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Biomedical subjects

J A Clark

Publications and source records attributed to J A Clark.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effect of amino acid infusion on glucose production in trauma patients.

The relationship between precursor supply and hepatic glucose output (HGO) was examined in 8 control subjects and 12 trauma patients after a fasting period of approximately 60 hours. Glucose kinetics were measured with a primed-constant infusion of [U-14C]glucose and [6-3H]glucose. The basal rate of HGO was 5.45 +/- 0.22 micromol x kg-1 x min-1 in the controls and 13.16 +/- 0.76 micromol x kg-1 x min-1 following trauma (p < 0.001). Four hours after amino acid infusion of 1.3 g x kg-1 x 24 h-1, HGO in the controls was unchanged at 5.35 +/- 0.22 micromol x kg-1 x min-1 but it had decreased to 11.71 +/- 0.67 micromol x kg-1 after trauma (p < 0.001). We conclude that increasing the supply of gluconeogenic precursors does not stimulate HGO in normal subjects after fasting or after severe trauma and that factors other than to availability of amino acids are responsible for the enhanced rate of HGO in trauma patients.

Adult↗
PubMed1996

Effect of lipid peroxidation inhibition on retinal ganglion cell death.

PURPOSE: To determine whether the lipid peroxidation inhibitor tirilazad mesylate can block the death of retinal ganglion cells induced by the inhibition of oxidative phosphorylation and glycolysis. METHODS: Rat retinal ganglion cells were labeled retrogradely with the fluorescent tracer DiI, and mixed cultures were prepared. Cell death was induced with chemical hypoxia, hypoglycemia, or glycolysis inhibition, and the effect on cell survival of tirilazad mesylate was assessed. RESULTS: Tirilazad mesylate enhanced relative ganglion cell survival after plating, with detectable effects at 200 nM and a maximal increase above diluent control of 148% +/- 2% at 20 microM. Relative survival at 24 hours in the presence of the complex IV inhibitor sodium cyanide (3 mM) was significantly greater when it was co-incubated with tirilazad mesylate than with diluent control (91.8% +/- 4.6% versus 39.3% +/- 7.1%; P = 0.008). Enhanced relative survival with tirilazad mesylate also was seen in cultures containing reduced glucose media. CONCLUSIONS: The lipid peroxidation blocker tirilazad mesylate inhibits retinal ganglion cell death in vitro. Because irreversible loss of retinal ganglion cells is the final common pathway in a variety of optic neuropathies, this or similar agents may be useful in animal models of optic neuropathies.

Animals↗
PubMed1996

Role of radiation therapy in retroperitoneal sarcomas.

Historically, patients with retroperitoneal sarcomas have had a poor prognosis. Surgical resection continues to be the standard treatment for these tumors. However, their anatomic location and large size at presentation often make complete surgical resection infeasible. Even with complete gross removal of tumor, most patients will experience local failure. Adjuvant radiation therapy has been used to improve local control rates. In the postoperative setting, radiation doses to the tumor bed are limited by radiation tolerances of surrounding normal tissues. Extrapolation of data from soft-tissue sarcomas at other sites suggests that delivery of higher radiation doses, in combination with surgery, may favorably affect local control. Preoperative radiation therapy, in combination with brachytherapy or intraoperative radiation therapy at the time of surgical resection, allows for the safe delivery of higher doses of radiation than is possible in the postoperative setting. These approaches make it possible to maximize the likelihood of local control and cure while minimizing normal tissue toxicity.

Antineoplastic Agents↗
PubMed1995

Unraveling the mystery: clues to systemic vasculitic disorders.

In this article, the author reviews some of the most common vasculitic disorders, including: polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Henoch-Schonlein purpura, giant cell arteritis, and Takayasu's arteritis. Information about the definition, general considerations, clinical findings, diagnostic tests, classification criteria, and treatment is included. The significance of early recognition of these disorders in the critical care area is discussed.

Critical Care↗
PubMed1995

Coagulase-negative staphylococci in multiple blood cultures: strain relatedness and determinants of same-strain bacteremia.

