Problems in using health survey questionnaires in older patients with physical disabilities. The reliability and validity of the SF-36 and the effect of cognitive impairment.

Reliability and validity of the SF-36 Health Survey Questionnaire was assessed in older rehabilitation patients, comparing cognitively impaired with cognitively normal subjects. The SF-36 was administered by face-to-face interview to 314 patients (58-93 years) in the day hospital and rehabilitation wards of a department of medicine for the elderly. Reliability was measured using Cronbach's alpha (for internal consistency) on the main sample and intraclass correlation coefficients on a test-retest sample; correlations with functional independence measure (FIM) were examined to assess validity. In 203 cognitively normal patients (Mini-Mental State Examination > or =24), Cronbach's alpha scores on the eight dimensions of the SF-36 ranged from 0.545 (social function) to 0.933 (bodily pain). The range for the 111 cognitively impaired patients was 0.413-0.861. Cronbach's alpha values were significantly higher (i.e. reliability was better) in the cognitively normal group for bodily pain (P = 0.003), mental health (P = 0.03) and role emotional (P = 0.04). In test-retest studies on a further 67 patients, an intraclass correlation coefficient of 0.7 was attained for five out of eight dimensions in cognitively normal patients, and four out of eight dimensions in the cognitively impaired. Only the physical function dimension in the cognitively normal group attained the criterion level (r > 0.4) for construct validity when correlated with the FIM. In this group of older physically disabled patients, levels of reliability and validity previously reported for the SF-36 in younger subjects were not attained, even on face-to-face testing. Patients with coexistent cognitive impairment performed worse than those who were cognitively normal.

Problems in using health survey questionnaires in older patients with physical disabilities. Can proxies be used to complete the SF-36?

BACKGROUND: The SF-36 Health Survey questionnaire has been proposed as a generic measure of health outcome. However, poor rates of return and high levels of missing data have been found in elderly subjects and, even with face-to-face interview, reliability and validity may still be disappointing, particularly in cognitively impaired patients. These patients may be the very patients whose quality of life is most affected by their illness and their exclusion will lead to biased evaluation of health status. A possible alternative to total exclusion is the use of a proxy to answer on the patient's behalf, but few studies of older people have systematically studied patient-proxy agreement. OBJECTIVE: To compare the agreement between patients, lay and professional proxies when assessing the health status of patients with the SF-36. METHODS: The SF-36 was administered by interview to 164 cognitively normal, elderly patients (Mini-mental State Examination 24 or more) referred for physical rehabilitation. The SF-36 was also completed by a patient-designated lay proxy (by post) and a professional proxy. Agreement between proxies and patients was measured by intraclass correlation coefficients (ICCs), and a bias index. RESULTS: Professional proxies were better able to predict the patients' responses than were the lay proxies. Criterion levels of agreement (ICC 0.4 or over) were attained for four of the eight dimensions of the SF-36 by professional proxies, but for only one dimension by lay proxies. In professional proxies, the magnitude of the bias was absent or slight (<0.2) for six of the eight dimensions of the SF-36 with a small (0.2-0.49) negative bias for the other two. Lay proxies showed a negative bias (i.e. they reported poorer function than did the patients themselves) for seven of the eight dimensions of the SF-36 (small in two and moderate (0.5-0.79) in five). CONCLUSIONS: For group comparisons using the SF-36, professional proxies might be considered when patients cannot answer reliably for themselves. However, in the present study, lay proxy performance on a postal questionnaire showed a strong tendency to negative bias. Further research is required to define the limitations and potentials of proxy completion of health status questionnaires.

Characterization of the binding properties and physiological action of divalinal-angiotensin IV, a putative AT4 receptor antagonist.

