Search PubMed⌕ Search

Biomedical subjects

D J Johnson

Publications and source records attributed to D J Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1997

A replicable and customizable approach to improve ambulatory care and research.

Health care is a service industry. A fundamental attribute of many successful service industries is the "small replicable unit (SRU)." There are three essential elements of an SRU: (1) the smallest core unit of activity, (2) micromeasures designed to help manage the core activities, and (3) combinations of the activities and measures to match local customer needs. In this article, we describe a model for geriatric care based on "SRU thinking." We demonstrate how this approach places measurement of patient values, clinical improvement strategies, and research objectives into day-to-day health care delivery.

Aged↗
PubMed1997

Treatment of liver injuries at level I and level II centers in a multi-institutional metropolitan trauma system. The Midwest Trauma Society Liver Trauma Study Group.

OBJECTIVE: The development of trauma systems and trauma centers has had a major impact on the fate of the critically injured patient. However, some have suggested that care may be compromised if too many trauma centers are designated for a given area. As of 1987, the state of Missouri had designated six adult trauma centers, two Level I and four Level II, for the metropolitan Kansas City, Mo, area, serving a population of approximately 1 million people. To determine whether care was comparable between the Level I and II centers, we conducted a concurrent evaluation of the fate of patients with a sentinel injury, hepatic trauma, over a 6-year period (1987-1992) who were treated at these six trauma centers. METHODS: All patients during the 6-year study period who suffered liver trauma and who survived long enough to be evaluated by computerized tomography or celiotomy were entered into the study. Patients with central nervous system trauma were excluded from analysis. Information concerning mechanism of injury, RTS, Injury Severity Score (ISS), presence of shock, liver injury scoring, mode of treatment, mortality, and length of stay were recorded on abstract forms for analysis. Care was evaluated by mortality, time to the operating room (OR), and intensive care unit (ICU) and hospital length of stay. RESULTS: Over the 6-year period 300 patients with non-central nervous system liver trauma were seen. Level I centers cared for 195 patients and Level II centers cared for 105. There was no difference in mean ISS or ISS > 25 between Level I and II centers. Fifty-five (28%) patients arrived in shock at Level I centers and 24 (23%) at Level II centers. Forty-eight patients (16%) died. Thirty-two (16%) died at Level I centers, and 16 (15%) died at Level II centers. Twenty of 55 patients (36%) in shock died at Level I centers, and 11 of 24 (46%) died at Level II centers (p = 0.428). Forty-three patients (22%) had liver scaling scores of IV-VI at Level I centers, and 10 (10%) had similar scores at Level II centers (p < 0.01). With liver scores IV-VI, 22 of 43 (51%) died at Level I centers and 10 of 14 (71%) died at Level II centers (p = 0.184). There was no difference in mean time or in delays beyond 1 hour to the OR for those patients in shock between Level I and II centers. There was a longer ICU stay at Level II centers (5.0 +/- 8.3 vs. 2.8 +/- 8.4 days, p = 0.04). This difference was confined to penetrating injuries. There was no difference in hospital length of stay. CONCLUSIONS: In a metropolitan trauma system, when Level I and II centers were compared for their ability to care for victims of hepatic trauma, there was no discernible difference in care rendered with respect to severity of injury, mortality, delays to the OR, or hospital length of stay. It was observed that more severe liver injuries were seen at Level I centers, but this did not seem to significantly affect care at Level II centers. There was a longer ICU stay observed at Level II centers owing to penetrating injuries, possibly because there were fewer penetrating injuries treated at these facilities. Although the bulk of patients were seen at Level I centers, care throughout the system was equivalent.

Adult↗
PubMed1996

Sex differences in the effectiveness of elaborative strategy use: knowledge access comparisons.

