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Biomedical subjects

J P Mitchell

Publications and source records attributed to J P Mitchell.

At least 19 recordsLinked to original sources
PubMed2005

Agricultural dust production in standard and conservation tillage systems in the San Joaquin Valley.

The negative health effects of repeated dust exposure have been well documented. In California's San Joaquin Valley, agricultural operations may contribute substantially to airborne particulates. We evaluated four management systems to assess impacts on dust production and soil properties for a cotton (Gossypium hirsutum L.)-tomato (Lycopersicon esculentum Mill.) rotation: standard tillage with (STCC) and without (STNO) cover crop, and conservation tillage with (CTCC) and without (CTNO) cover crop. Gravimetric analysis of total dust (TD, <100-mum aerodynamic diameter) and respirable dust (RD, 4-mum aerodynamic diameter) samples collected in the plume generated by field implements showed that dust concentrations for CTNO treatments were about one-third of their STNO counterparts for both cumulative TD and RD measured throughout the two-year rotation, primarily due to fewer in-field operations. The TD and RD production for STNO and STCC was comparable, whereas the CTCC system produced about twice as much TD and RD as CTNO. Energy dispersive spectroscopy (EDS) analyses showed absolute increases of 8 and 39% organic fragments in STCC and CTCC over STNO and CTNO, respectively, while organic fragments in the TD increased by 6% in both cover crop treatments. Soil C content was positively correlated with clay content and increased by an average of 0.12 and 0.07% in the cover crop and non-cover crop treatments, respectively, although soil C for each treatment showed a distinct response to a field texture gradient. While dust emissions show an immediate decrease due to fewer field operations for the conservation tillage treatments, long-term sampling is necessary to determine the effects that increased aggregation through organic matter additions may have on dust production.

Agriculture↗
PubMed2004

Hydrofluoroalkane-beclomethasone versus chlorofluorocarbon-beclomethasone delivery in neonatal models.

Dose delivery of hydrofluoroalkane-beclomethasone and chlorofluorocarbon-beclomethasone was compared during in vitro neonatal simulations: mechanical ventilation with 40% and 100% relative humidity + Neonatal Chamber-Ventilator System/endotracheal tube; manual ventilation + Neonatal Chamber/endotracheal tube; "spontaneous breathing" + Neonatal Chamber/face mask without/with manual assistance. The delivery of hydrofluoroalkane-beclomethasone was significantly greater in each simulation.

Administration, Inhalation↗
PubMed2003

Prevalence of T cell receptor zeta chain deficiency in systemic lupus erythematosus.

T cells from patients with systemic lupus erythematosus (SLE) display antigen receptor-mediated signaling aberrations associated with defective T cell receptor (TCR) zeta chain expression. We determined the prevalence of TCR zeta chain deficiency in SLE from a large cohort of unselected racially diverse patients with different levels of clinical disease activity as determined by SLE Disease Activity Index (SLEDAI). Our data show that the occurrence of TCR zeta chain deficiency is 78% in SLE patients. There was no relationship between the deficiency of TCR zeta chain and the SLEDAI scores or theapy. TCR zeta chain deficiency was also not associated with age, race or gender and persisted over a 3 year follow-up period. Thus, there is a high prevalence of TCR zeta chain deficiency in SLE patients that is independent of disease activity, and persists over time indicating an important role for TCR zeta chain deficiency in SLE pathogenesis.

Adult↗
PubMed2002

Engagement of complement receptor 2 on the surface of B cells from patients with systemic lupus erythematosus contributes to the increased responsiveness to antigen stimulation.

B cells from patients with systemic lupus erythematosus (SLE) display increased responses following cross-linking of the surface antigen receptor. We explored the possibility that the increased responses are at least partially due to simultaneous cross-linking of the complement receptor 2 (CR2). To this end, we stimulated fresh B cells from SLE patients with an anti-IgD antibody conjugated to the Epstein-Barr virus gp350 protein, which binds to CR2, and recorded the free intracytoplasmic calcium response during the first 10 min. Despite the fact that SLE B cells were found to express half as many surface CR2 as normal B cells, both peak responses and the percentage of responding cells were significantly increased in the former. These observations suggest that regulatory molecules such as CR2 are involved in the increased B cell responses in SLE patients. We propose that certain immune complexes that circulate in the sera of SLE patients that have anti-surface immunoglobulin specificities and are decorated with natural ligands of CR2, such as C3d, elicit and promote B cell overactivity.

