bluuebunny/crossref_metadata_2025 huggingface dataset:
Amelioration of lupus manifestations by a peptide based on the complementarity determining region 1 of an autoantibody in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes of systemic lupus erythematosus (SLE) patients
Authors: MAUERMANN N , STHOEGER Z , ZINGER H , MOZES E
Published: August 2004

A peptide based on the complementarity determining region (CDR)1 of a human monoclonal anti-DNA autoantibody (hCDR1) was shown to either prevent or treat an already established murine lupus in systemic lupus erythematosus (SLE)-prone mice or in mice with induced experimental SLE. The present study was undertaken to determine the therapeutic potential of hCDR1 in a model of lupus in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes (PBL) of patients with SLE. To this end, PBL obtained from lupus patients were injected intraperitoneally into two equal groups of SCID mice that were treated either with the hCDR1 (50 µg/mouse) once a week for 8 weeks, or with a control peptide. Mice were tested for human IgG levels, anti-dsDNA autoantibodies, anti-tetanus toxoid antibodies and proteinuria. At sacrifice, the kidneys of the successfully engrafted mice were assessed for human IgG and murine complement C3 deposits. Of the 58 mice transplanted with PBL of SLE patients, 38 (66%) were engrafted successfully. The mice that were treated with the control peptide developed human dsDNA-specific antibodies. Treatment with hCDR1 down-regulated the latter significantly. No significant effect of the treatment on the levels of anti-tetanus toxoid antibodies could be observed. Treatment with hCDR1 resulted in a significant amelioration of the clinical features manifested by proteinuria, human IgG complex deposits as well as deposits of murine complement C3. Thus, the hCDR1 peptide is a potential candidate for a novel specific treatment of SLE patients.
Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls
Authors: ERIKSSON P , ANDERSSON C , EKERFELT C , ERNERUDH J , SKOGH T
Published: August 2004

Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1-like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL-18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL-18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American-European classification criteria. IL-18 and TGF-β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL-18 were related (R = 0·52, P = 0·0005). No relation was found neither between IL-18 versus IgG2, IgG3 or IgA, nor between serum TGF-β1 versus any of the immunoglobulins. Since serum levels of IL-18 are related to serum IgG1, IL-18 may be of importance for IgG1 switch and/or release.
Excitatory amino acids, TNF-α, and chemokine levels in synovial fluids of patients with active arthropathies
Authors: MCNEARNEY T , BAETHGE B A , CAO S , ALAM R , LISSE J R , WESTLUND K N
Published: August 2004

The aim of this study was to assess the synovial fluid (SF) neurotransmitter excitatory amino acid (EAA) levels, including glutamate (Glu) and aspartate (Asp), in the context of SF levels of other amino acids, TNF-α and chemokines from patients with active arthropathies. The SF was collected from patients with active rheumatoid arthritis (RA), gout, or osteoarthritis (OA). The SF samples were analysed for levels of neurotransmitters glutamate and aspartate, tumour necrosis factor-alpha (TNF-α), Regulated upon Activation Normally T-cell Expressed and Secreted (RANTES), macrophage inhibitory factor-1 alpha (MIP-1α) and interleukin 8 (IL-8). SF WBC counts were also determined. Correlations between SF EAA, TNF-α and chemokines were determined by the Pearson product-moment correlation. Primary cultures derived from SF from active RA and gout patients were incubated with added l-glutamate, to assess if exposure to Glu could increase TNF-α levels. There were significant elevations in SF EAA, SF TNF-α and SF RANTES in RA patients compared to gout or OA patients. Significant correlations between SF EAA and SF RANTES, MIP-1α and IL-8 levels were seen, and SF EAA and SF TNF-α or SF WBC levels approached significance. Addition of exogenous neurotransmitter glutamate significantly increased TNF-α levels in primary cell cultures derived from RA and gout patients. The SF neurotransmitter EAA levels significantly correlated to selected SF chemokine levels, in clinically active RA, gout and OA patients, independent of disease. Added Glu resulted in significantly increased TNF-α levels in primary synovial cell cultures. These data expand the relationship of SF neurotransmitter EAA levels to SF cytokines and chemokines in patients with clinically active arthritis, and suggest that neurotransmitters Glu and Asp contribute to peripheral inflammatory processes.
Cytokine expression pattern in the genital tract ofChlamydia trachomatispositive infertile women – implication for T-cell responses
Authors: REDDY B S , RASTOGI S , DAS B , SALHAN S , VERMA S , MITTAL A
Published: August 2004

