bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defensive practice among psychiatrists: a questionnaire survey
Authors: Passmore K , Leung W-C 
Published: December 2002

Abstract

Objective
There has been little research on the prevalence of defensive practice within hospital settings. The aim of this report was to examine the extent of defensiveness among psychiatrists and to examine the relationship between defensiveness and seniority, as well as the effect of previous experiences on the level of defensiveness.

Design
A postal questionnaire survey on defensive practice.

Setting
Northern Region of England.

Subjects
154 psychiatrists in the region.

Results
96 responses were received from 48 equivalent consultants, 18 specialist registrars, and 23 equivalent senior house officers. Overall, 75% of those who replied had taken defensive actions within the past month. In particular, 21% had admitted patients overcautiously and 29% had placed patients on higher levels of observations. Junior psychiatrists were particularly prone to practise defensively. Important contributing factors included previous experience of complaints (against colleague or self), critical incidents, and legal claims.

Conclusion
Almost three quarters of the psychiatrists who responded had practised defensively within the past month. The higher propensity of junior trainees to practise defensively may be attributable to their lack of confidence and experience. Experience of complaints (colleague or self) and critical incidents were important factors for defensive practice. Better and more structured training might reduce the high level of defensive practice and the way complaints and investigations are handled should be improved to maintain a truly “no blame” environment conducive to learning from past experience.
Anxiety and depression in an older research population and their impact on clinical outcomes in a randomised controlled trial
Authors: Allsup S J , Gosney M A 
Published: December 2002

Abstract

Introduction
Anxiety and depression are common in older people living in the community. The aim of the study was to investigate their impact on clinical outcomes during a randomised controlled trial investigating the cost benefits of influenza vaccination in fit and healthy, independent living 65–74 year olds.

Subjects and methods
A total of 729 people were recruited. Participants completed the hospital anxiety and depression scale (HADS) and EuroQol EQ-5D quality of life questionnaire immediately before receiving vaccination and every two months for the next six months after this. Side effects three days after vaccination and Barthel score at baseline were also recorded.

Results
At baseline the prevalence of “definite” anxiety in this sample (HADS score ≥11) was 4% and 1.2% of individuals had definite depression (HADS score ≥11). Individuals with anxiety or depression (HADS score ≥8) were more likely to complain of systemic side effects after vaccination and have a lower Barthel index score (p&lt;0.001). Quality of life as measured by the EQ-5D visual analogue scale was reduced (p&lt;0.001) at all time periods in those individuals with both anxiety and depression (HADS score ≥8 on both scales).

Conclusion
Although the prevalence of anxiety and depression in this sample was low, people with anxiety or depression were more likely to suffer from perceived side effects after influenza vaccine and have a lower Barthel and EQ-5D visual analogue score. In future studies the effect of anxiety and depression on older participants should be remembered and care taken to ensure that they do not affect results more than the intervention under study.
James Lind’s Treatise of the Scurvy (1753)
Authors: Bartholomew M 
Published: December 2002

Abstract
Lind is revered as the first doctor to conduct systematic clinical trials of potential cures for scurvy—trials in which oranges and lemons came out as decisive winners. The following paper argues that our modern understanding of scurvy and vitamin C has hindered our understanding of Lind’s own conception of his work and of the place within it of his clinical trials. Lind conceived of scurvy not as a disease of dietary deficiency, but of faulty digestion. In the full context of his Treatise of the Scurvy, and of his own medical practice, the seeming decisiveness of the trials fades, to be replaced by a sense of Lind’s bafflement at the nature of the disease to which he had devoted his career.
High-dose cyclophosphamide with autologous lymphocyte–depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia
Authors: Huhn Richard D. , Fogarty Patrick F. , Nakamura Ryotaro , Read Elizabeth J. , Leitman Susan F. , Rick Margaret E. , Kimball Janice , Greene Adeira , Hansmann Kristin , Gratwohl Alois , Young Neal , Barrett A. John , Dunbar Cynthia E. 
Published: December 2002

