Tonic pupil: a simple screening test.

Tonic pupil: a simple screening test. The tonic pupil has a typical appearance and characteristic reactions to both light and the near reflex. Testing with Mecholyl (methacholine) is not possible since the drug is no longer manufactured. The reactions of a group of 25 patients with tonic pupil were studied using dilute pilocarpine, and compared with the pupil responses of a separate control group. We found that concentrations of 0.2% pilocarpine produced too many false-positive reactions in the control group and that 0.05% pilocarpine produced an insufficient response. The 0.1% concentration seemed suitable for ordinary clinical examinations and is recommended for pharmacologic confirmation of the diagnosis of tonic (Adie's) pupil.


Scanning electron microscopy of normal and lased rabbit retina. This study presents the topography as seen by scanning electron microscopy of the rabbit retina in general and the photoreceptors in particular; and of large laser lesions in the retina.


The use of bank sclera to correct lid retraction. Twenty-two scleral grafts were inserted in patients with retracted lids, the youngest patient was two years old at time of surgery. Two patients were operated on under local anaesthesia and the remainder under general anaesthesia. In the patients with thyroid disease larger grafts were required, the temporal side of the graft being 3 mm greater vertically than the nasal. Our first cases were undercorrected, so we used grafts of a size at least twice that required to lower the lid. Other complications were rare. For ptosis overcorrections, and congenital lid retraction, the graft should be 2 mm bigger horizontally and vertically than the amount required to lower the lid.


Lactic acid in human aqueous humour.

Lactic acid in human aqueous humour. We wished to assess the contribution of the lens to the maintenance of the high level of lactic acid found in human aqueous humour. The lactic acid in aqueous humour was estimated by Pryce's modification of the Barker-Summerson method in 41 subjects who were divided into four groups: those with early cataract, those with advanced nuclear cataract, those with mature cataract and those with hypermature (morgagnian type) cataract. Statistical evaluation of the results showed that there was no significant difference in the lactic acid level between the four groups. We assume that the lens does not contribute significantly to the high concentration of lactate found in human aqueous humour.


Monocular elevator paresis, Argyll Robertson pupils and sarcoidosis. A patient with sarcoidosis involving the central nervous system is described who developed monocular paralysis of elevation and Argyll Robertson pupils. A schema for the control system for vertical eye movements is presented as well as an explanation for monocular elevator palsy. The postulated lesion for monocular elevator palsy could well produce at the same time Argyll Robertson pupils and the cause of this papillary abnormality is discussed.


A 'black cornea' secondary to topical epinephrine. We report a case of 'black cornea" secondary to topical epinephrine therapy and present the biochemical analysis of the lesion. The formed pigment is a melanin and not the intermediate substance, adrenochrome, as has been previously reported. The pathogenesis of melanin deposition is reviewed and a hypothesis of epinephrine-melanin binding is suggested.


Lack of a significant protective effect of augmented circulating glucose on the ischemic myocardium.BJ. Infusion of glucose alone or glucose with insulin in cats subjected to acute myocardial ischemia did not alter the hemodynamic response of the cats to coronary artery ligation. Furthermore, determination of myocardial creatine phosphokinase (CPK) (ATP:creatine N-phosphotransferase, EC 2.7.3.2) activities failed to reveal a protective effect of glucose and insulin upon the status of the developing infarct in the ischemic myocardium. However, glucose and insulin apparently promote clearance of CPK from the plasma and inhibit proteolysis during the early phase of myocardial ischemia. These actions may be of value in generalized adaptive response of the animal to the stress of ischemia, but does not per se appear to diminish the spread of the ischemic damage within the heart not to limit the extension of the evolving infarct.


Induced rouleaux formation in interspecies populations of red cells. A study was made of rouleaux formation between erythrocytes of different species when suspended in Ringer solution with polyvinylpyrrolidone added (PVP with M.W 360 000, 4.0 G/L). PVP was shown previously to be a suitable asymmetric macromolecule for promoting rouleaux formation. For the present study fresh samples of blood were obtained from humans, cats, rats, mice, dogs, rabbits and guinea pigs. Initally homogenous populations of cells were allowed to form rouleaux in the microscope chamber for the purpose of determining the average cellular dimensions for each species. Subsequently red cells from two species at a time were mixed in equal proportions to assess the degree of preference for the cells of one species to form rouleaux among themselves rather than with cells of the other species. The sequencing of the cells in the mixed rouleaux which formed on the coverslip was determined from photomicrographs, using the previously determined knowledge of the cellular dimensions. Although the visual impression was that the rouleaux were composed of a random selection of cells from the mixed population, a preferencnstrated statisically in nine of the ten combinations tested. Only the rat-mouse mixture of cells was excepted, perhaps because these animals are closely related members of the same family.


Tonin activity in rat saliva: effect of sympathomimetic and parasympathomimetic drugs. The effects of carbachol, propranolol and isoproterenol on tonin concentrations in rat saliva have been investigated. The results suggest that the activity of this enzyme in rat saliva is dependent on activity of beta-adrenergic receptors.


The electrophysiological basis of the motor inhibitory effect of adrenaline on rabbit small intestinal smooth muscle. The spontaneous electrical activity of small intestinal smooth muscle cells consists of repetive depolarizations (control activity) on which spikes (response activity) may be superimposed; each spike is preceded by a prepotential. Response activity is associated with contractions. Adrenaline initially abolished the response activity and any prepotenials, as well as the contractions, without altering the control activity or the membrane potential. This effect was followed by hyperpolarization and slight increase in the control potential amplitude. The hyperpolarization was insenstitive tto temperature (Q10 = 1.01) and was larger when the membrane was initially depolarized by K withdrawal but did not occur after the membrane was hyperpolarized by replacing C1 by propionate or by prolonged K withdrawal. It is suggested that adrenaline inhibits intestinal motility by uncoupling the control activity to response activity through suppression of the prepotentials. The adrenaline-induced hyperpolarization may be due to an increase in K permeability but not to stimulation of electrogenic Na pumping. The increase in K permeability may depend upon the presence of Cl ions.


The effects of certain drugs on the uptake and release of [3H]noradrenaline in rat whole brain homogenates. Twelve drugs were studied with respect to their effects on inhbition of neuronal uptake of [3H]noradrenaline ([3H]NA) and on release of this amine from presynaptic nerve terminals. An in vitro method, using a crude synaptosomal homogenate prepared from rat whole brain, was employed. All drugs tested were found to produce some release of [3H]NA although tyramine was by far the most potent drug in this respect; tripelennamine and cocaine were observed to produce the least release. Studies of inhibition of NA uptake again demonstrated tyramine to be the most potent of the 12 drugs although in this case it did not differ significantly from cocaine and tripelennaine. The remaining compounds also showed decreased accumulation of [3H]NA and all 12 drugs produced uptake inhibition at a lower dose than that required for release of the amine. A correlation between releasing potency and lipophilicity of the compounds indicated that tyramine seemed to be acting in a different manner from the remaining compounds. A correlation between inhibitory potency and lipophilicity could be demonstrated for only six of the drugs, with tyramine, tripelennamine and cocaine showing the greatest deviation from this relationship.


Lack of effect of alcohol on small intestinal binding of the vitamin B12 - intrinsic factor complex. Absorption of 57Co-labelled vitamin B12 - intrinsic factor (IF) complex and its binding to mucosal precipitate and brush border fractions of rat small intestine was studied in rats pair-fed with a liquid diet containing ethanol 5 g/100 ml, 35% of calories, or isocalorically substituted sucrose. IF was obtained from rats fasted for 18 h. and for each experiment the amount of vitamin B12 added was the minimum required to achieve maximum binding to IF. Rats fed alcohol exhibited hepatic steatosis, proliferation of smooth endoplasmic reticulum, and disordered mitochondria after 6 weeks on the diet, and absorption of vitamin B12, fed with IF by stomach tube, was reduced signficantly. In contrast, binding of 57Co-labelled vitamin B12 -IF complex to mucosal precipitate and brush border fractions was never less than that of fractions from control rats at 4, 8 and 12 weeks on the alcohol diet. Furthermore, binding to the brush border was significantly greater in alcohol-fed rats at 12 weeks whether expressed per unit of beta-naphthylamidase (EC 3.4.1.1) activity or per milligram of protein. Total mucosal sucrase (EC 5.2.1.26) and beta-naphthylamidase were unchanged or slightly increased (beta-naphthylamidase at 12 weeks) on the alcohol-containing diet indicating that total brush border membrane was not reduced. Total brush border binding activity was the same in alcohol-fed and control rats at each time period. These results indicate that malabsorption of vitamin B12 in rats fed alcohol cannot be due to decreased binding of the vitamin B12 - IF complex by brush border membrane receptors, or secondary to a net decrease in membrane receptors.


Release of red cells from the slowly-exchanging splenic pool after noradrenaline administration. Isolated, denervated, cat spleens were perfused at constant flow with modified Ringer solution. Perfusion, pressure, outflow rate, and outflow red cell concentration were measured against time. After splenic perfusion by 500 ml solution the cell washout curve became a single exponential function, indicating that only cells from the most slowly exchanging red cell compartment remained (these are immature and abnormal cells which adhere to the fine structures of the red pulp). Splenic contraction was induced by injection of 5 mug noradrenaline into the inflow after perfusion by 600 and 1000 ml of fluid, respectively; outflow cell concentration rose 17-fold before returning to baseline value and 32% of red cells in the spleen were expelled. The time course of changes in cell concentration was similar in shape but delayed with respect to that of outflow rate. The transit time of the cells from the site of release to the splenic vein must have exceeded 40 s, which is consistent only with release from the red pulp. Furthermore, at the peak of the cell concentration curve the mean reticulocyte count was 37.8%. Thus immature and abnormal red cells, which comprise the slowly-exchanging compartment, are indeed released from the spleen during contraction.


Action potential fatigue in nonmyelinated nerve fibers: garfish olfactory and rabbit vagus nerve. A decrease in amplitude and conduction speed in the compound action potential is observed with time in gar olfactory and rabbit vagus nerve when it is stimulated between 4 and 15 Hz at 26 degrees C in vitro. The amplitude decays exponentially for 1-3 min before reaching a steady state. Recs 15 s for gar olfactory nerve and 50 s for rabbit vagus nerve. The steady state values are 14% and 36% of the original amplitude, respectively, and conduction speeds are reduced by 25 % in both nerves. The effect results from completion between ion flow during the action potential and active transport. The accumulation of K+ions and depletion of Na+ ions in the restricted extracellular space contributes to the amplitude fatigue while the depletion of Na+ ions alone causes the decrease in conduction speed. Ouabain increases the fatigue rate in both preparations, but more so for gar. The fatigue and recovery measurements may provide a useful method to investigate active pumping, including both the total pumping rate and the electrogenic component.


Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities. The effects of viloxazine, a clinically effective antidepressant, on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake and various related pharmacological activities were determined and compared to those of the tricyclic antidepressants desimipramine, imipramine, and amitriptyline. Viloxazine inhibitied [3H]NA uptake in the mouse and rat heart, being maximally about one half as potent as imipramine with a similar onset, but shorter duration of action than imipramine. The drug did not inhibit [3H]NA uptake in rat medulla or hypothalamus in contrast to desimipramine and imipramine, but it did alter [3H]NA metabolites in a similar manner. Viloxazine, like desimipramine, was a weak blocker of mouse brain 5-HT uptake, but differed from desimipramine as it poteniated 5-HT-mediated functions in the mouse and rat, as did imipramine and amitriptyline, the latter drugs being relatively potent blockers of 5-HT uptake. Viloxazine potentiated the L-DOPA behavioural syndrome in the mouse, antagonized reserpine-induced ptosis and hypothermia in the mouse, and inhibited gastric acid secretion in the rat, but was less potent than the tricyclic antidepressants. No appreciable in vivo inhibition of monoamine oxidase (EC 1.4.3.4.) activity in the mouse was exhibited. Like imipramine, the drug potentiated the ocular effects of L-adrenaline in the rabbit. It was similar to imipramine in potency in potentiating the apomorphine-induced gnawing in the mouse. The drug antagonized oxotremorine-induced hypothermia in the mouse but differed from the tricyclic antidepressants in not exhibiting the anticholinergic effects of blocking the tremors, salivation and lacrimation. Thus, viloxazine exhibits activities related to the biogenic amines both similar to and different from the tricyclics desimipramine, imipramine, and amitriptyline. These actions appear to be of relevance with respect to the antidepressant action of this drug.


The effect of taurine on calcium exchange of sarcoplasmic reticulum of guinea pig heart studied by means of dialysis kinetics. Calcium binding and release by sarcoplasmic reticulum vesicles of guinea pig heart were studied by means of a dialysis apparatus and analyzed with a model of three closed compartments. The rate constants of calcium binding were increased by taurine, and this effect was dose-related, whereas calcium efflux rate constants were very near to 0 in control experiments and were not effected by taurine. Taurine therefore increased the calcium content of sarcoplasmic vesicles and decreased the calcium concentration of the medium. beta-Alanine had no action on calcium fluxes.


A dual mechanism for the anticonvulsant action of aminooxyacetic acid. The intramuscular injection of aminooxyacetic acid (AOAA) into mice elevated the concentration of gamma-aminobutyric acid (GABA) in the brain, inhibited glutamic acid decarboxylase activity and delayed the onset of isonicotinic acid hydrazide induced seizures. Analyses of these results and of those obtained previously by the authors and other workers indicated that the anticonvulsant action of AOAA involved two mechanisms. One, involving GABA metabolism, was most effective 6 h after AOAA administration, and the other, not involving GABA, was maximally effective 1.5 h after AOAA injection and was completely absent after 6 h. Depending on the convulsant agent under study, the mechanism of the anticonvulsant action of AOAA was purely of the GABA type, purely of the non-GABA type or a combination of both types.


Toxicity testing in vitro. I. The effects of delta 9-tetrahydrocannabinol and aflatoxin B1 on the growth of cultured human fibroblasts. The acute toxicity of delta 9-tetrahydrocannabinol (delta 9-THC) and aflatoxin B1 to two strains of cultured human fibroblasts has been studied. delta 9-THC had no effect on cell plating efficiency or on the growth of mass cultures at doses of 1 mug/ml (3.18 muM) or less; at 10 mug/ml plating efficiency was reduced by approximately half and at 20 mug/ml colony formation was zero. Aflatoxin B1 reduced plating efficiency at dose levels of 0.1 mug/ml (0.32 muM) and above; in mass clultures it retarded growth at 1 mug/ml and produced complete inhibition at 5 mug/ml. The potential usefulness of cultured human fibroblasts in toxicity testing is discussed and the importance of using normal diploid cells rather than aneuploid permanent lines is emphasized. The limitations of cell cultures in assessing toxicity, and possible solutions to these are considered.


Toxicity testing in vitro. II. Use of a microsome - cultured human fibroblast system to study the cytotoxicity of cyclophosphamide. The toxicity of cyclophosphamide (CP), has been studied using a human fibroblast cell culture system. A method is described in which CP is incubated with liver microsomes and appropriate co-factors before addition to the cells. This permits activation of the CP to its cytotoxic metabolite but avoids the necessity of adding microsomes directly to the cell culture. It was demonstrated that under these conditions CP was irreversibly toxic to the cells within hours at dose levels larger than or equal to 0.3 mg/ml. In the absence of microsomal activation it was toxic at similar dose levels but the toxic effects required several days to develop.


Characterization of natriuretic activity from posterior pituitary lobes. Previous studies have indicated the existence of natriuretic factors of hormonal nature with the posterior pituitary gland as a possible site of origin. It was in this light that a series of experiments was designed to examine the posterior pituitary for such factors. Acetic acid extracts of porcine and bovine posterior pituitary lobe tissue were subjected to gel filtration on Sephadex G-25. Several fractions in the molecular size range of 1000 were obtained which possessed potent natriuretic activity as assayed in rats. The activity of these fractions maximally increased sodium excretion to 6-8 muequiv./min, a 10- to 40-fold increase above control, when administered intraperitoneally to hydropenic, conscious rats. However, oxytocin and vasopressin, present in the posterior pituitary are natriuretic. These hormones were measured by radioimmunoassay, and invariably only those fractions which contained vasopressin and (or) oxytocin possessed natriuretic activity. Moreover, the extent of the natriuresis could be accounted for by the vasopressin and (or) oxytocin content of the test fractions. The natriuretic property of this material was abolished by treatment with thioglycollate. Further purification of natriuretic fractions by ion exchange resins, thin-layer chromatography and isoelectric focusing failed to resolve natriuretic activity from vasopressin and oxytocin. Similar results were observed following analysis of fractions isolated by gel filtration of acetic acid extracts of ventral hypothalamus tissue. The natriuretic fractions isolated from hypothalamic tissue were indistinguishable from oxytocin and vasopressin. These experiments suggest that the natriuretic activity in neurohypophyseal extracts can be attributed to oxytocin and vasopressin.


Nonparticipation of adrenergic mechanism in potassium-induced relaxation of taenia from guinea pig caecum. In the isolated taenia caeci of guinea pigs excess potassium (10-30 mM) induced a phasic relaxation followed by a contraction. This phasic relaxation was unaffected by treatment with  hexamethonium, phentolamine, propranolol and bretylium. However, relaxation induced by perivascular nerve stimulation was inhibited by all these agents but not by hexamethonium. Tetrodotoxin inhibited both forms of relaxation. Potassium-induced relaxation was not accompanied by [3H]noradrenaline release. Perivascular nerve stimulation caused release of [3H]noradrenaline and this was blocked by bretylium. Treatment with ouabain or replacement of NaCl by LiCl, but not treatment by cold storage, inhibited the potassium-induced relaxation. These results suggest that the potassium-induced relaxation of taenia caeci was due to electrogenic sodium pumping and was independent of the adrenergic innervation of the tissue.


The thyroidal response to chronic goitrogenic stimulation and the persistence of effects of early goitrogenic stimulation. The effects of overstimulation of the thyroid gland induced by the feeding or rapeseed meal or thiouracil during the growing period persisted for as long as 75 weeks after withdrawal of the source of goitrogen from the diet. Thyroid weight, thyroid iodine content and radioiodine uptake were all increased in birds which had received goitrogen during the growing period. Follicle diameter was greater and the height of epithelial cells was lower than in control birds. The thyroid changes in these birds were deduced to be compensatory because production characteristics were normal and distribution of a dose of radioiodine into thyronines (T3 + T4) was similar in the birds which had received goitrogen during the growing period and in the control birds. Birds which were being fed rapeseed meal at the time the thyroid gland were examined showed effects which varied in magnitude according to the length of time over which rapeseed meal had been fed. Thyroid weight, follicle diameter, amount of epithelial tissue present and the total amount of iodine in the thyroid glands increased, whereas coupling efficiency (radioiodine-labelled T3 + T4)/(monoiodotyrosine/diiodotyrosine) declined with time.


Pituitary response to auditory stress: effect of treatment with alpha-methyl-p-tyrosine. Usefulness of a factorial mixed design for statistical analysis. Eight adult male rats were chronically cannulated in the jugular vein and placed individually in a sound-attenuated cubicle. Four of the animals were also implanted with a permanent cannula in the right lateral ventricle of the brain. Each animal was submitted twice to auditory stress at a 24-h interval. Before each stress, the rats were pretreated with either saline or alpha-methyl-p-tyrosine (alpha-MT), the order of administration of the drug and its vehicle being alternated in the eight rats. The injections were made either intravenously or intraventricularly. Auditory stress significantly depressed plasma growth hormone (GH) levels irrespective of the type of pretreatment. Mean plasma GH levels were significantly lower after alpha-MT pretreatment. alpha-MT pretreated animals had higher mean plasma corticosterone (B) levels which remained unchanged during stress. Plasma follicle stimulating hormone (FSH) levels were not modified by stress nor by alpha-MT pretreatment. The intraventricular administration of alpha-MT at a dose (20 mg/kg) which is ineffective by a systemic route produced the same effects on GH and B levels as the intravenous injection (250 mg/kg). These data seem to indicate that auditory stress exerts its inhibitory effect on GH secretion through a noncatecholaminergic pathway. They show, on the other hand, the existence of a central catecholaminergic tonus, stimulatory for GH and inhibitory for B. Statistical analysis was based on a factorial mixed design for repeated measurements after logarithmic transformation of the data. The purpose, advantages and limits of this procedure are presented and discussed.


