The coagulation cascade enzymes thrombin and factor Xa are known to have specificity pockets very similar to those of trypsin and plasmin. However, comparative molecular modeling analysis of the crystal structures of benzamidine-thrombin and benzamidine-trypsin, in conjunction with a docking analysis of 5-amidinoindole and related inhibitors in both enzymes reveals subtle differences between the specificity sites of the two types of enzymes. Specifically, thrombin and factor Xa, which have an alanine residue at position 190, exhibit increased activities for the rigid and more bulky bicyclic derivatives of benzamidine (e.g. amidinobenzofuran, amidinothiophene and amidinoindole), because of additional hydrophobic and H-bond interactions between the inhibitors and the specificity sites, whereas enzymes with a serine residue at position 190, like trypsin and plasmin, exhibit little difference in activity among the same set of compounds because of the orientational restriction imposed on the inhibitors by Ser190, which forms an additional H-bond with the amidino group of the inhibitors. Enzymes of both groups show similar responses to the flexible aminobenzamidine since the smaller size and the rotatable anilino group of the inhibitor would allow the inhibitor to achieve favorable electrostatic interactions with both groups of enzymes. 5-amidinoindole is the most dramatic example of the rigid bicyclic type inhibitor. Based on our docking analysis, we propose that a selective H-bond with the hydroxyl group of the catalytic Ser195 and the subtle differences in steric fit imposed by Ala/Ser at position 190 explain the high potency and selectivity of 5-amidinoindole for thrombin and factor Xa.

Amino Acid Substitution↗

PubMedDate not supplied

Distal upper extremity function following proximal humeral resection and reconstruction for tumors: contralateral comparison.

BACKGROUND: Most functional analyses after limb salvage operations about the shoulder have focused on proximal function with the assumption that distal function is largely unaffected. This analysis examines distal function objectively. METHODS: Objective laboratory data regarding distal upper extremity strength after reconstructive procedures for tumors near the shoulder joint was collected over a 16-year period. Thirty-two patients were able to participate fully in the data collection at an average most recent follow-up duration of > 3.5 years. RESULTS: Statistically significant reductions on the involved side compared with the uninvolved side in grip, forearm pronation, forearm supination, elbow flexion, and elbow extension strength were documented (p < 0.05). The magnitude of reduction in strength diminishes distally, with the greatest effect in this group of patients being observed in elbow extension, followed by elbow flexion, forearm supination, and forearm pronation. Grip strength consistently showed the least amount of strength reduction compared with the uninvolved side, even within resection and reconstruction groups. Subjective patient rating of dexterity was no less than 3 of 5. Ninety percent of patients rated their dexterity 4 of 5 (52%) or 5 of 5 (38%). CONCLUSIONS: Despite the insistence of "normal" function in the distal upper extremity after limb salvage procedures, complete normality is not maintained. However, the degree of maintenance of distal function appears to be high, especially for grip strength and forearm pronation strength, and patient satisfaction is acceptable.

Adolescent↗

PubMedDate not supplied

Depot medroxyprogesterone. Management of side-effects commonly associated with its contraceptive use.

Depot medroxyprogesterone acetate is one of the most popular, effective methods of contraception used in the United States. Many women experience unpleasant side effects from this method, including episodic vaginal bleeding, hair loss, depression, and weight gain. This Clinical Practice Exchange describes the treatment strategies for these side-effects used by nurse-midwives from a variety of settings and locales. Contraceptive use can be more acceptable for many women if they are better able to cope with unpleasant side effects of the method. This Clinical Practice Exchange provides knowledge to enhance client coping.

Adaptation, Psychological↗

PubMedDate not supplied

Functional comparison of pronation and supination strengths.

Studies have shown that functional activities involving pronation and supination, such as turning a doorknob or a screwdriver, involve wrist positions of extension and/or ulnar deviation. Previous studies of isometric forearm pronation and supination strength have utilized a neutral wrist position, resulting in a possible underestimation of true functional strength. Twenty healthy subjects between the ages of 24 and 45 years were assessed for isometric pronation and supination strength using cylinder, screwdriver, and doorknob handle adaptations. Maximal strength in both pronation and supination was observed with the use of the doorknob handle. Although pronation strength was exceeded by supination strength within all three handle adaptations, the difference was statistically significant for the screwdriver and doorknob handles. The results suggest that in clinical and research-oriented testing of maximal forearm rotation strength, further consideration must be given to the terminal grip device and positioning of the wrist.

Adult↗

PubMedDate not supplied

A mass spectrometry screening method for antiaggregatory activity of proteins covalently modified by combinatorial library members: application to sickle hemoglobin.

A homogeneous assay, based on electrospray mass spectrometry, is described for identifying compounds in a combinatorial library that covalently modify a protein and thereby enhance its solubility. The technique is based on measuring the distribution of modified proteins in the supernatant versus aggregate. Compounds having the greatest anti-aggregatory activity are those with the highest supernatant/aggregate ratio. Mass is used as a marker to identify which covalent modifier in the library is involved. An exploratory study is presented which demonstrates that the antisickling activity of a family of isothiocyanates, as measured by the standard C(sat) assay, correlates well (r(2) = 0.98) with the mass spectrometry analysis of the supernatant/aggregate distribution. The technique has potential for screening libraries capable of covalently modifying other proteins of clinical interest, e.g., Alzheimer's, Huntington's, and various prion related diseases.

