Jane T. Gaede

Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA‐binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

Case Report: Reversible Nefazodone-Induced Liver Failure

In a comprehensive review of data involving more than 3500 patients treated with nefazodone worldwide, no fatalities or cases of hepatitis or fulminant or subfulminant liver failure were reported (1). Nefazodone is a newer antidepressant that differs from selectively acting serotonergic agents used to treat depression. It inhibits synaptosomal uptake of serotonin and norepinephrine (2, 3). Because it has less anticholinergic, a1-adrenolytic, and antihistaminic activities than other agents, nefazodone is highly attractive for the treatment of depression due to its high safety profile. However, a recent report described three cases of fulminant liver failure attributed to the use of nefazodone (4). We report a case of severe hepatocellular jaundice that was successfully managed by withdrawal of nefazodone.

A fatal case of constructive pericarditis due to a marked, selective pericardial accumulation of amyloid

Distinguishing constrictive pericarditis from restrictive cardiomyopathy, usually due to amyloidosis, is a relatively frequent and difficult diagnostic problem. This report describes, for the first time, a patient with constrictive pericarditis caused by direct, extensive infiltration of the pericardium by amyloid, with only minimal amyloid in the myocardium, and a normal heart weight of 320 g. This patient demonstrates that amyloid may be predominantly deposited in the pericardium and actually cause constrictive pericarditis, as well as simulate its hemodynamic presentation by myocardial deposition. Given a clinical and hemodynamic presentation compatible with either constrictive or restrictive disease, an endomyocardial biopsy or other biopsy revealing amyloidosis does not necessarily rule out pericardial constriction that may be due to amyloid infiltration. The relationship between constrictive pericarditis, seen in this patient, and the other more common manifestations of amyloid heart disease, and the hemodynamic profiles of amyloid cardiomyopathy and constrictive pericarditis are reviewed.

Ulcer occurring in Zenker's diverticulum.

The radiographic and pathologic findings of a Zenkers-type diverticulum containing multiple ulcers are described. This rare complication probably represented peptic ulceration of the diverticular mucosa resulting from reflux of the gastric content.

Primary amyloidosis, pure red cell aplasia, and Kaposi's sarcoma in a single patient

A patient who developed primary amyloidosis, pure red cell aplasia, and Kaposis sarcoma is described. This is the second reported coincidence of Kaposis sarcoma and pure red cell aplasia and the first coincidence of Kaposis sarcoma and primary amyloid, thus enlarging the spectrum of plasma cell and immunoglobulin abnormalities seen in Kaposis sarcoma. Because immunelogic abnormalities have been described in all these diseases, it is felt that some primary immune dysfunction is the underlying cause of the three diseases in this patient.

Hemorrhagic adrenal adenoma simulating myelolipoma: Ct evaluation

We present a hemorrhagic adrenal adenoma surrounding and encompassing adjacent retroperitoneal fat to simulate the appearance of a myelolipoma by CT. A well-defined fibrous capsule, punctate calcification, and several macroscopic foci of fat within the mass led to an erroneous preoperative diagnosis. Lesions displaying large amounts of soft tissue attenuation material in addition to fat preclude a confident diagnosis of myelolipoma and should undergo directed percutaneous needle biopsy or surgery.

Death from renal cyst.

Simple renal retention cysts are the most common masses of the kidney, but rarely cause any clinical difficulty, are usually without attendant symptoms, generally posing only a differential diagnostic problem when discovered. However, renal cysts can predispose to hemorrhage, particularly in a setting of anticoagulation therapy. In this case, the patient died of massive hemorrhage from a small renal cyst while under anticoagulation treatment.

Serum enzyme alterations in hypothyroidism before and after treatment.

Recognition of a pattern of elevations in commonly measured serum enzymes [creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and glutamate oxalacetate transaminase (SGOT)] can facilitate the diagnosis of hypothyroidism, especially when muscle weakness is a symptom. Elevated levels of serum cholesterol, total protein, and albumin further contribute to a chemical profile of hypothyroidism, which can be observed in a routine chemistry screening test such as that obtained with the SMA 12/60 AutoAnalyzer. An illustrative case concerns a 50‐year‐old man who presented with angina pectoris and leg weakness. Subsequently he was found to have severe hypothyroidism. Special attention is given to the serum enzyme values which initially were elevated and fell to normal levels during thyroid replacement therapy. Isoenzyme fractionation of LDH and CPK indicated skeletal muscle as the source of the elevated enzyme activity. The literature on enzyme abnormalities in hypothyroidism is reviewed, with special reference to hypothyroid myopathy.

Myocarditis in Whipple's disease: An unsuspected cause of symptoms and sudden death

Whipples disease (WD) is an uncommonly diagnosed infection caused by the recently characterized bacillus, Tropheryma whippelii. The association of WD with pericarditis and endocarditis is widely recognized, although less attention has been paid to the myocardium as a site of disease. Although the disease was uniformly fatal before antibiotic therapy, current treatment usually results in cure. We report two patients whose deaths were directly related to cardiac involvement by WD and whose underlying disease escaped diagnosis for years. The first, a 60-year-old white woman, suffered a cardiovascular collapse, and lymphocytic myocarditis was demonstrated at autopsy. The second, a 48-year-old black man, had a lengthy history of progressive cardiac failure that terminated in arrhythmia. Extensive myocardial fibrosis, with lymphocytic and granulomatous inflammation, was demonstrated at autopsy. The presence of T. whippelii was confirmed by electron microscopic examination in both cases and by polymerase chain reaction in one. Patients with WD might harbor an undiagnosed lymphocytic or granulomatous myocarditis, and this diagnosis should be considered in the evaluation of cardiac failure.