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Biomedical subjects

D W Coombs

Publications and source records attributed to D W Coombs.

At least 37 records · Page 2Linked to original sources
PubMed1993

Neurotoxicology of chronic infusion of the ganglioside GM1 in the ewe: phase I. intrathecal administration.

Gangliosides, including GM1, provide a measure of improved functional recovery after ischemic, toxic, and traumatic brain injuries in animal studies. Since systemically injected GM1 has provided equivocal results in a variety of human neurodegenerative conditions, the possibility exists that intrathecal or intracerebroventricular delivery might provide more effective concentrations along the neuroaxis. In preparation to consider clinical trials, the potential neurotoxicologic effects of chronic intrathecal GM1 were studied in ewes. Preliminary in vitro tests first demonstrated the stability and compatibility of GM1 in implanted pumps. Two groups of adult ewes were then implanted with either Therex or Infusaid continuous flow implantable pumps and chronic intrathecal catheters. Ewes were infused intrathecally with either preservative-free normal saline (n = 5) or GM1 (n = 7) 100 micrograms-10,000 micrograms/d for up to 24 wk. No abnormal behavioral responses were noted. Cerebrospinal fluid analyzed for GM1 concentrations by thin layer chromatography revealed no evidence of GM1 accumulation. After the animals were killed, spinal cords were removed, fixed, sectioned, and stained. Histologic analysis revealed no generalized pattern of neuronal damage, demyelination, gliosis, or axonopathy to distinguish intrathecal normal saline or GM1. In both treated and control groups, the only consistent finding was a pericatheter-associated compression of white matter with axonal dilation, vacuolation, and occasional neuronal loss. Catheter tracts in both groups were also associated with variable leptomeningeal fibroproliferative changes in adjacent dura and pia, at times in conjunction with more generalized duromeningeal thickening. In summary, chronic intrathecal GM1 in doses up to 10 mg/d had no definable neuropathologic consequences.

Animals↗
PubMed1992

Analgesic effects of intrathecally-administered 3 alpha-hydroxy-5 alpha-pregnan-20-one in a rat mechanical visceral pain model.

Recent studies in animals have demonstrated that the steroid, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3A5P), is a potent analgesic when given intracerebroventricularly. Several studies in humans report that spinal steroids are effective in the treatment of chronic low-back pain when given in combination with morphine. The spinal antinociceptive effect of steroids, in particular a progesterone metabolite has not been studied in a visceral pain model. The experiments in the following study were designed to test, first, if the intrathecally-administered (i.t.) steroid, 3A5P, has analgesic properties in a mechanical visceral nociceptive assay, and second, if the intrathecal coadministration of this steroid and morphine is more effective than either therapy alone. Our mechanical visceral pain model (VPM) consists of a chronic indwelling duodenal balloon catheter implanted in the rat. The balloon is inflated to elicit a writhing response. Protection values are defined as the percentage of rats in each group which did not writhe. In this model, 3A5P was found to provide a dose-independent, though significant (p less than 0.01), antinociception when administered alone (33-67% protection vs. 0-25% for controls). Yet, protection offered by the coadministration of 3A5P and morphine (79%) was not significantly greater than that offered by morphine alone (85%). Unlike a dose and time-dependent response observed in a thermal cutaneous nociceptive assay, the antinociception of 3A5P was not dose-dependent when challenged with a mechanical visceral noxious stimulus.

Analgesics↗
PubMed1992

A survey of complications documented in a quality-control analysis of patient-controlled analgesia in the postoperative patient.

Patient-controlled analgesia (PCA) has become a cornerstone of postoperative pain management in many institutions. Despite the extensive use of this analgesic technique, there are not large population studies to determine the frequency or types of complications associated with PCA in the literature. This study looks at 1122 patients over a 1-yr period. Eight significant complications associated with PCA use were noted during this period. These complications were attributable to overdosage (escalating dosage to meet patient analgesic needs or someone other than the patient administering drug through the PCA device) or to interaction of PCA drugs with concurrent medications. There was a much higher incidence of complications associated with PCA pumps featuring continuous infusion in addition to intermittent bolus compared with those employing intermittent bolus alone. The types of complications encountered in this survey demonstrate instances of PCA use that may present a higher risk to the patient and thus require closer monitoring.

Adult↗
PubMed1992

Continuous infusion of intrathecal morphine to control acquired immunodeficiency syndrome-associated bladder pain.

