Benign lymphocytic angiitis and granulomatosis: experience with three cases

Of three patients with lung-biopsy-proven benign lymphocytic angiitis and granulomatosis, two experienced complete resolution of their disease from therapy with chlorambucil and one underwent spontaneous remission with no drug therapy after lung biopsy and removal of a benign spindle cell thymoma. Clinically, it is difficult to determine whether benign lymphocytic angiitis is a low-grade (prelymphomatous) lymphoma or a vasculitis. Its position in this spectrum of diseases is uncertain. Nonetheless, benign lymphocytic angiitis and granulomatosis corresponding to a low-grade angiocentric immunoproliferative lesion is a clinicopathologically useful concept.     

Hamman-Rich syndrome revisited

In this article, we retrospectively review 29 cases of Hamman-Rich syndrome. As in some other recent reports, we have used the term "acute interstitial pneumonia" to emphasize the clinical and pathologic features of these cases and to distinguish them from the more common chronic interstitial pneumonias, particularly idiopathic pulmonary fibrosis. Of the 29 patients, 12 survived, some after a long and complicated hospitalization. The histologic features were those of organizing diffuse alveolar damage, and some patients, including survivors, had extensive fibroblastic distortion of lung parenchyma. The overall survival among these patients was not appreciably different from the survival of patients with the adult respiratory distress syndrome in general.     

Right atrial emptying fraction non-invasively predicts mortality in pulmonary hypertension

Right-sided heart failure is the most common cause of death in pulmonary hypertension (PH). Echocardiographic measurements of right atrial (RA) size are associated with worse outcome in PH, however the association between RA function and death in PH has not been well-described. 160 PH patients (World Health Organization groups 1–5) underwent cardiac magnetic resonance imaging (cMRI) and right heart catheterization (RHC) within 6 weeks of each other at a tertiary care academic medical center in the United States. We measured cMRI RA maximum and minimum volumes indexed to body surface area and calculated RA emptying fraction (RAEF). We evaluated the relationship between RAEF and clinical variables with death using Cox proportional hazard models. 57 deaths occurred during a median follow-up of 3.5 years (36?% died overall, 10?% per year). RAEF was directly correlated in univariate analyses with right ventricular (RV) ejection fraction, left ventricular (LV) ejection fraction, LV size, cardiac index, absence of tricuspid and pulmonic regurgitation, absence of pericardial effusion, estimated glomerular filtration rate, 6-minute walk distance, and pulmonary arterial oxygen saturation, whereas it was inversely correlated with death, BNP, heart rate, mean RA pressure, mean PA pressure, pulmonary and systemic vascular resistance, RV size, and RA size. Using multivariate analyses, RAEF had a robust inverse association with death after adjusting for measured risk factors (HR per 5?% change in RAEF: 0.83 [95?% CI 0.73–0.94], p?=?0.003). In PH patients, decreased RAEF by cMRI is independently associated with worse survival after adjustment for other risk factors.     

Metabolism of spironolactone by adrenocortical and hepatic microsomes: relationship to cytochrome P-450 destruction

Previous investigations have established that spironolactone (SL) is converted to a reactive metabolite by adrenocortical NADPH-dependent enzymes, resulting in the destruction of microsomal cytochrome(s) P-450 and decreases in steroid hydroxylase activities. Hepatic microsomes, by contrast, do not activate SL. Studies were done to characterize the activation pathway by comparing adrenal with hepatic metabolism of SL in guinea pigs. In the absence of NADPH, both adrenal and hepatic microsomal preparations converted SL to its deacetylated metabolite, 7 alpha-thio-SL. NADPH had no effect on hepatic SL metabolism but stimulated adrenal metabolism of SL. In the presence of NADPH, very little 7 alpha-thio-SL was recovered from the adrenal incubations, suggesting that the 7 alpha-thio-SL was further metabolized by NADPH-dependent enzymes. The latter hypothesis was confirmed by incubating microsomal preparations with 7 alpha-thio-SL as the substrate. In the presence of NADPH, 7 alpha-thio-SL was rapidly metabolized by adrenal microsomes but was not metabolized by hepatic preparations. Under the same incubation conditions, 7 alpha-thio-SL promoted the destruction of adrenal cytochrome(s) P-450 but had no effect on hepatic monooxygenases. 7 alpha-Thio-SL was far more potent than SL in promoting the destruction of cytochrome(s) P-450, suggesting that the metabolite might be an intermediate in the actions of the parent compound. Indeed, inhibition of SL conversion to 7 alpha-thio-SL by the esterase inhibitor, diethyl p-nitrophenyl phosphate blocked the effects of SL on adrenal cytochrome(s) P-450. Diethyl p-nitrophenyl phosphate did not affect the actions of 7 alpha-thio-SL on cytochrome(s) P-450.(ABSTRACT TRUNCATED AT 250 WORDS)