The role of bronchoconstriction in cough reflex. To investigate the role of bronchoconstriction in the cough reflex, we compared antitussive effects of several drugs with their ability to effect the respiratory tract (i.e. bronchodilation vs. bronchoconstriction). Antitussive activities of five drugs administered either intravenously or orally on electrically-induced cough were evaluated in the non-anesthetized dog. The antitussive activities were as follows: morphine, 0.1 mg/kg (i.v.) and 0.5 mg/kg (p.o.); codeine, 1.0, 4.0; picoperidamine, 2.0, 9.8; piclobetol, 7.6, 9.0; HH-197, 12.5, 143.0, respectively. Morphine, codeine and HH-197 caused bronchoconstriction, but picoperidamine and picrobetol caused bronchodilation. The antitussive and bronchodilatation effects of isoproterenol were abolished by propranolol. Each bronchoconstricting drug (i.e. morphine, codeine and HH-197) was administered concurrently with isoproterenol (10 mug/kg, i.v., and non-antitussive activity), and the cough reflex was observed. Compared with the single administration of each drug, respiratory resistance was decreased and the antitussive effect was increased. These results indicate a strong correlation between bronchodilatation and increased antitussive activity.


5-hydroxytryptamine receptors in uterine smooth muscle. When studying some of the properties of 5-hydroxytryptamine (5HT) receptors in the rat uterine muscle using phenoxybenzamine (PBZ) as an antagonist it was found that the specific receptors for 5HT in the smooth muscle were selectively blocked by PBZ; a period of 20-minute exposure to the antagonist was required for maximal effect. The blockade produced was of long duration and the recovery of response was relatively slow; it was incomplete throughout the 4-hour observation period. A concentration of 1 X 10(-8) g/ml PBZ produced a parallel shift of the dose-response effects while higher concentrations reduced both the slope and maximal response. The reasons for such a shift were discussed. 5HT produced a rapid onset and offset of effect suggesting that the site of 5HT receptor is on the surface of the cell membrane. Moreover, 5HT could protect its own receptor against PBZ blockade.


The modification of inotropic action of ouabain by 6-hydroxydopamine and alpha-methyl-p-tyrosine in dogs. The action of ouabain on myocardial inotropism pretreated with 6-hydroxydopamine and alpha-methyl-p-tyrosine was studied. Inotropic action of ouabain was not changed by depletion of catecholamines in the brain, in which the central sympathetic neurons were destroyed by an intraventricular administration of 6-hydroxydopamine. Systemic administration of 6-hydroxydopamine and alpha-methyl-p-tyrosine reduced ventricular catecholamines to 5.3% and 20.8% of the control, respectively. Percent increase of contractility by ouabain after the pretreatment of 6-hydroxydopamine and alpha-methyl-p-tyrosine was reduced to 16.7% and 50.3% of the control, respectively. The results obtained suggest that catecholamines in the myocardium play some important role in producing cardiotonic action of cardiac glycosides. Brain catecholamines or the central sympathetic nervous system do not appear to participate in the exertion of the positive inotropic action of cardiac glycosides.


Effects of passive immunization with rabbit anti-phenobarbital IgG on cyclobarbital-induced sleeping time and hepatic enzyme activities of C3H mice. Effects of normal rabbit IgG (N-IgG) and phenobarbital specific IgG (Ab-IgG) on cyclobarbital-induced sleeping time were studied. Ab-IgG was specifically purified by Immunoadsorbent from rabbit antisera obtained by immunization with p-azophenobarbital bovine gamma globulin. N-IgG was purified from normal rabbit sera by DEAE-cellulose chromatography. The aggregate-free IgG were passively immunized to C3H mice 1 hr before intraperitoneal injection of cyclobarbital which has a high binding affinity to the antibodies. The pretreatment with N-IgG prolonged significantly cyclobarbital-induced sleeping time as compared with that of saline treated group, however, in the Ab-IgG treated group the duration of the sleeping was much the same as that seen in the saline group. To determine whether Ab-IgG has any influence on barbiturate tolerance, effects of N-IgG and Ab-IgG on the activities of hepatic enzymes in 9,000 X g supernatant (alkaline RNase and aminopyrine demethylase) of the mice were examined at 40 hours after cyclobarbital administration. The activities of both enzymes which could be induced by cyclobarbital were decreased significantly in Ab-IgG treated group as compared with those on N-IgG group. These results are discussed with relation to barbiturate tolerance.


Effects of polyamines on the central nervous system. Effects of polyamines on the central nervous system were studied in mice. Intraperitoneal administration of Spermidine (SPD) and Spermine (SPM) decreased spontaneous motor activity as measured by either the photo-cell counters method or the open-field test and lowered rectal temperature. A significant prolongation of sleeping time after pentobarbital was confirmed in small doses of SPD and SPM which had slight influence on spontaneous motor activity. The time to convulsion and death induced by strychnine was elongated by SPD and SPM. SPM in small doses inhibited writhing responses induced by 0.7% acetic acid. In addition, methamphetamine-induced hyperactivity and conditioned avoidance response were blocked by SPM in doses which decreased spontaneous motor activity. In all experiments, SPM appeared to have a powerful pharmacological activity compared with SPD. LD50 for SPD and SPM was 620 (500-769) mg/kg i.p. and 310 (200-480) mg/kg i.p., respectively.


Influence of various factors and drugs on cysteamine-induced duodenal ulcers in the rat. The cysteamine-induced duodenal ulcer reported by Selye et al. was investigated and the optimum conditions for the production of ulcers in rats were established. A single subcutaneous administration of cysteamine between 200 and 500 mg/kg produced ulceration in a dose-dependent manner in the duodenum within 18 hr. Female and older rats were more susceptible to cysteamine than male and younger ones, respectively. Atropine methylbromide inhibited duodenal ulcers induced by cysteamine dose-dependently and pyloric ligation immediately prior to cysteamine dosing completely inhibited ulceration. Tegragastrin or bethanechol increased the severity of cysteamine-induced ulceration. These data suggest that gastric juice may play an important role in the pathogenesis of cysteamine-induced ulcers. The present study provided an excellent animal model for studying the mechanism of duodenal ulcers and screening of antiulcer agents.


Effects of antitussive drugs on the activity of the recurrent laryngeal nerve in cats. Reflex responses in the recurrent laryngeal (RL) nerve to stimulation of superior laryngeal (SL) nerve and the effects of antitussive drugs on these reflex responses were studied in order to elucidate the site of action of these drugs in encéphale isolé cats. The RL nerve fibers were classified into four types by discharge patterns in respect to phases of artificial ventilation; type I: no spontaneous discharges, type II: discharges in phase with inflation of the lung, type III: discharges in phase with deflation of the lung, type IV: tonic discharges. Repetitive stimulation of the SL nerve elicited tonic burst discharges or short burst discharges in all types of RL nerve elicited tonic burst discharges or short burts discharges in all types of RL nerve, while the same procedure inhibited ongoing discharges of the type III and IV fibers only. The inhibited fibers tended to have slow conduction velocities (20-80 m/sec). Administration of antitussive drugs such as codeine, dextro methorphan and oxymetebanol as well as pentobarbital decreased the frequency of the after spike discharges in the RL nerves evoked following repetitive shocks to the SL nerve, but had no effects on the inhibition of RL nerve discharges evoked by the stimulation of the same nerve. The neuropharmacological implication of these findings as related to the cough reflex are discussed.


Incidence of epinephrine-induced pulmonary edema in rabbits and accompanying metabolic changes. Searching for an experimental condition to produce pulmonary edema of uniform high grade severity in rabbits, five different doses of epinephrine (38,60, 100, 160 and 260 mug/ml) were infused at a rate of 0.29 ml/min for 20 min into the femoral vein of fed and fasted animals. Body temperature was maintained at 38 to 40 degrees C. The incidence of pulmonary edema was not dose-dependent, and was approx. 70% by the administration of 60 to 260 mug/ml of epinephrine solutions. In general, the edema was more severe in the fed group than in the fasted. The highest dose of epinephrine was often fatal in the fasted group. One hundred mug/ml (approx. 10 mug/kg/min), fed was regarded as a favourable condition for the experiment. The amounts of lung lipids increased in edema (+) cases of the fed groups. The plasma potassium level was elevated in proportion to the dose of epinephrine. The clotting time of blood was markedly prolonged in edema (+) rabbits. The significance of these observations was discussed in regard to the mechanism of epinephrine-induced pulmonary edema.


Separation of cholinergic proteolipids from quenched rat cerebral cortex and resolution of properties at low temperature. Proteolipids from rat cerebral cortex quenched at -196 degrees C were extracted and fractionated at subzero temperature (-60 degrees C). On Sephadex LH-20 column chromatography, acetylcholine and cholinergic blocking agents such as dimethyl-d-tubocuratine and decamethonium were observed to bind to different fractions of proteolipids showing that the receptor fractions for acetylcholine and that for cholinergic blockers need not be the same. The acetylcholinesterase (EC 3.1.1.7) activity was demonstrated to be absent in both types of receptor fraction. The specificities of binding by cholinergic substances to proteolipid fractions prepared at -60 degrees C persisted at room temperature with some loss in specificity for acetylcholine. Since these specificities were not observed in previously reported experiments at room temperature, it appears that the structures of proteolipids extracted at the two temperatures differ. The appearance of specificities in the proteolipids prepared at low temperature suggest that their structures are in better approximation to those in vivo that presumably are highly specific. The importance of the protein moiety of proteolipids as a discriminator for the neurotransmitter is discussed.


A double column procedure for the simultaneous estimation of norepinephrine, normetanephrine, dopamine, 3-methoxytyramine and 5-hydroxytryptamine in brain tissue. A double column procedure was devised for simultaneous estimation of norepinephrine, normetanephrine, dopamine, 3-methoxytyramine, and 5-hydroxytryptamine in brain tissue. Columns of aluminum oxide were placed on columns of Amberlite CG-50 by use of a specially devised column holder so that the effluent from the upper columns could flow directly into the lower ones. Perchloric acid extracts of brain samples were passed through the doubled columns after the pH was adjusted with K2CO3. Norepinephrine and dopamine in the extracts were adsorbed on aluminum oxide in the upper columns while normetanephrine, 3-methoxytyramine, and 5-hydroxytryptamine were retained by Amberlite CG-50 placed under the aluminum oxide columns. The amines adsorbed on both columns were eluted in a small volume of dilute HC1 and each of the amines was determined fluorometrically. Some modifications were incorporated into the existing methods for developing fluorescence from the amines to increase the sensitivity. The recovery rate throughout the entire procedure for the authentic amines added to brain homogenates was in the neighborhood of 90% or higher with little column to column variation. The procedure was tested in the estimation of the five amines on various parts of single brains of normal or pargyline-treated rats.


