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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
PubMed2001

Relaxin decreases renal interstitial fibrosis and slows progression of renal disease.

BACKGROUND: Relaxin, a hormone of the insulin-growth factor family, promotes collagen remodeling. In rodent models of pulmonary and dermal fibrosis, relaxin reduced interstitial fibrosis. To study relaxin's effect in renal disease, we used the experimental bromoethylamine (BEA) model that leads to severe renal interstitial fibrosis, a decrease in glomerular filtration rate, and albuminuria at one month. METHODS: Rats were injected with BEA one week prior to implantation of an osmotic pump delivering relaxin (2 microg/hour) or vehicle continuously for 28 days. RESULTS: BEA caused a significant decrease in creatinine clearance, which was partially prevented by relaxin. In the relaxin-treated BEA rats, serum creatinine was normal, and albumin excretion was slightly decreased. By morphometric measurement, relaxin administration was associated with a significant decrease in interstitial fibrosis at the corticomedullary junction. This was accompanied by a decrease in the number of ED-1 positive cells (an index of macrophage infiltration) and in the intensity of immunohistochemical staining for transforming growth factor-beta. This antifibrotic effect of relaxin did not appear to be mediated by systemic hemodynamic changes since the mean arterial pressure was not significantly different among the groups. CONCLUSIONS: Relaxin may have a useful application in decreasing interstitial fibrosis and thereby slowing the progression of renal disease.

Animals↗
PubMed2001

Differential effects of enalapril and irbesartan in experimental papillary necrosis.

This study was undertaken to determine whether angiotensin receptor blockers are as renoprotective as angiotensin-converting enzyme inhibitors in an experimental model of chronic interstitial renal disease. Groups of rats received one of the following treatments for 1 week: (1) enalapril, (2) diltiazem, (3) a cocktail of hydralazine, reserpine, and hydrochlorothiazide, or (4) irbesartan (an AT1 antagonist). The animals were injected with bromoethylamine (200 mg/kg), and antihypertensive treatment continued for 1 month. All drugs were effective in lowering the mean arterial pressure. The bromoethylamine-treated rats developed albuminuria and sustained a 40-50% decrease in creatinine clearance. Enalapril and irbesartan reduced albuminuria, but only enalapril partially prevented the decline in creatinine clearance and lowered the number of ED-1-positive cells. Diltiazem and cocktail had no effect on proteinuria, creatinine clearance, or ED-1 cells. In this experimental model, the effects of enalapril and irbesartan were not identical. Both drugs reduced proteinuria, but enalapril was more effective in protecting the renal function. The fact that the AT1 antagonist protected against albuminuria but did not affect the clearance of creatinine implies that the results seen with angiotensin-converting enzyme inhibition may be in part due to an effect on angiotensin II via AT2 receptor blockade or through an effect on bradykinin.

Angiotensin Receptor Antagonists↗
PubMed2000

Sexuality in persons with lower extremity amputations.

PURPOSE: There is a paucity of information regarding sexual functioning in persons with lower extremity amputations. The purpose of this study was to describe sexual and psychological functioning and health status in persons with lower extremity amputation. METHODS: Self-report surveys assessed sexual functioning (Derogatis Inventory), depression (Beck Depression Inventory, anxiety (State-Trait Anxiety Inventory), and health status (Health Status Questionnaire) in a convenience sample of 30 men with lower extremity amputations. Mean age of the participants was 57 years (range 32-79). Mean duration since amputation was 23 months (range 3-634 months). Twenty one subjects (70%) had trans-tibial and seven subjects (23%) had trans-femoral amputations. RESULTS: A majority of subjects were experiencing problems in several domains of sexual functioning. Fifty three percent (n = 16) of the subjects were engaged in sexual intercourse or oral sex at least once a month. Twenty seven percent (n = 8) were masturbating at least once a month. Nineteen subjects (63%) reported orgasmic problems and 67% were experiencing erectile difficulties. Despite these problems, interest in sex was high in over 90% of the subjects. There was no evidence of increased prevalence of depression or anxiety in these subjects when compared to other outpatient adult populations. CONCLUSIONS: Sexual problems were common in the subjects studied. Despite these problems, interest in sex remained high. Few investigations have been directed toward identifying the psychological and social factors that may contribute to these problems and more research with a larger population is needed in this area.

Adaptation, Psychological↗
PubMed2000

Pressure ulcer risk in spinal cord injury: predictors of ulcer status over 3 years.

