Cuff-occluded rate of rise of peripheral venous pressure: a new, highly sensitive technique for monitoring blood volume status during hemorrhage and resuscitation.

We investigated the cuff-occluded rate of rise of peripheral venous pressure (CORRP)--a new, nearly noninvasive peripheral hemodynamic monitoring parameter--in dogs subjected to hemorrhage and resuscitation. Twelve adult mongrel dogs under general anesthesia were subjected to hemorrhage of 30% of their estimated total blood volume (TBV) for 30 minutes; after this time the extracted blood was reinfused. Arterial pressure (AP), central venous pressure (CVP), pulmonary arterial pressure (PAP), cardiac output (CO), pulmonary venous pressure (PWP), heart rate, and CORRP were continuously monitored. A "clinically significant change" (CSC) in CORRP and CO was defined as a change that exceeded two standard deviations from the mean of five baseline measurements made before the onset of hemorrhage, whereas a CSC in PWP or CVP was conservatively defined as a change that exceeded 2 mm Hg from the average of five baseline measurements, and a CSC in PAP and AP was defined as a change that exceeded 3 mm Hg and 5 mm Hg, respectively from the average of the baseline measurements. There was no consistent change in heart rate during hemorrhage. Thus defined, a CSC in CORRP occurred after an average extraction of 9.2% +/- 4.7% TBV, whereas a CSC was not seen until an average loss of 16.5% +/- 8.1% TBV for AP, 21% +/- 13% TBV for PWP, 15.5% +/- 7% TBV for PAP, and 35% +/- 3% TBV for CVP. These average blood losses are all significantly different from the average blood loss required to effect a CSC in CORRP. The blood loss required to effect a CSC in CO averaged 9.7% +/- 6%. We conclude that in these anesthetized dogs, CORRP detected blood loss earlier than other commonly used hemodynamic parameters, including several invasive parameters such as CVP, PAP, and PWP; CORRP and CO were equivalent in their ability to detect early stages of blood loss.

Methods for onset detection of voluntary motor responses in tremor patients.

Accurate onset detection of the voluntary response is a prerequisite in reaction time studies when used in investigations on human motor control. The detection algorithm required performs a transformation of the continuous physical signal (e.g., force, movement) containing the response into a discrete event from which the reaction time (RT) is derived. Therefore, RT always comprises both the cognitive and/or motor delay component imaging the duration of the initiation process conducted by the sensorimotor system and, in addition, some spurious delay caused by the detection algorithm. As a standard method, onset detection is realized by the measurement device itself (e.g., the release of a micro switch) by defining the response onset as the point where the observed signal passes a certain threshold. Thus, weak and abnormal response profiles which are typical for a variety of central motor disorders (e.g., Parkinson's disease) may introduce high RT variability as well as systematic errors. The aim of this study was to improve accuracy of onset detection by application of an appropriate filter to the measured signal before entering the final decision stage. Three algorithms (lowpass differentiator, inverse filter, linear autoregressive (AR) predictor) were implemented and tested on simulated and real data under both on-line and off-line conditions with special interest to the influence of quasi-periodic background activity like tremor. It is shown that a significant improvement in onset detection accuracy, compared with the simple switch, can be achieved by using appropriate low order adaptive filters with the AR-predictor being the most efficient solution.

Localized intestinal perforation following intravenous indomethacin in premature infants.

This is a case report of focal intestinal perforation in a premature neonate following intravenous administration of indomethacin for patent ductus arteriosus.

X-ray investigations of sulfur-containing fungicides. III. Intramolecular forces governing the conformation of a novel orthorhombic polymorph of benzoylmethyl phenyl sulfone, benzoylmethyl 4-chlorophenyl sulfone and benzoylphenylmethyl phenyl sulfone.

The crystal and molecular structures of three beta-ketosulfones: benzoylmethyl phenyl sulfone (I), benzoylmethyl 4-chlorophenyl sulfone (II) and benzoylphenylmethyl phenyl sulfone (III) have been investigated using X-ray analysis and quantum mechanics ab initio calculations. Compound (I) crystallizes in the monoclinic and orthorhombic crystal systems. The crystal structure of the orthorhombic polymorph has not been reported previously. At room temperature and in the presence of daylight the pale yellow orthorhombic crystals undergo transformation to the stable colourless monoclinic polymorph. Hyperconjugative sigma(S-C1) - pi(*)(C2=O3) and sigma(*)(S-C1) - pi(C2=O3) stabilization energies in benzoylmethyl phenyl sulfones are highly dependent on the central dihedral angle alpha: S-C1-C2=O3 and are largest for a gauche arrangement, as found in both crystal forms of (I). The electron density distribution in all compounds (I), (II) and (III) is significantly affected by interactions of oxygen lone pairs with non-bonding orbitals of the adjacent S-C1 and C1-C2 bonds. The latter effect is responsible for back-donation of the electron density from O atoms towards the central part of the molecule.

