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Biomedical subjects

V Andrews

Publications and source records attributed to V Andrews.

At least 19 recordsLinked to original sources

Secondary cytokine production by lymphoid cells used in cellular immunotherapy.

Interleukin-2 (IL-2) has been used extensively in cellular immunotherapy trials as a systemic activator of the immune system as well as an ex vivo stimulant for lymphoid cell function. Despite the measurement of several in vitro and in vivo immunologic parameters related to cellular immunotherapy, determinants of successful cellular immunotherapy remain unknown. To further delineate the consequences of exposing peripheral blood lymphocytes to high concentrations of IL-2, we assessed the supernatants of IL-2-activated peripheral blood lymphocytes for production of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). Exposure of normal monocyte-depleted peripheral blood mononuclear cells (PBMC) to IL-2 caused a dose-dependent increase in secretion of TNF and IFN-gamma which increased linearly after 48 h in culture. Analysis of positively selected, highly purified PBMC subpopulations exposed to IL-2 revealed that TNF-alpha and TNF-beta were produced by both CD3+ and CD16+ subpopulations but not by CD22+ cells. These studies were extended to supernatants obtained from PBMC cultures used in the adoptive cellular immunotherapy of patients with advanced cancer. Patients treated with lymphokine-activated killer (LAK) cell immunotherapy were classified as responders (N = 14) or non-responders (N = 17) to therapy. We found no significant difference in the production of TNF between responders and nonresponders (22 +/- 9 U ml-1 vs. 20 +/- 6 U ml-1), P > 0.05. However, LAK cell supernatants harvested from non-responders contained a significantly higher level of IFN-gamma (232 +/- 94 U ml-1) compared with responders (42 +/- 14), P < 0.05. Furthermore, the linear association between IFN-gamma and TNF-alpha production was different between these two response groups (rs = -0.19 for non-responders and rs = 0.48 for responders). These results suggest that secondary cytokine production by adoptively transferred lymphocytesmay play an important role in the host response to cellular immunotherapy.

Cells, Cultured

A centromere map of the X chromosome from trisomies of maternal origin.

A centromere map is derived from XXX and XXY trisomies of maternal origin. Preliminary data suggest reduced recombination in the tetrads giving rise to mei I nondisjunction, but an excess of recombination in the pericentric region. As in Drosophila, multichiasmate tetrads may be more at risk of nondisjunction than nullochiasmate tetrads.

Animals

MAP, an expert system for multiple pairwise linkage analysis.

The logic of a program for multiple pairwise linkage analysis under interference is set forth, including a seriation algorithm to obtain a trial order, a mapping bootstrap to improve the trial order, and three procedures for quality control to detect mistyping. This approach is compared with multipoint analysis under null interference, which substantially overestimates map length and cannot incorporate a variety of data.

Algorithms

The differential effects of inductions of worry, somatic anxiety, and depression on emotional experience.

One-hundred and twenty-eight subjects underwent inductions of emotions designed to elicit worrisome, depressed, somatically anxious, or neutral emotional states, and then they completed the Multiple Affect Adjective Checklist. Induction of worry was found to produce (a) moderate degrees of both anxiety and depression, (b) emotional profiles more highly correlated with those of depression and somatic anxiety than the correlation of depression and somatic anxiety profiles with each other, and (c) a subjective state containing no unique emotional features separate from that induced in depression and somatic anxiety. Whereas a discriminant function analysis correctly classified 70-85% of the subjects in the other three conditions, subjects who underwent the induction of worry were correctly classified at only chance level.

Anxiety

Methylcellulose for endothelial cell protection.

A randomised trial of three types of endothelial cell protection for patients undergoing posterior chamber intraocular lens implant is described. The results confirm the superiority of a viscoelastic fluid over air as a form of endothelial cell protection. No statistically significant difference was found between sodium hyaluronate and hydroxypropylmethylcellulose (HPMC). As the cost of sodium hyaluronate is prohibitive, a manufacturing technique for HPMC is given.

Adult

Air, methylcellulose, sodium hyaluronate and the corneal endothelium. Endothelial protective agents.

