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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 325 records · Page 18Linked to original sources
PubMed1991

Nasal continuous positive airway pressure facilitates extubation of very low birth weight neonates.

A prospective randomized trial was performed in 58 neonates comparing nasal continuous positive airway pressure (NCPAP) vs oxyhood following extubation of neonates weighing less than 1 kg. All neonates had been ventilated for the treatment of respiratory distress syndrome for at least 24 hours and weighed less than 1 kg at the time of extubation. Clinical criteria for elective extubation included improving pulmonary status, fraction of inspired oxygen (FIO2) less than or equal to 0.35, mean airway pressure less than or equal to 7 cm H2O, ventilator rate less than or equal to 20 breaths per minute, and weight at least 80% of birth weight. Informed consent was obtained and neonates were randomized to NCPAP or oxyhood following extubation. Success was defined as remaining free of additional ventilatory support for at least 5 days. Failure criteria included FIO2 greater than or equal to 0.60 to maintain pulse oximetry greater than or equal to 93%, PaCO2 greater than or equal to 60 mm Hg, pH less than or equal to 7.23, or moderate to severe apnea. Results demonstrate that 22 (76%) of 29 neonates were successfully extubated to NCPAP while only 6 (21%) of 29 were successfully extubated to oxyhood (P less than .0001). There were no differences in baseline characteristics between the two groups. Of the 23 neonates who failed oxyhood, 21 were then given a trial of NCPAP and 58% (12/21) remained extubated. Data indicate that using selected clinical criteria for elective extubation of neonates weighing less than 1 kg, NCPAP facilitates successful extubation.

Humans↗
PubMed1991

Surfactant treatment of full-term newborns with respiratory failure.

Surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full-term newborns. Fourteen full-term newborns with respiratory failure associated with pneumonia (7 patients) and meconium aspiration syndrome (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given intratracheally up to every 6 hours for a maximum of four doses. The group mean fraction of inspired oxygen (FI02) before treatment was 0.99 +/- 0.01 SEM, and the mean airway pressure (MAP) was 14.6 +/- 1.0 cm H2O. Patients showed significant improvement in oxygenation after initial surfactant treatment, with the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 +/- 0.01 before surfactant treatment to 0.22 +/- 0.05 by 15 minutes (P = .03) and remaining improved for 6 hours. The oxygenation index, incorporating MAP as well as oxygen variables, also improved significantly from 26.2 +/- 3.1 to 11.2 +/- 1.7 at 15 minutes (P less than .001), with improvement sustained for more than 6 hours. Chest radiographs were blindly scored from 0 (normal) to 5 (severe opacification), and these improved with marginal significance after initial surfactant treatment (from 2.9 +/- 0.2 to 2.5 +/- 0.2, P = .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

RPE, blood glucose, and carbohydrate oxidation during exercise: effects of glucose feedings.

This study examined the effects of glucose ingestion on differentiated and undifferentiated ratings of perceived exertion (RPE) during prolonged cycling exercise. On two occasions, seven trained males cycled for 180 min on a Monark cycle ergometer at 70% peak VO2 (VO2peak). Subjects consumed an 8% glucose/electrolyte drink (G) or a flavored water placebo (P) every 15 min throughout exercise. Measurement of RPE, ventilation (VE), oxygen uptake (VO2), respiration rate (RR), respiratory exchange ratio (RER), heart rate (HR), and venous blood sample collection preceded ingestion of the drink. Subjects were homogenous with respect to height, weight, and VO2peak. RPE for the legs and overall body were significantly attenuated (P less than 0.05) during the last 45 min of exercise. Plasma glucose and insulin were higher (P less than 0.05) in G than in P at virtually all time points. CHO oxidation and work rate were maintained throughout exercise in G but not during the last 30 min of exercise in P (P less than 0.05). Percent changes in plasma volume, plasma lactate, HR, VE, RR, and RPE for the chest were not different between conditions (P greater than 0.05). The data suggest that ingestion of carbohydrate beverages during endurance cycling can maintain plasma glucose and CHO oxidation during the latter stages of prolonged exercise. As a result, it appears that a relationship exists between attenuation of ratings of perceived exertion (especially in the legs), blood glucose, and CHO oxidation late in prolonged exercise. The mechanism for this probably involves the increased availability of blood-borne glucose to serve as substrate for brain and/or muscle energy metabolism during a time when endogenous stores of carbohydrate are low.

