Biomedical subjects

D K Martin

Publications and source records attributed to D K Martin.

At least 19 recordsLinked to original sources

PubMed1996

Kainic acid blocks a TTX-sensitive sodium channel in retinal horizontal cells of the turtle (Pseudemys scripta elegans).

The aim of this study was to investigate the effects of excitatory amino acids on channels found in horizontal cell membranes using patch-clamp techniques. We unexpectedly found that the excitatory amino acid receptor agonist, kainic acid, reversibly inhibited the transient tetrodotoxin (TTX)-sensitive Na+ current in isolated horizontal cell bodies and axons from the retina of the turtle (Pseudemys scripta elegans). The effect of kainic acid was antagonized by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Kainic acid activated a non-selective cation current, a finding that was consistent with previous reports, and which would account for the kainate induced depolarisation of these cells. The inhibition of the transient TTX-sensitive Na+ current by kainic acid might be important in the modification of the kinetics of responses to excitatory amino acid analogues often observed during intracellular recording from these cells.

Animals↗

PubMed1996

Some techniques for the analysis of work sampling data.

Work sampling is an observational technique that produces counts representing the number of times that an individual has been observed performing each of several tasks. These data are collected using either systematic or random times of observation, and typically exhibit correlation between repeated observations on the same individual, with the degree of correlation being a function of the amount of time elapsed between measurements. Using several recently developed statistical techniques, we illustrate how it is possible to carry out analyses of these nominal outcomes that account for the correlation between repeated outcomes. We use description of a work sampling study to motivate the techniques and we compare empirically results from analyses based on several different underlying assumptions.

Adult↗

PubMed1996

Chloride ion channels are associated with adherence of lymphatic endothelial cells.

We have examined the role of chloride ion channels as part of the control mechanism for adherence and growth of lymphatic endothelial cells. The chloride channel inhibitor N-phenylanthranilic acid (0.1 mM) inhibited the initial adherence of previously nonadherent cells in the period up to 3 hr following seeding onto gelatin-coated culture dishes. The potassium channel inhibitor 4-aminopyridine (1 mM) had no effect on the rate of cell adherence. N-Phenylanthranilic acid had no effect when added to confluent monolayers of cells that had been growing for 3 days. This, and the observation that N-phenylanthranilic acid did not affect the ultrastructure of the cells, suggested that plasma membrane chloride channels are involved in the initial signaling cascade triggered when lymphatic endothelial cells begin to adhere to a substrate.

Animals↗

PubMed1996

Risk factors for nonelective hospital readmissions.

We previously reported a predictive model that identified potentially modifiable risk factors for nonelective readmission to a county hospital. The objectives of this study were to determine if those risk factors were generalizable to a different population. We found that the previously reported risk factors were generalizable, and other potentially modifiable risk factors were identified in this population of veterans. However, further research is needed to establish whether or not the risk factors can be modified and whether or not modification improves outcomes.

Aged↗

PubMed1996

Candida albicans induces selective expansion of human T lymphocytes expressing the T-cell receptor variable region V beta 5.1.

Candida albicans is a common pathogen which can present major problems as an opportunistic skin pathogen in patients with immunodeficiency. The exact nature of the T cell responses to C. albicans is poorly understood. The purpose of this study was to determine whether C. albicans could stimulate the selective expansion of T lymphocytes expressing particular V beta gene segments. Human T lymphocytes stimulated in vitro with an extract of C. albicans were analyzed for T cell receptor V beta gene expression by using a quantitative PCR technique. We found that stimulation of peripheral blood mononuclear cells (PBMC) produced a selective increase in the expression of V beta 5.1 and 5.2 gene transcripts. Using cytofluorographic analysis with available anti-V beta monoclonal antibodies, we verified that there was a significant selective expansion (P = 0.035) of V beta 5.1 positive T lymphocytes in PBMC from six subjects stimulated in vitro with C. albicans. PCR analysis of V beta 5.1 expansion in 10 subjects showed increases in V beta 5.1 gene transcripts in 7/10 subjects. More importantly, analysis of the T cell infiltrate 48 h after intradermal injections with C. albicans also showed significant expression of V beta 5.1 in the infiltrates, along with the infiltration of V beta 8.1 + T cells. The selective expansion of V beta 5.1 bearing T lymphocytes in PBMC stimulated with C. albicans and in skin test reactions to C. albicans suggests that a restricted population of T cells react to C. albicans. Furthermore, our present data raise the provocative possibility that one or more antigens in C. albicans can act as a superantigen, producing selective expansion of a population of T lymphocytes bearing a particular V beta specificity.

