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Biomedical subjects

J Hunt

Publications and source records attributed to J Hunt.

At least 37 records · Page 2Linked to original sources
PubMed2001

Determination of acrylamide and glycidamide in rat plasma by reversed-phase high performance liquid chromatography.

Acrylamide is a widely used monomer that produces peripheral neuropathy. It is metabolized to the epoxide, glycidamide, which is also considered to be neurotoxic. A new reversed-phase high-performance liquid chromatography (HPLC) method is described that permits simultaneous determination of acrylamide and glycidamide in rat plasma. Samples were deproteinized with acetonitrile and chromatography was performed using isocratic elution and UV absorption detection. The limits of detection for acrylamide and glycidamide were 0.05 and 0.25 microg/ml in plasma, respectively, and recovery of both analytes was greater than 90%. The assay was linear from 0.1 to 100 microg/ml for acrylamide and from 0.5 to 100 microg/ml for glycidamide. Variation over the range of the standard curve was less than 15%. The method was used to determine the concentration-time profiles of acrylamide and glycidamide in the plasma of acrylamide-treated rats.

Acrylamide↗
PubMed2001

S-nitrosoglutathione increases cystic fibrosis transmembrane regulator maturation.

Endogenous S-nitrosoglutathione (GSNO) is known to increase the expression of certain proteins at concentrations present in the normal human airway. We hypothesized that GSNO would increase expression and maturation of the cystic fibrosis transmembrane conductance regulator (CFTR). Cells expressing DeltaF508 and wild type CFTR were exposed to GSNO and analyzed for expression and maturation by Western blot analysis. Physiologically relevant concentrations of GSNO resulted in dose- and time-dependent increases in expression. The GSNO-induced increases were eliminated by cycloheximide, suggesting a posttranscriptional effect. Unlike proteasome inhibitors, GSNO resulted in an increase CFTR maturation. The GSNO effect could be reversed by dithiothreitol and inhibited by acivicin, a gamma glutamyl transpeptidase inhibitor. These observations suggest that GSNO leads to maturation of mutated DeltaF508 CFTR, a process associated with restoration of CFTR function. Because endogenous levels of GSNO are low in the cystic fibrosis (CF) airway, these results raise the possibility that GSNO replacement therapy could be an effective treatment for CF.

Animals↗
PubMed2001

Effects of cyclosporin A administered into the airways against antigen-induced airway inflammation and hyperreactivity in the rat.

The immunosuppressant cyclosporin A given orally has anti-asthma properties but carries an undesirable risk of systemic effects. We administered cyclosporin A to Brown Norway rats either orally (p.o.) or topically by intratracheal (i.t.) instillation into the airways before inhaled antigen. Cyclosporin A suppressed the antigen-induced accumulation of activated (CD25+) CD4+ T lymphocytes and eosinophils in the lung, interleukin-5 mRNA expression in lung tissue and airway hyperreactivity. Intratracheal cyclosporin A suppressed cell accumulation at a 10-fold lower dose than that required orally. Minimum effective doses were 3 mg x kg(-1) i.t. and 30 mg x kg(-1) p.o. Intratracheal administration reduced the plasma concentration and systemic exposure compared with an equieffective oral dose, but the reduction (4-5-fold) was not as large as anticipated. Our data suggests that although topical administration to asthmatics would provide some potential for an improved safety margin, it may not offer any major advantage over existing oral therapy. However, the data clearly demonstrate that a novel immunosuppressant with similar anti-inflammatory properties but reduced potential for systemic effects would offer an attractive therapy for severe asthma.

Administration, Inhalation↗
PubMed2001

Inhibition of calcium-stimulated ATPase in the hen brain P2 synaptosomal fraction by organophosphorus esters: relevance to delayed neuropathy.

