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.

Persistence of the immunoprotective effects of leukemia X fibroblast hybrid cells toward leukemia in histocompatible mice.

Hybrids of ASL-1 murine leukemia cells and LM(TK-) cells, a cultured line of mouse fibroblast origin, stimulate partial immunity toward ASL-1 cells in (A/J X C3H/HeJ)F1 mice (F1 mice). Such mice ordinarily exhibit no resistance to the malignant proliferation of ASL-1 cells. Unprotected animals invariably die within 14-18 days after receiving as few as 200 ASL-1 cells. The hybrid cells, the mice used in the experimental studies and the leukemia cells used for challenge all share the same histocompatibility antigens. ASL-1 cells are H-2a; LM(TK-) cells are H-2k, both ASL-1 X LM(TK-) hybrid cells and A/J X C3H/HeJ)F1 mice are H-2a/k. The long-term persistence of the immunoprotective properties of the hybrid cells toward murine leukemia was investigated by using cells that had been in continuous culture for approx. 36 months. (A/J X C3H/HeJ)F1 mice injected previously with hybrid cells in continuous culture and then challenged with up to 10(7) ASL-1 cells survived longer (p less than 0.001) than mice who had not received hybrid cells previously. Some mice challenged with lesser number of ASL-1 cells survived indefinitely (greater than 200 days). The median survival time of F1 mice injected simultaneously with 10(7) hybrid cells and 200 or 2000 ASL-1 cells was significantly (p less than 0.001) prolonged as well, although the differences between experimental and control groups are less pronounced than if the hybrid cells were injected before challenge with ASL-1 cells. The hybrid cells like those freshly prepared continue to be rejected by histocompatible precipients. In no instance has there been evidence of a progressively growing tumor of hybrid cells in immunocompetent F1 mice. Hybrid cells like those investigated previously do form rapidly growing metastasizing tumors in immunodeficient nu/nu (BALB/c) or X-irradiated (550 R) F1 mice. The cells possess approx. 70 chromosomes (reduced from 85) including chromosomes identified as having originated in each parental source. Like (A/J X C3H/HeJ)F1 animals, they continue to express both H-2a and H-2k antigenic determinants.

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.

Light-dark and feeding regimens affect circadian phasing of blood-ethanol decay rates.

Rats maintained on a 12 hour:12 hour light-dark cycle, with food continuously available, exhibited a prominent and reproducible circadian rhythm in the slope of the linear blood-ethanol clearance curve. Peak values fell near the end of the dark period and trough values late in the light period. These phase relationships persisted with 4, 8 and 12 hours phase shifts of the illumination schedule. However, when food availability was restricted to 4 hours per day the feeding regimen became the dominant synchronizer for the rhythms in blood-ethanol decay rate and body core temperature. With resumption of the ad lib feeding regimen, the L-D cycle again entrained these rhythms. Ethanol injections (1.5 g/kg, IP) did not alter the expected excursion of the circadian temperature curve, as measured 4 hours after dosing.

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.

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.

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.

A classification of wheelchair seating.

Selecting a wheelchair cushion for a person with a physical disability can be confusing and difficult. Because many cushions are commercially available and because no single cushion will work for all patient categories, the therapist needs to be aware not only of the factors that influence the selection of the cushion such as patient activity level and lifestyle, but also of the differences that exist among all the cushions she or he might recommend.

Wheelchair cushions: a historical review.

An important objective of occupational therapy practice is to maximise functional potential in patients who have physical disabilities. Pressure sores are a major complication in the medical course of these individuals. Therefore, prevention, or at least the proper management, of these sores becomes an important focus for occupational therapists who treat the physically disabled patient. Occupational therapists often prescribe wheelchair cushions to relieve pressure and reduce the risk of ulceration. Unfortunately, occupational therapy literature offers few articles dealing with this significant problem. This paper presents a historical review of wheelchair cushions and details some of the physiological and clinical research efforts that are the basis of prescription practice today.

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.

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.

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.

A system for clinically evaluating wheelchair pressure-relief cushions.