Analysis of Variance↗
PubMed1991

Increased neutrophil mobilization and decreased chemotaxis during cortisol and epinephrine infusions.

Although hormones are putative mediators of neutrophil changes after injury, the effects of trauma-induced levels of plasma cortisol and epinephrine on circulating neutrophils have not been reported in humans. The dynamics of PMN mobilization and chemotaxis were evaluated during 19 infusions of epinephrine or cortisol or a combined infusion of both hormones in ten normal volunteers. Basal levels of epinephrine and cortisol increased during infusions to levels consistent with those reported following severe injury. Circulating neutrophil counts increased in parallel with plasma cortisol levels. Epinephrine mobilized the entire marginated pool of neutrophils, and the neutrophil half-life was extended from a normal of 6.6 hours to 10.4 hours by cortisol. Chemotaxis after six hours of epinephrine infusion was reduced compared with baseline chemotaxis. In four volunteers who had a second infusion of cortisol, chemotaxis was significantly depressed ten days after the infusion compared with baseline. From these data we conclude that stress levels of epinephrine mobilize the marginated pool of granulocytes into the circulating pool in a linear fashion, and cortisol raises the half-life of circulating neutrophils. Reduced neutrophil chemotaxis seen as a consequence of these infusions could account for some of the increased susceptibility to infection that occurs after major trauma.

Chemotaxis, Leukocyte↗
PubMed1991

Analysis of factors predicting speed of hematologic recovery after transplantation with 4-hydroperoxycyclophosphamide-purged autologous bone marrow grafts.

We previously described the predictive value of graft colony-forming units granulocyte macrophage (CFU-GM) content after 4-hydroperoxycyclophosphamide (4-HC) purging for the duration of aplasia after autologous bone marrow transplantation. Despite the uniform 4-HC concentration, we observed heterogeneity in CFU-GM survival and the kinetics of engraftment. We have now analysed patient and graft characteristics for 154 patients undergoing autologous transplantation with 4-HC purged grafts to further define this heterogeneity. Patients transplanted for the treatment of malignant lymphoma reached a peripheral blood granulocyte count of greater than 0.5 x 10(9)/l (median, 20 versus 40 days; p less than 0.001) and platelet transfusion independence (median, 30 versus 70 days; p less than 0.001) significantly faster than patients transplanted for acute non-lymphoblastic leukemia. Other diagnostic groups were intermediate. These differences were independent of graft CFU-GM content. Multiple other patient and graft factors including patient age, peripheral blood counts on day of harvest, and amounts of other hematopoietic progenitors also predicted the kinetics of engraftment in univariate and multivariate analysis. Cytomegalovirus infection during the aplastic period predicted a delay in granulocyte (p = 0.024) but not platelet recovery (p = 0.174). This analysis demonstrates that multiple patient, graft, and post-transplant factors predict the engraftment capacity of autografts, and the kinetics of engraftment with 4-HC purged grafts. The multiple predictive factors explain a significant portion of the variability in engraftment kinetics observed after transplantation with 4-HC purged autografts.

Adolescent↗
PubMed1990

Platelet serotonin-2 receptor binding sites in depression and suicide.