Studies on caerulein (FI6934). Absorption, distribution, metabolism and excretion of caerulein. 35S-Caerulein (35S-FI6934) was administered intramuscularly into rats (280 mug/kg), rabbits (380 mug/kg) and mice (3.3 mg/kg). Blood level of radioactivity in rats and rabbits reached the maximum at 5 and 15 min after administration, respectively, and then decreased rapidly. In both rats and rabbits, the radioactivities were excreted mainly into the urine. The physiological activity of FI6934 was detected in the blood of rats and rabbits collected within 15 and 30 min after injection respectively, and in the bile of rats collected within the first 2 hr. In rats, the radioactivities were densely distributed in kidney, liver, pancreas, and intestine. Four metabolites of 35S-FI6934 were isolated by paper chromatography from rat urine (i.m., 500 mug/kg). The main metabolites, F-I and F-II, were negative to nynhydrin and to the Ehrlich reagent and carried no physiological activity. 35S-Chym-I, which was prepared by digesting 35S-FI6934 with chymotrypsin, was injected to rats (i.m. 16 or 8 mg/kg/. The metabolite, C-I, isolated from the urine was considered to have a very similar structure to F-I from the results of paper chromatography and paper electrophoresis. By amino acid analysis, the structure of C-I was estimated to be as follows: Pyr-Gln (or Glu)-Asp-Tyr-Thr-Gly. (see article).


Regional changes in brain catecholamine content following administration of guanethidine to neonatal rats. Norepinephrine(NE), dopamine(DA) and serotonin(5-hydroxytryptamine, 5-HT) contents were estimated in the different regions of the developing rat brain following guanethidine injection at the neonatal period for the purpose of determining the influence of guanethidine on development of the monoamine neuron in the brain. Despite a nonsignificant change in the weights of all regions of the brain, guanethidine caused a significant reduction of NE content in the limbic-striatum at day 7 and 30 and an increase in mesencephalon-ponsmedulla at day 30. DA concentration in the limbic-striatum at day 7, 14 and 30 and in the neocortex at day 7 showed a decrease with guanethedine treatment. The change in 5-HT content was not induced with guanethidine in all regions and all days examined. These results suggest that guanethidine, crossing the blood-brain barrier at the neonatal stage, induced the degeneration of the nerve terminals and "collateral accumulation" of catecholamines in the central NE and DA neurons.


Clinical studies on streptococcal preparation (OK-432) combined with mitomycin-C, 5-FU and cytosine arabinoside in advanced cancer patients. Streptococcal preparation (OK-432), a new type of anti-cancer agent, was given to the patients with advanced cancer in combination with Mitomycin-C, 5-FU and Cytosine arabinoside. OK-432 was administered intramuscularly with a daily dose of 2.0 KE consecutively or locally into the tumor with a large-dose of 100 KE. Most cases tolerated the long term administration of OK-432 without any severe side effects and the highest dose reached was 314 KE during 161 days of treatment. Of the 53 patients evaluated, 31 were given the initial large dose intratumoral OK-432. Thirteen were judged 0-C and Category 1 according to the Karnofsky criteria for a response rate of 44.8 per cent as compared with 12.5 per cent in the group without the initial large-dose administration.


Reevaluation of parasternal lymph node dissection in the treatment of mammary cancer. One hundred and forty one patients with mammary cancer underwent the extended radical mastectomy with parasternal lymph nodes dissection between January, 1966 and December, 1974. From the basis of the present report involvement of parasternaly lymph node chain was evaluated retrospectively with respect to the stage, location, size, histological type of cancer, metastasis to axillary and subclavicular lymph nodes, and the five-year survival rate. The parasternal as well as subclavicular and axillary lymph node involvements were not found in non-infiltrating cancer. The more the stage of cancer advanced, the more frequently the parasternal lymph nodes were involved regardless of the location of cancer in the breast. The parasternal lymph node chain alone was rarely involved, but frequently affected along with the axillary lymph nodes. When the parasternal lymph nodes were involved, the five-year survival rate was extremely poor, even after their surgical removal. Subsequently, addition of parasternal lymph node dissection does not seem to be beneficial.


Portal hypertension due to hepatic artery-portal vein arteriovenous fistula--a case report. A case of portal hypertension secondary to traumatic hepatoportal arteriovenous fistula with portal fibrosis was successfully treated by ligation of the afferent hepatic arteries which decreased significantly portal pressure and corrected the abnormal blood inflow to the portal vein via A-V fistula resulting in a recovery of the disturbed liver function. Collateral blood supply from the left hepatic artery into the right hepatic lobe was found to be quite satisfactory after the ligation of the hepatic artery. Hemodynamic data and clinical findings of the present case suggest that the mechanism responsible for the portal hypertension is the inflow block resulting from the interruption of portal venous flow by the inflow of arterial blood via A-V fistula and the subsequent increased blood pressure in portal vein radicals.


Occlusion of superior mesenteric artery and effect of corticosteroid in dogs. In twenty dogs the effects of superior mesenteric artery occlusion (SMAO) for two hours on several conditions likely to be responsible for the lethality of animals or men following release of SMAO were evaluated with and without corticosteroid administration. Six of ten dogs without steroid treatment died from irreversible shock within 24 hours. However, ten steroid treated dogs maintained an adequate blood pressure and survived until sacrifice 24 hours after SMAO. Release of lysosomal hydrolases, metabolic acidosis, hyperkalemia or plasma loss seemed not to have exerted important effects on the fate of animals, because their differences between the groups were not significant. Hence the mechanism underlying the beneficial effects of corticosteroid administered should be sought elsewhere.


NIH gerontology research support: policy evaluation of in vitro cell lineage studies. Populations of cultured human diploid cells, used extensively in research on aging, are not well understood in terms of kinetics and mitotic activity of constituent cells. NICHD has supported, by contract, cell lineage studies to elucidate such cell characteristics contributing to the cell population degeneration and death. The policy of NICHD (NIA) encouragment of such studies has been evaluated. A need for cell lineage and related data from cultured-cell populations is recognized, and research necessary to achieve these data will be encouraged. Grant applications to this end are sought.


Age-dependence of heat-induced strand separation of DNA in situ in postmitotic cells of rat brain as revealed by acridine orange microfluorimetry. Acridine orange microfluorimetry as well as Feulgen microfluorimetry were applied on smears of cerebral and cerebellar cortex of young (2-month-old) and old (24-27-month-old) female Wistar rats. The strand separation of DNA caused by thermal denaturation was measured between 50 degrees and 90 degrees C in the nuclei of cortical nerve cells and cerebellar granular cells. In the young nerve cell nuclei a considerable DNA-loss was observed after thermal denaturation, therefore, corresponding corrections should have been made on the heat denaturation curves. The old nerve cell nuclei of brain cortex showed a much higher heat stability than the young ones, whereas in the cerebellar granular cells the age-dependent difference was much less expressed. Our observations on chromatin in situ show the same tendency as do the findings obtained on isolated chromatin by others. The results are discussed first from a methodical point of view then the arguments are listed suggesting a possible role of interprotein cross-links in the age-dependent stabilization of the chromatin gel.


On the regeneration of aortic endothelium at different ages. In order to study the physiological regeneration of the endothelium, "Hautchen", preparations of aortic endothelium were produced from 15 rabbits of different ages and studied autoradiographically. By determining the number of 3H-thymidine-labelled cells, the mitotic rate and the total number of cells per 0.12 mm2, we arrived at the following conclusions: (1) The mean generation time of endothelial cells increases with advancing age. The extension of the mean generation time of the endothelial cells, as deduced from the decrease in the 3H-thymidine labelling index and in the mitotic rate, mainly occurs during the first four months of life. (2) Neither between topologically different aortic segments nor between such portions of the aorta as are exposed to different flow-mechanical stresses could any considerable differences with regard to the reproduction rate of their endothelial cells be detected. The raised endothelial turnover in the area of the iliac bifurcation requires further studies.


Ovarian development in athymic nude mice. The size and composition of the follicle population. Mice homozygous for the Mendelian recessive mutation nude show a reduction in the size and changes in the composition of the ovarian follicle population. Follicular loss was first evident at 2 months of age and was specifically due to a reduction in the numbers of small (primordial) follicles and medium follicles in the initial growth stages. The first ovulation was delayed until 2 1/2 months of age. By 4 months an overall reduction in all fractions of the follicle population had occurred and ovulation had ceased. These developmental changes are discussed in relation to the role of the thymus gland in sexual maturation and reproductive function in the female mouse.


Ovarian development in athymic nude mice. II. The growth of the oocyte and follicle. Congenitally athymic mice homozygous for the Mendelian recessive mutation "nude" develop well defined morphological and quantitative changes in the ovarian follicle population. A decline in follicle numbers at 2 months of age is preceded by a retardation in follicle growth at 1 month of age. The growth of the oocyte and its nucleus are not affected by the nude mutation. However, the rate of growth and maximum size of the oocyte nucleolus are reduced in nudes. These developmental events are discussed in relation to the genetic activity of the oocyte, the role of pituitary gonadotrophins in follicular and oocyte growth and the possible role of the thymus gland in these processes.


A histochemical and ultrastructural study of lipofuscin accumulation in thyroid follicular cells of aging domestic cats. Enzyme activity and fine structure of thyroid follicular cells were investigated in domestic cats at ages: 2 and 8 months, and 1, 3, 5 and 8 years. The following major changes in the follicular cells with advancing age were observed: with histochemistry--an increase in acid phosphatase and beta-glucuronidase activities confined to numerous granules (vesicles); with electron microscopy -- an increase in colloid vesicles, the appearance and increase in size and number of lipofuscin vesicles, and the increase in number of follicular cells containing numerous colloid or lipofuscin vesicles. It is our opinion that the numerous enzymatically active granules of the older groups, observed with histochemistry, are synonymous with the lipofuscin vesicles and many of the colloid vesicles observed with electron microscopy. The cellular changes involving increased enzymatic activity and lipofuscin accumulation with advancing age would correlate with decreased thyroid function reported in the literature. These observations, therefore, would suggest increased autophagic activity involving organelle or unneeded product degradation.


