CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer.

BACKGROUND: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. PATIENTS AND METHODS: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. RESULTS: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. CONCLUSION: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.

The genetic basis of speciation in the Giliopsis lineage of Ipomopsis (Polemoniaceae).

One of the most powerful drivers of speciation in plants is pollinator-mediated disruptive selection, which leads to the divergence of floral traits adapted to the morphology and behavior of different pollinators. Despite the widespread importance of this speciation mechanism, its genetic basis has been explored in only a few groups. Here, we characterize the genetic basis of pollinator-mediated divergence of two species in genus Ipomopsis, I. guttata and I. tenuifolia, using quantitative trait locus (QTL) analyses of floral traits and other variable phenotypes. We detected one to six QTLs per trait, with each QTL generally explaining small to modest amounts of the phenotypic variance of a backcross hybrid population. In contrast, flowering time and anthocyanin abundance (a metric of color variation) were controlled by a few QTLs of relatively large effect. QTLs were strongly clustered within linkage groups, with 26 of 37 QTLs localized to six marker-interval 'hotspots,' all of which harbored pleiotropic QTLs. In contrast to other studies that have examined the genetic basis of pollinator shifts, our results indicate that, in general, mutations of small to modest effect on phenotype were involved. Thus, the evolutionary transition between the distinct pollination modes of I. guttata and I. tenuifolia likely proceeded incrementally, rather than saltationally.

Recovery from inhalation of diquat aerosol.

A patient developed high fever, cough, changing consolidations on chest roentgenograms, jaundice, and skin rash following inhalation of diquat aerosol. To our knowledge this is the first report of diquat inhalation and only the second report of aerosol damage from any part of the dipyridyl herbicides.

Proton magnetic resonance imaging to stage activity of interstitial lung disease.

Patients with active interstitial lung disease (ILD) are often treated with high-dose corticosteroids, although such therapy is not universally effective and has significant risks. Clinicians have utilized various ancillary diagnostic techniques to help with difficult treatment decisions. Since magnetic resonance imaging (MRI) has the theoretic and experimental potential of differentiating various stages of ILD, we prospectively studied 34 adult patients in a 0.15 Tesla resistive magnet body imager. The most severely affected patients, who were thought to warrant a steroid trial, had the greatest MRI image intensity, and dramatic improvement was seen following successful treatment. Qualitative MRI data were as useful as any other ancillary diagnostic technique (radiographic, physiologic, scintigraphic) in predicting clinical course. Computer-generated relaxation times were not sufficiently precise to differentiate active from inactive disease. Although limited by availability and cost, MRI appears to be a useful ancillary diagnostic technique in ILD patients facing immunomodulating therapy.

Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice.

STUDY OBJECTIVE: To compare quality of life and exercise capacity (primary aim), and drug usage (secondary aim), between groups of patients with irreversible chronic airflow limitation (CAL) who were undergoing theophylline Theo-Dur; Key Pharmaceuticals; Kenilworth, NJ) therapy guided by n of 1 trials or standard practice. DESIGN: Randomized study of n of 1 trials vs standard practice. SETTING: Outpatient departments in two tertiary care centers. PATIENTS: Sixty-eight patients with irreversible CAL who were symptomatic despite the use of inhaled bronchodilators, and who were unsure whether theophylline was helping them following open treatment, were randomized into n of 1 trials (N=34) or standard practice. INTERVENTIONS: The n of 1 trials (single-patient, randomized, double-blind, multiple crossover comparisons of the effect on dyspnea of theophylline vs a placebo) followed published guidelines. Standard practice patients stopped taking theophylline but resumed it if their dyspnea worsened. If their dyspnea then improved, theophylline was continued. In both groups, a decision about continuing or stopping the use of theophylline was made within 3 months of randomization. MEASUREMENTS AND RESULTS: The primary outcomes (the chronic respiratory disease questionnaire [CRQ] and 6-min walk) were measured at baseline, 6 months, and 12 months by personnel blinded to treatment group allocation. No between-group differences (n of 1 minus standard practice) were seen in within-group changes over time (1 year minus baseline) in the CRQ Physical Function score (point estimate on the difference, -2.8; 95% confidence limits [CLs], -8.2, 2.5), CRQ Emotional Function score (point estimate on the difference, 0.5; 95% CLs, -4.7, 5.7), or 6-min walk (point estimate on the difference, 8 m; 95% CLs, -26, 44 m). No differences between groups were seen in the secondary outcome of the proportion of patients taking theophylline at 6 and 12 months. In 7 of 34 n of 1 trial patients (21%), dyspnea improved during theophylline treatment compared with placebo treatment. CONCLUSIONS: Using n of 1 trials to guide theophylline therapy in patients with irreversible CAL did not improve their quality of life or exercise capacity, or reduce drug usa e, over 1 year compared to standard practice. Under the objective conditions of an n of 1 trial, 21% of patients with CAL responded to theophylline. There remains a rationale for considering theophylline in patients with irreversible CAL who remain symptomatic despite the use of inhaled bronchodilators, but the use of n of 1 trials to guide this decision did not yield clinically important advantages over standard practice.