The effects of oral diazepam pretreatment on the biliary excretion of sulfobromophthalein in rats. Studies were performed with rats to examine the effects of single, as well as repetitive oral diazepam (DZP) pretreatment on biliary sulfobromophthalein (BSP) excretion rates and on bile flow parameters. One-hour pretreatment of male rats with 150 mg/kg of DZP resulted in about a one-third reduction in the peak biliary excretion rate of BSP (60 mg/kg, iv) and this was associated with a decrease in relative proportions of conjugated BSP in bile. The biliary excretion of preconjugated BSP was unaffected. BSP hepatic uptake and storage were apparently unaffected. In vitro DZP markedly inhibited BSP conjugating activity. In contrast to the above results, when BSP excretion was examined 1 h after the last of five daily oral doses of DZP (150 mg kg-1 day-1), no change in the peak elimination rate of this dye was evident. However, bile flow rates were higher in DZP-treated rats than in controls. When rats were examined 24 h after the last of five daily oral doses of DZP (150 mg/kg), the choleretic response persisted. Further studies showed that the repetitive DZP pretreatment enhanced the bile salt-independent mechanisms of bile formation.


Inotropic and chronotropic responses of the in vivo denervated dog myocardium to dobutamine. The inotropic and chronotropic responses to dobutamine (DBA) and isoprenaline (5ISO) were examined in eight chloralose anaesthetised dogs. Following acute cardiac denervation, heart rate (HR) and contractility (dP/dtmax), measured at a fixed paced atrial rate, were recorded during intravenous infusion of incremental doses of DBA and ISO. Both DBA and ISO elicited increases in HR and dP/dtmax. The increases in dP/dtmax for a one beat per minute increase in HR was 102.0 +/- 10.6 mm Hg/s (1 mm Hg (0 degree C) = 133.322 Pa), during DBA infusion, and 61.5 +/- 8.4 mm Hg/s during ISO infusion. It appeared that the relatively greater inotropic effect of DBA in comparison with ISO was the result of an augmentation of its inotropic activity. DBA infusion was accompanied by a significant increase in mean aortic pressure at all doses examined. An increase in afterload may account for part of the increased inotropic responses to DBA.


Interaction of propranolol and phentolamine with ethanol in the rat. The possible role of the adrenergic nervous system in the intoxicant effects of ethanol was examined in studies of the interaction or propranolol and phentolamine with ethanol. Propranolol teneded to increase the effect of lower doses of ethanol in a dose-dependent manner. However, the effect of higher doses of ethanol (over 2.0 g/kg) tended to be diminished by low doses of propranolol, whereas higher doses of propranolol were ineffective or actually increased the ethanol effect. Phentolamine tended to decrease the effect of the lower ethanol doses. These findings are inconsistent with any simple adrenergic mechanism in the mediation of the intoxicant effect of ethanol.


The relaxant effect of adenosine-5'-alpha, beta-methylenediphosphonate on the longitudinal smooth muscle of the rabbit ileum. The response pattern of the isolated longitudinal muscle of the rabbit ileum to adenosine-5'-alpha, beta-methylenediphosphonate (APCP) was found to differ from that caused by adenosine or ATP in that the rapid initial phase of relaxation is absent and that at doses above 10 muM a secondary increase of contractile activity occurs in the continued presence of the nucleotide. This secondary phase was attenuated after indomethacin pretreatment and reestablishement of tone with acetylcholine. Theophylline did not modify APCP-induced relaxations while effectively antagonizing those caused by adenosine. It appears that APCP acts via a receptor site or pathway distinct from that of adenosine or ATP.


Differing estrogenic activities for the enantiomers of o, p'-DDT in immature female rats. Female rats (20-21 days) were given single intraperitoneal injections of (+/-)-o,p'-DDT, (--)-o,p'-DDT, or (+)-o,p'-DDT. At 18 h their uteri were excised and the estrogen sensitive parameters, uterine wet weight, and uterine glycogen content were measured. For o,p'-DDT, the levo enantiomer is the more active estrogen in immature female rats. Optical resolutions of other racemic environmental xenobiotics may be important in the evaluation of their biological effects.


Extracellular nuclease produced by a marine bacterium. I. Extracellular deoxyribonuclease formation by a marine Vibrio sp. Deoxyribonuclease (DNase) activity was found in the culture fluids of numerous marine bacteria isolated from seawater. Among these ogranisms, marine bacterium, Vibrio sp., strain No. 2, showed the highest deoxyribonucleic acid-hydrolyzing activity. This organism requires salts of seawater for both growth and extracellular DNase formation. The DNase activity could not be detected in the synthetic seawater culture liquid lacking magnesium ion, and DNase activity decreased in a calcium-deficient medium. The optimum temperature for the growth of this organism was between 15 and 25 degrees C. The formation of extracellular DNase was the greatest at 20 degrees C and less activity was found at 10 and 30 degrees C.


Macrophage function and host resistance against infection with Toxoplasma gondii. The role of macrophages on the course of an infection with Toxoplasma gondii has been examined. Stimulation of macrophage function by killed Bordetella pertussis cells did not show any beneficial effect as an increased susceptibility became apparent. The functional blockade of macrophages by dextran sulfate or carbon particles did not result in a higher susceptibility of mice to the lethal primary infection with T. gondii. Thus in vivo macrophages apparently do not play an essential role as effector cells as they do in infections with other obligate intracellular infective organisms such as Listeria monocytogenes. The spleen is apparently of crucial importance for resistance against T. gondii infection, since death occurred earlier in splenectomized mice than in control animals.


Isolation and characterization of nocardia-like variants of Mycobacterium smegmatis. Orange-red-pigmented (OR) colonies were isolated from cream-yellow-pigmented Mycobacterium smegmatis after exposure to either mycobacteriophage MC4 or ultraviolet light; these variant strains were designated OR4 and ORuv, respectively. Early subculture of OR-colonies did not show any segregation of parental-type cells. However, colonies resembling the parental strains, possibly representing a back mutant (REV-OR4), were occasionally found during subculture of established OR-colonies or upon treatment with N-nitrose-N'-nitro-N-methylguanidine. The OR-variants were characterized by their lytic response to nocardiophage, but not to mycobacteriophages, presence of alpha-branched, beta-hydroxylated fatty acids of the Nocardia-type, and a guanine plus cytosine value of deoxyribonucleic acid (DNA) between 62 and 64 mol%. They were more resistant to the lethal action of both ultraviolet light and mitomycin C treatment than the parental and back mutant strains. Although the OR-variants in this study possess characteristics common to the genus Nocardia or some of the 'rhodochrous' mycobacteria, evidence is presented that they form a new class of mycobacterial variants.


The effects of glucosamine derivatives on the growth of cultivable Treponema. The effects of glucosamine and its derivatives on the growth of Treponema phagedenis biotypes reiter and kazan 5 were studied to determine if these agents could act as growth stimulants for organisms of the genus Treptonema. Growth studies on the cultivable treponemes were conducted in culture tubes containing glucosamine, glucosamine derivatives, and (or) glucose and galactose in serum-based media. Glucosamine and N-phenylacetylglucosamine were definitely inhibitory to growth at the concentrations studied. N-acetylglucosamine (NAG) produced mixed effects.


Investigations of nitrogenase activity in rheotrophic peat. Acetylene reduction by the peat microflora was unaffected by light, but was sensitive to temperature, with an optimum of about 30 degrees C. The nitrogenase was inactivated by exposure to temperatures above about 35 degrees C. Activity occurred in completely anaerobic conditions; the rate of ethylene production was of the order of 0.5 nmol C2H4 ml-1 h-1. Experiments with time courses indicated that exposure to oxygen caused an initial inhibition of activity followed by a period in which ethylene production was stimulated to rates much higher than in the anaerobic tests; both the inhibition and stimulation appeared to be related to the level of oxygenation. It is suggested that these results could be explained by the existence of nitrogen-fixing associations of aerobic and anaerobic bacteria in the peat. The stimulation of activity caused by exposure to air indicates that care must be taken when interpreting results of the assay obtained from waterlogged organic soils.


Effect of magnesium and some nutrients on the growth and nuclease formation of a moderate halophile, Micrococcus varians var. halophilus. Production of halophilic nuclease by a moderate halophile, Micrococcus varians, ATCC 21971, was maximal at 2.5 to 3.5 M NaCl concentration in a complex medium (CM) composed of 1% casamino acids, 1% yeast extract, and NaCl. The addition of 81 mM MgSO4 to CM inhibited nuclease production in spite of good growth. Microscopic observation showed that this inhibition was accompanied by complete clumping of the cells. The Sehgal and Gibbons complex medium (SGC) which contained 0.75% vitamin-free casamino acids, 1% yeast extract, and NaCl, however, supported good production of the nuclease in spite of the presence of 81 mM MgSO4. It seemed that both magnesium sulfate and some substances present in CM might be responsible for this inhibition and clumping. A synthetic medium optimal for enzyme production was developed consisting of 16 amino acids, 4 vitamins, 0.73 mM KH2PO4, 2.7 mM KCl, 20 mM MgSO4, and 2.5 M NaCl. The organism required biotin as an essential growth factor, and thiamine, riboflavin, and choline as stimulating factors. Omission of isoleucine from the medium reduced markedly the growth rate. Glutamic acid, proline, and arginine were consumed completely during cultivation in the synthetic medium.


Adsorption of Pseudomonas pseudomallei cytophilic antibodies onto rabbit alveolar macrophages. Cytophilic antibody has been demonstrated in sera from rabbits immunized with Pseudomonas pseudomallei. This antibody passively adsorbed onto normal rabbit alveolar macrophages rendered the macrophages agglutinable by P. pseudomalei antigens and capable of displaying 'rosette' formation with polysaccharide-sensitized erythrocytes.


Stability of mRNA from the Clostridium sporogenes phage F1. Polyacrylamide gel electrophoresis was used to study the decay of individual species of mRNA in F1, a bacteriophage specific for the obligate anaerobie Clostridium sporogenes. Immediate early mRNA species had a half-life of 3.5 min, while delayed early and late mRNA had a half-life of between 6 and 8 min.


Physical characteristics of DNA from bacteriophages of Agrobacterium tumefaciens. DNA was extracted from isolates of bacteriophages grown on virulent and avirulent strains of Agrobacterium tumefaciens. Molecular weights of DNA from phages isolated from the virulent A. tumefaciens (IIBV7) were about 41.5 X 10(6) daltons, while those from the avirulent A. tumefaciens (IIBNV6) were about 32.5 X 10(6) daltons. The buoyant densities of the four DNA's ranged from 1.7086 to 1.7089 g/cm3, values that were not significantly different. DNA-DNA hybridization studies also indicated that the four phages were closely related. Attempts to induce tumors with phage DNA were unsuccessful.


