Faculty Bibliography

Five male homosexuals, four of whom had Kaposi's sarcoma, presented with painful swelling of the lower extremity. The overlying skin was erythematous and exquisitely tender. Deep vein thrombosis was strongly suspected in all patients. Venography, however, revealed no evidence of venous occlusion. This condition, which in this report is termed the hyperalgesic pseudothrombophlebitis syndrome, appears to be another unusual manifestation of the acquired immune deficiency syndrome. It should be considered among the entities known to mimic deep vein thrombosis and must be recognized in order to prevent unnecessary anticoagulation in these patients.

Episodes of fever, serositis, and arthritis in familial Mediterranean fever (FMF) suggested circulating mediators of acute inflammation (e.g., neutrophil activation). The mean serum neutrophil-aggregating activity of 51 FMF patients was 2.5 +/- 0.2 cm2/min, compared to 1.0 +/- 0.1 cm2/min in 20 normal controls (P less than 0.0002). Lipid extracts of FMF sera retained neutrophil-aggregating activity and had UV absorbance peaks at 269 and 279 nm, indicating the presence of lipids with a conjugated triene structure. Chromatography of extracts yielded peaks that were coeluted with reference dihydroxyicosatetraenoic acids, had UV absorbance peaks at 259, 269, and 279 nm, and possessed neutrophil-aggregating activity. The presence of leukotriene B4 was excluded by chromatography following methyl-esterification. Monohydroxy compounds identified in FMF extracts by gas chromatography/mass spectrometry included 5-hydroxyicosatetraenoic acid, and 9- and 13-hydroxyoctadecadienoic acids. Hydroxy acids were present in 19 of 31 FMF sera and absent in extracts of sera from 8 patients with active systemic lupus erythematosus, 7 with fever from infection, and 12 normal controls. The finding of circulating mono- and dihydroxy fatty acids in FMF suggests that defects in the formation or elimination of these compounds might play a role in the pathogenesis of FMF.

The influence of a variety of clinical and biochemical parameters on the activities in serum of ribonuclease (RNAse) selective for polycytidylic acid (RNAse C) were examined in 90 adult patients with cancer. The clinical data base determined on each patient included: RNAse C level, carcinoembryonic antigen (CEA) level, age, sex, race, presence (or absence of metastases, type of cancer, site of metastasis, renal function blood urea nitrogen [BUN], creatinine), hepatic function (bilirubin, alkaline phosphatase), and nutritional status (percent ideal body weight, percent weight loss, and albumin). Common tumor types studied included: colon (21), lung (18), breast (15), and hepatocellular carcinoma (10). For comparison, 175 nonmalignant control patients were studied to establish the normal range for RNAse. In patients with cancer, RNAse levels were increased in 57% and CEA levels were above 10 ng/dl in 36%. Although patients with BUN greater than 25 mg/dl or creatinine greater than 1.5 mg/dl were not entered on the study, nonetheless, RNAse was significantly (P less than 0.05) associated with both BUN and creatinine. Nutritional status also had an important influence on RNAse levels as both percent weight loss and percent ideal body weight were significantly (P less than 0.05) associated with circulatory RNAse: weight loss resulted in higher RNAse levels. These results account in part for the increased RNAse levels seen in those malignant conditions such as pancreatic and lung cancer commonly associated with weight loss in advanced stage. The possibility that circulatory RNAse C determination will provide a sensitive means for assessing nutritional status in cancer patients will require prospective evaluation.

Although pancreatic enzymes clearly degrade R binder, a nonintrinsic factor binder, the full scope of the pancreatic role in cobalamin absorption remains the subject of debate. Therefore the direct effect of pure human pancreatic juice (PPJ) on ileal cobalamin absorption in the absence of intrinsic factor was studied. PPJ significantly enhanced cobalamin uptake in guinea pig ileal loop perfused in vivo. It did not do so in the jejunum. This PPJ activity in the ileum was further stimulated by enteropeptidase and inhibited by aprotinin. The intestinal mucosa remained intact during our study by morphologic and inulin clearance criteria and behaved normally with respect to intrinsic factor and nonintrinsic factor binders. Since no intrinsic factor was present in the perfusate, PPJ must directly enhance cobalamin uptake by the ileum, perhaps promoting cobalamin attachment to receptor sites for subsequent transport by intrinsic factor. PPJ thus seems to affect cobalamin absorption at several levels. Previous studies have established its interaction with luminal R binders and with bile. The findings now indicate that pancreatic juice may have an additional, more direct role in promoting cobalamin absorption in the ileum.

