Biomedical subjects
S L Garber
Publications and source records attributed to S L Garber.
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.
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.
New perspectives for the occupational therapist in the treatment of spinal cord-injured individuals.
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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.
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.
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.
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.
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.
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.
The effectiveness of preventive management in reducing the occurrence of pressure sores.
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Body build and its relationship to pressure distribution in the seated wheelchair patient.
The clinical evaluation of wheelchair cushions used to relieve pressure of patients with severe physical disability has become a major concern for the rehabilitation team. This paper describes the effects of body build, based on height, weight, sex, and age of the subjects studied, on the location, magnitude and gradient of the pressure exerted by patients seated in wheelchairs. It was found that thin patients had higher pressures over bony prominences and greater frequency of the maximum pressure occurring in a bony location than did average-weight or obese subjects.
Effect of experimental glomerulonephritis on the cells in canine renal lymph with special reference to the veiled cell.
An immunological glomerulonephritis was induced in dogs by the administration of rabbit anti-canine glomerular serum (1 mg/kg) and the effects on white cells in blood, thoracic duct lymph and peripheral renal lymph were observed over 14 days. The principal response was seen in the renal lymph which showed, within 1 hr of the injection of antiserum, a significant increase in its cellular content that lasted for approximately 16 hr. The cells affected by this early response were phagocytic, being both mononuclear and polymorphonuclear. Although the number of lymphocytes leaving the kidney did not increase, the character of these cells changed. Thus, during the first day there was a comparative increase in the number of large lymphocytes, and cells undergoing mitosis appeared in the lymph. These changes suggested the presence of local blast transformation. Later in the course of the response the proportion of small lymphocytes increased and that of large lymphocytes declined. Non-lymphocytic mononuclear cells with characteristics of 'veiled' and 'frilly' cells appeared in renal lymph on the first day and persisted throughout the 14 days. Many of these cells formed the centres of lymphocyte rosettes. The presence of these cells, which have previously been associated with Langerhans cells in the skin, in renal lymph suggests that they have a wide distribution in the body and that they are important during the immunological response to glomerulonephritis.
Trochanteric pressure in spinal cord injury.
Pressure-induced tissue breakdown is a frequent and life-threatening complication for individuals with spinal cord injury. These patients are frequently positioned on their sides to relieve back and sacral pressure while they are in bed. This position causes high trochanteric pressure with the potential for the development of pressure ulcers. In addition, the individual with a spinal cord injury has accompanying absent or diminished sensation, and therefore is not aware of the pressure overload. In this study the positions that will reduce the possibility that trochanteric ulcers will develop are identified. The Pressure Evaluation Pad (PEP), a pneumatic pressure monitoring system, has been used to study the effect of different leg positions on trochanteric pressure. The pressure under the right trochanter was monitored as the contralateral leg was positioned in various degrees of hip and knee flexion or extension. The procedure was repeated for the left trochanter. A study of 50 subjects demonstrated that a position of 30 degrees hip flexion and 35 degrees knee flexion (with lower leg behind midpoint of the body) produced lower contralateral trochanteric pressure than the traditional position of hip and knee flexion across the body. Additionally, thinner patients were found to have higher trochanteric pressure than average weight or obese subjects. Standardizing a method for the positioning of patients on their side can be a significant deterrent to the tissue erosion that greatly interferes with the rehabilitation process.
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.
Fundamentals for ethanol chronopharmacokinetics in nonstarved, serially sampled rats.
Fed versus starved rats were investigated for an appropriate model for studying the chronopharmacokinetics of ethanol. A serially independent dosage-sampling regimen was compared with a serially dependent one. Before beginning the pharmacokinetic studies, a number of experimental pharmacologic variables was systematically examined and quantified. When 24-hour starved rats (LD = 12:12 h) were injected intraperitoneally with ethanol at varying intervals during a single 24-hour period in a serially dependent manner, no significant differences in blood-ethanol clearance rates were observed. However, when the same dose was administered to ad-libitum-fed rats in a serially independent study, a prominent circadian rhythm in clearance rates was revealed. Interindividual variance was less with fed rats than with starved ones. These studies indicate that further characterization of this rhythm should employ ad-libitum-fed rats colony (serially independently) sampled.
A simultaneous comparison of the cells of blood, renal hilar and thoracic duct lymph in the dog.
A simultaneous morphological and quantitative profile was obtained of the cells of blood, thoracic duct, and renal hilar lymph in the dog. Monolayer cytocentrifuged preparations were used to determine the number, type, and size of cells in the three compartments. The cell count of renal lymph was not related to that of blood or thoracic duct lymph. There was a greater percentage of lymphoid cells in the afferent lymph than could be accounted for by the random movement of cells from the blood to the lymph. Thus, there appeared to be a selective transit of cells from blood to lymph. Monocytes and neutrophils were largely absent from the thoracic duct lymph; however, eosinophils were present. Cells were observed in hilar lymph that were characteristic of cells subjected to antigenic stimulation. It was concluded that lymphocytes have a preferential pathway from blood to lymphatic and in the course of this pathway they undergo a change which is consistent with an active immunological role.
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.