparison of the densitometric scans on the first and fourth days was as follows: the patterns from different individuals appeared similar during the periods of slow secretion immediately following surgery, there were obvious changes in the proportions of the slower-moving enzymes between the first and fourth days; the most apparent alteration was in the trypsinogen 2 band which was markedly higher on the fourth as opposed to the first day, and during the 4th-6th days, the patterns for a given individual resembled one another, showing only minor changes among the 8-hour collections.


Effect of heparin on lecithin: cholesterol acyltransferase and lipids in cholestasis.

The effect of heparin on the proportion of cholesterol esters, lecithin/lysolecithin ratio, and lecithin: cholesterol acyltransferase (LCAT) activity was studied in twelve patients with cholestasis. A good correlation was observed between a decreased LCAT activity and the proportion of cholesterol esters, and no consistent variation was noted after heparin. The lecithin/lysolecithin ratio was increased in 7 patients and became normal after heparin in 6 cases. The clearance of lipoprotein-X after heparin seems to be not related to LCAT activity. These results demonstrate that heparin does not modify the LCAT activity, and suggest that heparin induces an increase of phospholipase activity in some patients with cholestasis.


The effects of alterations in villus shape on the intestinal mucosal surface of the albino rat; the relationship between mucosal surface area and the crypts.

The villi and crypts of the small intestine of the albino rat (Rattus norvigicus) have been enumerated and measured at different ages from 2 weeks to 8 months. The number of villi increased up to the third month of age and the number of crypts up to the eighth month.  In the proximal intestine, the mean length of the villus base increased  up to the fifth month as ridge-shaped villi were formed. Villus height was greater proximally than distally and this, and the crypt depth, remained constant from the end of the first month of age. The total villus circumference per unit area of intestine, and the villus circumference per crypt was the same proximally and distally, and was relatively constant after the first month of age. The total circumference of the crypt mouths per square millimeter of intestine was the same proximally and distally and, at all ages, was greater than the total villus circumference. The villus surface area per square millimeter of intestine, or per crypt, remained relatively constant after the first month and was greater proximally than distally, due only to the taller villi proximally. The change from finger-shaped to ridge-shaped villi did not affect the villus mucosal surface area. The changes in villus shape are probably not determined by differences in the rate of crypt cell production.


Combined lactose-D-xylose tolerance test in infancy.

A modified combined oral lactose-D-xylose tolerance test done on ten normal infants showed peak levels of blood glucose and D-xylose levels comparable to the peaks obtained when these tests were done separately in the same subjects. The combined test is recommended to evaluate digestive absorptive function in preference to two separate tolerance tests.


The effect of vasopressin and triglycyl lysine vasopressin (glypressin) on the splanchnic circulation in cirrhotic patients with portal hypertension.

In four cirrhotic patients with portal hypertension we have measured some hemodynamic parameters over 60-120 min; portal venous pressure, hepatic venous pressure, mean arterial blood pressure, hepatic blood flow, transsinusoidal vascular resistance and splanchnic oxygen uptake under treatment with Vasopressin (1 IU/min for 10 min) and glypressin (50 mug/kg body weight). The effect on the parameters was less pronounced with glypressin but of longer duration.


A reassessment of vascular factors in relation to intravascular coagulation.

Sural nerve biopsy was performed in twenty-four diabetic patients, with clinical and electrophysiological evidence of diabetic neuropathy. Material from an autopsy case was also examined. Vessels plugged with fibrin were seen within nerve in nine cases. In three cases fibrin was observed tracking into the vessel wall and in four, older thrombus was observed in vessels. Areas of necrosis in nerve bundles were seen in two of the latter. In two patients there had been a preceding episode of intravascular coagulation. Fibrin deposition within small vessels could well play a part in damaging the diabetic nerve and a disturbance of the balance between deposition and removal by fibrinolysis could explain phasic variation in the symptoms of neuropathy.


Bladder dysfunction and neuropathy in diabetes.