Antibacterial activity of marine violet-pigmented Alteromonas with special reference to the production of brominated compounds. The synthesis of several types of antibiotics was investigated in four strains of violet-pigmented bacteria belonging to the species Alteromonas luteo-violaceus. Two of the strains simultaneously produce an antibiotic polyanionic polysaccharide, weakly bound to the cells and diffusing throughout the medium, and two intracellular brominated bactericidal substances. The third strain only synthesizes the polyanionic antibiotic. The fourth one is totally inactive. The macromolecular antibiotic, probably responsible for the autointoxication of the bacteria in their cultures, acts at the respiratory level; it induces an increase of oxygen uptake and the production of peroxides by test bacteria. Thus, its activity is inhibited by catalase and peroxidase.


Suitability of membrane-filter techniques to study the ultrastructure of Fusarium solani in soil. The suitability of two types of membrane filters for scanning and transmission electron-microscopical examination of chlamydospores formed from macroconidia of Fusarium solani from soil was tested. An improved method to incubate propagules in soil and to collect them free from soil particles for electron-microscopical observations is described. Best results were obtained if macroconidia were incubated in soil between two Nucleopore membrane filters. Both chlamydospore morphology and lysis, however, were affected to some extent in comparison with that on single membranes. This is probably due to a selective effect on the microflora colonizing the chlamydospores.


Ultrastructure of forming and dormant chlamydospores of Fusarium solani in soil. Chlamydospores of Fusarium solani f. sp. cucurbitae, F. solani f. sp. phaseoli and F. solani f. sp. pisi formed in soil were recovered at intervals and examined by electron microscopy. Cell wall material outside the newly formed chlamydospore cell wall gradually disintegrated. Protoplasts of chlamydospore cells lyse without prior penetration of the cell wall by microorganisms. The mechanisms of lysis of chlamydospores of F. solani in soil are discussed.


The isolation of an infectious A protein--RNA complex from coliphage R17. The coprecipitate of A protein and RNA which results from acetic acid treatment of bacteriophage R17 has been shown to form two bands after equilibrium density gradient centrifugation in Cs2SO4. The band of higher density, whose position coincides with that of phage RNA prepared by phenolisation possesses neither A protein nor infectivity while the band of lower density which contains both RNA and A protein is infectious for intact E. coli cells. The nature of the bonding between the A protein and the RNA was also investigated.


[Degradation of hydrocarbons in the presence of other organic substances by bacteria isolated from seawater]. Three bacterial strains, isolated on gas-oil from seawater, have a variously changed growth on hexadecane with supply of two organic substances. Acetate reduces growth of all tested strains and particularly the hexadecane degradation by Acinetobacter sp. On the contrary, trypticase-phytone promotes the degradation by the three strains.


Potash guar gum--a source of halophilic bacteria. Moderate and extreme halophilic microorganisms have been isolated from guar gum solutions dissolved in potash brine for use in sylvite froth flotation. Tentative identifications have been made of vibrio, Halobacterium, and Halococcus species. Reinoculation of these isolates into guar gum solutions has shown that they are not carbohydrate-utilizing strains, but instead metabolize the contaminating proteins present in guar.


In situ morphologies of deep-sea and sediment bacteria. Deep-sea and sediment bacteria at the bottom of an approximately 1200-m water column were sampled by means of pressure vessels attached to a remote underwater manipulator. Cells were immediately fixed in situ with glutaraldehyde, and after processing in the laboratory their morphologies were observed with the scanning electron microscope. Most bacteria were coccoid or rod-lide and less than 0.4 mum in diameter or width. Few filamentous bacteria were observed. Bacteria were in aggregates or free-living. It is concluded that morphologies of deep-sea bacteria collected and fixed at the hydrostatic pressure of their environment are, in general, similar to the observed morphologies of deep-sea bacteria determined at 1 atm pressure after collection and decompression during ascent through the water column.


The occurrence of cell-associated enterotoxin B in Staphylococcus aureus. Cell-associated enterotoxin B was detected in lysates of cells of Staphylococcus aureus S-6 and 4916 disrupted by sonication or lysostaphin treatment. As much as 67% of this total cell-associated toxin was surface-bound, located outside the cytoplasmic membrane, and was released during protoplasting of this organism by lysostaphin treatment in hypertonic medium. The remainder of the cell-associated toxin was termed cytoplasmic and was released during osmotic lysis of the protoplasts. Levels of cell-associated toxin as a function of the age of the cells showed a rapid increase in both surface-bound, cytoplasmic, and total cell-associated toxin levels during the period of active toxin synthesis (late exponential phase of growth). These cell-associated toxin levels then reached a peak as the culture entered stationary phase, at a time corresponding to a decrease in the rate of toxin synthesis, and decreased slowly thereafter.


Procedures for obtaining sectional views of fungal fructifications by scanning electron microscopy. Procedures for sectioning fungal fructifications in host tissues or on artificial media are described, which allow observation of internal structures by scanning electron microscopy. Perithecia of Ceratocystis fimbriata and Phyllachora graminis, and telia of Puccinia xanthii showed excellent preservation of exposed structures in sections which were osmium-coated before being dried. While similar preservation was obtained in sectioned acervuli of Lecanosticta acicola and Marssonia juglandis and in pycnidia of Dothiorella ribis and Phomopsis occulta, the mucilaginous substances produced in these fructifications precluded observation of conidiophores. Extraction of mucilage from these sections was accomplished by periodic acid and dilute KOH treatments, followed by an osmium-coating procedure. In such preparations, mucilage was removed, internal structures were preserved, and pertinent characteristics of conidiogenous cells were resolved.


Sparing effect of lithium ion on the specific requirement for sodium ion for growth of Vibrio parahaemolyticus. The role of NaCl in the growth of Vibrio parahaemolyticus strain A-55 was investigated. Maximal growth was obtained at 0.5 M NaCl in a synthetic medium. Na+ could not be replaced for growth by any other cations or substances. When the medium was kept isotonic with 0.5 M NaCl by the addition of sucrose, good growth was obtained with 0.1 M NaCl. By reducing the osmotic pressure and decreasing the NaCl concentration from 0.5 M to 0.1 M, the same growth yield was obtained as when using a medium containing 0.02 M NaCl and 0.08 M LiCl. This was not the case with sucrose. Therefore, it is concluded that ionic strength and osmotic pressure are important environmental factors affecting growth. The minimal essential requirement for Na+ for growth of V. parahaemolyticus was 0.003 M, because this was never replaced with any other cations and agents. Hence, requirement for Na+ for growth involves a specific requirement for Na+, ionic strength, and osmotic pressure, respective concentrations being 0.003 M, 0.047 M, and 0.45 M. Osmotic support was required for growth when the concentration of NaCl was decreased to 0.05 M. The effect of ionic strength of monovalent cations other than Na+ on growth was examined at 0.003 M NaCl. Among LiCl, NH4Cl, KCl, and RbCl, Li+ was the most accelerative for growth in the synthetic medium.


Bacteriorhodopsin formation in Halobacterium halobium. Systematic examinations were made of factors influencing bacteriorhodopsin formation during the growth of Halobacterium halobium. Light-induced adenosine triphosphate (ATP) production and [14C]proline uptake were used as measures of functional ability of the purple membrane. Maximum bacteriorhodopsin formation occurred under growth conditions of illumination and limited aeration. The purple membrane -ATP production system did not confer an appreciable growth advantage. Growth in the dark or with adequate aeration partially suppressed bacteriorhodopsin formation and the effects were additive. Nicotine effectively inhibited bacteriorhodopsin formation. A rapid synthesis of functional pigment occurred when washed suspensions of cells which had been grown under illumination with nicotine present were incubated under dark, aerobic conditions. The alleviation of this nicotine inhibition was not blocked by chloramphenicol or bacitracin. Bacteriorhodopsin formation was negligible when washed suspensions of cells from dark, limited aeration or light, adequate aeration cultures were incubated in the light with limited aeration. A nutritionally complex medium was needed to elicit appreciable bacteriorhodopsin formation by the cells from the dark or adequately aerated cultures. Bacitracin partially inhibited this bacteriorhodopsin formation by cells form the light, adequately aerated culture.


Deoxyribonucleic acid studies in the genus Caryophanon. The deoxyribonucleic acid (DNA) of 36 isolates of Caryophanon latum and 3 isolates designated Caryophanon tenue, obtained from geographically diverse regions, has been examined for guanine plus cytosine (mol % G+C) base composition, genome size, and for relative reassociation levels. The isolates were found to be homogenous and group-specific in their base composition, with C. latum DNA ranging from 44.0 to 45.6 mol % G+C, and C. tenue from 41.2 to 41.6 mol % G+C. Genome size determined for representative isolates confirmed the distinction of the two groups. The genome size ranged from 1100 to 1200 X 10(6) daltons for C. latum and from 900 to 1000 X 10(6) daltons for C. tenue. DNA:DNA hybridization studies revealed relative reassociation levels as follows: C. latum to C. latum, 78-94%, C. tenue to C. tenue, 82-94%; and C. latum to C. tenue, 13-30%. Finally, based on genome size and mol % G+C similarities, DNA:DNA hybridization experiments between two strains of Lactobacillus and C. latum and C. tenue were performed. These experiments revealed essentially no polynucleotide sequence similarity between the Lactobacillus and Caryophanon isolates used.


Respiration rates for determining the effects of urea on the soil-surface organic horizon of a black spruce stand. The respiration rates of microflora of layers of soil-surface organic horizon of a black spruce (Picea mariana (Mill.) B.S.P.) stand have been studied manometrically under controlled conditions of moisture, temperature, and aeration in the presence of urea and other nitrogen and mineral amendments. L.F., and F2 samples from field plots fertilized with 448 kg N/ha as urea in 1961 had still in 1971 greater respiration rates than similar samples from unfertilized field plots. In lab tests, addition of urea (112, 280, and 448 kg N/ha or 875, 2187, and 3500 ppm N) stimulated the endogenous respiration of each layer. The stimulation was greater when 2187 ppm N was applied and when moisture and temperature of the layers were maintained at 60% water-holding capacity and 20 degrees C during the 42-day incubation period. Addition of Mg, Ca, and K to urea-fertilized layers increased respiration while P and S decreased it. Addition of NH4NO3 and (NH4)2SO4 impaired the endogenous respiration. The endogenous respiration and moisture, temperature, and fertilizer effects decreased in the order L,F1, and F2 layers.


Bouyant density, conversion formulae, and the mole percent guanosine + cytosine content of Desulfovibrio sp. A reevaluation of the original buoyant density conversion formula used to calculate the molar percentage guanosine + cytosine (% G + C) contents of the accepted species of genus Desulfovibrio has been undertaken. It would appear that the formula used gives values 4-5% lower than those obtained using formulae more generally cited in modern literature. Recalculations of % G + C content values for Lesulfovibrio DNA are presented using the formulae of three different workers, and are compared with those values originally used in the classification of genus Desulfovibrio.


