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J J Miller

Publications and source records attributed to J J Miller.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fosphenytoin reduces hippocampal neuronal damage in rat following transient global ischemia.

Fosphenytoin, a water-soluble disodium phosphate ester of phenytoin, is a phenytoin prodrug with similar anticonvulsant properties. In this study, we evaluated its neuroprotective properties in a cardiac arrest-induced global ischemia model. After 12 minute ischemia, Long-Evans hooded rats were resuscitated, given fosphenytoin (30 mg/kg, i.m.) or saline 5 minutes after the ischemic episode, and killed on day 7. Brains were removed, fixed, and vibratome sectioned to assess the numbers of normal appearing CAI pyramidal neurons and for immunohistological staining of glial fibrillary acidic protein (GFAP). After global ischemia, the number of hippocampal CA1 pyramidal neurons decreased significantly (from 14.33 +/- 1.73 to 2.19 +/- 0.16 per 100 micron 2). Most hippocampal CA1 pyramidal neurons showed signs of injury and GFAP immunoreactivity of the region increased. With fosphenytoin treatment 5 min after ischemia, hippocampal CA1 pyramidal neurons remained at near control level (13.90 +/- 0.92), however, GFAP staining was not significantly changed. Our data, although indicating different neuronal and glial responses following fosphenytoin treatment, nevertheless, suggest that fosphenytoin is an effective neuroprotectant against ischemia-induced damage.

Analysis of Variance↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor induces activation and restores respiratory burst activity in monocytes from septic patients.

Monocyte activation in response to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was examined in vitro in septic shock patients. These monocytes exhibited a greater respiratory burst activity than monocytes from healthy subjects; the response to secondary stimulation with bacterial stimuli was attenuated. GM-CSF restored the ability of monocytes to respond appropriately to secondary stimulation. Expression of certain integrin adhesion molecules, L-selectin, and Fcgamma receptors was increased on monocytes of septic shock patients; expression of CD11c was reduced. GM-CSF up-regulated integrin expression and decreased L-selectin, FcgammaRII, and FcgammaRIII expression. Septic patients exhibited greater biologic activity of monocyte tissue factor than did healthy subjects. Priming monocytes with GM-CSF accelerated tissue factor activation following stimulation with lipopolysaccharide and bacterial culture supernatant. Certain parameters of monocyte function may be restored by exposure to GM-CSF. This benefit may be offset by an increase in monocyte procoagulant activity.

Adult↗
PubMed1997

Glia are the main source of lactate utilized by neurons for recovery of function posthypoxia.

Experiments are described in which a rat hippocampal slice preparation was used along with the metabolic glial inhibitor, fluorocitrate (FC), to investigate the role of glial-made lactate and its shuttling to neurons in posthypoxia recovery of synaptic function. After testing two less effective concentrations of FC, only 10.1 +/- 6.5% of slices treated with 100 microM of the metabolic toxin recovered synaptic function at the end of 10-min hypoxia and 30-min reoxygenation. In contrast, 79.6 +/- 7.4% of control, untreated slices recovered synaptic function after 10-min hypoxia and 30-min reoxygenation. The low rate of recovery of synaptic function posthypoxia in FC-treated slices occurred despite the abundance of glucose present in the medium before, during, and after hypoxia. The amount of lactate produced by FC-treated slices during the hypoxic period was only 62% of that produced by control, untreated slices. Supplementing FC-treated slices with exogenous lactate significantly increased the posthypoxia recovery rate of synaptic function. These results strongly support our previous findings concerning the mandatory role of lactate as an aerobic energy substrate for the recovery of synaptic function posthypoxia and clearly show that the bulk of the lactate needed for this recovery originates in glial cells.

Animals↗
PubMed1997

Brain lactate, not glucose, fuels the recovery of synaptic function from hypoxia upon reoxygenation: an in vitro study.

Lactate has been considered for many years to be a useless, and frequently, harmful end-product of anaerobic glycolysis. In the present in vitro study, lactate-supplied rat hippocampal slices showed a significantly higher degree of recovery of synaptic function after a short hypoxic period than slices supplied with an equicaloric amount of glucose. More importantly, all slices in which anaerobic lactate production was enhanced by pre-hypoxia glucose overload exhibited functional recovery after a prolonged hypoxia. An 80% recovery of synaptic function was observed even when glucose utilization was blocked with 2-deoxy-D-glucose during the later part of the hypoxic period and during reoxygenation. In contrast, slices in which anaerobic lactate production was blocked during the initial stages of hypoxia did not recover their synaptic function upon reoxygenation despite the abundance of glucose and the removal of 2-deoxy-D-glucose. Thus, for brain tissue to show functional recovery after prolonged period of hypoxia, the aerobic utilization of lactate as an energy substrate is mandatory.

Animals↗
PubMed1997

Brain lactate is an obligatory aerobic energy substrate for functional recovery after hypoxia: further in vitro validation.