Organophosphorus (OP) compounds have been reported to inhibit Ca/Mg-ATPase, but the relevance of this inhibition to organophosphate-induced delayed neuropathy (OPIDN) has not been explored. To determine if inhibition of this enzyme was related to the development of OPIDN, neuropathic and nonneuropathic OP compounds were sted for their ability to inhibit Ca-stimulated ATPase activity in the P2 synaptosomal fraction from hen brain. Following in vitro exposure to 10(-3) to 10(-5) M OP compounds, Ca-stimulated ATPase activity was inhibited by chlorpyrifos, chlorpyrifos-oxon, phenyl saligenin phosphate (PSP), and tri-o-tolyl phosphate (TOTP), but not by parathion, paraoxon, or diisopropyl fluorophosphate (DFP). Further investigation of inhibition induced by chlorpyrifos determined that inhibition was noncompetitive with respect to calcium and ATP. OP compound hydrophobicity was well correlated with in vitro inhibition of Ca-stimulated ATPase, suggesting that OP compounds interact with membrane lipids, and this interaction may contribute to the noncompetitive inhibition of Ca-stimulated ATPase that was observed. Subsequent to in vivo exposure, DFP, but not PSP, produced inhibition of Ca-stimulated ATPase activity in the hen brain P2 synaptosomal fraction. These data indicate that inhibition of Ca-stimulated ATPase activity is not correlated to neuropathic potential and demonstrate that inhibition of Ca/Mg-ATPase is not responsible for OPIDN.

Analysis of Variance↗
PubMed2001

Population-based incidence of pertussis among adolescents and adults, Minnesota, 1995-1996.

To estimate the incidence of pertussis, a prospective study was done among members of a managed care organization in Minneapolis/St. Paul, Minnesota. Of 212 patients 10-49 years old enrolled from January 1995 through December 1996, 8 were found to be culture positive, 10 were found to be positive by polymerase chain reaction assay, 13 had a > or =2-fold increase in IgG or IgA to pertussis toxin (PT), and 18 had IgG to PT in a single serum specimen > or =3 SD above the mean of an age-matched control group. At least 1 positive laboratory test result for pertussis infection was found in 27 (13%) patients, among whom the duration of cough illness was a median of 42 days (range, 27-66 days). On the basis of any positive laboratory result, the estimated annual incidence of pertussis was 507 cases per 100,000 person-years (95% confidence interval, 307-706 cases). Bordetella pertussis infection may be a more common cause of cough illness among adolescents and adults than was recognized previously.

Adolescent↗
PubMed2001

Angiomatosis of bone and soft tissue: a spectrum of disease from diffuse lymphangiomatosis to vanishing bone disease in young patients.

The application of cross-sectional imaging in the investigation of patients with angiomatosis reveals that lymphangiomatosis and vanishing bone disease should not be considered as separate entities, but rather as a spectrum of disease. We present a pictorial review of eight patients demonstrating the manifestations of soft tissue and bony involvement. We highlight a subgroup of patients with chyloid pleural effusions who have a poor prognosis.

Adolescent↗
PubMed2001

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: influence of immunosuppressive regimens.

Post-orthotopic liver transplantation (OLT) recurrence of hepatitis C is virtually universal, but histological progression of disease is not. This study examines long-term clinical and liver histological features at and after OLT to elucidate factors predictive of hepatitis C recurrence and progression after OLT. A blinded retrospective review of clinical, serological, and histopathologic features of 65 patients who underwent OLT for hepatitis C and Non A Non B hepatitis was conducted. Histological findings of recurrent hepatitis C and progression (fibrosis, >or= grade 2 by last follow-up) were correlated with clinical parameters. Histological recurrence of hepatitis C was seen in 43 of 65 patients, with progression in 19 patients. Histological findings in the native liver and post-OLT biopsy specimen at the time of recurrence showed no correlation with hepatitis C recurrence and progression. Patients treated with azathioprine (AZA)-containing immunosuppressive regimens experienced less recurrence (6 of 17 v 37 of 48 patients; P < .005) and progression (1 of 17 v 18 of 48 patients; P = .014) than those without AZA as part of their immunosuppressive regimen. No difference was seen between patients treated with cyclosporine versus those administered FK506 (P > .05). Histological recurrence of hepatitis C after OLT is seen in 66% of patients with progressive disease and 29% of all patients. The grade of inflammation in the native liver at the time of OLT and time of recurrence is not predictive of progression. AZA-containing regimens reduce histological recurrence and progression of hepatitis C in post-OLT patients.