OBJECTIVE: To identify predictors of pressure ulcers in men with spinal cord injury over a 3-year period. DESIGN: Longitudinal, two-panel, cohort. SETTING: Community. PARTICIPANTS: One hundred eighteen men with spinal cord injury. MEASURES: Interviews, questionnaires, and physical examinations were completed in two phases, 3 years apart. Information obtained included demographic and spinal cord injury characteristics; ulcer history; health beliefs and practices; measures of impairment, disability, and handicap; and skin integrity. RESULTS: Thirty-one percent of the participants reported having a pressure ulcer in the 12 months before Phase 2. Some Phase 1 predictors of self-reported ulcers in the year before Phase 2 were a younger age at onset of spinal cord injury, previous pressure ulcer surgery, and the presence of a pressure ulcer in the year before Phase 1. On examination at Phase 2, 59% presented with an ulcer. Phase 1 predictors of ulcer presence at Phase 2 examination were similar to predictors for self-reported ulcers. CONCLUSION: Individuals with the identified predictive characteristics are at greater risk for developing pressure ulcers. These individuals should receive additional interventions to reduce that risk. Potential interventions include more systematic and frequent follow-up, frequent review of pressure ulcer prevention and management strategies, and provision of needed personal assistance and relevant equipment.

Activities of Daily Living↗
PubMed1999

Evolution of experimentally induced papillary necrosis to focal segmental glomerulosclerosis and nephrotic proteinuria.

Bromoethylamine (BEA)-induced papillary necrosis is a reproducible model for analgesic nephropathy. We induced this lesion in groups of male Sprague-Dawley rats and followed the functional and histological changes for 1 year. We found that by 1 month, necrosis of the papilla was complete, glomerular filtration rate was depressed, and urine albumin excretion was increased. There was an extensive interstitial fibrosis characterized by a mononuclear cell infiltrate and patchy tubular atrophy. By 6 months, there was re-epithelialization of the papillary stump accompanied by a marked increase in albuminuria and an improvement in concentrating ability. Changes seen at 9 months were more advanced. There was extensive cortical fibrosis manifested by pitting of the surface of the kidney. At 1 year, renal function remained impaired (creatinine clearance reduced by 65% to 0.26 mL/min/100 g), and the animals were now markedly nephrotic, with albuminuria of 254 mg of albumin/24 h. In the BEA rats, there was selective destruction of the deep nephrons leading to an increase in the volume-ratio of superficial to deep nephrons. Glomerular changes, affecting approximately 60% of the glomeruli, were characteristic of focal segmental glomerular sclerosis. This model of papillary necrosis/interstitial fibrosis is associated with chronic renal insufficiency and leads to the development of focal glomerular sclerosis and nephrotic proteinuria by 6 to 12 months after its induction.

Animals↗
PubMed1999

Changes in collagenases and TGF-beta precede structural alterations in a model of chronic renal fibrosis.

BACKGROUND: To study the role of collagenases and transforming growth factor-beta (TGF-beta) in the genesis of interstitial fibrosis, we used the model of bromoethylamine (BEA)-induced papillary necrosis, which is known to lead over a period of 1 to 12 months to interstitial fibrosis and renal insufficiency. METHODS: Rats were injected with BEA, and urine and kidney tissue (cortex and medulla) were collected after 1, 2, 3, 7, and 30 days. One kidney was perfused and fixed for morphological studies and immunostained for collagen type I, III, and IV. The other kidney was used to prepare cortex and medulla extracts for gelatinases (by fluorometric and zymographic techniques), tissue inhibitors of metalloproteinase-1 (TIMP-1), and TIMP-2 (by enzyme-linked immunosorbent assay, ELISA) and TGF-beta1 (by ELISA). RESULTS: Albuminuria and interstitial fibrosis were present in BEA rats by day 7, which continued until day 30. Immunocytochemical staining for collagen types showed that collagen III and IV increased in the interstitium by day 30, but collagen I remained unchanged. Gelatinase activity in the medulla decreased by 57% compared with control by day 2 and remained low until day 30. In the cortex, gelatinase activity remained unchanged between 0 and 7 days after BEA but decreased by 72% by day 30. TIMP-1 and TIMP-2 were decreased by 80% compared with day 0 in both the medulla (by day 1) and cortex (by day 2) and remained low up to day 30. TGF-beta1 immunoreactivity increased progressively until day 2 in the medulla (16-fold higher than control) and day 3 in the cortex (8-fold higher than control) and returned to control level by day 3 in the medulla and by day 30 in the cortex. Two days after BEA injection, the mRNA for TGF-beta1 was increased eightfold in the cortex and 12-fold in the medulla, and it remained high for up to 30 days. CONCLUSIONS: The fibrosis that follows papillary necrosis is associated with both high TGF-beta1 expression and depressed gelatinolytic activity.

Animals↗
PubMed1998

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1991

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↗
PubMed1990

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↗