Abstract
Patients with refractory chronic autoimmune thrombocytopenia (AITP) have a significant risk of morbidity and mortality related to hemorrhage. High-dose (HD) cytotoxic therapy may produce remissions but entails risks related to myelosuppression. Hematopoietic stem cell support with lymphocyte-depleted grafts may accelerate hematologic recovery and concomitantly reduce repopulation by autoreactive immunocytes. Fourteen patients with chronic AITP, in whom multiple prior therapies including corticosteroids, splenectomy, intravenous immunoglobulin, and various cytotoxic or immunomodulatory regimens had failed, were treated with HD cyclophosphamide (50 mg/kg/d) and autologous granulocyte colony-stimulating factor (G-CSF)–mobilized leukocytes depleted of lymphocytes by immunomagnetic CD34+selection. There were no significant adverse events related to G-CSF, intravenous device insertion, or leukapheresis. Treatment-related complications included transient hemorrhagic cystitis (1 patient), vaginal bleeding (2 patients), gastrointestinal bleeding (1 patient), epistaxis (1 patient), and antibiotic-responsive febrile neutropenia (all patients). The mean time to absolute neutrophil count (ANC) more than 500/mm3 was 9 ± 0.6 days. Eight patients experienced antibiotic-responsive gram-positive bacteremia. A median of 2 platelet transfusions was required for stem cell mobilization, intravenous catheter insertion, and apheresis and a median of 9 platelet transfusions was required during hematopoietic recovery. Six patients obtained durable complete responses (platelet counts &gt; 100 000/mm3 without other therapy) with maximum follow-up of 42 months. Two additional patients obtained durable partial responses (platelet counts significantly increased over baseline with reduced medication requirements and cessation of bleeding complications). This therapeutic approach is feasible for patients with severe chronic AITP, a substantial proportion of whom may obtain durable remissions. Larger controlled trials are recommended.
Broad-spectrum caspase inhibition paradoxically augments cell death in TNF-α–stimulated neutrophils
Authors: Liu Chien-Ying , Takemasa Akihiro , Liles W. Conrad , Goodman Richard B. , Jonas Mechthild , Rosen Henry , Chi Emil , Winn Robert K. , Harlan John M. , Chuang Peter I. 
Published: December 2002

AbstractIt is increasingly clear that there are caspase-dependent and -independent mechanisms for the execution of cell death and that the utilization of these mechanisms is stimulus- and cell type–dependent. Intriguingly, broad-spectrum caspase inhibition enhances death receptor agonist-induced cell death in a few transformed cell lines. Endogenously produced oxidants are causally linked to necroticlike cell death in these instances. We report here that broad-spectrum caspase inhibitors effectively attenuated apoptosis induced in human neutrophils by incubation with agonistic anti-Fas antibody or by coincubation with tumor necrosis factor-α (TNF-α) and cycloheximide ex vivo. In contrast, the same caspase inhibitors could augment cell death upon stimulation by TNF-α alone during the 6-hour time course examined. Caspase inhibitor–sensitized, TNF-α–stimulated, dying neutrophils exhibit apoptoticlike and necroticlike features. This occurred without apparent alteration in nuclear factor–κB (NF-κB) activation. Nevertheless, intracellular oxidant production was enhanced and sustained in caspase inhibitor-sensitized, TNF-α–stimulated neutrophils obtained from healthy subjects. However, despite reduced or absent intracellular oxidant production following TNF-α stimulation, cell death was also augmented in neutrophils isolated from patients with chronic granulomatous disease incubated with a caspase inhibitor and TNF-α. These results demonstrate that, in human neutrophils, TNF-α induces a caspase-independent but protein synthesis–dependent cell death signal. Furthermore, they suggest that TNF-α activates a caspase-dependent pathway that negatively regulates reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.
Reversibility of CD34 expression on human hematopoietic stem cells that retain the capacity for secondary reconstitution
Authors: Dao Mo A. , Arevalo Jesusa , Nolta Jan A. 
Published: December 2002