Established urodynamic and electrophysiological techniques have been applied to assess the frequency and extent of autonomic and peripheral neuropathy in 60 subjects with diabetes mellitus; 38 were diabetics with suggestive symptoms and the others were representative newly diagnosed (11) or treated (11) diabetics. Objective evidence neuropathic bladder dysfunction was detected in 43 of them (71.7%). The commonest abnormality was a hypotonic, insensitive large capacity bladder, which condition was usually asymptomatic. Less freuqently (15%) was this complicated by bladder decompensation and sphincter involvement, resulting in excessive residual urine and infection; some of these had bladder paralysis with chronic painless retention of urine (7%). Electrophysiological studies found a sensory defect in the lower limbs in all tested patients (100%), and in 41 patients (69%) as associated motor conduction abnormality, which was more frequent and marked in the lower than the upper limb. These functional abnormalities appeared to be related to the severity of diabetes, but less to its duration. Indeed of 11 newly diagnosed diabetics tested 7 had a peripheral neuropathy and 4 urodynamic abnormalities. The high incidence of bladder dysfunction and peripheral neuropathy in this series indicates the frequency of subclinical diabetic neuropathy and a factor needing more emphasis in diabetic uropathy.


Humoral immunodeficiency to bacterial antigens in patients with juvenile onset diabetes mellitus.

Humoral immunity to bacterial antigens was tested in 49 tissue typed patients with juvenile onset diabetes mellitus (JOD) and in 50 healthy controls. The number of patients with agglutinins to E. coli and staphylococci was significantly lower compared to controls (p less than 0.001, p less than 0.01 respectively). Missing antibody formation to pertussis and diphtheria toxoid could also be detected in a higher percentage of JOD patients than of controls (p less than 0.05; p congruent to 0.05, respectively). By contrast heteroagglutinins to sheep and rabbit erythrocytes were found in similar proportion in both groups and the values of immunoglobulin serum concentrations showed no difference between patients and controls. In addition no correlation between antibody formation and genes of the HLA complex was found. It is suggested that the severely reduced agglutinin formation to bacteria antigens might be partly responsible for susceptibility to bacterial infections in juvenile diabetics.


Gastric inhibitory polypeptide (GIP), gastrin and insulin: response to test meal in coeliac disease and after duodeno-pancreatectomy.

The response of serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG) and insulin (IRI) to a mixed standard meal was measured in 15 controls, 6 patients with coeliac disease, 26 patients with chronic pancreatitis and partial duodenopancreatectomy (Whipple's procedure). Serum levels of IR-GIP, IRG and IRI were significantly reduced in patients with coeliac disease. The serum glucose increase was significantly smaller only during the first hour after the meal. Since small intestinal GIP- and G-cells are situated mainly in the glands of duodenal and jejunal mucosa their absolute number is not significantly reduced in coeliac disease. It is suggested that the release of IR-GIP and duodenal IRG is influenced by the rate of absorption of nutrients. In patients with chronic pancreatitis the IR-GIP release is significantly greater than in controls, the IRG release normal and the IRI response delayed. After Whipple's procedure the IR-GIP response is increased significantly while the IRG secretion is abolished. This demonstrates that the duodenum is not necessary for GIP release and that pancreatic and jejunal gastrin are without clinical significance.


Lower esophageal sphincter and gastric acid response to intravenous infusions of synthetic human gastrin I heptadecapeptide.

Human gastrin I heptadecapeptide was administered by constant intravenous infusion to 7 adult male volunteers without gastrointestinal disease, and serum gastrin concentrations and responses of the lower esophageal sphincter (LES) pressure and gastric acid output were measured and compared. Significant responses in LES pressure were found at gastrin infusion rates which produced submaximal gastric acid output. These LES pressure responses were quantitatively smaller than those occurring concomitantly with similar total immunoreactive gastrin levels evoked by administration of a protein meal in the same subjects. These observations suggest that, although increases in serum gastrin concentrations may contribute to increases in LES pressure seen under physiological conditions after feeding, the increase in LES pressure produced by feeding cannot be explained exclusively on the basis of endogenous gastrin release.


