The effect of fluoride on bone of rats fed diets deficient in calcium or phosphorus. Four groups of weanling rats were fed for 2 weeks on a diet sufficient or insufficient in calcium and/or phosphorus. Each group was divided into four subgroups which were offered distilled water supplemented with 0, 50, 75, or 150 ppm fluoride. High levels of fluoride in drinking water inhibited weight gain. This inhibition was less in rats deficient in phosphorus than when normal-phosphorus diets were offered. At a low level, fluoride was without any effect on bone ash, thickness of femoral cortical bone, and mechanical strength, as measured by maximal load, ultimate stress to breaking, and limit of elasticity. Modulus of elasticity was decreased. At higher levels fluoride tended to decrease most of these parameters, except in rats deprived of both calcium and phosphorus. The effect of fluoride was modified by lack of dietary calcium and/or phosphorus and appeared to be weaker in rats deficient in these nutrients. Lack of dietary calcium and/or phosphorus decreased bone strength more than did fluoride content of water and of bone mineral. Concentration of bone ash and thickness of femoral cortical bone were closely correlated with parameters of mechanical strength.


Resistant proteoglycans in epiphyseal plate cartilage. Variations in their distribution in relationship to age and species. The localizations of resistant proteoglycans (RPGs) in the epiphyseal plates of rats, dogs, and humans are similar. In the epiphysial plates from young rats, dogs, and humans, the RPGs form a stratum at the junction of the zones of resting and proliferating cells. Non-calcified cartilage RPGs are associated with cells which have the potential for proliferation or column organization. As the individuals age, RPGs are found in intercolumnar regions or at times are even absent. There is also a type of RPGs in calcified cartilage, including the calcified cartilage subjacent to the articular surface, in all species. In human epiphyseal plates, looser fibrillar RPGs change abruptly to a more condensed type in the zone of provisional calcification. Calcified cartilage RPGs stain more intensely with toluidine blue and may represent a different type of RPGs.


An interpretation of acute changes in plasma 45Ca following parathyroid hormone administration to thyroparathyroidectomized rats. Acute changes in plasma calcium and 45Ca were studies in young adult male thyroparathyroidectomized (TPTX) rats injected with moderate doses of parathyroid hormone (PTH). For plasma calcium changes, comparison was made between rats fasted or fed prior to PTH injection. For plasma 45Ca changes, the effect of the time of administration of the radionuclide was also studied; this included rats injected with PTH 1 h after radionuclide ("1 h 45Ca"), 18 h later ("18 h 45Ca") and more than 6 days later ("6 day 45Ca"). The results can be summarized as follows: (1) Plasma calcium changes were greater when PTH was injected into "fed" rather than into "fasted" rats. (2) PTH always produced a relative increase (compared to controls tested concurrently) in plasma 45Ca concentrations. This increase was the same in the "1 h 45Ca" and the "18 h 45Ca" group. (3) Plasma 45Ca rose at least temporarily following PTH injection in the "18 h 45Ca" group. (4) The 45Ca rise following PTH was always greater in "fed" than in "fasted" groups. (5) Plasma 45Ca specific activities (S.A.) tended to rise in the "6 day 45Ca" group and to fall in the "18 h 45Ca" group, following PTH injection. However, the 45Ca S.A. was always higher in fed than fasted groups. (6) In a few experiments in which 32P was injected with 45Ca, specific activity changes in plasma 45Ca following PTH injection were not accompanied by similar changes in 32P specific activity. These results could not be adequately explained by PTH effects on bone resorption, but the data supported the postulate that PTH controls plasma calcium concentrations by increasing transport of calcium through the osteocyte-lining cell (osteoblast) bone cell complex from the bone fluid compartment to the ECF.


The production of calcification in connective tissue and skeletal muscle using various chemical compounds. The subcutaneous injection into mice of small quantities of lead salts resulted in calcification of the dorsal fascia. Other reputed calcergens failed to produce a similar reaction. However, the injection of Zn Cl2 and KMn O4 in high doses caused damage to, and subsequent calcification of the panniculus carnosus muscle.


Calcified arteries in a gastropod.

Calcified arteries in a gastropod. The anterior aorta and major arteries of the land pulmonate snail Anguispira alternata have large calcium deposits in their walls. These deposits occur inside spherule cells, which line the walls of these vessels. The calcium occurs as amorphous calcium carbonate, in the form of intracellular spherules having alternating layers of organic and inorganic material. The spherule cells appear to be degenerating connective tissue cells; they are characterized by large numbers of spherules and by a cytoplasm which is totally empty except for a nucleus, scattered glycogen particles and a few membrane remnants. The injection of 45Ca into the foot of the snail results in rapid incorporation of this calcium into the spherule cells. Although calcium-containing spherules are now known from a wide variety of invertebrate tissues, they have not been previously recorded from arterial walls. The physiologic significance of these deposits is not known.


Proteoglycans of dentine and predentine. A density gradient system is presented by which dentine and predentine are separated, leaving an intermediate fraction, which contains material from the mineralization front. From the fractions thus obtained the proteoglycans were extracted with 4 M guanidinium chloride and further purified in urea on a DEAE column. The glycosaminoglycans extracted from dentine appeared to be protein-bound, as judged from papain digestion experiments. The polydispersity of dentine proteoglycans seemed to depend, at least partly, upon the polydispersity of its glycosaminoglycans. The materials extracted from the three tissue fractions were ellted in a similar way from Sepharose 6 B, and the amino acid composition of the preparation was determined. The differing proteoglycan patterns of the three tissue fractions indicate a metabolism related to the mineralization front.


A model-independent comparison of the rates of uptake and short term retention of 47Ca and 85Sr by the skeleton. 1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for 47Ca and 85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the 47Ca and 85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewer a priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of Ca and Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies. 85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.


A new tracer method for the calculation of rates of bone formation and breakdown in osteoporosis and other generalised skeletal disorders. 1. Evidence has accumulated that the rate of accretion (A) of calcium to bone is the sum of two fluxes; apposition involving the laying down of new bone and augmentation which is the result of slow exchange of non-surface bone calcium with plasma calcium pools as the result of solid state diffusion. 2. A method has been devised for separating A into its two components. It requires the use of 45Ca or, for clinical studies, 85Sr as a calcium tracer. Studies which are initiated with a combined accretion rate--calcium balance study, are concluded with an estimate of the exponent of the power function which has been found to describe the whole body retention of tracer from the second month onward. 3. The impulse response function of the skeleton for the tracer is then calculated, making the assumption that in any uniform volume of bone, osteoclastic resorption is a first order process. Making in addition certain simplifying assumptions, which are shown to have a modest influence on the final results, a mean rate of bone resorption can be calculated using a development of the well known Stewart-Hamilton formula. The apposition rate is calculated as the sum of the resorption rate and the calcium balance. Augmentation and diminution, defined as equal and opposite exchange processes, are given by the difference between A and the apposition rate. 4. The results of our first thirteen studies in normal subjects and patients with metabolic bone disease are presented, together with analyses of some data from the literature. It is concluded that the development of an atraumatic method for measuring rates of bone formation and resorption in the whole body would be an important advance in the study of metabolic bone disease, and this work is presented so that critical comparisons may be initiated between this tracer method and independent histological methods for measuring these parameters.


Influence of estrogens on bone resorption in organ culture. Estradiol benzoate, ethinyl estradiol, and human calcitonin were compared for their ability to inhibit the spontaneous or parathyroid extract-induced bone resorption in organ cultures of 19-day fetal rat fibulae. The criteria used for the assessment of bone resorption were: the release of 45Ca from paired prelabeled bone rudiments into the culture medium, the dry weight, and the number of osteoclasts per bone. Estradiol benzoate at concentrations of 1.3 X 10(-5) to 2.6 X 10(-4)M had no effect on the release of 45Ca from fetal fibulae or on the dry weight. Histologically, treated bones were well preserved and resembled the controls. Parathyroid extract (PTE) alone caused extensive bone resorption with numerous osteoclasts and enhanced 45Ca release without weight gain. The addition of estradiol benzoate to the culture medium did not prevent the resorptive action of PTE. Ethinyl estradiol alone provoked a dose-related inhibition of 45Ca release at concentrations of 3.4 X 10(-5) to 1.7 X 10(-4)M. However, this inhibition was accompanied by a decrease in bone dry weight and by various degrees of cellular damage. The same phenomenon was observed in PTE-treated fibulae. Human calcitonin, on the contrary, inhibited the release of 45Ca by decreasing the number of osteoclasts while the weight of the fibulae increased. The inhibitory action of ethinyl estradiol appears to be caused by a toxic effect on bone cells. It is concluded that estrogens have no direct physiological effect on bone resorption in vitro.


An X-ray diffraction investigation of age-related changes in the crystal structure of bone apatite. Evidence relating to the existence of crystalline bone mineral in vivo is considered, and bone apatite crystal structure investigated using an x-ray powder diffraction technique. Specimens of femoral compacta excised post-mortem from male and female subjects ranging from 3 1/2 years to 87 years of age have been studied. Values of the ratio c/a of bone apatite crystal cell axes for females are significantly higher (p less than 0.05) than for males. Moreover, significant change of c/a with age is observed for males (p = 0.0005) but not for females (p = 0.30). Differences in c/a are interpreted as indicating substitution of constituent ions in the bone apatite crystals.


Hyaluronic acid in supragingival dental calculus. A method is described for the isolation of heteropolysaccharides from human supragingival calculus. One component was identified as hyaluronic acid, by electrophoretic mobility, testicular hyaluronidase digestion and cetylpyridinium chloride profiles. No sulphated glycosaminoglycans were detected.


The preparation of human hemoglobin alpha-subunit and a study of its monomer-dimer association. An improved procedure for the isolation of the alpha-subunit of human hemoglobin is described. The monomer-dimer equilibrium in alpha-subunit solutions has been studied by boundary analysis in gel filtration, sedimentation velocity, sedimentation equilibrium, and cross-linking with dimethyl adipimidate. A dissociation constant has been determined from the sedimentation equilibrium data. The reaction with haptoglobin of cross-linked alpha-subunit showed that the dimer fraction wound form a stable complex.


