bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Constitutes Normal Hemoglobin Concentration in Community‐Dwelling Disabled Older Women?
Authors: Chaves Paulo H. M. , Xue Qian‐Li , Guralnik Jack M. , Ferrucci Luigi , Volpato Stefano , Fried Linda P. 
Published: October 2004

Objectives:To examine the associations between hemoglobin (Hb) concentration and (1) 5‐year all‐cause mortality and (2) serum erythropoietin (EPO), as the basis for the identification of data‐driven thresholds, and to assess the clinical relevance of mildly low Hb.Design:Prospective study.Setting:Population based.Participants:Community‐dwelling women aged 65 and older with moderate‐to‐severe disability—Women's Health and Aging Study I, Baltimore, Maryland, 1992–2000.Methods:Proportional hazards regression was used to model the relationship between baseline Hb (available for 686 subjects) and time to death. A generalized linear model was used to assess the cross‐sectional association between Hb and EPO in 641 subjects.Results:A curvilinear slope of steady mortality decrease up to the Hb threshold of 13.9 g/dL was observed. Hb of 11 g/dL was independently associated with greater mortality than the World Health Organization (WHO) low‐normal cutoff of Hb of 12 g/dL (hazard ratio (HR)=1.2, 95% confidence interval (CI)=1.1–1.4), whereas Hb of 14 g/dL was linked to 24% lower mortality (HR=0.76, 95% CI=0.63–0.92), after comprehensive adjustment for major health status and disease‐burden indicators. A curvilinear, statistically significant slope of steady EPO decrease with increasing Hb up to the threshold of 14.3 g/dL was consistently observed.Conclusion:The meaningfully lower mortality risk with higher Hb levels provides empirical evidence against the notion that Hb currently perceived as mildly low is clinically benign. Furthermore, the mortality risk gradient observed even within the WHO normal Hb range suggests that Hb levels higher than what is currently recommended might offer clinical advantage. The relationship between Hb and EPO provided supporting physiological evidence for this hypothesis.
Safety and Efficacy of Risedronate in Reducing Fracture Risk in Osteoporotic Women Aged 80 and Older: Implications for the Use of Antiresorptive Agents in the Old and Oldest Old
Authors: Boonen Steven , McClung Michael R. , Eastell Richard , El‐Hajj Fuleihan Ghada , Barton Ian P. , Delmas Pierre 
Published: October 2004

Objectives: To determine the efficacy of risedronate in reducing vertebral fracture risk in women aged 80 and older with osteoporosis.Design: Pooled analysis of data from three randomized, double‐blind, controlled, 3‐year‐fracture‐endpoint trials conducted from November 1993 to April 1998: Hip Intervention Program (HIP), Vertebral Efficacy with Risedronate Therapy—Multinational (VERT‐MN), and VERT‐North America (NA).Setting: Office‐based practices, research centers, and osteoporosis clinics in Europe, North America, and Australia.Participants: Osteoporotic (femoral neck bone mineral density T‐score < −2.5 standard deviations or at least one prevalent vertebral fracture) women aged 80 and older.Intervention: Patients received placebo (n=688) or risedronate 5 mg/d (n=704) for up to 3 years. All patients received 1,000 mg/d calcium and, if baseline levels were low, up to 500 IU/d vitamin D.Measurements: Cumulative incidence of new vertebral fractures.Results: After 1 year, the risk of new vertebral fractures in the risedronate group was 81% lower than with placebo (95% confidence interval=60–91%; P<.001). The number of women who needed to be treated to prevent one new vertebral fracture after 1 year was 12. This early onset of efficacy was consistent across the clinical programs, and antifracture efficacy was confirmed over 3 years. Risedronate was well tolerated, with a safety profile comparable with that of placebo.Conclusion: These findings provide the first evidence that, even in the very old, reducing bone resorption rate remains an effective treatment strategy for osteoporosis. Because each therapeutic agent used for the treatment of osteoporosis may have unique characteristics, the observations made in this study should not be assumed to apply to other bisphosphonates.
Cognitive Impairment in Chronic Kidney Disease
Authors: Kurella Manjula , Chertow Glenn M. , Luan Jennifer , Yaffe Kristine 
Published: October 2004

