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G Stevens

Publications and source records attributed to G Stevens.

At least 19 recordsLinked to original sources
PubMed2006

Two-view mammography at the incident round has improved the rate of screen-detected breast cancer in Wales.

AIM: To investigate whether pre-invasive and invasive cancer detection rates were improved in Wales after the introduction of two views at incident screens. METHODS: The records of women attending follow-up screening for 2 years before and 2 years after the introduction of two-view incident screening were analysed. Cancer detection rates were compared before and after introduction of two view screening. RESULTS: At the incident round 98,752 women had one and 95,464 had two views. Five hundred and fifty-five cancers were detected with one view and 744 with two, an increased detection rate from 5.6 to 7.8 cancers per 1000 women screened (p=0.01). Two hundred and thirty-nine small cancers were detected with one view and 323 with two, increasing the detection rate from 2.4 to 3.4 per 1000 women screened (p=0.05). CONCLUSIONS: Two-view mammography at incident rounds detects more cancers and more favourable prognosis small cancers than single-view mammograms.

Breast Neoplasms↗
PubMed2005

Evaluation of healing by gentle touch.

OBJECTIVES: To evaluate the effectiveness and safety of healing by gentle touch in clients attending The Centre for Complementary Care (CCC) in Eskdale, Cumbria. STUDY DESIGN: An evaluation of data collected by questionnaire over 6 years. METHODS: All clients attending the CCC between 1995 and 2001 were invited to participate in this study, and data were collected from 300 subjects with a wide range of ailments who received four treatment sessions within 6 weeks. Exclusion criteria were: recent treatment at the CCC; failure to complete four treatment sessions; and age under 16 years. Outcome measures included comparison of pre- and post-treatment levels of physical (pain, disability, immobility, sleep disturbances, reliance upon medication, daily activities) and psychological (stress, panic, fear, anger, relaxation, coping, depression/anxiety) functioning; these were assessed using a questionnaire with visual analogue scales for subjective rating of symptoms and the EuroQoL (EQ-5D), a generic state-of-health measure. RESULTS: Wilcoxon signed ranks tests showed statistically significant improvements in both psychological and physical functioning, particularly in stress reduction (median stress levels fell by four points), pain relief (median pain ratings fell by two points), increased ability to cope (median improvement of three points) and increased general health ratings (median improvement of 20 points) between study entry and end of treatment (P < 0.0004 for all these symptoms). The most substantial improvements were seen in those with the most severe symptoms at study entry. No adverse effects of treatment were documented. CONCLUSIONS: This audit of treatment outcomes provides evidence consistent with the hypothesis that healing, as provided at the CCC, was associated with improved psychological and physical functioning in the majority of subjects, and is worthy of further evaluation.

Adolescent↗
PubMed2005

Importance of radiation time and dose factors on outcome for childhood medulloblastoma.

The purpose of this study was to investigate the relationship of posterior fossa radiation therapy duration (PFRTD) and relapse-free survival (RFS) following adjuvant craniospinal RT for childhood medulloblastoma. A retrospective audit was performed assessing all children aged <18 years managed with adjuvant craniospinal RT for medulloblastoma in Australia and New Zealand in 1980-1993. Children receiving prolonged (>180 days) pre-RT chemotherapy were excluded. Data were obtained for potential prognostic factors in domains of patient, tumour and treatment factors. Radiation therapy time factors assessed were PFRTD and time interval from surgery to commencement of RT (SRTD). The end-point assessed was RFS and analysis was performed using Cox regression and Kaplan-Meier survival. One hundred and eighty-nine children were identified from 10 oncology units, with data available from 182 children for analysis. Median follow up was 5.3 years. Seventy-three per cent of children presented with disease confined to the cerebellum; 13% had initial neuraxis disease. Macroscopic resection was described in 54%; 42% received adjuvant chemotherapy. Median RT dose and RT duration to PF was 55 Gy and 45 days, respectively. Seventy-eight relapses occurred with a 10-year actuarial RFS of 58.2% (standard error +/- 4%). On univariate analysis, increasing PF dose (P = 0.002), age >5 years (P = 0.006), and more thorough extent of surgical resection (P = 0.043) were associated with improved RFS; PFRTD (P = 0.20) and SRTD (P = 0.51) were not associated with RFS. On multivariate analysis, although both PF dose (P = 0.004) and extent of surgery (P = 0.045) remained strongly significant, RT duration was now associated with RFS (P = 0.049). Other factors assessed that did not reach significance were patient age, local tumour extent, presence of internal shunt and use of chemotherapy. The importance of local treatment factors was confirmed in this audit with established prognostic factors such as primary tumour macroscopic resection and adequate PF RT dose being associated with RFS. A treatment time effect is weakly suggested, although less significant than RT dose delivered.