Water-soluble contrast radiculography of the lumbar region. Water-soluble contrast radiculography has been used for many years. Earlier contrast media were highly irritant and subjects required preliminary spinal anesthesia but, recently, better-tolerated contrast media such as meglumine iocarmate (Dimer X) and metrizamide (Amipaque) have been used. The findings from 300 examinations with meglumine iocarmate are presented. Methodology is discussed. The diagnostic accuracy of this contrast medium was high and side effects were minimal. Comment is made on the newest spinal contrast medium--metrizamide--and its use in 29 examinations in Canada.


Endoscopic retrograde cholangiopancreatography in the management of pancreatic and biliary disease. Endoscopic retrograde cholangiopancreatography is a new and valuable technique in the diagnosis of jaundice, pancreatic disease and obscure upper abdominal pain. Endoscopic sphincterotomy of the sphincter of Oddi and the extraction of stones from the common bile duct are an extension of this procedure already in use in several high-volume centres. Cannulation of the bile ducts and pancreatic ducts in tests of secretion and cytology will become increasingly common applications of the technique. In order to provide dependability and cost-effectiveness, specialists in this procedure must maintain a high volume, necessarily limiting it to a few practitioners. Use of a trained endoscopic technician, a radiologist trained in endoscopy, or an endoscopist trained in fluoroscopy and spot-filming may decrease the manpower costs of this procedure.


Acute pancreatitis occurring in heterotopic pancreatic tissue in the gallbladder. A 54-year-old man with acute upper abdominal pain was found to have pancreatic heterotopia in the wall of the gallbladder. The aberrant pancreatic tissue and the gallbladder wall were the sites of acute inflammation and of fat necrosis. Pancreatic heterotopia of the gallbladder is extremely rare; only 10 proven cases have been reported previously. The most common sites are the stomach, duodenum and jejunum.


Perforated peptic ulcer in pregnancy with survival of mother and child: case report and review of the literature. Peptic ulcer in pregnancy and its complications, though rare, can be life-threatening to mother and fetus. Perforated peptic ulcer in pregnancy is extremely rare; when this occurs survival of both mother and child is unusual. Only five cases of maternal survival following perforation of a peptic ulcer have previously been recorded and, of these, only three were associated with survival of both mother and infant. The authors report an additional case of perforated ulcer in pregnancy with survival of mother and infant, and review the relevant literature. Early surgical diagnosis and treatment followed by vaginal delivery of the fetus offers the best hope for survival of mother and child.


Immunologic response in vitro after thymechtomy in patients with myasthenia gravis. Thymectomy in adult animals impairs immune functions such as lymphocyte response to phytohemagglutinin (PHA) and to allogeneic cells. The responses of lymphocytes from 18 myasthenia gravis patients, 12 of whom had undergone thymectomy, were studied; the interval between thymectomy and investigation ranged from 1 month to 26 years (mean, 9.5 years). Peripheral blood lymphocytes were cultured in autochthonous plasma or homologous AB serum. In vitro responses to stimulation with PHA, concanavalin A and allogeneic monomuclear cells were within the 95% range of normal responses in all patients. Because our findings contrast with the definite immune defects resulting from thymectomy found in adult animals, longer follow-up is needed.


Hyperactives as young adults: preliminary report. Thirty-five individuals aged 17 to 24 in whom severe chronic hyperactivity had been diagnosed 10 years before were studied together with 25 matched controls. There were no significant differences in mean height or weight or in electroencephalographic findings, but the mean pulse rate was significantly higher in the hyperactive group. Cognitive style tests indicated continued difficulty in reflection (resulting in more errors) but less impulsivity (longer reaction time) in the hyperactive individuals. Compared with controls, hyperactive subjects were continuing to have more scholastic difficulty, although this difference seemed to be less pronounced than 5 years before. Their adjustment in work situations and living arrangements did not differ significantly from that of the controls. Restlessness, both reported and observed, continued to be a problem for the hyperactive individuals, and socialization skills and sense of well-being continued to be poorer than in the controls. The hyperactive individuals did not show significantly more antisocial behaviour, nonmedical use of drugs or serious psychiatric disturbances.


Stabilometry as a diagnostic tool in clinical medicine. Stabilomety, a method of measuring stability of stance or postural equilibrium in man, consists of transforming the mechanical oscillations of man's "physiologic gravicentre" into electric signals, then amplifying, recording and analysing the signals. The frequency, duration and mean and maximum amplitudes of oscillations, and coefficients reflecting the influence of vision, differ in patients with various neurologic diseases and from values in healthy subjects. The method is highly sensitive and accurate, simple and rapid to use, lacks danger and discomfort and permits screening of a large number of people in a short time.


Management of the patient requiring leg amputation for peripheral vascular disease. Most leg amputations are performed because of the effects of peripheral vascular disease. Only 50% of such amputations were performed below the knee in Ontario in 1972, although the knee joint should be preserved in most patients. Careful preoperative evaluation is essential. Postoperative problems include gas gangrene for which prophylactic measures are recommended; failure of the stump to heal, which necessitates early revision of the stump; and defects in stump contour, which necessitate late revision. An enthusiastic team approach to rehabilitation is necessary to overcome the physical and mental problems that result from amputation of a leg.


Mobile hearing program in central rural Manitoba. A mobile hearing program was developed to detect and alleviate deafness and rehabilitate deaf individuals in rural Manitoba. The first project was established in central Manitoba in December 1973 for children, whose school performance can be affected by minimal hearing loss. Volunteers from the community, trained by an audiologist, conduct screening procedures, and children with possible hearing impairment receive audiologic and otolaryngologic assessment. Close clinical liaison between audiologist and otologist is important.


Marfan syndrome with coronary artery lesions in a North American Indian. Marfan syndrome has not been well documented in North American Indians. A 19-year old Ojibwa man had evidence of this syndrome -- specifically, tall stature, long, thin extremities (particularly, fingers and toes), increased urinary excretion of hydroxyproline, aortic aneurysm, aortic regurgitation and pathologic evidence of aortic rupture and alastic tissue fragmentation. Intimal hyperplasia was present in the extramural coronary arteries, while the intramural arteries, usually thought to be involved, were normal.


Carrier detection and genetic counselling in Duchenne muscular dystrophy: a follow-up study. Assay of serum creatine kinase activity is useful in the detection of carriers of the X-linked gene for Duchenne muscular dystrophy (DMD). For genetic counselling this assay has been used in conjunction with pedigree analysis to improve estimates of the risk that a female relative of a DMD patient is a carrier. To measure the impact of the program, follow-up information was obtained from women who had received genetic counselling for DMD. Their responses showed that the risk of producing an affected son had been a major factor in their attitude toward family planning, and their reproductive performance correlated inversely with their genetic risk. The decision by the majority of proven carriers to prevent the birth of further male offspring was reflected in a recent decline in the frequency of a known family history of DMD among newly ascertained cases.


Lithium iodide cardiac pacemakers: initial clinical experience. A new long-life cardiac pacemaker pulse generator powered by a lithium iodide fuel cell was introduced in Canada in 1973. The compact, hermetically sealed unit is easily implanted and reliable, has excellent patient acceptance and has an anticipated battery life of almost 14 years. Among 105 patients who received a lithium iodide pacemaker, complications occurred in 18. The lithium iodide pacemaker represents a significant advance in pacemaker generator technology and is recommended for long-term cardiac pacing; the manufacturer guarantees the pulse generator for 6 years.


Pellagra.

Pellagra. Pellagra due to malnutrition occurred in an Ottawa women in 1973. She was given a normal diet with supplements of riboflavin, thiamine, niacin and ascorbic acid. The clinical response was striking. Although pellagra is still common in some parts of the world, it is now rare in North America. The disease may occur secondary to malnutrition or malabsorption; inborn errors of metabolism or transport, as in Hartnup disease; deviation of precursors of niacin, as in carcinoid syndrome; or competitive inhibition of niacin incorporation into nicotinamide-adenine dinucleotide, as with administration of isoniazid.


Familial aggregation of blood pressure in 558 adopted children. Blood pressure was measured in each member of 398 French-Canadian families with at least one adopted child of the same ethnic origin. Measurements were made at home by a nurse, usually with the subject seated. One comparison per family between parents and randomly chosen index children was made, using age- and sex-adjusted scores. The correlation in blood pressure scores between parents and natural children was highly significant (P less than 0.001), at 10.2% for systolic and 13.7% for diastolic in 140 homes with at least one natural child, but the correlation between parents and adopted children was nonsignificant, at 0.81% and 1.0%, in 398 homes with at least one adopted child. The correlation between pairs of natural children was significant (P less than 0.05), at 7.84% for systolic and 8.41% for diastolic, in 80 homes with more than one natural child but nonsignificant, at 0.49% and 1.69%, respectively, for pairs of adopted children in 138 families with more than one adopted child. It is concluded that heredity explains most of the familial resemblance of blood pressure in children.


The Nutrition Canada Survey: a review. Statement by the Nutrition Committee of the Canadian Paediatric Society. The data obtained through the Nutrition Canada national nutrition survey must be interpreted cautiously because of limitations in both the design of the survey and our present knowledge of the implications of the findings. The data suggest that, at present, nutritional status is suboptimal among members of the general population. However, because there is no evidence of clinically apparent malnutrition it is difficult to judge the immediate health significance of this finding. Among the Inuit, however, the data suggest that intake of vitamin C may be sufficiently low to approach the level causing clinical problems. Government should make funds available to permit analysis of the data to be completed and investigative studies to be undertaken to assess the health significance of the findings.


Mebendazole in the treatment of helminthiasis. Mebendazole, a new broad-spectrum anthelmintic, was used to treat patients with nematode infections--ascariasis, trichuriasis and hookworm. The dosage for adults was 100 mg twice daily for 3 days and for children, 50 mg twice daily for 3 days. Pretreatment and post-treatment egg counts on stool specimens showed that after mebendazole there was a reduction of over 99% in egg count per gram of stool in all three types of infection. The overall cure rates for the infections were as follows: Ascaris lumbricoides, 86.8% (59/68); Trichuris trichiura, 86.0% (37/43); and hookworm, 85.7% (24/28). The drug was equally effective in light and heavy infections. No important side effect was noted with this drug. It is suggested that mebendazole is the drug of choice for trichuriasis and mixed nematode infection.