Antibodies, Monoclonal↗

PubMed1996

Immunohistochemical and histochemical characterisation of epithelial cells of rabbit lacrimal glands in tissue sections and cell cultures.

The purpose of this study was to establish conditions for isolation and long term culture of acinar cells from the Harderian gland, and superior and inferior lacrimal glands of the rabbit and to compare the in vitro growth patterns of cultured cells from these glands. In order to determine the predominant cell type in the cultures, cells and tissue sections were stained using a variety of antibodies to cytokeratins, smooth muscle actin, and neuron specific enolase. Similarly, PAS and alcian blue histochemistry were used to test for the presence of mucins. The glands were excised and cells isolated using enzymatic digestion and then established in long term culture. Different media and substrata were trialed for suitability. When cultured on uncoated Costar plastic in DMEM/10%FBS, the pattern of cell growth was similar for all glands with distinct phases involving aggregation and migration out from the aggregates before cells died between 20 to 30 days. Immunohistochemical staining indicated that the cultures were of acinar cells with a small percentage of ductal cells. The acinar cells of the lacrimal glands in situ and in vitro stained with antibody MNF116 directed against cytokeratins 5, 6, 8 and 17 but did not stain for antibodies to cytokeratin 18. The reverse staining pattern was true for the Harderian gland. Sections from the white lobe of the Harderian gland showed islets of serous secreting cells which showed positive staining when MNF116 was used. In situ, PAS positive cells were found in a small number of demilunes in the superior and inferior lacrimal glands and also in cells of the intercalated ducts. Surprisingly, in culture nearly all cells, including those isolated form the Harderian gland became PAS positive. In this study we have demonstrated that acinar cells from the Harderian and lacrimal glands of rabbit can be isolated and maintained in culture for 20 to 30 days, and that despite dramatic morphological changes, these cells retain their distinctive phenotype as indicated by antibody staining to specific cellular structural proteins such as cytokeratins and actin. However, the cultured cells also begin to produce mucins as indicated by PAS staining.

Animals↗

PubMed1996

Characterization of the properties of cocaine in blood: blood clearance, blood to plasma ratio, and plasma protein binding.

As part of a study to examine cocaine disposition and interaction with ethanol, it was necessary to characterize various properties of cocaine in the blood of the experimental animal. All studies were conducted using blood from healthy adult male Sprague-Dawley rats. Cocaine was incubated in whole blood at 37 degrees C at concentrations of 500-4000 ng/mL. The apparent first-order rate constant for cocaine loss was independent of concentration. Blood clearance, calculated assuming blood volume to be 64 mL/kg, was estimated to be 0.056 +/- 0.003 mL/(min.kg); a value considerably smaller than estimates of systemic clearance. The addition of NaF increased the rate of loss to form benzoylecgonine, as a result of increased chemical degradation and as a consequence of increased pH (to pH 8.0 over 30 h). This NaF-enhanced degradation was abolished when NaF was added to blood buffered to pH 7.4. Ethanol had no influence on cocaine degradation, and there was no evidence of cocaethylene (ethylcocaine) formation. Blood to plasma ratios determined in spiked and authentic samples were constant (0.94-1.05 and 0.99-1.03, respectively) and independent of concentration (100-1500 ng/mL) and pH (7.2-7.6). This ratio was not influenced by NaF or ethanol. The unbound fraction (fu) of cocaine determined in spiked plasma varied from 0.62 to 0.63 over the concentration range (75-2025 ng/mL). Ethanol had no effect on binding. The values for fu determined from authentic blood samples taken from rats dosed intravenously with cocaine (10 mg/kg) ranged from 0.67 to 0.69 (over the concentration range 300-1500 ng/mL). Cocaine plasma protein binding was independent of concentration but depended upon plasma pH (fu, 0.765 and 0.486, at pHs 7.0 and 7.8, respectively.