Human genital infection caused by Chlamydia trachomatis is thought to be immunologically mediated, resulting in local recruitment of lymphocyte subsets and inducing the production of cytokines. Little information is available about the role of lymphocyte recruitment and the regulation of cytokine production in the genital tract of C. trachomatis positive infertile women. We have evaluated the recruitment of lymphocyte subsets in the genital tract and production of Th1/Th2 cytokines in cervical secretions and laparoscopic specimens from the fallopian tubes of C. trachomatis positive infertile women (n = 17) and compared them with controls, viz. C. trachomatis negative infertile women (n = 20) using ELISA and flow cytometry. None of these patients were found to be infected either with Candida sps., bacterial vaginosis, Trichomonas vaginalis, Neisseria gonorrhoeae, Mycoplasma hominis or Ureaplasma urealyticum in the cervix. Flow cytometric analysis of cervical secretions in Chlamydia positive women revealed recruitment of both CD4 and CD8 lymphocytes to the genital tract was up-regulated and a variation in the production rates of different cytokines in cervical secretions and fallopian tube was observed. We found that the immune responses in cervical secretions were of Th0 type, since all the analysed cytokines, viz. IFN-γ, TNF-α, IL-10 and IL-12 were up-regulated. As, both CD4 and CD8 cells contribute to the production of IFN-γ and IL-10, these results suggest that along with CD4 cells, CD8 lymphocytes also may be important for local regulation of Th1/Th2 responses in the genital tract during C. trachomatis infection.
Human macrophages kill human mesangial cells by Fas-L-induced apoptosis when triggered by antibody via CD16
Authors: BOYLE J J
Published: August 2004

Glomerulonephritis may be triggered by antibody deposits that activate macrophages to promote tissue damage. Macrophage-induced apoptosis of human vascular smooth muscle cells and rodent mesangial cells is potentially relevant to glomerulonephritis. Therefore, studies of macrophage-induced apoptosis were extended to antibody-activated macrophages. That is, we studied antibody dependent cellular cytotoxicity (ADCC). To corroborate results, we studied biochemical versus microscopic measurements, soluble or immobilized immunoglobulin and vascular smooth muscle cells (VSMCs) or mesangial cells (MCs). U937 macrophages and human peripheral blood macrophages provoked antibody-dependent killing of MCs and VSMCs. Macrophage-induced death was apoptotic based on electron microscopy, annexin-V, activated caspase-3 and hypodiploid DNA. ADCC was inhibited by antagonistic antibodies to Fas-L and to CD16 (Fc-γ-RIII) but not to CD64 (Fc-γ-RI). In conclusion, antibody-dependent killing of human MCs by human macrophages was via Fas-L and CD16.
Methotrexate reduces antibody responses to recombinant humanα-galactosidase A therapy in a mouse model of Fabry disease
Authors: GARMAN R D , MUNROE K , RICHARDS S M
Published: August 2004

Therapeutic enzymes are often recognized as foreign by the immune system of patients undergoing enzyme replacement therapy. The antibodies that develop may alter pharmacokinetics and biodistribution of the therapeutic protein, may be able to neutralize the activity of the enzyme, or may cause immune reactions in certain patients. We have explored treatment regimens to reduce the antibody response to human α-galactosidase A (r-hαGAL) in Fabry (αGAL knock-out) and normal BALB/c mice. A wide variety of treatment modalities were tested, including high dose tolerance induction, increased frequency of therapeutic doses and immunosuppressive drugs in combination with administration of enzyme. The most substantial effects were observed in mice injected intravenously with r-hαGAL in combination with methotrexate (MTX), which significantly lowered r-hαGAL-specific serum antibody levels. A short course of treatment with MTX was able to reduce antibody and spleen cell proliferative responses to long-term r-hαGAL treatment. MTX was able to suppress the development of r-hαGAL-specific IgG in antigen-primed mice. However, MTX was not effective in dampening robust ongoing antibody responses. These experiments provide a framework for the design of clinical protocols to prevent the drug-specific antibody responses of patients undergoing enzyme replacement therapy.
Interactions among human immunodeficiency virus (HIV)-1, interferon-γand receptor of activated NF-κB ligand (RANKL): implications for HIV pathogenesis
Authors: FAKRUDDIN J M , LAURENCE J
Published: August 2004

