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R Russell-Jones

Publications and source records attributed to R Russell-Jones.

At least 19 recordsLinked to original sources
PubMed2006

Evidence-based practice of photopheresis 1987-2001: a report of a workshop of the British Photodermatology Group and the U.K. Skin Lymphoma Group.

Photopheresis or extracorporeal photochemotherapy (ECP) is a novel immunomodulatory therapy which involves separation of the patient's leucocyte-rich plasma, followed by ex vivo administration of a photosensitizer and ultraviolet A radiation, before reinfusion. ECP has been used successfully for the treatment of cutaneous T-cell lymphoma (CTCL: Sézary syndrome), graft-versus-host disease (GVHD) and cardiac transplant rejection. ECP has a dose-sparing effect on concurrent immunosuppressive therapy. The procedure induces apoptosis of the irradiated lymphocytes, but the exact mechanism by which ECP exerts its therapeutic effect in these different conditions is uncertain. The treatment has very few adverse effects and in particular is not associated with an increased incidence of opportunistic infections. The evidence for the efficacy of ECP has been appraised by a combined British Photodermatology Group and U.K. Skin Lymphoma Group workshop on the basis of evidence published up to the end of 2001 and on the consensus of best practice. There is fair evidence for the use of ECP in erythrodermic CTCL and steroid-refractory GVHD, but randomized controlled studies are needed. There is good evidence supporting the use of ECP in preventing cardiac rejection following transplantation. Randomized controlled trials have also shown a therapeutic benefit in type 1 diabetes mellitus, but the inconvenience associated with the procedure outweighed the clinical benefit. There is fair evidence not to use ECP for the treatment of systemic sclerosis and multiple sclerosis, and good evidence not to use ECP for other forms of CTCL.

Combined Modality Therapy↗
PubMed2006

Molecular staging of lymph nodes from 60 patients with mycosis fungoides and Sézary syndrome: correlation with histopathology and outcome suggests prognostic relevance in mycosis fungoides.

BACKGROUND: Histological evidence of lymph node involvement is associated with a poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To determine whether T-cell receptor (TCR) gene analysis is of prognostic relevance in CTCL. METHODS: TCR gene analysis was performed on lymph node specimens from 60 patients with mycosis fungoides (MF) and Sézary syndrome (SS) using a highly sensitive polymerase chain reaction (PCR)/single-strand conformational polymorphism analysis and results were correlated with skin, overall clinical and histological lymph node stages. RESULTS: The frequency with which a T-cell clone was detected in lymph node samples from patients with MF increased with skin stage, overall clinical stage and with the degree of histological involvement: six of 19 patients with uninvolved lymph nodes or limited histological involvement (LN0-2) and 13 of 14 patients with advanced histological involvement (LN3-4) had a detectable T-cell clone. In SS, 22 of 27 patients had a detectable lymph node T-cell clone. The clonal patients had a poorer prognosis than nonclonal patients (median survival from biopsy of > 72 months vs. 16 months for MF and 41.5 vs. 16.5 months for SS). Regression analysis confirmed that TCR gene analysis identifies a group of MF patients with a worse prognosis (P = 0.013). However, the molecular lymph node stage did not provide independent prognostic information in this cohort of patients in multivariate analysis. CONCLUSIONS: Molecular staging in MF and SS using a PCR-based method for TCR gene analysis provides additional information to histological examination. Specifically, this study identified a group of MF patients with early lymph node involvement with a poorer prognosis. However, a larger prospective study of patients with MF and early histological lymph node involvement is required to confirm whether molecular staging of lymph nodes provides independent prognostic information in a multivariate model.

Adolescent↗
PubMed2005

The use of LYVE-1 antibody for detecting lymphatic involvement in patients with malignant melanoma of known sentinel node status.