Biosynthesis and operating mechanism of estrogens in ovariectomized animals  under the effect of -SH groups. This paper is part of a series aimed to investigate the mechanism of the action of Folcysteine, a substance that has the capacity to release in the body active -SH groups and has been proved to be effective in the control of menopausal troubles. As an experimental model the ovariectomized rat, rather similar, from the viewpoint of the hormonal balance, to the aged female, has been considered. Under these conditions, the effect, at the uterine and adrenalian level of the treatment with two different doses of estradiol with Folcysteine alone as well as associated with estradiol, has been investigated. Our results indicate that the active -SH groups released by Folcysteine intensify the effect of estrogens upon the uterine tissue and stimulate the estrogen biosynthesis at adrenalian level.


Alteration in cellular RNAs during the in vitro lifespan of cultured human diploid fibroblasts. II. Synthesis and processing of RNA. Incorporation of tritiated uridine into cellular RNA is decreased in senescent human fibroblast cultures when measured per cellular RNA content. Since early and late passage cells demonstrate similar kinetics of RNA precursor pool labeling and saturation, this decreased tritiated uridine incorporation reflects decreased RNA synthesis. However, cellular RNA contents are markedly elevated in senescent cell cultures. When data are measured per cell number or DNA content, net RNA synthesis is slightly increased in senescent cultures. Separation of labeled RNAs by polyacrylamide gel electrophoresis revealed the same diminished specific activities (CPM/RNA) and increased net synthesis (CPM/cell number) of major ribosomal and transfer RNAs. However, this slight increase in RNA synthesis is probably not of sufficient magnitude to completely explain the observed increase in cellular RNA content in senescent cells.


Lack of erythrocyte superoxide dismutase change during human senescence. Superoxide dismutase (SOD), widely distributed in aerobic organisms, catalyzes dismutation of the superoxide free radical, O2-, to oxygen and hydrogen peroxide and apparently protects against oxygen toxicity. In human erythrocytes, O2- arises from autoxidation of oxyhemoglobin and SOD activity is copper-dependent. Since human erythrocyte copper content has been reported to decline in the fifth decade of life, we investigated the age dependence of human erythrocyte SOD activity. The mean SOD activity, assayed by inhibition of epinephrine autoxidation, was 415 +/- 66 units/g cells or 50 +/- 11 units/mg non-Hb protein. No significant difference was observed between young and old adults, and no correlations were detected with sex, state of health of the donor, or with blood hemoglobin content. The lack of general decline of SOD activity with age narrows the possible mechanisms for an involvement of O2- in senescence. SOD may yet decline in other longer-lived tissues or, as suggested by Fridovich, a constant low level of damage may be caused by imperfect scavenging of O2- by SOD. If such a mechanism is operative, it appears not to affect synthesis of SOD in erythrocyte precursor cells into the eighth decade of human life.


[The pseudolymphoma of the stomach(author's transl)]. The pseudolymphoma of the stomach can be diagnosed neither by clinical, nor by X-ray or endoscopic examination. In most cases surgery is done because gastric carcinoma is suspected, and the diagnosis of lymphoma is established upon microscopic examination of the resected specimen. In many cases complications such as bleeding, ulcers or erosions give rise to further diagnostic procedures. Prognosis is good. Surgery is the therapy of choice. 4 cases are reported and histological criteria of pseudolymphoma especially as compared to lymphosarcoma are discussed. Two different approaches are delineated in regard to ulcerative pseudolymphoma and lymphatic hyperplasia respectively.


[Melanosis coli(author's transl)].

[Melanosis coli(author's transl)]. Melanosis coli is caused by deposits of malanin- or lipofuscin-containing pigments in the colon mucosa; it is a conspicuous sign of long standing abuse of anthrachinonic laxatives. Melanosis coli can be easily diagnosed during rectoscopy, using morphological as well as histological criteria; nevertheless this condition is often overlooked or goes unnoticed. Abuse of laxatives, which is denied or concealed rather often by patients, does however explain in many cases otherwise unexplained abdominal complaints. Four cases are reported demonstrating the diagnostic significance of colonic melanosis.


[Are chronic inflammatory bowel diseases precancerous conditions?(author's transl)]. Cancer risk in patients with ulcerative colitis is higher than in patients with Crohn's disease, the reason for this difference being unknown. In ulcerative colitis the risk of malignancy justifies a prophylactic colectomy when the disease begins in childhood or in adolescence involving the total colon and lasting for more than 10 years. In Crohn's disease malignant tumors have been described in 43 cases of terminal ileitis and in 32 cases of granulomatous colitis. The cancer risk is low and does not justify a prophylactic colectomy.


Flatulent dyspepsia: a tiered symptom complex? The symptom complex of flatulent dyspepsia is ill-defined but is made up of at least nine individual symptoms. The relationship between these symptoms is not known and thier change after cholecystectomy in gall-stone patients is unpredictable; they disappear completely in less than half the patients. We studied the symptoms in one hundred and thirty nine patients, using various computer programmes to see if the changes after operation could be predicted and if some of the symptoms were linked or formed "clusters". The results did not show any standard relationship between the symptoms. We have therefore, proposed the hypothesis of a tiered symptom complex to explain these observations. They could be produced by a motility disorder affecting different parts of the gastro-intestinal tract to a varying degree.


A plea for a comparative approach to evaluation of the physiological significance of regulatory mechanism observed in in vitro studies. Regulatory mechanisms proposed on the vasis of in vitro studies using purified enzymes should be evaluated for their physiological significance in different species and under various conditions. The procedures presently employed for such evaluation are examined, and it is suggested that difficulties of application or interpretation arise, especially in studies on highly differentiated organisms. The use of comparative enzymology as an alternative approach to this problem is proposed, using in the main data obtained in studies on pyruvate carboxylase to illustrate the potential of this method. Some problems which arise in the use of comparative studies in this context are considered.


An improved method for measuring the size of myocardial infarctions. A new method is proposed for the estimation of infarction size from several measurements of creatine phosphokinase (CPK) activity. This method develops the previous method of Shell and co-workers by introducing the concept of a time- dependent fractional disappearance rate for CPK (kd(t) from the blood. This method would allow more accurate estimates to be made of infarction size.


Immune modulation and disease patterns in population groups. A hypothesis which explains disease prevalence among different socio-economic groups following early infantile modulation of cell-mediated immunity by infection and nutrition related stress is presented. Wealthy populations living under highly hygienic circumstances can develop their cell-mediated immunity to genetic expectation while their humoral systems remains unstimulated. Primitive populations protect the infant's immune development by breast feeding and suffer from temporary cell-mediated immune deficiencies due to intercurrent infectious disease and famine later on. Intermediary populations harbour a small percentage of people, whose cell-mediated immune system has been permanently damaged by infection in early childhood, leading to a high incidence of diseases linked to cell-mediated immune deficiency. The possible cocarcinogenesis of the cell-mediated immune deficiency following repeated gastroenteritis and persistent stimulation of B cells, leading to alpha heavy chain disease and primary intestinal lymphoma, or due to falciparum malaria in newborns and its impact on the EB virus genome in development of Burkitt's lymphoma, are discussed.


The sodium pump: a ghost story.

The sodium pump: a ghost story. Evidence that the sodium plus potassium activated adenosinetriphosphatase ((Na + K)-ATPase) is present and functions normally in a red blood cell ghost is summarised. The case is then argued that since ghost move neither sodium nor potassium against an electrochemical gradient, the (Na+ + K)-ATPase is not in itself sufficient to generate transmembrane gradients of sodium and potassium ions. If it is not sufficient in ghost, then it cannot be sufficient in intact cells, but most somehow work co-operatively with the cytoplasm. An alternative hypothesis to that of carrier-mediated transported is then proposed, and shown to be consistent with data on intact cells, membrane homogenates, ghosts, and membrane vesicles derived from bacteria.


A clinical trial of procarbazine plus vincristine plus bis-chloroethyl-nitrosourea plus imidazole carboxamide dimethyl triazeno in metastatic malignant melanoma. Only a limited percentage of patients with metastatic malignant melanoma respond to single-agent chemotherapy. Vincristine, procarbazine, imidazole carboxamide dimethyl triazeno (DTIC) and bis-chloroethyl-nitrosourea (BCNU) have been used as single agents by various investigators. A response rate of +/- 20% was seen with vincristine (1-3) and BCNU (3, 4), and a response rate of 20-30% has been observed with DTIC (3, 5-8) and procarbazine (3, 9, 10). Newer agents such as triazeno imidazole carboxamide mustard (TIC mustard) (11), chloroethyl cyclohexyl nitrosourea (CCNU) (12), and chloroethyl methylcyclohexyl nitrosourea (methyl-CCNU) (13) have not so far proved superior. During the last years various drug combinations have been tried in an effort to improve the results of treatment in patients with metastatic malignant melanoma. In 1959 Moon reported objective response in 9 out of 20 patients who received a minimum of two courses of a combination of BCNU and vincristine (14). In a randomized trial performed by Acute Leukemia Group B (15), only 24% responded to this combination as compared to 32% and 29% for two different DTIC schedules. There were 120 patients who entered onto this protocol. A combination of DTIC plus cyclophosphamide plus vincristine was reported to give a 25% response (16). Workers at the Mayo Clinic reported objective response in 4 out of 18 patients treated with a combination of DTIC plus vincristine as compared to 1 out of 19 using CCNU (12). Costanza and co-workers (Eastern Co-Operative Oncology Group study) reported that 12 out of 61 patients responded to treatment with DTIC plus BCNU as compared to 9 out of 51 on DTIC alone (17); while Cohen (18) and co-workers reported that 10 out of 16 patients treated with the triple combination of vincristine plus BCNU plus DTIC showed significant response and concluded that this combined approach in the treatment of disseminated malignant melanoma warranted further study. Preliminary analysis of an Eastern Co-Operative Oncology Group protocol showed no statistical advantage of DTIC plus methyl-CCNU over each drug on its own (19). The present study was undertaken to investigate the possible advantage of combining DTIC plus vincristine plus BCNU plus procarbazine in courses of treatment. All of these agents are of some value on their own and all four have possible different mechanisms of action.