Adolescent↗
PubMed2001

Anatomy, histologic features, and vascularity of the adult acetabular labrum.

Acetabular labrum tears have been implicated as a cause of hip pain in adult patients. Few studies describe the anatomy, histologic features, and microvasculature of the acetabular labrum and labral tears. Fifty-five embalmed and 12 fresh-frozen adult hips with a mean age of 78 years (range, 61-98 years) were studied. Of these, 96 % (53 of 55) of the hips had labral tears, with 74% of the tears located in the anterosuperior quadrant. Histologically, the fibrocartilaginous labrum was contiguous with the acetabular articular cartilage through a 1- to 2-mm zone of transition. A consistent projection of bone extends from the bony acetabulum into the substance of the labrum that is attached via a zone of calcified cartilage with a well-defined tidemark. Two distinct types of tears of the labrum were identified histologically. The first consisted of a detachment of the fibrocartilaginous labrum from the articular hyaline cartilage at the transition zone. The second consisted of one or more cleavage planes of variable depth within the substance of the labrum. Both types of labral tears were associated with increased microvessel formation seen within the tear. The acetabular labrum tear appears to be an acquired condition that is highly prevalent in aging adult hips. Labral tears occur early in the arthritic process of the hip and may be one of the causes of degenerative hip disease.

Acetabulum↗
PubMed2001

Abnormal CD40 ligand (CD154) expression in human immunodeficiency virus-infected children.

The CD40 ligand (CD154), expressed primarily on activated CD4-positive T cells, is a costimulatory molecule involved in B-cell proliferation, germinal center formation, and immunoglobulin class switching. Since B-cell abnormalities including hypergammaglobulinemia and abnormal antibody-specific immune responses are prominent and occur early during the course of pediatric human immunodeficiency virus (HIV) infection, we measured the baseline levels and the induced levels of expression of CD154 on CD3(+) CD8(-) (T helper cells) in HIV-infected children and uninfected children born to HIV-positive mothers. The percentage of CD154(+) T helper cells activated in vitro and the level of CD154 expressed per T helper cell (mean fluorescent channel [MFC]) were significantly lower in the HIV-infected children than in the uninfected control group (77% +/- 3% versus 89% +/- 1%, respectively [P < 0.002], and 261 +/- 174 versus 415 +/- 130 MFC, respectively [P < 0.03]). The levels of CD154 expressed on resting T helper cells in the HIV-infected group were not significantly different from the levels observed in the control group. In the HIV-infected children, the level of CD154 on activated T helper cells correlated with the level of immunodeficiency, as assessed by the CD4 T-cell levels (correlation coefficient [r] = 0.707, P = 0.003), but did not correlate with the viral load or with any of the serum immunoglobulin concentrations measured in this group of HIV-infected children. The baseline level of CD154 expressed on T helper cells did, however, correlate with the concentration of immunoglobulin A in serum. We conclude that HIV-infected children have impaired regulation of CD154 expression which may contribute to the immune dysregulation commonly observed.

Antibodies, Viral↗
PubMed2001

Salvage surgery.

Salvage surgery is an essential method in the armamentarium of the surgeon caring for the severely injured patient. The patient in unstable condition with multiple abdominal injuries is a challenge, even to the most experienced trauma surgeon. The first priority should be to control major vascular injuries and other sources of bleeding that are immediately life-threatening. Often after massive blood loss, the deadly triad of hypothermia, acidosis, and coagulopathy is present. Additional time in the operating room often worsens these physiologic parameters and patient outcome. Once surgically correctable bleeding has been addressed, such patients are best served by cessation of the operation, packing of the abdomen, and transfer to the intensive care unit. Resuscitative steps should then be taken. Once the physiologic derangement has been corrected, the patient can undergo definitive operative procedures.

Abdominal Injuries↗
PubMed2001

Use of an electronic medical record in disease management programs: a case study in hyperlipidemia.