Divalinal-Ang IV [V psi (CH2-NH2)YV psi (CH2-NH2)HPF] is being employed increasingly as a specific AT4 antagonist. This use, which necessitates a comprehensive physiological and pharmacological evaluation of Divalinal-Ang IV's functional and receptor binding characteristics in order to ensure its efficacy and specificity, was the stimulus for this study using bovine adrenal membranes. [125I]Ang IV and [125I]Divalinal-Ang IV were shown to bind with high affinity to a similar number of binding sites, suggesting that both bound the same receptor. This notion was verified by competition curves using [125I]Ang IV and [125I]Divalinal-Ang IV that indicated identical rank order affinities for several angiotensin-related peptides and 100% cross-displacement by Ang IV and Divalinal-Ang IV. Furthermore, an autoradiographic comparison of [125I]Ang IV and [125I]Divalinal-Ang IV in 20 microns sections of bovine adrenals revealed near identical binding distributions characterized by heavy binding in the glomerulosa layer and the medulla. Physiological studies in which test compounds were injected into the internal carotid of the rat and cerebral blood flor (CBF) was measured by laser Doppler flowmetry indicated that pretreatment with Divalinal-Ang IV, but not DuP 753 or PD123177, blocked the increased flow observed with Ang IV infusion. Conversely, DuP 753, but not Divalinal-Ang IV or PD123177, inhibited the decrease in flow witnessed with Ang II. Metabolic stability studies utilizing rat kidney homogenates as a peptidase source, demonstrated that the structural changes present in Divalinal-Ang IV greatly increased its resistance to metabolism as compared to Ang IV. Together, these studies show that Divalinal-Ang IV is a stable, efficacious and specific inhibitor of AT4 receptors.

Identification and characterization of a novel angiotensin binding site in cultured vascular smooth muscle cells that is specific for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV.

This study demonstrates the existence of a previously unrecognized class of angiotensin binding sites on vascular smooth muscle that exhibit high affinity and specificity for the hexapeptide (3-8) fragment of angiotensin II (AngIV). Binding of [125I]AngIV is saturable, reversible and describes a pharmacologic profile that is distinct and separate from the classic AT1 or AT2 angiotensin receptors. Saturation binding studies utilizing cultured vascular smooth muscle cells obtained from bovine aorta (BVSM) revealed that [125I]AngIV bound to a single high affinity site with an associated Hill coefficient of 0.99 +/- 0.003, exhibiting a KD = 1.85 +/- 0.45 nM and a corresponding Bmax = 960 +/- 100 fmol mg-1 protein. Competition binding curves in BVSM demonstrated the following rank order effectiveness: AngIV > AngII(3-7) >> AngIII > Sar1,Ile8 AngII > AngII > AngII(1-7) > AngII(4-8), DuP 753, PD123177. The presence of the non-hydrolyzable GTP analog GTP gamma S, had no effect on [125I]AngIV binding affinity in BVSM. The presence of this novel angiotensin binding site on smooth muscle in high concentration suggests the possibility that this system may play an important, yet unrecognized role in vascular control.

Zinc binding by retroviral integrase.

Zinc binding by integrase from Moloney murine leukaemia virus and a protein A fusion protein containing integrase from human immunodeficiency virus type 1 was demonstrated by a zinc blotting technique using 65ZnCl2. Autoradiography revealed a clear band that was absent from the appropriate controls. This band co-migrated with the major band in Coomassie-stained gels and in immunoblots. This binding activity was retained in the presence of competing divalent cations and was sensitive to oxidation. This is the first demonstration of zinc binding by intact retroviral integrase.

Mapping of a visceral leishmaniasis-specific immunodominant B-cell epitope of Leishmania donovani Hsp70.

We have shown that a member of the 70-kDa heat shock protein (Hsp70) family is a major target of the humoral immune response during Leishmania donovani infection. A recombinant fusion protein was recognized by sera from 92% (35 of 38) of patients with visceral leishmaniasis, including representatives from each of the major regions where it is endemic. Serological analysis of recombinant Hsp70, expressed by a series of deletion constructs, identified the carboxy-terminal region as the immunodominant site. This region, which is the most evolutionarily divergent part of the molecule, was recognized by all sera from patients with visceral leishmaniasis which exhibited an anti-Hsp70 response. Purified recombinant L. donovani Hsp70 was not recognized by sera from patients with cutaneous leishmaniasis, Chagas' disease, leprosy, malaria, or schistosomiasis. To determine the regions involved in antibody recognition, a series of overlapping peptides were synthesized on polyethylene pins by the Pepscan method, and a hexamer, EADDRA, was identified by the visceral leishmaniasis serum samples as an immunodominant B-cell epitope.