AbstractThe cell surface protein CD34 is frequently used as a marker for positive selection of human hematopoietic stem/progenitor cells in research and in transplantation. However, populations of reconstituting human and murine stem cells that lack cell surface CD34 protein have been identified. In the current studies, we demonstrate that CD34 expression is reversible on human hematopoietic stem/progenitor cells. We identified and functionally characterized a population of human CD45+/CD34− cells that was recovered from the bone marrow of immunodeficient beige/nude/xid (bnx) mice 8 to 12 months after transplantation of highly purified human bone marrow–derived CD34+/CD38− stem/progenitor cells. The human CD45+ cells were devoid of CD34 protein and mRNA when isolated from the mice. However, significantly higher numbers of human colony-forming units and long-term culture-initiating cells per engrafted human CD45+ cell were recovered from the marrow of bnx mice than from the marrow of human stem cell–engrafted nonobese diabetic/severe combined immunodeficient mice, where 24% of the human graft maintained CD34 expression. In addition to their capacity for extensive in vitro generative capacity, the human CD45+/CD34− cells recovered from thebnx bone marrow were determined to have secondary reconstitution capacity and to produce CD34+ progeny following retransplantation. These studies demonstrate that the human CD34+ population can act as a reservoir for generation of CD34− cells. In the current studies we demonstrate that human CD34+/CD38− cells can generate CD45+/CD34− progeny in a long-term xenograft model and that those CD45+/CD34− cells can regenerate CD34+ progeny following secondary transplantation. Therefore, expression of CD34 can be reversible on reconstituting human hematopoietic stem cells.
T lymphocytes constitutively produce an interferonlike cytokine limitin characterized as a heat- and acid-stable and heparin-binding glycoprotein
Authors: Oritani Kenji , Hirota Seiichi , Nakagawa Taishirou , Takahashi Isao , Kawamoto Shin-ichiro , Yamada Masahide , Ishida Naoko , Kadoya Toshihiko , Tomiyama Yoshiaki , Kincade Paul W. , Matsuzawa Yuji 
Published: December 2002

AbstractSeveral reports have described “multifunctional” eukaryotic mRNAs producing more than one protein through alternative translational initiation at multiple AUG codons. There are 2 such codons in the 5′ region of our recently cloned limitin gene where 2 open reading frames overlap by 34 nucleotides. The deduced protein translated from the first ATG contains 33 amino acids, lacks a signal peptide, and has no obvious effects on the transfected 293T cells. We found that the second ATG is more effective as a translational initiation site than the first ATG and yields a secreted protein of 182 amino acids with the same activity as products made with full-length limitin cDNA. Immunohistochemical and reverse transcription–polymerase chain reaction analysis revealed that the longer limitin protein is produced by mature T lymphocytes in spleen and thymus as well as by bronchial epithelial and salivary duct cells in healthy mice. Properties of recombinant limitin were determined, revealing it to be a serologically distinct, heat- and acid-stable, heparin-binding glycoprotein with the potential for dimerization. Although the longer limitin protein is structurally and characteristically related to type I interferons, its production is uniquely regulated by translation as well as transcription.
Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells
Authors: Sarfati Marika , Mateo Véronique , Baudet Sylvie , Rubio Manuel , Fernandez Christine , Davi Fréderic , Binet Jacques-Louis , Delic Jozo , Merle-Béral Hélène 
Published: December 2002

