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Biomedical subjects

R J Woods

Publications and source records attributed to R J Woods.

At least 19 recordsLinked to original sources

Adenosine by aortic flush fails to augment the brain preservation effect of mild hypothermia during exsanguination cardiac arrest in dogs - an exploratory study.

Most trauma cases with rapid exsanguination to cardiac arrest (CA) in the field, as well as many cases of normovolemic sudden cardiac death are 'unresuscitable' by standard cardiopulmonary-cerebral resuscitation (CPCR). We are presenting a dog model for exploring pharmacological strategies for the rapid induction by aortic arch flush of suspended animation (SA), i.e. preservation of cerebral viability for 15 min or longer. This can be extended by profound hypothermic circulatory arrest of at least 60 min, induced and reversed with (portable) cardiopulmonary bypass (CPB). SA is meant to buy time for transport and repair during pulselessness, to be followed by delayed resuscitation to survival without brain damage. This model with exsanguination over 5 min to CA of 15-min no-flow, is to evaluate rapid SA induction by aortic flush of normal saline solution (NSS) at room temperature (24 degrees C) at 2-min no-flow. This previously achieved normal functional recovery, but with histologic brain damage. We hypothesized that the addition of adenosine would achieve recovery with no histologic damage, because adenosine delays energy failure and helps repair brain injury. This dog model included reversal of 15-min no-flow with closed-chest CPB, controlled ventilation to 20 h, and intensive care to 72 h. Outcome was evaluated by overall performance, neurologic deficit, and brain histologic damage. At 2 min of CA, 500 ml of NSS at 24 degrees C was flushed (over 1 min) into the brain and heart via an aortic balloon catheter. Controls (n=5) received no drug. The adenosine group (n=5) received 2-chloro-adenosine (long acting adenosine analogue), 30 mg in the flush solution, and, after reperfusion, adenosine i.v. over 12 h (210 microg/kg per min for 3 h, 140 microg/kg per min for 9 h). The 24 degrees C flush reduced tympanic membrane temperature (T(ty)) within 2 min of CA from 37.5 to approximately 36.0 degrees C in both groups. At 72 h, final overall performance category (OPC) 1 (normal) was achieved by all ten dogs of the two groups. Final neurologic deficit scores (NDS; 0-10% normal, 100% brain death) were 5+/-3% in the control group versus 6+/-5% in the adenosine group (NS). Total brain histologic damage scores (HDS) at 72 h were 74+/-9 (64-80) in the control group versus 68+/-19 (40-88) in the adenosine group (NS). In both groups, ischemic neurons were as prevalent in the basal ganglia and neocortex as in the cerebellum and hippocampus. The mild hypothermic aortic flush protocol is feasible in dogs. The adenosine strategy used does not abolish the mild histologic brain damage.

Adenosine

Spondyloarthropathy identified as the etiology of Nubian erosive arthritis.

Slight variation in manifestation of different diseases may allow a single individual with one disease to mimic the "classic" appearance of another, as evidenced by the frequent confusion of spondyloarthropathy with rheumatoid arthritis. Analysis of population occurrence of arthritis (rather than isolated skeletons) facilitates more precise diagnosis. Northeast Africans living around 2,000 years before present were clearly afflicted with a form of spondyloarthropathy. Lack of inclusion of spondyloarthropathy in the differential diagnosis of erosive arthritis led to past misclassification of Nubians as having rheumatoid arthritis. While evidence of spondyloarthropathy abounds in the literature of human skeletal disease, pre-Columbian Old World rheumatoid arthritis is still elusive. The current study further documents the absence of rheumatoid arthritis in Nubians, supporting the hypothesis that rheumatoid arthritis began in the New World.

Africa, Northern

Hypothermic aortic arch flush for preservation during exsanguination cardiac arrest of 15 minutes in dogs.