This study used the rat hippocampal slice preparation and the monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), to assess the obligatory role that lactate plays in fueling the recovery of synaptic function after hypoxia upon reoxygenation. At a concentration of 500 microM, 4-CIN blocked lactate-supported synaptic function in hippocampal slices under normoxic conditions in 15 min. The inhibitor had no effect on glucose-supported synaptic function. Of control hippocampal slices exposed to 10-min hypoxia, 77.8 +/- 6.8% recovered synaptic function after 30-min reoxygenation. Of slices supplemented with 500 microM 4-CIN, only 15 +/- 10.9% recovered synaptic function despite the large amount of lactate formed during the hypoxic period and the abundance of glucose present before, during, and after hypoxia. These results indicate that 4-CIN, when present during hypoxia and reoxygenation, blocks lactate transport from astrocytes, where the bulk of anaerobic lactate is formed, to neurons, where lactate is being utilized aerobically to support recovery of function after hypoxia. These results unequivocally validate that brain lactate is an obligatory aerobic energy substrate for posthypoxia recovery of function.

Animals↗
PubMed1997

Hepatosplenic cat-scratch disease and abdominal pain.

BACKGROUND: There have been several recent reports that cat-scratch disease (CSD) causes a multiplicity of atypical clinical syndromes. We recently diagnosed hepatosplenic CSD in a child who was seen with fever and abdominal pain. We report this case and 10 other patients with hepatosplenic CSD and highlight the importance of abdominal pain in this clinical entity. METHODS: This was a retrospective review of charts of patients with a diagnosis of cat-scratch disease at Egleston Children's Hospital between January, 1985, and June, 1996. From these cases patients with hepatosplenic CSD were selected for study. RESULTS: Seven children (64%) had significant abdominal pain, and in three children abdominal pain was their chief complaint. All children in the study had pathologic evidence of CSD or elevated titers of antibodies to Bartonella henselae. Ultrasound examination showed that all children had microabscesses in the spleen, and eight had abscesses in the liver. CONCLUSIONS: One of the most remarkable findings in this large series of cases of hepatosplenic CSD was that 64% of the patients complained of abdominal pain. All children in this study received antibiotics. It was our clinical impression that once antibiotics had been started, the patients appeared to improve very quickly. With an increased index of suspicion, the use of B. henselae serology and an abdominal ultrasound examination, the diagnosis of this underrecognized disease might be more readily made.

Abdominal Pain↗
PubMed1997

Total clinical laboratory test volume in Connecticut, 1994-1995.

OBJECTIVE: To measure the volume of clinical laboratory testing in Connecticut during a one-year period. To explore the potential value of such data. DESIGN: Summary and analysis of federal and state clinical laboratory registration/licensure/inspection forms. SETTING: 2,333 clinical laboratory test facilities registered in Connecticut. MAIN OUTCOME MEASURES: The total clinical laboratory output for Connecticut by type of facility and category of technology over a 12-month period. RESULTS: During 1995, 2,333 registered clinical laboratory test facilities performed approximately 65,427,103 analyses in Connecticut. This represents approximately 20 tests per person per year. Thirty-five acute care hospitals performed 59.4%, nine large commercial laboratories 33.2%, 30 small commercial laboratories 1.7%, 1,491 physicians' offices 3.9%, and a miscellaneous group 1% of the tests. Test volumes are further segregated into eight major categories of technology: chemistry 59%, hematology 23.3%, microbiology 5.6%, blood banking 2.9%, coagulation 2.8%, waived tests 2.7%, urine analysis 1.8%, cytology 0.9%, and histology 0.8%. CONCLUSION: For the first time mechanisms are in place to measure essentially all clinical testing for a given area. With minor changes the data collection system could be greatly improved. The possible uses for such a data bank are discussed.

Clinical Laboratory Techniques↗
PubMed1996

Analytical performance of a monoclonal digoxin assay with increased specificity on the ACS:180.

Digoxin metabolites cross-react in the Ciba Corning ACS digoxin assay in proportion to their bioactivity, but have greater (near 100%) cross-reactivity in the Abbott TDx, Baxter Stratus, and Ciba Corning Magic RIA digoxin assays. We studied the analytical performance of the ACS digoxin assay and compared it with these other assays. Coefficients of variation ranged from 5.5% at 3.11 ng/ml to 8.8% at 0.57 ng/ml. Mean analytical recovery was 96.4%. Results on dilutions were linear in the range of 0.6-5.0 ng/ml. We observed no interference by hemoglobin, bilirubin, or triglycerides. Dihydrodigoxin and digitoxin had lower cross-reactivity in the ACS and Stratus assays than in the TDx and Magic assays. Digoxin-like immunoreactive factor (DLIF) in patients' sera was not detected in the ACS assay but was in the TDx, Stratus, and Magic assays. Digibind therapy seemingly did not affect digoxin results by ACS or Stratus, but did for up to 10 days after therapy for TDx and Magic. We compared digoxin results for 121 sera from 49 patients. Deming regression analysis was performed on the first specimen from each patient: ACS = 1.08(TDx)-0.17 ng/ml (r = 0.961, Sy,x = 0.164); ACS = 1.16(Stratus)-0.46 ng/ml (r = 0.973, Sy,x = 0.123); ACS = 1.00(Magic)-0.20 ng/ml (r = 0.982, Sy,x = 0.110). Discrepant results (> 2Sy,x from the regression line) were usually lower by the ACS assay (87%). Nine of 11 patients with discrepant results had renal insufficiency or hepatic disease, conditions commonly associated with increased DLIF. These observations may be explained by the improved specificity of the ACS digoxin assay.