The frequency of strain relatedness was determined among randomly selected patients with coagulase-negative staphylococcal infections as determined in multiple blood cultures by plasmid typing, determination of species, and antibiotyping. Strain relatedness was demonstrated in 21 of 47 episodes of bacteremia (44.7%) among 34 patients, with a similar percentage among patients with two or one positive blood culture in 24 h (14 of 30 [46.7%] versus 7 of 17 [41.2%], respectively). Same-strain bacteremia was more frequent in cases of infection among patients with a corresponding fever (15 of 21 [71.4%]), among patients infected with organisms from an identifiable source (7 of 9 [77.8%]) and with non-Staphylococcus epidermidis species (9 of 11 [81.8%]), and among patients with nosocomially acquired infections (18 of 36 [50%]). Comparing episodes with or without strain relatedness, no difference was noted in the time to growth (2.1 +/- 1.4 versus 1.9 +/- 0.9 days, respectively), in bacterial growth in two culture bottles (5 of 14 [35.7%] versus 8 of 24 [33.3%], respectively), and in the presence of additional negative blood cultures (9 of 21 [42.9%] versus 11 of 26 [42.3%], respectively). The antibiotypes of all related strains and 7 of 44 (15.9%) unrelated pairs were identical. These findings demonstrate that coagulase-negative staphylococci from multiple blood cultures are frequently unrelated, suggesting a high prevalence of contamination. In the absence of precise measures for demonstrating strain relatedness, the combination of a clinical assessment with antibiotype determination appears to be a suitable alternative.

Adolescent↗
PubMed1995

Relevance of culturing Candida species from intravascular catheters.

The significance of isolating Candida species from intravascular catheters was examined retrospectively. Our findings demonstrate that these organisms are encountered among patients with proven invasive candidiasis or as an isolated finding. Febrile patients with yeasts in two or more additional sites may be at risk for invasive cadidiasis and may benefit from treatment.

Adolescent↗
PubMed1994

Cytokine production and aging: overproduction of IL-8 in elderly males in response to lipopolysaccharide.

Interleukin-8 (IL-8) is a chemoattractant cytokine for polymorphonuclear neutrophils, and is found at the site of inflammation and infection. The levels of IL-8 from an elderly (ages 65-79) and young (ages 20-27) population were compared. Secretion of IL-8 was measured in monocyte conditioned medium (MCM), under both a spontaneous condition and with stimulation with detoxified LPS (10 mg/ml). Spontaneous production of IL-8 in the elderly group (39.4 +/- 8.3 ng/ml, n = 16) was found to be significantly lower than the control group (66.4 +/- 5.0 ng/ml, n = 17), P < 0.01. A sex difference was observed within the elderly population, with the male elderly producing 8.8 +/- 2.1 ng/ml of IL-8 and the elderly females producing levels of 57.8 +/- 9.1 ng/ml. There was a good correlation between IL-8 and IL-1 production in the elderly but differences between the elderly and young production of IL-1 did not reach statistical significance. IL-8 and TNF production did not correlate. Upon stimulation with the LPS, the male elderly levels increased eightfold (70.1 +/- 11.8 ng/ml) and was significantly different from the young male level, P < 0.01, while the female elderly showed no change with stimulation. No sex difference was observed in the control population. These results indicate that the spontaneous secretion of IL-8 in elderly males is lower than that of both elderly females and the young control group. However, upon stimulation with LPS, the elderly males are capable of an overproduction of IL-8 when compared to the young group and the elderly females. This overproduction may be the result of an in vivo priming in this healthy elderly group. The female elderly followed a pattern similar to the young group, showing no change upon stimulation with the detoxified LPS. Sex differences related to the immune system have been noted in the past with females having a more active immune system, and these results may be related to this difference.

Adult↗
PubMed1994

A collaborative system of care for youth with severe emotional disturbances: an evaluation of client characteristics and services.