Animals↗

PubMed1996

An intervention on discharge polypharmacy.

OBJECTIVE: To determine if providing a way to cancel pre-admission prescriptions would reduce the number of active drug prescriptions (RXs) at discharge. DESIGN: A randomized non-blinded clinical trial. SETTING: Inpatient acute medical service of a university affiliated Veterans Administration medical center. PARTICIPANTS: Twelve medicine ward teams were randomized to control and intervention groups. Patients controlled had been discharged from these teams during 12 weeks and were receiving outpatient medications from this facility at hospital admission; control = 180, intervention = 168. INTERVENTION: At discharge, intervention teams used a computer-generated drug list to cancel or renew previous outpatient RXs or to prescribe new medications. Control teams could not cancel outpatient drugs and wrote all medications on individual prescriptions. MEASUREMENTS: The difference between admission and discharge RXs. RESULTS: There were no significant differences in patients' age, sex, race, Charlson Index (CI), or LOS between patient groups at discharge. The intervention group had fewer RXs on admission (5.4 vs 6.2, P < .05) and at discharge was not significantly different (2.9 vs 2.9, P = .87) from the control group. CONCLUSIONS: Providing a method for canceling pre-admission medications did not reduce the number of RXs at discharge. Further research is needed to evaluate the appropriateness of the large increase in RXs from admission to discharge for patients in acute hospital settings.

Analysis of Variance↗

PubMed1996

Effect of the class III antiarrhythmic agent E-4031 on the ATP-sensitive potassium channel in rabbit ventricular myocytes.

The class III antiarrhythmic drug E-4031, a known blocker of the delayed rectifier potassium channel (IK), might also be capable of blocking the ATP-sensitive potassium channel (IKATP). We examined this possibility by studying the effect of E-4031 on single IKATP channels in membrane patches excised from ventricular myocytes that were obtained by standard enzymatic dissociation techniques from New Zealand white rabbits. In inside-out patches, E-4031 caused a dose-dependent block of IKATP with an EC50 of 31 +/- 1 microM, Hill coefficient of 0.89 +/- 0.24 and no effect on channel conductance. Open dwell-time kinetics were fitted by two exponential components, with E-4031 causing reduction of the longer time constant. In outside-out patches, the concentration of E-4031 required to produce blockade was much higher. We conclude that E-4031 blocks the ATP-sensitive potassium channel and that it does so from within the cytoplasm, with one-to-one channel binding stoichiometry. Single channel conductance is unchanged, but the longer time constant for the open state is reduced, which suggests that E-4031 may be an open channel blocker of intermediate to slow time course.

Adenosine Triphosphate↗

PubMed1995

Fetal tissue transplantation and abortion decisions: a survey of urban women.