Objectives: To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD.Design: Cross‐sectional study.Setting: University‐affiliated ambulatory nephrology and dialysis practices.Participants: Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end‐stage renal disease (ESRD)) with a mean age±standard deviation of 62.5±14.3.Measurements: Three standardized cognitive tests, the Modified Mini‐Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six‐variable Modification of Diet in Renal Disease equation.Results: There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate (P=.01) and delayed (P<.001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function.Conclusion: Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD.
Pharmacotherapy of Pain in Depressed Older Adults
Authors: Unützer Jürgen , Ferrell Bruce , Lin Elizabeth H. B. , Marmon Tonya 
Published: October 2004

Objectives: To examine pharmacotherapy for pain in a sample of 1,801 depressed older primary care patients.Design: Cross‐sectional survey data collected from 1999 to 2001.Setting: Eighteen primary care clinics belonging to eight healthcare organizations in five states.Participants: One thousand eight hundred one patients aged 60 and older who met diagnostic criteria for major depression or dysthymia.Measurements: Diagnoses or treatment for chronic pain, functional impairment from pain, and use of over‐the‐counter and prescription analgesic medications.Results: One thousand four hundred sixteen (79%) participants reported functional impairment from pain in the previous month, and 1,024 (57%) reported a diagnosis of or treatment for chronic pain in the previous 3 years. Fifty‐one percent of those with recent functional impairment from pain reported any analgesic use, ranging from 31% to 75% across the participating healthcare organizations. Opioid analgesic use varied from 5% to 34%. Predictors of analgesic use included a history of chronic pain or arthritis and the degree of functional impairment from pain in the previous month. Differences in analgesic use across participating organizations remained significant after adjusting for clinical and demographic covariates.Conclusion: Most depressed older adults in the sample reported recent functional impairment from pain and a history of chronic pain, but almost half of those with functional impairment from pain did not report using analgesic medications. Participating organizations varied substantially in their use of analgesics, suggesting that there is room to improve the quality of pain management in depressed older adults.
How Should Clinicians Describe Hospice to Patients and Families?
Authors: Casarett David J. , Crowley Roxane L. , Hirschman Karen B. 
Published: October 2004

Objectives: To describe hospice enrollment from the perspective of bereaved family members and to identify information about hospice that would encourage patients and families to enroll sooner.Design: Cross‐sectional interviews.Setting: Three Medicare‐certified hospice organizations.Participants: One hundred family members of 100 patients who died in hospice.Measurements: Semistructured interviews assessed prior knowledge of hospice, patients' and physicians' involvement in the enrollment process, features of hospice that motivated enrollment, and features that patients and families wished they had learned about sooner.Results: Almost all family members (n=92) and patients (n=71) knew about hospice before the patient's illness. Almost half the patients (n=44) were not involved at all in the hospice enrollment decision. The patient's physician (n=51) or the patient or family (n=34) initiated most hospice discussions, but patients and families usually obtained information about hospice from a hospice representative (n=75) rather than from the patient's physician (n=22). Family members identified several kinds of information about hospice that were particularly helpful in deciding whether to enroll and described several aspects of hospice that they wished they had known about sooner.Conclusion: Many patients and families learn about hospice from someone other than the patient's physician, and most learn about valuable hospice features and services only after enrollment. By providing more information about hospice earlier in the illness course, clinicians may be able to facilitate more‐informed and more‐timely decisions about hospice enrollment.
Operationalizing a Frailty Index from a Standardized Comprehensive Geriatric Assessment
Authors: Jones David M. , Song Xiaowei , Rockwood Kenneth 
Published: October 2004