We reported recently that exposure of human T cells to soluble HIV-1 envelope glycoprotein gp120 induced biologically active tumour necrosis factor (TNF)-α-related cytokine receptor of activated NF-κB ligand (RANKL), the primary drive to osteoclast differentiation and bone resorption. Furthermore, certain anti-HIV protease inhibitors linked clinically to accelerated bone loss in HIV disease blocked the physiological control of RANKL activity by interferon (IFN)-γ through inhibition of degradation of the RANKL nuclear adapter signalling protein, TNF receptor associated protein 6 (TRAF6). We now report a series of reciprocal interactions among HIV-1, RANKL and IFN-γ. RANKL augmented HIV replication in acutely and chronically infected cells of T lymphocyte and monocyte lineage, effects which occurred at a transcriptional level in conjunction with activation of NF-κB. TNF-α and RANKL were markedly synergistic in induction of HIV. Low pharmacological levels of IFN-γ (0·75–3 ng/ml) suppressed RANKL-driven enhancement of HIV replication, as did L-T6DP-1, a cell-permeable peptide inhibitor of TRAF6. In contrast, HIV replication induced by TNF-α and phorbol ester were not inhibited, and in some cases augmented, by IFN-γ. We conclude that a positive feedback loop exists between RANKL production and HIV replication, which may be relevant to both the pathophysiology of HIV-linked osteopenia and control of HIV growth. This pathway appears distinct from those of other cytokine activators of HIV, with respect to its utilization of TRAF6 and its suppression by IFN-γ. These data raise the possibility that TRAF-specific inhibitory peptides, alone or in conjunction with IFN-γ, could be used to regulate HIV activation in vivo.
Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system
Authors: TEJDE A , MATHSSON L , EKDAHL K N , NILSSON B , RÖNNELID J
Published: August 2004

Immune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fcγ RII antibodies, whereas Fcγ R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction.
Interleukin-16 expression and release in bullous pemphigoid
Authors: FREZZOLINI A , CIANCHINI G , RUFFELLI M , CADONI S , PUDDU P , DE PITÀ O
Published: August 2004

Cutaneous infiltration of activated CD4+ T cells and eosinophils is an early event in blister formation during bullous pemphigoid (BP), suggesting that the trafficking of circulating leucocytes through the sites of inflammation, their activation and cytokine release is crucial in the pathogenesis of the disease. IL-16 is a major chemotactic factor able to recruit CD4+ cells in the skin during inflammation and to induce the expression of functional high-affinity interleukin (IL)-2 receptors, thus contributing to cellular activation and proliferation. We performed a study in order to evaluate the presence of IL-16 in skin samples and sera and blister fluids of patients affected with BP in active phase of the disease (n = 39), compared with healthy donors studied as control group. Ten patients were also evaluated before and after steroid therapy. Our results demonstrated that IL-16 was expressed strongly by keratinocytes and by dermal infiltrating CD4+ T lymphocytes in lesional skin of BP patients. High levels of IL-16 were detected in sera and blisters of BP, significantly higher in respect to healthy donors. When patients were investigated for the presence of eosinophil cationic protein (ECP) and soluble CD30 (sCD30) to reveal signs of eosinophils and Th2-cells activation, we found a positive correlation between IL-16 serum levels and both ECP and sCD30, suggesting that IL-16 is involved in Th2 lymphocytes and eosinophils recruitment during BP.
Children with chronic renal failure have reduced numbers of memory B cells
Authors: BOUTS A H M , DAVIN J C , KREDIET R T , MONNENS L A H , NAUTA J , SCHRÖDER C H , VAN LIER R A W , OUT T A
Published: August 2004

Reduced serum IgG and subclass levels have been demonstrated in children with chronic renal failure. To study possible causes of this reduction, we analysed B cell subset composition, T helper cell frequencies and immunoglobulin (Ig) production capacity in vitro in children with chronic renal failure, with or without dialysis treatment. B cell subsets were characterized by determining CD27, IgM, IgD and CD5 expression within the CD19+ population. Intracellular expression of interferon (IFN)-γ, interleukin (IL)-2 and IL-4 in PMA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) was used to evaluate T helper frequencies. The capacity of B cells to secrete Ig in vitro was determined by measuring IgG1, IgG2 and IgM in culture supernatants of anti-CD2/CD28 monoclonal antibody (MoAb)- or SAC/IL-2-stimulated PBMC. Memory B cell numbers (identified as percentage or absolute number of CD19+ IgM¯IgD¯ or CD19+CD27+ lymphocytes) were lower in children treated with haemodialysis (HD), peritoneal dialysis (PD) and children with chronic renal failure before starting dialysis treatment (CRF) compared to healthy controls (HC) (P < 0·05). Compared with HC, CD5+ (naive) B cells were reduced in HD-treated patients but not for PD or for children with chronic renal failure before starting dialysis treatment (CRF). No significant differences in CD4+ T helper cell subsets were found between the groups. However, CRF children had a higher percentage of IFN-γ producing CD8+ T lymphocytes compared to HC (P = 0·02). Finally, IgG1, IgG2 and IgM production in vitro was similar in the four groups. In conclusion, significantly lower numbers of memory type B cells were found in children with chronic renal failure compared to healthy controls. This reduction may contribute to the low Ig levels found in these children.
B cell epitope specificity in ANCA-associated vasculitis: does it matter?
Authors: VAN DER GELD Y M , STEGEMAN C A , KALLENBERG C G M
Published: August 2004