Disease management programs seek to improve the health of a population of patients with a disease through a multidisciplinary approach founded in the collection, analysis and feedback of disease-specific outcomes. Currently, the majority of disease management programs have been conducted by insurers or external vendors. Limitations of these programs derive from separation of care from primary care and the inability to rapidly and accurately obtain the necessary clinical data. The utility offered by an electronic medical record allows physician organizations to conduct disease management programs of higher quality at lower cost.

Coronary Disease↗
PubMed2000

Senescent jejunal mast cells and eosinophils in the mouse preferentially translocate to the spleen and draining lymph node, respectively, during the recovery phase of helminth infection.

Because mice infected with Trichinella spiralis experience a pronounced, but transient, mastocytosis and eosinophilia in their intestine, this disease model was used to follow the fate of senescent T cell-dependent mast cells (MCs) and eosinophils. Very few MCs or eosinophils undergoing apoptosis were found in the jejunum during the resolution phase of the infection, even though apoptotic MCs were common in the large intestine. Although the mesenteric draining lymph nodes contained large numbers of apoptotic eosinophils, MCs were rarely found at this location. During the recovery phase, large numbers of MCs were present in the spleen, and many of these cells possessed segmented nuclei. These splenic MCs were not proliferating. Although MCs from the jejunum and spleen of noninfected mice failed to express mouse MC protease (mMCP) 9, essentially all of the MCs in the jejunal submucosa and spleen of T. spiralis-infected mice expressed this serine protease during the recovery phase. The MCs in the jejunum expressed mMCP-9 before any mMCP-9-containing cells could be detected in the spleen. The fact that mMCP-9-containing MCs were detected in splenic blood vessels as these cells began to disappear from the jejunum supports the view that many jejunal MCs translocate to the spleen during the recovery phase of the infection. During this translocation process, some senescent jejunal MCs undergo nuclear segmentation. These studies reveal for the first time different exit and disposal pathways for T cell-dependent eosinophils and MCs after their expansion in the jejunum during a helminth infection.

Animals↗
PubMed2000

An artificial immune system for data analysis.

We present a simplified view of those parts of the human immune system which can be used to provide the basis for a data analysis tool. The motivation for and reasoning behind such a model is given and the desire for a 'transparent' model and meaningful visualization and interpretation techniques is noted. A minimalist formulation of an artificial immune system and some of its behaviour is described. A simple implementation and a suitable visualization technique are demonstrated using some trivial data and the famous 'iris' data set.

Antibody Formation↗
PubMed2000

Relative activity and referral patterns for diabetes and non-diabetes in general practice.

AIMS: To describe and compare general practice (GP) activity for patients with and without diabetes using a survey of general practices representing over 10% of the Welsh population. METHODS: The Welsh GP Morbidity Database Project (GPMDP) collected data including demographic and lifestyle information and consultation data such as diagnosis, referral and surgical procedures. These data were analysed to establish the annual period prevalence of diabetes and compare the relative number of consultations and referrals. RESULTS: A total of 4,182 diabetic patients were recorded (prevalence 1.41%) and accounted for 77,371 (4.4%) consultations. Patients with diabetes were four-times more likely to be referred to community services (relative risk (RR) 4.1, 95% CI 3.7-4.7), in particular district nursing (RR 3.8, 1.9-7.7), optician services (RR 8.9, 5.0-15.7), chiropody (RR 8.2 6.4-10.5) and dietician services (RR 21.2, 17.6-25.5). Patients with diabetes were also more likely to be followed-up in general practice (RR 6.7, 6.2-7.2) both within 1 month (RR 6.7, 6.2-7.2) and 1 month to 1 year (RR 9.7, 8.9-10.7). Emergency admissions were also more likely for patients with diabetes (RR 6.8, 6.2-7.5) as were elective admissions to general medicine (RR 5.6, 4.6-6.7), surgery (RR 1.8, 1.5-2.0) and opthalmology (4.2, 3.4-5.2). CONCLUSION: The increased utilization of health services apparent in secondary care was confirmed in primary care. Further research is required to determine levels of community activity after initial referral.

Adolescent↗