Ten-year results of the treatment of primary operable breast carcinoma: A summary of 304 patients evaluated by the TNM system. After all records of patients with breast cancer who received primary treatment at Memorial Hospital in 1960 were reviewed, 304 women with operable, infiltrating carcinoma were identified and classified clinically according to the TNM system of the American Joint Committee for Cancer Staging and End Results Reporting. There were 66 patients (22%) classified under Stage I, 176 (58%) under Stage II, and 62 (20%) under Stage III. There were 82 patients (27%) in whom the nodal status was misclassified clinically. The observed 10-year survival was 59.7%. The 10-year end results (with 95% confidence limits) diminished significantly in relation to advancing clinical stage of disease--90.9% (+/-6.9%) for Stage I, 57.1% (+/-7.3%) for Stage II, and 33.9% (+/-11.8%) for Stage III patients. The 10-year survival in patients with pathologically negative axillary nodes was 71.5%, and in the patients with pathologically positive axillary nodes, 48.3%.


Should curative surgery be attempted in patients with cancer of the main stem bronchus? Among tumors of the lung, main stem bronchial cancer offers a particularly unfavorable prognosis, probably because of its rapid extension to the segmental bronchi, trachea, and extrapulmonary structures. However, analysis of data gathered by the End Results Group indicates that survival among those patients with main stem bronchial cancer whose tumor was resected was virtually the same as that of patients with resectable lung cancer of other sites. From these data it is impossible to assess what role, if any, the resection itself played, and a randomized trial would be necessary to determine whether resection improves the probability of patient survival. On the other hand, it is not now advisable to deny resection to patients with operable main stem bronchial tumors (except oat cell tumors) on the basis of the available nonexperimental evidence alone.


Microinvasive carcinoma of the uterine cervix: A long-term followup study of eighty cases. One hundred and eleven patients with microinvasive carcinoma of the uterine cervix were studied over a 21-year period. Thirty-five cases of carcinoma in situ with questionable stromal invasion were excluded. Cases with pathologic examination of less than a cervical cone or the entire cervix were not accepted. The sole pathologic criterion for inclusion was unequivocal invasion to a depth of no more than 5.0 mm. Ninety-one patients were followed for 5 years or until death, and 80 patients for 10 years or until death. One patient was lost to follow-up at 5.5 years. The two deaths officially attributed to cervix cancer prior to 10 years were signed out by nonphysician assistant coroners. Available clinical evidence indicates that at least one of these patients, and probably both, did not die of cervix cancer. From these data, simple hysterectomy would seem to be the maximal treatment indicated. Since the prognosis of microinvasive carcinoma is similar to that of carcinoma in situ, it is suggested that such cases not be included when considering the end results of Stage I cervix cancer.


Phase I studies with Baker's Antifol (BAF) (NSC 139105). Phase I studies were conducted in 58 adult cancer patients with Baker's Antifol (BAF), a new active-site directed inhibitor of dihydrofolate reductase. Dose escalation ranged from 10 to 250 mg/m2/day X 5 days and courses of treatment were repeated every 2-3 weeks. Biologic effects were observed mostly at doses greater than 100 mg/m2/day X 5 days. The patients developed myelosuppression during 19% of the trials. Other types of toxicity were dermatitis in 12 to 30% and stomatitis in 7 to 38% of the trials. Toxicity was directly related to the impairment of the patient's liver function. Two partial responses (in a patient with adenocarcinoma of the lung and a patient with transitional cell carcinoma of the bladder) occurred. BAF is an active new chemotherapeutic agent which deserves further clinical trials in patients with various malignancies.


Relationship of glycolytic enzyme activities and response of breast cancer patients to chemotherapy: A preliminary report. Activities of glucosephosphate isomerase, lactate dehydrogenase, and NADP-isocitrate dehydrogenase were significantly elevated in breast cancer specimens from patients who responded favorably to combination cytotoxic chemotherapy regimens compared with those in carcinomas from patients failing to respond to the same chemotherapy. Presence of estrogen receptors and clinical response to hormonal therapy were also evaluated in neoplasms from these patients. The data suggest that measurement of the enzyme profile, along with estrogen receptor levels, may be useful in selecting a mode of therapy for patients with advanced disease.


Urinary-bladder toxicity following pelvic irradiation and simultaneous cyclophosphamide therapy. The frequency and severity of urinary-bladder toxicity were determined retrospectively in a large series of childhood cancer patients treated with either pelvic irradiation and simultaneous cyclophosphamide or cylclophosphamide with extrapelvic irradiation. Of 50 patients who received the first combination, 17 (34%) developed urinary-bladder toxicity. Eight of the 17 had transient hematuria and dysuria with complete clearing clinically after cessation of treatment; nine had chronic or intermittent hematuria which persisted after treatment was stopped and often resulted in demonstrable fibrosis and telangiectasia of the bladder. By contrast, of 60 children who received cyclophosphamide and radiotherapy outside the pelvic region, only five (8%) developed hematuria and in all instances it was transient. This comparative study demonstrates a significantly increased frequency and severity of urinary-bladder toxicity in cancer patients receiving pelvic irradiation with simultaneous cyclophosphamide.


Gastric epithelioid leiomyoma and leiomyosarcoma (leiomyoblastoma). A series of 127 surgical specimens of epithelioid leiomyomatous tumors (leiomyoblastomas) of the gastric wall from the files of the Armed Forces Institute of Pathology (AFIP) were studied as to biologic behavior, morphogenesis, and histologic features of value in distinguishing benign and malignant variants. These tumors affect middle-aged men primarily and usually present with upper gastrointestinal bleeding or peptic ulcer-like symptoms. They are composed of a mixture of round epithelioid and spindle cells, many of which have clear cytoplasm. The cells are ensheathed by delicate reticular fibers. The presence of a perithelial or glomoid pattern in some tumors suggests a possible relationship to angiomyoma, glomus tumors, and "pericytoma." The epithelioid leiomyoma, the benign form, often arises in the mid- and distal stomach, especially on the anterior wall. Microscopically, it is recognized by the presence of large epithelioid cells and infrequent mitotic figures. Of 103 epithelioid leiomyomas, only one metastasized and thus was biologically malignant. The epithelioid leiomyosarcoma often arises in the proximal stomach and also distally, especially on the posterior wall. Two histologic types of epithelioid leiomyosarcoma are distinguished from the benign epithelioid leiomyoma by the small size of the cells and occasional higher mitotic counts. One sarcoma variant is a small cell caricature of the leiomyoma. The other is more anaplastic, assoicated with a loss of reticular fibers surrounding the cells and an alveolar arrangement. Epithelioid leiomyosarcomas are the most common type of gastric sarcoma. They are aggressive neoplasms; 63% metastasized, usually within 2 years after diagnosis.


Infantile fibrosarcoma.

Infantile fibrosarcoma. The pathologic features and the behavior of 53 cases of infantile fibrosarcoma are presented. The tumor nearly always occurred during the first 2 years of life; 41 of the 53 cases occurred during the first, six during the second, and three each during the third and fourth year of life, respectively. Twenty of the 53 cases were present at birth. The tumor was more common in boys (60%) and affected chiefly the distal portions of the lower and upper extremities (72%). Most of the tumors grew rapidly and reached a large size within a few weeks or months. They were generally poorly circumscribed and infiltrated variously subcutaneous fat, muscle, fascia and tendons. Microscopically, they were composed of immature-appearing spindle-shaped cells and were marked by their high cellularity and prominent mitotic activity. Despite these features, follow-up information revealed a favorable clinical course, particularly as compared with the adult form of fibrosarcoma. Of the 48 patients with follow-up data, 31 were alive and well with no evidence of recurrence, eight were alive with recurrence, and one was alive following lobectomy for metastatic tumor. Of the living patients, 12 were treated with amputation, nine with radical or wide local excision, and 15 with simple excision. In two cases surgery was followed by chemotherapy, and in one, by radiotherapy. Eight of the 48 patients with follow-up had died, four of metastatic tumor (8.3%) and four of miscellaneous causes. Wide local excision appears to be the treatment of choice unless the size of the tumor and its anatomic location require amputation. Since late recurrent and metastatic lesions were encountered, long-term followup is necessary before one can safely assume that the patient has been cured.


The chromosomes and causation of human cancer and leukemia. XIX. Common markers in various tumors. Most human cancers are associated with abnormal (marker) chromosomes. In past and present studies banding analysis have uncovered a much larger number of markers in cancer cells than was seen with standard (Giemsa) staining. Furthermore, common markers of identical morphology and origin were found in tumors of related or unrelated tissues or organs, suggesting that in all probability such markers, although present in cancers of diverse nature, may indicate a common etiology, either related to the causation of the cancers, to the progression of the tumors, or to the predilection of certain chromosomes to undergo morphologic changes leading to marker formation. Even though some markers were common to different tumors, the bulk of the markers in the cancers studied could not be identified with certainty and their nature varied from tumor to tumor.


Pigmented squamous cell carcinoma of cornea and conjunctiva: A light microscopic, histochemical, and ultrastructural study. A light microscopic, histochemical, and ultrastructural study was performed on tissue obtained from a pigmented squamous cell carcinoma of the cornea and conjunctiva. To the best of our knowledge this is the first time that one of these rare pigmented squamous cell carcinomas of the ocular mucous membrane has been described in detail. The occurrence of this neoplasm, which needs to be differentiated from other pigmented lesions, and particularly epibulbar melanomas, underscores the fact that all pigmented tumors are not melanomas. The study revealed that melanin granules, which accounted for the pigmentation of the neoplasm, were present in variable numbers in neoplastic squamous cells, Langerhans cells, macrophages, and stellate cells identified as melanocytes with mature melanosomes. Premelanosomes were not observed in any of these cells types. Current concepts concerning the common association of Langerhans cells with their characteristic intracytoplasmic "Birbeck granules" and melanocytes are discussed.


Pulmonary blastoma: A light and electron microscopic study. A case of pulmonary blastoma studied with the electron microscope showed two distinct cell types, i.e., epithelial and mesenchymal elements. The former demonstrates the differentiation toward ciliated bronchial cells, and the latter, cartilage. In view of these findings, coupled with the current understanding of pulmonary morphogenesis, the pulmonary blastoma is more likely to be a carcinosarcoma than a true blastoma. However, the separation between pulmonary blastoma as usually employed and the so-called pulmonary carcinosarcoma seems to be desirable because of different clinicopathologic features.