Non-endemic Salmonella bacteremia tends to occur in patients with chronic disease. We reviewed all cases of Salmonella infection documented in adults at Bellevue Hospital during the years 1975-1982. Unexpectedly, the most frequent underlying disease found among bacteremic patients was systemic lupus erythematosus (SLE). Patients with SLE accounted for 6 of 30 Salmonella bacteremias as compared with 13 of 2,388 non-Salmonella gram-negative bacteremias. Salmonella was the single most frequent gram-negative isolate from the blood of SLE patients. All lupus patients with Salmonella infection were bacteremic. In contrast, isolates from blood represented only 23% of all Salmonella infections documented in the non-lupus population. Presentation was characterized by fever (greater than 103 degrees F) and abdominal pain. Four of the 6 patients were hypocomplementemic. All were receiving immunosuppressive therapy. We conclude that SLE patients in a municipal hospital setting are at increased risk for Salmonella sepsis. This should be considered when empiric antibiotic therapy is initiated.

Nonsteroidal anti-inflammatory drugs are thought to prevent inflammation in rheumatoid arthritis by inhibiting prostaglandin synthesis. This observation does not explain, however, why nonsteroidal anti-inflammatory drugs are able to control inflammation caused by other mediators. To determine whether nonsteroidal anti-inflammatory drugs also exert an effect on neutrophil activation, in vitro and in vivo studies were undertaken. Aggregation, superoxide anion generation, and lysosomal enzyme release were assessed. The nonsteroidal anti-inflammatory drugs were found to inhibit these neutrophil responses, but the patterns of inhibition varied from drug to drug. These findings suggest that nonsteroidal anti-inflammatory drugs may have direct effects on neutrophil activation that are independent of their shared inhibition of prostaglandin synthesis

Organ cultures of choroid plexus tissues from the lateral ventricle of juvenile rats have been maintained for periods up to 7 wk in a chemically defined, serum-free media. Of several media and various supplements evaluated, the best growth and survival was obtained with the Pasadena Foundation for Medical Research-4 media supplemented with three hormones: epidermal growth factor, insulin, and hydrocortisone. Autoradiographic studies demonstrated that the epithelial cells incorporated [3H]leucine and [3H]thymidine indicating active protein and DNA synthesis, respectively. The organ cultures were characterized by bulbous, vesicular outgrowths from the choroidal villi explants. The fluid-filled lumina of the vesicles reached diameters of 900 microns and were easily accessed by micropipettes. The walls of the vesicles were composed of single layers of epithelial cells in which the ultrastructural features in the in vivo tissue were well maintained. The in vivo polarity (apical end toward the media and basilar end of the cells toward the luminal cavity) was also maintained. This morphologically stable in vitro system seems to be a promising model for investigation of secretory mechanisms of choroidal tissue.

Activated complement components and immune complexes cause neutrophil aggregation in vitro and in vivo. We have previously demonstrated that sera of patients with active systemic lupus erythematosus (SLE) provoke the aggregation of normal neutrophils in vitro. In this study the serum or plasma of 4 such patients was fractionated on Sephadex G-75. In 3 patients neutrophil aggregating activity (NAA) was detectable in fractions which coeluted with reference C5-derived peptides (estimated molecular radius of 17,000). The activity of these fractions was inhibitable by antibodies to human C5. All patients also had activity that coeluted with reference immune complexes. In addition, material of apparent molecular radius under 12,000 that contributed to the neutrophil aggregating activity of SLE sera was detected. In separate experiments increased levels of C5a desarg were demonstrated during active disease by means of radioimmunoassay. These findings suggest that multiple neutrophil aggregants circulate during the course of active SLE. The formation of intravascular leukoaggregates may contribute to endothelial injury in this disease.