Biomedical subjects

J J Welsh

Publications and source records attributed to J J Welsh.

At least 19 recordsLinked to original sources

PubMed1995

Developmental toxicity of sodium fluoride in rats.

Despite the chronic exposure of the US population to fluoridated drinking water since the 1940s, existing studies have been judged inadequate to determine any potential reproductive or developmental hazard. This study was conducted to determine the effects of sodium fluoride (NaF) on foetal development. Sperm-positive female rats were given 0, 10, 25, 100, 175 or 250 ppm NaF daily throughout gestation. They were dosed by drinking water to mimic human exposure to fluoridated water. No dose-related behavioural changes or maternal clinical signs were noted. Fluid consumption by females in the 175- and 250-ppm groups was significantly less than that of the control females. Because of this decreased fluid consumption, the daily amount of NaF ingested (0, 1.4, 3.9, 15.6, 24.7 and 25.1 mg/kg body weight) was less than expected at the two high levels. Feed consumption decreased significantly at 250 ppm, and body weights of pregnant females reflected feed consumption trends. The mean number of viable foetuses per female in all treated groups was similar to that of the control group. The significant decrease in the mean number of implants per litter in the 250-ppm group is probably linked to the lower mean number of corpora lutea in this group. The occurrence of in utero deaths was similar in the control and treated groups. Foetal growth (in terms of foetal body weight and crown-rump length) was not affected by NaF, despite the fact that the dams in the 250-ppm group ate significantly less feed and drank significantly less fluid. There was no dose-related increase in the number of external anomalies in foetuses due to NaF ingestion. At the doses given, NaF had no effect on the development of specific bones, including sternebrae. A significant increase was seen in the average number of foetuses with three or more skeletal variations in the 250-ppm group; the number of litters with foetuses with three or more skeletal variations was increased in the 250-ppm group also, but the increase was not significant. There was no dose-related effect of NaF on the incidence of soft tissue variations.

Abnormalities, Drug-Induced↗

PubMed1994

Developmental effects of combined exposure to ethanol and vitamin A.

The potential for ethanol (EtOH) to influence the developmental toxicity of vitamin A was investigated. 11 groups of approximately 31 FDA-bred Osborne-Mendel rats received either a control or isocaloric 6.4% EtOH liquid diet (containing 4000 IU vitamin A/litre) ad lib. The vehicle control, EtOH and pair-fed (pair-fed against the EtOH group) groups received corn oil (the vehicle) by gavage. Vitamin A was administered by gavage without EtOH at 40,000, 80,000, 120,000 or 160,000 IU/kg daily. Vitamin A was administered by gavage at 10,000, 20,000, 40,000 or 80,000 IU/kg with EtOH ad lib., daily throughout the study. Combined EtOH and vitamin A resulted in significant reductions in maternal diet consumption and body weight when doses of vitamin A were as low as 10,000 IU/kg. The most severe effects on overall (days 0-20) maternal body weight gain were observed in the groups receiving 120,000 or 160,000 IU vitamin A/kg alone or EtOH in combination with 80,000 IU vitamin A/kg. The overall diet consumption (days 0-20) paralleled the overall weight gain. In general, pups exposed to ethanol and vitamin A had a tendency to weigh less than those exposed to vitamin A alone, but to weigh more than those exposed to EtOH alone. EtOH combined with vitamin A at 80,000 IU/kg resulted in an increased incidence of cleft palate relative to the vehicle control or either treatment alone. The incidence of exencephaly and protruding tongue was significantly greater in the group given vitamin A at 160,000 IU/kg, compared with the vehicle control group. The most consistent statistically significant skeletal finding in the groups receiving combined treatment was a treatment-related increased incidence of supernumerary ribs [14th rib (C7), 14th rib bud (L1) and 15 ribs]. In addition, the incidence of misshapen zygomatic arch was also significantly increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg. The incidence of moderately enlarged renal pelvis and severely enlarged ureter proximal to the kidney was increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg relative to the vehicle control, or either treatment alone. Therefore, for some of the endpoints examined in this investigation, it would appear that ethanol potentiates the developmental effects of vitamin A.

Abnormalities, Drug-Induced↗

PubMed1994

Effect of ethanol and vitamin A excess on vitamin A status in the liver, plasma and foetuses of pregnant rats.

The effect of maternal consumption of dietary ethanol and high doses of vitamin A by gavage was investigated by evaluating plasma, liver and foetal vitamin A in Osborne-Mendel pregnant rats with a view to assessing whether ethanol modulated the potential toxicity of excess vitamin A. All groups received 4000 IU vitamin A/litre in a liquid diet. Ethanol-exposed groups also received 6.4% (v/v) ethanol in the liquid diet. Vitamin A was administered by gavage once per day in corn oil in doses ranging from 10,000 to 160,000 IU/kg body weight. Plasma vitamin A levels in ethanol-exposed groups were similar to levels in a pair-fed group. Plasma vitamin A levels were similar in the group given ethanol plus 40,000 IU vitamin A/kg and the group given 40,000 IU vitamin A/kg only, but were higher in the group receiving ethanol plus 80,000 IU vitamin A/kg than in the group given 80,000 IU vitamin A/kg only. Retinyl esters were present in the plasma of animals receiving 160,000 IU vitamin A/kg only, indicating possible saturation of the liver with vitamin A. Retinyl palmitate levels in female foetuses of the group administered ethanol plus 80,000 IU vitamin A/kg were significantly higher than those of the group administered 80,000 IU vitamin A/kg only; no significant differences in levels of retinyl palmitate in male foetuses were observed between these two groups. This observation suggests a possible sex difference in the modulation of vitamin A toxicity by ethanol in the foetus.