Pressure-related decubitus ulcers are a frequent disability and life-threatening complication in the management and rehabilitation of patients with spinal cord injuries. This paper describes a system developed to quantitate and evaluate a patient's response to wheelchair pressure-relief cushions. Maximum pressure and the tissue pressure distribution on six varieties of wheelchair cushions were determined for a sample of 57 patients with a history of decubitus ulcers. Wide variations in (mean) maximum pressure were observed. However, even greater variations were found in the distribution (bony/soft tissue) of the pressure. These data demonstrate that no single cushion was clearly superior in relieving pressure for all patients. Therefore, individualization of wheelchair cushions for each patient may be essential in order to minimize the probability that the person will experience a tissue-pressure problem.

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.

Custom selection of support surfaces for wheelchairs and beds: one size does not fit all.

Support surfaces aid in preventing pressure sores and trauma, correct posture, and provide patient comfort. Knowing how to custom select a support surface is vital for meeting the patient's protective, postural, and pain-prevention needs.

Wheelchair cushion modification and its effect on pressure.

Prevention of pressure sores is a major objective in the rehabilitation of individuals with paraplegia and quadriplegia. Wheelchair cushions made of polyurethane foam are frequently prescribed to relieve pressure and reduce the risk of ulceration for persons seated in wheelchairs. Because no cushion uniformly distributes pressure for all diagnostic groups, it may become necessary to modify a commercial cushion to provide protection against the effects of pressure. In this study, foam wheelchair cushions were geometrically modified by removing wedges from their wheelchair contacting side to reduce ischial pressure. Ischial pressures of 30 subjects on one unmodified and five geometrically modified cushions were determined using the Pressure Evaluation Pad. No significant differences were determined in the pressure measured for one modified cushion compared to the other modified cushions or for the control cushion. Independent effects of subject sex, diagnosis, and body build could not be identified so that no optimal modification was noted for any subpopulation of the total patient group. Marked individual variation and responsiveness were noted between cushions for any given patients. These data demonstrate that individualization of the prescription of a wheelchair cushion is essential for optimal pressure relief, and that no cushion appears to be universally superior for all patients or for any subgroup of patients requiring pressure relief devices.

Meal timing dominates the lighting regimen as a synchronizer of the circadian blood ethanol clearance rate rhythm in rats.

The effects of timing of a single daily meal on the circadian rhythm of blood ethanol clearance rates were investigated in two groups of rats maintained on opposite 12 hours light: 12 hours dark (LD) schedules. Initially, the rats were fed ad libitum. Then feeding was restricted to 4 mid-light (ML) hours for one group and 4 mid-dark (MD) hours for the other. Finally, the meal timing was reversed; the ML-fed group became the MD-fed group and vice versa. Following acclimatization to each of the 3 feeding regimens, blood ethanol clearance rats ere determined for subgroups (n - 8) of both groups injected (i.p.) with ethanol at 5 times during 24-hour spans. The LD schedule synchronized the clearance rate rhythm during ad libitum feeding. Although the rhythm persisted without significant amplitude changes during restricted feeding regimens, minimal clearance rates during ML and MD feeding approximately the time of food presentation, with maximal rates 8-12 hours later. This relationship remained constant with the feeding phases were reversed. Thus, when food availability is limited, the single daily mean dominates the lighting regimen as synchronizer of the circadian blood ethanol clearance rate rhythm.

Circadian rhythms of alcohol dehydrogenase and MEOS in the rat.

The circadian peak in alcohol dehydrogenase (ADH) activity fell near the time of maximal blood ethanol clearance rates both in groups of rats injected with a single ethanol dose (acute group) and in rats continuously exposed to ethanol for 22 weeks (chronic group). However, at all timepoints investigated ADH activity levels were lower and fluctuated less in the chronic group than in either the acute or control (ethanol naive) groups. In contrast, activity levels of the microsomal ethanol oxidizing system (MEOS) revealed a prominent rhythm that was 180 degrees out of phase with the ADH rhythm in the chronic group, while MEOS activity showed very low levels in the acute and control groups and did not vary over the circadian span.