Pain in Severe Dementia: Self‐Assessment or Observational Scales?

OBJECTIVES: To assess the performance of self-assessment scales in severely demented hospitalized patients and to compare it with observational data. DESIGN: Prospective clinical study. SETTING: Geriatrics hospital and a geriatric psychiatry service. PARTICIPANTS: All patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for dementia, with a Mini-Mental State Examination score less than 11 and a Clinical Dementia Rating score of 3. MEASUREMENTS: Three self-assessment tools--the verbal, horizontal visual, and faces pain scales--were administered in randomized order. A nursing team independently completed an observational pain rating scale. Main outcomes were comprehension (ability to explain scale use and correctly indicate positions for no pain and extreme pain, on two separate occasions), inter- and intrarater reliability, and comparison of pain intensities measured by the different scales. RESULTS: Sixty-one percent of 129 severely demented patients (mean age 83.7, 69% women) demonstrated comprehension of at least one scale. Comprehension rates were significantly better for the verbal and the faces pain scales. For patients who demonstrated good comprehension, the inter- and intrarater reliability of the three self-assessment scales was high (intraclass correlation coefficient=0.88-0.98). Correlation between the three self-assessment scales was moderate to strong (Spearman correlation coefficient (r)=0.45-0.94; P<.001). Observational rating correlated at least moderately with self-assessment (r=0.25-0.63), although for patients reporting pain, the observational rating scale underestimated severity compared with all three self-assessment scales. CONCLUSION: Clinicians should not apply observational scales routinely in severely demented patients, because many are capable of reliably reporting their own pain.     

The impact of HLA-DRB1*0405 on disease severity in Korean patients with seropositive rheumatoid arthritis

Many reports have described HLA-DRB1 genes as having an influence on disease severity and susceptibility in rheumatoid arthritis (RA). Studies were undertaken to define the effect of RA-associated alleles on disease severity in Korean patients with seropositive RA. The results indicate that the most common RA susceptibility allele, HLA- DRB1*0405, is significantly associated with bony erosion, joint deformity and extra-articular manifestations. However, RA-associated alleles in Koreans have less effect on nodular disease than in Caucasians. This suggests that the presence of RA-associated alleles, especially HLA-DRB1*0405, seems to be a prognostic marker for severe erosive disease in Koreans.      

Severe congenital neutropenia: abnormal growth and differentiation of myeloid progenitors to granulocyte colony-stimulating factor (G-CSF) but normal response to G-CSF plus stem cell factor

Several mechanisms have been proposed to explain the pathogenesis of severe congenital neutropenia (SCN); however, the mechanism(s) still remains unknown. In particular, clinical observations suggest that abnormal responsiveness of myeloid progenitors to hematopoietic growth factors (HGFs) is a possible mechanism. Therefore, to better define the status of hematopoietic progenitors in the bone marrow (BM) of patients with SCN, the responsiveness of myeloid progenitors to HGFs from two SCN patients was compared with the responsiveness of progenitors from healthy individuals. BM cells (BMCs) from the first SCN patient required higher (10- to 100-fold) concentrations of granulocyte colony- stimulating factor (G-CSF) to achieve maximal and half-maximal colony growth in vitro compared with BMCs from controls. In contrast, the dose- response of interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM- CSF) in colony formation was normal. Interestingly, IL-3, GM-CSF, and G- CSF at optimal doses showed reduced ability to induce neutrophil differentiation of BMCs from a SCN patient compared with BMCs from controls. Despite an abnormal responsiveness of mature myeloid progenitors to G-CSF in this SCN patient, myeloid progenitors responsive to the combination of stem cell factor (SCF) and G-CSF showed normal dose-response. In contrast to G-CSF alone, the combination of G-CSF and SCF induced the formation of neutrophils almost to the same extent compared with cultures of normal BMCs. Furthermore, also on BM progenitor cells obtained from the second patient with SCN, SCF highly synergized with G-CSF to promote neutrophil progenitor cell growth and differentiation in vitro. Thus, these results indicate that one mechanism of the pathogenesis in SCN patients is reduced responsiveness of neutrophil progenitor cells to G- CSF and that SCF can enhance the responsiveness of these cells to G-CSF.     

Long-term follow-up of blood donors with indeterminate human immunodeficiency virus type 1 results on Western blot

BACKGROUND: At present, tens of thousands of United States blood donors who are at low risk for human immunodeficiency virus type 1 (HIV-1) infection are indefinitely deferred. These persons are repeatably reactive for HIV-1 antibody in enzyme immunoassay (EIA) and are indeterminate in Western blot. STUDY DESIGN AND METHODS: To determine the significance and persistence of anti-HIV-1 reactivity in plasma from volunteer blood donors with HIV-1-indeterminate Western blots, 66 donors were retested for HIV-1 antibody by the same manufacturers' EIA and Western blot 5 to 7 years after the initial Western blot. In addition, donors' peripheral blood mononuclear cells were tested by polymerase chain reaction (PCR) for HIV-1 DNA gag sequences. RESULTS: Thirty-five (53%) of 66 donors were still repeatedly reactive for HIV-1 on EIA and indeterminate on Western blot, 23 (35%) were negative on EIA and indeterminate on Western blot, 7 (11%) were negative in EIA and Western blot, and 1 (2%) was repeatedly reactive on EIA and negative on Western blot. Donors with persistently indeterminate Western blots had a band pattern nearly identical to that on the original Western blot. No donor was positive in Western blot, p24 antigen, or PCR testing. No donor had signs or symptoms of HIV-1 infection. CONCLUSION: Long-term follow-up of Western blot-indeterminate blood donors does not reveal evidence of HIV-infection. A mechanism to return these donors to the donor pool should be considered.     

