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Biomedical subjects

J J Welsh

Publications and source records attributed to J J Welsh.

At least 37 records · Page 2Linked to original sources

Internal anatomy of the larynx and the spread of cancer.

This project investigated the potential spread of cancer within the larynx by an analysis of the permeability and resistance of the subepithelial spaces. Permeation and diffusion of dye injections in the loose connective tissues below the epithelium was analyzed by histologic preparations in the sagittal plane. The margins of the infusion were identified grossly and microscopically, and the influence of the fibrous, elastic, and muscular components was analyzed with reference to the dispersion of the dyes. A close correlation between laboratory data from normal postmortem larynges and clinical problems of laryngeal cancer was observed in this study.

Adult↗

Endoscopic problems due to cervical vertebral diseases.

The authors draw attention to cervical spine disorders that limit mobility of the vertebrae and thereby interfere with esophagoscopy. Four orthopedic disorders that either fuse the cervical spine or produce massive osteophytes are discussed and exemplified by specific cases, and appropriate techniques for endoscopy are recommended.

Aged↗

Study of the teratogenic potential of FD&C Red No. 40 when given in drinking water.

FD&C Red No. 40 in the drinking water at a level of 0, 0.2, 0.4, or 0.7% was available ad libitum to female Osborne-Mendel rats throughout gestation. The treated females consumed 273.6, 545.7, and 939.3 mg FD&C Red No. 40 per kg body weight per day, respectively, for the three dose levels. The animals were sacrificed on gestation day 20. No fetal terata were seen. There were no dose-related changes in maternal findings, number of fetuses, fetal viability, or external or visceral variations. Skeletal development appeared similar to that of the control animals with the exception of the incidence of fetuses with reduced ossification of the hyoid, which was increased significantly at the 0.7% dose level. A dose-related increase occurred in the number of litters containing fetuses with at least two skeletal variations, but the numbers of litters with fetuses with at least one and at least three variations were not different from control values.

Abnormalities, Drug-Induced↗

Adaptation to low dietary calcium in magnesium-deficient rats.

To determine if adaptation to low calcium (Ca) diets is impaired by magnesium (Mg) deficiency, weanling rats were pair-fed control (700 mg Mg/kg diet) or low Mg (70 mg Mg/kg diet) diets containing 5000 mg Ca/g diet for 7 or 10 d. Half of the animals from each group were then killed; the remainder continued on their previous Mg intakes and were subjected to low (500 mg Ca/kg diet) dietary Ca for 7 or 15 d. After 10 d of Mg deficiency, rats fed adequate Ca were hypomagnesemic and hypercalcemic, relative to controls, and had elevated circulating parathyroid hormone (PTH) but normal 1,25-dihydroxycholecalciferol (1,25-DHCC). After 7 d of low dietary Ca, there were no significant differences in plasma Ca, 1,25-DHCC or PTH between control and Mg-deficient rats despite a 50% reduction in plasma Mg in the latter group. After 15 d of low Ca stress, control rats remained normocalcemic, but Mg-deficient rats developed relative hypocalcemia despite similar, high circulating levels of PTH. Plasma 1,25-DHCC in the hypocalcemic, Mg-deficient rats was significantly lower than that of control rats also exposed to low dietary Ca, suggesting an impairment in 1,25-DHCC production during chronic Mg depletion. Significantly elevated renal Ca content was present in the Mg-deficient rats, which was unrelated to dietary Ca and preceded the development of hypocalcemia. The results indicate that both the duration of Mg deficiency and the Ca content of the experimental diet are important determinants of an animal's ability to maintain Ca homeostasis during Mg depletion.

Adaptation, Physiological↗

Potential reversibility of skeletal effects in rats exposed in utero to caffeine.

