Failures in organization development: a focus on change agents and their responsibility.
Explore the source record for details and available documents.
Ethics, Institutional↗
Biomedical subjects
T C Smith
Publications and source records attributed to T C Smith.
Studies of human leprosy lesions in situ using suction-induced blisters. 2. Cell changes and soluble interleukin 2 receptor (Tac peptide) in reversal reactions.
To examine the pathogenesis of type 1 (reversal) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 10 patients with reactions, 24 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells and Tac-peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During reversal reactions: a) the lesions contained an increased number and percentage of CD4+ (T-helper) cells; b) Tac-peptide levels were elevated in half of the lesions; c) the increases in Tac peptide and CD4+ cells were directly correlated; and d) systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population. These findings were localized to the skin, and do not represent simple filtration of these components from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of CD4+ cells, is an important feature of reversal reactions, and may be an intermittent or cyclic phenomenon during the reaction. Findings in active patients without reactions are consistent with the hypothesis that differing states of immunologic equilibrium have been established in different portions of the leprosy spectrum. In reversal reactions we may, therefore, be examining immunologic processes set in motion when a pre-existing equilibrium has been upset by spontaneous, natural events. The mechanism of such spontaneous changes in immunity in leprosy is of considerable interest, not only to understand the reaction, but also to examine the underlying determinants of delayed-type hypersensitivity and cell-mediated immunity in leprosy and the potential for artificially manipulating these responses, as proposed with vaccines or immunotherapy.
Adult↗
An integrative approach to quality assurance.
Explore the source record for details and available documents.
Education, Nursing, Baccalaureate↗
Pulmonary capillary pressures during hypoxia and hypoxemia.
Explore the source record for details and available documents.
Humans↗
Quinine inhibits multiple Na+ and K+ transport mechanisms in Ehrlich ascites tumor cells.
The interaction of quinine with K+ and Na+ transport mechanisms has been investigated in Ehrlich ascites tumor cells. Quinine affects both Ca2+-dependent K+ channel and total K+ influx. Activation of Ca+-dependent K+ channels by propranolol is abolished by quinine (1 mM). In addition, quinine inhibits the ouabain-sensitive component of K+ influx with an apparent Ki of 0.32 +/- 0.02 mM and the furosemide-sensitive component with a Ki of 0.24 +/- 0.01 mM. Furthermore, a significant fraction (52%) of Na+ influx is inhibited by quinine. The same component is sensitive to amiloride, suggesting that it represents Na+/H+ antiport. Concomitant with the inhibition of K+ and Na+ transport, quinine stimulates ATP hydrolysis by 57%. The results suggest that quinine exerts broad, nonspecific effects on cellular mechanisms which serve to regulate cation transport in Ehrlich cells.
Adenosine Triphosphate↗
Validation of the use of the lipophilic thiocyanate anion for the determination of membrane potential in Ehrlich ascites tumor cells.
The utility of the lipophilic anion thiocyanate (SCN-) as a probe for the indirect estimation of the cell membrane potential (Vm) in Ehrlich ascites tumor cells has been evaluated by comparison to direct electrophysiological measurements. SCN accumulation is consistent with first-order uptake into a single, kinetically-identifiable cellular compartment, achieving steady-state distribution in 20-30 min at 22 degrees C. The steady state distribution ratio ([SCN-]e/[SCN-]e) in physiological saline is 0.44 +/- 0.02. Treatment of the cells with propranolol (0.13 mM), an activator of Ca2+ dependent K+ channels, reduces the steady-state distribution ratio to 0.19 +/- 0.02. Conversely, treatment with BaCl2 (10 mM), an antagonist of the pathway, increases the SCN- distribution ratio to 0.62 +/- 0.01. The equilibrium potentials (VSCN) calculated under these conditions are virtually identical to direct electrophysiological measurements of the Vm made under the same conditions. The effect of varying extracellular [K+] ([K+]e) in the presence of constant [Na+]e = 100 mM has also been tested. In control cells, elevation of [K+]e from 6 to 60 mM reduces VSCN from -20.6 +/- 1.0 to -13.2 +/- 1.2 mV. Again, microelectrode measurements give excellent quantitative agreement. Propranolol increases the sensitivity of the cells to varying [K+]e, so that a 10-fold elevation reduces VSCN by approximately 31 mV. BaCl2 greatly reduces this response: a 10-fold elevation in [K+]e yielding only a 4-mV reduction in VSCN. It is concluded that the membrane potential of Ehrlich cells can be estimated accurately from SCN- distribution measurements.