Adolescent↗
PubMed2005

Evaluation of two commercially available, inexpensive alternative assays used for assessing viral load in a cohort of human immunodeficiency virus type 1 subtype C-infected patients from South Africa.

Although human immunodeficiency virus type 1 (HIV-1) RNA is the acknowledged "gold standard" marker for monitoring disease activity in patients receiving highly active antiretroviral therapy (HAART), it remains unaffordable in resource-constrained settings. The present study investigated two commercially available kits for the detection of HIV-1 viral load markers as more affordable alternatives to HIV-1 RNA quantitation. The greatly improved heat-denatured, signal-boosted HiSens HIV-1 p24 Ag Ultra kit (Perkin-Elmer) and the ExaVir Load Quantitative HIV-RT kit (Cavidi Tech AB) were compared with the Amplicor HIV-1 Monitor (version 1.5) assay (Roche Molecular Systems Inc.). A total of 117 samples containing HIV-1 subtype C were analyzed by all three methodologies. Eighty-nine of these samples represented serial measurements from 20 patients receiving HAART. The remaining samples analyzed were from a group of treatment-naive patients. The association between the p24 antigen assay and the RNA assay was fairly strong (R(2) = 0.686). The association between the reverse transcriptase (RT) quantitation assay and the RNA assay was strong (R(2) = 0.810). Both alternative assays seemed most useful for the serial monitoring of patients receiving HAART (n = 89 plasma samples from 20 patients), as all assays showed a statistically significant downward trend over time, with the trend being either linear or curvilinear. In addition, all three assays showed negative correlations with the CD4 count (CD4 count versus RNA load, r = -0.336 and P = 0.001; CD4 count versus p24 antigen level, r = -0.541 and P < 0.0001; CD4 count versus RT level, r = -0.358 and P = 0.0006). Still of major concern are both the lack of sensitivity and the wide degrees of variability of both assays. However, both assays provide a less expensive alternative to the Roche viral load assay and demonstrate the same trends during treatment.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Increase in thyroid follicular cell tumors in nelfinavir-treated rats observed in a 2-year carcinogenicity study is consistent with a rat-specific mechanism of thyroid neoplasia.

The carcinogenic potential of nelfinavir mesylate (nelfinavir) was evaluated in a 2-year oral (gavage) study on Sprague-Dawley rats at dose levels of 0 (control), 0 (vehicle control), 100, 300 and 1000 mg/kg per day. At the end of the treatment, increased incidences of thyroid follicular cell hyperplasia and neoplasms were observed at 300 (males) and 1000 mg/kg per day (both sexes). There were no other treatment-related effects and no tumors at other sites. Results from previous studies indicated a number of effects in the liver and thyroid, as well as metabolic profiles that suggested nelfinavir might cause thyroid hyperplasia/neoplasia secondary to hormone imbalance by altering thyroid hormone disposition. To investigate this hypothesis, the effects of nelfinavir on gene expression in rat hepatocytes and liver slices (in vitro), thyroxine plasma clearance, and thyroid gland function were evaluated. Compared to controls, gene expression analyses demonstrated an increased expression of glucuronyltransferase (UDPGT) and CYP450 3A1 in nelfinavir-treated rat hepatocytes and liver slices. In rats treated with nelfinavir (1000 mg/kg per day) for 4 weeks, liver weights and centrilobular hepatocellular hypertrophy were increased and minimal to mild diffuse thyroid follicular cell hypertrophy and follicular cell hyperplasia were evident in the thyroid gland. Thyroid-stimulating hormone (TSH) levels were significantly increased (three-fold), while tri-iodothyronine (T3)/tetra-iodothyronine (T4) and reverse T3(rT3) levels were unchanged, indicating that a compensated state to maintain homeostasis of T3/T4 had been achieved. Plasma 125I-thyroxine clearance was increased and the plasma thyroxine AUC0-48 was decreased (24%) compared to control. In conclusion, these data indicate that thyroid neoplasms observed in the nelfinavir-treated rats were secondary to thyroid hormone imbalance. Increased thyroxine clearance contributes to the effects of nelfinavir on thyroid gland function and is probably a result of UDPGT induction that leads to elevated TSH levels in the rat and eventual thyroid neoplasia. These results are consistent with a well-recognized rat-specific mechanism for thyroid neoplasms.