Objectives: To construct and validate a frailty index (FI) that is clinically sensible and practical for geriatricians by basing it on a routinely used comprehensive geriatric assessment (CGA) instrument.Design:  Secondary analysis of a 3‐month randomized, controlled trial of a specialized mobile geriatric assessment team.Setting: Rural Nova Scotia. Participants were seen in their homes.Participants: Frail older adults, of whom 92 were in the intervention group and 77 in the control group.Measurements: A standard CGA form that accounts for impairment, disability, and comorbidity burden was scored and summed as a frailty index (FI‐CGA). The FI‐GCA was stratified to describe three levels of frailty. Patients were followed for up to 12 months to determine how well the index predicted adverse outcomes (institutionalization or mortality, whichever came first).Results: The three levels of frailty were mild (FI‐CGA 0–7), moderate (FI‐CGA 7–13), and severe (FI‐CGA>13). Demographic and social traits were similar across groups, but greater frailty was associated with worse function (r=0.55) and mental status (r=0.33). Those with moderate and severe frailty had a greater risk of adverse outcomes than those with mild frailty (unadjusted hazard ratio=1.9 and 5.5, respectively). There was no difference between frailty groups in mean 3‐month goal‐attainment scaling scores. Intrarater reliability was 0.95.Conclusion: The FI‐CGA is a valid, reliable, and sensible clinical measure of frailty that permits risk stratification of future adverse outcomes.
A McLeod phenotype detected by random screening for K:‐4 [Kp(b–)] blood donors in Brazil
Authors: Wendel Silvano , Fontão‐Wendel Rita , Levi José Eduardo , Aravechia Maria Giselda , Bordokan Roberta F.S. , Russo David , Haddad Monica Santoro 
Published: October 2004

BACKGROUND:  The red blood cells of the McLeod phenotype have weak expression of Kell System antigens due to no expression of XK protein.STUDY DESIGN AND METHODS:  One blood donor reacted as K:‐4 [Kp(b–)] during a screening assay. Subsequent serologic studies demonstrated weak expression of K:4 and all other high‐incidence Kell system antigens tested; however, no expression of Kx antigen was observed.RESULTS:  One apparently healthy blood donor demonstrated low expression of K:2, K:4, K:5, K:7, K:14, K:22, and no Kx antigen in his red blood cells. His brother and mother showed the same weak expression, and his father showed normal expression of antigens tested. Flow cytometry studies confirmed the mother's status as a McLeod carrier female. Genotyping determined the presence of KEL2 and KEL4 alleles in mother and siblings. Southern blot with an exon‐1 probe showed fragments shorter than predicted for the siblings and the mother, suggesting a deletion. Polymerase chain reaction with primers spanning exon 1 and flanking regions displayed a similar pattern. Deoxyribonucleic acid sequence allowed the precise characterization of a deletion of 392 bp, beginning at the 5′ of the coding region up to nucleotide 201 of exon 1, which putatively abrogates the production of XK protein.CONCLUSION:  Two brothers with McLeod phenotype in a Brazilian blood‐donor population were identified. The molecular basis for this phenotype is a 392‐bp deletion spanning from 5′ of the coding region to exon 1 of the XK gene, never described before.
Severe hemolysis resulting from D incompatibility in a case of ABO‐identical liver transplant
Authors: Fung Mark K. , Sheikh Hina , Eghtesad Bijan , Lopez‐Plaza Ileana 
Published: October 2004

BACKGROUND:  Hemolysis due to D incompatibility in the setting of liver transplantation is less frequent than that associated with ABO incompatibility, but can represent an equally adverse event. Approximately 10 percent of ABO‐compatible liver transplants involve a D– donor and a D+ recipient.CASE REPORT:  A case of severe D incompatibility resulting from liver transplantation in a 50‐year‐old O Rh+ man with end‐stage liver disease who received an O Rh– liver allograft is reported. A declining hemoglobin level complicated the patient's postoperative course with laboratory evidence of anti‐D–mediated hemolysis. Investigations revealed that the transplanted liver was from a female O Rh– donor with detectable antibodies against D, C, and K. The severity of the hemolytic anemia was such that the patient required two separate red blood cell (RBC) exchanges and intermittent RBC transfusions over the course of almost a year. In addition to the use of RBCs negative for D, C, and K, the patient underwent a variety of B‐cell suppressive therapies including glucocorticosteroids, mycophenolate mofetil, and rituximab. A normalization of hemoglobin levels and a decrease in serum bilirubin did not occur until after a splenectomy on postoperative Day 321.CONCLUSION:  This represents the sixth and most severe case reported of hemolysis resulting from D incompatibility in liver transplantation. When unexpected serologic findings are identified in a transplant recipient, obtaining more information on the donor may help guide transfusion support.
Molecular and serologic tracing of a transfusion‐transmitted hepatitis A virus
Authors: Gowland Peter , Fontana Stefano , Niederhauser Christoph , Taleghani Behrouz Mansouri 
Published: October 2004

