Search PubMed⌕ Search

Biomedical subjects

R S Phillips

Publications and source records attributed to R S Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1994

The impact of serious illness on patients' families. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: To examine the impact of illness on the families of seriously ill adults and to determine the correlates of adverse economic impact. DESIGN: Data were collected during the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT), a prospective cohort study of outcomes, preferences, and decision making in seriously ill hospitalized adults and their families. SETTING: Five tertiary care hospitals in the United States. PARTICIPANTS: The 2661 seriously ill patients in nine diagnostic categories who survived their index hospitalization and were discharged home were eligible for this analysis. Surrogate and/or patient interviews about the impact of illness on the family were obtained for 2129 (80%) of these patients (mean age, 62 years; 43% women; 6-month survival, 75%). OUTCOME MEASURES: Surrogates and patients were surveyed to determine the frequency of adverse caregiving and economic burdens. Multivariable analyses were performed to determine correlates of loss of family savings. RESULTS: One third (34%) of patients required considerable caregiving assistance from a family member. In 20% of cases, a family member had to quit work or make another major life change to provide care for the patient. Loss of most or all of the family savings was reported by 31% of families, whereas 29% reported loss of the major source of income. Patient factors independently associated with loss of the family's savings on multivariable analysis included poor functional status (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.10 to 1.78 for patients needing assistance with three or more activities of daily living), lower family income (OR, 1.74; 95% CI, 1.37 to 2.21 for those with annual incomes below $25,000), and young age (OR, 2.85; 95% CI, 2.13 to 3.82 for those younger than 45 years compared with those 65 years or older). CONCLUSIONS: Many families of seriously ill patients experience severe caregiving and financial burdens. Families of younger, poorer, and more functionally dependent patients are most likely to report loss of most or all of the family's savings.

APACHE↗
PubMed1994

Effect of computer-based alerts on the treatment and outcomes of hospitalized patients.

BACKGROUND: Hospital computing systems play an important part in the communication of clinical information to physicians. We sought to determine whether computer-based alerts for hospitalized patients can affect physicians' behavior and improve patients' outcomes. METHODS: We performed a prospective time-series study to determine whether computerized alerts to physicians about rising creatinine levels in hospitalized patients receiving nephrotoxic or renally excreted medications led to more rapid adjustment or discontinuation of those medications, and to determine whether such alerts protected renal function. RESULTS: Laboratory data were observed for 20,228 hospitalizations, with documentation of 1573 events (instances of rising creatinine levels during treatment with a nephrotoxic or renally excreted drug). During the intervention period, doses were adjusted or medications discontinued an average of 21.6 hours sooner after such an event (P < .0001). For patients receiving nephrotoxic medications during the intervention period, the relative risk of serious renal impairment was 0.45 (95% confidence interval, 0.22 to 0.94) as compared with the control period, and the mean serum creatinine level was 14.1 mumol/L (0.16 mg/dL) lower on day 3 (P < .01) and 25.6 mumol/L (0.29 mg/dL) lower on day 7 (P < .05) after an event. Forty-four percent of physicians who responded to a questionnaire said that the alerts had been helpful in the care of their patients, whereas 28% found them annoying. Sixty-five percent wished to continue receiving alerts. CONCLUSIONS: Computer-based alerts regarding patients with rising creatinine levels affect physician behavior, prevent serious renal impairment, preserve renal function, and are accepted by clinicians.

Acute Kidney Injury↗
PubMed1994

Malaria parasites undergo antigenic variation at high rates in vivo.

The rates of switching between expression of variable antigen types (VATS) have been investigated in vivo in a cloned line of Plasmodium chabaudi chabaudi. VAT-specific hyperimmune sera combined with an immunogold-silver staining technique were used to detect VATS, and five estimates of VAT-specific switching rates were determined for three of them. VAT-specific switching rates were consistent for each VAT and differed between VATS in the range 1.3 x 10(-2) to 4.3 x 10(-4) switches per schizont per generation. This variation suggests that hierarchical expression of VATS in an infection may be determined by switch rates. A minimum estimate of the overall switching rate was determined by summation of the VAT-specific rates in each of two experiments. In both cases the results showed that at least 1 in every 80 schizonts switched VAT expression every generation. This is the first report of antigenic switching rates for malaria parasites measured in vivo in the presence of minimal specific immune pressure, and is the first to show that VAT-specific switching rates vary between VATS. We conclude that switching is rapid and spontaneous, and is regulated, at least in part, by the VATS involved.

