Biomedical subjects

C A Wallace

Publications and source records attributed to C A Wallace.

54 records · Page 3Linked to original sources

PubMed1989

Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis.

Twenty-three children with destructive polyarticular juvenile rheumatoid arthritis (JRA) were treated for 0.5-4.3 years (median 1.6 years) with weekly doses of methotrexate (MTX) (0.11-0.6 mg/kg/week). Serum levels of MTX at 1 hour and at 24 hours after drug administration were obtained at each dosage level and every 3 months after a stable dosage was achieved. No patient had serum levels of MTX that were in the toxic range nor evidence of hematologic, skin, mucous membrane, gastrointestinal, or pulmonary abnormalities. Ten patients had transiently elevated serum transaminase levels. Arthritis symptoms improved in 21 of these JRA patients, and the improvement was significantly associated with a mean 1-hour serum MTX level of greater than or equal to 5.8 x 10(-7)M (P = 0.008) and a dosage of greater than or equal to 0.3 mg/kg/week (P = 0.004). The 1-hour serum level of MTX was correlated with the MTX dosage (r = 0.28, P = 0.005). Our observations suggest that with close monitoring, MTX can be used safely at dosages as high as 0.6 mg/kg/week, and improvement in the symptoms of JRA will become evident when the serum levels of MTX 1 hour after administration approach 6.0 x 10(-7)M.

Administration, Oral↗

PubMed1989

Dopaminergic agents differentially regulate both processing and content of alpha-N-acetylated endorphin and alpha-MSH in the ovine pituitary intermediate lobe.

Hypothalamo-pituitary disconnection (HPD) in the sheep results in a two-fold increase in pituitary intermediate lobe (IL) immunoreactive (ir)-alpha-N-acetylated endorphin (NacEP) and ir-alpha-melanocyte-stimulating hormone (alpha MSH) content. The rise in IL NacEP content is accompanied by a markedly altered pattern of processing, in that NacEP1-27 becomes the dominant molecular species with a complementary fall in Nac alpha-EP and Nac gamma-EP. To determine if these effects reflect the loss of descending dopaminergic neuronal input to the IL, we have chronically treated two groups (n = 4 per group) of normal sheep with the dopamine antagonist haloperidol or the dopamine agonist bromocriptine; a group of HPD sheep were also treated with bromocriptine. Acid extracts of IL were diluted and ir-alpha-MSH and ir-NacEP content determined by radioimmunoassay; aliquots were submitted to reversed-phase HPLC and collected fractions similarly assayed. Bromocriptine lowered ir-NacEP and ir-alpha-MSH by about 30%; on HPLC the ir-NacEP profiles, and perhaps to a lesser extent those for ir-alpha-MSH were qualitatively similar to untreated controls. In contrast, haloperidol increased by about 45% both ir-NacEP and ir-alpha-MSH levels and produced a marked change in the ir-NacEP molecular profile, with NacEP1-27 becoming the predominant molecular form and other species representing only minor components in the chromatogram. In the treated HPD group, bromocriptine partially restored the processing profiles previously observed in HPD animals to those found in untreated intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Effect of myiasis and acute restraint stress on plasma levels of immunoreactive beta-endorphin, adrenocorticotrophin (ACTH) and cortisol in the sheep.

Cutaneous myiasis in sheep arising from the activity of Lucilia cuprina larvae can result in significant physiological changes in susceptible animals. The stress imposed on the pituitary-adrenal axis of the sheep in response to myiasis and acute restraint is the subject of this investigation. Merino wethers were exposed to handling restraint, and blood sampling, during examination for blowfly strike; where necessary, they were treated for cutaneous myiasis. Significant changes in the plasma concentrations of immunoreactive beta-endorphin (beta-EP), ACTH and cortisol were found in sheep with extensive myiasis, as compared with unstruck sheep or those with only localized myiasis. In five susceptible sheep with extensive cutaneous myiasis, mean plasma levels of beta-EP, ACTH and cortisol were 307 +/- 71 pg ml-1, 953 +/- 58 pg ml-1 and 232 +/- 46 nmol l-1 respectively, compared with 818 +/- 89 pg ml-1, 641 +/- 41 pg ml-1 and 107 +/- 17 nmol l-1 in six unstruck sheep handled similarly. Whereas significant increases in plasma ACTH and cortisol can result from pituitary-adrenal responses to acute emotional or surgical stress, and are usually accompanied by a concomitant release of beta-EP from the pituitary, the present findings indicate a marked reduction in beta-EP levels and a significant increase in ACTH and cortisol in sheep following blowfly strike and acute handling restraint. This result suggests that cutaneous myiasis in susceptible sheep can alter the pituitary-adrenal response to acute restraint stress, and this could occur either by an alteration of precursor processing in the pituitary or by the selective release of ACTH.

