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Biomedical subjects

D S Brown

Publications and source records attributed to D S Brown.

At least 91 records · Page 5Linked to original sources

Effect of diet composition on protein requirements of children and adults in northern Mexico.

The overall vegetable and animal protein combinations of the diet in Northern Mexico were determined through a dietary population survey. Vegetable sources made up 45% and animal protein was 55% (45V/55A). Further combinations of up to 100% vegetable protein dietary mixtures (100V) were studied to test the sensibility of the variations on protein requirements of pre-school, school children and adults. Diets were analyzed for amino acid composition and in vivo protein digestibility in rats to estimate true protein requirements according to FAO/WHO/UNU (1985). The effect on the pre-school group showed the widest variation with 1.46 g/kg/day in the 45V/55A to 2.63 in the 100V. For the school-aged children and adults the variations were 1.15-1.79 and 0.94-0.84 g/kg/day respectively.

Adolescent↗

New kappa-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus.

The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]-2- [(alkylamino)methyl]piperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]- 2-[[1-(3-oxopyrrolidinyl)]methyl]piperidine (10) possesses high activity in the rabbit vas deferens (LVD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antinociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg, sc). The spirocyclic analogue 8-[(3,4-dichlorophenyl)acetyl]-7-(1-pyrrolidinylmethyl)-1,4-dio xa-8- azaspirol4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

Analgesics↗

Synthesis, antinociceptive activity, and opioid receptor profiles of substituted trans-3-(decahydro- and octahydro-4a-isoquinolinyl)phenols.

A series of trans-3-(6- and 7-substituted-decahydro-4a-isoquinolinyl)phenols and trans-3-(octahydro-4a-isoquinolinyl)phenols have been synthesized as potential opioid analgesics. Using a combination of in vitro and in vivo test systems, the receptor profiles of selected compounds have been assessed and in some instances distinguish between mu- and kappa-receptor agonists. In general, introduction of a 6-exocyclic methylene group into the trans-3-(decahydro-4a-isoquinolinyl)phenol system enhanced both antinociceptive activity and kappa-opioid receptor selectivity. For each series, analogues bearing an N-cyclopropylmethyl substituent exhibited greater kappa-receptor selectivity while N-methyl derivatives showed greater mu-receptor selectivity. The 7-substituted compounds (3b) were significantly less potent antinociceptive agents than their 6-substituted counterparts (3a), the octahydroisoquinoline analogues exhibiting intermediate activity. The axial 8-methyl-6-exocyclic methylene isoquinoline (20) is the most potent compound in the mouse abdominal constriction assay (ED50 = 0.05 mg/kg sc), whereas the equatorial 8-methyl isomer (16) was significantly less potent (ED50 = 3.3 mg/kg sc).

Analgesics↗

Improvement in attitudes toward the elderly following traditional and geriatric mock clinics for physical therapy students.

The purpose of this study was to determine whether the attitudes of students in a physical therapy education program toward the elderly could be influenced positively by (1) having classroom discussion led by an individual with expertise in geriatrics and (2) having only individuals aged 65 years or older participate in a specially designed geriatric mock clinic (GMC). Subjects were 47 first-year students divided into a control group (n = 24) and an experimental group (n = 23). Students in the control group participated in two 4-week clinical rotations. Students in the experimental group participated in one 5-week clinical rotation and in one 3-week GMC. Students in both groups were given a pretest and a posttest administration of the Kogan Old People Scale to assess their attitudes toward the elderly. No significant difference was found between the two groups' overall attitude scores on the pretest or the posttest results. Overall, positive attitude scores increased significantly for both groups, although the increase was greater for the experimental group than for the control group. Negative attitude scores decreased significantly for the experimental group, but did not change for the control group. We concluded that both traditional clinical rotations and a specially designed GMC influenced the students positively. Suggestions have been made for the Clinical Instructor who wishes to influence physical therapy students' attitudes to meet the increasing needs of the elderly patient population.

Adult↗

Effect of the beta-adrenoceptor agonist clenbuterol and phytohaemagglutinin on growth, protein synthesis and polyamine metabolism of tissues of the rat.

1. The kidney bean lectin, phytohaemagglutinin (PHA), induced a marked atrophy of skeletal muscle which was evident from the changes in tissue composition (protein, RNA, DNA and polyamine content) and from the reduction in weight and protein synthesis of hind leg muscles of rats fed on kidney bean-diets for four days. The beta-adrenoceptor agonist, clenbuterol, induced skeletal muscle hypertrophy by transiently stimulating protein synthesis. As a consequence, the muscle loss caused by a short exposure to PHA was, in part, ameliorated by clenbuterol treatment. 2. Cardiac muscle was affected to a lesser extent than skeletal muscle by both clenbuterol and the lectin. However, there was evidence that protein synthesis in heart was reduced by PHA. 3. PHA had opposite effects on the gut, the lectin-induced hyperplasia of the jejunum was accompanied by a large increase in protein synthesis. Clenbuterol alone had no effect on the jejunum whereas a combination of PHA and clenbuterol appeared to exacerbate the effect of the lectin on gut. 4. Both the lectin-induced gut growth and the hypertrophy of skeletal muscle caused by clenbuterol were preceded by the accumulation of polyamines in the respective tissues. Of particular note was the observation that a significant increase in the proportion of the intraperitoneally injected 14C-labelled spermidine or putrescine taken up by the growing tissues could be detected by the second day. Therefore, the measurement of uptake of labelled polyamines may be used as a sensitive indicator of early alterations in tissue metabolism.

