Distinct deoxyribonucleic acid polymerase activities associated with Dane particles and naked Dane cores.

Two distinct deoxyribonucleic acid polymerase activities were found associated with liver fractions containing Dane particles and Dane cores.     

ATP: an extracellular signaling molecule between neurons and glia

Recent studies on Schwann cells at the neuromuscular junction and non-synaptic regions of premyelinated axons indicate that extracellular ATP can act as an activity-dependent signaling molecule in communication between neurons and glia. Several mechanisms have been observed for the regulated release of ATP from synaptic and non-synaptic regions, and a diverse family of receptors for extracellular ATP has been characterized. The findings suggest functional consequences of neuron–glial communication beyond homeostasis of the extracellular environment surrounding neurons, including regulating synaptic strength, gene expression, mitotic rate, and differentiation of glia according to impulse activity in neural circuits.     

Spatial and temporal variation of microstimulation thresholds for inhibiting the tail-flick reflex from the rat's rostral medial medulla.

Suppression of the tail-flick reflex by microstimulation of the rostral medial medulla in rats lightly anesthetized with barbiturates was studied with regard to spatial and temporal variations in electrical threshold. Trains of constant-current pulses with linearly descending amplitudes (called 'ramps') were passed through the extracellular brain microelectrode during noxious heating of the tail. The pulse amplitude at the time of the reflex, after allowance for conduction and reaction latencies, was taken as the threshold reading. This new method revealed a range of vertical electrode positions corresponding roughly to the nucleus raphe magnus, where the thresholds tended to be lowest (a mean of 4.1 microA for 0.4-ms pulses delivered at 50 Hz). In confirmation of the technique's validity neither the duration of the ramp nor its starting amplitude, within their useful range, significantly affected the measured threshold. Pronounced temporal fluctuation was seen in thresholds measured every 2 min. Spatial variability within the low-threshold region and differences between preparations were statistically much smaller sources of variation. The temporal fluctuation appeared to have a stationary mean for at least 20 min under constant conditions of anesthesia. In some experiments, action potentials from single neurons were recorded through the stimulating electrode, and classified into those inhibited during the tail-flick (off-cells), those excited (on-cells), and those unaffected (neutral cells). The thresholds where off-cells exhibited their maximum action potential were on average significantly lower than corresponding thresholds for on-cells. Short-range (less than 0.2 mm) spatial variations in the threshold appeared however to be uncorrelated with the distance to an individual recorded off-cell or on-cell.(ABSTRACT TRUNCATED AT 250 WORDS)     

How I treat adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I. ATL carries a bad prognosis because of intrinsic chemoresistance and severe immunosuppression. In acute ATL, Japanese trials demonstrated that although combinations of chemotherapy improved response rate, they failed to achieve a significant impact on survival. Patients with chronic and smoldering ATL have a better prognosis, but long-term survival is poor when these patients are managed with a watchful-waiting policy or with chemotherapy. Recently, a worldwide meta-analysis revealed that the combination of zidovudine and IFN-α is highly effective in the leukemic subtypes of ATL and should be considered as standard first-line therapy in that setting. This combination has changed the natural history of the disease through achievement of significantly improved long-term survival in patients with smoldering and chronic ATL as well as a subset of patients with acute ATL. ATL lymphoma patients still benefit from chemotherapy induction with concurrent or sequential antiretroviral therapy with zidovudine/IFN. To prevent relapse, clinical trials assessing consolidative targeted therapies such as arsenic/IFN combination or novel monoclonal antibodies are needed. Finally, allogeneic BM transplantation should be considered in suitable patients.     

The Role of Nitric Oxide in Ethanol-Induced Gastrointestinal Dysfunction

We recently showed that acute ethanol inhibits contractility of the lower esophageal sphincter (LES) and the lower esophageal body (LEB) both in vivo and in vitro. To evaluate the mechanism of this inhibitory effect of ethanol, we investigated the role of nitric oxide (NO) on contractility of isolated LES and LEB circular muscle strips using inhibitors of NO synthase (NOS), N ^G-itro- l -arginine methyl ester and N ^G-nitro- l -arginine. Ethanol significantly decreased LES basal tone. This effect was not mediated by NO, because inhibition was not prevented by inhibitors of NOS. Electrical field stimulation caused an On-response relaxation from LES strips, and an Off-response contraction from both LES and LEB strips. Inhibitors of NOS prevented the On-response relaxation of LES, but had no significant effect on LES Off-response contraction. Ethanol potentiated the On-response relaxation of the LES Off-response contraction. Ethanol potentiated the On-response relaxation of LES, but had no significant effect on Off-response contraction. Ethanol's potentiating effect of the On-response relaxation is NO-mediated, because it was abolished by NOS inhibitors. Ethanol also inhibited carbachol-induced LES contractility. This inhibitory effect was NO-mediated, because NOS inhibitors abolished it. Ethanol inhibited both the Off-response contraction and carbachol-induced contraction of LEB strips. These effects were not NO-mediated, because they were not affected by NOS inhibitor. These data suggest that NO is not a mediator for the inhibitory effect of ethanol on LEB contractility, and that NO seems to be a mediator of ethanol inhibition of some aspects of LES motor functions.     

Decrease in central venous catheter placement due to use of ultrasound guidance for peripheral intravenous catheters

Study Objectives

Obtaining intravenous (IV) access in the emergency department (ED) can be especially challenging, and physicians often resort to placement of central venous catheters (CVCs). Use of ultrasound-guided peripheral IV catheters (USGPIVs) can prevent many “unnecessary” CVCs, but the true impact of USGPIVs has never been quantified. This study set out to determine the reduction in CVCs by USGPIV placement.

