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Biomedical subjects

K Phillips

Publications and source records attributed to K Phillips.

At least 91 records · Page 5Linked to original sources
PubMed1995

Randomized clinical trial of antithymocyte globulin induction in renal transplantation comparing a fixed daily dose with dose adjustment according to T cell monitoring.

Antithymocyte globulin (ATG) has been used successfully for induction therapy as well as for treatment of established allograft rejection. However, this therapy has often been associated with problems of overimmunosuppression and increased costs. In a randomized clinical trial, we compared the immunosuppressive benefits, complication rates, and treatment costs when ATG is given as a fixed daily dose or when the dose is adjusted daily according to its biologic effects on T cells. Forty-five recipients of cadaver renal allografts were randomized into two groups. In group 1 (n = 23), ATG (ATGAM) was administered in variable doses to maintain the absolute number of peripheral CD3 T cells at 50-100/microliters. In group 2 (n = 22), ATG was given at a fixed dose of 15 mg/kg/day. All patients received azathioprine and prednisone. ATG was discontinued at 7-14 days when cyclosporine was introduced. In both groups, CD2, CD3, CD4, CD8, and CD19 cells were measured by flow cytometry and the levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, Il-7, and IL-10 were measured by ELISA. In group 2, the levels of all T cell subsets were profoundly suppressed. In group 1, the number of CD3 and other T cells was maintained at about 100 cells/microliters, while the CD19 T cells remained unsuppressed. Cytokine levels were greatly suppressed in group 2 compared with group 1, except for IL-10 levels, which remained elevated in the latter group. Patient survival, graft function, and the incidence of acute and recurrent rejections were similar in the two groups. Bone marrow suppression and infective complications were greater in group 2 than in group 1. The mean daily dose and the total quantity of ATG used in group 1 were significantly smaller than in group 2, resulting in a savings of $2,398.00 per patient per treatment. It is concluded that monitoring of ATG by its biologic effects on T cells is a rational and safe method of regulating the dose of this important agent; in this way, it is possible to reduce the total amount of the drug given to patients with consequent reduction in undesirable complications as well as in the cost of treatment without loss of immunosuppressive benefits.

Adult↗
PubMed1995

Quantitative genetic analysis of injury liability in infants and toddlers.

A threshold model of latent liability was applied to infant and toddler twin data on total count of injuries sustained during the interval from birth to 36 months of age. A quantitative genetic analysis of estimated twin correlations in injury liability indicated strong genetic dominance effects, but no additive genetic variance was detected. Because interpretations involving overdominance have little research support, the results may be due to low order epistasis or other interaction effects. Boys had more injuries than girls, but this effect was found only for groups whose parents were prompted and questioned in detail about their children's injuries. Activity and impulsivity are two behavioral predictors of childhood injury, and the results are discussed in relation to animal research on infant and adult activity levels, and impulsivity in adult humans. Genetic epidemiological approaches to childhood injury should aid in targeting higher risk children for preventive intervention.

Adult↗
PubMed1995

Risk factors for HIV and other sexually transmitted diseases and prevention practices among US heterosexual adults: changes from 1990 to 1992.

OBJECTIVES: The National AIDS Behavioral Survey (1990-1992) of heterosexual adults (18-49 years) measured human immunodeficiency virus (HIV) risk factors, condom use, and HIV antibody testing, with a focus on major "high-risk" cities. METHODS: A longitudinal survey was conducted. RESULTS: There was little reduction in the overall prevalence of HIV risk factors in the national or high-risk cities cohorts over time. Despite this picture of stability, approximately 39% of the population at risk for HIV because of multiple sexual partners turns over annually. There was little change in HIV test-seeking or in consistent condom use with primary sexual partners. Although the majority of at-risk respondents used condoms sporadically or not at all (65%), a significant increase in condom use was found among those reporting multiple sexual partners in both waves, particularly among Black heterosexuals. Data from other surveys and condom sales nationally support the findings. CONCLUSIONS: There is a need for a series of surveys in this area to assess the reliability of the present findings and to monitor the general US population's response to prevention programs.

Adolescent↗
PubMed1995

Severe anemia: a risk factor for glomerular injury in sickle cell disease.

