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Biomedical subjects

J Myers

Publications and source records attributed to J Myers.

At least 127 records · Page 7Linked to original sources
PubMed1994

Pharmacology of high-threshold calcium currents in GH4C1 pituitary cells and their regulation by activation of human D2 and D4 dopamine receptors.

1. The objective of this study was to characterize the pharmacology of calcium currents in GH4C1 pituitary cells and determine whether activation of heterologously expressed human dopamine receptors can regulate their function. Human D2(short), D3 and D4.2 receptor cDNA's were separately transfected into GH4C1 cells and whole cell calcium currents were recorded by use of nystatin-perforated patch clamp techniques. 2. High-threshold calcium currents were antagonized in a biphasic manner by the dihydropyridine, nisoldipine. The half-maximally effective concentration for each site was 0.2 nM (pIC50 = 9.78 +/- 0.21, n = 4) and 339 nM (pIC50 = 6.47 +/- 0.12, n = 4). The component of current inhibited by 10 nM nisoldipine was also blocked by omega-conotoxin GVIA (30 +/- 9% at 30 nM, n = 6) or by omega-agatoxin IVA (34 +/- 7% at 100 nM, n = 4). 3. Activation of either D2 or D4 receptors by dopamine (10 microM) or quinpirole (0.1 to 10 microM) reduced the peak calcium current by ca. 20% in the majority of cells studied. No inhibition was observed in control or D3 transfected GH4C1 cell lines. 4. The mobilisation of intracellular calcium by thyrotropin releasing hormone in hD4-GH4C1 cells was also studied using Fura-2 AM microspectrofluorimetry. Thyrotropin releasing hormone caused a concentration-dependent increase in calcium mobilisation with an EC50 of 7 nM. D4 receptor activation had no effect upon either basal or hormone-induced [Ca2+]i transients. 5. These results demonstrate that GH4C1 pituitary cells have at least two types of dihydropyridine sensitive high-threshold calcium currents and that like D2 receptors, human D4 receptors can also regulate calcium channel function.

Animals↗
PubMed1994

Depression of high-threshold calcium currents by activation of human D2 (short) dopamine receptors expressed in differentiated NG108-15 cells.

1. This study examined the regulation of calcium currents in differentiated NG108-15 cells that had been stably transfected with cDNA encoding the short isoform of the human D2 dopamine receptor. Whole cell calcium currents were recorded by nystatin-perforated patch clamp recording. 2. Transient low-threshold calcium currents elicited by depolarizations from -100 mV to -20 mV were reversibly depressed by NiCl2 (84 +/- 8% at 30 microM; n = 3) and by omega-agatoxin IVA (15 +/- 5%; 100 nM, n = 7). These currents were unaffected by hD2 receptor activation. 3. High-threshold calcium currents elicited by depolarizations from -80 mV to 0 mV were partly blocked by omega-conotoxin GVIA (67 +/- 6% at 100 nM, n = 4) and by the subsequent addition of the dihydropyridine, nisoldipine (94 +/- 3% at 1 microM). Consistent with the presence of at least two distinct types of high-threshold calcium channels, nisoldipine alone (38 +/- 15% at 1 microM, n = 6) did not preclude the inhibition caused by omega-conotoxin GVIA (69 +/- 13% at 100 nM, n = 4). The residual current was completely blocked by 100 microM CdCl2 (98.8 +/- 0.4%, n = 7). 4. In hD2-transfected cells, but not untransfected cells, high-threshold currents were depressed by quinpirole (30 +/- 4% at 100 nM; n = 15) with a pEC50 of 8.61 +/- 0.22 (n = 5), as well as by (-)-noradrenaline (28 +/- 5% at 1 microM, n = 9). Responses to both agonists were selectively antagonized by S-(-)sulpiride (100 nM) but not by the alpha-adrenoceptor antagonist, phentolamine (1O microM). The depression caused by (-)-noradrenaline was positively correlated with that of quinpirole for each cell(r2 = 0.91, slope = 0.99).5. hD2-receptor-mediated inhibition of high-threshold calcium currents was abolished by pretreatment of cells with omega-conotoxin GVIA (100 nM; n = 4). However, a component of the high-threshold current was reversibly depressed by omega-conotoxin GVIA (67% to 45% depression after 10 min wash). This current was also depressed by hD2 receptor activation (59 +/- 9% depression in 100 nM quinpirole, n = 3),and was completely blocked by nisoldipine (95 +/- 2% at 1 MicroM).6. These data demonstrate that activation of hD2(short) dopamine receptors can regulate both wconotoxinGVIA, and dihydropyridine-sensitive high-threshold calcium currents in neuroblastoma cells.Morever, the ability of human D2 dopamine receptors to regulate more than one type of calcium current supports the notion that these receptors have a diverse functional role in the central nervous system.

