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S Whittaker

Publications and source records attributed to S Whittaker.

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

Minimizing adverse side-effects of oral bexarotene in cutaneous T-cell lymphoma: an expert opinion.

Bexarotene is an oral retinoid therapy that is effective for the treatment of early and advanced-stage cutaneous T-cell lymphoma (CTCL) in patients who have failed on other therapies. However, bexarotene treatment is associated with unavoidable side-effects, in particular hypertriglyceridaemia and hypothyroidism, which are manageable with adequate concomitant medications and are reversible on cessation of treatment. A pragmatic strategy for minimizing bexarotene-associated hypertriglyceridaemia and hypothyroidism is suggested, based on data from the studies with bexarotene in CTCL and on day-to-day experience with this agent in the clinical setting. The strategy anticipates that these common adverse events are likely to occur and recommends the early use of preventive therapy to lower triglycerides and elevate thyroid hormone levels in the blood, followed by subsequent monitoring, dose adjustment during bexarotene treatment, and titration of the daily bexarotene dose from 150 to 300 mg m(-2), which is optimal for most patients. When further information becomes available on how bexarotene interacts with lipid metabolism and thyroid function, the management approach suggested here may need to be changed.

Anticarcinogenic Agents↗
PubMed2006

Necrobiotic xanthogranuloma with paraproteinaemia.

Necrobiotic xanthogranuloma is a rare cutaneous condition that can be mistaken for atypical necrobiosis lipoidica. It has a strong association with a paraproteinaemia, which may progress to frank haematological malignancy. We describe four patients with variable cutaneous features, and their treatment response.

Aged↗
PubMed2006

Multicentric Castleman's disease in a patient with HIV.

Multicentric Castleman's disease (MCD) was originally described in non-HIV patients. It is a rare lymphoproliferative disorder, which is more commonly seen in HIV-positive patients and is associated with human herpes virus-8 (HHV-8). We describe a patient with advanced HIV who responded well to conventional highly active antiretroviral treatment. She was diagnosed with MCD soon after her diagnosis of HIV. She presented with multiple flares of her MCD. The case illustrates the difficulty of differentiating between episodes of septicaemia and a flare of MCD. The patient was treated with various chemotherapy regimens, which included several cycles of liposomal doxyrubicin and etoposide. There is currently no consensus on the treatment of MCD and various therapies are described in the literature, which include chemotherapy. Chemotherapy must be chosen with the immunosuppressive effects of the treatment being considered with caution. Both doxyrubicin and etoposide are well tolerated and successfully controlled the symptoms of MCD in our patient.

Adult↗
PubMed2005

Association between polymorphisms of the GPX1 gene and second primary tumours after index squamous cell cancer of the head and neck.

We investigated the association between genetic polymorphisms in GPX1 gene amongst patients who had index squamous cell carcinoma (SCCHN) and a second primary tumour (SPT) after a primary SCCHN in a case-control study. GPX1 genotypes were determined for 61 patients with SPT and for 259 control subjects by a PCR technique using a fluorescent-labelled primer. Analysis was by an ABI automated fluorescent sequencer. The associations between specific genotypes and the development of SPT were examined by logistic regression. A significant difference was found between the control group and the SPT cases in allele frequencies of GPX1 ALA( *)6 and ALA( *)7 (p(trend)=0.04). These results suggest that polymorphisms in the GPX1 gene may be a marker for SPT development and further studies are indicated.

Adult↗
PubMed2002

EORTC cutaneous lymphoma task force. European Organisation for Research and Treatment of Cancer.

The Cutaneous Lymphoma Task Force has represented the European Organisation for Research and Treatment of Cancer (EORTC) over the last two decades and has received worldwide acceptance and the highest respect. The group has been able to bring together the world's experts in this field to try to solve the basic problems associated with primary lymphomas of the skin and to create a productive scientific research basis. The definition and the classification of the disease per se has been a major controversial problem and the development of an EORTC classification for primary cutaneous lymphoma has been one of the main goals of the group. The purpose of this paper is to highlight and to provide a historical perspective regarding the contribution of the EORTC Cutaneous Lymphoma Group to the development of consensus guidelines for securing uniform diagnosis, classification and management of the heterogeneous group of primary cutaneous lymphomas. Some future perspectives and strategies of the group are also presented.

