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Biomedical subjects

S R Harris

Publications and source records attributed to S R Harris.

At least 19 recordsLinked to original sources

Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports.

Although autistic-like behaviors were described even in the earliest reports of fetal alcohol syndrome, it was only recently that fetal alcohol syndrome and autism were reported as a dual diagnosis in six school-aged children. The purpose of the present series of case reports is to describe marked autistic characteristics in three much younger children (25-36 months) with histories of prenatal exposure to alcohol and other drugs. The behavioral characteristics of these children are described and compared with current diagnostic criteria for autistic disorder. In addition, longitudinal scores on the Bayley Scales of Infant Development are provided to underscore the marked developmental delays shown by each of the children. Limitations of these case reports are discussed with suggestions for future prospective research.

Autistic Disorder

Chronic energy restriction versus energy cycling and mammary tumor promotion.

Chronic energy restriction significantly inhibits mammary tumor promotion in rodents. The present work studied the effect of short-term, intermittent energy restriction or energy cycling on mammary tumor promotion since this feeding paradigm mimics the dieting habits of humans. Female Sprague-Dawley rats were given 7,12-dimethylbenz[a]anthracene (DMBA) at 50 days of age (5 mg ig). One week later, rats were randomly divided into three dietary groups. One group was fed ad libitum throughout the study (AL), another (ER) was fed 40% fewer calories than the AL group, and a third, energy-cycled group (EC) was fed in repeated cycles of 2 days of feeding at a level comparable to that of AL rats followed by 2 days of 40% energy restriction. At 10 weeks post-DMBA, the mammary tumor incidences in the AL and EC groups were the same, but incidence in the ER group was significantly lower. A second experiment examined serum levels of three hormones thought to play a role in mammary tumorigenesis. After 12 or 24 days on diet, ER rats had lower insulin levels compared with the other groups. Serum insulin levels in AL and EC rats were the same. After 24 days on diet, estradiol levels were significantly lower and corticosterone levels higher in the ER and EC groups compared with the AL group. Although energy cycling is a type of energy restriction that lowers overall weight gain and energy intake, it does not inhibit mammary tumor promotion as does chronic energy restriction. These data also suggest that feed efficiency and serum insulin levels correlate with susceptibility to mammary tumor promotion.

9,10-Dimethyl-1,2-benzanthracene

Failure of high fat diets to promote mammary cancers in spontaneously hypertensive rats.

Rat strains differ in their susceptibilities to chemically-induced mammary carcinogenesis. The present study tested the hypothesis that the spontaneously hypertensive rat (SHR) strain is resistant to mammary carcinogenesis. Resistance would imply the presence of the mammary carcinoma suppressor (MCS) gene. Therefore, we also wanted to test the ability of this gene to inhibit mammary tumor promotion in the presence of high fat diets. Female SHRs were treated with DMBA (5 mg/rat) at 50 days of age and transferred to either a 20% corn oil or 19% menhaden oil + 1% corn oil diet one week later. At 17 weeks post-DMBA none of the rats in either group developed mammary carcinomas. Multiple palpable nodules formed in the mammary gland indicating that initiation had occurred. We conclude that the SHR strain is genetically resistant to DMBA-induced mammary carcinogenesis by mechanisms involving a blockade of promotion.

9,10-Dimethyl-1,2-benzanthracene

Oxygen free radicals and antioxidants: a review.

In 1989, nearly 43% of deaths in the United States were due to some form of cardiovascular disease, and 23% were caused by cancer. Thus, two of every three people in this country die from either cardiovascular disease or cancer. Based on both experimental and epidemiological evidence, investigators believe that free radicals play a critical role in the development of both diseases. Low levels of antioxidants, which increases free radical activity, are clearly associated with an increased risk of these diseases. This link has led to the conclusion that use of antioxidant vitamin supplements to scavenge free radicals could potentially decrease the risks of cancer and cardiovascular disease. Results from numerous studies to date have been very promising, although a true protective or preventive causal relationship has not yet been established. Numerous primary and secondary intervention trials currently underway should more definitively assess the role of antioxidants in disease prevention. In the interim, many people feel the evidence is now strong enough to begin supplementation on their own. The pharmacist is in a position to advise patients on the safe and moderate use of antioxidants. The antioxidants discussed in this article are relatively non-toxic, with the exception of vitamin A. The possible benefits of vitamin A are better achieved with the use of beta-carotene. Megadose antioxidant supplementation does not appear to provide any additional benefit beyond what a more moderate supplement can provide and should therefore be discouraged. Taking a trace mineral with antioxidant potential is generally a waste of money, provided the patient is not initially deficient in the element.(ABSTRACT TRUNCATED AT 250 WORDS)