1,2-Diphenyl-2-(phenyldiazenyl)-2-tosylethanone, an example of a fungicide containing a sulfonyl group.

The molecule of the title compound, C(27)H(22)N(2)O(3)S, adopts an irregular propeller shape with the tetrahedral C1 atom pivotal. The alpha-azophenyl and alpha-phenyl moieties are approximately coplanar. Electrostatic attraction of the oppositely charged atoms generates several short intramolecular contacts involving the sulfonyl, azo and carbonyl groups. Characteristic bond-length distribution of the central part of the molecule indicates that the Coulombic charge transfer is supplemented by hyperconjugation involving donation of electron density from the azo moiety towards the sulfonyl and carbonyl groups.

X-ray investigations of sulfur-containing fungicides. IV. 4'-[[Benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide.

The conformations of the two approximately isomorphous structures 4'-[[benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide, C(22)H(18)ClN(3)O(4)S, and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide, C(23)H(21)N(3)O(5)S, are stabilized by resonance-assisted intramolecular hydrogen bonds linking the hydrazone moieties and sulfonyl groups. The stronger bond is observed in the former compound. The difference in electronic properties between the Cl atom and the methoxy group is too small to significantly alter the non-bonding interactions of the sulfonyl and beta-carbonyl groups.

The stereochemistry of the phosphorus-selenium bond. VII. Structure of 5,5-dimethyl-2-(o-nitrophenyl)amino-1,3,2-dioxaphosphorinane 2-selenide.

C11H15N2O4PSe, Mr = 349.2, monoclinic, P2(1)/c, a = 10.204(3), b = 19.891 (3), c = 6.823 (3) A, beta = 94.41 (3) degrees, U = 1380.8 A3, Z = 4, Dm = 1.66, Dx = 1.68 Mg m-3, Mo K alpha, lambda = 0.71069 A, mu = 3.05 mm-1, F(000) = 704, room temperature, R = 0.026 for 1755 observed reflections [I greater than 3 sigma (I)]. The dioxaphosphorinane ring adopts a flattened chair conformation with P = Se and P-N bonds in equatorial and axial positions respectively. The properties of the molecule are mainly governed by anomeric interactions between endocyclic oxygen lone pairs and antibonding orbitals of the axial P-N bond.

Crystal structure of calcium-free proteinase K at 1.5-A resolution.

Proteinase K from the fungus Tritirachium album Limber binds two Ca2+ ions, one strongly (Ca 1) and the other weakly (Ca 2). Removal of these cations reduces the stability of proteinase K as shown by thermal denaturation, but the proteolytic activity is unchanged. The x-ray structures of native and Ca(2+)-free proteinase K at 1.5-A resolution show that there are no cuts in the polypeptide backbone (i.e. no autolysis), Ca 1 has been replaced by Na+, while Ca 2 has been substituted by a water associated with a larger but locally confined structural change at that site. A small but concerted geometrical shift is transmitted from the Ca 1 site via eight secondary structure elements to the substrate recognition site (Gly100-Tyr104, and Ser132-Gly136) but not to the catalytic triad (Asp39,His69,Ser224). This is accompanied by positional changes of localized waters.

Simulations of nucleation and early growth stages of protein crystals.

Analysis of known protein crystal structures reveals that interaction energies between monomer pairs alone are not sufficient to overcome entropy loss related to fixing monomers in the crystal lattice. Interactions with several neighbors in the crystal are required for stabilization of monomers in the lattice. A microscopic model of nucleation and early growth stages of protein crystals, based on the above observations, is presented. Anisotropy of protein molecules is taken into account by assigning free energies of association (proportional to the buried surface area) to individual monomer-monomer contacts in the lattice. Lattice simulations of the tetragonal lysozyme crystal based on the model correctly reproduce structural features of the movement of dislocation on the (110) crystal face. The dislocation shifts with the speed equal to the one determined experimentally if the geometric probability of correct orientation is set to 10(-5), in agreement with previously published estimates. At this value of orientational probability, the first nuclei, the critical size of which for lysozyme is four monomers, appear in 1 ml of supersaturated solution on a time scale of microseconds. Formation of the ordered phase proceeds through the growth of nuclei (rather then their association) and requires nucleations on the surface at certain stages.

