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Biomedical subjects

W I Smith

Publications and source records attributed to W I Smith.

At least 19 recordsLinked to original sources
PubMed1996

Acute gastrointestinal toxic effects of suspensions of unencapsulated and encapsulated ibuprofen in rats.

PURPOSE: The study examined the gastrointestinal (GIT) toxicity effects of suspensions of encapsulated and unencapsulated ibuprofen in male Wistar rats. METHODS: Rats were randomly divided into four experimental groups and four control groups, and dosed with suspensions of encapsulated and unencapsulated ibuprofen (17 mg/kg and 44 mg/kg). Bethanechol chloride, a cholinomimetic agent (5 mg/kg), was administered 30 minutes after the dosing, to induce gastric irritation. Blood plasma concentrations were monitored in another set of rats for 12 hours using the encapsulated and unencapsulated systems, to establish drug release and exposure to the mucosa. RESULTS: Evaluation of the upper GI segments after 7 hours revealed that the 44 mg/kg dose of the encapsulated drug significantly reduced the number of lesions present compared to the unencapsulated drug (p < 0.05). At 17 mg/kg, the encapsulated drug reduced toxicity, but not significantly compared to the unencapsulated ibuprofen. Necrosis of the mucosa was observed histopathologically in the unencapsulated drug at both doses, whereas the encapsulated drug treatment revealed preserved mucosa. The encapsulated system had a maximum plasma concentration, Cmax, and time taken to reach Cmax, (Tmax) of 26.7 mu g/ml +/- 1.5 and 3.6 +/- 0.2 hr, respectively. The area under the plasma concentration-time curve, (AUC(0-12)), was 158.8 +/- 23.5 mu g.h/ml, confirming drug release and absorption. CONCLUSIONS: Encapsulation of ibuprofen significantly reduced gastrointestinal toxicity especially at the higher dose level and drug was released enough to subject the GI mucosa to irritation, but without the usual toxic effects.

Animals↗
PubMed1996

Technetium-99m-MAG3 renal studies in spinal cord injury patients: normal range, reproducibility, and change as a function of duration and level of injury.

UNLABELLED: The normal range, reproducibility, and change as a function of duration and level of injury for Tc-99m-MAG3 renal studies were quantitated in spinal cord injury (SCI) patients. METHODS: Five SCI patients without evidence of renal disease in each of four groups: less than 2 months, 2-12 months, 1-2 years, and greater than 2 years from time of injury, were each studied twice. There were at least two patients with paraplegia and two with tetraplegia in each group. Renal clearance (camera based method), percent function in each kidney, time of peak renal parenchymal activity, and half time of parenchymal activity following the peak were evaluated. The peak and half times were determined with regions of interest (ROIs) over the entire kidney and over just the cortex. All results were compared to normal ranges previously established in normal subjects of the same age range using the same methodology. RESULTS: Renal clearance in the less than 2 month SCI patients was not significantly different from normal subjects in either paraplegic or in tetraplegic individuals. However, clearance in tetraplegics was increased by 28.5% at 2-12 month, increased by 50.6% at 1-2 years, and decreased by 25.9% at greater than 2 years compared to normal subjects (all P < 0.02). Clearance in those with paraplegia showed a similar, but less marked, trend (P = NS). The time of peak parenchymal activity when measured with cortical ROIs did not vary among patient groups or level of injury, but was increased compared to normal subjects (P < 0.05). The percent function in each kidney and half time following the peak were symmetrical, did not differ among patient groups or with level of injury, and did not differ from normal subjects. The parenchymal peak time was significantly shorter with cortical rather than renal ROIs in all patient groups (P < 0.05). In serial studies in the same patient the percent standard deviation in total renal clearance was less than between single studies in different patients, but the decrease was significant for only the right kidney (P < 0.03), and the decrease was not as great as in normal subjects. In addition, the percent standard deviation for percent function in each kidney was significantly less than the percent standard deviations in single studies (P < 0.02). There were no significant differences between intra- and interpatient studies for any other parameter. CONCLUSION: We conclude that: (1) renal clearance measured with Tc-99m-MAG3 in tetraplegic patients increases significantly during the first 2 years following injury and decreases significantly thereafter; there is a similar, but much less marked, trend in paraplegics, (2) parenchymal peak times with cortical ROIs occur later for SCI patients than for normal subjects, and (3) there is more intrapatient variation in total renal clearance and percent renal clearance on a side in SCI patients than in normal subjects suggesting that it may be harder to study SCI patients reproducibly. These findings should be taken into account when performing and interpreting Tc-99m-MAG3 renal studies in SCI patients.

Adult↗
PubMed1994

Technetium-99m-MAG3 renal studies: normal range and reproducibility of physiologic parameters as a function of age and sex.

