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Biomedical subjects

D K Martin

Publications and source records attributed to D K Martin.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1994

Effect of glucocorticoids on tumor necrosis factor induced suppression of protein synthesis in rat aortic smooth muscle: comparison with extensor digitorum longus.

Protein synthesis was measured in incubated aortic smooth muscle and fast-twitch extensor digitorum longus (EDL) in both sham operated and adrenalectomized (ADX) rats. The studies were performed on four groups: a) untreated controls; b) rats treated with tumor necrosis factor (TNF) @ 50 micrograms/kg. b.w.; c) rats treated with cortisone @ 100 mg/kg/day for 5 days; or d) rats treated with cortisone plus TNF. Both TNF and cortisone suppressed protein synthesis in the aortic smooth muscle and EDL in intact animals. TNF given together with cortisone, induced a significant additional decrease in protein synthesis in both muscle types as compared to cortisone-treated rats. The rate of protein synthesis in aortic smooth muscle from sham operated rats was control > TNF > cortisone > Cortisone+TNF; in the case of EDL, rate was control > cortisone > TNF > Cortisone+TNF. In ADX animals, TNF alone did not affect protein synthesis in both aortic smooth muscle and EDL. Though cortisone alone produced a significant inhibition of protein synthesis, there was no significant further decline in protein synthesis when cortisone was given together with TNF. These findings suggest that the inhibitory effect of TNF on muscle protein synthesis is mediated through glucocorticoids.

Animals↗
PubMed1993

Small conductance chloride channels in acinar cells from the rat mandibular salivary gland are directly controlled by a G-protein.

This paper reports a 5pS Cl- channel in endpiece cells from the rat mandibular gland. The anion selectivity of the channel was SCN- > (Br- = I-) > NO3- > Cl-, which was similar to whole-cell recordings of a macroscopic anion conductance in these cells. The channel was activated by intracellular Ca2+ at depolarising potentials, with no significant activation when the membrane patch was hyperpolarised. The channel was directly activated by an Al/F complex and GTP gamma S, in separate experiments, applied to the cytosolic face of inside-out excised patches. These G-protein activators stimulated the Cl channel when the Ca2+ concentration was below 1nM, and suggests that this channel may be coupled directly to a G-protein in the apical membrane.

Aluminum↗
PubMed1993

Replication of the multidimensionality of activities of daily living.

We attempted to replicate the three-dimensional factor structure of a previously proposed ADL scale and demonstrate an association between the advanced ADL dimension and cognitive function. Data used in these analyses were baseline assessments of health and functional status of hospitalized patients enrolled in a randomized controlled trial of case managers as a means of reducing health care utilization. We submitted 14 items from the OARS to a two-stage process of principal components factor analysis. Four significant dimensions emerged that were remarkably similar to the advanced, basic, and household ADL dimensions reported by Wolinsky and Johnson (1991). In this sample of hospitalized patients, however, incontinence emerged as a weak fourth dimension. Multiple regression of SPMSQ mental status examination scores on these ADL dimensions demonstrates the association between cognitive function and the advanced ADL dimension. These data confirm that the underlying structure of ADLs consists of at least three separate dimensions, one of which is aligned with cognitive capacity.

Activities of Daily Living↗
PubMed1993

Tissue-specific and substrate-specific endoproteolytic cleavage of monkey pro-opiomelanocortin in heterologous endocrine cells: processing at Lys-Lys dibasic pairs.

This study compares the processing of pro-opiomelanocortin (POMC) at two Lys-Lys cleavage sites, located in the carboxy-terminal domain of the precursor, one site marking the amino terminus of beta-melanocyte-stimulating hormone (beta-MSH) and the other in the carboxy-terminus of beta-endorphin (beta E). These comparisons were carried out by transfecting monkey POMC cDNA into two heterologous cell lines: AtT-20, which endogenously expresses mouse POMC, and Rin m5F, which has been previously used as a host for transfected POMC. These cells lines are known to process POMC differently at Lys-Arg residues, though less is known about their Lys-Lys cleavage. Our results have demonstrated both tissue-specific and site-specific factors controlling Lys-Lys cleavage. The AtT-20 line appears not to perform either Lys-Lys cleavage. Rin m5F cells, on the other hand, fail to process the site at the carboxy terminus of beta E (beta E28-29) but do process, to a significant extent, the N-terminal site to beta-MSH. That this differential processing is unlikely to be due to a POMC conformation which would make the beta E site inaccessible was demonstrated by mutating the sites from Lys-Lys to Lys-Arg. With such mutants, Rin m5F cells fully processed at both locations. Interestingly, the mutant Lys-Arg sites were not fully processed by AtT-20 cells. These results are discussed in terms of the complement of processing enzymes expressed in each of the cell lines, as well as the role of residues surrounding the diabasic cleavage sites in determining the likelihood of proteolysis.

APUD Cells↗
PubMed1991

Standards for the electronic transfer of clinical data: progress and promises.

Data exchange standards have two components: the message format or syntax and the dictionary of codes (semantics). For many applications, message standards already have been developed. For a few kinds of clinical entities, such as drugs, these code systems (e.g., the National Drug Code) are virtually complete, but a few gaps must be filled and an agreement must be reached about the level of granularity needed. The available codes for clinical descriptors are inadequate but the National Library of Medicine's Universal Medical Language (UML) project will do much to redress this deficiency. Codes for clinical variables such as blood pressure and blood glucose which have methods, units, normal ranges, and physiologic correlates are very inadequate. CPT4 provides some of the needed codes but has huge gaps. An early effort to extend CPT4 is included in ASTM 1238. Work being done by ASTM E31.12 and the Euclides project will offer robust codes for clinical laboratory measurements. If we want to pool data from different institutions for clinical and policy research, universal codes for observations are prerequisite. And agreement of an international coding system for observation-bearing variables should be a major agenda item for standards groups in the next year. Our goal has been to standardize the communication of clinical data between clinical systems, not the systems themselves or their internal operation. In fact, standardizing the internals of clinical application could be counterproductive at the present. It would deflect energy from, and delay the spread of, CDI standards. Moreover, it gives undue attention to computer systems, rather than the data they contain. The data are the most expensive part of any data system. They are the raison d'être for such systems. Computer systems come and go. The data last forever. Yet we have been mesmerized by the computer system while ignoring its contents. As a result, most computer-stored clinical data must live like the tragic boy in the bubble. They cannot "live" outside of the computer system in which they were born. So, we find at every hospital the bizarre rituals of humans reading computer-generated reports so they can type this information in another computer. Electronic (e.g., stored clinical) data should not depend upon the internals of a particular program, language, or machine for its interpretation. The clinical data entered into one computer system should be directly available to any other computer system that now receives them through manual transcription. Data interchange standards give life to our data--independent of the source system.

Abstracting and Indexing↗