European best practice guidelines 14-16: inadequate response to epoetin.
Explore the source record for details and available documents.
Anemia↗
Biomedical subjects
C Jacobs
Publications and source records attributed to C Jacobs.
European best practice guidelines 17-18: adverse effects.
Explore the source record for details and available documents.
Anemia↗
Use of two-hybrid methodology for identifying proteins of interest in endocrinology.
During the last 10 years, much progress has been made in understanding signal transduction. However, the function of many newly identified proteins remains unknown. The protein/protein interactions have emerged as a major biochemical mechanism of signal transduction. They are of major interest to elucidate the role of a protein in one or another cellular process. The two-hybrid system is especially well designed for such investigation. Here we show that the contribution of this technique already is and will be essential in dissecting the molecular mechanism of transduction pathways in many cell types.
Animals↗
Bacterial cell division: a moveable feast.
Explore the source record for details and available documents.
Bacillus subtilis↗
Cell cycle-dependent polar localization of an essential bacterial histidine kinase that controls DNA replication and cell division.
The master CtrA response regulator functions in Caulobacter to repress replication initiation in different phases of the cell cycle. Here, we identify an essential histidine kinase, CckA, that is responsible for CtrA activation by phosphorylation. Although CckA is present throughout the cell cycle, it moves to a cell pole in S phase, and upon cell division it disperses. Removal of the membrane-spanning region of CckA results in loss of polar localization and cell death. We propose that polar CckA functions to activate CtrA just after the initiation of DNA replication, thereby preventing premature reinitiations of chromosome replication. Thus, dynamic changes in cellular location of critical signal proteins provide a novel mechanism for the control of the prokaryote cell cycle.
Bacterial Proteins↗
Long-term follow-up of living kidney donors: quality of life after donation.
The University of Minnesota has been a strong advocate of living donor kidney transplants. The benefits for living donor recipients have been well documented. The relative low risk of physical complications during donation has also been well documented. Less well understood is the psychosocial risk to donors. Most published reports have indicated an improved sense of well-being and a boost in self-esteem for living kidney donors. However, there have been some reports of depression and disrupted family relationships after donation, even suicide after a recipient's death. To determine the quality of life of our donors, we sent a questionnaire to 979 who had donated a kidney between August 1, 1984, and December 31, 1996. Of the 60% who responded, the vast majority had an excellent quality of life. As a group, they scored higher than the national norm on the SF-36, a standardized quality of life health questionnaire. However, 4% were dissatisfied and regretted the decision to donate. Further, 4% found the experience extremely stressful and 8% very stressful. We used multivariate analysis to identify risk factors for this poor psychosocial outcome and found that relatives other than first degree (odds ratio=3.5, P=0.06) and donors whose recipient died within 1 year of transplant (odds ratio=3.3, P=0.014) were more likely to say they would not donate again if it were possible. Further, donors who had perioperative complications (odds ratio=3.5, P=0.007) and female donors (odds ratio=1.8, P=0.1) were more likely to find the overall experience more stressful. Overall, the results of this study are overwhelmingly positive and have encouraged us to continue living donor kidney transplants.
Adolescent↗
Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma.
High-dose chemotherapy followed by autologous transplantation has been shown to improve response rates and survival in multiple myeloma and other malignancies. However, autografts frequently contain detectable tumor cells. Enrichment for stem cells using anti-CD34 antibodies has been shown to reduce autograft tumor contamination in phase I/II studies. To more definitively assess the safety and efficacy of CD34 selection, a phase III study was completed in 131 multiple myeloma patients randomized to receive an autologous transplant with either CD34-selected or unselected peripheral blood progenitor cells after myeloablative therapy. Tumor contamination in the autografts was assessed by a quantitative polymerase chain reaction detection assay using patient-specific, complementarity-determining region (CDR) Ig gene primers before and after CD34 selection. A median 3.1 log reduction in contaminating tumor cells was achieved in the CD34 selected product using the CEPRATE SC System (CellPro, Inc, Bothell, WA). Successful neutrophil engraftment was achieved in all patients by day 15 and no significant between-arm difference for time to platelet engraftment occurred in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. In conclusion, this phase III trial demonstrates that CD34-selection of peripheral blood progenitor cells significantly reduces tumor cell contamination yet provides safe and rapid hematologic recovery for patients receiving myeloablative therapy.