Adenocarcinoma, Follicular↗
PubMed2002

Histological tumour response to pre-operative combined modality therapy in locally advanced rectal cancer.

BACKGROUND: Pre-operative combined modality therapy (CMT) is used in locally advanced rectal cancer. Its use affects the clinicopathological staging based on the resected specimen. Assessment of the tumour response in the resected specimen may provide prognostic information. This study was undertaken to determine the histological response to pre-operative chemoradiation and to assess the interobserver reliability of a newly developed tumour response grading system for rectal cancer. METHODS: Pre-operative biopsy specimens and the resected specimens of 21 patients with low rectal cancer were assessed. The patients underwent pre-operative CMT consisting of radiotherapy (45 Gy) with 5-FU either as a continuous infusion or as a bolus intravenous infusion with leucovorin. After four to six weeks tumour response was assessed by comparing pre-operative transrectal ultrasound (TRUS) findings (uT1-4, uN0-1) with postoperative histopathological assessment (pT1-4, pN0-1) using UICC TNM characteristics. Tumour response was defined as a decrease in T status. The histological response to CMT was based on the tumour regression grade (TRG) and ranged from fibrosis extending through the rectal wall with no residual cancer (TRG 1), to no evidence of tumour response (TRG 5). Inter-observer reliability was assessed using weighted and unweighted kappa statistics. RESULTS: Local downstaging was demonstrated in 11/21 (52%) of patients. Three of 21 patients had a TRG 1 response. Thirteen of 21 (62%) patients had TRG 1-3 responses to CMT. There was no significant correlation between local downstaging and TRG. The interobserver correlation coefficient for assessment of TRG was 0.88 (unweighted kappa). CONCLUSIONS: Local downstaging by pre-operative CMT can be demonstrated if pre-operative TRUS staging is compared to standard pathology staging in patients with rectal cancer. Local downstaging is not directly related to histologic response as assessed by TRG. Inter-observer reporting of tumour regression grade (TRG) is reliable.

Journal Article↗
PubMed2002

Tuberculosis in children dying with HIV-related lung disease: clinical-pathological correlations.

SETTING: Chris Hani Baragwanath Hospital, Soweto, South Africa. OBJECTIVES: To compare post mortem histological, microbiological and biochemical findings with clinical and radiological data generated ante mortem in children infected with HIV dying from clinical lung disease. METHODS: Post mortem lung and liver biopsies were undertaken on 93 consecutive deaths in children with HIV. Specimens were processed for culture, histology and staining for M. tuberculosis, Pneumocystis carinii pneumonia (PCP) and cytomegalovirus (CMV). Post mortem diagnoses were compared with clinical and radiological data generated during the final hospitalisation. RESULTS: Tuberculosis (TB) was diagnosed post mortem in four (4.3%) cases; a further 17 (18.2%) patients had been treated empirically for TB before death, and the remaining 72 (77.5%) patients had not been treated for TB. TB was more prevalent in children aged 1 year or older (13.4%) than in younger patients (1.4%) (P < 0.025). Patients with PCP, CMV pneumonitis or lymphocytic interstitial pneumonitis (LIP) had the same clinical presentation or radiographic appearances as patients with TB. The only features distinguishing patients with TB were older age and ante mortem gastric aspirate cultures positive for M. tuberculosis. CONCLUSION: The diagnosis of TB in children infected with HIV remains difficult. Clinical and radiographic features are shared with other opportunistic diseases. Case identification strategies relying on clinical and radiographic findings lead to overtreatment, particularly in children younger than 1 year of age. Gastric aspirate cultures remain a reliable tool for the identification of infected patients.