Antibodies, Monoclonal↗
PubMed1996

Inaccuracy of three-finger pinch method of determining salt content in homemade sugar salt solutions.

Oral rehydration therapy (ORT) has dramatically reduced the morbidity and mortality associated with acute infectious diarrhea. Commercial oral rehydration salt (ORS) solutions with sodium concentrations of 30-90 mmol/L are ideal for both the prevention and treatment of dehydration. However, logistic issues impede their universal availability and homemade sugar salt (HSS) solutions are widely used in some areas of the world. The least accurate methods of preparing HSS solutions utilize a three-finger pinch of salt. The present study demonstrates the inconsistency and inaccuracy of this method among 15 health workers who participated in an ORT training seminar conducted in a situation that approximated field conditions. Similar studies with different subjects, instructions, and milieu describe results similar to those we obtained. In all studies, including the present one, a substantial number of the solutions prepared by this method had dangerously high or low sodium concentrations. Health providers should consider the use of selected home-available fluids rather than HSS solutions for the prevention of dehydration in children with diarrhea. However, ORS solutions should be used to correct established dehydration.

Adult↗
PubMed1996

Migrating monopredominant arthritis in children of Assyrian ancestry.

We describe an unusual form of arthritis affecting 3 Assyrian children to inspire a search for further cases to determine how unique it may be. After different patterns of onset, 3 of 4 children with arthritis from the Assyrian community in northern California had an unusual course of recurrent arthritis, predominantly in one joint at a time. There was rapid cartilage and bone destruction in involved joints. The 3 children are HLA-DR4. The 4th patient had a more typical childhood polyarticular course. Two of the first 3 patients had fever with attacks. None had rheumatoid factor, antinuclear antibody, or the HLA-B27 antigen. This unusual, severe, monopredominant but migrating arthritis appears to be particularly associated with Assyrian descent.

Adolescent↗
PubMed1996

Anti-lipid A antibodies in childhood arthritis: methods of immobilization affect quantitation and crossreactivity measured by ELISA.

OBJECTIVE: To find an optimal method to study antibodies reactive with monophosphoryl lipid A characteristic of oligoarticular arthritis in children. METHODS: ELISA using 3 different methods of immobilization were compared, in (1) HCO3 buffer, pH 9.6; (2) HCl, pH 2.0; and (3) methanol. Competitive inhibition studies were carried out to quantitate relative avidity of cross reactions with suspected autoantigens. RESULTS: Sera from healthy children reacted significantly more strongly with monophosphoryl lipid A after immobilization in acid or in methanol than in a basic buffer. Sera from children with oligoarticular arthritis reacted more strongly than normal sera with the basic buffer method and even more strongly with the methanol method, but were not distinguishable from normal sera with the acid method. Results with individual oligoarticular sera correlated from method to method, but results with normal sera did not. Collagen types I and II, cardiolipin, and denatured DNA can block the anti-monophosphoryl lipid A reactivity to varying degrees on plates prepared with basic buffer, but only collagen type I and DNA block reactivity on plates prepared with methanol. CONCLUSION: The epitope on monophosphoryl lipid A recognized by oligoarticular sera is differentially affected by the method of immobilization. The crossreactivity of the anti-monophosphoryl lipid A antibody in this disease is confirmed.

Antibodies↗
PubMed1996

VH4-34 (VH4.21) gene expression in the chronic arthritides of childhood: studies of associations with anti-lipid A antibodies, HLA antigens, and clinical features.

OBJECTIVE: To determine if the germ line gene VH4-34 (VH4.21) encodes the antimonophosphoryl lipid A (MPL) polyspecific antibodies found in oligoarticular arthritis of childhood. METHODS: Sera from a range of rheumatic diseases of childhood were assayed for VH4-34 derived antibodies by ELISA using the antiidiotype monoclonal antibody 9G4. Results were compared to assays for anti-MPL antibodies, C4d, and Bb, and for HLA type, joint count, and sedimentation rate. RESULTS: VH4-34 derived antibodies were elevated in all diseases studied except rheumatoid factor positive polyarticular disease. In oligoarticular arthritis, VH4-34 gene expression correlated with C4d concentration, and VH4-34 encoded globulins were more concentrated in synovial fluid than in blood. No association was found with HLA type. An association between VH4-34 expression and IgG anti-MPL was found in sera from patients from Cincinnati but not from Stanford. No other evidence supported a direct association between VH4-34 derived and anti-MPL antibodies in these children. CONCLUSION: The expression of VH4-34 is increased in several rheumatic diseases of childhood, but, as in adults, not in rheumatoid arthritis. VH4-34 expression is not associated with HLA type. The polyspecific autoantibody nature of some VH4-34 derived antibodies may explain the wide range of the unusual antibodies found in oligoarticular arthritis.

Antibodies↗