Administration, Oral↗

PubMed1993

Foetal development in rats fed AIN-76A diets supplemented with excess calcium.

This study was designed to evaluate the developmental effects of moderate dietary calcium increases in rats fed nutritionally adequate diets. Female Charles River CD/VAF Plus rats were given 0.50 (control), 0.75, 1.00 or 1.25% dietary calcium as calcium carbonate in AIN-76A diets for 6 wk before mating, during mating and for 20 days of gestation. On gestation day 20, the animals were killed and caesarean sections were performed. Both the non-pregnant and pregnant rats in the 0.75, 1.00 and 1.25% groups ate slightly more than did the control group during most of the intervals measured, but not all the increases were statistically significant. There was no consistent pattern of increase or decrease in weight gain. No dose-related changes were found in maternal clinical findings, the average number of implantations, resorptions and viable foetuses, or foetal length or weight. Under the conditions of the study, there were no statistically significant increases as compared with the control group in the litter incidence regarding specific external, visceral or skeletal variations of the foetuses. Dietary calcium was neither foetotoxic nor teratogenic at the concentrations used.

Analysis of Variance↗

PubMed1992

Radiographic analysis of deep cervical abscesses.

Correlation of the radiographic examination and the clinical evaluation of deep cervical abscesses contributes to the surgical program for exposure and drainage. The deep cervical spaces are analyzed with reference to local anatomy, sources of infection, potential for lateral and vertical extension, and identification of regional expansion by standard and computed tomography. Guidelines and recommendations are proposed for clinical application and supported by illustrative cases.

Abscess↗

PubMed1991

Massive orofacial abscesses of dental origin.

Massive cervicofacial abscesses of dental origin are relatively rare, and may be associated with serious and grave morbidity. In extreme cases, an occasional fatality may result from regional complications. Three cases are presented that describe the clinical and radiographic evaluation and the surgical approaches for abscess drainage. Specific attention is directed toward 1) the management of imminent airway obstruction, 2) the application of computed tomographic technology for localization and surgical planning, and 3) current antibiotic therapy.

Abscess↗

PubMed1990

Developmental effects and mineral interactions in rats fed textured vegetable protein.

The teratogenic effects of feeding a diet based on textured vegetable protein to Long-Evans rats were studied along with maternal and fetal mineral interactions and their relationship to diet composition. Pregnant rats were fed purified diets containing 18% protein as casein (CAS), textured vegetable protein (TVP, from defatted soy flour) with 18 mg Zn/kg, or TVP diet with 100 mg Zn/kg. A fourth group was fed diet NIH-31. The animals received their diets throughout pregnancy and were sacrificed on day 20 of gestation. Fetuses were examined for developmental effects, and mineral levels were determined in maternal and fetal tissues by inductively coupled argon plasma-atomic emission spectrometry. Females fed the casein diet or diet NIH-31 had normal weight gains throughout pregnancy and their progeny exhibited normal development. The animals on the TVP-containing diet with 18 mg Zn/kg had decreased food consumption and body weights, and their fetuses exhibited developmental anomalies as well as reductions in size and weight. These developmental alterations may be the result of decreased zinc levels in the fetal tissues, caused by reduced bioavailability of the trace element in the maternal diet. Significant increases in tissue iron accompanied the low zinc levels. No developmental effects were found in animals receiving the high Zn-TVP diet, and mineral data from these animals were not significantly different from the casein group.

Animals↗

PubMed1990

Role of angiography in the management of refractory epistaxis.

When interruption of the related arteries fails to control epistaxis, angiography is recommended for identification of the vascular base, the collateral circulation, and the possibility of arterial abnormalities. Criteria are proposed for utilization of vascular mapping, and relevant cases are cited to support the specific indications for application.

Aged↗

PubMed1989

Study of the teratogenic potential of FD & C Red No. 40 when given by gavage to rats.

Osborne-Mendel rats were intubated with FD & C Red No. 40 at dose levels of 0, 30, 75, 150, 300, 600, or 1000 mg/kg body weight/day on days 0-19 of gestation. No developmental toxicity was observed when the animals were killed on day 20 of gestation. No dose-related changes were seen in maternal daily observations, food consumption, body-weight gain or implantations, or in foetal viability, body weight, body length, sex distribution or external variations. Skeletal and soft-tissue development appeared similar in foetuses of all groups. The isolated increases that occurred in the number of male foetuses, number of females with two or more resorptions, number of litters with three or more sternebral variations and incidence of 14th rib bud are considered random occurrences and were not related to dosage.

Administration, Oral↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1987

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↗