Field trial of graded care profile (GCP) scale: a new measure of care

AIM: The graded care profile (GCP) scale was developed as a practical tool in response to the Children Act 1989 to provide a measure of care in four areas: physical, safety, love, and esteem, on a bipolar continuum. This field trial was to assess its user friendliness and inter-rater agreement. METHODS: 43 nursery children and 11 registered for neglect were each scored on this scale independently by two different raters (health visitor and nursery teacher or social worker). Their inter-rater agreement was assessed by weighted kappa and user friendliness by time taken for and completeness of scoring. RESULTS: An almost perfect level of agreement was achieved in physical care (kappa = 0.899; confidence interval (CI) = 0.850 to 0.948), safety (kappa = 0.894; CI = 0.854 to 0.933), esteem (kappa = 0.877; CI = 0.808 to 0.946), and a substantial level in love (kappa = 0.785; CI = 0.720 to 0.849). Mean time taken for scoring was 20 minutes (range 10 to 30); of 54 paired scales, area of safety was not scored only in three by one of the raters. CONCLUSIONS: This scale appeared user friendly and provided grading of care with high inter-rater agreement. Its use in practice could provide an opportunity for useful comparison with other means of assessment of care, studying outcomes of different care profiles, targeting intervention, and monitoring change.     

Evaluation of serum CA 125 level as a tumor marker in borderline tumors of the ovary

Serum CA 125 was evaluated as a tumor marker in 85 patients with borderline ovarian tumors. Serum CA 125 levels were elevated preoperatively in 18 of 20 (90%) samples (median 66, range 5-272 U ml-1). Preoperative serum CA 125 levels did not correlate to FIGO stage. Preoperative serum CA 125 levels were elevated in seven of nine (78%) with serous tumors (median 131, range 5-272 U ml-1) and in all 11 with mucinous tumors (median 62, range 41-157 U ml-1). There was no significant difference in the CA 125 levels between these two histologic types. Postoperative serum CA 125 levels, measured 3-6 weeks after primary laparotomy, were significantly lower than the preoperative ones (P < 0.001). No difference in the postoperative CA 125 levels was found between those with and those without residual disease after surgery. Postoperative serum CA 125 levels were elevated in eight of 60 (13%) without residual tumor. None of these had relapsed at the time of analysis (26-87 months after surgery). Serum CA 125 levels tended to correlate with disease evolution during chemotherapy. Two with disease remissions had falling levels, one with stable disease had falling level and one with disease progression had rising level. Serum CA 125 samples were obtained before second-look laparotomy in seven patients. Two with negative findings at second-look had normal levels. Of five with positive findings at laparotomy only two had elevated serum CA 125 levels. Disease relapse was associated with elevated serum CA 125 levels in only one of six patients.     

Activation of the Epstein-Barr virus lytic cycle by the latex of the plant Euphorbia tirucalli

Exposure to the plant Euphorbia tirucalli has been proposed to be a cofactor in the genesis of endemic Burkitt's lymphoma (eBL). The purpose of this study was to examine the effects of unpurified E. tirucalli latex on Epstein-Barr virus (EBV) gene expression. A Burkitt lymphoma cell line was treated with varying dilutions of the latex and the effects on EBV gene expression were measured. We observed that the latex was capable of reactivating the EBV lytic cycle in a dose-dependent manner and at dilutions as low as 10(-6). Simultaneous treatment of cells with E. tirucalli latex and the protein kinase C inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride blocked lytic cycle activation. These data suggest that environmental exposure to the latex of E. tirucalli could directly activate the EBV lytic cycle and provide further evidence of a role for E. tirucalli in the aetiology of eBL.     

Prognosis of chronic low back pain: design of an inception cohort study

Background

Although clinical guidelines generally portray chronic low back pain as a condition with a poor prognosis this portrayal is based on studies of potentially unrepresentative survival cohorts. The aim of this study is to describe the prognosis of an inception cohort of people with chronic low back pain presenting for primary care.

Methods/Design

The study will be an inception cohort study with one year follow-up. Participants are drawn from a cohort of consecutive patients presenting with acute low back pain (less than 2 weeks duration) to primary care clinics in Sydney, Australia. Those patients who continue to experience pain at three months, and are therefore classified as having chronic back pain, are invited to participate in the current study. The cohort will be followed up by telephone at baseline, 9 months and 12 months after being diagnosed with chronic low back pain. Recovery from low back pain will be measured by sampling three different outcomes: pain intensity, interference with function due to pain, and work status. Life tables will be generated to determine the one year prognosis of chronic low back pain. Prognostic factors will be assessed using Cox regression.

Discussion

This study will determine the prognosis of chronic non-specific low back pain in a representative cohort of patients sourced from primary care. The results of this study will improve understanding of chronic low back pain, allowing clinicians to provide more accurate prognostic information to their patients.     