Animals↗
PubMed1994

The cytomegalovirus-antigenemia assay in the diagnosis of posttransplant cytomegalovirus infection.

Cytomegalovirus (CMV) infection continues to be a major cause of morbidity and mortality in transplant recipients, yet prompt diagnosis remains a problem. A new assay has been developed that detects CMV antigens in peripheral blood leukocytes (CMV-AG). A retrospective analysis of the experience with this assay was performed, and its usefulness in the diagnosis of CMV infection in renal transplant recipients with unexplained fever was compared with that of conventional modalities (buffy coat culture, detection of circulating anti-CMV immunoglobulin M). The results suggest that the CMV-AG assay is a more rapid and sensitive test than existing modalities in the early diagnosis of CMV infection. When expressed quantitatively, it can discriminate between CMV infection and CMV disease, and it is useful in monitoring the course of infection and the response to therapy.

Antigens, Viral↗
PubMed1994

Effects of reinforcement history on responding under progressive-ratio schedules of reinforcement.

The effects of experimental history on responding under a progressive-ratio schedule of reinforcement were examined. Sixteen pigeons were divided into four equal groups. Groups 1 to 3 were trained to peck a key for food under a fixed-ratio, variable-ratio, or differential-reinforcement-of-low-rate schedule of reinforcement. After training, these pigeons were shifted to a progressive-ratio schedule, later were shifted back to their original schedule (with decreased rates of reinforcement), and finally were returned to the progressive-ratio schedule. Pigeons in Group 4 (control) were maintained on the progressive-ratio schedule for the entire experiment. To test for potential "latent history" effects, pigeons responding under the progressive-ratio schedule were injected with d-amphetamine and given behavioral-momentum tests of prefeeding and extinction. Experimental histories affected responding in the immediate transition to the progressive-ratio schedule; response rates of pigeons with variable-ratio and fixed-ratio histories were higher than rates of pigeons with differential-reinforcement-of-low-rate and progressive-ratio-only histories. Pigeons with differential-reinforcement-of-low-rate histories, and to a lesser degree pigeons with variable-ratio and fixed-ratio histories, also had shorter postreinforcement pauses than pigeons with only a progressive-ratio history. No consistent long-term effects of prior contingencies on responding under the progressive-ratio schedule were evident. d-Amphetamine and resistance-to-change tests failed to reveal consistent latent history effects. The data suggest that history effects are sometimes transitory and not susceptible to latent influences.

Animals↗
PubMed1994

Increase in blood lactate during ramp exercise: comparison of continuous and threshold models.

Controversy persists regarding the mechanism underlying the lactate threshold. It has recently been argued that there is in fact no "threshold" and that blood lactate increases as a continuous function during exercise (Hughson J. Appl. Physiol. 62:1975-1981, 1987). In comparing continuous and threshold models, questions have been raised regarding the ramp rate, data sampling, and the mathematical models employed (Morton J. Appl. Physiol. 67:885-888, 1989). To address some of these concerns, we evaluated 61 subjects (mean age 45 +/- 15), who underwent maximal ramp treadmill tests with the ramp rate individualized such that test duration was approximately 10 min for each subject. The relationship between changes in blood lactate and oxygen uptake were evaluated using a modification of the log-log transformation model described by Beaver (J. Appl. Physiol. 59:1936-1940, 1985) and a continuous exponential plus constant model described by Hughson et al. (J. Appl. Physiol. 62:1975-1981, 1987). Model fitting, using mean squared error (MSE) and coefficient of determination (CD) for each method were as follows: [table: see text] The modified log-log model had a better fit as indicated by the lower MSE and higher CD, suggesting the change in lactate was better described by this model. However, the differences were so slight as to suggest: 1) a meaningful difference does not exist between the two; or 2) these methods may not be capable of detecting a difference, if one exists.

Adult↗
PubMed1993

Effects of sublingual nitroglycerin on the gas exchange response to exercise in stable angina pectoris.