Combination chemotherapy based on a model of cell recruitment by partial synchronization. A noncomparative, phase II clinical trial on chemotherapy of leukemias and solid tumors has been undertaken. It has been attempted: (a) to synchronize cells by a first administration of an M-dependent agent (vincristine or VM 26) which blocks them during the mitotic phase (M) (this has been verified by the mitotic index), from where they start again to go into the other phases of the cycle, more or less at the same time (this has been verified by the labeling index) and (b) to destroy a greater number of cells by a second administration of cycle-dependent or phase-dependent agent(s). Remarkable results have been obtained, the most interesting one being apparently complete remissions or regressions given by the sequence of two agents in patients who during previous trials proved to be resistent to both agents administered separately. The chemotherapy protocols thus composed are administered intermittently, comprising cycles with free intervals, the duration of which depends on the time of the bone marrow and blood restoration. The hematological, immunological, and visceral tolerance is, on the whole, satisfactory.


Prognosis of black children with acute lymphocytic leukemia. To assess the racial differences in survival of children with acute lymphocytic leukemia, we analyzed data for 1,675 white and 126 black children, diagnosed from 1955 to 1969. Blacks had a significantly shorter median survival and lower one-year and three-year survival rates than whites. There was substantial variation in racial differences by age. In addition, much of the variation between races seemed to be due to socioeconimic factors rather than strictly racial ones. Identification of the specific factors responsible for the poorer survival of children from lower social classes is sorely needed.


Intravenous catheter infection study: a prospective trial in patients with neoplastic disease. This study was designed to determine the frequency and significance of infection at the site of indwelling intravenous catheters. Eligible patients were randomly assigned to have an intravenous infusion utilizing either a plastic cannula or or a short metal needle. Both of these groups were further randomly divided into two groups, one having the intravenous catheter removed every 48 hr and the other having the catheter changed only when necessary. One hundred and eighty-seven catheters from 50 patients were cultured. Eleven (5.9%) of the catheters were found to be colonized by organisms. Metal needles and plastic cannulas were infected with similar frequency. The incidence of local infection was not influenced by concurrent antibiotic therpy, local phlebitis, or the level of the granulocyte count during the period of intravenous infusion. Six of 31 catheter tips in place for longer than 56 hr were colonized by organisms, compared with 5 of 156 catheter tips in place for less than 56 hr (p less than 0.0001). The study indicates that indwelling intravenous catheters should be changed at least every 48 hr in order to prevent colonization of the tip of the intravenous catheter.


Response of 65 measurable epidermoid bronchogenic tumors of known spontaneous doubling time to four different chemotherapeutic regimens--strategic deductions. Variations in the dimensions of 65 bronchogenic epidermoid tumors of known spontaneous doubling time were studied under the influence of four chemotherapeutic regimens: cyclophosphamide, 19 cases; Mitomycin C, 20 cases; CCNU, 9 cases; and a five-drug combination, 17 cases. Several parameters were measured, and escape was defined as the moment in time when the growth curve during treatment became parallel to the spontaneous growth curve. The parameters measured were nature and distribution of responses (unchanged progression, slowing-down, plateau, regression), duration of response, time required to achieve maximum response, and time lapse between maximum response and escape. Regarding application to lung cancer, we have concluded from out results that Mitomycin C should replace cyclophosphamide in combination chemotherapeutic regimens. With regard to general strategy, our results suggest that the drug regimen should be changed as soon as maximum response is reached or immediately following the first course if progression continues unchanged. Moreover, in all of the 27 patients whose tumors regressed, escape occurred within less than three months from the onset of the treatment. In view of this fact and insofar as chemotherapy is considered for adjuvant therapy aiming at complete eradication, sequential combinations would be preferable to prolonged administration of a single agent or combination.


[DNA fusion in the presence of catecholamines and substances close to them in structure]. Using an Cphi-4A spectrophotometer (USSR), denaturation of DNA containing approximately 2% residual protein has been studied in the presence of catecholamines and their precursors: epinephrine, beta-3,4-dioxyphenylalanine, norepinephrine, 3,4-dimethoxyphenylethylamine, tyrosine, and phenylalanine. All these substances, excluding phenylalanine, induce positive excessive hyperchromicity (as compared to initial DNA). The correlation between this effect and molecular structures of the substances studied has been shown to exist. An increase of DNA hyperchromicity in the presence of catecholamines has been found to result from the oxygen presence in the aromatic rings of the catecholamines molecules. It is assumed that the interaction between the negative O-atoms in catecholamines and bivalent metal cations in the nucleoprotein complex weakens the DNA-protein binding. This leads to an additional disorientation due to the heat of nucleic acid bases, which were previously bound by the residual protein.


[A theoretical conformational analysis of several substrates of cholinesterase having a cyclic ammonium group structure]. Conformational possibilities of pirrolidine analogues of acetylcholine beta-(N-methyl pirrolidinium)-ethyl ester of acetic acid and beta-(N-ethyl pirrolidinium)-ethyl ester of acetic acid and beta-(N-ethyl pirrolidinium)-ethyl ester of acetic acid were investigated by the method of atomic potentials. The conformational energy was considered as a sum of non-bonded and electrostatical interactions, torsional energy and distortions of bond angles. It has been shown that the replacement of the nitrogen methyl group to ethyl group results in decrease of the average barrier height between two gauche conformations of the O--C--C--N fragment. Comparison of conformational properties of some cholinesterase substrates permit to draw a suggestion that the barrier height influences the rate of the enzymatic hydrolysis.


[The interaction between newly-formed mRNA and ribosomal particles during retarded translation]. The formation of polyribosomes in mouse liver cells at the reduced-rate translation was studied by treatment with cycloheximide (CHI) and aurintricarboxylic (ATA) acid. An increase of polypeptide synthesis time by 1.7-2.7 times (0.5 mg CHI per 25 g of weight or 15 mg ATA per 25 g) leads to a delay of the entrance of newly formed cytoplasmic D-RNA into polyribosomes. These results are in agreement with the model of polyribosome formation from ribonucleoprotein precursors containing cytoplasmic D-RNA. On the other hand, in the presence of a CHI dose (5 mg/25 g) causing a dramatic (240-fold) increase of polypeptide synthesis time, the kinetics of entrance of newly formed D-RNA into polyribosomes does not differ from the normal one, and amount of the incorporated mRNA is even somewhat higher than under normal conditions. It is suggested that in this situation ribosomes are moving along the newly formed mRNA, and their movement is not accompanied by the synthesis of completed polypeptide chain.


[The effect of acridine dyes on the molecular structure of DNA]. DNA--acriflavin complexes have been investigated by the methods of flow birefringence and viscometry. The intrinsic viscosity and the optic anysotropy of the complex increase with the increasing quantities of binding dye. Experimental data are treated on the basis of different models of binding. At high ionic strength (mu = 0,1) one type of binding takes place which is described by the intercalation model. In this case the thermodynamic rigidity of DNA-molecule within the complex is proportional to "r". In solutions of low ionic strength (mu = 0,001), two types of DNA-acriflavin binding occur: intercalation and external binding. At low ionic strength, the spectrophotometric titration technique is shown to give a reduced value of "r".


[Fusion of complexes of DNA and extended ligands]. The theory of melting of DNA complexes with extended ligands (ties) is considered. Influence of ties interacting electorally with certain DNA regions and influence of extender ties, interacting unelectorally on the helix coil transition parameters is compared. It has been shown that both types of ties cause, coincided qualitatively, but differed quantatively, shifts of melting temperature and change of the melting range width of DNA. Comparison of theory with experiment in the case of DNA complexes with ribonuclease is given.


[Ribonucleoproteins containing mRNA in the cytoplasm of mouse plasmacytoma cells]. The rapidly labelled postribosomal ribonucleoprotein (RNP) found in the cytoplasm of mouse plasmacytoma cells were investigated. It has been shown that 45S and 80S particles contain relatively high molecular weight (approximately 12-17S) pulse-labelled RNA similar to the polyribosomal mRNA. No other postribosomal RNP was found which would contain an RNA with similar sedimentation characteristics. In CsC1 density gradients, the postribosomal RNP gives two peaks. One of them, the rapidly labelled component (rho 1.52 g/cm3) is found only in 45S RNP. The other rapidly labelled component (rho 1.36-1.41 g/cm3) is revealed in all investigated regions of sucrose gradients. The latter contains relatively low molecular weight RNA (approximately7-9S). These RNP are supposed to be informosome-like particles. The components with a buoyant density of 1.52 g/cm3 may represent an mRNP-45S subparticles complex. The rapidly labelled mRNA of 80S particles is released after EDTA treatment in the form of mRNP with a buoyant density of 1.45-1.47 g/cm3.


[Reorganization of national health services in England-an event worth knowing by world health professionals]. Based on the experience gained on the study tour through Great Britain, authors present their observations on health service in this country. A direct reason for the study tour was a desire of Great Britain to provide to health care planners of other countries an insignt into the status of health care system resulting from the last reorganization in 1974. In the introductory part, presented are essential data on health service and a review of basic concepts. A special emphasis is given to the uniformity of the service, provision of comprehensive care as well as to an encouragement of general practitioners to take central positions in the united health service. Further, details on reorganized system and an evaluation of these changes are presented. Shown are data on rationality of service and through a comparison with other countries it is concluded that health service of Great Britain is probably most rational in the western hemisphere. Finally, authors express their belief that further advancement and organizational improvement of the service will be made.


[The influence of proteins bound to single-stranded DNA on RNA and poly(A) synthesis. I. Antibodies against DNA]. The influence of antibodies to DNA of T4 and SPOI phages as well as to DNA of E. coli on RNA and poly(A) synthesis by E. coli RNA polymerase has been studied. Antibodies to the phage DNA specifically inhibit RNA and poly(A) synthesis by 30 to 60% only in case of homologous DNA, the stage of elongation being inhibited predominantly. A comparison between the effects of the antibodies upon different stages of RNA synthesis on the native DNA and on the synthetic oligonucleotide template (dT)12 allows to draw a conclusion that upon inhibition of the synthesis the antibodies interact with a single-stranded site of the template not covered with RNA polymerase molecule, this site being formed during transcription of double-stranded DNA.


