Necrobiotic xanthogranuloma with paraproteinemia.

Necrobiotic xanthogranuloma with paraproteinemia is a distinct clinicopathologic entity defined by skin lesions that are characteristic both clinically and histologically, as well as a by variety of hematologic and chemical abnormalities. It is frequently associated with multiple myeloma or chronic lymphocytic leukemia. A patient with the characteristic findings but with an unusual course is described.

Chemical cholecystitis after intrahepatic chemotherapy. The case for prophylactic cholecystectomy during pump placement.

Recent repopularization of intrahepatic infusion chemotherapy has been made possible by the development of the implantable Infusaid pump. Surgical placement of a catheter into the gastroduodenal artery with division of collaterals to the stomach, duodenum, and pancreas has reduced the incidence of gastroduodenal ulceration and pancreatitis. The risk of chemical cholecystitis similarly demands prevention. Anatomically, the cystic artery is a branch of the right hepatic artery in over 95 percent of patients. As a result, even a normal gallbladder is subjected to high-dose chemotherapy with the risk of development of drug-induced cholecystitis. In our first six patients undergoing pump implantation who had normal appearing gallbladders at the time of surgery, two developed symptomatic cholecystitis, necessitating cholecystectomy after receiving intrahepatic chemotherapy. As a result, we recommend elective cholecystectomy at the time of arterial catheterization for intrahepatic chemotherapy.

Protamine-induced fatal anaphylaxis. Prevalence of antiprotamine immunoglobulin E antibody.

Protamine is used widely to reverse the anticoagulant effects of heparin and to delay the absorption of insulin. Although adverse reactions to protamine are reported infrequently and are usually mild, we recently observed the first fatal case of type I anaphylaxis resulting from protamine. This patient had previously been sensitized to protamine during cardiac catheterization and had high levels of protamine-specific immunoglobulin E in the serum. In a prospective study, we found that 10 of 19 diabetic patients (53%) who had received insulin containing insulin also had high levels of antiprotamine immunoglobulin E. In contrast, none of 27 nondiabetic healthy normal controls or 10 diabetics who had never received protamine or protamine-containing insulin had levels of antiprotamine immunoglobulin E over background. This study underscores the risks of routinely administering protamine to susceptible individuals and the need for alternative therapies.

Patterns of bone marrow involvement with small cell lung cancer.

The extent of tumor involvement, necrosis, reticulin, and megakaryocytosis were assessed in 25 patients with small cell lung cancer in their bone marrow at diagnosis. The pattern of marrow involvement was compared with clinical outcome and tolerance of therapy. Any marrow involvement, no matter how minor, is a poor prognostic factor. Neither more extensive involvement, nor greater marrow fibrosis significantly worsened the prognosis.

The effect of membrane-active agents on Sindbis virus morphogenesis.

In chicken cells infected by Sindbis virus and exposed to a variety of membrane-active compounds, virus release was inhibited. In infected cells exposed to antiserum directed against the virion glycoproteins E1 or E2, retinol, cortisone, Pb++ or insulin, the processing of two Sindbis virus precursor polypeptides which lead to the formation of virion polypeptides was inhibited. The B-protein, which is the precursor to both envelope proteins, accumulated in cells treated by these compounds. This precursor is generally not detected in chicken cells, presumably because it is processed rapidly. The cleavage of the precursor PE2 to the envelope glycoprotein E2 was also inhibited. E2 was also absent in cells exposed to menadione or to antiserum prepared against uninfected chicken cells. Since each of the compounds tested interfered with Sindbis virus polypeptide cleavage, despite their diverse mechanisms of action, it suggests that perturbation of normal membrane fluidity can interfere with Sindbis virus budding.

Interaction of Sindbis virus glycoproteins during morphogenesis.

In cells infected with the Sindbis temperature-sensitive mutants ts-23 and ts-10 (complementation group D), which contain a defect in the envelope glycoprotein E1, the precursor polypeptide PE2 is not cleaved to the envelope glycoprotein E2 at the nonpermissive temperature. This defect is phenotypically identical to the defect observed in the complementation group E mutant, ts-20. The lesion in ts-23 is reversible upon shift to permissive temperature, whereas that of ts-10 is not. Antiserum against whole virus, E1, or E2 also prevents the cleavage of PE2 in cells infected with wild-type Sindbis virus. Because the cleavage of PE2 is inhibited by the lesion in mutants that are genotypically distinct and by anti-E1 or -E2 serum, it appears that PE2 and E1 exist as a complex in the membrane of the infected cell.