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Biomedical subjects

H A Thomas

Publications and source records attributed to H A Thomas.

At least 19 recordsLinked to original sources
PubMed2000

Indomethacin tocolysis and risk of necrotizing enterocolitis.

OBJECTIVE: To investigate the possible association of indomethacin tocolysis with neonatal necrotizing enterocolitis. METHODS: A case-control study was performed for the period November 1, 1997, through May 1, 1999. All cases of proven necrotizing enterocolitis were ascertained, and four controls for each case were randomly identified from all Special Care Nursery admissions before 37 weeks' gestation without necrotizing enterocolitis during that same period. RESULTS: During the 18-month period there were 24 cases of necrotizing enterocolitis out of 10,200 deliveries. Infants with necrotizing enterocolitis were more preterm (29.7 +/- 3.9 compared with 32.7 +/- 6.0 weeks; P =.03) and had lower birth weights (1453 +/- 777 compared with 1820 +/- 678 g; P =.02) compared with controls (n = 96). Respiratory distress syndrome (RDS) and sepsis were both significantly associated with an increased risk of necrotizing enterocolitis: 16 of 24 cases compared with 40 of 96 controls had RDS (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.0, 8.3) and 14 of 24 cases compared with 11 of 96 controls were septic (OR 10.8, 3.4, 95% CI 34.2). Indomethacin as a single agent was not associated with necrotizing enterocolitis (OR 1.0, 95% CI 0.2, 4.8). Using a logistic regression model, necrotizing enterocolitis was strongly associated with sepsis (adjusted OR 8.5, 95% CI 2.2, 32.5). When sepsis was removed from the model, double-agent tocolytic therapy was significantly associated with necrotizing enterocolitis (adjusted OR 6.9, 95% CI 1.1, 43.6). CONCLUSION: Tocolysis with indomethacin as a single agent was not associated with necrotizing enterocolitis in this case-control study. Combination tocolytic therapy may be a marker for subclinical infection and not causally related to necrotizing enterocolitis.

Adult↗
PubMed2000

Emergency medicine residents' shiftwork tolerance and preference.

OBJECTIVES: To determine the shift lengths currently worked by emergency medicine (EM) residents and their shift length preferences, and to determine factors associated with EM residents' subjective tolerance of shiftwork. METHODS: A survey was sent to EM-2 through EM-4 allopathic EM residents in May 1996. This questionnaire assessed the residents' shift length worked, shift length preferences, night shift schedules, and self-reported ability to overcome drowsiness, sleep flexibility, and morningness-eveningness tendencies. When providing shift length preferences, the residents were asked to assume a constant total number of hours scheduled per month. RESULTS: Seventy-eight programs participated, and 62% of 1,554 eligible residents returned usable surveys. Current shift lengths worked were 8 hours (12%), 10 hours (13%), 12 hours (37%), combinations of 8-hour, 10-hour, or 12-hour (34%) shifts, and other combinations (4%). Seventy-three percent of the respondents indicated that they preferred to work 8-hour or 10-hour shifts, and only 21% preferred a 12-hour shift. Shiftwork tolerance was recorded as: not well at all (2%), not very well (14%), fairly well (70%), and very well (14%). The EM residents' eveningness preference, ability to overcome drowsiness, sleep flexibility, younger age, and having no children at home were all associated with greater shiftwork tolerance. CONCLUSIONS: Emergency medicine residents generally tolerate shiftwork well and prefer 8-hour or 10-hour shift lengths compared with 12-hour shift lengths. Emergency medicine residencies with 12-hour shifts should consider changing residents' shifts to shorter shifts.

Adult↗
PubMed1999

The occupational risk of motor vehicle collisions for emergency medicine residents.

OBJECTIVE: To determine the prevalence and risk factors associated with motor vehicle collisions (MVCs) and near-crashes as reported by emergency medicine (EM) residents following various ED shifts. METHODS: A survey was sent to all allopathic EM-2-EM-4 residents in May 1996 asking whether they had ever been involved in an MVC or near-crash while driving home after an ED shift. The residents' night shift schedules, self-reported tolerance of night work, ability to overcome drowsiness, sleep flexibility, and morningness/eveningness tendencies also were collected. RESULTS: Seventy-eight programs participated and 62% of 1,554 eligible residents returned usable surveys. Seventy-six (8%, 95% CI = 6% to 10%) residents reported having 96 crashes and 553 (58%, 95% CI = 55% to 61%) residents reported being involved in 1,446 near-crashes. Nearly three fourths of the MVCs and 80% of the near-crashes followed the night shift. Stepwise logistic regression of all variables demonstrated a cumulative association (R = 0.19, p = 0.0004) that accounted for 4% of the observed variability in MVCs and near-crashes. Univariate analysis showed that MVCs and near-crashes were inversely related to residents' shiftwork tolerance (p = 0.019) and positively related to the number of night shifts worked per month (p = 0.035). CONCLUSIONS: Residents reported being involved in a higher number of MVCs and near-crashes while driving home after a night shift compared with other shifts. Driving home after a night shift appears to be a significant occupational risk for EM residents.