BACKGROUND: Sentinel node (SN) status is the most important prognostic indicator in patients with cutaneous melanoma without clinically evident metastatic spread, but the procedure is associated with considerable morbidity. The LYVE-1 lymphatic marker offers the possibility of studying lymphangiogenesis and tumour metastasis within the primary excision. AIMS: To establish whether lymphatic vessel numbers/distribution within the primary tumour correlated with SN status. To assess whether tumour cells were easily demonstrable within lymphatics and could be used as a surrogate for SN status. METHODS: Double immunostaining for LYVE-1 and S100 in cutaneous biopsies from 18 SN+ patients with no lymphatic/vascular involvement on routine histology and 18 SN- patients matched for tumour thickness and ulceration. RESULTS: Lymphatic vessels were detected in all cases. Vessels within the tumour mass were suggestive of active lymphangiogenesis; those outside were mainly mature vessels with well defined walls. Tumour cells within lymphatics were detected in one of 18 SN- and five of 18 SN+ patients. Lymphatics containing tumour cells were all outside the tumour mass in well formed vessels, suggesting melanoma cell invasion into preformed lymphatics. There was no significant difference in lymphatic counts between SN+ and SN- patients. Although peritumorous lymphatic counts were higher in ulcerated than non-ulcerated melanomas, they did not vary with Breslow thickness. CONCLUSION: LYVE-1 staining can reliably demonstrate lymphatic vessel distribution, but lymphatic counts cannot predict melanoma metastatic potential and cannot substitute for SN biopsy. LYVE-1 immunostaining can detect melanoma cells within lymphatics, but is unreliable in predicting melanoma metastasis, failing to detect metastatic spread in more than two thirds of patients with regional node metastasis.

Biomarkers, Tumor↗
PubMed2004

Syringotropic cutaneous T-cell lymphoma: an immunophenotypic and genotypic study of five cases.

There is uncertainty about the exact nosological relationship between mycosis fungoides, follicular mucinosis, syringolymphoid hyperplasia with alopecia (SLHA) and syringotropic cutaneous T-cell lymphoma (CTCL). We report the clinical, histological, immunophenotypic and genotypic characteristics of a series of five patients (three men and two women) with syringotropic CTCL. We also review the 15 cases of SLHA previously reported in the literature. We conclude that syringotropic CTCL is a distinct clinicopathological variant of mycosis fungoides which may present on its own with characteristic punctate erythema or more commonly in association with folliculotropic lesions. Syringotropic CTCL is characterized histologically by infiltration of sweat glands by atypical lymphocytes in association with syringolymphoid hyperplasia. Cases of SLHA represent a syringotropic form of CTCL in association with follicular involvement, and such cases need to be investigated using T-cell receptor gene analysis of both skin and blood. Only limited conclusions on prognosis can be derived from our preliminary data. However, a review of the literature suggests that the prognosis does not differ significantly from other types of mycosis fungoides of equivalent stage.

Adult↗
PubMed2004

BCL2 and JUNB abnormalities in primary cutaneous lymphomas.

BACKGROUND: BCL2 is upregulated in nodal and extranodal B-cell non-Hodgkin's lymphomas, with a consequent antiapoptotic effect. However, loss of BCL2 has also been noted in some malignancies, suggesting a different molecular pathogenesis. OBJECTIVES: To investigate genomic and protein expression status of BCL2 and to compare the results with that of JUNB in primary cutaneous lymphomas (PCLs). METHODS: We analysed gene copy number of BCL2 and JUNB in 88 DNA samples from 80 patients with PCL consisting of Sézary syndrome/mycosis fungoides (SS/MF), primary cutaneous B-cell lymphoma (PCBCL) and primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL) by the use of real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Real-time PCR and IHC findings were subsequently compared with the results of additional fluorescent in situ hybridization (FISH) analysis of 23 cases of SS and Affymetrix cDNA expression microarray study of two primary cutaneous T-cell lymphoma (CTCL) cell lines. RESULTS: Real-time PCR analysis showed loss of BCL2 gene copy number in 22 of 80 PCL cases (28%), including 17 of 42 SS/MF, three of 13 C-ALCL and two of 33 PCBCL samples, and gain of BCL2 in four PCBCL samples. Gain of JUNB was identified in 18 of 71 PCL cases (25%), including nine of 35 SS/MF, seven of 13 C-ALCL and two of 31 PCBCL samples. IHC analysis revealed absent nuclear expression of BCL2 protein in 47 of 73 PCL cases, comprising 28 of 36 SS/MF, eight of eight C-ALCL and 11 of 29 PCBCL cases. In contrast, BCL2 protein expression was detected in 26 of 73 PCL cases, consisting of 18 of 29 PCBCL and eight of 36 SS/MF cases. JUNB protein expression was present in tumour cells from 30 of 33 of SS/MF and eight of eight C-ALCL, and was absent in tumour cells from 18 of 27 PCBCL cases. A comparison between BCL2 and JUNB revealed loss of BCL2 and gain of JUNB in five of 35 SS/MF samples, and expression of JUNB protein and absent BCL2 expression in 25 SS/MF and eight of eight C-ALCL cases. In contrast, expression of BCL2 and absent JUNB expression were detected in 67% of PCBCL cases. Additional FISH analysis revealed deletion of BCL2 in 19 of 23 SS cases (83%), including eight cases with BCL2 loss shown by real-time PCR. Furthermore, Affymetrix expression microarray demonstrated decreased expression of proapoptotic and antiapoptotic genes involved in BCL2 signalling pathways such as BOK, BIM, HRK, RASA1 and STAT2 in two CTCL cell lines with BCL2 loss and absent BCL2 expression. Increased expression of JUNB was also identified in the MF cell line. CONCLUSIONS: These findings provide a comprehensive assessment of BCL2 and JUNB status in PCL, and suggest that there is a selection pressure in a subset of CTCL cases for tumour cells showing BCL2 loss and upregulation of JUNB primarily through chromosomal deletion and amplification, respectively.