Alpha-hydroxymethylserine as a peptide building block: synthetic and structural aspects.

A synthetic methodology has been developed for peptide bond formation with alpha-hydroxmethylserine as the carboxyl or amino component and also for the preparation of homo-sequences. The key intermediate, O,O-protected alpha-hydroxymethylserine in the form of an isopropylidene derivative, is easily accessible and represents the first example of a heterocyclic C(alpha,alpha)-disubstituted amino acid containing an 1,3-dioxane ring. The use of this intermediate facilitates protection of the sterically hindered amino and carboxyl groups and is advantageous for the coupling and deprotection steps. X-ray structure determination of Z-HmS(Ipr)-Ala-OMe revealed that the two crystallographically independent molecules present in the asymmetric unit adopt an S-shaped conformation. In the one molecule the achiral HmS(Ipr) residue has the torsion angle values (phi = 61.4 degrees, psi, = 40.8 degrees) in the left-handed helical region of the Ramachandran map, while in the second molecule the negative torsion angles (phi = -60.1 degrees, psi = -44.4 degrees) are associated with the right-handed helix.

Laparoscopy in morbidly obese patients.

STUDY OBJECTIVE: To assess the safety and efficacy of different insufflation methods in morbidly obese women undergoing laparoscopy. DESIGN: Retrospective analysis of 13 years' experience (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred thirty-eight morbidly obese women (weight >250 lbs, body mass index >36). The heaviest patient weighed 400 lbs and had a body mass index of 66. INTERVENTION: Laparoscopic tubal sterilizations and diagnostic laparoscopies performed on an outpatient basis by residents under faculty supervision. MEASUREMENTS AND MAIN RESULTS: Of 138 patients, 36 underwent standard transumbilical insufflation with 5 failures, 83 had transuterine insufflation with 3 failures, 12 had subcostal insufflation with 1 failure, and 7 had open laparoscopy with 2 failures. CONCLUSION: The insufflation failure rate was significantly high for transumbilical insufflation and open laparoscopy, and not for transuterine or subcostal insufflation. Morbid obesity was not a contraindication to laparoscopy. (J Am Assoc Gynecol Laparosc 6(3):307-312, 1999)

Technical limitations in the rapid infusion of intravenous fluids.

We compared fluid delivery, both in vitro and in vivo, using various combinations of fluid sets and intravenous catheters. Administration sets were a minidrip, a maxidrip, and a blood infusion set. The catheters included 14-, 16-, 18-, and 20-gauge short catheters, 16- and 19-gauge long catheters, and an 8 French catheter introducer for flow-directed pulmonary arterial lines. Blood infusion tubing alone delivered fluid at 3.12 +/- .07 mL/second, significantly faster than either the maxidrip (2.59 +/- .06, P less than .01) or the minidrip (0.56 +/- .02, P less than .001). The 8 French introducer provided no additional resistance to the flow of the maxidrip or blood infusion set when used in combination with an anesthesia extension. All the other catheters slowed flow significantly. Percutaneous insertion of an 8 French catheter introducer connected to blood administration tubing allows for rapid delivery of fluids and for subsequent insertion of a Swan-Ganz catheter, which is often necessary in critically ill patients.

Inhibition of proteinase K by methoxysuccinyl-Ala-Ala-Pro-Ala-chloromethyl ketone. An x-ray study at 2.2-A resolution.

The crystal structure of the transition state analog complex formed covalently between proteinase K and methoxysuccinyl-Ala-Ala-Pro-Ala-chloromethyl ketone was determined by x-ray diffraction methods at a resolution of 2.2 A and refined by constrained least squares to an R factor of 19.8% for the 11864 structure amplitudes greater than 1 sigma F. The chloromethyl ketone group is covalently linked with the active site functional groups His69(N epsilon) and Ser224(O gamma). The former has substituted for chlorine and the latter has attacked the carbon of the ketone group, thereby forming the tetrahedral carbon atom of the transition state analog. The peptide part of the inhibitor is in an extended conformation and fills subsites S1 to S5 of the substrate recognition site. Its backbone hydrogens bond with strands 100-104 and 132-136 of the substrate recognition site as the central strand of a three-stranded antiparallel beta-pleated sheet. This sheet formation is associated with a movement by approximately 1 A of strand 100-104 which is probably associated with the insertion of the bulky proline side chain. The methoxysuccinyl group is stacked on the phenolic side chain of Tyr104 that is a part of the bottom of the recognition site. Biochemical studies show that shorter inhibitors of this type are less effective than the longer one, because there are fewer hydrogen bonding and van der Waals/stacking interactions.