Antioxidants

High fish oil diet increases oxidative stress potential in mammary gland of spontaneously hypertensive rats.

1. The purpose of this study was to determine whether high omega-3 (19% menhaden oil, 1% corn oil) or high omega-6 (20% corn oil) fatty acid diets would decrease expression of hypertension in the female spontaneously hypertensive rat (SHR), promote tumourigenesis in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model of mammary cancer or increase the susceptibility of the mammary gland to lipid peroxidation. A group of rats on a 5% corn oil diet served as the low fat control group. 2. We found that the high omega-3 and high omega-6 fatty acid diets did not significantly decrease mean arterial pressure. Marked differences occurred between the effects of omega-3 and omega-6 high fatty acid diets on baseline oxidation, auto-oxidation and iron-ascorbate catalyzed oxidation. The omega-3 diet showed 675% increase in basal oxidation, a 2624% increase in auto-oxidation and a 4244% increase in iron-ascorbate catalyzed oxidation compared to the omega-6 diet in mammary tissue homogenates. Although all rats were given 5 mg DMBA (i.g.), no mammary tumours were observed in any of the dietary groups. 3. We conclude that: (i) high polyunsaturated fatty acid diets do not decrease blood pressure in the female SHR; (ii) high fish oil diet markedly increases oxidative potential in the mammary gland; and (iii) the female SHR is resistant to DMBA-induced tumourigenesis.

9,10-Dimethyl-1,2-benzanthracene

Low dose intranasal nafarelin for the treatment of endometriosis.

Twenty-five women with regular menstruation and laparoscopically confirmed endometriosis received 100 mcg nafarelin intranasally twice daily for six months in an open study. American Fertility Society (AFS) laparoscopic scores pre- and post-treatment, symptom severity, hormonal status, bone density and biochemical indices of bone turnover were studied. Five patients were still menstruating at three months and nafarelin was increased to 400 mcg daily. At the end of treatment, the median serum estradiol was 57 pmol/l and all patients were amenorrhoeic. AFS scores for endometriosis improved significantly in 19/23 (82.6%) patients (p = 0.001). Adhesions were not affected. Symptom severity scores were markedly decreased (p < 0.0001) and remained so six months after the end of treatment. Biochemical indices of bone activation were increased but bone loss was insignificant. During treatment, 23/25 patients reported hot flushes. Nafarelin 200 mcg daily significantly reduced signs and symptoms of endometriosis, although five patients needed a dosage increase before menses stopped. The study suggests that lower doses of nafarelin may be efficacious, although symptomatic changes should be treated with caution due to the open and non-comparative nature of the study.

Abdominal Pain

Parents' and caregivers' perceptions of their children's development.

Parents' or caregivers' perceptions of their infants' overall development may serve as a reliable screen for clinical decisions regarding the need for further assessment. To determine whether caregivers were accurate in estimating infant development, 27 caregivers were asked to answer four questions about their infants before standardized assessment by a paediatric physical therapist. Their responses were compared with the professional's ratings on the Bayley Scales of Infant Development. Specificity of the parents' estimate with the Bayley Mental Scale was 85.9 per cent and sensitivity 60 per cent; using the Bayley Motor Scale as the outcome criterion, specificity reached 90.9 per cent and sensitivity 80 per cent. Results of this pilot study support the accuracy of caregiver estimates of their infants' overall development, thus suggesting that professionals should pay close attention to caregivers' concerns about their children's development.