To quantitate changes in gas exchange variables that occur after administration of sublingual nitroglycerin in patients with stable angina pectoris, a randomized double-blind 2-period crossover study was performed with continuous expired gas exchange analysis and progressive exercise using individualized ramp treadmill protocols. Significant reductions in minute ventilation and respiratory rate were observed at 5 minutes of exercise during nitroglycerin therapy. Gas exchange variables i.e., minute ventilation, carbon dioxide production and oxygen uptake were significantly increased at the onset of angina after nitroglycerin administration. When techniques for optimizing the assessment of cardiopulmonary function were used, significant improvements in gas exchange variables were demonstrated in stable angina pectoris after administration of sublingual nitroglycerin.

Administration, Sublingual↗
PubMed1993

Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study.

BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival.

Adult↗
PubMed1993

A cross-sectional survey of neurobehavioral effects of chronic solvent exposure on workers in a paint manufacturing plant.

Neurobehavioral impairments in 84 workers with long-term exposure to organic solvents in a paint manufacturing plant were examined cross sectionally. The World Health Organization (WHO) Neurobehavioral Core Test Battery, the NES-2 computerized battery, and four additional South African tests were used. Exposure to solvents was determined by using company industrial hygiene data as well as from an industrial hygiene survey of current total solvent levels in air. Indexes for cumulative exposure and average lifetime intensity of exposure were calculated for groups of homogeneously exposed workers in each department. Exposure levels were below the AGGIH threshold limit values. Multiple linear regression revealed that education level, age, and alcohol consumption were strong predictors for several neurobehavioral test scores. After adjusting for potential confounding from this source, average lifetime intensity of solvent exposure was the most significant predictor of the NES-2 Continuous performance test (measuring sustained visual attention) score of the WHO Digit span backward test score (measuring attention span and double tracking). Pursuit aiming (measuring fine visuomotor tracking speed) was significantly associated with the cumulative exposure index, possibly indicating early neurotoxic effects.

Central Nervous System↗
PubMed1993

Neuropsychological assessment of organic solvent effects in South Africa: test selection, adaptation, scoring, and validation issues.

The neurobehavioral effects of organic solvent exposure were assessed in 68 South African workers in a paint manufacturing plant in which the maximum current combined solvent level in workplace air was 0.72 of the Threshold Limit Value. A 17-test battery was assembled from the WHO-NCTB, NES 2, and the University of South Africa Neuropsychological Assessment Procedure. Extensive modifications were made to some tests in the battery, using a guided learning rationale derived from the cross-cultural literature. In light of test correlations with demographic variables (age, education, and alcohol consumption), the construct and likely predictive validity of the tests in the battery are reviewed, and promising procedures identified. Finally, it is noted that in developing countries, the results of neuropsychological tests that have been well standardized in the West may be misleading unless the underlying validity issues that arise when a test developed in one culture is applied to another have been addressed.

Adult↗
PubMed1993

Hemodynamic determinants of exercise capacity in chronic atrial fibrillation.

To evaluate the response of patients with chronic atrial fibrillation (AF) to exercise, 79 male patients (mean age 64 +/- 1 years) with AF underwent resting two-dimensional and M-mode echocardiography and symptom-limited treadmill testing with ventilatory gas exchange analysis. Patients were classified by underlying disease into five subgroups: no underlying disease (LONE: n = 17), hypertension (HT: n = 11), ischemic heart disease (n = 13), cardiomyopathy or history of congestive heart failure (CHF: n = 26), and valvular disease (n = 12). A higher maximal heart rate than expected for age was observed (175 vs 157 beats/min), which was most notable in the LONE and HT subgroups. Maximal oxygen uptake (VO2 max) was lower than expected for age in all groups. Patients with CHF had a lower resting ejection fraction than all other patients (p < 0.001), a lower VO2 max, and a lower maximal heart rate than LONE and HT patients (p < 0.001). Stepwise regression analysis demonstrated that echocardiographic measurements at rest were poor predictors of VO2 max and VO2 at the ventilatory threshold. Among clinical, morphologic, and exercise variables, maximal systolic blood pressure accounted for the greatest variance in exercise capacity, but it explained only 35%. In patients with AF the higher than predicted maximal heart rates may be a compensatory mechanism for maintaining exercise capacity after the loss of normal atrial function. However, even in the absence of underlying disease, it does not appear to compensate fully for a compromised exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Nomogram based on metabolic equivalents and age for assessing aerobic exercise capacity in men.