Adrenocorticotropic Hormone↗

PubMed1988

An unusual phosphatidylinositol turnover pathway in noradrenaline-perfused rat hearts.

1. The phosphatidylinositol turnover pathway has been studied in noradrenaline-perfused rat hearts using anion-exchange high performance liquid chromatography. 2. The active calcium-releasing compound inositol-(1,4,5)trisphosphate was detected together with its degradation products inositol-(1,4)bisphosphate and inositol monophosphate. All these products increased in response to noradrenaline stimulation. 3. At noradrenaline perfusion times from 5 s to 20 min there was no appearance of inositol-(1,3,4,5)tetrakisphosphate or its degradation products: inositol-(1,3,4)trisphosphate or inositol-(1,3) and (3,4)bisphosphates. 4. These data suggest the absence of the inositol-(1,4,5)trisphosphate phosphorylation/dephosphorylation pathway in heart.

Angiotensin II↗

PubMed1987

Evidence for a lack of inositol--(1,4,5)trisphosphate kinase activity in norepinephrine-perfused rat hearts.

The products of the phosphatidylinositol turnover pathway in norepinephrine-perfused hearts have been examined using high performance liquid chromatography. Inositol-1 phosphate, inositol-(1,4)bisphosphate and inositol-(1,4,5)-trisphosphate were all increased in response to norepinephrine stimulation. However, at perfusion times from 5 sec to 20 min there was no appearance of inositol-(1,3,4,5)tetrakisphosphate or inositol-(1,3,4)trisphosphate. This suggests the absence of the inositol-(1,4,5)trisphosphate phosphorylation/dephosphorylation pathway in heart and demonstrates that this secondary pathway is not essential to the functioning of the phosphatidylinositol turnover cycle.

Adrenal Glands↗

PubMed1987

The combined use of size-exclusion and reversed-phase high-performance liquid chromatography for characterization of beta-endorphin processing pathways.

A method is described for the separation and analysis of multiple molecular forms of immunoreactive beta-endorphin and its alpha-N-acetylated congeners by a combination of reversed-phase and size-exclusion high-performance liquid chromatography coupled with two specific radioimmunoassays. Both chromatographic procedures are fast (less than 50 min per analysis) providing good resolution and high recovery (greater than 90%). The solvents used in both systems are ultraviolet transparent (less than 214 nm), non-corrosive, low salt (less than 0.05 M) and after evaporation fully compatible with subsequent radioimmunoassay. We have evaluated these techniques using both synthetic and purified peptide standards and have applied these procedures to characterize immunoreactive beta-endorphin and alpha-N-acetylendorphin in rat and sheep pituitary extracts, and the low levels found in sheep hypothalamus and rat ovary. These chromatographic procedures are not only applicable to the study of pro-opiomelanocortin-derived peptides, but also could be employed to examine the processing pathways of other biologically active polypeptides, in both central and peripheral tissue extracts.

Animals↗

PubMed1987

Isolation, amino acid sequence and action of guinea-pig ACTH on aldosterone production by glomerulosa cells.

Though minor sequence differences between-species have been reported for adrenocorticotrophin, ACTH(1-39), the steroidogenic moiety ACTH(1-24) has appeared invariant in mammals. We here report the isolation, purification and amino acid sequencing of guinea-pig (GP) ACTH in which Pro24 is replaced by Ala24, and the demonstration that GP-ACTH stimulates aldosterone production to maximal levels well above those seen with human ACTH(1-39) or Synacthen, ACTH(1-24) amide, the synthetic ACTH fragment widely used for diagnostic and therapeutic purposes.

