Thio TEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80

Summary A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thio TEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. Thio TEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thio TEPA absorbed, ranging from 20%–78%. Peak plasma levels of thio TEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thio TEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thio TEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 g h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thio TEPA alone, the dose should be reduced with Tween 80.     

Neuropsychologic status in multiple sclerosis after treatment with glatiramer

BACKGROUND: Glatiramer acetate (Copaxone) therapy reduces clinical disease activity in relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To study the effect of glatiramer therapy on neuropsychologic function as part of a randomized, placebo-controlled, multicenter trial. METHODS: Two hundred forty-eight patients with relapsing-remitting MS and mild to moderate disability (Expanded Disability Status Scale score, <5.0) were tested before and 12 and 24 months after randomization to administration of glatiramer acetate, 20 mg/d, or matching placebo. Neuropsychologic tests examined 5 cognitive domains most often disrupted in patients with MS: sustained attention, perceptual processing, verbal and visuospatial memory, and semantic retrieval. RESULTS: Baseline neuropsychologic test performance was similar in both treatment groups and was within normal range, except for impaired semantic retrieval. Mean neuropsychologic test scores were higher at 12 and 24 months than at baseline, and no differences were detected between treatment groups over time. No significant interactions were detected between treatment and either time or baseline impairment. CONCLUSIONS: Our 2-year longitudinal study showed no effect of glatiramer therapy on cognitive function in relapsing-remitting MS. Although it is possible that glatiramer therapy has no effect on cognitive function, the lack of measurable decline in cognitive function in both patient groups for 2 years limits the opportunity for glatiramer to demonstrate a therapeutic effect by minimizing such decline. Emerging treatments for MS should continue to be examined for their effect on cognitive impairment because it can be a critical determinant of disability. A greater understanding of the natural history of cognitive decline in MS is essential for a rational design of these drug trials.     

The economic impact of foot and mouth disease and its control in South-East Asia: a preliminary assessment with special reference to Thailand.

A pilot study of the economic impact of foot and mouth disease (FMD) in the countries and region of South-East Asia is described. Previous economic impact assessments are reviewed and summarised and a synthesis of these contributions is constructed. A framework for the future economic impact of the disease is then developed, incorporating analyses at the sectoral (production system), national and regional levels. Data requirements for such studies are also identified. Integrated epidemiological and economic models for impact assessment were developed and applied to the case study country of Thailand. The models were used to evaluate the economic viability of FMD control programmes in the country. Scenarios evaluated include the effect of improving vaccination coverage and thus reducing productivity losses, and the effect of eventual eradication of the disease. The results indicate that economic returns to the high expenditures incurred in FMD control could be achieved in the short term if greater international trade in pork products was made possible and export prices higher than those in the domestic market could be attained. If FMD were to be eradicated from Thailand in 2010, the eradication would be economically viable, even without exports, with a predicted benefit-cost ratio of 3.73. With additional exports, the economic justification for control becomes much stronger with a benefit-cost ratio of up to 15:1 being achieved. If eradication is not achieved until 2020, returns remain positive without exports, but at a lower rate. The authors propose that the integrated epidemiological and economic models developed be applied to other countries of the region to gain a more accurate insight into the future benefits of FMD control and eradication in the region.     

The influence of host factors and immunogenetics on lymphocyte responses to Hepagene vaccination

We have shown that both demographic and immunogenetic factors are involved in the immune responses of Hepagene vaccinated individuals who were persistent nonresponders to 'S' containing hepatitis B vaccines. The HLA-DRB1 0701; DQB1 0202 genotype was found to be associated with a decline of anti-HBs antibodies (anti-HBs) and were frequent in those individuals who remained nonresponders following booster vaccination. Contrary to previously published 'S' vaccination data, Hepagene stimulated T-cell responses showed a lack of correlation with the humoral responses. Limiting dilution analysis demonstrated that the cellular immune response is associated with the kinetics of exposure to Hepagene rather than magnitude of the anti-HBs response. It remains that despite the inclusion of the pre-S proteins 74% nonresponder vaccinated individuals failed to produce > 100 IU/l of anti-HBs. However, these were persistent nonresponders and it was therefore encouraging that two doses of Hepagene did seroconvert (> 10 IU/L) 61% of this difficult group.     