Methods

This was a prospective, observational study conducted in 2 urban EDs. Patients who were to undergo placement of a CVC due to inability to establish IV access by other methods were enrolled. Ultrasound-trained physicians then attempted USGPIV placement. Patients were followed up for up to 7 days to assess for CVC placement and related complications.

Results

One hundred patients were enrolled and underwent USGPIV placement. Ultrasound-guided peripheral IV catheters were initially successfully placed in all patients but failed in 12 patients (12.0%; 95 confidence interval [CI], 7.0%-19.8%) before ED disposition, resulting in 4 central lines, 7 repeated USGPIVs, and 1 patient requiring no further intervention. Through the inpatient follow-up period, another 11 patients underwent CVC placement, resulting in a total of 15 CVCs (15.0%; 95 CI, 9.3%-23.3%) placed. Of the 15 patients who did receive a CVC, 1 patient developed a catheter-related infection, resulting in a 6.7% (95 CI, 1.2%-29.8%) complication rate.

Conclusion

Ultrasound prevented the need for CVC placement in 85% of patients with difficult IV access. This suggests that USGPIVs have the potential to reduce morbidity in this patient population.     

Temperature measurement in pediatrics: a comparison of the rectal method versus the temporal artery method

The purpose of this study was to determine if there is a difference between temperature readings obtained using two different electronic temperature devices: one measuring temporal artery temperature (TAT) and one measuring rectal temperature (RT). A comparative single-group design was used with each participant acting as his or her control. The sample consisted of 47 pediatric patients between 3 and 36 months of age. Data analysis revealed no statistically significant differences between TAT and RT; however, concerns related to statistical significance versus clinical significance are discussed.     

B7-1 Engagement of Cytotoxic T Lymphocyte Antigen 4 Inhibits T Cell Activation in the Absence of CD28

Ligation of cytotoxic T lymphocyte antigen 4 (CTLA4) appears to inhibit T cell responses. Four mechanisms have been proposed to explain the inhibitory activity of CTLA4: competition for B7-1 and B7-2 binding by CD28; sequestration of signaling molecules away from CD28 via endocytosis; delivery of a signal that antagonizes a CD28 signal; and delivery of a signal that antagonizes a T cell receptor (TCR) signal. As three of these potential mechanisms involve functional antagonism of CD28, an experimental model was designed to determine whether CTLA4 could inhibit T cell function in the absence of CD28. TCR transgenic/recombinase activating gene 2–deficient/CD28–wild-type or CD28-deficient mice were generated and immunized with an antigen-expressing tumor. Primed T cells from both types of mice produced cytokines and proliferated in response to stimulator cells lacking B7 expression. However, whereas the response of CD28^+/+ T cells was augmented by costimulation with B7-1, the response of the CD28^−/− T cells was strongly inhibited. This inhibition was reversed by monoclonal antibody against B7-1 or CTLA4. Thus, CTLA4 can potently inhibit T cell activation in the absence of CD28, indicating that antagonism of a TCR-mediated signal is sufficient to explain the inhibitory effect of CTLA4.     

Utility of a multidisciplinary tumor board in the management of pancreatic and upper gastrointestinal diseases: an observational study

Background & objectives

Multidisciplinary tumor boards (MDTBs) are frequently employed in cancer centers but their value has been debated. We reviewed the decision-making process and resource utilization of our MDTB to assess its utility in the management of pancreatic and upper gastrointestinal tract conditions.

Racial and Ethnic Disparities in Genetic Testing at a Hereditary Breast and Ovarian Cancer Center

BackgroundPrior studies suggest that referral to genetic counseling and completion of genetic testing vary by race/ethnicity; however, the data are limited.ObjectiveWe sought to evaluate patterns of genetic testing and clinical outcomes across race/ethnicity at a hereditary breast and ovarian cancer center.DesignThe medical records for all patients undergoing genetic assessment at a hereditary breast and ovarian cancer center were reviewed and stratified by self-reported race/ethnicity (non-Hispanic White, Hispanic, non-Hispanic Black, and Asian).ParticipantsA total of 1666 patients met inclusion criteria (non-Hispanic Whites, 1367; Hispanics, 85, non-Hispanic Blacks, 101; Asians, 113).Main MeasuresDemographics, patient characteristics, and referral patterns for patients who underwent genetic testing were analyzed using Kruskal-Wallis tests, chi-square test, or Fisher’s exact tests, stratifying by self-reported race/ethnicity. Pathogenic mutations and variants of unknown significance (VUS) were reviewed. Outcomes of patients with genetic mutations and personal history of breast and/or gynecologic malignancies were compared.Key ResultsNon-Hispanic Whites were more likely to be referred due to family cancer history compared to all other ethnicities while Non-Hispanic Blacks, Hispanics, and Asians were more likely to be referred due to personal history of cancer (p < 0.001). Non-Hispanic Blacks and Hispanics were more likely to have advanced-stage cancer at the time of genetic testing (p < 0.02). Rates of mutations did not differ by race/ethnicity when Ashkenazi Jewish patients were excluded (p = 0.08). Among patients found to have a BRCA1/2 mutation, Non-Hispanic Whites were more likely to undergo cancer screening and risk-reducing surgery compared with all other ethnicities (p = 0.04).ConclusionsMinority patients were more likely to utilize genetic services following a cancer diagnosis and less likely due to family cancer history, suggesting a missed opportunity for mutation detection and cancer prevention in this population. Efforts to eradicate racial/ethnic disparities in early access to genetic testing and guided cancer prevention strategies are essential.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06064-x) contains supplementary material, which is available to authorized users.