Propranolol and depression revisited: three cases and a review

The occurrence of major depressive episodes as complications of treatment with propranolol has been a matter of controversy. Three cases are reported of depressions meeting DSM-III criteria following administration of propranolol for medical conditions. Possible relationships between beta blockade and affective illness are discussed.     

Recommendations for incorporating palliative care education into the acute care hospital setting.

This article presents recommendations for improving the education of physicians about end-of-life care in the acute care hospital setting. The authors, who have a variety of backgrounds and represent several types of institutions, formulated and reached consensus on these recommendations as members of the Acute Care Hospital Working Group, one of eight working groups convened at the National Consensus Conference on Medical Education for Care Near the End of Life in May 1997. A recently published literature review on the status of palliative care education, a summary of recent research on education about end-of-life care, and expert opinion were helpful in developing the recommendations. The authors emphasize that the acute care setting offers many opportunities for education about care at the end of life. Faculty should support learners' appreciation of the importance of end-of-life care, and convey the meaning and privilege of attending to patients and families at this difficult time. Faculty should teach students and residents to provide care that embodies attention to the control of distressing physical, physiologic, and spiritual symptoms, appropriate awareness of patients' differing cultural backgrounds and their impact upon the experience of dying, excellent communication skills, the application of bioethical principles, timely referral and smooth transition to other care settings that meet patient and family goals, and the role of the interdisciplinary team in meeting the diverse needs of dying patients and their families.     

Modulation of gastrointestinal function by MuDelta,a mixed μ opioid receptor agonist/ μ opioid receptor antagonist

BACKGROUND & PURPOSE

Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound (‘MuDelta’), could normalize GI motility without constipation.

EXPERIMENTAL APPROACH

MuDelta was characterized in vitro as a potent µ opioid receptor agonist and high-affinity δ opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic δ opioid receptor immunoreactivity was quantified.

KEY RESULTS

δ Opioid receptor antagonism opposed µ opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically-mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated δ opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post-inflammatory model.

CONCLUSIONS AND IMPLICATIONS

MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome.     

Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and thrombopoiesis through the PI3K/AKT pathway

Background

Dozens of Traditional Chinese Medicine (TCM) formulas have been used for promotion of "blood production" for centuries, and we are interested in developing novel thrombopoietic medicines from these TCMs. Our previous studies have demonstrated the hematopoietic effects of DangGui BuXue Tong (DBT), a formula composed of Radix Angelicae Sinensis and Radix Astragali in animal and cellular models. As a step further to identify and characterize the active chemical components of DBT, we tested the hematopoietic and particularly, thrombopoietic effects of polysaccharide-enriched fractions from the root of Radix Angelicae Sinensis (APS) in this study.

Methods

A myelosuppression mouse model was treated with APS (10 mg/kg/day). Peripheral blood cells from APS, thrombopoietin and vehicle-treated samples were then counted at different time-points. Using the colony-forming unit (CFU) assays, we determined the effects of APS on the proliferation and differentiation of hematopoietic stem/progenitor cells and megakaryocytic lineages. Using a megakaryocytic cell line M-07e as model, we analyzed the cellular apoptosis progression with and without APS treatment by Annexin V, Mitochondrial Membrane Potential and Caspase 3 assays. Last, the anti-apoptotic effect of APS on cells treated with Ly294002, a Phosphatidylinositol 3-Kinse inhibitor (PI3K) was also tested.

Results

In animal models, APS significantly enhanced not only the recovery of platelets, other blood cells and their progenitor cells, but also the formation of Colony Forming Unit (CFU). In M-07e cells, we observed the anti-apoptotic effect of APS. Treatment by Ly294002 alone increased the percentage of cells undergoing apoptosis. However, addition of APS to Ly294002-treated cells significantly reduced the percentage of cells undergoing apoptosis.

Conclusions

APS promotes hematopoiesis and thrombopoiesis in the mouse model. This effect likely resulted from the anti-apoptosis activity of APS and is likely to involve the PI3K/AKT pathway.     

Psychostimulant treatment of depressive disorders secondary to medical illness

Hospital charts were reviewed for 66 medical and surgical patients who received dextroamphetamine or methylphenidate to treat a depressive disorder. Approximately three-fourths showed some improvement; in half of the sample, improvement was marked or moderate. Of those who improved, 93% reached their peak response within the first 2 days. Relapse occurred in only 5 patients. Side effects were minimal. Nonsignificant trends suggested that dextroamphetamine was more effective for major depression than adjustment disorder, while methylphenidate tended to be more effective for adjustment disorder. Psychostimulants appear to be a therapeutic option in the medically ill depressed population and may be more rapidly effective with fewer side effects than tricyclic antidepressants.     

Palpable prostatic nodules: comparison of US and digital guidance for fine-needle aspiration biopsy

This study was undertaken to evaluate the use of transrectal sonographically guided fine-needle aspiration biopsy and to compare sonographic with digital guidance for biopsy. In 62 patients in whom prostatic carcinoma was suspected at digital rectal examination, fine-needle aspiration biopsies were performed transperineally under sonographic guidance and transrectally under digital guidance. These patients had 89 nodules, 73 of which were sampled with both techniques. Malignant cells were obtained under digital guidance in 17 of 73 nodules (23%) and under sonographic guidance in 16 (22%). An additional seven nodules, which were not seen sonographically, were sampled under digital guidance and proved to be negative. In nine other nodules that were nonpalpable and evident only with sonography, malignant cells were obtained under sonographic guidance in three. These findings indicate that sonographic guidance for fine-needle aspiration biopsy is as good as digital guidance for palpable lesions.     

Power frequency magnetic fields do not contribute to transformation of JB6 cells

The potential for power frequency magnetic fields to enhance neoplastic transformation has been investigated in vitro using promotion-sensitive mouse epidermal JB6 cells. In a soft agar assay, 60-Hz magnetic fields of 0.01, 0.1, 1.0, or 1.1 mT flux density did not induce anchorage- independent growth. In addition, these magnetic fields did not enhance tumor promoter-induced transformation showing no increase in the maximum number of transformed colonies and no shift in the dose- response curve. Thus, these data do not support the notion that environmental exposures to magnetic fields contribute to transformation.