Accidents, Traffic↗
PubMed1998

Bipolar-shape response of human neutrophils to corticotropin-releasing factor.

Human neutrophils in whole blood become bipolar in shape after exposure to chemokinetic stimuli. In normal blood, the proportion of non-spherical neutrophils was 1.2 +/- 0.07% (n = 101). After incubation of blood samples with corticotropin-releasing hormone (CRF, 1 to 20 microM) 36 of 101 subjects exhibited a > or = 10% bipolar-shape ellipsoid response. This ellipsoid response was more frequent in female than in male subjects (32/75 vs. 4/26, p < 0.01). Female Caucasian subjects were more sensitive to CRF than female East Asian subjects (25/48 vs. 2/15, p < 0.01). Age was not a factor in sensitivity to CRF. In young female East Asian subjects (23 +/- 0.4 years, n = 8) that did not manifest the ellipsoid response to CRF, formyl-Met-Leu-Phe (fMLP), a chemotactic peptide, 10(-9) M increased non-spherical neutrophils to 31 +/- 0.8%. In these individuals, the fMLP response was inhibited in a dose-dependent manner by CRF. The pharmacological profile of the stimulatory and fMLP-inhibitory actions of CRF on neutrophil shape was consistent with that of a CRF1-receptor mediated response. Expression of mRNA for the CRF1-receptor was detected in hematopoietic cell lines (e.g., HL-60) using a reverse transcriptase polymerase chain-reaction method. The bipolar-shape response of human neutrophils to CRF has the potential to be a useful indicator of the functional state of this hormone-receptor system in inflammation.

Adult↗
PubMed1998

Dynorphin A(6-12) analogs suppress thermal edema.

Dynorphin A (Dyn A) is a 17-residue opioid peptide derived from prodynorphin precursors found in mammalian tissues. Removal of Tyr1 from Dyn A produces a peptide that is more potent than Dyn A in attenuating the acute phase of the inflammatory response, as measured by inhibition of heat-induced edema in the anesthetized rat's paw (exposure to 58 degrees C water for 1 min). Dyn A(2-17), however, no longer interacts with opioid receptors. It was postulated that the non-opioid anti-inflammatory actions of Dyn A(2-17) may reside in Dyn A(6-12); that is, Arg-Arg-Ile-Arg-Pro-Lys-Leu. here we report on the activities of Dyn A(6-12) analogs modified by substitutions on the N terminus, by single N-methyl substitution and by single replacement of residues by alanine. The results indicated that the minimal sequence required for an anti-edema ED50 of <1.0 micromol/kg i.v. was anisoyl-Arg6-Arg7-Xaa8-Arg9-Pro10)-Xaa11-+ ++Xaa12-NH2. A prototype, p-anisoyl-[D-Leu12] Dyn A(6-12)-NH2, with an ED50 of 0.20 micromol/kg i.v. compared to an ED50 of 0.08 micromol/kg i.v. for Dyn A(2-17), was selected for further tests of biological activity. This analog, like Dyn A(2-17), lowered blood pressure in anesthetized rats. In a model of neurogenic inflammation, produced by antidromic stimulation of the vagus in the anesthetized rat, p-anisoyl-[D-Leu12] Dyn A(6-12)-NH2, 0.23 micromol/kg i.v., attenuated the negativity of tracheal tissue interstitial pressure (Pif), which normally develops after nerve stimulation. Modulation of interstitial pressure may be the mechanistic basis for the anti-edema properties of these Dyn A(6-12) analogs.

Animals↗
PubMed1998

D-amino acid-substituted analogs of corticotropin-releasing hormone (CRH) and urocortin with selective agonist activity at CRH1 and CRH2beta receptors.

