Search PubMed⌕ Search

Biomedical subjects

C Armstrong

Publications and source records attributed to C Armstrong.

At least 19 recordsLinked to original sources
PubMed1996

Fumonisin B1 toxicity in male Sprague-Dawley rats.

Male rats were gavaged with fumonisin B1 (FB1) once daily for 11 consecutive days at doses of 0, 1, 5, 15, 35, and 75 mg FB1/kg body weight. Urine osmolality (at 5-75 mg FB1/kg) and organic ion transport in kidney slices (at 5-75 mg FB1/kg) were reduced. Urinary excretion of protein (at 15-75 mg FB1/kg) and of the enzymes LDH (at 5-75 mg FB1/kg), NAG (at 5-75 mg FB1/kg) and GGT (at 15-75 mg FB1/kg) were increased. These findings were indicative of glomerular and tubular toxicity. Histopathologic changes in the kidney consisted of necrosis of tubular epithelia of variable extent accentuated in the inner cortex. These changes were present at 1 and 5 mg FB1/kg and were more pronounced at 15-75 mg FB1/kg. Serum enzymes indicative of hepatotoxicity (ALT, GGT) were elevated compared to controls at 75 mg FB1/kg only. There were noticeable increases in mitotic figures in hepatocytes at 35-75 mg FB1/kg, while single cell necroses were increasingly numerous from 15-75 mg FB1/kg. The kidneys were considered to be the primary target organs in this study.

Acetylglucosaminidase↗
PubMed1996

Serial position and temporal cue effects in multiple sclerosis: two subtypes of defective memory mechanisms.

Neurocognitive studies of multiple sclerosis (MS) have identified a robust long-term memory deficit. We hypothesized that this is due in part to the limited representation and use of serial order information. MS patients and controls were studied with a supraspan list learning procedure with post-encoding retrieval and recognition trials. MS patients demonstrated post-encoding negative recency with normal recognition, and word order recall was impaired. These findings appear to be in part to difficulty using temporal order cues in long-term memory. Two dissociable memory deficits were identified, suggesting that there are at least two neurocognitive mechanisms underlying memory impairment in MS.

Adult↗
PubMed1996

The effects of propofol on hemodynamics and renal blood flow in healthy and in septic sheep, and combined with fentanyl in septic sheep.

Sepsis is characterized by myocardial depression and systemic vasodilation, both of which are most likely mediated by nitric oxide. Propofol inhibits nitric oxide synthase and may therefore be beneficial in sepsis. On the other hand, renal blood flow, known to be only minimally affected by propofol in healthy subjects, may be drastically reduced in septic individuals, because the renal microvasculature is known to be very sensitive to nitric oxide. In this study, the effects of propofol in healthy and in septic sheep, and in combination with fentanyl, were analyzed and compared with nonanesthetized septic sheep. In healthy sheep, propofol caused only minor hemodynamic changes. In septic sheep, however, hemodynamics deteriorated. Renal blood flow was reduced to 60% +/- 10% of the preseptic baseline and to 39% +/- 4% of the septic value. This reduction was selective, since the cardiac output decreased significantly less. These adverse effects of propofol on hemodynamics and renal blood flow were reduced when propofol was combined with fentanyl.

Adjuvants, Anesthesia↗
PubMed1995

Calcium signaling in a narrow somatic submembrane shell during synaptic activity in cerebellar Purkinje neurons.

Temporal and spatial changes in the intracellular Ca2+ concentration ([Ca2+]i) were examined in dendrites and somata of rat cerebellar Purkinje neurons by combining whole-cell patch-clamp recording and fast confocal laser-scanning microscopy. In cells loaded via the patch pipette with the high-affinity Ca2+ indicator Calcium Green-1 (Kd approximately 220 nM), a single synaptic climbing fiber response, a so-called complex spike, resulted in a transient elevation of [Ca2+]i that showed distinct differences among various subcellular compartments. With conventional imaging, the Ca2+ signals were prominent in the dendrites and almost absent in the soma. Confocal recordings from the somatic region, however, revealed steep transient increases in [Ca2+]i that were confined to a submembrane shell of 2- to 3-microns thickness. In the central parts of the soma [Ca2+]i increases were much slower and had smaller amplitudes. The kinetics and amplitudes of the changes in [Ca2+]i were analyzed in more detail by using the fast, low-affinity Ca2+ indicator Calcium Green-5N (Kd approximately 17 microM). We found that brief depolarizing pulses produced [Ca2+]i increases in a narrow somatic submembrane shell that resembled those seen in the dendrites. These results provide direct experimental evidence that the surface-to-volume ratio is a critical determinant of the spatiotemporal pattern of Ca2+ signals evoked by synaptic activity in neurons.

