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.     

Selected gastrointestinal pathologies in tropical sub-Saharan Africa.

Doctors need to be well informed about differences in the presentation of certain diseases in tropical and temperate climates. In this article the characteristics of some gastrointestinal diseases, as they recur in sub-Saharan Africa, are briefly reviewed. Diseases of the stomach--including ulcertaion and cancer--are uncommon in Africa, although duodenal ulcer is common all over the tropics. In contrast, colorectal cancer is an extremely rare illness in sub-Saharan Africa, while hepatocellular carcinoma is much commoner than in Europe or North America and the very high incidence of this tumour in tropical countries is cause for concern.     

The occurrence of Chlamydia trachomatis in the semen of men participating in an IVF programme

Chlamydia trachomatis is one of the most common causative agentsof sexually transmitted diseases. The authors studied the occurrenceof C.trachomatis in the semen of 184 asymptomatic men participatingin the IVF programme. Twenty-six (14.1%) of the 184 tested werepositive for C.trachomatis, these patients and their wives receivingdoxycycline capsules twice, 100 mg on the first day and 100mg/day for the following 13 days. This treatment was effectivein 88.5% of the cases and in the rest, treatment continued witherithromycin 250 mg four times/day for 2 weeks. The authorscompared the semen parameters (cell count, motility, morphology,bovine mucus penetration and hypo-osmotic swelling test) inthe infected and non-infected groups and observed no significantdifference between these two groups     

Prostacyclin acts in rat gastric (fundic) mucosa via the intracellular ‘second messenger system’

Using a specific radioimmunoassay technique it seems that Prostacyclin (PG-I₂) has a strong effect on the cyclic nucleotide content of the rat gastric (fundic) mucosa. 1 min after an intragastric application of 100 g/kg PG-I₂ the cAMP-content and in the 5th min the cGMP-content showed a highly significant decrease. It seems that the basic mechanism of action of PG-I₂ is a typical hit and run effect, acting on the intracellular second messenger system.     

Evidence for proteolytic cleavage of covalently bound protein A from a silica based extracorporeal immunoadsorbent and lack of relationship to treatment effects

Studies were conducted to evaluate the potential cause for release of covalently bound Staphylococcal protein A (SpA) from a silica based extracorporeal immunoadsorbent matrix. In vitro tests revealed that SpA could be detected in human plasma, human serum, and chicken serum upon exposure to the immunoadsorbent matrix which had been treated to remove non-covalently bound SpA. In contrast, only minute quantities of SpA were detected after exposure of a physiologic mixture of purified albumin and immunoglobulin G (IgG) to the immunoadsorbent matrix. Additional tests, employing a cocktail of protease inhibitors and formalin as a general stabilizer and protease inhibitor, revealed significant inhibition of endogenous proteolytic activity present in plasma and serum. Prevention of this proteolytic activity also significantly inhibited the release of covalently bound SpA from the immunoadsorbent matrix upon contact with plasma or serum samples. Further analyses of serum samples from patients with immune thrombocytopenia, chemotherapy associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, and breast cancer revealed a lack of association between the quantity of SpA proteolytically released and observed clinical responses or adverse effects experienced during immunoadsorption treatments. These studies indicate that SpA detected in plasma or serum after exposure to the immunoadsorbent is due to inherent endogenous proteolytic activity which cleaves protein fragments from the matrix and that these cleaved SpA fragments do not appear to contribute to the observed clinical responses or adverse effects in treated patients.     

PRENATAL DETECTION OF THE DELTA F 508 MUTATION USING FLUORESCENT PCR AND COMPARISON OF THE RESULTS WITH CONVENTIONAL PCR

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasians. The most frequent mutation associated with cystic fibrosis has been identified as the 3 bp deletion Delta F 508. While existing polymerase chain reactions (PCR) (allele specific amplification) used to screen for CF are both sensitive and specific, we tested the prenatal application of fluorescent polymerase chain reaction and subsequent DNA fragment analysis that appears to be fast and sensitive. DNA samples (n=146) isolated from amniotic fluid (n=108), chorion villus biopsies (n=6), and human peripheral blood (n=32) were analyzed for the presence of Delta F 508 using the fluorescent method. Of these, 10 carriers of Delta F 508 mutation were detected. We achieved the same results with conventional PCR and fluorescent PCR.     

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4⁺ and CD8⁺ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.