Groups of Osborne-Mendel rats, killed at three time intervals following mating, were studied to determine whether prenatal skeletal ossification delays observed following low-level caffeine administration represent transient or persistent ossification problems. Group A litters were killed on gestation day 20; group B neonates were killed on post-natal day 0; and group C pups were killed on post-natal day 6. Within each group, dose levels of 0, 0.018, 0.036 or 0.07% caffeine in distilled water were available ad lib. to groups of 30-60 dams from gestation day 0 to day 20. Average daily caffeine consumption was 24.7-29.0 mg/kg body weight for the 0.018% group, 42.7-48.8 mg/kg body weight for the 0.036% group and 70.6-75.1 mg/kg body weight for the 0.07% group. In group A litters, the mean number of viable foetuses was significantly less in the mid-dose and high-dose animals than in the controls. In the same group, the average number of foetuses per litter with at least one sternebral ossification delay was increased significantly in all treated groups and the average number of foetuses per litter with at least two sternebral variations was significantly increased in the mid- and high-dose groups. The percentages of litters containing foetuses with at least two and at least three sternebral variations and the average number of foetuses per litter with at least three sternebral variations were significantly increased only in the high-dose group. Foetuses from the mid- and high-dose groups also had significant increases in certain skeletal defects, namely missing centra and reduced ossification of the dorsal arch. Foetuses from the high-dose group also had significant increases in bipartite supraoccipital, and reduced ossification of the hyoid, metacarpals and metatarsals. In group B, day 0 neonates from all treated groups showed a significantly increased incidence of delayed sternebral ossification (average number of foetuses per litter with one or more missing, incomplete or bipartite sternebrae). The percentages of litters containing neonates with delayed sternebral ossification were also increased significantly in all treated groups. Neonates from the 0.07% level in group B also exhibited a significant increase in the incidence of supernumerary rib bud, and in reduced ossification of the metacarpals, metatarsals and calcaneus bones. Significant increases were also seen, in group B, in the low- and mid-dose animals, respectively, in supernumery rib bud and in reduced ossification of the metatarsals.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗

Teratogenic potential of purified pentachlorophenol and pentachloroanisole in subchronically exposed Sprague-Dawley rats.

Male and female Sprague-Dawley (Spartan) rats were exposed to dietary levels of 0, 60, 200 or 600 ppm purified pentachlorophenol (PCP) or pentachloroanisole (PCA) for 181 days, through mating and pregnancy. The daily intakes of PCP were 0, 4, 13 or 43 mg/kg body weight and of PCA were 0, 4, 12 or 41 mg/kg body weight. Animals exposed to PCP generally consumed more food than control animals during pregnancy. Dams at the high-dose level of both compounds showed evidence of toxicity, weighing less on day 0 of gestation and gaining less throughout pregnancy than did the controls. Dams exposed to the high dose of PCP gained less weight during pregnancy (exclusive of the gravid uterus) than control dams. At the 43 mg/kg/day dose level PCP was embryolethal. Foetuses at the lower dose levels of PCP exhibited dose-related decreases in body weights. A reduction in crown-rump length and an increase in foetal skeletal variations were seen at 13 mg/kg/day in PCP animals only. An intake of 41 mg PCA/kg/day was associated with a decrease in the number of corpora lutea and in embryolethality. PCA exposure also resulted in reductions in foetal body weight and crown-rump lengths of males at 4 and 41 mg/kg/day. Female foetuses were unaffected.

Abnormalities, Drug-Induced↗

Study of the teratogenic potential of guar gum.

Guar gum in the diet at 0, 1, 2, 4, 7.5 or 15% was available ad lib. to male and female Osborne-Mendel rats for 13 wk before mating, during mating and throughout gestation. During gestation, the females consumed 0, 0.7, 1.4, 2.7, 5.2 or 11.8 g guar gum/kg of body weight/day, respectively. The animals were killed on gestation day 20. No behavioural effects were seen in any of the treated dams, and no females died during the experiment. Pregnant females in the treated groups consumed less food than the controls during gestation days 0-20 but the decrease was significant only in the 4 and 7.5% groups and was not dose related. Ingestion of guar gum before mating did not affect fertility. In the dams fed 1-7.5% guar gum, there was no effect on the number of corpora lutea or implantations. The dams fed 15% guar gum had slightly fewer corpora lutea and implantations than the controls but no effect was seen on implantation efficiency in this group. The number of viable foetuses/litter was also reduced slightly but not significantly in the 15% group, but since the number of resorptions was not affected, this decrease appears to be an effect of the decreased number of corpora lutea. There was no compound-related effect on foetal development or sex distribution. No terata were seen.

Abnormalities, Drug-Induced↗

Study of the teratogenic potential of gum arabic.

Gum arabic in the diet at 0, 1, 2, 4, 7.5 or 15% was available ad lib. to male and female Osborne-Mendel rats during premating and mating and throughout gestation. During gestation, the treated females consumed from 683 mg gum/kg body weight/day in the 1% group to 10,647 mg gum/kg/day in the 15% group. The animals were killed on gestation day 20. There were no dose-related changes in maternal findings, number of foetuses, foetal viability or external, visceral or skeletal variations. No terata were seen.