Dual-task procedures-elaborative strategy use and finger-tapping-were used to examine both recall and mental effort demands of elaboration strategy use with equal numbers of boys and girls at grades two and three. Knowledge-base access was examined by comparing different item types in the associative learning list: masculine, feminine, and mixed. Results showed that boys and girls did not differ in their recall of arbitrarily paired items (e.g., mixed pairs). A Sex by Item Type (masculine vs feminine) interaction, however, revealed that for feminine pairs girls recalled more than boys, whereas for masculine pairs no sex difference was observed. Finger tapping interference scores indexed mental effort. Similar to the recall findings, results indicated that the elaboration of feminine pairs required less mental effort by girls in contrast to boys. Elaboration of masculine pairs was not associated with a sex difference. The results were discussed in terms of sex differences in knowledge-base access.

Child↗
PubMed1995

Factor VIIa and the extracellular domains of human tissue factor form a compact complex: a study by X-ray and neutron solution scattering.

The four-domain structure of human factor VIIa and the two-domain structure of tissue factor form a tight complex to initiate blood coagulation. By solution scattering, the mean X-ray and neutron radii of gyration RG (which determine macro-molecular elongation) were found to be 3.25 nm, 2.13 nm and 3.14 nm (+/- 0.13 nm) for factor VIIa, the extracellular region of tissue factor and their complex in that order. The mean cross-sectional radii of gyration RXS were 1.33 nm, 0.56 nm and 1.42 nm (+/- 0.13 nm) in that order. The mean lengths were 10.3 nm, 7.7 nm and 10.2 nm in that order. The data show that, in solution, the free proteins have extended domain structures, and the complex is formed by a compact side-by-side alignment of the two proteins along their long axes. The high binding affinity of tissue factor for factor VIIa may thus be accounted for by the occurrence of many intermolecular contacts in the complex.

Animals↗
PubMed1995

Protein-bound pyrroles in rat hair following subchronic intraperitoneal injections of 2,5-hexanedione.

Studies were initiated to ascertain whether body hair could be used to develop a biological marker for chronic exposure to industrial neurotoxicants that yield the metabolite 2,5-hexanedione (2,5-HD), that is, n-hexane and methyl n-butyl ketone. Rats were injected daily with a 50 mg/kg ip dose of 2,5-HD for 45 d. At intervals, body hair and individual vibrissae were removed (under general anesthesia) and tested for the presence of pyrrole substances with p-N,N-dimethylaminobenzaldehyde (DMAB, Ehrlich's reagent). Vibrissae and body hair were stained a reddish color that was distinctly different from that observed with the hair taken from control animals. Solubilized body hair protein from the treated animals gave a positive Ehrlich's test, while that from control animals was negative. Spectral analysis of the DMAB-treated hair from experimental animals disclosed a maximum absorbance at 530 nm, which indicated the presence of pyrrole substituents. Serial analysis of individual nose hairs taken during 2,5-HD administration showed a progression with time of the region staining positively for pyrroles, thus indicating that the process can proceed in growing hair. These findings suggest the potential utility of hair as an indicator for chronic exposure to this class of industrial chemicals possessing neurotoxicity potential. This could complement urinary analysis, which is now used to confirm recent exposure.

Animals↗
PubMed1995

Characterization of mutations within the factor VIII gene of 73 unrelated mild and moderate haemophiliacs.

To screen for mutations within the factor VIII gene of 101 patients (85 unrelated), we used denaturing gradient gel electrophoresis (DGGE) after DNA amplification of target regions, including all coding regions except for the middle part (amino acid 757 to amino acid 1649) of the B domain. With this method, missense mutations were identified in 86% of unrelated patients. 41 different mutations were identified: 25 of them have not been described previously. Five of the genotypes are associated with CRM+ and 26 with CRMred status. Patients who are definitely related to each other showed no differences in DNA sequence. One patient showed two different base pair alterations, the first at amino acid 469 [ala(GCA-->gly(GGA)] and the second at position 473 [tyr(TAT)-->cys(TGT)]. One patient with an amino acid change at position 1689 [arg(CGC)-->his(CAC)] has developed an inhibitor against factor VIII.

