Continuous Subcutaneous Infusion of Narcotics: An Exploratory Study of Patient,Family and Nursing Concerns

This is a briefly annotated bibliography of useful materials for the education of health professionals, principally physicians. It encompasses teaching goals, methods, and settings, as well as model courses, course evaluation, communication skills, general resources on death education, and miscellaneous background pieces.     

Membrane-associated farnesylated UCH-L1 promotes α-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is linked to Parkinson's disease (PD) and memory and is selectively expressed in neurons at high levels. Its expression pattern suggests a function distinct from that of its widely expressed homolog UCH-L3. We report here that, in contrast to UCH-L3, UCH-L1 exists in a membrane-associated form (UCH-L1^M) in addition to the commonly studied soluble form. C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum. The amount of UCH-L1^M in transfected cells is shown to correlate with the intracellular level of α-synuclein, a protein whose accumulation is associated with neurotoxicity and the development of PD. Reduction of UCH-L1^M in cell culture models of α-synuclein toxicity by treatment with a farnesyltransferase inhibitor (FTI-277) reduces α-synuclein levels and increases cell viability. Proteasome function is not affected by UCH-L1^M, suggesting that it may negatively regulate the lysosomal degradation of α-synuclein. Therefore, inhibition of UCH-L1 farnesylation may be a therapeutic strategy for slowing the progression of PD and related synucleinopathies.     

Management of recurrent ventricular tachyarrhythmias associated with Q-T prolongation

Eleven patients with acquired prolongation of the Q-Tc interval and recurrent ventricular tachyarrhythmias were studied. Five patients required 5 to 44 direct current shocks to correct prolonged ventricular tachyarrhythmias, and five were given at least two antiarrhythmic agents in an attempt to control the arrhythmias. In 4 of the 11 patients, when thioridazine, diuretic drugs and antiarrhythmic agents were withdrawn and hypokalemia or hypocalcemia corrected, ventricular tachyarrhythmias did not recur. The Q-Tc interval normalized in 2 to 3 days. Ventricular tachyarrhythmias were recurrent in the remaining seven patients, despite withdrawal of the drugs that caused the Q-Tc prolongation, attempted correction of hypokalemia when present and the administration of antiarrhythmic agents to four of the seven. All antiarrhythmic agents were then withdrawn in this group.

Immediately on the establishment of overdrive ventricular or atrioventricular sequential pacing in these patients, ventricular tachyarrhythmias were abolished. No breakthrough ventricular tachyarrhythmias occurred during temporary pacing. Temporary pacing was required for an average of 10 days and the Q-Tc interval normalized an average of 5 days from the onset of pacing. Three patients required a permanent pacemaker, one because of chronic complete heart block, one because of the sick sinus syndrome, and one because of frequent ventricular ectopic complexes complicating ischemic heart disease. All 11 patients survived their period of hospitalization.     

Expression of specific granule markers on the cell surface of neutrophil cytoplasts

The widespread assumption that cytoplasts generated from human polymorphonuclear leukocytes (PMNs) are vesicles consisting solely of cytoplasm surrounded by plasma membrane and devoid of granule activity remains to be tested. PMN cytoplasts were prepared by centrifugation of intact cells on a Ficoll step gradient in the presence of cytochalasin B. Two granule membrane markers, Mol, a fluorometrically detectable antigen, and cytochrome b, both of which have been shown to translocate to the plasma membrane during granule release, were compared for their activity in cytoplasts and intact PMNs. We found that the amount of Mol detected on the plasma membrane of intact PMNs, as compared with other membrane markers (such as antigens LFA-1 and beta 2m), increased 1.6- fold upon exposure of PMNs to Ficoll plus cytochalasin B prior to centrifugation. Another twofold increase in Mol expression occurred upon cytoplast preparation. Release of the granule enzymes, vitamin B12- binding protein, and lysozyme were also followed and correlated well (r = .78 and .92) with the amount of Mol antigen present on the cell surface. Cytochrome b was also found to be higher (1.4-fold) on plasma membranes isolated from cytoplasts than on plasma membranes isolated from intact control cells. These results indicate that some fusion of granule membranes and plasma membranes occurred during treatment of PMNs with Ficoll plus cytochalasin b and during cytoplast preparation.     