Approximately 15% to 20% of patients with sickle cell disease have proteinuria. Proteinuria, particularly albuminuria, is the hallmark of glomerular injury. This study examines risk factors for glomerular injury as indicated by urinary albumin excretion (UAE) 30 microgram/minute, directly related to sickle cell disease. A total of seven patients were enrolled between September 1992 and March 1993. Fasting blood chemistries, complete blood cell count, 24-hour urine for protein and creatinine clearance, and glomerular filtration rate determined by 125 I-iothalamate were obtained for each patient. The results indicated that the lower the hematocrit, the higher the UAE rate. Low hematocrits have served as a protective mechanism in sickle cell disease by reducing blood viscosity and thus decreasing the number of vaso-occlusive crises. However, severe anemia appears to have an indirect adverse effect on the kidney in sickle cell disease.

Adult↗
PubMed1995

Encouraging drinking at safe limits on single occasions: the potential contribution of protection motivation theory.

Protection Motivation Theory (PMT) is considered as a possible framework for understanding and moderating higher-risk drinking. To this end questionnaire data were collected from 196 participants about levels of their current drinking and, after they have been alerted to the dangers of excess drinking on single occasions, their cognitions relating to drinking and their intentions for future single occasion drinking. Comparisons of higher and lower risk drinkers among the sample provided support for the applicability of PMT, revealing differences in their cognitions and in their adaptive and maladaptive coping. A supplementary path analysis revealed that health beliefs and coping strategies associated with PMT, together with demographics, account for 42% of the variance in behavioural intentions. These results suggest that PMT could prove a valuable tool for those working in alcohol research and education. Implications for the design of effective interventions are discussed.

Adult↗
PubMed1994

The Met repressor-operator complex: DNA recognition by beta-strands.

The crystal structure of the E. coli met repressor in complex with a synthetic 19-base pair oligonucleotide reveals two dimeric repressor molecules bound to adjacent sites on the DNA. The oligonucleotide contains two adjacent repeats of an 8-mer known as a met-box, which represents the consensus of the met operator sites. Each met repressor dimer is centered on a met box and interacts with the adjacent dimer through antiparallel alpha-helices, which explained the observed cooperative nature of the binding. DNA binding takes place through the insertion of a beta-ribbon into the major groove of B-form DNA, representing a novel DNA binding motif. Sequence specificity arises from direct interactions between side chains of the beta-strands and the edges of the bases in the major groove. The local DNA conformation confers additional specificity through interactions between protein and the phosphate backbone. The repressor is activated through binding of S-adenosyl methionine (SAM), the corepressor, to the face opposite to that used for DNA binding. The lack of significant conformational change upon SAM binding, together with electrostatic calculations, suggests that DNA binding enhancement occurs through long-range electrostatic interactions.

Bacterial Proteins↗
PubMed1994

Electrostatic activation of Escherichia coli methionine repressor.

BACKGROUND: The three-dimensional structure of the Escherichia coli methionine repressor (met repressor) is relatively unperturbed by the binding of its corepressor, S-adenosylmethionine (SAM), and of operator DNA. The positively charged corepressor binds to sites on the repressor remote from the DNA-binding site, and despite the lack of induced structural change is able to raise the affinity for operator DNA by a factor of up to 1000. Neutral corepressor analogues also bind to the repressor, but do not increase operator affinity. These observations suggest that the corepressor effect may be electrostatic. RESULTS: Using the program DELPHI, we have calculated electrostatic potentials for the repressor and its complexes, and have obtained results consistent with an electrostatic model for repressor activation. The positive potential originating from the corepressor is propagated through the repressor-operator complex, and is significant at DNA phosphate groups buried in the protein-DNA interface. The rank order of calculated electrostatic interaction energies for complexes with SAM, and two closely-related analogues, is in agreement with experimental measurements of the corresponding repressor-operator affinities. CONCLUSION: Long-range (> 10 A) electrostatic interactions between bound corepressor and operator phosphate groups in the repressor-operator complex may be sufficient to explain repressor activation Met repressor could, therefore, be an electrostatically triggered genetic switch.

Apoproteins↗
PubMed1994

Relationship of burst-forming-unit-erythroid progenitors and their DNA-synthesis stage to fetal hemoglobin levels in hydroxyurea-treated patients with sickle cell anemia.