Pauci-immune idiopathic small-vessel vasculitis is strongly associated with the presence of antineutrophil cytoplasm autoantibodies (ANCA). Antibodies to PR3 predominate in patients with Wegener's granulomatosis; antibodies to myeloperoxidase (MPO) are found more frequently in patients with microscopic polyangiitis. There is increasing in vivo and in vitro evidence for a pathogenic role of ANCA in systemic vasculitis based on associations of ANCA with disease activity. If ANCA are pathogenic, why is the course of disease different from one patient to another? Antibodies can recognize different binding sites (epitopes) on their corresponding antigens. Differences in binding specificity may influence the pathogenic potential of the antibodies. Differences between epitope specificity of ANCA between patients or changes in epitope specificity of ANCA in time in an individual patient may, accordingly, result in differences in disease expression. This review will focus on epitope specificity of autoantibodies in systemic autoimmune diseases and especially on the epitope specificity of PR3– and MPO–ANCA. We will discuss whether PR3–ANCA or MPO–ANCA recognize different epitopes on PR3 and MPO, respectively, and whether the epitopes recognized by ANCA change in parallel with the disease activity of ANCA-associated vasculitis. Finally, we will speculate if the direct pathogenic role of ANCA can be ascribed to one relapse- or disease-inducing epitope. Characterization of relapse- or disease-inducing epitopes bound by PR3–ANCA and MPO–ANCA is significant for understanding initiation and reactivation of ANCA-associated vasculitis. Elucidating a disease-inducing epitope bound by ANCA may lead to the development of epitope-specific therapeutic strategies.
Lower concentration of serum soluble CD8 in severe Hashimoto's disease
Authors: YAMAMOTO N , WATANABE M , MATSUZUKA F , MIYAUCHI A , IWATANI Y
Published: August 2004

To investigate the roles of soluble CD4 (sCD4) and CD8 (sCD8) in the severity of autoimmune thyroid diseases, we examined serum concentrations of sCD4 and sCD8 in various degrees of severity of Hashimoto's disease (HD) and Graves’ disease (GD) by enzyme immunoassay. The serum concentration of sCD8 was lower in euthyroid patients with HD undergoing treatment for hypothyroidism (severe HD) than in untreated, euthyroid patients with HD (mild HD), but the sCD4 concentration did not differ between patients with severe and mild HD. The serum sCD8 concentration was negatively correlated with the proportion of CD25+ cells in CD8+ cells in patients with severe HD. Serum sCD4 and sCD8 concentrations did not differ between euthyroid patients with GD in remission and those with intractable GD. These results indicate that serum sCD8 is involved in the severity of HD, possibly by down-regulating the function of cytotoxic T cells.
Effect of tamoxifen on serum IL-18, vascular endothelial growth factor and nitric oxide activities in breast carcinoma patients
Authors: COSKUN U , GUNEL N , SANCAK B , ONUK E , BAYRAM M , CIHAN A
Published: August 2004

Vascular endothelial growth factor (VEGF) is a multi-functional cytokine that has been suggested to be a major angiogenic factor in breast cancer. Nitric oxide (NO) is a potent biological molecule that partipicates in the multi-step process of carcinogenesis. Interleukin (IL)-18 has been shown to have potent anti-tumour effects. In this study, we investigated the effect of tamoxifen therapy on serum VEGF, NO and IL-18 activity in breast cancer patients. Serum levels of VEGF, nitrate + nitrite and IL-18 were measured in 34 postmenopausal breast cancer patients before and 3 months after the tamoxifen therapy. Both serum VEGF and IL-18 levels decreased after tamoxifen therapy (P = 0·051, P < 0·05, respectively). Serum VEGF levels increased in patients with endometrial thickness, while patients without endometrial thickness had a significant reduction in serum VEGF levels after therapy (P < 0·05). Serum nitrate + nitrite levels increased after the therapy, but this was not statistically significant (P > 0·05). A decrease in serum VEGF levels with tamoxifen therapy may be a reflection of reduced angiogenic activity in patients without endometrial thickness. The negative effect of tamoxifen therapy on IL-18, which is known to have a potent antitumour activity, may be related to the decreased tumour growth by induction of NO and reduction of VEGF activity as a feedback mechanism.
Prevalence of SAP gene defects in male patients diagnosed with common variable immunodeficiency
Authors: EASTWOOD D , GILMOUR K C , NISTALA K , MEANEY C , CHAPEL H , SHERRELL Z , WEBSTER A D , DAVIES E G , JONES A , GASPAR H B
Published: August 2004