BACKGROUND:  The transmission of hepatitis A virus (HAV) via blood transfusion has not been evidenced by molecular tracing so far.CASE REPORT:  A 33‐year‐old asymptomatic female volunteer made a whole‐blood donation. Thirteen days later an acute HAV infection was diagnosed. Retrospectively, a high viral load was measured by quantitative reverse transcription polymerase chain reaction (RT‐PCR) in the quarantine fresh‐frozen plasma (1.4 × 106 geq/mL), whereas immunoglobulin M (IgM) and G (IgG)/IgM anti‐HAV were not detectable and the alanine aminotransferase levels not elevated. The red blood cells have just been transfused on Day 14. The 63‐year‐old male recipient already was HAV seropositive. He did not develop clinical symptoms of HAV and anti‐HAV IgM was not detected. Seventy‐five days later, a 25‐fold increase in the anti‐HAV IgG/IgM titer was observed. Demonstrable HAV ribonucleic acid (RNA) in the recipient by means of RT‐PCR on Day 6, but not on Days 1 and 75, suggests that a transient reinfection did occur. Analyzed sequences of the HAV RNA in the donor and recipient were identical.CONCLUSION:  For the first time, transfusion‐transmitted HAV was evidenced by molecular and serologic tracing. The transmitted HAV can survive and replicate for a limited period despite the presence of anti‐HAV IgG.
The use of recombinant activated factor VII in three patients with central nervous system hemorrhages associated with factor VII deficiency
Authors: Huang Weei‐Yuarn , Kruskall Margot S. , Bauer Kenneth A. , Uhl Lynne , Shaz Beth H. 
Published: October 2004

BACKGROUND:  Recombinant activated factor VII (rFVIIa) is being tested to improve hemostasis in a variety of bleeding disorders. Clinical indications and efficacy are still being evaluated for this product.CASE REPORT:  Over a 17‐month period, rFVIIa was used to treat central nervous system hemorrhage in three patients who were found to have isolated FVII deficiency (21%, 40%, 27%). Patient A fell 30 feet, Patient B suffered a motor vehicle accident, and Patient C had a spinal cord hematoma. None of the patients had a history of bleeding diathesis. All three patients received rFVIIa after failing initial treatment with fresh‐frozen plasma.RESULTS:  Patient A was treated with 11 doses (initial dose 95 µg/kg; subsequent doses 8‐38 µg/kg) over 10 days; Patient B received 13 doses (45‐60 µg/kg) over 13 days; and Patient C received 5 doses (12‐24 µg/kg) over 4 days. The prothrombin time corrected from 16.2 ± 1.8 (mean ± SD) to 11.2 ± 1.6 seconds after infusion of rFVIIa, but returned to pretreatment level in 14 ± 4 hours. At the cessation of therapy, all patients showed neurologic improvement. No complications related to the infusion of rFVIIa occurred.CONCLUSION:   The use of rFVIIa may be of value both for its general effect on hemostasis, and specifically in the setting where there is a documented reduction in FVII. Doses lower than those used in patients with FVIII inhibitors appear to be effective in the setting of central nervous sytem hemorrhage.
Passive Immunization of Neonatal Mice againstPneumocystis cariniif. sp.murisEnhances Control of Infection without Stimulating Inflammation
Authors: Empey Kerry M. , Hollifield Melissa , Schuer Kevin , Gigliotti Francis , Garvy Beth A. 
Published: October 2004

