Laminin promotes coagulation and thrombus formation in a factor XII-dependent manner.

BACKGROUND: Laminin is the most abundant non-collagenous protein in the basement membrane. Recent studies have shown that laminin supports platelet adhesion, activation and aggregation under flow conditions, highlighting a possible role for laminin in hemostasis. OBJECTIVE: To investigate the ability of laminin to promote coagulation and support thrombus formation under shear. RESULTS AND METHODS: Soluble laminin accelerated factor (F) XII activation in a purified system, and shortened the clotting time of recalcified plasma in a FXI- and FXII-dependent manner. Laminin promoted phosphatidylserine exposure on platelets and supported platelet adhesion and fibrin formation in recalcified blood under shear flow conditions. Fibrin formation in laminin-coated capillaries was abrogated by an antibody that interferes with FXI activation by activated FXII, or an antibody that blocks activated FXI activation of FIX. CONCLUSION: This study identifies a role for laminin in the initiation of coagulation and the formation of platelet-rich thrombi under shear conditions in a FXII-dependent manner.

Validation test for climate control on air-loss supports.

OBJECTIVE: To develop a simple, reproducible validation test protocol for classification of air-loss support systems. DESIGN: Simultaneous experimental measurement of moisture loss and temperature reduction at the air-loss support surface-human body equivalent interface from a sweating human skin analogue. SETTING: A hospital department of physical medicine and rehabilitation. OTHER PARTICIPANTS: These 3 manufacturers contributed 14 support surfaces. INTERVENTIONS: Test support surfaces and a standard foam mattress were placed on a hospital bed. Water was circulated to a loading gauge, placed on a dry moisture reservoir, and connected to a water bath to keep the interface at 37 degrees +/- 0.5 degrees C. The loading gauge and support surface was adjusted 23cm below the water bath level and the air flow through the interface initiated. After the dry moisture reservoir came to temperature equilibrium for 30 minutes, it was replaced with a wet one that was saturated with 36g of saline. The temperature change and evaporation rate were recorded throughout a 90-minute test period. MAIN OUTCOME MEASURES: Temperature of support surface interface and evaporation rate. RESULTS: Clustered data from temperature reduction and standardized rate of moisture loss yielded 3 groups of support surfaces in categories of no air loss (control), low air loss (LAL), and high air loss. The mean values of the characteristic temperature reduction and rate of moisture loss differed significantly between the groups. By multiple comparisons with Bonferroni's adjustment, the group means differed significantly for average temperature reduction (p <.017) and for standardized rate of moisture loss (p =.0001). The measured temperature change at any instant of time reflected the effect of evaporation and the opposing effect of thermal conductivity. CONCLUSION: Measurements of support interface climate change allowed for selective grouping of LAL surfaces according to rate of moisture evaporation and the resulting temperature reduction. Neither temperature change nor evaporation rate alone was sufficient to determine the microclimate characteristics of the support surface. Combined, these characteristics can effectively describe the performance of any LAL support system and may be used to define standards of performance.

A technique for quantifying the response of seated individuals to dynamic perturbations.

A technique is presented for monitoring the seated postural stability and control of human subjects. Estimates are made of the locations of the subject's center of pressure (CP(S)) and projection of the center of mass (CM(NP)) from moment balance equations using measured force and acceleration data. The CP(S) and CM(NP) indices describe the stability of the subject, independent of the chair, even in the presence of perturbations. The measurement system was evaluated for both rigid objects and human subjects situated in a wheelchair undergoing displacement. Estimated CM(NP) was within +/-5 mm of the actual value for static loads. For human subjects, the average correlation coefficient between the estimated CM(NP) signal and that computed from video data was 0.90; however, transient overestimation of displacement was seen during subject acceleration. The technique could help to better assess seated stability in dynamic environments, such as those experienced by wheelchair users in motor vehicles.

Bonding the gap between petralit and ceromers: with case reviews.

The search for a metal-free, aesthetic restoration with optimal strength, longevity, and comfort easily dates back to the 19th century. However, the popularity of adhesively retained restorations has reached an all-time high due to improvements in wear, post-op sensitivity, bond material and strength, and aesthetic quality. Targis/Vectris, a ceromer restorative material introduced in 1997 by Ivoclar-Williams, is a ceramic optimized polymer that produces a strong fiber-reinforced tooth-colored restoration. It allows the clinician to fabricate metal-free restorations without the fracture potential seen with ceramic materials. Long-term longitudinal studies of this restorative material will be the litmus test, but we now have 10-year studies that show very promising results.

A low-cost, portable system for the assessment of the postural response of wheelchair users to perturbations.

Maintaining seated postural stability presents a serious challenge to wheelchair users in vehicles, even during normal driving conditions. The purpose of this research was to develop a system for the study of seated postural control in response to perturbations similar to those that might be experienced during vehicle turning and braking. A servo-controlled tilt platform was constructed to provide a low-cost, small, and easily transportable device for generating precise and repeatable perturbations. Tilt platform operation was examined for accuracy and reproducibility of a desired perturbation. Repeatability was high with a mean signal-to-noise ratio (SNR) of 45.4 for a given perturbation measured across 11 subjects. An initial comparison of stability results obtained on the tilt platform and in a vehicle showed a correspondence, although differences were apparent. The tilt platform has been used successfully to assess balance in spinal cord-injured subjects and to test wheelchair securement systems.

Synthesis and antimuscarinic properties of some N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones.

