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Biomedical subjects

S L Garber

Publications and source records attributed to S L Garber.

At least 19 recordsLinked to original sources

Angiotensin-converting enzyme inhibition reduces the effect of bromoethylamine-induced papillary necrosis and renal fibrosis.

Rats injected with a single, 50-mg dose of bromoethylamine (BEA) developed papillary necrosis accompanied by sever interstitial fibrosis. At 1 mo, the creatinine clearance decreased (control 0.66 versus BEA 0.33 ml/min per 100 g body wt, P = 0.02), and the urine albumin-to-creatinine ratio increased markedly (control 0.19 versus BEA 0.51, P = 0.02). In a group of animals given the angiotensin-converting enzyme inhibitor enalapril (Enal; 100 mg/L) in their drinking water for 4 wk, beginning 1 wk before BEA injection, creatinine clearance improved significantly (BEA 0.33 versus Enal + BEA 0.52 ml/min per 100 g body wt, P = 0.01) and albumin excretion fell to zero. Histologic examination revealed an 88% decrease in the area of papillary necrosis and a decrease in the degree of interstitial fibrosis in the corticomedullary junction. To determine whether this was due to changes in urine flow rate induced by enalapril, a group of animals was injected with BEA, and enalapril at the above dose was begun 1 wk later. After 1 mo, the enalapril-treated animals showed the same improvement in creatinine clearance (BEA 0.33 versus BEA + Enal 0.50 ml/min per 100 g body wt, P = 0.03) and suppression of albumin excretion. The area of papillary necrosis was reduced by 67%. In the BEA animals treated with enalapril, ED-1-positive cells, alpha-smooth muscle actin, and transforming growth factor-beta1 were decreased compared with BEA alone. It is concluded that in this model of papillary necrosis, enalapril protects renal function and decreases interstitial fibrosis mediated at least in part through an angiotensin II/bradykinin-dependent mechanism.

Albuminuria

Reported pressure ulcer prevention and management techniques by persons with spinal cord injury.

OBJECTIVE: The purpose of this study was to identify factors that resulted in severe pressure ulcers in a community-based sample of 23 persons with spinal cord injury (SCI). DESIGN: A correlational design was used. SUBJECTS: Twenty men and three women, 57% with tetraplegia and 43% with paraplegia, participated. Adult participants with an ulcer of 12 weeks' duration or less were recruited from the plastic surgery clinic of a regional SCI center. MEASURES: A structured survey assessed demographic, SCI and ulcer characteristics; detection method; immediacy and appropriateness of action; time from detection to clinic visit; number of prior ulcers; and knowledge and practice of ulcer prevention techniques. Ulcer characteristics (ie, location, size, and stage) were assessed by examination and compared with participants' descriptions of their ulcers. RESULTS: Severe ulcers and ulcers that progressed in severity after initial detection were less accurately described by participants. Individuals who waited longer to come to the clinic presented with more severe ulcers. Taking immediate or appropriate action when an ulcer was detected was related to reported performance of more preventive behaviors. Contrary to expectation, immediacy and appropriateness of action, and knowledge and practice of preventive behaviors were unrelated to severity, progression of severity, and time from detection to the clinic visit. The findings suggest that educational programs should emphasize more strongly immediate visits to a physician upon detection of an ulcer. Furthermore, such educational models should be assessed for their effectiveness in reducing ulcers and preventing progression in severity once persons with SCI return to the community.

Adult

Effect of acute and chronic glutathione depletion on renal function in the rat.

Renal function was evaluated in normal and acid-loaded rats following acute and chronic depletion of glutathione (GSH) by buthionine sulfoximine (BSO). Creatinine clearance and fractional excretion of electrolytes were normal. There was no acidification or concentration defect detected in animals with acute or chronic GSH depletion.

Ammonium Chloride

Xanthopterin-induced renal dysfunction: a reversible model of crystal nephropathy.

Xanthopterin (XPT), an unconjugated pteridine compound, affects cell growth and differentiation. When injected into rats, XPT has caused changes that have been interpreted as renal growth and hypertrophy. In the present study, we investigated the effect of intraperitoneal administration of XPT on the renal function in the rat. XPT administration was associated with polyuria and a reversible form of nonoliguric acute renal failure (ARF), with renal function declining maximally after 2 days and returning to normal after 7 days. The polyuria was due, at least in part, to a concentrating defect that was vasopressin resistant. The ability of XPT to induce ARF was modulated by dietary salt intake, being enhanced by a low-sodium diet and prevented by a high sodium intake. Histological examination of the kidneys showed intratubular crystal deposition and acute tubule necrosis, suggesting that XPT induces crystal nephropathy. There was an increase in wet and dry weights of the kidney and an increased DNA/protein ratio, compatible with a hyperplastic response. Because the severity of other crystal nephropathies may be modulated by urine flow rate and pH, we studied the ability of water diuresis or alkaline diuresis to protect against XPT-induced ARF. Both water diuresis and HCO3 loading blunted the ability of XPT to decrease renal function. The change in renal function induced by XPT in the various groups was paralleled by corresponding changes in the levels of XPT-like substances in the kidney and by the amount of crystal deposition. Thus, XPT injection induces crystal nephropathy, the severity of which can be modulated by dietary salt intake, urine pH, and urine flow rate.

