Heparin therapy and bone fractures.
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Biomedical subjects
Publications and source records attributed to M S Murphy.
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Intestinal dysmotility may be an important factor contributing to various gastrointestinal complications associated with cystic fibrosis. Motilin, enteroglucagon, neurotensin, and peptide YY may each play a role as endocrine hormones influencing gastrointestinal motor activity. Fasting children with cystic fibrosis (N = 8) and controls (N = 18) received a liquid nutrient test meal (fat 4 g/100 ml, protein 4 g/100 ml, carbohydrate 20 g/100 ml, 125 kcal/100 ml; 200 ml/m2) containing lactulose (5 g/100 ml), and the plasma concentrations of these peptides were studied. Mouth-to-cecum transit time was simultaneously studied using the breath H2 technique. Fasting levels of peptide YY and the postprandial response of all four peptides were significantly increased in those with cystic fibrosis. In repeat studies on those with cystic fibrosis after a period of altered pancreatic enzyme supplementation, no significant changes in peptide concentrations were observed. A rise in breath H2 permitting estimation of mouth-to-cecum transit time was noted in 17 control subjects (70-220 min, median 140). In contrast, a rise occurred in only two with cystic fibrosis after low-dose enzyme (70 and 180 min), and four after high-dose enzyme replacement (120-230 min, median 155). Altered gut hormone secretion may play a role in the pathophysiology of intestinal dysmotility in patients with cystic fibrosis.
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Techniques available for the study of lipase activity in the gut are unsatisfactory. Breath tests measuring labelled carbon dioxide (13CO2) may provide a useful means for this assessment. Six subjects with cystic fibrosis and pancreatic insufficiency and 10 controls received a test meal containing [13C] trioctanoin, and breath 13CO2 was measured using a dual inlet, dual detector isotope ratio mass spectrometer. Comparison of postprandial breath 13CO2 enrichment allowed complete separation between children with pancreatic insufficiency and controls. Administration of one capsule of pancreatic enzyme with the test meal resulted in an increase in 13CO2 production in all six patients, and four capsules produced a further increase in five of the six. Serial fat balance studies on four of the patients while receiving comparable doses of oral enzyme failed to demonstrate a progressive improvement in fat absorption. The [13C]trioctanoin breath test may prove a safe, non-invasive technique not only for the detection of pancreatic insufficiency, but also for the quantitative study of intraluminal lipolysis.
The adjustable supination splint is used in select cases in which traditional mobilization therapy is not productive in supination gains. The success of the splint varies depending on many factors, including the type and severity of the injury; the timing of the intervention; the patient's age; and the patient's tolerance of and compliance with the treatment program. The therapist must consult with the physician and have his or her approval before initiating the treatment regimen. Splint use is contraindicated in patients with unstable fractures or with injuries that require surgical intervention before splinting. Therapists should watch for edema, pain, and neurological changes. Depending on the severity of these symptoms, the splint may need to be discontinued or the wearing time and tension adjusted. In our experience at Union Memorial Hospital and in our weighing of the above considerations, we have found favorable results in the use of the adjustable supination splint, with gains in range of motion and function in select patients.
Urinary excretion of lactulose, mannitol, and 3-0-methylglucose, following oral administration (5 g, 5 g, and 2 g, respectively, in 100 ml H2O; 80 ml/m2), has been measured in subjects with cystic fibrosis (CF) (22), Shwachman syndrome (3), chronic pancreatitis (3), and normal controls (46). Mean lactulose excretion was increased 10-fold in CF (p less than 0.001), and two-fold in other disorders associated with pancreatic insufficiency (PI) (p less than 0.05). Mean mannitol excretion was 1.6 times greater in CF (p less than 0.001), compared with controls, but was reduced in other forms of PI (p less than 0.03). The mean lactulose/mannitol excretion ratio was increased in all types of PI (p less than 0.001). There were no significant differences in 3-0-methylglucose excretion. This study confirms the large increase in lactulose absorption recently reported in CF and also demonstrates increased absorption of mannitol; these changes are different than those in other forms of PI. This study provides further evidence for a specific abnormality of the mucosal barrier to the absorption of passively absorbed, water soluble molecules in CF.
Crohn's disease may present insidiously, especially in childhood, and diagnosis may be delayed. In addition, the clinical assessment of the extent of disease activity may be inaccurate. Using mannitol and lactulose as probe molecules we have carried out a cross sectional study of intestinal permeability in patients with active Crohn's disease (n = 17) and control subjects (n = 31). Activity was assessed by an activity index score. The lactulose:mannitol urinary excretion ratio was significantly increased in Crohn's disease. Overall sensitivity was 82%, and 92% when activity was moderate or severe. When permeability was compared with the activity index there was a significant correlation among patients. In five patients studied longitudinally a significant correlation was also present. Measurement of intestinal permeability is non-invasive, and may be useful both as a screening test in patients with non-specific symptoms, and for the assessment of the extent of disease activity in patients with Crohn's disease.