The reaction between hemoglobin alpha-subunit and haptoglobin. The interaction between human hemoglobin alpha-subunit and porcine haptoglobin was investigated by polyacrylamide gel electrophoresis, gel filtration chromatography, sedimentation through excess alpha-subunit and gel filtration in an alpha-subunit-containing medium. No interaction was detected by the first two methods indicating dissociation of the complex during the application of these separation techniques. The latter two methods, in which the complex is studied in a medium of excess subunits, showed that haptoglobin became saturated with the binding of two alpha-subunits.


Mammalian fatty acid synthetase. III. Characterization of human liver synthetase products and kinetics of methylmalonyl-CoA inhibition. When propionyl-CoA was substituted for either acetyl-CoA or butyryl-CoA in the presence of [14C]malonyl-CoA and NADPH, the pure human liver fatty acids synthetase complex synthesized only straight-chain, saturated, 15- and 17-carbon radioactive fatty acids. At optimal concentrations, propionyl-CoA was a better primer of fatty acid synthesis than acetyl-CoA. Methylmalonyl-CoA inhibited the synthetase competitively with respect to malonyl-CoA. The Ki was calculated to be 8.4 muM. These findings provide an in vitro model and offer a direct explanation at the molecular level for some of the abnormal manifestations observed in diseases characterized by increased cellular concentrations of propionyl-CoA and methylmalonyl-CoA.


Circular dichroism and difference spectra of members of the troponin-tropomyosin system in cetyltrimethylammonium bromide. The detergent cetyltrimethylammonium bromide (CTAB) was used as a perturbant to study protein structure. Low concentrations of CTAB induced difference spectra for Ac-Trp-OEt and Ac-Tyr-OEt. The delta epsilonM values at their difference maxima were found to be 1300 at 292 nm for Ac-Trp-OEt and 400 at 287 for Ac-Tyr-OEt. These values were used to determine the number of tyrosine residues exposed in tropomyosin and troponin C, as well as the tyrosine and tryptophan residues exposed in troponin I and troponin T. In tropomyosin and troponin C all of the tyorosine residues were accessible to detergent. For TN-T, three of four tyrosines were free while the tryptophan residues were only partially exposed. In the case of TN-I both tyrosines were fully exposed but again evidence was obtained for a partially buried tryptophan chromophore. The stability of these proteins to CTAB was studies by measuring the far-uv circular dichroism spectra. Tropomyosin was quite sensitive to detergent and suffered a 60% loss in ellipticity at the concentration of CTAB used. The troponins, on the other hand, were affected to a lesser extent.


Cholera toxin and adenylate cyclase: properties of the activated enzyme in liver plasma membranes. Adenylate cyclase (EC 4.6.1.1) activity in mouse liver plasma membranes is increased fivefold when animals are pretreated with cholera toxin. The increase in activity is detectable within 20 min of an intravenous injection of the toxin. The response of the control and cholera-toxin-activated adenylate cyclase to hormones, GTP, and NaF is complex. GTP causes the same fold stimulation of control and toxin-activated cyclase, but glucagon and NaF remain the most potent activators of liver adenylate cyclase irrespective of whether the enzyme is activated by cholera toxin. Determination of kinetic parameters of adenylate cyclase indicates that cholera toxin, hormones, and NaF do not change the affinity of the enzyme for ATP-Mg nor do they alter the Ka for free Mg2+. High concentrations of Mg2+ inhibit adenylate cyclase that is stimulated by either cholera toxin, glucagon, or NaF. These same Mg2+ concentrations have no effect on the basal activity of the enzyme or its activity in the presence of GTP.


Some observations on the interaction of dopamine-beta-hydroxylase and its natural inhibitors in the rat brain. The difficulty of assaying dopamine beta-hydroxylase (DbetaH) (EC 1.14.17.1) has been circumvented by including N-ethylmaleimide (5 X 10(-2) M) in the incubation mixture along with a small amount of Cu2+ (20-60 muM). Such a procedure ensures that the maximum DbetaH activity is assessed in all extracts. As a result, the absolute levels of DbetaH in various regions of the rat brain have been established. The DbetaH values obtained are higher by 40% in the hypothalamus and 20% in the cerebral cortex, spinal cord, and caudate nucleus than those previously reported. The mechanism of the synergic effect seen when N-ethylmaleimide and Cu2+ are combined is not presently understood.


The purification of porcine haptoglobin by affinity chromatography with concanavalin A-Sepharose. Methods designed for the isolation of human haptoglobin (Hp) were found insufficient when applied to pig plasma due to the formation of a material tentatively identified as albumin dimer. Small scale separation is possible by preparative polyacrylamide gel electrophoresis. Larger scale purification from nonglycoprotein contaminants such as albumin dimer is achieved by affinity chromatography using immobilized concanavalin A. Porcine haptoglobin is microheterogeneous. More than 14 components, partially resolveable by gel filtration, were detected.


Chromosomal characterisation of five lepidopteran cell lines of Malacosoma disstria (Lasiocampidae) and Christoneura fumiferana (Tortricidae). Chromosome number and morphology have been examined in four established cell lines (Md63, Md66, Md108, and Md109) of the forest tent caterpillar, Malacosoma disstria Hübner, and one (Cf124) of the spruce budworm, Choristoneura fumiferana (Clemens). Chromosome number distributions of Md63 (mode = 112) Md108 (mode = 103), Md109 (mode= 103), and Cf124 (mode = 110) overlap sufficiently to prevent identification of individual lines by number alone. However, Md66 is exceptional in possessing a modal number of 157. One large chromosome occurs in cells of all lines. The presence of this chromosome, the lack of any distinct polyploid series among chromosome numbers encountered, and the general inverse relationship between number and size of chromosomes, suggest that the high level of heteroploidy characteristic of these and other lepidopteran cell lines reflects not only a possible polyploid origin but also extensive chromosomal rearrangement and fragmentation. Tolerance for such change is attributed to the holokinetic organisation of lepidopteran chromosomes. A distinct heteropycnotic body is present in about 10% of Cf124 cell nuclei, and can be used as a marker for this line. This body may represent the sex chromatin normally encountered in somatic cells of female C. fumiferana.


The effect of accessory chromatin on chiasma distribution in maize. From an analysis of metaphase I bivalent configurations in Zea mays L. it was possible to determine the effects of two supernumerary elements on chiasma formation. Both the B chromosome and abnormal chromosome 10 increased chiasma frequency. In addition to enhancing total exchanges, both elements caused a redistribution of chiasmata from distal to more proximal locations.


The genetic relationship between the Hbb locus and body size in a population of mice divergently selected for six-week body weight. Both pleiotropy and linkage were examined as possible explanations for the fixation of the Hbb3 allele in the six Large lines of a population of mice divergently selected for six-week body weight (six replicates in each direction and six controls). A survey of over 1200 individuals in the lines still segregating at the Hbb locus excluded pleiotropy as a possible explanation. The results showed a nonsignificant effect of haemoglobin genotype on body weight. The linkage relationship of the Hbb locus was examined using a backcross mating system. The Hbb3 c+ region (chromosome 7) of a Large line was backcrossed into its corresponding Small line (Hbb4 c). The resultant difference in body weight between the two segregants (Hbb8 c+ [Hbb4 c; Hbb4 c/Hbb4 c) was measured. The results suggested linkage as the most plausible explanation for the fixation of the Hbb4 allele in the six Large lines.


Improved resolution of the meiotic chromsomes in both sexes of Euxoa species and their hybrids (Lepidoptera: noctuidae). An air drying and Giemsa staining technique produces consistently good quality cytological preparations when applied to different species of Euxoa (Lepidoptera: Noctuidae) and, in particular, it allows an imporved resolution of the meiotic chromosomes in both sexes. All species so far investigated have a basic haploid chromosome complement of n (male) = 31(XX): n(female) = (XY). A single chiasma per individual bivalent is clearly visible in the male sex. Some chiasmata are formed in interstitial positions, but, by metaphase I, they have all undergone complete terminalization while the bivalents orient axially on the first division spindle. Direct evidence for lack of chiasma formation in the 31 hormorphic bivalents in the female sex is reported for the first time for species of Noctuidae. Evidence in favor of an XY system in the female sex is discussed. Preliminary studies of the meiotic divisions in hybrid material reveal the presence of cryptic structural differences between certain taxa, and will help to elucidate taxonomic problems within this complex genus.


The structlre of pili (fimbriae) of Moraxella bovis. Cells from rough and smooth colonies of Moraxella bovis were examined by electron microscopy utilizing both shadowing and thin sectioning techniques. Pili were found on the surfaces of cells from rough but not smooth colonies. Pili had a peritrichoud distribution and appeared as delicate (6.5-8.5 nm in diameter), elongated unbranched filaments. When bacteria were sectioned pili did not contain central pores and appeared to originate from opacities on the surface of the cell wall.


Induction of bovine polioencephalomalacia with a feeding system based on molasses and urea. Polioencephalomalacia (PEM), a disease first described in the United States and related to intensive beef production, appeared in Cuba coincident with the use of a new, molasses-urea-based diet to fatten bulls. Because the only experimental means so far of reproducing PEM has been with amprolium, a structural analog of thiamin, the present study attempted to induce the disease using the molasses-urea-based diet. Six Holstein bulls (200-300 kg) were studied during consumption of three successive diets: 1) commercial molasses-urea-restricted forage diet of Cuban feedlots, 2) a period in which forage was gradually withdrawn and 3) a forage-free diet composed only of molasses, urea and fish meal. PEM was reproduced in this way. At ten-day intervals, blood concentrations of glucose, lactate, pyruvate and urea were measured, as well as when clinical signs of PEM appeared. The signs, clinical course and lesions of the experimentally induced disease were comparable to those of field cases. The biochemical results suggested a block in pyruvate oxidation as in PEM elsewhere in the world. No evidence existed of urea intoxication. In addition, brain and liver concentration of total thiamin from field cases and normal animals were found to be similar.


Phagocytic acitivity of bovine leukocytes during pregnancy. The phagocytic competence, measured as the total number of polymorphonuclear leukocytes per mm3 which phagocytosed Staphylococcus aureus, strain 321, in vitro, was determined in eight cows during complete pregnancies. Such leukocytes are referred to as "Active PMN'S". There was a gradual decline in the number of these cells from conception to a minimum between the 16th and 20th weeks of pregnancy, followed by a steady increase to the cessation of lactation when a marked drop occurred, after which there was an increase to a maximun during the second week prepartum. From this maximum there was a rapid decrease to an absolute minimum during the first week after parturition. From the second week postpartum there was a gradual increase to conception. The correlation coefficient (r) of number of active PMN'S with time before conception was -0.474 )p-0.01). There were significant differences (p=0.01) in numbers of active PMNS Among the eight cows. It was found that the cows fell into two groups, one whose members had, overall, significantly more active PMNs (p=0.001) than those in the second group. The between cow differences may have been due to 1) age, since the cows with the highest numbers of circulating active PMNs were younger than those in the other group of 2) the combined stress of pregnancy and lactation, as those cows which were both pregnant and milking had the lowest numbers of active PMNs.