Genes, bcl-2↗
PubMed2004

Topical imiquimod immunotherapy in the management of lentigo maligna.

Melanoma in situ of the lentigo maligna (LM) type is a precursor lesion of LM melanoma. It most commonly occurs in elderly individuals, on the head and neck. Although surgical excision is recommended, this may not be practical for large lesions at cosmetically sensitive sites. In addition, histological changes commonly extend beyond the clinical margins of the lesion. This study describes the use of imiquimod 5% cream as topical immunotherapy in the management of lentigo maligna. Twelve patients (average age 63 years, 10 female), of biopsy-proven facial LM were treated with topical imiquimod, three times a week for 6 weeks. In the absence of an inflammatory response, patients were asked to apply the treatment daily. Seven showed clearance of the LM clinically and histologically. A further three patients showed clearance histologically with persisting pigmentation due to dermal melanin and melanophages. Thus, 10 of 12 patients cleared with no relapse after a median follow-up of 6 months. Two patients failed to respond to imiquimod and their lesions were treated with surgical excision. Imiquimod was well tolerated, except in three patients who experienced an intense inflammatory response. Two of these also developed secondary infection. Imiquimod 5% cream appears to offer a potential noninvasive method for the treatment of lentigo maligna.

Adjuvants, Immunologic↗
PubMed2004

Co-existence of lichen amyloidosus and angiolymphoid hyperplasia with eosinophilia.

Summary Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vascular tumour. It presents with small, dull red papules or nodules usually on the ears and preauricular areas and only 20% of lesions are multiple. We report a case of multiple scattered lesions of ALHE in a patient who subsequently developed lichen amyloidosus. Cases of lichen amyloidosus in association with Kimura's disease have been reported previously, but there are no reports of lichen amyloidosus with ALHE. The coexistence of these two conditions implies that ALHE is an inflammatory disorder, as an inflammatory process resulting in basal layer damage is necessary for the occurrence of lichen amyloidosus.

Adult↗
PubMed2004

A randomized cross-over study to compare PUVA and extracorporeal photopheresis in the treatment of plaque stage (T2) mycosis fungoides.

PUVA is a well-established and effective treatment for plaque stage mycosis fungoides (MF) but its use is limited on a long-term basis because of the risk of cutaneous carcinogenesis. A further disadvantage is that nonexposed areas (sanctuary sites) often develop persistent disease. Therefore it is important to find alternative methods of treatment. Extracorporeal photopheresis (ECP) is a form of photochemotherapy that involves exposure of white blood cells to UVA with psoralens and can be effective in Sézary syndrome and erythrodermic cutaneous T-cell lymphoma. The aim of this study was to compare the efficacy of PUVA and ECP in the treatment of patients with T2 plaque stage (Stage 1B) MF who had a detectable peripheral blood T-cell clone. The study was of a cross-over design. Sixteen patients were randomized to receive either PUVA twice weekly for 3 months followed by ECP once monthly for 6 months at relapse, or vice-versa. Response was assessed by monthly skin scores and peripheral blood T-cell clonality. Ten patients received PUVA initially and six ECP initially. Eight patients completed the study. Skin scores taken at the completion of each treatment arm in patients who completed the study were 113 units better (confidence interval, 42-184 units) following 3 months PUVA than 6 months ECP (P = 0.002). Peripheral blood T-cell clones were detectable in all patients post-treatment. This study indicates that ECP is not effective in the treatment of plaque stage (1B/T2) MF even in patients with molecular evidence of a peripheral blood T-cell clone. Although PUVA was more effective than ECP, neither treatment modality cleared malignant T-cells from the peripheral blood.