AbstractType 4 phosphodiesterase (PDE4) inhibitors reportedly induce apoptosis in chronic lymphocytic leukemia (CLL) cells. Following clinical improvement of one previously untreated CLL patient with sildenafil therapy, we evaluated the in vitro induction of apoptosis in CLL cells by 4 PDE5/6 inhibitors, including sildenafil, vardenafil, zaprinast, and methoxyquinazoline (MQZ). After 24 hours of culture, the various PDE inhibitors differed in their ability to induce apoptosis, with zaprinast displaying no killing effect. Normal B cells isolated from control donors were totally resistant to PDE-induced apoptosis. Vardenafil was 3 and 30 times more potent an inducer of apoptosis than sildenafil and MQZ, respectively. Both vardenafil and sildenafil failed to elevate adenosine 3′5′ cyclic monophosphate (cAMP) levels, largely excluding an inhibitory effect on cAMP-PDE3, -PDE4, and -PDE7. Vardenafil- or sildenafil-treated B-CLL cells displayed up to 30% intracellular active caspase 3. Drug-induced apoptosis was inhibited by the caspase inhibitor z-VAD.fmk, prevented by interleukin-4 (IL-4), and significantly reduced by stromal-derived factor1-α (SDF-1α). We conclude that vardenafil and sildenafil induce caspase-dependent apoptosis of B-CLL cells in vitro and thus might be considered in the treatment of CLL patients. However, further in vivo investigations should be warranted.
Mutations in the murine erythroid α-spectrin gene alter spectrin mRNA and protein levels and spectrin incorporation into the red blood cell membrane skeleton
Authors: Wandersee Nancy J. , Birkenmeier Connie S. , Bodine David M. , Mohandas Narla , Barker Jane E. 
Published: December 2002

AbstractTetramers of α- and β-spectrin heterodimers, linked by intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either α- or β-spectrin can result in severe hereditary spherocytosis (HS) or hereditary elliptocytosis (HE) in mice and humans. Four mouse mutations,sph, sphDem,sph2BC, and sphJ, affect the erythroid α-spectrin gene, Spna1, on chromosome 1 and cause severe HS and HE. Here we describe the molecular alterations in α-spectrin and their consequences insph2BC/sph2BC andsphJ/sphJerythrocytes. A splicing mutation, sph2BC initiates the skipping of exon 41 and premature protein termination before the site required for dimerization of α-spectrin with β-spectrin. A nonsense mutation in exon 52, sphJ eliminates the COOH-terminal 13 amino acids. Both defects result in instability of the red cell membrane and loss of membrane surface area. Insph2BC/sph2BC, barely perceptible levels of messenger RNA and consequent decreased synthesis of α-spectrin protein are primarily responsible for the resultant hemolysis. By contrast, sphJ/sphJmice synthesize the truncated α-spectrin in which the 13-terminal amino acids are deleted at higher levels than normal, but they cannot retain this mutant protein in the cytoskeleton. ThesphJdeletion is near the 4.1/actin-binding region at the junctional complex providing new evidence that this 13-amino acid segment at the COOH-terminus of α-spectrin is crucial to the stability of the junctional complex.
Rapamycin-induced G1 arrest in cycling B-CLL cells is associated with reduced expression of cyclin D3, cyclin E, cyclin A, and survivin
Authors: Decker Thomas , Hipp Susanne , Ringshausen Ingo , Bogner Christian , Oelsner Madlene , Schneller Folker , Peschel Christian 
Published: December 2002

AbstractIn B-cell chronic lymphocytic leukemia (B-CLL), malignant cells seem to be arrested in the G0/early G1phase of the cell cycle, and defective apoptosis might be involved in disease progression. However, increasing evidence exists that B-CLL is more than a disease consisting of slowly accumulating resting B cells: a proliferating pool of cells has been described in lymph nodes and bone marrow and might feed the accumulating pool in the blood. Rapamycin has been reported to inhibit cell cycle progression in a variety of cell types, including human B cells, and has shown activity against a broad range of human tumor cell lines. Therefore, we investigated the ability of rapamycin to block cell cycle progression in proliferating B-CLL cells. We have recently demonstrated that stimulation with CpG-oligonucleotides and interleukin-2 provides a valuable model for studying cell cycle regulation in malignant B cells. In our present study, we demonstrated that rapamycin induced cell cycle arrest in proliferating B-CLL cells and inhibited phosphorylation of p70s6 kinase (p70s6k). In contrast to previous reports on nonmalignant B cells, the expression of the cell cycle inhibitor p27 was not changed in rapamycin-treated leukemic cells. Treatment with rapamycin prevented retinoblastoma protein (RB) phosphorylation in B-CLL cells without affecting the expression of cyclin D2, but cyclin D3 was no longer detectable in rapamycin-treated B-CLL cells. In addition, rapamycin treatment inhibited cyclin-dependent kinase 2 activity by preventing up-regulation of cyclin E and cyclin A. Interestingly, survivin, which is expressed in the proliferation centers of B-CLL patients in vivo, is not up-regulated in rapamycin-treated cells. Therefore, rapamycin interferes with the expression of many critical molecules for cell cycle regulation in cycling B-CLL cells. We conclude from our study that rapamycin might be an attractive substance for therapy for B-CLL patients by inducing a G1 arrest in proliferating tumor cells.
Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571)
Authors: Scheuring Urban J. , Pfeifer Heike , Wassmann Barbara , Brück Patrick , Atta Johannes , Petershofen Eduard K. , Gehrke Brigitte , Gschaidmeier Harald , Hoelzer Dieter , Ottmann Oliver G. 
Published: December 2002