Acute Kidney Injury

Prospective study of pressure ulcer risk in spinal cord injury patients.

Sixty men with spinal cord injury who had developed pressure ulcers in the past but whose skin was intact when they joined the study were followed for 2 years, or until a pressure ulcer developed. Forty of the men were contacted every 4-6 weeks to answer questions about their skin care practices and to provide a 24 hour urine sample. The others were only contacted at the beginning and the end of the study to answer a questionnaire and to provide a urine sample. Changes in skin collagen metabolism were monitored by measuring urinary excretion of a metabolite, glucosyl-galactosyl hydroxylysine (glu-gal Hyl), corrected for creatinine excretion. Sustained increases in levels of glu-gal Hyl excretion were detected at least 2 months and as much as 5 months in advance of overt clinical signs of ulcer development. Increased excretion of glu-gal Hyl was significantly associated (p < 0.05) with the development of a pressure ulcer. An increase in the urinary excretion of glu-gal Hyl is an indication of increased degradation of skin collagen. Body mass index (weight/height2) of 33% of subjects with pressure ulcers, and 12% of those without, was at least one standard deviation below the mean of all subjects. Thirty-six percent of those who smoked developed ulcers, while only 26% of the nonsmokers did.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Differential effect of xanthopterin and biopterin on cell growth.

1. Xanthopterin inhibited proliferation of primary renal proximal tubule cells (RPTC) and LLC-PK1 cells while in a growth phase but when incubated at confluence the cells were relatively insensitive. 2. The growth of malignant human prostate PC-3 cells was also inhibited by xanthopterin in a concentration and time dependent manner. 3. Dunning R3327 AT-3 rat prostate tumor cells which were exposed to xanthopterin in vitro before their in vivo inoculation resulted in smaller tumours while in vivo administration of xanthopterin following implantation also resulted in smaller tumors. 4. Xanthopterin exerts differential effects on cell growth dependent upon the cell origin and their state of proliferation.

Animals

Pressure ulcers in community-resident persons with spinal cord injury: prevalence and risk factors.

The prevalence and correlates of pressure ulcers in terms of their number, severity, and anatomical location were studied in a community-based sample of 100 men and 40 women with spinal cord injury. Thirty-three percent (n = 46) presented with one or more ulcers of at least one stage I severity when visually examined. Twenty-one individuals had more than one ulcer, the maximum number of ulcers being seven. Of 87 ulcers for which severity ratings were available, 30 (34.5%) were stage I, 33 (37.9%) were stage II, and 24 (27.6%) were either stage III or IV. Individuals with an ulcer exhibited more paralysis and were more dependent on others in activities of daily living. A greater proportion of blacks had more severe ulcers (stages III and IV) than their white counterparts. Persons with more severe ulcers incurred their injury later in life, and had significantly lower mean scores on the Occupation and Mobility dimensions of the Craig Handicap Assessment and Reporting Technique. The findings suggest that factors governing initial development of a pressure ulcer differ in part from those responsible for an ulcer progressing in severity.

Adult

Wheelchair cushions for persons with spinal cord injury: an update.

Occupational therapists frequently prescribe wheelchair cushions to reduce the risk of pressure sores in patients with spinal cord injury. In an earlier study (Garber, 1985b), Roho cushions were prescribed for the greatest number of subjects studied. The present study of 197 subjects updates these data and describes current prescription patterns, the use of cushions over time, satisfaction with prescribed cushions, and the occurrence of pressure sores with prescribed cushions. The study shows that the Jay cushion was prescribed most frequently for the current subjects, although it was not recommended for all persons with spinal cord injury. In the second phase of the present study, involving 30 subjects, 30% of the subjects discontinued use of the prescribed cushion. Skin breakdown and the discovery of alternative solutions were given as primary reasons. There was no significant difference in the incidence of pressure sores between subjects who continued to use their prescribed cushions and those who did not. This research supports the conclusion of earlier studies that no one wheelchair cushion is universally effective for all persons and that individual evaluation and routine reassessment are essential in reducing the occurrence of pressure sores.

Beds

Upper extremity assistive devices: assessment of use by spinal cord-injured patients with quadriplegia.

Upper extremity assistive devices prescribed during the rehabilitation of the patient with quadriplegia often are discarded once the patient leaves the hospital. Therefore, we conducted this study to investigate patterns of the prescription and use of such devices and satisfaction with them. An oral questionnaire was administered to 56 spinal cord-injured quadriplegic patients 1 and 2 years after their first rehabilitation experience. Although the patients had discarded 46% of the devices within the 1st year, most of these devices were inexpensive, commercially available devices or devices made by occupational therapists. The respondents' most frequently cited reasons for discarding a device were "improved physical function" and "alternative solutions found." The devices retained in use most often were the more costly orthotics such as reciprocal orthoses and ball-bearing feeders. Sixty-four percent of the devices used within the 1st year were still being used at the end of the 2nd year. Thirty-five percent of all devices prescribed during rehabilitation were still in use at the end of 2 years. The results of this study have heightened therapists' awareness of the efficacy and use of upper extremity assistive devices and have enabled them to eliminate some devices, to modify methods of instructing patients in the use of devices, and to develop alternative products.