Characterization of a hyperactive segment at the rectosigmoid junction.

During a study of intraluminal motor patterns of the colon and rectum, spontaneous wave activity of a continuous complex type was observed at the rectosigmoid junction in constipated subjects. To assess the frequency and characteristics of this hyperactive segment, 36 subjects with colonic motor disorders and 12 healthy controls were studied. Eighteen of 24 patients with constipation (75%) and 1 of 7 subjects with asymptomatic diverticulosis exhibited a persistent hyperactive segment at the rectosigmoid junction. Neither secretin nor cholecystokinin influenced the wave activity of the hyperactive segment. In contrast, atropine and glucagon inhibited markedly all wave activity and decreased the motility index of this segment significantly, suggesting overactivity of the muscarinic effector cells. It is concluded that a segmental area of overactivity exists at the rectosigmoid junction in most constipated subjects regardless of their underlying disorders.


Amylase isoenzyme clearances in normal subjects and in patients with acute pancreatitis.

Renal clearances of amylase isoenzymes, expressed as percentages of creatinine clearances, were determined in 20 normal subjects and in 8 patients with acute pancreatitis. The isoenzyme assay employed thin layer isoelectric focusing, starch iodine staining, and densitometry. Normal clearance of pancreatic-like amylase (mean +/- SE: 3.00 +/- 0.40%) was greater than the clearance of salivary-like amylase (0.51 +/- 0.06%) in ea ch individual (P less than 0.001). However, the amount of pancreatic amylase in the serum was not the major determinant of amylase clearance. Normal clearance of pancreatic-like amylase was significantly (P less than 0.001) less than the clearance of total serum amylase in acute pancreatitis (6.49 +/- 1.07%). In pancreatitis the clearance of pancreatic-like amylase (7.29 +/- 1.19%) and the clearance of salivary-like amylase (4.55 +/- 1.02%) were both elevated compared to normal (P less than 0.001). These findings indicate that the increased clearance of amylase in pancreatitis results from a change in renal function rather than a change in serum amylase. Renal changes not reflected by increased serum creatinine or more than mild proteinuria may be manifestations of the systemic toxicity of acute pancreatitis.


Serum amylase determinations and amylase to creatinine clearance ratios in patients with chronic renal insufficiency.

Patients with severe chronic renal failure may have significant hyperamylasemia in the absence of clinical symptoms or signs of acute pancreatitis. Amylase to creatinine clearance (CA/CC) ratios were usually elevated in patients with chronic renal failure and were not helpful in evaluating the possibility of acute pancreatitis. The mean amylase to creatinine clearance ratio for the controls with normal renal function was 1.24 +/- 0.13. In patients with chronic renal failure, it was 3.17 +/- 0.42 (P less than 0.001). Serum amylase isoenzyme patterns revealed no difference in salivary to pancreatic isoenzyme ratios between normals (1.04 +/- 0.12) and patients with severe renal insufficiency without evidence of pancreatic disease (1.07 +/- 0.13). The isoenzymes were helpful in excluding the diagnosis of pancreatic in 1 renal failure patient whose hyperamylasemia was primarily salivary in origin and in confirming the diagnosis in another who had only a pancreatic band.


Stimulation of DNA synthesis by big and little gastrin (G-34 and G-17).

