Chemotherapy in stage IV (metastatic) non-small-cell lung cancer. Provincial Lung Disease Site Group

After sciatic transection a strong decrease in immunoreactivity occurred, starting at 2 days. After 6, 10, 14, and 20 days survival only 5% of the sciatic motoneurons were strongly labeled for GluR2/3 against 80% in the control situation. From Day 20, GluR2/3 labeling started to increase again, reaching near normal levels at Day 80 after sciatic transection. In contrast, after sciatic crush, the decrease in GluR2/3 labeling in motoneurons was less pronounced and returned to normal in 30 days. In all animals, the GluR1 and GluR4 labeling of motoneurons remained unchanged after sciatic transection or crush. It is concluded that sciatic nerve injury leads to a strong, time-dependent decrease in the expression of GluR2 and 3 subunits in the corresponding motoneurons. As a consequence, AMPA receptors with a different subunit composition may be assembled, leading to a change in the functional properties of these receptors. Moreover, if they lack the GluR2 subunit, they may become calcium permeable.     

Neuroimaging in children with congenital disorders of the peripheral visual system

The study investigates the neurological substrate in children with congenital disorders of the peripheral visual system (CDPVS), i.e. disorders of the anterior visual pathways and the globe. The design is retrospective; brain MRI and/or CT scans were traced and reviewed for 79 of 254 children with CDPVS on our database. The neuroradiological findings were considered in the context of degree of visual impairment (profound [PVI] and severe [SVI]), developmental outcome (setback and non-setback), and mode of imaging (MRI and CT). Scans were abnormal in 40 of 79 (51%) children; 23 of 40 (58%) had more than one lesion; and in some children lesions not previously reported were found. The number of abnormalities per child was significantly higher in the PVI than the SVI group (P<0.05); the level of significance varied according to the method of scanning (MRI, P<0.001; CT, ns). Seven children were known to have had developmental setback; significantly more brain abnormalities per child were found in the group with setbacks than in the group without (P<0.001). Eighty-six percent (24 of 28) of MRI compared with 38% (22 of 58) of CT scans were abnormal. MRI detected more lesions per child than CT (P< 0.001). Thus, a significant amount of brain pathology occurs in children with CDPVS. The number of lesions varies directly with degree of visual impairment and both correlate with developmental outcome. As brain pathology will be only one of many factors influencing developmental progress in visually impaired children, prospective multifactorial studies of the CDPVS population, which include MRI studies of the neurological substrate, will be required to clarify the latter.     

Management of hormone refractory prostate cancer: current standards and future prospects

PURPOSE: Recent advances in the biology and treatment of hormone refractory prostate cancer are reviewed. MATERIALS AND METHODS: A MEDLINE literature search of secondary hormonal therapy and chemotherapy for hormone refractory prostate cancer was performed. Recent advances in the biology of hormone refractory prostate cancer, changes in the measurement of response to therapy, and testing of new drugs and combinations of drugs were reviewed. RESULTS: Historically the treatment of hormone refractory prostate cancer has been disappointing. Useful parameters to monitor clinical response have been lacking but perhaps more importantly a scarcity of apparently active drugs has contributed to these results. Recently several developments have improved the outlook for treatment of hormone refractory prostate cancer. Recognition of antiandrogen withdrawal responses has had important ramifications for clinical trial interpretation and patient care. Secondary hormonal therapies, such as alternative antiandrogens and anti-adrenal agents, are well tolerated and can provide significant clinical benefits. Combining prostate specific antigen values with quality of life and measurable disease responses has made clinical trial end points more objective and more clinically relevant for the patient. Furthermore, a better understanding of the biology of hormone refractory prostate cancer, refinements in measuring response to treatment and availability of agents with proved palliative capabilities and/or generating greater than 50% response have all lead to improvements in treatment management. In 2 randomized studies mitoxantrone in combination with steroids has demonstrated significant palliative benefit compared with steroids alone. In phase II studies more than half of patients respond to estramustine combinations with vinblastine, etoposide or paclitaxel. Other novel combinations and new drugs currently are being tested. CONCLUSIONS: Recent advances suggest that available therapies for hormone refractory prostate cancer can have a meaningful impact on the disease. Improving treatment of hormone refractory prostate cancer remains an area of active investigation.     

The development and psychometric validation of a brain cancer quality-of-life questionnaire for use in combination with general cancer-specific questionnaires

A self-report questionnaire module consisting of 24 items, comprising 5 scales and 7 single items, has been developed for measuring health-related quality of life in patients with brain cancer. Module development proceeded through several stages, including a listing of patient, family and health care professional concerns, the writing of items, field testing in 105 patients with brain cancer and subsequent item reduction and scale construction after multitrait scaling analysis and assessment of internal consistency (Cronbach's coefficient alpha). The final version of the module exhibits reasonable test-retest stability over a period of one week. Differences in the responses between patients with recently-diagnosed and recurrent cancer and between patients with a Karnofsky Performance Score (KPS) of 50-70 and 80-100 were in the expected direction, indicating that the module of questions is responsive to differing conditions. Patients with either mental confusion, motor deficit or dysphasia indicated problems in several domains and single items as compared to patients without these neurological deficits. Thus, differences in the responses to the items in the brain cancer module appear to reflect differences in neurological status. In addition, deteriorating neurological status was accompanied by a marked increase in emotional distress, future uncertainty and motor dysfunction. A comparison of the responses in the module with the KPS and with a modified Barthel Activities of Daily Living Index (BADLI) shows moderate correlations, primarily with scales and items that pertain to motor dysfunction, while other scales (such as emotional distress, visual disorder and communication deficit) and most single items are not associated with the KPS or BADLI. Since the emotional distress scale of the module was found to be highly correlated with the emotional function scale of the EORTC QLQ-C30, it could be omitted when the module is used in combination with the QLQ-C30. This would reduce the module to a total of 20 items with four scales and seven single items. The intention is to combine this module of questions with other core or general quality-of-life questionnaires when studying patients with brain cancer in clinical trials.     

Cardio-ventilatory control in rainbow trout: II. Reflex effects of exogenous neurochemicals

The effects of various neurochemicals were examined in intact, unanesthetized rainbow trout (Oncorhynchus mykiss) to assess the role of branchial O2-sensitive chemoreceptors in the cardio-ventilatory responses to exogenous neurochemicals. cyanide stimulated ventilation and elicited bradycardia when give externally but only stimulated ventilation when injected internally. Norepinephrine increased heart rate, blood pressure and ventilatory rate but opercular pressure was not affect. Dopamine had no effect on either heart or ventilatory rate but increased blood pressure and decreased opercular pressure. Serotonin stimulated heart rate and ventilation but decreased blood pressure. Acetylcholine and nicotine stimulated all cardio-ventilatory variables. Muscarine decreased heart rate and blood pressure and had a biphasic effect on ventilation. These results, combined with the results from the preceding study, suggest that the cardio-ventilatory effects of exogenously administered (1) cyanide are entirely mediated by gill O2 receptors, (2) serotonin, and cholinergic drugs could be partly mediated by O2 receptors and (3) catecholaminergic drugs are not mediated by O2 receptors.