Health-related quality of life and pressure ulceration assessment in patients treated in the community

Little is known of the impact of pressure ulceration on adult patients' health-related quality of life. The purpose of this study was to determine the impact pressure ulceration has on pressure ulcer patients cared for in the community. A case control study design was used by drawing a random sample from patients receiving community nursing care, stratified by the presence of pressure ulceration. In all, 75 patients with pressure ulcers were compared with 100 controls without ulcers using the four-point ulcer grading scale described by United Kingdom consensus guidelines. Patients were interviewed using the Short Form-36 (SF-36) questionnaire and activities of daily living assessed using the modified Barthel scale. Patients with pressure ulcers had significantly poorer physical function (mean difference (d) = 37.6, 95% CI 28.6-46.6, p < 0.001) and social functioning (d = 33.9, 95 % CI 24.0-43.9, p < 0.001) than published age- and sex-matched normative data from the United Kingdom. The difference between cases and controls was much smaller in these domains, with neither approaching statistical significance. After adjustment for age and gender, scores for bodily pain were poorer in patients with no ulceration (d = -10.5, 95% CI - 20.6 to - 0.4, p = 0.042) indicating greater pain in these patients compared with the cases with ulceration. Activities of daily living determined by the modified Barthel scale showed reduced self-care (d = -7.6, 95% CI -12.5 to - 2.7, p = 0.010) and mobility (d = -9.2, 95% CI -14.6 to - 3.8, p = 0.001) in patients with pressure ulceration. The overall ability to perform these activities was also significantly poorer in this group (d = -16.3, 95% CI -27.3 to -5.3, p = 0.004). While patients with pressure ulceration experience some deficits in their health-related quality of life compared with a normal population, these differences are similar to those experienced by other patients receiving community nursing care.     

Three novel PROC gene lesions causing protein C deficiency

Hallam PJ, Mannucci P, Tripodi A, Bevan D, Laursen B, Tengborn L, Wacey A, Cooper DN. Three novel PROC gene lesions causing protein C deficiency. Clin Genet 1998: 54: 231–233. 0 Munksgaard, 1998
Missense mutations. three of them novel (Am210→Val, Asn248→ Ile, Ah355→Val), were found in the protein c ( PROC ) genes of 7 patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX causing hdernophilia B and the use of molecular modelling has provided explanations as to how these lesions might alter either the structure, function or secretion of the protein C molecules encoded.     

Differential susceptibility of human T(h)1 versus T(h) 2 cells to induction of anergy and apoptosis by ECDI/antigen-coupled antigen-presenting cells

Antigen-coupled antigen-presenting cells (APC) serve as potent tolerogens for inhibiting immune responses in vivo and in vitro, apparently by providing an antigen-specific signal through the TCR in the absence of co-stimulation. Although this approach has been well studied in rodents, little is known about its effects on human T cells. We evaluated the specificity and mechanisms of tolerization of human T cells in vitro using monocyte-enriched adherent cells that were pulsed with antigen and treated with the cross-linker, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (ECDI). Autologous antigen-coupled APC selectively tolerized T cells of the T(h)1 but not T(h)2 lineage through a mechanism that involved both antigen-specific and antigen-non-specific elements. The tolerization process was dependent on the ECDI and antigen concentration, and the coupling time, and was reflected by initial up-regulation of CD25. However, upon re-stimulation with fresh APC and antigen, tolerized T(h)1 cells failed to proliferate or to produce T(h)1 cytokine message or secreted protein, had decreased expression of CD25, CD28 and B7 and increased expression of MHC class II molecules, and demonstrated an enhanced commitment to apoptosis. T(h)1 cell tolerization could be prevented by adding anti-CD28 antibody, IL-2 or untreated APC at the same time as the ECDI/antigen-coupled APC, or reversed by adding anti-CD28 antibody or IL-2 upon re-stimulation with fresh APC plus antigen. Thus, the tolerizing effect of ECDI/antigen-coupled APC on human T(h)1 cells appears to involve a reversible anergy mechanism leading to apoptosis, whereby the targeted T cells receive full or partial activation through the TCR, without coordinate co-stimulation. These data suggest dichotomous signaling requirements for inactivating cells of the T(h)1 and T(h)2 lineages that may have important implications for treatment of T(h)1-mediated autoimmune or inflammatory diseases.     

Severity of demyelination in vivo correlates with serum myelination inhibition activity in guinea pigs having a new form of experimental allergic encephalomyelitis

Guinea pigs received a suboptimal transfer of lymphocytes sensitized to myelin basic protein (BP) and were then immunized with guinea pig BP, BP plus chicken brain or chicken myelin, or chicken brain alone. Sera from these animals were tested for the presence of myelinotoxic antibodies, as detected by the myelination inhibition assay. Myelination inhibition activity correlated with the histologic severity of demyelination.     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.