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Biomedical subjects

K Wise

Publications and source records attributed to K Wise.

At least 19 recordsLinked to original sources

The efficacy of prophylactic outpatient antibiotics for the prevention of neutropenic fever associated with high-dose etoposide (VP-16) for stem cell mobilization.

High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program.

Ambulatory Care↗

Prospective evaluation of an outpatient heart failure management program.

BACKGROUND: Although considerable effort has been devoted to the follow-up of hospitalized patients, the effectiveness and process of heart failure outpatient management have not been well demonstrated. METHODS AND RESULTS: All new patients referred to the program from April 1997 to September 1998 were followed and managed by comprehensive strategies including preemptive hospitalization. Quality of life (QOL) and patients' self-care adherence behaviors were measured at baseline, 3 months, and 6 months. Clinical outcomes were compared for the 6 months before and 6 months after referral. A total of 108 patients were recruited. Patients' self-care knowledge score was improved over time (difference score = 0.9, P <.01). The proportion of patients weighing themselves daily increased by 24% (P =.02). The proportion of patients with New York Heart Association (NYHA) class III to IV was 67.6% at baseline and 49.1% at 6 months (P =.01). Compared with 6 months before referral, the program intervention was accompanied by a 52% reduction in the risk of hospitalization for cardiovascular causes (56.1% v 27.2%, P <.001) and a 72% reduction in emergency room visits (53.6% v 14.5%, P <.01). The total hospital admissions for cardiovascular causes decreased by 59% from 94 to 39; the total emergency room visits decreased by 77% from 83 to 19. The patients' QOL was improved over time with a change score of 11.2 (P <.001) at 3 months and 10.7 (P <.001) at 6 months. CONCLUSION: Our study shows the effectiveness of this heart failure outpatient management program.

Adult↗

Idiopathic polypoidal choroidal vasculopathy and sickle cell retinopathy.

PURPOSE: To report a patient who had concomitant idiopathic polypoidal choroidal vasculopathy and sickle cell retinopathy. METHOD: Case report. A 46-year-old black woman presented with sudden onset of "blurring" in the left eye. Her ocular history was unremarkable, and her medical history was relevant for sickle cell disease with yearly episodes of sickle cell crises. RESULTS: Both eyes had evidence of idiopathic polypoidal choroidal vasculopathy and peripheral retinal neovascularization secondary to sickle cell disease. The left eye had hemorrhagic retinal pigment epithelial detachments secondary to idiopathic polypoidal choroidal vasculopathy. CONCLUSION: We present this case as an example of concomitant sickle cell retinopathy and idiopathic polypoidal choroidal vasculopathy. We are unaware of previous reports with these findings.

Anemia, Sickle Cell↗

Comparative responsiveness of Short-Form 12 and Minnesota Living With Heart Failure Questionnaire in patients with heart failure.

BACKGROUND: The Short-Form 12 (SF-12) and Living With Heart Failure Questionnaire (LHFQ) are commonly used to measure quality of life (QOL) in heart failure outcomes research. Their comparative responsiveness, however, has not been documented. METHODS AND RESULTS: A prospective cohort study was conducted among patients attending a university-based heart failure clinic between April 1997 and September 1998. All patients received comprehensive heart failure care management. QOL of patients was assessed by the SF-12 and LHFQ at baseline and 3 months. Of 87 patients completing follow-up, the mean change score was 10.1 for the LHFQ and 5.8 for the SF-12 (both Ps < .001). The change scores of the instruments were correlated (r = 0.61; P < .001). The SF-12 had a greater ability than the LHFQ to statistically detect change in physical health but was less sensitive to changes in mental health. The LHFQ performed better than the SF-12 in the ability to distinguish the differences in perceived global health transition. CONCLUSION: The LHFQ is more responsive than the SF-12 to changes in QOL. The SF-12 should not be used alone to measure the changes in QOL of patients with heart failure.

Adult↗

Autologous peripheral blood progenitor cell transplantation for transformed diffuse large-cell lymphoma.

