Recurrent stent thrombosis associated with lupus anticoagulant due to renal cell carcinoma

A case is presented of recurrent stent thrombosis unexplained by angiographic appearance, which subsequently revealed a diagnosis of antiphospholipid syndrome secondary to renal cell carcinoma.     

Localization and quantitation of the vitamin D binding protein (Gc- globulin) in human neutrophils

Plasma-derived vitamin D binding protein (DBP) is an important physiologic regulator of the neutrophil chemotactic response to activated complement. A cell-associated form of DBP has been observed in numerous cell types. We now report that mature, circulating human neutrophils also contain cell-associated DBP. Immunofluorescence studies of normal untreated neutrophils showed the presence of DBP on the cell surface. Western blotting of detergent-soluble neutrophil lysates with a polyclonal anti-DBP showed two major immunoreactive bands, one with an apparent molecular weight of 56 Kd (identical to purified plasma-derived DBP) and a second less prominent band at 12 to 14 Kd. Quantitation of the immunoreactive bands by video densitometry indicated that normal human neutrophils contain 1.5 +/- 0.8 ng DBP/10(6) cells (n = 9). Immunoprecipitation of detergent-soluble lysates with the polyclonal anti-DBP showed only the 56-Kd form by Western blotting. In contrast, a monoclonal anti-DBP immunoprecipitated the 12 to 14 Kd form of DBP from lysates of surface-radioiodinated cells. Western blots of subcellular fractions showed that immunoreactive bands were found in the specific (secondary) granule and plasma-membrane fractions. In addition, pretreatment of neutrophils with 10 nmol/L phorbol myristate acetate (PMA) resulted in approximately a 50% reduction in the amount of DBP in both the specific granule and plasma-membrane fractions. Finally, analysis of the cell- free supernates showed that DBP was spontaneously released into the extracellular milieu: moreover, this release was enhanced if the cells were first stimulated with C5a, formyl-norleucyl-leucyl-phenylalanine (fNLP) or PMA.     

Depressed functional and phenotypic properties of T but not B lymphocytes in idiopathic thrombocytopenic purpura

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which the abnormality in cellular immunity has remained only vaguely defined. Previously we have shown that patients with ITP in its active phase have abnormal T cell subsets. We then examined the phenotypes of T and B lymphocytes in an additional 28 patients with ITP and 32 age- and sex-matched normal controls and compared the lymphocytes' capacity to respond to polyclonal T, T cell-dependent B, and B cell mitogens. Blastogenesis to optimal (5.0 micrograms/mL) and suboptimal (0.5 microgram/mL) concentrations of the polyclonal T cell mitogens were markedly depressed in patients compared with normal controls (P less than .0005). Similarly, a severe depression in response was noted with the polyclonal T cell-dependent B cell mitogen (P less than .000001). No difference was seen, however, with the polyclonal B cell mitogen. The proportions of pan-T and T helper/inducer lymphocytes were significantly depressed (P less than .005 and P less than .000005 respectively), and the T suppressor/cytotoxic lymphocytes increased (P less than .02) in patients relative to controls. But there was no difference in the proportion of B lymphocytes or in their functional response. The abnormal cellular immunity appears to be due to a defect in the T lymphocyte population without involvement of the B lymphocytes.     

Predictors of Positive Head-Up Tilt Test in Patients with Suspected Neurocardiogenic Syncope or Presyncope

OH, J.H., et al .: Predictors of Positive Head-Up Tilt Test in Patients with Suspected Neurocardiogenic Syncope or Presyncope. Neurocardiogenic syncope is the most common cause of syncope in patients who present in outpatient clinics. Head-up tilt test (HUT) has been widely used to diagnose neurocardiogenic syncope. However, the HUT does not always produce a positive response in patients with suspected neurocardiogenic syncope. The aim of the present study was to assess the clinical history and characteristics of patients with suspected neurocardiogenic syncope or presyncope who undertook HUT, and to identify prognostic factors of a positive HUT response. During the first phase of HUT, patients were tilted to a 70-degree angle for 30 minutes. If the first phase produced a negative response, the second phase was subsequently performed involving intravenous isoproterenol administration. Of 711 patients, 423 (59.5%) patients showed a positive HUT response. In contrast to previous studies, this study showed that the vasodepressive type (76.6%) was the most common pattern of positive response, and that the rate of positive response during the first phase was low (7.1%). By multivariate analysis, the occurrence of junctional rhythm was found to be a predictor of an impending positive response in HUT   (P < 0.001)   . The shorter time interval between the last episode and HUT was also a predictor of positive response   (P = 0.0015)   . Younger age   (P = 0.0003)   and a history of physical injury during a syncopal episode   (P = 0.019)   were found to be associated with a positive response in the first phase of HUT. (PACE 2003; 26[Pt. I]:593–598)     

Balancing pain and analgesic treatment in the home-dwelling elderly

BACKGROUND: In elderly persons, pain is a common problem, and analgesic medicines are among the most frequently used drugs. OBJECTIVE: To describe the use of analgesic medication and its relation to daily pain and morbidity in home-dwelling elderly people aged at least 75 years. METHODS: A random sample of 700 subjects aged at least 75 years was drawn from the total population of Kuopio, Finland. A geriatrician and nurse carried out structured clinical examinations and interviews with 601 persons, 523 of whom were living at home. RESULTS: Seventy percent (n = 364) of the elderly people were taking at least one analgesic, including most of those who suffered from daily interfering pain (85%) and nearly all of those experiencing daily pain at rest (93%). Nonsteroidal antiinflammatory drugs (NSAIDs; n = 226, 51%) and acetaminophen (n = 118, 23%) were the most commonly used analgesics. The use of opioids became more common with age, accounting for 16% of the drugs in the oldest patients (> or =85 y) and 6% among those aged 75-79 years. Analgesics were mainly taken when needed. Only 13% of NSAID users, 18% of acetaminophen users, and 21% of opioid users took these preparations regularly. CONCLUSIONS: Although analgesics are commonly used by elderly patients, it appeared that many patients were still experiencing daily interfering pain and pain at rest.     

Blood cell dynamics in P-selectin-deficient mice

P-selectin is expressed on the surfaces of activated platelets and endothelium where it mediates binding to leukocytes. P-selectin- deficient mice were shown to exhibit peripheral neutrophilia (Mayadas et al: Cell 74:541, 1993). We now show that this is not caused by changes in bone marrow precursors nor by a lack of neutrophil margination. Both P-selectin-positive and -negative animals displayed similar increases in peripheral blood neutrophil numbers after injection of epinephrine. However, clearance of 51Chromium-labeled neutrophils is delayed in mice deficient for P-selectin, indicating that the neutrophilia is at least in part the result of delayed removal. We detected no obvious alterations in lymphocyte differentiation, distribution, or adhesion to high endothelial venules in peripheral lymph nodes. Through intravital microscopy, we examined the impact of P-selectin deficiency on leukocyte/endothelial interaction beyond the initial stages of inflammation. Four hours after the administration of an inflammatory irritant, leukocyte rolling was observed even in the absence of P-selectin. There were significantly fewer rolling cells relative to wild-type mice, and their velocity was reduced. Moreover, in the peritonitis model, the number of peritoneal macrophages in wild-type mice increased threefold at 48 hours, whereas the macrophages in the mutant mice remained near baseline levels. Thus, whereas P-selectin is known to be involved in early stages of an inflammatory response, our results indicate that it is additionally responsible for leukocyte rolling and macrophage recruitment in more prolonged tissue injury.