UNLABELLED: The normal range and reproducibility of common physiologic parameters for 99mTc-MAG3 renal studies were quantitated in normal subjects. METHODS: Six females and six males in each of three age groups, 21-40, 41-60 and 61-80 yr, were each studied twice. Renal clearance (camera based method), percent function in each kidney, time of peak renal parenchymal activity and half time of parenchymal activity following the peak were evaluated. The peak and half times were determined with regions of interest (ROIs) over the entire kidney and over the cortex only. RESULTS: There were no significant differences between sexes for any parameter. The only significant difference among age groups was a decrease in renal clearance, normalized for body surface area, with increasing age (p < 0.01). The percent function in each kidney, time of peak parenchymal activity and half time following the peak were symmetrical and did not vary with age or sex. The peak times were always less with cortical ROIs (p < 0.05). In serial studies in the same subject the percent s.d. for clearance and percent function in each kidney was less than half of the percent s.d. in single studies, suggesting that at least one half of the error is due to intersubject variation (p < 0.05). CONCLUSIONS: We conclude that: (1) renal clearance decreases with age in normal subjects, (2) cortical ROIs are superior to renal ROIs in measuring peak parenchymal activity, and (3) variation in clearance and percent function per kidney in serial studies is approximately one half the variation in single studies.

Adult↗
PubMed1993

"Binge" versus steady drinking: effects on the liver in the ovariectomized rat.

Substantial interest exists as to whether or not differential effects in liver injury based on the pattern of alcohol intake exist; and further, if they do, are they simply a function of the total dose over time. A rat model in which ethanol (ETOH) at doses of 12%, 24%, or 36% of total calories was isocalorically administered for 4 months either daily or intermittently (4 days of ETOH, 3 days of control diet, repeatedly) was used to assess this question. There were significant differences in the two feeding pattern groups between 36% ETOH rats for the liver weight corrected for body weight, the fat infiltration score, the total amount of ETOH consumed/mg body weight, the proportion of animals with a fat infiltration score > 2, and albumin levels. There was a significant difference between 12% ETOH rats for the liver weight corrected for body weight. Of particular relevance is the comparison to be made between Daily 12% ETOH and Binge 24% ETOH animals, because these two groups consumed an identical total amount of ETOH/mg body weight (Daily: 445 +/- 5 vs. Binge: 468 +/- 15) and thus these animals are comparable in terms of ETOH dose over time but different in terms of the pattern of ETOH exposure. There were no differences in the liver/body ratio (Daily: 235 +/- 6 vs. Binge: 232 +/- 4), fat infiltration score (Daily: 2.5 +/- 4 vs. Binge: 2.4 +/- 0.3), the proportion of animals with a fat infiltration score > 2 (Daily: 5/10 vs. Binge: 4/8), or albumin levels (Daily: 3.0 +/- 0.1 vs. Binge: 3.1 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1983

Genetic linkage and HLA association in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Twenty-eight families of patients with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency were studied to evaluate the specific HLA linkage relationship and HLA antigen association to the 21-OH deficiency gene. Genotype assignment, based on hormonal studies (ACTH stimulation) and HLA genotyping, correlated very well (p less than 0.01) in 23 unaffected sibs of children with 21-OH deficiency further supporting the genetic linkage of the 21-OH deficiency gene to the HLA complex. One family was informative for the placement of the 21-OH deficiency gene outside the HLA complex on the HLA-DR locus side. In this family HLA-A, B, C, DR, MT, MB, and glyoxylase typing and mixed lymphocyte culture was performed. An association of 21-OH deficiency and the HLA-A3 antigen was noted in the 28 families. This association is not secondary to the association of the 21-OH deficiency gene with HLA-BW47.

Adrenal Hyperplasia, Congenital↗
PubMed1982

Familial occurrence of renal and intestinal disease associated with tissue autoantibodies.

Chronic tubulointerstitial renal disease and villous atrophy of the small intestine occurred in two first cousins. Both had protracted diarrhea with malabsorption and died despite intensive parenteral alimentation. In one patient signs of generalized proximal tubular dysfunction developed, followed by nephrotic syndrome and progressive renal insufficiency. A renal biopsy specimen disclosed severe tubulointerstitial disease and membranous glomerulopathy. In this patient, circulating immune complexes were detected and granular deposits of IgG and C3 were seen in the intestinal epithelial cells by direct immunofluorescence. Antiintestinal antibodies (IgG class) were demonstrated by indirect immunofluorescence. The other patient had interstitial nephritis but no glomerular abnormality. On direct immunofluorescence, both patients had confluent granular staining of the renal tubular basement membranes. These immunopathologic studies suggest a common immunologic mechanism in the pathogenesis of the renal and gastrointestinal disorders in these infants.

