Intracerebral P3-like waveforms and the length of the stimulus-response interval in a visual oddball paradigm.

OBJECTIVE: This study investigated the possible linkage of intracerebrally recorded P3-like waveforms to the processes induced by stimulus perception or motor response formation. METHODS: Event-related potentials were recorded from 560 cerebral sites in 17 patients suffering from intractable epilepsy during visual oddball task. Potentials evoked by the target stimuli were sorted according to button-pressing response times, and the P3 waveform was analyzed both in stimulus-locked and response-locked averages, which were separately averaged for fast and slow responses. RESULTS: P3-like waveforms were identified in 180 sites in 17 patients. Three different types of P3-like waveforms, diffusely distributed within the brain, were found: (1) time-locked to the stimulus (30 sites in 11 patients); (2) time-locked to the motor response (52 sites in 13 patients); and (3) with ambiguous time relationship to stimulus and motor response (98 sites in 16 patients). CONCLUSIONS: The intracerebral P3-like waveform could represent different processes involved in performing active oddball tasks. Therefore, our results support the hypothesis that the P3 waveform registered by surface electrodes could be a heterogeneous phenomenon. SIGNIFICANCE: These results provide evidence that the P3 waveform is not only related to stimulus processing, which differs from what has been generally claimed in the literature.     

Functional Characteristics of Human Trophoblast Interferons

Human trophoblast populations from first- and third-trimester placentas produce interferons (IFNs) in the presence of growth factors (CSF and PDGF) or when infected with virus. The highly invasive extravillous trophoblast population produced a higher level of IFNs (three- to eightfold, P < 0.05) than the noninvasive villous trophoblast population when stimulated with growth factors and/or virus. The level of IFN produced was dependent on the type of trophoblast population, the type of inducer and the stage of differentiation of the trophoblasts. Tandem immunoaffinity chromatography of the virus-induced trophoblast IFNs resulted in the isolation of trophoblast IFN-α and -β types. The purified trophoblast IFNs have antiviral, antiproliferative and immunoregulatory properties. Furthermore, the trophoblast IFNs inhibited the expression of proto-oncogenes such as EGF-R, c-erbB2 and c-fms reported to be involved in normal trophoblast growth and differentiation. These data suggest essential roles of interferons in normal human development during pregnancy.     

Phase I evaluation of spirogermanium and 5-fluorouracil in colorectal carcinoma

We have conducted a phase I study to evaluate the toxicity and tolerance of a 5 day continuous infusion of spirogermanium and 5-fluorouracil, (5-FU). The 5-FU was administered via a peripheral vein at 1000 mg/M²/day for 5 days by continuous infusion. Simultaneously, spirogermanium was administered via an indwelling central venous catheter by continuous infusion for 5 days starting at 50 mg/M²/day and escalating to 250 mg/M²/day. Sixteen patients received a total of 54.5 courses of therapy. The most common and severe toxicity was neurotoxicity. Mild to moderate gastrointestinal toxicity also occurred. No significant hematologic toxicity occurred. Two partial responses occurred lasting 11 and 20.5 months, both at the 100 mg/M²/day level of spirogermanium. The recommended phase II dosages are 5-FU 1000 mg/M²/day and spirogermanium 200 mg/M²/day by 5 day continuous infusion with escalation of the spirogermanium in selected individuals. Patients on long term therapy should have close neurologic evaluation and follow up. Consideration should also be given to evaluating a group of patients at the 100 mg/M²/day level of spirogermanium due to the responses seen at this level.Presented in part at the 79th annual meeting of the American Association for Cancer Research, May 1988, New Orleans, LA, USA.     

Comparison of survival in continuous ambulatory peritoneal dialysis and hospital haemodialysis: a multicentric study

We compared the survival of 842 patients on centre haemodialysis to 272 patients on continuous ambulatory peritoneal dialysis (CAPD). All patients selected had begun treatment between 1 January 1984 and 30 June 1988 and were from six centres which participate in a regional renal patients registry. Patients on CAPD were older and had a greater proportion of diabetes and other associated diseases. Age, diabetes, and cardiovascular diseases were associated with a shorter survival on treatment in all the patients studied. Without adjustment for risk factors, patient 3-year survival was higher in centre haemodialysis than in CAPD, 80% versus 64% respectively. However, no significant differences could be shown in the survival rates of the two treatment modalities after accounting for the heterogeneity of the patients in the two groups, either by stratification or by multivariate analysis (Cox). Age was the main predictive factor for CAPD patient survival, while the influence of diabetes and cardiovascular diseases was less clear. Technique survival was much better in centre haemodialysis (94% versus 56% in CAPD, 3-year survival). Older age and diabetes mellitus were associated with a greater risk of switching from centre haemodialysis to CAPD and a trend to retain those patients on CAPD.     