In order to examine the role of serotonin-2 (5HT2) receptors in depression and suicide, we determined 5HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the binding ligand in platelets obtained from 20 normal control and 23 drug-free depressed patients. Our results indicate significantly increased 125I-LSD binding sites (Bmax) in the platelets of depressed patients compared with normal control subjects. We also observed that a subgroup of depressed patients with a recent history of suicide attempts or suicidal ideation had significantly higher 5HT2 binding sites as compared with nonsuicidal depressed patients and normal controls. There were no significant differences in the apparent dissociation constant (Kd) values in the platelets of depressed patients compared with normal control subjects. To examine if the baseline 5HT2 receptors are related to either the severity of illness or treatment response, we determined the relationships of the baseline Bmax and Kd with baseline Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale (BPRS) scores and change in scores after treatment. We found no significant correlation between baseline Bmax and Kd with the baseline HDRS or BPRS scores or change in these scores after psychoactive drug treatment. These results thus indicate increased platelet 5HT2 receptors in depression, but much more so in depressed patients with suicidal ideation or attempts.

Adult↗
PubMed1990

Meta-analysis of value of propranolol in prevention of variceal haemorrhage.

A meta-analysis of all controlled clinical trials of beta-adrenoceptor blocking drugs, principally propranolol, in the prevention of primary or secondary variceal bleeding has shown that beta-blockade significantly reduced the occurrence of variceal bleeding, deaths from variceal bleeding, and overall mortality. There was some heterogeneity between trials in the effect of beta blockade on secondary prevention. When only fully reported, randomised, placebo-controlled studies were included the heterogeneity disappeared, and the reductions in bleeding episodes and mortality became more striking. Separate analyses of primary and secondary prevention studies also showed clear reductions in occurrence of variceal bleeding and deaths. These results seem to indicate the value of beta-adrenoreceptor blocking drugs for the primary prevention of haemorrhage from large oesophageal varices. However, there is still a need for large multicentre trials of beta-blockade for primary prevention of variceal bleeding in patients without large varices and of comparisons between beta-blocker therapy with other treatments in secondary prevention.

Adrenergic beta-Antagonists↗
PubMed1990

Unfolding intermediates in the triple helix to coil transition of bovine type XI collagen and human type V collagens alpha 1(2) alpha 2 and alpha 1 alpha 2 alpha 3.

The thermal triple helix to coil transitions of two human type V collagens (alpha 1(2) alpha 2 and alpha 1 alpha 2 alpha 3) and bovine type XI collagen differ from those of the interstitial collagens type I, II, and III by the presence of unfolding intermediates. The total transition enthalpy of these collagens is comparable to the transition enthalpy of the interstitial collagens with values of 17.9 kJ/mol tripeptide units for type XI collagen, 22.9 kJ/mol for type V (alpha 1(2) alpha 2), and 18.5 kJ/mol for type V (alpha 1 alpha 2 alpha 3). It is shown by optical rotatory dispersion and differential scanning calorimetry that complex transition curves with stable intermediates exist. Type XI collagen has two main transitions at 38.5 and 41.5 degrees C and a smaller transition at 40.1 degrees C. Type V (alpha 1(2) alpha 2) shows two main transitions at 38.2 and 42.9 degrees C and two smaller transitions at 40.1 and 41.3 degrees C. Compared to these two collagens type V (alpha 1 alpha 2 alpha 3) unfolds at a lower temperature with two main transitions at 36.4 and 38.1 degrees C and two minor transitions at 40.5 and 42.9 degrees C. The intermediates present at different temperatures are characterized by resistance to trypsin digestion, length measurements of the resistant fragments after rotary shadowing, and amino-terminal sequencing. One of the intermediate peptides has been identified as belonging to the alpha 2 type V chain, starting at position 430 and being about 380 residues long. (The residue numbering begins with the first residue of the first amino-terminal tripeptide unit of the main triple helix. The alpha 2(XI) chain was assumed to be the same length as the alpha 1(XI). One intermediate was identified from the alpha 2(XI) chain and with starting position at residue 495, and three from the alpha 3(XI) with starting positions at residues 519, 585, and 618.