Locomotor activity in morphine-treated rats: effects of and comparisons between cocaine, procaine, and lidocaine.

The effects of cocaine, procaine, and lidocaine on open field and spontaneous (actophotometer) locomotor activities were assessed and compared in rats (1) treated acutely with morphine (single injection), (2) made dependent on morphine (SC pellets), (3) implanted with morphine and withdrawn at the time of peak dependence, and (4) implanted SC with lactose-containing pellets (sham). Cocaine-induced (10 or 30 mg/kg) open field and spontaneous locomotor activities were significantly greater in each of the four groups than those of the corresponding groups administered saline. Procaine (50 or 100 mg/kg) significantly reduced open field locomotor activity in all morphine-treated rats and spontaneous locomotor activity in acute rats. Lidocaine (30 mg/kg) significantly depressed spontaneous locomotor activity in acute rats. Upon comparison of the activities induced by the three local anesthetics, open field locomotor activity of sham-implanted rats was greater following cocaine (10 or 30 mg/kg) than following procaine (50 or 100 mg/kg). Only morphine withdrawn rats manifested greater activity following cocaine (10 mg/kg) than following either procaine (50 mg/kg) or lidocaine (10 mg/kg); activities were equivalent in dependent and acute rats. In contrast, cocaine-induced (30 mg/kg) open field locomotor activity of all morphine-treated rats was greater than either procaine- (100 mg/kg) or lidocaine- (30 mg/kg) induced activities. Spontaneous locomotor activity of all groups except acute morphine was greater following both doses of cocaine than following both doses of either procaine or lidocaine. In acute rats, only cocaine (10 mg/kg, induced greater activity than the other local anesthetics. Thus, stimulation of locomotor activity following cocaine treatment is a pharmacological property unique to cocaine and not shared by either procaine or lidocaine. Further, the data indicate that the methods selected for assessing locomotor activity may not give comparable results.

The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications.

The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO(3))(2)/0.04 M H(3)PO(4).12MoO(3)/4M HNO(3) solution that were heated to 200 degrees C under argon were found to have the best overall performance of the samples studied in this work.

Mediastinal lymph-node biopsy is a definitive staging procedure for bronchogenic carcinoma.

Mediastinal lymph-node biopsy has been performed as a staging procedure in most cases of bronchogenic carcinoma since 1965. This study was carried out to assess the results of staging by this method in 75 patients. Biopsy sites were marked with hemoclips. Three zones were defined: zone 3 (inoperable), beyond the midline and above the lower border of the aortic arch; zone 1 (operable), more than 3 cm from the carcinoma, ipsilateral to the tumour; and zone 2, between zones 1 and 3. Forty of 75 patients had biopsy specimens showing carcinoma. The proportion was highest in small cell anaplastic carcinoma and lowest in squamous cell tumours. Of the 40 positive biopsies 35 were from zone 3. All the positive biopsy specimens showing small cell anaplastic carcinoma were from zone 3. Positive specimens correlated strongly with other evidence of inoperability. Mediastinal lymph-node biopsy is a definitive staging procedure.

The application of 67Ga scanning in determining the operability of bronchogenic carcinoma.

In a prospective study of 34 patients with histologically proven bronchogenic carcinoma, 67Ga scanning of the chest was used to screen for mediastinal involvement. Mediastinal scans and pathologic findings were in agreement in 27 patients. Two patients had false-negative scans and 5 had positive scans but no evidence of mediastinal tumor. These results indicate a sensitivity of 89%, a specificity of 66.6%, an accuracy of 77% for positive scans, and an accuracy of 83% for negative scans. Overall correlation between 67Ga scanning of the chest and mediastinal-tumor involvement is statistically significant (P = 0.003).