BACKGROUND: Trauma victims rarely survive cardiac arrest from exsanguination. Survivors may suffer neurologic damage. Our hypothesis was that a hypothermic aortic arch flush of 500 mL of isotonic saline solution at 4 degrees C, compared with 24 degrees C (room temperature), administered at the start of prolonged exsanguination cardiac arrest (CA) would improve functional neurologic outcome in dogs. METHODS: Seventeen male hunting dogs were prepared under light N2O-halothane anesthesia. The animals were randomized into two groups: group I (n = 9) received 4 degrees C isotonic saline flush and group II (n = 6) received 24 degrees C flush. Two additional dogs received no flush. While spontaneously breathing, the dogs underwent normothermic (tympanic membrane temperature [Ttm] = 37.5 degrees C) exsanguination over 5 minutes to cardiac arrest, assured by electric induction of ventricular fibrillation. After 2 minutes of arrest, the flush was administered over 1 minute into the aortic arch by means of a 13 French balloon-tipped catheter inserted by means of the femoral artery. After 15 minutes of CA, resuscitation was with closed-chest cardiopulmonary bypass, return of shed blood, and defibrillation. For the first 12 hours after CA, core temperature was maintained at 34 degrees C. Mechanical ventilation was continued to 20 hours and intensive care to 72 hours, when final evaluation and perfusion-fixation killing for brain histologic damage scoring were performed. RESULTS: Three dogs in group I were excluded because of extracerebral complications. All 14 dogs that followed protocol survived. During CA, the Ttm decreased to 33.6 +/- 1.2 degrees C in group I and 35.9 +/- 0.4 degrees C in group II (p = 0.002). At 72 hours, in group I, all dogs achieved an overall performance category (OPC) of 1 (normal). In group II, 1 dog was OPC 2 (moderate disability), 3 dogs were OPC 3 (severe disability), and 2 dogs were OPC 4 (coma). Both dogs without flush were OPC 4. Neurologic deficit scores (NDS 0% = normal, 100% = brain death) were 1 +/- 1% in group I and 41 +/- 12% in group II (p < 0.05). The two dogs without flush achieved an NDS of 47% and 59%. Total brain histologic damage scores were 35 +/- 28 in group I and 82 +/- 17 in group II (p < 0.01); and 124 and 200 in the nonflushed dogs. CONCLUSION: At the start of 15 minutes of exsanguination cardiac arrest in dogs, hypothermic aortic arch flush allows resuscitation to survival with normal neurologic function and histologically almost clean brains.

Animals

Cleavage of recombinant human corticotropin-releasing factor (CRF)-binding protein produces a 27-kilodalton fragment capable of binding CRF.

CRF is both a peripheral and a central mediator of inflammation, the activity of which is modified by the presence of a 37-kDa binding protein (CRF-BP). The objective of this study was to measure and characterize this protein in the synovial fluid of rheumatoid arthritis patients and to observe the effects of this inflammatory condition on its structure and properties. Measured by immunoradiometric assays, the mean CRF-BP concentration in synovial fluid from 27 arthritic patients was 0.51 nmol/L (SD = 0.24 nmol/L); that for CRF was 6.31 pmol/L. The mean plasma concentration of CRF-BP in 24 control subjects was 1.38 nmol/L (SD = 0.35 nmol/L) and that for 10 arthritic patients was 2.89 nmol/L (SD = 0.84 nmol/L). Synovial fluids were found by immunoblotting to contain intact CRF-BP and a 10-kDa C-terminal CRF-BP fragment; synovial fluid from healthy controls was not examined. We previously reported that after purification of recombinant CRF-BP, spontaneous cleavage frequently occurs, resulting in a 27-kDa N-terminal and a 10-kDa C-terminal fragment. Because concentrations of native CRF-BP in synovial fluid were insufficient to study the effects of cleavage on ligand binding, they were determined using recombinant human CRF-BP. Tryptophan excitation fluorescence spectra of intact and cleaved recombinant CRF-BP revealed that cleavage was accompanied by conformational change in the N-terminal fragment, leading to exposure of the sole tryptophan residue to polar molecules (emission peak shift from 310 to 250 nm). Using gel filtration chromatography to separate the N- and C-terminal fragments, it was found that the N-terminal fragment of the recombinant protein bound human CRF, although dimerization was somewhat impaired. The C-terminal fragment did not bind CRF. Scatchard analysis confirmed that the affinity of both intact and cleaved CRF-BP for CRF was 1 x 10(10) L/mol. We conclude that synovial fluid contains intact CRF-BP in molar excess to CRF and fragmented CRF-BP. The significance of cleavage and the role of cleavage products have yet to be determined, although they may represent the generation of a novel bioactivity.