The activities of corticotropin-releasing hormone (CRH)-related peptides and several analogs were examined in cells transfected with either CRH1 or CRH2beta receptors, in suppression of heat-induced rat paw edema in pentobarbital-anesthetised animals and in stimulation of release of immunoreactive corticotropin (ir-ACTH) from rat anterior pituitary tissue in vitro. The peptides tested were human/rat (h/r)-CRH, r-urocortin, h-urocortin, white sucker fish or maggy sole urotensin I and some analogs of these peptides substituted with D-amino acids at residues 4 (urocortin), 5 (CRH and urotensin I) and 20 (CRH). In cells transfected with CRH1 receptors, these peptides were similar in potency in stimulation of cAMP accumulation. By contrast, at CRH2beta receptors peptides of the urocortin and urotensin series were more potent than h/r-CRH while [D-Glu20]-h/r-CRH was 6.5-fold less active than h/r-CRH. I.v. administration of h/r-CRH or related peptides 10 min prior to a thermal stimulus produced a significant dose-dependent inhibition of rat paw edema formation. Comparison of the ED50's showed that urocortins ([D-Ser4]-h-urocortin, h-urocortin, [D-Pro4]-r-urocortin, r-urocortin) were approximately 2 to 3 times more active than h/r-CRH, but [D-Glu20]-h/r-CRH was 18.5-fold less active. In the assay for ir-ACTH release, the activity of h/r-CRH and [D-Glu20]-h/r-CRH was similar but [D-Pro5]-h/r-CRH and [D-Pro4]-r-urocortin was less potent than the native peptide. These results provide further evidence that D-amino acid substitution at residue 20 reduces the potency of h/r-CRH at endogenous (anti-edema effect) and transfected (cAMP accumulation) CRH2beta receptors whilst activity at the CRH1 receptor is retained (ACTH-release and cAMP accumulation). On the other hand substitutions at residues 4 or 5 in r-urocortin or h/r-CRH respectively appear to decrease activity at CRH1 but not CRH2beta receptors The modified CRH and urocortin analogs described here may provide clues for the further design of receptor selective ligands.

Adrenocorticotropic Hormone↗
PubMed1998

Anti-inflammatory mystixin peptides inhibit plasma leakage without blocking endothelial gap formation.

Mystixins are synthetic peptides that inhibit plasma leakage after tissue injury. We sought to determine the mechanism of the antileakage effect of mystixins, with particular reference to the formation of endothelial gaps in postcapillary venules. Intravenous administration of mystixin-7, a prototype heptapeptide (p-anisoyl-Arg-Lys-Leu-Leu-D-Thi-Ile-D-Leu-NH2), decreased Evans blue leakage induced by substance P (5 microg/kg i.v.) with an ED50 (95% confidence limits) of 130 (76-211) microg/kg in trachea and 52 (27-100) microg/kg in skin of anesthetized F344 rats. Leakage was decreased without a reduction in the number or size of endothelial gaps, visualized by silver deposits after silver nitrate staining. The number of silver deposits per tracheal endothelial cell was 11.4 +/- 0.2 (mean +/- S.E.) after vehicle pretreatment vs. 13.0 +/- 0.8 after mystixin-7 pretreatment (100 microg/kg i.v.). Silver deposit diameter was unchanged at 1.4 +/- 0.1 micron. Mean arterial blood pressure dropped by a maximum of 38% from baseline for approximately 10 min after mystixin-7 (100 microg/kg i.v.), then recovered to a plateau at about 13% below baseline. The antileakage effect of mystixin-7 pretreatment in vivo was also demonstrated in aldehyde-fixed vessels perfused in situ with Evans blue at constant flow (skin, 79% reduction; trachea, 49% reduction), which suggests that mystixin can reduce leakage independent of its hypotensive effect. We conclude that the antileakage effect of mystixin does not depend on reducing the number or size of endothelial gaps, but instead could be caused by residual hypotension, which reduces the negative interstitial fluid pressure toward zero, or clogging of endothelial gaps.

Animals↗
PubMed1996

[D-Pro5]Corticotropin-releasing factor analogs as selective agonists at corticotropin-releasing factor receptors.

Corticotropin-releasing factor (CRF) acts on at least two types of CRF receptors. To search for selective CRF receptor agonists, 37 ovine CRF analogs, systematically substituted with D-amino acids, were tested for inhibitory activity on edema induced in the pentobarbital-anesthetized rat paw by heat (immersion in 58 degrees C water for 1 min). The activity of each analog, administered 21 nmol/kg i.v. 10 min before heat, was compared to published data on the analog's potency in stimulating adrenocorticotropin (ACTH) release from cultured rat pituitary cells. In general, a positive rank correlation was found between the anti-edema and neuroendocrine activities of these analogs, however, one outlier, [D-Pro5]ovine CRF, exhibited greater selectivity for anti-edema activity. The human/rat analog of [D-Pro5]CRF was synthesized and found to be equipotent to human/rat CRF for suppression of heat-edema. In cells transfected with two types of cloned CRF receptors, the intracellular cAMP response to [D-Pro5]human/rat CRF was equipotent to human/rat CRF in the heart-muscle CRF (CRF2 beta) receptor assay but was five times less potent than human/rat CRF in the pituitary-central nervous system CRF (CRF1) receptor assay. We conclude that changing residue Pro5 in the CRF molecule from a L- to a D-configuration confers selectivity by decreasing second messenger activation at the CRF1 receptor whilst retaining full potency at the CRF2 beta receptor.

