Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991

BACKGROUND: Data are limited regarding the classification and prognosis of patients with congestive heart failure (CHF) in the community. METHODS AND RESULTS: Using the resources of the Rochester Epidemiology Project, we evaluated all patients receiving a first diagnosis of CHF in Olmsted County, Minnesota, in 1991 (n=216). Among these patients, 88% were >/=65 years and 49% were >/=80 years of age. The prognosis of patients with a new diagnosis of CHF was poor; survival was 86+/-2% at 3 months, 76+/-3% at 1 year, and 35+/-3% at 5 years. Of the 216 patients, 137 (63%) had an assessment of ejection fraction. In these patients, systolic function was preserved (ejection fraction >/=50%) in 59 (43%) and reduced (ejection fraction <50%) in 78 (57%). Survival adjusted for age, sex, NYHA class, and coronary artery disease was not significantly different between patients with preserved and those with reduced systolic function (relative risk, 0.80; P=0.369). ACE inhibitors were used in only 44% of the total population with CHF. CONCLUSIONS: The present study reports the clinical characteristics and natural history of CHF as it presents in the community in the vasodilator era. CHF is a disease of the "very elderly," frequently occurs in the setting of normal ejection fraction, and has a poor prognosis, regardless of the level of systolic function. Diagnostic and therapeutic methods are underused in the community.     

Study of dosimetry consistency for kilovoltage x-ray beams

In this paper, the consistency of kilovoltage (tube potentials between 40 and 300 kV) x-ray beam dosimetry using the "in-air" method and the in-phantom measurement has been studied. The procedures for the measurement of the central-axis depth-dose curve, which serve as a link between the dose at the reference depth to the dose elsewhere in a phantom, were examined. The uncertainties on the measured dose distributions were analyzed with the emphasis on the surface dose measurement. The Monte Carlo method was used to calculate the perturbation correction factors for a photon diode and a NACP plane-parallel ionization chamber at different depths in a water phantom irradiated by 100-300 kV (2.43 mm Al-3.67 mm Cu half-value layer) x-ray beams. The depth-dose curves measured with these two detectors, after correcting for the perturbation effect (up to 15% corrections), agreed with each other to within 1.5%. Comparisons of the doses at the phantom surface and at 2 cm depth in water for photon beams of 100-300 kV tube potential obtained using the "backscatter" method and those using the "in-phantom" measurement have shown that the "in-air" method can be equally applied to this energy range if the depth-dose curve can be measured accurately. To this end, measured depth ionization curves require depth-dependent correction factors.     

Variations in adductor spasmodic dysphonia: acoustic evidence

The development of a validated primate model of progressive parkinsonism is a critical step in the evaluation of drugs that might halt or slow progression of Parkinson's disease. In this pilot study, we gradually exposed 14 cynomolgus monkeys to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), at a weekly dose of 0.5 mg/kg s.c. for 10 weeks, to determine their probability of not reaching a predetermined endpoint on a disability scale by Kaplan-Meier analysis. Four other MPTP-exposed animals were coadministered the potent free radical scavenger 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetylamino-2,2,4,6- tetramethylindan (OPC-14117) as a single oral daily dose of 0.6 g/kg, starting 2 weeks before MPTP initiation. The risk of reaching endpoint by week 10 was 79% and mean time before reaching endpoint was 6 weeks. Global motor activity, recorded in a subset of animals using a portable activity monitor, declined following the first MPTP dose and never recovered. Several cerebrospinal fluid indices of central monoamine metabolism collected by suboccipital puncture at 0, 5, and 10 weeks, including HVA, DOPAC, and tetrahydrobiopterin but not MHPG, were found to be "trait" markers for MPTP exposure, whereas CSF DOPAC and tetrahydrobiopterin constituted potential "state" markers for reaching endpoint. The antioxidant OPC-14117 did not protect against MPTP-induced parkinsonism. Further attempts to validate this incremental model of neurotoxin-induced parkinsonism as a predictor of patient responses to putative neuroprotective agents appear warranted.     