Adolescent↗
A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R) in patients with relapsed and refractory acute myeloid leukemia.
PURPOSE: The recombinant human interleukin-1 receptor (rhu IL-1R) is a soluble truncated form of the type 1 full-length membrane-bound receptor that binds IL-1 with identical affinity to that of the membrane form. As such, it may have clinical potential by sequestering IL-1, thereby preventing it from binding to its membrane-bound receptor and eliciting a biological effect. As IL-1 has been shown to regulate leukemic cell proliferation in an autocrine fashion, a phase I trial of rhu IL-1R was conducted in patients with relapsed and refractory acute myeloid leukemia (AML). METHODS: The study group comprised 11 patients who were sequentially treated on one of three dose levels, receiving a single intravenous (i.v.) bolus dose on day 1 followed by 13 days of daily subcutaneous (s.c.) injections with the option of an additional 14 days of treatment if a response of stable disease or better was achieved. Dose level 1 i.v. bolus 500 microg/m2, s.c. dose 250 microg/m2 per day (five patients); dose level 2 i.v. bolus 1000 microg/m2, s.c. dose 500 microg/m2 per day (three patients); dose level 3 i.v. bolus 2000 microg/m2, s.c. dose 1000 microg/m2 per day (three patients). Owing to limited drug availability, the study was designed to only examine these three dose levels. RESULTS: rhu IL-IR was well tolerated. There was no grade 3 or 4 non-hematological toxicity related to the study drug and the maximum tolerated dose was not reached. No IL-1R-blocking antibodies developed during the course of the study. Serum levels of IL-1beta, IL-6 and TNF were undetectable before, during and after rhu IL-IR administration. The terminal half-life after i.v. dosing was at least 7-12 h, and after s.c. dosing 2-4 days. Serum levels of rhu IL-1R up to 360- and 25-fold those of pretreatment levels were achieved after i.v. and s.c. dosing respectively. No patient had a complete, partial or minor response to treatment; four had stable disease and seven had progressive disease. CONCLUSIONS: rhu IL-1R therapy was safe but did not have any apparent antileukemic effect at the doses administered.
Aged↗
Identifying insanity acquittals: is it any easier?
Following the highly publicized insanity acquittal of John Hinckley in 1982, legislators throughout the country attempted to reform the insanity defense. At the time, policy makers had virtually no empirical evidence with which to guide their reforms. The focus of this research is to determine if more informed policy-making would be possible today? Results show that more states are able to identify cases involving an insanity acquittal than during the 1980's and provide annual data on the number of rate of insanity acquittals. The data collected by many of the states have significant limitation.
Data Collection↗
Collection of peripheral blood progenitor cells (PBPC) based on a rising WBC and platelet count significantly increases the number of CD34+ cells.
The kinetics of mobilization and optimal timing of peripheral blood progenitor cell (PBPC) collection were evaluated in 190 patients with multiple myeloma undergoing stem cell harvest after mobilization with cyclophosphamide, prednisone and G-CSF. There was a strong correlation between the WBC count and the number of CD34+ cells circulating in peripheral blood (r = 0.875). Initiating leukapheresis based on rising WBC and platelet counts rather than on a fixed day increased the mean number of CD34+ cells 115% (9.7 to 20.9 x 10(6) CD34+ cells/kg; P = 0.010) for the total of all leukaphereses and 59% for the total of all CD34-selected products (5.1 to 8.1 x 10(6) CD34+ cells/kg; P = 0.011). Although the yield and purity of the CD34-selected product were not significantly affected (P > or = 0.071), the percentage of patients with concentrations of CD34+ cells in the initial leukapheresis of > 1% increased from 47% to 70% (P = 0.004). The mean purity of the selected product was related to the starting percentage: 48.9% if < 1% and 81.5% if > or = 1% (P < 0.001). Collection of stem cells based on rising WBC and platelet counts significantly increased the number of CD34+ cells in leukaphereses and CD34-selected products in comparison with collection on a fixed day.
Adult↗
Normalization of haemoglobin: why not?
