Interventional radiology techniques for the diagnosis of lymphoma or leukemia

BACKGROUND: Fluid aspiration, percutaneous biopsy, and catheter drainage are standard minimally invasive methods of diagnosing lymphoma or leukemia in adults. OBJECTIVE: To determine the effectiveness of interventional radiologic techniques in diagnosing specific hematologic malignancies in children. METHODS: During a 4-year period, 22 patients (16 male, 6 female; median age, 13 years) underwent 25 percutaneous biopsies, 6 fluid aspirations, 3 catheter drainages, and 1 needle localization for diagnosing suspected hematologic malignancy. RESULTS: For Hodgkin's disease, the procedures yielded 6 true-positive (TP) results, 2 true-negative (TN) results, and 2 false-negative (FN) results; for non-Hodgkin lymphoma (NHL), 14 TP results, 1 TN result, and 3 FN results; and for leukemia, 4 TP results and 3 FN results. Percutaneous biopsies yielded 16 TP results, 3 TN results, and 6 FN results. Aspirations and drainages yielded 8 TP results and 1 FN result. The one needle localization yielded a FN result. Overall sensitivity was 75%+/-7.3%; specificity, 100%; and accuracy, 77%+/-7.1%. CONCLUSION: Percutaneous biopsy of lymphoma is usually diagnostic. Drainage or aspiration of a fluid collection associated with NHL or leukemia is often diagnostic and is less invasive than biopsy. These procedures are minimally invasive and effective for diagnosing pediatric hematologic malignancies.     

Mecamylamine acutely increases human intravenous nicotine self-administration

Previous studies of human cigarette smoking have shown that administration of the nicotinic acetylcholine receptor antagonist mecamylamine produces acute increases in smoking behavior. In contrast, studies of intravenous nicotine self-administration in animals typically show an immediate decrease in self-administration behavior following mecamylamine administration. To investigate whether this discrepancy might be due in part to the mode of nicotine self-administration (intravenous vs. cigarette smoke), we measured the rate of intravenous nicotine self-administration in tobacco-dependent human smokers. After being trained in a preliminary session to self-administer puff-sized bolus doses of nicotine, 16 subjects were exposed to two sessions (4 h duration) in which they could self-administer intravenous nicotine ad lib. Two hours prior to one session, subjects swallowed a capsule containing 10 mg mecamylamine, and before the other session they took a placebo capsule. Rates of responding for nicotine were assessed, as were subjective reports of withdrawal symptoms and plasma nicotine levels. There was a significantly higher rate of nicotine self-administration in the mecamylamine condition, and mecamylamine attenuated the reduction in craving over the session that occurred during nicotine self-administration. These results indicate that route of administration is not likely the major source of the discrepancy between findings from animal and human studies of nicotine administration. Instead, it is likely that the higher rates of nicotine self-administration induced by mecamylamine were due to an attenuation of the effects of nicotine (e.g., alleviation of withdrawal symptoms) in nicotine-dependent subjects. Thus, animal models of nicotine dependence may need to be employed in conjunction with self-administration procedures in order to duplicate the effects of mecamylamine observed in studies of human smokers.     

Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout mice

1 Urotensin-II (U-II) is among the most potent mammalian vasoconstrictors identified and may play a role in the aetiology of essential hypertension. Currently, only one mouse U-II receptor (UT) gene has been cloned. It is postulated that this protein is solely responsible for mediating U-II-induced vasoconstriction. 2 This hypothesis has been investigated in the present study, which assessed basal haemodynamics and vascular reactivity to hU-II in wild-type (UT((+/+))) and UT receptor knockout (UT((-/-))) mice. 3 Basal left ventricular end-diastolic and end-systolic volumes/pressures, stroke volumes, mean arterial blood pressures, heart rates, cardiac outputs and ejection fractions in UT((+/+)) mice and in UT((-/-)) mice were similar. 4 Relative to UT((+/+)) mouse isolated thoracic aorta, where hU-II was a potent spasmogen (pEC(50)=8.26+/-0.08) that evoked relatively little vasoconstriction (17+/-2% 60 mM KCl), vessels isolated from UT((-/-)) mice did not respond to hU-II. However, in contrast, the superior mesenteric artery isolated from both the genotypes did not contract in the presence of hU-II. Reactivity to unrelated vasoconstrictors (phenylephrine, endothelin-1, KCl) and endothelium-dependent/independent vasodilator agents (carbachol, sodium nitroprusside) was similar in the aorta and superior mesenteric arteries isolated from both the genotypes. 5 The present study is the first to directly link hU-II-induced vasoconstriction with the UT receptor. Deletion of the UT receptor gene results in loss of hU-II contractile action with no 'nonspecific' alterations in vascular reactivity. However, as might be predicted based on the limited contractile efficacy recorded in vitro, the contribution that hU-II and its receptor make to basal systemic haemodynamics appears to be negligible in this species.     