Fusariotoxicosis from barley in British Columbia. I. Natural occurrence and diagnosis. Clinical sickness was observed in domestic ducks, geese, horses and swine during October 1973. All species showed upper alimentary distress with mortalities occurring in the geese. Barley derived from a common source had been fed. Examination of the barley revealed invasion by Fusarium spp and detection of a high level of dermatitic fusariotoxins.


Fusariotoxicosis from barley in British Columbia. II. Analysis and toxicity of syspected barley. Fusariotoxin T-2, a trichothecene, was tentatively identified in barley samples which caused field outbreaks of mycotoxicosis in British Columbia. Geese died when fed the contaminated barley experimentally but mice were little affected after long term feeding. The methods used in the laboratory for trichothecene extraction and identification of T-2 toxin are described.


The indirect hemagglutination test for the detection of antibodies in cattle naturally infected mycoplasmas. Stable mycoplasma antigens for the indirect hemagglutination test (IHA) were prepared employing glutaraldehyde treated sheep erythrocytes sensitized with Mycoplasma agalactiae subsp. bovis and Mycoplasma bovigenitalium antigens. Employing these antigens mycoplasma antibodies were detected in sera from cattle which had mastitic symptoms due to natural infection with either M. agalactiae subsp. bovis or M. bovigenitalium. A total of 200 cows from four herds were examined at varying intervals for the presence of M. agalactiae subsp. bovis and for the detection of antibody using growth inhibition and IHA tests. Mycoplasmas were isolated from 37 animals. Growth inhibiting antibody was detected from 56 of the 200 animals. In the IHA tests, antibody titer greater than or equal to 1:80 were detected in 148 animals, 76 of these having antibody titers greater than or equal to 1:160, while sera of 116 normal control animals had no growth inhibiting antibody and none had IHA antibody titers greater than 1:40. M. bovigenitalium was isolated from the milk of three of 26 animals in a fifth herd during an outbreak of mastitis. Growth inhibiting antibodies were demonstrated in the sera of ten of the 26 animals. However, the IHA test detected antibody titers of greater than or equal to 1:160 in 13 animals and of 1:80 in one of the 26 animals. To determine the specificity of the IHA tests, M. agalactiae subsp. bovis and M. bovigenitalium antigens were reacted with rabbit hyperimmune typing sera produced against 12 species of bovine mycoplasmatales. Homologous antisera showed IHA antibody titers of 1:1280 and 1:2560 against M. agalactiae subsp. bovis and M. bovigenitalium respectively, whereas heterologous antisera showed IHA antibody titers of less than or equal to 1:20. Also eight type-specific bovine antisera were reacted with M agalactiae subsp. bovis and M. bovigenitalium antigens in homologous and heterologous tests. Homoogous reactions showed IHA antibody titers greater than or equal to 1:320, whereas heterologous reactions showed IHA titers of less than or equal to 1:20. This IHA test promises to be useful for the detection of bovine mycoplasma antibodies in sera from cattle infected with M. agalactiae subsp. bovis or M. bovigenitalium. Thes test is sensitive, reproducible and specific and the technique is relatively simple and rapid. The antigens were stable for at least seven months.


Mercury and mink. I. The use of mercury contaminated fish as a food for ranch mink. Adult female and juvenile ranch mink were fed rations containing 50 and 75% of fish containing 0.44 ppm total mercury over a 145 day period. There was no clinical or pathological evidence of intoxication in these animals and mercury concentrations in tissue appeared to be at a level below that associated with toxicity.


Mercury and Mink. II. Experimental methyl mercury intoxication. Adult female mink were fed rations containing 1.1, 1.8, 4.8, 8.3 and 15.0 ppm mercury as methyl mercury chloride over a 93 day period. Histopathological evidence of injury was present in all groups. Mink fed rations containing 1.8 to 15.0 ppm mercury developed clinical intoxication within the experimental period. The rapidity of onset of clinical intoxication was directly related to the mercury content of the ration. Mercury concentration in tissue of mink which died were similar, despite differences in mercury content of the diets and time of death. The average mercury concentration in the brain of mink which died was 11.9 ppm. The lesions of methyl mercury poisoning are described and criteria for diagnosis are discussed.


Studies on the response of ewes to live chlamydiae adapted to chicken embryos or tissue culture. Ewes infected before gestation with chicken embryo or tissue culture adapted chlamydial strain B-577 were challenge inoculated with the homologous strain at four to 18 weeks of gestation. The ewes responsed with group specific complement fixing antibody titers of 1:8 to 1:256 by the second week after initial infection. A secondary antibody response in the surviving challenge inoculated ewes occurred at the time of lambing and reached titers of 1:32 to 1:256 by the second week after parturition. Group specific complement fixing antibodies did not appear to play a significant role in resistance to chlamydial infection. Ewes infected with the chicken embryo adapted strain B-577 excreted chlamydiae in their feces 60 days after inoculation. However, chlamydiae were not recovered from feces of ewes infected with the tissue culture adapted strain B-577. Placentas of ewes challenge inoculated by the intravenous route were consistently infected. Chlamydiae were recovered from placentas, some fetuses and lambs. In two instances when challenge inoculation was given by the intramuscular route, infection was detected only by the direct fluorescent antibody method.


Effect of trauma on plasma glucagon and insulin concentrations in sheep. Portal plasma glucagon and insulin concentrations were measured before and after acute trauma (liver biosy). The trauma was sufficient to increase glucagon concentrations and depress insulin concentrations. These changes were associated with a marked hyperglycemia. Infusion of glucagon was insufficient to prevent stress inhibition of insulin secretion. The stimulation of glucagon secretion and inhibition of insulin secretion were of about one hour duration. These findings indicate that glucagon and insulin in conjunction with the nervous system may play an important role in the development of stress related hyperglycemia.


Experimental production of infectious bovine keratoconjunctivitis: comparison of serological and immunological responses using pili fractions of Moraxella bovis. The effect of vaccinating cattle and mice on the development of keratoconjunctivitis was studied. Cattle were vaccinated with whole cells, disrupted cells and pili fractions of three strains of Moraxella bovis. Mice were vaccinated with pili fractions of three strains. The resistance of all vaccinated animals was challenged with virulent cultures of M. bovis. In an attempt to correlate the response seen after vaccination and challenge with a pili fraction of M. bovis, vaccinated cattle and mice were grouped on the basis of signs of disease manifested and compared on the basis of serological responses. Serum samples were tested for antibodies by a gel diffusion precipitin test. A greater number of the sera of resistant cattle had antibodies to the homologous pili antigen than those of vaccinated nonresistant cattle. Cattle vaccinated with disrupted cells were not resistant to infectious bovine kerato-conjuctivitis and their sera lacked antibodies against the pili antigens. Vaccinated mice were more resistant to infectious bovine kerato-conjuctivitis and their sera lacked antibodies against the pili antigens. Vaccinated mice were more resistant to challenge exposure by homologous than heterologous cultures. A greater number of the sera of resistant mice had antibodies to pili antigens than nonresistant mice.


Mycotoxin determinations on animal feedstuffs and tissues in Western Canada. Results of examination of specimens of plant or animal origin for various mycotoxins are presented. Analyses for aflatoxins and ochratoxins were most frequently requested, usually on the basis of visible mouldiness. Aflatoxin B1 was found in one of 100 specimens at a level of 50 ppb in a sample of alfalfa brome hay. Ochratoxin A was detected in seven of 95 specimens comprising six samples of wheat at levels between 30 and 6000 ppb and one sample of hay at a level of 30 ppb. An overall detection rate of 4.2% involving significant levels of potent mycotoxins suggests that acute or chronic mycotoxicoses may occur in farm livestock or poultry more frequently than presently diagnosied.


Temperature sensitivity studies on selected strains on Mycoplasma gallisepticum. Mycoplasma gallisepticum (MG324), a tylosin resistant strain of low virulence, was compared with four other strains with respect to their survival at temperatures from 46.1 to 48.9 degrees C. MG324 was found to be more resistant than the other strains tested.


Lead and mercury residues in kidney and liver of Canadian slaughter animals. Liver and kidney samples were collected from Canadian slaughter animals during the winter of 1973-1974. A total of 256 samples were analyzed for lead. Mean lead levels of 1.02 ppm in poultry liver, 1.04 ppm in bovine liver, 1.02 ppm in bovine kidney, 0.73 ppm in pork liver and 0.85 ppm in pork kidney were found. A total of 265 samples were analyzed for mercury. Mean mercury levels of 0.003 ppm in poultry liver, 0.007 ppm in bovine liver, 0.008 ppm in bovine kidney, 0.001 ppm in pork liver and 0.013 ppm in pork kidney were found. All levels detected were below the Canadian official tolerance of 2 ppm for lead and administrative tolerance of 0.5 ppm for mercury.


Infleuce of dietary levels of vitamin E and selenium on tissue and blood parameters in pigs. Eighteen barrows approximately three weeks of age were used in a 3 X 3 factorial arrangement to investigate the effect of level of supplemental vitamin E and selenium on tissue and blood parameters. Tissue selenium concentrations increased in a quadratic manner with increased selenium intake with kidney tissue containing considerably greater concentrations than liver, heart or muscle. Supplementation of the diet caused a three-fold increase in serum selenium within the first week with a slight tendency to further increases in subsequent weeks. Serum vitamin E of unsupplemented pigs declined by fifty percent during the experiment, whereas supplemental vitamin E resulted in increased serum vitamin E. There was a considerable viration in percent peroxide hemolysis. Correlation of -0.63 between percent peroxide hemolysis and vitamin E intake and -0.85 between percent peroxide hemolysis and serum vitamin E were observed.