In a study aimed toward developing new, selective antimuscarinic drugs with potential utility in the treatment of urinary incontinence associated with bladder muscle instability, a series of N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones, conformationally-constrained lactone relatives of benactyzine, was prepared. The compounds were examined in several paradigms that measure muscarinic (M1, M2, and M3) receptor antagonist activity. Selected members of the series that displayed potency and/or selectivity in these tests were studied for their effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. These studies revealed that incorporation of the amino functionality into an imidazole or pyrazole ring resulted in some novel, potent, and selective antimuscarinic agents. Appropriate alkyl substitution of position 2 of the imidazole strikingly affected muscarinic, particularly M3, receptor activity and may reflect a complementary site of interaction. Some of the compounds selectively reduced bladder pressure in a cystometrogram (CMG) model without producing concomitant mydriatic and salivary effects. The separate and distinct action of several compounds of this series in these in vivo protocols suggests the possibility of subtypes of muscarinic receptors that may correspond to previously characterized molecular cloned subpopulations. In this article, structure-activity relationships for the series of substituted lactones are discussed. These studies led to the identification of (R)-[(2-isopropyl-1H-imidazol-1-yl)methyl]-4,5-dihydro-3,3-diphenyl-2(3H )- furanone (23) as a clinical candidate for treating urinary bladder dysfunction.

Aminoalkynyldithianes. A new class of calcium channel blockers.

Several dithiane derivatives, prepared as intermediates for compounds structurally related to the therapeutically useful antimuscarinic agent oxybutynin, were effective inhibitors of calcium ion induced contraction of guinea pig ileal strips and of KCl-induced calcium entry into neuronal cells. Although the first member of this series, 2-[5-(diethylamino)-3-pentynyl]-1,3-dithiane (2a), was only marginally effective, its condensation product with diphenyl ketone, i.e. 2-[5-(diethylamino)-3-pentynyl]-2-(a,a-diphenyl-a- hydroxymethyl)-1,3-dithiane (3a), demonstrated weak, but significant, calcium channel antagonist activity. As part of a structure-activity relationship (SAR) study, various structural analogues of 2a and 3a were prepared and examined for calcium antagonist properties. In addition to these structural types, ring bridged (tricyclic) congeners of 3, i.e. 4, related bicyclic compounds 5, dehydroxylated derivatives 6, some homologous 2-[[[(N,N-disubstituted-amino)methyl]2- phenyl-1,3-dithianes (7), and a series of 2-[6-[N,N-disubstituted-amino)methyl]-1-hydroxy-1-phenyl- 4-hexynyl]-1,3-dithianes (8) were prepared and studied for calcium channel blocking activity. In general, greatest potency was noted in the tricyclic series 4; however, a definitive SAR could not be established. A structural similarity between several potent calcium antagonists having the structures 7c, 8b, and 8d and the well-known calcium channel blockers verapamil and tiapamil suggests these compounds may act at the same site. Compounds in the other classes (2-6) failed to show clearly defined SAR and their potency differed markedly in two tests for calcium channel antagonist activity. These results may indicate that the dithiane derivatives 2-6 produce their effects in a manner differing from that of the calcium channel antagonists diltiazem, verapamil, and nitrendepine.

A symmetrical 1,4-dihydropyridine with opposite actions on K(+)-induced contractions in guinea-pig ileum.

The effects of 1,4-dihydro-2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid dimethyl ester (DHMP) on Ca2(+)-evoked contractions in potassium-depolarized guinea-pig ileum longitudinal muscle were evaluated. DHMP (1-10 nM) potentiated Ca2(+)-evoked contractions; maximum enhancement was seen at 1 nM. A concentration-dependent inhibition of Ca2(+)-induced contractility was observed at higher concentrations. Racemic BAY K 8644 (1 nM - 1 microM), on the other hand, enhanced ileum responses to Ca2+ with a maximum effect at 3 nM. BAY K 8644, but not DHMP, directly elicited concentration-dependent contractions. The results provide further support for the hypothesis that dihydropyridines can act as both Ca2+ agonists and antagonists.

Transient solute diffusion in articular cartilage.

The one-dimensional transient diffusion of glucose, inulin and dextran into adult bovine knee articular cartilage was determined for transport times of 1, 5, 15 and 60 min, and 4, 12, 24 and 48 h. The apparent diffusion coefficient and apparent interface partition coefficient were calculated from the concentration-depth profiles within the tissue using a theoretical model for non-steady state solute diffusion. The diffusion coefficient was found to decrease with both solute size and transport time. The partition coefficient also decreased with solute size but increased with transport time. Neither coefficient was dependent on normal tissue fluid or proteoglycan content variations.

Characteristics of state prisoners who demonstrate severe adjustment problems.

Hypothesis was tested that prison inmates who present serious disciplinary problems during incarceration that result in human injury, threat to personal safety, or extensive property damage also will tend to show a history of significant societal maladjustment as compared to prisoners who do not demonstrate adjustment problems. Societal maladjustment was defined to include significant problems in education, marriage, military service, and job stability. This project was an effort to present a picture of the types individuals who cause what generally are considered to be the more severe prison disturbances. The social and relevant background areas were investigated of 50 male state prison inmates who had committed serious acting-out infractions. The same background data were checked on 50 inmates who demonstrated good prison adjustment within the same time period. When background data were analyzed carefully, a trend was discovered that indicated that prisoners who create serious trouble while confined also tend to have significant histories of social failures. The results are interpreted as in favor of the hypothesis.