Animals↗
PubMed1995

Toxicity of fumonisin B1 administered intraperitoneally to male Sprague-Dawley rats.

The toxicity of purified fumonisin B1 (FB1) administered ip was examined in male Sprague-Dawley rats. FB1 was injected at 7.5 or 10 mg/kg body weight/day for 4 consecutive days. This resulted in significant reductions in body weight, food consumption and faeces production. Polyuria without a compensatory increase in water consumption was observed in treated rats. Erythrocytosis, elevated haematocrits and haemoglobin levels were attributed to dehydration. Nephrotoxicity in treated rats was evident by clinical changes including elevated blood urea nitrogen and by subtle changes in kidney morphology. Histopathology and serum biochemistry also indicated that the liver was an important target organ in FB1-treated rats. A small increase in liver glutathione concentration was also evident in rats receiving 10 mg FB1/kg body weight. Effects on the immune system included reduced thymus weight, disseminated thymic necrosis and consistently elevated serum immunoglobulin M levels. Circulating phagocytic cell numbers were elevated in treated rats, probably owning to tissue damage associated with ip dosing. The liver and kidneys appear to be target organs of FB1 in Sprague-Dawley rats.

Animals↗
PubMed1995

Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms.

PURPOSE: To identify the longitudinal neurobehavioral characteristics of the early-delayed and late-delayed effects of partial-brain radiotherapy for patients with supratentorial brain tumors with favorable histology. This study improves on previous attempts to identify radiation effects, because of the inclusion of baseline measures and the use of subjects as their own controls. PATIENTS AND METHODS: Ten neuropsychologic domains were measured in 12 patients at baseline (post-surgery and immediately before initiation of radiotherapy), and followed trimonthly for 1 year. Four to six patients were examined at 2 and 3 years postbaseline. RESULTS: Patients were impaired at baseline compared with controls only in visual memory and sentence recall, but demonstrated significant improvement in visual memory by 2 years postbaseline. Speed of processing information also showed a slope of improvement over 2 years. Retrieval from verbal long-term memory was impaired at 1.5 months postcompletion of radiotherapy, but recovered to baseline levels by 1 year. At 2 years postbaseline, long-term memory retrieval demonstrated a decline, but remained unchanged at 3 years. CONCLUSION: Long-term memory appears to be sensitive to the effects of radiotherapy. We confirmed our previous findings of a decrement with rebound during the early-delayed period, and propose that these findings are consistent with demyelination/remyelination. Decrement was observed again at 2 years postbaseline, which suggests that memory retrieval may be the earliest marker of late-delayed effects. These neurocognitive patterns are consistent with leukoencephalopathy. Confirmation of these observations will be possible if neuropsychologic testing with the same sensitivity can be incorporated into national collaborative trials.

Adult↗
PubMed1993

Synaptically triggered action potentials in dendrites.

We tested the hypothesis that action potentials originate in apical dendrites of pyramidal cells. Layer V somata were voltage clamped in thin slices of rat motor cortex. Fibers synapsing in unclamped regions far out on the apical dendrite caused small, slow synaptic currents, as recorded at the soma, and sometimes elicited complex, multicomponent current spikes, beginning with a small first spike. Hyperpolarization, or tetrodotoxin applied to basal dendrites and soma, blocked the later spike components without affecting the synaptic current and the first component, which was a synaptically triggered Na+ spike in the apical dendrite. Similar spikes followed voltage steps or direct stimulation. We conclude that Na+ action potentials are initiated in the apical dendrite in response to synaptic input.

Action Potentials↗
PubMed1993

Follow-up of a cohort of men with untreated benign prostatic hyperplasia.

A cohort of 266 men with untreated benign prostatic hyperplasia (BPH) identified in a community-based survey were followed for a period of 1 year. Although the overall prevalence of urinary symptoms increased during the year, substantial within-subject variation in urinary symptomatology occurred, with up to a quarter of men reporting urgency and dribbling to have improved whilst one third of men reported other urinary symptoms to have deteriorated. Levels of bothersomeness caused by urinary symptoms did not show much change during the period of follow-up. An overall increase of 19% in urinary peak flow which was also consistent across all age groups was present at 1 year compared with baseline, even after adjusting for increased urinary void volume. A slow progression in the extent to which interference with selected activities of daily living by urinary dysfunction occurred. This was greater in men of working age (40-64 years), compared with men of retirement age (65-79 years). A longer period of observation is required in order to determine the extent to which a consistent pattern of urinary symptomatology exists in untreated BPH, as well as whether interference with daily living activities continues to progress over time.