Autoantibodies↗
PubMed1982

Secretory component and serum immunoglobulin A deficiencies with intestinal autoantibody formation and autoimmune disease: a family study.

A teenage boy with both secretory component deficiency and selective serum immunoglobulin A deficiency also developed pernicious anemia, insulin-dependent diabetes mellitus, pancreatic insufficiency, lymphopenia, intestinal candidiasis, and anti-intestinal antibody. The patient's father had pernicious anemia and diabetes mellitus while the paternal grandfather also had pernicious anemia. Because the patient had inherited the paternal grandmother's human leukocyte antigen complex, there was no direct association between pernicious anemia and the genetic markers. The presence of multiple immunologic abnormalities in a single patient supports the concept of an underlying defect in immune regulation as a central factor in the pathogenesis of these disorders.

Adolescent↗
PubMed1982

The value of ultrasound for monitoring ovarian responses to gonadotropin stimulant therapy.

Ultrasonic measurement of ovarian follicles was used in conjunction with conventional measurement of urinary oestrogen output to monitor responses in infertile women receiving gonadotrophin stimulant therapy. In the 21 women who conceived during the first 15 months, in which this combined monitoring was used, ultrasound proved superior to oestrogen measurement alone for assessing follicular maturity and hence deciding when to administer the ovulating dose fo chorionic gonadotrophin. The use of ultrasound imaging improves efficiency of treatment with gonadotrophin stimulant therapy, but is not predictive of multiple pregnancy or of hyperstimulation.

Adult↗
PubMed1980

Altered immunity in male patients with alcoholic liver disease: evidence for defective immune regulation.

We sought evidence for altered immunity in patients with alcoholic liver disease, and we correlated the observed immunologic abnormalities with the extent of histologically proven liver disease. Total circulating lymphocytes and the absolute number of T lymphocytes were decreased in alcoholics (p less than 0.01) compared to controls. Immunoglobulins G and A were elevated significantly (p less than 0.05) in alcoholic patients with hepatic fibrosis or cirrhosis compared to controls and alcoholics without liver histopathology. In alcoholics with fibrosis or cirrhosis at time of admission, IgE levels were also elevated (p less than 0.01) but decreased 50% during hospitalization. Forty-eight percent of the patients with alcoholic liver disease had antibodies to small bowel epithelium, and 33% had antibodies to fibroblast cytoplasm. In addition, we found that alcoholics immunized with polyvalent pneumococcal polysaccharide responded with significantly elevated (p less than 0.025) antibody titers compared to hospitalized controls. In aggregate, these findings in patients with alcoholic liver disease are consistent with a defect in immune regulation.

Bacterial Vaccines↗
PubMed1979

Hypothalamic-pituitary-gonadal dysfunction in men using cimetidine.

We studied the effect of cimetidine therapy (1200 mg per day by mouth for nine weeks) on the hypothalamic-pituitary-gonadal axis of seven men. There was a 43 per cent mean reduction in sperm count after therapy. The luteinizing hormone response to luteinizing hormone releasing factor was also reduced, and a statistically significnat rise in plasma testosterone occurred, although it was less than that before therapy. Gonadotropin responses to provocative clomiphene stimulation were inadequate when compared with those of controls. Cimetidine did not affect the responses of thyroid-stimulating hormone, prolactin, growth hormone and thyroxine to thyrotropin releasing factor. Caution is advisable in administration of cimetidine for prolonged periods to young men.

Adult↗
PubMed1978

Immunopathology of juvenile-onset diabetes mellitus. I. IgA deficiency and juvenile diabetes.

There is an increased prevalence (P less than 0.001) of IgA deficiency in children with juvenile-onset insulin-dependent diabetes mellitus (9/366) but not in adults with insulin-dependent diabetes (0/421). The juvenile diabetics with IgA deficiency have other immune-associated diseases, such as thyroiditis and chronic active hepatitis, and have a history of infections. Four of the nine IgA-deficient diabetics we studied have autoantibodies to endocrine organs. Seven of eight have the HLA-B8, a proportion significantly (P less than 0.05) greater than control populations. Based on the clinical findings of IgA deficiency and multiple autoantibodies in patients with ataxia-telangiectasia and chronic mucocutaneous candidiasis, diseases associated with thymus deficiency, we suspect that thymus deficiency and autoimmunity may play a role in the pathogenesis of some types of juvenile-onset diabetes mellitus. In addition, an excess morbidity of the IgA-deficient juvenile diabetic population may explain the lack of IgA deficiency in older insulin-dependent diabetic individuals.

Adolescent↗