Adult↗
PubMed2004

The effect of extracorporeal photopheresis on intracellular cytokine expression in chronic cutaneous graft-versus-host disease.

BACKGROUND: Cytokines derived from T helper (Th)1 lymphocytes are thought to be involved in the pathogenesis of graft-versus-host disease (GVHD) and extracorporeal photopheresis (ECP) has been reported to affect Th1/Th2 lymphocyte ratios. It may also influence the balance of cytotoxic Tcells (Tc1/Tc2). OBJECTIVES: This study was formulated to assess the effect of ECP on the cytokine profiles of peripheral blood (PB) lymphocytes from patients with chronic GVHD. PATIENTS AND METHODS: Nine patients were studied. Peripheral blood was sampled at baseline and between 3 and 4 months of therapy when clinical effects are demonstrable. Intracellular cytokine production was assessed in vitro by stimulating PB lymphocytes with phorbol-12-myristate 13-acetate (PMA), inhibiting cytokine release and staining with fluorescein-labelled monoclonal antibodies to interleukin (IL)-2, interferon gamma (IFN-gamma) and IL-4. Flow cytometry analysis gave the absolute number and the percentage of cells expressing a particular cytokine within each lymphocyte subset. RESULTS: Absolute counts of CD3, CD4, CD8, CD19 and CD16+ cells per microlitre were recorded before and after ECP. There was a small but non-significant reduction in all subsets after 3 months of ECP. The percentage of cells expressing IL-2 and IFN-gamma rose following ECP in both the CD4 and CD8 subsets. However, only the percentage of CD4 cells expressing IFN-gamma reached statistical significance (P = 0.02; 95% confidence interval, CI 0.6-15.6). There were no significant changes in the percentage of CD4 cells expressing IL-4. CONCLUSIONS: Our findings appear to be inconsistent with current theories regarding the pathogenesis of GVHD as increased production of Th1 or Tc1 cytokines might be expected to exacerbate GVHD. However, chronic GVHD is characterized by a relative deficiency of IL-2 and IFN-gamma producing cells compared with other patients post-bone marrow transplantation (BMT). This indicates that Th1 and Tc1 cytokines are depleted in chronic GVHD. Thus, by reducing disease activity, ECP could allow cytokine production by these cells to recover. This indicates that the therapeutic effect of ECP is mediated by a different mechanism, and that the changes observed in this study are epiphenomena.

Bone Marrow Transplantation↗
PubMed2003

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological, immunophenotypic and molecular analysis of six patients.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin. In the World Health Organization classification of T-cell and natural killer cell lymphoma it is listed as an example of extranodal lymphoma. In practice, however, it is most likely to present to a dermatologist. OBJECTIVES: To describe the clinicopathological, immunophenotypic and molecular features of six U.K. patients with SPTCL. METHODS: The clinical, histological and immunophenotypic features were reviewed. T-cell receptor (TCR) gene analysis was performed on blood and tissue samples using polymerase chain reaction/single-strand conformational polymorphism analysis of the TCR-gamma gene using consensus primers. In situ hybridization was performed on lesional skin to detect mRNA for Epstein-Barr virus (EBV). RESULTS: All patients presented with subcutaneous nodules, plaques or ulceration, and three had systemic symptoms. All biopsies exhibited an infiltrate of medium to large pleomorphic cells involving the subcutis with characteristic rimming of fat spaces. Five showed areas of necrosis, but only one showed marked cytophagia. In three cases the neoplastic cells did not express TCR-beta. One was strongly p53 positive, and the other two were CD56 positive. Both these patients showed epidermal involvement with lichenoid changes histologically, and both developed the haemophagocytic syndrome. The other three cases were TCR-beta positive, CD8 positive and CD56 negative. All cases were positive with pan T-cell markers and also for the cytotoxic granule protein T-cell intracellular antigen-1 and granzyme B. All cases were EBV negative both by immunostaining (latent membrane protein-1) and by in situ hybridization (EBV-encoded mRNA). TCR gene analysis revealed a T-cell clone in four of five cases; two of these patients had an identical T-cell clone in the peripheral blood. The median survival was 16 months. However, two of the three TCR-beta-negative patients have died, whereas none of the TCR-beta-positive patients has died. CONCLUSIONS: This is the first series of SPTCL patients to be reported in the U.K. and the data support the view that there are two subsets of SPTCL: those derived from gammadelta T cells which carry a poor prognosis, and are usually CD56 positive, and a more indolent group derived from alphabeta T cells.