Activities of Daily Living↗
PubMed1993

Effects of radiation therapy on adult brain behavior: evidence for a rebound phenomenon in a phase 1 trial.

Although radiotherapy (XRT) is a necessary course of treatment to prolong life expectancy in patients with many types of brain neoplasms, it has damaging effects that are little understood. We used a comprehensive neuropsychological battery to evaluate five patients with low-grade brain tumors prior to XRT and then at 3-month intervals up to 9 months postcompletion of XRT. We matched patients by age and education with six normal control subjects to assess baseline impairment. In intrasubject comparisons, we examined change over time postcompletion of XRT. In spite of varying locations of tumors, all patients showed deterioration in long-term memory at a mean of 1.5 months postcompletion of XRT. Patients also consistently demonstrated a rebound effect between means of 4.7 and 7.6 months post-XRT. We found no changes over time in working memory, attention, visuospatial processes, or on any other neuropsychological test with the exception of information-processing speed, which quickened over time. Functional measures of fatigue and mood did not correlate significantly with the long-term memory scores. Long-term memory appears sensitive to the proposed white matter changes thought to be the mechanism for the early-delayed effects of XRT. Our findings suggest a neurobehavioral model for studying the effects of XRT on brain functioning.

Adult↗
PubMed1993

Ground reaction forces in high impact and low impact aerobic dance.

The purpose of this study was to compare ground reaction forces (vertical and lateral) produced during commonly used high and low impact aerobic dance maneuvers. Eight experienced aerobic dance instructors were the volunteer subjects. During the first session, three subjects were videotaped performing 10 high and 10 low impact maneuvers that they commonly used in their own class routines. Seven of the high and nine of the low impact maneuvers were then selected and used in sessions 2 and 3. During the second session, all subjects became proficient in performing the chosen maneuvers to music while striking an AMTI force platform with the right foot. During the third session, ground reaction force data generated during footstrike were recorded for each movement. Of the maneuvers examined, 5 high and four low impact maneuvers were used in the data analysis. It was found that maximum vertical active peak and vertical impact peak forces were lower for the low impact maneuvers. Maximum lateral active peak and lateral impact peak forces were similar and highly variable in magnitude for the 2 types of dance. The lower vertical loads produced in low impact dancing may make this type of dance better for minimizing lower extremity overuse injuries in aerobic dance. However, there does not seem to be any advantage in emphasizing the use of low impact dance for minimizing lower extremity injuries that evolve from lateral shear forces.

Adult↗
PubMed1993

HLA polymorphism in the Havasupai: evidence for balancing selection.

The characterization and analysis of genetic variation at the HLA loci provides important insight for population geneticists trying to understand the evolutionary forces that have shaped human populations. This study describes the HLA-A and HLA-B loci serotyping and statistical analysis on an isolated Native American population, the Havasupai of Arizona. Four alleles at the HLA-A locus were identified, while eight alleles were found at the HLA-B locus. These variants were present as 20 of 32 potential two-locus haplotypes, with five of the six most common haplotypes exhibiting high positive linkage disequilibrium. Significant homozygote deficiency (heterozygosity excess) was detected both at HLA-A and at HLA-B. This deviation from Hardy-Weinberg proportions was not attributable to nonselective causes such as different allele frequencies in males and females or avoidance of consanguineous matings. In addition, the distribution of alleles at both HLA-A and HLA-B was more even than expected from neutrality theory; that is, the observed Hardy-Weinberg homozygosity was only 62.4% of that expected under neutrality. These observations suggest that balancing selection is of major importance in maintaining genetic variation at HLA-A and HLA-B.

Female↗
PubMed1992

Affected paroxysmal nocturnal hemoglobinuria T lymphocytes harbor a common defect in assembly of N-acetyl-D-glucosamine inositol phospholipid corresponding to that in class A Thy-1- murine lymphoma mutants.