Animals↗

Recovery from diffuse traumatic brain injury in Johannesburg: a concurrent prospective study.

Three hundred and twenty-six persons with light, moderate, or severe diffuse traumatic brain injury (TBI) were assessed during initial hospitalization in Johannesburg. One hundred and forty-four were followed up at approximately six months, 83 at 12 months, and 71 at 24 months posttrauma. The sample attrition rate was high. When patients could not be found, data were obtained from their caregivers. Recovery was measured in five different areas of functioning: family relationships, psychologic problems, activities of daily living (ADL), employment status, and physical status. Psychologic problems and family relationships worsened with time, but proficiency in ADL improved; physical and employment status remained relatively stable during the survey period. Severity of injury was significantly correlated with outcome in each functional area at some point in the follow-up period. Discrepancies between patients' and caregivers' perceptions of outcome were noted, particularly in the area of psychologic functioning. Caregivers tended to rate the recovery made by the patient as better than the outcome patients perceived themselves to have made. These differences in perception diminished with time. The multifactorial nature of recovery after TBI is indicated by the improvements seen in some functional areas and the worsening of outcome in other areas. These findings suggest that rehabilitation programs for persons with TBI should (1) include caregivers, (2) focus on the adjustment of both parties to their new circumstances, and (3) facilitate a convergence in their perceptions. Adequately defining recovery is a first step to estimating the prevalence of TBI, but necessitates further work. Epidemiology awaits a better understanding of the recovery process after TBI.

Activities of Daily Living↗

Epidemiology of non-fatal injuries due to external causes in Johannesburg-Soweto. Part II. Incidence and determinants.

A total of 3,535 trauma cases were enumerated in Johannesburg-Soweto between 1989 and 1990 in the course of 271 hospital ward rounds and 43 casualty watches. The overall trauma incidence was 2,886 new cases per annum per 100,000 population, rising to 19,872 for coloured males aged 20 - 24 years and to 8,761 for black males aged 20 - 24 years. Overall the male/female ratio was 2.9 rising to 6 or more in adolescence (15 - 19) for blacks and coloureds. There were some 156 new resident cases of trauma daily; half these were victims of interpersonal violence, and coloureds constituted 22% of this group, although forming only 8% of the denominator population. With regards to cause, most trauma among blacks and coloureds arose from interpersonal violence and significantly less from transport accidents. Among blacks injured in transport accidents (the majority of which involved motor vehicles) most were pedestrians, whereas most whites injured in such accidents were occupants of vehicles. For all groups trauma was most likely to be incurred 'in the street' although for white and coloured women the home was most dangerous. The implications of these and related findings for treatment and prevention and briefly reviewed.

Adolescent↗

Epidemiology of traumatic brain injury in Johannesburg--I. Methodological issues in a developing country context.

Incidence studies in the developing countries present epidemiologists with unique methodological challenges for which novel solutions must be found. These challenges arise from archival inadequacies, hospital overcrowding, high violence rates, and limited research funding that necessitates low cost epidemiology. This paper describes the methods devised in Johannesburg, South Africa, in order to develop incidence estimates of determinable reliability of the morbidity and mortality arising from traumatic brain injury, and its etiology. Results are reported in Part II of the paper (p. 289).

Age Factors↗

Epidemiology of traumatic brain injury in Johannesburg--II. Morbidity, mortality and etiology.

Using the method described in Part I (p. 283), data on the epidemiology of traumatic brain injury (TBI) in Johannesburg are presented. The overall annual incidence of TBI is 316 per 100,000. Data for Africans and Whites show marked contrasts. Among Africans, incidence is 355/100,000, with a male-female ratio of 4.4, and 763/100,000 for males aged 25-44; for Whites, it is 109/100,000 overall, with a male-female ratio of 40.1, and 419/100,000 for men aged 15-24. The overall incidence of fatal TBI is 80/100,000, with a case fatality ratio of 0.20. Interpersonal violence accounts for 51% of nonfatal TBI among Africans, as against 10% for Whites, while motor vehicle accidents cause 27% of African nonfatal TBI and 63% among Whites. Some explanatory hypotheses for this race- and sex-specific skewing of the incidence and causes of TBI are developed.

Adolescent↗

Non-fatal injuries due to interpersonal violence in Johannesburg-Soweto: incidence, determinants and consequences.

