Adenosine A1 Antagonism Attenuates β-adrenergic–resistant Sudden Hypoxic Cardiac Insufficiency

Objectives: In states such as hypoxia, shock, and cardiac arrest, compromised systemic oxygenation or perfusion appears to induce cardiac insufficiency that can be resistant to β‐adrenergic drugs. Elevated levels of adenosine may mediate such β‐adrenergic–resistant cardiac insufficiency via the adenosine A₁ receptor (A₁AdoR). The objective of this study was to test the hypothesis that selective A₁AdoR antagonism attenuates hypoxic cardiac insufficiency more efficaciously than β₁‐adrenergic agonism or nonselective adenosine antagonism. Methods: Rats were paralyzed and ventilated to a pCO₂ level of 35–40 mm Hg. Ten minutes before hypoxia (inspired O₂ concentration = 5%), rats were treated intravenously with one of the following: 0.1 mg/kg BG‐9719 (n= 9), 10 mg/kg NPC‐205 (n= 10; BG‐9719 and NPC‐205 are selective A₁AdoR antagonists, with durations of action of 30–60 minutes and 60–90 minutes, respectively), 10 mg/kg aminophylline (n= 12), 5 μg/kg/min dobutamine (n= 11), or control solutions. These drug doses maximized survival duration in dose‐response studies. Results: Before hypoxia, cardiac work was increased more by aminophylline and dobutamine than by BG‐9719. Mean (±SEM) duration of survival (in minutes) after hypoxia increased from <13 (control solutions) to 13.8 (±1.4) (dobutamine), 20.0 (±1.6) (aminophylline), 31.7 (±4.6) (BG‐9719), and 40.5 (±7.5) (NPC‐205) (p < 0.0001). Heart rate and dP/dt decreased rapidly after hypoxia, but decreases were attenuated with BG‐9719 and NPC‐205 compared with dobutamine (p < 0.05) and tended toward attenuation with aminophylline. Conclusions: BG‐9719 and NPC‐205 improved survival duration, heart rate, and left ventricular contractility during hypoxia more efficaciously than dobutamine and possibly aminophylline. Selective A₁AdoR antagonists warrant further study as alternatives to β‐adrenergic agonists in hypoxia, shock, and cardiac arrest, in which compromised systemic perfusion or oxygenation impairs cardiac output.     

Comparison of Sonography and Magnetic Resonance Imaging for Spring Ligament Abnormalities

Objective. The purpose of this study was to determine whether sonography is as accurate as magnetic resonance (MR) imaging for depicting abnormalities of the spring ligament in patients with symptomatic posterior tibial tendon (PTT) dysfunction. Methods. Sixteen patients (18 ligaments) with symptomatic PTT dysfunction were prospectively evaluated with sonography and MR imaging. Results. Magnetic resonance imaging showed spring ligament tears in 8 of 18 feet, including 6 incomplete tears and 2 complete tears. Sonography showed spring ligament tears in 7 of 18 feet, including 6 incomplete tears and 1 complete tear. The findings of sonography and MR imaging were concordant in 17 of 18 feet (94%). Six of the 8 spring ligament tears on MR imaging were associated with posterior tibial tendinosis or tears. Conclusions. Sonography is an effective imaging option in assessing spring ligament abnormalities in patients with symptomatic PTT dysfunction.     

INTRALESIONAL VINBLASTINE IN THE TREATMENT OF ORAL KAPOSI'S SARCOMA

Kaposi's sarcoma is a common tumour in HIV-infected patients, frequently involving the oropharynx. Conventional treatment with radiotherapy is efficacious, but causes considerable discomfort. This paper illustrates a new technique of local injection of vinblastine into oral lesions, which combines satisfactory palliation with high patient acceptability.     

Most patients are eligible for an alternative to conventional whole breast irradiation for early‐stage breast cancer: A National Cancer Database Analysis

We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast‐conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I‐III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET‐alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET‐alone based on the CALGB 9343/PRIME‐II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC‐ESTRO trial/ASTRO guidelines/ABS guidelines/GEC‐ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET‐alone. This analysis shows that a large proportion of patients with node‐negative breast cancer are eligible for HFRT, APBI and/or ET‐alone after breast‐conserving surgery.     

Adjuvant continuous metronomic adriamycin + cyclophosphamide followed by weekly nab‐paclitaxel for high‐risk early‐stage breast cancer

Many studies have sought to optimize the dosing schedule of adjuvant chemotherapy in early‐stage breast cancer. Here, we assessed the use of continuous metronomic weekly doxorubicin plus daily oral cyclophosphamide (AC) with continuous G‐CSF growth factor support for 12 weeks followed by weekly nab‐paclitaxel (nP) for 12 weeks. A nonrandomized phase II clinical trial was designed to assess (1) DFS at 2 years, (2) dose delivered, (3) use of nP in the adjuvant setting, and (4) toxicities. The dosing of A was 24 mg/m2 IV weekly and C was 60 mg/m2 oral daily (with scheduled filgrastim 5mcg/kg 6 days/week); nP, 100 mg/m2 IV weekly. For patients with HER2 + disease, trastuzumab was started during the nP portion of therapy and continued for 12 months. Sixty patients enrolled with a median follow‐up of 6 years. Node‐positive disease was present in 58% of patients. Receptor categories included hormone receptor positive/HER2 negative (n = 25; 42%); triple negative (n = 19; 32%); or HER2 positive (n = 16; 27%). DFS at 2 years was 93%. Mean dose delivered was greater than 90% for metronomic AC and 88% for nP. Treatment was well tolerated with a 2% incidence of febrile neutropenia. Continuous metronomic AC followed by nP was well tolerated in our patients with comparable DFS to historical controls.     

Cervical zygapophyseal joints: geometrical parameters and relationship to cervical kinematics

The relationship was examined between the height and slope of the cervical zygapophyseal joints and the patterns of motion of the cervical vertebrae. The height and orientation of the C₃---C₇ superior articular processes were measured in lateral radiographs of 40 normal subjects. The C₄-C₆ facets were oriented at approximately 40° to the vertical, while the C₃ and C₇ facets were more steeply oriented. The heights of the superior articular processes were found to increase at progressively lower vertebral levels. Contrary to published views, the slope of the superior articular facets has no bearing on the pattern of motion of the cervical vertebrae. No relationship was found between slope of the facets and the location of the instantaneous axes of rotation of the cervical vertebrae. In contrast the height of the articular processes was perfectly related to the location of the axes of rotation. Articular height, but not slope, is a major determinant of the patterns of motions of the cervical vertebrae.

This study provides data necessary to confirm or deny the putative roles of the cervical zygapophyseal joints in determining motion of the cervical spine in the sagittal plane.