Ultrastructural characteristics of sinus histiocytic reaction in lymph nodes draining various stages of breast cancer. An ultrastructural study of sinus histiocytosis (SH) in axillary lymph nodes was undertaken in 20 patients with primary cancer of the breast. The lymph node responses were first classified by means of light microscopy, according to previously established criteria. The ultrastructural findings established three major patterns of SH response in cancer-draining lymph nodes: developing SH, positive SH, and degenerative SH. These patterns followed closely the classification obtained by light microscopy. An important finding of electron microscopy was the presence of early activation of histiocytes (developing SH) in microscopy (negative SH). The striking ultrastructural resemblance of histiocytes in positive SH to epithelioid cells seen in delayed hypersensitivity reactions (TB) again points to the fact that the positive SH pattern represents a tumor-host reaction of the delayed hypersensitivity type. Finally, although the presence of virus has been shown to play a role in spontaneous BALB/c murine breast tumor, no virions could be found in human cancer-draining lymph nodes.


Blastomatous tumors of the respiratory tract. Two cases of blastomatous tumors of the respiratory tract are presented. The first is a pulmonary blastoma of an 81-year-old man, diagnosed as adenocarcinoma by cytologic examination, the cells being exfoliated from the large carcinomatous component. The patient died 1 year after manifestation of the symptoms. The second case is a tumor that developed in the nasopharynx of a 62-year-old man. This is the first reported case of a nasopharyngeal blastoma that presented a histology comparable to that seen in the pulmonary tumor. The presence of a hamartomatous benign mesenchymal component raises histogenetic considerations as to whether this was an independent part of an otherwise malignant tumor or whether it was induced by the malignant growth. Following incomplete surgical treatment and postoperative radiation, no recurrence was observed during the next 8 months.


Structure of psammoma bodies of a meningioma in scanning electron microscopy. Psammoma bodies in a human transitional meningioma were studied by scanning electron microscopy (SEM) of deparaffinized tissue slices and sections. The bodies, visible as round structures by light microscopy, were confirmed in SEM to have a spherical rather than tubular three-dimensional structure. They were distinctly demarcated from a surrounding cup-like wall of cells. Under high magnification, the undulating surface of the bodies was found to be covered by interwoven fibers. In cross-section the bodies had a lamellar internal structure. The lamellae consisted of a network of concentric strands and fibers with associated bead-like material. The structure of psammoma bodies seen in SEM speaks in favor of their genesis by calcification of concentrically deposited fibrillar extracellular material.


Acinic cell tumor of the bronchus.

Acinic cell tumor of the bronchus. A bronchogenic tumor was removed from a 12-year-old girl. Histology showed a clear cell lesion with electron microscope features compatible with serous acinic cell origin.


Erythrokinetics and androgens in bone marrow cancer. Erythrokinetic studies were conducted in 60 patients with chronic anemia due to bone marrow involvement by cancer and other diseases. Fifty-seven percent had evidence of ineffective erythropoiesis contributing to the severity of their anemia. Enhanced bone marrow activity in the extremities was detected in 14% of patients. Maximal doses of several oral androgens were given to 31 patients for at least 3 months. Only 26% of the patients increased their red cell mass by at least 20%. All who benefitted had a minimum level of effective erythropoiesis and showed a decline in serum iron concentration at least 30 mug/100 ml after 1 month of treatment. Erythropoietin values were not helpful in identifying responding patients. These findings indicated the value of erythrokinetic studies in defining the bone marrow capacity of patients with cancer who are considered for androgen treatment trials.


Lymphomatoid granulomatosis: A clinicopathologic study of four cases. Four cases of lymphomatoid granulomatosis were studied. One case, previously reported, has had a prolonged remission of 8 years' duration. In one case, the course was rapid and progressive, and the patient died 2 months after the onset of the disease. In two other patients, the disease appears to be arrested effectively, both clinically and radiographically, by administration of corticosteroids. In the fatal case, postmortem examination revealed a typical angiocentric and destructive polymorphous lymphoreticular infiltrate in the lungs, kidneys, and adrenal glands. The diagnosis was made on specimens obtained from three patients by open thoracotomy. An adequate specimen is mandatory for diagnosis and thoractomy is indicated. To be considered in the differential diagnosis are Wegener's granulomatosis, the limited form of Wegener's granulomatosis, lymphoma, allergic granulomatosis, lymphocytic interstitial pneumonia, plasma cell granuloma, and infectious granuloma.


Pathophysiology of hypoalbuminemia associated with carcinoid tumor. Decreased serum albumin levels are commonly observed in patients with carcinoid tumor, who also show several characteristic clinical and biochemical abnormalities. A large comparative study on a group of 96 carcinoid patients was performed with the purpose of identifying some of the mechanisms leading to hypoalbuminemia in patients with this form of cancer, and thereby to shed light on the cause of hypoalbuminemia of cancer in general. Serum albumin values were compared with a number of clinical parameters (including extent of liver metastases, severity of diarrhea, degree of right heart failure, and extent of gastrointestinal surgery) and of laboratory data (prothrombin time, BSP retention, serum transferrin concentration, hematocrit value, and daily urine excretion of 5-hydroxy-indoleacetic acid). In several patients the gastrointestinal protein loss was assessed by the 51Cr-albumin technique, whereas albumin renewal and distribution were evaluated by the use of 125I-albumin. The data obtained showed that the main factors in determining decreased serum albumin levels in patients with carcinoids are both reduced synthesis and increased loss of the protein. The hepatic synthetic defect appears to be related to a progressive decrease in the number of functioning liver cells; the origin of the gastrointestinal protein loss may be related to the obvious tumor involvement of the gut wall, as well as to the pharmacologically-induced diarrhea. Right heart failure occurring as a result of the carcinoid heart disease may be an additional cause for gastrointestinal protein loss in patients with carcinoid tumor.


A demonstration of androgen and estrogen receptors in a human breast cancer using a new protamine sulfate assay. Separate receptors for estrogen and androgen are demonstrated in cells from metastic human breast cancer. By criteria of binding affinity, number of binding sites, and specificity of the receptor for different steroids, the receptors are shown to be distinguishable. The protamine sulfate receptor assay technique employed allows both kinds of receptor to be quantified conveniently and reproducibly without interference by plasma steroid-binding components.


Tumors of fibrous tissue origin in childhood. A clinicopathologic study of cutaneous and soft tissue neoplasms in 66 children. Fibroblastic lesions in children present difficulties in diagnosis and in a justifiable therapeutic approach. This series reviews the clinical and pathologic features of fibroblastic soft tissue lesions from 66 children. Although radical procedures were occasionally required to achieve local control of an aggressive lesion, conservative surgery was generally successful. Recurrences were frequent, but only one lesion, in an adolescent, metastasized. No prognostic value could be found in anatomic location or in histologic features. Even cellular lesions with frequent mitoses ordinarily did not require the aggressive therapy needed in similar lesions in adults. In this series, incomplete original excision was frequent and usually related to the infiltrating margins of the lesion.


Proximal tubular adenomas of kidney with so-called oncocytic features. A clinicopathologic study of 13 cases of a rarely reported neoplasm. Four renal "oncocytomas" were observed between July 1974 and January 1975 at University Hospital. A review of all renal cell neoplasms previously classified as carcinomas since 1952 was conducted to determine whether this cluster of tumors represented a recent increase in incidence or whether other renal "oncocytomas" had gone unrecognized in the past. The 23-year review of 194 carcinomas yielded an additional nine "oncocytomas." None had appeared prior to 1964, whereas almost half were found in the 1973-1975 interval alone. While it appears that some "oncocytomas" of the kidney have gone unrecognized in the past, it is also evident that their recent increased incidence is epidemiologically significant. Renal "oncocytomas" and renal cell carcinomas are compared with respect to morphology, clinical presentation, and biologic behavior. Evidence derived from this comparison permits the conclusion that these neoplasms originate from proximal tubular epithelium, are benign clinicopathologic entities, and henceforth should be called proximal tubular adenomas with so-called "oncocytic" features.


Diffuse cystic glandular malformation of the stomach associated with adenocarcinoma: Case report and review of the literature. A 60-year-old man was found to have diffuse cystic glandular malformation and adenocarcinoma of the stomach. Review of the literature revealed one similar reported case and five others with diffuse heterotopic cystic malformation only. Clinically, the lesion is associated with gastrointestinal symptoms, and radiologically, it can mimic diffuse gastric carcinoma, lymphoma, and polyposis.


Tumor imaging in children.

Tumor imaging in children. Twnty-six children suspected of having malignant diseases were examined by Gallium-67 scintigraphy. The scintigrams were pathologic in the 20 children with final diagnoses of malignancy. The lesions visualized by scintigraphy were 12 primary tumors and eight cases of local recurrence or dissemination of cancer. Gallium-67 did not accumulate in a hematoma of the liver, and scintigraphy was normal in five children with no clinical evidence of tumor recurrence. Several cases are reported and the clinical value of 67Ca scintigraphy for detection and control of childhood neoplasms is emphasized.


Bilateral breast carcinomas: Role of mammography. From 1963 to 1973, at Emory Clinic, out of a total of 1112 patients with breast carcinoma studied with mammography, 83 had carcinoma in both breasts. The carcinoma in the second breast was primary in 67 patients and metastatic in 16 patients; in 18 patients there were simultaneous bilateral primary carcinomas. Mammography proved highly effective in detecting the second carcinoma and was reliable in differentiating a second primary from metastatic carcinoma. Forty-one of the second primary carcinomas were not associated with a palpable mass; 31 of these were having mammography as a routine check-up. The second nonsimultaneous carcinoma was considerably smaller than the first and fewer axillary lymph node metastasis. The second primary occurred within 6 years of the first in 86% of the cases with the remaining 14% scattered evenly up to 23 years. At 4 years after the diagnosis of the second primary, 25 of 27 deaths had occurred and only 1 patient was alive with cancer. Breast cancer patients need close follow-up for at least 6 years after the first primary carcinoma; and 4 years past the second primary signals a more optimistic prognosis.


Primary extramedullary esophageal plasmacytoma: First case report. Solitary extramedullary plasmacytomas are rare tumors, reported to occur most commonly in the upper respiratory passages, but which also are rarely seen in the middle and lower gastrointestinal system. This report documents the first primary plasmacytoma of the esophagus. A 67-year-old Caucasian man complained of dysphagia and weight loss. Preoperative diagnosis, based on functional inquiry, radiology, and biopsy, was undifferentiated carcinoma involving the lower third of esophagus. The patient was treated by esophagogastrectomy. The pathology specimen revealed the typical histology of plasmacytoma. The extramedullary nature of the tumor was established postoperatively on the basis of the following criteria: 1) Absence of Bence-Jones proteinurea; 2) normal serum electrophoresis; 3) normal bone marrow biopsy; and 4) absence of distant metastases on liver scan and bone survey.