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from malaria and circulating antibodies to the carboxyl terminus of merozoite surface protein 1 (MSP1). Questions remain regarding the significance of cell-mediated immunity to MSP1 in conferring protection and inducing immunologic memory. Vaccine constructs have been based on the 42-kDa recombinant MSP1 protein (MSP1₄₂), which includes the 19-kDa (MSP1₁₉) and 33-kDa (MSP1₃₃) fragments containing the major B- and T-cell epitopes, respectively. To evaluate T-cell responses to the MSP1₃₃ fragment, two libraries of overlapping 18-mer peptides from the 3D7 and FVO MSP1₃₃ regions were used to screen a cohort of asymptomatic Kenyan adults. Gamma interferon (IFN-γ) measured by enzyme-linked immunospot assay (ELISPOT) at multiple time points assessed the magnitude and stability of these responses. The percentage of individuals with IFN-γ responses to single MSP1₃₃ peptides ranged from nil to 24%, were clustered among a subset of peptides, and were not consistently recalled over time. In comparison to peptide responses, IFN-γ ELISPOT responses to recombinant MSP1₄₂ were more prevalent, more frequently elicited by the 3D7 as opposed to the FVO allele, and more stable over time. The prevailing MSP1₃₃ genotype infection was 3D7, with few mixed infections and no sole FVO infections. This study demonstrates that immunity against MSP1₃₃ after cumulative natural infections consists of low-magnitude and difficult-to-detect IFN-γ responses. Although immunity against MSP1 alone will not confer protection against malaria, demonstrating a relative and sustained increase in T-cell immunity to MSP1 after vaccination would be a reasonable measurement of vaccine responsiveness.Infection with Plasmodium spp., the protozoan parasites responsible for malaria, results in an estimated 350 to 500 million infections per year with an ensuing 1 to 2 million deaths, the majority of which are caused by Plasmodium falciparum (45). Adults who have maintained lifelong residence in areas where malaria transmission is stable and of high intensity gradually develop naturally acquired immunity, an age-related phenomenon marked by a reduced frequency and severity of clinical malaria and high-density blood stage parasitemia relative to that of infants and children. Maintaining naturally acquired immunity is thought to require continuing exposure to malaria blood stage antigens mediated through asymptomatic low-density blood stage infection. A malaria vaccine that would accelerate the development of naturally acquired immunity during infancy and childhood has been a high priority for many years. The recent success of vector interventions, such as insecticide-treated bed nets, in decreasing transmission of P. falciparum in sub-Saharan Africa suggests that a blood stage vaccine would also be desirable in order to maintain the strength and duration of naturally acquired immunity among adults (17).Merozoite surface protein 1 (MSP1) is one of several candidates that have been considered for a blood stage vaccine. The primary ∼195-kDa MSP1 protein is expressed during schizogony and is processed initially to form a 42-kDa carboxyl-terminal fragment (MSP1₄₂) that remains attached to the merozoite surface. A second proteolytic cleavage results in the shedding of a 33-kDa fragment (MSP1₃₃) with formation of a 19-kDa carboxyl-terminal fragment (MSP1₁₉) anchored to the merozoite surface during invasion of the red blood cell (RBC) (4, 5). The 19-kDa fragment of MSP1 contains the major B-cell epitopes (18), the recognition of which is enhanced by T-helper epitopes in the 33-kDa fragment (1). Antibodies to MSP1₁₉ that interfere with RBC invasion by merozoites are one of several possible mechanisms by which naturally acquired immunity and experimental MSP1 vaccines may mediate protection against blood stage infection (27, 34). Studies of primates and mice immunized with MSP1 and more limited observations of residents of areas in which P. falciparum is endemic who have naturally acquired immunity and malaria-naïve human volunteers vaccinated with MSP1₄₂ suggest that T-cell responses to MSP1 are driven primarily by epitopes within the shed MSP1₃₃ fragment and that gamma interferon (IFN-γ) is important for optimal protective immunity (20, 23, 44, 46).A challenge to developing malaria vaccines that enhance protective immunity against blood stage parasitemia has been antigenic polymorphism that arises through selection by the human immune response; i.e., inclusion of several blood stage alleles might be required in order to mitigate selection of alleles not included in the vaccine. The P. falciparum msp1 gene has been divided into 17 blocks based on conserved, semiconserved, and variant DNA sequences (30). The C-terminal MSP1₄₂ protein is encoded by blocks 15 to 17; MSP1₃₃ is encoded by block 15 and 16. MSP1₄₂ alleles expressed by most clinical isolates and laboratory cultures of P. falciparum exist as either the MAD20 (3D7) or FVO (K1 or Wellcome) allele of MSP1₁₉ and MSP1₃₃ (although genetic recombination between the two [and other] alleles encoded by block 17 and block 15 to 16 also occurs). Whereas most studies from sub-Saharan Africa and other areas where malaria is endemic have characterized msp1 block 17 haplotypes and cross-reactivity of IgG antibodies to the corresponding MSP1₁₉ polypeptides (14, 43), block 15 to 16 polymorphisms underlying the variation in MSP1₃₃ and its impact on naturally acquired T-cell immunity are less well understood. The objectives of the current study were to evaluate MSP1₃₃ polymorphism in an area of western Kenya in which malaria is holoendemic and the corresponding allele specificity of IFN-γ responses by adults with naturally acquired immunity to malaria.