Serial lung function testing in patients treated with amiodarone: a prospective study

PURPOSE: Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent. PATIENTS AND METHODS: Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days. RESULTS: For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent. CONCLUSION: An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity.     

Median frequency--a new parameter for predicting defibrillation success rate

STUDY HYPOTHESIS: Current American Heart Association guidelines recommend immediate defibrillation of ventricular fibrillation. When this is unsuccessful, there are no guidelines to help determine the optimum time at which to defibrillate after the administration of an alpha-adrenergic agonist. Previous studies have shown that the median frequency of the ventricular fibrillation ECG signal correlates with myocardial perfusion during CPR. We hypothesized that median frequency could predict the success of defibrillation and thus accurately determine the most appropriate time at which to defibrillate during ventricular fibrillation. STUDY POPULATION: Twenty-two mixed-breed swine weighing more than 15 kg were studied. METHODS: Ventricular fibrillation was induced electrically, and the ventricular fibrillation ECG signal was analyzed using fast Fourier analysis. After ten minutes of ventricular fibrillation, mechanical CPR was begun. After three minutes of CPR, the animals received one of three alpha-adrenergic agonists and CPR was continued. Defibrillation was attempted three and one-half minutes after drug administration. The average median frequency 20 seconds before defibrillation was calculated. Sensitivity and specificity of median frequency with respect to defibrillation success were determined. RESULTS: A median frequency of 9.14 Hz had a sensitivity of 100% and a specificity of 92.31% in predicting the results of defibrillation in this model. CONCLUSION: The median frequency may serve as a valuable parameter to guide defibrillation therapy during ventricular fibrillation.     

Rapid Increase in Marrow Fat Content and Decrease in Marrow Perfusion in Lumbar Vertebra Following Bilateral Oophorectomy: An MR Imaging-Based Prospective Longitudinal Study

ObjectiveBilateral oophorectomy leads to reduced bone mineral density (BMD), and reduced BMD is associated with increased marrow fat and reduced marrow perfusion. Purpose of this study was to investigate how soon these changes occur following surgical oophorectomy.ResultsReduced BMD, increased marrow FF, and reduced marrow perfusion occurred synchronously post-oophorectomy. There was a sharp decrease of 12.5 ± 7.2% in BMD (n = 6), a sharp increase of 92.2 ± 46.3% (n = 6) in FF, a sharp decrease of 23.6 ± 3.9% in maximum contrast enhancement (n = 5), and of 45.4 ± 7.7% for enhancement slope (n = 5) during the initial 3 months post surgery. BMD and marrow perfusion continued to decrease, and marrow FF continued to increase at a slower rate during the following 18 months. Friedman test showed a significant trend for these changes (p < 0.05).ConclusionBilateral oophorectomy leads to a rapid decrease in lumbar BMD, an increase in marrow fat content, and a decrease in marrow blood perfusion.     

Experimental herpes simplex virus encephalitis: Comparative effects of treatment with cytosine arabinoside and adenine arabinoside.

Experimental herpesvirus encephalitis in weanling mice was treated with either cytosine arabinoside or adenine arabinoside to determine the comparative effectiveness of the two compounds on survival and on the concentration of virus in the brain. The uniformly fatal course of the encephalitis was not altered by any dosage of cytosine arabinoside. In contrast, treatment with adenine arabinoside resulted in long-term survival of the majority of the infected animals. The concentration of virus measured in the brains of animals treated with two different dosages of cytosine arabinoside indicated initial suppression of viral replication with a subsequent rise to levels higher than those in the untreated controls. In the brains of adenine arabinoside-treated animals, titers of virus gradually diminished to undetectable levels by the eighth day after institution of therapy.     

A Rare Case of Carcinoma Cuniculatum Involving the Larynx in Association with a Saccular Cyst

Carcinoma cuniculatum (CC), a rare, well-differentiated variant of squamous cell carcinoma, is uncommon in head and neck sites but when it does occur is most common in the oral cavity. Here we report a rare case of CC involving the larynx. A 49-year-old man presented with 10 months of worsening hoarseness and, despite multiple biopsies, no diagnosis of malignancy could be established. Eventual partial excision of the lesion and histologic review of prior specimens confirmed the diagnosis of CC. Focally, a transition to respiratory epithelium indicated the presence of an associated saccular cyst. Total laryngectomy was performed and 6 months later the patient is free of disease. Only two prior cases of CC have been reported in the larynx. Diagnosis of CC is challenging given the low grade histologic features and awareness of this entity for both treating physicians and the pathologist is important to reach a diagnosis of malignancy. This case highlights the challenges in diagnosis of CC, especially in unusual locations and when associated with other lesions such as a saccular cyst. Awareness of this rare tumor type combined with close communication between treating clinicians, radiologists and pathologists should allow earlier diagnosis and treatment.     

Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

Background

Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma.

Questions/purposes

We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material.

Methods

We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale.

Results

Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements.

Conclusions

These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation.

Clinical Relevance

By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.