Adult↗
PubMed2002

Does inflammatory proteolytic activity contribute to the increased factor IX activation peptide in men at high risk of coronary heart disease? A preliminary study.

In the Second Northwick Park Heart Study, the activation peptides of factor IX (FIXpep) and factor X (FXpep) were measured in 1261 middle-aged men by double-antibody radioimmunoassay. During follow-up 147 men who had a first coronary heart disease (CHD) event were found to have had an increased FIXpep (p = 0.003) and a reduced FXpep (p = 0.05) at baseline compared with those remaining CHD-free (controls). Plasma FIXpep and FXpep were positively associated, but the rate of rise in FIXpep with increasing FXpep was higher in cases than controls (p for interaction = 0.01). In a sample of 87 controls, FIXpep was positively and independently related to the concentrations of a polymorphonuclear-specific fibrinogen degradation product (p = 0.036) and FXpep (p = 0.004), but in larger samples no statistically significant associations were found either with C-reactive protein or with fibrinogen concentration. The findings suggested that the increased FIXpep in men at high CHD-risk may have been partly due to the generation of factor IX inactivation peptides by inflammatory proteolysis and their recognition together with true FIXpep in the radioimmunoassay. Direct evidence for this hypothesis requires development of assays for human elastase-specific factor IX inactivation peptides.

Case-Control Studies↗
PubMed2001

Defective FcgammaRIIb1 signaling contributes to enhanced calcium response in B cells from patients with systemic lupus erythematosus.

B lymphocytes from patients with systemic lupus erythematosus (SLE) display enhanced B cell antigen receptor (BCR)-mediated early signal transduction events, including increased fluxes of intracytoplasmic calcium ([Ca(2+)](i)). Because crosslinking of FcgammaRIIb1 (CD32) in normal B cells suppresses the BCR-initiated signal transduction process, we investigated whether the increased BCR-initiated [Ca(2+)](i) response in SLE B cells is the consequence of decreased FcgammaRIIb1-mediated suppression. To this end, we used flow cytometry to study the [Ca(2+)](i) responses of indo-1-loaded negatively gated B cells stimulated with F(ab')(2) fragments or whole IgG anti-human micro Ab. We found that the ratio of F(ab')(2) to whole anti-micro Ab [Ca(2+)](i) response was significantly lower in SLE B cells compared to B cells from patients with other systemic rheumatic diseases or normal individuals (P < 0.01). Because the surface expressions of FcgammaRIIb1 and surface IgM were similar in B cells from SLE patients and disease and normal controls, these data indicate a decrease in FcgammaRIIb-mediated suppression in SLE B cells. In addition, the whole IgG anti-micro Ab but not its F(ab')(2) fragment caused increased redistribution of SH2 domain-containing inositol 5'phosphatase in SLE compared to normal and disease control B cells. In conclusion, deficient FcgammaRIIb1-mediated suppression contributes to the augmented [Ca(2+)](i) responses of human SLE B cells.

Adult↗
PubMed2001

Juvenile dermatomyositis presenting with anasarca: A possible indicator of severe disease activity.

Juvenile dermatomyositis is a rare autoimmune disease characterized by inflammation of the muscle, skin, and other organs. Although localized edema is a common feature of juvenile dermatomyositis, generalized edema has been reported infrequently. We describe a patient with juvenile dermatomyositis presenting with anasarca and note that generalized edema has been associated with severe disease activity.

Child↗
PubMed2000

Comparison of novel hemostatic factors and conventional risk factors for prediction of coronary heart disease.

