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Biomedical subjects

D Guerrero

Publications and source records attributed to D Guerrero.

At least 19 recordsLinked to original sources

Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration.

PURPOSE: To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. PATIENTS AND METHODS: Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19-77). RESULTS: Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. CONCLUSION: Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.

Adult

Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVE: To assess the role of Fas-mediated apoptosis in the salivary glands of patients with primary Sjögren's syndrome (SS). METHODS: Expression of Fas, Fas ligand (FasL), and bcl-2 in salivary gland biopsy material was detected in situ by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. DNA fragmentation in apoptotic cells was assessed by the enzymatic incorporation of labeled nucleotides (digoxigenin-dUTP). RESULTS: The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis. The majority of infiltrating lymphocytes in SS were Fas+ and bcl-2+, while few lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell death of lymphocytes, particularly in dense periductal foci. Lymphocytic cell death was significantly lower (P < 0.0001) in these foci compared with that in the interstitium. CONCLUSION: Infiltrating lymphocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though they may express Fas. The presence of bcl-2 in these cells may explain their inability to undergo apoptosis. The acinar epithelial cells, in contrast, may undergo Fas-mediated apoptosis. These results suggest that the Fas death pathway may be an important mechanism leading to the glandular destruction found in SS.

Apoptosis

Verbally administered Barthel Index as functional assessment in brain tumour patients.

OBJECTIVE: To investigate verbally administered Barthel Index as a measure of functional status in patients with high grade gliomas. BACKGROUND: Barthel Index (BI) is a performance score of activities of daily living which has been validated in patients with neurological disability. While any assessment of quality of life in brain tumour patients should include all the aspects of CNS function we concentrated on measurement of physical performance status and evaluated the role of BI as a measure of palliative effect of treatment in patients with high grade glioma undergoing radiotherapy. METHODS: BI was verbally administered on 504 occasions in 107 patients with high grade glioma. The BI scores were correlated with Karnofsky performance score (KPS), and neurological performance score (NPS) as a measure of inter-index reliability. The BI's prognostic value was assessed using actuarial survival data. RESULTS: BI was sensitive to change and reflected the degree of functional impairment. In patients with high grade glioma BI correlated with KPS, and NPS (R2 = 0.872 and 0.658 respectively). BI score was also of prognostic value in terms of survival. The median survival of patients with functional independence was 9 months with moderate disability 5 months and with severe disability 4 months. CONCLUSION: Verbally administered Barthel Index is easy to use, reliable and sensitive to change and is of prognostic value. It is a useful tool in the management of patients with gliomas, as an objective evaluation of palliative effectiveness of treatment in patients with functional disability.

Activities of Daily Living

Correlative transmission electron microscopy examination of nondemineralized and demineralized resin-dentin interfaces formed by two dentin adhesive systems.

The resin-dentin interface formed by two dentin adhesives, Optibond (OPTI, Kerr) and Scotchbond Multi-Purpose (SBMP, 3M), was ultramorphologically examined by transmission electron microscopy (TEM). Ultrastructural information from nondemineralized and demineralized sections was correlated. It was hypothesized that the different chemical formulations of the two adhesives would result in a different morphological appearance of the hybrid layer. Ultrastructural TEM examination proved that each of the two dentin adhesive systems was able to establish a micromechanical bond between dentin and resin with the formation of a hybrid layer. However, the interfacial hybridization process that took place to produce this resin-dentin bond appeared to be specifically related to the chemical composition and application modes of both systems. OPTI consistently presented with a hybrid layer with a relatively uniform ultrastructure, electron density, and acid resistance. These three parameters were found to be more variable for the hybrid layer formed by SBMP. Characteristic of SBMP was the identification of an amorphous phase deposited at the outer surface of the hybrid layer. Although both adhesive systems investigated follow a total-etch concept, their specific chemical formulations result in different interfacial ultrastructures that are probably related to different underlying bonding mechanisms. The clinical significance of these morphological findings, however, is still unknown.

Acid Etching, Dental

Modifying the Barthel Performance Index Score for use in patients with brain tumours.

Performance status scores are useful tools in the management of patients with malignant disease. No specific performance index score exist, however, for patients with glioma. The Barthel Index, has been used in our department because it has been widely used in patients following stroke and found useful. This study aims to establish whether a modification of the Barthel Index would be more appropriate for patients with glioma and, if so, what modifications should be made. The opinions of multidisciplinary health workers and carers experienced in helping patients with glioma were established by questionnaire. Difficulty with speech and the presence of seizures were statistically ranked the most significant disability in terms of overall performance status. As these are not included in the Barthel Index a modification is justified. However, to include new categories in a performance index but avoid increasing its complexity, existing categories have to be omitted. Therefore, the second aim of this study was to establish which categories within the Barthel contribute least to a change in the total score. Three-hundred-and-thirty-three prospectively recorded Barthel scores were evaluated in 81 patients over 2 years and the individual categories evaluated by multifactor analysis. The sensitivity of the categories 'bowel function' and 'independence in grooming' to a change in the total score was less than 1%. In conclusion, substituting 'speech difficulties' and the presence of seizure in place of 'bowel function' and 'independence in grooming' from the Barthel Index will improve the specificity for patients with glioma without reducing the sensitivity or acceptability for the patients and research nurses who most often complete them.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

Pulmonary arteriovenous fistula ruptured to pleural cavity in pregnancy.