[Posterior osteosynthesis in the treatment of spinal cord tumors]. Prognosis of cancerous tumors of the spine depends above all on their neurological consequences. The authors have wondered whether osteosynthesis of the spine -- in addition to decompressive surgery -- can improve patient's survival and fonctional results. 23 patients, 20 with a metastatic tumor and 3 with a plasmocytoma were treated in this way. All of them had neurological deficits, 4 had isolated radicular symptoms, 1 a cauda equina syndrome and 18 a spinal cord compression (7 of which were complete). 20 of these patients suffered intractable pain of the spine. All the patients underwent decompressive surgical removal of tumor through laminectomy, associated with a bilateral posterior metallic osteosynthesis. The type of osteosynthesis consisted of two metallic plates placed along each articular column and screwed into the articular processes and the vertebral body through the pedicles of the adjacent normal vertebrae. Cobaltotherapy was added in 14 cases, hormonotherapy in one case and radioactive 131 1 in one another patient. Selective spinal angiography, performed in one case of thoracolumbar tumor was found useful in the location and avoidance of Adamkiedwicz's artery. With regard to the complication, there were two operative wound infections requiring reoperation. Our series -- in comparaison with others -- prove the effectiveness of the combined procedure. Patients without complete spinal deficit had a 20 months survival average. Patients with complete deficit had the same survival as in comparative group. But all the 20 patients suffering pain in the spine were substantially relieved. Such a combined procedure is indicated in cases of tumors involving the vertebrae, whether or not the epidural space is invaded especially when there are riskes of unstable fracture and only partial neurological deficits. The technique may be extended even to complete paraplegia because of its worth while antalgic effects. Thus this method -- by consolidating the spine -- relieving pain and consequently allowing kinesitherapy to be resumed earlier is able to improve the functionnal status and increase survival of the patients.


[Prognostic elements at early stapes of severe spinal cord injuries (value of pain sensitivity]. The prognosis in serious spinal cord injury remains difficult. The neurologist has a large number of elements at his disposal, but their reliability is uncertain. Clinical information, experimental work and recent data on medullar vascularization makes it possible to isolate diagramatically in the spinal cord a medium layer which contains the pyramidal and spino-thalamic tracts. The neighbourhood of these two fasciculi confers them a similar vulnerability to severe injury. Thus when an injured tetraplegic or paraplegic patient recovers his sensitivity to pain, he finally must recover his motor function and on the contrary, the recovery of motility is impossible without a return of pain sens. Clinical observation is in consequence of major importance as it shows that the recovery of sensitivity to pain, in the case of a patient with a serious spinal cord injury, is an argument for a favourable prognosis, whereas the recovery of an isolated tact perception does not in itself makes it possible to hope for eventual recovery of motor power.


[The neurosurgical forms of Hurst's acute hemorrhagic leukoencephalitis]. Within the group of acute encephalitis, H.A.H.L. is individualized mostly by its post mortem pathology. But several cases of recovery were recently published, the diagnostic being based on biopsy material. In 4 of our 8 cases, a comparison between the biopsy and post mortem examinations was possible : in/the diagnostic of H.A.H.L. was unequivocally confirmed, in 2 H.A.H.L. is nearly certain, in 1 it is doubtful. These considerations do not contradict the necessity of an emergency brain decompression in many instances of acute encephalitic states.


[Pneumographic signs of poorly compensated hydrocephalus]. A definition of "Hydrocephalus not completely arrested" is not easy to be given. Cerebral pneumography represents the most detailed neuroradiological examination. In spite of this, neither its analysis nor its measurements bring definite criteria for the favorable moment of locating a shunting system in that case. These criteria are reviewed systemetically. It is pointed out that only a careful synthesis of all signs can give a univoque answer, may be doubtful but never wrong. It is suggested from the personal experience that radioisotope cisternography is better suited for judging the state of compensation of an hydrocephalus. Radioisotopes do that without undue risks. It may be  but one good reason for explaining the annual decrease in the number of pneumo-encephalographies (PEG) registered almost everywhere in the world. Other factors may be involved. No doubt that PEG has lost its first place in the study of patients who may have some kind of non tumoral hydrocephalus.


[Variations of the cerebral blood flow after hyperbaric oxygenation in traumatic coma]. We have previously shown (Ref. I) the absence of variations in average cerebral blood flow, measured by the method of LASSEN, following treatment of traumatic coma by means of hyperbaric oxygenation patients presenting with brainstem contusion, during 2 hours of HBO (at 2.5 times atmospheric pressure) measurements of cerebral blood flow were made using a single detecting probe, before and two hours after terminating HBO. Measurements in 9 patients demonstrated variations in cerebral flow greater than predicted by experimental error (+/- 4%): 5 measurements (these with initial flow less than 31 ml/mn/100 g increased following OHB, while 4 measurements (these with initial flow greater than 31 ml/mn/100 g) decreased following OHB. In order to determine the significance of these variations, we studied the correlation between two methods of calculating cerebral blood flow : the exponential (bicompartimental) method, and the stochastic method, assuming lambda the coefficient of partition, tobe equal to I. These two method of calculation appear to be independant ; thus, the observed correlation (r = 0.74, p less than 0.01) tends to validite the measured variations in flow. This finding is further supported by the calculated correlation between the change in flow as measured by the exponential and that measured by the stochastic method (r = 0.684, p less than 0.05). Thus, we feel that measured changes in flow represent changes in cerebral perfusion, and cannot be attributed to the method of calculation. The bio exponential method of calculation of flow, D = Dg + Dw (with Dg = fg. Wg = "index of grey perfusion" and Dw = fw. Ww = "index of white perfusion", where fg = lambda1. (see article), and where Wg and Ww represent the percentage of the grey and white substance) permit calculation of a highly significant correlation between the change in flow and the grey perfusion index (r = 0.83, p less than 0.01). This correlation, previously described in the literature, appears to explain the observed findings in terms of the variations in perfusion of the grey compartment. However, there exists an equally significant correlation, but negative, between the variations of the grey and white perfusion index (r = 0.824, p less than 0.01). This correlation seems to indicate the presence of an inverse relationship between flow to grey and white substances, tending to minimize the variations of the total flow after OHB. We can then formulate an explanatory hypothesis: if one assumes that the diminution of intracranial pressure during OHB, by decreasing cerebral edema, hastens the recovery of perfusion in the damaged zones, then the response to therapy with hyperbaric oxygenation should differ, depending on whether the tissues were healthy or damaged. Healthy tissues should show a decrease, while damaged zones should show an increase in flow following OHB. This mechanism would appear to explain, in relation to lesions located predominantly in grey or white matter, the observed negative correlation between blood flow to the two compartments.


[Unrecognized aneurysms of the circle of Willis]. The authors present, among 200 intracranial arterial aneurysms, 13 cases where the angiographic diagnosis of the aneurysm had been difficult. Among them, there were ten mistakes through default, and four mistakes through excess. Angiographic studies were done early, about the third day following subarachnoidal hemorrhage, so that conscious patients may have rapid surgery. The main diagnosis defaults were observed in aneurysms of the anterior communicating artery (cases 1, 2, 3, 4, 6), where the flexurae and arterial anomalies explain the diagnostic mistakes; double anterior cerebral artery, median anterior cerebral artery of Lazorthes, early origin of the frontopolar artery or of the callosomarginal artery. The aneurysms of the posterior wall of the carotid bifurcation, were hidden by this artery in the A.P. view and by the middle cerebral artery in the profile view (cases 5 and 7). Oblique views are necessary for the two localizations of these aneurysms. The middle cerebral aneurysms (case 8) may be hidden by a bony superposition. The Ziedses des Plantes subtraction method obviates this diagnostic default. Aneurysms of the peripheral branches of cerebral arteries (case 9) are filled later and slightly. Aneurysms of an artery less than 3 mm wide (posterior communicating artery, lenticular artery) are difficult to discriminate from their enlarged infundibulum (case 10). The small size of the aneurysm is not the only explanation of the difficult diagnosis. Indeed, few aneurysms are not evidenced by the first angiography, done at an early stage, even if any spasms exist. Only repeated angiographies could show the aneurysm particularly in young people. We repeat the angiography 15 to 20 days after the first one, and even some months later. In two young patients, angiographic studies were repeated a few times in three years and were normal; but after four years in one case and five years in the other, a new subarachnoidal hemorrhage occurred, and only then was the aneurysm shown by a new angiography (cases 4 and 5). In our series, the angiographic spasm could not afford an explanation for the diagnostic default. This, soon after the subarachnoidal hemorrhage, might be explained by the hemostatic clot which compresses or plugs the aneurysm. Further, the clot's lysis occurs, and the aneurysm can be evident. A double conlcusion must be drawn: --first, the angiography must be repeated if the image is dubious; the angiographic technique must be perfect and varied (oblique view, subtraction method, enlargement technique). Mistakes through excess, leading to useless operations, are as dangerous as mistakes through default; --secondly, great care should be exerted when reading and interpreting the X-ray films in the post-operative period in order to evaluate the surgical results, as well as in the preoperative period.


[Traumatic obliteration of the middle cerebral artery. Pathogenic considerations]. Report on one case of traumatic obliteration of the middle cerebral artery together with a review of the pathogenetic theories published till presently on this subject. Three factors are retained in the case object of the present work: --compression of the arterial wall in the Sylvian fissure, as a consequence of contusion and cerebral edema, --disorders in the platelets aggregation, --high blood pressure.


[Frontobasal injuries and csf fistulas. Attempt at an anatomoclinical classification. Therapeutic incidence]. The authors present a classification of trauma to the cranial base, based on observation in 80 cases. There are five types. Type I : involves only the anterior wall of the frontal sinus. Type II : involves the face (craniofacial disjunction of the Lefort II type or crush face) and extend upward to the cranial base and, in occurency, to the anterior wall of the frontal sinus, because of the facial retrusion. Type III : ivolves frontal part of the skull and extend down to the cranial base. Type IV : is a combination of types II and III. Type V : involves only ethmoidal or sphenoidal bones. Cerebrospinal fluid leak is unfrequent in types II, and transitionnal, if it occurs ; but it often occurs in types III, IV and V which include in every case a dural tear. Correct diagnosis facilitates treatment. Fractures of types I and II can be fully treated by maxillo-facial surgeons, whereas for types III, IV, and V, they need the help of a neuro-surgeon.


[Nephrographic study with 131 iodine hippuran in surgical diseases of the uropoietic apparatus]. Personal experience with 131I-Hippuran nephrography, particularly in surgical cases, is described. The examination is a useful aid to the diagnosis diagnosis of recent colic and in the investigation of cases where a negative finding has been obtained with other radiological means. Its pre- and post-operative employment in the evaluation of renal function is also discussed.


[Statistical analysis of correlations between tonsillectomy and malignant neoplasms of the thyroid]. An analysis of correlations between tonsillectomized patients with thyroid cancer and a control group with respect to sex, histological type and blood group did not throw up anything of statistical significance. Of great statistical significance, however, was the age factor in sufferers from malignant cancer, whether or not their tonsils had been removed; in fact tonsillectomized subjects were affected by malignant cancer at a younger age than those who had not undergone the operation. It is concluded that, at the moment of greatest immunological production, the tonsils seem to represent a barrier to the onset of malignant cancer in general, and thyroid types in particular.