Caregivers

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats.

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit.

9,10-Dimethyl-1,2-benzanthracene

Fetal alcohol syndrome: review of the literature with implications for physical therapists.

The purpose of this review is to familiarize physical therapists with the diagnostic, clinical, and behavioral characteristics associated with fetal alcohol syndrome (FAS) and other alcohol-related birth defects. Through review of FAS research studies of both humans and animals, the prevalence, pharmacokinetics, and clinical features of this syndrome are described. Deficits in the areas of cognitive, behavioral, and motor development are also described. Particular attention is given to neuromotor differences and orthopedic abnormalities associated with FAS that may require consultation or intervention from physical therapists.

Abnormalities, Drug-Induced

Effects of prenatal alcohol exposure on neuromotor and cognitive development during early childhood: a series of case reports.

The purpose of this article is to present a series of case reports of infants and young children who were exposed to alcohol prenatally. The five infants and two 5-year-old twins in this series all presented facial features characteristic of prenatal alcohol exposure, and all had medical histories of maternal alcohol abuse. The neuromotor and cognitive development of these seven children is described by presenting results of standardized tests administered longitudinally. In addition, clinical observations of growth, behavior, feeding, and musculoskeletal development are provided. Following a discussion of these assessment results, implications for physical therapy intervention and the need for clinical research are provided. Because children with fetal alcohol syndrome or alcohol-related birth defects present a spectrum of developmental differences that often include areas of concern to physical therapists, we need to increase our involvement in the assessment and treatment of these children as well as in research efforts to examine the efficacy of these interventions.

Child, Preschool

Antagonism of acetaminophen hepatotoxicity by phospholipase A2 inhibitors.

A 250 mg/kg subcutaneous injection of acetaminophen (APAP) given to fasted mice was hepatotoxic as indicated by elevated serum alanine aminotransferase activity and electron microscopic studies. When extramitochondrial Ca2+ levels were 200 nM or greater, the APAP caused loss of mitochondrial Ca2+ homeostasis in a two step process that represents a sequence of events. The first step occurs 0 to 3 hours after APAP administration and the second step occurs 6 to 12 hours after APAP administration. Loss of mitochondrial Ca2+ homeostasis 6 to 12 hours after APAP correlates chronologically with nuclear damage as indicated by loss of nuclear Ca2+ sequestration between 6 and 12 hours after APAP administration. Pretreatment of mice with the phospholipase A2 (PLA2) inhibitors chlorpromazine or diltiazem one hour prior to APAP administration inhibits loss of mitochondrial Ca2+ homeostasis, prevents nuclear damage, and inhibits APAP hepatotoxicity as indicated by serum alanine aminotransferase activity and electron microscopic studies. This protective effect of chlorpromazine and diltiazem does not interfer with initial actions of APAP that influence mitochondrial function, but interfers with the sequence of events initiated by APAP that leads to loss of mitochondrial Ca2+ homeostasis and hepatotoxicity.

Acetaminophen

Instability of the intelligence quotient-motor quotient relationship.

The authors evaluated the stability over one- and two-year periods of the relationship between a cognitive measure (McCarthy General Cognitive Index) and a motor measure (McCarthy Motor Scale) to examine whether the cognitive-motor relationship changed significantly over time and whether children remained in the same service eligibility category, based on the cognitive referencing model. Results indicated substantial changes in the cognitive-motor relationship. Over a two-year period, more than 42 per cent of children changed their cognitive-motor relationship by at least 16 points. Children's eligibility for service, based on the cognitive referencing model, also fluctuated substantially over time. The authors conclude that the cognitive referencing model of triage is not an effective means of determining who should receive physical and occupational therapy services. Alternative methods are suggested.

Child

Metabolism of calcium antagonist Ro 40-5967: a case history of the use of diode-array u.v. spectroscopy and thermospray-mass spectrometry in the elucidation of a complex metabolic pathway.