ABSTRACTPneumocystis cariniiis an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to infection withPneumocystis. We have previously shown that there is a significant delay in clearance of the organisms from the lungs of neonatal mice compared to adults. Since alveolar macrophages are the effector cells responsible for killing and clearance ofPneumocystis, we have examined alveolar macrophage activity in neonatal mice. We found that alveolar macrophage activation is delayed about 1 week inPneumocystis-infected neonates compared to adults. Opsonization of the organism byPneumocystis-specific antibody resulted in increased clearance of the organism in neonatal mice; however, there was decreased expression of activation markers on neonatal alveolar macrophages and reduced levels of cytokines associated with macrophage activation. Mice born to immunized dams had significant amounts ofPneumocystis-specific immunoglobulin G in their lungs and serum at day 7 postinfection, whereas mice born to naïve dams had merely detectable levels. This difference correlated with enhancedPneumocystisclearance in mice born to immunized dams. The increase in specific antibody, however, did not result in significant inflammation in the lungs, as no differences in numbers of activated CD4+cells were observed. Furthermore, there was no difference in cytokine or chemokine concentrations in the lungs of pups born to immune compared to naïve dams. These findings indicate that specific antibody plays an important role inPneumocystisclearance from lungs of infected neonates; moreover, this process occurs without inducing inflammation in the lungs.
Expression of Type IV Pili by
Moraxella catarrhalis
Is Essential for Natural Competence and Is Affected by Iron Limitation
Authors: Luke Nicole R. , Howlett Amy J. , Shao Jianqiang , Campagnari Anthony A. 
Published: October 2004

ABSTRACT

Type IV pili, filamentous surface appendages primarily composed of a single protein subunit termed pilin, play a crucial role in the initiation of disease by a wide range of pathogenic bacteria. Although previous electron microscopic studies suggested that pili might be present on the surface of
Moraxella catarrhalis
isolates, detailed molecular and phenotypic analyses of these structures have not been reported to date. We identified and cloned the
M. catarrhalis
genes encoding PilA, the major pilin subunit, PilQ, the outer membrane secretin through which the pilus filament is extruded, and PilT, the NTPase that mediates pilin disassembly and retraction. To initiate investigation of the role of this surface organelle in pathogenesis, isogenic
pilA
,
pilT
, and
pilQ
mutants were constructed in
M. catarrhalis
strain 7169. Comparative analyses of the wild-type 7169 strain and three isogenic
pil
mutants demonstrated that
M. catarrhalis
expresses type IV pili that are essential for natural genetic transformation. Our studies suggest type IV pilus production by
M. catarrhalis
is constitutive and ubiquitous, although pilin expression was demonstrated to be iron responsive and Fur regulated. These data indicate that additional studies aimed at elucidating the prevalence and role of type IV pili in the pathogenesis and host response to
M. catarrhalis
infections are warranted.
Functional Analysis of
Bacillus anthracis
Protective Antigen by Using Neutralizing Monoclonal Antibodies
Authors: Brossier Fabien , Lévy Martine , Landier Annie , Lafaye Pierre , Mock Michèle 
Published: October 2004

ABSTRACT

Protective antigen (PA) is central to the action of the lethal and edema toxins produced by
Bacillus anthracis
. It is the common cell-binding component, mediating the translocation of the enzymatic moieties (lethal factor [LF] and edema factor) into the cytoplasm of the host cell. Monoclonal antibodies (MAbs) against PA, able to neutralize the activities of the toxins in vitro and in vivo, were screened. Two such MAbs, named 7.5 and 48.3, were purified and further characterized. MAb 7.5 binds to domain 4 of PA and prevents the binding of PA to its cell receptor. MAb 48.3 binds to domain 2 and blocks the cleavage of PA into PA63, a step necessary for the subsequent interaction with the enzymatic moieties. The epitope recognized by this antibody is in a region involved in the oligomerization of PA63; thus, MAb 48.3 does not recognize the oligomer form. MAbs 7.5 and 48.3 neutralize the activities of anthrax toxins produced by
B. anthracis
in mice. Also, there is an additive effect between the two MAbs against PA and a MAb against LF, in protecting mice against a lethal challenge by the Sterne strain. This work contributes to the functional analysis of PA and offers immunotherapeutic perspectives for the treatment of anthrax disease.