Fasted rats were injected six times over a 48-hr period with G-17 I, G-17 II, G-34 II in doses doubling from 3.38 nmoles per kg to 54 nmoles per kg. Twelve rats were studied at each dose. NaCl-injected animals were used as controls. The rats were killed and the in vitro incorporation of [3H]thymidine into DNA as well as the total DNA content of the mucosa of the duodenum and oxyntic gland area of the stomach were determined. All gastrins, as well as pentagastrin, stimulated DNA synthesis. Peak stimulation occurred at 13.5 nmoles per kg for G-17 I and G-17 II and at 6.75 nmoles per kg for G-34 II. Pentagastrin's peak trophic effect was produced by 325 nmoles per kg. In order to compare the efficacies of the various types of gastrins, 60 rats were divided into groups of 12. One group received saline and the other four groups received the maximally effective dose of one of the four types of gastrins. The responses to each of the gastrins were not significantly different, and DNA synthesis was doubled in each tissue. Total DNA content increased slightly, but significantly, in response to each gastrin. Several conclusions can be drawn from these data: (1) G-17 and G-34 possess trophic activity; (2) the efficacies of pentagastrin, G-17 I, G-17 II, and G-34 II for the stimulation of DNA synthesis are not significantly different; (3) sulfation of G-17 has no significant effect on its trophic activity; (4) based on the effects of exogenous molar doses and their respective half-lives, both G-17 and G-34 would be expected to contribute to the trophic effect of endogenous gastrin; and (5) G-17 and G-34 are at least as effective in stimulating DNA synthesis as they are in stimulating gastric acid secretion.


Distribution of excitatory vagal fibers in canine gastric wall to control motility.

The distribution of cholinergic excitatory neurones in the canine gastric wall was studied by recording electrical and mechanical responses to electrical stimulation of the nerves of Latarjet and close intraarterial perfusions of drugs which stimulate nerve and muscle. Electrical stimulation of the anterior nerve of Latarjet produced contractile activity on the anterior side, followed rapidly by activity on the posterior side and vice versa, indicating that the axons of the neurones from each side crossed over to the other. This was not due to the propagation or conduction of electrical response activity, because electrical response activity and contractions induced locally by acetylcholine given into a small artery supplying a segment of stomach did not propagate. The cross-over innervation and the direct innervation were both segmental, in that the response to nerve stimulation dropped out in segments as the branches of the nerves of Latarjet were cut successively. Mainly, preganglionic axons crossed over from the anterior side to the posterior side, but both pre- and postganglionic axons crossed over from the posterior side. This was demonstrated by observing the spread of electrical and mechanical responses, or lack of it, in response to local injections of acetylcholine and dimethylpeprazinium. The study shows that there is a segmental distribution of excitatory neurones in the gastric wall which is appropriate to produce a ring of contraction to control gastric emptying and mixing.


Population kinetics of antral gastrin cells in the mouse.

The proliferation of antral gastrin cells has been studied in adult mice by combining their immunoperoxidase identification on semithin Epon sections with radioautography after single or multiple injections of [3H]thymidine. After a single injection, nuclear uptake of [3H]thymidine was observed in 0.25% of the well-differentiated gastrin cells. Ten days after six successive injections of the precursor, the labeling index reached 4.5%. This indicated that the renewal of the gastrin cell population was very slow. The turnover time was roughly estimated at 2 to 4 months. Analysis of the labeling index curves obtained during and after the administration of [3H]thymidine confirmed that the majority of the gastrin cells were renewed through replication of other gastrin cells. However, differentiation of a fraction of this gastrin cell population from "other" cells in the antrum could not be excluded.


Altered small bowel propulsion associated with parasitism.

Experiments were designed to test the hypothesis that alterations of intestinal motility accompany enteric helminth infections. Motility was measured in rats during the intestinal phase of infection with the nematode Trichinella spiralis by following the transit of radioactive chromium through the gut. Intraduodenal catheters were surgically implanted in rats. One week after the operation one group of animals was infected with 8 x 10(3) T. spiralis larvae and a second group was infected with 16 x10(3) larvae. A third group of uninfected rats served as controls. Three, four, or five days postinfection, Na2 51CrO4 was injected through the catheter into the duodenum or fasted animals and its propulsion through the small bowel was allowed to progress for 15 min. The distribution of radioactivity throughout the small intestine and cecum was then plotted as a function of gut length. Intestinal transit was increased significantly by infection. The leading edge of radioactivity transversed 100% of the gut length in infected rats and 70% in controls. The amount of injected radioactivity transversing the midpoint of the small intestine was estimated by regression equations to be 38% of the injected dose for control rats and 59 and 57% for infected groups. Increased propulsive activity in parasitized rats was associated with inflammatory changes and a significant reduction in disaccharidase levels in the gut mucosa. The latter conditions were most marked in the proximal small bowel where the majority of worms resided.