The closing of a state children's psychiatric hospital resulted in the mandated development of a regional children's mental health system for youths with severe emotional disturbances. The purpose of this article is to describe the demographic profiles and service usage patterns of youths enrolled in this system (Project youths) compared with random samples of non-Project youths involved with the mental health system. Data were obtained from two existing statewide databases (508K and MHIS). The 508K database revealed that Project youths (n = 393) were significantly older, had more severe functional impairments, more out of home placements, lower functional abilities, and were ill longer than non-Project youths (n = 747). Using the MHIS database, service usage patterns were assessed over time, across groups, and across the six local mental health authorities (LMHAs). Project youths (n = 266) received more case management, emergency, day treatment, and inpatient services than did non-Project youths (n = 262) and there were significant increases in case management and residential services over time. Differences among the LMHAs were found in all service types. Findings from this study indicated that Project youths were the most severely disturbed in the mental health system and received the most services. This study demonstrates the usefulness of analyzing existing statewide data in evaluating mental health systems.

Adolescent↗
PubMed1994

Small bowel biopsy through an enteroclysis catheter to augment findings at enteroclysis and hypotonic duodenography.

Proximal jejunal mucosal biopsy was performed by a radiologist through the nasojejunal catheter at the time of enteroclysis. Seventeen patients (10 men and seven women, aged 23-73 years [mean, 46 years]) were studied with enteroclysis because of clinical signs of malabsorption with suspected small bowel disease. In seven (41%) patients, results at biopsy were positive, and results in another seven (41%) were positive at enteroclysis. In 10 (59%) patients, results were positive at one or both tests. Performance of both small bowel biopsy and enteroclysis at the same session is feasible and offers additional clinically pertinent information than can be obtained at enteroclysis alone.

Barium Sulfate↗
PubMed1994

Stable expression of a neuronal gamma-aminobutyric acid transporter, GAT-3, in mammalian cells demonstrates unique pharmacological properties and ion dependence.

The transport proteins that mediate gamma-aminobutyric acid (GABA) reuptake have been major targets for the development of agents to treat neurological diseases such as epilepsy, where augmentation of GABAergic function is indicated. The recent isolation of cDNAs for four distinct brain GABA carriers has provided an avenue for creating more specific and selective antagonists of GABA transport. An LLC-PK1 cell line stably expressing GABA transporter type 3 (GAT-3), a beta-alanine-sensitive neuronal GABA transporter, has been generated and used to examine the kinetics, ion dependence, and pharmacological properties of the transporter. In this cell line, the GAT-3 carrier transports GABA with an apparent Km of 4 microM and a Vmax of 1.25 x 10(-16) mol/cell/min. beta-Alanine is a relatively potent inhibitor of GAT-3 GABA transport, with a K(i) value of 34 microM. beta-Alanine also serves as a substrate for the carrier (Km = 29 microM, Vmax = 1.82 x 10(-16) mol/cell/min) and appears to interact with the transporter at the same or a similar site as GABA. Other experimental GABA transport antagonists developed as anticonvulsant agents, including tiagabine, Cl-966, SKF-100330-A, SKF-89976-A, and NO-711, are weak inhibitors of GAT-3 GABA transport, suggesting that their therapeutic effects may be more related to their ability to block GABA transporters other than GAT-3. GAT-3 exhibits a sigmoidal dependence on Na+ concentration, with a Hill coefficient of 1.65, suggesting that more than one Na+ ion is involved in the transport mechanism. In contrast, the transport activity shows a hyperbolic Cl- dependence, with a Hill coefficient of 1.05. The Km for Cl- is 78 mM, a value severalfold higher than has been noted for another cloned GABA carrier, GABA transporter type 1. Interestingly, for GAT-3 a reduction of the Cl- concentration results in a small but consistent increase in the apparent Km for GABA, suggesting that the interaction of chloride with the transporter may be an important initial event in the mechanism of transport. These results underscore the unique properties of GAT-3 and distinguish this transporter as a new target for the development of GABA-mimetic agents.

Animals↗
PubMed1993

Amino acid neurotransmitter transporters: structure, function, and molecular diversity.

Many biologically active compounds including neurotransmitters, metabolic precursors, and certain drugs are accumulated intracellularly by transporters that are coupled to the transmembrane Na+ gradient. Amino acid neurotransmitter transporters play a key role in the regulation of extracellular amino acid concentrations and termination of neurotransmission in the CNS section. Transporters for the major amino acid neurotransmitters glutamate, GABA, and glycine are found in both neurons and glial cells. Recent work has resulted in the identification of cDNAs encoding several amino acid neurotransmitter transport proteins, all of which belong to the Na(+)- and Cl(-)-dependent transporter gene family. The diversity of this family suggests a degree of transporter heterogeneity that is greater than that indicated by biochemical and pharmacological studies.