Epidemiological field studies of animal populations. Numerous survey designs have been developed for epidemiological field studies of human populations, most of which are also applicable to field studies of animal poulations. Each design has its own advantages and disadvantages. The final design selected for a particular study depends upon such factors as the overall purpose of the study, the geographic dimensions of the study area, the diseases incidence or prevalence and species to be studied as well as the planned use for the data. Population dynamics including the distribution and density of the species to be studied are factors that should also be considered in the initial design of a study. A surveillance system, using mailed questionnaire data and a subsequent survey using direct interviews of validate the data in a statewide study of swine birth defects are used to illustrate some of the techniques that can be applied to domestic animal populations in a fairly large geographic area. The type of data collected, its use and its limitations are also considered.


Bovine mastitis in Ontario due to Mycoplasma agalactiae subsp. bovis. Bovine mastitis caused by Mycoplasma agalactiae subsp. bovis was first diagnosed in 16 of 55 cows in an Ontario herd in Feburary 1972. A total of 182 of 598 (30.4%) cows from 33 of 64 (51.5%) farms in widely separated areas of the province were culturally positive. Herd incidence varied from 15 to 40% with one closed herd having an incidence of 61%. Four herds were investigated culturally and serologically by the growth inhibition test for 15 months. In the acute phase the organism was present in the milk in extremely high numbers and could still be isolated from a few cows after eight to 12 months. The sera from 89.5% of the animals with clinical mycoplasma mastitis produced a zone of surface "film" and/or colony inhibition and some cows remained positive for six to 12 months. The disease was experimentally reproduced with a pure culture of the organism isolated from the milk of a cow from one of the herds.


Effects of glucagon and insulin on lipolysis and ketogenesis in sheep. The hepatic and portal productions of acetoacetate and beta-hydroxybutyrate and lipolysis were studied in normal and insulin-controlled alloxan-diabetic sheep. Since hyperinsulinemia is associated with glucagon administration, the latter group of sheep were used to maintain constant plasma insulin levels. After control values were obtained glucagon was infused intraportally at 90 mug/hr for two hours. The ketone body production by portal drained viscera was not significantly affected by glucagon. In alloxanized sheep, glucagon significantly (P less than 0.01) increased net hepatic production of acetoacetate (from -0.54 +/- 0.08 to 0.46 +/- 0.07 g/hr). Lipolysis also increased. However, in the normal sheep, hyperinsulinemia prevented any stimulatory effect of glucagon on hepatic ketogenesis and lipolysis. Therefore, while glucagon appears capable of stimulating ketogenesis andlipolysis, these effects are readily suppressed by insulin.


The role of colorstrum on the occurrence of immunoglobulin G subclasses and antibody production in neonatal goats. Quantitative determinations of IgG1 and IgG2, in one group of colostrum-fed and one group of colostrum-deprived neonatal goats revealed that the occurrence of the IgG1 subclass preceeded that of the IgG2 in both cases. In the colostrum-fed animals the IgG2 appeared, on an average, in the fourth week of life whereas in the colostrum-deprived animals the IgG2 was detected as early as three weeks after birth. At the age of twelve weeks the mean concentrations for IgG, and IgG2 were higher in the animals deprived of colostrum. The immune response to human gamma globulin was studied in colostrum-fed and colostrum-deprived neonatal goats which were immunized at birth and again after four and eight weeks. Following the first two antigen administrations a significantly higher response was obtained in the colostrum-fed neonates. However, the third injection determined a similar response in both groups. A marked suppressive effect on the immune response was observed in colostrum-fed neonatal goats when specific antibodies were present in the colostrum after preimmunization of the mothers with human gamma globulin.


A comparison of techniques for the quantitative analysis of hyaluronic acid in equine synovial fluid. A comparison of methods of preparing the hyaluronic acid of equine synovial fluid for quantitative spectrophotographic analysis is presented. A new method is proposed which appears superior to the previous methods.


Some leptospira agglutinins detected in domestic animals in British Columbia. During a period of six years 7,555 bovine sera, 421 canine sera, 251 porcine sera and 135 equine sera were tested for agglutinins to Leptospira interrogans serotypes canicola, grippotyphosa, hardjo, icterohemorrhagiae, pomona and sejroe. The bovine sera reacted predominantly with hardjo and/or sejroe at a rate of 15% compared to 3.5% with pomona. Breeding or abortion problems were associated with pomona but not with sejroe/hardjo agglutinins. The canine sera reacted to canicola (9.9%y and icterohemorrhagiae (5.4%), tcted predominantly with canicola (8.9%) and icterohemorrhagiae (8.1%).


Hypersensitivity pneumonitis: experimental production in calves with antigens of Micropolyspora faeni. Pneumonitis was induced in calves by exposure to aerosols of Micropolyspora faeni with or without prior sensitization of the animals by subcutaneous injection of antigen. The pneumonitis primarily involved centrolobular areas and was characterized by alveolar septal thickening and loss of air space by cellular infiltration. Vasculitis and focal haemorrhage occurred in certain individuals and haemoproteinaceous exudate appeared within septa and alveolar lumina. The pneumonitis was compared with human farmer's lung, pneumonitis of housed cattle and other experimental hypersensitivity pneumonitides.


Values of three coagulation screening tests of precolostral calves. Prothrombin times, partial thromboplastin times and platelet counts were performed to determine normal values and to screen for coagulation defects of precolostral calves. The precolostral calves were in two groups: one group of a few calves was tested two years before the second larger group. The results for both groups were similar. The tests were performed on postcolostral calves and on mature cows to compare their values with those of precolostral calves. The mean values of prothrombin times and partial thromboplastin times of precolostral calves in the first group were 18.8 seconds and 54.8 seconds respectively. The mean values of prothrombin times and partial thromboplastin times of precolostral calves in the second group were 18.8 seconds and 50.8 seconds respectively. The mean platelet count was 422,400/cmm for the first group and 482,800/cmm for the second group.


The determination of hemoglobin and myoglogin residues as a parameter for testing heat exposure in back bacon. The use of an extraction of the heme pigments hemoglobin and myoglobin as a test for the heat exposure of back bacon was investigated by treating back bacon at varying temperatures of 50-70 degrees C and times of two to 180 minutes and observing the effect on the absorbance of heme pigment residue after nitrite oxidation. Absorbance at 409 nm was used in place of the more usual 540 nm to provide greater sensitivity in the detection of heme. A decrease in residual heme pigments was time-dependent, particularly at lower temperatures. In view of this factor and the complex nature of the heat exposure of a large block of back bacon, the application of this test would require a calibration of each process. Alternatively, limits to the amounts of heme pigment residue could be set. The heme pigment test is useful in its simplicity and overcomes difficulties associated with the coagulation and enzyme tests.


The bioavailability, dispostion kinetics and dosage of sulphadimethoxine in dogs. The disposition kinetics of sulphadimethoxine were studied in six normal beagle dogs after intravenous injection of a single dose (55 mg/kg). The median (range) distribution and elimination half times of the drug were 2.36 (2.06-3.35) hours and 13.10 (9.71-16.50) hours, respectively. Total body clearance of the drug had a median value of 21.7 ml/kg/h and a mean value of 21.4 ml/kg/h. While the overall tissue to plasma level ratio (k12/k21) of the drug was 0.55 after distribution equilibrium had been attained, analogue computer simulated curves showed that at 24 hours the fractions (percentage) of the dose in the central and tissue compartments were 12 and 11%, respectively. The drug was shown, by equilibrium dialysis method, to be highly bound to plasma proteins (greater than 75%) within the usual therapeutic range (50 to 150 mug/ml) of plasma levels. The systemic availability of sulphadimethoxine from the oral suspension was 32.8% (22.5-80.0). Since the absorption half time, 1.87 (0.86-3.22) hours, was considerably shorter than the half-life, 13.10 (9.71-16.50) hours, of the drug, the rate of absorption would have little influence on the dosage regimen. Based on the experimental data obtained, a satisfactory dosage regimen might consist of a priming dose of 55 mg/kg by the intravenous route and maintenance doses of either 27.5 mg/kg of sulphadimethoxine injection given intravenously or 55 mg/kg of the oral suspension administered at 24 hour intervals. The adequacy and duration of therapy will depend upon the clinical response obtained.


A simple technique for mass cultivation of Campylobacter fetus. Studies using 86 media for maximum growth of Campylobacter fetus for antigen production showed that a diphasic medium (solid base with liquid overlay) was most suitable. The solid base was double strength cystine heart agar. The liquid overlay was thioglycollate medium of Brewer (135-C) without agar. This medium yielded maximum growth of C. fetus in six days with good motility, less clumping and less filament formation than all other media tried.


Investigation of maturation requirements for Ostertagia ostertagi and Cooperia oncophora larvae. Infection of parasite-free six to eight week old calves with doses of 50,000 mixed Ostertagia ostertagi and Cooperia oncophora larvae varying in age from seven to 42 days did not reveal a significant larval maturation requirement.


Strongyle infections in ponies. I. Response to intermittent thiabendazole treatments. A group of seven ponies naturally infected with large numbers of small strongyles and raised under conditions to minimize reinfection were treated periodically over a three year span with thiabendazole at the rate of 44 mg/kg body weight. Based on the absence of worm eggs in the feces following each treatment, thiabendazole removed the adult strongyles present with a new population subsequently developing by maturation of inhibited larvae. It took as many as four or five treatments to eliminate or reduce significantly the worm burdens present in the ponies under the conditions of this study. Strongyle eggs started to reappear in the feces about six weeks after treatment and following the first treatment the mean egg counts rose to the pretreatment level. On successive treatments the interval for worm eggs to appear in the feces lengthened and mean egg counts never rose quite as high as immediate pretreatment levels. Hematological changes were not marked, although a small steady increase in the mean hemoglobin values and an equivalent small decrease in the mean eosinophil counts occurred in all ponies following each successive treatment. The study supports the rationale of regular anthelmintic treatment of horses in that even in the absence of reinfection, new burdens of adult worms develop following treatment.