In a randomised trial the endothelial protective agent used during extracapsular cataract extraction and intraocular lens insertion was air in 19 eyes (group 1), methylcellulose in 25 eyes (group 2) and sodium hyaluronate in 22 (group 3). The cell population densities of each eye were estimated immediately before and three months after the operations to determine the degree of cell loss. Eyes showing mechanical (touch) damage on the second postoperative day were eliminated. The numbers of eyes in each group which showed a statistically significant cell loss were compared, and the mean cell losses in each group were tested for significant differences. It appears that air actually damages the endothelium while methylcellulose and Na-hyaluronate are not harmful, and afford a high, essentially equal degree of endothelial protection.

Adult

The significance of pancytopenia in miliary tuberculosis.

Patients with miliary tuberculosis accompanied by a pancytopenia rarely survive their disease. If the peripheral blood picture does recover it has been taken as an indication that there is no underlying haematological disease, and so re-examination of the bone marrow is not performed. A case is described where resolution of the pancytopenia occurred but a persisting haematological disease remained. Aspects of haematological disease associated with tuberculosis are discussed.

Aged

Pharmacokinetics and hemodynamics of amrinone in patients with chronic cardiac failure of diverse etiology.

The pharmacokinetics of amrinone and its relationship to ventricular function were assessed in 15 patients with chronic cardiac failure following the administration of a single 100 mg oral dose. Patients examined had Class II (1 patient), Class III (13 patients) and Class IV (1 patient) heart failure as characterized by the New York Heart Association classification. Blood samples were obtained following amrinone administration at selected times for 8 hours following the dose. Cardiac output was assessed serially for 5 hours following amrinone dosing. Mean (SD) peak plasma concentrations of amrinone (2.1 (1.1) mcg/ml) were obtained 0.5 to 2 hours after drug administration. The mean (SD) apparent oral clearance, apparent volume of distribution at steady state and half-life of amrinone were 0.23 (0.13) L/hr/kg, 1.2 (0.4) L/kg, and 4.8 (3.0) hr. Peak increases in cardiac index averaged 50% of baseline values and improvement was maintained at least 5 hours following amrinone dosing when compared to baseline cardiac index (p less than 0.05). Examination of the relationship between cardiac index corrected for baseline and amrinone plasma concentrations within individuals yielded strong and highly significant relationships (r greater than 0.90; p less than 0.025) in five patients, while in the remaining patients, either no relationship existed or insufficient data was available for analysis. When the data from all patients were pooled, a modest though significant relationship (r = 0.67; p less than 0.01) existed between cardiac index corrected for baseline and the post-absorptive, post-distributive amrinone plasma concentration. No difference in response to amrinone as a function of failure etiology or functional aerobic capacity was evident. Evaluation of the relationships between the mean improvement in cardiac index versus amrinone plasma concentration, as well as the time courses of these parameters indicate that the site of action of amrinone may be pharmacokinetically distinguishable from plasma and the tissues in instantaneous equilibrium with plasma.

Acetylation

Is topical haloperidol a useful glaucoma treatment?

A randomised, double blind, single dose study of topical haloperidol, a dopamine receptor blocking drug, was performed on 20 healthy volunteers. After its administration a modest reduction in intraocular pressure was recorded over the six-hour study period, but the difference was not significant at the p less than 0.05 level. Although dopamine blocking agents are effective in reducing intraocular pressure in experimental animals, topical haloperidol appears unlikely to be clinically useful in the treatment of glaucoma.

Administration, Topical

Milrinone in the treatment of chronic cardiac failure: a controlled trial.