Animals↗
PubMed1994

Improved visual function and attenuation of declines in health-related quality of life after cataract extraction.

OBJECTIVE: To measure the effect of cataract extraction and lens implantation on elderly persons' health-related quality of life and on their ability to perform visual activities. DESIGN: Evaluations of health status were conducted preoperatively and at 3 and 12 months after surgery on patients scheduled for cataract extraction. SETTING: Patients were enrolled from the General Eye Service of the Massachusetts Eye and Ear Infirmary and 33 Boston practices. PATIENTS: The cohort consisted of 464 patients aged 65 years or older who were identified from the surgical schedule of the Massachusetts Eye and Ear Infirmary. At 3 to 12 months after surgery, 458 (99%) of the participants were successfully contacted. Health-related quality of life data were available for 419 (90%) to assess changes after surgery. MAIN OUTCOME MEASURES: Ophthalmologic examinations were performed preoperatively and during the follow-up period. The Activities of Daily Vision Scale (ADVS) and the Medical Outcomes Study 36-item short from (SF-36) were administered before surgery and at 3 and 12 months postoperatively to assess changes in health status. RESULTS: At 12 months after surgery, 95% of patients had improved Snellen visual acuity, 80% had improved ADVS scores, but only 36% had improved SF-36 physical functioning. Average scores on seven of eight SF-36 subscales worsened at 12 months. Patients with improved ADVS scores had significantly smaller declines across all SF-36 dimensions except for role limitations due to emotional problems. CONCLUSION: Improved visual function after cataract surgery was associated with better health-related quality of life, suggesting that age-related declines in health may be attenuated by improvements in visual function.

Activities of Daily Living↗
PubMed1994

Th1 and Th2 CD4+ T cell clones specific for Plasmodium chabaudi but not for an unrelated antigen protect against blood stage P. chabaudi infection.

The host protective immune response to blood stage malaria infection was studied using Plasmodium chabaudi chabaudi (P.chabaudi) in NIH mice. It has been shown previously that CD4+ cells are critically required for protection against erythrocytic infection. Mice lacking a functional CD4+ cell compartment suffer unremitting patent primary parasitemias for at least 60 days after infection. Here, we report that the adoptive transfer of eight P. chabaudi-specific CD4+ T cell clones of either the Th1 or Th2 type to mice rendered CD4-depleted by adult thymectomy and anti-CD4 monoclonal antibody therapy fully restored the ability of recipients to control challenge infection. Control Th1 and Th2 clones specific for an unrelated antigen, ovalbumin, were unable to confer a comparable level of protection in CD4-depleted mice, even though they received regular doses of the antigen. These data demonstrate that protective immunity to asexual P. chabaudi parasites can be mediated through immune CD4+ T cell clones of either the Th1 or the Th2 subset.

Animals↗
PubMed1994

Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells.

The balance between T helper type 1 (Th 1) and T helper type 2 (Th2) cells determines the outcome of many important diseases. Using cloned murine T cell lines, evidence is provided that Th1, but not Th2, cells can be activated by specific antigens or a T cell mitogen, concanavalin A, to produce large amounts of nitric oxide (NO). Furthermore, NO can inhibit the secretion of interleukin (IL)-2 and interferon-gamma by Th1 cells but has no effect on IL-4 production by Th2 cells. Th1 and Th2 cells can, thus, be distinguished by their differential production of and susceptibility to NO. NO exerts a self-regulatory effect on Th1 cells which are implicated in immunopathology.