Animals

The high degree of internal flexibility observed for an oligomannose oligosaccharide does not alter the overall topology of the molecule.

The conformational properties of oligosaccharides are important in determining their biological properties, such as recognition by proteins. The structural and dynamic properties of many oligosaccharides are poorly understood both because of a lack of experimental data (usually obtained from solution NMR parameters) and because of gross approximations frequently invoked in theoretical models. To characterise the oligomannose oligosaccharide Man,GlcNAc2 we have acquired a more extensive NMR data set and performed the first unrestrained molecular dynamics (MD) simulation in water of this large oligosaccharide (employing the GLYCAM_93 parameter set with the AMBER force field). Good agreement is seen between the computed dynamics data and the results of both an isolated spin pair (ISPA) analysis of short mixing time NOE data and NOE build-up curves for mixing times from 100 to 2000 ms. The number of experimental conformational constraints obtained in this study are in principle sufficient to fully define a rigid structure. The fact that this could not be done indicates a high degree of internal flexibility and/or the presence of multiple conformations about the glycosidic linkages. Independently, the same conclusions are reached from an analysis of the MD results. In addition, the theoretical results allow the overall topology of the molecule and its intra-molecular and solvent-mediated hydrogen bonding pattern to be defined. Extensive re-organisation of solvent and inter-residue hydrogen bonds is shown to be required for significant conformational changes to occur, resulting in relatively long life-times for distinct glycosidic linkage conformations, despite the high local flexibility of the glycosidic linkages. This factor is also seen in the overall topology of the molecule, where the considerable internal flexibility is not translated into gross changes in structure. The control exerted by the solvent over both the flexibility and overall topology of an oligosaccharide has important implications for recognition processes and for the conformational properties of glycans attached to glycoproteins.

Acetylglucosamine

Peritoneal fluid levels of immunoreactive corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) in healthy and endometriosic women.

Corticotropin-releasing factor (CRF) is a 41-amino acid neurohormone involved in the neuroendocrine response to stress, also playing a role in cell-mediated immune functions and in inflammation. In the light of recent evidence showing an association between endometriosis and altered cellular immunity factors, the present study investigates immunoreactive (ir) CRF in the peritoneal fluid of healthy women, and in patients with pelvic adhesions and endometriosis. In addition, peritoneal fluid concentrations of CRF-binding protein (CRF-BP), a 37-kDA protein of 322 amino acids able to modulate central and peripheral CRF functions, were evaluated. Peritoneal fluid samples (n = 35) were collected from healthy women (n = 12), from patients with intrapelvic adhesions (n = 8), and from women with endometriosis (n = 15). In the control group a specimen of blood was collected. Peritoneal fluid and plasma CRF levels were measured by a two-site immunoradiometric assay (IRMA), and CRF-BP levels were measured by a specific radioimmunoassay (RIA). CRF and CRF-BP levels in peritoneal fluid were lower than plasma values, and independent of the phase of the menstrual cycle: in particular, in healthy women there was no significant difference between peritoneal fluid and plasma CRF-BP levels during two phases of the menstrual cycle. Peritoneal fluid levels of CRF and CRF-BP were similar in healthy patients and women with pelvic adhesions or with endometriosis, and when patients with adhesions or with endometriosis were considered as single group, no difference in CRF and CRF-BP levels was noted in comparison to the control group. In patients with endometriosis, no significant differences in peritoneal fluid CRF or CRF-BP levels were recorded, although in patients with stage 2 and stage 3 of the disease peritoneal fluid CRF-BP levels were higher than in healthy patients or in those with a lower grade of the disease. These results suggest that the peritoneal concentration of these hormones may reflect the circulating levels: the absence of any significative variations in peritoneal fluid CRF levels according to the degree of the endometriosis, suggests a limited role of CRF in the immunological changes related to the disease