The molecular basis of common variable immunodeficiency (CVID) is undefined, and diagnosis requires exclusion of other diseases including X-linked lymphoproliferative disease (XLP). This rare disorder of immunedysregulation presents typically after Epstein–Barr virus infection and results from defects in the SAP (SLAM associated protein) gene. SAP mutations have been found in a few patients diagnosed previously as CVID, suggesting that XLP may mimic CVID, but no large-scale analysis of CVID patients has been undertaken. We therefore analysed 60 male CVID and hypogammaglobulinaemic patients for abnormalities in SAP protein expression and for mutations in the SAP gene. In this study only one individual, who was found later to have an X-linked family history, was found to have a genomic mutation leading to abnormal SAP cDNA and protein expression. These results demonstrate that SAP defects are rarely observed in CVID patients. We suggest that routine screening of SAP may only be necessary in patients with other suggestive clinical features.
HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy
Authors: RESINO S , GALÁN I , PÉREZ A , LEÓN J A , SEOANE E , GURBINDO D , ÁNGELES MUÑOZ-FERNÁNDEZ M
Published: August 2004

The objective of this study was to monitor the changes in the immune system of HIV-infected children with moderate or severe immunodeficiency after highly active antiretroviral therapy (HAART), comprising a follow-up study in 14 HIV-infected children on HAART at two time points separated approximately by 11·8 ± 0·4 (9·9; 15·4) months. HIV-infected children had significantly lower TREC levels than the control group, but 1 year after HAART the levels increased significantly (P < 0·05). In contrast, viral load (VL) did not change significantly. A positive correlation between T cell receptor excision circle (TREC) levels and both CD4+ T cell absolute counts (r = 0·558; P = 0·05) and percentages (r = 0·625; P = 0·030) was found. During follow-up on HAART, the percentages and absolute counts of naive CD4+ and CD8+ T cell subsets were increased significantly (P < 0·05). CD4+ CD45RAhi+ CD62L+, CD4+ CD45RA+ and CD4+ CD38+ percentages, and the CD8+ CD45RAhi+ CD62L+ counts reached similar values to the control group. Also, CD8+ CD45RO+ CD38+ and CD8+ CD45RO+ percentages, and CD8+ CD45RO+ CD38+ absolute counts (P < 0·05) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-α and interferon (IFN)-γ production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (P < 0·001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG1 and IgG3 plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin.
Telecytology in Hokkaido Island, Japan: results of primary telecytodiagnosis of routine cases
Authors: Yamashiro K. , Kawamura N. , Matsubayashi S. , Dota K. , Suzuki H. , Mizushima H. , Wakao F. , Azumi N.
Published: August 2004

In 1997, an Internet‐based static image telepathology system was built at Sapporo National Hospital, Japan. We can exchange high‐resolution microscopical images through a file transfer protocol server and discuss cytological findings and diagnosis on an electronic mailing list. We applied the system to primary telecytodiagnosis. From May 1997 to April 1999 we have made diagnoses of 614 daily cases only by looking at the video monitor images transmitted from the cytotechnologist of Wakkanai Municipal Hospital 300 km distant from Sapporo. The concordance between telecytodiagnosis and glass slide diagnosis was 88.6%. Kappa statistics for cervical smears was 0.919 and that for specimens other than uterine cervix was 0.810. The accuracy of telecytodiagnosis was 91.4%, and was not substantially different from that of the conventional mail‐based cytology in a previous year. We had five cases with a severely inappropriate diagnosis in telecytology, all of which however were quickly corrected by follow‐up histological or cytological specimens. With the use of an electronic mailing list the participants had quick and sufficient discussions. We conclude that telecytology is very useful for primary cytodiagnosis in regional medicine and that it may raise the accuracy of cytodiagnosis in future, if we make consistent efforts to reflect the benefits of telecytology in daily practices. This is the first report of clinical results of telecytology from Japan.
Benign follicular thyroid lesions versus follicular variant of papillary carcinoma: differentiation by architectural pattern
Authors: El Hag I. A. , Kollur S. M.
Published: August 2004

Differentiation between benign and malignant follicular lesions is one of the difficult diagnostic areas in thyroid fine needle aspiration (FNA). Nuclear criteria are usually used to distinguish between them. In this study the microarchitectural pattern of common benign follicular lesions, namely nodular hyperplasia (NH) and follicular adenoma (FA) were analysed in comparison with those of follicular variant of papillary carcinoma (FVPC) in order to aid in their differentiation. The FNA smears of histologically proven cases of FVPC, NH and FA were reviewed and compared. The microarchitectural features of FVPC, NH and FA were described. Three cytological features – multi‐layered rosettes, branching monolayered sheets and balls of thick pinkish colloid – were exclusively observed in FVPC. Hyperplastic papillae with intact follicles and colloid were frequently seen in NH, 83% and 100%, respectively. Albeit less frequently, they were also noted in FVPC, 25% and 75% of cases, respectively. These overlapping features make the distinction between FVPC and NH sometimes difficult; however, assessing the smears for the specific features of FVPC may help in their differentiation. None of the aforementioned microscopic findings with the exception of the seldom presence of colloid were documented in FA. The crowded clusters of follicular cells were seen both in FA and FVPC; however, they were complex and branching in the latter and round to oval in the former. Finally, smears with good recovery of material are indispensable for the identification of these helpful microarchitectural patterns.
Benign glandular cells in posthysterectomy vaginal smears: the incidence is higher than expected
Authors: Eren F. , Savci D. , Erbarut İ. , Gökaslan H.
Published: August 2004