Hepatitis B surface antigen carrier state in hepatosplenic schistosomiasis.

The prevalence of hepatitis B surface antigen (HBsAg) was studied in 103 cases of hepatosplenic schistosomiasis (HSS), 134 control cases with a variety of illnesses including hepatointestinal schistosomiasis, and 600 blood donors, in an area endemic for both schisfosomiasis and viral hepatitis. The patients with HSS proved to be persistent carriers for HBsAg in a significantly higher proportion than the other two groups of cases. The HSS cases who were carriers of HBsAg had more clinical signs of chronic liver disease and strikingly more chronic inflammation of the portal spaces on liver biopsy. It is suggested that abnormal immunological responses in patients with HSS makes them more susceptible to become carriers of HBsAg and that the addition of this injurious factor makes their basic disease worse, and may be responsible for the development of cirrhosis in some cases.


Necrotizing granulomatous vasculitis (allergic granulomatosis) of the gallbladder.

A case of necrotizing granulomatous vasculitis limited to the gallbladder and manifesting as acute cholecystitis is presented. The different types of vasculitis are discussed and the characteristics of necrotizing granulomatous vasculitis (allergic granulomatosis) are described.


Double duodenal diaphragms in an adult: endoscopic, radiographic, and operative findings.

Hypotonic duodenography, duodenoscopy, and operative exploration were performed in an adult with double duodenal webs and symptoms suggesting gastric outlet obstruction. The spectrum of diagnostic features associated with this rare entity is described in this report.


Ileojejunitis in a pair of identical twins.

A pair of identical twin brothers with identical white and red blood cell antigens and diffuse ileojejunitis is reported. One brother initially presented with granulomatous gastritis, presumably Crohn's disease of the stomach. The relationship of diffuse ileojejunitis to Crohn's disease and the suspected genetic predisposition to develop Crohn's disease are briefly discussed.


Progressive intrahepatic cholestasis of infancy and childhood. A clinicopathological study of patient surviving to the age of 18 years.

A patient who developed chronic cholestatic jaundice during the 1st year of life and eventually died of liver cell failure at the age of 18 years is described. During the terminal illness Kayser-Fleischer-like rings were observed and the serum concentrations of total copper and ceruloplasmin were elevated. At autopsy, a mixed macronodular and micronodular cirrhosis was found and cholangiography and dissection of bile ducts revealed no obstructive lesion of the biliary tract. There was no family history of hepatobiliary disease. Liver biopsies obtained at the ages of 5 and 7 years showed accumulation of bile droplets in hepatocytes, normal-appearing bile ducts, no significant fibrosis, and intact lobular architecture. Striking features of the terminal cirrhosis were the presence of Mallory bodies and a marked excess of copper in the liver (2,175 mug per g dry weight). The latter two findings, as well as the elevated serum concentrations of total copper and ceruloplasmin, may be attributable to chronic cholestasis per se. This study emphasizes the clinical and therapeutic problems posed by chronic cholestasis of unknown etiology in childhood.


Lesions brought on by vomiting: the effect of hiatus hernia of the site of injury.