Amino Acid Sequence↗
PubMed1993

A cutaneous lesion in a patient with AIDS: an unusual presentation of infection due to Mycobacterium avium complex.

A patient with AIDS developed a purplish, necrotic skin lesion followed by fevers, constitutional symptoms, and watery diarrhea. Stains of samples from the skin lesion and of stool and bone marrow revealed acid-fast bacilli, and Mycobacterium avium was isolated from cultures of these specimens and blood. With the initiation of multiagent oral antimycobacterial therapy, the patient's symptoms abated and the cutaneous lesion reepithelialized. We believe this lesion to be a manifestation of disseminated infection due to Mycobacterium avium complex (MAC). As the population of patients with AIDS who have CD4 cell counts of < 100/mm3 increases, new and unusual manifestations of disseminated MAC infection can be expected. New oral agents with increased activity against MAC may make early recognition and treatment of MAC infections more rewarding.

AIDS-Related Opportunistic Infections↗
PubMed1993

Evaluation of commercial presence-absence test kits for detection of total coliforms, Escherichia coli, and other indicator bacteria.

Evaluations of several commercial presence-absence (P-A) test kits were performed over a 6-month period in 1990 by using the Ontario Ministry of the Environment (MOE) P-A test for comparison. The general principles of the multiple-tube fermentation technique formed the basis for conducting the product evaluations. Each week, a surface water sample was diluted and inoculated into 25 99-ml dilution blanks for each of three dilutions. The inoculated dilution blanks from each dilution series were randomly sorted into sets of five. Three of these sets were inoculated into the P-A test kits or vice versa, as required. The other two sets were passed through membrane filters, and one set of five membrane filters was placed onto m-Endo agar LES to give replicate total coliform counts and the other set was placed onto m-TEC agar to give replicate fecal coliform results. A statistical analysis of the results was performed by a modified logistic transform method, which provided an improved way to compare binary data obtained from the different test kits. The comparative test results showed that three of the four commercial products tested gave very good levels of recovery and that the fourth commercial product gave only fair levels of recovery when the data were compared with the data from MOE P-A tests and membrane filter tests. P-A bottles showing positive results after 18 h of incubation that were subcultured immediately in ECMUG tubes frequently could be confirmed as containing total coliforms, fecal coliforms, or Escherichia coli after 6 h of incubation; thus, the total incubation time was only 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Aeromonas↗
PubMed1993

Modulation of Mu1 opioid binding by magnesium: evidence for multiple receptor conformations.

Previous studies have revealed that MgSO4 markedly increases mu1 binding and is associated with approximately a 10-fold slower dissociation rate, implying an increase in receptor affinity. Yet, saturation studies showed only a slight change in Kd values with a significant increase in the Bmax values. We now extend these observations using detailed kinetic approaches to better understand the role of MgSO4 on mu1 binding. Using blocking concentrations of the delta-selective ligand DPDPE, low concentrations of [3H]DADLE label mu1 sites almost exclusively in calf thalamic homogenates in the presence of either MgSO4 or EDTA, as demonstrated in competition studies. Saturation studies performed under equilibrium conditions with EDTA or MgSO4 reveal Bmax values of 1.89 +/- 0.20 and 4.4 +/- 0.19 fmol/mg wet weight tissue, respectively, with Kd values of 3.8 +/- 0.8 and 1.92 +/- 0.27 nM. Despite the small but significant 2-fold difference in Kd values under equilibrium conditions, kinetic studies reveal the dissociation rate constants (k-1) for the two assay conditions vary by almost 8-fold. NaCl increases the dissociation rate far more in assays performed in EDTA, while binding in the presence of MgSO4 is more sensitive to the stabilized GTP analog 5'-guanylylimidodiphosphate. Association studies also reveal a 20-fold difference between rate constants (k+1). The apparent association rate constants (kobs) in the presence of EDTA are concentration-dependent, whereas varying the concentration of [3H]DADLE has no effect on the rate constants under MgSO4 conditions. Our data suggest a model in which mu1 binding comprises two sequential steps and at least three distinct receptor binding states.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