OBJECTIVE: To describe women's attitudes and predicted behaviour regarding the potential for fetal tissue transplantation (FTT) to influence abortion decisions. DESIGNS: Self-administered questionnaire survey by mail. SETTING: Academic family practice in Toronto. PARTICIPANTS: Random sample of 475 women 18 to 40 years of age selected from the family practice registry of an urban teaching hospital. Family physicians were blind to their patients' participation, and investigators were blind to the subjects' identity. Forty questionnaires were undeliverable. Of the remaining 435, 272 (62.5%) were completed. Six of the women were over 40 years of age or did not indicate their age and were excluded, which left 266 (61.1%) questionnaires for analysis. OUTCOME MEASURES: Number of women who would (a) be more likely to have an abortion if they could donate tissue for FTT and (b) feel better or worse about choosing abortion if FTT were an option, and open-ended comments about the potential for FTT to influence abortion decisions. RESULTS: Of the 266 respondents 32 (12.0%) reported that they would be more likely to have an abortion if they could donate tissue for FTT, 178 (66.9%) stated that they would not be more likely to do so, and 56 (21.1%) were uncertain. Of the 122 who indicated that they would consider an abortion if they were pregnant, 21 (17.2%) stated that they would be more likely to have an abortion if they could donate tissue for FTT, 77 (63.1%) replied that they would not be more likely to do so, and 24 (19.7%) were uncertain. The women 25 to 33 years of age were more likely to be influenced by FTT than the younger or older women, and the women 18 to 24 years were more uncertain about the influence of FTT on abortion decisions than the older women. In written responses some of the women felt that FTT might make abortion decisions easier; many were troubled that FTT might be used to justify a morally problematic abortion decision and felt that FTT should not be used to justify abortion. CONCLUSION: The data, the first of their kind gathered from from women, suggest that some women's abortion decisions may be influenced by the option to donate tissue for FTT. Further research is necessary to explore the mechanism of influence.

Abortion, Induced↗

PubMed1995

Water transport in dehydrating hydrogel contact lenses: implications for corneal desiccation.

This article provides direct evidence that the rate of evaporation from the anterior surface of a hydrogen contact lens is related to the bulk water transport within the contact lens, analogous to diffusion-controlled evaporation. The evaporative flux of water from the anterior surface of a contact lens, with free access to water at its posterior surface, was greater for contact lenses of greater overall water content. Blockage of the water entry to the posterior surface of the contact lens reduced the evaporative loss from the anterior surface by 44%. These results suggested that a decrease in the rate of lens bulk water transport during wear would lead to a reduced evaporation rate from the anterior lens surface, for example, if the contact lens water content was reduced due to lipid and mucus adsorption. In addition, a rise in the external temperature of 1.3 degrees was required to produce a significant increase (2 SD) in the evaporative flux from the contact lenses. This suggests that the steady-state water content in vivo may not be significantly influenced by temperature cycling during blinking.

Contact Lenses, Hydrophilic↗

PubMed1995

Human macrophages contain a stretch-sensitive potassium channel that is activated by adherence and cytokines.

A variety of stimuli, including cytokines and adhesion to surfaces and matrix proteins, can regulate macrophage function, in part through changes in Ca(2+)- dependent second messengers. While fluctuation in intracellular Ca2+ is an important modulator of cellular activation, little attention has been paid to the roles of other ions whose cytoplasmic concentrations can be rapidly regulated by ion channels. To examine the role of ion channels in macrophage function, we undertook patch clamp studies of human culture-derived macrophages grown under serum-free conditions. The major ionic current in these cells was carried by an outwardly rectifying K+ channel, which had a single-channel conductance of 229 pS in symmetrical K(+)-rich solution and macroscopic whole-cell conductance of 9.8 nS. These channels opened infrequently in resting cells but were activated immediately by (i) adhesion of mobile cells onto a substrate, (ii) stretch applied to isolated membrane patches in Ca(2+)-free buffers, (iii) intracellular Ca2+ (EC50 of 0.4 microM), and (iv) the cytokine IL-2. Furthermore, barium and 4-aminopyridine, blockers of this channel, altered the organization and structure of the cytoskeletal proteins actin, tubulin and vimentin. These cytoskeletal changes were associated with reversible alteration to the morphology of the cells. Thus, we have identified an outwardly rectifying K+ channel that appeared to be involved in cytokine and adherence-mediated macrophage activation, and in the maintenance of cytoskeletal integrity and cell shape.

Cell Adhesion↗

PubMed1995

Primary care physician productivity: the physician factor.