Base Sequence↗
PubMed1995

Out-of-hospital ventilation: bag--valve device vs transport ventilator.

OBJECTIVE: To examine the patterns of out-of-hospital airway management and to compare the efficacy of bag-valve ventilation with that of the use of a transport ventilator for intubated patients. METHODS: A prospective, nonrandomized, convenience sample of 160 patients requiring airway management in the out-of-hospital urban setting was analyzed. A survey inquiring about airway and ventilatory management was completed by emergency medical services (EMS) personnel, and arterial blood gas (ABG) samples were obtained within 5 minutes of patient arrival in the ED. The ABG parameters were compared for patients grouped by different airway techniques and presence or absence of cardiac arrest (systolic blood pressure < 50 mm Hg) upon ED presentation. RESULTS: Over a one-year period, 160 surveys were returned. The majority (62%) of the patients were men; the population mean age was 61 +/- 19 years. Presenting ABGs were obtained for 76 patients; 17% (13/76) had systemic perfusion and 83% (63/76) were in cardiac arrest. There was no difference in ABG parameters between the intubated cardiac arrest patients ventilated with a transport ventilator (pH 7.17 +/- 0.17, PaCO2 37 +/- 20 torr, and PaO2 257 +/- 142 torr) and those ventilated with a bag-valve device (pH 7.20 +/- 0.16, PaCO2 42 +/- 21 torr, and PaO2 217 +/- 138 torr). The patients ventilated via an esophageal obturator airway (EOA) device had impaired gas exchange, compared with the groups who had endotracheal (ET) intubation (pH 7.09 +/- 0.13, PaCO2 76 +/- 30 torr, and PaO2 75 +/- 35 torr). The intubated patients not in cardiac arrest had similar ABG parameters whether ventilated manually with a bag-valve device or with a transport ventilator. Endotracheal intubation was successfully accomplished in 93% (123/132) of attempted cases. CONCLUSIONS: In this sample, ET intubation was the most frequently used airway by EMS providers. When ET intubation was accomplished, adequate ventilation could be achieved using either bag-valve ventilation or a transport ventilator. Ventilation via the EOA proved inadequate.

Adult↗
PubMed1995

Decreased elastin synthesis in normal development and in long-term aortic organ and cell cultures is related to rapid and selective destabilization of mRNA for elastin.

We have previously shown that aortic organ cultures from 1- to 3-day-old chickens initially mimic the high levels of elastin production seen in vivo. However, more prolonged incubation of these tissues results in decreased synthesis of elastin. In the present study, we demonstrate that decreased production of elastin in these aortic organ cultures is selective for elastin compared with collagen and is correlated with decreased steady state levels of mRNA for elastin. These decreases in steady state levels of elastin mRNA are due at least in part to a rapid and selective destabilization of mRNA for elastin, the half-life of which falls from approximately 25 hours in fresh aortic tissues to approximately 15 hours after incubation for only 8 hours. Destabilization of elastin mRNA can be prevented by incubation in the presence of blockers of DNA transcription (5,6-dichlorobenzimidazole riboside and actinomycin D) and mRNA translation (cycloheximide). Furthermore, the half-life of aortic elastin mRNA decreases from approximately 25 hours in the 1-day-old chicken to approximately 7 hours in the 8-week-old chicken, demonstrating that destabilization of mRNA is an important contributing factor in the decline in production of aortic elastin taking place during normal postnatal growth.

Age Factors↗
PubMed1995

An overview of learning disabilities: psychoeducational perspectives.