A prospective, hospital based sampling procedure conducted between June 8th, 1989 and August 24th, 1990 identified 1592 victims of interpersonal violence in six state and five private hospitals serving the Johannesburg magisterial district (which includes Soweto). For the 1282 victims resident in the area, this corresponded to crude annualised incidence rates per 100,000 population of 3821 for coloureds, 1527 for blacks, 467 for whites, 433 for asians and 1380 for all residents. Males, most of whom were aged 20-24 years, constituted 83.9% of all victims and were most often attacked on the streets. The majority of females were attacked at home by a spouse or lover, and most incidents occurred between dusk and midnight on weekends. Sharp violence was the most frequent type, involving 52.2% of the male and 51.4% of the female victims. Analysis by racial classification of the overall findings for mechanism of injury and relationship to aggressor showed dramatic differences. Limitations of the findings are discussed. After comparison with similar data for two United States cities and Copenhagen, Denmark, it is hypothesised that the racial differences in the present findings reflect the interplay of universal structural determinants and a specific colonial factor rooted in the sociology and psychology of oppression. Some implications of these findings and hypothesised determinants for violence prevention initiatives are mentioned.

Adolescent↗

Polyamide profiles of porcine milk and of intestinal tissue of pigs during suckling.

Previous studies have suggested that luminal polyamines can directly influence intestinal differentiation of neonatal rats. The present investigation has demonstrated the presence of high levels of polyamines in porcine milk and in the intestinal tissues of suckling pigs. The quantities of polyamines in sow's milk sampled between wk 1 and 8 of lactation were determined using high performance liquid chromatography (HPLC). The concentration of milk spermidine (SPD) remained constant over the first 3 to 4 wk of lactation but increased 4-fold between wk 4 and 7. Neither putrescine nor spermine (SPN) were detected in any of the milk samples. During intestinal development the mucosal SPD/SPN ratio was elevated between wk 1 and 3 and wk 5 and 7. The latter period of increase corresponded with the surge in milk SPD concentration. It is suggested that milk SPD is taken up from the intestinal lumen and is involved in potentiating intestinal differentiation during the latter part of the suckling period.

Animals↗

HIV infection in persons with prior mental retardation.

This paper presents five case studies of persons who were mentally retarded prior to infection with human immunodeficiency virus (HIV). Particular emphasis is placed on neuropsychological functioning, and its interaction with management and treatment. The effects of HIV on neurological functioning in such persons has not been previously documented. Although it may be hypothesized that mentally retarded people are at increased risk for developing neurological complications, these preliminary data suggest this is not so and that the development of HIV-related encephalopathy is no different in the mentally retarded, manifesting in the AIDS-related complex (ARC) and AIDS stages of illness. Within the context of HIV infection, the cognitive status of the mentally retarded creates unique treatment and management difficulties, and some guidelines are presented.

AIDS Dementia Complex↗

Effect of fasting and refeeding on basolateral polyamine uptake and metabolism by the rat small bowel.

Fasting reduced the weight, protein, DNA, RNA and polyamine contents of the small intestine of rats, but its effects on the in vivo uptake of intraperitoneally injected 14C-spermidine through the basolateral membrane of the small intestine were small. The uptake of putrescine was nearly doubled by fasting for 48 h. Fasting for 48 h had reduced villus length but was without effects on the crypts. Refeeding for 6 h of rats fasted for 48 h led to hypertrophic growth: the length of both crypts and villi increased by about 50% without changes in cell number. The uptake of spermidine by the small intestine increased above not only that in fasted rats but also that in the controls fed ad libitum. The high putrescine uptake of rats fasted for 48 h was unchanged after refeeding for 6 h, but returned to control values after 12 h. Spermidine in the gut was well conserved, while most of the putrescine was transformed into non-polyamine metabolites. It is concluded that refeeding stimulates basolateral spermidine uptake, and this may be a general mechanism for polyamine accretion in adaptive growth of the small intestine.

Animals↗

Luminal and basolateral polyamine uptake by rat small intestine stimulated to grow by Phaseolus vulgaris lectin phytohaemagglutinin in vivo.

Luminal and basolateral uptake of polyamines by the rat small intestine was studied in vivo. In the concentration range studied (0.1-5 mg per rat) 23-47% of the individual polyamines given intragastrically were found in the body after 1 h, with the small intestine retaining 4-12% of the dose. With spermidine or spermine, labelled polyamines accounted for 85-96% of the counts in the small intestine and between 72-82% were in the form given. However, with putrescine only 29-39% of the label found in the tissue remained in polyamine form and even less, 11-15%, as putrescine. Luminal uptake of polyamines was linear, non-saturable and was not stimulated when small intestinal growth was stimulated by phytohaemagglutinin (PHA). On the basolateral side of the gut, polyamine uptake was stimulated by PHA in a time-dependent way in advance of detectable growth. Overall polyamine recoveries were high (89-99%) with intraperitoneally administered spermidine and spermine. Moreover, a large proportion of the counts in the tissue (63-89%) were still in the original form. Even with putrescine, total recoveries of polyamines (72-88%) and putrescine (24-33%) were elevated in comparison with those from the lumen. Treatment of rats with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduced tissue polyamine content, although it had slight effects only on basolateral polyamine transport. The PHA-stimulated increase of polyamine uptake was not abolished in the presence of DFMO.

Animals↗