Comparison of 51Cr-EDTA with 99m-Tc-DTPA slope clearance for estimation of glomerular filtration rate using the one compartment model

AIM: Of this study is to determine the relationship between 51Cr-EDTA and 99mTc-DTPA slope clearance applying the "one-compartment model". METHODS: The "one-compartment model" was chosen to calculate and to compare the glomerular filtration rates of 25 patients with normal and pathological creatinin values after injection of 51Cr-EDTA and 99mTc-DTPA simultaneously. RESULTS: The two clearance values correlated well (r = 0.996), and the 99mTc-DTPA clearance was systematically higher (28%). The 99mTc-DTPA was calculated and compared after taking three plasma samples. Taking two samples, only minor differences were seen and the correlation was high (r = 0.992). CONCLUSION: The results of this study encouraged us to adopt the use of 99mTc-DTPA instead of 51Cr-EDTA in determining the glomerular filtration applying the "one-compartment model" in slope with two plasma samples.     

Ventral subiculum regulates hypothalamo-pituitary-adrenocortical and behavioural responses to cognitive stressors

The high resolution crystal structure of Saccharomyces cerevisiae phosphoglycerate mutase has been determined. This structure shows important differences from the lower resolution structure deposited in 1982. The crystal used to determine the new structure was of a different form, having spacegroup P2(1). The model was refined to a crystallographic R-factor of 18.9% and a free R-factor of 28.4% using all data between 25 and 2.3 A and employing a bulk solvent correction. The enzyme is a tetramer of identical, 246 amino acid subunits, whose structure is revealed to be a dimer of dimers, with four independent active sites located well away from the subunit contacts. Each subunit contains two domains, the larger with a typical nucleotide binding fold, although phosphoglycerate mutase has no physiological requirement to bind nucleotides. The catalytic-site histidine residues are no longer in a "clapping-hands" conformation, but more resemble the conformation seen in the distantly related enzymes prostatic acid phosphatase and fructose-2,6-bisphosphatase. However, the catalytic histidine residues in the mutase are found to be much closer to each other than in the phosphatase structures, perhaps due to the absence of bound ligands in the mutase crystal. An intricate web of H-bonds is found around the catalytic histidine residues, high-lighting residues probably important for maintaining their correct orientation and charge. The positions of certain other residues, including some found near the catalytic site and some lining the catalytic-site cleft, have been changed by the correction of registration errors between sequence and electron density in the original structure. Electron density was apparent for a portion of the functionally important C-terminal tail, which was absent from the earlier structure, showing it to adopt a mainly helical conformation.     

Estimating risk associated with care in alternative settings: deterioration among children hospitalized

The incidence of ductal carcinoma in situ (DCIS) has increased with the widespread use of screening mammography. DCIS is often suspected when clustered microcalcifications are evidenced on routinely performed mammography. High quality mammographies are required and should be completed with magnification views. Mammographic--pathologic correlations are described according to the new classifications as well as unusual forms of presentation on mammography. Early contrast enhancement in DCIS on dynamic MRI is reported and seems to be related with angiogenesis. A wire localization procedure of non-palpable lesions has to be performed and per-operative specimen radiography is mandatory. Stereotaxic large core needle biopsy is a valuable alternative to surgical biopsy but a multidisciplinary team approach is necessary and follow-up is recommended if no excisional biopsy is done. Quality in the management of DCIS depends on the coherence of the "multidisciplinary team".     

