Serum transferrin receptor concentration is not indicative of erythropoietic activity in chronic hemodialysis patients with poor response to recombinant human erythropoietin

BACKGROUND: Serum transferrin receptor (sTfR) is a transmembrane glycoprotein derived from erythroid precursors in the bone marrow. Its concentration provides a quantitative measure of total erythropoietic activity and an indication of functional iron deficiency. This study was conducted to investigate whether sTfR is a useful index of erythropoietic activity in chronic hemodialysis patients with poor response to maintenance recombinant human erythropoietin (rHuEPO) therapy. METHODS: Using an enzyme-linked immunosorbent assay, sTfR concentration was measured in 67 uremic patients who had been on hemodialysis for a mean of 42 months (3-242 months). rHuEPO was administered three times a week to keep the hematocrit above 30%. Hemoglobin, red blood cell indices, serum ferritin, serum total iron binding capacity and unsaturated iron binding capacity were determined. Of the 67 patients, 35 who responded favorably to rHuEPO with hematocrits above 30% were categorized as Group I and 32 who did not attain the target hematocrit were categorized as Group II. As a control group, 31 healthy subjects were also investigated. RESULTS: The serum iron, ferritin, transferrin iron saturation, dialysis efficiency and nutritional state were not different between groups of hemodialysis patients. The mean sTfR concentration was 2.1 +/- 0.6 micrograms/ml (range, 1.15-3.53 micrograms/ml) in Group I patients, compared with 1.9 +/- 0.9 micrograms/ml (range, 1.03-2.65 micrograms/ml) in Group II. The difference was not significant. In addition, the mean sTfR concentration of 1.8 +/- 0.4 micrograms/ml (range, 0.86-2.76 micrograms/ml) in the healthy controls was not significantly different from Groups I and II. CONCLUSIONS: sTfR concentration cannot be used to distinguish good from poor rHuEPO responders among chronic hemodialysis patients who have elevated serum ferritin (> 300 micrograms/l) and transferrin iron saturation (> 25%) during the course of maintenance rHuEPO therapy.     

Alternative locations for internal defibrillator electrodes

Successful defibrillation is described in two patients in whom the defibrillating electrode was positioned in the coronary sinus and right ventricular outflow tract as alternative sites. Internal cardiac defibrillation has been successful with single or multiple endocardial electrodes, epicardial patch electrodes, and subcutaneous surface electrodes (patch, array) in varying combinations and recently with an active can electrode. While the traditional location of the endocardial electrode has been the right ventricular apex, we describe two patients in whom defibrillation was successful in alternate locations, the coronary sinus and the right ventricular outflow tract.     

Why behavior analysts should study emotion: the example of anxiety

Historically, anxiety has been a dominant subject in mainstream psychology but an incidental or even insignificant one in behavior analysis. We discuss several reasons for this discrepancy. We follow with a behavior-analytic conceptualization of anxiety that could just as easily be applied to emotion in general. Its primary points are (a) that languageable humans have an extraordinary capacity to derive relations between events and that it is a simple matter to show that neutral stimuli can acquire discriminative functions indirectly with no direct training; (b) that private events can readily acquire discriminative functions; (c) that anxiety disorders seem to occur with little apparent direct learning or that the amount of direct learning is extraordinarily out of proportion with the amount of responding; and (d) that the primary function of anxious behavior is experiential avoidance. We conclude that the most interesting aspects of anxiety disorders may occur as a function of derived rather than direct relations between public events and overt and private responses with avoidance functions. Implicit in this conclusion and explicit in the paper is the assertion that anxiety is a suitable subject for behavior-analytic study.     

Localized mucosal involvement and severe pulmonary involvement in a young patient with paraneoplastic pemphigus associated with Castleman''s tumour

OBJECTIVES: This study examined the impact of state legislation on mammography quality and access in Michigan. METHODS: The impact of state legislation was analyzed with respect to utilization, numbers of machines and facilities, and image quality. RESULTS: The legislation had a positive effect on image quality improvement, had no impact on utilization by women aged 50 years and above, and resulted in few facility closures. CONCLUSIONS: Michigan's legislative intervention appears to have had a positive effect on efforts to improve mammography quality assurance with implications for other federal and state efforts to achieve quality assurance in health care delivery.     