Serum ampicillin levels in the calf: influence of dosage, route of administration and dosage form. Holstein bull calves received ampicillin sodium by the intravenous, intramuscular and subcutaneous routes and ampicillin trihydrate by the intramuscular route, at a dosage of 5 mg/kg. In addition ampicillin sodium and ampicillin trihydrate were given at a 12 mg/kg dosage intramuscularly. The serum ampicillin concentrations were determined at five, 30, 60, 120, 180, 240 and 300 min after drug administration and at 360 min after ampicillin trihydrate injection. Intravenous administration gave a high initial level (16.2 mug/ml) at five min that declined to below 1 mug/ml by 120 min. Subcutaneous administration produced the lowest initial levels of drug but concentrations of drug detected did not differ significantly from the intramuscular administration at any sampling interval. The 12 mg/kg intramuscular ampicillin sodium dosage produced significantly higher levels than the 5 mg/kg dosage only at five min. Ampicillin trihydrate gave higher levels than ampicillin sodium at all times except 30 min (5 mg/kg) and five min (12 mg/kg). The serum ampicillin disappearance study (5 mg/kg intravenous) gave a two component bi-exponential curve. Kinetic analysis of the first component showed a C01 (theoretical initial conc) of 44.8 mug/ml, a ke1 (rate constant of disappearance) of 0.064 mug min and a t1/21 (calculated half-life) of 10.8 min. The Co2, ke2 and t1/22 of the second component were 6.2 mug/ml, 0.0157 mug/min and 46.2 min respectively.


The effect of route of immunization on the lapine immune response to killed Pasteurella haemolytica and the influence of aerosol challenge with the live organism. Appearance of anti-Pasteurella haemolytica antibody in the serum and broncho-alveolar washings of rabbits is independent of the route of immunization and is similar in both locations. The most influential factor in development of a humoral response is exposure to live P. haemolytica and prior exposure to the killed bacterium has no significant effect upon titre determined following aerosol challenge with live organisms.


Strongyle infections in ponies. II. Reinfection of treated animals. Five of seven ponies whose strongyle worm burdens had previously been removed or markedly reduced by repeated thiabendazole treatments were reinfected with doses ranging from 100,000 to 500,000 small strongyle infective larvae. Reinfection of ponies resulted in the development of clinical signs characterized by abnormal feces, marked loss of weight and delayed shedding of winter hair coats. An abrupt increase in circulating eosinophils occurred during the first three weeks following reinfection. Patent infections developed in all ponies with worm eggs appearing in the feces from 12 to 15 weeks after receiving infective larvae. Worm egg outputs followed a cyclic pattern with approximately four to five peaks in egg output per year. There was an abrupt drop in the high worm egg counts in two untreated ponies approximately two and a half years after reinfection. No worms were recovered in the feces of these animals when they were subsequently treated, suggesting that a depletion in the number of inhibited larvae present in these ponies might have occurred.


Pathological changes in chickens, ducks and turkeys fed high levels of rapeseed oil. Rations containing 25% of either  regular rapeseed oil (36% erucic acid), Oro rapeseed oil (1.9% erucic acid), soybean oil or a mixture of lard and corn oil were fed to chickens, ducks and turkeys. The regular rapeseed oil ration caused growth depression, increased feed conversion and anemia in all species. All the ducks and some of the chickens fed the regular rapeseed oil ration died. These dead birds were affected with hydropericardium and ascites. No deaths in the turkeys could be attributed to the regular rapeseed oil ration but some turkeys fed this ration had degenerative foci characterized by infiltrations of histiocytic and giant cells in the myocardium. Severe fatty change in the heart, skeletal muscles, spleen and kidney was found at an early age in all birds fed the regular rapeseed oil ration. Less severe fatty change but no other lesions were found in birds fed the Oro rapeseed oil and soybean oil rations.


Quantitative assessment of the morphology of the pig's head used as a model in surgical experimentation. Part 1: Methods of Measurements. Thirty-two surface measurements were described for assessment of the effect of complex surgical operations on the skeleton of the face in pigs. The methods of measurements imitate those of anthropometry. The surface measurements can complement cephalometry with data about the changes in the soft tissue and thus improve the documentation of the effect of surgery. This paper can help in the evaluation of complicated osteotomy procedures using the pig as the animal model, for facial reconstruction research in humans.


In vitro effects of 2,4-dichlorophenoxy acetic acid (2,4-D) on bovine cells. Bovine fetal muscle cells were exposed to culture media containing 2 mg and 20 mg per liter of 2,4-dichlorophenoxy acetic acid (2,4-D) for varying intervals to determine the in vitro response of mammalian cells to this compound. The concentrations of 2,4-D used were comparable to those used in spray programmes although the residues normally found in pasture are much lower since 2,4-D is rapidly degraded under field conditions. Untreated and treated cultures were analyzed for total cell count, mitotic index and the percentages of differentiating and degenerating cells. The response of cultures to treatment was similar irrespective of the concentrations of 2,4-D used although in higher concentrations there was an initial drop in mitotic index. Other changes noted in treated cultures included an increase in differentiating and degenerating cells compared to those in control. The mitotic cells in treated cultures exhibited unipolar and tripolar spindles and a variety of other abnormalities including malorientation of the mitotic apparatus in relation to the axis of the cell. Myoblasts in initial stages of myogenesis were noted to be in mitosis in treated cultures suggesting that 2,4-D may have a stimulatory effect on myoblasts which in normal myogenesis are in post mitotic stage.


Complement fixation titers in cattle following intranasal inoculation of Hemophilus somnus. Five bulls were inoculated intranasally with a live culture of Hemophilus somnus originally isolated from a clinical case of Hemophilus septicemia. Preinoculation and postinoculation blood samples were taken at weekly intervals for nine weeks for measuring complement fixation titers and daily postinoculation temperatures were taken for one week. Three animals had transient fever and slight lethargy was observed in two animals had a transitory rise in complement fixation titers in the second to fifth weeks postexposure while one animal which had been seronegative on preinoculation testing produced little serological response to the organism. The experiment demonstrated that the nasal instillation of young cattle using an originally pathogenic H. somnus isolate is capable of stimulating only transitory complement fixation antibody titer.


Twelfth rib resection as an approach for portal vein cannulation in sheep. A surgical technique involving resection of the twelfth rib was used to insert silastic cannulas into the portal veins of three sheep to study amino acid metabolism. Good exposure to the vein was achieved by this method although it required positive ventilation due to the penetration of the thoracic cavity. All cannulas were buried subcutaneously and exteriorized near the dorsal midline. This facilitated continuous infusion into the portal cannula without disturbing cannula placement.


Neurofibrillary tangles in the dementia of "normal pressure" hydrocephalus. Routine neuropathological examination could not explain the dramatic improvement exhibited by one patient with "normal pressure" hydrocephalus after shunting. The improved patient contrasted remarkably with the unchanged condition of four others also shunted successfully. The five brains were analysed by quantitative morphometry to determine the degree of neurofibrillary tangle formation in mesial temporal neurons. The density of tangle-bearing nerve cells in the four unimproved cases was markedly greater than in age-matched control brains from nineteen normal subjects, and fell in the same range as that of eight dements with neuropathologically confirmed Alzheimer's disease. The density of the one who recovered was within normal limits. The duration of dementia before shunting, and the total duration of dementia in these five patients rank in the same order as their degree of neurofibrillary formation. Furthermore, a positive linear correlation exists between the Tangle Indices and the total duration of dementia. The data suggest that early diagnosis may improve the chances of reversing the dementia of normal pressure hydrocephalus before histological alterations prove too severe.


Some neurophysiological effects of cerebellar stimulation in man. This paper presents the results of neurophysiological studies of the effects of cerebellar stimulation on H reflexes, late reflexes, blink reflexes, evoked potentials and EEG patterns in 18 human subjects (Male 13, Female 5, Age 25.8+/-10.0, Epileptic 9, Cerebral Palsy 9). In addition to the effects of cerebellar stimulation on the H reflex studies on soleus we assessed V1 and V2, "late" responses (Upton et al., 1971), cortical somatosensory evoked potentials (SSEP) after median nerve stimulation, and visual evoked responses (VER) after flash stimulation. Experiments were extended to assess recovery curves of all the potentials and we examined the effects of changes on the rate or voltage of cerebellar stimulation. Cerebellar stimulation was inhibitory to all the responses except the visual evoked potentials. Serial studies in five patients produced consistent results. Preoperative and postoperative results were compared in two patients with no significant difference in the results in the absence of cerebellar stimulation. Ipsilateral cerebellar stimulation (CS) had the greatest inhibitory effects on H, V1 and V2 responses in the arm and leg whereas contralateral CS produced the greatest effects on cortical SSEPs. There was a greater bilateral effect on SSEPs and reflex responses after right CS than left CS and this may be the first indication of "dominance" in the cerebellar hemispheres. Cerebellar stimulation in patients on diphenylhydantoin produced minimal effects on SSEP's and this observation has led to further studies in patients taking diphenylhydantoin. Recovery of amplitude of the reflex and cortical responses took eight to 30 minutes after one minute of cerebellar stimulation. Serial CS of one minute on and one minute off produced increasing inhibition of SSEP's and reflexes for up to five stimulations. Recovery after cessation of cerebellar stimultion was associated with rebound excitation in six patients, the rebound being noted in the amplitude of H reflexes and SSEP's as well as in the frequency of paroxysmal spike and wave discharges in the EEG. The correlation of the results of such quantitative neurophysiological tests with clinical improvement may allow prediction of clinical improvement may allow prediction of clinical results after cerebellar stimulation. These techniques have already been used to measure the threshold of stimulation and may allow optimal stimulation characteristics to be assessed. The prolonged neurophysiological effects of stimulation may allow the use of maximum effective intervals between optimal epochs of stimulation so that any cerebellar damage can be minimized.


The reactivity of canine cerebral arteries to O2 and CO2 in vitro. The responses of canine middle cerebral arteries to changes in pCO2 and pO2 were tested in vitro. It was found that there was no response to changes in pCO2 from 38.1 mm. Hg to 26.6 mm. Hg, but there was some constriction of the vessels with lowering of the pCO2 below 26.6 mm. Hg and there was minimal dilatation of the vessels when the pCO2 was increased from 38.1 mm. Hg to 87.2 mm. Hg. There was no response to changes in pO2 from more than 55 mm. Hg to 59.6 mm. Hg, but when pO2 was lowered below 50 mm. Hg there was a sudden, massive constriction of the arteries tested. It is postulated that this constriction is due to build-up of a substance (substances) during a period of hypoxia (pO2 less than 50 mm. Hg). The significance of the results obtained are discussed.


Quebec cooperative study of Friedreich's ataxia: design of the investigation. The general outline of the complete prospective study of 50 cases of spino-cerebellar degeneration is given. The general protocol followed, the criteria for inclusion and the mode of analysis are described. The aim of this study was to establish a base of clinical, physiological and biochemical facts upon which a logical and systematic approach to pathogenesis and treatment of Friedreich's ataxia could be attempted.