Animals↗
Experimental data acquisition and manipulation by microcomputer.
To improve experiment management, we developed a microcomputer system which automatically displays, collects, manipulates and stores data in real-time. Upon completion of all experiments, it automatically performs statistical analysis, prints graphs and stores the results. The components required to accomplish these tasks include: (1) a microprocessor and visual monitor; (2) transducers, each with preamplifier, filter and amplifier; (3) couplers from each amplifier to the computer; (4) software to direct display, manipulation, statistical analysis and storage of data; and (5) hardware to allow real-time graphic and hard copy display. The resulting system allows sampling rates up to 300 Hz and accuracy of 0.20% full scale, 0-200 mm Hg. It provides great flexibility, efficiency and reliability in data management, and thereby facilitates the organization and completion of research protocols. It simplicity of design and operation makes it easy to use, and it is extremely cost effective. We present a method of laboratory microcomputerization as a practical alternative for management of physiological experimentation.
Analog-Digital Conversion↗
Multiple-dose pharmacokinetics and pharmacodynamics of adinazolam in elderly subjects.
The pharmacokinetics and pharmacodynamics of adinazolam (AD) were evaluated in 21 elderly subjects (mean age, 69 +/- 4 years) at four dose levels during a placebo-controlled, double-blind, dose escalation regimen in which the oral dose was varied from 10 to 60 mg daily, in divided doses. Fifteen subjects received adinazolam mesylate; six received placebo. Plasma samples collected during a single dosing interval in each dosing period (3 days) were assayed for adinazolam and monodesmethyl adinazolam (NDMAD) by high-performance liquid chromatography (HPLC). Urine samples were collected during a single interval during the 20- and 40-mg daily dose periods and assayed for NDMAD by HPLC. Pharmacologic effects of adinazolam were assessed using psychomotor performance tests and sedation ratings. Adinazolam pharmacokinetics were linear over the dosage range studied. Daily dose had no significant effect on dose-normalized AUC and Cmax for AD. Dose-normalized NDMAD AUC values as well as beta values were not significantly affected by the daily dose of adinazolam. The ratio NDMAD/AD was not substantially affected by the dose. Renal clearance of NDMAD for the 20- and 40-mg daily doses were 5.6 +/- 2.1 and 5.5 +/- 2.2 liters/hr, respectively, and did not correlate with creatinine clearance. Adinazolam and NDMAD did not substantially accumulate in elderly subjects, even upon multiple dosing at 8-hr intervals. The dosing regimens in this experiment appeared to be well tolerated in the elderly, as performance tests and sedation scores indicated no substantial dose-related effects of adinazolam on psychomotor performance.
Aged↗
A methodology to monitor professional nursing practice.
Explore the source record for details and available documents.
Humans↗
Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy.
In order to address the question whether hypersensitivity reactions to dapsone are becoming more frequent, the clinical data of 7300 leprosy patients treated between 1949 and September 1988 at the McKean Rehabilitation Centre in Thailand were reviewed. Information from the period 1949 to 1969 was too incomplete to allow conclusions. The incidence of hypersensitivity reactions to dapsone between 1970 and 1982 was 0.3%. From 1982 (with the introduction of multidrug therapy) to September 1988, the incidence was 3.6%; a tenfold increase compared with the previous period. Of the 19 cases seen since 1982, 12 were diagnosed as Dapsone syndrome. Of a total of 13 patients seen since 1980 with Dapsone syndrome, 3 ended fatally, indicating the severity of the complication. The question is raised whether an unexplained drug interaction with rifampicin is responsible for the increase of hypersensitivity reactions to dapsone in patients treated for leprosy.
Adolescent↗
Hepatitis B antigen and antibody in patients with leprosy: a study of three resettlement villages in Thailand.
