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Biomedical subjects

J J Welsh

Publications and source records attributed to J J Welsh.

At least 19 recordsLinked to original sources

Vertigo: analysis by magnetic resonance imaging and angiography.

The relationship of vascular disease of the vertebrobasilar artery system to isolated vertigo was examined by magnetic resonance imaging and angiography. Eighty-nine individuals complaining of vertigo were evaluated by standard otoneurologic investigations, and the data were correlated with the vascular patterns of the cervical region and posterior fossa. The age distribution extended from the fourth decade to the ninth decade; the peak occurrence was observed in the eighth. Approximately 85% of the group experienced numerous episodes of vestibular dysfunction from months to years before examination; the remaining segment was examined following the first episode due to severity or persistence of symptoms. The criteria for vascular abnormality proposed by the authors are based upon comparison with previous normal findings. Approximately 52% of the cohort demonstrated abnormal configurations or evidence of diminished flow within the vertebrobasilar artery system. Of this segment, a vertebral artery was most frequently abnormal, in 76%; the basilar artery was judged pathological in 32%, and combined disease of several arteries was evident in 20%.

Adult↗

Basilar artery and vertigo.

Our goal was to identify by magnetic resonance angiography the specific vascular abnormalities of the basilar artery that can be related to hypoperfusion disorders and produce symptoms of vertebrobasilar insufficiency. A classification of regional vascular perfusion disorders based on developmental malformations and intrinsic and extrinsic angiopathies was formulated from an analysis of individuals with these disorders. Specific angiographic abnormalities such as tortuosity, stenosis, thrombosis, and dolichoectasia were identified in subjects with vestibulocerebellar dysfunction. Charts and radiographic images were examined with respect to the history, physical evidence, and vascular configuration, and the data were integrated for comprehensive analysis. We found that abnormalities identified by magnetic resonance angiography could be correlated with symptoms due to vascular insufficiency. Cases are presented that document the developmental and acquired arterial disorders that may be considered the etiologic factors for regional perfusion deficits.

Adolescent↗

Function of a hearing aid under stressful conditions.

The auditory function of individuals with normal hearing was compared with that of hearing-aided subjects of similar age to determine whether amplification remediates hearing impairment under stressful auditory situations. The specific tests of listening in a competitive noise environment and identifying moderately compressed speech were introduced to adequately aided individuals. The data indicate that noise had an impact on auditory function to a much greater degree in aided individuals than in matched counterparts with normal hearing. The data derived from acceleration of simple sentences delivered to the aided group suggested that contrary to basic tonal sensitivity, the capacity to understand the stimulus was greatly compromised. The authors discuss cochlear damage and central auditory impairment as they relate to the limitations of amplification for sensorineural hearing loss.

Adult↗

Food and Drug Administration proposed testing guidelines for reproduction studies. Revision Committee. FDA Guidelines for Developmental Toxicity and Reproduction, Food and Drug Administration.

In the United States, the Food and Drug Administration (FDA) is the agency responsible for ensuring that the direct food additives and color additives used in food are safe for all consumers. In order to determine the safety of these additives for consumption, appropriate information and results from a series of tests must be made available to the agency. In 1982, in an effort to provide guidance to the food industry concerning the appropriate tests for the determination of safety, the FDA issued the Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Foods, commonly referred to as the Redbook. In 1993, based on the expansion of technology and the use of food additives, as well as the refinement of the scientific criteria for establishing safety, the FDA updated its guidelines and issued the draft Redbook II. Since Redbook II was issued, additional refinements have been made in the procedures for the multigeneration reproduction study and for the assessment of effects on male reproduction. The latest proposed guidelines for multigeneration studies are provided here.

Animals↗

Food and Drug Administration proposed testing guidelines for developmental toxicity studies. Revision Committee. FDA Guidelines for Developmental Toxicity and Reproduction, Food and Drug Administration.

The Food and Drug Administration (FDA) is the agency responsible for ensuring that the direct food additives and color additives used in food in the United States are safe for all consumers. In 1982, in an effort to provide guidance concerning appropriate tests, the FDA issued Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food, commonly known as the Redbook. The Redbook included detailed guidelines for testing the effects of direct and indirect food and color additives on mothers and their developing fetuses. Based on refinements in safety assessment and risk evaluation as well as expansion of knowledge concerning the metabolism and pharmacokinetics of food and color additives, the need to revise and update the 1982 document became apparent. In 1993, Redbook II in draft form was made available for public comment. Since then, test end points and developmental landmarks have been refined. The latest proposed guidelines for developmental toxicity studies are provided here.

Animals↗

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.

Basilar Artery↗

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.

Adult↗

Learning disabilities and central auditory dysfunction.

Hearing loss, whether peripheral or central, compounds the communication and educational problems of the learning disabled student. A central auditory processing disorder uniquely interferes with both the input and integration of verbal information, further resulting in a potentially permanent cognitive dysfunction during the developmental period of acquisition of language. Illustrative cases are presented that indicate the panorama of cognitive dysfunction associated with the learning disabled status. Methods of evaluation and identification and diagnostic criteria are correlated with auditory, visual, and academic performance. Comments regarding clinical awareness, prompt recognition, and ensuing individualized remediation are submitted.

Adult↗

Early sound deprivation and long-term hearing.

The long-term effects of hearing loss in early life were analyzed by tests of central auditory function. A majority of individuals failed the Compressed Speech identification with statistically significant results. There was an impact on a minority of individuals evaluated by Dichotic Sentences; little impairment was noted through Speech Reception in Noise. Delayed maturation of the central auditory complex may improve these findings, although during the period of investigation a negative impact was measured. Other issues of diagnosis, remediation, and the consequences of short- and long-term deafness are discussed.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