Cell survival characteristics of a human colon adenocarcinoma cell line after photodynamic treatment: a comparison of Photofrin II and TPPS

A comparison has been made of the in vitro light-activated drug cytotoxicities of two different porphyrin compounds, Photofrin II and TPPS4. An early passage human colon adenocarcinoma cell line, WiDr, has been exposed to either drug for 24 h, the excess drug washed from the cells and the cells irradiated with light using quartz-tungsten-halogen lamps. Neither light nor drug alone under the experimental conditions employed was toxic to WiDr cells. Together, considerable cytotoxicity could be seen and the shapes of the cell survival curves following exposure to either drug then irradiation with light, were similar. For equal amounts of drug in the medium, Photofrin II was a more efficient photosensitizer of WiDr cells than TPPS4, and differences in cellular uptake could only partly explain this. When the experimental procedure was changed by reducing the temperature of irradiation, a reduction in photosensitizing efficiency could be demonstrated. This was more pronounced for Photofrin II, and was seen as a change in the slope of the final portion of the survival curve; and as a change in the shoulder for TPPS4. Two different batches of the two drugs were compared and shown to give slightly different results for Photofrin II (change in shoulder) but not to differ for TPPS4.     

Noncortical origins of the spinal motor evoked potential in rats

Motor evoked potentials (MEPs) were recorded from the spinal cord, sciatic nerve, or both during transcortical electrical stimulation in the rat. Four peaks could be consistently identified in the spinal MEP. The latency and amplitude of the peaks varied differentially with intensity and polarity of stimulation. Conduction velocity for Peak 1 of the MEP was 43 m/sec. Bilateral sciatic nerve MEPs were present after unilateral cortical stimulation. The spinal MEP was elicited by stimulation of areas outside the motor cortex, and the response persisted during subcortical stimulation and after motor cortex ablation. We present evidence suggesting that components of the spinal MEP in rats arise from pathways outside the motor cortex.     

Improved neuropsychological outcome in children with brain tumors diagnosed during infancy and treated without cranial irradiation.

Neuropsychological outcome of 28 patients with brain tumors diagnosed before the age of 36 months (mean, 19 months) was assessed using a comprehensive battery of tests. Elapsed time between diagnosis and testing averaged 6.2 years. Half the patients had received cranial radiation therapy and surgery, with and without chemotherapy, whereas the rest had received only surgery, with or without chemotherapy. Groups were comparable with respect to tumor diagnosis and location, age at diagnosis, race, and sex. Intellectual functioning was significantly lower in children whose treatment included cranial irradiation than in those treated without cranial irradiation, and this effect was more pronounced in nonverbal than in verbal intellectual abilities. Mean scores for the radiation group were lower than for the no-radiation group in all areas assessed and were significantly below age-based normative means in five of the eight cognitive areas: intellectual, memory, attention, motor, and visual-spatial skills. Mean scores for children in the no-radiation group were generally within the average range in all cognitive areas except visual-spatial skills, which were significantly below age-based normative means. Endocrine deficiencies and growth retardation were much more prevalent in patients treated with cranial irradiation. Because the immature brain is susceptible to treatment-related pathologic changes, infants are at greater risk than older children for significant, long-term neuropsychological, endocrine, and growth sequelae. In children treated without cranial irradiation, morbidity was minimized without an increased rate of mortality.     

Development of a fetal circadian rhythm after disruption of the maternal circadian system

The role of maternal circadian rhythms in the development of the fetal circadian system was investigated in the rat. Pregnant females were subjected to procedures known to disrupt circadian function, ablation of the maternal suprachiasmatic nuclei (SCN) or housing in constant illumination, on gestational day 10. Circadian function was assessed in fetuses at gestational day 22 by analysis of glucose utilization in hypothalamic slices in vitro using the 2-deoxyglucose method. Fetuses from control females exhibit a robust rhythm in glucose utilization in the SCN. In contrast, the SCN of fetuses from females with SCN lesions, or housed in constant illumination, show no significant day-night difference in glucose utilization. Analysis of individual brains indicates, however, that this apparent disruption in the development of circadian rhythmicity in metabolism in the fetal SCN is due to a desynchronization of individual fetuses resulting from the loss of maternal entraining influences. Thus, the fetal SCN is capable of developing a circadian rhythm in glucose utilization independent of the maternal circadian system.     

Tics moderate treatment outcome with sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: The presence of a comorbid tic disorder may predict a poorer outcome in the acute treatment of pediatric obsessive-compulsive disorder (OCD). METHODS: Using data from the National Institute of Mental Health (NIMH)-funded Pediatric OCD Treatment Study (POTS) that compared cognitive-behavior therapy (CBT), medical management with sertraline (SER), and the combination of CBT and SER (COMB), to pill placebo (PBO) in children and adolescents with OCD, we asked whether the presence of a comorbid tic disorder influenced symptom reduction on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) after 12 weeks of treatment. RESULTS: Fifteen percent (17 of 112) of patients exhibited a comorbid tic disorder. In patients without tics, results replicated previously published intent-to-treat outcomes: COMB > CBT > SER > PBO. In patients with a comorbid tic disorder, SER did not differ from PBO, while COMB remained superior to CBT and CBT remained superior to PBO. CONCLUSIONS: In contrast to CBT outcomes, which are not differentially impacted, tic disorders appear to adversely impact the outcome of medication management of pediatric OCD. Children and adolescents with obsessive-compulsive disorder and a comorbid tic disorder should begin treatment with cognitive-behavior therapy alone or the combination of cognitive-behavior therapy plus a serotonin reuptake inhibitor.