AbstractThe Abl kinase inhibitor imatinib mesylate (STI571) has significant and rapid antileukemic activity in Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia (Ph+ ALL) but such activity is usually of short duration except for a small proportion of patients. To determine the prognostic significance of early Bcr-Abl levels and changes in peripheral blood (PB) and bone marrow (BM), serial samples of 56 patients with relapsed or refractory Ph+ ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction (PCR). Imatinib induced a complete hematologic response (CHR) or complete marrow response (marrow-CR) in 40 patients (good responders) and a partial (n = 2) or no (n = 14) remission in the remaining patients (poor responders). Compared with baseline, the median Bcr-Abl/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios decreased significantly in PB by 2.65, 2.64, and 3.11 log steps after 2 weeks, 4 weeks, and at the time of best response, respectively. In BM, the decline of median Bcr-Abl/GAPDH was 0.75, 1.37, and 2.78 logs, respectively. Thus, Bcr-Abl levels decreased more rapidly in PB than in BM (median time to best level 31 vs 39 days). Low Bcr-Abl/GAPDH ratios below 10−4 in PB and below 10−2 in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, Bcr-Abl levels (&lt; 10−2) in BM of good responders after 4 weeks discriminated between 2 groups of patients with significantly different median time to progression (139 vs 22 days). The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies.
Comprehensive banking of sibling donor cord blood for children with malignant and nonmalignant disease
Authors: Reed William , Smith Renée , Dekovic Florinna , Lee Joanna Y. , Saba Julie D. , Trachtenberg Elizabeth , Epstein Joanna , Haaz Steffany , Walters Mark C. , Lubin Bertram H. 
Published: December 2002

Abstract
Banking of cord blood (CB) for unrelated hematopoietic stem cell (HSC) transplantation is well established. However, directed-donor banking of CB for siblings in a current good tissue practices (cGTP) environment has not previously been investigated. Families were eligible for the present study if they were caring for a child with a disorder treatable by HSC transplantation and expecting the birth of a full sibling. We devised standard operating procedures and policies to address eligibility, donor recruitment, donor and recipient evaluation, CB collection, shipping, graft characterization, storage, and release of CB from quarantine. Many of these policies are distinctly different from those established for unrelated-donor CB banks. We enrolled 540 families from 42 states. Collections occurred at several hundred different hospitals. No family was deferred on the basis of health history or infectious disease testing, but departures from standard donor suitability criteria were documented. Disease categories for sibling recipients included malignancy, sickle cell anemia, thalassemia major, nonmalignant hematological conditions, and metabolic errors. Mean CB volume (including anticoagulant) was 103.1 mL; mean nucleated cell count was 8.9 × 108. Cell dose exceeded 1.5 × 107 nucleated cells per kilogram for 90% of banked units. Seventeen units (3.4%) have been transplanted. Sixteen of the 17 CB allograft recipients had stable engraftment of donor cells. Remote-site collection of sibling donor CB can be accomplished with a high success rate and in a cGTP-guided environment. The cellular products have been used successfully for transplantation; their number and characteristics should be adequate to support the first prospective clinical investigations of sibling CB transplantation.