OBJECTIVES: To model physician productivity as a function of clinic (support system) characteristics and physician characteristics and to model the time a physician spends with the patient as a function of patient characteristics. DESIGN: Observational study. SETTING: A general medicine clinic of a university-affiliated Veterans Affairs medical center. PATIENTS: A cohort of 2,520 patients having 2,721 consecutive outpatient visits to 56 physicians. MAIN OUTCOME MEASURES: Physician productivity defined as patients seen/physician/hour and time (minutes) spent with the patient. RESULTS: Physicians saw a mean (+/- SD) of 1.62 +/- 0.68 patients/hour. Clinic characteristics explained 8.2% of the variability of session-specific physician productivity. Controlling for clinic characteristics, a factor representing the physician explained an additional 55.4%. A model for overall physician productivity, using physician characteristics, explained 84.9% of the variance, and time spent with the patient was an important predictor. Modeling physician time with patients, patient characteristics accounted for only 7% of the variability. Controlling for patient characteristics, the individual physician again provided the greatest explanatory power, an additional 22.8% of the variability. CONCLUSIONS: Physicians' practice patterns, rather than clinic or patient characteristics, may account for most of the variation in physician productivity. Given the magnitude of the influence of individual practice patterns, interventions to increase productivity need to consider methods to affect physician behavior.

Appointments and Schedules↗

PubMed1995

Inhibition of ATP-sensitive potassium channels in cardiac myocytes by the novel class III antiarrhythmic agent MS-551.

The novel class III antiarrhythmic agent, MS-551, has recently been shown to attenuate the decrease in ventricular effective refractory period and to prevent the subsequent ventricular fibrillation induced by pinacidil and hypoxia in isolated perfused rabbit hearts (Friedrichs et al. 1994). We studied the effects of MS-551 on single ATP-sensitive potassium channels in isolated rabbit ventricular myocytes using standard patch-clamp methods. MS-551 in the range from 1 microM to 100 microM produced a concentration-dependent reduction of the open probability of the ATP-sensitive potassium channel, with an apparent ED50 of 30 microM. This reduced channel activity was due to a smaller number of channel openings per unit time, and the average duration of each opening of the channel was unaffected. This property of MS-551 is likely to be of most significance in ischaemic tissue, where the ATP-sensitive channels are thought to carry the predominant current that shortens the duration of the action potential.

Action Potentials↗

PubMed1994

A case manager intervention to reduce readmissions.

BACKGROUND: Acute hospitalizations represent substantial financial liability to closed health care systems. Among hospitalized patients, those with repeated admissions are high-cost users. Most managed care plans employ case management to control hospital use. This technique attempts to detect and fulfill unmet medical and social needs, intensify postdischarge care, identify and mobilize effective community services, and enhance primary care access. Despite the popularity of case management to control hospital use, few trials have examined its efficacy. METHODS: We conducted a randomized controlled trial of an intervention of case managers at a university-affiliated Veterans Affairs medical center. Six hundred sixty-eight patients aged 45 years or older who were discharged from the general medicine inpatient service, who had access to a telephone, and who received primary care at the hospital's clinics were randomized to the intervention (N = 333) and control (N = 335) groups. Within 24 hours of discharge, case managers mailed educational materials and access information to intervention patients, and within 5 days they called to review and resolve unmet needs, early warning signs, barriers to keeping appointments, and any readmissions. Case managers contacted intervention patients if they made no visits for 30 days. This resulted in a total of 6260 patient-case manager contacts. Control and intervention patients were followed up for 12 months. RESULTS: Intervention patients had more frequent visits per patient per month to the general medicine clinic (0.30 +/- 0.23 vs 0.26 +/- 0.22, P = .008), but we detected no significant differences between groups in nonelective readmissions, readmission days, or total readmissions. CONCLUSIONS: Frequent contacts for education, care, and accessibility by case managers using protocols were ineffective in reducing nonelective readmissions.

Aged↗

PubMed1994

A tetraethylammonium-insensitive inward rectifier K+ channel in Müller cells of the turtle (Pseudemys scripta elegans) retina.