Age Factors↗
PubMed2001

Extracorporeal irradiation for malignant bone tumors.

PURPOSE: Extracorporeal irradiation (ECI) has been used selectively in the management of primary malignant bone tumors since 1996. We report our techniques for ECI and the short-term oncologic and orthopedic outcomes. METHODS AND MATERIALS: Sixteen patients with primary malignant bone tumors were treated with ECI from 1996 to 2000. The median age was 14 years. The histologic diagnoses were Ewing's sarcoma (11), osteosarcoma (4) and chondrosarcoma (1). The treated sites were femur (7), tibia (4), humerus (2), ilium (2), and sacrum (1). Following induction chemotherapy in Ewing's sarcomas and osteosarcoma, en bloc resection of the tumor and tumor-bearing bone was performed. A single dose of 50 Gy was delivered to the bone extracorporeally using either a linear accelerator (9 cases) or a blood product irradiator (7 cases). The orthopedic outcome was recorded using a standard functional scale. RESULTS: At a median follow-up of 19.5 months, there were no cases of local recurrence or graft failure. One patient required amputation due to chronic osteomyelitis. For the 10 patients with follow-up greater than 18 months, the functional outcomes were graded good to excellent. CONCLUSION: The short-term oncologic and orthopedic results are encouraging and suggest that ECI provides a good alternative for reconstruction in limb conservative surgery in selected patients. This technique should only be used in a multidisciplinary setting, where careful follow-up is available to assess the long-term outcomes.

Adolescent↗
PubMed2001

Induction of interleukin-6 and oncostatin M by radiation in Kaposi's sarcoma cell lines.

PURPOSE: To define the in vitro radiosensitivity of Kaposi's sarcoma (KS) and to explore the mechanism of its extreme clinical radiosensitivity. METHODS AND MATERIALS: The radiation survivals of the three KS cell cultures (KSY-1, KS-JD, KS6-3E) were determined by clonogenic assay and MTT assay. Supernatants from irradiated cells were collected at different time points for measurement of the interleukin 6 (IL-6), oncostatin M (OSM), and basic fibroblast growth factor (bFGF) by ELISA. Changes in the mRNA expression of these cytokines were examined by reverse transcription polymerase chain reaction and Southern blot hybridization. Fresh KS cells were preincubated with the irradiated supernatant before irradiation, and the change in survivals were assessed. RESULTS: The mean SF-2 (survival fraction after 2 Gy) for KS was 0.43. Preincubation with the irradiated supernatant reduced the SF-2 significantly from 0.43 to 0.33 (p < 0.05). Treatment with irradiated supernatant alone was not cytotoxic to the cells. Radiation induced IL-6 and OSM production by KS cells at the transcription level. A single dose of 2 Gy increased IL-6 and OSM mRNA expression of the KS Y-1 cells. This corresponded to an increase in the IL-6 and OSM levels in the culture medium. There was no significant change in the level of bFGF. Preincubation with recombinant human IL-6 or OSM sensitized KS in a dose dependent manner. CONCLUSION: The low SF-2 value for these KS cell lines correlates with the clinical radiosensitivity of KS. The high radiosensitivity may be due to radiation induction of cytokines such as IL-6 and OSM, which are radiosensitizers for KS cells.

Blotting, Southern↗
PubMed2001

In vitro effects of radiation on human retinoblastoma cells.