OBJECTIVES: The goal of this study was to create a nomogram, based on maximal exercise capacity (in metabolic equivalents [METs]) and age, for assessing a patient's ability to perform dynamic exercise to quantify the level of physical disability or relative capacity for physical activity. BACKGROUND: Providing an estimation of exercise capacity relative to age is clinically useful. Such an estimate can be derived from measured or estimated maximal oxygen uptake (in METs) from treadmill exercise testing and age. It is an effective means of communicating to patients their cardiopulmonary status, encouraging improvement in exercise capacity and quantifying disability. METHODS: Exercise test results of 1,388 male patients (mean age 57 years, range 21 to 89) free of apparent heart disease who were referred for exercise testing for clinical reasons were retrospectively reviewed. This referral group as well as subgroups of active (n = 346) and sedentary (n = 253) patients were analyzed to determine norms for age and for age by decades for exercise test responses, including METs, maximal heart rate and maximal systolic blood pressure. Regression equations were calculated from this information, and a nomogram for calculating degree of exercise capacity from age and MET level achieved by a patient was created. A similar analysis was performed in a separate group of 244 apparently healthy, normal male volunteers (mean age 45 +/- 14 years, range 18 to 72) who underwent exercise testing with direct measurement of expired gases. RESULTS: Equations for predicted METs for age were derived for the entire clinical referral group (METs = 18.0-0.15[Age]) and for the subgroups of active (METs = 18.7-0.15[Age]) and sedentary (METs = 16.6-0.16[Age]) patients. All results achieved statistical significance, with p values < 0.001. In the volunteer group of normal men who performed exercise testing with ventilatory gas exchange, the decline in maximal heart rate and METs with age was not as steep as in the referral group. Although the normal group confirmed nomograms published previously among similar subjects, the equations derived from the patients differed from those previously reported; in contrast to previous studies using healthy volunteers, the equations and nomograms for the referral group are more appropriate for patients typically referred for testing in a hospital or office-based internal medicine practice. CONCLUSIONS: Norms for METs based on age are presented as well as population-specific nomograms that enable physicians to assess patients' exercise capacity relative to their age group.

Adult↗
PubMed1993

Predictors of disease severity and survival in patients with coronary artery disease.

BACKGROUND: The objective of this study was to determine whether coronary angiographic findings and survival could be predicted using standard clinical and exercise-test data. METHODS: Five hundred and ninety-five men who had undergone both exercise treadmill testing and cardiac catheterization were followed for up to 5 years. Left main (LM) disease (> or = 50% stenosis) was present in 42 patients, whereas 30 patients had LM equivalent disease (> or = 70% stenosis of both the proximal left anterior descending and circumflex coronary artery disease (n = 152), one-vessel disease (n = 186), two-vessel disease (n = 118), three-vessel disease (n = 67), LM or LM equivalent disease without significant (> or = 70%) right coronary artery involvement (n = 26), and LM or LM equivalent disease with right coronary artery involvement (n = 46). RESULTS: ST-segment depression was more marked, whereas ejection fraction, maximal heart rate, maximal systolic blood pressure, and exercise capacity were lower in each group as disease severity worsened. Using Kaplan-Meier analysis, the subgroup with the poorest survival was found to be those with LM or LM equivalent disease with right coronary artery disease, and the next worse was the three-vessel disease group, in which survival was poorer than in all other subgroups (P < 0.01). Stepwise regression analysis revealed that the most powerful predictor for coronary artery disease severity was exercise-induced ST depression (P < 0.001), but it predicted survival poorly. History of congestive heart failure, low ejection fraction (50% or lower), and poor exercise capacity (5 metabolic equivalents or less) emerged as strong predictors of survival using stepwise Cox regression analysis (P < 0.001). CONCLUSION: Exercise-induced ST depression predicted the severity of angiographic disease but not survival, whereas the strongest predictors of survival were history of congestive heart failure, low ejection fraction, and poor exercise capacity.

Adult↗
PubMed1993

Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma.