Activities of Daily Living

Circadian rhythm of blood ethanol clearance rates in rats: response to reversal of the L/D regimen and to continuous darkness and continuous illumination.

Phase relationships of the circadian rhythms of blood ethanol clearance (metabolic) rates and body temperature were studied in rats successively exposed to 4 illumination regimens: LD (light from 0800-2000 hr), DL (light from 2000-0800 hr), constant darkness (DD) and, lastly, constant light (LL). After a 4-wk standardization to each regimen, body temperatures were taken at 9 X 4-hr intervals to establish baseline circadian profiles. One week later, groups (N = 8) received 1.5 g/kg ethanol (i.p.) at 6 equally spaced timepoints during a 24-hr span, when temperatures were again measured. Ethanol clearance rates were estimated from decreasing blood ethanol levels sampled every 20 min from 60-200 min after dosing, and the resultant elimination curves were subjected to cosinor analysis. These studies show for the first time that the high amplitude circadian rhythm in ethanol metabolism persists under constant conditions of illumination (DD and LL), demonstrating that it may well be a truly internal circadian rhythm and not a response to exogenous cues of the light/dark cycle. During both LD and DL, maximal and minimal ethanol clearance rates fell near the end of the dark and light phases, respectively, and followed circadian peak and trough control temperatures by approximately 6 hr. A fixed internal phase relationship between the core body temperature and the circadian rhythm in ethanol metabolism is demonstrated, thus establishing the rhythm in body temperature as a suitable and convenient internal marker rhythm for studies of the metabolism of low-to-moderate ethanol doses. These studies demonstrate that the phase relationships of blood ethanol clearance rate and body temperature can be manipulated by the illumination regimen selected, an observation of both basic and practical importance.

Animals

Regulation of tryptophan hydroxylase activity by a cyclic AMP-dependent mechanism in rat striatum.

Evidence is presented indicating that a cAMP-dependent mechanism activates tryptophan hydroxylase (TrpH), the rate-limiting enzyme for serotonin (5-HT) biosynthesis. Forskolin, a selective activator of adenylate cyclase, stimulated 5-HT formation in synaptoneurosome preparations of rat striatum, substantia nigra, hypothalamus, and amygdala. Further studies of striatum revealed that the forskolin-induced activation of serotonin synthesis is readily reversible. Also, it may be self-limited by a mechanism of desensitization, since after an initial exposure to forskolin followed by removal, a re-exposure of synaptoneurosomes to forskolin was no longer stimulatory. In contrast to these results for 5-HT synthesis, forskolin-induced stimulation of dopamine synthesis persisted following removal of forskolin; hence the response was not rapidly reversible or desensitized. In soluble extracts of striatum, 8-thiomethyl-cyclic AMP enhanced TrpH activity, supporting a direct role of cyclic AMP and cyclic AMP-dependent protein kinase in regulating TrpH. In agreement with previous reports, 8-thiomethyl cyclic AMP also stimulated tyrosine hydroxylase activity in soluble striatal extracts. We conclude that cyclic AMP is an important regulator of TrpH, in addition to its known effects on tyrosine hydroxylase.

Animals

High-level quadriplegia: an occupational therapy challenge.

Rehabilitation of the C1 to C4 quadriplegic person is a relatively recent phenomenon. Few rehabilitation facilities accept the challenge these patients present. This paper describes a comprehensive occupational therapy program for the C1 to C4 quadriplegic person. It presents the objectives and mechanisms for treating these individuals (e.g., range of motion, strengthening existing musculature, functional activities training, pressure sore prevention, and equipment prescription) and introduces new approaches to increasing function through current therapeutic and engineering technological advances. The quality of life of these patients may well be determined by their exposure to functional activities in occupational therapy.

Humans

Wheelchair cushions for spinal cord-injured individuals.

Pressure sore prevention is a major objective in the rehabilitation of individuals with spinal cord injury. Wheelchair cushions are frequently prescribed to relieve pressure and reduce the risk of pressure sores in this population. In this study, 251 subjects with paraplegia and quadriplegia were evaluated to decide which wheelchair cushions were suitable. Criteria for the comparative evaluation of cushions included not only magnitude and distribution of pressure but also factors such as wheelchair compatibility, ease of transfer, activities, and independence. Although the Roho cushion was prescribed most frequently, it was not recommended for all subjects. This study provides additional evidence that no single cushion is optimal for all people with spinal cord injury. Rather, objective measurements and clinical judgments are essential elements of a complete evaluation.

Equipment Design