Adult

The corticotrophin-releasing factor-binding protein: an act of several parts.

Previously the function of hormone binding proteins has been viewed entirely as one of either sequestering ligand activity or of delivering ligand to target tissues. However, some binding proteins have the ability when complexed with ligand to interact directly with target tissues and can undergo considerable post-translational and post-secretional modifications that serve to modify their action. We propose that for the corticotrophin-releasing factor-binding protein (CRF-BP), this adds a further level at which hormonal action may be regulated. This contrasts with previous concepts of a passive role and shows them as important regulators of hormonal action in their own right.

Animals

Computational carbohydrate chemistry: what theoretical methods can tell us.

Computational methods have had a long history of application to carbohydrate systems and their development in this regard is discussed. The conformational analysis of carbohydrates differs in several ways from that of other biomolecules. Many glycans appear to exhibit numerous conformations coexisting in solution at room temperature and a conformational analysis of a carbohydrate must address both spatial and temporal properties. When solution nuclear magnetic resonance data are used for comparison, the simulation must give rise to ensemble-averaged properties. In contrast, when comparing to experimental data obtained from crystal structures a simulation of a crystal lattice, rather than of an isolated molecule, is appropriate. Molecular dynamics simulations are well suited for such condensed phase modeling. Interactions between carbohydrates and other biological macromolecules are also amenable to computational approaches. Having obtained a three-dimensional structure of the receptor protein, it is possible to model with accuracy the conformation of the carbohydrate in the complex. An example of the application of free energy perturbation simulations to the prediction of carbohydrate-protein binding energies is presented.

Carbohydrate Conformation

Analysis of peptides derived from Pro Atrial Natriuretic Peptide that circulate in man and increase in heart disease.

The present investigation was designed to determine the levels and circulating forms of peptides derived from Pro Atrial Natriuretic Peptide (ProANP) and to assess their usefulness as markers for severity of heart disease. A sensitive and specific "two-site" immunoradiometric assay (IRMA) for the measurement of C-terminal ProANP 99-126 (alpha ANP) and two radioimmunoassays (RIAs) for the measurement of N-terminal ProANP 31-67 and ProANP 79-98 were developed. Immunoassays were validated by measurement of circulating peptide concentrations in 15 normal volunteers and 44 patients with varying degrees of heart disease. Mean concentrations of immunoreactive (ir) alpha ANP, ProANP 79-98 and ProANP 31-67 in normal volunteers (n = 15) were 8.5 +/- 1.1, 143 +/- 16 and 587 +/- 83 pmoles/l, respectively, increasing in patients with mild heart disease (NYHA I to II; n = 22) to 17.1 +/- 2.1, 691 +/- 197 and 2160 +/- 540 pmoles/l with greatest increases being observed in patients with severe heart disease (NYHA III to IV; n = 22) of 103 +/- 23, 4550 +/- 590 and 10,600 +/- 1350 pmoles/l, respectively. RP-HPLC of pooled plasma revealed peaks corresponding to alpha ANP, beta ANP, ProANP 1-126, ProANP 1-98, ProANP 31-67 and ProANP 79-98, all apparently increased in heart disease. In conclusion, using a series of immunoassays, we observed the graded increase of alpha ANP, irProANP 31-67 and irProANP 79-98 with increasing severity of heart disease. All peptides proved useful markers, but only ProANP 79-98 levels were able to distinguish patients with mild heart disease (NYHA I) from normals. Finally, RP-HPLC analysis indicated that ProANPs 31-67 and 79-98 circulate as distinct entities, in addition to ProANP 1-98.

