“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β₁-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with K_B's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (K_B = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β₁-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen.     

Use of human amniotic membrane in otolaryngologic practice

Human amnion is a readily available allograft with low antigenicity, high antimicrobial potential, and the ability to foster cpithelialization. We have used human amniotic membrane in our department for replacing nasal mucosa in Rendu-Osler-Weber disease, as tympanic membrane grafts, and for covering head and neck sites after flap necrosis. Our experience shows moderate success for management of severe epistaxis and excellent results in covering surfaces after flap necrosis. Use of amnion in eardrum perforations was unsuccessful and was discontinued. Properties of human amniotic membrane are listed and its application in the otolaryngologic practice is reviewed.     

The morphology of the QT interval predicts torsade de pointes during acquired bradyarrhythmias.

OBJECTIVES: The purpose of this study was to define the electrocardiographic (ECG) predictors of torsade de pointes (TdP) during acquired bradyarrhythmias. BACKGROUND: Complete atrioventricular block (CAVB) might lead to downregulation of potassium channels, QT interval prolongation, and TdP. Because potassium-channel malfunction causes characteristic T-wave abnormalities in the congenital long QT syndrome (LQTS), we reasoned that T-wave abnormalities like those described in the congenital LQTS would identify patients at risk for TdP during acquired bradyarrhythmias. METHODS: In a case-control study, we compared 30 cases of bradyarrhythmias complicated by TdP with 113 cases of uncomplicated bradyarrhythmias. On the basis of the criteria used for the congenital LQTS, T waves were defined as LQT1-like (long QT interval with broad T waves), LQT2-like (notched T waves), and LQT3-like (small and late) T waves. RESULTS: Neither the ventricular rate nor the QRS width at the time of worst bradyarrhythmia predicted the risk of TdP. However, the QT, corrected QT (QTc), and T(peak)-T(end) intervals correlated with the risk of TdP. The best single discriminator was a T(peak)-T(end) of 117 ms. LQT1-like and LQT3-like morphologies were rare during bradyarrhythmias. In contrast, LQT2-like "notched T waves" were observed in 55% of patients with TdP but in only 3% of patients with uncomplicated bradyarrhythmias (p < 0.001). A 2-step model based on QT duration and the presence of LQT2-like T waves identified patients at risk for TdP with a positive predictive value of 84%. CONCLUSIONS: Prolonged QT interval, QTc interval, and T(peak)-T(end) correlate with increased risk for TdP during acquired bradyarrhythmias, particularly when accompanied by LQT2-like notched T waves.     

Roles and indications for use of implantable defibrillator and resynchronization therapy in the prevention of sudden cardiac death in heart failure

Implantable devices are indicated in the primary and secondary prevention of potentially life-threatening ventricular tachyarrhythmias in patients with heart failure. Early studies, including the landmark MADIT trials, showed that implantable cardioverter–defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices can play a significant role in aborting and preventing ventricular arrhythmias, respectively, that can cause sudden cardiac death. To this day, there have been a number of randomized controlled trials, with respective substudy analyses, that have attempted to better understand the indications for these interventions in patient care. Here, we summarize the major results of these studies, and we discuss the role of ICD therapy for both ischemic and non-ischemic cardiomyopathy, emerging evidence in support of wearable defibrillators, and the impact of modified ICD programming strategies on patient outcomes. Regarding CRT therapy, the phenomenon of ventricular reverse remodeling is an important prognostic indicator in preventing future ventricular tachyarrhythmia episodes. In summation, we provide an overview of the possible selection criteria that can be used in identifying appropriate patients for ICD and/or CRT therapy, as supported by the data.     

The cost of home hospice care for terminal patients in Israel

This study examined and compared the cost of care provided to terminal metastatic cancer patients by home hospices and by conventional health services. The study population included 146 patients with metastatic cancer. Half received home hospice services, and the other half received conventional services. The average overall per-patient cost of care was, respectively, $4761 (operating costs included) and $12 434. On average, the costs were lower for older patients. A multiple regression analysis revealed that treatment units per patient, care framework, and patient age significantly contributed to explaining the cost variance. The findings suggest a financial advantage for home hospice care for terminal patients. This should be investigated further, as should the cost of informal caregivers and patient and caregiver satisfaction with the quality of care in both frameworks.