Achievement↗
PubMed2002

Psoriasis: response to high-dose intravenous immunoglobulin in three patients.

Treatment of recalcitrant psoriasis and psoriatic arthritis can be challenging, with treatment options limited by drug intolerance or poor efficacy. High-dose intravenous immunoglobulin (hdIVIg) has been used successfully in Kawasaki's disease and idiopathic thrombocytopenic purpura, where it has become the standard treatment. The literature also suggests its positive effect in the treatment of dermatological conditions, such as autoimmune chronic urticaria, atopic dermatitis, scleromyxoedema, dermatomyositis and autoimmune bullous disorders. We report three patients with treatment-resistant psoriasis and psoriatic arthritis who improved with hdIVIg.

Adult↗
PubMed2001

Prognostic significance of tumor burden in the blood of patients with erythrodermic primary cutaneous T-cell lymphoma.

Erythrodermic cutaneous T-cell lymphoma (CTCL) includes patients with erythrodermic mycosis fungoides who may or may not exhibit blood involvement and Sézary syndrome and in whom hematological involvement is, by definition, present at diagnosis. These patients were stratified into 5 hematologic stages (H0-H4) by measuring blood tumor burden, and these data were correlated with survival. The study identified 57 patients: 3 had no evidence of hematologic involvement (H0), 8 had a peripheral blood T-cell clone detected by polymerase chain reaction (PCR) analysis of the T-cell receptor gene and less than 5% Sézary cells on peripheral blood smear (H1), and 14 had either a T-cell clone detected by Southern blot analysis or PCR positivity with more than 5% circulating Sézary cells (H2). Twenty-four patients had absolute Sézary counts of more than 1 x 10(9) cells per liter (H3), and 8 patients had counts in excess of 10 x 10(9) cells per liter (H4). The disease-specific death rate was higher with increasing hematologic stage, after correcting for age at diagnosis. A univariate analysis of 30 patients with defined lymph node stage found hematologic stage (P =.045) and lymph node stage (P =.013) but not age (P =.136) to be poor prognostic indicators of survival. Multivariate analysis identified only lymph node stage to be prognostically important, although likelihood ratio tests indicated that hematologic stage provides additional information (P =.035). Increasing tumor burden in blood and lymph nodes of patients with erythrodermic CTCL was associated with a worse prognosis. The data imply that a hematologic staging system could complement existing tumor-node-metastasis staging criteria in erythrodermic CTCL.

Adult↗
PubMed2001

When the bough breaks: provider-initiated comprehensive care is more effective and less expensive for sole-support parents on social assistance.

This 5-year study conducted in Ontario, Canada is designed to assess the effects and expense of adding a mix of provider-initiated interventions to the health and social services typically used in a self-directed manner by sole-support parents and their children receiving social assistance in a national system of health and social insurance. Results from a 2-year interim analysis show that providing social assistance families with proactive comprehensive care (health promotion, employment retraining, and recreation activities for children) compared to allowing families to fend for themselves in a self-directed manner, results in 15% more exits from social assistance within 1 year and substantial savings to society in terms of social assistance payouts. It is no more expensive to provide health and social services in a comprehensive fashion, and equivalent reductions in parent mood disorder and child behavior disorders, as well as equivalent increases in parent social adjustment and child competence levels were also observed. This study presents clear evidence that providing comprehensive care to social assistance recipients produces tremendous short- and long-term financial gains and societal benefits.

Adolescent↗
PubMed2001

A case of adult T-cell leukaemia/lymphoma characterized by multiplex-fluorescence in situ hybridization, comparative genomic hybridization, fluorescence in situ hybridization and cytogenetics.