In this study, we have investigated the frequency and clinical significance of glandular cells in posthysterectomy vaginal smears. The slides of vaginal cuff smears of 290 patients were reviewed. The glandular cells were categorized into three groups: (1) squamous metaplastic‐like cells; (2) columnar endocervical‐like cells; and (3) small round cuboidal cells. Glandular cells were found in 39 (13%) of the 290 vaginal smears. Group 1 type cells were seen in 76% (n = 30), group 2 type cells in 38% (n = 15) and group 3 type cells in 47% (n = 19) of the smears. In 19 (48%) of the smears combination of two or three groups were seen. The presence of glandular cells showed a strong association with inflammation/repair as a background finding in the smears. No correlation could be found between the presence of atrophy and history of chemotherapy or radiotherapy. Apart from these there was a prominent increase in reporting benign glandular cells after the application of the current Bethesda 2001 reporting criteria in our laboratory. As a result our study showed that the finding of glandular cells in posthysterectomy vaginal smears is more frequent than expected and most of them could be related to inflammatory and regenerative processes in the absence of a clearly identified underlying cause.
A retrospective clinical audit of cervical smears reported as ‘glandular neoplasia’
Authors: Kirwan J. M. , Herrington C. S. , Smith P. A. , Turnbull L. S. , Herod J. J. O.
Published: August 2004

The aims of this study were to review the diagnostic pathway of women with smears reported as ‘glandular neoplasia’ and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5‐year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as ‘glandular neoplasia’, 67 were reported as consistent with cervical glandular intra‐epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an ‘endometrial adenocarcinoma’ smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended.
Direct booking colposcopy clinic — the Portsmouth experience
Authors: Lukman H. , Bevan J. R. , Greenwood E.
Published: August 2004

We present 2 years data on direct booking in our colposcopy clinic. The new booking system has improved our efficiency and helped us to achieve the national quality standards on clinic waiting time. The non‐attendance (DNA) rate has also improved.
An audit of cervical smears reported to contain atypical glandular cells
Authors: Wilson C. , Jones H.
Published: August 2004

The terminology and classification system for the reporting of cervical smears is currently under review. However, evidence on which to base the reporting of atypical cervical glandular cells is lacking. This audit of glandular atypia reporting in cervical smears provides evidence to support a three‐tier sub‐classification system for cervical glandular atypia. The three sub‐classifications are distinct with respect to their positive predictive values and to the cell type of the abnormality as confirmed by histology and therefore relate to further clinical investigation.
Glandular prediction: the pride and the prejudice
Authors: Waddell C.
Published: August 2004

For the cytologist and clinician alike, glandular lesions pose possibly the greatest challenge in cervical screening. Worldwide, with increasing confidence in cytological prediction, terminology is evolving. In the UK, with the adoption of liquid based methods, the technical aspects of cervical cytology are being addressed, it is now time to standardise our terminology in glandular reporting. Consideration of the cytological complexity, clinical needs and international protocols is essential in this endeavour.
Examining health visiting expertise: combining simulation, interview and observation
Authors: Bryans Alison N.
Published: August 2004

Background.  Resource constraints and the drive towards evidence‐based practice are currently prompting the review of health visiting services, which are a costly element of community health services in the United Kingdom. There is a shortage of evidence about effective domiciliary health visiting practice that can inform local and national decisions about developing and reforming this service.

Aims.  This paper is based on a study which aimed to articulate the health visiting expertise involved in recognizing and responding to client need during home visits. The paper describes the innovative, multi‐method approach used to articulate this expertise, and presents the rationale for this unusual approach.

Discussion.  The study used the complementary methods of a 20‐minute simulated visit to an actress‐client, a postsimulation focused interview and subsequent observation of actual home visits with 15 study participants. Data‐gathering took place between 2001 and 2002. The rationale, strengths and limitations of the methodology are discussed, and recommendations made for further development based on the work.

