Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study

Few data are available to help predict which older cancer patient is at risk of developing chemotherapy-related toxicity. This study was a pilot for a project designing a predictive risk score. Chemotherapy patients aged 70 years and older were prospectively enrolled. Chemotherapies were adjusted for their published toxicity. 60 patients were enrolled, 59 were evaluable. Mean dose-intensity was 90.3%, range 33.3-129.0%. 47% of the patients experienced grade 4 haematological and/or grade 3-4 non-haematological toxicity. Published toxicity (MAX2), diastolic blood pressure, marrow invasion and lactate dehydrogenase (LDH) were all associated with toxicity (P<0.1); Body Mass Index, previous chemotherapy, red blood cells, platelets, polymedication with dose-intensity; and polymedication with FACT-G change. After adjustment for the published toxicity, the variables retained their significance, except for LDH and polymedication (for dose-intensity). Although the size of this pilot study imposes a cautious interpretation, patient-related and chemotherapy-related variables correlated independently with toxicity. Designing a composite predictive score to use in assessing the toxicity of multiple chemotherapy regimens therefore appears to be a valid undertaking.     

The prospectively observed course of illness among depressed patients who commit suicide

OBJECTIVE: These analyses were conducted to describe the course of illness among patients with major affective disorders who commit suicide. METHOD: Twenty-nine patients who entered a long-term, high-intensity follow-up study of major affective disorders and who later committed suicide within 1 year of their last follow-up interview were individually matched to other patients by age, sex, the presence or absence of lifetime drug or alcohol abuse, time to last interview and polarity. Those who suicided were compared with their controls by depressive and substance abuse morbidity during follow-up, treatment resistance, treatment compliance, suicidal behavior and psychosocial adjustment. RESULTS: Among the various measures used to characterize the course of illness during a mean follow-up of 4.3 years, only those pertaining to suicidal behavior robustly separated the suicide group from their controls. Suicidal behavior in the remote past seemed as predictively important as suicidal behavior during follow-up. CONCLUSION: Of the various features monitored over time in patients with major affective disorder, suicidal behavior itself was the clearest correlate of risk for completed suicide.     

Self-image as a Predictor of Outcome in Adolescent Major Depressive Disorder

Abstract— We investigated the ability of a measure of self-image, two measures of depression, and demographic characteristics to predict the outcome of depressive symptoms. Subjects were 47 adolescents who were referred to outpatient treatment for depression. Subjects were assessed for depressive symptoms at three time periods. Self-image as measured by the Offer Self-image Questionnaire (OSIQ) was a significant predictor of depressive symptoms at both 3 months and 1 year. That was independent of initial levels of depression. The two most predictive scales from the OSIQ, were the emotional tone and mastery of the external world scales. The results are consistent with previous research indicating the importance of self-image in adolescent depression The implications of these findings for treatment of adolescent depression are discussed.     

Enhancing the immunotherapeutic potential of mycobacteria by transfection with tumour necrosis factor-alpha

In an attempt to enhance the anti-tumour properties of mycobacteria we have developed recombinant forms of Mycobacterium smegmatis which express and secrete biologically active human tumour necrosis factor-alpha (TNF-alpha). This was achieved by transfecting M. smegmatis using shuttle plasmids incorporating the cDNA sequence for the human TNF-alpha mature peptide. In vitro experiments on a panel of human bladder tumour cell lines (EJ18, MGH-U1, RT4, RT112) indicate that our genetically modified mycobacteria are more effective than wild-type at inducing or up-regulating the expression of intracellular adhesion molecule-1 and the secretion of an array of proinflammatory cytokines [interleukin-1 (IL-1), IL-6, IL-8, granulocyte-macrophage colony-stimulating factor]. We have also demonstrated increased adhesion molecule and cytokine expression in response to mycobacteria transfected with vector containing no gene insert. However, this was not as pronounced as that observed following tumour cell stimulation by the TNF-alpha-transfected strain. In contrast, in three out of four tumour cell lines all M. smegmatis strains were found to down-regulate the secretion of the anti-inflammatory cytokine transforming growth factor-beta1. Our studies have also confirmed that M. smegmatis is a powerful inhibitor of bladder tumour cell growth and revealed that its antiproliferative potency is enhanced by transfecting with human TNF-alpha and, to a lesser extent, with vector alone. All M. smegmatis strains were effective in the activation of peripheral blood leucocyte cultures. However, no differences were observed in the ability of the TNF-alpha-transfected, mock-transfected and wild-type mycobacteria to induce tumour cell killing activity. These results suggest that the immunomodulatory effects of M. smegmatis can be enhanced by transfection with vectors which allow the secretion of human TNF-alpha, thus increasing mycobacterial immunotherapeutic potential.     

Prevalence in a volunteer population of pelvic cancer detected with transvaginal ultrasound and color flow Doppler.

Our objective was to find the prevalence of non-symptomatic endometrial and ovarian neoplasms in a volunteer population of women, aged 40 and over. We offered a free volunteer screening program to asymptomatic women for a study using transvaginal ultrasound and color flow Doppler for the detection of pelvic cancer. In the first 2 years, 2117 women were examined, 51.3% post-menopausal. An ovarian cyst was defined as having a maximum diameter of more than 2.4 cm. Color flow was used to identify blood vessels feeding pelvic organs and adnexal enlargements. An abnormal Doppler flow velocity for the ovary was defined as a resistance index of less than 0.41. Ovarian cysts of less than 5 cm with normal Doppler indices were followed up in 6 months to 1 year. An adnexal morphology score was created to quantify the usefulness of this parameter, particularly in postmenopausal women. Indications for surgery were pre-defined as a persistent ovarian cyst of more than 5 cm, a persistent suspicious Doppler and a total endometrial thickness of greater than 0.59 cm in postmenopausal women not taking hormones.A total of 202 women (9.5%) had ovarian cysts. Fourteen women were operated upon because of size criteria, one because of family history and three for persistent abnormal flow. By Doppler study, 15 cysts were predicted to be benign and histology was confirmatory. There were two false positives and one true positive, a stage Ib ovarian cancer. There were no false negatives, although a stage I endometrioid cancer of the ovary was detected 8 months after a negative scan. In those cases in which follow-up data were available, 56% of the cysts regressed in premenopausal women. In postmenopausal women, 28% regressed. Twenty of 1086 postmenopausal women had endometrial biopsies. Three had endometrial cancer, two stage I and one stage IIA. Five had atypical or adenomatous hyperplasia, and seven had benign polyps.So many women have small asymptomatic cysts of the ovary that a major reorientation of physicians' attitudes towards the ovary will have to be introduced to adapt to this new information. In this population, the prevalence of benign epithelial ovarian neoplasms was 7/1000, and of malignancy was 05/1000. In postmenopausal women, the prevalence rate for endometrial cancer was 5/1000, with 5/1000 hyperplasias and 7/1000 benign polyps. When endometrial and ovarian cancer screening are combined, the yield is comparable to that seen in breast and cervical cancer screening.     

Human poisoning with pentachlorophenol and its treatment

A case of intentional intoxication with pentachlorophenol has been described. Salient features observed included pyrexia, diaphoresis, hyperkinesis, muscle twitching, tremors, epigastric tenderness, leg pain, tachypnea, and tachycardia. The patient's restlessness and agitation were controlled with phenytoin and phenobarbital. Forced diuresis with furosemide and mannitol resulted in a large increase in urinary excretion of pentachlorophenol. It is suggested that such therapy may be life saving in such intoxications.