Genetic and family studies in Friedreich's ataxia. This study consists of two parts: 1. A detailed genetic analysis of 35 sibships in which 58 individuals were affected with Friedreich's ataxia; and 2. Clinical and laboratory examinations of parents and siblings, in an attempt at carrier detection and diagnosis of the pre-clinical state. The increased parental consanguinity, the lack of affected individuals in other generations, and the lack of significance of extrinsic etiological variables, all suggested an autosomal recessive mode of inheritance, and this was confirmed by formal genetic analyses, employing several different methods. Associated abnormalities in our series of 58 patients included cardiomyopathy (51.7%), diabetes mellitus (19.0%), optic atrophy (5.2%), nerve deafness (5.2%) and congenital malformations (6.9%). The incidence of diabetes mellitus, congenital malformations, and epilepsy and/or febrile convulsions was elevated in first degree relatives of patients with Friedreich's ataxia.


Friedreich's ataxia: preliminary results of some genealogical research. A preliminary genealogical investigation of all the known ancestors from the year 1608 of 4 apparently unrelated French Canadian kindreds with Friedreich's ataxia reveals that the original ataxia gene in the province of Quebec was present within a core of no more than 10 families living in Quebec City in the mid-1600's.


Electroencephalographic findings in Friedreich's ataxia. Electroencephalographic tracings of 50 patients who presented the classical features of Friedreich's ataxia were reviewed. Mild nonspecific abnormalities were found in 33% and consisted of: a) Abnormal slow or irregular background rhythms in 15 patients (30%). b) Intermittent paroxysmal rhythms, considered to be projected from diencephalic or upper midbrain structures, in 4 patients (8%). c) Unilaterally absent driving responses in 2 affected siblings (4%). There was no response to intermittent photic stimulation in 60% of the patients. This finding is not considered a definite abnormality, and its significance remains unclear. Four patients (8%) had epileptic seizures, but of these only two had interictal epileptic abnormalities. There was no correlation between the duration and severity of the disease and the presence of electroencephalographic abnormalities. Friedreich's ataxia is mainly a spinal disorder. Involvement of supraspinal and in particular brain stem or diencephalic structures may be more extensive in those patients who show electrographic abnormalities. This would require confirmation with comparative data based on pathological observations. Impaired function of brain stem inhibitory mechanism may be responsible for the slightly raised incidence of seizures in patients with Friedreich's ataxia and other cerebellar degenerations.


Nerve conduction studies and electromyography in Friedreich's ataxia. Twenty-six of 50 patients were investigated with nerve conduction studies and electromyography using a standard protocol and were compared to the findings in 50 normal control subjects. Almost all cases of typical Friedreich's ataxia had absent sensory action potentials (SAP) in the digital (92%) or sural (96%) nerves. The others had markedly decreased S.A.P's. In these same patients motor conduction velocities were either normal or only slightly decreased. In the second, atypical group of 9 patients, the motor conduction velocities were considerably decreased. Because of the absence of sensory action potentials in Friedreich's ataxia, and that the absence was noted in our very mild cases, it is proposed that this measure be used to facilitate early diagnosis.


Electrocardiographic and vectocardiographic findings in Friedreich's ataxia. Electrocardiographic and vectocardiographic changes are frequent in Friedreich's ataxia. In one of 35 patients both tests were normal. The vectocardiogram is more explicit in demonstrating the severity of the QRS changes with a right ventricular hypertrophy pattern present in 60% of cases. Serial examination of ECG tracings are recommended to monitor the cardiomyopathy in this progressive neurological disorder, in order to detect the onset of congestive heart failure, significant tachyarrythmias, or obstructive cardiomypathy.


Echocardiographic findings in Friedreich's ataxia. Echocardiographic examination of 21 patients with Friedreich's ataxia (age 7 to 28 years) showed cardiac abnormalities in 90% of the cases. They were characterized by varying degrees of septal hypertrophy in 81%, left ventricular free wall hypertrophy in 61%, and a slight reduction of left ventricular internal dimension in 57% of the cases. Asymmetric septal hypertrophy (ASH) with a septal/left ventricular free wall ratio of over 1.3 was found in 29% of the cases, and systolic anterior motion (SAM) of the mitral valve in three patients. Two other patients showed evidence of a different type of cardiomyopathy with marked symmetric left ventricular hypertrophy and marked left ventricular enlargement.


Hemodynamic findings in Friedreich's ataxia. Thirteen patients with classical Friedreich's ataxia underwent cardiac catheterization with recordings of retrograde cardiac pressures, measurements of cardiac output and calculation of the left ventricular volumes and mass. The cardiomyopathy in Friedreich's ataxia falls into the hypertrophic group of cardiomyopathies with decreased compliance of ventricular myocardium, varying degrees of concentric and asymmetric hypertrophy and outflow tract obstruction. Although there is no clear parallel between the degree of abnormal hemodynamic findings and the degree of neurological impairment, severely handicapped patients may present a diffusely hypertrophied and hypokinetic left ventricular myocardium.


Cardiac angiographic findings in Friedreich's ataxia. Angiograms of 12 patients with typical Friedreich's ataxia were analyzed. The results corroborate previous reports and justify the conclusion that the cardiomyopathy is of the hypertrophic type. In 10 of 12 cases, the hypertrophy is concentric, and non obstructive. Less frequently (2 cases), this hypertrophy is accompanied by diffuse hypokinesis and depressed ejection fraction.


Pulmonary function studies in Friedreich's ataxia. Pulmonary function tests were carried out on 20 patients with Friedreich's ataxia. The lung volume, diffusing capacity, flow rate, flow-volume curve, and blood gases were measured. In each patient the degree of scoliosis was measured and the pulmonary function tests were analyzed in relation to the scoliosis. A control group of 13 subjects with idiopathic scoliosis was used for comparison. In both groups, the degree of scoliosis was similar.


Clinical laboratory findings in Friedreich's ataxia. All clinical laboratory tests carried out in 4 groups of patients with the diagnosis of typical or atypical Friedreich's ataxia have been found to be within the normal range. In this prospective study of 50 patients, a number of findings previously reported to be abnormal in the literature, have not been confirmed.


Glucose and insulin metabolism in Friedreich's ataxia. Our prospective survey of 50 ataxic patients confirms the previous finding of frequent clinical or chemical diabetes in Friedreich's ataxia. Eighteen percent of our typical cases have clinical diabetes and 40% at least an abnormal glucose tolerance curve. However, this finding does not appear to be specific to that form of ataxia. Furthermore, we have shown that most patients with ataxia have normal or low fasting insulin levels, but a hyperinsulinic response to a glucose load.


Bilirubin metabolism - preliminary investigation. In our studies, high total bilirubin values in the plasma were noted in cases of Friedreich's ataxia. A bimodal distribution of the values indicated the possible presence of two subgroups of patients. In these kindred, we demonstrated an elevation in unconjugated bilirubin with features similar to those reported in Gilbert's syndrome: normal liver function tests, elevation after fasting and day to day variability. We also report preliminary experiments indicating that bilirubin levels may be taurine dependent. We postulate that the defect could be a secondary component of the ataxic disease, possibly indicating a defect in membrane transport.


Amino acid metabolism in Friedreich's ataxia. A study of amino acids determined by sequential Multi-sample Amino Acid Automatic Analyzer in plasma, urine and cerebrospinal fluid (CSF) in patients with Friedreich's ataxia and control subjects has revealed a number of mathematically significant variations from normal. Of practical physiological importance are the following: a high urinary excretion of alanine with slightly elevated plasma levels; a low plasma and CSF concentration of aspartic acid in the presence of normal urinary values and finally a low CSF concentration of taurine accompanied by normal plasma levels, but elevated urinary output and renal clearance rates. We postulate that the modifications in alanine and aspartic acid are less specific and probably secondary, but there could be a genetic defect in the membrane transport of taurine and the other beta-amino acids in Friedreich's ataxia.


Pyruvate metabolism in Friedreich's ataxia. Friedreich's ataxia patients show evidence of an abnormally elevated and prolonged response of pyruvate and lactate to a glucose load, with normal fasting levels. However, ther is a bimodal distribution of this response with high and low pyruvate responders. This trait appears to be determined genetically, However, although in vivo tests suggest low oxidation of pyruvate, we were unable to confirm any in vitro impairment of each of the components of the pyruvate dehydrogenase (PDH) complex. We conclude that the defect is in the metabolic regulation of PDH, probably at the E3 (lipoamide dehydrogenase) step.


Friedreich's ataxia 1976-an overview.

Friedreich's ataxia 1976-an overview. The prospective investigation of 50 cases of possible Friedreich's ataxia has permitted the clinical and biochemical celineation of the typical disease and an hypothesis on its pathogenesis. A tentative definition of the disorder could read: "Friedreich's ataxia is a progressive degenerative disease always inherited in an autosomal recessive fashion and characterized by a cardiomyopathy and a ganglioneuropathy with dying back phenomenon. It is probably secondary to a defect in the membrane transport of taurine and beta-alanine and/or a defect in the regulation of pyruvate oxidation." The existence of two pathogenetically distinct distinct entities with the same phenotype is a strong possibility.


Graphic monitoring of labour.

Graphic monitoring of labour. The parturograph is a composite record designed for the monitoring of fetal and maternal well-being and the progress of labour. It permits the early recognition of abnormalities and pinpoints the patients who would benefit most from intervention. Observations are made from the time of admission of the mother to the caseroom and recorded graphically. Factors assessed include fetal heart rate, maternal vital signs and urine, cervical dilatation, descent of the presenting fetal part, and frequency, duration and intensity of uterine contractions.


Physicians' response to abnormal results of routine urinalysis. To determine the clinical usefulness of routine urinalysis, the records of 400 patients were examined for results of the first urinalysis following admission to hospital, and the attending physician's response to abnormal findings was evaluated. Results were abnormal for 116 patients (29.0%); there were 22 (5.5% of total urinalyses) abnormalities of chemical constituents (protein, glucose or bilirubin was present) only, 56 (14.0%) of sediment only and 38 (9.5%) of both chemical constituents and sediment. The attending physician did not respond to abnormal results in 50.9% of the 116 instances.


Urethral response to latex and Silastic catheters. The reaction of the urethral mucosa to latex and Silastic catheters was compared in two groups of patients undergoing prostatectomy. The bacteriologic response in the two groups differed little; however, Silastic catheters produced less cellular reaction than latex catheters.