Ion channels present in isolated glial (Müller) cells from the retina of the turtle (Pseudemys scripta elegans) were studied with the patch clamp technique. The predominant conductance in these cells was due to an inward rectifying potassium current. The whole-cell conductance of the inward rectifier was 20.2 +/- 1.9 nS (n = 7 cells) in a standard extracellular saline solution (3 mM extracellular potassium). This conductance was dependent on the extracellular potassium concentration, with a 2.88-fold change in conductance per tenfold shift in concentration. The relative permeability sequence to potassium of the inward rectifier was found to be: potassium (1.0) > rubidium (0.7) > ammonium (0.2) > lithium (0.1) = sodium (0.1), which corresponded to the Eisenman sequence IV or V for a strong-field-strength potassium binding site on the channel. The single channel conductance measured in cell-attached patches with potassium chloride (150 mM) in the pipette was 68.5 +/- 6.0 pS (n = 3 patches). The inward rectifier current was not blocked by extracellular tetraethylammonium (TEA+, 20 mM), but was blocked by extracellular barium (5 mM) or cesium (5 mM). The TEA+ insensitivity of the inward rectifier potassium channel in Müller cells is unusual, given that this type of channel in most excitable cells is sensitive to micromolar concentrations of this compound, and may be a characteristic of inward rectifier potassium channels that are primarily involved with extracellular potassium regulation.

4-Aminopyridine↗

PubMed1994

The give and take of organ procurement.

Scientific developments of the last 20 years have made the transplantation of cadaveric solid organs a viable and expected treatment alternative for patients suffering from various forms of End Stage Organ Disease. Of the number of organs that could be utilized for this, only a small percentage of them are actually made available. North American legislation explicitly categorizes the transfer of cadaveric organs as an anatomical or tissue "gift". The concept of the gift is mediated by transculturally consistent unwritten, but powerfully felt, rules of conduct. Among the most profound elements of the concept is the obligatory gift-exchange which is central to the gift-relationship. Obviously, neither of these are permitted by the organ transplant scenario. As a result, dissonance is created within the thought process of the individual which cannot be easily resolved, paralyzing many into inaction. We maintain that the present legal framework, designed to facilitate the transfer of organs, clashes with the human phenomenon of giving, and may actually prevent organs from being made available. In a search for a solution to this gift-relationship dilemma, giving organs is contrasted with taking organs as a basis upon which to ground ethically sound public policy. Liberty-limiting principles and the concept of harm are considered within this context.

Bioethics↗

PubMed1994

Effects of disopyramide and flecainide on the kinetics of inward rectifier potassium channels in rabbit heart muscle.

1. Standard patch-clamp techniques were used to study the interaction of therapeutic concentrations of flecainide and disopyramide with single inwardly-rectifying potassium channels in cell-attached membrane patches from rabbit ventricular myocytes. 2. Under drug-free conditions, the potassium channels had a conductance of 31 +/- 2 pS (n = 13), a mean open time of 230 +/- 6 ms (n = 11) recorded at the resting cell potential, and an open probability of 0.66 +/- 0.20 (n = 39). The resting potential of the cells studied was -68.5 +/- 3.6 mV (n = 32). 3. Disopyramide did not reduce the open probability of the channel when the cell was voltage-clamped at the resting cell potential. However, disopyramide increased the mean open time of the channel, recorded at the resting cell potential, by 15% at 5 microM and by 29% at 20 microM. The action potential prolonging actions of disopyramide in therapeutic concentrations appear not to be due to blocking the inward rectifier K+ channel. 4. Flecainide (3.0 microM, but not at 0.5 microM) decreased the open probability without changing the conductance of the channel, at 3 microM (51.0 +/- 7.2%, n = 6, P = 0.03) at the resting cell potential. Flecainide increased the mean open time of the channel, recorded at the resting cell potential, by 12% at 3.0 microM. 5. We propose that flecainide stabilized the inward rectifier K+ channel in an inactivated state, without plugging the conducting pore. In addition, it appeared to bind to an open conformation of the channel,since some of the reduction in open probability could be accounted for by the lengthening of the mean open time. The changes in open-state kinetics suggest that this binding may be in the region of the activation gate.

Animals↗