[Statistical notes on the age and survival of 178 patients operated for malignant breast tumors]. Age and survival data in a series of 178 patients operated for malignant breast tumour during the period 1957-67 are statistically assessed. The mean survival period was 9 yr. Young subjects had a greater chance of survival, while their mortality rate was the lowest after the fifth year.


Combined modality therapy for localized Hodgkin's disease. A seven-year update of an early study. Some clinical trials have indicated that combination therapy with intensive radiation therapy followed by chemotherapy significantly prolongs the disease-free interval of patients with Hodgkin's disease confined to lymph nodes. The present report updates the results of a small previously published study of combined-modality treatment of stages I and II Hodgkin's disease. Although patients tested with radiation therapy followed by chemotherapy have the longest median complete remission duration, patients treated with radiation alone have a superior survival rate. Follow-up in this study ranges from 34 to 93 months after the completion of all therapy.


Hydrazine sulfate and preneoplastic exfoliated cells. Animal experiments and most encouraging clinical trials substantiate that hydrazine sulfate inhibits the paraneoplastic systemic energy-losing cycle. The question arises: could hydrazine sulfate offer an alternative to surgery for patients with preneoplastic exfoliated cells? Research data indicate that clinical trials are appropriate.


Redistribution of radiocolloid uptake after focal hepatic radiation. A woman with colonic carcinoma metastatic to the liver received 2,200 rad external beam radiation to the right hepatic lobe. A repeat liver scan, 2 months after conclusion of radiation therapy, showed a shift in the distribution of radiocolloid uptake to the left lobe and spleen. This altered pattern was likely related to the large volume of hepatic tissue included in the radiation portal, with damage to the radiated area. The clinician must be alert to abnormalities induced not only by neoplastic disease, but by the therapy utilized.


A study on delayed hypersensitivity aspects of immune response in patients with carcinoma of bronchus in relation to radiotherapy. Results of a preliminary study on the delayed hypersensitivity aspects of immune response in 45 patients with carcinoma of bronchus revealed by sequential skin testing are presented. Short-term prognosis and the immune reactivity thus studied appear to be well correlated. Anergy before treatment and allergy changing to anergy following radiotherapy tend to be associated with grave prognosis and conversely persistently allergic patients fare better at least on short-term prognosis. Contrary to the usual impression that  radiations are immunodepressant, this study reveals increased skin tests reactivity following radiotherapy in 7 out of 17 immunocompetent patients. Recent literature on human and animal studies appear to support this phenomenon of increased immune reactivity in certain situations following radiotherapy and chemotherapy. The few publications are reviewed. A much more elaborate controlled in vivo and in vitro study is now underway to reveal the immune profile of patients with cancer particularly in relation to radiotherapy.


The ribosomes of the Novikoff tumor cells: isolation, general properties and electrophoretic analysis of the protein moiety. The ribosomes from Novikoff tumor and rat liver cells were extracted, purified and analyzed. The isolated ribosomes are active in Poly-U directed Poly-Phe synthesis. Sucrose density gradient centrifugation showed that the Novikoff tumor cells contained, in contrast to liver cells, almost no polysomes. The ribosomal proteins from the ribosomes were extracted and subsequently analyzed by gel electrophoresis. No differences between the ribosomal proteins of the normal and neoplastic cells could be detected by one-dimensional sodium dodecyl sulfate gel electrophoresis. Two-dimensional urea gel electrophoresis showed great similarities between the ribosomal proteins of the two kinds of cells. However some differences could be detected.


Effects of selected sulfhydryl inhibitors on nonhistone chromosomal proteins of HeLa cells. Effects of the SH inhibitor sodium iodoacetate, alone and with adjuncts menadiol diphosphate, sodium malonate, sodium fluoride and heparin, on incorporation of tryptophane-3 H into nonhistone chromosomal proteins of HeLa cells were examined. The drugs block incorporation of tryptophane-3 H into nonhistone chromosomal proteins far more than incorporation of leucine-3 H into total cellular proteins. Drug effects on thymidine phosphorylation and DNA synthesis in HeLa cells exceed corresponding effects on fibroblasts from normal healing wounds.


A critical analysis of xeroradiography of the breast. Xeroradiography is a process that utilizes an electrostatically charged selenium-coated aluminum plate to record the radiographic image instead of the familiar X-ray film, and employs the same basic principles of positioning and exposure technique used in conventional film mammography. The latent image of charges remaining on the selenium plate after exposure to X-rays is developed with a coating of blue toner powder, and transferred to a special plastic-coated paper for interpretation and permanent storage. Resolution in xeroradiography is adequate and, combined with the characteristic edge enhancement, allows clear visualization of the fine internal structures of the breast. Xeroradiography is proposed to have the following advantages over film mammography: easier to interpret, requires less radiation, greater detail, a more rapid, easier, dry developing process, and is probably more accurate. Reports from several centers of xeroradiography reveal increased confidence in mammographic interpretation and in increase in the diagnosis of minimal breast cancers.


Morphological alterations induced in organ cultures of human fetal trachea and bronchi by diethylnitrosamine (DEN). Human fetal respiratory tract was exposed to the action of N-nitrosodiethyl-amine (DEN), a potent carcinogen for other species, in a organ culture system. The dose of 15 mul/ml DEN elicited an intensive proliferative response of the respiratory epithelium while higher doses were toxic.


Inducing tumor immunity by specific tumor antigens. A handy experimental model for testing anti-tumor agents and for studying tumor immunity is the use of Walker 256 carcinosarcoma in Long-Evans hooded rats. This neoplasm is so easily transplantable and growth is so rapid that a large series of animals can be studied in a relatively short period of time.


Quantification of CEA in human gastrointestinal cancers grown in in vitro long-term organotype culture. Two malignant tumors of the human gastrointestinal tract (obtained surgically) have been cultivated in vitro in long-term organotypic tissue culture. Of these line AZ110 (maintained for 6 years) originated from a primary adenocarcinoma of the ascending colon, whereas line Z200 (grown for 14 years) originated from a hepatic metastatic nodule of a gastric adenocarcinoma. Extracts of these tumors and comparable surgical specimens were evaluated quantitatively for carcinoembryonic antigen (CEA) using radioimmunoassay. Both cultured lines exhibited CEA levels that were somewhat higher than comparable surgical specimens.


Skeletal effects of cholesterol feeding. The effect of a 4% supplement of cholesterol to a standard diet on knee joints and vertebral columns was investigated in male mice of strain C57B1. The experimental diet was fed from the time of weaning through the 18-month period of observation or from the age of 1 year to the end of the experiment at 18 months of age. The incidence of osteoarthrosis was increased in mice fed cholesterol from the age of 12 months on. The incidence of spondylosis was increased after lifelong feeding as well as after feeding of cholesterol during the second year of life. This increase involved both, spondylosis associated with or uncomplicated by prolapse of intervertebral discs. The incidence of simple disc prolapse was not affected by the experimental diet.


Presence of HBsAg in the bile of subjects with acute HBsAg viral hepatitis. During acute HBsAg serum positive viral hepatitis, the surface antigen was not detectable in duodenal bile but was almost always present in gallbladder and hepatic bile when cholecystokinin was intravenously administered. The immunologic nondemonstrability of HBsAg in duodenal bile is probably due to the presence of a factor elaborated by the intestinal mucosa. The possible role played by this factor in the non transmission of type B viral hepatitis via faecal-oral route is suggested.


Some serum biochemical changes associated with chloroform-induced renal tubular necrosis in mice. The chloroform--induced renal tubular necrosis is associated with the rise of serum urea, creatinine and potassium. The highest values, observed 24 hours after chloroform administration, are respectively: 75 mg% (norm 32 mg%), 1.75 mg% (norm 0.25 mg%), 6.1 mEq/1 (norm 4.4 mEq/1). They gradually decreased with the progress of renal regeneration. These transient, rather little biochemical deviations justify the good conditions and eventual survival of chloroform-poisoned mice. The contribution of possible glomerular lesions to the disturbed renal function is taken into consideration.


Histological studies on the regeneration of small-intestine epithelium of rats irradiated with sublethal doses of X rays. The dynamics of regeneration of small-intestine epithelium was studied in rats irradiated with X-rays in sublethal doses of 550, 600 or 750 R. Sixty-two irradiated and 22 control animals were used in the experiment. They were killed 1,2,4,6,8,14 and 25 days after the irradiation. Specimens of duodenum and jejunum were examined histologically, the sections being stained with H.E. and p.a.S. Already 1 and 2 days after irradiation the intestinal villi became shorter and deformed. The blood vessels were damaged, the enterocytes showed features of degeneration and vocuolization, the epithelium was detached by the exudate which accumulated in the stroma. Irradiation markedly disturbed the regeneration of intestinal epithelium in the period from the 1st to the 6th day. Cytological calculations indicate that on the 1st and 2nd days after irradiation the number of epithelial cells of the villi, and particularly of young cryptal ones, markedly dropped. On the 4th and 6th days increased proliferation of young cryptal cells considerably surpassed the physiological rate. The accompanying disturbances in differentiation consisted in a decreased acidophilic to basophilic cells ratio and in retardation of maturation of goblet cells. The absolute number of goblet cells was increased, as well as their proportion to the number of enterocytes.


Significance of serum lipoproteid-X (LP-X) determination for the diagnosis of cholestasis in chronic liver diseases. Among 179 patients with various chronic diseases of the liver the authors found in 20 cases histological evidence of intrahepatic cholestasis and in all these cases lipoproteid X (LP-X) was present in the serum. In the group of 159 patients without evidence of cholestasis in microscopic examination of liver tissue LP-X was demonstrated only in two cases (1.3%). The results of investigations confirm the view that detection of LP-X in the serum is a specific and sensitive index of cholestasis and its value in the diagnosis of this condition is greater than that of determinations of alkaline phosphatase, gamma-glutamyl-transpeptidase, leucinamino-peptidase activity or cholesterol in the serum.