Amino Acid Sequence↗
PubMed1990

Isolation and structural characterization of three isoforms of recombinant consensus alpha interferon.

Recombinant DNA-derived consensus alpha interferon was expressed in Escherichia coli and purified. Isoelectric focusing of this purified protein indicated the presence of three isoelectric subforms of pI 6.1, 6.0, and 5.7. These three subforms were preparatively separated by isoelectric focusing using Immobiline polyacrylamide gel and did not exhibit apparent differences in biological activity and tertiary structure. The pI 5.7 subform could also be separated from the pI 6.1 and 6.0 subforms by reverse-phase HPLC. Automated N-terminal amino acid sequence analysis of the pI 6.1 and 6.0 subforms yielded sequences corresponding to the methionyl and des-methionyl forms of the protein, respectively. Sequence analysis of the pI 5.7 subform indicated that its N terminus is blocked. To further determine the structure of the blocking moiety in the pI 5.7 subform, a blocked N-terminal tryptic peptide was isolated from HPLC peptide mapping of the S-carboxymethylated derivative. Results obtained from mass spectroscopic and amino acid analyses of this peptide suggest that it is blocked with an acetyl group at the N-terminal cysteine residue.

Amino Acid Sequence↗
PubMed1990

Clinical toxicity of cryopreserved bone marrow graft infusion.

We prospectively evaluated infusion-related toxicities in 82 recipients of autologous bone marrow grafts. The grafts were cryopreserved in 10% dimethylsulfoxide and stored in liquid nitrogen. All grafts were concentrated and buffy-coat cells were collected. Forty-seven grafts were treated ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 100 micrograms/mL; 26 grafts were further processed using density-gradient separation and treated with 4-HC at 60 micrograms/mL. Nine buffy-coat concentrates were frozen without drug treatment. Before infusion, patients were medicated with mannitol, hydrocortisone, and diphenhydramine. Grafts were rapidly thawed and immediately infused without further manipulation. During the infusions, 33 (70%) recipients of treated buffy-coat, 5 (56%) recipients of untreated buffy-coat, and 6 (23%) recipients of density-gradient separated grafts experienced varying symptoms including nausea, abdominal cramping, and flushing. Forced vital capacities for 83% of the recipients of treated buffy-coat concentrates decreased after the graft infusion; six of these patients complained of dyspnea and one patient experienced an acute episode of respiratory decompensation. Decreased heart rates were observed in 98% of the recipients of treated buffy-coat cells with asymptomatic bradycardia occurring in 45%. Forty-five patients (96%) in this group experienced transient hypertension, with 18 (38%) requiring additional medications within 6 hours after the infusion for control of blood pressure. Similar cardiovascular changes were observed in the recipients of untreated buffy-coat concentrates. One recipient of an untreated buffy-coat concentrate had 2 degrees heart block after the graft infusion. Twenty-three (88%) recipients of density-gradient separated grafts had decreased heart rates and 21 (81%) had increased blood pressure. However, the degrees of change were less than those experienced by the recipients of treated buffy-coat cells (P less than .01). Forced vital capacities were not affected by the infusion of the density-gradient separated grafts. No renal failure or obvious hemolytic episodes occurred for any patient group. Minor to moderate toxicities were associated with cryopreserved graft infusions. Recipients of buffy-coat separated grafts, both treated and untreated, experienced more complications than the recipients of density-gradient separated grafts. These toxicities may relate to the volumes of cryoprotectant and cell lysis products infused, which were less for the more highly purified density-gradient separated grafts.

Blood Chemical Analysis↗
PubMed1990

Precise quantitation of PAIgG: a new radiometric microtechnique.

