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Biomedical subjects

M Mayes

Publications and source records attributed to M Mayes.

32 records · Page 2Linked to original sources
PubMed1995

The direct embryotoxicity of immunoglobulin G fractions from patients with systemic lupus erythematosus.

PROBLEM: To determine if IgG fractions from sera of individuals with systemic lupus erythematosus (SLE) were toxic to cultures of whole rat embryos. METHODS: Head-fold stage rat embryos (9.5 days of gestation) were cultured on media consisting of 50% rat serum containing IgG fractions isolated from plasmapheresis plasma of six subjects with SLE and six with other autoimmune diseases. Each fraction was tested at 11 mg/ml and those toxic were also tested at 7.5 and 4 mg/ml. RESULTS: Of the six SLE IgG fractions, four were embryotoxic (embryolethal or teratogenic) while only one of the six non-SLE fractions were embryotoxic. CONCLUSION: IgG fractions from subjects with SLE can be toxic to cultures of whole rat embryos in the absence of maternal tissues or influence. Such cultures of whole embryos may be useful to identify those antibodies that represent a risk for fetal loss as well as to understand their mechanisms of embryotoxicity.

Abortion, Spontaneous↗
PubMed1995

Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis.

OBJECTIVE: Assessment of the inter and intraobserver variability of the modified Rodnan (m-Rodnan) total skin thickness score by clinical palpation [a commonly used outcome measure in trials of systemic sclerosis (SSc)]. METHODS: Skin thickness was assessed by clinical palpation of 17 body areas on 0 to 3 scale (normal, mild, moderate, severe). The m-Rodnan total skin thickness score was derived by summation of the scores from all 17 body areas. Using the m-Rodnan, 6-7 investigators assessed skin thickness in 5-6 patients with SSc (22 patients and 23 examiners total) at each of 4 sessions for the determination of interobserver variability (accuracy). In addition 21 of the investigators then assessed m-Rodnan in 2-3 patients each (60 patients total) 3 times over a 2-8 week period to quantitate intraobserver variability (reliability). RESULTS: Interobserver and intraobserver mean +/- within patient standard deviations (SD) for the m-Rodnan were found to be 17.7 +/- 4.6 and 20.7 +/- 2.45, respectively. CONCLUSION: The m-Rodnan total skin thickness score is at least as reliable for measuring skin thickness in SSc as are the ARA and Ritchie joint tenderness counts for assessing joint disease in rheumatoid arthritis. These data are useful for the determination of sample size and for the definitions of clinically meaningful response. Assessment of skin score is sufficiently reproducible to include as a measure of disease outcome, especially if patients are serially evaluated by the same investigator.

Humans↗
PubMed1994

Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis. DESIGN: Multicenter, randomized, parallel placebo-controlled, double-blind study. SETTING: University medical centers. PATIENTS: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years. INTERVENTION: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo. MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing. RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo. CONCLUSION: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

Adult↗
PubMed1993

Cold-induced potentiation of alpha 2-adrenergic vasoconstriction in primary Raynaud's disease.

OBJECTIVE: To determine the effects of local cooling on alpha-adrenergic responses in the fingers of patients with idiopathic Raynaud's disease. METHODS: Clonidine HCl and phenylephrine HCl were administered through a brachial artery catheter while blood flow was measured by plethysmography in cooled and uncooled fingers. RESULTS: Cooling potentiated alpha 2-adrenergic vasoconstriction in the patients but depressed this response in the controls. Vasoconstrictive responses to phenylephrine were not significantly affected by cooling but were significantly greater in the patients than in the controls. CONCLUSION: Cold-induced sensitization of peripheral vascular alpha 2-adrenoceptors may be involved in the mechanism by which cooling triggers the vasospastic attacks of Raynaud's disease.

Adult↗
PubMed1993

The majority of nitric oxide synthase in pig heart is vascular and not neural.

OBJECTIVE: As a physiological mediator of smooth muscle relaxation and possibly a non-adrenergic non-cholinergic (NANC) neurotransmitter, nitric oxide plays a role in regulating coronary artery blood flow and modulating myocardial contractility. Although recent attention has been directed toward neural tissue, we investigated the possibility that vessels, as well as nerves, may be a source of nitric oxide in the heart. METHODS: The NADPH-diaphorase method was used to localise the synthesis enzyme, nitric oxide synthase (NOS), in the pig heart. RESULTS: All regions showed a similar staining pattern. Muscle fibres had virtually no NOS activity. The endocardium showed reaction product in a lattice configuration without much cytoplasmic staining, suggesting that endothelial cell membranes are the primary site of NOS activity. Every vessel contained reaction product in intima but none in the media or adventitia. Muscular arteries had more NOS activity than veins. Lighter staining capillaries coursed along each muscle fibre. Only a few scattered nerve processes and rare neuronal cell bodies with NOS activity were present in the heart; there was no particular spatial relationship between neural tissue and vessels. CONCLUSIONS: (1) the majority of NOS activity in the pig heart is in vascular endothelium, consistent with the concept of nitric oxide as a regulator of coronary blood flow; less is present in the endocardium; (2) paucity of nerves with NOS activity probably indicates that this particular type of NANC neural tissue does not affect coronary blood flow directly; and (3) although muscle fibres have no discernible NOS activity, the rich vascular supply in close proximity may subserve some myocardial function of nitric oxide.