Adrenocorticotropic Hormone↗
PubMed1996

Radiologic investigation and treatment of gastrointestinal fistulas.

Diagnostic radiology has assumed an increasingly prominent role in the diagnosis, investigation, and treatment of gastrointestinal fistulas during the past 15 years. This development largely has been the result of the application of computed tomography and ultrasonography to the diagnosis of intra-abdominal inflammatory processes and the use of these cross-sectional imaging modalities to guide percutaneous abscess drainage by the interventional radiologist. Effective percutaneous techniques have been developed that allow many gastrointestinal fistulas to be managed nonoperatively with less morbidity and mortality.

Catheterization↗
PubMed1995

Potent inhibition of thermal edema in rat by des-Tyr-Dynorphin A.

In an earlier study, dynorphin A(1-13) [Dyn A(1-13)] was shown to inhibit heat-induced edema in the anesthetized rat's paw but the potency of this action was low, with effective doses in the range of 3-4 mg/kg i.v. In this study, Dyn A and related fragments were tested. Thermal edema was elicited in anesthetized male albino rats by immersion of the hindpaw in 58 degrees C water for 1 min. The median effective dose (ED50 and 95% confidence limits) in mg/kg i.v. for inhibition of edema were: Dyn A, Dyn A(2-17), and Dyn A(1-13), 1.7 (1.2-2.4), 0.15 (0.09-0.24), and 3.2 (1.9-5.5), respectively. The ED50 values of [D-Ala2]Dyn A, [D-Ala2]Dyn A(2-17), and [D-Ala2]Dyn A(2-17)-amide were found to be 0.92 (0.40-2.10), 1.25 (0.60-2.63), and 0.65 (0.36-1.16) mg/kg i.v., respectively. Dyn A(2-17), 0.5 mg/kg i.v., also inhibited pulmonary edema produced by i.v. injection of epinephrine. The anti-edema action of Dyn A(2-17) was not blocked by naloxone, an opioid receptor antagonist, or dependent on the hypotensive action of this peptide. It is postulated that the antiedema activity of Dyn A resides in the core fragment Dyn A(6-12). Two peptides, N-acetyl-Dyn A(6-12)-amide and N-acetyl-[D-Leu12]Dyn A(6-12)-amide, were synthesized and, when tested, were effective in reducing thermal edema with ED50 values of 1.4 (0.6-3.7) and 2.2 (1.2-4.1) mg/kg i.v., respectively.

Amino Acid Sequence↗
PubMed1994

Correlation of neuroendocrine and anti-edema activities of alanine-corticotropin-releasing factor analogs.

Thirty-three ovine corticotropin-releasing factor (CRF) analogs, systematically substituted with alanine (Ala) residues, were tested for inhibitory activity on edema induced in the pentobarbital-anesthetized rat paw by heat (immersion in 58 degrees C water for 1 min). The activity of each analog, administered 0.1 mg/kg i.v. 10 min before heat, was compared to the rank order of the analog's potency in stimulating adrenocorticotropin (ACTH) release from cultured rat pituicytes. A strong positive rank correlation was found between the anti-edema and neuroendocrine activities of these analogs.

Adrenocorticotropic Hormone↗
PubMed1994

Embolization of multiple Rasmussen aneurysms as a treatment of hemoptysis.

A 40-year-old man with a history of tuberculosis developed massive hemoptysis. Embolization of a bronchial artery branch did not resolve the bleeding. Selective angiography eventually revealed three pseudoaneurysms arising from an apical segmental branch of the right pulmonary artery, two of which were successfully embolized with coils. The patient's hemoptysis resolved within 48 hours. Although most patients with hemoptysis and active tuberculosis bleed from the bronchial circulation, the pulmonary arterial circulation should be immediately evaluated if the bronchial angiogram is normal. Coil embolization is a safe and effective means of treating these pseudoaneurysms.

Adult↗
PubMed1993

CRF and related peptides as anti-inflammatory agonists.