We report the development of a radiometric assay for platelet-bound IgG that is both sensitive and quantitative. The assay utilized 96-well millititer plates incorporating a 0.2 microns filter membrane in the bottom. A 125I-labeled monoclonal antihuman IgG, as a secondary antibody, detected the platelet-bound human IgG. Since 5 x 10(6) platelets were used for each assay, tests for platelet-bound IgG can be performed on persons with severe thrombocytopenia. For the detection of circulating antiplatelet alloantibodies, as little as 10 microliters of platelet-free plasma per assay is required. Antiplatelet IgG was quantitated by using anti-PIA1 antibody that was purified with affinity and elution and DEAE chromatography. This purified antiplatelet antibody was labeled with 125I and was used to determine the binding ratio of secondary antibody to primary antibody. Under our standard conditions, this ratio was found to be stable at approximately 0.35 over the sensitivity range of the assay. The assay can detect approximately 200 molecules of human IgG per platelet (0.1 ng of secondary antibody bound per 5 x 10(6) platelets). It has a linear range from 0 to 7,000 molecules per platelet. Quantitation of anti-PIA1 binding for platelets stored for up to 6 months under refrigeration showed no change in number of PIA1 binding sites. Clinical studies showed that 18 of 19 ITP patients had an increased number of IgG molecules per platelet as did patients with malignancy and drug-induced immune thrombocytopenia. Patients who had received multiple platelet transfusions had antiplatelet antibody in their plasma. Normal amounts of PAIgG were observed in platelets and plasma of patients with nonimmune thrombocytopenia. The advantages of this method are that it is: 1) a more precise quantitation of PAIgG via direct measurement of binding ratio with PIA1 antibody; 2) performed with small amounts of platelets and plasma; 3) both sensitive and specific; and 4) reliably reproducible with both fresh and stored platelets.

Antibodies, Anti-Idiotypic↗
PubMed1990

Impaired chemotactic responses of bronchoalveolar leukocytes in experimental pneumoconiosis.

Rats were exposed to clouds of the following pneumoconiotic dusts: quartz, coal-mine dust, and chrysotile asbestos at 10 or 50 mg/m3 for 8, 32, and 75 days; for comparison, rats were also exposed to the non-pathogenic dust titanium dioxide (TiO2). The bronchoalveolar leukocytes (macrophages and neutrophils) from dust-exposed and control rats were obtained by lavage and tested for their ability to migrate toward zymosan-activated serum. Varying amounts of neutrophils were present depending on the ability of the dust to cause inflammation and the length of exposure. There was a marked loss of chemotactic ability in leukocytes from rats inhaling the pneumoconiotic dusts compared with controls; TiO2-exposed leukocytes had some impairment of chemotaxis, but this was substantially less than that found with the pneumoconiotic dusts. The loss of chemotactic activity did not correlate with the percentage of neutrophils in the lavage cells except when there were very high levels of neutrophils, and there was substantial impairment of chemotaxis with negligible numbers of neutrophils, showing that macrophage chemotaxis was impaired. A phagocytic burden within the leucocytes was not sufficient alone to inhibit chemotaxis, nor was the loss of chemotactic activity due to occupied receptors, since incubation failed to restore chemotaxis. Loss to chemotactic activity by leukocytes from pneumoconiotic dust-exposed lung could be an important factor in the development of pneumoconiosis.

Animals↗
PubMed1990

Drug therapy for bronchopulmonary dysplasia.

With improved survival of critically ill premature infants, BPD has become an important sequela of neonatal intensive care. A variety of medications are used in the management of BPD. In this article we have attempted to summarize clinical efficacy, pharmacokinetics, and side effects of many of these medications. Longer-term studies on the efficacy of drug therapy are needed and may be facilitated by the development of accurate and reproducible computerized techniques for the measurement of pulmonary mechanics in neonates. Ultimately, new pharmacologic agents or other strategies that will prevent lung injury from hyperoxia and mechanical ventilation or accelerate tissue repair once injury occurs will play a major role in the prevention and treatment of infants with BPD.

Bronchodilator Agents↗