In general, people with learning disabilities are a heterogeneous population that require a multidisciplinary evaluation and careful, well-planned intervention. Despite this heterogeneity, patterns of problems often co-occur. Therefore, diagnosticians and educators should look beyond single areas of achievement such as reading or arithmetic. In addition, problems in one area of learning typically have secondary impacts on higher levels of learning. That is, comprehension problems typically interfere with expression. Every effort should be made to examine patterns of problems and to avoid fragmentation of services so that each area of underachievement is not treated separately. Although learning disabilities usually interfere with school performance, they are not simply academic handicaps. They interfere with certain social activities as well as occupational pursuits. In many instances, they impact on mental health and self-esteem. Therefore, students need multiple services. And, as emphasized throughout this journal issue, learning disabled individuals may have comorbid conditions such as attention deficit disorder, depression, and neurologic problems. Furthermore, the problems may change over time. Children may first be identified because of language comprehension problems but later have reading or mathematics difficulty. With intervention, oral expressive problems may be alleviated but may be manifested later in written language.

Child↗
PubMed1994

Surface plasmon resonance studies of the interaction between factor VII and tissue factor. Demonstration of defective tissue factor binding in a variant FVII molecule (FVII-R79Q).

The blood coagulation cascade is initiated when vessel injury allows factor VII (FVII) to form a complex with tissue factor (TF). Complete deficiency of FVII causes a lethal bleeding diathesis, but individuals with moderately reduced FVII levels are often asymptomatic. Some of these individuals have circulating partially functional FVII, as a result of point missense mutations in critical parts of the molecule. One such mutation has been reported at position 79 in the first epidermal growth factor-like (EGF) domain of FVII, where an arginine residue has been replaced by glutamine. There is controversy as to whether or not this mutation reduces the affinity of the FVII/TF interaction compared to wild-type FVII. To address this problem, we have expressed recombinant FVII-R79Q and subjected it to detailed biochemical analysis. One-stage FVII:C assays show the variant FVII to have reduced activity with respect to the wild type. Rates of autoactivation and activation by FXa to the two-chain molecule were identical for wild-type and variant FVII. The Vmax for FX activation was lower for the mutant as measured using an amidolytic assay for FX activity. In contrast, the Km for FX was lower for the variant than the wild-type molecule. Peptidyl substrate hydrolysis was virtually identical for both variant and normal FVIIa in the presence and absence of TF. The variant has reduced affinity for TF as measured by surface plasmon resonance. FVII-R79Q has an association rate constant (kassoc) one-fifth of that of normal FVII, but a similar kdiss, resulting in a decrease in the affinity of the enzyme for its cofactor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A pilot study of patient quality of life during radiation therapy treatment.

The purpose of this research was to develop a quality of life (QOL) tool that would help to reveal any physical, mental or emotional changes patients may experience while receiving radiation therapy. Research focusing on quality of life during radiation therapy is in its infancy. Although many tools to measure QOL have been developed, until very recently few had been geared specifically toward those receiving radiation therapy. In addition to a radiation-specific instrument, the goal was to develop a multidimensional measure that would be short in length and could be completed by the patient in 15 min or less. This new Quality of Life Radiation Therapy Instrument (QOL-RTI) is a visual analogue scale with 24 questions and is not site specific. Twenty-one patients with various diagnoses and treatment sites completed the questionnaire at baseline and then weekly during the course of radiation therapy. The internal consistency of the instrument (Cronbach's alpha) was 0.87. At baseline each patient also was asked to complete the Ferran's and Powers QLI Cancer Version 6 (QLIC); the correlation between the QLIC and the QOL-RTI was 0.47. These results are based on a small number of patients, but initial efforts in creating an instrument that is quick and easy for patients to complete have been encouraging. An additional 70-80 patients are now being entered into a study using the QOL-RTI to further evaluate reliability and validity.

Female↗
PubMed1994

Comparison of pressure and flow triggering systems during continuous positive airway pressure.