Conclusions.  The findings confirmed the utility of this unusual combination of methods, with their blend of control and naturalism, for articulating the knowledge and expertise which underpins assessment practice. Further research using a similar approach is recommended for the systematic examination of professional expertise in nursing and multi‐disciplinary contexts.
Expertise or performance? Questioning the rhetoric of contemporary narrative use in nursing
Authors: Nelson Sioban , McGillion Michael
Published: August 2004

Background.  In the early 1980s there emerged in nursing a self‐conscious and well‐articulated concern to articulate nursing's contribution to patient care. This has fostered the production of a large volume of practice narratives that today form the basis of professional self‐understanding. First‐person practice narratives are now widely used as the evidence base for nursing expertise, not only in their natural home, the world of interpretative research, but also in the bureaucratic‐judicial domain of professional regulation, health care organizations, trades unions and professional associations.

Aim.  The aim of this paper is to question the use of individual narrative accounts of nursing practice as evidence of nursing expertise.

Method.  We examine the model, method, and continuing consequences of these discursive formations of practice. First, we present a methodological discussion of how personal narratives are produced by the interplay between discourse and subjectivity. Second, we explore clinical narratives of expertise in the work of Patricia Benner and others to uncover the common template for contemporary narrative.

Discussion.  Narrative production in nursing has led to particular constructions, rather than free representations of practice. It is these particular constructions that we call into question. Rather than viewing these narratives as revelatory of nursing practice, we argue that they place a ‘spotlight’ on the individual actor – the nurse – with an absence of structural practice context.

Conclusion.  We make the case that treatment of these narratives as individual evidence of expertise fundamentally misunderstands their function and purpose, and reduces the constitution of nursing expertise to the performance of a palatable and highly desirable discourse for a nursing audience.
Teaching qualitative research: a metaphorical approach
Authors: Cook Stephen H. , Frances Gordon M.
Published: August 2004

Background.  In the Western tradition, drawing attention to the linguistic significance of analogy and metaphor can be traced back to the writings of the early Greek philosophers Plato and Aristotle. More recently, philosophers of science have drawn attention to the role of analogy and metaphor in the development of scientific theory. Also, linguists and psychologists now suggest that, in addition to being distinctive uses of language with various rhetorical functions, metaphors constitute fundamental processes of thought with basic epistemological functions.

Aim.  Drawing on numerous sources from outside the nursing literature, this paper seeks to show the implications of current theory relating to analogy and metaphor for nursing and educational practice. It also seeks to demonstrate, using a practical example, how this theory can be applied to the teaching of qualitative research.

Method.  Using reflection on our experiences of using analogy and metaphor in teaching the qualitative research process on a Master's degree programme, we assess the potential for using analogy and metaphor as a teaching strategy. This experience is also used to explore and discuss the wider implications of the use of analogy and metaphor in health and educational practices.

Discussion.  While analogies and metaphors can help students make creative and imaginative links between existing conceptual frameworks and those associated with new knowledge, thereby facilitating its assimilation, the use of analogy and metaphor remains an under‐researched area of nursing and educational practice. The cultural specificity of a metaphor does not necessarily prevent its usefulness cross culturally. The use of metaphor and analogy can also facilitate the injection of humour to a subject students frequently find ‘dry’ and intimidating.

Conclusion.  Analogies and metaphors are potentially powerful teaching and learning strategies. However, much is still not known about how they work at the cognitive level. Consequently, there is considerable scope for further research in this area in nurse education and clinical practice.
Child protection and public health: nurses’ responsibilities
Authors: Crisp Beth R. , Lister Pam Green
Published: August 2004

Background.  Health care workers have been recognized as having a key role in the protection and care of Scotland's children, particularly in respect of identification and detection of child abuse. Nurses, especially health visitors, are often the first professionals to suspect that child abuse has taken place. While previous research has found that health visitors have primarily perceived their role as that of providing support and advice to vulnerable families, there are pressures on them to fulfil a more narrow surveillance role. Concurrent with a lack of clarity about the role of health visitors in child protection, there has been increasing recognition that other nurses can also make an important contribution, including those who do not work directly with children.

Aims.  The aim of the study was to explore nurses’ understanding of their professional responsibilities in relation to child protection, and the potential for nurses to be involved in the protection of children from abuse.

Methods.  A qualitative interview‐based design was used, and 99 nurses working in an National Health Service trust in a Scottish city were interviewed, either individually or in groups, about their professional involvements in child protection issues. Interview data were subjected to thematic analysis.

Findings.  There was lack of consensus among interviewees about the nursing remit in child protection issues, particularly with respect to the extent to which nurses should actively seek to detect cases of child abuse. An emphasis on identification and detection was not easily accepted by many nurses, and was perceived by some to be a change from their more traditional role of supporting families, as well as being potentially in conflict with some public health responsibilities.