Adult

Early feeding after elective open colorectal resections: a prospective randomized trial.

BACKGROUND: A period of starvation after colorectal resections to allow for resolution of the clinical evidence of ileus has been an unchallenged surgical doctrine until recent times. A prospective randomized trial comparing early feeding to traditional management in patients undergoing open elective colorectal resections is reported. METHODS: Patients undergoing elective intraperitoneal colorectal resections without stoma formation were randomized to either an early feeding or control group. The early feeding group were allowed free fluids from 4 h postoperatively progressing to a solid diet from the first postoperative day as they tolerated it. The control group remained nil orally until passage of flatus or bowel motion and were then commenced on fluids progressing to solids over 24-48 h. RESULTS: There were 40 patients in each group well matched for age, sex, type and duration of operation, method of analgesia and mobilization. Thirty-two patients (80%) in the early feeding group tolerated a diet within 48 h. There was no significant difference in the rate of vomiting, nasogastric reinsertion or complications. The early feeding group tolerated a diet, passed flatus, used their bowels, and were discharged from hospital significantly earlier than the control group. CONCLUSION: Early feeding after elective open colorectal resections is successfully tolerated by the majority of patients, leading to earlier resolution of ileus and hospital discharge.

Adult

The pathophysiology of circulating corticotropin-releasing hormone-binding protein levels in the human.

To establish the factors that modulate circulating CRH-binding protein (CRH-BP) levels, we measured plasma CRH-BP in patients with a variety of endocrine and systemic disorders. CRH-BP was measured by RIA. Young women have higher plasma levels of CRH-BP than young men [females (n = 18), mean +/- SEM, 145 +/- 7; males (n = 20), 99 +/- 6 ng/mL; P < 0.0001], but levels do not fall with the menopause or vary during the menstrual cycle and are unaffected by estrogen replacement therapy. Levels were lower in patients with liver disease than in healthy men (26 +/- 3 vs. 99 +/- 6; P < 0.0001) and were elevated in chronic renal failure compared to those in healthy women (211 +/- 11.2 vs. 145 +/- 7; P < 0.01). Levels were unaffected by fasting in men or women (male fasted, 97 +/- 11; male fed, 97 +/- 8; female fasted, 136 +/- 9; female fed, 152 +/- 10). Dexamethasone treatment lowered CRH-BP in all subjects (129 +/- 8 vs. 111 +/- 9; P < 0.003). Similarly, CRH-BP levels were lower in patients with Cushing's syndrome (all female) than in healthy female controls (median, 82; range, 53-106; vs. median, 142; range, 101-190; P < 0.0001). In Cushing's patients, an i.v. bolus of 100 micrograms human CRH further lowered plasma CRH-BP at 15 min (81 +/- 5 vs. 50 +/- 4; P < 0.0003). Plasma levels of CRH-BP are higher in women than men, but this is unrelated to circulating estrogen levels. The low levels in liver disease and the high levels in renal failure support its hepatic origin and the kidneys as the route of clearance from plasma. The ability of glucocorticoids and exogenous CRH to lower plasma CRH-BP levels and of CRH-BP to modulate the bioactivity of circulating CRH suggest that the protein may be an important regulator of circulating CRH or related ligands.

Adult

Bilateral tubal pregnancy. A report of an unusual case.

