A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Synthesis and analgesic properties of new 5-thioaryl pyrazole derivatives

A new series 5-thio aryl pyrazole derivatives were proposed aiming analgesic activity. In this work, 8 new compounds of this class were synthesized using usual synthetic methodology, having as key intermediate the 3-methyl-4-nitro-5-chloropyrazole-1-phenyl derivative and subsequent reaction with several nucleophiles sulfides. Pharmacological evaluation of this series showed analgesic activity in the some extent in especially for 5-(4-bromophenyl)-thio-3-methyl-4-nitro-1-phenylpyrazole which was the most potent in this series, presenting an analgesic action comparable to that show by dipyrone.     

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat

BACKGROUND: We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. RESULTS: When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. CONCLUSIONS: Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.     

Fuzzy logical control based on optical information technologies

This paper is concerned with one problem in creating intellectual control systems: methods and design tools of fuzzy logical devices for building modern efficient and reliable control systems in poorly formalized problems and ill-structured problem domains. Flaws of the available microprocessor devices for fuzzy information processing are indicated and alternative design principles of fuzzy logic control systems based on high-speed spatially distributed wave guide optical structures are considered based on an example of an opto-electronic dephaser. High-speed spatially distributed wave guide optical structures are shown as being advantageous for solving the scientific and engineering problems for developing new design methods of fuzzy logical devices with enhanced technical characteristics for implementation of fuzzy logical control.     

DANGERS OF LAB-PLANT SCALEUP FOR FILTERS INVOLVING SOLIDLIQUID SYSTEMS

Many laboratory procedures have been used for predicting the size of clarifiers, thickeners, filters, and centrifuges or choosing the optimum quantity of filter-aid and flocculants. Scaleup predictions are frequently based on experiments involving small pressure and vacuum filters, compression-permeability cells, and sedimentation rates. Among major problems related to the accuracy of scaleup are: (1) unrepresentative sampling, (2) aging of suspensions with accompanying changes in properties of cakes and sediments, (3) effect of sedimentation not included in theoretical equations, (4) wall effects in small diameter filters and cells, and (5) misapplication of theory to experiment.     

Primary focal segmental glomerulosclerosis: clinical course and response to therapy

Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.     

The genome of Treponema pallidum: new light on the agent of syphilis

Covert brain activity related to task-free, spontaneous (i.e. unrequested), emotional evaluation of human face images was analysed in 27-channel averaged event-related potential (ERP) map series recorded from 18 healthy subjects while observing random sequences of face images without further instructions. After recording, subjects self-rated each face image on a scale from "liked" to "disliked". These ratings were used to dichotomize the face images into the affective evaluation categories of "liked" and "disliked" for each subject and the subjects into the affective attitudes of "philanthropists" and "misanthropists" (depending on their mean rating across images). Event-related map series were averaged for "liked" and "disliked" face images and for "philanthropists" and "misanthropists". The spatial configuration (landscape) of the electric field maps was assessed numerically by the electric gravity center, a conservative estimate of the mean location of all intracerebral, active, electric sources. Differences in electric gravity center location indicate activity of different neuronal populations. The electric gravity center locations of all event-related maps were averaged over the entire stimulus-on time (450 ms). The mean electric gravity center for disliked faces was located (significant across subjects) more to the right and somewhat more posterior than for liked faces. Similar differences were found between the mean electric gravity centers of misanthropists (more right and posterior) and philanthropists. Our neurophysiological findings are in line with neuropsychological findings, revealing visual emotional processing to depend on affective evaluation category and affective attitude, and extending the conclusions to a paradigm without directed task.     

The dental status of asthmatic British school children

Pancreatic cancer is a dismal disease. The 5-year overall survival ranges from 1% to 5%. Surgery is the only curative treatment available for this cancer, but it is indicated only in selected patients with a less than 4 cm tumor. In these patients, survival rate is about 30%. We have considered several aspects: the very difficult early diagnosis, the correct diagnostic flow chart, actual surgical procedures and new trends in biologic and genetic research. It is likely that better results can be achieved by defining an "early pancreatic cancer" and establishing how to detect it. This could be the wrigth one way is to significantly improve the survival of these patients.     

Fetal heart rate patterns in postasphyxiated fetal lambs with brain damage

OBJECTIVE: We previously showed that in asphyxiated fetal lambs the duration of hypotension correlated well with the severity of histologic damage to the brain, whereas the duration of bradycardia did not. This study compares fetal heart rate patterns with the degree of histologic damage to the brain. STUDY DESIGN: Twelve chronically instrumented near-term fetal lambs were subjected to asphyxia by umbilical cord occlusion until fetal arterial pH was <6. 9 and base excess was <-20 mEq/L. An additional 4 fetuses served as sham-asphyxia controls. Fetal heart rate (from electrocardiogram), arterial blood pressure, fetal breathing movements, and electrocorticogram were continuously monitored before, during, and for 72 hours after asphyxia. Fetal brain histologic features were categorized as mild (group 1, n = 5), moderate (group 2, n = 4), and severe (group 3, n = 3). Long-term fetal heart rate variability expressed as amplitude range was assessed visually every 5 minutes from 30 minutes before asphyxia until 2 hours of recovery and at 6, 12, 24, 48, and 72 hours of recovery. RESULTS: Long-term fetal heart rate variability amplitude decreased from 32 +/- 17 beats/min (mean +/- SEM) preocclusion to 4 +/- 13 beats/min at the end of occlusion (P <.001) without significant differences among the 3 groups. During 10 to 45 minutes of recovery, the long-term variability of group 1 was significantly greater than that of groups 2 and 3. At 24 to 72 hours of recovery, the long-term variability of groups 1 and 2 was significantly higher than that of group 3, which was almost 0. The "checkmark" and sinusoidal fetal heart rate patterns were observed during the recovery period in groups 2 and 3. CONCLUSIONS: Decreased long-term fetal heart rate variability and the "checkmark" and sinusoidal fetal heart rate patterns were indicators of the severity of asphyxial histologic damage in the fetal brain.