Intraoperative radiation therapy for carcinoma of the gallbladder

The recognition of a high incidence of local failure following surgical management of adenocarcinoma of the gallbladder has led to the use of adjuvant radiation therapy. In order to deliver higher doses to the gallbladder bed, intraoperative radiation therapy (IORT) has been used both with and without external beam radiation.The experience to date is reviewed. Ten patients have been treated, all of whom had either gross residual or unresected disease. The median survival for the group was approximately 1 year. There were no long-term survivors. The IORT did not contribute to the overall morbidity.Because of the limited number of patients and the advanced nature of the disease, the role of IORT in the management of gallbladder carcinoma has yet to be determined. The utility of this modality will most likely reside in the treatment of minimal residual disease at the time of cholecystectomy rather than in the palliative treatment of unresectable tumors.

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Resumen El reconocimiento de la elevada tasa de falla local en el tratamiento del adenocarcinoma de la vesícula biliar, ha motivado el uso de radioterapia adyuvante. Con el objeto de administrar altas dosis de irradiación al lecho de la vesícula billiar, se ha utilizado la radioterapia intraoperatoria (RTIO) con y sin irradiación externa.Se revisa la experiencia hasta la fecha. Diez pacientes han sido tratados, todos con enfermedad macroscópica residual o no resecable. La sobrevida media para el grupo fue de aproximadamente un año; no hay sobrevivientes a largo plazo. La RTIO no contribuyó a la morbilidad global.Debido al limitado número de pacientes y a lo avanzado de la enfermedad, el rol de la RTIO está aun por determinar. La utilidad de esta modalidad muy posiblemente habrá de residir en el tratamiento de enfermedad residual miima en el momento de la colecistectomiá, más qu en el tratamiento paliativo de tumores no resecables.

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Résumé Reconnaître la fréquence importante des échecs locaux à la suite du traitement chirurgical de l'adénocarcinome de la vésicule a amené à ajouter la radiothérapie. Pour pouvoir donner des doses plus importantes au lit de la vésicule, l'irradiation peropératoire (IP) a été administrée à la fois avec et sans irradiation externe. L'expérience à ce jour a été passée en revue. Dix patients ont été traités qui avaient soit une grosse tumeur résiduelle soit un cancer non réséqué. La survie moyenne du groupe était d'un an à peu près. Il n'y a eu aucun survivant à long terme. L'IP n'a rien changé à la mortalité globale. Compte tenu du nombre limité des patients et de la nature avancée de la maladie, le rôle de l'IP dans le traitement du cancer de la vésicule reste à déterminer. La valeur de l'IP sera probablement de traiter la petite tumeur résiduelle au moment de la cholécystectomie plutôt que les tumeurs non résécables.

     

The longitudinal relationship of hemoglobin, fatigue and quality of life in anemic cancer patients: results from five randomized clinical trials.

BACKGROUND: Anemia is common in cancer and has been associated with fatigue and reduced health-related quality of life (HRQOL). We report the association between hemoglobin and fatigue and the impact of reducing fatigue on several domains of HRQOL. PATIENTS AND METHODS: These analyses were based on five randomized trials. Patients completed the Functional Assessment of Cancer Therapy (FACT) Anemia scales and numeric rating scales of Energy, Activity and Overall Health at baseline and after the 12-week treatment period. t-tests and linear regression models were used to evaluate associations. Analyses were stratified into three groups: solid tumor chemotherapy patients, lymphoproliferative malignancy chemotherapy patients and non-chemotherapy patients. RESULTS: Adjusted mean differences (95% CI) in FACT Fatigue change scores between hemoglobin responders (> or =2 g/dl increase) and non-responders were 3.0 (1.2, 4.7), 2.8 (0.6, 5.0) and 5.8 (2.2, 9.5) among the solid tumor, lymphoproliferative malignancy and non-chemotherapy groups, respectively. Significantly greater improvements (P <0.01) were observed in the FACT well-being scales for patients with meaningful improvement in fatigue (FACT Fatigue change score > or =3 points). After controlling for other factors, patients whose fatigue improved reported substantially greater improvements in energy, ability to perform usual activities and overall health (P <0.0001). CONCLUSIONS: Across five trials of cancer patients on and off chemotherapy, hemoglobin response was associated with meaningful improvements in fatigue, which, in turn, was associated with improved physical, functional, emotional and overall well-being.     

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.