Quantitative analysis of the olfactory pathway for drug delivery to the brain

Following intranasal administration to rats, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) concentrated in the olfactory nerve and glomerular layers of the olfactory bulb resulting in a mean olfactory bulb concentration of 140 nM. A negligible amount of label was detected in the olfactory bulb following intravenous administration of WGA-HRP or intranasal administration of unconjugated HRP. This is the first quantitative assessment of intraneuronal transport of a protein into the brain using the olfactory route.     

Initial brain metastasis velocity: does the rate at which cancers first seed the brain affect outcomes?

Purpose/objective(s)

Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). A limitation in the application of BMV is it cannot be applied until time of first BM failure after SRS. We developed initial BM velocity (iBMV), a new metric that accounts for the number of BM at first SRS and the time since initial cancer diagnosis.

Materials/methods

We reviewed patients with BM treated at our institution with upfront SRS without WBRT. iBMV was calculated as the number of BM at initial SRS divided by time (years) from initial cancer diagnosis to first SRS. We performed a linear regression to correlate BMV as a continuous variable and with low, intermediate, and high BMV risk groups. Kaplan–Meier estimation of OS was calculated from time of first SRS to death. iBMV was not calculated for patients who presented with BM at initial cancer diagnosis.

Results

994 patients were treated with upfront SRS without WBRT between 2000 and 2017. Median OS was 8.5 mos. 595 (60%) patients developed BM after cancer diagnosis and median time to first SRS from time of initial diagnosis was 2.2 years. Median iBMV was 0.79 BM/year. iBMV correlated with BMV (β?=?1.57 p?=?0.021) and independently predicted for mortality [Cox proportional hazard ratio (HR) 1.11, p?=?0.036] after accounting for histology, number of initial brain metastases (HR 1.03, p?=?0.32), time from cancer diagnosis to SRS (HR 0.98, p?=?0.157) in a multivariate model.

Conclusion

iBMV correlates with BMV and OS. With further validation, iBMV could serve as a metric to risk stratify patients for WBRT or SRS at time of first BM presentation.

     

Computerized scintigraphic technique for the evaluation of adult respiratory distress syndrome: initial clinical trials

Eleven patients with suspected adult respiratory distress syndrome (ARDS) and five control patients were studied using a computerized gamma imaging and analysis technique and 99mTc-labeled human serum albumin. The heart and right lung were imaged, lung:heart ratio was plotted vs. time, and a linear regression was fitted to the data points displayed. The slope of this fit was termed the "slope index." An index value of 2 standard deviations greater than the control mean was considered positive. Radiographs from the six positive studies revealed typical diffuse air-space disease. Radiographs from two of the five negative studies demonstrated air-space consolidation. Both of these patients had elevated pulmonary capillary wedge pressure, cardiomegaly, and clinical course consistent with cardiogenic pulmonary edema. These preliminary data demonstrated a good correlation between positive slope index and clinical ARDS.     

Young children's views of stressful life events

Fourth through 6th grade urban and suburban children first judged how upsetting they thought each of 22 stressful life events would be if the events occurred to age-mates (“cognitive” set). The children then checked events they had actually experienced and rated each in terms of how upsetting it was for them (“experiential” set). Low-level consistencies were found among judged cognitive upset ratings for the 22 items. The latter formed three factors reflecting loss events getting into trouble, and change in living situation. Although there were significant relationships between judged cognitive and experiential upset ratings for the 22 events, absolute levels of judged upset were consistently higher under the cognitive set.