Resident-to-resident aggression in long-term care facilities: insights from focus groups of nursing home residents and staff

OBJECTIVES: To more fully characterize the spectrum of resident‐to‐resident aggression (RRA). DESIGN: A focus group study of nursing home staff members and residents who could reliably self‐report. SETTING: A large, urban, long‐term care facility. PARTICIPANTS: Seven residents and 96 staff members from multiple clinical and nonclinical occupational groups. MEASUREMENTS: Sixteen focus groups were conducted. Content was analyzed using nVivo 7 software for qualitative data. RESULTS: Thirty‐five different types of physical, verbal, and sexual RRA were described, with screaming or yelling being the most common. Calling out and making noise were the most frequent of 29 antecedents identified as instigating episodes of RRA. RRA was most frequent in dining and residents' rooms, and in the afternoon, although it occurred regularly throughout the facility at all times. Although no proven strategies exist to manage RRA, staff described 25 self‐initiated techniques to address the problem. CONCLUSION: RRA is a ubiquitous phenomenon in nursing home settings, with important consequences for affected individuals and facilities. Further epidemiological research is necessary to more fully describe the phenomenon and identify risk factors and preventative strategies.     

Insulin receptor is an insulin-dependent tyrosine protein kinase: copurification of insulin-binding activity and protein kinase activity to homogeneity from human placenta.

The insulin-binding activity and insulin-dependent tyrosine protein kinase activity of the insulin receptor have been purified 2000-fold to homogeneity from human placental membranes. The purified receptor has one high-affinity binding site for insulin per mol of receptor. Its Vmax for phosphorylating angiotensin is 80 nmol of phosphate per min per mg of protein at 23 degrees C. The procedure used to purify the receptor includes chromatography on wheat germ agglutinin-agarose and on insulin-Sepharose. The purified receptor was eluted from insulin-Sepharose with 0.5 M NaCl and 1 mM dithiothreitol at pH 5.5. The addition of dithiothreitol was essential for recovery of the protein kinase. A silver-stained gel of the reduced purified receptor showed two major bands, Mr 95,000 (beta subunit) and Mr 135,000 (alpha subunit). The component of Mr 95,000 comigrated with the autophosphorylated beta subunit of the receptor. The latter was phosphorylated exclusively on tyrosine residues by an intramolecular process. In the presence of insulin, approximately 2 mol of phosphate was incorporated per mol of beta subunit. Two major beta subunit tryptic phosphopeptides were resolved by high-pressure liquid chromatography after autophosphorylation of the purified receptor in the presence or absence of insulin. It is concluded that the insulin binding and the insulin-dependent protein kinase are intrinsic components of the same oligomer since (i) they copurify to homogeneity, (ii) the purified receptor protein kinase is immunoprecipitated by polyclonal and monoclonal antibodies to the human insulin receptor, and (iii) phosphorylation of the beta subunit of the receptor occurs by an intramolecular reaction.     

Retrograde block during dual pathway atrioventricular nodal reentrant paroxysmal tachycardia

There are limited reported data regarding the occurrence of retrograde block during dual pathway atrioventricular (A-V) nodal reentrant paroxysmal tachycardia. This study describes two patients with this phenomenon. The first patient had 2:1 and type 1 retrograde ventriculoatrial block during the common variety of A-V nodal reentrance (slow pathway for anterograde and fast pathway for retrograde conduction). Fractionated atrial electrograms suggested that the site of block was within the atria. The second patient had type 1 retrograde block (between the A-V node and the low septal right atrium) during the unusual variety of A-V nodal reentrance (stow pathway for retrograde and fast pathway for anterograde conduction). The abolition of retrograde block by atropine suggested that the site of block was within A-V nodal tissue. Both cases demonstrate that intact retrograde conduction is not necessary for the continuation of A-V nodal reentrant paroxysymal tachycardia. Case 2 supports the hypothesis that the atria are not a requisite part of the A-V nodal reentrant pathway.     

Anti-aminoacyl tRNA synthetase immune responses: insights into the pathogenesis of the idiopathic inflammatory myopathies

PURPOSE OF REVIEW: One of the most striking humoral characteristics of the idiopathic inflammatory myopathies is the specific targeting of components of the translational machinery by the immune system. The most commonly targeted of these components are the aminoacyl tRNA synthetase (ARS) molecules. However, the relation between the immune responses to these molecules and the pathogenesis of the inflammatory myopathies remains obscure. This review will examine recent evidence that explores the links between the ARS molecules, inflammation, and apoptosis, with the aim of furthering our current understanding of the underlying pathogenesis of the myositis syndromes. RECENT FINDINGS: Several of the ARS molecules and their proteolytic fragments generated during inflammation and apoptosis have recently been shown to possess chemoattractant properties. The liberation of these fragments in the muscle microenvironment under certain circumstances may provide a proinflammatory context and lead to the influx of lymphocytes, macrophages, and specialized antigen-presenting cells to the site of muscle injury. The subsequent processing and presentation of these autoantigen fragments on major histocompatibility complex class I and II molecules may generate an ARS-specific autoimmune response, which may be responsible for amplification and propagation of muscle injury in these diseases. SUMMARY: The striking association between the inflammatory myopathies and anti-ARS antibodies implies a role for the ARS molecules in the pathogenesis of these syndromes. Recent data suggest that ARS molecules and their proteolytic fragments generated during the cell death process may be responsible for priming and sustaining a specific immune response in situ in myositis. How these molecules become altered and access the immune system in the disease microenvironment is an area of ongoing investigation.     

