Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.

Treatment of patients with HIV thrombocytopenia and hemolytic uremic syndrome with protein A (Prosorba column) immunoadsorption.

Both antibodies and circulating immune complexes (CIC), which bind to platelets and induce the destruction and clearance of platelets by the reticuloendothelial system, are found in patients with human immunodeficiency virus (HIV) and immune thrombocytopenic purpura (ITP). IgG and CIC were removed from patients' plasma by extracorporeal immunoadsorption using protein A-silica columns (PROSORBA columns). Of the 36 HIV-positive ITP patients treated, 29 received more than one treatment and were evaluated for response. Sixteen patients showed more than a 50% increase in their platelet counts. Platelet-associated IgG (PAIgG) and/or platelet-directed IgG and CIC were elevated in all patients. After four to eight treatments, 16 of 29 patients showed a 170% to 430% increase in platelet counts. A decrease in CIC and PAIgG was noted in responding patients. The median duration of response to date was 8 to 12 months. This treatment was associated with immune modulation and the development of an anti-F (ab')2 antibody response. The antibody functions by complexing with both platelet-binding IgG and CIC, neutralizing their binding capacity for platelets and enhancing their clearance from the circulation. Nine patients with mitomycin-C-induced hemolytic uremic syndrome (HUS) were also treated with PROSORBA columns. Pretreatment platelet counts were markedly reduced while a definite increase in platelet counts was observed upon completion of therapy. There was a decrease of hemolysis and stabilization of renal function in three patients. PROSORBA column treatment has demonstrated marked activity against both HIV-ITP and HUS, and has successfully freed patients from the bleeding diathesis associated with these syndromes.

Myasthenic crisis. Response to plasmapheresis following failure of intravenous gamma-globulin.

Myasthenic crisis is a potentially life-threatening complication of myasthenia gravis that requires aggressive therapy. We describe four patients in whom myasthenic crisis developed and who failed to respond to initial treatment with intravenous gamma-globulin. All four patients subsequently responded to intensive plasma exchange. Based on our experience, plasmapheresis appears to be superior to intravenous gamma-globulin for the treatment of myasthenic crisis in certain patients. Prognostic factors that determine the effectiveness of intravenous gamma-globulin vs plasmapheresis in these patients merit further investigation.

Repeat thymectomy in chronic refractory myasthenia gravis.

Encouraged by recent results with "extended" thymectomy in the treatment of myasthenia gravis, we carried out repeat thymectomy in six patients with chronic, refractory disease who did not initially have extended thymectomy. All were completely disabled with longstanding myasthenia. Initial thymectomy (four transsternal, one transcervical, and one substernal) was carried out at a mean of 8.9 years previously (range, 5 to 18). There was no residual thymus observed with CT, but at repeat thymectomy, residual thymic tissue was present in five of six patients. Five patients significantly improved and four returned to full-time work. Mean prednisone dose declined from 51 mg to 18 mg/d, and mean pyridostigmine dose fell from 1,290 mg to 415 mg/d. No patient to date has had a complete remission. These results suggest that repeat thymectomy may benefit some patients with chronic disabling myasthenia gravis, especially when it is uncertain from a review of the operative report whether all thymic tissue was removed at the initial thymectomy.

Inflammatory neuropathy in homosexual men with lymphadenopathy.

Twelve homosexual men had peripheral neuropathy with fever, night sweats, and lymphadenopathy. Sensory symptoms predominated, but there was also weakness and cranial nerve dysfunction. Manifestations were multifocal in nine and distal and symmetric in three. CSF was abnormal in all eight patients examined. Sural nerve in five patients showed axonal degeneration, accompanied in two by segmental demyelination. Four patients had epineurial and endoneurial perivascular chronic inflammatory cells without evidence of vasculitis. Neuropathy remitted spontaneously in six patients. Four patients received steroids without clinical response, although one later responded to plasmapheresis-lymphocytapheresis. Four patients later progressed to AIDS.

Mononeuritis multiplex associated with cryoglobulinemia in HIV infection.

We describe a patient with human immunodeficiency virus (HIV) infection who developed mononeuritis multiplex associated with polyclonal (type III) cryoglobulinemia. The patient's symptoms stabilized following treatment with plasmapheresis and removal of the cryoglobulin. Our case represents the first report of polyclonal cryoglobulinemia in HIV disease and suggests that cryoglobulinemia may play an etiologic role in some patients with HIV-associated neuropathy.

