Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm

BACKGROUND: Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. METHODS AND RESULTS: In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow-up time of 3.2 years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI-1) activity at test, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA-ag at rest (P < .05), high PAI-1 activity (P < .05), and low TPA-ag responses to exercise (P < .05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA-ag levels and metoprolol treatment with a 2% increase (P < .001 for treatment difference). CONCLUSIONS: Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris.     

An experimental model of pleural cancer. Value of orthotopic implantation of human tumor tissue in nude mice

In a comparison article we report that maternal PO exposure to 2.5 mg/kg all-trans retinoic acid (RA) daily for 3 consecutive days over gestational days (GD) 11-13 produces a 10% reduction in weight of cerebellum at 4 weeks of age, not accompanied by other malformations. Here we report the results of a preliminary behavioral analysis of offspring exposed gestationally to RA as above. Exposed dams were allowed to deliver normally, and litters were culled to eight pups (4 +/- 1 of each sex) at birth. Both male and female offspring were tested prior to weaning on GD 21. Thereafter females were killed on postnatal day (PND) 28 for verification of RA effects on regional brain weight, and all subsequent behavioral testing was conducted on males. Preweaning tests were restricted to negative geotaxis (PND 8-9) and open field activity (PND 22). Postweaning tests included open field activity (PND 43), auditory startle response (three times, on PNDs 22, 43, and 84), 2-week activity in residential running wheels (PNDs 62-76), complex maze performance for 5 consecutive days (PND 83-87), emergence latency (PND 106), and assessment of the behavioral response to an amphetamine challenge (PND 107). Males were then killed on PND 108 for verification of RA effects on regional brain weights. In this study, RA reduced weight of cerebellum but not striatum. Cerebellar weight was 92% of control values in PND 28 females, and this weight difference had diminished to 95% of control weight by PND 108 in males. There were no treatment effects on negative geotaxis, activity in a small open field, auditory startle amplitude, or latency to enter an illuminated alley from a dark chamber. Maze learning occurred at levels equal to or slightly better than controls. Running wheel activity was enhanced by RA exposure, whereas activity in response to an amphetamine challenge was reduced by such exposure. We conclude that RA doses low enough to produce mild weight reductions in cerebellum, without attendant malformations, can alter behavior. The precise nature of these alterations remains to be elucidated, but the findings reported here suggest that effects may be more pronounced on activity than on learning.     

In vitro mutagenesis of PH-20 hyaluronidase from human sperm

The cDNA encoding PH-20 hyaluronidase from human sperm has been mutated at five positions by in vitro mutagenesis. We have changed three acidic amino acids and two arginine residues that are conserved in the sequence of mammalian PH-20 polypeptides as well as in the hyaluronidases from bee and hornet venom. Of the former, the mutants [Gln113]PH-20 and [Gln249]PH-20 had no detectable enzymatic activity; the mutant [Asn111]PH-20 had about 3% activity. The mutant [Thr252]PH-20 was also inactive, while [Gly176]PH-20 had only about 1% activity. This indicates that the PH-20 hyaluronidases, like numerous enzymes that hydrolyze glycosidic bonds, have acidic amino acids in their active site. Moreover, for the binding of the substrate, the polyanion hyaluronan, arginine residues appear to be essential.     

Linear crosstalk in 4×4 semiconductor optical amplifier gateswitch matrix

We report a comprehensive crosstalk investigation of a packaged InGaAsP/InP 4×4 semiconductor optical amplifier gate switch matrix, experimentally as well as theoretically. For a fully loaded switch with the same wavelength on all four inputs, all possible switching combinations are analyzed, thus yielding realistic crosstalk figures. Coherent and incoherent crosstalk phenomena are identified, and a switch crosstalk less than -40 dB has been measured     

Near Shannon limit performance of low density parity check codes

The authors report the empirical performance of Gallager's low density parity check codes on Gaussian channels. They show that performance substantially better than that of standard convolutional and concatenated codes can be achieved; indeed the performance is almost as close to the Shannon limit as that of turbo codes     

Mössbauer effect study of mechanically alloyed Γ and Γ1 Fe−Zn intermediate phases

The Mössbauer effect measurements of as-ball-milled mechanically alloyed Fe?Zn intermediate phases of Γ (Fe₃Zn₁₀) and Γ₁ (Fe₅Zn₂₁) compositions exhibit characteristic spectra consisting of triplets. Each is characterized with an Fe site with unusually large quadrupole splittings measuring 0.940 mm/s in the cubic Fe?Zn phases and, in addition, three other doublets. In the aged state, both compositions show spectra free of the Fe site with quadrupole splitting of 0.940 mm/s, designated as _MSΓFe₁ and _{MSΓ 1}Fe₁, respectively. This suggests that the metastable states are similar, while their separate transformation paths to stable equilibrium lead to distinct crystal structures. The parameters for the aged states are compared with those reported in the literature for both phases.     

Comparison of radiochemical purity control methods for 99Tcm radiopharmaceuticals used in hospital radiopharmacies

The free fraction of pertechnetate in 99Tcm radiopharmaceuticals has to be tested for quality control reasons in line with the European Pharmacopoeia. Such quality control is often performed by miniaturized chromatographic methods. There are several recommended methods in the literature for quality control of the same radiopharmaceuticals, though it is unlikely that all methods are equivalent. Some of these methods were compared, taking into account different parameters (spot size, time required, analytical artifacts, true separation and shape of the chromatographic peaks, ease of handling), to verify the best method for the control of each radiopharmaceutical. It would appear that instant thin layer chromatography silica gel is the best support for these miniaturized methods, using MEK as solvent to check DTPA, DMSA, gluconate, pyrophosphate, medronate and phytate; NaCl 20% solution is the best solvent for IDA derivatives, human albumin and albumin particles (microspheres, macroaggregates).     

Community life support training: does it attract the right people?

We first performed autogenous bone grafting for lesions of the hallux sesamoid in 1984. During the next 9 years, 21 patients (11 men and 10 women with an average age of 34 and 32 years, respectively) underwent this surgical procedure for symptomatic tibial hallux sesamoid non-unions. Successful bony union was achieved in all but two patients. The majority of patients obtained concomitant relief of preoperative symptomatology and returned to their preinjury level of activity. We believe that this procedure serves as an alternative to hallux sesamoid excision in selected cases.     

A genetic algorithm for multiple molecular sequence alignment

MOTIVATION: Multiple molecular sequence alignment is among the most important and most challenging tasks in computational biology. The currently used alignment techniques are characterized by great computational complexity, which prevents their wider use. This research is aimed at developing a new technique for efficient multiple sequence alignment. APPROACH: The new method is based on genetic algorithms. Genetic algorithms are stochastic approaches for efficient and robust searching. By converting biomolecular sequence alignment into a problem of searching for optimal or near-optimal points in an 'alignment space', a genetic algorithm can be used to find good alignments very efficiently. RESULTS: Experiments on real data sets have shown that the average computing time of this technique may be two or three orders lower than that of a technique based on pairwise dynamic programming, while the alignment qualities are very similar. AVAILABILITY: A C program on UNIX has been written to implement the technique. It is available on request from the authors.