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%.

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.

Endoscopic examination of corrosive injuries of the upper gastrointestinal tract.

The authors present the case histories of five patients who have sustained corrosive injuries of the upper gastrointestinal tract. Flexible endoscopic examination was successfully carried out in each patient to assess the extent of the injury and anticipate further therapeutic needs. Three patients sustained major gastric lesions, i.e., strictures or bleeding following the ingestion of alkali, acids, or phenol, and one instance of esophageal stricture was recognized. The endoscopic observation of antral gangrene was inexorably followed by antral stricture requiring surgical management. One fatality followed rigid esophagoscopic examination which resulted in esophageal perforation.

Problems of diagnosis in the evaluation of mediastinal sarcoidosis.

The diagnosis of sarcoidosis can be established when the case meets the criteria of clinical course, radiologic findings, and supportive histology. When there is variation from the established criteria and the clinical course of age, systemic evidence of disease or the radiologic findings of unilateral or solitary adenopathy are encountered, then ongoing evaluation is necessary to identify a possible second disease existence. Cases have been presented which indicate some problem requiring further investigative studies before acceptance of the diagnosis of sarcoidosis.

Fractures of the edentulous maxilla and mandible.

An evaluation and treatment of fracture of the edentulous maxilla and/or mandible is presented. The Le-Fort classification of maxillary fractures is the foundation for the program of care. Immobilization techniques are based upon the support of a fracture by suspension from the adjacent stable segments to the modified prosthesis. The mandibular fractures are repaired by interosseous wire fixation in the body and symphysis region, the other fracture sites are supported by circumferential wiring to the prosthesis for immobilization. General principles of time of repair, diet, types of healing factors are reviewed.

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.

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.

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.

Syndromal vertigo identified by magnetic resonance imaging and angiography.

The advent of magnetic resonance imaging and angiography has clarified the location and vascular basis for vertigo of a syndromal type. The composite presentation of a vestibular symptom with evidence of cranial nerve or cerebellar dysfunction suggests a lesion within the pons, medulla, or cerebellum. The location may be exactly defined by noninvasive techniques and appropriate therapy can be initiated. Clinical examples are presented; the syndromes of vertebrobasilar artery perfusion disorder are described, and appropriate images are illustrated for confirmation.

Evaluation of the vestibular system by magnetic resonance angiography.

This report describes the normal arterial patterns of the vestibulocerebellar regions visualized by magnetic resonance angiography. Variations in the vertebrobasilar arterial system are described, limitations in imaging are discussed, and collateral connections within the cerebellar vessels and the circle of Willis are reviewed. Clinical correlations are defined between the vestibular nuclei, the associated intraaxial tracts, and with specific posterior cerebral and brain stem arteries.

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.

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)

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.

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.

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.

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.

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.

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.

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.

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.