The outcome of patients with transformed diffuse large-cell lymphoma is poor. High-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation is the treatment of choice for patients with relapsed nontransformed diffuse large-cell lymphoma. The role of transplantation for transformed lymphoma is poorly studied. We retrospectively reviewed 118 consecutive diffuse large-cell lymphoma patients undergoing autologous PBPC transplantation from 1994 through 1999 and compared 18 transformed diffuse large-cell lymphoma patients with 100 nontransformed patients. The transformed patients were more likely to be older (median age, 52 years vs. 45 years, P = 0.03), had a longer time from diagnosis to transplant (median, 35 months vs. 10 months; P < 0.0001), were more likely to have bone marrow involvement at diagnosis (61% vs. 15%, P = 0.0001), and were more likely to have had 2 or more courses of prior chemotherapy (94% vs. 71%, P = 0.04) than were nontransformed patients. Ninety-nine percent of patients received high-dose busulfan/cyclophosphamide/etoposide as the transplant preparative regimen. Event-free survival and overall survival were similar in the two treatment groups. Four-year overall survival was 53% in the nontransformed group versus 61% in the transformed group; 4-year event-free survival was 37% in the nontransformed group versus 38% in the transformed group. We concluded that autologous PBPC transplantation is a viable and potentially effective treatment option for patients who have transformed diffuse large-cell lymphoma.

Adolescent↗

Factors influencing knowledge of and adherence to self-care among patients with heart failure.

BACKGROUND: Patient education has been shown to be a key component in comprehensive heart failure management. Few data, however, are available regarding patients' knowledge of and adherence to self-care recommendations for the disease. OBJECTIVES: To assess the knowledge level of and adherence to self-care among patients with heart failure and to determine associated factors. METHODS: We conducted a needs-assessment survey among new patients visiting a heart failure clinic from April 1997 through June 1998. Multiple linear regression analysis was used to assess the factors predictive of patients' knowledge level and adherence behaviors. RESULTS: Of the 113 patients surveyed, 77% were referred by cardiologists and 60% had New York Heart Association class III or IV status. Two thirds of the patients reported receiving information or advice about self-care from health care providers. When asked how much they knew about congestive heart failure, however, 37% said "a little or nothing," 49% said "some," and only 14% said "a lot." Approximately 40% of the patients did not recognize the importance of weighing themselves daily and 27% weighed themselves twice a month or less often. Although 80% of the patients knew they should limit their salt intake, only one third always avoided salty foods. Additionally, 25% of the patients did not appreciate the risk of alcohol use and 36% believed they should drink a lot of fluids. The multiple linear regression analysis indicated that a higher knowledge score was associated with being married, prior hospitalization, and having received both advice and information about self-care from physicians or nurses. A poor adherence behavior score was associated with being unmarried, lower perceived self-efficacy, a lack of knowledge about self-care, and no prior hospitalization. CONCLUSIONS: We observed a gap between patients receiving and absorbing or retaining information on self-care for congestive heart failure supplied by health care providers. Self-care education needs to be directed to outpatients in addition to inpatients.

Adult↗

LDH elevation after autologous stem cell transplantation.

We have anecdotally noted that serum LDH values rise after the infusion of autologous peripheral blood progenitor cells (PBPCs), presumably the result of cellular lysis. To further study this issue, we retrospectively reviewed 203 consecutive patients undergoing autologous PBPC transplant from August 1996 to December 1997. 194 patients were evaluable, having documented LDH values on day -1 to day +5 post-transplant. All patients received cytokine mobilization for PBPC collection, and 99% received a chemotherapy-only preparative regimen. 99% of patients had a rise in serum LDH after PBPC infusion. 76% had a normal LDH prior to PBPC infusion that became abnormally high after infusion; 22% began with an abnormally high value that became higher with the infusion of PBPCs. The LDH rose at least 50% in 91% of patients. 92% of the patients had their peak LDH value occur on day +1 post-transplant. The total dose of CD34+ cells infused negatively correlated with peak percentage change of LDH (P = 0.0007). This result was initially perplexing, as we believed that a higher number of infused cells would correlate with a higher LDH value as a result of in vivo cellular lysis. However, the total number of CD34+ cells also negatively correlated with the number of phereses required to collect our threshold of 2.0 x 10(6) CD34+ cells/kg (P = 0.0001). After adjusting for CD34+ cell dose, we found that the number of phereses correlated highly with a peak percentage of change of LDH (P = 0.001). We conclude that the serum LDH increases universally after autologous PBPC infusion, peaking on day +1. We believe that this rise in serum LDH is a result of cell lysis that occurs ex vivo, and correlates with the number of pheresis procedures required to collect an adequate number of CD34+ cells. This may be a result of increasing red blood cell contamination with more phereses, and resultant RBC hemolysis.

Acyclovir↗

Meeting the expectations of chronic tinnitus patients: comparison of a structured group therapy program for tinnitus management with a problem-solving group.