In vivo T‐cell depletion using alemtuzumab in family and unrelated donor transplantation for pediatric non‐malignant disease achieves engraftment with low incidence of graft vs. host disease

In vivo T‐cell depletion, using alemtuzumab therapy prior to SCT, can reduce the incidence of GVHD. This treatment has a potential to delay immune reconstitution resulting in increased morbidity due to viral illnesses. We retrospectively analyzed data on all pediatric patients with non‐malignant disorders who received alemtuzumab‐based conditioning regimens in our center over the last 10 yr (n = 91). Our data show an OS of 91.2%. The incidence of acute (grade 2–4) GVHD was 18.7% and that of chronic GVHD 5.5%. Viremia due to adenovirus, EBV and CMV was seen in 19.8%, 64.8% and 39.6% patients, respectively, with only two deaths attributed to viral infection (adenovirus). Chimerism level at three month was predictive of graft outcome. Nine patients, who had graft failure after first SCT, were salvaged with a second SCT using RIC and same donor (if available). Based on these results, we conclude that the use of in vivo T‐cell depletion is safe, achieves good chimerism and does not lead to increased morbidity and mortality due to viral infections. It is associated with a reduced incidence of chronic GVHD.     

Relationship of systolic BP to obstructive sleep apnea in patients with heart failure

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an independent risk factor for hypertension in the general population. Hypertension is, in turn, an important risk factor for the development and progression of congestive heart failure (CHF). Our objective was to determine whether OSA would be associated with elevated daytime BP in medically treated patients with CHF. DESIGN: Cross-sectional study. SETTING: Tertiary care, university-affiliated sleep disorders and heart failure clinics. PATIENTS: Three hundred one consecutive patients with CHF. MEASUREMENTS AND RESULTS: We measured daytime BP and performed overnight sleep studies to assess for the presence of OSA. Among these patients, OSA was present in 121 patients (40%) and their systolic BP was significantly higher than in patients without OSA. Patients with OSA were 2.89 times (95% confidence interval, 1.25 to 6.73) more likely to have systolic hypertension (ie, BP > or = 140 mm Hg) than those without OSA after controlling for other risk factors, including obesity. The degree of systolic BP elevation was directly related to the frequency of obstructive apneas and hypopneas. CONCLUSIONS: In medically treated patients with CHF, daytime systolic BP and the prevalence of systolic hypertension are significantly increased in patients with OSA, compared to those without OSA, independent of other potentially confounding factors. OSA may therefore have contributed to the presence of systolic hypertension in some of these patients.     

Children With Chronic Pain: Response Trajectories After Intensive Pain Rehabilitation Treatment

Intensive pain rehabilitation programs for children with chronic pain are effective for many patients. However, characteristics associated with treatment response have not been well documented. In this article we report trajectories of pain and functional impairment in patients with chronic pain up to 1 year after intensive pain rehabilitation and examine baseline factors associated with treatment response. Patients (n?=?253) with chronic pain and functional disability were assessed at 5 time points (admission, discharge, 1-month, 4-month, and 12-month follow-ups). Individual trajectories were empirically grouped using SAS PROC TRAJ. For functional disability, 2 groups emerged: treatment responders (88%) and nonresponders (12%). Using a binomial logistic regression model to predict disability trajectory group, no baseline variables were significant predictors for the disability trajectory group. For pain, 3 groups emerged: early treatment responders (35%), late treatment responders (38%), and nonresponders (27%). Using multinomial regression analyses to predict pain trajectory group, older age, higher pain scores, fewer social difficulties, higher anxiety levels, and lower readiness to change were characteristics that distinguished nonresponders from responders; no significant predictors distinguished the late responders from the early responders. These results provide key information on the baseline factors that influence intensive pain rehabilitation outcomes, including risk factors that predict treatment nonresponse. Our findings have implications for developing more targeted treatment interventions.

HIV Care Outcomes in Relation to Racial Redlining and Structural Factors Affecting Medical Care Access Among Black and White Persons with Diagnosed HIV—United States, 2017

AIDS and Behavior - Black/African American (Black) versus White persons are unequally burdened by human immunodeficiency virus (HIV) in the United States. Structural factors can influence social...     

Effect of cimetidine on serum gastrin and gastric emptying in man.

Paired studies of gastric emptying were performed in 10 healthy volunteers using a scintiscanning technique which provides information about the rate of emptying of both the liquid and solid components of a standard meal. Emptying rates of both components were not significantly different after oral administration of 400 mg cimetidine than after placebo. The increase in serum gastrin concentration produced by the meal was significantly greater after cimetidine than after placebo but there was no relationship between individual cimetidine-placebo differences in gastrin response and the corresponding cimetidine-placebo differences in rates of emptying. A positive correlation was demonstrated between the gastric emptying rate of the liquid component and the 1 h cimetidine absorption, indicating that normal individual variation in gastric emptying is probably responsible for much of the normal individual variation in the rate of cimetidine absorption.