Studies of scorpion antivenins. 2. Venom collection and scorpion colony maintenance

This paper describes methods used successfully in a large-scale programme for the collection of scorpion venom. Effective methods were developed for the maintenance of a laboratory colony of over 5000 adult scorpions. Electrical stimulation of the scorpions to induce venom emission was greatly facilitated by tranquillizing them with CO₂ and using a slightly modified, snap-type mousetrap as a scorpion-holding device. This technique made for rapid handling of specimens with little risk to the technicians and minimal trauma to the scorpions. Specimens held under proper conditions yielded venom from six to eight times at two-week intervals. As much as 66.4% of the venom content of the telson was emitted by an electrically stimulated scorpion. Venom collected in this manner was air-dried at room temperature, then placed in a calcium chloride desiccator and stored at 44° F (6.6° C). Venoms of medically important scorpions from Mexico, Brazil, Israel, India, Panama and the USA were collected during this programme.     

Granulomatous Hepatitis of Obscure Aetiology: DIAGNOSTIC CONTRIBUTION OF KVEIM TESTING AND ANTI-TUBERCULOUS THERAPY

Five unusual cases of granulomatous hepatitis are described.The diagnostic problems posed by each case are discussed indetail, specifically the difficulties encountered in establishinga firm aetiological factor even after comprehensive investigation. Two patients with widely disparate clinical and pathologicalfindings demonstrated a positive Kveim test. Despite thoroughsearch, neither showed any clinical evidence of conventionalsarcoidosis and in one case lymph-node histology was repeatedlynegative for sarcoid granulomata. The significance of thesecases and the current status of the Kveim tests are discussed.It is postulated that these two patients may fit into an expandingspectrum of conditions characterized by Kveim test positivity.This currently embraces: (i) sarcoidosis; (ii) Crohn's disease,both human and experimental; and (iii) ‘normal’subjects who fail to convert tuberculin positivity after B.C.G.vaccination. To these we would add a number of patients withidiopathic granulomatous hepatitis. It is suggested that theKveim test represents an histopathological expression of abnormalhost reactivity common to a variety of conditions in which inter-relatedor cross-reacting antigens occur. Although tubercle bacilli were not isolated, two further patientswere adjudged to have hepatic granulomata of tuberculous originon the basis of a suspicious clinical history and an unequivocalresponse to specific chemotherapy. In a third patient a trialof anti-tuberculous therapy obscured the true diagnosis of brucellosisfor several years. The role of trials of anti-tuberculous therapyin cases of granulomatous hepatitis of unknown aetiology isdiscussed.     

Effect of assay specificity on the association of urine 11‐dehydro thromboxane B2 determination with cardiovascular risk

Summary. Background: Elevated urine 11‐dehydro TXB₂, an indicator of persistent thromboxane generation in aspirin‐treated patients, correlates with adverse cardiovascular outcome and has recently been identified as an independent risk factor for vein graft thrombosis after cardiac bypass surgery in the Reduction in Graft Occlusion Rates (RIGOR) study. The polyclonal antibody‐based ELISA used to measure 11‐dehydro TXB₂ in these previous studies is no longer clinically available and has been supplanted by a Food and Drug Administration (FDA)‐cleared second‐generation monoclonal antibody‐based ELISA. Objectives: To compare the laboratory and clinical performance of the first‐ and second‐generation assays in a well‐defined study population. Methods: 11‐dehydro TXB₂ was quantified in 451 urine samples from 229 Reduction in Graft Occlusion Rates (RIGOR) subjects using both ELISA. Ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) and spiking studies were used to investigate discordant assay results. The association of 11‐dehydro TXB₂ to clinical outcome was assessed for each assay using multivariate modeling. Results: Median 11‐dehydro TXB₂ levels were higher by monoclonal antibody‐ compared with polyclonal antibody‐based ELISA (856 vs. 399 pg mg^?1 creatinine, P < 0.000001), with the latter providing values similar to UPLC‐MS/MS. This discrepancy was predominantly as a result of cross‐reactivity of the monoclonal antibody with 11‐dehydro‐2,3‐dinor TXB₂, a thromboxane metabolite present in a similar concentration but with a poor direct correlation with 11‐dehydro TXB₂. In contrast to the first‐generation ELISA, 11‐dehydro TXB₂ measured by the monoclonal antibody‐based ELISA failed to associate with the risk of vein graft occlusion. Conclusion: Quantification of urine 11‐dehydro TXB₂ by monoclonal antibody‐based ELISA was confounded by interference from 11‐dehydro‐2,3‐dinor TXB₂ which reduced the accuracy and clinical utility of this second‐generation assay.