Retinoblastoma (Rb) is the most common intraocular tumor of childhood and has been demonstrated clinically to be very sensitive to external beam radiation (EBR). The purpose of this study was to determine the survival of Rb cell lines at different endpoints following irradiation. We also studied Rb-reconstituted cell lines postirradiation to gain insight into the role of Rb following DNA damage. Suspension cultures were exposed to single doses of 1, 2, 5, and 10 Gy. Following irradiation, cell viability and cell death was assessed for up to 72 hr using Trypan blue exclusion and acridine orange/ethidium bromide (AO/EB) staining, respectively. Morphological features were examined with light and electron microscopy (LM and EM). Clonogenic survival was assessed 2 weeks postirradiation. Cell cycle distribution was analyzed by flow cytometry. A time- and dose-dependent decrease in cell viability was induced in Y79 and WERI-Rb1 cells following irradiation, although not below approximately 45% for the times and doses used. A similar but much-reduced effect on viability was observed in Rb-reconstituted cells. AO/EB staining, LM, and EM revealed features characteristic of apoptosis following irradiation and a time- and dose-dependent increase in apoptosis was observed. For Y79 and WERI-Rb1 cells, 30-40% apoptosis was observed 72 hr after 10 Gy irradiation; however, apoptosis was much reduced in Rb-reconstituted cells (approximately 8% Y79LxRb28; approximately 18% WERILxRb8). Rb cell lines were extremely sensitive to radiation, although less so in Rb-reconstituted lines, with clonogenic survivals after 2 Gy (SF2) of 0.14 for Y79, 0.06 for WERI-Rb1, 0.36 for Y79LxRb28, and 0.19 for WERILxRb8. Postirradiation, a sub-G1 population was observed, consistent with radiation-induced apoptosis, and Rb-reconstituted cells displayed a prolonged G2 phase. The clonogenic survival parameters of Rb cell lines are consistent with clinical observations, where extreme sensitivity to irradiation has been reported. Additionally, Rb protein protected cells from DNA damage and may also play a role in radiation-induced G2 delay. This in vitro approach provides a useful model for further radiobiological studies of Rb.

Acridine Orange↗
PubMed2001

Extracorporeal irradiation--novel use of a blood product irradiator.

A Cs-137 blood product irradiator (BPI) is used for extracorporeal irradiation of bone grafts. For dose verification purposes two bone phantoms were constructed of plaster of Paris and irradiated in the BPI. The first was a hollow cylinder measuring 15 cm x 3.3 cm to simulate cortical bone, filled with paraffin wax to simulate yellow bone marrow. The second was a concave ellipse 11.5 cm x 9.5 cm x 2.5 cm to simulate a section of ilium. The absorbed dose was measured with radiochromic film in the phantoms and in water for comparison with the manufacturer's calibration certificate. The relative dose distribution in the bone phantoms was measured using Li-F thermoluminescent dosimeters and normalized to a reference point near the centre of each phantom. The doses measured in water matched the calibration certificate within 4%. The doses measured at the cylindrical and elliptical phantom reference points were 49.9 Gy and 52.3 Gy respectively, compared to the nominal dose of 50.0 Gy. The relative doses within the cylindrical phantom ranged from 88% to 100% along the central axis of the wax cylinder, from 89% to 100% along the plaster/wax interface, and from 90% to 103% along the outer surface of the plaster cylinder. The relative doses within the elliptical phantom ranged from 100% to 108% along the inside surface, from 99% to 107% along the outer surface, and from 98% to 103% through the centre of the plaster ellipse. These data agree well with the isodose plot provided by the manufacturer.

Blood↗
PubMed2001

An investigation of underfoot accidents in a MAIM (Merseyside Accident Information Model) database.

Underfoot accidents taken from a study of patient interviews have been analysed to investigate factors that may be implicated in the causes of the accidents. Within the sample of patients in this study women holding items are more at risk than men from underfoot accidents. Carrying items such as shopping and handbags may obstruct the line of sight to underfoot hazards, affect balance and adversely affect reflex corporal movements that may help prevent injury.

Accidental Falls↗
PubMed2001

Palliative radiotherapy of bone metastases: an evaluation of outcome measures.

