Clinical experience with the percutaneous hemopump during high-risk coronary angioplasty

The percutaneous Hemopump showed beneficial effects during coronary angioplasty in 32 high-risk patients with unloading of the left ventricle during ischemia and maintaining cardiac output with mean aortic pressures of 50 mm Hg in case of cardiac arrest (3 patients). High procedure-related morbidity (occlusion of femoral artery in 2 patients; bleeding with need of transfusion in 4 patients) and mortality (4 of 32 patients) rates demonstrate the need for a very careful selection of patients.     

Feasibility of estimating glomerular filtration rate in children using single-sample adult technique

This work was undertaken to verify whether a single-sample adult technique, when applied using body surface-corrected plasma concentration, can be used in place of specific pediatric method to estimate 51Cr-EDTA renal clearance in children. METHODS: In a series of 90 children (aged 0.1 to 15 yr). 51Cr-EDTA renal clearance was calculated using for different approaches. The first approach used specific pediatric single-sample methods; three techniques were chosen and they all used 120-min plasma concentration. The second approach used the same three specific pediatric methods, but they were applied using 120-min plasma concentration prescaled for 1.73 m2 body surface area. The third approach used single-sample methods designed for adults; three methods were again chosen. They all used 240-min plasma concentration. The fourth approach used the same adults algorithms, but they were applied using 240-min plasma concentration prescaled for 1.73 m2 body surface area. RESULTS: Clearances calculated using the three specific pediatric methods were all closely cross-correlated regardless of whether or not the plasma concentration was prescaled. The use of classical adult methods produced in some cases obviously erroneous clearance values. Improvements were observed when the same adult methods were applied using prescaled plasma concentration. Nonetheless, the clearance values obtained only fairly correlated with those obtained using specific pediatric methods. CONCLUSION: The single-sample adult technique using plasma concentration prescaled for 1.73 m2 body surface area cannot be used in place of a specific pediatric single-sample method to estimate 51Cr-EDTA renal clearance in children.     

Simplified appendectomy without stump embedding. Experiences of 20 years conventional and 5 years laparoscopic application

Since 1975, the Department of Surgery in the Grevenbroich Community Hospital (Germany) has applied a simplified technique of open appendectomy. The inhouse modified procedure without stump embedding has been performed in 3,448 cases to date. The same approach has been used in 1,463 laparoscopic appendectomies since 1991. In the laparoscopic procedure the stump is ligated solely with Roeder's loop. None of the 4,911 patients who have undergone either open or laparoscopic appendectomy have developed stump inadequacy or stercoral fistulae. According to the special literature, the complication rate after appendectomies without stump embedding is lower than that after standard procedures. In retrospect, laparoscopic appendectomy with simple ligation has confirmed the results achieved with simple ligation in open appendectomies. The technique should therefore become more common practice in open appendectomies, as well.     

2-Azetidinone cholesterol absorption inhibitors: structure-activity relationships on the heterocyclic nucleus

A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((-)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure-activity relationships consistent with a well-defined molecular target. The details of these structure-activity relationships and their implications on the nature of the putative pharmacophore are discussed.     

New taxane diterpenoids from the roots of Taxus mairei

OBJECTIVE: We tested the hypothesis that nitric oxide synthesis by the kidney is increased in children with primary nephrotic syndrome. METHODS: We examined the urinary excretion of nitrite, a stable metabolite of nitric oxide, using the Griess reaction, in children with nephrotic syndrome. RESULTS: In comparison with healthy children, patients with minimal change nephrotic syndrome had increased urinary nitrite excretion regardless of whether the disease was in relapse or remission (p < 0.025). In contrast, urinary nitrite excretion was similar in control subjects and patients with focal segmental glomerulosclerosis or IgA nephropathy. CONCLUSION: These findings indicate that measurement of urinary nitrite excretion may be a useful test to help discriminate between minimal change nephrotic syndrome and focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome.     

Tyrosine administration prevents hypoxia-induced decrements in learning and memory

Exposure to hypobaric hypoxia rapidly produces decrements in learning and memory. Tyrosine, a neurotransmitter precursor, has beneficial behavioral effects when administered to animals and humans exposed to various acute stressors. To determine whether tyrosine would protect rats from the adverse effects of hypobaric hypoxia on spatial reference and working memory, it was administered to 27 male Fischer 344 rats tested in the Morris water maze. Rats were tested starting at 2 and 6 h of an 8 h exposure to a simulated altitude of 5950 m (19,500 ft) or sea level. Tyrosine or placebo was administered 1/2 h prior to each testing session (400 mg/kg, IP). Altitude exposure significantly increased working memory escape latency; treatment with tyrosine reversed this decrement. There was no effect of altitude or tyrosine on reference memory. There were also no treatment-related differences in performance when animals were tested the next day at sea level. The beneficial effects of tyrosine on working memory performance may be due to a direct effect of tyrosine on memory, alleviation of a hypoxia-induced retardation of learning, or to other central or peripheral effects of this dietary catecholamine precursor.     

Detection and recognition of radial frequency patterns

Detection thresholds for radial deformations of circular contours were measured using a range of radii and contour peak spatial frequencies. For radial frequencies above two cycles, thresholds were found to be a constant fraction of the mean radius across a four-octave range of pattern radii and peak spatial frequencies (mean Weber fraction: 0.003-0.004). At low radial frequencies, thresholds were unaffected by contrast reduction. In 167 ms presentations, subjects were able to identify radial frequencies of six cycles and below with an accuracy of over 90% correct even when phase was randomized. The extreme sensitivity of subjects to these radial deformations (as low as 2-4 s of arc) cannot be explained by local orientation or curvature analysis, and points instead to the global pooling of contour information at intermediate levels of form vision.     

Absolute conservation of residue 6 of immunoglobulin heavy chain variable regions of class IIA is required for correct folding

While studying the expression of single-chain antibodies (scFv) derived from several murine monoclonal antibodies, we found that residue 6 in Framework region 1 of the heavy chain variable domain plays a crucial role in antibody folding. Binding activity of three murine antibodies with a heavy chain variable region (VH) subgroup IIA was completely lost when at this position the wild-type residue glutamine (Q) was substituted by glutamate (E). Increased sensitivity towards trypsin digestion of soluble scFv suggested that the lack of binding activity was caused by incorrect folding of Q6E mutants. Grafting of the three additional class IA derived FR1 residues, based upon the comparison between both classes of VH sequences, on to the 'defect' subgroup IIA sequence, partially restored the antigen binding activity of the Q6E-containing scFv. Our results suggest that residue 6 of the heavy chain may be part of a folding nucleus, involving the first two beta-strands of Framework region 1. The evolutionary conservation of either glutamine or glutamate at position 6 in different antibody families may well indicate that within immunoglobulin VH domains, different family specific folding nuclei have evolved.     

Discovery and evaluation of a series of 3-acylindole imidazopyridine platelet-activating factor antagonists

Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N, N-dimethylcarbamoyl)-4-ethynyl-3-[3-fluoro-4-[(1H-2-methylimidazo[4,5-c] pyrid-1-yl)methyl]benzoyl]indole hydrochloride (ABT-491, 22 m.HCl) which has been evaluated extensively and is currently in clinical development.