Adult T-cell leukaemia/lymphoma (ATLL) is a neoplasm of mature helper (CD4) T lymphocytes. Little is known, however, about the chromosome aberrations associated with the pathogenesis of this malignancy. Using molecular cytogenetic techniques we, therefore, investigated a 44-year-old man who had a 7-year history of ATLL with cutaneous involvement mimicking primary cutaneous T-cell lymphoma. Conventional cytogenetics revealed gross chromosomal changes with chromosome numbers ranging from 71 to 82. There were structural abnormalities of chromosomes 7 and 9, partial deletions of chromosomes 1, 3, 5 and 6, and loss of chromosomes 2, 4, 9, 11--14, 21 and 22. Multiplex-fluorescence in situ hybridization (M-FISH) identified two derivative chromosomes, der(6)t(6;7)(q16;q21) and der(7)t(6;7)(q16;q21)ins(6;12)(q2?;?), and a deletion of chromosome 1p. Conventional FISH confirmed the M-FISH findings. Comparative genomic hybridization of the blood revealed gains of DNA copy number at 1q12--25, 6p24--25, 9p23, 16p13--q13, 17q11--21, 19p13 and 20q13 and loss at 11p15 while lymph nodes showed gains at 3p22--24, 3q27--29, 7q36 and 15q26 and losses at 2p24--25, 2q37, 10p14--15, 11p15, 13q33--34 and 16p13.3. No DNA copy number changes were seen in a skin lesion. These results show the extent of genetic abnormalities within this malignancy.

Adult↗
PubMed2001

Evaluation of a new selective medium for methicillin-resistant Staphyloccocus aureus.

The aims of this study were to evaluate the performance of a new medium, desferrioxamine oxacillin tellurite egg-yolk mannitol salt agar (DOTEMSA) in detecting methicillin-resistant Staphylococcus aureus (MRSA) and then to compare this medium against the Public Health Laboratory Service (PHLS) recommendation of mannitol salt agar (Oxoid) with oxacillin (OMSA) and Baird-Parker medium with ciprofloxacin (BPC) for the isolation of MRSA. The individual selective agents contained in DOTEMSA were tested against isolates of coagulase-negative staphylococci (CNS) and the medium with all constituents was challenged with various bacteria. Routine screening specimens were plated out on OMSA, BPC and DOTEMSA and the plates were incubated and examined at 24 and 48 h. Tellurite, desferrioxamine and oxacillin each inhibited the majority of CNS isolates; only three (of 103) grew in the presence of all three agents. Sixty-two of 63 isolates of MRSA grew on DOTEMSA and 59 produced lipase. Most other bacteria were inhibited. In all, 184 MRSA isolates were isolated from 540 screening specimens. The sensitivity of OMSA, BPC and DOTEMSA was 42%, 81% and 51% at 24 h, and 60%, 89% and 89% at 48 h. At 48 h, the combination of BPC and DOTEMSA detected 99% of MRSA isolates. Seventy, 49 and one non-MRSA isolates needed investigation for each of the three media respectively. A proposed strategy for MRSA screening would use BPC and DOTEMSA, examining BPC at 24 h and both media at 48 h. Provisional reports could then be issued at 24 h on the basis of rapid agglutination tests to confirm isolates as S. aureus from BPC and at 48 h on the basis of typical colonies from DOTEMSA.

Cell Division↗
PubMed2001

Molecular genetics of cutaneous lymphomas.

The underlying molecular basis of primary cutaneous lymphomas has not yet been clarified. However, abnormalities of cell cycle control genes and well-defined tumor suppressor genes such as p53 are common and may contribute to disease progression and treatment resistance. Biallelic inactivation of tumor suppressor genes usually occurs by a combination of deletion, point mutation, and/or promotor hypermethylation. The detection of UVB-specific mutations of p53 requires confirmation but may have important implications for the management of patients with mycosis fungoides. Molecular cytogenetic studies have identified common regions of chromosomal deletion and amplification, which suggests the presence and location of genes that are of critical importance in the pathogenesis of cutaneous lymphoma.

Chromosome Aberrations↗
PubMed2001

Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival.

Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell depletion should be restricted to the CD4 subset.

Adult↗
PubMed2001

Service needs of families where one parent has an affective illness: implications for service, education, and policy.

This study explored the service needs of families with a parent with an affective illness. Focus-group and individual interviews were conducted at selected locations across Canada with individuals who had an affective disorder, their partners, and their adult children. A total of 67 participants were recruited. Corresponding service providers were mailed a questionnaire which asked information regarding these families' needs, the service provider's role with these families, and what prevented or assisted them in addressing those needs. A total of 419 service providers participated in the study. There was congruence between family-identified needs and the needs identified by service providers. However, there remains a large disparity between the knowledge of needs and having these needs met. The results of this study identify the gaps in service provision and make recommendations for changes in the areas of service, education, and policy-making.

Adult↗