The objective of this study was to identify and evaluate important patient-based outcomes that are specific to the palliative radiotherapy of bone metastases. We first conducted a literature review to identify and evaluate outcomes that are currently in use. To identify outcomes that are important to patients, in-depth patient interviews were conducted. Finally, issues identified through the interviews were quantified through a prospective survey, in which patients completed a questionnaire prior to commencing radiotherapy and again after 6 weeks. In our literature review, we found that there was no standardized definition of either response to radiotherapy or assessment of pain relief. Pain measurement in many studies was undertaken using very simple measures, which could possibly yield inaccurate results. The vast majority of studies did not include quality of life as an endpoint. The patient interviews and survey showed that chronic pain and associated limitation of movement were the disease symptoms causing the most concern. Having a clear, alert mind and being able in self-care were the aspects of daily living given the highest priority. Sustained pain relief and minimizing the risk of future complications were the main priorities relating to radiotherapy treatment. The practical aspects of treatment (travelling distance, remaining at home and brevity of treatment) were of least importance. This study indicates the complexity of evaluating the outcomes of palliative interventions, and confirms the deficiencies of pain relief as the primary end-point. The patient's quality of life is affected by many factors other than pain (such as limited mobility, reduced performance, side effects and impaired role functioning); hence a wider range of end-points is required. Greater sensitivity is required than in currently used end-points. Concurrent diseases as well as concurrent therapies can make it difficult to attribute effects with precision. Unless such factors are considered in research design, the results may prove unreliable.

Analgesics↗
PubMed2001

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and multiple myeloma in South Africa.

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) has been implicated in the etiopathogenesis of multiple myeloma. Although the association is biologically plausible and attractive, conflicting data have been reported, including evidence against the involvement of KSHV in the pathogenesis of the disease. The purpose of this study was to determine the relationship between KSHV and myeloma in blacks in South Africa, in whom the disease is not uncommon and the seroprevalence of KSHV is higher than in the areas in which this association has been documented. Using a nested polymerase chain reaction (PCR) assay, the authors initially tested for the presence of KSHV DNA sequences (KS330(233)) in bone marrow aspirates, bone marrow biopsy material, and cultured bone marrow adherent cell samples of patients with myeloma. KSHV DNA sequences were detected in 4 of 10 (40%) of the adherent cell cultures and 1 of 20 (5%) of the bone marrow aspirate samples. None of the bone marrow biopsy samples (0/9) or control bone marrow aspirate samples (0/19) was positive. To confirm the positive results in the bone marrow cultures noted above and to exclude contamination, the procedure was repeated in a further 7 patients with myeloma and 11 controls with lymphoproliferative disorders using the same nested PCR assay. In addition, the authors used a different set of primers that recognize sequences internal to the 233-bp fragment to yield a final product of 186 bp. The authors were unable to detect any KSHV DNA sequences in the patients with myeloma (0/7) or the control patients with other lymphoproliferative disorders (0/11). Taken together, the finding of a positive result in 4 of 17 patients (23.5%), which is similar to the background seroprevalence rate, does not support a clear association between myeloma and KSHV in blacks in South Africa.

Adult↗
PubMed2000

Locally advanced melanoma: results of postoperative hypofractionated radiation therapy.

BACKGROUND: High rates of locoregional recurrence have been reported from surgical series of locally advanced melanoma. In this study, the outcomes of patients treated with surgery and postoperative hypofractionated radiation therapy were reviewed to assess local recurrence and survival. METHODS: From 1989 to 1998, 174 patients with International Union Against Cancer Stage I-III melanoma received postoperative radiation therapy, either as a component of their initial management or following surgery for recurrence. Radiation was delivered to the primary site in 35 cases and involved regional lymph nodes in 139. The indications for irradiation included microscopically positive surgical margins or other adverse pathologic features. All patients received a hypofractionated schedule of 30-36 grays (Gy) in 5-7 fractions over 2.5 weeks. RESULTS: Recurrence within the radiation fields was identified in 20 patients (11%) at a median time of 6 months. There was no difference in recurrence rates for patients with microscopically positive margins compared with other indications for adjuvant treatment. The main complication of treatment was symptomatic arm lymphedema in 58% of patients following axillary dissection and postoperative irradiation. The median disease specific survival for the entire group was 25 months from radiation therapy, and the 5-year survival was 41%. The only factor that predicted significantly for decreased survival was infield recurrence (the median survival periods were 13 months and 35 months for those with and without infield recurrence, P < 0.0001). The median time to the development of distant metastasis was 19 months. CONCLUSIONS: Despite the high incidence of distant metastasis, locoregional control remains an important goal in the management of melanoma. Compared with published surgical data, postoperative adjuvant radiation therapy given according to a hypofractionated schedule was effective in reducing local recurrence in patients at high risk of locoregional failure.

Adolescent↗