BACKGROUND: This study sought to assess whether novel markers of hemostatic activity are predictive of coronary heart disease (CHD) and improve risk assessment. METHODS AND RESULTS: Conventional CHD risk factors, the activation peptides of factor IX and factor X, factor VII activity and antigen, activated factor XII, prothrombin fragment 1+2, fibrinopeptide A, and fibrinogen were measured in 1153 men aged 50 to 61 years who were free of myocardial infarction at recruitment. Activated factor VII (VIIa) was measured in 829 men. During 7.8 years of follow-up, 104 had a CHD event. Baseline status was related to outcome by logistic regression by using a modified nested case-control design. Screening performance was judged from receiver operating characteristic curves. A high activated factor XII was associated with increased CHD risk, but low levels were not protective. Plasma VIIa and factor X activation peptide were independently and inversely related to risk. Plasma factor IX activation peptide and fibrinogen were positively associated with risk, but the relations were no longer statistically significant after adjustment for other factors, including VIIa and apoA-I. Other hemostatic markers were not associated with CHD risk. CONCLUSIONS: Hemostatic status did not add significant predictive power to that provided by conventional CHD risk factors yet was able to substitute effectively for these factors.

Biomarkers↗
PubMed2000

Now you see it, now you don't: explicit versus implicit measures of the personal/group discrimination discrepancy.

When making explicit self-report ratings, members of status- and racial-minority groups report less personal experience with discrimination than that encountered by their group--a phenomenon called the personal/group discrimination discrepancy (PGDD). This study provides evidence, for the first time, that the PGDD may be, in part, a product of the procedure used to measure it. White women and men completed explicit and implicit measures of personal and group discrimination based on sex. The PGDD surfaced among women in the explicit measures, but not in the implicit measures. These findings suggest that explicit and implicit measures might provide different assessments of experience with discrimination.

Adult↗
PubMed2000

Guideline implementation in the department of defense.

To improve the effectiveness of evidence-based clinical practice guidelines (CPGs), four other components of implementation are necessary. Together, they impressively optimize the process and outcomes of health care, and reduce undesirable variation of care. Aside from CPGs, the four components help make up a successful, long-term, facility-wide, comprehensive disease-management program. First, executive clinical and administrative leaders need to create the expectation and reveal hands-on commitment. Second, work-simplification tools are needed to accomplish the tasks more effectively and to encourage a path of least resistance. Third, useful, accurate metrics are needed to provide feedback for patients and health-care providers who need the most assistance. These metrics must be easily obtained, disseminated in near-real time, patient-specific, anonymous to others, and penalty free. Fourth, and most important, with nonmonetary compensation, this review addresses the question, "What's in it for all the passionate people who assist in the delivery of health care?"

Asthma↗
PubMed1999

A direct method for the formation of peptide and carbohydrate dendrimers.

Two new methods for the modification of PAMAM dendrimers have been developed which allow the covergent synthesis of either peptide or carbohydrate-bearing dendrimer molecules. Both methods involve condensation between hydroxylamino nucleophiles and appropriate carbonyl-bearing reaction partners.

Carbohydrates↗
PubMed1999

Time-of-flight aerodynamic particle size analyzers: their use and limitations for the evaluation of medical aerosols.

Time-of-flight (TOF) aerosol analyzers are a class of instruments that measure the aerodynamic diameter of individual particles following a controlled acceleration in a well-defined flow field. Two instruments have been used to analyze the size of medical aerosols: Aerosizer particle size analyzer (TSI Particle Instruments/Amherst, Amherst, MA), Aerodynamic Particle Sizer (APS) aerosol spectrometer (TSI) Both instruments are capable of sizing several thousand particles a second, making it possible to obtain aerodynamic particle size distributions in a few seconds compared with up to 1 hour per measurement using compendial methods that are based on either the multistage liquid impinger or cascade impactor. This rapidity makes TOF analysis attractive for product development, as many different variables can potentially be investigated during a short period of time. The data thus obtained should be used with caution, however. Several issues, most notably the lack of a direct relationship with the mass of drug substance present and the vulnerability of the measurements to coincidence effects when sampling concentrated aerosols, may severely limit the value of data from many aerosol delivery systems, especially pressurized metered dose inhalers (pMDIs). A review of the literature illustrating the issues that are involved and providing guidance on the most appropriate uses of these analyzers is presented.

Aerosols↗
PubMed1999

Size analysis of a pressurized metered dose inhaler-delivered suspension formulation by the API Aerosizer time-of-flight aerodynamic particle size analyzer.