It has been suggested that normalization of haemoglobin with epoetin in anaemic chronic renal failure (CRF) patients might result in even greater benefits than those currently achieved with partial haemoglobin correction. Four prospective randomized trials recently examined this hypothesis. The Scandinavian Multicentre Trial, which was completed in February 1998, included 416 haemodialysis, continuous ambulatory peritoneal dialysis and pre-dialysis patients. Preliminary analysis of the data found no differences with respect to safety between patients treated to achieve subnormal haemoglobin (9.0-12.0 g/dl) and those in whom haemoglobin was normalized (13.5-16.0 g/dl). The Canadian Multicentre Trial included 159 haemodialysis patients with asymptomatic left ventricular (LV) dysfunction. In patients with a normal LV cavity volume at enrolment, the change in LV cavity volume at 48 weeks was significantly greater in the control group (target haemoglobin 9.5-10.5 g/dl) than in the intervention group (target haemoglobin 13.0-14.0 g/dl). The Normal Hematocrit Cardiac Trial in the US included 1233 haemodialysis patients with clinically evident ischaemic heart disease or congestive heart failure. The trial was stopped in 1996 after an interim analysis showed increased mortality in the intervention group (target haematocrit 42%) compared with the control group (target haematocrit 30%). The higher haematocrit values themselves, however, did not appear to be responsible for the differences in mortality, as the mortality rates within each group decreased with increasing haematocrit. Nonetheless, until evidence is available from other trials demonstrating a benefit of normalizing haemoglobin, it has been recommended that a target haematocrit value of 42% be avoided in haemodialysis patients with clinically evident ischaemic heart disease or congestive heart failure. Further studies are also required to determine whether increasing haemoglobin to normal may prove to be beneficial in other patient groups. The Spanish Quality of Life Study of 134 haemodialysis patients found a significant improvement in all quality-of-life parameters when haemoglobin was increased to a mean of 12.5 g/dl. The investigators suggested that in patients without severe co-morbidity, the target haemoglobin should be as close to normal as possible.
Hematocrit↗
Severe Contractures of the Proximal Interphalangeal Joint in Dupuytren's Disease:Value of Capsuloligamentous Release.
A retrospective review of severe flexion contractures (60 degrees or more), involving 51 proximal interphalangeal joints in 40 patients with Dupuytren's disease, was performed. Thirty-two joints underwent aponeurectomy alone, 19 joints additional capsuloligamentous release. Mean follow-up was 12 months. No statistically significant difference was seen in the percentage of contracture correction in the capsulotomy group compared with the noncapsulotomy group.
Journal Article↗
Medication nonadherence and its relation to financial restriction.
The question of patient nonadherence has always been an important factor in determining candidate suitability for organ transplantation. Data that explore the association of financial problems and posttransplant medication nonadherence are limited. Findings suggest that medication nonadherence was more likely to occur when recipients did not have insurance coverage and had to rely on Medicaid or indigent drug programs. Our center developed a formalized program within the outpatient pharmacy, including a full-time medication counselor who helped recipients secure resources to pay for pre- and posttransplant medications. To determine whether the availability of posttransplant medications could reduce medication nonadherence, we conducted a survey with 50 consecutive liver transplant recipients in the outpatient clinic. Nonadherence rates were significantly reduced from 25% to 10% (P < .01) compared with recipients who had been transplanted before the development of our drug program. These results suggest that optimum medication adherence can be obtained when recipients are provided guidance in securing their necessary medications without financial restriction.
Drug Costs↗
[Chronic renal insufficiency. A permanent public health problem].
Chronic renal insufficiency raises an ever-increasing public-health problem due to its permanent growth among the general population and the escalating cost of renal replacement therapies. By the end of 1995 there were close to 33,700 patients with end-stage renal failure maintained alive with renal replacement methods in France. About 11,200 had a functioning kidney graft, whereas 22,500 were treated with various dialysis techniques, in and out-of-center hemodialysis and peritoneal dialysis. An optimal health policy should contribute both to prevent renal insufficiency and offer each patient his/her best specific mode of treatment at the lowest cost for the community. Renal transplantation should be much more widely promoted and utilized through measures aiming at reducing the too high refusal rates of organ donation in subjects with brain-death. Promotion and extension of out-of-center dialysis techniques are also necessary. Design of reliable epidemiological studies dealing not only with end-stage renal failure patients but with the early stage and time-course of renal insufficiency is also mandatory. A deeper investigation in the area of renal-risk factors and a qualified follow-up of patients with mild/moderate renal insufficiency are essential to avoid or delay an evolution towards end-stage renal failure. Prevention of renal fibrosis has a central role in such a long-term public health-policy.