Abnormalities, Drug-Induced↗

Teratogenic potential of triphenyl phosphate in Sprague-Dawley (Spartan) rats.

Male and female Sprague-Dawley (Spartan) rats were fed dietary levels of 0, 0.25, 0.50, 0.75 or 1.00% triphenyl phosphate (TPP) from 4 weeks post weaning for 91 days, through mating and gestation. At these dietary levels, the daily intake of TPP during pregnancy was 0, 166, 341, 516 and 690 mg/kg body weight, respectively. TPP exposure had no toxic effects on mothers or offspring at these dosages. The types of developmental anomalies were similar in both treated and control animals. No significant increases in the incidence of anomalies were seen in the treated groups as compared to control values. TPP was not teratogenic in Sprague-Dawley rats at the levels tested.

Animals↗

Teratological research using in vitro systems. IV. Cells in culture.

Several in vitro cellular systems designed to screen agents for teratogenic potential are described in this report. These assays were selected from a review of literature published through the spring of 1986 that generated over 100 references on teratological research using cell-based systems. Some of the assays have a broader application than others, but most require confirmation by one or more additional complementary tests because of the specificity of the teratogenic mechanism the assays are investigating. Included are systems that use analysis of tumor cell attachment; intercellular communication; growth of human embryonic palatal mesenchyme cells; progesterone production in porcine granulosa cells; differentiation of embryonic neural crest, limb bud, midbrain, and Drosophila cells; and differentiation of tumor cells. Because of the dynamic nature of cell culture work, the group of assays listed here should not be viewed as encompassing all cell systems of value with regard to teratogenicity testing; instead, the list represents several of the more prominent systems now being evaluated by the scientific community.

Animals↗

Reproduction study of caffeine administration to male Osborne-Mendel rats.

The potential for caffeine, administered twice daily by gavage in a total dose of 40 or 80 mg/kg/day, to adversely affect the reproductive performance of male rats was investigated. Treatment was continued through 3 wk of serial mating; mating and dosing were terminated concurrently, after which the sires were autopsied and their testes weighed. Controls were treated similarly with distilled water. Significant dose-related differences were detected for sire body weight, but not for testes weight. The majority of the significant effects on the offspring were for those born to the low-dose sires. Statistically significant differences were sporadically detected for the number of pups born and their body weights and survival; however, these differences were not consistently detected in either a dose- or temporal-related fashion. Thus, caffeine appears to have little potential to produce adverse reproductive effects when administered by gavage to male rats at the levels tested in this study.

Administration, Oral↗

Metabolic effects of dietary manganese supplementation in ob/ob mice.

When fed a manganese-sufficient (20 ppm) diet, obese (ob/ob) mice have reduced levels of Mn in liver and brown adipose tissue (BAT), and depressed activities of succinate dehydrogenase (SDH) and manganese-containing superoxide dismutase (MnSOD) in BAT, compared to lean mice. Dietary Mn supplementation (200 ppm Mn) increased the Mn concentration in BAT in lean and obese mice and the Mn content of liver in the ob/ob mouse. Mn supplementation also led to an increase in the specific activities of SDH and MnSOD in BAT of lean and obese mice. In the obese mouse, these changes were paralleled by changes in the histological appearance of the tissue. The results indicate that the metabolism of Mn is altered in the liver and BAT of ob/ob mice, and that these alterations are responsive to dietary Mn supplementation.

Adipose Tissue, Brown↗

Central presbycusis.

The phenomenon of central presbycusis has been investigated employing a central auditory battery in elderly individuals with essentially normal hearing. The studies indicate a progressive loss in central auditory competence measured by simultaneous binaural challenges and frequency and temporal distortion tests. The rate of failure is related to age, on the whole, but there is increasing variability from the normals with seniority. The hearing disability in noise or speech competitive environments is explained by these data. Auditory disabilities related to poor articulation and rapid speech presentation are identified by other tests in the battery. Central presbycusis, in addition to the peripheral form, does exist and further compounds the hearing disorder in many elderly.

Age Factors↗

Magnesium absorption in human subjects from leafy vegetables, intrinsically labeled with stable 26Mg.