Aerosizer time-of-flight (TOF) aerodynamic particle size analyzers (TSI-Amherst, Amherst, MA) are widely used for the rapid assessment of aerosols from a wide variety of drug delivery devices, including pressurized metered dose inhalers (pMDIs). This technique offers significant advantages in terms of rapid measurement times in comparison with the more time-consuming compendial methods such as the cascade impactor or multistage liquid impinger. Particle size analysis takes place by determining the TOF of individual particles following acceleration to supersonic velocity. No drug assay is performed; thus, the resulting size distribution also includes particles that do not contain any medication such as the excipients and surfactant that are present in most pMDI-based formulations. Illustrative data are presented for one particular formulation (Pulmicort: 200 micrograms of budesonide per dose; Astra Draco; Lund, Sweden) and demonstrate that bias from this source can significantly shift the reported particle distribution to finer sizes compared with impactor-based analysis in which direct assay for drug has taken place. In this case, the mass median aerodynamic diameter (MMAD) determined by an Aerosizer-LD was close to 2.4 microns, but was found to be approximately 4 microns using the cascade impactor-based procedure. Such a shift results in an overestimation of the fine particle fraction of the emitted dose, which may lead to misleading conclusions about the therapeutic benefit of a particular drug delivery system when making use of this formulation. TOF aerosol measurement techniques appear to be vulnerable to this type of bias for any suspension formulation in which the drug content is not homogeneously distributed within all particle sizes.

Bronchodilator Agents↗
PubMed1997

In vitro performance testing of three small volume-holding chambers under conditions that correspond with use by infants and small children.

The in vitro behavior of three types of small volume-holding chambers intended for use by infants and small children (child AeroChamber, Vent-170 and Space Chamber) has been compared with two pMDI-delivered aerosol formulations (salbutamol: 100 micrograms unit dose and beclomethasone di-propionate (BDP): 50 micrograms unit dose) widely prescribed for this age group of patients. All devices were evaluated using a pediatric breathing simulator that created respiratory conditions likely to be encountered with infants and small children. The filter that collected aerosol delivered from the holding chamber on test was located at approximately the position that the patient's lips would be in the mask, by means of an annular support plate glued into the mask itself. At the lowest tidal volume (50 ml), no salbutamol or BDP was delivered by either the Vent-170 or Space Chamber, whereas the unit doses from the child AeroChamber were 39.7 +/- 1.6 micrograms and 11.8 +/- 1.2 micrograms, respectively. The Vent-170 and Space Chamber delivered measurable doses of both drugs when the tidal volume was increased to 100 ml and again to 200 ml, however, the corresponding doses available from the AeroChamber were always significantly greater. These findings emphasize the importance of designing in vitro tests that mimic use by the patient group for which the device is intended. In vitro measurements made at constant high flow rates in excess of 20 l/min do not reveal these differences in performance that are clinically significant, and may lead the physician to prescribe a device that under certain conditions may not deliver any drug to infants or small children.

Aerosols↗
PubMed1997

Risk of coronary heart disease and activation of factor XII in middle-aged men.

Increased activity is known to be present in the extrinsic, intrinsic, and final common pathways of the hemostatic system in men at high risk of coronary heart disease (CHD), but the status of the contact system of coagulation in this condition is uncertain. Plasma levels of activated factor XII (XIIa), the initial product of contact activation, have therefore been measured by ELISA in 2464 men aged 51 to 62 years, clinically free of CHD, who were taking part in a prospective cardiovascular survey based in general medical practices. Statistically significant, independent, and positive associations of XIIa were found with serum cholesterol and triglyceride concentrations, blood pressure, body mass index, factor VII activity, plasma fibrinogen concentration, and tobacco smoking, all associated with CHD. Plasma XIIa also increased with recent alcohol intake. Men in the highest quintile of risk according to their conventional risk factors had a mean XIIa of 2.07 ng/mL (95% confidence interval 1.99-2.16), 31% higher than that of men in the lowest quintile (1.58; 95% confidence interval 1.51-1.65). Thus, the contact system of coagulation appears to be activated when CHD risk is increased. Furthermore, the independent associations of XIIa with the major conventional CHD risk factors and its broad range of values in the general population (0.1 to 12.5 ng/mL), combined with a relatively low day-to-day variability in individuals (the within-person component of its total variation being 14.7%), suggest its potential usefulness as a marker of atherosclerotic vascular damage.

Coronary Disease↗