Lack of response to suramin in patients with AIDS and AIDS-related complex.

Forty-one homosexual men with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated with 0.5, 1.0, or 1.5 g of suramin weekly for up to six months. In no patient was evidence of symptomatic improvement or regression of Kaposi's sarcoma shown. Opportunistic infections developed in 16 patients during therapy. Only six patients (15 percent) became human immunodeficiency virus (HIV) culture-negative during treatment, despite documentation of adequate serum suramin levels. All but one of these six have had disease progression. Decreases in the numbers of total T4 cells with time were observed in both AIDS and AIDS-related complex subgroups. Toxicity was significant and consisted of fatigue, fever, and hepatic and renal dysfunction, all of which were observed most frequently with the 1.0 or 1.5 g dosages. Fatal hepatic failure developed in two patients, and adrenal insufficiency was documented in eight patients. Suramin is a toxic agent that shows no virologic, immunologic, or clinical benefit in patients with HIV-related disease.

Pilot study of topical dinitrochlorobenzene (DNCB) in human immunodeficiency virus infection.

Dendritic cells, the primary antigen presenting cells of the human immune system, are heavily infected with human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS). Dinitrochlorobenzene (DNCB) is a contact sensitizing agent that acts as a potent immune modulator of dendritic cells. In this pilot study, we examined the safety and efficacy of topical DNCB application in patients with early HIV disease. Topical DNCB was well tolerated by these patients, with an adverse reaction rate of 10%. CD4+ T-cell counts remained stable with repeated DNCB use. In contrast, CD8+ T-cell counts and natural killer cells increased significantly following DNCB sensitization. This increase in CD8+ T-cell and natural killer cell subsets was accompanied by a decrease in HIV replication, as measured by serum HIV RNA levels. Based on this pilot study, we conclude that topical DNCB is safe in early HIV disease and may decrease viral load via a systemic effect on dendritic cells, CD8+ T-cells and natural killer cells. These results require confirmation in larger controlled trials.

Chemical sympathectomy abolishes the increase in blood pressure of linoleic acid deficient fed rats induced by salt loading.

In previous experiments an altered PG biosynthesis as well as an increase in blood pressure, heart rate and plasma epinephrine could be found after a linoleic acid deficient diet compared with a linoleic acid rich diet in rats with a high salt intake. We injected rats with 200 micrograms 6-hydroxydopamine into the right and left cerebral ventricles 17 days before a four-week linoleic acid deficient diet (0.5 J% linoleic acid) and salt loading (1.5% NaCl). In these rats the elevation of blood pressure and plasma epinephrine compared with linoleic acid rich fed rats (13.3 J+ linoleic acid) was abolished and heart rate was reduced. PG biosynthesis in aorta and kidney medulla homogenate (PGE and PGF) and stomach fundus homogenate (6-Keto-PGF1 alpha) was not influenced by chemical sympathectomy, neither were the food and fluid intakes. We conclude that an enhanced adrenergic activity (via alterations in PG metabolism?) is involved in the blood pressure increase after a linoleic acid deficient diet under high salt intake.

Immune complex disease with fatal pulmonary hemorrhage: its occurrence in a patient with myasthenia gravis.

A man with ocular myasthenia gravis had rapidly progressing pulmonary hemorrhage, acute renal failure, arthralgias, and palpable purpura. Lung and skin biopsy specimens and subsequent autopsy revealed immunopathological changes consistent with immune complex disease. Patients with myasthenia gravis may represent a group at risk for immune complex disease.

Experimental models of hypertension.

The article presents a review of experimental modelling of hypertension with the purpose helping research on its pathogenetical mechanisms, its characteristic, its therapy and eventual prophylaxy. Both conventional and genetic experimental models of inducing hypertension are discussed. The paper comprises a short description of the methods, their possibilities, the form of human hypertension to which each model corresponds, as well as the most important peculiarities of the alterations which are induced by the corresponding method. Special attention was paid to the most recent models of genetically determined spontaneous hypertension including spontaneously hypertensive rats (SHR-Okamoto-Aoki), the New Zealand strain of genetic hypertension (GH-Smirk), the stroke prone and stroke resistant substrains of SHR (SHRSP and SHRSR), arteriolipoidosis prone SHR (SHRLP), the obese SHR stain, the Milan hypertensive (MHS), Dahl's salt susceptible (s) and salt resistant (R) strains, and Smirk's genetic hypotensive strain of rats.