Molecular characterization of a novel Rickettsia species from Ixodes scapularis in Texas

Triclosan (Irgasan) is a broad spectrum antimicrobial agent used in handsoaps, toothpastes, fabrics, and plastics. It inhibits lipid biosynthesis in Escherichia coli, probably by action upon enoyl reductase (FabI) (McMurry, L.M., Oethinger, M. and Levy, S.B. (1988) Nature 394, 531-532). We report here that overexpression of the multidrug efflux pump locus acrAB, or of marA or soxS, both encoding positive regulators of acrAB, decreased susceptibility to triclosan 2-fold. Deletion of the acrAB locus increased the susceptibility to triclosan approximately 10-fold. Four of five clinical E. coli strains which overexpressed marA or soxS also showed enhanced triclosan resistance. The acrAB locus was involved in the effects of triclosan upon both cell growth rate and cell lysis.     

Germline mutations of the BRCA1 and BRCA2 genes in a breast and ovarian cancer patient

Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM and 1000 nM ANG II increased NO-oxidation current by 85+/-18 pA (n = 11), 148+/-22 pA (n = 11), and 193+/-29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4+/-0.5 nM, 6.1+/-1.1 nM, and 8.2+/-1.3 nM, respectively. Neither LOS (1 muM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers markedly blunted NO release in response to ANG II (10 nM): 77+/-6% inhibition with LOS (n = 8) and 63+/-9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries, and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent NO release.     

Cloning and functional characterization of the 5''-flanking region of human methionine adenosyltransferase 2A gene

Electron microscopy of dimeric and trimeric single chain antibody Fv fragments (scFvs) complexed with anti-idiotype Fab fragments was used to reveal the orientation of antigen binding sites. This is the first structural analysis that discloses the multivalent binding orientation of scFv trimers (triabodies). Three different scFv molecules were used for the imaging analysis; NC10 scFv-5 and scFv-0, with five- and zero-residue linkers respectively between the VH and VL domains, were complexed with 3-2G12 anti-idiotype Fab fragments and 11-1G10 scFv-0 was complexed with NC41 anti-idiotype Fab fragments. The scFv-5 molecules formed bivalent dimers (diabodies) and the zero-linker scFv-0 molecules formed trivalent trimers (triabodies). The images of the NC10 diabody-Fab complex appear as boomerangs, not as a linear molecule, with a variable angle between the two Fab arms and the triabody-Fab complexes appear as tripods.     

Initial experience with endovascular aneurysm repair: comparison of early results with outcome of conventional open repair

PURPOSE: To determine the safety, effectiveness, and problems encountered with endovascular repair of abdominal aortic aneurysm (AAA). Initial experience with endoluminal stent grafts was examined and compared with outcome for a matched concurrent control group undergoing conventional operative repair of AAA. METHODS: Over a 3-year period, 30 patients underwent attempts at endovascular repair of infrarenal AAA. Of the 28 (93%) successfully implanted endografts, 8 were tube endografts, 8 bifurcated grafts, and 12 aortouniiliac grafts combined with femorofemoral bypass. Most of the procedures were performed in the past year because the availability of bifurcated and aortoiliac endografts markedly expanded the percentage of patients with AAA who might be treated with endoluminal methods. The follow-up period ranged from 1 to 44 months, with a mean value of 11 months. RESULTS: Endovascular procedures demonstrated significant advantages with respect to reduced blood loss (408 versus 1287 ml), use of an intensive care unit (0.1 versus 1.75 days), length of hospitalization (3.9 versus 10.3 days), and quicker recovery (11 versus 47 days). Although the total number of postoperative complications was identical for the two groups, the nature of the complications differed considerably. Local and vascular complications characteristic of endovascular repair could frequently be corrected at the time of the procedure and tended to be less severe than systemic or remote complications, which predominated among the open surgical repair group. On an intent-to-treat basis, 23 (77%) of the 30 AAAs were successfully managed with endoluminal repair. The seven (23%) failures were attributable to two immediate conversions caused by access problems, three persistent endoleaks, one late conversion caused by AAA expansion, and one late rupture. CONCLUSIONS: Although less definitive than those for conventional operations, these early results suggest that endovascular AAA repair offers considerable benefits for appropriate patients. The results justify continued application of this method of AAA repair, particularly in the treatment of older persons at high risk.     

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group

Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients. A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002). The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities. Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system.