Oxyanion-mediated inhibition of serine proteases

Novel aryl derivatives of benzamidine were synthesized and tested for their inhibitory potency against bovine trypsin, rat skin tryptase, human recombinant granzyme A, human thrombin, and human plasma kallikrein. All compounds show competitive inhibition against these proteases with Ki values in the micromolar range. X-ray structures were determined to 1.8 A resolution for trypsin complexed with two of the para-substituted benzamidine derivatives, 1-(4-amidinophenyl)-3-(4-chlorophenyl)urea (ACPU) and 1-(4-amidinophenyl)-3-(4-phenoxyphenyl)urea (APPU). Although the inhibitors do not engage in direct and specific interactions outside the S1 pocket, they do form intimate indirect contacts with the active site of trypsin. The inhibitors are linked to the enzyme by a sulfate ion that forms an intricate network of three-centered hydrogen bonds. Comparison of these structures with other serine protease structures with noncovalently bound oxyanions reveals a pair of highly conserved oxyanion-binding sites in the active site. The positions of noncovalently bound oxyanions, such as the oxygen atoms of sulfate, are distinct from the positions of covalent oxyanions of tetrahedral intermediates. Noncovalent oxyanion positions are outside the "oxyanion hole." Kinetics data suggest that protonation stabilizes the ternary inhibitor/oxyanion/protease complex. In sum, both cations and anions can mediate Ki. Cation mediation of potency of competitive inhibitors of serine proteases was previously reported by Stroud and co-workers [Katz, B. A., Clark, J. M., Finer-Moore, J. S., Jenkins, T. E., Johnson, C. R., Ross, M. J., Luong, C., Moore, W. R., and Stroud, R. M. (1998) Nature 391, 608-612].     

Loss of shaker K channel conductance in 0 K+ solutions: role of the voltage sensor

In potassium-free solutions some types of K channels enter a long-lasting nonconducting or "defunct" state. It is known that Shaker K channels must open in K+-free solutions to become defunct. Gating current studies presented here indicate an abnormal conformation in the defunct state that restricts S4 movement and alters its kinetics. Thus an abnormality initiated in the P region spreads to the gating apparatus. We find that channels most readily become defunct on repolarization to an intermediate voltage, thus prolonging occupancy of one of the several intermediate closed states. The state dependence of becoming defunct was further dissected by using the gating mutant L382A. Simply closing this channel at 0 mV (reversing the last activation step) does not make the mutant channel defunct. Instead, it is necessary to move further left (more fully closed) in the activation sequence. This was confirmed with ShIR experiments showing that channels become defunct only if there is inward gating charge movement. Rapid transit through the intermediate states, achieved at very negative voltage, is relatively ineffective at making channels defunct. Several mutations that removed C-type inactivation also made the channels resistant to becoming defunct. Our results show that normal gating current cannot be stably recorded in the absence of K+.     

Non-uniform sampling strategies for digital control

Most conventional control algorithms cause numerical problems where data is collected at sampling rates that are substantially higher than the dynamics of the equivalent continuous-time operation that is being implemented. This is of relevant interest in applications of digital control, in which high sample rates are routinely dictated by the system stability requirements rather than the signal processing needs. Digital control systems exhibit bandwidth limitations enforced by their closed-loop frequency requirements that demand very high sample rates. Considerable recent progress in reducing sample frequency requirements has been made through the use of non-uniform sampling schemes, so called alias-free signal processing. The approach prompts the simplification of complex systems and consequently enhances the numerical conditioning of the implementation algorithms that otherwise would require very high uniform sample rates. However, the control communities have not yet investigated the use of intentional non-uniform sampling. The purpose of this article is to address some algorithmic issues when using such regimes for digital control.     

Stabilization of gas cavitation nuclei by surface-active compounds

Gas bubbles are the primary agent in producing the pathogenic effects of decompression sickness. Numerous experiments indicate that bubbles originate in water, and probably also in man, as pre-existing gas nuclei. This is surprising considering that gas phases larger than 1 micron should rise to the surface of a standing liquid, whereas smaller ones should dissolve rapidly due to surface tension. Several stabilizing mechanisms have been suggested, and each has been refuted on experimental grounds. In this article, we propose a new model that arises out of a systematic study of the earlier theories. We review these theories and conclude that gas cavitation nuclei must be held intact by surface-active skins that are initially permeable. The first quantitative analysis of bubble formation data from supersaturated gelatin is summarized and leads to the further conclusion that skins can become impermeable if the ambient pressure is increased rapidly by a sufficient amount. Our model owes much to Sirotyuk, who "demonstrated experimentally that stabilization of gas bubbles acting as cavitation nuclei in water is always attributable to the presence of surface-active substances in the water".