France↗
Lymphomas of the head and neck.
Lymphomas of the head and neck arise in Waldeyer's ring, the salivary glands, nasal cavity, paranasal sinuses, thyroid gland, and orbit. Though anatomically in close proximity, lymphomas arising in these sites have distinct clinical characteristics. Factors that appear to influence the pattern of disease include concurrent conditions, such as Sjögren's syndrome, and geographic factors, particularly with regard to nasal lymphomas. The treatment and prognosis of patients with head and neck lymphoma depends on the histologic grade of disease and extent of involvement at time of presentation. Most lymphomas are of intermediate-grade histology and early stage at presentation. A thorough understanding of clinical disease patterns and treatment options will allow the optimum management of these patients.
Head and Neck Neoplasms↗
Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer.
Epidemiological studies have shown an increased risk of breast cancer in obligate ataxia telangiectasia (A-T) heterozygotes. We analyzed 100 samples from young breast cancer patients for mutations in ataxia-telangiectasia mutated (ATM), the gene responsible for the autosomal recessive condition, A-T, to determine whether A-T heterozygosity predisposes such individuals to develop breast cancer. These patients were selected from families with a moderate or absent family history of breast cancer and included a subset of 16 radiosensitive patients. Forty-four germline sequence variants were detected by fluorescent chemical cleavage of mismatch of RT-PCR products. These included seven rare variants found in nine patients (three described for the first time), but no truncating mutations. Although three variants were detected in the radiosensitive subset, this was not statistically significant compared to the nonradiosensitive group. One variant, G2765S, is likely to be a missense mutation, but the other six variants probably represent rare polymorphisms. However, five of the seven rare germline variants detected showed loss of heterozygosity of the wild-type ATM allele for one or more markers close to the ATM locus in matched tumor DNA. This high rate of somatic inactivation of ATM may indicate either that these rare variants play a role in breast cancer development or alternatively that a neighboring tumor suppressor gene is important for tumorigenesis. We found germline truncating ATM mutations to be rare in these young breast cancer patients and therefore they are unlikely to play a role in the etiology of their disease. Genes Chromosomes Cancer 26:286-294, 1999.
Adult↗
[Pharmacokinetics of an unfractionated heparin (Liquemin) in the dog after intravenous and subcutaneous application based on heparin activity].
In this study pharmacokinetic data for the unfractionated heparin Liquemin were obtained after intravenous and subcutaneous application. Each dosage was examined in 5 healthy, adult Beagle dogs. After intravenous application of 25, 50 and 100 I.U./kg body weight heparin plasma activity of 0.65 +/- 0.15 I.U./ml (mean +/- s), 0.91 +/- 0.10 I.U./ml and 1.94 +/- 0.22 I.U./ml was measured. Subcutaneous applications of 250, 500 or 750 I.U./kg revealed maximum plasma heparin activities of 0.25 +/- 0.10, 0.60 +/- 0.15 and 1.29 +/- 0.24 I.U./ml. The maximum heparin activity in the plasma was observed after 3.8 +/- 1.1 (250 und 500 I.E./kg) or 4.0 +/- 1.0 hours (750 I.E./kg), respectively. Intravenously applicated heparin has a short terminal half-life time (t50) between 22 and 44 minutes. The t50 after subcutaneous application of heparin was distinctly longer. After 250, 500 or 750 I.U./kg the t50 was 3.7 +/- 2.4, 3.5 +/- 1.2 or 5.3 +/- 2.4 hours. Corresponding to this result a lower total clearance (Cltot) was found with increasing doses. Especially the Cltot after subcutaneous injection decreased from 2.08 +/- 0.73 ml/min/kg (250 I.E./kg) to 0.83 +/- 0.27 ml/min/kg (750 I.E./kg). The volume of distribution of heparin corresponded approximately to the plasma volume. The total bioavailability of subcutaneously administered UFH was 53-100% depending on the dosage.
Animals↗
Simulating patient care.
In a pioneering program, medical students are introduced to the unique challenges of taking a medical history and examining patients who cannot speak because of severe developmental disabilities. Contact with patient simulators helps the medical students develop the interpersonal skills needed to elicit vital information directly from nonverbal patients.
Clinical Competence↗