Adult↗
PubMed2003

Blastic natural killer cell and extranodal natural killer cell-like T-cell lymphoma presenting in the skin: report of six cases from the UK.

BACKGROUND: Some lymphomas express natural killer (NK)-cell markers such as the neural cell adhesion molecule, which is recognized by the CD56 antibody. These lymphomas may present in the skin, but do not represent a homogeneous group. The new World Health Organization classification of lymphoma/leukaemia recognizes several types of NK/T-cell neoplasm, including blastic NK-cell lymphoma, which characteristically presents with cutaneous lesions. OBJECTIVES: To describe the clinical, pathological and molecular features in six cases of CD56+ lymphoma with cutaneous presentation. METHODS: The clinical, histopathological and immunophenotypic features of six patients were reviewed. In addition, in situ hybridization (ISH) to identify Epstein-Barr virus (EBV) mRNA, and polymerase chain reaction analysis to identify the presence of a clonal population of T cells or B cells were performed on lesional skin. RESULTS: All patients presented with widespread nodules and plaques, which in five cases were a characteristic purple colour. Four patients developed disseminated disease, three with neurological involvement. These four patients died between 14 and 46 months following diagnosis (median 30 months). In four of six cases the histopathological and immunohistological features were in keeping with a blastic NK-cell lymphoma. No clonal immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement was detected in the four cases consistent with an origin from NK cells. A further case fitted the criteria for an extranodal NK/T-cell lymphoma of nasal type and was also the only case to show evidence of EBV mRNA by ISH. A clonal T-cell population was identified in the final case. This patient also exhibited molecular evidence of a clonal B-cell population and a t(14;18) translocation confirmed by sequence analysis. CONCLUSIONS: Our data confirm that NK-cell lymphomas presenting in the skin are a heterogeneous group, and that in the U.K., blastic NK-cell lymphoma is more common than extranodal NK/T-cell lymphoma of nasal type. These lymphomas pursue an aggressive course, with rapid development of disseminated disease, and resistance to chemotherapy. Detailed immunophenotyping is needed to distinguish the different types. Our molecular data indicate that blastic NK-cell lymphoma cases lack clonal TCR/IgH gene rearrangements consistent with an NK-cell origin. Our ISH findings indicate that EBV plays a pathogenetic role only in extranodal NK/T-cell lymphoma of nasal type.

Adult↗
PubMed2003

Giant condyloma of Buschke-Loewenstein in association with erythroderma.

The Buschke-Loewenstein tumour is regarded as a type of verrucous carcinoma occurring on anogenital mucosal surfaces. The tumour is locally invasive but displays a benign cytology and rarely metastasizes. It is associated with human papillomavirus types 6 and 11. We describe a case of Buschke-Loewenstein tumour occurring in a 61-year-old man which behaved in a locally aggressive manner and was associated with human papillomavirus type 16 and erythroderma which proved resistant to treatment. The patient refused surgery and therapy with interferon alpha was ineffective. Chemotherapy with systemic cisplatin and 5-fluorouracil produced a partial response before the patient succumbed from gram-negative septicaemia.

Anti-Bacterial Agents↗
PubMed2003

Severe generalized argyria secondary to ingestion of colloidal silver protein.

Argyria is a rare cause of cutaneous discolouration caused by silver deposition. We report a case of dramatic and diffuse argyria secondary to ingestion of colloidal silver protein over a 1-year period. Stained electron microscopy with spectral analysis was used to confirm the clinical diagnosis. Silver-protein complexes are deposited in the skin and reduced to inert silver salts by sunlight in a process similar to that harnessed in photography. Our patient had obtained the silver for consumption via mail order. It had been advertised as a cure for a variety of diseases. Colloidal silver protein is commercially available as a 'food supplement', hence circumventing the strict controls placed on medicines.

Argyria↗
PubMed2003

Tea tree oil dermatitis associated with linear IgA disease.

Tea tree oil dermatitis is an increasingly common finding, reflecting the strong demand for natural remedies and aromatic substances. Linear immunoglobulin A (IgA) disease is a rare acquired subepidermal blistering disorder, characterized by basement membrane zone IgA deposition. We describe a patient in whom linear IgA disease appears to have been precipitated by a contact reaction to tea tree oil.

Adolescent↗