Treatment of cutaneous ulcers with benzoyl peroxide. Benzoyl peroxide, a powerful organic oxidizing agent, was applied topically according to a carefully developed technique to cutaneous ulcers of different types. The healing time was shortened greatly by the rapid development of healthy granulation tissue and the quick ingrowth of epithelium. Exceptionally large pressure ulcers with deep cavities, undercut edges and sinus tracts were sucessfully treated, as were stasis ulcers of long duration resistant to all other therapy. There were only 13 treatment failures among the 133 cases. The slow, sustained release of oxygen by benzoyl peroxide was though to be responsible for the success. The only complications were contact irritant dermatitis in 3% and contact allergic dermatitis in 2% of patients treated.


Effects of long-term administration of clonidine on plasma renin activity. Plasma renin activity (PRA) was studied before and during long-term treatment with moderate oral doses (0.2 or 0.3 mg/d) of clonidine. Nine outpatients with essential hypertension received clonidine for 12 weeks; a significant decrease in blood pressure was evident in all patients. Except for a nonsignificant increase after 12 weeks of treatment, PRA values were not notably changed by clonidine therapy. No correlation was found between individual blood pressure changes and PRA variation during the study. The absence of a net effect on PRA in this study does not exclude more complex interactions of clonidine with the renin-angiotensin system. Nonetheless, clonidine cannot generally be classified as a "renin-inhibiting" drug.


Right-sided endocarditis and ventricular septal defect. Right-sided endocarditis occurred in a 40-year-old woman with ventricular septal defect. This association is uncommon in adults. Because of the changing and variable clinical patterns of this disease, it is difficult to make a prompt diagnosis. In this case diagnosis was delayed for almost a year. The occurrence of pneumonia due to Streptococcus viridans was the most important extracardiac manifestation.


Systemic infection with Alaria americana (Trematoda). Alaria americana is a trematode, the adult of which is found in mammalian carnivores. The first case of disseminated human infection by the mesocercarial stage of this worm occurred in a 24-year-old man. The infection possibly was acquired by the eating of inadequately cooked frogs, which are intermediate hosts of the worm. The diagnosis was made during life by lung biopsy and confirmed at autopsy. The mesocercariae were present in the stomach wall, lymph nodes, liver, myocardium, pancreas and surrounding adipose tissue, spleen, kidney, lungs, brain and spinal cord. There was no host reaction to the parasites. Granulomas were present in the stomach wall, lymph nodes and liver, but the worms were not identified in them. Hypersensitivity vasculitis and a bleeding diathesis due to disseminated intravascular coagulation and a circulating anticoagulant caused his death 8 days after the onset of his illness.


Traumatic vasospastic disease in chain-saw operators. Raynaud's phenomenon is commonly induced in chain-saw operators by vibration; the hand guiding the tool is the more severely affected. The condition tends to persist after use of the chain-saw is stopped but compensation is rarely sought. Among 17 cases of Raynaud's phenomenon in lumberjacks the condition was found to be related to use of the chain-saw in 14, 10 of whom had to give up their work in colder weather because the disease was so disabling. Two criteria essential to establish the condition as vibration-induced Raynaud's phenomenon are the presence of symptoms for at least 2 years and a history of at least 1 year's constant use of the chain-saw. Careful physical examination and simple tests of vascular function will provide objective evidence of permanent damage by which the patients may be classified and compensated.


Perforation of the gallbladder: analysis of 19 cases. Perforation of the gallbladder occurred in 19 (3.8%) of 496 patients with acute cholecystitis treated at one hospital in an 8-year period. The average age of the 19 patients was 69 years and the female:male ratio was 3:2. Most had a history suggestive of gallbladder disease and most had coexisting cardiac, pulmonary, renal, nutritional or metabolic disease. The duration of the present illness was short, perforation occurring within 72 hours of the onset of symptoms in half the patients; the diagnosis was not suspected preoperatively in any. In the elderly patient with acute cholecystitis who has a long history of gallbladder disease, cholecystectomy should be performed early, before gangrene and perforation of the gallbladder can occur.


Clindamycin plus gentamicin as expectant therapy for presumed mixed infections. The prevalence of obligate anaerobes was studied prospectively in 60 patients with severe sepsis of intra-abdominal, soft tissue, female genital or oropulmonary origin. In addition, the efficacy of clindamycin (for anaerobes) plus gentamicin (for aerobic bacteria, especially coliforms) as initial empiric therapy in these patients was evaluated. Among 54 patients with cultural proof of infection, anaerobic pathogens were recovered from 52%. Nineteen patients had bacteremia; Bacteroides fragilis and Klebsiella pneumoniae were the most prevalent pathogens, being isolated in five patients each. Infection was eradicated in 56 of the 60 patients (93%). Mortality related to sepsis was 7% in the entire group, 16% in patients with bacteremia and 2% in patients without bacteremia. Eighty-five percent of aerobic isolates tested were susceptible in vitro to either gentamicin or clindamycin; 97% of anaerobic isolates were inhibited by 5 mug/ml of clindamycin.


Patterns of local and tourist use of an emergency department. Illness patterns of local and tourist patients in an emergency department of a medium-sized Ontario city with a single hospital were compared. Frequencies of specific and broad categories of ailments and rates of admission to the hospital were similar in the two groups. However, non-Canadian tourists were admitted to hospital at a much lower rate than Canadian tourists. Rates of visits to the emergency department within certain age categories were remarkably similar, as were rates within the sexes. It is concluded that, in view of the striking similarity in the illness pattern of a group of patients not professionally referred to the hospital and that of local patients, who have potential contact with a more extensive medical network, public attitudes, rather than availability of health professionals, determine the pattern of illness observed in an emergency department.


The effect of cytosine arabinoside on platelet aggregation. Platelet aggregation induced by ADP, collagen, epinephrine, and thrombin was studied in patients with acute leukemia in complete remission, before and after a continuous 5-day intravenous infusion of cytosine arabinoside at a dose of 100 mg/m2 per day. Aggregation was also measured in normal subjects with cytosine arabinoside added in vitro. Cytosine arabinoside had no significant effect on platelet aggregation after either in vitro or in vivo administration.


Radiation therapy of malignant melanoma: experience with high individual treatment doses. Reports of the existence of a large shoulder on the radiation survival curve of cultured mouse and human malignant melanoma cells prompted a clinical trial of radiation therapy using high individual-dose-fractionation schedules. Typically, individual doses of larger than or equal to 600 rads were delivered once or twice weekly. The most clear-cut effect was against skin metastases. Twenty-nine of 33 lesions showed partial or complete regression when treated in this manner. None of 11 lesions responded that were treated with individual treatment doses of 200 to 500 rads, although in some cases the total doses were greater than 5000 rads. Some of the possible roles for an effective radiation regimen in the overall management of this complex disease are discussed.


Total-body sequential segmental irradiation and combination chemotherapy for children with disseminated neuroblastoma. Fourteen children with disseminated neuroblastoma were treated with segmental total-body irradiation and a combination of cyclophosphamide, vincristine and Adriamycin. Six others had localized tumors and were treated with either surgery alone or limited irradiation and chemotherapy. The main objective of the study was to find out if this aggressive therapy for disseminated neuroblastoma would be tolerated and would promote longer disease-free remissions and possibly, cures. Complete responses were obtained in all patients with localized tumors. Of the 14 patients with disseminated disease, three had complete responses, five had partial responses, two had objective responses, and four were classified as nonresponders. Survival rates for this group are poor. Only two patients are still alive, and the single patient who survives free of disease has had a complex clinical course that is only indirectly a result of treatment. The median survival for patients with disseminated tumor was 9 months, not appreciably different from earlier result. Although toxicity was clinically manageable, it interfered with the planned schedule of therapy. Continuous weight loss combined with severe bone marrow suppression due to irradiation prevented about 50% of the scheduled drug dose from being administered. This resulted in poor control of tumor outside of radiation ports and eventually led to progressive disease within previously irradiated sites. We conclude that irradiation used in this manner will not improve disease-free survival of children with disseminated neuroblastoma. It is essential that disseminated disease be controlled before extensive irradiation is attempted.


Immunocompetent cells in patients with malignant disease. I. The lack of naturally occurring killer cell activity in the unfractionated circulating lymphocytes from patients with chronic lymphocytic leukemia (CLL). The unfractionated, buffy coat cells of patients with chronic lymphocytic leukemia (CLL) were compared with their counterpart cells from normal volunteers for the capacity to lyse chromium-labeled xenogeneic target cells in vitro. Whereas killer cells were consistently detected in the circulation of normal individuals, no significant numbers of killer cells could be detected in the circulation of CLL patients. It is concluded that either these cells are not present in the circulation of CLL patients or that they are present in small numbers undetectable by this procedure. The possibility that killer cells in CLL patients are diluted by the much larger number of immunoincompetent cells has been ruled out.


Infusion hepatic angiography in diagnosis of liver metastases. Infusion hepatic angiography was used, together with conventional angiography, for diagnosis in 68 patients with liver metastases. The combination of both techniques led to a diagnostic accuracy of 97%. Metastases were missed in only two patients, both of whom had underlying liver or biliary disease. In a comparison of the two techniques, the infusion study was found diagnostically essential in five patients (7%) and afforded improved diagnosis in 49 others (72%). In 10 patients (15%), it gave equivalent information; and in four patients (6%) less information than the conventional technique. Infusion hepatic angiography is a useful complementary technique in antatomic liver diagnosis, especially in its ability to improve upon the diagnostic accuracy of the capillary phase of hepatic angiography.


Assessment of serial carcinoembryonic antigen (CEA) assays in postoperative detection of recurrent colorectal cancer. Monthly serial postoperative CEA determinations, three-monthly system review plus physical examination, and a battery of six-monthly laboratory and radiologic tests were compared in order to evaluate each in detection of recurrent colorectal cancer. Twelve of the 33 patients studied prospectively developed recurrent disease. In this study CEA was found not to be a substitute for careful clinical follow-up, but if used in a serial manner it was a useful adjunct for detection of early recurrent cancer, especially intra-hepatic and retroperitoneal disease recurring in patients with elevated pretreatment CEA levels. The other laboratory and radiologic tests employed were often useful to confirm progressing disease, but they did not reveal any first evidence of recurrent disease.