Effect of low-magnesium diet on the histology and the activity of certain enzymes of rat myocardium. Rats kept on a low-magnesium diet for 14 weeks developed increasing clinical symptoms, from slight trophic changes to inhibition of growth. Focal fragmentation of myocardial fibers was followed by focal fuchsinophilia and later--by focal necrosis. Increasing morphological lesions were associated with calcium salts deposition in the degenerated myocardial fibers, connective tissue and wall of cardiac blood vessels. The low-magnesium diet did not affect the activity of ATP-ases and cytochrome oxidase. The areas of myocardial degeneration and necrosis were free of the activity of alkaline phosphatase and succinic dehydrogenase.


Blood fibrinogen level in peptic ulcer and gastric carcinoma. The plasma fibrinogen levels were determined in patients with chronic gastric and duodenal ulcer and gastric cancer comparing the results with those in a control group comprising healthy subjects. No statistically significant rise in the level of fibrinogen in peptic ulcer or its changes during treatment were found. A great rise in the blood level of fibrinogen was observed in 67% of cases of gastric cancer.


Studies on the behavior of lymphocytes in the direct lymphocytotoxicity test (DLT) in surgical patients: I. Diagnostic value of the test. The results of the investigations of immunological reactivity in 120 surgical patients are presented. The direct lymphocytotoxicity test (DLT) was used. Negative results were found in only 20 patients; in the remaining 100, the number of damaged lymphocytes in the peripheral blood, examined in vitro was dependent on: 1) the type of surgical procedure (e.g. open reduction and internal fixation of long-bone fractures), 2) severity of surgical disease, 3) interaction of drugs used, and 4) infection, most probably viral. A high percentage of damaged lymphocytes was found firstly, in patients suffering from severe wound infections; secondly, in those with disorders of the peripheral arteries during the postoperative course and thirdly, in patients with advanced malignancy of the alimentary tract. The results of these investigations--regarded by the authors as a preliminary report--indicate that the DLT could be introduced routinely as part of pre- and postoperative examinations of surgical patients in order to evaluate their immunological reactivity.


Regulation and grinding ability of grit in the gizzard of Norwegian willow ptarmigan (Lagopus lagopus). Fluctuations in grit composition in the gizzards of willow ptarmigans and the grinding ability of various grit assortments from wild ptarmigans were examined. We confirmed reports of other investigators that larger, fewer and rounder stones were present in the winter than in the autumn. Experiments showed that ptarmigans prefer stones with diameters between 2-5 mm. Birds on a constant diet maintained a constant stone intake throughout the year. The composition of gizzard grit was influenced by the availability of stones as well as of the type of food the ptarmigans ate. Using an artificial gizzard, grit from birds shot during the autumn was found to be a more efficient grinding material than grit from winter birds. We suggest that other functions than grinding, such as  supplying minerals, may be equally important functions of the grit.


Combining ability in a diallel cross of three lines of Coturnix coturnix japonica. Three random-bred lines of Japanese quail were crossed in a 3 X 3 diallel to estimate their combining ability for hatchability, growth rate, and age at 25, 50, 75 and 100% lay. The experiment was conducted as a randomized complete block design with a 3 X 3 X 2 X 2 factorial arrangement of treatments (3 lines of sire X 3 lines of dam X 2 ambient-temperature stresses X 2 sexes). Approximately 1200 eggs in three hatches were set; 496 progeny measured for five week body weight; and 212 hens observed for age at maturity. General combining ability effects were highly significant for percent hatchability. Specific combining ability was not important for hatchability in the three lines tested. Data on body weight revealed highly significant effects due to general combining ability, specific combining ability, sire X sex interaction, hatch, ambient-temperature stress and sex. Data for age at 25, 50, 75 and 100% lay indicated that general and specific combining abilities as well as maternal effects were all highly significant.


Activity of lysosomal enzymes and glycogen content of phytohemagglutinin-stimulated lymphocytes in patients with rheumatoid arthritis. In patients with rheumatoid arthritis and in healthy controls a continuous rise in acid phosphatase activity was observed in PHA-stimulated lymphocytes and the activity index was higher in patients than in controls. Differences were also observed between these groups in the activity of nonspecific esterase, beta-glucuronidase, and glycogen content at different hours of culture.


Photoacceleration of embryonic development in depigmented Japanese quail eggs. Pigmented and depigmented Japanese quail eggs were incubated either in the presence of a light source for one week or in the dark. Acceleration of embryonic development was apparent by the first day of incubation in the depigmented eggs exposed to light. Embryonic weights of eggs exposed to light were significantly (P less than .05) greater than eggs incubated in the dark by the fourth day of incubation. Air cell temperatures of depigmented eggs were significantly (P less than .05) lower than pigmented eggs by the fourth day of incubation when both groups of eggs were exposed to a light source. Thus photoacceleration appeared to be a real effect, and great enough to overcome the lower egg temperature at which these embryos developed. Embryos developing in lighted depigmented eggs can decrease the hatching time of other groups incubated with them.


Electron microscopic lesions of supraoptic and para-ventricular nuclei of rat thalamus in adrenal insufficiency. Ultrastructural changes in the supraoptic and paraventricular nucleus of the rat brain in adrenal hypofunction evoked by bilateral adrenalectomy are described. Marked ultrastructural changes were observed in the ultrastructure of the neurons of the paraventricular nucleus, the changes being less pronounced in the suproaoptic one. The changes indicated enhanced synthesis of neurosecretory granules activating the so-called "creation" surface of the Golgi complex. The increased synthesis of neurosecretory granules in adrenal hypofunction might indicate that some of them could be CRF carriers. It is not possible, however, to find by exclusively morphological methods the morphological equivalent of CRF. The higher intensity of the changes found in the paraventricular nucleus suggests that the latter possibly plays a more important role in the regulation of ACTH secretion.


Dietary calcium levels in pre-lay and lay diets in Leghorn pullets. Four experiments over a period of four years with 1350 first-year pullets were designed to determine the influence of the calcium and phosphorus levels in the pre-lay diets on the growing birds and on their subsequent performance. Several dietary calcium levels in the lay period were studied, as well as the interaction between the pre-lay and lay diets. During the growing phase the pullets fed 3.0% calcium and 0.4% phosphorus had significantly (P less than 0.05) lower body weight at 20 weeks of age than thep ulletsin the other pre-lay treatments. Feed consumption and feed efficiency were also adversely affected by this treatment, and sexual maturity was significantly (P less than 0.05) delayed. Early lay mortality from this treatment was evident. On the basis of egg production, egg weight, shell deformation and percent poorly shelled eggs (PSE) at point-of-lay, the pre-lay diets did not influence lay performance nor was there an interaction between any combination of pullet and lay diets. As the calcium levels of the lay diets increased, egg production, feed consumption and shell rigidity increased. The 1.5% calcium level did not maintain bone mineralization as compared to the 3.0 and 4.5% calcium levels. It was noted that shell quality on the basis of PSE and deformation does not begin to deteriorate immediately after the onset of production. In fact there is a short period of time where the egg shells improve and then there is a gradual decline in shell rigidity. The layers fed the lay diet containing 1.5% calcium produced eggs weighing an average of 57.4 g. This was significantly (P less than 0.05) lower than the eggs of the 2.3, 3.0 or 4.5% calcium fed groups which produced eggs weighing 59.1, 58.6 and 59.4 g. respectively.


Effect of extensive resection of small intestine on the enterochromaffin cells of the remaining intestinal segment. The authors discuss the problem of quantitative changes in enterochromaffin cells in the rat small intestine after its extensive resection. An increase was found in the number of these cells in the peripheral part of the intestine 4 to 8 weeks after the operation. These quantitative changes are explained by the regenerative activity in this period.


Efficacy of lyophilized turkey herpesvirus vaccine against Marek's disease in broilers. Field trials involving approximately 1,250,000 chickens vaccinated with cell-free turkey herpesvirus (HVT) vaccine and 635,000 chickens vaccinated with cell-associated HVT vaccine howed both vaccines equally effective in reducing condemnations (attributable to Marek's disease) at the poultry processing plant. Vaccinated chickens were progeny of hens vaccinated at 1 day of age with cell-associated HVT vaccine. The maternal antibody did not interfere with the ability of either the cell-free or cell-associated HVT vaccine to provide protection for chickens against challenge from the virulent Marek's disease virus.


Studies on the behavior of lymphocytes in the direct lymphocytotoxicity test (DLT) in surgical patients: II. Dynamics of immunological reactivity in selected cases. The results of investigations on the dynamics of immune reactivity are presented in 6 cases selected from 38 surgical patients. The investigations were carried out during surgical treatment of peripheral arterial diseases, malignant neoplasms of the alimentary tract, and extensive chronic inflammatory processes of the soft tissues. The evaluation of immune reactivity of these patients was based on the results of the direct lymphocytotoxicity test (DLT), the intensity of the autolymphocytotoxic reactions in the cold (15 degrees C) test, morphology and other changes of lymphocytes (various forms, lysis, leukergy) and on their ability to undergo blastic transformation in vitro after stimulation with PHA. The joint evaluation of investigations carried out repeatedly in these diseases may be useful for tracing the dynamics of immune reactivity in surgical patients.


The histology of cardiac blood clots in chicks exhibiting the "flip-over" syndrome. Chickens exhibiting "flip-over" syndrome were found on necropsy to have a blood structure in the heart chamber. Histological studies showed that this structure is formed of erythrocytes, leucocytes, fibrin and serum. Fibroblasts, collagen fibers, and thrombocyte agglutination were not observed. These observations indicate that the structures studied are post-mortem blood clots.


Cytochemical abnormalities of the leukocytes of peripheral blood of rabbits in chronic experimental intoxication with mercuric vapors. Cytochemical changes were studied in leukocytes in peripheral blood smears from rabbits chronically exposed to mercury vapor. Experimental animals were exposed in a toxicologic chamber to air containing metallic mercury in concentrations of 2.0-2.5 mg/m3 for 3 hours daily over 12 weeks. In the poisoned rabbits, as compared with controls, alkaline phosphatase activity was depressed in granulocytes, and lactate dehydrogenase activity in granulocytes and lymphocytes. The activities of acid phosphatase, arylsulphatase, 5'-nucleotidase, the color reaction with Sudan black B and the p.a.S. reaction were not affected.