Animals↗
PubMed1994

Predominance of infected reticulocytes in the peripheral blood of CD4+ T-cell-depleted mice chronically infected with Plasmodium chabaudi chabaudi.

The distribution of Plasmodium chabaudi chabaudi AS among normocytes and reticulocytes in the peripheral blood of NIH mice undergoing a primary infection was determined from brilliant cresyl blue/Giemsa's stained thin blood films. During the early stages of infection in normal mice, parasites were found exclusively in normocytes. The presence of parasites in reticulocytes was limited to a period of severe immune pressure on the parasites, peak parasitaemia and the ensuing "crisis" phase, at which time the rapid production of new erythrocytes in response to the anaemia in these mice resulted in a high reticulocyte count. Later, during the recrudescence, parasites inhabited normocytes only. Thus, in immunologically competent animals, P. c. chabaudi AS showed no absolute preference for either mature or immature erythrocytes. In marked contrast, in chronically infected CD4+ T-cell-depleted mice, this malaria parasite apparently displayed a pronounced predilection for reticulocytes. During an unremitting parasitaemia of 2.8%-3.9% during days 13-60 post infection, all parasites were found in reticulocytes, even though these comprised only 25% of the total erythrocyte count. The possible reasons for this reversal in preference for the type of erythrocyte inhabited by asexual malaria parasites are discussed.

Animals↗
PubMed1994

Prior capacity of patients lacking decision making ability early in hospitalization: implications for advance directive administration. The SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

OBJECTIVE: To investigate the appropriateness of hospitalization as the time to elicit patients' medical care preferences, the authors evaluated the capability of seriously ill patients to participate in decision making early in hospitalization and their decision making capacity two weeks before hospital entry. DESIGN: Cross-sectional study with retrospective evaluation of preadmission decision making capacity. SETTING: Five acute care teaching hospitals. PATIENTS: Four thousand three hundred one acutely ill hospitalized adults meeting predetermined severity of illness criteria in nine specific disease categories. MEASUREMENTS: Surrogate decision makers' estimates of the prior mental capacities of patients unable to be interviewed early in hospitalization about care preferences due to intubation, coma, or cognitive impairment. Comparison of the demographics, degrees of sickness at admission, and outcomes of interviewable vs noninterviewable patients. MAIN RESULTS: Forty percent of the patients were not interviewable concerning preferences. Of these, 83% could have participated in treatment decisions two weeks prior to hospitalization. The patients who were not interviewable were more acutely ill, had less chronic disease, and were more likely to die during hospitalization than the interviewable patients. CONCLUSIONS: Many acutely ill patients likely to die in the hospital lost their ability to make medical care decisions around the time of hospital admission. Preferences for care and advance directives should be discussed in the outpatient setting or very early in hospital admission.

Advance Directives↗
PubMed1994

B cells are required for the switch from Th1- to Th2-regulated immune responses to Plasmodium chabaudi chabaudi infection.

The induction of T-helper cell subsets during the course of blood stage Plasmodium chabaudi chabaudi infection was compared in immunologically intact NIH mice and mice that were depleted of B cells from birth by treatment with anti-mu antibodies. For intact mice, in which the acute primary parasitemia peaked 10 days following infection, purified splenic CD4+ T cells recovered during the ascending parasitemia produced high levels in vitro of interleukin 2 (IL-2) (peak levels on day 10) and gamma interferon (IFN-gamma) (peak levels on day 7). Sera collected from these mice at around this time contained relatively high levels of P. c. chabaudi-specific immunoglobulin 2a (peak levels on day 12), and serum nitric oxide activity was significantly elevated at peak parasitemia. During the descending primary parasitemia, production of IFN-gamma and IL-2 decreased, while levels of IL-4 and IL-10 produced by splenic CD4+ T cells were significantly raised from the time at which subpatency was recorded (day 17) and persisted for at least 50 days. This was concomitant with a significant increase in levels of parasite-specific immunoglobulin G1, which peaked at around the time of recrudescence. Thus, in normal mice, sequential appearance of Th1 and Th2 responses was observed. In contrast, in B-cell-depleted mice, recovery from acute primary parasitemia was followed by a persistent patent infection which did not drop below 0.1% for at least 75 days after initiation of infection. These mice were unable to mount a significant Th2 response, manifest as an enduring inability of splenic CD4+ T cells to produce significant levels of IL-4 and IL-10. IL-2 and IFN-gamma levels remained significantly elevated throughout the 50-day observation period, and there was sustained production of nitric oxide. These data show that immune responses mediated by CD4+ T cells of the Th1 subset are capable of limiting infection beyond the initial acute phase, but that they do not eliminate parasitemia. Furthermore, as the progression from a Th1-regulated to a Th2-regulated immune response fails to occur in B-cell-depleted mice, the data suggest that B cells are required for the downregulation of Th1-mediated and/or the generation of Th2-mediated protective immunity to P. c. chabaudi.