Congenital pulmonary arteriovenous fistula is frequently associated with hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease). With the increased blood flow in pregnancy such fistulas enlarge, occasionally giving rise to haemothorax, which generally has a poor prognosis. A familial case is presented in which massive haemothorax required emergency thoracotomy in the 27th week of pregnancy.

Adult

Use of antithrombin III in critical patients.

OBJECTIVE: To evaluate the effect of the AT III concentrates upon the clinical evolution and hemostatic parameters. DESIGN: Prospective, open, randomized trial. PATIENTS AND PARTICIPANTS: Septic and multiple trauma patients admitted to our Intensive Care Unit. SETTING: Levels of AT III below 70% were used as criteria to choose 36 patients, 20 of whom received treatment with AT III and 16 did not. INTERVENTIONS: AT III concentrates were administered at an initial dose of 60 U/kg followed by 10 U/kg every six hours. RESULTS: The administration of AT III neither contributes to alterations in haemostasis, nor the clinical evolution (evaluated according to Apache II score). CONCLUSIONS: The results suggest that the administration of AT III concentrates to critical patients with acquired low levels, but without manifest DIC, may not be justified; although further studies on a larger population are required to establish definite conclusions.

APACHE

Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma.

We report the palliative effectiveness of a hypofractionated radiotherapy regimen in patients with poor prognosis high grade glioma. Thirty-eight elderly, and/or disabled patients received radiotherapy to a dose of 30 Gy in 6 fractions over 2 weeks to a planning target volume defined by the enhancing tumour and a 2-cm margin. The median survival was 6 months with a 1-year survival rate of 23%. Treatment was without acute toxicity. One month after radiotherapy, functional status, assessed using a verbally administered Barthel index, improved in 38% and remained stable in a further 39% of surviving patients. At 3 months 39% of surviving patients had improved and a further 12% remained stable. We conclude that in the poor prognostic group of patients with high grade glioma hypofractionated partial brain radiotherapy is well tolerated, convenient and provides effective palliation in a proportion of patients. Comparison with conventional radiotherapy or symptomatic care alone require further evaluation in randomised studies.

Activities of Daily Living

Who should follow up cancer patients? Nurse specialist based outpatient care and the introduction of a phone clinic system.

The objective of this study was to pilot and evaluate a nurse based follow-up system for oncology patients in terms of feasibility and impact on outpatient oncology practice. We identified clinical situations with a defined range of clinical problems, which were set out on a proforma (Appendix) for a nurse consultation. Following a period of training, surveillance during radiotherapy was transferred to a nurse 'on treatment clinic' and a defined point of post-treatment follow-up to a nurse 'phone clinic'. The effectiveness of the nurse based follow-up was assessed by a prospective analysis of the consultation records. The impact on clinical practice was assessed in the form of audit of the clinic work-load before and after introduction of the nurse follow-up service. The patient assessment by the nurse specialist was satisfactory and covered the range of problems encountered. Medical referral by the nurse specialist was necessary in 3/33 on treatment assessments and 1/61 phone appointments. The medical outpatient work-load was estimated to decrease by 30%. Structured follow-up by a skilled and trained nurse specialist provides excellent support and effective medical surveillance in defined situations in oncology follow-up. Patients appeared satisfied with the arrangement and the pilot study suggested up to 30% reduction in the medical outpatient work-load. The use of 'phone clinics' offers an effective alternative to the conventional outpatient clinic model, while being less costly and more convenient for patients and staff.

Ambulatory Care Facilities

Gaps in cardiovascular medication taking: the tip of the iceberg.

OBJECTIVE: To search for major gaps in medication-taking behavior predisposing patients to cardiovascular morbidity and mortality. DESIGN: Convenience sample; cohort prospectively followed for < or = 5 months. SETTING: General internal medicine and cardiology clinics in a university medical center. PATIENTS: From among 893 patients, the authors identified 132 eligible individuals and entered 33 subjects (25%) with chronic cardiovascular conditions, 1-3 chronic oral medications for these conditions, overall regimen of < or = 6 drugs, regular visits at 1-3-month intervals, literacy in English, willingness to use electronic monitors, and physician permission to participate. OUTCOME MEASURES: Medication compliance rates and patterns by patient self-report, physician estimates, pill count, and electronic monitoring of pill vial opening. RESULTS: Despite moderately complex regimens (5.4 +/- 0.5 pills daily; range 1-11), most subjects took most medications according to the prescription: median intervals between pill vial openings were 1.00, 0.50, and 0.43 days for once, twice, and three times daily dosing, respectively. Medication-taking gaps of > or = 2 times the prescribed interdosing interval occurred for 48% of the patients. Patients' dosing patterns often produced "uncovered" intervals (mean duration 3.7 days, range 0-25) with doubtful pharmacologic effectiveness. These lapses were underestimated by patients and poorly perceived by their treating physicians, despite familiarity with their care. Baseline sociodemographic, psychosocial, medical system, or clinical characteristics did not predict the patterns or degrees of medication noncompliance. CONCLUSIONS: Major treatment gaps occur frequently, even in carefully selected ambulatory populations, and generally escape detection. The compliance patterns and gaps may contribute to reported excesses of cardiovascular morbidity and mortality.

Adult