1. The calcium antagonist, Ro 40-5967, is metabolized to a multitude of products by the rat and drug-related material is excreted predominantly via the bile. 2. Diode-array u.v. spectroscopy, following reverse phase h.p.l.c. separation of the partially purified metabolites, has been used to classify these compounds into six spectral classes which have been correlated with different metabolic reactions. 3. Connection of a mass spectrometer directly to the h.p.l.c. equipment by a thermospray interface, produced useful mass spectra. These, together with the u.v. spectra, enabled the structures of many metabolites to be elucidated. 4. Confirmation of structural assignments was provided by n.m.r. spectra of the major metabolites. 5. Major metabolic pathways included N-demethylation (16% of the biliary metabolites), hydrolysis of the ester side-chain (32%), hydroxylation at 4- (19%) and 5- (29%) positions of the benzimidazole ring, aromatization of the tetrahydronaphthyl system (26%), loss of the benzimidazole (15%) and glucuronidation of hydroxyl groups (81%).

Animals

Joint mobilization for children with central nervous system disorders: indications and precautions.

Because clinicians are introducing joint mobilization into treatment programs for children with cerebral palsy, we felt that a review of the procedure and its scientific basis would be timely. The goals of the introductory section of this article are to define joint mobilization as it has been used for adults with musculoskeletal disabilities, to discuss various rationales for its effects, to describe contraindications and precautions for its use, and to discuss its efficacy as reported in the research literature. The latter part of the article deals with the use of joint mobilization for children with central nervous system (CNS) disorders. In an effort to understand precautions for the use of joint mobilization in children, musculoskeletal development will be described both for typically developing children and for children with spastic cerebral palsy. Indications for using joint mobilization techniques in children with spasticity will be outlined. Specific neurodevelopmental disabilities for which joint mobilization would be strongly contraindicated will be listed. Finally, future research directions in evaluating reliability of assessment of joint dysfunction and efficacy of joint mobilization in children will be discussed.

Biomechanical Phenomena

Development of a clinical measure of postural control for assessment of adaptive seating in children with neuromotor disabilities.

The primary purposes of this article are to review the literature on seating assessment and to describe the development of a clinical evaluation scale, the Seated Postural Control Measure (SPCM), for use with children requiring adaptive seating systems. The SPCM is an observational scale of 22 seated postural alignment items and 12 functional movement items, each scored on a four-point, criterion-referenced scale. A secondary purpose of this article is to report the reliability of the seven-point Level of Sitting Scale (LSS). Interrater and test-retest reliability of the SPCM items and the one-item LSS were evaluated on a sample of 40 children with developmental disabilities who sat with and without their seating systems. Kappa values of .75 or higher were considered excellent, .40 to .74 as fair to good, and less than .40 as poor. The interrater reliability tests for the two seated conditions and the two test sessions conducted 3 weeks apart yielded overall item Kappa coefficient means of .45 for the alignment section and .85 for the function section. Test-retest results for the SPCM items were less satisfactory, with item Kappa coefficient means for the two seating conditions and raters of .35 and .29 for alignment and function, respectively. Reliability results did not appear to be consistently better among seating conditions, raters, or test sessions. Kappa coefficients for the LSS were fair to good for both interrater and test-retest reliability. Plans for future development of the SPCM and LSS are discussed.

Adolescent

Interrater reliability of therapists' judgements of graphed data.

Increased emphasis on the use of single-subject designs in physical therapy research suggests the need to examine whether therapists can meaningfully interpret the results of such research as part of the clinical decision-making process. With this goal in mind, the interrater reliability of therapists to make visual judgments from graphed data that included a trend line was examined. Thirty therapists were presented with 24 graphs of single-subject data from AB (baseline-treatment) designs. Each graph included a trend line calculated using the split-middle method of trend estimation. The trend line was computed using the baseline data and then extended into the treatment phase to "predict" patient performance. The analysis, using intraclass correlation coefficients (ICCs), revealed low interrater agreement, with ICC values ranging from .37 to .55 for the entire sample. Evidence is presented that the statistical backgrounds of some raters positively influenced interrater reliability. No statistically significant relationship was found between interrater agreement and visual components of the graphed data, such as changes in slope or variability.

Humans