It remains uncertain whether the cellular immune abnormalities of patients with lepromatous leprosy interfere with resolution of hepatitis B virus (HBV) infections. To investigate this question in an area coendemic for the two diseases, we determined the prevalence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in: 1) 204 leprosy patients living in three leprosy resettlement villages; 2) 198 contacts living in the same villages; and 3) 44 newly diagnosed leprosy patients in Thailand. Within the villages, the prevalence of HBsAg positivity was inversely related to age, tended to be more frequent in patients with tuberculoid than lepromatous leprosy, and was similar after age adjustment among persons with and without leprosy. The prevalence of HBV markers found in newly diagnosed patients was similar to that in the villagers. We conclude that extensive HBV transmission had occurred in the resettlement villages and that the natural history of HBV infection was similar in persons with, whether tuberculoid or lepromatous, and without leprosy.
Adolescent↗
Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction.
Positive end-expiratory pressure (PEEP) has generally been withheld from the treatment of patients with chronic airflow obstruction (CAO), in view of the risk of hyperinflation and lack of documented benefit. We studied 10 mechanically ventilated patients with exacerbated CAO and air trapping to determine the impact of PEEP on lung mechanics, alveolar pressure, and the work of breathing. PEEP levels of 5 and 10 cmH2O were applied to patients whose end-expiratory alveolar pressures were documented to be positive when breathing against ambient pressure (the auto-PEEP effect). All patients were studied under two conditions: every breath machine assisted (AMV) and every breath machine controlled (paralyzed, CMV). PEEP improved expiratory resistance without substantially increasing peak static pressure. Inspiratory resistance remained unchanged. The difference between the end-expiratory values of alveolar and central airway pressure narrowed as PEEP increased. Adding PEEP improved the effective triggering sensitivity of the ventilator, diminished ventilatory drive, and reduced the mechanical work of breathing during the machine-assisted ventilatory cycle. Our results indicate that low levels of PEEP may improve lung mechanics and reduce the effort required of mechanically ventilated patients with severe airflow obstruction, without substantially increasing the hazards of hyperinflation.
Airway Resistance↗
External work output and force generation during synchronized intermittent mechanical ventilation. Effect of machine assistance on breathing effort.
We measured the mechanical work performed by 12 acutely ill patients during synchronized intermittent mandatory ventilation to determine the influence of volume-cycled machine assistance on inspiratory timing, respiratory muscle force development, and external work output. The frequency and tidal volume of spontaneous breaths increased at lower levels of mechanical ventilation, but inspiratory time fraction did not vary across the spectrum of machine support. As machine support was withdrawn, inspiratory work and pressure-time product increased progressively for both spontaneous and assisted breathing cycles. On a per cycle basis, work output was greater for assisted than for spontaneous breaths at all levels of comparison. Although the mean pressure developed by the patient during assisted cycles averaged approximately equal to 20% less than during adjacent unassisted cycles, contraction time averaged approximately equal to 20% longer, so that the pressure-time products were nearly equivalent for both types of cycle. Two indices of force reserve indicated that our patients taxed their maximal ventilatory capability at all but the highest levels of support. We conclude that under the conditions of this study the ventilatory pump continued to be active at all levels of machine assistance. Although work per liter related linearly to the proportion of minute ventilation borne by the patient, force generation differed little for spontaneous and machine-aided breaths at any specified level of support. Whether judged on the basis of mean developed pressure (work per liter of ventilation) or pressure-time product, little effort adaptation to volume-cycled machine assistance appears to occur on a breath-by-breath basis.
Humans↗
Energetics of Na+-dependent amino acid co-transport in Ehrlich ascites tumor cells.