Animals↗
PubMed1994

Expression of the IL-1 receptor discriminates Th2 from Th1 cloned CD4+ T cells specific for Plasmodium chabaudi.

The expression of selected interleukin receptors by cloned CD4+ T cells specific for the murine malaria parasite Plasmodium chabaudi chabaudi (P. chabaudi) representative of the T-helper (Th) 1 and Th2 subsets was examined. Both sets of clones expressed receptors for those interleukins for which they had a growth factor requirement in vitro. Each Th1 clone expressed receptors for, and was responsive to, interleukin (IL)-2 and IL-4, while each Th2 clone expressed receptors for, and was responsive to, IL-2, IL-4 and IL-1. IL-1 receptor (IL-1R) expression by the Th1 clones was either negligible or could not be detected. The disparity in expression of IL-1R by the Th1 and Th2 clones was more clear-cut than has been previously reported and IL-1R provided a definitive phenotypic marker for clones of the Th2 subset. Should IL-1R expression prove to be a feature of other Th2 cells cultured long-term in vitro, this will be invaluable for investigations involving the phenotyping, depletion or selection of CD4+ T cells of either Th1 or Th2 subset.

Animals↗
PubMed1993

Binding of phenol and analogues to alanine complexes of tyrosine phenol-lyase from Citrobacter freundii: implications for the mechanisms of alpha,beta-elimination and alanine racemization.

We have examined the interaction of Citrobacter freundii tyrosine phenol-lyase with both L- and D-alanine. This enzyme catalyzes the racemization of alanine as a side reaction, in addition to the physiological beta-elimination of L-tyrosine to give phenol and ammonium pyruvate. The steady-state kinetic parameters for alanine racemization, kcat and Km, for D-alanine are 0.008 S-1 and 32 mM, respectively, while those for L-alanine are 0.03 S-1 and 11 mM. Incubation of tyrosine phenol-lyase with either L- or D-alanine forms a quinonoid complex that exhibits a strong peak at 500 nm. The presence of K+ increases the intensity of the 500-nm absorption with L-alanine, but decreases the intensity of the peak with D-alanine. Rate constants for the formation of these quinonoid intermediates and the effects of phenol and analogues on the reaction with either L- or D-alanine have been studied by rapid-scanning and single-wavelength stopped-flow spectrophotometry. Phenol binds to all the intermediates of tyrosine phenol-lyase with L- and D-alanine, but most strongly to the external aldimine complex, resulting in a decrease in the absorbance at 500 nm at equilibrium. Pyridine N-oxide binds selectively to the quinonoid complex of alanine, and thus causes an increase in the absorbance at 500 nm at equilibrium. 4-Hydroxypyridine causes a decrease in absorbance at 500 nm during the fast phase, but an increase in absorbance at 502 nm in a subsequent slow relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1993

The role of TH1 and TH2 cells in a rodent malaria infection.

CD4+ T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both TH1 and TH2 subsets of CD4+ T cells can protect mice against Plasmodium chabaudi chabaudi infection. TH1 cells protect by a nitric oxide-dependent mechanism, whereas TH2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.