STUDY OBJECTIVE: Compare the inspiratory work of breathing (WOBI) during pressure triggering (PT), and flow triggering (FT) using two microprocessor ventilators. DESIGN: A randomized, crossover comparison of triggering strategies and ventilators used. SETTING: Surgical intensive care unit. PATIENTS: Ten patients recovering from acute respiratory failure (eight men, two women; mean age, 48 +/- 12 years) breathing on continuous positive airway pressure (CPAP) of 5 cm H2O were studied. INTERVENTIONS: Patients were randomly assigned to either receive 5 cm H2O CPAP via one of two units (Hamilton Veolar or Puritan Bennett 7200ae) using either PT or FT. Each patient had 30-min trials using the following: (1) Veolar FT; (2) Veolar PT; (3) 7200ae FT; and (4) 7200ae FT. MEASUREMENTS AND RESULTS: During each trial period, work of breathing (WOB) and pressure time product (PTP) were measured using a respiratory monitor (Bi-core CP-100). All patients were placed in semi-Fowler position and esophageal balloons were inserted and their position confirmed using the occlusion technique. Continuous measurements of peak negative pressure during inspiration, tidal volume (VT), minute ventilation (VE), respiratory frequency (f) were accomplished with a flow transducer at the proximal airway. FT with the 7200ae was superior to PT as measured by both the WOB (0.58 +/- 0.3 vs 0.84 +/- 0.2 J/L, p < 0.01) and PTP (148 +/- 50 vs 206 +/- 41 cm H2O/s/min, p, 0.05). FT with the Veolar was also superior to PT with respect to the WOB (0.53 +/- 0.2 vs 0.93 +/- 0.2 J/L, p < 0.01) and PTP (140 +/- 39 vs 229 +/- 46 cm H2O/s/min, p < 0.05). CONCLUSION: FT reduces the WOB compared with PT, regardless of the ventilator used. The reduction in WOB during FT is related to improved responsiveness and changes in the posttrigger phase.

Cross-Over Studies↗
PubMed1994

Factor VIII S373L: mutation at P1' site confers thrombin cleavage resistance, causing mild haemophilia A.

A novel CRM+ mutation, factor VIII position 373 serine to leucine substitution (FVIII 373-Leu) was identified during a survey of Factor VIII (FVIII) mutations. We have purified the variant protein from the patient's plasma in order to allow further characterisation of the molecule. The CRM+ plasma contained 120% Factor VIII antigen (FVIII:Ag) and 6% Factor VIII coagulant activity (FVIII:C). After purification the mutant FVIII was subjected to thrombin proteolysis, and was thereby activated 5.6-fold compared with 7-fold for wild type molecule. Subsequently, spontaneous inactivation of the mutant was much slower than noted for wild type FVIII. Western blot analysis using monoclonal antibodies demonstrated that thrombin cleavage of FVIII 373-Leu at positions 740 and 1689 were normal but that cleavage at position 372 was completely absent. Crystallographic coordinates of the active site of thrombin complexed to fibrinopeptide A were used to explore possible mechanistic reasons for the failure of thrombin to cleave the mutant FVIII at position 372. Steric hindrance between the mutant side chain and the side chain of the P1 residue was apparent. We conclude that the functional defect of FVIII 373-Leu results from the inability of thrombin to cleave the mutant at position 372-373, and propose that this is due to steric hindrance by the side chain of leucine 373, preventing correct formation of the enzyme substrate complex.

Antibodies, Monoclonal↗
PubMed1993

Double heterozygosity for mutations in the platelet glycoprotein IX gene in three siblings with Bernard-Soulier syndrome.

Bernard-Soulier syndrome (BSS) giant platelets have defective and/or deficient glycoprotein (GP) Ib/IX complexes, causing absent ristocetin-induced aggregation, defective interaction with von Willebrand factor, morphologic abnormality, and a clinical bleeding tendency. Recently several mutations have been described in the platelet GPIb alpha gene in individuals exhibiting the BSS phenotype. We have studied a family with classical BSS, and have excluded lesions at the GPIb alpha locus by restriction fragment length polymorphism linkage analysis. Analysis of the genes for two other components of the platelet GPIb:IX complex, namely GPIb beta and GPIX, showed two different missense mutations in the coding region of the GPIX gene: an A-->G transition in codon 21 results in conversion of an aspartic acid to glycine and an A-->G change in codon 45 converts an asparagine residue to serine. Three affected individuals are doubly heterozygous for these mutations, which alter conserved residues in or flanking the GPIX leucine-rich glycoprotein motif. Both mutations create new recognition sites for the enzyme Fnu 4H1; therefore, this enzyme was used to screen 60 normal subjects (120 alleles). Neither mutation was detected in any subject other than direct relatives of the affected individuals. Although low levels of GPIb were demonstrable by both flow cytometry and immunoblot analysis in an affected individual's platelets, there was no evidence of GPIX immunoreactivity. We propose that expression of abnormal GPIX prevents stable assembly of the GPIb/IX complex, causing BSS in the doubly heterozygous individuals in this family.