Metabolizable energy (M.E.) values of three protein supplements as determined with chicks and laying hens. The M.E. values of three protein supplements that are produced and/or processed in Lebanon and Jordan were determined employing the method of Hill and Anderson (1958). Two experiments were conducted using broiler-type chicks in one experiment and White Leghorn laying hens in the other experiment. Nitrogen-corrected M.E. values expressed in kcal./kg. dry matter were found to be 2513, 2690 and 3215 for the soybean, sesame and poultry by-product meals, respectivel, as determined with chicks, and 2522, 2747 and 3155 as determined with laying hens. Hence, it was concluded that chicks were as efficient as laying hens in energy utilization of these protein supplements. For all practical purposes, it was recommended that metabolizable energy values, of commonly used protein supplements, determined with either chicks or laying hens could be used in poultry ration formulation.


Recurrent goiter.

Recurrent goiter. The authors report on 134 patients operated upon in the years 1950 through 1973 for recurrent goiter at the Department I of General Surgery, Institute of Surgery, Medical Academy in Poznań. The causes of recurrence, manifestations, indications for operation and the types of operations, postoperative complications and results of follow-up examinations are discussed.


Reproductive response to intermittent light regimens in Coturnix coturnix japonica. The effect of intermittent light regimens of one hour of light interspaced with dark periods of one, two or three hours, repeated three, four, five or six times per day was determined for age to first egg, hen day percent production and egg production for a 126 day experimental period in females, and the age to initial response of the cloacal gland in males. Three broad classes of response were noted based on the equivalent light period (ELP), which is defined as the interval from the beginning of the first intermittent light period to the end of the last intermittent light each 24 hour period, or the length of the single six and 14 hour light periods in the control groups. Group 1 was non-stimulated and had an ELP of less than or equal to 10 hours. There was an intermediately stimulated group with an ELP of 11 hours, and a stimulated group with an ELP of greater than or equal to 13 hours. The responses in males and females were parallel. Light intensity of either 460 lumens (average) or 2.6 lumens (average) intensity had little effect on the responses in females or males. Single, long duration exposures to light of less than or equal to 10 hours gave responses similar to intermittent regimens with ELP of less than or equal to 10 hours, while those with durations of 11 and 12 hours were intermediate and those of greater than or equal to 13 hours were equivalent to those with ELP of greater than or equal to 13 hours.


Energy needs of dwarf (dw) broiler breeder hens. Studies were conducted to determine the daily energy needs of the dwarf broiler breeder hen. In the first study, hens were control-fed diets ranging from 325 to 400 M.E. kcal./hen/day with ample amounts of other essential nutrients. Hens did not totally consume all of their daily allotment so in a second study the calorie allowance ranged from 260 to 320 M.E. kcal./hen/day. From the results of these studies it is estimated that the daily energy requirement of the dwarf broiler breeder hen is greater than 249 but no more than 269 M.E. kcal./day.


Effect of papain injection on mineral concentration in tissues of roosters and hens. A study was made of the effect of injected papain on the concentration of calcium, iron, copper, zinc and selenium in tissues of roosters and laying hens. Half the males and females were injected intravenously with a papain solution and the other half with 0.9% sodium chloride. The roosters and half the laying hens were injected one-hour ante-mortem and the others injected 24 hours ante-mortem. The laying hens had less Zn, Fe, Cu and Ca in the skeletal muscle than the roosters, and less Fe and Cu, but equivalent amounts of Ca and Zn, in the kidneys. In the roosters the kidney contained approximately five times as much Se as the muscle. The liver contained equivalent concentrations of Se in the roosters and laying hens. Papain had no effect on the concentration of any of the elements in the tissues. There was no significant difference in the concentration of the minerals between one-hour and 24-hour ante-mortem injections of the papain in the laying hens.


The anemia caused by aflatoxin.

The anemia caused by aflatoxin. The effects of graded doses of dietary aflatoxin (0, 0.625, 1.25, 2.5, 5.0, and 10.0 mug./g.) on hemoglobin, packed blood cell volume, erythrocyte count, leucocyte counts, bone marrow lipid, and bone marrow nucleic acids of chickens were measured. The hemoglobin, packed cell volume, and erythrocyte count were reduced significantly (P less than 0.05) to about the same extent by any given dose. Microscopic examination of stained smears of the bone marrow revealed a hyperplastic response including the granulocytic elements. Chemical analyses of the marrow revealed a decreased lipid content and an increased content of ribonucleic acid and deoxyribonucleic acid. Total leucocytes were increased about three fold by aflatoxin (10 mug./g). Differential leucocyte counts revealed that the heterophils were increased while the eosinophils were unaffected and the basophils, lymphocytes, and monocytes were decreased. The increase in nucleic acids of the marrow and in circulating leucocytes occurred with doses which inhibit growth rate. These data suggest that aflatoxin causes a hemolytic anemia in chickens, that aflatoxin, by itself, is not involved in the hemorrhagic anemia syndrome of chickens, and that aflatoxin does not cause in chickens a general inhibition of ribonucleic acid and protein synthesis as assumed from studies on rats.


Effect on reserpine on humoral immune responsiveness in young chickens. The role of reserpine in modifying a primary humoral immune response was evaluated in three experiments with young chickens. It was found that chickens injected with reserpine prior to an intravenous antigenic challenge with sheep red blood cells exhibited an enhanced primary humoral immune response. The enhanced response occurred concomitant with an elevation in adrenal cortical activity as evidenced by the significant elevation of serum corticosterone in the reserpine-treated chickens. These data suggest that both the adrenal cortex and medulla may influence immune responsiveness in the chicken.


The effect of level of feed intake on metabolizable energy values measured with adult roosters. Two experiments were made with S.C.W.L. roosters to test the hypothesis that the apparent M.E. value of a feedingstuff is affected by the level of intake. In the first experiment the birds were starved for 18 hr. and then fed varying amounts of whole wheat. Excreta voided during the 24 hr. experimental period was collected quantitatively and assayed for gross energy. Energy voided as excreta increased in a linear manner as the intake of wheat increased. The apparent M.E. value also varied with wheat consumption according to the equation M.E. (kcal./g.) = 3.17X - 8.5/X where: 3.17 kcal./g. is the true M.E. value of the wheat; 8.5 kcal. represents the sum of the metabolic fecal and endogenous urinary energy losses; and X is the weight of wheat consumed (g). A supplementary observation was that the metabolic fecal and endogenous nitrogen excretion of the roosters was 144 mg./kg./24 hr. In the second experiment corn oil was placed in the crops of starved roosters and the energy voided as excreta in 24 hr. was measured. The true M.E. value of the corn oil was 9.40 kcal./g. but the apparent value varied with intake. It is therefore concluded that the original hypothesis is correct. The findings of these experiments may explain some of the reported variations in M.E. data. A new approach to the assay for M.E. is proposed.


Effects of dietary aflatoxin on certain egg yolk parameters. Aflatoxicosis was induced in laying hens by incorporating graded amounts of aflatoxin into a commercial layer ration (0, 1.25, 2.5, 5.0, and 10.0 mug./g. of feed). After four weeks liver size and liver lipid were increased by aflatoxin while egg production and egg size were decreased (P less than 0.05). Total yolk weight and the yolk as percent of total egg weight were lowered (P less than 0.05). The dry weight and lipid content of the yolk were not affected. Yolk and plasma carotenoid concentrations were elevated (P less than 0.05). The data suggest that plasma and yolk lipids respond to the inhibition of lipid synthesis and transport from the liver by aflatoxin, but plasma and yolk carotenoids which are dietary in origin necessarily increase when egg production decreases during aflatoxicosis.


Production measurements affected by X-irradiation of chicken semen. Single Comb White Leghorn (S.C.W.L.) and Dark Cornish semen was X-irradiated with 1000 r. and introduced into S.C.W.L. hens to produce S.C.W.L. and crossbred chicks. The irradiation reduced the fertilizing capacity of the semen about 25 percent and the hatchability of the embryos about 38 percent. Semen of the two breeds was affected differently since there was much less alteration of embryonic development among purebred, S.C.W.L. chicks than among Cornish-sired crossbreds. As is typical, crossbred chicks gained weight faster than purebred S.C.W.L. irrespective of radiation damage. After irradiation, live weight was 4 percent less at 16 weeks of age for the crossbreds but no substantial effect on growth was evident for the S.C.W.L., although they were significantly heavier at hatching in the irradiated population. The rate of egg production in the first 30 days declined 15 percent under pressure from the irradiation damage. The distribution, as well as the frequency, of embryonic mortalities changed after parental semen irradiation. The majority of embryonic deaths occurred during the first 6 days of incubation with a coincidental decrease in the proportion of deaths occurring late during incubation. Posthatching mortalities were not affected for S.C.W.L. but were doubled for Cornish up to 16 weeks old.


Genetic differences in susceptibility to ulcerative enteritis in Japanese quail. Six lines of Japanese quail were derived from a single foundation population. Four of the lines were selected on the basis of family mean three week body weight, two were unselected and all lines were randomly mated. Quail were housed in wire batteries during the brooding, rearing and laying periods. During the brooding period, hover temperature and floor space per chick were similar from line to line. For the rearing and laying periods, floor space per chick was approximately the same from line to line. During an outbreak of ulcerative enteritis (diagnosed on the basis of gross and histopathology) in generation 31 and again in generation 34, mortality ranged from zero for males of one control line to approximately 50 percent for females of one selected  line. Analysis of variance showed that incidence of mortality differed significantly among lines and between sexes. Mortality was generally higher in selected than in control lines and in females than in males. It is suggested that susceptibility to ulcerative enteritis in quail may be a polygenically inherited trait and that the breeding which accompanied selection for body size may have made some loci homozygous for susceptibility alleles.


A rapid technique for the cleaning and concentration of Eimeria oocysts. A technique using 1% sodium bicarbonate, ether and centrifugation was developed for cleaning oocyts of Eimeria tenella, E. maxima or E. mivati. The speed and efficiency of this technique was compared with the sedimentation technique currently used in many laboratories. Parameters measured were percent sporulation after cleaning and number of oocysts recovered. Suspensions of oocysts cleaned by bicarbonate and ether consistently yielded a similar or superior percent sporulation. In four of the five trials bicarbonate and ether recovered a larger number of oocysts from feces. To determine the storage stability of oocysts cleaned with bicarbonate and ether in comparison with sedimentation cleaned oocysts, suspensions of Eimeria tenella and E. mivati were stored at 4 degrees C. and atssayed initially after harvest and a three month intervals thereafter. The parameters of bird weight gain, lesion score, mortality and feed conversion were measured to test viability of oocysts. Bicarbonate and ether cleaning had no initial deleterious effect on oocyst viability. After 6 months storage, oocysts of Eimeria cleaned with bicarbonate and ether maintained viability similar or superior to oocysts cleaned by sedimentation.