DNA-synthesis stage and total number of circulating burst-forming-units-erythroid (BFU-E) have been inversely correlated with hemoglobin F levels in the peripheral blood, as well as in the cells from the BFU-E-derived colonies obtained from homozygous sickle cell anemia (SS) patients during steady state. Similar studies in SS patients treated with cytotoxic agents have not been reported. However, regeneration of the erythroid marrow that follows the cytoreduction phase of chemotherapy has been suggested as one of the mechanisms of stimulation of fetal hemoglobin synthesis. Therefore, a longitudinal study of hemopoiesis in hydroxyurea-treated SS patients was conducted. Thirty-two sets of hemopoietic studies, including total circulating BFU-E and S-phase BFU-E, were obtained from three patients treated with hydroxyurea. A dose-dependent decrease in total BFU-E colonies occurred in peripheral blood of all three patients (r = -0.58, -0.85, and -0.97, respectively, with each P < 0.05). There was a strong positive correlation between hydroxyurea dose and fetal hemoglobin levels in two of the three patients who responded clinically (r = 0.89618 and 0.88632, respectively, with each P < 0.01). When data from all patients were combined (n = 32), there was a strong, inverse, linear relationship between total number of BFU-E and percentage S-phase BFU-E with fetal hemoglobin levels (r = -0.6649 and -0.7404, respectively, with each P < 0.0001). A stronger, curvilinear, multiple relationship was detected between total BFU-E and percentage S-phase BFU-E with fetal hemoglobin levels (R = 0.8351 and 0.8602 with each P < 0.0001).

Adolescent↗
PubMed1994

Evaluation of a training course on sexual counselling in a drug work setting.

It has been repeatedly reported that while risks associated with the injecting behaviour of drug users has been reduced, no parallel changes have been made in sexual risk behaviour. Counselling advice to clients attending drug unit services has not focused sufficiently on the sexual behaviour of this client group. The present study evaluates the impact of a 4-day tailored training course on the counselling practices of two teams of drug workers at a London hospital. The course was designed following the experience and evaluation of a more general training course on sexual issues, and included information, group discussions, experiential learning and skills training. Results indicate that though there were no significant behavioural changes, some attitudinal changes have taken place; training appears to have increased the staff's awareness of the importance of sexual counselling and reduced the perceived difficulty of discussing certain specific sexual issues. The implications of single-agency training courses are discussed and recommendations are made for future training courses on the basis of the findings of this study.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Intestinal kinetics and dynamics of Escherichia coli heat-stabile enterotoxin in suckling mice.

The heat-stabile enterotoxin produced by Escherichia coli (ST) induces diarrhea by binding to receptors on intestinal cells, activating guanylyl cyclase, and increasing cyclic GMP. High- and low-affinity receptors for this toxin have been identified previously. ST induces intestinal secretion in suckling mice in picomole doses, suggesting a role for high-affinity receptors in this process. The present studies examine the relative roles of high- and low-affinity receptors in this process. The time course of changes in free ST concentrations in suckling mouse intestine was determined after intragastric inoculation. Also, binding characteristics of high- and low-affinity receptors and their coupling to guanylyl cyclase were defined in intestinal membranes from suckling mice. Intestinal concentrations of toxin and receptor binding characteristics empirically determined were used in a dynamic model correlating fractional occupancy of high- and low-affinity receptors with intestinal secretion to estimate their relative contributions to ST-induced diarrhea.

Animals↗
PubMed1994

'Nursing should become a research-based profession'--has it?

I decided to write this article to promote discussion among my colleagues after my experience of doing clinical research of my own. I did a small clinical trial on the use of Sea-Bands (wrist sweat bands) to put pressure on an acupuncture site to relieve postoperative nausea. This has been published in the Nursing Times. I am a theatre sister and have a reasonably academic background having obtained both an Open University BA and a teaching certificate plus a number of nursing courses. Therefore, I had good access to staff and patients and enough confidence to embark on the project. However, I had no experience in research work, and perhaps it is not surprising to find that there is no back-up within 'the system' to sustain this type of work. I went to everyone that I could think of for help and advice to formulate my data collection protocol. I gleaned small nuggets of advice from the local college of nursing, from the community research liaison doctor, and from the ethical committee chairman but it was a long hard slog which would have deterred me from starting had I realised at the outset how many hours of my own time it would take me.

Humans↗