The permeability of endothelial surfaces increases in response to injury. We have shown that vascular leakage in experimental models of tissue injury can be inhibited by CRF and by a novel class of peptides that we call mystixins. Binding sites for iodinated-Tyro-CRF have been revealed in mucous membranes, and immunoreactive CRF-like materials have been found in inflamed tissues. Perhaps the breakdown of cytoskeletal intermediate filaments after insult generates or exposes peptide domains similar to mystixins. Endogenous CRF-like or mystixin-like peptides, if activated or released locally in injured tissues, may function as agonists to counteract the immediate inflammatory response. If this is so, the peripheral actions of these peptides add a new dimension to the idea that CRF and related substances organize and regulate an organism's response to stress.

Amino Acid Sequence↗
PubMed1993

Peripheral anti-inflammatory actions of corticotropin-releasing factor.

Swelling, oedema, and loss of fluids and protein from the vascular compartment are immediate responses seen in living tissues after severe injury. Peptides of the corticotropin-releasing factor (CRF) superfamily have the unusual property of preventing the vascular leakage that occurs in tissues after damage. For example, CRF decreased protein extravasation, oedema and swelling in the anaesthetized rat's paw after exposure to heat or to extreme cold, in tracheal mucosa after exposure to formaldehyde, in skeletal muscle after a knife cut, and in brain cortex after freezing. The anti-inflammatory actions of CRF were independent of steroid release or hypotensive effects. CRF was a functional antagonist of inflammatory mediators such as histamine and substance P. It inhibited neurogenic inflammation, but interactions with unmyelinated sensory neurons did not account for the wide range of CRF's anti-inflammatory activities. Localized application of CRF prevented histamine-induced leaks in the hamster cheek pouch, and displaceable binding sites to iodinated CRF were found on blood vessels and on epithelial cells in close proximity to sites of vascular leakage. These results indicated peripheral sites of action. CRF may be the first example of a peptide hormone demonstrated to have potent anti-inflammatory agonist actions in vivo.

Animals↗
PubMed1993

Unilateral emboli in a patient with thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura is a rare disease most commonly associated with microangiopathic hemolytic anemia, thrombocytopenia, fever, neurologic disorders, and renal dysfunction. We describe a patient with a history of thrombotic thrombocytopenic purpura that had been quiescent for 4 months; he had a 3-week history of painful purpuric lesions on the left hand only. He also had mottling and a livedoid purpura of the distal fingertips, splinter hemorrhages of the left fingernails, and a decreased radial pulse. Findings of a biopsy specimen revealed multiple capillary and small vessel thromboses. Contrast aortography demonstrated a pseudoaneurysm of the proximal descending thoracic aorta with stenosis of the left subclavian artery at its origin and an associated thrombus.

Adult↗
PubMed1993

Novel anti-inflammatory undecapeptides that contain anisolyated glutamic acid derivatives.

In various animal models of tissue injury, corticotropin-releasing factor (CRF) and related peptides inhibit swelling, edema and loss of protein from the vascular compartment. To search for smaller peptide segments of CRF that might retain anti-inflammatory activity, the authors tested peptides similar to the carboxy terminals of ovine (o) and human/rat (h/r) CRF. Also, because h/rCRF(35-39), -Arg-Lys-Leu-Met-Glu-, resembles Arg-Lys-Leu-Leu-Glu-, a sequence found in many intermediate filament proteins, analogous peptides were evaluated. Ovine CRF(21-41), -Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys- Leu-Asp-Ile-Ala-NH2, its carboxy terminal carboxyl derivative, oCRF(21-41)-OH, and the fragments, oCRF(26-41) and oCRF(30-41), were inactive when assayed at 5 mg/kg i.v. on edema induced in the pentobarbital-anesthetized rat's hindpaw after immersion in 58 degrees C water for 1 min. Crude peptides, D-Leu-Ala-Thr-D-Tyr-Arg-Lys-Leu-Leu-Glu-Ile-D-Leu-NH2 and D-Ala-His-Ser-D-Asn-Arg-Lys-Leu-Leu-Glu-Ile-D-Leu-NH2, were found to have activity in this bioassay. Characterization of the structures within the crude mixture revealed that substitution of the glutamic acid residue with an anisolyated glutamic acid (2-amino-5-(methoxyphenyl)-5-oxopentanoic acid) derivative, designated as (A*), increased the overall potency. The glutamyl-anisole derivative was a by-product of the temperature-dependent Friedel-Crafts acylation reaction that occurs during hydrogen fluoride cleavage of glutamyl-containing peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