Amino Acid Oxidoreductases↗
PubMed1991

The spectrum of fiber loss in a model of neuropathic pain in the rat: an electron microscopic study.

Recently, Bennett and Xie reported that when the sciatic nerve of the rat is ligated loosely, the rat develops a pain syndrome with many features similar to those observed in neuropathic pain states in man. Anatomical and physiological studies to date indicate that the major pathology is a loss of large diameter myelinated fibers distal to the ligatures, with more subtle changes in small myelinated fibers. With a view to evaluating possible changes in the unmyelinated fibers, we have performed an electron microscopic analysis of the sciatic nerve 2 weeks after four ligatures were applied, at which time the animals displayed profound hyperalgesia and mechanical and thermal allodynia. Cross-sectional photomontages of regions proximal and distal to the ligatures were studied. Consistent with light microscopic and electrophysiological studies, we found a near complete loss of large myelinated fibers distal to the ligatures. Phagocytosis of large fibers was common. There was also considerable variation in the damage to small myelinated fibers. In some fascicles many small (less than 3 microns) myelinated axons remained; in other fascicles none could be detected. Importantly, we also found significant changes in the unmyelinated fiber spectrum. Counts of unmyelinated axons revealed a 34% and 71% decrease in the distal compared to the proximal nerve, in the two rats studied. The large clusters of unmyelinated axons that characterize normal nerve (and the nerve proximal to the ligatures) were rarely found distally. Rather, many of the unmyelinated axons coursed singly or in very loose bundles. Many of the surviving axons were shrunken and distorted, although still in contact with Schwann cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Expression of syndecan, a putative low affinity fibroblast growth factor receptor, in the early mouse embryo.

Syndecan is an integral membrane proteoglycan that binds cells to several interstitial extracellular matrix components and binds to basic fibroblast-growth factor (bFGF) thus promoting bFGF association with its high-affinity receptor. We find that syndecan expression undergoes striking spatial and temporal changes during the period from the early cleavage through the late gastrula stages in the mouse embryo. Syndecan is detected initially at the 4-cell stage. Between the 4-cell and late morula stages, syndecan is present intracellularly and on the external surfaces of the blastomeres but is absent from regions of cell-cell contact. At the blastocyst stage, syndecan is first detected at cell-cell boundaries throughout the embryo and then, at the time of endoderm segregation, becomes restricted to the first site of matrix accumulation within the embryo, the interface between the primitive ectoderm and primitive endoderm. During gastrulation, syndecan is distributed uniformly on the basolateral cell surfaces of the embryonic ectoderm and definitive embryonic endoderm, but is expressed with an anteroposterior asymmetry on the surface of embryonic mesoderm cells, suggesting that it contributes to the process of mesoderm specification. In the extraembryonic region, syndecan is not detectable on most cells of the central core of the ectoplacental cone, but is strongly expressed by cells undergoing trophoblast giant cell differentiation and remains prominent on differentiated giant cells, suggesting a role in placental development. Immunoprecipitation studies indicate that the size of the syndecan core protein, although larger than that found in adult tissues (75 versus 69 x 10(3) Mr), does not change during peri-implantation development. The size distribution of the intact proteoglycan does change, however, indicating developmental alterations in its glycosaminoglycan composition. These results indicate potential roles for syndecan in epithelial organization of the embryonic ectoderm, in differential axial patterning of the embryonic mesoderm and in trophoblast giant cell function.

Animals↗
PubMed1989

Increased alpha-adrenergic responsiveness in idiopathic Raynaud's disease.

In our study of 28 patients with idiopathic Raynaud's disease, the patients had significantly greater digital blood flow responses to intraarterial phenylephrine and clonidine than did normal control subjects. There were no group differences in finger blood flow responses to body heating, reflex cooling, digital ischemia, or to intraarterial tyramine or isoproterenol. There were also no group differences in blood pressure or heart rate during any procedure. These results suggest that patients with idiopathic Raynaud's disease have increased peripheral vascular alpha-adrenergic receptor sensitivity and/or density compared with normal persons.

Adult↗
PubMed1988

Physiological mechanism of digital vasoconstriction training.

Recent work in our laboratory has shown that vasodilation produced during temperature biofeedback training is mediated through a nonneural, beta-adrenergic mechanism. Here we sought to determine if the effects of feedback training for vasoconstriction are produced through a neural or nonneural pathway and whether other measures of physiological activity are correlated with these changes. Nine normal subjects received temperature feedback vasoconstriction training in which feedback was delivered only during periods of successful performance. In a subsequent session, the nerves to one finger were blocked with a local anesthetic while finger blood flow was recorded from this and other fingers. Vasoconstriction occurred during feedback in the intact fingers but not in the nerve-blocked finger and was accompanied by increased skin conductance and heart rate. These data demonstrate that temperature feedback vasoconstriction training is mediated through an efferent, sympathetic nervous pathway. In contrast, temperature feedback vasodilation training is mediated through a nonneural, beta-adrenergic mechanism.