Deficient expression of glycoinositol phospholipid (GPI) anchored proteins in affected paroxysmal nocturnal hemoglobinuria (PNH) cells has been traced to a defect in GPI anchor assembly. In a previous study (Schubert, J., Schmidt, R. E., and Medof, M. E. (1993) J. Biol. Chem., in press) we characterized the biosynthesis of putative Man-containing GPI anchor precursors in normal peripheral blood lymphocytes and investigated assembly of these intracellular GPI intermediates in CD48- affected and CD48+ unaffected T and natural killer cell lines of PNH patients. We found that affected T cells from five patients exhibited a uniform defect in which dolichol-phosphoryl-Man was synthesized but no GPI mannolipids were expressed. In this study, membranes of patients' affected T cells were labeled with UDP-[3H]GlcNAc to evaluate earlier steps in GPI synthesis, and intact cells were fused to Thy-1- murine lymphoma mutants harboring different defects in early GPI assembly to test for the presence of corresponding or complementary lesions. In all cases, affected cell membranes failed to assemble GlcNAc-inositol phospholipid, the initial precursor of GPI anchor structures, and the intact cells failed to complement class A mutants while complementing other classes. Affected polymorphonuclear leukocytes from three additional patients of different origin were then labeled with [3H]Man and the labeling patterns found to correspond to those obtained with the T lymphocytes. Taken together the data indicate that the genetic lesion in PNH cells resides in a DNA element which: 1) encodes a product required for the synthesis of GlcNAc-inositol phospholipid, 2) corresponds to that altered in class A Thy-1- murine lymphoma mutants, and 3) is commonly affected in different patients.

Acetylglucosamine↗
PubMed1992

Use of provincial health insurance plan billing data to estimate carpal tunnel syndrome morbidity and surgery rates.

Following a work refusal at a plant manufacturing ice cream novelties in Ontario, we were asked to document cases of cumulative trauma disorders (CTDs) and carpal tunnel syndrome (CTS) in this workplace. There were 17 employees with possible hand and wrist problems identified from Workers Compensation Board (WCB) Forms, and from a list prepared at the time of the refusal. After obtaining consents, confirmations of the diagnoses of CTDs, CTS, and of surgical procedures for CTS were obtained from the physicians involved. The relative risk for these disorders among plant employees was estimated in two ways: 1) the rate of CTS operations between 1979 and 1990 was compared to that in the general population using Ontario Health Insurance Plan (OHIP) data on physicians' billings for these operations; and 2) the frequency of WCB first payment claims for tendinitis and CTS during 1987 to 1989 at the plant was compared to that among the entire labor force of Ontario. CTDs had been diagnosed in all 17 workers: 9 had had operations for CTS, but one had had this operation prior to working at the plant. Compared to the remaining 8 workers who had CTS operations, an estimated 0.08 CTS operations would be expected among the 150 employees on the plant's seniority lists between 1979 and 1990, if the estimated rates in the general population were present at the plant, giving a Standardized Morbidity Ratio of 10.0 (95% confidence interval [CI] 4.3-19.7; one-sided p = 2.1 x 10(-6)). There were 6 WCB claims for tendinitis and CTS among plant employees during 1987 through 1989. This frequency was about 68 times that in the entire Ontario labor force (95% CI 24.7-150). This investigation has shown that CTDs, and particularly CTS, documented by medical records, have occurred at least 10 times more frequently than expected at this plant. Use of health insurance billing data to estimate CTS operation rates represents a simple method for estimating the burden of illness at the individual plant level due to CTS (at least for that portion proceeding to surgery), using an objective outcome that can be confirmed from medical records.

Adult↗
PubMed1992

Interleukin-6 and renal cell cancer: production, regulation, and growth effects.

Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05). The combination of interferon gamma IFN gamma and TNF alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF alpha alone (P less than 0.05). TNF alpha also significantly stimulated the production of biologically active IL-6 (P less than 0.01). Furthermore, IFN gamma and TNF alpha were found to enhance IL-6 bioactivity synergistically (P less than 0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF alpha with synergistic effects seen with IFN gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.

Blotting, Northern↗
PubMed1992

Clinical audit in intensive care--the Meath Intensive Care Audit.

Audit is now recognised as being an essential component of clinical practice. We report on the first year of the Meath Intensive Care Audit (MICA). This audit was instituted to investigate the activity of the unit, to assess the feasibility of continuous audit in our ICU and to provide data for future development of ICU facilities. Two hundred and fifty four patients were admitted between July 1st 1990 and June 30th 1991. The mean age at admission was 58 years and the mean length of stay 5.2 days. The mean APACHE II score was 16. Thirty four patients (13.4%) died in the ICU and 17 patients died in hospital following discharge from the unit bringing the hospital mortality rate to 20%. The audit proved feasible to implement and data collection is now accepted as a routine part of our ICU work.

Cause of Death↗