BACKGROUND: Bilateral tubal pregnancies are rare and are usually confirmed simultaneously during the same operation. We report a case in which the right salpingectomy was performed seven weeks before the left salpingectomy. When the right salpingectomy was done, the left uterine tube appeared entirely normal. CASE: A 38-year-old woman underwent laparoscopic surgery for suspected right tubal pregnancy. A right tubal pregnancy was found to have partially aborted into the peritoneal cavity. The left uterine tube was carefully inspected and appeared normal. Histopathology of the right tube showed products of conception and chorionic tissue. Seven weeks after surgery, the woman presented in hemorrhagic shock necessitating emergency laparotomy and left salpingectomy. Histopathology of the left tube confirmed the presence of chronic tissue. The patient did not have coitus between the two salpingectomies. CONCLUSION: The explanation of the presentation is uncertain. However, this case underscores the importance of careful follow-up of patients after laparoscopic surgery for ectopic pregnancies.

Adult

Inflammatory arthritis in large cats: an expanded spectrum of spondyloarthropathy.

Spondyloarthropathy was documented for the first time in 14 (3.7%) of 386 large cats, affecting eight species belonging to three genera. The limited distribution of joint erosions, associated with spine and sacroiliac joint pathology, was indistinguishable from that occurring in humans with spondyloarthropathy of the reactive type. This form of inflammatory arthritis is almost twice as common as osteoarthritis (for felids as a whole), and animal well-being may be enhanced by its recognition and by initiation of specific treatment.

Acinonyx

NMR and molecular dynamics studies of the conformational epitope of the type III group B Streptococcus capsular polysaccharide and derivatives.

The conformational epitope of the type III group B Streptococcus capsular polysaccharide (GBSP III) exhibits unique properties which can be ascribed to the presence of sialic acid in its structure and the requirement for an extended binding site. By means of NMR and molecular dynamics studies on GBSP III and its fragments, the extended epitope of GBSP III was further defined. The influence of sialic acid on the conformational properties of GBSP III was examined by performing conformational analysis on desialylated GBSP III, which is identical to the polysaccharide of Streptococcus pneumoniae type 14, and also on oxidized and reduced GBSP III. Conformational changes were gauged by 1H and 13C chemical shift analysis, NOE, 1D selective TOCSY-NOESY experiments, J(HH) and J(CH) variations, and NOE of OH resonances. Changes in mobility were examined by 13C T1 and T2 measurements. Unrestrained molecular dynamics simulations with explicit water using the AMBER force field and the GLYCAM parameter set were used to assess static and dynamic conformational models, simulate the observable NMR parameters and calculate helical parameters. GBSP III was found to be capable of forming extended helices. Hence, the length dependence of the conformational epitope could be explained by its location on extended helices within the random coil structure of GBSP III. The interaction of sialic acid with the backbone of the PS was also found to be important in defining the conformational epitope of GBSP III.

Carbohydrate Conformation

Changes in amniotic fluid immunoreactive corticotropin-releasing factor (CRF) and CRF-binding protein levels in pregnant women at term and during labor.

Corticotropin-releasing factor (CRF)-binding protein (CRF-BP) modulates the activity of the hypothalamus-pituitary-adrenal axis during pregnancy, counteracting the actions of circulating or locally produced CRF. The aim of the present study was to evaluate CRF and CRF-BP levels in amniotic fluid of healthy pregnant women during the last 4 weeks of gestation and during spontaneous labor at term. A cross-sectional study was conducted on amniotic fluid collected from pregnant women (n = 68), subdivided into two groups: 1) not in labor (n = 31), and 2) in labor (n = 37). CRF-BP was measurable in all specimens of amniotic fluid, but at 37 weeks of pregnancy the concentration in amniotic fluid was lower (10-fold) than that in maternal plasma (P < 0.01). Pregnant women at 39 and 40 weeks gestation had amniotic fluid CRF-BP levels significantly lower than those at 37 weeks (P < 0.01), and pregnant in women in labor had significantly lower levels than women at term but not in labor (P < 0.01). CRF levels in amniotic fluid and plasma collected in women at 40 weeks gestation not in labor or in labor were significantly higher than those at 37 weeks (P < 0.01). During the last 4 weeks of gestation, amniotic fluid CRF levels in women not in labor did not significantly differ from those obtained at term labor. During the last weeks of pregnancy, amniotic fluid CRF-BP levels decrease and are inversely correlated to CRF levels. The decrease in amniotic fluid CRF-BP at term, augmenting the amount of free CRF, supports the hypothesis that labor is associated with significant changes in local autocrine and paracrine factors that may affect PG release and myometrial contractility, contributing to the mechanism of parturition.