Adult↗
PubMed1987

The erythrocyte sedimentation rate in end-stage renal failure.

The effect of end-stage renal failure and the dialytic process on erythrocyte sedimentation rate (ESR) is largely unknown. We prospectively studied 60 stable patients with end-stage renal disease to determine the prevalence of elevated ESR in this population. ESRs were also measured immediately pre- and postdialysis in 48 hemodialysis patients. ESR was found to be elevated (greater than or equal to 25 mm/h, Westergren method) in 93% of patients with end-stage renal failure. Fifty-seven percent of patients had marked elevation of ESR (greater than 60 mm/h), while 20% had extreme increases in ESR (greater than or equal to 100 mm/h). In a linear models analysis, aging (P less than .02), anemia (P less than .01), and hypocalcemia (P less than .0001) correlated significantly with ESR elevation. Midweek BUN and creatinine, type and duration of dialysis, cause of renal failure, and serum albumin and total protein measurements did not correlate with ESR. In 48 stable in-center hemodialysis patients, mean predialysis ESR of 70 +/- 4 mm/h was not significantly different from mean postdialysis ESR of 72 +/- 5 mm/h. Retrospective chart review of available ESRs prior to initiation of any dialysis treatment also revealed significant elevation of ESR, mean 82 +/- 9 mm/h, in patients with renal disease not yet on dialysis. An upward trend in ESR during acute illness (74 +/- 9 to 95 +/- 8, N = 10) was observed. In a subpopulation of patients, fibrinogen correlated significantly with ESR while gamma-globulins did not. We conclude that measurement of ESR in end-stage renal failure has little clinical utility. Possible explanations for acceleration of ESR in this population are discussed.

Blood Sedimentation↗
PubMed1986

The neurotoxic effect of gold sodium thiomalate on the peripheral nerves of the rat. Insights into the antiinflammatory actions of gold therapy.

Although gold is one of the few therapeutic agents that has been proven effective in producing remission in patients with rheumatoid arthritis, its mechanism of action is unknown. Since nociceptive afferent and sympathetic efferent fibers of the peripheral nervous system contribute to the pathophysiology of inflammation, and since a known side effect of gold therapy is a polyneuropathy, we tested the hypothesis that gold is toxic to small-diameter peripheral nerve fibers in the rat. We found that prolonged treatment with gold, at the same dosage reported to be effective against adjuvant-induced arthritis in the rat, produced a significant decrease in the numbers of unmyelinated, but not of myelinated, axons. Gold treatment also elevated nociceptive thresholds in both articular and nonarticular structures. These results suggest that gold produces an antiinflammatory effect on arthritis by a neurotoxic effect on the peripheral nerves involved in neurogenic inflammation.

Animals↗
PubMedDate not supplied

Nonneural beta-adrenergic vasodilating mechanism in temperature biofeedback.

Although finger temperature feedback has been used to produce digital vasodilation in normal persons and those with Raynaud's disease, the mechanism and site of this effect have not been studied. In the present investigation, feedback-induced vasodilation was attenuated by brachial artery infusions of propranolol in infused, but not contralateral, hands and was not affected by digital nerve blockade. Quantitative measurements of finger blood flow demonstrated that this vasodilation occurred in arteriovenous shunts in normal persons and in the finger capillary bed in those with Raynaud's disease. Raynaud's disease patients who received finger temperature feedback reported 80 fewer percent symptoms 1 and 2 years after treatment and retained the ability to increase finger temperature and capillary blood flow at these times. These effects were not shown by patients given autogenic training, a relaxation procedure.

Adult↗
PubMedDate not supplied

Plasma catecholamines during behavioral treatments for Raynaud's disease.

We have previously demonstrated that the vasospastic attacks of Raynaud's disease can be induced despite blockade of efferent digital nerves and that feedback-induced vasodilation is mediated through a non-neural, beta-adrenergic mechanism. Here, we sought to determine the role of sympathetic activity, as measured by plasma epinephrine and norepinephrine, during finger temperature feedback and autogenic training. Thirty-one female patients with idiopathic Raynaud's disease were randomly assigned to receive finger temperature feedback or autogenic training over 28 days. Half of each group began and finished training during the follicular phase of the menstrual cycle, the other half during the luteal phase. During training, significant temperature elevations were shown by feedback patients but not by autogenic patients. There were no significant effects for norepinephrine and epinephrine for either group. Cycle phase did not interact with training effects or with catecholamines. These findings do not support the role of decreased sympathetic activation in behavioral treatments for Raynaud's disease.

Adult↗