This study examines the acute hemodynamic response to intravenous and oral milrinone in 12 patients with moderate to moderately severe heart failure. The patients received milrinone or placebo at random in an 8-week double-blind trial. Dosing level and schedule were determined by the hemodynamic results. Acute and chronic plasma samples for milrinone concentration were drawn from patients throughout the study. Milrinone was administered intravenously in successive doses of 25, 50, and 75 micrograms/kg. This resulted in a 16.5%, 12.5%, and 28.4% peak increase in cardiac index, with a concomitant 24%, 29%, and 38% decrease in pulmonary capillary wedge pressure. There were no significant relationships between any of the mean maximal hemodynamic values and milrinone plasma concentration. Six patients received milrinone and six patients received placebo; only five patients completed the blinded phase. There was no significant difference between the groups in exercise capacity, but the conditions of five of the six patients who received placebo deteriorated. In two of the patients who received milrinone the aerobic capacity improved greater than 2 cc/min/kg over baseline, and an additional two patients reported a marked subjective improvement. The results of this study indicate that oral milrinone in the management of patients with chronic cardiac failure would justify larger controlled studies.

Administration, Oral

Effect of ascorbic acid on plasma calcium in guinea pigs.

Ascorbic acid (246 mg/kg body weight/day) was administered orally to 9-week old female guinea pigs of the Hartley strain over a period of 20 months. The controls received 40 mg/kg body weight/day of ascorbic acid in the diet. Observations were made on body weight, food and water consumption, plasma ascorbic acid, and the total calcium and ionic calcium levels at various times during the growth of these animals. A second experiment was carried out when the guinea pigs were 18 months old. In addition to the oral intake, they received intraperitoneally 623 mg/kg body weight/day of sodium ascorbate for 6 weeks. With this treatment, the ascorbic acid intake for the test animals was 20 times that for the controls. The plasma ascorbic acid and calcium levels of these animals were measured during the treatment. In the ascorbic acid-treated animals, there was a significant elevation in plasma ascorbic acid level in comparison with the controls, but no substantial differences were observed in the body weight, total calcium or ionic calcium levels in the plasma. The results suggest that the administration of large quantities of ascorbic acid does not affect total calcium or ionic calcium levels in the plasma of these animals.

Animals

Amrinone in the treatment of chronic cardiac failure.

The efficacy and safety of oral amrinone were examined in 17 patients with moderately severe to severe heart failure that was refractory to standard medical therapy and vasodilators. The short-term and 28 week response to open amrinone therapy was assessed first, followed by a placebo-controlled, double-blind withdrawal study of two 13 week stages in nine patients. Rest and exercise ventricular function were determined before and after 32 hours of amrinone; aerobic capacity was serially assessed. After 2 hours, 1.64 mg/kg amrinone produced a 40% (p less than 0.001) increase in cardiac output and a 32% (p less than 0.02) decrease in pulmonary wedge pressure without altering heart rate or blood pressure. The exercise cardiac index-wedge pressure curve obtained 32 hours after the first oral dose was significantly shifted (p less than 0.05) above control values. A sustained improvement in maximal oxygen uptake was noted during long-term open amrinone therapy. Subsequently, seven of the patients randomized to placebo therapy had a significant deterioration of symptoms or exercise tolerance, or both. After 4 weeks of readministration of amrinone, clinical stability was once again established and exercise tolerance was improved by Weeks 8 to 16. Adverse effects of thrombocytopenia (one patient) and hepatic dysfunction (one patient) attributable to amrinone were observed. It is concluded that amrinone is effective in the long-term treatment of chronic cardiac failure.

Aged

Cardiotonic agents in the management of chronic cardiac failure.

Heart failure is a syndrome with distinct clinical signs and symptoms. The severity of cardiac failure and a deterioration in functional capacity can be determined by a progressive exercise test and by the noninvasive determination of maximum oxygen uptake. In patients with severe cardiac failure refractory to medica therapy, particularly those with cardiomyopathy or ischemic heart disease, survival is seriously compromised, resembling the most serious malignancy. Cardiotonic agents may be useful in improving the quality of life, provided that they are effective and are given sufficiently early in the course of the disease. Dobutamine given intravenously augments cardiac performance and improves renal function in patients with very advanced disease refractory to multiple diuretics; long-term survival, however, remains dismal. Amrinone appears to be a promising agent for the long-term treatment of chronic cardiac failure; the utility of pirbuterol, an oral catecholamine analog, remains to be determined.

Adult