HIV/AIDS and the risk of deep vein thrombosis: a study of 45 patients with lower extremity involvement.

Many aspects of acquired immunodeficiency syndrome (AIDS) have been described in detail in the literature. However, there have been very few articles on the phenomenon of deep vein thrombosis (DVT) in the lower extremities of human immunodeficiency virus (HIV)/AIDS patients. The objective of this communication is to record the incidence of DVT in HIV/AIDS patients and the risks for development of embolic events and to emphasize the need for prevention and for the vigorous treatment of this complication. We conducted a retrospective review of HIV/AIDS-infected patients with DVT admitted to Mount Sinai School of Medicine/Cabrini Hospital in New York during the last 5 years. Analysis includes demographic data; risk factors for HIV/AIDS infection; associated medical problems; recent surgery; and laboratory findings including CD4 counts, platelet counts, prothrombin times, partial thromboplastin times, and plasma albumin levels; and image studies. From January 1995 to January 2000 4752 HIV/AIDS-infected patients were admitted. Of those admitted to the hospital 45 (0.95%) were found to have DVT. There were 36 males and nine females (mean age 43 years). Of the 45 patients 38 had infectious complications and 13 developed a malignancy. The distribution of the thromboses were the femoral vein in 23 patients, the popliteal vein in 20 patients, and the iliofemoral system in 2 patients. Twelve patients had recurrent DVT and three patients developed a pulmonary embolism. HIV/AIDS infection is a considerable risk for development of DVT in the lower extremity. Statistically DVT in HIV/AIDS is approximately 10 times greater than in the general population. Emphasis upon prevention and vigorous treatment of DVT is recommended.

Surgical treatment of HIV-related immune thrombocytopenia.

Immune related thrombocytopenia has been described extensively in patients infected with the human immunodeficiency virus (HIV). The efficacy and safety of splenectomy performed in 21 patients affected with HIV-related immune thrombocytopenia (platelet count less than 50,000/mm3), between 1992 and 1996, were evaluated. All the patients were symptomatic and had failed medical therapy. Nine of them were affected with acquired immune deficiency syndrome (AIDS), whereas 12 were HIV-positive (non-AIDS). In all the patients, a pre-operative bone marrow biopsy revealed increased megakaryocytes. Follow-up ranged from 5-16 months. The response rate to splenectomy (platelet count greater than 100,000/mm3) in the AIDS group was 83%, as opposed to 100% in the HIV-positive (non-AIDS) group. During the follow-up period, 19 of the 21 patients maintained platelet counts greater than 98,000/mm3; of the two non-responders, one patient expired 3 weeks after surgery, and a second patient had never responded. None of the HIV-positive (non-AIDS) patients developed AIDS during the follow-up period. All the complications observed (24%) were treated without sequelae. Based on these data, splenectomy can be considered safe and effective in treating patients with symptomatic HIV-related thrombocytopenia, when medical therapy has failed. Moreover, splenectomy did not appear to adversely affect the rate of conversion from the HIV-positive to the AIDS status, nor did it accelerate the progression of the disease in patients already diagnosed with AIDS.

Bradykinin increases cytosolic free [Ca2+] in proximal tubule cells.

The role of bradykinin (BK) as a calcium-mobilizing agonist in cells of renal proximal tubule origin was examined. Experiments were performed on confluent cultures of rabbit proximal tubule cells in primary culture and changes in cytosolic free Ca2+ concentration, [Cai2+], were monitored by use of the Ca2+-sensitive fluorescent probe fura-2. Under steady-state conditions, [Cai2+] was 210 +/- 7 nM in a Ca2+-replete medium vs. 135 +/- 5 nM in a medium devoid of Ca2+. Acute challenge with BK resulted in a transient increment in [Cai2+], which peaked at 150% the resting value within 10 s and was independent of medium [Ca2+]. The K0.5 for the process was 2.5 X 10(-10) M. The BK receptor displayed properties of the beta 2-variety. In a Ca2+-free medium 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) blocked the BK-elicited Ca2+ transient in a time- and dose-dependent manner. In contrast to TMB-8, the Ca2+-channel inhibitor, verapamil, was without effect. Prior exposure of cells to ionomycin completely obviated the BK-induced Ca2+ transient. Cells challenged with BK were nonresponsive to subsequent challenge by a second Ca2+-mobilizing agonist, angiotensin II (ANG II). In summary, these data suggest that BK is an extremely sensitive activator of the phosphoinositol transduction pathway in rabbit proximal tubule cells. Furthermore, the heterologous desensitization between BK and ANG II, in terms of elevating [Cai2+], suggests that these two agonists release Ca2+ from a common intracellular store.