Animals↗
PubMed1993

Three-dimensional structure of tyrosine phenol-lyase.

Tyrosine phenol-lyase (EC 4.1.99.2) from Citrobacter freundii has been cloned and the primary sequence deduced from the DNA sequence. From the BrCN digest of the NaBH4-reduced holoenzyme, five peptides were purified and sequenced. The amino acid sequences of the peptides agreed with the corresponding parts of the tyrosine phenol-lyase sequence obtained from the gene structure. K257 is the pyridoxal 5'-phosphate binding residue. Assisted by the sequence data, the crystal structure of apotyrosine phenol-lyase, a pyridoxal 5'-phosphate-dependent enzyme, has been refined to an R-factor of 16.2% at 2.3-A resolution using synchrotron radiation diffraction data. The tetrameric molecule has 222 symmetry, with one of the axes coincident with the crystallographic 2-fold symmetry axis of the crystal which belongs to the space group P2(1)2(1)2 with a = 76.0 A, b = 138.3 A, and c = 93.5 A. Each subunit comprises 14 alpha-helices and 16 beta-strands, which fold into a small and a large domain. The coenzyme-binding lysine residue is located at the interface between the large and small domains of one subunit and the large domain of a crystallographically related subunit. The fold of the large, pyridoxal 5'-phosphate binding domain and the location of the active site are similar to that found in aminotransferases. Most of the residues which participate in binding of pyridoxal 5'-phosphate in aminotransferases are conserved in the structure of tyrosine phenol-lyase. Two dimers of tyrosine phenol-lyase, each of which has a domain architecture similar to that found in aspartate aminotransferases, are bound together through a hydrophobic cluster in the center of the molecule and intertwined N-terminal arms.

Amino Acid Sequence↗
PubMed1993

Antigenic variants of Plasmodium chabaudi chabaudi AS and the effects of mosquito transmission.

Previous results, using a passive transfer assay, have shown that recrudescences of Plasmodium chabaudi chabaudi AS strain are antigenically different from the infecting parental population and also that the recrudescence appears to be a mix of antigenic types. This present study examines further these recrudescent populations using an indirect fluorescent antibody test on live, schizont-infected red blood cells. This analysis shows that ten clones derived from a recrudescence are all antigenically different from the parent population and that some are different from each other. The use of this method to examine the antigenic types of recrudescent clones after transmission through mosquitoes also demonstrates a resulting change in antigenicity. Such results showing a link between mosquito transmission and varying antigenicity may have important implications in terms of immunity and vaccine development.

Animals↗
PubMed1993

Protective CD4+ T-cell lines raised against Plasmodium chabaudi show characteristics of either Th1 or Th2 cells.

Splenic T-lymphocyte lines were established in vitro from Plasmodium chabaudi-infected NIH mice on days 16 and 20 of a primary infection, and from mice after two or three infections. Each line responded specifically to stimulation with a lysed soluble extract of P. chabaudi-infected erythrocytes (pRBC), and displayed a CD4+ (L3T4+) surface phenotype. Both the day 16 and 20 cell lines, when stimulated in vitro, secreted interleukin-2 (IL-2) and gamma-interferon (IFN-gamma), indicative of their belonging to the T helper 1 (Th1) CD4+ subset. In contrast, both lines derived from reinfected mice secreted interleukin-4 (IL-4) and provided helper activity in antibody production to P. chabaudi in vitro, and thereby had the characteristics of Th2 cells. All four T-cell lines provided significant protection to naïve mice infected with P. chabaudi. In immunocompromised mice, the day 16 T-cell line was as protective as in naïve mice whereas the cell line from mice infected twice required the additional transfer of mature naïve splenic B cells to provide protection comparable to that seen in the immunocompetent naïve recipients. The results establish that protective immunity to P. chabaudi may be associated with the induction of CD4+ T cells of either the Th1 or Th2 subset which confer protection against this malaria parasite by mechanisms independent of, and dependent upon, B-cell involvement, respectively.

Analysis of Variance↗