From an extensive review of the published cases of lesions of the esophagus and stomach brought about by vomiting and a supplemental review of local experience with the Mallory-Weiss syndrome, the influence of hiatus hernia on the lesion site can now be defined. Mallory-Weiss lesions located in the gastric cardia are commonly associated with hiatus hernia. By contrast, those occurring in the distal esophagus and those that overlie the cardioesophageal junction are only rarely associated with hernia. The Boerhaave lesion occurs most probably in the absence of hiatus hernia and in 2 of 3 previously reported cases wherein a hernia was present, a combined gastroesophageal rupture occurred. A newly recognized postemetic form of gastric rupture is clearly distinguished from other causes of this lesion and its characteristic location is described. A unifying hypothesis is proposed in which the location of lesions occurring during emesis is determined by the presence of a hiatus hernia during retching.


[Stars in mammography--cancers and radial scars (author's transl)].

Among 50 little starlike shadows in about 13,500 mammograms during the years 1973-1975 there were seven pictures proved histologically not to be cancers but "radial scars". We found no X-ray features to differentiate between scars and cancers. The uniform histologic picture of a centrally placed elastotic periductal scar with radial processes allowed however the exact differentiation. Especially significant for these radial scars is the storage of elastotic amorphous material around obliterated central ducts. Cystic atrophy or highgrade papillary epithelial proliferation in the surroundings may be combined with the central scar. Cancerous growth in this area is diagnosed without difficulty by the infiltration beyond the border of the star area.


[Negative smear in cervical carcinoma in situ (author's transl)].

In 100 patients which had shown ca-in-situ in the conization specimen during a preoperative colposcopic and cytologic investigation separate smears were taken from the anterior lip, the posterior lip and from the cervical canal. The three slides in each case have been examined to determine the frequency of negative smears, especially those of the endocervix, and to evaluate any relationship between those findings and the localization and the extent of the lesion. 22% of these patients belonged to the age group of 20-29 years, 3% were older than 60 years. Depending on the microscopic description we differentiated between small, circumscript lesions (17 cases), intracervical lesions (24) and extended lesions (59). In only 49% of the cases all three smears had been positive (Pap III-V). In 23% of the cases the endocervical smear was negative. In small, circumscript lesions at least one negative smear was found in 80% of the cases. In the extended lesions one third had at least one negative slide. In 25% of the patients with an intracervical lesion the endocervical smear was negative. Re-evaluation of the negative smears has shown an examiner's failure in about one third of these, due to several factors. In 24 patients the triple cervical smear technique had been applied at least twice. One third of the slides exhibited differences concerning negativity and positivity between the first and the second preparation.


[Prognostic factors in early endometrial carcinoma (FIGO stage I)].

The evidence concerning the most important factors related to prognosis in endometrial carcinoma stage I has been reviewed in 500 cases. Histologic differentiation of the tumor and depth of myometrial invasion have been found to be definitely correlated with survival, whereas uterine site in stage I lesions treated by hysterectomy shows no correlation between depth of uterine sounding and survival. Obesity and hypertension influence outcome in cases treated by radiation alone.


[A new obstetric forceps: the Bamberger divergent forceps (author's transl)].

A new obstetric forceps is presented which has been used since April 1975 in 52 cases for outlet forceps deliveries. The model is a divergent forceps with the rotational axis in the posterior 1/3. The forceps is applied as usual. The shanks do not cross. The distance between the blades is variable by a mechanism in the handle with an automatic stopping mechanism. Pressure on the fetal head is largely avoided. Our experience has shown that this forceps has advantages over the types of forceps in common usage.


[Isolated tortion of the fallopian tube. Report on a recurrent tortion of a hematosalpinx due to genital tuberculosis (author's transl)].

A case of recurrent contralateral isolated tortion of tubercle hematosalpinx four years after the first event is reported. The clinical picture and the pathogenesis of the isolated tortion of the fallopian tube is discussed. This disease is considered to be rare and the etiology of isolated tortion of the tube is largely unknown. As shown in this case, tortion of the tube can occur in cases of genital tuberculosis. Since acute bleeding into the fallopian tube may be pathognomonic for tortion this factor should be considered when the findings at laparotomy are interpreted. Tortion of a hematosalpinx requires additional diagnostic measures to detect the underlying disease.