Skin necrosis in the presence of paclitaxel and fluorometholone.

Paclitaxel (Taxol) can induce full-thickness skin necrosis at sites distant from those of injection. This side effect may be potentiated in the presence of fluorometholone (FML).

Differential effects of phorbol esters on PGE2 and bradykinin-induced elevation of [Cai2+] in MDCK cells.

Prostaglandin (PG) activation of the phosphoinositol transduction pathway in MDCK cells and modulation of this process by phorbol esters was studied by monitoring changes in cytosolic free Ca2+ concentration, [Cai2+], with the Ca2+-sensitive fluorescent probe, fura-2 and measurement of stimulation of inositol phosphates by anion-exchange chromatography. Cells challenged with PGE1 or PGE2 responded with a prompt and transient increase in [Cai2+] that was independent of extracellular Ca2+. The K0.5 for PGE2 for the process was 6.1 X 10(-7) M. PGE1 and PGE2 appeared to be recognized by a common receptor. PGF2 alpha was without effect. 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) but not verapamil, a Ca2+ channel inhibitor, blocked the PGE2-evoked Ca2+ transient. Under identical conditions PGE2 increased inositol phosphate accumulation by 54 +/- 8% (inositol-1-monophosphate), 23 +/- 6% (inositol-1,4-bisphosphate), and 49 +/- 3% (total inositol trisphosphate), above control values. Brief (30-60 s) exposure of cells to phorbol-12,13-myristate (PMA) or phorbol-12,13-dibutyrate (PDB) completely blocked the PGE2-induced Ca2+ transient. The K0.5 for the process for PMA and PDB was 0.3 +/- 0.1 and 4.5 +/- 2.2 nM, respectively. Neither 4 alpha-nor 4 beta-phorbol, which lack the ability to activate protein kinase C, were effective in this regard. In contrast to complete blockade by 10(-8) PMA of the PGE2 (10(-5) M)-elicited Ca2+ transient, this concentration of PMA inhibited the Ca2+ transient evoked by 10(-9) M bradykinin (BK) by 50%. In fact 10(-4) M PMA only partially blocked the BK-elicited Ca2+ transient. In summary, in MDCK cells, the PG receptor is coupled both to the adenylate cyclase system and inositol phospholipid transduction pathway. The PG receptor appears to be regulated by protein kinase C. In addition to protein kinase C other factors regulate the BK receptor.

Platelet-activating factor attenuates the arginine vasopressin-induced fall of transepithelial resistance across inner medullary collecting duct monolayers.

Platelet-activating factor (PAF) is a vasoactive substance produced in the medulla which may alter Na excretion by the kidney. To examine a possible site and mechanism of action of PAF on the kidney, we evaluated the effects of PAF on transepithelial resistance and intracellular calcium concentration ([Ca2+]i) in cultured rat inner medullary collecting duct cells. Exposure of inner medullary collecting duct (IMCD) cell monolayers to PAF had no significant effect on basal transepithelial resistance. By contrast, incubation of IMCD cells with PAF reversibly blocked the fall in transepithelial resistance induced by arginine vasopressin (AVP): -11.1 +/- 1.4 omega.cm2 with AVP versus -0.02 +/- 1.6 omega.cm2 with PAF and AVP. Exposure of IMCD cells to PAF in Ca-replete medium caused a rise in intracellular calcium from 155 +/- 25 to 491 +/- 68 nM. By contrast, exposure of IMCD cells to PAF in Ca-free medium produced no change in [Ca2+]i. Because the rise in [Ca2+]i induced by PAF was absent in Ca-free medium, transepithelial resistance across IMCD monolayers was examined in calcium-free medium. The effect of PAF to block the fall in transepithelial resistance induced by AVP was maintained in Ca-free medium. These data suggest that PAF modulates the effect of AVP on conductive channels by a mechanism distinct from changes in intracellular calcium.