The energy available from the Na+ electrochemical potential gradient (delta mu Na) has been evaluated in Ehrlich ascites tumor cells during accumulation of 2-aminoisobutyric acid. Cells were incubated in media of varying [Na+] (25-154 mM) in the presence of 0.25 mM 2-aminoisobutyric acid to establish maximum steady-state accumulation of the amino acid. Membrane potential (Vm) and intracellular Na+ activity (aNa) were estimated using standard electrophysiological techniques. In physiological saline ([Na+] = 154 mM) aNa is 4.4 +/- 0.6 mM, giving an apparent Na+ activity coefficient (gamma app) in the cytoplasm of 0.17 +/- 0.02. Vm under these conditions is -20.8 +/- 2.1 mV. From these values, delta mu Na = 9.9 +/- 0.8 kJ/mol. Concomitant determinations of 2-aminoisobutyric acid (AIB) accumulation show an energy requirement (delta mu AIB) of 8.5 +/- 0.5 kJ/mol. Stepwise reductions in extracellular [Na+] give parallel reductions in aNa, Vm and 2-aminoisobutyric acid accumulation. However, under all conditions tested the energy available from the Na+ electrochemical potential gradient exceeds that needed to drive 2-aminoisobutyric acid uptake. The effects of 2-aminoisobutyric acid on Vm have also been determined. Addition of AIB (10 mM) to steady-state cells leads to membrane depolarization (resting Vm = -22.1 +/- 1.3 mV; plus AIB Vm = -16.2 +/- 1.2 mV) within 1 min. Subsequent repolarization of the membrane to resting levels occurs within 10 min. The repolarization phase is blocked in the presence of ouabain (2 mM). The results establish that the energy available from the Na+ gradient is sufficient to serve as a source for 2-aminoisobutyric acid accumulation.
Amino Acids↗
Collection of leukocytes, fibroblasts, and collagen within an implantable reservoir tube during tissue repair.
An implantable chamber consisting of a small reservoir and a perforated segment of silicone tubing has been developed for the collection of leukocytes, fibroblasts, and collagen to analyze inflammatory components and fibroplasia during tissue repair. Using aseptic techniques, these sterile chambers were placed into subcutaneous pockets on the backs of Sprague-Dawley rats with cells obtained in daily aspirates for 14 d. Differential cell counts were made by using aliquots from the wound fluid. The aspirated cells represented the characteristic, sequential influx of neutrophils, inflammatory macrophages, lymphocytes, activated macrophages, and fibroblasts documented in other models of tissue repair. On d 14, the connective tissue within the lumen of the silicone tube was removed and analyzed for collagen synthesis by measuring 3H-proline incorporation into collagenase-sensitive protein. This new device for studying wound healing provides a convenient means to harvest cells, fluid, and tissue for cellular, humoral, and biochemical analyses of tissue repair.
Animals↗
Operative risk in coronary artery surgery study registry patients.
Explore the source record for details and available documents.
Coronary Vessels↗
Respiratory interactions of ketamine and morphine.
Six healthy, consenting volunteer males received ketamine iv in five logarithmically scaled doses totaling 3 mg/kg on three occasions each. The sessions differed only in the initial injection of an unknown drug: placebo, morphine sulfate 0.2 mg/kg, or morphine sulfate 0.4 mg/kg. Initial and terminal steady-state ventilatory responses to CO2 (VERCO2) and isohypercapnic ventilation (end-tidal CO2 49.8 +/- 2.4 mmHg) during drug administration assessed CO2-mediated ventilatory drive. Oxygen concentration of 40% ablated hypoxic drive contribution. Morphine caused a decrease of isohypercapnic ventilation (VE) of 8.2 +/- 1.2 l/min after 0.2 mg/kg. Doubling the dose to 0.4 mg/kg gave a further depression of 6.6 +/- 1.8 l/min. No subject lost consciouness after morphine. Over a dose range of 0.39 to 3.0 mg/kg ketamine caused log-linear dose-related depression of 1.6 +/- 0.3 l/min for each doubling of dose, although the first significant depression of 4.9 +/- 1.1 l/min did not occur until the third dose (1.1 mg/kg) in the absence of morphine. All subjects were unconscious after 1.8 mg/kg ketamine. Slopes of the VERCO2 did not differ from control, regardless of the pretreatment, placebo, or morphine in the two doses. Ketamine alone, 3.0 mg/kg, caused a displacement of VERCO2 of +2.0 +/- 1.2 mmHg in CO2, while combination of ketamine and morphine in either dose caused a +10 mmHg displacement of VERCO2. Thus, ketamine appears qualitatively similar but less potent than premedicant doses of morphine in depressing respiration despite near equipotency in producing loss of consciousness.
Adolescent↗