Lactic acidosis in children with acute exacerbation of severe asthma.

This is a retrospective case series reporting lactic acidosis in four pediatric patients with acute severe asthma treated with nebulized beta2-agonists in a pediatric intensive care unit of a tertiary care teaching facility. During treatment with beta2-agonists, these patients developed lactic acidosis with a peak concentration of 5.2 to 13 mmol/l. Lactic acidosis improved within 24 h after discontinuation or decrease in the dosage of beta2-agonists. We conclude that the intensive use of beta2-agonists for acute severe asthma in children may be the primary and significant cause of lactic acidosis.     

Selected metabolic parameters and the risk for uterine fibroids.

OBJECTIVE: To analyze the possible association between insulin resistance and dyslipidemia with uterine fibroids, using objective metabolic measurements. METHOD: A cross-sectional study of 56 women with uterine fibroids (case group) and 20 women without fibroids (control group). Levels of fasting glucose, insulin, C-peptide, sex hormone-binding globulin, and the lipid panel were measured. The short insulin tolerance test was performed. Body mass index, atherogenic index, and the indicator of insulin resistance (Kitt) were also calculated. RESULTS: Women with fibroids had significantly higher levels of serum HDL-cholesterol compared with control patients (1.8+/-0.3 vs 1.6+/-0.5; P<0.05). Women with fibroids aged 30-45 years had significantly lower LDL-cholesterol levels than comparative control patients (2.9+/-0.7 vs 3.4+/-0.9; P<0.05). A positive correlation between volume of the largest fibroid and serum HDL-cholesterol level was found in women aged 30-45 years. There were no differences in indicators of insulin resistance between the groups. CONCLUSION: Insulin resistance was not shown to be a risk factor for fibroids. There is a negative association between some parameters of metabolic syndrome and fibroid volume.     

Adaptive biological image-guided IMRT with anatomic and functional imaging in pharyngo-laryngeal tumors: impact on target volume delineation and dose distribution using helical tomotherapy.

BACKGROUND AND PURPOSE: Adaptive image-guided IMRT appears to be a promising approach for dose escalation in pharyngo-laryngeal tumors. In this framework, we assessed in a proof of concept study the impact of anatomic and functional imaging modalities acquired prior and during radiotherapy on the target volume delineation and the dose distribution using helical tomotherapy. MATERIALS AND METHODS: Ten patients with pharyngo-laryngeal squamous cell carcinoma were treated by concomitant chemo-radiation delivered in 7 weeks. CT, T2-MRI, fat suppressed T2-MRI, and static and dynamic FDG-PET were acquired for each patient before the start of treatment and during radiotherapy, after mean prescribed doses of 14, 25, 35 and 45 Gy. GTVs were manually delineated on CT and MRI images while PET images were automatically segmented by means of a gradient-based method. From these volumes, CTVs and PTVs were derived using consistent guidelines. Simultaneous integrated boost IMRT planning was performed using helical tomotherapy. RESULTS: GTVs significantly decreased throughout the course of RT for all imaging modalities (p<0.001). Clinically non-significant differences and high correlations were found between GTVs delineated on CT and MRI, irrespective of the sequence used. By contrast, FDG-PET-based GTVs segmented from pre- and per-treatment images were significantly smaller compared to anatomical imaging modalities, without any difference existing between static and dynamic acquisition. These differences in GTVs translated into parallel reductions of both prophylactic and therapeutic CTVs and PTVs. Resulting FDG-PET-based and adaptive IMRT planning reduced the irradiated volumes by 15-40% compared to pre-treatment CT planning (V(90), V(95) and V(100)), but did marginally impact on doses to the OAR such as the spinal cord and the parotid glands. CONCLUSIONS: Adaptive IMRT with FDG-PET images has a significant impact on the delineation of TVs and on the dose distribution in pharyngo-laryngeal tumors. Such an approach might thus be considered for dose escalation strategies.