Collards, turnip greens, leaf lettuce, and spinach, grown in nutrient solution so that their Mg content was 80 to 90% 26Mg, were tested in ambulant male volunteers stabilized on a constant metabolic diet. The freeze-dried vegetables were incorporated in bran muffins in which the vegetables replaced part of the bran. Bran muffins without vegetables were consumed for breakfast each day. They were also used as a standard test meal to which the vegetable muffins were compared. All subjects participated in three consecutive isotope absorption tests: one of the standard test meal and two of the vegetables. The standard test was carried out after at least 30 days on the controlled diet. Subsequent tests of vegetables followed at 4-wk intervals. Each test meal contained 30 microCi 28MgCl2 and 50 mg stable 26Mg, the latter either as the intrinsic label of a test vegetable or as 26MgCl2 in solution taken with the standard bran muffins. Net absorption of both isotopes was measured to establish exchangeability and to determine relative Mg absorption from the vegetables. Exchangeability was 90% or higher from all meals tested. Relative Mg absorption was highest from collards and least from the standard test meal. Net absorption values ranged from 40 to 60%.

Feces↗

A study of the teratogenic potential of caffeine ingested in drinking-water.

Caffeine dissolved in drinking-water was available ad lib. to Osborne-Mendel rats at dose levels of 0, 0.007, 0.018, 0.036, 0.07, 0.10, 0.15 or 0.20% during days 0-20 of gestation. The corresponding daily caffeine intakes were 0, 10.1, 27.4, 50.7, 86.6, 115.8, 160.9 and 204.5 mg/kg body weight. Dosages of 160.9 and 204.5 mg/kg were associated with decreased implantation efficiency, increased resorptions and decreased mean numbers of viable foetuses. Numbers of runts were significantly increased after dosages of 115.8-204.5 mg/kg/day. Foetal body weight and length were decreased and oedematous foetuses were increased at dosages of 86.6-204.5 mg/kg/day. Contrary to results seen after gavage studies, caffeine available ad lib. in drinking-water produced no dose-related gross anomalies. Only two animals with missing or hypoplastic nails were produced, both in the 160.9-mg/kg group. Sternebral ossification deficiencies were increased at all dose levels except 10.1 mg/kg/day. Skeletal ossification deficiencies were increased in a dose-related manner at the four highest dose levels. Caffeine given by water bottle produced ossification deficiencies similar to those seen after intubation, but at higher dosages.

Animals↗

Effect of sound deprivation on central hearing.

The authors have investigated the thesis that intermittent hearing impairment due to middle ear disease in the early years of life results in a central auditory disturbance which may persist in adulthood. The concept that, during the speech development years, auditory disturbances interfere with the normal maturation of central auditory processing appear to be clearly established. Thirty-five children, free of active ear disease and normally hearing by standard peripheral audiometry, are the basis for the study. The monotic tests employing temporal and frequency distortion and the dichotic challenges of competing stimuli and central integration provide the test data. Approximately 75% of the study group fail at least 1 segment of the battery, beyond 2 standard deviations from the normal data. A decreasing percentage of the study group exceed the normative values in 2 or more of the test components. In view of these data on aggressive program of auditory conservation is suggested during the early years of life.

Auditory Perceptual Disorders↗

Central auditory testing and dyslexia.

A group of dyslexic pupils with normal end organ function was studied by a central auditory battery to determine whether a hearing disability existed. The clinical features of dyslexia are presented with emphasis on the psychological developmental and functional disorders associated with this reading problem. The central battery of Willeford was selected as the test medium and the results of the 77 dyslexic students were compared to the normative data. The model proposed by Sparks, et al., is accepted as the mechanism for dichotic audition. Reference is made to the organic basis of reading disorders from lesion in the calcarine area to the angular gyrus. The competing sentence test, binaural fusion, rapidly alternating speech perception, and filtered speech are described in detail and are organic foundation for the study. The authors indentified a high rate of failure in this investigation. Over 50% of the dyslexic students failed two of the four tests, and each of the 77 failed at least one component. The most sensitive tests were binaural fusion and filtered speech with less variation from the norm in the remaining two components. The effect of maturation in central audition was measured in each of the four tests. The data suggest: 1. the scores are lower in the early ages in each test; 2. that rapidly alternating speech and competing sentences approach the normal range albeit somewhat delayed; and 3. that binaural fusion and filtered speech improve in score somewhat but rather moderately and never approach the normal range. Based upon the central auditory data and in conjunction with the anatomical pathways of vision, the authors suggest the site of lesion to be in the temporo-parietal cortex and the association fibers.

Adolescent↗