Pulmonary lymphangiomyomatosis: three new cases studied with electron microscopy. Three cases of pulmonary lymphangiomyomatosis are described, with emphasis on the ultrastructural changes. The clinicopathologic features corresponded to those previously described. Each patient was a female in the reproductive years; breathlessness and recurrent pneumothoraces were the predominant clinical features. Histologically, the lungs showed a focal interstitial infiltrate of short, spindle-shaped mononuclear cells compatible with primitive smooth muscle, which was associated with irregular emphysema and hemosiderosis. Electron microscopy confirmed the smooth muscle nature of the pulmonary infiltrate and showed the presence of cells intermediate between smooth muscle and fibroblasts. Abnormalities were also noted in the pulmonary connective tissue that are possibly related to the fragility of the lung in this condition.


Nodular fasciitis, a lesion of myofibroblasts: an ultrastructural study. Eight histologically typical cases of nodular fasciitis were studied by electron microscopy and histochemistry. The findings confirm accepted views of the morphology of this lesion, and also reveal the previously undescribed fact that nodular fasciitis is a lesion of myofibroblasts. Its cells have the basic ultrastructural features of fibroblasts. In addition, all cells contain peripheral, longitudinally oriented bundles of myofilaments and hemidesmosome-like structures with associated basement membrane-like material. Many cells have deeply clefted nuclei, desmosomes, and pinocylotic vesicles. These specialized features are identical to thos of the myofibroblasts that have been described ifibroblasts have been found in inflammatory and trauma-related conditions and not in most studies of fibroblastic neoplasms. However, additional studies of proliferative and neoplastic fibroblastic lesions are needed to clarify the distribution and significance of myofibroblasts.


The role of bone marrow aspiration and biopsy in detecting marrow involvement by nonhematologic malignancies. A review of the records of the Memorial Sloan-Kettering Cancer Center identified 291 adult patients with nonhematologic malignancies who had undergone simultaneous bone marrow aspiration and biopsy from the same anatomic site. In 236 cases both samples were negative for tumor whereas in 39 both were positive. The biopsy was positive in three patients with a negative aspirate whereas in three others to aspirate was positive with a negative biopsy. The higher rate of tumor detection on aspirate in comparison with previous reports may be due to a thorough initial screening provided by technologists. Both aspiration and biopsy appear to be indicated for full evaluation of bone marrow in cancer patients.


Histologic criteria for the diagnosis of superficial spreading malignant melanoma: formulated on the basis of proven metastatic lesions. Histologic material was studied from 30 patients with metastasizing cutaneous superficial spreading malignant melanoma in an attempt to establish reproducible criteria for the accurate diagnosis of the disease. This paper details the criteria for the histologic diagnosis of primary superficial spreading malignant melanoma of the skin.


Sertoli cell tumors of ovary: light microscopic and ultrastructural study with histogenetic considerations. Two cases of pure Sertoli cell tumors of the ovary are presented. The tumors were grey to brown and generally solid, but with several cystic areas. They showed a highly differentiated, but variable, histologic patterns with solid cords of neoplastic cells, as well as tubular formations. Ultrastructurally, the basal part of the cells rested on a nonfibrillary basement membrane layer while the free border showed occasional cilia. Laterally, the cells showed tight junctions and desmosomes. Abundant rough endoplasmic reticulum and some cystically dilated smooth endoplasmic reticulum were evident. The theories regarding the histogenesis are discussed. Enough similarities, both by light and by electron microscopy, are presented between these tumors and the Sertoli cell to justify classifying these ovarian tumors as Sertoli cell in type. The development of cilia is considered to be a manifestation of focal metaplasia of the neoplastic Sertoli cell.


Carcinoembryonic antigen (CEA) activity in pancreatic juice of patients with pancreatic carcinoma and pancreatitis. Carcinoembryonic antigen (CEA) activity was assayed in plasma and in pure pancreatic juice from eight patients with carcinoma of the pancreas, 28 patients with pancreatitis, and 13 controls with no demonstrable pancreatic disease. Juice specimens were obtained via direct transduodenal cannulation of the pancreatic duct. The mean pancreatic juice CEA activities in controls, pancreatitis, and pancreatic carcinoma were 8.1 ng/ml, 18.6 ng/ml, and 309 ng/ml, respectively. Pancreatic juice CEA activity in patients with cancer of that organ was significantly higher than in those with pancreatitis or in controls. None of the 32 subjects with both pancreatic juice CEA activity less than 30 ng/ml and plasma CEA less than 2.5 ng/ml had pancreatic cancer. Three of the four patients with CEA elevations in both fluids above these levels harbored this malignancy. These findings suggest that combined measurement of CEA activity in plasma and pancreatic juice may help in diagnosing pancreatic disease.


Salivary gland tumors in atomic bomb survivors, Hiroshima, Japan. I. Epidemiologic observations. An epidemiologic investigation was undertaken in Hiroshima to study the relationship of salivary gland tumors to exposure to ionizing radiation. Two hundred and eleven cases examined between 1953-1971 were confirmed by a review of histologic specimens. Of these, 66 cases occurred in residents of Hiroshima City who were born before the A-bomb: 30 among A-bomb-exposed, and 36 in non-exposed individuals. The incidence of salivary gland tumors among the exposed individuals was significantly higher, 2.6 times greater than that among the nonexposed individuals for all tumors, and 10 times greater for malignant tumors. The incidence increased with proximity to the hypocenter for the directly exposed. An increased incidence was also found among early entrants, particularly those entering the city within 3 days of the A-bomb.


Papillary renal cell carcinoma: a clinical, radiologic, and pathologic study of 34 cases. Papillary renal cell carcinoma (RCC) is known by its tendency to avascularity by angiography; however, data concerning its clinicopathologic spectrum and prognosis are not available. In a review of 224 renal cell carcinomas accesioned in our files, 34 were found to be papillary and 190 of other histologic types. A comparative analysis of these two gropus revealed marked differences. The majority of papillary tumors (85.3%) were in pathologic stage I, whereas more than half of the nonpapillary tumors had extended beyond the limits of the kidney. Follow-up data revealed that the survival for papillary RCC was significantly higher than that for nonpapillary tumors. This difference held true even when tumors in the same pathologic stage were compared. Many papillary tumors, particularly those with a favorable course, were massively necrotic, densely infiltrated by macrophages, or both. In view of these findings, the possibility that host mechanisms are involved in destruction and confinement of the tumor is discussed. Examination of kidney tissue distant from the tumor disclosed, in some cases, atypical hyperplastic changes of collecting tubules; this raises the possibility that some papillary tumors arise from distal tubular epithelium. Hypo- or avascularity was present in all papillary RCC's studied by angiography.


Endodermal sinus tumor of the pineal region: case report. This is a case report of an endodermal sinus tumor occurring in the pineal region of a 12-year-old Caucasian boy. Germ cell tumors of this type demonstrate a selective overgrowth of yolk sac endoderm associated with extraembryonic mesoblast and arise perferentially in the gonads of young children. This is the ninth known report of this tumor in the world literature. Its occurrence in the posterior third ventricle again confirms that pineal region germ cell tumors are histologically analogous to germ cell tumors originating in the gonads. A disturbance in the region of the primitive streak is thought to account for the exclusive midline location of this tumor in extragonadal sites. This patient was treated with a combination of vincristine, actinomycin D, and cyclophosphamide, and concomitant cobalt irradiation. For endodermal sinus tumors in the pineal region, this combination appears more effective than previously reported treatment by irradiation alone.


Olfactory neuroblastomas: a clinicopathologic study. Clinical and pathologic findings in seven patients with olfactory neuroblastomas are reviewed. Thes neoplasms occurred over a wide age range and, regardless of microscopic pattern, had an unpredictable clinical course. Total extirpation followed by radiation provided optimal therapeutic benefit. The difficulty of pathologic diagnosis of olfactory neuroblastomas is emphasized by the number of neoplasms excluded from this series after critical review of clinical and microscopic findings.


Epithelial papilloma and squamous cell carcinoma of the nasal cavity and paranasal sinuses: a clinicopathological study. Seventeen cases of intranasal epithelial tumors are reviewed. Thirteen were epithelial papillomas and four were squamous cell carcinomas associated with epithelial papillomas. In two cases followed over a 10 year period, transformation from an initial papilloma into a carcinoma was demonstrated. The histopathologic caracteristics of these lesions are described including the presence of prominent palisading and intraepithelial nesting in some tumors. The literature was reviewed for reports of carcinoma arising in previously benign epithelial papillomas. We suggest that squamous cell carcinoma may occasionally arise from a previously benign epithelial papilloma.


Excess and deficit lung cancer mortality in three ethnic groups in Texas. Based on Texas vital statistics for 1969-71, patterns of lung cancer mortality in three ethnic groups are examined. Among males, the risk of lung cancer for Mexican Americans is considerably lower than for Blacks and Anglos for ages under 75 and slightly higher for older ages. Among females, Mexican American exhibit a distinct excess of lung cancer mortality for ages 70 and over and a deficit for younger ages. The excess among Mexican American females is confined mainly to the older foreign-born women and the excess is reduced for ages 45-60 and diminishes for younger immigrants. This suggests that the excess risk among Mexican Americans will completely disappear within a generation and a general deficit pattern will emerge for all ages. The implications of the diminishing excess and the emerging deficit lung cancer mortality among Mexican Americans clearly call for further study in exploring the effect of cultural change on mortality patterns, particularly for cancer.


Surgical treatment of solitary pulmonary metastasis. Seventeen patients undergoing pulmonary excision for metastatic tumors of the lung from 1965 to 1975 are reviewed with an overall four-year survival of 72%. From this group, four patients are alive five years and more after operation. In two patients however, multiple metastases in the contralateral lung and bones have appeared. One of them underwent a second removal of metastatic tumor in the other lung. On the basis of this limited experience and the one reported in the literature, we believe that excision of pulmonary metastasis in selected cases improve the prognosis of those patients, prolong life, and in some cases may even result in cure of the basic disease.


Early morning hydroxyproline excretion in patients with breast cancer. The hydroxyproline/creatinine excretion ratios have been measured in half-hour fasting morning urine specimens from breast cancer patients and compared with corresponding values measured in 24 hour urine collections. Both parameters show a close correlation. The value of the half-hour test in predicting the presence of early bone metastases, in monitoring the response of patients to therapy and in eliminating unwanted effects of dietary Hydroxyproline intake are discussed.