Minimax two-stage-designs with applications to tissue banking case-control studies

'Tissue banks' are created, at least in part, to help medical scientists learn about disease biology on the basis of samples provided by patients on treatment protocols that were competed years earlier.The bank inventory consists of precious non-renewable patient material (such as frozen diagnostic blood or bone marrow), which can be linked to both clinical data and long term follow-up information. Case-control studies, where cases represent clinical failures and controls clinical successes, are ideal for rapidly learning if a laboratory marker might have prognostic significance. While group sequential (multi-stage) methods are widely used in clinical trials, they have rarely been applied in case-control studies. Further, unlike clinical trials where safety and efficiency may actually be in conflict, case-control studies can focus on efficiency. Hence, minimizing the expected sample size is a desirable goal in such a setting. Since the true effect size is never known, and since no prior distribution can be postulated for the effect size, we have opted for the minimax solution. A strategy is developed to determine amongst all two-stage designs with given type I and type II errors, the one for which the maximum expected sample size is minimized. The user is provided with simple tables, whereby one can determine everything necessary to conduct the study from the corresponding calculation for a single-stage design. A matched pair example is given where the suggested design can be modified, to obtain a superior 'two-plus' stage design. The basic idea is to conduct the first stage as planned, but use the estimate of variance to redesign the study, without using the estimate of effect size in the redesign.     

The peptidic urotensin-II receptor ligand GSK248451 possesses less intrinsic activity than the low-efficacy partial agonists SB-710411 and urantide in native mammalian tissues and recombinant cell systems

Several peptidic urotensin-II (UT) receptor antagonists exert 'paradoxical' agonist activity in recombinant cell- and tissue-based bioassay systems, likely the result of differential urotensin-II receptor (UT receptor) signal transduction/coupling efficiency between assays. The present study has examined this phenomenon in mammalian arteries and recombinant UT-HEK (human embryonic kidney) cells.BacMam-mediated recombinant UT receptor upregulation in HEK cells augmented agonist activity for all four peptidic UT ligands studied. The nominal rank order of relative intrinsic efficacy was U-II>urantide ([Pen(5)-DTrp(7)-Orn(8)]hU-II(4-11))>SB-710411 (Cpa-c[DCys-Pal-DTrp-Lys-Val-Cys]-Cpa-amide)>GSK248451 (Cin-c[DCys-Pal-DTrp-Orn-Val-Cys]-His-amide) (the relative coupling efficiency of recombinant HEK cells was cat>human>rat UT receptor). The present study further demonstrated that the use of high signal transduction/coupling efficiency isolated blood vessel assays (primate>cat arteries) is required in order to characterize UT receptor antagonism thoroughly. This cannot be attained simply by using the rat isolated aorta, an artery with low signal transduction/coupling efficiency in which low-efficacy agonists appear to function as antagonists.In contrast to the 'low-efficacy agonists' urantide and SB-710411, GSK248451 functioned as a potent UT receptor antagonist in all native isolated tissues studied (UT receptor selectivity was confirmed in the rat aorta). Further, GSK248451 exhibited an extremely low level of relative intrinsic activity in recombinant HEK cells (4-5-fold less than seen with urantide). Since GSK248451 (1 mg kg(-1), i.v.) blocked the systemic pressor actions of exogenous U-II in the anaesthetized cat, it represents a suitable peptidic tool antagonist for delineating the role of U-II in the aetiology of mammalian cardiometabolic diseases.     

Circulating immune complexes in kidney diseases: pathogenic significance, methods of proof, problems, tendencies

The tendency to recognize immune complexes already before their deposition in the tissue led in the seventies to the development of numerous methods of estimation for immune complexes in the serum and to the proof of these complexes in many diseases. The author enters these methods and their problems, the results got up to now for renal diseases, i. e. above all for glomerulonephritides, are cited in form of theses. Among others belong to this the establishments that the proof of circulating immune complexes cannot contribute to the diagnosis, but to the control of the activity of the diseases and of the therapeutic effect. Recently, research concerning immune complexes yielded remarkable results as to their role as regulating factors of the unspecific as well as of the specific defense mechanisms of the organism. This promises that further clarifications on etiology and genesis particularly of diseases of the immune complex type are to be expected, among them also for glomerulonephritides.