Two different group treatments were evaluated in 144 in-patients suffering from impairment due to chronic tinnitus. A tinnitus management therapy (TMT) was developed using principles of cognitive-behavioral therapy and compared with problem solving group therapy. Self-ratings were used to evaluate the help patients found in dealing with life problems and tinnitus as well as the degree to which they felt they were being properly treated and taken seriously. Patients showed significantly more satisfaction with the TMT group and evaluated the help they found in coping with tinnitus and life problems significantly higher. Thus, in the light of unsatisfactory medical solutions and the poor acceptance of some psychological treatments for tinnitus, TMT appears to be an acceptable and helpful treatment program.

Adaptation, Psychological↗

A randomized study of multi-day infusion of autologous peripheral blood progenitor cells.

Peripheral blood progenitor cells (PBPC) are increasingly used as the source of stem cells in both the autologous and allogeneic settings. Based on previous early non-randomized studies reporting enhanced engraftment following fractionated autologous PBPC infusion, some centers and study groups infuse PBPC over 3 days. To study the possible benefit of multiple day PBPC infusion, 60 patients receiving high-dose chemotherapy and autologous progenitor cell transplantation (ABMT) were randomized to receive their PBPC divided over 1, 2 or 3 days. Stem cells were mobilized with G-CSF 5 microg/kg for 7 days and PBPC were collected on days 5-7. Patients received daily G-CSF 5 microg/kg i.v. over 30 min beginning 4 h after the infusion of the first aliquot of PBPCs. Toxicity was similar for the 1, 2 and 3 day infusion groups. The median time to achieve 500 neutrophils/mm3 was 10, 11 and 11 days in the groups receiving PBPCs over 1, 2 or 3 days, respectively. The median time to achieve a platelet count of 20 x 10(9)/l was 11 days for the group receiving their cells as a single infusion and 12 days in the other two groups. We conclude that expanding PBPC infusion over 2 or 3 days does not enhance engraftment or reduce toxicity.

Adolescent↗

Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial.

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.

Breast Neoplasms↗

Variables associated with the platelet count 6 weeks after autologous peripheral blood progenitor cell transplantation.

While abundant data exist documenting variables associated with early platelet engraftment after autologous PBPC transplantation, data concerning later sustained platelet engraftment is sparse. We retrospectively examined a series of 80 patients undergoing autologous PBPC transplantation with respect to their platelet count 6 weeks after transplant. Underlying diagnoses included breast cancer (n = 33), non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 9), and other hematologic malignancies (n = 6). Patients received G-CSF for PBPC mobilization and collected a target threshold number of 2.0 x 10(6) CD34+ cells per kilogram. A univariate analysis revealed that a diagnosis of breast cancer, fewer courses of prior chemotherapy, younger age and complete remission were associated with a higher 6-week platelet count. Additionally, the ability to collect the threshold number of CD34+ with fewer sessions of leukapheresis was also associated with a higher 6-week platelet count. The platelet count and the white blood cell count at the initiation of PBPC collection was also associated with a higher 6-week platelet count. A multivariate analysis revealed a higher platelet count on the first day of pheresis, fewer phereses required to collect 2 x 10(6) CD34+ cells per kilogram, and a diagnosis of breast cancer were all associated with a higher 6-week post-transplant platelet count. Seven patients failed to reach a 6-week platelet count of 30 x 10(9)/l and an additional five patients had a platelet count of 30-50 x 10(9)/l. We conclude that underlying clinical characteristics, as well as hematologic variables at the time of PBPC collection, influence later, sustained platelet engraftment. A percentage of patients have poor sustained platelet engraftment and may be candidates for new cytokines that specifically target megakaryocyte growth and development.

Adult↗

Unique Salmonella choleraesuis surface protein affecting invasiveness. Possible inv related sequence.

TnphoA mutagenesis of a Salmonella choleraesuis isolate recovered from septicemic infection of feeder pigs resulted in 56 PhoA+ KnR StrR mutants. Thirty-five mutants exhibited reduced levels of invasion in the Hep-2 cell model and were examined by SDS-PAGE Western Blot analysis using an anti-alkaline phosphatase antibody to visualize the insertion gene products. A mutant which produced a gene fusion product of 95 kDa and exhibited > 90% reduction in invasion was subcloned. A 10 Kb BamHI fragment of the chromosome containing the phoA insert was detected by hybridization and cloned into a pGEM vector. The resulting 1657 base sequence contained a 1104 bp ORF with two short regions of homology with S. typhimurium invF and invG. one region of homology with lcrD of Yersinia pseudotuberculosis but contained largely unique sequences not contained in Gene Bank. The full length sequence was not obtained as there was no stop codon detected. The % G+C was 44%, considerably lower than that of the Salmonella chromosome, but compatible with the proposed Yersinia origin of the inv genes. The NH2 387 a.a. sequence includes 5 transmembrane regions, resembling the model derived from the hydrophobicity plot of S. typhimurium InvA.