Direct growth suppression of myeloid bone marrow progenitor cells but not cord blood progenitors by human cytomegalovirus in vitro

Recently, considerable interest has arisen as to use cord blood (CB) as a source of hematopoietic stem cells for allogenic transplantation when bone marrow (BM) from a familial HLA-matched donor is not available. Because human cytomegalovirus (HCMV) has been shown to inhibit the proliferation of BM progenitors in vitro, it was important to examine whether similar effect could be observed in HCMV-infected CB cells. Therefore, the effect of HCMV challenge on the proliferation of myeloid progenitors from BM and CB was compared using both mononuclear cells (MNC) and purified CD34+ cells. A clinical isolate of HCMV inhibited the colony formation of myeloid BM progenitors responsive to granulocyte-macrophage colony-stimulating factor (CSF), granulocyte- CSF, macrophage-CSF, interleukin-3 (IL-3) and the combination of IL-3 and stem cell factor (SCF). In contrast, colony growth of CB progenitors was not affected. In addition, HCMV inhibited directly the growth of purified BM CD34+ cells responsive to IL-3 and SCF in single cell assay by 40%, wheras the growth of CD34+ progenitors obtained from CB was not suppressed. The HCMV lower matrix structural protein pp65 and HCMV DNA were detected in both CB and BM CD34+ cells after in vitro challenge. However, neither immediate early (IE)-mRNA nor IE proteins were observed in infected cells. Cell cyclus examination of BM and CB CD34+ cells revealed that 25.7% of BM progenitors were in S + G2/ M phase wheras only 10.7% of the CB progenitors. Thus, a clinical isolate of HCMV directly inhibited the proliferation of myeloid BM progenitors in vitro wheras CB progenitors were not affected. This difference in the susceptibility of CB and BM cells to HCMV may partly be caused by the slow cycling rate of naive CB progenitors compared to BM progenitors at the time of infection.     

Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18

Platelets bound to thrombogenic surfaces have been shown to support activation-dependent firm adhesion of neutrophils in flow following selectin-mediated tethering and rolling. The specific receptor(s) responsible for mediating adhesion-strengthening interactions between neutrophils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutrophils has not been tested. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte binding in vascular shear flow and emigration at thrombogenic sites. Our results demonstrate that the beta 2-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta 2-integrin receptors, formed P-selectin-mediated rolling interactions, but were unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengthening interaction observed for healthy neutrophils could be specifically inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercellular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta 2-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil transmigration across platelets bound to fibronectin-coated polycarbonate filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an important role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury.     

Cognitive features in euthymic bipolar patients in old age

Objectives:  Studies of cognition in bipolar disorder (BD) have reported impairments in processing speed, working memory, episodic memory, and executive function, but they have primarily focused on young and middle-aged adults. In such studies, the severity of cognitive deficits increases with the duration of illness. Therefore, one would expect more pronounced deficits in patients with longstanding BD. The first aim of the present study was to determine the pattern and the magnitude of cognitive impairment in older euthymic BD patients. The second aim was to explore the interrelationship between these cognitive deficits and determine whether they reflect a single core impairment or the co-occurrence of independent cognitive deficits.
Methods:  Twenty-two euthymic elderly BD patients and 22 controls, matched for gender, age, and education, underwent a comprehensive neuropsychological assessment.
Results:  Compared to controls, BD patients had significantly reduced performance in processing speed, working memory, verbal fluency, and episodic memory, but not in executive function. Hierarchical regression analyses showed that verbal fluency and working memory impairments were fully mediated by changes in processing speed. This was not the case for the episodic memory dysfunction.
Conclusion:  The cognitive profile in older euthymic BD cases is similar to the one described in younger BD cohorts. Our results further suggest that impaired processing speed plays a major role in the cognitive changes observed in BD patients except for deficits in episodic memory, thus providing strong evidence that processing speed and episodic memory are two core deficits in elderly BD patients.     

Screening for children’s depression symptoms in Greece: the use of the Children’s Depression Inventory in a nation-wide school-based sample

The objective of this study is to determine the level of depressive symptoms among a sample of Greek children aged 8–12 years, as measured by the Greek Children’s Depression Inventory (CDI), as well as to examine CDI’s psychometric properties. A nationwide school-based sample of 650 children was initially recruited and depressive symptoms were assessed with the CDI among 538 children who provided all relevant information. Statistical evaluation included assessment of CDI internal reliability, test–retest reliability, determination of age, gender and socioeconomic status (SES) effects. Based on the distributions of CDI scores observed in this normative sample, a recommended cutoff score, identifying a high probability of serious levels of depressive symptoms that need to be further evaluated, was defined. Internal reliability and test–retest reliability were satisfactory and the expected associations with age and gender were observed. High SES was correlated with significantly less depression symptoms. The prevalence of depressive risk, when the cutoff point of 19 or 13 was taken as threshold, was much lower than those obtained from studies in other countries. The cutoff point of 15, corresponding to 90th percentile of the present sample, may be used as a screening threshold for further assessment. The present results are encouraging providing evidence about the psychometric properties of the CDI and implications for child mental health promotion planning in Greece. Further validation of the CDI against other measures and psychiatric diagnoses is needed.