A 36-year-old man with acquired immunodeficiency syndrome had incapacitating dysuria and vesical pain secondary to interstitial cystitis. When medical management and suprapubic urinary diversion failed to control the symptoms the patient was started on subarachnoid morphine sulfate. Bupivacaine was added 1 year later via an implanted Therex M-3000 implantable continuous infusion pump, which has continued successfully for more than 18 months. We believe that subarachnoid narcotics and other analgesic agents, such as clonidine, bupivacaine hydrochloride and baclofen, may prove equally valuable in the treatment of bladder spasm and pain. Furthermore, implanted intrathecal ports and pumps may have less associated risk of infection than the percutaneous vascular access catheters presently used for the continuous delivery of medications in immunosuppressed patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

An application of the LePSA methodology for health education in leprosy.

This paper describes how the innovative LePSA technique can be used by community health workers to appropriately educate and increase compliance among leprosy patients. A lesson plan illustrating the interactive nature of the technique in a hypothetical Third World community is presented. The lesson plan, using MDT default, shows how the technique can elicit individual participation in a group setting and serve as both an educational and a behaviour change tool.

Humans↗
PubMed1992

Presuicide attempt communications between parasuicides and consulted caregivers.

A high percentage of parasuicides visit professional caregivers prior to the attempted suicide. The content or outcome of these consultations is unknown. We interviewed hospitalized attempters and the professional caregivers they identified as having been consulted prior to their attempts. About half of these patients directly disclosed suicidal symptoms or intentions, especially to mental health professionals. These professionals more often inquired about suicidal ideations than did nonpsychiatric physicians. However, few caregivers noted suicidal thinking or probed suicidal symptoms. The data suggest that professional caregivers and especially nonpsychiatric physicians should be more sensitive and responsive to the signs and symptoms of suicidality.

Adolescent↗
PubMed1991

Autotomy and decreased spinal substance P following peripheral cryogenic nerve lesion.

Cryotherapy has been clinically applied to relieve pain by blocking peripheral nerve function. Clinically, analgesia has been successfully achieved but there is suggestion that permanent pain relief may be accompanied by extended motor and sensory deficits. This study was undertaken to determine the effect of a peripheral cryogenic nerve lesion, i.e., of the sciatic nerve, on behavioral effects and substance P content in the dorsal horn of the spinal cord. In rats, the right sciatic nerve was exposed and cryolesioned using one freeze-thaw-refreeze cycle. In an alternate group, the right sciatic nerve was cut and a 3-mm region was excised. Animals were allowed to recover 7 or 21 days during which their behavior was assessed. Autotomy, an animal's tendency to attack the nerve-injured affected limb, occurred in both the cryolesioned and sectioned groups. They were killed by transcardiac perfusion of fixative and segments L4-S1 were processed for immunocytochemistry. The SP-like immunoreactivity (SPLI) in the right and left dorsal horns was compared and quantitated using a microcomputer imaging device. We utilized a fully automated program to digitize and quantitate the staining of the substantia gelatinosa. There was no significant difference in SPLI in the dorsal horns of the sham-operated controls at either time period. At 7 days the sectioned group demonstrated a 40% decrease in SPLI and 76% decrease at 21 days. In the cryolesioned group, there was a 34% decrease at 7 days and by 21 days there was a 68% decrease in immunoreactivity on the operated side.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Differential c-fos-like protein expression in mechanically versus chemically induced visceral nociception.

The expression of c-fos-like protein has been suggested to be a marker for neuronal activity in nociceptive processing. The immunohistochemical detection of this protein was used to determine if different visceral noxious stimuli induce distinct patterns in the rat spinal cord. We have developed a mechanical visceral pain model which is based on the acute distention of the duodenum yielding a quantifiable behavioral endpoint, writhing-like activity. One hour following either intraperitoneal injection of acetic acid or the distention of the duodenum via a chronically implanted balloon catheter, the animals were processed for the immunocytochemical detection of c-fos-like protein in the spinal cord. Characteristic patterns of c-fos-like immunoreactivity were observed following each type of stimulus that differed in spinal laminar and segmental distribution, number of neurons expressing fos-like immunoreactivity and staining intensity. The chemical noxious stimulus induced c-fos bilaterally in laminae I and X predominantly in the thoraco-lumbar region of the spinal cord. In contrast, the mechanical noxious stimulus induced a greater number and more intense neuronal c-fos-like protein expression in laminae I-VI, IX and X. These data provide further evidence that there is a differential nociceptive modulation in mechanical noxious visceral stimulation.

