Evaluation of anti-C1q capture assay for detecting circulating immune complexes and comparison with polyethylene glycol-immunoglobulin G, C1q-binding, and Raji cell methods.

An anti-C1q capture method kit (C1q-immunoglobulin G [IgG]) (Ortho Diagnostics, Inc., Raritan, N.J.) for measuring circulating immune complexes (CIC) was evaluated. The kit showed poor diagnostic sensitivity (P less than 0.005) for identifying CIC in patients with systemic lupus, rheumatoid arthritis, and bacterial endocarditis, as compared with polyethylene glycol-IgG and Raji cell tests (12, 24, and 24 positive, respectively, of 31 patients). Of the patients who were positive with the C1q-IgG test, 25% showed discrepancies when their results were compared with the polyethylene glycol-IgG and C1q-binding test results. Gel filtration chromatography of two of these discrepant sera showed the only peak of C1q-IgG activity to be associated with monomeric IgG (molecular weight, less than 200,000). We concluded that the kit method may be measuring substances other than CIC in some sera, because molecules of C1q attached to IgG should exhibit a molecular weight of greater than 500,000.     

Uncovering psychiatric test information with graphical techniques of Exploratory Data Analysis.

This article illustrates how Exploratory Data Analysis (EDA) can complement conventional statistical methods in evaluating psychiatric tests. Using one recent EDA computer program, we evaluated the ability of repeated psychiatric screening tests (the General Health Questionnaire [GHQ]) to predict medical and psychiatric service use in a Health Maintenance Organization (HMO), the Harvard Community Health Plan (HCHP). Using a stratified random sample of 244 new HCHP enrollees and viewing three-dimensional graphs of their data from multiple perspectives, we found two subpopulations: low GHQ scorers, for whom the tests did not predict service use; and high scorers, for whom they did. Surprisingly, improving scores forecast increased use and chronically high scores predicted diminished use. Using another stratified random sample of 213 new HCHP enrollees, and with scatterplot matrices from another interactive computer program, we found that high and unchanging GHQ scores forecast HMO dropout. We examine possible interpretations--for example, that chronically distressed patients may become immobilized, diminish service use, and ultimately leave the HMO. We also explain how EDA methods may help uncover elusive results in other data (e.g., mental health outcomes).     

Radical cystectomy after coronary artery bypass graft

Nine patients have undergone single-stage radical cystectomy and ileal conduit urinary diversion two to fifty-one months after coronary artery bypass procedures. Two patients presenting with intractable angina at the time their malignant disease was being evaluated required bypass surgery before cystectomy could be undertaken. No significant cardiac morbidity occurred postoperatively, and all remain alive without evidence of malignant disease.     

Positron emission tomographic investigations of central muscarinic cholinergic receptors with three isomers of [76Br]BrQNP

We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[⁷⁶Br]BrQNP,E(-,-)-[⁷⁶Br]BrQNP andE(-,+)-[⁷⁶Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [⁷⁶Br]BrNH₄ and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M₂ selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M₁ selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., theE(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively.Z(-,-)-[⁷⁶Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for theE(-,+)-[⁷⁶Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors.Z(-,-)-[⁷⁶Br]BrQNP, which is displaced in higher amounts from M₂ mAChR-enriched structures, reveals an M₂ affinity. The two isomers having the (-,-)-configuration are potential probes for investigating central muscarinic receptors. The absolute configuration on the acetate chiral centre influences their muscarinic subtype selectivity and thecis-trans isomerism of the vinyl moiety affects their specific fixation.