Low oral receptivity for dengue type 2 viruses of Aedes albopictus from Southeast Asia compared with that of Aedes aegypti

Dengue hemorrhagic fever has been a major health problem in Asia since the 1950s. During this period, the former principal vector of dengue viruses in Asia, Aedes albopictus, was replaced by Aedes aegypti in most major cities of the area. Ae. aegypti is now considered the main vector of dengue viruses in Asia. Surprisingly, however, this mosquito has been described as having a relatively low oral receptivity for dengue viruses compared with Ae. albopictus. In the present study, we compared the relative oral receptivities of Ae. aegypti and Ae. albopictus collected in southeast Asia from both sympatric and allopatric breeding sites. In all instances, the oral receptivity of Ae. aegypti to the dengue type 2 virus used was significantly higher than that of Ae. albopictus. We also compared the relative oral receptivity of Ae. aegypti and Ae. albopictus for two other low-passage strains of dengue 2. In all instances, Ae. aegypti was significantly more receptive than Ae. albopictus. It should be noted, however, that the difference was found only for Ae. albopictus recently collected from the field (Ta Promh strain, Cambodia, 2001) and not for an Ae. albopictus strain that had been colonized for many years (Oahu strain, Hawaii, 1971). We also observed a significant increase in the infection rate of Ae. albopictus of the Ta Promh strain with increasing generations in the laboratory. These observations demonstrate the importance of considering the colonization history of mosquitoes when assessing their susceptibility to infection with dengue viruses and, perhaps, other arboviruses.     

Electrophysiologic drug testing in prophylaxis of sporadic paroxysmal atrial fibrillation: Technique,application, and efficacy in severely symptomatic preexcitation patients

Electrophysiologic drug testing was performed in nine patients with severely symptomatic sporadic (2 to 13 [mean 4.2] attacks/24 months) paroxysmal atrial fibrillation (PAF). All patients had control inductions of sustained (> 30 seconds) AF by high right atrial stimulation, and attempted inductions following serial administration of drugs. Drugs tested were intravenous procainamide (1.0 to 1.5 gm) (five patients), intravenous propranolol (0.1 mg/kg) (three patients), oral quinidine (1.6 to 2.4 gm/day) (six patients), oral disopyramide (1.2 to 1.6 gm/day) (four patients), and oral aprindine (100 to 250 mg/day) (four patients). In all patients, one or more drugs prevented induction of sustained AF: procainamide (one patient), quinidine (five patients), disopyramide (four patients), and aprindine (four patients). All patients were treated with drugs which prevented induction of sustained AF and followed for 8 to 40 (mean 24) months. Seven patients tolerated their drugs: six had no AF and one had several short nonsustained attacks. Two patients did not tolerate their drugs: one had paroxysmal palpitation (on decreased aprindine dosage), and one had AF (while off of aprindine). In conclusion, electrophysiologic drug testing is feasible in patients with sporadic PAF. Inability to induce sustained AF following drug administration suggests successful prophylaxis of spontaneous PAF with the same drug.     

Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

Background.

Vascular endothelial growth factor and platelet-derived growth factor signaling in the tumor microenvironment appear to cooperate in promoting tumor angiogenesis.

Patients and Methods.

We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks.

Results.

A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks could be safely combined with imatinib 800 mg daily. Common toxicities included fatigue, nausea, vomiting, edema, proteinuria, and anemia, but were not commonly severe. A total of 23 patients with metastatic melanoma (48% with American Joint Commission on Cancer stage M1c; median age, 63 years) were enrolled in the first stage of phase II. The 16-week progression-free survival rate was 35%, leading to termination of phase II after the first stage. In the small subset of patients who remained on study with lesions evaluable by DCE-MRI, significant decreases in tumor vascular permeability were noted, despite early disease progression using the Response Evaluation Criteria In Solid Tumors.

Conclusion.

Bevacizumab and imatinib can be safely combined at the maximum doses used for each agent. We did not observe significant clinical activity with this regimen in melanoma patients.

Implications for Practice:

Vascular endothelial growth factor (VEGF)-targeted antiangiogenic therapy has proven clinical efficacy as a standalone therapy in renal cell carcinoma and glioblastoma multiforme. Also, enhancement of conventional cytotoxic chemotherapy efficacy has been observed in colorectal, non-small-cell lung, breast, and ovarian cancers. Optimal strategies to cotarget angiogenic cytokines combined with VEGF have not been defined. It was found that bevacizumab could be safely combined with imatinib, which was used as a platelet-derived growth factor receptor inhibitor in our study. High-dose imatinib-related edema was not observed when paired with bevacizumab. This regimen might be suitable for further investigation in other cancers but apparently not in melanoma.