Adrenal Cortex↗

PubMed1987

Stress-induced changes in plasma concentrations of immunoreactive beta-endorphin and cortisol in response to routine surgical procedures in lambs.

Following four different surgical procedures in lambs 3-5 weeks old, plasma immunoreactive beta-endorphin (beta-EP) and cortisol were assayed at 15 min and 24 h as determinants of post-operative stress. A threefold increase in mean plasma beta-EP levels occurred 15 min after tail docking, and a maximal eight- to tenfold increase occurred in response to castration and/or mulesing with tail docking. Significant increments in mean plasma cortisol levels followed these surgical procedures with the maximal response 15 min after mulesing plus castration with tail docking. The physiologically active 'free' cortisol in plasma represents about 25% of the cortisol, as measured, and the two are highly correlated. At 24 h, beta-EP levels in all treated groups were similar to controls, although a small elevation in cortisol levels was still present in the lambs subjected to mulesing. Ultrafiltration of plasma extracts showed that peak beta-EP levels contained about 40% immunoreactivity from low molecular weight species (mol. wt less than 10,000). By specific radioimmunoassay and reverse-phase high-performance liquid chromatography this comprised about 75% beta-EP1-31, the most potent analgesic endorphin, 10% beta-EP1-27, and 15% alpha-N-acetyl-beta-EP. Increased beta-EP1-31 levels may modulate post-operative pain in lambs.

Animal Welfare↗

PubMed1986

alpha-N-acetylated beta-endorphin is differentially processed in the normal and hypothalamo-pituitary-disconnected (HPD) ewe.

We have used specific radioimmunoassay and high-performance liquid chromatography (HPLC) to determine content and molecular forms of pituitary alpha-N-acetylated endorphin (NacEP) in the intact and hypothalamo-pituitary-disconnected (HPD) sheep. No significant differences were seen in anterior pituitary (AP) immunoreactive (ir-) NacEP levels (control = 4.34 +/- 0.45 ng/mg; HPD = 4.38 +/- 0.83 ng/mg; n = 4) or in HPLC profiles following pituitary disconnection. In contrast, levels of ir-NacEP in the HPD intermediate lobe (IL) (263 +/- 16.5 ng/mg; n = 4) were double those in the control (110 +/- 14 ng/mg; n = 4), accompanied by a marked change in the molecular profile. In the control IL, the major species were Nac alpha EP (30%), Nac gamma EP (30%) and Nac beta EP1-27 (35%); in HPD IL, Nac beta EP1-27 (65%) is the dominant molecular form, with Nac alpha EP (11%) and Nac gamma EP (9%) relatively minor components.

Animals↗

PubMed1983

Recovery from spinal cord injury.

There are many classifications of spinal cord injury. The anatomic definitions help in understanding the pathophysiology but are less useful in calculating recovery. Basic classifications, such as those by Guttman and Frankel, are useful for epidemiological studies, especially if one wishes to compare patients internationally or to compare data bases but this information, except in complete lesions, is too limited to allow more refined calculations as to the effectiveness of treatment modalities, especially in partial lesions. An accurate motor index, such as we have described, or such as the Yale index (2), is needed for more specific calculations of recovery if any prediction about the efficacy of various treatments are to be made. We have described our data from the mid-1970s in detail to explain our current treatment protocols. While nothing can be done for the completely paralyzed patient, our treatment of the acute (transiently concussed) near complete lesion and partial lesion must be tailored to maximize recovery. The fact that patients with initially complete motor lesion show some motor recovery in 15% indicates that some lesions are reversible and that we should try to learn to identify these patients and treat them to maximize their recovery. Certain severe partial lesions show poor recovery; we must improve therapy for these patients. Patients with partial lesions and 25-30% motor power below the injury have an 80% (+/- 20%) recovery; we should strive to attain and improve on these good results by appropriate medical and surgical management. In sharing with you our methods and data, we have provided these preliminary conclusions which influence our behavior as neurosurgeons, but it is equally clear that much work still needs to be done. This chapter should represent a reference source with which we can continue to work.

Humans↗

PubMed1978