Pulmonary presentations of amyloidosis.

Respiratory tract involvement with amyloid is rare. We report eight cases of lower respiratory tract amyloidosis including a case of isolated pulmonary interstitial amyloidosis treated with chemotherapy, two cases of recurrent endobronchial amyloid with airway obstruction successfully treated with laser therapy and three cases of localized nodular pulmonary amyloidosis. The subjects with endobronchial and nodular amyloid demonstrated good long-term survival, while those with systemic or interstitial pulmonary amyloid had progressive disease and poor survival. Circulating monoclonal immunoglobulins were identified in five of the eight cases as the likely cause of the amyloid.

Antioxidant enzyme activity in human abdominal aortic aneurysmal and occlusive disease.

The present study further investigates evidence for lipid peroxidation in atherosclerotic aortic tissue by determining the activity of antioxidant enzymes and concentrations of lipid peroxide fluorochromes in abdominal aortas from 15 patients with abdominal aortic aneurysms (AAA), an additional 7 patients with ruptured abdominal aneurysms, and 12 patients with atherosclerotic occlusive disease (AOD). Aortas from nonatherosclerotic organ donors served as nondiseased controls. Cu, Zn-superoxide dismutase (Cu,Zn-SOD) activities in AAA and AOD tissues were 16% and 25% of control activity, respectively. Mn-SOD activity in diseased aortae were about 65% of controls. CuZn-SOD protein in AAA and AOD was 56% and 100% of controls, respectively, resulting in significantly lower CuZn-SOD specific activity in these tissues. Ruptured AAA tissue also had low SOD activity and protein. Glutathione peroxidase (GPx) activity in AAA and AOD aortas was 70% and 65% of controls, respectively, and glutathione reductase (GR) activity in AAA and AOD aortas was 80% and 65% of control activities, respectively. These results were associated with significantly higher lipid peroxide fluorochromes, expressed as U/g aorta, in both groups of atherosclerotic aortas than in controls. AOD aortas had 33% higher fluorescence than AAA aortas, but the highest levels were seen in ruptured AAA. These data further support the involvement of free radicals and lipid peroxidation in atherosclerotic aortic disease, but do not indicate that these mechanisms are specifically involved in aneurysm formation versus development of occlusive disease.

Combination antiviral therapy controls severe post-liver transplant recurrence of hepatitis B virus infection.

The authors have successfully used combination ganciclovir and foscarnet chemotherapy to control viral replication following liver transplantation in a patient with severe recurrence of hepatitis B virus (HBV) infection. The disease was characterized by extremely high viraemias, deteriorating liver function, and high levels of intra-hepatic hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg). Treatment resulted in a greater than 30-fold reduction in serum HBV DNA and HBsAg levels. Liver function tests returned to normal and the histological progression of the disease was arrested. Hepatic cytoplasmic HBsAg decreased substantially but there was little change in HBcAg, implicating HBsAg rather than HBcAg in the liver injury. Combination antiviral chemotherapy using agents such as ganciclovir and foscarnet may offer a new approach to the management of post-transplant recurrence of HBV.

Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia.

In the human brain, receptor binding sites for angiotensin are found in the striatum and in the substantia nigra pars compacta overlying dopamine-containing cell bodies. In contrast, angiotensin-converting enzyme occurs in the substantia nigra pars reticulata and is enriched in the striosomes of the striatum. In this study, using quantitative in vitro autoradiography, we demonstrate decreased angiotensin receptor binding in the substantia nigra and striatum of postmortem brains from patients with Parkinson's disease. In the same brains the density of binding to angiotensin-converting enzyme shows no consistent change. We propose, from these results, that angiotensin receptors in the striatum are located presynaptically on dopaminergic terminals projecting from the substantia nigra. In contrast, the results support previous studies in rats demonstrating that angiotensin-converting enzyme is associated with striatal neurons projecting to the substantia nigra pars reticulata. These findings raise the possibility that newly emerging drugs that interact with the angiotensin system, particularly converting enzyme inhibitors and new nonpeptide angiotensin receptor blockers, may modulate the brain dopamine system.

Hepatitis due to nitrofurantoin.

OBJECTIVE: To report three cases of hepatitis related to the use of nitrofurantoin. CLINICAL FEATURES: Two patients who had been taking nitrofurantoin for several years, presented with severe liver failure. In both, the drug had been continued despite evidence of liver injury. A third patient presented with acute hepatitis after six weeks of nitrofurantoin therapy. INTERVENTION AND OUTCOME: One of the patients with liver failure died and the other underwent a successful liver transplantation. The third patient recovered after withdrawal of the drug. CONCLUSION: These cases emphasise the potential for serious hepatic reactions with nitrofurantoin, the danger of continuing the drug once liver damage has occurred and the need for careful monitoring of liver function during long-term therapy.

Amiodarone-associated phospholipidosis and fibrosis of the liver. Light, immunohistochemical, and electron microscopic studies.

The hepatic morphological findings in 3 patients treated with amiodarone, a potent and effective antiarrhythmic drug, are reported. An enlarged liver and mild elevation of hepatic enzymes were the most important clinical findings. Fibrosis, cholangitis, mixed inflammatory infiltrate, and cytoplasmic granularity of the hepatocytes were the main histologic changes common to all cases. In 2 of the cases the presence of Mallory bodies was confirmed by electron microscopy. In 1 of these 2 cases, Mallory bodies were also confirmed by immunostaining. Ultrastructurally, numerous cytoplasmic inclusions with a membranous or lamellar structure identical to those described in phospholipidosis were the most striking features seen in hepatocytes, biliary epithelial cells, Kupffer cells, and endothelial cells.