Achalasia of the cardia, a disorder associated with degenerative loss of esophageal myenteric ganglion cells, is reported in association with a recently described progressive neurological disorder, "early onset cerebellar ataxia with retained reflexes." This form of cerebellar ataxia is thought to be inherited as an autosomal recessive disorder. The occurrence of these two very rare neurodegenerative disorders in a single individual is of interest because of the potential genetic and pathogenetic implications of the association.
We have examined the interrelationships among CaO2, blood flow, oxygen binding by hemoglobin, and VO2 in cardiac patients with and without chronic cardiac decompensation. We have quantified the role that decreased oxygen-binding to hemoglobin may play in maintaining VO2 in the presence of low systemic blood flow rates. The volume rate of oxygen delivery to tissues was expressed as the OFIa, the product of CO2 and blood flow. OFIa varied from 738 to 262 ml/min/m2, whereas VO2 varied from 170 to 117 ml/min/m2. Thus, in the patients with lowest OFIa (63% below the highest OFIa), VO2 was only down 19%. VO2 was maintained because the extraction of oxygen rose from about 20% to 50% in close association with the decrease in OFIa. Oxygen binding to hemoglobin was lower in patients with the lowest OFIa--and therefore, at in vivo conditions of pH, PCO2, and temperature, P50 in vivo was higher. The resulting facilitation of oxygen release at the PO2 of tissue capillaries could explain about one third of the observed increment in oxygen extraction in patients with low OFIa. An alternative interpretation is that a high P50 in vivo minimizes the reduction in PVO2 needed to maintain VO2 when increased proportional extraction of O2 compensates for decreased OFIa.
The detection of high- or low-affinity hemoglobins in subjects with polycythemia or anemia is difficult for most physicians because of the requirement for special equipment to do oxygen-hemoglobin dissociation curves. Measurement of the pH, oxygen tension, and oxygen saturation of antecubital venous blood with instruments present in most clinical chemistry laboratories permits an estimate of the strength of oxygen binding to hemoglobin. An equation can be used to convert the venous oxygen tension (standardized to pH 7.4) and the oxygen saturation to the P50 of the oxygen-hemoglobin dissociation curve on which the observed point falls. The data indicate that this method is a reliable initial step in the identification of a hemoglobin with abnormal affinity for oxygen and may be applied to population studies, since reliable results are obtained with venous blood stored at 4 degrees C for up to 24 hours.
The effect of water-soluble radiographic contrast material on pH when added to blood in clinical dosages in vitro or when used in vivo for diagnostic purposes was examined. Contrast material caused a reduction of blood pH. The mechanism of this occurence was found to be the balancing of the negative charge of intracellular organic anions by the extracellular anionic contrast material molecules. The normal negative potential of about 10 mV across the red cell membrane was reduced, nullified, or reversed depending on the concentration of contrast material added to blood. As the inside of the cell became more positive with respect to the outside, protons were, in effect, repelled into plasma, although the apparent exodus of protons occurs by the generation and outward diffusion of carbon dioxide. Since the acidemia is dependent on rehydration of carbon dioxide in plasma, a reaction measured in seconds, the site of injection and transit time of dye will contribute to the pH of the plasma during passage through a regional capillary bed. We speculate that an alteration in membrane potential and/or the acute acidemia may contribute to the adverse effects of contrast material, particularly on tissues dependent on membrane electrical rhythmicity such as the myocardium.
Radiographic contrast materials added to blood reduce the red cell membrane potential by balancing the internal impenetrable anions, hemoglobin and organic phosphates. In so doing, a redistribution of protons occurs such that plasma is acidified. The time course of acidification of plasma is measured in seconds, with a nadir of pH occurring 12 to 15 seconds after addition of Hypaque (1.5 to 3.0 ml/10 ml blood) and a half-time of acidification requiring about 6 seconds. The acidification process is slowed in part by an initial alkalosis due to Hypaque. The acidification of blood is more rapid after addition of Renografin (1.5 to 3.0 ml/10 ml blood) than after addition of Hypaque since the former solution is slightly acidic. The time course of plasma acidification indicates that a maximal reduction in blood pH may not occur in the capillaries of a regional circulation following injection of contrast materials into its afferent vessel, since the transit time of the contrast material may be less than the time required for maximal acidification of plasma.