Antigens, Surface↗

G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10, and 16 micrograms/kg/day.

G-CSF is routinely administered after autologous bone marrow or peripheral blood progenitor cell transplantation to enhance neutrophil engraftment. However, many different doses of G-CSF have been described with no clear consensus on the most cost-effective dose. We performed a prospective randomized trial examining the efficacy of three different doses of G-CSF post-autologous transplant (5, 10, or 16 micrograms/kg/day). Fifty-seven consecutive patients with breast cancer (n = 30), non-Hodgkin's lymphoma (n = 16), Hodgkin's disease (n = 6), multiple myeloma (n = 2), acute leukemia (n = 2), and testicular cancer (n = 1) were randomized, with 19 patients enrolled in each of the three treatment groups. All patients underwent a high-dose chemotherapy preparative regimen and received an autologous peripheral blood progenitor cell (PBPC) transplant (without bone marrow), with G-CSF beginning on day 0. There was no difference in time to neutrophil engraftment among the three treatment groups (mean 10.2 to 10.8 days). There is a trend towards earlier platelet engraftment in the patient group receiving 5 microgram/kg/day of G-CSF. The total cost of G-CSF by dose group was $2900, $4400, and $6500 per patient. We conclude that there was no advantage to the use of higher doses of G-CSF after autologous transplantation, and that lower doses are associated with lower costs.

Adult↗

Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat.

The cellular generation and spatial distribution of gamma frequency (40-100 Hz) activity was examined in the hippocampus of the awake rat. Field potentials and unit activity were recorded by multiple site silicon probes (5- and 16-site shanks) and wire electrode arrays. Gamma waves were highly coherent along the long axis of the dentate hilus, but average coherence decreased rapidly in the CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in coherence values between the dentate and CA1 gamma waves. Current source density analysis revealed large sinks and sources in the dentate gyrus with spatial distribution similar to the dipoles evoked by stimulation of the perforant path. The frequency changes of gamma and theta waves positively correlated (40-100 Hz and 5-10 Hz, respectively). Putative interneurons in the dentate gyrus discharged at gamma frequency and were phase-locked to the ascending part of the gamma waves recorded from the hilus. Following bilateral lesion of the entorhinal cortex the power and frequency of hilar gamma activity significantly decreased or disappeared. Instead, a large amplitude but slower gamma pattern (25-50 Hz) emerged in the CA3-CA1 network. We suggest that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus. We also hypothesize that under physiological conditions the hilar gamma oscillation may be entrained by the entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.

Animals↗

Dose-related efficacy and bleeding complications of double-chain tissue plasminogen activator in acute myocardial infarction. The Wellcome Tissue Plasminogen Activator Study Group.

Although the efficacy of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction has been demonstrated, little formal dose-ranging information is available. This study examined the use of duteplase, the double-chain rt-PA subsequently used in the Third International Study of Infarct Survival, in a multicenter trial of 267 patients with evolving acute myocardial infarction assigned to receive 1 of 6 weight-adjusted doses. The primary end point was infarct vessel patency after 90 minutes of drug infusion. Patency was defined as Thrombolysis in Myocardial Infarction trial grade 2 or 3 perfusion, and was determined by an independent core laboratory masked to treatment assignment. Patency was present in 48% of patients receiving the lowest dose range and 78% of those receiving the highest, with an association between thrombolytic dose and patency (p = 0.009). The frequency of serious bleeding complications also correlated with the total dose of rt-PA infused (p = 0.003). Bleeding complications were primarily related to instrumentation; blood loss requiring transfusion or otherwise deemed clinically significant occurred in 12% of patients (central nervous system hemorrhage occurred in 1.1%). Thus, higher doses of rt-PA are associated both with increased efficacy and increased risk of serious bleeding complications. Weight-adjusted dosing may provide an optimal risk-benefit ratio for thrombolysis during acute myocardial infarction.

Adult↗

High-frequency network oscillation in the hippocampus.

Pyramidal cells in the CA1 hippocampal region displayed transient network oscillations (200 hertz) during behavioral immobility, consummatory behaviors, and slow-wave sleep. Simultaneous, multisite recordings revealed temporal and spatial coherence of neuronal activity during population oscillations. Participating pyramidal cells discharged at a rate lower than the frequency of the population oscillation, and their action potentials were phase locked to the negative phase of the simultaneously recorded oscillatory field potentials. In contrast, interneurons discharged at population frequency during the field oscillations. Thus, synchronous output of cooperating CA1 pyramidal cells may serve to induce synaptic enhancement in target structures of the hippocampus.

Action Potentials↗