Animals↗
PubMed1989

Mechanical visceral pain model: chronic intermittent intestinal distention in the rat.

Animal models designed to test the effectiveness of analgesic agents against viceral pain typically rely on a noxious chemical irritation of the peritoneum, e.g., acetic acid and phenylquinone writhing tests. While useful, this type of assay depends upon an acute inflammation and the release of local alogens. Further, ethical and scientific constraints prevent repeated assessments in a single animal, thereby compounding the difficulty of assessing tolerance development to analgesic agents. To overcome these constraints we developed a model for mechanical visceral pain (VPM) based on a repeatable and reversible duodenal distention in the rat. A chronic indwelling intraduodenal balloon catheter is well tolerated and upon inflation produces a writhing response graded in proportion to distention. This response is inhibited by morphine in a dose dependent manner.

Animals↗
PubMed1989

The differentiation of NSAIDs and prostaglandin action using a mechanical visceral pain model in the rat.

In order to determine the role of peripheral prostanoids in a newly developed mechanical visceral pain model, several NSAIDs were studied. Systemic acetylsalicylic acid and mefenamic acid, in doses known to produce cyclooxygenase inhibition, produced limited or no analgesia using a duodenal distension model and a behavioral scale for assessment. In contrast, indomethacin at 1 mg/kg, a dose 1/100th of the highest dose of the above compounds, had a marked analgesic effect in the visceral pain model (32% of control response). These data suggest that a duodenal distension stimulus does not have a peripheral prostaglandin E2-mediated nociceptive mechanism. Furthermore, the results obtained with indomethacin support an alternate, possibly central nonprostanoid visceral antinociceptive action.

Acetates↗
PubMed1989

Selection of implantable narcotic delivery systems.

Intraspinal narcotics have dramatically influenced the way pain of malignant origin is managed. There has been a rapid acceptance of this modality within the anesthesia community to treat a wide variety of cancer pain problems. In tandem the development of various implantable narcotic delivery systems has complemented and facilitated the expanded role of intraspinal narcotics in the treatment of cancer pain. Appropriate patient selection is crucial if optimal results are to be achieved. Factors to be considered in patient selection should include the results of the preimplantation spinal narcotic trial, infection trial, infection and local conditions, hematologic status, physiologic and behavioral abnormalities, cost, patient support systems and life expectancy. By interfacing these factors with the unique profiles that each of the five types of implantable narcotic delivery systems offer, improved results both in terms of pain relief and patient satisfaction can be expected.

Catheters, Indwelling↗
PubMed1987

The chances of false negative results in conventional toxicology studies with rats.

Data from conventional rat toxicology studies from 2 centres are used to estimate the coefficients of variation of organ weights, haematology and blood chemistry characteristics commonly measured in such studies. Charts, based on simple statistical formulae, are provided which enable this information to be used to indicate the probability of failing to detect a treatment effect of a given magnitude as statistically significant. The results, for a study with 20 rats/treatment group, when the treatment causes a change of 10% in the characteristic, indicate wide variability in the false negative error rate. With some characteristics (e.g. haemoglobin, total protein, brain weight, red blood cell count) the false negative rate is less than 0.1%, but for others (e.g. white blood cell count, glutamic-pyruvic transaminase, pituitary weight, cholesterol) it is in excess of 70%.

Animals↗
PubMed1987

Comparison of hypertension prevalence and control in 5,237 rural and urban Alabama residents.

Selected urban and rural Alabama populations were compared by age, sex, and race on the prevalence of hypertension and uncontrolled hypertension and the percentage of treated hypertensives with controlled blood pressure. We found the following results: (1) Rural women had a significantly higher prevalence of hypertension than urban women. (2) The prevalence of uncontrolled hypertension was significantly higher for urban white men than for their rural counterparts. (3) The prevalence of uncontrolled hypertension was significantly higher for rural black women aged 30 to 39 than for the same age group of urban black women. (4) Rural dwellers generally had much better blood pressure control than urban, though this was not manifested evenly across groups. Statistically significant differences were found for white men and women of all ages combined and in three of four age groups. Reasons for the rural-urban differences are unclear, but the rural area surveyed was served by nurse practitioner clinics that strongly emphasized patient education.

Adult↗