Adult

Heterogeneity of the human corticotropin-releasing factor-binding protein.

Human corticotropin-releasing factor (hCRF), secreted by the placenta, principally in the third trimester, is specifically bound in the peripheral circulation to a 37-kDa binding protein (CRF-BP). This complex is cleared from the circulation. We postulate that the protein may be returned to the blood in a form that is immunologically altered and not well recognized by the reported RIAs. We report that a stable isoform can result from temporary denaturation of recombinant CRF-BP by 8 mol/L urea. This isoform, urea-treated binding protein, which can bind CRF, has been found to bind to an antibody raised against a synthetic peptide comprising the first 24 amino acid residues of CRF-BP, but not to a second similar N-terminal antibody, although it was closely matched in titer. Urea-treated binding protein also cross-reacts poorly in the RIA with CRF-BP. It is proposed that as a result of in vivo post-ligand binding events, isoforms may be susceptible to cleavage. After affinity purification, which involves denaturation, recombinant CRF-BP was often found to be cleaved after storage in the presence of protease inhibitors. Here we present evidence for a C-terminally truncated form of the native binding protein in the plasma of subjects suffering from rheumatoid arthritis, which may parallel the in vitro truncation.

Animals

Dangling practices of 51 nurses: a pilot project.

BACKGROUND: Nurses routinely "dangle" patients to evaluate and promote tolerance to changes in body position and to determine whether the level of activity should progress. Although dangling is a widespread nursing intervention, little research has been done on it, and little is known about how nurses dangle patients. OBJECTIVE: To describe dangling practices reported by critical care and acute care nurses. METHODS: A structured interview tool, developed for the study, was used to interview 51 experienced critical care and acute nurses from seven states about dangling practices. RESULTS: Most respondents said dangling was not routinely ordered and did not require a physician's order. The nurses described numerous strategies they used beforehand to promote tolerance to dangling, for example, premedicating for pain, and multiple interventions they used if patients did not seem to do well during dangling, for example, having patients take slow, deep breaths or move the feet and arms. Indicators of intolerance to dangling included marked changes in blood pressure, heart rate, and level of consciousness and patients' comments such as, "I can't stand it." Estimates of the duration of dangling varied widely, from 1 to 10 minutes; most respondents stated that duration varied "by feel" or depended on the patient's response. The most frequently mentioned personal rule about dangling was, "Get help if you're not sure how the patient will do." CONCLUSIONS: Nurses have developed numerous approaches to dangling acutely ill patients. These approaches should be described and tested to improve nursing practice and patient outcomes.

Acute Disease

Corticotropin releasing factor and its binding protein.

Although the lack of ACTH releasing activity of the high peripheral plasma levels of corticotropin releasing factor (CRF) of human placental origin can now be accounted for by the action of a specific sequestering plasma binding protein (pBP), there are many regions of the brain where the BP is found with little or no overlap with CRF. The existence of a mechanism promoting the rapid disappearance of pBP following bolus injection of exogenous CRF into normal individuals, which is triggered by the formation of a dimer complex (BP2/CRF2), and the elevation of pBP levels found in inflammatory disease, coupled with the lack of unequivocal evidence for endogenous CRF in many of these situations, suggests a role for pBP interaction with ligands other than CRF. We have searched for novel BP ligands in the brain and periphery and have found evidence for them in extracts of sheep brain and in synovial fluid collected from the joints of arthritic patients. These novel BP ligands could, thus, be the peptides responsible for many of the roles currently assigned to brain, peripheral, or immune CRF.

Animals