Conclusion.  In spite of the perception of some nurses that there is a sharp divide between child protection work and public health interventions, many of the child protection roles identified by nurses, such as supporting families, parenting education and service development, are clearly within the ambit of contemporary notions of public health. Furthermore, it is clear that there is a role in child protection for a much wider group of nurses than health visitors.
Nurses who work outside nursing
Authors: Duffield Christine , Pallas Linda O'Brien , Aitken Leanne M.
Published: August 2004

Background.  The desire to care for people, a family history of professional health care work, and security in career choice are documented reasons for entering nursing. Reasons for leaving include workload, unsafe work environments and harassment. The relationship between these factors and the time nurses spend in the profession has not been explored.

Aim.  This paper reports a study with people who have left nursing, to investigate why they became a nurse, how long they stayed in nursing, and their reasons for leaving.

Method.  A questionnaire was mailed to Registered Nurses currently working outside nursing, seeking respondents’ reasons for entering and leaving nursing, and perceptions of the skills gained from nursing and the ease of adjustment to working in a non‐nursing environment. Data analysis included descriptive statistics, exploratory and confirmatory factor analysis, correlational analysis and linear and multiple regression analysis.

Results.  A model incorporating the factors ‘altruistic reasons’, ‘default choice’ and ‘stepping stone’ explained 36·2% of the variance in reasons for becoming a nurse. A model incorporating the factors ‘legal and employer’, ‘external values and beliefs about nursing’, ‘professional practice’, ‘work life/home life’ and ‘contract requirements’ explained 55·4% of the variance in reasons for leaving nursing. Forty‐eight per cent of the variance in tenure in nursing practice was explained through personal characteristics of nurses (36%), reasons for becoming a nurse (7%) and reasons for leaving (6%).

Conclusion.  The reasons why nurses entered or left the profession were varied and complex. While personal characteristics accounted for a large component of tenure in nursing, those managing the nursing workforce should consider professional practice issues and the balance between work life and home life.
The organizational and performance effects of nurse practitioner roles
Authors: van Offenbeek Marjolein A.G. , Knip Marrig
Published: August 2004

Background.  Most studies evaluating the roles of Nurse Practitioners have compared the care delivered by individual Nurse Practitioners with that provided by other professionals. These studies should be complemented by research focusing on a higher unit of analysis, namely the organization of the care process for a specific patient group. The most important reason is that Nurse Practitioners are increasingly involved in direct, multiprofessional care in complex health care organizations and networks. In these work settings, their roles may, in both positive and negative ways, lead to changes in the organization of the entire care delivery system.

Aim.  The aim of this paper is to stimulate awareness and evaluation of these organizational changes and their potential impact on the effectiveness of the care process.

Approach.  A conceptual model based on patterned systems contingency theory is proposed. With the help of this model, attention is drawn to issues at the level of the organization and the effectiveness of the care processes that merit attention when Nurse Practitioner positions are being introduced. These issues are derived from case studies in Dutch hospitals.

Results.  According to the model, a Nurse Practitioner position will change the work structure of the care process involved. Therefore, the effectiveness of a Nurse Practitioner position will be dependent on the changes realized in the work structure. The resulting structure should fit the task characteristics of the care services demanded by the specific patient group. On the basis of this model and the examples presented, questions for further study are formulated.

Conclusions.  Nurse Practitioner roles can only enhance the effectiveness of care processes when embedded in a work structure that is internally consistent and adjusted to the task environment and available skill‐mix. A structural contingency framework may be helpful in identifying relevant organizational issues. To determine the effects of Nurse Practitioner roles, cross‐sectional as well as longitudinal studies are needed.
Schizophrenia: problems of separation in families
Authors: Jungbauer Johannes , Stelling Kirsten , Dietrich Sandra , Angermeyer Matthias C.
Published: August 2004

Background.  In the past, family relationships of people with schizophrenia have mainly been investigated from a clinical viewpoint. The perspective of family development has generally been overlooked in this area of research.

Aim.  This paper reports a study exploring problems of development and detachment in families with an adult child with schizophrenia.

Method.  Using in‐depth interviews, 51 parents of people with schizophrenia were questioned about their living situations and relationships with patients.

Findings.  Spatial separation from the family home was often complicated or even prevented entirely, with patients permanently living in their parents’ household or in the same neighbourhood. Many patients remained dependent on their parents’ emotional, practical and financial support. Typically, the parent–child relationship was re‐intensified, often with a concurrent loss of social contacts outside the family. From a biographical point of view, schizophrenia often caused problems for families by making parenthood permanent and lifelong parental support necessary. Many parents had to revise their expectations of both their ill child's development and their own personal plans.

Conclusion.  From the viewpoint of family psychology, schizophrenia is a serious obstacle to development that affects both patients and their parents. Family‐related support should increasingly take into account the issue of the difficult detachment of patients from their parents.