Amino Acid Sequence↗
PubMed1993

Airway pressure release ventilation.

BACKGROUND: Elevated airway pressures during mechanical ventilation are associated with hemodynamic compromise and pulmonary barotrauma. We studied the cardiopulmonary effects of a pressure-limited mode of ventilation (airway pressure release ventilation) in patients with the adult respiratory distress syndrome. METHODS: Fifteen patients requiring intermittent mandatory ventilation (IMV) and positive end-expiratory pressure (PEEP) were studied. Following measurement of hemodynamic and ventilatory data, all patients were placed on airway pressure release ventilation (APRV). Cardiorespiratory measurements were repeated after a 2-hour stabilization period. RESULTS: During ventilatory support with APRV, peak inspiratory pressure (62 +/- 10 vs 30 +/- 4 cm H2O) and PEEP (11 +/- 4 vs 7 +/- 2 cm H2O) were reduced compared with IMV. Mean airway pressure was higher with APRV (18 +/- 5 vs 24 +/- 4 cm H2O). There were no statistically significant differences in gas exchange or hemodynamic variables. Both cardiac output (8.7 +/- 1.8 vs 8.4 +/- 2.0 L/min) and partial pressure of oxygen in arterial blood (79 +/- 9 vs 86 +/- 11 mm Hg) were essentially unchanged. CONCLUSIONS: Our results suggest that while airway pressure release ventilation can provide similar oxygenation and ventilation at lower peak and end-expiratory pressures, this offers no hemodynamic advantages.

Adult↗
PubMed1993

Continuous duodenal feeding restores gut blood flow and increases gut oxygen utilization during PEEP ventilation for lung injury.

Positive end-expiratory pressure (PEEP) improves oxygenation but, at moderate levels, limits portal blood flow (PBF) and may cause relative splanchnic ischemia. Under these conditions, methods of supporting gut physiology may prevent the sequelae of gut ischemic damage. Enteral feeding is known to cause splanchnic hyperemia in uninjured animals. In order to study the effects of continuous enteral feeding on gut hemodynamics in a flow-limited environment, six dogs underwent the insertion of arterial, pulmonary artery, and portal and hepatic vein catheters. Splenectomy and duodenostomy were performed, and the hepatic artery and portal vein were encircled with flow probes. Lung injury (LI) was undertaken with intravenous oleic acid (0.08 mL/kg), followed by incremental additions of PEEP totaling 10 cm H2O to correct shunt. Continuous elemental feeding (1 kcal/mL, 3 mL/kg/hr) was started through the duodenostomy. Cardiac index (CI), PBF, and gut oxygen delivery and consumption (GO2D, GO2C) were measured at baseline (T0), 1 hour after LI and PEEP (T1), and 1 hour after drip feeding was begun (T2). Lung injury and PEEP significantly decreased CI, PBF, and GO2D without changing GO2C. Feeding returned PBF and GO2D to baseline levels without changing CI. GO2C increased significantly compared with baseline levels. Based on prior studies, these changes do not represent recovery of the injured model. Continuous enteral feeding, therefore, redistributed CI to the portal circulation. The improved gut hemodynamics documented in this model may preserve splanchnic integrity and prevent gut-derived complications.

Animals↗