Antisickling Agents↗

PubMedDate not supplied

Neurotoxicity of spinal procaine--a caution.

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Anesthesia, Spinal↗

PubMedDate not supplied

The practices of expert psychiatric nurses: accompanying the patient to a calmer personal space.

The focus of the care of potentially aggressive psychiatric patients has been on the use of seclusion and restraints. Recent concerns, however, about the potential for patient injury have made it imperative that nurses use alternative methods to calm patients who are escalating. Little is known about how expert nurses de-escalate the escalating patient. The purpose of this interpretive phenomenological study was to uncover and describe the knowledge embedded in the stories of psychiatric nurses who are skilled in the practices of de-escalating an escalating patient. Twenty registered nurses were interviewed using an unstructured format. The analysis of the data revealed that these nurses were skilled at noticing the patient, reading the situation and the patient, knowing where the patient was on the continuum, understanding the meaning of the behavior, knowing what the patient needed, connecting with the patient, and matching the intervention with the patient's needs.

Adolescent↗

PubMedDate not supplied

Being restrained: a study of power and powerlessness.

Previous research about the use of restraints has mainly sought generalizations regarding (a) who is likely to be restrained, (b) the frequency of the use of restraints, and (c) the behavior that precipitates the application of restraining devices. Therefore, there has been a paucity of research that attempts to understand the impact of restraint on the restrained person. The purpose of this study was to understand the meaning of the experience of being restrained for 10 psychiatric patients who had been restrained in leather restraints. Participants were interviewed in unstructured interviews. The taped interviews were transcribed and analyzed by means of a modification of an eight-stage interpretive process, grounded in Heideggerian phenomenology. In this article the theme of power is reported and discussed.

Adult↗

PubMedDate not supplied

Divergent origins and concerted expansion of two segmental duplications on chromosome 16.

An unexpected finding of the human genome was the large fraction of the genome organized as blocks of interspersed duplicated sequence. We provide a comparative and phylogenetic analysis of a highly duplicated region of 16p12.2, which is composed of at least four different segmental duplications spanning in excess of 160 kb. We contrast the dispersal of two different segmental duplications (LCR16a and LCR16u). LCR16a, a 20 kb low-copy repeat sequence A from chromosome 16, was shown previously to contain a rapidly evolving novel hominoid gene family (morpheus) that had expanded within the last 10 million years of great ape/human evolution. We compare the dispersal of this genomic segment with a second adjacent duplication called LCR16u. The duplication contains a second putative gene family (KIAA0220/SMG1) that is represented approximately eight times within the human genome. A high degree of sequence identity (approximately 98%) was observed among the various copies of LCR16u. Comparative analyses with Old World monkey species show that LCR16a and LCR16u originated from two distinct ancestral loci. Within the human genome, at least 70% of the LCR16u copies were duplicated in concert with the LCR16a duplication. In contrast, only 30% of the chimpanzee loci show an association between LCR16a and LCR16u duplications. The data suggest that the two copies of genomic sequence were brought together during the chimpanzee/human divergence and were subsequently duplicated as a larger cassette specifically within the human lineage. The evolutionary history of these two chromosome-specific duplications supports a model of rapid expansion and evolutionary turnover among the genomes of man and the great apes.

Animals↗

PubMedDate not supplied

The inheritance of frosted points in Nigerian Dwarf goats.

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Animal Diseases↗

PubMedDate not supplied

A retrospective study of prosthetic capsule technique for the treatment of problem cases of dislocated hips.

This article describes a technique for stabilizing coxofemoral luxations in dogs that uses placement of nonabsorbable sutures from two screws in the dorsal acetabular rim to a screw in the trochanteric fossa of the femur to create a prosthetic capsule. Twenty-one hips with luxations that were either recurrent or greater than 7 days duration were treated. Owners of 17 dogs were contacted from 4 to 40 months after surgery. Eight dogs were reported as having excellent function, three had good function, three had fair function, and three had poor function. No complications directly related to the technique were reported.

Animals↗

PubMedDate not supplied

Age-related changes in normal isometric shoulder strength.

Normative data are useful for assessing isometric shoulder strength in patients with bilateral shoulder abnormalities. The purpose of this study was to develop a normative database for shoulder strength in the clinically relevant positions and movements. Twenty combinations of exertions and postures-including flexion, extension, abduction, adduction, internal rotation, and external rotation-were tested for both the dominant and nondominant sides. Strength was measured isometrically using a modified Cybex II dynamometer. The cross-sectional study design included 120 subjects (60 women and 60 men) ranging in age from 20 to 78 years from southern Minnesota. Tables of normative strength data were constructed. Multivariate analyses were performed to assess the effect of age, sex, and weight on strength. Age was negatively associated with all strength measures, and weight was positively associated with them. Men were stronger than women when controlling for age and weight. Statistically significant differences between dominant and nondominant shoulders were found for only some of the strength measures taken. These normal data will be useful to the clinician, as they permit a standard against which to compare shoulder strength.

Adult↗