PURPOSE: Eighteen patients with recurrent or refractory CD21-positive, non-Hodgkin's lymphoma (NHL) were treated in a phase IA dose-escalation therapeutic trial of iodine 131 labeled to a fixed dose of OKB7. METHODS: Individual doses of 30 to 50 mCi of 131I on 25 mg OKB7 were administered 2 to 3 days apart to achieve four total 131I-OKB7 dose levels of 90, 120, 160, and 200 mCi. Pharmacology, dosimetry, therapeutic effects, toxicity, human anti-mouse antibody (HAMA) response, and maximum-tolerated dose (MTD) were determined. Patients were evaluated by imaging studies (including whole-body gamma camera or single-photon emission computed tomography [SPECT] scans), flow cytometric analysis, bone marrow biopsy, and serial blood sampling. RESULTS: Median plasma and whole-body half-lives (T1/2) were 16 hours and 14 hours, respectively. Plasma and whole-body radiation doses were 0.0081 Gy/mCi and 0.0022 Gy/mCi, respectively. Specific tumor visualization was noted in eight of 18 patients. HAMA was detected in 12 of 16 patients. Nonhematologic toxicity was limited to asymptomatic elevations of thyroid-stimulating hormone (TSH) in five of 15 patients. Hematologic toxicity was observed in six of 18 patients, but was severe in only two patients. MTD in patients with diffuse lymphomatous bone marrow involvement was determined to be 200 mCi in four divided doses of 50 mCi 131I/25 mg OKB7. Antitumor activity was observed in 13 of 18 patients (one partial response [PR] and 12 mixed responses) and was dependent on the 131I-OKB7 dose administered. In general, palpable peripheral lymphadenopathy, enlarged spleens, skin lesions, and circulating OKB7-positive peripheral lymphocytes responded most readily to treatment. 131I-OKB7 was safely administered to a patient in leukemic phase of NHL with prompt subsequent loss of approximately 1 kg of tumor cells from the peripheral blood without associated tumor lysis syndrome. CONCLUSION: Because antitumor activity with tolerable toxicity was observed in the majority of this group of heavily pretreated patients, phase II investigation of mAb OKB7 radioconjugates in the therapy of NHL is warranted.

Adult↗
PubMed1993

Cardiac rehabilitation in Switzerland. Efficacy of the residential approach following bypass surgery.

BACKGROUND: The traditional central European approach to cardiac rehabilitation involves sending patients to an idyllic setting, where they reside for a specified period following a cardiac event. Favorable results have been demonstrated using this approach in Germany, but to our knowledge no data have been reported from Switzerland, where these programs tend to be short (4 weeks) and exercise training is concentrated (2 h daily, 6 days per week). METHODS AND RESULTS: Seventeen patients (aged 58 +/- 6 years) who resided in a rehabilitation center for 4 weeks were compared with 11 patients (aged 54 +/- 7 years) given usual community care beginning approximately 6 weeks after coronary artery bypass surgery (CABS). Exercise training consisted of 1 h of group walking twice daily, with the intensity stratified into 4 levels based on clinical status and initial exercise capacity. All patients underwent pulmonary function testing and maximal ramp exercise testing on a cycle ergometer with continuous ventilatory gas exchange and lactate analysis before and after the study period. Patients receiving beta-blockers and those with cardiomyopathy or valvular heart disease were excluded. Medication status was not changed during the study period. Although maximal oxygen uptake increased by approximately 12 percent within both groups, the change was not significant between groups. Analysis of variance demonstrated that mean lactate levels were reduced throughout exercise within both groups (p < 0.001); however, there were no differences between groups. Oxygen uptake at the lactate threshold was not different in either group after the study period. CONCLUSIONS: Similar changes occur in the functional status of post-CABS patients regardless of their participation in the short but concentrated rehabilitation programs common in Switzerland, suggesting that these programs either begin too soon after CABS or are too short to achieve training benefits.

Coronary Artery Bypass↗
PubMed1993

Solvent exposure, alcohol consumption and liver injury in workers manufacturing paint.

Liver enzyme activity was examined in 89 South African paint makers currently exposed to a mixture of organic solvents at fairly low levels. However, the duration of exposure was substantial for many. Fifty-eight workers (65%) had at least one enzyme value above the upper reference limit. Gamma glutamyl transferase (gamma GT) activity was elevated in 46% of the workers and aspartate aminotransferase (ASAT) in 52%. In a comparison between workers with high and low solvent exposure, the gamma GT and ASAT values were higher in the most exposed group (eg, gamma GT mean 108 versus 69 U.l-1, P > 0.05). Adjustment for confounding by alcohol consumption and body mass index eliminated the differences due to exposure. It was concluded that the measures of liver injury used did not demonstrate solvent-induced hepatic damage but that excessive alcohol consumption was an important factor.

Adult↗