Diagnostic scalene node biopsy in the preoperative evaluation of the surgical cancer patient: Five-year experience with 108 cases and literature review. Records were reviewed of 108 consecutive patients with a variety of surgically approachable malignancies undergoing scalene node biopsy as part of a preoperative staging evaluation. Metastases to the scalene nodes were detected in 12 patients (11.1%). In six patients the scalene nodes were clinically suspicious before biopsy, but in six with nonpalpable nodes the scalene metastases were occult clinically. Four of the patients with clinically benign, but pathologically positive, scalene biopsies were found among the group of 62 patients with epidermoid carcinoma of the cervix. It was concluded that routine scalene biopsies are justified in the properative evaluation of cancer patients only if the nodes are clinically suspicious, except for in patients with advanced pelvic cancers, in whom the incidence of completely occult scalene metastases is 6% or more.


Abdominoperineal resection: Treatment of choice for carcinoma of the rectum. Abdominoperineal resection cure adenocarcinoma of the rectum was performed in 62 patients between 1965 and 1969 at the Winnipeg General Hospital. Mean age was 64, ranging from 41 to 83; 40 patients were male and 22 female. Distribution by Dukes' staging was: A, 11; B, 28; C, 23. Complications occurred in 22 patients (35%). Average hospital stay was 29 days, 27 days in uncomplicated patients and 36 days in those with complications. There were two deaths, a 3.2% operative mortality rate. Sixty of the 62 patients were available for 5-year followup. Crude survival rate was 52%: A, 91%; B, 59%; C, 25%. Two patients died of an operation that permanently cured three patients in whom disease had spread beyond local confines. Abdominoperineal resection offered a 52% 5-year survival rate, increased the rate of cures in the unstaged patient by at least 5% over that afforded by local therapy, gave a 14% chance of cure in stage C disease compared with 0% with local therapy, and, compared with local therapy, was at least 67% more likely to offer cure than to kill in the event of disease spread to regional lymph nodes.


The long-term course of carcinoma in situ of the uterine cervix. The malignant potential of carcinoma in situ (CIS) of the uterine cervix has been the subject of great controversy. Despite refinements and additions to knowledge in this area, few reports on the long-term course of the disease have appeared in the past decade. Recent developments in diagnostic and therapeutic techniques coupled with changes in the patient population with this disease have prompted renewed interest in conservative management. Results of long-term observation of a group of patients followed initially without ablative therapy are reported. The data indicate that CIS of the uterine cervix is not the inevitably progressive disease that it has been considered to be. Unequivocal invasive cancer develops in only a small percentage of cases and can be controlled, if not cured, by current therapeutic modalities. The intraepithelial lesion, however, tends to persist despite conization, and eventually requires ablative therapy in most cases. Conservative procedures should be regarded as temporizing, at least until their long-term benefits can be recorded.


Normal pregnancy and delivery after cerebral metastases of choriocarcinoma: Case report. Normal pregnancy and delivery after chemotherapy and radiation of cerebral metastases in a case of choriocarcinoma is presented. The need of surgical approach to these lesions as proposed by Stilp and his group is questioned.


Five-year remissions of metastatic solid teratoma of the ovary. To date, only three 5-year survivors with metastatic solid malignant teratoma of the ovary have been reported. The authors report two additional cases surviving 5 years or greater. In both cases, the embryonal teratomatous elements matured to Grade 0 peritoneal metastases after intensive chemotherapy and surgery with or without radiotherapy. Since only one of the two patients had an objective response to therapy, we speculated that the maturation of the tumor in both patients might be, but is not proven to be, a consequence of chemotherapy, surgery, and/or radiotherapy. Because the prognosis, even in Stage IA solid ovarian teratoma, is so poor, we suggest that all such patients should have 2 years of adjuvant chemotherapy consisting of vincristine, dactinomycin, and cyclophosphamide. Patients with demonstrable metastases should receive the same chemotherapy until either all tumor has regressed or all immature elements have reverted to mature tissue.


Dental management of patients irradiated for oral cancer. Management of patients irradiated for oral cancer should include consideration of their oral health prior to, and after, radiation therapy. Data from 130 patients, followed for a period of 1 to 10 years, are presented and evaluated. The philosophy of retention and maintenance of as many teeth as possible is supported by this data. Extraction of teeth with severe periodontal disease after irradiation also proves to be a relatively safe operation. Osteoradionecrosis tends to be limited in extent and is generally well tolerated by the patient when treated conservatively. A treatment regimen is presented that significantly reduces the morbidity from therapeutic irradiation of the jaws. A comprehensive dental evaluation and follow-up plan coupled with patient cooperation are instrumental to the success of this program.


Postulated developmental forms in the life cycle of the lymphocystis virus. Electron micrographs of lymphocystis sk8n lesions obtained from the walleye pike, Stizostedion vitreum, show viral particles of differing sizes and morphologies. Earlier studies have described only particles ranging in size from 200-250 mmu in diameter. We show, in addition, new forms (65-100 mmu in diameter) intermingled among the large particles and also contained within the latter. Both forms are associated with a single inclusion body. The possible role of the small particle in the life cycle of the virus is discussed.


Comparison of the effects of nitrogen mustard on the functional properties of mitochondria from sensitive and resistant strains of Ehrlich ascites tumors. In vivo treatment of sensitive tumor cells with nitrogen mustard (HN2) results in marked inhibitions of protein and nucleic acid synthesis by mitochondria subsequently isolated from these cells. This inhibition occurs at doses of drug which produce no apparent inhibition of total RNA synthesis. The inhibition gradually reverses itself in sensitive cells and is less severe and more rapidly reversed in resistant cells. The in vivo sensitivity of the mitochondria is in striking contrast to their in vitro behavior; isolated mitochondria resist 50 times the in vivo ID50 level of the drug. The sensitivity of protein and RNA synthesis in mitochondria is presumed to be related to the differences in organization between the nucleocytoplasmic processes and the mitochondrial. But the data also suggest that the in vivo effects on mitochondria are indirect, either acting via the cytoplasm or nucleus or via a carrier mechanism having mitochondrial affinity.


Gangliosides and other lipids of hyperplastic liver nodules induced by N-2-fluorenylacetamide. Hyperplastic liver nodules induced in rats fed the carcinogen N-2-fluorenylacetamide had levels of total, protein-bound, and ganglioside sialic acid above those of controls. Yet, the total lipid content of hyperplastic nodules and surrounding tissue was nearly identical to the lipid content of control liver. Hyperplastic nodules and surrounding liver did not differ from control tissue in phospholipid distribution patterns or in fatty acid composition of total lipids, neutral lipids, and/or polar lipids. Elevated levels of both free and esterified sterols, and a slightly lower level of phospholipid, were found in both hyperplastic nodules and in surrounding tissue as compared to control liver. The increased sterol ester content was largely due to increased amounts of cholesterol oleate. Thin-layer chromatography of ganglioside extracts revealed all gangliosides of control liver. Amounts of tri- and tetrasialoganglioside were reduced and levels of disialoganglioside were increased in modules relative to both control liver and surrounding tissue. The ganglioside alterations may represent at least one significant minimal deviation of hyperplastic nodules toward the malignant phenotype in keeping with the hypothesis that hyperplastic nodules represent a pre malignant form of hyperplasia.


Combination chemotherapy in vitro with adriamycin. Observations of additive, antagonistic, and synergistic effects when used in two-drug combinations on cultured human lymphoma cells. Adriamycin was paired with 12 other chemotherapeutic drugs in a search for possible synergistic pairs. Cell lethality was investigated by the colony-formation method utilizing a long-term human lymphoma cell line. Addative effects were noted with CCNU, ara-C, prednisolone, DDP, VP-16, and Yoshi, and mild synergistic effects with BLEO and CS. Adriamycin reduced the killing ability of BCNU and MeCCNU when applied simultaneously. This antagonistic effect was canceled by sequential incubation with each drug. It appears that no significant synergism can be expected by simultaneous pairing of adriamycin with some currently available chemotherapeutic agents.


Fab dimers of antitumor immunoglobulins as covalent carriers of daunomycin. Fab dimers were prepared by pepsin digestion from the immunoglobulin fraction of a rabbit antiserum towards the Yac Moloney virus lymphoma cells. Daunomycin was attatched to these (Fab)2 by covalent binding. The resultant conjugates exerted pharmacological toxic activity and specificity towards Yac target cells similar to that observed previously with conjugates of intact anti-Yac IgG. The activity was manifested both in vitro by inhibition of RNA synthesis and by the effect of reduction of the growth of the tumor cells in vivo after short exposure to the conjugates. The potential advantage of using an IgG molecule devoid of its Fc portion is discussed.


Preparation and properties of the O-methyl derivatives of 9-beta-D-arabinofuranosyladenine. The previously reported resistance of 9-substituted adenines to ring alkylation in alkaline medium was profited from to prepare all seven possible O' methyl derivatives of the therapeutically important 9-beta-D-arabinofuranosyladenine (araA) by mild methylation of the latter with dimethylsulfate in aqueous alkaline medium. All the products were fractionated and isolated in a single step on a Dowex OH- column. The sequence of elution of the various derivatives was strikingly similar to that for the O' methyl derivatives of 1-beta-D-arabinofuranosylcytosine, previously reported, suggestive of a similar sequence of acidities of the sugar hydroxyls. The products were identified by various criteria, including PMR spectroscopy, extensive data for which are supplied. The 2'-O-methyl and 3'-O-methyl derivatives of araA exhibited appreciably lower susceptibility to calf intestinal adenosine deaminase than the parent araA. The 5'-O-methyl analogue was fully resistant to enzymatic deamination.


Transfer RNA and aminoacyl tRNA synthetases in hormone dependent and independent mammary tumors of GR mice: I. Comparative study of the amino acid accepting capacity of the tRNA's in the presence of the homologous and heterologous enzymes. Transfer RNA and aminoacyl tRNA synthetases were obtained from hormone dependent and independent mammary tumors of GR mice. We have studied the possible changes in the tRNA level by comparing the specific activities of the hormone dependent and independent mammary tumor tRNA's, but no differences were observed. Differences were found in the ability of enzymes from normal male GR mice liver, independent mammary tumor and dependent mammary tumor to cross-react with heterologous tRNA.